archives of academic emergency medicine. 2021; 9(1): e38 https://doi.org/10.22037/aaem.v9i1.1148 le t t e r to ed i to r tactile method in confirming proper endotracheal intubation in emergency setting; a letter to editor behrang rezvani kakhki1, mohsen miri1, morteza talebi doluee1, zeynab sabeti baygi2, zahra abbasi shaye3, elnaz vafadar moradi1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical science, mashhad, iran. 2. department of obstetrics and gynaecology, faculty of medicine, mashhad university of medical science, mashhad, iran. 3. clinical research development unit, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: april 2021; accepted: april 2021; published online: 9 may 2021 cite this article as: rezvani kakhki b, miri m, talebi doluee m, sabeti baygi z, abbasi shaye z, vafadar moradi e. tactile method in confirming proper endotracheal intubation in emergency setting; a letter to editor. arch acad emerg med. 2021; 9(1): e38. dear editor, orotracheal intubation is one of the sure ways to manage airways in critical patients (1, 2). failed intubation (failure to properly place the endotracheal tube (ett) in trachea) is a rather common event (3). there have been many techniques to confirm proper intubation, but none of them are applicable in all conditions. methods such as capnography, tracheal sonography and chest-x-ray, were introduced for verification of proper tracheal intubation but they have their own limitations (4, 5). given the significance of proper airway management, the authors focused on a secondary method of verifying proper intubation using tracheal tactile method and compared it to existing methods. this cross-sectional study was conducted on patients in need of intubation at emergency departments of emam reza, ghaem, and hasheminejad hospitals of mashhad, iran. patients with abnormal airway anatomies, cardiopulmonary arrest, severe cervical trauma, and tracheal or endobronchial traumas with increased risk of aspiration were excluded. ethics committee of mashhad university of medical sciences approved the protocol of this study (ethics code: ir.mums.fm.rec.1395.644). orotracheal intubation was performed for all participants and at the same time a welltrained expert (resident) touched the trachea (thumb and index finger on both sides of the trachea under the adam’s apple) without applying any pressure. when the tube was inserted, he/she would tell whether he/she thought the tube was properly placed. other than tactile method, capnog∗corresponding author: elnaz vafadar moradi; department of emergency medicine, faculty of medicine, mashhad university of medical science, mashhad, iran. email: vafadarme@mums.ac.ir, tel: +989151178625.orcid: https://orcid.org/0000-0001-9579-7451 raphy, chest auscultation, and chest-x-ray (all 3 measures) were performed for confirmation of ett placement (as gold standard) in all cases. cases in which 2 out of 3 methods, one of which was always capnography, confirmed the proper location of ett, were considered as proper intubation. finally, 181 patients with mean age of 71.2 ± 16 years were studied (58.8% male). based on the tactile method, in 161 (89%) cases, the tube had passed into the trachea. however, other methods confirmed proper intubation in 171 (94.5%) cases. sensitivity, specificity, and positive and negative predictive values of tactile method in confirmation of proper placement of endotracheal tube were 93% (95% ci: 88%95%), 80% (95% ci: 76%-83%)), 98.7% (95% ci: 96%-100%), and 40% (95% ci: 38%-44%), respectively. in addition, positive and negative likelihood ratios of tactile method in this regard were 4.65 and 0.087, respectively. with the tactile method, it was observed that there were 159 cases of true positive and 12 cases of false positive, which could be due to shortage of time and poor technical skills due to little experience in the tested method. it seems that, the method may perform much better with more time and practice. our results support the results of gamble et al. performed on 50 children between 2 and 10 years old, who were divided into 3 groups based on tactile confirmation of ett placement through their suprasternal notch (6). eventually, they concluded that the tactile method provided better clinical results than pediatric advanced life support (pals) formula in guiding intubation. mckay et al. studied 77 people and observed that tactile ett tube placement confirmation via the suprasternal notch was easy or relatively easy in 60 cases, and hard or impossible in 17. they concluded that higher age, diabetes and smoking were associated with rigidity in tracheal rings, which prevents a good sense of touch on the intubation site (7). their this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rezvani kakhki et al. 2 results match those of the present study with one difference; the effects of underlying factors on verification of tracheal intubation were not evaluated in the present study, but will hopefully be the subject of future studies. according to the authors’ findings, it could be concluded that the tactile technique is a quick, inexpensive, accurate and risk-free technique to verify proper ett placement without any need for special equipment or skills. 1. declarations 1.1. acknowledgment the authors would like to express their sincerest appreciations for cooperation and contributions of ghaem, emam reza, and heshemi nezhad hospitals in mashhad, operating under supervision of research department of mashhad university of medical sciences. 1.2. authors’ contributions study concept and design: brk, mm acquisition of the data: mm, mtd, zas analysis and interpretation of the data: zas, evm drafting of the manuscript: evm critical revision of the manuscript for important intellectual content: all the authors statistical expertise: zsb acquisition of funding: evm, brk 1.3. conflicts of interest there was no conflict of interest in this study. 1.4. funding support none. references 1. ahmadi k pe, ramezani m, ebrahimi m. sonography as a secondary technique for confirming the location of the tracheal. journal of mashhad university of medical sciences. 2014:236-42. 2. abbasi s fd, zare m.a, hajimohammadi m, rezai m, hafezimoghadam p. direct ultrasound methods: a confirmatory technique for proper endotracheal intubation in the emergency department. european journal of emergency medicine. 2015;22(1):10-6. 3. park sc rh, yeom sr, jeong jw, cho sj. confirmation of endotracheal intubation by combined ultrasonographic methods in the emergency department. . emerg med australas. 2009;21:293-7. 4. weaver b lm, blaivas m. confirmation of endotracheal tube placement after intubation using the ultrasound sliding lung sign. academic emergency medicine. 2006;13:239-44. 5. sitzwohl ch la, schober a, krafft p, sessler d, et al. endobronchial intubation detected by insertion depth of endotracheal tube, bilateral auscultation, or observation of chest movements: randomised trial. bmj. 2010;5943:341. 6. gamble j. j mwp, wang a. f, yip k. a, o’brien j. m, plewes c. e. three-finger tracheal palpation to guide endotracheal tube depth in children. . paediatr anaesth. 2014;24(0):1050-55. 7. mckay w.p kj, pelivanov v, o’brien j.m, plewes ch. tracheal palpation to assess endotracheal tube depth: an exploratory study. . j can anesth. 2014;61:229-34. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2021; 9(1): e12 https://doi.org/10.22037/aaem.v9i1.1068 le t t e r to ed i to r video-laryngoscopy-assisted fishbone removal from the upper digestive tract; a letter to the editor petros v. vlastarakos1∗, konstantinos chondrogiannis2 1. ent department, mitera infirmary, athens, greece. 2. anaesthesiology department, mitera infirmary, athens, greece. received: december 2020; accepted: december 2020; published online: 5 january 2021 cite this article as: v. vlastarakos p, chondrogiannis k. video-laryngoscopy-assisted fishbone removal from the upper digestive tract; a letter to the editor. arch acad emerg med. 2021; 9(1): e12. dear editor, fish bones are frequently lodged in the upper digestive tract, usually at the palatine tonsils, tongue base, valleculae, and pyriform sinuses. the otorhinolaryngologist represents the first point of contact in such cases, which may in fact account for a sizeable percentage of ent emergencies (1). persistent sharp pain in the throat, experienced by the patient following eating fish, indicates that a fishbone has stuck. if the bone is not removed in a timely manner, it may result in serious septic complications (2). fishbone removal requires dexterity on the part of the ent surgeon and co-operation on the part of the patient. removal of fishbones in the oro-pharynx or base of tongue is usually easy; bones lodged further down may require a threehand technique, i.e. the patient or an assistant holding the tongue, and not infrequently, turn out to be an intolerable task in the outpatient setting. we have succeeded in managing such cases under general anaesthesia without intubation, with the use of a rigid anaesthetic video-laryngoscope and a pair of magill forceps. placed in supine position, the patient is pre-oxygenated. induction to anesthesia with propofol and remifentanil is followed by ventilation. the anaesthetist elevates the vallecular aspect of the epiglottis, using a blade with a steep curved bend for alignment of the oral, pharyngeal, and laryngeal axes, to fully expose and visualize the glottis and adjacent areas of the hypopharynx. with the video image projected from the distal end of the laryngoscope blade, the ent surgeon advances the magill forceps (or any rigid instrument felt appropriate) until the fishbone is grasped. the bone is ∗corresponding author: petros v. vlastarakos; 6 erythrou stavrou street, marousi-athens, greece. postal code: 15123, e-mail: pevlast@hotmail.com, tel: 00302114085386, mobile: 00306977803852, fax number: 00302106869161, orcid: https://orcid.org/0000-0002-2803-1971. subsequently removed with a slight rotating movement. the two-dimensional visualization of a three-dimensional area and the need to interrupt for ventilation, require communication and co-ordination between the anaesthetist and the ent surgeon, but the respective learning curve is fairly short. the advantages include good illumination, clear visualization, and precise extraction (3). the technique itself is efficient, safe, well tolerated, and with low morbidity, being analogous with the concept of the “four hands technique” employed in various endoscopic surgeries (4). despite the limited indication, this method may reduce limitations associated with non-invasive fishbone removal, the ingestion of which would most likely continue to accompany the eating habits of human societies. 1. declarations 1.1. conflicts of interest none declared. 1.2. funding the authors have no financial interest and have not received any financial support for this article. 1.3. ethical approval all procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 helsinki declaration and its later amendments. the patients signed a consent form regarding the publication of intra-operative photographs for educational or other purposes. 1.4. authors’ contributions drs. vlastarakos and chondrogiannis contributed on constructing an idea or hypothesis for research and/or manuscript; planning methodology to reach the conclusion; this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. v. vlastarakos and k. chondrogiannis 2 figure 1: a: the dorsal fin of a cod horizontally lodged in the area of the pyriform sinuses. b: fishbone grasped with a pair of magill forceps under video-laryngoscopic guidance (different case than figure 1). c: 3cm fishbone removed en-bloc from the hypopharynx via the videolaryngoscopy-assisted technique. organizing and supervising the course of the project or the article and taking the responsibility; providing personnel, environmental and financial support and tools and instruments that are vital for the project; taking responsibility in logical interpretation and presentation of the results; taking responsibility in this necessary function; taking responsibility in the construction of the whole or body of the manuscript; reviewing the article before submission not only for spelling and grammar but also for its intellectual content. references 1. ray r, dutta m, mukherjee m, gayen gc. foreign body in ear, nose and throat: experience in a tertiary hospital. indian journal of otolaryngology and head & neck surgery. 2014;66:13-6. 2. ahmad ra, ishlah w, shaharudin m, sathananthar k, norie a. posterior mediastinal abscess secondary to esophageal perforation following fish bone ingestion. the medical journal of malaysia. 2008;63:162-3. 3. swain s, pani s, sahu m. management of fish bone impaction in throat – our experiences in a tertiary care hospital of eastern india. egyptian journal of ear, nose, throat and allied sciences. 2016;18:27-30. 4. sakaida h, chiyonobu k, ishinaga h, takeuchi k. use of a rigid curved laryngoscope for removal of a fish bone in the hypopharynx. case reports in otolaryngology. 2016;2016:1-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2022; 10(1): e20 or i g i n a l re s e a rc h skin cooling to reduce the pain associated with local anesthetic injection; a randomized controlled trial saeed majidinejad1, farhad heidari1, amirhosein famil chitgarian1∗ 1. department of emergency medicine, isfahan university of medical sciences, isfahan, iran. received: january 2022; accepted: february 2022; published online: 10 march 2022 abstract: introduction: different methods have been proposed for the reduction of the pain caused by the injection of local anesthetics. this study aimed to evaluate the effect of skin cooling on reduction of pain associated with local injection of lidocaine buffered with sodium bicarbonate. methods: this randomized controlled trial included 108 adult patients with arm/forearm wounds who referred to the emergency departments. participants were randomly allocated to two equal groups. patients in both groups received subcutaneous injection of buffered lidocaine. in the intervention group, an ice cube measuring 2 × 2 × 2 cm (at 0 ◦ c) in sterile gloves was placed on the wound for 2 minutes before the injection of buffered lidocaine. the primary outcome was severity of pain during lidocaine injection using a visual analog scale (vas). results: one hundred and eight patients were enrolled in the study, 54 in each group. there was no statistically significant difference in age (p = 0.777), sex (p = 0.466), and length of laceration (p = 0.410) between the two groups. the pain scores during lidocaine injection were significantly lower in the intervention group compared to control group (2.39 ± 1.14 vs 4.26 ± 0.94, p < 0.001). conclusion: skin cooling prior to the injection of local anesthetics can significantly reduce the pain caused by local anesthetic infiltration keywords: lidocaine; wounds and injuries; injections; anesthesia, local; pain; emergency service, hospital cite this article as: majidinejad s, heidari f, famil chitgarian a. skin cooling to reduce the pain associated with local anesthetic injection; a randomized controlled trial. arch acad emerg med. 2022; 10(1): e20. https://doi.org/10.22037/aaem.v10i1.1562. 1. introduction primary repair of wounds is usually performed in the emergency department (ed). wounds of arms/forearms can occur frequently since the upper extremities are quite often used to ward off serious injuries. the skin of arm/forearm is thin, with densely distributed nociceptors resulting in the lower threshold of pain in these areas; therefore, even uncomplicated surgical procedures such as suturing of simple lacerations may require subcutaneous injection of local anesthetics (1, 2). lidocaine, as the most popular anesthetic agent, is used to alleviate procedural pain, but paradoxically it can cause pain or discomfort during subcutaneous injection (3-5). for patients undergoing minor surgery such as wound repair, it is often the lidocaine injection that is the most painful part of procedure (2, 3). administration of local anesthesia for wound re∗corresponding author: amirhosein famil chitgarian; department of emergency medicine, isfahan university of medical sciences, isfahan, iran. email: amirchitgarian@gmail.com, tel: 00989185479835, orcid: http://orcid.org/0000-0002-3687-7176. pair appears to be the seventh most uncomfortable ed procedure (2). various methods have been used for relieving the pain caused by local anesthetics injection in previous studies, including warming lidocaine or mixing it with sodium bicarbonate (3). buffering with sodium bicarbonate or warming will reduce the shelf life of lidocaine from 14 to 7 days, requiring additional equipment for storage (2, 3). cooling has been used for analgesia and pain management (6). ice cubes and cooling sprays have been reported to effectively reduce the pain caused by arterial or venous punctures (7, 8). pain alleviation for bruises, fractures, bites, sports injuries, sprains, and burns has been achieved with this technique as well (9). cryotherapy has also been demonstrated to be effective for postoperative pain management when applied preoperatively (10, 11). pre-cooling for pain reduction in dental procedures is also well described (12). preemptive cryotherapy for relieving the pain caused by subcutaneous injection of lidocaine for the repair of simple lacerations has shown to be effective in wounds occurring in different parts of the body, including upper and lower extremities, trunk, and face (2). this study aimed to evaluate the effectiveness of skin cooling on the reduction of pain assothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. majidinejad et al. 2 ciated with local injection of lidocaine buffered with sodium bicarbonate. 2. methods 2.1. study design and setting this prospective randomized controlled trial was conducted in the emergency department (ed) of alzahra and kashani hospitals in isfahan, iran, in 2021. the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1398.278) approved the study protocol and it complies with the statements of the declaration of helsinki. the trial was registered in the iranian registry of clinical trials under the number irct20180129038549n14. all patients provided written informed consent for participation in the study. 2.2. participants all adult patients with acute arm/forearm wounds referred to the ed were enrolled in the study. inclusion criteria were 1870 years of age, superficial wound/laceration of arm/forearm (a laceration not involving the fascia or muscle and requiring a one-layer suture), wound surface area ≤5 cm2, being alert, and willing to participate in the study. patients with visual, mental, or verbal disorders, multiple trauma, unstable vital sign, a history of peripheral neuropathy, and a history of an allergic reaction to local anesthetics were excluded. patients experiencing agitation or irritability caused by cooling during the study were also excluded. 2.3. interventions then patients were divided into two equal groups (intervention group and control group) using the random allocation software and simple random sampling method. in the intervention group, an ice cube measuring 2 × 2 × 2 cm (at 0 ◦ c) in sterile gloves was placed on the wound for 2 minutes and then buffered lidocaine injection was performed. in the control group, no ice cube was used before injecting buffered lidocaine. patients in both groups received approximately 10 ml of buffered lidocaine that were fitted with 27-guage needles. 1% lidocaine hydrochloride mixed with 8.4% sodium bicarbonate with a ratio of 9 to 1 was used for this study. since the buffered solution has increased ph, its half-life in room temperature decreases; therefore, the solution was made right before the injection. the buffered lidocaine was injected by an assistant who was blinded to the allocation. immediately after injection, each patient was asked to rate the pain using the visual analogue scale (vas) from 0 to 10 by marking a vertical line (0: no pain, 10: the worst possible pain imaginable). in the beginning of the study, patient characteristics (age and sex) and length of the laceration were recorded. all measurements and data gathering were performed by investigators blinded to randomization. 2.4. data analysis the statistical package for the social sciences (spss) software (version 25.0, armonk, ny: ibm corp.) was used for data analysis. mean, standard deviation, frequency, and percentages were used to describe the results. the chi-squared test was used to compare sex distribution between groups. independent t-test was used to compare age and pain scores between groups. p-values ≤0.05 were regarded as statistically significant. the sample size was determined as at least 54 participants in each group using the formula for comparison of two means with α=0.05, β=0.2, δ1=3.5, δ2=7, µ1=2, and µ2=5 based on the mean of pain scores in two groups form the study by song et al. (2). 3. results a total of 198 patients were evaluated, 108 of whom were included in the analysis; 54 patients in the intervention group, and 54 patients in the control group (figure 1). the mean age was 43.95±13.14 (19-68 years) years (80.6% male). there was no statistically significant difference regarding age (p = 0.777), sex (p = 0.466) and length of laceration (p = 0.410) between the two groups (table 1). the pain scores during lidocaine injection were significantly lower in the intervention group compared to control group (2.39 ± 1.14 vs 4.26 ± 0.94, p < 0.001). no wound complications occurred in either group. shivering was observed in 2 patients in the intervention group who did not need treatment. 4. discussion based on the findings of the present study; skin cooling prior to the injection of local anesthetics can significantly reduce the pain caused by local anesthetic infiltration. local anesthetic injection is regarded as one of the most painful components of minor procedures such as superficial wound repair (2-4). the health care providers’ efforts to effectively control pain have been associated with improved patient outcomes, and it is important to find strategies to reduce all pain-related elements of the procedure (13). pain and anxiety are thought to prevent some patients from receiving any care, including local anesthetic injections (11). there are several factors that can reduce the pain caused by the anesthesia itself and increase patient satisfaction, including selection of the most appropriate solution, proper preparation of the solution, careful selection of the required equipment, preparation of the site of injection, and procedural techniques (14). this study demonstrated that local pre-cooling with ice cube this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e20 table 1: comparing the baseline characteristics of studied cases between groups variables skin cooling (n=54) control (n=54) p-value sex male 42 (77.8) 45 (83.3) 0.466 female 12 (22.2) 9 (16.7) age (years) mean ± sd 44.31 ± 12.97 43.59 ± 13.41 0.777 laceration size (cm) mean ± sd 3.72 ± 0.25 3.95 ± 0.33 0.410 pain severity* mean ± sd 2.39 ± 1.14 4.26 ± 0.94 <0.001 data are presented as mean ± standard deviation or frequency (%). *based on vas, visual analogue scale. figure 1: consort flow diagram of the study. can significantly reduce the pain associated with local anesthetic injection. similarly, song et al. showed that the median of subjective numeric rating (0-10 scale) was significantly lower in the cryotherapy group compared to the control group (2). their study was comparable with ours in many aspects including the purpose of local anesthetic injection, the tool used for evaluation of the perceived pain, and the type of local anesthetic. nevertheless, they assessed the efthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. majidinejad et al. 4 fect of pre-cooling on local anesthetic injection pain at different sites while we only included patients with arm/forearm wounds. mahshidfar et al., in their study on patients with superficial lacerations, showed that cooling the injection site prior to local anesthetic injection can significantly reduce the pain and discomfort caused by the injection (5). their results are consistent with the results of the present study. soft tissue cooling has also been found to help decrease pain during injection of local anesthetics in children for dental procedures (15). furthermore, cryotherapy has been shown to be effective for pain reduction in many surgical fields including obstetrics, ophthalmology, orthopedics, otorhinolaryngology, and plastic surgery (9-11). a previous study showed that cryo-analgesia with ice cubes was effective in reducing the pain of local anesthetic infiltration for eyelid surgery (9). it is not clear exactly how cooling reduces this pain, but it is thought that vasoconstriction and reduced nerve conduction may play an important role (2, 16-19). generally, nonmyelinated c fibers and myelinated a-delta fibers are responsible for rapid transmission of pain. since pain transmission consists of a set of electrochemical reactions and all chemical reactions are slowed down at lower temperatures, nerve conduction velocity can decrease with reduced tissue temperature. in fact, signal conduction through adelta fibers stops at 10◦c (6). hence, cooling would provide analgesia by decreasing nerve conduction and increasing pain threshold (10, 16). other underlying mechanisms of cryotherapy that may contribute to pain reduction are reduced inflammation, decreased oxygen demand, limited production of free radicals, and preventing neural plasticity through reducing free nerve ending sensitivity (17, 18). 5. limitation a limitation of the current study may be the injection of buffered lidocaine instead of lidocaine alone, because adding sodium bicarbonate to lidocaine has been demonstrated to significantly reduce pain from anesthetic injection based on the belief that the acidity of lidocaine is responsible for the pain caused during its local injection (2). therefore, the application of buffered lidocaine may have decreased the true effect of pre-cooling. because of the nature of the interventions, blinding of patients was not possible. evaluation of pain severity via a subjective method (vas) can be considered as a limitation of the present study. 6. conclusion according to the results of the current study, pre-cooling approximately 2 minutes prior to the injection of the local anesthesia with lidocaine, buffered with sodium bicarbonate, in arm/forearm wounds can reduce the pain caused by injection. however, further studies with larger sample sizes are required to confirm the findings of the current study. 7. list of abbreviations • ed: emergency department • vas: visual analogue scale 8. declarations 8.1. acknowledgments we would like to express our sincere gratitude towards the personnel of the emergency departments of alzahra and kashani hospitals, isfahan, iran. 8.2. authors’ contributions s.m., f.h., and a.f.c.; contributed to conception, study design, and data collection and evaluation. f.h. and a.f.c.; contributed to statistical analysis, and interpretation of data. f.h. and a.f.c.; drafted the manuscript, which was revised by s.m.. all authors read and approved the final manuscript. 8.3. funding this study was financially supported by isfahan university of medical sciences. 8.4. competing interests the authors declare that they have no competing interests. 8.5. availability of data and materials the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. references 1. eshkevari l, trout kk, damore j. management of postpartum pain. j midwifery womens health. 2013;58(6):622-31. 2. song j, kim h, park e, ahn jh, yoon e, lampotang s, et al. pre-emptive ice cube cryotherapy for reducing pain from local anaesthetic injections for simple lacerations: a randomised controlled trial. emerg med j. 2018;35(2):103-7. 3. finsen v. reduced pain when injecting lidocaine. tidsskr nor laegeforen. 2017;137(9):629-30. 4. azizkhani r, sani ms. topical lidocaine plus diclofenac as a local anesthetic agent in central venous catheterization; a randomized controlled clinical trial. arch acad emerg med. 2021;9(1):e63. 5. mahshidfar b, shevi sc, abbasi m, kasnavieh mh, rezai m, zavereh m, et al. ice reduces needle-stick pain assothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e20 ciated with local anesthetic injection. anesth pain med. 2016;6(5):e38293. 6. trescot am. cryoanalgesia in interventional pain management. pain physician. 2003;6(3):345-60. 7. hijazi r, taylor d, richardson j. effect of topical alkane vapocoolant spray on pain with intravenous cannulation in patients in emergency departments: randomised double blind placebo controlled trial. bmj. 2009;338. 8. bastami m, azadi a, mayel m. the use of ice pack for pain associated with arterial punctures. j clin diagn res. 2015;9(8):jc07-9. 9. goel s, chang b, bhan k, el-hindy n, kolli s. “cryoanalgesic preparation” before local anaesthetic injection for lid surgery. orbit. 2006;25(2):107-10. 10. watkins aa, johnson tv, shrewsberry ab, nourparvar p, madni t, watkins cj, et al. ice packs reduce postoperative midline incision pain and narcotic use: a randomized controlled trial. j am coll surg. 2014;219(3):511-7. 11. gostimir m, hussain a. a systematic review and metaanalysis of methods for reducing local anesthetic injection pain among patients undergoing periocular surgery. ophthalmic plast reconstr surg. 2019;35(2):113-25. 12. bhadauria us, sandesh n, mishra p, godha s. effect of injection site pre-cooling on pain perception in patients attending a dental camp at life line express: a split mouth interventional study. clujul med. 2017;90(2):220. 13. patel bk, wendlandt bn, wolfe ks, patel sb, doman er, pohlman as, et al. comparison of two lidocaine administration techniques on perceived pain from bedside procedures: a randomized clinical trial. chest. 2018;154(4):773-80. 14. strazar ar, leynes pg, lalonde dh. minimizing the pain of local anesthesia injection. plast reconstr surg. 2013;132(3):675-84. 15. bose s, garg n, pathivada l, yeluri r. cooling the soft tissue and its effect on perception of pain during infiltration and block anesthesia in children undergoing dental procedures: a comparative study. j dent res dent clin dent prospects. 2019;13(3):159. 16. yoon wy, chung sp, lee hs, park ys. analgesic pretreatment for antibiotic skin test: vapocoolant spray vs ice cube. am j emerg med. 2008;26(1):59-61. 17. nadler sf, weingand k, kruse rj. the physiologic basis and clinical applications of cryotherapy and thermotherapy for the pain practitioner. pain physician. 2004;7(3):395-400. 18. muldoon j. skin cooling, pain and chronic wound healing progression. br j community nurs. 2006;11(sup1):s21-s5. 19. east ce, dorward ed, whale re, liu j. local cooling for relieving pain from perineal trauma sustained during childbirth. cochrane database syst rev. 2020;10(10):cd006304. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion list of abbreviations declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 178 emergency 2014; 2 (4): 178-179 case report essential thrombocytosis following multiple psychic traumas rezvan sadr mohammadi1, mehrdad mahdian2, reza bidaki3*, seyed-ali mostafavi4,5 1. department of clinical psychology, kar higher education institute of rafsanjan, rafsanjan, iran 2. trauma research center, kashan university of medical sciences, kashan, iran 3. department of psychology, rafsanjan university of medical sciences, rafsanjan, iran 4. psychiatry research center, roozbeh hospital, tehran university of medical sciences, tehran, iran 5. iranian petroleum industry, health research institute (ipihri), nioc central hospital, tehran, iran abstract the associations between exposure to traumatic events and psychiatric disorders such as posttraumatic stress disorder (ptsd), depression, and anxiety have been established. it is important that clinicians notice to this phenomenon and avoid from inappropriate interpretations and additional laboratory tests. here, a case of 45-year-old man with essential thrombocytosis developed after multiple psychic traumas was introduced. key words: stress disorders, post-traumatic; thrombocytosis; case management; case reports cite this article as: sadr mohammadi r, mahdian m, bidaki r, mostafavi sa. essential thrombocytosis following multiple psychic traumas. emergency. 2014;2(4):178-9. introduction: 1 ssential thrombocytosis (et) is a hematological disease that may causes venous thrombosis in different parts of the body. et was determined by abnormal megakaryocyte proliferation with a rare incidence of 2.5 to 7 per 1,000,000 population (1-3). it can be associated with both thrombosis and hemorrhage (2, 3). thrombocytosis describes with elevated platelet count above 450 × 103/mm3, which can be primary including et or secondary including iron deficiency, infection, blood loss, and malignancy (2). in previous literatures the associations between exposure to traumatic events and psychiatric disorders such as posttraumatic stress disorder (ptsd), depression, and anxiety have been established. also a relationship between depression, anxiety, stress and neurochemical functioning impairment was determined in previous studies (4). recent investigations have suggested that responses to traumatic stressors also appear to have a physiological foundation that could result in disorders of immune function and complete blood cell count. rises in leukocyte, lymphocyte and t-cell counts as well as changing in cell mediated immune system have been reported, too (5, 6). in this report a case of a 45-year-old man with et which developed after multiple psychic traumas was reported. case presentation: a 45-year-old married man, employee of agriculture faculty, referred to psychiatric emergency department after *corresponding author: reza bidaki; department of psychiatry, moradi hospital, moalem st, rafsanjan, iran. phone: +983915230081; fax: +983915230086. email: reza_bidaki@yahoo.com received: july 2014; accepted: july 2014 experiencing a stressful situation. he had a cystic mass in his right inguinal area about 6 months ago. his mother died due to ovarian cancer lasted during 24 years and his younger aunt deceased because of gastric cancer lasting for 8 years. patient’s uncle has also been treated for chronic lymphocytic leukemia (cll) since 2007. the patient was previously well until his cyst concerned as malignancy and involved in obsessions. after visiting it was found that there is a simple infectious cyst cured following appropriate antibiotic use. shortly later, he experienced headaches that were different from the previous ones; a pulsating severe headache in occipital area that was accompanied with neck muscles’ spasm and exacerbate with head movement. this headache had not responded to conventional analgesics. he didn’t have a history of joint pain, bleeding or other symptoms. he didn't use any drug in recent months. the patient was visited again (blood pressure=130/100 mmhg, pulse rate=78/minute, respiratory rate= 13/minute, temperature=36.8c◦) and serum laboratory test requested for him. the results were normal except for platelets count that was 1,150,000/µl. blood smear showed an increased megakaryocyte and normal for other type of blood cells. abdomino-pelvic ultrasonography didn’t present any additional findings. the patient’s stress exacerbated and obsessive thoughts came back in his mind again and his professional performance affected. he was constantly distracted and had problem for concentration. his physician ordered new tests again while his platelet count was unexpectedly increased to 1,630,000/µl. the patient consulted with a psychiatrist. after one session consultation and using stress reduction techniques, the symptoms gradually disappeared by means of appropriate e mailto:reza_bidaki@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 179 sadr mohammadi et al exercise and nutritional diet. bone marrow aspiration was suggested to him but he didn’t accept. discussion: thrombocytosis is usually observed in a variety of underlying conditions, which may cause an acute and temporary rise in platelets count (such as major surgery, trauma and acute hemorrhage), more persistent thrombocytosis (like chronic infection and inflammation, iron deficiency or neoplasia), or even a lifelong permanent increase in platelet count (2, 7, 8). reactive thrombocytosis is a condition that levels of thrombopoietin, il-6, other cytokines, or catecholamines would be risen (9, 10). boscarino, j. a. reported a distorted immune and neuroendocrine systems following ptsd (11). patients with positive ptsd were more likely to have abnormally high leukocyte, lymphocyte, and t-cell counts. some other studies have reported changes in complete blood cell count, profile of blood lymphocytes, leukocytes and immune system as well as increased level of inflammatory cytokines following ptsd (1113). as well glover, d. a. and et al. reported altered immune function and lymphocyte in patients following ptsd (14). morath, j. et al., also declared that chronic ptsd is associated with clinically elevated t-cells, hypersensitive immune responses, and the presence of biological markers. ptsd is consistent with a wide range of inflammatory diseases (15) one of which may be thrombocytosis. although altered lymphocyte and immune functions have been known in patients with ptsd, essential thrombocytosis is a rare phenomenon. this report has introduced an individual exposure to traumatic stress which has currently lower social support with higher rates of post-traumatic stress and associated disorders. here, the patient had multiple psychic traumas. although our case was asymptomatic, he didn’t have stable thrombocytosis and always had a platelet count more than 450,000 /µl with a rising trend. he was exposed to an emotional shock or a distressful situation that produced a significant impression, especially on the subconscious mind. the thrombocytosis may be rarely occurred following the stress of related disorders like ptsd. it is important for clinicians to notice this phenomenon and avoid from inappropriate interpretation and additional laboratory tests. acknowledgments: none conflict of interest: authors declared no conflict of interest. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. boscarino ja. posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. ann n y acad sci. 2004;1032:141-53. 2. schafer ai. thrombocytosis and thrombocythemia. blood rev. 2001;15(4):159-66. 3. vafaie m, jaseb k, ghanavat m, pedram m, rahiminia t. asymtomatic essential thrombocythemia in a child: a rare case report. int j hematol oncol stem cell res. 2013;7(2):357. 4. chrousos gp, gold pw. the concepts of stress and stress system disorders. overview of physical and behavioral homeostasis. jama. 1992;267(9):1244-52. 5. hohwu l, li j, olsen j, sorensen ti, obel c. severe maternal stress exposure due to bereavement before, during and after pregnancy and risk of overweight and obesity in young adult men: a danish national cohort study. plos one. 2014;9(5):e97490. 6. boscarino ja. diseases among men 20 years after exposure to severe stress: implications for clinical research and medical care. psychosom med. 1997;59(6):605-14. 7. ohyashiki k, akahane d, gotoh a, et al. uncontrolled thrombocytosis in polycythemia vera is a risk for thrombosis, regardless of jak2(v617f) mutational status. leukemia. 2007;21(12):2544-5. 8. vannucchi am, barbui t. thrombocytosis and thrombosis. hematology am soc hematol educ program. 2007:363-70. 9. alexandrakis mg, passam fh, perisinakis k, et al. serum proinflammatory cytokines and its relationship to clinical parameters in lung cancer patients with reactive thrombocytosis. respir med. 2002;96(8):553-8. 10. araneda m, krishnan v, hall k, kalbfleisch j, krishnaswamy g, krishnan k. reactive and clonal thrombocytosis: proinflammatory and hematopoietic cytokines and acute phase proteins. south med j. 2001;94(4):417-20. 11. boscarino ja, chang j. higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications. psychosom med. 1999;61(3):378-86. 12. gill jm, saligan l, woods s, page g. ptsd is associated with an excess of inflammatory immune activities. perspect psychiatr care. 2009;45(4):262-77. 13. wilson sn, van der kolk b, burbridge j, fisler r, kradin r. phenotype of blood lymphocytes in ptsd suggests chronic immune activation. psychosomatics. 1999;40(3):222-5. 14. glover da, steele ac, stuber ml, fahey jl. preliminary evidence for lymphocyte distribution differences at rest and after acute psychological stress in ptsd-symptomatic women. brain behav immun. 2005;19(3):243-51. 15. morath j, gola h, sommershof a, et al. the effect of trauma-focused therapy on the altered t cell distribution in individuals with ptsd: evidence from a randomized controlled trial. j psychiatr res. 2014;54:1-10. archives of academic emergency medicine. 2022; 10(1): e2 le t t e r to ed i to r advance without cut and retrograde removal of embedded fishhook; introducing a novel technique abdolghader pakniyat1, kourosh akhbari1∗, fatemeh radfar2,3 1. department of emergency medicine, kosar hospital, kurdistan university of medical sciences, sanandaj, iran. 2. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 3. emergency medicine department, shahid beheshti university of medical sciences, tehran, iran. received: november 2021; accepted: december 2021; published online: 1 january 2022 abstract: removing embedded fishhook without causing further tissue damage from the barbed nature of the hook is a challenge in emergency department (ed). the four most commonly used techniques include advance and cut, string-yank, needle cover, and retrograde removal. this study aims to describe a modified pushthrough technique without cutting the barb, namely advance without cut and retrograde removal, as an effective technique of successful removal of fishhooks. there is no risk of additional injury to patients and healthcare staff, and the technique does not need tools that are not generally readily available in eds. keywords: foreign bodies; wounds and injuries; soft tissue injuries; emergency service, hospital cite this article as: pakniyat a, akhbari k, radfar f. advance without cut and retrograde removal of embedded fishhook; introducing a novel technique. arch acad emerg med. 2022; 10(1): e2. https://doi.org/10.22037/aaem.v10i1.1403. dear editor; removing embedded fishhook without causing further tissue damage from the barbed nature of the hook is a challenge in emergency department (ed). the four most commonly used techniques include advance and cut, string-yank, needle cover, and retrograde removal (1, 2). most fishhooks are embedded in the skin and cutaneous soft tissue of hand, foot, and face. there are no absolute contraindications to fishhook removal. while the external injury often seems minimal, internal injuries can be dangerous, particularly when the barbed hook is lodged near a blood vessel, tendon, or nerve. surgical consultation may be obtained for appropriate removal and repair (3). the choice of removal technique is different and depends on anatomical location of the affected body part, the depth of penetration, and type and size of fishhook. xrays may aid in determining the type of fishhook and depth of penetration in difficult cases (4-6). this study presents 2 patients; a 43-year-old male and a 24year-old male with superficially embedded fishhook presenting to ed of kosar hospital, sanandaj, iran during august ∗corresponding author: kourosh akhbari; department of emergency medicine, kurdistan university of medical sciences, sanandaj, iran. tel: +98 912 339 2902, email: akhbarikourosh@gmail.com, orcid: https://orcid.org/0000-0003-3539-4129. 2021. the fishhooks were embedded in dorsal of right hand (case 1) and first and second volar of distal phalanx of left hand (case 2) with no significant hemorrhage. all sensory and motor examinations were normal. the risks and benefits of the procedure was explained to the patients initially and then push-through technique was selected for removal of fishhooks. after the skin and hook were prepped with betadine solution, in order to reduce the pain, skin overlying the point of the hook was anesthetized, either by local infiltration with 1 percent lidocaine or by digital block. after anesthesia was obtained, the shank of the hook was grasped with a hemostat and then it was advanced into the wound until the barbed end protruded through the skin. since a clean wire cutter was not available, using a needle holder, the barb was clamped and bent over body of the bend part. when the fishhooks were transformed to barbless hook, they were back out easily with no additional injury (figure 1). after washing with normal saline and dressing with antibiotic ointment, the patients were discharged with recommendations to hold the wound in warm water two to three times per day until healing is established and advised them to return if any signs of infection appear. there was no complication in the follow-up (10 days later). the advance and cut causes minimal additional soft tissue trauma and is most effective. in this technique, after the advancement of fishhook into the wound until the barb this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. pakniyat et al. 2 figure 1: a: the shank of the hook is grasped with a hemostat and then it is advanced into the wound until the barbed end protrudes through the skin; b: using a needle holder the barb is clamped and bent over the body of the bend part (made barbless); c: the hook is then removed in a retrograde manner. reemerges from the skin, the barb is cut off with a wire cutter and the remainder of the hook is then backed out of the wound. cutting the barb requires taking precautions to avoid inadvertent injury from the barb, so the patient, clinician, and other care providers in the room should wear protective eye gear (1, 2, 7, 8). in advance without cut and retrograde method, removal of the fishhook is done using medical devices like needle holder or hemostat and we do not need any tools that are not available in eds, like wire cutter. before retrograding the hook, it is recommended to make sure that the barb is bent and the fishhook is made completely barbless. the procedure must be stopped if the physician feels significant resistance when pulling the hook, which may be due to incomplete bending of the barb, as additional tissue injury and pain can be presumed. 1. declarations 1.1. acknowledgment we would like to thank dr. sepideh moradkhani for her support during the initial write up and drawing the picture of this paper. 1.2. authors’ contributions study concept and design of the manuscript: a.p; drafting, analysis, and interpretation of data: a.p, k.a and f.r; critical revision of the manuscript for important intellectual content: a.p, k.a and f.r; study supervision: a.p. 1.3. financial disclosure we had no financial interests related to the materials in the manuscript. 1.4. funding support none declared. references 1. daniel b. stone djs. foreign body removal. in: roberts jr hj, editor. roberts and hedges’ clinical procedures in emergency medicine and acute care, 7ed. philadelphia, pa: w.b. saunders; 2019 2. lammers r, mastenbrook j. soft tissue foreign bodies. in: tintinalli je, ma oj, yealy dm, meckler gd, stapczynski js, cline dm, et al., editors. tintinalli’s emergency medicine: a comprehensive study guide, 9e. new york, ny: mcgraw-hill education; 2020. 3. beasley k, ouellette l, bush c, emery m, wigstadt s, ambrose l, et al. experience with various techniques for fishhook removal in the emergency department. the american journal of emergency medicine. 2019;37(5):979-80. 4. gammons mg, jackson e. fishhook removal. american family physician. 2001;63(11):2231-6. 5. scott pm. removing a fishhook. journal of the american academy of physician assistants. 2003;16(4):69-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e2 6. thommasen hv, thommasen a. the occasional removal of an embedded fish hook. canadian journal of rural medicine 2005;10(4):254-9. 7. fish hook removal techniques [internet]. uptodate. 2021. available from: https://www.uptodate.com/contents/fish-hookremoval-techniques. 8. julian e, mammino j. don’t get hung up on fishhooks: a guide to fishhook removal. cutis. 2016;97(3):195-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 183 emergency 2014; 2 (4): 183-185 case report spontaneous spinal epidural hematoma; a case report maryam motamedi1, alireza baratloo1, alireza majidi1, farhad rahmati1*, ali shahrami2 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran abstract spontaneous spinal epidural hematoma (sshe) is a rare entity can have several reasons. its prevalence in population is 0.1 per 100,000 with the male to female ratio of 1/4:1. for the first time jackson in 1869 reported a case of sshe and after that, it was declared as several hundred cases in literatures. here, a case of sshe was reported in a 52-year-old male referred to emergency department following severe low back pain. key words: hematoma, epidural, spinal; back pain; case reports cite this article as: motamedi m, baratloo a, majidi a, rahmati f, shahrami a. spontaneous spinal epidural hematoma; a case report. emergency. 2014; 2(4):183-5. introduction: 1 pontaneous spinal epidural hematoma (sshe) is a rare entity can have several reasons. for the first time jackson in 1869 reported a case of sshe and after that, it was declared as several hundred cases in literatures. its prevalence in population is 0.1 per 100,000 with the male to female ratio of 1.4:1. sshe is rare among children and no sexual preference was seen from fetus to 14 years-old (1). based on the severity of neurologic deficits two therapeutic approaches, conservative and surgical, have been suggested. here, a case of sshe was reported in a 52-year-old male referred to emergency department following severe low back pain. case report: a 52 year-old male was admitted to the emergency department (ed) with chief complaint of low back pain. the pain began two hours prior to admission. the patient was unable to walk because of severe pain; the severity of pain based on numeric rating scale (nrs) was 10. he stated that his pain has suddenly initiated from two hours before referring and the pain severity in the early was the half of intensity of his current pain. he tried to relieve his pain at home by using drugs like muscle relaxants and non-steroidal anti-inflammatory drugs (nsaids), nevertheless due to increasing the pain he was referred to the ed. the patient did not have a serious trauma history and just mentioned that he jumped from a chair with 40 centimeters height in the previous day, without any hurt in his back or knees. the subject did not have any positive past medical history except a suspicious non-documented history of ischemic heart disease. *corresponding author: farhad rahmati; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel/fax: +98212272115; email: f.rahmati2000@yahoo.com received: july 2014; accepted: august 2014 he has not had any heart problem since that time but has been continuously taking 80 mg aspirin daily. the subject has had the history of smoking and snuff opium since many years ago. on admission to the ed, he had oral temperature of 36.5°c, 19/minute respiratory rate, 85/minute pulse rate, and 130/85 mmhg blood pressure; and 96% oxygen saturation on room air. in physical examination, he did not have tenderness in the spinal column while it presented in left buttock and left inguinal ligament. his pain had diffuse nature toward knees while the knees examination was normal. the patient kept his hip and knees in flexion position, as antalgic. the sensory and motor examination as well as deep tendon reflexes were normal. on laboratory tests, white blood cell (wbc) =12000/ µl, platelet count =224000/ µl, hemoglobin =14.7 mg/dl, sodium=139 meq/l, potassium=4.3 meq/l, blood sugar=120 mg/dl, erythrocyte sedimentation rate (esr) = 10 millimeter/hour, prothrombin time (pt) = 13.6 seconds, partial thromboplastin time (ptt) = 33 seconds, and international normalized ratio (inr) = 1.1 were reported. urinalysis was normal. although the treatment of the patient was initiated with an appropriate dose of venous analgesic agent, he did not show an affected response to the treatment and after a short time, the pain began again with the same intensity. in fact, noticing to the history of opium consumption by the patient, it was thought that maybe he wanted to exaggerate his pain to receive more opium. because of tenderness in the inguinal region, the possibility of renal stone was also assumed that rule outed by doing abdomino-pelvic computerized tomography (ct) scan without contrast. therefore, it was planned to do lumbosacral mri for the patient. the radiologist reported a small epidural hematoma in the l1/l2 regions, as shown in figures 1. immediately a neurosurgical consultant was requested and the patient with sseh diagnosis hospitalized in the neuros this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 184 motamedi et al surgery ward. the patient’s pain was controlled by a pain specialist and then he underwent conservative treatment there. finally, the patient was discharged from the hospital without surgery and any neurologic deficit after six days. discussion: patients with back pain are the common referrals to the ed and consist of 2.3% of all physician visits. in addition, 84% of adults experience the back pain in their life (2-4). some important elements in the history and physical examination can differentiate serious reasons of the back pain. the important point in this case was the presence of severe pain resistant to the treatment, which was not mentioned as red flags. sshe is an idiopathic aggregation of blood in epidural space which can be as acute, chronic, spontaneously, post traumatic, or iatrogenic (5). sseh concludes less than one percent of space occupied lesions; its pathogenesis is still unknown but believed that bleeding has a venous origin because the lack of valves in the epidural network disposes the intrinsic change in pressure. albeit in terms of recent theories, it is supposed that arterial bleeding causes to traction and mechanic disruptions on nerve roots and in some studies, it was attributed to the spontaneous rupture of an arteriovenous malformation. miyagi et al. declared that because the pressure of in t2 weighted axial cut t2 weighted sagittal cut t2 weighted coronal cut t1 weighted sagittal image figure 2: lombo-sacrale magnetic resonance imaging (mri) of patients without contrast this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 185 emergency 2014; 2 (4): 183-185 travenous network is lesser than epidural space, arterial bleeding is more possible for that (6). totally, epidural hematoma is along with a series of underlying diseases and predisposing factors such as organic vascular disease, hemodialysis, coagulation disorders, hemophilia b, thrombolysis for myocardial infarct, factor ix deficiency, long term aspirin using, and vascular malformations as well as vertebral hemangiomas; liver disease, alcoholism, and thrombocytopenia (7). the patient usually refers with a sudden sharp and radicular low back pain. the pain maybe exacerbated by percussion on the spine or with maneuvers that increase the intraspinal pressure like coughing and sneezing. the sensory and motor findings of the patient depend on the lesion site and hematoma size which can include weakness, paresis, bladder dysfunction, and sensory deficit (8). the spinal epidural hematoma is one of the potentially reversible pressure lesions on the spinal cord and roots, thus its diagnosis and treatment have a vital importance (5). presently magnetic resonance imaging (mri) is considered as the first diagnostic method of choice, which can show a biconvex hematoma in the epidural space with well-defined borders that taper towards up and down. in case of lacking mri, computed tomography scan could be used (9, 10). the initial surgical intervention is a general treatment for sseh (9). if neurologic deficit was complete, decompressive surgery should be performed within 36 hours (11). conservative treatment has been suggested just in cases that neurologic deficit improves in the early phase of disease or coagulopathy disorder subjects (12). functional recovery mostly depends on duration of symptoms at presentation and its improving after 72 hours is rare, although some cases improved without surgery has been reported. two cases were showed by hentsched et al. in 2001, one with complete quadriplegia and another one with complete paraplegia that both of them were cured without surgery and had good neurological function during three months following. another study was performed by kim t and colleagues that 15 patients were evaluated in to two groups. ten patients underwent decompressive surgery and the rest conservative treatment. these two groups did not show any difference in initial neurological status after treatment (10). it seems that the hematoma length is a clue in aspect of spontaneous recovery happens in some sseh cases (11, 13). in confronting with a patient complains from the pain, one of the important and priority duties of the physician is relieving the pain. but it is not enough alone and a logical diagnosis is required for justify the pain. of course noticing to the limited time and facilities in the ed, sometimes there is no possibility to the definitive diagnosis. however, at least it should be rule out the critical causes and only in such condition, it is reasonable to discharge the patient to outpatient followup. in the case of unknown psychiatric and neurologic manifestations, measuring serum level of thyroid hormones and csf titer of anti-thyroid antibodies could be helpful in limitation of differential diagnosis and timely initiation of proper treatment. acknowledgments: none conflict of interest: authors declared no conflict of interest. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. blount j, doughty k, tubbs rs, et al. in utero spontaneous cervical thoracic epidural hematoma imitating spinal cord birth injury. pediatr neurosurg. 2004;40(1):23-7. 2. deyo ra, mirza sk, martin bi. back pain prevalence and visit rates: estimates from us national surveys, 2002. spine. 2006;31(23):2724-7. 3. ghafarzad a, tagizadieh a, moharamzadeh p, majidi g. thoracic pneumorrhachis in patient with lumbar fractures; a case report. emergency. 2014;2(2):96-7. 4. hosseini m, karami z, janzadenh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; a experimental study. emergency. 2014;2(4):11-8. 5. binder dk, sonne dc, lawton mt. spinal epidural hematoma. neurosurg q. 2004;14(1):51-9. 6. miyagi y, miyazono m, kamikaseda k. spinal epidural vascular malformation presenting in association with a spontaneously resolved acute epidural hematoma: case report. j neurosurg. 1998;88(5):909-11. 7. adam m, leblebici b, akman mn. spontaneous spinal epidural hematoma related to warfarin therapy: a case report. j back musculoskelet rehabil. 2007;20(1):11-4. 8. marx ja, hockberger rs, walls rm, adams ga. rosen's emergency medicine: concepts and clinical practice. 6th ed. philadelphia: mosby incorporated; 2010. p. 605-675. 9. matsumura a, namikawa t, hashimoto r, et al. clinical management for spontaneous spinal epidural hematoma: diagnosis and treatment. spine j. 2008;8(3):534-7. 10. riaz s, jiang h, fox r, lavoie m, mahood jk. spontaneous spinal epidural hematoma causing brown-sequard syndrome: case report and review of the literature. j emerg med. 2007;33(3):241-4. 11. liu z, jiao q, xu j, wang x, li s, you c. spontaneous spinal epidural hematoma: analysis of 23 cases. surg neurol. 2008;69(3):253-60. 12. tailor j, dunn if, smith e. conservative treatment of spontaneous spinal epidural hematoma associated with oral anticoagulant therapy in a child. childs nerv syst. 2006;22(12):1643-5. 13. groen r. non-operative treatment of spontaneous spinal epidural hematomas: a review of the literature and a comparison with operative cases. acta neurochir (wien). 2004;146(2):103-10. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 144 emergency 2014; 2 (3): 144-146 case report hashimoto encephalopathy in case of progressive cognitive impairment; a case report abbas tafakhori1, bahaadin siroos1*, mojdeh ghabaii1, mohammad hossein harirchain1, masih tajdini1, sushil kumar garg2 1. department of neurology, iranian center of neurological research, tehran university of medical sciences, tehran, iran 2. department of surgery, university of minnesota, minneapolis, usa abstract hashimoto's encephalopathy (he) is a rare condition characterized by atypical psychiatric and heterogeneous neurological manifestations such as acute cerebral ischemia, seizure, tremors, myoclonus, psychosis, depression, cognitive disorders, and fluctuating loss of consciousness. here, a case of 28 year-old man was reported who referred to the emergency department (ed) with different acute neurologic disorders and final diagnose of he. key words: encephalopathy; unconsciousness; cognition disorders; immunoglobulins, thyroid-stimulating; neurologic manifestations cite this article as: tafakhori a, siroos b, ghabaii m, harirchain mh, tajdini m, kumar garg s. hashimoto encephalopathy in case of progressive cognitive impairment; a case report. emergency. 2014;2(3):144-6. introduction: 1 ashimoto's encephalopathy (he) is a rare condition characterized by atypical psychiatric and heterogeneous neurological manifestations such as acute cerebral ischemia, seizure, tremors, myoclonus, psychosis, depression, cognitive disorders, and fluctuating loss of consciousness (1-3). despite a wealth of studies identifying the etiology of he, its exact pathogenesis is not still completely understood (4, 5). due to non-specific findings it is often considered to be a diagnosis of exclusion. currently, he is considered to be a treatable dementia but there is no consensus on the duration or drug of choice for treatment. here, a case of 28 year-old man was reported who referred to the emergency department (ed) with different acute neurologic disorders and final diagnose of he. case report: a previously healthy 28 year-old man was referred to the ed with a history of ophthalmoplegia and ataxia followed by progressive cognitive impairment. two months prior to this episode, mild neck pain and sore throat were the only findings in his past medical history. he had no history of alcohol consumption, substance abuse, medication use, congenital disease, syncope, ischemic or hemorrhagic cerebrovascular attract, seizure, trauma, or any other known medical problems. the patients’ on-arrival vital signs were as follow: systolic blood pressure (sbp): 120 *corresponding author: bahaaddin siroos, m.d; department of neurology, iranian center of neurological research, tehran university of medical sciences, tehran iran. phone/fax: +982161192424/+982166581558. email: bsiroos@razi.tums.ac.ir received: july 2014; accepted: july 2014 mmhg, pulse rate (pr): 90/minute, respiratory rate (rr): 14/minute, oral temperature: 37.5◦c, oxygen saturation 96% with nasal cannula and 100% oxygen, and glasgow coma scale (gcs) 15/15. physical examination revealed jerky movements in limbs, normal size and reactive pupils, fluctuating disorientation, severe cerebral ataxia, bilateral sixth nerve and upward gaze palsy, and increased deep tendon reflexes. a mini mental state examination resulted in 10 of 30 points. the patients’ head and neck examination, lung and heart sounds, four limbs pulses, and capillary refile were normal. after assessment of airway, breathing, and circulation (abc) patients were checked in terms of coma cocktail. blood sugar was measured 100 mg/dl with glucometer. electrocardiography (ecg) revealed normal sinus rhythm with normal axis. brain computed tomography had not any abnormal findings, but bilateral hyper-signal white matter lesions were detected on fluid attenuation inversion recovery (flair) and t2 weighted magnetic resonance imaging (mri) (figure 1). cerebrospinal fluid (csf) analysis results were as follows: protein: 170 mg/dl, glucose: 67 mg/dl, cell count: 80/mm3 with lymphocyte dominancy. all of laboratory parameters as cell blood count, coagulation profile, kidney and liver function tests, venous blood gas parameters, and electrolyte were in normal range. neurology consult was taken and patient admitted in neurology ward for further evaluations. electroencephalography showed abnormal nonspecific sharp and spike waves in a slow background. neural antibodies such as anti–n-methyl-d-aspartate receptor (nmdar) were negative. thyroid statues demonstrated subclinical hypothyroidism. anti-thyroglobulin and anti-peroxidase antibodh mailto:bsiroos@razi.tums.ac.ir this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 145 tafakhori et al ies were 220 iu/ml and 740 iu/ml, respectively, which were significantly higher than normal ranges. all other assessments were normal. taking the above data into consideration and excluding other differential diagnosis, he was presumed. the patient underwent ten days of methyl prednisolone pulse regime (one gram per day) with tapering prednisolone (120 mg orally per day) for two weeks. all signs and symptoms especially cognition and ophthalmoplegia dramatically improved and white matter lesions disappeared after two weeks of treatment (figure 2). discussion: heterogeneous clinical manifestations and absence of non-specific tests have made the he diagnosis as a challenging problem for physicians. susan lee et al. in a review concluded that psychiatrists should be aware of this often unrecognized entity to ensure accurate diagnosis and timely treatment (6). he has different mri manifestations from normal appearance to demyelination, ischemic lesions, edema, and atrophy (7). usually, he is diagnosed by high levels of anti-tpo antibodies, normal t4, and thyroid stimulating hormone (tsh) titers in the presence of above mentioned heterogeneous clinical manifestations (8). recent studies have suggested cerebrospinal fluid titer of anti-thyroid antibodies as a pathognomonic test for he (1, 9). according to the published case series, steroid is the only accepted treatment for this disease and among 81 adults and children, about 50% of patients recovered completely and the other cases relapsed or improved with residual deficits (10, 11). previous studies have recommended three to five days corticosteroids (12). the present study is the first one that give the patient 10 days of methyl prednisolone. the patient responded completely to the corticosteroid. it seems that a favorable prognosis may depend upon rapid recognition of he and aggressive steroid treatment. however, further studies are needed to evaluate the advantage of this type of treatment for disease. conclusion: in the case of unknown psychiatric and neurologic manifestations, measuring serum level of thyroid hormones and csf titer of anti-thyroid antibodies could be helpful in limitation of differential diagnosis and timely initiation of proper treatment. acknowledgments: none conflict of interest: authors declared no conflict of interest. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. de holanda ncp, de lima dd, cavalcanti tb, lucena cs, bandeira f. hashimoto's encephalopathy: systematic review of the literature and an additional case. j neuropsychiatry clin neurosci. 2011;23(4):384-90. 2. ferracci f, bertiato g, moretto g. hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations. j neurol sci. 2004;217(2):165-8. 3. chong jy, rowland lp, utiger rd. hashimoto encephalopathy: syndrome or myth? arch neurol. 2003;60(2):164-71. 4. oide t, tokuda t, yazaki m, et al. anti-neuronal autoantibody in hashimoto's encephalopathy: neuropathological, immunohistochemical, and biochemical analysis of two patients. j neurol sci. 2004;217(1):7-12. 5. muramatsu t, ikawa m, yoneda m, et al. pathophysiological decrease in the regional cerebral blood flow in hashimoto's encephalopathy: a multiple-case spect study. eur neurol. 2014;72(1-2):13-9. 6. lee sw, donlon s, caplan jp. steroid responsive encephalopathy associated with autoimmune thyroiditis (sreat) or hashimoto's encephalopathy: a case and review. psychosomatics. 2011;52(2):99-108. 7. chen n, qin w, wei c, wang x, li k. time course of hashimoto's encephalopathy revealed by mri: report of two cases. j neurol sci. 2011;300(1):169-72. 8. mamoudjy n, korff c, maurey h, et al. hashimoto's figure 1: fluid attenuation inversion recovery shows symmetric white matter lesion before treatment  figure 2: fluid attenuation inversion recovery shows improvement in white matter lesion after treatment  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 146 emergency 2014; 2 (3): 144-146 encephalopathy: identification and long-term outcome in children. eur j paediatr neurol. 2013;17(3):280-7. 9. yoneda m, fujii a, ito a, yokoyama h, nakagawa h, kuriyama m. high prevalence of serum autoantibodies against the amino terminal of alpha-enolase in hashimoto's encephalopathy. j neuroimmunol. 2007;185(1-2):195-200. 10. imperiale d, labate c, testi r, romito a, taraglio s. clinical and neuropathological findings in hashimoto’s encephalopathy: a case report. neurol sci. 2014;35(2):327-9. 11. tang y, xing y, lin mt, zhang j, jia j. hashimoto’s encephalopathy cases: chinese experience. bmc neurol. 2012;12(1):60. 12. mijajlovic m, mirkovic m, dackovic j, zidverc-trajkovic j, sternic n. clinical manifestations, diagnostic criteria and therapy of hashimoto's encephalopathy: report of two cases. j neurol sci. 2010;288(1):194-6. archives of academic emergency medicine. 2022; 10(1): e40 ca s e re p o rt prolonged resuscitation with multiple defibrillations; a case report shaghayegh rahmani1, elham mokhtari amirmajdi2, rana kolahi ahari3∗, roohie farzaneh4 1. innovated medical research center, faculty of medicine, mashhad branch, islamic azad university, mashhad, iran. 2. department of internal medicine, mashhad branch, islamic azad university, mashhad, iran. 3. faculty of medicine, mashhad branch, islamic azad university, mashhad, iran. 4. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, iran. received: march 2022; accepted: april 2022; published online: 26 may 2022 abstract: although american heart association guidelines (aha) are practical and standardized in many aspects of cardiopulmonary resuscitation (cpr) performance, recommendations on when to terminate resuscitation are not fully understood and clear. there is not enough evidence about how long we can continue cpr in shockable rhythms and how many shocks can be delivered to patients, and if there is an end point for it or not. this issue is more challenging when we read papers published on survival rates and good functional and neurological outcomes after prolonged cprs. here, we demonstrate a case of cardiac arrest receiving cpr in the emergency room, for whom it was hard and challenging to make a decision on when to terminate the resuscitation attempts. keywords: cardiopulmonary resuscitation; electric countershock; heart arrest cite this article as: rahmani s, mokhtari amirmajdi e, kolahi ahari r, farzaneh r. prolonged resuscitation with multiple defibrillations; a case report. arch acad emerg med. 2022; 10(1): e40. https://doi.org/10.22037/aaem.v10i1.1583. 1. introduction cardiopulmonary resuscitation (cpr) consists of a group of life-saving interventions, which aid in oxygenation and circulation when cardiac arrest happens (1). cardiac arrest onset is defined as absence of palpable central pulse, apnea, or unresponsiveness. when cpr performance is stopped for a patient without the return of spontaneous circulation (rosc), the patient is considered terminated (2, 3). performing a high-quality cpr is a challenging issue. although there are exact guidelines about its performance, some cases may be more complicated. there is no agreement on which patients need prolonged conventional cpr and which patients are not good candidates for it. in most cases, it varies across hospital protocols (3) and is based on subjective team decision (4). despite advancements in resuscitation, recent published data showed exceedingly poor outcomes for outand in-hospital cprs (5). the rate of survival with favorable neurologic out∗corresponding author: rana kolahi ahari; faculty of medicine, mashhad branch, islamic azad university, mashhad, iran. phone/fax number: +989362943344, email: kolahi.rana@gmail.com, orcid: http://orcid.org/0000-0002-3681-7528. come is even lower (4). although american heart association (aha) guidelines are practical and standardized in many aspects of cpr performance, recommendations on when to terminate resuscitation are not fully understood and clear. there is not enough evidence about how long we can continue cpr in shockable rhythms and how many shocks can be delivered to patients, and if there is an end point for it or not. this issue appears to be even more challenging when we read published papers about survival rates and good functional and neurological outcomes after prolonged cprs. here, we demonstrate a case of cardiac arrest receiving cpr at the emergency department, for whom it was hard and challenging to make a decision on when to terminate the resuscitation attempts. 2. case presentation a 30-year-old male presented to the emergency department (ed) with cardiac arrest. he had had a seizure-like attack and cardiac arrest at home, no one performed basic life support for him. his family called emergency medical services (ems), and within 5 minutes they reached the patient and advanced cardiac life support treatment, including endotracheal intubation and chest compressions based on aha guideline 2020 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. rahmani et al. 2 version, was initiated for him. the initial rhythm was not shockable. during cpr, automated external defibrillator (aed) delivered two shocks. he also received 1 mg epinephrine. the patient was transferred to our emergency department, 22 bahman hospital, mashhad, iran, about 15 minutes after cardiac arrest. his first rhythm was asystole in hospital. cpr was continued. after two minutes, rhythm was checked. it was ventricular fibrillation, he was defibrillated seventeen times, and received 1 mg epinephrine each three minutes, 300 mg intravenous (iv ) amiodarone, followed by 150 mg iv amiodarone. the emergency department cardiac arrest team, which was being led by an emergency medicine specialist, continued with high quality cpr (our center does not have a cardiology unit). other recommended medications that were used for this patient included: 1 mg/kg of sodium bicarbonate and lidocaine, and 2 g of magnesium empirically. the laboratory test results such as hemoglobin, coagulation state, kidney function test, and blood electrolytes were normal. about 10 minutes after the last antiarrhythmic drug use, his rhythm was converted to sinus with a palpable carotid pulse. the quality of cpr was monitored using the pressure of end-tidal co2 (petco2). the return of spontaneous circulation (rosc) was confirmed by increase in end tidal co2, from around 20 mmhg to 50 mmhg. ed cpr lasted about 50 minutes, and the patient had received out-of-hospital cpr for 10 minutes. patient’s rhythm was shockable during a long portion of cpr period. in the post-resuscitation period, liver function test (lft) results was impaired, with a positive methadone test. he was transferred to intensive care unit (icu) but he was expired shortly thereafter. other tests, such as ionogram, were normal. troponin was positive in first blood sample, unfortunately our hospital lab did not report it as a quantitative value. 3. discussion we introduced a prolonged cpr case with shockable rhythm without underlying heart disease. the mentioned patient was young, with no cardiopulmonary complaints before arrest, and his post-rosc electrocardiograph was normal sinus rhythm with no st segment changes. his past medical history, physical examination, and preclinical evaluation showed no evidence regarding cardiologic problems whatsoever. this case was confusing because of numerous defibrillations and use of variable antiarrhythmic agents during cpr. he had systole rhythm for only one cycle, it is assumed that this rhythm might have been fine ventricular fibrillation (vf) that changed to ventricular tachycardia (vt) after epinephrine administration. for our case, methadone toxicity might be an important underlying cause of arrhythmia, because such drugs can lead to prolonged qt interval. but in the electrocardiography (ecg) performed after rosc, qt interval was normal. bedsides, echocardiography, performed by an emergency medicine specialist, was also reported to be almost normal. so structural and electrical abnormality can be ruled out in our patient. so, the exact cause of this resistant arrhythmia is not fully determined. generally, studies regarding the effect of duration of cardiopulmonary resuscitation on clinical outcome are few. a case study of prolonged resuscitation due to torsade de pointes with 99 defibrillations shows survival with good neurological outcome (5). conformingly, bingyu ling et al. described a case who had developed cardiac arrest due to propafenone intoxication and was successfully resuscitated after prolonged cpr without subsequent neurological complication (6). it seems that, intoxication might lead to cardiac arrest with shockable rhythm without basic cardiologic problems. although our patient was a drug user (methadone), his family did not confirm any overdose or suicidal effort. urine analyses showed methadone, but we were not able to measure its concentration level. prolonged cpr is a decision for physician and its outcome depends on various factors, like cpr quality. we tried to improve in-hospital cpr quality with regular staff training programs, selecting and announcing resuscitation code members daily, with defined positions for each of the six persons and assigning an emergency specialist or icu physician as a cpr team director. the baseline status of the patient is another factor that would influence the duration of resuscitation, including patient’s age and coexisting comorbidities. our patient was young without underlying diseases. due to the corona virus pandemic and increasing risk of pulmonary thromboembolism (pte), bedside echocardiography was performed by an emergency medicine specialist post-rosc, but it revealed no evidence of pte. we were unable to find a reversible cause for cardiac arrest in our case. sudden cardiac death in all age groups is estimated to be responsible for 350000 deaths in the usa each year, and the survival rate is about 8% (7). the aha’s advanced cardiac life support (acls) guideline recommends immediate initiation of high-quality cpr, early defibrillation, and the administration of epinephrine and antiarrhythmic agents for the management of vf and pulseless vt (2). so, this should be a reminder for physicians to continue high quality cpr and shocking with less interruption in a specific group of cardiac arrest patients. but the maximum duration is still unclear. another important aspect is the critical role of percutaneous coronary intervention (pci) in post-cardiac arrest. coronary angiography is recommended emergently for patients with suspected cardiac etiology of arrest and st elevation on ecg, it is logical to transfer patients like ours to cardiology or anthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e40 giography units, since there was no evidence of heart disease in our patient but he had inexplicable rhythm during cpr with normal ionogram. 4. conclusion the maximum duration of resuscitation attempts for incrementing survival has not been established and it may vary from one patient to another. considering the major factors that affect the outcomes of resuscitation, guidelines should better set clear and standard recommendations on optimal and most appropriate duration of cpr for patients with cardiac arrests and shockable rhythms. further studies should be performed with regards to prolonged cpr, analyzing the different aspects relating to prolonged cpr and its outcomes. 5. declarations 5.1. acknowledgments we would like to express our special thanks to our patient’s relatives and our cpr team. 5.2. authors’ contributions all authors discussed the results and contributed to the final manuscript. 5.3. funding and supports we do not have a funding resource. 5.4. conflict of interest the authors have no conflicts of interest. 5.5. ethical considerations the authors adhered to confidentiality of patient’s profile and ethical consideration regarding the biomedical researches. references 1. barker j, koeckerling d, west r. a need for prone position cpr guidance for intubated and non-intubated patients during the covid-19 pandemic. resuscitation. 2020;151:135-6. 2. nolan jp, monsieurs kg, bossaert l, bottiger bw, greif r, lott c, et al. european resuscitation council covid-19 guidelines executive summary. resuscitation. 2020;153:45-55. 3. costa i, bittar cs, rizk si, araujo filho ae, santos kaq, machado tiv, et al. the heart and covid-19: what cardiologists need to know. arq bras cardiol. 2020;114(5):805-16. 4. kramer db, lo b, dickert nw. cpr in the covid-19 era an ethical framework. n engl j med. 2020;383(2):e6. 5. taha hs, shaker mm, abdelghany mm. cardiopulmonary resuscitation during the covid-19 pandemic: a scientific statement on cpr management protocol of kasr al-ainy university hospital is presented. egypt heart j. 2020;72(1):73. 6. hwang cw, gamble g, marchick m, becker tk. a case of refractory ventricular fibrillation successfully treated with low-dose esmolol. bmj case rep. 2019;12(3): e228208. 7. herlitz j ej, svensson l, young m, angquist ka, holmberg s. decrease in the occurrence of ventricular fibrillation as the initially observed arrhythmia after out-of-hospital cardiac arrest during 11 years in sweden. resuscitation. 2004;3(60):283-90. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem archives of academic emergency medicine. 2022; 10(1): e42 or i g i n a l re s e a rc h an 18-month epidemiologic survey of 3364 deceased covid-19 cases; a retrospective cross-sectional study ayoub tavakolian1, seyed hassan ashrafi shahri2, mohammad ali jafari3, elham pishbin2, hamid zamani moghaddam2, mahdi foroughian2, hamidreza reihani2∗ 1. department of emergency medicine, faculty of medicine, sabzevar university of medical sciences, sabzevar, iran. 2. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. department of emergency medicine, faculty of medicine, shahid sadoughi university of medical sciences, yazd, iran. received: february 2022; accepted: march 2022; published online: 31 may 2022 abstract: introduction: the covid-19 pandemic has been considered an international problem. this study aimed to survey the demographic and clinical characteristics of the deceased covid-19 patients. methods: the present cross-sectional study was performed on all deceased covid-19 patients who died in imam reza hospital, mashhad, iran, from march 20, 2020, to september 23, 2021. their data, including age, gender, complaints, and clinical symptoms at the time of admission, as well as information at the time of death (hour, shift, holiday/nonholiday) were analyzed and reported. results: 3364 deaths due to covid-19 have been registered during the study period (60.46% male). the patients’ mean age was 66.99±16.97 (range: 1-101) years (92.7% of them were iranian). the mortality at night shifts was less than day shifts (1643 vs. 1721). the average amount of deaths/day on holidays and workdays was (5.63 vs. 6.24). the number of deaths varied during the various hours of the day and night. diabetes and cardiovascular diseases were the most common confounding factors, which were observed in 22.44% and 15.36% of the cases, respectively. conclusion: based on the findings of this series, covid19 mortality was frequently observed in male patients, those with the mean age of 66.99 years, morning shifts, and workdays. keywords: covid-19; hospital mortality; diabetes mellitus; cardiovascular diseases cite this article as: tavakolian a, ashrafi shahri sh, jafari ma, pishbin e, zamani moghaddam h, foroughian m, reihani h. an 18-month epidemiologic survey of 3364 deceased covid-19 cases; a retrospective cross-sectional study. arch acad emerg med. 2022; 10(1): e42. https://doi.org/10.22037/aaem.v10i1.1568. 1. introduction sars-cov-2, a member of the coronaviridae family, caused a disease named covid-19 in the late 2019, which became a widespread infection in world (1, 2). sars-cov-2 can cause various ranges of the clinical symptoms from mild manifestations to severe forms of disease requiring intensive care unit (icu) admission (3-7). acute respiratory distress syndrome (ards) is the main cause of death from covid-19 (8, 9). pooled analyses of mortality rates have demonstrated extensively higher rates of mortality among icu admitted patients (40.5%) compared to ward admitted ones (11.5%) (10). various studies are con∗corresponding author: hamidreza reihani; emam reza hospital, ibn-sina street, mashhad, iran. email: reihanihr@mums.ac.ir, tel: +98 9153173869, orcid: http://orcid.org/0000-0003-0617-9374. ducted to predict mortality rate and distinguish indices related to severity of covid-19 and its mortality, as well as to investigate biochemical, laboratory, clinical, and imaging characteristic of patients (11, 12). additionally, some astounding findings have pointed to the significant effects of the spatiotemporal factors as well (13, 14). zhang et al. reported that shift work at night was linked to a higher risk of mortality (14). but morales et al. showed that being admitted to icu at night does not correlate to higher mortality rate of covid-19 patients (15). understanding the impact of different times of the day on the quality of care, and finding other potentially influential factors would provide the opportunity for applying proper policies. so, this study aimed to evaluate the demographic and clinical findings of deceased covid-19 cases, stratified by death time in a referral hospital in northeast of iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. tavakolian et al. 2 2. methods 2.1. study design and setting in the present retrospective cross-sectional study, characteristics of 3364 deceased covid-19 patients in imam reza hospital, mashhad, as one of the referral centers for covid19 patients in north-east of iran, from march 20, 2020, until september 23, 2021 (about 18 months), were reviewed. after obtaining approval from mashhad university of medical sciences ethics committee (code: ir.mums.rec.1399.242), information about all deceased patients with confirmed covid-19 diagnosis based on international guidelines was collected from the archives of the hospital using census method. researchers adhered to confidentiality of patients’ information and ethical considerations stated in declaration of helsinki. 2.2. participants the present study includes all cases of hospital mortalities due to covid-19 during the study period. all cases of mortalities attributed to covid-19 by an infectious disease specialist was considered in this study, even cases with underlying health conditions. records of patients who were transferred from other centers were also included. patients who did not meet the icd-10 criteria for covid-19 diagnosis were excluded. patients who had died after being transmitted to other hospitals were not included. ethnicity was not considered when gathering data and refugees were also included. 2.3. data gathering the collected data include age, gender, postal address, complaints and clinical symptoms, o2 saturation at the time of admission, as well as information on the time of death (hour, shift, holiday/workdays). a checklist of the mentioned factors was provided by researchers and filled out, retrospectively, by reviewing hospital records. only records containing a positive pcr result for covid-19 were recruited. 2.4. statistical analysis the collected data were analyzed using spss software version 26. descriptive statistics for qualitative variables were reported in the form of frequency and frequency distribution and those of quantitative variables were reported as mean and standard deviation. the normality of quantitative variables was confirmed using the kolmogorov-smirnov test. 3. results 3364 deaths due to covid-19 were recorded during the study period (2034 (60.46%) male and 1330 (39.54%) female). the mean age was 66.99 ± 16.97 (range: 1 -101; median: 68) years with normal distribution (50% > 67 and 25% < 56 years). table 1 shows the baseline characteristics of studied patients. the most common complaint was shortness of breath (74.23%) followed by cough (34.0%). 88.59% of patients had a decrease in o2 saturation at the time of admission to the hospital. 1321/2015 (65.56%) patients with complete clinical information had at least one underlying disease. (15.36% heart disease and 22.44% diabetes mellitus). 3.1. mortality peaks figure 1 shows a comparison of the total number of covid19-associated deaths during each peak. during the study period, five mortality peaks was observed. during the first one (from march 20, 2020, up to june 3, 2020), which occurred in the first month of the covid-19 pandemic, a total of 309 people died and the average daily death rate was 4.07±2.91 deaths/day. in the second peak ( june 11 up to august 26, 2020), during which 911 covid-19 deaths was recorded, the average daily number of deaths was 11.99±8.06 deaths/day. the third and fourth waves of death due to coronavirus occurred at the end of 2020 and the first half of 2021. the fifth wave occurred from july 7, 2021, until september 20, 2021, in which 1042 covid-19 deaths were recorded with a daily average number of 13.71± 8.28. at the same time, the highest mortality rate was recorded, with 34 deaths in one day. this peak was larger than the other peaks in terms of intensity and extent. the second and fifth peaks were more severe and there were a higher number of patients with worse conditions compared to the other waves. 3.2. age distribution figure 2 shows the age distribution of deceased cases stratifying study periods to 3-month parts. least deaths were reported in individuals less than 20 years old with 59 (1.75%) cases, followed by twentyto forty-year-old subjects with 281 (8.35%) cases. the highest number of death reports, 1516 (45.07%) cases, belonged to those 60 to 80 years old followed by those 40 to 60 years old and over 80 years old with 732 (21.76%) and 776 (23.07%) cases, respectively (p < 0.001). 3.3. time distribution the lowest death rate is recorded in the early hours of the morning with 103(3.06%) deaths and the highest death rate is recorded in 11-12 am with 170 (5.05%) deaths (figure 3). in the morning shift, 884 patients died with an average of 1.61 ± 2.41 deaths/day, and in the evening shift, 837 people died with an average of 1.52±2.25 deaths/day. by a division of the night shift into two shifts from 19 in the evening till 1 in the morning and the other shift from 1 am till 7 am an average death rate of 1.58 ±2.38/day and 1.41± 2.08/day were recorded, respectively (figure 4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e42 3.4. day distribution the present study period covers a total of 115 holidays and 435 workdays. the average covid-19 mortality rate was 5.58 deaths/day (642 cases) on holidays and 6.27 deaths/day (2722 deaths) on workdays. 4. discussion based on the findings of this series, the covid-19 mortalities were frequently observed in males, patients with the mean age of 66.99 years, morning shifts, and workdays. preliminary reports of covid-19 epidemiology in china show that the mortality rate of males (2.8%) is higher than females (1.7%) (16). mir jalili et al. reviewed the risk factors of covid-19 patients’ mortality in a case-cohort study and reported that 56.1% of the deceased patients are male, and their mean age is 71 years (17). another study on covid-19 mortality in ten major european countries reported that men had a higher death rate than women. covid-19-related death risk ranged from rr = 1.11 in portugal to rr = 1.54 in france (18). hannah et al., in a large meta-analysis of more than three million covid-19 patients in 44 countries, indicate that gender does not play a role in covid-19 infection, but in the case of covid-19, male patients have three times more chance of icu admission and death (or = 1.39,95% cl = 1.31,1.47) (19). in the present study, similar to most studies, males accounted for more deaths (60.46%) than females. ghasemian et al. reviewed the medical files of deceased covid-19 cases and found that their mean age was 63.36 years with a standard deviation of 15.26 years. 43% of patients were under 60 years old and 42.3% of patients were in the age group of 60-80 years (20). in the present study, the mean age of the patients was 67 and their median age was 68 years. 71.7% of patients were over 60 years old. in the age range of 60-69 years, total death count equaled 25.6%. during our study, the top five mortality peaks occurred. the fifth peak occurred from july 7, 2021 until september 20, 2021, in which 1042 covid-19 patients died (a daily average mortality rate of 17.31 patients/day). in the twentythird epidemiological report of covid-19 disease in fars province, published by shiraz university of medical sciences, five peaks in mortality rate due to coronavirus were reported. the second and fifth peaks were more extensive, which conform with our study (21). the results of a study conducted in canada indicated that in the case of some medical emergencies, the mortality rate of patients admitted to the emergency room on holidays is significantly higher (22). also, based on the results of a study conducted in japan on 1134 patients, it was found that if the patient is admitted on workdays of the week, the prognosis of the disease will be better (23). in the present study, the mortality rate reported in the morning shifts was significantly higher compared to other shifts. in our study, covid-19 death counts varied at various times during the day and night. according to our study, 2722 covid-19 deaths were reported on workdays (mean 6.27 ± 6.5), while 642 deaths were confirmed on holidays (mean 5.58 ± 6.05). this result was in contrast to other studies and needs further investigation. according to our study, the most common patient complaint was shortness of breath. 5. limitations our study was a retrospective review of hospital records, in some of which data were missing, and we could not examine more detailed hypotheses. also, the records were registered by different persons, each of which might have their own definition for the different concepts used in the study as well as symptoms. 6. conclusion based on the findings of this series, the covid-19 mortalities were frequently observed in males, patients with mean age of 66.99 years, morning shifts, and workdays. 7. declarations 7.1. acknowledgments the present review is a portion of dr. seyed hassan ashrafi shahri’s thesis, with an approved code of ethics ir.mums.rec.1399.242. the financial support, guidance, and advice of the clinical research development unit of imam reza hospital are appreciated. 7.2. authors’ contributions this study was designed and registered by shas, mj, and mf. ep, hzm, mf, and hr participated in data collection. data preprocess was performed by hzm and shas. data analysis was performed by mf and shas. all authors contributed to literature review and manuscript writing as well as the revisions. 7.3. funding and supports this study was supported by mashhad university of medical sciences. 7.4. conflict of interest the researchers claim no conflicts of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. tavakolian et al. 4 references 1. docea ao, tsatsakis a, albulescu d, cristea o, zlatian o, vinceti m, et al. a new threat from an old enemy: re-emergence of coronavirus. international journal of molecular medicine. 2020;45(6):1631-43. 2. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 3. kotfis k, roberson sw, wilson je, pun bt, ely ew, jeżowska i, et al. covid-19: what do we need to know about icu delirium during the sars-cov-2 pandemic? anaesthesiology intensive therapy. 2020;52(2):132. 4. ghanaatpishe a, sohrabpour m, sadegh m, jahromi s, habibzadeh sr, shahi b, et al. worldwide one-year dynamics of covid19 manifestations: a systematic review and metaanalysis. updates in emergency medicine. 2021. 5. rahmanian f, hatami n, haghbeen m, raoufi r, abbasi ar, shakeri h, et al. gender differences in covid-19 deceased cases in jahrom city, south of iran. bulletin of emergency & trauma. 2021;9(2):80. 6. kalani n, hatami n, ali s, mehramiz nj, rahmanian f, doost er, et al. self-referred walk-in (srw ) versus emergency medical services brought covid-19 patients. bulletin of emergency & trauma. 2022;10(1):21. 7. sahraeai r, sarikhani y, kalani n, hatami n, abiri aa, eftekharian f. prevalence of gastrointestinal symptoms in patients with covid-19 in jahrom county, fras province, southwest of iran. journal of medicinal and chemical sciences, 2022. 5(4): p. 483-490. 8. gibson pg, qin l, puah sh. covid-19 acute respiratory distress syndrome (ards): clinical features and differences from typical pre-covid-19 ards. medical journal of australia. 2020;213(2):54-6. e1. 9. xu z, shi l, wang y, zhang j, huang l, zhang c, et al. pathological findings of covid-19 associated with acute respiratory distress syndrome. the lancet respiratory medicine. 2020;8(4):420-2. 10. macedo a, gonçalves n, febra c. covid-19 fatality rates in hospitalized patients: systematic review and metaanalysis. annals of epidemiology. 2021;57:14-21. 11. bertsimas d, lukin g, mingardi l, nohadani o, orfanoudaki a, stellato b, et al. covid-19 mortality risk assessment: an international multi-center study. plos one. 2020;15(12):e0243262. 12. javdani f, parsa s, shakeri h, hatami n, kalani n, haghbeen m, et al. phosphate levels and pulmonary damage in covid-19 patients based on co-rads scheme: is there any link between parathyroid gland and covid-19? medrxiv. 2020. 13. bermudi pmm, lorenz c, de aguiar bs, failla ma, barrozo lv, chiaravalloti-neto f. spatiotemporal dynamic of covid-19 mortality in the city of são paulo, brazil: shifting the high risk from the best to the worst socioeconomic conditions. arxiv preprint arxiv:200802322. 2020. 14. zhang s, xu y, wu k, wang t, su x, han q, et al. improved night shift schedule related to the mortality of critically ill patients with corona virus disease 2019. sleep medicine. 2020;75:354-60. 15. morales ij, peters sg, afessa b. hospital mortality rate and length of stay in patients admitted at night to the intensive care unit. critical care medicine. 2003;31(3):85863. 16. dudley jp, lee nt. disparities in age-specific morbidity and mortality from sars-cov-2 in china and the republic of korea. clinical infectious diseases. 2020;71(15):863-5. 17. mirjalili m, dehghani m, raadabadi m, dehghani a. death risk among covid-19 patients in yazd, iran: a hospital-based case-cohort study. journal of military medicine. 2021;23(3):274-82. 18. ahrenfeldt lj, otavova m, christensen k, lindahljacobsen r. sex and age differences in covid-19 mortality in europe. wiener klinische wochenschrift. 2021;133(7):393-8. 19. peckham h, de gruijter nm, raine c, radziszewska a, ciurtin c, wedderburn lr, et al. male sex identified by global covid-19 meta-analysis as a risk factor for death and itu admission. nature communications. 2020;11(1):1-10. 20. ghasemian r, alizadeh-navaei r, boskabadi j, rezaei kalantari k. clinical features and paraclinical findings of patients died of covid-19 in a referral hospital in sari, iran, february 2020-may 2020. journal of mazandaran university of medical sciences. 2021;31(198):119-32. 21. covid-19 epidemiological committee. shiraz medical school science, 23rd covid-19 epidemiological data report in fars. covid-19-19 in fars, shiraz university pub. 2021. 22. bell cm, redelmeier da. mortality among patients admitted to hospitals on weekends as compared with weekdays. new england journal of medicine. 2001;345(9):6638. 23. hasegawa y, yoneda y, okuda s, hamada r, toyota a, gotoh j, et al. the effect of weekends and holidays on stroke outcome in acute stroke units. cerebrovascular diseases. 2005;20(5):325-31. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e42 figure 1: the frequency of death per day during the five peaks of covid-19 referrals in the studied hospital. figure 2: distribution of covid-19 mortalities based on different age groups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. tavakolian et al. 6 figure 3: distribution of covid-19 mortalities based on the different hours of the day. figure 4: distribution of covid-19 mortalities based on different working shifts. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e42 table 1: baseline characteristics of deceased covid-19 cases variables number * value age (year) mean ± sd 3364 66.99 ± 16.97 gender 3364 male 2034 2034 (60.46) female 1330 1330 (39.54) presenting sign/symptoms fever 2340 530 (22.65) chills 2340 212 (9.06) cough 2340 796 (34.02) sore throat 2340 19 (0.81) dyspnea 2340 1737 (74.23) general weakness 2340 666 (28.46) diarrhea 2340 26 (1.11) nausea/vomiting 1725 61 (3.54) headache 1725 63 (3.65) abdominal pain 1725 37 (2.14) smell disorder 1725 10 (0.58) taste disorder 1725 10 (0.58) saturation o2 < 93% 1954 1731 (88.59) respiratory rate >23/minutes 1827 344 (18.83) data are presented as mean ± standard deviation (sd) or frequency (%). *: number of available data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e22 https://doi.org/10.22037/aaem.v9i1.1172 ca s e re p o rt delayed post-traumatic tension hydropneumocephalus; a case report of conservative treatment talayeh mirkarimi1, ehsan modirian1, peyman namdar1, mohammad salek1∗ 1. emergency department; rajaei hospital, medical faculty, qazvin university of medical science, qazvin, iran. received: january 2021; accepted: january 2021; published online: 27 february 2021 abstract: pneumocephalus refers to the presence of air in the cranial cavity. trauma is the most common cause of acquired pneumocephalus. tension pneumocephalus occurs when intracranial accumulation of air causes high pressure on the brain as compared to extracranial pressure. tension pneumocephalus is usually acute, and causes neurological symptoms, and its delayed form rarely occurs. a 12-year-old girl presented with a headache, lethargy, mild fever, and nausea from two days before admission to emergency department of shahid rajaei hospital, qazvin, iran. the patient had a history of head trauma in a driving accident six weeks before and had undergone brain computed tomography (ct) scan in another centre, which had revealed no sign of pneumocephalus. the patient had been treated for one week and had been discharged in good general condition. considering her reduced consciousness, the patient underwent brain ct scan again in our centre. ct scan revealed tension hydropneumocephalus. the patient was transferred to the intensive care unit (icu) for treatment. considering the trend of her recovery, the patient was a candidate for conservative non-surgical therapy based on the incharge neurosurgery specialist’s decision. the patient reported no complications during the six-month followup. delayed tension pneumocephalus is among neurosurgery emergencies usually treated with early surgical intervention and dura defect restoration, but this patient received non-surgical treatment without any serious problem during the six-month follow-up. keywords: pneumocephalus; craniocerebral trauma; conservative treatment; case reports cite this article as: mirkarimi t, modirian e, namdar p, salek m. delayed post-traumatic tension hydropneumocephalus; a case report of conservative treatment . arch acad emerg med. 2021; 9(1): e22. 1. introduction pneumocephalus refers to a pathologic intracranial accumulation of air, and is categorized as epidural, subdural, subarachnoid, intra-parenchymal, and intra-ventricular types (1). head and facial trauma is the most common cause of pneumocephalus and is responsible for 75% of cases (2). other factors that can cause pneumocephalus include otitis media, skull base tumours, neurosurgical procedures (3), anaesthesia with nitric oxide, positive pressure ventilation, hyperbaric oxygen therapy, barotrauma, spinal anaesthesia, intracranial pressure (icp) monitoring, intraoperative infusion of mannitol (4, 5), and gas-forming infections in the central nervous system (cns). moreover, spontaneous form has been rarely reported (3). intracranial accumulation of gas can be acute (<72 hours) or delayed (>72 hours). pneumo∗corresponding author: mohammad salek; qazvin university of medical sciences, bahonar blvd, qazvin, iran. email: mohammad_salek@yahoo.com, phone number: 00989380912244, orcid: 0000-0002-4612-2746. cephalus is also divided into simple and tension types. tension pneumocephalus refers to the type that causes higher pressure on the brain parenchyma compared to extracranial pressure (6-8). since this type can cause neurological disorders that are potentially life-threatening, such as cerebral herniation, its early diagnosis is highly important (8). here we present the case of a 12-year-old girl who presented with headache, lethargy, mild fever, and nausea from two days before admission to emergency department and history of head trauma 6 weeks before. she was diagnosed with delayed tension hydropneumocephalus and treated by conservative management without any problem during the 6month follow-up. 2. case presentation a 12-year-old girl presented to emergency department of shahid rajaei hospital in ghazvin, iran, with headache, drowsiness, mild fever, nausea, vomiting, and lethargy form two day before admission. the patient had a history of head trauma in a driving accident six weeks before and had this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. mirkarimi et al. 2 been hospitalized in hamedan city, where she had undergone spiral brain computed tomography (ct) scan without contrast due to reduced consciousness. brain ct scan reported right frontal contusion, right frontal bone fracture involving frontal sinus and filling of ethmoid sinuses. the patient had received treatment in that centre for one week and was discharged in good general condition. the patient did not report any history of seizures, otorrhoea, or rhinorrhoea during these six weeks. the presenting vital signs of the patient were as follows: pulse rate: 88/minute, respiratory rate: 18/minute, blood pressure: 105/75 mmhg, axillary temperature: 37.8°c, glasgow coma scale (gcs): 13/15 (eye response = 3, motor response = 6, verbal response = 4). pupils were symmetrical of 3 millimetres and reduced response to light was detected in the right pupil. the four limbs had equal force of 5/5. deep tendon reflexes (dtrs) were 2+ and symmetrical, and bilateral plantar reflex was symmetrical and downward. other clinical examination findings were unremarkable. the patient underwent brain ct scan again in our centre, which revealed hydropneumocephalus in the frontal parenchyma with midline shift and compression effect on the anterior horn of the lateral ventricles in the right frontal lobe (figure 1). thus, the patient underwent treatment with phenytoin and 100% concentration oxygen. moreover, given her mild fever and likelihood of brain abscess, a broadspectrum antibiotic (vancomycin) was administered until magnetic resonance imaging (mri) was done. neurosurgery emergency consultation was requested, and the patient was admitted to the intensive care unit for further treatments. considering the trend of recovery and at the neurosurgeon’s discretion, the patient was a candidate for conservative nonsurgical therapy. mri with contrast on the third day of admission revealed no rim enhancement around the lesion, and confirmed the diagnosis of tension. hydropneumocephalus (figure 2). therefore, antibiotic was discontinued. on the seventh day, the patient was advised to continue taking oral phenytoin, and was discharged in good general condition. the patient reported no complications during the six-month follow-up. 3. discussion two main theories usually explain the mechanism of developing tension pneumocephalus: 1) the ball-valve theory, in which air enters the skull unilaterally, but cannot leave (9, 10). 2) inverted soda valve bottle theory, in which, air is drawn into the skull by the negative pressure created due to reduced cerebrospinal fluid (csf) volume (for whatever reason)(4, 5, 11). headache is the most common symptom of pneumocephalus (12). the clinical presentation of tension pneumocephalus includes headache, generalized seizure, agitation, delirium, abnormal reflexes, changes in consciousness level, and changes in pupil size and response. tension pneumocephalus can mimic the manifestations of an intracranial space occupying lesion, and can lead to signs of brainstem displacement, including changes in respiratory rhythm and cardiac arrest, if it occurs in the posterior cranial fossa (13). brain ct scan is the gold standard for diagnosis of tension pneumocephalus, which can also be diagnosed using plain radiography (3). the typical pathognomonic view of pneumocephalus is referred to as “mount fuji sign”, which is described as bilateral subdural hypoattenuation with compression and detachment of the frontal lobes (14, 15). generally, most cases with pneumocephalus need conservative treatment. simple pneumocephalus with no neurological signs is treated by head elevation, administration of osmotic diuretics, analgesics and antipyretics, and also preventing manoeuvres that increase intracranial pressure such as the valsalva manoeuvre (2, 5). high concentration oxygen increases absorption of pneumocephalus. antibiotics are recommended if meningitis is suspected (3). in cases with tension pneumocephalus with substantial intracranial pressure, emergent decompression is indicated (2, 5, 16). once air is aspirated, closure of dural defect is the only certain way to prevent recurrence of tension pneumocephalus (8). this case had several important points worth discussing. the patient’s brain ct scan showed tension pneumocephalus with air-fluid level, which is extremely rare (17). the patient had no external lacerations after the initial trauma and reported no history of posttraumatic rhinorrhoea or otorrhoea. in this patient, tension pneumocephalus can probably be explained in the context of occult dural laceration fracture of the right frontal sinus and ethmoid sinus walls, which let air enter unilaterally (ball-valve mechanism). moreover, given the rare brain ct scan view and mild fever, an intracranial abscess (secondary to gas-forming organisms) is a highly important differential diagnosis, which explains why a broadspectrum antibiotic was administered for the patient until mri was performed. 4. conclusion delayed tension pneumocephalus is a neurosurgical emergency and a complication rarely seen after head trauma, which requires prompt surgical intervention. however, depending on size and severity of signs and symptoms some cases could be managed conservatively and with long-term follow-up. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e22 figure 1: spiral brain ct scan without contrast (axial cut) revealed air-fluid level in the frontal parenchyma with midline shift and compression effect on the anterior horn of the lateral ventricles in the right frontal lobe. figure 2: magnetic resonance imaging (mri) with contrast (axial, coronal and sagittal views) revealed no rim enhancement around the lesion, which ruled out brain abscess and confirmed tension hydropneumocephalus diagnosis. 5. declarations 5.1. acknowledgment we thank dr. mohammad fathi, neurosurgeon, who participated in case management. 5.2. authors’ contributions tm was the lead author for this case report leading the initial patient management and writing the manuscript with support from ms. em and pn supervised the project. 5.3. conflict of interest talayeh mirkarimi, mohammad salek, ehsan modirian and peyman namdar declare that they have no conflict of interest 5.4. funding and supports the authors received no financial support for authorship or publication of this article. 5.5. ethical consideration and patient’s consent written informed consent was obtained from the patient’s parent for publication of this case report and accompanying images. references 1. chhiber ss, nizami fa, kirmani ar, wani ma, bhat ar, zargar j, et al. delayed posttraumatic intraventricular tension pneumocephalus: case report. neurosurgery quarterly. 2011;21(2):128-32. 2. leong k, vijayananthan a, sia s, waran v. pneumocephalus: an uncommon finding in trauma. the medical journal of malaysia. 2008;63(3):256-8. 3. kankane vk, jaiswal g, gupta tk. posttraumatic delayed tension pneumocephalus: rare case with review of literature. asian journal of neurosurgery. 2016;11(4):343. 4. solomiichuk vo, lebed vo, drizhdov ki. posttraumatic delayed subdural tension pneumocephalus. surgical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. mirkarimi et al. 4 neurology international. 2013;4. 5. dabdoub cb, salas g, silveira edn, dabdoub cf. review of the management of pneumocephalus. surgical neurology international. 2015;6. 6. ihab z. pneumocephalus after surgical evacuation of chronic subdural hematoma: is it a serious complication? asian journal of neurosurgery. 2012;7(2):66. 7. pillai p, sharma r, mackenzie l, reilly ef, beery pr. traumatic tension pneumocephalus–two cases and comprehensive review of literature. international journal of critical illness and injury science. 2017;7(1):58. 8. wang a, solli e, carberry n, hillard v, tandon a. delayed tension pneumocephalus following gunshot wound to the head: a case report and review of the literature. case reports in surgery. 2016;2016. 9. komolafe e, faniran e. tension pneumocephalus-a rare but treatable cause of rapid neurological deterioration in traumatic brain injury. a case report. african journal of neurological sciences. 2010;29(2):88-91. 10. horowitz m. intracranial pneumocoele: an unusual complication following mastoid surgery. the journal of laryngology & otology. 1964;78(2):128-34. 11. aydoseli a, akcakaya mo, aras y, boyali o, unal of. emergency management of an acute tension pneumocephalus following ventriculoperitoneal shunt surgery for normal pressure hydrocephalus. turkish neurosurgery. 2013;23(4):564-7. 12. almezeiny ta, almarshad ma. delayed posttraumatic tension pneumocephalus: a rare case report and review of the literature. dr sulaiman al habib medical journal. 2020;2(1):1-3. 13. kuncz a, roos a, lujber l, haas d, al refai m. traumatic prepontine tension pneumocephalus–case report. ideggyogyaszati szemle. 2004;57(9-10):313-5. 14. michel sj. the mount fuji sign. radiology. 2004;232(2):449-50. 15. atalar mh. mount fuji sign in tension pneumocephalus. journal of emergency medicine case reports. 2009;4(3):121-2. 16. rao v, fredriksli o, gulati s. post-traumatic epidural tension pneumocephalus: a case report. journal of medical case reports. 2015;9(1):1-4. 17. kumanan t, sujanitha v, suganthan n. tension hydropneumocephalus. 2018. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2017; 5 (1): e2 or i g i n a l re s e a rc h ketorolac versus magnesium sulfate in migraine headache pain management; a preliminary study hossein delavar kasmaei1, marzieh amiri2∗, ahmed negida3, samaneh hajimollarabi4, nastaransadat mahdavi5 1. department of neurology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, shahid beheshti hospital, guilan university of medical sciences, anzali, iran. 3. faculty of medicine, zagazig university, zagazig, egypt. 4. faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 5. department of anesthesiology, torfeh hospital, shahid beheshti university of medical sciences, tehran, iran. received: november 2015; accepted: january 2016; published online: 8 january 2017 abstract: introduction: migraine is a common cause of emergency department (ed) visits. to date, there is no recommended drug of choice for pain management of these patients. in the present study, we aimed to evaluate the effectiveness of ketorolac and magnesium sulfate in this regard. methods: this is a cross-sectional study performed on all 18 60 year-old patients, visiting two different eds with complaint of moderate to severe migraine headache. patients were treated with 30 mg ketorolac in one hospital and 1 gram magnesium sulfate in the other. pain scores were assessed on arrival, 1 and 2 hours after drugs administration and quality of pain management was compared between two groups using spss 22. results: 70 patients with the mean age of 36.4 ± 11.4 years were enrolled (51.4% male). the two groups were similar regarding baseline characteristics (p > 0.05). the improvement in pain score in magnesium sulfate group was greater than ketorolac group after both one hour (6 vs 3; p < 0.001) and two hours (7 vs 5; p < 0.001). conclusion:it seems that both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the emergency department. magnesium sulfate was superior to ketorolac both one and two hours after drug administration. keywords: magnesium sulfate; ketorolac; migraine disorders; emergency service, hospital; pain management © copyright (2017) shahid beheshti university of medical sciences cite this article as: delavar kasmaei h, amiri m, negida a, hajimollarabi s, mahdavi n. ketorolac versus magnesium sulfate in migraine headache pain management; a preliminary study. emergency. 2017; 5 (1): e2. 1. introduction migraine is a disabling disorder and a common cause of emergency department (ed) visits (1, 2). migraine prevalence has been reported to be 12-20% in different populations (3). to date, various drugs such as opium, nonsteroidal anti-inflammatory drugs (nsaids), neuroleptics, and triptans have been used for treatment of migraine headaches in ed (4-7). numerous studies have been carried out to evaluate the effectiveness of above-mentioned drugs, but to date there is no recommended drug of choice for this purpose. ∗corresponding author: marzieh amiri; department of emergency medicine, shahid beheshti hospital, guilan university of medical sciences, anzali, iran. email:dr.marzieh.amiri@gmail.com tel: +989121955792 magnesium sulfate and nsaids such as ketorolac are among the common drugs used for migraine headache pain management (8-14). in the present study, we aimed to evaluate the effectiveness of ketorolac and magnesium sulfate in controlling migraine headaches in patients presented to ed. 2. materials and methods 2.1. study design and settings this is a cross-sectional study performed from april to october 2015 in emergency departments of imam hossein and shohadaye tajrish hospitals, tehran, iran, to compare the effectiveness of ketorolac and magnesium sulfate in migraine pain management. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. delavar kasmaeii et al. 2 2.2. ethical issues the protocol of the study was approved by the ethical committee of shahid beheshti university of medical sciences. the authors declare their adherence to ethical principles of helsinki declaration throughout this research. eligible patients were enrolled after signing informed consent form. 2.3. participant all 18 60 year-old patients, visiting the emergency department with complaint of moderate to severe headache were interviewed by the main investigators. they were included if compatible with the international headache society (ihs) criteria for common migraine and had a pain score more than 5 (based on visual analogue scale (vas)). patients with history of peptic ulcer disease, ischemic heart disease, inflammatory bowel disease, coagulopathy, renal or hepatic failure, history of recent major surgery, history of hypersensitivity to the studied drug, and hypertension, as well as pregnant or breastfeeding women were excluded. 2.4. studied groups patients in shohadaye tajrish hospital were treated with 30 milligrams ketorolac and those in imam hossein hospital with 1 gram magnesium sulfate. one of the investigators in each hospital assessed pain scores on arrival, 1 and 2 hours after drug administration, when plasma concentration reaches its peak level. patients, pain investigator, and data analyzer were blind to the administered treatment. 3 or more scores decrease in vas was considered as clinically significant pain management. 2.5. statistical analysis statistical analysis was performed using spss version 22. continuous variables were described as mean ± standard deviation, and categorical ones as median, interquartile range, frequency and percentage. mann-whitney u test and wilcoxon test were used to analyze differences in vas pain scores. p value < 0.05 was considered significant. 3. results seventy patients with the mean age of 36.4 ± 11.4 years were enrolled (51.4% male). baseline characteristics of patients in each group, as well as their vas scores at baseline, 1 hour, and 2 hours after drug administration are compared in table and figure 1. the improvement in vas pain score in magnesium sulfate group was greater than ketorolac group after both one hour (6 vs 3; p < 0.001) and two hours (7 vs 5; p < 0.001). figure 1: box plot comparing minimum, maximum, median and inter-quartile range of pain scores at baseline, 1 hour, and 2 hours after drug administration between ketorolac and magnesium sulfate groups (p < 0.001). 4. discussion based on data extracted from the current study, both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the ed. magnesium sulfate was superior to ketorolac one and also two hours after drug administration. these drugs have been studied in patients with migraine headache solely or in comparison with other drugs. however, searching in google scholar and pubmed database with ”ketorolac and magnesium sulfate and migraine” as keywords, did not find any article that compared these two with each other. the findings of the literature have yielded conflicting results. a paper review performed in 2000 on the effectiveness and safety of different therapies in migraine headache, revealed that magnesium sulfate needs to be studied in appropriate trials before a conclusions can be drawn. ketorolac performs a little better but has been shown to be inferior to other treatments (15). 15 years later in 2015, based on published literatures between 1998 and 2013, american headache society reported that both ketorolac and magnesium sulfate are probably effective for acute migraine treatment (level b evidence) (16). simultaneously, canadian headache society strongly recommended the use of ketorolac, based on a low level of evidence and weakly recommended against the use of magnesium sulfate, based on moderate-quality evidence (17). high quality papers that have been published recently in authentic journals, clarify the ambiguity surrounding this topic. the current study still cannot prove anything with high reliability; but can be considered as a pilot study for running further apthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e2 table 1: baseline characteristics of the patients in the two groups variables ketorolac magnesium sulfate p age; mean ± sd 36.9 ± 10.7 36.0 ± 12.5 0.73 gender; male number (%) 15 (42.9) 19 (54.3%) 0.33 analgesic consumption before arrival; number (%) 18 (51.4) 12 (34.3) 0.14 duration of analgesic consumption before arrival; mean ± sd (hour) 3.0 ± 2.08 3.4 ± 1.6 0.56 pain score on arrival; median (iqr) 8 (3) 8 (2) 0.15 pain score after 1 hour; median (iqr) 4 (4) 2 (2) <0.001 pain score after 2 hours; median (iqr) 3 (2) 0 (1) <0.001 sd: standard deviation, iqr: inter quartile range. propriate double blind randomized controlled trials. 5. conclusion it seems that both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the emergency department. magnesium sulfate was superior to ketorolac both one and two hours after drug administration. 6. appendix none 6.1. acknowledgements this study was a part of dr. samaneh hajimollarabi’s thesis as a general physician at shahid beheshti university of medical sciences, tehran, iran. we would like to express our special thanks to the staff of emergency department shohadaye tajrish and imam hossein hospital. 6.2. conflict of interest all authors declare that there is no conflict of interest in this study. 6.3. funding/ support all authors declare that this study was accomplished without any funding or support. 6.4. author’s contribution all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data collection and interpretation. references 1. lainez mj, garcia-casado a, gascon f. optimal management of severe nausea and vomiting in migraine: improving patient outcomes. patient related outcome measures. 2013;4:61. 2. baratloo a, negida a, el ashal g, behnaz n. intravenous caffeine for the treatment of acute migraine: a pilot study. journal of caffeine research. 2015. 3. friedman bw, grosberg bm. diagnosis and management of the primary headache disorders in the emergency department setting. emergency medicine clinics of north america. 2009;27(1):71-87. 4. demaagd g. the pharmacological management of migraine, part 2: preventative therapy. pharmacy and therapeutics. 2008;33(8):480. 5. friedman bw, kapoor a, friedman ms, hochberg ml, rowe bh. the relative efficacy of meperidine for the treatment of acute migraine: a meta-analysis of randomized controlled trials. annals of emergency medicine. 2008;52(6):705-13. 6. baratloo a, rouhipour a, forouzanfar mm, safari s, amiri m, negida a. the role of caffeine in pain management: a brief literature review. anesthesiology and pain medicine. 2015(inpress). 7. balbin jeb, nerenberg r, baratloo a, friedman bw. intravenous fluids for migraine: a post-hoc analysis of clinical trial data. the american journal of emergency medicine. 2015. 8. gelfand aa, goadsby pj. a neurologist’s guide to acute migraine therapy in the emergency room. the neurohospitalist. 2012;2(2):51-9. 9. rowe-jones jm, medcalf m, durham sr, richards dh, mackay is. functional endoscopic sinus surgery: 5 year follow up and results of a prospective, randomised, stratified, double-blind, placebo controlled study of postoperative fluticasone propionate aqueous nasal spray. rhinology. 2005;43(1):2-10. 10. alimohammadi h, baratloo a, abdalvand a, rouhipour a, safari s. effects of pain relief on arterial blood o2 saturation. trauma monthly. 2014;19(1). 11. kdemirkaya s, vural o, dora b, topcuoglu ma. efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. headache: the journal of head and face pain. 2001;41(2):171-7. 12. bigal m, bordini c, tepper s, speciali j. intravenous this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. delavar kasmaeii et al. 4 magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. a randomized, double-blind, placebo-controlled study. cephalalgia. 2002;22(5):345-53. 13. taggart e, doran s, kokotillo a, campbell s, villa-roel c, rowe bh. ketorolac in the treatment of acute migraine: a systematic review. headache: the journal of head and face pain. 2013;53(2):277-87. 14. baratloo a, amiri m, forouzanfar mm, hasani s, fouda s, negida a. efficacy measurement of ketorolac in reducing the severity of headache. journal of emergency practice and trauma. 2016;2(1):21-4. 15. kelly a-m. migraine: pharmacotherapy in the emergency department. journal of accident, emergency medicine. 2000;17(4):241-5. 16. marmura mj, silberstein sd, schwedt tj. the acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. headache: the journal of head and face pain. 2015;55(1):3-20. 17. orr sl, aube m, becker wj, davenport wj, dilli e, dodick d, et al. canadian headache society systematic review and recommendations on the treatment of migraine pain in emergency settings. cephalalgia. 2014:0333102414535997. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction materials and methods results discussion conclusion appendix references emergency. 2017; 5 (1): e26 or i g i n a l re s e a rc h ventilator-associated pneumonia and its responsible germs; an epidemiological study rama bozorgmehr1, vanousheh bahrani1, alireza fatemi2∗ 1. clinical research development unit, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. infectious diseases and tropical medicine research center, shahid beheshti university of medical sciences, tehran, iran. received: august 2016; accepted: october 2016; published online: 10 january 2017 abstract: introduction: ventilator-associated pneumonia (vap) is one of the most common hospital infections and a side effect of lengthy stay in intensive care unit (icu). considering the ever-changing pattern of common pathogens in infectious diseases and the raise in prevalence of hospital infections, the present study was designed aiming to determine the prevalence of vap and its bacterial causes. methods: in this cross-sectional study, the medical profiles of all the patients under mechanical ventilation, who had no symptoms of pneumonia at the time of intubation and developed new infiltration in chest radiography after 48 hours under mechanical ventilation along with at least 2 of the symptoms including fever, hypothermia, leukocytosis, leukopenia, or purulent discharge from the lungs, were evaluated. demographic data, clinical and laboratory findings, and final outcome of the patients were extracted from the patient’s clinical profile and reported using spss version 20 and descriptive statistics. results: 518 patients with the mean age of 62.3 ± 20.8 years were evaluated (50.9% female). mean time interval between intubation and showing symptoms was 10.89 ± 12.27 days. purulent discharges (100%), leukocytosis (71.9%), fever (49.1%), hypothermia (12.3%), and leukopenia (8.8%) were the most common clinical and laboratory symptoms and acinetobacter baumannii (31.58%) and klebsiella pneumoniae (29.82%) were the most common germs growing in sputum cultures. 19 (33.3%) cases of pan drug resistance (pdr) and 10 (17.5%) cases of extensive drug resistance (xdr) were seen. mortality due to vap was 78.9% and there was no significant correlation between age (p = 0.841), sex (p = 0.473), icu admission (p = 0.777), duration of hospitalization (p = 0.254), leukocytosis (p = 0.790), leukopenia (p = 0.952), fever (p = 0.171), hypothermia (p = 0.639), type of culture (p = 0.282), and type of antibiotic resistance (p = 0.066) with mortality. conclusion: prevalence of vap and its associated mortality were 11% and 78.9%, respectively. the most common symptoms and signs were purulent discharge, leukocytosis, and fever. acinetobacter baumannii and klebsiella pneumoniae were the most common germs in sputum cultures with 50% resistance to commonly used antibiotics. keywords: pneumonia, ventilator-associated; cross infection; drug resistance, microbial; intensive care units © copyright (2017) shahid beheshti university of medical sciences cite this article as: bozorgmehr r, bahrani v, fatemi a. ventilator-associated pneumonia and its responsible germs; an epidemiological study. emergency. 2017; 5(1): e26. 1. introduction t he respiratory infection caused by micro-aspiration of organisms, 48 hours after going under mechanical ventilation is called ventilator-associated pneumonia (vap) (1). pneumonia is one of the most common hospital infections and a side effect of long stay in the intensive care ∗corresponding author: alireza fatemi; infectious diseases and tropical medicine research center, koodakyar st., daneshjoo blv, velenjak, shahid chamran highway, tehran, iran. tel: +989128949858 email: dr_fatemi_alireza@yahoo.com unit (icu) (2). this problem has a prevalence of 16 to 78%, while infections of urinary tract or skin have a prevalence of 1 4% (2-6). due to the important role of antibiotic-resistant bacteria in these kinds of infection, with longer duration of hospital stay, the probability of mortality will rise (3, 7, 8). vapis the reason for increased length of stay in icu and is responsible for about 50% of antibiotic prescriptions in this unit. the risk of this infection has been reported to be 3% for each day of intubation during the first 5 days, 2% for each day during 5thto 10th day, and 1% after 10 days of intubation (9). among the most common germs responsible for vap are staphylococcus aureus, pseudomonas aeruginosa, klebsiella this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. bozorgmehr et al. 2 pneumoniae, and acinetobacter (4, 10). in a study on 107 patients under mechanical ventilation, prevalence of vap was calculated to be 28.54%, with pseudomonas aeruginosa, meticillin resistant staphylococcus aureus, klebsiella pneumoniae, and acinetobacter baumannii (6). in another study, the total rate of hospital pneumonia was found to be 26.2% and its mortality rate was estimated to be 78.8% (11). a study in shiraz, iran, also reported a 10.2% vap rate and acinetobacter baumannii as the most common responsible organism (12). 2 other studies reported prevalence of vap to be 21.6% and 16% in 2013 and 2014, respectively (13, 14). considering the changes in pattern of common pathogens in infectious diseases and raise in hospital infection rates shown in various studies, identifying the pathogens responsible for infections can be of great help in selecting the proper treatment for vap and is therefore a requirement and research priority all over the world. the importance of this issue is emphasized when we note that most of these patients have been intubated in emergency department and stayed there for a while. therefore, the present study aimed to determine the rate of vap and its bacterial causes. 2. methods 2.1. study design and setting the present study is a retrospective cross-sectional one carried out on patients under mechanical ventilation in icu or other departments of shohadaye tajrish hospital, tehran, iran, during 2014-2016, aiming to determine the prevalence of vap and its bacterial causes in these patients. protocol of this study was approved by the ethics committee of shahid beheshti university of medical sciences. the researchers adhered to confidentiality of patient data and declaration of helsinki principles. 2.2. participants all the patients that had no signs of pneumonia at the time of intubation who developed new infiltration in chest radiography after 48 hours of intubation along with at least 2 of the symptoms including fever, hypothermia, leukocytosis, leukopenia, or purulent discharge from the lungs were considered vap cases and included in the study. if the patients had pneumonia before going under ventilation or during the initial 48 hours or their clinical data were not available, they were excluded. no age or sex limitation was applied and the reason for intubation was not considered in exclusion criteria. consecutive sampling was used. 2.3. data gathering demographic data of the patients (age, sex, admission ward), results of blood cell count, smear and culture of respiratory secretions, type of microorganism that grow, antibiotic resistable 1: demographic and clinical data of studied patients variable number (%) age (year) 15 29.9 6 (11.32) 30 44.9 4 (7.55) 45 59.9 12 (22.64) 60 -74.9 15 (28.30) >75 16 (30.19) sex female 29 (50.88) male 28 (49.12) hospitalized in intensive care unit 21 (36.64) other departments 36 (63.16) fever yes 28 (49.12) no 29 (50.88) hypothermia yes 7 (12.28) no 50 (87.72) purulent discharge yes 57 (100) no 0 (0) leukocytosis yes 41 (71.93) no 16 (28.07) leukopenia yes 5 (8.77) no 52 (91.23) drug resistance pan drug resistance (pdr) 19 (65.52) extensive drug resistance (xdr) 10 (34.48) final outcome recovery 12 (21.05) death 45 (78.95) tance, clinical symptoms, chest radiography findings, computed tomography (ct) scan of lungs, if present, and final outcome of the patients were extracted from their medical profile and recorded in a checklist designed for this purpose. data were gathered by a senior resident of internal medicine and when in doubt, an infectious disease specialist or an internal medicine specialist was consulted. the findings of patients’ radiography were reported by the center’s radiologist or the pulmonologist in charge of patient management in icu. 2.4. statistical analysis required sample size for this study was calculated to be 456 cases considering the 5% probability of vap (3% for each day in the initial 5 days and 2% for each day 5-10 days after intubation), α = 5% and desired precision of 2% (15). finally, data were analyzed using spss version 20 and chi square and t-test. qualitative data were reported as percentage and frequency, and quantitative ones as mean ± standard deviation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e26 (sd). to evaluate the correlation between studied variables and final outcome (mortality) chi-square test was used. p < 0.05 was considered as significance level. 3. results 3.1. baseline characteristics 518 patients with the mean age of 62.3 ± 20.8 (range: 15 97) years underwent mechanical ventilation via orotracheal intubation during the study period (50.9% female). 57 (11%) of cases developed vap. demographic data, clinical symptoms, and laboratory findings of the studied patients are summarized in table 1. the highest frequency of patients belonged to ≥ 75 years age group (30.19%). mean time interval between intubation and showing symptoms was 10.89 ± 12.27 days (range: 2 – 80). only 21 (36.8%) patients were hospitalized in icu and others were admitted to other departments. purulent discharges with 100%, leukocytosis with 71.9%, fever with 49.1%, hypothermia with 12.3%, and leukopenia with 8.8% were the most common clinical and laboratory findings in the studied patients. 3.2. cultures tables 2 and 3 depict the most common germ growths in sputum culture and the results of antibiogram done for patients with vap. the most common germ growths belonged to acinetobacter baumannii with 31.58%, and klebsiella pneumoniae with 29.82%, respectively. rate of resistance to ciprofloxacin, doxycycline, cotrimoxazole, ceftazidime, and cefotaxime were reported to be more than 50%. finally, 19 (33.3%) cases of pan drug resistance (pdr) and 10 (17.5%) cases of extensive drug resistance (xdr) were reported. no significant correlation was detected between the type of germ growth in sputum culture and presence of pdr or xdr (p = 0.931). radiography of 100% of the patients included turbidity in 1 or multiple lobes. 3.3. outcome mortality due to vap in the present study was estimated to be 78.9% (45 cases). no significant correlation was seen between age (p = 0.841), sex (p = 0.473), icu admission (p = 0.777), duration of hospitalization (p = 0.254), leukocytosis (p = 0.790), leukopenia (p = 0.952), fever (p = 0.171), hypothermia (p = 0.639), type of culture (p = 0.282), and type of antibiotic resistance (p = 0.066) with mortality. 4. discussion based on our findings, prevalence of vap was 11% among the studied patients and mortality due to it was estimated to be 78.9%. the most common clinical and laboratory symptoms and signs of this type of pneumonia were purulent discharge, table 2: frequency of germs’ growth in studied patients’ sputum culture growing germ number (%) acinetobacter baumannii 18 (31.6) klebsiella pneumoniae 17 (29.8) enterobacteriaceae 7 (12.3) candida albicans 4 (7) pseudomonas aeruginosa 4 (7) staphylococcus aureus 3 (5.3) escherichia coli 2 (3.5) proteus mirabilis 1 (1.8) negative 1 (1.8) table 3: frequency of antibiotic resistance in studied patients type of antibiotic number (%) ciprofloxacin 42 (73.7) doxycycline 36 (63.2) cotrimoxazole 32 (56.1) ceftazidime 31 (54.4) cefotaxime 31 (54.4) meropenem 28 (49.1) imipenem 28 (49.1) amikacin 26 (45.6) clindamycin 22 (38.6) tobramycin 21 (35.1) cefepime 20 (31.8) colistin 18 (31.6) ampicillin sulbactam 13 (22.8) levofloxacin 9 (15.8) cephalexin 6 (10.5) piperacillin 6 (10.5) gentamicin 5 (8.8) ceftriaxone 4 (7) cefixime 3 (5.3) azithromycin 2 (3.5) ofloxacin 1 (1.8) leukocytosis, and fever. acinetobacter baumannii and klebsiella pneumonia were the most common germs growing in sputum cultures that showed resistance to commonly used antibiotics in more than 50% of cases. in a study by nadi et al. mean age of the population affected with pneumonia in 353 patients who were hospitalized in icu of be’sat and ekbatan hospitals, hamedan, iran, was 51.2 ± 21.9 years, only 36 (10.2%) of which were affected with vap (16). as mentioned before, health care providers should face a big challenge named hospital infections. in the united states, every year, an average of about 2 million people are affected with this kind of infection and 90000 die, which makes hospital infections the 5th most common cause of death in health centers (15). the most common hospital infections are reported to be respiratory (65%), urinary tract (17%), and blood (12%) infections (15). ventilator associated infections have the highest rate of mortality among hospital acquired infections, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. bozorgmehr et al. 4 90% of which occur during mechanical ventilation and 50% in the initial 4 days of going under mechanical ventilation (15). in 2009, it was estimated that vap increases days in need of ventilator by 9.6 days, length of stay in icu by 6.1 days, and hospitalization duration by 11.5 days, which inflicts physical and financial burdens on the patient and health care system (17). despite measures taken and recent advances in treatment, prevention, and management of pathogens associated with ventilator, pneumonia is still a major cause of death in hospitalized patients. since multi-drug resistant pathogens play a major role in vap, currently antibiotics that properly cover these pathogens are used. these antibiotics include 3rd or 4th generation of cephalosporin (ceftazidime, cefepime), îš-lactamase inhibitors (piperacillin, tazobactam), carbapenems (imipenem, meropenem) in combination with an aminoglycoside (gentamicin, tobramycin, amikacin) or an anti-peseudomonas fluoroquinolone (levofloxacin, ciprofloxacine) (15). in the present study, vap had a prevalence of 11% among patients under mechanical ventilation. this rate was reported to be 19% in icu of shahid beheshti hospital, kashan, iran, during 2009-2010. in that study, a significant correlation was found between age, glasgow coma scale, positioning patient’s head in 30 or more degrees, oral hygiene, and training the staff regarding infection control with hospital pneumonia; and continuous training of staff and taking complete and regular care of oral hygiene of patients under mechanical ventilation were recommended (18). in a study by chung et al., 77.3% of intubated patients admitted to icu had vap (19). in a similar study, klompas et al. reported the prevalence of vap to be 9.5% among 599 patients who were hospitalized in icu of a hospital in america (20). this difference in prevalence may be due to the method of care given, the skill and experience of nurses, adhering to standards and beds being physically standard, positioning of patient’s head, space between beds and their rate of occupation, use of gloves and gowns by staff, oral hygiene, prevention of stomach distension, and method of prophylactic antibiotic use. therefore, the higher the rate of standard treatments carried out for intubated patients, the lower the rate of pneumonia. in the present study, there was no significant difference between icu of departments (internal medicine and surgery) regarding incidence of pneumonia or final outcome of mortality. in a study in arak carried out in 2011, there was a significant difference between icu of internal medicine and surgery wards (21). in addition, in the klompas et al. study, prevalence of pneumonia was 33% in internal medicine ward and 61% in surgery wad. this difference might be due to more invasive procedures, catheterization, intubation duration, and higher length of stay in surgery ward compared to internal medicine ward (20). the most common pathogens extracted from patients in the present study were acinetobacter baumannii and klebsiella pneumoniae, while in another study the most common pathogens were acinetobacter, staphylococcus aureus, and pseudomonas aeruginosa (21). in 2 separate studies, common germs responsible for pneumonia were staphylococcus aureus, pseudomonas aeruginosa, klebsiella pneumoniae, andacinetobacter, which is somehow similar to the present study (4, 10). in addition, in pediatric icu, the most common germs in sputum of pneumonia patients were staphylococcus aureus, pseudomonas aeruginosa, and enterobacter (22). regarding resistance to antibiotics in this study, pathogens were resistant to ciprofloxacin, doxycycline, cotrimoxazole, ceftazidime, and cefotaxime more than 50%. in a similar study, acinetobacter had the most resistance to gentamicin and was most sensitive to imipenem (21). sadly, 78.9% of our studied patients died because of vap. in a study by zarinfar, 11.7% of the patient fully recovered, 18.3% were relatively better, 20% did not get better, and 50% died, which is lower than the rate in our study. as mentioned before, this might be due to the procedures done, method of intubation, physical health, positioning of patient’s head, and type of antibiotic prescribed (21). 5. limitation among the limitations of this study were its retrospective design and extracting data from patients’ medical profile, which increase the probability of losing some information due to careless profile recording. in addition, data regarding the underlying disease and cause of intubation were not considered, while they may play a role in increasing mortality due to ventilation. 6. conclusion based on our findings, prevalence of vap and its associated mortality were 11% and 78.9%, respectively. the most common symptoms and signs were purulent discharge, leukocytosis, and fever. acinetobacter baumannii and klebsiella pneumoniae were the most common germs in sputum cultures with 50% resistance to commonly used antibiotics. 7. appendix 7.1. acknowledgements this article is derivated from dr. vanoushe bahrani’s thesis for achieving her specialist degree in internal medicine. 7.2. author contribution all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data collection and interpretation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e26 7.3. funding/support none. 7.4. conflict of interest all authors declare that there is no conflict of interest in this study. references 1. nseir s, zerimech f, fournier c, lubret r, ramon p, durocher a, et al. continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients. american journal of respiratory and critical care medicine. 2011;184(9):1041-7. 2. chastre j, fagon j-y. ventilator-associated pneumonia. american journal of respiratory and critical care medicine. 2002;165(7):867-903. 3. valles j, mesalles e, mariscal d, del mar fernandez m, pena r, jimenez jl, et al. a 7-year study of severe hospital-acquired pneumonia requiring icu admission. intensive care 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19. chung dr, song j-h, kim sh, thamlikitkul v, huang s-g, wang h, et al. high prevalence of multidrugresistant nonfermenters in hospital-acquired pneumonia in asia. american journal of respiratory and critical care medicine. 2011;184(12):1409-17. 20. klompas m, kleinman k, khan y, evans rs, lloyd jf, stevenson k, et al. rapid and reproducible surveillance for ventilator-associated pneumonia. clinical infectious diseases. 2012;54(3):370-7. 21. zarinfar n, sharafkhah m, bayat b, sgharfarazi a, masoomehsoofian. epidemiological factors of ventilatorassociated pneumonia (vap) among icu patients in valiasr hospital of arak. 2012. iranian journal of infectious diseases and tropical medicine. 2014;19(64). 22. nateghian a, omrani a, alipour z, haerinejad m. causes of ventilator associated pneumonia in pediatrics icu. iranian south medical journal. 2016;19(1):98-105. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e33 or i g i n a l re s e a rc h resident productivity in the emergency department after implementation of an automated patient assignment system; a brief report christian rosenow1, sophia aguirre1, thomas polveroni1, zachary ginsberg1, jordan pollock1, stephen traub2, douglas rappaport3∗ 1. mayo clinic alix school of medicine, scottsdale, az, usa. 2. brown university, providence, ri, usa. 3. department of emergency medicine, mayo clinic, scottsdale, az, usa. received: february 2022; accepted: march 2022; published online: 30 april 2022 abstract: introduction: the clinical diversity of patients presenting to the emergency department (ed) allows emergency medicine (em) and non-em residents to sharpen their clinical skills. in most eds, residents self-assign patients at their discretion. our institution transitioned from a self-assignment-system to an automated-system, after which we sought to determine the productivity of our non-em residents compared to the previous system. methods: in this retrospective cross-sectional study, resident productivity was measured as number of patient visits per hour and per 8.5-hour shift before and after the implementation of an automated patient assignment system in emergency department. the automated-system assigns one patient at the start of the shift, another 30 minutes later, and one patient every hour thereafter, throughout the shift. results: 28 residents performed 406 total shifts prior to implementation and 14 residents performed 252 total shifts post-implementation. the average number of patient visits per hour significantly increased from 0.52 ± 0.18 (95% ci 0.45-0.59, iqr 0.430.60) to 0.82 ± 0.11 (95% ci 0.75-0.88, iqr 0.74-0.89) after implementation of our assignment system (p<0.00001; figure 1). additionally, the average number of patient visits per 8.5-hour shift significantly increased from 4.46 ± 1.53 (ci 3.86-5.05, iqr 3.66-5.08) to 6.52 ± 0.86 (ci 6.02-7.02, iqr 5.90-7.09) after the implementation of our system (p<0.00001; figure 1). conclusion: these findings warrant further evaluation of the impact of patient assignment systems on trainee education. keywords: emergency medicine; internship and residency; education, medical, graduate; efficiency; patient care; rotation; emergency service, hospital cite this article as: rosenow c, aguirre s, polveroni t, ginsberg z, pollock j, traub s, rappaport d. resident productivity in the emergency department after implementation of an automated patient assignment system; a brief report. arch acad emerg med. 2022; 10(1): e33. https://doi.org/10.22037/aaem.v10i1.1516. 1. introduction the emergency department’s (ed) diversity of clinical pathology and patient populations along with around the clock delivery of care provides learners with a unique opportunity for a comprehensive bedside learning experience. in the fast-paced environment of the ed, residents are frequently integral parts of healthcare delivery. there are few studies investigating resident productivity in the ed and ∗corresponding author: douglas rappaport; mayo clinic, 13400 east shea boulevard, scottsdale, az 85259; email: rappaport.douglas@mayo.edu, tel/fax: (413)313-4882, orcid: http://orcid.org/0000-0002-2097-7439. even less research specifically devoted to non-em resident productivity in the ed. one study found that resident productivity was not significantly linked to ed volume or time of the day, but rather resident productivity declined over the course of a shift (1). furthermore, jeanmonod et al. (2008) found that shorter shift lengths resulted in more patients evaluated per hour by second year residents (2). high-volume eds afford the opportunity for a more robust training experience (3). moreover, higher level residents with more experience in a fast-paced environment show greater productivity than new residents (4). many eds use a physician self-assignment system where physicians assign themselves directly to patients that they this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. rosenow et al. 2 want to see and do so at their own pace (5, 6). other eds have instituted automated assignment systems to algorithmically distribute patients. in one facility, the automated assignment system decreased median length of stay, decreased median arrival to provider time, and decreased patients leaving before being seen by a provider (5). in an additional study, the assignment system reduced time to physician assessment and increased patient satisfaction (7). while automated assignment systems have been shown to be effective for emergency physicians, to our knowledge, no previous study has investigated this automated assignment system with residents, either emergency medicine (em) or nonem. our study aims to investigate the effects of an automated patient assignment system on improving the productivity of non-em residents, who rotate at our ed as preliminary year in internal medicine (pgy-1) and pgy-1 transitional year residents. 2. methods 2.1. study design and setting in this retrospective cross-sectional study, resident productivity was measured as number of patient visits per hour and per 8.5-hour shift before and after the implementation of an automated patient assignment system in emergency department. this study was conducted in a 27-bed emergency department at a large tertiary care center located in an urban setting that sees approximately 50,000 patients a year, with minimal seasonal variation in volume. prior to implementation of the new patient assignment system, residents worked 11-hour shifts; following implementation, residents worked 8.5-hour shifts. alterations in shift length were made independent of this study on an institutional level. time of day and day of the week of shifts are variable and dependent on number of residents on service and availability of faculty, among other factors. our emergency department, at a tertiary care center, has no emergency medicine residents, but pgy-1 internal medicine and pgy-1 transitional year residents rotate for a period of four weeks in the ed. ed volume before and after implementation was consistent with historical trends. 2.2. data collection this study was exempted from institutional review board office, as a completely deidentified database was used to calculate the average number of patients seen per hour and per shift by each resident before and after implementation of the automated patient assignment system. we compared the number of patients visited before and after the implementation of the new automatic assignment system, which assigns one patient at the start of the resident’s shift, another patient 30 minutes later, and one patient every hour thereafter, until the resident finishes their 8.5-hour shift. all patients were included in the new assignment system and the algorithm did not account for patient acuity. therefore, resident physicians can be assigned multiple critical patients within these intervals but always have the support and back up of multiple different emergency medicine attending physicians. the previous, self-assignment system allowed residents to choose patients at their own pace with no requirement for assigning additional patients. as shift length varied between preand post-implementation groups, patients seen per shift in the pre-implementation group was calculated as patients per 8.5-hour shift based on their average patients visited per hour for the duration of their 11-hour shift. patient outcomes, time to disposition, and patient satisfaction were not assessed in this study. 2.3. statistical analysis data are presented as mean ± standard deviation. significance was determined using student’s t-test. all statistical analyses were performed using microsoft excel (microsoft corp., redmond, wa). 3. results our study examined 28 residents performing 406 total shifts prior to implementation. 14 residents performing 252 total shifts were included post-implementation. the average number of patient visits per hour significantly increased from 0.52 ± 0.18 (95% ci 0.45-0.59, iqr 0.43-0.60) to 0.82 ± 0.11 (95% ci 0.75-0.88, iqr 0.74-0.89) after implementation of our assignment system (p<0.00001; figure 1). additionally, the average number of patient visits per 8.5-hour shift significantly increased from 4.46 ± 1.53 (ci 3.86-5.05, iqr 3.66-5.08) to 6.52 ± 0.86 (ci 6.02-7.02, iqr 5.90-7.09) after implementation of our system (p<0.00001; figure 1). 4. discussion this study found that non-em residents’ productivity, measured as patient visits per hour and per 8.5-hour shift, increased after implementation of an automated electronic health record-based patient assignment system compared to a traditional self-assignment system. the implementation of this system is thought to increase productivity by reducing the ability of residents to avoid picking up less desirable or more complex patients, or delay discharge of patients so as not to pick up new patients later in the shift (6). residents saw approximately 1 additional patient per shift; extrapolated over a one-month, 18-shift rotation, this equates to 18 additional patient encounters over the course of the rotation. resident education is complex and in part hinges on the quantity and diversity of patient interactions, as well as feedthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e33 figure 1: box-and-whisker plots of the average patient visits per hour (left) and per 8.5-hour shifts (right) by residents in emergency department before and after implementing an automated patient assignment system. back from supervising physicians. the emergency department is an excellent location for non-em residents to care for a high volume of patients with the benefit of 24/7 attending physician oversight and presence. a natural progression is expected to occur as experience and responsibility increase as residents advance through their training. in the emergency setting, residents have been shown to take care of increasing numbers of patients while visiting patients with increasing complexity during their progression (4). additionally, a multivariate analysis of residents’ pace demonstrated that optimal productivity is obtained with consistent pace of patient assignment (8), as opposed to a rapid pace, which is hindered by increased variability as ed volume fluctuates. the automated assignment system ensures a set pace of patient assignment regardless of ed volume, eliminating bias when selecting patients. furthermore, it also ensures complete objectivity with regards to clinical diversity, as residents are unable to avoid chief complaints or clinical scenarios they feel uncomfortable assessing. given the randomness and objectivity of the patient assignment system, over the course of a rotation, residents will see a wide array of complaints and thus a diverse variety of pathologies in the emergency department. to our knowledge, only one other study has successfully demonstrated an increase in non-em residents’ productivity in the emergency setting. chakravarthy et al. (2015) utilized shift cards for residents’ documentation of their patient load to be signed off on by their supervising attending physician each shift (9). this resulted in a significant increase in the number of patients visited; however, it may not have a systemic framework to create long-term productivity change. 5. limitations this study was limited by the number of residents rotating through the ed, as our institution does not have em residents; however, our sample size was large enough to be adequately powered for statistical analysis. additionally, randomization to different assignment systems was unfeasible, as this change was institutionally implemented. however, all residents in the pre-implementation group had completed their rotation prior to the transition and all residents in the post-implementation group began their rotation following the transition. therefore, individuals could not act as their own controls. while resident post-graduate year was not delineated, there was an even proportion of pgy-1 and pgy-2 residents in each of the groups. we did not assess the time of day, month, and year when shifts were performed, and thus, cannot conclude that shift timing was identical across groups, as this may also impact productivity. additionally, residents worked shorter shifts postimplementation relative to their pre-implementation counterparts (8.5 hours vs. 11 hours, respectively), which was an institutional policy change. as such, resident productivity may have been affected by shortened shift length, as studies have found a negative correlation between shift length and resident productivity (2). 6. conclusion the associated increase in non-em residents’ productivity with the implementation of an automated assignment system warrants larger studies examining the impact of similar assignment systems on a large scale and in emergency medicine residency programs. we believe that this increase in productivity provides residents with a better learning experience and ultimately, better training. further studies are needed to confirm this educational benefit and to assess patient outcomes after implementation of such systems. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. rosenow et al. 4 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions all authors were substantially involved in conception and design, drafting and revision of the manuscript, final approval of the manuscript, and agree to be accountable for all aspects of the work, per icmje recommendations. 7.3. funding and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. conflict of interest the authors have no conflicts of interest to report. references 1. jeanmonod r, brook c, winther m, pathak s, boyd m. resident productivity as a function of emergency department volume, shift time of day, and cumulative time in the emergency department. am j emerg med. 2009;27(3):3139. 2. jeanmonod r, jeanmonod d, ngiam r. resident productivity: does shift length matter? am j emerg med. 2008;26(7):789-91. 3. shayne p, lin m, ufberg jw, ankel f, barringer k, morganedwards s, et al. the effect of emergency department crowding on education: blessing or curse? acad emerg med. 2009;16(1):76-82. 4. brennan df, silvestri s, sun jy, papa l. progression of emergency medicine resident productivity. acad emerg med. 2007;14(9):790-4. 5. traub sj, stewart cf, didehban r, bartley ac, saghafian s, smith vd, et al. emergency department rotational patient assignment. ann emerg med. 2016;67(2):206-15. 6. hodgson nr, traub sj. patient assignment models in the emergency department. emerg med clin north am. 2020;38(3):607-15. 7. patel pb, vinson dr. team assignment system: expediting emergency department care. ann emerg med. 2005;46(6):499-506. 8. joseph jw, novack v, wong ml, nathanson la, sanchez ld. do slow and steady residents win the race? modeling the effects of peak and overall resident productivity in the emergency department. j emerg med. 2017;53(2):252-9. 9. chakravarthy b, posadas e, ibrahim d, mcarthur k, osborn m, hoonpongsimanont w, et al. increasing offservice resident productivity while on their emergency department rotation using shift cards. j emerg med. 2015;48(4):499-505. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e62 or i g i n a l re s e a rc h fentanyl versus methadone in management of withdrawal syndrome in opioid addicted patients; a pilot clinical trial baharak najafi1, shahin shadnia1, hossein hassanian-moghaddam1,2, amir heydarian3, arezou mahdavinejad4, nasim zamani1,2∗ 1. department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. social determinants of health research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, loghman hakim hiospital, shahid beheshti university of medical sciences, tehran, iran. 4. toxicological research center, shahid beheshti university of medical sciences, tehran, iran. received: july 2021; accepted: august 2021; published online: 13 september 2021 abstract: introduction: the most effective treatment for withdrawal syndrome in opioid-dependent patients admitted to intensive care units (icus) remains unknown. this study aimed to compare fentanyl and methadone in this regard. methods: this prospective, single-blinded, controlled pilot study was conducted on opioid-dependent intubated patients admitted to the toxicology icu of loghman hakim hospital, tehran, iran, between august 2019 and august 2020. patients were alternately assigned to either fentanyl or methadone group after the initiation of their withdrawal syndrome. duration and alleviation of the withdrawal signs and symptoms, icu and hospital stay, development of complications, development of later signs/symptoms of withdrawal syndrome, and need for further administration of sedatives to treat agitation were then compared between these two groups. results: median age of the patients was 42 [interquartile range (iqr): 26, 56]. the two groups were similar in terms of the patients’ age (p = 0.92), sex (p = 0.632), primary simplified acute physiology score (saps) ii (p = 0.861), and clinical opiate withdrawal score (cows) before (p = 0.537) and 120 minutes after treatment (p = 0.136) with either methadone or fentanyl. the duration of intubation (p = 0.120), and icu stay (p = 0.572), were also similar between the two groups. the only factor that was significantly different between the two groups was the time needed for alleviation of the withdrawal signs and symptoms after the administration of the medication, which was significantly shorter in the methadone group (30 vs. 120 minutes, p = 0.007). conclusion: it seems that methadone treats the withdrawal signs and symptoms faster in dependent patients. however, these drugs are similarly powerful in controlling the withdrawal signs in these patients. keywords: methadone; fentanyl; substance withdrawal syndrome; drug therapy; intensive care units cite this article as: najafi b, shadnia s, hassanian-moghaddam h, heydarian a, mahdavinejad a, zamani n. fentanyl versus methadone in management of withdrawal syndrome in opioid addicted patients; a pilot clinical trial. arch acad emerg med. 2021; 9(1): e62. https://doi.org/10.22037/aaem.v9i1.1384. 1. introduction substance use disorder is a common problem although its prevalence in the inpatient setting is not well-defined. in 2012, it was estimated that 11% of adult hospitalizations involved substance use disorders; however, this is proba∗corresponding author: nasim zamani; department of clinical toxicology loghman hakim hopsital, south karegar street, tehran, iran. tel/fax: 00982155404241, email: nasim.zamani@gmail.com, orcids: https://orcid.org/0000-0002-2091-0197. bly an underestimation, considering the high frequency of underdiagnosis of substance use disorders (1). withdrawal syndrome is a major problem in opioid-dependent patients when they are admitted and stay at the hospital for a relatively long period of time, such as when they are admitted to intensive care units (icus) for any reason. in toxicology icus, the situation is even more complicated as the dependent patient has already overdosed on a substance or medication making the selection of the best drug/medication for treatment of withdrawal a challenge. different medications have been proposed as substitutes this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. najafi et al. 2 for opioids but it is generally accepted that the best drug/medication for treatment of withdrawal syndrome is the one the patient is dependent on (2). however, management of critically ill or injured patients who use illicit substances is complicated due to both the intoxicating and the withdrawal effects of those substances. on the other hand, some medications (including tramadol, oral methadone, opium tincture, etc.) are not available in hospital settings and this may complicate the process of treatment of withdrawal syndrome in dependent patients. the complex physiologic responses of these patients as well as their loss of consciousness during the withdrawal may further complicate their management (3). in addition, poor management of withdrawal syndrome may cause severe agitation, increase the need for sedation, postpone extubation, and increase the hospital stay. thus, finding the best medication to control withdrawal syndrome in dependent patients admitted to the icu is a major challenge, a fact that has been overlooked in the existing literature. the aim of the current study was to compare fentanyl, as a routinely administered drug in icus to control both withdrawal and pain, with methadone, as a widely accepted medication to treat withdrawal syndrome in hospitaladmitted opioid-dependent patients. 2. methods 2.1. study design and setting in a prospective, single-blinded, controlled pilot study, opioid-dependent intubated patients admitted to toxicology icu of loghman hakim hospital between august 2019 and august 2020 were alternately assigned to either fentanyl or methadone groups. the study was approved by our local ethics committee in shahid beheshti university of medical sciences under the code ir.sbmu.retech.rec.1398.457 and registered on iranian registry of clinical trials (irct: irct20150110020624n2). written consents were obtained from the patients’ relatives on icu admission 2.2. participants addicted patients who were intubated and their signs and symptoms of withdrawal initiated during icu stay were included. any severity of withdrawal symptoms was considered as the inclusion criteria (mild, moderate, and severe withdrawal symptoms). patients with other dependencies (such as dependency to benzodiazepines) were excluded. 2.3. interventions the patients were then alternately assigned to either methadone or fentanyl groups. only the patients were blinded to the type of treatment they were given as they were unconscious and intubated. in the methadone group, they were put on subcutaneous methadone (faran shimi company, iran) with the initial dose of 10 mg every 12 hours (20 mg/day) in the beginning. the dose was subsequently adjusted based on the patients’ withdrawal signs and symptoms. in the fentanyl group, the patients were put on intravenous administration of fentanyl (faran shimi company, iran) with the initial dose of 50-100 µg/hour, which was subsequently adjusted based on the patients’ response. the mean dose of fentanyl was considered for analysis. for instance, if a patient received fentanyl with the dose 50-100 µg/hour, a mean dose of 75 µg/hour was calculated and considered for analysis. half an hour and two hours later the patients were re-visited and their clinical opiate withdrawal score (cows) was re-calculated. clonidine was initiated and continued in all patients with the initial dose of 0.1 mg every eight hours (0.3 mg/day) and adjusted to a maximum daily dose of 1.2 mg. 2.4. data gathering demographic data and severity of symptoms as well as outcomes were recorded for all cases using a predesigned checklist. n.z was responsible for data gathering. 2.5. outcomes the primary outcome evaluated was alleviation of the withdrawal signs and symptoms. the secondary outcomes were duration of withdrawal syndrome, duration of icu and hospital stay, duration of intubation, development of later signs and symptoms of withdrawal syndrome, development of complications (bed sores, rhabdomyolysis, acute tubular necrosis, aspiration pneumonia, and acute respiratory distress syndrome [ards] due to prolonged intubation), and need for further administration of sedatives to treat agitation. addiction was confirmed via the history taken from the patients’ next of kin, positive urine tests, and initiation of clinical opiate withdrawal syndrome, which was determined using clinical opiate withdrawal scale (cows). on icu admission, simplified acute physiology score (saps) ii was calculated for all patients. after the signs and symptoms of withdrawal initiated, the patients’ cows was measured (4). 2.6. statistical analysis the data were recorded and transferred to statistical package for social sciences (spss) software version 20 and analyzed by application of mann-whitney u test for non-normally distributed quantitative variables and pearson chi-square for categorical variables. a p value less than 0.05 was considered to be statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e62 table 1: comparison of the study groups regarding the baseline characteristics and outcomes (n=56) variable methadone (n=28) fentanyl (n=28) p* age (year) 41 (26, 55) 44 (22, 57) 0.921 saps ii 29 (15, 36) 24 (17, 37) 0.861 cows at the time of withdrawal 18 (15, 21) 18 (13, 22) 0.537 cows 30 minutes after administration 6 (18, 21) 6 (4,13) 0.967 cows 120 minutes after administration 2 (1, 3) 0 (0, 3) 0.136 symptom after administration (minutes) 30 (30, 60) 120 (45,120) 0.008 midazolam (mg/hour) 30 (7, 50) 12 (5, 50) 0.427 clonidine (mg/day) 0.30 (0.30, 0.60) 0.60 (0.34, 0.60) 0.161 duration of intubation (day) 9 (4, 17) 5 (2, 9) 0.120 duration of icu stay (day) 10 (7, 14) 7 (6,14) 0.572 data are presented as median (interquartile range). *mann-whitney u test; saps: simplified acute physiology score; cows: clinical opiate withdrawal score; icu: intensive care unit. 3. results a total of 48 patients (24 in each group) were included. median age of the patients was 42 [interquartile range (iqr): 26, 56] (range: 17 to 69) years. the two groups were similar in terms of the patients’ age (p = 0.92), sex (p = 0.632), primary saps ii score (p = 0.861), and cows before (p = 0.537) and 120 minutes after (p = 0.136) treatment with either methadone or fentanyl (table 1). the duration of intubation, icu stay, and hospital stay were also similar between the two groups. the only factor that was significantly different between the two groups was the time needed for alleviation of the withdrawal signs and symptoms after the administration of the medication, which was significantly shorter in the methadone group (p=0.007). median [iqr] clonidine administered was 0.30 [0.30, 0.60] and 0.60 [0.34, 0.60] in methadone and fentanyl groups, respectively (p = 0.16). eighteen patients in the methadone groups and 22 patients in the fentanyl group developed some complication during their icu stay although this difference was statistically insignificant (p = 0.2). seven patients (5 in methadone and two in fentanyl group) died showing a non-significant difference between the two groups (p = 0.4). median [iqr] cows was 18 [15, 22] (range; 3 to 27) before the administration of methadone or fentanyl, which decreased to 6 [5, 11] (range: 1 to 18) and 6 [4, 13] (range: 0 to 22) thirty and 120 minutes after administration of methadone and fentanyl, respectively (p = 0.008). 4. discussion our results showed that application of methadone and fentanyl controlled the withdrawal signs and symptoms with similar long-term effects, complications, hospital stay, and final outcome. the only significant difference between the groups in our study was the time needed for the medications to take effect. patients in methadone group responded to methadone faster, although the severity of cows was the same between the two groups after treatment. opiate withdrawal occurs when opioid concentrations decrease in the central nervous system of tolerant individuals (5). the mainstay of treatment of withdrawal syndrome is replacing the opiate with an opioid with less chance of being abused. adrenergic agonists, such as clonidine, may also be required to gain control over vital functions. general resuscitation and supportive measures are necessary for treatment in any withdrawal syndrome. a thorough history of the patient’s substance use/abuse/abuse patterns should be obtained from the patient, if possible, or from the family. fentanyl is the preferred opioid used in many icus (6, 7) because of its potency and not inducing histamine release, resulting in a low risk of hemodynamic instability. however, the short duration of action of this medication often requires a continuous infusion making the weaning process more difficult (8). the use of continuous infusion sedation is associated with prolongation of mechanical ventilation and longer hospital and icu stays (9). introduction of long-acting opioids via enteral administration to prevent opioid withdrawal syndrome was first described in 1965 with the use of methadone for the rehabilitation of heroin users and has been practiced in the united states since 1970 (10). we could not find any study in the literature that compared methadone and fentanyl in alleviation of withdrawal syndrome in dependent patients. in a similar study that compared opium tincture and methadone for controlling withdrawal syndrome in icu-admitted dependent patients, it was concluded that a lower dose of methadone could better control the patients’ agitation (11). however, the authors claimed that the two drugs controlled the patients’ signs and symptoms fairly similar. we can claim the same because our patients showed similar results in the two groups, but received lower doses of methadone compared to the continthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. najafi et al. 4 uous infusions of fentanyl. however, it should be borne in mind that considering the equivalent doses of fentanyl and methadone, it seems that even the received doses were practically similar and methadone is only superior to fentanyl since it is administered twice a day and causes less drowsiness. 5. limitations most of our patients were methadone users. this may be a potential source of bias because it is generally considered that the best treatment for withdrawal syndrome is the same drug that has caused it. thus, it seems that in these patients, methadone has been a better substitute from the beginning. this is a potential limitation of the current study, which should be considered and taken into account in future studies in this regard. the limited number of studied cases is another limitation. future studies on more cases are warranted to further elucidate the superiority of methadone to fentanyl in dependent patients admitted to the icus. 6. conclusion methadone seems to treat the withdrawal signs and symptoms faster compared to fentanyl. however, these drugs seem to similarly control withdrawal signs. further doubleblinded, randomized studies with larger sample sizes are warranted to clearly determine superiority or similarity of these two medications in treatment of dependent patients in the icus. 7. declarations 7.1. acknowledgments none. 7.2. funding and supports this study was funded by shahid beheshti university of medical sciences. 7.3. author contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. ss gave the idea. bn, am, and ah collected the data. hhm analyzed the data. nz drafted and finalized the manuscript. 7.4. competing interest none. 7.5. consent for publication not applicable. 7.6. availability of data data is available upon request. references 1. heslin kc, elixhauser a, steiner ca. hospitalizations involving mental and substance use disorders among adults, 2012: statistical brief# 191. 2015. 2. organization wh. training manual for clinical guidelines for withdrawal management and treatment of drug dependence in closed settings: manila: who regional office for the western pacific; 2009. 3. donroe jh, tetrault jm. substance use, intoxication, and withdrawal in the critical care setting. critical care clinics. 2017;33(3):543-58. 4. nelson kl, stenehjem d, driscoll m, gilcrease gw. fatal statin-induced rhabdomyolysis by possible interaction with palbociclib. frontiers in oncology. 2017;7:150. 5. jenkins dh. substance abuse and withdrawal in the intensive care unit: contemporary issues. surgical clinics of north america. 2000;80(3):1033-53. 6. payen j-f, chanques g, mantz j, hercule c, auriant i, leguillou j-l, et al. current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. the journal of the american society of anesthesiologists. 2007;106(4):687-95. 7. salluh ji, dal-pizzol f, mello pv, friedman g, silva e, teles jmm, et al. delirium recognition and sedation practices in critically ill patients: a survey on the attitudes of 1015 brazilian critical care physicians. journal of critical care. 2009;24(4):556-62. 8. wanzuita r, poli-de-figueiredo lf, pfuetzenreiter f, cavalcanti ab, westphal ga. replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial. critical care. 2012;16(2):1-9. 9. kollef mh, levy nt, ahrens ts, schaiff r, prentice d, sherman g. the use of continuous iv sedation is associated with prolongation of mechanical ventilation. chest. 1998;114(2):541-8. 10. leshner ai. science-based views of drug addiction and its treatment. jama. 1999;282(14):1314-6. 11. sohrevardi sm, pournamdari m, salimi r, sarrafzadeh f, ahmadinejad m. comparing the efficacy of methadone and tincture of opium in controlling agitation caused by withdrawal syndrome in opium-addicted patients in the intensive care unit: a randomized trial study. addiction & health. 2020;12(2):69. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e40 or i g i n a l re s e a rc h awareness of iranian medical sciences students towards basic life support; a cross-sectional study meisam akhlaghdoust1,2, saeid safari1,2∗, poorya davoodi3, shaghayegh soleimani4, maryam khorasani4, fatemeh raoufizadeh4, hosna karimi5, elahe etesami5, zeynab hamzehloei4, seyedeh sara sadeghi4, ladan heidaresfahani4, tooba ebadi fard azar4, haniyeh afshari badrloo4 1. functional neurosurgery research center, shahid beheshti university of medical sciences, tehran, iran. 2. usern office, functional neurosurgery research center, shahid beheshti university of medical sciences, tehran, iran. 3. pars advanced and minimally invasive medical manners research center, pars hospital, iran university of medical sciences, tehran, iran. 4. islamic azad university, tehran medical sciences branch, tehran, iran 5. science and research branch, islamic azad university, tehran, iran. received: march 2021; accepted: april 2021; published online: 20 may 2021 abstract: introduction: augmentation of the number of trained basic life support (bls) providers can remarkably reduce the number of cardiac arrest victims. the aim of this study was to evaluate the level of bls awareness among students of medical sciences in iran. methods: this multicenter cross-sectional study was performed on medical students at the 4 major medical schools in tehran, the capital of iran, between jan 2018 and feb 2019, using convenience sampling method. the level of medical sciences students’ awareness of bls was measured using an international questionnaire. results: finally, 1210 students with the mean age of 21.2 ± 2.3 years completed the survey (79% female). 133 (10.9%) students had cpr experience and none had received any formal training. none of the responders could answer all questions correctly. the mean awareness score of participants was 11.93 ± 2.87 (range: 10.13 -17.25). the awareness score of participants was high in 49 (4.04 %) participants, moderate in 218 (18.01%), and low in 943 (77.93%) of studied cases. conclusion: based on the findings of this study, more than 70% of the studied medical sciences students obtained a low score on bls awareness. keywords: awareness; cardiopulmonary resuscitation; heart arrest; attitude cite this article as: akhlaghdoust m, safari s, davoodi p, soleimani s, khorasani m, raoufizadeh f, karimi h, etesami e, hamzehloei z, sadeghi s s, heidaresfahani l, ebadi fard azar t, afshari badrloo h. awareness of iranian medical sciences students towards basic life support; a cross-sectional study. arch acad emerg med. 2021; 9(1): e40. https://doi.org/10.22037/aaem.v9i1.1231. 1. introduction cardiac arrest is a fatal condition responsible for a large number of deaths in the modern world, and it has remained common worldwide (1–3). deaths caused by cardiac arrest can be prevented via simple maneuvers and skills most of the time (5). cardio-pulmonary resuscitation (cpr) is a life-saving and valuable technique that was invented back in 1960 (6); it is indeed a facile procedure that permits almost everyone to sustain life and decreases mortality up to 50% in golden minutes after cardiac and respiratory arrests (7,8). ∗corresponding author: saeid safari; functional neurosurgery research center, shahid beheshti university of medical sciences, tehran, iran. email: safari.s@sbmu.ac.ir, tel: +9822724211, orcid: https://orcid.org/0000-00025917-633x. based on the place in which a cardiac arrest takes place, it is divided into two categories of out-of-hospital cardiac arrest (ohca) and in-hospital cardiac arrest (ihca). ohca occurs approximately in 19-104 per 100,000 persons each year (0.019-0.104%), and 10% of them are said to be saved at the hospital (9). statics present that 350,000 people in europe die annually because of ohca (9). in the usa, ohca is responsible for 760,000 deaths per year (10). augmentation of the number of trained basic life support (bls) providers can remarkably reduce the number of cardiac arrest victims (16). therefore, many countries worldwide have integrated these topics into the curricula of their educational centers or even workplaces believing that any individual in the society should have sufficient knowledge and awareness to provide bls when needed (18). having this in mind, expectation from physicians and paramedical staff is this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. akhlaghdoust and et al. 2 naturally higher as their career requires this knowledge. this study aimed to evaluate the level of bls awareness among iranian medical sciences students studying in four major iranian medical schools. 2. methods 2.1. study design and participants this multicenter cross-sectional study was performed on medical students studying in the 4 major medical schools (tehran medical sciences of islamic azad university, tehran university of medical sciences, shahid beheshti university of medical sciences, and iran university of medical sciences) in tehran, the capital of iran, between jan 2018 and feb 2019, using convenience sampling method. the level of medical sciences students’ awareness of bls was measured using an international questionnaire. the study protocol was approved by ethics committee of iran university of medical sciences (ir.iums.rec.1399.1291). 2.2. participants being a student in one of the fields of medical sciences (medicine, nursing, and midwifery) was the inclusion criterion. there was not any sex or age limitation in this study. incomplete questionnaires were excluded (29 questionnaire). 2.3. data gathering demographic data, age, cpr experience, sex, educational status, and attendance of bls courses were collected using a checklist. in addition, an international questionnaire that measures the level of awareness about bls was used for evaluating the awareness level of participants regarding bls. we used the persian version of the international questionnaire measuring the awareness of participants regarding bls. this questionnaire was designed by özbilgin ş et.al. based on the latest version of aha guideline. the international questionnaire measuring awareness of bls has 20 multiple-choice questions and each question has 1 point (19). the range of scores of this questionnaire is 16-20 (high), 11-15 (moderate), and 0-10 (low). persian version of this questionnaire is validated by ziabari et al. 2019 (6). 2.4. statistical analysis a required sample size of 1210 participants, was calculated using rao soft software. for statistical analysis, spss software version 22 (spss inc. chicago, il, united states) was used. the findings were presented as mean ± standard deviation or frequency and percentage. table 1: baseline characteristics of studied participants variable total age (years) mean ± sd 21.2 ± 2.3 sex female 956 (79.1) male 254 (20.9) educational status medical student 643 (53.1) nursing student 296 (24.5) midwifery student 271 (22.4) experience of cpr yes 133 (11.0) no 1077 (89.0) attendance of bls courses yes 194 (16.1) no 1016 (83.9) data are presented as frequency (%). sd: standard deviation; bls: basic life support; cpr: cardiopulmonary resuscitation. 3. results finally, 1210 students with the mean age of 21.2 ± 2.3 years completed the survey (79% female). baseline characteristics of studied participants are presented in table 1. among the participants, 133 (10.9%) had cpr experience and none had received any formal training. table 2 shows the results of students’ responses to 20 questions regarding bls awareness. none of the responders could answer all questions correctly. the mean awareness score of participants was 11.93 ± 2.87 (range: 10.13 -17.25). the awareness score of participants was high in 49 (4.04 %) participants, moderate in 218 (18.01%), and low in 943 (77.93%) of studied cases. 4. discussion based on the findings of this study, more than 70% of the studied medical sciences students obtained a low score on bls awareness. nowadays, with the growth of cardiopulmonary diseases, the rate of cardiac arrest has been remarkably increasing (3-6). it is expected from a majority of community members to be efficiently aware of bls (especially cpr) (7). cpr is one of the essential skills that people of a society have to learn because it is a life-saving skill and can reduce the number of ohca victims (8). based on the reports, performing proper basic life support can reduce the mortality rate, especially in ohca (3-5, 7, 9). the findings in this cross-sectional study showed low awareness of bls among medical sciences students. about 90% of cases had no experience of cpr, and more than 95% of participants had no idea about safety, and they did not know what they have to do when someone lies unresponsive on the street. many people do not like to give mouth-to-mouth this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e40 table 2: answers to basic life support awareness questions question answer correct 1. what is the abbreviation of “bls”? basic life support 280 (23.1) 2. when you find someone unresponsive on the road, what will your first response be? (note: you are alone there) look for safety 149 (12.3) 3. if you confirm somebody is not responding to you even after shaking and shouting at him, what will be your immediate action? activate ems 436 (36.0) 4. what is the location for chest compression? mid chest 331 (27.4) 5. what is the location for chest compression in infants? one fingerbreadth above the nipple line 230 (19.0) 6. if you do not want to give mouth-to-mouth cpr, the following can be done except no cpr 137 (11.3) 7. how do you give rescue breathing in infants? mouth-to-mouth and nose 364 (30.0) 8. depth of compression in adults during cpr 1 to 1/2 inches 137 (11.3) 9. depth of compression in children during cpr 1/2 to 1/3 depth of chest 85 (7.0) 10. depth of compression in neonates during cpr 1/2 to 1/3 depth of chest 77 (6.4) 11. rate of chest compression in adults and children during cpr 100/min 184 (15.2) 12. ratio of cpr is (single rescuer in the adult) 30:2 179 (14.8) 13. in a newborn, the chest compression and ventilation ratio is 3:1 79 (6.5) 14. what does abbreviation aed stands for? automated external defibrillator 61 (5.0) 15. what does abbreviation ems stands for? emergency medical service 188 (15.5) 16. if you and your friend are having food in a canteen and suddenly your friend starts expressing symptoms of choking, what will be your first response? confirm foreign body aspiration by talking to him 401 (33.1) 17. you are witnessing an infant who suddenly started choking while he was playing with the toy, you have confirmed that he is unable to cry (or) cough, what will be your first response? back blows and chest compression of five cycles each, then open the mouth and remove foreign body only when it is seen 210 (17.4) 18. you are witnessing an adult unresponsive victim who has been submerged in fresh water and just removed from it. he has spontaneous breathing, but he is unresponsive. what is the first step? keep him in recovery position 85 (7.0) 19. you noticed that your colleague has suddenly developed slurring of speech and weakness of right upper limb. which one of the following can be done? possibly stroke, he may require thrombolysis, and hence activate emergency medical services 100 (8.3) 20. you notice a 50-year-old gentleman with retrosternal chest discomfort, profuse sweating, and vomiting. what is next? probably myocardial infarction, hence activate ems, give him an aspirin tablet, and allow him to rest 436 (36.0) cpr due to health issues. according to the guideline of the american heart association, if someone does not like to give mouth-to-mouth or is not able to do it, that person should carry out hands-only cpr (13). the results demonstrated that only 11.3% of participants knew it. based on these results, medical students’ awareness of bls is very low. samiha jarrah et al. had done research evaluating awareness and knowledge of bls, and the results were similar to our study (3). they explained that the rate of knowledge and awareness of bls is low. in another study, neha baduni et al. did a research on the knowledge and awareness of bls among dental practitioners (20). 104 persons had participated in their study, and results showed that none of them had complete awareness regarding bls. singh et al. conducted a survey among 241 dentists (16). approximately 53% of them had not participated in any course about cpr or bls. in our study, none of the responders could answer all questions correctly, and none had received any formal training. the awareness of bsl in infants and children was low among participants. only 7% of participants knew the correct depth of compression during cpr in children and 6.4% in neonates. since medical students make up the future of the country’s healthcare system, the results of this study should be taken seriously. this study has shown a need for supplementary bls training in curricula of iran’s medical universities. more comprehensive studies could be performed in the future by collaborating with other universities in iran to evaluate the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. akhlaghdoust and et al. 4 awareness of medical sciences students regarding bls. we suggest some new methods in medical students’ programs for teaching bls including: vr-based serious games, teaching bls to others, and reinforcing the students’ knowledge and awareness every year. 5. limitations our study has some limitations. one of them is that it was conducted only in the four medical universities in tehran and did not involve the whole country. this study only demonstrates and evaluates the awareness, and the knowledge and practice regarding bls was not evaluated in this study. the number of students who completed the survey is not enough to generalize the results to other medical schools in iran. 6. conclusion based on the findings of this study, more than 70% of the studied medical sciences students obtained a low score on bls awareness. 7. declarations 7.1. acknowledgments none. 7.2. author contribution all authors made substantial contributions, revised the manuscript, and approved the final version for publication. 7.3. funding sources the author(s) received no financial support for the research, authorship, and/or publication of this article. 7.4. conflict of interest none to declare. references 1. ghanem e, elgazar m, oweda k, tarek h, assaf f, elhusseny mwa, et al. awareness of basic life support among egyptian medical students; a cross-sectional study. emergency. 2018;6(1). 2. saquib sa, al-harthi hm, khoshhal aa, shaher aa, alshammari ab, khan a, et al. knowledge and attitude about basic life support and emergency medical services amongst healthcare interns in university hospitals: a cross-sectional study. emerg med int. 2019;2019. 3. jarrah s, judeh m, aburuz me. evaluation of public awareness, knowledge and attitudes towards basic life support: a cross-sectional study. bmc emerg med. 2018;18(1):1–7. 4. zaheer h, haque z. students’ corner-awareness about bls (cpr) among medical students: status and requirements. j pak med assoc. 2009;59(1):57. 5. vural m, koşar mf, kerimoglu o, kızkapan f, kahyaoğlu s, tuğrul s, et al. cardiopulmonary resuscitation knowledge among nursing students: a questionnaire study. anatol j cardiol. 2017;17(2):140. 6. ziabari smz, kasmaei vm, khoshgozaran l, shakiba m. continuous education of basic life support (bls) through social media; a quasi-experimental study. arch acad emerg med. 2019;7(1). 7. alanazi a, bin-hotan alm, alhalyabah h, alanazi a, al-oraibi s. community awareness about cardiopulmonary resuscitation among secondary school students in riyadh. world j med sci. 2013;8(3):186e9. 8. gravesteijn by, schluep m, voormolen dc, van der burgh ac, miranda ddr, hoeks se, et al. cost-effectiveness of extracorporeal cardiopulmonary resuscitation after inhospital cardiac arrest: a markov decision model. resuscitation. 2019;143:150–7. 9. duff jp, topjian a, berg md, chan m, haskell se, joyner jr bl, et al. 2018 american heart association focused update on pediatric advanced life support: an update to the american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2018;138(23):e731–9. 10. alimohammadzadeh k, akhlaghdoust m, bahrainian sa, mirzaei a. survey on mental health of iranian medical students: a cross-sectional study in islamic azad university. shiraz e-medical j. 2017;18(7). 11. sangamesh nc, vidya kc, pathi j, singh a. awareness, attitude, and knowledge of basic life support among medical, dental, and nursing faculties and students in the university hospital. j int soc prev community dent. 2017;7(4):161. 12. al-shamiri hm, al-maweri sa, shugaa-addin b, alaizari na, hunaish a. awareness of basic life support among saudi dental students and interns. eur j dent. 2017;11(4):521. 13. powers wj, rabinstein 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in basic life support. plos one. 2018;13(6):e0198918. 16. zaheer h, haque z. awareness about bls (cpr) among medical students: status and requirements. j pak med assoc. 2009;59(1):57–9. 17. al-turki ya, al-fraih ys, jalaly jb, al-maghlouth ia, alrashoudi fh, al-otaibi af, et al. knowledge and attitudes towards cardiopulmonary resuscitation among university students in riyadh, saudi arabia. saudi med j. 2008;29(9):1306–9. 18. alharbi mm, horaib yf, almutairi om, alsuaidan bh, alghoraibi ms, alhadeedi fh, et al. exploring the extent of knowledge of cpr skills among school teachers in riyadh, ksa. j taibah univ med sci. 2016;11(5):497–501. 19. ozbilgin s, akan m, hancı v, aygün c, kuvaki b. evaluation of public awareness, knowledge and attitudes about cardiopulmonary resuscitation: report of izmir. turk anesteziyoloji ve reanimasyon dern derg. 2015;43(6):396–405. 20. baduni n, prakash p, srivastava d, sanwal m, singh b. awareness of basic life support among dental practitioners. natl j maxillofac surg [internet]. 2014 [cited 2021 jan 31];5(1):19. available from: /pmc/articles/pmc4178349/?report=abstract 21. chen m, wang y, li x, hou l, wang y, liu j, et al. public knowledge and attitudes towards bystander cardiopulmonary resuscitation in china. biomed res int. 2017;2017. 22. abbas a, bukhari si, ahmad f. knowledge of first aid and basic life support amongst medical students: a comparison between trained and un-trained students. j pak med assoc. 2011;61(6):613–6. 23. irfan b, zahid i, khan ms, khan oaa, zaidi s, awan s, et al. current state of knowledge of basic life support in health professionals of the largest city in pakistan: a cross-sectional study. bmc health serv res. 2019;19(1):1–7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e67 or i g i n a l re s e a rc h red blood cell distribution width (rdw ) as a predictor of in-hospital mortality in covid-19 patients; a cross sectional study setareh jandaghian1, atefeh vaezi1, amirreza manteghinejad2, maryam nasirian3, golnaz vaseghi4, shaghayegh haghjooy javanmard1∗ 1. applied physiology research center, cardiovascular research institute, isfahan university of medical sciences, isfahan, iran. 2. cancer prevention research center, omid hospital, isfahan university of medical sciences, isfahan, iran. 3. epidemiology and biostatistics department, health school, infectious diseases and tropical medicine research center, isfahan university of medical sciences, isfahan, iran. 4. isfahan cardiovascular research center, cardiovascular research institute, isfahan university of medical sciences, isfahan, iran. received: august 2021; accepted: september 2021; published online: 13 october 2021 abstract: introduction: red blood cell distribution width (rdw ) has been introduced as a predictive factor for mortality in several critical illnesses and infectious diseases. this study aimed to assess the possible relationship between rdw on admission and covid-19 in-hospital mortality. methods: this cross-sectional study was performed using the isfahan covid-19 registry. adult confirmed cases of covid-19 admitted to four hospitals affiliated with isfahan university of medical sciences in iran were included. age, sex, o2 saturation, rdw on admission, intensive care unit admission, laboratory data, history of comorbidities, and hospital outcome were extracted from the registry. cox proportional hazard regression was used to study the independent association of rdw with mortality. results: 4152 patients with the mean age of 61.1 ± 16.97 years were included (56.2% male). 597 (14.4%) cases were admitted to intensive care unit (icu) and 477 (11.5%) cases died. the mortality rate of patients with normal and elevated rdw was 7.8% and 21.2%, respectively (or= 3.1, 95%ci: 2.6-3.8), which remained statistically significant after adjusting for age, o2 saturation, comorbidities, and icu admission (2.03, 95% ci: 1.68-2.44). moreover, elevated rdw mortality hazard ratio in patients who were not admitted to icu was higher than icu-admitted patients (3.10, 95% ci: 2.35-4.09 vs. 1.47, 95% ci: 1.15-1.88, respectively). conclusion: the results support the presence of an association between elevated rdw and mortality in patients with covid-19, especially those who were not admitted to icu. it seems that elevated rdw can be used as a predictor of mortality in covid-19 cases. keywords: covid-19; sars-cov-2; erythrocyte indices; severity of illness index; mortality cite this article as: jandaghian s, vaezi a, manteghinejad a, nasirian m, vaseghi g, haghjooy javanmard s. red blood cell distribution width (rdw ) as a predictor of in-hospital mortality in covid-19 patients; a cross sectional study. arch acad emerg med. 2021; 9(1): e67. https://doi.org/10.22037/aaem.v9i1.1325. 1. introduction the pandemic of coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 ∗corresponding author: shaghayegh haghjooy javanmard; department of physiology, applied physiology research center, cardiovascular research institute, isfahan university of medical sciences, hezar-jerib ave., isfahan, iran. email: sh_haghjoo@med.mui.ac.ir, tel: +98(31)36692836, orcid: http://orcid.org/0000-0002-3853-5006. setareh jandaghian and atefeh vaezi are co-first authors. (sars-cov-2) is the greatest challenge of the current century. as reported by who, by august 2021, covid-19 has infected more than 215 million cases and caused more than 4 million deaths leading to enormous demands for healthcare services worldwide (1). therefore, rapid, accurate, and early clinical assessment of the disease severity is vital. covid-19 would start with lung involvement in some cases, which could quickly turn to acute respiratory distress syndrome (ards) and multi-systemic involvement, including the hematopoietic system (2, 3). the extraordinary case fatality rate of 59% for severe cases (4) indicates the need for identifying accesthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. jandaghian et al. 2 sible laboratory markers for risk stratification and effective utilization of intensive care unit (icu) services. hematological abnormalities, which have been reported in patients with covid-19, are considered to be potential predictors of the outcome. since complete blood count (cbc) is an inexpensive and routine test with a short turnaround time, finding an independent cbc factor to predict the severity of the disease would be of great value (5). red blood cell distribution width (rdw ) is one of the parameters of cbc and reflects the extent of anisocytosis/ heterogeneity of circulating erythrocytes volume (6). rdw has been reported to be increased in patients with alcohol abuse, hemolytic anemia, iron and b12/folate deficiency, and thrombotic and inflammatory conditions and can even be an independent factor predicting mortality in sepsis (7-12). previous studies have shown that increased rdw is associated with mortality in patients with ards (13-15). a recent report has shown that the predictive capacity of rdw in predicting mortality is equal to sepsis-related organ failure assessment (sofa) and acute physiology and chronic health evaluation-ii (apache-ii) (16). a meta-analysis found that the severely ill and expired covid-19 patients had a significantly elevated rdw (17). few studies have assessed the differential role of rdw in predicting the clinical outcomes and the prognosis of the illness in severe vs. moderate covid-19 hospitalized patients (1820). however, the association of rdw with adverse prognosis in covid-19 has not been well-established. besides, there is no consensus regarding the optimum predictive cut-off for rdw. this study aimed to assess the possible relationship between rdw on admission and covid-19 in-hospital mortality. 2. methods 2.1. study design and setting this cross-sectional study was performed using the data of isfahan covid-19 registry (i-core), a registry designated to covid-19 patients who are admitted to hospitals of isfahan, iran. in i-core, demographic information, signs and symptoms of patients at the time of admission, laboratory data, and medications during the admission time are recorded. the design and methodology of icore have been previously published in detail (21). the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1399.1000) approved this study. helsinki statement was observed throughout the study, and all data were managed anonymously. 2.2. participants patients with a positive covid-19 reverse transcriptionpolymerase chain reaction (rt-pcr) test, who were older than 18 years and were registered on i-core from february 21st, 2020 to september 23rd, 2020 were included in this study. patients without any rdw test on admission were excluded from the study. 2.3. measurements age, sex (male, female), past medical history, o2 saturation on admission (93% and higher, lower than 93%), rdw, white blood cell (wbc), platelets (plt), red blood cell (rbc), hemoglobin (hb), mean corpuscular volume (mcv ) on admission, and icu admission were extracted from the registry. based on our current laboratory standards, rdw more than 14.5% was considered elevated. the age was considered both as a categorical and a continuous variable. comorbidities were defined based on the international statistical classification of disease and related health problems (tenth revision). mortality during hospitalization was the primary outcome of the study. the severity of the disease was defined according to the new coronavirus pneumonia prevention and control program (7th edition) published by the national health commission of china. critical patients were defined as those with any of the following factors: (i) the need for mechanical ventilation in case of respiratory failure, (ii) shock, (iii) icu admission due to simultaneous failure in another organ (22). 2.4. statistical analysis data were analyzed using statistical package of social science software (spss version 18.0, il, chicago, usa). mean ± standard deviation (sd) and frequency were used to report categorical and continuous variables, respectively. to compare the continuous and categorical variables between the survivor and non-survivor groups, independent t-test and chi-square were used, respectively. the odds ratio (or) of mortality for elevated rdw was calculated in each age group. cox proportional hazards regression was used to calculate the mortality hazard ratio (hr). variables with a significant association in the first analysis were entered as covariates in the final model. we performed a subgroup analysis to investigate the independent role of rdw as a predictive factor for mortality in severe and non-severe patients. a two-tailed p<0.05 was considered statistically significant. 3. results 3.1. patients’ baseline characteristics data of 4152 patients were extracted from i-core and analyzed retrospectively. the mean age (±sd) of the patients was 61.1 (±16.97) years (56.2% male). of 4152 patients, 477 (11.5%) expired during hospital admission. 597 (14.4%) cases were admitted to icu, 272 (45.5%) of which expired. the mean age of the discharged patients was lower than the exthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e67 table 1: comparing some demographic, clinical, and laboratory characteristics of survived and non-survived covid-19 cases variables mortality p-value no n = 3675 yes n = 477 age (year) mean ± sd 60.5 (16.81) 65.8 (17.47) <0.0001 sex, n (%) male 2063 (56.1) 271 (56.8) 0.7 female 1612 (43.9) 206 (43.2) o2 saturation <93%, n (%) on admission 2610 (71.0) 404 (84.7) <0.0001 rdw stratified by age group under 50 13.7 (1.90) 15.3 (2.60) <0.0001 50-59 13.7 (1.80) 15.4 (3.19) <0.0001 60-69 14.0 (1.92) 14.9 (2.56) 0.002 70-79 14.1 (1.80) 15.0 (2.77) 0.001 80 and higher 14.4 (1.91) 15.7 (2.60) <0.0001 hematologic findings wbc (×10*3 /µl) 7.8 (4.82) 8.3 (7.27) 0.1 plt (×10*3 /µl) 196.1 (82.06) 203.5 (92.09) 0.06 rbc (×10*6 /µl) 4.5 (0.75) 4.6 (0.72) 0.4 hemoglobin (g/dl) 13.2 (2.22) 13.3 (2.29) 0.4 mcv 89.0 (7.60) 89.2 (7.39) 0.5 rdw 13.9 (1.88) 15.3 (2.73) <0.0001 comorbidities, n (%) anemia 1253 (34.1) 158 (33.1) 0.6 cancer 85 (2.3) 22 (4.6) 0.003 cvd 812 (22.3) 151 (31.8) <0.0001 htn 1207 (34.2) 199 (42.8) <0.0001 diabetes 1013 (27.9) 188 (39.6) <0.0001 immunodeficiency diseases 15 (0.4) 3 (0.6) 0.45 non asthma respiratory diseases 281 (7.7) 63 (13.3) <0.0001 asthma 98 (2.7) 10 (2.1) 0.45 at least one comorbidity 2154 (59.2) 376 (79.2) <0.0001 icu admission, n (%) 325 (8.8) 272 (57.0) <0.0001 data were reported in mean (standard deviation; sd) or number (%). rdw: red blood cell distribution width; wbc: white blood cells; plt: platelets; rbc: red blood cells; mcv: mean corpuscular volume; cvd: cardiovascular disease; htn: hypertension; icu: intensive care unit; p-value <0.05 is considered statistically significant. table 2: relation between mortality rate (%) and elevated red blood cell distribution width (rdw ) stratified by age groups age (year) normal rdw elevated rdw* or† (95% ci‡) p-value total death total death < 50 841 44 (5.2) 238 47 (19.7) 4.4 (2.8-6.9) <0.0001 50-59 601 34 (5.7) 168 31 (18.5) 3.7 (2.2-6.3) <0.0001 60-69 649 51 (7.9) 224 36 (16.1) 2.2 (1.4-3.5) <0.0001 70-79 532 57 (10.7) 238 53 (22.3) 2.3 (1.5-3.6) <0.0001 ≥ 80 390 49 (12.6) 271 75 (27.7) 2.6 (1.7-3.9) <0.0001 total 3013 235 (7.8) 1139 242 (21.2) 3.1 (2.6-3.8) <0.0001 elevated rdw is considered as the rdw more than 14.5% on admission; data are presented as number (%). *rdw: red blood cell distribution width; †or: odds ratio of mortality; ‡ci: confidence interval. pired ones (p-value <0.001), but the difference between sex groups (male vs. female) was not statistically significant (p-value, 0.7). table 1 compares some demographic, clinical, and laboratory parameters between survived and nonsurvived cases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. jandaghian et al. 4 table 3: cox multivariate proportional hazard regression model fitted to the inpatient mortality of covid-19 patients variables b se (b) wald p hr†= exp (b) 95.0% ci lower upper age (years) 0.01 0.003 14.8 <0.0001 1.012 1.006 1.018 rdw* (>14.5%) 0.71 0.095 56.04 <0.0001 2.033 1.689 2.448 icu (yes) 1.96 .096 421.35 <0.0001 7.122 5.905 8.590 o2 sat (< 93%) 0.07 0.13 0.32 0.56 1.077 0.835 1.391 comorbidity(yes) 0.16 0.12 1.96 0.161 1.183 0.935 1.497 *rdw: red blood cell distribution width; †hr: hazard ratio; icu: intensive care unit; ci: confidence interval; o2 sat: o2 saturation. table 4: cox multivariate proportional hazard regression model fitted to the inpatient mortality of severe covid-19 patients variables b se (b) wald p hr= exp (b) 95.0% ci lower upper age (years) 0.015 0.004 14.32 <0.0001 1.016 1.007 1.024 rdw (>14.5%) 0.38 0.12 9.59 0.002 1.47 1.15 1.88 o2 sat (<93%) -0.28 0.16 3.16 0.07 0.75 0.54 1.03 comorbidity(yes) -0.10 0.15 0.46 0.49 0.89 0.65 1.22 rdw: red blood cell distribution width; hr: hazard ratio; icu: intensive care unit; ci: confidence interval; o2 sat: o2 saturation. table 5: cox multivariate proportional hazard regression model fitted to the inpatient mortality of non-severe covid-19 patients variables b se (b) wald p hr= exp (b) 95.0% ci lower upper age (years) 0.003 0.005 0.55 0.45 1.003 0.994 1.013 rdw (>14.5%) 1.13 0.14 64.14 <0.0001 3.10 2.35 4.09 o2 sat (<93%) 0.66 0.22 8.77 0.003 1.94 1.25 3.02 comorbidity(yes) 0.53 0.18 8.67 0.003 1.70 1.19 2.42 rdw: red blood cell distribution width; hr: hazard ratio; icu: intensive care unit; ci: confidence interval; o2 sat: o2 saturation. 3.2. rdw and mortality risk the mean (±sd) rdw amongst survivors was lower than expired patients (13.9 ± 1.88 vs. 15.3 ± 2.7, respectively; p-value <0.0001). the difference between the mean rdw amongst discharged and expired patients was also found to be significant in all age groups (table 1). the mortality rate of covid-19 patients who had an elevated rdw (greater than 14.5%) on admission was 21.2%, while those with normal rdw had a mortality rate of 7.8% (p-value <0.0001). the odds ratio of death for those with an elevated rdw was 3.1 (95% ci: 2.6-3.8). table 2 compares the mortality rate between elevated and normal rdw stratified by age groups. the or of mortality in all age groups was elevated significantly. the highest and lowest or for mortality considering elevated rdw compared to normal rdw was in the group of younger than 50 years (4.4, 95% ci: 2.8-6.9) and in the group of 60-69 years (2.2, 95% ci: 1.4-3.5), respectively. the hr of mortality for elevated rdw after adjustment for covariates was 2.03 (95% ci: 1.68 to 2.44, p-value < 0.0001; table 3). also, icu admission had a significant association with hospital mortality (hr: 7.1, 95% ci: 5.9 to 8.5, p-value <0.0001). 3.3. rdw and mortality risk considering the severity in the subgroup of severe disease, the result of cox proportional hazard regression analysis (table 4 and 5) showed a mortality hr of 1.47 (95% ci: 1.15-1.88; p-value: 0.002) for those with elevated rdw. age was also associated with mortality in severe cases with an hr of 1.01 (95% ci: 1.007-1.024; p-value <0.0001). in the subgroup of non-severe patients, the hr of mortality for elevated rdw compared to normal rdw was 3.10 (95% ci: 2.35-4.09; p-value < 0.0001). the association between o2 saturation on admission and comorbidities with mortality was also significant with a hazard ratio of 1.9 (95% ci: 1.23.0; p-value: 0.003) and 1.7 (95% ci: 1.1-2.4; p-value: 0.003), respectively. figure 1 illustrates the cumulative hazard ratio for mortality in patients with elevated and normal rdw on admission in severe and non-severe patients, respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e67 the cumulative hr for elevated rdw was higher than normal rdw, after adjustment for age, o2 saturation at admission, and having any comorbidity. this difference is more obvious in the group of non-severe patients. 4. discussion identifying patients at highest risk for severe disease is essential to facilitating early, aggressive intervention and managing local hospital resources to mitigate the critical care crises. in the current study, the possible association between elevated rdw on admission and mortality risk in covid-19 patients was assessed and as assumed, elevated rdw was associated with mortality in covid-19 patients. compared to other markers with a significant prognostic value in sars-cov2 infection, rdw has some advantages because of its capability to efficiently predict the risk of mortality in the general population and patients with sepsis, ards, pneumonia, and other respiratory tract infections (23-26). several pathophysiological mechanisms affect rbcs homeostasis and lead to an increase in rdw. hypoxemia associated with covid-19 is one of them, which induces erythropoietin (epo) release, as reported in several similar lung diseases (27, 28). the epo increases rbc formation rate and rbc volume, which increase rdw (29). inflammatory cytokines associated with inflammatory diseases also increase rdw (30, 31). likewise, inflammation can slow down the maturation of rbcs, leading to reticulocytosis and an increase in rdw (32). another possible mechanism could be an overstimulation of the bone marrow following covid19 infection, which impacts rbc production, resulting in a broader range of rbc size and thus, elevated rdw levels (33). as shown by the results of our study, an elevated rdw at the time of admission in covid-19 patients is associated with a higher mortality rate (21.2% in patients with elevated rdw compared to 7.8% in patients with normal rdw ) in all age groups. in a similar study by foy bh et al. on 1641 covid19 patients, rdw greater than 14.5% was associated with a higher mortality rate (18); also, results of a study by hornick et al. show that each 1% increase in rdw is associated with a 39% increase in the mortality rate (34). as wang et al. stated, rdw was a prognostic predictor of illness severity in 98 covid-19 patients (35). in a prospective observational study on 143 cases, lorente et al. declared that nonsurviving covid-19 patients had higher rdw on icu admission with a higher mortality rate showing that rdw values greater than 13% have good performance in prediction of 30day mortality (16). the results of our study show that an elevated rdw (more than 14.5%) has a mortality hazard ratio of 1.47 in comparison to normal rdw. in a retrospective study on 225 hospitalized covid-19 patients in iran, rdw at the time of admission was neither related to mortality nor to icu admission; which can be of lower value compared to the results of our article since the sample population was larger in our study (36). our study also showed that elevated rdw is a stronger predictor of mortality in moderate covid-19 hospitalized patients compared to severe/critical cases. this may be due to the effect of different factors on rdw such as comorbidities, anemia, age, and inflammatory state. in line with our results, han et al. showed that rdw was able to predict all-cause mortality in those with critical illness, independent from severity scores (37). it is worth mentioning that rdw is usually a slow changing measure (18), so large increase in the non-severe patient group may propose a longer duration of disease for these patients at the time of admission, but accurate measurement in the earlier phases of the disease is required to test this assumption. as for other assessed parameters besides rdw elevation, modeling shows a negligible association between age and mortality with an hr of 1.01, while the association of elevated rdw with mortality is obvious in all age groups. as reported in a meta-analysis, the most significant increase in mortality risk was observed in patients aged 60 to 69 years (38). in contrast to age, patients’ sex did not seem to affect the mortality in our study; yet, in a cohort of 200 hospitalized patients with covid-19, male sex was associated with increased oxygenation requirements, higher in-hospital mortality, and worse hospital outcomes (39). other studies have also identified male sex as a risk factor for worse outcomes and increased mortality (40, 41). o2 saturation status on admission is another parameter associated with the mortality rate in covid-19 patients. in an observational study by jain et al., oxygen saturation below 93% (with or without supplemental support) was known as an important early marker or predictor of in-hospital death (or= 17.68) (42). the results of our study show a weak association between o2 saturation of less than 93% with mortality in non-severe patients; this is while it had no significant association with mortality in icu patients. this difference could be due to the level of o2 saturation, which is much lower in all icu patients, and the cut-off of 93% could not differentiate poor outcome patients. previous reports have shown a correlation between rdw and inflammatory cytokines such as tumor necrosis factor (tnf)alpha, interleukin (il)-1 and il-6, and between rdw and oxidative stress (1616). it can be speculated that the association between rdw and comorbid disorder in our study could be due to a higher degree of inflammation and oxidative stress in patients with cardiovascular disease, diabetes, cancer, and hypertension. rdw is a valuable laboratory parameter for predicting mortality, especially in patients without icu admission. it is suggested to check rdw on admission and consider its elevation as a predictor of poor outcomes. this indicator could be used as a criterion to prioritize patients for early and aggressive inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. jandaghian et al. 6 figure 1: mortality hazard ratio in patients with severe covid-19 (left) and non-severe cases (right), in patients with elevated and normal red blood cell distribution width (rdw ). age, o2 saturation on admission, and having any comorbidities were entered as covariates. rdw more than 14.5 was defined as elevated; event is defined as death; discharged patients were considered as censored. terventions, and better management of hospital resources. 5. limitations the main point of this study was to evaluate the potential value of rdw in risk stratification of covid-19 admitted patients in a large population based on a local covid-19 registry. since the analysis was limited to hospitalized patients, the results may not be applied to non-hospitalized infected individuals. moreover, the absence of d-dimer and bmi in our data is another limitation of our study. rdw changes were not followed during patients’ hospitalization, which is another limitation in this article. regarding all stated limitations, more studies are needed in the field of the current study. 6. conclusion the results support the presence of an association between elevated rdw and mortality in patients with covid-19, especially those who were not admitted to icu. it seems that elevated rdw could be used as a predictor of mortality in covid-19 cases. 7. declarations 7.1. acknowledgments the authors wish to thank mrs. azam mosayebi for her assistance during data gathering and other associated healthcare providers and hospital staff for their selfless services and cooperations during covid-19. 7.2. funding this research was supported by the isfahan university of medical sciences. 7.3. conflict of interest statement the authors declare no conflict of interest. 7.4. author contribution sh, gv, av, and sj performed the study concept and design. am was involved in data acquisition. av and mn performed the statistical analysis. sh, av, and sj performed data analysis and interpretation. sh, av, sj, and am wrote the first draft of the manuscript. all authors contributed to the critical revision and final approval of this manuscript. 7.5. data presentation the information of this manuscript has not been presented in any meeting(s). references 1. world health organization (covid-19) dashboard, available from https://covid19.who.int/ [access date: 28 august 2021]. 2. wang c, deng r, gou l, et al. preliminary study to identify severe from moderate cases of covid-19 using combined hematology parameters. annals of translational medicine. 2020;8(9): 593. 3. wiersinga wj, rhodes a, cheng ac, peacock sj, prescott hc. pathophysiology, transmission, diagnosis, and treatthis open-access article distributed under the terms of the creative commons attribution noncommercial 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intensive care unit. clinica chimica acta. 2018;487:112-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e24 https://doi.org/10.22037/aaem.v9i1.1096 rev i ew art i c l e the value of lactate dehydrogenase in predicting rhabdomyolysis-induced acute renal failure; a narrative review hazhir heidari beigvand1, kamran heidari2, behrooz hashemi3, amin saberinia3,4∗ 1. preventive medicine and public health research center, psychosocial health research institute, community and family medicine department, school of medicine, iran university of medical sciences, tehran, iran. 2. skull base research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. emergency department, bahonar hospital, faculty of medicine, kerman university of medical sciences, kerman, iran. received: january 2021; accepted: february 2021; published online: 9 march 2021 abstract: introduction: determining the diagnostic value of available biomarkers in predicting rhabdomyolysis-induced acute kidney injury (aki) is a priority. this study aimed to review the current evidence about the value of lactate dehydrogenase (ldh) in this regard. methods: in this narrative review, the papers in pubmed, embase, and web of science were studied. the keywords prognosis, prognoses, prognostic, ldh, rhabdomyolysis, emergency patients, and acute kidney failure or aki had been selected from mesh medical dictionary. related papers written in english and published from november 2007 to december 2020 were selected. results: finally, 14 articles were accepted for analysis. among the selected articles, four were randomized clinical trials, seven were crosssectional, and three were case-control studies. the results of the present review showed that abuse of illegal drugs is the most common cause of rhabdomyolysis. aki is the most serious complication of rhabdomyolysis reported in the studies. these studies have shown a three-fold increase in aki following drug-induced rhabdomyolysis. the review of the included articles shows that high ldh can predicts aki, especially in critical and emergency situations such as rhabdomyolysis where there is a risk of death if diagnosed late. these studies show that ldh increases in the presence of renal failure and tissue damage. conclusion: serum ldh is an appropriate and cost-effective prognostic indicator that can be used for risk classification of patients at risk for rhabdomyolysis-induced aki. keywords: l-lactate dehydrogenase; acute kidney injury; rhabdomyolysis; role; review; clinical enzyme tests cite this article as: heidari beigvand h, heidari k, hashemi b, saberinia a. the value of lactate dehydrogenase in predicting rhabdomyolysis-induced acute renal failure; a narrative review. arch acad emerg med. 2021; 9(1): e24. 1. introduction rhabdomyolysis accounts for 5 to 25% of all acute kidney injuries (akis) (1). the overall mortality rate of patients with rhabdomyolysis is about 10% but it is higher in men than women (2). rhabdomyolysis-induced aki can occur following poisoning, trauma, environmental factors, metabolic disorders, infections, immune disorders, and hereditary disor∗corresponding author: amin saberinia; emergency department, bahonar hospital, kerman university of medical sciences, kerman, iran. email: amin.saberinia@gmail.com, tel: +982122721155, orcid: http://orcid.org/0000-0001-8612-4319. ders (3, 4). it is also a major medical complication of disasters victims (5). considering the importance of early diagnosis of at-risk patients in emergency department, determining the diagnostic value of available biomarkers in predicting rhabdomyolysis induced aki is a priority (2, 6). muscle damage leads to membrane disruption, extracellular fluid leakage, and increased serum level of creatine phosphokinase (ck) and lactate dehydrogenase (ldh) enzymes (7-10). ldh levels are elevated in infarction, hepatocellular damage, carcinomas, and any conditions that cause cell necrosis (11, 12). various studies have evaluated the level of this enzyme at the time of kidney damage and have shown that in most cases, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. heidari beigvand et al. 2 very high concentrations of ldh have been observed in the serum of patients with rhabdomyolysis, which indicates that it can be useful in predicting renal failure (13, 14). based on the above-mentioned reasons, this study aimed to review the current evidence regarding the value of ldh in predicting the rhabdomyolysis induction aki. 2. methods 2.1. study design in this narrative review, the keywords prognosis, prognose, prognostic, lactate dehydrogenase (ldh), rhabdomyolysis, emergency patients, and acute kidney injury or acute renal failure had been selected from mesh medical dictionary. related papers written in english and published from november 2007 to december 2020 were searched in pubmed, embase, and web of science. original researches with available full text, which had evaluated the value of ldh in detection of at-risk patients for rhabdomyolysis-induced aki were selected. case reports, letters to the editors, and review papers were omitted. 2.2. search process and assessment of papers there was no restriction on duration of intervention, type of participants, and place of study. the steps for selecting the papers were as follows: first the initial search was performed by two researchers separately and the duplicate papers were removed, then with the aim of eliminating unrelated articles, the abstract and the title of each article were reviewed, potentially related papers meeting the inclusion criteria were identified. the full texts of the papers were reviewed by two authors and discussed until consensus was reached regarding their suitability. after compiling a list of study titles and abstracts in the databases, the strobe standard checklist was used to determine the quality of the studies. the strobe checklist consists of 22 different sections that assess various aspects of methodology including sampling methods, statistical analysis, confounding factor adjustment, measurement of variables, validity and reliability of the tools used, and the objectives of the study. 2.3. data extraction the specific characteristics of each study were extracted by the researchers using a standard form. two researchers examined the data independently, based on the inclusion criteria. in case of disagreement between the researchers, help was sought from a third researcher. the differences in findings were resolved using the method of benchmarking the overall conclusions of the articles and in this study, it was organized. findings on rhabdomyolysis, aki, and their association with lactate dehydrogenase were derived. 3. results 231 titles were extracted. in the initial screening stage, the title and type of articles were reviewed and finally 140 articles were excluded. then, the full text of the articles was studied and 50 articles were excluded due to differences in purpose. of the remaining 41 articles, 27 articles were excluded due to duplication of content and exclusion criteria, and finally, 14 articles were accepted for analysis (figure 1). the specifications and findings of the included articles are shown in table 1. among the selected articles, four were randomized clinical trials, seven were cross-sectional, and three were casecontrol studies. the studies, either specifically or generally, examined serum level condition and prognostic ability of ldh in predicting rhabdomyolysis-induced aki. amongst the fourteen articles, eight (three randomized clinical trials, two case-control, and three cross-sectional studies) reported a high serum level and prognostic value of ldh in kidney disease. the target groups were often 30-60 year-old individuals and a case-control study was conducted on rats. the results of the present review showed that abuse of illegal drugs is the most common cause of rhabdomyolysis. aki is the most serious complication of rhabdomyolysis reported in the studies (15-18). these studies have shown a three-fold increase in aki following drug-induced rhabdomyolysis (16). the review of the included articles shows that high ldh can predicts aki, especially in critical and emergency situations such as rhabdomyolysis where there is a risk of death if diagnosed late (15, 17-23). 4. discussion the studies showed that the serum level of ldh was high in patients with renal impairment and the concentration of this enzyme significantly increased in patients with rhabdomyolysis. studies have also shown that ldh can be useful in early diagnosis of acute renal failure in children. the exact process or processes of the development of rhabdomyolysis-induced aki are not yet clear. a number of proposed processes include mechanical damage to renal tubules caused by myoglobin deposition, and direct effect of the toxic property of free iron on renal tubules and volume depletion (15-18, 20, 21). the researchers reported that ldh levels significantly increased in acute renal failure, especially in conditions caused by rhabdomyolysis (15-18). understanding the cause of this increase can help in providing scientific solutions. tissue concentration of ldh is 500 times its serum concentration. in general, high concentrations of this enzyme are present in the liver, heart, red blood cells, skeletal muscles, and kidthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e24 neys (14). in cases of damage to the mentioned organs, such as in kidney and heart infarction and hemolysis, its serum levels rise. unlike enzymes such as aspartate transaminase (ast), alanine transaminase (alt), and creatine phosphokinase (cpk), which show significant variations in enzymatic activity between tissues, for ldh, the difference between the highest value tissues (such as the liver) and the lowest value tissues (such as the kidney) is only about 1.5 times (24). in the analysis of the reviewed studies, it can be concluded that serum ldh is an appropriate and cost-effective prognostic indicator that can be used for risk classification of patients with acute renal failure due to rhabdomyolysis. given the importance of rhabdomyolysis-induced acute renal failure, it is recommended that serum ldh level be measured at the time of admission to the emergency department and in the event of symptoms such as coma, convulsions, and elevated body temperature during the hours after hospitalization in order to promptly start treatment if rhabdomyolysis is proven. further understanding of the value of ldh in predicting rhabdomyolysis-induced aki could be the subject of more extensive research, as present studies in this area are limited to a small number of randomized controlled trials, case studies, and retrospective studies. we need to conduct more multi-centered studies to confirm the findings of the present review and deeply explore the mechanism. 5. conclusion the results showed that the level of ldh was high in patients with renal impairment and this enzyme significantly increased in patients with rhabdomyolysis. studies have also shown that ldh can be useful in early diagnosis of acute renal failure in children. 6. declarations 6.1. acknowledgement the authors would like to thank the shahid beheshti university of medical sciences for its technical and editorial assist. 6.2. funding none. 6.3. author contributions all authors met the criteria for authorship contribution based on the international committee of medical journal editors’ recommendations. 6.4. conflict of interest the authors declare that there is not any conflict of interest regarding this study. references 1. zutt r, van der kooi a, linthorst g, wanders r, de visser m. rhabdomyolysis: review of the literature. neuromuscular disorders. 2014;24(8):651-9. 2. safari s, yousefifard m, hashemi b, baratloo a, forouzanfar mm, rahmati f, et al. the value of serum creatine kinase in predicting the risk of rhabdomyolysisinduced acute kidney injury: a systematic review and meta-analysis. clinical and experimental nephrology. 2016;20(2):153-61. 3. packard k, price p, hanson a. antipsychotic use and the risk of rhabdomyolysis. journal of pharmacy practice. 2014;27(5):501-12. 4. omrani h, najafi i, bahrami k, najafi f, safari s. acute kidney injury following traumatic rhabdomyolysis in kermanshah earthquake victims; a cross-sectional study. the american journal of emergency medicine. 2020. 5. hosseini m, safari s, sharifi a, amini m, farokhi fr, sanadgol h, et al. wide spectrum of traumatic rhabdomyolysis in earthquake victims. acta medica iranica. 2009:459-64. 6. alavi-moghaddam m, safari s, najafi i, hosseini m. accuracy of urine dipstick in the detection of patients at risk for crush-induced rhabdomyolysis and acute kidney injury. european journal of emergency medicine. 2012;19(5):329-32. 7. duncan sj, howden cw. proton pump inhibitors and risk of rhabdomyolysis. drug safety. 2017;40(1):61-4. 8. mendes p, robles pg, mathur s. statin-induced rhabdomyolysis: a comprehensive review of case reports. physiotherapy canada. 2014;66(2):124-32. 9. nelson kl, stenehjem d, driscoll m, gilcrease gw. fatal statin-induced rhabdomyolysis by possible interaction with palbociclib. frontiers in oncology. 2017;7:150. 10. jin y, ye x, shao l, lin b, he c, zhang b, et al. serum lactic dehydrogenase strongly predicts survival in metastatic nasopharyngeal carcinoma treated with palliative chemotherapy. european journal of cancer. 2013;49(7):1619-26. 11. li b, li c, guo m, shang s, li x, xie p, et al. predictive value of ldh kinetics in bevacizumab treatment and survival of patients with advanced nsclc. oncotargets and therapy. 2018;11:6287. 12. chen z, guo q, lu t, lin s, zong j, zhan s, et al. pretreatment serum lactate dehydrogenase level as an independent prognostic factor of nasopharyngeal carcinoma in the intensity-modulated radiation therapy era. medical science monitor: international medical journal of experimental and clinical research. 2017;23:437. 13. wang y, li g, wan f, dai b, ye d. prognostic value of d-lactate dehydrogenase in patients with clear cell renal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. heidari beigvand et al. 4 cell carcinoma. oncology letters. 2018;16(1):866-74. 14. karamanos y. purification and characterisation of lactate dehydrogenase: an undergraduate biochemistry laboratory experiment. adv biochem. 2014;2(1):14-23. 15. åkerström b, rosenlöf l, hägerwall a, rutardottir s, ahlstedt j, johansson me, et al. ra1m-035, a physicochemically improved human recombinant α1-microglobulin, has therapeutic effects in rhabdomyolysis-induced acute kidney injury. antioxidants & redox signaling. 2019;30(4):489-504. 16. qingying f, liu r, fagui h, shan f, lu m. clinical analysis in patients with rhabdomyolysis and acute kidney injury caused by intense exercise. chinese journal of postgraduates of medicine. 2018;41(10):904-8. 17. green h, tobar a, gafter-gvili a, leibovici l, klein t, rahamimov r, et al. serum lactate dehydrogenase is elevated in ischemic acute tubular necrosis but not in acute rejection in kidney transplant patients. progress in transplantation. 2017;27(1):53-7. 18. nara a, yajima d, nagasawa s, abe h, hoshioka y, iwase h. evaluations of lipid peroxidation and inflammation in short-term glycerol-induced acute kidney injury in rats. clinical and experimental pharmacology and physiology. 2016;43(11):1080-6. 19. vikrant s, jaryal a, gupta d, parashar a. epidemiology and outcome of acute kidney injury due to venomous animals from a subtropical region of india. clinical toxicology. 2019;57(4):240-5. 20. nishimura h, enokida h, kawahira s, kagara i, hayami h, nakagawa m. acute kidney injury and rhabdomyolysis after protobothrops flavoviridis bite: a retrospective survey of 86 patients in a tertiary care center. the american journal of tropical medicine and hygiene. 2016;94(2):4749. 21. alzahri ms, mousa sa, almomen am, hasanato rm, polimeni jm, racz mj. lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease. saudi journal of kidney diseases and transplantation. 2015;26(6):1161. 22. bennett mr, nehus e, haffner c, ma q, devarajan p. pediatric reference ranges for acute kidney injury biomarkers. pediatric nephrology. 2015;30(4):677-85. 23. zager ra, johnson ac, becker k. renal cortical lactate dehydrogenase: a useful, accurate, quantitative marker of in vivo tubular injury and acute renal failure. plos one. 2013;8(6):e66776. 24. ma l, qiu j, zhang y, qiu t, wang b, chen w, et al. prognostic factors for operable biliary tract cancer: serum levels of lactate dehydrogenase, a strong association with survival. oncotargets and therapy. 2018;11:2533. 25. weide b, elsässer m, büttner p, pflugfelder a, leiter u, eigentler t, et al. serum markers lactate dehydrogenase and s100b predict independently disease outcome in melanoma patients with distant metastasis. british journal of cancer. 2012;107(3):422-8. 26. gurkan s, scarponi kj, hotchkiss h, savage b, drachtman r. lactate dehydrogenase as a predictor of kidney involvement in patients with sickle cell anemia. pediatric nephrology. 2010;25(10):2123-7. 27. mohammadi-karakani a, asgharzadeh-haghighi s, ghazi-khansari m, hosseini r. determination of urinary enzymes as a marker of early renal damage in diabetic patients. journal of clinical laboratory analysis. 2007;21(6):413-7. 28. huang c-c, lo h-c, huang h-h, kao w-f, yen dh-t, wang l-m, et al. ed presentations of acute renal infarction. the american journal of emergency medicine. 2007;25(2):164-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e24 table 1: characteristics and findings of included studies characters* title findings sanjay et al, 2019 (19). india, n = 181,clinical trial epidemiology and outcome of acute kidney injury due to venomous animals from a subtropical region of india compared to the survival group, serum white blood cells, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum albumin levels were significantly higher in patients who died. the proportion of patients with leukocytosis, hyperkalemia, metabolic acidosis, pneumonia / ards, seizures / encephalopathy, need for icu support, and dialysis was significantly higher in patients who died. akerstrom, et al, 2019 (15). sweden, n = 87, clinical trial ra1m-035, a physicochemically improved human recombinant α1-microglobulin, has therapeutic effects in rhabdomyolysis-induced acute kidney injury in this study, the researchers noted that lactate dehydrogenase levels show significant changes in acute renal failure due to rhabdomyolysis. qingying et al, 2018 (16). china, n = 22, cross sectional clinical analysis in patients with rhabdomyolysis and acute kidney injury caused by intense exercise there was a significant relationship between elevated serum ldh levels and acute renal failure. intense exercise in summer is likely to cause rhabdomyolysis and aki. early diagnosis and comprehensive treatment including appropriate blood purification are crucial for a successful treatment. the findings also emphasize the importance of age in muscle injury and the monitoring of electrolytes, markers of muscle damage and renal function for prevention of rhabdomyolysis and its related complications. hefziba et al, 2017 (17). israel, n = 150, cross sectional serum lactate dehydrogenase is elevated in ischemic acute tubular necrosis but not in acute rejection in kidney transplant patients a strong and statistically significant association between elevated serum ldh 1 to 3 days before renal biopsy and ischemic atn diagnosis after kidney transplantation was confirmed. akina et al, 2017 (18). japan, n = 59, case control evaluations of lipid peroxidation and inflammation in short-term glycerol-induced acute kidney injury in rats in this study, the researchers stated that there was a statistically significant relationship between time and serum ldh levels and acute renal failure. hiroak etal, 2016 (20). japan, n = 86, cross sectional acute kidney injury and rhabdomyolysis after protobothrops flavoviridis bite: a retrospective survey of 86 patients in a tertiary care center systolic blood pressure, serum creatinine, serum creatine kinase, that serum lactate dehydrogenase white blood cell count, and platelet count differed significantly between the aki and non-aki groups (p = 0.01) alzahri et al, 2015 (21), saudi arabia, n = 55, clinical trial lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease this study shows that in sickle cell patients ldh correlates with creatinine clearance and, therefore, ldh could serve as a biomarker to predict renal insufficiency in these patients. bennett et al, 2015 (22). usa, n = 368, clinical trial pediatric reference ranges for acute kidney injury biomarkers in this study, the researchers suggested that lactate dehydrogenase marker could be useful in early detection of acute renal failure in children. richard et al, 2013 (23). brazil, n = 45, case control renal cortical lactate dehydrogenase: a useful, accurate, quantitative marker of in vivo tubular injury and acute renal failure the results indicate that renal cortical ldh assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. the fact that it avoids the limitations of more traditional aki markers implies great potential utility in experimental studies, which require precise quantitation of tubule cell death. yue et al, 2013 (13). china, n = 192, cross sectional aims to evaluate the prognostic value of d lactate dehydrogenase in patients with kidney disease findings suggest that decreased ldhd expression may be a predictor of poor prognosis in patients with renal failure and even renal cancer. weide et al, 2013 (25). germany, n = 855, cross sectional serum markers lactate dehydrogenase and s100b predict independently disease outcome in melanoma patients with distant metastasis the researchers noted that changes in serum lactate dehydrogenase levels were useful as a marker in the prognosis of soft tissue disease, including kidney disease. in addition, complete metastasectomy has an independent prognosis specifically for the patient subgroup with normal ldh and s100b values. gurkan et al, 2010 (26). usa, n = 40, cross sectional aims to investigate lactate dehydrogenase as a predictor of kidney involvement in patients with sickle cell anemia multivariate analysis revealed a significant correlation between microalbuminuria and ldh level (p = 0.04) when controlled for age, sex, egfr, hemoglobin level, fetal hemoglobin%, type of sca, bmi, history of transfusions, and reticulocyte count. in this pediatric sca population, ldh was found to correlate with the presence of microalbuminuria and proteinuria. further studies are needed to confirm ldh as an early marker for the risk of kidney involvement among sca patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. heidari beigvand et al. 6 table 1: characteristics and findings of included studies characters* title findings mohammadi-karakani et al, 2007 (27). iran, n = 57, case control aim of urinary enzymes including ldh as an early marker of kidney injury in diabetic patients researchers have shown that ldh urine excretion can be useful in assessing renal failure patients with diabetes and confirmation of using ldh as a routine screening test. huang et al, 2007 (28). taiwan, n = 20, cross sectional the objective of the study was to investigate initial clinical characteristics that can suggest an early diagnosis of patients with acute renal infarction presenting with flank and/or abdominal pain in the emergency department (ed). there was a significant relationship between serum ldh and patient urine and renal infarction. this study, delineated specific clinical features for emergency physicians to raise their suspicion index for an early diagnosis of patients with renal infarction, a disease which is uncommon and is usually delayed or missed at initial ed presentation. *characters: authors, year, country, sample size, and type of study, respectively. ards: acute respiratory distress syndrome; icu: intensive care unit; ldh: lactate dehydrogenase; aki: acute kidney injury; ldhd: lactate dehydrogenase d; sca: sickle cell anemia; bmi: body mass index; egfr: estimated glomerular filtration rate; ed: emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e24 figure 1: flow diagram of the present meta-analysis; cvd: cardiovascular disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e46 or i g i n a l re s e a rc h effect of sofosbuvir on length of hospital stay in moderate covid-19 cases; a randomized controlled trial rama bozorgmehr1, farbod amiri2∗, mohammad hosein zadeh3, fariba ghorbani4, arash khameneh bagheri5, esmat yazdi3, sayyed mojtaba nekooghadam3, guitti pourdowlat6, alireza fatemi2 1. clinical research development unit, shohada-e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of internal medicine, shohada-e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. tracheal diseases research center, national research institute of tuberculosis and lung diseases, shahid beheshti university of medical sciences, tehran, iran. 5. department of radiology, shohada-e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 6. chronic respiratory diseases research center, national research institute of tuberculosis and lung disease (nritld), shahid beheshti university of medical sciences, tehran, iran. received: april 2022; accepted: may 2022; published online: 9 june 2022 abstract: introduction: efforts to control the covid-19 pandemic are still on. this study aimed to evaluate the effect of sofosbuvir on length of hospital stay and complications in covid-19 cases with moderate severity. methods: this randomized clinical trial was done on moderate covid-19 cases, who were admitted to shohadaye tajrish hospital, tehran, iran, from 4/2021 to 9/2021. eligible patients were randomly allocated into two groups of intervention (sofosbuvir) and control, and their outcomes were compared regarding the length of hospital stay and complications. results: 100 covid-19 cases were randomly divided into two groups of 50 patients, as the intervention and control groups. the mean age of patients was 50.56 ± 12.23 and 57.1±14.1 years in the intervention and control groups, respectively (p = 0.02). the two groups were similar regarding distribution of gender (p = 0.15), underlying diseases (p = 0.08), the severity of covid-19 (p = 0.80) at the time of admission, signs and symptoms (p > 0.05), and essential laboratory profile (p > 0.05). the length of hospital stay in the control and intervention groups was 7.7 ± 4.09 days and 4.7±1.6 days, respectively (p = 0.02). none of our patients needed icu or mechanical ventilation. conclusion: sofosbuvir may decrease the length of hospital stay of covid-19 cases with moderate severity, without a significant effect on the rate of intensive care unit (icu) need and mortality. keywords: sars-cov-2; treatment outcome; sofosbuvir; duration of therapy cite this article as: bozorgmehr r, amiri f, hosein zadeh m, ghorbani f, khameneh bagheri a, yazdi e, nekooghadam sm, pourdowlat g, fatemi a. effect of sofosbuvir on length of hospital stay in moderate covid-19 cases; a randomized controlled trial. arch acad emerg med. 2022; 10(1): e46. https://doi.org/10.22037/aaem.v10i1.1621. 1. introduction since the influenza pandemic in 1819, covid-19 has been one of the deadliest diseases we have ever faced. it has affected so many different aspects of human life, including health, economy, social life, schooling, travel, etc. (1). in∗corresponding author: farbod amiri; men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran, postal code:1989930002, email: farbod.amiri1996@gmail.com, orcid: http://orcid.org/0000-0002-8596-1948. troduction of the first vaccines against it in 2020 with their high efficacy, promised a near covid-19-free world (2). new variants, like delta and omicron, the different level of access to vaccine among different countries (3), and a variable acquired immunity among different individuals (4), especially immunocompromised patients (5), showed us that although vaccines are very effective, we are still far from an end to the pandemic. so, the need for a therapeutic alternative is still on. this need is more evident in times of covid-19 peaks, which put healthcare systems in danger of crash (6). one cheaper this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 2 and more scalable approach is repurposing the already available drugs (7). hepatitis c virus (hcv ) and severe acute respiratory syndrome coronavirus 2 (sars-cov-2) are both categorized as positive-sense ribonucleic acid (rna) viruses and have similar replication mechanisms. sovodac (fda approved) is standardly used to treat chronic hcv infection (8) and it functions by targeting the dependent rna polymerase enzyme (9). it is one of the antiviral drugs considered for treatment of covid-19and has been studied in different clinical trials (10). according to a study, which evaluated in vitro effecst of this medication on sars-cov-2, sofosbuvir could prevent rna synthesis via chain termination, and daclatasvir targets the folding process of secondary rna units in sarscov-2 (11). moreover, clinical trials (10) showed an association between lower mortality rates and the need for icu in covid-19 patients treated with sofosbuvir/daclatasvir (12). another aspect to consider is the financial burden of producing these drugs, in a nutshell, active ingredients for sofosbuvir and daclatasvir cost a reasonable amount of 700$/kg and 600$/kg, respectively. some studies suggest that sofosbuvir shows more affinity to mrna of the virus compared to daclatasvir, so the efficacy of each drug in treating covid-19 patients may be different (13-15). in terms of safety, in a randomized clinical trial (rct) with sofosbuvir/ledivaspir, no side effect leading to withdrawal from the study was reported (16). similarly, in another rct with sofosbuvir/daclatasvir, no severe side effects were reported (17). given sofosbuvir’s availability in iran, as well as it cost, efficacy, and safety background, we aimed to evaluate the effects of sofosbuvir alone (not in combination with any other drug) only in patients with moderate covid-19. 2. methods 2.1. study design and setting this randomized clinical trial was aimed to evaluate the safety and efficacy of sofosbuvir in management of moderate covid-19 cases, who were admitted to the covid-19 ward of shohadaye tajrish hospital, a tertiary teaching hospital in tehran, iran, from 4/2021 to 9/2021. eligible patients were randomly allocated to either the intervention or control group and their outcomes were compared regarding the length of hospital stay and complications. the ethics committee of shahid beheshti university of medical sciences approved the study protocol (ethics code: ir.sbmu.retech.rec.1399.1322). this trial was registered on the iranian registry of clinical trials (irct: irct20180302038915n1). all the patients were required to fill out the consent form to enter the trial. researchers adhered to ethical considerations of helsinki declaration and confidentiality of patients’ information. 2.2. participants confirmed covid-19 cases with ages ranging from 18 to 80 years, who were admitted to the hospital with at least one of the symptoms of: fever (oral temperature ≥ 38 °c), respiratory rate >24/minutes, 90%<o2saturation<93% in room air, or the pa02/fi02 ratio ≤ 300mghg were included in the study without gender limitation. covid-19 infection was confirmed using rt-pcr and spiral chest computed tomography (ct) scan. patients with moderate covid-19 were defined as cases with total severity score (tss)< 7 in the first 7 days of infection (18) and 90% < o2 saturation < 93% in room air on admission. patients with history of allergic reaction to the drugs used in this clinical trial, those who were pregnant or breastfeeding, former recipients of any experimental treatment for covid19, those with heart rate < 60/minutes, those currently on amiodarone as a treatment regimen, patients showing multiorgan failure evidence, needing mechanical ventilation, having estimated glomerular filtration rate < 50 milliliters per minute per 1.73 meters, admitted in intensive care unit (icu) ward, and those who were in shock were excluded. if one of these exclusion criteria occurred during the study, patients were pulled out immediately but included in the final analysis. 2.3. intervention eligible patients were randomly assigned to intervention or control group using block randomization (using a web service www.sealedenvelope.com). in this trial, the analyzer and care givers were blind to patients’ allocation group. the intervention group received interferon + sofosbuvir + national protocol for covid-19, and control group received interferon + national protocol for covid-19. interferon-beta 1a 44 micrograms (recigen, manufactured by cinnagen, from iran) was administered subcutaneously, one dose every other day for five doses for patients in both groups. sofosbuvir 400 mg/d for seven days (myhep, manufactured by mylan company, from india) was administered for intervention group. national protocol is an integrated flowchart for covid-19 diagnosis and treatment (19). 2.4. data gathering demographic information of patients, presenting signs/symptoms, vital signs, medical and drug history, and length of hospital stay were recorded at the time of admission in a pre-designed checklist. patients underwent daily assessments regarding the clinical course, disease progression, and laboratory and para-clinical tests during the hospitalization period. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e46 figure 1: flowchart of patients’ allocation. 2.5. outcome the primary outcome was defined as length of hospital stay (patients were discharged after improvement in the signs and symptoms, tachypnea, saturation o2, fever, which were assessed by a daily physical exam). patients were evaluated by experienced health providers every day during their hospital admission for clinical response to therapy, probable adverse effects, and complications according to the plan. 2.6. statistical analysis for statistical analysis, spss version 22.0 and stata 14.2 were used. shapiro-wilk and kolmogorov-smirnov tests were performed to evaluate the normal distribution of quantitative data. the baseline characteristics were compared using the chi-square test or one-way anova. quantitative data were presented as mean ± sd, and qualitative variables were expressed as number (percentages). the significance level was set at p < 0.05. mean difference was presented as effect size, and it was standardized using cohen’s d. 3. results 3.1. baseline characteristics of studied cases 100 covid-19 cases were randomly divided into two groups of 50 patients, as the intervention and control groups (figure 1). 25 (50%) patients in the control group and 19 (38%) in the intervention group were male (p = 0.15). the mean age of pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 4 table 1: comparing the baseline characteristics of studied cases between intervention (n = 50) and control (n = 50) groups variable intervention control p-value age (year) 50.56 ± 12.23 57.1 ± 14.1 0.04 gender male 25 (50.00) 19 (38.00) 0.20 female 25 (50.00) 31 (62.00) sign and symptom fever 25 (50.00) 19 (38.00) 0.20 chill 23 (46.00) 15 (30.00) 0.09 myalgia 21 (42.00) 19 (38.00) 0.50 rhinorrhea 2 (4.00) 2 (4.00) 0.60 cough 33 (66.00) 26 (52.00) 0.10 dyspnea 33 (66.00) 30 (60.00) 0.50 sore throat 1 (2.00) 0.50 chest pain 4 (8.00) 4 (8.00) 0.60 underlying disease diabetes mellitus 3 (6.00) 4 (16.00) 0.08 cardiac disorders 6 (12.00) 8 (16.00) complications gastrointestinal 24 (12) 20 (1) 0.60 disease severity tss 5.4 ± 2.0 5.6 ± 1.7 0.80 data are presented as mean ± standard deviation or frequency (%). tss: total severity score. table 2: comparing the laboratory findings between intervention (n = 50) and control (n = 50) groups parameter intervention control p-value ldh (u/i) 493 ± 181 469 ± 163.1 0.517 ferritin (mcg/l) 264.2 ± 228 316.2 ± 231 0.337 esr (mm/h) 31.9 ± 19.3 28.2 ± 20.1 0.361 crp (u/i) 33.1 ± 21.5 26.2 ± 23.8 0.137 hb (g/dl) 12.5 ± 1.5 12.5 ± 1.9 0.972 wbc (cells/mm3 ) 6000 ± 2600 8000 ± 4400 0.008 pmn (cells/mm3 ) 4600 ± 2200 7600 ± 1100 0.000 lymph (cells/mm3 ) 1300 ± 1200 1800 ± 1100 0.000 plt (cells/mm3 ) 178.1 ± 47.9 211 ± 66.3 0.007 alt (u/l) 34.3 ± 27.7 66.3 ± 19.2 0.098 ast (u/i) 39.4 ± 22.9 70.7 ± 27.6 0.254 alk-p (u/i) 201.2 ± 62.3 215 ± 114 0.470 cr (mg/dl) 1.1 ± 0.8 1.2 ± 0.8 0.420 bun (mg/dl) 16.8 ± 507 21.9 ± 16 0.041 data are presented as mean ± standard deviation. ldh: lactate dehydrogenase; esr: erythrocyte sedimentation rate; crp: c-reactive protein; hb: hemoglobin; wbc: white blood cell count; pmn: polymorphonuclear neutrophils; lymph: lymphocytes; plt: platelets; alt: alanine transaminase; ast: aspartate transaminase; alk-p: alkaline phosphatase; cr: creatinine; bun: blood urea nitrogen. tients was 50.56 ± 12.23 and 57.1±14.1 years in intervention and control groups, respectively (p = 0.02). the most common signs and symptoms were cough and dyspnea in both groups. tables 1 and 2 compare the baseline characteristics and presenting laboratory findings between two groups. the two groups were similar regarding distribution of underlying diseases (p = 0.08), the severity of covid-19 at the time of admission (p = 0.80), signs and symptoms (p > 0.05), and essential laboratory profile (p > 0.05). 3.2. outcomes the length of hospital stay in the control and intervention groups was 7.7 ± 4.09 days and 4.7±1.6 days, respectively (p = 0.02). none of our patients needed icu or mechanical ventilation or expired during our study. two patients from our control group required re-admission 14 days after discharge. one patient in the sofosbuvir group experienced nausea, so the medication was discontinued. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e46 4. discussion we intended to evaluate the safety and efficacy of sofosbuvir in cases with moderate covid-19. we concluded that sofosbuvir may decrease the length of hospital stay (lohs) but has no significant effect on the rate of intensive care unit (icu) need and mortality. eslami et al. study revealed that sofosbuvir/daclatasvir could decrease lohs, icu admission rate, and mortality in patients with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) (20). on the other hand, abbaspour kasgari et al. did not report any reduction in lohs with sofosbuvir/daclatasvir/ribavirin administration. limitations of their study include a small sample size (48 patients) (21). moreover, sayad et al. reported that sofosbuvir/velpatasvir did not improve mortality, icu admission, and lohs. the limitation of their study is lining up moderate and severe patients in one arm. they revealed that the severity can dramatically change the response to treatments (22). sofosbuvir in mild covid-19 could improve neither hospital admission rate nor lead to symptom alleviation (17). our study demonstrated that sofosbuvir could significantly reduce lohs, but it has no significant effect on icu admission and mortality rate. we suggest initiating treatment with sofosbuvir in moderate covid-19 to prevent exacerbation to severe infection. in this study, we answered if sofosbuvir alone is effective for covid-19 by focusing on moderate cases. more studies are required to determine the ideal time for starting this drug to achieve the most in terms of reaching clinical recovery sooner. 5. limitations this study has some limitations. we missed the opportunity to compare laboratory findings, especially inflammatory markers, before and after administering sofosbuvir due to the lack of consistency in available data. besides, we missed the opportunity of strengthening our methodology by using placebos and blinding; ethical issues and concern for patients’ survival were the most important barriers. 6. conclusion it seems that, sofosbuvir can decrease the length of hospital stay in cases with moderate covid-19 without having a significant effect on the rate of icu need and mortality. 7. declarations 7.1. acknowledgments we would like to thank dr. laya ohadi who helped us during this study and also the medical staff of the hospital’s covid19 ward who facilitated the interventions of the study. 7.2. data availability the data used in this study is available from the first author on reasonable request. 7.3. authors’ contributions all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. writing the first draft: rm revise: fa, mh data collection: ak, ez, sn data analysis: fg, af data interpretation: fg, gp design: fa 7.4. funding and supports no additional funding for the execution of the present study was received 7.5. conflict of interest the authors declare they have no conflict of interests references 1. baud d, qi x, nielsen-saines k, musso d, pomar l, favre g. real estimates of mortality following covid-19 infection. 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3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e30 or i g i n a l re s e a rc h factors associated with 24-hour clinical outcome of emergency patients; a cohort study kannika katsomboon1, siriorn sindhu2∗, ketsarin utriyaprasit2, chukiat viwatwongkasem3 1. dns candidate, faculty of nursing, mahidol university, thailand. 2. department of surgical nursing, faculty of nursing, mahidol university, thailand. 3. biostatistics department, faculty of public health, mahidol university, thailand. received: february 2022; accepted: march 2022; published online: 24 april 2022 abstract: introduction: pre-hospital and in-hospital emergency management play an important role in quality of care for emergency patients. this prospective cohort study aimed to determine factors associated with the 24-hour clinical outcome of emergency patients. methods: the sample included 1,630 patients, randomly selected through multi-stage stratified sampling from 13 hospitals in 13 provinces of thailand. data were collected during january-november 2018. clinical outcome was determined using pre-arrest sign score. data were analyzed via ordinal multivariate regression analysis. results: factors influencing 24-hour clinical outcome of emergency patients were age (or: 0.965; 95% ci: 0.96-0.97), having coronary vascular disease (cad) (or: 1.41; 95% ci: 1.05-1.88), and severity of illness based on rapid emergency medical score (rems) (or:1.09; 95% ci: 1.051.15). self-transportation and being transported by emergency medical service ambulance with non-advanced life support (ems-non-als) did not influence clinical outcome when compared to ems-als transport. being transported from a community hospital increased pre-arrest sign score 1.78 times when compared to ems-als (or: 1.78; 95% ci: 1.17-2.72). increased transportation distance increased the risk of poor clinical outcome (or: 1.01; 95% ci: 1.002-1.011). length of stay in emergency department (ed-los) more than 4 hours (or: 0.21; 95% ci: 0.15-0.29) and between 2-4 hours (or: 0.60; 95% ci: 0.47-0.75) decreased the risk of poor clinical outcome when compared to ed-los less than 2 hours. conclusion: having cad, severity of illness, increased transport distance, and ed-los less than 2 hours were found to negatively influence 24-hour clinical outcome of emergency patients. keywords: outcome assessment; health care; clinical decision rules; transportation of patients; patient care management; emergency treatment cite this article as: katsomboon k, sindhu s, utriyaprasit, viwatwongkasem c. factors associated with 24-hour clinical outcome of emergency patients; a cohort study. arch acad emerg med. 2022; 10(1): e30. https://doi.org/10.22037/aaem.v10i1.1590. 1. introduction pre-hospital emergency medical events are often associated with adverse clinical outcomes such as death or cardiopulmonary arrest. in bulgaria, overall mortality rate of emergency patients treated in emergency department (ed) was 2.4/ 100000 and 70.9% of deaths happened within 2.3 hour after arrival (1). in switzerland, the incidence of death in the emergency department (ed) was 2.6/1,000 (2). patientrelated factors, health provider-related factors and health ∗corresponding author: siriorn sindhu; faculty of nursing, mahidol university, bangkok, thailand. no. 2 wang lang road, siriraj, bangkoknoi, bangkok, 10700, thailand. email: siriorn.sin@mahidol.edu, tel/fax: +668-1817-6060, fax: +662-412-8415, orcid: http://orcid.org/0000-0001-9326-757x . service-related factors have been reported to affect immediate and intermediate outcomes of emergency services. age is one of the patient-related factors that contributes to mortality of emergency patients (1, 3). other patient-related factors contributing to mortality among emergency patients include poverty and late arrival to the hospital (1). emergency medical service (ems) systems play a very important role in improving the survival rates. pre-hospital transport time and distance has been found to influence emergency medical service outcomes (4-6). the roles of mode of transportation to ed on outcomes of emergency patients have been examined in previous studies. in france, no significant association between mode of transportation and allcause 30-day mortality was noted (4, 7). international literature reported conflicting results on effects of length of ed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. katsomboon et al. 2 stay (ed-los) on inpatient mortality (8-10). patient conditions on ed discharge, length of intensive care unit (icu) stay, and death were used as outcome indicators of emergency management in previous studies (8, 11). these outcomes may not fully reflect the quality of emergency medical service, especially when considering the relationship between pre-hospital emergency management, management in ed, and ongoing management in icu or inpatient wards following ed discharge. this study aimed to determine factors associated with 24-hour clinical outcome of emergency patients. 2. methods 2.1. study design and setting this prospective cohort study was conducted from january to november 2018 in 13 provincial hospitals in thailand. data from the national institute of emergency medicine service (niems, 2017) (12) was used for hospital selection. the provincial hospitals were classified into high volume (i.e., treating > 10,000 critical emergency patients/year), medium volume (i.e., treating between 4,00010,000 critical emergency patients/year), and low volume (i.e., treating < 4,000 critical emergency patients/year). there were 13, 33, and 31 high-, mediumand low-volume provincial hospitals, respectively. subsequent sampling by ratio yielded 3 highvolume hospitals, 5 medium-volume hospitals, and 5 lowvolume hospitals. the hospital samples totaled 13. the institutional review board, faculty of nursing, mahidol university (no: irb -ns2017/23.0409) approved this study for its human research ethics. the patients agreed to participate in this study and provided their consent. to comply with local requirements, additional ethics approvals were also sought from the 13 provincial hospitals before the commencement of the study. 2.2. participants the population included emergency patients who were managed in eds of provincial hospitals across thailand. the emergency patients in this study referred to those who were triaged as level-1 and level-2 based on emergency severity index or esi (version 4) (13). level-1 patients required immediate lifesaving interventions. level-2 patients were in a high-risk situation, confused or in severe pain or distress. we decided to include patients transported from community hospitals (i.e., inter-hospital transportation) because these patients experienced emergency episodes in their community, sought help in the ed of a nearby community hospital and were transported for definitive emergency care available at provincial hospitals. these patients were, therefore, considered emergency patients using pre-hospital and in-hospital emergency services. table 1: baseline characteristics of study participants variable value (n=1,630) age (year) mean ± sd 59.9 ±17.3 sex male 933 (57.2) female 697 (48.2) chief complaint respiratory 508 (31.2) neurological 415 (25.5) cardiovascular 310 (19.0) cardiopulmonary arrest 142 (8.7) trauma 116 (8.5) other** 139 (7.1) underlying disease hypertension 547 (33.6) coronary artery disease 309 (19.0) diabetes mellitus 148 (9.1) chronic obstructive pulmonary disease 121 (7.4) epilepsy 28 (1.7) none 34 (2.1) triage level esi level-1 546 (33.5) esi level-2 1084 (66.5) transportation distance (kilometers) mean ± sd 28.2 ±31.0 (1-224) mode of transportation self-transportation 722 (44.3) inter-hospital transfer 586 (35.9) ems – als 189 (11.6) ems-non-als 133 (8.2) severity of illness rems on triage 6.9 ± 3.5 (0-24) rems on discharge 5.7 ± 3.2 (0-24) length of stay in ed (minutes) mean ± sd 119.36± 131.7 (10-1505) ward admission general ward 1395(85.5) intensive care unit 164 (10.1) semi-intensive care unit 73 (4.4) clinical outcome based on pre-arrest sign no sign of cardiac arrest 146 (9) low risk of cardiac arrest 769 (47.2) moderate risk of cardiac arrest 322 (19.8) high risk of cardiac arrest 342 (21.0) severe risk of cardiac arrest 51 (3.1) data are presented as mean ± standard deviation (sd) or frequency (%). esi: emergency severity index; rems: rapid emergency medicine score; ems-als: emergency medical service ambulance with advanced life support. to be included in the study, patients had to be at least 18 years old and classified as level1 or level-2 in ed triage this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e30 figure 1: patient recruitment flowchart. ems-als: emergency medical service ambulance with advanced life support. table 2: univariate regression analysis of factors associated with 24-hour clinical outcome of patients admitted to emergency department (n=1,630) variable level of pre-arrest sign at 24 hours p no low moderate high severe age (year) mean ± sd 56.88±18.18 59.82±17.43 59.29±17.06 62.11±16.84 60.43±16.38 0.0331 sex male 81 (8.7) 449 (48.1) 194 (20.8) 180 (19.3) 29 (3.1) 0.313 female 65 (9.3) 320 (45.9) 128 (18.4) 162 (23.2) 22 (3.2) underlying disease hypertension 49 (9.0) 250 (45.7) 109 (19.9) 122 (22.3) 17 (3.1) diabetes mellitus 9 (6.1) 75 (50.7) 32 (21.6) 31 (20.9) 1 (0.7) coronary artery disease 2 (6.5) 17 (54.8) 4 (12.9) 7 (22.6) 1 (3.2) 0.0091 epilepsy 8 (9.5) 44 (52.4) 13 (15.5) 16 (9.0) 3 (3.6) copd 3 (12.5) 11 (45.8) 3 (12.5) 5 (20.8) 2 (8.3) none 22 (18.2) 52 (43.0) 21 (17.4) 25 (20.7) 1 (0.8) severity of illness rems at triage 5.64 ± 2.73 6.109 ± 3.13 7.37 ± 3.64 8.11 ± 3.55 10.61 ± 4.95 0.0001 rems at discharge 4.02 ± 2.57 4.94 ± 2.77 6.27 ± 3.17 6.89 ± 3.11 9.96 ± 5.25 0.0001 type of transportation inter-hospital 2 (0.3) 230 (39.2) 150 (25.6) 178 (30.3) 27 (4.6) 0.0001 self-transportation 109 (15.1) 375 (52.0) 113 (15.7) 116 (16.1) 8 (1.1) 0.0001 ems-non-als 15 (11.0) 68 (50.0) 27 (19.9) 18 (13.2) 8 (5.9) 0.0001 ems-als 20 (10.8) 96 (51.6) 32 (17.2) 30 (16.1) 8 (4.3) transportation distance (kilometers) mean ± sd 9.79 ± 7.17 24.75± 28.64 32.39 ± 30.56 38.55 ± 37.07 35.47±4.86 0.0001 ed-los (hours) ≤ 2 23 (15.2) 74 (49.0) 15 (9.9) 33 (21.9) 6 (4.0) 0.0001 2-4 45 (12.9) 106 (30.3) 52 (14.9) 119 (34.0) 28 (8.0) 0.001 ≥ 4 31 (2.7) 374 (33.1) 197 (17.4) 417 (36.9) 110 (9.7) data are presented as mean ± standard deviation (sd) or frequency (%). esi: emergency severity index; rems: rapid emergency medicine score. ed-los: emergency department length of stay; copd: chronic obstructive pulmonary disease; ems-als: emergency medical service ambulance with advanced life support. based on emergency severity index (version 4) (13). patients who were directly admitted to inpatient wards (not through this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. katsomboon et al. 4 table 3: ordinal logistic regression analysis of 24-hour clinical outcome-associated factors in patients admitted to emergency department (n=1,630) factor estimate wald or 95% ci p lower upper age -0.035 0.004 0.965 0.958 0.973 <.001* underlying disease coronary artery disease 0.342 5.347 1.408 1.054 1.882 .021* none ref severity of illness rems at triage .093 15.072 1.097 1.047 1.150 <.001* rems at discharge .248 77.081 1.281 1.212 1.354 <.001* transportation distance 0.007 8.224 1.007 1.002 1.011 0.004* mode of transportation inter-hospital transfer 0.577 7.148 1.781 1.167 2.718 0.008* self-transportation -0.251 2.356 0.778 0.565 1.072 0.125 ems-non-als 0.085 0.147 1.089 0.705 1.681 0.701 ems-als ref length of stay in emergency department ≥ 4 hours -1.573 75.669 0.207 0.146 0.296 <.001* 2-4 hours -.521 18.515 0.594 0.468 0.753 <.001* ≤ 2 hours ref ci: confidence interval; or: odds ratio; rems: rapid emergency medicine score; ems-als: emergency medical service ambulance with advanced life support. ed), discharged home directly from ed, or transferred to another hospital were excluded. patients who had been treated as inpatients in community hospitals and referred to eds at provincial hospitals were also excluded. 2.3. data gathering after the patients were stabilized in the ed, research assistants approached them and explained the research objectives and procedures to them. patients received routine standard care at ed and inpatient wards. clinical data were documented by nurses or attending physicians in paper and electronic formats. research assistants then collected these data after 24 hours of hospitalization. the research assistants underwent a 2-hour intensive training on data collection for this project. patients’ sex and age, underlying disease, severity of illness, transportation distance, mode of transportation, and length of stay in ed were evaluated. severity of illness was assessed using rapid emergency medicine score (rems) (14). rems is comprised of six physiological parameters of age, respiratory rate, oxygen saturation, body temperature, systolic blood pressure, pulse rate, and level of consciousness. the rems score can be used in both trauma and non-trauma patients. higher rems is associated with an or of 1.51 for in-hospital mortality (95% ci 1.45-1.58) (14). mode of transportation referred to how the patient was transported for definitive treatment in the ed of the provincial hospital. in this study, modes of transportation included selftransportation (i.e., a patient was transported by self, family, or bystander), ems ambulance with advanced life support (ems-als), ems ambulance with non-advanced life support (ems-non-als), and inter-hospital transportation. in the former three modes, a patient was directly transported to the ed of a provincial hospital. in the latter mode, a patient first presented to and was treated at a nearby community hospital and thereafter transported to the ed of a provincial hospital. transportation distance, in kilometer, was determined by the distance between the location where the emergency took place and the provincial hospital. ed-los, in minutes, was defined as the interval between the patient’s triage to ed discharge. 2.4. outcome measurement the clinical outcome was measured using pre-arrest sign score, which was assessed and documented 24 hours after hospitalization by a nurse in intensive care unit (icu) or general ward where the patient was treated following ed. the pre-arrest sign, a term widely used in thailand, is in fact a tool originally known as an activation criteria for a medical emergency team (15). the activation criteria for a medical emergency team takes into account presenting symptoms, physiological conditions, and laboratory results, which indicate the risk of cardiopulmonary arrest, and hence pre-arrest signs as referred to by thai clinicians. the score ranges from 0-11. high scores indicate high risk for cardiopulmonary arthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e30 rest. in this study, the scores were classified into 5 levels: 8-11 points: severe critical condition/very high risk of cardiac arrest 5-7 points: critical condition and high risk of cardiac arrest 4 points: moderate risk of cardiac arrest 2-3 points: low risk of cardiac arrest 0-1 point: no sign of cardiac arrest 2.5. statistical analysis the formula for survival studies (16) was used for sample size calculation. in the previous study, 17.7% of patients who were treated in ed were placed in intensive care units (17) and were, therefore, considered critically ill. for multistratified random sampling, the sample size of 1,630 was needed. to ensure that samples are adequate, 30 more patients were added to the calculated sample size, resulting in the sample size of 1,660. the statistical package for the social sciences for the ms windows program (spss/fw ) (version 21.0) was used for data analysis. descriptive statistics, univariate regression analysis, and ordinal multivariate logistic regression analysis with a backward technique were performed. a p value cut-off of <0.05 and confidence interval of 95% were used. 3. results 3.1. baseline characteristics of patients a total of 1,630 patients were finally enrolled in the study (figure 1). the majority were male (57.2%). the mean age was 59.95 + 17.3 (18-98) years. the majority suffered from critical illnesses involving respiratory system (31.2%) and were triaged as esi level 2 (66.5%). the most common modes of transportation were self-transportation (44.3%) and inter-hospital transportation (35.9%). only 11.6% and 8.2% used ems-als and ems-non-als, respectively. mean rems at triage was 6.9 ±3.5 (range 0 -24) points, while mean rems at discharge from ed was 5.7 ± 3.24 (range 0 -24) points (table 1). 3.2. clinical outcome at 24 hours based on prearrest sign based on pre-arrest sign scores, almost half (47.2 %) of the patients had a low level of critical condition after 24 hours of hospitalization. 21.0% and 19.8% had a high and moderate level of critical conditions, respectively. 3.1% were classified as severe (table1). 3.3. associated factors of 24-hour clinical outcome univariate analysis revealed that age, having underlying disease, severity of illness, mode of transportation, transportation distance, and length of stay in ed were associated with pre-arrest sign 24 hours after hospitalization (table 2). subsequent ordinal logistic regression revealed that increasing age decreased a risk of developing pre-arrest sign or clinical deterioration 24 hours after hospitalization (or: 0.965; 95% ci: 0.958-0.973). patients who had coronary artery disease (cad) were 1.41 times more likely to experience poor outcome (or: 1.408; 95% ci: 1.0541.882). every 1-point increase in rems score at triage increased the risk of clinical deterioration by 1.09 times (or: 1.097; 95% ci: 1.047-1.150). a 1-point increase in rems scores at ed discharge, increased the risk of clinical deterioration by 1.28 times (or: 1.281; 95% ci: 1.212 – 1.354). an increase of 1 kilometer of transportation distance increased the risk of poor outcome by 1.01 times (or: 1.007; 95% ci: 1.002-1.011). self-transportation and ems-non-als transportation produced similar clinical outcomes when compared to ems-als transportation. patients transported by inter-hospital transfer were 1.78 times more likely to experience deteriorations compared to emsals (or: 1.781; 95% ci: 1.1672.718). patients who stayed in ed between 2-4 hours or over 4 hours were less likely to experience clinical deteriorations compared to those who stayed less than 2 hours [(or: 0.594; 95% ci: 0.468 0.753) and (or: 0.207; 95% ci: 0.146-0.296), respectively]. 4. discussion having cad, severity of illness, increased transport distance, and ed-los of less than 2 hours were found to negatively influence 24-hour clinical outcome of emergency patients. increasing age was found to positively influence the outcome. modes of transportation (i.e., self-transportation, ems-als, and ems-non-als) did not influence the outcome. we had hypothesized that increasing age of the patient was a risk factor for poor outcome. to our surprise, our result was the opposite. in this study, the older the patients were, the less likely they were at risk of developing pre-arrest sign. the only possible explanation concerns past experience of older persons in relation to how they recognize and respond to warning signs of their underlying illnesses. emergency medical events experienced by older persons in the past may help them and their family to recognize early changes in their signs and symptoms. in the present study, having cad was a risk factor for poor outcome. cad has been well-documented as a risk factor of cardiac arrest (18, 19). patients with existing cad are more likely to develop cardiopulmonary arrest than those with other pre-existing conditions (19). this finding has several implications for pre-hospital and in-hospital service management. pre-hospital assessment of emergency patient should include a question about pre-existing cad. optimal pre-hospital service arrangements for cad patients, including equipment and staff with competencies in cad managethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. katsomboon et al. 6 ment, should be considered. severity of illness on ed triage and ed discharge, as determined using rems, was another predictor of poor clinical outcome. a recent study by ala et al. (2020) (20) suggested that rems correlated with mortality at 48 hours and 30 days. in line with emergency service, our finding suggested that rems may have potential use in pre-hospital, ed, and handover of clinical information for continuous care following ed discharge to icu or wards. mode of transportation (self-transportation, ems-non-als, and ems-als) did not make a difference in pre-arrest sign at 24 hours. in thailand, families and bystanders are familiar with the latter two choices of emergency transportation. when encountering an emergency event, they are required to call the emergency dispatch center or 1669. however, a decision to call or not to call 1669 is influenced by a number of factors such as perceived transport delay and severity of the patients. the patients using self-transportation arrived at the hospital in a shorter time and had a lower level of severity compared to those using ems transportation and pre-arrest sign was, therefore, not different between selftransportation, ems-non-als, and ems-als in our study. our findings are similar to those of a previous study by seamon, et al. (21). in this study, inter-hospital transportation mode was likely to experience poorer clinical outcome compared to those transported by ems-als. we understand that the increased risk of poor outcome may be related to transportation distance and time. previous studies reported an increased risk of clinical deteriorations during inter-hospital transfer of critically ill and emergency patients (22). transportation distance has shown to increase pre-arrest sign. in long-distance transportation, patients are more likely to experience delay in access to definitive care. these contribute to the increased risk of poor outcome among emergency patients requesting service from a long distance. the previous national quality standard indicator in thailand required that ed-los is maintained less than 2 hours (23). previous studies on the effects of ed-los on inpatient mortality reported conflicting results. indian and american studies (9, 24) concluded that ed-los had no effect on inpatient mortality rates, whereas an indian study (9) revealed the effect of longer ed-los on higher rate of inpatient death. our findings, however, suggested that shorter stay (less than 2 hours) was associated with higher risk for developing prearrest signs. this can be explained by the fact that the majority (85.5%) of the patients were admitted to general wards compared to only 14.5% admitted to icu and semi-intensive care unit. continuous management of emergency and critically ill patients at general wards can be very challenging. these general units are often overworked and understaffed. our study points out that more time at ed may be beneficial for the patients as it allows clinical conditions to be improved and sustained in the ed and makes it less complex to be managed in general wards. the ministry of public health has very recently increased the ed target length of stay to 2-4 hours (25). the results of this study highlight two important processes in emergency medical services in thailand: safe and early arrival of emergency patients at ed for definitive care and adequate management and stabilization of emergency patients in ed before inpatient admission. 5. conclusion having cad, severity of illness, increased transport distance, and shorter ed-los of less than 2 hours were found to negatively influence 24-hour clinical outcome of emergency patients. increasing age was found to positively influence the outcome. modes of transportation (i.e., self-transportation, ems-als, and ems-non-als) did not influence the outcome. 6. declarations 6.1. acknowledgments we thank all the participants in this study as well as staff and health professionals for their facilitation during data collection. 6.2. authors’ contributions k.k. and s.s.; contributed to conception, study design. k.k.; contributed to data gathering and evaluation. k.k., s.s and v.c.; contributed to statistical analysis, and interpretation of data. k.k.; drafted the manuscript, which was revised by k.k. and s.s. all authors read and approved the final manuscript. 6.3. funding and supports research assistantships, mahidol university 6.4. conflict of interest the authors declared that they have no potential conflicts of interests with respect to the research, authorship, and/or publication of this article. references 1. stefanovski ph, vladimir radkov r, lyubomir ilkov t, pencho tonchev t, yoana mladenova t, vihar manchev k, et al. analysis of mortality in the emergency department at a university hospital in pleven. j int med res. 2017;45(5):1553-61. 2. heymann ep, wicky a, carron p-n, exadaktylos ak. death in the emergency department: a retrospective this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e30 analysis of mortality in a swiss university hospital. emerg med int. 2019;2019:5263521. 3. christensen 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adverse events and outcomes for adult critically ill patients transferred by paramedics to a tertiary care medical facility. j health spec. 2017;5(4):206. 23. health moph. 2020 [cited 2020 november 22nd]. available from: http://healthkpi.moph.go.th/kpi2/kpi/index2/?kpi_year =2561 24. stey am, kanzaria hk, dudley ra, bilimoria ky, knudson mm, callcut ra. emergency department length of stay and mortality in critically injured patients. j intensive care med. 2022;37(2):278-87. 25. health moph. 2020 [cited 2022 january 20th]. available from: https://phdb.moph.go.th/main/upload/web_news_files/ 95o0rrqbu6scks4go4.pdf. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e7 or i g i n a l re s e a rc h association of ct scan parameters with the risk of renal angiomyolipoma rupture; a brief report razieh heidari1, mostafa ghadamzadeh2, mansour bahardoust3, forugh khezrian1, afrooz moradkhani1 parmida ghadimi4, seyed morteza bagheri2∗ 1. department of radiology, iran university of medical sciences, tehran, iran. 2. department of radiology, hasheminejad kidney center (hkc), iran university of medical sciences, tehran, iran. 3. department of epidemiology, school of public health, shahid beheshti university of medical sciences, tehran, iran. 4. factually of medicine, iran university of medical sciences, tehran, iran. received: november 2021; accepted: november 2021; published online: 1 january 2022 abstract: introduction: rupture of renal angiomyolipoma (aml) is an emergency and life-threatening complication. this study aimed to evaluate the association of computed tomography (ct) scan parameters with the risk of rupture in renal amls. methods: in this retrospective cross-sectional study, patients who were referred to a referral university hospital with diagnosis of aml, between 2007 and 2019, were included. patients were divided into ruptured and non-ruptured cases based on surgery and ct scan findings and the baseline characteristics as well as ct scan parameters were compared between the two groups. results: 20 aml patients with the mean age of 39.6 ± 12.5 years were included (75% female). the lesion was ruptured in 8 (40%) patients. the mean size of the lesion was 97.0 ± 15.9 mm in the ruptured and 72.0 ± 29.4 in the non-ruptured aml (p = 0.045). the mean fat density based on non-contrast enhanced ct (ncct) scan (-56.1 ± 16.3 vs -74.9±24.1; p = 0.018) and contrast enhanced ct (cect) scan (-20.8 ± 16.9 vs -50.5 ± 31.7; p = 0.016) was significantly higher in the ruptured cases. total tumor density based on ncct scan was significantly greater in the ruptured amls (19.6 ± 25.9 vs -22.7±41.6, p=0.033). conclusion: it seems that some ct scan parameters such as mean fat density and total tumor density could be used for differentiation between ruptured and non-ruptured amls. keywords: angiomyolipoma; kidney; tomography, x-ray computed; neoplasms; rupture; emergencies cite this article as: heidari r, ghadamzadeh m, bahardoust m, khezrian f, moradkhani a, ghadimi p, bagheri s m. nifekalant versus amiodarone for out-of-hospital cardiac arrest with refractory shockable rhythms; a post hoc analysis. arch acad emerg med. 2022; 10(1): e7. https://doi.org/10.22037/aaem.v10i1.1472. 1. introduction angiomyolipoma (aml) is the most common benign tumor of the kidney, composed of blood vessels, muscle, and fat, with a prevalence of 0.2 0.6% and a strong female predilection (1). they are asymptomatic in most patients, and the diagnosis is usually made incidentally. the lesion remains stable in many patients and is managed with periodic evaluations and close monitoring of the lesion’s behavior. however, it could become complicated with tumor rupture and retroperitoneal hemorrhage, which are considered ∗corresponding author: seyed morteza bagheri; radiology department, valinezhad street, tehran, iran. telephone: +98-9121150807, fax: +98-2188644441, email: bagheri.m@iums.ac.ir, orcid: https://orcid.org/0000-00015669-1267. emergency and life-threatening consequences (2). to avoid the life-threatening consequences of aml hemorrhage, the risk of tumor rupture is determined based on the tumor size, and surgical intervention is generally performed for tumors sized 4 to 8cm (3, 4). however, a smaller size does not always preclude the risk of tumor rupture, and aml hemorrhage has also been reported in tumors smaller than 4cm (5). in addition, several other risk factors have also been reported to be associated with aml rupture in recent studies (5). many precipitating factors trigger aml rupture, pregnancy plays an important role in tumor growth and rupture, genetic alteration is also the innate reason for tumor rupture (5). therefore, further characterization of patients at high risk for rupture is necessary to prevent under-treatment of the patients. imaging, particularly computed tomography (ct) scan, plays a critical role in diagnosing and managing renal amls. in addition to mass size, the identification of adithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. heidari et al. 2 pose tissue is the cornerstone of the diagnosis of the classic aml (2). limited studies have investigated the risk factors associated with rupture and their prognosis (6). this study aimed to evaluate the association of computed tomography (ct) scan parameters with the risk of rupture in renal amls. 2. methods 2.1. study design and setting in this retrospective cross-sectional study, patients who were referred to a referral university hospital with an imaging diagnosis of aml (lipomatous components in the tumor mass observed on non-enhanced ct scan), between 2007 and 2019, were included. patients were divided into ruptured and nonruptured cases based on surgery report in patients with available data and ct findings including mass irregularity, heterogenicity, and free fluid in abdominopelvic cavity. the baseline characteristics as well as ct scan parameters were compared between the two groups. this study was approved in ethics committee of iran university of medical sciences (ethical code: ir.iums.rec. 1399.636), tehran, iran. the research team of this study adhered to the ethical principles of the helsinki convention regarding clinical studies. 2.2. participants sampling was done consecutively, choosing the cases available during the study period. patients with a prior treatment history and inadequate imaging records were excluded from the study. 2.3. data gathering the demographic characteristics of the patients, including age and gender were extracted from the patients’ medical profiles. in addition, patients’ ct scan records were reviewed for the laterality of the lesion(s), number of the lesions, tumor size, vessel diameter, fat percentage, and total and subtotal fat density based on non-contrast enhanced ct (ncct) scan and contrast enhanced ct (cect) scan, as well as total contrast enhancement. the largest tumor diameter was regarded as the tumor size. the fat percentage was reported based on the visual estimate of the fat content detectable by ct scan (7). accordingly, the amls were categorized into three subsets including fat-low (≤25%), fat-moderate (25-75%), and fat-rich (≥75) lesions. two expert radiologists separately estimated the fat content. in case of any disagreement between the two observers, a third radiologist was consulted to reach a consensus. 2.4. statistical analysis spss for windows, version 16 (spss inc., chicago, ill., usa), was used for the statistical analysis of data. descriptive statistics were provided as mean ± standard deviation or number and percentage. a comparison of the mean between the two groups was made using a mann–whitney u test. categorical variables were compared using the chi-square or fisher’s exact test. a p-value <0.05 was considered significant. 3. results 3.1. baseline characteristics of studied cases finally, 20 aml patients with the mean age of 39.6±12.5 years were studied, in 8 (40%) of whom the lesion was ruptured (75% female). table 1 compares the baseline characteristics of cases between ruptured and non-ruptured cases. the two groups were similar regarding the mean age (p = 0.9), gender (p = 0.7), number of lesions (p = 0.15), and laterality of lesion (p = 0.26). 3.2. ct scan characteristics in the ruptured group, the lesion was fat-low in 2 (25%) patients and fat-moderate in 6 (75%) patients. in the nonruptured group, the lesion was fat-low in 3 (25%) patients, fat-moderate in 6 (50%) patients, and fat-rich in 3 (25%) patients. the fat percentage was not significantly different between the two groups (p = 0.29). table 2 compares the ct scan characteristics between two groups. fat density based on ncct (p = 0.018), fat density based on cect (p = 0.016), and total tumor density based on ncct (p = 0.033) were significantly higher in ruptured cases. 4. discussion in this study, we evaluated the role of ct scan parameters in predicting the rupture of renal aml. ct scan parameters, particularly fat density based on ncct and cect and total tumor density based on ncct, were significantly higher in patients with a ruptured aml. tumor size was significantly larger in the ruptured amls. no significant association was found between other ct parameters and the risk of aml rupture. no significant association was found between the demographic characteristics of the patients and the risk of aml rupture, as well. it is widely accepted that an aml size of >4cm is associated with a higher risk of tumor rupture. in the present study, the size of aml was greater in the ruptured amls. however, the size of the lesion was also more than 4cm in the majority of non-ruptured aml. these observations suggest a predictive role for other aml rupture parameters besides the tumor size. wang et al. reviewed the recent radiological and clinical findings associated with aml rupture. according to their results, in addition to the lesion size, genetic abnormality, aneurysm formation, and pregnancy were also associated with the risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e7 table 1: comparison of baseline characteristics between the ruptured and non-ruptured renal angiomyolipoma cases variable ruptured (n=8) non-ruptured (n=12) p-value age(year) 40.2±10.3 39.3±14 0.9 gender male 2 (25.0) 3 (25.0) 0.7 female 6 (75.0) 9 (75.0) number of lesions 1 4 (50.0) 6 (50.0) 2 2 (25.0) 0 (0.0) 0.15 >2 2 (25.0) 6 (50.0) laterality left 2 (25.0) 6 (50.0) 0.26 right 6 (75.0) 6 (50.0) pseudo-aneurysm no 7 (87.5) 11 (91.7) 0.65 yes 1 (12.5) 1 (8.3) data are presented as mean ± standard deviation or number (%). table 2: comparison of computed tomography scan characteristics between the ruptured and non-ruptured renal angiomyolipoma (amls) variables ruptured (n=8) non-ruptured (n=12) p-value fat content low 2 (25.0) 3 (25.0) moderate 6 (75.0) 6 (50.0) 0.29 rich 0 (0.0) 3 (25.0) tumor size (mm*) 97±15.9 72±29.4 0.045 vessel diameter (mm) 4.2±2.3 3.8± 2 0.65 total density after contrast (hu**) 43.8±42.4 21.8±72.9 0.27 highest density after contrast (hu) 85.6±36.5 78±41.5 0.49 soft-tissue density after contrast (hu) 74.4±32.9 75.5±53.7 0.81 fat density before contrast (g/cm3 ***) -56.1±16.3 -74.9±24.1 0.018 fat density after contrast (hu) -20.8±16.9 -50.5±31.7 0.016 total density without contrast (hu) 19.6±25.9 -22.7±41.6 0.033 highest density without contrast (hu) 44.5±28.6 38.7±50 0.37 total enhancement (hu) 24.1±20.1 32.6±16.3 0.13 fat enhancement (hu) 35.5±11.8 24.4±10.1 0.068 data are presented as mean ± standard deviation or number (%). *mm: millimeter; **:hu: hounsfield unit; ***: g/cm3 : gram per cubic centimeter. of aml rupture. they concluded that any decision for surgical intervention in aml should be based on the cumulative effects of the introduced risk factors and not just on the tumor size (5). yamakado et al. evaluated the association of tumor size and aneurysm formation with spontaneous rupture in 29 kidneys with aml. tumor and aneurysm sizes were compared between the ruptured and non-ruptured aml. the lesion was hemorrhagic in 8 patients. according to their results, tumor size was >4 cm and aneurysm size was ≥5 mm in all hemorrhagic lesions. multiple regression analysis revealed that aneurysm size was the most important predictive factor for aml rupture. however, the size of an aneurysm seems to be corresponding to the tumor size, and larger aneurysms often appear in larger tumors. therefore, the size of an aneurysm could be a reflection of tumor size (3). gandhi et al. used 64 slices of multidetector computed tomography and angiography to investigate the association of tumor size and aneurysm formation with spontaneous rupture of renal aml in 27 patients (34 kidneys, 6 ruptures, and 28 non-ruptured amls) (8). in contrast to the study of yamakado et al. (3), tumor and aneurysm size could not predict the spontaneous rupture of the aml in the study of gandhi et al. these results indicate the need for further studies evaluating factors affecting the rupture of aml. several other studies have also attempted to establish novel risk factors for aml rupture (9, 10). however, the attempt to find more reliable markers of aml rupture continues. ct this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. heidari et al. 4 scan is an imperative imaging modality in the diagnosis of aml (11). some authors have used ct finding to estimate the risk of rupture in aml (12, 13). recent evidence suggests an association between fat content and rupture of aml (14). accordingly, we hypothesized that quantifying the fat content of the aml based on ct images could be used as a predictive factor of lesion rupture. according to our results, fat density based on ncct and cect and total tumor density based on ncct were significantly higher in the ruptured amls. therefore, they could be promising parameters for predicting aml rupture and performing prophylactic surgery/intervention. 5. limitations despite the promising findings of this study, it should be noted that the present results might be flawed for several reasons and further studies are required to confirm the results obtained here. firstly, it was a retrospective study with potential information bias. secondly, the small number of patients might have affected the power of the statistical analysis. finally, the number of patients was not large enough to perform multivariate analysis. 6. conclusion ct scan parameters, particularly fat density based on ncct and cect and total tumor density based on ncct, could be used for predicting the risk of rupture in renal aml and performing prophylactic surgery/intervention to prevent lifethreatening consequences of the aml hemorrhage. despite the promising role of ct scan parameter in this differentiation, the results need to be re-confirmed in prospective largescale studies. 7. declarations 7.1. acknowledgments hereby, the authors would like to express gratitude to the guidance and advice from the “clinical research development unit of hasheminejad kidney center (hkc), tehran, iran”. 7.2. author contribution all the authors of this study met the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding no funding was received for this study. 7.4. conflict of interest none declared. references 1. fittschen a, wendlik i, oeztuerk s, kratzer w, akinli as, haenle mm, et al. prevalence of sporadic renal angiomyolipoma: a retrospective analysis of 61,389 inand outpatients. abdominal imaging. 2014;39(5):1009-13. 2. flum as, hamoui n, said ma, yang xj, casalino dd, mcguire bb, et al. update on the diagnosis and management of renal angiomyolipoma. the journal of urology. 2016;195(4 pt 1):834-46. 3. yamakado k, tanaka n, nakagawa t, kobayashi s, yanagawa m, takeda k. renal angiomyolipoma: relationships between tumor size, aneurysm formation, and rupture. radiology. 2002;225(1):78-82. 4. dickinson m, ruckle h, beaghler m, hadley hr. renal angiomyolipoma: optimal treatment based on size and symptoms. clinical nephrology. 1998;49(5):281-6. 5. wang c, li x, peng l, gou x, fan j. an update on recent developments in rupture of renal angiomyolipoma. medicine (baltimore). 2018;97(16):e0497. 6. fernández-pello s, hora m, kuusk t, tahbaz r, dabestani s, abu-ghanem y, et al. management of sporadic renal angiomyolipomas: a systematic review of available evidence to guide recommendations from the european association of urology renal cell carcinoma guidelines panel. european urology oncology. 2020;3(1):57-72. 7. milner j, mcneil b, alioto j, proud k, rubinas t, picken m, et al. fat poor renal angiomyolipoma: patient, computerized tomography and histological findings. the journal of urology. 2006;176(3):905-9. 8. gandhi sp, pal bc, patel kn, sutariya h, trivedi hl. role of 64 slice multidetector computed tomography and angiography to establish relationship between tumor size, aneurysm formation and spontaneous rupture of renal angiomyolipomas: single center experience. urology annals. 2016;8(2):173. 9. santos mmld, proença sms, reis minpda, viana rmal, martins lmb, colaço jmdr, et al. spontaneous rupture of renal angiomyolipoma during pregnancy. revista brasileira de ginecologia e obstetrícia. 2014;36:377-80. 10. zapardiel i, delafuente-valero j, bajo-arenas jm. renal angiomyolipoma during pregnancy: review of the literature. gynecologic and obstetric investigation. 2011;72(4):217-9. 11. bosniak ma, megibow aj, hulnick dh, horii s, raghavendra bn. ct diagnosis of renal angiomyolipoma: the importance of detecting small amounts of fat. ajr american journal of roentgenology. 1988;151(3):497-501. 12. bagheri sm, khajehasani f, fatemi i, ayoubpour mr. tumoral vascular pattern in renal cell carcinoma and fat-poor renal angiomyolipoma as a novel helpful differentiating factor on contrast-enhanced ct scan. tuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e7 mour biology : the journal of the international society for oncodevelopmental biology and medicine. 2017;39(10):1010428317733144. 13. lu cy, min pq, wu b. ct evaluation of spontaneously ruptured renal angiomyolipomas with massive hemorrhage spreading into multi-retroperitoneal fascia and fascial spaces. acta radiologica short reports. 2012;1(4):16. 14. koo kc, kim wt, ham ws, lee js, ju hj, choi yd. trends of presentation and clinical outcome of treated renal angiomyolipoma. yonsei medical journal. 2010;51(5):72834. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e43 rev i ew art i c l e adherence to referral criteria for burn patients; a systematic review ali bazzi1,2, mohammad javad ghazanfari2,3, masoumeh norouzi1∗, mohammadreza mobayen2, fateme jafaraghaee4, amir emami zeydi5, joseph osuji6, samad karkhah1,2,7 † 1. department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 2. burn and regenerative medicine research center, guilan university of medical sciences, rasht, iran. 3. department of medical-surgical nursing, school of nursing and midwifery, kashan university of medical sciences, kashan, iran. 4. school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 5. department of medical-surgical nursing, nasibeh school of nursing and midwifery, mazandaran university of medical sciences, sari, iran. 6. school of nursing and midwifery, faculty of health, community, and education, mount royal university, calgary, ab, canada. 7. quchan school of nursing, mashhad university of medical sciences, mashhad, iran. received: march 2022; accepted: april 2022; published online: 2 june 2022 abstract: introduction: burn injuries are under-appreciated trauma, associated with substantial morbidity and mortality. it is necessary to refer patients in need of specialized care to more specialized centers for treatment and rehabilitation of burn injuries. this systematic review aimed to assess the adherence to referral criteria for burn patients. methods: an extensive search was conducted on scopus, pubmed, and web of science online databases using the relevant keywords from the earliest to october 7, 2021. the quality of the included studies was assessed using the appraisal tool for cross-sectional studies (axis tool). results: among a total of 7,455 burn patients included in the nine studies, 60.95% were male. the most frequently burned areas were the hands (n=3) and the face (n=2). the most and least common burn mechanisms were scalds (62.76%) and electrical or chemical (2.88%), respectively. 51.88% of burn patients had met ≥ 1 referral criteria. the overall adherence to the referral criteria for burn patients was 58.28% (17.37 to 93.39%). the highest and lowest adherence rates were related to western cape provincial (wcp) (26.70%) and national burn care review (nbcr) (4.97%) criteria, respectively. conclusion: the overall adherence to the referral criteria for burn patients was relatively desirable. therefore, well-designed future studies are suggested in order to uncover approaches to improve adherence to referral criteria for burn patients. keywords: burns; guideline adherence; referral and consultation; systematic review cite this article as: bazzi a, ghazanfari mj, norouzi m, mobayen m, jafaraghaee f, emami zeydi a, osuji j, karkhah s. adherence to referral criteria for burn patients; a systematic review. arch acad emerg med. 2022; 10(1): e43. https://doi.org/10.22037/aaem.v10i1.1534. 1. introduction burn injuries are under-appreciated trauma associated with substantial morbidity and mortality (1-9). based on the re∗corresponding author: masoumeh norouzi; nursing and midwifery school of shahid dr. beheshti, hamidyan shahrak, shahid dr. beheshti ave., rasht, iran. postal code: 41469-39841. fax: +98-13-33550097, tel: +98-13-33552088, email: contact1995@yahoo.com, orcid: http://orcid.org/0000-0002-2892944x. † corresponding author: samad karkhah; nursing and midwifery school of shahid dr. beheshti, hamidyan shahrak, shahid dr. beheshti ave., rasht, iran. postal code: 41469-39841. fax: +98-13-33550097, tel: +98-9032598167; , email: sami.karkhah@yahoo.com, orcid: http://orcid.org/0000-0001-9193-9176. port by world health organization, 11 million burns occur annually worldwide, 180,000 are fatal (10). therefore, it is necessary to refer patients in need of specialized care to more specialized centers for treatment and rehabilitation of burn injuries (11). meanwhile, referral criteria for transferring burn patients to burn specialty centers have been proposed by various burn associations in the usa, the united kingdom, and australia and new zealand (11). however, despite using referral criteria for burn patients for more than two decades, there is still limited information on adherence to these criteria. in the netherlands, adherence to the emergency management of severe burns (emsb) criteria in patients primarily presentthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bazzi et al. 2 ing to a non-burn center was 70.03% (11) two studies in the usa showed that adherence to the american burn association (aba) and emsb criteria in patients primarily presenting to a non-burn center was 48.00% and 54%, respectively (12, 13). however, a study in the united kingdom found that adherence to the british burns association (bba) criteria in burn patients was 25.31% (14). the need to adhere to these criteria worldwide and the possible improved outcomes for burn patients cannot be overemphasized, hence the need to conduct this systematic review. limited and contradictory studies have been published on adherence to referral criteria for burn patients. this systematic review aimed to assess the adherence to referral criteria for burn patients. 2. methods this systematic review was based on the preferred reporting items for systematic reviews and meta-analyzes (prisma) guidelines (15). 2.1. search strategy an extensive search was conducted on scopus, pubmed, and web of science online databases using keywords such as "burns", "guideline adherence", “patients”, and "referral criteria" from the earliest to october 7, 2021. for example, the search strategy in pubmed/medline database was ((“guideline adherence”) or (“policy compliance”) or (“protocol compliance”) or (“institutional adherence”) or (“adherence, institutional”)) and ((“referral criteria”) or (“hospital referral”) or (“guidelines”) or (“standards”) or (“reference standards”) or (“criteria”) or (“referral”) or (“consultation”) or (“consultation and referral”)) and ((“burns”) or (“patients”) or (“clients”)). keywords were extracted from the medical subject headings and combined using boolean operators (and/or). two researchers performed the search steps, independently. in the present systematic review, the gray literature such as conference presentations, expert opinion, dissertations, research and committee reports, and ongoing research were not seriously searched because they did not fully depict the results, and the results may completely change when they are not published. gray literature is defined as papers that are produced in print and electronic formats but are not controlled by commercial publishers (16). 2.2. inclusion and exclusion criteria in this review, studies published in english, focusing on adherence to referral criteria for burn patients were included (table 1). the corresponding authors were contacted in cases of lack of access to articles or where relevant data was missing. 2.3. study selection endnote x8 software was used to manage the data. duplicate articles were removed, first electronically and then manually. title, abstract, and full text of articles were assessed based on inclusion/exclusion criteria. the reference list of eligible studies was reviewed to prevent missing relevant information. in case of disagreement between researchers, the articles were evaluated by a third researcher. 2.4. data extraction and quality assessment assessment of the quality of included studies was performed by two researchers. the researchers extracted information from the included studies. the information included the name of the first author, year of publication, location, sample size, male/female ratio, age, source of data collection, length of stay, burn mechanism, number of referral criteria met, the most frequently burned area, rate of adherence to referral criteria, the highest and lowest rates of adherence to referral criteria, instrument, and key results. the quality of the included studies was assessed using the appraisal tool for cross-sectional studies (axis tool). this tool evaluates the quality of the included studies using 20 items (17). 3. results 3.1. study selection a total of 822 studies (pubmed=268, web of science=135, and scopus=419) were obtained via an initial database search, and three studies were obtained using the assessment of the reference list of eligible studies. also, 216 and 123 duplicate records were removed electronically and manually, respectively. in the screening stage of the title and abstract of studies, out of 483 studies, 425 articles were removed due to the obvious irrelevance of their topics with this research and 33 studies were excluded due to the type of the studies (animal studies, experimental studies, case reports, editorial letters, conferences papers and dissertations, reviews, etc). after assessment of the full-text of 17 studies, six articles were excluded due to inappropriate study design or outcomes and two articles were excluded due to lack of desired information. finally, nine studies (11-14, 18-22) were included in this systematic review (figure 1). 3.2. study characteristics among the 7,455 burn patients included in the nine studies (11-14, 18-22), 60.95% were male. all studies had a retrospective design. of the studies included, two were in the usa (12, 13), two were in the united kingdom (14, 22), two were in the netherlands (11, 18), one was in canada (20), one was in denmark (21), and one was in south africa (19) (table 2). of the included studies, three studies assessed the aba critethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e43 table 1: eligibility criteria criteria inclusion exclusion participants burn patients patients of all age groups animal studies outcomes rate of adherence to referral criteria for burn patients the highest and lowest rate of adherence to referral criteria study design cross-sectional retrospective case reports experimental studies letters to editors conferences reviews time frame the earliest to october 5, 2021 table 2: basic characteristics of the studies included in this systematic review first author/year study period design source of data collection sample size m/f ratio age* (years) chipp et al., 2008 (14) united kingdom 2004 retrospective west midlands regional burns unit 561 53.00/47.00 n/a carter et al., 2010 (12) usa 2006 to 2007 retrospective north carolina hospital association patient data system 2,036 66.80/33.20 48.05 (sd=17.75) rose et al., 2010 (22) united kingdom 2010 (6-month period) retrospective administrative database 190 55.26/44.74 0 to 15 baartmans et al., 2012 (18) netherlands 2002 to 2004 & 2007 to 2008 retrospective dutch national trauma registry 622 63.51/36.49 > 15 davis et al., 2012 (13) usa 2008 retrospective icd-9 750 n/a 39.00 (sd=23.00) reiband et al., 2014 (21) denmark 2011 (3-months period) retrospective icd-10 97 70.10/29.90 10 months to 71 years boissin et al., 2017 (19) south africa 2011 to 2015 retrospective administrative database 1,165 55.71/44.29 0 to 12 chambers et al., 2021 (20) canada 2018 to 2019 retrospective administrative database 244 62.30/37.70 0.50 to 87 van yperen et al., 2021 (11) netherlands 2014 to 2018 retrospective dutch national trauma registry 1,790 n/a n/a * at time of injury; icd-9: international classification of diseases-9th revision; icd-10: international classification of diseases-10th revision; sd: standard deviation; n/a: not available. ria (12, 13, 20), two studies evaluated the emsb criteria (11, 18), one study assessed the bba criteria (14), one study evaluated the national burn care review (nbcr) criteria (22), one study assessed the national burn center (nbc) criteria (21), and one study evaluated the western cape provincial (wcp) criteria (19) (table 3). 3.3. methodological quality of included study as presented in figure 2, all included studies had justifications for sample size. two studies did not define statistical significance. six studies did not identify limitations. four studies did not report funding sources or conflicts of interest, while four studies did not indicate the ethical approval/informed consent protocols used. 3.4. characteristics of burn patients as shown in table 3, the average length of stay in the hospital for burn patients was seven days. the most frequently burned areas were the hands (n=3) (12, 20, 22) and the face (n=2) (14, 19). the most and least common burn mechanisms were scalds (62.76%) and electrical or chemical (2.88%), respectively (figure 3). 51.88% of burn patients had met ≥ 1 referral criteria (table 3). 3.5. adherence to referral criteria for burn patients the overall adherence to the referral criteria for burn patients was 58.28% (17.37 to 93.39%) (table 4). the highest and lowest rates of adherence were related to wcp (26.70%) and nbcr (4.97%) criteria, respectively (figure 4). 4. discussion this systematic review showed that most frequently burned areas were the hands and the face. the most and least common burn mechanisms were scalds (62.76%) and electrical or chemical (2.88%), respectively. 51.88% of burn patients had met ≥ 1 referral criteria. the overall adherence to the referral criteria for burn patients was 58.28%. the highest and lowest adherence rates were related to wcp (26.70%) and nbcr this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bazzi et al. 4 figure 1: flow diagram of the study selection process. (4.97%) criteria, respectively. as presented in this study, most commonly burned areas were the hands and the face. the greater prevalence of burns on the hands and face can be expected because these body parts are not usually covered. however, differences in burn areas may be due to differences in variables such as culture, customs, habits, geopolitical and climatic location in different societies. for example, in wars such as the iraq and vietnam wars, most of the injured areas were the face and hands due to explosions (23). sunburn on the hands and the face is more common in parts of spain and on cyclists (24). therefore, although most burns occur on the hands and face, further studies are needed to assess the factors associated with it. based on the present study’s findings, the most and least common burn mechanisms were scalds (62.76%) and electrical or chemical (2.88%), respectively. scalds are more common in children (under 14 years old) and are caused by hot liquids. this finding was supported by a study in iraq (25). children are more prone to scalds at home due to their mobility. on the other hand, electrical and chemical burns are less common due to lower exposure of people. however, it is suggested that future studies pay more attention to different age groups in different types of burns. as presented in the present study, 51.88% of burn patients had met ≥ 1 referral criteria. there were differences in the number of referral criteria met in the studies, which can be explained by different referral criteria, family preferences, distance to the burn center, and insurance status (11). the overall adherence to the referral criteria for burn patients was 58.28%. also, the highest and lowest adherence rates were related to wcp (26.70%) and nbcr (4.97%) criteria, respectively. however, there were many differences in studies in terms of adherence to referral criteria. for example, a study in south africa found that adherence to the referral criterion is 93.4% (19). in contrast, another study in the united kingdom found that this adherence was 25.31% (14). this discrepancy may be due to differences in study design, apthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e43 figure 2: assessment of the quality of the included articles. figure 3: burn mechanisms. plicable referral criteria, outcome criteria, and definition of adherence between different studies (11, 14, 19). figure 4: adherence to referral criteria for burn patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bazzi et al. 6 4.1. implications for education, practice, and management adherence to referral criteria for burn patients will improve patient outcomes and ensure that burn patients are managed according to the latest evidence-based approaches. findings of this systematic review indicate that much improvement is needed in educating hospital staff regarding making the necessary and timely referrals of burn patients based on laid down criteria. this calls for strategies that can improve adherence to referral criteria and reduce burn complications. the creation of a comprehensive burn system under the supervision of a burn specialist and the development of standards and evidence-based protocols for burn control, allocation of sufficient resources to burn systems and units, the hiring of adequate human resources, appropriate burn dressing and care, development of appropriate programs for regular visits to patients by burn specialists, and holding appropriate workshops for patients and health care providers can help manage burn patients. 4.2. implications for future research the findings of this systematic review can help improve referral patterns in burn patients admitted to non-burn centers. however, not all referral criteria are appropriate for managing burn patients, and some require serious revision. there is also a need for further research on whether modifying some referral criteria or training physicians in non-burn centers can increase adherence to referral criteria. 4.3. limitations this systematic review had several limitations. although this systematic review was conducted based on the prisma checklist, it was not registered in the international prospective register of systematic reviews (prospero) database, and a public protocol does not exist. despite a comprehensive systematic search in this review, researchers may not have found all studies published in this area. also, language bias cannot be ignored because only english language studies were included in the present study. 5. conclusion although the overall adherence to the referral criteria for burn patients was relatively desirable, there is room for improvement. the highest and lowest adherence rates were related to wcp (26.70%) and nbcr (4.97%) criteria, respectively. therefore, it is suggested to perform well-designed studies that will focus on interventions to improve adherence to referral criteria for burn patients in the future. 6. declarations 6.1. acknowledgments none. 6.2. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. 6.3. authors’ contributions study concept and design by all authors; data acquisition by all authors; data interpretation by all authors; drafting the manuscript by all authors; revision of the manuscript by all authors; the final version of the manuscript is approved by all authors. 6.4. funding and supports none. 6.5. conflict of interest the authors declare no conflict of interest. references 1. miri s, mobayen m, aboutaleb e, ezzati k, feizkhah a, karkhah s. exercise as a rehabilitation intervention for severe burn survivors: benefits & barriers. burns. 2022. 2. mobayen m, ch mh, ghazanfari mj, sadeghi m, mirmasoudi ss, feizkhah a, et al. antibiotics as a two-edged sword: the probability of endotoxemia during burned wound treatment. burns. 2022;48(3):730-1. 3. mobayen m, feizkhah a, ghazanfari mj, toolaroud pb, mobayen m, osuji j, et al. intraoperative threedimensional bioprinting: a transformative technology for burn wound reconstruction. burns. 2022. 4. mobayen m, ghazanfari mj, feizkhah a, mobayen m, zeydi ae, karkhah s. effects of covid-19 pandemic on burns care. burns. 2022. 5. mobayen m, ghazanfari mj, feizkhah a, zeydi ae, karkhah s. machine learning for burns clinical care: opportunities & challenges. burns. 2022;48(3):734-5. 6. mobayen m, zolfagharzadeh h, feizkhah a, ghazanfari mj, toolaroud pb, mobayen m, et al. application of cell appendages for the management of burn wounds. burns. 2022. 7. feizkhah a, mobayen m, ghazanfari mj, toolaroud pb, vajargah pg, mollaei a, et al. machine learning for burned wound management. burns. 2022. 8. jeschke mg, van baar me, choudhry ma, chung kk, gibran ns, logsetty s. burn injury. nat rev dis primers. 2020;6(1):1-25. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 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◦ electrical burns, including lightning injury davis et al., 2012 (13) ◦ chemical burns chambers et al., ◦ inhalation injury 2021 (20) aba ◦ burn injury in patients with preexisting medical disorders that could complicate management, prolong recovery, or affect mortality ◦ any patients with burns and concomitant trauma (such as fractures) in which the burn injury poses a greatest risk of morbidity or mortality. in such cases, if the trauma poses a greater immediate risk, the patient may be initially stabilized in a trauma center before being transferred to a burn unit. physician judgment will be necessary in such situations and should be in line with the regional medical control plan and triage protocols ◦ burned children in hospitals without qualified personnel or equipment for the care of children ◦ burn injury in patients who will require special social, emotional, or long-term rehabilitative intervention age under 5yrs and over 60yrs site involvement face, hands, feet, perineum, flexures particularly neck or axilla, circumferential or full-thickness burns of limbs, torso, or neck inhalation injury excluding pure carbon monoxide poisoning rose et al., mechanism of injury 2010 (22) nbcr ◦ chemical injury (>5% tbsa) ◦ exposure to ionizing radiation ◦ high-pressure steam injury ◦ high-tension electrical injury ◦ hydrofluoric acid injury (>1% tbsa) ◦ suspicion of non-accidental injury (nai) size of skin injury ◦ pediatrics >5% tbsa; adult >10% tbsa this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e43 table 3: referral criteria for the management of burn patients author/year criteria description ◦existing conditions ◦ cardiac limitation or mi in last 5yrs ◦ respiratory limitation of exercise ◦ diabetes ◦ pregnancy ◦ immuno-suppression ◦ hepatic disease associated injuries ◦ crush injuries ◦ fractures ◦ head injuries ◦ penetrating injuries ◦ burns 10% or more tbsa in adults ◦ burns 5% or more tbsa in children (<16 year) baartmans et al., ◦ full thickness burns 5% or more tbsa 2012 (18) ◦ burns of functional areas (face, hands, feet, genitals, perineum, or large joints (i.e., shoulder, elbow, knee, and ankle)) van yperen et al., ◦ circumferential burns of the neck, chest, or extremities 2021 (11) emsb ◦ electrical burns (high voltage) including lightning strikes ◦ chemical burns ◦ burns with suspected associated inhalation injury ◦ any burn patient with associated trauma or (pre-existing) medical condition that may affect treatment and recovery, or could increase mortality ◦ burns at the extremes of age — young children (<1 year) and the elderly (75 years) ◦ non-accidental burns ◦ burns for which the burn mechanism is uncertain in combination with uncertainty about the competence/equipment of the hospital for these types of injuries ◦ burn wound that shows insufficient signs of healing within two weeks ◦ partial thickness burn exceeding 3% ◦ full thickness burn exceeding 1% ◦ suspicion of inhalation injury reiband et al., ◦ high-voltage burns 2014 (21) nbc ◦ circular full-thickness burns ◦ burn to the face ◦ burn over the major joint ◦ burn in the urogenital area ◦ suspicion of non-accidental injury ◦ cases of doubt ◦ age: under 2 years. ◦ severity: partial thickness burns with tbsa >15%, or full thickness burns with tbsa >15%. ◦ anatomical site: face, hands, feet, genitalia, perineum, major joints, or circumferential burns (these burns could also be dealt with at level 1 or 2 but discretion must be used). boissin et al., ◦ inhalation injury: requiring ventilation for more than 48 h. 2017 (19) wcp ◦ mechanism of injury: exposure to ionizing radiation, high pressure steam, high tension electrical injury, hydrofluoric acid injury >1% tbsa, or suspicion of a non-accidental burn injury. ◦ existing co-morbidity: cardiac limitation and/or myocardial infarction within five years, respiratory limitation of exercise, uncontrolled type 1 diabetes, medically or disease-induced immune suppression for any reason, existing psychiatric or suicidal tendencies. ◦ other severe associated injuries: for example, polytrauma or crush syndrome. tbsa: total body surface area; mi: myocardial infarction; bba: british burns association; aba: american burn association; nbcr: national burn care review; emsb: emergency management of severe burns; nbc: national burn center; wcp: western cape provincial. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bazzi et al. 10 table 4: adherence to referral criteria for the management of burn patients (continues) first author/year length of stay in hospital (day) most burned area burn mechanism number of referral criteria met adherence to referral criteria chipp et al., 2008 (14) n/a face ◦ flames (n=253) ≥1 (n=378) 1. the rate of adherence to the bba criteria in burn patients was 25.31% (n=142 out of 561). ◦ scalds (n=112) ◦ inappropriate referral: 156 (27.81%) ◦ contact (n=79) ◦ appropriate referral: 142 (25.31%) ◦ chemical burns (n=34) ◦ over-transferred: 17 (3.03%) ◦ other (n=83) ◦ under-transferred: 246 (43.85%) 2. the highest and lowest adherence to the bba criteria were in tbsa burned and perineum (100%) and axilla (0%) burns, respectively. carter et al., 2010 (12) 9.00 (sd=10.85) wrist & hand n/a ≥1 (n=1,416) 1. the rate of adherence to the aba criteria in patients primarily presented to a non-burn center was 48.00% (n=457 out of 952). 2. the rate of adherence to the aba criteria in a burn center was 79.98% (n=867 out of 1,084). rose et al., 2010 (22) n/a hands ◦ flames (n=9) 1. the rate of adherence to the nbcr criteria in burn patients was 17.37% (n=33 out of 190). ◦ scalds (n=89) ◦0 (n=64) ◦ inappropriate referral: 61 (32.11%) ◦ contact (n=66) ◦ 1 (n=46) ◦ appropriate referral: 33 (17.37%) ◦ electrical or chemical (n=13) ◦ 2 (n=75) ◦ 3 (n=4) ◦ over-transferred: 2 (1.05%) ◦ other (n=13) ◦ 4 (n=1) ◦ under-transferred: 94 (49.47%) baartmans et al., 2012 (18) 6.5 n/a ◦ scalds (n=472) n/a the rate of adherence to the emsb criteria in burn patients was 80.22% (n=499 out of 622). ◦ flames (n=101) ◦ contact (n=10) ◦ other (n=39) davis et al., 2012 (13) 10.50 (sd=18.50) n/a n/a n/a the rate of adherence to the emsb criteria in patients primarily presented to a non-burn center was 46.00% (n=345 out of 750). reiband et al., 2014 (21) n/a partial thickness burns exceeding 3% ◦ flames (n=37) n/a the rate of adherence to the nbc criteria in burn patients was 70.10% (n=68 out of 97). ◦ scalds (n=35) ◦ contact (n=8) ◦ other (n=17) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e43 table 5: adherence to referral criteria for the management of burn patients first author/year length of stay in hospital (day) most burned area burn mechanism number of referral criteria met adherence to referral criteria boissin et al., 2017 (19) 7 face ◦ scalds (n=1,031) ≥1 (n=471) the rate of adherence to the wcp criteria in burn patients was 93.39% (ci: 91.8 to 94.7%). ◦ flames (n=108) ◦ ≥2 (n=606) ◦ electrical or chemical (n=23) ◦ ≥3 or more (n=88) ◦ other (n=3) ◦ chambers et al., 2021 (20) n/a hands ◦ flames (n=68) n/a the rate of adherence to the aba criteria in burn patients was 72.95% (n=178 out of 244). ◦ scalds (n=68) ◦ contact (n=77) ◦ electrical or chemical (n=13) ◦ other (n=18) van yperen et al., 2021 (11) 2 burns of functional areas n/a ◦ ≥1 (n=668) 1. the rate of adherence to the emsb criteria in patients primarily presented to a non-burn center was 70.03% (n=666 out of 951). ◦ ≥2 (n=309) ◦ inappropriate referral: 263 (27.65%) ◦ ≥3 (n=89) ◦ appropriate referral: 403 (42.38%) ◦ ≥4 (n=26) ◦ over-transferred: 20 (2.10%) ◦ ≥5 (n=11) ◦ under-transferred: 265 (27.87%) ◦ ≥6 (n=3) 2. the rate of adherence to the emsb criteria in a burn center was 92.25% (n=1,119 out of 1,213). ◦ ≥7 (n=1) 3. the highest and lowest adherence to the emsb criteria were in children with ≥5% tbsa: total body surface area; bba: british burns association; aba: american burn association; nbcr: national burn care review; emsb: emergency management of severe burns; nbc: national burn center; wcp: western cape provincial; sd: standard deviation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e35 https://doi.org/10.22037/aaem.v9i1.1157 or i g i n a l re s e a rc h prevalence and related factors of post-traumatic stress disorder in emergency medical technicians; a crosssectional study afshin khazaei1, maryam esmaeili2, habib masoumi3, elham navab4∗ 1. intensive care and management nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. critical care department, nursing and midwifery care research center, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 3. disaster and emergency management department, hamadan university of medical sciences, hamadan, iran. 4. critical care and geriatric nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. received: february 2021; accepted: february 2021; published online: 30 april 2021 abstract: introduction: ongoing exposure to a variety of pre-hospital emergencies (pe) has placed emergency medical technicians (emts) at serious psychiatric compromise such as post-traumatic stress disorder (ptsd). the present study aimed to evaluate the prevalence and associated factors of ptsd among emts. methods: this prospective cross-sectional study was conducted on emts in the emergency medical services (ems) in west of iran. a baseline information questionnaire including personal work-related characteristics and the ptsd checklist of dsm-5 (pcl-5) were used for data collection. non-parametric tests and multivariate linear regression were used to evaluate the associated factors of ptsd in these participants. results: among the participants, 22% of technicians had ptsd-diagnostic criteria. the mean total pcl-5 score was 21.60 ± 11.45, while the scores were 38.02 ± 6.08 and 17.47 ± 8.36 in the ptsd-diagnosed and undiagnosed groups, respectively. the most common symptom of the clusters was negative alterations in cognition with a mean score of 7.42 ± 4.63. after adjusting confounders, the number of missions (t= 2.50, p= 0.013), work experience (t= -3.24, p= 0.001) and number of shifts (t: 26.38, p < 0.001) were significantly corelated with pcl-5 score. conclusion: the results indicated that the prevalence of ptsd among emts personnel of hamadan province is high. emts with the age of ≤ 30 years, work experience of ≤ 10 years, married status, informal employment, emergency medical technician’s degree, and more than 8 shifts per month, as well as no previous training history had a higher total pcl-5 score. keywords: emergency medical technicians; emergency medical services; diagnostic and statistical manual of mental disorders; stress disorders, post-traumatic cite this article as: khazaei a, esmaeili m, masoumi h, navab e. prevalence and related factors of post-traumatic stress disorder in emergency medical technicians; a cross-sectional study. arch acad emerg med. 2021; 9(1): e35. 1. introduction emergency medical technicians (emts) experience some cumulative stress, which may be related to traumatic events (1). in addition, frequent and ongoing exposure to potentially traumatic events may place emts at higher risk of serious psychiatric compromise, including post-traumatic stress disorder (ptsd) (2, 3), which is considered as a mental ∗corresponding author: elham navab; school of nursing and midwifery, nosrat st., tohid sq., tehran, iran. 141973317. tel: 00989173110323, email: e_navab100@hotmail.com health disorder leading to social, occupational, and interpersonal disturbance (4). the experience of a traumatic event is not the only effective factor causing ptsd among individuals (5). therefore, identifying risk factors other than exposure to traumatic events, such as personal/work-related characteristics that can predict the development of ptsd, can lead to more effective management and control of prehospital emergency stress in the emts. considering the current overall ptsd prevalence (from 11% to 35%) among emts (6, 7), which is the highest rate among prehospital care providers (8), the need for assessing the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. khazaei and et al. 2 mental health of emts and identifying the staff members at high risk of developing ptsd is crucial. although a large number of studies have examined ptsd in emts using dsm-4 tools, little information is available on assessing ptsd by considering dsm-5 criteria in the ems. therefore, the present study aimed to evaluate the prevalence and associated factors of ptsd among emts. 2. methods 2.1. study design and setting in this cross-sectional study, the data of emts in 20 metropolitan-based, 30 road-based, and one air-based services (serving about two million people) in hamadan province, iran, were collected during july-october 2018. all of the emts in the emergency medical services (ems) in this province were invited to participate in this study. before running the study, the objective of the study was explained to the emts. then, all participants voluntarily signed the consent form and their names and personal information were kept confidential in the questionnaires. the project was approved by the ethics committee in tehran university of medical sciences (no: ir.tums.fnm.rec.1397.042). 2.2. participants operational emts who worked in urban, road, and air emergency bases full-time and gave their oral and written consent were included in the presnet study. however, nonoperational emts, the staff from other medical centers working part-time, and those who experienced non-occupational stressors such as the death of close relatives in the previous eight weeks were excluded. 2.3. data gathering in order to collect the related data, demographic questionnaire (including personal and work-related characteristics) and ptsd checklist for diagnostic and statistical manual of mental disorders-5 (pcl-5), which is regarded as a selfreporting tool that evaluates a variety of purposes such as screening individual for ptsd, were used in this study (10). the pcl5 checklist includes 20 items, divided into four clusters including intrusion (5 items), avoidance (2 items), negative alterations in cognition and mood (7 items) and alterations in arousal and reactivity (7 items). each item is scored on a 5-point likert scale ranging from 0 (not at all) to 4 (extremely) (10). furthermore, the reliability and validity of this checklist have been confirmed in some studies (11-13). although the validity and reliability of the persian version of this instrument were confirmed through using exploratory and confirmatory factor analyses, convergence validity (r=0.68%, p=0.001), and cronbach’s alpha (r=0.79%), as well as retesting (r=0.77%) (14), we reassessed the pcl-5 reliability (r=0.89) for the total score in this study. 2.4. statistical analysis in the study conducted by iranmanesh et al. (9), the reported ptsd rate among emts was 0.22%. the total number of emts was 307, among whom 251 were selected by considering the relative error of 10% and 95% confidence interval. continuous variables were expressed as mean and standard deviation (sd) or median and interquartile ranges (iqrs). categorical variables were reported in frequency and percentages. the total score of symptom severity was obtained by summing the scores related to the 20 items, and ranged from 0 to 80. in addition, a pcl-5 score of less than 33 appears to not require further psychometric work (10, 15, 16). therefore, scores were dichotomized into scores ≥ 33 (meeting the criteria for ptsd) and scores < 33 (not meeting the criteria for ptsd) for screening ptsd symptoms. kruskal-wallis and mann-whitney tests, as well as multivariate linear regression (using ols), were used for assessing the correlation and identifying the predictors for ptsd symptoms. furthermore, interaction and multi-collinearity (variance inflation factor < 10 or torrance > 0.2) were assessed for the regression final model. adjusted beta coefficients were computed based on 95% confidence intervals. furthermore, model fits were evaluated using scatterplots, homoscedasticity, durbin-watson test, normal p-p plot, qq plot, and cook’s distance values. continuous variables such as age, work experience, number of shifts, and number of missions, and categorical variables such as marital status (single, married, divorced), degree (emergency medical technician, nurse, operation room technician, anesthesia technician), employment status (formal, informal), base location (urban, road, air) were considered as possible independent variables of the model. all statistical analyses were performed using ibm spss statistics version 20 and p <0.05 was considered as the significance level. 3. results in the present study, 259 male emts were recruited for participation in the study after being qualified for the inclusion criteria (figure 1: study flowchart). the mean age of the participants was 32.79 ± 6.16 years (21 52) and their median work experience was 9 years (iqr 5-12). the median number of work shifts and pre-hospital missions in which technicians were deployed in the previous month was 12 (iqr 11-13) and 60 (iqr 9-85), respectively. 53.7% of the emts had previous training on stress control and management. ptsd prevalence in the emts was 22.00%. the mean age of emts in the ptsd-diagnosed group was 28.88 years (sd= 6.94) with mean total pcl-5 score of 38.02 (sd= 6.08), while mean age was 33.77 years (sd= 5.55) and mean total pcl-5 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e35 score was 17.47 (sd = 8.36) in the group without ptsd. the mean total pcl-5 score in all samples was 21.60(sd = 11.45) and ranged from 4 to 50. in addition, the mean total score was 4.98(sd= 3.08), 2.25(sd= 1.70), 7.42(sd= 4.63), and 6.94 (sd= 4.10) for intrusion, avoidance, negative alterations in cognition, and alterations in arousal and reactivity clusters, respectively (table 1). table 2 indicates the mean of each cluster and the total pcl5 score based on personal/work-related characteristics. furthermore, negative alterations in cognition were regarded as the most common cluster symptom and ranged between a score of 2 (19.7%) to 22 (0.4%) based on intensity (6 items with a score between 0-24). as shown in table 1, alterations in arousal and reactivity were the second most common symptoms with the score ranging between 2 (18.1%) and 19 (4.0%) (7 items with a score between 0-28). furthermore, the result of mann-whitney test indicated that the difference between mean score of clusters in ptsd and non-ptsd groups was statistically significant (p<0.001). based on the results, demographic factors such as age (t =41.86, df=2, p<0.001), marital status (t =49.60, df=2, p<0.001) and number of shifts (z= -6.78, p< 0.001) were significantly associated with pcl-5 score (table 2). however, no significant relationship was observed between some factors such as work experience (t =3.01, df=2, p=0.204), number of mission (z= -1.65, p= 0.098), employment status (z= -1.07, p=0.282), base location (t =3.84, df=2, p=0.146), degree (t =0.42, df=3, p=0.935), and previous training history status (z= -0.88, p=0.375) with the total pcl-5 score. after adjusting confounders in multivariate linear regression, the number of missions (t: 2.50, p=0.013) and work experience (t: -3.24, p=0.001) could significantly predict ptsd status. in this regard, the number of shifts per month was the strongest factor (t: 26.38, p<0.001). additionally, no violation of assumptions was observed in the regression model. finally, the linear regression of the final model was significant (f= 297.30, df= 258, p < 0.001), which could explain 77.8% of the variance in the total pcl-5 score (r2 = 0.77). 4. discussion the present study aimed to screen those with ptsd according to dsm-5 criteria and identify its related factors among the studied emts. ptsd prevalence rate among the studied emts was 22.00%. in addition, negative alterations in cognition (m= 7.42) and avoidance (m= 2.25) were the most and least common clusters, respectively. in general, emts with the age of ≤ 30 years, work experience of ≤ 10 years, married status, informal employment, emergency medical technician’s degree, and more than 8 shifts per month, as well as no previous training history had a higher total pcl-5 score. furthermore, the rate of ptsd among the emts in the figure 1: study flowchart. emts: emergency medical technicians. figure 2: simple box plot of correlation between base location and total pcl-5 score; median: number of missions. present study (dsm-5) is considerably high, compared to that of other studies (22). petrie et al., in their systematic review and meta-analysis, showed that the prevalence rate of ptsd (dsm-4) among ambulance staff was 11% (22). fjeldheim et al. reported that 94% of paramedic trainees in a south african university were directly exposed to trauma, and only 16% met the diagnostic criteria for ptsd (23). perhaps, the choice of different instruments and the context are some of the reasons for this variation in the reported prevalence of ptsd. the number of missions conducted by technicians stationed at the road and air bases was less than that of the urban bases, leading to less exposure to prehospital emergencies; yet, no significant difference was observed in the total pcl-5 score this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. khazaei and et al. 4 among the emts stationed at the three above-mentioned bases (p= 0.146) (figure 2). perhaps, technicians who were stationed at the road and air bases have had more exposure to extremely traumatic events and provided high-acuity care in the unstable physical and environmental situations related to these bases such as the long distance between the road base with the first medical center, air turbulences, flight altitude, and the like. presently, ems transports those with a life-threatening condition and requiring critical care to a hospital via air bases. they experience more stress because the roads in iran are considered to have one of the highest rates of accidents in the world and road-based technicians are faced with dangerous accidents leading to more casualties and injuries. the results of the present study were inconsistent with those of schiszler et al., which reported that ground rescue workers are exposed to higher work-related stress compared to the air-ambulance workers (24). based on univariate linear regression, the number of shifts per month has a strong effect on the pcl-5 score so that the total pcl-5 score in the emts increased nearly 0.8% (standardized beta coefficient) in the exchange for doing a shift (24 h). the result is inconsistent with the study of iranmanesh, which indicated that paramedics who work less than 100 hours per month may have a higher rate of ptsd (p=0.001) compared to those working 100–150 or more than 200 hours per month (9). in this regard, shift work sleep disorder (swsd) may be regarded as one of the reasons that can explain the impact of shift work on individuals’ ptsd. swsd is considered a condition resulting from working atypical shifts including nights and long work hours, such as emts’ shifts, leading to the disorder of circadian rhythm and accordingly ptsd symptoms (25, 26). furthermore, age was considered as another factor, which was significantly correlated with the ptsd score as a categorical and continuous variable in the kruskal-wallis (p<0.001) and the univariate linear regression ( β=-0.36, t= -3.19, p=0.02) test. however, it was not regarded as a strong independent predictor of ptsd in the multivariate linear regression analysis. kerai et al. found a negative relationship between age and ptsd symptoms ( β=0.17, p= 0.03) in the linear regression, which indicates a higher prevalence of ptsd in the younger staff (18). in the present study, the ptsd total score in technicians who were less than 30 years was higher than the score in other age groups (table 2). unexpectedly, the total score in the age group of 40 years was higher than that of 31-40 years in the emt. thus, age can be a protective factor against ptsd to a certain level, although a gradual increase in the exposure to the traumatic events over time, irrespective of other important factors such as work experience. based on the results in the study, no significant relationship was observed between work experience as a categorical variable and the total pcl-5 score, while work experience had a protective effect against ptsd in the multivariate linear regression after adjusting others variable (t= -3.23, p=0.001). the result is in line with that of other studies demonstrating the relationship between work experience and ptsd (27, 28). furthermore, a positive correlation was reported between the number of missions and the total pcl-5 score ( β= 0.07) based on the multivariate linear regression after adjusting the variables. the result may reflect the effect of more exposure to traumatic events on ptsd. in another study in south africa, the same relationship was observed between exposure to traumatic incidents and prevalence of mental health problems among emergency medical care personnel (29). in addition, the results are in line with some other studies in which it was reported that ongoing exposure and gaining enough experience simultaneously can increase the technician’s ability to adapt, and develop resilience to stress over traumatic events (30, 31). the history of previous training and psychological debriefing sessions on managing and controlling stress in the prehospital emergency was regarded as another factor which was evaluated in the present study. among the 259 participants, almost 54% had previous training. however, no significant relationship was reported between previous training and the total pcl-5 score (t= -0.83, p=0.319). the results of other studies indicated a considerable difference in the effect of training on reducing the stress among staff. for example, some studies emphasized that regular counseling or defusing sessions, as well as psychological debriefing and critical incident stress management (cism), which is considered as an adaptive and short-term psychological helpingprocess, can prevent ptsd symptoms in personnel (32, 33). however, the results of a systematic review study showed that psychological debriefing has no preemptive effect on the ptsd incidence while cognitive behavior therapy (cbt) for four weeks or more may prevent the development of traumarelated psychological disorders (34). the level of education was another factor whose possible effect on the total pcl-5 score was evaluated (p=0.935) because the personnel’s job in the ems of iran may not be related to the capability, skills, and training they have acquired. alladvanced life support (als) and basic life support (bls) are performed by technicians with the same title (emt), skill, and job responsibilities, which result in varying stress reactions. however, emts are divided into several levels in terms of training and clinical skills they have acquired such as emtb (basic), emt-i (intermediate), and aemt (advanced) (35). for example, minnie et al. reported that emts with a bls and ils qualification find all prehospital emergencies more traumatizing than those with an als qualification, and the difference observed was considerable for road traffic incidents (36). therefore, in these countries, emts are dispatched to basic and advance emergencies in accordance with their this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e35 skills and abilities, which makes the technicians more adaptable in the face of traumatic events, and accordingly they experience less stress than the other emts. finally, the results of the present study suggest that ems authorities should be aware of some modifiable risk factors related to ptsd in order to adopt a proper follow-up and take preventive measures for emts at risk. therefore, conducting a qualitative study to uncover potential stresses in exposure to the variety of prehospital emergency bases is essential. in addition, it is possible to reduce ptsd incidence in emts by changing some factors such as reducing the number of shifts, as well as increasing the staff’s experience by exposing them to traumatic events in a simulated environment. 5. limitations the results of the present study may not be generalizable to other contexts. in the present study individuals who had previously been diagnosed with ptsd or recovered were excluded, which could lead to an underestimation or overestimation of ptsd rate in the present study. also, the findings may be gender biased due because of the lack of female technicians in the pre-hospital system considered as sample in the present study. no study has focused on determining the proper cut-off point for the pcl-5 instrument in the ems staff in an iranian context. hence, the cut-off point used to determine ptsd in the present study may not give an accurate prediction of the participants at risk. variation in estimating the levels of ptsd can be related to the use of different ptsd assessment tools in the prehospital emergency (22). few studies have been conducted using the pcl-5 tool for examining and detecting ptsd among emts. therefore, comparing the results of the present study with other studies may produce some type of bias (39). 6. conclusion the results indicated that the prevalence of ptsd among emt personnel of hamadan province is high. negative alterations in cognition and avoidance were the most and least common clusters, respectively. emts with the age of ≤ 30 years, work experience of ≤ 10 years, married status, informal employment, emergency medical technician’s degree, and more than 8 shifts per month, as well as no previous training history had a higher total pcl-5 score. 7. declarations 7.1. conflict of interest the authors report no conflict of interest and are responsible for the content and writing of the paper. 7.2. acknowledgments abbas mogimbeigi analyzed the data and aided in interpreting the results of the present study. therefore, we would like to thank his for leading to better quality of results. 7.3. funding and support the present project is a part of a phd dissertation supported by tehran university of medical sciences (grant no: 9421199001). 7.4. 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mean total pcl-5 score of each cluster with having or not having post-traumatic stress disorder (ptsd) pcl-5 clusters total ptsd p* no (n = 207) yes (n = 52) intrusion 4.98 (3.08) 4.06 (2.48) 8.67 (2.40) < 0.001 avoidance 2.25 (1.70) 1.85 (1.42) 3.85 (3.62) p<0.001 negative alterations in cognitions 7.42 (4.63) 5.85 (3.40) 13.67 (3.47) p<0.001 alterations in arousal and reactivity 6.91 (4.15) 5.68 (3.44) 11.83 (2.92) p<0.001 *: mann-whitney test. data are presented as mean (standard deviation). table 2: relationship between the personal/work-related characteristics with the total pcl-5 score as well as the mean pcl-5 scores of each cluster characteristics n (%) the mean (sd) pcl-5 cluster scores total p value intrusion avoidance cognition arousal age (years) ≤ 30 92 (35.5) 6.61( 3.26) 2.88 (1.78) 8.92 (5.43) 8.61 (4.49) 27.02 (12.70) 31-40 134 (51.7) 3.73 (2.59) 1.77 (1.49) 6.02 (3.91) 5.50 (3.67) 17.08 (9.42) < 0.001 > 40 33 (12.7) 5.55 (2.03) 2.45 (1.67) 8.91 (2.93) 7.91 (2.81) 24.82 (7.00) work experience (years) ≤ 10 166 (64.1) 5.47 (3.36) 2.42 (1.75) 7.90 (5.13) 7.49 (4.43) 23.31 (12.45) 11-20 89 (34.4) 4.20 (2.92) 2.02 (1.55) 6.69 (3.44) 5.98 (3.41) 18.91 (8.62) 0.204 > 20 4 (1.5) 2.25 (0.5) 0.25 (0.5) 4.00 (2.44) 3.75 (2.06) 10.25 (4.39) marital status single 83 (32) 4.78 (3.03) 2.18 (1.75) 7.27 (4.52) 6.74 (4.21) 21.02 (11.73) maried 171 (66) 5.43 (3.23) 2.40 (1.61) 7.65 (4.89) 7.33 (4.12) 22.81 (11.09) < 0.001 divorced 5 (1.9) 4.60 (1.14) 2.20 (1.70) 8.80 (4.63) 5.80 (4.15) 21.40 (6.34) employment status formal 97 (37.5) 4.43 (2.25) 2.11 (1.63) 7.09 (3.45) 6.49 (3.60) 20.15 (8.86) 0.282 unformal 162 (62.5) 5.31 (3.45) 2.33 (1.74) 7.62 (5.21) 7.16 (4.43) 22.46 (12.70) degree emt 130 (50.2) 5.29 (3.50) 2.50 (1.88) 7.57 (5.03) 6.79 (4.30) 22.20 (12.51) nurse 61 (23.6) 5.11 (3.05) 2.09 (1.65) 7.57 (5.00) 6.86 (4.42) 21.63 (12.68) 0.935 operation 35 (13.5) 4.09 (2.66) 1.97 (1.48) 7.39 (4.01) 6.79 (3.75) 20.30 (9.91) anastesia 33 (12.7) 4.74 (2.16) 1.97 (1.32) 7.03 (3.85) 7.26 (3.94) 21.00 (9.02) base location urban 165 (63.7) 5.17 (3.13) 2.35 (1.76) 7.59 (4.74) 7.23 (4.09) 22.38 (11.22) road 69 (26.6) 4.87 (3.00) 2.14 (1.61) 7.48 (4.75) 6.64 (4.49) 21.13 (12.42) 0.146 air 25 (9.7) 4.08 (3.05) 1.92 (1.52) 6.16 (3.42) 5.56 (3.40) 17.72 (9.54) number of shift (per month) ≤ 8 20 (7.7) 1.80 (1.60) 0.65 (0.98) 2.00 (0.00) 1.80 (0.61) 6.45 (2.11) < 0.001 > 8 239 (92.3) 5.25 (3.03) 2.38 (1.68) 7.78 (4.51) 7.34 (4.03) 22.78 (10.99) number of missions (in the last month) ≤ 80 109 (39.4) 4.71 (3.00) 2.08 (1.52) 7.01 (4.23) 6.43 (4.16) 20.23 (11.34) 0.098 > 80 157 (60.6) 5.17 (3.13) 2.36 (1.80) 7.69 (4.87) 7.22 (4.12) 22.49 (11.47) previous training yes 139 (53.7) 4.76 (3.00) 2.39 (1.69) 7.37 (4.68) 6.53 (3.93) 21.01 (11.25) 0.375 no 120 (46.3) 5.25 (3.17) 2.09 (1.70) 7.48 (4.60) 7.35 (4.36) 22.24 (11.69) sd: standard deviation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e8 or i g i n a l re s e a rc h risk stratification of pulmonary thromboembolism using brain natriuretic peptide and troponin i; a brief report mohsen ebrahimi1, mohammad mohsen arab1, hamid zamani moghadam1, majid jalal yazdi2, esmail rayat doost3, mahdi foroughian1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. department of cardiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. department of emergency medicine, jahrom university of medical sciences, jahrom, iran. received: december 2021; accepted: december 2021; published online: 8 january 2022 abstract: introduction: pulmonary thromboembolism (pte) is one of the most prevalent medical disorders, with a notable annual fatality rate. this study aimed to evaluated the accuracy of serum pro-bnp and troponin i levels in pte diagnosis. methods: this cross-sectional study was implemented on 267 patients with suspected pte (sudden chest pain or sudden dyspnea) in imam reza hospital in mashhad, iran. all patients underwent pulmonary computed tomography (ct) angiography (as the gold standard test) and their serum levels of troponin i and pro-bnp were measured. the screening performance characteristics of pro-bnp in detection of pte cases were measured and reported using receiver operating characteristic (roc) curve analysis. results: two-hundredsixty-seven patients with a mean age of 67.7 ±11.5 years were evaluated (60.1% male). pte was confirmed via ct angiography in 121 patients. the area under the roc curve of troponin i and pro-bnp in detection of pte was 0.501 ng/ml and 0.972 pg/ml, respectively. the sensitivity and specificity of probnp at the best cut-off point (100 pg/ml) were 85.4% and 80.2%, respectively. the sensitivity and specificity of troponin i at the best cut-off point (0.005 ng/ml) were 65.5% and 42%, respectively. conclusion: due to the comparatively good sensitivity and specificity of probnp in diagnosis of pulmonary thromboembolism, it can be employed as a diagnostic determinant in patients with suspected pulmonary thromboembolism along with other laboratory tests. keywords: troponin; pulmonary embolism; natriuretic peptide, brain; computed tomography angiography cite this article as: ebrahimi m, arab m, zamani moghadam h, yazdi m, rayat doost e, foroughian m. risk stratification of pulmonary thromboembolism using brain natriuretic peptide and troponin i; a brief report. arch acad emerg med. 2022; 10(1): e8. https://doi.org/10.22037/aaem.v10i1.1453. 1. introduction pulmonary thromboembolism (pte) can range from being asymptomatic to extensive emboli with a high mortality rate. in the united states, 300,000 people die from pte every year, and in china, pte is much more common than it was 10 years ago (1). smoking cigarette, malignancies, obesity, age, heredity, prolonged comorbidities, and surgical history are introduced as some of the risk factors of pte (2). most ptes are associated with respiratory distress, chest pain, presyncope or syncope, and bloody sputum (3-5). several biomarkers, including pro brain natriuretic peptides (pro-bnp) and cardiac ∗corresponding author: mahdi foroughian; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. email: foroughianmh@mums.ac.ir, tel: 0098+ 9151240686, orcid: http://orcid.org/0000-0002-3944-9361. troponins, have recently been considered for risk stratification of suspected pte cases (6). pro-bnp is mainly secreted from ventricles that are under the stress of altered hemodynamic status and congestive heart failure. pro-bnp is a specific and sensitive indicator for evaluating ventricular function. it is also a suitable indicator for diagnosing heart failure in heart disease (7, 8). kucher et al. showed that pro-bnp higher than 90 pg/ml could predict the risk of mortality as well as need for cardiopulmonary resuscitation and mechanical ventilation in pte patients (9). in a meta-analysis by lega et al., increased pro-bnp and troponin levels were directly related to worse prognosis in pte patients (10). in addition, troponin i and t are known to increase in pte and its levels correlated with mortality rate (11-15). according to the 2014 european society of cardiology (esc) guidelines on the diagnosis and management of acute pulmonary embolism, no studies have yet been performed to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ebrahimi et al. 2 evaluate the appropriate cut-off point for bnp and troponin in diagnosis of pte (16). therefore, this study aimed to evaluated the accuracy of serum pro-bnp and troponin i levels in pte diagnosis. 2. methods 2.1. study design and setting this cross-sectional study was performed on patients with suspected pte, who referred to the emergency department of imam reza hospital, mashhad, iran, from january 2017 to january 2018, to evaluate the diagnostic accuracy of serum troponin i and pro-bnp in detection of at-risk patients for pte. before enrolment of patients, the research process was explained and informed consent was obtained from them. throughout the study, researchers adhered to the principles of the helsinki declaration and the confidentiality of patient information. all costs of the project were covered by the researchers and no additional costs were incurred by the patients. this study was approved by the ethics committee of mashhad university of medical sciences under the ethical code ir.mums.rec.1395. 2.2. participants the study was performed based on the standards for reporting of diagnostic accuracy studies (stard) checklist. the sampling method was non-random and purposive convenience sampling was performed, including all patients who were eligible for study during the study period. patients with sudden shortness of breath and chest pain and positive ddimer levels were included. not agreeing to participate in the study, pregnancy, renal failure, treatment with anticoagulants, myocardial infarction, need for intubation, myocarditis, massive embolism, hypertrophic cardiomyopathy, and negative d-dimer were considered as exclusion criteria. 2.3. procedure after history taking and comprehensive clinical examination of all patients, 5 cc of venous blood was drawn from the brachial vein to assess the serum level of troponin i, using quantitative elisa test kit (diagnostic automation inc. the us), and n-terminal pro-bnp, using clia kit for human (cloud clone, us). the reference standard for pte diagnosis was pulmonary ct angiography. 2.4. data gathering medical record review was performed by mf, me, and mma for assessment of eligibility. medical records belonging to patients with suspected pte, who had undergone ct angiography and whose pro-bnp and troponin levels were available, were considered for data extraction by hzm and mjy using a checklist of study variables. 2.5. statistical analysis patients’ demographic and paraclinical information were coded and entered into spss software version 18. chi-square test was used to analyze the qualitative variables and fisher’s exact test was used if necessary. receiver operating characteristic (roc) curve was used to determine the best cut-off point for pro-bnp and troponin i in diagnosis of pte. p-value less than 0.05 was considered significant. screening performance characteristics of pro-bnp and troponin i at the best cut-off points were calculated and reported. 3. results two-hundred-sixty-seven patients with a mean age of 67.7 ±11.5 years were evaluated (60.1% male). pte was confirmed via pulmonary ct angiography in 121 patients. patients with and without pte were similar regarding age (p = 0.775) and gender distribution (p = 0.28). mean pro-bnp level was 282.6 ± 109.6 pg/ml in pte cases and 49.6 ± 42.3 pg/ml in others (p = 0.001). mean troponin i level in patients with and without pte was 0.04 ± 0.09 and 0.04 ± 0.07 ng/ml, respectively (p = 0475). 3.1. screening performance characteristics the area under the roc curve of troponin i and pro-bnp in detection of at-risk patients for pte was 0.501 ng/ml and 0.972 pg/ml, respectively (figure 1). the best cut-off points of troponin i and pro-bnp in this regard were calculated to be 0.005 ng/ml and 100 pg/ml, respectively. the sensitivity and specificity of probnp at the best cut-off point (100 pg/ml) were 85.4% and 80.2%, respectively. the sensitivity and specificity of troponin i at the best cut-off point (0.005 ng/ml) were 65.5% and 42%, respectively. 4. discussion in this study, we investigated the diagnostic accuracy of probnp and troponin in comparison to ct angiography as the gold standard to estimate the best fitting cut off levels of probnp and troponin in diagnosis of pte. pro-bnp had a sensitivity and specificity of 85.4% and 80.2% for pte prediction in cut off level of 100 pg/ml. while in cut off level of 0.005 ng/ml, troponin i (tpi-i) had low sensitivity and specificity (65.5% and 42%, respectively) in predicting the risk of pte. in line with what we found in our study, in 2009 a metaanalysis by lega et al. showed that elevated bnp and troponin levels were significantly associated with a worse prognosis in pte patients (10). in kucher’s study, the cut-off point of bnp in predicting the occurrence of adverse events in patients with pte was 50 pictograms per ml with 85% sensitivity and 75% specificity (9). in another review study by klok, subjects with acute pulmonary embolism experienced an inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e8 figure 1: the area under the receiver operating characteristic (roc) curve of troponin i (left) and pro-bnp (right) in detection of at-risk cases for pulmonary thromboembolism. crease in bnp levels in 51% of cases. also, a direct relationship was found between increased bnp levels and right ventricular failure (p <0.001). in their study, patients with higher levels of bnp stayed in the hospital for a longer time and had more hospital complications, and also had higher mortality in 30-day follow-up (17). in our study, the diagnostic value of bnp and troponin in acute embolism was investigated and it was shown that an increase in bnp level to greater than 100 pg/ml had a sensitivity and specificity of 85% and 80%, respectively. but troponin had low specificity in diagnosis of acute embolism. it seems that pulmonary thromboembolism can increase bnp by acting on the right ventricle and causing some degree of ventricular failure, which can be used as a diagnostic marker in the acute phase, but the increase in troponin in the acute phase was not significant, as it takes more time for tissue ischemia to be developed. 5. limitations we know that history of previous medical conditions is very important in pte development, so the generalization of our results to all patients with dyspnea and positive d-dimer should be done with caution. 6. conclusion due to the relatively good sensitivity and specificity of probnp in diagnosis of pulmonary thromboembolism, it can be used as a diagnostic factor in patients with suspected pulmonary thromboembolism along with other laboratory tests. 7. declarations 7.1. acknowledgments thanks to mashhad university of medical sciences for supporting and financing this article. also, the clinical research development unit of peymaniyeh hospital of jahrom city is appreciated and thanked for editing this article. 7.2. authors’ contributions me and er conceptualized the study design. mf, me, and mma assessed cases for eligibility. hzm, mjy conducted data collection, me and er analyzed data. all authors contributed in manuscript drafting and revisions. 7.3. funding and supports mashhad university of medical sciences has funded this study. 7.4. conflict of interest the authors of this article did not mention any conflict of interest. references 1. li h-l, chan yc, li n, cui d, cheng sw. prevalence and predictor of pulmonary embolism in a cohort of chinese patients with acute proximal deep vein thrombosis. annals of vascular surgery. 2020;63:293-7. 2. gjonbrataj e, kim jn, gjonbrataj j, jung hi, kim hj, choi w-i. risk factors associated with provoked pulmonary embolism. the korean journal of internal medicine. 2017;32(1):95. 3. miniati m, prediletto r, formichi b, marini c, di ricco g, tonelli l, et al. accuracy of clinical assessment in the diagnosis of pulmonary embolism. american journal of respiratory and critical care medicine. 1999;159(3):86471. 4. pollack cv, schreiber d, goldhaber sz, slattery d, fanikos j, o’neil bj, et al. clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of emperor (multicenter emergency medicine pulmonary embolism in the real world registry). journal of the american college of cardiology. 2011;57(6):700-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ebrahimi et al. 4 5. wells ps, ginsberg js, anderson dr, kearon c, gent m, turpie ag, et al. use of a clinical model for safe management of patients with suspected pulmonary embolism. annals of internal medicine. 1998;129(12):997-1005. 6. daniels lb, maisel as. natriuretic peptides. journal of the american college of cardiology. 2007;50(25):2357-68. 7. hutchinson kr, guggilam a, cismowski mj, galantowicz ml, west ta, stewart jr ja, et al. temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure. journal of applied physiology. 2011;111(6):1778-88. 8. rondelet b, dewachter c, kerbaul f, kang x, fesler p, brimioulle s, et al. prolonged overcirculation-induced pulmonary arterial hypertension as a cause of right ventricular failure. european heart journal. 2012;33(8):101726. 9. kucher n, printzen g, goldhaber sz. prognostic role of brain natriuretic peptide in acute pulmonary embolism. circulation. 2003;107(20):2545-7. 10. lega j-c, lacasse y, lakhal l, provencher s. natriuretic peptides and troponins in pulmonary embolism: a metaanalysis. thorax. 2009;64(10):869-75. 11. lankeit m, friesen d, aschoff j, dellas c, hasenfuß g, katus h, et al. highly sensitive troponin t assay in normotensive patients with acute pulmonary embolism. european heart journal. 2010;31(15):1836-44. 12. giannitsis e, katus ha. risk stratification in pulmonary embolism based on biomarkers and echocardiography. circulation. 2005;112(11):1520-1. 13. meyer t, binder l, hruska n, luthe h, buchwald ab. cardiac troponin i elevation in acute pulmonary embolism is associated with right ventricular dysfunction. journal of the american college of cardiology. 2000;36(5):16326. 14. pruszczyk p, bochowicz a, torbicki a, szulc m, kurzyna m, fijałkowska a, et al. cardiac troponin t monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism. chest. 2003;123(6):1947-52. 15. macrea m. cardiac troponin t monitoring and acute pulmonary embolism. chest 2004; 126: 655-656. 16. members atf, konstantinides sv, torbicki a, agnelli g, danchin n, fitzmaurice d, et al. 2014 esc guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (esc) endorsed by the european respiratory society (ers). european heart journal. 2014;35(43):3033-80. 17. klok fa, mos ic, huisman mv. brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. american journal of respiratory and critical care medicine. 2008;178(4):425-30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e52 or i g i n a l re s e a rc h factors affecting pre-hospital and in-hospital delays in treatment of ischemic stroke; a prospective cohort study neda ghadimi1, nasrin hanifi1, mohammadreza dinmohammadi1∗ 1. school of nursing and midwifery, zanjan university of medical sciences, zanjan, iran. received: may 2021; accepted: june 2021; published online: 24 july 2021 abstract: introduction: the outcomes of acute ischemic stroke (ais) are highly affected by time-to-treatment. the present study aimed to determine the factors affecting in-hospital and pre-hospital delays in treatmentof ais. methods: this prospective study was carried out on 204 ais patients referring to the stroke care unit in zanjan (iran) in 2019. the required data were collected by interviewing the patients and families and using patients’ records and observations. results: the maximum delay was related to onset-to-arrival time (288.19 ± 339.02 minutes). the logistic regression analysis indicated a statistically significant decline in the treatment delay via consultation after the initiation of symptoms (p< 0.001), transferring the patient through emergency medical service to the hospital (p<0.001), and patients’ perception regarding ais symptoms (p< 0.001). conclusion: it is essential to inform people regarding ais symptoms and referring to ais treatment units to reduce the treatment time. keywords: ischemic stroke; time-to-treatment; prospective studies; iran cite this article as: ghadimi n, hanifi n, dinmohammadii m. factors affecting pre-hospital and in-hospital delays in treatment of ischemic stroke; a prospective cohort study. arch acad emerg med. 2021; 9(1): e52. https://doi.org/10.22037/aaem.v9i1.1267. 1. introduction stroke is one of the most prevalent neurological complications (1). acute ischemic stroke (ais) is a medical emergency that requires intensive treatment and care in the early hours, because its fast diagnosis and proper interventions can lead to favorable results. furthermore, delayed treatment can lead to considerable complications, higher mortality, and enormous costs for the person, families, and the healthcare system (2). the most effective approaches to treating ais patients are recanalization and reestablishing blood flow to the brain tissues using invasive and non-invasive therapies (3). in these processes, the blocked vessels are reopened using recombinant tissue plasminogen activator (rtpa) and mechanical devices (angioplasty) (4, 5). in 1996, the food and drug administration (fda) recommended using rtpa in ais patients within the first 3 h of symptoms onset (6). american stroke association standard (2018) recommends brain imaging within less than 20 min, the interval of less than 60 min ∗corresponding author: nasrin hanifi; zanjan nursing and midwifery school, zanjan university of medical sciences, shahrak-e karmandan street, zanjan, iran. p.o. box:45154-13191, email: nasrinhanifi@zums.ac.ir, tel: 02433148336, https://orcid.org/0000-0002-4027-2399. between the hospital arrival, and thrombolytic therapy for over 50% of patients qualified for rtpa (7). research has shown that rtpa is avoided as it wastes the golden time of medication use due to the delayed arrival at the hospital (8). the time-to-treatment delay in ais patients may be caused by different factors such as pre-hospital and intra-hospital reasons. delays in recognizing and transfer of patients are among the pre-hospital causes of their mortality. meanwhile, delays in neurologic visits, delays in decisionmaking regarding the treatment procedure, and delays in brain imaging are considered among the intra-hospital delay causes (9, 10). treatment delay is a function of several factors, including the patient’s delay after the onset of early symptoms and delay by treatment staff (11, 12). lack of access to medical centers (13) and lack of proper management of ais patients in the hospital are among the factors influencing the time-to-treatment delay (14, 15). in this respect, code 724 has been effective in reducing the delay in treating ais patients (16). in iran, the stroke code (code 724) was announced by iran’s ministry of health to the medical universities in 2016 to treat stroke patients more effectively. thus, in addition to implementing this plan, it is essential to review the status of prehospital and hospital delays in stroke care units (scu) in iranian cities. in every community, it is essential to investigate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. ghadimi et al. 2 the factors influencing pre-hospital and in-hospital delay, the quality of care delivered, and the individual factors affecting timely treatment. these influencing factors can vary from community to community. the present study aimed to determine the factors influencing in-hospital and pre-hospital delays in treatment of ais. 2. methods 2.1. study design and setting this cross-sectional descriptive study was performed in the scu of vali-asr hospital, zanjan (northwest of iran), from july to the end of october 2019. ais cases or their relatives were interviewed about potentioal causes of delay in initiation of thrombolytic therapy using a predesigned questionnaire (appendix 1). the ethics committee of zanjan university of medical sciences approved this study under the ethics code ir.zums.rec.1398.095. the researcher described the study’s aims to the patients or their families, and written consent was obtained. the participants were assured about the confidentiality of all their information and the right to leave the study at any time. 2.2. participants the samples were collected using convenience sampling. therefore, the study participants included patients referring to the scu during the sampling interval, who met the inclusion criteria. the physician confirmed the diagnosis of ais based on clinical signs and brain ct-scan results. willingness to participate in the study was considered the inclusion criterion. patients diagnosed with a hemorrhagic stroke or transient ischemic attack (based on ct-scan results) were excluded from the study. 2.3. procedure scu of vali-asr hospital in zanjan, was established in 2016 and is known as the stroke referral center in zanjan province. in iran, code 724 refers to stroke patients whose stroke symptoms have initiated less than 4 hours and 30 minutes before. based on this code, as soon as the patients call the emergency medical services (ems), they are asked about the facearms-speech-time (fast) symptoms. then, after the ambulance is sent to the patient’s bedside, the emergency technician examines the fast symptoms, and need to scu is reported followed by confirmation. patients from the neighboring provinces are immediately transferred from all medical centers to the scu in zanjan. after transferring the patient to the hospital, a neurologist examines them at the triage unit and sends him/her to the brain computed tomogramphy (ct) scan if the diagnosis of a stroke is made based on the scan, the rtpa medication is administered there. 2.4. data gathering the variables in this study included demographic characteristics, factors affecting the time of treatment initiation in both in-hospital and pre-hospital phases, and stroke risk factors (hypertension, hyperlipidemia, smoking, and diabetes). a questionnaire was used to collect the data and identify the information on demographic features and factors affecting time-to-treatment and the average time between onset of symptoms to treatment (7, 11, 17-20). the questionnaire included three parts. questions about the demographic features of the patients were included in the first part. the second part contained questions regarding the causes of prehospital delays. the third part included questions about the reasons for in-hospital delay (appendix 1). these data were approved by the treating physician. to assess ais severity, we considered the national institutes of health stroke scale (nihss) (21). this scale includes 11 items, for which a score of 0 denotes the individual’s normal performance in the studied field, and a score of 4 represents maximum impairment in that field. the maximum and minimum scores on this scale are 42 and 0, respectively. in this regard, the score 0 denotes lack of stroke symptoms, 1 to 4 is mild stroke, 5-15 is moderate stroke, 16-20 is moderate to severe stroke, and 21-42 denotes severe stroke. the content validity of the questionnaire was evaluated. the designed questionnaire was offered to 10 experts to make the essential modifications and alterations they believed to be necessary. its reliability was assessed using inter-rater relaibility. two researchers completed the questionnaire for the same 10 patients, simultaneously. then, cohen’s kappa coefficient was assessed between the data of the researchercompleted questionnaires, and the evaluators’ reliability was confirmed by achieving k = 0.973. the reliability and validity of the nihss tool had been confirmed by kasner et al. (21). the data were collected through observation and interviews with patients and their families, if necessary. the patients referring to the scu were chosen based on the inclusion criteria. the researcher completed the questionnaire after treatment and relative stabilization of the patient with the assistance of the patient or his/her caregivers. in this study, to reduce recall bias regarding the timing of the events by the patients and their families, and recording the times and factors influencing pre-hospital delays as accurately as possible we highlighted the critical times like news time, azan time, and events of the day when asking about the events . 2.5. data analysis according to a pilot study on 20 ais patients, we considered a sample size of 181, an effect size of 0.05, a sampling error of 20 min, and a confidence level of 95%. in this study, 204 patients with ais referring to the scu were assessed. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e52 statistical analyses were performed using spss v.16 software. the data were distributed based on the normalized central limit theorem. data were gathered through interviews and observations. for detecting the predictors of delay to treatment, a logistic regression model was performed using the forward-lr method. to determine the factors affecting time-to-treatment, variables including age (age less than 60 years and age over 60 years), gender, previous history of stroke, calling ems, consultation after the onset of symptoms, and patient’s perception of early symptoms were entered to the model as independent variables. in contrast, delay in treatment was used as the dependent variable. in this study, the significance level was considered less than 0.05. there was no missing data in the present study, because the researchers collected data through interviews, observations, and patient records. 3. results 3.1. baseline characteristics of participants this study was conducted on 230 patients with stroke referring to the scu from early july to late october 2019. the data of 16 patients with transient ischemic attack and 10 patients with hemorrhagic stroke were excluded from the study. ultimately, the data of 204 patients with acute ischemic stroke who had referred to the scu were assessed. the treating physician diagnosed the ischemic stroke in these patients. in total, 204 patients were included in this study, 55.9% of which were male, 19.6% had a high school diploma, and 72.5% were illiterate. the participants’ mean age was 68.99 ±13.91 (28 98) years. fifty percent of the patients lived in zanjan. according to patients’ statements, 87.7% had at least one risk factor. hypertension (59.3%) was the most prevalent risk factor for ais, and ischemic heart disease was in the second rank (30.4%). moreover, about 77.9% of the patients were at home when the symptoms had initiated. the severity of the stroke was moderate in 52% of the patients. in this study, 140 (68.6%) patients were referred to the scu with code 724. they arrived at the hospital within less than 4 hours (h) and 30 minutes (min) after the onset of symptoms. moreover, rtpa was provided for 129 (63.2%) patients, but it was not used for 75 (36.8%) patients. 3.2. analysis of delay to treatment the reason for not receiving rtpa in 64 (31.4%) patients was that more than 4 hours and 30 minutes had passed from the symptoms’ onset to referral to scu. table 1 shows the frequency of potentioal prehospital causes of delay in treatment of ais cases. 70.6% of the patients considered their prime symptoms to be symptoms of other diseases and did not believe they had a stroke. furthermore, 17.2% had no consultation with anyone after the onset of the symptoms and took no action. after the onset of symptoms, about 47.5% of the patients referred to medical centers rather than scu. it is noteworthy that they mostly (30.4%) referred to these centers because of availability or proximity. 46.1% of them referred to scu using personal vehicles. a neurologist performed the first visit for more than half of the patients (62.7%). the mean onset-to-arrival time and the mean onset-to-treatment time were 288.19 ± 339.02 minutes and 314.13 ± 341.04 minutes, respectively. table 2 shows the time interval between onset of symptoms and treatment based on pre-hospital and in-hospital factors. among the pre-hospital delay factors, the delay in deciding to contact the emergency service or making the effort to refer to medical centers (204.74 ± 321.38 minutes) was longer compared to the time of patient transfer to the hospital (83.52 ±72.38 minutes). in identifying the predictors of delay in treatment, among the predictor variables included in the model, calling ems, patient’s perception of early symptoms, and consultation after the onset of symptoms could effectively predict this delay. the odds of decreasing the delay in treatment for transportation by ems, patient’s perception of early symptoms, and consultation after the onset of symptoms were 0.12 (95%ci: 0.033-.435), 7.46 (95%ci: 2.04-27.3), and 0.008 (95%ci: 0.0010.05), respectively (table 3). 4. discussion our results indicated that pre-hospital delay was longer compared to the hospital delay. the delays in making the effort to refer to the medical center or the decision to call the emergency service were longer compared to the time of patient transfer to the hospital. in a study in hamadan (iran), ghiasian et al. reported that the time interval between symptom onset to arrival at the hospital was 282 min, while it was 192 min in the study of griesser et al (11, 22). this result is consistent with the findings of our study. nevertheless, in the study of ayromlou et al. in tabriz (iran), this time was 916 min, which is not in line with our results (13). in the mentioned study, which was conducted in the metropolitan area of tabriz, the delay in patients’ arrival could be caused by traffic problems in this city. in the smaller towns around the provinces equipped with scus, accurate diagnosis of the stroke, the existence of neurologists, and administering thrombolytic medication can dramatically decrease the onset-to-treatment time. koksal et al., ruiz et al., faiz et al., sobral et al., springer et al., and haiqiang et al. showed that access to transfer with ems shortens the delay in hospital arrival (12, 17, 19, 23-25). in our study, also, less delay was experienced by the patients referring via ems. consistent with our study, the findings of studies conducted in america, asia, and europe indicated this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. ghadimi et al. 4 table 1: the frequency of potential pre-hospital causes of delay in initiation of treatment for patients with acute ischemic stroke variables number (%) variables patient’s perception of early symptoms neurologic 60 (29.4) non-neurologic 144 (70.6) consultation after the onset of symptoms spouse 49 (24.0) children 94 (46.0) colleague 4 (2.0) relatives 18 (8.8) nurse 4 (2) not consulting anyone 35 (17.2) center visited after symptom onset scu in zanjan 107 (52.5) other medical centers 55 (27.0) clinic 28 (13.6) private office 13 (6.4) private hospital 1 (0.5) reasons for not referring toscu proximity or availability of another center 62 (30.4) not being aware of stroke center at scu 8 (3.9) not considering the disease seriously by the patient 27 (13.2) referred to hospital by personal vehicle 94 (46.1) emergency medical services (ems) 64 (31.4) ambulance from other medical centers 44 (21.5) stroke inside the hospital 1 (0.5) air emergency 1 (0.5) the first visitor of the patient general practitioner 2 (1.0) resident of neurology 128 (62.7) emergency medicine specialist 68 (33.3) neurologist 5 (2.5) non-neurology resident 1 (0.5) scu: stroke care unit. that absence of awareness of stroke symptoms, patients’ beliefs and misconceptions about the prime symptoms, and failure to consult an individual after the onset of the symptoms resulted in longer delays in hospital arrival and timeto-treatment for stroke patients (11, 12, 17, 19, 22-27). the results indicate that consulting with others after initiation of the symptoms may help prevent a delay in cases the symptoms of the patients are not well-recognized or taken seriously. the results of our investigation on factors causing hospital delay in ais patients revealed that there were no delay for ais patients receiving code 724. in this study, the time interval between hospital arrival to rtpa implementation (25.18 ±17.01 min) and between hospital arrival to brain ct scan (10.60 ± 6.79 min) was much shorter compared to the time proposed by the american stroke association guidelines (7). in the study by dhaliwal et al. in the us, the mean initial ct table 2: the time interval between onset of symptoms and treatment based on pre-hospital and in-hospital factors variables mean ± sd pre-hospital time intervals (minutes) onset –todecision time 204.74 ± 321.4 the transfer time 83.52 ± 72.4 onset –toarrival time 288.19 ± 339 in-hospital time intervals (minutes) door –to –examination time for with code 724 3.07 ± 2.5 door –to –examination time for without code 724 15.08 ± 8.5 door –to –scu entry time for with code 724 17.99 ± 13.1 door –to –scu entry time for without code 724 216.98 ± 173.5 door –to –imaging time for with code 724 10.6 ± 6.9 door –to –treatment decision making for with code 724 21.87 ± 13.9 door–to –order time for with code 724 23.08 ± 16.5 door –to –needle time for with code 724 25.01 ± 17 door –to – treatment time for without code 724 29.07 ± 33.8 onset –to –treatment time in stroke patients 314.13 ± 341 sd: standard deviation; scu: stroke care unit. scan time was 13.66 min, the ct scan interpretation time was 25.20 min, and the time between the arrival of the patients and rtpa injection was 51.27 min (15). hasankhani et al. in tabriz (iran) found that the mean time between hospital arrival and rtpa injection is 69 min (14). in the study of mowla et al. in new york, the maximum imaging delay was longer than 25 min (28). according to the findings obtained in iran and other countries, the time interval between hospital arrival and treatment in patients with code 724 is much longer compared to our results. this indicates that the management of the stroke code team in zanjan city have been able to significantly shorten time-to-treatment. 5. limitations the low accuracy of recalling the times, particularly in elderly patients, was among the limitations of this study. the researchers tried to record the times and factors influencing pre-hospital delays as accurately as possible by highlighting the critical times like news time, azan time, and events of the day. considering the geographical and cultural position of zanjan, the present results cannot be generalized to other communities. 6. conclusion in the present study, a longer pre-hospital delay was found compared to hospital delay in stroke events. among the prehospital delay factors, the delay in visiting a medical center or this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e52 table 3: indipendent predictors of delay in treatment of acute ischemic stroke cases variables logistic regression analysis b s.e wald df p exp(b) consultation after the onset of symptoms 4.536 917 24.468 1 0.001 0.008 transportation by ems 2.369 0.646 13.433 1 0.001 0.12 patient’s perception of early symptoms -1.565 0.536 8.532 1 0.003 7.46 constant -2.796 0.627 19.886 1 0.001 8.92 b=beta, s.e= standard error, df=degrees of freedom, exp (b)= ecpected beta; *p-value< 0.05. deciding to call the ems was longer than the time of patient transfer to the hospital. in other words, a more significant portion of the delays in the pre-hospital phase is caused by the delay in patients’ decision to refer to the hospital. it appears that giving information to at-risk people, particularly those over 60 years, about the stroke risk factors, the importance of rapidly initiating treatment to enhance the disease outcomes, and the early stroke symptoms will help patients comprehend their symptoms properly. hence, they will be transferred to the hospital faster by calling the emergency system. 7. declarations 7.1. acknowledgments this study is based on a research project with the code a-11148-19. here, the researchers thank the research participants for their cooperation and zanjan university of medical sciences vice-chancellor for financial support. 7.2. funding and support this article results from a master of nursing thesis funded by the research department of zanjan university of medical sciences. 7.3. author contribution nh designed the study, carried out statistical analyses of the data, was involved in interpreting the data, and wrote the manuscript. ng, who also collected the data, was involved in the interpretation of the data. mr d was involved in the interpretation of the data. all authors read and approved the final manuscript. 7.4. competing interests the authors declare that they have no competing interests. 7.5. pre print this article part of this article on the site research sequare is online as pre print. available in: https://www.researchsquare.com/article/rs135115/v1 doi: 10.21203/rs.3.rs-135115/v1 references 1. ropper ah. adams and victor’s principles of neurology: mcgraw-hill medical pub. division new york; 2005. 2. bernaitis n, anoopkumar-dukie s, bills s, crilly j. evaluation of adult stroke presentations at an emergency 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oaa, elhassanien me. stroke onset to needle delay: where these golden hours are lost? an egyptian center experience. eneurologicalsci. 2019;14:68-71. 27. sharma m, helzner e, sinert r, levine sr, brandler es. patient characteristics affecting stroke identification by emergency medical service providers in brooklyn, new york. internal and emergency medicine. 2016;11(2):22936. 28. mowla a, doyle j, lail ns, rajabzadeh-oghaz h, deline c, shirani p, et al. delays in door-to-needle time for acute ischemic stroke in the emergency department: a comprehensive stroke center experience. journal of the neurological sciences. 2017;376:102-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e52 appendix 1: tia: transient ischemic attack; ocp: oral contraceptive; mi: myocardial infarction; chf: chronic heart failure; ihd: ischemic heart disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. ghadimi et al. 8 appendix 2: ems: emergency medical services; scu: stroke care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e52 appendix 3: bs: blood sugar; nihss: nih stroke scale; pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio; scu: stroke care unit; ct: computed tomography; ich: intracranial hemorrhage; tia: transient ischemic attack; sah: subarachnoid hemorrhage; cvt: cerebral venous thrombosis; tpa: tissue plasminogen activator. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e25 or i g i n a l re s e a rc h glasgow coma scale versus physiologic scoring systems in predicting the outcome of icu admitted trauma patients; a diagnostic accuracy study sorour khari1, mitra zandi2∗, mahmoud yousefifard3 † 1. student research committee, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 3. physiology research center, iran university of medical sciences, tehran, iran. received: february 2022; accepted: march 2022; published online: 9 april 2022 abstract: introduction: there is no consensus on the performance of decision rules in predicting the prognosis of trauma patients. therefore, the present study aimed to compare the value of glasgow coma scale (gcs) and physiologic scoring systems in predicting mortality and poor outcome of trauma patients. methods: this diagnostic accuracy study was conducted on multiple trauma patients admitted to the intensive care units of two hospitals in tehran, iran, from 21 november 2020 to 22 may 2021. the patients’ demographic characteristics, length of stay in the intensive care unit (icu), the vital signs, and the gcs on admission were recorded. finally, the mortality, disability, and complete recovery of patients at the time of discharge were evaluated and receiver operating characteristics (roc) curve analysis was used to compare the performance of physiologic scoring systems with gcs. results: 200 trauma patients with the mean age of 43.53±19.84 years were evaluated (74% male). the area under the roc curve for new trauma score (nts), revised trauma score (rts), worthing physiological scoring system (wpss), rapid acute physiology score (raps), rapid emergency medicine score (rems), modified early warning score (mews), national early warning score (news), glasgow coma scale, age, and systolic blood pressure score (gaps) ,glasgow coma scale (gcs) in prediction of mortality were 0.95, 0.95, 0.83, 0.89, 0.91, 0.84, 0.77, 0.97, and 0.98 respectively. the performance of gcs was statistically superior to rts (p=0.005), wpss (p=0.0001), raps (p=0.0002), rems (p=0.002), mews (p<0.0001), and news (p<0.0001). however, the performance of gcs, nts (p=0.146), and gaps (p=0.513) were not significantly different. also, in prediction of poor outcomes, the auc of gcs (0.98) was significantly higher than rts (0.95), raps (0.85), rems (0.85), mews (0.84), news (0.77), and wpss (0.75). conclusion: the gcs score seems to be a better instrument to predict mortality and poor outcome in trauma patients compared to other tools due to its high accuracy, wide application, and easy calculation. keywords: wounds and injuries; clinical decision rules; patient outcome assessment; glasgow coma scale; intensive care units cite this article as: khari s, zandi m, yousefifard m. glasgow coma scale versus physiologic scoring systems in predicting the outcome of icu admitted trauma patients; a diagnostic accuracy study. arch acad emerg med. 2022; 10(1): e25. https://doi.org/10.22037/aaem.v10i1.1483. ∗corresponding author: mitra zandi; school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran.e-mail: mitra.zandi@yahoo.com, tel: +98-21-88202511, orcid: http://orcid.org/00000002-7395-0280. † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran. email: yousefifard.m@iums.ac.ir / yousefifard20@gmail.com, phone/fax: +982186704771, orcid: http://orcid.org/0000-0001-5181-4985. 1. introduction trauma is one of the most well-known external injuries that remain a worldwide public health concern. according to statistics, 16% of the global burden of diseases is related to injuries, and approximately 4.5 million deaths are caused by traumatic injuries annually (1, 2). furthermore, lower-middle-income countries sustain 90% of injuryrelated deaths (2). based on the who reports, the common causes of traumas are traffic accidents, falling from a height, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khari et al. 2 occupational injuries, and personal accidents. road traffic accidents will be the fifth major cause of death globally by 2030 (3, 4). traumatic injuries are the first reason for losing years of potential life and one of the four leading causes of mortality in developing countries (5). the consequences of traumatic injuries are affected by the trauma severity, the physiological reserve, the on-time revival, and appropriate treatment (6). patients with severe trauma need hospitalization in the intensive care unit (icu). trauma-related death in patients admitted to the icu is caused by severe brain injury and multiple organ failure (7). management, timely post-traumatic care, and creating specific care systems at trauma centers are vital for reducing the mortality rate, disability risk, and longterm pain in traumatic patients (8, 9). with the increase in health care costs and the shortage of beds in intensive care units, patients should be appropriately triaged to avoid unnecessary costs and the use of beds (10). in recent years, several scoring systems have been designed to assess injury severity and determine which patients need observation, treatment, and allocation of health care resources (11, 12). although improvements have been made to multiple scoring systems, each system still has its limitations and shortcomings, including many variables in the model, failure to evaluate them in different clinical settings, and complex calculations required to conclude (11, 13). the physiological scoring systems are helpful for treatment staff to recognize the severity of trauma and decide the period of trauma management (9). in all of these scoring systems, in addition to the level of consciousness, physiological criteria such as respiration rate, body temperature, heart rate, and blood pressure are used to determine the severity of trauma injury (14). new trauma score (nts), revised trauma score (rts), worthing physiological scoring system (wpss), rapid acute physiology score (raps), rapid emergency medicine score (rems), modified early warning score (mews), national early warning score (news), glasgow coma scale, age, and systolic blood pressure (gaps) are some of these scoring systems. glasgow coma scale (gcs) is a valuable, rapid, and accurate method to determine patients’ injury severity, consciousness level, and outcome, especially in those with a head injury, and has remained an important method for assessing critically injured patients in the middle east region and iran (5-9, 14, 15). there are conflicting results from comparing gcs with scoring systems in predicting patient outcomes. the existence of contradictions indicates the need for more studies. accordingly, this study was designed to compare the performance values of eight physiologic scoring systems including nts, rts, wpss, raps, rems, mews, news, and gaps, with gcs in predicting poor outcome and mortality of trauma patients admitted in icu. 2. methods 2.1. study design and setting this prospective diagnostic accuracy study was carried out between 21 november 2020 and 22 may 2021 at icus of two hospitals in tehran, iran. the present study obtained ethical approval from shahid beheshti university of medical sciences (ir.sbmu.pharmacy.rec.1399.243). the researchers adhered to the declaration of helsinki regarding the ethical issues and confidentiality of patients’ information. 2.2. participants the population study included 200 trauma patients admitted to the intensive care units (icus). the researcher selected patients using the convenience sampling method. the inclusion criteria were admission to icu due to traumatic injuries and age over 18 years. the exclusion criteria included pregnancy and transferring patients to other centers. 2.3. data gathering the researcher filled out the pre-prepared checklist in each hospital on admission, including age, gender, trauma mechanism, co-morbidities, vital signs on admission, alert, voice, pain, unresponsive (avpu) scale, and glasgow coma scale. vital signs for each patient were as follows: heart rate, respiratory rate, temperature, systolic blood pressure, diastolic blood pressure, mean arterial pressure, oxygen saturation. the variables such as age, mean arterial pressure, heart rate, respiratory rate, temperature, and oxygen saturation were used to evaluate the eight values of physiologic models. the glasgow coma scale (gcs) is the sum of the three tests of the patient’s eye-opening, verbal, and motor responses with a minimum score of 3 and a maximum of 15 (16). the national early warning score (news) is based on seven simple physiological variables (systolic blood pressure, body temperature, respiration rate, oxygen saturation, heart rate, level of consciousness, and supplemental oxygen). the scoring is from 0-20 (17). the modified early warning score (mews) includes five variables: systolic blood pressure, heart rate, body temperature, respiration rate, and level of consciousness. the score ranges from 0 to a maximum of 14 (12). the rapid emergency medicine score (rems) is determined using age and five physiological variables including heart rate, mean blood pressure, respiration rate, oxygen saturation, and glasgow coma scale. the highest score is 26 (12). the rapid acute physiology score (raps) consists of heart rate, respiration rate, blood pressure, and glasgow coma scale. its scoring range is 0 (normal) to 16 (acute) (13, 18). the worthing physiological scoring system (wpss) consists of six parameters: systolic blood pressure, heart rate, respirathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e25 table 1: comparing the baseline characteristics of included patients based on their survival status and outcome variables survival p outcome p yes (n=163) no (n=37) good(n=125) poor(n=75) age (year) 41.28±18.72 53.40±21.80 <0.0001 41.33±18.59 47.18±21.39 0.043 gender male 120 (73.6) 28 (75.7) 0.797 91 (72.8) 57 (76.0) 0.617 female 43 (26.4) 9 (24.3) 34 (27.2) 18 (24.0) trauma mechanism motorcycle 49 (30.1) 10 (27.0) 36 (28.8) 23 (30.7) car accident 35 (21.5) 8 (21.6) 27 (21.6) 16 (21.3) bicycle 5 (3.1) 0 (0.0) 0.766 5 (4.0) 0 (0.0) 0.341 pedestrian 27 (26.5) 4 (10.8) 23 (18.4) 8 (10.7) fall >3m 6 (16.2) 20 (12.3) 13 (10.4) 13 (17.3) fall <3m 27 (16.6) 9 (24.3) 21 (16.8) 15 (20.0) co-morbidities hypertension 44 (27.0) 14 (37.8) 0.189 34 (27.2) 24 (32.0) 0.619 diabetes 34 (20.9) 7 (18.9) 0.792 27 (21.6) 14 (18.7) 0.469 cvd 8 (21.6) 25 (12.5) 0.063 15 (12.0) 10 (13.3) 0.783 pd 25 (15.3) 8 (21.6) 0.353 19 (15.2) 14 (18.7) 0.523 other 19 (11.7) 5 (13.5) 0.754 16 (12.8) 8 (10.7) 0.653 glasgow coma scale 3-8 24 (14.7) 37 (100.0) 1 (0.8) 60 (80.0) 9-12 38 (23.0) 0 (0.0) <0.0001 24 (19.2) 14 (18.7) <0.0001 13-15 101 (62.0) 0 (0.0) 100 (80.0) 1 (1.3) vital signs on admission hr (/min) 99.46±21.34 86.40±28.95 <0.0001 99.05±21.04 93.70±26.72 0.118 rr (/ min) 19.20±4.37 17.67±4.03 0.052 19.49±4.39 17.97±4.12 0.016 t (°c) 36.71±2.43 36.82±0.70 0.781 36.69±2.76 36.79±0.63 0.749 sbp (mmhg) 124.09±22.50 105.32±26.88 <0.0001 125.76±21.18 112.05±27.07 <0.0001 dbp (mmhg) 78.86±17.71 64.05±14.18 <0.0001 79.68±17.38 70.2±17.63 <0.0001 map (mmhg) 91.46±19.40 77.11±17.93 <0.0001 92.73±19.60 82.25±18.75 <0.0001 sao2 (%) 96.20±7.17 95.32±4.75 0.479 95.90±8.07 96.26±3.81 0.715 length of stay in icu (days) mean ± sd 5.77±5.30 7.56±7.30 0.086 4.59±3.14 8.62±7.87 <0.0001 data are presented as mean ± standard deviation (sd) or number (%). these data were evaluated at the time of admission to intensive care unit (icu). the outcome variables were patient survival status (survived, died), good outcome (complete recovery), and poor outcome (mortality, disability). cvd: cardiovascular disease; pd: pulmonary disease; hr: heart rate; rr: respiratoty rate; t: temperature; sbp: systolic blood pressure; dbp: diastolic blood pressure; map: mean arterial pressure; sao2: saturation o2. tion, body temperature, level of consciousness, and oxygen saturation. its maximum score is 14 (19, 20). the revised trauma score (rts) includes the systolic blood pressure, glasgow coma scale, and respiration. the final score of this tool is in the range of 0-12 (21). the new trauma score (nts) system is a new physiological scoring tool, it is a modified version of the revised trauma score (rts). this scoring system includes physiological variables (glasgow coma scale, systolic blood pressure, and oxygen saturation level). the scoring method is that the glasgow coma scale (gcs) score is added to the scores of the other two parameters, and the total score ranges from 3 to 23 (22). the glasgow coma scale, age, and systolic blood pressure score (gaps) is a physiological scoring system with a small number of parameters: glasgow coma scale, blood pressure, and age. its score varies from 3-24 (23). 2.4. outcomes the researcher recorded the patient’s status at the time of discharge from icu as an outcome assessment. the outcome variables were patient survival status (survived, died), good outcome (complete recovery), and poor outcome (mortality, disability). 2.5. statistical analysis we assessed the normality assumption of data based on the histograms and kolmogorov–smirnov test. descriptive statistics were means ± sds for continuous variables and frequency (percentage) for categorical variables. the independent sample t-test and fisher’s exact test were conducted to compare the variables between survivors and non-survivors. then, the receiver operating characteristic (roc) curve analthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khari et al. 4 table 2: performance of physiologic scoring systems and glasgow coma scale in prediction of mortality in intensive care unit (icu) admitted trauma patients score cp tp tn fp fn sensitivity specificity ppv npv plr nlr gcs 9 37 133 30 0 100(90.5-100) 81.6(74.8-7.2) 55.2(42.6-67.4) 100(97.3-100) 5.43(3.9-7.5) 0 gaps 18 35 147 16 2 94.6(81.8-99.3) 90.2(84.5-94.3) 68.6(54.1-80.9) 98.7(95.2-99.8) 9.64(6.01-15.4) 0.06(0.02-0.2) nts 14 36 145 18 1 97.3(85.8-99.9) 89.0(83.1-93.3) 66.7(52.5-78.9) 99.3(96.2-100) 8.81(5.7-13.7) 0.03(0.0-0.2) rts 7 37 131 32 0 100(90.5-100) 80.4(73.4-86.2) 53.6(41.2-65.7) 100(97.2-100) 5.09(3.7-6.9) 0 mews 4 35 84 79 2 94.6(81.8-99.3) 51.5(43.6-59.4) 30.7(22.4-40.0) 97.7(91.9-99.7) 1.95(1.6-2.3) 0.10(0.03-0.4) news 5 36 48 115 1 97.3(85.8-99.9) 29.4(22.6-37.1) 23.8(17.3-31.4) 98.0(89.1-99.9) 1.38(1.2-1.5) 0.09(0.01-0.6) wpss 4 31 100 63 6 83.8(68.0-93.8) 61.3(53.4-68.9) 33.0(23.6-43.4) 94.3(88.1-97.9) 2.17(1.7-2.7) 0.26(0.1-0.5) rems 6 31 132 31 6 83.8(68.0-93.8) 81.0(74.1-86.7) 50.0(37.0-63.0) 95.7(90.8-98.4) 4.41(3.1-6.2) 0.20(0.10-0.4) raps 4 32 123 40 5 86.5(71.2-95.5) 75.5(68.1-81.9) 44.4(32.7-56.6) 96.1(91.1-98.7) 3.52(2.6-4.7) 0.18(0.08-0.4) data are presented with 95% confidence interval. cp: cut off point; tp: true positive; tn: true negative; fp: false positive; fn: false negative; ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; gcs: glasgow coma scale; gaps: glasgow coma scale, age, and systolic blood pressure score; nts: new trauma score; rts: revised trauma score; mews: modified early warning score; news: national early warning score; wpss: worthing physiological scoring system; rems: rapid emergency medicine score; raps: rapid acute physiology score. figure 1: comparison of area under the receiver characteristics curve (auc) between assessed scoring systems in prediction of intensive care unit (icu) mortality. a) demonstration of the prediction rules with excellent performance (auc >0.90); b) demonstration of the prediction rules with good performance (auc between 0.70 and 0.90). ysis was used to estimate the sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (+lr), and negative likelihood ratio (lr) for each of gcs, nts, rts, wpss, raps, rems, mews, news, and gaps models. finally, the area under the curves (aucs) of all eight models were compared with gcs. the differences were considered statistically significant at p values < 0.05. analyses were performed using stata 14.0 software. the best cut-off point in each scoring system was determined using the youden index and similar studies (20, 24-26) . 3. results 3.1. baseline characteristics of studied cases a total of 200 trauma patients with the mean age of 43.53±19.84 years were included in the study (74% male). the percentage of the non-survivors among trauma patients in icu was 18.5% (n=37). the most common trauma mechanisms were motorcycle accidents (29.5%) and car accidents (21.5%). 29% of the patients had hypertension. the average length of stay in icu was 6.10±5.75 days. the significantly different vital signs between the two groups (survivors, non-survivors) were heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure (p<0.0001). the mean values of these vital signs in survivors were significantly higher than non-survivors. the percentage this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e25 figure 2: comparison of area under the receiver characteristics curve (auc) between assessed scoring systems in prediction of intensive care unit (icu) poor outcome (mortality or disability). a) demonstration of the prediction rules with excellent performance (auc >0.90); b) demonstration of the prediction rules with good performance (auc between 0.70 and 0.90). table 3: performance of physiologic scoring systems and glasgow coma scale in prediction of poor outcome in intensive care unit (icu) admitted trauma patients score cp tp tn fp fn sensitivity specificity ppv npv plr nlr gcs 9 66 124 1 9 88.0(78.4-94.4) 99.2(95.6-100) 98.5(92.0-100) 93.2(87.5-96.9) 110.00(15.6-776.2) 0.12(0.07-0.2) gaps 18 48 122 3 27 64(52.1-74.8) 97.6(93.1-99.5) 94.1(83.8-98.8) 81.9(74.7-87.7) 26.67(8.6-82.6) 0.37(0.3-0.5) nts 14 54 125 0 21 72.0(60.4-81.8) 100.0(97.1-100.0) 100.0(93.4-100.0) 85.6(78.9-90.9) 0 0.28(0.2-0.4) rts 7 62 118 7 13 82.7(72.2-90.4) 94.4(88.8-97.7) 89.9(80.2-95.8) 90.1(83.6-94.6) 14.76(7.1-30.5) 0.18(0.1-0.3) mews 4 66 77 48 9 88.0(78.4-94.4) 61.6(52.5-70.2) 57.9(48.3-67.1) 89.5(81.1-95.1) 2.29(1.8-2.9) 0.19(0.1-0.4) news 5 73 47 78 2 97.3(90.7-99.7) 37.6(29.1-46.7) 48.3(40.1-56.6) 95.9(86.0-99.5) 1.56(1.3-1.8) 0.07(0.02-0.3) wpss 4 51 82 43 24 68.0(56.2-78.3) 65.6(56.6-73.9) 54.3(43.7-64.6) 77.4(68.2-84.9) 1.98(1.5-2.6) 0.49(0.3-0.7) rems 6 48 111 14 27 64.0(52.1-74.8) 88.8(81.9-93.7) 77.4(65.0-87.1) 80.4(72.8-86.7) 5.71(3.4-9.6) 0.41(0.3-0.5) raps 4 51 104 21 24 68.0(56.2-78.3) 83.2(75.5-89.3) 70.8(58.9-81.0) 81.3(73.4-87.6) 4.05(2.6-6.1) 0.38(0.3-0.5) data are presented with 95% confidence interval. cp: cut off point; tp: true positive; tn: true negative; fp: false positive; fn: false negative; ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; gcs: glasgow coma scale; gaps: glasgow coma scale, age, and systolic blood pressure score; nts: new trauma score; rts: revised trauma score; mews: modified early warning score; news: national early warning score; wpss: worthing physiological scoring system; rems: rapid emergency medicine score; raps: rapid acute physiology score. of poor outcomes was 37.5% (n=75). the mean values of vital signs, including respiratory rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure, were significantly higher in the good outcome group compared to the poor outcome group (p<0.0001). the mean length of stay in icu in the poor outcome group was higher than the good outcome (p<0.0001) (table1). 3.2. accuracy of physiologic scoring systems in mortality prediction table 2 displays the roc curve analyses of the eight physiologic scoring systems and gcs. the sensitivity value of gcs was 100%. however, the sensitivity values of physiologic scoring systems, including nts, rts, wpss, raps, rems, mews, news, and gaps, were 97.3%, 100%, 83.8%, 86.5%, 83.8%, 94.6%, 97.3%, and 94.6%, respectively. also, the specificity value of gcs was 81.6%, and the specificity values of nts, rts, wpss, raps, rems, mews, news, and gaps were 89%, 80.4%, 61.3%, 75.5%, 81%, 51.5%, 29.4%, 90.2%, respectively (table 2). figure1 shows the auc values of physiologic scoring systems. the auc value for gcs was 0.98 (95% ci: 0.96 0.99). the auc values of nts, rts, wpss, raps, rems, mews, news, and gaps were 0.95 (95% ci: 0.92 0.98), 0.95 (95% ci: 0.92 0.98), 0.83 (95% ci: 0.76 0.90), 0.89 (95% ci: 0.84 0.94), 0.91 (95% ci: 0.86 0.95), 0.84 (95% ci: 0.78 0.90), 0.77 (95% ci: 0.69 0.85), and 0.97 (95% ci: 0.95 0.99), respectively. the auc of gcs was significantly higher than those this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khari et al. 6 of rts (p=0.005), wpss (p=0.0001), raps (p=0.0002), rems (p=0.002), mews (p=0.0001), and news (p=0.0001). however, the auc of gcs was not significantly different from nts (p=0.146) and gaps (p=0.513). 3.3. accuracy of physiologic scoring systems in poor outcome prediction table 3 represents the results of roc curve analysis for the eight physiologic scoring systems and glasgow coma scale. the sensitivity value of gcs was 88%. the sensitivity values of the eight physiologic scoring systems, including nts, rts, wpss, raps, rems, mews, news, and gaps, were 72%, 82.7%, 68%, 68%, 64%, 88%, 97.3%, and 64%, respectively. the specificity value for gcs was 99.2% and for nts, rts, wpss, raps, rems, mews, news, and gaps, values were 100%, 94.4%, 65.6%, 83.2%, 88.8%, 61.6%, 37.6%, and 97.6%, respectively (table3). figure 2 shows the auc values for all of the physiologic scoring systems. the auc value for gcs was 0.98 (95% ci: 0.97 1.00). the auc values of nts, rts, wpss, raps, rems, mews, news, and gaps, were 0.97 (95% ci: 0.95 0.99), 0.95 (95% ci: 0.92 0.98), 0.75 (95% ci: 0.68 0.81), 0.85 (95% ci: 0.80 0.90), 0.85 (95% ci: 0.80 0.91), 0.84 (95% ci: 0.79 0.89), 0.77 (95% ci: 0.71 0.84), and 0.97 (95% ci: 0.95 0.99), respectively. the auc for gcs was not significantly different from nts (p=0.182) and gaps (p=0.089), but the auc of gcs was considerably higher than those of rts (p=0.001), wpss (p<0.001), raps (p<0.001), rems (p<0.001), mews (p<0.001), and news (p<0.001). 4. discussion this study illustrated the performance of physiologic scoring systems including nts, rts, wpss, raps, rems, mews, news, gaps, and gcs in predicting traumatic patient mortality and poor outcomes in icu using the roc curve. accordingly, nts, rts, wpss, raps, rems, mews, news, and gaps performed well. however, compared to gcs, the scoring systems of rts, wpss, raps, rems, and mews had poorer performance and nts, and gaps were not significantly different from gcs. moreover, the sensitivity of gcs was higher than nts and gaps in predicting the mortality of patients. in this regard, different studies have been conducted, which had results consistent or inconsistent with the present study. in a cross-sectional study conducted on 125 traumatic brain injury patients admitted in icu, the efficacy of gcs and apache ii score were compared. the values of roc curve analysis for gcs (auc=0.81, ppv=69.2, sensitivity=61.4) and apache ii (auc=0.83, ppv=80.6, sensitivity=56.9) were acceptable, and they had no significant difference. however, for the initial evaluation, gcs was suggested because of its simplicity and quickness (5). in a diagnostic accuracy study with 1702 trauma patients in emergency departments of four hospitals, the performance of rts, raps, rems, and wpss was compared with gcs in predicting in-hospital deaths and poor outcomes. the results demonstrated that the auc value of gcs was not significantly different from that of raps, rems, and wpss. however, gcs performed significantly better than rts in prediction of in-hospital deaths. in addition, this conclusion was also proper for predicting poor outcomes in the emergency department such as mortality, vegetative state, and disability (14). another prospective observational study was conducted to evaluate the power of scoring systems including gcs, apache-ii, raps, and rems in predicting the need for mechanical ventilation in patients with drug overdose. the roc curve analysis showed that there were no significant differences between them. however, it seemed that the utilization of the combination of gcs >8 (npv=100%) and rems was beneficial in excluding patients without the need for ventilator support (27). a prospective diagnostic study was conducted to compare the accuracy of gcs and kts in prediciting in-hospital mortality. the auc for the gcs value on admission (0.91) and after 24 hours (0.96) was significantly higher than kts on admission (0.82) and 24 hours later (0.85). also, the gcs was more precise than kts in diagnosis of head injury patients (28). a diagnostic accuracy study on 1861 trauma patients assessed scoring systems including gap, mgap, iss, and gcs. the auc values of gap, mgap, iss, and gcs were 0.91 (sensitivity=72.99, specificity=95.52), 0.90 (sensitivity=81.04, specificity=87.70), 0.80 (sensitivity=89.10, specificity=61.11), and 0.88 (sensitivity=81.52, specificity=92.00), respectively. therefore, it seemed that both gap and mgap scoring systems could predict mortality (8). on the other hand, a retrospective study was performed to assess the accuracy of scoring systems such as gcs, iss, and rts in predicting outcomes in young children with traumatic injuries. the results demonstrated that the auc of iss in predicting mortality was higher than gcs and rts. also, worse trauma scores of iss, gcs, and rts correlated with more deaths (29). a retrospective study was conducted to determine the predictors of trauma patients’ deaths in icu. the auc values of scoring systems including gcs, iss, niss, rts, tris, risc ii, apache ii, saps ii, and sofa were 0.69, 0.82, 0.90, 0.74, 0.86, 0.88, 0.69, 0.67, and 0.69, respectively; so the niss and risc ii were more accurate in prediction of short-term mortality of patients with severe trauma (7). in a recent diagnostic accuracy study with 754 patients, the results indicated that the performance of rems was more precise than gcs, iss, and mews for prediction of in-hospital mortality rate of multiple trauma patients ≥ 24 hours after admission, and the auc value of rems (0.94) was significantly higher than gcs (0.85; p=0.035) (12). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e25 the differences between the results of this study and others may be related to considering different cut-off values, patient settings, and demographic characteristics. as an illustration, consider heydari et al.’s study with traumatic patients in the emergency department, in which 90% of patients had gcs≥13 (12). however, the present study was conducted in the icu and about half of the patients had gcs<13. in addition, heydari’s study is one of the few studies in which the sensitivity of gcs is found to be low (12), while most of the previous studies reported a high sensitivity for gcs (8, 14, 27, 28). 5. limitations a limitation of this study was the relative small sample size. a larger sample size and examining the patient at different time points provide more valuable and reliable results. convenience sampling was another shortcoming of the present diagnostic accuracy study. 6. conclusion according to this study, gcs has excellent accuracy in prediction of in-hospital outcome of trauma patients. since it is easy to use and calculate, gcs can be considered as the optimum predictive instrument in trauma patients. gcs is more practical and simple than physiological scoring systems, which are complex and time-consuming to measure. 7. declarations 7.1. acknowledgments this article is based on sorour khari’s master’s thesis and the study was conducted with the financial support of shahid beheshti university of medical sciences. 7.2. authors’ contributions study design: sk, mz, my; data gathering: sk; analysis and interpretation of results: my, mz drafting: sk; critically revised the paper: mz and my. all authors read and approved the final draft of manuscript and are responsible for all parts of study. 7.3. funding shahid beheshti university of medical sciences financially contributed to this study. 7.4. conflict of interest the authors declare that they have no conflict of interest. references 1. wärnberg gerdin l, khajanchi m, kumar v, roy n, saha ml, soni kd, et al. comparison of emergency department trauma triage performance of clinicians and clinical prediction models: a cohort study in india. bmj 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of different scores as predictors of mechanical ventilation in drug overdose patients. hum exp toxicol. 2017;36(6):539-46. 28. ariaka h, kiryabwire j, hussein s, ogwal a, nkonge e, oyania f. a comparison of the predictive value of the glasgow coma scale and the kampala trauma score for mortality and length of hospital stay in head injury patients at a tertiary hospital in uganda: a diagnostic prospective study. surg res pract. 2020;2020:1362741. 29. huang yt, huang yh. comparison of injury severity score, glasgow coma scale, and revised trauma score in predicting the mortality and prolonged icu stay of traumatic young children: a cross-sectional retrospective study. emerg med int. 2019;2019:5453624. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e69 rev i ew art i c l e accuracy of crest guideline in management of cellulitis in emergency department; a systematic review and metaanalysis hossein akhavan1, seyed reza habibzadeh2, fatemeh maleki3, mahdi foroughian2, sayyed reza ahmadi2, reza akhavan2, bita abbasi4, behzad shahi5∗, navid kalani6, naser hatami7, amir mangouri8, sheida jamalnia9 1.. department of pediatrics, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2.. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3.. department of emergency medicine, faculty of medicine, birjand university of medical sciences, birjand, iran. 4.. department of radiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 5.. department of emergency medicine, faculty of medicine, zahedan university of medical sciences, zahedan, iran. 6.. research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. 7.. student research committee, jahrom university of medical sciences, jahrom, iran. 8.. division of vascular surgery and endovascular therapy, department of general surgery, sina hospital, tehran university of medical sciences, tehran, iran. 9.. medical journalism department, shiraz university of medical sciences, shiraz, iran. received: september 2020; accepted: october 2021; published online: 3 november 2021 abstract: introduction: skin and soft tissue infections are important causes of outpatient visits to medical clinics or hospitals. this study aimed to review the literature for the accuracy of clinical resource efficiency support team (crest) guideline in management of cellulitis in emergency department. methods: studies that had evaluated cellulitis patients using the crest guideline were quarried in scopus, web of science, and pubmed database, from 2005 to the end of 2020. the quality of the studies was evaluated using scottish intercollegiate guideline network (sign) checklist for cohort studies. pooled area under the receiver operating characteristic curve (auroc) of crest guideline regarding the rate of hospital stay more than 24 hours, rate of revisit, and appropriateness of antimicrobial treatment in management of cellulitis in emergency department was evaluated. results: seven studies evaluating a total of 1640 adult cellulitis patients were finally entered to the study. in evaluation of the rate of the appropriate treatment versus over-treatment, the pooled auroc was estimated to be 0.38 (95% confidence interval (ci): 0.06 – 0.82), indicating low accuracy (auroc lower than 0.5) of guideline for antimicrobial choice. crest ii patients had a significantly lower odds ratio (or) of revisiting the emergency department, or=0.21 (95% ci: 0.009 – 0.47). pooled auroc value of 0.86 (ci95%: 0.84 – 0.89) showed accuracy of the crest classification in prediction of being hospitalized more or less than 24 hours. conclusion: crest classification shows good accuracy in determining the duration of hospitalization or observation in ed but it could lead to inevitable over/under treatment with empirical antimicrobial agents. keywords: cellulitis; emergency service, hospital; systematic review; skin diseases, bacterial; anti-bacterial agents cite this article as: akhavan h, habibzadeh s r, maleki f, foroughian m, ahmadi s r, akhavan r, abbasi b, shahi b, kalani n, hatami n, mangouri a s, jamalnia s. accuracy of crest guideline in management of cellulitis in emergency department; a systematic review and meta-analysis. arch acad emerg med. 2021; 9(1): e69. https://doi.org/10.22037/aaem.v9i1.1422. ∗corresponding author: behzad shahi; department of emergency medicine, faculty of medicine, zahedan university of medical sciences, zahedan, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akhavan et al. 2 1. introduction skin and soft tissue infections are important causes of outpatient visits to medical clinics or hospitals. these infections have a wide range of symptomatology and etiology that could even be life threatening in some cases (1). cellulitis is an acute infection of the skin and soft tissues. subcutaneous tissues show redness, pain, and swelling in the affected area. the most common etiology is staphylococcus aureus bacteria, followed by streptococcus pyogenes and many other gram-positive cocci and rarely some gram-negative germs (2). clinical evaluation of the severity of the infection is very important and decisive; however, the need for different diagnostic and therapeutic algorithms to guide physicians in reaching the right and appropriate decision has not been fully addressed (3). koerner et al. (2011) reviewed the recent attempts in classification of cellulitis cases and stated that primary classifications were assorting cases based on the site of the infection; while further studies suggested more comprehensive guidelines as well as the eron criteria (4). later, clinical resource efficiency support team (crest) was developed, based on the eron recommendations, addressed as eron/crest classification by some authors (5), with an easy method of classification for clinical application (6). but since systemic sepsis has not been fully considered in this guideline, some researchers have doubted its application in clinical practice (4). since no study has pooled the clinical outcomes of the crest application, this study aimed to review the literature on the accuracy of crest guideline in management of cellulitis in emergency department. 2. methods 2.1. study design and setting this study was performed in adherence to the guidelines of the preferential cases of the report for systematic review and meta-analysis (prisma) and is a systematic review and meta-analysis of the existing literature on the accuracy of crest guideline in treatment of cellulitis, published in peerreviewed journals. english language studies were quarried among all articles published from 2005 to the end of 2020, on the topic of cellulitis, since crest guideline was first established in 2005. studies which evaluated their study population using the crest guideline were searched in scopus, web of science, and pubmed databases by two researchers using the keywords of "crest ", "cellulitis" and "bacterial skin infection". only articles about cellulitis that contained iran. email: mr.shahi87@yahoo.com. tel: 00989151913501, orcid: http://orcid.org/0000-0001-9884-1542. the keywords of crest were included in initial search. 2.2. search strategy in pubmed, using the search strategy of [(crest or eron) and (cellulitis or bacterial skin infection)], 44 results were found. along with multiple scopus and web of science search results found using the same strategy, in the initial search, 135 potentially relevant articles were retrieved, 127 of which remained after removing the duplicate items. then, articles were selected based on the title and abstract, a list of abstracts was prepared. after hiding the details of the articles such as the author’s name, the name of the journal, etc., the full texts of the articles were given to 2 trained researchers to review the text of articles. each article was reviewed by 2 independent researchers and in case of rejection of the articles by both researchers, the reason was mentioned and in case of disagreement between them, the article was judged by a third person. 115 articles were excluded from the study due to irrelevance or not containing crest guideline in their methodology. finally, 12 articles met the inclusion criteria and entered the quality assessment process. 2.3. quality assessment a checklist of scottish intercollegiate guidelines network (sign) was used to evaluate the quality of these articles (7). seven articles had acceptable quality for being included in study. 2.4. statistical analysis a web-based calculator was used to determine area under the receiver operating characteristic (roc) curve (auroc) of the overall accuracy of crest in predicting the rate of hospital stay more than 24 hours (8). to combine the event rates or values of auroc with respect to the percentage or standard error of the values, the weighted average and the random effects were used in the meta-analysis due to the heterogeneity of the studies. the i2 index and the cochran test were used to examine the heterogeneity between the results. the egger’s test and funnel plot were used to examine the publication bias in the revman software version 5.4.1. in this meta-analysis, auroc of crest in predicting the studied variables was estimated and entered in a random effects model, due to high heterogeneity (i2=99%). 3. results 3.1. characteristics of included studies seven studies were finally entered into the quantitative synthesis in this meta-analysis, as shown in figure 1. six studies were prospective cohort studies and one was retrospective. two studies were conducted in iran, 3 studies in usa, and 2 in scotland. study setting was emergency department this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e69 (ed) in 4 studies; while 3 of the studies evaluated hospitalized patients (9-11). a total of 1640 patients were studied in our meta-analysis. all studies evaluated adult subjects (over 18 years old). we were not able to classify studies into subgroups for meta-analysis to see the possible differences between old and young adults. all studies had the same inclusion criterion, which was diagnosis of cellulitis. although evaluating distinct areas of cellulitis involvement, none of the studies included facial cellulitis. various outcomes were measured in different studies, so we could not include all studies ina quantitative synthesis for a particular outcome (table 1). 3.2. accuracy of crest guideline for hospitalization length results showed pooled auroc value of 0.86 (95%ci: 0.84 – 0.89) for crest guideline regarding hospitalization length based on the combination of results from 4 studies referenced in figure 2. but there was a high heterogeneity (i2=98%). no further subgroup analysis was possible to determine the source of heterogeneity. for empirical antimicrobial choices appropriateness of empirical antimicrobial choices was assessed in 3 studies (9-11) through evaluating biological cultures, as shown in table 3. results were summarized as undertreatment, overtreatment, or appropriate treatment in studies. as shown in figure 3, the pooled auroc of crest guideline for empirical antimicrobial choices was estimated to be 0.38, (95%ci: 0.06 – 0.82). for revisiting after being discharged as shown in figure 4, revisiting after being discharged from the emergency department was evaluated in studies by claeys (2014) and abiri. comparisons were only available for crest ii. crest ii patients had a significantly low odds ratio (or) of revisiting the ed, or=0.21 (95%ci: 0.009 – 0.47). publication bias to assess the publication bias, the funnel plot was visually inspected for asymmetry, as shown in figure 5. 4. discussion our study revealed that the pooled auroc for evaluating the rate of appropriate treatment versus overtreatment was 0.38 (95% ci: 0.06–0.82), indicating low accuracy (auroc less than 0.5) of crest guideline for antimicrobial choice. the odds of revisiting the emergency department were considerably lower in crest ii patients, with an or of 0.21 (95%ci: 0.009–0.47). the crest classification was shown to be accurate for being hospitalized for more than 24 hours with a pooled auroc of 0.86 (95%ci: 0.84 – 0.89). soft tissue infections are a common group of infections that are often mild to moderate in severity and are easily treatable. their etiological diagnosis is often difficult and unnecessary in most cases of cellulitis, where the patient has mild symptoms. our study was a systematic review of the studies that used crest guideline in management of cellulitis. there were few studies conducted in this area and only 7 studies were included. in our qualitative review. further assessment of study outcomes showed interesting findings in evaluation of empirical antimicrobial choices and hospitalization outcomes. laboratory investigations are suggested for crest ii-iv classes and most class i crest classified patients get outpatient care with first line antibiotic choice of oral flucloxacillin 500 mg per day. patients classified in class ii or higher classes may receive iv therapy (5, 6). although pooling the data of iv versus oral treatment was not possible in our study, duration of hospital stay in ed or observation units were evaluated in some of our included studies, which revealed that patients with higher crest classification had higher rates of staying in the hospital for more than 24 hours based on the auroc. staying in the hospital and observation units for more than 24 hours may also be showing the need for iv antibiotic therapy based on the findings of claeys et al(12, 13) and abiri et al. (14). but further laboratory investigations were not presented in all studies, as some of studies were evaluating outpatient cases, which had crest i and ii classes. our study showed that the pooled auroc for appropriateness of treatment was 0.38 (95%ci: -0.06 – 0.82), indicating no significant difference in appropriate or under/over treatment; thus, reconsiderations are needed for treatment of middle classes. the closeness of the definitions provided for classes i to iv may be the reason for uncertainty in the decisions for treatment of these cases. however, in our study, there was a large spatial heterogeneity in the included studies, which could suggest the role of differences in the pattern of antibiotic resistance of gram-positive bacteria as a heterogeneity factor. various studies conducted in iran show a high rate of antibiotic resistance in iran (15, 16), the pattern of which might be different from the united states and europe (17). 5. limitations there was a high amount of heterogeneity in some of our syntheses, but the small number of the included studies that had evaluated distinct types of study outcomes did not allow us to have a comprehensive review of the cause of the heterogeneity. since all included studies had similar inclusion criteria for their patient recruitment, various factors could have affected the results, causing heterogeneity. one of these factors that our study shows to modify the heterogeneity between the studies is the different study settings in the included articles. study setting was emergency department (ed) in 4 studies; while 3 studies evaluated hospitalized patients (9-11). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akhavan et al. 4 6. conclusion crest classification demonstrates good precision in deciding the duration of hospitalization or observation at the ed; however, the reliability of this guideline in antimicrobial agent choice or route of antibiotic administration remains unclear; and using these classifications had not been able to prevent over/undertreatment with antibiotics, which might be due to inadequate and vague description and potentially overlapping definition of each class. 7. declarations 7.1. acknowledgments we would like to thank the clinical research development unit of peymanieh educational and research and therapeutic center of jahrom university of medical sciences for providing facilities for this work. 7.2. conflict of interest statement the authors have declared that no competing interests exist. 7.3. funding/support this research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 7.4. authors’ contribution ha, sh and srh conceptualized the study questions and performed revisions. nk, nh, am and sj performed the searches. fm, mf and ra, ba, bsh conducted the statistical analyses. other authors provided the draft of the manuscript. 7.5. ethical considerations all ethical principles are considered in this article. references 1. bystritsky rj. cellulitis. infectious disease clinics. 2021;35(1):49-60. 2. norimatsu y, ohno y. predictors for readmission due to cellulitis among japanese patients. the journal of dermatology. 2021;48(5):681-4. 3. cranendonk d, lavrijsen a, prins j, wiersinga w. cellulitis: current insights into pathophysiology and clinical management. the netherlands journal of medicine. 2017;75(9):366-78. 4. koerner r, johnson ap. changes in the classification and management of skin and soft tissue infections. journal of antimicrobial chemotherapy. 2011;66(2):232-4. 5. fulton r, doherty l, gill d, harney a, harper c, jenkinson h. guidelines on the management of cellulitis in adults. northern ireland: crest. 2005. 6. vijayalakshmi b, ganapathy d. medical management of cellulitis. research journal of pharmacy and technology. 2016;9(11):2067-70. 7. miller j. the scottish intercollegiate guidelines network (sign). the british journal of diabetes & vascular disease. 2002;2(1):47-9. 8. eng j. roc analysis: web-based calculator for roc curves. baltimore: johns hopkins university. 2017 [updated 2014 march 19. available from: http://www.jrocfit.org. 9. marwick c, broomhall j, mccowan c, phillips g, gonzalez-mcquire s, akhras k, et al. severity assessment of skin and soft tissue infections: cohort study of management and outcomes for hospitalized patients. journal of antimicrobial chemotherapy. 2011;66(2):387-97. 10. marwick c, rae n, irvine n, davey p. prospective study of severity assessment and management of acute medical admissions with skin and soft tissue infection. journal of antimicrobial chemotherapy. 2012;67(4):1016-9. 11. hashem ng, hidayat l, berkowitz l, venugopalan v. management of skin and soft-tissue infections at a community teaching hospital using a severity-ofillness tool. journal of antimicrobial chemotherapy. 2016;71(11):3268-75. 12. claeys kc, lagnf am, patel tb, jacob mg, davis sl, rybak mj. acute bacterial skin and skin structure infections treated with intravenous antibiotics in the emergency department or observational unit: experience at the detroit medical center. infectious diseases and therapy. 2015;4(2):173-86. 13. claeys kc, zasowski ej, lagnf am, sabagha n, levine dp, davis sl, et al. development of a risk-scoring tool to determine appropriate level of care in acute bacterial skin and skin structure infections in an acute healthcare setting. infectious diseases and therapy. 2018;7(4):495-507. 14. abiri s, foroughian m, akbar h, mehramiz nj, hatami n, ameri aa, et al. the investigation of valid criteria for hospitalization and discharge in patients with limb cellulitis: a prospective cohort study. journal of emergency practice and trauma. 2020;6(2):55-8. 15. parastan r, kargar m, solhjoo k, kafilzadeh f. staphylococcus aureus biofilms: structures, antibiotic resistance, inhibition, and vaccines. gene reports. 2020;20:100739. 16. moravvej z, estaji f, askari e, solhjou k, naderi nasab m, saadat s. update on the global number of vancomycinresistant staphylococcus aureus (vrsa) strains. international journal of antimicrobial agents. 2013;42(4):370-1. 17. prestinaci f, pezzotti p, pantosti a. antimicrobial resistance: a global multifaceted phenomenon. pathogens and global health. 2015;109(7):309-18. 18. abbasi m, abiri s, ghanbari m-j, orimi mh. evaluation of crest guideline validity for diagnosis of non-facial this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e69 cellulites. journal of dermatologic research and therapy. 2016;1(2):05. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akhavan et al. 6 table 1: characteristic of studies included in the meta-analysis study design setting outcomes n inclusion criteria abbasi, 2016 (18) iran prospective cohort ed hospitalization less or more than 24 h revisit in 1 week 89 non-facial cellulitis abiri, 2020(14) iran prospective cohort ed hospitalization less or more than 24 h revisit in 1 week 100 limb cellulitis hashem, 2015(11) usa retrospective hospitalized appropriateness of empirical antimicrobial choices clinical response 369 patients admitted with cellulitis claeys, 2015 (12) usa retrospective cohort ed/or observation units 96-h ed revisit/hospitalization 308 adult cellulitis patients with less than 24 h of iv antibiotics without hospital admission claeys, 2018(13) usa observational cohort study ed or observation units area-under-thereceiver-operatingcharacteristic-curve (auroc) analysis of ed/ou versus inpatient 506 diagnosis of acute bacterial skin and skin structure infections marwick, 2011(9) scotland retrospective cohort hospitalized appropriateness of empirical antimicrobial choices 189 received antibiotic treatment for cellulitis in hospital marwick, 2012 (10) scotland cohort acute appropriateness of empirical antimicrobial choices 79 adult patients with cellulitis na: not addressed; ed: emergency department; ou: outpatient. table 2: quality of studies included in the meta-analysis based on the scottish intercollegiate guidelines network (sign) checklist study appropriate and clearly focused question predicting the outcome at the time of enrolment lost to follow up status addressed clearly defined outcomes a reliable method of exposure assessment evidence of outcome assessment exposure level or prognostic factor is assessed more than once the main potential confounders are identified and taken into account in the design and analysis have confidence intervals been provided? minimization of the risk of bias or confounding? clear evidence of an association between exposure and outcome? are the results of this study directly applicable to the patient group targeted in this guideline? abbasi, 2016 y y na y y n n n y n y y abiri, 2020 y y na y y n n n n y y y hashem, 2015 y y y y y y y y n y y y claeys, 2015 y y y y y y y y y y y y claeys, 2018 y y y y y y y y y y y y marwick, 2011 y y y y y n y n y y y y marwick, 2012 y y y y y y y y y y y y n: no; na: not addressed; y: yes. table 3: quality of antimicrobial treatment based on the clinical resource efficiency support team (crest) guideline treatment crest i crest ii crest iii crest iv marwick, 2012 appropriate 0(0) 4(4.6) 1(1.15) 18(20.69) under/over 19(21.84) 33(37.93) 3(3.45) 9(10.34) marwick, 2011 appropriate 57(33.53) 20(11.76) 10(5.88) 1(0.59) under/over 12(7.06) 36(21.18) 23(13.53) 11(6.47) hashem, 2015 appropriate 8(4) 65(32.5) 14(7) 3(1.5) under/over 60(30) 37(18.5) 10(5) 3(1.5) total appropriate 122(17.09) 113(15.83) 36(5.04) 41(5.74) under/over 122(17.09) 175(24.51) 62(8.68) 43(6.02) data are presented as number (%) if they were available in the studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e69 figure 1: prisma flow chart of study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akhavan et al. 8 figure 2: forest plot of clinical resource efficiency support team (crest) guideline’s accuracy for hospitalization length; less versus more than 24 hours (based on pooled area under the receiver operating characteristic (roc) curve). figure 3: forest plot of clinical resource efficiency support team (crest) guideline’s accuracy for appropriate antimicrobial treatment (based on pooled area under the receiver operating characteristic (roc) curve). figure 4: forest plot of clinical resource efficiency support team (crest) guideline’s accuracy for rate of revisit after being discharged (based on pooled area under the receiver operating characteristic (roc) curve). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e69 figure 5: funnel plot of the study to assess publication bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 134 emergency (2014); 2 (3): 134-137 original research quality of life in emergency medicine specialists of teaching hospitals afshin amini1, mohammad reza munesan1, hamid kariman1, ali arhami dolatabadi1, hamid reza hatamabadi1, 2*, ali shahrami1, majid shojaee1 1. department of emergency , imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran abstract introduction: quality of life (qol) of emergency medicine specialists can be effective in providing services to patients. the aim of the present study was evaluating the lifestyle of emergency medicine practitioners, understanding their problems, and addressing the solutions to enhance and improve their lifestyles, in teaching hospitals in iran. method: this descriptive cross-sectional study was conducted on emergency medicine physicians in 10 teaching hospitals of iran in 2011. emergency physicians with at least three years of experience, who interested in the study, were enrolled in the project. all participants filled out the consent form and qol questionnaires, and then underwent physical examinations and some medical laboratory tests. categorical variables were reported as percentages, while continuous variables expressed as means and standard deviations. p <0.05 was considered statistically significant. results: totally, 100 subjects participated in the study, of whom 48 were male. the mean and standard deviation of the physicians’ age were 38.7±5.1 years. 43% of physicians had an average qol, while 37% good. 96% of studied physicians had a good condition regarding habitual history, while 93% of them had a poor condition in performing screening tests. exercise program and personal health in individuals with normal bmi were correlated with higher levels of qol. bmi was higher in 40-50 years old subjects than youth. hypertension was present in five cases (5%), hypercholesterolemia in six (6%), hypertriglyceridemia in six (6%), increased ldl in four (4%), low hdl in four (4%), and impaired fbs in 4 (4%). conclusion: the findings showed that 63% of studied emergency physicians had an average level of qol and other ones good. the majority of physicians had undesirable situation regarding the performance of screening tests. key words: quality of life; emergency medicine; burnout, professional; physicians; job satisfaction cite this article as: amini a, munesan mr, kariman h, et al. quality of life in emergency medicine specialists of teaching hospitals. emergency. 2014;2(3):134-7. introduction:1 cademic emergency medicine the first time was created in nearly forty years ago, at university of ohio, in response to the increased public expectations for round-the-clock access to high quality and specialized medical care. the potentials of emergency medicine in improving the quality of care and increasing patient satisfaction on one hand, and its diverse and dynamic nature on the other hand have led to its huge leap in a short time. rapidly, it was one of the most popular majors in medicine, and was launched in more than forty other countries around the world. this major has propelled in iran in 2001 and currently there are more than 350 emergency medicine specialists and 200 emergency medicine residents in teaching hospitals across the country. evaluating the qol has attracted *corresponding author: hamid reza hatamabadi; department of emergency medicine, imam hossain hospital, shahid madani avenue, tehran, iran. tel/fax: +9821713432380; email: hhatamabadi@yahoo.com received: may 2014; accepted: july 2014 much attention as a scientific debate in recent years (1). researchers believe that evaluating the qol and improving it play an important role in healthy social and personal life (2, 3). individual's qol directly affects his/her physical and mental health. because of the especial working pattern of emergency medicine specialists (significantly greater difficulty, relatively undesirable standby, poor sleep patterns, etc.), the quality of their life has a critical effect on improving the quality of treatment process (4, 5). today, no study has yet been conducted in iran for examining the qol of emergency medicine specialists and just few studies were found in this field, globally. the aim of the present study was evaluating the lifestyle of emergency medicine practitioners, understanding their problems, and addressing the solutions to enhance and improve their lifestyles, in teaching hospitals in iran. methods: study design and setting a mailto:hhatamabadi@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 135 amini et al this descriptive cross-sectional study was conducted on emergency medicine physicians in 10 teaching hospitals of iran in 2011. emergency physicians with at least three years of experience, who interested in the study, were enrolled in the project. questions regarding qol, reported in the course of medline search in the previous study, were collected to develop a questionnaire using the research terms ‘emergency medicine specialist’, ‘lifestyle quality’, and ‘teaching hospital’. to validate the current questionnaire, a pilot study was done among forty residents at shahid beheshti university of medical sciences. the reliability of the questionnaire using cronbach's alpha coefficient was 0.85. face and content validity were confirmed by a methodologist, emergency medicine professors, and a group of people similar to the target population. all participants filled out the consent form and qol questionnaires, and then underwent physical examinations and some medical laboratory tests. the protocol of study was approved by the ethical committee of shahid beheshti university of medical sciences. qol questionnaire qol questionnaire was evaluated the participants regarding six aspects as follows: i: uncontrollable risk factors (the incidence of heart disease, hypertension, diabetes and stroke among immediate family members, and the incidence of chronic diseases and cancer among the physicians), ii: screening tests (colorectal screening, pap smears, mammography and prostate screening), iii: habitual history (smoking, caffeine and alcohol drinking), iv: exercise program (exercise, stretching, warm up and cool down moves), v: dietary habits (intake of food and water), vi: personal health (regular dental visits, eye care, environmental pollution and driving). using 30th and 70th percentiles as cut points, qol was categorized in poor (0 score), average (1 score) and good (2 score) based on likert scale. physical examination for blood pressure measurement, the subjects were asked to rest for 15 minutes and then it was measured in the right arm using a standard mercury sphygmomanometer. hypertension was defined as systolic blood pressure ≥ 140 mmhg, diastolic blood pressure ≥ 90. the weight and height were measured and body mass index (bmi) was calculated using the ratio of weight (kg) to height (m2). bmi index of 25-29.9 kg/m2 was considered as overweight and > 30 as obesity. laboratory tests fasting blood sugar level (fbs) was measured after eight hours fasting, while triglycerides (tg), cholesterol, low-density lipoprotein (ldl), and high-density lipoprotein (hdl) after 14 hours. hypercholesterolemia was defined as total cholesterol ≥ 200mg/dl, hypertriglyceridemia as tg ≥ 150, high ldl as ldl ≥ 130mg/dl and low hdl as hdl <40 mg / dl. statistical analysis categorical variables were reported as percentages, while continuous variables expressed as means and standard deviations. p <0.05 was considered statistically significant. the data were analyzed using spss ver. 20. results: of 100 participants, 48 were male and 52 female. the mean and standard deviation of physicians’ age was 38.7±5.1 years (range: 29-53). the mean of physician salaries was 1166.7±133.3 us dollars/month. qol in 63% of cases was average and in 37% good. none of the physicians had poor living conditions. table 1 shows the qol in different aspects of questionnaire based on likert scale. 96% of studied physicians had a good condition regarding habitual history, while 93% of them had a poor condition in performing screening tests. 53% of physicians had no regular exercise program and 23% exercised less than three days a week. exercise program and personal health in individuals with normal bmi were correlated with higher levels of qol (p=0.001). table 2 shows the result of laboratory and physical examination in the studied population. bmi was higher in 40-50 years old subjects than youth. table 3 shows the prevalence of cardiovascular risk factors in different age groups. as it can be seen, hypertension was present in five cases (5%), hypercholesterolemia in six (6%), hypertriglyceridemia in six (6%), increased ldl in four (4%), low hdl in four (4%), and impaired fbs in 4 (4%). discussion: the ed is the most active department in a hospital table 1: quality of life in different aspects of questionnaire based on likert scale  aspects mean ± sd poor (%) average (%) good (%) uncontrollable risk factors 1.55±0.56 3 (3) 39 (39) 58 (58) screening tests 0.07±0.26 93 (93) 7 (7) 0 habitual history 1.96±0.20 0 4 (4) 96 (96) exercise program 1.04±0.91 39 (39) 18 (18) 43 (43) dietary habits 1.42±0.50 0 58 (58) 42 (42) personal health 1.10±0.30 0 90 (90) 10 (10) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (3): 134-137 136 round-the-clock and fills with patients suffering from stress and illness. working in the ed requires enough interest, patience, wisdom, experience, and management. people may be exposed to many threatened risk factors because of their lifestyle, which some of them can be controlled, such as hypertension, high cholesterol and smoking while, others such as gender and family history cannot be managed. regarding the uncontrollable risk factors, it was found that fortunately none of the emergency physicians had cancer. age is one of the uncontrollable risk factors so that after the age of 55 the risk of cardiovascular diseases and stroke would double every 10-years. historical existence for any of such diseases in parents or family members is associated with the increased risk of them. however, the majority of physicians indicated that one or more of their family members in their 60s or even at earlier ages had diabetes, cardiovascular disease or stroke. controllable risk factors include hypertension, diabetes, smoking, alcohol drinking, obesity, and poor diet, which are preventable by proper diet, exercises, weight control, quitting smoking, and alcohol drinking (6-8). despite the importance of screening tests, 93% of physicians had poor conditions regarding performing of these tests. it cannot be due to their lack of knowledge, because physicians more than any other groups are aware from the importance of risk factors and the need for screening. the scores achieved by physicians in habitual habit aspect were the highest ones, as 96% had good scores. the reason for no drinking of alcohol by a majority of physicians included religious teachings on one hand and prohibition of the purchase and sale of alcoholic beverages in iran on the other hand. however, the consumption of products containing caffeine was common among physicians and only 5% did not use them. 87% of the physicians were nonsmokers and only 2% heavy smokers, which indicate an ideal situation in terms of tobacco abuse. based on the findings of previous studies conducted in canada, 82% of physicians committed tobacco abuse, 67% drank alcohol, and 32% were drug addicted (9). the findings of the present study suggested that iranian practitioners are healthier in this regard. in the fourth aspect, the findings indicated that 43% of physicians had good exercise programs and 39% poor. dietary habits of 58% of physicians was rated as average and for 43% of them, it was good. one of the issues related to the dietary habits of the physicians was the fact that only 39% of physicians drunk at least eight glasses of water daily while, other physicians were taking inadequate water. the last aspect assessed the personal health of the practitioners, 90% of physicians were rated as average, while 10% of them had good conditions. it seems that among emergency physicians in iran, long shifts, demanding and intense working have overshadowed all aspects of their lives, especially for female physicians; they abandon screening programs for follow-up of their health status, regular exercises, and even recreation or conduct these activities irregularly. many physicians have no good recreational activities and heavy workload with fatigue spoiled their qol. the average income of emergency physicians is reported to be 1166.7±133.3 us dollars monthly, which is a good income for living in iran. however, such a financial situation has not improved their qol. the study found no significant relationship between qol and gender, while in the previous studies, women had more job satisfaction than men but it decreased significantly in women who had children (10). the study also found no significant relationship between qol scores and age, while the previous studies showed that the older physicians had better qol than younger ones; qol were found to be decreased in another study for older specialists (10, 11). obviously, poor qol will result in occupational burnout. previous studies have shown that occupational burnout is a multifactorial issue influenced by individual characteristics, work and family stress (12, 13). night shifts, sleep disorders, work pressures, and personal health are the factors associated with occupational burnout. some issues in ed such as long working shifts, night shifts, and large number of patients are the factors that cause stress and depression in physicians. since their lower qol likely affects the quality of their services and commitment, this could also affect the public health, too (14, 15). in addition, as mentioned a large percentage of physicians' qol was rated as moderate; therefore, the relevant authorities should pay more attention to the qol of physicians and make some useful plans in order to improve the quality of their life. limitations table 2: the result of laboratory and physical examination of the subjects  factors values fasting blood sugar (mg/dl) 93.8±22 total cholesterol (mg/dl) 158±39.7 triglyceride (mg/dl) 136±17 high density lipoprotein (mg/dl) 53.2±13 low density lipoprotein (mg/dl) 103±23 body mass index (bmi) weight loss 0 normal weight 88 (88%) over weight 12 (12%) height (m) 163±9.6 weight(kg) 68±13 systolic blood pressure (mmhg) 118.6±14.3 diastolic blood pressure (mmhg) 77.4±9.5 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 137 amini et al this study had some limitations. many physicians were working in other cities than tehran, while the location of residence was not considered as an influencing factor for qol in the present study. the experiences and position were also not taken into account. it is suggested that a more comprehensive study should be conducted to include all of these questions for obtaining acceptable results in this regard conclusion: the findings showed that 63% of studied emergency physicians had an average level of qol and other ones good. the majority of physicians had undesirable situation regarding the performance of screening tests. acknowledgments: we would like to thank the head of ed, evaluation leaders, the head nurse of the department. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. sreenivas r, wiechmann w, anderson c, chakravarthy b, menchine m. 153: compassion satisfaction and fatigue in emergency physicians. ann emerg med. 2010;56(3):s51. 2. shanafelt td, boone s, tan l, et al. burnout and satisfaction with work-life balance among us physicians relative to the general us population. arch intern med. 2012;172(18):137785. 3. fortney l, luchterhand c, zakletskaia l, zgierska a, rakel d. abbreviated mindfulness intervention for job satisfaction, quality of life, and compassion in primary care clinicians: a pilot study. ann fam med. 2013;11(5):412-20. 4. bossola m, murri r, onder g, turriziani a, fantoni m, padua l. research physicians' knowledge of health-related quality of life and perception of its importance in daily clinical practice. health qual life outcomes. 2010;23(8):43. 5. west cp, shanafelt td, kolars jc. quality of life, burnout, educational debt, and medical knowledge among internal medicine residents. jama. 2011;306(9):952-60. 6. ishak w, nikravesh r, lederer s, perry r, ogunyemi d, bernstein c. burnout in medical students: a systematic review. clin teach. 2013;10(4):242-5. 7. paro hb, morales nm, silva ch, et al. health-related quality of life of medical students. med educ. 2010;44(3):227-35. 8. bright rp, krahn l. depression and suicide among physicians. curr psychiatry. 2011;10(4):16. 9. d'onofrio g, becker b, woolard rh. the impact of alcohol, tobacco, and other drug use and abuse in the emergency department. emerg med clin north am. 2006;24(4):925-67. 10. bellou v. organizational culture as a predictor of job satisfaction: the role of gender and age. career dev int. 2010;15(1):4-19. 11. boumans np, de jong ah, janssen sm. age-differences in work motivation and job satisfaction. the influence of age on the relationships between work characteristics and workers' outcomes. int j aging hum dev. 2011;73(4):331-50. 12. yoshida y, sandall j. occupational burnout and work factors in community and hospital midwives: a survey analysis. midwifery. 2013;29(8):921-6. 13. ahola k, hakanen j, perhoniemi r, mutanen p. relationship between burnout and depressive symptoms: a study using the person-centred approach. burnout res. 2014;1(1):29–37. 14. jenaro c, vega v, flores n, cruz m. quality of services and quality of life from service providers' perspectives: analysis with focus groups. j intellect disabil res. 2013;57(6):489-99. 15. atlantis e, goldney rd, eckert ka, taylor aw. trends in health-related quality of life and health service use associated with body mass index and comorbid major depression in south australia, 1998–2008. qual life res. 2012;21(10):1695-704. table 3: prevalence of cardiovascular disease risk factors  clinical situation age groups (n) <30 30-40 40-50 50-60 hypertension 0 0 4 1 hypercholesterolemia 0 1 4 1 hypertriglyceridemia 0 1 4 1 high ldl 0 1 4 1 low hdl 0 0 3 1 high blood sugar 0 0 3 1 emergency. 2018; 6 (1): e58 or i g i n a l re s e a rc h evaluation of airway management proficiency in prehospital emergency setting; a simulation study shahrzad ghiyasvandian1, afshin khazaei2∗, masoumeh zakerimoghadam3, rasoul salimi4, ali afshari5, abbas mogimbeigi6 1. department of medical surgical nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. intensive care and management nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 3. intensive care and management nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. emergency department, besat hospital, hamadan university of medical sciences, hamadan, iran. 5. intensive care and management nursing department. school of nursing and midwifery, hamadan university of medical sciences, hamadan, iran. 6. department of biostatistics and epidemiology, school of public health, hamadan university of medical sciences, hamadan, iran. received: july 2018; accepted: september 2018; published online: 2 october 2018 abstract: introduction: infrequency and low exposure to critically ill patients requiring airway management will lead to reduction in the skills and performance of the emergency medical technicians (emts) over time. the present study was conducted primarily aiming to evaluate airway management in stationary ambulance simulations and identify the factors affecting endotracheal intubation (eti) success rate. methods: this is a simulation study. the study population comprised of active emts in prehospital emergency bases in hamadan province. the participants were placed at the back of an ambulance to perform the airway management scenario, which had already been prepared. to investigate the factors affecting the success (≤3 attempts) or failure rate of intubation, both unadjusted and adjusted odds ratios (95% confidence intervals) for univariate and multivariate regressions were reported. results: 184 subjects with the mean age of 33.91+6.25 years and the median work experience of 8 years were studied (54.3% with a history of training in the past year). the median number of previous intubations performed by technicians in the last year was 7 times (iqr 4-9). the total success rate at ventilation, intubation and back-up airway were 50.67%, 53.29%, and 50.0%, respectively. out of the total 552 attempts for eti placement, 58.2% of the technicians were able to perform eti within 3 attempts. univariate analysis showed that age (or=1.06, p=0.022), previous number of etis (or=2.49, p<0.001), work experience (or=1.13, p<0.001), and previous eti training (or=1.85, p=0.041) were significantly associated with eti success rate. after adjustment, previous number of etis (or=2.66, p<0.001) was the most effective factor on eti success rate. conclusion: success rate in airway management, especially eti, is low. therefore, improvement in modifiable factors such as increasing the number of etis performed and gaining experience in the same conditions as pre-hospital emergency is necessary. keywords: airway management; endotracheal intubation; emergency medicine technicians © copyright (2018) shahid beheshti university of medical sciences cite this article as: ghiyasvandian sh, khazaei a, zakerimoghadam m, salimi r, afshari a, mogimbeigi a. evaluation of airway management proficiency in pre-hospital emergency setting; a simulation study. emergency. 2018; 6(1): e58. ∗corresponding author: khazaei afshin; intensive care and management nursing department, school of nursing and midwifery, nosrat st, tehran, iran. email: khazaei-a@razi.tums.ac.ir, tel: 00989183143075 1. introduction airway management in the out of hospital setting is associated with major challenges [1]. conditions such as limited access to advanced airway equipment, immobilized patients, confined spaces with dim light, shortage of personthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. ghiyasvandian et al. 2 nel, lack of back-up force and limited choice of alternative methods are substantial challenges of airway management in pre-hospital emergencies [2]. in the pre-hospital conditions, airway management involves a series of sequential steps and action to ensure airway openness to provide ventilation in the patient’s lungs [3]. inadequate performance at any step during airway management leads to irreparable injuries and complications in the patient [4, 5]. the most important stages of airway management include assessment, positioning, cleaning up the upper airway, adjunct oral airway insertion, supplemental oxygen administration, bag-valve mask ventilation (bmv ), placement of an endotracheal tube (ett), ett placement verification, stabilizing ett and applying alternative methods after unsuccessful endotracheal intubation (eti) [3]. the current training of emts is not enough to improve the patient’s airway management outcome [6]. furthermore, infrequency and low exposure to critically ill patients requiring airway management (especially eti) has added to the complexity of the situation and leads to poor skills and performance of the personnel over time [7]. the gold standard for advanced airway management is eti [8]. studies assessing eti success rate in an ambulance or a simulator are scarce. with the current overall out of hospital eti success rates ranging from 77 to 85% [9, 10] and a complication rate of 48 per 1000 intubations [10], the need to assure high levels of skill for performance and maintenance in a simulated environment is felt [10, 11]. consequently, accurate and continuous assessment and evaluation procedures for retention of airway management performance are critical to the improvement of patient outcomes [10, 11]. therefore, the primary objective of this study was evaluation of airway management in a simulated environment and the secondary purpose was identifying the factors affecting the success rate of eti in the emts. 2. methods 2.1. study design and setting this is a simulation study. the study was conducted in 115 emergency medical services in hamadan province, with 20 urban bases, 30 roadside bases and an air base (12). the present study was conducted from march 2018 to may 2018. emts participated in the study voluntarily and individual performance results were not reported to ems authorities. emts willing to participate in the study were requested to complete a brief demographic questionnaire and consent to video recording of their performance on the simulation practice. this study was approved by the ethics committee of hamadan university of medical sciences as research project no. 9611247613 and with the unique id no. ir.umsha.rec.1396.808. 2.2. participants the population of this study comprised emts in 115 emergency bases in hamadan province, which were recruited. in a study carried out by wang he et al. eti success rates were reported as 0.77% [9]. using this data and taking into account the relative error of 5% and 95% confidence interval, as well as applying the coefficient of the limited population (a total of 307 active emts, by formula ); we calculated that a sample size of 184 is required. the active emts who were present on a full-time basis in urban, road-side and air emergency and announced their oral and written consent were included in the study. non-active ems personnel were excluded from the study. the participants were placed in the back of an ambulance to perform the airway management scenario, which has already been prepared by experts. all stages of airway management by the emts were performed on a mannequin located in an ambulance resembling the pre-hospital emergency situation. 2.3. scenario 1 you have departed, along with your colleague, to a mission where a client’s consciousness is declined in a car accident. while examining, you notice that there is an incomprehensible voice in him. with painful stimuli, he opens his eyes and withdraws. on the left side of the temple, there is boggy contusion. it will take at least 20 minutes from the place of accident to the hospital. perform the required ventilation procedures based on the airway management protocol in the prehospital emergency in order a) through bag-valve mask, and b) then eti for the patient. 2.4. scenario 2 during the course, you notice that the patient’s et tube has been accidentally dislodged. you have attempted to intubate this patient twice since your first successful eti. you have noted that the airway was significantly edematous, full of secretions and you were unable to visualize the et tube pass through the vocal cords. pulse oximetry is also 80%. take the necessary measures in accordance with the airway management standard in the pre-hospital emergency. 2.5. data gathering the research instrument included a) demographic questionnaire of emt (including age, work experience, degree, employment status, intubation experience, previous training in airway management field); and b) airway management proficiency checklist (ampc) designed by david p. way et al. in 2017 [12]. this checklist consists of 3 standard performance scales for airway management, including ventilation, intubation and back-up airway, and a total of 37 psychomotor skills (8 skills for the ventilation scale, 17 skills for the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e58 flowchart 1: course of the airway management proficiency and the success rate of technicians in each of the stages of ventilation, intubation and back-up airway as well as outcome. bvm: bag vale mask. eti scale and 12 skills for the back-up airway scale) required for a comprehensive airway management. all 37 items were considered easily observable and rated by a qualified evaluator, and it’s had internal consistency in the three stages of ventilation (kr-20=0.95), intubation (kr-20=0.88) and backup airway (kr-20=0.82) (13). this checklist was filled out through direct observation made by two pre-hospital emergency training experts and under the supervision of an emergency medicine specialist. during the performance assessment, a trained supervisor read a standardized orientation (included an overview of the scenario, the available equipment, and a reminder to follow standard ems protocols for airway management) to the emts. all emts (184 cases) were evaluated individually with the two scenarios. also, all technicians, both those who were successful and those who failed in the first scenario were allowed to continue to the second scenario. based on the standard airway management guidelines [3], the maximum attempts (successful intubation) for eti was determined 3 times. if the technicians failed to perform eti in three attempts the result was recorded as failed intubation. also, if the technician had successful intubation during three attempts, it was recorded as successful intubation. the evaluators watched the recording and scored their performance using the 37 item checklist. the 37 items on the checklist were scored dichotomously either a “1” representing successful execution of the task, or a “0” representing a failed attempt or no attempt at all. after data collection, the status of technicians’ proficiency was determined at each stage of ventilation, intubation, back-up airway and sectors related to such stages. the evaluators used karl storz 8403zxk c-mac video laryngoscope, which allows observation and video recording of et tube placement, but emts were not shown the screen views during the simulation. the forward-only translation technique was used due to the lack of a persian version of the tool [13]. thus, after obtaining permission from the developer, the english version of the instrument was first translated individually into persian by two emergency medicine specialists. then the points of difference were investigated at a meeting with the presence of experts and pre-hospital emergency experts and specialists. finally, a single persian version of instrument was provided. for content and face validity, the checklist was given to 10 faculty members, emergency medicine specialist and emergency technicians, and their comments and suggestions were taken into consideration. tool reliability (in the mentioned three steps) was also confirmed via completion of 15 checklists by two emergency experts and determining the intra-rater reliability and calculating kappa coefficient (0.84%, 0.79%, and 0.91%). 2.6. statistical analysis continuous variables that were normally distributed were expressed as mean ± standard deviation (sd) while nonnormally distributed variables were expressed as median this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. ghiyasvandian et al. 4 (iqr). we dichotomized eti intervention into ≤3 attempts (successful) and >3 attempts (failure). ett correct positioning was determined by the placement of the tube within the trachea approximately 2-3 cm above the carina [17]. univariate logistic regression (unadjusted) was used to identify factors (continuous variables such as age, work experience, and previous number of etis and categorical variables such as previous training history [yes-no], degree [emergency medical technicians, nurse, operation room technician, anesthetist technician], and employment status [formal and informal]) associated with success or failure rate of eti. also, we used a multivariate logistic regression model for adjusting ors of continuous and categorical variables with eti success rate. to select covariates for the adjusted models used, the forward selection (wald) method was applied. ors and 95% cis were calculated. the selection of variables for the model was done according to factors known from the literature, which had previously assessed eti success rate [14-16]. all statistical analyses were performed using ibm spss statistics (v.17). p<0.05 was considered significant (two-tailed). 3. results 3.1. demographic information 184 emts took part in the study after being qualified for the inclusion criteria. the mean age of participants was 33.91+6.25 years and their median work experience was 8 years (iqr 5-13). the median number of intubations performed by technicians in the past year was 7 (iqr 7-9) times. 54.3% of the technicians reported a history of airway management training in the past year. 51.1% of the technicians had formal employment and some had academic degrees as emergency medical technicians (36.4%), nurses (27.2%), operation room technicians (20.1%) and anesthesiologists (16.3%). hosmer-lemeshow test showed good fit for the model (p = 0.48). 3.2. ventilation stage at the ventilation stage, the highest (65.2%) and the lowest (31.5%) success rates belonged to choosing correct adjunct airway size and checking pulse using thenar eminence technique, respectively. in the first section, 60.9% participants placed simple adjuncts prior to intubation to facilitate bag valve mask (bvm) performance. choosing the correct adjunct airway size was only observed in 60.9% of the technicians. 54.3% of the technicians succeeded in inserting adjunct airway with proper depth. the rate of bvm ventilation was also one of the evaluated sections. out of all the participants, less than 50% of the technicians ventilated the patient at the correct rate of 10–12 breaths per minute. in the next section, 42.9% (79 of 198) of the participants were observed for bvm technique for 30 seconds. using thenar eminence technique (e-c grip), in which downward pressure is applied with the thenar eminences while the four fingers of each hand pull the jaw upwards toward the mask, was only performed by 31.5% of the technicians. another significant section that was evaluated at the ventilation stage was taking precautions for cervical spine injuries (jaw-thrust maneuver, head-tilt/chin-lift maneuver), which only 48.9% of the technicians focused on this issue in our study while inserting airway and ventilating the patient with the bvm. eventually, the main outcome evaluated at this stage was ventilating the patient immediately (w/in 30 sec) with bvm and 53.8% of the technicians were able to do it. table 1 presents other results of the ventilation stage. 3.3. enodotercheal inutubation (eti) stage the complete item list for this process is listed in table 2. in the eti stage, the highest (89.7%) and the lowest (20.7%) success rates belonged to grasping laryngoscope with the left hand and checking end-tidal co2 after ett placement, respectively. in the first section of this stage, nearly three-quarters (71.2%) of the technician used straightto-cuff stylette curvature technique. 34.8% of the technicians passed ett through cords with limited or no impingement. also, 61.4% maintained their view correctly until ett stopped advancing. less than 50% of the technicians provided the correct position for the patient’s head before insertion of the laryngoscope into the mouth. passing tube through cords (laryngoscope in mouth to tracheal placement) in ≥20 seconds was only perfomed by 34.8% of the technicians. investigation of end-tidal co2 is another significant section of this stage which is considered one of the noninvasive methods for determining the correct position of the eti. only 20.7% of the emts checked end-tidal co2 after ett placement. in our study, nearly half of the emts (49.2%) succeeded in placing the tube at the appropriate depth in the trachea. passing the tube through cords (laryngoscope in mouth to tracheal placement) in less than 20 seconds was also another important section of the intubation stage that only 22.8% of the technicians were able to perform this skill. one of the maneuvers that facilitate passing of the tube into the trachea is the use of pressure on the epiglottis to better see the trachea when inserting the tube [18]. in this section, only 39.1% of the technicians requested the assistant to apply pressure on the patient’s epiglottis. finally, the technicians lacked enough skill to evaluate the main consequence of this stage, which was placement eti with one attempt, and only 12.5% of the technicians were able to show this skill. table 2 presents the other parts of the intubation stage. 3.4. back-up airway stage at the backup airway placement stage, the highest (93.5%) and the lowest (16.8%) success rates belonged to immedithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e58 table 1: frequency of paramedics who correctly performed tasks related to airway (n = 184) description frequency (%) inserts oropharyngeal (adjunct) airway 112 (60.9) chooses correct adjunct airway size 112 (65.2) inserts adjunct airway to proper depth 100 (54.3) ventilates patient at rate of 10–12/min 87 (47.3) observes bvm technique for 30 seconds* 79 (42.9) orients mask correctly 106 (57.6) uses thenar eminence technique (e-c grip) 58 (31.5) maintains c-spine precautions during bvm 90 (48.9) ventilates patient immediately (w/in 30 sec) with bvm 99 (53.8) * evaluates volumes (visible chest rise); endotracheal tube (ett); c-spine: cervical spine; bvm: bage valve mask. ately disconnecting syringe after inflating cuff and checking end-tidal co2 after backup airway placement, respectively. the need for backup airway in the patients was only recognized by 36.4% of technicians in the designed scenario (scenario 2). however, in this scenario, technicians who did not recognize the need for a back-up airway in the patient were asked to complete the back-up airway process based on the protocol. identifying an appropriate backup airway device was only done by 58.7% of the technicians. only 36.4% of the technician confirmed proper placement by auscultation bilaterally over each lung-backup airway. also, approximately 50% of technicians succeeded in inserting laryngeal mask airway in one step as the main outcome of this stage. table 3 indicates other results in this section. logistic regression results also showed that implementation of previous intubation in the last 12 months (or=2.66) and work experience (or=1.52) in the presence of other variables (such as dgree, previous eti training, employment status), are the most impactful factors that can increase the chance of successful intubation. in the unadjusted univariate analysis, number of previous etis (or=2.49: ci 95% [1.98-3.59], p<0.001), age (or=1.06: ci 95% [1.00-1.11], p=0.022), work experience (or=1.13: ci 95% [1.06-.1.2], p<0.001) and previous eti training (or=1.85: ci 95% [1.02-3.36], p=0.041) were significantly associated with eti success rate. also, factors such as degree (emt: or=0.92 cl 95% [0.38-2.23], p = 0.868, nurse: or=0.92 ci 95% [0.36-2.31], p=0.860, operating room technician: or=0.87 ci 95% [0.32-2.32], p=0.869), employment status (or=0.74: ci 95% [0.41-1.33], p=0.319) were not significantly associated with eti success rate. when adjusted for previous number of eti, age, degree, and previous eti training and employment status, only number of previous etis (or=2.70: ci 95% [1.98-1.38], p<0.001) and work experience (or=1.52: ci 95% [1.15-2.01], p=0.003) correlated with eti success rate (sensitivity [85.7], specificity [89.7]). age (or=0.78: ci 95% [0.62-0.98], p=0.037) was a negative predictive factors with eti success rate. hosmer–lemeshow test also showed goodness of fit for the model (p=0.496). 4. discussion the total success rate in the three stages of ventilation, intubation and airway back-up were 50.67%, 53.29%, and 50.0%, respectively. out of the total 552 attempts for eti placement, 58.2% of the technicians were able to perform eti in ≤3 attempts and 43.9% of technicians took more than 3 attempts to perform this skill. also, 12.5% (23 of 184) of the emts were successful at eti in their first attempt, which increased to 17.9% and 27.7% in the 2nd and 3rd attempts, respectively. these results are quite disappointing compared to other studies performed in this area. in the panchal study, the first pass eti success rate was 55.6% [19]. the study by griesdale et al. also indicated that 94% of the experienced emts succeed in eti within 2 attempts and only 6.6% of intubation cases by technicians required three attempts [20]. the poor results of our study at the eti stage are highlighted by the fact that re-intubation on the real patients will lead to complications, such as hypoxemia, aspiration, bradycardia and cardiac arrest [21]. passing the tube through cords (laryngoscope in mouth to tracheal placement) in less than 20 seconds was also another important section of the intubation stage, in which only 22.8% of the technicians succeeded. there is no doubt regarding the significance of the mentioned step (rapid intubation) because based on the results of previous studies, rapid intubation in cardiopulmonary resuscitation can lead to favorable outcomes, including improved neurological status and increased survival of patients [22, 23]. also, inserting the tube with the appropriate depth is another important skill for eti, which is crucial because ignoring this issue leads to serious complications that may even lead to death in some cases [24, 25]. unfortunately, 42.9% of the emts paid attention to this issue. the initial approach to airway management in the pre-hospital emergency is bag-valve mask ventilation (bmv ) [26, 27], which is more vital than intubation procedures in some special circumstances (e.g. severe airway trauma, lack of experience in personnel, children, etc.) [28, 29]. hansen et al. also indicated in their study that for airway management in chilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. ghiyasvandian et al. 6 table 2: frequency of paramedics who correctly performed tasks related to endotracheal intubation (n = 184) description frequency (%) uses straight-to-cuff stylette curvature technique 131 (71.2) checks equipment for cuff leaks 55 (29.9) positions head properly 85 (46.2) grasps laryngoscope with left hand 165 (89.7) elevates mandible from 45–90 degrees w/laryngoscope 122 (66.3) flips up epiglottis to expose larynx 72 (39.1) inserts laryngoscope to appropriate depth 79 (42.9) moves blade tip smoothly without shaking or jerking 83 (45.1) maintains view until ett has stopped advancing 113 (61.4) passes ett through cords with limited or no impingement 64 (34.8) passes tube through cords in ≥ 20 seconds * 42 (22.8) disconnects syringe immediately after inflating cuff of ett 149 (81.0) listens over each lung 124 (67.4) checks end-tidal co2after ett placement 38 (20.7) checks pulse oximeter-after ett placement 63 (34.2) maintains control over ett placement 124 (67.4) secures et tube (with device) 158 (85.9) successfully intubates within 1 attempt 21 (12.5) ∗ laryngoscope in mouth to tracheal placement; et: endotracheal; ett: endotracheal tube. table 3: frequency of paramedics who correctly performed tasks related to backup airway (n = 184) description frequency (%) recognizes need for backup airway 67 (36.4) identifies an appropriate backup airway device 108 (58.7) checks equipment for cuff leaks 78 (42.4) immediately inflates cuff, prior to ventilation 163 (88.6) immediately disconnects syringe after inflating cuff 172 (93.5) confirms proper placement by auscultation* 67 (36.4) checks end-tidal co2 -after backup airway placement 31 (16.8) checks pulse oximeter-after backup airway placement 82 (44.6) appropriately positions equipment needed for backup airway 53 (28.8) maintains control over backup airway after placement 68 (37.0) secures backup airway device 118 (64.1) introduces backup airway and advances to proper depth 97 (52.7) successfully places backup airway within 1 attempt 90 (48.9) * bilaterally over each lung-backup airway. dren, bvm would lead to a higher survival rate for the patient in hospital compared to eti [30]. ventilation with bvm seems a simple technique, though its proper implementation is difficult in practice, especially when the technicians lack enough experience in this area. in our study, the success rate of ventilating the patient with the rate of 10–12/min was low and this problem is more pronounced when knowing the increase (hyperventilate) or reduction (hypoventilation) in ventilation is determining the patient’s final condition [31]. unfortunately, in the backup airway stage also only 36.4% of the technicians recognized need for backup airway. when emts confronted with failed eti, using an alternative airway such as combitube and laryngeal mask airway (lma) would be an effective and efficient way to keep the airway open and ventilate [32]. in the backup airway (16.8%) and intubation stage (20.7%), the lowest success rate belonged to checking end-tidal co2 after backup airway placement. this method along with auscultation of bilateral breath sounds is the gold standard for determining the correct position of the et tube in the pre-hospital setting [33], which has 100% sensitivity and specificity in pre-hospital conditions [34]. therefore, the american heart association (aha) recommends it for all intubations [35]. also, in the present study, the success rate of backup-airway insertion in difficult conditions (scenario 2) was higher than the eti (48.6% vs 18.6%). this result confirms the ease of using laryngeal mask airway compared to eti, which is consistent with the results of other studies in this area [36, 37]. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e58 regression test also showed that one of the factors that can affect the success rate of airway management is to perform this skill in situations similar to the pre-hospital environment. after adjustment for confounding variables, gaining experience through implementation of intubation was found to be effective in enhancing the skills of eti, so that with performing one previous intubation, success rate increased by 2.66%. this result is confirmed by other studies, because achieving a 90% success rate in eti requires a history of performing 50–150 intervention [38, 39]. also, unadjusted regression shows that previous training in intubation was also significantly associated with eti success rate but when it’s adjusted for other factors such as previous number of intubations, this relationship was no longer significant. these results confirm that training methods such as theory-based teaching, lecture-based teaching as well as writing exam, cannot guarantee the success of technicians in managing practical skills. finally, the results of this study should be cautiously interpreted in the field. a major limitation of this study was the possibility of selection bias because technicians who have improved airway management proficiency may have been included in the study. also, since this study was conducted at a stationary ambulance and did not have the limitations of conducting airway management in a moving ambulance, its results may not reflect the current performance of the technicians in this study. in addition, the use of simulation in addition to the bias created by the ambulance personnel’s awareness result in the personnel not having environmental stresses such as encountering the scene of an accident, the risk of a patient’s life, the pressure of personnel to control and stabilize the patient’s condition and the existence of complications such as secretion, hemorrhage, vomiting in airway interventions and these factors may lead to false results of eti. in conclusion, the results of this study may be different from real situations. 5. limitation this type of study is not possible in the field due to acuity of illness, inability to accurately observe the details, and infrequency of airway management. the obtained results in this study should be carefully interpreted and used due to the lack of devices for determining the proper placement of eti such as end-tidal co2 detection device, as well as alternative back-up airway equipment such as combitube and laryngeal mask airway in the pre-hospital emergency service of hamadan province. 6. conclusion success rate in airway management, especially eti, is low. therefore, improvement in modifiable factors such as increasing the number of etis performed and gaining experience in the same conditions as pre-hospital emergency is necessary. 7. appendix 7.1. acknowledgements the authors are grateful to vice-chancellor of research and technology in hamadan university of medical sciences for supporting this study with a grant under the project number 9611247613. 7.2. author contribution khazaei afshin, ghiyasvandian sharzad and zakerimoghadam designed the simulation study. khazaei afshin, salimi rasoul and afshari ali carried out the implementation and supervised the work. mogimbeigi abbas analyzed the data and aided in interpreting the results. finally, khazaei afshin and ghiyasvandian sharzad discussed the results and contributed to the final manuscript. authors’ orcids ghiyasvandian shahrzad: 0000-0003-0137-5499 khazaei afshin: 0000-0002-8063-3419 zakerimoghadam masoumeh: 0000-0002-9762-1887 salimi rasoul: 0000-0002-6463-6046 afshari ali: 0000-0002-4579-5869 mogimbeigi abbas: 0000-0002-3803-3663 7.3. funding/support this work was supported by the vice-chancellor of research and technology, hamadan university of medical sciences under grant number 9611247613. 7.4. conflict of interest the authors report no conflict of interest. the authors alone are responsible for the content and writing of the paper. references 1. prekker, m.e., h. kwok, j. shin, d. carlbom, a. grabinsky, and t.d. rea, the process of prehospital airway management: challenges and solutions during paramedic endotracheal intubation. critical care medicine, 2014. 42(6): p. 1372-1378. 2. byars, d., b. lo, and j. yates, evaluation of paramedic utilization of the intubating laryngeal mask airway in highfidelity simulated critical care scenarios. prehosp disaster med, 2013. 28(6): p. 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poelaert, [manual skills in anaesthesiology]. anaesthesist, 2003. 52(6): p. 527-34. 40. burton, j.h., m.r. baumann, t. maoz, j.r. bradshaw, and j.e. lebrun, endotracheal intubation in a rural ems state: procedure utilization and impact of skills maintenance guidelines. prehosp emerg care, 2003. 7(3): p. 352-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e31 https://doi.org/10.22037/aaem.v9i1.1052 or i g i n a l re s e a rc h heart score in predicting one-month major adverse cardiac events in patients with acute chest pain; a diagnostic accuracy study hossein alimohammadi1∗, majid shojaee1, mohammad reza sohrabi2, saman salahi1 1. emergency department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. received: january 2021; accepted: february 2021; published online: 27 march 2021 abstract: introduction: screening of high-risk patients and accelerating their therapeutic procedures can reduce the burden of acute coronary syndrome (acs). this study aimed to evaluate the accuracy of heart score in predicting the risk of one-month major adverse cardiac events (mace) in these patients. methods: in this prospective cross-sectional study, the accuracy of heart score in patients over 18 years old who presented to emergency department following acute chest pain, was evaluated during a 21-month period. each patient was followed up regarding the incidence of mace for one month via phone call and the hospital’s integrated health information system. results: 240 cases with the mean age of 60.50 ± 16.07 years were studied (56.3% male). mace was observed in 77 (32.1%) cases. the most common mace was percutaneous coronary artery revascularization (pcar) (12.9%). the mean heart score of studied cases was 4.74 ± 2.12. the mean score of cases with mace was significantly higher than others (6.25 ± 1.97 versus 4.03 ± 1.79; p < 0.0001). based on this score, the risk of mace was high in 34 (14.2%), moderate in 118 (49.2%), and low in 88 (36.7%) cases. the incidence of one-month mace was 85.3% in high-risk cases, 35.6% in moderate one, and 6.8% in low-risk cases based on heart score. the area under the roc curve of heart score in predicting the risk of mace was 0.796 (95% ci: 0.736 – 0.856). the best cut off point of heart score in this regard was calculated as 4.5. the sensitivity and specificity of this score in 4.5 cut off were 83.11% (95% ci: 72.49 – 90.35) and 66.25% (95% ci: 58.38 – 73.35), respectively. conclusion: based on the findings of the present study the mean heart score of acs patients with one-month mace was significantly higher than others and the incidence of mace in high-risk patients was significantly higher. but the overall accuracy of score in predicting one-month mace in acs patients was in moderate range. keywords: chest pain; heart diseases; heart disease risk factors; acute coronary syndrome; emergency service, hospital cite this article as: alimohammadi h, shojaee m, sohrabi m r, salahi s. heart score in predicting one-month major adverse cardiac events in patients with acute chest pain; a diagnostic accuracy study. arch acad emerg med. 2021; 9(1): e31. 1. introduction cardiovascular diseases are currently the most common cause of morbidity and mortality among men and women of all races and ages worldwide, the most prevalent of which is coronary artery disease (cad) (1-3). according to the american heart association, these diseases are the cause of one in three deaths in the united states and an average of about 2,200 americans die from these diseases each day (4). based ∗corresponding author: saman salahi; emergency medicine department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. email: saman.salahi@gmail.com, tel: (+98)-21-7755-8081. fax: (+98)-21-7755-7069, orcid: https://orcid.org/0000-0003-4364-9945. on research done on this matter, the rate of heart disease in iran has increased by 20 to 25 percent in recent years (5). human error is considered a major risk factor in diagnosing these accidents (6) and preventing these errors is one of the most important and common challenges in the healthcare system (7). also, chest pain is one of the most common causes of emergency room visits, which may be due to lifethreatening conditions such as serious coronary artery disease (8). this disease is one of the most prevalent, costly, and debilitating diseases. hence, identifying the factors that can help in reaching a rapid diagnosis is of great importance (9). correct and rapid detection of serious coronary artery disease is crucial as undiagnosed cases had a high mortality rate and constituted the majority of medical malpractice lawsuits this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. alimohammadi and et. al 2 in the united states in 2016 (10). the heart score is a simple scoring tool for determining the risk of ischemic events in patients with acute chest pain, who presented to the emergency department, which is designed to differentiate the group of patients who can be quickly discharged from the emergency department (11) from those who need to be hospitalized for further investigations or treatments. rapid, accurate, and reliable results enable the physician to discharge low-risk patients with high confidence and without additional tests, and to quickly identify high-risk patients for future invasive measurements and reduce the probability of error (12, 13). considering that evaluation and monitoring of patients referring to the hospital with chest pain is very important and costly, scoring systems such as heart are designed to prevent unnecessary hospitalization of patients and reduce inpatient expenses at the time of admission, which results in reduced stress and anxiety as well. the present study aimed to evaluate the accuracy of heart score in predicting the risk of onemonth major adverse cardiac events (mace) in patients presenting to emergency department following acute chest pain. 2. methods 2.1. study design and setting in the present cross-sectional prospective study, the accuracy of heart score in predicting the risk of one-month mace in patients who presented to the emergency department (ed) of imam hossein hospital in tehran, iran, from may 2018 to march 2020, complaining of acute chest pain, was assessed. the researchers were committed to following the ethical principles of clinical research and all the patient data were kept confidential. methodology of the study was approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.msp.rec.1397.250). 2.2. participants the required sample size for this study was calculated to be 225 cases, using the cochran formula. of the 406 patients over 18 years of age who arrived at the emergency department of imam hossein hospital in tehran complaining of chest pain during the above-mentioned time period, 240 cases who had sufficient follow-up data were entered in the study via census sampling method. cases with incomplete medical profile, those who died due to any non-cardiac reason, and patients who refused to cooperate, were excluded. 2.3. data gathering demographic data (age, sex), history of present illness, electrocardiographic (ecg) findings, risk factors of coronary artery disease (hypertension, hypercholesterolemia, diabetes mellitus, previous cardiac disease, smoking, obesity, and atherosclerosis), and initial serum troponin level, which figure 1: area under the receiver operating characteristics (roc) curve of heart score in predicting major adverse cardiac events in patients with acute coronary syndrome. are all noted in heart score, were gathered using a predesigned checklist. this information was collected by a general physician or an emergency medicine resident at the time of the patient’s first visit to the ed under the direct supervision of emergency medicine specialists. mace was defined as: acute myocardial infarction (ami), death due to acute cardiac event, coronary artery bypass graft (cabg) surgery, percutaneous coronary artery revascularization (pcar). these data were extracted and gathered by a senior emergency medicine resident through phone calls and reviewing the hospital health information system (his). 2.4. calculating patients’ scores in this scoring scale, heart is an abbreviation, which stands for history, ecg, age, risk factors, and troponin level; each one gets a score of 0, 1, or 2 (14). total scores between 0-3 define low-risk cases, scores 4-6 indicate moderate risk, and scores 7-10 are indicative of high-risk cases. 2.5. statistical analysis convenience sampling was used for this study. after entering data to a designed excel sheet, they were analyzed using spss 21 statistical software. to report the findings, frequency and percentage, or the descriptive-mean statistics were used. chi-square and t-test were also used for analysis of data. the area under the receiver operating characteristic (roc) curve of heart score was used for calculating the accuracy and the best cut-off point of this score in predicting one-month mace. screening performance characteristics of heart score at the best cut-off point was calculated and reported with 95% confidence interval (ci). level of significance was considered to be 0.05. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e31 table 1: baseline characteristics of studied cases variable number (%) sex male 135 (56.3) female 105 (43.8) age (years) <45 42 (17.5) 45-65 110 (45.8) ≥65 88 (36.7) suspicion for acs low 12 (5.0) moderate 80 (33.3) high 148 (61.7) electrocardiography findings normal 121 (50.4) non-specific repolarization disturbance 75 (31.3) significant st depression 44 (18.3) number of risk factors* 0 79 (32.9) 1-2 108 (45.0) ≥3 53 (22.1) initial troponin level (ng/ml) <0.05 158 (65.8) 0.05 0.12 62 (25.8) >0.12 19 (7.9) adverse cardiac events percutaneous coronary artery revascularization 31 (12.9) acute myocardial infarction 26 (10.8) coronary artery bypass graft surgery 9 (3.8) death due to acute cardiac complication 11 (4.6) no acute cardiac complication 142 (59.2) * diabetes mellitus, smoking, hypertension, hypercholesterolemia, obesity, atherosclerosis, family history of coronary artery disease. acs: acute coronary syndrome. table 2: screening performance characteristics of heart score in predicting major adverse cardiac event in patients with acute coronary syndrome at 4.5 cut-off point character value (95% ci) sensitivity 83.11 (72.49 – 90.35) specificity 66.25 (58.38 – 73.35) positive predictive value 53.78 (44.43 – 62.88) negative predictive value 89.25 (81.99 – 93.92) positive likelihood ratio 1.16 (.90 – 1.50) negative likelihood ratio 0.12 (0.07 – 0.20) ci: confidence interval. 3. results 3.1. baseline characteristics of cases throughout the 22 months that this study was performed, a total of 406 patients presented the emergency department complaining of acute chest pain and were evaluated. 166 (40.8%) cases were excluded from the study due to missing data or their unwillingness to participate. the remaining 240 qualified cases were entered to the study (56.3% male). the mean age of patients was 60.50 ± 16.07 (22 – 95) years. table 1 shows the baseline characteristics of studied cases. mace was observed in 77 (32.1%) cases. the most common mace was pcar (12.9%). 3.2. accuracy of heart score the mean heart score of studied cases was 4.74 ± 2.12. the mean score of cases with mace was significantly higher than others (6.25 ± 1.97 versus 4.03 ± 1.79; p < 0.0001). based on this score, the risk of mace was high in 34 (14.2%), moderate in 118 (49.2%), and low in 88 (36.7%) cases. there was a significant correlation between the heart score’s predicted risk of mace and experience of mace (p < 0.0001). the incidence of one-month mace was 85.3% in high-risk cases, 35.6% in moderate ones, and 6.8% in low-risk cases based on heart score. the area under the roc curve of heart score in predicting the risk of mace was 0.796 (95% ci: 0.736 – 0.856). the best cut-off point for the score in this regard was calculated as 4.5 (figure 1). the screening performance characteristics of this score in 4.5 cut-off point is presented in table 2. the sensitivity and specificity of the score in 4.5 cut-off were 83.11% (95% ci: 72.49 – 90.35) and 66.25% (95% ci: 58.38 – 73.35), respectively. 4. discussion based on the findings of the present study the mean heart score of acs patients with one-month mace was significantly higher that others and the incidence of mace in highrisk patients was significantly higher. but the overall accuracy of this score in predicting one-month mace in acs patients was in moderate range with 83.11% sensitivity and 66.25% specificity. heart score is a tool for facilitating making diagnostic and therapeutic decisions regarding patients with chest pain who present to the emergency department, without the use of radiation or invasive methods. it seems to be an easy, rapid, and reliable predictive tool for evaluating patients with chest pain, which can be used to triage these patients in the ed and also prevent further hospitalization for costly and timeconsuming diagnostic work-ups in suspected but low-risk patients. the results of the present study showed that the majority of patients with chest pain were categorized in the moderaterisk group, which is consistent with the study by six et al. (15), while the study by melki et al. stated that 60.2% of patients were categorized as a low-risk group (16); and also the study by gharaee et al., which stated that the majority of patients with chest pain were in the low-risk group (17). the average heart score was 4.03 in the group without this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. alimohammadi and et. al 4 mace, and 6.25 in the group of patients with mace, which supports the study by backus et al. that reported the average scores of 3.96 and 6.54 in the group with no cardiac events and the group with mace, respectively (18). the most common mace in patients included percutaneous coronary artery revascularization, myocardial infarction, coronary artery bypass graft surgery, and death due to acute cardiac complications, respectively; which is consistent with the study by backus et al. in 2013 (18). more than half of all patients who referred with chest pain showed no severe cardiac complication after a month, which is consistent with the results of backus et al., indicating that 83% of patients showed no cardiac complications (18). high-risk patients based on the heart score had the highest incidence of adverse cardiac events, which was consistent with the study by backus et al. (18) in 2013, which might show the ability of heart score to correctly categorize patients and predict their short-term outcome. the present study indicates that the incidence of mace is 6.8% in the low-risk group of patients, while backus et al. in a study titled “a prospective validation of the heart score for chest pain patients at the emergency department” reached the result of 1.7% in low-risk group (18); and in a study by mahler et al., this rate was reported to be less than 1% (14). the results of this study also indicate 85.3% incidence of adverse cardiac events in the high-risk group, which supports the studies by leite et al. (19) and melki et al., which reported that more than half of high-risk patients had adverse cardiac events (16). this is also consistent with the study by backus et al., which reports 50.1% mace in the high-risk group of patients (18). data analysis of the present study showed that there is a statistically significant relationship between heart score variables and the incidence of mace, which corresponds to the study by mahler et al., stating that the incidence of adverse cardiac events is strongly correlated with heart score (14). heart score has recently been proposed as a tool for classifying patients with chest pain in high, moderate, and lowrisk groups. but based on the findings of this study, it seems that using this tool should be considered with caution and as an adjuvant tool along with overall judgments of in charge physicians. 5. limitations small sample size, short time period of follow-up, high number of excluded cases, and probability of selection bias might be among the most important limitations of the current study. moreover, the selection of patients for the type of intervention needed to address the mace was based on the in-charge physician’s decision and not exactly a determined standard, which may have caused errors in selection of patients. 6. conclusion based on the findings of the present study the mean heart score of acs patients with one-month mace was significantly higher than others and the incidence of mace in highrisk patients was significantly higher. but the overall accuracy of this score in predicting one-month mace in acs patients was in moderate range with 83.11% sensitivity and 66.25% specificity. 7. declarations 7.1. acknowledgments we hereby acknowledge and appreciate the sincere cooperation of all the authorities and staff of imam hossein hospital, the emergency ward personnel, and all the sincere colleagues who helped us in gathering and retrieving the patients’ data. 7.2. funding no funds were received for this project. 7.3. conflict of interest the authors hereby state that there is no conflict of interest in/regarding the present study. 7.4. author contribution all authors meet the standard criteria of authorship contribution based on the recommendations of the international committee of medical journal editors. 7.5. ethics approval the patient’s medical records and personal information remained confidential and any use of this information in any way besides this project was prevented (ethics code: ir.sbmu.msp.rec.1397.250). references 1. clark jc, lan vm. heart failure patient learning needs after hospital discharge. applied nursing research. 2004;17(3):150-7. 2. tahmasebi h, mahmoodi g, mokhberi v, hassani s, akbarzadeh h, rahnamai n. the impact of aromatherapy on the anxiety of patients experiencing coronary angiography. zahedan j res med sci. 2012;14(3):e93565. 3. black jm, hawks jh, keene am. medical-surgical nursing: clinical management for positive outcomes: wb saunders; 2001. 4. niknejad r, mirmohammad-sadeghi m, akbari m, ghadami a. effects of an orientation tour on preoperthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e31 ative anxiety in candidates for coronary artery bypass grafting: a randomized clinical trial. arya atherosclerosis. 2019;15(4):154. 5. hadaegh f, harati h, ghanbarian a, azizi f. prevalence of coronary heart disease among tehran adults: tehran lipid and glucose study. emhj-eastern mediterranean health journal, 15 (1), 157-166, 2009. 2009. 6. paul b, vitaly l, elena z, editors. new methods for healthcare system evaluation using human reliability analysis. proceedings of the human factors and ergonomics society annual meeting; 2017: sage publications sage ca: los angeles, ca. 7. freund y, goulet h, bokobza j, ghanem a, carreira s, madec d, et al. factors associated with adverse events resulting from medical errors in the emergency department: two work better than one. the journal of emergency medicine. 2013;45(2):157-62. 8. crim mt, berkowitz sa, saheed m, miller j, deutschendorf a, gerstenblith g, et al. novel emergency department risk score discriminates acute coronary syndrome among chest pain patients with known coronary artery disease. critical pathways in cardiology. 2016;15(4):13844. 9. rodríguez-lópez c, garlito-díaz h, madroñero-mariscal r, sánchez-cervilla pj, graciani a, lópez-sendón jl, et al. earlobe crease shapes and cardiovascular events. the american journal of cardiology. 2015;116(2):286-93. 10. raff gl, hoffmann u, udelson je. trials of imaging use in the emergency department for acute chest pain. jacc: cardiovascular imaging. 2017;10(3):338-49. 11. mccord j, cabrera r, lindahl b, giannitsis e, evans k, nowak r, et al. prognostic utility of a modified heart score in chest pain patients in the emergency department. circulation: cardiovascular quality and outcomes. 2017;10(2):e003101. 12. gershon ca, yagapen an, lin a, yanez d, sun bc. interrater reliability of the heart score. academic emergency medicine. 2019;26(5):552-5. 13. poldervaart jm, reitsma jb, backus be, koffijberg h, veldkamp rf, ten haaf me, et al. effect of using the heart score in patients with chest pain in the emergency department: a stepped-wedge, cluster randomized trial. annals of internal medicine. 2017;166(10):68997. 14. mahler sa, hiestand bc, goff jr dc, hoekstra jw, miller cd. can the heart score safely reduce stress testing and cardiac imaging in patients at low risk for acute coronary syndrome? critical pathways in cardiology. 2011;10(3):128. 15. six aj, cullen l, backus be, greenslade j, parsonage w, aldous s, et al. the heart score for the assessment of patients with chest pain in the emergency department: a multinational validation study. critical pathways in cardiology. 2013;12(3):121-6. 16. melki d, jernberg t. heart score: a simple and useful tool that may lower the proportion of chest pain patients who are admitted. critical pathways in cardiology. 2013;12(3):127-31. 17. gharaee r, zohari anboohi s, shiri h, nasiri m. comparison of triage effectiveness based on esi and heart scale in diagnosis of outcome in patients with chest pain. journal of babol university of medical sciences. 2019;21(1):299-305. 18. backus b, six a, kelder j, bosschaert m, mast e, mosterd a, et al. a prospective validation of the heart score for chest pain patients at the emergency department. international journal of cardiology. 2013;168(3):2153-8. 19. leite l, baptista r, leitão j, cochicho j, breda f, elvas l, et al. chest pain in the emergency department: risk stratification with manchester triage system and heart score. bmc cardiovascular disorders. 2015;15(1):1-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e56 or i g i n a l re s e a rc h comparing the characteristics of mucormycosis between cases with and without covid-19; a cross-sectional study mohammad sistanizad1,2, mohammad haji aghajani1, mehrdad haghighi3, hossein amini2, asma pourhoseingholi1, niloufar taherpour1, shadi ziaie2, sara salarian4, omid moradi5∗ 1. prevention of cardiovascular disease research center, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 3. infectious diseases and tropical medicine research center, shahid beheshti university of medical sciences, tehran, iran. 4. department of pulmonary and critical care medicine, imam hossein teaching and educational center, shahid beheshti university of medical sciences, tehran, iran. 5. department of clinical pharmacy, faculty of pharmacy, hormozgan university of medical sciences, hormozgan, iran. received: april 2022; accepted: may 2022; published online: 12 july 2022 abstract: introduction: mucormycosis as a rare but life-threatening disease with 46-96% mortality, which challenged the healthcare system during the covid-19 pandemic. this study aimed to compare the characteristics of mucormycosis between cases with and without covid-19. methods: this cross-sectional study was done in two referral hospitals, imam hossein and labbafinezhad hospitals, tehran, iran, between 21 march to 21 december 2021. data related to all hospitalized adults subject with the diagnosis of mucormycosis during the study period was collected from patients’ profiles and they were divided into two groups of with and without covid-19 based on the results of real time pcr. then demographic, clinical, and laboratory findings as well as outcomes were compared between the two groups. results: 64 patients with the mean age of 53.40±10.32 (range: 33-74) years were studied (53.1% male). forty-three (67.2%) out of the 64 subjects had a positive covid-19 pcr test. the two groups had significant differences regarding some symptoms (cough (p < 0.001), shortness of breath (p = 0.006)), acute presentation (p = 0.027), using immunosuppressive (p = 0.013), using corticosteroid (p < 0.001), and outcomes (mortality (p = 0.018), need for intubation (p < 0.001)). 22 (34.3%) patients expired during hospital admission. univariate analysis showed the association of in-hospital mortality with need for ventilation (p < 0.001), sinus involvement (p = 0.040), recent use of dexamethasone (p = 0.011), confirmed covid-19 disease (p = 0.025), mean body mass index (bmi) (p =0.035), hemoglobin a1c (hba1c) (p = 0.022), and median of blood urea nitrogen (bun) (p =0.034). based on the multivariate model, confirmed covid-19 disease (or = 5.01; 95% ci: 1.14-22.00; p = 0.033) and recent use of dexamethasone (or= 4.08, 95% ci: 1.05-15.84, p = 0.042) were independent predictors of mortality in this series. conclusion: the mucormycosis cases with concomitant covid-19 disease had higher frequency of cough and shortness of breath, higher frequency of acute presentation, higher need for immunosuppressive, corticosteroid, and ventilator support, and higher mortality rate. the two groups were the same regarding age, gender, bmi, risk factors, underlying diseases, symptoms, and sites of involvement. keywords: covid-19; mucormycosis; mortality; cross-sectional studies; risk factors; diabetes mellitus cite this article as: sistanizad m, haji aghajani m, haghighi m, amini h, pourhoseingholi a, taherpour n, ziaie s, salarian s, moradi o. comparing the characteristics of mucormycosis between cases with and without covid-19; a cross-sectional study. arch acad emerg med. 2022; 10(1): e56. https://doi.org/10.22037/aaem.v10i1.1608. ∗corresponding author: omid moradi; department of clinical pharmacy, faculty of pharmacy, hormozgan university of medical sciences, bandar abbas, iran. zip code: 7919691982 phone number: +987633710406, email: o_moradi@outlook.com, orcid: http://orcid.org/0000-0001-5754-535x. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sistanizad et al. 2 1. introduction from late 2019 to date, severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has infected many people, and more than 400 million cases of coronavirus disease 2019 (covid-19) have been reported (1). increasing cases of coinfections with bacterial and fungal pathogens have been reported in covid-19 patients (2). opportunistic infections, including aspergillosis, and mucormycosis, have been reported in patients with covid-19 (3). most of the reported cases are from india during the delta variant (b.1.617.2) outbreak. mucormycosis is an opportunistic lethal fungal infection. this fungus could infect patients with altered immune system (4). inhalation of the fungal spores in an immunocompromised patient results in angioinvasion (4, 5). many mechanisms have been proposed for the increased chance of infection by opportunistic fungi (mucorales) in hospitalized patients due to covid-19. hypoxia, diabetes mellitus, metabolic acidosis, and lymphocytopenia increase the probability of mucormycosis in covid-19 patients. also, using immunomodulating medications such as corticosteroids and biological agents could increase the risk of infection in some covid-19 patients (6, 7). the mortality rate due to mucormycosis could be as high as 90 percent (7). diagnosis and treatment of this opportunistic infection in hospitalized patients could be lifesaving, and the therapy consists of surgical and pharmacologic approaches (8). twelve hours of delay in diagnosis of the disease could be associated with a significantly increased mortality risk (9, 10). based on the above-mentioned points, this study aimed to compare the characteristics of mucormycosis between cases with and without covid-19. 2. methods 2.1. study design and setting this cross-sectional study was done in two referral hospitals, imam hossein and labbafinezhad hospitals, tehran, iran, between 21 march to 21 december 2021. data related to all hospitalized adult subjects with the diagnosis of mucormycosis (black fungus) during the study period was collected from patients’ profiles and they were divided into two groups of with and without covid-19, based on the results of real time pcr. then demographic, clinical, and laboratory findings as well as outcomes were compared between the two groups. the study was in accordance with the principles of the helsinki declaration and the ethics committee of shahid beheshti university of medical sciences approved the study protocol (ir.sbmu.retech.rec.1400.660). 2.2. participants in this study, all adults referred to the two hospitals, who were diagnosed with mucormycosis or hospitalized patients with mucormycosis complications during hospital stay were included using the census method. diagnosis of mucormycosis as a fungal disease was made by an infectious disease specialists, based on the clinical presentation and by considering specific signs and symptoms. acute mucormycosis was defined as the duration of clinical presentation of the disease being seven days or less, and the sub-acute form was defined as presence of symptoms for 7-21 days (12). in addition, all subjects were screened for the possibility of covid-19 co-infection using the standard real-time reverse-transcriptase–polymerase-chain-reaction (rtpcr) test. patients with incomplete information were excluded from the study. 2.3. data gathering data were extracted from patients’ medical records using the researcher-made checklist. the checklist contained information about demographic characteristics, history of underlying diseases, smoking status, drug history, clinical presentation, clinical signs and symptoms, baseline laboratory data, site of mucormycosis involvement, prescribed medications in the hospital, sars-cov-2 rt-pcr test result, length of hospital stay, history of sars-cov-2 infection, the time interval between initial mucormycosis clinical symptoms to diagnosis, and in-hospital mortality. data gathering and extraction were performed by trained medical staff. 2.4. statistical analysis data analysis was carried out using spss (ibm corp, released 2017. ibm spss statistics for windows, version 25.0. armonk, ny: ibm corp.). the normality of data was assessed using shapiro-wilk test and q-q plot. complete case (“cc”) analysis was used in the presence of missing data. continuous variables are described using mean ± standard deviation or median and interquartile range (iqr). categorical variables are reported as frequency and percentage. to compare continuous variables between groups, appropriate tests, including student’s t-test or mann-whitney u test, were used for normally and non-normally distributed variables, respectively. the distribution of categorical variables was evaluated between the groups using chi-squared or fisher’s exact test (if more than 25% of the variables had a frequency below 5). logistic regression was used to assess the association between in-hospital mortality and selected variables at univariate and multivariate levels. to select the potential factors for entering the multivariate model, we used a backward selection approach with p-value < 0.05. all calculations were performed at a significant level of less than 0.05 with a 95% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e56 table 1: comparing the baseline characteristics of mucormycosis between covid-19 and non-covid-19 patients variables total (n=64) covid-19 p-value yes (n=43) no (n=21) gender female 30 (100) 20 (66.7) 10 (33.3) 0.934 male 34 (100) 23 (37.6) 11 (23.4) age (years) 53.40±10.32 52.16±10.63 55.95 ±9.38 0.170 body mass index (kg/m2) 25.47±3.66 26.16 ±3.32 23.96 ±4.04 0.062 length of stay median (iqr) 16 (23.5) 20 (24) 15 (18) 0.710 symptoms sore eyes 41 (100) 27 (65.9) 14 (34.1) 0.760 swelling of eyes and face 38 (100) 25 (65.8) 13 (34.2) 0.773 blurred vision 23 (100) 16 (69.6) 7 (30.4) 0.762 cough 19 (100) 19 (100) 0 (0) <0.001 weakness 15 (100) 11 (73.3) 4 (26.7) 0.403 headache 13 (100) 9 (69.2) 4 (30.8) 0.507 fever 12 (100) 7 (56.3) 5 (41.7) 0.570 shortness of breath 12 (100) 12 (100) 0 (0) 0.006 symptoms to diagnosis median (iqr) 5 (4) 6 (6) 5 (3) 0.824 presentation acute 59 (100) 40 (67.8) 19 (32.2) 0.027 subacute 5 (100) 3 (60) 2 (40) 0.534 risk factors/ underlying smoking 31 (100) 23 (74.2) 8 (25.8) 0.247 opium 4 (100) 1 (25) 3 (75) 0.099 alcohol 2 (100) 1 (50) 1 (50) 1.000 coronary artery disease 11 (100) 10 (90.9) 1 (9.1) 0.085 diabetes mellitus 45 (100) 32 (71.1) 13 (28.9) 0.304 dyslipidemia 18 (100) 14 (77.8) 4 (22.2) 0.259 hypertension 26 (100) 17 (65.4) 9 (34.6) 0.799 drug history immunosuppressive 10 (100) 4 (40) 6 (60) 0.068 anticoagulant 4 (100) 3 (75) 1 (25) 1.000 antiplatelet aggregation 22 (100) 16 (72.7) 6 (27.3) 0.495 antidiabetic 43 (100) 30 (69.8) 13 (30.2) 0.529 antihypertensive 28 (100) 19 (67.9) 9 (32.1) 0.920 laboratory tests esr (sec) 56.34±33.50 60.32±31.74 47.94 ±36.38 0.187 albumin (g/dl) 3.19±0.58 3.18±0.64 3.22 ±0.44 0.822 hba1c (g/dl) 9.54 ±2.99 9.90±2.91 8.63 ±3.07 0.166 blood urea nitrogen (mg/dl) 38.2 (31.8) 39 (36.7) 34.6 (27.45) 0.139 blood sugar (mg/dl) 189 (211) 180 (210.75) 192 (310) 0.974 data are presented as mean ± standard deviation (sd), frequency (%), and median (iqr). esr: erythrocyte sedimentation rate; hba1c: hemoglobin a1c. confidence interval (ci). 3. results 3.1. baseline characteristics of studied cases 64 patients with the mean age of 53.40±10.32 (range: 33-74) years were studied (53.1% male). the most common underlying diseases were diabetes mellitus with 45 (70.3%), hypertension with 26 (40.6%), dyslipidemia with 18 (28.1%), and coronary artery disease with 11 (17.2%) cases. nine (13.8%) patients were hospitalized due to malignancy. the most common chief complaints were sore eyes with 41 (64.1%), swelling of the eyes and face with 38 (59.4%), blurred vision with 23 (35.9%), and cough with 19 (29.7%) cases. fiftynine (92.2%) patients had the acute presentation of mucormycosis, and 5 (7.7%) had a sub-acute presentation. the most prevalent sites of fungal involvement were orbit with 60 (93.8%) and sinus with 38 (59.4%) subjects. the median duration of hospitalization was 16 days with an iqr of 23.5, the median time from onset of covid-19 to the diagnosis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sistanizad et al. 4 table 2: comparing the management and outcome of mucormycosis between covid-19 and non-covid-19 patients variables total (n=64) covid-19 p-value yes (n=43) no (n=21) involvements sinus 38 (100) 26 (68.4) 12 (31.6) 0.799 orbit 60 (100) 39 (65) 21 (35) 0.294 pulmonary 9 (100) 7 (77.8) 2 (22.2) 0.706 cns 4 (100) 3 (75) 1 (25) 1.000 managements immunosuppressive 41 (100) 32 (78) 9 (22) 0.013* corticosteroid 33 (100) 32 (97) 1 (3) <0.001 outcomes ventilation 21 (100) 18 (85.7) 3 (14.3) <0.001 in-hospital mortality 22 (100) 19 (86.4) 3 (13.9) 0.018 cns: central nervous system. of covid-19-associated mucormycosis (cam) was 11 days with an iqr of 19.3, and the median time from onset of symptoms to diagnosis of cam was six days with an iqr of 7.8. 3.2. covid-19 vs. non-covid-19 cases forty-three (67.2%) out of 64 subjects had a positive covid19 pcr test. table 1 and 2 compare the demographic, clinical, managements, and outcomes of mucormycosis between patients with and without covid-19. two groups had significant difference regarding symptom (cough (p < 0.001), shortness of breath (p = 0.006)), acute presentation (p = 0.027), using immunosuppressive (p = 0.013), using corticosteroid (p < 0.001) and outcome (in-hospital mortality (p = 0.018), and need for intubation (p < 0.001)). 3.3. predictors of mortality 22 (34.3%) patients expired during hospital admission. univariate analysis showed the association of in-hospital mortality with need for ventilation (p < 0.001), sinus involvement (p = 0.040), recent use of dexamethasone (p = 0.011), confirmed covid-19 disease (p = 0.025), mean body mass index (bmi) (p =0.035), hemoglobin a1c (hba1c) (p = 0.022), and median of blood urea nitrogen (bun) (p =0.034). based on the multivariate model, confirmed covid-19 disease (or = 5.01; 95% ci: 1.14-22.00; p = 0.033) and recent use of dexamethasone (or= 4.08, 95% ci: 1.05-15.84, p = 0.042) were independent predictors of in-hospital mortality in this series. 4. discussion the mucormycosis cases with concomitant covid-19 disease had higher frequency of cough and shortness of breath, higher frequency of acute presentation, higher need for immunosuppressive, corticosteroid, and ventilator support, and higher mortality rate. the two groups were similar regarding age, gender, bmi, risk factors, underlying diseases, symptoms, and sites of involvement. covid-19 was an independent predictor of mucormycosis in-hospital mortality. the condition of mucormycosis, a rare invasive fungal infection, was previously a matter of concern in immunocompromised patients (13). these patients included those with hematologic malignancy, diabetes mellitus, transplant recipients, the receivers of immunosuppressive therapy and corticosteroid, and those with other immunodeficient conditions such as acquired immunodeficiency syndrome (14). with increase in the prevalence of covid-19, and using corticosteroid and other immunosuppressive utilization to treat this disease, the number of cases has raised, significantly. in this article, the most prevalent site of involvement was sinus and orbit. as previously reported, the site of involvement in mucormycosis patients is related to the predisposing condition. in patients with covid-19, rhino-orbital involvement is the most prevalent (6). this is also the most common site of involvement in patients with mucormycosis due to uncontrolled diabetes (7). involvement of other areas, such as pulmonary involvement are more commonly reported in patients with malignancy (7, 15, 16). physicians should consider this phenomenon when they examine suspected mucormycosis patients. diabetes mellitus was recognized as an important risk factor for invasive mucormycosis. in 2019, parakash h et al. reported 388 cases of mucormycosis, and diabetes was reported in 57% of these patients (17). it should be noted that the reported cases in the research had not been infected with sars-cov-2. as it was previously reported, diabetes mellitus and uncontrolled hyperglycemia are risk factors for more severe covid-19 (17). in the present study, diabetes mellitus was the most prevalent underlying condition. we should consider that patients with severe covid-19 will more often need to receive corticosteroid therapy and other immunosuppressive agents such as tocilizumab. all these factors together increase the rate of mucormycosis and a higher rate of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e56 mortality is expected. our study showed that corticosteroid therapy in these patients is linked to a higher mortality rate. based on the recommendations of the latest guidelines, corticosteroids are the cornerstone of pharmacotherapy for the patients in severe stages of covid-19 and hypoxia (18). the results of our study indicate that we should be careful about the administration of corticosteroids in high-risk patients for mucormycosis. the triad of covid-19, corticosteroid, and diabetes put these patients at increased risk for opportunistic infections such as mucormycosis. 5. limitations in assessing the results of the present study, we should consider all the possible limitations. first of all, multicentric studies with a larger sample size evaluating different populations are needed. risk factor evaluation in a population with various predisposing factors is of value. second, although we evaluated the effect of pre-hospitalization glycemic control based on hba1c, the role of glycemic control during hospitalization should be evaluated as it was shown that using insulin to control blood sugar during the hospital stay is important in covid-19 patients (19). third, we observed a higher rate of mortality in cam patients. both, severe covid-19 and mucormycosis, could be lethal, and it is not possible to evaluate the net effect of each parameter on the outcome of the patients, separately, but a higher mortality rate is seen in mucormycosis patients with covid-19. fourth, we did not examine the association of the newer immunomodulators, such as baricitinib, anakinra, or tofacitinib, and cam in highrisk patients or the effect of these agents on the outcome of cam patients. these valuable agents are used in clinics for patients with severe covid-19, but data about their association with increased risk of opportunistic infections is lacking. in this study, the diagnosis of mucormycosis was done based on clinical evaluation, and it could be proposed to confirm the diagnosis using organism identification via histopathology for further studies. 6. conclusion the mucormycosis cases with concomitant covid-19 disease had higher frequency of cough and shortness of breath, higher frequency of acute presentation, higher need for immunosuppressive, corticosteroid, and ventilator support, and higher mortality rate. the two groups were similar regarding age, gender, bmi, risk factors, underlying diseases, symptoms, and sites of involvement. covid-19 was an independent predictor of mucormycosis in-hospital mortality. 7. declarations 7.1. acknowledgments we are thankful to imam hossein and shahid labafinejad hospitals’ staff for their effort to help people and save lives during the covid-19 pandemic as the most visited university-affiliated medical centers in tehran, iran. 7.2. data availability the data is at the disposal of the corresponding author of the article and it it can be made available to the researchers upon request. 7.3. authors’ contributions ms and om designed, reviewed the study, and revised subsequent drafts. mha, mh, shz and ss were the medical consultants and participated in data acquisition. ha and nt prepared the first english draft of manuscript. ap analyzed data. all authors read and approved the final manuscript. 7.4. funding and supports this study was supported by the vice-chancellor of research and technology, shahid beheshti university of medical sciences, tehran, iran, and did not receive any funding support from secondary institutions, organizations, or companies regarding supplying medications types of equipment, technical support or any other. 7.5. conflict of interest there is none to declare. references 1. (who) who. who coronavirus (covid-19) dashboard 2022 [available from: https://covid19.who.int/. 2. kubin cj, mcconville th, dietz d, zucker j, may m, nelson b, et al., editors. characterization of bacterial and fungal infections in hospitalized patients with coronavirus disease 2019 and factors associated with health care-associated infections. open forum infect dis. 2021;8(6):ofab201. 3. song g, liang g, liu w. fungal co-infections associated with global covid-19 pandemic: a clinical and diagnostic perspective from china. mycopathologia. 2020;185(4):599-606. 4. kauffman ca, malani an. zygomycosis: an emerging fungal infection with new options for management. curr infect dis rep. 2007;9(6):435-40. 5. eucker j, sezer o, graf b, possinger k. mucormycoses. mycoses. 2001;44(7-8):253-60. 6. singh ak, singh r, joshi sr, misra a. mucormycosis in covid-19: a systematic review of cases rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sistanizad et al. 6 ported worldwide and in india. diabetes metab syndr. 2021;15(4):102146. 7. roden mm, zaoutis te, buchanan wl, knudsen ta, sarkisova ta, schaufele rl, et al. epidemiology and outcome of zygomycosis: a review of 929 reported cases. clin infect dis. 2005;41(5):634-53. 8. spellberg b, walsh tj, kontoyiannis dp, edwards j, jr., ibrahim as. recent advances in the management of mucormycosis: from bench to bedside. clin infect dis. 2009;48(12):1743-51. 9. maartens g, wood mj. the clinical presentation and diagnosis of invasive fungal infections. j antimicrob chemother. 1991;28 suppl a:13-22. 10. chamilos g, lewis re, kontoyiannis dp. delaying amphotericin b-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. clin infect dis. 2008;47(4):503-9. 11. world medical association declaration of helsinki: ethical principles for medical research involving human subjects. jama. 2013;310(20):2191-4. 12. bhanuprasad k, manesh a, devasagayam e, varghese l, cherian lm, kurien r, et al. risk factors associated with the mucormycosis epidemic during the covid-19 pandemic. int j infect dis. 2021;111:267-70. 13. mcnulty js. rhinocerebral mucormycosis: predisposing factors. laryngoscope. 1982;92(10 pt 1):1140-3. 14. sugar am. mucormycosis. clin infect dis. 1992;14 suppl 1:s126-9. 15. feng j, sun x. characteristics of pulmonary mucormycosis and predictive risk factors for the outcome. infection. 2018;46(4):503-12. 16. lee fy, mossad sb, adal ka. pulmonary mucormycosis: the last 30 years. arch intern med. 1999;159(12):1301-9. 17. prakash h, ghosh ak, rudramurthy sm, singh p, xess i, savio j, et al. a prospective multicenter study on mucormycosis in india: epidemiology, diagnosis, and treatment. med mycol. 2019;57(4):395-402. 18. agarwal a, rochwerg b, lamontagne f, siemieniuk ra, agoritsas t, askie l, et al. a living who guideline on drugs for covid-19. bmj. 2020;370:m3379. 19. khalili s, moradi o, kharazmi ab, raoufi m, sistanizad m, shariat m. comparison of mortality rate and severity of pulmonary involvement in coronavirus disease-2019 adult patients with and without type 2 diabetes: a cohort study. can j diabetes. 2021;45(6):524-30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e26 https://doi.org/10.22037/aaem.v9i1.1128 or i g i n a l re s e a rc h fibrinogen dysregulation is a prominent process in fatal conditions of covid-19 infection; a proteomic analysis mostafa rezaei-tavirani1, mohammad rostami nejad2, babak arjmand3, sina rezaei tavirani1, mohammadreza razzaghi4, vahid mansouri1∗ 1. proteomics research center, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. gastroenterology and liver diseases research center, research institute for gastroenterology and liver diseases, shahid beheshti university of medical sciences, tehran, iran. 3. cell therapy and regenerative medicine research center, endocrinology and metabolism molecular-cellular sciences institute, tehran university of medical sciences, tehran, iran. 4. laser application in medical sciences research center, shahid beheshti university of medical sciences, tehran, iran. received: january 2021; accepted: february 2021; published online: 15 march 2021 abstract: introduction: molecular pathophysiology of covid-19 is not completely known. expression changes in patients’ plasma proteins have revealed new information about the disease. introducing the key targeted plasma protein in fatal conditions of covid-19 infection is the aim of this study. methods: significant differentially expressed proteins (deps) in the plasma of cases with a fatal condition of covid-19 were extracted from an original article. these proteins were included in a network via string database along with 100 first neighbor proteins to determine central nodes of the network for analyzing. results: queried and added proteins were included in a scale free network. three hub nodes were identified as critical target proteins. the top queried hub proteins were chains of fibrinogen; fibrinogen alpha chain (fga), fibrinogen gamma chain (fgg), and fibrinogen beta chain (fgb), which are related to the coagulation process. conclusion: it seems that fibrinogen dysregulation has a deep impact on the fatality of covid-19 infection. keywords: sars-cov-2; proteomics; proteins; protein interaction maps; fibrinogen cite this article as: rezaei-tavirani m, rostami nejad m, arjmand b, rezaei tavirani s, razzaghi m, mansouri v. fibrinogen dysregulation is a prominent process in fatal conditions of covid-19 infection; a proteomic analysis. arch acad emerg med. 2021; 9(1): e26. 1. introduction coronaviridiae family viruses possess a single rna genome with a maximum of 32 kilobases (1). coronaviruses have been found in many different animal cases (2, 3). several coronaviruses are pathogenic to humans with mild clinical symptoms (1); however, in november 2002, severe acute respiratory syndrome (sars), which was first reported in guangdong (4), resulted in the death of 774 patients in 37 countries (5). middle east respiratory syndrome (mers) corona virus (mers-cov ), detected in saudi arabia for the first time in 2012, led to 858 fatalities (6). recently, in 2019, a new type of corona virus called sars cov 2 was discovered, which leads to covid-19 (7). who has reported millions ∗corresponding author: vahid mansouri; proteomics research center, faculty of paramedical sciences, darband street, tajrish square, tehran, iran. email: vm1343@yahoo.com, tel: +982122718528, orcid: 0000000230443342. of confirmed cases and hundreds of thousands of deaths due to covid-19 pandemic around the world (8). in addition to the lower respiratory tract, many other organs, such as nervous system, gastrointestinal tract, liver, kidney, and lymph node, have been infected by sars-cov 2 (9). there are many symptoms for covid-19; including fever, pneumonia, and acute respiratory distress syndrome (10). pathophysiological changes such as lymphopenia (11), microthrombosis (12), cytokine release syndrome (13), and vascular coagulation have been reported in severe covid-19 cases (14). however the molecular pathogenesis of covid-19 is poorly understood despite the extensive efforts of scientists (15). pathophysiological changes during viral diseases and infections lead to alteration of plasma protein expression (16). identification of differentially expressed proteins (deps) in the plasma during covid-19 could help us understand the molecular pathophysiology of disease. understanding the molecular mechanism of the viral infection could contribute this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rezaei-tavirani et al. 2 to finding different treatment methods. proteomics, as a high throughput method, is applied to assess the effects of sars cov2 on patients’ plasma proteins. proteomic findings could be assessed as an interactome unit, which is interesting for many investigators. in such studies, a limited number of critical proteins could be identified as critical deps (17, 18). there is a limited number of nodes, known as central nodes, which are discriminated from others by their connections to first neighbors or involvement in shortest pathways (19, 20). identifying central proteins among the hubs, which are characterized by their connections with the first neighbors (21, 22) and central proteins, could assist us in gaining useful information for finding main disease biomarkers. in the present study, findings of a proteomic investigation by ting shu et al. (16), which was performed with the aim of identifying plasma biomarkers of covid-19 in fatal cases were assessed using network analysis to find the main targets of sars-cov 2. 2. methods considering fold change > 1.5 and p-value < 0.01, 42 differentially expressed proteins were extracted from data of the original article published by ting shu et al. (16). since original data about differentially expressed proteins in serum of patients relative to the healthy controls have been previously published by ting shu et al. in immunity (2020, 53 (5)), the details of data production and sampling are described in the authors report and here we only explain the methods of bioinformatic analysis. the data are related to the differentially expressed proteins of plasma in fatal cases of covid19. the queried proteins were included in a network via “protein query” of string database by cytoscape software 3.7.2. confidence score cutoff =0.4 was applied to construct the interactive network. among the 42 queried proteins 32 were recognized by string. for better resolution the network was constructed by the 32 queried proteins and 100 first neighbors from string database. the main connected component of the constructed network was analyzed using “network analyzer” application of cytoscape. the analyzed network was visualized based on degree value and the identified hub nodes correspond to the degree value. 3. results a total of 32 differentially expressed recognized proteins were assessed to construct a network using cytoscape software via protein query of string database. for better resolution, 100 first neighbor proteins extracted from string were added to construct the network (fig1). network analyzer considered topological properties including degree, betweenness centrality (bc) and stress (table 1). hub-bottleneck nodes are identified based on highest value of degree and bc. figure 1: the 32 queried proteins recognized by string database plus 100 first neighbors from string are included in a network. the nodes are laid out based on degree value; color from green to red and size increment are corresponding to increase of degree value. figure 2: network including top queried hub is extracted from string database. as the queried and added proteins were included in a scale free network, 32 hub nodes were determined as central proteins (table 1). the three top hub proteins (fga, fgg and fgf) were members of fibrinogen family. other hubs, arranged based on degree and bc, were orm1, orm2, ppbp, pf4, crp, apoa2, saa1, actb, cfb, and lcat. since centrality values of the hub nodes were highly dispersed, the three this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e26 table 1: the list of 32 top hub-bottlenecks of covid-19 fatalitybased network with their corresponding degree (k) and betweenness centrality (bc) values row query proteins k bc stress 1 fga 108 0.032 7228 2 fgg 105 0.023 6398 3 fgb 102 0.021 5830 4 orm1 92 0.014 3850 5 orm2 91 0.016 3686 6 ppbp 79 0.007 1900 7 pf4 75 0.003 1212 8 crp 52 0.004 1152 9 apoa2 49 0.003 898 10 saa1 38 0.002 642 11 actb 37 0.013 3174 12 cfb 27 0.004 1418 13 lcat 25 0.001 172 14 cetp 23 0 114 15 tln1 22 0 96 16 saa2 21 0 32 17 fgl1 20 0 38 18 cfi 17 0.01 892 19 ywhaz 15 0 86 20 ywhae 14 0.01 134 21 azgp1 13 0 2 22 s100a8 10 0 56 23 cfhr1 9 0 158 24 cfhr3 7 0 8 25 pon3 7 0 0 26 prdx6 7 0 44 27 arhgdib 4 0 6 28 tagln2 3 0 0 29 trim33 2 0 0 30 tubb1 2 0 0 31 sh3bgrl3 0 0 0 32 ugp2 0 0 0 the prioritized proteins are arranged based on degree values. top queried fibrinogen hubs with highest degree values were determined as the central nodes of the analyzed network and discussed in the more detail (table 1). degree and stress of fibrinogen chain hubs were more than others. orm1, orm2, and ppdp proteins followed fibrinogen chains, respectively. neighbor proteins of queried hubs are shown in figure 2. 4. discussion covid-19 patients with severe condition, present with intense inflammation, which is induced by acute respiratory syndrome (23) and leads to cytokine storm development. one of the main distinct features of covid-19 is coagulopathy (24), which is commonly observed among patients and is accompanied with severe thromboembolic conditions (25). coagulopathy increases d-dimer levels and leads to thromboembolism (26). the guidelines of international society of thrombosis and haemostasis recommended anticoagulant therapy for covid-19 patients (27). several fold increase in fibrinogen level is reported in severe cases of covid-19 (28). our data analysis revealed that enough connections between the studied proteins, could form a scale free network. the first neighbors added to the queried proteins provide a scale free network (figure 1). assessments indicated that the scale free network could provide useful information to distinguish a limited set of proteins among a large number of proteins (figure 2). our results demonstrated that fibrinogen chains of fga, fgg and fgb are top hub proteins related to covid-19 fatalities (table 1). on the other hand, neighbor proteins related to fibrinogen chains are apoa2, orm2, orm1 and cfp (figure 2). considering molecular pathways of the coagulation process, in which fibrinogen chains are involved, may open a window to help in treatment of disease. the role of fibrinogen in acute covid-19 cases and clot formation has been considered in researches. fibrinogen is a glycoprotein that is produced in liver as an anti-infective organ. liver overreacts during acute inflammatory phase in hospitalized covid-19 patients and secretes several reactants such as fibrinogen, c reactive protein (crp), ferritin and plenty of cytokines (29, 30). secretion of those reactants is the body’s defense mechanism against invading pathogens. in this regard, the dual function of fibrinogen is important, as it regulates antimicrobial activity of the immune cells and clot formation. mac1(cd11b/cd18) is a leucocyte integrin receptor, regulating inflammatory responses, and fibrinogen is a ligand for mac1, in addition to having coagulator functions (31). mac-1 is a receptor for covid-19 rna strand and increase in fibrinogen secretion could impregnate mac-1 to reduce the negative effects of the virus (32, 33). ko yp et al. summarized several host defensive mechanisms of fibrinogen, in summary two main mechanisms are fibrin matrix barrier formation and immune protective functions of host (34). formation of thrombosis could limit pathogen spread as a defensive mechanism and the researchers believed that localized formation of lungs thrombosis could restrict sars cov-2 virus from spreading (35). d-dimer is a product of fibrin degradation in blood after clot fibrinolysis. increase in d-dimer is accompanied by reduction of fibrinogen release from the platelets (25). a hypothesis states that in patients with covid-19 and other infectious diseases, increase in d-dimer and decrease in the secretion of fibrinogen, lead to activation of immune responses. on the other hand, decrease in d-dimer and increase in the secretion of fibrinogen, activates the coagulation mechanism and thrombi formation (36). among the key genes that interact with ddimer, fibrinogen level, and coagulation process, fga, fgg, and fgb are prominent. although additional gene clusters help govern d-dimer and fibrinogen count and thrombosis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rezaei-tavirani et al. 4 in covid-19 patients (37). high circulating level of fibrinogen has been linked to covid-19 coagulopathy; however, jecko thachi et al. believed that in covid-19 patients fibrinogen is probably increased to protect the host (36). c reactive protein (crp) released by liver is anti-infective and increases in acute phase of covid-19, along with ferritin and fibrinogen, as a defense mechanism against pathogens (30). our results revealed the indirect connection of crp with fgb via orm2 protein (fig2). cpr forms a complex with histones to protect them from endothelial damage resulting from edema and thrombosis in hosts suffering from covid19 (38). researches believed that evaluating crp or fibrinogen levels in addition to other conventional markers could be useful for prediction of cardiovascular disease in patients with intermediate risk factors (39). orosomucoid isoforms (orm1 and orm2) are inducers of m2 macrophages and increase in various infections (40)(41). our results also revealed a connection between orm1 and orm2 and fibrinogen chains (figure 2). this connection may be related to severe infection in fatal covid-19 cases. overall, the role of acute infections in covid-19 patients, with regard to the secretion of fibrinogen and other prominent proteins, can be evaluated in future investigations. 5. conclusion it can be concluded that activation of the clotting and embolism mechanisms along with fibrinogen secretion in patients with covid-19 are the prominent processes in fatal cases. 6. declarations 6.1. acknowledgment this project was supported by shahid beheshti university of medical sciences. 6.2. authors’ contributions all authors have contributed equally in the project administration. final revision was done by vahid mansouri and mostafa rezaei tavirani and verified by all authors. 6.3. conflict of interest there is no conflict of interest. 6.4. funding and supports this research was supported by shahid beheshti university of medical sciences with the ethics code number: ir.sbmu.retech.rec.1399.356 references 1. su s, wong g, shi w, liu j, lai ac, zhou j, et al. epidemiology, genetic recombination, and pathogenesis of coronaviruses. trends in microbiology. 2016;24(6):490-502. 2. cavanagh d. coronavirus avian infectious bronchitis virus. veterinary research. 2007;38(2):281-97. 3. ismail m, tang y, saif y. pathogenicity of turkey coronavirus in turkeys and chickens. avian diseases. 2003;47(3):515-22. 4. peiris j, guan y, yuen k. severe acute respiratory syndrome. nature medicine. 2004;10(12):s88-s97. 5. chan-yeung m, xu r. sars: epidemiology. 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against the toxicity of circulating histones. the journal of immunology. 2013;191(5):2495-502. 39. collaboration erf. c-reactive protein, fibrinogen, and cardiovascular disease prediction. n engl j med. 2012;367(14):1310-20. 40. shibata y, tamura k, ishida n. in vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of α1-acid glycoprotein, in connection with its high level in tumor-bearing mice. cancer research. 1983;43(6):2889-96. 41. kosmidis ci, chandrasekar ph. management of grampositive bacterial infections in patients with cancer. leukemia & lymphoma. 2012;53(1):8-18. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e38 br i e f re p o rt pan vs. selective computed tomography scans in management of multiple trauma patients; a brief report anita sabzghabaei1, majid shojaee2, hamid kariman2, kamran heydari1, mohammad manouchehrifar1, sirus sohrabi3∗ 1. department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, shahid beheshti hospital, qom university of medical sciences, qom, iran. received: february 2016; accepted: march 2016; published online: 11 january 2017 abstract: introduction: using pan or selective computed tomography (ct) scan in management of multiple trauma patient is a matter of debate. therefore, the present study was designed aiming to compare the findings of pan and selective ct scans in management of multiple trauma patients. methods: this is a prospective cross-sectional study, on patients presented to the emergency department (ed) of shohadaye haftome tir hospital, tehran, iran, following blunt multiple trauma over a 1-year period, from march 2014 to march 2015. findings regarding presence or absence of injury in head, face, neck, chest, abdomen and hip were compared between patients that underwent pan and selective ct using spss 21. results: 443 patients with the mean age of 34.54 ± 17.88 years were evaluated (78% male). 248 (56%) patients underwent selective ct scan and 195 (44%) underwent pan ct scan. the 2 groups were similar regarding vital signs and mean age. mean hospital length of stay was 21.05 ± 24.64 days for selective ct scan group and 18.18 ± 22.75 days for the other one (p = 0.209). a significant difference was only seen regarding findings of chest injury between the 2 groups (p < 0.001). in other cases a proper overlap was seen between findings of the 2 groups. conclusion: based on the results of the present study, it seems that doing selective ct scan yields results similar to pan ct in detection of head and face, neck and abdomen and hip injuries in multiple trauma patients. however, using pan ct in these patients led to 16% increase in detection and diagnosis of traumatic intra-thoracic injuries. keywords: tomography, x-ray computed; multiple trauma; whole body imaging; emergency service, hospital; diagnostic techniques and procedures © copyright (2017) shahid beheshti university of medical sciences cite this article as: sabzghabaei a, shojaee m, kariman h, manouchehrifar m, heydari k, sohrabi s. pan vs. selective computed tomography scans in management of multiple trauma patients; a brief report . 2017; 5(1): e38. 1. introduction m odern trauma care puts an emphasis on diagnosis and treatment of injuries in the shortest time possible. computed tomography (ct) scan is one of the most effective techniques in modern medicine, which is helpful in this regard (1-3). despite the high capacity of this type of imaging in injury detection, we should note that the new generation of ct scan devices are very expensive and have a high maintenance cost. therefore, it is very important ∗corresponding author: sirus sohrabi; emergency department, shahid beheshti hospital, shahid beheshti avenue, qom, iran; tel/fax: 00989188343392; email: s29.sohrabi@gmail.com. to do the scan in necessary cases to avoid unnecessary costs and aid in rapid and correct medical decision making. this is even more important in emergency cases, such as trauma patients, where rapid decisions can save a patient’s life (3-6). in cases of multiple-organ trauma, the required scan may be either selective (scan from a pre-determined point) or nonselective (whole body scan from head to hip). due to its more accurate diagnosis, detection of hidden injuries in asymptomatic cases and aid in more rapid and correct decision making, pan ct scan is very interesting for some physicians (6, 7). however, requesting imaging is accompanied by exposing the patient to a high dose of radiation (7). if the hidden injuries detected in pan ct scan are not clinically significant and do not make a difference in management of the patients, selective ct scan can be used instead, to decrease this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s29.sohrabi@gmail.com a. sabzghabaei et al. 2 costs and radiation received and its side effects (7, 8). nevertheless, some studies do not agree, and believe that selective ct scan is not capable of detecting all injuries caused by blunt trauma (9, 10). therefore, the present study was designed aiming to compare the findings of pan and selective ct scans in management of multiple trauma patients. 2. methods 2.1. study design and setting this study is a prospective cross-sectional one, with the aim of comparing pan and selective ct scan findings in patients presented to the emergency department (ed) of shohadaye haftome tir hospital, tehran, iran, following blunt multiple trauma over a 1-year period, from march 2014 to march 2015. non-randomized convenience sampling was used, however since the main researcher’s shifts were well-distributed regarding day or night, and holiday or weekday, patient inclusion was most probably random and unbiased. based on the protocol of the hospital, both types of imaging were routinely used in management of patients, according to the in-charge physician’s preference. decisions regarding doing ct scan were usually made based on request from the senior emergency medicine resident and approval of the incharge surgeon, and the researchers did not interfere with the routine diagnosis and treatment procedures. all multiple trauma cases caused by falling or traffic accidents, who underwent selective or pan ct scan were included. in cases of selective ct scan, for ruling out the probability of other organ injuries, repeated physical examination, clinical decision rules (11, 12), plain radiography, and ultrasonography were used. in these cases, patients were followed until the final diagnosis regarding the presence or absence of injury in organs that were not scanned, was confirmed. the final decision in this regard was made by the senior emergency medicine resident and the in-charge surgeon. after completion of diagnostic procedures and reaching a final diagnosis, patient data regarding presence or absence of injury in head, face, neck, chest, abdomen, and hip were gathered for both imaging protocols. to gather data, a checklist was used for each patient that consisted of demographic data (age and sex), hemodynamic status (heart rate, systolic and diastolic blood pressure), level of consciousness based on glasgow coma scale (gcs), trauma severity based on injury severity score (iss), hospital length of stay, and final findings regarding presence or absence of injury in head, face, neck, chest, abdomen and hip. interpretation of the obtained ct scans was done by the senior emergency medicine resident and in-charge surgeon. to increase the confidence, all images were re-interpreted by a radiologist. disagreements in this regard, were resolved by consulting a third person, either a radiologist or a surgeon or emergency medicine specialist. all ct scans were observed digitally via a computer monitor. to keep personal data and patient information confidential, all researchers adhered to the principles of helsinki declaration. protocol of the present study was approved by the ethics committee of shahid beheshti university of medical sciences. since the researchers only gathered the data and reports of the routine procedures for patients and did not directly interfere with diagnostic and treatment procedures, no additional cost or delay in treatment was imposed by them. 2.2. statistical analysis data were analyzed using spss version 22. mean ± standard deviation (sd) was used to report quantitative data, and frequency and percentage were reported for qualitative ones. to compare means between the 2 groups, t-test and anova were employed. p values under 0.05 were considered significant. 3. results: 443 patients with the mean age of 34.54 ± 17.88 years (1 91) were evaluated (78% male). 248 (56%) patients underwent selective ct scan and 195 (44%) underwent pan ct scan. table 1 compares baseline characteristics of the patients between the 2 groups. the 2 groups were similar regarding vital signs and mean age. despite the statistically significant difference between the groups regarding trauma severity and level of consciousness, they were not clinically important. mean hospital length of stay was 21.05 ± 24.64 days for selective ct scan group and 18.18 ± 22.75 days for the other one (p = 0.209). table 2 compares the final outcome of selective and pan ct scans regarding traumatic injuries of head, face, neck, chest, abdomen, and hip. a significant difference was only seen regarding findings of chest injury between the 2 groups. in other cases a proper overlap was seen between findings of the 2 groups. 4. discussion based on the findings of the present study, patients who underwent selective and pan ct scan were in a similar state regarding vital signs, level of consciousness, trauma severity and mean age and the final findings of the patients regarding head and face, neck, abdomen and hip were not significantly different. only in thoracic injuries, the rate of pathologic findings was significantly higher in the group that underwent pan ct scan (58% vs. 42% in selective ct scan). sufficient data is not available regarding the types of detected findings; however, the difference in thoracic findings might be due to detection of hidden hemothorax cases via pan ct scan. advances in imaging technology have been very helpful in more rapid and accurate diagnosis in recent years. using these techniques has grown in eds since it decreases the time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e38 table 1: baseline characteristics of the studied patients variable computed tomography scan p value selective pan1 age (year) 34.75 ± 16.91 34.27 ± 18.64 0.781 trauma severity* 21.96 ± 12.36 24.74 ± 13.20 0.023 heart rate (beats/minute) 94.48 ± 18.50 95.65 ± 21.87 0.540 systolic bp (mmhg) 118.40 ± 23.48 118.53 ± 22.74 0.955 diastolic bp (mmhg) 75.16 ± 12.28 74.33 ± 12.68 0.489 level of consciousness# 12.6 ± 3.66 11.34 ± 4.04 0.052 pan1 : whole body scan from head to hip, *based on injury severity score (iss), bp: blood pressure, #based on glasgow coma scale. measures are reported as mean ± standard deviation. table 2: comparison of final findings in selective and pan computed tomography (ct) scan groups regarding anatomic site of injury anatomic site of injury ct scan; n (%) p value selective pan1 head yes 124 (54.6) 103 (45.4) 0.311 no 124 (57.4) 92 (42.6) face yes 61 (57.5) 45 (42.5) 0.738 no 187 (56) 149 (44) neck yes 13 (48.1) 15 (51.9) 0.363 no 235 (56.6) 180 (43.3) chest yes 63 (42) 87 (58) < 0.001 no 185 (63.4) 108 (36.6) abdomen and hip yes 63 (53.4) 55 (46.6) 0.588 no 140 (43.2) 184 (56.8) pan1 : whole body scan from head to hip. needed for reaching a diagnosis (13-17). using spiral ct scan has reduced the patients ed length of stay from 85 minutes to 45 minutes (18). although using imaging techniques has significantly improved management of trauma patients, their protocol of use is a matter of debate due to the side effects and financial burdens (14, 15, 19). in america, it has been estimated that two third of the radiation received from imaging is from ct scan and this has increased the risk of mortality from radiation to 12.5 cases in 10000 ct scanned population (20). currently, there is no consensus regarding definite indications of using ct scan in management of trauma patients and utilization of this kind of imaging largely depends on the opinion of the in-charge physician. although pan scan imposes a high dose of radiation on the patient, sometimes correct diagnosis of injury in multiple trauma patients and saving their life is more important than the dose of radiation received. based on the results of a study, more than 50% of trauma patients with normal chest radiography showed evidence of a traumatic chest injury when underwent ct scan (however, only 8% of these injuries were clinically important). this study has strongly recommended doing ct scan for all patients with severe chest injuries (1). at the same time, non-selective ct scan has decreased waiting time, from ed arrival to receiving emergency care, for patients with severe multiple trauma (21). pan ct scan is more rapid and has higher quality in diagnosis of injuries to different parts of the body. yet, due to the high dose of radiation and expenses imposed on the patient, doing pan ct for all trauma patients is still a matter of debate. wagner et al. introduced non-selective scan as a standard method for evaluating multiple trauma patients and caputo et al. have deemed it a desirable method in managing these patients (8, 22). on the other hand, in a study by gupta et al. doing selective ct scan led to a decrease in scan frequency and few undiagnosed injuries were highly important (7). in addition, in a study by deunk et al. selective abdominal and chest scan helped a lot in making a decision in 34% of blunt trauma patients (23). based on the results of the present study, selective and pan this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. sabzghabaei et al. 4 ct scan have similar value in diagnosis of injuries in different parts of the body in trauma patients. however, pan ct scan led to a 16% increase in detection of chest trauma injuries, which is in line with the results of a similar study in this field (1). not recording the types of injuries detected and their importance in the patient’s final outcome is among the limitations of the present study, since presence of a finding such as occult pneumothorax does not make a difference in management of the patient if they are not in need of mechanical ventilation. therefore, it seems that to reach a solid decision regarding cost and benefit of these ct scan methods for trauma patients more accurate studies and analytical evaluation of the severity of the injuries not diagnosed in selective scan are needed. 5. conclusion based on the results of the present study, it seems that doing selective ct scan yields results similar to pan ct in detection of head and face, neck and abdomen and hip injuries in multiple trauma patients. however, using pan ct in these patients led to 16% increase in detection and diagnosis of traumatic intra-thoracic injuries. 6. appendix 6.1. acknowledgements the authors appreciate the insightful cooperation of emergency department staff. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding none. 6.4. conflict of interest none. references 1. exadaktylos ak, sclabas g, schmid sw, schaller b, zimmermann h. do we really need routine computed tomographic scanning in the primary evaluation of blunt chest trauma in patients with “normal” chest radiograph? journal of trauma and acute care surgery. 2001;51(6):1173-6. 2. livingston dh, lavery rf, passannante mr, skurnick jh, fabian tc, fry de, et al. admission or observation is not necessary after a negative abdominal computed tomographic scan in patients with suspected blunt abdominal trauma: results of a prospective, multiinstitutional trial. journal of trauma and acute care surgery. 1998;44(2):273-82. 3. matsubara t, fong h, burns c. computed tomography of abdomen (cta) in management of blunt abdominal trauma. journal of trauma and acute care surgery. 1990;30(4):410-4. 4. wolfman nt, 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m. [whole body spiral ct in primary diagnosis of patients with multiple trauma in emergency situations]. rofo: fortschritte auf dem gebiete der rontgenstrahlen und der nuklearmedizin. 1997;166(5):382-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e38 14. leidner b, beckman m. standardized whole-body computed tomography as a screening tool in blunt multitrauma patients. emergency radiology. 2001;8(1):20-8. 15. ptak t, rhea j, novelline r. experience with a continuous, single-pass whole-body multidetector ct protocol for trauma: the three-minute multiple trauma ct scan. emergency radiology. 2001;8(5):250-6. 16. sampson m, colquhoun k, hennessy n. computed tomography whole body imaging in multi-trauma: 7 years experience. clinical radiology. 2006;61(4):365-9. 17. wurmb t, quaisser c, balling h, kredel m, muellenbach r, kenn w, et al. whole-body multislice computed tomography (msct) improves trauma care in patients requiring surgery after multiple trauma. emergency medicine journal. 2010:emj. 2009.082164. 18. prokop a, hotte h, kruger k, rehm k, isenberg j, schiffer g. [multislice ct in diagnostic work-up of polytrauma]. der unfallchirurg. 2006;109(7):545-50. 19. philipp m, kubin k, hãűrmann m, metz v. radiological emergency room management with emphasis on multidetector-row ct. european journal of radiology. 2003;48(1):2-4. 20. kalra mk, maher mm, toth tl, hamberg lm, blake ma, shepard j-a, et al. strategies for ct radiation dose optimization 1. radiology. 2004;230(3):619-28. 21. wurmb te, fruhwald p, hopfner w, keil t, kredel m, brederlau j, et al. whole-body multislice computed tomography as the first line diagnostic tool in patients with multiple injuries: the focus on time. journal of trauma and acute care surgery. 2009;66(3):658-65. 22. caputo nd, stahmer c, lim g, shah k. whole-body computed tomographic scanning leads to better survival as opposed to selective scanning in trauma patients: a systematic review and meta-analysis. the journal of trauma and acute care surgery. 2014;77(4):534-9. 23. deunk j, dekker hm, brink m, van vugt r, edwards mj, van vugt ab. the value of indicated computed tomography scan of the chest and abdomen in addition to the conventional radiologic work-up for blunt trauma patients. journal of trauma and acute care surgery. 2007;63(4):757-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e15 br i e f re p o rt the role of pre-hospital telecardiology in reducing the coronary reperfusion time; a brief report peyman saberian1,2, nader tavakoli3∗, tayeb ramim4, parisa hasani-sharamin5, elham shams4, alireza baratloo1,6 1. prehospital emergency research center, tehran university of medical sciences, tehran, iran. 2. anesthesiology department, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. 3. trauma and injury research center, iran university of medical sciences, tehran, iran. 4. cancer pharmacogenetics research group (cpgrg), iran university of medical sciences, tehran, iran. 5. tehran emergency medical service center, tehran, iran. 6. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: november 2018; accepted: january 2019; published online: 3 february 2019 abstract: introduction: telecardiology is defined as using telecommunication for remote treatment of cardiac patients. this study aimed to assess the role of pre-hospital triage via telecardiology on coronary reperfusion time of patients with st segment elevation myocardial infarction (stemi). methods: this cross-sectional study was conducted from september, 2015 to january, 2018 in five academic referral hospitals, tehran, iran. studied patients were divided into two groups of percutaneous coronary intervention (pci) following telecardiology or pci following emergency department (ed) diagnosis of stemi and time to reperfusion was compared between them. results: 1205 patients with the mean age of 58.99 ± 12.33 (19-95) years entered the study (82.7% male). 841 (69.8%) cases were transferred directly to the cath-lab following telecardiology and 364 (30.2%) cases were first admitted to the ed. there was no significant difference between the groups regarding mean age (p = 0.082) and gender (p = 0.882) of participants. symptom-to-device interval time in patients who underwent pci following telecardiology was significantly lower (p < 0.001); however, the difference was not significant in the first medical contact (fmc)-to-device interval time (p = 0.268). conclusion: it is likely that the use of telecardiology in pre-hospital triage plays an important role in reducing time to pci for patients with stemi. keywords: electrocardiography; emergency medical service; st elevation myocardial infarction; telemedicine; percutaneous coronary intervention cite this article as: saberian p, tavakoli n, ramim t, hasani-sharamin p, shams e, baratloo a. the role of pre-hospital telecardiology in reducing the coronary reperfusion time; a brief report. arch acad emerg med. 2019; 7(1): e15. 1. introduction percutaneous coronary intervention (pci) is recommended as the standard treatment for acute myocardial infarction (mi) (1-3). the time interval from symptom onset until conducting reperfusion is important in reducing the cardiac necrotic area and improving prognosis. pre-hospital phase is crucial for reducing the time interval between emergency medical service (ems) contact and cardiac reperfusion. so, ∗corresponding author: nader tavakoli; department of emergency medicine, rasool-e-akram hospital, sattarkhan street, tehran, iran. tel: +989171131098; email: tavakoli2165@gmail.com it seems that ems can play an important role in this regard (4). two important aspects in this phase are the diagnosis of st segment elevation myocardial infarction (stemi) and the time interval for transferring the patients to a pci-equipped center (5). american cardiac association, american college cardiology and canadian cardiovascular committees recommend the use of 12-lead electrocardiogram (ecg) in ems (1, 4, 6). this allows rapid diagnosis of stemi in the prehospital phase, leading to quick transfer of patients to pciequipped facilities instead of hospitals that do not have the facilities, in terms of reducing mortality rates (7, 8). nowadays, many of the ems ambulances in developed and developing countries have been equipped with 12-lead ecg to reduce reperfusion time. several strategies for interpretthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 2 ing ecg have been implemented in different countries (911). some are based on the judgment and paraphrasing of the ems personnel, some based on ecg interpretation by computer to detect acute myocardial infarction and another way is interpretation of pre-hospital ecg by a consultant cardiologist (telecardiology) (12, 13). since 2016, the plan of “code-247” has been implemented by the iranian ministry of health and medical education, with the aim of reducing the time interval of pci. the plan is preparation of angioplasty equipped centers for 7 days a week and 24 hours a day to carry out pci for stemi patients in the shortest time possible, preferably less than 90 minutes. since 2017, ems ambulances have been equipped with a 12lead electrocardiogram and the ecg report has been sent to a cardiologist. therefore, stemi patients have been directly transferred to the angioplasty ward (cath-lab) and undergone primary angioplasty. the current study was designed to assess the effect of pre-hospital triage via telecardiology on reperfusion time in patients with stemi. 2. methods 2.1. study design and setting this cross-sectional study was conducted from september, 2015 to january, 2018 in five academic referral hospitals (rasool–akram, sina, imam khomeini, imam hosein, modarres) equipped with 24-hour pci facilities in tehran, iran. studied patients were divided into two groups of pci following telecardiology or pci following emergency department (ed) diagnosis of stemi and the time to reperfusion was compared between them. the study protocol was approved by ethical committee of iran university of medical sciences (ir.iums.rec.1397.956). the investigators did not interfere with patients’ management. all the information were anonymous and kept confidential and only generally used and analyzed. 2.2. participants all patients transferred to the mentioned hospitals by ems with diagnosis of stemi undergoing pci were included. sampling was done in a consecutive manner and there was no exclusion criterion. patients were divided into two groups: 1) patients who underwent pci following telecardiology; 2): patients who did not undergo an electrocardiogram in an ambulance and were transferred to the ed. in the first group, ecg was done on the patient’s bedside and sent to a cardiologist in the ems center, which is known as telecardiology. then, if the patient was diagnosed with stemi, the patient was directly transferred to a pci-equipped center. these patients were directly admitted to cath-lab and ed was bypassed. in the second group, patients were transferred to the ed without undergoing ecg on the prehospital setting. the diagnosis of stemi was made by an ed physician. after primary emergency medical care and cardiologist’s visit, if stemi was confirmed, he/she would be referred to angioplasty ward. 2.3. definitions symptom-to-device: the time interval between the onset of patients’ symptoms to pci. first medical contact (fmc)-todevice: the time interval between the first time a technician attends the patient’s bedside to pci. 2.4. data collection a two-part checklist was prepared for recording patients’ baseline characteristics and main data. the time records in this study included: 1) onset of symptoms; 2) fmc time; 3) pci time. arrival and departure to the triage unit, ecg performance, angiographic ward admission and angioplasty times were recorded digitally and manually by the nurses. registered pre-hospital emergency times, mission forms and time recorded by global positioning system (gps) were matched to the time recorded in the hospital system for validation of data. 2.5. statistical analysis statistical analyses were performed using the ibm spss software package, version 22 (spss inc., chicago, il, usa). values were expressed as frequency (number and percentage) or mean ± standard deviation (sd), as appropriate. chisquare tests were used for comparisons of categorical variables, whereas mann–whitney u and its parametric equivalent (independent t-test) were used to compare numerical variables. shapiro–wilks test and q-q plot were used to check the normality of the variables; then according to the establishment of assumptions, parametric or nonparametric test was applied. p-value<0.05 was considered statistically significant. 3. results: a total of 1205 patients with the mean age of 58.99 ± 12.33 (19-95) years entered the study (82.7% male). 841 (69.8%) cases were transferred directly to the cath-lab following telecardiology and 364 (30.2%) cases were first admitted to ed. there was no significant difference between groups regarding the mean age (p = 0.082) and gender (p = 0.882) of participants (table 1). the findings revealed that the incidence of symptoms was more frequent on about 10 am, 4 pm, and 12 am. symptom-to-device time was significantly lower in patients who underwent pci following telecardiology (p < 0.001); however, the difference was not significant regarding fmc-to-device time (p = 0.268) (table 1, figure 1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e15 table 1: demographic characteristics of participants in the two groups variables telecardiology (n=841) normal* (n=364) p-value age (year) mean ± sd 58.97 ± 12.23 59.04 ± 11.56 0.082 gender n (%) male 696 (82.8) 300 (82.4) 0.886 female 145 (17.2) 64 (17.6) onset of symptoms (o’clock) 0 6 204 (24.4) 57 (33.5) 6 12 225 (26.9) 54 (31.8) 0.006 12 18 262 (31.3) 34 (20.0) 18 24 145 (17.3) 25 (14.7) times (minutes) symptom-to-device 181.2 ± 139.5 281.6 ± 227.3 <0.001* fmc-to-device 100.4 ± 68.7 122.8 ± 113.0 0.268 * patients who had not undergone electrocardiography in the ambulance and were transferred to the emergency department. fmc: first medical contact. data are presented as mean ± standard deviation (sd) or frequency (%). figure 1: distribution of symptom-to-device and first medical contact (fmc)-to-device times in the two studied groups. 4. discussion the present study showed that telecardiology in the prehospital setting and rapid transportation to the catheterization ward caused a significant reduction in the time to cardiac reperfusion for patients. using telemedicine has been advocated for various fields in existing literature and it has been more than a decade since the first time telemedicine was used to diagnose and treat acute mi (14, 15). following a retrospective analysis on 280 consecutive stemi patients treated with pci in a rural area of usa, kahlon et al. found that pre-hospital ecgs decreased fmc-to-device by 50%, compared with those who were taken to the nearest hospital which was not a pci-equipped center by the ems. in our study, although the difference between the two studied groups was significant, it was not 50%. this difference might be due to the fact that all the patients in our study, whether using telecardiology or not, were transferred to a pci-equipped center, while the studied patients in kahlon et al. study who did not undergo an ecg in prehospital setting were transferred to a non pci-equipped center and needed to be transported to another center. in contrast to the kahlon et al. study in which most of the studied patients (63.4%) had not undergone a prehospital ecg, most of our studied patients (69.8%) had undergone ecg and were transported after using telecardiology (5). brunetti et al. conducted a similar study in italy on 297 consecutive patients with stemi transferred by ems and reported that mean time-to-balloon in stemi patients in ed without tele-medicine support was almost thrice those admitted with pre-hospital triage using telecardiology in the same center. an interesting point in brunetti et al. study is that both groups were treated within the recommended 90-120 minutes. unfortunately, in the current survey the mean of symptom-to-device intervals in both studied groups were more than 3 hours. this lost time is mostly due to the delay from the onset of the patient’s symptoms to the emergency call. however, the fmc-to-device was almost 2 hours in both groups of the current study, which is considerable and may have resulted from limited pci-equipped centers, the long distance that the ambulance this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 4 should usually go from the scene to hospital, and heavy traffic jam in tehran city (16). according to previous studies, it’s almost safe to say that the pre-hospital triage based on 12-lead electrocardiogram and telecardiology and direct transportation of stemi patients to hospitals equipped with 24-hour pci facilities can significantly reduce symptom-to-device interval and improve the prognosis of patients with acute mi (17, 18). also, the findings of the current study showed that equipping ambulances with electrocardiogram device and the possibility of telecardiology by pre-hospital staff reduced the time of the fmcto-device. patients transferred via ems with telecardiology possibility had a greater chance of cardiac reperfusion in the standard golden time (less than 90 minutes). it should be noted that the prognosis of patients with acute myocardial infarction is one of the important factors determining the effectiveness of pre-hospital triage design based on electrocardiogram and telecardiology. it is suggested that future studies should aim at assessing the effect of telecardiology on mortality and morbidity rates and overall survival of stemi patients. 5. limitations the process of registration of data in the information system was done by hospital staff so there was no possibility of detecting a registration error. the transfer distance of patients could not be compared due to the lack of transit distance records. in pre-hospital triage based on telecardiology program of ems of tehran, patients diagnosed with stemi were transferred to the pci-equipped hospitals, which may have been located far away from the scene, instead of non pciequipped centers close to the scene. yet, according to the emergency protocols, patients without telecardiology should be transferred to the closest hospital, which may not have been a 24 hour pci-equipped center. this can cause bias in comparing fmc-to-device interval time between our two studied groups. to better compare the effectiveness of telecardiology on fmc-to-device interval time, it is suggested to compare cardiac patients without telecardiology transferred to non-pci centers with cardiac patients with telecardiology and transferred to pci-equipped centers. 6. conclusion: it is likely that the use of telecardiology in pre-hospital triage plays an important role in reducing time of pci for patients with acute myocardial infarction with st segment elevation. therefore, telecardiology can be used for the suspected stemi patients to rapidly treat them and reduce complications due to delayed treatment. 7. appendix 7.1. acknowledgements none. 7.2. author contribution authors met the standard criteria for authorship based on the recommendations of the international committee of publishers of medical journals. authors’ orcids nader tavakoli: 0000-0002-5767-7771 tayeb ramim: 0000-0002-8929-9357 alireza baratloo: 0000-0002-4383-7738 7.3. funding this study was supported by a grant received from tehran ems center. 7.4. conflict of interest none. references 1. ibanez b, james s, agewall s, antunes mj, bucciarelliducci c, bueno h, et al. 2017 esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc). european heart journal. 2018;39(2):119-77. 2. kristensen sd, aboyans v. 2017 esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment 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13. brown jp, mahmud e, dunford jv, ben-yehuda o. effect of prehospital 12-lead electrocardiogram on activation of the cardiac catheterization laboratory and door-to-balloon time in st-segment elevation acute myocardial infarction. the american journal of cardiology. 2008;101(2):158-61. 14. baratloo a, rahimpour l, abushouk ai, safari s, lee cw, abdalvand a. effects of telestroke on thrombolysis times and outcomes: a meta-analysis. prehospital emergency care : official journal of the national association of ems physicians and the national association of state ems directors. 2018;22(4):472-84. 15. brunetti nd, scalvini s, acquistapace f, parati g, volterrani m, fedele f, et al. telemedicine for cardiovascular disease continuum: a position paper from the italian society of cardiology working group on telecardiology and informatics. international journal of cardiology. 2015;184:452-8. 16. brunetti nd, di pietro g, aquilino a, bruno ai, dellegrottaglie g, di giuseppe g, et al. pre-hospital electrocardiogram triage with tele-cardiology support is associated with shorter time-to-balloon and higher rates of timely reperfusion even in rural areas: data from the baribarletta/andria/trani public emergency medical service 118 registry on primary angioplasty in st-elevation myocardial infarction. european heart journal acute cardiovascular care. 2014;3(3):204-13. 17. bennin ck, ibrahim s, al-saffar f, box lc, strom ja. achieving timely percutaneous reperfusion for rural stelevation myocardial infarction patients by direct transport to an urban pci-hospital. journal of geriatric cardiology : jgc. 2016;13(10):840-5. 18. chan aw, kornder j, elliott h, brown ri, dorval jf, charania j, et al. improved survival associated with prehospital triage strategy in a large regional st-segment elevation myocardial infarction program. jacc cardiovascular interventions. 2012;5(12):1239-46. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results: discussion limitations conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e39 rev i ew art i c l e orthopedic trauma during pregnancy; a narrative review meisam jafari kafiabadi1,2, amir sabaghzadeh1, seyyed saeed khabiri1, mehrdad sadighi1, amir mehrvar2, farsad biglari1∗, adel ebrahimpour1,3 1. department of orthopedics surgery, shohada-e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of orthopedics surgery, taleghani hospital research development committee, shahid beheshti university of medical sciences, tehran, iran. 3. physiotherapy research center, shahid beheshti university of medical sciences, tehran, iran. received: march 2022; accepted: april 2022; published online: 18 may 2022 abstract: introduction: blunt traumas, like road accidents and falls, are common causes of injuries to pregnant women, and the major risk factors are young age and low socioeconomic level. due to physiological and anatomical changes specific to pregnancy, such as changes in blood pressure and hemoglobin drop, trauma management involves certain complexities. physical trauma is estimated to cause at least 1 complication in every 12 pregnancies. this study aims to evaluate orthopedic trauma during pregnancy and appreciate the different approaches to circumvent the resultant challenges. methods: we reviewed 55 articles, published on orthopedic trauma during pregnancy between 2011 and 2021. the articles were identified by searching pubmed, google-scholar, scopus, and science-direct. we utilized the search terms: fall in pregnancy, traumas in pregnancy, motor vehicle accident/crash in pregnancy, blunt trauma in pregnancy, pregnant trauma patient, penetrating injury during pregnancy, assault, interpersonal violence in pregnancy, and mortality and pregnancy. results: according to available reports, after stabilizing the pregnant patient, diagnostic procedures, including radiography, and even gadolinium-based techniques when needed, can be performed to examine extensive trauma. in contrast to elective orthopedic surgery, emergency orthopedic surgeries, including reduction of open fractures, should be performed promptly. conclusion: based on our investigation, pregnant women with orthopedic injuries that are severe, or even seemingly less severe, experience significantly increased adverse pregnancy outcomes, which include preterm birth, placental abruption, poor infant condition at birth, infant death, and even maternal death. keywords: orthopedic procedures; wounds and injuries; pregnancy cite this article as: jafari kafiabadi m, sabaghzadeh a, khabiri ss, sadighi m, mehrvar m, biglari f, ebrahimpour a. orthopedic trauma during pregnancy; a narrative review. arch acad emerg med. 2022; 10(1): e39. https://doi.org/10.22037/aaem.v10i1.1573. 1. introduction trauma is referred to as an externally triggered injury and is one of the major non-obstetric reasons leading to death during pregnancy (1). in orthopedic medicine, trauma or orthopedic trauma is characterized as a serious injury to the parts of the locomotor or musculoskeletal system (2). physical trauma is estimated to complicate 1 in every 12 pregnancies (3). the most familiar triggers of trauma in pregnancy comprise car accidents, falls, and violent assaults (4). lifethreatening maternal trauma is associated with a 40% to 50% ∗corresponding author: farsad biglari; department of orthopedics surgery, shohada-e tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. phone: +989125193843, email: biglari.farsad@gmail.com, orcid: http://orcid.org/0000-0003-0586-6236. fetal loss, implying that both mother and fetus are at risk (1). therefore, caring for the obstetric patient who suffers a traumatic injury is one of the most challenging scenarios for both nursing and medical staff. physiological changes in pregnancy might have an enormous effect on diagnosis and treatment. for example, circulating blood volume increases from the 6th week of gestation and peaks at approximately the 32nd week. hence, during resuscitation, it can take up to 50% more volume to cause changes in hemodynamic status (5). managing pregnant patients with orthopedic trauma poses challenges that should be carefully considered to protect both the mother and the developing infant. physiological changes during pregnancy, risk of radiations, and recommendations for monitoring should be focused on during the perioperative and intraoperative processes. in this article, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. jafari kafiabadi et al. 2 we focused on the epidemiology and risk factors of trauma during pregnancy and its management. we reviewed 55 articles published on orthopedic trauma during pregnancy in english language, between 2011 and 2021. the articles were identified by searching pubmed, google-scholar, sciencedirect, and scopus. the following keywords were applied: trauma in pregnancy, blunt trauma in pregnancy, penetrating injury during pregnancy, motor vehicle accident/crash in pregnancy, fall in pregnancy, assault, interpersonal violence in pregnancy, pregnant trauma patient, and mortality and pregnancy. 1.1. epidemiology and risk factors blunt trauma is the main cause of injuries among pregnant women. in a study conducted in pakistan in 2019 (6), road traffic accidents (rta) were the most common mechanism of injury (47.9%), followed by falls (31.3%). in an alternative research carried out in the united kingdom in 2016, vehicular collision and interpersonal violence were increasing causes of injury (7). in an iranian study in 2012 (8), falling (28.1%) was the most prevalent cause of injury, followed by rta (21.9%). a study conducted in america in 2011, showed that the prevalence of interpersonal violence (ipv ) during pregnancy spans between 1-20%, with the domestic partner being the abuser in most cases (9). based on the literature, risk factors for maternal trauma include: young age (<25 y) and low socioeconomic status (10), domestic violence (11), noncompliance with proper seat belt use (12), and minimal or no prenatal care in the first trimester (13). on another note, falls come second among the major causes of trauma during pregnancy (8). it was reported that women aged 30 years and below have a twofold risk of falling in pregnancy than those more than 30 years of age (14). the increase in lumbar lordosis in pregnancy moves the center of gravity forward and engenders a higher occurrence of falls. consequently, violent prodigious exertion should be abhorred in late-stage pregnancy (15). voluntary or aggressive trauma is responsible for almost 16% of traumatic lesions experienced by pregnant women (16). the occurrence of home or intimate partner abuse upsurges during pregnancy and is accumulated in the third trimester (17). depending on the region or the country, these traumas may vary in their rate. 1.2. maternal physiologic changes during pregnancy, the body undergoes many physiological and anatomical changes to adapt to the growing fetus. in the second trimester, blood pressure changes between 5–10mmhg below baseline (18), and pulse increases by 515bpm (19). hemoglobin concentration in pregnancy could fall by 5g/l due to plasma volume expansion (20), and the blood volume could increase to approximately 6l. leukocytosis and erythrocyte sedimentation rates are unreliable diagnostic markers in pregnant patients (21). besides, there is a drop in the lymphocyte count during pregnancy within the first and second trimesters and a rise within the third trimester (22). clotting factors and fibrinogen levels also increase. an increase in the clotting factors and fibrinogen results in a hypercoagulable state that is linked to a high vulnerability to thromboembolic complications (23). transient osteoporosis may prevail due to the altered physiology of pregnancy (24), increasing a patient’s susceptibility to fractures (25, 26). significant alterations in the anatomy during pregnancy principally result from the gravid uterus. hypertrophied pelvic vasculature creates the potential for massive retroperitoneal hemorrhage in the event of a pelvic fracture. uterine compression on the inferior vena-cava results in potential impairment of cardiac output, dropping to 30% during supine positioning (4). in table-1 common risks and physiological changes during pregnancy are categorized based on time. 1.3. evaluation and initial management on presentation to the emergency room, pregnant women with trauma should be stabilized and be assessed based on the severity of the trauma. if the fetus is viable (≥ 23 weeks), fetal heart rate auscultation and fetal monitoring should be performed before obstetrical consultation (15). to assess a pregnant trauma patient, a focused history should be obtained clarifying the origin of the injury. maternal last menstrual period (lmp), fetal movements, uterine contractions, and vaginal bleeding, are additional factors that should be kept in mind (15). this preliminary evaluation should be done within one minute and basic life-saving measures of trauma should be started simultaneously with the initial assessment. if conventional uninterrupted fetal observation is inaccessible, sporadic doppler measurement or bedside ultrasound calculation of a fetal heart rate is an appropriate temporary substitute. maternal status and stability take precedence over the fetal condition. first and foremost, basic life-sustaining measures through rapid assessment of the initial “a-b-cs” must be performed (27). 1.4. airway airway management and intubation in pregnant patients come with more challenges than unpregnant patients. pregnant trauma patients with a nonsecure trachea are more vulnerable to aspirate their gastric contents (15). one maternal trachea investigation performed at 12 and 38 weeks of gestation revealed that the percentage of mallampati class 4 airways (having just visible hard palate and no sight of the soft palate or uvula) was elevated by 34% between the two periods (28). in this regard, video laryngoscopy utilization, if accessible, is paramount because it allows for the maximization of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e39 first-pass success in these intubations. 1.5. breathing the marked increase in basal oxygen expenditure and utmost sensitivity of the fetus to maternal hypoxia indicate that oxygen supplementation through a nasal cannula, mask, or endotracheal tube should be performed for every pregnant trauma patient to sustain the oxygen saturation greater than 95% (15). considering the shift in the diaphragm due to pregnancy, it may be worthwhile to perform a thoracostomy tube insertion 1 to 2 intercostal spaces above normal when needed (28). 1.6. circulation in the event of continuous hemodynamic compromise, transfusion of typed and crossed blood is preferred to crystalloid solutions (29). in an emergency setting, however, type o rh-negative blood is utilized to prevent rh sensitization unless the mother is in an imminent life-threatening situation (29). precautions must be observed to prevent supine hypotension post-mid-pregnancy in the injured pregnant patient. this is achievable either by positioning the patient in the left lateral position or by manual uterine displacement, while the traumatized patient is kept in the supine position. in pregnant patients who are not hemodynamically stable, a focused assessment with sonography for trauma (fast) examination should be performed during the primary survey to assess for possible sources of bleeding. however, fast cannot detect retroperitoneal hemorrhage, which is more likely in pregnant women because of the increased blood flow to the uterus (28). any patient with a viable fetus beyond 23 weeks’ gestation should have cardiotocographic monitoring. we might consider emergent cesarean section in seriously ill trauma patients after 24 weeks’ gestation if the fetus shows non-reassuring heart rhythm. 1.7. laboratory tests normally, indicated diagnostic tests are analogous to those of non-pregnant patients. along with conventional trauma laboratory procedures, a type and screen, coagulation profile, fibrinogen, and kleihauer-betke (kb) test should be obtained. fetal-maternal hemorrhage can occur in up to 30% of pregnant patients. hence, the american college of obstetricians and gynecologists (acog) guidelines prescribe kb testing for all rh-negative pregnant trauma patients due to concerns of possible alloimmunization from 4 weeks of pregnancy (4, 30). white blood count during pregnancy is usually elevated and leukocytosis should be monitored through other clinical tests. d-dimer is often positive during pregnancy; therefore, it is not recommended to rule-out venous thromboembolism (15). 1.8. diagnostic imaging radiographic studies are recommended in indicated conditions and even gadolinium-based contrast agents are used when advantage to the mother overshadows probable fetal risks (15). this is essential to avoid non-obstetrical laparotomy given that non-obstetrical laparotomy alone catalyzes a 26% prevalence of preterm labor during the second trimester and an 82% occurrence of preterm labor in the third trimester (31). when life or limb-threatening injuries are suspected, indicated imaging should not be postponed or forsaken due to apprehensions regarding fetal radiation (4). the highest teratogenicity of ionizing radiation occurs during organogenesis (5-10 weeks). above 10 weeks, radiation will most probably impair growth or engender cns effects instead of teratogenic changes (15). nonetheless, fetuses are improbably affected by radiation beyond 15 weeks of gestation (32). table2 elucidates the fetal radiation dose from standard radiography and ct examinations. conventional chest radiographic reports in a pregnant female encompass a widened mediastinum, mild cardiomegaly, elevated diaphragms, and protrusion of the pulmonary vasculature. the pelvic x-ray reveals a widening of the symphysis pubis and sacroiliac joints (33). 83 pregnant and 167 non-pregnant patients were scrutinized in a previous chart review at an urban level 1 trauma center. the average number of initial imaging studies was 4.3 in the pregnant patients versus 6.8 in the non-pregnant group. the study showed that blunt injured pregnant trauma victims got remarkably lesser radiographic images during their consultation than their non-pregnant counterparts. however, only 1% of those pregnant patients were diagnosed with a delayed injury (34). when feasible, body ct investigations of pregnant trauma victims should be done with intravenous iodinated contrast. iodinated contrast implementation enhances the recognition of both maternal and fetal injuries by imparting vascular contrast in organs and opacification of vascular structures, as well as the placenta (31). intravenous iodinated contrast material (icm) is designated as a category b drug by the u.s. food and drug administration (fda). this implies that it has not demonstrated any side effects in neither animal nor human studies. it is more desirable to utilize icm to acquire a single diagnostic ct study rather than performing a nonenhanced ct study that may be undiagnostic and compels a repeat study. mri implementation in pregnancy may be beneficial since no fetal-related deleterious consequences have been reported following its application. even though the fda has not validated the assurance and application of mri yet, no existing records relating to adverse perinatal outcomes or long-term pediatric outcomes due to the employment of mri this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. jafari kafiabadi et al. 4 table 1: common risks and physiologic changes during pregnancy categorized based on trimesters trimester physiologic changes risk factors first central nervous system development increased white blood cell count increased erythrocyte sedimentation rate -radiosensitive development period -increased risk of teratogenesis -hypercoagulable state -increased risk of abortion with general anesthesia second relatively radio resistant fetal central nervous system increased white blood cell count increased erythrocyte sedimentation rate -increased risk of supine aortocaval compression -hypercoagulable state -increased risk of abortion with general anesthesia -increased risk of seat belt-related injury to the fetus third maternal blood volume increased by 40%–50% increased white blood cell count increased erythrocyte sedimentation rate -increased risk of supine aortocaval compression -increased risk of pregnancy-related osteoporosis -increased risk of seat belt-related injury to the fetus in pregnancy prevail. at present, gadolinium utilization in pregnancy is contentious. in rare cases, contact with gadolinium led to both pediatric and adult nephrogenic systemic fibrotic syndrome in renal insufficient patients (4). based on the standard procedure, imaging of pregnant trauma patients should replicate those of any other patient undergoing conventional radiography, ct, and mr imaging (31). 1.9. definitive treatment after the initial assessment and once the maternal hemodynamic balance is attained, monitoring the fetus should immediately commence. surgical supervision of a pregnant patient should consume the barest minimum time possible to attenuate perioperative difficulties (35). all indicated emergent injuries such as open fractures, life-threatening traumas, or fissures linked to vascular injury should be treated, regardless of the pregnancy status. elective orthopedic surgery procedures should be postponed to the postpartum period to avoid injury to the fetus (1). maternal pelvic fractures are the most common cause of fetal death amongst traumatic injuries (36). when taken in isolation, pelvic fractures do not warrant emergency cesarean section, as delivery through the vagina can be performed safely, even in the third trimester (37). pelvic fractures present a challenge because of the proximity to the uterus and the possibility of massive uterine hemorrhage and placental abruption (36). if severe bleeding from a uterine region occurs, an emergency hysterectomy should be done (1). in a pregnant trauma patient having a viable fetus, who does not respond to cardiopulmonary resuscitation or has a nonsurvivable injury, a perimortem cesarean section should be contemplated (4). a perimortem cesarean section should be considered, for maternal and fetal benefits, within 5 minutes of maternal hemodynamic instability with failure of resuscitation (38). 1.10. preoperative considerations pregnant patients are at higher risk of aspiration (39), due to progestin-mediated weakening of the lower esophageal sphincter as well as the mechanical effect of the gravid uterus. the american society of anesthesiologists’ guideline recommends that pregnant patients undergoing elective surgical operation should not have any clear liquids 2 hours before surgery and no solid food should have been consumed 6 hours to 8 hours before surgery (40). there is a remarkable increase in the risks associated with preterm labor in the perioperative period (41). if preterm birth is envisaged or considered high risk and the fetus is deemed potentially viable, prophylaxis with glucocorticoids should be considered. physically, curtailing uterine manipulation may lessen the risk of uterus contraction and subsequent preterm labor (41, 42). due to the pregnancy-induced hypercoagulable state, depending on the location of the surgery, lower leg antiembolism stockings and sequential compression device leggings should be applied before induction of anesthesia (43). tetanus vaccination poses no risk to the pregnant mother or fetus (44). a fully immunized patient who has not received a booster within 5 years should receive 0.5ml of the tetanus toxoid injected intramuscularly. a patient who has not previously received a full course should receive both the tetanus toxoid and passive immunization (1, 44). 1.11. intraoperative considerations subordinate to the probable hemodynamic repercussions of vena cava compression from an enlarged uterus, it is recommended that pregnant patients be positioned in the left lateral decubitus when possible (42). in the case of a left posterior wall acetabulum fracture typically approached from a right lateral decubitus position, prone positioning of the patient is also an acceptable alternative with ample padding of the abdomen to protect the gravid uterus (45). some fractures cannot be managed with the patient in the full left lateral decubitus position. if the patient has an unstable spine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e39 injury or a contraindication to this position, a wedge can be placed under the right side to tilt the spine and displace the uterus laterally (1, 46). based on the american college of obstetricians and gynecologists’ release, the decision to use intermittent or continuous intraoperative fetal monitoring should be based on the type of surgery, available resources, and gestational age (47). in the first and early second trimester, fetal pulses are typically monitored before and after anesthesia exposure and operative intervention, but not during the operation. in the late second and third trimesters, secondary to the viability of the fetus, continuous intraoperative fetal monitoring via transabdominal ultrasonography is generally used. if the surgical field involves the abdomen, transvaginal ultrasonography can be used (42). intraoperative electronic fetal monitoring may be advisable if the conditions below are satisfied (43): • the fetus is alive. • it is physically probable • a health care provider with obstetric privileges is available • the physician obtained informed consent to perform an emergency cesarean delivery. • the type of surgery will allow for safe disruption of the surgery for physicians to carry out an emergency delivery one of the major concerns among patients and physicians when faced with the possibility of surgery during gestation, is what effect the anesthetic and adjuvant drugs will have on the developing fetus. none of the anesthetic agents has yet been acknowledged as a specific teratogen for humans, and anesthesia increases the risk of fetal hypoxia and preterm labor. although the evidence currently remains encouraging, it is most sensible to defer elective surgery, until postpartum. if this is not possible then the first trimester should be avoided (48, 49). the choice of anesthesia depends on maternal indications, the surgical location, and the method of surgery applied (50). although general anesthesia is considered safe for use during pregnancy, the use of regional or if possible, local anesthesia may minimize fetal drug exposure (1, 50). 1.12. fracture management the prime objective in fracture fixation should be to apply the fixation procedure that entails the lowest possible radiation without endangering fracture care (51). minimally invasive percutaneous plating techniques and intramedullary nails are commonly used in orthopedic surgeries. however, these difficult techniques often require high cumulative radiation exposures. when exposure to radiation poses a high risk, open plating techniques that involve minimal irradiation should be considered (51). closed extremity fractures may be managed non-operatively, or treatment can be delayed until postpartum when appropriate (5). table 2: estimated fetal radiation dose from conventional radiographic and computed tomography examinations examination dose (mgy)* radiography cervical spine (ap, lateral) <0.001 extremities <0.001 chest (pa, lateral) 0.002 thoracic spine 0.003 abdomen (ap) (21-cm patient thickness) 1 abdomen (ap) (33-cm patient thickness) 3 lumbar spine (ap, lateral) 1 computed tomography (ct) scan head 0 chest (routine) 0.2 chest (pulmonary embolism protocol) 0.2 abdomen 4 abdomen and pelvis 25 ct angiography of the aorta 34 ct angiography of the coronary arteries 0.1 *: estimated fetal dose. ap: anterior posterior; pa: posterior anterior acute pelvic or acetabular injury during pregnancy can put both mother and fetus at increased risk of mortality (36). if a symphyseal rupture is diagnosed clinically or radiographically and the patient is hemodynamically unstable, the most important intervention is the control of internal pelvic hemorrhage with provisional closed reduction of the pelvic ring. if closed pelvic fusion and resuscitation of fluid do not reestablish hemodynamic stability, venous plexus bleeding can be repaired through an open laparotomy with retroperitoneal packing and external fixation. if the hemorrhage source is from the arteries, it may be more favorable to perform angiography (1, 36). otherwise, management includes bed rest, traction, and a pelvic sling in most patients and early mobilization with a walker should be attempted. surgical intervention on fractured pelvis is recommended when the patient suffers from an open tear in the pubic symphysis auxiliary to critical vaginal rupture, there is diastasis of the symphysis >4 cm, substantial malreduction of the pelvis, diastasis with the pelvic binder in place, or displacement of one or both sacroiliac joints. when prescribed, either peripheral fixation or open reduction and interior fixation should be performed within 3 weeks of injury. peripheral fixation decreases further damage to the uterine environment and permits the fetus to reach 34 weeks’ gestation. a supra-acetabular fixation approach can allow the patient to sit up and receive proper nursing care (1, 5). the superiority of operative fracture management for fractures involving the acetabulum has been well covered, and it is well known that excellent results are lessened in the revision or salvage surgery or when operative care is delayed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. jafari kafiabadi et al. 6 for greater than 3 weeks. with the current evidence suggesting that fracture fixation, fluoroscopy, and general anesthesia may be safely delivered to the pregnant patient, open reduction and internal fixation of the acetabulum fracture may be the treatment of choice (52). the occurrence of a pelvic fracture is not an outright indicator for avoiding vaginal delivery. if the pelvic architecture is not substantially disrupted, then a vaginal delivery can be safely performed (53). normal healing takes 8 to 12 weeks after an injury. thus, if the fracture happened during the early phases of pregnancy, vaginal delivery may be an option. if a pelvic fracture has healed without substantial residual pelvic malunion, and implants are appropriately placed within the bony pelvis, vaginal delivery should be attempted after evaluating the risk-benefit ratio for both the fetus and mother (1, 51). 1.13. prevention and outcomes pregnant trauma patients have a two-fold risk of dying after the trauma as compared to their non-pregnant counterparts. violent trauma rates tend to increase twice as much due to pregnancy, and mortality rate due to violent trauma is more than 3-fold higher compared to non-violent trauma (11). indelicate maternal trauma accounts for less than 1% of direct fetal injuries. the fetus is cushioned by the shockabsorbing effect provided by the amniotic fluid, uterus, and maternal soft tissues. a majority of fetal injuries happen during the late third trimester of pregnancy, which is characterized by shrinking of the uterine wall and thinned amniotic fluid. placental break-off is a paramount impediment of maternal trauma, existing in 5-50% of manifestations. it is the most common cause of fetal death in cases of blunt trauma. the occurrence of abruption in significant blunt trauma results in fetal death 60% of the time, second only to maternal death (15, 53). although trauma is often unpreventable, there is significant documentation that seat belt utilization during pregnancy safeguards the mother and fetus (54). as reported by many investigations, the neglect of a seat belt or other restraints increases the risk of both maternal and fetal morbidity and mortality. pregnant women who neglected the use of a seat belt during an automobile accident were 1.3-fold more likely to deliver an infant with low birth weight, had twice the possibility of experiencing disproportionate maternal hemorrhage, and were 2.8 times more certain to encounter a fetal death than women who put on a seat belt during an accident (55). in another study of pregnant patients involved in motor vehicle accidents, severe crashes in which the pregnant woman was not wearing a seat belt resulted in adverse outcomes 100% of the time (28). seatbelt placement is also an issue, with nearly 50% of fetal losses associated with improper strap placement (30). in some studies, airbag deployment during automobile accidents has been linked with fatal consequences such as uterine rupture, placental abruption, and fetal death. however, this probably reflects the magnitude of the force of the injury instead of being the cause. at this point, there are not enough data to make a recommendation about disabling airbags during pregnancy (15). 2. conclusion overall, pregnant women with orthopedic injuries that are severe or even seemingly less severe, experience a significant increase in adverse pregnancy outcomes comprising preterm birth, placental abruption, poor infant condition at birth, infant death, and even maternal death. many non-emergent pregnant orthopedic trauma patients can be managed conservatively, and delaying surgical treatment until after delivery is often a safe option. notwithstanding, when medical attention is prompted in certain cases, the orthopedic surgeon must consider the physiological changes that accompany pregnancy and the potential risks to the fetus. surgical positioning, administering medication, and diagnostic imaging are crucial considerations to ensure the best outcomes for both mother and child. 3. declarations 3.1. acknowledgments the authors kindly appreciate all staff members of imam hossein hospital who helped us to collect the data and perform this study. 3.2. authors’ contributions mjk, as and sskh did the investigation, validation, writing original draft. methodology, formal analysis, writing review & editing. ms and am: project administration, resources, methodology. fb methodology, formal analysis, writing review & editing; ae: conceptualization, resources. 3.3. funding and supports this study did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 3.4. conflict of interest the authors affirm that they do not hold any conflict of interest either in financial terms or otherwise. 3.5. ethical considerations all ethical principles were considered in this article. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): 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identifying populations at risk. am j obstet gynecol. 2013;208(6):466 e1-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction conclusion declarations references emergency. 2017; 5 (1): e7 or i g i n a l re s e a rc h trends of serum electrolyte changes in crush syndrome patients of bam earthquake; a cross sectional study saeed safari1, mehdi eshaghzade1, iraj najafi2∗, alireza baratloo1, behrooz hashemi1, mohammad mehdi forouzanfar1, farhad rahmati1 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, teharn, iran. 2. department of nephrology, dr. shariati hospital, tehran university of medical sciences, tehran, iran. received: march 2016; accepted: april 2016; published online: 8 january 2017 abstract: introduction: electrolyte imbalances are very common among crushed earthquake victims but there is not enough data regarding their trend of changes. the present study was designed to evaluate the trend of changes in sodium, calcium, and phosphorus ions among crush syndrome patients. methods: in this retrospective cross-sectional study, using the database of bam earthquake victims, which was developed by iranian society of nephrology following bam earthquake, iran, 2003, the 10-day trend of sodium, calcium, and phosphorus ions changes in > 15 years old crush syndrome patients was evaluated. results: 118 patients with the mean age of 25.6 ± 6.9 years were studied (57.3 male). on the first day of admission, 52.5% (95% ci: 42.7 62.3) of the patients had hyponatremia, which reached 43.9% (95% ci: 28.5 59.3) on day 10. 100.0% of patients were hypocalcemic on admission and serum calcium level did not change dramatically during the 10 days of hospitalization. the prevalence of hyperphosphatemia on the first day was 90.5% (95% ci: 81.5 99.5) and on the 10th day of hospitalization 66.7% (95% ci: 48.5 84.8) of the patients were still affected. conclusion: the results of the present study shows the 52.5% prevalence of hyponatremia, 100% hypocalcemia, and 90.5% hyperphosphatemia among crush syndrome patients of bam earthquake victims on the first day of admission. evaluation of 10-day trend shows a slow decreasing pattern of these imbalances as after 10 days, 43.9% still remain hyponatremic, 92.3% hypocalcemic, and 66.7% hypophosphatemic. keywords: earthquakes; crush syndrome; water-electrolyte imbalance; rhabdomyolysis; disaster victims © copyright (2017) shahid beheshti university of medical sciences cite this article as: safari s, eshaghzade m, najafi i, baratloo a, hashemi b, forouzanfar m, rahmati f. trends of serum electrolyte changes in crush syndrome patients of bam earthquake; a cross sectional study. emergency. 2017; 5 (1): e7. 1. introduction natural disasters such as earthquake are unpredictable and unavoidable happenings that bring about considerable outcomes for the population health (1). these accidents may lead to immediate death by damaging vital organs (2). however, delayed death as a result of crush syndrome, which is the second most common cause of death after earthquakes behind trauma, is a common event among earthquake survivors (3). crush syndrome happens following traumatic rhabdomyolysis, due to long-term and constant pressure on muscle bulks. breakdown of rhabdomyocyte membranes ∗corresponding author: iraj najafi; department of internal medicine, dr. shariati hospital, tehran university of medical sciences, north karegar avenue, tehran 14114 iran. tel/fax: +98 21 22721155; email: najafi63800@yahoo.com. lead to evacuation of cell contents in the blood flow and entrance of blood contents into the cell (4). this results in electrolyte imbalances such as hyperkalemia, myoglobinuria, hyperphosphatemia, hypocalcemia, etc. (5-7). existing studies show that electrolyte imbalances are frequently seen in earthquake victims with crush syndrome; among which, hyperkalemia is the most dangerous one and causes a considerable proportion of deaths among these patients (8). the correlation of other electrolyte imbalances with mortality and unfavorable outcome in the injured has also been proved. however, there is little data regarding evaluation of electrolyte imbalances in crush syndrome patients and few studies are available in this regard (9-11). the reason might be found in the chaotic situation after disasters and lack of reliable data. the present study was designed aiming to evaluate the trend of electrolyte imbalances among bam earthquake’s crush syndrome victims. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 2 2. methods 2.1. study design and setting in the present cross-sectional study, data of bam earthquake victims were retrospectively evaluated to assess the 10-day trend of changes in serum electrolyte levels including sodium, calcium, and phosphorous. 20-days trend of potassium changes was reported in another article, comprehensively. this study was approved by the ethics committee of shahid beheshti university of medical sciences, tehran, iran. during the study, researchers adhered to the principles of helsinki declaration and confidentiality of patient information. 2.2. participants immediately after bam earthquake in 2003 (kerman province, southeastern iran), a database was created based on questionnaires distributed by iranian society of nephrology with the association of international society of nephrology in 7 major cities including 15 health centers. in this database, data of 4552 earthquake victims were recorded. data included in this database were used to reach the aims of the present study. details of data gathering and management have been described in previous studies (12-14). patients that suffered from crush syndrome, whose serum electrolyte levels including sodium, potassium, calcium, and phosphorus were recorded for at least 3 days were included. patients under 15 years of age, those who had chronic kidney diseases and patients whose creatine phosphokinase (cpk) level was never measured were excluded. crush syndrome is defined as a traumatic injury leading to a creatinine level more than 1.66 mg/dl and cpk over 1000 iu/l in at least 2 measurements during hospitalization (15). sodium level under 135 meq/l was considered hyponatremia and over 145 meq/l hypernatremia. hypokalemia was defined as serum potassium level under 3.5 meq/l and levels over 5 meq/l as hyperkalemia. in addition, calcium level over 10.2 mg/dl and lower than 8.7 mg/dl were defined as hypercalcemia and hypocalcemia, respectively. normal phosphorus levels were also considered to be between 2.5 3.4 mg/dl (16). 2.3. statistical analysis data were analyzed using stata 11.0 statistical software. serum level of each evaluated electrolyte was reported as mean ± standard deviation (sd). afterwards, the prevalence of electrolyte imbalances including hyponatremia/hypernatremia, hypocalcemia/hypercalcemia, and hypophosphatemia/hyperphosphatemia were reported as percentage and 95%ci. table 1: baseline characteristics of included patients variable values age (years) 15-24 104 (88.1) 25-64 6 (5.1) ≥65 8 (6.8) time under the rubble (hours) 6.2 ± 3.4 systolic blood pressure (mmhg) 128.2 ± 21.1 diastolic blood pressure (mmhg) 79.6 ± 12.1 fluid intake (ml) 3147.0 ± 1998.0 urine output (ml) 1167.0 ± 1186.0 blood urea nitrogen (mg/dl) 102.0 ± 57.0 creatinine (mg/dl) 4.6 ± 2.3 creatine phosphokinase (iu/l) 19465 ±26078 lactate dehydrogenase (u/l) 3331 ± 2518 uric acid (mg/dl) 8.7 ± 2.9 data were presented as mean ± standard deviation or number (%). 3. results: only 118 patients with the mean age 25.6 ± 6.9 years had documented electrolyte evaluation in the first 3 days of injury (57.3 male). demographic, clinical and laboratory findings of these patients are presented in table 1. mean and sd of sodium, potassium, calcium and phosphorus in the first 3 days were 133.8 ± 9.5 meq/l, 5.7 ± 1.3 meq/l, 5.2 ± 1.6 meq/l and 6.2 ± 1.6 meq/l, respectively. trend of changes in mean level of the mentioned ions with 95% ci throughout 10 days of follow-up is shown in figure 1 and tables 2 to 4. on the first day of admission, 52.5% (95% ci: 42.7 62.3) of the patients had hyponatremia and 6.9% (95% ci: 1.9 11.9) had hypernatremia (table 2). these rates were similar until the 8th day of hospitalization. however, on the 9th and 10th days of follow-up the prevalence of hyponatremia decreased and reached 45.5% (95% ci: 30.5 60.4) and 43.9% (95% ci: 28.5 59.3), respectively (figure 1). serum calcium level did not change dramatically during the 10 days of hospitalization. the interesting point was the 100.0% (95% ci: 99.0 100.0) prevalence of hypocalcemia on the day of admission. however, even after 10 days of hospital stay, hypocalcemia was detected in 92.3% (95% ci: 81.8 100.0) of the patients. on the 10th day 3.8% (95% ci: 0.1 11.4) of the patients had hypercalcemia (table 3 and figure 1). the prevalence of hyperphosphatemia on the first day was 90.5% (95% ci: 81.5 99.5) and no case of hypophosphatemia was present. although the prevalence of hyperphosphatemia decreased as the days passed, on the 10th day of hospitalization 66.7% (95% ci: 48.5 84.8) of the patients were still affected. hypophosphatemia was seen in 3.7% (95% ci: 0.0 11.0) of the patients on the 10th day (table 4 and figure 1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e7 figure 1: mean and 95% confidence interval of serum sodium, calcium, and phosphate levels and their abnormalities during the initial 10 days after crush injury. 4. discussion: the results of the present study shows the 52.5% prevalence of hyponatremia, 100% hypocalcemia, and 90.5% hyperphosphatemia among crush syndrome patients of bam earthquake victims on the first day of admission. evaluation of 10-day trend shows a slow decreasing pattern of these imbalances as after 10 days, 43.9% still remain hyponatremic, 92.3% hypocalcemic, and 66.7% hypophosphatemic. in a study by zhang et al. that evaluated 180 victims of wenchuan earthquake, prevalence of hyponatremia was reported to be 50.6%. they expressed that hyponatremia increases the odds of mortality in earthquake victims up to 5.74 times (9). however, in other studies the reported prevalence has varied from 14.5% to 75% (10, 11, 17, 18). these differences might be due to the small sample size in some studies and various settings of hyponatremia development. apart from these differences, evaluation of the trends of hyponatremia in the present study showed that this electrolyte imbalance persisted in 43.9% of the victims even until the 10th day. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 4 table 2: trend of serum sodium concentration during the initial 10 days after admission day normal hypokalemia hyperkalemia prevalence 95% ci prevalence 95% ci prevalence 95% ci 1 52.5 42.7 62.3 40.6 31.0 50.2 6.9 1.9 11.9 2 58.4 48.7 68.1 37.6 28.1 47.1 4.0 0.1 7.8 3 53.1 43.1 63.2 40.6 30.7 50.5 6.3 1.4 11.1 4 57.6 47.4 67.8 38.0 28.1 48.0 4.3 0.2 8.5 5 55.2 44.6 65.7 41.4 31.0 51.8 3.4 0 7.3 6 58.1 46.8 69.4 31.1 20.4 41.7 10.8 3.7 17.9 7 53.4 40.5 66.4 39.7 26.9 52.4 6.9 0.3 13.5 8 53.6 40.4 66.8 42.9 29.8 56.0 3.6 0 8.5 9 45.5 30.5 60.4 45.5 30.5 60.4 9.1 0.5 17.7 10 43.9 28.5 59.3 51.2 35.7 66.7 4.9 0 11.6 total 53.7 50.2-57.2 40.3 36.8-43.8 6.0 5.3-7.7 table 3: trend of serum calcium concentration during the initial 10 days after admission day hypocalcemia normal hypercalcemia prevalence 95% ci prevalence 95% ci prevalence 95% ci 1 100.0 99.0 100.0 3.0 0.1 7.1 0.0 0.0 0.0 2 97.0 100.0 100.0 7.4 1.1 13.6 0.0 0.0 0.0 3 92.6 86.4 98.9 0.0 0.0 0.0 0.0 0.0 0.0 4 100.0 99.0 100.0 3.3 0.1 7.8 0.0 0.0 0.0 5 96.7 92.2 100.0 0.0 0.0 0.0 0.0 0.0 0.0 6 100.0 99.0 100.0 4.9 0.1 11.6 0.0 0.0 0.0 7 92.7 100.0 100.0 4.7 0.1 11.0 2.4 0.1 7.2 8 95.3 100.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 9 100.0 99.0 100.0 3.8 0.1 11.4 0.0 0.0 0.0 10 92.3 81.8 100.0 3.0 0.1 7.1 3.8 0.1 11.4 total 96.6 95.1-98.2 3.0 1.5-4.4 0.4 0.0 0.0 the reason for the high rate of hyponatremia may be found in the high volume of received fluid and its type. since serum bicarbonate should be added to the received fluid to provide urine alkalization, physicians commonly prefer half saline due to fear of increased tonicity of fluids, which can lead to hyponatremia or stabilizing it. high volume of fluid needed to produce at least 1cc urine/kg/hour, which might reach 6 -10 liters per day, can be a reason for dilutional hyponatremia. however, the range of serum sodium in these hyponatremic patients is usually between 130 -135 and is mostly asymptomatic and benign. in crush syndrome patients, hypocalcemia may occur for 2 reasons. as a result of variations in cell membrane permeability due to crush syndrome, calcium enters the cell and phosphorus leaves it. phosphorus leaving the cell and combining with calcium leads to excretion of these ions. on the other hand, kidney injury may prevent the synthesizing the active form of vitamin d and intensify hypocalcemia (19). since hypocalcemia, increases cardiotoxicity of hyperkalemia, correcting the serum concentration of this ion is of great importance (20). the interesting finding of this study is the 100% prevalence of hypocalcemia in the studied patients, although it has been asymptomatic in almost all of them. there might be 2 reasons for this high prevalence. first, the measurement reported has been of total calcium and might have yielded a different result if they were corrected based on protein level and free serum calcium was calculated. on the other hand, knowing that during 10 days only a small portion of hypocalcemia cases were corrected, patients might have suffered from underlying calcium deficiency. in addition, the role of vigorous fluid resuscitation, urine alkalization, and hyperphosphatemia (due to combining with calcium this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e7 table 4: trend of serum phosphate concentration during the initial 10 days after admission day hypocalcemia normal hypercalcemia prevalence 95% ci prevalence 95% ci prevalence 95% ci 1 0.0 0.0 0.0 9.5 0.5 18.5 90.5 81.5 99.5 2 6.0 0.2 11.7 19.4 9.8 29.0 74.6 64.1 85.2 3 3.0 0.0 7.2 13.6 5.3 22.0 83.3 74.3 92.4 4 0.0 0.0 0.0 17.5 7.6 27.5 82.5 72.5 92.4 5 0.0 0.0 0.0 17.3 6.9 27.7 82.7 72.3 93.1 6 4.1 0.0 9.7 10.2 1.6 18.8 85.7 75.8 95.6 7 2.4 0.0 7.1 16.7 5.2 28.1 81.0 68.9 93.0 8 0.0 0.0 0.0 21.4 8.8 34.0 78.6 66.0 91.2 9 0.0 0.0 0.0 34.5 16.8 52.1 65.5 47.9 83.2 10 3.7 0.0 11.0 29.6 12.0 47.2 66.7 48.5 84.8 total 2.1 0.8 3.3 17.6 14.2-21.0 80.3 76.8-83.9 and sedimentation) should not be overlooked. hyperphosphatemia is not life-threatening, however in acute phases it can lead to hypotension, hyperreflexia and even convulsion (19, 21). findings of the present study showed that most victims of earthquake had hyperphosphatemia. of course about half of hyperphosphatemic cases following vigorous fluid therapy were corrected until the 10th day of hospitalization. almost none of hyperphosphatemia cases were symptomatized. 5. limitation: a small portion of the patients entered the study due to missing data, which is a common problem among similar studies, is an important limitation. for example in wenchuan earthquake in china the serum sodium level of only 180 patients was available (9). on the other hand, the present study was multi-centric and therefore the difference in the management of the patients in various centers and not knowing the type and severity of trauma are among the most important limitations of this study. since information on management and outcome of crush syndrome patients is rare, the authors decided to do this study and publish the findings despite all the afore-mentioned limitations. 6. conclusion: the results of the present study shows the 52.5% prevalence of hyponatremia, 100% hypocalcemia, and 90.5% hyperphosphatemia among crush syndrome patients of bam earthquake victims on the first day of admission. evaluation of 10-day trend shows a slow decreasing pattern of these imbalances as after 10 days, 43.9% still remain hyponatremic, 92.3% hypocalcemic, and 66.7% hypophosphatemic. 7. appendix 7.1. acknowledgements this article has been extracted from dr. mehdi eshaghzade’s thesis for achieving his md degree from the faculty of medicine at shahid beheshti university of medical sciences. 7.2. conflict of interest none. 7.3. funding support none declared. 7.4. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. tan c, lee v, chang g, ang h, seet b. medical response to the 2009 sumatra earthquake: health needs in the post-disaster period. singapore medical journal. 2012;53(2):99-103. 2. chou y-j, huang n, lee c-h, tsai s-l, chen l-s, chang h-j. who is at risk of death in an earthquake? american journal of epidemiology. 2004;160(7):688-95. 3. erek e, sever ms, serdengecti k, vanholder r, akoglu e, yavuz m, et al. an overview of morbidity and mortality in patients with acute renal failure due to crush syndrome: the marmara earthquake experience. nephrology, dialythis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 6 sis, transplantation : official publication of the european dialysis and transplant association european renal association. 2002;17(1):33-40. 4. najafi i, hosseini m, safari s, shojaee a, sharifi a, mehrani m, et al. treatment outcomes of compartment syndrome in bam earthquake victims. iranian journal of epidemiology. 2010;5(4):26-30. 5. epstein fh, odeh m. the role of reperfusion-induced injury in the pathogenesis of the crush syndrome. new england journal of medicine. 1991;324(20):1417-22. 6. criddle lm. rhabdomyolysis pathophysiology, recognition, and management. critical care nurse. 2003;23(6):14-30. 7. safari s, najafi i, hosseini m. outcomes of fasciotomy in patients with crush-induced acute kidney injury after bam earthquake. iranian journal of kidney diseases. 2011;5(1):25. 8. sever ms, vanholder r, lameire n. management of crush-related injuries after disasters. new england journal of medicine. 2006;354(10):1052-63. 9. zhang l, fu p, wang l, cai g, zhang l, chen d, et al. hyponatraemia in patients with crush syndrome during the wenchuan earthquake. emergency medicine journal : emj. 2013;30(9):745-8. 10. waikar ss, mount db, curhan gc. mortality after hospitalization with mild, moderate, and severe hyponatremia. the american journal of medicine. 2009;122(9):857-65. 11. oda y, shindoh m, yukioka h, nishi s, fujimori m, asada a. crush syndrome sustained in the 1995 kobe, japan, earthquake; treatment and outcome. annals of emergency medicine. 1997;30(4):507-12. 12. alavi-moghaddam m, safari s, najafi i, hosseini m. accuracy of urine dipstick in the detection of patients at risk for crush-induced rhabdomyolysis and acute kidney injury. european journal of emergency medicine. 2012;19(5):329-32. 13. iraj n, saeed s, mostafa h, houshang s, ali s, farin rf, et al. prophylactic fluid therapy in crushed victims of bam earthquake. the american journal of emergency medicine. 2011;29(7):738-42. 14. najafi i, safari s, sharifi a, sanadgol h, hosseini m, rashid-farokhi f, et al. practical strategies to reduce morbidity and mortality of natural catastrophes: a retrospective study based on bam earthquake experience. archives of iranian medicine. 2009;12(4):347-52. 15. rajagopalan s. crush injuries and the crush syndrome. medical journal armed forces india. 2010;66(4):317-20. 16. kasper d, fauci a, hauser s, longo d, jameson j, loscalzo j. harrison’s principles of internal medicine 19/e (vol. 1 & vol. 2): mcgraw hill professional; 2015. 17. adams d, de jonge r, van der cammen t, zietse r, hoorn ej. acute kidney injury in patients presenting with hyponatremia. journal of nephrology. 2011;24(6):749-55. 18. donmez o, meral a, yavuz m, durmaz o. crush syndrome of children in the marmara earthquake, turkey. pediatrics international : official journal of the japan pediatric society. 2001;43(6):678-82. 19. efstratiadis g, voulgaridou a, nikiforou d, kyventidis a, kourkouni e, vergoulas g. rhabdomyolysis updated. hippokratia. 2007;11(3):129-37. 20. yokota j. crush syndrome in disaster. japan medical association journal. 2005;48(7):341-52. 21. malinoski dj, slater ms, mullins rj. crush injury and rhabdomyolysis. critical care clinics. 2004;20(1):171-92. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitation: conclusion: appendix references emergency. 2017; 5 (1): e4 or i g i n a l re s e a rc h comparison of apache ii and saps ii scoring systems in prediction of critically ill patient’s outcome hamed aminiahidashti1, farzad bozorgi1, seyyed hosein montazer1, majid baboli1∗, abolfazl firouzian2 1. department of emergency medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran. 2. department of anesthesiology, faculty of medicine, mazandaran university of medical sciences, sari, iran. received: december 2015; accepted: january 2016; published online: 8 january 2017 abstract: introduction: using physiologic scoring systems for identifying high-risk patients for mortalityhas been consideredrecently. this study was designed to evaluate the values of acute physiology and chronic health evaluation ii (apache ii)and simplifiedacute physiologic score (saps ii) models in prediction of 1-month mortality of critically ill patients. methods: the present prospective cross sectional study was performed on critically ill patientspresented to emergency department during 6 months.data required for calculation of the scores were gathered and performance of the models in prediction of 1-month mortality were assessed using stata software 11.0. results: 82 critically ill patients with the mean age of 53.45 ± 20.37 years were included (65.9% male). their mortality rate was 48%. mean saps ii (p < 0.0001) and apache ii (p = 0.0007) scores were significantly higher in dead patients. area under the roc curve of saps ii and apache ii for prediction of mortality were 0.75 (95% ci: 0.64-0.86) and 0.72 (95% ci: 0.60-0.83), respectively (p = 0.24). the slope and intercept of saps ii were 1.02 and 0.04, respectively. in addition, these values were 0.92 and 0.09 for apache ii, respectively. conclusion: the findings of the present study showed that apache ii and saps ii had similar value in predicting 1-month mortality of patients. discriminatory powers of the mentioned models were acceptable but their calibration had some amount of lack of fit, which reveals that apache ii and saps ii are partially perfect. keywords: apache; patient outcome assessment; critical illness; validation studies [publication type]; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: aminiahidashti h, bozorgi f, montazer s h, baboli m, firouzian a. comparison of apache ii and saps iiscoring systems in prediction of critically iii patient’s outcome. emergency. 2017; 5 (1): e4. 1. introduction triage of high-risk patients in emergency department (ed) and focusedand carefulmanagement of themmight result in a drop in their mortality rate (1-4). a scoring model with high screening performance characteristics can provide considerable advantages for health systems. these advantages include prediction of patient outcome, evaluating the efficiency of treatments used, efficient preand in-hospital triage, and quality improvement of treatment measures and preventive plans (6). in addition, scoring systems are able to convert the severity of an illness into a number, which results in a common understanding between physicians for taking ∗corresponding author: majid baboli; imam khomeini hospital, amir mazandarani boulevard, sari, mazandaran, iran. tel:+989113540546, email: babolimajid@gmail.com. measures and developing quality control plans regarding patient care. researchers have long attempted to design various scoring systems for this purpose. they have modified these systems to increase their efficiency, accuracy, and validity. despite significant advances in these systems, unfortunately these models have had some deficiencies and limitations(5). these limitations include complicated calculations for some models, their high number of variables, and unevaluated validity in various clinical conditions. therefore, research in this field is ongoing and new models are introduced each year. using physiologic scoring systems for identifying high-risk patients for deathhas been especially considered in recent years. to date, some physiologic scoring systems have been invented and introduced. one of the first physiologic scoring systems is a cute physiology and chronic health evaluation ii (apache ii), introduced by knaus et al. in 1985. this model is calculated based on 12 physiologic criteria, age, and previous condition of the patient. existing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com babolimajid@gmail.com h. aminiahidashti et al. 2 studies have revealed the close relation of this score with inhospital and 1-month mortalityin critically ill patients (7, 8). simplified acute physiologic score (saps ii) is among other scoring models in this field, proposed by le gall et al. this model consists of 17 variables including 12 physiologic factors, age, type of admission, and 3 variables regarding underlying diseases (9). predictive value of this model has been confirmed in different clinical conditions (10-12). these 2 models have been compared in different studies that have yielded somehow contradicting results (13-15). therefore, the present study was designed aiming to evaluate and compare the values of apache ii and saps ii models in prediction of 1-month mortality of critically ill patients presented to emergency department (ed). 2. methods 2.1. study design and settings the present prospective cross sectional study was performed on critically ill patients admitted to imam khomeini hospital, sari, iran, during february to june 2015 and assessedthe accuracy of apache ii and saps ii in prediction of in hospital mortality. ethics committee of mazandaran university of medical sciences approved the protocol of the study. informed consent was taken from patients. the researchers adhered to principles of helsinki deceleration. 2.2. participants critically ill patients were diagnosed based on appearance of patients, neurological assessment, respiratory status, cardiovascular assessment at time of admission to ed (panel 1) (16) and were enrolled using convenience sampling. participants lost to follow-up were excluded. age, gender, diagnosis impression, underlying diseases, vital signs, glasgow coma scale (gcs), urinary output, need for ventilator, andlength ofintensive care unit (icu) and hospital stay of all participantswere gathered using a pre-designed checklist. moreover, laboratory data including cell blood count (cbc), hematocrit, sodium, potassium, creatinine, bilirubin, and arterial blood gas analysis (ph, bicarbonate level, and oxygen and carbon dioxide pressure) were measured and recorded. apache ii and saps ii scores were calculated during the first 24 hours after admission based on detailed method of calculations presented in previous studies (7, 17). 30-day mortality rate was assessed using patient’s medical records and calling them by the phone. finally, patients were classified as alive and dead. 2.3. statistical analysis the number of samples was calculated to be 82 patient’s based on a 50% prevalence of mortality in critically ill patients (18-20), considering a confidence interval (ci) of 95% figure 1: mean score± standard error of apache ii and saps ii in alive and dead patients (p < 0.001). figure 2: receiver operating characteristic (roc) curve of saps ii and apache ii in mortality prediction (p = 0.24). (α = 0.05), and a power of 80% (β = 0.2). stata software version 11.0 was used for data analysis. qualitative variables are presented as frequency and percentage and quantitative factors are presented as mean and standard deviation. mannwhitney u testand fisher’s exact testwere used for comparisons. validations of the models were assessed using discriminatory powerestimation, calibration of predictive models, or a combination of the two. the discriminatory power was evaluated through calculating area under the receiver operating characteristic (roc) curve (auc) with 95% ci. general calibration of the model was also evaluated through drawing a calibration plot. in this plot, the perfect calibration is the reference line with an intercept of zero and a slope of 1. the overall performance was eventually assessed via brier score in order to evaluate predictive accuracy and reliability of the model. p value < 0.05 was considered statistically significant. 3. results 82 critically ill patients with the mean age of 53.45 ± 20.37 yearswere included (65.9% male). there were no cases of loss this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e4 panel 1: diagnostic criteria of critically ill patients appearance neurological respiratory cardiovascular gray skin unresponsive silent chest pr< 50 blue skin eyes open to pain only rr < 8 or > 30 pr > 150 mottled skin fitting agonal respiration spb< 60 rr: respiratory rateper minute;pr: pulse rate per minute, sbp: systolic blood pressure (mmhg). table 1: baseline characteristics of participants based on their outcome factor alive death p total age (year) 45.90±20.78 61.38±16.84 53.45±20.38 0.0006 gender male 29 (69.05) 25 (62.50) 54 (65.58) 0.53 female 13 (39.95) 15 (37.50) 28 (34.15) reason of hospitalization medical 24 (57.14) 36 (90.0) 60 (73.17) 0.002 surgical (emergent) 13 (30.95) 4 (10.0) 0.24 17 (20.73) surgical (elective) 5 (11.90) 0 (0.0) 5 (5.10) underlying disease none 31 (73.81) 17 (42.50) 48 (58.54) 0.06 acute renal failure 0 (0.0) 1 (2.50) 1 (1.22) carcinoma 2 (4.76) 8 (20.0) 10 (12.20) metastasis 2 (4.76) 4 (10.0) 6 (7.32) systemic weakness 3 (7.14) 5 (12.50) 8 (9.76) other 4 (9.52) 5 (12.50) 9 (10.98) reason of icu admission cardiovascular 0 (0.0) 2 (5.0) 2 (2.44) 0.007 infection 12 (28.57) 21 (52.50) 33 (40.24) respiratory 5 (11.90) 7 (17.50) 12 (14.63) neurologic 5 (11.90) 3 (7.50) 8 (9.76) multiple trauma 10 (23.81) 2 (5.0) 12 (14.63) head trauma 8 (19.05) 1 (2.50) 9 (10.98) other 2 (4.76) 4 (10.0) 6 (7.32) length of icu stay (day) 3.38 ± 3.01 6.10 ± 3.83 4.77 ± 3.70 0.0003 data are presented as mean ± standard deviation or number (%). table 2: overall performances of saps ii and apache ii model brier score sanders resolution reliability goodness of fit (%) saps ii 0.201 0.182 0.019 86.22 apache ii 0.213 0.193 0.024 84.51 to follow-up. the most common cause of hospitalization was non-surgical (73.17%). mean length of hospital stay was 4.78 ± 3.69 days and mortality rate was 48% (40 patients). table 1 shows the baseline characteristics of patients. age (p = 0.0006), reason of hospitalization (p = 0.002), and reason of icu admission (p = 0.007) correlated with mortality. mean saps ii and apache ii scores were 42.85 ± 19.67 and 19.69 ± 8.91, respectively. mean saps ii (p < 0.0001) and apache ii (p = 0.0007) scores were significantly higher in dead patients (figure 1). auc of saps ii and apache ii for prediction of mortality were 0.75 (95% ci: 0.64-0.86) and 0.72 (95% ci: 0.60-0.83), respectively (p = 0.24) (figure 2). calibration plots of these two scoring systems were presented in figure 3. the slope and intercept of saps ii were 1.02 and 0.04, respectively. in addition, these values were 0.92 and 0.09 for apache ii, respectively. overall performances of saps ii and apache ii are presented in table 2. brier score of saps ii and apache ii were 0.201 and 0.213, respectively. in addition, rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. aminiahidashti et al. 4 liability of 0.019 and 0.024 for saps ii and apache ii shows goodness of fit of them in prediction of mortality. 4. discussion results of the present study showed that apache ii and saps ii models have similar value in prediction of 1-month mortality of the patients. calibration of the 2 models had some amount of lack of fit. the two models showed partial adherence to the reference line, which indicates that the models are partially perfect in prediction of mortality. discriminatory power was acceptable for both models. in comparison with the results of the present study, alizadeh et al. have expressed that apache ii has higher value in prediction of mortality and disability resulting from intoxication compared to sapsii (13). similar findings have been reported by taghavigilani et al. (21). however, by paying close attention to the taghavigilaniet al. article, we can see that auc is 0.83 for apache ii model and 0.78 for saps ii; this difference does not seem statistically different. haddadi et al. also revealed the value of these models in patient mortality prediction (11). in contrast, sungurtekin et al. showed higher value for saps ii model compared to apache ii (22). these differences might be due to variations instudypopulation and sample size, duration offollow-up and participant selection criteria. although the discriminatory powers of both apache ii and saps ii models were in an acceptable range, findings show some amount of lack of fit. therefore, calibration of the mentioned models is not completely perfect. in line with the present study, beck et al. also displayed the external validation of the mentioned models with a similar pattern but its calibration was imperfect (23). in another study, khwannimit and greater also expressed that auc for apache ii model in prediction of critically ill patient’s mortality is 0.79, yet the calibration of this model is reported to be poor (24). this might be mainly due to disease etiology and data gathering method not being homogenous (9, 24). recent studies have shown that data gathering errors have been common, especially regarding patients with high or low apacheii and gcs scores, and this affects the predictiverole of the mentioned models (25). however, in the present study we tried to minimize data gathering errors by training the resident before initiation of sampling. possibility of selection bias in this study should not be overlooked since the study was single centric and participant selection was done using convenience sampling. other limitations of this study include etiology of participant admission not being homogenous. this affected model calibration and led to detection of some amount of lack of fit in the 2 studied models. 5. conclusion the findings of the present study showed that apache ii and saps ii had similar value in predicting 1-month mortality of patients. discriminatory powers of the mentioned models were acceptable but their calibration had some amount of lack of fit, which reveals that apache ii and saps ii are partially perfect. 6. appendix 6.1. acknowledgements the authors wish to thank all the staff of the emergency department of imam khomeini hospital, sari, iran. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interest none. 6.4. funding support none. references 1. mommsen p, zeckey c, andruszkow h, weidemann j, fromke c, puljic p, et al. comparison of different thoracic trauma scoring systems in regards to prediction of posttraumatic complications and outcome in blunt chest trauma. journal of surgical research. 2012;176(1):239-47. 2. shojaee m, faridaalaee g, yousefifard m, yaseri m, arhami dolatabadi a, sabzghabaei a, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chinese journal of traumatology. 2014;17(1):1924. 3. forouzanfar mm, safari s, niazazari m, baratloo a, hashemi b, hatamabadi hr, et al. clinical decision rule to prevent unnecessary chest x-ray in patients with blunt multiple traumas. emergency medicine australasia. 2014;26(6):561-6. 4. hashemi b, amanat m, baratloo a, forouzanfar mm, rahmati f, motamedi m, et al. validation of crash model in prediction of 14-day mortality and 6-month unfavorable outcome of head trauma patients. emergency-an academic emergency medicine journal. 2016;4:[in press]. 5. staff t, eken t, wik l, roislien j, sovik s. physiologic, demographic and mechanistic factors predicting new inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e4 figure 3: calibration plots of saps ii (a) and apache ii (b). jury severity score (niss) in motor vehicle accident victims. injury. 2014;45(1):9-15. 6. chawda m, hildebrand f, pape hc, giannoudis pv. predicting outcome after multiple trauma: which scoring system injury. 2004;35(4):347-58. 7. knaus wa, draper ea, wagner dp, zimmerman je. apache ii: a severity of disease classification system. critical care medicine. 1985;13(10):818-29. 8. giamarellos-bourboulis ej, norrby-teglund a, mylona v, savva a, tsangaris i, dimopoulou i, et al. risk assessment in sepsis: a new prognostication rule by apache ii score and serum soluble urokinase plasminogen activator receptor. critical care (london, england). 2012;16(4):r149. 9. le gall jr, lemeshow s, saulnier f. a new simplified acute physiology score (saps ii) based on a european/north american multicenter study. jama. 1993;270(24):2957-63. 10. czorlich p, sauvigny t, ricklefs f, kluge s, vettorazzi e, regelsberger j, et al. the simplified acute physiology score ii to predict hospital mortality in aneurysmal subarachnoid hemorrhage. acta neurochirurgica. 2015;157(12):2051-9. 11. haddadi a, ledmani m, gainier m, hubert h, de micheaux pl. comparing the apache ii, sofa, lod, and saps ii scores in patients who have developed a nosocomial infection. bangladesh critical care journal. 2014;2(1):4-9. 12. adamzik m, langemeier t, frey uh, gorlinger k, saner f, eggebrecht h, et al. comparison of thrombelastometry with simplified acute physiology score ii and sequential organ failure assessment scores for the prediction of 30day survival: a cohort study. shock. 2011;35(4):339-42. 13. alizadeh am, hassanian-moghaddam h, shadnia s, zamani n, mehrpour o. simplified acute physiology score ii/acute physiology and chronic health evaluation ii and prediction of the mortality and later development of complications in poisoned patients admitted to intensive care unit. basic, clinical pharmacology, toxicology. 2014;115(3):297-300. 14. brinkman s, bakhshi-raiez f, abu-hanna a, de jonge e, bosman rj, peelen l, et al. external validation of acute physiology and chronic health evaluation iv in dutch intensive care units and comparison with acute physiology and chronic health evaluation ii and simplified acute physiology score ii. journal of critical care. 2011;26(1):105.e11-.e18. 15. seak c-j, ng c-j, yen dh-t, wong y-c, hsu k-h, seak jc-y, et al. performance assessment of the simplified acute physiology score ii, the acute physiology and chronic health evaluation ii score, and the sequential organ failure assessment score in predicting the outcomes of adult patients with hepatic portal venous gas in the ed. the american journal of emergency medicine. 2014;32(12):1481-4. 16. frost p, wise mp. recognition and early management of the critically ill ward patient. british journal of hospital medicine (2005). 2007;68(sup10):m180-m3. 17. le gall j-r, lemeshow s, saulnier f. a new simplified acute physiology score (saps ii) based on a european/north american multicenter study. jama. 1993;270(24):2957-63. 18. arabi y, haddad s, goraj r, al-shimemeri a, al-malik s. assessment of performance of four mortality prediction systems in a saudi arabian intensive care unit. critical care. 2002;6(2):166-74. 19. faruq mo, mahmud mr, begum t, ahsan aa, fatema k, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. aminiahidashti et al. 6 ahmed f, et al. a comparison of severity systems apache ii and saps ii in critically ill patients. bangladesh critical care journal. 2013;1(1):27-32. 20. asadzandi m, taghizade k, tadrisi s, ebadi a. estimation of the mortality rate using the apache ii standard disease severity scoring system in intensive care unit patients. iranian journal of critical care nursing (ijccn). 2012;4(4):209-14. 21. gilani mt, razavi m, azad am. a comparison of simplified acute physiology score ii, acute physiology and chronic health evaluation ii and acute physiology and chronic health evaluation iii scoring system in predicting mortality and length of stay at surgical intensive care unit. nigerian medical journal : journal of the nigeria medical association. 2014;55(2):144-7. 22. sungurtekin h, gurses e, balci c. evaluation of several clinical scoring tools in organophosphate poisoned patients. clinical toxicology (philadelphia, pa). 2006;44(2):121-6. 23. beck dh, smith gb, pappachan jv, millar b. external validation of the saps ii, apache ii and apache iii prognostic models in south england: a multicentre study. intensive care medicine. 2003;29(2):249-56. 24. khwannimit b, geater a. a comparison of apache ii and saps ii scoring systems in predicting hospital mortality in thai adult intensive care units. journal of the medical association of thailand = chotmaihet thangphaet. 2007;90(4):643-52. 25. holt aw, bury lk, bersten ad, skowronski ga, vedig ae. prospective evaluation of residents and nurses as severity score data collectors. critical care medicine. 1992;20(12):1688-91. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e54 ca s e re p o rt facial nerve palsy with total ophthalmoplegia; a novel presentation of fungal invasion zainab mehdi1∗, nidhi bhardwaj1, jyoti aggarwal1, narinder kaur2, brijdeep singh3 1. department of general medicine, government medical college and hospital, sector -32 chandigarh, india. 2. department of radio diagnosis, government medical college and hospital, sector -32 chandigarh, india. 3. department of pathology, government medical college and hospital, sector -32 chandigarh, india. received: may 2021; accepted: may 2021; published online: 28 july 2021 abstract: mucormycosis is an expeditious invasion of a fungus of angioinvasive nature, predominant in immunocompromised individuals, often leading to organ malfunction and loss. facial nerve involvement and total ophthalmoplegia are its rare presentations. early detection and treatment can alter natural disease course and prevent potential catastrophic outcomes in diabetic patients. facial nerve palsy is mostly attributed to peripheral neuropathy in patients with advanced diabetes mellitus. it rarely raises alarm about an invasive fungal infection. here, we report the case of a 38-year-old male with type 2 diabetes mellitus, who presented to us with left lower motor neuron type facial palsy and left-sided total ophthalmoplegia due to invasive rhino-orbito-cerebral mucormycosis (rocm). despite aggressive measures, including antifungal therapy and repeated endoscopic debridement, he subsequently developed central retinal artery occlusion (crao) and underwent left eye exenteration. keywords: mucormycosis; diabetes mellitus; facial paralysis; retinal artery occlusion cite this article as: mehdi z, bhardwaj n, aggarwal j, kaur n, singh b. facial nerve palsy with total ophthalmoplegia; a novel presentation of fungal invasion. arch acad emerg med. 2021; 9(1): e54, doi: https://doi.org/10.22037/aaem.v9i1.1305. 1. introduction mucormycosis, coined and reclassified by r.d.baker, is an insidious fungal infection caused by ubiquitous mold, mucormycetes, which belongs to family of mucoraceae, order mucorales, class zygomycetes (1, 2). since being reported first in 1885 by german pathologist paltauf, they have increasingly manifested themselves primarily among immunocompromised individuals (1, 2). a 2009 french study reviewing 10-year trends of mucormycosis reported 7.4% annual amplification of such cases (3). diabetes mellitus is the most common predisposing factor, the rest include hematological neoplastic diseases, iron overload, and steroid and deferoxamine therapy (4, 5). the clinical presentation has been broadly divided into five main categories: rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated. rhino-orbitalcerebral mucormycosis (rocm) can be acute or the lesser∗corresponding author: zainab mehdi; area-21, emergency medicine, a block, government medical college and hospital, sector -32 chandigarh, india. email: ir.zainab@gmail.com, tel: +919582432774, orcid: 0000-00028920-3300. known chronic form. acute form spreads aggressively involving nose, sinus, orbit, and other cranial entities within a short period of time, typically manifesting as orbital swelling, headache, ophthalmoplegia, or visual loss (6). facial nerve palsy is a relatively lesser-known and unusual presentation of rocm. it has the potential of being misdiagnosed as a vascular event, causing delayed detection and treatment, while adversely affecting the outcome (7). similarly, central retinal artery occlusion (crao), lower cranial nerves palsy (ix, x cn), and cavernous sinus thrombosis have also been documented as rare presenting symptoms of unilateral rocm (8, 9). here, we report a case of a 38-year-old male with type ii diabetes mellitus who had advanced intracranial and intraorbital mucormycosis. the presence of unilateral lower motor neuron (lmn) type facial palsy and ipsilateral total ophthalmoplegia as presenting features of fungal infection make this case unique. 2. case presentation a 38-year-old male presented to the emergency medicine department of our urban academic tertiary care center with painless left eye swelling for the last seven days. he also comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mehdi et al. 2 plained of progressive limitation of left eye movement with drooping of left eyelid, ultimately causing inability to open left eye over last week. he complained of having double vision while looking sideways. while looking himself in mirror two days ago, he also noticed his mouth deviating towards the right side of his body. he had history of high-grade fever, mostly at night time, in the last fifteen days, which was responsive to oral antipyretics, as well as few episodes of bloody sputum. his wife also noticed his body excessively sweating at night for the last few weeks and his significant weight loss in the last few months. the patient had suffered from diabetes mellitus for the last seven years, non-compliant to orally administered antihyperglycemic agents (oha) treatment. his past medical history revealed having been diagnosed with pulmonary tuberculosis two years back, for which he took regular treatment only for four months. he has smoked (30 pack years), consumes alcoholic beverages four days a week, and occasionally uses opium. there was no history of trauma, involuntary body movements, pus or watery discharge from ear, epistaxis, alteration in sensorium or behavior, dysphagia, or change in voice. no history of any recent surgery was present. the patient was conscious with glasgow coma score (gcs) of e3v4m6, afebrile (temp 99.6 f), blood pressure of 100/80 mmhg, pulse rate of 89/min, and respiratory rate of 22/min, cooperative with physician. neurological examination revealed deviation of angle of mouth to the right side with absent wrinkling of forehead on left side, abnormal grimace with hypoesthesia in distribution of v1, v2 branches of left trigeminal nerve (figure 1). on blowing of mouth air, leak was present from left side. left eye ptosis, immobility, fixed mid-dilated non-reactive pupil and complete loss of accommodation, and loss of left corneal sensation were noted. fundoscopy revealed normal disc and macula. he had bilateral lower and upper limb power of 5/5 with normal reflexes and no other cranial nerve deficit was noted. nasal discharge from left nostril was seen, which was not blood stained. no infraorbital necrosis, ulcer, or perforation of hard palate were present. gag reflex was intact. based on clinical findings, after ruling out possibility of trauma, a differential diagnosis of cerebrovascular accident (cva), intracranial space occupying lesion, tuberculoma or diabetes mellitus-related neuropathy with tuberculosis reactivation were considered. initial non-contrast computed tomography (ct) scan (ncct) of the head revealed left maxillary sinusitis. hematological and biochemical workup done in emergency department revealed anemia, raised total leukocyte count (tlc), and high random blood glucose without ketoacidosis (table 1). cerebrospinal fluid examination was unremarkable. electrocardiogram (ecg) was not suggestive of any abnormality. urine and blood culture were sterile. sample for assessing koh mount of nasal secretion was sent. his sputum was sent for acid fast bacilli (afb) staining as well as fungal evaluation. patient was admitted to the emergency medicine ward and started on intravenous (iv ) antibiotics empirically, and insulin for glycemic control, as further diagnostic evaluations continued. as per local guidelines, his high nasal and oropharyngeal swab were sent for rtpcr for covid-19 which came negative. his chest radiograph revealed fibrotic bands along with cavitary lesion with surrounding consolidation and air crescent sign present in both hemi thoraces (figure 2). contrast-enhanced magnetic resonance imaging (cemri) of brain, orbit, and paranasal sinuses (pns) was done to look for intracranial pathology. it demonstrated acute left maxillary sinusitis with posterolateral wall erosion, prominent left optic nerve sheath, and skull base osteomyelitis with cavernous sinus thrombosis (figure 2). in view of chest x-ray findings, after pulmonary consultation contrast-enhanced ct scan (cect) of chest was performed to aid in decision regarding initiation of anti-tubercular therapy, which suggested tuberculosis reactivation (figure 2). patient’s koh mount of nasal secretion showed non-septate ribbon-like hyphae. based on cumulative results of initial evaluation, a primary diagnosis of invasive rhino-orbito-cerebral mucormycosis with pulmonary tuberculosis reactivation was made. antitubercular treatment (att) was started and ear, nose, throat (ent) review was sought for assessing need for urgent endoscopic debridement, taking in account intra-orbital and intracranial fungal extension causing multiple cranial nerve palsies threatening vision. nasal endoscopic debridement and left orbital decompression were performed the next day. histopathological examination (hpe) of excised tissue revealed broad aseptate hyphae with right angle branching invading both nerves and vessel wall, confirming diagnosis of invasive mucormycosis (figure 2). patient was started on amphotericin b, optimal anticoagulation, and insulin therapy for optimization of glycemic control. his biochemistry was regularly monitored for any nephrotoxicity, hematotoxicity, and other infusion-related adverse effects. a repeat endoscopic debridement was performed after a period of seven days. meanwhile, serial fundoscopy was performed by ophthalmologist to look for possible optic nerve involvement, any optic disc changes, papilledema, or decrease in visual acuity and field. a week after the second debridement and thirteen days of amphotericin b cumulative dose 1425 milligrams, patient complained of severe pain in left side of face, predominant in the orbital region with increased swelling on waking up from sleep. fundus examination revealed a cherry red spot, optic disc edema with complete retinal opacification, suggesting central retinal artery occlusion in left eye. patient was started on topical timolol 0.5% and systemic acetazolamide alongthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e54 side intermittent digital ocular massage with the aim of reducing intraocular pressure. he did not respond to the above measures and decision for left eye exenteration alongside repeat decompression and debridement was made. postexenteration monitoring for involvement of right eye and other signs of raised intraocular and intracranial pressures continued alongside antifungal therapy. his condition remained satisfactory and gradual improvement followed. his right eye vision remained unaltered and serial fundoscopy did not reveal any alarming features. optimal glycemic control was achieved with insulin therapy. he was ultimately discharged home after 48 days of hospital stay in a stable state with residual left facial nerve palsy, written advice to follow up for dressing, ocular prosthesis, and further treatment optimization. 3. discussion mucormycosis, a deadly fungal infection by mucorales, nearly invariably involving immunocompromised patients, especially diabetics, can disseminate to paranasal sinuses, retro orbital regions, and brain. its ability to extensively and uniformly invade vessels facilitates hematogenous spread to various areas leading to vessel thrombosis and tissue necrosis in multiple organs (10). factors that render diabetics more prone to fungal invasion include pre-existing nerve ischemia and injury, abnormal endoneurial and epineural vessels, resistant arteries, reduced chemotaxis and phagocytic efficiency, and favorable acidic and high-sugar environment helping hyphae production (7, 11). pterygopalatine fossa plays a key role in involvement of facial nerve and retro global area. its numerous vascular and neural connections facilitate cranial invasion and lower cranial nerve palsies (7). our patient had fungal skull base osteomyelitis, which may have facilitated facial nerve invasion via pterygopalatine fossa, cavernous sinus thrombosis causing ipsilateral involvement of third, fourth and sixth cranial nerves manifesting as total ophthalmoplegia and sensory loss in distribution of v1 and v3 divisions of the fifth cranial nerve. prognosis of mucormycosis with intracranial and intraorbital extension is disastrous and usually fatal. amalgamation of surgical debridement and amphotericin b has improved patient survival to 85% from 24% in those untreated (12). our patient was managed with early and multiplestaged endoscopic debridement. he received a total dose of 4125 milligrams of amphotericin b. due to advanced fungal invasion of left optic nerve and subsequent thrombosis of ophthalmic artery, his left eye could not be salvaged. knowing that unilateral facial nerve palsy can be a presenting feature of intracranial spread of fungal infection and considering it in the initial workup of all immunocompromised patients presenting with peripheral neuropathy can help early cessation of disease advancement and salvage of organs. multiple cranial nerve palsies in an immunocompromised patient without history of trauma should alarm emergency physician of possible intracranial fungal infection. it is of outmost importance to assess koh mount of nasal secretions, keep a low threshold for cemri of brain, orbit, and pns and start antifungal treatment as early as possible. long duration of amphotericin therapy demands close monitoring and intervention for any drug side effects. continual monitoring for any new sign and symptom is recommended as patients tend to develop other complications while on treatment, like crao in our case. 4. conclusion mucormycosis infection in immunocompromised individuals can diverge considerably: from being a simple acute fungal sinusitis to deadly orbital and cranial extension. therefore, an approach based on early suspicion, detection, and intervention, resulting in favorable outcome and preventing complications, is commendable. 5. declarations 5.1. ethical considerations and patient’s consent the authors certify that they have obtained all appropriate patient consent forms. in the form, the patient has given his consent for his images and other clinical information to be reported in the journal. the patient understands that name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed. 5.2. authors’ contributions all the authors have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. all the authors have been involved in drafting the manuscript or revising it critically for important intellectual content and have given final approval of the version to be published. each author has participated sufficiently in the work to take public responsibility for appropriate portions of the content. the corresponding author takes responsibility for the article during the submission and review process. dr zainab mehdi: concept, design, intellectual content, literature search, data acquisition, manuscript preparation, editing, and review dr nidhi bhardwaj: concept, design, intellectual content, literature search, editing, and review dr jyoti aggarwal: literature search, manuscript preparation, data acquisition, manuscript editing and review dr. narinder kaur: literature search, clinical studies, data this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mehdi et al. 4 acquisition, manuscript preparation, editing, and review dr. brijdeep singh: literature search, clinical studies, data acquisition, manuscript preparation, editing, and review 5.3. funding and support none. 5.4. conflicts of interest none declared. 5.5. acknowledgment none. references 1. mohammadi r, nazeri m, sayedayn sma, ehteram h. a successful treatment of rhinocerebral mucormycosis due to rhizopus oryzae. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2014;19(1):72. 2. roden mm, zaoutis te, buchanan wl, knudsen ta, sarkisova ta, schaufele rl, et al. epidemiology and outcome of zygomycosis: a review of 929 reported cases. clinical infectious diseases. 2005;41(5):634-53. 3. bitar d, van cauteren d, lanternier f, dannaoui e, che d, dromer f, et al. increasing incidence of zygomycosis (mucormycosis), france, 1997–2006. emerging infectious diseases. 2009;15(9):1395. 4. rees jr, pinner rw, hajjeh ra, brandt me, reingold al. the epidemiological features of invasive mycotic infections in the san francisco bay area, 1992–1993: results of population-based laboratory active surveillance. clinical infectious diseases. 1998;27(5):1138-47. 5. narayanan s, panarkandy g, subramaniam g, radhakrishnan c, thulaseedharan n, manikath n, et al. the “black evil” affecting patients with diabetes: a case of rhino orbito cerebral mucormycosis causing garcin syndrome. infection and drug resistance. 2017;10:103. 6. sachdeva k. rhino-oculo cerebral mucormycosis with multiple cranial nerve palsy in diabetic patient: review of six cases. indian journal of otolaryngology and head & neck surgery. 2013;65(4):375-9. 7. mane r, patil b, mohite a, mohanty r. facial nerve palsy: an unusual presentation in patients with rhino cerebral mucormycosis. indian journal of otolaryngology and head & neck surgery. 2019;71(3):2110-3. 8. idris f, sow yl, jamaluddin js, ong fm, ibrahim s. acute invasive fungal sinusitis (mucormycosis): challenging presentation with cavernous sinus thrombosis and multiple cranial nerves palsy. international medical journal. 2019;26(6). 9. bawankar p, lahane s, pathak p, gonde p, singh a. central retinal artery occlusion as the presenting manifestation of invasive rhino-orbital-cerebral mucormycosis. taiwan journal of ophthalmology. 2020;10(1):62. 10. spellberg b, edwards jr j, ibrahim a. novel perspectives on mucormycosis: pathophysiology, presentation, and management. clinical microbiology reviews. 2005;18(3):556-69. 11. riga m, kefalidis g, danielides v. the role of diabetes mellitus in the clinical presentation and prognosis of bell palsy. the journal of the american board of family medicine. 2012;25(6):819-26. 12. gelston cd, durairaj vd, simoes ea. rhino-orbital mucormycosis causing cavernous sinus and internal carotid thrombosis treated with posaconazole. archives of ophthalmology. 2007;125(6):848-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e54 figure 1: (a) left facial droop and deviation of mouth to right side; (b) left sided absence of forehead wrinkling and left sided ptosis; (c) inability to open eye and absent eyeball movement on left side upon being asked to look up. figure 2: (a) chest x-ray posteroanterior (pa) view showing right upper and lower zone cavitary lesions with radiopacity in dependant parts and air-crescent sign along the non-dependant parts. multiple alveolar infiltrates and linear strands are seen in left upper and middle zones; (b) axial t1-weighted contrast-enhanced mri at the level of base of skull showing enhancement of basisphenoid, clivus, and basiocciput. contrast enhancement was extending to left sided retroantral fat and posterolateral wall of left maxillary sinus and contents of left infratemporal fossa. left maxillary sinus shows mucosal thickening along the posteromedial wall, air fluid level and hyperdensity along the medial wall. all these findings are suggestive of invasive fungal sinusitis; (c) axial t1-weighted contrast-enhanced mri at the level of cavernous sinus and orbits showing post contrast enhancement of left optic canal and optic nerve. a small filling defect is noted in left cavernous sinus as well as outward bulge of the lateral wall, which indicates thrombosis; (d) ct chest showing cavitary lesion in right middle lobe with air crescent sign along the non-dependant part and ball-like soft tissue along the dependant part of cavity. adjacent lung parenchyma postero-laterally shows consolidation and thickening of abutting right oblique fissure; (e) haematoxylin and eosin (h&e) stain (20x10) fungal profiles can be seen invading vessel wall accompanied by dense inflammatory cell infiltrate comprising neutrophils, lymphocyte, and few scattered eosinophils and plasma cells. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mehdi et al. 6 table 1: results of laboratory investigations performed during the hospital stay variables day1 day7 day14 day21 day28 day32 day40 hemoglobin (g/dl) 10.7 9.8 10.2 11.7 12 11.6 12.1 leukocyte count(109cells/l) 12.3 13.3 16.9 11.1 9.8 6.1 6.3 polymorphs (%) 79.1 60 66 67 70 71 68 lymphocytes (%) 8.7 8.5 8.2 7.3 8.1 6.8 7.1 eosinophils (%) 3.2 3.2 3.1 2.9 2.9 3 3.3 basophils (%) 1.6 1.4 1.2 1.6 1.1 1.5 1.4 monocytes (%) 0.4 0.6 0.6 0.3 0.8 0.6 0.4 platelet count (lac/mm3) 475 471 506 696 423 413 415 esr* (mm/hour) 12 10 10 8 total serum bilirubin (mg/dl) 0.1 1.3 0.7 conjugated bilirubin (mg/dl) .3 .4 .2 alkaline phosphatase (u/l) 70 69 70 101 72 68 66 ast (u/l) 18 40 130 135 118 98 45 alt (u/l) 27 47 143 147 125 103 53 total protein 6.4 7.6 5.7 5.9 albumin 3.5 2.8 3.1 3.0 serum sodium (meq/l) 136 137 125 129 136 139 141 serum potassium (meq/l) 4.7 4.1 3.6 3.8 4.1 4.5 4.4 chloride (meq/l) blood urea (mg/dl) 21 23 37 32 28 20 16 serum creatinine (mg/dl) 0.6 0.7 0.9 0.5 0.6 0.6 0.7 calcium (mg/dl) 9.1 8.9 8.2 8.3 8.7 9.1 9.3 magnesium (mg/dl) 2.7 2.2 1.9 1.8 1.9 2.7 3 phosphorus (mg/dl) 2.9 3.8 2.9 2.6 2.7 2.8 2.9 fbs (mg/dl) 286 228 237 195 121 201 198 ph* 7.34 7.34 7.23 7.24 7.34 7.35 7.41 pao2 88 89 88 87 88 88 88 paco2 44 36 38 42 43 42 45 hco3 23 28 26 24 24 22 24 spo2 (%) 89 94 93 95 96 94 93 lactate 1.4 1.6 1.7 .9 .9 1.0 .9 urine ketone nil nil hba1c 13 *: arterial blood gas analysis. ast: aspartate aminotransferase, alt: alanine transaminase, ldh: lactate dehydrogenase, spo2: peripheral oxygen saturation, esr: erythrocyte sedimentation rate, fbs: fasting blood sugar. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2017; 5 (1): e19 or i g i n a l re s e a rc h screening characteristics of bedside ultrasonography in confirming endotracheal tube placement; a diagnostic accuracy study hamid zamani moghadam1, mohamad davood sharifi1∗, hasan rajabi1, mojtaba mousavi bazazi2, ali alamdaran3, niazmohammad jafari1, seyed amir masoud hashemian1, morteza talebi deloei1 1. department of emergency medicine, mashhad university of medical sciences, mashhad, iran. 2. department of social medicine, school of medicine, mashhad university of medical sciences, mashhad, iran. 3. department of radiology, mashhad university of medical sciences, mashhad, iran. received: april 2016; accepted: august 2016; published online: 9 january 2017 abstract: introduction: confirmation of proper endotracheal tube placement is one of the most important and lifesaving issues of tracheal intubation. the present study was aimed to evaluate the accuracy of tracheal ultrasonography by emergency residents in this regard. methods: this was a prospective, cross sectional study for evaluating the diagnostic accuracy of ultrasonography in endotracheal tube placement confirmation compared to a combination of 4 clinical confirmation methods of chest and epigastric auscultation, direct laryngoscopy, aspiration of the tube, and pulse oximetry (as reference test). results: 150 patients with the mean age of 58.52 ± 1.73 years were included (56.6% male). sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio of tracheal ultrasonography in endotracheal tube confirmation were 96 (95% ci: 92-99), 88 (95% ci: 62-97), 98 (95% ci: 94-99), 78 (95% ci: 53-93), 64 (95% ci: 16-255), and 0.2 (95% ci: 0.10.6), respectively. conclusion: the present study showed that tracheal ultrasonography by trained emergency medicine residents had excellent sensitivity (>90%) and good specificity (80-90) for confirming endotracheal tube placement. therefore, it seems that ultrasonography is a proper screening tool in determining endotracheal tube placement. keywords: ultrasonography; intubation, intratracheal; airway management; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: zamani moghadam h, sharifi m, rajabi h, mousavi bazaz m, alamdaran a, jafari n, hashemian s-a, talebi deloei m. screening characteristics of bedside ultrasonography in confirming endotracheal tube placement; a diagnostic accuracy study; a clinical audit. emergency. 2017; 5 (1): e19. 1. introduction in the advanced cardiac life support (acls 2010) guidelines, one of the first essential steps in resuscitation is to have a confident airway so that ventilation can be continued properly (1). there are different ways to provide a proper airway for a patient who needs help for breathing. in some situations, like cardiac arrest, respiratory failure and loss of consciousness, only a good intubation can save their life (2). on the other hand, misplacement of the tracheal tube is a ∗corresponding author: mohamad davood sharifi; emergency department, imam reza hospital, bahar avenue, khorasan razavi, mashhad, iran. tel: 09151156758 email: sharifimd@mums.ac.ir life-threatening situation, which leads to a high mortality and morbidity rate. the incidence of esophageal intubation is reported to be about 6-16% in emergency settings (3, 4). the complications of the tube being placed in esophagus are increasing likelihood of gastric content aspiration into the respiratory system, shortness of breath accompanied by stomach volume expansion with the excess volume of air input, and the most important, losing the golden time to intubate, and subsequent hypoxia of basic organs (5). according to this concept, early detection of misplacement of tracheal tube is important and can be lifesaving. the clinicians have suggested many different ways to confirm the placement of the tube including traditional methods like direct laryngoscopy to see vocal cords, observation of chest movement, epigastric auscultation, noting the water steam this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. zamani-moghaddam et al. 2 in the tube, and feeling air exiting from the end of the tube after inflation (6). each of these has limitations that make them not reliable enough to be used as a gold standard for proper placing of the tube in emergency settings, confidently. the second group of methods to confirm the tube placement is para clinical modalities like chest x-ray, pulse–oximetry, capnography, and ultrasonography. some researchers have introduced quantitative capnography as the most sensitive tool to distinguish tracheal tube placement (7). according to the american heart association (aha 2010) guidelines, quantitative wave waveform capnography is the most reliable method for confirming the tracheal tube placement (1). but, this diagnostic method is not available in every emergency department. in addition, like other methods, it gives some false negative and positive results (8). today, ultrasonography is a common tool in emergency physicians’ hand. so it can be proposed as a fast, low–cost and portable method to confirm proper tube placement. many clinical studies have been carried out to evaluate the accuracy of ultrasonography in correct placement of endotracheal tube (9-21). some of these studies are cadaveric ones, but most of them are done on patients in emergency settings. however, information regarding feasibility and accuracy of this method particularly when performed by emergency residents is lacking in iran, since emergency medicine is a young specialty in this country. the present study was aimed to determinate the accuracy of ultrasonography by emergency residents for confirmation of correct tracheal tube placement in real time. 2. methods 2.1. study design and setting this was a prospective, cross sectional study, which was performed in the emergency department (ed) of imam reza hospital, mashhad, iran, between march and september 2014, aiming to evaluate the diagnostic accuracy of ultrasonography in endotracheal tube placement confirmation. the study protocol was approved by the committee on medical ethics in research in mashhad university of medical sciences. all subjects were chosen from ed of imam reza hospital, which is a tertiary teaching and research hospital. the researchers adhered to the principles of helsinki declaration. 2.2. participants patients who needed a secure airway due to having no spontaneous respiratory attempt were included in the study using convenience sampling method. these individuals were either intubated primarily on arrival or secondarily after a period of staying in ed. the inclusion criteria involved all the indications of tracheal intubation like failure of ventilation figure 1: tracheal ultrasonography. or oxygenation, failure to maintain or protect the airway, and the patient’s anticipated clinical course and likelihood of deterioration. patients were excluded if they had severe neck trauma, neck masses, a history of any neck operations, and were under the age of 18 years. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e19 2.3. measurement the intubation process was performed by senior emergency medicine residents. then another senior emergency medicine resident, which was unaware of the tube placement, checked the tube using ultrasonography (honda hf2100, japan) with a 5.0-7.5 mhz linear transducer. these residents were educated in ultrasonography techniques and how to use it for confirmation of the tracheal tube placement. simultaneously, another resident confirmed the tube placement using four methods: chest and epigastric auscultation, direct laryngoscopy, aspiration of the tube, and pulse oximetry. if three of these methods showed that the tube is in the trachea, endotracheal intubation was confirmed. these 4 methods together were considered as the reference test and ultrasonography (index test) was compared with their result. every time intubation and confirmation of the placement were done, an attending emergency physician had been supervising the whole process. figure 1 shows the location of probe as well as ultrasonographic views of correct and incorrect tube placement. the probe was placed transversely on the neck in lateral position and in front of cricoid cartilage (approximate to sixth cervical vertebra or c6). in a normal anatomy of neck, trachea is seen as a non-compressible circular structure, which is hollow with reverberation. laterally, the esophagus is seen with smaller size and comprisable lumen, which makes the image of a collapsed donut. however, when the tube is in the esophagus, we can see two circular structures together. the tube in esophagus makes an image of two parallel lines named “goose sign” (figure 1). 2.4. statistical analysis previous studies showed that sensitivity of ultrasound in determining endotracheal tube placement was 100% (12). sample size was calculated to be 131 patients based on a 95% confidence interval, a desired precision of 0.01 and prevalence of 30%. all statistical analyses were performed using spss statistical software version 20.0. evaluating the screening performance characteristics of ultrasonography by residents in conformation of correct tracheal intubation, sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr), negative likelihood ratio (nlr) as well as area under the receiver operating characteristics (roc) curve with 95% confidence interval (ci) were calculated. 3. results: 150 patients with the mean age of 58.52 ± 1.73 years were studied (56% male). the most frequent indications of intubation were loss of consciousness in 63 (42%) cases, respiratory failure in 52 (34.7%), cardiac arrest in 15 (10%), and prophylactic in 20 (13.3%) patients. based on the findings of the reference test, placement of tube was correct in 133 (88.7%) cases (tracheal intubation) and incorrect in 17 (11.3%) (esophageal intubation). emergency resident correctly reported 129 (97%) cases of tracheal intubation (number of true positive) and 15 (88.2%) cases of esophageal ones (number of true negative) using ultrasonography. the overall accuracy of ultrasonography by emergency resident in confirmation of tracheal intubation based on the area under the roc curve was 92 (83-100). the sensitivity, specificity, ppv and npv, and plr and nlr of emergency resident performance of ultrasonography, compared to the combination of 4 clinical methods as the reference test, were 96 (95% ci: 9299), 88 (95% ci: 62-97), 98 (95% ci: 94-99), 78 (95% ci: 53-93), 64 (95% ci: 16-255), and 0.2 (95% ci: 0.1-0.6), respectively. screening characteristics of ultrasonography by emergency resident for detecting correct tracheal intubation based on different causes of intubation are shown in table 1. 4. discussion: the present study showed excellent sensitivity and good specificity of ultrasonography by emergency resident in confirming endotracheal tube placement. ultrasonography is available in almost all emergency departments. unlike other methods of proper tube placement confirmation, ultrasonography can distinguish the place of tube before bagvalve-mask ventilation, so it can prevent ventilation of stomach and its complications like aspiration. in addition, using ultrasonography does not interrupt the cpr process like other methods do. therefore, it seems that ultrasonography is a proper screening tool in determining endotracheal tube placement. many other researchers had been reaching the same results in their studies and concluded that tracheal ultrasound can be a reliable method for assessing placement of tracheal tube in emergency settings. for example, ma et al. (9) evaluated correctness of tracheal intubation in two phases, dynamic (when intubation was proceeded) and static (after the intubation procedure), by trans-tracheal ultrasonography. they deducted a sensitivity of 97% and specificity of 100% in dynamic phase of intubation but a lower specificity was detected in the static phase (57%). in another study, chou et al. (14) studied 112 patients. among them, 15.2% of cases had esophageal intubations and ultrasound could detect a high rate of these displacements by an accuracy of 98.2%, and the sensitivity and specificity of 98.9% and 94.1%, respectively. there are some other researches, which have found 100% sensitivity and specificity for ultrasonography in determining tube placement, but the main limitation of most of these studies is having a small sample size and therefore, they may not show the real characteristics of a large number of people referring to a tertiary hospital in a big city. for example, werner et al. (11) assessed only 33 patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. zamani-moghaddam et al. 4 table 1: screening characteristics of ultrasonography in determining endotracheal tube placement based on cause of intubation values loss of consciousness respiratory failure cardiac arrest other causes sensitivity 98.2 (98.2-99.9) 97.9 (87.5-99.9) 84.6 (53.7-97.3) 100 (75.9-100) specificity 85.7 (42.0-99.2) 100 (39.6-100) 100 (19.9-100) 75.0 (21.9-98.7) accuracy 96.8 (92.5-100) 98.0 (94.3-100) 86.7 (69.5-100) 95.0 (85.4-100) ppv 98.2 (98.2-99.9) 100 (90.6-100) 100 (67.8-100) 94.1 (96.2-99.7) npv 85.7 (42.0-99.2) 80.0 (29.9-99.0) 50.0 (9.2-90.8) 100 (30.3-100) plr 6.9 (1.1-42.2) na na 4.0 (73.3-21.8) nlr 0.02 (0.002-0.2) 0.02 (0.003-0.1) 0.15 (0.04-0.6) 0.0 (0.0-0.0) auc 0.92 (0.82-0.97) 0.99 (0.90-1.0) 0.92 (0.68-1.0) 0.88 (0.68-0.99) ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; auc: area under the roc curve; na: not applicable due to the calculation cannot be performed because the values include one or more instances of zero. on the other hand, there are few studies challenging the diagnostic value of ultrasonography by emergency medicine residents for evaluation of tube placement. for instance, sim et al. (13) reported a specificity of 55.6% for ultrasonography. there are two recent review articles on this topic. the first one included 12 human studies and calculated a sensitivity of 0.93 and specificity of 0.97 with the positive and negative likelihood ratios of 26.98 and 0.08, respectively (22). the other meta–analysis reviewed 11 articles with 962 intubations in total. they calculated the sensitivity and specificity of 98% for ultrasonography as the confirmation method of tracheal tube placement (23). 5. limitations: our study had some limitations. we didn’t estimate the time needed for each method, an important factor in selecting a proper method especially in emergent situations. however, studies have shown that the time needed for ultrasonography is significantly lower than capnography (23, 24). therefore, it is safe to say evaluation of proper placement of tracheal tube using ultrasonography is faster than capnography. another limitation of this study was not using capnography as the reference test. although we tried to reduce performing bias to a minimum by using 4 methods of direct laryngoscopy, clinical auscultation, aspiration and pulse oximetry, misclassification of patients might have affected the accuracy reported in the present study. in addition, convenience sampling in this study is a possible source of publication bias. 6. conclusion: the present study showed that tracheal ultrasonography by trained emergency medicine residents had excellent sensitivity (>90%) and good specificity (80-90) for confirming endotracheal tube placement. therefore, it seems that ultrasonography is a proper screening tool in determining endotracheal tube placement. 7. appendix 7.1. acknowledgements this article has been derived from dr. hasan rajabi’s student thesis to receive his specialist degree in emergency medicine from mashhad university of medical sciences. authors would like to acknowledge all the emergency department staff of imam reza hospital. 7.2. authors contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the 4 criteria of authorship recommended by the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. neumar rw, otto cw, link ms, kronick sl, shuster m, callaway cw, et al. part 8: adult advanced cardiovascular life support 2010 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2010;122(18 suppl 3):s729s67. 2. schwartz de, matthay ma, cohen nh. death and other complications of emergency airway management in critically ill adults a prospective investigation of 297 tracheal intubations. the journal of the american society of anesthesiologists. 1995;82(2):367-76. 3. mort tc. unplanned tracheal extubation outside the operating room: a quality improvement audit of hemodynamic and tracheal airway complications associated this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e19 with emergency tracheal reintubation. anesthesia & analgesia. 1998;86(6):1171-6. 4. grmec s. comparison of three different methods to confirm tracheal tube placement in emergency intubation. intensive care medicine. 2002;28(6):701-4. 5. mort tc. emergency tracheal intubation: complications associated with repeated laryngoscopic attempts. anesthesia & analgesia. 2004;99(2):607-13. 6. roberts jr, hedges jr. roberts and hedges’ clinical procedures in emergency medicine: elsevier health sciences; 2013. 7. foutch rg, magelssen md, macmillan jg. the esophageal detector device: a rapid and accurate method for assessing tracheal versus esophageal intubation in a porcine model. annals of emergency medicine. 1992;21(9):1073-6. 8. garnett ar, ornato jp, gonzalez er, johnson eb. end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. jama. 1987;257(4):512-5. 9. ma g, davis dp, schmitt j, vilke gm, chan tc, hayden sr. the sensitivity and specificity of transcricothyroid ultrasonography to confirm endotracheal tube placement in a cadaver model. the journal of emergency medicine. 2007;32(4):405-7. 10. chou h-c, tseng w-p, wang c-h, ma mh-m, wang h-p, huang p-c, et al. tracheal rapid ultrasound exam (true) for confirming endotracheal tube placement during emergency intubation. resuscitation. 2011;82(10):127984. 11. werner sl, smith ce, goldstein jr, jones ra, cydulka rk. pilot study to evaluate the accuracy of ultrasonography in confirming endotracheal tube placement. annals of emergency medicine. 2007;49(1):75-80. 12. muslu b, sert h, kaya a, demircioglu ri, gozdemir m, usta b, et al. use of sonography for rapid identification of esophageal and tracheal intubations in adult patients. journal of ultrasound in medicine. 2011;30(5):671-6. 13. sim s-s, lien w-c, chou h-c, chong k-m, liu s-h, wang c-h, et al. ultrasonographic lung sliding sign in confirming proper endotracheal intubation during emergency intubation. resuscitation. 2012;83(3):307-12. 14. chou h-c, chong k-m, sim s-s, ma mh-m, liu sh, chen n-c, et al. real-time tracheal ultrasonography for confirmation of endotracheal tube placement during cardiopulmonary resuscitation. resuscitation. 2013;84(12):1708-12. 15. tessaro mo, salant ep, arroyo ac, haines le, dickman e. tracheal rapid ultrasound saline test (trust) for confirming correct endotracheal tube depth in children. resuscitation. 2015;89:8-12. 16. zadel s, strnad m, prosen g, mekis d. point of care ultrasound for orotracheal tube placement assessment in out-of hospital setting. resuscitation. 2015;87:1-6. 17. milling tj, jones m, khan t, tad-y d, melniker la, bove j, et al. transtracheal 2-d ultrasound for identification of esophageal intubation. the journal of emergency medicine. 2007;32(4):409-14. 18. quintela pa, erroz io, matilla mm, blanco sr, zubillaga dm, santos lr. usefulness of bedside ultrasound compared to capnography and x-ray for tracheal intubation. anales de pediatrãŋa (english edition). 2014;81(5):283-8. 19. gottlieb m, bailitz jm, christian e, russell fm, ehrman rr, khishfe b, et al. accuracy of a novel ultrasound technique for confirmation of endotracheal intubation by expert and novice emergency physicians. western journal of emergency medicine. 2014;15(7):834. 20. budhram g, murman d, lutfy l, sullivan a. sonographic confirmation of intubation comparison of 3 methods in a pig model. journal of ultrasound in medicine. 2014;33(11):1925-9. 21. sun j-t, chou h-c, sim s-s, chong k-m, ma mh-m, wang h-p, et al. ultrasonography for proper endotracheal tube placement confirmation in out-of-hospital cardiac arrest patients: two-center experience. journal of medical ultrasound. 2014;22(2):83-7. 22. chou eh, dickman e, tsou p-y, tessaro m, tsai y-m, ma mh-m, et al. ultrasonography for confirmation of endotracheal tube placement: a systematic review and metaanalysis. resuscitation. 2015;90:97-103. 23. das sk, choupoo ns, haldar r, lahkar a. transtracheal ultrasound for verification of endotracheal tube placement: a systematic review and meta-analysis. canadian journal of anesthesia/journal canadien d’anesthesie. 2015;62(4):413-23. 24. pfeiffer p, rudolph s, borglum j, isbye d. temporal comparison of ultrasound vs. auscultation and capnography in verification of endotracheal tube placement. acta anaesthesiologica scandinavica. 2011;55(10):1190-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references emergency. 2017; 5 (1): e25 or i g i n a l re s e a rc h the effect of magnesium sulfate on renal colic pain relief; a randomized clinical trial abolfazl jokar1, ali cyrus1, maryam babaei1, majid taheri2, amir almasi-hashiani3, ezatollah behzadinia1 ∗, arash yazdanbakhsh1 1. department of emergency medicine, arak university of medical sciences, arak, iran. 2. medical ethics and law research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of epidemiology and reproductive health, reproductive epidemiology research center, royan institute for reproductive biomedicine, acecr, tehran, iran. received: june 2016; accepted: august 2016; published online: 10 january 2017 abstract: introduction: renal colic can be managed by preventing the contraction movements of ureter muscles. by reducing the acetylcholine in the nerve terminals, magnesium sulfate could be effective in this regard. the aim of this study is to investigate the effect of magnesium sulfate on acute renal colic pain relief. methods: the present study was a double-blind clinical trial in which the patients suffering from acute renal colic were randomly divided into 2 groups of who were received standard protocol (intravenous infusion of 0.1 mg/kg morphine sulfate, 30 mg of ketorolac, and 100 ml normal saline as placebo/15 minutes) or standard protocol plus 15 mg/kg of intravenous magnesium sulfate 50%/100 ml normal saline/15 minutes. severity of patients’ pain was measured by visual analogue scale (vas) at baseline, and 30 and 60 minutes after infusion. the collected data were analyzed using stata statistical software. results: 100 cases were randomly allocated to intervention or control group. the two groups were similar in baseline pain score and demographic characteristics. at 30 and 60 minutes, mean pain score was less in the intervention groupcompare to the control group. moreover, the difference between the two groups was statistically significant regarding the additional amount of morphine, suggesting that the intervention group needed less additional morphine than the control group. conclusion: the results of this study indicated that magnesium sulfate can be used as an adjunct drug in treatment of patients suffering from renal colic. it can reduce the pain and diminish the need for additional doses of morphine sulfate without disturbing hemodynamic measures. however, the amounts of these effects are not clinically significant. keywords: renal colic; magnesium sulfate; therapeutics; emergency department; pain management © copyright (2017) shahid beheshti university of medical sciences cite this article as: jokar a, cyrus a, babaei m, taheri m, almasi-hashiani a, behzadinia e, yazdanbakhsh a. the effect of magnesium sulfate on renal colic pain relief; a randomized clinical trial . emergency. 2017; 5 (1): e25. 1. introduction urinary tract stone is a common urological disease which is often symptomized through twinges localized to the sides or a radicular pain towards groins and genitalia, which is referred to as renal colic (1). due to the obstruction of urine flow and thereby increased ureteral wall traction, renal colic is formed above the point of obstruction. this increased pressure surges the production and local release of ∗corresponding author: ezatollah behzadinia; department of emergency medicine, vali-asr hospital, arak university of medical sciences, arak, iran. email: ezzatullah_bezadinia@yahoo.com; tel: 08632222003 prostaglandins which brings about dilation of blood vessels and diuresis, resulting in a further increase in the pressure inside the kidney. high levels of prostaglandins, also play a role in development of edema around the stones (2). in addition, long isotonic contractions above the point of obstruction increase the production of lactic acid, contributing to slow type a and fast type c nerve fibers’ stimulation and introduction of more pain (3). a wide variety of medications are available to treat the pain associated with acute renal colic, each of which affect different parts of the mechanisms causing the pain. for the time being, opioids and nonsteroidal anti-inflammatories drugs (nsaids) are the main drugs in treatment of renal colic. opioids are cheap and measurable drugs; nevertheless, they are addictive and may this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jokar et al. 2 have side effects such as nausea, vomiting, constipation and drowsiness. in higher doses, they can even cause respiratory depression. furthermore, opioids have no effect on the cause of pain while they may have contractile effects on the ureteral tone (4).nsaid, on the other hand, having a direct effect on prostaglandins release, can bring about pain relief through reducing renal pressure and diuresis. they may also reduce the edema of ureter around the stones (2). despite all these advantages, however, these drugs may induce some secondary regulatory responses in the kidney leading to some obstructions (5). considering that renal colic can be caused by peristalsis movements above the point of obstruction (1), it is hypothesized that it is possible to control the patients’ pain by preventing the contraction movements in the ureters. by the same token, tocolytic drugs su as magnesium sulfate can be effective in this regard. it prevents calcium from entering the smooth muscle cell membrane, activates adenylate cyclase and cyclic amp, and increases the uptake of calcium by sarcoplasmic network (6). moreover, reducing acetylcholine in the nerve terminals, magnesium sulfate can also decrease muscle contractions (5). based on abovementioned facts, the aim of the present study is to investigate the effect of magnesium sulfate on acute renal colic pain relief. 2. methods 2.1. study design and setting this randomized double-blind clinical trial was designed to investigate the effect of intravenous magnesium sulfate in pain relief of patients presenting to emergency department (ed) following renal colic. 2.2. ethical consideration before being included in the study, all the patients were provided with proper explanation about the study and they signed the informed consent for being included. they were free to decline to participate and to withdraw from the study. all the research group members were required to comply with all the provisions of the declaration of helsinki and arak university of medical sciences research ethics. in addition, this project has been approved by arak university of medical sciences ethics committee (code: arakmu.ac.1394.44). this study is registered on iranian registry of clinical trias with theregistration number: irct2016020223552n6. 2.3. participants patients suffering from acute renal colic admitted to the ed of vali-asr hospital, arak, iran, comprised the target population of this study. the cases were enrolled using convenient sampling, considering some inclusion and exclusion criteria. inclusion criteria were as follows: being clinically diagnosed as renal colic, being between 18 to 55 years old, and having a pain severity > 5 based on visual analogue scale (vas) (7). exclusion criteria were as follows: a history of seizure; any heart, liver, kidney or metabolic disease; fever (oral temperature > 38 celsius), systolic blood pressure less than 90 mm hg, pregnancy, acute abdomen, paregoric drug consumption 3 hours before presenting to ed, history of addiction or drug allergy, and having taken calcium channel blockers. renal colic was clinically defined through diagnosis of such practical benchmarks as twinges localized to the sides or radicular pain towards groins, lower abdomen and testicles with probable associated symptoms like nausea, vomiting, sweating, pallor, dysuria, frequent urination, urgency of urination, and blood in the urine. suspected cases of acute coronary syndrome were ruled out with electrocardiography. 2.4. randomization and sequence generation patients were randomly allocated to two groups using a balanced block randomization technique. to do that, they were divided into blocks of 6. allocation of the subjects into two groups was done with the help of an online application called “sealed envelope” (8). in this study, as a result of using balanced block randomization and allocating unique codes to each individual, “allocation concealment” was carried out. owing to random allocation, distribution of potential confounding variables is considered to be identical in the two groups and their confounding role is controlled. 2.5. implementation random allocation sequence was performed by our methodologist colleague through sealed envelope website. eligibility assessment of the patients and their allocation was conducted by the emergency resident under the supervision of the main person responsible for the project. 2.6. blinding in this study, the patients and the one who was responsible for measuring the desired outcomes in different groups were both blind to group allocation of patients. 2.7. intervention an emergency medicine specialist randomly divided the patients into 2 groups. in the first group, the patients were treated with the standard protocol of 0.1 mg/kg of intravenous morphine sulfate, 30 mg of intravenous ketorolac, and 100 ml intravenous normal saline, as placebo, within 15 minutes. in the second group, along with the standard protocol, 15 mg/kg of intravenous magnesium sulfate 50% in 100 ml normal saline was additionally infused within 15 minutes (9). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e25 table 1: comparison of baseline characteristics between intervention (magnesium sulfate) and control (standard protocol) groups variables study groups p value intervention control sex (male) 30 (60%) 29 (58%) 0.839 age (year) 33.64±8.61 35.16±8.97 0.389 weight (kg) 73.72±6.25 74.84±8.21 0.444 height (20) 172.24±5.47 171.36±6.40 0.462 systolic bp (mmhg) 137.56±7.93 137.36±10.61 0.915 diastolic bp(mmhg) 81.88±6.83 82.16±6.68 0.836 pain severity (7) 9.12±0.77 9.04±0.83 0.619 pulse rate (1/minute) 96.12±4.69 96.08±3.42 0.961 respiratory rate(1/minute) 17.24±1.34 17.04±1.41 0.470 o2 saturation (%) 93.88±1.79 93.72±1.77 0.654 temperature (celsius) 37.14±0.30 37.01±0.16 0.010 morphine dose (mg) 6.88±0.71 6.96±0.96 0.639 data were presented as mean ± standard deviation or number and percentage. bp: blood pressure, vas: visual analogue scale. table 2: means hemodynamic measures and pain severity at different times for intervention (magnesium sulfate) and control (standard protocol) groups variables study groups p value intervention control systolic blood pressure (mmhg) baseline 136.56 (7.98) 137.36 (10.61) 0.677 30 minute 129.28 (8.32) 131.0 (8.10) 60 minute 125.2 (6.40) 125.56 (9.42) diastolic blood pressure (mmhg) baseline 81.88 (6.83) 82.16 (6.68) 0.628 30 minute 76.88 (7.23) 78.08 (7.66) 60 minute 73.80 (6.67) 74.28 (7.76) pain severity (7) baseline 9.12 (0.77) 9.04 (0.83) 0.001 30 minute 4.16 (0.88) 5.08 (1.50) 60 minute 2.60 (0.49) 3.08 (0.56) pulse rate (1/minute) baseline 96.12 (4.69) 96.08 (3.42) 0.001 30 minute 79.48 (3.48) 82.88 (4.34) 60 minute 73.72 (2.79) 77.80 (5.97) respiratory rate (1/minute) baseline 17.24 (1.34) 17.04 (1.41) 0.172 30 minute 14.52 (1.11) 15.32 (1.60) 60 minute 13.56 (1.34) 14.04 (1.77) o2 saturation (%) baseline 93.88 (1.79) 93.72 (1.77) 0.933 30 minute 94.28 (1.67) 94.20 (1.64) 60 minute 94.12 (1.59) 94.28 (1.57) temperature (celsius) baseline 37.14 (0.30) 37.01 (0.16) 0.071 30 minute 37.06 (0.20) 36.99 (0.13) 60 minute 37.09 (0.28) 37.09 (0.28) 2.8. outcomes severity of patients’ pain was measured by vas (7) at baseline as well as 30 and 60 minutes after infusion. the patients’ vital signs (blood pressure, pulse rate, respiratory rate, and arterial oxygen saturation) as well as possible side effects such as nausea, vomiting, dizziness, itching and drowsiness were recorded for all patients at minutes 30 and 60. in the case this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jokar et al. 4 figure 1: the flowchart of study. of vas greater than 5 after 30 minute, additional dose of intravenous morphine sulfate was infused in both groups. the amount of the morphine administered to the patients until pain relief was recorded as well. data was recorded by the asthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e25 figure 2: mean pain severity (7) at various times in the two groups. vas: visual analouge scale. sistant emergency medicine specialist, who was not aware of the groupings. moreover, to check for the vital signs and side effects, up to 6 hours after the end of the study, the patients were followed up by checking their blood pressure, heart rate, respiratory rate, and deep tendinous reflexes. clinically significant pain relief was considered as ≥ 3 score decrease of pain severity on vas. 2.9. statistical analysis based on the mean pain scores, in magnesium sulfate and normal saline groups (2.1 ± 1.8 and 1.2 ± 2.9, respectively) (10), alpha error of 5%, and the power of 90%, 50 patients in each group were considered as the sample size. the study analysis approach was that of intention to treat. data were analyzed using stata 13 software through t-test and repeated measure anova. p value less than 0.05 was set as the significance level. 3. results: 3.1. baseline characteristics 100 patients (50 patients per group) were randomly allocated to two treatment groups. patientsâăź flowchart is shown in figure 1. the baseline data for the two groups are shown in table 1. there was no significant difference between the two groups regarding baseline characteristics. although a significant difference was found in body temperature of the patients in the two groups, such a difference is clinically negligible. 3.2. outcomes in table 2, the desired outcome of this study in the baseline, 30 and 60 minutes after intervention are compared between the two groups. repeated measure anova test showed no significant difference for systolic blood pressure (p = 0.677), diastolic blood pressure (p = 0.628), respiratory rate (p = 0.172), oxygen saturation (p = 0.933), and body temperature (p = 0.071) at various times between the two groups. the mean pain severity on vas, however, was significantly different in the groups afer intervention (p = 0.001; figure 2 and table 2). in addition, mean pulse rate in the magnesium sulfate group (p = 0.001) was significantly lower than that of standard protocol group (figure 3). no significant differences in terms of nausea, vomiting, itching and drowsiness were, observed between the two groups. likewise, no cases of dizziness were reported in the groups. the average additional morphine received, in the control group was significantly higher than that of the magnesium sulfate group (1.56 vs 0.96 mg; p = 0.043). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jokar et al. 6 figure 3: mean pulse rate (20) at various times in the two groups. pr: pulse rate. 4. discussion: the findings of present study suggest that adding magnesium sulfate to standard protocol of renal colic management could be effective in reducing the patients’ pain and need for additional dose of morphine sulfate without disturbing hemodynamic measures. however, the amounts of these effects are not clinically significant. magnesium plays key roles in several physiological processes. it has been stated to potentiate lidocaine (7), induce analgesia during spinal anesthesia (11, 12), improve morphine analgesia (13, 14), and reduce consumption of postoperative morphine (15, 16). numerous studies with diverse doses, routes, and methods of administration of magnesium have been conducted with contradictory results (17-19). examining the impact of lowdose magnesium sulfate infusions on pain after laparoscopic cholecystectomy surgery, kocman et al. (20) found that magnesium sulfate significantly reduces post-operative pain. in 2006, safdar et al. (21) study showed that a combination of morphine and ketorolac relief pain better to either drug alone. rezae et al. (2014) examined the effect of magnesium sulfate infusion on pain relief after cesarean section and declared that infusion of 50 mg/kg magnesium sulfate reduces the pain and diminishes the need for other pain medications as well (10). studying the bronchodilating effect of intravenous magnesium sulfate in bronchial asthma, okayama et al. (22) also found that magnesium sulfate infusion can bring about rapid and significant dilation of the bronchi in both mild and severe asthma. their study showed that magnesium sulfate relaxes the smooth muscles of the bronchial wall and dilates the ducts. in our study, adding magnesium sulfate to the standard treatment of patients with renal colic reduced the severity of pain and decreased the need for additional morphine. considering that no side effects have been reported for using magnesium sulfate, as well as its easy application, this drug can be used as an adjunct drug in treatment of patients suffering from renal colic. simultaneous use of magnesium sulfate with other drugs can also reduce their dosage and possible side effects. 5. limitation the main limitation of this study was sample size. due to small sample size and maybe low statistical power, it is recommended that further studies with larger sample sizes be conducted to examine any possible side effects for this drug this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e25 and to confirm or reject the findings of this study. 6. conclusion: the results of this study indicated that magnesium sulfate can be used as an adjunct drug in treatment of patients suffering from renal colic. it can reduce the pain and diminish the need for additional doses of morphine sulfate without disturbing hemodynamic measures. however, the amounts of these effects are not clinically significant. 7. appendix 7.1. acknowledgements hereby we would like to appreciate all those who participated in the study. we would also like to extend our gratitude to arak university of medical sciences for their financial support to this project. 7.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest the authors declare that there is no conflict of interest. 7.4. funding this manuscript was funded by arak university of medical sciences numberd 2185. references 1. kobayashi t, nishizawa k, mitsumori k, ogura k. impact of date of onset on the absence of hematuria in patients with acute renal colic. the journal of urology. 2003;170(4):1093-6. 2. holdgate a, pollock t. systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. bmj. 2004;328(7453):1401. 3. shokeir aa. renal colic: pathophysiology, diagnosis and treatment. european urology. 2001;39(3):241-9. 4. zabihi n, teichman jm. dealing with the pain of renal colic. the lancet. 2001;358(9280):437-8. 5. perlmutter a, miller l, trimble l, marion d, vaughan jr e, felsen d. toradol, an nsaid used for renal colic, decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction. the journal of urology. 1993;149(4):926-30. 6. schlondorff d. renal complications of nonsteroidal anti-inflammatory drugs. kidney international. 1993;44(3):643-53. 7. vastani n, seifert b, spahn dr, maurer k. sensitivities of rat primary sensory afferent nerves to magnesium: implications for differential nerve blocks. european journal of anaesthesiology (eja). 2013;30(1):21-8. 8. sealed envelope ltd. 2016. create a blocked randomisation list. [online] available from: https://www.sealedenvelope.com/simplerandomiser/v1/lists [accessed 24 aug 2016]. 9. ben-ami m, giladi y, shalev e. the combination of magnesium sulphate and nifedipine: a cause of neuromuscular blockade. bjog: an international journal of obstetrics & gynaecology. 1994;101(3):262-3. 10. rezae m, naghibi k, taefnia am. effect of pre-emptive magnesium sulfate infusion on the post-operative pain relief after elective cesarean section. advanced biomedical research. 2014;3. 11. kumar m, dayal n, rautela r, sethi a. effect of intravenous magnesium sulphate on postoperative pain following spinal anesthesia. a randomized double blind controlled study. middle east j anesthesiol. 2013;22(3):251-6. 12. hwang j-y, na h-s, jeon y-t, ro y-j, kim c-s, do s-h. iv infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia. british journal of anaesthesia. 2010;104(1):89-93. 13. bujalska-zadrozny m, duda k. additive effect of combined application of magnesium and mk-801 on analgesic action of morphine. pharmacology. 2014;93(34):113-9. 14. sun j, wu x, xu x, jin l, han n, zhou r. a comparison of epidural magnesium and/or morphine with bupivacaine for postoperative analgesia after cesarean section. international journal of obstetric anesthesia. 2012;21(4):3106. 15. ouerghi s, fnaeich f, frikha n, mestiri t, merghli a, mebazaa m, et al., editors. the effect of adding intrathecal magnesium sulphate to morphine-fentanyl spinal analgesia after thoracic surgery. a prospective, doubleblind, placebo-controlled research study. annales francaises d’anesthesie et de reanimation; 2011: elsevier. 16. albrecht e, kirkham k, liu ss, brull r. peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. anaesthesia. 2013;68(1):79-90. 17. jaoua h, zghidi s, wissem l, laassili s, ammar n, ali j, et al. [effectiveness of intravenous magnesium on postoperative pain after abdominal surgery versus placebo: double blind randomized controlled trial]. la tunisie medicale. 2010;88(5):317-23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jokar et al. 8 18. tramer mr, glynn cj. an evaluation of a single dose of magnesium to supplement analgesia after ambulatory surgery: randomized controlled trial. anesthesia & analgesia. 2007;104(6):1374-9. 19. lysakowski c, dumont l, czarnetzki c, tramer mr. magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials. anesthesia & analgesia. 2007;104(6):1532-9. 20. kocman ib, krobot r, premuzic j, kocman i, stare r, katalinic l, et al. the effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. acta clinica croatica. 2013;52(3):289-94. 21. safdar b, degutis lc, landry k, vedere sr, moscovitz hc, d’onofrio g. intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. annals of emergency medicine. 2006;48(2):173-81. e1. 22. okayama h, aikawa t, okayama m, sasaki h, mue s, takishima t. bronchodilating effect of intravenous magnesium sulfate in bronchial asthma. jama. 1987;257(8):1076-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitation conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e34 or i g i n a l re s e a rc h demographic and clinical characteristics of 907 cases with naltrexone intoxication; a 14-year cross-sectional study mitra rahimi1, alireza kargar2, delara hazegh fetratjoo3, sayed masoud hosseini1, arezou mahdavinejad1, shahin shadnia1∗ 1. toxicological research center, excellence center of clinical toxicology, department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. student research committee, department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 3. department of clinical pharmacy, school of pharmacy, tehran university of medical sciences, tehran, iran. received: february 2022; accepted: march 2022; published online: 1 may 2022 abstract: introduction: opioids have been the leading cause of death from poisoning in iran for several years. this study aimed to evaluate the clinical and para-clinical presentations of naltrexone intoxication, its toxic dose, and its epidemiological properties. methods: this retrospective cross-sectional study was conducted on medical records of patients presenting to toxicology department of loghman hakim hospital, tehran, iran, following naltrexone intoxication, from 2002 to 2016. patients’ demographic and laboratory data, clinical signs, supposed ingested dose, and intent of naltrexone consumption were collected, analyzed, and then interpreted. results: 907 patients with the mean age of 36.6 ±11.7 years were evaluated (94.3% male). the mean amount of naltrexone consumed by the intoxicated patients reported in the medical records was 105.8 ± 267.8 mg. one hundred thirty patients (14.3%) used naltrexone to treat substance use disorder. two hundred eighty-seven poisoned patients (31.6%) were current opium users who intentionally or unintentionally used naltrexone concomitantly. the most common symptoms observed in these patients were agitation (41.8%), vomiting (16.4%), and nausea (14.8%). among patients with naltrexone poisoning, 25 patients were intubated (2.8%), and three passed away. aspartate aminotransferase (ast) levels were significantly higher in patients intoxicated with naltrexone who needed intubation (p = 0.02). conclusion: the probability of intubation of cases with naltrexone intoxication was associated with ast elevation. it seems that, the number of intensive care unit (icu) admissions and mortality rates are not high among these patients. keywords: naltrexone; poisoning; aspartate aminotransferases; cross-sectional studies; retrospective studies cite this article as: rahimi m, kargar a, hazegh fetratjoo d, hosseini sm, mahdavinejad a, shadnia s. demographic and clinical characteristics of 907 cases with naltrexone intoxication; a 14-year cross-sectional study. arch acad emerg med. 2022; 10(1): e34. https://doi.org/10.22037/aaem.v10i1.1554. 1. introduction naltrexone is a long-acting, pure opioid antagonist that blocks mu-receptors and is used in various disorders such as opioid and alcohol use disorder (1). iran is among the countries with the highest prevalence of opioid use disorder, and ∗corresponding author: shahin shadnia; department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. e-mail: shahin1380@gmail.com, https://orcid.org/0000-00029401-0781. opium is the most common substance among these patients (2). afghanistan is the number one producer of opiates globally, which might lead to iran’s highest number of seized opiates in 2018. in addition, opioids have been the leading cause of death from poisoning in iran for several years (3-5). consequently, many opioids and naltrexone poisoning cases are referred to loghman hakim hospital, the most crowded referral poisoning center globally (6). the reduced opioid tolerance caused by naltrexone makes patients vulnerable to opioid overdose after missed doses or discontinuation of treatment (7). three possible causes of death related to naltrexone have been suggested: opioid this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rahimi et al. 2 overdose during naltrexone treatment, opioid overdose after naltrexone treatment discontinuation, and intoxication with naltrexone in patients with opioid use disorder (8). the most common side effects of naltrexone are gastrointestinal (gi) complaints such as diarrhea and abdominal cramping. these adverse effects are analogous to the symptoms of opioid withdrawal, as the mu receptor blockade will increase gi motility. naltrexone has been reported to cause liver damage (when given at doses higher than recommended). it carries an fda boxed warning for this rare side effect. naltrexone may induce a withdrawal syndrome lasting up to 72 hours. it is recommended that the patients spend a period of seven to ten days of opioid abstinence before naltrexone treatment to avoid withdrawal symptoms, such as agitation and restlessness, altered level of consciousness, nausea and vomiting, abdominal pain, diarrhea, myalgia, tachycardia, and dilated pupils (9). this retrospective cross-sectional study aimed to evaluate the clinical and para-clinical presentations of naltrexone intoxication during 14 years in loghman hakim hospital. 2. methods 2.1. study design and setting this research is a retrospective cross-sectional study on medical records of 907 patients with naltrexone intoxication from april 2002 to march 2016 in loghman hakim hospital, in which trained clinical toxicologists record patients’ history and trend of management, as well as their vital signs. this study has been approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.rec.1394.149). all patients’ data were anonymous and identified by the file numbers to preserve patients’ confidentiality. 2.2. participants all the patients who referred to loghman hakim hospital with naltrexone poisoning, both opioid dependent and nondependent, and also all patients with intentional or accidental poisoning were included in this study. all cases of multiple drug toxicity were excluded. since there is no laboratory method in the world to confirm the use of naltrexone, we also relied on the patient’s history of using this drug. 2.3. data gathering demographic data were collected, including age, sex, history and type of drug use disorder, and history of alcohol use disorder. other background data included the amount of naltrexone consumed, clinical characteristics, and lab data. in addition, withdrawal symptoms, electrocardiograms (ecg), arterial blood gases (abg), venous blood gases (vbg), blood electrolytes, and liver and kidney function tests were evaluated. mortality rate, cause of death, and duration of intensive care unit (icu) admission were also analyzed. moreover, the effect of each variable, including demographic and other background data, on need for intubation and duration of hospitalization was assessed. 2.4. statistical analysis the present study used spss 26.0 for windows for data analysis. normality was then examined using the kolmogorovsmirnov and shapiro-wilk tests. in addition, quantitative variables were reported as median and interquartile range (iqr). qualitative variables were also presented as frequency (percentage). additionally, mann-whitney u test and kruskal-wallis test were used to evaluate data with nonnormal distribution, and chi-square test was used to compare categorical variables. the relationship between the duration of hospitalization and other independent quantitative variables was analyzed using spearman correlation analysis. p-values less than 0.05 were considered statistically significant. 3. results 3.1. baseline characteristics of patients medical records of 907 patients with the diagnosis of naltrexone intoxication were studied. the majority of cases were male (855 cases, 94.3%) with a mean age of 36.6 ±11.7 years. the mean amount of naltrexone consumed by the intoxicated patients reported in the medical records was 105.8 ± 267.8 mg. one hundred thirty patients (14.3%) used naltrexone to treat substance use disorder. two hundred eightyseven poisoned patients (31.6%) were current opium users who intentionally or unintentionally used naltrexone concomitantly. the most common symptoms observed in these patients were agitation (41.8%), vomiting (16.4%), and nausea (14.8%). baseline characteristics of patients are presented in table 1. table 2 summarizes the laboratory finding of patients. 3.2. ecg findings among 612 patients whose ecg was examined, 523 patients had normal ecg, 27 patients had right axis deviation, 37 patients had left axis deviation, and one patient experienced st depression. one patient experienced st elevation. two patients had t-flat, and two patients experienced t-invert. 3.3. outcomes among the 907 patients with naltrexone intoxication, evaluated in this study, 759 (83.7%) patients were discharged after completion of the treatment course, 145 (16.0%) patients were discharged against medical advice. three patients were this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e34 table 1: baseline characteristics of patients with naltrexone intoxication variable n values age (year) 878 36.64 ± 11.75 sex male 907 855 (94.3) female 52 (5.7) intoxication characteristics naltrexone dosage (mg) 710 105.83 ± 267.77 time elapsed to presentation 706 4.82 ± 6.31 vital signs temperature (c) 483 36.93 ± 0.3 pulse rate (beats/minute) 839 81.84 ± 11.93 diastolic blood pressure (mmhg) 842 75.64 ± 10.2 systolic blood pressure (mmhg) 852 117.9 ± 15.8 oxygen saturation (%) 26 93.95 ± 7.9 glasgow coma scale 96 13.08 ± 1.92 presenting symptoms vomiting 149 (16.4) nausea 134 (14.8) diarrhea 907 70 (7.7) agitation 379 (41.8) seizure 24 (2.6) outcome intubation 25 (2.8) hospitalization (hour) 27.88 ± 28.8 icu admission 907 56 (6.2) icu stay (hour) 4.82 ± 2.8 mortality 3 (0.3) data are presented as mean ± standard deviation or frequency (%). icu: intensive care unit. n: number of data available regarding that variable on the patients’ profile. deceased (one patient died because of cardiopulmonary arrest, one due to acute tubular necrosis (atn), and the third patient died due to coagulation disorder). there was a significant difference between patients who needed intubation and those who did not in terms of age range (mean rank; 560.58 vs 432.99; p = 0.014), aspartate aminotransferase (ast) level (mean rank; 129.39 vs 96.51; p = 0.02), atrial hco3 (mean rank; 36.5 vs 24; p = 0.049), dose of drug used (less than 100mg vs more than 100 mg; pearson chi-square: 14.5; p = 0.021), and intention of naltrexone use (suicide vs other; pearson chi-square: 4.72; p = 0.03). the duration of hospitalization in patients who consumed more than 100 mg naltrexone was significantly higher than patients who consumed less than 100 mg naltrexone (p = 0.001). 4. discussion in this study, it was shown that naltrexone poisoning was not associated with serious adverse events or high mortality rate, contrary to previous assumptions. naltrexone is a pure competitive opioid antagonist at the mu (µ), kappa (k), and delta (δ) receptors. naltrexone is used orally for patients following opioid detoxification to maintain opioid abstinence and as an adjunct to achieve ethanol abstinence. however, naltrexone should not be administered to an opioid-tolerant patient (10). naltrexone may induce a withdrawal syndrome lasting up to 72 hours (11). hassanian et al. conducted a study from december 2007 to march 2008 in loghman-hakim hospital. among 132 patients who were evaluated, agitation was the most prominent presentation with 96.2% prevalence, followed by altered level of consciousness, nausea, vomiting, abdominal pain, diarrhea, bone and muscle pain, tachycardia, and dilated pupils. except for agitation, no relationship was found between the presence of these symptoms and the dose of naltrexone used (9). furthermore, another cross-sectional study was performed on patients hospitalized with a history of naltrexone use coinciding with opioid substances at razi hospital, rasht, iran, during 20072008. the collected data were demographic information, drug use disorder information, clinical signs and symptoms, laboratory findings, and the therapeutic measures taken. the mean age of the patients was 33.7 ± 10.2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rahimi et al. 4 table 2: laboratory findings of patients with naltrexone intoxication variable n values arterial blood gas analysis ph 56 7.41 ± 0.11 pco2 (mmhg) 51 39.65 ± 34.61 po2 (mmhg) 49 93.69 ± 112.19 hco3 (meq/l) 50 24.14 ± 10.7 base excess (meq/l) 51 0.98 ± 5.47 venous blood gas analysis ph 214 7.3938 ± 0.23 pco2 (mmhg) 214 40.709 ± 27.7 po2 (mmhg) 202 41.000 ± 21.38 hco3 (meq/l) 215 24.714 ± 4.57 base excess (meq/l) 203 2.073 ± 6.55 other laboratory data sodium (meq/l) 763 141.1 ± 4.5 potassium (meq/l) 756 4.2 ± 0.6 blood sugar (mg/dl) 773 108 ± 36.6 hemoglobin (g/dl) 706 13.9 ± 1.7 blood urea nitrogen (mg/dl) 757 30 ± 10.8 creatinine (mg/dl) 758 1 ± 0.4 aspartate transaminase (iu/l) 199 36.2 ± 37.3 alanine transaminase (iu/l) 197 27.1 ± 22 alkaline phosphatase (iu/l) 205 211.7 ± 82.5 creatine phosphokinase (iu/l) 142 767.3 ± 1571.6 lactate dehydrogenase (iu/l) 143 653.7 ± 488.8 data are presented as mean ± standard deviation. pco2: partial pressure of carbon dioxide; ph: potential of hydrogen; po2: partial pressure of oxygen. years. the majority of the cases were male (95.6%) and urban (96.7%). the leading cause of withdrawal symptoms in 91.1% of the patients was inappropriate naltrexone usage. in 80% of the cases, the only poisoning agent consumed was naltrexone. the major clinical features were nausea, vomiting, and agitation. in addition, the primary therapeutic measures were supportive intravenous fluids and methadone administration. the mean hospitalization period was 21.8 ± 18 hours (12). the current study was consistent with the previous studies in terms of general characteristics. the median age of patients was 35, and the male was the dominant sex among patients with naltrexone intoxication. contrary to the primary hypothesis, there was no significant difference between the various age groups regarding clinical consequences. this is probably due to the high prevalence of addiction among this population (13). in accordance with the previous studies, the main clinical presentations among the studied population were agitation, vomiting, nausea, and diarrhea. some cases experienced seizures. these manifestations were mainly due to the withdrawal syndrome caused by naltrexone exposure in opioid-tolerant patients. in another study conducted in australia from 2000 to 2003, the severity and duration of withdrawal symptoms due to accidental or intentional naltrexone abuse were suggested to be variable and unpredictable. oral naltrexone was estimated to have a mortality rate four times greater than methadone in treating patients with opioid use disorder (8). in this study, results revealed that the risk of intubation in patients who were intoxicated with naltrexone with suicidal intention was significantly higher than the patients who were intoxicated due to other reasons (accidental or to quit addiction). analysis revealed that patients who consumed more than 100 mg naltrexone were those who committed suicide. in other words, patients with naltrexone intoxication and suicidal intention were more likely to consume naltrexone more than 100 mg (pearson chi-square=4.5; p<0.03). thus, increased odds of intubation in patients with suicidal intention are probably due to the higher dose of naltrexone exposure in these patients. there are contradictions about naltrexone hepatotoxicity and it does not appear to increase hepatic enzymes at therapeutic doses (14-17). some studies have shown that high doses of naltrexone (up to 400 mg/day) do not affect liver enzyme levels (17). on the contrary, other studies have shown that naltrexone may increase hepatic transaminases at a 300 mg/day dose (18, 19). the present study shows that high levels of ast were assothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e34 ciated with greater need for intubation and more extended hospital stays among patients with naltrexone poisoning. it is recommended to pay more attention to the relationship between elevated ast and the clinical consequences of naltrexone poisoning in future studies. considering that loghman hakim hospital is the scientific center of clinical toxicology and the referral center in iran, so the findings of the study can be generalized, at least, to iran. for future studies, we recommend a prospective study with pre-designed forms to facilitate data entry and prevent missing data in order to aid in preparing a comprehensive and practical protocol for management of naltrexone intoxication. 5. limitations due to the type of research, this study has poor internal validity, which may be negligible due to the importance of the subject and the number of cases studied. moreover, as mentioned above, several cases had missing information regarding the doses of naltrexone, patients’ ages, and their intention for consuming naltrexone. 6. conclusion this study showed that there are many cases of poisoning with naltrexone in iran. the probability of intubation was associated with ast elevation, which may be due to liver damage caused by high doses of naltrexone. it seems that, the number of icu admissions and mortality rates are not high among patients with naltrexone intoxication. 7. declarations 7.1. acknowledgments the authors thank dr maral. ramezani for her kind support. 7.2. authors’ contributions each author’s contribution is in the analytical search for scientific publications, writing the article, and approving the content. 7.3. funding and supports toxicological research center,loghman hakim hospital, shahid beheshti university of medical sciences. 7.4. conflict of interest the authors declare that they have no competing interests. references 1. kirchmayer u, davoli m, verster a. naltrexone maintenance treatment for opioid dependence. cochrane database syst rev. 2003(2). 2. amin-esmaeili m, rahimi-movaghar a, sharifi v, hajebi a, radgoodarzi r, mojtabai r, et al. epidemiology of illicit drug use disorders in iran: prevalence, correlates, comorbidity and service utilization results from the iranian mental health survey. addiction. 2016;111(10):1836-47. 3. shadnia s, esmaily h, sasanian g, pajoumand a, hassanian-moghaddam h, abdollahi m. pattern of acute poisoning in tehran-iran in 2003. hum exp toxicol. 2007;26(9):753-6. 4. ghane t, zamani n, hassanian-moghaddam h, beyrami a, noroozi a. lead poisoning outbreak among opium users in the islamic republic of iran, 2016–2017. bull world health organ. 2018;96(3):165. 5. merz f. united nations office on drugs and crime: world drug report 2017. 2017. sirius. 2018;2(1):85-6. 6. hassanian-moghaddam h. an educational and research opportunity for the largest university hospital poison control centers; tehran and cairo. egypt j forensic sci. 2013;2(3):64-5. 7. strang j, mccambridge j, best d, beswick t, bearn j, rees s, et al. loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. bmj. 2003;326(7396):959-60. 8. gibson ae, degenhardt lj. mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records. drug alcohol rev. 2007;26(4):405-10. 9. hassanian-moghaddam h, afzali s, pooya a. withdrawal syndrome caused by naltrexone in opioid abusers. hum exp toxicol. 2014;33(6):561-7. 10. nelson l, howland m, lewin n, smith s, goldfrank l, hoffman r. chapter 4: principles of managing the acutely poisoned or overdosed patient. goldfrank’s toxicologic emergencies, 11th ed new york, ny: mcgrawhill education online edition accessed september. 2019;25:2021. 11. pope jf. clinical management of poisoning and drug overdose. clin pediatr. 1998;37(7):457. 12. rahbar m, badsar ar, mahmanzar ch, fallah m. the study of the demographic and clinical and laboratory findings in naltrexone poisoning patients admitted to razi hospital, rasht, during 2007-08. iran j toxicol. 2012;17(6):649-654. 13. mokri a. brief overview of the status of drug abuse in iran. arch iran med. 2002;5(3):184-190. 14. yen m-h, ko h-c, tang f-i, lu r-b, hong j-s. study of hepatotoxicity of naltrexone in the treatment of alcoholism. alcohol. 2006;38(2):117-20. 15. vagenas p, di paola a, herme m, lincoln t, skiest dj, altice fl, et al. an evaluation of hepatic enzyme elevations among hiv-infected released prisoners enrolled this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rahimi et al. 6 in two randomized placebo-controlled trials of extended release naltrexone. j subst abuse treat. 2014;47(1):35-40. 16. brewer c, wong vs. naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literature. addict biol. 2004;9(1):81-7. 17. marrazzi ma, wroblewski jm, kinzie j, luby ed. highdose naltrexone and liver function safety. am j addict. 1997;6(1):21-9. 18. mitchell je, morley je, levine as, hatsukami d, gannon m, pfohl d. high-dose naltrexone therapy and dietary counseling for obesity. biol psychiatry. 1987;22(1):35-42. 19. pfohl dn, allen ji, atkinson rl, knopman ds, malcolm rj, mitchell je, et al. naltrexone hydrochloride (trexan): a review of serum transaminase elevations at high dosage. nida res monogr. 1986;67:66-72. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e23 or i g i n a l re s e a rc h relationship between income level and hospitalization rate in covid-19 cases; an example of social factors affecting health ali maher1, hamed dehnavi1∗, elham salehian2, mona omidi2, khatereh hannani2 1. department of health management and economics, virtual school of medical education and management, shahid beheshti university of medical sciences, tehran, iran. 2. resources development deputy, shahid beheshti university of medical sciences, tehran, iran. received: february 2022; accepted: march 2022; published online: 9 april 2022 abstract: introduction: considering the population’s socioeconomic status and clinical features is essential in planning and performing interventions related to disease control. the main purpose of this study was to investigate the relationship between income level and hospitalization rate of covid-19 patients. methods: a cross-sectional study was performed on 198,944 hospitalized covid-19 patients in tehran province between march 2020 and march 2021. data of hospitalized covid-19 patients was obtained from the hospital intelligent management system (him). the income data of patients were obtained from the iranian database on targeted subsidies belonging to the ministry of cooperatives, labor, and social welfare. data analyses were performed using spss software. results: about 2.5% of the inpatients were from the first decile, while 20.6% were from the tenth. the share of the lower three deciles of total hospitalization was about 11%, while the share of the upper three deciles was 50%. there was a big difference between the upperand lower-income deciles regarding death rates. in the first decile, 30% of inpatients died, while the proportion was 10% in the tenth decile. there was a significant and positive relationship between income decline and hospitalization (r = 0.75; p = 0.02). also, there was a significant and negative relationship between income decline and death rate (r = -0.90; p = 0.01). conclusion: low-income groups use fewer inpatient services, are more prone to severe illness and death from covid-19, and treatment in this group has a lower chance of success. using a systemic approach to address socioeconomic factors in healthcare planning is crucial. keywords: covid-19; iran; income; socioeconomic factors; health services accessibility cite this article as: maher a, dehnavi h, salehian e, omidi m, hannani k. relationship between income level and hospitalization rate in covid-19 cases; an example of social factors affecting health. arch acad emerg med. 2022; 10(1): e23. https://doi.org/10.22037/aaem.v10i1.1600. 1. introduction on december 8, 2019, china reported a type of coronavirus that caused an infectious disease with symptoms such as fever, cough, and shortness of breath. on january 6, 2020, the world health organization named the disease covid-19 (1). more than 220 million confirmed cases have been reported since the epidemic began, and more than 4.5 million people have died. the highest rates of death have been reported in ∗corresponding author: hamed dehnavi; department of health management and economics, virtual school of medical education and management, valiasr avenue, tehran, iran. tel: +982126214956, email: hamedehnavi@gmail.com, orcid: http://orcid.org/0000-0002-8183-4458. the united states, europe, and southeast asia (2). the effects of this crisis in various dimensions are not yet fully known. the world health organization has called covid-19 a humanitarian crisis and described it as more than a health crisis. estimates have shown that covid-19 is likely to increase global poverty and inequality, so achieving sustainable development goals (sdgs) will certainly require more effort (3). covid-19 has cost the world more than $10 trillion so far, and more than 10 million people worldwide are affected by poverty for every percentage drop in the global economy (4). nearly 80% of the world’s population lives in lowand middle-income countries (lmics) and, therefore, faces extra pressure because there is not sufficient infrastructure and facilities (5). consequently, it is crucial to find effective strategies in each country. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. maher et al. 2 health is related to the socioeconomic status (ses) of demographic groups in complex ways. in other words, inequality in social determinants of health (sdh) leads to inequality in health. inequality in health exists not only between the rich and the poor, but at every level of socioeconomic status (6, 7). a review of data from 178 countries/regions indicates that socioeconomic factors can significantly affect the risk of covid-19 (8). poor people who do not usually have access to health services are more vulnerable in times of crisis (4). low socioeconomic status (ses) is widely associated with disease and mortality. people with lower ses are more likely to be affected by covid-19 (9-13). studies in various countries, including the united states (5), brazil (14), africa (15), the united kingdom (16), sweden (10), scotland (17), and france (18), confirm this claim. based on these studies, sex (9, 10), education (10), income (5, 10, 19), place of residence (city or village) (9), race and ethnicity (11, 12, 20), underlying diseases (21) and living in areas with high population density (22) affect the incidence and mortality of covid-19. in general, when the level of ses improves, the severity and complications of the disease decrease (23). thus, the interaction of covid-19 and socioeconomic status creates a combination that imposes the burden of inequality on disadvantaged people in society (10). the first cases of coronavirus in iran were reported in late february 2020. by july 2021, five waves of disease outbreaks have occurred. to date, about 5 million cases have been confirmed, and approximately 110,000 patients have died from the disease. iran has faced many challenges in early dealing with the disease. political and economic sanctions have greatly affected the country’s economy. in iran, infrastructure development, capacity building, and resource allocation to control the epidemic and treatment of patients face many challenges (24). concerns about protecting vulnerable groups have increased in the wake of the covid-19 crisis, followed by the global economic downturn and countries’ focus on ensuring population health (22). considering the relationship between socioeconomic factors of patients and covid-19 mortality is crucial to targeting vulnerable groups (25). a study conducted in tehran demonstrated that those with lower economic status were more at risk of morbidity and mortality (26). despite the studies conducted in iran on the effect of socioeconomic factors, there is no study that clearly shows the impact of income yet. we aimed to investigate relationship between covid-19 mortality and income level of patients. the findings of this study can highlight the gap in access to and utilization of health care services due to socioeconomic differences in tehran province. 2. methods 2.1. study design and setting this cross-sectional study was performed on hospitalized covid-19 patients in tehran province. tehran province has an area of about 13,000 square kilometers, and according to the official census, in 2016, its population was 13,267,000. about 16.6% of the country’s population lives in tehran province. health services in tehran province are provided by three medical universities: shahid beheshti, tehran, and iran. about 17% of hospitals and 22% of hospital beds in the country are located in tehran province (27). the protocol of the study was approved by ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.sme.rec.1400.086) and the researchers adhered to the confidentiality of patients’ profiles. 2.2. data collection and procedure the study sample consists of all inpatients with positive pcr hospitalized from march 20, 2020, to march 20, 2021 in tehran province. we obtained inpatient information from the hospital intelligent management system (him) of shahid beheshti university of medical sciences. the intelligent hospital management system is a management information system (mis) that aggregates data from various systems and provides them in dashboards and reports for managers. the data of covid-19 patients were collected directly from the hospital information system (his). all the data recorded in the hospital were directly entered into the study and there was no missing data in the data collection stage. the income data of patients were obtained from the iranian ministry of cooperatives, labor, and social welfare. patients’ income and hospitalization information were matched using a national code. the statistics center of iran categorizes families into ten groups based on total annual income in the annual household budget report. the first decile is the lowest income group, and the tenth decile is the highest income group of families. the use of him data was done after receiving ethical approval from shahid beheshti university of medical sciences regarding the use of data. 2.3. definition in its annual household budget report, the statistics center categorizes households into ten groups based on total annual income and expenses. the first decile is the lowest income group, and the tenth decile is the highest income group of families. the statistics center examines each decile’s types of costs and characteristics and announces them in different tables. in 2021, if the total cost of a household is about $64 per month, this family will be in the first decile and is among the poorest 10% of society. the cost of a household is about this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e23 table 1: frequency of hospitalization and mortality of covid-19 patients based on the income decile income decile hospitalized recovered deceased 1 4920 (2.5) 3460 (2.0) 1460 (6.1) 2 7451 (3.7) 5997 (3.4) 1454 (6.1) 3 9723 (4.9) 8349 (4.8) 1374 (5.8) 4 14379 (7.2) 12339 (7.0) 2040 (8.6) 5 18721 (9.4) 16019 (9.1) 2702 (11.3) 6 20746 (10.4) 18196 (10.4) 2550 (10.7) 7 23606 (11.9) 21063 (12.0) 2543 (10.7) 8 26928 (13.5) 24289 (13.9) 2639 (11.1) 9 31516 (15.8) 28458 (16.3) 3058 (12.8) 10 40954 (20.6) 36929 (21.1) 4025 (16.9) total 198944 (100) 175099 (100) 23845 (100) data are presented as number (%). figure 1: income deciles and rate of hospitalization and mortality among covid-19 cases. $640 in the tenth decile, which consists of the richest 10% of people in society (28). 2.4. data analysis the data were assessed in several steps. the frequencies of patients were calculated in terms of income deciles. spss software version 24 was used to perform calculations and data analysis. descriptive statistics and frequency distribution were used as appropriate. spearman’s correlation coefficient was used to test the significance of the hospitalization and death rate differences between income deciles. results were presented in graphs and tables. 3. results over the study period, 198,944 patients were hospitalized; 88% (n=175,099) recovered and were discharged from the hospital, and 12% (n=23845) died (table 1). with increase in income, the number of patients also increased. the number of hospitalizations in the first income decile was 4,920 (2.5% of total hospitalization), and in the tenth decile was 40,954 (20.6% of total hospitalization). the number of hospitalizations in the tenth decile was 8.3 times that of the first decile. in the same way, the number of death and recovered patients also increased with rise in the income decile. the share of the lower three deciles was 11.1% of the total hospitalizations, while the share of the upper three deciles was 50%. the death rates decreased from the deprived decile to the rich decile. there was a big difference between the deprived and wealthy deciles in terms of death rates. in the first decile, 30% of hospitalized patients died, while the rate was 10% in the tenth decile. the death rate in the studied province was 12%. death rates in the upper seven deciles were between 10 and 14%. as figure 1 shows, there were two opposing trends between the death in income deciles and their share of total hospitalization. the first decile has the lowest hospitalization rate (2.5%), while the highest death rate belonged to this decile (30%). the tenth decile has the highest hospitalization rate (20.6%), while it has the lowest death rate (9.8%). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. maher et al. 4 there was a significant and positive relationship between income decline and share of total hospitalization (r = 0.75; p = 0.02). also, there was a significant and negative relationship between income decline and death rate (r = -0.90; p = 0.01). 4. discussion this study aimed to investigate the relationship between income deciles and the number of hospitalizations and deaths among covid-19 cases. the results showed that inpatient service utilization had increased with the increase in income. on the other hand, more low-income people died because they could not afford it. health is considered one of the fundamental human rights. a comprehensive approach to health care is closely related to social and economic conditions, physical environment, and lifestyle. the commission on social factors affecting health considers health inequalities to be the result of decades of gradual exposure to health risks among those who have lived in deprivation (19). several studies have reported a higher prevalence of non-communicable diseases (ncds) in disadvantaged groups compared to populations with higher socioeconomic status (15, 29). inequalities were rising in many parts of the world before the covid-19 epidemic. the current crisis seems to be increasing these inequalities (30). vulnerability is one of the main components of getting exposed to the risk and influence of covid-19. groups in the community are not equally affected by diseases. vulnerable groups, including the elderly and those with underlying diseases, have higher mortality rates. covid-19 highlights the societal gaps and is likely to deepen existing inequalities (16). socioeconomic status (ses) can expose people to disease and death in various ways. people’s jobs can expose them to more viruses and infections. in addition, smoking and a poor diet that reduces the body’s immune system will increase the risk of infection (13). a study by su et al. using data from 178 countries/regions showed that socioeconomic factors could be significantly associated with the risk of covid-19. a study in tehran, which examined the spatio-temporal patterns of the epidemic, showed that demographic composition and major physical characteristics at the neighborhood level were important factors explaining the high rate of infection and mortality. population density and facility distribution patterns were the most critical factors in this regard. hot spots were observed in areas with low socioeconomic status (26). another study in tehran showed that health awareness level was higher in areas with high socioeconomic status (northern part of the city), and the higher death rate in the eastern parts of tehran could be associated with lower socioeconomic status; since people with low socioeconomic status seek health services only in the advanced stages of the disease (31). a study conducted by clouston et al. in the united states showed that cities with a high percentage of high-risk residents, including minors and the elderly had higher mortality rates. residents of cities with higher ses were at lower risk of covid-19 mortality than those living in cities with low ses (32). additionally, in chicago about 70 percent of deaths occurred in black people, while they made up only 30 percent of the population. (30). this study showed that the death rate of patients in low-income deciles in the province is higher. a large number of studies reported similar results. a survey of the health transformation plan (htp) impact in iran on catastrophic costs showed that the provinces had different catastrophic health expenditure (che) rates, which may be affected by various socioeconomic factors. literacy and employment rates should be increased to protect patients from catastrophic health expenditure (32, 33). a study by sesé et al. in seine-saint-denis (ssd), france, the poorest area of paris, showed that the cause of higher death rates in this area was lower ses (18). a study by navaratnam et al. on covid-19 inpatients in uk hospitals showed that more deprivation was associated with a higher risk of death (34). various authors, including wilkinson, show that people’s health is a function of their income (absolute income hypothesis). regarding income inequality, the relative income hypothesis shows that income inequality has a negative impact on population health. inequality is recognized as a critical risk factor for community health (19, 35). the evidence clearly shows that there is a non-linear relationship between health and income. accordingly, redistributing income from the rich to the disadvantaged can help improve health indicators (19). low income affects life in many ways. living in more deprived neighborhoods and housing conditions (especially small or overcrowded housing) increases the risk of infection (13). a study in new york wards found that the rate of hospitalization and mortality was lowest among residents of manhattan’s most affluent area, where the population is predominantly white (20). in sweden, a study by rafal et al. showed that being a man, having a lower personal income, lower education, and being single increased the risk of death from covid-19 (10). a study by rose et al. in the united kingdom on the relationship between income levels and deaths from covid-19 showed that each percent increase in the proportion of the population experiencing income deprivation was associated with a 2% increase in deaths from covid-19 (30). a study by lone et al. in scotland on covid-19 patients admitted to the intensive care unit (icu) showed that patients living in disadvantaged socioeconomic areas were more likely to need icu admission and had higher mortality rate after 30 days. icu wards in more deprived areas had higher bed occupancy rate (bor), and the average length of stay (alos) was higher (17). people who have limited acthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e23 cess to health care and have covid-19 symptoms may delay their treatment or even hide their sickness. as a result, they may seek health services only in the late stage of the disease. this condition reduces the chance of recovery and increases the likelihood of transmission to others (22). although it has been argued that all countries should pursue a quarantine policy to prevent the rapid spread of the disease due to the irreversible consequences of the pandemic, low-income people are forced to go out of home due to economic pressures (36). those who live in areas with higher socioeconomic deprivation are more likely to live in crowded neighborhoods that are more prone to disease. more people have non-communicable diseases (ncd), such as high blood pressure, obesity, diabetes, and heart disease in socioeconomically disadvantaged areas. these factors increase the severity of the disease and raise the need for icu admission and the risk of death (17). this study demonstrated that low-income groups use fewer inpatient services, but more hospitalized covid-19 patients die from the disease. one reason is the treatment-seeking behavior of this group. minorities and disadvantaged people pay less attention to the disease and delay treatment (37). disease control and early detection are essential in controlling covid-19 before the disease progresses; otherwise, patients are less likely to survive. 5. limitation this study has a limitation. data related to patients’ income deciles were not provided directly to the research team due to confidentiality. it was impossible to analyze the patients’ income data one by one. data matching was performed using the national code. for this purpose, the national code of patients was sent to the iran ministry of cooperatives, labor, and social welfare. the experts of that organization matched the data with confidentiality. 6. conclusion the findings of this study demonstrated that low-income groups use fewer inpatient services, and treatment in this group has a lower chance of success. planning to identify vulnerable people in the early stages of the disease and increase their access to health services will help improve community health and reduce health sector costs in tehran. 7. recommendations for future research further studies on why low-income groups do not use inpatient services and the reasons for delays in receiving services can complement the findings of this study and help interpret the findings. 8. clinical implications for health managers and policymakers paying attention to low-income deciles in tehran province and identifying their health needs should be one of the priorities of policymakers and managers of the health system. targeting available resources and building more capacity based on socioeconomic studies is vital in managing and ending the covid-19 epidemic. 9. abbreviations sdgs: sustainable development goals ses: socioeconomic status sdh: social determinants of health ncds: non-communicable diseases htp: health transformation plan bor: bed occupancy rate alos: average length of stay 10. declarations 10.1. acknowledgments the authors thank the reviewers who helped improve the article with their comments. the ethics committee approval code is ir.sbmu.sme.rec.1400.086. 10.2. authors’ contributions am designed the study. am, kh and es collected the data. am, hd analyzed and interpreted the data. ah, hd and mo drafted the manuscript. all authors have read and approved the final manuscript. 10.3. availability of data and materials the data that support the findings of this study are available from the iranian ministry of health. however, restrictions apply to the availability of these data, which were used under license for the current research, and so are not publicly available. however, data are available from the authors upon reasonable request and with permission of iranian ministry of health. 10.4. funding no funds were used for the study. 10.5. competing interests the authors declare that they have no competing interests references 1. mosadeghrad am, dehnavi h, isfahani p. predicting covid-19 epidemics using google search trends. health this 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study using administrative data. lancet respir med. 2021;9(4):397-406. 35. wilkinson rg. income distribution and life expectancy. british medical journal. 1992;304(6820):165-8. 36. omidi m, maher a, etesaminia s. lessons to be learned from the prevalence of covid-19 in iran. med j islam repub iran. 2020;34(1):398-9. 37. united nations. a un framework for the immediate socio-economic response to covid-19. united nations new york; 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion recommendations for future research clinical implications for health managers and policymakers abbreviations declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 180 emergency 2014; 2 (4): 180-182 case report pneumatic rupture of rectosigmoid; a case report mohammad montazeri1, bahman farhangi2, mahmood montazeri1* 1. young researchers club, islamic azad university, babol branch, babol, iran 2. department of general surgery, shahid beheshti hospital, mazandaran university of medical sciences, babol, iran abstract pneumatic rectosigmoid rapture is usually occurred following the inappropriate fun by direct entering a high volume of the air through the pneumatic device to the anus. such an event was reported for the first time in 1904 by stone. diagnosis and treatment of such injuries are often delayed because of some social limitations and preventing the patient form explaining the event. colon sigmoid rupture and pneumoperitoneum is one of the most dangerous and life treating complications of entering a high volume of the air to the rectum in a short time. there are only a few reports regarding the similar cases. here, a case of pneumatic rectosigmoid rapture was reported in a 53 yearold male following an inappropriate fun. key words: pneumoperitoneum, artificial; rupture; abdomen, acute cite this article as: montazeri m, farhangi b, montazeri m. pneumatic rupture of rectosigmoid; a case report. emergency. 2014;2 (4):180-2. introduction:1 neumatic rectosigmoid rupture is usually occurred following the inappropriate fun by direct entering a high volume of the air through the pneumatic device to the anus (1). there are only a few reports regarding the similar cases. such an event was reported for the first time in 1904 by stone (2). then andrews in 1911 declared a patient with sigmoid rapture who was treated by resection of torn region (3). diagnosis and treatment of such injuries are often delayed because of some social limitations and preventing the patient form explaining the event. colon sigmoid rupture and pneumoperitoneum is one of the most dangerous and life treating complications of entering a high volume of the air to the rectum in a short time (4). here, a case of pneumatic rectosigmoid rapture was reported in a 53 year-old male following an inappropriate fun. case presentation: a 53 year-old patient with complaining of faint and abdominal pain referred to the emergency department. his problem was suddenly initiated with rectoragy and lower abdominal pain in the admission morning. at first he referred to the outpatient clinic, underwent supportive treatment, and then discharged without a clear diagnosis. after a short time, he experienced non-bloody vomiting of eaten stomach content as well as rectoragy, again. also the abdominal pain exacerbated and expanded to across the abdomen. shortness of breathing was gradually add *corresponding author: mahmood montazeri; young researchers club, islamic azad university, babol branch, babol city, mazandaran province, iran. tel: +98 111 2415102; email: mm.montazeri@gmail.com; received: august 2014; accepted: august 2014 ed to other problems of the patient, too. by increasing the patient’s symptoms, he was referred to the emergency department by his colleagues. the patient did not explain anything regarding his trauma event and stated that he had has these symptoms since the morning. in the arrival time the patient was alert but complained from severe abdominal pain and rectoragy. during visiting the abdomen was distant with general guarding and tenderness. the abdomen was tympan in palpitation and dullness of the liver wiped out. visiting of the rectum showed no signs of trauma or injury. after comprehensive history taking and physical examination, laboratory tests as well as a simple standing chest radiography was requested. the patient’s vital signs at the time of admission were as follow: blood pressure= 120/80 mmhg, pulse rate= 100/minutes, respiratory rate= 20/minutes, temperature= 37.5 °c oral, and saturation oxygen= 91% on room air. plain chest radiograph revealed a high volume of free air under the both sides of diaphragm (figure 1). then, the patient experienced fever during hospitalization (39 °c oral). considering to the signs, the subject underwent laparotomy after the initial resuscitation. immediately after opening the peritoneum, the air quickly exited and abdominal distension relieved rapidly. the exploration showed a gangrene and about six centimeters perforation at anti-mesenteric border of the rectosigmoid. in careful observation of the peritoneal space no other injuries were found. after clearing the peritoneal cavity, the patient underwent hartmann’s colostomy and also hemovac drain was placed. after full consciousness of the patient and his informing from the occurred event, he stated that in the refer morning before beginning of the symptoms, his colleagues for the fun entered p mailto:mm.montazeri@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 181 montazeri et al the compressed air through the tube air compressor (with pressure lbs 50) into his anal. two weeks after surgery, the patient was discharged in a good condition. discussion: pneumatic rectosigmoid rupture usually happen following the joke and in work places using compressed air. among pneumatic traumas, colon injury is very serious due to entering a high volume of the air to the rectum in a short time. the symptoms are different depend on the intraluminal pressure and level of colon injury. colon rapture can be occurred in one or more sites but as shown in the subject of the present study, the most current region of the rapture is the rectosigmoid location especially in the recto-sigmoid junction (5). the high pressure air which is entered to the rectum exercises a large force to the rectosigmoid junction which leads to rapturing the anti-mesenteric wall of the rectosigmoid (3). the abdominal distension and pain are suddenly initiated and peritoneal symptoms like abdominal rigidity and tenderness presented as the subject of our study. due to hampering the movement of diaphragm by pneumoperitoneum, in most of times respiratory distress occurs, too (4). zechel divided the shock of pneumatic injuries in to two groups (6). the initial shock is because of entering the compressed air and colon rapture while the second shock arises from the pressure pneumoperitoneum. in the pressure pneumoperitoneum too much pressure in the peritoneum forces to the cardiovascular and respiratory system and leads to hypotension and respiratory distress. after resuscitation of the initial shock, peritonitis due to fecal contamination should be evaluated and quickly treated (1). the inflamed colon filled with air or large amount of free air in peritoneal space was seen in radiography. when the respiratory distress associates with such radiological presentation, arterial blood gas (abg) shows hypoxia and respiratory alkalosis. increasing the air pressure inside of the peritoneal space can affect superior vena cava (svc) and collapse the blood flow, severe impairment of blood flow leads to rhabdomyolysis (7). although patients with pneumatic rapture of colon were diagnosed in the initial visit, some cases with delayed diagnosis were also reported (8-10). such patients firstly did not show any peritoneal symptoms or air trapped in the peritoneal cavity in the simple chest radiography, but after three to five days the peritoneal symptoms would gradually appear. shiels and colleagues showed that a pressure of 120 mmhg is required to colon perforation by hydrostatic enema (11); also in the present subject such a pressure was occurred by injecting the air to the anus. of course deter mining the reason of perforation, arisen from the direct trauma or hydrostatic pressure, is difficult. treatment of pneumatic injury has two aspects: pressure pneumoperitoneum and colon injury. pressure pneumoperitoneum mostly causes to acute respiratory distress with or without cardiovascular collapse and in the absence of emergency peritoneal paracentesis it will lead to death. colon perforation should be separately treated. for the perforated colonic ulcer, the primary repair or segmental resection with or without colostomy would be performed, too (4). it could be concluded that despite uncommonness of pneumatic rectosigmoid rupture, it should be considered as one of the differential diagnosis in the presence of free air in abdominal cavity and sign of peritoneum. acknowledgments: none conflict of interest: authors declared no conflict of interest. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. kumar r, rowe t, dave p. pneumatic rupture of colon. postgrad med j. 1971;47(551):631-2. 2. stone g. rupture of bowel caused by compressed air. the lancet. 1904;164(4221):216-7. 3. andrews ew. pneumatic rupture of the intestine, a new type of industrial accident. surg gynecol obstet. 1911;12:6372. 4. kim sj, ahn si, hong kc, kim js, shin sh, woo zh. pneumatic colonic rupture accompanied by tension pneumoperitoneum. yonsei med j. 2000;41(4):533-5. figure 1: the upright posterior-anterior chest x ray of patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 182 emergency 2014; 2 (4): 180-182 5. brown rk, dwinelle j. rupture of the colon by compressed air: report of three cases. ann surg. 1942;115(1):13. 6. zechel gl. pneumatic rupture of the colon as an industrial injury. ind med surg. 1967;36(10):663-7. 7. kinjyo t, ohno t, tanaka k, nishimura a, taira a. compressed air injury of the colon complicated by rhabdomyolysis: case report. j trauma. 1994;36(4):592-3. 8. raina s, machiedo gw. multiple perforations of colon after compressed air injury. arch surg. 1980;115(5):660-1. 9. gemer m, feuchtwanger mm. pneumatic rupture of the colon: sequential appearance of symptoms. jama. 1975;233(4):355. 10. comline j. pneumatic rupture of the colon. br med j. 1952;1(4761):745. 11. shiels 2nd w, kirks d, keller g, et al. john caffey award. colonic perforation by air and liquid enemas: comparison study in young pigs. am j roentgenol. 1993;160(5):931-5. emergency. 2017; 5 (1): e16 or i g i n a l re s e a rc h protocol adherence for severe sepsis and septic shock management in emergency department; a clinical audit mostafa alavi-moghaddam1, ali anvari2∗, reaza soltani delgosha1, hamid kariman1 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye pakdasht hospital, shahid beheshti university of medical sciences, tehran, iran. received: june 2016; accepted: july 2016; published online: 9 january 2017 abstract: introduction: although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. this study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ed) according to the present standard guidelines. methods: this is a prospective audit on approaching adult septic patients who were admitted to ed. the audit checklist was created based on the protocols of surviving sepsis campaign and british royal college recommendations. the mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using spss version 21. results: 30 emergency medicine residents were audited (63.3% male). the mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (iqr = 2) in pre education and 8.17 ± 1.31 (iqr = 85) in post education phase (p < 0.001). there was excellent compliance with standard in 4 (22%) studied measures, good in 2 (11%), fair in 1 (6%), weak in 2 (11%), and poor in 9 (50%). 64% of poor compliance measures correlated to therapeutic factors. after training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow o2 therapy were improved clinically, but not statistically. conclusion: the protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow o2 delivery were disappointingly low. it seems training workshops and implementation of clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock. keywords: sepsis; shock, septic; disease management; guideline adherence; clinical audit © copyright (2017) shahid beheshti university of medical sciences cite this article as: alavi-moghaddam m, anvari a, soltani delgosha r, kariman h. protocol adherence for severe sepsis and septic shock management in emergency department; a clinical audit. emergency. 2017; 5 (1): e16. 1. introduction sepsis is a critical condition, which is characterized by immune system response to bacterial infections that can lead to acute organ failure (1-4). despite significant developments in the field of medicine, sepsis is still a major issue threatening humans’ lives (5). the increasing incidence rate of severe sepsis and septic shock during the past three decades has led to sepsis becoming the second main cause of death among shock patients. the mortality rate among septic patients strongly correlates with organ dysfunction (6). based on previous studies, the mortality rate of severe ∗corresponding author: ali anvari; emergency department, shohadaye pakdasht hospital, pakdasht, varamin, tehran, iran. tel: 00989123162421 email: anvariali00@gmail.com sepsis and sepsis shock were 25-30% and 40-70%, respectively (7, 8). controlling the inflammation processes can prevent sepsis from turning into septic shock and damage to vital organs, therefore, decrease the mortality and morbidity of these patients (9). according to this theory, surviving sepsis campaign recommended a guideline with the aim of diagnosis and treatment of septic patients to improve the prognosis (10). institute for healthcare improvement also recommend protocols for resuscitation of severe sepsis and septic shock patients in the first four hours of diagnosis. however, still many defects exist in approaching and managing these patients (11-14)(19-22). this study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ed) according to the present standard guidelines before and after the training workshop this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. alavi-moghaddam et al. 2 2. methods 2.1. study design this is a prospective audit on approaching adult septic patients who were admitted to the ed of imam hossein educational hospital, tehran, iran, during october 2010 to may 2011. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences. researchers adhered to all helsinki recommendations and confidentiality of patient profiles during the study period. 2.2. data collection data gathering was performed using a predesigned standard checklist and convenience sampling method. the audit checklist was created based on the protocols of surviving sepsis campaign and british royal collage recommendations (14-16). checklist items were categorized into two groups of diagnostic and treatment measures. these measures consisted of checking vital signs within 20 minutes of admission (blood pressure, pulse rate, respiratory rate, temperature, oxygen saturation), blood sugar, arterial blood gas (abg) parameters, urine output; blood culture request; inserting central venous line and checking central venous pressure in the first 2 hours of admission; ordering and administration of high flow oxygen; fluid resuscitation with crystalloid; antibiotic therapy; administration of vasopressor and positive inotrope agents; blood transfusion; and orotracheal intubation. minimum ideal compliance rate for each measures according to the local condition were defined as follows: checking vital sign and abg for 95% of patients; administration of high flow oxygen for 95%; administration of intravenous fluid for 75% in the first hour of admission, 90% in the second hour, and 100 before leaving ed; initiation of intravenous antibiotic for 50% in the first hour, 90% in the second hour, and 100% before leaving ed; and checking urine output for 90% before leaving ed. 2.3. audit phases in the first phase of study (about 3 months), management of septic patients by emergency medicine residents was evaluated using the mentioned checklist and the time from ed presentation to reaching a diagnosis was recorded. a trained emergency medicine resident was responsible for real time checking and recording of required items for each patients. then, the faults and shortcomings of management were extracted and a training workshop was held for all in charge emergency medicine residents. in the second phase (1 month after finishing education) performance of the same residents in management of septic shock and severe sepsis was reevaluated using the same checklist (about 3 months). 2.4. statistical analysis data were analyzed using spss version 21. variables were presented as frequency and percentage, inter quartile range (iqr), and mean ± standard deviation. the compliance rates were categorized into five groups based on likert scale: ≥ 90% as excellent (score 5), 80-90% good (score 4), 70-80% fair (score 3), 60-70% weak (score 2) and < 60% poor (score 1). comparisons were made using student t test, wilcoxon, and chi square tests. p < 0.05 was considered as statistically significant. 3. results: 30 emergency medicine residents were audited regarding management of severe sepsis and septic shock. the mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (iqr = 2) in pre education and 8.17 ± 1.31 (iqr = 2) in post education phase (p < 0.001). the median time from admission to diagnosis were 55 and 15 minutes in pre and post training phases, respectively (p < 0.001). there were excellent compliance with standard in 4 (22%) studied measures, good in 2 (11%), fair in 1 (6%), weak in 2 (11%), and poor in 9 (50%). 64% of poor compliance measures correlated to therapeutic factors. table 1 compares compliance rate of different studied measures with standard guidelines between pre and post training periods. after training, score of 5 measures including checking vital signs in < 20 minutes, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow o2 therapy were improved clinically, but not statistically. 4. discussion: based on the findings of the present study, there was fair (70-80%) to poor (<60%) compliance with standard protocol regarding 64% of studied measures in management of severe sepsis and septic shock. it reduced to 55% after training workshops. the protocol adherence for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow o2 delivery were disappointingly low in both pre and post training periods. the mean time from arrival to ed and reaching diagnosis was significantly decreased after training. the study of miller et al. showed that by performing the protocols accurately, the rate of death decreased (12). catenacci et al. reported that evaluating the severe sepsis patients according to protocols caused 16 percent decrements in the rate of mortality (17). administrating high flow oxygen was significantly increased from 10% to 40% of patients after training, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e16 table 1: comparison of compliance rate of different studied measures with standard guidelines between pre and post education periods studied measures pre education post education p value % (n) rate* % (n) rate vital signs (<20 minute) 86.7 (26) good 90 (27) excellent 0.999 o2 saturation ( <20 minute) 86.7 (26) good 90 (27) excellent 1.000 blood sugar 93.3 (28) excellent 96.7 (29) excellent 1.000 urine output 20.0 (6) poor 33.3 (10) poor 0.382 arterial blood gas 100 (30) excellent 100 (30) excellent blood culture 73.3 (22) fair 86.7 (26) good 0.333 central venous pressure 60.0 (3) weak 71.4 (4) fair 1.000 saturation central vein 0 (0) poor 37.5 (2) poor 0.209 central venous line (<60 minute) 7.1 (1) poor 13.3(2) poor 1.000 central venous line (>60 minute) 28.6 (4) poor 26.7 (4) poor 1.000 bolus fluid therapy 28.6 (8) poor 40 (13) poor 0.700 antibiotic therapy 60 (18) weak 60 (18) weak 1.000 vasopressor administration 40 (2) poor 100 (6) excellent 0.182 blood transfusion 0 (0) poor 50 (3) poor 0.229 inotrope administration 0 (0) poor 50 (3) poor 0.497 rapid sequence intubation 100 (7) excellent 100 (9) excellent o2 therapy 96.7 (29) excellent 100 (30) excellent 1.000 high flow o2 therapy 10 (3) poor 40 (12) poor 0.015 * based on likert scale: ≥ 90% as excellent, 80-90% good, 70-80% fair, 60-70% weak and < 60% poor. but it was in poor compliance with sepsis treatment protocols. due to normal oxygen saturation in a large proportion of septic patients, emergency residents did not order high flow oxygen for them, wrongly. kumar et al. evaluated 2731 patients with severe sepsis and septic shock in the united states and canada, and found out that administration of antibiotics in the first hour of admission can improve survival rate by 79.9%, whereas, as they observed, each one-hour delay in antibiotic administration can increase mortality rate by 7.9% (18). in addition, leibovici et al. demonstrated that antibiotic therapy in the first hour of presenting to ed can decrease mortality, significantly (19). in this study, intravenous fluid was properly administered for only 28.6% and 40% of patients before and after training. administration of vasopressors agent was significantly increased after training workshops and reached excellent level of compliance with protocol. an audit that evaluated protocol adherence regarding fluid therapy in management of septic children showed that in 62% of shocked cases, guideline was not followed (20). since severe sepsis and septic shock patients are usually critically ill and have a high mortality rate, their management in the crowded ed is usually accompanied by hazards. lack of fixed nursing and medical personnel for accurate and continuous monitoring of these patients, especially in the initial hours of arrival, worsens the situation. under this condition, inevitably, all or part of the necessary diagnostic or therapeutic measures will be missed. as can be seen, even holding workshops in this regard could not significantly improve the situation. in other words, the main problem might not be proper knowledge, and the key to solve this problem might be found in the practice phase. maybe more rapid disposition of these patients to intensive care unit or increasing the number of personnel and treatment equipment for these patients could be helpful. preparing standard and logical checklists and requiring in-charge physicians to adhere to these protocols may be of help in this regard. 5. limitations: it would have been better if by increasing sample size we could carry out sub-group analyses based on residency year, sex, type of shift, etc. 6. conclusion: based on the finding of the present study, there were fair (7080%) to poor (<60%) compliance with standard protocol regarding 64% and 55% of studied measures in management of severe sepsis and septic shock in pre and post training workshops, respectively. the protocol adherence for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow o2 delivery were disappointingly low in both pre and post training period. it seems training workshops and implementation of clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. alavi-moghaddam et al. 4 7. appendix 7.1. acknowledgements this article has been derived from dr. ali anvari’s student thesis to receive his specialist degree in emergency medicine from shahid beheshti university of medical sciences. authors would like to acknowledge all the emergency department staff of imam hossein hospital. 7.2. authors contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the 4 criteria of authorship recommended by the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. bone rc, balk ra, cerra fb, et al. definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. chest. 1992;101(6):1644-55. 2. tannehill d. treating severe sepsis & septic shock in 2012. journal of blood disorders & transfusion. 2013;2013. 3. morrell mr, micek st, kollef mh. the management of severe sepsis and septic shock. infectious disease clinics of north america. 2009;23(3):485-501. 4. stearns-kurosawa dj, osuchowski mf, valentine c, kurosawa s, remick dg. the pathogenesis of sepsis. annual review of pathology. 2011;6:19. 5. angus dc, linde-zwirble wt, lidicker j, clermont g, carcillo j, pinsky mr. epidemiology of severe sepsis in the united states: analysis of incidence, outcome, and associated costs of care. critical care medicinebaltimore-. 2001;29(7):1303-10. 6. martin gs, mannino dm, eaton s, moss m. the epidemiology of sepsis in the united states from 1979 through 2000. new england journal of medicine. 2003;348(16):1546-54. 7. bennett je, dolin r, blaser mj. principles and practice of infectious diseases: elsevier health sciences; 2014. 8. fauci as. harrison’s principles of internal medicine: mcgraw-hill, medical publishing division. 9. russell ja. management of sepsis. new england journal of medicine. 2006;355(16):1699-713. 10. vincent j-l, moreno r, takala j, et al. the sofa (sepsisrelated organ failure assessment) score to describe organ dysfunction/failure. intensive care medicine. 1996;22(7):707-10. 11. ferrer r, artigas a, levy mm, et al. improvement in process of care and outcome after a multicenter severe sepsis educational program in spain. jama. 2008;299(19):2294-303. 12. miller iii rr, dong l, nelson nc, et al. multicenter implementation of a severe sepsis and septic shock treatment bundle. american journal of respiratory and critical care medicine. 2013;188(1):77-82. 13. robson w, beavis s, spittle n. an audit of ward nursesâăź knowledge of sepsis. nursing in critical care. 2007;12(2):86-92. 14. dellinger rp, levy mm, rhodes a, et al. surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. intensive care medicine. 2013;39(2):165-228. 15. dellinger r, carlet j, masur h, et al. surviving sepsis campaign management guidelines committee: surviving sepsis campaign guidelines for management of severe sepsis and septic shock. crit care med. 2004;32(3):858-73. 16. dellinger rp, levy mm, carlet jm, et al. surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. intensive care medicine. 2008;34(1):17-60. 17. catenacci mh, king k. severe sepsis and septic shock: improving outcomes in the emergency department. emergency medicine clinics of north america. 2008;26(3):603-23. 18. kumar a, roberts d, wood ke, et al. duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. critical care medicine. 2006;34(6):1589-96. 19. leibovici l, shraga i, drucker m, konigsberger h, samra z, pitlik s. the benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. journal of internal medicine-oxford-. 1998;244:379-86. 20. inwald dp, tasker rc, peters mj, nadel s. emergency management of children with severe sepsis in the united kingdom: the results of the paediatric intensive care society sepsis audit. archives of disease in childhood. 2009;94(5):348-53. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e28 or i g i n a l re s e a rc h alveolar arterial gradient and respiratory index in predicting the outcome of covid-19 patients; a retrospective cross-sectional study abhishek singh1, kapil dev soni2∗, yudhyavir singh1, richa aggarwal2, vineeta venkateswaran1, mohd suhail ashar2, anjan trikha1 1. department of anaesthesiology, pain medicine & critical care, all india institute of medical sciences, new delhi, india. 2. department of critical and intensive care, jai prakash narayan apex trauma center, all india institute of medical sciences, new delhi, india. received: february 2022; accepted: march 2022; published online: 14 april 2022 abstract: introduction: alveolar arterial (a-a) oxygen gradient and respiratory index can be of immense help for the critical care physician in clinical decision making. this study aimed to evaluate the potential application of a-a oxygen gradient and respiratory index in predicting the survival of covid-19 patients in intensive care unit (icu). methods: this is a retrospective cross-sectional study involving 215 adult patients with covid-19 disease, admitted to the icu between 1st april 2020 and 30 june 2021. details regarding demographic variables, comorbidities, laboratory and arterial blood gas (abg) findings were recorded. alveolar-arterial gradient and respiratory index were calculated and tested as predictors of survival. results: the mean age of the patients was 51.92 years (65.6 % male). hypertension was the most common comorbidity and oxygen via non-rebreathing mask was the most common modality used at the time of icu admission. mortality was 28.37% and average length of stay was 12.84 days. patients who died were older (p=0.02), mostly male (p=0.017), had at least one comorbidity (p<0.001), and higher heart rate and respiratory rate (<0.001 and p=0.03, respectively), lower ph on arterial blood gas (abg) (p=0.002), higher fio2 requirement (p<0.001), and increased a-a oxygen gradient on admission compared to survivors. according to receiver operating characteristic (roc) curve analysis, a-a oxygen gradient and respiratory index were not sensitive or specific in predicting mortality in the studied patient subset. conclusion: a-a oxygen gradient and respiratory index calculated at time of admission to icu in patients with covid-19 were poor predictors of survival. keywords: covid-19; critical care; blood gas analyses; pulmonary gas exchange; respiratory system abnormalities cite this article as: singh a, soni kd, singh y, aggarwal r, venkateswaran v, ashar ms, trikha a. alveolar arterial gradient and respiratory index in predicting the outcome of covid-19 patients; a retrospective cross-sectional study. arch acad emerg med. 2022; 10(1): e28. https://doi.org/10.22037/aaem.v10i1.1543. 1. introduction coronavirus disease (covid-19) has posed a significant challenge to the healthcare systems worldwide. hospitals are overwhelmed with patients suffering from severe covid-19 infection with arterial hypoxemia progressing to acute respiratory distress syndrome (ards) requiring intensive care unit (icu) admission and invasive mechanical ventilation ∗corresponding author: kapil dev soni; department of critical and intensive care, jai prakash narayan apex trauma center, all india institute of medical sciences, new delhi, india. email: kdsoni111@gmail.com, orcid: http://orcid.org/0000-0003-1214-4119. (1). different studies have identified several risk factors associated with poor outcome in covid-19 patients. some researchers have even developed prognostic models using combinations of different risk factors with good performance (auc>0.8), but none of these studies included respiratory index (ri) and alveolar-arterial (a-a) oxygen gradient amongst the studied predictors (2-5). the pao2/ fio2 (p/f) ratio is widely used in clinical practice to predict disease outcome in critically ill patients but ri and a-a gradient has not been in much use. p/f ratio is a good measure of lung dysfunction as depicted by berlin criteria in ards (6). the elevated a-a oxygen gradient associated with hypoxemia is also a good indicator of ventilation/perfusion mismatch and intrapulmonary shunting (7). an editorial by tobin et al. titled this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. singh et al. 2 “basing respiratory management of covid-19 on physiological principles” has explained the importance of calculating a-a oxygen gradient in covid-19 patients. the text states that a-a oxygen gradient was more precisely able to appraise the pathophysiological basis of hypoxemia compared to the p/f ratio (8). a-a oxygen gradient can be easily derived from arterial oxygen and carbon dioxide pressures while ri can be derived from a-a gradient and arterial oxygen. previous studies have shown the application of a-a gradient in patients with community-acquired pneumonia as an indicator of disease severity and outcome (9, 10). therefore, in the present study, we investigated whether a-a oxygen gradient and ri could predict outcome in covid-19 patients admitted to intensive care unit. 2. methods 2.1. study design and setting the study was conducted in a dedicated covid-19 care centre of all india institute of medical sciences, new delhi. the retrospective data presented in the study is part of a project that was approved by the institute ethics committee (iec291/17.04.2020). the requirement for written informed consent from individual patients was waived due to the retrospective observational nature of the study. 2.2. participants the study included all adult patients (age > 18 years) with confirmed covid-19 infection (reverse-transcription polymerase-chain reaction (rt-pcr)-confirmed report for sars-cov2), admitted to the icu between 1st april 2020 and 30 june 2021 with available electronic medical records. all patients with incomplete or missing data with respect to demographics, comorbidities, vital signs, laboratory findings, arterial blood gas, and outcome were excluded from the study. 2.3. data gathering data were retrospectively collected using medical records and computerized patient record system. data collected included demographics (age, sex), vital parameters (heart rate, respiratory rate, blood pressure, temperature), comorbidities, type of oxygen support on admission, fio2 used, spo2 (oxygen saturation), arterial blood gas (abg) analysis, blood cell count, renal function tests, liver function test, duration of hospital stay, and outcome. 2.4. definitions a-a gradient was calculated using the following formula: aado2 = [(fio2) (atmospheric pressure – h2o pressure) – (paco2/r)] – pao2 standard values of atmospheric pressure (760 mmhg), h2o pressure (47 mmhg) and r (0.80) were considered for calculating the a-a gradient. the a-a oxygen gradient and ageadjusted a-a oxygen gradient were also calculated for each patient. since a-a oxygen gradient is dependent on age, the age-adjusted a-a gradient might be more accurate for detecting disease severity. the age-adjusted a-a oxygen gradient was calculated by subtracting the expected a-a oxygen gradient for age from the measured a-a oxygen gradient. the expected a-a oxygen gradient for age was derived using the following formula (age/4) + 4. respiratory index was calculated using the following formula: ri= a-a oxygen gradient /pao2. 2.5. outcome the primary outcome of our study was to determine whether a-a oxygen gradient and ri at the time of admission to icu could predict the outcome of covid-19 patients in the icu. 2.6. statistical analysis continuous variables were expressed as mean ± standard deviation (sd) and categorical variables as number (percentage). group comparison was performed using independent t-tests or chi-square tests. a receiver operating characteristic (roc) curve was made and area under the curve (auc) was calculated to assess an optimal cut-off value of the a-a oxygen gradient and ri. a p-value less than 0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of studied patients a total of 300 patients with confirmed covid-19 infection admitted to the icu during the study period were screened for possible inclusion in the study. two hundred eighty patients met the inclusion criteria. after excluding 65 patients due to missing or incomplete data, the final studied cohort consisted of 215 patients. these were subdivided into survivors and non-survivors as well as into mild, moderate, or severe ards based on p/f ratio. table 1 shows the patient’s demographics, comorbidities, vital signs, laboratory parameters, abg values, a-a oxygen gradient, and ri at time of admission to icu. the mean age of the patients was 51.92 ±13.89 years (65.6% male). 114 (53.3%) cases had at least one comorbidity. hypertension was the most common comorbidity (37.4%) followed by diabetes (26.2%), chronic kidney disease (10.3%), malignancy (5.6%), and tuberculosis (1.9%). mean vital signs on admission, namely heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, and oxygen saturation were 99.46 per minute, 127.97 mmhg, 78.10 mmhg, 24.26 per minute, and 94.89%, respectively. laboratory parameters were grossly normal except for slightly deranged renal and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e28 figure 1: receiver operating characteristic (roc) curve of alveolar arterial gradient (best cut-off = 0.28; area under the curve (auc) = 0.602) and respiratory index (best cut-off = 0.28; auc = 0.522) in predicting the mortality of covid-19 cases. liver functions. table 2 shows the modalities of oxygen therapy for studied cases. the most common oxygen therapy modality used at the time of icu admission was non-rebreathing mask (67.4%) followed by high-flow nasal cannula (hfnc) (10.7%), mechanical ventilation (9.8%), oxygen via face mask (5.6%), and non-invasive ventilation (niv ) (5.6%). arterial blood gas on admission showed a mean ph of 7.39, pco2 36.42 mmhg, po2 97.06 mmhg, p/f ratio 154.98, a-a gradient 314.07 mmhg, normal gradient for age 16.98 mmhg, ageadjusted a-a oxygen gradient 302.43 mmhg, and ri of 4.50. mortality rate was 28.37% and average length of stay was 12.84 days. 3.2. predictors of mortality subgroup analysis amongst survivors and non-survivors showed that non-survivors were older (p = 0.02), mostly male (p = 0.017), had at least one comorbidity (p = 0.001), and had higher heart rate and respiratory rate (p = 0.001 and p = 0.03, respectively) compared to survivors. they also had higher total leucocyte counts, higher values of serum urea, blood creatinine, bilirubin, liver enzymes and inr, and lower values of serum protein and albumin compared to survivors (table 1). the analysis of abg and oxygen therapy on admission showed that that non-survivors had lower ph (p = 0.002), higher fio2 requirement (p = 0.001), and increased a-a oxygen gradient (including calculated, normal gradient for age, and age-adjusted a-a oxygen gradient) on admission. a reduction in pao2 and increased a-a oxygen gradient were associated with presence of severe covid-19. however, there was no significant difference in the ri between survivors and non-survivors. after stratifying the patients into mild, moderate and severe ards based on p/f ratio, we found that an increased a-a gradient was associated with increased severity of ards (p = 0.001). patients with severe ards had higher oxygen requirement, increased a-a oxygen gradient, lower pao2, lower paco2, and higher ri compared to patients with mild or moderate ards. 3.3. predictive value of a-a gradient and ri figure 1 and table 3 show the roc curves of a-a oxygen gradient and ri in predicting the mortality of covid-19 cases. the area under the curve (auc), sensitivity, specificity, positive predictive value, and negative predictive value of a-a gradient in this regard were 0.602, 57%, 57%, 35%, and 77%, respectively. in addition, the auc, sensitivity, specificity, positive predictive value, and negative predictive value of ri in predicting the outcome of covid-19 cases were 0.522, 54%, 48%, 29%, and 73%, respectively. 4. discussion the present study found that a-a oxygen gradient and ri on admission are poor predictors for outcome in covid19 patients admitted to the icu. the a-a oxygen gradient is the measure of difference between oxygen level in the alveoli and arterial blood (8). it helps differentiate between hypoxemia due to dysfunction of alveolar capillary unit, in which a-a oxygen gradient is raised, or due to pump failure, in which the gradient is normal. data on prognostic utility of a-a oxygen gradient and ri in patients with covid19 are scarce at present. because of the effect of covid-19 disease on pulmonary gas exchange, shunting, and ventilation/perfusion ratio, we decided to evaluate the efficacy of aa oxygen gradient and ri in guiding critical care clinicians. various biomarkers have been shown to correlate with the clinical outcome in covid-19 patients (11, 12). however, most of them are timeand resourceintensive, while abg analysis is easily available in all critical care units and gives additional useful information on acid-base status, oxygenation, and ventilation status, amongst others. the relationship this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. singh et al. 4 table 1: demographic and clinical characteristics of covid-19 patients parameter overall (n-215) survivor (n-154) dead (n=61) p age ( year) 51.92 ±17.89 49.52 ±17.49 58.05 ±17.55 0.022 gender male 141 (65.6) 93 (60.4) 48 (78.7) 0.017 female 74 (34.4) 61(39.6) 13(21.3) length of stay mean ± sd 12.84 ± 9.31 13.50 ± 9.36 11.16 ± 9.05 0.097 comorbidities any type 114 (53.3) 71(46.4) 43 (70.5) 0.002 htn 80 (37.4) 52 (34) 28 (45.9) 0.142 dm 56 (26.2) 35 (22.9) 21 (34.4) o.118 ckd 22 (10.3) 13 (8.5) 9 (14.8) 0.266 malignancy 12 (5.6) 3 (1.9) 9 (14.8) 0.001 tb 4 (1.9) 2 (1.3) 2 (3.3) 0.68 vital signs fever °c 25 (11.6) 19 (13.4) 6 (9.8) 0.63 hr (/minutes) 99.46 ± 21.12 95.38 ± 18.71 109.43 ± 23.41 0.001 sbp (mmhg) 127.97 ± 21.89 127.36 ± 21.37 129.44 ± 23.22 0.53 dbp (mmhg) 78.10 ± 12.93 78.25 ± 12.23 77.75 ± 14.60 0.80 rr (/minute) 24.26 ± 5.62 23.64 ± 5.11 25.57 ± 6.44 0.03 sao2 (%) 94.89 ± 6.25 95.16 ± 5.34 94.21 ± 8.14 0.32 laboratory parameters hb (mg/dl) 11.00 ± 2.45 10.98 ± 2.39 11.04 ± 2.62 0.88 wbc (×103 ) 12.03 ± 8.07 11.28 ± 8.29 13.85 ± 7.27 0.03 plt (×103 ) 227.80 ± 194.01 237.46 ± 214.18 204.46 ± 131.91 0.26 urea (mg/dl) 59.81 ± 58.79 47.91 ± 35.80 89.37 ± 87.89 0.001 creatinine(mg/dl) 1.61 ± 2.58 1.40 ± 2.09 2.14 ± 3.48 0.06 sodium(meq/l) 134.52 ± 9.00 133.18 ± 7.61 137.34 ± 10.94 0.003 potassium(mmol/l) 4.23 ± 0.82 4.21 ± 0.76 4.26 ± 0.95 0.732 bilirubin(mg/dl) 1.32 ± 3.09 1.03 ± 1.51 2.06 ± 5.20 0.02 sgot(u/l) 173.54 ± 1122.61 71.16 ± 146.95 414.14 ± 2033.93 0.04 sgpt(u/l) 89.66 ± 210.40 58.38 ± 105.16 163.16 ± 340.57 0.001 tp(g/dl) 6.28 ± 0.99 6.36 ± 0.94 6.08 ± 1.10 0.064 albumin(g/dl) 2.83 ± 0.70 2.89 ± 0.70 2.69 ± 0.67 0.062 gb(g/dl) 3.44 ± 0.72 3.46 ± 0.69 3.37 ± 0.77 0.419 alp(u/l) 132.57 ± 239.35 137.66 ± 281.32 120.68 ± 81.06 0.647 inr 1.29 ± 0.60 1.21 ± 0.63 1.42 ± 0.53 0.04 aptt (second) 33.45 ± 26.22 33.88 ± 31.66 32.62 ± 9.34 0.774 abg parameters ph 7.39 ± 0.13 7.41 ± 0.09 7.35 ± 0.18 0.002 po2(mmhg) 97.06 ± 68.64 94.71 ± 66.58 102.99 ± 73.82 0.427 pco2(mmhg) 36.42 ± 9.87 36.12 ± 9.37 37.17 ± 11.06 0.483 fio2 0.64 ± 0.11 0.62 ± 0.10 0.69 ± 0.13 0.001 p/f ratio 151.99 ± 97.27 150.60 ± 91.97 155.51 ± 110.25 0.739 a-a gradient(mmhg) 316.72 ± 91.84 307.85 ± 79.88 339.13 ± 114.46 0.024 normal 16.98 ± 4.47 16.38 ± 4.37 18.51 ± 4.39 0.002 age-adjusted 301.14 ± 89.54 291.48 ± 80.28 326.16 ± 106.75 0.011 ri 4.50 ± 2.52 4.41 ± 2.33 4.73 ± 2.96 0.40 data are presents as mean ± standard deviation (sd) or number (%). htn: hypertension; dm: diabetes mellitus; ckd: chronic kidney disease; tb: tuberculosis; hr: heart rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; rr: respiratory rate; hb: haemoglobin; wbc: white blood cell; plt: platelet; sgot: serum glutamic-oxalo acetic transaminase; sgpt: serum glutamic-pyruvic transaminase; tp: total protein; gb: globulin; alp: alkaline phosphatase; inr: international normalized ratio; aptt: activated partial thromboplastin time; fio2: fraction of inspired oxygen; p/f ratio: ratio of arterial partial pressure of oxygen to inspired fractional concentration of oxygen; a-a gradient: alveolar arterial oxygen gradient; ri: respiratory index. between a-a gradient and outcome has already been demonstrated in patients with community acquired pneumonia (9, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e28 table 2: comparing the survival rate based on different respiratory supports mode overall (n-215) survived (n-154) died (n-61) p value face mask 12 (5.6) 10 (6.5) 2 (3.3) nrbm 145 (67.4) 120 (78.4) 25 (41.7) hfnc 23 (10.7) 14 (9.2) 9 (15.0) 0.001 niv 12 (5.6) 6 (3.9) 6 (10.0) mv 21 (9.8) 3 (2.0) 18 (30.0) data are presented as number (%). nrbm: non-rebreathing mask; hfnc: high-flow nasal cannula; niv: non-invasive ventilation; mv: mechanical ventilation. table 3: screening performance characteristics of a-a gradient and respiratory index in predicting the mortality of covid-19 patients character a-a gradient respiratory index normal age-adjusted sensitivity 0.57 0.52 0.54 specificity 0.57 0.62 0.48 ppv 0.35 0.35 0.29 npv 0.77 0.77 0.73 plr 1.32 1.36 1.03 nlr 0.75 0.77 0.95 auc (95%ci) 0.63(0.55-0.72) 0.58(0.48-0.67) 0.52(0.43-0.61) data are presented with 95% confidence interval in 0.28 cut-off point. a-a gradientalveolar arterial oxygen gradient; ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; auc: area under the receiver operating characteristic (roc) curve. 10, 13). avci et al. showed that a-a oxygen gradients were robust predictors of 30-day mortality in patients with community acquired pneumonia and demonstrated even better performance than inflammatory markers like crp or scores like psi or curb-65 (13). few studies have been published evaluating the predictive value of a-a oxygen gradient on admission as a tool for diagnosis, triage, clinical decision-making, or predicting outcome. gabrielli et al., in their retrospective study on relationship between alveolar-arterial oxygen gradient, mortality, and admission to intensive care unit in severe covid-19-related pneumonia, found that a-a o2 gradient, which was calculated for patients with severe covid19 on arrival to emergency department, was able to predict early admission to icu, but not mortality (14). similarly in our study, a-a gradient and ri were neither sensitive nor specific predictors of mortality in covid-19 patients in the icu. gupta et al., in their retrospective cohort study, found that alveolar-arterial oxygen gradient was a good predictor of mortality in covid-19 patients started on non-invasive ventilation (niv ) for increasing respiratory distress (15). it could be due to inclusion of patients with severe disease requiring niv, while our study included patients receiving oxygen from face mask to ventilator. carlino et al., in their observational study, demonstrated that patients admitted to icu have higher a-a gradients than non-icu patients, and that a-a gradient has good accuracy (auc of 0.952) in predicting icu admission in patients with covid-19 (16). de roos mp et al., in their retrospective analysis, showed that low dose chest computed tomography and a-a gradient may serve as rapid and accurate tools to diagnose covid-19 pneumonia and to select mildly symptomatic patients in need for hospitalization (17). secco et al., in their study, showed that a-a gradient and lung ultrasound are effective tools for bedside risk stratification of covid-19 patients when p/f ratio and clinical manifestations do not indicate severe lung dysfunction (18). in the present study, we also found that the predictors of poor prognosis were advanced age, male gender, presence of comorbidities, malignancy, raised heart rate and respiratory rate, increased total leucocyte counts, altered liver and renal function, lower ph, higher oxygen requirement, and increased a-a gradient. the reason for such result is multifactorial. it can be due to interplay of multiple factors like hypovolemia due to fever and reduced fluid intake, right or left ventricular dysfunction due to invasive mechanical ventilation with high positive end-expiratory pressure, myocarditis, pulmonary embolism, and vasodilation and increased capillary leak due to sepsis and cytokine storm. other reasons can be changing guidelines with respect to steroid therapy, antiviral therapy, and self proning, which may have affected the outcome. 5. limitations our study had several limitations. firstly, it was a retrospective single centre study with a number of missing variables and inevitable bias in identifying and recruiting pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. singh et al. 6 tients. secondly, causes of raised a-a oxygen gradient unrelated to covid-19, for instance pulmonary embolism, were not evaluated. thirdly, our study had a relatively small sample size of 215 patients, hence external validation of the findings is needed to warrant its clinical utility. 6. conclusion our study demonstrated that a-a oxygen gradient and respiratory index are not effective in predicting mortality among covid-19 patients in the icu. however, our findings need confirmation in well-designed studies with large numbers of patients. 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions a.s, k.d.s, r.a, y.s, m.s.a , v.v, a.t -contributed to conception, study design, and data collection and evaluation. a.s and kdscontributed to statistical analysis, and interpretation of data a.s, y.s, at; drafted the manuscript, which was revised by k.d.s. all authors read and approved the final manuscript. 7.3. funding and supports none. 7.4. conflict of interest none. references 1. poston jt, patel bk, davis am. management of critically ill adults with covid-19. jama. 2020;323(18):1839-41. 2. zheng z, peng f, xu b, zhao j, liu h, peng j, et al. risk factors of critical & mortal covid-19 cases: a systematic literature review and meta-analysis. j infect. 2020;81(2):e16-e25. 3. liang w, liang h, ou l, chen b, chen a, li c, et al. development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with covid-19. jama intern med. 2020;180(8):1081-9. 4. dong y-m, sun j, li y-x, chen q, liu q-q, sun z, et 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rashid ao, ismail m, khan ma, et al. alveolar–arterial oxygen gradient, pneumonia severity index and outcomes in patients hospitalized with community acquired pneumonia. clin exp pharmacol physiol. 2008;35(9):1032-7. 10. shin jb, lee wj, park jh, choi sp, jung sk, woo sh. the prognostic value of alveolar-arterial oxygen gradient for community-acquired pneumonia in the ed. j korean soc emerg med. 2013;24(5):571-8. 11. petrilli cm, jones sa, yang j, rajagopalan h, o’donnell l, chernyak y, et al. factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in new york city: prospective cohort study. bmj. 2020;369:m1966. 12. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. lancet. 2020;395(10229):1054-62. 13. avci s, perincek g. the alveolar-arterial gradient, pneumonia severity scores and inflammatory markers to predict 30-day mortality in pneumonia. am j emerg med. 2020;38(9):1796-801. 14. gabrielli m, esperide a, valletta f, giancristofaro f, santoro m, santarelli l, et al. relationship between arterial-alveolar oxygen gradient, mortality and admission to intensive care unit in severe covid-19 related pneumonia-a pilot study. biomed j sci tech res. 2020;31(1):23864-9. 15. gupta b, jain g, chandrakar s, gupta n, agarwal a. arterial blood gas as a predictor of mortality in covid pneumonia patients initiated on noninvasive mechanical ventilation: a retrospective analysis. indian j crit care med. 2021;25(8):866. 16. carlino mv, valenti n, cesaro f, costanzo a, cristiano g, guarino m, et al. predictors of intensive care unit admission in patients with coronavirus disease 2019 (covid19). monaldi arch chest dis. 2020;90(3):1410. 17. de roos mp, kilsdonk id, hekking p-pw, peringa j, dijkstra ng, kunst pw, et al. chest computed tomography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e28 and alveolar–arterial oxygen gradient as rapid tools to diagnose and triage mildly symptomatic covid-19 pneumonia patients. erj open res. 2021;7(1):00737-2020. 18. secco g, salinaro f, bellazzi c, la salvia m, delorenzo m, zattera c, et al. can alveolar-arterial difference and lung ultrasound help the clinical decision making in patients with covid-19? diagnostics. 2021;11(5):761. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e66 rev i ew art i c l e aluminum phosphide poisoning mortality rate in iran; a systematic review and meta-analysis farhad bagherian1, navid kalani2, fatemeh rahmanian3, samaneh abiri3, naser hatami4, mahdi foroughian5, neema john mehramiz6, behzad shahi7∗ 1 department of emergency medicine, babol university of medical sciences, babol, iran. 2 research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. 3 department of emergency medicine, jahrom university of medical sciences, jahrom, iran. 4 student research committee, jahrom university of medical sciences, jahrom, iran. 5 department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 6 department of psychiatry neurology, banner university medical center, tucson, az, usa. 7 department of emergency medicine, faculty of medicine, zahedan university of medical sciences, zahedan, iran. received: september 2021; accepted: september 2021; published online: 3 october 2021 abstract: introduction: according to statistics provided by the forensic medicine facility of iran, there are a high number of aluminum phosphide (alp) poisoning-related deaths in the country; while the mortality rate varies in different studies. this study aimed to determine a pooled estimate of alp poisoning mortality rate in iran. methods: the present study was a systematic review and meta-analysis of the mortality rate of alp poisoning in iran. through the quarry of persian and english databases, using “aluminum phosphide”, “phosphine”, “rice pills”, “poisoning”, and “iran” as keywords, and no time restrictions, studies reporting mortality rate in alp poisoning cases were collected. the random-effects model was used to pool the proportions of mortality and age of survivors versus non-survivors. results: 21 studies with 3432 cases of alp poisoning were included in this meta-analysis. the pooled mortality rate of alp poisoning in iran was 39.6%, (95% ci: 31.5%-47.9%; i2 = 95%). since there was significant publication bias, the trim-and-fill correction was conducted and the corrected pooled mortality rate was estimated to be 27.3% (95% ci: 18.9%36.5%), which is the rate that should be considered for clinical guidance. morality rate in male and female patients was 62.3% (95% ci: 53.5%-70.8%) and 37.7% (95% ci: 29.2%-46.5%), respectively (p < 0.01). survivors had significantly lower mean age than non-survivors (smd: -0.26 (95% ci: -0.37 to -0.15); p < 0.01; i2=0%). conclusion: according to this report, the mortality rate of alp poisoning in iranian population is about 27%, with men having a higher fatality rate than women. poisoning at a younger age is associated with better results. keywords: aluminum phosphide; poisoning; phosphine; mortality; iran cite this article as: bagherian f, kalani n, rahmanian f, abiri s, hatami n, foroughian m, john mehramiz n, shahi b. aluminum phosphide poisoning mortality rate in iran; a systematic review and meta-analysis. arch acad emerg med. 2021; 9(1): e66. https://doi.org/10.22037/aaem.v9i1.1396. 1. introduction aluminum phosphide (alp), known as rice pill in iran, is a very effective pesticide for commercial and industrial use. the high lethality of alp is due to phosphine gas (ph3), ∗corresponding author: behzad shahi; department of emergency medicine, faculty of medicine, zahedan university of medical sciences, zahedan, iran. email: mr.shahi87@yahoo.com, tel: 09151913501, orcid: http://orcid.org/0000-0001-9884-1542. which is released when alp reacts with water. the resulting gas is colorless and has a distinct odor of garlic or rotten fish (1). phosphine gas released in the stomach of individuals who have devoured this pill intentionally or accidentally, quickly gets absorbed into body organs and disrupts enzymatic activities, causes cell death and disrupts the function of almost all vital organs, namely brain, lungs, and liver (2). symptoms of poisoning are due to the involvement of the cardiovascular, gastrointestinal, nervous, and pulmonary systems. the most common clinical signs and sympthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. bagherian et al. 2 toms of alp poisoning are restlessness, irritability, dizziness, vertigo, tremors, diplopia, imbalance, cough, shortness of breath, abdominal colic, nausea, vomiting, in some cases black vomit, black stools, decreased cardiac output, irregular heartbeat, pulmonary edema, cyanosis, renal impairment, jaundice, enlarged liver and spleen, intestinal paralysis, seizure, and acute respiratory distress syndrome (1). severe hypotension and shock are the most common symptoms of severe poisoning (3). delayed symptoms of intoxication include pulmonary edema, hypocalcemic tetany, cardiovascular arrhythmia, liver damage, bradycardia, metabolic acidosis, thrombocytopenia, and methemoglobinemia (4). treatment for alp poisoning is only supportive treatment, as there is no known antidote available against it. the effectiveness of these treatments in poisoned patients depends entirely on the degree of poisoning and the time of arrival at the medical center; the mortality rate following alp poisoning varies between different studies. despite the ban on the public sale of rice pills since 2012, iran has a high number of alp poisoning cases (intentional or accidental). according to statistics provided by the forensic medicine facility of iran, there is a high number of alp poisoning-related deaths in the country (5). while many observational studies have reported the cases of alp poisoning; there is no overall view about the mortality rate of alp poisoning in the country. this study aimed to determine a pooled estimate of the alp poisoning mortality rate in iran. 2. methods 2.1. study design and setting the present study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist. scientific sources were searched by two independent researchers from 2000 to 2021. search for articles and dissertations in iranian sources were performed in the university jihad scientific information center (sid) database, and pubmed / medline, scopus, embase, and web of science databases with the keywords of “aluminum phosphide”, “phosphine”, “rice pills”, “poisoning”, and “iran”. english and persian articles were quarried. the reference list of all articles identified in the early stages was reviewed in order to access cited articles that were not found via electronic searches. the studies that reported cases of aluminum phosphide poisoning in iran were selected in two stages. first, the abstracts of articles obtained in electronic searches were thoroughly reviewed, and irrelevant or duplicate studies were eliminated. in the second stage, the decision on the final inclusion of studies was made after reviewing the full text of the studies (table 1). information on study characteristics, quality, and results were extracted from each selected article. the criteria for inclusion in the study was to evaluate patients with aluminum phosphide poisoning and present their mortality rate. studies that only looked at the decedents were not included in this study. all articles that met the selection criteria were evaluated in terms of methodological quality. the newcastle-ottawa score (nos) was used to evaluate the quality of the meta-included papers. nos included three sections (case selection, group comparison, and exposure determination) and eight elements. the quality rating scale went from 0 (worst) to 9 (highest) (best). studies with a score higher than 5 were included. 2.2. data extraction a pilot evaluation of the final full texts was performed to ensure inclusion of all data needed for final data synthesis to answer the study questions. based on this evaluation, a checklist was provided for data extraction. this checklist included study id, study design, province of study, duration of observation, the total number of cases (n), number of male and female cases, total mortality rate and mortality rate in each gender, and mean age of all participants, survivors, and non-survivors. a checklist of each study was filled by a single reviewer. randomly, 5 studies were refilled by a second reviewer to ensure inter-rater reliability of checklists. 2.3. data synthesis we quantitatively examined the mortality rates of aluminum phosphide poisoning, the gender ratio of mortality, and the age of individuals. mean age was pooled using the random effect model through calculation of standard mean difference (smd). the possibility of publication bias was checked using freeman-tukey double arcsine transformation and egger’s test in case of the binomial outcome of mortality. in case of publication bias, the trim-and-fill approach was used to address the issue. all statistical analyzes were performed using r statistical packages. 3. results as shown in the prisma flowchart (figure 1), finally, 21 studies with 3432 cases of alp poisoning were included in this meta-analysis. there were about 1637 male and 1732 female poisoning cases (one study, shadnia et al., 2007, did not report gender). cases were evaluated from 2000 to 2021 (table 1). 3.1. overall mortality rate the pooled mortality rate of alp poisoning in iran was 39.6% (95% ci: 31.5% to 47.9%); with 95% heterogeneity (p <0.01; figure 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e66 table 1: studies included in the meta-analysis study* id year** n gender (n) age (year; mean ± sd) male female total survivor died majidi et al., 2021; (6); urmia 20152019 134 96 38 40 28.6±11.5 na na navabi et al. 2018 (7); kermanshah 20142015 77 48 29 41 na 28.7±10.2 31.3±10.7 shadnia et al., 2007 (8);tehran 2003 63 na na 8 na na na ataei et al., 2021 (9);mashhad 20192021 41 23 18 8 27.56±7.09 na na mehrpour et al., 2008(10); tehran 2006 45 24 21 32 27.3 ± 11.5 na na rahbar et al., 2006 (11);rasht 20002003 116 63 53 68 29.47±14.79 na na montazer et al., 2016 (12);sari 2013-2014 52 14 38 16 23.4±9.2 na na rahbar et al., 2013 (13);rasht 2008-2009 104 66 38 93 33.8±14.69 na na rahbar et al., 2011 (14);rasht 2005-2006 102 68 34 77 29.75±14.34 na na soltaninejad et al. 2012 (15);tehran 20072010 956 433 523 230 na 24.5±8.19 27.32±11.31 hassanian-moghaddam et al. 2007 (16);tehran 2005-2007 340 162 178 100 25.7± 9.2 na na hosseinian et al., 2011 (17); mazandaran 20072008 102 46 56 19 28.5±12.4 28.66±12.75 24.92±9.51 shokrzadeh et al., 2017(18);gorgan 20082015 53 37 16 16 na na na farzaneh et al., 2015 (19);ardabil 2006-2012 386 72 314 95 na na na navabi et al., 2018 (7);kermanshah 20142015 118 75 43 41 na 28.7±10.2 31.3±10.7 shadnia et al., 2009 (20);tehran 20002007 471 246 225 146 na 24.38 ± 8.81 30.87 ± 14.80 mehrpour et al., 2009 (21);tehran 20062007 45 24 21 32 na na na erfantalab et al., 2017 (22);tehran 2014 2015 39 27 12 15 31.0±11.3 30.5±11.7 (17–65) 31.8±11.1 (23–61) mostafazadeh et al., 2011 (23) tehran 2009 48 24 24 9 25.5±9.5 na na tavakoli-far et al., 2018 (24);karaj 20062011 67 36 31 30 na na na shayeste et al., 2017 (25);gorgan 20092016 73 53 20 25 27.47±16.75 na na * all study types were cross-sectional. ** duration of observation. na, not addressed. 3.2. gender and mortality rate the male and female mortality rates were pooled from 12 studies listed in figure 3a and 3b. proportion of morality in male patients was 62.3% (95% ci: 53.5% to 70.8%); with 80% heterogeneity (p < 0.01). the proportion of mortality in female patients was 37.7% (95% ci: 29.2% to 46.5%); with 80% heterogeneity (p < 0.01). as shown in the funnel plot in figure 4. freeman-tukey double arcsine transformation and egger’s test revealed significant funnel plot asymmetry, indicating the possibility of publication bias or small-study effects, p<0.01. it reveals that studies are shifted to the right. linear regression test of funnel plot asymmetry also confirmed asymmetry (t = 2.23, df = 21, p = 0.0369). to address the publication bias, we utilized the trim-and-fill approach to look at the effect on the pooled estimate. after applying the trim-and-fill approach to account for missing studies, the result was a symmetrical egger funnel plot, which is shown in figure 5, where the linear regression test of funnel plot asymmetry was not significant (t = 0.17, df = 25, p = 0.8673). the mortality rate that should be considered for therapeutic purposes is 27.3% (95% ci: 18.9% to 36.5%) as shown in the new forest plot in figure 6, with the pooled proportion corrected for publication bias. 3.3. mean age and mortality rate in a comparison of mean age of survivors versus nonsurvivors, a random effect model showed a significant difference between survivors versus non-survivors, where survivors had significantly lower age (smd: -0.26, 95% ci: -0.37 to -0.15; p< 0.01; figure 7). heterogeneity was not observed in the case of age comparison (i2=0%). 4. discussion this study showed a mortality rate of about 40% along with a publication bias. when we used trim-and-fill correction, mortality rate decreased to about 27%, which seems to be far from the reality. there is no proper official data available to facilitate reaching a final decision on mortality rate and in our knowledge, and this is the first study in iran giving a comprehensive mortality rate for alp poisoning. also, there is a wide distance between the mortality rates of males and females, and averaging to find the overall mortality rate of alp poisoning does not seem reliable. other studies have reported a 70–100% mortality rate, as reviewed by meena et al. (26). a 59.3% mortality rate was reported in mathai and bhanu study in 2010 (27). but iranian studies have reported a wider range of mortality rates as abdollahi and mehrpour (28) reported the mortality rate to vary this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. bagherian et al. 4 from 30 to 100%. but other factors, as well as the amount of consumed alp, affect the results. unfortunately, due to factors such as high toxicity and high lethality of this substance and ease of access to this toxin, based on official reports a relatively high rate of poisoning is seen in the country, especially in some provinces such as tehran, gilan, mazandaran, golestan, and lorestan, (5). our meta-analysis also showed that most published studies are performed in these provinces. our study showed that the mortality rate of alp poisoning in iran was 39.6% with the proportion mortality being 62.3% in males and 37.7% in female patients. in the comparison of mean age of survivors versus non-survivors, there was a significant difference between survivors versus non-survivors, where survivors had a significantly lower age. based on the reports by forensic medicine facility of iran, most of the alp-poisoning-related deaths were in the age group of 20-40 years, and most of them intended to commit suicide. statistics from 2008 to 2011 show that death from rice pills were on the rise. there were 214 individual cases of mortality (105 women / 109 men) in 2008, 228 cases (104 women / 124 men) in 2009, 406 cases (202 women / 204 men) in 2010, and 463 cases (204 women / 259 men) in 2011 (5). in a comparison of studies performed outside iran, according to el-sarnagawy’s study, there was a strong link between mortality risk and young age, rural location, suicidal ingestion, increased toxic dose, and prehospitalization duration. they reported 44.7% deaths with alp in 5 years (29). a study by sheta showed that 43.3 percent of cases died (30). compared to our study, better survival in iranian poisoning cases could be due to the higher experience of iranian health care providers in the management of alp poisoning, as most case reports of successful treatment of alp are being published by iranians (31-33). in a study by alnasser et al., they evaluated alp poisoning in saudi arabia over a nine-year period, the highest rate of death from alp poisoning belonged to children, and it occurred most frequently during household fumigation. delays in medical treatment and diagnosis may have had a role in the patients’ death (34). poisoning due to the use of rice pills in iran has led to the responsible organizations and institutions in the country taking measures to ban the import and restrict the sale of rice pills. having comprehensive data on alp poisoning mortality rate in our country could help us in policymaking regarding public sale of alp for industrial purposes. 5. limitations a concern in this study was the possibility of publication bias. as a result, the findings of this study should be interpreted with caution, bearing the limitations in mind. although our article search was limited to iran, there was a low possibility of biased study retrieval due to the high number of studies; however, there might be a possibility of incomplete study retrieval as we did not find studies performed in the south of the country and medical dissertations and official and unofficial reports were not included. reporting bias might also have affected our results as datasets with high mortality rates might have not be reported. 6. conclusion according to this report, the mortality rate of alp poisoning in iranian population is about 27%, with men having a higher fatality rate than women. poisoning at a younger age is associated with better results. 7. declarations 7.1. acknowledgments we would like to thank the clinical research development unit of peymanieh educational and research and therapeutic center of jahrom university of medical sciences for providing facilities for this work. 7.2. funding this research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 7.3. conflict of interest statement the authors have declared that no competing interests exist. 7.4. author contribution fb and nk conceptualized the study questions and performed revisions. fr and sa performed the searches. nh and njm conducted the statistical analyses. other authors provided the draft manuscript. 7.5. ethical considerations all ethical principles are considered in this article. references 1. cienki j. non-anticoagulant rodenticides. clinical toxicology philadelphia, pa: wb saunders. 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soltaninejad k, shadnia s, zamani n, hassanian-moghaddam h, mahdavinejad a, et al. trend of blood lactate level in acute aluminum phosphide poisoning. world journal of emergency medicine. 2017;8(2):116. 23. mostafazadeh b, pajoumand a, farzaneh e, aghabiklooei a, rasouli mr. blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome. journal of medical toxicology. 2011;7(1):40-3. 24. tavakoli-far b, mahdi navesi b, salehi t, hosseini a, rahimzadeh m, dehghan-tarzjani mh, et al. to investigate the abundance of aluminum phosphide poisoning in karaj-iran from 2006 to 2011. alborz university medical journal. 2018;7(3):207-12. 25. shayeste y jalilian j ,haji mohammadi a, delaram a. a survey on the pattern of aluminum phosphide poisoning in gorgan, north of iran. beyhagh, 2017, 21(4) 55-64. 26. meena mc, mittal s, rani y. fatal aluminium phosphide poisoning. interdisciplinary toxicology. 2015;8(2):65. 27. mathai a, bhanu ms. acute aluminium phosphide poisoning: can we predict mortality? indian journal of anaesthesia. 2010;54(4):302. 28. wexler p. encyclopedia of toxicology: elsevier/academic press; 2014. 29. el-sarnagawy g. predictive factors of mortality in acute aluminum phosphide poisoning: 5 years retrospective study in tanta poison control unit. ain shams journal of forensic medicine and clinical toxicology. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. bagherian et al. 6 2017;29(2):70-9. 30. sheta aa, el-banna as, abd elmeguid r, mohamed he, gad nh. a study of the predictive factors of mortality in acute poisoning with aluminum phosphide with special reference to echocardiography and sofa score. environmental science and pollution research. 2019;26(32):33135-45. 31. hossien m, zohoorian p, foroughian m, awli sh, teimouri a. successful treatment of acute aluminum phosphide poisoning: possible benefit of olive oila case report. updates in emergency medicine. 2021;1(1):6-10. 32. shakeri m, soroosh d, shakeri h, kalani n, hatami n, foroughian m. successful treatment of acute aluminum phosphide poisoning by aloe vera syrup: a case report. international journal of medical toxicology and forensic medicine. 2021;11(2):e33016. 33. hassanian-moghaddam h, zamani n, rahimi m, hajesmaeili m, taherkhani m, sadeghi r. successful treatment of aluminium phosphide poisoning by extracorporeal membrane oxygenation. basic & clinical pharmacology & toxicology. 2016;118(3):243-6. 34. alnasser s, hussain sm, kirdi ts, ahmed a. aluminum phosphide poisoning in saudi arabia over a nine-year period. annals of saudi medicine. 2018;38(4):277-83. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e66 figure 1: prisma flow chart of study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. bagherian et al. 8 figure 2: forest plot of mortality rate. figure 3: forest plot of mortality rate based on gender, (a) male, (b) female. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e66 figure 4: funnel plot of included studies. figure 5: trim-and-fill corrected funnel plot of included studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. bagherian et al. 10 figure 6: trim-and-fill corrected forest plot of mortality rate. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e66 figure 7: forest plot of mean age of survivors versus non-survivors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e46 or i g i n a l re s e a rc h comparing the clinical characteristics, laboratory findings, and outcomes between epidemic and episodic methanol poisoning referrals; a cross-sectional study mehdi hadipourzadeh1, sara ebrahimi2, pardis ziaeefar2, nasim zamani1,3, hassan falahaty4, darren robert5,6, hossein hassanian-moghaddam1,3∗ 1. department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. social determinants of health research center, shahid beheshti university of medical sciences, tehran, iran. 4. loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 5. departments of clinical pharmacology and toxicology, and renal medicine and transplantation, st vincent’s hospital, sydney, australia. 6. st vincent’s clinical school, university of new south wales, sydney, australia received: april 2021; accepted: may 2021; published online: 12 june 2021 abstract: introduction: due to illegal manufacturing and sales of alcoholic beverages, epidemic outbreaks of methanol poisoning may occur. the aim of this study was to determine if there were differences in the severity, course of poisoning, and outcomes between methanol-poisoned patients admitted during an outbreak versus those who were admitted following episodic exposures. methods: the present retrospective study was performed in a single referral poisoning center between march 2018 and march 2019 in patients with confirmed methanol poisoning. during this time, in addition to episodic cases of methanol intoxication, there were three methanol poisoning outbreaks. outbreaks were characterized by an unexpected increase in the number of methanolpoisoned patients in a short period of time, which impacted resources and decision-making. the two groups were compared regarding their severity of poisoning, sessions of hemodialysis, and clinical outcomes. results: outbreak cases had a higher level of methanol than episodic cases. odds of being dialyzed more than once was 5.4 times higher in the cases presenting during an outbreak (95% ci 2.1-14.0; p=0.001). mean hospital stay, intubation/mechanical ventilation, and death were similar between the two groups. an evaluation of the alcoholic beverage samples available in the iranian black market during the outbreak showed a 7-percent methanol concentration with no ethanol content. conclusion: poisoning risk may be higher during methanol outbreaks due to the higher methanol concentrations, requiring more hemodialysis sessions for persistent metabolic acidosis. in addition to alcohol dehydrogenase blockade, careful risk assessment of all methanol poisonings can assist with stratifying the priority for, and duration of, hemodialysis to optimize outcomes. keywords: methanol; poisoning; disease outbreaks; renal dialysis; formaldehyde poisoning cite this article as: hadipourzadeh m, ebrahimi s, ziaeefar p, zamani n, falahaty h, robert d, hassanian-moghaddam h. comparing the clinical characteristics, laboratory findings, and outcomes between epidemic and episodic methanol poisoning referrals; a cross-sectional study. arch acad emerg med. 2021; 9(1): e46. https://doi.org/10.22037/aaem.v9i1.1278. ∗corresponding author: hossein hassanian-moghaddam; department of clinical toxicology, loghman-hakim hospital poison center, south karegar avenue, tehran, iran. tel/fax: +982155424041 email: hassanian@sbmu.ac.ir, hasanian2000@yahoo.com, orcid: https://orcid.org/0000-0003-4370-0544. 1. introduction methanol is a colorless and clear liquid used in industrial solvents, antifreeze solutions, and glass cleaners. pure methanol does not have a specific smell and it is tasteless. worldwide, methanol poisoning is largely due to consumption of illegal homemade alcoholic beverages (1, 2). less commonly, methanol poisoning may be the result of intentional consumption for suicidal intent. it is rapidly abthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hadipourzadeh et al. 2 sorbed post-ingestion and reaches its maximum concentration within 30 to 60 minutes with a minimal lethal dose of about 1 mg/kg of body weight in adults (1). metabolism of methanol to formic acid and formaldehyde results in toxicity and its clinical and laboratory manifestations (1). methanol poisoning is a medical emergency with signs/symptoms including weakness, blurred vision, nausea, vomiting, epigastric pain, headache, dyspnea, and cyanosis as well as central nervous system signs and symptoms including stupor, coma, convulsions, hypothermia, and death, particularly following a high dose of methanol and delayed treatment. factors playing a role in the delay in receiving effective medical care are fear of punishment in countries where alcohol consumption is illegal, nonspecific signs and symptoms in the early hours of intoxication, and limited knowledge of methanol intoxication by clinicians (3). risk factors that predict poor outcome in methanol intoxication include severe metabolic acidosis (blood ph< 7), lack of respiratory compensation, and coma (glasgow coma scale (gcs) <8) on admission (4). if a high dose of methanol has been consumed, the mainstay of treatment is alcohol dehydrogenase (adh) inhibition and hemodialysis (hd) to remove both methanol and its toxic metabolite, formic acid. methanol poisoning outbreaks have occurred in iran several times (5-7). acute methanol intoxication continues to be an important public health concern in many islamic countries such as iran, indonesia, malaysia, tunisia and turkey. it is anticipated that clinical outcomes may be worse in patients presenting during an outbreak due to resources being overwhelmed (2). however, during an outbreak it is also possible that patients may present to hospital and be diagnosed and treated earlier due to increased awareness, leading to more favorable outcomes (7). this study was designed to determine if there are differences in the severity, treatment, and outcome of poisoning between methanolpoisoned patients who present during an outbreak and those who are admitted as episodic cases of this intoxication. 2. methods 2.1. study settings and design this retrospective, descriptive study was conducted in a single large regional referral poisoning center during a oneyear period between march 2018 and march 2019. the study was approved by the ethics committee in shahid beheshti university of medical sciences (ethics committee no: ir.sbmu.retech.rec.1399.302). the need for informed written consent was waived because of the emergent nature of hd in the patients with signs and symptoms of severe methanol poisoning and since this was a retrospective study. 2.2. participants all patients who had consumed illicit alcoholic beverages, based on the history taken from the patient, or the relatives of critically ill patients, regardless of the presenting signs and symptoms were identified based on discharged international classification of disease (icd) 10 coding and an internal database that recorded all poisoned patients who received hemodialysis. the patient’s signs and symptoms of poisoning and their venous blood gas (vbg) analysis were assessed on admission. serum methanol concentration was measured when possible to confirm the exposure. the diagnosis of methanol poisoning was based on (i) a serum methanol level >6.25 mmol/l (20 mg/dl), or (ii) a clinical picture of methanol poisoning (abdominal pain, visual disturbances, dyspnea, central nervous system signs/symptoms) with both ph < 7.3 and serum bicarbonate < 20 mmol/l (8, 9). patients with methanol poisoning were treated with oral ethanol in a fixed dosing regimen using 1 ml/kg of five-fold diluted alcohol 96% and a maintenance dose of 0.16 ml/kg/h based on a national guideline (1). due to limited resources, ethanol blood concentrations could not be routinely and regularly measured in all patients. all patients who received hemodialysis (hd) were included in this study. indications for hd included significant metabolic acidemia (ph < 7.25 and/or bicarbonate < 15 mmol/l) with or without visual disturbances, electrolyte imbalance unresponsive to conventional therapy, and/or a serum methanol concentration > 6.25 mmol/l (20 mg/dl; the assay was intermittently available) (10). patients who had initial normal analyses but developed signs and symptoms of poisoning and metabolic acidosis in the following hours were treated with hemodialysis. those who died before the initiation of hd were excluded. hd was generally started between 30 minutes and eight hours after the decision was made to initiate it, depending on resource availability at the time. based on an existing definition of a methanol poisoning outbreak, an unexpected increase in number of cases of methanol intoxication (a minimum number of three cases within a few days to a few weeks) (2), we categorized the patients into two groups: outbreak and episodic cases. the outbreak group consisted of patients who had presented to our unit during the methanol toxicity outbreaks (two between september-november 2018 and one in march-april 2019). patients presenting to our unit at other times during the one-year study period were classified as episodic cases. first, 4-hour hd was performed for every patient with a history of alcohol ingestion based on the vbg on admission or symptoms of severe intoxication including visual disturbances, seizure, and loss of consciousness. if metabolic acidosis did not resolve after the first session of hd, particularly if visual disturbances were present, a second, and even third hd session was performed. persistence of visual disturthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e46 bances without acidemia was considered a sequelae and no hd was performed in this context. 2.3. data gathering patients’ demographic characteristics including age, gender, amount of alcohol consumption (in ml), time elapsed between consumption and hospital presentation, clinical features on admission including signs, symptoms, glasgow coma scale (gcs), and vital signs were recorded. results of routine lab tests including serial vbg analyses, the number of hd sessions required per patients and indications for repeated hd, requirement for intubation, duration of hospital stay, and the final outcome (death, complete recovery, or recovery with neurologic/ophthalmologic sequelae) were recorded. samples of the alcohol beverage were analyzed for the presence of methanol and ethanol on a random community sampling during outbreaks. 2.4. statistical analysis data was compared between the two groups using statistical package for social sciences (spss) software version 21 by application of chi-square and mann-whitney u test, with a significance threshold of p<0.05. spearman rank correlation coefficient test was used to measure the strength and direction of association between two continuous variables. enter logistic model was used to determine independent variables predicting repetition of dialysis or presentation during an outbreak in these patients. 3. results 3.1. baseline characteristics of studied cases during the study period, 157 patients were hospitalized due to methanol poisoning. figure 1 shows the timeline of referral cases indicating 3 outbreaks during the study period. three patients died before initiation of hd. all other patients required hd, including twelve patients with a normal admission vbg and no noticeable symptoms, but subsequent vbg analyses during hospitalization showed metabolic acidosis so they were treated using hd. in total, 154 methanolpoisoned patients received hd and were included in the study (figure 2; patient inclusion chart). the mean age was 31.9 ± 10.2 (range, 17 to 70) years, of whom 66 of the participants were classified as episodic cases and 88 were classified as outbreak cases. there was no statistically significant difference between these two groups in terms of the amount of the alcohol consumed and presenting signs and symptoms (table 1). however, there was a trend of delayed presentation in outbreak cases who presented after 35 hours, compared to episodic cases who had referred after 24 hours (p =0.802). the most common signs and symptoms were blurred vision (81.8%) and gastrointestinal symptoms including vomiting (51.9%) and nausea (49. 1%). the outbreak group had a statistically higher diastolic blood pressure (p =0.005) and respiratory rate (p =0.027), and lower temperature (p =0.004) at the time of admission but the differences were not clinically significant (table 1). 3.2. laboratory findings laboratory testing revealed that serum methanol levels were considerably higher in the outbreak group compared to the episodic group (n=130; p = 0.011) with median (interquartile range; iqr) concentration of 11.20 mg/dl (0, 30.6) (range 0, 80.5) and 0 (0, 13.8) mg/dl (range 0, 56.5) in outbreak and episodic groups, respectively. no significant difference was detected in the admission ph, pco2, and hco3 of vbg analyses between the two groups. of note, lactate dehydrogenase (ldh) was lower in outbreak group (table 2). there was a significant correlation between ldh and admission ph (r=-0.231, p=0.011), hco3 (r=-0.252, p=0.005), blood sugar (r=0.240, p=0.008), creatinine (r=0.272, p=0.002), serum potassium (r=0.297, p=0.001), and creatine kinase (r=0.205, p=0.025) on univariate analysis for the combined population. 3.3. outcomes eight patients were intubated during hospitalization (six in the outbreak and two in the episodic group, which was a nonsignificant difference). more patients in the outbreak group required more than one hd treatment session (35%), compared to the episodic group (9.1%) (table 3). of these, 117 were dialyzed only once (57 (64.8%) in outbreak group and 60 (90.9%) in episodic group), 32 were dialyzed twice and seven patients were dialyzed three times. the indication for repeat hd was persistent isolated metabolic acidosis (n=27, 17.5%) or metabolic acidosis with visual disturbances (n=10, 6.5%). the odds of being re-dialyzed more than once was 8.2 times more in the outbreak group (95% ci 1.6-41.1; p=0.001; table 4). despite this, hospital stay was also similar between the two groups. final outcomes were also similar, with 91% of patients recovering completely with no sequelae, while almost 4% recovered with some neurologic or ophthalmologic complication. death rates were similar between the groups (table 3), and the seven deaths were related to the severity of intoxication and organ injury on presentation. logistic regression analysis indicated that presenting during an outbreak, visual disturbance, and pulse rate were independent factors predicting the use of additional hd in methanol poisoned patients. also, a higher plasma creatinine concentration and lower ldh concentration were independently associated with presenting during an outbreak (table 4). an analysis of the alcohol sample available in the black market during the outbreak showed a 7-percent pure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hadipourzadeh et al. 4 methanol content of the beverage with no ethanol. 4. discussion in methanol poisoning, delayed initiation or insufficient hd can contribute to complications due to this condition, including death or severe and permanent neurological injury (11). therefore, it is advantageous if the number of required hd treatments for an individual can be predicted on admission to guide the allocation of resources and planning of treatments, especially in outbreaks when the resources are limited (8). according to our data, the presence of visual deficits on admission and presenting during an outbreak are independent predictors of requiring more hemodialysis treatments. a key laboratory indication for repeated hd is persistent metabolic acidosis, which was largely observed in patients presenting during an outbreak. this is interesting given that there were few statistically or clinically significant differences in admission characteristics and the time to present to hospital (although there was a non-significant trend of delayed presentation in the outbreak group). we could not confirm the exact cause of prolonged acidosis in outbreak cases, but we offer some hypotheses on the basis of these data. one possibility is that the higher initial methanol concentration, due to intake of beverages with a high methanol content, coupled with subtherapeutic adh blocking therapy in the context of an outbreak is associated with intermittent and prolonged metabolism of methanol to formic acid. this is a recognized risk of ethanol therapy, particularly given that blood ethanol concentrations cannot be routinely measured in our unit due to resource limitations. the risk of subtherapeutic adh inhibition is largely removed when fomepizole is used, but unfortunately, it is too expensive for routine use in our country. it was interesting to note that patients needing more sessions of hemodialysis presented with significantly lower ldh concentrations, because ldh has a role in clearing endogenous acids during energy metabolism. in the case of alcohol metabolism, the nadh2/nad ratio increases in both cytoplasm and mitochondria (12). higher nadh2 synthesis leads to a significant reduction of pyruvate by lactate dehydrogenase. although ldh can both reduce pyruvate and oxidize lactate, the preferred pathway is the transformation of pyruvate to lactate (13). this means that all pyruvate is reduced to lactate. moreover, inhibition of the respiratory chain by formic acid, the most toxic metabolite of methanol, leads to a rise in the nadh2/nad ratio (14). thus, in the later stages of acute methanol poisoning, the lactate concentration may increase, which contributes to a persistent metabolic acidosis in patients with lower ldh (15). regardless of the specific cellular processes involved, the significant correlation of ldh with other prognostic factors in methanol poisoning, including creatinine, serum bicarbonate, and serum blood sugar (16), prompts more research into the use of ldh for prognostication in methanol poisoning at the time of admission. it was interesting to note that patients who needed more sessions of hemodialysis during their hospitalization presented with statistically significant higher diastolic blood pressure and respiratory rate but a significantly lower core temperature. lower core temperatures have previously been shown to predict poor prognosis in methanol poisoning (17). on the other hand, higher diastolic blood pressure and higher respiratory rates in patients in the outbreak group may show elevated left ventricular end diastolic pressure (18) and higher production of acid in these patients due to more severe toxicity affecting the heart and metabolic adjustment of the body, respectively. however, we did not demonstrate that the severity of poisoning was higher in these patients and, therefore, the theory of more severe acidosis causing higher respiratory rate is not confirmed here. interestingly, the hospitalization period did not differ significantly between the two groups although the outbreak group patients had undergone hd at least once more than the other group. the risk of complications and death were also the same between the groups, which is an encouraging finding showing that our system is managing these patients properly despite all limitations in the equipment and resources, particularly during outbreaks. 5. limitations contrary to all the care taken to accurately record data in routine clinical practice, some data were not available in this retrospective study. although there were some differences in trends (for example, time to present) these non-statistically significant differences between the groups may have been due to underpowering of the cohort, so future studies would be useful to validate these observations and hypotheses. 6. conclusion during the methanol outbreaks, due to the contaminated alcoholic beverages available in the black market, poisoning can manifest with more persistent acidosis, which requires more hemodialysis sessions. close monitoring of the patients and repeated hemodialysis until acidosis is completely resolved is advocated. future prospective studies are warranted to further explore these clinical observations and to understand the reason for the persistent acidosis and treatment strategies that can prevent this; thus, preserving resources for methanol-poisoned patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e46 7. list of abbreviations adh= alcohol dehydrogenase gcs= glasgow coma scale hd= hemodialysis icd= international classification of disease ldh= lactate dehydrogenase vbg= venous blood gas nad= nicotinamide adenine dinucleotide spss= statistical package for social sciences 8. declarations 8.1. acknowledgments we wish to thank mrs. somaye sohrabi for data entry. this study is was based on fellowship thesis worked by dr. mehdi hadipourzadeh and supported by social determinants research center, shahid beheshti university of medical sciences. 8.2. funding and support this study was supported by a grant provided by shahid beheshti university of medical sciences (project id: 5050). 8.3. author contribution nz and hhm conceived and designed the study. mh and hf acquired the data. hhm, se and pz checked the data separately and performed the analysis. nz and dr drafted the manuscript. the final version of the manuscript was reviewed and approved by all authors. 8.4. availability of supporting data all collected and analyzed data can be made available by the corresponding author upon request. 8.5. conflict of interest none. references 1. hassanian-moghaddam h, zamani n. a brief review on toxic alcohols: management strategies. iranian journal of kidney diseases. 2016;10(6):344. 2. hassanian-moghaddam h, zamani n, roberts dm, brent j, mcmartin k, aaron c, et al. consensus statements on the approach to patients in a methanol poisoning outbreak. clinical toxicology. 2019;57(12):1129-36. 3. hassanian-moghaddam h, pajoumand a, dadgar s, shadnia s. prognostic factors in methanol poisoning. human & experimental toxicology. 2007;26(7):583-6. 4. paasma r, hovda ke, hassanian-moghaddam h, brahmi n, afshari r, sandvik l, et al. risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes–a multicenter study. clinical toxicology. 2012;50(9):823-31. 5. sefidbakht s, rasekhi a, kamali k, haghighi ab, salooti a, meshksar a, et al. methanol poisoning: acute mr and ct findings in nine patients. neuroradiology. 2007;49(5):427-35. 6. hassanian-moghaddam h, zamani n, kolahi a-a, mcdonald r, hovda ke. double trouble: methanol outbreak in the wake of the covid-19 pandemic in iran–a crosssectional assessment. critical care. 2020;24(1):1-3. 7. hassanian-moghaddam h, nikfarjam a, mirafzal a, saberinia a, nasehi aa, masoumi asl h, et al. methanol mass poisoning in iran: role of case finding in outbreak management. journal of public health. 2015;37(2):354-9. 8. pajoumand a, zamani n, hassanian-moghaddam h, shadnia s. can duration of hemodialysis be estimated based on the on-arrival laboratory tests and clinical manifestations in methanol-poisoned patients? international urology and nephrology. 2017;49(6):1057-62. 9. zakharov s, pelclova d, navratil t, belacek j, komarc m, eddleston m, et al. fomepizole versus ethanol in the treatment of acute methanol poisoning: comparison of clinical effectiveness in a mass poisoning outbreak. clinical toxicology. 2015;53(8):797-806. 10. kute vb, godara sm, shah pr, gumber mr, goplani kr, vanikar av, et al. hemodialysis for methyl alcohol poisoning: a single-center experience. saudi journal of kidney diseases and transplantation. 2012;23(1):37. 11. roberts dm, yates c, megarbane b, winchester jf, maclaren r, gosselin s, et al. recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. critical care medicine. 2015;43(2):461-72. 12. baud fj, borron sw, bavoux e, astier a, hoffman jr. relation between plasma lactate and blood cyanide concentrations in acute cyanide poisoning. bmj. 1996;312(7022):26-7. 13. dudka j, burdan f, szumilo j, tokarska e, korobowicz a, klepacz r, et al. effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity—an in vitro study. journal of applied toxicology: an international journal. 2005;25(6):549-53. 14. jacobsen d, mcmartin ke. methanol and ethylene glycol poisonings. medical toxicology. 1986;1(5):309-34. 15. shahangian s, ash k. formic and lactic acidosis in a fatal case of methanol intoxication. clinical chemistry. 1986;32(2):395-7. 16. sanaei-zadeh h, esfeh sk, zamani n, jamshidi f, shadnia s. hyperglycemia is a strong prognostic factor of lethality in methanol poisoning. journal of medical toxicology. 2011;7(3):189-94. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hadipourzadeh et al. 6 17. lee c-y, chang ek, lin j-l, weng c-h, lee s-y, juan kc, et al. risk factors for mortality in asian taiwanese patients with methanol poisoning. therapeutics and clinical risk management. 2014;10:61. 18. cavalli a, volpi a, maggioni ap, tusa m, de pieri g. severe reversible cardiac failure associated with methanol intoxication. postgraduate medical journal. 1987;63(744):8678. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e46 figure 1: timeline of patient referrals due to methanol poisoning in outbreak (red) or episodic (blue) events during one year in loghmanhakim hospital. figure 2: patient inclusion chart. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hadipourzadeh et al. 8 table 1: comparing the presenting characteristics and outcomes between epidemic and episodic methanol poisoning referrals variables epidemic (n=88) episodic (n =66) p gender male 76 (86.4) 57 (86.4) 0.999 age (years) median (iqr) 30 (24-37) 28 (25-37) 0.958 presenting vital signs glasgow coma scale 15 (14-15) 15 (15-15) 0.518 systolic bp (mmhg) 110 (110-120) 110 (110-120) 0.659 diastolic bp (mmhg) 70 (70-80) 70 (70-70) 0.005 pulse rate (/minutes) 90 (80-100) 92 (84-100) 0.625 respiratory rate (/minutes) 17 (14-18) 16 (14-18) 0.027 temperature (c) 37 (36.8-37) 37 (36.9-37.4) 0.004 presenting chief complaint vomiting 41 (46.6) 39 (59.1) 0.126 nausea 40 (45.5) 34 (51.5) 0.458 abdominal pain 10(11.4) 4 (6.1) 0.259 blurred vision 74 (84.1) 52 (78.8) 0.400 floaters and flashes 3 (3.4) 2 (3.0) 0.896 visual loss 6 (6.8) 6 (9.1) 0.604 photophobia 3 (3.4) 3 (4.5) 0.719 seizure 3 (3.4) 1 (1.5) 0.466 headache 22 (25) 14 (21.2) 0.584 co-ingestion yes 75 (7.6) 2 (2.3) 0.139 consumption characteristic amount (cc) 500 (300-1000) 500 (300-1000) 0.915 lag to refer to ed (hours) 35 (24-48) 24 (24-48) 0.802 dialysis session 1 57 (64.8) 60 (90.9) 0.001† ≥ 2 31 (35.2) 6 (9.1) hospitalization duration (days) median (iqr) 1 (1-3) 1 (1-2.5) 0.171 need for intubation yes 6 (6.8) 2 (3.0) 0.295 final outcome complete recovery 79 (90.8) 59 (92.2) recovery with complication 3 (3.4) 3 (4.7) 0.706 death 5 (5.8) 2 (3.1) data are presented as frequency (%) or median (inter quartile range (iqr)). bp: blood pressure, ed: emergency department. †odds ratio 5.4 (95% ci 2.1-14.0). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e46 table 2: comparing the laboratory findings of studied cases between epidemic and episodic methanol poisoning referrals parameters epidemic (n = 88) episodic (n = 66) p ph on presentation 7.20 (7.12-7.26) 7.21 (7.15-7.28) 0.441 pco2 on presentation (mmhg) 28.8 (22.8-34.9) 26.6(21.6-35.7) 0.631 hco3 on presentation (mmhg) 12 (9.3-15.7) 12 (9.5-15.8) 0.797 ph before first hd 7.20 (7.12-7.26) 7.21 (7.15-7.26) 0.737 pco2 before first hd (mmhg) 28.8 (22.8-34.2) 26.1 (21.6-35.5) 0.414 hco3 before first hd (mmhg) 12.0 (9.3-15.6) 12.0 (9.4-15.2) 0.762 blood sugar (mg/dl) (n=151) 112 (94-138) 109. (93-143) 0.820 bun (mg/dl) (n=151) 27 (22-37) 31 (24-40) 0.043 creatinine (mg/dl) (n=151) 1.3 (1.1-1.4) 1.2 (1-1.4) 0.032 natrium (meq/l) (n=151) 138 (136-141) 139 (136-141) 0.320 potassium (meq/l) (n=152) 4.2 (4-4.4) 4.3 (4-4.6) 0.503 methanol level (mg/dl)* (n=130) 11.2 (0-30.6) 0 (0-13.8) 0.011 creatine phosphokinase (iu/l) (n=123) 131 (95-218) 107 (77-195) 0.306 lactate dehydrogenase (iu/l) (n=122) 400 (331-503) 488 (400-658) 0.001 ph before second hd (n=31) 7.31 (7.29-7.39) 7.26 (7.23-7.34) 0.293 pco2 before second hd (n=31) (mmhg) 26.5 (22.8-32.2) 27.8 (19-31.2) 0.544 hco3 before second hd (n=31) (mmhg) 16.4 (13.2-18) 14.0 (10.2-16.7) 0.177 ph before third hd (n=7) 7.41 (7.32-7.49) 7.06 (7.06-7.06) 0.134 pco2 before third hd (n=7) (mmhg) 26.3 (24.4-29.7) 77.9 (77.9-77.9) 0.134 hco3 before third hd (n=7) (mmhg) 16.9 (12-21.5) 22.1 (22.1-22.1) 0.134 data are presented as median (inter quartile range). hd: hemodialysis session. * due to long lag time between poisoning and presenting to the emergency department in some clinically confirmed cases, the serum level of methanol was undetectable. bun: blood urea nitrogen. table 3: comparing the outcomes of studied cases between epidemic and episodic methanol poisoning referrals variables epidemic (n=88) episodic (n =66) p dialysis session 1 57 (64.8) 60 (90.9) 0.001 ≥ 2 31 (35.2) 6 (9.1) hospitalization duration (days) median (iqr) 1 (1-3) 1 (1-2.5) 0.171 need for intubation yes 6 (6.8) 2 (3.0) 0.295 final outcome complete recovery 79 (90.8) 59 (92.2) recovery with complication 3 (3.4) 3 (4.7) 0.706 death 5 (5.8) 2 (3.1) data are presented as number (%). iqr: inter quartile range. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hadipourzadeh et al. 10 table 4: logistic regression analysis for independent predictive factors of repeated dialysis (dialysis sessions) and being in a methanol outbreak based on on-arrival variables variable beta se or (95% ci) r# p value dialysis sessions* (1 vs. ≥2) outbreak 2.10 0.82 8.16 (1.62-41.09) 0.477 <0.001 visual disturbance 1.71 0.81 5.52 (1.13, 26.96) being in a methanol outbreak (yes vs. no)† pulse rate 0.061 0.027 1.06 (1.0, 1.12) creatinine 2.07 1.03 7.92 (1.04, 60.21) 0.379 0.012 lactate dehydrogenase -0.005 0.002 0.996 (0.995, 0.998) *all variables with p values less than 0.2 were entered in the model including: creatinine, methanol level, systolic and diastolic blood pressure, temperature, pulse and respiratory rate, on-arrival ph, pco2 , hco3 , glasgow coma scale, lag period between consumption and presentation, outbreak (yes vs. no), visual disturbance (yes vs. no). † all variables with p values less than 0.2 were entered in the model including: creatinine, blood urea nitrogen, lactate dehydrogenase, methanol level, diastolic blood pressure, temperature, respiratory rate, and vomiting (yes vs. no). #: nagelkerke r square. or: odds ratio, se: standard error. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion list of abbreviations declarations references archives of academic emergency medicine. 2021; 9(1): e15 https://doi.org/10.22037/aaem.v9i1.1060 or i g i n a l re s e a rc h determining the need for computed tomography scan following blunt chest trauma through machine learning approaches mohsen shahverdi kondori1, hamed malek1∗ 1. faculty of computer science and engineering, shahid beheshti university, tehran, iran. received: december 2020; accepted: december 2020; published online: 24 january 2021 abstract: introduction: the use of computed tomography (ct) scan is essential for making diagnoses for trauma patients in emergency medicine. numerous studies have been conducted on guiding medical examinations in light of advances in machine learning, leading to more accurate and rapid diagnoses. the present study aims to propose a machine learning-based method to help emergency physicians prevent performance of unnecessary ct scans for chest trauma patients. methods: a dataset of 1000 samples collected in nearly two years was used. classification methods used for modeling included the support vector machine (svm), logistic regression, naïve bayes, decision tree, multilayer perceptron (four hidden layers), random forest, and k nearest neighbor (knn). the present work employs the decision tree approach (the most interpretable machine learning approach) as the final method. results: the accuracy of 7 machine learning algorithms was investigated. the decision tree algorithm was of higher accuracy than other algorithms. the optimal tree depth of 7 was chosen using the training data. the accuracy, sensitivity and specificity of the final model was calculated to be 99.91% (95%ci: 99.10% – 100%), 100% (95%ci: 99.89% – 100%), and 99.33% (95%ci: 99.10% – 99.56%), respectively. conclusion: considering its high sensitivity, the proposed model seems to be sufficiently reliable for determining the need for performing a ct scan. keywords: radiography; tomography, x-ray computed; clinical decision rules; decision trees; machine learning cite this article as: shahverdi kondori m, malek h. determining the need for computed tomography scan following blunt chest trauma through machine learning approaches. arch acad emerg med. 2021; 9(1): e15. 1. introduction a number of studies have been published, which preferred to use chest computed tomography (ct) scan rather than chest x ray (cxr) in evaluation of traumatic thoracic injuries (1, 2). it may be impossible to completely evaluate patients and provide rapid medical services when they go to emergency departments due to limitations in time, human resources, and equipment, particularly during natural disasters with a high number of visits. in such situations, the use of clinical decision rules may be very effective in accelerating the decision-making process and can determine the priority of caring for patients and accelerate the discharge of those who do not need further care (3). evidence-based in∗corresponding author: hamed malek; shahid beheshti university, shahid shahriari square, daneshjou boulevard, shahid chamran highway, tehran, iran. email: h_malek@sbu.ac.ir, phone/fax: +98 (21) 29904106, orcid: https://orcid.org/0000-0003-4314-6539 dications for ct scan in blunt thoracic trauma have not been extensively reviewed. in an attempt in this regard, safari et al. showed that cases with normal cxr may skip chest ct scan (4). accordingly, the present study proposes a model to predict whether a chest ct scan is necessary, using machine learning and artificial intelligence tools and a dataset collected from patients who underwent chest ct scans. 2. methods 2.1. dataset the dataset consisted of the data of 1000 trauma patients who referred to shohadaye tajrish and imam hossein hospitals, which are two large trauma research centers in tehran, from january 2017 to july 2018. all of the patients underwent initial examinations and ct scans. the data were collected from adult patients at ages above 18 years and included patients’ personal information (i.e., age and gender), incident details, trauma mechanism (either high or low energy), vithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shahverdi kondori et al. 2 tal signs (i.e., heart rate, respiratory rate, blood pressure, and oxygen saturation), level of consciousness, clinical examination and history taking findings (including dyspnea, respiratory sounds, reduced cardiac sounds, chest wall deformity, distracting pain, generalized tenderness, chest wall tenderness, chest wall abrasion, crepitation, jugular venous pressure ( jvp), and chest wall pain), ct scan findings, x-ray images, and sonography results. table 1 provides the data. 2.2. preprocessing in the first preprocessing stage, a number of dataset fields were found to be irrelevant and were excluded, including gender and transportation to the hospital, as shown in column 3 of table 1. it should be noted that the exclusion of irrelevant data increases the model’s accuracy. glasgow coma scale (gcs) field, which indicates the level of consciousness was also excluded as it divided patients into conscious and unconscious patients. the items excluded in this stage are shown in column 3 of table 1. in the second stage, preprocessing methods used in machine learning algorithms were applied to the data. then, irrelevant or non-effective items obtained in the second preprocessing stage based on model training results, including o2 saturation and hemoglobin level, were excluded from the dataset. then, x-ray and sonography data were excluded, since they had a high correlation with the target value, as shown in column 4 of table 1. this is further explained below. before performing the learning process with the remaining items, some categorical data, including chest ct scan findings and type of high energy trauma, were quantized using the one-hot vector method (5), as presented in column 2 of table 2. the one-hot vector transforms categorical data into binary values, allowing for building a better model through machine learning methods. in the third stage, the remaining data were reviewed by an expert, excluding the medically irrelevant fields and ct scan-requiring fields from the dataset, as shown in column 5 of table 1. then, a number of items that were deemed to have the same implications by the expert were integrated, as provided in column 7 of table 1. thus, only column 7 remained for the learning process. then, machine learning algorithms were trained using the remaining data. in dealing with trauma patients, some signs necessitate ct scans, regardless of other conditions. for example, a chest wall deformity requires the medical team to perform a ct scan. the gcs level is another sign that leads physicians to prescribe ct scans – if a patient is not conscious, a ct scan must be performed. thus, these items were also excluded from the dataset for model training. 2.3. machine learning algorithms machine learning is one of the most commonly employed artificial intelligence classes. it adjusts and discovers practices and algorithms by which computers and systems can learn. classification account for a set of machine learning algorithms. the main objective of classification algorithms is to classify data into distinct groups that can detect new data. classification methods include the support vector machine (svm), logistic regression, naïve bayes (6), decision tree, multilayer perceptron (four hidden layers)(7), random forest, and k nearest neighbor (knn) (8). such methods have advantages and disadvantages, and the best method to address the problems should be chosen based on the specific problem and its requirements. the decision tree approach was chosen in the present study as it provides more explanation for the results, which was importance in this study. 2.4. decision tree the decision tree approach is a decision support tool that uses trees for modeling. decision trees are typically employed in different operations, such as decision analysis, to find the best strategy to classify data. a condition is investigated in each node of a decision tree. the algorithm follows one of the two branches of a node based on whether the condition is met. this continues until a leaf is reached. finally, decisions are made based on the number of each class of samples in a given leaf. particularly, after investigating the entire conditions on the input data in the proposed problem, the algorithm will produce a positive outcome if the number of training samples that suggest performing a ct scan is higher than those that do not suggest performing a ct scan; otherwise, it will produce a negative outcome. each move from a node to another adds a unit to the tree depth. the tree depth is a parameter that should be either identified during the learning process, or chosen based on the optimal depth determined using optimal depth identification methods. 2.5. data segmentation in a machine learning algorithm, data are segmented into training, validation, and test data. it should be noted that classification should be performed randomly. accordingly, 60%, 20%, and 20% of the data were selected as training, validation, and test data, involving 600, 200, and 200 samples, respectively. the svm, logistic regression, naïve bayes, decision tree, multilayer perceptron (four hidden layers), random forest, and knn algorithms were applied to the data. then, the models were evaluated using the validation data. the validation results showed a higher accuracy for the decision tree algorithm. thus, the decision tree model was adopted. then, 70% of the data were used to find the optimal depth, while the remaining 30% were employed as the test data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e15 2.6. evaluation criteria an evaluation criterion should be used to compare machine learning algorithms and detect their efficiency. the present study employed accuracy as the evaluation criterion. then, sensitivity was used to determine the optimal tree. in general, sensitivity is of great importance in analyzing medical data, since it represents how accurate a model is in diagnosis. 3. results the above-mentioned machine learning algorithms were investigated by the criterion of accuracy. table 2 provides the training and validation accuracy of different machine learning algorithms. as can be seen, the decision tree algorithm had a higher accuracy compared to other algorithms. it should be noted that the results were obtained after excluding the x-ray and sonography data. in fact, the idea is to propose a model that can be employed even without x-ray and sonography equipment. table 3 shows the accuracy of the proposed decision tree in different depths of the model. as can be seen, a decision tree depth of 7 was chosen. after choosing the decision tree, the tree’s depth should be measured as a parameter. the optimal tree depth was selected using the training data based on table 4. finally, a rule (algorithm) was obtained to be proposed to emergency physicians based on the obtained model, application of x-ray and sonography data, and incorporation of the data that were excluded from the procedure by the expert. figure 1 presents the final model. 4. discussion in this work an interpretable machine learning model was introduced to help emergency physicians to prevent performance of unnecessary ct scans for chest trauma patients. due to the simplicity of the model, it is a very good choice for patient classification in order to prevent the crowding problems in critical conditions such as natural disasters like earthquakes, floods, and volcanoes. this model has good accuracy and high generalizability due to being usable in the presence or absence of sonography and x-ray results. the model, which is the final and pruned model of the decision tree, can be easily implemented in the rule diagram. shapley value (9) is an analytical method in game theory, which is used in machine learning in order to increase the interpretability of models (10). the shapley value explores the hypothesis space by considering the presence or absence of each parameter. finally, the contribution of each parameter to the accuracy of the model is obtained as a result. in order to evaluate the sensitivity of the model to each parameter, we analyzed each of the parameters used in the model to find out the impact of each parameter on model output magnitude. in figure 4, x-axis represents the effect of each parameter on the accuracy of the model and y-axis represents the order of importance of the model parameters. as can be seen, gcs categories, age, and loss of pulmonary sound have the most impact on the results of the model in detecting the correct classes. it was demonstrated that the proposed model’s sensitivity is high in identifying cases for which ct scan should be performed, and its specificity is acceptable. the model is proved to be effective with high reliability in reducing the number of patients that need ct scans. 5. conclusion trauma poses a challenge in emergency departments regarding providing early care for patients. proper hospital equipment is required to perform ct scans on trauma patients and its cost is high. the present study proposed a decision treebased model to determine whether a ct scan is necessary early on. considering its high sensitivity, the proposed model seems to be sufficiently reliable in determining the need for performing a ct scan. 6. declarations 6.1. acknowledgment not applicable. 6.2. author contributions all authors passed the criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding none. 6.4. conflict of interest the authors have no conflict of interest to declare references 1. sangster gp, gonzález-beicos a, carbo ai, heldmann mg, ibrahim h, carrascosa p, et al. blunt traumatic injuries of the lung parenchyma, pleura, thoracic wall, and intrathoracic airways: multidetector computer tomography imaging findings. emergency radiology. 2007;14(5):297-310. 2. traub m, stevenson m, mcevoy s, briggs g, lo sk, leibman s, et al. the use of chest computed tomography verthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shahverdi kondori et al. 4 sus chest x-ray in patients with major blunt trauma. injury. 2007;38(1):43-7. 3. shafaf n, malek h. applications of machine learning approaches in emergency medicine; a review article. archives of academic emergency medicine. 2019;7(1). 4. safari s, farbod m, hatamabadi h, yousefifard m, mokhtari n. clinical predictors of abnormal chest ct scan findings following blunt chest trauma: a cross-sectional study. chinese journal of traumatology. 2020;23(1):51-5. 5. digital design and computer architecture 2nd edition. 6. khanna d, sharma a, editors. kernel-based naive bayes classifier for medical predictions2018 2018. singapore: springer. 7. hastie t, tibshirani r, friedman j. the elements of statistical learning: data mining, inference, and prediction, second edition. 2nd edition ed. new york, ny: springer; 2016 2016/01/01/. 767 p. 8. jiang l, cai z, wang d, jiang s, editors. survey of improving k-nearest-neighbor for classification. fourth international conference on fuzzy systems and knowledge discovery (fskd 2007); 2007 2007/08//. 9. molnar c. interpretable machine learning: lulu.com; 2020 2020/02/28/. 320 p. 10. maleki s, tran-thanh l, hines g, rahwan t, rogers a. bounding the estimation error of sampling-based shapley value approximation. arxiv:13064265 [cs]. 2014. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e15 table 1: the patient data of the dataset field name data type deleted in step one deleted in step two deleted by expert comment change@ merge used# chest x-ray binary × p chest x-ray binary × age numerical × gender binary × fast sonography binary × p drug history binary × chest wall deformity binary × p transfer to hospital categorical × chest wall tenderness binary p systolic blood pressure numerical × • distracting pain binary p diastolic bp numerical × • loss of cardiac sound binary p glasgow coma scale (gcs) numerical × chest wall abrasion binary p respiratory rate numerical × • generalized tenderness binary o2 saturation numerical × chest wall pain binary p high energy trauma binary × medical history binary p high energy trauma categorical × × heart rate binary × • dyspnea binary p chest ct scan binary p tachypnea binary p hemoglobin level numerical × pulmonary sound* binary p chest ct scan finding categorical × crepitation binary p trauma mechanism categorical × jvp enlargement binary p age categories binary p unstable hemodynamics binary × • p gcs categories binary × p @: change to one hot; #: used for final model, *: loss of pulmonary sound; bp: blood pressure; jvp: jugular vein pressure; gcs: glasgow coma scale; ct: computed tomography. table 2: the accuracy of different models in training and validation phases model list accuracy (95% ci) training validation support vector machine 84.6 (79.87 89.33) 80.5 (74.62 – 86.38) k nearest neighbor (k = 5) 81.33 (76.38 86.28) 76.5 (71.23 81.77) logistic regression 82 (74.33 – 89.66) 77 (69.22 – 84.78) random forest 85.33 (80.01 90.65) 80.5 (74.53 86.47) naive bayes 80.5 (73.44 87.56) 74 (66.18 81.82) multilayer perceptron (3 hidden layers) 85 (81.67 – 88.33) 82 (77.97 – 86.03) decision tree (depth = 7) 87 (84.12 89.88) 85 (81.58 – 88.42) data are presented with 95 % confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shahverdi kondori et al. 6 table 3: different decision tree depths and accuracies obtained on the test, validation, and sensitivity data depth* accuracy (95% ci) test sensitivity training test 3 81.85 (78.75 – 84.95) 83.33 (79.53 – 87.13) 95.45 (92.55 – 98.35) 4 83.14 (80.08 – 86.2) 83.66 (79.8 – 87.52) 97.47 (94.66 – 100) 5 84.28 (81.27 – 87.29) 84 (80.28 – 87.72) 95.95 (93.43 – 98.47) 6 85.28 (82.41 – 88.15) 84.33 (80.66 – 88) 95.45 (93.44 – 97.46) 7 86.57 (83.79 – 89.35) 85 (81.51 – 88.49) 97.47 (95.59 – 99.35) 8 87.28 (84.56 – 90) 85.33 (81.73 – 88.93) 97.47 (95.55 – 99.39) 9 88.14 (85.52 – 90.76) 83.66 (79.94 – 87.38) 93.93 (91.96 – 95.9) 10 88.85 (86.25 – 91.45) 84.66 (80.73 – 88.59) 94.94 (92.88 – 97) *: model depth. data are presented with 95% confidence interval. table 4: the decision tree results with and without considering the chest x-ray and sonography findings model accuracy (95% ci) test training test sensitivity specificity with 99.95 (99.28 – 100) 99.91 (99.1 – 100) 100 (99.81 – 100) 99.33 (99.1 – 99.56) without 85.5 (93.32 – 87.68) 84.66 (81.9 – 87.42) 98.96 (98.05 – 99.87) 77.83 (72.49 – 83.17) data are presented with 95% confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e15 figure 1: the final model obtained by re-including the excluded data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shahverdi kondori et al. 8 figure 2: the contribution of parameters to model accuracy. jvp: jugular vein pressure; gcs: glasgow coma scale. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e64 or i g i n a l re s e a rc h physiologic scoring systems versus glasgow coma scale in predicting in-hospital mortality of trauma patients; a diagnostic accuracy study farhad heydari1, reza azizkhani1∗, omid ahmadi1, saeed majidinejad1, mohammad nasr-esfahani1, ahmad ahmadi1 1. department of emergency medicine, faculty of medicine, isfahan university of medical sciences, isfahan, iran. received: july 2021; accepted: august 2021; published online: 23 september 2021 abstract: introduction: in recent years, several scoring systems have been developed to assess the severity of trauma and predict the outcome of trauma patients. this study aimed to compare rapid emergency medicine score (rems), modified early warning score (mews), injury severity score (iss), and glasgow coma scale (gcs) in predicting the in-hospital mortality of trauma patients. methods: this diagnostic accuracy study was done on adult patients admitted to the emergency department (ed) between june 21, 2019, and september 21, 2020, following multiple trauma. patients were followed as long as they were hospitalized. the rems, mews, gcs, and iss were calculated after data gathering and comprehensive assessment of injuries. receiver operating characteristics (roc) analysis was performed to examine the prognostic performance of the four different tools. results: of the 754 patients, 32 patients (4.2%) died and 722 (95.8%) survived after 24 hours of admission. the mean age of the patients was 38.54 ± 18.58 years (78.9% male). the area under the roc curves (auc) of rems, mews, iss, and gcs score for predicting in-hospital mortality were 0.942 (95% ci [0.923-0.958]), 0.886 (95% ci [0.861-0.908]), 0.866 (95% ci [0.839-0.889]), and 0.851 (95% ci [0.823-0.876]), respectively. the auc of rems was significantly higher than gcs (p=0.035). the sensitivities of gcs ≤ 11, iss ≥ 13, rems ≥ 4, and mews ≥ 3 scores for in-hospital mortality were 0.56, 0.97, 0.81, and 0.94, respectively. also, the specificities of gcs, iss, rems, and mews scores for in-hospital mortality were 0.93, 0.82, 0.81, and 0.85, respectively. conclusion: it seems that rems is more accurate than gcs, iss, and mews in predicting in-hospital mortality ≥ 24 hours of multiple trauma patients. keywords: multiple trauma; injury severity score; scoring system/ clinical decision rules; emergency service, hospital; patient outcome assessment; prognosis cite this article as: heydari f, azizkhani r, ahmadi o, majidinejad s, nasr-esfahani m, ahmadi a. physiologic scoring systems versus glasgow coma scale in predicting in-hospital mortality of trauma patients; a diagnostic accuracy study. arch acad emerg med. 2021; 9(1): e64. https://doi.org/10.22037/aaem.v9i1.1376. 1. introduction trauma and unintentional injuries kill more than 175,000 americans each year and are the leading cause of death in people under 45 years of age (1). also, trauma causes severe complications, disability, and financial and social costs (2, 3). early diagnosis and appropriate triage and immediate treatment decrease in-hospital mortality and are costeffective (4). in recent years, several scoring systems have ∗corresponding author: reza azizkhani; department of emergency medicine, alzahra hospital, sofeh ave, keshvari blvd., isfahan, iran. email: r_azizkhani@med.mui.ac.ir, tel: +989131367643, orcid: http://orcid.org/0000-0002-5823-4374. been implemented to assess the severity of the injuries and determine which patients need intensive observation, treatment, and appropriate allocation of healthcare resources (3, 5, 6). national early warning score (news), rapid acute physiology score (raps), rapid emergency medicine score (rems), worthing physiological scoring system (wpss), and modified early warning score (mews) are some of the most commonly used scoring systems. glasgow coma scale (gcs) is used to assess a person’s level of consciousness and head injury severity. this scale is used by emergency medical services, nurses, and physicians, and is applied for all acute medical and trauma patients (7). injury severity score (iss) is an established medical score to assess trauma severity. it is an anatomy-based scoring systhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 2 tem to predict the outcome of victims with multiple injuries (3). rems, which is a powerful predictor of in-hospital mortality among medical (non-trauma) patients admitted to the hospital was developed in 2004 (8). rems consists of six key parameters: patient’s age, mean arterial pressure (map), heart rate, respiratory rate, spo2, and glasgow coma scale. also, mews can be used to identify patients who are at risk of clinical deterioration and who may require a higher level of care (9). mews comprises five physiological parameters: systolic blood pressure (sbp), heart rate, respiratory rate, temperature, and avpu score. this study aimed to compare the diagnostic accuracy of 3 physiologic scoring systems including rapid emergency medicine score (rems), modified early warning score (mews), and injury severity score (iss), as well as glasgow coma scale (gcs) in predicting in-hospital mortality of trauma patients. 2. methods 2.1. study design and setting this was a prospective diagnostic accuracy study of adult multiple trauma patients admitted to al-zahra and kashani hospitals, two university educational hospitals, affiliated with isfahan university of medical sciences, isfahan, iran. this study was approved by the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1398.340) and an informed consent form was obtained from patients. 2.2. participants all multiple trauma patients (two or more body region injuries), who were aged 18 years and older and were admitted to the emergency department (ed) between june 21, 2019, and september 21, 2020, were included in the study. patients were enrolled regardless of trauma severity. exclusion criteria were patients with missing data necessary to calculate scores, discharge or death in less than 24 hours from admission, patients transferred from other hospitals, burn or drowning-related injuries, pregnancy, and discharge against medical advice. iss was calculated after complete evaluation of the patient and receiving the results such as imaging results, intervention findings, and operative records, so comprehensive assessment of injuries could take substantial time, therefore hospitalization for at least 24 hours was considered to calculate iss in all patients. 2.3. data gathering after multiple trauma patients arrived at the ed, the triage nurse evaluated them on the basis of emergency severity index (esi) version 4, and then, the patients were transferred to the emergency room according to the level of the triage. then all participants were examined by emergency medicine residents upon their arrival and they took over the patient’s treatment and follow-up. sampling was performed using the convenience method. age, sex, systolic blood pressure (sbp), diastolic blood pressure (dbp), respiratory rate (rr), heart rate (hr), gcs, avpu score, temperature, oxygen saturation, length of hospital stay, mechanism of injury, triage level based on esi and inhospital mortality, were collected for each patient. patients were followed during their hospital stay to evaluate their final outcome. the in-hospital mortality was defined as death during the present hospital stay. rems consists of 6 parameters, 5 physiological and 1 age (8). the highest score is 26 with higher values being indicative of a worse prognosis. mews consists of 5 physiological parameters (9). the range of mews total score is from 0 to a maximum of 14. iss is an anatomical scoring system for patients with multiple injuries. iss is based on abbreviated injury scale (ais), which divides the body into six regions. iss is calculated as the sum of the squares of the highest ais code in each of the three most severely injured body regions and has a range from 0 to 75 (3). rems and mews scores were calculated according to the physiological criteria that were evaluated on admission to ed. iss scores were calculated after data gathering and comprehensive assessment of injuries. 2.4. statistical analysis considering the 5.2% prevalence of in-hospital mortality in trauma patients (10) and area under the curve of gcs in predicting in-hospital mortality being 0.88 (11) and marginal error of 0.05, the minimum required sample size was calculated to be 337 patients. spss version 25.0 (ibm, armonk, ny) was used to analyze the variables. categorical variables were described as frequency and percentage and continuous variables were described as mean and standard deviation (sd) or median and interquartile ranges (iqr). chi-square or fisher’s exact test were used for the comparisons between categorical variables and independent samples t-test or mann-whitney u test were used for the comparisons between continuous variables. the predictive values of rems, mews, iss, and gcs in predicting in-hospital mortality were compared using the area under the receiver operating characteristic curve (auc) with a 95% confidence interval (ci). sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values with 95% ci were reported for each score. pvalues less than 0.05 were considered statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e64 table 1: comparison of demographic and clinical characteristics of multiple trauma patients according to in-hospital mortality after ≥ 24 hours of admission characteristics total (n=754) survived (n=722) non-survived (n=32) p value age, (year) mean ± sd 38.54±18.58 38.13±18.09 47.75±28.31 0.1331 sex, n(%) female 159 (21.1) 155 (21.5) 4 (12.5) 0.2232 male 595 (78.9) 567 (78.5) 28 (87.5) mechanism, n (%) road injuries 529 (70.3) 507 (70.3) 22 (68.7) fall 124 (16.5) 114 (15.8) 10 (31.3) 0.1162 assault 95 (12.7) 95 (13.1) 0 (0.0) others 6 (0.5) 6 (0.8) 0 (0.0) triage level, n (%) 1 158 (21.0) 130 (18.0) 28 (87.5) 2 396 (52.5) 392 (54.3) 4 (12.5) <0.0012 3 200 (26.5) 200 (27.7) 0 (0.0) glasgow coma scale, n (%) 3-8 40 (5.3) 20 (2.8%) 20 (62.5%) 9-12 30 (4.0) 26 (3.6%) 4 (12.5%) <0.0012 13-14 24 (3.2) 24 (3.3%) 0 (0.0%) 15 660 (87.5) 652 (90.3%) 8 (25.0%) length of stay, (day) mean ± sd 6.25±5.78 6.31±5.84 5.14±5.11 0.6251 vital signs* hr, (bpm) 87.42±14.19 87.03±13.74 96.24±20.45 0.0141 sbp, (mmhg) 129.87±19.31 130.34±16.87 119.18±17.45 <0.0011 map, (mmhg) 90.23±13.13 90.85±32.70 76.15±11.48 <0.0011 rr, (bpm) 19.20±3.68 19.18±3.48 19.68±7.54 0.7851 temp, (°c) 36.97±0.31 36.99±0.31 36.88±0.16 0.5971 o2 sat, (%) 94.58±3.11 94.57±2.99 94.88±5.03 0.5841 injury severity (median (iqr))* iss 9 (5-14) 9 (5-14) 23 (15-29) <0.0013 gcs 15 (14-15) 15 (14-15) 11 (4-15) <0.0013 mews 1 (1-2) 1 (1-2) 4 (3-4.75) <0.0013 rems 0 (0-3) 0 (0-3) 8 (6-10.5) <0.0013 iqr: interquartile range, sd: standard deviation, hr: heart rate; sbp: systolic blood pressure; mean arterial pressure; rr: respiratory rate; temp: temperature; sat: saturation; iss: injury severity score; gcs: glasgow coma scale; mews: modified early warning score; rems: rapid emergency medicine score. 1 analyzed using via independent-samples t test. 2 analyzed using fisher’s exact test. 3 analyzed using mann-whitney u test. * these data were evaluated at the time of admission to emergency department. 3. results of the 754 patients included in this study, 32 patients (4.2%) died and 722 patients (95.8%) were discharged from hospital (figure 1). the mean age of the patients was 38.54 ± 18.58 (18 –94) years (78.9% male). road injuries were the main cause of trauma (70.3%) followed by falls (16.5%). 391 patients (51.9%) required surgery and 185 patients (24.5%) were admitted to the icu. the median gcs, iss, rems, and mews scores (iqr) were 15 (14-15), 9 (5-14), 0 (0-3) and 1 (1-2), respectively. according to the emergency severity index (esi) triage system, 21.0%, 52.5%, and 26.5% of the patients were categorized as levels i, ii, and iii, respectively. the mean duration of hospital stay was 6.28 ± 5.78 days. mean vital sign measures of the patients and other baseline characteristics have been reported in table 1. the area under the roc curves of rems, mews, iss, and gcs scores in predicting the in-hospital mortality of trauma patients were 0.942 (95% ci: 0.923-0.958), 0.886 (95% ci: 0.861-0.908), 0.866 (95% ci: 0.839-0.889) and 0.851 (95% ci: 0.823-0.876), respectively (figure 2). the optimal cut-off values for the mentioned scores were ≥4 for rems, ≥3 for mews score, ≥13 for iss, and ≤11 for gcs. the sensitivities of gcs, iss, rems, and mews scores in these cutoff points were 0.56, 0.97, 0.81, and 0.94, respectively. also, the specificities of gcs, iss, rems, and mews scores for in-hospital this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 4 table 2: screening performance characteristics of physiologic scoring systems (rems, mews, iss) and glasgow coma scale (gcs) in prediction of in-hospital mortality variables rems mews iss gcs cut-off ≥4 ≥3 ≥13 ≤ 11 sensitivity 96.87 (83.8 99.9) 93.75 (79.2 99.2) 81.25 (54.4-96.0) 56.25 (37.7 73.6) specificity 81.30 (78.3 84.1) 84.76 (81.9 87.3) 81.59 (77.1-85.5) 93.35 (91.3 95.1) ppv 16.2 (8.7-26.6) 21.3 (11.9-33.7) 16.7 (9.2-26.8) 37.0 (19.4-57.6) npv 98.6 (96.6-99.6) 99.0 (97.2-99.8) 99.0 (97.0-99.8) 98.2 (96.2-99.4) plr 5.18 (4.4 6.1) 6.15 (5.1 7.5) 4.41 (3.2-6.1) 8.46 (5.6 12.7) nlr 0.04 (0.01 0.3) 0.07 (0.02 0.3) 0.23 (0.08-0.6) 0.47 (0.3 0.7) auc 0.942 (0.923-0.958) 0.886 (0.861-0.908) 0.866 (0.839-0.889) 0.851 (0.823-0.876) data are presented with 95% confidence interval. abbreviations: rems: rapid emergency medicine score; mews: modified early warning score; iss: injury severity score; gcs: glasgow coma scale; ppv: positive predictive value; npv: negative predictive value; auc; area under curve; plr: positive likelihood ratio, nlr: negative likelihood ratio. table 3: comparison of the area under the receiver operating characteristic (roc) curve of studied scores scores rems mews gcs iss rems 0.107 0.035 0.010 mews 0.456 0.528 gcs 0.723 iss iss: injury severity score; gcs: glasgow coma scale; mews: modified early warning score; rems: rapid emergency medicine score. figure 1: consort flow diagram. mortality were 0.93, 0.82, 0.81, and 0.85, respectively (table 2). gcs was similar to mews (p=0.456) and iss (p=0.723) in predicting in-hospital mortality. however, rems was significantly better than gcs (p=0.035) in predicting in-hospital mortality (table 3). 4. discussion based on the results of this study, rems was better than mews, iss, and gcs in predicting in-hospital mortality occurring ≥ 24 hours after admission among adult multiple trauma patients referring to ed. based on calculated aucs, the results showed rems was an excellent predictor of inhospital mortality (auc = 0.94), and mews, iss, and gcs were good predictors of in-hospital mortality (auc = 0.89, 0.87, and, 0.85). despite advances in injury prevention and medical care, trauma deaths remain a major public health problem worldwide. to improve overall survival and management outcomes, it is important to quickly and accurately determine the severity of trauma in patients admitted to the ed. various scoring systems have been developed for the classification of injuries, which include physiologic and anatomic systems (12). each of these systems has its specific limitations and advantages, but an efficient scoring system should have fewer variables, be easy to use and be accurate, especially in emergency settings. one of the oldest trauma scores is iss. several studies have shown that iss is a valid predictor of in-hospital mortality (3, 5, 6, 8, 9). one of the important limitations of iss is the inability to be calculated in the initial evaluation of the patient. iss can be calculated after a comprehensive assessment of the patient and identification of all injuries. sevthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e64 figure 2: receiver operating characteristic (roc) curves of injury severity score (iss); glasgow coma scale (gcs); modified early warning score (mews); and rapid emergency medicine score (rems) for predicting in-hospital mortality (≥ 24 hours) of multiple trauma patients. eral scoring systems have been developed to objectively measure the initial condition of a trauma patient, and these may also serve as prognostic indicators for specific patients (912). rems and mews have acceptable predictive values for in-hospital mortality and are good choices for use in emergency settings. it seems that rems and mews scores are superior to other predictors because they both include vital signs (e.g., sbp and rr) and neurological variables (e.g., avpu, motor, and speech), which are strongly related to mortality risk. aucs of rems and mews were more than gcs, this indicates that adding parameters such as bp, hr, rr, o2 saturation, and body temperature to the level of consciousness, which is usually assessed using gcs, increases the efficiency of gcs in predicting the outcomes of traumatic patients. some of the rems and mews parameters (map or sbp, gcs or avpu and hr) were significantly associated with mortality risk, while age, oxygen saturation, temperature and rr were independent predictors of in-hospital mortality. in most previous studies, rems has been used to predict mortality in non-surgical patients. in the study conducted by olsson et al., the rems was found to be a strong predictor of both in-hospital and long-term mortality in non-surgical patients in the ed (8). goodacre et al. compared rems and raps scores in predicting in-hospital mortality of 5583 patients who were brought by the emergency ambulance and hospitalized. they found that rems is effective in predicting mortality among medical patients (13). rems can be rapidly determined in 20 minutes and has been shown to be compatible with mortality rate prediction in patients with trauma in previous studies. imholff et al. showed that a higher rems score is associated with an increase in the mortality rate of trauma patients (10). nakhjavan-shahraki et al. suggested that rems could be used to predict mortality (auc=0.93) and poor outcomes (p=0.001) in patients with trauma in emergency settings (14). the findings of the current study are consistent with those of the previous studies, which found that rems is a simple and accurate predictor of in-hospital mortality for multiple trauma patients. mews has been used to initially identify the risk of mortality and to predict the clinical outcomes of patients (1517). several studies showed that mews is useful in predicting the severity of trauma among patients. in a previous study, mews was a fair predictor of in-hospital mortality (auc, 0.79; 95% ci, 0.74-0.83) (18). in contrast, in another study, mews was a good predictor of in-hospital mortality (auc, 0.90; 95% ci, 0.88-0.92) in trauma patients (18). consistently, our results showed that mews is a good predictor (auc=0.89) of in-hospital mortality in multiple trauma patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 6 bulut et al. reported that the prognostic value of rems model for mortality of medical and surgical patients referring to eds was significantly higher than = mews (9). the results of the current study showed that rems is superior to mews and gcs in predicting in-hospital mortality for trauma patients. although the sensitivity of rems ≥ 4 and mews ≥ 3 (96.87% and 93.75) in predicting in-hospital mortality were higher than gcs ≤ 11, the specificity of gcs (93.35%) was higher than other scores. when specificity is high, it is less likely to give a false-positive. on the other hand, the sensitivity of gcs was only 56.25 %, which means that there are many false-negative results. in serious and life threatening conditions we should use tests or methods with high sensitivity to decrease false negative rates. also, in the present study, the ppv was reported to be low and the npv was reported to be high. this could be due to the low prevalence of in-hospital mortality. in this study, in-hospital mortality was 4.2%. ppv and npv are directly related to prevalence. 5. limitations our study has some limitations. first, convenience sampling method was used and the researcher was present in the ed, which may have caused selection bias. second, patients who died in less than 24 hours and those who died upon arrival were excluded; the lack of information on these patients may have caused a spectrum bias. 6. conclusion the findings of this study revealed that rems is an excellent predictor of in-hospital mortality ≥ 24 hours after admission and mews, gcs, and iss are good alternatives for predicting in-hospital mortality in multiple trauma patients. 7. declarations 7.1. acknowledgments the authors would like to express their gratitude to the staff of the eds of al-zahra and kashani hospitals, isfahan, iran. 7.2. funding this study was conducted with the support of isfahan university of medical sciences. 7.3. author contribution f.h., s.m., a.a., m.n.e., o.a., and r.a. contributed to the conception, study design, and data collection and evaluation. f.h., r.a., and a.a. contributed to statistical analysis, and interpretation of data. f.h. and r.a. were responsible for overall supervision. f.h., a.a., and r.a. drafted the manuscript, which was revised by m.n.e., o.a., and s.m. all authors performed editing and approving the final version of this paper for submission, also participated in the finalization of the manuscript and approved the final draft. 7.4. conflict of interest the authors declare no conflict of interest. references 1. heydari f, maghami m-h, esmailian m, zamani m. the effect of implementation of the standard clinical practice guideline (cpg) for management of multiple trauma patients admitted to an emergency department. advanced journal of emergency medicine. 2018;2(1):e5. 2. rhee p, joseph b, pandit v, aziz h, vercruysse g, kulvatunyou n, et al. increasing trauma deaths in the united states. annals of surgery. 2014;260(1):13-21. 3. miller rt, nazir n, mcdonald t, cannon cm. the modified rapid emergency medicine score: a novel trauma triage tool to predict in-hospital mortality. injury. 2017;48(9):1870-7. 4. park ho, kim jw, kim sh, moon sh, byun jh, kim kn, et al. usability verification of the emergency 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of trauma patients; a diagnostic accuracy study. advanced journal of emergency medicine. 2020;4(4):e89. 12. lecky f, woodford m, edwards a, bouamra o, coats t. trauma scoring systems and databases. british journal of anaesthesia. 2014;113(2):286-94. 13. goodacre s, turner j, nicholl j. prediction of mortality among emergency medical admissions. emergency medicine journal. 2006;23(5):372-5. 14. nakhjavan-shahraki b, baikpour m, yousefifard m, nikseresht zs, abiri s, razaz jm, et al. rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative study. emergency. 2017;5(1):e30. 15. fullerton jn, price cl, silvey ne, brace sj, perkins gd. is the modified early warning score (mews) superior to clinician judgement in detecting critical illness in the pre-hospital environment? resuscitation. 2012;83(5):557-62. 16. subbe cp, kruger m, rutherford p, gemmel l. validation of a modified early warning score in medical admissions. qjm. 2001;94(10):521-6. 17. salottolo k, carrick m, johnson j, gamber m, bar-or d. a retrospective cohort study of the utility of the modified early warning score for interfacility transfer of patients with traumatic injury. bmj open. 2017;7(5):e016143. 18. jiang x, jiang p, mao y. performance of modified early warning score (mews) and circulation, respiration, abdomen, motor, and speech (crams) score in trauma severity and in-hospital mortality prediction in multiple trauma patients: a comparison study. peerj. 2019;7:e7227. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e66 or i g i n a l re s e a rc h distinguishing characteristics of covid-19-associated mucormycosis; a case series seyedhadi samimiardestani1, shirin irani1∗, mehrdad hasibi2, maral seyedahadi3, shahin bastaninejad1, mohammadreza firouzifar1, mojataba mohammadi ardehali1, sina berijani1, reza erfanian1, mohammad ali kazemi4, afshar etemadi-aleagha5, abolfazl rahimi6, kourosh karimi yarandi7, samira ahadi1 1. otorhinolaryngology research center, amiralam hospital, tehran university of medical sciences, tehran, iran. 2. infectious disease department, amiralam hospital, tehran university of medical sciences, tehran, iran. 3. neurology department, amiralam hospital, tehran university of medical sciences, tehran, iran. 4. department of radiology, amiralam hospital, tehran university of medical sciences, tehran, iran. 5. department of anesthesiology, amir-alam hospital, tehran university of medical sciences, tehran, iran. 6. department of ophthalmology, faculty of medicine, tehran medical sciences, islamic azad university, tehran, iran. 7. department of neurosurgery, tehran university of medical sciences, tehran, iran. received: june 2022; accepted: july 2022; published online: 18 august 2022 abstract: introduction: since the emergence of covid-19 pandemic, several articles have reported the co-existence of mucormycosis and covid-19. this study aimed to distinguish the characteristics of covid-19-associated rhinocerebral mucormycosis. methods: in this case series, 18 patients with covid-19-associated rhinocerebral mucormycosis and unique clinical manifestations and outcomes, who were referred to amiralam hospital, a tertiary otorhinolaryngology center, tehran, iran, during the covid-19 era, were reported. results: eighteen patients with the mean age of 62.0 ± 11.6 (range: 42 – 83) years were studied (50% males). the mean time interval between diagnosis of covid-19 and first manifestation of mucormycosis was 15.5 ± 9.7 days. the most common presenting symptom was facial paresthesia (72.2%). fifty percent of patients developed frozen eye. palatal necrosis was seen in 7 cases (38.8%). remarkably, facial paralysis was observed in 5 (27.7%) patients. another notable clinical picture was cavernous sinus thrombosis, seen in 7 patients. we also had two cases of carotid artery occlusion. three patients, unfortunately, passed away. conclusion: rhinocerebral mucormycosis is one of the most important complications of covid-19 patients, especially those with underlying diseases. it seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give a patient a chance to live more. keywords: covid-19; mycoses; mucormycosis; paranasal sinuses cite this article as: samimiardestani s, irani s, hasibi m, seyedahadi m, bastaninejad s, firouzifar m, mohammadi ardehali m, berijani s, erfanian r, kazemi ma, etemadi-aleagha a, rahimi a, karimi yarandi k, ahadi s. distinguishing characteristics of covid-19-associated mucormycosis; a case series. arch acad emerg med. 2022; 10(1): e66. https://doi.org/10.22037/aaem.v10i1.1644. 1. introduction covid-19 pandemic is a crisis associated with considerable mortality and morbidity. several covid-19-associated complications have been described in the literature. bacterial and fungal co-infections are among major complications ∗corresponding author: shirin irani; amiralam hospital, north sa’di street, enghelab street, tehran, iran. fax number: +98 2166343177, email: sh_irani@razi.tums.ac.ir, orcid: https://orcid.org/0000-0002-7770-8950 . that may increase the mortality rate of covid-19 cases [1]. mucromycosis is a serious but rare fungal infection caused by mucormycetes. patients with underlying diseases, especially diabetes mellitus and immunodeficiency are highly vulnerable to mucormycosis [2]. it rarely affects immunocompetent patients [3]. rhinocerebral involvement is the classic manifestation of mucormycosis. the incidence rate of rhinocerebral mucormycosis is approximately 1.7 per 1,000,000 of normal population, and its mortality rate is estimated at 40% to 80% [4]. rhinocerebral mucormycosis usually presents in an acute setting. it originates from the nasal cavity and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimiardestani et al. 2 paranasal sinuses, and spreads to the adjacent structures including the palate, pharynx, orbits, and the brain [5, 6]. infection can spread to the meninges or the brain through the nerves, ophthalmic artery, or cribriform plate [7]. management includes antifungal therapy, surgical resection, and if possible, reversal of impaired immunity. during the covid-19 pandemic, we observed a significant rise in rhinocerebral mucormycosis in our ear, nose, and throat (ent) specialty referral center. in this study, we present clinical manifestations and outcomes of patients with covid-19-associated mucormycosis (cam). 2. methods 2.1. study design and setting this case series study was performed at amir alam hospital in tehran, iran, which is a referral center for ent conditions. during a 9-month period, from august 2020 to june 2021, patients with a diagnosis of rhinocerebral mucormycosis, who had concomitant covid-19 or were diagnosed with and/or treated for covid-19 within the past three months were included in the study. the protocol of study was approved by ethics committee of tehran university of medical sciences (ethics code: ir.tums.amiralam.rec.1401.019) and researchers adhered to the ethical considerations and confidentiality of patients’ information. 2.2. managements the diagnosis of mucormycosis was made based on the paranasal sinuses’ endoscopic findings and confirmed by positive fungal smear and culture, and histopathological documentation of fungal invasion in the paranasal sinuses and nasal cavity samples. proper antifungal agent (liposomal amphotericin b at 35 mg/kg or conventional amphotericin b at 1 mg/kg) was started during the first 24 to 48 hours of admission for all the patients. sars-cov-2 infection was confirmed using reverse transcription polymerase chain reaction (rt-pcr) and a spiral chest computed tomography (ct) scan was performed for all cases to assess lung involvement. patients with active covid-19 were transferred to the covid-19 ward and received intravenous (iv ) remdesivir at 200 mg in the first day followed by 100 mg daily for the minimum duration of five days. soon after stabilization of patients’ general condition as well as the serum glucose and electrolyte levels, endoscopic debridement of the paranasal sinuses was performed. the extent of surgical debridement was determined based on the clinical and radiological findings, ranging from simple excision of the necrotic soft tissue and bone in the turbinates and nasal septum to a more extensive procedure including partial or radical maxillectomy and debridement of pterygopalatine fossa, alveolar ridge, and palatal resection even orbital exenteration or skull base surgery. intravenous (iv ) amphotericin b was continued after surgery until a minimum total curative dose of the medication was achieved. the patients underwent weekly endoscopic examination during the admission and re-debridement was performed in the presence of any suspicious necrotic tissue. 2.3. data gathering we collected the following data for all cases: demographic data, predisposing factors, time interval between covid19 and the onset of mucormycosis, patient’s clinical manifestations and intra-operative and endoscopic findings, anatomical extension of the fungal infection, and patient’s outcome (categorized as deceased, still hospitalized, or alive—meaning no more hospitalized). 2.4. statistical analysis statistical analysis was done using spss version 23 and findings were reported as mean ± standard deviation or frequency ( 3. results 3.1. baseline characteristics of studied cases eighteen patients with diagnosis of mucormycosis and covid-19, including 9 males and 9 females, with the mean age of 62.0 ± 11.6 (range: 42 – 83) years were studied. clinical presentation, treatment, extent of surgery, and outcome of studied patients are summarized in table1 and figure 1. the mean time interval between covid-19 diagnosis and first manifestation of mucormycosis was 15.6 ± 9.7 days (range from 0 to 43 days). three patients received antifungal therapy and remdesivir simultaneously. twelve out of the 18 patients had received corticosteroids as an adjunct treatment for severe covid-19. fourteen patients were known cases of diabetes mellitus (dm), and three patients had new-onset dm. the most common presenting symptom was facial paresthesia (72.2%). among our patients, 11 (61%) had ophthalmoplegia, 10 (55.5%) had visual impairment, and 4 patients (22%) had proptosis (figure 2). fifty percent of our patients developed frozen eye. palatal necrosis was seen in 7 cases (38.8%). remarkably, facial paralysis was observed in 5 patients (27.7%) and it was a presenting symptom in all of them. interestingly, one of our patients, case no 14, had a 5-monthhistory of facial paralysis without any other mucormycosis manifestations a week after covid-19 infection. nasal obstruction was seen in 22% and dark nasal discharge was present in 16% of the patients. the presenting symptom of one patient was fever. one patient had teeth loosening due to hard palate involvement. two patients presented with loss of consciousness. another notable clinical picture was cavthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e66 table 1: baseline characteristics, treatment, extent of surgery and outcome of patients with covid-19-associated mucormycosis no./ sex/ age predisposing factors steroid hospi talization interv al (days) signs/symptoms imaging findings endoscopy findings extension of disease surgery report outcome 1/64/f dm, anemia y y 12 frozen eye, ophthalmoplegia, vision loss, proptosis, facial paralysis and paresthesia, loss of consciousness maxillary and ethmoidal sinusitis, ppf involvement, inflammation of orbital muscles, iof& sof, orbital apex, fat stranding of intraconal & extraconal fat, oval foramen, cst, carotid vasculitis, buccal abscess and gas bubble in ramus & body of mandible, inferior alveolar nerve involvement, skull base osteomyelitis no evidence of necrosis buccal, masticator, and parapharyngeal space, orbital apex, ppf, cavernous sinus antrostomy, ethmoidectomy, sphenoidotomy, buccal abscess drainage/3 times alive/9month follow-up 2/58/f dm, htn, anemia n y 14 facial paralysis and paresthesia, ophthalmoplegia, nasal obstruction, proptosis sphenoid sinus dehiscence, cst, orbital cellulitis inferior turbinate necrosis masticator and parapharyngeal space antrostomy, ethmoidectomy, sphenoidotomy, draf iib, orbital exenteration/ 3 times alive/6month follow-up 3/52/f dm, htn y y 10 fever, frozen eye, ophthalmoplegia, visual impairment, proptosis cst middle turbinate necrosis medial and superior orbital wall, ppf, cribriform plate, parasellar area and cavernous sinus, orbital apex ethmoidectomy, antrostomy, ppf debridement, draf iib, itf debridement, orbital decompression/ 2 times alive/6month follow-up 4/53/f dm y y 21 cheek paresthesia, ophthalmoplegia orbital abscess, brain micro-abscess evidence of previous antrostomy and ethmoidectomy, no necrosis medial and inferior orbital wall, ppf, cribriform plate ethmoidectomy, antrostomy, orbital decompression and abscess drainage, bilateral ppf debridement/ 2 times alive/9month follow-up 5/52/m dm, htn n y simult aneous frozen eye, vision loss, ophthalmoplegia, facial paralysis and paresthesia maxillary and ethmoidal sinusitis, cst evidence of previous sphenoidotomy and ethmoidectomy, nasal septum necrosis cst, orbit, ppf ethmoidectomy, antrostomy, bilateral ppf debridement, itf debridement, orbital decompression/ 3 times alive/8month follow-up this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimiardestani et al. 4 table 1: baseline characteristics, treatment, extent of surgery and outcome of patients with covid-19-associated mucormycosis no./ sex/ age predisposing factors steroid hospi talization interv al (days) signs/symptoms imaging findings endoscopy findings extension of disease surgery report outcome 6/68/m dm, htn y n 4 facial paralysis and paresthesia, nasal obstruction and dark nasal crust, palatal necrosis, blurred vision maxillary and ethmoidal sinusitis, nasal septum and lt. middle turbinate necrosis lt. hard palate antrostomy, middle turbinate resection, ppf debridement, partial maxillectomy, itf debridement alive/7month followup 7/82/m dm n y 5 frozen eye, ophthalmoplegia, visual loss, dark nasal crust, palatal necrosis, cheek paresthesia maxillary sinusitis and erosion, ppf, sphenoid sinus, cst nasal septum and rt. middle turbinate necrosis ppf, foramen rotundum, itf no debridement death 8/47/m dm y y 30 nasal obstruction, facial swelling maxillary & ethmoid sinus, ppf, middle and inferior turbinate necrosis ppf ethmoidectomy, antrostomy, ppf debridement/ 2 times alive/1month followup 9/68/m dm, htn, ihd, gout y n 15 days frozen eye, ophthalmoplegia, vision loss, facial paresthesia maxillary & ethmoid sinus & preantral space involvement, orbital apex, intraconal fat haziness superior, middle, and inferior turbinate necrosis ppf, middle and inferior turbinate antrostomy, middle turbinate resection, ppf debridement, partial maxillectomy, itf debridement, retrobulbar amphotericin b injection/3 times alive/still hospitalized with good condition 10/67/m dm, htn y y 10 frozen eye, ophthalmoplegia, vision loss, facial paresthesia, palatal necrosis middle and inferior turbinate necrosis ppf, superior, middle, and inferior turbinate antrostomy, middle turbinate resection, ppf debridement, partial maxillectomy, palatal debridement death 11/68/m dm, htn, ckd n y 43 facial paresthesia, tooth loosening, palatal necrosis evidence of previous antrostomy, ethmoidectomy and sphenoidotomy, palatal bone necrosis ppf, middle and inferior turbinate antrostomy, middle turbinate resection, ppf debridement, partial maxillectomy, palatal debridement alive/1month followup 12/80/f htn y y 20 necrosis of nasal septum and palate mucosal thickening in ethmoid, sphenoid & maxillary sinus, air bubbles in ppf & infratemporal & masticator space (necrotizing fasciitis), orbital apex, intraconal & extraconal space, iof, sof middle and inferior turbinate necrosis, palatal bone necrosis ppf, palatine bone antrostomy, middle turbinate resection, ppf debridement, partial maxillectomy, palatal debridement death this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e66 table 1: baseline characteristics, treatment, extent of surgery and outcome of patients with covid-19-associated mucormycosis no./ sex/ age predisposing factors steroid hospi talization interv al (days) signs/symptoms imaging findings endoscopy findings extension of disease surgery report outcome 13/54/m dm unclear y 15 frozen eye, ophthalmoplegia, vision loss, facial paresthesia, necrosis in nasal endoscopy ppf antrostomy, middle turbinate resection, ppf debridement, orbital debridement alive/2month follow-up 14/62/f dm n n 7 facial paresthesia, facial paralysis ppf, iof, foramen rotundum, vidian canal, cavernous sinus, buccal and preantral space, ica c1-c7 thrombosis no evidence of necrosis in diagnostic endoscopy middle turbinate, ppf, orbit antrostomy, ethmoidectomy, sphenoidectomy, middle turbinate resection, ppf & itf debridement, debridement of orbital floor, buccal abscess drainage/ 3 times alive/month follow-up 15/40/f dm y y 15 frozen eye, ophthalmoplegia, vision loss, proptosis, facial paresthesia ethmoid, sphenoid & maxillary sinus, cribriform plate, ppf, iof, foramen rotundum, vidian canal, buccal and preantral space, orbital apex, cavernous sinus, ica evidence of previous antrostomy, ethmoidectomy and sphenoidotomy and new necrosis in posterior septum ppf, itf fossa, rotundum foramen antrostomy, ethmoidectomy, sphenoidectomy, middle turbinate resection, ppf debridement, debridement of medial and inferior orbital rim, drainage of orbital abscess, orbital exenteration/ 3 times alive/1month follow-up 16/57/f dm y y 20 frozen eye, ophthalmoplegia, vision loss, proptosis, facial paresthesia, dark nasal crust, palatal necrosis maxillary, ethmoid, sphenoid, ppf, iof, fat stranding of pre-antral fat, orbital apex, rotundum foramen, vidian canal, fat stranding of buccal, masticator & parapharyngeal space necrosis in middle turbinate and nasal floor evidences of previous debridement in another center, ppf, septum and middle turbinate just inferior to cribriform plate antrostomy, ethmoidectomy, sphenoidectomy, middle turbinate resection, ppf debridement, debridement of medial and inferior orbital rim, drainage of orbital abscess, resection of anterior table of frontal sinus & ascending process of maxilla alive/2month follow-up this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimiardestani et al. 6 table 1: baseline characteristics, treatment, extent of surgery and outcome of patients with covid-19-associated mucormycosis no./ sex/ age predisposing factors steroid hospi talization interv al (days) signs/symptoms imaging findings endoscopy findings extension of disease surgery report outcome 17/59/f dm, htn, ihd y n 17 nasal obstruction, facial edema maxillary, ethmoid, and frontal opacification necrosis in middle turbinate maxilla, ethmoid, frontal, ppf resection of right middle turbinate, antrostomy, sphenoidotomy, anterior & posterior ethmoidectomy, frontal sinusotomy/ 2times alive/still hospitalized with good condition 18/83/m htn, dm y y 20 palatal necrosis ethmoid and sphenoid opacification, bone erosion in medial wall of orbit, infraorbital space, greater wing of sphenoid not performed (directly referred to operation room) maxillary, ethmoid & sphenoid, palate and alveolar ridge, ppf, inferior orbital fissure endoscopic maxillectomy, resection of pterygoid processes, ascending process of maxilla, inferior& medial wall of orbit, debridement of pterygoid muscles, palatal & alveolar ridge resection alive/still hospitalized with good condition cst: cavernous sinus thrombosis, dm: diabetes mellitus, htn: hypertension, ica: internal carotid artery, iof: inferior orbital fissure, itf: infratemporal fossa, lt: left, ppf: pterygopalatine fossa, rt: right, sof: superior orbital fissure; ihd: ischemic heart disease; ckd: chronic kidney disease. figure 1: percentage of different clinical presentations of patients with covid-19-associated mucormycosis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e66 figure 2: magnetic resonance imaging (mri) without contrast of patient no.1, shows orbital cellulitis, maxillary and ethmoidal sinusitis (a); left cavernous sinus thrombosis and internal carotid occlusion in patient no 15 (b); right cavernous sinus thrombosis and internal carotid occlusion in patient no 14 (c). ernous sinus thrombosis, seen in 7 patients. we had two cases of carotid artery occlusion, without significant neurological manifestations (figure 2). 3.2. outcomes three patients passed away. one of them died before any surgical intervention due to rapid progression of the disease, and the other one died the day after the extensive debridement due to necrotizing fasciitis and intracranial involvement. the third patient had died due to cardiovascular problems unrelated to mucormycosis disease, a week after the debridement. ultimately, 15 cases were discharged with prescription of oral posaconazole with favorable condition and normal sinus endoscopy. 4. discussion since the emergence of the covid-19 pandemic, several publications have reported the co-existence of mucormycosis and covid-19 disease. it seems that covid-19 infection may predispose the susceptible patients at risk of developing mucormycosis, especially in patients with dm. apart from increasing the risk of immunodeficiency, administration of corticosteroids in covid-19 patients could result in hyperglycemia, which additionally makes the patients susceptible to mucormycosis. moreover, alteration of the innate immunity due to covid-19 infection and the microangiopathies causing endothelial damage during covid-19, are other predisposing factors [8, 9]. as a tertiary ent center, we recognized a significant rise in mucormycosis during the covid19 era. almost all signs and symptoms known to be associated with rhinocerebral mucormycosis were observed in our covid19-associated mucormycosis (cam) patients. the rapid development of frozen eye was occasionally seen in mucormycosis patients before, but it seems more common in cam patients. moreover, facial paralysis is a notable manifestation in our patients. half of our patients had frozen eye at presentation and one-third had facial paralysis, which was considerably different from our pre-covid-19 experience. bayram et al. reported a case series of cam patients, in which the most common manifestation was proptosis and 63% of their patients had frozen eye. they did not report facial paralysis as a presenting manifestation of mucormycosis. in that case series, 63% of patients passed away [10]. patel et al., conducted a multicenter retrospective study in india to investigate the cam patients. among 287 mucormycosis patients, 187 (65.2%) had cam. the prevalence of cam was 0.27% among hospitalized covid-19 patients. they noted a 2.1-fold rise in mucormycosis during the study period. the most common underlying disease was uncontrolled diabetes among cam patients. covid-19 was the only underlying disease in 32.6% of cam patients. the mortality rate was 45.7% and was similar in cam and non-cam patients [11]. similarly, in our series, dm was the most common predisposing factor among cam patients: 13 patients had diabetes and 2 had new-onset diabetes after steroid administration. note that 10 patients had a history of steroid administration for treatment of covid-19. it seems that steroid administration is a double-edged sword for management of covid-19 [12]. in a multicenter series from iran, 15 patients with cam were reported. median age of patients was 52 years and 66% were male. the median time interval between diagnosis of mucormycosis and covid-19 was 7 days, and 86% of patients had diabetes mellitus, while 46.6% received intravenous corticosteroid. orbital exenteration was performed in five patients (33%), while seven (47%) died from mucormycosis [13]. another unique finding in our cases was cavernous venous sinus thrombosis (cvst). more than half of our patients developed cvst and amazingly all of them survived. to the best of our knowledge, there is no report of cvst among cam patients in the previous literature. although, there are reports of cvst among covid-19 patients [14-16]. another noteworthy finding in our cam patients was internal carotid artery (ica) occlusion. there are several reports this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimiardestani et al. 8 about ica occlusion among covid-19 patients as well as mucormycosis patients, independently [17-21]. but there were no reports of ica among cam patients, to the best of our knowledge. different studies have reported the mortality rate of mucormycosis between 40-80%, depending on the underlying conditions and extent of infection [22]. we had a significantly lower mortality rate of 16% in our study. it could be attributable to a high clinical suspicion, rapid diagnosis and intervention owing to being a referral center for otolaryngology patients. cam indeed needs multidisciplinary management and thorough and serial examination. covid-19-associated mucormycosis is a rising condition during the pandemic, and may be associated with less usual presentations; clinicians should be made aware of this unusual presentation and incidence. it seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give the patient a better chance of survival. 5. conclusion rhinocerebral mucormycosis is one of the most important complications of covid-19 patients, especially those with underlying diseases. it seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give a patient a chance to live more. 6. declarations 6.1. acknowledgments the authors would like to sincerely thank the residents and fellowship students in ent ward and operation room and anesthesiology technologists who helped in performing the surgeries of high-risk patients, peri-operation followings, and gathering the data. also, we should express our sincere thanks to dr. hojjat salmasian for english editing the manuscript. 6.2. authors’ contributions seyedhadi samimi contributed in conceptualization, data collection, and collaborated in endoscopic surgeries. shirin irani contributed in study design, data collection, data interpretation, and collaborated in endoscopic surgeries and writing the original draft of the manuscript. mehrdad hasibi contributed in conceptualization and performing the infectious consultations. maral seyedahadi contributed in conceptualization and neurologic consultations. shahin bastaninejad contributed in conceptualization and collaborated in endoscopic surgeries. mohammadreza firouzifar contributed in conceptualization and collaborated in endoscopic surgeries. sina berijani and samira ahadi, otolaryngology residents, contributed in conceptualisation, data collection, collaboration in endoscopic surgeries and writing the original draft. mojtaba mohammadi ardehali contributed in conceptualization and collaborated in endoscopic surgeries. reza erfanian contributed in conceptualization and collaborated in endoscopic surgeries. mohammad ali kazemi contributed in conceptualization and radiologic consultations. afshar etemadi-aleagha contributed in conceptualization and collaborated in anesthesia. abolfazl rahimi contributed in conceptualization and ophthalmologic consultation. kourosh karimi yarandi contributed in conceptualization and neurosurgical consultation. all authors read and approved the final manuscript. shirin irani had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. 6.3. funding and supports this project did not have any sources of financial support. 6.4. conflict of interest the authors declare no conflict of interest in this study. 6.5. data availability the authors guarantee that data of the study are available and will be provided if anyone needs them. 6.6. ethical considerations this study was approved by the ethical committee of amiralam hospital. also, all the patients’ records are protected and confidential. references 1. deshazo, r.d., k. chapin, and r.e. swain, fungal sinusitis. n engl j med, 1997. 337(4): p. 254-9. 2. shafer, w., m. hine, and b. levy, shafer’s textbook of oral pathology. 5 [sup] th ed. 2006, amsterdam: elsevier health sciences. 3. singh, j. and n.m. prasanna, phycomycosis in an apparently normal host. j otolaryngol, 1977. 6(1): p. 37-42. 4. sachdeva, k., rhino-oculo cerebral mucormycosis with multiple cranial nerve palsy in diabetic patient: review of six cases. indian j otolaryngol head neck surg, 2013. 65(4): p. 375-9. 5. hosseini, s.m. and p. borghei, rhinocerebral mucormycosis: pathways of spread. eur arch otorhinolaryngol, 2005. 262(11): p. 932-8. 6. kemper, j., et al., recovery from rhinocerebral mucormycosis in a ketoacidotic diabetic patient: a case report. j laryngol otol, 1993. 107(3): p. 233-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e66 7. bigner, s., p. burger, and p. dubois, diagnosis of cerebral mucormycosis by needle aspiration biopsy. a case report. acta cytologica, 1982. 26(5): p. 699-704. 8. saldanha, m., r. reddy, and m.j. vincent, title of the article: paranasal mucormycosis in covid-19 patient. indian j otolaryngol head neck surg, 2021: p. 1-4. 9. moorthy, a., et al., sars-cov-2, uncontrolled diabetes and corticosteroids-an unholy trinity in invasive fungal infections of the maxillofacial region? a retrospective, multi-centric analysis. j maxillofac oral surg, 2021. 20(3): p. 418-425. 10. bayram, n., et al., susceptibility of severe covid-19 patients to rhino-orbital mucormycosis fungal infection in different clinical manifestations. jpn j ophthalmol, 2021. 65(4): p. 515-525. 11. patel, a., et al., multicenter epidemiologic study of coronavirus disease-associated mucormycosis, india. emerg infect dis, 2021. 27(9): p. 2349-2359. 12. ahmadikia, k., et al., the double-edged sword of systemic corticosteroid therapy in viral pneumonia: a case report and comparative review of influenza-associated mucormycosis versus covid-19 associated mucormycosis. mycoses, 2021. 64(8): p. 798-808. 13. pakdel, f., et al., mucormycosis in patients with covid19: a cross-sectional descriptive multicentre study from iran. mycoses, 2021. 64(10): p. 1238-1252. 14. raj, a., n. kaur, and n. kaur, cavernous sinus thrombosis with central retinal artey occlusion in covid-19: a case report and review of literature. indian j ophthalmol, 2021. 69(5): p. 1327-1329. 15. khacha, a., et al., cavernous sinus thrombosis in a covid-19 patient: a case report. radiol case rep, 2021. 16(3): p. 480-482. 16. selvadurai, s. and j.s. virk, cavernous sinus thrombosis secondary to sphenoid mycetoma following covid19 infection. qjm, 2021. 114(8): p. 594-595. 17. cancer-perez, s., et al., symptomatic common carotid free-floating thrombus in a covid-19 patient, case report and literature review. ann vasc surg, 2021. 73: p. 122-128. 18. álvarez moreno, y., et al., internal carotid artery thrombosis in covid 19. colomb med (cali), 2020. 51(3): p. e504560. 19. pisano, t.j., i. hakkinen, and i. rybinnik, large vessel occlusion secondary to covid-19 hypercoagulability in a young patient: a case report and literature review. j stroke cerebrovasc dis, 2020. 29(12): p. 105307. 20. little, j.s., et al., invasive fungal carotiditis: a rare manifestation of cranial invasive fungal disease: case series and systematic review of the literature. open forum infect dis, 2019. 6(10): p. ofz392. 21. patil, a., et al., angioinvasive rhinocerebral mucormycosis with complete unilateral thrombosis of internal carotid artery-case report and review of literature. bjr case rep, 2016. 2(2): p. 20150448. 22. cornely, o.a., et al., global guideline for the diagnosis and management of mucormycosis: an initiative of the european confederation of medical mycology in cooperation with the mycoses study group education and research consortium. lancet infect dis, 2019. 19(12): p. e405-e421. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e37 or i g i n a l re s e a rc h impact of covid-19 pandemic on emergency department referrals with urologic complaints; a retrospective cross-sectional study anahita ansari jafari1, babak javanmard2, amirhossein rahavian3∗, ahmad reza rafiezadeh4, nasrin borumandnia5, seyyed ali hojjati2, seyyed mohammad hosseininia2, hormoz karami3† 1. laser application in medical sciences research center, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. urology department, shohada-e-tajrish hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. andrology research center, yazd reproductive sciences institute, shahid sadoughi university of medical sciences, yazd, iran. 4. professor alborzi clinical microbiology research center (pacmrc; henceforth), shiraz university of medical sciences, shiraz, iran. 5. urology and nephrology research center, shahid beheshti university of medical sciences, tehran, iran. received: february 2022; accepted: march 2022; published online: 17 may 2022 abstract: introduction: medical and surgical priorities were dramatically changed during the covid-19 pandemic. this study aimed to evaluate the impact of this pandemic on presentation to emergency department (ed) with urologic complaint. methods: this cross-sectional study was conducted at a tertiary urology referral center in tehran, iran. the data of all ed admissions were collected and the frequency of admissions with urologic complain and their outcomes were compared between two 90-day periods (before and during covid-19 era). results: 480 ed admissions were studied. the number of patients visiting the ed with urologic complaint during covid-19 era was significantly lower than the same period in the pre-covid-19 period (125 vs. 355 admissions; p = 0.01). the mean hospitalization days for patients in the pre-covid-19 period were significantly higher (5.6 ± 4.4 vs. 3.2 ± 4.2 days; p <0.001). the most common patient complaints before and during covid-19 period were flank pain (32.7%) and gross hematuria (32.8%), respectively. the number of patients discharged against medical advice in the covid-19 period was significantly higher than before (22 (17.6%) vs. 10(2.8%); p < 0.001). the number of patients who developed severe complications was significantly higher in the covid-19 period than in the pre-covid-19 period (p = 0.001). conclusion: during the covid-19 pandemic we were faced with decreasing frequency of admission with urologic complaint, change in the pattern of referrals, decrease in the duration of hospitalization, increase in the number of patients discharged against medical advice, and increase in the number of cases with irreversible urologic complications or complications requiring surgery due to deferred treatment. keywords: covid-19; emergency service, hospital; pandemics; urology cite this article as: ansari jafari a, javanmard b, rahavian a, rafiezadeh ar, borumandnia n, hojjati n, hosseininia sm, karami h. impact of covid-19 pandemic on emergency department referrals with urologic complaints; a retrospective cross-sectional study. arch acad emerg med. 2022; 10(1): e37. https://doi.org/10.22037/aaem.v10i1.1563. ∗corresponding author: amirhossein rahavian; andrology research center, yazd reproductive sciences institute, shahid sadoughi university of medical sciences, yazd, iran. tel: 00989134514983, email: amirrahavian@yahoo.com, orcid: http://orcid.org/0000-0003-4173-2673. † corresponding author: hormoz karami; andrology research center, yazd reproductive sciences institute, shahid sadoughi university of medical sciences, yazd, iran. tel: 00989131575705, email: hormozkarami@yahoo.com, orcid: http://orcid.org/0000-0001-7384-2944. 1. introduction pneumonia of unknown etiology was reported in china at the end of december 2019, probably related to a seafood market (1). the authorities closed the market by the 1st of january 2020 and applied strict epidemiological investigations. as a result, scientists were able to isolate and perform genome sequencing of the 2019 novel coronavirus (2019-ncov ) on the 7th of january and gave it to the world health organization this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ansari jafari et al. 2 (who) on the 12th of january 2020 (2). the first confirmed coronavirus disease (covid-19) infections in iran were announced on 19 february 2020 (3). the world health organization declared the outbreak a public health emergency of international concern on 30 january 2020 and recognized it as a pandemic on 11 march 2020 (4, 5). the covid-19 virus is arguably the most significant challenge world healthcare systems have faced in the modern era. medical and surgical priorities were dramatically changed at the time of this pandemic. to save facilities and resources for urgent cases and covid-19 patients, all outpatient and elective activities were postponed by most of the world’s hospitals (6). stricter healthcare measures were also adopted, like suspending all non-urgent elective surgeries (7, 8) and limiting inpatient and outpatient services to critically ill patients, while increasing the critical care capacity (8-10). many studies were conducted to evaluate the effect of covid-19 outbreak on the field of urology. some of them assessed the impact of covid-19 on the education of urology students and residents (11, 12), and others revealed the effect of the covid-19 pandemic on patients with non-covid-19 health problems, including urologic emergencies (13). all reported the negative effects of the covid-19 outbreak. we experienced an interesting situation in our hospital (a tertiary referral center for urology and one of the leading centers for admission of covid-19-positive patients during the covid-19 outbreak). in addition to a reduction in the number of emergency urology patients, we also encountered an increase in ill patients’ request for discharge against medical advice, even after they were told that this could endanger their lives. in this study, we attempt to evaluate the impact of the covid-19 outbreak on urology emergency patients and follow the outcomes of patients who were discharged against medical advice. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted in shohada-e-tajrish hospital, a tertiary urology referral center in tehran, iran. we reviewed the data of all patients admitted to the emergency department with urologic problems in two 90-day time periods, first, from february 20th to may 20th, 2019 (pre-covid-19 epidemic period), and the second, from february 20th to may 20th, 2020 (covid-19 epidemic period). then the frequency of ed admissions with urologic complaint and their outcomes were compared between the two studied periods and possible causes were discussed. the protocol of the study was approved by ethics committee of shahid beheshti university of medical sciences (code: ir.sbmu.retech.rec.1400.211). researchers adhered to confidentiality of patients’ information and principles of helsinki declaration regarding the ethical considerations in biomedical researches. 2.2. participants all patients who were admitted to ed with urologic complaints in those specific periods of time were included and patients who were admitted due to trauma and surgical complications were excluded. also, patients who were managed by other specialists were excluded. 2.3. data gathering using a pre-designed checklist, the patients’ demographic characteristics, chief complaints, final diagnosis, and outcomes were recorded. in addition, patients who were discharged against medical advice during these two time periods were listed, and a telephone follow-up was conducted to determine their final outcomes. the outcomes were categorized into three groups: group one, those who died due to postponing their treatment. group two included those who developed severe complications (irreversible complications or complications requiring surgery) due to deferred treatment, including renal failure, erectile dysfunction, orchiectomy, and penile chordee. group three included patients for whom a delay in treatment had no effect on their outcome or who were treated at another center. 2.4. statistical analysis the data were analyzed using spss (version 23). continuous variables are presented as mean ± standard deviation (sd). categorical variables are presented as numbers (%). statistical analyses such as chi-square and independent t-test were used. the significance level was set at 0.05. 3. results 3.1. baseline characteristics 480 ed admissions were studied. the number of patients visiting the ed with urologic complaint in the studied 90day period after the beginning of the covid-19 epidemic was significantly lower than the same period in the previous year (125 vs. 355 admissions; p = 0.01), despite the increase in total admission rate during covid-19 pandemic. the male/female ratio was similar in the pre-covid-19 period and during the covid-19(289/66 vs. 107/18, respectively; p = 0.33). total hospitalization time for patients in the pre-covid-19 period was significantly higher (5.6 ± 4.4 vs. 3.2 ± 4.2 days; p <0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e37 table 1: comparing the frequency of patients’ chief complaints before and during the covid-19 period chief complaint pre-covid-19 during covid-19 p value flank pain 116 (32.7) 22 (17.6) 0.001 gross hematuria 81(22.8) 41 (32.8) 0.032 testis pain 40 (11.3) 27 (21.6) 0.006 urinary retention 37 (10.4) 4 (3.2) 0.014 lower urinary tract symptoms 30 (8.4) 0 (0) <0.0001 luts and fever 21 (5.9) 11 (8.8) 0.297 abdominal pain 17 (4.8) 6(4.8) 0.401 nausea and vomiting 7 (2) 4 (3.2) 0.488 penile pain 6 (1.7) 10 (8) 0.002 total patients 355 (100) 125 (100) <0.001 data are presented as frequency (%). luts: lower urinary tract symptoms. table 2: characteristics of patients discharged against medical advice in the pre-covid-19 period and their three-month follow-up n age sex cc underlying diagnosis treatment* follow-up 1 14 male testis pain non testicular torsion surgery orchiectomy in another center 2 12 male testis pain non testicular torsion surgery spontaneous pain resolution 3 67 male scrotal pain dm,htn fournier gangrene surgery expired 4 30 female flank pain and fever non pyelonephritis admission and medical treatment revisit to emergency and admission 5 39 male flank pain and n&v non urethral stone surgery spontaneous stone passage 6 55 female flank pain and fever dm,ihd emphysematous pyelonephritis surgery nephrectomy in another center 7 60 male gross hematuria htn bladder mass surgery revisit 2 weeks later 8 70 male luts cva neurogenic bladder catheter insertion and evaluation revisit to another center 9 76 male testis pain and fever dm testicular abscess surgery orchiectomy 10 80 male gross hematuria prostate cancer hemorrhagic cystitis admission and evaluation relative spontaneous recovery ages are presented in years; n: number; *: recommended treatment; cc: chief complaint; dm: diabetes mellitus; htn: hypertension; ihd: ischemic heart disease; n&v: nausea and vomiting; luts: lower urinary tract symptoms. 3.2. chief complaints table 1 compares the frequency of patients’ chief complaints before and during the pre-covid-19 periods. in pre-covid19 period, flank pain (32.7%) was the most common patient complaint, followed by gross hematuria (22.8%) and testis pain (11.3%). but in the covid-19 period, gross hematuria (32.8%) was the most common complaint, followed by testis pain (21.6%) and flank pain (17.6%). the number of patients discharged against medical advice in the covid-19 period was significantly higher compared to the pre-covid-19 period (22 (17.6%) vs. 10(2.8%); p < 0.001). 3.3. discharge against medical advice and its outcomes tables 2 and 3 show the characteristics of patients discharged against medical advice in the pre-covid-19 and covid-19 periods with their three-month follow-ups, respectively. the most common reason for discharge against medical advice in the pre-covid-19 period was their willingness to seek treatment at other centers (70%), treatment being unaffordable (20%), and uncertainty about treatment staff (10%); however, during the covid-19 period, fear of getting covid19 in the hospital (80%) was the most common reason for self-discharge. the outcomes of patients discharged against medical advice in pre and during covid-19 era are compared in table 4. the number of patients in group two (patients who developed severe complications) was significantly higher in the covid-19 period compared to the pre-covid19 period (p < 0.001). 4. discussion based on the findings, during the covid-19 pandemic period we were faced with decreasing frequency of admissions due to urologic complaint, change in the pattern of referrals, decrease in the duration of hospitalization, and increase in the number of patients discharged against medical advice. the numbers of cases who developed irreversible urologic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ansari jafari et al. 4 table 3: characteristics of patients discharged against medical advice in the covid-19 period and their three-month follow-up n age sex cc underlying diagnosis treatment* follow-up 1 54 male n&v, fatigue htn,bph,dm uremia catheterization and work up renal failure & h/d 2 63 male gross hematuria bladder cancer bladder cancer recurrence admission & cystoscopy relative recovery 3 31 male flank pain & hematuria ureteral stone tul stone passage 4 64 male gross hematuria bladder mass turt relative recovery 5 86 male gross hematuria dm,cva prostate cancer admission and work up expired 6 56 male flank pain after eswl renal stone ureteral catheterization treatment 2 months later 7 72 male scrotal pain and swelling dm fournier gangrene surgery died 8 56 female flank pain ureteral stone nephrostomy insertion decreased renal function 9 46 male flank pain ureteral stone tul treatment in another center 10 70 male gross hematuria bladder cancer bladder cancer recurrence turt radical cystectomy 11 28 male penile pain/ ecchymosis penis fracture surgery penile chordee 12 12 male scrotal pain testis torsion orchiopexy orchiectomy 24 hours later 13 30 female flank pain and fever pregnancy, renal stone pyelonephritis nephrostomy insertion revisit to another center 14 52 male penile pain dm peyronie’s disease ccb injection penile chordee 15 78 male gross hematuria prostate cancer tumor progression admission and cystoscopy revisit one month later 16 32 male gross hematuria urethral wart wart excision revisit to another center 17 80 male scrotal pain and swelling colon cancer, dm fournier gangrene surgery expired 48 hours later 18 69 female flank pain renal stone tul died due to covid-19 19 70 male gross hematuria asthma bladder mass turt revisit one months later 20 69 male urinary incontinency dm,htn bph catheterization renal failure 21 15 male scrotal pain testis torsion orchiopexy orchiectomy 22 30 male penile ecchymosis penis fracture surgery erectile dysfunction ages are presented in years; n: number; *: recommended treatment; cc: chief complaint; dm: diabetes mellitus; htn: hypertension; cva: cerebrovascular accident; n&v: nausea and vomiting; bph: benign prostatic hyperplasia; h/d: hemodialysis; tul: transurethral lithotripsy; turt: transurethral resection of tumor; eswl: extracorporeal shock wave lithotripsy; ccb: calcium channel blocker. table 4: comparing the outcomes of patients discharged against medical advice between pre-covid-19 and covid-19 eras period total outcome p value group 1 group 2 group 3 pre-covid-19 10(100) 1(10) 2(20) 7(70) 0.001 covid-19 22(100) 2(9) 12(55) 8(36) p value <0.001 0.16 0.001 0.03 data are presented as frequency (%). group one: those who died due to postponing their treatment; group two: those who developed severe complications due to deferred treatment; group three: patients for whom a delay in treatment had no effect on their outcome or who were treated at another center. complications or complications requiring surgery due to deferred treatment were also increased in the covid-19 era. the covid-19 pandemic in 2020 caused a sudden and double burden on the health care systems of all countries, and different countries dealt with this situation in different ways. for example, in the field of urology, the first step was to suspend all non-urgent elective surgeries. the second step was to discharge inpatients at the first opportunity permitted by this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e37 the patient’s clinical condition (7). these steps freed up more facilities and hospital beds for covid-19 patients and decreased the length of hospital stay for patients with urological complaints. our research revealed significant reductions in emergency urologic visits to our hospital at the beginning of the covid19 pandemic. this result was confirmed by other studies in different countries (8, 13), with motterle showing that seeking care in the year 2020 (vs. 2019) was a significant predictor of admission (or:2.71). the results strongly suggest that covid-19 significantly influenced people’s urologic care-seeking behavior (14). we can conclude that the fear of being infected by covid-19 made people avoid attending health care centers unless they had no other choice, instead preferring to tolerate or treat their problems conservatively. a reduction in elective urology surgeries and visits during the covid-19 period is reasonable. however, a decrease in urology emergency visits is potentially dangerous because a delay in treatment for some patients could be life threatening or may cause severe complications. while our hospital is a urology tertiary referral center, during the covid-19 pandemic, it became a referral center for covid-19 patients. therefore, patients tended to stay in the hospital as little as possible due to fear of covid-19 infection. as a result, the mean hospital stays were reduced significantly (5.6±4.4 vs. 3.2±4.2 days, p-value <0.001), and the rate of discharge against medical advice increased significantly (17.6% vs. 2.8%, p-value: 0.001). for the first time, we followed up and compared the outcomes of patients discharged against medical advice and found that these patients had more than twice as many complications in the covid-19 period than in the pre-covid19 period, when many complications were prevented with timely procedures. since we may face similar situations in the future, we need to be prepared. many of the solutions introduced in this crisis were mainly based on prioritizing patients and surgeries (14); we would like to provide another solution. we suggest it would be better to determine a certain number of medical centers that would be able to provide the necessary emergency services to patients. the patients could then go to these “clean centers” confidently and without fear of contamination. in this plan, patients would not postpone their treatment due to fear of contamination, and performing some elective surgeries is possible. we suggest the idea of establishing “clean centers” for managing emergency patients as a viable solution for similar future situations. 5. limitations some of the limitations of our study were the short period studied in this research and the limited amount of data collected due to covid-19’s relatively short history. future studies should cover the influence of covid-19 pandemic on long-term urologic services and will be able to utilize a more extensive data set as more time passes. 6. conclusion based on the findings, during the covid-19 pandemic period we were faced with decrease in frequency of admissions due to urologic complaints, change in the pattern of referrals, decrease in the duration of hospitalization, and increase in the number of patients discharged against medical advice. the number of cases who developed irreversible urologic complications or complications requiring surgery due to deferred treatment were also increased in the covid-19 era. 7. declarations 7.1. acknowledgments we are thankful to all medical staff for their cooperating in the fight against covid-19. also, we appreciate all the efforts of personnel in charge of the hospital’s archive of medical records for helping us gather the required data. 7.2. data availability authors guarantee that data of the study are available and will be provided if anyone needs them. 7.3. authors’ contributions aad: conception and design, protocol development, gaining ethical approval, bj: researched literature and conceived the study, nb: patient recruitment and data analysis, sah and smh: collected the data; contributed data or analysis tools, hk: critical revision of the manuscript for important intellectual content, supervision, arr: wrote the first draft of the manuscript, ar: wrote the first draft of the manuscript, data analysis, supervision 7.4. funding and supports this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. 7.5. conflict of interest the authors have no conflicts of interest relevant to this article. references 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fiori c, liguori g, et al. impact of the covid-19 pandemic on urology residency training in italy. minerva urol nefrol. 2020;72(4):505-9. 12. porpiglia f, checcucci e, amparore d, verri p, campi r, claps f, et al. slowdown of urology residents’ learning curve during the covid-19 emergency. bju int. 2020;125(6):e15. 13. motterle g, morlacco a, iafrate m, bianco m, federa g, xhafka o, et al. the impact of covid-19 pandemic on urological emergencies: a single-center experience. world j urol. 2021;39(6):1985-9. 14. heldwein fl, loeb s, wroclawski ml, sridhar an, carneiro a, lima fs, et al. a systematic review on guidelines and recommendations for urology standard of care during the covid-19 pandemic. eur urol focus. 2020;6(5):1070-85. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e11 or i g i n a l re s e a rc h validation of the north american chest pain rule in prediction of very low-risk chest pain; a diagnostic accuracy study somayeh valadkhani1, mohammad jalili2∗, elham hesari1, hadi mirfazaelian2 1. emergency medicine department, kermanshah university of medical sciences, kermanshah, iran. 2. emergency medicine department, tehran university of medical sciences, tehran, iran. received: may 2016; accepted: may 2016; published online: 9 january 2017 abstract: introduction: acute coronary syndrome accounts for more than 15% of the chest pains. recently, hess et al. developed north american chest pain rule (nacpr) to identify very low-risk patients who can be safely discharged from emergency department (ed). the present study aimed to validate this rule in eds of two academic hospitals. methods: a prospective diagnostic accuracy study was conducted on consecutive patients 24 years of age and older presenting to the ed with the chief complaint of acute chest pain, during march 2013 to june 2013. chest pain characteristics, cardiac history, electrocardiogram findings, and cardiac biomarker measurement of patients were collected and screening performance characteristics of nacpr with 95% confidence interval were calculated using spss 21. results: from 400 eligible patients with completed follow up, 69 (17.25 %) developed myocardial infarction, 121 (30.25%) underwent coronary revascularization, and 4 (2%) died because of cardiac or unidentifiable causes. by using nacpr, 34 (8.50%) of all the patients could be considered very lowrisk and discharged after a brief ed assessment. among these patients, none developed above-mentioned adverse outcomes within 30 days. sensitivity, specificity, positive prediction value, and negative prediction value of the rule were 100% (95% ci: 87.35 100.00), 45.35 (95% ci: 40.19 50.61), 14.52 (95% ci: 10.40 19.85), and 100 (95% ci: 97.18 100.00), respectively. conclusion: the present multicenter study showed that nacpr is a good screening tool for early discharge of patients with very low-risk chest pain from ed. keywords: acute coronary syndrome; decision support techniques; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: valadkhani s, jalili m, hesari e, mirfazaelian h. validation of the north american chest pain rule in prediction of very low-risk chest pain; a diagnostic accuracy study. emergency. 2017; 5 (1): e11. 1. introduction acute chest pain is one of the most common chief complaints of patients presenting to emergency department (ed) (1). acute coronary syndrome (acs) accounts for more than 15% of chest pains and is prone to misdiagnosis and inappropriate discharge (2). according to several studies, this mishap takes place in 4.4% of acs cases (3). in a recent research, it has been reported that this apparently low percentage has 9.1% fatal outcome over a 30-day period (4). these concerns have made emergency physicians ∗corresponding author: mohammad jalili; emergency department, imam khomeini hospital, keshavarz blvd., tehran, iran. tel/fax: +982161192240 ; email: mjalili@tums.ac.ir lower their work-up threshold, which may in turn result in overcrowding, increased costs, and false positive test results (5). in order to reduce the risk, several decision rules have been developed to stratify patients with chest pain (2). recently, hess et al. tried to establish a decision rule for identification of very low-risk patients who can be safely discharged from ed (6-8). this so-called north american chest pain rule (nacpr) has been developed by adherence to the recommendations on prediction rules development. they proposed that patients could be discharged if they were under 40 years old with no new ischemic change on the electrocardiogram (ecg), no past history of coronary artery disease (cad), no typical chest pain, and initial troponin within normal limits. for the patients aged between 40 and 50 years, a second normal troponin level should be available for patients to be considered as dischargeable. therefore, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. valadkhani et al. 2 the present multicenter study was conducted to validate this prediction rule in two academic eds. 2. methods 2.1. study design and setting a consecutive prospective diagnostic accuracy study was conducted on adult patients who presented to the eds of imam khomeini and shariati hospitals, tehran, iran, with chest pain as their primary complaint during march 2013 to june 2013. informed consent was obtained from every patient and the data were kept confidential. the institutional review board of the hospitals and ethic committee of tehran university of medical sciences approved the study protocol. 2.2. participants all adults older than 24 years with chief complaint of anterior chest pain presenting to ed were enrolled. as in hess et al. study, patients were excluded if there was st segment elevation at least in two contiguous leads on the initial ecg, hemodynamic instability (persistent heart rate greater than 100 beats/min or less than 50 beats/min or systolic blood pressure persistently below 90 mmhg), an unreliable clinical history, a chest pain caused by trauma, a documented history of cocaine abuse (in laboratory study or clinically), a non-cardiac terminal illness, pregnancy, previous enrollment within the past 30 days, or inability to receive followup by telephone (8). studied hospitals were tertiary-care university-affiliated centers with more than 600 beds each. they have an annual ed visit rate of approximately 40,000 patients. all diagnostic tests and therapeutic procedures were performed at the discretion of the attending physician, according to routine ed practice. patients presenting to the ed with definite signs and symptoms of developing acs (e.g. st-elevation or elevated cardiac biomarkers) were consulted with a cardiologist and admitted directly to the coronary care unit afterwards. other patiens were admitted and observed in the ed. serial ecgs and cardiac markers were obtained and further decisions were made according to the results. a team of well-trained research assistants worked in a scheduled set of shifts and enrolled eligible patients. 2.3. data gathering relevant data (i.e. patient’s age and sex, history of cad, and chest pain characteristics) were recorded on specific data collection forms by research assistants. as in hess et al. study, past history of cad was defined as at least 50% coronary stenosis on angiography; demonstrated ecg changes, perfusion defects, or wall motion abnormalities on exercise, pharmacologic, or rest imaging studies; or previous documentation of acute myocardial infarction (8). according to hospital policies, ed physicians ordered both serum creatine kinase myocardial and brain isoenzymes (ck-mb; ckmb stat cobas, roche diagnostics, indianapolis, in) and troponin t (elecsys troponin t assay, roche diagnostics) for acs patients in the initial hours of admission. in this study, troponin level on arrival was used as per the original study (8). in order to follow the study protocol, if the patient was between 41 and 50 years old and the troponin level on arrival was normal, the second troponin level test was reordered 6 hours after onset of symptoms. the patient’s final diagnosis was made based on the results of cardiac biomarkers, ecg changes and angiographic findings and was gathered from patients hospital files. on day 30, one of the investigators (eh), who was blind to the patients baseline characteristics and their screening results by nacpr, contacted patients and asked about their health status, symptoms recurrence, and any diagnostic evaluation or therapeutic procedure performed after discharge. the results were recorded on a predesigned data sheet. assigning patients to one of nacpr groups was done retrospectively and no intervention was performed to implement the rule during admission. all the ecgs were reviewed by two investigators blinded to final outcome (sv, hm), and a third investigator (mj) resolved disagreement. the definition in hess et al. study was used to define ecg abnormality (8). by considering all the factors in the history and physical examination, the clinician classified the chest pain syndrome as typical (i.e. of cardiac cause) or atypical (i.e. of non-cardiac cause). 2.4. outcomes myocardial infarction (st-elevation and non st-elevation), coronary revascularization, cardiac death, and no other definite cause found in investigation were considered as 30 days outcomes. outcomes were defined same as original derivation study of nacpr (8). the mentioned outcomes were measured after comprehensive data assessment by investigators blinded to the patients nacpr screening results. 2.5. nacpr according to nacpr, two groups of patients are eligible for early discharge. the first group includes patients younger than 40 years of age with a normal primary ecg, reporting very low-risk chest pain characteristics, and without history of ischemic chest pain. the second group of patients consist of patients 41-50 years of age with normal troponin level 6 hours after the pain onset, in addition to the criteria mentioned for the first group (8). 2.6. statistical analysis minimum sample size required for the present study was calculated to be 400 cases, considering 100% sensitivity of nacpr (95% ci: 97.1 100), 20.9% specificity (95% ci: 16.9 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e11 figure 1: the study flowchart. 24.9), 0.06 p value, and 0.048 desired precision (8). standard descriptive statistics such as means and standard deviations (sds) for normally distributed continuous data, medians and inter quartile ranges for skewed continuous data, and frequencies with proportions for categorical data were calculated using spss version 21 (spss inc., chicago, il). performance of nacpr for identifying the very-low-risk patients in this study was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios using the statistical software medcalc®version 14.10.2, available online at: http://www.medcalc.org/calc/diagnostic_test.php. 3. results: 3.1. enrollment during the 4-month study period, a total of 449 patients were potentially eligible for enrollment in this study. after screening assessments, 40 of them were excluded (9 patients lacked appropriate contact information, 24 had st segment elevation at least in two contiguous leads, two were pregnant, and five patients were under 24 years of age). therefore, a total of 409 patients were finally enrolled. 400 of which had follow-up completed (figure 1). reviewing the patient records in triage revealed that 30 patients with chest pain had been missed by research assists. table 1: baseline characteristics of studied patients (n = 400) characteristic number (%) age (year) 25 39.9 25 (6.3) 40 54.9 162 (40.5) 55 69.9 147 (36.8) ≥ 70 66 (16.5) sex male 217 (53.3) female 187 (46.7) medical history diabetes mellitus 97 (24.3) hypertension 183 (45.8) hyperlipidemia 112 (28) coronary artery disease 176 (44) smoking 106 (26.5) family history of cad 8 (2) abnormal ecg st segment change 78 (19.5) t wave inversion 169 (42.3) total 169 (42.3) troponin enzyme level normal 299 (74.8) abnormal 101 (25.3) type of chest pain typical 264 (66) atypical 136 (34) cad: coronary artery disease; ecg: electrocardiogram. 3.2. baseline characteristic of patients the mean age of the 400 enrolled patients was 56.77 ± 12.52 (25 87) and 213 (53.3%) cases were male. the baseline characteristics of patients are summarized in table 1. most of the patients were in 40 55 age group (40.5%). hypertension was the most common risk factor (45.5%) and 169 (42.3%) patients had abnormal ecg. 264 (66%) cases of chest pain were typical. patient dispositions were as follows: 23 (5.8%) cases were discharged from ed, 359 (89.8%) cases were admitted to coronary care unit (ccu), and 18 (4.5%) patients left ed against medical advice. 3.3. screening characteristics of rule based on the results of screening with nacpr, 34 (8.5%) cases were in very low-risk group for developing 30 day adverse outcomes and were eligible to be discharged from ed. table 2 summarizes 30 day adverse outcomes of studied patients. 194 (48.5%) of them had experienced adverse outcomes. table 3 shows the screening performance characteristics of the prediction rule. the area under the roc curve was 0.726 (0.681 0.770), figure 2. excluding the second troponin level test in 40-50 year old patients did not change the rule’s performance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. valadkhani et al. 4 figure 2: receiver operating characteristics (roc) curve of north american chest pain rule. table 2: 30 day outcomes of studied patients outcomes n (%) myocardial infarction st segment elevation 15 (3.8) non st segment elevation 54 (13.5) revascularization percutaneous coronary intervention 86 (21.5) coronary artery bypass graft 35 (8.8) survival dead 4 (1) alive 396 (99) table 3: screening performance characteristics of north american chest pain rule in prediction of very-low-risk patient with chest pain characteristics value (95% confidence interval) sensitivity 100 (87.35 100.00) specificity 45.35 (40.19 50.61) positive predictive value 14.52 (10.40 19.85) negative predictive value 100 (97.18 100.00) positive likelihood ratio 0.17 (0.12 to 0.23) negative likelihood ratio 0 accuracy 0.726 (0.681 770) 4. discussion: based on the results of the present study, nacpr has 100% sensitivity and negative predictive value in predicting very low-risk patient for developing 30 day adverse outcomes of mi, revascularization, and death among those presenting to ed with chest pain. having used nacpr, 34 patients (8.50%) would have been eligible to be included in the very low-risk group and could be discharged from the ed. none of the 166 patients who developed aforementioned outcomes within 30 days would have been included in the very-low-risk group by implementation of this rule. in our study, sensitivity and negative likelihood ratio were similar to those found by hess et al. and mahler et al. (100% and 0%). the specificity in our study (14.53%) was lower than the original study (20.90%) but higher than mehler et al. study (5.6%) (8, 9). this difference may be due to the type of patients and the center where our patients were selected. interestingly, all the patients in 40-50 with abnormal second troponin had another criterion of the rule that excluded them from early ed discharge. as a result, the rule performance would not change after excluding the second troponin measurement. clinical decision rules are developed in order to facilitate the decision making process in common and important clinical conditions. acute chest pain has a high prevalence, which calls attention to develop rules. these rules use easily obtainable elements in history, clinical examination, and simple tests, to safely rule out hazardous conditions (2). data in the united states showed that approximately 2% of patients with acs are misdiagnosed and inappropriately discharged from the eds (3). furthermore, several patients suspected of having acs are ultimately diagnosed with non-cardiac chest pain and sent home after time-consuming and costly workups (10). this sheds light on the necessity of a set of screening criteria with high sensitivity, to minimize misrate, and with high specificity, to prevent excessive costs arising from diagnostic procedures and long hospital stays. in 1990s, some rules for cardiac care unit admission were developed based on observation with 3% misrate (11, 12). later on, biomarkers were employed to develop rules (e.g. timi risk score) and in order to improve this process, several standards were defined. in this regard, according to systematic reviews, many of chest pain decision rule derivation studies are retrospective with methodologic flaws (13, 14). in a prospective study, hess et al. derived a clinical decision rule for identification of patients with very lowrisk chest pain who could be safely discharged from ed without further objective cardiac testing such as stress tests (8). by adhering to the correct methodology, the researchers followed 2718 patients for 30 days. 336 patients experienced adverse cardiac events. by analyzing the data, they proposed that patients could be discharged if they were under 40 with no new ischemic change present on the ecg, no past history of cad, without typical chest pain, and initial troponin within normal limits. for the patients between 40 and 50, a second normal troponin level should be available after 6 hour of symptom onset for patients to be considered as dischargeable. recently vancouver chest pain rule was developed according to methodological standards by utilizing biomarkers (15). christenson et al. used past history and initial ecg to discharge patients younger than 40. for older patients they proposed using pain characteristics and ck-mb level. this study was 98.8% sensitive and 32.5% specific for prediction of adverse cardiac events within 30 days. jalili et al. found sensitivity of 95.1% and specificity of 56.3% for vancouver this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e11 chest pain rule. the ppv and npv were fairly similar (2). in addition to having lower yields in comparison to nacpr, there are some debates over this rule. for example, hess et al. study showed that some elements in vancouver chest pain rule have insufficient inter-observer reliability (8). recently, mahler et al. compared the nacpr with heart score for major cardiac events and unstructured clinical evaluation (9, 16). since the study was a secondary analysis on another study, definition of elements of the rule (i.e. ecg interpretation, chest pain description, past history of cad, and serial troponin timing (0 and 3 hours)) differed from hess et al. study. interestingly, the sensitivity and negative likelihood ratio of this modified nacpr was 100% and zero, respectively. the results showed that both rules were comparable with unstructured clinical evaluation and had the acceptable misrate of less than 1%. 5. limitations: our study faces some limitations. although this rule assesses chest pain, like hess et al. study, we did not study unstable angina independently. in addition, non-chest pain presentation of cardiac origin was not included in the rule, which precludes its application in these patients. during the study period, inter-observer agreement was not assessed in our study in regard to gathering patient information by research assistants and ecg assessment by hm and sv, which in turn may increases the risk of performance bias. as shown in the hess et al. study, several other factors such as presence or absence of observation units can also affect the costs. however, due to lack of accurate and detailed financial records, we were not able to determine the use of financial resources and find out if costs had been minimized by early discharge of very-lowrisk patients. another limitation in our result interpretation is 10% failed enrollment or follow up. in addition, even the most accurate rules are unlikely to be applied in practice if they are not considered reasonable by the end-user, therefore, these rules should consist of simple and sensible elements (17). end-user (physician) contentment was not assessed in our study either. 6. conclusion: in summary, our study proved that the prediction rule proposed by hess et al. is a sensitive decision tool for diagnosing very-low-risk chest pain patients who can be discharged early from the ed. 7. appendix 7.1. acknowledgements we express our acknowledgment to the ed staff of imam khomeini and shariati hospitals, tehran, iran. 7.2. authors contribution sv and eh acquired the data, mj conceived the study and supervised, and hm acquired the data and drafted the manuscript. all the authors contributed substantially to its revision. mj takes responsibility for the paper as a whole. 7.3. conflict of interest none. 7.4. funding none declared. references 1. niska r, bhuiya f, xu j. national hospital ambulatory medical care survey: 2007 emergency department summary. natl health stat report. 2010;26(26):1-31. 2. jalili m, hejripour z, honarmand ar, pourtabatabaei n. validation of the vancouver chest pain rule: a prospective cohort study. academic emergency medicine. 2012;19(7):837-42. 3. pope jh, aufderheide tp, ruthazer r, woolard rh, feldman ja, beshansky jr, et al. missed diagnoses of acute cardiac ischemia in the emergency department. new england journal of medicine. 2000;342(16):1163-70. 4. schull mj, vermeulen mj, stukel ta. the risk of missed diagnosis of acute myocardial infarction associated with emergency department volume. annals of emergency medicine. 2006;48(6):647-55. 5. pines jm, szyld d. risk tolerance for the exclusion of potentially life-threatening diseases in the ed. the american journal of emergency 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erwin p, jaffe as, hollander je, et al. diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome in the emergency department setting: a systematic review. cjem. 2008;10(04):373-82. 14. steurer j, held u, schmid d, ruckstuhl j, bachmann lm. clinical value of diagnostic instruments for ruling out acute coronary syndrome in patients with chest pain: a systematic review. emergency medicine journal. 2010:emj. 2010.092619. 15. christenson j, innes g, mcknight d, thompson cr, wong h, yu e, et al. a clinical prediction rule for early discharge of patients with chest pain. annals of emergency medicine. 2006;47(1):1-10. 16. keller t, zeller t, peetz d, tzikas s, roth a, czyz e, et al. sensitive troponin i assay in early diagnosis of acute myocardial infarction. new england journal of medicine. 2009;361(9):868-77. 17. toll d, janssen k, vergouwe y, moons k. validation, updating and impact of clinical prediction rules: a review. journal of clinical epidemiology. 2008;61(11):1085-94. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e25 https://doi.org/10.22037/aaem.v9i1.1177 or i g i n a l re s e a rc h the geographical distribution of probable covid-19 patients transferred by tehran emergency medical services; a cross sectional study peyman saberian1,2, hosein rafiemanesh3, mostafa sadeghi4, parisa hasani-sharamin5, fatemeh dadashi5, alireza baratloo1,6∗ 1. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 2. department of anesthesiology, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. 3. department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 4. department of anesthesiology and critical care, shariati hospital, tehran university of medical sciences, tehran, iran. 5. tehran emergency medical service center, tehran, iran. 6. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: january 2021; accepted: february 2021; published online: 10 march 2021 abstract: introduction: mapping of covid-19 infection in the city can help us know more about how the disease is distributed and spread. this study was conducted to investigate the geographical distribution of probable covid19 patients who were transferred to destination hospitals by emergency medical services (ems) in the first wave of the epidemic, in tehran, iran. methods: this cross-sectional study was performed based on recorded missions during the first 3-month period of the pandemic in tehran, iran. all probable cases of covid-19 who were transferred to the hospitals following contact with tehran ems during the study period were enrolled. arc-gis software was utilized to draw the distribution map of the contact places of the cases. results: in this study, the data of 4018 patients were analyzed (60.9% male). the mean age of the patients was 54.1 ± 20.7 years; and the mean age of the patients had increased with time during the studied 3 months (p = 0.003). the average incidence rate of this disease in tehran during the study period was 4.6 per 10,000 population. generally, the lowest and highest raw frequencies of tehran covid-19 contamination were seen in municipal districts 21 and 4, respectively. the raw frequency of cases during the 3-month study period also showed that the highest number of cases in tehran occurred in municipal districts 5 and 4, respectively. conclusion: in the present study, using geographic information systems (gis), geographical distribution map of covid-19 in tehran, iran, during the first 3 months of the pandemic was drawn. keywords: emergency medical services; geographic information systems; covid-19; tehran; iran cite this article as: saberian p, rafiemanesh h, sadeghi m, hasani-sharamin p, dadashi f, baratloo a. the geographical distribution of probable covid-19 patients transferred by tehran emergency medical services; a cross sectional study. arch acad emerg med. 2021; 9(1): e25. 1. introduction since the outbreak of a new coronavirus, sars-cov-2, various studies have been designed and performed to assess different dimensions of its resulting disease, named covid19 (1). certainly, the most important part of these stud∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, hasanabad square, tehran, iran. email: alirezabaratloo@yahoo.com / arbatratloo@sina.tums.ac.ir; tel: +989122884364, orcid: 0000-0002-4383-7738. ies is devoted to finding a treatment or vaccination, however, other aspects of this pandemic are also of particular importance and require research. one of the important aspects of this pandemic may be the epidemiological aspect of the disease and how the epidemic spreads geographically (2, 3). geographic information system (gis) is one of the tools used to evaluate such information, which can show the patterns of epidemic progression in geographical units (4). indeed, health professionals have long considered conventional mapping and more recently the gis, as critical tools in tracking and combating contagion. researchers have stated this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 2 that, like in the previous epidemic of sars-cov in 2003-2004, seasonal flu, and etc., gis can be very helpful in the current pandemic and provide a lot of information at different levels to its users. for example, online mapping of infected cases in the city can help to know more about how the disease is distributed and spread. there is also a wide range of gis applications for mapping and tracking the sars-cov-2 epidemic and its related events (5). the world health organization (who) has put monitoring of the disease around the world on the agenda to provide a clear vision of the pandemic. this vision contains information on the overall status of patients, involved countries, the number of deaths, and countries with the highest rate of mortality. such information can provide an overview of the disease for health policymakers, researchers, and people around the world to make appropriate decisions based on the circumstances (6). considering the above reasons, this study was conducted to investigate the geographical distribution of probable covid19 patients who were transferred to destination hospitals by tehran emergency medical services (ems) in the first phase of the epidemic and describe how the disease spread geographically in tehran in the first phase. 2. methods 2.1. study design this cross-sectional study was conducted in tehran, iran. it was performed using the previously recorded information in the registry system of tehran ems in a 3-month period from february 20, 2020, to may 20, 2020. first month was esfand,1398 (in solar calendar) compatible with february 20, 2020-march 19, 2020; 2nd month was farvardin, 1399 (in solar calendar) compatible with march 20, 2020-april 19, 2020; and 3rd month was ordibehesht, 1399 (in solar calendar) compatible with april 20, 2020-may 20, 2020. in order to conduct the study, the necessary permission to access the information was obtained from tehran ems center and also the study proposal was approved by the ethics committee of tehran university of medical sciences (code: ir.tums.medicine.rec.1399.413). confidentiality of information was maintained and therefore all information was recorded, analyzed, and reported anonymously. 2.2. study population census method was used for sampling and the study population in this study included all probable cases of covid-19 (based on who definition (7)) who were transferred to the hospitals following contact with the ems during the study period and their information was recorded in the registry system. if the patient’s file was incomplete or the patient had died before the emergency technicians arrived, the case was excluded. also, patients with other complaints who were transferred to the hospital by the tehran ems, and were diagnosed with covid-19 during the diagnostic procedures were not included. 2.3. definitions according to the 2016 census, tehran has a population of 8,680,000, with district 9 and district 4 being the least and the most populated geographical districts among the 22 municipal districts, respectively (figure 1). in order to cover this population over the area of 730 square kilometers in tehran, tehran ems center had 217 stations and 250 ambulances in the city, and 2200 technicians throughout the duration of this study. according to the policies adopted by the ministry of health and medical education following the covid-19 epidemic, there was a strong recommendation that patients should be transferred by the ems, and it was frequently announced through the public media, and therefore, all patients quarantined at home after the diagnosis was confirmed, contacted the ems as soon as symptoms worsened or a new complaint was raised. at first, these patients were transferred only to a limited number of medical centers (n=10) that were allocated to these patients, but later, following the change of instructions by the iranian ministry of health, they were transferred to all general medical centers in the city. according to the statistics of the iranian ministry of health and medical education, the number of patients with covid-19 who were transferred to hospitals was about 22% of the total number of infected cases in tehran. 2.4. data gathering the data were extracted from patients’ files and tehran ems registry system using a researcher-made checklist. this checklist consisted of two main parts: the first part included the demographic data and information related to the disease (age and sex); the second part included the temporal-spatial information of the missions (the caller’s location at the time of contact with the ems dispatcher). 2.5. statistical analysis in this study, the number of probable covid-19 cases was calculated and presented as the raw frequency and the monthly incidence rate for the population of each district. to calculate the incidence rate based on the population as well as other population indicators such as population per hectare and working population, the census statistics of 2016 were used. arc-gis software was utilized to draw the distribution map of the cases. also, anova test was used to examine the relationship between quantitative variables (such as mean age) in the 3-month study period, and the pearson correlation was used to examine the ecological correlation between the number of cases with the population per hectare of each district and the working population of districts. anathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e25 lytical analyzes were performed at a confidence level of 95% using stata software version 14. 3. results in this study, the data of 4018 patients with a probable diagnosis of covid-19 in tehran (divided into 22 districts) during the first three months of the covid-19 epidemic were studied (60.9% male; male/female ratio = 1.6). the frequency of patients in different age groups by sex is reported in table 1. the mean age of the studied patients was 54.1 years (sd = 20.7). the pyramid of the age-sex frequency during the first three months of the covid-19 epidemic is shown in figure 2. in general, the number of patients, both male and female, was lower in the age group <35 years. the mean age of the studied patients in the 1st, 2nd and 3rd month of the study was 53.2 (sd = 20.1), 54.5 (sd = 21.0), and 56.0 (sd = 21.8) years, respectively (p = 0.003). the geographical distribution of the studied patients in different months is shown in figure 3. generally, the lowest and highest raw frequencies of tehran covid-19 contamination were seen in municipal districts 21 and 4, respectively. the districts 4 and 5 accounted for 18.6% of the total infected cases. in all districts, the number of cases was higher for males than for females, and in districts 12, 17 and 21, the number of infected males was more than twice the females. the raw frequency of cases in the 3 studied months also showed that the highest number of cases in tehran occurred in municipal districts 5 and 4, respectively. in 1st month, the number of cases had reached less than 100 in all districts, most of which were seen in the districts 4, 14, and 15 with 46, 47, and 63 cases, respectively. also, the overall number of male cases in all districts was higher than female cases during the three studied months. however, the difference between the number of male and female cases decreased in the 3rd month and in some districts (2, 3, 6, 7, 16, 19, and 22) the number of contaminations in females was higher than males. the number of cases in most districts of tehran decreased from the 1st to the 3rd month, and this decrease was greater for districts with more cases (such as district 4 and 5). in district 22, the changes during the 3 months of the study were not significant. 3.1. incidence rate based on population in total, for the whole of tehran, the incidence rate of covid19 during the 3 studied months was 4.6 cases per 10,000 population. in the 1st, 2nd, and 3rd month, this rate was 2.16, 1.78, and 0.70 per 10,000 population, respectively. the lowest and highest incidence rates in tehran during the studied 3 months were in the municipal districts 21 and 12 with 3.27 and 7.18 per 10,000 population, respectively. in district 12, incidence rate in the 1st month and the 2nd month was 3.45 and 2.53 per 10,000 population, respectively. in the 2nd month, district 22 had the highest monthly incidence rate (1.43 per 10,000 population; figure 4). during the 3 studied months, the incidence rate in males and females was 5.67 and 3.41 cases per 10,000 population, respectively. the monthly incidence rate for males in 1st, 2nd, and 3rd month was 2.79, 2.10, and 0.77 per 10,000 males, respectively, and for females these rates were 1.42, 1.39, and 1.60 per 10,000 females, respectively. there was no significant relationship between the population per hectare in each district with the number of cases, although this correlation was generally positive, and in districts with a higher population per hectare the number of cases was higher (r = 0.212, p = 0.343) (figure 5). there was a significant relationship between the working population of each district with the number of cases (r = 0.886, p <0.001), this strong significant positive correlation was also seen in each of the 3 months of study separately (figure 6). 4. discussion in the present study, it was found that based on the probable cases registered in tehran ems center, the average incidence rate of this disease in tehran was 4.6 per 10,000 population during the study period, and the lowest and highest incidence rates belonged to the municipal districts 21 and 12, respectively. although in this study the correlation between population per hectare in each district and the number of cases was generally positive, and the districts with a higher population had more cases, no statistically significant relationship was found between them. to the best of our knowledge, there is no similar article, conducted on the same population, because no one else has access to this information, which was extracted from tehran ems registry bank. there is one that was performed to give a spatial analysis of covid-19 spread from february 19th to march 18th, at a province level in iran, which is interestingly conducted by ramírez-aldana et al. (8), who are mexican authors! however, they found that there was a considerably higher density of covid-19 patients around tehran province. hazbavi et al. assessed covid-19 incidence pattern, using geo-database, during seven successive periods in iran, again at province level. they found that in the second month of the pandemic (february 18–march 19 of 2020), tehran province, with more than 1000 infected cases, was one of the highly affected provinces of iran. tehran had the most deaths with an increasing trend for all the study periods (9). these findings confirm the special importance of the study of tehran in this regard. during the period of the present study, the highest number of patients with covid-19 were transferred to hospitals by ems system from districts 4 and 5 of tehran. reviewing the maps, it can be also seen that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 4 the incidence of this disease in the third month of the study, which was in fact 3 months after the official announcement of the first case in iran, had decreased significantly. also, districts 21, 22, and 9 of tehran had the lowest number of cases throughout the study, which is consistent with the population of the districts. in other words, districts with lower population had always accounted for a smaller number of cases. moreover, 4 densely populated districts of tehran, including districts 4, 5, 2, and 15 always had the highest number of cases. analysis of incidence rate based on the population showed that the spatial changes of the epidemic started from the central districts of the city, and in the second and third months it expanded throughout tehran, especially to the districts that were not involved. meanwhile, districts such as 1, which is considered as one of the districts with a high level of socio-economic status, always had a lower rate of incidence for the population; so that in the first and second months it had the least number of infections, and in the third month the number of cases was between 0.5 to 1 per 10,000 population. the same pattern can be seen in other districts with higher socio-economic status like districts 2 and 5. this finding suggests that socioeconomic factors may also be influential in the speed of covid-19 spread. in contrast, some central districts of tehran, such as district 12, had the highest number of cases, which can be attributed to having the greatest number of scientific, commercial, etc. centers, and traffic. however, the central parts of tehran, which usually have the highest population density during working hours, such as districts 6, 10, 11, and 12 were in a better situation than expected, which may be the result of shutting down of businesses and markets, and traffic reduction in these particular districts. besides, it should be acknowledged that many businessmen and people who commute to the mentioned districts do not inhabit there and travel from other areas of tehran or even the suburbs of tehran. although infected cases were more commonly >35 years old, the disease was found in all age groups. the mean age of patients during the first three months of the covid-19 epidemic was increasing with time and the difference between the mean age of patients between the 1st and 3rd month was statistically significant. this could be due to a change in the age pattern of infected cases, assuming the call pattern has not changed during the 3 months. table 1 and figure 1 demonstrate that the age-sex pattern of missions has changed from the young to the elderly and from male to female during the 3 months of the study. in this study, no significant correlation was found between population density, based on population per hectare, of each district and the number of cases. probably one of the reasons for this finding is the lower number of residential use; for example, although districts 21 and 22 are larger, they do not necessarily have a lower population density, and they are probably not much different from smaller districts in terms of population density in residential areas. the additional space of larger districts can be attributed to non-residential areas that have no effect on population density. the results of this study showed a strong positive correlation between the number of the working population in each district and the number of cases. this correlation was seen in the overall duration of the study as well as for each month of the study, separately. this finding shows that the working population can be one of the most important factors in the spread of the covid in society. it suggests that one of the ways to control the epidemic is by paying attention to the working population and develop preventive protocols for this population. considering the fact that tehran ems is a concentrated system and is responsible for providing services to the entire metropolis of tehran, by developing appropriate policies to create online and instant management dashboards and using the calls and missions of this center, the spread of the epidemic can be assessed in different districts and the necessary preventive strategies to control and restrain the spread of the virus can be implemented. once the situation in different districts of tehran is determined in terms of the number of inhabitant cases in each district, it is time to identify and analyze the factors that caused these fundamental and tangible differences by planning appropriate studies. 5. limitation the database is based on cases transferred by the ems so it does not include all diagnosed cases because some people went to hospitals and medical centers without contacting ems, whose data was not included. moreover, cases who were transferred to the hospital by the ems with other chief complaints and were diagnosed with covid-19 during the diagnostic procedures were not included in the study. on the other hand, those who were transferred as probable covid19 cases but the disease was subsequently ruled out were not identified. 6. conclusion in the present study, using gis, geographical distribution map of covid-19 in tehran, iran, during the first 3 months of the pandemic was drawn. the mapping can help compare the 22 municipal districts of tehran in this regard and hopefully be suitable for use by governmental health managers. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e25 7. declarations 7.1. acknowledgments we would like to express our gratitude to the pre-hospital and hospital emergency research center affiliated to tehran university of medical sciences. 7.2. authors’ contribution the conception and design of the work by ps, phs, ms and aa; data acquisition by phs, hr and fd; analysis and interpretation of data by hr and aa; drafting the work by hr, phs, fd and aa; revising it critically for important intellectual content by ps and ms; all the authors approved the final version to be published; and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work will be addressed. 7.3. competing interests none. 7.4. funding this study was funded with a grant from tehran ems center. references 1. vahidi e, jalili m. why covid-19? advanced journal of emergency medicine. 2020;4(2s):e36. 2. rezaei m, nouri aa, park gs, kim dh. application of geographic information system in monitoring and detecting the covid-19 outbreak. iranian journal of public health. 2020;49:114-6. 3. sarwar s, waheed r, sarwar s, khan a. covid-19 challenges to pakistan: is gis analysis useful to draw solutions? the science of the total environment. 2020;730:139089. 4. kolivand p-h, faraji sabokbar h, saberian p, bahmanabadi m, hasani-sharamin p, baratloo a. spatial analysis of geographic distribution and accessibility of suspected acute stroke patients transferred to acute stroke centers by emergency medical services in tehran, iran: a cross-sectional study. iranian red crescent medical journal. 2020;22(7):e101502. 5. kamel boulos mn, geraghty em. geographical tracking and mapping of coronavirus disease covid-19/severe acute respiratory syndrome coronavirus 2 (sars-cov-2) epidemic and associated events around the world: how 21st century gis technologies are supporting the global fight against outbreaks and epidemics. international journal of health geographics. 2020;19(1):8. 6. haining rp, haining r. spatial data analysis: theory and practice: cambridge university press; 2003. 7. who. public health surveillance for covid19: interim guidance 2020 [available from: https://www.who.int/publications/i/item/who-2019ncov-surveillanceguidance-2020.7. 8. ramírez-aldana r, gomez-verjan jc, bello-chavolla oy. spatial analysis of covid-19 spread in iran: insights into geographical and structural transmission determinants at a province level. plos neglected tropical diseases. 2020;14(11):e0008875. 9. hazbavi z, mostfazadeh r, alaei n, azizi e. spatial and temporal analysis of the covid-19 incidence pattern in iran. environmental science and pollution research. 2020:1-11. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 6 table 1: frequency of each age group in males and females in each of the three studied months and the overall period of the study age group first month second month third month total male, female, male, female, male, female, male, female, n=1499 n=805 n=1169 n=777 n=419 n=354 n=3087 n=1936 0-25 47 (3.1) 23 (2.9) 56 (4.8) 27 (3.5) 22 (5.3) 16 (4.6) 125 (4.0) 66 (3.4) 25-35 172 (11.5) 79 (9.8) 145 (12.4) 74 (9.5) 58 (13.8) 23 (6.7) 375 (12.1) 176 (9.1) 35-45 267 (17.8) 144 (17.9) 208 (17.8) 122 (15.7) 77 (18.4) 45 (13.0) 552 (17.9) 311 (16.1) 45-55 312 (20.8) 155 (19.3) 185 (15.8) 126 (16.2) 59 (14.1) 43 (12.5) 556 (18.0) 324 (16.7) 55-65 240 (16.0) 136 (16.9) 163 (13.9) 136 (17.5) 61 (14.6) 58 (16.8) 464 (15.0) 330 (17.0) 65-75 205 (13.7) 115 (14.3) 177 (15.1) 119 (15.3) 51 (12.2) 61 (17.7) 433 (14.0) 295 (15.2) 75-85 186 (12.4) 108 (13.4) 152 (13.0) 106 (13.6) 60 (14.3) 70 (20.3) 398 (12.9) 284 (14.7) 85-102 70 (4.7) 45 (5.6) 83 (7.1) 67 (8.6) 31 (7.4) 38 (11.0) 184 (6.0) 150 (7.7) mean±sd 54.3±18.1 55.5±18.3 54.8±19.8 57.2±19.0 54.3±20.3 60.8±19.8 54.5±19.1 57.1±19.0 data are presented as frequency (%). sd: standard deviation. figure 1: distribution of the population in 22 districts of tehran based on the 2016 census. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e25 figure 2: the pyramid of the age-sex frequency of missions in tehran (22 districts) during the first three months of the covid-19 epidemic. figure 3: geographical distribution of the crude number of covid-19 patients during the first three months of the covid-19 epidemic in tehran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 8 figure 4: geographical distribution of incidence rate (per 10,000 population) of covid-19 during the first three months of the covid-19 epidemic in tehran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e25 figure 5: correlation between population per hectare in the districts of tehran and the number of missions during the first three months of the covid-19 epidemic. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 10 figure 6: correlation between the employed population in each district of tehran with the number of missions during the first three months of the covid-19 epidemic. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e7 https://doi.org/10.22037/aaem.v9i1.1004 rev i ew art i c l e burnout among healthcare providers of covid-19; a systematic review of epidemiology and recommendations mehrdad sharifi1, ali akbar asadi-pooya2,3, razieh sadat mousavi-roknabadi1∗ 1. emergency medicine department, faculty of medicine, shiraz university of medical sciences, shiraz, iran. 2. epilepsy research center, shiraz university of medical sciences, shiraz, iran. 3. jefferson comprehensive epilepsy center, department of neurology, thomas jefferson university, philadelphia, pa, usa. received: november 2020; accepted: november 2020; published online: 10 december 2020 abstract: introduction: in the current systematic review, we intended to systematically review the epidemiology of burnout and the strategies and recommendations to prevent or reduce it among healthcare providers (hcps) of covid-19 wards, so that policymakers can make more appropriate decisions. methods: medline (accessed from pubmed), science direct, and scopus electronic databases were systematically searched in english from december 01, 2019 to august 15, 2020, using mesh terms and related keywords. after reading the title and the abstract, unrelated studies were excluded. the full texts of the studies were evaluated by authors, independently, and the quality of the studies was determined. then, the data were extracted and reported. results: 12 studies were included. five studies investigated the risks factors associated with burnout; none could establish a causal relationship because of their methodology. no study examined any intervention to prevent or reduce burnout, and the provided recommendations were based on the authors’ experiences and opinions. none of the studies followed up the participants, and all assessments were done according to the participants’ self-reporting and declaration. assessing burnout in the hcps working in the frontline wards was performed in four studies; others evaluated burnout among all hcps working in the regular and frontline wards. conclusion: paying attention to the mental health issues, reducing the workload of hcps through adjusting their work shifts, reducing job-related stressors, and creating a healthy work environment may prevent or reduce the burnout. keywords: burnout, professional; covid-19; coronavirus; health policy; workforce cite this article as: sharifi m, asadi-pooya a a, mousavi-roknabadi r s. burnout among healthcare providers of covid-19; a systematic review of epidemiology and recommendations. arch acad emerg med. 2021; 9(1): e7. 1. introduction burnout is a global health concern that affects physicians, nurses, and other healthcare providers (hcps), and has been the focus of recent debates (1, 2). world health organization (who) recognized burnout as a syndrome and based on international classification of diseases (icd)-11 it is defined as: ”burnout is caused by chronic stress in the workplace which is not managed successfully and is characterized by three dimensions: 1) feeling of energy loss or fatigue; 2) increased mental distance from one’s job or negative feelings or pessimism about the job; and 3) reduced professional ef∗corresponding author: razieh sadat mousavi-roknabadi; emergency medicine department, faculty of medicine, shiraz university of medical sciences, namazi hospital, postal code: 71937-11351, shiraz, iran. email: mousavi_razieh@sums.ac.ir, orcid: 0000-0001-9483-8848, tel: +989131563018. fectiveness”. burnout refers specifically to job-related issues and should not be used to describe experiences in other areas of life (3). burnout symptoms include frequent absences from work, a tendency to leave the profession, decreased self-esteem, and drug abuse, among others (4). burnout is closely associated with reduced patient care level, increased incidence of medical errors, and lower patient safety (5-7). on the other hand, burnout may have negative effects on hcps’ quality of life (6). various studies have examined burnout in different health groups. a meta-analysis that was performed a decade ago, showed that 11% of nurses had experienced burnout worldwide (2). many physicians may have similar experiences (1). since the beginning of the year 2020, the world has been experiencing an outbreak and a pandemic of coronavirus disease (covid-19) that is caused by sars-cov2. by september 06, 2020, 216 countries were affected, nearly 27 million people were infected, and about 900,000 had died (8). since this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 2 the onset of the pandemic, hcps, especially those working at emergency departments and departments that were specially devoted to treat covid-19 patients, have faced a wide range of occupational stressors and a higher than usual workload; prolonged wearing of personal protective equipment (ppe), excessive heat caused by extra clothes, dehydration, poor nutrition, lack of enough sleep, and fatigue have predisposed hcps to burnout (9). on the other hand, constant exposure to the suffering and death of patients and the constant need to sympathize with patients and their family members have caused extra mental health problems (10-13). with the onset of the pandemic, various studies have examined burnout among hcps working in covid-19 wards (1115). in the current systematic review, we intended to systematically review the epidemiology of burnout and the strategies and recommendations to prevent or reduce it among hcps of covid-19 wards, so that policymakers can make more appropriate decisions. 1.1. data sources in this systematic review of the literature, we searched medline (accessed from pubmed), science direct, and scopus electronic databases from december 01, 2019 to august 15, 2020, using mesh terms and the following keywords: (“covid–19” or “covid19” or “corona” or “coronavirus” or “sars-cov–2”) and (burnout) and ("medical staff" or "health personnel"). google scholar and researchgate.net were also used to access other articles in english. to ensure literature saturation, the reference lists of the included studies or relevant reviews identified through the search were scanned. 1.2. study eligibility criteria we focused on the studies on the epidemiology of burnout and the strategies and recommendations to prevent or reduce it among hcps. articles were excluded if they were not relevant to the epidemiology of burnout, or to strategies and recommendations to prevent or reduce it, or were performed before the covid-19 pandemic, through reading the title and the abstract. 1.3. participants, and interventions the target population were all hcps of covid-19 wards (physicians, nurses, etc.). moreover, we wanted to find which solutions or interventions are effective in preventing or reducing burnout among them. 1.4. study appraisal and synthesis methods then, full texts of the studies were evaluated by two authors (ms, rsm); they decided whether these met the inclusion criteria, independently. the quality of the studies was determined according to the american academy of neurology criteria for classification of evidence in causation studies (16). they resolved any disagreement through discussions, and finally the articles were selected based on consensus. neither of the authors were blind to the journal titles or to the study authors or institutions. the following data were extracted from the included studies and recorded in a microsoft excel sheet, 2016: study authors, methods, main findings, and recommendations. this systematic review was reported according to the recommendations of the preferred reporting items for systematic reviews and meta analyses (prisma) statement (17) (figure 1). 2. results in total, 12 studies were included (9, 11, 12, 14, 15, 18-24). table 1 shows the summary of these studies and their quality. eleven studies were original articles with cross-sectional design; one study provided a conceptual paradigm for showing the relationship between acute stress disorder, posttraumatic stress disorder, and burnout (18). five studies investigated the risk factors associated with burnout (11, 18, 19, 23, 24); none could establish a causal relationship because of their methodology. no study examined any intervention to prevent or reduce burnout, and the provided recommendations were based on the authors’ experiences and opinions. none of the studies followed up the participants, and all assessments were done according to the participants’ self-reporting and declaration. eight studies used the maslach burnout inventory (mbi) tool to evaluate the burnout (9, 11, 12, 14, 15, 19, 21-24); one used a questionnaire that was designed by the researchers (11); one used stanford professional fulfillment index (pfi) (17); and one study used a non-validated questionnaire (23). web-based questionnaires through e-mail or social media were used in five studies (11, 15, 18, 19, 23). assessing burnout in the hcps working in the frontline wards was performed in four studies (9, 12, 14, 22); others evaluated burnout among all hcps working in the regular and frontline wards (10-13, 15, 18-21, 23, 24). four studies evaluated burnout among all hcps, including physicians, nurses, technicians, paramedics, and other staff [1795 hcps in all taiwan hospitals (11); 1153 hcps in frontline wards in italy (12); 920 hcps in turkey (15); and 1422 hcps in spain (20)]. three studies were conducted on nurses and physicians (14, 22, 23). in addition to the above-mentioned studies, we found 11 articles including opinions, editorials, or letters (6, 10, 13, 2532). table 2 shows the summary of these latter studies. we categorized the related factors and the recommendations in five areas: 1. personal characteristics, 2. mental health status, 3. digital technologies, 4. workplace conditions and organizational behavior, and 5. the society (see also table 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e7 3. discussion in this systematic review, twelve studies were found, which were about the epidemiology of burnout, or strategies and recommendations to prevent or reduce burnout among hcps of covid-19 wards. most of the studies used the mbi tool to evaluate the burnout. mbi is one of the most common tools and the gold standard to measure burnout among staff, based on self-reporting using a likert scale (33, 34). our results showed that none of the studies were interventional, and none of them followed the participants. although we categorized the related factors in 5 areas, most of the studies focused on the workplace conditions and organizational behavior as well as mental health status. the results showed that burnout among hcps working in the frontline wards was assessed in four studies; others evaluated burnout among all hcps working in the regular and frontline wards. there are conflicting findings concerning the rate and epidemiology of burnout among hcps working in covid19 wards. a study on 1,153 italian healthcare professionals found that those who were directly involved with covid-19 patients experienced higher levels of job-related stress, somatic symptoms, and burnout. burnout, particularly emotional fatigue and depersonalization, was directly associated with the experience of at least one somatic symptom (such as changes in eating habits, difficulty sleeping, and muscle tension) during the past 4 weeks (12). in another study, 40.3% of the hcps of covid-19 wards, particularly nurses (45%) and physicians (31%), experienced burnout (11). a study from turkey found that burnout rate was higher among the staff of emergency departments, ambulances, and intensive care units (icus), who were in the first line of combat against covid-19 (15). one study reported that trainees who were exposed to covid-19 patients had higher rates of burnout compared to those in the non-exposed group (18). another survey found that nurses had experienced the following: 60.5% emotional fatigue, 42.3% depersonalization, and 60.6% decreased self-adequacy (19). in contrast to the above-mentioned studies, one study reported that those working in covid-19 wards had significantly lower levels of burnout compared with physicians and nurses working at other wards; the former hcps felt higher levels of control over their work, they were more aware of the preventative policies and procedures, and were supported by the healthcare system. furthermore, the staff working at the covid-19 wards felt more valued (14). another study on first-line residents (e.g., emergency medicine, radiology, and icu), showed that 76% of them had burnout, which was lower compared to that among residents at other wards (rate of 86%) (9). further studies are needed to clarify the frequency of burnout among hcps working under different circumstances during the covid-19 pandemic. various studies have mentioned several associated factors for burnout. hcps may experience higher levels of workload, are engaged with strict organizational regulations, have less time to deal with their job challenges, and the knowledge in the field is continuously evolving (35). furthermore, during the covid-19 pandemic, an uncertain prognosis of patients; lack of enough medical resources for diagnosis, treatment, and prevention; problems related to protecting healthcare providers from getting infected due to inadequacy of ppe; rapid change in public health-related policies; decreased income and economic recession; and conflicting information announced by officials have been major stressors that certainly may increase the risk of burnout (36). health managers and policymakers’ awareness of burnout is important in prevention and appropriately addressing it. a meta-analysis (2018) showed that resilience reduces burnout (37). therefore, during the covid-19 pandemic, it is necessary to recognize the factors associated with burnout and also identify the ways to deal with them. different studies have suggested various methods to prevent or reduce burnout. these methods may be divided into two categories: individual methods and organizational (system-based) approaches (9, 13, 14, 19, 24, 26). some studies reported that women have higher levels of emotional fatigue than their male counterparts (12, 26). also, men may experience fewer somatic symptoms (12). one study showed that being a woman is a risk factor for experiencing burnout among hcps working in acute critical care division (11). on the other hand, another study reported that burnout was not associated with gender (37). it was also reported that burnout was more common among hcps who had a child or a family member older than 65 years or with a chronic illness, due to fear of transmitting the infection (15). on the other hand, maintaining physical and emotional hygiene is an effective strategy to reduce burnout. happiness, regular exercise, drinking water, and having a good rest may increase the immunity and keep the person away from the disease (11, 24, 25, 38) (11, 25, 38). therefore, simple measures such as providing a resting facility and the possibility of taking a shower at the workplace may be effective (38, 39). interaction with family members and loved ones (40) and social support by the family (19, 29, 30) are other effective measures in reducing burnout. one of the important factors associated with burnout is the mental health status (33). burnout is a multi-dimensional response to job stressors. these stressors may be physiological, emotional, or interpersonal (41). burnout may lead to increased rates of psychological problems, suicide, and substance use among hcps (20). obligation to provide selfless service to the community may lead to neglecting their own physical, mental, social, and emotional health among hcps (10). improving work schedules, promoting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 4 self-management, teaching physical, mental, and emotional self-care, and starting mindfulness-based stress control activities are among the effective techniques to prevent or reduce burnout (10, 13, 28). providing counseling and support systems, as well as holding support meetings for covid-19 treatment teams are other effective interventions (12, 26, 27, 35). hcps should be heard, protected, prepared, and supported by their organizations. digital technologies may be a causative factor for burnout and also may be used to reduce burnout. in recent years, the role of digital technologies in providing health services has expanded. during the covid-19 pandemic, registry systems and electronic health record (ehr) systems have been used widely (32). these systems should serve physicians and hcps, but at the same time, ehr systems monitor physicians’ performance and their qualifications. therefore, instead of spending time to provide health services to patients, physicians have to enter the data into the ehr; as a result, they spend more time at the hospital and stay away from their families; these may cause burnout (6). on the other hand, digital technologies, such as mobile applications and social media, can be used to provide mental health services and increase the empowerment of hcps (32). talking about concerns with colleagues and friends, which can be achieved through web-based social media, is an appropriate way to reduce the stress (9). also, the use of digital communication platforms, such as whatsapp, allows physicians to access each other more easily, share information, and have immediate access to valid and updated information. burnout is often influenced by organizational behaviors. changing the behaviors that may cause burnout and adopting healthier behaviors is essential. this can only happen if there are organizational interests to meet these challenges (10). a meta-analysis showed that workplace interventions were directly associated with a reduction in the burnout scores (35). therefore, along with other individual measures, interventions to improve the workplace and organizational environment have significant effects on promoting work culture and relieving workplace stress (9, 13, 20, 24, 26). the number of work experience years, the number of working hours per week, more night shifts per week, the frequency of working over the weekends, having a coworker who is suspected or has a confirmed diagnosis of covid-19, and the number of staff members in each team may be associated with burnout (24, 42). organizational strategies to create a capable environment to reduce burnout could include the following interventions: improving workflow management, organizing services with an emphasis on reducing workload, improving communication skills, arranging discussion meetings, increasing interoperability, providing the opportunity for having adequate rest and exercise, holding workshops on coping skills, decreasing the clinical demand via schedule changes, and increasing teamwork (19, 25, 31, 32). developing clear and up-to-date guidelines and protocols for different situations, as well as practical training about protective interventions are among interventions that may increase the sense of safety, assurance, and control (9, 24, 26, 31). finally, the who has stated that an imbalance between effort and reward may lead to feelings of injustice or incompetence, which in turn leads to the feeling of anger that may be directed against the supervisor or co-worker (43). to reduce burnout, there should a balance between giving and taking, stress and relaxation, and work and home (44). burnout may be associated with social support outside the family (19). social interactions of hcps are effective in reducing burnout (29, 30). wearing face protection equipment may lead to deterioration of the interpersonal relations and interactions due to difficulty in face recognition. to solve this problem, it was recommended to install photos of the staff on their clothes (9). 4. conclusion awareness of healthcare managers and policymakers from burnout among hcps, who are working at covid-19 wards, and administration of appropriate solutions to prevent or reduce the burnout are necessary. paying attention to the mental health issues, reducing the workload of hcps through adjusting their work shifts, reducing job-related stressors, and creating a healthy work environment may prevent or reduce burnout. future, large and multicenter studies on hcps of covid-19 wards are necessary to identify the frequency, associated factors, and effective preventative strategies of this phenomenon. 4.1. implications of key findings the available early-stage and low-quality evidence cannot provide convincing support in favor of or against a particular recommendation to prevent or reduce burnout in hcps of covid-19 wards. this is mainly because of the heterogeneity with respect to the participants and applied tools, different suggestions, absence of any intervention, and not following the participants. however, the results of this study showed that the policymakers can take measures to prevent or reduce burnout in the five introduced areas. however, more large and interventional studies are highly recommended to identify effective solutions and measure their effectiveness. 4.2. standard protocol approvals, registrations, and patient consents the shiraz university of medical sciences institutional review board approved this study and systematic review (ir.sums.med.rec.1399.322). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e7 4.3. systematic review registration number the review protocol was not previously registered. 4.4. availability of data and material data sharing is not applicable to this article. 4.5. ethical issues this study was approved by the vice-chancellor of research and technology (grant no. 23376), as well as the local ethics committee (ir.sums.med.rec.1399.322) of shiraz university of medical sciences. 5. declarations 5.1. acknowledgment this study was approved by the vice-chancellor of research and technology (grant no. 23376), as well as the local ethics committee (ir.sums.med.rec.1399.322) of shiraz university of medical sciences. the authors thank all the hcps fighting covid-19 around the world. 5.2. author contributions study concept and design: mehrdad sharifi, razieh sadat mousavi-roknabadi acquisition of data: mehrdad sharifi, razieh sadat mousaviroknabadi interpretation of data: mehrdad sharifi, ali akbar asadipooya, razieh sadat mousavi-roknabadi drafting the manuscript: mehrdad sharifi, ali akbar asadipooya, razieh sadat mousavi-roknabadi final approval: mehrdad sharifi, ali akbar asadi-pooya, razieh sadat mousavi-roknabadi 5.3. funding shiraz university of medical sciences (grant no. 23376). 5.4. conflict of interest there is no conflict of interest. references 1. imo uo. burnout and psychiatric morbidity among doctors in the uk: a systematic literature review of prevalence and associated factors. bjpsych bulletin. 2017;41(4):197-204. doi: 10.1192/pb.bp.116.054247. pubmed pmid: 28811913. 2. woo t, ho r, tang a, tam w. global prevalence of burnout symptoms among nurses: a systematic review and meta-analysis. j psychiatr res. 2020;123:9-20. doi: 10.1016/j.jpsychires.2019.12.015. pubmed pmid: 32007680. 3. organization wh. burn-out an "occupational phenomenon": international classification of diseases 2019. available from: https://www.who.int/mental_health/evidence/burnout/en/. 4. maunz s, steyrer j. 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pubmed central pmcid: pmcpmc7269422. 41. albott cs, wozniak jr, mcglinch bp, wall mh, gold bs, vinogradov s. battle buddies: rapid deployment of a psychological resilience intervention for health care workers during the covid-19 pandemic. anesth analg. 2020;131(1):43-54. epub 2020/04/30. doi: 10.1213/ane.0000000000004912. pubmed pmid: 32345861; pubmed central pmcid: pmcpmc7199769. 42. kamal ah, bull jh, wolf sp, swetz km, shanafelt td, ast k, et al. prevalence and predictors of burnout among hospice and palliative care clinicians in the us. journal of pain and symptom management. 2020;59(5):e6-e13. 43. burton j. healthy workplace framework and model: background and supporting literature and practice world health organization2010. 44. maslach c. burnout: the cost of caring: ishk; 2003. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 8 table 1: articles included in this systematic review and their main findings author methods main findings recommendations level of evidence dimitriu mc, et al. (2020)(9) cross-sectional study to compare the frequencies of burnout syndrome among 50 medical residents working in the frontline wards (30 emergency, 10 radiology and 10 intensive care unit) and 50 medical residents working in normal hospital wards (25 surgery, 15 obstetrics and gynecology, 10 orthopedics) during the covid-19 pandemic. • burnout was significantly more frequent in medical residents in normal wards (86%) compared to medical residents working in frontline (76%). • effective measures must be taken at the institutional and individual levels. • balance between giving and taking, stress and relaxation, and work and home. • the shift program must be planned in a way that respects the epidemiological timing (incubation period or quarantine time). • periods of rest and relaxation must be observed. • practical training sessions should be held on the use of ppe. iii sung cw (2020)(11) cross-sectional study to evaluate burnout, anxiety symptoms, acute stress disorder, and health literacy and promotion among 1,795 hcps in taiwan hospitals during the covid-19 pandemic. • 45% of nurses and 31% of physicians suffered from burnout. • burnout was: o 30% higher in hcps who worked in the acute critical care division (acc). o 87% higher in hcps who had taken care of suspected or confirmed cases. o 9 times higher in hcps with depressive disorder. o 24% lower in hcps who had higher health literacy and engagement in promotion activities. • hcps in the acc had higher risk of burnout if they: o were female o were a physician or nurse o had no previous experience with sars or mers o had severe anxiety • avoiding excessive and unnecessary preventative measures. • ordinary or modest self-protection measures rather than an aggressive change of daily habits may be a better strategy. • health literacy and health promotion behavior. • being joyful, exercising, drinking water, and having a good sleep. iii barello s, et al. (2020)(12) cross-sectional study to describe the levels of burnout and physical symptoms of 1,153 italian hcps in frontline directly involved in the care of patients with covid-19. • >33% had high emotional exhaustion scores. • 25% had high levels of depersonalization. • 15% had low levels of personal satisfaction. • 45% experienced at least one physical symptom in the previous 4 weeks (change in food habits, difficulty falling asleep and muscle tension). • higher levels of burnout were associated with a more frequent experience of symptoms. • females showed higher levels of emotional exhaustion. • physicians experienced symptoms less frequently than nurses. • provide timely counseling services and support systems to mitigate the massive impact. iii wu y, et al. (2020)(14) cross-sectional study to compare the frequency of burnout between physicians and nurses working in usual and frontline wards, including 190 participants, 96 of whom worked in the frontline wards. • the frequency of burnout was significantly lower in the frontline group than in the usual wards group in the past 2 months during the covid-19 pandemic. • hcps in usual wards may have perceived less control over new policies and procedures. • hcps in frontline may have felt closer to the key decision makers and have had access to more timely and accurate information. • much attention is paid to those who work directly with infected patients. • 76% of participants from the frontline strongly disagreed or disagreed that he/she felt more burnout now compared with before the covid-19 pandemic. • participants continuing to work in their usual wards were more worried about themselves or a family member becoming infected. iii this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e7 table 1: articles included in this systematic review and their main findings author methods main findings recommendations level of evidence shahin t, et al. (2020)(15) cross-sectional study to compare anxiety and burnout levels between hcps working in emergency service with other hcps in turkey during the covid-19 pandemic. • the burnout score of pandemic area and the intensive care unit (icu) workers were similar to those in the emergency service and ambulance. • the emotional score of the emergency and ambulance workers was higher. • the burnout score of pandemic fields and icu workers was significantly higher than radiology, laboratory, and office workers. • burnout was higher in women and hcps who lived with their relatives >65 years of age. • burnout in doctors and nurses was higher than other hcps. • ppe was associated with higher burnout score. iii kannampallil tg, et al. (2020)(18) cross-sectional study to investigate the effects of learner exposure to covid-19 patients in their clinical roles on their mental health and wellness outcomes in 393 physician trainees (residents and clinical fellows) in the united states. • the exposed group had a higher level of burnout compared to the non-exposed group. • multivariate regression showed that trainees who were exposed to covid-19 patients reported significantly higher burnout. • normalize feelings of emotional distress and reduce stigma by encouraging discussion of the stressors of clinical work. • provide programs that increase accessibility to mental health services for trainees. • provide childcare options for married trainees at night shifts and long hours duties. iii hu d, et al. (2020)(19) cross-sectional study to evaluate mental health (burnout, anxiety, depression, and fear) and the associated factors among 2,014 frontline nurses who were caring for covid-19 patients in china. • about half of the nurses reported moderate and high job burnout, 60.5% emotional exhaustion, 42.3% depersonalization, and 60.6% personal accomplishment. • emotional exhaustion was positively correlated with skin lesion and negatively correlated with self-efficacy, resilience, intra-family social support, and extra family social support. • depersonalization was negatively correlated with resilience, intra-family social support, and extra-family social support. • personal accomplishment was positively correlated with self-efficacy, resilience, intra-family social support, and extra-family social support. • improve mental health • build self-efficacy and resilience • provide sufficient social support • ensure frontline work willingness iii this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 10 table 1: articles included in this systematic review and their main findings author methods main findings recommendations level of evidence restauri n and sheridan ad (2020)(20) a comprehensive study to provide a conceptual paradigm for understanding the relationship between burnout, acute stress disorder, and post-traumatic stress disorder (ptsd); as well as an evidence-based review and recommendations for system-based interventions that may reduce physicians’ stress. • increased exposure to stress and trauma due to acutely increased workplace stress resulting from the pandemic, combined with underlying baseline burnout, may result in rising rates of ptsd among physicians. • causes of burnout: o lack of job control o excessive workload o prolonged work stress o imbalance between demands and skill set • burnout consequences: o decreased productivity o decreased quality of patient care o decreased patient satisfaction o increased turnover o increased medical error o increased substance abuse o increased depression o increased suicide o disrupted relationships organization-directed interventions are more effective in preventing and reducing burnout: • decrease the clinical demand via schedule changes • increase team work • increase job control • increase shared decision making • mindfulness and cognitive behavioral therapy. • support an infrastructure that allows hcps to work from home to decreases exposure and concerns about infection. • education about burnout via expert panel discussions and accessing mental health to increase awareness and early intervention, and reduce stigma. • increase the sense of safety in the workplace with clear communication from leadership to increase the sense of safety and stability, and increase team work. • improve a culture of psychological safety in the workplace. • individual interventions; such as micropractices (strategies requiring just a few seconds to manage stress). iv lucenomoreno l, et al. (2020)(21) cross-sectional study to analyze posttraumatic stress, anxiety, depression, and associations between burnout and resilience in 1,422 spanish hcps during the covid-19 pandemic • anxiety and depression were positively and significantly related to emotional exhaustion and depersonalization. • high scores on emotional exhaustion and depersonalization are risk factors for mental health, with resilience and personal fulfilment being protective variables. • resilience is a protective factor. • promote resiliency iii zerbini g, et al. (2020)(22) cross-sectional study to compare the psychosocial strain in 111 hcps [75 nurses (45 covid-19 wards vs. 30 regular wards) and 35 physicians (17 covid-19 wards vs. 18 regular wards)] during the covid-19 pandemic. • participants with increased scores for exhaustion, depression, anxiety, and stress reported a higher fear of being infected. • feeling more stressed at work was associated with burnout. • fear was correlated with higher emotional exhaustion and depersonalization. • nurses working in the covid-19 wards reported higher levels of exhaustion. • physicians had similar scores regardless of the type of ward. • the most common causes for psychosocial burden: o job strain (increased workload, organizational changes in working team, conflicts with colleagues) o uncertainty about the future (healthcare system and economic crisis) o concerns about one’s safety and the safety of the family • family, friends, and leisure time lead to more resilience. • social support was one of the most important resources to cope with the psychological burden following the pandemic. • provide social support • arrange more off-time for spending time with family and friends. • provide psychological support • reduce working hours. • keep working teams stable. • improve communication and recognition. • provide clear and available guidelines. iii this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e7 table 1: articles included in this systematic review and their main findings author methods main findings recommendations level of evidence morgantini la, et al. (2020)(23) cross-sectional study to describe the burnout’s contributing factors among 2,707 hcps (physicians such as residents and fellows; nurses) during the covid-19 pandemic, from 60 countries. • 51% reported burnout (higher than previously reported rates) due to high workload, job stress, and time pressure, and limited organizational support. • burnout was associated with: o work impacting household activities o feeling pushed beyond training o exposure to covid-19 patients o making life-prioritizing decisions o adequate ppe o high-income compared to lowand middle-income countries actions from healthcare institutions and other governmental and non-governmental stakeholders, included: • providing additional training and mental health resources • providing updated guidelines • strengthening organizational support for hcps’ physical and emotional needs • supporting family-related issues (e.g. helping with childcare, transportation, temporary housing, wages) • acquiring ppe • methods focused on mindfulness, stress management and small group discussion. iii wan z, et al. (2020)(24) cross-sectional study to evaluate the status of burnout and anxiety among 1,011 chinese nurses working for at least one week during covid-19 epidemic and the influencing factors. • the predictive factor for emotional exhaustion: o 5 years or less working experience o living in hospital dormitory o 3 or more night shifts weekly o a better level of knowledge of covid-19 o having confirmed or suspected medical staff with infection around • for cynicism: o intermediate tile o personnel agency o working in isolation ward o living in hospital dormitory o 3 or more night shifts weekly o a level of knowledge of covid-19 o having confirmed or suspected medical staff with infection around • for personal accomplishment: o no siblings o living at a hotel o 9 or more hours of daily work o level of knowledge of covid-19 o having confirmed or suspected medical with infection staff around • perform series of measures to care for hcps, such as increasing remuneration package, implementing first-line personnel life security, and strengthening personal protection. • increase the knowledge and skills of hcps who care for covid-19 patients. • managers pay more attention to the hcps safety, and take protective measures and care for them. iii this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 12 table 2: articles in the format of opinion, editorial, letter, or prospective author aim main findings recommendations hartzband p and groopman j (2020)(6) to describe the causes and solutions of burnout in physicians during the covid-19 pandemic. • recommendations have targeted the doctor, proposing exercise classes and relaxation techniques, snacks and social hours for decompressing, greater access to child care, hobbies to enrich free time, and ways to increase efficiency and maximize productivity. • intrinsic and extrinsic motivators would have additive or synergistic effects. • other opinions stated that tangible extrinsic motivators, such as monetary rewards, can paradoxically weaken intrinsic motivation. • three pillars support professionals’ intrinsic motivation and psychological wellbeing: autonomy, competence, and relatedness. • physicians and their family and friendships suffer from the electronic health records’ demands that invade doctors’ homes and consume the time enjoyed in vital relationships, worsening emotional exhaustion. • give back autonomy, competence, and relatedness to physicians. upadhyay p (2020)(10) to describe the burnout in hcps in nepal and its factors and recommendation during the covid-19 pandemic. the positive factors for burnout: • long working hours • increasing bureaucratic tasks • continued exposure to human suffering and death • constant need to be compassionate to patients and their family members • increase violence against hcps and feeling unappreciated • lack of ppe, respirators, and hospital infrastructure to support the increasing hospitalizations • moral and ethical dilemma during decision making process • a sense of guilt and regret for the general lack of preparedness to support the patients • fear for one’s life and safety • delay in instituting measures to effectively address the problems • inappropriate work culture • hierarchical structure of the medical fraternity • neglecting physical, mental, social, and emotional wellbeing by hcps • mandated time away from work (especially for frontline hcps) • practice mindfulness • assess own physical and mental health by hcps • train physical, mental and emotional self-care • change in one’s lifestyle • implement self-driven technique • establish a healthier work environment • change work culture fessell d and cherniss c (2020)(13) to describe micropractice for burnout prevention and emotional wellness during the covid-19 pandemic. • institutional and individual interventions for addressing burnout and promoting wellness: • decreased workload, improved work schedules and electronic health record, mindfulness-based stress reduction, and personal coaching. • physicians enjoy highly actionable tools that require minimal time to learn and implement (micropractices). • micropractices only require a few seconds to a few minutes to implement. although many structural and cultural changes are needed, micropractice is a suitable strategy to prevent burnout. • suitable times for micropractices: o hand hygiene for self-awareness and self-management. o when logging into the electronic health records. o hearing the concerns of family or friends o when waiting at a red light o before answering e-mails or texts o when brushing teeth • take a moment to name one’s emotions, especially challenging emotions. • write down three good things. • share the personal practices around burnout prevention and wellness in a workshop setting. • do diaphragmatic breathing. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e7 table 2: articles in the format of opinion, editorial, letter, or prospective author methods main findings recommendations houtrow aj (2020)(25) to compare symptom management vs. treating the cause of burnout. • when hcps cannot act in accordance with the moral obligations to the patients, it may result in psychological distress. • symptom interventions, such as mindfulness training are valuable and important, but a shift to addressing the root causes is definitely essential. • hcps suffer when the public health response is inadequate. • use mindfulness practices, relaxation techniques, exercise • promote clinician well-being shah k, et. al (2020)(26) to describe measures to address the physicians’ burnout during the covid-19 pandemic. • physicians, residents, fellows, and other hcps experience a varying degree of burnout. • physician burnout factors: o work factors: high workloads and prolonged work hours o personal characteristics: work-life imbalance, inadequate support, sleep deprivation o organization factors: workload expectations, insufficient rewards, and interpersonal communication negative leadership o other factors: lack of control over procedures, infection control measures, the false notion of safety precautions, poor communication and directives, lack of preparedness and emotional support, inadequate ppe, and perceived fatality • empower physicians by providing essential resources adequately (ppe, beds, medicines, ventilators, educational guidelines, and research updates). • provide consistent and updated guidelines regularly to staff for managing patients through triage based on the case priority and severity. • recruit additional hcps and administrative staff • facilitate the setup of telemedicine and telepsychiatry services. • provide support with clear communication from the leadership regarding quarantine directives, guidelines, and management protocol. • restrict excessive workload by scheduling breaks and limiting work hours in emergency and intensive care units. • provide regular psychosocial support, essential basic needs, mindfulness sessions, and resilience training. • daily screening of vital signs, possible symptoms of infection, and signs of burnout. • train the expertise of the residents and fellows as a frontline worker to handle patients. • protect and support residents and fellows by creating an action plan and temporarily deferring the rules for training and board eligibility. nadler b, et al. (2020)(27) to describe the strategies for supporting oncology hcps during the covid-19 pandemic. the wellness of hcps is a spectrum, from engagement to burnout; that individual characteristics, experiences and organizational factors can influence one’s position on this spectrum. interventions to decrease burnout: • organizational level: 5 principles (“hear me,” “protect me”, “prepare me”, support me” and “care for me”). • “create” (compassion and resilience team-building): pairs a psychosocial services professional with clinical managers to offer support and implant low-dose interventions into clinical teams using a coaching and psychological first aid model. • a toolkit with information on accommodation, grocery delivery, safety, coping and mental health resources. janeway d (2020)(28) to describe the role of psychiatry in treating burnout among nurses during the covid-19 pandemic burnout is related to: • lack of health insurance • lack of resiliency • poor communication skill • lack of safe environment to express their anxieties, fears, grief, and hopeless/helpless feelings • poor self-care skills • using psychiatrists and mental health professionals (mental health services) • consultation liaison (cl) psychiatry provide assistance through liaison meetings, stress management programs, and curbside consults to help reduce the risk of burnout. • cl provide a safe environment for hcps to express their anxieties, fears, grief, and hopeless/helpless feelings in addressing the mental health needs of their patients. • journal club meetings • providing better communication skills • stress management programs (one or two sessions, an 8-12week program or open weekly sessions) • improve relaxation skill • resiliency training program • improving cognitive, behavioral, self-care skills, yoga, tai chi • grief counseling • brainstorming around ways to change workplace and workload • building workload and organizational management skills • music and art therapy • writing workshops ong am (2020)(29) to describe the impact of the covid-19 pandemic on medical education and resident burnout in a postgraduate program. • burnout risk factors among residents: o separation from their colleagues and families o loss of autonomy o disruption of training and reduction the usual cases and procedures • residents mentioned fear for their own health as they were in the frontline. • plan a 24-hour hotline with a psychologist and weekly mindfulness sessions over video conference. • create a clear and open channel of communication between the program director and the residents. • communicating with their colleagues over social media or email frequently. • implement a ‘no questions asked’ policy in the event of any resident taking sick leave. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 14 table 2: articles in the format of opinion, editorial, letter, or prospective author methods main findings recommendations ong am (2020)(30) to describe burnout in a gi fellowship program during the covid-19 pandemic. • the cause of burnout: o reduction in elective procedures o concern about the training program o concern about maintaining their procedural skills, due to deployed on isolation wards o worry about losing procedural and clinical competence and job uncertainty o fear for their own health and well-being due to caring for large numbers of covid-19 patients o increase in overall working hours due to shortage of staff o long time self-isolation periods away from their families and colleagues o decrease in the social interactions between families and colleagues o loss of autonomy • change the assessment method of competencies • provide supplementary teaching programs for residents missing out training programs • create social media chat group for communications • cancel the formal presentations and teaching programs to allow more time to spend with families • faculty stepping in to relieve residents of clinical workload • arrange weekly mindfulness sessions • availability of 24-h hospital psychologist • clear communication by program leadership regarding continuation of training and implications on job prospects sasangohar f, et al. (2020)(31) to describe lessons learned from a high-volume intensive care unit where the frontline hcps work, about burnout and fatigue during the covid-19 pandemic. • frontline hcps emotionally breaking down, due to the added pressure to choose between family responsibilities and their inner sense of duty toward patients. • it was seen support from medical leadership, public and private acknowledgments, community support (food sent to care units), music therapy, counseling services, chaplain services, and accommodations in work schedules. • organizational adaptations: allocation of more resources (float nurses, physicians, patient care assistants, and new equipment) • new protocols were published in response to the pandemic which were perceived as complex and premature. • policy overload coupled with mismatching policy from different levels or sources • each subspecialty follows guidelines provided by their respective professional societies for various procedures. • new policies were developed by the hospital. • social distancing and quarantine protocols resulted in unprecedented overall societal stress and anxiety. • job insecurity and uncertainty about future occupational stability increased for some specialists like some private anesthesia groups due to canceling and delay in routine elective surgeries. • organizational adaptation: o rapidly assembled the incident command team. o responsiveness and constancy of leadership–employee communication o adaptation of human resources policies to employee needs. o using digital communication tools for remote work and intra institutional collaborative efforts. o communications between specialist and learning through popular social media platforms. o opportunity for innovations and adoption of alternative care delivery methods like telemedicine and virtual icus. • develop guidelines to increase teamwork between different specialists and decrease confusion and frustration. • support increased demand for disinfectants, cleaning supplies, ppe, and other medical equipment for health care and community use. • assess updated information about availability of testing kits and ppe for to reduce the anxiety associated with uncertainty, and reduce unproductive information seeking and emotional stress. • use daily rounds along with communication technologies to access reliable information sources. • provide structured training on large-scale disaster management and response. • improve innovation as well as provide technical oversight to ensure that new designs meet minimum safety requirements. • employ other well-trained resource of medical professionals in the form of internationally trained physicians, nurses, medical technicians, and other hcps. • provide wearable sensors for noninvasive monitoring of fatigue, stress, and sleep biomarkers for timely intervention. • use mobile health (mhealth) tools for facilitating the mental health self-management. • use simple methods such as breathing exercises, biofeedback, and mindfulness to reduce cute episodes of stress and anxiety. • use telehealth services to enable peer-support and occupational counseling. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2021; 9(1): e7 table 2: articles in the format of opinion, editorial, letter, or prospective author methods main findings recommendations sultana a, et al. (2020)(32) to describe challenges and evidence-based interventions for burnout among hcps during covid-19 pandemic. psychological stressors for burnout: • working hard during emergencies or stressful conditions • workload • sleep deprivation • depression • lack of resilience • poor self-management • inappropriate work schedule • inappropriate workflow management • poor communications skills • poor coping skill • unsafe workplace • lack of mental health services • increase potential burnout awareness: can reduce stigma towards mental health conditions and develop resiliency. • decrease the workload • improve work schedule • promote self-management • initiate mindfulness-based stress reduction • mental health promotion activities • provide mental health services • involve mental health experts in multidisciplinary covid-19 teams • hold group-based counseling or peer-support sessions • balance use of electronic health records • monitor healthy work conditions • address the risks of workload and workplace stress • deliver mental health services through digital platform • improve workflow management • enhance interoperability • arrange discussion and exchanging opinions • improve communication skills • provisos for adequate rest and exercise • organize workshops on coping skills • devise policies and practices • develop supportive work environment this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sharifi et al. 16 table 3: the summary of recommendations for preventing or reducing burnout among healthcare providers (hcps) of covid-19 wards personal characteristics mental health status digital technologies workplace conditions and organizational behavior the society • increase health literacy (happiness, exercise, drinking water, being joyful, and having a good sleep) • include periods of rest and relaxation in shift program and schedules • provide restroom and possibility of taking a shower in the workplace • mandatory time away from work for spending with family, friends, hobbies, and rest • social support within the family • interaction with family members and loved ones • support family-related issues especially in married women (e.g. helping with childcare, transportation, temporary housing, and wages) • provide mental health services • provide counseling and support systems • involve mental health experts in multidisciplinary covid-19 teams • use consultation liaisons • promote mental health • promote resiliency • promote self-management • start mindfulness-based stress control activities • teach physical, mental, and emotional self-cares • improve relaxation skill • arrange stress management programs • use methods focused on mindfulness, stress management and small group discussion • provide cognitive behavioral therapy, yoga, tai chi, grief counseling, and music and art therapy • provide writing workshops through mental health services • provide mental health services and increase the empowerment of hcps through it • balance use of electronic health records • talk about concerns with colleagues and friends through web-based social media • use digital communication and social media platforms • use it for training • use it for sharing information • use it for immediate access to valid and up to date information • use it for virtual support groups such as book club, journal club, or coffee talk, virtual dinner, and happy hours • use telehealth services to enable peer-support and occupational counseling. • use it in the format of telemedicine and virtual icus • provide wearable sensors for noninvasive monitoring of fatigue, stress, and sleep biomarkers for timely intervention. • use it as mobile health tools (mhealth) • promote work culture • relieve workplace stressors • develop healthier and supportive work environment • give back autonomy, competence, and relatedness to physicians • improve workflow management • organize services with an emphasis on reducing workload (improve work schedule, reduce working hours, schedule breaks, floating work schedule, limit work hours) • improve communication skills • hold workshops on coping skills • arrange discussion meetings • increase interoperability • brainstorming around ways to change workplace and workload • increase shared decision making • provide the opportunity for having adequate rest and exercise • increase teamwork and job control • develop policies and methods to reduce burnout • support an infrastructure that allows hcps to work from home • provide cross-sectoral and inter-organizational collaboration to share information, resources, support • use strategic distribution of human resources • increase the number of human resources by hiring more hcps • employ foreign hcps • decrease clinicians from nonclinical tasks and medical notes • daily screening of vital signs, possible symptoms of infection, and signs of burnout • develop clear and updated guidelines and protocols for different situations • develop practical training about protective interventions • provide essential resources adequately (ppe, beds, medicines, ventilators) • provide social support • increase social interactions • decrease social violence this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2021; 9(1): e7 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flow diagram of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e27 or i g i n a l re s e a rc h efficacy of sumatriptan/placebo versus sumatriptan/propofol combination in acute migraine; a randomized clinical trial reza farahmand rad1, akram zolfaghari sadrabad1, mohammadali jafari2, marziyeh ghilian3∗ 1. clinical research development center, imam reza hospital, kermanshah university of medical sciences, kermanshah, iran. 2. emergency department, shahid sadoughi hospital, shahid sadoughi university of medical sciences, yazd, iran. 3. emergency department, mehriz fatemeh zahra hospital, shahid sadoughi university of medical sciences, yazd, iran. received: february 2022; accepted: march 2022; published online: 14 april 2022 abstract: introduction: migraine headaches can cause severe pain for patients and lead them to multiple visits to the emergency department (ed). this study aimed to evaluate the efficacy of propofol + sumatriptan combination in comparison with sumatriptan alone in the management of acute migraine headaches. methods: this tripleblind clinical trial involved patients who referred to two emergency departments with acute migraine headaches. patients were randomly assigned to control (sumatriptan and placebo) or intervention (propofol and sumatriptan) groups for comparison of the efficacy and side effects of treatment. results: in this study, 60 patients were included whose mean age was 31±8.8 years, and headaches were more common among women. after 30 and 60 minutes from the beginning of treatment, the mean pain score reduction in the intervention group was significantly greater than that in the control group (p=0.012, p=0.024). in addition, the rate of chest tightness in the control group was significantly higher than the intervention group. the absolute risk reduction of adverse events (chest tightness, bradycardia, hypotension, and etc.), in patients with acute migraine headache taking propofol and sumatriptan treatment, was 32.18% (95% ci: 8.02 – 56.35). conclusion: this study supports the use of propofol for treatment of acute migraine headaches and shows that combining sumatriptan with propofol is more effective in relieving migraine headaches and the associated symptoms than using sumatriptan alone. however, more studies with longer follow-ups are still needed. keywords: migraine disorders; headache; sumatriptan; propofol; pain management cite this article as: farahmand rad r, zolfaghari sadrabad a, jafari m, ghilian m. efficacy of sumatriptan/placebo versus sumatriptan/propofol combination in acute migraine; a randomized clinical trial. arch acad emerg med. 2022; 10(1): e27. https://doi.org/10.22037/aaem.v10i1.1510. 1. introduction there are more than 1.2 million emergency department visits for migraine headaches each year in the united states (1, 2); this disease is more common in women than in men (3). migraine is a chronic multifaceted disease that manifests as a one-sided, throbbing headache, nausea, vomiting, photophobia, and phonophobia (4). diagnostic criteria include headaches lasting at least 4 hours for at least 15 days ∗corresponding author: marziyeh ghilian; emergency medicine department, mehriz fatemeh zahra hospital, central administration, bahonar sq., yazd, iran. postal code: 8916978477, email: marziehghilian@yahoo.com, tel: +989134545004, fax number: +98 35 38282682, orcid: http://orcid.org/00000002-4716-6257. of the month, according to the international classification of headache disorders (5). although the international headache society (ihs) recommended acetaminophen, nsaids, triptans, and steroids for migraine headaches (6), none of these have been found to fully relieve migraine pain or lead to the desired clinical results (7). there are many migraine treatments available, but side effects and contraindications are two issues that we constantly deal with. interestingly, it seems that combinations of drugs can be effective for treating migraines (8). serotonin receptors play an important role in the pathogenesis of migraine headaches. the most important challenges in using sumatriptan are its side effects and limitations. since it is an effective and selective agonist for the vascular 5hydroxytryptamine receptor subtype, it is relied upon to treat this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. farahmand rad et al. 2 migraine attacks (9). in migraine, sumatriptan reduces some clinically important symptoms in two ways: first, it facilitates blood vessel contraction in certain parts of the brain as a 5ht 1b vascular receptor agonist; and second, it limits the breakdown of vasoactive neuropeptides. propofol also affects gamma-aminobutyric acid (gaba) receptors, preventing pain signals from reaching these receptors and significantly reducing pain scores in migraine patients (10). propofol reduces migraine pain by acting on gaba receptors (11), and this mechanism may be suitable for combination therapy (12). studies performed as clinical trials are few and the amount of propofol used varies widely, from a fixed amount based on weight to a constant amount of bolus. in general, propofol reduces pain and reduces headache recurrence, but some studies have shown that pain scores do not differ significantly between groups despite propofol being more effective than placebo (13). the present study’s purpose was to compare the efficacy and adverse effects of sumatriptan + propofol combination with sumatriptan alone for controlling acute migraine headaches in patients who referred to the emergency department (ed). 2. methods 2.1. study design and setting this triple-blind randomized clinical trial with a parallel design was performed in the emergency departments of shahid sadoughi and shahid rahnemoun hospitals, affiliated to yazd university of medical sciences, yazd, iran, during one year. using a table of random numbers, the participants were randomly allocated to sumatriptan + propofol or sumatriptan and placebo groups and the efficacy and side effects of treatment were compared between two groups. all the participants gave their informed consent to enter the study. this study was approved by the ethics committee of yazd university of medical sciences under the code ir.ssu.medicine.rec.1393.81 and was registered in the iranian registry of clinical trials under the code irct2015050422089n1. 2.2. participants the study population included patients with an acute attack of migraine headache who either had a migraine headache previously diagnosed by a neurologist or met the migraine headache criteria, based on the international headache association (ihs) definition, and were between 18 and 45 years old. cases with diagnosis of acute attack of non-migraine headache, refusal to participate in the study, pregnancy and lactation, cardiovascular diseases, drug addiction, diastolic blood pressure above 105 mmhg, cerebrovascular diseases, receiving ergotamine 24 hours before visiting the ed, egg allergies, ocular migraine, vestibular dysfunction, and hemiplegia were excluded. 2.3. intervention after allocation of eligible patients to case or control groups, all patients underwent cardiac monitoring and pulse oximetry and non-invasive measurement of blood pressure. intravenous (iv ) route was established for each case with angiocatheter gage 20. pain intensity was measured for all patients, by an emergency medicine specialist using a visual analog scale (vas), on arrival to ed. sumatriptan (6 mg in 0.5 ml) was injected subcutaneously (sc) and propofol (0.5 mg per kg body weight) was administered as a slow infusion for 1 hour. propofol and placebo were administered using a microset containing 100 ml of normal saline coated with an aluminum coating; to prevent the pain caused by propofol injection and to maintain study blindness, both drugs were administered to all the participants with 1 ml of 2% lidocaine via angiocath. all the injection procedures were performed by a nursing expert in the presence of an emergency medicine specialist. pain was measured by an emergency medicine specialist every 30 minutes for up to one hour after administration of the drug in each group. all the patients were evaluated for recurrence and side effects of medications 2 hours after receiving the drug. during the injection procedures, the patients were examined for any side effects and the drug was discontinued if any complication occurred. the final evaluation was performed one hour after the drug injection. the satisfaction of all the drug recipients was recorded. after one hour, if the patient’s pain reduction was less than 4 points, the response to medication was recorded as incomplete and ketorolac or opium was injected as rescue pain reliever for these patients. 2.4. outcome success rate of pain management and the rate of complication were the primary measured outcomes of study. to measure the pain severity, visual analogue scale (vas) was used. nausea, chest tightness, chest pain, neck and throat pain, ear discomfort, dysphagia, muscle weakness, warmth, paresthesia, cramps and burning, toothache, dizziness, meningitis, injection site pain, hypertension (blood pressure≥140/90 mmhg) and hypotension (systolic blood pressure<90 mmhg), and in rare cases, sudden death and mi were considered as the most probable side effects of sumatriptan (14-17). probable side effects of propofol were considered to be respiratory depression (respiratory rate <12), apnea (apnea is defined as a respiratory pause longer than 20 seconds), hypoxemia (o2 saturation below 90%), hypotension, bradycardia (heart rate <60 beat/min, myoclonus), pain during injection (18-22). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e27 figure 1: receiver operating characteristic (roc) curve of alveolar arterial gradient (best cut-off = 0.28; area under the curve (auc) = 0.602) and respiratory index (best cut-off = 0.28; auc = 0.522) in predicting the mortality of covid-19 cases. table 1: comparing the baseline characteristics of studied cases between intervention (sumatriptan and propofol) and control (sumatriptan and placebo) groups variable intervention (n=29) control (n=30) p age (year) 32.3 ± 9.5 29.7 ±8.1 0.26 gender male 9 (31.0) 7 (23.3) 0.56 female 20 (69.0) 23 (76.7) headache duration (hour) 5.1 ± 5.7 4.8 ±5.5 0.89 presenting pain score# 9.1 ± 0.9 8.9 ± 0.7 0.27 positive family history* 18 (62.1) 17 (56.7) 0.42 migraine type common 28 (96.5) 26 (86.7) 0.61 classic 1 (3.5) 4 (13.3) presenting symptoms photophobia 28 (96.6) 25 (83.3) 0.19 nausea 24 (82.8) 26 (86.7) 0.73 vomiting 12 (41.4) 18 (60.0) 0.19 phonophobia 5 (17.2) 7 (23.3) 0.75 data are presented as mean ± standard deviation or number (%). #: based on visual analogue scale. *: family history of migraine headache. 2.5. blinding in this study, blinding was performed at the following three levels: patients, researcher, and data processor. the drugs were pre-prepared by the study’s lead researcher and administered based on the kind of the group they belonged to. the specialist who recorded the severity of the pain, did not know the type of drug received. the data analyzer was unaware of the type of drug given to each group. 2.6. statistical analysis the sample size was determined to be 60 people, 30 people for each group, considering a significance level of 5%, a test power of 80%, a standard deviation of 1.3 for pain score, and with one unit difference between the mean pain score in the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. farahmand rad et al. 4 table 2: comparing symptom relief and adverse outcomes of treatments between intervention (sumatriptan and propofol) and control (sumatriptan and placebo) groups variable intervention (n=29) control (n=30) p pain relief# 30 minutes 4.6 ± 2.9 6.9 ± 1.8 0.024 1 hour 2.2 ± 2.7 5.5 ± 2.6 0.012 other symptoms’ relief photophobia 24 (82.8) 8 (26.7) 0.001 nausea 22 (75.9) 14 (46.7) 0.033 vomiting 9 (31.2) 5 (16.7) 0.232 phonophobia 3 (10.3) 1 (3.3) 0.353 ondansetron requirement number (%) 7 (24.1) 24 (80.1) 0.001 recurrence of symptom number (%) 10 (34.5) 6 (20.0) 0.254 adverse outcomes chest tightness 0 (0.0) 20 (66.7) 0.001 bradycardia and hypotension 7 (24.1) 0 (0.0) 0.05 other adverse effects 3 (10.3) 0 (0.0) 0.49 data are presented as mean ± standard deviation or number (%). #: based on visual analogue scale. two groups (23). the analyses were performed using spss version 15 (spss inc., chicago, il, usa). chi-square test was used to analyze the baseline nominal results. anova test was also performed for comparing age and time interval between the onset of headache and referral to the emergency department between the two groups. comparison of the effects of the drugs in the two groups on reducing pain (every 30 minutes after the treatment) was performed using the paired couple test. values of p <0.05 were considered as statistically significant differences. 3. results 3.1. baseline characteristics of studied cases in this study, 109 patients with headache complaints were evaluated during a one-year period. finally, 68 patients who met the inclusion criteria were enrolled in the study. nine patients were excluded after enrolment (eight due to lack of cooperation in providing the necessary information during performing the intervention, and one due to the decreased oxygen saturation to less than 80% after drug administration in the intervention group). therefore, 29 and 30 patients were evaluated in the intervention group and the control group, respectively (figure 1). table 1 compares the baseline characteristics of studied cases between intervention and control groups. the mean age of the patients in the intervention and control groups was 29.5±32.3 and 29.7±8.1 years, respectively (p = 0.26). the two groups were similar regarding gender distribution (p = 0.56), duration of headache (p = 0.89), presenting pain score (p = 0.27), positive family history of migraine headache (p = 0.42), migraine type (p = 0.61), and type of presenting symptoms (p > 0.05). 3.2. response to treatment table 2 compares the rate of symptom relief and side effects between the groups. the mean reduction in pain score in the intervention group 30 minutes (4.6 ± 2.9 vs. 6.9 ± 1.8; p = 0.024) and 60 minutes (2.2 ± 2.7 vs. 5.5 ± 2.6; p = 0.012) after treatment was greater than the control group. the rate of recovery of other symptoms was higher in the intervention group but the difference in recovery rate was statistically significant only regarding photophobia (82.8% vs. 26.7 %; p = 0.001) and nausea (75.9% vs. 46.7%; p = 0.033). the number of the patients requiring anti-nausea injection was significantly less in the intervention group (24.1% vs. 24 80%; p = 0.001). 3.3. side effects of treatment feeling of chest tightness was significantly observed in the control group (66.7%), which disappeared after 15 minutes, but in the intervention group, this complication was not reported (p=0.001). however, hypotension and bradycardia occurred significantly more in the intervention group compared to the control group (p = 0.05). in addition, weakness, drowsiness, and dizziness were seen in almost all the patients included in the intervention group, all of which resolved after drug administration and did not differ significantly from the control group. the absolute risk reduction of adverse events (chest tightness, bradycardia, hypotension, and etc.), in patients with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e27 acute migraine headache taking propofol and sumatriptan treatment, was 32.18% (95% ci: 8.02 – 56.35). 4. discussion the results of this study indicated a significantly greater improvement in symptoms associated with migraine headache as well as in pain score in the intervention group compared to the control group. these results suggest that the combination of propofol and sumatriptan results in a synergistic effect on controlling migraines, and that the side effects of sumatriptan like chest tightness, have reduced following the administration of a lower dose of the drug. in addition, this drug combination caused no new side effects for the patients in the intervention group. krusz et al. (24) examined the role of intravenous propofol in treatment of migraine headaches and showed that the mean reduction in headache severity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment with an average dose of 110 mg bolus. however, in krusz’s study, 86% of the patients had either nausea or vomiting at the time of propofol administration, or had both of them, which spontaneously resolved after the administration with no medication, possibly within 3 to 5 minutes due to bolus administration (24). in contrast, in our study, the patients did not experience any symptoms of nausea or vomiting due to the slow infusion. they have also stated that propofol, does not cause hemodynamic instability in patients receiving it, which may be due to the fact that the prescribed dose is less than the dose prescribed for anesthesia. in the present study, the patients in the intervention group experienced no hemodynamic instability, which could be due to a lower dose than the sedative dose and slow infusion of the drug. however, two patients in krusz’s study and one patient in the present study were excluded due to the decreased oxygen saturation. in krusz’s study, three recurrences were reported on the day after performing the treatment (24). in that study, recurrence of headache was reported after 72 hours in both groups, which was higher in the group receiving sumatriptan and placebo. this difference in recurrence rate may be due to administrating the drug via slow infusion and concomitant use of sumatriptan, which have led to a longer effect of the drug. in a study by soleimanpour (25), who compared the effects of propofol with dexamethasone on migraine, it was found that propofol could reduce pain more rapidly (within 10 minutes), while the pain relief in the dexamethasone group reached the equivalent of propofol after 20 minutes. also, patients receiving propofol showed fewer side effects compared to the controls and recurrence of refractory migraine has also reduced (25). in the present study, the rate of pain score reduction in the intervention group was similarly higher than the control group. in a double-blind clinical trial conducted by robert et al. (26), propofol was not superior to placebo in the early relief of headache; however, propofol was superior to placebo in reducing the severity of headache, which differed from the results obtained in this study. in robert’s study, intralipid was used as a placebo. in addition, no other drug has been used with propofol (26). in most cases, several analgesics were used to treat migraine headaches, especially refractory and high-intensity headaches. it is also true that intralipid is not known to be effective on treating migraines, but it contains some substances such as soybean oil, egg lectin, and glycerol, which is like an emulsion used as a basis for propofol (27). in addition, each of these substances can exacerbate migraine headaches, and there also are many challenges to propofol emulsions (28). in a study by mitra et al. (29), which was an open-label, randomized controlled pilot trial, they compared the procedural dose of propofol (1 mg/kg body weight) with the standard treatment chosen by the physician to control migraine headaches. accordingly, the study reported that propofol administration finally resulted in faster pain relief and shorter discharge times in patients with migraine headaches (29). in our study, pain reduction was similarly greater in the intervention group. furthermore, in mitra’s study, similar to the present study, only one patient experienced a decrease in saturation during propofol administration, which improved with oxygen uptake and no other side effects were reported. on the other hand, in that study, the procedural dose of propofol was used as a bolus injection and the maximum time to achieve optimal consciousness was 5 hours (29), but in the present study, none of the patients included in the intervention group entered the anesthesia phase due to the use of doses less than sedatives, concomitant use with other analgesics, and slow infusions. clinical practice guidelines vary for migraines. it is possible that the discrepancies observed when comparing with other instructions may be due to intravenous analgesia before reaching the emergency room. however, propofol, due to its clinical effect and immune profile in the adult population, appears to be a promising drug in the treatment of migraine in ed. based on the available evidence, propofol is a suitable treatment for pain relief and a last resort, especially for patients with refractory or incurable migraines, or in patients who have contraindications to the repeated use of first-line drugs, and it can be considered as a good alternative treatment. this study also showed that other drug combinations should be considered for the treatment of migraine because it seems that the drugs can improve each other’s effect and impose fewer side effects on patients by administrating lower doses of each one of these drugs, so they can benefit more from their enhanced therapeutic effect. finally, we suggest that the therapeutic effects of propofol and its effect on this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. farahmand rad et al. 6 the interval between the onsets of the next migraine attack be studied through long-term follow-up of patients. 5. limitations follow-up was performed by telephone and based on the patient’s statement, so there was no specific clinical criterion for recurrence. some patients may have used painkillers before the visit, which did not have a significant effect on the results due to the measurement of pain score, as an objective criterion, as well as the rate of reduction of this score after starting the treatment. after enrolment, eight participants were excluded because they failed to cooperate in providing the necessary information and another was excluded because their oxygen saturation was less than 80% following the intervention. 6. conclusion our results support propofol as a treatment for acute phase migraine and show that a combination of sumatriptan and propofol is more effective in relieving migraine headaches and their side effects compared to sumatriptan alone. 7. declarations 7.1. acknowledgments we are thankful to all of the participants for their cooperation. 7.2. authors’ contributions based on the recommendations of the international committee of medical journal editors, all authors passed four criteria for authorship contribution. 7.3. funding and supports there is no funding and support. 7.4. conflict of interest all authors confirm thet there is not any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. references 1. wu j, davis-ajami ml, kevin lu z. impact of depression on health and medical care utilization and expenses 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lieners c, baykan b. diet restriction in migraine, based on igg against foods: a clinical double-blind, randomised, cross-over trial. cephalalgia : an international journal of headache. 2010;30(7):829-37. 28. baker m, naguib m. propofol: the challenges of formulation. anesthesiology. 2005;103:860-76. 29. mitra b, roman c, mercier e, moloney j, yip g, khullar k, et al. propofol for migraine in the emergency department: a pilot randomised controlled trial. emerg med australas. 2020; 32(4):542-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e50 or i g i n a l re s e a rc h effect of collagen hydrolysate and fish oil on highsensitivity c-reactive protein and glucose homeostasis in patients with severe burn; a randomized clinical trial elham alipoor1, mohammad javad hosseinzadeh-attar2,3, shiva salehi2, mostafa dahmardehei4, mehdi yaseri5, mohammad reza emami2, mehdi hajian6, seyed mahdi rezayat7,8, shima jazayeri1,9∗ 1. department of nutrition, school of public health, iran university of medical sciences, tehran, iran. 2. department of clinical nutrition, school of nutritional sciences and dietetics, tehran university of medical sciences, tehran, iran. 3. cardiac primary prevention research center, cardiovascular diseases research institute, tehran university of medical sciences, tehran, iran. 4. department of plastic surgery, burn research center, motahari hospital, iran university of medical sciences, tehran, iran. 5. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 6. motahari hospital, iran university of medical sciences, tehran, iran. 7. department of pharmacology, school of medicine, tehran university of medical sciences, tehran, iran. 8. department of nanomedicine, school of advanced technologies in medicine, tehran university of medical sciences, tehran, iran. 9. research center for prevention of cardiovascular disease, institute of endocrinology and metabolism, iran university of medical sciences, tehran, iran. received: may 2021; accepted: june 2021; published online: 5 july 2021 abstract: introduction: collagen and omega-3 fatty acids (fas) are suggested to have anti-inflammatory, anti-oxidant, and insulin-sensitizing properties. the aim of this study was to investigate the effect of collagen hydrolysate and omega-3 fas on inflammation and insulin resistance in patients with major burns. methods: in this doubleblind randomized clinical trial, 66 patients with 20-45% burns were assigned to either of the three groups of collagen (40 gr/d), collagen (40 gr/d) plus fish oil (10 ml/d), or control. high-sensitivity c-reactive protein (hscrp), fasting blood glucose (fbg) and insulin concentrations, and homeostatic model assessment for insulin resistance (homa-ir) were assessed at baseline, as well as end of weeks two and three. results: based on posthoc analyses, hs-crp levels were significantly lower in the collagen (p=0.026) and collagen+omega-3 (p=0.044) groups compared to the control group, at week three. however, preto post(week three) changes of hs-crp were significantly higher only in the collagen+omega-3 group compared to the control group (173.2 vs. 103.7 mg/l, p=0.024). after three weeks of the intervention, insulin (11.3 and 11.9 vs. 22.8 µiu/ml) and homa-ir (2.9 and 2.8 vs. 7.9) values seemed to be clinically, but not statistically, lower in both intervention groups compared to the control group. preto post(week three) values of fbg decreased significantly in the collagen (p=0.002) and collagen+omega-3 (p=0.036) groups. insulin (p=0.008) and homa-ir (p=0.001) decreased significantly only in the collagen+omega-3 group at week three compared to the baseline. conclusion: supplementation with collagen hydrolysate and omega-3 fas can improve hs-crp concentration and probably insulin resistance in patients with severe burns. omega-3 fas had additional effects on modulating inflammation. larger clinical trials are needed to confirm the current findings especially in terms of glucose homeostasis. keywords: burns; collagen; inflammation; insulin resistance; fatty acids, omega-3 cite this article as: alipoor e, hosseinzadeh-attar m j, salehi s, dahmardehei m, yaseri m, emami m r, hajian m, rezayat s m, jazayeri s. effect of collagen hydrolysate and fish oil on high-sensitivity c-reactive protein and glucose homeostasis in patients with severe burn; a randomized clinical trial. arch acad emerg med. 2021; 9(1): e50. https://doi.org/10.22037/aaem.v9i1.1289. ∗corresponding author: shima jazayeri; department of nutrition, school of public health, iran university of medical sciences, shahid hemmat highthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. alipoor et al. 2 1. introduction major burns are recognized among the most severe physiologic stresses, which are accompanied with a specific metabolic response (1). burns are among the most prevalent types of injuries (2), which impose high costs on the healthcare systems proportional to the severity of the condition (3). despite significant reduction in post-burn mortality over the recent decades, morbidities are still a serious clinical challenge (4). hypermetabolism is a pivotal pathophysiologic response in burns (1, 4), which is associated with other profound disorders including inflammation, oxidative stress, and insulin resistance (4-6). inflammatory mediators are major players in hypermetabolic response, which increase considerably after burn injury and may last for weeks depending on the severity of injury (5). glucose metabolism is remarkably altered in thermal injuries and insulin resistance may be prolonged following burns (1, 4). endoplasmic stress in muscles, skin, and adipose tissue are correlated with structural changes in insulin receptors and mitochondrial dysfunction, which in turn lead to glucose intolerance and disturbed lipid metabolism (7, 8). catecholamines and stress hormones, especially cortisol, are other main mediators of the hypercatabolic response (1, 4), which increase glucose flow through induction of proteolysis, lipolysis, and gluconeogenesis, and also trigger systemic inflammation (1). high glucose production is also largely associated with burn wounds to support the glucose demand of cells during anaerobic metabolism (9, 10). the main aim of such systemic endocrine and metabolic responses in metabolic stresses are to support normal homeostasis and prevent complications such as infection. however, certain aspects of this response are maladaptive and in the case of glucose intolerance it may lead to delayed wound healing, high risk of sepsis, organ failure and mortality (8, 11). prolonged inflammation may also delay wound healing (12). thus, effective interventions are required to modulate post-burn metabolic disorders. nutritional therapy is necessary in patients with major burns to provide metabolic needs as well as to modulate hypermetabolism and its consequences (13). providing adequate amounts of high-quality proteins is of great importance due to heavy losses of protein, increased gluconeogenesis, and tissue repair (14). collagen is a protein source, which has received an increasing attention recently. the beneficial effects of collagen have been suggested on wound healing and way, tehran, iran. postal code: 1449614535. tel: +982186704805, fax: +982188622707, e-mails: sh_jaz@yahoo.com, jazayeri.sh@iums.ac.ir, orcid: https://orcid.org/0000-0002-6013-4209. tissue repair in burns (15), diabetes (16) and aging (17). it has been suggested that collagen also has anti-inflammatory, anti-oxidant, and anti-diabetic properties (18-20) in excisional wounds and other experimental models, which have not yet been investigated in burns. omega-3 fatty acids (fas) are other important nutrients with anti-inflammatory properties, which were reported to be advantageous in reduction of infection, sepsis, and septic shock (21, 22), as well as decreasing hospital (21) and intensive care unit (23) stay in burns. studies in burns have mainly investigated the antiinflammatory effects of omega-3 fas in combination with other nutrients as enteral or parenteral formulas (21, 23, 24) or from plant sources (25), and thus the reported results are conflicting. omega-3 fas could also improve insulin resistance (26), which has been limitedly investigated in burns. thus, considering the importance of alleviating post-burn pathophysiological disorders with appropriate intervention and given the promising effects reported for collagen and omega-3 fas in non-burn studies, this trial aimed to assess the effect of collagen hydrolysate and omega-3 fas on inflammation and glucose homeostasis in patients with major burns. 2. methods 2.1. study design and participants the current study was a double-blind parallel-design randomized controlled clinical trial (rct) in 66 patients with major burns. the inclusion criteria were 20-45% total body surface area (tbsa) burn, 2nd (deep partial thickness) or 3rd (full thickness) burn degrees and age 18-60 years. patients with history of diabetes mellitus, organ failure, cancer, immune disorders, and allergy or intolerance of protein as well as , body mass index (bmi) < 18.5 kg/m2, pregnant, lactating and post-menopausal women, those who needed intensive medical care, enteral or parenteral nutritional support, or those who were reluctant to participate in the study were excluded. all patients received standard medical and surgical care during the study period. the study protocol has been approved by the institutional ethics committee of the iran university of medical sciences (ethics code: ir.iums.rec.1397.442) and registered on iranian registry of clinical trials (irct: irct20090901002394n42). all patients gave a written informed consent in the beginning of the study. 2.2. procedure eligible patients were randomly assigned to either of the three groups of control (n=22), collagen (n=22), or collagen plus fish oil (n=22) based on stratified permuted block randomization using a randomization sequence generated by a random allocation software, with random block sizes of 3 and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e50 6. patients were stratified based on tbsa < or > 30%. patients in the collagen group received a drink containing 40 gr hydrolyzed collagen (rousselot, france) and 10 ml sunflower oil per day, in two divided doses, for three weeks. the combination therapy group received the same amount of collagen in addition to 10 ml/d fish oil (striver, india), containing 3 gr omega-3 fas, for three weeks. the control group received a carbohydrate drink with 10 ml/d sunflower oil, similar in taste and color. the drinks were prepared and coded by an independent colleague unaware of the study design. the toronto formula was used to determine the calorie need of each patient, individually. the protein need was considered 20-25% of total calorie need. 2.3. assessments all measurements were performed at baseline, end of weeks two and three. blood samples were obtained after 8-10 hours of fasting and the sera were kept at -80 °c after centrifugation. fasting blood glucose (fbg) was determined using enzymatic method (pars azmoon inc., iran). fasting insulin levels were measured using enzyme-linked immunosorbent assay (elisa) kit (diametra, italy). homa-ir was calculated using the relevant formula: fbg (mg/dl) × fasting insulin (µu/ml) / 405. hs-crp concentration was measured based on immunoturbidimetry assay (roche diagnostics, germany). body weight and height were measured using a scale with height rod (seca, germany). a 24-h dietary recall was obtained from all patients by a trained researcher at baseline, and weeks two and three. dietary reported intakes were analyzed using nutritionist iv software (n squared computing, san bruno, ca, usa). 2.4. statistical analysis based on the relevant formula for rct studies a sample size of 22 deemed to be adequate to have a power of 80% to detect 30 mg/l difference in hs-crp levels, when post intervention standard deviation (sd) was assumed to be 33, with a type i error of 0.05 and a drop-out rate of about 15%. the kolmogorov–smirnov test was used to assess the normal distribution of variables. per-protocol analyses were performed to assess differences in the baseline values as well as preto postchanges of the outcomes using chi-square, analysis of variance (anova), and kruskal-wallis tests, where appropriate. the effects of the intervention at the end of weeks two and three were investigated using analysis of covariance (ancova) adjusted for baseline values. post-hoc analyses were performed to assess the statistical differences between each two groups. repeated measure and friedman tests were applied for within group comparisons (preto postchanges) in each study group. all analyses were performed using spss software (ibm spss statistics for windows, version 26.0. armonk, ny: ibm corp.). p-value < 0.05 was considered to be statistically significant. 3. results 3.1. baseline characteristics in the current study, 66 patients were randomly assigned to three groups to receive either of the collagen, collagen+omega3 or placebo. three patients, one in each group, did not receive the allocation due to withdrawal or lack of baseline assessments. three patients in the control (one death, one discharge against medical advice from hospital, one transfer to another hospital), one in the collagen (need for intensive care), and two in the collagen+omega3 (need for intensive care) were excluded from the study. finally, 18 patients in the control, 20 in the collagen, and 19 in the collagen+omega3 completed the study. baseline characteristics of the study population have been presented in table 1. there were no significant differences in age, sex, tbsa, burn depth, and burn etiology between the three study groups. 3.2. hs-crp concentration there was no baseline difference in circulating hs-crp between the study groups. following three weeks of the intervention intervention, hs-crp concentration was significantly different between the study groups (p=0.018) (table 2). post-hoc analyses showed considerably lower hs-crp in the collagen (p=0.026) and collagen+omega-3 (p=0.044) groups compared to the control group. additionally, preto post(week three) changes of hs-crp were significantly different between the three study groups (p=0.027). posthoc analysis showed significantly higher decrease of hs-crp only in patients receiving collagen+omega-3, but not collagen alone, compared to the control group (173.2 vs. 103.7 mg/l, p=0.024) (table 2, figure 1). figure 1: changes in high-sensitivity c-reactive protein (mg/l) concentration throughout the study period. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. alipoor et al. 4 3.3. glucose homeostasis there were no statistically significant differences in the baseline or post-intervention values of fbg, insulin, and homair between the three study groups. there was a significant decrease in fbg levels within the collagen (p=0.002) and collagen+omega-3 (p=0.036) groups at the end of week three compared to the baseline. additionally, preto post(week three) changes of insulin (p=0.008) and homa-ir (p=0.001) were statistically significant only within the collagen+omega3 group. post-intervention values of insulin (11.3 and 11.9 vs. 22.8 µiu/ml) and homa-ir (2.9 and 2.8 vs. 7.9) seemed to be clinically, but not statistically, lower in both intervention groups compared to the control group (table 3, figure 2). in the collagen+omega-3 group, 88.9% of patients had a decreasing trend in homa-ir from baseline to the end of the study, while 73.7% of patients in the collagen and 58.8% in the control group had such a trend, and the rest of patients in each group had increased insulin resistance throughout the study. 3.4. other variables there was no significant difference in body weight at the end of the intervention between the control, collagen, and combination therapy groups (75.8±19, 74.7±12.6, and 73.4±16 kg, respectively, p=0.519). all the study groups had significant improvement in total energy and protein intake compared to their baseline values (all p<0.01). there were no significant differences in energy (2520.1±576.8 vs. 2359.8±605.6 vs. 2449±618.5 kcal/d, p=0.508) or amount of protein intake (121±18.3 vs. 129.7±23.5 vs. 130.6±28.3 gr/d, p=0.545) at the end of the study between control, collagen, and collagen+omega-3 groups, respectively. the percentage of protein intake from energy was significantly higher in the collagen group compared to the control group at weeks two and three, as well as changes in this nutrient on week three compared to baseline (p=0.04, p=0.019, p=0.048, respecfigure 2: changes in homeostatic model assessment for insulin resistance values throughout the study period. tively). these differences have been considered in statistical analyses and did not affect the significance of the findings. there were no significant differences in baseline or postintervention dietary intakes of carbohydrates, total fats, and micronutrients between the study groups (data not shown). 4. discussion the results of the current trial showed lower hs-crp levels in patients receiving collagen alone or in combination with omega-3 fas compared to the control group following three weeks of supplementation; however, the preto postdecrease of hs-crp was significantly higher only in the collagen+omega-3 fas group compared with the control group. no statistically significant difference was observed in glucose homeostasis between the study groups following the supplementation. however, insulin and homa-ir were lower in both intervention groups compared to the control group at week three, which seems to be of clinical importance. the lack of statistically significant differences in secondary outcomes, including insulin and homa-ir, between the study groups, might be partly due to the low power of the study; as the sample size has been calculated based on hscrp levels as the primary outcome. the reductions in fbg, insulin, and homa-ir were statistically significant within the collagen+omega-3 group at week three compared to the baseline. inflammatory markers such as hs-crp, as well as glucose and insulin levels are recognized to be predictors of survival in burns exceeding 30% tbsa (27). hs-crp levels are increased systematically and also locally at tissue levels of the burn site and may be elevated for days and months after the burn injury (12, 28). studies have shown impaired glucose homeostasis, high insulin levels, and insulin resistance for at least 4-5 weeks after burns (29). maladaptive responses after injury lead to complications and interfere with the healing process (8, 11, 12). thus, timely and effective interventions would be of special importance in burns to accelerate alleviation of the metabolic responses. no previous study was found investigating the effect of collagen on inflammation and glucose homeostasis in burns or other metabolic stresses. an rct showed the effect of three months of supplementation with 13 gr/d marine collagen on improvement of fbg, insulin, hemoglobin a1c, hscrp, free fas, and nitric oxide (no) in patients with type 2 diabetes compared to the control group (30). an experimental study in diabetic mice with full-thickness excisional wound showed significantly lower serum pro-inflammatory cytokines interleukin (il)-1β and il-8, higher serum antiinflammatory cytokine il-10, as well as better glucose tolerance and fasting glucose following 15 days of supplementation with marine collagen peptide mixture (30 and 45 gr/l) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e50 table 1: comparing the baseline characteristics of the patients between the three study groups variables control (n=18) collagen (n=20) collagen+omega-3 (n=19) p age (year) mean ± sd 37.3±12.4 33.2±9.6 34±11.4 0.488 a sex male 14 (77.8) 14 (70.0) 14 (73.7) 0.863 b female 4 (22.2) 6 (30.0) 5 (26.3) burn tbsa (%) mean ± sd 28.1±9.3 27.5±6.9 29.2±8.4 0.801 a burn depth 2nd degree (deep) 18 (100.0) 20 (100.0) 19 (100.0) 1.000 c 3rd degree 16 (88.9) 17 (85.0) 17 (89.5) > 0.9 c etiology flame 13 (72.2) 14 (70.0) 12 (63.2) scald 3 (16.7) 4 (20.0) 3 (15.8) 0.736 c alcohol & thinner 0 (0.0) 1 (5.0) 2 (10.5) electricity 2 (11.1) 1 (5.0) 2 (10.5) values presented as mean ± standard deviation (sd) or frequency (%); a: based on anova test; b: based on chi-square test; c: based on fisher’s exact test. tbsa: total body surface area. table 2: high-sensitivity c-reactive protein (hs-crp) concentrations in the three study groups before and after supplementation with collagen and omega-3 fatty acids hs-crp (mg/l) control (n=18) collagen (n=20) collagen + omega-3 (n=19) p baseline 170.9±110.9 164.2±76.2 185.2±83.6 0.746 a week-2 108±92.4 72.5±79.9 75±73.1 0.224 b week-3 50.4±66.4 17.6±34.1 21.2±30.1 0.018 b week-2 vs. baseline 62.9±95.6 93.2±85.5 110.3±86.5 0.273 a p (week-2 vs. baseline) c 0.065 <0.001 <0.001 week-3 vs. baseline 103.7±90.5 146.6±56.1 173.2±75.7 0.027 a p (week-3 vs. baseline) c 0.001 <0.001 <0.001 values are presented as mean± standard deviation (sd). a: based on anova test; b: based on ancova test adjusted for baseline; c: based on repeated measures. (19). a recent experimental study investigating the effect of eight weeks of marine collagen (100, 200, and 300 mg/kg) supplementation in high-fat fed mice showed decreased insulin concentration and improved homa-ir. collagen supplementation increased the hepatic expression of nuclear factor erythroid 2-related factor 2 (nrf2) and antioxidant enzymes, superoxide dismutase (sod) and glutathione peroxidase (gpx), and decreased nuclear factor kappa β (nfkβ)-regulated inflammatory enzymes and mediators such as cyclooxygenase-2 and il-6 (18). another experimental study showed no significant difference in glucose homeostasis but lower expression of il-6 and il-1β in adipocytes following 20 weeks of supplementation with fish collagen (4 g/kg/d) in mice fed a high-fat diet (31). a rat model of diabetes that received marine collagen (2.25, 4.5, and 9 g/kg/d for 4 weeks) indicated improved glucose metabolism and insulin resistance, as well as up-regulated glucose transporter type 4 (glut 4) in skeletal muscles, and peroxisome proliferator activated receptor-α (ppar-α) in the liver. there was a decrease in oxidative stress (higher sod, gpx, no, and lower malondialdehyde (mda)) and inflammation (lower tumor necrosis factor α, crp, interferon γ) in the intervention compared to the control group. most effects were observed in medium and high doses of the supplement but crp levels decreased even with low doses of collagen (20). collectively, the beneficial effects of collagen on inflammation and metabolic control might be due to its anti-inflammatory, anti-oxidant, and anti-diabetic properties, as well as the specific amino acid content of this protein. most available studies have used marine sources of collagen and some used large doses of the supplement; however, the current trial showed the beneficial effects of a bovine source of the protein as well. adding omega-3 fas to collagen was associated with clinical, but not statistical, improvement in insulin resistance and significant decrease of hs-crp levels compared to the control group throughout the study, which suggests the synergistic effects of collagen and omega-3 fas. the co-administration of these nutrients, as well as oral intake of omega-3 fas and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. alipoor et al. 6 table 3: glucose homeostasis in the three study groups before and after supplementation with collagen and omega-3 fas variables control (n=18) collagen (n=20) collagen+omega-3 (n=19) p fbg (mg/dl) baseline 114.9±27.5 108.5±18.9 114.7±49.2 0.545 a week-2 102.4±17 102.2±15.2 101.2±19.1 0.953 b week-3 102.8±23.8 95±13.5 93.6±12.2 0.227 b week-2 vs. baseline 12.6±35 6.6±17.6 13.5±46.2 0.539 a p (week-2 vs. baseline)c 0.091 0.991 0.768 week-3 vs. baseline 12.1±34.1 13.5±17.4 21.1±45.4 0.952 a p (week-3 vs. baseline)c 0.059 0.002 0.036 insulin (µiu/ml) baseline 21.1±26.1 17.7±24 22.6±18.9 0.365 a week-2 18.8±23.4 25.4±23.7 18.6±17.4 0.593 b week-3 22.8±45.6 11.3±11.2 11.9±13.4 0.388 b week-2 vs. baseline 3±34.7 -7.5±36 4±28.4 0.178 a p (week-2 vs. baseline)c 0.523 0.51 1 week-3 vs. baseline -1.1±54.6 7.1±24.2 10.3±25.8 0.283 a p (week-3 vs. baseline)c 0.523 0.51 0.008 homa-ir baseline 6.6±8.5 5.6±9.9 6.4±5.2 0.436 a week-2 5.1±7.0 6.4±6.2 5.1±5.7 0.798 b week-3 7.9±20.7 2.9±3.1 2.8±3.2 0.356 b week-2 vs. baseline 1.7±11.4 -0.7±12.8 1.3±8.2 0.156 a p (week-2 vs. baseline)c 0.381 0.51 1 week-3 vs. baseline -1.1±23.1 3±10.1 3.4±6.6 0.292 a p (week-3 vs. baseline)c 0.309 0.51 0.001 values presented as mean ± standard deviation (sd). a: based on kruskal-wallis test; b: based on ancova test adjusted for baseline; c: based on friedman test. fbg: fasting blood glucose; homa-ir: homeostatic model assessment for insulin resistance. the effect of these fats on insulin resistance were rarely investigated in burns so far. additionally, studies on burns have mostly investigated omega-3 fas in combination with other nutrients and nutraceuticals, as enteral or parenteral formulas. a double-blind rct investigating the effect of early enteral feeding enriched with omega-3 fas (3 gr/d) and glutamine (0.3 gr/kg/d) showed significant decline in crp levels 7 and 14 days after the injury compared with standard formula in patients with 30-50% tbsa burns (21). a doubleblind rct study has reported a significant decrease in hscrp following three weeks of supplementation with isolated soy protein (50 gr/d) alone or in combination with flaxseed oil (30 gr/d) compared to the control group in patients with 20-50% tbsa burn. no additional effect was observed for flaxseed oil on hs-crp levels in this study (25). an rct that evaluated the effect of a formula containing fish oil (20% of total fat), arginine (20% of total protein), and glutamine (10% of total protein) compared to standard formula showed no improvement in crp and immunologic biomarkers in patients with severe trauma or 30-60% tbsa burn (23). interestingly, a double-blind rct investigating the effects of a formula supplemented with fish oil (3.5 gr omega-3 fas/1000 kcal) and arginine (10 gr/1000 kcal) in patients with burns > 20% tbsa showed higher infection and crp levels in the intervention compared to the control group throughout the study (24). a clinical study in a mixed population with varying degrees of burns, 10-89% tbsa and 0-79% full thickness, age 3-76 years, and length of nutritional support of 7-61 days showed no significant differences in acute phase proteins, crp, and immunological markers with an enteral formula containing 50% fat from fish oil compared to the control formulas. there was an improving trend of glucose tolerance, indicated by lower need of exogenous insulin (32). the results of this study may be affected by the heterogeneity of the patients’ characteristics. discrepancies in the results of the mentioned studies might be due to differences in their dosage, duration, severity of condition, route of feeding, interactions with other nutrients and nutraceuticals, and the source of omega-3 fas. omega-3 fas alter cell membrane fluidity and increase prostaglandin, thromboxane, and leukotriene series with less inflammatory properties compared to eicosanoids derived from arachidonic acid, and decreases inflammatory cytokines (33), which, in turn, could ameliorate the catabolic response. part of the beneficial effects of omega-3 fas are conducted by the production of mediators known as “specialized proresolving mediators (spms)”. these mediators have a key and active role in altering the principal signs of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e50 resolution of inflammation (34, 35). experimental studies of transgenic models have shown the insulin-sensitizing, antisteatotic, and anti-inflammatory effects of spms (36, 37), but few clinical studies are available on the subject. 5. limitations this study had some limitations including the lack of oral glucose tolerance test, which could have made the results more precise. additionally, investigating other indicators of inflammation as well as the plausible mechanisms of the observed changes should be considered in future studies with larger sample sizes. part of the non-statistically important, although probably clinically significant, differences of postintervention glucose homeostasis parameters in this study might be due to the relatively low sample size for these secondary outcomes. 6. conclusion supplementation with collagen hydrolysate and omega-3 fas improved hs-crp concentration and insulin resistance in patients with major burns, although the latter did not reach statistical significance. omega-3 fas had additional effects on modulating inflammation. further large and welldesigned clinical trials are required to confirm the current findings, especially in terms of glucose homeostasis, in patients with major burns. 7. declarations 7.1. acknowledgments none. 7.2. funding and support this study has been supported by iran university of medical sciences grants 33869 and 12325, and tehran university of medical sciences grant 43535. 7.3. author contribution conceptualization and design, e.a., m.j.h.a., m.d., m.y., s.m.r. and sh.j.; methodology, e.a., m.j.h.a., m.y. and sh.j.; formal analysis, e.a. and m.y.; investigation, e.a., sh.s., m.r.e. and m.h.; data curation, e.a., sh.s., m.r.e., m.h. and m.y.; writing the original draft, e.a.; writing review and editing, e.a., m.j.h.a., m.d., m.y., s.m.r. and sh.j.; supervision, m.j.h.a., m.d., s.m.r. and sh.j.; funding acquisition, m.j.h.a. and sh.j. all authors have read and agreed on the published version of the manuscript. 7.4. conflict of interest none. references 1. atiyeh bs, gunn swa, dibo 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diet-induced obesity and associated disorders are prevented by natural bioactive type 1 fish collagen peptides (naticol®) treatment. j physiol biochem. 2018; 74 (4):647-54. 32. gottschlich mm, jenkins m, warden gd, et al. differential effects of three enteral dietary regimens on selected outcome variables in burn patients. journal of parenteral and enteral nutrition. 1990; 14 (3):225-36. 33. calder pc. omega-3 fatty acids and inflammatory processes. nutrients. 2010; 2 (3):355-74. 34. molfino a, amabile mi, monti m, muscaritoli m. omega-3 polyunsaturated fatty acids in critical illness: anti-inflammatory, proresolving, or both? oxidative medicine and cellular longevity. 2017; 2017 35. martindale rg, warren mm, mcclave sa. does the use of specialized proresolving molecules in critical care offer a more focused approach to controlling inflammation than that of fish oils? current opinion in clinical nutrition & metabolic care. 2016; 19 (2):151-54. 36. gonzález-périz a, horrillo r, ferre n, et al. obesityinduced insulin resistance and hepatic steatosis are alleviated by ω-3 fatty acids: a role for resolvins and protectins. the faseb journal. 2009; 23 (6):1946-57. 37. white pj, arita m, taguchi r, kang jx, marette a. transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat–fed mice. diabetes. 2010; 59 (12):3066-73. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e45 or i g i n a l re s e a rc h the effect of exercise-based pulmonary rehabilitation on quality of life in recovered covid-19 patients; a quasiexperimental study seyed mansoor rayegani1, rama bozorgmehr2, leila angooti oshnari3∗, amir hossein mahdi kaghazi4 1. physical medicine and rehabilitation research center, shahid beheshti university of medical sciences, tehran, iran. 2. clinical research development unit, shohada-e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. physical medicine and rehabilitation research center, occupational therapy department, shohada-e-tajrish hospital, shahid beheshti university of medical science, tehran, iran. 4. physical medicine and rehabilitation research center, shahid beheshti university of medical sciences, tehran, iran. received: march 2022; accepted: may 2022; published online: 8 june 2022 abstract: introduction: the coronavirus disease 2019 (covid-19) is associated with a variety of physical and emotional disorders, and subsequently lower quality of life (qol). this study aimed to investigate the effect of a 2-week exercise-based pulmonary rehabilitation on clinical characteristics and qol of severe covid-19 patients after discharge from intensive care unit (icu). methods: in this quasi-experimental study, eligible severe covid-19 cases, who had survived and were discharged from icu were selected using convenience sampling method. oxygen saturation ( spo2), pulse rate, dyspnea, and qol were evaluated and compared before and after two weeks of exercise-based pulmonary rehabilitation (pr). results: 35 cases with the mean age of 57.86 ± 11.73 (18-75) years were studied (51.4% female). the mean spo2 increased from 90.41 ± 3.97 to 95.11 ± 1.96% after two weeks of pulmonary rehabilitation (p<0.0001). in addition, the mean pulse rate (98.97±16.23 to 88.91±14.03 pulse/minute; p<0.001) and the mean dyspnea severity (5.6±1.97 to 3.45±1.97; p<0.0001) decreased after two weeks of intervention. besides, the mean total qol and its dimensions, including general health (p<0.0001), physical status (p<0.0001), emotional status (p = 0.036), and social function (p<0.0001) of patients, had significantly increased after intervention. conclusion: based on the findings of this study, it seems that two-week exercise-based pulmonary rehabilitation could be effective in increasing the spo2, decreasing dyspnea and pulse rate, and improving the qol of patients with severe covid-19 after discharge from icu. keywords: covid-19; exercise therapy; lung; rehabilitation; quality of life cite this article as: rayegani sm, bozorgmehr r, angooti oshnari l, mahdi kaghazi ah. the effect of exercise-based pulmonary rehabilitation on quality of life in recovered covid-19 patients; a quasi-experimental study. arch acad emerg med. 2022; 10(1): e45. https://doi.org/10.22037/aaem.v10i1.1569. 1. introduction the coronavirus disease 2019 (covid-19) appeared in wuhan, china in december 2019, and three months later, the world health organization declared it a pandemic. at that time, iran was ranked the third most-affected country in the world. patients diagnosed with covid-19 may ex∗corresponding author: leila angooti oshnari; occupational therapy unit, department of physical medicine and rehabilitation, shohada-e-tajrish hospital, shohada-e-tajrish hospital, tajrish sq., tehran, iran. postal code: 1989934148 email: leylaa1768@yahoo.com, tel: +989125046923, orcid: http://orcid.org/0000-0001-6059-5892. perience a wide range of clinical manifestations, which are categorized into no symptoms, mild, moderate, severe, and critical symptoms. fever, dry cough, sore throat, restlessness, muscle and joint pain, nasal congestion, sneezing and running nose, respiratory failure, general systemic dysfunction, and acute respiratory syndrome are some of the known signs and syndromes related to covid-19 (1-6). it proves that treatment and outcomes of covid-19 depend on the disease severity (4). outpatients diagnosed with covid-19 may experience symptoms for more than four weeks, which is called long covid-19 (7). fatigue, dyspnea, muscle pain, weakness, and psychological distress are the most common symptoms in patients with long covid-19 (6, 7). a vast range of physithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. rayegani et al. 2 cal and psychological disorders, along with decreased quality of life (qol), are associated with sars-cov-2 infection (4, 710). based on previous studies and guidelines, rehabilitation programs would be effective for patients diagnosed with covid19, especially in patients who were hospitalized (2, 5, 11, 12). all these programs, including aerobic exercises, strengthening, and stretching exercises of respiratory muscles may improve cardiorespiratory tolerance and physical function of patients, as well as their quality of life (13). in addition, respiratory exercises, such as diaphragmatic, bud lip, and resistance breathing will help in reducing active coughing in such patients (2, 14). this study aimed to investigate the effect of a 2-weeks exercise-based pulmonary rehabilitation on clinical characteristics and qol of severe covid-19 patients after discharge from intensive care unit (icu). 2. methods 2.1. study design and setting this quasi-experimental study with before-after design, was performed on severe covid-19 cases, who had survived and were discharged from intensive care unit of shohadae-tajrish hospital, tehran, iran, during 2021. o2 saturation ( spo2), pulse rate, dyspnea, and qol were evaluated and compared before and after two weeks of pulmonary rehabilitation (pr) in enrolled patients. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.retech.rec.1400.531) and also registered in iranian registry of clinical trials (irct20211201053238n1). written informed consent forms were signed to participate in the research. personal information was kept confidential and patients were given an identification code in the questionnaire form, instead of mentioning their name. 2.2. participants being aged between 18 and 75 years, recovered from severe covid-19, hospitalized to icu (between 3 to 18 weeks), satisfied to participate in the research, and referred to the department of physical medicine and rehabilitation by pulmonologist and intensive care specialist due to respiratory failure, as well as not receiving any pr before the study were among the inclusion criteria. patients who had problems with pulmonary massage, including active wounds, fractures and skin disorders in the chest area (15), a history of uncontrolled cardiovascular problems, chronic obstructive pulmonary disease (copd), renal, neurological, and cognitive problems, acute rheumatic diseases, hypertension, hemoptysis, psychology disorder, and cancer which lead to not being able to do exercises were excluded. 2.3. data gathering the data regarding demographic characteristics, spo2, pulse rate, dyspnea, and qol were collected for all patients before and after two weeks of pulmonary rehabilitation by trained occupational therapist in physical medicine and rehabilitation clinic. measurements of spo2 and pulse rate was done using pulse oximeter (choicemed made in china (with coefficient of variation (cv ): 0.01)). the level of dyspnea was calculated using valid and reliable modified borg scale, which is subjective and rated by the patient from one up to 10 (16). the qol was measured using sf-36 questionnaire, which has been proven reliable and valid for iranians by montazeri with intra class reliability and coefficients: <0.05 (17). generally, sf-36 questionnaire investigates the patient in 8 areas (physical status, physical role, body pain, emotional status, emotional role, social function status, fatigue, general health), and consists of eleven parts and 36 multiple choice questions. in this study, general qol and its’ 4 dimensions, including physical status (physical status, physical role, body pain, fatigue), emotional status (emotional status, emotional role), general health, and social function were evaluated. 2.4. intervention pr included training to stay in one of 5 sitting or standing comfortable positions and getting head and shoulders down and breathe in and blow out at first through the mouth and after that doing diaphragmatic breathing for 5 minutes to ease shortness of breath, getting lung massages (with cupping and vibratory techniques) (18) and doing 10 kinds of exercises. the exercises consisted of 3 respiratory exercises, including pursed lip in diaphragmatic, shoulder shrugging and rib breathing, 2 upper extremity exercises, reaching arms to the sky and elbows touch, and 5 lower limbs exercises, including hip hiking, knee abduction/adduction in crock lying, foot rocking in sitting, stepping, and squatting in standing position (18, 19) with 10 repeat, in two face to face sessions in the first week (sundays and tuesdays for 60 minutes) and the follow up during all the second week. all the enrolled patients were followed up for two weeks. 2.5. statistical analysis the study sample size was calculated as 35 based on two variables; spo2 and qol, with 95% confidence interval, power = 80%, and d=0.02 (19). after data gathering and coding, analysis of variances with wilcoxon and repeated measurement were used to analyze the data in 26-spss. spo2, dyspnea, and emotional status and social function of qol did not have normal distribution and the wilcoxon method was used instead of paired t-test. the findings were reported as mean ± standard deviation or frequency (%). p < 0.05 was considered as level of significance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e45 table 1: baseline characteristics of studied patients variable value gender female 18 (51.4) male 17 (48.6) start of disease to the initial assessment (days) 21-56 18 (51.4) 57-91 14 (40.0) 92-126 3 (8.6) marital status single 4 (11.4) married 22 (62.9) widowed/divorced 9 (25.7) education illiterate 4 (11.4) primary school 14 (40.0) high school 11 (31.4) university 6 (17.1) job housewife/none 23 (65.7) employed 12 (34.3) data are presented as frequency (%). 3. results 3.1. baseline characteristics of patients 35 cases with the mean age of 57.86 ± 11.73 (18-75) years were studied (51.4% female). the mean body mass index (bmi) of studied cases was 23.31 ± 3.36 kg/m2 and the mean time interval between the start of disease to the initial assessment in hospital was 56.01 ± 25.06 days. baseline characteristics of patients are presented in table 1. 3.2. outcomes of interventions the mean spo2 increased from 90.41 ± 3.97 to 95.11 ± 1.96% after two weeks of pulmonary rehabilitation (p<0.0001). in addition, the mean pulse rate (98.97±16.23 to 88.91±14.03; p<0.001) and the mean dyspnea severity (5.6±1.97 to 3.45±1.97; p<0.0001) decreased after two weeks of intervention. besides, the mean total qol and its dimensions, including general health (p<0.0001), physical status (p<0.0001), emotional status (p = 0.036), and social function (p < 0.0001) of patients had significantly increased after intervention. table 2 compares the measured outcomes before and after two weeks of pulmonary rehabilitation in studied cases. 4. discussion based on the findings of this study, it seems that two-week exercise-based pulmonary rehabilitation could be effective in increasing the o2 saturation, decreasing dyspnea and pulse rate, and improving the qol of severe covid-19 patients after discharge from intensive care unit. restrictive pulmonary changes and reduced diffusion capacity in patients diagnosed with moderate to severe covid-19 may lead to long-term functional limitations, as well as reduced qol in such patients. considering the previous studies, it appears that pulmonary rehabilitations may be helpful for patients diagnosed with acute respiratory distress syndrome as a consequence of covid-19 (15, 21-23). overall, beneficial impacts of rehabilitation have been clearly exhibited in a wide range of health conditions, and in patients with pulmonary diseases such as copd, rehabilitation reduces dyspnea and improves health-related quality of life (24). since short-term benefits have been reported for pr by patients, to ensure long-term effects, maintenance of physical activity and healthy lifestyles should be enforced by providing personalized home-based rehabilitation programs or referring the patients to long-term rehabilitation outpatient centers with an integrated model of care (6). a variety of studies revealed that pulmonary rehabilitation improved the spo2 in patients who survived covid-19 (5, 18, 19, 25, 26). the present study results were consistent with the mentioned studies. in this study, like the huang (27) and mcgregor (28) studies, the mean pulse rate significantly decreased after rehabilitation programs. also, the average pulse rate reduced, in line with the studies by alahmri (21) and huang et al. (2004), which showed that the patients recovered pulse rate after rehabilitation (27). additionally, in this study, the average of dyspnea reduced, which was in line with huang (27) and mcgregor et al.’s findings (28). this improvement was probably not only related to pr but also to the natural recovery process of the disease (29). moreover, in terms of quality of life, a significant increase was reported in patients enrolled in the study after two weeks of the exercise-based pulmonary rehabilitation. like the present study, recent studies demonstrated that pulmonary rehabilitation may improve the quality of life in patients diagnosed with covid-19 (19, 28, 30). a study conducted by mcgregor revealed that pulmonary rehabilitation could improve the general health status of patients with covid-19 (28). in the present study, exercise-based pulmonary rehabilitation improved the general health status of enrolled patients, as well as other sub-domains of qol questionnaire. in recent studies, physical status, emotional status, and social function of patients were improved in patients who underwent pulmonary rehabilitation (24, 28, 30, 31). severe covid-19 cases required prolonged icu stay and intubation; therefore, they had more physical and psychosocial impairments post-icu, but recovered following pr. further controlled and long-term studies are required to better understand the role of pr post-covid-19 (29). unfortunately, in this study we faced some restrictions. the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. rayegani et al. 4 table 2: comparing the status of studied variables before and after two weeks of exercise-based pulmonary rehabilitation variable mean ± sd p value spo2 (%) before 90.71 ± 3.97 <0.0001 after 95.11 ± 1.96 pulse rate (/minutes) before 98.97 ± 16.23 <0.001 after 88.91 ± 14.03 dyspnea severity* before 5.6 ± 1.97 <0.0001 after 3.45 ± 1.94 quality of life (total)# before 35.5 ± 13.73 <0.0001 after 51.05± 20.30 general health before 50.95 ± 17.88 <0.0001 after 57.78 ± 17.09 physical status before 1.37 ± 0.79 <0.0001 after 38.85 ± 23.09 emotional status before 49.21 ± 23.61 <0.036 after 57.14 ± 24.63 social function before 40.35 ± 21.88 <0.0001 after 51.42 ± 24.00 *: using borg scale; #: using sf-36 questionnaire. sd: standard deviation. lack of awareness of patients and specialists regarding the role of outpatient’s rehabilitation, caused late referral of patients to relevant centers for help and to reduce diseaserelated complications like dyspnea. also, due to long-term and heavy hospitalization costs of medical treatment of patients with severe covid-19 in icu and having physical and psychological fatigue related to the disease, and also being worried about re-infection or the spread of disease on the way to rehabilitation clinic, time-consuming pr exercises were not welcomed by some patients and they insisted on having just one training session instead of two weeks pr. however, giving educational brochures related to treatment sessions and encouraging the patients to work out through helping them feel recovered after exercises were the strengths of our study. 5. limitations it should be mentioned that our study had several limitations, which need to be considered when interpreting findings; firstly, the small sample size of covid-19 patients that were rehabilitated and also the absence of follow-up after pr due to limited research time and the probability of losing samples; secondly, the lack of a control group of covid-19 patients post-icu who were not rehabilitated; and thirdly no causal role of rehabilitation can be assumed with certainty. 6. conclusion based on the findings of this study, it seems that two-week exercise-based pulmonary rehabilitation could be effective in increasing the o2 saturation, decreasing dyspnea and pulse rate, and improving the qol of severe covid-19 patients after discharge from intensive care unit. 7. declarations 7.1. acknowledgments we gratefully acknowledge the contribution of patients who participated in this study, their family members, dr. kianmehr aalipour(research assistance in pm&r research center) and the covid-19 intensive care unit at shohada-etajrish hospital, affiliated to shahid beheshti university of medical sciences. 7.2. authors’ contributions leila angooti carried out the process of data gathering. leila angooti wrote the manuscript with support from mansoor rayegani, and rama bozorgmehr. mansoor rayegani, rama bozorgmehr helped supervise the project. mansoor rayegani, rama bozorgmehr, leila angooti and amir hossein mahdi kaghazi performed the manuscript proofing. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 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9(1): e63 or i g i n a l re s e a rc h topical lidocaine plus diclofenac as a local anesthetic agent in central venous catheterization; a randomized controlled clinical trial reza azizkhani1, maysameh shahnazari sani1, farhad heydari1∗, mina saber2, sarah mousavi3 1. department of emergency medicine, faculty of medicine, isfahan university of medical sciences, isfahan, iran. 2. department of dermatology, school of medicine, isfahan university of medical sciences, isfahan, iran. 3. department of clinical pharmacy and pharmacy practice, school of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran. received: july 2021; accepted: august 2021; published online: 15 september 2021 abstract: introduction: various methods of analgesia can be used to reduce or prevent procedural pain in emergency department (ed). this study aimed to evaluate the effectiveness of topical lidocaine-diclofenac combination compared to lidocaine-prilocaine combination (xyla-p) in reduction of the pain during central venous catheter (cvc) insertion. methods: in this randomized clinical trial, 100 adult patients requiring cvc insertion in the ed were enrolled. these patients were randomly divided into two groups. the site of cvc insertion was covered with 2 g of topical xyla-p cream in the first group, and 2 g of topical lidocaine-diclofenac cream in the second group. the primary outcome was the pain during cvc implantation. the secondary outcomes were physician satisfaction and the incidence of side effects. results: on the visual analog scale (vas), the pain score during cvc insertion was significantly lower in the second group (p = 0.027). however, there was no difference in pain scores during lidocaine injection between the two groups (p = 0.386). also, there was no significant difference in the rate of side effects between the two groups (p = 1.0). the physician’s satisfaction with the first group was significantly lower than the second group (p = 0.042). conclusion: although the cvc insertion pain was significantly lower in patients who received the topical combination of lidocaine plus diclofenac, there was no clinically important difference between the two groups and both topical anesthetics were effective and safe in reducing pain intensity. also, lidocaine-diclofenac combination cream was more cost-effective than xyla-p cream. keywords: diclofenac; anesthetics, local; lidocaine; central venous catheters; pain management cite this article as: azizkhani r, shahnazari sani m, heydari f, saber m, mousavi s. topical lidocaine plus diclofenac as a local anesthetic agent in central venous catheterization; a randomized controlled clinical trial. arch acad emerg med. 2021; 9(1): e63. https://doi.org/10.22037/aaem.v9i1.1389. 1. introduction central venous catheter (cvc) insertion is one of the most frequently performed invasive procedures in the emergency department (ed), which is associated with pain, anxiety, and discomfort (1, 2). the pain felt during the procedure is commonly reduced with the use of local anesthetics such as lidocaine. however, injection of local anesthetics itself may ∗corresponding author: farhad heydari; department of emergency medicine, alzahra hospital, sofeh ave, keshvari blvd., isfahan, iran. tel: +989131367643, email: farhad_heidari@med.mui.ac.ir, orcid: https://orcid.org/0000-0002-6296-0045. be associated with pain at the site of injection (1, 3). most clinicians believe that the local anesthetic injection will cause more pain than subsequent procedures, such as anchoring the catheter to the skin with sutures or eventually threading the dilator over the guidewire (4). pain during catheterization can cause anxiety and may negatively affect the treatment received. ensuring patient comfort is also important for increasing cooperation and contributing to procedure facilitation, thus reducing the risk of insertion failure or catheter malpositioning (5). various methods of analgesia can be used to reduce or prevent procedural pain. using topical anesthetics is an available, low-cost, and effective method to achieve analgethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. azizkhani et al. 2 sia. topical drug administration has clear advantages over other routes of administration, such as high levels of efficacy, more safety, and patient compliance. there is good evidence that adults benefit from reducing discomfort and anxiety by using an effective topical analgesic cream at the site of the procedure (6-9). for optimal pain management, eds have a vast variety of protocols for reducing pain. local anesthesia with xyla-p cream 5% (2.5% lidocaine and 2.5% prilocaine) has been shown to effectively reduce pain associated with minor procedures such as needle punctures (7, 9). another option is a nonsteroidal anti-inflammatory drug (nsaid), such as transdermal diclofenac patch (tdp), which is available and effective in reducing chronic pain by reducing prostaglandin synthesis (10-12). both lidocaine and diclofenac have analgesic, antiinflammatory, and antibiotic effects (10-13). also, lidocaine and diclofenac have a synergistic analgesic effect (14, 15). the dual mechanism of action of these substances on the cellular level is functionally synergistic in pain control. the combination of these agents results in a more long-lasting analgesia than that obtained with any of the substances alone (14). the pathophysiological mechanisms of pain are complex; therefore, combining active drugs with multiple mechanisms and synergistic action is a potentially more effective therapeutic approach to pain management than conventional monotherapy (6). this study aimed to evaluate the effectiveness of topical lidocaine-diclofenac combination compared to the xyla-p cream in reduction of the pain during cvc insertion. 2. methods 2.1. study design and setting this prospective randomized double-blind clinical trial was conducted in the ed of two university teaching hospitals (alzahra and kashani hospitals) in isfahan, iran, from january 2020 to april 2021. the study was approved by the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1398.063). the trial was registered on the iranian registry of clinical trials under the number irct20180129038549n11. all patients provided written informed consent for participation in the trial. 2.2. participants all adult patients requiring cvc insertion in the ed consented to participating and were enrolled in the study. patients were included in the study if they were older than 18 years, awake, alert, and oriented, and their medical condition was stable enough to allow cvc to be inserted within about 1 hour. patients with visual, mental, or verbal disorders, a history of an allergic reaction to local anesthetics, a history of favism, methemoglobin, renal and liver disease, skin diseases at or around the cvc insertion site, and a history of drug addiction, a history of analgesic use within 24 hours before the procedure, were excluded. also, patients were excluded if the venous catheter placement was not successful the first time (skin puncture was repeated more than once). 2.3. interventions the patients were randomly allocated to receive one of the two topical anesthetics: xyla-p cream (lidocaine 2.5% and prilocaine 2.5%), or lidocaine-diclofenac cream (2% lidocaine and 1% diclofenac). randomization was based on a random-allocation software package (1:1). in the first group (lp group), the site of cvc insertion was covered with 2 gr of xyla-p cream (tehran chemie pharmaceutical company, iran). in the second group (ld group), the site of cvc insertion was covered with 2 g of a fixed-dose combination containing 1% diclofenac (sobhan darou company, iran) and 2% lidocaine (sina darou company, iran) cream. the topical anesthetic was applied on a 5 cm 2 surface area over the procedure site in a thick layer and covered with an occlusive dressing for at least 45 min before the cvc implantation. lidocaine-diclofenac cream was prepared in 30 g weighted tubes in collaboration with the faculty of pharmacology (isfahan university of medical sciences). it was matched with the xyla-p cream in terms of color, smell, and shape, as well as labeling. an independent investigator who was not involved in clinical management and data collection did the randomization and prepared topical creams every day. after 45 minutes (16), the dressing and cream were removed. the blinded investigator then injected 5 ml of 2% lidocaine through a 25-gauge needle. the investigator injected 3 ml of lidocaine directly superficial to the internal jugular vein, then injected 1 ml just to the left and 1 ml just to the right of the vein for anchoring stitches. five minutes after injection, an attempt was made to insert cvc into the right internal jugular vein using the anterior approach with ultrasound guidance. each patient received a 7 fr triple-lumen catheter via a non-tunneled approach. 2.4. data gathering all measurements were recorded by investigators blinded to randomization and the type of topical analgesia used. the pain was assessed using a visual analog scale (vas) from 0 to 10 (0: no pain, 10: the worst possible pain imaginable) (6, 7). the physician’s satisfaction was assessed using a 10-point verbal numeric rating scale from 0 to 10 (0: completely dissatisfied, 10: completely satisfied). the pain scores were reported by the patient after initial subcutaneous lidocaine injection, and just after cvc insertion. the physician’s satisfaction was recorded after the overall this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e63 procedure was completed. in the beginning of the study, patient characteristics (age, sex, and body mass index (bmi)) were recorded. during the study, an investigator evaluated the local side effects (erythema, urticaria, pruritus, and irritation). systemic effects (heart rate and systolic and diastolic blood pressure) were also recorded before intervention and after cvc insertion. the patients, physicians, and nurses who participated in the trial were blinded to the randomization. 2.5. outcomes the primary outcome was the intensity of pain during cvc implantation. the secondary outcomes were physician satisfaction and the incidence of side effects. 2.6. statistical analysis calculations showed that to detect a standard deviation of 0.90 for pain scores and a difference of 0.54 (17) on the vas scale (score range from 1 to 100) during cvc insertion with 95% confidence interval, and a power of 80%, a sample size of 45 patients was required in each group. thus, the study population of 50 patients per group was considered based on an anticipated dropout rate of 10% to ensure an adequately powered study. finally, the collected data was analyzed using spss software (ver. 25) and they were shown as mean ± standard deviation (sd) or frequency (%). chi-square test was used to compare qualitative data between the two groups, independent t-test and paired t-test were used to compare the mean of quantitative data, and univariate analysis was used to compare the mean pain score by adjusting confounding factors, such as age, sex, and bmi. the level of significance was considered less than 0.05. 3. results a total of 100 patients (50 patients per group) were enrolled in this study. all patients were included in the analysis (figure 1). the mean age was 36.15 ± 7.36 years (range 18–59); 61.0% were male. there was no statistically significant difference in baseline characteristics between the two groups (table 1). the mean pain scores during lidocaine injection and cvc insertion are reported in table 2. the pain scores during cvc insertion were significantly lower in the ld group compared to the lp group (3.74 ± 2.14 vs 4.60 ± 2.04, p = 0.027), however, there was no difference in pain scores during lidocaine injection between ld and lp groups (p = 0.386). the physician’s satisfaction in the ld group was higher than the lp group (p = 0.042). there was no episode of urticaria and edema at the site of application in either of the groups. there was no significant difference in the rate of side effects between the two groups (table 2). also, there was no significant difference in vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) between the ld and lp groups before and after the cvc insertion (p > 0.05) (table 3). 4. discussion according to the results of the present study, although the cvc insertion pain was significantly lower in patients who received the topical combination of lidocaine plus diclofenac, there was no clinically important difference between the two groups and both topical anesthetics were effective and safe in reducing pain intensity. also, lidocaine-diclofenac combination cream is more cost-effective than xyla-p cream. procedural pain relief or control not only reduces anxiety and fear in patients but also increases their cooperation and contributes to the ease of the procedure and improves overall patient satisfaction. a cvc insertion can cause much pain and anxiety. one way to reduce this pain and anxiety is to use topical and local anesthesia. linares-gil et al. (2018) showed that a topical formulation containing lidocaine plus diclofenac was safe and more effective than the topical lidocaine alone for reducing the pain intensity during the first three days after surgery in benign anorectal surgery (15). topical nsaids are effective in decreasing acute and chronic pain by inhibiting prostaglandin synthesis at the site of application (18). khalili et al. (2014) demonstrated that the diclofenac gel significantly reduced the pain severity associated with vein catheter insertion and was more effective than emla (containing lidocaine/prilocaine) (17). they suggested using diclofenac gel rather than emla because it was more cost effective and effective in reduction of pain with fewer side effects. babaieasl et al. (2019) compared the efficacy of emla and topical diclofenac patch (tdp) in attenuating peripheral venous catheters pain and phlebitis. emla and tdp had similar analgesic effects, but the incidence of phlebitis in the tdp group was significantly lower than the emla group (19). contrary to other studies, deshpande et al. (2010) showed higher effectiveness of emla cream in comparison to diclofenac transdermal patch for attenuation of the pain caused by iv cannulation among adult patients (18). these studies/this study, similar to the present study, demonstrated the efficacy of topical diclofenac in reducing pain during venous cannulation. the pain caused by lidocaine injections is often considered a necessary problem, but there are several ways to reduce it. buffering and warming of the lidocaine solution before injection are probably the simplest and most effective measures (20, 21). another measure to reduce injection pain is to use topical anesthesia. in the present study, the application of both creams was effective in decreasing the pain of lidocaine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. azizkhani et al. 4 table 1: comparing the baseline characteristics of patients between two groups variables lp group (n=50) ld group (n=50) p value sex male 33 (66.0) 28 (56.0) 0.305 female 17 (34.0) 22 (44.0) age (year) 36.84 ± 7.60 35.45 ± 7.37 0.084 bmi (kg/m2 ) 28.50 ± 2.51 28.32 ± 2.36 0.713 data are presented as mean ± standard deviation or frequency (%). lp: lidocaine-prilocaine; ld: lidocaine-diclofenac; bmi: body mass index. table 2: comparison of pain scores, physician satisfaction, and side effects between the two groups variables lp group (n=50) ld group (n=50) p value pain (based on vas) during lidocaine injection 1.68 ± 0.41 1.62 ± 0.47 0.386 during cvc insertion 4.60 ± 2.04 3.74 ± 2.14 0.027 physician satisfaction mean ± sd 6.40 ± 2.040 7.26 ± 2.136 0.042 side effects erythema 1 (2.0) 1 (2.0) na irritation 1 (2.0) 1 (2.0) data are presented as mean ± standard deviation (sd) or frequency (%). lp: lidocaine-prilocaine; ld: lidocaine-diclofenac; cvc: central venous catheter; vas: visual analogue scale. table 3: comparison of vital signs before and after central venous catheter insertion in the two groups variables vital signs p value systolic blood pressure (mmhg) lp group 125.43 ± 15.78 122.69 ± 15.71 0.383 ld group 123.38 ± 14.73 124.87 ± 15.56 0.465 diastolic blood pressure (mmhg) lp group 79.71 ± 9.95 81.45 ± 10.13 0.214 ld group 80.35 ± 10.65 82.65 ± 10.11 0.578 heart rate (beat /minute) lp group 82.88 ± 11.65 85.58 ± 12.23 0.245 ld group 82.61 ± 11.09 84.64 ± 11.72 0.212 data are presented as mean ± standard deviation. lp: lidocaine-prilocaine; ld: lidocaine-diclofenac. injection. it should be noted that lidocaine injections as deep as 2–3 cm in the neck were performed in the current study, in contrast to intradermal and immediate subdermal injections most often received in the hand or arm, as in most other similar studies. culp et al. (2008) compared various local analgesics regarding their efficacy of pain reduction during central venous catheter placement. there was no difference in pain scores during lidocaine injection between lidocaine and buffered lidocaine groups. contrary to the present study, they showed that the mean score of pain during lidocaine injection was higher than pain during the insertion of the catheter (22). but in the present study, mean pain score during lidocaine injection was lower than cvc insertion in both groups. since there was no control group in this study, we could not have evaluated the pain of cvc insertion in patients who only received lidocaine injection without any topical analgesia. selvi et al. demonstrated that topical vapocoolant spray can be used before digital nerve blocking to reduce procedural pain (23). heydari et al. showed that local cutaneous ketamine is as effective as emla for reducing the pain during venipuncture (7). there was no episode of urticaria or edema at the site of application in either of the groups. both erythema and irritation were observed in 2.0% of the participants in each group. there was no significant difference in the rate of side effects between the two groups. similarly, agarwal a et al. (2006) demonstrated no incidence of blanching at the site of dtp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e63 figure 1: consort flow diagram of the study. patch (10). in other articles, the most common side effect was blanching in the dtp and emla groups. these results showed that the use of topical diclofenac (patch or gel) before intravenous cannulation can be an effective and safe way to reduce pain (17, 18). 5. limitations small sample size and evaluation of pain severity via a subjective method (vas) can be considered as limitations of the present study. there was no control/placebo group for the comparison of vas score to lidocaine injection. minimum duration of 45 minutes was allowed for the application of both creams, which is a rather long period in the ed, as most of the studies using emla and nsaids for topical application have shown that 45-60 minutes is required for their full effect. the skin thickness affects topical absorption of the drug, so further studies can assess this matter more accurately. it is also suggested to do future studies to evaluate the effect of the present drug combination at different times and in different procedures to generalize the results of the present study to the community with more certainty. 6. conclusion according to the results of the present study, although the cvc insertion pain was significantly lower in patients who received the topical combination of lidocaine plus diclofenac, there was no clinically important difference between the two groups and both topical anesthetics were effective and safe in reducing pain intensity. also, lidocaine-diclofenac combination cream is more cost-effective than xyla-p cream. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. azizkhani et al. 6 7. declarations 7.1. acknowledgments the present article was extracted from the thesis by dr. maysameh shahnazari sani to achieve her specialist degree in emergency medicine from isfahan university of medical sciences. the authors would like to express their gratitude to the staff of the ed of al-zahra and kashani hospitals, isfahan, iran. 7.2. funding and supports this study was funded by isfahan university of medical sciences. 7.3. author contribution r.a., m.s.s., f.h., s.m., and m.s.; contributed to conception, study design, and data collection and evaluation. r.a., m.s.s., f.h.; contributed to statistical analysis, and interpretation of data. r.a., f.h.; were responsible for overall supervision. f.h. and m.s.s; drafted the manuscript, which was revised by r.a., m.s. and s.m. all authors edited and approved the final version of this paper for submission, and also participated in the finalization of the manuscript and approved the final draft. 7.4. conflict of interest the authors declare no conflict of interest. references 1. donati a, damiani e, adrario e, romano r, pelaia p. pain and discomfort management during central venous catheter insertion. indian journal of critical care medicine: peer-reviewed, official publication of indian society of critical care medicine. 2014;18(7):417. 2. esmailian m, azizkhani r, najafi n. saline flush versus chest x ray in confirmation of central venous catheter placement; a diagnostic accuracy study. emergency. 2017;5(1):e75. 3. samantaray a. effects of dexmedetomidine on procedural pain and discomfort associated with central venous catheter insertion. indian journal of anaesthesia. 2014;58(3):281. 4. samantaray a, hanumantha rao m, sahu cr. additional analgesia for central venous catheter insertion: a placebo controlled randomized trial of dexmedetomidine and fentanyl. critical care research and practice. 2016;2016:9062658. 5. nataloni s, 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peripheral neuromuscular pain. arzneimittelforschung. 2006;56(02):108-14. 15. linares-gil mj, valls j, hereu-boher p, nebot f, deramón b, diaz-munió e, et al. topical analgesia with lidocaine plus diclofenac decreases pain in benign anorectal surgery: randomized, double-blind, and controlled clinical trial. clinical and translational gastroenterology. 2018;9(11):210. 16. fujimoto k, adachi h, yamazaki k, nomura k, saito a, matsumoto y, et al. comparison of the pain-reducing effects of emla cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: a multi-center, open-label, randomized crossover trial. plos one. 2020;15(3):e0230372. 17. khalili s, safavi m, rezaei r, bidmeshki m, shirzad f, nasiri m. the effectiveness of diclofenac gel and eutectic mixture of local anesthetic cream on vein puncture this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded 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bicarbonate-buffered lidocaine as a painkiller for patients with trauma. journal of injury and violence research. 2015;7(2):87. 22. culp jr wc, yousaf m, lowry b, mccowan tc, culp wc. pain and efficacy of local anesthetics for central venous access. local and regional anesthesia. 2008;1:11-5. 23. selvi f, bedel c, akçimen m. evaluation of vapocoolant spray effect on pain reduction during digital nerve block: a randomized clinical trial. the american journal of emergency medicine. 2021;50:260-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e27 or i g i n a l re s e a rc h thoracic injury rule out criteria in prediction of traumatic intra-thoracic injuries; a validation study setareh asgarzadeh1, bahareh feizi 2, farhad sarabandi1∗, morteza asgarzadeh3 1. clinical research development center, amir-almomenin hospital, islamic azad university, tehran medical sciences branch, tehran, iran. 2. emergency department, pasteur hospital, bam university of medical sciences, bam, iran. 3. harvard t.h. chan school of public health, 667 huntington avenue, boston, ma, 02115. received: august 2016; accepted: october 2016; published online: 10 january 2017 abstract: introduction: doing chest x ray (cxr) for all trauma patients is not efficient and cost effective due to its low diagnostic value. the present study was designed aiming to evaluate the diagnostic accuracy of thoracic injury rule out criteria (tirc) in prediction of traumatic intra-thoracic injuries and need for cxr. methods: the present study is a prospective cross-sectional study that has been carried out to evaluate the accuracy of tirc model in screening blunt multiple trauma patients in need of cxr for ruling out intra-thoracic injuries. results: 1518 patients with the mean age of 33.53 ± 15.42 years were enrolled (80.4% male). the most common mechanisms of trauma were motor car accident (78.8%) and falling (13.6%). area under the roc curve, sensitivity, and specificity of model in detection of traumatic thoracic injuries was 0.95 (95% ci: 0.93 – 0.97), 100 (95% ci: 87.0 – 100), and 80.1 (95% ci: 78.0 – 82.1), respectively. brier score for tirc was 0.02 and its scaled reliability was 0.0002. conclusion: findings of the present study showed that tirc has high accuracy in prediction of traumatic intra-thoracic injuries and screening patients in need of cxr. keywords: thoracic injuries; decision support techniques; mass chest x-ray; diagnosis © copyright (2017) shahid beheshti university of medical sciences cite this article as: asgarzadeh s, feizi b, sarabandi f, asgarzadeh m. thoracic injury rule out criteria in prediction of traumatic intrathoracic injuries; a validation study. emergency. 2017; 5(1): e27. 1. introduction t raumatic injuries, as one of the causes of morbidity and mortality, inflict a big financial and social burden on health care systems (1). meanwhile, thoracic injuries are responsible for 20 -50% of trauma-related mortalities (2). numerous diagnostic tools exist for evaluating these injuries including computed tomography (ct) scan, chest x-ray (cxr), and ultrasonography accompanied by clinical examination. currently, cxr is considered as the first diagnostic test in traumatic thoracic injuries (3). however, study findings have shown that doing cxr for all patients is not efficient and cost effective due to its low diagnostic value (4, 5). therefore, researchers are seeking ways to use this tool only for patients with a higher risk of intra-thoracic injuries. in recent years, 2 clinical decision rules, namely ∗corresponding author: farhad sarabandi; department of pediatrics, amir_almomenin hospital, shirmohammadi avenue, naziabad, bahman square, tehran, iran. tel: 09122069521 email: farhad.sarabandi@gmail.com nexus chest in american population and thoracic injury rule out criteria (tirc) in iranian population have been introduced for screening patients in need of cxr following blunt trauma. based on nexus chest criteria, if any of the factors including age >60 years, rapid deceleration mechanism (falling from a height over 20 feet or being in a car accident with more than 40 mph speed), chest pain, intoxication, altered level of consciousness, distracting pain, and tenderness to chest wall palpation are present, the patient is at high risk regarding presence of injury and cxr is necessary (6). in tirc model age >60 years, hemodynamic instability, loss of consciousness, crepitation in auscultation, decreased pulmonary sounds, thoracic skin abrasion, and shortness of breath are factors predicting intra-thoracic injuries (7). these 2 models are just starting to be studied and they need to be validated in various populations. therefore, the present study was designed aiming to evaluate the diagnostic accuracy of tirc in prediction of traumatic intra-thoracic injuries and need for cxr. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. asgarzadeh et al. 2 2. methods 2.1. study design and setting the present study is a prospective cross-sectional study that has been carried out to evaluate the accuracy of tirc in screening patients in need of cxr in multiple trauma patients presented to the emergency department (ed) of pasteur hospital, bam, iran, during 1 year in 2014-2015. protocol of the present study was approved by hospital ethic committee. written informed consent was obtained from all the patients and the researchers adhered to the principles of helsinki declaration throughout the study. this project did not cause any disruption in the routine management of patients. 2.2. participants the study participants consisted of all blunt multiple trauma patients over 15 years old who were conscious and had stable hemodynamic. exclusion criteria included presence of penetrating chest trauma and not giving consent for participation in the study. 2.3. data gathering sample selection was done using non-randomized convenience sampling. after obtaining informed consent from the patient or their relative, the study checklist was filled. the checklist consisted of demographic data (age, gender, trauma mechanism), history and physical examination findings (distracting pain, loss of consciousness, tachypnea, chest pain, dyspnea, presence of thoracic skin abrasion due to trauma, tenderness in chest, chest deformity, tenderness in upper abdomen, crepitation in chest auscultation, decreased pulmonary sounds, and presence of crepitation), variables needed for tirc model, and cxr findings. an emergency medicine specialist was responsible for examining, gathering, and recording of data in various days and working shifts. immediately after data gathering, cxr was done for patients in 2 standard views of anterior-posterior and lateral, and the pathological findings (hemothorax; pneumothorax; fracture of rib, sternum, scapula, and clavicle; widened mediastinum; and lung contusion) were recorded. cxrs were interpreted and recorded by an emergency medicine specialist blinded to the clinical findings of the patients as well as the in-charge physician. to evaluate the accuracy of interpretations by the emergency physician, 5% of the cxrs were randomly selected and given to a radiologist for interpretation (inter-rater agreement between the radiologist and emergency physician was 100%). it should be noted that the radiologist was blind to both the emergency physician’s interpretation and clinical findings. final diagnosis of thoracic injury was done based on cxr. at times of suspicion to presence of a hidden injury, chest ct scan was done. 2.4. tirc model variables based on this model cxr is necessary for patients with unstable hemodynamics and loss of consciousness. in addition, conscious patients with stable hemodynamics that meet any of the factors including age >60 years, crepitation in auscultation, decrease in pulmonary sounds, thoracic skin abrasion, and shortness of breath, are categorized in the high risk group regarding probability of intra-thoracic traumatic injuries and should undergo cxr. 2.5. statistical analysis to determine sample size, considering the 6.5% prevalence of positive findings in multiple trauma patients’ cxr (8), a 95% confidence interval (ci) (α = 0.05), 90% power (β = 0.1) and maximum error of 1.5% (d = 0.015) in estimating prevalence of injury, minimum sample size was considered 1043. data were entered to stata 11.0 software. cxr findings were reported as frequency and percentage, and were divided into 2 groups of normal and abnormal. in the present study, to assess the validity of the model, a number of methods were used (9, 10) that included calculating the area under the receiver operating characteristic (roc) curve, sensitivity, specificity, positive and negative predictive value (ppv/npv ), and positive and negative likelihood ratio (plr/nlr) with 95% confidence interval (ci). to evaluate discrimination, calibration curve was drawn for assessing general calibration, and finally in evaluation of overall performance, brier score was used for assessing predictive accuracy and predictive reliability. it should be noted that in calibration curve, the perfect calibration is the reference line that has 0 intercept and slope of 1. the closer the slope and intercept of tirc model are to 1 and 0, respectively, the more perfect the model is for predicting presence or absence of injury in cxr (11). 3. results finally, data of 1518 patients with the mean age of 33.53 ± 15.42 years were gathered (80.4% male). table 1 shows baseline characteristics of studied patients. the most common mechanisms of trauma were motor vehicle collisions (42.1%) and falling down (28.2%). 401 (26.4%) had chest pain, 107 (7.1%) had chest wall tenderness, and 104 (6.8%) had a thoracic skin abrasion. based on cxr findings, 33 (2.2%) patients had at least 1 traumatic intra-thoracic injury. 3.1. discrimination area under the curve of tirc in detection of traumatic thoracic injuries was calculated to be 0.95 (95% ci: 0.93 – 0.97) (figure 1). considering the presence of at least one of the tric risk factors, sensitivity and specificity of model were 100 (95% ci: 87.0 – 100) and 80.1 (95% ci: 78.0 – 82.1), respectively. ppv of the test was 10.1 (95% ci: 7.1 – 14.0) and npv this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e27 figure 1: area under the receiver operating characteristic curve of thoracic injury rule out criteria (tirc). figure 2: the calibration plot for thoracic injury rule out criteria (tirc). was 100 (95% ci: 99.6 – 100). plr and nlr calculated were 5.0 (95% ci: 4.5 – 5.6) and 0 (95% ci: 0.0 – 0.0), respectively (table 2). calibration curve of tirc in detection of an intrathoracic injury has been presented in figure 2. this scatter plot has an intercept of 0.1 (95% ci: 0.01 -0.19) and a slope of 1.7 (95% ci: 1.3 -1.9) which shows the moderate calibration of this model. 3.2. overall performance brier score for tirc was 0.02 and its scaled reliability was 0.0002. these findings are indicative of this model’s high predictive accuracy and reliability. 4. discussion findings of the present study showed that tirc has high accuracy in prediction of traumatic intra-thoracic injuries and screening patients in need of cxr. there was no false negatable 1: baseline characteristics of studied patients variable number (%) age (year) < 60 1468 (96.7) ≥ 60 50 (3.3) gender male 1220 (80.4) female 298 (19.6) mechanism of trauma motor vehicle collision 1196 (78.8) falling down 207 (13.6) others 115 (7.6) vital sign (admission time) systolic blood pressure (mmhg) 119.2±9.1 diastolic blood pressure (mmhg) 78.2±14.9 spo2 (%) 97.7±2.9 respiratory rate (1/minute) 13.6±1.8 glasgow coma scale 15 1468 (96.7) less than 15 50 (3.3) dyspnea yes 42 (2.8) no 1476 (97.2) distracting pain yes 399 (26.3) no 1119 (73.7) thoracic skin abrasion yes 104 (6.8) no 1414 (93.2) chest deformity yes 8 (0.5) no 1510 (99.5) chest wall tenderness yes 107 (7.1) no 1411 (92.9) crepitation yes 16 (1.0) no 1502 (99.0) abdominal tenderness yes 25 (1.6) no 1493 (98.4) decrease in pulmonary sounds yes 37 (2.4) no 1481 (97.6) chest wall pain yes 732 (25.20) no 2173 (74.80) tive result in this model and this indicates the proper power of this instrument to rule out intra-thoracic injury following blunt trauma. based on the findings of this study, if tirc clinical decision rule was used, only 328 (21.6%) of the 1518 studied patients would undergo cxr. this finding shows that using tirc will lead to a significant decrease in unnecessary cxrs. in the studied population, 1485 (97.9%) of the cxrs were without any pathologic finding and tirc predict 1190 (80.1%) of them. this finding is in line with 2 previous studthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. asgarzadeh et al. 4 table 2: screening performance characteristics of thoracic injury rule out criteria (tirc) in detection of intra-thoracic injuries characteristics* value (95%ci) area under the curve 0.95 (0.93 0.97) sensitivity 100.0 (87.0 100.0) specificity 80.1 (78.0 82.1) positive predictive value 10.1 (7.1 14.0) negative predictive value 100.0 (99.6 100.0) positive likelihood ratio 5.0 (4.5 5.6) negative likelihood ratio 0.0 (0.0 0.0) true positive 33 true negative 1190 false positive 295 false negative 0 ∗ values given are based on presence of at least one of the following symptoms: age over 60, crepitation, loss of consciousness, decrease in pulmonary sounds, chest wall pain, chest wall tenderness, dyspnea, and skin abrasion; ci: confidence interval. ies. in a study by frouzanfar et al., it was shown that using this tool reduces unnecessary cxrs by 63.5% (7). this rate was 67.7% in safari et al. study (11). in the safari et al. study, which was a multi-center one, evaluation of patients was done by different physicians while in the present study all evaluations were done by one emergency medicine specialist. this might be the reason for the higher screening value of tirc in this study. in comparing tirc with nexus chest model, it is revealed that both models have similar and good value in screening of patients for performing cxr. a study by rodriguez et al. aiming to validate nexus chest, indicated the 98.5% sensitivity of this tool in screening traumatic intra-thoracic injuries (12) while this rate was 100% for tirc. however, it seems that fewer factors in tirc can be advantageous for using it in clinic. in addition, data such as height of falling and speed of the vehicle at the time of accident (which are required in nexus chest) are not readily available in many cases, especially in developing countries. however, it is worth noting that validation of nexus chest has only been done in the american population and validation of tirc has only been done in the iranian population. therefore, further studies are needed on both in other settings and geographical areas to ensure their validity. 5. limitation one of the limitations of the present study is being carried out in 1 center. therefore, the results may not be easily generalized. however, since the findings are in line with similar previous studies, it seems that being single centered has not affected the generalizability of the data. additionally, convenience sampling was used, which raises the probability of selection bias. however, unlike previous studies (11, 12), patient evaluation was done by a single emergency medicine specialist and cxr interpretation was done by another single emergency medicine specialist, which eliminates the effect of difference in assessor in these areas. 6. conclusion findings of the present study showed that tirc has high accuracy in prediction of traumatic intra-thoracic injuries and screening patients in need of cxr. there was no false negative result in this model and this indicates its proper power to rule out thoracic injury. 7. appendix 7.1. acknowledgements authors would like to thank all the staff of emergency department of pastor hospital, bam, kerman, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. nseir s, zerimech f, fournier c, lubret r, ramon p, durocher a, et al. continuous control of tracheal cuff pressure and microaspiration of gastric contents in 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2014. 16. nadi e, nekoie b, mobaien a, moghimbeigi a, nekoie a. evaluation of the etiology of nosocomial pneumonia in the icus of the teaching hospitals of hamadan university of medical sciences. scientific journal of hamadan university of medical sciences. 2011;18(1):26-32. 17. carlson kk, louis s. advanced critical care nursing. st louis. 2009. 18. sabery m, shiri h, moradiance v, taghadosi m, gilasi hr, khamechian m. the frequency and risk factors for earlyonset ventilator-associated pneumonia in intensive care units of kashan shahid-beheshti hospital during 20092010. kaums journal ( feyz ). 2013;16(6):560-9. 19. chung dr, song j-h, kim sh, thamlikitkul v, huang s-g, wang h, et al. high prevalence of multidrugresistant nonfermenters in hospital-acquired pneumonia in asia. american journal of respiratory and critical care medicine. 2011;184(12):1409-17. 20. klompas m, kleinman k, khan y, evans rs, lloyd jf, stevenson k, et al. rapid and reproducible surveillance for ventilator-associated pneumonia. clinical infectious diseases. 2012;54(3):370-7. 21. zarinfar n, sharafkhah m, bayat b, sgharfarazi a, masoomehsoofian. epidemiological factors of ventilatorassociated pneumonia (vap) among icu patients in valiasr hospital of arak. 2012. iranian journal of infectious diseases and tropical medicine. 2014;19(64). 22. nateghian a, omrani a, alipour z, haerinejad m. causes of ventilator associated pneumonia in pediatrics icu. iranian south medical journal. 2016;19(1):98-105. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e3 or i g i n a l re s e a rc h epidemiology and related risk factors of preterm labor as an obstetrics emergency ali asghar halimi asl1∗, saeed safari2, mohsen parvareshi hamrah2 1. department of pediatrics, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: november 2015; accepted: january 2016; published online: 8 january 2017 abstract: introduction: preterm birth is still a major health problem throughout the world, which results in 75% of neonatal mortality. preterm labor not only inflicts financial and emotional distress, it may also lead to permanent disability. the present study was conducted to determine therelated risk factors andpreventive measuresof preterm labor. methods: this retrospective cross-sectional study assessed all preterm labors, as well as an equal number of term labors, during seven years, at an educational hospital. probable risk factors of preterm labor were collected using medical profiles of participants by the aid of a pre-designed checklist. significant related factors of preterm laborwere used for multivariate logistic regression analysis with spss 21.0. results: 810 cases with the mean age of 28.33 ± 6.1 years were evaluated (48.7% preterm). multipartite; fetal anomaly; prenatal care; smoking; not consuming folic acid and iron supplements; in vitro fertilization; history of infertility, caesarian section, trauma, systemic disease, and hypertension; amniotic fluid leak; rupture of membranes; cephalic presentation; vaginal bleeding; placenta decolman; oligohydramnios; pre-eclampsia; chorioamnionitis; uterine abnormalities; cervical insufficiency; intercourse during the previous week; short time since last delivery; and mother’s weight significantly correlated with preterm labor. conclusion: based on the results of the present study, intercourse during the previous week, multipartite, short time from last delivery, preeclampsia, fetal anomaly, rupture of membranes, hypertension, and amniotic fluid leak, respectively, were risk factors for preterm labor. on the other hand, iron consumption, cephalic presentation, systematic disease, history of caesarian section, prenatal care, and mother’s weight could be considered as protective factors. keywords: premature birth; infant, premature; obstetric labor, premature; fetal membranes, premature rupture; emergencies © copyright (2017) shahid beheshti university of medical sciences cite this article as: halimi asl aa, safari s, parvareshi hamrah m. epidemiology and related risk factors of preterm labor as an obstetrics emergency. 2017; 5(1): e3. 1. introduction p reterm labor is an obstetrics emergency and a threat to population health. 75% of infant mortality is related to preterm labor (1, 2). preterm labor not only inflicts financial and emotional distress on the family, it may also lead to permanent disability (physical or neural damages) in infants. approximately one-third of preterm labor survivors suffer from severe long-term neurological disabilities, such as cerebral palsy or mental retardation (3). furthermore, preterm infants carry increased risk of a range of neurodevel∗corresponding author: ali asghar halimi asl; pediatrics department, shohadaye tajrish hospital, shardari street, tajrish square, tehran, iran. tel: 00989121592797, email: aliasgharhalimiasl@yahoo.com. opmental impairments and disabilities including behavioral problems, school learning difficulties, chronic lung disease, retinopathy of prematurity, hearing impairment, and lower growth attainment (4). over the last two decades, preterm birth rate has remained unchanged or even risen in most countries, despite the increased understanding of possible risk factors and their pathological mechanisms (5-7). although neonatal mortality rate has fallen globally between 1990 and 2009 (8), the absolute number and rate of preterm births has increased during this period. preterm birth was the second leading cause of death in children under 5 years old (9). in 2013, preterm birth rate in germany, brazilandunited states were 8.7%, 10.7 and 12%, respectively (10, 11). the vast majority (85%) of global preterm births occur in asia and africa, where health systems are weak and inadethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com aliasgharhalimiasl@yahoo.com aa. halimi asl et al. 2 quate (12, 13). in iran incidence of preterm labor was 7.2% in tehran, 5.5% in shiraz, and 8.4% in khorramabad (14-16). although in most cases preterm births occur idiopathically, fetal, uterine, and placental factors as well as maternal chronic diseases, can affect preterm birth (17). in the usa, 70% of preterm births were idiopathic and the rest were due to preeclampsia (50%), fetal distress (25%) and abruption (25%) (18). in another study, preterm multifetal pregnancies and hypertension were introduced as the major factors affecting preterm birth (19). in order to determine the incidence and etiologic factors of preterm labor, the present study was conducted on newborns at the obstetrics emergency department of shohadaye tajrish hospital with a view to identifying preventive measures. 2. methods 2.1. study design and setting this retrospective cross-sectional study assessed all preterm labors during seven years, from march 2008 until march 2015, at shohadaye tajrish hospital, tehran, iran, by normal vaginal delivery or cesarean section, using census method. an equal number of term labors were selected by simple random sampling as the control group. the study protocol was approved by the ethical committee of shahid beheshti university of medical sciences. the researchers adhered to the principles of helsinki declaration, as well as confidentiality of patient data and patient rights. 2.2. data gathering probable risk factors of preterm labor such as: mother’s age, weight, body mass index, and job; type of delivery (natural or caesarian section), baby’s sex and weight; apgar score at 1 and 5 minutes; multi-partite; fetal abnormalities;prenatal care; smoking, alcohol, and opium abuse; history of folic acid, metformin, and iron consumption; history of in vitro fertilization, infertility, abortion, preterm delivery, trauma, vaginal bleeding, intra uterine fetal death (iufd), dental infection, respiratory infection, and caesarian section; amniotic fluid leak; rupture of membranes; cephalic presentation; vaginal infection; placenta decolman; placenta praevia; polyhydramnios; oligohydramnios; urinary tract infection; systemic disease; anemia; hypertension; preeclampsia; eclampsia; chorioamnionitis; uterine abnormalities, cervical insufficiency; placental insufficiency; polycystic ovary; history of intercourse during the previous week; and timefrom last delivery were collected using medical profiles of participants by the aid of a pre-designed checklist. incomplete patient files were excluded. short time from last delivery was considered to be 1 year. 2.3. statistical analysis the data were analyzed with spss software version 21.0. qualitative data were reported as mean ± standard deviation and quantitative ones as frequency and percentage. frequency of all risk factors were compared between the two groups (preterm and term) using chi square and fisher’s exact tests. multivariate logistic regression analysis was applied to independent statistically significant factors for developing a predictive model and odds ratio (or) of each risk factor was calculated. p value under 0.05 was considered significant. 3. results: 810 cases with the mean age of 28.33 ± 6.1 (14 -64) years were evaluated (48.7% preterm). table 1 depicts baseline characteristics of the studied patients. among the studied risk factors, multipartite (p < 0.001), fetal anomaly (p = 0.022), prenatal care (p = 0.005), smoking (p = 0.004), not consuming folic acid (p = 0.004), not consuming iron supplements (p < 0.001), in vitro fertilization (p = 0.014), history of infertility (p = 0.005), amniotic fluid leak (p < 0.001), rupture of membranes (p < 0.001), history of caesarian section (p < 0.001), cephalic presentation (p < 0.001), history of trauma (p = 0.015), vaginal bleeding (p < 0.001), placenta decolman (p = 0.003), oligohydramnios (p < 0.001), history of systemic disease (p < 0.001), history of hypertension (p = 0.006), pre-eclampsia (p = 0.001), chorioamnionitis (p = 0.003), uterine abnormalities (p = 0.034), cervical insufficiency (p = 0.001), intercourse during the previous week (p < 0.001), short time since last delivery (p = 0.040), and mother’s weight (p = 0.012) significantly correlated with higher risk of preterm labor. table 3 shows the results of multivariate logistic regression analysis.intercourse during the previous week (or: 23.1), multipartite (or: 21.8), short time from last delivery (or: 4.8), pre-eclampsia (or:4.7 ), fetal anomaly (or:3.6), rupture of membranes (or:3.5), hypertension (or:3.3), and amniotic fluid leak (or:2.1), respectively, were risk factors andiron consumption (or:0.3), cephalic presentation (or:0.4), systematic disease (or:0.6), history of caesarian section (or: 0.6), prenatal care (or:0.6), and mother’s weight (or:0.98), respectively, were preventive factors of preterm labor. 4. discussion based on the findings of the present study, independent related factors ofpreterm labor were multipartite, fetal anomaly, prenatal care, smoking, not consuming folic acid, not consuming iron supplements, in vitro fertilization, history of infertility, amniotic fluid leak, rupture of membranes, history of caesarian section, cephalic presentation, history of trauma, vaginal bleeding, placenta decolman, oligohydramnios, history of systemic disease, history of hypertenthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e3 table 1: baseline characteristics of studied patients based on age of delivery variable term preterm p value age (year) 28.25 ± 5.9 28.37 ± 6.34 0.766 weight (kg) 76.38 ± 13.11 73.78 ± 14.19 0.012 job home keeper 319 (46.9) 361 (53.1) 0.626 employee 7 (50) 7 (50) type of delivery natural 302 (54) 257 (46) 0.002 caesarian section 101 (42.8) 135 (57.2) baby’s sex boy 205 (46.8) 233 (53.2) 0.065 girl 195 (55.1) 159 (44.9) baby’s weight (gram) 3184 ± 542 2080 ± 1012 < 0.001 apgar (1t h minute) 7.1 ± 2.3 5.7 ± 3.0 0.076 apgar (5t h minute) 8.9 ± 0.6 7.9 ± 2.4 < 0.001 data are presented as mean ± standard deviation or number (%). sion, preeclampsia, chorioamnionitis, uterine abnormalities, cervical insufficiency, intercourse during the previous week, short time since last delivery, and mother’s weight. intercourse during the previous week, multipartite, short time from last delivery, preeclampsia, fetal anomaly, rupture of membranes, hypertension, and amniotic fluid leak, respectively, were risk factors for preterm labor. on the other hand, iron consumption, cephalic presentation, systematic disease, history of caesarian section, prenatal care, and mother’s weight could be considered as protective factors. preterm labor, as mentioned before, is a major obstetric and pediatric challenge because it is a common, persistent, and often devastating condition with considerable medical, economic, emotional, and social impact (20). it is thought to be a syndrome initiated by multiple mechanisms, consisting of infection or inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress, and other immunologically mediated processes. however, adefined mechanism cannot be established in most cases (21). despite advancesin understanding risk factors and mechanisms related to preterm labor, the preterm labor rate has risen in most industrialized countries. in the usa, preterm labor rate increased from 9.5% in 1981 to 12.7% in 2005 (22, 23). in the present study, low maternal weight has increased the risk of preterm labor, while in retrospective studies, this factor weakly correlated with preterm birth (24-26). although most of the term births were via natural delivery and most of the preterm laborsvia caesarian delivery, no significant relationship was found. the mean age of mothers with preterm laborin this study, were the same as mothers with term infants, while the incidence of prematurity in different studies was greater in old mothers (27, 28). several studies have demonstrated that adequate utilization of pre-natal care is accompanied with improved birth weights and lower risk of preterm birth. on the other hand, inadequate pre-natal care is often referred to as a risk factor for poor pregnancy outcomes. in our study, women who had nowell-designed pre-natal care program, were atrisk for preterm labor (29, 30). infections and vaginosis are well-known risk factors for preterm birth. in a study, presence of bacterial vaginosis at 28 weeks gestation was associated with an increased risk of spontaneous preterm birth (31). nevertheless, these factors were not associated with preterm birth in our study. antibiotic therapy could either eliminate infections or modify their effects on pregnancy outcome (32-34). smoking has been linked to preterm labor, and in this study this factor hadan association with it (35, 36). although sexual activity, particularly intercourse, during pregnancy has been connected to preterm labor, because of direct effects of semen on initiating preterm labor or alteration of vaginal ph, there is evidence that shows sexual activity during pregnancy is not associated with preterm birth. in this study, intercourse during the previous week affected preterm birth (37). high levels of alcohol consumption during pregnancy have obvious adverse effects on fetal development, but in this project there is no consistency between use of alcohol and chance of preterm birth (38). various studies have suggested lower rates of preterm birth in women taking dietary supplements (39). dietary supplements taken before, but not after conception, were linked with a reduced rate of preterm birth; however, a placebo-controlled trial of vitamin supplementsin women before conception and 2 months after pregnancy, reported no effect on preterm birth rate (40, 41). our results showed that folic acid and iron consumption significantly decrease the rate of preterm birth. preterm rupture of fetal membranes leads to 30% of preterm births in industrialized countries. management, consists of maternal and fetal surveillance for labor, infection, and abruption, and administration this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com aa. halimi asl et al. 4 table 2: comparison of studied risk factors of preterm delivery between term and pre term pregnancy risk factor term n (%) preterm n (%) p value multipartite yes 3 (6.7) 42 (93.3) < 0.001 no 403 (53) 357 (47) fetal anomaly yes 8 (29.6) 19 (70.4) 0.022 no 398 (51.2) 380 (48.8) prenatal care yes 159 (56.8) 121 (43.2) 0.005 no 247 (47) 278 (53) smoking yes 0 (0) 8 (100) 0.004 no 406 (50.9) 391 (49.1) alcohol usage yes 0 (0) 1 (100) 0.496 no 406 (50.5) 398 (49.9) opium usage yes 4 (28.6) 10 (71.4) 0.083 no 402 (50.8) 389 (49.2) folic acidconsumption yes 149 (57.3) 111 (42.7) 0.004 no 257 (47.2) 288 (52.8) metforminconsumption yes 5 (62.5) 3 (37.5) 0.372 no 401 (50.3) 396 (49.7) iron consumption yes 371 (55.1) 302 (44.9) < 0.001 no 35 (26.5) 97 (73.5) in vitro fertilization yes 6 (26.1) 17 (73.9) 0.014 no 400 (51.2) 382 (48.8) history of infertility yes 26 (35.6) 47 (64.4) 0.005 no 380 (51.9) 352 (48.1) history of abortion yes 71 (51.1) 68 (48.9) 0.471 no 335 (20.3) 331 (49.7) history of preterm delivery yes 8 (36.4) 14 (63.6) 0.131 no 398 (50.8) 385 (49.2) history of iufd yes 8 (36.4) 14 (63.6) 0.131 no 398 (50.8) 385 (49.2) amniotic fluid leak yes 79 (33.3) 158 (66.7) <0.001 no 327 (57.6) 241 (42.4) rupture of membranes yes 30 (22.9) 101 (77.1) < 0.001 no 376 (55.8) 298 (44.2) history of caesarian section yes 142 (65.1) 76 (34.9) < 0.001 no 264 (45) 323 (55) cephalic presentation yes 343 (56.6) 263 (43.3) < 0.001 no 63 (31.7) 136 (68.3) history of trauma yes 3 (20.3) 12 (80) 0.015 no 403 (51) 387 (49) iufd: intrauterine fetal death. continued on next page this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e3 table 2: comparison of studied risk factors of preterm delivery between term and pre term pregnancy risk factor term n (%) preterm n (%) p value history of surgery yes 34 (54) 29 (46) 0.326 no 372 (50.1) 370 (49.9) vaginal bleeding yes 6 (18.8) 26 (81.3) < 0.001 no 400 (51.7) 373 (48.3) vaginal infection yes 5 (35.7) 9 (64.3) 0.200 no 401 (50.7) 390 (49.3) placenta decolman yes 3 (16.7) 15 (83.3) 0.003 no 403 (51.2) 384 (48.8) placenta praevia yes 4 (40) 6 (60) 0.365 no 402 (50.6) 393 (49.4) polyhydramnios yes 3 (37.5) 5 (62.5) 0.353 no 403 (50.6) 394 (49.4) oligohydramnios yes 12 (25) 36 (75) < 0.001 no 394 (52) 363 (48) urinary tract infection yes 65 (56.5) 50 (43.5) 0.095 no 341 (49.4) 349 (50.6) systemic disease yes 133 (60.2) 88 (39.8) < 0.001 no 273 (46.7) 311 (53.3) anemia yes 31 (51.7) 29 (48.3) 0.475 no 375 (50.3) 370 (49.7) history of hypertension yes 58 (40.6) 85 (59.4) 0.006 no 348 (52.6) 314 (47.4) preeclampsia yes 13 (27.7) 34 (72.3) 0.001 no 393 (51.8) 385 (48.2) eclampsia yes 1 (20) 4 (80) 0.181 no 405 (50.6) 395 (49.4) chorioamnionitis yes 1 (8.3) 11 (91.7) 0.003 no 405 (51.1) 388 (48.9) uterine abnormalities yes 6 (28.6) 15 (71.4) 0.034 no 400 (51) 384 (49) cervical insufficiency yes 0 (0) 10 (100) 0.001 no 406 (51.1) 389 (48.9) placental insufficiency yes 0 (90) 3 (10) 0.121 no 406 (50.6) 396 (49.4) polycystic ovary yes 1 (33.3) 2 (66.7) 0.493 no 405 (50.5) 397 (49.5) body mass index yes 12 (63.2) 7 (36.8) 0.187 no 394 (50.1) 392 (49.9) intercourse during the previous week yes 1 (6.3) 15 (93.8) < 0.001 no 405 (51.3) 384 (48.7) continued on next page this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com aa. halimi asl et al. 6 table 2: comparison of studied risk factors of preterm delivery between term and pre term pregnancy risk factor term n (%) preterm n (%) p value short time since last delivery yes 7 (30.4) 16 (69.6) 0.040 no 399 (51) 383 (49) history of dental infection yes 1 (14.3) 6 (85.7) 0.59 no 405 (50.8) 393 (49.2) history of respiratory infection yes 2 (50) 2 (500) 0.681 no 404 (50.4) 397 (49.6) iufd: intrauterine fetal death. table 3: the results of multivariate logistic regression analysis variable odds ratio (95% ci*) p value intercourse during the previous week 23.1 (2.7-194.2) 0.004 multipartite 21.8 (4.8-97.9) <0.001 short time from last delivery 4.8 (1.4-16.2) 0.012 preeclampsia 4.7 (1.9-11.6) 0.001 fetal anomaly 3.6 (1.1-11.2) 0.024 rupture of membranes 3.5 (2-6.2) <0.001 hypertension 3.3 (1.9-5.5) <0.001 amniotic fluid leak 2.1 (1.4-3.4) 0.001 mother’s weight 0.98 (0.96-0.99) 0.005 prenatal care 0.6 (0.04-0.09) 0.036 history of caesarian section 0.6 (0.4-0.9) 0.020 systematic disease 0.6 (0.4-0.9) 0.010 cephalic presentation 0.4 (0.2-0.6) <0.001 iron consumption 0.3 (0.2-0.6) <0.001 ci∗: confidence interval. of corticosteroids or antibiotics (42, 43). ruptures of the fetal membranes are remarkably seen in preterm birth. the availability of medical reproductive techniques has increased the number of multiple pregnancies. in addition, multiple pregnancies resulting from reproductive medical treatments are more common in women of advanced maternal age (44). the preterm birth rate for multiple pregnancies stands at 40-60% (45). multipartite and in vitro fertilization directly correlated with preterm birth. in our study, pre-eclampsia was 72.3% in preterm labor and 27.7% in term labors. in our study, history of chronic hypertension was seen in 59.4% of mothers with preterm labor and 40.6% in mothers with term labor. in other studies the most common maternal disease was hypertension (16). using the results of this study and similar onesto eliminate the risk factors and reinforcethe protective factors would be helpful in decreasing the rate of preterm labor and its human and social burden. yet, for accurately determining these factors, studies with better design, such as cohort studies, with proper follow-up period and large study population, are needed. since the studied hospital is a referral center for these patients, it represents the general population of the country to a great extent. still, the final decision regarding factors definitely affecting pre-term labor should be made after further studies. 5. conclusion based on the results of the present study, intercourse during the previous week, multipartite, short time from last delivery, preeclampsia, fetal anomaly, rupture of membranes, hypertension, and amniotic fluid leak, respectively, were risk factors for preterm labor. on the other hand, iron consumption, cephalic presentation, systematic disease, history of caesarian section, prenatal care, and mother’s weight could be considered as protective factors. 6. appendix 6.1. acknowledgements we would like to thank dr. m afrakhte, specialist of perinatology, medical staff of emergency department, and the manager of medical recordsunit of shohadaye tajrish hospital who provided help for this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e3 6.2. authors contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding support none 6.4. conflict of 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registers by eshre. human reproduction. 2012;27(9):2571-84. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e36 https://doi.org/10.22037/aaem.v9i1.1208 rev i ew art i c l e cardiovascular diseases in natural disasters; a systematic review javad babaie1,2,3, yousef pashaei asl1,4, bahman naghipour5, gholamreza faridaalaee6,7,8∗ 1. department of health policy & management, tabriz university of medical sciences, tabriz, iran. 2. tabriz health services management research center,tabriz university of medical sciences, tabriz, iran. 3. iranian center of excellence in health management, tabriz university of medical sciences, tabriz, iran. 4. department of health services management, school of health management and information sciences, iran university of medical sciences, tehran, iran. 5. department of anaesthesiology and intensive care, tabriz university of medical sciences, tabriz, iran. 6. emergency medicine research team, faculty of medicine, tabriz university of medical sciences, tabriz, iran. 7. department of emergency medicine, maragheh university of medical sciences, maragheh, iran. 8. disaster research team, tabriz university of medical sciences, tabriz, iran. received: march 2021; accepted: march 2021; published online: 4 may 2021 abstract: introduction: as a result of destruction and lack of access to vital infrastructures and mental stress, disasters intensify cardiovascular diseases (cvds) and hence management of cvds becomes more challenging. the aim of this study is investigating incidence and prevalence of cvds, morbidity and mortality of cvds, treatment and management of cvds at the time of natural disasters. methods: in the present systematic review, the articles published in english language until 28. 11. 2020, which studied cvds in natural disasters were included. the inclusion criteria were cvds such as myocardial infarction (mi), acute coronary syndrome (acs), hypertension (htn), pulmonary edema, and heart failure (hf) in natural disasters such as earthquake, flood, storm, hurricane, cyclone, typhoon, and tornado. results: the search led to accessing 4426 non-duplicate records. finally, the data of 104 articles were included in quality appraisal. we managed to find 4, 21 and 79 full text articles, which considered cardiovascular diseases at the time of flood, storm, and earthquake, respectively. conclusion: prevalence of cvd increases after disasters. lack of access to medication or lack of medication adjustment, losing home blood pressure monitor as a result of destruction and physical and mental stress after disasters are of the most significant challenges of controlling and managing cvds. by means of quick establishment of health clinics, quick access to appropriate diagnosis and treatment, providing and access to medication, self-management, and self-care incentives along with appropriate medication and non-medication measures to control stress, we can better manage and control cardiovascular diseases, particularly hypertension. keywords: natural disasters; earthquakes; floods; cardiovascular diseases; hypertension; acute coronary syndrome cite this article as: babaie j, pashaei asl y, naghipour b, faridaalaee gh. cardiovascular diseases in natural disasters; a systematic review. arch acad emerg med. 2021; 9(1): e36. 1. introduction over recent years, the number of disasters and their costs has been increasing and is 6 times higher compared with the first ∗corresponding author: gholamreza faridaalaee; department of emergency medicine, tabriz university of medical sciences, daneshgah street, tabriz, iran. tel: +98-4133829540, email: faridaalaee@tbzmed.ac.ir, grf.aalae@yahoo.com. orcid: https://orcid.org/0000-0002-9990-4936. half of the last century (1-3). for instance, about 324 disasters with 141 million casualties occurred only in 2014 (4). in addition to destroying homes, roads, drinking water system, electricity and gas system, and causing other economic damages, disasters lead to an increase in the incidence of communicable diseases, non-communicable diseases (ncds), and trauma (5). ncds were the leading cause of mortality and morbidity in the world over the last century and their incidence and prevalence have an increasing trend. it is expected that incidence and prevalence of ncds increase at the time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. babaie et al. 2 of disasters and the people present in the disaster area be more vulnerable to ncds (6, 7). cardiovascular diseases (cvds) is the main category of ncds whose incidence and prevalence have an increasing trend due to changing life style and aging population (8-10). ncds leads to 40 million deaths in the world each year and like other ncds, incidence and prevalence of cvds increases after disasters (9). as a result of destruction and lack of access to vital infrastructures such as homes, health centers, medication and also causing physical and mental stress, disasters intensify cvds and hence management of cardiovascular diseases faces a fundamental challenge (10-13). the aim of this systematic review study is investigation of incidence and prevalence of cvds, morbidity and mortality of cvds, and treatment and management of cvds, at the time of natural disasters. 2. methods this is a systematic review based on prisma protocol. in this study, pico is defined as: p, which stands for problem or population, is individuals with cardiovascular diseases, (i) is natural disasters, (c) comparing normal situation, and the (o) outcome is prevalence, treatment, and management of cvds. 2.1. eligibility criteria in the present study, the articles published in english language until 28. 11. 2020, which studied cvds in natural disasters were included. the inclusion criterion was study of cvds such as myocardial infarction (mi), acute coronary syndrome (acs), hypertension (htn), arrhythmia such as atrial fibrillation (af), ventricular tachycardia (vt), ventricular fibrillation (vf), and paroxysmal supraventricular tachycardia (psvt), pulmonary edema, and heart failure (hf) in natural disasters such as earthquake, flood, storm, hurricane, cyclone, typhoon, and tornado. the articles published in the form of abstract as a poster, conference proceeding, commentary, editorial, and case report were excluded. in this study, volcano and climate changes were not included. similarly, man-made disasters were excluded and not reviewed. 2.2. search strategy in order to achieve the purpose of the present study, search items and their related key terms were selected by means of using mesh and emtree databases, consulting with expert specialists, searching the titles and abstracts of the related articles under supervision of a specialist and researcher in emergency medicine and a health management in disasters ph.d. an extensive search in electronic databases including medline, web of science, embase, and scopus until 28. 11. 2020 was done. search strategy in medline database is presented in table 1. 2.3. study selection and data collection process and outcome appraisal in this study, all articles published in english language, which studied cvds in natural disasters, were included. screening of the articles was done based on inclusion and exclusion criteria. first, abstracts of the articles were read by two independent researchers. then, after selecting the eligible articles, full texts of the articles were evaluated. afterwards, the full text was considered in accordance with inclusion and exclusion criteria and eligible articles were selected. summarizing the articles and recording the data in the checklist along with final quality control was performed by two independent individuals. any discrepancy in views was resolved through discussion between two parties or by means of consulting a third researcher. the articles were summarized using a checklist, which has been designed based on prisma statement (14). in this systematic review, outcome appraisal was prevalence, treatment, and management of cvds in natural disasters. data related to first author and year of publication, being peer reviewed, obtaining ethical or publication committee approval, definition of the outcome, expression of exclusion criteria, presence of a control group, and expression of statistical method were extracted. 2.4. statistical analysis data analyses were done in a descriptive way. all the articles were summarized and categorized based on the considered variables. 2.5. ethics since systematic review studies consider the previously published studies and the research is not directly done on human or animal, there is no need for ethical approval. 3. results 3.1. study selection and study characteristics the search led to 4426 non-duplicate records. 4,199 abstracts were excluded as they were not related to the purpose of our study. also, 115 studies were case report, letter to editor or correspondence, review articles, abstracts presented at the conferences and non-english, all of which were excluded from the study. 112 article abstracts were eligible and hence necessary measures to provide their full text were taken. also, six full text articles were studied but since they did not meet our criteria, they were excluded. we were not able to the find full text of two articles. they were not even accessible in the journal archive. finally, the data of 104 articles were included in quality control appraisal. we managed to find 4, 21 and 79 full text articles, which considered cardiovascular diseases at this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e36 the time of flood, storm, and earthquake, respectively. the selection process and prisma diagram are shown in figure 1. due to the variety of our included articles, based on natural disasters, we grouped the included articles into 3 categories including storm (hurricane, typhoon, cyclone and tornadoes), flood, and earthquake. 3.2. quality control of study and risk of bias the included articles were qualitatively considered. the qualitative review results of flood, storm (hurricane, cyclone, typhoon, and tornadoes), and earthquake are presented in table 2, 3, and 4, respectively. 3.3. cvds in flooded areas prevalence of cvds increases after flood. diseases like af, psvt, acs, severe chf, cardiopulmonary arrest, and ami undergo a remarkable increase in the first week and then decrease. the second wave of increase in the number of cvds is also observed in the 7th week (15). existence of negative experiences such as loss of property, physical work, financial problems, alcohol use, and perceived distress in the long run can lead to hypertension (16). nevertheless, some studies indicated that despite the increasing prevalence of cvds after flood, such an increase is not statistically significant (17) and when confounding factors are excluded from the study, increase in the prevalence of cvd is not observed (18). 3.4. cvds in storm area (hurricane, typhoon, cyclone and tornado) prevalence of cvds including htn, ami, and fatality caused by cvds increase after hurricane (19-24). in the areas extremely affected by the hurricane, the rate of cvds, particularly htn, is high (23, 25). unemployment, drug abuse, smoking, temporary housing life, and lack of health insurance are among the risk factors of increase in the prevalence of cvds, particularly ami (20-22, 26). after hurricane, cvds obviously increase in women over 45 years of age; however, in the 6-month follow-up, no increase is observed (27). in terms of circadian and septadian rhythms, studies indicated that within 3 years, and in some studies within 6-10 years, after hurricane, the rate of cvds increased only on the evenings and weekends. however, on the following morning and the first day of the week, a considerable decrease is observed in the prevalence of ami (2, 21, 22). since tornado has a small volume and does not take more than some minutes, it does not cause increase in cardiovascular diseases (28). at the time of evacuation, some patients forget to take their medication out of their home and some of them run out of medication or cannot obtain them and lack of medication makes them unable to control their htn and hence uncontrolled htn increases (29, 30). the issue is so prevalent and 48.4% of those who are taken to shelters lack medication, most of whom are male and have no health insurance (31). also, about 10% of the patients, who are taken to shelter, have chest pain and require emergent treatment (31). after hurricane, adherence to medication regimen decreases, particularly in individuals over 65 years of age and non-whites, (26), which causes more uncontrolled htn in these individuals in comparison with those who have higher adherence to antihypertensive drugs (29). however, after one year and in the second year after hurricane, adherence to medication returns to its previous state (32). the other factor leading to higher and uncontrolled htn is stress (33); particularly in the elderly, it causes an increase in cvds and lack of controlled htn (34, 35). reasons for such stress factors include lower capability of coping with disaster, more damage to living place, stress of living after hurricane, increase in separation from friends and family, fewer visits to friends and family, loss of property and relatives (33). medication request rate is higher in patients with cvds in comparison with other diseases. although only 11% of the complaints belong to the patients with cvds, 52% of the requests for medication are for cvds (36). also, 55.6% of the individuals, who live in shelter, suffer from chronic diseases like htn, diabetes, hypercholesterolemia, pulmonary diseases, and mental disorders (31). the amounts of medication required for chronic diseases and cvds make up a high percentage of the medication required during hurricane, which are 68% and 39%, respectively (37). temporary reduction in access to health care centers leads to a decrease in the number of patients referring for primary care after reopening of the centers and as a result more uncontrolled htn can be observed (28). to improve the quality of health care services, the following points are recommended (30): 1. having electronic health records, which enables the treatment staff to have access to the history of patients, prescribe the previous drugs of the patient appropriately and quickly, and to better control chronic diseases upon emergencies. 2. electronic health records backup. 3. appropriate storage of medications 4. all members of healthcare provider team should be aware of the plan and their own roles, and 5. for times when telephone and internet disconnect, there should be a backup communication system. 6. appropriate relationship between donors and relief teams. since during such disasters, drugs and medical equipment are donated, there is not much assurance as to their being intact and appropriately preserved. even, some of them are unsuitable and inapplicable. hence, those who intend to donate drugs and medical equipment should have a direct relationship with healthcare provider team. 7. selfmanagement of the patients for chronic diseases should be encouraged and reinforced. 8. there should be an effective communication plan between the individuals and healthcare providers. 9. all the stresses should be controlled (30). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. babaie et al. 4 3.5. earthquake so far, numerous earthquakes have occurred. out of these earthquakes, the great east japan earthquake in 2011 with the magnitude of 9 on richter scale was one of the most severe ones, which caused triple disasters (38). in addition to its own causalities, it caused tsunami whose casualties were like those of intense flooding. on the other hand, fukushima daiichi nuclear power plant was damaged, which caused leakage of radioactive materials (38). hence, the studies related to this earthquake will be run in two separate parts: the earthquake, and the surrounding area of the fukushima daiichi nuclear power plant, which was damaged after the great east japan earthquake, is discussed separately. based on the studies performed after the earthquake, prevalence of cvds such as htn, acs, ami, ihd, hf, vf, sustained or nonsustained vt, and cardiomyopathy and other types of mortality increase after the earthquake (39-79). the rate of cvd outbreak in the regions more impacted and more damaged by the earthquake is higher than other areas. fatal mi had a significant increase in high impact areas; however, in low impact areas its rate was not different from that of before the earthquake (80). also, in high impact areas, higher rate of decompensated hf and ami is observed, particularly among women and the elderly and those who had to abandon their home (81, 82). impact of the earthquake on cvds is not permanent and after a period, the incidence rate of cvds returns to its normal state. the earthquake not only has not had any remarkable impact on long-term prognosis in 30 years, but also has not had any midterm impact on cvds in 4 years after earthquake in the affected area (83, 84). some studies indicate that this impact was even less than this and after a few weeks, there was no increase in observed incidence and prevalence of acs and htn (43, 47, 51, 59, 76, 85-89). some studies even express that incidence of cvds in the first week of the earthquake had a remarkable increase and after that this increase is less observed (43, 90). the less severe earthquakes are, the sooner the return to previous state takes place (40, 85). conversely, the more severe earthquakes are, the more damage there will be; hence, the increase in incidence of cvds will last longer and the return to baseline state will occur later; like in sichuan earthquake with the magnitude of 8 on the richter scale, where intense destruction occurred and 5 million people were displaced (43, 44, 62, 91, 92). in new zealand, two earthquakes occurred with an interval of 6 months. the first one was 7.1 on the richter scale and an increase in cvds was observed for 3 weeks. however, in the second one with the magnitude of 6.3 on the richter scale an increase in cvds was observed for 2 weeks (43). in the less intense earthquakes the rate of cvds was significantly high only for 3 days; like the two earthquakes that occurred in thessaloniki, greece, on 19th and 20th of 1978 with the magnitude of 5.2 and 6.4 on the richter scale, respectively (93). the other factor impacting the incidence of cvds is distance from the center of the earthquake. the observed incidence of cvds such as htn was lower among those who lived more than 50 km away from the center of the earthquake (51). blood pressure (bp) increases in the people with chronic diseases such as renal failure (94, 95). other risk factors of increase in bp and uncontrolled bp in the people who live in shelters include being over 55 years old, history of having htn, and having insomnia. hence, in addition to taking their previous medication regularly, they probably need to increase their previous medication (83). the time, at which the earthquake takes place, is another factor affecting the incidence rate of cvds. for instance, loma prieta earthquake, in 1989, took place at 5:04 pm in san francisco. the magnitude of the earthquake was 7 on the richter scale. in comparison with the days before or after the earthquake or in comparison with the same day in 1990, on the day of loma prieta earthquake, there was not any statistically remarkable increase observed in ami admission in san francisco area. northridge, los angeles, earthquake in 1994 occurred at 4:31 am and there was a 110% increase in the rate of ami admission in los angeles on the day of the earthquake in comparison with the mean admission rate over 7 years before the earthquake. sudden death rate also increased. therefore, severe emotional stress resulting from sudden wake-up stress affects the increase in ami. and if there is less stress, ami risk is lower as well (96, 97). in fact, stress plays a pivotal role in increase in incidence of cvds, which mostly happens because of mental stresses such as losing property and relatives (39, 47, 49, 51, 56, 85, 98). also, in some studies, white coat is thought to be one of the factors affecting stress and increasing bp after the earthquake (87). in some other studies, signs of depression at the time of admission remarkably predict the risk of rehospitalization for ihd (44). mental stress resulting from heavy work leads to increase in the incidence of htn after the earthquake. disaster staff, who work in the quaked area, face the risk of increasing htn if they have a heavy workload (99). even, ordinary government employees showed a higher rate of increase in htn in the quaked area. in this study, the average time of monthly extra work of ordinary employees in march, 2011, was 10 times more than public people in the previous march. therefore, after the earthquake blood pressure of government employees should be controlled and if required treatment should be prescribed (75, 100). also, circadian rhythm changes play a role in increasing fatality resulting from cvds, which occurred more in the elderly at night and in the morning, but no increase in fatality was observed between 11 am and 11 pm (101). age, family history of bp, obesity, sleep disorder, waist to hip ratio, high blood sugar, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e36 and high-salt food are other factors that affect the increase in incidence of htn and uncontrolled htn after the earthquake (47, 62, 101, 102). one of the other reasons for uncontrolled blood pressure is discontinuity of antihypertensive drugs, which happens because of various reasons. in the people with psychological problems, the risk of stopping using antihypertensive drugs is higher (103). one of the cases with different results is a study carried out in new zealand. in this study, after two earthquakes, there was no increase observed in ventricular arrhythmia (104). another study expressed that through stimulating sympathetic nerve, earthquake leads to increase in hr and cardiac mortality. however, in the individuals over 60 years of age, stimulation of sympathetic nerve system was blunt (52). in another study, it was said that individuals who lose their residence and live in temporary residence areas, can control their bp as good as the people who live at their own home. however, individuals, particularly the elderly, who live at their own home, indicate increase in bp on winter mornings. similarly, as to the individuals who do not have any changes in their bp medicine, increase in bp was observed, the researcher did not explain the reasons, though (105). 3.6. fukushima area after the great east japan earthquake areas within 20 km of fukushima nuclear power plant were determined as high-risk and restricted areas due to nuclear radiations more than 20 msv per year. almost all of the residents had to evacuate their homes (106, 107). from 20-30 km of the nuclear plant was determined as area prepared for evacuation at the time of emergency. the areas within 30 km of the plant were determined as deliberate evacuation areas (106). incidence of htn, tachycardia, mi, af, and the deaths related to cvds was higher in the individuals who had to abandon their homes (107-113). cvds risk was higher than normal range within 2 years after the incident (111). however, some studies indicated that incidence of ami was higher than the surrounding areas only until one month after the incident (107). other studies held that there was no remarkable difference in the prevalence of ami before and after the earthquake in fukushima area (114). stress is a leading factor in increasing the risk of cvds and hence, a higher rate of cvd is observed in individuals with depression and ptsd (115) and there is a higher increase in the prevalence of cvds because of psychological stresses like losing property, relatives or job (115, 116). other risk factors include: previous cvd, being female, being 40-90 years old, obesity, being alcoholic and having dinner late at night (111, 115, 117). after the earthquake, a higher incidence of af is observed in men compared to other groups (109). in comparison between evacuees and non-evacuees, there was no difference or little difference in term of increase in bp (106). 3.7. special groups in a study on pregnant women, it was indicated that those who were in their 3rd trimester of pregnancy at the time of incident and stress more commonly had pregnancy htn (118). in children under 15years of age, within 1 year of the incident, increase in incidence of htn is observed (119). it has also been reported that within 4 years of the incident, increase in incidence of htn in children is observed. in a study on the impacts of great east japan earthquake on the bp of the injured children, it was indicated that the children who went through more stressful incidents like tsunami waves, corpse of their relatives or friends, fire waves or separation from their parents, higher bp was observed. of these children, those who witnessed fire waves indicated higher diastolic bp (120). 3.8. management of cvds one of the important measures to take in order to decrease the risk of cvds is to strengthen buildings before the earthquake happens. it can be claimed that the less destruction in building, the lower the risk of cvds (42). so as to prevent and treat cvds, controlling stress is another paramount issue that should be taken into account. over this period, decrease in stress and coronary risk factors may decrease mortality resulting from coronary heart disease (chd) after a main eq (48). prescription of tranquilizers and anti-depression medication can help control htn and their prescription may even be essential (121). after crises, it is more likely that patients stop taking drugs, encouraging hypertensive patients to start taking drugs again may help reduce cvd risk (122). after the earthquake, changing the patients’ antihypertensive drugs is another important measure that leads to better control of htn. data show that after earthquake, paying special attention to bp level and treatment modifications can be important not only immediately, but also for some months after the earthquake (70). studies showed that patients who were under treatment of α-blocker or β-blocker or reninangiotensin inhibitor either did not show any change in their bp level or there was little increase (79). supplying a morning home blood pressure measuring device to control morning home blood pressure is essential for preventing cvds’ side effects (123). due to many reasons such as losing morning home blood pressure equipment, damage to other equipment, or anxiety caused by vast destruction, most of the patients were not able to measure morning home blood pressure (123). in patients who lived in a shelter, precise control of bp until 4 years was possible usthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. babaie et al. 6 figure 1: prisma flow diagram. ing an automatic home sphygmomanometer and web-based information and communications technology (icttechnology) (124). controlling bp, nutrition, and personal hygiene can decrease hf as well (102). timely and appropriate intervention is another factor that can help reduce due to cvds. complications like hf can occur less under the condition that patients are immediately admitted for ami and the treatment begins quickly (125). also immediate admission and intervention improves primary function of pci (125). 4. discussion in this systematic review study, incidence and prevalence of cvds, morbidity and mortality of cvds, and treatment and management of cvds, were investigated. prevalence of cvds increases after disasters. this increase directly depends on the intensity of the damage to the disaster area. the most import reason for such an increase are stresses like losing home and relatives and friends, disconnection with friends and relatives, losing job and joblessness, and lack of consistency following the incident. also, high-risk individuals like the elderly are more susceptible. however, using appropriate medication and non-medication measures in terms of stress, it is possible to decrease prevalence of cvds. quick establishment of health clinic and access to appropriate and quick treatment within a few months after disaster is of other measures that can help control cvds. such measures like providing and providing access to medication, consulting to change dose or type of medication, and encouraging selfmanagement and self-care can help decrease these complications to minimum. similarly, it is essential to pay attention to special populations like pregnant women, particularly within their third trimester of pregnancy and children under 15. in a review study, kazuomi kario et al., 2012, studied the effects of 2011 great east japan earthquake and hanshinawaji earthquake on cvds. this study probed into in-clinic and off-clinic htn, potential mechanism of htn in disasters, and management of these diseases. the results indicated that bp increases after earthquake and complications related to lifestyle, like stressful factors such as bad quality of sleep, and complications related to activity, such as lack of physical movement after earthquake, can lead to biological rhythm disorders. aldosterone and cortisone increase in biological rhythm disorders and consequently sympathetic nerve is stimulated, which leads to increase in the use of salt and hence htn. in this study, controlling use of salt along with establishing a quiet sleeping condition, being away from stress, appropriate physical activity, and having self-management to prevent obesity are mentioned as important factors to control htn (126). similarly, in our study, controlling stress, encouraging selfcare and self-management, and providing bp measuring device to facilitate self-care and self-management are taken to be important factors to control htn. but, in the study done by kazumi, providing bp measuring device to facilitate selfcare is not mentioned (126). in 2015 and 2016 a guideline titled disaster medicine for cvd was published by japanese circulation society (12). this guideline includes a number of issues like water and food hygiene, salt and sugar regimen, instructions for healthy sleep and providing sound sleep and, if needed, controlling sleeplessness through medication, treating depression, appropriate psychological support, resorting to appropriate diagnostic methods to control cvds and treat them, and making sure the medication is taken at home to manage and control cvds (12). results of this study as well as the clinical guide is consistent with our study, which accentuates controlling stress and providing sound sleep, following a special diet, providing healthy food to the individuals affected by disaster, prescribing medication for sleeplessness, changing htn medication, controlling risk factors of cvds, and quickly treating newly-admitted patients or the intensified cases already admitted (12). results of the study by errol d et al. are also consistent with our study. that study has also mentioned stress in the disaster area, financial stress resulting from losing job and not having insurance, lack of access to healthy food, salty and high-carbohydrate food, and disconnection with the health system and health service providers as some factors that lead to difficulty in controlling htn during the hurricane (127). the study has recommended some solutions, like having a list (can be electronic) of medications, presenting data rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e36 lated to complications of not using medication (before disaster), having enough supply of medication, providing appropriate access to medication during disaster, and appropriate control of stress (127). in a systematic review study in 2019, farzad gohardehi et al. probed into htn and diabetes after disasters. like our study, they indicated that prevalence of htn remarkably increases after disasters (3). 5. limitations in this study, non-english articles were excluded, which resulted in losing some data. 6. conclusion prevalence of cvds increases after disasters. lack of access to medication or lack of medication adjustment, losing home bp monitor device as a result of destruction, and physical and mental stress after disasters are of the most significant challenges of controlling and managing cvds. by means of quick establishment of health clinic, providing quick access to appropriate diagnosis and treatment, providing access to medication, and self-management and self-care incentives, along with appropriate medication and non-medication measures to control stress, we can better manage and control cardiovascular diseases, particularly hypertension. 7. declarations 7.1. conflict of interest there is no conflict of interest 7.2. acknowledgements all authors thank tabriz university of medical sciences for supporting this study. 7.3. funding and supports there is no funding. 7.4. authors’ contributions yousef pashaei asl, bahman naghipour and gholamreza faridaalaee: abstract reading and data extraction. gholamreza faridaalaee: writingoriginal draft preparation. javad babaei: reviewing and editing. all authors: conceptualization, methodology, and acceptance of final manuscript. references 1. eshghi k, larson rc. disasters: lessons from the past 105 years. disaster prevention and management: an international journal. 2008. 2. peters mn, moscona jc, katz mj, deandrade kb, quevedo hc, tiwari s, et al., editors. natural disasters and myocardial infarction: the six years after hurricane katrina. 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2009 l’aquila earthquake. internal medicine journal. 2013;43(9):1031-4. 56. huang k, deng x, he d, huang d, wu q, wen s, et al. prognostic implication of earthquake-related loss and depressive symptoms in patients with heart failure following the 2008 earthquake in sichuan. clinical cardiology. 2011;34(12):755-60. 57. sofia s, melone a, manzoli l, de ciantis p, varrato e, di filippo r, et al. cardiovascular and cerebrovascular events preand post-earthquake of 6 april 2009: the abruzzo’s experience. am j hypertens. 2012;25(5):556-60. 58. li c, luo x, zhang w, zhou l, wang h, zeng c. yaan earthquake increases blood pressure among hospitalized patients. clinical and experimental hypertension (new york, ny : 1993). 2016;38(6):495-9. 59. trevisan m, jossa f, farinaro e, krogh v, panico s, giumetti d, et al. earthquake and coronary heart disease risk factors: a longitudinal study. am j epidemiol. 1992;135(6):632-7. 60. takegami m, miyamoto y, yasuda s, nakai m, nishimura k, ogawa h, et al. 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experimental hypertension. 2006;28(8):719-29. 124. nishizawa m, hoshide s, okawara y, matsuo t, kario k. strict blood pressure control achieved using an ict-based home blood pressure monitoring system in a catastrophically damaged area after a disaster. the journal of clinical hypertension. 2017;19(1):26-9. 125. hao k, takahashi j, ito k, miyata s, sakata y, nihei t, et al. emergency care of acute myocardial infarction and the great east japan earthquake disaster–report from the miyagi ami registry study–. circulation journal. 2014:cj-13-1286. 126. kario k. disaster hypertension–its characteristics, mechanism, and management–. circulation journal. 2012;76(3):553-62. 127. crook ed, arrieta mi, foreman rd. management of hypertension following hurricane katrina: a review of issues in management of chronic health conditions following a disaster. current cardiovascular risk reports. 2010;4(3):195-201. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e36 table 1: medline search strategy database search terms medline (pubmed) 1) “cardiovascular diseases”[mesh] or “pulmonary edema”[mesh] or “hypertension”[mesh] or “acute coronary syndrome”[mesh] or “myocardial ischemia”[mesh] or “coronary disease”[mesh] or “congestive heart failure”[mesh] or “coronary diseases”[tiab] or “myocardial ischemias”[tiab] or “ischemic heart diseases”[tiab] or “ischemic heart disease”[tiab] or “chronic heart diseases”[tiab] or “chronic heart diseases”[tiab] or “hypertension”[tiab] or “high blood pressure”[tiab] or “high blood pressures”[tiab] or “acute coronary syndrome”[tiab] or “acute coronary syndromes”[tiab] or “coronary artery disease”[tiab] or “cardiac disease”[tiab] or “congestive heart failure”[tiab] or “pulmonary edema”[tiab] or “pulmonary edemas”[tiab] “myocardial ischemia”[tiab] or “cardiovascular disease”[tiab] or “cardiac disease”[tiab] or “cardiac diseases” or “cardiac disorder”[tiab] 2) “earthquake”[mesh] or ”floods”[mesh] or ”cyclonic storms”[mesh] or ”tornadoes”[mesh] or ”natural disasters”[mesh] or ”disasters”[mesh] or “earthquake” [tiab] or “catastrophic flooding” [tiab] or “catastrophic flooding”[tiab] or “floods”[tiab] or “cyclonic storms”[tiab] or “cyclonic storm”[tiab] or “cyclone”[tiab] or “cyclones”[tiab] or “hurricanes”[tiab] or “hurricane”[tiab] or “tropical storm”[tiab] or “tropical storms”[tiab] or “typhoons”[tiab] or “typhoon”[tiab] or “tornadoes”[tiab] or “tornado”[tiab] or “tornados”[tiab] or “catastrophic”[tiab] or “natural disasters”[tiab] or “natural disaster”[tiab] 3) 1 &2 table 2: quality assessment and risk of bias in flood high risk of bias: × james n. jana yasuhiro alain low risk of bias: p logue 1980 obrová 2014 nagayoshi 2015 vanasse 2016 publication in peer-review journal p p p p description of patient group p p p p description of control group p p p p ethics approval × × × p informed consent × × × × specified main outcome p p p p specified secondary outcome p p p p description of statistical analysis p p p p conflict of interest status × × × × this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. babaie et al. 14 table 3: quality assessment and risk of bias in storm first author and publication year storm name and event year type of study publication in peerreview journal description of patient group exclusion criteria ethics approval mentioned type of study specified main outcome description of statistical analysis conflict of interest status lisa a. hendrickson 1997 hurricane iniki 1992 c.s p p p × × p p × michael a. jhung 2007 hurricane katrina 2005 c.s p p × × × p × × erica howe 2008 hurricane katrina 2005 c.s p p × p p p p × p. gregg greenough 2008 hurricane katrina 2005 c.s p p × p p p p p ma krouselwood 2008 hurricane katrina 2005 c.s p p p × p p p × t islam 2008 hurricane katrina 2005 co p p p p p p p × sandeep gautam 2009 hurricane katrina 2005 o p p p p p p p p martha i. arrieta 2009 hurricane katrina 2005 q p p × × p p p p erin stanley 2011 hurricane katrina 2005 c.s p p p × p p p × nathan mckinney 2011 4 florida hurricane 2004 c.s p p × × × p p × zhen jiao 2012 hurricane katrina 2005 co p p p × p p p × matthew n. peters 2013 hurricane katrina 2005 co p p p p p p p p matthew n. peters 2014 hurricane katrina 2005 co p p p × p p p p joel n. swerde 2014 hurricane sandy 2012 c.s p p p p × p p × federico silva palacios 2015 tornado in joplin 2011 c.s p p × × × p p × linda meta mobula 2016 typhoon haiyan 2013 o p p × p p p p × aaron baum 2019 hurricane sandy 2012 co p p p p p p p p john c. moscona 2019 hurricane katrina 2005 co p p p p p p p × zachary lenane 2019 hurricane katrina 2005 co p p × p p p p p ninon a. becquart 2019 hurricane katrina 2005 c.s p p × × × p p p hsin-i shih 2020 typhoon morakot 2009 c.c p p × p p p p c.c= case-control, co= cohort study, c.s= cross sectional study, o= observational study, q=qualitative study high risk of bias: ×, low risk of bias: p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2021; 9(1): e36 table 4: quality assessment and risk of bias in earthquake first author and year of publication name of earthquake and year of event type of study publication in peer-review journal description of patient group description of control group exclusion criteria ethics approval specified main outcome description of statistical analysis conflict of interest status kleakatsouyanni 1986 greece 1978 c.s p p ? p × p p × mauriziotrevisan 1986 italy 1980 lo p p p p × p p × mauriziotrevisan 1992 italy 1980 lo p p ? × × p p × annette j dobson 1991 newcastle 1987 c.s p p ? p × p p × jonathan leor 1996 northridge 1994 c.s p p ? p × p p × komei saito 1997 hanshin-awaji 1995 ob p p p p × p p × robert a. kloner 1997 northridge 1994 c.s p p p × × p p × shunji suzuki 1997 hanshinawaji 1995 ob p p ? × × p p × junichi minnmi 1997 hanshinawaji 1995 c.s p p × × × p p × kazuomi kario 1997 hanshinawaji 1995 c.s p p × × p p p × kazuomi kario 1997 hanshin-awaji 1995 c.s p p p p × p p × haroutune k. armenian 1998 armenia 1988 co p p p × × p p × david l. brown 1999 loma prieta 1989 northridge 1994 c.s p p p p × p p × susanh.bland 2000 italy 1983-4 co p p ? × × p p × keiko ogawa 2000 hanshinawaji 1995 c.s p p ? × × p p × kazuomi kario 2001 hanshin-awaji 1995 ob p p ? p × p p × lian-yu lin 2001 taiwan 1999 ob p p p p × p p × kyuzi kamoi 2006 niigata, japan 2004 ob p p ? × × p p × masahito sato 2006 mid-niigata 2004 c.s p p ? × × p p × yucheng chen 2009 sichuan 2008 c.d p p ? × p p p p xiao qiang zhang 2009 sichuan 2008 c.s p p p × p p p p masayuki tsuchida 2009 noto peninsula 2007 ob p p ? × × p p × i nakagawa 2009 niigata chuetsu 2004 c.s p p p × p p p p tomoko azuma 2010 mid-niigata 2004 ob p p p p × p p p kaisen huang 2011 sichuan 2008 co p p p p p p p p huang kai-sen 2011 sichuan 200 co p p ? p p p p × simona sofia 2012 l’aquila 2009 c.s p p p × p p p p makoto nakano 2012 great east japan 2011 c.s p p ? × × p p × motoyuki nakamura 2012 great east japan 2011 ob p p p p p p p × tatsuo aoki 2012 great east japan 2011 c.s p p p p p p p p kenichi tanaka 2012 great east japan 2011 ob p p ? p p p p p tatsuo aoki 2013 great east japan 2011 c.s p p ? × p p p × satoshi konno 2013 great east japan 2011 co p p p × p p p p paolo giorgini 2013 l’aquila 2009 ob p p p p × p p p l. petrazzi 2013 l’aquila 2009 c.s p p ? × × p p p christina chan 2013 christchurch 2010, 2011 c.s p p p p p p p × hitoshi murakami 2013 great east japan 2011 c.s p p p p p p p p akihiro nakamura 2013 great east japan 2011 ob p p p p p p p p eiji nozaki 2013 great east japan 2011 c.s p p ? × p p p × hiroyuki yamauchi 2013 great east japan 2011 ob ? p p p p p kimio watanabe 2013 great east japan 2011 ob p p ? p × p p p x.-c. sun 2013 sichuan 2008 c.s p p ? × × p p × christina chan 2014 christchurch 2010 co p p ? × p p p p takayoshi yamaki 2014 great east japan 2011 c.s p p ? × p p p × tomonori itoh 2014 great east japan 2011 ob p p p × p p p p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. babaie et al. 16 table 4: quality assessment and risk of bias in earthquake first author and year of publication name of earthquake and year of event type of study publication in peer-review journal description of patient group description of control group exclusion criteria ethics approval specified main outcome description of statistical analysis conflict of interest status yoshihiro tani 2014 great east japan 2011 c.s p p p p p p p p kenichi tanaka 2014 great east japan 2011 ob p p ? p p p p × akihiro nakamura 2014 great east japan 2011 c.s p p p × p p p p kiyotaka hao 2014 * great east japan 2011 rct p p p × p p p p fumitaka tanaka 2015 great east japan 2011 ob p p p p p p p × yukihiko kawasaki 2014 great east japan 2011 ob p p p × × p p p masanobu niiyama 2014 great east japan 2011 c.s p p p p p p p × masafumi nishizawa 2015 great east japan 2011 co p p p × × p p p misa takegami 2015 hanshin-awaji 1994 and great east japan 2011 c.s p p ? p p p p p hitoshi suzuki 2015 great east japan 2011 c.s p p p × p p p p yukihiko kawasaki 2015 great east japan 2011 ob p p p p p p p p reiichiro tanaka 2016 great east japan 2011 c.s p p ? p p p p p kaisen huang 2016 sichuan 2008 c.s p p p × × p p × chuanwei li 2016 sichuan 2008 ob p p ? p p p p p tetsuya ohira 2016 great east japan 2011 co p p p p p p p × motoyuki nakamura 2016 great east japan 2011 co p p × × p p p p na li 2017 tangshan 1976 ob p p p p p p p p naoki nakaya 2017 great east japan 2011 c.s p p ? × p p p p masafumi nishizawa 2017 great east japan 2011 co p p × × p p × p motoyuki nakamura 2017 great east japan 2011 ob p p p × p p p p satoshi miyata 2017 great east japan 2011 co p p p p p p p p tetsuya ohira 2017 great east japan 2011 ob p p p × × p p p andrea m teng 2017 christchurch 2010, 2011, 7.1 , 6.3 co p p p p p p p × satoshi konno 2017 great east japan 2011 co p p × × p p p p wen zhang 2017 great east japan 2011 c.s p p ? × p p p p masato nagai 2018 great east japan 2011 co p p p p p p p p christina chan 2019 christchurch 2010, 2011, 7.1 , 6.3 ob p p ? × p p p × mai takiguchi 2019 great east japan 2011 co p p p p p p p p satoshi hoshide 2019 great east japan 2011 ob p p ? × p p p × masahiro watanabe 2019 great east japan 2011 co p p p × p p p p masafumi nishizawa 2019 great east japan 2011, ob p p p × p p p p mimang tembe 2019 nepal 2015, c.s p p ? × p p p × hyo kyozuka 2020 great east japan 2011, ob p p ? p p p p p toshiki sanoh 2020 great east japan 2011 ob p p ? p p p p p c.c= case-control, co= cohort study, c.s= cross sectional study, lo= longitudinal o= observational study, q=qualitative study, randomized clinical trial= rct. * only 1 rct exist, high risk of bias: ×, low risk of bias: p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e45 or i g i n a l re s e a rc h electrocardiographic findings and in-hospital mortality of covid-19 patients; a retrospective cohort study mohammad haji aghajani1,2, amirmohammad toloui3, moazzameh aghamohammadi1,2, asma pourhoseingholi1, niloufar taherpour1, mohammad sistanizad1,4, arian madani neishaboori3, ziba asadpoordezaki5,6,7, reza miri1,2∗ 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of cardiology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. physiology research center, iran university of medical sciences, tehran, iran. 4. department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 5. department of psychology, maynooth university, kildare, ireland. 6. kathleen lonsdale institute for human health research, maynooth university, kildare, ireland. 7. imam-hussein medical and educational centre, shahid beheshti university of medical sciences, tehran, iran. received: april 2021; accepted: may 2021; published online: 12 june 2021 abstract: introduction: although current evidence points to the possible prognostic value of electrocardiographic (ecg) findings for in-hospital mortality of covid-19 patients, most of these studies have been performed on a small sample size. in this study, our aim was to investigate the ecg changes as prognostic indicators of in-hospital mortality. methods: in a retrospective cohort study, the findings of the first and the second ecgs of covid-19 patients were extracted and changes in the ecgs were examined. any abnormal finding in the second ecg that wasn’t present in the initial ecg at the time of admission was defined as an ecg change. ecgs were interpreted by a cardiologist and the prognostic value of abnormal ecg findings for in-hospital mortality of covid-19 patients was evaluated using multivariate analysis and the report of the relative risk (rr). results: data of the ecgs recorded at the time of admission were extracted from the files of 893 patients; likewise, the second ecgs could be extracted from the records of 328 patients who had an initial ecg. the presence of sinus tachycardia (rr = 2.342; p <0.001), supraventricular arrhythmia (rr = 1.688; p = 0.001), ventricular arrhythmia (rr = 1.854; p = 0.011), interventricular conduction delays (rr = 1.608; p = 0.009), and abnormal r wave progression (rr = 1.766; p = 0.001) at the time of admission were independent prognostic factors for in-hospital mortality. in the second ecg, sinus tachycardia (rr = 2.222; p <0.001), supraventricular arrhythmia (rr = 1.632; p <0.001), abnormal r wave progression (rr = 2.151; p = 0.009), and abnormal t wave (rr = 1.590; p = 0.001) were also independent prognostic factors of in-hospital mortality. moreover, by comparing the first and the second ecgs, it was found that the incidence of supraventricular arrhythmia (rr = 1.973; p = 0.005) and st segment elevation/depression (rr = 2.296; p <0.001) during hospitalization (ecg novel changes) are two independent prognostic factors of in-hospital mortality in covid-19 patients. conclusion: due to the fact that using electrocardiographic data is easy and accessible and it is easy to continuously monitor patients with this tool, ecgs can be useful in identifying high-risk covid-19 patients for mortality. keywords: electrocardiography; prognosis; hospital mortality; covid-19 cite this article as: haji aghajani m, toloui a, aghamohammadi m, pourhoseingholi a, taherpour n, sistanizad m, madani neishaboori a, asadpoordezaki z, miri r. electrocardiographic findings and in-hospital mortality of covid-19 patients; a retrospective cohort study. arch acad emerg med. 2021; 9(1): e45. https://doi.org/10.22037/aaem.v9i1.1250. ∗corresponding author: reza miri; department of cardiology, imam hossein hospital, madani st., tehran, iran. phone/fax: +982173432383/77582733, email: miri.reza@yahoo.com, orcid: https://orcid.org/0000-0002-8568-9948. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 2 1. introduction covid-19 is the name of a disease, caused by the novel "severe acute respiratory syndrome coronavirus 2", which appeared in december 2019 in wuhan, china. since the announcement of the global pandemic of covid-19 until december 13, 2020, the number of infected people has exceeded 70 million cases and the death toll has exceeded 1.5 million people worldwide, according to the world health organization (1). overall, covid-19 can cause a range of symptoms in different patients, from a mild to a severe and fatal disease (2). there are studies demonstrating that covid-19 is a multifactorial disease, affecting not only the lungs, but also the central nervous system, the cardiovascular system, and even the blood circulation system (3-6). the available clinical evidence suggests that current treatments are mostly symptomatic, and no definitive cure is yet available. the efficacy of current antiviral and nonsteroidal anti-inflammatory drugs is still questionable (7-9). since there is no definitive cure available for covid-19, it may be possible to manage and monitor high-risk patients more accurately, and commence critical care by observing the red flags in patients from the beginning of disease. several factors have been proposed for predicting the outcome of covid-19 patients. current findings indicate that older age and the presence of comorbidities such as hypertension, diabetes, and cardiovascular diseases are associated with covid-19 severity, and the highest mortality rates have been observed in these groups of patients (10). heart failure and cardiac arrest are among the most common causes of death in covid-19 patients (11). arrhythmias and electrocardiographic changes, both due to the administered drugs and as direct effects of the virus, have also been reported (12, 13). in general, ecg is a very useful tool in diagnosing a variety of cardiac disorders. in most cases, electrocardiograms help in diagnosis of myocarditis, arrhythmias and heart failure (14). due to changes in heart’s electrical activity in most cardiovascular diseases and its diagnostic value in cardiac damage, and since heart’s damage in the course of covid-19 is associated with a high mortality rate, the assessment of ecg changes could be used in determining disease prognosis and management of patients (15). although several studies have been performed to evaluate the prognostic value of electrocardiographic findings for mortality of covid-19 patients, most of these studies have a small sample size and they only assess the relationship between electrocardiographic findings at the time of admission and patients’ overall mortality (12). nonetheless, the effect of electrocardiographic changes during hospitalization on patients’ in-hospital mortality is not clear. given the facts above, our aim in this study was to assess the value of changes in patients’ ecgs as prognostic indicators of in-hospital mortality based on a study with large sample size. 2. methods 2.1. study design and setting the present retrospective cohort study was performed on the records of patients who were admitted to imam-hossein hospital in tehran, between 18 february and 10 july 2020. the present study was approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.retech.rec.1399.681) and the researchers adhered to the principles of the helsinki convention. 2.2. subjects all patients with covid-19 who had at least one ecg during their hospital stay were included in this study. covid-19 infection was confirmed by a positive rt-pcr (polymerase chain reaction) test for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) from a nasopharyngeal specimen (nasopharynx). exclusion criteria were patients without sufficient information in their hospital records, patients without a recorded discharge status (dead or alive) or patients with known ecg abnormalities. 2.3. data collection baseline and demographic variables of patients were extracted from the hospital’s patient registration system. a total of 893 patients had at least one ecg during hospitalization and more evaluation of these records revealed that 328 patients had also a second ecg. ecgs were interpreted by a cardiologist, and to ensure data accuracy, ecgs were randomly re-examined by a senior cardiology attending. the findings of the first and the second ecgs were reviewed separately and recorded in the statistical program. if an abnormal finding was repeated in at least two leads, it was included in the study as a definite abnormal finding. all ecgs were recorded by a 12 standard-lead electrocardiography tool. electrocardiographic findings were sinus tachycardia, sinus bradycardia, supraventricular arrhythmia, ventricular arrhythmia, right bundle branch block (rbbb), left bundle branch block (lbbb), incomplete rbbb, incomplete lbbb, left anterior hemi-block, posterior interventricular conduction delay (ivcd), bifascicular block, abnormal r wave progression in precordial leads, presence of q wave, prolonged qt interval, st segment abnormalities, and abnormal t wave. to evaluate ecg changes, any abnormal finding in the second ecg that wasn’t present in the initial one at the time of admission was defined as a change in the ecg; accordingly, abnormal findings were defined as any changes in the waves’ shape or differences in length or timing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e45 of the normal components of an ecg. 2.4. statistical analysis continuous variables were described as mean ± standard deviation (sd), and categorical variables were expressed as counts (percentage). we have examined normality assumption by checking kurtosis, skewness, box plot and q-q plot. t-test and mann–whitney u test were used for comparisons of means of variables in alive and dead patients. besides, for evaluating the association between categorical variables, chi-square test and fisher’s exact test were used. in addition, a multivariate logistic regression model was performed for investigating the association of electrocardiographic findings and in-hospital mortality of covid-19 patients. to avoid over-fitting in the multivariate model, only factors which had a p-value less than 0.1 in univariate analysis were selected for the multivariate model. final model was selected according to backward wald logistic regression. the findings were reported as odds ratio (or) and 95% confidence interval (95% ci). two-side p-value less than 0.05 was considered statistically significant. all analyses were done using statistical package for the social sciences (spss) 24.0. 3. results 3.1. baseline characteristics the data of 893 ecgs at the time of admission was documented in patients’ records and could be extracted; of these, 494 patients were male (55.3%). the mean age of patients was 61.8±17.2 years (range: 10-99 years). the duration of hospitalization varied between 1 and 80 days (mean ± sd: 7.9 ± 6.8 days). 107 patients (12%) were admitted to the icu and 231 patients (25.9%) finally passed away (table 1). 3.2. first ecg and in-hospital mortality according to the patients’ records, 893 patients had an interpretable ecg at the time of admission. examination of these ecgs showed that the most common abnormal findings in the ecg of covid-19 patients at the time of admission were sinus tachycardia (35.5%), abnormal t wave (24.7%), st segment depression (19.1%), and prolonged qt interval (18.2%), bi-fascicular block (17.2%), and left anterior hemi-block (13.2%). univariate analyses showed that age (p <0.001), sinus tachycardia (p <0.001), sinus bradycardia (p = 0.022), supraventricular (p <0.001) and ventricular (p = 0.037) arrhythmias, ivcd (p = 0.007), abnormal r wave progression in peri-cordial leads (p = 0.002), st segment elevation / depression (p = 0.002), and abnormal t wave (p = 0.023) had a significant correlation with in-hospital mortality of covid19 patients (table 1). multivariate analysis showed that increasing age (rr = 1.036, 95% ci: 1.029, 1.044; p <0.001) is one of the prognostic factors of in-hospital mortality in covid-19 patients. additionally, sinus tachycardia (rr = 2.342; 95% ci: 1.250, 2.280; p <0.001), supraventricular arrhythmia (rr = 1.688; 95% ci: 1.250, 2.280; p = 0.001), ventricular arrhythmia (rr = 1.854; 95 % ci: 1.154, 2.979; p = 0.011), ivcd (rr = 1.608; 95% ci: 1.129, 2.291; p = 0.009), and abnormal r wave progression (rr = 1.766; 95% ci: 1.260, 2.474; p = 0.001) in the initial ecg at the time of admission were independent prognostic factors of in-hospital mortality (table 2). 3.3. second ecg and in-hospital mortality examination of patients’ records showed that 328 patients underwent a second ecg examination during their hospital stay. the most common abnormal findings on the second ecgs were abnormal t wave (31.1%), sinus tachycardia (30.5%), st segment depression (22.6%), prolonged qt interval (20.1%), bifascicular block (16.1). %), supraventricular arrhythmia (11.9%), left anterior hemi-block (11.3%), and sinus bradycardia (10.7%). univariate analyses illustrated that the presence of sinus tachycardia (p = 0.001), sinus bradycardia (p = 0.011), supraventricular arrhythmia (p <0.001), st segment elevation / depression (p = 0.037), and abnormal t wave (p = 0.003) in the second ecg of patients had a significant correlation with their in-hospital mortality. moreover, the correlation between mortality of patients and the presence of ivcd (p = 0.065) and abnormal r wave progression in peri-cordial leads (p = 0.059) in the second ecg was also close to the significance level (table 3). multivariate analysis showed that older age (rr = 1.022, 95% ci: 1.014, 1.031; p <0.001) is still one of the independent prognostic factors of in-hospital mortality in covid-19 patients. likewise, the presence of sinus tachycardia (rr = 2.222; 95% ci: 1.597, 3.091; p <0.001), supraventricular arrhythmia (rr = 1.632; 95% ci: 1.792, 3.866; p <0.001), abnormal r wave progression (rr = 2.151) 95% ci: 1.206, 3.834; p = 0.009), and abnormal t wave (rr = 1.590; 95% ci: 1.221, 2.069; p = 0.001) in the second ecg were independent prognostic factors of inhospital mortality (table 4). electrocardiographic changes during hospitalization and in-hospital mortality data of 328 patients were analysed in this section. by comparing the second ecg with the ecg at the time of admission, it was found that the most common changes in electrocardiograms during hospitalization were sinus tachycardia (11.5%), prolonged qt interval (9.0%), sinus bradycardia (6.7%), st segment elevation/depression (4.3%), abnormal t wave (4.0%), supraventricular arrhythmia (4.0%), and ventricular arrhythmia (3.4%), respectively. univariate analyses showed that the incidence of supraventricular arrhythmia (p = 0.029) and st segment elevation/depression (p=0.006) during hospitalization has a strong correlation with patients’ inhospital mortality (table 5). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 4 moreover, multivariate analysis showed that supraventricular arrhythmia (rr = 1.973; 95% ci: 1.234, 3.154; p = 0.005) and st segment elevation/depression (rr = 2.296; 95% ci: 1.574, 3.349; p < 0.001) during hospitalization, were two independent prognostic factors of in-hospital mortality in covid-19 patients (table 6). 4. discussion this retrospective cohort is one of the few studies with a large sample size, which investigates the prognostic value of covid-19 patients’ ecg findings in predicting their inhospital mortality. the findings of the present study disclosed that abnormal changes in the ecg, both at the time of admission and during hospital stay can be used for predicting disease prognosis. the analyses were performed in three sections. in the first part, the relationship between electrocardiographic findings at the time of admission and inhospital mortality of covid-19 patients was studied. in the second part, the relationship between in-hospital mortality and abnormal findings in the second ecg of patients during hospitalization was investigated. finally, the relationship between the in-hospital mortality of covid-19 patients and the changes that occurred between the first and the second ecg was investigated. an interesting point obtained from all three sections of the analysis is the proof of the prognostic role of supraventricular arrhythmia in predicting in-hospital mortality of covid-19 patients. it was also found that the presence of sinus tachycardia and abnormal r wave progression in precordial leads, both in the first and the second ecg of patients has a significant independent relationship with in-hospital mortality in covid-19 patients. finally, the presence of abnormal t wave in the second ecg or st segment elevation/depression during hospitalization is a prognostic factor for mortality of covid-19 patients. in the present study, supraventricular arrhythmia consisted of atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. in all three parts of analysis, it was found that supraventricular arrhythmia has a significant and independent relationship with mortality in patients with covid-19. numerous studies have shown that the occurrence of supraventricular arrhythmias, especially atrial fibrillation, increases the risk of stroke, heart attack, heart failure, and sudden cardiac death by increasing the risk of thrombosis. to be further illustrated, sudden cardiac death is the most common cause of cardiac death in patients with atrial fibrillation (16). in a situation with increased pressure on the cardiovascular system, due to hyperactivity of the immune system or infection, the occurrence of atrial arrhythmias with a risk of thrombosis, increases the risk of fatal cardiovascular events; and it must be taken into consideration that covid-19 itself, especially in its severe forms, also rigorously increases the risk of thrombosis (17). moreover, the risk of complications from atrial fibrillation such as stroke and thrombosis increase in the setting of other underlying diseases such as dyslipidaemia and diabetes, which have also been shown to be associated with more severe covid-19 (18). there are other studies that show the association of other types of supraventricular arrhythmias, such as premature atrial contraction, with patient mortality (19). the occurrence of abnormal r wave progression in the precordial leads can point to 4 different causes: anterior myocardial infarction, left ventricular hypertrophy, right ventricular hypertrophy, and a natural variant in people whose anterior cardiac forces are weaker than others. abnormal r wave progression is expected to be more frequently detected in severe covid-19; since in most cases, more severe covid-19 usually occurs in the presence of other comorbidities such as diabetes and coronary heart disease, and these underlying diseases themselves could cause abnormal r wave progression (20, 21). considering the fact that abnormal r wave progression is an independent prognostic factor in predicting patients’ in-hospital mortality, the emergence of this finding in patients’ ecgs could warn physicians of the need for more accurate patient management. sinus tachycardia is common in patients with severe medical conditions and is significantly associated with covid-19 patients’ mortality. a patient with severe covid-19 may develop sinus tachycardia due to fever, systemic inflammation, shortness of breath, hypoxia, and dehydration. the presence of untreated sinus tachycardia can lead to ischemia of the heart, decreased cardiac output, cardiomyopathy, cardiac arrest, and death (22, 23). therefore, sinus tachycardia seems to be a warning sign that the patient’s condition could be getting worse and the patient is developing a more severe form of covid-19; accordingly, sinus tachycardia can be used as an indicator in management of covid-19 patients. abnormal t wave was another finding that was directly related to in-hospital mortality of covid-19 patients. t wave inversion has been reported in 27% of patients with myocarditis and this t-wave was associated with cardiac edema in the corresponding position on cardiac mri (24). nonetheless, in delayed contrast enhancement imaging, performed to examine cardiac fibrosis, no correlation with t wave inversion was observed, which suggests its emergence in the acute phase of myocarditis and cardiac edema (25). therefore, it seems that the presence of abnormal t wave in patients with covid-19 may be due to acute myocardial injury as a result of the virus directly attacking the heart tissue, which could seriously affect the outcome of disease. more comprehensive studies are needed to prove this hypothesis. the analyses of the present study showed that the occurrence of st segment elevation/depression during hospital stay in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e45 a patient who had a normal st segment at the time of admission, could be an alarm sign of their poor prognosis. the occurrence of st segment elevation/depression during hospitalization can be due to virus’ direct attack to myocardial tissue, side effects of therapeutic agents used for patients, or an indicator of myocardial ischemia (26). this study, like other retrospective studies, had its limitations. first, due to the recent pandemic, access to patients’ previous ecgs taken before the onset of covid-19 was not possible and they were not included in this study. second, other diagnostic tools such as echocardiography and laboratory tests were not used along with the ecg, as a result, the prognostic value of ecg may be over or underestimated. moreover, due to the short follow-up period of patients (only during hospitalization), some of the changes that occurred after the second ecg were not included in this study. 5. conclusion the findings of the present study showed that abnormal changes in ecg, both at the time of admission and during hospitalization, can be very useful in predicting the prognosis of covid-19. supraventricular arrhythmia, sinus tachycardia, and abnormal r wave progression in precordial leads, in both of patients’ ecgs had a significant independent relationship with in-hospital mortality. abnormal t wave in the second ecg or the presence of st-segment elevation/depression during hospitalization can have a good prognostic role in predicting the mortality of covid-19 patients. therefore, considering the fact that measuring the electrical activity of heart is a cheap and accessible method and it is easy to continuously monitor patients with this tool, ecgs can be useful in identifying high-risk covid-19 patients and giving them more medical care. 6. declarations 6.1. acknowledgments the authors would like to thank the icu and ccu medical and nursing personnel of imam hossein hospital, shahid beheshti university of medical sciences; dr. ainaz samadi, dr. amir heydari, dr. fatemeh nasiri, dr. mahboubeh ghazanfarabadi, faezeh nesaei, faezeh fakour, ghazaleh amanabadi, ghodsi najjari, golnoush mortezaei, maedeh sayyad, and vida torabi who participated in this project and helped us in performing this project. 6.2. funding and support this research has been supported and funded by shahid beheshti university of medical sciences. 6.3. author contribution study design: rm, mha data gathering: mha, ma, ap, nt, ms, za data analysis: rm, ap interpreting the findings: all authors manuscript writing: all authors 6.4. conflict of interest the authors declare no conflict of interests. references 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multicenter study. journal of geriatric cardiology: jgc. 2019;16(8):630. 15. shafi am, shaikh sa, shirke mm, iddawela s, harky a. cardiac manifestations in covid-19 patients—a systematic review. journal of cardiac surgery. 2020;35(8):1988-2008. 16. eisen a, ruff ct, braunwald e, nordio f, corbalán r, dalby a, et al. sudden cardiac death in patients with atrial fibrillation: insights from the engage af-timi 48 trial. journal of the american heart association. 2016;5(7):e003735. 17. stefely ja, christensen bb, gogakos t, cone sullivan jk, montgomery gg, barranco jp, et al. marked factor v activity elevation in severe covid-19 is associated with venous thromboembolism. american journal of hematology. 2020;95(12):1522-30. 18. violi f, pastori d, pignatelli p. mechanisms and management of thrombo-embolism in atrial fibrillation. journal of atrial fibrillation. 2014;7(3). 19. huang bt, huang fy, peng y, liao yb, chen f, xia tl, et al. relation of premature atrial complexes with stroke and death: systematic review and meta-analysis. clinical cardiology. 2017;40(11):962-9. 20. anttila i, nikus k, lehtimaki t, kahonen m. relation of poor r-wave progression to risk of cardiovascular mortality. european heart journal. 2013;34(suppl_1). 21. zema mj, kligfield p. ecg poor r-wave progression: review and synthesis. archives of internal medicine. 1982;142(6):1145-8. 22. gopinathannair r, olshansky b. management of tachycardia. f1000prime reports. 2015;7. 23. henning a, krawiec c. sinus tachycardia. statpearls [internet]: statpearls publishing; 2020. 24. de lazzari m, zorzi a, baritussio a, siciliano m, migliore f, susana a, et al. relationship between t-wave inversion and transmural myocardial edema as evidenced by cardiac magnetic resonance in patients with clinically suspected acute myocarditis: clinical and prognostic implications. journal of electrocardiology. 2016;49(4):587-95. 25. di bella g, florian a, oreto l, napolitano c, todaro mc, donato r, et al. electrocardiographic findings and myocardial damage in acute myocarditis detected by cardiac magnetic resonance. clinical research in cardiology. 2012;101(8):617-24. 26. zhang x-l, li z-m, ye j-t, lu j, ye ll, zhang c-x, et al. pharmacological and cardiovascular perspectives on the treatment of covid-19 with chloroquine derivatives. acta pharmacologica sinica. 2020;41(11):1377-86. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e45 table 1: baseline characteristics and first electrocardiographic (ecg) findings of covid-19 patients variable alive (n=662) dead (n=231) total (n=893) p age (year; mean ± sd) 58.4±16.9 71.4±13.9 61.8±17.2 <0.001 sex women 307 (46.4) 92 (39.8) 399 (44.7) 0.85 men 355 (53.6) 139 (60.2) 494 (55.3) ecg findings sinus tachycardia no 449 (67.8) 127 (55.0) 576 (64.5) <0.001 yes 213 (32.2) 104 (45.0) 317 (35.5) sinus bradycardia no 614 (92.7) 224 (97.0) 838 (93.8) 0.022 yes 48 (7.3) 7 (3.0) 55 (6.2) supraventricular arrhythmia* no 616 (93.1) 189 (81.8) 805 (90.1) <0.001 yes 46 (6.9) 42 (18.2) 88 (9.9) ventricular arrhythmia# no 646 (97.6) 219 (94.8) 865 (96.9) 0.037 yes 16 (2.4) 12 (5.2) 28 (3.1) rbbb no 633 (95.6) 219 (94.8) 852 (95.4) 0.611 yes 29 (4.4) 12 (5.2) 41 (4.6) lbbb no 644 (97.3) 223 (96.5) 867 (97.1) 0.562 yes 18 (2.7) 8 (3.5) 26 (2.9) incomplete rbbb no 643 (97.1) 225 (97.4) 868 (97.2) 0.829 yes 19 (2.9) 6 (2.6) 25 (2.8) incomplete lbbb no 656 (99.1) 226 (97.8) 882 (98.8) 0.306 yes 6 (0.9) 5 (2.2) 11 (1.2) left anterior hemi-block no 570 (86.1) 205 (88.7) 775 (86.8) 0.307 yes 92 (13.9) 26 (11.3) 118 (13.2) left posterior hemi-block no 662 (100.0) 229 (99.1) 891 (99.8) 0.067 yes 0 (0.0) 2 (0.9) 2 (0.2) ivcd no 648 (97.9) 218 (94.4)7 866 (97.0) 0.007 yes 14 (2.1) 13 (5.6) 27 (3.0) bifascicular block no 546 (82.5) 193 (83.5) 739 (82.8) 0.710 yes 116 (17.5) 38 (16.5) 154 (17.2) abnormal r wave progression no 639 (96.5) 211 (91.3) 850 (95.2) 0.002 yes 23 (3.5) 20 (8.7) 43 (4.8) q wave in inferior leads no 624 (94.3) 219 (94.8) 843 (94.4) 0.756 yes 38 (5.7) 12 (5.2) 50 (5.6) q wave in lateral leads no 659 (99.5) 231 (100.0) 890 (99.7) 0.573 yes 3 (0.5) 0 (0.0) 3 (0.3) q wave in precordial leads no 642 (97.0) 224 (97.0) 866 (97.0) 0.994 yes 20 (3.0) 7 (3.0) 27 (3.0) prolonged qt interval no 548 (82.9) 181 (78.7) 729 (81.8) 0.154 yes 113 (17.1) 49 (21.3) 162 (18.2) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 8 table 1: baseline characteristics and first electrocardiographic (ecg) findings of covid-19 patients variable alive (n=662) dead (n=231) total (n=893) p age (year; mean ± sd) 58.4±16.9 71.4±13.9 61.8±17.2 <0.001 st segment normal 527 (79.6) 159 (68.8) 686 (76.8) 0.002 elevation 21 (3.2) 15 (6.5) 36 (4.0) depression 114 (17.2) 57 (24.7) 171 (19.1) abnormal t wave no 511 (77.2) 161 (69.7) 672 (75.3) 0.023 yes 151 (22.8) 31.7 (30.3) 221 (24.7) abnormal t wave no 511 (77.2) 161 (69.7) 672 (75.3) 0.023 yes 151 (22.8) 31.7 (30.3) 221 (24.7) ivcd: interventricular conduction delay; lbbb: left bundle branch block; rbbb: right bundle branch block; sd: standard deviation. *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. #, ventricular arrhythmia includes premature ventricular contraction, and ventricular tachycardia. table 2: multivariate analysis of abnormal finding in first electrocardiography and in-hospital mortality of covid-19 patients variable relative risk 95% ci p male sex 1.110 0.913-1.350 0.292 increase in age 1.036 1.029-1.044 <0.001 sinus tachycardia 2.342 1.84-2.982 <0.001 supraventricular arrhythmia* 1.688 1.250-2.280 0.001 ventricular arrhythmia# 1.854 1.154-2.979 0.011 ivcd 1.608 1.129-2.291 0.009 abnormal r wave progression 1.766 1.260-2.474 0.001 abnormal t wave 1.108 0.909-1.350 0.308 ci: confidence interval; ivcd: interventricular conduction delay. *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. #, ventricular arrhythmia includes premature ventricular contraction and ventricular tachycardia. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e45 table 3: second electrocardiographic findings of covid-19 patients variable alive (n=218) dead (n=110) total (n=328) p sinus tachycardia no 165 (75.7) 63 (57.3) 228 (69.5) 0.001 yes 53 (24.3) 47 (42.7) 100 (30.5) sinus bradycardia no 188 (86.2) 105 (95.5) 293 (89.3) 0.011 yes 30 (13.8) 5 (4.5) 35 (10.7) supraventricular arrhythmia* no 203 (93.1) 86 (78.2) 289 (88.1) <0.001 yes 15 (6.9) 24 (21.8) 39 (11.9) ventricular arrhythmia# no 213 (97.7) 104 (94.5) 317 (96.6) 0.191 yes 5 (2.3) 6 (5.5) 11 (3.4) rbbb no 208 (95.4) 103 (93.6) 311 (94.8) 0.493 yes 10 (4.6) 7 (6.4) 17 (5.2) lbbb no 209 (95.9) 102 (92.7) 311 (94.8) 0.225 yes 9 (4.1) 8 (7.3) 17 (5.2) incomplete rbbb no 215 (98.6) 109 (99.1) 324 (98.8) 0.716 yes 3 (1.4) 1 (0.9) 4 (1.2) incomplete lbbb no 214 (98.2) 108 (98.2) 322 (98.2) >0.999 yes 4 (1.8) 2 (1.8) 6 (1.8) left anterior hemi-block no 194 (89.0) 97 (88.2) 291 (88.7) 0.827 yes 24 (11.0) 13 (11.8) 37 (11.3) left posterior hemi-block no 218 (100.0) 108 (98.2) 326 (99.4) 0.112 yes 0 (0.0) 2 (1.8) 2 (0.6) ivcd no 215 (98.6) 104 (94.5) 319 (97.3) 0.065 yes 3 (1.4) 6 (5.5) 9 (2.7) bifascicular block no 186 (84.9) 90 (81.8) 276 (83.9) 0.469 yes 33 (15.1) 20 (18.2) 53 (16.1) abnormal r wave progression no 208 (95.4) 99 (90.0) 307 (93.6) 0.059 yes 10 (4.6) 11 (10.0) 21 (6.4) q wave in precordial leads no 206 (94.5) 106 (96.4) 312 (95.1) 0.458 yes 12 (5.5) 4 (3.6) 16 (4.9) prolonged qt interval no 171 (79.2) 87 (81.3) 258 (79.9) 0.651 yes 45 (20.8) 20 (18.7) 65 (20.1) st segment normal 163 (74.8) 70 (63.6) 233 (71.0) 0.037 elevation 15 (6.9) 6 (5.5) 21 (6.4) depression 40 (18.3) 34 (30.9) 74 (22.6) abnormal t wave no 162 (74.3) 64 (58.2) 226 (68.9) 0.003 yes 56 (25.7) 46 (41.8) 102 (31.1) ivcd: interventricular conduction delay; lbbb: left bundle branch block; rbbb: right bundle branch block; sd: standard deviation. *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. #, ventricular arrhythmia includes premature ventricular contraction, and ventricular tachycardia. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 10 table 4: multivariate analysis of abnormal finding in second electrocardiography and in-hospital mortality of covid-19 patients variable relative risk 95% ci p increase in age 1.022 1.014-1.031 <0.001 sinus tachycardia 2.222 1.597-3.0915 <0.001 supraventricular arrhythmia* 1.632 1.792-3.866 <0.001 ventricular arrhythmia# 1.510* 0.754 -3.022 0.244 abnormal r wave progression 2.151 1.206-3.834 0.009 abnormal t wave 1.590 1.221-2.069 0.001 ci: confidence interval *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. #, ventricular arrhythmia includes premature ventricular contraction, and ventricular tachycardia. table 5: changes in clectrocardiographic findings during hospitalization in covid-19 patients variable alive (n=218) dead (n=110) total (n=328) p sinus tachycardia no 193 (88.5) 99 (90.0) 292 (89.0) 0.688 yes 25 (11.5) 11 (10.0) 36 (11.5) sinus bradycardia no 200 (91.7) 106 (96.4) 306 (93.3) 0.114 yes 18 (8.3) 4 (3.6) 22 (6.7) supraventricular arrhythmia* no 213 (97.7) 102 (92.7) 315 (96.0) 0.029 yes 5 (2.3) 8 (7.3) 13 (4.0) ventricular arrhythmia# no 213 (97.7) 106 (96.4) 319 (97.3) 0.483 yes 5 (2.3) 4 (3.6) 11 (3.4) lbbb no 215 (98.6) 106 (96.4) 321 (97.9) 0.174 yes 3 (1.4) 4 (3.6) 7 (2.1) left anterior hemi-block no 215 (98.6) 106 (96.4) 321 (97.9) 0.174 yes 3 (1.4) 4 (3.6) 7 (2.1) bifascicular block no 212 (97.2) 105 (95.5) 317 (96.6) 0.394 yes 6 (2.8) 5 (4.5) 11 (3.4) prolong qt interval no 197 (91.2) 97 (90.7) 294 (91.0) 0.871 yes 19 (8.8) 10 (9.3) 29 (9.0) abnormal r wave progression no 214 (98.2) 106 (96.4) 320 (97.6) 0.449 yes 4 (1.8) 4 (3.6) 8 (2.4) st segment no 214 (98.2) 100 (90.9) 314 (95.7) 0.006 yes 4 (1.8) 10 (91) 14 (4.3) abnormal t wave no 212 (97.2) 103 (93.6) 315 (96.0) 0.137 yes 6 (2.8) 7 (6.4) 13 (4.0) lbbb: left bundle branch block. *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. #, ventricular arrhythmia includes premature ventricular contraction, and ventricular tachycardia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e45 table 6: multivariate analysis of changes in electrocardiographic findings during hospitalization and in-hospital mortality of covid-19 patients variable relative risk 95% ci p supraventricular arrhythmia 1.973 1.234-3.154 0.005 st elevation/depression 2.296 1.574-3.349 <0.001 ci: confidence interval. *, supraventricular arrhythmia includes atrial fibrillation, atrial flutter, premature atrial contraction, atrial tachycardia, and multifocal atrial tachycardia. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e54 rev i ew art i c l e safety and adverse events related to inactivated covid19 vaccines and novavax; a systematic review omid dadras1,2, esmaeil mehraeen3, amirali karimi4, marcarious m. tantuoyir4,5, arian afzalian4, newsha nazarian6, hengameh mojdeganlou7, pegah mirzapour1, ahmadreza shamsabadi8, mohsen dashti9, afsaneh ghasemzadeh9, farzin vahedi4, parnian shobeiri4, zahra pashaei1, seyedahmad seyedalinaghi1∗ 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. school of public health, walailak university, nakhon si thammarat, thailand. 3. department of health information technology, khalkhal university of medical sciences, khalkhal, iran. 4. school of medicine, tehran university of medical sciences, tehran, iran. 5. biomedical engineering unit, university of ghana medical center (ugmc), accra, ghana. 6. school of medicine, islamic azad university, tehran, iran. 7. department of pathology, urmia university of medical sciences, urmia, iran. 8. department of health information technology, esfarayen faculty of medical sciences, esfarayen, iran. 9. department of radiology, tabriz university of medical sciences, tabriz, iran. received: april 2022; accepted: may 2022; published online: 7 july2022 abstract: introduction: knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. therefore, this study aimed to systematically review the adverse events reported for inactivated vaccines and novavax. methods: in this systematic review, the databases of pubmed, scopus, cochrane, and web of science were searched on september 15, 2021. then we identified the eligible studies using a two-step title/abstract and full-text screening process. data on the subjects, studies, and types of adverse events were extracted and entered in a word table, including serious, mild, local, and systemic adverse events as well as the timing of side effects’ appearance. results: adverse effects of inactivated coronavirus vaccines side effects were reported from phases 1, 2, and 3 of the vaccine trials. the most common local side effects included injection site pain and swelling, redness, and pruritus. meanwhile, fatigue, headache, muscle pain, fever, and gastrointestinal symptoms including abdominal pain and diarrhea were among the most common systemic adverse effects. conclusion: this systematic review indicates that inactivated covid-19 vaccines, including sinovac, sinopharm, and bharat biotech, as well as the protein subunit vaccines (novavax) can be considered as safe choices due to having milder side effects and fewer severe life-threatening adverse events. keywords: adverse effects; bbv152 covid-19 vaccine; covid-19; covid-19 vaccines; recombinant sars-cov-2 vaccine nvx-cov2373; safety; sars-cov-2; sinovac covid-19 vaccine; vaccines, inactivated cite this article as: dadras o, mehraeen e, karimi a, tantuoyir m.m, afzalian a, nazarian n, et al. safety and adverse events related to inactivated covid-19 vaccines and novavax; a systematic review. arch acad emerg med. 2022; 10(1): e54. https://doi.org/10.22037/aaem.v10i1.1585. ∗corresponding author: seyedahmad seyedalinaghi, iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. email:s_a_alinaghi@yahoo.com, tel: 0098 (021) 66581583, orcid: http://orcid.org/0000-0003-3210-7905. 1. introduction covid-19 was first found in wuhan, china, in december of 2019. it is caused by a new coronavirus, called sars-cov-2. the virus is similar to the other two coronaviruses, sars-cov and mers-cov (1, 2). covid-19 manifestations are coughing, fever or chills, and shortness of breath; thus, it may be challenging to distinguish it from influenza (3-5). covidthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 2 19 spreads more easily through droplets and aerosols than sars, mers, and influenza (5). given these characteristics, it quickly spread from its source to other areas and countries, causing a pandemic across the world. this has been a huge problem for health systems around the world. it is still important to curb the virus by wearing masks and avoiding public gatherings or closing schools, even though these measures have had a big impact on daily life and the world economy (6). because there is not yet a standard treatment for covid19, vaccines must be administered quickly to stop the global pandemic. influenza and poliovirus vaccines have been demonstrated to be safe and efficacious when made from inactivated viruses (7). having been used for a long time gives them several benefits, such as well-developed manufacturing methods and the ability to easily scale production and storage up and down. inactivated sars-cov-2 vaccines have been shown to generate significant levels of neutralizing antibody titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (8-10). sars-cov-2 vaccines have shown strong neutralizing antibody responses and effectiveness against covid-19 during clinical studies conducted in different countries (11-15). sars-cov-2 vaccines manufactured by sinovac life sciences/coronavac (china) and beijing institute of biological products/sinopharm (china) have received conditional marketing approval from the china national medical products administration and have been placed on who’s emergency use listing (16, 17) so far. nvx-cov2373 (novavax, usa) and zf2001 (longcom, china), two covid19 protein subunit vaccines, are now undergoing phase-3 clinical studies (18, 19). an early study found that the vaccines, nvx-cov2373 (novavax, usa) and zf2001 (longcom, china), both of which imitate the receptor-binding domain (rbd) of the sars-cov-2 s protein, successfully prevent infection and generate high antibody titers against the sarscov-2 s protein (18, 19). evidence to assist in selection of vaccines for populationbased immunization in diverse areas is limited. to give additional data to optimize the use of the covid-19 vaccines, we performed a systematic review of the adverse events of the existing inactivated vaccines and novavax to determine their safety. 2. methods this review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. a systematic search of relevant records was carried out in the online databases using selected keywords on september 15th, 2021. 2.1. study objective the aim of the present study was to evaluate the safety and side effects of the inactivated vaccines of covid-19 and novavax. 2.2. databases consistent with the cochrane handbook of systematic reviews, pubmed, scopus, web of science, and cochrane were selected databases in this study. 2.3. search terms we designed our search strategy using the keywords from previous articles and the medical subject headings (mesh) terms. the search was conducted on september 15, 2021. supplementary material 1 includes the search strategy for all the databases. the following query demonstrates the pubmed search strategy: ((((((covid-19[title]) or (sars-cov-2[title])) or (sarscov2[title])) or (2019-ncov[title])) or (novel coronavirus [title])) and ((((vaccine*[title]) or (vaccination[title])) or (vaccinated[title])) or (immunization[title]))) and (((((safety[title]) or (side effect*[title])) or (adverse event*[title])) or (adverse effect*[title])) or (adverse reaction*[title])) 2.4. inclusion/exclusion criteria we included the original studies that assessed the safety and adverse events related to inactivated covid-19 vaccines and novavax. the following were the exclusion criteria: 1) non-original studies, including review articles, metaanalyses, and editorials without original data 2) abstracts/conference abstracts or unavailability of full texts 3) protocols of clinical trials or ongoing clinical trials with unpublished results 4) studies on types of vaccines rather than inactivated vaccines and novavax or the studies that only reported the efficacy of inactivated vaccines and novavax without reporting their adverse events 5) case reports 2.5. screening and data screening records from the start until september 15, 2021, were downloaded into the endnote software. a two-phase screening was done. firstly, after removing duplicates, the title and abstract of articles were assessed against the inclusion and exclusion criteria. then, a full-text screening was completed by two reviewers. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e54 2.6. data extraction this study aimed to evaluate the safety and adverse events related to inactivated covid-19 vaccines and novavax. to achieve this goal, data for the following variables were extracted for further analysis: the name of the first author, year of publication, country / ethnic group, type of study, manufacturer, phase of the study, sample population, age, gender, serious side effects, time from injection to adverse effects, local side effects, as well as systemic adverse effects. 2.7. quality assessment we assessed the quality of the studies using the newcastleottawa scale (nos) checklist, which allocates a score of 0-9 to each study based on selection, comparability, and exposure/outcome(20). studies that scored 4 or below were considered of poor quality (table 2). 3. results we initially identified a total of 1062 relevant records; however, only 515 remained after duplicate removal. of the remaining records, 171 and 325 were removed in title/abstract and full-text screenings, respectively. therefore, 19 studies appeared to be eligible and entered the qualitative synthesis (figure 1). analysis of the included studies identified inactivated coronavirus vaccines including bharat biotech (covaxin), sinovac (coronavac), and sinopharm. sinopharm was the most commonly reported inactivated vaccine. perfusion s vaccine was also reported in one study. sinovac (coronavac) vaccine had most of its clinical trials in china and a few other countries like turkey, brazil, indonesia, and the philippines. bharat biotech (covaxin) on the other hand was only clinically trialed in india, while sinopharm went through trials mostly in china, the usa, and united arab emirates. perfusion s vaccine was also trialed in the us. these studies reported adverse effects from phases 1, 2, and 3 of the vaccine trials. most of these reported trials involved subjects that were 18 years and above with very few trials conducted in all age groups. the most common local side effects included pain, redness, pruritus, induration, urticaria, stiffness, and swelling at the site of the injection; while fatigue, body pain, headache, skin rashes, sleepiness, systemic reactogenicity, anorexia, cough, edema, joint pain, chills, muscle pain, fever, malaise, and gastrointestinal symptoms like diarrhea and constipation were the most common systemic side effects (table 1). the majority of the studies reported no serious side effects for the vaccines. nevertheless, very few studies reported serious adverse effects like hypertension, chest pain, thrombocytopenia, acute macular neuroretinopathy, limb weakness, limb shaking, menstruation, as well as episcleritis, anterior scleritis, paracentral acute middle maculopathy, and subretinal fluid. there was no documented death in our analysis (table 1). none of the studies were of poor quality. the mean score of the studies was 7.9 (table 2). the most commonly encountered problem based on the nos checklist was the lack of adequate matching of cases and controls, present in some of the observational studies. 4. discussion this study only focused on inactivated covid-19 vaccines that have been approved by the who including sinovac (coronavac), sinopharm (bbip-corv (vero cells)), and bharat biotech (covaxin) as well as a protein subunit vaccine (novavax). bharat has been trialed 7 times in only one country (india) and it is being used and approved in 12 countries, while sinovac has been trailed 27 times in 8 countries and approved in 48 countries. sinopharm, on the other hand, had 19 trials in 10 countries and is widely used in 80 countries (21). clinical trials have been conducted under unconventional swift circumstances, hence necessitating the extreme care for patient safety to gain the trust of the public and the medical community in procedures used to develop the vaccine, as the safety concerns regarding the covid-19 vaccines are major obstacles to scaling up the vaccine uptake (22, 23). reporting these events is of paramount importance in tackling vaccine hesitancy and ultimately curtailing the pandemic (24). a multinational study conducted on adverse effects of the covid-19 vaccines hypothesizes that there could be a huge variety in side effects due to diversity in age groups and gender as well as high heterogeneity in populations. consequently, single studies should be interpreted with extreme caution and account for the effect of potential confounders (25). serious adverse events (saes) after vaccine injection include life-threatening events, congenital anomaly or birth defect, death, inpatient hospitalization, significant disruption of the ability to carry out usual life activities, as well as an event that may require medical intervention. on the other hand, common or mild adverse events encompass local and systemic side effects that are considered non-life-threatening and often spontaneously resolve without any medications (26). 4.1. sinopharm from our study, this vaccine was found to be the most commonly used inactivated covid-19 vaccine. this phenomenon has been attributed to the higher number of countries that have approved the sinopharm vaccine to be used within their boundaries. furthermore, sinopharm has been widely reported to be safe with barely any serious side effects except for some mild to moderate complications such as the pain and firmness at the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 4 point of injection regardless of the number of doses taken (27-29). although some studies reported no adverse effects at all, the most common local side effects from this vaccine reported in various studies include redness (erythema), urticaria, swelling, induration, pain, and skin itching at the injection site (30-32). concerning systemic side effects, fatigue, fever, inappetence, headache, dizziness, muscle and body pain, nausea, vomiting, joint pain as well as gastrointestinal complications like constipation and diarrhea were mostly associated with this type of vaccine(31, 33). interestingly, a study found that this vaccine could be associated with a sore or dry throat, clogged nose, and runny nose as compared to other types of vaccines (34). despite most reports suggesting that the sinopharm vaccine presents mild side effects, the duration of these side effects and the time from injection to the appearance of the side effects varied depending on the dose. the time taken for side effects to appear typically ranges from 9 hours after to about 15 days after the first dose. the second dose and booster doses could take a longer duration up to 28 days for the side effects to appear. however, these adverse effects have been reported to be self-limiting and usually resolve within 1-3 days (27, 28, 30, 32-37). these features exhibited by the sinopharm vaccine may reflect on the safety profile of the sinopharm vaccine; however, longterm side effects should also not be ignored (29). contrary to the numerous reports of sinopharm being a quiet vaccine with no serious adverse events (27-30, 32, 38), very few studies have reported serious adverse effects. a study reported ocular complications 5.2 days post-vaccination that presented in the form of uveitis, central serous chorioretinopathy, chronic serous pigment epithelial detachment, blurry vision, sudden paracentral scotoma & hemorrhage, episcleritis, anterior scleritis, acute macular neuroretinopathy, paracentral acute middle maculopathy, and subretinal fluid. nevertheless, there was no causal relationship established in this study (37). thrombocytopenia, irregular heartbeats, abnormal blood pressure, chest distress, palpitation, shortness of breath, limb weakness, and limb shaking were also reported as saes in some studies (34, 35). this may be similar to the findings of fan y et al. in their study describing inactivated vaccines to be associated with serious metabolic, musculoskeletal, immune system, and renal disorders (39). however, most of these saes appeared to be unrelated to the vaccine and resolved with appropriate treatment with no mortality (27, 35). these adverse effects may be influenced by the age group and gender as suggested by li et al. (25) and saeed et al. with females experiencing more ses in their study (40), but aga et al. and guo et al. stipulated that these adverse effects are not dependent on gender, dose, or age (27, 28, 39). therefore, further multinational studies are recommended to explore the potential side effects of the vaccine in populations with different demographic backgrounds. 4.2. sinovac (coronavac) another commonly used inactivated covid vaccine is sinovac (coronavac) vaccine. various studies have reported this type of vaccine to induce mild to moderate side effects. all the studies analyzed in this study reported injection site pain to be the most common local side effect of the sinovacvaccine (41-45). it has been well documented that sinovac shots are associated with injection site pain, which occurs more often after the second dose as compared to the first dose. other local adverse events include swelling, discoloration, induration, itching, pruritus, erythema (redness), abdominal pain, and paranesthesia at the injection site (4147). these local side effects are self-limiting; hence, they resolve in a short period. though these ses do not last long, the systemic side effects may take a longer time to resolve. the most common systemic side effects are fever, sleepiness, fatigue, muscle pain, headache, diarrhea, vomiting, allergy, arthralgia, rash, mucocutaneous eruption, oral hypoesthesia, hypoesthesia, peripheral edema, abdominal distention, drowsiness, joint pain, hypersensitivity, runny and stuffy nose, lymphadenopathy, cough, and loss of appetite. among these symptoms, fatigue is the most frequent systemic adverse reaction to the sinovac vaccine (33, 41, 43, 44). additionally, there is no significant variation in symptom presentation among different age groups (42). notably, sinovac injection is associated with no lifethreatening adverse events. the evidence from phases 1 and 2 trials reported no vaccine-related mortality or grade 4 adverse events so far (41, 46). however, sporadic serious adverse events were reported in separate studies conducted by zhang et al. and wu et al. (43, 47). they reported pneumonia, numbness of limbs, chest pain, palpitation, hypertension, and menstruation as serious side effects that occurred in people after sinovac vaccination; however, these saes appeared to be vaccine-unrelated (42, 47). adverse events of the sinovac vaccine are expected to occur within 7 days after the first dose of the vaccine but it may take up to 28 days as reported by some studies (42, 45). additionally, the second dose may elicit side effects from 14 days post-vaccination. the safety profile of this vaccine from clinical trials in phases 1 and 2 postulates that it is safe and well-tolerated in various age groups. 4.3. bharat biotech the bharat biotech vaccine was found to be the least used inactivated corona vaccine. its clinical trials are comparable to the extent to which it is being used, but this may not imply its efficacy and safety profile. from the phase 1 and 2 trials, this vaccine has been reported to be well-tolerated by all the subjects with no significant differences in safety for various age groups (48). ella et al. reported that the most comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e54 mon adverse events that were deemed mild to moderate included pain at the injection site, redness at the injection site, itching, stiffness in the upper arm, and weakness in the injection arm as local side effects. furthermore, they reported the systemic side effects to entail body ache, fever, headache, malaise, weakness, and rashes (48). the time of ses appearance was not significantly different from other vaccines like sinopharm, sinovac, moderna, and astrazeneca (34). in the first shot, the covaxin produces ses within 0-7 days after injection, while the second dose was reported to elicit ses 7 days after receiving the vaccine. the covaxin produced no severe or life-threatening adverse effects in trials (48). however, these findings may as well require multi-site surveillance studies to ascertain the long-term effects and population heterogeneity effects since the current data may be insufficient to make a definitive conclusion. 4.4. novavax the novavax vaccine, which is a recombinant protein subunit vaccine, was reported by a single study in our analysis. despite concerns about the reactogenicity and side effects caused by the adjuvant in these vaccines, their desirable safety profiles due to the absence of live viral components, the addition of adjuvant to increase immunogenicity, and the ease of scalability of the recombinant protein serve as advantages for this type of vaccine. as a result, vaccine developers are drawn to this sort of vaccine. goepfert et al. reported no vaccine-related unintended adverse events or severe adverse events of special interest in phase 1 and 2 trials of the perfusion s (pres) protein vaccine. solicited side effects may appear after 7 days of taking the first dose. local side effects include pain, swelling, erythema, and grade 3 reaction; while systemic side effects include myalgia, malaise, fever, and headache. it was observed that systemic adverse events usually appeared on the second day after the second dose of the perfusion s (pres) protein vaccine. furthermore, immune responses in the elderly seem to be lower than younger age group independent of the number of doses (49). emerging clinical evidence from investigations of the nvx-cov2373 vaccine (novavax), a recombinant nanoparticle vaccine, revealed that it is safe and associated with a significant immune response in healthy adult participants. the majority of the time, reactogenicity is modest and brief. the frequency of significant adverse events seems to be minimal and comparable in all age groups (50). 4.5. limitations and recommendations the results of the present review may be limited in various aspects, as there is no specific system for the registration of covid-19 vaccine side effects in different countries. it is also limited in the aspect of data retrieval, since some studies were incomplete and their results had not been published yet. additionally, study subjects in the analyzed articles may have given biased reports of their adverse effects. this may be due to the difference in their level of education. consequently, the included studies may have had reporting bias; hence, there is an influence on the reliability of reported side effects. there are no scales for the severity of common side effects like pain and fatigue; hence, these reported side effects are patient-dependent, so mild ones may be neglected. also, we have no scale for comparison of these effects between studies and some reported adverse effects (e.g cardiovascular events) may be due to the co-existence of patients’ underlying diseases and vaccination. considering that the covid-19 vaccine rollout is relatively new, all of the adverse effects may not be well-known and the long-term effects are still undetermined. consequently, there is not sufficient evidence to affirm that these complications are solely due to the vaccines. therefore, multinational studies are recommended to address the influence of demographic heterogeneity on the manifestation of vaccines’ adverse effects as well as to determine the long-term adverse events of the inactivated covid vaccines. 5. conclusion this systematic review investigated the adverse effects of who-approved inactivated vaccines including sinovac (coronavac), sinopharm (bbip-corv ), and bharat biotech (covaxin) as well as a protein subunit vaccine (novavax). sinopharm followed by sinovac, and bharat were the most common inactivated vaccines trialed and used globally. the most common local side effects are pain, redness, and swelling at the injection site; while fatigue, body pain, headache, muscle pain, fever, and malaise were the most common systemic side effects. almost all these local and systemic adverse effects were self-limiting. therefore, they resolved within minutes to days post-vaccination. although few saes were reported after injecting inactivated and protein subunit vaccines, particularly with the sinopharm vaccine, no statistically significant relation was found between the vaccines and these side effects or any related mortality. hence, inactivated vaccines seem to be a safe choice due to their mild side effects and few life-threatening adverse events. 6. declarations 6.1. acknowledgments the present study was conducted in collaboration with khalkhal university of medical sciences, iranian research center for hiv/aids, tehran university of medical sciences, and walailak university. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 6 6.2. authors’ contributions (1) the conception and design of the study: esmaeil mehraeen, seyedahmad seyedalinaghi (2) acquisition of data: amirali karimi, marcarious m. tantuoyir (3) analysis and interpretation of data: arian afzalian, newsha nazarian, hengameh mojdeganlou (4) drafting the article: pegah mirzapour, ahmadreza shamsabadi, mohsen dashti, afsaneh ghasemzadeh, farzin vahedi, parnian shobeiri, zahra pashaei, omid dadras (5) revising it critically for important intellectual content: seyedahmad seyedalinaghi, esmaeil mehraeen, omid dadras (6) final approval of the version to be submitted: all authors 6.3. funding and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 6.4. competing interests the authors declare that there is no conflict of interest regarding the publication of this manuscript. 6.5. ethics approval and consent to participate not applicable 6.6. availability of data and material the authors stated that all 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(32) 2021 usa cohort sinopharm n/a 513 participants ≥70 male (67%), female (33%) no serious adverse reaction n/a pain fever headache 2 abuhammad, o. (29) 2021 usa cs sinopharm n/a 409 healthcare personnel n/a n/a no serious adverse reaction n/a pain, redness headache 3 al khames aga, q. a. (28) 2021 usa cs sinopharm n/a 340 participants 18–35, 36–55, >55 males (51.61%), female (48.39%) no serious adverse reaction 1.733±1.258, 1.405±0.916, 2.080±2.120 duration of signs and symptoms (days) pain, redness, urticaria, and swelling at the site of the injection fatigue, body pain, headache, muscle pain, fever, and gastrointestinal effects 4 ella, r. (48) 2021 india rct bharat i/ii 190 participants 12–65 male: (74%), female: (26%) no serious adverse reaction first dose: (days 0–7), second dose: at 7 days after the injection pain at the injection site, redness at the injection site, itching, stiffness in the upper arm, weakness in the injection arm body ache, fever, headache, malaise, weakness, rashes 5 goepfert, p.a. (49) 2021 usa rct perfusion s (pres) protein vaccine i/ii 439 participants 18-49 & ≥50 n/a no serious adverse reaction systemic & local adverse events appeared 7 days after vaccination (first dose) pain, swelling & erythema & grade 3 reaction myalgia, malaise fever & headache, 6 guo, w. (27) 2021 china rct vero cells (sinopharm) i/ii 784 participants ≥18 female: 58.9%(1849y), female: 40.55% (≥60 y) no serious adverse reaction during 7 days of the first dose pain fever headache fatigue nausea 7 han, b. (51) 2021 china rct coronavac (sinovac) i/ii 72 participants for phase i & 480 participant for phase ii 3-17 female: (57.7%) (phase i), female: (44.2%) (phase ii) no vaccinerelated serious adverse reaction during 7 days of the first dose pain swelling pruritus erythema fever headache cough anorexia diarrhea vomiting fatigue 8 hatmal, mm. (34) 2021 usa cs sinopharm (38.2% of participants received sinopharm 3.46% received moderna, n/a 2213 participants n/a n/a among sinopharm receivers: 2.5% showed severe adverse effects (e.g.,thrombocytopenia, mostly appeared within 9-12 h after injection pain swelling fatigue headache sleepiness chills myalgia joints pain fever dizziness nausea sweatin this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e54 table 1: characteristics of various inactivated and protein subunit covid-19 vaccines and their adverse effects id first author year country type vaccine name phase sample age gender serious adverse event time side effects local systemic sputnik, covaxin& johnson & johnson other 58.34% received astrazeneca &pfizer) irregular heartbeats, abnormal blood pressure,) 9 kaya, f. (46) 2021 turkey cs coronavac (sinovac) iii 329 participants mean age: 35.77 ±9.07 male: (51.5%), female: (48.5%) 33.2% no life-threatening adverse reaction was determined during 1.14 ±4 days after injection of the second dose pain redness swelling nausea vomiting fever headache fatigue allergy myalgia 10 pichi, f. (37) 2021 uae cs sinopharm iii 7 participants mean age: 41.4 male: (42.86%), female: (57.14%) 9 eyes of 7 patients presented with ocular adverse events: (e.g. uveitis, central serous chorioretinopathy, chronic serous pigment epithelial detachment, blurry vision, sudden paracentralscotoma& hemorrhage), episcleritis anterior scleritis acute macular neuroretinopathy paracentral acute middle maculopathy subretinal fluid within 15 days after injection of first dose n/a n/a 11 pu, j. (36) 2021 china rct sinopharm i 294 participants 18-59 male: (45%), female: (55%) no severe adverse event day 7 and 28 after booster pain, redness, swelling, and itch fatigue, rash, diarrhea, and fever 12 saeed, b. q. (40) 2021 u cs sinopharm n/a 1102 participants 18-80 male: (29%), female: (71%) n/a n/a pain, redness, tenderness, induration, and pruritus at the vaccination site fatigue, fever, nausea, diarrhea, cough, allergy, muscle pain, lethargy, abdominal pain, back pain, and headache this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 12 table 1: characteristics of various inactivated and protein subunit covid-19 vaccines and their adverse effects id first author year country type vaccine name phase sample age gender serious adverse event time side effects local systemic 13 tanriover, m. d. (41) 2021 turkey rct coronavac i/ii 11303 participants 18–59 male: (57.4%), female: (42.6%) n/a day 14 pain, pruritus, swelling, induration, paranesthesia, and erythema allergic reaction, rash, fatigue, headache, myalgia, vomiting, nausea, chill, fever, arthralgia, cough, and diarrhea 14 wang, g. (35) 2021 china rct sinopharm (aikewei) iii 11303 participants n/a n/a chest distress, palpitation, shortness of breath, limb weakness, limb shaking, general anesthesia, and transient vague 0–28 days local pain, skin itching, hand anesthesia, local induration, muscle soreness, and local rash dizziness, headache, fatigue, cough, nausea, dry mouth, low-grade fever, and chill 15 wu, z. (47) 2021 hebei, china rct coronavac i/ii phase i: 72 participants and phase ii: 349 participants ≥60 phase i: (male: 51.3%, female:48.7%) phase ii: (male: 48.42%, female: 51.58%) palpitation hypertension days 0 and 28 pain pruritus erythema swelling abdominal pain dizziness fever mucocutaneous eruption oral hypoesthesia fatigue diarrhea muscle pain rash hypoesthesia peripheral edema cough headache nausea anorexia abdominal distention vomiting drowsiness joint pains hypersensitivity 16 xia, s. (30) 2020 china rct sinopharm i/ii total: 481 participants, phase i: 96 participants were included and phase ii: 224 participants 18-59 phase i: (male: 39.5%, female: 60.5%) phase ii: (male: 36.6%, female: 63.4%) n/a days 0 and 28 itching, redness, swelling, and pain coughing headache, fatigue diarrhea fever, nausea, pruritus, and vomiting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e54 table 1: characteristics of various inactivated and protein subunit covid-19 vaccines and their adverse effects id first author year country type vaccine name phase sample age gender serious adverse event time side effects local systemic 17 xia, s. (38) 2021 china rct sinopharm (bbibpcorv ) i/ii phase i: 192 participants and phase ii: 448 participants 18–80 phase i (male: 47%, female: 53% ) phase ii: (male: 45%, female: 55%) n/a days 0 and 28 pain swelling itch redness induration fatigue, fever inappetence headache muscle pain nausea diarrhea, joint pain 18 zhang, m. x. (43) 2021 china cs coronavac n/a 1526 participants 18–60 male: (20.7%), female: (79.3%) numbness of limbs, chest pain, and menstruation days 0 and 28 pain, redness, swelling, induration, and itch muscle pain, fatigue stuffy, rash, headache, dizziness, vomiting, diarrhea, appetite impaired, runny nose, nausea, fever, cough, throat pain, allergic reaction, urticarial, lymphadenopathy 19 zhang, y. (45) 2021 china rct coronavac i/ii phase i: 144 participants phase ii: 600 participants 18–59 days 0 and 14 vaccination male: (44%), female: (56%) days 0 and 28 vaccinations male: (49%), female: (51%) n/a days 0 and 28 pain pain swelling redness, discoloration pruritus, fatigue diarrhea, fever, headache, nausea, cough hypersensitivity, muscle pain, and decreased appetite *time from injection to the appearance of adverse events. rct: randomized clinical trial; cs: cross sectional. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 14 table 2: the results of quality assessment of included studies using newcastle-ottawa scale (nos) tool the first author (reference) selection (out of 4) comparability (out of 2) exposure/outcome (out of 3) total score (out of 9) abu-halaweh, s.(32) **** ** 6 abu-hammad, o. (29) **** ** 6 al khames aga, q. a. (28) **** ** *** 9 ella, r. (48) **** ** *** 9 goepfert,p.a. (49) **** ** *** 9 guo, w. (27) **** ** *** 9 han, b. (51) **** ** *** 9 hatmal, mm. (34) **** ** 6 kaya, f. (46) **** *** 7 pichi, f. (37) **** *** 7 pu, j. (36) **** ** *** 9 saeed, b. q. (40) **** ** 6 tanriover, m. d. (41) **** ** *** 9 wang, g. (35) **** *** 7 wu, z. (47) **** ** *** 9 xia, s. (30) **** ** *** 9 xia, s. (38) **** ** *** 9 zhang, m. x. (43) **** ** 6 zhang, y. (45) **** ** *** 9 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014);2(4): 150 150 letter to editor door to electrocardiography (ecg) and needle times in patients with myocardial infarction mohammad kalantari meibodi* emergency medicine trauma research center, shiraz medical university, shiraz iran *corresponding author: mohammad kalantari meibodi; department of emergency medicine, nemazi hospital, zand avenue, zand square, shiraz 71937-11351, iran. tel/fax: +98 9151132998; email: kalantari_meibodi@yahoo.com dear editor: cute myocardial infarction is one of the most prevalent causes of hospitalization in emergency department. in united states 650,000 patients annually suffer from acute myocardial infarction and in iran ischemic heart diseases are considered as the second cause of mortality in population of 15-49 years (1). taking thrombolytic drugs leads to 40-50% decrease in mortality rate of such patients. based on the current standards, less than 10 and 30 minutes are estimated for appropriate door to electrocardiography (ecg) and door to needle times, respectively (2). in a study performed on 100 patients referred to the emergency department of nemazi hospital, shiraz, iran, through march 2013 to april 2014, the mean time from the chest pain starting to emergency ward admission was estimated more than 90 minutes. the mean time from admission to do ecg were 11 minutes at morning shift, 16 minutes at evening, and 23 minutes at night. also, the mean time from admission to ecg performing and thrombolytic therapy (door to needle) were around two times more than standard times and no significant difference was seen among the morning, evening, and night shifts. the mean door to needle time in one hospital of hamedan, iran, was reported around 84 minutes, in jahrom, iran, 190 minutes, and in three hospitals in tehran, iran, 44 minutes (3-5). the findings of previous studies showed a significant relation between crowdedness of the work shift and longer treatment time in patients with myocardial infarction. considering to the importance of door to needle time in improving the final outcome and decreasing the mortality rate of patients with ischemic heart disease, planning and correct training of hospital and pre-hospital staffs are critical for approaching these mean times to international standards. references: 1. forouzanfar mh, sepanlou sg, shahraz s, et al. evaluating causes of death and morbidity in iran, global burden of diseases, injuries, and risk factors study 2010. arch iran med. 2014;17(5):304-20. 2. zalenski rj, selker hp, cannon cp, et al. national heart attack alert program position paper: chest pain centers and programs for the evaluation of acute cardiac ischemia. ann emerg med. 2000;35(5):462-71. 3. zeraati f, homayounfar s, esna-ashari f, khalili m. fibrinolytic therapy in ccu instead of emergency ward: how it affects door to needle time? int j prev med. 2014;5(3):308. 4. hojjat m. time period between entrance of severe heart stroke patient to hospital and streptokinase injection by nurses. j crit care nurs. 2009;2(1):35-9. 5. tabriz aa, sohrabi m-r, kiapour n, yazdani s. factors associated with delay in thrombolytic therapy in patients with st-elevation myocardial infarction. j tehran heart cent. 2012;7(2):65-71. a mailto:kalantari_meibodi@yahoo.com emergency. 2022; 10(1): e22 le t t e r to ed i to r video laryngoscopy in emergency airway management a paradigm shift from ‘i’ to ‘we’; a letter to editor sadaf sheikh1∗, faisal shamim2 1. emergency physician, al-hayat international hospital, muscat, oman. 2. intensivist, aga khan university hospital, karachi, pakistan. received: january 2022; accepted: february 2022; published online: 20 march 2022 cite this article as: sheikh s, shamim f. video laryngoscopy in emergency airway management a paradigm shift from ‘i’ to ‘we’; a letter to editor. arch acad emerg med. 2022; 10(1): e22. https://doi.org/10.22037/aaem.v10i1.1474. dear editor; video and optical laryngoscopic devices are valuable changes in the airway management paradigm with the hope of dominating the field of emergent airway management. they contain essential technical details, which are valuable for peri-operative airway assessment. airway management experts are suggesting the technical benefits of vl. firstly, it has got a short learning curve for emergency physicians. it is a great tool for operators with no or little experience. it gives a better laryngeal view due to the camera on the blade’s distal end with macintosh-shaped blades and extra curved blades augment a view that is beyond the reach of macintosh-styled blades. the force applied while intubating with vl is far less than dl, which helps reduce the trauma to the oral cavity. vl has a higher success rate for intubation when used as the first line or rescue device and keeps the intubation attempts to a minimum (1-3). secondly, when the trainer can see the larynx on the screen when a trainee is performing largynoscopy, it helps them give instructions to the trainee to optimize the blade position and the placement of the endotracheal tube (ett) by marking important landmarks on the screen. thus, the trainee can complete this procedure without the trainer taking over, which is instrumental in rapid sequence intubations. vl enhances team work and clinical governance as the whole team can see the ett pass. these merits are even worth considering when intubating critically ill patients in the intensive care units. despite the merits of vl, few challenges are faced during its use and gaining experience. operators with standard macintosh laryngoscope cannot equate their skill in han∗corresponding author: sadaf sheikh; al-hayat international hospital, muscat, oman. e-mail: sheikh.sadaf@gmail.com, orcid: http://orcid.org/00000001-7457-0012. dling vl. the same applies to experience with one type of vl and trying to use another type. the reason is that there are numerous vl designs that require various techniques. for instance, c-mac has been used as a standard macintosh laryngoscope; whereas, the glidescope is used without tongue displacement (4, 5). insertion depth and direction of applied forces require attention as these devices are inserted less far and require the blade to be lifted vertically. this information would help the operator perform better and is vital for patient safety. a reasonable view of vocal cords with vl doesn’t necessarily warrant easy intubation as inexpert handling of vl leads to intubation failure and airway trauma. some cost-effective options entail ett with stylets to be flexed while perfoming intubation (5). we suggest using vl with extra-curved blade to enhance chances of seeing round the corner and with a separate screen to make it easier for the trainer to guide a trainee and other members of the team. vl is not a great tool when there is a significant limitation of mouth opening not allowing the insertion of the vl blade (5). a difficult scenario could be laryngoscopic paradox, which is defined as a difficult endotracheal passage despite a great view, so one must be aware of such concepts. vl may have had a poorer alignment of oral, pharyngeal and laryngeal axes as there are hyperangulated blades as well as standard geometry blades (5). so we feel the tool is only as good as the operator, so there is a need to train an operator in both dl and vl. we studied a combination of elements to address the technical concern of intubation. knowing the risks and benefits of emergency airway management and devices used is required for safe practice. dl should always be kept as a foremost skill and we advocate the use of vl as a preference skill in patients with cervical spine injuries or restricted mouth opening. it is yet to be determined if vl can cause a paradigm shift from dl in emergent airway management. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. sheikh and f. shamim 2 1. declarations 1.1. acknowledgments none. 1.2. authors’ contributions ss conceived the manuscript idea and drafting and fs supervised the manuscript formation. 1.3. funding and supports none to declare. 1.4. conflict of interest none to declare. references 1. bair ae, filbin mr, kulkarni rg, walls rm. the failed intubation attempt in the emergency department: analysis of prevalence, rescue techniques, and personnel. erratum in: j emerg med. 2002;23(3):325. 2. walls rm, brown iii ca, bair ae, pallin dj, investigators ni. emergency airway management: a multi-center report of 8937 emergency department intubations. j emerg med. 2011;41(4):347-54. 3. niforopoulou p, pantazopoulos i, demestiha t, koudouna e, xanthos t. video-laryngoscopes in the adult airway management: a topical review of the literature. acta anaesthesiol scand. 2010;54(9):1050-61. 4. thong s, lim y. video and optic laryngoscopy assisted tracheal intubation–the new era. anaesth intensive care. 2009;37(2):219-33. 5. wetsch wa, carlitscheck m, spelten o, teschendorf p, hellmich m, genzwürker hv, et al. success rates and endotracheal tube insertion times of experienced emergency physicians using five video laryngoscopes: a randomised trial in a simulated trapped car accident victim. eur j anaesthesiol. 2011;28(12):849-58. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2022; 10(1): e21 ca s e re p o rt right upper quadrant pain following endoscopic retrograde cholangiopancreatography; a case report lan thi nguyen1∗, dang hai do2, an duc thai2, hoa thi nguyen3 1. department of hepatobiliary surgery, vietduc university hospital, hanoi, viet nam. 2. department of general surgery, hanoi medical university, hanoi, viet nam. 3. center of anesthesia and surgical intensive care, vietduc university hospital, hanoi, viet nam. received: january 2022; accepted: february 2022; published online: 16 march 2022 abstract: endoscopic retrograde cholangiopancreatography (ercp) is a standard for diagnosing and treating hepatopancreatico-biliary (hpb) diseases in clinical settings. ercp-related complications are relatively common, ranging from 4 to 30%. the most common one is acute pancreatitis. ercp-related necrotizing pancreatitis accounts for 7.7% of ercp-related pancreatitis cases. this complication may still be misdiagnosed, which might lead to inappropriate treatment with a worse prognosis. here, we report a 34-year-old case with ercp-related necrotizing pancreatitis who was successfully managed, but initially misdiagnosed with biliary peritonitis. keywords: pancreatitis, acute necrotizing; peritonitis; cholangiopancreatography, endoscopic retrograde; case reports cite this article as: nguyen lt, do dh, thai ad, nguyen ht. right upper quadrant pain following endoscopic retrograde cholangiopancreatography; a case report. arch acad emerg med. 2022; 10(1): e21. https://doi.org/10.22037/aaem.v10i1.1535. 1. introduction endoscopic retrograde cholangiopancreatography (ercp) is a common tool for diagnosing and treating hepatopancreatico-biliary diseases. via direct vision of the bile duct, sphincterotomy and gallstone removal are conducted, and it has truly become the standard treatment for common bile duct (cbd) stone removal nowadays. ercp-related complications are relatively common, ranging from 4 to 30% [1]. most of these complications are not too serious and can be conservatively treated; however, the challenges lie in critical cases. the mortality rate was reported to be 0.5-1.5% and as high as 18% in duodenal injury (2, 3). pancreatitis, bleeding, perforation, and cholangitis are the most common complications. though the methods for diagnosis and treatment have been established, in some sophisticated cases, a misdiagnosis could still occur, which might lead to inappropriate treatment with a worse prognosis. we report successful surgical management for a 34-year-old case with ercp-related necrotizing pancreatitis, which was first misdiagnosed as biliary peritonitis. ∗corresponding author: lan thi nguyen; department of hepatobiliary surgery vietduc university hospital, 40 trang thi street, hoan kiem, hanoi, 100000, viet nam. tel: +84983289213, email: dr.nguyenlanvd@gmail.com, orcid: https://orcid.org/0000-0002-9735-0175. 2. case presentation a 34-year-old woman came to the emergency department with the symptoms of right upper quadrant pain and a mild fever for the past two weeks. her husband reported a history of choledocholithiasis six months ago without any intervention. three days before hospitalization, the patient underwent sphincterotomy and stone removal via ercp in a regional hospital. the next day, she had intense pain and a high temperature (39°c). a computed tomography (ct) scan was conducted, which showed a sign of intra-abdominal free fluid, air, and fat stranding around the descending part of the duodenum; pancreatic parenchyma was normal, and there was no sign of infection. suspected of having an ercprelated perforation, ercp was conducted again, and a plastic stent was inserted in the biliary duct. simultaneously, abdominal drainage was also placed. however, her condition did not improve, and she was transferred to our hospital. the patient was admitted to our hospital in an unstable state, with tachycardia and 38.5°c fever. the examination showed abdominal distension and right-sided abdominal rebound tenderness and ascitic fluid was spotted. her blood test showed a high white blood cell count 13.2 g/l (98.7% neutrophil), calcium 1.43 mmol/l, elevated alanine aminotransferase and aspartate aminotransferase levels (69 and 225.1 u/l, respectively), and total bilirubin 13 umol/l, amylase 349.9 u/l, and lipase 338.5 u/l. bedside index for severthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem lt. nguyen and et al. 2 figure 1: coronal (left) and axial (right) views of abdominal magnetic resonance imaging (mri) at the time of admission. figure 2: the operative findings of the reported case. the non-perforated common bile duct (left) and peripancreatic fat necrosis caused by necrotizing pancreatitis (right). ity in acute pancreatitis (bisap) score was 3 points, ct severity index (ctsi) score was 0 points. the magnetic resonance imaging (mri) scan also suggested common bile duct perforation, with no clear sign of edematous or necrotizing pancreatitis (figure 1). an emergency operation was conducted 8 hours after admission. unexpectedly, the cause was not an ercp-related perforation (figure 2). intraoperative findings revealed peripancreatic fat necrosis throughout the abdomen, severe inflammation in the head of the pancreas, and small residual common bile duct (cbd) stones (figure 2). she underwent cbd clearance and stone removal with t-tube drainage, cholecystectomy, and witzel jejunostomy for feeding. four drainage tubes were placed in the transhepatic, peripancreatic, and doughlas regions. the calculated imrie score and acute physiology and chronic health evaluation (apache) ii scores were 2 and 9 points, respectively, which means the patient was under severe conditions with the risk of mortality of 11-18%. she was immediately admitted to the intensive care unit and was managed critically with analgesia, antibiotics, somatostatin, and proton pump inhibitors for 10 days. parenteral nutrition was applied and gradually turned into enteral nutrition via witzel jejunostomy. fortunately, the symptoms were relieved, and she was discharged 1 month later and was stable during the follow-up. 3. discussion the number of ercp procedures has been increasing in recent years, and ercp is becoming a practical tool for clinicians in diagnosing and treating hpb diseases (4, 5). though the risk of complications is as low as 4%, severe complications are truly a matter of concern. 10-20% of them are classified as “severe” with an overall mortality rate of 1-1.5% (6, 7). the most common complications include severe pancreatitis, perforation, and hemorrhagic shock. the overall risk increases in patients with sphincter of oddi dysfunction and sphincterotomy, while severe complications are associated with systemic disease, obesity, prolonged procedures(6). ercp-related necrotizing pancreatitis is a rare condition, accounting for 7.7% of ercp-related pancreatitis (8). in a study by fung on 72 patients with necrotizing pancreatitis, 6 of the cases (8.3%) were caused by ercp, and they also had a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e21 higher apache score (9). potential mechanisms may originate from mechanical, chemical, thermal, hydrostatic, biochemical factors. more specifically, papillary edema and spasms cause pancreatic fluid obstruction and pancreatitis. besides, activated pancreatic enzymes may damage and “autodigest” the parenchyma, while other factors such as injection pressure, iatrogenic, contrast media, and thermal injury may facilitate the process (10). a retrospective study by vege showed that 7.7% of severe acute pancreatitis cases were caused by ercp, with a mortality rate of 25%, slightly higher than other causes [8]. we also thought that a prognostic model should be adopted. however, since the patient had high apache ii and systemic inflammatory response syndrome (sirs)24-48 scores but low sirs0-24 score diagnosing her problem was really challenging (8, 11). at first, we misdiagnosed the patient with ercp-related bile duct perforation. examination showed right-sided rebound abdominal tenderness while the previous ercp showed thickened, inflamed papilla. mri also suggested a 3 mm perforated site in the lower part of the common bile duct, free fluid with no air in the peripancreatic and retroperitoneal region. emergency operation was chosen as previous evidence showed their benefits for patients with unstable conditions (12, 13). the symptoms were then determined to be caused by pancreatic necrosis and no sign of perforation was spotted. interestingly, a research by fathi on 2447 patients, with 6.9% complications, also showed that rebound tenderness did not occur in pancreatitis, but is suggestive of perforation (7). while the two conditions had different approaches, we thought that severe pancreatitis should not be excluded when peritonitis is present and prophylaxis for high-risk patients should be further studied. in this case, ercp and mri could not be a gold standard since the papilla was inflamed. if a patient’s conditions do not improve, the doctor should promptly head to another morbidity. and finally, witzel jejunostomy should be applied since it modulates the inflammatory response and reduces the rate of organ failure better than parenteral nutrition. 4. conclusion ercp-related necrotizing pancreatitis is a truly hazardous condition and might be misdiagnosed with other causes of peritonitis. a comprehensive study should be conducted, and larger studies are needed to find the best approach for its management. 5. declarations 5.1. acknowledgments we would like to express our thanks to all the medical staff in department of hepatobiliary surgery, center of anesthesia and surgical intensive care, medical imaging and nuclear medicine center ,for their contribution to diagnosis and management of the patient. 5.2. author contribution lan nt: main surgeon, wrote manuscript, did the management strategy dang dh: assistant surgeon, wrote manuscript, did the management strategy an nt: assistant surgeon, wrote manuscript hoa nt: did the anesthesia, data collection 5.3. source of support and funding none. 5.4. conflict of interest none. 5.5. data availability authors guarantee that data of the study is available and will be provided to anyone needing it. 5.6. ethical issues written informed consent was obtained from the patient for publication of this case report and accompanying images. no identity will be published, and all the published information will be used for education purposes only. the patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. the study was approved by our institutional research committee. references 1. freeman, m.l., adverse outcomes of ercp. gastrointest endosc, 2002. 56(6 suppl): p. s273-82. 2. stapfer, m., et al., management of duodenal perforation after endoscopic retrograde cholangiopancreatography and sphincterotomy. ann surg, 2000. 232(2): p. 191-8. 3. cotton, p.b., et al., endoscopic sphincterotomy complications and their management: an attempt at consensus. gastrointest endosc, 1991. 37(3): p. 383-93. 4. kroner, p.t., et al., use of ercp in the united states over the past decade. endosc int open, 2020. 8(6): p. 761-769. 5. park, j.m., et al., recent 5-year trend of endoscopic retrograde cholangiography in korea using national health insurance review and assessment service open data. gut liver, 2020. 14(6): p. 833-841. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem lt. nguyen and et al. 4 6. cotton, p.b., et al., risk factors for complications after ercp: a multivariate analysis of 11,497 procedures over 12 years. gastrointest endosc, 2009. 70(1): p. 80-8. 7. fathi, a., f. lahmi, and r. kozegaran, surgical management of ercp-related complications. gastroenterol hepatol bed bench, 2011. 4(3): p. 133-7. 8. vege, s.s., et al., endoscopic retrograde cholangiopancreatography-induced severe acute pancreatitis. pancreatology, 2006. 6(6): p. 527-30. 9. fung, a.s., g.g. tsiotos, and m.g. sarr, ercp-induced acute necrotizing pancreatitis: is it a more severe disease? pancreas, 1997. 15(3): p. 217-21. 10. sherman, s. and g.a. lehman, ercpand endoscopic sphincterotomy-induced pancreatitis. pancreas, 1991. 6(3): p. 350-67. 11. sinha, a., et al., systemic inflammatory response syndrome between 24 and 48 h after ercp predicts prolonged length of stay in patients with post-ercp pancreatitis: a retrospective study. pancreatology, 2015. 15(2): p. 105-10. 12. alfieri, s., et al., management of duodeno-pancreatobiliary perforations after ercp: outcomes from an italian tertiary referral center. surgical endoscopy, 2013. 27(6): p. 2005-2012. 13. theopistos, v., et al., non-operative management of type 2 ercp-related retroperitoneal duodenal perforations: a 9-year experience from a single center. gastroenterology res, 2018. 11(3): p. 207-212. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e11 https://doi.org/10.22037/aaem.v9i1.1053 le t t e r to ed i to r cardiologists’ knowledge and perception towards american heart association guidelines of cardiopulmonary resuscitation; a letter to editor sajjad ali1∗, annam zahid1, syed zahid jamal2, samahir tariq khan1, nisha lohana1, raahim ahmed1, nobia mehdi2 1. internal medicine department, ziauddin medical university, karachi, pakistan. 2. national institute of cardiovascular diseases, karachi, pakistan. received: december 2020; accepted: december 2020; published online: 2 january 2021 cite this article as: ali s, zahid a, jamal sz, tariq khan s, lohana n, ahmed r, mehdi n. cardiologists’ knowledge and perception towards american heart association guidelines of cardiopulmonary resuscitation; a letter to editor. arch acad emerg med. 2021; 9(1): e11. dear editor, sudden cardiac arrests (sca) pose massive threats to millions of lives worldwide. latest statistics report an annual death count of approximately 17.9 million for cardiovascular diseases (1). sca has caused 15% of these deaths (2) and is considered a major threat in both out-of-hospital and in-hospital settings. early identification and prompt cardiopulmonary resuscitation (cpr) is essential to increase the survival rate of sca patients from about 50% to 70% (3). to accomplish this increment, it is cardinal for each physician to be versed with the protocols of basic life support (bls) and advanced cardiac life support (acls). inadequacy with reference to both knowledge and awareness of guidelines has been witnessed in various low-income, lower-middle income, and middle-income countries such as greece, india, and nigeria (4-6). a study showed a significant lack of knowledge and practical approach regarding emergency cardiovascular care (ecc), among junior healthcare professionals (7). once training has been undertaken, it is indicated that skills may decline in a year, especially if not frequently performed or reviewed (8). several studies from pakistan have identified similar knowledge deficits regarding resuscitation guidelines among healthcare professionals (9, 10); however, no such research has been solely aimed at cardiologists. we, surveyed cardiologists’ theoretical knowledge of resuscitation guidelines, with an additional set of questions directed to test presumptive correlational factors, in national institute of cardiovascular diseases (nicvd), pak∗corresponding author: sajjad ali; department of internal medicine, ziauddin medical university, karachi, pakistan. mobile: + 923362179123, email: sajjad110@live.com, orcid: https://orcid.org/0000-0002-8024-5942. istan. results showed that out of the 215 studied cardiologists, only 162 (75.3%) cases were certified and had high mean test scores. surprisingly, the mean percentage of correctly marked theoretical questions was only 50.9 (ranging from 25.0 to 75.0). 212 participants believed that acls courses should be taken by students during medical school and 203 thought that annual retraining or refresher training of all healthcare professionals was necessary for having up-to-date knowledge on the aha guidelines. the length of time practicing in the sub-specialty had a negative correlation with knowledge scores (p = 0.039), as participants with less experience had the highest average score (52.03%). most respondents felt confident in their current knowledge of the aha guideline displaying an average knowledge score of 50.92%. the results of this study concerning mean knowledge scores of participants regarding aha-cpr guidelines based on different baseline characteristics are illustrated in table 1. table 2 shows the perception of participants regarding aha-cpr guidelines’ education and training. despite proven effectiveness of training courses, physicians may not fully comprehend the significance of recurring courses. the recommendation for refresher training, as proposed by previous study findings, is biannual i.e. every 6 months (11). even though optimal timelines for recommended retraining is yet unknown, it is deduced that regular retraining is required to gain proper resuscitation skills. another contributing element of resuscitation skills was lack of early training and exposure, especially during graduate school. medical school curriculum is largely based on longterm patient care, possibly overlooking acquaintance with emergency care approaches, rendering them unimportant in the early years. acls courses could be included under conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. ali and et. al 2 tinued medical education (cme), in our opinion. cme being included under cme makes it necessary for practitioners to undergo retraining to maintain licensure among other entitlements. hospitals or medical councils, can subsidize the financial burden of these costly acls courses in conjunction with cme. with reference to the disparities in healthcare, primarily caused by low national budgets dispensed for healthrelated causes, cardiologists in low and low-middle income countries should be monetarily assisted to gain life-saving skills for both in-hospital and out-of-hospital emergencies. it could be concluded that, theoretical knowledge of cpr guidelines among pakistani cardiologists remains unsatisfactory. regular refresher and/or retraining courses of acls might improve the quality of cpr techniques implemented and hence, downsize the global health burden caused by scas. we further believe that bls and acls courses should be integrated into the curriculums at all medical schools in pakistan. 1. declarations 1.1. acknowledgement 1.2. ethics approval the study has been approved by the ethical review committee of national institute of cardiovascular diseases (nicvd). reference number #: erc-31/2020. 1.3. informed consent subjects gave informed consent before filling out the questionnaire. 1.4. authors’ contributions sajjad ali: conceptualization, supervision, project administration, writing original draft, data curation, formal analysis. annam zahid: writing original draft, writing review & editing, data curation, resources, investigation. syed zahid jamal: supervision, project administration. samahir tariq khan: writing original draft, writing review & editing, investigation. nisha lohana: writing original draft, data curation. raahim ahmed: writing original draft, methodology. nobia mehdi: validation, supervision 1.5. conflict of interest the authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. 1.6. funding and support the authors received no financial support for the research, authorship, and/or publication of this article. references 1. organization wh. cardiovascular diseases (cvds) 2017 [13 october 2020]. available from: https://www.who.int/en/news-room/factsheets/detail/cardiovascular-diseases-(cvds). 2. mawani m, azam i, kadir mm, samad z, razzak ja. estimation of the burden of out-of-hospital traumatic cardiac arrest in karachi, pakistan, using a crosssectional capture-recapture analysis. international journal of emergency medicine. 2020;13:1-7. 3. panchal ar, berg km, hirsch kg, kudenchuk pj, del rios m, cabañas jg, et al. 2019 american heart association focused update on advanced cardiovascular life support: use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest: an update to the american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2019;140(24):e881-e94. 4. pantazopoulos i, aggelina a, barouxis d, papapanagiotou p, troupis g, kotsiomitis e, et al. cardiologists’ knowledge of the 2005 american heart association resuscitation guidelines: the athens study. heart & lung. 2011;40(4):278-84. 5. chaudhari ms, panchal nn, kamat hv, ganjiwale j. knowledge of 2015 basic life support (bls) guidelines among doctors and nursing staff of a rural based tertiary care hospital, in western india: current status and requirement. indian j anaesth. 2017;4:193-7. 6. osinaike b, aderinto d, oyebamiji e, dairo m, diya k. evaluation of knowledge of doctors in a nigrian tertiary hospital of cpr. nigerian medical practitioner. 2007;52(1):16-8. 7. skinner dv, camm a, miles s. cardiopulmonary resuscitation skills of preregistration house officers. british medical journal (clinical research ed). 1985;290(6481):1549. 8. yang c-w, yen z-s, mcgowan je, chen hc, chiang wc, mancini me, et al. a systematic review of retention of adult advanced life support knowledge and skills in healthcare providers. resuscitation. 2012;83(9):1055-60. 9. ghauri sk, javaeed a, shah f. dismal situation of cardio pulmonary resuscitation knowledge and skills among junior doctors in twin cities of pakistan. pakistan journal of medical sciences. 2019;35(5):1295. 10. zamir q, nadeem a, rizvi ah. awareness of cardiopulmonary resuscitation in medical-students and doctors in rawalpindi-islamabad, pakistan. jpma the journal of the pakistan medical association. 2012;62(12):1361. 11. berden h, willems ff, hendrick j, pijls n, knape j. how frequently should basic cardiopulmonary resuscitation training be repeated to maintain adequate skills? bmj: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e11 table 1: comparison of mean knowledge scores of participants regarding aha-cpr guidelines based on different baseline characteristics characteristics number score* p specialty invasive 87 48.63 ± 11.53 0.033 non-invasive 128 52.39 ± 10.37 gender male 171 50.54 ± 10.80 0.345 female 44 52.13 ± 11.74 positions attending/consultant 49 48.47 ± 11.72 0.105 resident 166 51.58 ± 10.69 institution university hospital 92 50.06 ± 11.13 0.215 educational research hospital 123 51.47 ± 10.88 years in specialty 0 5 175 52.03 ± 10.76 6 10 30 45.41 ± 11.12 11 20 6 45.83 ± 9.41 0.039* 21 30 3 50.00 ± 12.50 > 30 1 50.87 ± 0.00 updated with aha guidelines? yes 208 50.96 ± 11.08 0.438 no 7 48.21 ± 7.83 attendance in an acls course yes 179 51.46 ± 10.96 0.053 no 36 47.91 ± 10.77 time from last acls course (years) < 1 82 48.85 ± 10.26 1 – 5 123 52.23 ± 11.54 0.095 6 – 10 10 50.62 ± 7.48 acls certification? yes 162 51.81 ± 11.05 0.014* no 53 47.99 ± 10.38 *: measures are presented as mean ± standard deviation. acls: advanced cardiac life supports; aha: american heart association; cpr: cardiopulmonary resuscitation. british medical journal. 1993;306(6892):1576. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. ali and et. al 4 table 2: perception of participants regarding aha-cpr guidelines’ education and training perception number (%) would you recommend medical students to take an acls course? yes 212 (98.6) no 1 (0.5) maybe 2 (0.9) do you think healthcare professionals should update their knowledge on aha guidelines as per the annual update release? yes 203 (94.4) no 4 (19) maybe 8 (3.7) do you think acls courses should be re-evaluated frequently? yes 177 (82.3) no 8 (3.7) maybe 30 (14.0) do you think you are confident in saving a life with your aha guidelines knowledge? yes 209 (97.2) no 2 (0.9) maybe 4 (1.9) is it important for healthcare professionals from all disciplines to attend acls courses? yes 209 (97.2) no 2 (0.9) maybe 4 (1.9) data are presented as number and percentage. acls: advanced cardiac life support; aha: american heart association; cpr: cardiopulmonary resuscitation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2021; 9(1): e19 https://doi.org/10.22037/aaem.v9i1.1083 ca s e re p o rt thyrotoxic periodic paralysis with thyroid storm as the first presentation of graves’ disease; a case report tejaswee banavathu1, swapnil tripathi1, pankaj sukhadiya1, kamlesh ahari1, durga shankar meena1∗ mahendra kumar garg1 1. department of internal medicine, all india institute of medical sciences, jodhpur, india. received: january 2021; accepted: january 2021; published online: 17 february 2021 abstract: thyrotoxic periodic paralysis is a rare endocrine emergency that manifests as acute onset muscle weakness and hypokalaemia secondary to thyrotoxicosis. it mainly occurs due to rapid and dramatic intracellular shift of potassium resulting in hypokalaemia and acute flaccid paralysis. this condition predominantly affects males of asian descent, and presentation can range from mild generalized weakness to complete quadriplegia, as seen in our case. we herein report a case of a 40-year-old female, who presented to us with acute onset flaccid quadriplegia and thyroid storm, which is the first ever manifestation of previously undiagnosed grave’s disease. liver abscess was found to be the underlying trigger for thyrotoxic paralysis and thyroid storm. keywords: hypokalemic periodic paralysis; thyrotoxicosis; graves disease; quadriplegia; thyroid crisis cite this article as: banavathu t, tripathi s, sukhadiya p, ahari k, shankar meena d, kumar garg m. thyrotoxic periodic paralysis with thyroid storm as the first presentation of graves’ disease; a case report. arch acad emerg med. 2021; 9(1): e19. 1. introduction periodic paralysis and thyroid storm are two different manifestations of thyrotoxicosis-related medical emergencies, which are life-threatening without prompt diagnosis and treatment (1, 2). thyrotoxic periodic paralysis (tpp) is the acquired form of hypokalaemic paralysis, which usually occurs after the second or third decade of life. the incidence of tpp among the western and asian population is around 0.1% and 1.8%, respectively (3). hypokalaemic paralysis with thyrotoxic crisis, as an initial presenting feature of hyperthyroidism, is rarely reported in the literature (4). our case had both of these features on the first hospital visit along with an occult liver abscess, which was the probable trigger for tpp. diagnosis of tpp is often overlooked, which may have fatal consequences in the form of cardiac arrhythmias and respiratory paralysis (5). emergency physicians should have a high index of suspicion of tpp while treating a case of hypokalaemic paralysis. ∗corresponding author: durga shankar meena; room no134, medicine opd block, department of internal medicine, all india institute of medical sciences, jodhpur, rajasthan, india, 342005. email: dsmims14@gmail.com, tel: +91 9772200453, orcid: 0000-0001-9524-5278 2. case presentation a 40-year-old asian female presented to the emergency department with complaints of high-grade fever associated with palpitation for 7 days, loose stools for 2 days and altered sensorium for the last 1 day. she had a history of episodic right upper quadrant pain and weight loss for the last 1 month. no history of blood in the stool, cough, chest pain, headache, or vomiting could be elicited. she had not had similar episodes in the past. on presentation, she was drowsy with a glasgow coma score (gcs) of e3v3m4, febrile (temperature: 100.8◦f), blood pressure of 98/68 mmhg, pulse rate of 160/minutes, and respiratory rate of 24/minutes. general physical examination revealed a thin-built female with pallor and acral hypopigmentation (present since birth). neurological examination showed flaccid paralysis of all limbs with power of 1/5 and diminished reflexes. no signs of meningeal irritation were present. no sensory or cranial nerve deficit was detected. systolic flow murmur was heard on cardiac auscultation suggestive of hyperdynamic circulation. rest of the systemic examination was unremarkable. based on the clinical findings, acute transverse myelitis, guillain-barre syndrome (gbs) and periodic paralysis were considered as differential diagnoses of acute flaccid paralysis. magnetic resonance imaging (mri) of spine and nerve conduction studies were normal, which ruled out acute transverse myelitis and gbs. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. banavathu et al. 2 arterial blood gas analysis revealed serum potassium of 2.23 mmol/l with normal acid-base status. other blood investigations are tabulated in table 1. electrocardiogram showed sinus tachycardia with st segment depression in v3-v6. the initial diagnosis of hypokalaemic paralysis was made, and she was given intravenous potassium supplementation along with intravenous fluids, but her altered sensorium was still unexplained. in addition, computed tomography (ct) of brain and cerebrospinal fluid (csf) analysis were done, both were found to be normal. on further evaluation, her thyroid function test showed thyroid stimulating hormone (tsh) = 0.0056 miu/l, t3 = 28.26 pg/ml, t4 = 66.66 ng/ml, tsh receptor antibody level of 30.27 iu/l, and anti thyroperoxidase (tpo) of 1433 iu/l (table 1). thyroid scan also showed an increased radioactive iodine uptake. the final diagnosis of graves’ disease with thyroid storm and thyrotoxic hypokalaemia paralysis was made on the basis of clinical features and blood investigations. patient was immediately put on propylthiouracil (600 mg loading dose followed by 200 mg, 6 hourly), propranolol (80 mg, 8 hourly), and hydrocortisone (100 mg intravenous, 8 hourly) along with supportive care, which included cold water sponging and antipyretics. on investigating the precipitant of thyroid storm, she was found to have an abscess about 90 ml in segment vi of liver. she underwent needle aspiration of the abscess and received intravenous antibiotics (metronidazole). abscess culture was sterile. in addition, blood and urine culture were also performed to rule out other potential sources of infection, which were sterile. the patient regained full consciousness on day 3 and a repeat neurological examination revealed quadriparesis with predominant proximal muscle involvement. on day 3, her potassium level was 3.12 mmol/l which increased to 5.4 mmol/l on day 5 without further potassium supplementation suggesting rebound hyperkalaemia. at day 6 of hospitalization, her power of bilateral lower limb and upper limb improved and the patient was able to stand with support and feed herself. hydrocortisone was stopped on day 6 due to the improvement in thyroid storm. patient was continued on antibiotics in view of liver abscess for 14 days along with antithyroid drugs. on day 14 the patient was discharged in fully oriented state, with improved power of 4/5 in all limbs. the dose of propylthiouracil was further reduced (100 mg, 8 hourly), which was scheduled for tapering based on further clinical improvement. on day 30 of follow-up, repeat thyroid function showed further improvement (table 1). 3. discussion neurological involvement in hyperthyroidism is not uncommon and may present with diverse clinical features. symptoms may vary from mild features like tremors, chorea, headache, peripheral neuropathy, and hyperthyroid myopathy to life-endangering seizures, thyroid storm and thyrotoxic periodic paralysis (6). tpp as the first presenting feature of hyperthyroidism is a rare entity. another highlight of our report was thyroid storm, which was precipitated by liver abscess along with tpp. thyrotoxic periodic paralysis is a medical emergency, manifesting as paraparesis or quadriparesis mainly in the asian population suffering from hyperthyroidism. it is more commonly present in young males compared to females with a ratio of approximately 20:1 (7). clinical features of thyrotoxic periodic paralysis include recurrent attacks of muscle weakness with predominant proximal muscle involvement (8). episodes may range from prodromes (mild weakness, cramps, stiffness) to complete quadriparesis and respiratory muscle involvement (9). guillain-barre syndrome, myasthenia gravis, transverse myelitis, snake envenomation and hysterical disorder are among the common differential diagnoses of thyrotoxic hypokalaemic paralysis. unlike gbs, respiratory involvement is rare in tpp (10). in our patient, the absence of toxin exposure, lack of diurnal variation of weakness, and normal neuroimaging and csf findings ruled out the other possibilities. proposed pathogenesis behind tpp is related to ion channel defect. hypokalaemia is due to transcellular shift of potassium ion, which is controlled by na+k+ atpase pump. the activity of na+k+ atpase is mainly influenced by insulin and beta-adrenergic catecholamines. increased adrenergic state in thyrotoxicosis leads to increased activity of na+k+ atpase, which causes transcellular shift of potassium resulting in the various manifestations of hypokalaemia (3). hyperinsulinemic state, stress, infections, high carbohydrate diet, beta-2 adrenergic bronchodilators and strenuous physical activity may also act as tpp precipitants. however, precipitating factors could not be identified in nearly 34% of the cases (11). genetic mutations have been found to increase susceptibility to tpp, the most commonly noted mutation is the one affecting the gene that encodes kir2.6, an inwardly rectifying potassium channel, which is regulated by thyroid hormone (12). diagnosis involves hypokalaemia with normal acid base balance associated with suppressed tsh and raised t3 and t4 levels. the potassium levels have shown to be correlated with severity of muscle weakness; however, no correlation is seen with t3 and t4 levels (2). management of tpp includes initial supplementation of potassium along with beta-blockers and achievement of euthyroid state using anti-thyroid drugs. potassium supplementation should be gradual and under continuous potassium monitoring as total body potassium remains the same, which can cause life-threatening rebound hyperkalaemia after the achievement of euthyroid state. rebound hyperkalaemia is reported in around 50% of the cases with tpp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e19 (13). beta blockers (propranolol) have 2 mechanisms in tpp, the first one is to antagonise the adrenergic stimulation of na+k+ atpase and the second one is to decrease the peripheral conversion of t4 to t3, which is the active form. another important facet of tpp management is to mitigate the risk of paradoxical hypokalaemia, which can be seen in 25% of the patients, particularly those with late administration of antithyroid drugs and beta blockers (13). our patient also had simultaneous thyroid storm with thyrotoxic periodic paralysis. corticosteroids are useful for thyroid storm management but at the same time could precipitate tpp, which makes it even more difficult to treat. furthermore, our patient also had a liver abscess, which is an unusual trigger for thyrotoxic crisis and periodic paralysis. further large-scale studies will be needed to understand the effect of corticosteroids on the course of periodic paralysis. 4. conclusion prompt diagnosis and treatment of thyrotoxic periodic paralysis is vital to prevent fatal complications like cardiac arrhythmias. thyroid function test should be sought in every patient presenting to emergency department with hypokalaemic paralysis. 5. declarations 5.1. source of funding none. 5.2. conflict of interest the authors declare that they have no conflict of interest 5.3. authors’ contributions all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. 5.4. ethical considerations written informed consent was taken from the patient. references 1. carroll r, matfin g. endocrine and metabolic emergencies: thyroid storm. therapeutic advances in endocrinology and metabolism. 2010;1(3):139-45. 2. salih m, van kinschot c, peeters r, de herder w, duschek e, van der linden j, et al. thyrotoxic periodic paralysis: an unusual presentation of hyperthyroidism. neth j med. 2017;75(8):315-20. 3. lam l, nair rj, tingle l, editors. thyrotoxic periodic paralysis. baylor university medical center proceedings; 2006: taylor & francis. 4. abbasi b, sharif z, sprabery lr, lopez fa. hypokalemic thyrotoxic periodic paralysis with thyrotoxic psychosis and hypercapnic respiratory failure. the american journal of the medical sciences. 2010;340(2):147-53. 5. qian y-y, dai z-j, zhu c, zhu y-x, wu c-m. thyrotoxic periodic paralysis complicated by life-threatening acute hypercapnic respiratory failure in a chinese male with painless thyroiditis. the american journal of emergency medicine. 2019;37(2):379. e1-. e3. 6. stasiolek m, editor neurological symptoms and signs in thyroid disease. thyroid research; 2015: springer. 7. jandhyala sn, madireddi j, belle j, rau n, shetty r. hypokalaemic periodic paralysis–a prospective study of the underlying etiologies. journal of clinical and diagnostic research: jcdr. 2015;9(9):oc17. 8. meseeha m, parsamehr b, kissell k, attia m. thyrotoxic periodic paralysis: a case study and review of the literature. journal of community hospital internal medicine perspectives. 2017;7(2):103-6. 9. kung aw. thyrotoxic periodic paralysis: a diagnostic challenge. the journal of clinical endocrinology & metabolism. 2006;91(7):2490-5. 10. wu c-z, wu y-k, lin j-d, kuo s-w. thyrotoxic periodic paralysis complicated by acute hypercapnic respiratory failure and ventricular tachycardia. thyroid. 2008;18(12):1321-4. 11. chang c-c, cheng c-j, sung c-c, chiueh t-s, lee ch, chau t, et al. a 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants. european journal of endocrinology. 2013;169(5):529. 12. cheng c-j, lin s-h, lo y-f, yang s-s, hsu y-j, cannon sc, et al. identification and functional characterization of kir2. 6 mutations associated with non-familial hypokalemic periodic paralysis. journal of biological chemistry. 2011;286(31):27425-35. 13. shiang j-c, cheng c-j, tsai m-k, hung y-j, hsu y-j, yang s-s, et al. therapeutic analysis in chinese patients with thyrotoxic periodic paralysis over 6 years. european journal of endocrinology. 2009;161(6):911. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. banavathu et al. 4 table 1: laboratory findings of the presented case laboratory parameters patient values normal hemoglobin (g/dl) 11.1 12-15 white blood cell count (/µl) 14×103 (4-11) ×103 serum sodium (meq/l) 137 135-145 creatine kinase-mb (u/l) 25 0-24 tsh receptor antibody (iu/ml) 30.27 <1.22 anti tpo antibody (iu/ml) 1433 < 60 serum calcium (mg/dl) 9.1 8.8-10.6 serum phosphorus (mg/dl) 3.38 2.5-4.5 serum magnesium (mg/dl) 1.9 1.5-2.5 serum anion gap (mmol/l) 8 8-12 arterial blood gas analysis ph 7.40 7.35-7.45 pco2 (mmhg) 23 35-45 hco3 (mmol/l) 19.6 22-28 natrium (mmol/l) 140 potassium (mmol/l) 2.25 chloride (mmol/l) 106 urinalysis ph 7.5 urinary na (mmol/l) 157.1 40-220 urinary k (mmol/l) 14.47 <20 urinary chloride (mmol/l) 121.7 pus cells nil red blood cell nil albumin nil serum potassium (meq/l) on admission 2.23 3.5-5.1 day 5 5.14 day 7 4.2 tsh (miu/l) on admission 0.005 0.3 4.0 after 2 weeks 0.016 at 4 weeks 0.1 free t3 (pg/ml) on admission 28.26 2.2-4.2 after 2 weeks 3.2 at 4 weeks 3.82 free t4 (ng/dl) on admission 66.66 0.80-1.70 after 2 weeks 3.69 at 4 weeks 1.20 tsh: thyroid stimulating hormone; tpo: thyroperoxidase; na: natrium; k: potassium. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2017; 5 (1): e9 or i g i n a l re s e a rc h the relation of q angle and anthropometric measures with ankle sprain; a case-control study hamid zamani moghadam1, seyed taha hoseini1, amir masoud hashemian1, mohammad davood sharifi1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: april 2016; accepted: may 2016; published online: 8 january 2017 abstract: introduction: since most studies on ankle sprain are medical and sports-related and not much epidemiologic and etiologic data from the general population exist in this field, the present study evaluates the relationship between q angle and anthropometric measures with ankle sprain in the general population. methods: in the present case-control study, all of the patients over 18 years age presenting to emergency departments (ed) of two educational hospitals, complaining from ankle sprain, were evaluated during more than 1 year. a checklist consisting of demographic data, height, weight, body mass index (bmi), and history of ankle sprain, as well as degree of q angle was filled for all participants. the correlation of mentioned variables with incidence of ankle sprain was calculated using spss 22. results: 300 patients with ankle sprain were evaluated (53.5% male). mean age of the patients was 37.03 ± 14.20 years. mean weight, height, and bmi were 71.71 ± 11.26 (43 114), 168.74 ± 8.63 (143 190) and 25.14 ± 3.19 (18.41 38.95), respectively. mean q angle of the patients was 12.78 ± 3.19 degrees (5 23). there was a significant correlation between weight (p < 0.001), bmi (p = 0.001), history of sprain (r: 0.26, p < 0.001) and q angle (p = 0.002) with incidence of ankle sprain. in addition, there was a significant statistical correlation between weight (p = 0.031), bmi (p = 0.020) and q angle (p = 0.004) with history of ankle sprain. in patients with a history of ankle sprain, q angle was wider by about 2 degrees. conclusion: it seems that the prevalence of ankle sprain directly correlates with high weight, bmi, and q angle and is more prevalent in those with a history of sprain. although the findings of the present study show a statistically significant correlation between these factors and ankle sprain, the correlation is not clinically significant. keywords: ankle injuries; ankle joint; lateral ligament, ankle; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: zamani moghadam h, hoseini s t, hashemian a, sharifi m. the relation of q angle and anthropometric measures with ankle sprain; a case-control study. emergency. 2017; 5 (1): e9. 1. introduction ankle sprain is a problem caused by injury of ligaments around the ankle and has a prevalence between 5.2 6 cases in 1000 population. based on gender this rate may vary between 12.7 in 1000 for women and 0.8 in 1000 for men (1, 2). plain radiography, magnetic resonance imaging (mri), and clinical decision rules such as ottawa ankle rule are among the diagnostic tools that aid in making a diagnosis in this regard. asymmetric stretch of ankle flexor muscles, increase in body mass index (bmi), weight increase, and younger age are introduced as risk factors of ankle sprain (3, 4). many studies have mentioned q angle or quadriceps angle as an ∗corresponding author: mohammad davood sharifi; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel/fax: +989151156758; email: sharifimd@mums.ac.ir independent risk factor in increasing the probability of ankle sprain (4, 5). pefanis et al. studied 45 professional athletes and showed that there is no direct correlation between this angle and increased risk of ankle sprain (4). on the other hand, in another study the results showed the contrary and a significant correlation was found between q angle and ankle sprain in women who played in the university basketball league in america (5). since most studies on ankle sprain are medical and sports-related and not much epidemiologic and etiologic data from the general population exist in this field, the present study evaluates the relationship between q angle and anthropometric measures with ankle sprain in the general population. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. zamani moghadam et al. 2 2. methods 2.1. study design and setting in the present case-control study, all of the patients presenting to the emergency departments (ed) of imam reza and shahid hasheminezhad hospitals, mashhad, iran, complaining from ankle sprain, were evaluated during more than 1 year ( june 2014 to october 2015). the study aimed to evaluate the correlation of q angle and anthropometric measures with ankle sprain incidence. written consent was obtained from the patients before including them in the study. protocol of the study was approved by the ethics committee of mashhad university of medical sciences. to protect personal and confidential data of patient files, the researchers adhered to the principles of helsinki declaration. 2.2. participants all the patients over 18 years of age presenting to ed with complaint of ankle sprain were included using census sampling. cases with history of trauma, fracture, and defect or disability in lower extremities were excluded. in addition, patients who had obvious open or closed fracture according to plain radiography and initial physical examination results were excluded. for all patients, a checklist consisting of demographic data, such as age, sex, height, weight, calculation of body mass index (bmi: weight/height2) and history of ankle sprain, was filled. then q angle was calculated and recorded for all the participants. an equal number of patients over 18 years old who presented to the hospital due to reasons other than trauma and lower extremity injury were included as the control group if they gave their consent. 2.3. q angle measurement to calculate q angle, anatomic points of anterior superior iliac spine, middle patellar point, tibial tuberosity while standing, without shoes and in the right lower extremity were used. the angle between the line that connects anterior superior iliac spine to middle patellar point and the line that connects tibial tuberosity to middle patellar point was considered as q angle and was measured twice to increase accuracy. standard goniometer was used for measuring the angle. the center of the goniometer was positioned on the center of patella, its long arm parallel to or on the lateral mid line of pelvis, and the short arm on the tibial tubercle, the resulting angle was recorded. mean of the 2 q angle measurements were used for each patient. all the steps were done by a trained senior emergency medicine resident. figure 1 shows q angle measurement using romberg method. figure 1: romberg method of measuring q angle. 2.4. statistical analysis census sampling was used in the present study and therefore all the patients with complaint of ankle sprain who visited the ed of the mentioned hospitals during the study period were included. statistical analysis of the data was done using spss version 22. mean and standard deviation (sd) were used to report the quantitative data and frequency and percentage were used for reporting qualitative ones. after making sure that the data had normal distribution, chi-squared and t-test were applied to compare the case and control groups. correlations were calculated using pearson’s r for categorical variables and spearman correlation for continuous ones. p value < 0.05 was considered significant. 3. results: 300 patients with ankle sprain were evaluated (53.5% male). mean age of the patients was 37.03 ± 14.20 years (range: 18 82) with the highest frequency in the 26 30 age group. mean weight, height, and bmi were 71.71 ± 11.26 (43 114), 168.74 ± 8.63 (143 190) and 25.14 ± 3.19 (18.41 38.95), respectively. mean q angle of the patients was 12.78 ± 3.19 degrees (5 23). there was a significant correlation between weight (r: 0.127; p < 0.001), bmi (r: 0.130; p = 0.001), history of sprain this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e9 table 1: comparison of the case and control groups characteristics variable case group control group p value age (years) 37.02 ± 14.16 37.03 ± 14.26 0.993 weight (kg) 73.32 ± 11.83 70.09 ± 0.43 < 0.001 height (cm) 169.20 ± 8.38 168.28 ± 8.86 0.189 body mass index 25.56 ± 3.39 24.72 ± 2.93 0.001 q angle 13.18 ± 3.77 12.37 ± 2.41 0.002 sex male 160 (53.3) 161 (53.7) 0.5 female 140 (46.7) 139 (46.2) history of sprain 42 (14) 1 (0.3) < 0.001 data are shown as mean and standard deviation or frequency and percentage. table 2: comparison of weight, height, body mass index, q angle and gender with history of ankle sprain variable history of sprain no history of sprain p value age (years) 35.63 ± 13.00 37.13 ± 14.29 0.185 weight (kg) 75.28 ± 12.76 71.43 ± 11.01 0.031 height (cm) 169.14 ± 9.13 168.71 ± 8.60 0.753 body mass index 26.24 ± 3.30 25.03 ± 3.17 0.020 q angle 14.14 ± 3.30 12.67 ± 3.13 0.004 sex male 22 (6.9) 299 (93.1) 0.435 female 21 (7.5) 258 (92.5) data are shown as mean and standard deviation or frequency and percentage. (r: 0.265; p < 0.001) and q angle (r: 0.091; p = 0.002) with incidence of ankle sprain (table 1). in addition, there was a significant correlation between weight (r: 0.084; p = 0.031), bmi (r: 0.113; p = 0.020) and q angle (r: 0.107; p = 0.004) with history of ankle sprain. in patients with a history of ankle sprain, q angle was wider by about 2 degrees (table 2). 4. discussion: based on the findings of this study, it seems that ankle sprain is more prevalent in heavy people with higher bmi and q angle as well as those with a history of ankle sprain. there was a significant statistical correlation between weight, bmi, and q angle with ankle sprain. however, this significant statistical correlation was not clinically significant. ankle sprain incidence has been estimated to be 2 in 1000 cases with significant difference between genders. in ages between 15 24 years the incidence is higher in males (1.62 vs 1.41), while the rate is higher in females (2.3 vs 1.65) at the age of 30. about 50% of ankle sprain cases have been reported while doing sports with 41% in basketball players and 9.3% in football players (6). in a study on female basketball players in america, a significant correlation was found between q angle and ankle sprain, which is in line with the findings of the present study (5). in another study, a significant correlation was found between the anatomic status of ankle joint and prevalence of sprain (7). in addition, in professional football players asymmetric stretch of ankle, bmi, and gaining weight were found to be affecting ankle sprain incidence. old age and asymmetric stretch of ankle ligaments have been factors resulting in poor improvement. however, young people are more at risk of ankle sprain (3). hagglund et al. showed that despite the history of hamstring and knee injuries increasing the risk of being injured again by 3 to 4 times, history of ankle sprain does not increase the risk of it happening again (8). generalized joint laxity, ankle ligament fixation, and ankle stretch rate were highly related to ankle sprain incidence (9). in general, factors that cause an unbalance in pressure on the joints of lower extremities lead to injuries such as sprain and stretch in the joints of this region. q angle is responsible for transmitting pressure from pelvis to legs and has been estimated to be about 10 degrees in men and 15 degrees in women. if this angle deviates from its normal position, in addition to causing disorders in patellofemoral function (including patellofemoral pain, and patellar imbalance), it may be a risk factor for ankle injuries. by using preventive measures to avoid ankle stretch (such as wearing shoes with ankle support) we may be able to avoid sprain. activity level of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. zamani moghadam et al. 4 the participants, their occupation, race, and factors affecting muscular strength or tendon and joint stability were among the confounding factors of this study that should be evaluated in future studies along with other effective factors in ankle, knee and pelvis regions. 5. limitations: small sample size and not considering all probable risk factors of ankle sprain were among the most important limitations of the present study. 6. conclusion: it seems that the prevalence of ankle sprain directly correlates with high weight, bmi, and q angle and is more prevalent in those with a history of sprain. although the findings of the present study show a statistically significant correlation between these factors and ankle sprain, the correlation is not clinically significant. 7. appendix 7.1. acknowledgements the authors wish to thank the emergency department staff of imam reza and shahid hasheminezhad hospitals, mashhad, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none 7.4. funding none references 1. bridgman s, clement d, downing a, walley g, phair i, maffulli n. population based epidemiology of ankle sprains attending accident and emergency units in the west midlands of england, and a survey of uk practice for severe ankle sprains. emergency medicine journal. 2003;20(6):508-10. 2. wilson t, kitsell f. is the q-angle an absolute or a variable measure?: measurement of the q-angle over one minute in healthy subjects. physiotherapy. 2002;88(5):296-302. 3. fousekis k, tsepis e, vagenas g. intrinsic risk factors of noncontact ankle sprains in soccer a prospective study on 100 professional players. the american journal of sports medicine. 2012;40(8):1842-50. 4. pefanis n, papaharalampous x, tsiganos g, papadakou e, baltopoulos p. the effect of q angle on ankle sprain occurrence. foot & ankle specialist. 2009;2(1):22-6. 5. steinberg rje, picconatto w. q-angle: does it increase risk of ankle sprains in ncaa division iii women’s basketball?: 1879: board# 167 10: 30 am-10: 30 am. medicine & science in sports & exercise. 2007;39(5):s318-s9. 6. waterman br, owens bd, davey s, zacchilli ma, belmont pj. the epidemiology of ankle sprains in the united states. j bone joint surg am. 2010;92(13):2279-84. 7. beynnon bd, murphy df, alosa dm. predictive factors for lateral ankle sprains: a literature review. journal of athletic training. 2002;37(4):376. 8. hagglund m, walden m, ekstrand j. previous injury as a risk factor for injury in elite football: a prospective study over two consecutive seasons. british journal of sports medicine. 2006;40(9):767-72. 9. baumhauer jf, alosa dm, renstrom pa, trevino s, beynnon b. a prospective study of ankle injury risk factors. the american journal of sports medicine. 1995;23(5):564-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 170 emergency (2014); 2 (4): 170-173 original research potential risk factors of death in multiple trauma patients sina jelodar, peyman jafari, mahnaz yadollahi, golnar sabetian jahromi, hoseynali khalili, hamidreza abbasi, shahram bolandparvaz, shahram paydar* trauma research center, shiraz university of medical sciences, shiraz, iran abstract introduction: trauma has been recognized as one of the leading causes of death in many countries for decades. reduction in mortality and morbidity rate of trauma cases is one of the most important attitudes in this field. evaluation of different risk factors have been considered as the main goal of some studies. the purpose of this study was determining potential risk factors of death in trauma patients. method: in a retrograde study, data of 740 patients admitted during three years (2009-2011) were studied. demographic data (sex and age), clinical factors (blood pressure, pulse rate, respiratory rate, glasgow coma scale (gcs)), trauma characteristics (location, type of injury, etc.), as well as outcome of patients were evaluated. data analyses was done using spss 18.0. stepwise multivariate regression analysis was used for recognition of independent predictive factors of death in multiple trauma patients. results: of those admitted, majority of patients were male (81.4%), 68% between 18 to 60 years, and 11.2% of them died during the course of treatment. age; type of trauma; abnormal respiration rate, pulse rate, blood pressure; total gcs ≤8; abnormal pupil size; and head and neck; vertebral, and extremities fractures were obtained as significant predictive factor of death. gcs≤8, head and neck fracture, and abnormal pulse rate were independent death predictors. conclusion: we identified gcs≤8, head and neck fracture, and abnormal pulse rate as predictive factors of mortality after trauma, which remained independent in the presence of all other factors and potentially treatable. key words: risk factors; mortality; death; multiple trauma cite this article as: jelodar s, jafari p, yadollahi m, et al. potential risk factors of death in multiple trauma patients. emergency. 2014;2(4):170-3. introduction: 1 rauma has been recognized as one of the responsible causes of death and disability in the world for decades (1-4). in 1966, national research council published a book entitled ‘‘accidental death and disability the neglected disease of modern society’’ which attracted a great deal of attention towards the high rate of mortality among trauma patients (5). identification of variants that lead to death after trauma has been addressed by many researchers (6-9). macleod and colleagues concluded that low hemoglobin, elevated prothrombin time (pt), partial thromboplastin time (ptt), and elevated base deficit were prognostic indicators which remained independent and potentially treatable among all causes of mortality after trauma(6). on the other hand, head injury, increasing age, and injury severity score (iss) were found as independent untreatable indicators of mortality (6, 10). it is clear that reduce in mortality and morbidity rate of trauma is a bilateral function from people and educated medical staff (11-16). it may be concluded that except immediate deaths, many death predictors are controllable or *corresponding author: shahram paydar; trauma research center, shahid rajaei trauma hospital, shahid chamran blvd, shiraz, iran. tel/fax: +987116254206; email: paydarsh@gmail.com received: july 2014; accepted: august 2014 treatable at the scene by passing pedestrians or the paramedics to keep the patient alive until he or she arrives at the emergency department (17). the aim of this study was to identify independent risk factors of death in trauma patients. methods: study design and setting: current retrograde cross-sectional study was carried out on documents of patients admitted to the emergency department of rajaee hospital, shiraz, iran, through 2009-2011. study protocol was approved by ethics committee of shiraz university of medical sciences. subjects: the patients older than 18 years old and younger than 80 were enrolled. inclusion criteria consisted of injury severity score (iss) > 9, change in hemodynamic of patients, and more than one simultaneous injury. pregnant women, assaults, burn >20% body surface area, dead on arrival, diabetic patients, and transferred out to another institution were excluded. the minimum sample size for the study was equal to 342 cases, with an odds ratio (or) of 4.0 for glasgow comma scale (gcs) ≤9 and prevalence of 6.3% mortality in trauma patients (18), at the significance level of 5% (one-sided test) and power of 90%. finally, 740 patients were enrolled to t mailto:paydarsh@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 171 jelodar et al the study based on simple random sampling and using a random number table. variables demographic data (sex and age), clinical factors (blood pressure, pulse rate, respiratory rate, pupil size, gcs), trauma characteristics (location, type of injury, etc.), as well as outcomes of patients were evaluated. the outcome was defined as death or viability. an outcome variable, “death,” was considered if the patient had either an emergency room result of “death” or a hospital result of “expired.” statistical analysis statistical analysis was performed using spss version 13.0. categorical data were compared using chisquared or fisher’s exact test. variables that were established as mortality predictors in univariate analysis, were entered to a stepwise logistic regression to determine independent predictive variables of mortality. data were presented as or and 95% confidence interval (95% ci). p values <0.05 were statistically considered significant. results: seven hundred forty patients were enrolled (81.4% male). the mean age of patients was 34.62± 5.75 years (range: 18-80). eighty-three (11.2%) patients were died during the course of treatment. after performing the table1: relationship between demographic and clinical factors and death in studied patients variable alive (%) death (%) p-value age <60 456 (95.4) 22 (4.6) 0.001 ≥60 199 (88.4) 26 (11.6) gender male 467 (93.4) 33 (6.6) 0.38 female 109 (95.6) 5 (4.4) respiratory rate normal 330 (85.4) 56 (14.5) 0.002 abnormal 295 (92.8) 23 (7.2) type of accident motor vehicle accident 606 (89.6) 70 (10.4) <0.001 fall 50 (86.2) 8 (13.8) other 1 (16.7) 5 (83.3) pulse rate normal 173 (80.5) 42 (19.5) <0.001 abnormal 451 (95.2) 38 (7.8) blood pressure normal 394 (92.3) 33 (7.7) <0.001 abnormal 257 (84.0) 49 (16.0) glasgow comma scale >8 553 (95.2) 28 (4.8) <0.001 ≤8 54 (51.9) 50 (48.1) pupil size normal 126 (79.8) 32 (20.5) <0.001 abnormal 6 (31.6) 13 (68.4) head and neck fracture no 624 (90.7) 64 (9.3) <0.001 yes 33 (63.5) 19 (36.5) thoracic injury no 530 (88.5) 69 (11.5) 0.6 yes 127 (90.1) 14 (9.9) vertebral fracture no 602 (88.1) 81 (11.9) 0.05 yes 55 (96.5) 2 (3.5) abdominal injury no 569 (86.6) 74 (89.2) 0.74 yes 88 (90.7) 9 (9.3) pelvic fracture no 609 (88.9) 76 (11.1) 0.71 yes 48 (87.3) 7 (12.7) extremities fracture no 327 (85.6) 55 (14.4) 0.005 yes 330 (92.2) 28 (7.8) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 172 emergency (2014); 2 (4): 170-173 univariate analysis, age> 60 years (p=0.001), type of trauma (p<0.001), abnormal respiration rate (p=0.001), abnormal pulse rate (p<0.001), abnormal blood pressure e (p<0.001), total gcs <8 (p<0.001), abnormal pupil size (p<0.001), head and neck fracture (p<0.001), vertebral fracture (p=0.05), and extremities fracture (p=0.005) were identified as the potential predictive factors of death (table 1). the results of stepwise multivariate logistic regression analysis were summarized in table 2. based on the results, only three varia bles remained as independent predictors of death. these variants were total gcs belo w 8 (or=16.5; 95% ci: 5.940.8; p<0.001), presence of head and neck fracture (or=5.8; 95% ci: 3.1-9.5; p<0.001), and abnormal pulse rate (or=5.7; 95% ci: 1.9-17.5; p<0.001). discussion: this study was performed in order to find the independent predictors of death in trauma cases. in the current study gcs below 8 beside presence of head and neck fracture as well as abnormal pulse rate have been recognized as independent predictors of death in trauma patients. evaluation of demographic and clinical factors are crucial in management of trauma victims because of its effect on mortality rate. lichtveld et al. in 2007 showed age, presence of isolated neurological damage, base excess, and hemoglobin as death risk factors. they also reported that severe head injuries and hemorrhage as the most important risk factors of death in the first 24 hours after the accident (19, 20). kuhls et al. showed age and gcs yields higher discriminatory power in mortality prediction in trauma (21). probst c et al. categorized risk factors in treatable and untreatable indicators of mortality groups, and mentioned head injury, increasing age, and injury severity score (iss) in the second group (10). the incidence of coagulation abnormalities, early after trauma, was considered also as independent predictors of mortality even in the presence of other risk factors (22). since death has a significant correlation with ages younger than 60, the victim’s age should always be considered as a death predictor. however, normal vital sign in a primary evaluation should not persuade the examiner and more rapid evaluations should be performed. a study found the mortality rate for all grades of injury was about 10% higher in the 70 years and older ages when compared to the 20 to 70 years (23). our analysis showed a significant correlation between age, respiratory rate, blood pressure, pulse rate, head and neck fractures, vertebral fracture, extremity fracture, and gcs with death after trauma. a high iss (≥ 30), post-injury gcs status, and hemodynamic function can affect elderly trauma mortality (24). multivariate analysis using mixed effect logistic regression was applied and adjusted for age, gender, iss and gcs to overcome their confounding effect on mortality rates (25). since the majority of deaths occur due to brain damage (i.e. decrease in gcs score) or neck rather than multi organ failures, the trauma team must be cautious and well trained to reduce the unwanted iatrogenic damages in these vital organs (26). this study confirmed the association of head and neck fracture with death (p<0.001). it is clear that an eligible and reliable treatment protocol such as atls is an important factor to reduce the mortality and morbidity of the patient with multiple traumas (16, 21). findings revealed that mortality rate of trauma victims can be reduced only with a focused primary survey and an efficient treatment plan, as well as proper use of resources. conclusion: we identified gcs below 8, head and neck fracture, and abnormal pulse rate as predictive factors of mortality after trauma, remained independent in the presence of all other factors and potentially treatable. additionally, the results showed the association of age<60, type of trauma, abnormal respiration rate, abnormal pulse rate, abnormal blood pressure, total gcs <8, abnormal pupil size, head and neck fracture, vertebral fracture, and extremities fracture with death in trauma patients. acknowledgments: we would like to say thank to all the emergency department staffs of imam khomeini hospital, sari, iran. conflict of interest: none funding support: none authors’ contributions: all authors participated in the study concept and design, acquisition of data, data analysis, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. references: 1. lopez ad, mathers cd, ezzati m, jamison dt, murray cj. global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. the lancet. 2006;367(9524):1747-57. 2. world health organization. injury: a leading cause of the global burden of disease 2000: who: geneva; 2011. 4-15 p. 3. jayaraman s, sethi d. advanced trauma life support training for hospital staff. cochrane database syst rev. 2009;2(3):cd004173. 4. murray cj, lopez ad. global mortality, disability, and the table 2: independent predictors of death in studied patients predictive factor or 95% ci p gcs ≤8 16.5 5.9-40.8 <0.001 head and neck fracture 5.8 3.1-9.5 <0.001 abnormal pulse rate 5.7 1.9-17.5 0.002 or: odds ratio ci: confidence interval http://www.ncbi.nlm.nih.gov/pubmed?term=probst%20c%5bauthor%5d&cauthor=true&cauthor_uid=19359940 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 173 jelodar et al contribution of risk factors: global burden of disease study. the lancet. 1997;349(9063):1436-42. 5. national academy of s, national research council committee on t, national academy of s, national research council committee on s. accidental death and disability: the neglected disease of modern society. washington (dc): national academies press (us); 1966. p. 1-39. 6. macleod j, lynn m, mckenney mg, jeroukhimov i, cohn sm. predictors of mortality in trauma patients. american surgeon. 2004;70(9):805-10. 7. alimohammadi h, bidarizerehpoosh f, mirmohammadi f, et al. cause of emergency department mortality: a case-control study. emergency. 2014;2(1):30-5. 8. paydar s, moghaninasab a, asiaei e, jahromi gsf, bolandparvaz s, abbasi h. outcome of patients underwent emergency department thoracotomy and its predictive factors. emergency. 2014;2(3):125-9. 9. rao d, sood d, pathak p, dongre sd. cause of sudden cardiac deaths on autopsy findings; a four-year report. emergency. 2014;2(1):12-7. 10. probst c, zelle ba, sittaro na, lohse r, krettek c, pape hc. late death after multiple severe trauma: when does it occur and what are the causes? j trauma. 2009;66(4):1212-7. 11. carley s, driscoll p. trauma education. resuscitation. 2001;48(1):47-56. 12. ip aow hh. trauma service in queen elizabeth hospital. emergi-news. 2000;11(2):7-10. 13. lau pf lc. a brief introduction of the trauma care system in pyneh. emergi-news. 2000;11(1):4-5. 14. kesinger mr, nagy lr, sequeira dj, charry jd, puyana jc, rubiano am. a standardized trauma care protocol decreased in-hospital mortality of patients with severe traumatic brain injury at a teaching hospital in a middle-income country. injury. 2014;45(9):1350-4. 15. dagal a, greer se, mccunn m. international disparities in trauma care. current opinion in anesthesiology. 2014;27(2):233-9. 16. bidgoli hh, bogg l, hasselberg m. pre-hospital trauma care resources for road traffic injuries in a middle-income country—a province based study on need and access in iran. injury. 2011;42(9):879-84. 17. eckstein m, chan l, schneir a, palmer r. effect of prehospital advanced life support on outcomes of major trauma patients. j trauma. 2000;48(4):643-8. 18. hampton da, lee th, diggs bs, mccully sp, schreiber ma. a predictive model of early mortality in trauma patients. american journal of surgery. 2014;207(5):642-7. 19. lichtveld ra, panhuizen if, smit rb, holtslag hr, van der werken c. predictors of death in trauma patients who are alive on arrival at hospital. european journal of trauma and emergency surgery. 2007;33(1):46-51. 20. perdue pw, watts dd, kaufmann cr, trask al. differences in mortality between elderly and younger adult trauma patients: geriatric status increases risk of delayed death. j trauma. 1998;45(4):805-10. 21. kuhls da, malone dl, mccarter rj, napolitano lm. predictors of mortality in adult trauma patients: the physiologic trauma score is equivalent to the trauma and injury severity score. journal of the american college of surgeons. 2002;194(6):695-704. 22. macleod jb, lynn m, mckenney mg, cohn sm, murtha m. early coagulopathy predicts mortality in trauma. j trauma. 2003;55(1):39-44. 23. mccoy g, johnstone r, duthie r. injury to the elderly in road traffic accidents. j trauma. 1989;29(4):494-7. 24. chang w-h, tsai s-h, su y-j, huang c-h, chang k-s, tsai ch. trauma mortality factors in the elderly population. int j gerontol. 2008;2(1):11-7. 25. hasler rm, nuesch e, jüni p, bouamra o, exadaktylos ak, lecky f. systolic blood pressure below 110 mmhg is associated with increased mortality in blunt major trauma patients: multicentre cohort study. resuscitation. 2011;82(9):1202-7. 26. ghajar j. traumatic brain injury. the lancet. 2000;356(9233):923-9. emergency. 2017; 5 (1): e8 or i g i n a l re s e a rc h potential child abuse screening in emergency department; a diagnostic accuracy study hossein dinpanah1, abazar akbarzadeh pasha2∗, mojtaba sanji3 1. emergency department, shahid beheshti hospital, babol university of medical sciences, babol, iran. 2. urology department, shahid beheshti hospital, babol university of medical sciences, babol, iran. 3. emergency department, ali ebne abitaleb hospital, rafsanjan university of medical sciences, rafsanjan, iran. received: march 2016; accepted: may 2016; published online: 8 january 2017 abstract: introduction: designing a tool that can differentiate those at risk of child abuse with great diagnostic accuracy is of great interest. the present study was designed to evaluate the diagnostic accuracy of escape instrument in triage of at risk cases of child abuse presenting to emergency department (ed). methods: the present diagnostic accuracy study performed on 6120 of the children under 16 years old presented to ed during 3 years, using convenience sampling. confirmation by the child abuse team (pediatrician, a social worker, and a forensic physician) was considered as the gold standard. screening performance characteristics of escape were calculated using stata 21. results: 6120 children with the mean age of 2.19 ± 1.12 years were screened (52.7% girls). 137 children were suspected victims of child abuse. based on child abuse team opinion, 35 (0.5%) children were confirmed victims of child abuse. sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive values of this test with 95% ci were 100 (87.6 – 100), 98.3 (97.9 – 98.6), 25.5 (18.6 – 33.8), 100 (99.9 – 100), 0.34 (0.25 – 0.46), and 0 (0 – nan), respectively. area under the roc curve was 99.2 (98.9 – 99.4). conclusion: it seems that escape is a suitable screening instrument for detection of at risk cases of child abuse presenting to ed. based on the results of the present study, the accuracy of this screening tool is 99.2%, which is in the excellent range. keywords: child abuse; diagnosis; emergency service, hospital; risk assessment; decision support techniques © copyright (2017) shahid beheshti university of medical sciences cite this article as: dinpanah h, akbarzadeh pasha a, mojtaba sanji. potential child abuse screening in emergency department; a diagnostic accuracy study. emergency. 2017; 5 (1): e8. 1. introduction non-accidental physical, mental, emotional or sexual abuse, or neglect of children under 18 years of age, which endangers the child’s health, comfort, and education, is defined as child abuse (1). regardless of the culture and beliefs of a society, mistreating children may be a major health problem that requires attention from the governments and health care systems due to its wide range of long term effects. it may seem like a personal problem at first sight, however considering its probable side effects such as depression, borderline personality disorder, multiple personality disorder, attention deficit disorder, drug and alcohol abuse, prostitution, ∗corresponding author: abazar akbarzadeh pasha; urology department, shahid beheshti hospital, keshvari square, babol, iran. tel/fax: 00989111112231; email: aapash812@yahoo.com running away from home, antisocial and criminal behavior, and sexual crimes, it is considered a social and multidimensional phenomenon (2). child abuse was first assessed as a problem that may affect the present and future life of a person in 1962 with publication of an article titled “the beaten child syndrome”, which became a stepping-stone for future studies (3). according to statistics, during 1976 to 1983 more than 50000 children were killed by their parents as a result of child abuse in the united states, and more than 25 million children were subject to abuse and anger (4). in 1995, more than 3 million children were referred to child support centers in the united states due to abuse and neglect. death or sickness of a family member, financial problems and dissatisfaction with marriage, have been introduced as child abuse risk factors (5). in iran, most cases of child abuse belong to physical abuse of boys and factors such as parents low educational level, low economic status, populated family, and mental and physical illnesses are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. dinpanah et al. 2 identified risk factors (6, 7). potential child abuse screening in those presenting to emergency department (ed) can help identify effective factors in abuse incidence and move toward reducing its prevalence by proper intervention. designing a tool that can differentiate those at risk of child abuse with great diagnostic accuracy is of great interest for emergency physicians. although in recent years, child abuse screening tools have significantly helped emergency physicians, the accuracy of these tools is still a matter of question (8-11). therefore, the present study was designed to evaluate the diagnostic accuracy of escape instrument in triage of at risk cases of child abuse presenting to ed. 2. methods 2.1. study design and setting the present study is a prospective diagnostic accuracy study performed on children presented to ed of shahid beheshti and amir kola hospitals, babol, mazandaran, iran, during 2011 to 2014. the aim of this study was evaluating the accuracy of escape tool in screening children at risk of child abuse. the study was approved by the ethics committee of babol university of medical sciences. the researchers adhered to the principles of helsinki declaration and keeping patient information confidential at all stages during the study. the patients or their relatives were assured that their personal data will be confidential and only used for the purpose of the study and written informed consent was obtained from them. 2.2. participants 6120 of the children (under 16 years old) presented to ed during the study period were triaged and enrolled using convenience sampling. inclusion criteria were consent for participation, cooperation in filling out the questionnaire, and stable clinical and hemodynamic status. cases of suicide injury, poisoning, and those who had introduced their case as child abuse or were injured by their peers were excluded. 2.3. data gathering on admission to ed, demographic data of all children (age, sex, place of living) as well as their hydration status were recorded and escape questionnaire for potential child abuse screening (appendix 1) was filled for them by asking questions from the child or the guardians (11). triage was done by trained nurses. in cases of one or more abnormal answer to the questions, the screening result was considered positive. after admission to ed, standard treatment (based on the reason for admission) was initiated and a trained emergency medicine specialist, blind to results of screening, accurately examined the child and recorded the history regarding child abuse. in cases that were diagnosed as child abuse, the child was re-examined by the hospital’s child abuse team including a pediatrician, a social worker, and a forensic physician to confirm diagnosis. emergency physician and all members of child abuse team were blind to the results of screening. confirmation by the mentioned team was considered as the gold standard for identifying the patient as a victim of child abuse. 2 emergency medicine specialists passed three 2-hour educational courses with the hospital child abuse team and were responsible for initial evaluation of the patients on admission. in-charge triage nurses in this study also underwent training for a few sessions to learn about filling the questionnaire. the validity and reliability of the questionnaire were confirmed in a previous study (11). 2.4. statistical analysis minimum sample size required for the present study was calculated to be 2696 cases, considering 2.3% prevalence of child abuse (11), 80% sensitivity, 95% confidence interval (ci), desired precision (d = 0.1). data were analyzed using stata 11.0. quantitative variables were reported as mean and standard deviation (sd) and qualitative ones were shown as frequency and percentage. to calculate the accuracy of the tool, sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values and area under the receiver operating characteristic (roc) curve were calculated with 95% ci. 3. results: 6120 children with the mean age of 2.19 ± 1.12 years were screened regarding potential child abuse (52% girls). figure 1 shows the frequency of patients in each age group. 4376 (71.5%) of the participants resided in cities. table 1 shows the frequency of positive answer to each of the 6 questions as well as their screening performance characteristics. based on the results obtained from the screening questionnaire, 137 children were suspected victims of child abuse, 120 (2%) of which had 1 positive answer, 4 (0.1%) had 2 positive answers, 1 (0.01%) had 3 positive answers, and 1 (0.01%) had 4 positive answers. finally, based on child abuse team opinion (the gold standard), 35 (0.5%) children were victims of child abuse. sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive values of this test with 95% ci were 100 (87.6 – 100), 98.3 (97.9 – 98.6), 25.5 (18.6 – 33.8), 100 (99.9 – 100), 0.34 (0.25 – 0.46), and 0 (0 – nan), respectively. figure 2 shows the area under the roc curve for the studied instrument. area under the roc curve was 99.2 (98.9 – 99.4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e8 appendix 1: escape questionnaire for screening child abuse 1. is the history consistent? yes no 2. was seeking medical help unnecessarily delayed? yes no 3. does the onset of the injury fit with the development level of the child? yes no 4. is the behavior of the child, his or her care givers and their interaction appropriate? yes no 5. are findings of the head-totoe examination in accordance with the history? yes no 6. are there signals that make you doubt the safety of the child or other family members? yes no *if yes describe the signals in the box other comments below. other comments table 1: screening performance characteristics of the child abuse questionnaire with 95% confidence interval in prediction of at risk children presented to emergency department question number (%) sensitivity specificity ppv npv 1 14 (0.2) 11.4 (0.03 – 0.27) 99.8 (99.7 – 99.9) 28.5 (0.09 – 0.57) 99.5 (99.3 – 99.6) 2 26 (0.4) 20 (9 – 40) 99.7 (99.5 – 99.8) 26.9 (12.4 – 48.0) 99.5 (99.3 – 99.6) 3 38 (0.6) 14.2 (5.3 – 31.0) 99.4 (99.2 – 99.6) 13.1 (4.9 – 28.8) 99.5 (99.2 – 99.6) 4 27 (0.4) 17.1 (7.1 – 34.2) 99.6 (99.4 – 99.7) 22.2 (9.3 – 42.7) 99.5 (99.3 – 99.6) 5 12 (0.2) 11.4 (3.7 – 27.6) 99.8 (99.7 – 99.9) 33.3 (11.2 – 64.5) 99.4 (99.2 – 99.6) 6 18 (0.3) 14.2 (5.3 – 31.0) 99.7 (99.6 – 99.8) 27.7 (10.7 – 53.5) 99.5 (99.2 – 99.6) ppv: positive predictive value; npv: negative predictive value. figure 1: age distribution of the studied children. 4. discussion: based on the findings of this study, escape screening instrument has high sensitivity and specificity in identifying potential child abuse cases presented to ed. area under the roc curve of 99.2 indicates the high accuracy of the test in this regard. as mentioned before, child abuse is a mental and health problem in every society, which is directly related to mental and physical health of the next generation. based on the statistics reported by world health organization (who) about 3 million children are maltreated around the world each year and 31000 cases of murder have been reported in children under 15 years old in 2002 alone (12). since a large figure 2: area under the roc curve of the child abuse questionnaire. number of children with various injuries are presented to ed daily, timely identification and evaluation of those suffering from or at risk of child abuse plays a significant role in preventing further damages. child abuse rate reported in various studies carried out in eds has ranged from 2% to 10% (13-19). using a standard tool that can accurately determine true cases is a challenge for physicians in supporting children’s rights. protocols designed for this purpose should be able to guide the physicians toward a comprehensive answer with few questions. in 2012, louwers et al. used escape screening instrument in 3 health centers for the first time. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. dinpanah et al. 4 in that study, escape was used to evaluate potential risk of child abuse in children (aged 0 to 18 years) presented to the eds. using this instrument, screening rate increased from 20% in february 2008 to 67% in december 2009. detection rate in the screened children was 5 times higher than those not screened. therefore, it seems that escape tool is effective in increasing detection of potential child abuse (20). pless et al. studied the accidentsuspected child abuse and neglect (a-scan) method, a checklist with 10 questions for assessing the risk of child abuse. the results of this checklist correlated with physical examination results reported by the physician. no significant increase in detection of child abuse was seen after introduction of this method. this could mean that ed staff were already doing well and the method used was not efficient (19). in another study to assess child abuse by consulting the child protection register, a flowchart with 4 questions was included in the patient’s file. results showed that inclusion of a flowchart improved awareness, attention and documentation of suspected abuse cases (15). in bleeker et al. study, a 9-question checklist was used in ed for collecting information from children suspected to be child abuse cases, which using this tool the number of detected cases increased (21). hosseinkhani and colleagues determined the status of child abuse in the iranian population and evaluated the validity and reliability of a new questionnaire. they concluded that, their questionnaire is a new tool with acceptable validity and reliability and can be applied in child abuse studies in iran (22). since currently there is no accepted standard for screening children at risk of child abuse in ed, researchers are trying to design and develop new decision rules or validate the existing tools. therefore, the present study was designed with the same aim. it seems that carrying out similar studies in other parts of the country with various cultural and economic statuses can provide more acceptable results for reaching a decision regarding the accuracy of this tool. 5. conclusion: it seems that escape is a suitable screening instrument for detection of at risk cases of child abuse presenting to ed. based on the results of the present study, the accuracy of this screening tool is 99.2%, which is in the excellent range. 6. appendix 6.1. acknowledgements all authors would like to thank all the ed staff of shahid beheshti and amir kola hospitals, babol, mazandaran, iran. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interest none 6.4. funding none references 1. http://www.who.int/topics/child_abuse/en/. 2007. 2. hobbs cj, hanks hg, wynne jm. child abuse and neglect: a clinician’s handbook: elsevier health sciences; 1999. 3. kemp a. abuse in the family: an introduction: wadsworth publishing company; 1998. 4. ludwig s, kornberg ae. child abuse: a medical reference: churchill livingstone new york; 1992. 5. mcmillan ja, feigin rd, deangelis c, jones md. oski’s pediatrics: principles & practice: lippincott williams & wilkins; 2006. 6. sayyari aa, bagheri yazdi sa, jalili b, khoshabi k, shahmohammadi d, imanzadeh f, et al. physical childabuse in tehran, iran. journal of rehabilitation (uwrs). 2002;6(6-7):7-13. 7. farhoudian a, izadian es, goodarzi rr, sharifi v, mohammadi m-r, nejatisafa a-a, et al. iran’s contribution to child and adolescent mental healthresearch (1973– 2002): a 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american journal of public health. 1985;75(1):5660. 14. hussey jm, chang jj, kotch jb. child maltreatment in the united states: prevalence, risk factors, and adolescent this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e8 health consequences. pediatrics. 2006;118(3):933-42. 15. benger jr, pearce av. quality improvement report: simple intervention to improve detection of child abuse in emergency departments. bmj: british medical journal. 2002:780-2. 16. chang dc, knight v, ziegfeld s, haider a, warfield d, paidas c. the tip of the iceberg for child abuse: the critical roles of the pediatric trauma service and its registry. journal of trauma and acute care surgery. 2004;57(6):1189-98. 17. holter jc, friedman sb. child abuse: early case finding in the emergency department. pediatrics. 1968;42(1):12838. 18. kempe ch, silverman fn, steele bf, droegemueller w, silver hk. the battered-child syndrome. jama. 1984;251(24):3288-94. 19. pless ib, sibald a, smith ma, russell m. a reappraisal of the frequency of child abuse seen in pediatric emergency rooms. child abuse & neglect. 1987;11(2):193-200. 20. louwers ec, korfage ij, affourtit mj, scheewe dj, van de merwe mh, vooijs-moulaert a-fs, et al. effects of systematic screening and detection of child abuse in emergency departments. pediatrics. 2012;130(3):457-64. 21. bleeker g, vet nj, haumann tj, van wijk ij, gemke rj. [increase in the number of reported cases of child abuse following adoption of a structured approach in the vu medical centre, amsterdam, in the period 2001-2004]. nederlands tijdschrift voor geneeskunde. 2005;149(29):1620-4. 22. hosseinkhani z, nedjat s, majdzadeh r, mahram m, aflatooni a. design of the child abuse questionnaire in iran. journal of school of public health and institute of public health research. 2014;11(3):29-38. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references emergency. 2017; 5 (1): e12 or i g i n a l re s e a rc h pain management via ultrasound-guided nerve block in emergency department; a case series study amir nejat1, houman teymourian2∗, leili behrooz1, gholamreza mohseni2 1. emergency medicine department, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 2. department of anesthesiology, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2016; accepted: jun 2016; published online: 9 january 2017 abstract: introduction: pain is the most common complaint of patients referring to emergency department (ed). considering the importance of pain management in ed, this study aimed to investigate the efficacy and feasibility of ultrasound-guided nerve blocks in this setting. methods: 46 patients who came to the ed with injured extremities were enrolled in the study and received either femoral, axillary or sciatic nerve block depending on their site of injury (1.5 mg bupivacaine per kg of patient’s weight). patients were asked about their level of pain before and after receiving the nerve block based on numerical rating scale. the difference between pre and post block pain severity was measured. both patients and physicians were asked about their satisfaction with the nerve block in 5 tiered likert scale. results: 46 patients with the mean age of 37.5 ± 12.5 years (8-82 years) received ultrasound-guided nerve block (84.8% male). 6 sciatic, 25 axillary, and 15 femoral nerve blocks were performed. mean pain severity on nrs score at the time of admission was 8.1 ± 1.4, which reduced to 2.04 ± 2.06 after block. 25 (54.3%) patients were highly satisfied (likert scale 5), 15 (32.6%) were satisfied (likert scale 4), 3 (6.5%) were neutral and had no opinion (likert scale 3), 1 (2.1%) was not satisfied (likert scale 2), and 2 (4.3%) were highly unsatisfied (likert scale 1). there was no significant difference among the satisfaction scores within the three block locations (p = 0.8). there was no significant difference in physicians level of satisfaction between the three block locations either (p = 0.9). 1 (2.1%) case of agitation and tachycardia and 1 (2.1%) case of vomiting were observed after the procedure. conclusion: ultrasound-guided nerve block of extremities is a safe and effective method that can be used for pain management in the ed. it results in high levels of satisfaction among both patients and physicians. keywords: nerve block; ultrasonography, interventional; pain management; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: nejati a, teymourian h, behrooz l, mohseni gh. pain management via ultrasound-guided nerve block in emergency department; a case series study. emergency. 2017; 5(1): e12. 1. introduction p ain is the most common complaint of patients presented to the emergency department (ed) (1). in addition, many ed procedures, such as fracture reduction, need local anesthesia to gain patient’s cooperation during the procedure. procedural sedation and analgesia (psa) require airway and hemodynamic monitoring, which may be time-consuming for physicians and the ed staff. psa has rare yet serious side effects such as hypotension, allergic reactions, and respiratory compromise. in this regard, nerve ∗corresponding author: houman teymourian; department of anesthesiology, shohada-e-tajrish hospital, shahrdari street, tajrish square, tehran, iran. email: tel: +98-9121156198. , email: houman72625@yahoo.com. blocks can be used as effective and safe tools for pain management in ed as it does not require airway monitoring or long-term care. hematoma, infection, and pneumothorax are among its complications. however, using the ultrasoundguided method reduces these side effects (2, 3). physicians challenges in finding anatomical landmarks and limitations of special devices such as electric stimulators of nerves are a few of the reasons behind the limited use of this technique in ed. ultrasound-guided nerve blocks were first introduced in anesthesiology in 1978 when la grange et al. used a doppler device for performing a supraclavicular block of the brachial plexus (4). however, it was later in 1994 that ultrasound was used for showing the exact location for injection of the anesthetic in the area around a nerve (5). in the previous studies on patients with extremity injury, the results have shown high this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com houman72625@yahoo.com. a. nejati et al. 2 efficacy of nerve blocks and no serious side effects have been reported (2, 6, 7). in 2005, in a study by liebmann et al., radial, ulnar and median nerve blocks with ultrasound guide were done by emergency physicians. their results showed that all of the procedures (100%) were completed without need for extra anesthetic agent. 92% of the patients indicated that they would want to receive nerve blocks again if pain control was needed. they concluded that specialists, fellows and residents can perform ultrasound-guided nerve blocks, successfully (6). in one controlled trial, nerve block was used for pain control in femoral neck fractures in the ed of rotherham general hospital. patients who received nerve block reported less time to achieve the lowest level of pain (8). beaudoin et al. did a study on femoral nerve block in 2010 and concluded that femoral nerve block with ultrasound guide is effective and useful for pain management in the ed (7). nerve block is a relatively new concept in the ed. considering the importance of pain management in ed and the limited work on ultrasound-guided nerve blocks in iran, this study aimed to investigate the efficacy and feasibility of this technique in the ed. 2. methods 2.1. study design this study was conducted in the ed of an academic hospital by the emergency medicine physician. the study design was approved by the ethics committee of tehran university of medical sciences and all researchers adhered to all principles of helsinki declaration during the study period. after thorough explanation of the procedure, written informed consent was signed by all enrolled patients. 2.2. participants patients who had pain in their upper or lower extremities following trauma and injury, with pain severity higher than or equal to 4, based on numeric rating scale (nrs), were included. finding a neurological defect in physical examination; planning to transfer the patient to the operation room within 12 hours; allergic history to local anesthetics; infection, hematoma or active bleeding at the site of injection; closed fractures (due to the risk of compartment syndrome); unstable vital signs or glasgow coma scale < 15; using narcotic agents in the past 24 hours; pregnancy; moderate to severe head trauma with prolonged vomiting, severe progressive headache, rhinorrhea, otorrhea and bleeding from ear and nose; serious thoracic, abdominal or vertebral injuries; speech difficulties; intoxication with alcohol and drugs; mental retardation; and history of seizure were among the exclusion criteria. 2.3. data gathering patients characteristics (age, sex), medical history (history of narcotic use within the past 24 hours and allergy), and vital signs (heart rate and blood pressure) were taken and recorded at the time of admission. a complete physical examination of the injured extremity was performed and the patient’s pain was measured before (baseline), and one hour after the procedure based on nrs. bupivacaine with maximum dose of 1.5 mg/kg was used for nerve block and distilled water was used to reach the desired volume (50 cc for axillary, 40 cc for femoral and 40 cc for sciatic nerve block). under sterile conditions, using a 20 or 22 gauge lumbar puncture needle, 50 cc syringe and an extension tube, ultrasoundguided nerve block was performed by a trained emergency physician according to the standard guidelines. a linear probe with a frequency of 7.5 mhz was used for ultrasonography of nerve block locations. one hour after the nerve block, patients blood pressure and heart rate were checked again. satisfaction of patient and physician from the procedure was recorded based on 5 tiered likert scale. satisfaction rate ranged from 5 meaning highly satisfied to 1 meaning highly unsatisfied. patients were monitored for two hours and possible complications such as nausea/vomiting, seizure, headache, hypotension and any other complications were recorded. 2.4. statistical analysis all the data were entered into spss 21. first, descriptive characteristics and frequencies were calculated. continuous variables were reported as mean ± standard deviation and categorical ones as frequency and percentage. 3. results 46 patients with the mean age of 37.5 ± 12.5 years (8-82 years) received ultrasound-guided nerve block (84.8% male). 6 sciatic, 25 axillary, and 15 femoral nerve blocks were performed. mean pain severity on nrs score at the time of admission was 8.1 ± 1.4, which reduced to 2.04 ± 2.06 after block. 25 (54.3%) patients were highly satisfied (likert scale 5), 15 (32.6%) were satisfied (likert scale 4), 3 (6.5%) were neutral and had no opinion (likert scale 3), 1 (2.1%) was not satisfied (likert scale 2), and 2 (4.3%) were highly unsatisfied (likert scale 1). there was no significant difference among the satisfaction scores within the three block locations (p = 0.8). there was no significant difference in physicians level of satisfaction between the three block locations either (p = 0.9). mean systolic blood pressure of patients before and after nerve block were 125.3 ± 5.3 and 119.7 ± 4.8 mmhg, respectively (p < 0.001). also, mean pulse rate of patients before and after nerve block were 94.76 ± 4.4 and 87.23 ± 5.6, respectively (p < 0.001). 1 (2.1%) case of agitation and tachycardia and 1 (2.1%) case of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e12 vomiting were observed after the procedure. 4. discussion this prospective case series study concluded that ultrasound-guided nerve block, decreases pain by more than 75% and reduces patients pain from severe (nrs>8) to tolerable (nrs=2) with minimal side effects. both physicians and patients were more than 80% satisfied with pain reduction using this method regardless of the block location. although there was a significant reduction in blood pressure and heart rate after receiving the nerve block, it was not clinically important. there are many similar studies on the efficacy of proximal nerve blocks in pain reduction for patients, especially performing nerve block under ultrasound guide, which leads to more precision and fewer side effects (9-17). the efficacy of the nerve block is enough to even perform serious surgeries on the patients (9, 11, 14). wang et al. concluded in their study that ultrasound-guided nerve block is a better pain reduction method than epidural analgesia (12). a few other studies, in which ultrasound-guided nerve block and psa were compared, stated that performing nerve block takes less time, patient needs shorter monitoring and observation period and there are also fewer side effects compared to sedation (12, 17, 18). various side effects have been reported for nerve blocks, which can be divided to local and systemic. local side effects are the side effects that manifest due to needle at the site of injection. some of these side effects such as arterial puncture, hematoma at the site of injection, infection, phlebitis and thrombosis are common among all types of nerve blocks. some of the other side effects depend on the anatomic site of the nerve block and its technique as well as the experience of the person performing the nerve block. these include side effects such as: pneumothorax/hemothorax (in axillary, infraclavicular, supraclavicular and rarely suprascalene nerve block) and arteriovenous fistula. systemic side effects can happen because of direct injection of anesthetic into the artery or vein which are very rare, and about 0 with ultrasound guide. the incidence of such side effects may increase due to frequent attempts for finding the nerve, injury to the artery or vein, and using the blind method (without ultrasound guide) or with nerve stimulator (16). in our study, one patient got irritable and agitated, and developed tachycardia, which was controlled with minor intervention (2 mg of midazolam was administered and the patient calmed down afterwards). there was one report of nausea and vomiting, which was relieved without any interventions. in one study, nausea due to nerve block was reported to be much lower than nausea after sedation (12). in this study, 40 (87%) patients were satisfied with the results (very satisfied or satisfied) and three patients (6.4% of all the patients) were not satisfied. the strong existing correlation between the level of pain and patient satisfaction seems logical considering the effectiveness of nerve block in reducing their pain. cases of the three dissatisfied patients were investigated. one of them had a deep massive laceration on his shin in addition to femoral fracture which was the reason he got nerve block, this patient did not receive sciatic nerve block at the same time and this was disappointing to the patient since the pain from the laceration was not relieved and so he was unhappy with the procedure. pain of the other two patients was not relieved after the block, which led to their dissatisfaction. in a study, luber et al. reported 92% overall satisfaction among patients undergoing lumbar plexus block (19). in this study, more than 80% of the physicians were satisfied with the results. this can be due to the feasibility of conducting an ultrasound-guided nerve block, patient’s cooperation and the final effects of the procedure. although physicians satisfaction from the three types of nerve blocks were not significantly different, higher levels of satisfaction from axillary nerve block compared to sciatic, could be due to its easier execution or faster identification of the nerve, as for femoral nerve block it could be because of the proximity of this nerve to the artery which leads to an easier nerve mapping and better access. 5. limitations we did not measure the time spent to perform the nerve block under the guidance of ultrasound. patients were monitored for two hours after receiving nerve block and their pain was only measured once after the procedure, it would have been better to evaluate their pain more than only once and during a longer period. considering that we included three types of nerve blocks, the number of our sciatic cases was low and may not have been enough for drawing conclusions. in addition, all of the nerve blocks were conducted by one person which decreases the generalizability. 6. conclusion ultrasound-guided nerve block of extremities is a safe and effective method that can be used for pain management in the ed. it results in high levels of satisfaction among both patients and physicians. 7. appendix 7.1. acknowledgements the contribution of all ed staff of imam khomeini hospital is appreciated. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. nejati et al. 4 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. ducharme j. emergency pain management: a canadian association of emergency physicians (caep) consensus document. the journal of emergency medicine. 1994;12(6):855-66. 2. bhoi s, chandra a, galwankar s. ultrasound-guided nerve blocks in the emergency department. journal of emergencies, trauma, and shock. 2010;3(1):82. 3. stone mb, wang r, price dd. ultrasound-guided supraclavicular brachial plexus nerve block vs procedural sedation for the treatment of upper extremity emergencies. the american journal of emergency medicine. 2008;26(6):706-10. 4. la grange pdp, foster p, pretorius l. application of the doppler ultrasound bloodflow detector in supraclavicular brachial plexus block. british journal of anaesthesia. 1978;50(9):965-7. 5. kapral s, krafft p, eibenberger k, fitzgerald r, gosch m, weinstabl c. ultrasound-guided supraclavicular approach for regional anesthesia of the brachial plexus. anesthesia & analgesia. 1994;78(3):507-13. 6. liebmann o, price d, mills c, gardner r, wang r, wilson s, et al. feasibility of forearm ultrasonography-guided nerve blocks of the radial, ulnar, and median nerves for hand procedures in the emergency department. annals of emergency medicine. 2006;48(5):558-62. 7. beaudoin fl, nagdev a, merchant rc, becker bm. ultrasound-guided femoral nerve blocks in elderly patients with hip fractures. the american journal of emergency medicine. 2010;28(1):76-81. 8. fletcher ak, rigby as, heyes fl. three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency department: a randomized, controlled trial. annals of emergency medicine. 2003;41(2):227-33. 9. herring aa, stone mb, nagdev ad. ultrasound-guided abdominal wall nerve blocks in the ed. the american journal of emergency medicine. 2012;30(5):759-64. 10. haines l, dickman e, ayvazyan s, pearl m, wu s, rosenblum d, et al. ultrasound-guided fascia iliaca compartment block for hip fractures in the emergency department. the journal of emergency medicine. 2012;43(4):692-7. 11. ferraro lhc, tardelli ma, yamashita am, cardone jdb, kishi jm. ultrasound-guided femoral and sciatic nerve blocks in an anticoagulated patient. case reports. brazilian journal of anesthesiology. 2010;60(4):422-8. 12. wang f, liu l-w, hu z, peng y, zhang x-q, li q. ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty: a multicenter randomized controlled study. brazilian journal of anesthesiology (english edition). 2015;65(1):14-20. 13. shteynberg a, riina lh, glickman lt, meringolo jn, simpson rl. ultrasound guided lateral femoral cutaneous nerve (lfcn) block: safe and simple anesthesia for harvesting skin grafts. burns. 2013;39(1):146-9. 14. perov s, patel p, kumar s, mckelvey gm, chidiac e, motlani f. effective low dosage of mepivacaine in ultrasoundguided axillary nerve block: a double-blinded, randomized clinical trial of efficacy in patients undergoing distal upper extremity surgery. journal of clinical anesthesia. 2014;26(3):222-6. 15. newton-brown e, fitzgerald l, mitra b. audit improves emergency department triage, assessment, multi-modal analgesia and nerve block use in the management of pain in older people with neck of femur fracture. australasian emergency nursing journal. 2014;17(4):176-83. 16. koscielniak-nielsen z. ultrasound-guided peripheral nerve blocks: what are the benefits? acta anaesthesiologica scandinavica. 2008;52(6):727-37. 17. blaivas m, adhikari s, lander l. a prospective comparison of procedural sedation and ultrasound-guided interscalene nerve block for shoulder reduction in the emergency department. academic emergency medicine. 2011;18(9):922-7. 18. wathen je, gao d, merritt g, georgopoulos g, battan fk. a randomized controlled trial comparing a fascia iliaca compartment nerve block to a traditional systemic analgesic for femur fractures in a pediatric emergency department. annals of emergency medicine. 2007;50(2):162-71. e1. 19. luber mj, greengrass r, vail tp. patient satisfaction and effectiveness of lumbar plexus and sciatic nerve block for total knee arthroplasty. the journal of arthroplasty. 2001;16(1):17-21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitations conclusion appendix references emergency. 2017; 5 (1): e1 or i g i n a l re s e a rc h effect of positive end-expiratory pressure on central venous pressure in patients under mechanical ventilation majid shojaee1, anita sabzghabaei2, hossein alimohammadi1, hojjat derakhshanfar1, afshinamini1, bahareh esmailzadeh1∗ 1. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: november 2015; accepted: january 2016; published online: 8 january 2017 abstract: introduction: finding the probable governing pattern of peep and cvp changes is an area of interest for incharge physicians and researchers. therefore, the present study was designed with the aim of evaluating the relationship between the mentioned pressures. methods: in this quasi-experimental study, patients under mechanical ventilation were evaluated with the aim of assessing the effect of peep change on cvp. non-trauma patients, over 18 years of age, who were under mechanical ventilation and had stable hemodynamics, with inserted cv line were entered. after gathering demographic data, patients underwent 0, 5, and 10 cmh2o peeps and the respective cvps of the mentioned points were recorded. the relationship of cvp and peep in different cut points were measured using spss 21.0 statistical software. results: 60 patients with the mean age of 73.95 ± 11.58 years were evaluated (68.3% male). the most frequent cause of icu admission was sepsis with 45.0%. 5 cmh2o increase in peep led to 2.47 ± 1.53 mean difference in cvp level. if the peep baseline is 0 at the time of 5 cmh2o increase, it leads to a higher raise in cvp compared to when the baseline is 5 cmh2o (2.47 ± 1.53 vs. 1.57 ± 1.07; p = 0.039). the relationship between cvp and 5 cmh2o (p = 0.279), and 10 cmh2o (p = 0.292) peep changes were not dependent on the baseline level of cvp. conclusion: the findings of this study revealed the direct relationship between peep and cvp. approximately, a 5 cmh2o increase in peep will be associated with about 2.5 cmh2o raise in cvp. when applying a 5 cmh2o peep increase, if the baseline peep is 0, it leads to a significantly higher raise in cvp compared to when it is 5 cmh2o (2.5 vs. 1.6). it seems that sex, history of cardiac failure, baseline cvp level, and hypertension do not have a significant effect in this regard. keywords: positive-pressure respiration; central venous pressure; ventilators, mechanical; catheterization, central venous; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: shojaee m, sabzghabaei a, alimohammadi h, derakhshanfar h, amini a, esmailzadeh b. effect of positive end-expiratory pressure on central venous pressure in patients under mechanical ventilation. emergency.2017;5(1): e1. 1. introduction a vast number of patients visiting emergency department (ed) need intubation due to their level of consciousness and clinical status, and are kept under mechanical ventilation. these patients may also require central venous (cv ) line insertion for different reasons such as inability to access peripheral vein, blood transfusion, or administration of vasoactive agents (1). central venous pressure (cvp) is a good indicator of circulatory volume ∗corresponding author: bahareh esmailzadeh; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel:00989124034956 , email: bahareesmailzadeh@gmail.com. and cardiac function, which may be influenced by various factors such as function of right atrium and ventricle, venous tone, and intra-thoracic pressure(1). considering the afore-mentioned utilities, cvp monitoring is routinely used in operating rooms, intensive care units (icu), and eds. the normal range of cvp is 8-12cmh2o, which increases to 12-16 cmh2o in patients under mechanical ventilation (1, 2). factors such as incorrect adjustment of the ruler’s zero point, patient’s poor condition, inappropriate placement of the catheter, and using vasopressor may interfere with accurate cvp measurement (1). positive end-expiratory pressure (peep) in patients under mechanical ventilation can affect cvp via increasing intra-thoracic pressure. various reports exist on the direct relationship between the 2 pressures this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com bahareesmailzadeh@gmail.com m. shojaee et al. 2 (3). yet, there is no accurate formula or solution based on peep level for adjusting cvp in patients under mechanical ventilation. yang et al. showed that a 0.38 cmh2o increase in peep leads to 1 cmh2o raise in cvp (4). a study on 70 cardiac surgery patients in 2007 showed that mean cvp of the patients in 0, 5, and 10 cmh2o peeps are 11, 12, and 14 cmh2o, respectively (5). finding theprobable governing pattern of peep and cvp changes is an area of interest for in-charge physicians and researchers. therefore, the present study was designed with the aim of evaluating the relationship between the mentioned pressures. 2. methods 2.1. study design and setting in this quasi-experimental study, patients under mechanical ventilation who were hospitalized in the icu of imam hossein hospital, tehran, iran, were evaluated with the aim of assessing the effect of peep change on cvp. the study was approved by the ethics committee of shahid beheshti university of medical sciences in their 147t h meeting in february 2013. since the patients were not able to give written informed consent, it was obtained from their relatives. the researchers were committed to protecting patient rights and confidentiality in line with the principles of helsinki declaration. 2.2. participants non-trauma patients, over 18 years of age, who were under mechanical ventilation and had stable hemodynamics, with inserted cv line were entered. to eliminate other confounding factors of cvp, all the patients were deeply sedated and under the same ventilator settings including tidal volume = 8 10 cc/kg, pressure support = 12 14 cmh2o, fio2 = 40 70%, flow = 10 12 l/minute, and peep = 0, 5, and 10 cmh2o. intake volume per hour was in a similar range for all the patients and the patient was excluded if more than 200 cc/hour intravenous isotonic fluid was needed to maintain hemodynamic stability. patients with auto peep (more than 2 cmh2o difference between the peep reported by the device and the one set for the patient), what ever the reason, were excluded. in addition, patients who were in need of > 10 cmh2o peep, for example patients withacute respiratory distress syndrome (ards), were not evaluated. the ventilator devices used for the patients were all the same model and from the same manufacturer. 2.3. data gathering after gathering demographic data of the patients using a checklist designed for this study, patients underwent 0, 5, and 10 cmh2o peeps and the respective cvps of the mentioned points were measured and recorded. the time considered for adjustment of cvp with any of the peep cut-off points was considered 10 minutes (3). to accurately measure cvp, all measurements were carried out by the same person, in supine position, and by setting the zero point of the cv line ruler at sternal notch level. to minimize errors, measurement for every patient was done twice for each peep cut point with 30minutes intervals and their mean was considered the reference cvp measure. in cases of wide difference between the 2 measurements, a third measurement was done and the mean of the 2 closest measures was considered to be the reference. if aparticipant showed hypoxia and hemodynamic instability at any time of the study, he/she was eliminated from the study and necessary interventions were carried out to stabilize his/her status. all the calculated measures for cvp in each peep cut point was recorded in the prepared checklist and used for analysis. 2.4. statistical analyses the sample size needed for the present study was calculated based on a pilot study and using a standard deviation to estimate the minimum sample size needed.therefore, by considering zα = 0.5%, p = 95%, minimum clinically considerable cvp difference of 1 cmh2o (d = 1), and the difference between the standard deviation of cvp in peep 10 and 0 of 1.4 (sd i f f = 1.4), the sample size needed was calculated to be 26 cases. patient data were analyzed using spss 21.0. quantitative data were reported as mean and standard deviation and qualitative ones as frequency and percentage. to compare cvp before and after applying various peeps, paired ttest or non-parametric wilcoxon test were used. in all tests, p < 0.05 was considered as significance level. 3. results 60 patients with the mean age of 73.95 ± 11.58 years (46 93) were evaluated (68.3% male). the most frequent cause of icu admission was sepsis with 45.0%. table 1 shows the baseline characteristics of the studied patients. table 2 shows the relationship between various peep measures and cvp. 5 cmh2o increase in peep led to 2.47 ± 1.53 mean difference in cvp level. if the peep baseline is 0 at the time of 5 cmh2o increase, it leads to a higher raise in cvp compared to when the baseline is 5 cmh2o (2.47 ± 1.53 vs. 1.57 ± 1.07; p = 0.039). adjusting the analyses done in table 2 based on sex, presence of cardiac failure and history of hypertension did not show any significant differences in the mentioned relations (table3). evaluation of the relationship between changes in peep and cvp measures based on different levels of cvp are summarized in table 4. the relationship between cvp and 5 cmh2o (p = 0.279), and 10 cmh2o (p = 0.292) peep changes were not dependent on the baseline level of cvp. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e1 table 1: baseline characteristics of the studied population studied variables mean ± sd (range) systolic bp (mmhg) 125.533 ± 20.55 (100 170) diastolic bp (mmhg) 74.583 ± 11.21 (60 100) heart rate/minute 90.96 ± 15.34 (60 120) age (year) frequency (%) 18 39.9 0 (0) 40 59.9 7 (11.7) 60 79.9 29 (48.3) ≥ 80 24 (40) hx of cardiac failure yes 12 (20) no 48 (80) hx of hypertension yes 43 (71.7) no 17 (28.3) cause of admission pneumosepsis 14 (23.3) urosepsis 13 (21.7) cerebrovascular accident 8 (13.3) metastatic cancer 4 (6.7) other 21 (35) bp: blood pressure; sd: standard deviation. table 2: correlation between different positive end-expiratory pressures (peep) and central venous pressures (cvp) in studied patients peep (cmh2 o) cvp (mean ± sd) (cmh2 o) p value paired 1 0 7.81 ± 5.99 < 0.001 5 10.29 ± 5.67 paired 2 0 7.81 ± 5.99 < 0.001 10 11.86 ± 5.72 paired 3 ∆ 0-5 2.47 ± 1.53 < 0.001 ∆ 0-10 4.05 ± 2.09 paired 4 ∆ 0-5 2.47 ± 1.53 < 0.003 ∆ 5-10 1.57 ± 1.07 sd: standard deviation. 4. discussion the findings of this study showed that an increase in peep has a direct relationship with cvp increase. approximately, a 5 cmh2o increase in peep will be associated with about 2.5 cmh2o raise in cvp. when applying a 5 cmh2o peep increase, if the baseline peep is 0, it leads to a significantly higher raise in cvp compared to when it is 5 cmh2o (2.5 vs. 1.6). it seems that sex, history of cardiac failure, hypertension, and baseline cvp do not significantly affect cvp increase rate. in a study by yang et al. 1 cmh2o increase in peep, led to 0.38 cmh2o increase in cvp, which is approximately in line with the present study (4). a study on the effect of peep in patients under mechanical ventilation showed a significant direct relation ship between 0, 5, and 10 cmh2o peeps with cvp. the cvp increase was related to mean peep during mechanical ventilation when peep was set 10 or less, in a study by cao et al. which is in line with this study (6). evaluating the effect of peep on cvp and stroke volume in 20 patients with cardiac diseases, revealed that peep significantly affects cvp, while no significant relationship was detected between heart rate and mean arterial pressure (7). in the present study, 5 cmh2o increase in peep, led to 1.5 2.5 cmh2o increase in cvp. currently, cvp is used as a guide for fluid therapy efficiency and monitoring the effects of intake volume on cardiovascular system. many current treatment protocols, especially regarding septic shock patient management, define the aim of the treatment as achieving a cvp of 8 -12 cmh2o in patients without ventilator and 12 -16 cmh2o in those under mechanical ventilation. however, the study by cao et al. showed that in patients under ventilator and peep, cvp alone is not a good reference for estimation of circulatory volume and required fluid volume for resuscitation (8). considering the existing controversies in this regard, it seems that we should seek more accurate scales for determining the efficacy of fluid therapy in patients under mechanical ventilation. until then, the best way might be using modified cvp based on peep rate. 5. limitations since the present study was carried out on patients hospitalized in the icu, some limitations should be noted: first, patients with a variety of underlying illnesses were included, which can affect the results. second, the patients have been in different phases of hospitalization, therefore the rates and efficiencies of treatments received (fluid, vasoactive drugs) were different among them. in addition, cvp measurement using a ruler has some limitations in its nature, such as adjusting the zero point. naturally, there are some limitations for applying long-term peepsin these patients, which can affect the conclusion. it is suggested to eliminate the aforementioned limitations to accurately evaluate the effect of peep on cvp in future studies. 6. conclusion the findings of this study revealed the direct relationship between peep and cvp. approximately, a 5 cmh2o increase in peep will be associated with about 2.5 cmh2o raise in cvp. when applying a 5 cmh2o peep increase, if the baseline peep is 0, it leads to a significantly higher raise in cvp compared to when it is 5 cmh2o (2.5 vs. 1.6). it seems that sex, history of cardiac failure, baseline cvp level, and hypertensiondo not have a significant effectin this regard. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. shojaee et al. 4 table 3: correlation between different positive end-expiratory pressures (peep) and sex, and history of heart failure and hypertension sex∗ heart failure∗∗ hypertension∗∗∗ peep (cmh2 o) mean ± sd p value mean ± sd p value mean ± sd p value peep 0 0 7.23±5.00 0.27 7.22±5.79 0.13 8.02±1.14 0.86 1 9.07±7.73 10.16±6.46 7.73±4.81 peep 5 0 9.74±4.73 0.27 9.94±5.48 0.35 10.61±7.92 0.78 1 11.47±7.32 11.66±6.47 10.16±4.61 peep 10 0 11.54±4.97 0.53 11.60±5.52 0.48 11.91±7.72 0.97 1 12.55±7.20 12.91±6.64 11.84±4.83 ∆0-5 0 2.51±1.66 0.78 2.71±1.55 0.01 2.58±1.20 0.72 1 2.39±1.23 1.50±0.97 2.43±1.65 ∆5-10 0 1.80±1.15 0.01 1.65±1.06 0.24 1.29±0.83 0.20 1 1.07± 0.65 1.25±1.07 1.68±1.14 ∆0-10 0 4.31±2.24 0.14 4.37±2.12 0.01 3.88±1.63 0.70 1 3.47±1.61 2.75±1.37 4.11±2.26 sex∗(0= male, 1= female), heart failure ∗∗(0= no, 1= yes), hypertension∗∗∗ (0= no, 1= yes). table 4: of correlation between positive end-expiratory pressures (peep) and central venous pressure (cvp) in different baseline cvp levels peep (cmh2 o) ∆ cvp (cmh2 o) p value ∆ peep 5 cvp < 8 2.7±1.7 0.279 cvp = 8-12 2.4±1.2 cvp > 12 1.8±1.2 ∆ peep 10 cvp < 8 4.3±2.3 0.279 cvp = 8-12 4.1±1.3 cvp > 12 3.1±1.9 7. appendix 7.1. acknowledgements the authors appreciate the insightful cooperation of emergency department staff. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding none. 7.4. conflict of interest none. references 1. marino pl, sutin km. the icu book: williams , wilkins baltimore:; 1998. 2. wai a. roberts and hedges: clinical procedures in emergency medicine. lww; 2010. 3. roberts jr, hedges jr. clinical procedures in emergency medicine: elsevier health sciences; 2009. 4. yang z, zhou j, sun b, qian z, zhao h, liu w. [the influence of positive end-expiratory pressure on central venous pressure in patients with severe craniocerebral injury]. zhongguo wei zhong bing ji jiu yi xue= chinese critthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e1 ical care medicine= zhongguo weizhongbing jijiuyixue. 2012;24(5):283-5. 5. marx j, walls r, hockberger r. rosen’s emergency medicine-concepts and clinical practice: elsevier health sciences; 2013. 6. cao f, liu x, chen r, wang x. [effect of positive endexpiratory pressure on central venous pressure and common iliac venous pressure in mechanically ventilated patients]. zhongguo wei zhong bing ji jiu yi xue= chinese critical care medicine= zhongguo weizhongbing jijiuyixue. 2008;20(6):341-4. 7. geerts b, aarts l, groeneveld a, jansen j. predicting cardiac output responses to passive leg raising by a peep-induced increase in central venous pressure, in cardiac surgery patients. british journal of anaesthesia. 2011;107(2):150-6. 8. cao f, chen r, liu x, he r. [effect of positive endexpiratory pressure on the pressure gradient of venous return in hypovolemic patients under mechanical ventilation]. zhongguo wei zhong bing ji jiu yi xue= chinese critical care medicine= zhongguo weizhongbing jijiuyixue. 2009;21(10):583-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitations conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e9 or i g i n a l re s e a rc h clinical predictors of testicular torsion in patients with acute scrotum; a cross-sectional study mohammad sazgar1, seyed hossein montazer2, seyed mohammad hosseininejad3, fatemeh jahanian1, behkam rezaimehr4, mohammad behbohaninia5, hamed aminiahidashti1∗ 1. department of emergency medicine, mazandaran university of medical sciences, sari, iran. 2. orthopedic research center, mazandaran university of medical sciences, sari, iran. 3. diabetes research center, mazandaran university of medical sciences, sari, iran. 4. department of urology, mazandaran university of medical sciences, sari, iran. 5. student research committee, faculty of medicine, mazandaran university of medical sciences, sari, iran. received: december 2021; accepted: december 2021; published online: 11 january 2022 abstract: introduction: testicular torsion is an important and critical issue in patients with acute scrotum referring to emergency department (ed). early detection is very important to save the testicles. this study aimed to determine the diagnostic accuracy of clinical variables in predicting the presence of testicular torsion. methods: this prospective cross-sectional study was done using the information of patients hospitalized from september 2015 to september 2020, with complaint of acute scrotum (icd 10 code: n50.8), referring to ed for evaluation of the clinical predictors of testicular torsions, which were confirmed by surgery. results: 81 patients with the mean age of 20.07 ± 9.64 (345) years were studied. after surgical exploration, 70 patients (86.4%) had testicular torsion. patients with torsion had lower age (p < 0.0001), lower time from symptom to ed visit (p < 0.0001), sudden onset pain (p = 0.003), left side pain (p < 0.0001), and lower white blood cell (wbc) count (p = 0.001). the frequency of dysuria (p = 0.032), diarrhea/vomiting (p = 0.005), and fever (p = 0.002) was significantly lower in patients with torsion. the cremasteric reflex was absent in 57 (81.4%) cases who suffered from testicular torsion (p = 0.001). based on the results of binary logistic regression analysis, age (b = -0.175, se = 0.45; p < 0.0001) was the sole independent predictor of testicular torsion. the highest area under the receiver operating characteristics (roc) curve in predicting the presence of torsion belonged to lower age [91.0 (95%ci: 83.2 – 98.7)], pain in left testis [0.931 (95%ci: 0.828-0.987)], and lower wbc count [0.805 (95%ci: 0.684-0.926)], respectively. conclusion: it seems that clinical variables are not accurate enough to be considered as the sole predictor of testicular torsion and they should be used with caution and in combination with other available screening tools like doppler ultrasonography in this regard. keywords: scrotum; acute pain; spermatic cord torsion; early diagnosis; emergency service, hospital cite this article as: sazgar m, montazer s h, hosseininejad s m, jahanian f, rezaimehr b, behbohaninia m, aminiahidashti h. clinical predictors of testicular torsion in patients with acute scrotum; a cross-sectional study. arch acad emerg med. 2022; 10(1): e9. https://doi.org/10.22037/aaem.v10i1.1484. 1. introduction acute scrotum or testicular pain is one of the most important problems in the emergency department (ed). acute scrotum is defined as a sudden onset scrotum pain with or with∗corresponding author: hamed aminiahidashti; department of emergency medicine, emam khomeini hospital, amirmazandarani bolivar, sari, mazandaran province, iran. tell: +981133361700, orcid: http://orcid.org/00000002-2115-1903. out edema and tenderness, which is a true surgical emergency due to the possibility of testicular torsion (1, 2). there are a wide range of differential diagnoses for acute scrotum, and early detection of testicular torsion is essential (3). epididymo-orchitis, torsion of the appendix testis, and inguinal herniation are some of the causes of presenting with acute scrotum symptoms (4). in some medical centers, all patients with acute scrotum are surgically explored to rule out testicular torsion (5, 6). there is clinical guidance in this regard, but it is not accepted worldwide (7). color doppler ultrasonography of the testis is used as a fast method with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sazgar et al. 2 high sensitivity and specificity in the diagnosis of testicular torsion (8, 9). however, false-negative results are possible in the early stage, incomplete torsion, and intermittent torsion; therefore, clinical signs should be considered (10). nevertheless, differentiating testicular torsion from other causes of the acute scrotum in the emergency department is crucial (11) and diagnostic exploration should be performed if the diagnosis still remains in doubt (12). based on the abovementioned points, this study aimed to determine the diagnostic accuracy of clinical variables in predicting the presence of testicular torsion. 2. methods 2.1. study design and setting this prospective cross-sectional study was done using the information of patients hospitalized from september 2015 to september 2020, with complaint of acute scrotum (icd 10 code: n50.8), referring to the ed of imam khomeini hospital, sari, iran, affiliated to mazandaran university of medical sciences. the association between clinical characteristics and presence of testicular torsion (confirmed via surgery by urologist) was studied. this study was approved by the ethics committee of mazandaran university of medical sciences (ir.mazums.rec.94-1313). the research team adhered to the ethical principles of the helsinki convention regarding clinical studies. 2.2. participants all patients referring to the ed with the complaint of acute scrotum, which was initially diagnosed as testicular torsion based on international classification of disease, version 10 (icd10) code: n44) and underwent surgical exploration were included. patients with incomplete information, those diagnosed with conditions other than testicular torsion, and also cases with underlying testicular diseases, such as a testicular tumor, cryptorchidism, and history of surgery were excluded from the study. informed consent was obtained from all eligible patients or their legal representatives. the executor has adhered to the all the principles of the helsinki declaration. 2.3. data gathering data regarding baseline characteristics, clinical examinations, history taking, and operating room reports of all patients was extracted from patients’ profiles and collected in a data collection form. variables such as age, type of pain, time from beginning of pain to ed presentation, dysuria, hematuria, nausea and vomiting, side of pain, fever (t ≥ 38 ° c), cremasteric reflex, tenderness, erythema, and swelling were recorded for all cases. the data were collected by a trained emergency medicine resident under the direct supervision of an emergency medicine specialist. 2.4. statistical analysis considering sensitivity = 0.95 and specificity = 0.8 of redness and swelling of the scrotum and testicular pain (2, 13), 95% confidence interval, the maximum clinically acceptable width = 0.1, and prevalence = 0.25, the required sample size for this study was calculated to be 81 cases. data were analyzed using spss version 21.0 (spss inc, chicago, il, usa). quantitative variables were expressed using mean ± standard deviation or frequency (%). the association between variables and presence of testicular torsion was studied using chi-square or student t test. binary logistic regression analysis was done on variables with significant association to determine the independent predictors of torsion. area under the receiver operating characteristics (roc) curve of each variable in predicting the presence of testicular torsion was calculated and reported with 95% confidence interval. p < 0.05 was considered as an acceptable cut-off for statistical significance. 3. results 3.1. baseline characteristics of studied patients out of the 358 patients referring to the ed with acute scrotum, 81 patients with the mean age of 20.07 ± 9.64 (range: 345) years were suspected to have testicular torsion and were eligible for inclusion (figure 1). the location of pain was the left testis in 67 (82.7%) cases, the right testis in 12 (14.8%), and on both sides in 2 (2.5%) patients. testicular pain was sudden onset in 64 (79.01%) and gradual in 17 (20.98%) cases. dysuria, vomiting, and fever was detected in 17 (20.98%), 35 (43.20%), and 21 (25.92%) cases, respectively. the mean time from the onset of symptoms to ed visit was 6.41 ± 11.01 (range: 1-72) hours. in clinical examinations, 20 (24.69%) patients had cremasteric reflex, 62 (76.54%) erythema, 68 (83.95%) testicular swelling, and 73 (90.12%) patients had testicular tenderness. mean wbc count was 10700 ± 4400 cells/cubic millimeter. 20 (24.69%) patients underwent orchidectomy. 3.2. screening characteristics of clinical findings after surgical exploration, 70 patients (86.4%) had testicular torsion. table 1 compares the baseline characteristics as well as signs and symptoms between cases with and without testicular torsion. patients with testicular torsion had lower age (p < 0.0001), lower time from symptom to ed visit (p < 0.0001), sudden onset pain (p = 0.003), left side pain (p< 0.0001), and lower wbc count (p = 0.001). the frequency of dysuria (p = 0.032), diarrhea/vomiting (p = 0.005), and fever (p = 0.002) was significantly lower in patients with torsion. the cremasteric reflex was absent in 57 (81.4%) cases who suffered from testicular torsion (p = 0.001). based on the rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e9 figure 1: the flow chart of patients’ enrollment to the study. sults of binary logistic regression analysis, age (b = -0.175, se = 0.45; p < 0.0001) was the sole independent factor in prediction of testicular torsion. figure 2 and table 2 show the area under the roc curve of studied variables in predicting testicular torsion. accordingly, the highest area under the roc curve value in this regard belonged to lower age [91.0 (95%ci: 83.2 – 98.7)], pain on the left side [0.931 (95%ci: 0.828-0.987)], and lower wbc count [0.805 (95%ci: 0.684-0.926)], respectively. 4. discussion based on the findings of present study, patients with testicular torsion frequently presented with sudden onset pain in left testicle. the frequency of dysuria, diarrhea/vomiting, and fever, as well as wbc count was significantly lower in these cases. age was the sole independent predictive factor of testicular torsion in this series. the maximum accuracy of studied variables in predicting torsion belonged to lower age, left side pain, and lower wbc count. numerous studies have shown that pain, tenderness, and positive color doppler ultrasound had the highest sensitivity in diagnosis of testicular torsion. it has been shown that some clinical variables such as testicular swelling and stiffness, the lack of cremasteric reflex, and moving up of the testicle had had a combined negative predictive value of 100% (specificity 81%, sensitivity 76%) in predicting testicular torsion (8). age and involvement of the left testicle were independent factors in diagnosis of testicular torsion in fabian et al. study (9), but in this study, age was the sole independent predictor of torsion. it has been shown that irreversible damage to the testis octhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sazgar et al. 4 figure 2: area under the receiver operating characteristics (roc) curve of different signs and symptoms in predicting the presence of testicular torsion (the values with 95% confidence interval are presented in table 2). table 1: comparison of baseline characteristics and clinical findings between cases with and without testicular torsion variables testicular torsion p present (n = 70) absent (n = 11) age (year) 17.92 ± 7.85 33.72 ± 8.94 <0.0001 time to ed visit (hour) 4.35 ± 4.72 19.45 ± 26.39 <0.0001 wbc (cells/mm3) 10039.28 ± 4278.19 14709.09 ± 3439.89 0.001 type of pain sudden 59 (84.3) 5 (45.5) 0.003 gradual 11 (15.7) 6 (54.5) signs and symptoms dysuria 12 (17.1) 5 (45.5) 0.032 diarrhea/vomiting 26 (37.1) 9 (81.8) 0.005 fever 14 (20.0) 7 (63.6) 0.002 hematuria 1 (1.4) 0 (0.0) 0.690 erythema 54 (77.1) 8 (72.7) 0.748 tenderness 64 (91.4) 9 (81.8) 0.321 edema 54 (84.3) 8 (81.8) 0.748 side of pain left 66 (94.3) 1 (9.1) <0.0001 right 4 (5.7) 8 (72.7) both 0 (0.0) 2 (18.2) cremasteric reflex yes 13 (18.6) 7 (63.6) 0.001 no 57 (81.4) 4 (36.4) ed: emergency department; wbc: white blood cell count. curs less frequently in patients with torsion referring to the ed within the first 6 hours of symptom onset and complete infarctions would occur in 90% of cases that present to ed after 24 hours (13). in this study, lower time to ed visit was significantly associated with the presence of testicular torsion. neutrophil to lymphocyte ratio (nlr) was found to have a sensitivity of 84% and specificity of 92% in predicting testicular torsion (10). although an increase in white blood cell count has been shown to be an inflammatory marker in patients with testicular torsion (5), it cannot be used as a marker for differentiating various causes of acute scrotum syndrome (14). also, in this study, patients with testicular torsion had a significantly lower wbc count. it could be concluded that relying on clinical variables as the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e9 table 2: area under the receiver operating characteristics (roc) curve of different signs and symptoms in predicting the presence of testicular torsion test result variable(s) area 95% ci se p-value lower upper age 0.910 0.832 0.987 0.040 <0.0001 side of pain 0.931 0.828 1.000 0.053 < 0.0001 white blood cell 0.805 0.684 0.926 0.062 0.001 cremasteric reflex 0.725 0.549 0.902 0.090 0.017 diarrhea/vomiting 0.723 0.571 0.875 0.078 0.018 fever 0.718 0.542 0.895 0.090 0.021 time to ed presentation 0.715 0.524 0.906 0.098 0.023 type of pain 0.694 0.508 0.880 0.095 0.039 dysuria 0.642 0.450 0.833 0.098 0.133 tenderness 0.548 0.355 0.741 0.098 0.610 erythema 0.522 0.335 0.709 0.096 0.815 hematuria 0.493 0.310 0.676 0.093 0.940 edema 0.488 0.301 0.674 0.095 0.896 ci: confidence interval; se: standard error; ed: emergency department. sole indicator of torsion and need for exploration surgery is not acceptable and decision in this regard should be made with caution and in combination with other findings. 5. limitations the limitations of the study were the high number of patients who did not consent to surgery after being a candidate for surgical exploration and those who were discharged from the emergency room against medical advice. also, since the studied center did not have a pediatric ward, most of the patients were adults. 6. conclusion it seems that, clinical variables are not accurate enough to be considered as the sole predictor of testicular torsion and they should be used with caution and in combination with other available screening tools like doppler ultrasonography in this regard. 7. declarations 7.1. acknowledgments the authors’ thanks emergency department staff for their assistance in conducting the study. 7.2. authors’ contributions ha, smm, br contributed to the project development and study design. mb and ha contributed data collection and interpretation of the data. ha, ms, fj contributed to data analysis. ha, ms, smh developed the manuscript. ha, ms, smh, br critically edited and revised the manuscript. all authors read and approved the final manuscript. 7.3. funding and supports this study was extracted from a thesis project, which was financially supported by a grant (no: 1313) from mazandaran university of medical sciences. 7.4. conflict of interest there are no conflicts of interest. references 1. corbett hj, simpson et. management of the acute scrotum in children. anz journal of surgery. 2002;72(3):2268. 2. boettcher m, bergholz r, krebs tf, wenke k, aronson dc. clinical predictors of testicular torsion in children. urology. 2012;79(3):670-4. 3. gatti jm, patrick murphy j. current management of the acute scrotum. seminars in pediatric surgery. 2007;16(1):58-63. 4. burgher sw. acute scrotal pain. emergency medicine clinics of north america. 1998;16(4):781-809, vi. 5. yang c, jr., song b, liu x, wei gh, lin t, he dw. acute scrotum in children: an 18-year retrospective study. pediatric emergency care. 2011;27(4):270-4. 6. murphy fl, fletcher l, pease p. early scrotal exploration in all cases is the investigation and intervention of choice in the acute paediatric scrotum. pediatric surgery international. 2006;22(5):413-6. 7. tekgül s, riedmiller h, gerharz e, hoebeke p, kocvara r, nijman r, et al. guidelines on paediatric urology. european society for pediatric urology. 2015 mar: 20-1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. sazgar et al. 6 8. barbosa ja, tiseo bc, barayan ga, rosman bm, torricelli fc, passerotti cc, et al. development and initial validation of a scoring system to diagnose testicular torsion in children. the journal of urology. 2013;189(5):1859-64. 9. fabiani a, calabrese m, filosa a, fioretti f, maurelli v, scandola m, et al. explorative surgery for acute scrotal pain: the importance of patient age, side affected, time to surgery and surgeon. archivio italiano di urologia, andrologia. 2016;88(3):189-94. 10. gunes m, umul m, altok m, akyuz m, isoglu cs, uruc f, et al. predictive role of hematologic parameters in testicular torsion. korean journal of urology. 2015;56(4):324-9. 11. sazgar m, behbohaninia m, assadi t, rezaimehr b, mousavi j, aminiahidashti h. causes and symptoms of acute scrotal pain in patients presenting to emergency departments in mazandaran, iran 2011-2016. journal of mazandaran university of medical sciences. 2020; 30(188):132-7. 12. sieger n, di quilio f, stolzenburg ju. what is beyond testicular torsion and epididymitis? rare differential diagnoses of acute scrotal pain in adults: a systematic review. annals of medicine and surgery. 2020;55:265-74. 13. waldert m, klatte t, schmidbauer j, remzi m, lackner j, marberger m. color doppler sonography reliably identifies testicular torsion in boys. urology. 2010;75(5):1170-4. 14. yucel c, ozlem ilbey y. predictive value of hematological parameters in testicular torsion: retrospective investigation of data from a high-volume tertiary care center. the journal of international medical research. 2019;47(2):730-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e39 or i g i n a l re s e a rc h validation of songklanagarind pediatric triage model in the emergency department; a cross-sectional study siriwimon tantarattanapong1∗, nut chonwanich1, wannipha senuphai2 1. department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla, thailand. 2. nursing department, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla, thailand. received: march 2021; accepted: april 2021; published online: 20 may 2021 abstract: introduction: an effective triage needs to consider many factors, such as good triage protocol, experienced triage nurses, and patient factors. this study aimed to evaluate the validity of songklanagarind pediatric triage (spt) for triage of pediatric patients in the emergency department (ed) and identify the factors associated with triage appropriateness. methods: this study was done in two phases. in the first phase, a team of emergency physicians, a pediatric emergency physician, and a pediatric critical care physician developed spt model by considering and combining emergency severity index (esi), pediatric assessment triangle (pat), pediatric canadian triage and acuity scale (paedctas), and pediatric septic shock early warning signs protocol of the hospital as the core concept. in the second phase, a prospective observational study was conducted in the ed of songklanagarind hospital, which is a tertiary university hospital in southern thailand, from september to october 2019 to evaluate the accuracy of the developed triage model. results: a total of 520 pediatric patients met the inclusion criteria. the pediatric triage model had sensitivity and specificity values of 98.28% and 26.24%, respectively, and positive and negative predictive values of 27.67% and 98.15%, respectively, in prediction of death, hospitalization, and resource utilization. the rates of appropriate triage, over-triage, and under-triage were 68.8%, 28.5%, and 2.7%, respectively. significant factors associated with appropriateness of triage were underlying disease of the respiratory system (or = 4.16, 95%ci: 1.75–9.23), fever (or = 0.60, 95%ci: 0.41–0.88), dyspnea (or: 6.38, 95%ci: 2.51–16.22), diarrhea (or = 0.26, 95%ci: 0.09–0.73), oxygen saturation <95% (or = 3.18, 95%ci: 1.09–9.27), accessory muscle use during breathing (or = 3.67, 95%ci: 1.09–12.41), and wheezing or rhonchi (or = 6.96, 95%ci: 3.14–15.43). conclusion: spt showed good correlation of hospital admission rates and resource utilization with pediatric triage level of urgency. however, further efforts are needed to decrease the rates of overand under-triage. keywords: triage; pediatrics; reproducibility of results; emergency service, hospitale cite this article as: tantarattanapong s, chonwanich n, senuphai w. validation of songklanagarind pediatric triage model in the emergency department; a cross-sectional study. arch acad emerg med. 2021; 9(1): e39. https://doi.org/10.22037/aaem.v9i1.1237. 1. introduction the volume of patients in the emergency department (ed) has recently increased, which has resulted in an imbalance between needs and resources (1). a qualified ed must have a standard 5-level triage system to prioritize patients according to severity and need for emergency management in the setting of limited resources (2). patients with more urgent ∗corresponding author: siriwimon tantarattanapong; department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla 90110, thailand. phone: (66)74451705, fax: (66)74-451704, email: tsiriwimon.er@gmail.com, orcid: https://orcid.org/0000-0002-4792-373x. conditions need shorter waiting times to see the doctor. the safety of patients is the major issue. the factors that need to be considered for an effective triage are: a good triage protocol, experienced triage nurses, and patient factors (3). special populations, especially pediatric patients, are challenging for triage. special considerations, including age-specific vital signs and limited development of communication skills, influence the assessment of pediatric patients in the ed (3-5). previous research that evaluated the validity of triage systems relied on two methods: 1) a comparison of the triage system with a reference standard developed by experts and 2) an association of the level of urgency and hospital admission or resource utilization (6). under-triage increases the waiting time and increases morbidity and mortality. according to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and et al. 2 hinson (2018), under-triage in moderate acuity had a critical outcome of 8.5%. conversely, over-triage limits the time and resources for patients most in need (7). at the ed of songklanagarind hospital, which is a tertiary university hospital, the standard 5-level triage protocol was adapted from emergency severity index (esi) version 4.0. the results from a previous study at the ed showed an unexpected correlation between the admission rate and esi level. the admission rates of esi levels 1 to 5 were 57.1%, 21%, 42.2%, 1.4%, and 3.6%, respectively (8). based on the results of the previous study, the songklanagarind pediatric triage (spt) was developed from the core concept of esi version 4.0 and the initial assessment used by the pediatric assessment triangle (pat) (9). the pediatric canadian triage and acuity scale (paedctas) was used adjusted standard vital signs for each age group (10). in addition, the pediatric septic shock early warning sign protocol was used to develop spt. the aim of this study was to evaluate the validity of spt for triage of pediatric patients in the ed and identify the factors associated with triage appropriateness. 2. methods 2.1. study design and setting this study was done in two phases. in the first phase (development phase) a team of emergency physicians, pediatric emergency physician, and the pediatric critical care physician developed the songklanagarind pediatric triage (spt) model by considering and combining esi, pat, paedctas, and pediatric septic shock early warning signs protocol of the hospital as the core concept. in the second phase (validation phase) a prospective observational study was conducted in the ed of songklanagarind hospital, which is a tertiary university hospital in southern thailand, from september to october 2019 to evaluate the accuracy of the developed triage model. ethics approval was obtained from the institutional ethics committee board of the faculty of medicine at prince of songkla university (ethics code: rec.62-153-20-4.) 2.2. development phase the ed of songklanagarind hospital uses the 5-level triage adapted from esi version 4.0. since the triage nurses were familiar with esi, it was the core concept of spt. in addition, pat, paedctas, and pediatric septic shock early warning signs protocol of the hospital were used for further modifications and to set the high-risk situations and vital signs. based on the final developed model (figure 1), pediatric patients arriving at the ed should be rapidly assessed by the triage nurses using pat. an abnormal pat or the need for lifesaving intervention according to esi version 4.0 led the patients to be categorized in pediatric triage level 1, who would immediately see the emergency physician (ep). pediatric patients with high-risk situations or abnormal vital signs according to the paedctas and the pediatric septic shock early warning signs protocol of the hospital were categorized in pediatric triage level 2 and would see the ep within 10 minutes. pediatric patients with normal vital signs without highrisk characteristics were categorized according to the predicted number of resources for diagnosis and management. pediatric patients with a prediction of ≥2 resources needed were categorized in triage level 3 and waited to see the ep within 60 minutes. pediatric patients with a prediction of one resource needed were categorized in triage level 4, and those with a prediction of no resources needed were categorized in triage level 5. the waiting times in pediatric triage levels 4 and 5 were not guaranteed, but the triage nurses re-evaluated the patients to detect clinical deterioration during the waiting time. spt content validity was acceptable and the model was approved by the emergency physicians, pediatric emergency physician, and the pediatric critical care physician. the inter-rater reliability of spt was evaluated using a scenariobased test, which yielded a kappa value of 0.65. 2.3. validation phase 2.3.1. participants patients younger than 15 years who visited the ed were enrolled in this study. patients excluded from the study were those scheduled for follow-up, those who were referred from other hospitals, and patients with incomplete medical records. 2.3.2. study protocol before implementation of the pediatric triage, all triage nurses were trained and passed an examination regarding triage using spt. the specific competency of the triage nurse consisted of experience working in the ed for more than 5 years and being well-trained in triage and advanced life support. pediatric patients were registered and assessed by the triage nurses. the nursing records were completed as much as possible with the basic information of the patients in addition to the initial assessment, chief complaint, signs, symptoms, and vital signs. the pediatric triage level was determined by the triage nurse using spt (figure 1) before seeing the physician. after completing the evaluation and treatment, the number of resources used including life-saving interventions, the final disposition, and diagnoses of the physicians were also recorded. over-triage was defined as patients in pediatric triage levels 1, 2, or 3 who used <2 resources, or pediatric triage level 1 patients who were not admitted to the hospital (6). the definition of under-triage in this study consisted of patients in pediatric triage level 2 with an abnormal pat or the need for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e39 an immediate life-saving intervention, patients in pediatric triage level 3 with abnormal vital signs or high-risk situations, and patients in pediatric triage level 4 or 5 who used ≥2 resources or were admitted to the hospital. 2.3.3. data gathering the data collected from the medical records included the patients’ baseline characteristics, arrival time, workday or weekend, mode of ed arrival, underlying diseases, chief complaint, initial vital signs, pediatric triage level, waiting time to see an ep, resources used, time and type of disposition, and final diagnosis. also recorded were the factors that affected appropriate triage, such as overcrowding, which were the results from the national ed overcrowding study score (11), and the experience of the triage nurse. 2.3.4. outcome measurements the primary outcome was the validity of the pediatric triage to predict ed death, hospitalization, and resource utilization. the secondary outcome was evaluating the factors associated with inappropriate triage (overor under-triage). 2.3.5. statistical analysis the data were entered into epidata manager (version 4.4.2.1) and the statistical analysis was conducted using r software (version 3.5.1). the sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), and the rates of overand under-triage were calculated. continuous variables were analyzed and reported as median and interquartile range, while numeric variables were reported as percentage. all data had non-parametric frequency distributions. continuous variables were compared using kruskalwallis one-way analysis of variance (anova). numeric variables were compared using the chi-square test. significant factors associated with appropriateness of triage were identified using odds ratio. screening performance characteristics of spt model were calculated as follows: the sensitivity (ratio of admitted patients or deaths in the ed in pediatric triage levels 1–3 and the total number of admitted patients or deaths in the ed), specificity (ratio of discharged patients in pediatric triage levels 4–5 and the total number of discharged patients), ppv (ratio of admitted patients or deaths in the ed for pediatric triage levels 1–3 and the number of patients in these levels), npv (ratio of discharged patients of pediatric triage levels 4–5 and the number of patients in these levels). 3. results 3.1. baseline characteristic of studied cases a total of 546 pediatric patients visited the ed during the study period. twenty-six patients were referred from other hospitals and were excluded. the number of patients who met the inclusion criteria was 520. the median age of the pediatric patients was 36 (12–84) months and 53.7% were boys. two hundred and eighty-eight (55.4%) patients visited the ed during the evening shifts and 284 (54.6%) patients presented during the workdays. the mode of arrival was most commonly walk-in, which was recorded for 498 (95.8%) patients. the percentage of non-traumatic chief complaints was 81.7%. the common chief complaints were fever (38.3%), dyspnea (12.5%), nausea and vomiting (7.9%), trauma related to the musculoskeletal system (7.3%), and abdominal pain (4.8%). no deaths were reported during the study. 3.2. screening performance characteristics of spt the sensitivity, specificity, ppv, and npv of spt were calculated as 98.28% (95%ci: 93.91–99.79), 26.24% (95%ci: 22.01–30.82), 27.67% (95%ci: 26.43–28.95), and 98.15% (95%ci: 93.00–99.53), respectively. 3.3. appropriateness of triage using spt the situation of resource consumption and final disposition in the different spt levels are presented in tables 1 and 2. the percentage of patients who were triaged appropriately was 68.7%, while 28.6% were over-triaged and 2.7% were undertriaged. under-triage occurred in pediatric triage levels 2, 3, and 4 in 3, 1, and 10 patients, respectively. the definitive diagnoses in under-triaged patients were fracture (3 patients), anaphylaxis (2 patients), acute gastroenteritis (2 patients), septic shock (1 patient), vomiting with dehydration (1 patient), wheezing associated with respiratory infection (1 patient), dengue fever (1 patient), acute appendicitis (1 patient), acute bronchitis (1 patient), and urinary tract infection (1 patient). over-triage occurred in pediatric triage level 2 (63 patients) and pediatric triage level 3 (86 patients). the common definitive diagnoses in over-triaged patients were acute gastroenteritis (22.6%), common cold (13.5%), dehydration (12.0%), acute febrile illness (11.3%), and limb injury (6.8%). underlying disease of respiratory system, fever, dyspnea, diarrhea, oxygen saturation <95%, accessory muscle use, and wheezing or rhonchi in lung sounds were significantly associated with triage appropriateness (tables 3 and 4). 4. discussion due to the high sensitivity and npv of spt, most of the highurgency patients were rapidly detected and most patients with a low level of urgency truly had non-urgent conditions. these results implied that spt is a good screening tool for most urgent cases and indicated a high probability of detecting actual non-urgent patients in pediatric triage levels 4 and 5. low specificity indicates that few patients with non-urgent conditions were correctly detected and is represented by the high rate of over-triage. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and et al. 4 special considerations that affect triage in pediatric patients are age-specific vital signs and the limited development of communication. in a study by cooper et al. (12), 1130 triage decisions based on history, visual cues, limited physical examination, and incomplete vital signs should have been revised. seventy percent of these changes were to a more urgent level and 20.7% of the patients were under 15 years old. categorizing the patient in a less urgent level due to incomplete assessment resulted in longer waiting times, which affected patient safety (13). this study showed that oxygen saturation was associated with appropriateness of the triage decision and this measurement was missed in only 4.6%. chief complaints such as fever and diarrhea need to be carefully evaluated, because these conditions affect the vital signs and result in tachycardia or tachypnea, which increase the rate of over-triage. however, tachycardia in a pediatric patient can be caused by either serious or non-serious conditions. tachycardia is an early sign of shock but non-specific conditions such as crying and fever may also be the cause. if the triage nurse strictly follows the protocol, the rate of overtriage will increase. this is an acceptable issue for patient safety. the rate of hospital admission in each level from 1 to 5 of this study and the previous study in songklanagarind hospital (8) were 100%, 31.6%, 16.8%, 2%, and 0% and 57.1%, 21%, 42.2%, 1.4%, and 3.6%, respectively. therefore, as a triage tool, spt showed greater validity. the percentage of patients in each level from 1 to 5 who needed more than one resource decreased and resource consumption increased from level 1 to 5. the data also presented correlated outcomes of hospital admission and resource utilization across the five levels of urgency, which were comparable to a previous systematic review of standard triage tools by de magalhães-barbosa et al. (6). even though the ed uses the same standard international triage tool, the validity of a triage tool can vary. based on institutional studies, development of the spt, which is compatible with specific patient characteristics and the local health system, permitted high validity and appropriate resource utilization. 5. limitations a limitation of this study was that the admission rates of modified esi and pediatric triage were compared in different populations. another limitation was the lack of information on whether the patients were admitted to other healthcare facilities after leaving the ed. 6. conclusion spt showed good correlation of hospital admission rates and resource utilization with pediatric triage level of urgency. however, further efforts are needed to decrease the rates of overand under-triage. further discussion between the experts and multidisciplinary team is needed for quality improvement. 7. declarations 7.1. acknowledgments the authors thank kingkarn waiyanak for searching for articles and retrieval. the authors thank teeranai sakulchit md, pediatric emergency physician, department of emergency medicine and kantara saelim md, division of pulmonary and critical care, department of pediatrics for reviewing the triage protocol. the authors also thank glenn k. shingledecker for his help in editing the english of the manuscript. 7.2. author contribution nut chonwanich performed the literature research, study design, data collection, data analysis, data interpretation, and writing the manuscript. wannipha senuphai did data collection, data analysis, and data interpretation. siriwimon tantarattanapong did the study design, data analysis, data interpretation, critical revision, and writing the manuscript. the authors contributed to data analysis, drafting, and the critical revisions of the paper and agree to be accountable for all aspects of the work. 7.3. funding sources the faculty of medicine, prince of songkla university funded this research. 7.4. conflict of interest the authors declare they have no conflict of interest. references 1. physicians acoe. crowding 2019 [available from: https://www.acep.org/patient-care/policystatements/crowding/. 2. mcnally s. let’s have standards for triage education and practice. australian emergency nursing journal. 2001;4(2):12-4. 3. patel vl, gutnik la, karlin dr, pusic m. calibrating urgency: triage decision-making in a pediatric emergency department. advances in health sciences education. 2008;13(4):503-20. 4. baumann mr, strout td. evaluation of the emergency severity index (version 3) triage algorithm in pediatric patients. academic emergency medicine. 2005;12(3):219-24. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e39 5. mor m, waisman y. triage principles in multiple casualty situations involving children: the israeli experience. pediatric emergency medicine database (serial online). 2002. 6. de magalhães-barbosa mc, robaina jr, prata-barbosa a, de souza lopes c. validity of triage systems for paediatric emergency care: a systematic review. emergency medicine journal. 2017;34(11):711-9. 7. hinson js, martinez da, schmitz ps, toerper m, radu d, scheulen j, et al. accuracy of emergency department triage using the emergency severity index and independent predictors of under-triage and over-triage in brazil: a retrospective cohort analysis. international journal of emergency medicine. 2018;11(1):1-10. 8. wuthisuthimethawee p, boonchai p. validity and reliability of the modified emergency severity index (esi) version 4 for pediatric triage in the emergency department, songklanagarind hospital, thailand. journal of the medical association of thailand. 2019;102(4):449-54. 9. dieckmann ra, brownstein d, gausche-hill m. the pediatric assessment triangle: a novel approach for the rapid evaluation of children. pediatric emergency care. 2010;26(4):312-5. 10. warren dw, jarvis a, leblanc l, gravel j, group cnw. revisions to the canadian triage and acuity scale paediatric guidelines (paedctas). canadian journal of emergency medicine. 2008;10(3):224-32. 11. weiss sj, derlet r, arndahl j, ernst aa, richards j, fernández-frankelton m, et al. estimating the degree of emergency department overcrowding in academic medical centers: results of the national ed overcrowding study (nedocs). academic emergency medicine. 2004;11(1):38-50. 12. cooper rj, schriger dl, flaherty hl, lin ej, hubbell ka. effect of vital signs on triage decisions. annals of emergency medicine. 2002;39(3):223-32. 13. di martino p, leoli f, cinotti f, virga a, gatta l, kleefield s, et al. improving vital sign documentation at triage: an emergency department quality improvement project. journal of patient safety. 2011;7(1):26-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and et al. 6 table 1: numbers of resources consumed in different levels of the songklanagarind pediatric triage triage level ≥2 resources 1 resource 0 resource 1 (n = 10) 10 (100) 0 0 2 (n = 247) 156 (63.2) 73 (29.6) 18 (7.3) 3 (n = 155) 67 (43.2) 66 (42.6) 22 (14.2) 4 (n = 100) 10 (10.0) 56 (56.0) 34 (34.0) 5 (n = 8) 0 (0.0) 2 (25.0) 6 (75.0) data are presented as number (%). table 2: songklanagarind pediatric triage level and disposition triage level hospitalization discharge total icu ward ed or 1 (n = 10) 10 (100) 4 (40.0) 6 (60.0) 0 (0.0) 0 (0.0) 2 (n = 247) 78 (31.6) 3 (1.2) 75 (30.4) 0 (0.0) 169 (68.4) 3 (n = 155) 26 (16.8) 0 (0.0) 24 (15.5) 2 (1.3) 129 (83.2) 4 (n = 100) 2 (2.0) 0 (0.0) 2 (2.0) 0 (0.0) 98 (98.0) 5 (n = 8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100.0) data are presented as number (%). icu: intensive care unit; ed: emergency department; or, operation room. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e39 table 3: associated factors of appropriate (n = 357) and inappropriate (n = 163) triage variable appropriate inappropriate p male 189 (52.9) 90 (55.2) 0.698 age, median (iqr), months 36 (12, 84) 36 (12, 84) 0.536 thai ethnicity 356 (99.7) 162 (99.4) 0.529 work shift morning shift 85 (23.8) 43 (26.4) 0.739 evening shift 198 (55.5) 90 (55.2) night shift 74 (20.7) 30 (18.4) workday 196 (54.9) 88 (54.0) 0.921 ed arrival by self-transport 340 (95.2) 158 (96.9) 0.742 underlying disease 93 (26.1) 29 (17.8) 0.051 trauma cause 70 (19.6) 25 (15.3) 0.295 non-trauma cause 287 (80.4) 138 (84.7) chief complaint fever 123 (34.5) 76 (46.6) 0.011 dyspnea 60 (16.8) 5 (3.1) <0.001 nausea and vomiting 23 (6.4) 18 (11.0) 0.103 abdominal pain 14 (3.9) 11 (6.7) 0.239 diarrhea 6 (1.7) 10 (6.1) 0.014 seizure 9 (2.5) 1 (0.6) 0.183 alteration of consciousness 2 (0.6) 0 1.000 abnormal primary assessment triangle (pat) airway problem 6 (1.7) 0 na abnormal breathing 4 (1.1) 0 abnormal circulation 0 0 vital signs in triage area body temperature 345 (96.6) 159 (97.5) 0.778 systolic blood pressure 344 (96.4) 158 (96.9) 0.941 pulse rate 353 (98.9) 163 (100) 0.314 respiratory rate 339 (95.0) 155 (95.1) 1.000 oxygen saturation 339 (95.0) 157 (96.3) 0.645 sao2 <95% 26 (7.7) 4 (2.5) 0.043 crying# 46 (12.9) 20 (12.3) 0.526 accessory muscle use 23 (6.4) 3 (1.8) 0.044 wheezing, rhonchi 85 (23.8) 7 (4.3) <0.001 full pulse 356 (99.7) 163 (100) 1.000 full consciousness 348 (97.5) 159 (97.5) 1.000 nurses’ experience (>10 years) 220 (61.6) 108 (66.3) 0.359 overcrowding* 211 (59.1) 96 (58.9) 1.000 *: numbers of patients visited during overcrowding periods. #: crying during vital signs measurement. data are presented as number (%) unless otherwise indicated. morning shift 8:00 am–4:00 pm; evening shift 4.00 pm–0:00 am; night shift 0:00 am–8:00 am. iqr: interquartile range; ed: emergency department. table 4: odds ratios of factors associated with appropriateness of triage variable odds ratio 95%ci underlying disease of respiratory system 4.16 (1.75–9.23) fever 0.60 (0.41–0.88) dyspnea 6.38 (2.51–16.22) diarrhea 0.26 (0.09–0.73) sao2 <95% 3.18 (1.09–9.27) accessory muscle use 3.67 (1.09–12.41) wheezing or rhonchi 6.96 (3.14–15.43) ci: confidence interval; sao2: oxygen saturation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and et al. 8 figure 1: songklanagarind pediatric triage. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e36 rev i ew art i c l e clinical scoring systems in predicting the outcome of acute upper gastrointestinal bleeding; a narrative review hanieh ebrahimi bakhtavar1, hamid reza morteza bagi1, farzad rahmani1,2 ∗, kavous shahsavari nia1, arezu ettehadi1 1. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. 2. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. received: november 2015; accepted: january 2016; published online: 11 january 2017 abstract: prediction of the outcome and severity of acute upper gastrointestinal bleeding (ugib) has significant importance in patient care, disposition, and determining the need for emergent endoscopy. recent international recommendations endorse using scoring systems for management of non-variceal ugib patients. to date, different scoring systems have been developed for predicting the risk of 30-day mortality and re-bleeding. we have discussed the screening performance characteristics of baylor bleeding score, the rockall risk scoring score, cedars-sinai medical center predictive index, glasgow blatchford score, t-score, and aims65 systems, in the present review. based on the results of this survey, there are only 3 clinical decision rules that can predict the outcome of ugib patients, independent from endoscopy. among these, only glasgow blatchford score was highly sensitive for predicting the risk of 30-day mortality and re-bleeding, simultaneously. keywords: hemorrhage; upper gastrointestinal tract; prognosis; mortality; decision support techniques © copyright (2017) shahid beheshti university of medical sciences cite this article as: ebrahimi bakhtavar h, morteza bagi hr, rahmani f, shahsavari nia k, ettehadi a. clinical scoring systems in predicting the outcome of acute upper gastrointestinal bleeding; a narrative review. 2017; 5(1): e36. 1. introduction p rediction of the outcome and severity of upper gastrointestinal bleeding (ugib), with 10% mortality rate, has significant importance in patientcare, disposition, and determining the need for emergent endoscopy (1, 2). some clinical criteria such as hemodynamic and mental status, volume of blood lost, and coagulopathy profile were used in determining the patient’s outcome (3). in addition, early upper gastrointestinal endoscopy, within the first 24 hours of emergency department (ed) arrival, is recommended for treatment as well as outcome prediction of these patients (1). clots adhering to the ulcer, visible bleeding, and visible vessel in the ulcer are associated withhigh probability of rebleeding. on the other hand, brown or black pigments on the ulcer andclean based ulcerare associated with high probability of re-bleeding (3, 4). endoscopic triage of these patients ∗corresponding author: farzad rahmani; emergency department, emergency medicine department, sina medical research and training hospital, tabriz university of medical sciences, tabriz, iran; tel: 00984135498144, fax: 00984135412151, email: rahmanif@tbzmed.ac.ir. could reduce duration of hospital stay and costs, but due to lack of endoscopy devices and absence of interventionists, it is not obtainable in the majority of eds (5). to date, different clinical scoring systems have been developed to predict the outcome and guide the management and disposition of these patients (3, 6). recent international recommendations regarding management of non-variceal ugib patients endorse using these systems for risk stratification in the first visit. table 1 and 2 show the sensitivity, specificity, ppv (positive predictive value), npv (negative predictive value) of 6 scoring system in the prediction of 30 days mortality and rebleeding (7), (8), (9). hereby, 6 of these scoring systems and their screening performance characteristics will be discussed comprehensively. 2. endoscopy dependent scoring systems 2.1. baylor bleeding score (bbs) this scoring system was introduced by saeed za et al, in 1993. they designed it for predicting the risk of re-bleeding in patients with ugib (table 3). this scoring system contains this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com rahmanif@tbzmed.ac.ir h. ebrahimi bakhtavar et al. 2 table 1: screening performance characteristics of scoring systems in predicting re-bleeding risk in upper gastrointestinal bleeding scores sensitivity specificity ppv npv gbs 1.00 0.12 0.07 1.00 bbs 1.00 0.26 0.10 1.00 csmcpi 0.88 0.32 0.10 0.97 rs 1.00 0.28 0.10 0.99 aims65 0.35 0.82 0.89 0.23 ppv: positive predictive value, npv: negative predictive value, gbs: glasgow blatchford score, bbs: baylor bleeding score, csmcpi: cedars-sinai medical center predictive index, rs: rockall risk scoring score. table 2: screening performance characteristics of scoring systems in predicting 30-day mortality in upper gastrointestinal bleeding scores sensitivity specificity ppv npv gbs 0.97 0.13 0.14 0.97 bbs 0.97 0.27 0.14 0.98 csmcpi 0.97 0.29 0.15 0.99 rs 0.96 0.27 0.14 0.98 t score 0.71 0.80 0.78 0.73 aims65 0.35 0.82 0.89 0.23 ppv: positive predictive value, npv: negative predictive value, gbs: glasgow blatchford score, bbs: baylor bleeding score, csmcpi: cedars-sinai medical center predictive index, rs: rockall risk scoring score. three parts, namely pre-endoscopy, during endoscopy, and post-endoscopy. the score of ≥ 6 in the pre-endoscopy part and ≥ 11 in the total score have 100% sensitivity for predicting the risk of re-bleeding (10, 11). in another research in 1995, the same authors indicated that the score of ≤ 5 before endoscopy and ≤ 10 after endoscopy are associated with low re-bleeding risk. they finally revealed that bbs determines high-risk patients prone to re-bleeding after successful hemostatic endoscopy with high accuracy (12). 2.2. rockall risk scoring score (rs) rockall et al. introduced rs system in 1997. this score consists of two parts: pre-endoscopy, also known as clinical rockall score, and post-endoscopy, which is called the rockall risk score (table 4). they figured out that as the score increases, the chance of mortality or re-bleeding increases (2, 13). different studies indicated that this system is practical, accurate, and a quick tool in prediction of re-bleeding and mortality risk (14-16). evaluating the system in patients with non-variceal ugib, rahman mw showed that the score of ≤ 3 predicts low risk, while ≥ 8 is a predictor of high mortality risk. they also revealed the good performance index of rs system in ugib patients triage(17). 2.3. cedars-sinai medical center predictive index (csmcpi) this scoring system has been introduced according to the suggestions by american society of endoscopy of the digestive system in 1981 (18). it consists of four sections (table 5). the first one was related to endoscopic findings, the second dealt with the time interval between symptom initiation and hospitalization, the third section was related to the hemodynamic status of the patient, and finally the fourth section was related to the number of comorbidities. the total score of the patient was the sum of scores obtained from these four sections (18, 19). patients with a score < 3 can be discharged from ed and others need hospitalization. these patients are re-evaluated after 24-72 hours based on endoscopy results. a validation study in 1997 showed that application of this scoring system with great accuracy, can lead to decreased duration of hospital stay (20). 3. clinical scoring systems (independent from endoscopy) 3.1. glasgow blatchford score (gbs) blatchford et al. studied the mortality rate of 1882 ugib patients previously under gone endoscopy to introduce a new scoring system for predicting ugib patient’s need for therapeutic interventions and blood transfusion as well as mortality risk, re-bleeding, and dropped hemoglobin levels after hospitalization (table 6) (21). a study evaluating the validity of this score in 2000 showed that patients with a score of zero belong to the low-risk group, and can be discharged from ed (22). stanley et al. compared gbs and rs in a multicenter study and concluded that none of the patients categorized as low risk in the gbs scoring system, needed intervention during hospitalization and no mortality was observed in this this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e36 table 3: baylor bleeding score and interpretation score pre-endoscopy score (range: 0-15) endoscopy score(range: 0 9) age(years) no. of illnesses severity of illnesses site of bleeding stigmata of bleeding 0 < 30 0 1 30 49 1 or 2 clot 2 50 59 3 60 69 visible vessel 4 3 or 4 chronic posterior bulb 5 ≥ 70 ≥5 acute active bleeding total score is the sum of scores obtained for each item, which ranges from 0 to 24. score ≥ 6 in pre-endoscopic phase and total score ≥ 11 indicate high-risk patients for re-bleeding. example: a 34-year-old patient (score: 1) with chronic (score: 4) hepatic failure (score: 1) and adhering clot (score: 1) on ulcer in endoscopy has a score of 7 (1 + 4 + 1+ 1). table 4: rockall risk scoring score and interpretation variable score 0 1 2 3 age (year) < 60 60–79 ≥ 80 shock stage sbp (mmhg) ≥ 100 ≥ 100 < 100 pr (1/minute) < 100 ≥ 100 comorbidity no major comorbidity cardiac failure, ischemic heart disease, any major comorbidity renal failure, liver failure, disseminated malignancy diagnosis mallory-weiss tear, no lesion identified and no srh all other diagnosis malignancy of upper gi tract major srh none or dark spot only blood in upper gi tract, adherent clot, visible or spurting vessel spb: systolic blood pressure, pr: pulse rate, gi: gastrointestinal, srh: signs of recent hemorrhage. range of score is 0-11. score of ≤ 3 predicts low mortality risk, while ≥ 8 is a predictor of high mortality risk. table 5: cedars-sinai medical center predictive index and interpretation score endoscopic findings time∗ hemodynamics comorbidities 0 pud (no srh), malloryweiss tear (nb), erosive disease (no srh), normal finding > 48 stable ≤ 1 1 pud (spot/clot), erosive disease (srh), angiodysplasia < 48 intermediate 2 2 pud (vvnb/srh) in hospital unstable 3 3 ≥ 4 4 persistent ugih, varices, ugi cancer ∗ time means the interval between the initiation of bleeding and arrival to emergency department (hour), nb: non-bleeding, pud: peptic ulcer disease, srh: signs of recent hemorrhage, ugi: upper gastrointestinal, ugih: upper gastrointestinal hemorrhage, vvnb: visible vessel, non-bleeding. score range is 0 to 11. patients with a score < 3 can be discharged from ed and others need hospitalization. the criteria of hemodynamic classification was not clearly defined. group. eventually, the authors concluded that application of gbs can contribute to reducing hospitalization rate and costs in low-risk patients (23). 3.2. modified glasgow blatchford score (mgbs) d.w. cheng et al introduced a modified type of gbs system (mgbs). in this system, three variables related to syncope, melena, and comorbidities were omitted from the gbs, and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. ebrahimi bakhtavar et al. 4 table 6: glasgow blatchford score admission risk markers score blood urea nitrogen level (m g /d l ) ≥ 18.2t o < 22.4 2 ≥ 22.4t o < 28 3 ≥ 28t o < 70 4 ≥ 70 6 hemoglobin level for men (g /d l ) ≥ 12t o < 13 1 ≥ 10t o < 12 3 < 10 6 hemoglobin level for women (g /d l ) ≥ 10t o < 12 1 <10 6 systolic blood pressure (mmhg) ≥ 100t o < 109 1 ≥ 90t o < 99 2 < 90 3 other markers pulse rate ≥ 100 beats/min 1 presentation with melena 1 presentation with syncope 2 hepatic disease∗ 2 heart failure] 2 ∗ known history, or clinical and laboratory findings of chronic or acute hepatic disease. ] known history, or clinical and echocardiographic findings of heart failure. range of score is 0-29. score > 0 is high-risk group. the new scoring system was introduced based on the status of clinical and laboratory findings and patient symptoms. they concluded that the mgbs score could predict the outcome of patients with high accuracy. it is also more convenient to use compared to gbs (2). 3.3. t-score system t-score system was designed based on the clinical status of ugib patients before performing endoscopy (table 7). patient’s general appearance, number of comorbid diseases, pulse rate, systolic blood pressure, and hemoglobin level are among t score variables. a score <6 indicates high-risk status (t1), a score between 7 and 9 shows moderate-risk status (t2), and a score of ≥ 10 reveals low-risk status (t3). good clinical conditions include a patient without weakness or orthostatic hypotension who have ≤ 1comorbidity. validation studies concluded that this score could determine the need of ugib patients for early endoscopy with an accuracy equal to gbs (9, 24). 3.4. aims65 system recently, a simple score was introduced by saltzman jr et al. for evaluating the prognosis of ugib patients. it includes five variables: age over 65, systolic blood pressure lower than 90 mmhg, altered level of consciousness, international normalized ratio (inr) higher than 1.5, and serum albumin lower than 3 g/dl. the patient would receive one score for presence of each variable. eventually, mortality rate was estimated to be 0.3% for score 0, 1.2% for score 1, 5.3% for score 2, 10.3% for score 3,16.5% for score 4, and 24.5% for score 5. scores of 0-1 and 2-5 are related to low-risk and high-risk patients, respectively. saltzman jr et al.concluded that this score has high accuracy in prediction of in-hospital mortality, length of hospital stay, and reduction of the hospitalization cost in patients with ugib (5). hyett bh et al. compared aims65 and gbs and concluded that aims65 is more accurate in prediction of mortality in comparison with gbs, while gbs is more accurate in estimation of need for blood transfusion. both scores were similar in prediction of other outcomes (25). yaka e et al. also compared aims65 and gbs, and concluded that gbs has a lower sensitivity in predicting the need for emergent intervention in comparison with aims65 (5). 4. discussion in this narrative review, we evaluated 6 different scoring systems to predict the outcome of patients with acute ugib. each of these systems used different variables in predicting the outcome of acute ugib patients. based on the findings of this review, only aims65, gbs, and t score were designed to determine the outcome of ugib patients without needing emergency endoscopy. furthermore, only aims65 score determines the outcome of patients disregarding comorbidities and only based on the patient’s current clinical status. some researchers want to predict the patient’s outcome without considering the comorbidities or even endoscopy results, so they have modified some scoring system such as gbs or clinical rockall score. a weak point of csmcpi score was that definition of hemodynamic status was vague in this system (8). table 1 and 2 summarize the screening performance characteristics of these scoring systems in the risk prediction of re-bleeding and 30-day mortality. in the case of predicted probability of re-bleeding, rs, bbs, and csmcpi have similar values and these systems do not have any significant differences in prediction of re-bleeding, but aims65 score has a higher specificity and positive predictive value(82%, and 89% respectively), in this regard. these characteristics represent the great value of this system compared to others. in addition, aims65 and t score have the same value in predicting 30-day mortality. another difference of aims65 with other systems is that, unlike the others, it only assesses the current clinical status of the patient, regardless of underlying diseases. despite the presence of all these scoring systems, none is routinely used in emergency departments. this might be due to various reasons such as lack of valithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e36 table 7: t-score clinical parameter score 1 2 3 general conditions poor intermediate good pulse (beats/minute) > 110 90–110 < 90 systolic blood pressure (mmhg) < 90 90 – 110 > 110 hemoglobin levels (g/dl) ≤ 8 9– 10 > 10 general condition was defined based on the patient’s number of comorbidities. poor condition was associated with ≤3 comorbidities or impending to shock. good condition means a patient is without weakness or orthostatic hypotension and has ≤ 1 comorbidity. intermediate condition includes patients with conditions between the mentioned two groups. a score < 6 indicates high-risk (t1), a score between 7 and 9 shows moderate-risk (t2), and a score of ≥ 10 reveals low-risk patients (t3) for detection of major findings in endoscopy. dation studies, not being user-friendly, and not believing in evidence-based medicine. it seems that we need further validation studies prior to implementing these clinical decision rules in our routine practice. 5. conclusion based on the results of this survey, there are only 3 clinical decision rules that can predict the outcome of ugib patients, independent from endoscopy. among these, only glasgow blatchford score was highly sensitive for predicting the risk of 30-day mortality and re-bleeding simultaneously. 6. appendix 6.1. acknowledgements none 6.2. authors contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding support none 6.4. conflict 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gastrointestinal haemorrhage. alimentary pharmacology & therapeutics. 2011;34(4):4705. 24. tammaro l, di paolo mc, zullo a, hassan c, morini s, caliendo s, et al. endoscopic findings in patients with upper gastrointestinal bleeding clinically classified into three risk groups prior to endoscopy. world journal of gastroenterology: wjg. 2008;14(32):5046. 25. hyett bh, abougergi ms, charpentier jp, kumar nl, brozovic s, claggett bl, et al. the aims65 score compared with the glasgow-blatchford score in predicting outcomes in upper gi bleeding. gastrointestinal endoscopy. 2013;77(4):551-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction endoscopy dependent scoring systems clinical scoring systems (independent from endoscopy) discussion conclusion appendix references emergency. 2017; 5 (1): e6 or i g i n a l re s e a rc h risk factors of non-fatal unintentional home injuries among children under 5 years old; a population-based study sedigheh nouhjah1,2, sharareh r. niakan kalhori1,3∗, azadeh saki4 1. social determinants of health research center, school of health, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. health research institute, diabetes research center, ahvaz jundishapur university of medical sciences, ahvaz, iran. 3. department of health information management, school of allied medical sciences, tehran university of medical sciences, tehran, iran. 4. department of biostatistics, school of health, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: september 2015; accepted: april 2016; published online: 8 january 2017 abstract: introduction: in addition to the annual mortality rate, unintentional home injury may result in temporary or permanent disability and requires medical attention and continuous care in millions of children. this study aimed to explore features and risk factors of these injuries. methods: in this cross-sectional study, demographic variables and epidemiologic pattern of home injuries among children under 5 years of age were collected via a population-based survey in seven main cities of khuzestan province, southwest iran, during september 2011 to december 2012. developing a risk stratification model, independent risk factors of unintentional home injury were determined and put to multivariate logistic regression analysis. results: 2693 children with the mean age of 27.36 ± 15.55 months (1 to 60) were evaluated (50.9% boy). 827 (30.7%) cases had a history of at least one home injury occurrence since birth to study time. the most common injury mechanisms were burning with 291 (38.4%) cases, falling with 214 (28.3%) and poisoning with 66 (8.7%) cases, respectively. the independent risk factors of unintentional home injury were age ≥ 24 month (p<0.001), residency in ahvaz city (p<0.001), mother’s illiteracy (p<0.014), ethnicity (p<0.001), private housing (p=0.01), birth weight (p<0.001), and being the first child (p=0. 01). sensitivity, specificity, and area under the roc curve of the model designed by multivariate analysis were 53.5%, 84.8%, and 0.75 (95% ci: 0.730.77; p < 0.001, figure 1), respectively. conclusion: according to the findings of this study, 30.7% of the studied children were injured at least once since birth. burning, falling, poisoning, swallowing objects, choking, and biting were the main home injury mechanisms. age ≥ 24 months, being the first child, living in a private house, being a resident of ahvaz city, and having an illiterate mother were found to be risk factors of home injury. keywords: home injuries; child, preschool; risk factors; injury prediction; risk reduction © copyright (2017) shahid beheshti university of medical sciences cite this article as: nouhjah s, r. niakan kalhori sh, saki a. risk factors of non-fatal unintentional home injuries among children under 5 years old; a population-based study. emergency. 2017; 5 (1): e6. 1. introduction alteration in epidemiological pattern of childhood mortality, progress in control of infectious diseases, and increased risk of injuries have created a new view of child mortality ∗corresponding author: sharareh r. niakan kalhori; social determinants of health research center, school of health, ahvaz jundishapur university of medical sciences, ahvaz, iran. tel: 09226067462, +98 21 8898278; email: niakan2@gmail.com and morbidity in the world (1). injury is a major cause of death from childhood to 10-19 years old (1, 2). in addition to the annual mortality rate, injury may result in temporary or permanent disability and requires medical attention and continuous care in millions of children (3). about 95% of child injuries and more than 80% of related deaths occur in low and middle-income countries (1, 4). about 90% of child deaths resulting from injuries or violence, occur due to unintentional injuries (1). unintentional injuries may influence health, education, and family economy of the affected children (3). most unintentional childhood this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. nouhjah et al. 2 injuries take place in the home, where children spend a long period of their time and are supposed to be well supervised; however, they are exposed to various injury hazards (5-7). the most common injury mechanisms have been reported as falling, burning, swallowing, poisoning, choking, biting and drowning in a variant order (3, 8). in the current care system, the same process is used to prevent every type of injury mechanism among children under the age of 5 years, which is mainly brief education for their mothers. screening children who are at a higher risk of home injury based on their epidemiologic features is a fantastic idea for preventing home injuries, efficiently. children can be classified based on their potential risk of home injury and their mother can then be educated on factors that might categorize the child as prone to a specific injury mechanism. currently, there is a lack of patterns related to child injury and available researches are mainly hospital-related works. since only a limited number of child home injuries lead to hospitalization, this type of investigation may ignore small and limited emergencies. middle or small scale injures that need temporary therapeutic interventions may not be registered anywhere and recently this limitation has received more attention than before. thus, this population-based study aimed to explore features and risk factors of non-fatal unintentional home injuries among children under 5 years old in khuzestan province of iran. 2. methods 2.1. study design and setting in this cross-sectional study, data were collected via a population-based survey of home injuries for children under 5 years of age in seven main cities of khuzestan province, southwest iran, during september 2011 to december 2012. selected cities included ahvaz, andimeshk, khoramshahr, shoush, baghmalek, behbahan, and ramshir, which were the most populated places in terms of children under care. ahvaz is the capital of khuzestan province and has a number of different ethnic groups; the others are also main cities with different socioeconomic, cultural and ethnic groups. in each city 4-8 health centers were randomly selected based on covered population. the who guideline for external injury was used for coding and classifying the data. before data collection, the study’s ethical approval was obtained from ahvaz jundishapur medical university ethical research committee under ethics number eth-684. in addition, the aim of study was explained to study cases and researchers adhered to data confidentiality. 2.2. participants children under 5 years old seeking routine care were included using a multistage cluster sampling method. their mothers were asked about their offspring’s experience of non-fatal unintentional home injuries since birth. cases related to intentional home injuries such as interpersonal violence, domestic abuse, child abuse, self-inflicted harm, or crime, as well as injuries leading to death or occurring outside the home were excluded. 2.3. data gathering parent-related data (their age, job, education level, ethnicity), mother’s pregnancy type (wanted, unwanted), family status (living with both parents or one of them, house type, number of children), child’s features (age, birth weight, gender, birth order, age when injured), whether a child suffered an injury during the last year and since birth, injury details (mechanism, frequency, season, time and place, activity at the time of occurrence, hospitalization or physician visit, duration of hospitalization, physical/mental disability, injured organ, person responsible for event), were recorded in a 63item questionnaire. it was designed using “who guideline for external injury” and confirmed through a pilot study conducted in ahvaz (9). the content validity of the research tool was verified by two experts including pediatrician and a statistician. its reliability was confirmed using cronbach’s alpha coefficient (0.81). data were gathered by a group of trained public health students. 2.4. statistical analysis data were analyzed using spss version 16. qualitative variables were reported as frequency and percentage, and quantitative ones as mean ± standard deviation. in the first step, independent risk factors of unintentional home injury among children under 5 years old were determined using univariate analysis. trying to develop a risk stratification model, independent variables of univariate analyses were put to multivariate logistic regression analysis. we used backwards elimination method for identifying risk factors of home injuries in 7 steps. screening performance characteristics of the model were reported (sensitivity, specificity, and area under receiver operating characteristics (roc) curve). p value < 0.05 was considered as level of significance. 3. results: 2693 children with the mean age of 27.36 ± 15.55 months (1 to 60) were evaluated (50.9% boy). table 1 summarizes baseline characteristics of studied population. 827 (30.7%) cases had a history of at least one home injury occurrence since birth to study time. the extremities were the injured part of body in more than 50% of cases and 68.8% (1852) of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e6 table 1: frequency of home injuries based on demographic features of less than 5 year’s children and their mother list of variables total n (%) history of home injury n (%) p value yes no gender male 1369 (50.9) 409(29.9) 960(70.1) 0.33 female 1322 (49.1) 418(31.6) 904(68.4) age group (month) 0-12 584 (21.7) 119(20.4) 465(79.6) 13-24 830 (30.8) 240(28.9) 590(71.1) 25-36 504 (18.7) 176(34.9) 328(65.1) <0.001 37-48 483 (17.9) 177(36.6) 306(63.4) 49-60 291 (10.8) 115(39.5) 176(60.5) city ahvaz 900 (33.4) 327 (36.3) 573(63.7) andimeshk 299 (11.1) 77(25.8) 222(74.2) behbahan 300 (11.1) 55(18.3) 245(81.7) khoram-shahr 299 (11.1) 157(52.5) 142(47.5) <0.001 ramshir 300 (11.1) 72(24.0) 228(76.0) shoush 300 (11.1) 51(17.0) 249(83.0) baghmalek 295 (11.0) 88(29.8) 207(70.2) mother’s job employed 159 (5.9) 45(28.3) 114(71.7) 0.50 housekeeper 2521 (94.1) 777(30.8) 1744(69.2) mother’s literacy illiterate 202 (7.6) 71 (35.1) 131(64.9) primary school 611 (22.9) 208(34.0) 208(34.0) middle school 701 (26.2) 200(28.5) 501(71.5) 0.014 high school 886 (33.2) 275(31.0) 611(69) academic 271 (10.1) 65(24.0) 206(76.0) mother’s ethnicity arab 1285 (49.0) 472(36.7) 813(63.3) fars 523 (20.0) 130(24.9) 393(75.1) <0.001 lore 707 (27.0) 177(25.0) 530(75.0) other 107 (4.0) 36(33.6) 71(66.4) type of house apartment 502 (26.0) 171(34.1) 331(65.9) 0.01 private 1431 (74.0) 581(40.6) 850(59.4) birth order 1 1343 (50.0) 438(32.6) 905(67.4) 2 859 (32.0) 248(28.9) 611(71.1) 0.01 3 322 (12.0) 86(26.7) 236(73.3) ≥4 163 (6.0) 54(33.1) 109(66.9) injuries occurred during playing. common mechanisms of home injuries based on demographic features of children and mothers are summarized in table 2. the most common injury mechanisms were burning with 291 (38.4%) cases, falling with 214 (28.3%), poisoning with 66 (8.7%), swallowing with 47 (6.2%), biting with 32 (4.2%), and chocking with 29 (3.8%), respectively. 341 (69.5%) of injured children needed medical visits and 143 cases (39.4%) were hospitalized. based on univariate analysis, the independent risk factors of unintentional home injury among children under 5 years old were age ≥ 24 month (p<0.001), residency in ahvaz city (p<0.001), mother’s illiteracy (p<0.014), ethnicity (p<0.001), private housing (p=0.01), birth weight (p<0.001), and being the first child (p=0. 01). table 3 shows the results of multivariate logistic regression analysis. the model’s sensitivity, specificity, and area under the roc curve were 53.5%, 84.8%, and 0.75 (95% ci: 0.730.77; p < 0.001, figure 1), respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. nouhjah et al. 4 table 2: common mechanisms of home injuries based on demographic features of under 5 year’s children and their mothers variable burning falling poisoning swallowing choking biting others gender male 151(39.7) 102(26.8) 30(7.9) 27(7.1) 15(3.9) 19(5.0) 36(9.5) female 140(37.1) 112(29.7) 36(9.5) 20(5.3) 14(3.7) 13(3.4) 42(11.1) age group (month) 0-12 36(31.6) 29(25.4) 6(5.3) 22(19.3) 5(4.4) 6(5.3) 10(8.8) 13-24 82(38.1) 59(27.4) 19(8.8) 13(6.8) 14(6.5) 8(3.7) 20(9.3) 25-36 70(43.2) 49(22.9) 18(27.3) 3(6.0) 2(6.9) 5(15.6) 15(19.2) 37-48 63(38.9) 44(20.6) 15(22.7) 6(3.7) 5(17.2) 8(25.0) 21(26,9) 49-60 40(38.5) 33(15.4) 8(12.1) 3(2.9) 6(12.8%) 3(10.3%) 12(15.4) city of residence ahvaz 100(37.3) 37(13.8 ) 30(11.2) 31(11.6) 11(14.1) 19(7.1) 40(14.9) andimeshk 17(22.1) 31(40.3) 9(11.7) 4(5.2) 10(13.0) 2(2.6) 4(5.2) behbahan 26(53.1) 11(22.4) 3(6.1) 0(0) 2(4.1) 0(0) 7(14.3) khoram-shahr 75(48.1) 58(37.2) 4(2.6) 3(1.9) 4(2.6) 0(0) 12(7.7) ramshir 39(54.9) 16(22.5) 2(2.8) 6(8.5) 1(1.4) 2(2.8) 5(7.0) shoush 5(9.8) 24(47.1) 12(23.5) 0(0) 0(0) 7(13.7) 3(5.9) baghmalek 29(34.1) 37(43.5) 6(7.1) 3(3.5) 1(1.2) 2(2.4) 7(8.2) mother’s job employed 272(38.4) 193(27.3) 65(9.2) 45(6.4) 26(3.7) 32(4.5) 75(10.6) housekeeper (42.2) 19(42.2) 1(2.2) 2(4.4) 3(6.7) 0(0.0) 3(6.7) mother’s literacy illiterate 24(34.8) 19(27.5) 7(10.1) 4(5.8) 3(4.3) 4(5.8) 8(11.6) primary school 88(45.4) 50(25.8) 13(6.7) 12(6.2) 4(2.1) 6(3.1) 21(10.8) middle school 62 (34.1) 60(33.0) 21(11.5) 6(3.3) 12(6.6) 9(28.1) 12(6.6) high school 95 (38.8) 62(25.3) 21(8.6) 19(7.8) 7(2.9) 11(4.5) 30(12.2) academic 19(31.1) 21(34.4) 3(4.9) 6(9.8) 3(4.9) 2(3.3) 7(11.5) mother’s ethnicity arab 180(41.5) 105(24.2) 37(8.5) 29(6.7) 14(3.2) 16(3.7) 53(12.2) fars 41(36.0) 33(28.9) 9(7.9) 10(8.8) 4(3.5) 6(5.3) 11(9.6) lore 50(30.7) 60(36.8) 18(11.0 ) 8(4.9) 9(5.5) 8(4.9) 10(6.1) other 17(47.2) 12(33.3 ) 2(5.6) 0(0) 2(5.6) 1(2.8) 2(5.6) pregnancy type wanted 254(38.5) 187(28.4) 52(7.9) 40(6.1) 26(3.9) 27(4.1) 73(11.1) unwanted 34(37.0) 25(27.2) 13(14.1) 7(7.6) 3(3.3) 5(5.4) 5(5.4) table 3: results of multivariate logistic regression analysis risk factors odd ratio (95%ci) p value residency in ahvaz city 0.133 (0.070.22) < 0.001 age ≥ 24 month 1.01 (1.00 1.02) < 0.001 mother’s illiteracy 2.09 (1.20 3.40) 0.005 private housing 3.19 (2.20 460) < 0.001 first child 2.0 (1.28 3.12) < 0.001 ci: confidence interval. 4. discussion: according to the findings of this study, 30.7% of the studied children were injured at least once since birth. age ≥ 24 months, being the first child, living in a private house, being a resident of ahvaz city, and having an illiterate mother were found to be risk factors of home injury among under 5 year old children. burning, falling, poisoning, swallowing objects, choking, and biting were the main home injury mechanisms and the prevalence of home injuries did not vary by gender. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e6 figure 1: area under roc curve for probability of having unintentional home injury in children under 5 years. children under five years old are at higher risk of home injuries as they spend more time at home compared to older children, and are unable to manage potential hazards due to their physical development stage. other studies have also shown high prevalence of non-fatal injuries among children under 5 (10). in line with our study, qiu et al. and arif et al. also reported that children over 24 months old had a higher risk of home injury (11, 12). regarding mechanism of injury, our results are in line with other studies that have reported burning, falling and poisoning as the most common mechanisms among preschool children (9, 11, 13). no gender differences were detected regarding injury risk, which is in line with arif study (12). however, according to the national child development study, there is about two folds raise in risk for boys (14). in contrast, chan et al. showed that female gender is associated with higher risk of home injuries (15). children living in private houses were more at risk for injury, which might be due to the lifestyle in khuzestan province particularly in cities such as ramshir, baghmalek and shoush, khoramshahr. a study reported that need for home repair correlated with injury risk (16). since apartments are more recently built, this might be the reason that children living in private houses are at higher risk of injury. in this study, mother’s illiteracy and being the first child were risk factors of home injury. both might be due to the fact that illiterate mothers and first time mothers have less information regarding handling and taking care of a child. in line with the results of this study, a study in egypt also showed that birth order is a risk factors of home injury. in contrast, addor et al. reported that birth order did not affect injury risk and halawa et al. reported that 2nd and 3rd born children are at higher risk of injury (17, 18). in addition, regarding mother’s illiteracy they reported that children of highly educated mothers are at higher risk of injury (17). in line with the results of this study, kamal reported that children of less educated parents were at higher risk for injury (19). higher frequency of non-fatal home injuries was detected among children of some specific ethnicity with low level of socio-economic living standard, low quality of housing, and low level of mother education level. pregnancy type also strongly correlated with injuries and affected mother’s attitude to protecting and taking care of the children; reported also in other investigations(11, 20). in fact, there family socio-economical and maternal parenting and supervision level also have been addressed as determinants of non-fatal children injury occurrence (20, 21); challenging living conditions, lack of safe place to play as well as child care giver absence put children at the risk of injury (22). being a resident of ahvaz city was also a risk factor for unintentional injuries. this is not consistent with the results of a meta-analysis that reported in canada and the us rural children are more at risk for injuries (23). from injury prevention perspective, this study implies that the risk of non-fatal injury in children under 5 years old is a complex and multi-dimensional and successful prevention strategies setting require to target multiple components. efforts to reduce the risk of home injury require a risk estimation tool to predict non-fatal home injuries. high risk families for child home injury occurrence should be identified by heath care providers through screening tools to help parents to classify their risky offspring. health care providers or parents or both should develop different strategic teaching systems to effectively enhance children’s understanding of the safety issue in order to reduce children’s risk of hazard (24). we suggest further investigations to uncover more potential mechanisms and home causality predictors, which may enable classifying risky children more accurately. limitations this study had some limitations. since the mother was asked about data regarding former injuries she might have either forgotten or lied about the child’s history to avoid being labeled as irresponsible. in addition, more attention to data collection to have balanced subgroups and evaluating more variables, such as attendance of another person at the time of injury occurrence, could improve level of model sensitivity. in addition, further research on home injury risk estimation in grades and scores are needed; this propose might define and estimate risk score more precisely rather than only a risky class. application and comparison different intelligent modeling methods such as machine learning approaches as has been applied in other areas can be used both for more accurate models development and risk estimation purpose(25). these models have the potentiality of being replaced by current system that consider all children this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. nouhjah et al. 6 in same level of risk and provide the unique intervention for all children. 5. conclusion: according to the findings of this study, 30.7% of the studied children were injured at least once since birth. burning, falling, poisoning, swallowing objects, choking, and biting were the main home injury mechanisms. age ≥ 24 months, being the first child, living in a private house, being a resident of ahvaz city, and having an illiterate mother were found to be risk factors of home injury. 6. appendix 6.1. acknowledgements special thanks go to social determinants of health research center, deputy of research development, public health students and health staff at health centers of khuzestan province under the coverage of the ahvaz jundishapur university of medical sciences for their kind attention and great cooperation. 6.2. conflict of interest the authors declare that they do not have any conflict of interest. 6.3. funding support this research was funded by the social determinants of health research center at ahvaz jundishapur university of medical sciences (research id: h2213-a). 6.4. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. harvey a, 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from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references emergency. 2017; 5 (1): e21 or i g i n a l re s e a rc h predictive factors of poor outcome in road traffic injures; a retrospective cohort study hamid reza hatamabadi1, majid shojaee2, parvin kashani2, mohammad mehdi forouzanfar2, dorrin aghajani nargesi2, mohammad reza amini esfahani3 ∗ 1. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, shiraz university of medical sciences, shiraz, iran. received: june 2016; accepted: august 2016; published online: 9 january 2017 abstract: introduction: road traffic injuries (rti) are among the most important health problems worldwide as they cause more than 1.2 million deaths and 50 million injuries each year. the present study aims to evaluate the outcome and aftermath of rti in those who were injured and hospitalized due to traffic accidents. methods: in the present retrospective cohort study with a one-year follow-up, data were extracted from the profiles of the rti hospitalized patients. outcome of the patients was evaluated at the time of discharge and 1-year later including their living state, presence of a disability or complete recovery. results: 1471 patients were studied (mean age of 32.8±17.0; 80.3% male). 571 (38.8%) had mild disability, 684 (46.5%) moderate disability, and 85 (5.8%) had severe disability at the time of discharge. in the end, 53 (3.6%) died. in the 1-year follow-up, 194 (13.2%) had mild disability, 43 (2.9%) had moderate disability, 9 (0.6%) had severe disability, and 7 (0.5%) were in a vegetative state. presence of an underlying disease (p=0.03), loss of consciousness for more than 24 hours (p=0.04), spinal injury (p=0.002), presence of multiple trauma (p=0.01), increased iss (p<0.001), need for ventilator (p<0.001), and organ injuries during hospitalization (p<0.001) are independent factors that increase the risk of poor outcome in rti patients. conclusion: based on the results of the present study, underlying illnesses, loss of consciousness for more than 24 hours, spinal injury, multiple trauma, increased iss, need for ventilator, and organ injuries during hospitalization were independent factors that increased the probability of poor outcome in rti injuries. keywords: accidents, traffic; hospitalization; patient outcome assessment; epidemiology © copyright (2017) shahid beheshti university of medical sciences cite this article as: hatamabadi h, shojaee m, kashani p, forouzanfar m, aghajani nargesi d, amini esfahani m. predictive factors of poor outcome in road traffic injures; a retrospective cohort study. emergency. 2017; 5 (1): e21. 1. introduction road traffic injuries (rti) are among the most important health problems worldwide as they cause more than 1.2 million deaths and 50 million injuries each year. more than 90% of mortalities due to rti occur in low and middle income countries (1, 2). it is predicted that in the next 5 years rti will lead to 6 million deaths and 60 million injuries, only in developing countries. in 1990, rti ranked 9t h in the most important factors determining population health and it is pre∗corresponding author: mohammad reza amini esfahani; namazi hospital; namazi square; shiraz university of medical sciences, shiraz, iran. tel: +989171529761; e-mail: dr.amini94@yahoo.com dicted to become the 3r d cause of mortality and disability by 2020. the reports also show that 50% of the dead were 15-43 years old, who are the most effective population in a society’s financial development (3). in iran rti rate is very high and fatal rti rate is 33 in 100000 people, which emphasizes the need for more research and taking preventive measures and efficient treatment in managing rti (4-6). the high social and financial costs of rti and its physical and mental aftermaths on people and societies are the major problem that transportation managers and health providers must face. this challenge is many times more in developing countries, where rti rate is increasing and its direct and indirect costs are more than the developed countries. world bank report shows that the number of people who die of rti in iran has increased by 10%, which is higher than most developing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. hatamabadi et al. 2 panel 1: glasgow outcome scale database search terms 1. death severe injury or death without recovery of consciousness 2. persistent vegetative state severe damage with prolonged state of unresponsiveness and a lack of higher mental functions 3. severe disability severe injury with permanent need for help with daily living 4. moderate disability no need for assistance in everyday life, employment is possible but may require special equipment. 5. mild disability light damage with minor neurological and psychological deficits. 6. good recovery resumption of normal activities, however there may be minor neurological or psychological deficits. countries and is very undesirable and worrisome compared to world standards (2). in its last report, world health organization has expressed the need for more research on the epidemiologic pattern of rti in low and middle income countries to determine the dimensions of the problem and identify those who are most susceptible to rti, since no accurate estimation exists regarding the social and economic effects of rti in these countries. although valuable efforts have been made to identify the effects and outcomes of rti in iran in recent years, there is still a shortage of available data in this regard (7-9). therefore, the present study aims to retrospectively evaluate the outcome and aftermath of rti in those who were injured and hospitalized due to a traffic accident. 2. methods 2.1. study design the present study is a retrospective cohort one, with a oneyear follow-up, carried out in two educational hospitals in tehran, iran. patients referred to the hospitals from april 2012 to march 2013 were included and ethics committee of shahid beheshti university of medical sciences approved the study. data collection forms were anonymous and patient data remained confidential. 2.2. participants the studied population consisted of all the patients injured in rti during the course of the study, who had an accident with at least 1 vehicle. patients with incomplete or unreachable data were excluded. there was no age and sex limitation. 2.3. data collection data collection was done using a checklist that consisted of demographic data (age, sex, level of education), trauma mechanism, type and location of injury, type of vehicle in accident, route of transportation to emergency department (ed) (by ambulance, taxi, or personal vehicle), pre-hospital clinical measures taken, hospitalization status, hospitalization duration, intensive care unit admission, injury severity score (iss), need for ventilator, organ failure, and outcome (death, disability, or complete recovery at the time and one year after discharge). data were gathered by trained emergency medicine residents. their trainings consisted of research tool management (how to fill a checklist, data recording) and summarizing medical data. data were extracted from the patients’ profiles and quality of data collection was evaluated by the head researcher of each hospital every 24 hours. in addition, at the end of each week, some checklists were randomly chosen and their quality was controlled by the chief researcher to ensure the quality of data collection. in this study, injury severity was classified into 4 groups: mild (iss < 9), moderate (iss 9-15), severe (iss 16-25), and profound (iss > 25). 2.4. outcomes living status (dead or alive), and disability or complete recovery at the time of discharge were appraised, and in-hospital complications such as embolism, deep vein thrombosis, infection, organ failure, need for ventilator, infection, high or low blood pressure, hypothermia, hypoxia, seizure, sepsis and shock were evaluated. death and severe disability were considered as poor outcome. glasgow outcome scale (gos) was used for the 1-year follow-up outcome evaluation (panel 1). gos divides patients into 2 groups based on desirable and undesirable outcome: poor consisting of gos score 1-3 and desirable with the score of 4-6. in the 1-year follow-up, the patients or their relatives were contacted by phone. cases that could not be contacted after calling 3 times (due to not responding, wrong number or the phone number being sold) were considered as loss to follow-up. 2.5. statistical analyses data were analyzed using stata 11.0. quantitative data were reported as mean and standard deviation, and qualitative ones as frequency and percentage. outcome (death, disability, complete recovery) and complications were assessed based on demographic data, baseline characteristics and clinical information. the association of each variable with 1-year outcome was then determined using independent t-test, chi square and exact fisher’s test. finally, to assess the independent predictive factors of patient outcome, stepwise multivariate logistic regression analysis was used. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e21 table 1: relationship between demographic data and baseline characteristics of patients and their 1-year outcome factors desirable outcome poor outcome total p age(mean ± sd) 32.0 ± 16.5 40.0 ± 21.5 32.8 ± 17.0 < 0.001 sex(n, %) male 1126 (80.3) 55 (79.7) 1181 (80.3) 0.90 female 276 (19.7) 14 (20.3) 290 (19.7) reference by(n, %) ambulance 1003 (71.5) 45 (65.2) 1048 (71.2) 0.001 personal vehicle 199 (14.2) 4 (5.8) 203 (13.8) referral from another hospital 200 (14.3) 20 (29.0) 220 (15.0) time before arrival (mean ± sd) 32.9 ± 20.3 33.5 ± 16.0 33.1 0.85 trauma mechanism(n, %) automobile 1024 (73.0) 39 (56.5) 1063 (72.3) 0.03 motorcycle 153 (10.9) 11 (16.0) 154 (10.5) collision with a stationary object 187 (13.3) 16 (23.2) 203 (13.8) bicycle 2 (0.1) 0 (0.0) 12 (0.7) unknown 36 (2.6) 3 (4.3) 39 (2.7) history of illness(n, %) no 1263 (90.1) 0 (0.0) 1263 (85.9) diabetes 41 (3.0) 4 (5.8) 45 (3.1) 0.11 high blood pressure 59 (4.1) 58 (84.1) 117 (7.9) 0.11 ischemic heart disease or stroke 37 (2.7) 4 (5.8) 41 (2.8) 0.08 myocardial infarction 2 (0.1) 2 (2.9) 4 (0.3) 0.009 cerebrovascular accident 0 (0.0) 1 (1.4) 1 (0.1) 0.04 history of drug use(n, %) no 1278 (90.9) 49 (71.0) 1327 (90.2) < 0.001 yes 127 (9.1) 20 (29.0) 144 (9.8) drug abuse(n, %) no 1134 (80.9) 53 (76.8) 1187 (80.7) 0.43 cigarette 129 (9.3) 9 (14.8) 138 (9.4) 0.16 alcohol 23 (1.7) 0 (0.0) 23 (1.6) 0.62 drugs 103 (7.4) 6 (9.8) 109 (7.4) 0.49 hookah 3 (0.2) 0 (0.0) 3 (0.2) 0.72 psychotropic drugs 10 (0.7) 0 (0.0) 10 (0.7) 0.99 in all analyses, p < 0.05 was considered as significance level. 3. results: 3.1. baseline characteristics of the patients 1941 patients were included in this study, 206 (10.6%) of which were discharged against medical advice and there were 264 (15.2%) cases of loss to 1-year follow-up. therefore no data was available regarding their outcome. analyses were done on the remaining 1471 patients. their mean age was 32.8 ± 17.0 years ranging from 1 to 91 years (80.3% male). tables 1 and 2 show the patients’ demographic data, baseline characteristics and patients’ clinical variables. the 18-29 years age group had the most frequency with 657 (37.9%) patients. most of the patients (71.2%) were referred to the hospital by an ambulance. trauma mechanism was car accident in 1063 (72.3%) patients. urban areas were the most common location with 43.5%. glasgow coma scale (gcs) was between 14 and 15 in 1372 (93.3%) of the patients, 9-13 in 57 (3.9%), and < 9 in 42 (2.8%) cases. this loss of consciousness lasted less than 6 hours in 54 (3.9%), 6-24 hours in 1 (0.1%) and more than 24 hours in 16 (1.1%) patients. lower extremities injury (53.4%) was the most common injury. 3.2. patient outcomes mean length of stay was 8.7 ± 8.3 days ranging from 1 to 96 days. 38 (2.6%) patients were hospitalized in the intensive care unit (icu). mean hospitalization duration in icu was 7.7 ± 9.1 days (ranged 1-52 days). 17 (1.2%) of the patients were affected with wound infection, 6 (0.4%) with pulmonary embolism 8 (0.6%) with fat embolism, and 2 (0.2%) had deep vein thrombosis. in evaluating in-hospital organ failure, 6 (0.4%) cases of respiratory diseases, 6 (0.4%) cases of coagulation abnormalities, 1 (0.1) patient with liver problem, 8 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. hatamabadi et al. 4 table 2: relationship between clinical factors of patients and their 1-year outcome factor desirable outcome poor outcome total p life-threatening signs on admission(n, %) no 1286 (91.7) 65 (94.2) 1351 (91.8) 0.43 airway obstruction 10 (0.7) 0 (0.0) 10 (0.7) 0.99 respiratory problems 35 (2.5) 0 (0.0) 35 (2.4) 0.41 circulation problems 71 (5.1) 4 (6.8) 75 (5.1) 0.99 pupil(n, %) normal 1120 (98.9) 51 (96.2) 1171 (98.7) 0.22 single-sided pupil dilation 8 (0.7) 1 (1.9) 9 (0.8) double-sided mydriasis pupil dilation 5 (0.4) 1 (1.9) 6 (0.5) glasgow coma scale(n, %) 14-15 1309 (93.4) 63 (91.3) 1372 (93.3) 0.34 9-13 55 (3.9) 2 (2.9) 57 (3.9) > 9 38 (2.7) 4 (5.8) 42 (2.8) head trauma(n, %) no 1085 (77.4) 39 (54.5) 1124 (76.4) < 0.001 yes 317 (22.6) 30 (43.5) 347 (23.6) loss of consciousness duration(n, %) no 1274 (95.5) 47 (81.0) 1321 (94.9) < 0.001 < 6 hours 53 (4.0) 1 (1.7) 54 (3.9) 6-24 hours 1 (0.1) 0 (0.0) 1 (0.1) > 24 hours 6 (0.4) 10 (17.3) 16 (1.1) amnesia(n, %) no 1218 (92.4) 47 (83.0) 1265 (91.9) < 0.001 < 6 hours 92 (7.0) 3 (5.2) 95 (6.9) 6-24 hours 2 (0.2) 0 (0.0) 2 (0.2) >24 hours 6 (0.4) 8 (13.8) 14 (1.0) site of injury(n, %) neck 56 (4.0) 5 (7.2) 61 (4.4) 0.1 face 16 (1.1) 0 (0.0) 16 (1.1) 0.99 chest 111 (7.9) 12 (17.4) 123 (8.8) < 0.001 abdomen and hip 112 (8.0) 12 (17.4) 124 (8.9) < 0.001 spine 61 (4.4) 10 (14.5) 71 (5.1) < 0.001 upper extremities 247 (17.6) 8 (11.6) 255 (18.3) 0.20 lower extremities 724 (51.6) 22 (31.9) 746 (53.4) 0.001 multiple trauma(n, %) no 1180 (84.2) 40 (58.0) 1220 (82.9) < 0.001 yes 222 (15.8) 29 (42.0) 251 (17.1) injury severity score(n, %) < 9 (mild) 628 (52.4) 3 (4.5) 631 (49.9) < 0.001 9-15 (moderate) 338 (28.2) 5 (7.6) 343 (27.1) 16-25 (severe) 160 (13.4) 24 (36.4) 184 (14.6) > 25 (profound) 72 (6.0) 34 (51.5) 106 (8.4) (0.6%) patients with cardiovascular diseases, 8 (0.6%) with kidney diseases, and 5 (0.3%) with sepsis were observed (figure 1a-b and table 3). out of the 1471 studied patients, 312 (21.2%) were discharged with full recovery, while 571 (38.8%) had mild disability, 684 (46.5%) had moderate disability, and 85 (5.8%) had severe disability at the time of discharge. in the end, 53 (3.6%) patients died (figure 1c). after 1 year, 1165 (79.2%) patients had fully recovered, 194 (13.2%) had mild disability, 43 (2.9%) had moderate disability, 9 (0.6%) had severe disability, and 7 (0.5%) were in a vegetative state. no cases of death were reported during this time (figure 1d). 4. predictive factors of 1-year outcome: 4.1. univariate analyses higher ages (p < 0.001); being referred from another hospital (p = 0.001); high energy trauma mechanism (p = 0.03); having a history of myocardial infarction (p = 0.009), cerebral vascuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e21 table 3: relationship of therapeutic measures and side effects during hospitalization with patients’ 1-year outcome variable* desirable outcome poor outcome total p prehospital emergency measures(n, %) serum therapy 1037 (74.5) 50 (72.5) 1087 (73.9) 0.71 intubation 1 (0.06) 0 (0.0) 1 (0.1) 0.99 oxygen therapy 765 (55.0) 46 (66.7) 811 (55.1) 0.06 neck collar 443 (31.9) 33 (47.8) 476 (32.4) 0.006 back board 326 (23.5) 31 (44.9) 357 (28.2) < 0.001 splinting 571 (41.1) 26 (37.7) 597 (40.6) 0.57 inhospital emergency measures(n, %) blood transfusion 149 (10.6) 40 (57.0) 189 (12.8) < 0.001 cardiopulmonary resuscitation 2 (0.14) 51 (73.9) 53 (3.6) < 0.001 chest tube 50 (3.6) 19 (27.5) 69 (4.7) < 0.001 diagnostic peritoneal lavage 19 (1.4) 23 (33.3) 42 (2.8) < 0.001 need for ventilator 48 (3.4) 50 (77.5) 98 (6.7) < 0.001 organ injury(n, %) no 1355 (96.5) 35 (50.1) 1390 (94.5) < 0.001 respiratory 1 (0.07) 5 (7.4) 6 (0.4) < 0.001 coagulation abnormality 1 (0.07) 5 (7.4) 6 (0.4) < 0.001 liver 0 (0.0) 1 (1.5) 1 (0.1) 0.05 cardiovascular 2 (0.1) 6 (8.8) 8 (0.6) < 0.001 kidney 4 (0.3) 4 (5.9) 8 (0.6) < 0.001 sepsis 1 (0.07) 4 (5.9) 5 (0.3) < 0.001 infection 26 (1.9) 8 (11.6) 34 (2.3) < 0.001 embolism 10 (0.7) 1 (1.5) 11 (7.5) 0.41 deep vein thrombosis 2 (0.1) 0 (0.0) 2 (0.2) 0.99 *, some patients have more than one injury or underwent more than one procedure. table 4: independent effective factors on 1-year outcome of rti patients variable regression coefficient 95% confidence interval p underlying illness 1.15 0.11 – 2.34 0.03 loss of consciousness > 24 hours 0.62 0.02 – 1.22 0.04 abdominal trauma -2.62 -4.49– -0.74 0.006 spinal trauma 1.98 0.75 – 3.21 0.002 multiple trauma 1.02 0.10 – 2.14 0.01 increased injury severity score 0.17 0.10 – 0.25 < 0.001 intensive care unit hospitalization 1.98 -3.81 – 0.19 0.03 need for ventilator 3.22 2.0 – 4.45 < 0.001 organ injuries during hospitalization 3.69 2.16 – 5.21 < 0.001 lar accident (p = 0.04), drug use (p < 0.001); using neck collar (p = 0.006) and back board (p < 0.001) at pre-hospital setting; having head trauma (p< 0.001); the longer duration of loss of consciousness (p <0.001); need for ventilator (p < 0.001); hospitalization in icu (p < 0.001); and higher iss (p < 0.001) were the factors that had a significant association with patient outcome (table 1-3). 4.2. multivariate analyses presence of an underlying illness (p = 0.03), loss of consciousness for more than 24 hours (p = 0.04), spinal injury (p = 0.002), presence of multiple trauma (p = 0.01), increased iss (p < 0.001), need for ventilator (p < 0.001), and organ failure during hospitalization (p < 0.001) were independent factors that increased the risk of poor outcome in rti patients. in contrast, a single abdominal trauma (p = 0.006) and hospitalization in icu were associated with improved outcome (table 4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. hatamabadi et al. 6 figure 1: patient outcomes. a) in-hospital complication; b) organ injuries during hospitalization; c) outcome of the patients at the time of discharge; d) 1-year outcome of the patients. 5. discussion: the present study showed that young males are most frequently affected with rti and motorcycle is the most important cause, which is in line with previous studies. for instance, yousefzadeh et al. showed that the number of men involved in rti was 3.6 times the women, and about 50% of the patients were 20-44 years old. most injuries were due to motorcycle accidents and 5.2% died in the end (10). torabi et al. also revealed that 89.9% of the injured were male and mostly (56.8%) 16-25 years old (11). in another cross-sectional study in tehran, most of those injured in rti were 21-30 years old (22.3%), and mainly pedestrians (54.6%) (12). hatamabadi et al. also expressed that majority of those who were killed in traffic accidents were male, most of which were 2140 years old and uneducated (13). these researchers, in another study, reported 7.0% mortality rate due to rti. 78.5% male and the majority aged 20-30 years old and most used personal cars (52.9%) (14). this higher mortality rate was due to the nature of the road they studied. abali-tehran is an inter-city road in iran that has steep slopes and can be very slippery especially in rainy seasons. in addition, driving speed is much higher compared to urban streets and there are fewer motorcycles, which might justify the low rate of motorcycle accidents. in the present study, mortality due to rti was 3.05%. akbari et al. studied rti in 10 provinces of iran and concluded that mortality rate in unintentional accidents was 4% which is in line with this study. traffic accidents with 7.51% were the most frequent cause of death (15). in addition, yousefzadeh et al. epidemiologically evaluated effective factors in trauma patients in rasht, iran, and showed that 5.17% of rti injuries result in death (10). torabi et al. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e21 assessed motorcycle accidents and revealed 4% mortality in these patients. their most important cause of death being head and neck trauma (11). a study by kadivar et al. also showed that rti was the major cause of death in unintentional accidents (16). despite rti being the third most important cause of death, since it targets the younger population (mean age was about 34 years in 2001), it ranks first in the list of causes for years of potential life lost (6, 17). controlling and decreasing rti is not the responsibility of health care providers but informing the responsible organizations on the importance of this problem and cooperating with them to control and reduce this major cause of death can be. the statistics of this study reveal the necessity of paying more attention to emergency services and providing trauma centers and equipping them. the reason for high mortality rate of rti and its increase might be industrialization and broader usage of motor vehicles in recent years without improving standards for this new way of life. reducing drug abuse, safety education, improving protective measures in working environment, rapid first aid in the location of accident, eliminating causing factors (reducing speed, putting appropriate signs on the road, etc), enforcing more restricted traffic rules, and providing rehabilitation services are among the useful measures, which can aid in prevention of accidents and therefore decrease mortality. the findings of logistic regression analysis showed that presence of an underlying illness, loss of consciousness for more than 24 hours, spinal injury, presence of multiple trauma, increased iss, need for ventilator, and organ injuries during hospitalization were independent factors that increased the risk of poor outcome in rti patients, while a single abdominal trauma and hospitalization in icu led to improved final outcome. these results emphasize the importance of careful evaluation of these patients in ed, so that no injury goes unnoticed, because if the injuries are rapidly diagnosed and properly treated outcome can improve (18, 19). this is confirmed by the result of this study that states hospitalization in icu leads to improved outcome. therefore, paying attention to these patients and maintaining proper tissue perfusion during hospitalization can prevent organ disabilities and therefore poor outcome. 6. conclusion: based on the results of present study, underlying illnesses, loss of consciousness for more than 24 hours, spinal injury, multiple trauma, increased iss, need for ventilator, and organ injuries during hospitalization were independent factors that increased the probability of poor outcome in rti injuries. 7. appendix 7.1. acknowledgements this research has been supported by shahid beheshti university of medical sciences & health services. 7.2. authors contribution all authors passed the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none declared. references 1. toroyan t. global status report on road safety: time for action2009. 2. peden m, scurfield r, sleet d, et al. world report on road traffic injury prevention. world health organization geneva; 2004. 3. organization wh. world health statistics 2009: world health organization; 2009. 4. saadat s, soori h. epidemiology of traffic injuries and motor vehicles utilization in the capital of iran: a population based study. bmc public health. 2011;11(1):488. 5. ghaffar a, hyder aa, masud ti. the burden of road traffic injuries in developing countries: the 1st national injury survey of pakistan. public health. 2004;118(3):211-7. 6. saadat s, yousefifard m, asady h, jafari am, fayaz m, 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eastern mediterranean health journal. 2006;12(3/4):382. 16. kadivar m, aramesh k, sharifi b, asad a. the prevalent causes of mortality in fars province, 2001. med j hormozgan uni. 2006;10(1):47-55. 17. gururaj g, uthkarsh ps, rao gn, jayaram an, panduranganath v. burden, pattern and outcomes of road traffic injuries in a rural district of india. international journal of injury control and safety promotion. 2014 (ahead-ofprint):1-8. 18. chini f, farchi s, camilloni l, giarrizzo ml, giorgi rossi p. health care costs and functional outcomes of road traffic injuries in the lazio region of italy. international journal of injury control and safety promotion. 2014 (aheadof-print):1-10. 19. arhami doulatabadi a, hedari k, hatamabadi hr, vafaei a. frequency of lower limb injuries and their causes among motorcycle accident admitted into imam hussein hospital during one year. j saf promot injury prev. 2013;1(1):26-31. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: predictive factors of 1-year outcome: discussion: conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e43 or i g i n a l re s e a rc h comparing the severity of injury and trauma pattern between scooter and street motorcycle riders; a prospective cohort study mansour bahardoust1, arman karimi behnagh2, abolfazl bagherifard1, mehrdad khodabandeh3, sayed ali emami3, shakiba ghasemi assl2, farid najd mazhar1∗ 1. bone and joint reconstruction research center, shafa orthopedic hospital, iran university of medical sciences, tehran, iran. 2. faculty of medicine, iran university of medical sciences, tehran, iran. 3. neuromusculoskeletal research center, department of physical medicine and rehabilitation, iran university of medical sciences. received: april 2021; accepted: may 2021; published online: 8 june 2021 abstract: introduction: the popularity of motorcycle riding in iran is increasing. however, there is a lack of information about the safety of different motorcycle types. this study aimed to compare the severity of injury and trauma pattern between scooter (vespa) and street (standard) motorcycle riders. methods: in a prospective cohort study, a comparison of demographics, injury severity, trauma pattern, and clinical characteristics between 324 riders (162 vespa and 162 standard motorcycles) admitted to emergency departments was undertaken. the risk factors associated with severe injuries in the two groups were also determined. an emergency medicine specialist determined the severity of trauma based on the abbreviated injury scale (ais). results: the odds ratio (or) of severe injuries was significantly higher in the standard motorcycle riders’ group (or: 3.09; 95% ci: 1.94.21; p: 0.013). the frequency of lower extremity fractures was significantly lower in the vespa group (or: 4.11; 95% ci: 2.01-6.25; p = 0.012). the frequency of admission to the intensive care unit was significantly higher in the standard motorbike riders’ group (or: 1.64; 95% ci: 1.11-2.51; p = 0.033). the multivariate analysis indicated that motorcycle type, the speed at the time of the accident, use of helmet, and age of riders are the most important predictors of trauma severity in riders (p<0.05). conclusion: the pattern of injury varies between standard and vespa motorcycles. the standard motorcycle riders were prone to a higher risk of adverse outcomes such as severe injuries. due to the particular structure of scooters, the rate of lower limb injuries was significantly lower than standard motorcycles. keywords: wounds and injuries; emergency treatment; accidents, traffic; motorcycles; mortality cite this article as: bahardoust m, karimi behnagh a, bagherifard a, khodabandeh m, emami s a, ghasemi assl s, najd mazhar f. comparing the severity of injury and trauma pattern between scooter and street motorcycle riders; a prospective cohort study. arch acad emerg med. 2021; 9(1): e43. https://doi.org/10.22037/aaem.v9i1.1229. 1. introduction trauma is regarded as one of the major causes of death in developed countries, ranking high on the list of mortality and morbidity causes in younger populations. traffic injuries are the leading cause of death in children and young adults (ages 5-29). although ranked as the sixth major global mortality cause, it is predicted that fatality of traffic injuries ∗corresponding author: farid najd mazhar; bone and joint reconstruction research center, shafa orthopedic hospital, iran university of medical sciences, tehran, iran. tel/fax: +98 21 33542041, email: najdmazhar.f@iums.ac.ir, orcid: https://orcid.org/0000-0001-8496-9852. will increase and it will rise to the fourth spot (1). more than half of all road traffic deaths occur in vulnerable road users: pedestrians, cyclists, and motorcyclists (2). injuries sustained in two-wheeled vehicle accidents are often more severe than those sustained in automobile accidents (3). besides, globally, the probability of motorcycle riders being injured is about three times more than car occupants and they are sixteen times more probable to die due to road traffic injuries (4). lowand middle-income countries are disproportionately more burdened by the significant mortality and morbidity inflicted by motor-vehicular accidents (mva) (5, 6). the most common causes of motorbike-related mva’s are illegal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. bahardoust et al. 2 overtaking, excessive speeding, alcohol intoxication and substance abuse, motorbike type and safety, and not wearing standard protective gear such as helmets (7, 8). in iran, motorbikes are widely used, resulting in an increased frequency of motorbike-related mvas that impose a high burden of disease on the healthcare system (5, 6, 9). the mva-associated mortality in motorcyclists, mainly occurs due to head traumas and helmets can reduce the regarded rate (10). moreover, musculoskeletal injuries are common among motorized two-wheeled vehicle riders, and they are frequently associated with head and neck injuries. the lower extremities are the most common sites of orthopaedic injuries in a motorcycle collision. the incidence in some studies ranges between 40% and 60%, and limb entrapment is regarded as the most common mechanism of injury (11). the range and variety of motorcycle models continue to grow. however, in this study, we focused on two types, standard and common street-legal motorcycle types and vespa scooter (figure 1). scooters are primarily designed for use at low and medium speeds on urban streets. relatively small in size with small-diameter wheels, their step-through design and general appearance differ significantly from full-sized motorcycles (12). vespa scooters are designed with a particular guard for the legs. moreover, compared to standard motorcycles, vespa scooters, have lower speed, smaller engine capacities, and also smaller wheel with high manoeuvre capability, which provide an advantage of better safety profile. the number of studies tackling the differences in mvarelated trauma based on motorbike type is somewhat limited. however, few reports have documented less severe traumas in vespa motorbikes compared to others. the current literature is mainly focused on the fatality of different motorcycle types and the coverage of other aspect of motorcyclerelated collisions is limited. this prospective study aimed to compare the fatality and orthopaedic injury rates between vespa motorbikes and other conventional street-legal motorbikes. 2. methods 2.1. study settings and design this prospective cohort study enrolled 324 motorbike riders involved in an intra-city motor-vehicular accident resulting in upper and lower limb fracture(s) admitted to the emergency departments (eds) of hospitals affiliated to iran university of medical sciences, tehran, iran, between may 2019 and may 2020. after assessing eligibility criteria, the patients were divided into two groups, based on the type of motorbike involved: the first group (n=162) comprised of vespariders, while the second group (n=162) were riding standard motorbikes. to gain access to their medical records, patients were asked to fill out a written informed consent form. the study protocol was approved by ethics committee of iran university of medical sciences (ethics code: ir.iums.rec.1398.288). 2.2. study population patients were enrolled through cluster sampling of eds and during the study recruitment period all the patients with following criteria were recruited for this study: 1) involvement in an mva while riding a vespa or standard motorbike; 2) admission to ed; 3) availability of complete accident reports; 4) availability of complete motorbike documentation; 5) age between 18-50 years. our exclusion criteria were as follows: 1) incomplete accident report; 2) occurrence of an incident out of the city bounds; 3) admission to eds for reasons other than mva (i.e., falling). the patients were matched for age, intoxication, speed, and engine power to control confounding factors. 2.3. data source and measurements demographic data, age, gender, type of motorbike (scooter or standard), the speed at the time of the incident, intoxication with alcohol or other substances, mechanism of trauma, and status of using safety equipment were gathered using a predesigned checklist. besides clinical and radiologic findings, including fracture location and severity, duration of hospitalization, intensive care unit admission, the cause of death, place of death, and the interval between accident and death were gathered using patients’ records and if possible, a brief interview was done (if they were alive). fracture type and treatment procedures were classified based on the icd10 manual. the trauma mechanism was classified into three groups: driver error, vehicular factors, and environmental causes. the details on the accident-associated parameters, such as type of motorbike, mechanism of accident, and speed of each motorbike at the time of accident were provided by exploring the police reports about the accident scene. an emergency medicine specialist determined the severity of trauma based on the abbreviated injury scale (ais) (13). ais evaluates trauma severity based on the extent of anatomical injuries. in this scaling system, various injuries are exclusively coded, and the overall severity is classified into six groups: mild, moderate, serious, severe, critical, and life-threatening. the data for each group was gathered separately. an orthopaedic surgeon determined the definitive location of the fracture(s) by examining radiologic images (14). 2.4. statistical analysis all the statistical analyses were performed using spss software for windows v22. descriptive analysis was performed and results were reported as mean and median for quantitative data and frequency and regarded percentage for qualitathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e43 tive data in both groups. the kolmogorov smirnov test was used to assess data normality. the t-test and non-parametric mann whitney u tests were used to compare normally distributed and otherwise data. the chi-square test was used to compare quantitative data between the groups. significance was reported using odds ratios (or) and a 95% confidence interval (ci). logistic regression was performed to determine the most important risk factors of the severity of trauma. the p-values <0.05 were deemed statistically significant. 3. results 3.1. baseline characteristics of studied cases this study enrolled a total of 324 motorbike riders (162 scooters and 162 standard motorcycles). the mean age of the study population was 28.01 ± 1.22 years (100% male). table 1 compares the baseline characteristics of the study subjects between scooter and standard riders. the mean age for the vespa and the traditional motorbike group were 27.90 ± 20.30 and 29.03 ± 21.22 years, respectively (p = 0.42). 104 (64.2%) standard and 98 (60.5%) scooters motorbike riders were exceeding 60km/h. no significant differences were observed between the two groups regarding age (p = 0.42), accident speed (p =0.11), helmet use (p = 0.079), the main cause of death (p = 0.28), place of death (p = 0.11), or time of death (p = 0.083). severity of trauma based on ais score was greater in the standard motorbike group (p = 0.001). 3.2. comparing the location of injury and clinical outcomes table 2 compares the location of injury and clinical outcomes between the two groups. the frequency of lower extremity fractures was significantly lower in the scooter group (or: 4.11; ci 95%: 2.01-6.25; p = 0.012). in the standard motorbike group, the most common fracture locations were the knee, the shin, the ankle, and the foot. however, the frequency of these fractures was significantly lower in the scooter group (p=0.001). the two groups were similar regarding trauma to the head and neck (p > 0.081) and other limbs (p > 0.05). the overall mortality (p=0.084) and duration of hospital stay (p=0.76) were similar in the two groups. the frequency of admission to the intensive care unit was significantly higher in the standard motorbike riders’ group (17.9% versus 9.9%; p = 0.033). 3.3. risk factors of severe and critical trauma in general, the trauma was severe or critical in 100 (30.9%) of riders, based on the ais. we used adjusted logistic regression analysis to control confounders in evaluation of factors associated with severe trauma. all variables with statistical significance in univariate analysis were included in logistic regression. the multivariate analysis indicated that age < 24 years (odds: 2.53; 95%ci: 1.46 – 3.66; p = 0.012), accident speed ≥ 60 km/hours (odds: 3.56; 95%ci: 2.12 – 5.10; p = 0.001), use of a helmet (odds: 0.66; 95%ci: 0.46 – 0.87; p = 0.001), and standard motorcycle type (odds: 1.47; 95%ci: 1.07 – 1.98; p = 0.018) were among the most important risk factors of trauma severity in this study. 4. discussion this study characterized subnational data on patients admitted to the ed who were involved in standard street-based motorcycles or vespa scooters. our data suggest that vespa scooters possess better safety profile in comparison to motorcycles. although the two groups did not show any difference in terms of mortality rate and duration of hospital stay, the number patients admitted to icu was significantly higher in motorcycle riders, which implies much severe injuries among the motorcyclists. moreover, site analysis of the injuries showed that motorcycle riders experienced a higher frequency of injuries in lower extremities. furthermore, analysis of the factors associated with severity of injuries, revealed that type of vehicle was one of the factors that could affect the severity of the injuries and the riding of standard street-based motorcycles can lead to more severe injuries. the prevalence of using low-speed motorcycles such as scooters has been increasing. this mainly owes to the affordability and low fuel consumption of this type of vehicle (15). previous reports on the safety profile of scooters revealed that this increase in riding this type of vehicle may lead to a higher burden of disease (15, 16). however, these reports mainly focused on low-speed motorcycles. although the higher consumption rate of this type of motorcycle can inflate the regarded burden of disease, studies similar to our work revealed that overall, low-speed motorcycles such as vespa scooters showed better safety profiles (17, 18). the use of either types of motorcycle can be associated with injuries including fractures and internal organ damages. however, the pattern and distribution of injuries showed discrepancy between the two groups. according to our analysis, vespa riders had a higher percentage of injuries to head/neck and upper extremities; however, these observations failed to have statistical significance. on the other hand, motorcycle riders showed considerably more injuries in lower extremities. our findings are inconsistent with the different injury patterns previously described, with the upper extremity more common in motorcycle riders and injury to lower extremities were more common in scooter or moped riders (18, 19). the source of discrepancy can be that the type of scooter and also counting moped and scooter as one group would change the safety profile of the scooters reported in studies. besides, head injuries, with a higher frequency among motorcycle riders, were considered the most this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. bahardoust et al. 4 common cause of death in both groups (18). like upper extremity injuries, the percentage of injury to head and neck was higher in vespa group. an explanation for this observation was provided by white et al. based on their study, scooter riders were less likely to use safety equipment (18). also, the previous reports showed that using safety equipment such as helmets could reduce the risk of death and severe injuries (10). furthermore, in an epidemiologic study in iran, 23% of all fatal traffic injuries belonged to motorcycle riders, among whom 59% of all mortalities were due to head injuries. most motorcycle fatalities belonged to the 1824 years age group (29.1%), and also, the overall percentage of safety helmet use among motorcycle accident victims was estimated at 37.4% (9). in this study, the mortality rate was not different between the two study groups. however, riding a motorcycle can increase the risk of severe injuries. in a comparative study in netherlands (19), it was demonstrated that the vehicle type being light moped was among the factors that increased the risk of severe injuries. interestingly, the speed at the time of accident and death did not differ significantly between the two study groups. although the number of cases who died on the accident scene was higher in the motorcycle group (64.2% vs. 60.5%), this difference was not significant. nonetheless, this finding may imply that the severity of accidents and, consequently, the regarded injury at the time of the accident were considerably higher among motorcycle riders. in another survey by blackman et al. (17), the factors influencing accident severity among motorcycle, moped, and scooter riders were evaluated. our study and other reports showed that riding motorcycles were associated with a higher rate of severe accidents in comparison to scooters. moreover, they reported that one reason for such observation could be the use of each vehicle (17). for instance, scooters are mainly used for short distances and usually at low speed. however, the motorcycle is primarily used in long distances and therefore, used at high speeds. nonetheless, in their study and other surveys including the present study, speed did not play a pivotal role in the severity of injuries or mortality rates (10, 17, 18). there was no significant difference between the two groups regarding high or low speed riding in our study, and the prevalence of above 60 km/h was similar in the two study groups. also, we observed that most of the collisions occurred at the speed range of 50-75 km/h. nevertheless, this can mislead us since this categorization did not indicate the prevalence of very high speed, i.e., above 90 km/h in each group. inconsistent with our observation, blackman et al. (17) showed that speed above 80 km/h is associated with a high risk of a severe accident in motorcycle riders. similarly, the speed limits for mopeds and scooters were 90 km/h and 70 km/h, respectively. there was another factor that affected the severity of the accidents regardless of the vehicle type. younger age was associated with more severe accidents. however, this finding was inconsistent with others reports in the literature, indicating that the older ages, specially above 75 years, is associated with undesirable outcomes among scooter and motorcycle riders (17, 19-21). one possible explanation for this discrepancy can be the fact that all the mentioned studies were conducted in western countries. according to our literature search, in the middle eastern countries, younger age is associated with severe injuries among the motorcycle riders (22). in a comprehensive analysis of motorcycle pattern in iran, it was demonstrated that the majority of motorbike injuries had happened in younger ages. it was demonstrated that the a great deal of young riders did not have any motorcycle riding license making them vulnerable to motorbike-associated injuries (23). 5. strengths and limitations our study had some strengths and weak points. the main strong point of this study was a considerably large number of included participants in each group. besides, this study was designed using a prospective methodology. moreover, unlike the previous reports, the rate of pre-hospital deaths was determined in this study. also, the effect of some confounders such as alcohol intoxication was adjusted in this study, which had not been achieved in studies pursuing similar objectives. the study’s main weakness was that the extraction of several variables such as the mechanism of the accident from police reports limited the classification of injuries based on accident mechanism. also, we failed to follow the patients to understand the post-ed outcomes of the study participants, which could provide insight on the burden of disease provided by each motorcycle type. 6. conclusion this study suggests that riders of vespa scooters and motorcycles may have different patterns of injury. the motorcycles possess a higher risk of severe outcomes, such as higher fatality and severe injuries in comparison to vespa scooters. further evaluation of the injuries sustained by vespa riders is required to understand their impact more fully. 7. declarations 7.1. data availability statement the datasets used and analyzed during the current study are available via the corresponding author on reasonable request. 7.2. acknowledgments hereby, the authors would like to express gratitude to the vice-chancellor for research, iran university of medical scithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e43 ences. 7.3. funding the authors would like to express gratitude to the vicechancellor for research, iran university of medical sciences. 7.4. author contribution all authors meet the standard criteria of authorship contribution based on the recommendations of the international committee of medical journal editor. all authors listed on the title page have read and approved the manuscript, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to " archives of academic emergency medicine" for evaluation and review for possible publishing. 7.5. ethics approval this study was reviewed and approved by the ethics committee of iran university of medical sciences (ir.iums.rec.1398.288), and informed consent was obtained from participants before their inclusion in the study. 7.6. conflict of interest the authors have no conflicts of interest to declare for this study references 1. collaborators gbdcod. global, regional, and national age-sex-specific 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clinical medicine. 2015;3(3):14956. figure 1: scooter (vespa) versus standard (street) type of motorcycles. figure 2: prevalence of traumatic injuries in scooter (vespa) and standard (street) motorcycle riders. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e43 table 1: comparing the baseline characteristics of studied participants between scooter (vespa) and standard (street) motorcycle riders variable motorcycle type p standard (n:162) scooter (n:162) age ( year) mean ± sd 29.03 ± 21.22 27.90 ± 20.30 0.56 16-24 69 (42.6) 76 (46.9) 25-39 59 (36.4) 58 (35.8) 0.42 ≥40 34 (21.0) 28 (17.3) the speed at the time of the accident (km/h) <60 58 (35.8) 64 (39.5) 0.11 ≥60 104 (64.2) 98 (60.5) helmet use yes 101 (62.4) 92 (56.7) 0.079 helmet use in dead riders yes 4/18 (22.2) 4/16 (25.0) 0.062 the direct cause of death head and neck injury 13/18 (72.2) 12/16 (75.0) 0.28 multiple injuries 5/18 (27.8) 4/16 (25.0) death place on the scene of accident 11/18 (61.1) 8/16 (50.0) on the way 2/18 (11.1) 2/16 (12.5) 0.11 in a health facility 5/18 (27.8) 6/16 (37.5) time to death (hours) < 24 12/18 (61.1) 10/16 (62.5) 0.83 ≥ 24 6/18 (39.9) 6/16 (37.5) blood alcohol positive 11 (6.8) 9 (5.6) 0.89 addiction history yes 15 (9.3) 14 (8.5) 0.19 trauma severity* minor 44 (27.2) 64 (39.5) 0.035 moderate 50 (30.9) 66 (40.8) 0.08 serious 40 (24.7) 18 (11.1) 0.013 severe 28 (17.2) 14 (8.6) 0.001 data are presented as mean ± standard deviation or frequency (%).*: based on ais score. table 2: comparing the baseline characteristics of studied participants between scooter (vespa) and standard (street) motorcycle riders variable motorcycle type p standard (n:162) scooter (n:162) fracture location none 7 (4.3) 20 (12.3) 0.001 upper extremity 65 (40.1) 82 (50.7) 0.88 lower extremity 90 (55.6) 60 (37) 0.012 head and neck 11 (6.8) 16 (9.9) 0.081 chest 9 (5.6) 14 (8.6) 0.14 shoulder, elbow & hand 45 (27.7) 52 (32.1) 0.11 abdominal, lower back, and pelvic 5 (3.1) 6 (3.7) 0.21 hip and thigh 5 (3.1) 4 (2.5) 0.38 knee and midfoot 57 (35.2) 34 (21 ) 0.001 ankle and foot 16 (15.9) 16 (9.9) 0.018 minor damage 5 (3.1) 20 (12.3) 0.001 outcomes death 18 (11.1) 16 (9.9) 0.084 hospital stay (day) 6.6 ± 4.9 5.1±3.8 0.076 admission to icu 29 (17.9) 16 (9.9) 0.033 data are presented as mean ± standard deviation or frequency (%). icu: intensive care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. bahardoust et al. 8 table 3: multivariate logistic regression analysis of factors associated with severe and critical trauma in motorcycle riders variable odd 95% ci p age < 24 years 2.56 1.46-3.66 0.012 speed ≥ 60 (km/h) 3.56 2.12-5.10 0.001 use of helmet 0.66 0.46-0.87 0.001 motorcycle (standard type) 1.47 1.07-1.98 0.018 odd: adjusted odds ratio, ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strengths and limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e6 or i g i n a l re s e a rc h nifekalant versus amiodarone for out-o f-hospital cardiac arrest with refractory shockable rhythms; a post hoc analysis hiraku funakoshi1,2∗, shotaro aso3, yosuke homma1, ryuta onodera1, yoshio tahara4 1. department of emergency and critical care medicine, tokyobay urayasu ichikawa medical center, 3-4-32 todaijima, urayasu, chiba 279-0001, japan. 2. department of clinical epidemiology and health economics, school of public health, graduate school of medicine, the university of tokyo. 7-3-1 hongo, bunkyo-ku, tokyo 113-8555, japan. 3. department of biostatistics & bioinformatics, graduate school of medicine, the university of tokyo 7-3-1 hongo, bunkyo-ku, tokyo 113-0033, japan. 4. department of cardiovascular medicine, national cerebral and cardiovascular center, 6-1 kishibe-shimmachi, suita, osaka 564-8565, japan. received: november 2021; accepted: november 2021; published online: 1 january 2022 abstract: introduction: it is still unclear that which anti-arrhythmics are adequate for treating refractory dysrhythmia. this study aimed to compare amiodarone and nifekalant in management of out-of-hospital cardiac arrest cases with refractory shockable rhythm. methods: this was a post hoc analysis of cases registered in a nationwide, multicentre, prospective registry that includes 288 critical care medical centres in japan. from june 2014 to december 2017, we included all out-of-hospital cardiac arrest patients aged ≥18 years who presented with refractory arrhythmia (sustained ventricular fibrillation or ventricular tachycardia following delivery of at least two defibrillator shocks) and treated with nifekalant or amiodarone after arrival to hospital. overlap weight was performed to address potential confounding factors. results: 1,317 out-of-hospital cardiac arrest patients with refractory arrhythmia were enrolled and categorized into amiodarone (n = 1,275) and nifekalant (n = 42) groups. after overlap weight was performed, there were no significant intergroup differences in increased the rate of admission after return of spontaneous circulation [–5.9% (95%ci: –7.1 to 22.4); p = 0.57], 30-day favourable neurological outcome [0.1% (95%ci: –14 to 13.9); p = 0.99], and 30-day survival [–3.9% (95% ci: –19.8 to 12.0); p = 0.63]. conclusion: this nationwide study showed that nifekalant was not associated with improved outcomes regarding admission after return of spontaneous circulation, 30-day survival, and 30-day favourable neurological outcome compared with amiodarone. keywords: anti-arrhythmia agents; cardiopulmonary resuscitation; nifekalant; ventricular fibrillation; ventricular flutter cite this article as: funakoshi h, aso s, homma y, onodera r, tahara y. nifekalant versus amiodarone for out-of-hospital cardiac arrest with refractory shockable rhythms; a post hoc analysis. arch acad emerg med. 2022; 10(1): e6. https://doi.org/10.22037/aaem.v10i1.1425. 1. introduction approximately 12% of patients with out-of-hospital cardiac arrest (ohca) survive until discharge from the hospital. in spite of widespread early bystander cardiopulmonary resuscitation (cpr) and automated external defibrillator (aed) ∗corresponding author: hiraku funakoshi; department of emergency and critical care medicine, tokyobay urayasu ichikawa medical center, 3-4-32 todaijima, urayasu, chiba 279-0001, japan. telephone: +81473513101, fax: +81-473526237, email: hfunakoshi-tbmc@umin.org, orcid: http://orcid.org/0000-0001-5828-6986. use, the overall survival from ohca remains low and 20% of patients with ohca who survive develop irreversible neurological disability (1). it was previously reported that only 8% of patients were discharged from the hospital after recovering to a condition in which they could live without any support (1). thus, the need for a standardized approach to cpr to improve patients’ outcomes after cardiac arrest has been considered for many years. for refractory arrhythmia, which is defined as sustained ventricular fibrillation (vf) or pulseless ventricular tachycardia (vt) despite performing defibrillation twice, administration of anti-arrhythmics following administration of adrenaline this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. funakoshi et al. 2 and defibrillation is recommended, and the guidelines recommend amiodarone administration (2, 3). although the benefits of administration of anti-arrhythmics are limited, anti-arrhythmics are key for return of spontaneous circulation (rosc) in cases of refractory arrhythmia (4). nifekalant, which was developed and approved in japan in 1999, is a class iii anti-arrhythmic agent per the vaughan williams classification. although a meta-analysis suggested that nifekalant may be effective in improving short-term and long-term survival, the only study that had a low risk of bias among those included in the meta-analysis had shown no benefit from nifekalant. it had also stated that the effect of amiodarone on either of these outcomes could not be confirmed (5). due to this limitation, nifekalant was an alternative to amiodarone for refractory arrhythmias in the international liaison committee on resuscitation (ilcor) consensus and nifekalant was not mentioned in the guidelines of the american heart association (aha) and european resuscitation council (erc) (2, 3). in addition, the guidelines released by the japan resuscitation council ( jrc) in 2015 recommend the use of amiodarone over nifekalant (6). a large study using a japanese nationwide in-hospital patient administrative database conducted after the publication of these guidelines compared the effectiveness of nifekalant and amiodarone and found no difference between the two anti-arrhythmics (7). however, the study did not include information on prehospital care, such as bystander witness, bystander cpr, and aed use, which is the most important determinant of the prognoses of patients with cardiorespiratory arrest (8-10). on the other hand, a previous study using prehospital data does not include precise information on in-hospital treatment, and the dose of amiodarone was not consistent in the study. therefore, evaluation of the effectiveness of nifekalant in the context of data on both preand in-hospital care have been the remaining issue. based on the above-mentioned points, this study aimed to compare amiodarone and nifekalant in management of out-of-hospital cardiac arrest cases with refractory shockable rhythm in terms of patients’ admission after rosc, 30day favourable neurological outcome (cerebral performance category 1 or 2), and 30-day survival. 2. methods 2.1. study design and setting this study is a post hoc analysis of cases registered in the japanese association for acute medicine out-of-hospital cardiac arrest ( jaam-ohca) registry, which is a nationwide, multi-centre prospective registry that includes 288 critical care medical centres in japan. the detailed study protocol has been previously described (11). all patients with cardiorespiratory arrest in a prehospital setting who were then transported to a member institution are included in the registry. to allow refusal for inclusion in the registry by patients or their family members, a special committee and each participating institution made available a document regarding opt-out consent on the website and/or a notice board in the emergency department. therefore, the requirement for informed consent from patients was waived. the registry was approved by the ethics committee of kyoto university (reference number is r1045), and each hospital also approved the jaam-ohca registry protocol as necessary. 2.2. emergency medical system in japan in japan, all patients with cardiorespiratory arrest are transported by an emergency medical system (ems) team, because ems providers are not allowed to terminate resuscitation in the field unless there are obvious signs of death (e.g. lividity or rigor mortis) (12). ems teams in japan provide defibrillation via an aed and protect the airway using supraglottic airway or endotracheal intubation and administer adrenaline per remote instruction from a doctor. however, ems providers are not permitted to administer any antiarrhythmics. 2.3. participants this study included all patients in the jaam-ohca registry from june 2014 to december 2017. of these patients, we included all ohca patients aged ≥18 years in whom refractory arrhythmia was treated with nifekalant or amiodarone. we excluded patients who received both nifekalant and amiodarone. 2.4. data gathering the jaam-ohca registry includes both preand posthospitalization data. prehospitalization data were obtained from the all-japan utstein registry of the fire and disaster management agency (fdma) as previously reported (12, 13). in-hospital data were collected via an internet-based system by physicians or medical staff at each institution. the jaamohca registry committee integrated the prehospital and inhospital data, as previously described (12). the protocol was approved by the institutional review board of each participating hospital. during the study period, anonymized data were entered into the web form by the medical staff in charge of the patient and were finally confirmed by the jaam-ohca registry committee, which consists of specialists in emergency medicine and epidemiology. a committee member returned any incomplete data forms to the institution submitting the form and the data form was filled out as completely as possible. in-hospital data were systemically combined with prehospital resuscitation data obtained from the all-japan utstein registry of the fdma, by using the five key items in both datasets: prefecture, emergency call time, age, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e6 sex, and cerebral performance category (cpc) 1 month after the ohca (13). 2.5. exposure and outcome measures the exposure was the administration of nifekalant or amiodarone. the responsibility for selecting the anti-arrhythmic medication was entirely entrusted to each physician or institution. although there are no specific protocols for refractory arrhythmia in the jaam-ohca registry, most facilities follow the guidelines published by the jrc, which comply with ilcor, for performing cpr. the primary outcome measure of interest was admission after rosc. the secondary outcomes were 30-day survival and 30-day favourable neurological outcome. a favourable neurological outcome was defined as a cpc score of 1 or 2 (11). the cpc score scale accounts for five outcomes: 1, good cerebral recovery; 2, moderate cerebral disability; 3, severe cerebral disability; 4, coma or vegetative state; and 5, death/brain death (13). 2.6. statistical analysis all descriptive statistics were reported as number (%) or mean ± standard deviation. for comparison of characteristic variables among cohorts, independent-sample t-tests were used for numeric variables, while chi-squared tests were used for categorical variables. overlap weight was performed to address potential confounding (14, 15). a propensity score for nifekalant administration was estimated using a multivariable logistic regression model containing age, sex, witness status, presence of a bystander who performed cpr, aetiology of cardiac arrest (cardiac or not), prehospital adrenaline administration, prehospital airway management, prehospital aed use, response time, physicians, and hospital number. based on previous studies, these variables would be relevant to treatment assignment (8-10). overlap weight is defined as 1propensity score for patients receiving nifekalant and propensity score for patients receiving amiodarone. by applying overlap weights for each patient, we adjusted for the patients’ backgrounds and compared the outcomes. we used absolute standardized differences to evaluate differences in patient characteristics between the groups. we regarded an absolute standardized difference of <0.1 as an acceptable balancing of covariates between the groups (16). although data on in-hospital treatments or interventions (veno-arterial extracorporeal membrane oxygenation (va-ecmo), percutaneous coronary intervention (pci), and targeted temperature management (ttm)) were collected, these variables were not included in the variables for the estimation of the propensity score, because we assumed that these treatments are administered after rosc (17). in addition, we also performed a series of sensitivity analyses to examine the robustness of our inference: 1) based on the assumption that the decision to use these three treatments (vaecmo, pci, and ttm) is made prior to admission, we calculated propensity score including the three treatments and performed an analysis with overlap weight. 2) analysis was performed excluding patients with ecmo to avoid reverse causation; because it is difficult to identify whether patients with ecmo had resumed spontaneous circulation at the time of admission or not. stata/se 16.0 (stata corp, college station, tx, usa) was used for data analyses. the threshold for significance was set at p < 0.05. 3. results 3.1. baseline characteristics during the study period, 1,374 ohca patients with refractory arrhythmia were enrolled in this study. of these patients, 1,317 eligible patients were included in this analysis after excluding 57 patients who had received both nifekalant and amiodarone. these patients were categorized into amiodarone (n = 1,275) and nifekalant (n = 42) groups. table 1 compares the baseline characteristics of studied cases between nifekalant and amiodarone groups. the mean patients’ age was 64.0 ± 15.4 years (20.7% female). propensity score based on the variables listed in methods section are presented in figure 1. after overlap weight adjustment for treatment with nifekalant, baseline patient characteristics were well-balanced between the two groups, as shown in table 2 (p < 0.01). 3.2. comparing outcomes in crude data, the proportions of admission after rosc in nifekalant group were not significantly different from those in amiodarone group (64.3% vs. 56.6%, p = 0.32). the proportions of the favourable 30-day neurological outcome were significantly higher among patients who received nifekalant compared to patients for whom amiodarone was administered (23.8% vs. 10.4%, p < 0.01). the proportions of 30-day survival in nifekalant group were not significantly different from those in amiodarone group (31.0% vs 20.1%, p = 0.09). with overlap weight, nifekalant use was not associated with improved outcomes (hospital admission after rosc: risk difference, –5.9% (95% ci: -26.7 to 14.8); favourable 30-day neurological outcome: risk difference, 0.1% (95% ci: –14 to 13.9); 30-day survival: risk difference, –3.9% (95% ci: –19.8 to 12.0) (table 3)). 3.3. key in-hospital treatments table 4 shows differences in key in-hospital treatments or interventions between the two groups. the proportions of patients who received veno-arterial extracorporeal membrane oxygenation (va-ecmo), percutaneous coronary interventhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. funakoshi et al. 4 table 1: comparing the baseline characteristics of studied cases between amiodarone (n = 1,275) and nifekalant (n = 42) groups variables total amiodarone nifekalant sd p age (year) 64.0 ± 15.4 64.1 ±15.4 60.1±16.3 0.25 0.14 gender (female) 273 (20.7) 267 (20.9) 6 (14.3) 0.18 0.30 witness 929 (70.5) 900 (70.6) 29 (69.0) 0.03 0.83 bystander cpr 581 (44.1) 564 (44.2) 17 (40.5) 0.08 0.63 aed use 933 (74.4) 897 (70.4) 36 (85.7) 0.42 0.02 prehospital adrenaline 495 (37.6) 485 (38.1) 10 (23.8) 0.31 0.06 airway equipment use 656 (59.3) 645 (50.6) 11 (26.2) 0.24 0.26 physician on scene 280 (21.3) 273 (21.4) 7 (16.7) 0.12 0.46 presumed cause of cpa 1,138(86.4) 1,098(86.1) 40 (95.2) 0.32 0.09 call to dispatch (minute) 8.5 ±3.5 8.6 ± 3.5 7.8 ± 2.4 0.24 0.15 data are presented as mean ± standard deviation or number (%). abbreviations: aed, automated external defibrillator; cpa, cardiopulmonary arrest; cpr, cardiopulmonary resuscitation; sd, standardized difference. table 2: overlap propensity score-weighted characteristics in amiodarone (n = 1,275) and nifekalant (n = 42) groups variables amiodarone nifekalant sd age (year) 61.9 ±15.9 61.9 ± 17.5 <0.01 female sex 9.0 9.0 <0.01 witness 73.8 73.8 <0.01 bystander cpr 43.8 43.8 <0.01 aed use 82.4 82.4 <0.01 prehospital adrenaline 26.6 26.6 <0.01 airway equipment use 48.7 48.7 <0.01 physician on scene 9.1 9.1 <0.01 presumed cause of cpa 91.0 91.0 <0.01 call to dispatch (minute) 7.72 ± 2.53 7.72 ± 2.43 <0.01 data are presented as mean ± standard deviation or number (%). abbreviations: aed, automated external defibrillator; cpa, cardiopulmonary arrest; cpr, cardiopulmonary resuscitation; sd, standardized difference. table 3: comparisons of outcomes between amiodarone (n = 1,275) and nifekalant (n = 42) groups variables amiodarone nifekalant rd (95% ci) unadjusted analysis hospital admission after rosc 56.6 64.3 7.6 (–7.1 22.4) 30-day favourable neurological outcome 10.4 23.8 13.5 (0.46 26.5) 30-day survival 20.1 31.0 10.9 (–3.3 25.0) weighted analysis hospital admission after rosc 62.1 56.2 –5.9 (–26.7 -14.8) 30-day favourable neurological outcome 12.8 12.8 0.1 (–14.0 13.9) 30-day survival 21.2 17.3 –3.9 (–19.8 -12.0) data are presented as percentage. abbreviations: rosc, return of spontaneous circulation; rd: risk difference; ci: confidence interval. tion (pci), and target temperature management (ttm) were higher in the nifekalant group. intergroup differences in these proportions were not significant. although the proportions of the patients who received va-ecmo were wellbalanced after overlap weight, the proportions of those who received the percutaneous coronary intervention and targeted temperature management remained different between the two groups (table 4). in the sensitivity analysis, va-ecmo, pci, and ttm were well-balanced between the two groups with overlap weight using another propensity score, and nifekalant use showed no significant association with higher proportion of 30-day favorable neurological outcome [0.3% (95% ci: –14.2 to 13.6)] and 30-day survival [–4.6% (95% ci: –20.6 to 11.3)]. as with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e6 figure 1: the histogram of propensity score distribution in each treatment group. table 4: comparing the treatments and interventions after return of spontaneous circulation between amiodarone (n = 1275) and nifekalant (n = 42) groups treatment un-weighted weighted amiodarone nifekalant sd p amiodarone nifekalant sd va-ecmo 40.5 50.0 0.19 0.22 46.4 47.2 0.02 pci 23.5 31.0 0.17 0.27 27.2 21.6 -0.13 ttm 29.1 47.6 0.38 <0.01 32.4 38.5 0.13 data are expressed as %. pci, percutaneous coronary intervention; ttm, target temperature management; va-ecmo, veno-arterial extracorporeal membrane oxygenation. sd: standardized difference. the results of main analysis, after excluding patients with ecmo, nifekalant use showed no significant association with higher proportion of admission after rosc [risk difference: –0.4% (95% ci: –20.6 to 13.0)]. 4. discussion in this nationwide study, we compared the proportions of admission after rosc and 30-day outcomes between patients treated with nifekalant and those treated with amiodarone after ohca associated with refractory arrhythmias. after adjusting for patients’ background, including both pre-hospital and in-hospital data by overlap weight, no significant difference in the proportions of admission after rosc and 30day favourable outcomes was found between nifekalant and amiodarone administration after arrival in hospital. this study compared the effectiveness of nifekalant with that of amiodarone by using data including detailed prehospital care data from a nationwide registry of patients with cardiorespiratory arrest. amiodarone and nifekalant are both this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. funakoshi et al. 6 classified as class iii antiarrhythmic agents (potassium channel blockers) in the vaughan-williams classification. however, these two antiarrhythmic drugs have different pharmacological characteristics (18, 19). amiodarone is not only a potassium channel blocker but also has blocking effects on other ion channels such as sodium and calcium channels and α and β receptors. as a result of these multichannel blocking effects, amiodarone has negative inotropic and vasodilatory effects, which may in turn negatively affect the haemodynamic status for coronary artery flow and after rosc in ohca patients. on the other hand, nifekalant is a pure potassium channel blocker that does not block sodium or calcium channels (20). in a study conducted using an animal model, nifekalant use decreased the defibrillation threshold for ventricular fibrillation (21). from these pharmacological points of view, nifekalant could have advantages over amiodarone for the treatment of refractory arrhythmia. however, clinical studies are limited. amino et al. reported that nifekalant and amiodarone were both associated with improved 24-hour survival compared to lidocaine in ohca patients with refractory arrhythmia (22). however, this study did not perform a direct comparison between nifekalant and amiodarone. in addition, because the dose of amiodarone was not standardized during the study period, only approximately 200 people received the international standard dose of 300 mg (22). in this study, only 3.2% (57/1374) of the patients received nifekalant. because nifekalant was recommended alongside amiodarone for refractory arrhythmias until 2005, the use of nifekalant was relatively common in previous studies (7, 22). the removal of nifekalant from the recommendations in the 2015 guideline of the aha could result in a decrease in the use of nifekalant (2). in the 2020 guideline of the aha, the use of nifekalant for refractory arrhythmias has not been included. thus, japan is a rare country in which nifekalant was included as an alternative to amiodarone to treat ohca patients with refractory arrhythmia. high-quality studies with sufficient size are warranted to determine which antiarrhythmic drugs are effective for the treatment of refractory arrhythmias with greater confidence across the country. 5. limitations there are several limitations in this study. first, as with any observational study, there was a risk of selection bias. especially in this study, the number of patients in nifekalant group was limited, which may lead to differences in patient distribution. as a result, comparability may be compromised. in addition, there was a risk of confounders. to overcome this limitation, we performed overlap weight, and all measured confounding factors were well balanced among each group, yet the risk of unmeasured confounder remained. second, the power of this study was low due to the small number of patients in the nifekalant group. however, it has been pointed out that it is inappropriate to judge the appropriateness of a study based on its post hoc power, and the results should be interpreted with caution (25). third, we could not adjust for treatment and intervention after rosc and during admission. as described in the results, the proportions of patients who received target temperature management and percutaneous coronary intervention differed between the nifekalant and amiodarone groups. however, even in randomized controlled trials, statistical adjustment for factors after group allocation could introduce over-adjustment bias and could inappropriately dilute the true relationship between the exposure and outcome in the study (17). therefore, we conducted a sensitivity analysis using propensity score including the three treatments and performed an analysis with overlap weight based on the assumption that the decision to use these three treatments (va-ecmo, pci, and ttm) is made prior to admission. the result is consistent, which may support the robustness of the results. fourth, although dose and timing of anti-arrhythmics is an important factor, jaam-ohca registry does not include the time of administration or the dose of anti-arrhythmics. 6. conclusion this nationwide study showed that nifekalant was not associated with improved outcomes regarding admission after return of spontaneous circulation, 30-day survival, and 30day favourable neurological outcome compared with amiodarone. 7. list of abbreviations aed, automated external defibrillator; aha, american heart association; cpc, cerebral performance category; cpr, cardiopulmonary resuscitation; ems; emergency medical system; erc, european resuscitation council; fdma, the fire and disaster management agency; ilcor, international liaison committee on resuscitation; jaam-ohca, the japanese association for acute medicine out-of-hospital cardiac arrest; jrc, japan resuscitation council; ohca, outof-hospital cardiorespiratory arrest; rosc, return of spontaneous circulation; vf, ventricular fibrillation; vt, ventricular tachycardia 8. declarations 8.1. acknowledgments none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e6 8.2. author contribution hf and sa performed the quantitative analysis and drafted the manuscript, which was critically reviewed by all of the authors. hf, yh, ro and yt planned the study and analyzed and interpreted the data. all authors read and approved the final manuscript. 8.3. funding the authors received no financial support for the research, authorship and/or publication of this article. 8.4. conflict of interest the authors declare that they have no competing interests. 8.5. ethical consideration the study was conducted according to the ethical guidelines of the declaration of helsinki. the patients’ information was anonymized and de-identified prior to the analysis, thus the informed consent of the patient was waived. references 1. benjamin ej, muntner p, alonso a, bittencourt ms, callaway cw, carson ap, et al. heart disease and stroke statistics-2019 update: a report from the american heart association. circulation. 2019;139(10):e56-e528. 2. link ms, berkow lc, kudenchuk pj, halperin hr, hess ep, moitra vk, et al. part 7: adult advanced cardiovascular life support: 2015 american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2015;132(18 suppl 2):s444-64. 3. soar j, nolan jp, bottiger bw, perkins gd, lott c, carli p, et al. european resuscitation council guidelines for resuscitation 2015: section 3. adult advanced life 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out-of-hospital cardiac arrest. circulation. 2012;126(5):589-97. 13. jennett b, bond m. assessment of outcome after severe brain damage. lancet. 1975;1(7905):480-4. 14. li f, thomas le, li f. addressing extreme propensity scores via the overlap weights. american journal of epidemiology. 2019;188(1):250-7. 15. thomas le, li f, pencina mj. overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial. jama. 2020;323(23):2417-8. 16. austin pc. using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. communications in statistics simulation and computation. 2009;38(6):1228-34. 17. schisterman ef, cole sr, platt rw. overadjustment bias and unnecessary adjustment in epidemiologic studies. epidemiology. 2009;20(4):488-95. 18. singh bn, vaughan williams em. the effect of amiodarone, a new anti-anginal drug, on cardiac muscle. british journal of pharmacology. 1970;39(4):657-67. 19. pantazopoulos in, troupis gt, pantazopoulos cn, xanthos tt. nifekalant in the treatment of life-threatening ventricular tachyarrhythmias. world journal of cardiology. 2011;3(6):169-76. 20. nakaya h, tohse n, takeda y, kanno m. effects of ms551, a new class iii antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes. british journal of pharmacology. 1993;109(1):15763. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. funakoshi et al. 8 21. murakawa y, yamashita t, kanese y, omata m. can a class iii antiarrhythmic drug improve electrical defibrillation efficacy during ventricular fibrillation? journal of the american college of cardiology. 1997;29(3):688-92. 22. amino m, inokuchi s, nagao k, nakagawa y, yoshioka k, ikari y, et al. nifekalant hydrochloride and amiodarone hydrochloride result in similar improvements for 24hour survival in cardiopulmonary arrest patients: the sos-kanto 2012 study. journal of cardiovascular pharmacology. 2015;66(6):600-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion list of abbreviations declarations references archives of academic emergency medicine. 2022; 10(1): e76 rev i ew art i c l e complications of covid-19 vaccines during pregnancy; a systematic review seyedahmad seyedalinaghi1, mehrzad mohssenipour1, solmaz saeidi2, pedram habibi1, mohsen dashti3, newsha nazarian4, tayebeh noori5, zahra pashaei1, amirbehzad bagheri6, afsaneh ghasemzadeh3, amir masoud afsahi7, narjes aghaie8, paniz mojdeganlou9, ghazal arjmand9, ghazal zargari10, roshanak modiri1, hengameh mojdeganlou11, armin razi12, esmaeil mehraeen 13∗, omid dadras1,14 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. department of nursing, khalkhal university of medical sciences; khalkhal, iran. 3. department of radiology, tabriz university of medical sciences, tabriz, iran. 4. school of medicine, islamic azad university, tehran, iran. 5. department of health information technology, zabol university of medical sciences, zabol, iran. 6. student research committee, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 7. department of radiology, school of medicine, university of california, san diego (ucsd), california, usa. 8. school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 9. shahid beheshti university of medical sciences, tehran, iran. 10.school of medicine, iran university of medical sciences, tehran, iran. 11.department of pathology, urmia university of medical sciences, urmia, iran. 12.school of medicine, tehran university of medical sciences, tehran, iran. 13.school of medicine, tehran university of medical sciences, tehran, iran. 14.department of global public health and primary care, graduate school of medicine, university of bergen, bergen, norway. received: july 2022; accepted: august 2022; published online: 24 september 2022 abstract: introduction: rare serious complications have been documented after covid-19 vaccination as clinical research proceeded and new target populations, such as children and pregnant women, were included. in this study, we attempted to review the literature relevant to pregnancy complications and maternal outcomes of covid-19 immunization in pregnant women. methods: we searched the databases of pubmed, scopus, cochrane, and web of science on 31 august 2022. the records were downloaded and underwent a two-step screening; 1) title/abstract and then 2) full-text screening to identify the eligible studies. we included english original studies that evaluated the adverse effects of covid-19 vaccines during pregnancy. information such as the type of study, geographical location, type of vaccine injected, gestational age, maternal underlying diseases, and complications following the vaccination were extracted into pre-designed tables. results: according to the findings of included studies, in most of them vaccination had a positive impact and no negative effects were observed. also, no medical history was reported in 11 articles, and pregnant women had no underlying diseases. some serious adverse events were reported after vaccination, including miscarriage, paresthesia, uterine contraction, vaginal bleeding, preterm birth, major congenital anomalies, intrauterine growth restriction, and seizure. conclusion: because of limited data availability and the cross-sectional design of most studies, we could neither infer causation between vaccines and incidence of adverse effects nor comment with certainty about any possible adverse outcome of covid-19 vaccines in vaccinated pregnant women. consequently, more longitudinal and experimental studies are needed to define the exact adverse effects of covid-19 vaccines in pregnant women. keywords: drug-related side effects and adverse reactions; covid-19; covid-19 vaccines; pregnancy; sars-cov-2 cite this article as: seyedalinaghi sa, mohssenipour m, saeidi s, habibi p, dashti m, et al. complications of covid-19 vaccines during pregnancy; a systematic review. arch acad emerg med. 2022; 10(1): e76. https://doi.org/10.22037/aaem.v10i1.1622. ∗corresponding author: esmaeil mehraeen, department of health information technology, khalkhal university of medical sciences, khalkhal, iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 2 1. introduction putting an end to the pandemic has been the ultimate goal of humanity since the commencement of the covid-19 pandemic and substantial efforts have been made to develop an effective vaccine to curb the virus ever since. as a result of advancements in covid-19 prevention research, many countries have developed coronavirus vaccines (1-3). the development of these vaccines, each of which inhibit coronavirus infection using a different mechanism, raises the hopes of ending the covid-19 pandemic. although covid-19 vaccination lowers the chance of acquiring the coronavirus and its mortality with no or minimal major side effects (4, 5), rare serious complications have been documented after covid19 vaccination as clinical research proceeded and new target populations, such as children and pregnant women, were included (6). serious side effects of vaccines have been reported in the past, and such side effects have not been specific to covid19 vaccines. for instance, the influenza vaccine may have some serious side effects such as guillain-barré syndrome and acute transverse myelitis (7-9). likewise, covid-19 immunization may potentially cause acute transverse myelitis in rare cases (10). it has been shown that pregnant women could be at a higher risk of severe covid-19 infection (11) and covid-19 infection in a pregnant mother is more likely to harm her or her fetus. it appeared that caesarean sections and premature deliveries may be more likely in severe covid-19 among pregnant patients (12). these findings emphasize the important role of covid-19 immunization in pregnant women. therefore, it is of paramount importance to explore the possible side effects of covid-19 vaccination in pregnant women using available data. since pregnant women were not included in initial vaccine trials, limited information exists on the vaccine’s efficacy and safety during pregnancy. although several studies reported different side effects of covid-19 vaccines in the general population, there is a scarcity of literature on pregnant women (3, 13, 14). therefore, more research concerning the effectiveness and possible side effects of covid19 vaccination in pregnant women is needed. due to the novelty of covid-19 vaccination, we attempted to review the literature relevant to pregnancy complications and maternal outcomes of covid-19 immunizations in this systematic review. postal code: 5681761351, tel: +98-45-32426801, fax: +98-45-32422305, e-mail: es.mehraeen@gmail.com. 2. methods 2.1. search strategy this systematic review was reported in adherence to the preferred reporting items for systematic reviews and metaanalysis (prisma) checklist. we searched the databases of pubmed, cochrane, scopus, and web of science on 31 august 2022. to develop our search strategy, we checked the keywords from previous studies and the medical subject headings (mesh) website. the search strategies for each database are reported below as an example: (((covid-19 [title] or sars-cov-2 [title] or novel coronavirus [title] or 2019-ncov [title]) and (vaccine [title] or vaccination [title] or vaccinated [title] or immunization [title])) and (side effect [title] or adverse effect [title] or adverse reaction [title] or adverse event [title] or safety [title])) and (pregnancy [title] or pregnant [title] or gestation [title] or gestational [title]) pico 1. population: pregnant women 2. intervention: receiving covid-19 vaccines 3. comparison: not receiving covid-19 vaccines 4. outcomes: various adverse events inclusion/exclusion criteria we included english original studies that evaluated the adverse effects of covid-19 vaccines during pregnancy. we did not impose any restrictions regarding the date of the studies or the length of their follow-up in this systematic review. the exclusion criteria were the following: 1) non-original studies (reviews, opinions, etc.) 2) non-english studies 3) studies not related to the aim of this systematic review (e.g. not related to covid-19 vaccines, not related to pregnancy, did not measure adverse effects, etc.) 4) studies not conducted in humans 5) abstracts or studies that lacked available full-texts 2.2. study selection process two independent researchers screened the studies in a twostep method. first, they screened the studies based on the contents of their title and abstracts. then, the eligible studies entered the second step, which was the full-text screening. studies that adhered to the inclusion criteria in both steps were finally included in this systematic review. in case of any disagreements between the researchers, they asked the opinion of another researcher to resolve the matter. 2.3. data extraction three independent researchers extracted the data of the included studies into a pre-designed word table (one third of the studies were given to each researcher). the following information were extracted: type of the study, country, study this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e76 population, vaccine type, gestational age (week/trimester), past medical history, and reported complications (typical side effects or serious adverse events). another researcher checked the extracted data and corrected any possible mistakes. the extracted data were qualitatively synthesized, but we did not aim to perform statistical analysis as the study is not a meta-analysis. 2.4. risk of bias/quality assessment we assessed the risk of bias/quality of the studies using the newcastle-ottawa scale (nos) checklist. this scale allocates a 0-9 score to each study based on selection, comparability, and exposure/outcome (15). studies that scored 4 or below were considered of poor quality. 3. results a total of 1447 relevant studies were identified applying different combinations of keywords and search strategies in online databases. following the initial review, 408 duplicates were deleted. the remaining articles (n=1039) were screened by two independent researchers based on their title and abstract. in the next step, the full-text of 470 remaining articles were thoroughly read and based on eligibility criteria, the most relevant records were selected for final qualitative synthesis. during data extraction, 450 articles were removed because they were non-english articles (n=25), papers with the lack of experimental data (n=392), and animal or pure labbased studies (n=33). finally, 20 studies met the inclusion criteria and were included (figure 1). variables including type of vaccine, sample population, age, complications, gestational age, and prior medical history were extracted and are reported in table 1. included articles investigated the side effects and adverse events of covid-19 vaccines including pfizer-biontech, moderna, and janssen. the study designs included case report, case series, and cross-sectional and cohort studies. according to the findings of included studies, in most cases vaccination had a positive impact and no negative effects were observed. there were no notable differences between the vaccinated and unvaccinated groups in 11 studies. in two studies, complications were reported more in the vaccinated group than in the unvaccinated group. in a study conducted among 390 pregnant women, paresthesia was significantly more common among vaccinated pregnant women compared to unvaccinated group. also, in those who received the 2nd dose in the third-trimester, uterine contractions were significantly more common (16). two newborn babies of 84 pregnant women who had received pfizer (49%), and moderna (51%) vaccines, were admitted to the intensive care unit to receive respiratory support. one baby received continuous positive airway pressure (cpap) and one of them had transient tachypnea of the newborn (17). no medical history was reported in 11 articles, and pregnant women had no underlying diseases. however, in a cohort study conducted on 7350 pregnant women, underlying disease of diabetes mellitus, hypertension, immunosuppression/cancer, obesity (bmi ≥30), infertility, chronic kidney disease, cardiovascular disease, and chronic obstructive pulmonary disease were reported (18, 19). in another cohort study in 84 pregnant women who were in their first (13.1%), second (46.4%), and third (40.5%) trimesters of pregnancy, diabetes mellitus, hypertension, obesity (bmi≥30), asthma, immunosuppression/cancer, and previous sars-cov-2 infection were reported as underlying diseases (17). chronic liver disease, chronic heart disease, diabetes mellitus, and hypertension in 390 pregnant women in all three trimesters of pregnancy were reported (16). the time between vaccine inoculation and the onset of adverse events of idiopathic thrombocytopenic purpura (itp) symptoms was 11 days in a woman who was in her first trimester of pregnancy (20) and it was 12 days in 30 pregnant women who were in their first (17%), second (50%), and third (33%) trimesters of pregnancy (21). in a matched cohort of 133 vaccinated and 399 unvaccinated pregnant women who had received pfizer and moderna, the rates of adverse pregnancy outcomes were similar between vaccinated and unvaccinated pregnant women: postpartum hemorrhage (9.8% vs 9%), fetus small for gestational age (12% vs 12.8%), maternal high-dependency unit or intensive care admission (6% vs 4%), neonatal intensive care unit admission (5.3% vs 5%), fetal abnormalities (2.2% vs 2.5%), and stillbirth (0% vs 0.2%). in the vaccinated group, three fetal abnormalities including spina bifida, ventriculomegaly, and hydronephrosis were reported. the spina bifida case was diagnosed before the first dose of the covid vaccine. the ventriculomegaly case was diagnosed at 37 weeks gestation with no associated brain abnormalities. the hydronephrosis appeared to be mild with no associated abnormality at birth (22). in another cohort study conducted on 827 pregnant women who received moderna (46%) and pfizer (54%) vaccines, 46 cases of spontaneous abortion, and three cases of stillbirth, premature rupture of membrane, and vaginal bleeding, each, were reported. no congenital anomalies were observed (23). in a case report, a pregnant woman who received moderna in the first trimester manifested itp symptoms including acute bruising and petechiae, she was discharged after three days of hospitalization and completely recovered following a course of steroid treatment (20). in a case-control study, 390 pregnant women who received pfizer in their first (19.5%), second (49.5%), and third (31%) trimesters, experienced the following adverse events: axillary lymphadenopathy (0.3%), paresthesia (2.3%), uterine contraction (1.3%), and vagithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 4 table 1: complications of covid-19 vaccination during pregnancy id the first author (r) type of study sample size type of vaccine gestational age (%) medical history (%) complication (%) other findings adverse events side effects 1 blakeway, h. (22) uk cohort 1328 pb, m n/a n/a spina bifida, ventriculomegaly, hydronephrosis, fetal abnormalities, postpartum hemorrhage n/a n/a 2 carrie bennett (20) usa case report 1 m first trimester n/a itp symptoms: acute bruising and petechiae n/a discharged after 3 days of hospitalization, to continue steroids for one week and taper over 6 weeks. 3 s. booksteinperetz (16) israel casecontrol 390 pb first trimester (19.5), second trimester (49.5), third trimester (31) diabetes mellitus (3.3), chronic heart disease (0.8), chronic liver disease (5.4), hypertension (0.5) axillary lymphadenopathy (0.3), paresthesia (2.3), uterine contraction (1.3), vaginal bleeding (0.3), two babies admitted to icu local pain (91.8), rash (0.8), fever (1.5), severe fatigue (25.6), arthralgia (1), myalgia (5.9), headache (4.6) paresthesia among pregnant women was significantly more common. in those who received 1st dose during the third trimester, local pain/swelling was significantly less common and in those who received 2nd in third-trimester uterine contractions were significantly more common. 4 tom t. shimabukuro (23) usa cohort 827 pb (54) m (46) n/a n/a pregnancy losses (13.9), preterm birth (9.4), small for gestational age (3.2), major congenital anomalies (2.2) n/a live-born infants=724 multiple gestation=12 5 megan e trostle (24) usa crosssectional 424 mrna first trimester (34), second trimester (54.4), third trimester (11) n/a spontaneous abortions (2.12), terminated pregnancies (0.7), intrauterine growth restriction (0.6), anomalies (1.5), preterm birth (5.9), need for nicu (15.3), small for gestational age (12.2) n/a n/a 6 regan n. theiler (28) usa cohort 2002 mrna median gestational age 32 weeks n/a no adverse events were reported. n/a n/a 7 tamar wainstock (29) israel cohort 913 pb 3rd trimester n/a no adverse events were reported. n/a n/a 8 lauren head zauche (27), usa cohort 2456 mrna prior to 20 weeks’ gestation n/a n/a n/a n/a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e76 table 1: complications of covid-19 vaccination during pregnancy id the first author (r) type of study sample size type of vaccine gestational age (%) medical history (%) complication (%) other findings adverse events side effects 9 renuka ananth (25) usa crosssectional 38 pb (52.6) m (47.4) n/a n/a seizure (2.6) sore arm or pain (97.3), fatigue (57.8), headache (50), chills (47.3), myalgia (34.2), nausea (28.9), fever (15.7), sweating (15.7), feelings of joy (10.5), rash (10.5), joint pains (7.8), swelling (7.8), flushing (7.8), reduced mental clarity (7.8), itching (5.2), decreased appetite (5.2), decreased sleep quality (5.2), palpitations or increased heart rate (5.2), heat or cold intolerance (5.2), anxiety (5.2), heartburn (5.2), muscle spasm (2.6), nasal congestion (2.6), increase in sleep (2.6), vomiting (2.6) n/a 10 kathryn j. gray (17) usa cohort 84 pb (49) m (51) trimester of first vaccine dose: first (13.1), second (46.4), third (40.5) chronic hypertension (4), diabetes mellitus or gestational diabetes (4%), bmi of >30 (12%), asthma (19), immunosuppression/cancer (4), previous sars-cov-2 infection (2) n/a injection site soreness (67.8), injection site reaction or rash (1.2), headache (9.5), muscle aches (2.4), fatigue (16.6), fever or chills (1.2), elevated heart rate, joint pain, nausea, swollen lymph node, and sore throat, joint pain, nausea, sore throat, dizziness, stomach ache, night sweats, clogged ears two newborn babies were admitted to the intensive care unit to receive respiratory support. one baby received cpap and one of them had ttn. 11 collier a-ry (21) israel cohort 30 pb (36.6) m (63.3) 1st trimester (17), 2nd trimester (50), and 3rd (33) n/a n/a fever (13.3) n/a 12 goldshtein i (18) israel cohort 7530 pb n/a obesity (bmi ≥30), infertility, cancer, hypertension, chronic kidney disease, diabetes prediabetes, cardiovascular disease, chronic obstructive pulmonary disease sars-cov-2 hospitalization (0.2), abortion (1.7), intrauterine growth restriction (0.5), stillbirth (<0.1), preeclampsia (0.3), preterm birth (<37 weeks) (5.6) headache (0.1), general weakness (0.1), stomachache (<0.1), non-specified pain (<0.1), dizziness (<0.1), rash (<0.1), eye burning or blurred vision (<0.1) there were no notable differences between the vaccinated and unvaccinated groups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 6 table 1: complications of covid-19 vaccination during pregnancy id the first author (r) type of study sample size type of vaccine gestational age (%) medical history (%) complication (%) other findings adverse events side effects 13 kachikis a (39) usa cohort 7809 pb (61.2) m (38) j (0.8) 1st trimester (23.3), 2nd trimester (47.3), 3rd trimester (26.8) n/a miscarriages (0.7), pain at the injection site, fatigue, myalgia, headache, chills, fever n/a 14 abraham b (35) qatar case report 1 (female) pb 25 ± 2 weeks hypothyroidism, mild covid-19 infection acute respiratory distress syndrome with the following signs and symptoms: hypotention, decreased o2 saturation, bilateral bronchial breath sounds, right lower lobe consolidation with extensive diffuse infiltrates in cxr, dilated pulmonary trunk and right lower lobe consolidation with an associated bilateral diffuse area of ground glass consolidation in ct scan, myocarditis, mild rise in troponin-i, tachypnea, increased white blood cell count (22.09 £ 109), increased c-reactive protein (356 mg/l), need to a short period of mechanical ventilation and steroid therapy fever, pleuritic chest pain, shortness of breath on exertion, sweating, palpitation, a healthy term male baby was born 15 benmayor bashi t (37) israel cohort 58:(32.7% receive only a single dose, 67.3% receive two doses) pb first dose: 34.5 weeks second dose: 37.0 weeks bmi ≥30 (3.6), admission to nicu (1.7) at first/second dose of vaccine: pain at injection site (24.1)/ (20.5) back pain (3.4)/0 fatigue/weakness (15.5)/ (23.0) chills (5.1)/ (12.8) myalgia (5.1)/ (12.8) fever 0/ (2.5) headache (8.6)/ (5.1) peripheral facial nerve paralysis (1.7)/0 nausea (1.7)/0 dizziness (1.7)/ (2.5) unspecified illness (5.1)/ (10.2), enhanced fetal movements perception (1.7)/0 13 days after administration of the first dose of the covid-19 vaccine the levels of covid-19 igg antibody in maternal sera of vaccinated women were positively correlated with same antibody level in cord blood sera 16 arulappen al (36) china cohort 121 mrna first trimester (4.9%), second trimester (71.9%), third trimester (23.1%) gestational diabetes mellitus (14.5%), anemia (8.1%), hyperthyroidism (1.6%), asthma (0.8%), impending eclampsia (0.8%), miscarriages (0.82%), small for gestational age (5.8%), anomalies (bilateral clubfoot, glucose-6phosphate dehydrogenase (g6pd) deficiency and sacral dimple): (2.5%) jaundice (85.8%), serious complaints during the first month of life (constipation, need for oxygen therapy because of respiratory distress syndrome) (1.7%), preterm birth (≤37 weeks) (11.7%), admission to nicu (22.5%), neonatal infection (11.7%) pain, body ache, headache, chills, shivering, and fatigue no neonatal death was reported this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e76 table 1: complications of covid-19 vaccination during pregnancy id the first author (r) type of study sample size type of vaccine gestational age (%) medical history (%) complication (%) other findings adverse events side effects 17 blakeway h (38) uk cohort 1328v (vaccinated: 140, unvaccinated: 1188) pb (90.7%), viral vector vaccine (9.3%) 2nd trimester (14.3%), 3rd trimester (85.7%) obesity (bmi >30 kg/m2) (10.7%) smoker (0.7%) alcohol use (0.7%) pregestational diabetes mellitus (4.3%) antenatal medication (32.9%) hypertension on medication (9.3%) twin pregnancy (2.9%) high-dependency unit admission: was 2% more in vaccinated people than non-vaccinated people, neonatal intensive care unit admission: was 0.3% more in vaccinated people than non-vaccinated people fever: was 2.7% more in vaccinated people than non-vaccinated people postpartum hemorrhage: was 0.8% more in vaccinated people than non-vaccinated people small for gestational age at birth: were equal fetal abnormalities: were 0.3% less in vaccinated people than in non-vaccinated people instrumental delivery: was 5.3% more in vaccinated people than non-vaccinated people 18 peretzmachluf r (19) israel cohort 3240 pb n/a obesity=bmi ≥30(30.7), hypertension (1), diabetes (1) gestational diabetes (13.7), preeclampsia (1.2), small for gestational age (12.8), premature pre-labor rupture of membranes (3.1), preterm birth (6), maternal fever (1.7), neonate respiratory complication (1.9), neonate respiratory distress syndrome (0.5), neonate mechanical ventilation (0.8), nicu hospitalization (2.7), neonate hypoglycemia (4.9) n/a significantly decreased percentage of meconiumstained amniotic fluid in the vaccinated group 19 toussiacohen s (40) israel cohort 162 pb n/a autoimmune disease(19.7) n/a rash/local pain/local swelling (82.7), gastrointestinal symptoms (12.9), fever (9.2), weakness and fatigue (47.5), myalgia (23.4), axillary lymphadenopathy (4.9), remote lymphadenopathy (6.1), paresthesia (4.9), headache (4.9) n/a 20 moro pl (41) usa cohort 323 pb, m n/a n/a spontaneous abortion (26), vaginal bleeding (2.5), still birth (1.5), preeclampsia (1.2), preterm delivery (0.6), neonatal death (0.3), birth defects (0.6), nicu admission (0.9) headache, fatigue, pyrexia, pain, chills, nausea, pain in extremity, dizziness, injection site pain, vomiting n/a nicu: neonatal intensive care unit; icu: intensive care unit; sga: small for gestational age; pb: pfizerbiontech; m: moderna; j: janssen; n/a: not available; itp: idiopathic thrombocytopenic purpura; bmi: body mass index; cxr: chest x-ray; cpap: continuous positive airway pressure; ttn: transient tachypnea of the newborn; ct: computed tomography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 8 figure 1: flow diagram of included studies. nal bleeding (0.3%) (16). in other included studies, adverse events were as follows: spontaneous abortions, terminated pregnancies, intrauterine growth restriction, anomalies, preterm birth, need for neonatal intensive care unit (nicu), fetus small for gestational age (24), seizure (25), sars-cov-2 hospitalization, abortion, stillbirth, preeclampsia (18), and miscarriages (26). the main local side effect was injection site pain, and the main systemic side effect was fever. other local and systemic side effects were as follows: rash, fever, severe fatigue, arthralgia, myalgia, headache, sore arm or pain, fatigue, chills, nausea, vomiting, sweating, feelings of joy, joint pain, swelling, flushing, reduced mental clarity, itching, decreased appetite, decreased sleep quality, palpitations or increased heart rate, heat or cold intolerance, anxiety, heartburn, muscle spasm, nasal congestion, increase in sleep, swollen lymph node and sore throat, dizziness, stomachache, clogged ears, general weakness, non-specified pain, and eye burning or this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e76 blurred vision (16-18, 25, 26). the results of the risk of bias assessment are presented in table 2. the most common encountered problem was the lack of adequate matching for cases and controls. 4. discussion currently, pfizer-biontech, moderna, and janssen vaccines are the main recommended choices for preventing sarscov-2 infection in pregnant women. this review aimed to describe the possible adverse outcome of covid-19 vaccines among pregnant women using the current evidence. eight of the included studies were cohort (61.5%), two were crosssectional, one was case report, and one was case-control. following pfizer-biontech and moderna vaccinations, the vast majority of pregnant women reported injection-site pain or soreness (16, 25-27). the most frequently experienced systemic adverse events were fatigue, headache, chills, myalgia, fever, and nausea (16, 25-29). the majority of pregnant women received their vaccine in the second trimester followed by the third trimester and first trimester, respectively (16, 21, 23, 26-28). the adverse events were not statistically different between vaccinated and unvaccinated pregnant women (29). serious adverse effects that impacted pregnancy, delivery, and neonatal outcomes were reported in some studies (16-18, 20, 21, 25, 27, 29), however; due to lack of information and the absence of a control group, we were not able to infer the causation or comment with certainty about the possible adverse outcomes. some studies reported no adverse events (22, 23) and found no significant difference between vaccinated and unvaccinated pregnant women (18). limited data are available on covid-19 vaccines’ efficacy and safety during pregnancy as almost all the vaccine trials excluded this population. pregnant women and their obstetricians can use available data to weigh the benefits and risks of covid-19 vaccines, even though they are limited. most available data come from animal studies and inadvertently exposed pregnant women during vaccine clinical trials and include data concerning the potential risks of vaccines during pregnancy due to vaccine reactogenicity, the timing of vaccination during pregnancy, evidence for the safety of other vaccines during pregnancy, risk of covid-19 complications in pregnancy among those with underlying conditions, risk of exposure to severe acute respiratory syndrome coronavirus 2 (sars-cov-2), and potential for risk mitigation (30). in our study, the majority of pregnant women were vaccinated in the second trimester or median gestational age. likewise; in zauche’s study, vaccinated pregnant participants were in the second trimester (27). additionally, in wainstock’s study, women who received the second dose vaccination were at a slightly higher gestational age (29). in the present review, no medical history or underlying disease was documented in most of the included articles. likewise, in trostle’s study, the majority of pregnant women had no prepregnancy comorbidities (24). in this review, the main local side effect was injection site pain, and the main systemic side effect was fever. other local and systemic side effects were rash, fever, severe fatigue, arthralgia, myalgia, headache, sore arm or pain, fatigue, chills, nausea, vomiting, etc. similarly, in gray’s study, injection site soreness and fever were the most reported side effects (17). in sukarno’s review study, fever, headache, pain, weakness, and arthralgia were common side effects of covid-19 vaccination in pregnant and lactating women (31). likewise, oriji’s study showed that the most common side effect was fever and pain at the injection site, but other side effects such as headache, tiredness, and chills were less frequent (32). in another observational study, injection site pain was the most common local side effect in healthcare workers, and fatigue, headache, muscle pain, and chills were the most common systemic side effects; however, fever was less common (33). fever with non-specific symptoms after covid19 vaccination may be due to a common tropical infection, especially if recovery from fever does not occur within 48 hours post-vaccination (34). the reason for the slight variation in the prevalence of complications could be the differences in study population, number of participants, comorbidities, physical conditions, the type of vaccine, and time of vaccination. few studies reported serious maternal adverse effects including itp, axillary adenopathy, vaginal bleeding, uterine contraction and convulsion (16, 25, 35-38). mild systemic side effects including fever, headache, and fatigue appeared to be similar to non-pregnant women. hospital admission was reported in one study, but only in 0.2% of cases (18). most studies have focused on fetus-related complications (16, 21, 23, 24). major congenital abnormality was rare (22, 23). pregnancy loss rarely occurred, except in a cohort study from the usa, which reported a relatively high percentage of pregnancy loss, about 13.9%, among 827 pregnant women (23). premature labor has been mentioned in three studies with an incidence of less than 10% (18, 23, 24). abortion was reported among 0.7% in one study (26) ,1.7% in another study (18) and 2.12% in another one (24); intrauterine growth restriction (iugr) was reported in 0.5% in one study (18) and 3.2% in another one (23) among pregnant women who received covid-19 vaccine during their pregnancy. the need for nicu admission was reported only in three studies (16, 21, 26). the reported rates in which were 0.5%, 2.4%, and 15.3%, respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 10 table 2: assessment of studies’ quality using the newcastle-ottawa scale (nos) the first author (reference) selection (out of 4) comparability (out of 2) exposure/outcome (out of 3) total score (out of 9) blakeway, h. (22) *** ** ** 7 carrie bennett (20) *** * ** 6 s. booksteinperetz(16) **** ** * 7 tom t. shimabukuro (23) *** ** *** 8 megan e trostle(24) *** ** ** 7 regan n. theiler (28) ** ** ** 6 tamar wainstock(29) ** * *** 6 lauren head zauche(27) *** ** *** 8 renukaananthkalyankadali(25) *** ** ** 7 kathryn j. gray (17) *** * ** 6 collier a-ry (21) **** ** ** 8 goldshtein i (18) *** * ** 6 kachikis a (39) *** ** *** 8 abraham b (35) *** ** ** 7 ben-mayor bashi t (37) *** * ** 6 arulappen al (36) *** ** ** 7 blakeway h (38) *** ** *** 8 peretz-machluf r (19) **** ** ** 8 toussia-cohen s (40) *** ** ** 7 moro pl (41) *** ** ** 7 5. research implication although larger studies and randomized controlled trials (rcts) are required to address long term and infrequent adverse events and possible side effects associated with covid19 vaccination, as well as the effect of vaccination at earlier stages of pregnancy, the current findings support the safety of the mrna vaccines considering pregnancy and delivery complications. furthermore, future studies with larger sample sizes, which include vaccine administration in each trimester and evaluation of fetal/neonatal immunoglobulin transfer via the umbilical cord and breast milk, may help us develop evidence-based recommendations for vaccine administration. 6. clinical implication policy-makers and healthcare professionals (hcps) should use this knowledge to strongly recommend and advise pregnant women to accept covid-19 vaccination and encourage them with the extending evidence that the covid-19 vaccines are safe and effective during pregnancy, considering the maternal morbidity associated with covid-19 during pregnancy. 7. limitations the novelty of the topic and scarcity of research concerning the possible side effects of covid-19 vaccine in pregnant women limited our ability to provide reliable evidence. besides, the study design of included studies did not allow for reliable causal inferences. it is also difficult to clinically randomize pregnant patients into diverse groups for vaccination and therefore, most of the trials excluded this vulnerable population from their study. thus, it is recommended for future studies to encourage pregnant women to participate to enable the decision-maker to determine the safety of the vaccine. 8. conclusion we found that similar to non-pregnant women, pregnant women could experience some local and systemic side effects with no significant difference. fever and chills, as the systemic side effects, along with local pain and redness, as the local side effects, were the most commonly reported symptoms in pregnant women who received the covid19 vaccine. there were also some reports of itp, adenopathy, vaginal bleeding, uttering contraction and convulsion in some pregnant women. some studies also reported abortion and premature labor in vaccinated pregnant women. however, these incidences could not certainly be attributed to the covid-19 vaccine’s adverse effects and more longitudinal and experimental studies are needed to define the exact adverse effects of the covid-19 vaccine in pregnant women. 9. declarations 9.1. acknowledgments the present study was conducted in collaboration with khalkhal university of medical sciences, iranian research this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e76 center for hiv/aids, tehran university of medical sciences, and bergen university. 9.2. authors’ contributions the conception and design of the study: esmaeil mehraeen, seyedahmad seyedalinaghi acquisition of data: mehrzad mohssenipour, solmaz saeidi analysis and interpretation of data: pedram habibi, mohsen dashti drafting the article: newsha nazarian, tayebeh noori, zahra pashaei, amirbehzad bagheri, afsaneh ghasemzadeh, amir masoud afsahi, narjes aghaie, paniz mojdeganlou, ghazal arjmand, ghazal zargari, roshanak modiri, hengameh mojdeganlou, armin razi revising it critically for important intellectual content: seyedahmad seyedalinaghi, omid dadras and esmaeil mehraeen final reading and approval of the version to be submitted: all authors 9.3. funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 9.4. competing interests the authors declare that there is no conflict of interest regarding the publication of this manuscript. 9.5. ethics approval and consent to participate not applicable 9.6. consent to publication not applicable 9.7. availability of data and material the authors stated that all information provided in this article could be share. references 1. dadras o, alinaghi sas, karimi a, mohssenipour m, barzegary a, vahedi f, et al. effects of covid-19 prevention procedures on other common infections: a systematic review. eur j med res. 2021;26(1):67. 2. mehraeen e, salehi ma, behnezhad f, moghaddam hr, seyedalinaghi s. transmission modes of covid19: a systematic review. infect disord drug targets. 2021;21(6):e170721187995. 3. mehraeen e, seyedalinaghi s, karimi a. can children of the sputnik v vaccine recipients become symptomatic? hum vaccin immunother. 2021;17(10):3500-1. 4. polack fp, thomas sj, kitchin n, absalon j, gurtman a, lockhart s, et al. safety and efficacy of the bnt162b2 mrna covid-19 vaccine. n engl j med. 2020;383(27):2603-15. 5. ramasamy mn, minassian am, ewer kj, flaxman al, folegatti pm, owens dr, et al. safety and immunogenicity of chadox1 ncov-19 vaccine administered in a prime-boost regimen in young and old adults (cov002): a single-blind, randomised, controlled, phase 2/3 trial. lancet. 2021;396(10267):1979-93. 6. shimabukuro t, nair n. allergic reactions including anaphylaxis after receipt of the first dose of pfizerbiontech covid-19 vaccine. jama. 2021;325(8):780-1. 7. dieleman j, romio s, johansen k, weibel d, bonhoeffer j, sturkenboom m. guillain-barre syndrome and adjuvanted pandemic influenza a (h1n1) 2009 vaccine: multinational case-control study in europe. bmj. 2011;343:d3908. 8. shah s, patel j, alchaki ar, eddin mf, souayah n. development of transverse myelitis after vaccination, a cdc/fda vaccine adverse event reporting system (vaers) study, 1985–2017. 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attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e76 40. toussia-cohen s, yinon y, peretz-machluf r, segal o, regev n, asraf k, et al. early adverse events and immune response following second and third covid-19 vaccination in pregnancy. j clin med. 2022;11(16):4720. 41. moro pl, olson ck, zhang b, marquez p, strid p. safety of booster doses of coronavirus disease 2019 (covid19) vaccine in pregnancy in the vaccine adverse event reporting system. obstet gynecol. 2022;140(3):421. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion research implication clinical implication limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e52 or i g i n a l re s e a rc h predicting the 28-day mortality of non-trauma patients using rems and raps; a prognostic accuracy study omid garkaz1, farzin rezazadeh2, saeed golfiroozi3, sahar paryab4, sadaf nasiri5, hamidreza mehryar6∗, mousa ghelichi-ghojogh7 1. school of public health, shahroud university of medical sciences, shahroud, iran. 2. emergency medicine department, urmia university of medical sciences, urmia, iran. 3. department of emergency medicine, school of medicine, golestan university of medical sciences, gorgan, iran. 4. school of nursing and midwifery, shahroud university of medical sciences, shahroud, iran. 5. urmia university of medical sciences, urmia, iran. 6. department of emergency medicine, school of medicine, urmia university of medical sciences, urmia, iran. 7. epidemiology department, golestan university of medical sciences, gorgan, iran. received: april 2022; accepted: may 2022; published online: 4 july 2022 abstract: introduction: various scoring systems have been designed for calculating the mortality risk of patients. this study evaluated the accuracy of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in predicting the 28-day mortality of non-trauma patients. methods: this prospective cross-sectional study was conducted on 1003 adult non-trauma patients, who referred to the emergency department of imam khomeini hospital, urmia, iran, in the second half of 2018, using the census sampling. we determined the screening performance characteristics of rems and raps in predicting the 28-day mortality of patients. results: this study examined 1003 non-trauma patients with a mean age of 61.5±18.05 years (60.6% male). the mean rems (8.7 ± 3.2 vs. 6.0 ± 3.6; p < 0.001) and raps (3.7 ± 2.8 vs. 2.7 ± 2.0; p < 0.001) scores were significantly higher in deceased cases. sensitivity and specificity of rems in predicting the risk of non-trauma patients’ mortality were 85.19% (95%ci: 78.05% 90.71%) and 78.34% (95%ci: 75.45% 81.04%), respectively. while, the sensitivity and specificity of raps in this regard were 61.39% (95%ci: 53.33% 69.02%) and 71.12% (95%ci: 67.94% 74.16%), respectively. the area under the receiver operating characteristic (roc) curve of rems and raps were 0.72 (95% ci: 0.68 -0.75) and 0.62 (95% ci: 0.56 0.65) in predicting the patients’ 28-day mortality, respectively (p = 0.001). conclusion: the total accuracies of rems and raps in predicting the 28-day mortality of non-trauma patients were in good and poor range, respectively. the screening performance characteristics of rems were a little better in this regard. keywords: emergencies; emergency service, hospital; mortality; clinical decision rules; prognosis cite this article as: garkaz o, rezazadeh f, golfiroozi s, paryab s, nasiri s, mehryar h, ghelichi-ghojogh m. predicting the 28-day mortality of non-trauma patients using rems and raps; a prognostic accuracy study. arch acad emerg med. 2022; 10(1): e52. https://doi.org/10.22037/aaem.v10i1.1601. 1. introduction various scoring systems have been designed for calculating the mortality risk of patients. these systems are methods designed to quantify the severity of the disease and the patient’s ∗corresponding author: hamidreza mehryar; resalat boulevard, emergency alley, urmia, iran. postal address: 5714783734, email: hamidrezamehryar2010@gmail.com, orcid: http://orcid.org/0000-0002-3267-8647. condition by integrating the various properties affecting it (1, 2). several scoring systems have been proposed to assess disease severity in recent decades (3, 4). they are mainly used in critically ill patients and their common goal is to measure deviations in various physiological variables to provide an objective measure of the severity of the disease known to physicians worldwide. a wide range of applications of the tools envisioned by hazy are described (5). classifying the severity of illness in the emergency department (ed), along with an acthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. garkaz et al. 2 curate history of the disease, can classify critically ill patients. scoring systems can also be used to evaluate the use of hospital resources and compare different emergency departments in shortand long-term. scoring systems could also be a potential triage tool for emergency nurses. one of these scoring systems is acute physiology and chronic health evaluation ii )apacheii(, , described by knaus et al., which classifies the severity of disease (6). however, the apache ii score contains several blood chemical variables and is, therefore, not suitable for rapid assessment in the emergency department. rapid acute physiology score (raps) is a summary of apache ii, which was initially used as a hospital scoring system for the patients transported by helicopter (7). an important advantage of raps is the simplicity of its assessment method. rapid emergency medicine score (rems) is an attenuated version of apache ii score and can predict mortality in nonsurgical patients (8). a study on performance of rems in predicting the in-hospital mortality of trauma patients confirmed its simplicity and accuracy in this regard (9). due to the limited number of variables in the raps and rems, it is possible to evaluate and calculate scores based on these models and easily use them in ed. however, only a few studies have compared the two models (7, 10, 11), and there are still controversies over their use in evaluating the mortality of non-trauma patients. given this, we intended to evaluate the accuracy of rems and raps in predicting the 28-day mortality of non-trauma patients. 2. methods 2.1. study design and setting this descriptive cross-sectional study was conducted on 1003 non-trauma patients, who referred to the emergency department of imam khomeini hospital, urmia, iran, in the second half of 2018, using census method. we determined the screening performance characteristics of rems and raps in predicting the 28-day mortality of adult nontrauma patients. this study was registered in urmia university of medical sciences with the ethics code of ir.umsu.rec.1397.213. while following the patients, we explained the research plan to them and ensured their willingness to participate in the study. the participants were assured that their information would be kept confidential. 2.2. participants in this study, adult non-trauma patients with complete patient files were included. we excluded patients who had died before reaching the ed. 2.3. data collection procedures a predesigned checklist that included information about patients’ age, gender, and final outcome (deceased or discharged), and the rems and raps was filled out for all patients using their profiles. rems variables included age, level of consciousness, mean blood pressure, respiration rate, and oxygen level; and the raps consisted of pulse rate, blood pressure, respiration rate, and glasgow coma scale (gcs) score (appendix 1 and 2). all the information was recorded upon patients’ arrival at the emergency department and patients were also contacted for a 28-day follow-up of death or recovery. an emergency physician was responsible for data gathering. 2.4. statistical analysis the data were analyzed using spss18, and the findings were reported using descriptive statistics (mean ± standard deviation) or frequency (%). the screening performance characteristics of rems and raps in predicting the 28-day mortality of non-trauma patients were calculated using a calculator (http://vassarstats.net/clin1.html) and the area under the receiver operating characteristic (roc) curve. the analysis results were reported with 95% confidence interval (ci). 3. results this study examined 1003 non-trauma patients with a mean age of 61.5±18.05 years (60.6% male). table 1 compares the baseline characteristics and rems and raps between deceased and discharged patients. the mean rems (8.7 ± 3.2 vs. 6.0 ± 3.6; p < 0.001) and raps (3.7 ± 2.8 vs. 2.7 ± 2.0; p < 0.001) scores were significantly higher in deceased cases. table 2 shows the screening performance characteristics of rems and raps in predicting the risk of 28-day mortality in non-trauma patients. sensitivity and specificity of rems in predicting the risk of in hospital mortality of non-trauma patients were 85.19% (95%ci: 78.05% 90.71%) and 78.34% (95%ci: 75.45% 81.04%), respectively. while, the sensitivity and specificity of raps in this regard were 61.39% (95%ci: 53.33% 69.02%) and 71.12% (95%ci: 67.94% 74.16%), respectively. the area under the roc curve of rems and raps was 0.72 (95% ci: 0.68 -0.75) and 0.62 (95% ci: 0.56 0.65), respectively, (figure 1; p = 0.001) in predicting the 28-day mortality. 4. discussion based on the findings of the present study, it seems that rems is a better predictor of the 28-day mortality of nontrauma patients in emergency department compared to raps. in this study, there was a significant difference between the two groups (discharged and deceased patients) in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e52 terms of mean rems. the mean rems of deceased patients was higher compared to that of discharged patients. there was also a significant difference between the two groups (discharged and deceased patients) regarding the mean raps. the mean raps of deceased patients was higher than that of discharged patients. in a similar study, seak et al. (12) evaluated the performance of rems in predicting in-hospital mortality in non-surgical emergency department patients. in their study, rems was a powerful predictor of in-hospital mortality in patients admitted to the emergency department with a wide range of common internal disorders. the results of that study were similar to our study. in a study by ha et al. (13), on predicting the prognosis of patients based on rems and the worthing physiological assessment system (wps) in the emergency department, both rems and wps had a good performance in predicting death in critically ill patients. in similar studies, plunkett et al. (14) and nakhchivan et al. (7) showed that rems is a better predictor of mortality at the time of admission of inpatients compared to raps. the results of these studies are consistent with our study. rems seems to be a powerful predictor of in-hospital mortality among patients referring to the emergency department with a wide range of common internal disorders. one of the laboratory scoring methods was described based on biochemistry tests on admission, which identified high-risk patients for in-hospital death. risk profiles on admission could be a means of improving outcomes (15). identifying high-risk patients can be the basis for purposeful intervention after emergency medical care. this study confirms that the rems has better discriminatory power than the raps regarding inhospital mortality. olson et al. used similar methods to calculate rems and evaluate the predictive power of raps. they found that rems was a better predictor of nosocomial mortality compared to raps (16). in our study, the accuracy of rems in prediction of mortality was 72.2%, this rate was 62.6% for raps based on the area under the roc curve (auroc). sensitivity of rems (72.2%) was higher than the sensitivity of raps (62.6%). the cut-off points for rems and raps criteria were 6.5 and 2.5, respectively. according to the linear regression model, it can be concluded that age, map, hr, respiratory rate (rr), spo2, and gcs (54.7%) could predict the rems criterion. olsson’s estimation of auroc for raps (0.65) was very similar to ours (0.56 0.65), though their estimation of auroc for rems (0.85) was significantly higher (0.68 0.75). bahrmann et al. (17) found that all six components of rems were associated with hospital mortality, while the relationship between mean arterial pressure and mortality was not significant in multivariate analysis. our findings and results clearly suggest that blood pressure is not a good predictor of mortality. in contrast to our study, heart rate and respiration were independent predictors of mortality in their study. 5. limitations the study was performed in a single center and thus, the results may not be generalizable. further studies need to be carried out to validate the rems and determine whether heart rate and respiratory rate are independent predictors of mortality. ideally, risk classification tools for emergency care should be developed through pilot studies to identify all potentially useful variables and find variables having independent relationships with outcome, extract scores, and validate them in a different population. it should be noted that a risk classification tool that is useful for predicting death may not be useful for triage or clinical practice. predicting mortality in triage or clinical practice may require distinguishing between avoidable and unavoidable mortality. 6. conclusion it seems that rems is a better predictor of the 28-day mortality of non-trauma patients in an emergency department compared to raps. it should be noted that the total accuracy of rems and raps in this regard was in good and poor range, respectively. 7. declarations 7.1. acknowledgments the researchers are grateful for the support of urmia university of medical sciences, the medical records staff of imam khomeini hospital in urmia, the deputy minister of development and technology, and all those who cooperated with us in doing this research. 7.2. financial resources this study was financially supported by the vice chancellor for research and technology of urmia university of medical sciences. 7.3. authors’ contributions omid garkaz (first author), was a statistical analyst (10%), farzin rezazadeh (second author), author of the article (15%), saeed golfiroozi (third author) author of the introduction (%10), sahar paryab (fourth author) author of the discussion (20%), sadaf nasiri, lead researcher/ (fifth author) (10%), hamid reza mehryar (sixth author), assistant researcher (25%), and mousa ghelichi-ghojogh (seventh author) author of methodology (%10). the last version of manuscript was read and approved by all authors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. garkaz et al. 4 7.4. conflict of interest the authors declare that there is no conflict of interest regarding the publication of this article. references 1. oliveira vmd, brauner js, rodrigues filho e, susin rg, draghetti v, bolzan st, et al. is saps 3 better than apache ii at predicting mortality in critically ill transplant patients? clin. sci. 2013;68(2):153-8. 2. villeneuve a, joyal j-s, proulx f, ducruet t, poitras n, lacroix j. multiple organ dysfunction syndrome in critically ill children: clinical value of two lists of diagnostic criteria. ann. intensive care. 2016;6(1):1-7. 3. knaus wa, draper ea, wagner dp, zimmerman je. apache ii: a severity of disease classification system. crit care med. 1985;13(10):818-29. 4. garkaz o, mehryar hr, khalkhali hr, salari lak s. factors affecting the severity of traffic accident injuries; a cross-sectional study based on the haddon matrix. trauma mon. 2020;25(1):52-8 5. hyzy rc. icu scoring and clinical decision making. chest. 1995;107(6):1482-3. 6. knaus wa, draper ea, wagner dp, zimmerman je. apache ii-a severity of disease classification system: reply. crit care med. 1986;14(8):755-802. 7. nakhjavan-shahraki b, baikpour m, yousefifard m, nikseresht zs, abiri s, razaz jm, et al. rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative study. arch. acad. emerg. med. 2017;5(1).1-8 8. nakhjavan-shahraki b, yousefifard m, faridaalaee g, shahsavari k, oraii a, hajighanbari mj, et al. performance of physiology scoring systems in prediction of inhospital mortality of traumatic children: a prospective observational study. j clin orthop trauma. 2017;8(2):438. 9. imhoff bf, thompson nj, hastings ma, nazir n, moncure m, cannon cm. rapid emergency medicine score (rems) in the trauma population: a retrospective study. bmj open. 2014;4(5):e004738. 10. toloui a, neishaboori am, alavi snr, gubari mi, khaneh azs, ghahfarokhi mk, et al. the value of physiological scoring criteria in predicting the in-hospital mortality of acute patients; a systematic review and meta-analysis. arch. acad. emerg. med. 2021;9(1).e60 11. hilderink mj, roest aa, hermans m, keulemans yc, stehouwer cd, stassen pm. predictive accuracy and feasibility of risk stratification scores for 28-day mortality of patients with sepsis in an emergency department. eur j emerg med. 2015;22(5):331-7. 12. seak c-j, yen dh-t, ng c-j, wong y-c, hsu k-h, seak jcy, et al. rapid emergency medicine score: a novel prognostic tool for predicting the outcomes of adult patients with hepatic portal venous gas in the emergency department. plos one. 2017;12(9):e0184813. 13. ha dt, dang tq, tran nv, vo ny, nguyen nd, nguyen tv. prognostic performance of the rapid emergency medicine score (rems) and worthing physiological scoring system (wps) in emergency department. int j emerg med. 2015;8(1):1-8. 14. plunkett pk, byrne dg, breslin t, bennett k, silke b. increasing wait times predict increasing mortality for emergency medical admissions. eur j emerg med. 2011;18(4):192-6. 15. conway r, byrne d, o’riordan d, silke b. patient risk profiling in acute medicine: the way forward? qjm: int. j. medical sci. 2015;108(9):689-96. 16. olsson t, terent a, lind l. charlson comorbidity index can add prognostic information to rapid emergency medicine score as a predictor of long-term mortality. eur j emerg med. 2005;12(5):220-4. 17. bahrmann a, benner l, christ m, bertsch t, sieber cc, katus h, et al. the charlson comorbidity and barthel index predict length of hospital stay, mortality, cardiovascular mortality and rehospitalization in unselected older patients admitted to the emergency department. aging clin exp res. 2019;31(9):1233-42. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e52 figure 1: area under the receiver operating characteristic (roc) curve of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in predicting the risk of in-hospital mortality of non-trauma patients in emergency department (p = 0.001). appendix 1: rapid emergency medicine score (rems) variable score 0 1 2 3 4 5 6 age (year) <45 45-54 55-64 65-74 >74 emergency score 70-109 110-129 50-69 130-159 >159 ≤49 heart rate (/minutes) 70-109 110-139 55-69 140-179 40-54 179 ≤39 respiratory rate (/minutes) 12-24 25-34 1011 6-9 35-49 >49 ≤5 spo2 (%) >89 86-89 75-85 <75 gcs 14 or 15 11-13 8-10 5-7 3 or 4 gcs: glasgow coma scale; sao2: oxygen saturation. appendix 2: rapid emergency medicine score (raps) variable points +4 +3 +2 +1 0 +1 +2 +3 +4 map 160≥ 130-159 110-129 70-109 50-69 49≤ hr 180≥ 140-179 110-139 70-109 55-69 40-54 39≤ resp* 50≥ 35-49 25-34 12-24 10-11 6-9 5≤ gcs 14≥ 11-13 10-8 5-7 4≤ map: mean arterial pressure; hr: heart rate; resp: respirations; gcs: glasgow coma scale. score of 0 is normal. *spontaneous or, if not spontaneous, ventilated rate. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. garkaz et al. 6 table 1: comparing the baseline characteristics as well as rapid emergency medicine score (rems) and rapid acute physiology score (raps) of studied cases between survived and non-survived cases variable outcome p value deceased discharged age (year) mean ± sd 66.5±13.9 56.5 ± 22.2 < 0.001 gender male 427(70.2) 181(29.8) < 0.001 female 330(83.6) 65(16.4) vital signs sbp (mmhg) 112.9 ± 31.4 125.5 ± 27.7 <0.001 dbp (mmhg) 69.5 ± 20.0 79.0 ± 20.8 <0.001 map (mmhg) 84.1 ± 22.8 94.7 ± 21.7 <0.001 hr (/minute) 101.1 ± 25.8 92.2 ± 22.2 <0.001 sao2 (%) 91.9 ± 15.1 92.0 ± 7.3 <0.001 rr (/minute) 18.0 ± 2.9 21.1 ± 3.5 <0.001 gcs 8.1 ± 2.2 9.9 ± 2.2 <0.001 predicting models rems 8.7 ± 3.2 6.0 ± 3.6 <0.001 raps 3.7 ± 2.8 2.7 ± 2.0 <0.001 data are presented as mean ± standard deviation (sd) or frequency (%). sbp: systolic blood pressure; dbp: diastolic blood pressure; map: mean arterial pressures; hr: heart rate; sao2: oxygen saturation; rr: respiratory rate. gcs: glasgow coma scale. table 2: screening performance characteristics of rapid emergency medicine score (rems) (cut-off = 6.5) and rapid acute physiology score (raps) (cut-off = 2.5) in predicting the risk of in-hospital mortality among non-trauma patients character rems (95%ci) raps (95%ci) true positive 115 97 true negative 680 601 false positive 188 244 false negative 20 61 sensitivity 85.19(78.05-90.71) 61.39(53.33-69.02) specificity 78.34(75.45-81.04) 71.12(67.94-74.16) positive predictive value 37.95(34.61-41.42) 97.58(97.17-97.94) negative predictive value 97.14(95.77-98.08) 8.84(7.35-10.60) positive likelihood ratio 3.93(3.40-4.55) 2.13(1.81-2.50) negative likelihood ratio 0.19(0.13-0.28) 0.54(0.44-0.66) accuracy 79.26(70.37-84.25) 61.88(58.79-64.90) ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e18 editorial an overview of published articles in archives of academic emergency medicine in 2021 mehrnoosh yazdanbakhsh1, somayeh saghaei dehkordi1∗ 1. journal office, emergency ward, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: february 2021; accepted: february 2021; published online: 27 february 2022 cite this article as: yazdanbakhsh m, saghaei dehkordi s. an overview of published articles in archives of academic emergency medicine in 2021. arch acad emerg med. 2022; 10(1): e18. https://doi.org/10.22037/aaem.v10i1.1555. archives of academic emergency medicine has published 70 articles in 2021, which have been authored by more than three hundred researchers from various countries, including but not limited to the united states, australia, india, japan, thailand, iraq, pakistan, france, greece, and iran. in this editorial, we intend to provide an overview of our publications in 2021, so that we can identify our strengths and weaknesses and provide a brief report on our performance to readers and authors, which they might find useful in becoming more familiar with the journal. just like the previous year, the published papers are indexed in scopus, web of sciences, pubmed, and some other databases specified on the journal’s website. however, the scopus citescore for the journal improved from 2.4 in 2020 to 4.5 in 2021 (https://www.scopus. com/sourceid/21101017909?origin=resultslist). the acceptance rate has been 18.81% in 2021 and reaching the decision to accept the articles has taken an average of 54 days. out of the 70 published papers, 41 (58.57%) were original articles, 14 (20.0%) were review articles, 8 (11.42%) were case reports, and 7 (10.0%) were letters to editor. all published articles were matching the emergency medicine scope and were in line with journal commitments. since the covid-19 pandemic was still an issue throughout 2021 and there were still unknown aspects about this disease, researchers wanted to report new findings of the disease and its patterns and consequences, as well as its management. thus, by publishing studies in this field, we tried our best to make these insights available to all health care providers around the world. so that they could learn from the experiences of each other and become more equipped to face the disease efficiently and make the lives of ∗corresponding author: somayeh saghaei dehkordi; emergency ward, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. email: ma.saghaei63@gmail.com, tel: 0982122721155. those affected by the disease in any way easier during these difficult times. twenty-one (30.0%) of the published articles were related to covid-19. eleven articles were original research papers (1-11), 3 articles were letters (12-14), 2 were case reports (15, 16), and five articles were review studies (17-20). the 49 remaining articles, which consisted of 30 original articles, 9 review articles, 6 case reports, and 4 letters were on different topics. the letters consisted of 2 reports of preliminary studies performed (21, 22) and 2 expert views on different matters (23, 24). the letters are always reviewed by the editor and they are reviewed by external reviewers in case of presenting the findings of a study. among the case reports, 1 was on possible complications arising after treatments (25) and 5 reported unusual presentations of diseases (26-30). these reports were published to raise other physicians’ awareness of those situations so that they can either prevent facing the same situation or be able to better manage the situation if they encounter it. only one of the review articles was a narrative one (31) and the rest were systematic reviews and/or meta-analyses. systematic reviews and meta-analyses are ranked as the highest level of evidence among articles and may be able to provide an answer to a burning question (32-38). therefore, it is not surprising to see that 7.14% of this year’s review articles were related to covid-19. in this journal, we aim to introduce novel electronic approaches helping the management of patients. machine learning is one of the novel fields in medicine, which may transform the practice of medicine, in 2021 we published 2 articles in that field (39, 40). our aim in this journal is to play a part, even if it is a small one, in helping physicians do their practice of medicine, which can consequently improve the general health of all societies. this will not be possible without the hard work of researchers who perform the studies, so we would like to thank all the authors who trusted us with their valuable this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yazdanbakhsh and s. saghaei dehkordi 2 works throughout 2021. our goal is to keep improving and continue to publish quality articles by authors from all over the world and everybody is invited to join us. references 1. saberian p, mireskandari sm, baratloo a, hasanisharamin p, babaniamansour s, aliniagerdroudbari e, et al. antibody rapid test results in emergency medical services personnel during covid-19 pandemic; a cross sectional study. archives of academic emergency medicine. 2021;9(1):e2. 2. pishgahi m, karimi toudeshki k, safari s, yousefifard m. echocardiographic abnormalities as independent prognostic factors of in-hospital mortality among covid19 patients. archives of academic emergency medicine. 2021;9(1):e21. 3. saberian p, rafiemanesh h, sadeghi m, hasani-sharamin p, dadashi f, baratloo a. the geographical distribution of probable covid-19 patients transferred by tehran emergency medical services; a cross sectional study. archives of academic emergency medicine. 2021;9(1):e25. 4. rezaei-tavirani m, rostami nejad m, arjmand b, rezaei tavirani s, razzaghi m, mansouri v. fibrinogen dysregulation is a prominent process 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in management of myocarditis associated with covid-19; a systematic review of current evidence. archives of academic emergency medicine. 2021;9(1):e32. 21. ali s, zahid a, jamal sz, khan st, lohana n, ahmed r, et al. cardiologists’ knowledge and perception towards american heart association guidelines of cardiopulmonary resuscitation; a letter to editor. archives of academic emergency medicine. 2021;9(1):e11. 22. zeinali.n f, mohammad karimi n, jafari m, akbarzadeh moghadam e. rapid and deep versus normal breathing in salbutamol inhalation effectiveness; a letter to editor: comparison of 2 inhalation methods efficacy. archives of academic emergency medicine. 2021;9(1):e42. 23. vlastarakos p, chondrogiannis k. video-laryngoscopyassisted fishbone removal from the upper digestive tract; a letter to the editor: video-laryngoscopy assisted fishbone removal. archives of academic emergency medicine. 2021;9(1):e12. 24. rezvani kakhki b, miri m, talebi doluee m, sabeti baygi z, abbasi shaye z, vafadar moradi e. tactile method in confirming proper endotracheal intubation in emergency setting; a letter to editor: confirm intubation. archives of academic emergency medicine. 2021;9(1):e38. 25. mirkarimi t, salek m, modirian e, namdar p. delayed post-traumatic tension hydropneumocephalus; a case report of conservative treatment. archives of academic emergency medicine. 2021;9(1):e22. 26. nojima t, naito h, obara t, tsukahara k, nakao a. plastic bronchitis in a five-year-old boy treated using extracorporeal membrane oxygenation; a case report. archives of academic emergency medicine. 2021;9(1):e16. 27. rasras h, beghi m, samti m, ismaili n, el ouafi n. rare and underestimated association of pulmonary embolism and olanzapine therapy; report of two cases: pulmonary embolism and olanzapine therapy. archives of academic emergency medicine. 2021;9(1):e17. 28. banavathu t, tripathi s, sukhadiya p, ahari k, meena ds, garg mk. thyrotoxic periodic paralysis with thyroid storm as the first presentation of graves’ disease; a case report. archives of academic emergency medicine. 2021;9(1):e19. 29. najari f, malekpour-alamdari n, baradaran kial i, najari d, mirzaei s. prolonged fever; a case report of medical malpractice. archives of academic emergency medicine. 2021;9(1):e49. 30. mehdi z, bhardwaj n, aggarwal j, kaur n, singh b. facial nerve palsy with total ophthalmoplegia; a novel presentation of fungal invasion. archives of academic emergency medicine. 2021;9(1):e54. 31. heidari beigvand h, heidari k, hashemi b, saberinia a. the value of lactate dehydrogenase in predicting rhabdomyolysis-induced acute renal failure; a narrative review. archives of academic emergency medicine. 2021;9(1):e24. 32. shaterian n, abdi f, atarodi kashani z, shaterian n, darvishmotevalli m. facemask and respirator in reducing the spread of respiratory viruses; a systematic review. archives of academic emergency medicine. 2021;9(1):e56. 33. yousefifard m, madani neishaboori a, rafiei alavi sn, 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distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem references archives of academic emergency medicine. 2022; 10(1): e49 or i g i n a l re s e a rc h clinical and laboratory predictors of covid-19-related in-hospital mortality; a cross-sectional study of 1000 cases zohreh mohammadi1, masood faghih dinevari2, nafiseh vahed3, haniyeh ebrahimi bakhtavar1, farzad rahmani4∗ 1. emergency and trauma care research center, tabriz university of medical sciences, tabriz, iran. 2. liver and gastrointestinal diseases research center, tabriz university of medical sciences, tabriz, iran. 3. research center for evidence-based medicine, tabriz university of medical sciences, tabriz, iran. 4. road traffic injury research center, tabriz university of medical sciences, tabriz, ir iran. received: april 2022; accepted: may 2022; published online: 23 june 2022 abstract: introduction: identifying patients at risk for mortality and using appropriate treatment for each patient based on their situation could be an effective strategy in improving their outcome. this study aimed to evaluated the predictors of covid-19 in-hospital mortality. methods: this descriptive cross-sectional study was conducted on all adult covid-19 patients who were managed in imam-reza and sina hospitals, tabriz, iran, from november 2020 until december 2021. the demographic, clinical, and laboratory characteristics of patients were evaluated and predictors of in-hospital mortality were identified using logistic regression model. results: 1000 patients with the mean age of 56.34 ± 18.00 years were studied (65.7% male). there were significant associations between covid-19 in-hospital mortality and hospitalization above five days (p = 0.001), white blood cell count (wbc) > 4000 cells*103/ml (p < 0.01), aspartate aminotransferase (ast) above 40 iu/l (p = 0.001), alanine transaminase (alt) above 40 iu/l (p = 0.001), creatinine above 1.4 mg/dl (p = 0.007), urea above 100 mg/dl (p = 0.024), and sao2 below 80% (p = 0.001). hospital stay above five days (or: 3.473; 95%ci: 1.272 9.479; p = 0.15), ast above 40 iu/l (or: 0.269, 95%ci: 0.179 0.402; p = 0.001), creatinine above 1.4 mg/dl (or: 0.529; 95%ci: 0.344 0.813; p = 0.004), urea above 100 mg/dl (or: 0.327, 95%ci: 0.189 0.567; p = 0.001), and sao2 below 80% (or: 8.754, 95%ci: 5.413 14.156; p = 0.001) were among the independent predictors of covid-19 in-hospital mortality. conclusion: the mortality rate of patients with covid-19 in our study was 29.9%. hospitalization of more than five days, ast above 40 iu/l, creatinine above 1.4 mg/dl, urea above 100 mg/dl and sao2 < 80% were independent risk factors of in-hospital mortality among patients with covid-19. keywords: covid-19; mortality; prognosis; respiratory distress syndrome cite this article as: mohammadi z, faghih dinevari mf, vahed n, ebrahimi bakhtavar h, rahmani f. clinical and laboratory predictors of covid-19-related in-hospital mortality; a cross-sectional study of 1000 cases. arch acad emerg med. 2022; 10(1): e49. https://doi.org/10.22037/aaem.v10i1.1574. 1. introduction in december 2019, patients were diagnosed with pneumonia of unknown origin, later known as sars-cov-2 virus (severe acute respiratory syndrome coronavirus 2), in wuhan, china (1, 2). the clinical manifestation of sars-cov-2 infection is ∗corresponding author: farzad rahmani; emam reza medical research and training hospital, tabriz university of medical sciences, tabriz, iran. tel: 00984133352078, fax: 00984133352078, email: rahmanif@tbzmed.ac.ir, orcid: http://orcid.org/0000-0001-5582-9156. mutable and includes asymptomatic disease, upper respiratory tract disorders, and in some cases, acute and severe fatal conditions. therefore, to summarize the clinical manifestations and widespread consequences of sars-cov-2 infections, the who chose the specific name covid-19 (coronavirus disease 2019) for this disease (3-5). the mortality rate is the most crucial factor in turning an infection into a public concern and the risk of developing a pandemic. different viruses become epidemics each year, but very few of them become a public concern (6-8). swine influenza a (h1n1 virus), severe acute respiratory syndrome this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mohammadi et al. 2 (sars), and ebola (zaire ebolavirus) have led to global concern in recent years due to high mortality (9, 10). as in the above cases, covid-19 has received all the attention and has caused concern due to its high mortality rate (3, 11). for example, although the flu is widespread, its mortality rate is only 0.1%. reports have also shown that covid-19 is highly contagious and can spread via various routes (3, 5, 12). the rate of infectivity is a significant factor, but the mortality rate from covid-19 is not correctly estimated. because when the initial mortality rate is reported, only patients with very severe condition are in the statistical population, and patients with mild to moderate disease are not included in the investigation (12). the rapid development of covid-19 in wuhan, china, has resulted in thousands of deaths (13), and the widespread virus worldwide has resulted in hundreds of thousands of patients (14). in iran, who reports that there were about 10000 new cases of covid-19 per day during the study, and death rate was about 400 cases daily (15). more deaths were observed in patients with severe disease, and other patients in whom the disease symptoms were flulike, improved quickly, and returned to everyday life (5). in addition, the difference between the clinical features of patients with severe and non-severe diseases has been rarely reported (16, 17). also, in some studies, the clinical features of patients with severe diseases who died were compared with patients who survived after the infection. we hypothesized that assessing routine parameters such as vital signs and laboratory tests in covid-19 patients, especially patients with severe disease, can help medical staff better manage patients. therefore, this study aimed to design a predictive model of mortality in patients admitted with covid-19, to identify patients with different conditions and use appropriate treatment for each patient based on their situation. 2. methods 2.1. study design and setting this descriptive cross-sectional study was conducted with the approval of the institutional ethics committee at tabriz university of medical sciences (ir.tbzmed.rec.1399.950) in two medical research, training and treatment general hospitals, imam-reza and sina hospitals, tabriz, iran, from november 2020 until december 2021. the data of all adult covid-19 patients admitted in the mentioned hospitals during the study period were evaluated and predictors of inhospital mortality were determined using logistic regression model. 2.2. participants the study included patients older than 18 years, with covid-19 pneumonia, confirmed by reverse transcriptasepolymerase chain reaction (rt-pcr) for sars-cov-2. the figure 1: study flow diagram of patients’ enrolment. sampling method was a complete census. the minimum number of samples is 1000 patients. the sample size was estimated based on the covid-19 prevalence of 33% (18), a confidence interval of 95%, and a relative estimation error of 10%. exclusion criteria were incomplete information recorded in the patient’s medical record, discharge against medical advice, leaving the study in the middle of the study procedure, not willing to participate in the project, and negative pcr test (figure 1). 2.3. data gathering patients’ demographic characteristics at the time of admission (age, sex, body mass index (bmi)), underlying disease, drug history, vital signs (blood pressure, heart rate (hr), respiration rate (rr), body temperature, o2 saturation, avpu level of consciousness), need for supplemental oxygen (via nasal cannula or mask), lung involvement on computed tomography (ct) scan, and the laboratory test results were recorded in the checklist. laboratory findings included complete blood count (white blood cell (wbc), neutrophil, lymphocyte, hemoglobin and platelet counts), liver functional enzymes (including aspartate transaminase, alanine transaminase, and alkaline phosphatase), creatinine, urea, coagulation status (including prothrombin time (pt), partial thromboplastin time (ptt), and international normalized ratio (inr)), venous blood gas analysis (including ph, paco2, and hco3), and serum sodium (na) and potassium (k) status. the patients were followed up during hospitalization (short-term follow-up of 30 days), and the duration this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e49 figure 2: area under the receiver operating characteristic (roc) curve of hospital stay above five days (p value: 0.435), aspartate aminotransferase (ast) above 40 iu/l (p value: 0.001), creatinine above 1.4 mg/dl (p value: 0.001), urea above 100 mg/dl (p value: 0.001), and sao2 below 80% (p value: 0.001) in predicting the in-hospital mortality of covid-19 patients. of hospitalization, intubation, intensive care unit (icu) hospitalization, and outcome, including death or survival, were assessed. 2.4. outcome the study’s primary outcome was patient mortality during the hospitalization period or within 30 days from admission. 2.5. statistical analysis all data were entered into the spss 21. normal data distribution was assessed using kolmogorov-smirnov test. for the descriptive data, mean ± standard deviation was used to report the findings in the case of normal data distribution. in case of non-normal data distribution, the median was used, and for qualitative variables frequency (percentage) was reported. the independent sample’s t-test was used to compare quantitative data if the data distribution was normal, and the mann whitney u test was used if it was non-normal. the chi-square test was used to compare qualitative data. the receiver operating characteristic (roc) curve was used to determine the predictive value of each of the studied variables. area under the roc curve (auc), cut-off point, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios, and j point were reported. in all cases, a p value less than 0.05 was considered significant. logistic regression and odds ratio were used to determine the value of each variable and their coefficients to create the model. the primary bias of the study was missing data, to address this problem we excluded patients with missing data. the comparison was made between patients who survived and those who died. 3. results 3.1. baseline and clinical findings 1000 patients with the mean age of 56.34 ± 18.00 (range: 18 96) years were studied (65.7% male). the most frequent underlying disease was hypertension (32.2%). of all patients, 29.9% died during admission. the demographic and clinical findings of the studied patients are compared between survived and non-survived cases in table 1. results showed that the mean age of dead patients was significantly higher (59.36 ± 18.40 vs. 55.05 ± 17.68 years; p = 0.001), and the rate of mortality was significantly lower in females than in males this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mohammadi et al. 4 table 1: comparing the demographic and clinical findings between survived and non-survived cases variable alive (n=701) dead (n=299) dead (n=1000) p age (year) mean ± sd 55.05±17.68 59.36±18.40 56.34±18.00 0.001 sex male 443 (63.2) 214 (71.6) 657 (65.7) 0.011 female 258 (36.8) 85 (28.4) 343 (34.3) underlying disease htn 233 (33.2) 89 (29.8) 322 (32.2) 0.198 dm 92 (13.1) 40 (13.4) 132 (13.2) 0.212 hlp 11 (1.6) 6 (2.0) 17 (1.7) 0.134 hypothyroidism 14 (2.0) 9 (3.0) 23 (2.3) 0.313 cad 6 (0.9) 0 00.0) 6 (0.6) 0.219 cva 4 (0.6) 5 (1.7) 9 (0.9) 0.192 crf 16 (2.3) 9 (3.0) 25 (2.5) 0.217 vital signs hr (beats/min) 91.41±13.41 94.61±13.93 92.37±13.64 0.001 rr (breath/min) 22.05±9.79 23.28±8.67 22.42±9.48 0.031 bt 37.24±0.53 37.31±0.56 37.26±0.54 0.030 sbp (mmhg) 119.82±15.21 121.46±22.96 120.31±17.89 0.128 dbp (mmhg) 74.79±9.04 75.39±12.16 74.97±10.007 0.225 spo2 (%) 90.32±4.77 84.41±8.17 88.55±6.57 0.001 hospitalization (day) mean ± sd 5.52±4.19 6.23±5.00 5.73±4.45 0.016 * data were analyzed using independent-sample t test and chi-square and presented as mean ± standard deviation (sd) and frequency (%). ** htn: hypertension; dm: diabetes mellitus; hlp: hyperlipidemia; cad: coronary artery disease; cva: cerebrovascular accident; crf: chronic renal disease; hr: heart rate; rr: respiratory rate; bt: body temperature; sbp: systolic blood pressure; dbp: diastolic blood pressure. (28.4% vs. 71.6%; p = 0.011). the mean hr (94.61±13.93 vs. 91.41±13.41/minute; p = 0.001), rr (23.28 ± 8.67 vs. 22.05 ± 9.79/minute; p = 0.031), and temperature (37.31 ± 0.56 vs. 37.4 ± 0.53 celsius; p = 0.001) were significantly higher in dead patients; however, the value of sao2 (84.41±8.17 vs. 90.3±4.77%; p=0.001) was lower in dead cases. the length of hospitalization in dead patients was significantly longer (6.23 ± 5.00 vs. 5.52 ± 4.19 days; p=0.016). 3.2. laboratory findings laboratory and paraclinical findings of the patients are shown in table 2. the results showed that the values of wbc (8.27±7.71 vs. 7.53±5.29 cells*103; p = 0.009), neutrophils (81.68±9.90% vs. 78.93±12.19%; p=0.001), alt (60.82±66.04 vs. 46.11±47.48 iu/l; p=0.001), ast (56.46±75.00 vs. 41.73±38.55 iu/l; p=0.001), creatinine (1.56±1.34 vs. 1.23±12.1 mg/dl; p=0.001), and urea (62.85±54.98 vs. 42.98±32.62; p=0.001) were significantly higher in dead patients. 3.3. predictors of mortality there were significant associations between covid-19 inhospital mortality and hospitalization above five days (p = 0.001), wbc > 4000 cells*103/ml (p < 0.01), ast above 40 iu/l (p = 0.001), alt above 40 iu/l (p = 0.001), creatinine above 1.4 mg/dl (p = 0.007), urea above 100 mg/dl (p = 0.024), and sao2 below 80% (p = 0.001) (table 3). based on the results of multivariate logistic regression analysis, hospital stay above five days (or: 3.473; 95%ci: 1.272 9.479; p = 0.15), ast above 40 iu/l (or: 0.269, 95%ci: 0.179 0.402; p = 0.001), creatinine above 1.4 mg/dl (or: 0.529; 95%ci: 0.344 0.813; p = 0.004), urea above 100 mg/dl (or: 0.327, 95%ci: 0.189 0.567; p = 0.001), and sao2 below 80% (or: 8.754, 95%ci: 5.413 14.156; p = 0.001) were among the independent predictors of covid-19 in-hospital mortality (table 4). to evaluate the diagnostic value of independent risk factors of mortality, the roc curve analysis was used (figure 2 and table 5). sao2 has an excellent diagnostic value for predicting in-hospital mortality of covid-19 patients in cut-off point of 85.5% (67.7% sensitivity, and 56.3% specificity). 4. discussion in this study, which was performed to design a prediction model for hospital mortality in admitted covid-19 patients, 1000 patients who referred to imam reza and sina hospitals in tabriz were studied. the mean age of the patients was 56.34 years, and 65.7% of the patients were male. the mortality rate was 29.9%. evaluation of demographic characterthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e49 table 2: comparing the laboratory findings on admission between survived and non-survived cases variable alive (n=701) dead (n=299) dead (n=1000) p wbc (cells*103 /ml) 7.53±5.29 8.27±7.71 7.75±6.12 0.009 neutrophil (%) 78.93±12.19 81.68±9.90 79.75±11.62 0.001 lymphocyte (%) 20.88±12.27 18.00±10.04 20.02±11.72 0.001 hb (g/dl) 13.46±1.94 12.27±2.15 13.11±2.08 0.061 plt (cells*103 /ml) 235.53±100.71 235.99±119.43 241.05±106.92 0.110 ast (iu/l) 46.11±47.48 60.82±66.04 50.51±54.09 0.001 alt (iu/l) 41.73±38.55 56.46±75.00 46.13±52.58 0.001 alkp (iu/l) 205.01±148.65 203.61±136.81 204.59±145.14 0.443 cr (mg/dl) 1.23±1.12 1.56±1.34 1.33±1.20 0.001 urea (mg/dl) 42.98±32.62 62.85±54.98 48.92±41.60 0.001 pt (sec) 14.13±3.97 14.49±4.29 14.24±4.07 0.111 ptt (sec) 37.73±11.04 41.85±14.50 38.97±12.31 0.101 inr 1.14±0.35 1.17±0.38 1.15±0.36 0.126 na (meq/l) 140.14±3.94 141.07±4.46 140.42±4.12 0.301 k (meq/l) 4.24±0.47 4.30±0.46 4.26±0.46 0.231 ph 7.40±0.03 7.39±0.03 7.40±0.03 0.150 hco3 (meq/l) 25.13±6.66 24.71±6.60 25.01±6.64 0.179 paco2 (mmhg) 41.48±12.61 43.12±13.74 41.97±12.97 0.835 crp 0 273 (38.9) 133 (44.5) 406 (40.6) +1 254 (36.2) 64 (21.4) 318 (31.8) +2 136 (19.4) 88 (29.4) 224 (22.4) 0.746 +3 16 (2.3) 7 (2.3) 23 (2.3) +4 22 (3.1) 7 (2.3) 29 (2.9) * data were analyzed using independent-sample t test and chi-square and presented as mean ± sd and frequency (%). ** wbc: white blood cell; hb: hemoglobin; plt: platelet; ast: aspartate aminotransferase; alt: alanine transaminase; alkp: alkaline phosphatase; cr: creatinine; pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio; na: sodium; k: potassium; crp: c-reactive protein. istics of the studied patients showed that the mean age of the deceased patients was significantly higher (59.36±18.40 vs. 55.05±17.68; p=0.001), and mostly male patients died (71.6% vs. 28.4%; p = 0.011). assessment of clinical signs also showed that the level of sao2 was significantly lower in dead patients. the results showed that hospitalization over five days, ast above 40 iu/l, creatinine above 1.4 mg/dl, urea above 100 mg/dl, and sao2 below 80% were the independent risk factors of in-hospital mortality among covid19 patients. numerous predictive models have been published in recent studies to estimate the risk of nosocomial mortality in patients with covid-19 in eastern and western countries; especially the 4c mortality score, which includes age, sex, number of comorbidities, respiration rate, oxygen saturation, level of consciousness, urea, and c-reactive protein (crp), which were evaluated in a cohort of 35,000 patients and had an excellent prediction power (auc = 0.79) (19). in the present study, patients with covid-19 who died had a higher mean age than other patients. consistent with the present study, studies conducted in china and the united states also introduced a high age as a risk factor for in-hospital mortality but compared to the above studies, the mortality rate in our patients was lower, which seems to be due to differences in demographic variables (4, 20, 21). recent studies have examined various variables in predicting mortality in patients with covid-19 with mild to severe disease and icu admission. for example, the data of 4711 patients with covid-19 were investigated in a study by altschul et al., and the results showed a classification scale for mortality of covid-19 patients with six variables (age, spo2, mean arterial pressure (map), urea, crp, and inr) at the time of admission (22). in the study by liang et al., ten variables (including radiographic chest abnormalities, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, history of cancer, neutrophil to lymphocyte ratio, lactate dehydrogenase (ldh), and direct bilirubin) were evaluated. the results showed that these variables are good predictors of mortality risk in covid-19 patients (23). the study by knight et al. also reported a mortality prediction scale consisting of 8 variables (age, sex, number of comorbidities, respiration rate, spo2, level of consciousness, urea, and crp), the evaluation of which is a good criterion in the initial clinical examination of patients at hospitalization to predict mortality (19). consistent with the above studies, the methods used in studies that used machine learning to predict mortality showed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mohammadi et al. 6 table 3: univariate logistic regression analysis of covid-19 mortality risk factors variable alive (n=701) dead (n=299) or (95% ci) p age (year) < 60 390 (55.6) 150 (50.2) 0.096 60 80 260 (37.1) 111 (37.1) 1.754 (0.932 3.304) 0.082 > 80 51 (7.3) 38 (12.7) 2.340 (0.892 6.138) 0.084 rr (/minute) > 20 5 (1.6) 2 (1.7) 0.747 (0.106 5.282) 0.770 hospitalizations (day) < 5 647 (93) 233 (80.1) 0.001 5 10 40 (5.7) 49 (16.8) 4.401 (1.955 9.906) 0.001 > 10 9 (1.3) 9 (3.1) 4.006 (0.843 19.043) 0.081 wbc (cells*103 /ml) < 4 56 (8.0) 56 (18.7) 0.717 (0.212 1.989) 0.016 4 10 531 (75.7) 170 (56.9) 0.295 (0.128 0.687) 0.004 > 10 114 (16.3) 73 (24.4) 0.354 (0.121 1.034) 0.058 neutrophil (%) < 18 0 0 18 63 69 (9.8) 12 (4.0) > 63 632 (90.2) 287 (96.0) 0.625 (0.205 1.908) 0.409 ast (iu/l) > 40 209 (29.8) 151 (50.5) 6.190 (3.170 12.085) 0.001 alt (iu/l) > 40 305 (43.5) 121 (40.5) 0.287 (0.141 0.582) 0.001 creatinine (mg/dl) > 1.4 96 (13.7) 77 (25.8) 2.673 (1.313 5.444) 0.007 urea (mg/dl) > 100 38 (5.4) 54 (18.1) 2.764 (1.146 6.668) 0.024 o2 saturation (%) < 60 0 (0.0) 0 (0.0) 60 80 37 (5.3) 102 (34.1) 1.289 (0.891 4.313) 0.003 > 80 664 (84.7) 197 (65.9) 0.095 (0.039 0.228) 0.001 * data are presented as frequency (%). ci: confidence interval; or: odds ratio; rr: respiratory rate; wbc: white blood cells; ast: aspartate aminotransferase; alt: alanine aminotransferase. table 4: multivariate logistic regression analysis of covid-19 mortality risk factors variable or (95% ci) p-value hospitalization > 5 days 3.473 (1.272 9.479) 0.015 ast > 40 iu/l 0.269 (0.179 0.402) 0.001 creatinine > 1.4 mg/dl 0.529 (0.344 0.813) 0.004 urea > 100 mg/dl 0.327 (0.189 0.567) 0.001 spo2 < 80% 8.754 (5.413 14.156) 0.001 or: odds ratio; ci: confidence interval; ast: aspartate aminotransferase. table 5: diagnostic value of independent risk factors of covid-19 mortality variable auc (95% ci) p-value cut off point sensitivity specificity hospitalization 0.484 (0.443-0.526) 0.439 ast 0.374 (0.328-0.403) 0.001 36.5 61.9 57.6 creatinine 0.366 (0.335-0.414) 0.001 1.05 48.8 69.4 urea 0.402 (0.362-0.442) 0.001 71 29.6 89.4 spo2 0.705 (0.666-0.745) 0.001 85.5 67.7 56.3 auc: area under the receiver operating characteristic curve; ci: confidence interval; ast: aspartate aminotransferase. that the above variables in covid-19 patients admitted to the icu are good predictors of mortality (24). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e49 in recent studies, the nutritional status of patients with covid-19 with severe disease was evaluated using mnutric criteria at the time of hospitalization, and the results showed that the risk of mortality in patients with high nutritional risk, based on the above criteria, is twice as high as patients with low nutritional risk (25). however, in the present study, the nutritional status of the patients was not studied, and it is better to be considered in future studies. by comparing the present study’s findings with previous studies, we can say that the clinical and paraclinical characteristics of patients and risk factors are different, which seems to be due to differences in the number of samples, demographic characteristics, and status of patients on admission. in addition, logistic regression and roc curve analyses were used to identify the factors affecting inpatient mortality. however, risk regression models or standard cox proportional hazard models were used in some of the other studies (26, 27). another reason for the difference between the present study and other studies is the age of the patients. in the present study, young and middle-aged patients were studied, while in other studies, elderly patients with a mean age over 60 years were studied (22, 24, 25, 28-30). in a multicenter study conducted by gupta et al. on 2215 patients in the united states, nine risk factors (including age, sex, bmi, coronary artery disease (cad), active cancers, hypoxemia, hepatic impairment, renal impairment, and the number of hospital icu beds) were introduced as predictors of 28-day patient mortality (29). in the present study, spo2, urea, creatinine, ast, and hospitalization were the factors that predicted the mortality of patients. in contrast, studies have used non-covid-19 predictive criteria, including the waterlow score, to predict short-term mortality and length of hospital stay in elderly patients. waterlow score is a multidimensional criterion for evaluating bed sores, calculated based on age, nutritional status, weight, patient movement, sex, smoking, comorbidities, and medications used (30). 5. limitations and strengths one of the strengths of this study is the large sample size and evaluation of demographic variables, vital signs, and laboratory findings of patients with covid-19. in addition, the assessment of mortality risk in patients based on patients’ clinical and laboratory findings also increases the applicability of the results of the present study to other patients. limitations of the present study include: some of the patients’ tests were not completely performed and they were excluded from the study. some patients were discharged against medical advice or referred to other centers, and their information could not be fully verified and they were excluded from the study. also, we didn’t evaluate and report the severity of disease. 6. conclusion the mortality rate of patients with covid-19 in our study was 29.9%. hospitalization of more than five days, ast above 40 iu/l, creatinine above 1.4 mg/dl, urea above 100 mg/dl, and sao2 < 80% were the independent risk factors of inhospital mortality of patients with covid-19. 7. declarations 7.1. acknowledgments the researchers acknowledge all study participants and staff of the toxicology ward in the hospitals for their support from the beginning to the end of the research process. 7.2. data availability it can be available after legal permits. 7.3. authors’ contributions all authors participated in the conception and design, acquisition of data, analysis and interpretation of data, drafting of the article, review of the article, and finding approval. 7.4. funding and supports none. 7.5. conflict of interest no potential and actual conflicts of interest were present during our investigation. references 1. phelan al, katz r, gostin lo. the novel coronavirus originating in wuhan, china: challenges for global health governance. jama. 2020;323(8):709-10. 2. gorbalenya ae, baker sc, baric rs, de groot rj, drosten c, gulyaeva aa, et al. the species severe acute respiratory syndrome-related coronavirus: classifying 2019ncov and naming it sars-cov-2. nature microbiology. 2020;5(4):536-44. 3. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 4. wang d, hu b, hu c, zhu f, liu x, zhang j, et al. clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in wuhan, china. jama. 2020;323(11):1061-9. 5. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem z. mohammadi et al. 8 6. schlagenhauf p, ashra h. severe acute respiratory syndrome spreads worldwide. the lancet. 2003;361(9362):1017. 7. team whoer. ebola virus disease in west africa—the first 9 months of the epidemic and forward projections. nejm. 2014;371(16):1481-95. 8. viboud c, simonsen l. global mortality of 2009 pandemic influenza a h1n1. lancet infect dis. 2012;12(9):651-3. 9. dawood fs, iuliano ad, reed c, meltzer mi, shay dk, cheng p-y, et al. estimated global mortality associated with the first 12 months of 2009 pandemic influenza a h1n1 virus circulation: a modelling study. lancet infect dis. 2012;12(9):687-95. 10. nicholls jm, poon llm, lee kc, ng wf, lai st, leung cy, et al. lung pathology of fatal severe acute respiratory syndrome. the lancet. 2003;361(9371):1773-8. 11. chan jf-w, yuan s, kok k-h, to kk-w, chu h, yang j, et al. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet. 2020;395(10223):514-23. 12. wu jt, leung k, leung gm. nowcasting and forecasting the potential domestic and international spread of the 2019-ncov outbreak originating in wuhan, china: a modelling study. the lancet. 2020;395(10225):689-97. 13. mahase e. coronavirus: covid-19 has killed more people than sars and mers combined, despite lower case fatality rate. bmj.2020. 368:m641. 14. fanidi a, jouven x, gaye b. strategies to control covid19 and future pandemics in africa and around the globe. ehj. 2020;41(41):3973-5. 15. covid-19 explorer: who; [available from: https://worldhealthorg.shinyapps.io/covid/. 16. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet. 2020;395(10229):1054-62. 17. li x, xu s, yu m, wang k, tao y, zhou y, et al. risk factors for severity and mortality in adult covid-19 inpatients in wuhan. clin immunol. 2020;146(1):110-8. 18. shakiba m, nazari ssh, mehrabian f, rezvani sm, ghasempour z, heidarzadeh a. seroprevalence of covid-19 virus infection in guilan province, iran. emerg infect dis. 2021;27(2):636-8. 19. richardson s, hirsch js, narasimhan m, crawford jm, mcginn t, davidson kw, et al. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area. jama. 2020;323(20):2052-9. 20. altschul dj, unda sr, benton j, de la garza ramos r, cezayirli p, mehler m, et al. a novel severity score to predict inpatient mortality in covid-19 patients. sci rep. 2020;10(1):1-8. 21. liang w, liang h, ou l, chen b, chen a, li c, et al. development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with covid-19. jama intern med. 2020;180(8):1081-9. 22. pan p, li y, xiao y, han b, su l, su m, et al. prognostic assessment of covid-19 in the intensive care unit by machine learning methods: model development and validation. j med internet res. 2020;22(11):e23128. 23. zhang p, he z, yu g, peng d, feng y, ling j, et al. the modified nutric score can be used for nutritional risk assessment as well as prognosis prediction in critically ill covid-19 patients. clin nutr. 2021;40(2):534-41. 24. mccaw zr, tian l, vassy jl, ritchie cs, lee c-c, kim dh, et al. how to quantify and interpret treatment effects in comparative clinical studies of covid-19. ann intern med. 2020;173(8):632-7. 25. oulhaj a, ahmed la, prattes j, suliman a, alsuwaidi ar, al-rifai rh, et al. the competing risk between in-hospital mortality and recovery: a pitfall in covid-19 survival analysis research. medrxiv.2020;2020.07.11.20151472. 26. zhao z, chen a, hou w, graham jm, li h, richman ps, et al. prediction model and risk scores of icu admission and mortality in covid-19. plos one. 2020;15(7):e0236618. 27. fumagalli c, rozzini r, vannini m, coccia f, cesaroni g, mazzeo f, et al. clinical risk score to predict in-hospital mortality in covid-19 patients: a retrospective cohort study. bmj open. 2020;10(9):e040729. 28. galloway jb, norton s, barker rd, brookes a, carey i, clarke bd, et al. a clinical risk score to identify patients with covid-19 at high risk of critical care admission or death: an observational cohort study. j infect. 2020;81(2):282-8. 29. gupta s, hayek ss, wang w, chan l, mathews ks, melamed ml, et al. factors associated with death in critically ill patients with coronavirus disease 2019 in the us. jama intern med. 2020;180(11):1436-47. 30. wang jw, smith p, sarker s-j, elands s, oliveira a, barratt c, et al. can waterlow score predict 30-day mortality and length of stay in acutely admitted medical patients (aged≥ 65 years)? evidence from a single centre prospective cohort study. bmj open. 2019;9(11):e032347. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations and strengths conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 162 emergency (2014); 2 (4): 162-165 original research a survey of patients' satisfaction in emergency department of rasht poursina hospital behzad zohrevandi, hosna tajik* road trauma research center, guilan university of medical sciences, rasht, iran abstract introduction: patients' satisfaction (ps) is one of the important indicators of emergency care quality and outcomes of health care services. some researchers believe that improve the work processes and hospital quality are not possible without caring to comments, requirements, expectations, and satisfaction of patients. the percent study was aimed to assess the emergency department (ed) ps of poursina hospital, rasht, iran. methods: in this descriptive cross sectional study, the samples was selected from 378 patients admitted to ed of poursina hospital, rasht, iran, 2013. for each patient a check list and a questionnaire, including 37 questions about ps, were filled that had categories like physical comfort and residential aspects, physicians care, nurse care, behavioral aspect, and waiting time for service presentation. data were analyzed by spss version 16. results: entirely, 378 patients were entered to the study with mean age of 38.44±17.8 (60.8% male). the mean score of total satisfaction of ed patients was 106.94±13.62 (range: 72-144). the mean score of physical comfort was 33.25±4.76 out of the highest obtainable score of 55, nurse care 25.33±5.13 out of 40, physician care 24.34±3.38 out of 40, waiting time for services 13.42±5.48 out of 30, and behavioral aspects 10.58±2.66 out of 20. there were significant relation among ps, sex (p=0.0001), and the shift of admission (p=0.023). conclusion: the findings of percent study showed that giving services to emergency clients in various fields such as physical comfort and residential aspects, physicians care, nurse care, and the total ed satisfaction is relatively agreeable. the periodic and continuous assessment as well as comparison of satisfaction and dissatisfaction parameters during the time, before and after performing the changes, could be effectual. key words: patient satisfaction; emergency service, hospital; health care quality, access, and evaluation; patient safety cite this article as: zohrevandi b, tajik h. a survey of patients' satisfaction in emergency department of rasht poursina hospital. emergency. 2014;2(4):162-65. introduction:1 atients' satisfaction (ps) is one of the important indicators of emergency care quality and outcomes of health care services (1-3). some researchers believe that improve the work processes and hospital quality are not possible without caring to comments, requirements, expectations, and satisfaction of patients. thus, ps has increasingly turned to one of the significant tools in evaluation of hospital performances (2). ps is not a new concept, but because of predominance of customer-focused strategy in health care services, using satisfaction index of health care clients has been entered to the evaluation scope of hospitals since two decades ago (4, 5). ps is the measure of quality in health care understood by patients and the resultant of different complicated factors (6). several *corresponding author: hosna tajik; road trauma research center, guilan university of medical sciences, poursina hospital, rasht, iran. phone: +989112758369. fax: +981313238373 email: hosnatajik@yahoo.com received: 1 jun 2014; accepted: 29 june 2014 factors should be coordinated with each other to make an appropriate condition for creation and development of ps with observing patient's right completely in all aspects (7). getting ps is one of the principles of medical ethics and the physician should have consult with patient in making any decision. daily, several patients with serious condition are referred to the emergency department (ed) of hospitals. considering to the especial importance of ed, increase the satisfaction in this ward has a remarkable effect on people's attitude toward the hospital (ed is the symbol of the whole hospital). eds are confronted with challenging issues lead to reduce the ps (1). the satisfaction of ed clients cannot be achieved without assessment, study, and practical plan to promote the quality of services (2). noticing to this issue, this study was performed to find effective factors on patient satisfaction and enhance them toward improve the quality of ed services. methods: p mailto:hosnatajik@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 163 zohrevandi et al study design and setting in this cross-sectional study, cases were chosen by a regular random selection among referees to the ed of poursina hospital, rasht, iran, in 2012. totally, 378 patients were enrolled and selected in this study. inclusion criteria were having age over 15 years and hospitalization in the emergency center for more than five hours. exclusion criteria were significant impairment of cognition (attention, recent memory, understanding questions, etc.), having a very bad ill appearance so that the patient could not answer the questions, and patients died. selected patients after ending their hospitalization at the ed were interviewed by project partners trained to have dealing with patients and design the questionnaire in a way to prevent patient's bias in answering. patients were asked in a calm condition (without presenting of health care and non-health care stuffs). no comment was put on the files of patients entered to the study. the patients who had enough literacy to fill the questionnaire filled it by themselves if not; it was read by the questioner for them to answer. during reading the questions, there was no shift or bias in expressing by the questioner. questionnaire for evaluating of ps, the omidvari et al. questionnaire contained 39 questions was used (8). two questions (about elevators' status and using bathroom in ed) in the welfare facility section were removed because they were not applicable in the studied department. final questionnaire had 37 questions in five sections including physicians care (8 questions), nurse care (8 questions), behavioral aspects (4 questions), physical comfort and residential aspects (11 questions), and waiting time to receive emergency services (6 questions). cronbach's coefficient alpha for whole questionnaire (37 questions) was 0.91 and for each section as follow: 0.89 in physicians care, 0.90 nurse care, 0.70 behavioral aspects, 0.93 physical comfort and residential aspects, and 0.70 waiting time. there was five options for answering to each question based on likert scale, which scores of five to one given to answers very much, very, average, low, and very low, respectively. in evaluating of each question, low and very low answers were considered as dissatisfaction. in some questions, regarding the feedback of responders, the sixth option was added which means that the question was not applicable. therefore, the scores of 11-55 were determined for physical comfort and residential aspects, 8-40 for physicians and nurse care, 4-20 for behavioral aspects, 6-30 for the waiting time to receive emergency services, and 37-185 for total satisfaction. the poor, average, and good scores were defined for each section as below: for physical comfort and residential aspects respectively 11-25, 26-40, and 41-55, physicians and nurse care 818, 19-29, and 30-40, behavior aspects 4-9, 10-14, and 15-20, the waiting time to receive emergency services 6-13, 14-22, and 23-30, and total satisfaction 37-85, 86135, and 136-185. background information such as age, sex, marital status, education level, history of hospitalization in the studied ed, the work shift patients referred, the length of staying in ed, the general comment of patient regarding ed, and total satisfaction level of the patient were separately collected in specific designed data sheets. statistical analysis description of qualitative variables was performed by frequency tables and quantitative variables by calculation of mean ± standard deviation. after computation of scores, each of five section and total of satisfaction scores (comprehensive satisfaction) were assessed, then the distribution of achieved scores was analyzed using kolmogorovsmirnov test (ks test). statistical analysis was done using spss version 16. the significant level was considered as p<0.05. results: entirely, 378 patients were entered to the study with mean age of 38.44±17.8 (60.8% male). table 1 summarized the background information of studied patients. 336 (88.8%) patients did not have the history of hospitable 1: the background information of studied patients  background information number (%) sex male 230 (60.8) female 148 (39.2) age 15-35 210 (55.6) 36-50 86 (22.8) 51-65 40 (10.6) 65< 42 (11.1) education below diploma 156 (41.3) diploma to graduate 210 (55.6) graduated 12 (3.2) marital status single 97 (25.7) married 281 (74.3) the history of hospitalization yes 32 (8.5) no 346 (91.5) the shift of ed admission morning shift 163 (43.1) evening shift 79 (20.9) night shift 136 (36) duration of hospitalization (hours) <6 90 (23.8) 6-12 166 (43.9) 12-18 68 (18) 18< 54 (14.3) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (4): 162-165 164 talization in ed. one hundred sixty three (43.1%) cases were hospitalized in the morning shift, 136 (36%) ones in night, and the rest in evening. regarding ed length of stay, 90 (23.8%) patients were hospitalized less than six hours (table1). table 2 shows the mean satisfaction scores of five sections as well as total satisfaction score. the mean score of total satisfaction of ed patients was 106.94±13.62 (range: 72-144). the mean score of physical comfort was 33.25±4.76 out of the highest obtainable score of 55, nurse care 25.33±5.13 out of 40, physician care 24.34±3.38 out of 40, waiting time for services 13.42±5.48 out of 30, and behavioral aspects 10.58 ±2.66 out of 20. distribution of mean satisfaction scores in each five sections was categorized based on predefined scores (the poor, average, good) in table 3 and figure 1. the analysis showed a significant correlation between total ed satisfaction with sex (p=0.0001) and admission shift (p=0.023). such a relation was not seen between total ed satisfaction and age (p=0.33), marital status (p=0.12), educational level (p=0.68), the previous history of ed (p=0.26), ed length of stay (p=0.07). the total ed satisfaction score was 2.9 out of 5 compare to whole hospital satisfaction 2.78 out of 5 (p<0.05). discussion: the findings showed the total satisfaction score of studied ed as an average level, based on pre-defined level. among five studied sections, waiting for service time and behavioral aspects gained the maximum dissatisfaction with 53.2% and 44.2% poor level, respectively. here, total score of each five assessed sections related to physical comfort and residential aspects, physicians care, nurse care, behavioral aspects, and waiting time for service are on average level; but the noticeable point was about nurse care aspect that with 18.3% of good score had the best level among five sections. in addition, behavioral aspect and waiting time for services had the average scores among five sections with 44.2% and 53.2%, respectively. a significant relationship was seen between total satisfaction and admission shift so that the morning shift, as the most crowded work shift, had the highest level of ps. the study of pines et al. about the effect of ed crowding on ps revealed an indirect effect of crowding on satisfaction (9). also weiss et al. showed significant relationship between the ed overcrowding and the number of patients who leave ed without being seen as one of the probable indicators of ps (10). interesting findings of the present study could be arisen from the high number of ed stuffs in the morning shift, subsequently the better speed and quality of services than other times. it seems that the number of stuffs, quality and duration of services, and considering the needs of patients should be more noted to prevent such problems. in this project, there was near significant correlation (p=0.07) between the length of ed stay and ps. the study of rodi and colleagues declared that all domains of ps were significantly correlated with the length of stay (11). christopher et al. concluded that reducing the length of ed stay is direct table 2: mean satisfaction scores in each five sections were categorized based on pre-defined scores  sections mean± sd (range) physical comfort and residential aspects 33.2±4.8 (23-43) physicians care 24.3±3.4 (14-34) nurse care 25.3±5.1 (13-38) behavioral aspects 10.6±2.7 (4-18) waiting time for service 13.4±5.5 (6-30) total satisfaction 106.9±13.6 (72-144) table 3: mean satisfaction scores in each five sections were categorized based on pre-defined scores  sections the poor n (%) the average n (%) the good n (%) physical comfort and residential aspects 12 (3.2%) 341 (90.2%) 25 (6.6%) physicians care 21 (5.6%) 328 (86.8%) 29 (7.7%) nurse care 25 (6.6%) 284 (75.1%) 69 (18.3%) behavioral aspects 167 (44.2%) 173 (45.8%) 38 (10.1%) waiting time for service 201 (53.2%) 155 (41.0%) 22 (5.8%) total satisfaction 18 (4.8%) 351 (92.9%) 9 (2.4%) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 165 zohrevandi et al relation with decrease in the number of patients who leave without seeing a physician (12). regarding behavioral aspect, holding workshops about how deal with patients and justify physicians, students of ed, nurses, and stuffs could greatly help improving ps regarding behavioral aspect. some researchers believe that the viewpoint of patients into waiting time has a more critical role in satisfaction level than the real waiting time (11, 13). in other words, it is probable that waiting time has been justified for patients with explaining about the reason of expectation and necessary woks done in the estimated time. moreover, because of the enormous workload of physicians in ed of poursina hospital, it is not possible to explain the disease, incidence, and treatment processes performed by physician in all details for each patient; thus, by increasing the number of physicians in these centers, the assignments of these persons can be decreased and the satisfaction level of patients improved, too. efforts should be focused in decrease the waiting time for services and improve the behavioral aspects of stuffs. to reach this goal, using the results of periodic assessment of ps level, as a critical indicator in health care quality and applying it in quality management is necessary to create changes based on achieved results. because perform changes in services presentation needs the intervention in terms of the project. conclusion: the findings of percent study showed that giving services to emergency clients in various fields such as physical comfort and residential aspects, physicians care, nurse care, and the total ed satisfaction is relatively agreeable. the periodic and continuous assessment as well as comparison of satisfaction and dissatisfaction parameters during the time, before and after performing the changes, could be effectual. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of poursina hospital of rasht, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. taylor c, benger j. patient satisfaction in emergency medicine. emerg med j. 2004;21(5):528-32. 2. aiken lh, sermeus w, van den heede k, et al. patient safety, satisfaction, and quality of hospital care: cross sectional surveys of nurses and patients in 12 countries in europe and the united states. bmj. 2012;344. 3. cleary pd, mcneil bj. patient satisfaction as an indicator of quality care. inquiry. 1988;25(1):25-36. 4. larsen dl, attkisson cc, hargreaves wa, nguyen td. assessment of client/patient satisfaction: development of a general scale. eval program plann. 1979;2(3):197-207. 5. pascoe gc. patient satisfaction in primary health care: a literature review and analysis. eval program plann. 1983;6(3):185-210. 6. andaleeb ss. service quality perceptions and patient satisfaction: a study of hospitals in a developing country. soc sci med. 2001;52(9):1359-70. 7. rahmqvist m, bara a-c. patient characteristics and quality dimensions related to patient satisfaction. int j qual health care. 2010;22(2):86-92. 8. omidvari s, shahidzadeh a, montazeri a, azin sa, harirchi am, h. s. patient satisfaction survey in the hospitals of tehran university of medical sciences, tehran, iran. payesh. 2008;7(2):141-52. [persian]. 9. pines jm, iyer s, disbot m, hollander je, shofer fs, datner em. the effect of emergency department crowding on patient satisfaction for admitted patients. acad emerg med. 2008;15(9):825-31. 10. weiss sj, ernst aa, derlet r, king r, bair a, nick tg. relationship between the national ed overcrowding scale and the number of patients who leave without being seen in an academic ed. am j emerg med. 2005;23(3):288-94. 11. rodi sw, grau mv, orsini cm. evaluation of a fast track unit: alignment of resources and demand results in improved satisfaction and decreased length of stay for emergency department patients. qual manag health care. 2006;15(3):163-70. 12. fernandes c, price a, christenson jm. does reduced length of stay decrease the number of emergency department patients who leave without seeing a physician? j emerg med. 1997;15(3):397-9. 13. obamiro jk. effects of waiting time on patient satisfaction: nigerian hospitals experience. j econ behav. 2013;3(1):117-26. figure 1: distribution of emergency department (ed) satisfaction level in comparison to whole hospital condition  emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 125 emergency (2014); 2 (3): 125-129 original research outcome of patients underwent emergency department thoracotomy and its predictive factors shahram paydar, abdoshahid moghaninasab, elham asiaei, golnar sabetian fard jahromi, shahram bolandparvaz, hamidreza abbasi* trauma research center, shiraz university of medical sciences, shiraz, iran abstract introduction: emergency department thoracotomy (edt) may serve as the last survival chance for patients who arrive at hospital in extremis. it is considered as an effective tool for improvement of traumatic patients’ outcome. the present study was done with the goal of assessing the outcome of patients who underwent edt and its predictive factors. methods: in the present study, medical charts of 50 retrospective and 8 prospective cases underwent emergency department thoracotomy (edt) were reviewed during november 2011 to june 2013. comparisons between survived and died patients were performed by mann-whitney u test and the predictive factors of edt outcome were measured using multivariate logistic regression analysis. p < 0.05 considered statistically significant. results: fifty-eight cases of edt were enrolled (86.2% male). the mean age of patients was 43.27±19.85 years with the range of 18-85. the mean time duration of cpr was recorded as 37.12±12.49 minutes. eleven cases (19%) were alive to be transported to or (defined as ed survived). the mean time of survival in ed survived patients was 223.5±450.8 hours. more than 24 hours survival rate (late survived) was 6.9% (4 cases). only one case (1.7%) survived to discharge from hospital (mortality rate=98.3%). there were only a significant relation between ed survival and sbp, gcs, cpr duration, and chest trauma (p=0.04). the results demonstrated that initial sbp lower than 80 mmhg (or=1.03, 95% ci: 1.001-1.05, p=0.04) and presence of chest trauma (or=2.6, 95% ci: 1.75-3.16, p=0.02) were independent predictive factors of edt mortality. conclusion: the findings of the present study showed that the survival rate of trauma patients underwent edt was 1.7%. in addition, it was defined that falling systolic blood pressure below 80 mmhg and blunt trauma of chest are independent factors that along with poor outcome. key words: thoracotomy; emergency department; cardiopulmonary resuscitation; heart arrest; outcome assessment cite this article as: paydar sh, moghaninasab a, asiaei e, sabetian fard jahromi g, bolandparvaz sh, abbasi h. outcome of patients underwent emergency department thoracotomy and its predictive factors. emergency. 2014;2(3):125-9. introduction:1 mergency department thoracotomy (edt) may serve as the last survival chance for patients who arrive at hospital in extremis. this method was first described in 1896 (1). the purpose of edt is immediate access to the chest cavity to (a) release of pericardial tamponed, (b) control of cardiac and intrathoracic haemorrhage, (c) evacuate massive air embolism, (d) open cardiac massage, and (e) place a descending thoracic aortic cross-clamp (2). edt is considered as an effective tool for improvement of traumatic patients’ outcome (3). two indications were defined for edt. the first is salvageable post traumatic cardiac arrest (patients sustaining witnessed penetrating trauma *corresponding author: shahram bolandparvaz; trauma research center, shahid rajaei trauma hospital, shahid chamran blvd, shiraz, iran. tel/fax: +987116254206. email: abasihr@sums.ac.ir received: june 2014; accepted: july 2014 with <15 minutes of pre-hospital cardio pulmonary resuscitation (cpr), or witnessed blunt trauma with <5 minutes of pre-hospital cpr) and the second relates to persistent severe post traumatic hypotension (systolic blood pressure ≤60 mmhg) due to cardiac tamponed, intra-thoracic and intra-abdominal hemorrhage, as well as cervical air embolism. there are several accessible studies during two to three decades ago which have evaluated the efficiency of edt and predictive factors of their outcomes (3-5). the findings of these projects were variable so that some researchers believe that performing of edt causes to increase the longevity of the person while others do not have such an idea. the trauma mechanism (blunt or penetrating), injury location, transferring time duration, etc. are predictive factors mentioned as effective agents in edt outcomes. studies consider a survival rate between 1.4-18 % for patients after edt (3, 6, 7). a recent review stated the e mailto:abasihr@sums.ac.ir this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com paydar et al 126 necessity of developing specific guidelines for edt in patients benefit from this procedure. in this review, patients most likely to benefit from edt were those with penetrating chest trauma, signs of life at scene or on arrival in the ed or pericardial tamponed (4). of course, the high cost of edt performing which is paid by the patient and health care system should not be disregarded. the treatment cost for each patient is between 13000-14000 dollars, while the cost of cpr is about 892-7200 dollars (8, 9). in addition, presentation of some blood-borne diseases in staffs, ethical issues, and bad neurological outcomes are the main obstacles of edt (10-13). thus, the present study was done with the goal of assessing the outcome of patients who underwent edt and its predictive factors. methods: study design and setting in the present study, medical charts of 50 retrospective and 8 prospective cases underwent emergency department thoracotomy (edt) were reviewed to evaluate the outcome of edt at shahid rajaee trauma center, shiraz, iran during november 2011 to june 2013. the study protocol was not interfere to the standard treatment and approved with local ethic committee. participants all cases performed emergency thoracotomies at ed were included while all operation room (or) thoracotomies excluded (except for or thoracotomies that were done following edt). it was considered that a minimum sample size with 44 patients could be appropriate to evaluate edt outcomes, based on 1.5% of the survival rate (14), α=0.05, power of 90% (β=0.1), and 0.3 error. data collection thoracotomies were performed by a general surgery senior resident or a general surgeon. edt included a left anterolateral thoracotomy, pericardiotomy, open cardiac massage, and descending thoracic aorta clamping. those who survived, had emergency or thoracotomies. information about patient’s age and sex, type of injury (blunt, penetrating), arrival vital signs such as systolic blood pressure (sbp), heart rate (hr), respiratory rate (rr), glasgow coma scale (gcs), venous blood gas parameters (vbg), transfused packed red blood cells, insertion of central venous line (cvl), focused abdominal ultrasonography for trauma (fast), chest xray (cxr), pelvic x-ray, deep peritoneal aspiration (dpa), edt indications, and results were gathered. outcome the early survivors was defined as those who survived to be transferred to operation room (or) and late survivors as those who survived ≥ 24hours at intensive care unit (icu). statistical analysis data were analyzed by stata version 11.0. survival rate was defined as frequency and percentage. comparisons between survived and died patients were performed by mann-whitney u test. finally, for determining the predictive factors of edt outcome multivariate logistic regression analysis was used. p < 0.05 considered statistically significant. results: in this study, 58 cases underwent edt following multiple trauma (94.8% blunt trauma) were examined. table 1 shows the demographic and baseline characteristics of studied patients. the mean age of patients was 43.27±19.85 years with the range of 18-85 (86.2% male). the mean of sbp, hr, and rr on arrival to the ed were 62.10±45.12 mmhg, 83.31±50.24/minute (no detectable to 170), and 13.60±12.63/minute (no detectable to 47), respectively. in addition, the mean gcs of patients on arrival was 6.81±4.62. the mean interval time between ed arrival and edt performance was 42.12±67.50 minutes (0-429). the mean time duration of cpr was recorded as 37.12±12.49 minutes. eleven cases (19%) were alive to be transported to or table 1: demographic and baseline characteristics of studied patients  variable total n (%) ed survived n (%) age 18-29 21 (36.2) 3 (27.3) 30-44 13 (22.4) 2 (18.2) 45-59 9 (15.5) 1 (9.1) >60 15 (25.9) 5 (45.4) gender male 50 (86.2) 10 (90.9) female 8 (13.8) 1 (9.1) type of trauma car to car accident 11 (19.0) 2 (18.2) car to pedestrian 21 (36.2) 3 (27.3) car turn over 6 (10.3) 2 (18.2) motor to car accident 9 (15.5) 1 (9.1) motor turn over 2 (3.45) 1 (9.1) fall 4 (6.9) 1 (9.1) gun shot 3 (5.2) 1 (9.1) other 2 (3.45) 0 (0) associated injuries pericardial tamponade 3 (5.2) 1 (9.1) rib fracture 10 (17.2) 1 (9.1) hemothorax 50 (86.2) 1 (9.1) great vessels injury 3 (5.2) 1 (9.1) lung injury 4 (6.9) 0 (0) cardiac injury 2 (3.4) 1 (9.1) head trauma 34 (58.6) 5 (15.4) abdominal trauma 11 (19) 3 (27.3) extremities trauma 24 (41.4) 5 (15.4) edt indication cardiac arrest 28 (48.2) 7 (63.6) shock 30 (51.8) 4 (36.4) shock index >0.8 50 (86.2) 10 (90.9) <=0.8 8 (13.8) 1 (9.1) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 127 emergency (2014); 2 (3): 125-129 (defined as ed survived). table 1 shows the demographic and baseline characteristics of ed survived patients. the mean time of survival in ed survived patients was 223.5±450.8 hours. table 2 summarizes the diagnostic and therapeutic interventions during edt. more than 24 hours survival rate (late survived) was 6.9% (4 cases). only one case (1.7%) survived to discharge from hospital (mortality rate=98.3%) (figure 1). among different variables including age (p=0.3), sex (p=0.6), type of trauma (p=0.8), associated injuries (p>0.05), sbp (p=0.01), hr (p=0.09), rr (p=0.04), gcs (p=0.02), vbg parameters (p>0.05), fast results (p=0.26), dpa results (0.67), edt indication (0.38), and duration of cpr (p=0.04) there were only a significant relation between ed survival and sbp, gcs, cpr duration, and chest trauma (p=0.04). table 3 shows the results of multivariate logistic regression analysis. the results demonstrated that initial sbp lower than 80 mmhg (or=1.03, 95% ci: 1.001-1.05, p=0.04) and presence of chest trauma (or=2.6, 95% ci: 1.75-3.16, p=0.02) were independent predictive factors of edt mortality. discussion: the findings of the present study showed that the rate of final survival of trauma patients underwent edt was 1.7%. in addition, it was defined that falling systolic blood pressure below 80 mmhg and blunt trauma of chest are independent factors that along with poor outcome. based on trauma guidelines, thoracotomy in patients with penetrating injuries, those who have vital signs, and referring to the ed within the first 15 minutes after injury have appropriate outcomes (5). however, some researchers believe that edt performing in patients with blunt trauma and ischemia can be helpful (15, 16). the present findings are compatible with previous studies. it is probable that blood pressure over 80 mmhg be representative of less duration from the initial injury. because in initial steps of damage compensatory mechanisms are performed and try to keep blood pressure in the normal range. however, in case of patient deterioration, these mechanisms cannot maintain the homeostasis and this gradually leads to disappear the vital signs of the patient. as a result, although in this study the time interval between the occurrence of the event and edt performing didn’t have any effect on the patients’ outcome, because of affecting the level of blood pressure, it can be stated that patients referred sooner to the ed have more survival chance. one of the reasons that this time interval had no effect on patients’ outcome was that recording the times of rate in their study population, while boyd et al. had 7% (10, 17). in a review of 463 cases, lorenz et al. events, ambulance arrival, and edt performing were not accurate and consequently their findings were not reliable. passos et al. studies revealed that lots of ischemia times were not accurately recorded and thus evaluation of time interval between ischemia and edt performing was not accessible (17). on-arrival systolic blood pressure significantly correlated with those who reached or. it seems that systolic blood pressure on presentatable 2: diagnostic and therapeutic interventions during emergency department thoracotomy  interventions total n (%) ed survived n (%) pack cell 48 (82.8) 10 (90.9) chest tube 32 (55.2) 6 (54.6) central venous line 41 (70.7) 11 (100) chest x-ray 18 (31.3) 5 (45.4) pelvic x-ray 3 (5.2) 1 (9.1) fast positive 12 (34.3) 4 (50.0) negative 23 (65.7) 4 (50.0) deep peritoneal lavage positive 15 (39.5) 3 (33.3) negative 23 (60.5) 6 (66.6) * focused abdominal ultrasonography for trauma. table 3: the results of multivariate logistic regression analysis regarding the predictive factors of outcome factors odds ratio 95% confidence interval p value systolic blood pressure 1.03 1.001-1.05 0.04 blunt chest trauma 2.6 1.75-3.16 0.02 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com paydar et al 128 tion could be considered as predictive factor in both early and late survivors. wyrick et al. found that the absence of on-arrival signs of life could be a predictive factor among their early mortality group (18). in addition, profound (blood pressure <60mmhg) and mild shock (blood pressure 60-90 mmhg) were associated with survival rates of 56% and 64%, respectively in cases with penetrating cardiac trauma and resultant cardiac arrest in one study (8). millham et al. declared that edt survivors had a detectable pulse or blood pressure either in pre-hospital or on presentation to ed (7). in comparison with some studies, we had a nearly similar outcomes based on cases who were alive and transported to or. considering to 98.3% mortality rate for cases in this study and the fact that the majority of them sustained blunt trauma, it was suggested that edt for cases of blunt trauma should be meticulously selected. as mentioned before, only one survivor was discharged (1.7%). rhee et al. in a study of cases underwent edt over 25 years, reported an overall survival rate of 7.4% (19). champion et al. displayed 11 % survival. found 13% of overall survival rate (20). the major cause of such discrepancy arises from the types of injuries which was studied; so that in the present project, 55 (94.8%) of patients suffered from blunt trauma. in the text review, also when the findings limited to edts, which were performed in blunt trauma, the survival rate of patients has been noticeably decreased. for example, brown et al. reported no survivor among their 11 blunt trauma cases (16). others found blunt trauma cases survival rates of 0% (10, 12), 0.6% (11), 2% (8),6% (5), and 12.5% (15). tan et al. reported 8 (12%) neurologically intact blunt trauma survivors (4). balkan et al. revealed six patients who underwent edt for blunt cardiac trauma and (one case) 16.7% survival rate (12). capote et al. found 93% mortality rate for blunt trauma cases (8). also, champion et al. reported five patients survived to operation room with three cases who died in or and two ones expired on fifth postoperative day (in addition to their ten cases discharged) (20). thirty-three cases of mollberg et al. study (27.5%) survived to reach or, while seven (5.8%) survived to discharge (12). the current study in comparison with the previously mentioned studies, had eleven cases (19%) were referred to operation room and four (6.9%) survived or to reach icu and one (1.7%) survived to discharge. despite of edt advantages, the costs and risks associated with indiscriminate performance of edt is high. several study have demonstrated that edt is correlated with increased risk of exposure to blood-borne pathogens and permanent neurologic impairment (3, 6). also, some studies have revealed (21, 22). recently, seamon et al. reported that 74% of survived patients had long-term social, cognitive, functional, or psychological impairment after edt (3). noticing to different ideas about the resultants of edt, a definitive comment regarding its performing on different patients is dependent on more studies. one of the important aspects, which should be considered in future studies, is categorizing the patients in terms of clinical factors such as trauma mechanism. conclusion: the findings of the present study showed that the survival rate of trauma patients underwent edt was 1.7%. in addition, it was defined that falling systolic blood pressure below 80 mmhg and blunt trauma of chest are independent factors that along with poor outcome. acknowledgments: the authors kindly appreciate the staffs of the trauma center of shahid rajaei hospital, shiraz, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. flynn tc, ward re, miller pw. emergency department thoracotomy. ann emerg med. 1982;11(8):413-6. 2. sersar si, alanwar ma. emergency thoracotomies: two center study. j emerg trauma shock. 2013;6(1):11-5. 3. seamon mj, chovanes j, fox n, et al. the use of emergency department thoracotomy for traumatic cardiopulmonary arrest. injury. 2012;43(9):1355-61. 4. tan b, pothiawala s, ong m. emergency thoracotomy: a review of its role in severe chest trauma. minerva chir. 2013;68(3):241-50. 5. cothren cc, moore ee. emergency department thoracotomy for the critically injured patient: objectives, indications, and outcomes. world j emerg surg. 2006;1(1):4. figure 1: survival estimation of edt patients.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 129 emergency (2014); 2 (3): 125-129 6. lorenz hp, steinmetz b, lieberman j, schecter wp, macho jr. emergency thoracotomy: survival correlates with physiologic status. j trauma. 1992;32(6):780-8. 7. millham fh, grindlinger ga. survival determinants in patients undergoing emergency room thoracotomy for penetrating chest injury. j trauma. 1993;34(3):332-6. 8. rhee pm, acosta j, bridgeman a, wang d, jordan m, rich n. survival after emergency department thoracotomy: review of published data from the past 25 years. j am coll surg. 2000;190(3):288-98. 9. rabinovici r, bugaev n. resuscitative thoracotomy: an update. scand j surg. 2014;103(2):112-9. 10. burlew cc, moore ee. initial trauma management, resuscitative thoracotomy. encyclopedia intensive care med. 2012:1238-44. 11. khorsandi m, skouras c, shah r. is there any role for resuscitative emergency department thoracotomy in blunt trauma? interact cardiovasc thorac surg. 2013;16(4):509-16. 12. mollberg nm, glenn c, john j, et al. appropriate use of emergency department thoracotomy: implications for the thoracic surgeon. ann thorac surg. 2011;92(2):455-61. 13. powell dw, moore ee, cothren cc, et al. is emergency department resuscitative thoracotomy futile care for the critically injured patient requiring prehospital cardiopulmonary resuscitation? j am coll surg. 2004;199(2):211-5. 14. vassiliu p, yilmaz t, degiannis e. on the ideal emergency thoracotomy incision. world j surg. 2014;38(4):1001-2. 15. thomas mo, ogunleye eo. emergency thoracotomy: indications and management challenges in a developing world. world j cardiovasc surg. 2012;2:1. 16. brown se, gomez ga, jacobson le, scherer 3rd t, mcmillan ra. penetrating chest trauma: should indications for emergency room thoracotomy be limited? am surg. 1996;62(7):530-3. 17. passos em, engels pt, doyle jd, et al. societal costs of inappropriate emergency department thoracotomy. j am coll surg. 2012;214(1):18-25. 18. wyrick dl, dassinger ms, bozeman ap, porter a, maxson rt. hemodynamic variables predict outcome of emergency thoracotomy in the pediatric trauma population. j pediatr surg. 2014;[in press]. 19. mazzorana v, smith rs, morabito dj, brar hs. limited utility of emergency department thoracotomy. the american surgeon. 1994;60(7):516-20. 20. champion j, mckernan j. comparison of minimally invasive thoracoscopy versus open thoracotomy for staging lung cancer. int surg. 1995;81(3):235-6. 21. velmahos gc, degiannis e, souter i, allwood ac, saadia r. outcome of a strict policy on emergency department thoracotomies. arch surg. 1995;130(7):774-7. 22. keller d, kulp h, maher z, santora ta, goldberg aj, seamon mj. life after near death: long-term outcomes of emergency department thoracotomy survivors. journal of trauma and acute care surgery. 2013;74(5):1315-20. archives of academic emergency medicine. 2022; 10(1): e5 or i g i n a l re s e a rc h remote analysis and transmission system of electrocardiogram in prehospital setting; a diagnostic accuracy study elmira almukhambetova1, murat almukhambetov1, abdugani musayev1∗, ainur yeshmanova1, vildan indershiyev1, zhadira kalhodzhaeva1 1. department of emergency and first aid, asfendiyarov kazakh national medical university, almaty, kazakhstan. received: november 2021; accepted: november 2021; published online: 1 january 2022 abstract: introduction: one of the trends in the development of medical technologies is considered to be telemedicine. this study aimed to evaluate the accuracy of a remote electrocardiogram (ecg) analysis and transmission system in prehospital setting. methods: in this cross-sectional study, the data of 19,265 ecgs was gathered from emergency medical service (ems) database of almaty city, kazakhstan, from 2015 to 2019. all ecgs were recorded in the prehospital setting by a paramedic, using "poly-spectrum" ecg recording device. subsequently, all ecgs were sent to the cardiologist for interpretation and the findings were compared between software and cardiologist. results: 19,265 ecgs were registered. the average time from taking ecgs to receiving an expert’s conclusion was 9.2 ± 2.5 minutes. the medical teams were called in 17.9% of cases after paramedic ecg recording; however, in the rest of the cases there was no need to call those teams. using the device reduced the number of visits of specialist teams. the overall sensitivity, specificity, and accuracy of ecg analysis device in diagnosis of ecg abnormalities were 83.8% (95%ci: 82.6 – 84.9), 95.5% (95%ci: 95.1 – 95.8), and 93.3% (95%ci: 92.9 – 93.7), respectively. conclusion: the findings of this study showed the 93.3% accuracy of automatic ecg analysis device in interpretation of ecg abnormalities in prehospital setting compared with the cardiologist interpretations. using the device causes a decrease in the number of cardiologist visits needed as well as reduction in cost and elapsed time. keywords: cardiovascular system; cardiovascular diseases; diagnosis; quality of health care; health services administration cite this article as: almukhambetova e, almukhambetov m, musayev a, yeshmanova a, indershiyev v, kalhodzhaeva z. remote analysis and transmission system of electrocardiogram in prehospital setting; a diagnostic accuracy study. arch acad emerg med. 2022; 10(1): e5. https://doi.org/10.22037/aaem.v10i1.1399. 1. introduction one of the trends in development of medical technologies is considered to be telemedicine, the main goal of which is to create conditions to make the consultation of highly qualified experts easily accessible to ordinary citizens (1, 2). considering the high prevalence and burden of cardiovascular diseases, the importance of a simple and accessible electrocardiography (ecg) analysis tools in prehospital settings is clear (3, 4). thanks to the development of computer technologies, communication networks and the internet have ∗corresponding author: abdugani musayev; department of emergency and first aid, asfendiyarov kazakh national medical university, almaty, kazakhstan. mail index: 050038. nurkent microdistrict, house number 41, flat number 38. tel: +77772509406, e-mail: musaev.dr56@gmail.com, orcid: http://orcid.org/0000-0001-7782-6255. made it possible to register an ecg anywhere and share it over long distances (5, 6). the first experiments of ecg transmission over a significant distance took place at the beginning of the 20th century (7). in 1905, w. einthoven transmitted an ecg at a distance of about 1.5 kilometers (8). the method of remote analysis and transmission of ecg began to spread in the 1960s with the emergence of technical capabilities that made it possible to achieve the sufficient quality of ecg reception (9-12). in some cases, the description and interpretation of ecgs cause difficulties for paramedics (13, 14). calling a specialized medical team to assist the paramedics in deciphering "difficult-to-analyze" ecg is economically and temporally unjustifiable. using the remote analysis and transmission systems of ecg at prehospital settings could be helpful in this regard. this study aimed to evaluate the accuracy of a remote analysis and transmission system of ecg in the prehospital this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. almukhambetova et al. 2 setting. 2. methods 2.1. study design and setting in this diagnostic accuracy study, the data of 19,265 ecgs of adult patients (aged ≥18 years) was gathered from ems database of almaty city, kazakhstan, from 2015 to 2019. all ecgs were recorded in the prehospital setting by a paramedic and using the "poly-spectrum" ecg recording device, and then remotely transmitted to the cardiologists. the findings of the automatically obtained analysis from the system were compared with the conclusions made by 19 experienced physicians working in the cardiology center (from 6 to > 30 years). the doctor previewed the ecgs and further excluded unnecessary artifacts performed by automatic analysis to achieve high accuracy of the final results. consequently, system and specialist reports were compared with each other. 2.2. about the system the system for remote analysis and transmission of ecg included the following parts: 12lead ecg registration, as well as transmitting devices that allow paramedic teams to share ecgs immediately after recording and monitor the patient’s condition during transportation to a medical institution. receiving and transmitting devices suitable for recording ecgs placed in the cardiology remote consultation point, on the emergency medical service (ems) station and the admission department of the city cardiology center. these devices help specialists to consult people and reach a syndromic conclusion in a couple of seconds online and by phone. moreover, specialists analyzed the ecgs in complicated clinical cases such as emergency hospitalization and thrombolytic therapy. they also provided advisory support and accurate recommendations to health professionals who transmitted the ecgs in order to monitor the patient at the prehospital setting. indications for using the mentioned system were as follows: the presence of clinical manifestations of acute coronary syndrome (unstable angina, heart attack) acutely formed life-threatening condition or hemodynamic disruption tachy/brady dysrhythmia in case of being unable to analyze ecgs on the scene 2.3. data gathering in this diagnostic accuracy study, the data of 19,265 ecgs of adult patients (aged ≥18 years) was gathered from ems database of almaty city, kazakhstan. all ecgs were recorded in prehospital setting by a paramedic and using the "polyspectrum" ecg recording device and then remotely transmitted to the cardiologists. consequently, they analyzed the ecgs to make the conclusion more exact. the results of the ecg analysis and recommendations were stored and registered in the surveillance log. 2.4. statistical analysis sensitivity, specificity, and accuracy were evaluated in order to establish the diagnostic capabilities of the tests. assessment and presentation of these indicators were carried out by calculating the 95% confidence interval using the statistical analysis package spss 13.0 for windows. 2.5. ethical considerations the research corresponded to declaration of helsinki, developed by the world medical association. permission or approval of the ethics committee was not required, because the publication describes a retrospective study, only a statistical analysis of available patient data was carried out. 3. results 19,265 ecgs were registered and stored in the database during the overall period of application. the average time from taking ecgs to receiving an expert’s conclusion was 9.2 ± 2.5 minutes. figure 1 shows a sample of transmitted ecg, diagnosis, and recommendation of specialist. the medical teams were called in 17.9% of cases after paramedic ecg recording; however, in the rest of the cases calling those teams was not required. the introduction of devices for recording and transmitting ecgs had its economic effect by reducing the number of visits of specialist teams. owing to that, 52,542,432 tenge (140000 $) was saved from being lost in vain only by 2016. 3.1. accuracy of ecg interpretation device according to the specialists’ interpretations, ecgs were analyzed to be normal in 16,992 (88.2%) patients (53% male) and had at least one abnormality in 7,086 (36.8%) cases. table one shows the frequency of ecg abnormalities and screening performance characteristics of the device in diagnosis of each abnormality. the overall sensitivity, specificity, and accuracy of ecg analysis device in diagnosis of ecg abnormalities were 83.8% (95%ci: 82.6 – 84.9), 95.5% (95%ci: 95.1 – 95.8), and 93.3% (95%ci: 92.9 – 93.7), respectively. 4. discussion based on the findings of the present study, the sensitivity, specificity, and overall accuracy of the automatic ecg analysis in the prehospital setting were 83.8%, 95.5%, and 93.3%, respectively. taking into consideration a review of previous studies on varthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e5 figure 1: example of a 73 years old patient’s ecg recorded by a paramedic in 12 leads and sent to a specialist. interpretation of ecg by "polyspectrum" recording device, which was confirmed by a specialist: sinus regular rhythm with a heart rate of 105 beats per minute; tachycardia; deviation of the electrical axis of the heart to the left; probably a lower myocardial infarction, the stage of scarring; possible anterior myocardial infarction, subacute stage; and left ventricular hypertrophy (lvh). the specialist recommended comparing it with previous ecgs and contrasting them with the symptoms and calling the intensive care team. table 1: sensitivity and specificity of the electrocardiogram (ecg) analysis device in diagnosis of different ecg abnormalities compared with cardiologist’s interpretation abnormality n (%) tp fp fn tn sensitivity specificity accuracy atrial fibrillation 1387 (7.2) 1311 607 76 17878 94,5 (93,2; 95,6) 96,7 (96,5; 97,0) 96,6 (96,3; 96,8) atrial flutter 139 (0.7) 108 56 31 19126 77,7 (70,1; 83,8) 99,7 (99,6; 99,8) 99,6 (99,5; 99,6) lvh 4527 (23.5) 3678 1353 849 14738 81,3 (80,1; 82,4) 91,6 (91,2; 92,0) 89,3 (88,9; 89,7) av block 559 (2.9) 473 195 86 18706 84,6 (81,4; 87,4) 98,9 (98,8; 99,1) 89,3 (88,9; 89,7) extra-systole 1888 (9.8) 1659 935 229 17377 87,9 (86,3; 89,3) 94,9 (94,6; 95,2) 94,2 (93,9; 94,6) rbbb 1522 (7.9) 1397 848 125 17743 91,8 (90,3; 93,1) 95,4 (95,13; 95,73) 95,2 (94,9; 95,5) lbbb 2639 (13.7) 2411 1258 228 16626 91,4 (90,2; 92,4) 92,9 (92,6; 93,3) 92,8 (92,4; 93,1) ischemia 1291 (6.7) 1168 489 123 17974 90,5 88,8; 92,0) 97,4 (97,1; 97,6) 96,9 (96,7; 97,1) lower mi 167 (6.8) 148 84 19 19098 88,6 82,9; 92,6) 99,6 (99,5; 99,6) 99,5 (99,4; 99,6) anterior-lateral mi 153 (0.9) 138 78 15 19112 90,2 (84,5; 94,0) 99,6 (99,5; 99,7) 99,5 (99,4; 99,6) sinus rhythm 16992 (88.2) 17817 283 782 1448 95,8 (95,5; 96,1) 83,7 (81,8; 85,3) 94,8 (94,5; 95,1) normal 12179 (63.2) 7439 2920 4740 11826 61,1 (60,2; 61,9) 80,2 (79,6; 80,8) 71,6 (71,0; 72,1) all measures are presented with 95% confidence interval. n: number; fp: false positive; fn: false negative; tp: true positive; tn: true negative; lvh: left ventricular hypertrophy; av: atrioventricular; rbbb: right bundle brunch block; lbbb: left bundle brunch block; mi: myocardial infarction. ious automatic ecg analysis programs by lyon, aurore et al., the sensitivity ranged from 75.9% to almost 100%, depending on the specific conclusion and method of electrocardiogram analysis (15). also, in the study of de chazal p. et al., the sensitivity was 75.9% for determining supraventricular extrasystoles, and 77.7% for ventricular extrasystoles (16). the diagnostic accuracy indicators for the blockage of the left leg of the his bundle, right bundle, extrasystole, atrial fibrillathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. almukhambetova et al. 4 tion, ventricular fibrillation, sinus node weakness syndrome, and normal ecg portrayed in a study by niwas et al., were near 99% (17). remote analysis and advisory support in making diagnostic and clinical decisions based on the interpretation of electrocardiograms help in using the practical clinical experience of highly qualified consultants where it is needed the most. during transportation to a medical facility, the program also allows monitoring of the patient’s condition and ensures that the medical facility is ready to receive a patient with an urgent condition, inasmuch as emergency revascularization in acute myocardial infarction. to record and decipher the ecg in an ordinary situation, the patient will have to get to an outpatient clinic or hospital, where the ecg will be further registered and analyzed. the great deal of effort, money, and time are required from the patient. as a result, the implementation of emergency care may be delayed. additionally, material costs for fuel and support of sanitary transport are also required to achieve the goal. with the introduction of a system for remote analysis of ecgs, all these problems are automatically solved, and it becomes possible to receive highly qualified diagnostic assistance in the conditions of the pre-hospital stage. besides, the direct economic effect of the mass introduction of ecgs recording and transmission devices is obvious, as the number of visits of specialized intensive care teams decrease. generally, during usage of remote ecg analysis, various problems occurred in about 0.3% of cases due to obtaining an "atypical" electrocardiogram (artifacts, etc.), which can be the result of incorrect positioning of the electrodes, patient’s muscle tremors, hardware errors, the performer’s inexperience, and software failures. as a consequence, reregistration and transmission of ecgs are often required in these cases. this method is recommended to be implemented in practical healthcare for early diagnosis and assistance, which can lead to an improvement in the health indicators of the population. 5. limitations as with any cross-sectional study, there was a risk of selection bias. the research was held at the particular region – almaty city (republic of kazakhstan). 6. conclusion the findings of this study showed the 93.3% accuracy of automatic ecg analysis device in interpretation of ecg abnormalities in prehospital setting compared with the cardiologist interpretations. using the device causes a decrease in the number of specialized intensive care teams’ visits. 7. declarations 7.1. acknowledgments the authors of the article express their sincere gratitude to the management and staff of the almaty ambulance service for their assistance in carrying out this work. 7.2. author contribution the contribution of each author is in the analytical search for scientific publications, writing the article and approving the content. 7.3. funding none. 7.4. conflict of interest no potential and actual conflicts of interest were present during our investigation. 7.5. availability of data the data of medical records of patients used in the publication are available only to healthcare workers of the republic of kazakhstan, who are working on the electronic resource of the complex medical information system called “damumed” (https://alm.dmed.kz/authentication/authentication/signin ?returnurl=%2f) references 1. smulyan h. the computerized ecg: friend and foe. the american journal of medicine. 2019;132(2):153-60. 2. guo s-l, han l-n, liu h-w, si q-j, kong d-f, guo f-s. the future of remote ecg monitoring systems. journal of geriatric cardiology: jgc. 2016;13(6):528-30. 3. bansal a, kumar s, bajpai a, tiwari v, nayak m, venkatesan s., et al. remote health monitoring system for detecting cardiac disorders. iet systems biology 2015;9(6):30914. 4. martinez-tabares f, costa-salas y, cuesta-frau d, castellanos-dominguez g. multiobjective design of wearable sensor systems for electrocardiogram monitoring. journal of sensors. 2016;2016:15. 5. gonzalez e, peña r, vargas-rosales c, avila a, de cerio d. survey of wbsns for pre-hospital assistance: trends to maximize the network lifetime and video transmission techniques. sensors. 2015;15(5):11993-2021. 6. yaakob n, khalil i. a novel congestion avoidance technique for simultaneous real-time medical data transmission. ieee journal of biomedical and health informatics. 2016;20(2):669-81. 7. ribeiro ah, ribeiro mh, paixão gmm, oliveira dm, gomes pr, canazart ja, et al. automatic diagnosis of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e5 12-lead ecg using a deep neural network. nature communcations. 2020;11(1):1760. 8. aljafar l, alotaiby t, al-yami r, alshebeili s, zouhair j, editors. classification of ecg signals of normal and abnormal subjects using common spatial pattern. 5th international conference on electronic devices, systems and applications (icedsa); 2016: institute of electrical and electronics engineers. 9. bonomini mp, ingallina fj, barone v, valentinuzzi me, arini pd, editors. comparison of electrocardiographic and vectorcardiographic planes on a set of left ventricular hypertrophy patients. vi latin american congress on biomedical engineering claib 2014, paraná, argentina 29, 30 & 31 october 2014; 2015 2015; cham: springer international publishing. 10. gregg r, zhou s, babaeizadeh s. can vectorcardiogram criteria unmask inferior q-waves in mason-likar 12-lead ecg? journal of electrocardiology. 2018;51(1):2-3. 11. said sa, bloo r, de nooijer r, slootweg a. cardiac and non-cardiac causes of t-wave inversion in the precordial leads in adult subjects: a dutch case series and review of the literature. world journal of cardiology. 2015;7(2):86100. 12. jonas de, reddy s, middleton jc, barclay c, green j, baker c, et al. screening for cardiovascular disease risk with resting or exercise electrocardiography: evidence report and systematic review for the us preventive services task force. jama. 2018;319(22):2315-28. 13. steinberg js, varma n, cygankiewicz i, aziz p, balsam p, baranchuk a, et al. 2017 ishne-hrs expert consensus statement on ambulatory ecg and external cardiac monitoring/telemetry. heart rhythm. 2017;14(7):e55e96. 14. mant j, fitzmaurice da, hobbs fd, jowett s, murray et, holder r, et al. accuracy of diagnosing atrial fibrillation on electrocardiogram by primary care practitioners and interpretative diagnostic software: analysis of data from screening for atrial fibrillation in the elderly (safe) trial. bmj. 2007;335(7616):380. 15. lyon a, mincholé a, martínez jp, laguna p, rodriguez b. computational techniques for ecg analysis and interpretation in light of their contribution to medical advances. journal of the royal society, interface. 2018;15(138):2017. 16. de chazal p, o’dwyer m, reilly rb. automatic classification of heartbeats using ecg morphology and heartbeat interval features. institute of electrical and electronics engineers transactions on biomedical engineering. 2004;51(7):1196-206. 17. niwas s i, selva kumari rs, sadasivam v. artificial neural network based automatic cardiac abnormalities classification: institute of electrical and electronics engineers; 2005. 41-6 p. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e17 or i g i n a l re s e a rc h the prevalence of personality disorders among emergency nurses based on mmpi-2 questionnaire; a crosssectional study parvin kashani1, sahar mirbaha2∗, mohammad mehdi forouzanfar2, farahnaz meschi3, alireza baratloo2 1. department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of clinical psychology, karaj branch islamic azad university, alborz, iran. received: may 2016; accepted: july 2016; published online: 9 january 2017 abstract: introduction: the prevalence of behavioral disorders is substantially higher in stressful working environments such as emergency departments. the present study aimed to evaluate the prevalence of personality disorders among emergency nurses. methods: in the present epidemiologic study, the prevalence of personality disorders among emergency nurses of three educational hospitals, tehran, iran, were evaluated based on minnesota multiphasic personality inventory-2 (mmpi-2) test. after the questionnaires were filled, data were entered to a special software for mmpi-2 test and the final result was interpreted based on the opinion of a clinical psychologist. findings were reported using descriptive statistics. results: 102 emergency nurses with the mean age of 30.2 ± 5.6 years were enrolled (100% female; 100% with master’s degree in nursing). the mean working time and experience of studied nurses were 210.8 ± 47.9 hours/month (130-370) and 4.1 ± 3.6 years (1-20), respectively. 32 (31.4%) cases showed symptoms of personality disorders the most common personality disorder detected in this study was somatization with 8.8%, hysteria with 6.9% prevalence, and pollyannaish with 4.9%. among the studied factors only recent history of unpleasant event has significant correlation with existence of personality disorders (p = 0.015). conclusion: the present study showed that somatization, hysteria, and pollyannaish were the most common personality disorders among the emergency nurses. history of an unpleasant event in the past year was the only effective factor in existence of personality disorders in the studied nurses. keywords: personality disorders; burnout, professional; workplace; nurses; emergency department © copyright (2017) shahid beheshti university of medical sciences cite this article as: kashani p, mirbaha s, forouzanfar m, meschi f, baratloo a. the prevalence of personality disorders among emergency nurses based on mmpi-2 questionnaire; a cross-sectional study. emergency. 2017; 5 (1): e17. 1. introduction workplace stress is one of the most important causes of mental illnesses as statistics show that one fourth of the employed population have experienced some kind of jobrelated behavioral disorder (1). the prevalence of these behavioral disorders is substantially higher in stressful working environments such as emergency departments (ed). the medical staff, especially nurses and physicians, are at risk of physical and mental damage in ed due to the ∗corresponding author: sahar mirbaha; department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. tel: +989121549505; email: mirsa317@yahoo.com nature of their work, which involves high work load, long working shifts with insufficient number of personnel, lack of social support, lack of free time for resting, and encountering serious injuries, wounds and adverse scenes (2). a systematic review in the past year has shown the 26-35% prevalence of personality and mental disorders among ed nurses due to their job (3, 4). these disorders not only affect the personnel’s health, but also decrease their efficiency and the quality of services they provide (5). meanwhile, the proper performance of hospital department personnel plays a major role in decreasing the burden caused by accidents and diseases, and increasing patient satisfaction (6, 7). existing studies have demonstrated the effect of job burnout on prevalence of behavioral disorders. however, findings reveal that in the same workplace environment, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 2 people are not affected by job burnout and personality disorders equally. in other words, personal, family-related and social factors all exert an effect on the prevalence of these disorders (8, 9). therefore, personality disorder is a multi-factorial condition, in which workplace stress, job burnout, and personal and social factors should be studied simultaneously. although numerous studies are available in the field of personality disorders caused by workplace stress, scarcity of such information in iran reveals the need for a study in this field. therefore, the present study was designed aiming to evaluate the prevalence of personality disorders among emergency nurses. 2. methods 2.1. study design and setting the present study is a cross-sectional one, in which nurses working in emergency departments of 3 hospitals, shohadaye tajrish, imam hossein and loghmane hakim, tehran, iran, were questioned in 2015. before asking the questions, written informed consent was obtained from all the nurses. the researchers adhered to the principles of helsinki declaration throughout the study. 2.2. participants the study population consisted of emergency nurses of the three mentioned educational hospitals. not giving consent and not filling out the questionnaire correctly and the questionnaire being invalid based on minnesota multiphasic personality inventory-2 (mmpi-2) test were considered as exclusion criteria. nurses were selected for questioning using simple random sampling. a list of nurses working at the hospitals was prepared for this purpose and participants were selected randomly. 2.3. data gathering personality disorders were evaluated based on the standard mmpi-2 test. mmpi-2 is a standard questionnaire for gathering a wide range of self-described characteristics and scoring them, which is a quantitative index of the individual’s emotional adaptability and shows their attitude toward taking part in the test (10). mmpi test is the most famous and widely used personality questionnaire that has been developed as an objective tool for diagnosis of mental diseases. this test is a self-evaluation questionnaire with “yes” or “no” answers and has 3 validity scales and 10 clinical scales. validity scales provide information regarding the subject’s approach to the test, while the 10 primary clinical scales are used for diagnosis of mental disorders. the most valuable use of mmpi-2 is in screening abnormal people generally and determining the severity of the problem specifically (11). diagnostic layers and scales of mmpi-2 include hypochondriasis, depression, hysteria, psychopathic deviate, masculinity/femininity, paranoia, psychasthenia, schizophrenia, hypomania, and social introversion. to increase the clinical benefit of mmpi, 3 validity scales are present including lie detection scale, infrequency, and defensiveness as correction or inhibition scale. demographic data and mmpi-2 test were included in a questionnaire, which was given to the studied nurses. 2.4. definitions recent unpleasant event was defined as any shocking tragic event during the previous year and recent trauma history was defined as any motor vehicle collision during the last year. 2.5. statistical analysis after the questionnaires were filled, data were entered to a special software for mmpi-2 test and the final result was interpreted based on the opinion of a clinical psychologist. data were analyzed via stata 11.0 statistical software and presented as mean ± standard deviation or frequency and percentage. 3. results: 104 emergency nurses were questioned, 2 cases were excluded due to unreliable questionnaires. finally, 102 participants with the mean age of 30.2 ± 5.6 years (23-49) were enrolled for analysis (100% female; 100% with master’s degree in nursing). 1 (1%) case had positive family history of known psychiatric disease. table 1 presents baseline characteristics of the studied cases. 52.9% of cases were married, 59.8% had stable employment status, 82.4% had variable work shifts, 71.4% earned ≥ 500 us dollars each month, 85.3% did not have any medical history, 86.3% did not have drug history, 33.3% had history of recent unpleasant event, and 4.9% had recent history of trauma. the mean working time and experience of the studied nurses were 210.8 ± 47.9 hours/month (130-370) and 4.1 ± 3.6 years (1-20), respectively. 32 (31.4%) cases showed symptoms of personality disorders based on mmpi-2 interpretations. table 2 shows the frequency of personality disorders among studied participants. the most common personality disorders detected in this study were somatization with 8.8%, hysteria with 6.9% prevalence, and pollyannaish with 4.9%. table 3 shows the relationship of demographic and baseline variables with personality disorders. among the mentioned factors, only recent history of unpleasant event had significant correlation with existence of personality disorders (p = 0.015). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e17 table 1: baseline characteristics of the questioned participants variable number (%) marital status married 54 (52.9) single 47 (46.1) divorced 1 (1) employment status stable 61 (59.8) unstable 41 (40.2) work shift day 7 (6.9) night 11 (10.8) variable 84 (82.4) income (us dollar/month) <500 29 (28.4) ≥500 73 (71.4) sole breadwinner yes 6 (5.9) no 96 (94.1) medical history yes 15 (14.7) no 87 (85.3) drug history yes 14 (13.7) no 88 (86.3) recent history of trauma yes 5 (4.9) no 97 (95.1) recent history of unpleasant event yes 34 (33.3) no 68 (66.7) table 2: frequency of detected personality disorders among studied emergency nurses based on mmpi-2 questionnaire disorders number (%) somatization 9 (8.8) hysteria 7 (6.9) pollyannaish 5 (4.9) depression 3 (2.9) reactive depression 2 (2.0) schizopora 2 (2.0) hypochondriasis 2 (2.0) shy 1 (1.0) anxiety 1 (1.0) 4. discussion: the present study showed that somatization, hysteria, and pollyannaish were the most common personality disorders among the studied nurses. history of recent unpleasant event in the past year was the only effective factor in existence of personality disorders in the studied nurses. the prevalence of personality disorders in the general population has been reported to be 4.4 10% (12-14). however, the rate is much higher among the participants of this study (31.4%). it should not be overlooked that some personality disorders remain hidden and symptoms only show when the individual is under workplace stress. mealer et al. reported 18% more anxiety and 11% higher depression rates in intensive care unit (icu) nurses compared to the general population (29% more in total) (15). in the present study, prevalence of anxiety and depression were 1% and 4.9%, respectively. in this study, nurses were selected from emergency departments. exposure of the nurses to death scenes and dying patients for a long time can take a toll on their mental wellbeing (15). this is backed up by the findings of a study that showed emotional responses and psychophysiologic outcomes are more severe in nurses who have witnessed death and serious injuries in comparison with others and therefore, individuals in this group are more prone to post-traumatic stress disorders (16). in contrast, escriba-aguir et al. showed that there is no evidence that workplace and workload negatively impact presentation of burnout syndrome (2). however, yong et al. measured saliva cortisol and expressed that ed nurses have higher stress levels compared to nurses from other departments. they concluded that ed nurses are under more stress but this does not increase the risk of having mental diseases (17). in other words, ed nurses’ ability to adapt to stress might have prevented them from developing personality disorders and showing symptoms. psychological resilience is a factor affecting mental disorders (15). presence of psychological resilience results in a significant decrease in the prevalence of post-traumatic stress disorder, burnout syndrome and symptoms of depression and anxiety. therefore, resilience is a defense mechanism that can increase the ability of the nurses and other medical staff to adapt to workplace stresses. since this mechanism is acquisitive, training programs to upgrade the skills of the treatment staff regarding psychological resilience can decrease the symptoms of mental and personality disorders, and increase job satisfaction (15). environmental stressors are among the factors leading to mental and personality disorders (18, 19). the findings of this study also showed that history of recent unpleasant event in the past year is an independent factor that exerts an effect on the existence of personality disorders in nurses. nevertheless, to reach a conclusion in this regard, more studies with proper design are needed. one of the limitations of this study was its low sample size, which may influence the power of the study. the nature of evaluating personality disorders is another limitation of this study. in most cases, personality disorders are not a single problem and several diagnoses are made for an individual. therefore, it is possible that the reported percentages are different from reality to some extent. in addition, the psychologist who makes the diagnosis also plays a role. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 4 table 3: the relationship of baseline characteristics of the studied population with personality disorders variable personality disorders p value absent present age (year) 30.1 ± 5.6 30.4 ± 5.7 0.808 mean working (hours/month) 212.8 ± 51.8 206.6 ± 38.4 0.122 mean working experience (years) 4.0 ± 3.4 4.3 ± 4.1 0.234 marital status single 31 (44.3) 16 (50) 0.709 married 38 (54.3) 16 (50) divorced 1 (1.4) 0 (0) employment status unstable 10 (19.6) 5 (20) 0.597 stable 41 (80.4) 20 (80) working shift type day 4 (5.7) 3 (9.4) 0.720 night 7 (10) 4 (12.5) variable 59 (84.3) 25 (78.1) income (us dollars/month) < 500 19 (27.1) 10 (31.3) 0.420 ≥ 500 51 (72.9) 22 (68.8) sole breadwinner no 64 (91.4) 32 (100) 0.097 yes 6 (8.6) 0 (0) medical history no 61 (87.1) 26 (81.3) 0.309 yes 9 (12.9) 6 (18.8) drug history no 62 (88.6) 26 (81.3) 0.242 yes 8 (11.4) 6 (18.8) recent history of unpleasant event no 52 (74.3) 16 (50) 0.015 yes 18 (25.7) 16 (50) recent history of trauma no 68 (97.1) 29 (90.6) 0.176 yes 2 (2.9) 3 (9.4) data were presented as mean ± standard deviation or number and percentage. 5. conclusion: the present study showed that somatization, hysteria, and pollyannaish were the most common personality disorders among the emergency nurses. history of a recent unpleasant event in the past year was the only effective factor in existence of personality disorder in the studied nurses. 6. appendix 6.1. acknowledgements we would like to express our special thanks to ms. mahnaz nikpeyma who kindly helped us in performing this study. 6.2. authors contribution all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data collection and interpretation. 6.3. conflict of interest all authors declare that there is no conflict of interest in this study. 6.4. funding this study was conducted with a grant from the clinical research development center of loghmane hakim hospital. this study was a part of dr. sahar mirbaha’s thesis for emergency medicine residency at shahid beheshti university of medical sciences, tehran, iran. references 1. kessler rc, demler o, frank rg, olfson m, pincus ha, walters ee, et al. prevalence and treatment of mental disorders, 1990 to 2003. new england journal of medicine. 2005;352(24):2515-23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e17 2. escriba-aguir v, martin-baena d, perez-hoyos s. psychosocial work environment and burnout among emergency medical and nursing staff. international archives of occupational and environmental health. 2006;80(2):127-33. 3. adriaenssens j, de gucht v, maes s. determinants and prevalence of burnout in emergency nurses: a systematic review of 25 years of research. international journal of nursing studies. 2015;52(2):649-61. 4. forouzanfar mm, alitaleshi h, hashemi b, baratloo a, motamedi m, majidi a, et al. emergency nurses job satisfaction and its determinants. journal of shahid beheshti school of nursing & midwifery. 2013;23(80). 5. visser mr, smets em, oort fj, de haes hc. stress, satisfaction and burnout among dutch medical specialists. canadian medical association journal. 2003;168(3):2715. 6. laschinger hks, leiter mp. the impact of nursing work environments on patient safety outcomes: the mediating role of burnout engagement. journal of nursing administration. 2006;36(5):259-67. 7. baratloo a, maleki m. iranian emergency department overcrowding. journal of emergency practice and trauma. 2015;1(2):39. 8. garrosa e, moreno-jimenez b, liang y, gonzãąlez jl. the relationship between socio-demographic variables, job stressors, burnout, and hardy personality in nurses: an exploratory study. international journal of nursing studies. 2008;45(3):418-27. 9. garrosa e, rainho c, moreno-jimenez b, monteiro mj. the relationship between job stressors, hardy personality, coping resources and burnout in a sample of nurses: a correlational study at two time points. international journal of nursing studies. 2010;47(2):205-15. 10. butcher jn. minnesota multiphasic personality inventory. corsini encyclopedia of psychology. 1989. 11. temple r. minnesota multiphasic personality inventory. encyclopedia of clinical neuropsychology: springer; 2011. p. 1629-32. 12. lenzenweger mf. epidemiology of personality disorders. psychiatric clinics of north america. 2008;31(3):395-403. 13. grant bf, chou sp, goldstein rb, huang b, stinson fs, saha td, et al. prevalence, correlates, disability, and comorbidity of dsm-iv borderline personality disorder: results from the wave 2 national epidemiologic survey on alcohol and related conditions. the journal of clinical psychiatry. 2008;69(4):533. 14. coid j, yang m, tyrer p, roberts a, ullrich s. prevalence and correlates of personality disorder in great britain. the british journal of psychiatry. 2006;188(5):423-31. 15. mealer m, jones j, newman j, mcfann kk, rothbaum b, moss m. the presence of resilience is associated with a healthier psychological profile in intensive care unit (icu) nurses: results of a national survey. international journal of nursing studies. 2012;49(3):292-9. 16. carson ma, paulus la, lasko nb, metzger lj, wolfe j, orr sp, et al. psychophysiologic assessment of posttraumatic stress disorder in vietnam nurse veterans who witnessed injury or death. journal of consulting and clinical psychology. 2000;68(5):890. 17. yang y, koh d, ng v, lee fcy, chan g, dong f, et al. salivary cortisol levels and work-related stress among emergency department nurses. journal of occupational and environmental medicine. 2001;43(12):1011-8. 18. xue c, ge y, tang b, liu y, kang p, wang m, et al. a meta-analysis of risk factors for combat-related ptsd among military personnel and veterans. plos one. 2015;10(3):e0120270. 19. jahn dr, poindexter ek, cukrowicz kc. personality disorder traits, risk factors, and suicide ideation among older adults. international psychogeriatrics. 2015;27(11):178594. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e17 https://doi.org/10.22037/aaem.v9i1.1063 ca s e re p o rt rare and underestimated association of pulmonary embolism and olanzapine therapy; report of two cases hammam rasras1∗, mustapha beghi1, maryem samti1, nabila ismaili1,2, noha el ouafi1,2 1. department of cardiology, mohammed vi university hospital of oujda, mohammed first university of oujda, morocco. 2. laboratory of epidemiology, clinical research and public health, faculty of medicine and pharmacy, mohammed the first university of oujda, morocco. received: december 2020; accepted: december 2020; published online: 5 february 2021 abstract: venous thromboembolic disease (vtd) is a very common and severe pathological condition in which there are many predisposing factors. olanzapine is a drug frequently used in psychiatric practises; it is thought to increase the risk of vtd. here, we report two cases, a young man and a woman, with a medical history of schizophrenia treated by olanzapine who developed pulmonary embolism and we did not find any aetiologies of vtd in them. due to the link between olanzapine and pulmonary embolism, which has been previously described, olanzapine is considered responsible for this problem. two mechanisms have been reported in the literature in this regard; significant weight gain and lethargy, which are very common side effects of olanzapine. so far, no direct effect of olanzapine on platelet aggregation or coagulation has been found. in patients developing vtd while being treated with olanzapine, discontinuation of olanzapine as a treatment option must be done with an adjustment of antipsychotic treatment and regular monitoring of psychic symptoms. since the diagnosis of pulmonary embolism is not easy to make in a schizophrenic patient, clinicians should take that in consideration when prescribing these drugs and when facing clinical situations where vtd is suspected. keywords: pulmonary embolism; venous thromboembolism; risk factors; antipsychotic agents; olanzapine cite this article as: rasras h, beghi m, samti m, ismaili n, el ouafi n. rare and underestimated association of pulmonary embolism and olanzapine therapy; report of two cases. arch acad emerg med. 2021; 9(1): e17. 1. introduction venous thromboembolic disease (vtd) is a multifactorial disease, which is represented by two entities: deep venous thrombosis (dvt) or pulmonary embolism (pe). vtd usually develops due to many thromboembolic risk factors, such as old age, context of immobilization, post-surgery or pregnancy, past history of dvt, neoplasia, certain drugs (oestrogens, chemotherapy), antiphospholipid syndrome, obesity, sedentarily, and hypercoagulability states, including mutation of factor v leiden or prothrombin (1). like many diseases, vtd has predisposing factors, which are grouped into three categories, termed the virchow’s triad: endothelial injury, stasis of blood flow, and, hypercoagulability (2). it is a major cause of morbidity and mortality among hospitalized patients, with an annual incidence of 1 per 1000 population ∗corresponding author: hammam rasras; department of cardiology, mohammed vi university hospital of oujda, mohammed first university of oujda, morocco. tel: 00212762675885, email: h.rasras@hotmail.com, orcid: https://orcid.org/0000-0002-7575-9404 (3). olanzapine is an atypical antipsychotic (aap) (secondgeneration antipsychotic), prescribed for schizophrenic patients, especially those with positive symptoms. this therapeutic class has several side effects, including metabolic syndrome and diabetes, hyperprolactinemia, sexual dysfunction, and weight gain (4), which is more frequently observed in olanzapine. the incidence of vtd in aap users is increased by 2.20 (95% ci: 1.22-3.95) times (3). we report two cases, a young man and a woman with a history of paranoid schizophrenia, who presented with pe while using olanzapine without inherited risk factors for vtd. we further explored the possible association between olanzapine and vtd. lastly, we took a brief look at and reviewed the potential mechanisms behind this association. 2. cases presentation 2.1. case 1 a 28-year old male patient, with no risk factors for vtd, with a medical history of schizophrenia on olanzapine therapy, was admitted for an acute onset of hallucinations and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. rasras et al. 2 figure 1: axial cut of thoracic computed tomography angiography showing embolism in right and left pulmonary artery. delirious behaviour with dyspnoea. on admission, he was confused, afebrile, had tachycardia with a blood pressure at 130/50mmhg and normal oxygen saturation in room air. cardiovascular, respiratory, and abdominal examinations’ findings were insignificant. there were no signs of meningism. blood tests revealed high d-dimer (7.11µg/l), troponin (2928 ng/l) and b-type natriuretic peptide (bnp) (2415 pg/m) levels. chest x-ray showed an elevation of the right dome of diaphragm with low abundance pleurisy, whilst his electrocardiogram (ecg) showed sinus tachycardia and right bundle branch block with a right axis deviation. computed tomography (ct) pulmonary angiogram revealed an extensive right and left pulmonary embolism (figure 1). systolic pulmonary arterial pressure (spap) was 41 mmhg, paradoxical septum, and dilated right ventricle (rvd/vg = 1.14) with systolic dysfunction were observed in the transthoracic echocardiography (tte). the simplified pulmonary embolism severity index (s-pesi) was 1 and the patient was classified as a high intermediate risk patient. in etiological assessment: doppler ultrasound of two legs, tests for thrombophilia (no family history of thrombophilia was found), tumor markers, and thoracic, abdominal, and pelvic ct angiography showed no abnormalities. all of the diagnostic tests were normal, and since the only possible risk factor was olanzapine therapy, it was terminated after psychiatric consultation, and then he was put on aripiprazole. then, he was treated with anticoagulants. 2.2. case 2 a 68-year old female patient, obese with a medical history of psychotic depression on olanzapine therapy, was admitted for an atypical chest pain and dyspnoea. on admission, she was asthenic, had no fever, heart rate was 111 beats/minute, blood pressure was 100/50 mmhg, and respiratory rate was 28 cycles/minute. her oxygen saturation level was low (90 % in room air). physical examination findings were insignificant. blood tests revealed high d-dimer (1.88 µg/l), troponin (7439 ng/l) and bnp (1324 pg/m) levels. chest x-ray was normal, ecg showed sinus tachycardia. ct pulmonary angiography revealed a bilateral extensive pulmonary embolism (figure 1). tte showed a dilated right ventricle with systolic dysfunction and a systolic pulmonary arterial pressure (spap) at 64 mmhg. the s-pesi was 2 and the patient was classified as a high intermediate risk patient. in etiological assessment: doppler ultrasound of two legs, tumor markers, gynaecological examination, mammography, and thoracic, abdominal and pelvic ct angiography revealed no anomalies. then, she was put on heparin therapy with relay by vitamin k antagonist until the repeated international normalized ratio (inr) was between 2 and 3. heparin was stopped on the 9th day, with good evolution. 3. discussion vtd is a complex disease, involving interaction between acquired or inherited predispositions to thrombosis (thrombophilia) and environmental exposures (clinical risk factors). many studies have considered olanzapine as a risk factor that might increase the risk of vtd. this presentation was reported for the first time in germany in 1950s (4). the underlying mechanism is still unknown. in our study, we are trying to take a brief look at literature and review the hypotheses of the potential mechanisms behind this association. some clinical and pharmacological studies have been published in this domain, trying to explain the causality of this association between olanzapine and vtd. in 2002, hagg et al. (5) found an increased level of antiphospholipid antibodies and hyperprolactinemia in patients on olanzapine therapy, and then considered it as an independent risk factor for thromboembolic events. in 2008, kannan et al. reported six cases of fatal pe in six patients who were on olanzapine therapy for a long period; they showed that olanzapine binds to serotonin receptors, and then activates serothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e17 tonergic system, which stimulates platelet aggregation; it can also bind to alpha-receptors, which contributes to the formation thrombosis by causing hypotension and venous blood stasis (1). some hypotheses were proposed by these two teams and it was suggested that olanzapine can induce hyperleptinemia, which might lead to abnormalities in fibrinolysis, as well as metabolic disorders, such as dyslipidaemia and hyper-homocysteinemia, which play an important role in thrombotic events (1, 5). a retrospective study on the who database showed that vtd occurred with a higher frequency in patients on olanzapine and clozapine compared to those on other aaps, and in 60% of cases this event occurred within the first 3 months of treatment. moreover, like other studies, some plausible mechanisms were suggested; such as antipsychotic-induced sedation, obesity, hyperleptinemia, the presence of antiphospholipid antibodies, and enhanced platelet aggregation (6). in 2018, a study was performed by the netherlands. pharmacovigilance centre lareb on seventeen patients who developed vtd while using olanzapine, and only a few of them had thromboembolism risk factors. this study showed a higher incidence rate of vtd in patients on aap therapy compared with populations who had predisposing factors of vtd, and that like other mentioned studies was explained by the drug’s side effects, causing platelet aggregation and inducing the blockade of histamine-1 receptor and α-1 receptor. it has also been shown that olanzapine and clozapine have the most profound impact compared to other aaps. moreover, discontinuation of olanzapine has been suggested for those who develop vtd, with a control of psychotic symptoms and antipsychotic treatment options (3). a pharmacological study performed by almuqdadi et al. has confirmed that olanzapine could antagonise the serotonin (5-ht2a) receptors; since these receptors are present on platelets, olanzapine is thought to be a factor influencing platelet aggregation (7). other studies were performed in the same domain trying to explain the mechanism behind this association, for instance, carrizo et al. found increased leptin and plasminogen activator inhibitor-1 (pai-1) levels in patients treated with olanzapine, and believed that this makes them more exposed to thromboembolic events (8). both the dutch website for drug information ‘farmacotherapeutischkompas’ and the dutch summary of product characteristics (smpc) indicated that there is no direct relationship between olanzapine and vtd and that the underlying cause of vtd are the side effects induced by olanzapine (9, 10). in our cases, no risk factor of vtd was found in the first patient and etiological assessment did not reveal any abnormalities for any of the patients, and we believe that olanzapine is the underlying cause of pe, similar to the previously reported cases. no validated risk assessment score is available for identification of psychiatric patients who might benefit from pharmacological vtd prophylaxis, and we are looking forward to performance of studies that can establish a scoring system for evaluating the risk of thromboembolic events before initiation of therapy with olanzapine or other aaps. 4. conclusion olanzapine is an increasingly prescribed drug for patients with schizophrenia, and like all other drugs, it has side effects that can be banal or potentially serious and life threatening. the incidence rate of vtd in patients treated with olanzapine is higher than that of the general population, and despite the absence of studies that confirm the direct link between them, olanzapine is considered to be a factor that can increase the risk of thromboembolic events. further studies, especially pharmacological studies that can confirm the underlying cause and find prophylactic treatments, especially for patients who already have thromboembolic risk factors, should be considered. 5. declarations 5.1. acknowledgements none. 5.2. authors contribution all authors passed the criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. ethical consideration the authors adhered to confidentiality of patients’ profiles and ethical recommendations regarding research in biomedical field. 5.4. conflict of interest the authors declare that there is no conflict of interest regarding this study. 5.5. source of financial support no financial support was received for this study. references 1. kannan r, molina dk. olanzapine: a new risk factor for pulmonary embolus? the american journal of forensic medicine and pathology. 2008;29(4):368-70. 2. esmon ct. basic mechanisms and pathogenesis of venous thrombosis. blood reviews. 2009;23(5):225-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. rasras et al. 4 3. dijkstra m, van der weiden c, schol-gelok s, mullerhansma a, cohen g, van den bemt p, et al. venous thrombosis during olanzapine treatment: a complex association. the netherlands journal of medicine. 2018;76(6):263-8. 4. grahmann h. thombose hazard in chlorpromazine and reserpine therapy of endogenous psychosis. nervenarzt. 1959;30:224-5. 5. hagg s, spigset o. antipsychotic-induced venous thromboembolism. cns drugs. 2002;16(11):765-76. 6. hagg s, bate a, stahl m, spigset o. associations between venous thromboembolism and antipsychotics. drug safety. 2008;31(8):685-94. 7. almuqdadi a, bulatova n, yousef a-m. the effect of atypical antipsychotics on platelet aggregation. open journal of hematology. 2016;7(1). 8. carrizo e, fernandez v, quintero j, connell l, rodriguez z, mosquera m, et al. coagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free firstdegree relatives. schizophrenia research. 2008;103(13):83-93. 9. nederland z. farmacotherapeutischkompas [available from: https://www.farmacotherapeutischkompas.nl/. 10. dutch smpc olanzapine zalasta 2.5/5/7.5/10/15/20 tablets 2012 [26 july 2012:[available from: https://www.ema.europa.eu/en/documents/productinformation/zalasta-epar-product-information_nl.pdf. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction cases presentation discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e44 or i g i n a l re s e a rc h optimization of service process in emergency department using discrete event simulation and machine learning algorithm sayyed_morteza hosseini_shokouh1,2, kasra mohammadi3, maryam yaghoubi1∗ 1. health management research center, baqiyatallah university of medical sciences, tehran, iran. 2. faculty of health, baqiyatallah university of medical sciences, tehran, iran. 3. industrial management department, allame tabataba’i university, tehran, iran. received: march 2022; accepted: may 2022; published online: 8 june 2022 abstract: introduction: emergency departments are operating with limited resources and high levels of unexpected requests. this study aimed to minimize patients’ waiting time and the percentage of units’ engagement to improve the emergency department (ed) efficiency. methods: a comprehensive combination method involving discrete event simulation (des), artificial neural network (ann) algorithm, and finally solving the model by use of genetic algorithm (ga) was used in this study. after simulating the case and making sure about the validity of the model, experiments were designed to study the effects of change in individuals and equipment on the average time that patients wait, as well as units’ engagement in ed. objective functions determined using artificial neural network algorithm and matlab software were used to train it. finally, after estimating objective functions and adding related constraints to the problem, a fractional genetic algorithm was used to solve the model. results: according to the model optimization result, it was determined that the hospitalization unit, as well as the hospitalization units’ doctors, were in an optimized condition, but the triage unit, as well as the fast track units’ doctors, should be optimized. after experiments in which the average waiting time in the triage section reached near zero, the average waiting time in the screening section was reduced to 158.97 minutes and also the coefficient of units’ engagement in both sections were 69% and 84%, respectively. conclusion: using the service optimization method creates a significant improvement in patient’s waiting time and stream at emergency departments, which is made possible through appropriate allocation of the human and material resources. keywords: efficiency; emergency service, hospital; operations research; patients cite this article as: hosseini_shokouh sm, mohammadi k, yaghoubi m. optimization of service process in emergency department using discrete event simulation and machine learning algorithm . arch acad emerg med. 2022; 10(1): e44. https://doi.org/10.22037/aaem.v10i1.1545. 1. introduction hospital is one of the most important sectors of healthcare and the emergency department (ed) is considered as one of the most critical and crowded departments of hospitals (1). hospitals’ managers are constantly trying to control rising costs, while responding to the growing demand for health care. as a result, they need to regularly review the efficiency of eds to find opportunities for improvement (2). high re∗corresponding author: maryam yaghoubi; nosrati alley, south sheykhbahaee ave., mollasadra ave., vanak square, tehran, iran. po box. 14359164471, email: yaghoobbi997@gmail.com, tel: +982187555474, orcid: http://orcid.org/0000-0002-2138-4205. ferral rate and limited resources (physician, nurse, etc.) have clarified the importance of optimization methods in the process of evaluation and resource utilization in the health system, and specifically in eds (3). the number of patients who refer to eds has a steadily growing trend. there was a 30% growth in ed visits in france from 2002 to 2012. eds were one of the most crowded departments of a hospital during the covid-19 pandemic and played a very important role in therapeutic response to the covid-19 pandemic (4, 5). the elderly, limited access to medical care from other resources, and the high rate of use of eds for non-emergency care are the main factors leading to the growing number of patients in the eds (6). the development of health infrastructures and appropriate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. hosseini_shokouh et al. 2 allocation of resources will play a very important role in the implementation of general health policies (7). in the case of healthcare organizations, the improvement efforts, and thus the decisions, are concentrated on a system that aims to provide high-quality care, appropriate service times, and is also efficient in the use of resources. however, designing and operating these systems, especially eds, are extremely complicated, mainly due to the high number of different resources involved in the activities of providing care, the uncertainty resulting from these activities happening at different moments, and the distinguished probability of simultaneously requiring resources (8). as a result, long patient waiting times and overcrowding are common problems in eds all over the world. optimization of patients’ stream and bottleneck elimination in the ed could provide a solution that lessens the cost and raises the quality of care (4). designing an appropriate allocation plan for human and material resources should be considered as one of the most important tasks in eds. in this context, simulation and optimization techniques have been used to address the described management problems in a complicated healthcare system (10)(11)(12). most of these works do not pay attention to all stages of a patient stream in the ed. in order to respond to this gap, this study aimed to simulate an optimal patient stream in ed to reduce patient waiting time as well as raise the percentage of resource employment to an optimal level. 2. methods 2.1. study design and setting the present study was a longitudinal and simulation study conducted from 21 march 2019 to 19 february 2020. the optimization method used in this research is a combination of comprehensive methods involving discrete event simulation (des), artificial neural network (ann) algorithm, and finally solving the model by use of genetic algorithm (ga). the main objectives of the model include reducing the patients’ waiting time and increasing the percentage of resources deployed to make optimal use of them. these two objectives will be modeled as two objective functions. the number of physicians, nurses, hospital beds, and triage space were considered as variables in the objective function. the research steps of work, as shown in figure 1, were data collection, simulating the systems’ current status using des, validation of the simulated model, implementation of experiment design, ann training and achieving system changes, modelling the problem, solving the model, and studying the outcome. 2.2. data gathering data needed for workflow simulation were collected through observation by 2 researchers during 11 months. all the patients (74,796 patients) who referred to ed from 21 march 2019 to 19 february 2020 (11 months) were recorded and investigated by researchers using the census method. a summary of the number of studied patients in each part of ed is presented in (table 1). 2.3. developing the model the relation between different parts in the emergency department was registered through observation of ed workflow. after collecting information and data regarding processes using enterprise dynamics software, the model was simulated. enterprise dynamics software is an objectiveoriented simulation, which is combined with an eventdriven method. first, using an auto-fit menu, the probability distribution of data related to patients’ entry rate and service entry was determined. after determining the probable functions, the simulation model was designed. the next stage in simulation was to make sure about the accuracy and validity of the simulated model. 2.4. validation of model in the validation process, the average of the real and simulated data was studied through an independent t-test at the confidence level of 95%. in the next step, the current status of the service system regarding the queue length criterion was examined to identify the crowded sections that need improvement. finally, machine learning experiments were designed to examine the effect of changes in individuals and equipment on average patient waiting time as well as the engagement rate of the units. in this regard, the complete factorial method was utilized by considering the central and axis points as well as 3 replications in minitab software. after designing the experiments and implementing them on the simulated model, as well as determining the queue length and the percentage of the units’ engagement, artificial neural network (ann) and fractional genetic algorithm (ga) were used for simulation using matlab 2016 software. in this article, we have omitted the details and writing of mathematical models and syntax of the algorithms used and tried to clarify its management results for the reader. it should be noted that for ease of reading, the table of columns related to the minitab executive operation and its prioritization has been omitted. 2.5. designing the model the effect of 4 factors or resources on the system output were measured: the number of triage operators (triage), fast track physicians, ed physicians, and the number of inpatient beds (hospitalization) . all 4 factors have a queue and need to be examined in more detail. after designing the experiments, each of the experiments had been simulated and the related information was recorded in table 3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e44 table 1: number of patients in each part of the studied emergency department during the study period number month 1 2 3 4 5 6 7 8 9 10 11 non-hospitalized futile cases 3 1 6 2 2 4 3 3 1 5 2 outpatients 4154 4578 4268 4065 3935 4085 4603 4450 4382 4431 4925 hospitalized cases ed 2465 2660 2518 2481 2524 2490 2485 2430 2287 2298 2250 general ward 516 509 600 810 899 803 799 844 748 730 670 special ward 132 114 136 116 125 146 121 137 124 154 151 others dama 146 169 172 147 147 156 147 159 138 102 119 dispatched1 4 3 5 4 3 5 4 3 4 3 9 died (first 24 h) 9 11 8 7 9 9 8 7 8 4 5 discharged2 (%6 h) 74 71 66 66 68 67 66 67 65 67 65 discharged3 (%12 h) 14 10 12 13 11 11 13 11 17 12 9 total 6622 7239 6792 6548 6461 6579 7091 6883 6670 6734 7177 ed: emergency department; dama: discharged against medical advice; h: hour. 1 : to other hospitals; 2 : percentage of discharged cases within 6 hours. 3 : percentage of discharged cases within 12 hours. table 2: the mean waiting times of patients in different sections of the studied emergency department (ed) waiting time (hours) mean ± sd min max 95% ci triage unit 139.72 ± 56.14 103.87 351.69 124.16155.29 fast track unit 5158.57 ±1747.36 2486.89 10349.52 4673.98 5643.16 ed specialist 458.21 ±61.96 366.13 634.32 441.02 -475.39 hospitalization 57.03 ±41.35 3.35 166 45.56 -68.5 sd: standard deviation. ci: confidence interval. min: minimum, max: maximum. 2.6. validation checking the validity of the model shows that the simulated model was not statistically different from the real data (p = 0.356). after ensuring the validity of the model, experiments were designed to investigate the effects of changes in the number of personnel and equipment in the emergency department on the average waiting time of patients and the percentage of bed occupancy. 2.7. optimization according to the model optimization result, it was determined that the hospitalization unit, as well as the hospitalization units’ doctors, were in an optimized condition, but the triage unit, as well as the fast track units’ doctors, should be optimized. according to the resulting optimized answer, the changes in patients’ average waiting time, as well as units’ efficiency coefficient were as follows (table 4). the average waiting time in the triage unit was reduced to almost zero, also, the average waiting time in the fast track section was reduced to 158.97 minute. units’ engagement percentage in the two mentioned sections was 69% and 84%, respectively. although the unit engagement percentage was reduced, this slight reduction can be overlooked due to the significant improvement in patients’ waiting time. 3. results the studied ed’s workflow is presented in figure 2. the studied ed included different parts. ed physician was in charge of patients who needed critical cares. fast track phycisian was in charge of patients who needed fewer emergency services. after entering the ed, patients go to the triage section to be categorized into 5 levels based on their medical conditions. in this section, patients who are considered as level 1 and 2 are handed over to the ed physician. the ed physician sends them to recovery, hospitalization, or outpatient service parts. level 3 patients are assigned to both ed and fast track physicians. levels 4 and 5 patients are assigned to the fast track physician. the mean waiting times in different sections of the ed were calculated and presented in table 2. 4. discussion the decision-making process is extremely challenging for ed managers. therefore, offering them the possibility to acquire more knowledge and evidence to ease this process is extremely valuable, especially in eds where poor decisions may lead to critical situations for patients. in this research, in contrast to traditional methods like regression, to estimate the objective function, trained networks this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. hosseini_shokouh et al. 4 figure 1: research implementation steps. were utilized. the results show the good performance of the proposed method in the analysis and optimization of the system. the major goals of this research are reducing the patients’ waiting time as well as increasing the units’ engagement percentage for optimal usage, which are modeled as the two objective functions. after collecting the information and processes by use of ed software, the model was simulated to include the system complexities in the model. after making sure about the model validity, the experiments were designed to examine the effects of changes in sectors’ individuals and equipment on the average patient waiting time as well as the units’ engagement percentage. in the study by duguay et al. (13), some alternatives, based on adding resources, have been investigated to reduce pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e44 figure 2: the relation between different parts in the emergency department. tient waiting times and to improve overall service delivery and system’s throughput. additionally, thorwarth et al. (14), examined the impact of staff scheduling on overall utilization and burnout issues related to overutilized staff. considering the reviewed literature, some important performance measures such as resource utilization, productivity, and lay-out efficiency have not been analyzed completely, also there is a lack of a link between these indicators and international standards. kırış et al. (15), developed a knowledge-based reactive scheduling system for emergency departments. to minimize patient waiting time, they considered patients’ priorities, arrival time, flow time, and physician’s workload. in a similar study azadeh et al. (16) proposed a genetic algorithm (ga) for solving the problem of scheduling prioritized patients in emergency department laboratories. a response surface methodology (rsm) is applied for tuning the ga parameters. the algorithm can significantly improve the efficiency of the emergency department by reducing the total waiting time of prioritized patients. granja et al. (17) proposed a simulation-based optimization approach to the patient admission scheduling problem to minimize patients’ length of stay, while reducing the costs and increasing (or at least maintaining) the quality of care. the number of studies applying simulation for the improvement of healthcare systems has increased since the early 1990s, (18). simulation studies within eds have been used to improve the performance and reduce patients’ waiting time by studying multiple scenarios such as growing the number of physicians, staff, and medical devices (12). gunal et al. (19), analyzed how to increase emergency department performance through discrete-event simulation. in a similar study, al-refaie et al. (12), took advantage of simulation in a jordanian hospital’s ed to decrease the average patient waiting time, increase the number of served patients, and improve nurses’ productivity. finally, they claimed that flexibility in cellular service systems such as hospitals has played an important role in improving the performance of ed. zeng et al. (20) have done a study to increase the quality of services in a hospital’s ed in kentucky, using computer simulation. they considered the length of stay, waiting times, and patient elopement as the most important parameters. according to our study results, the optimization of the patient stream at ed is possible through appropriate allocation of the human and material resources. azadeh et al. (1) also optimized the process of work in the ed of a hospital in iran by taking advantage of simulation optimization and modeling human errors. repeated venipuncture, unsafe transportation, and sampling errors were considered in that study. norouzzadeh et al. (21), developed a modular discrete event simulation in a hospital’s ed to simplify the process of patient flow to inpatient wards. finally, the result showed that in order to make sure about better efficiency in ed, all of the improvements should be accomplished at the same time. 5. limitations the present study, like other studies, had limitations that we like to mention here. first, multi-criterion decision-making methods about system optimization policies were not considered in the present study, but can be included in the model in future studies. second, the study result is based on the studied patients’ features and circumstance; therefore, the effect of covid-19 pandemic on the ed had not been considered in this study, the consideration of which in future studies will be helpful. since ed waiting time and other indicator data were not this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. hosseini_shokouh et al. 6 table 3: results of the designed experiments (different modes of resource utilization) row number of sources waiting times (minute) resource efficiency (%) triage fast track ed physician hospitalization triage fast track ed physician hospitalization triage fast track ed physician hospitalization 1 2 2 2 14 122.92 4634 446 55 0.74 0.98 0.84 0.9 2 4 2 2 14 10.56 4780 458 56 0.68 0.98 0.84 0.9 3 2 2 4 14 126.48 4842 4.8 61.6 0.74 0.98 0.79 0.9 4 2 2 2 14 124.74 4899 467 65 0.74 0.99 0.85 0.89 5 2 2 4 14 134.13 5217 4.99 80.1 0.74 0.98 0.79 0.9 6 2 2 2 14 123.82 4998 463 76 0.74 0.98 0.84 0.9 7 2 2 2 14 143.7 5513 461 69 0.74 0.98 0.84 0.9 8 2 2 1 14 397.41 12743 12026 0.03 0.68 0.92 1 0.99 9 2 2 2 14 130.29 4943 462 63 0.74 0.98 0.84 0.9 10 4 2 2 14 18.46 5143 459 70 0.68 0.98 0.84 0.9 11 2 4 2 14 115 4 662 63.25 0.74 0.88 0.83 0.92 12 2 2 2 14 122.54 4618 459 64 0.74 0.98 0.84 0.9 13 1 2 2 14 3389 37 212.5 9.39 0.99 0.98 0.78 0.96 14 2 1 2 14 6836 44381 42 0 0.02 1 0.57 0.99 15 2 2 2 14 136.78 5053 447 60 0.74 0.98 0.84 0.9 16 2 1 2 14 6831 44380 43.3 0 0.02 1 0.57 0.99 17 2 2 2 14 123.18 4622 457 64 0.74 0.98 0.84 0.9 18 2 2 2 14 134.45 4795 468 48 0.74 0.98 0.84 0.9 19 4 2 2 14 12.34 4777 450 49 0.68 0.98 0.84 0.91 20 2 2 2 14 127.23 4814 457 79 0.74 0.98 0.84 0.9 21 1 2 2 14 3407 37 208.8 11.73 1 0.98 0.78 0.96 22 2 2 2 14 136.48 5053 447 60 0.74 0.98 0.84 0.9 23 2 2 2 14 140.7 5513 461 67 0.74 0.98 0.84 0.9 24 2 2 0.5 14 461.76 13825 12023 0.2 0.67 0.92 1 0.99 25 2 2 2 14 122.58 4638 451 56 0.74 0.98 0.84 0.89 26 2 2 2 14 124.3 4814 462 67 0.74 0.98 0.85 0.9 27 2 2 2 14 136.78 4943 446 60 0.74 0.98 0.84 0.9 28 2 2 2 14 128.6 4634 451 53 0.74 0.98 0.84 0.9 29 2 1 2 14 6830 44360 42.3 0 0.02 1 0.57 0.99 30 2 2 0.5 14 481.64 14060 12063 0.14 0.67 0.92 1 0.99 31 2 2 2 14 123.82 5513 462 60 0.74 0.99 0.84 0.9 32 2 2 2 14 130.29 5425 461 76 0.74 0.98 0.84 0.9 33 2 4 2 14 114 3.9 689 58.9 0.74 0.88 0.83 0.92 34 2 2 2 14 123.2 4899 463 65 0.74 0.98 0.84 0.9 35 1 2 2 14 3385 37.29 208 8 0.99 0.98 0.78 0.97 36 2 2 2 14 128.6 4888 448 63 0.74 0.98 0.84 0.9 37 2 2 2 14 134.45 5017 450 63 0.74 0.98 0.84 0.9 38 2 4 2 14 114 3.95 691 59.4 0.74 0.88 0.83 0.92 39 2 2 4 14 121.29 4711 4.54 84.1 0.74 0.98 0.79 0.89 table 4: the results of optimization study of 4 studied factors or resources in the emergency department (ed) item triage fast track ed physician hospitalization patients’ waiting time optimum 3.22 158.97 458.21 57.03 real (before experiment) 139.72 5158.57 458.21 57.03 units’ efficiency coefficient (%) optimum 0.69 0.84 0.84 0.9 real 0.74 0.98 0.84 0.9 times are presented as minute. comprehensively integrated in the hospital information system (his), for ensuring reliability and completing the data, the researcher simultaneously used two ways: attending the emergency department and his data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e44 6. conclusion using the studied optimization method creates a significant improvement in patient waiting time and the optimization of patient stream in the ed is possible through appropriate allocation of the human and material resources. it is suggested to study the optimization of patient stream through machine learning methodology for improving the other sections of hospital departments. 7. declarations 7.1. acknowledgments we would like to thank the “clinical research development center of baqiyatallah hospital” for their kind cooperation. 7.2. authors’ contributions concept and design: km, my, smhs. acquisition, analysis, or interpretation of data: km & ma. drafting of the manuscript: km & my. critical revision of the manuscript:smhs & my. administrative, technical, or material support:my, smhs. supervision: my & smhs. all authors read and approved the final version. 7.3. funding and supports none. 7.4. competing interests the authors declare that they have no competing interests. 7.5. ethics approval and consent to participate the medical research ethics committee of iran reviewed the study protocol and concluded that the research is not subject to the iran medical research involving human subjects act, and therefore, ethics approval was waived. the necessity for obtaining informed consent was waived by the medical research ethics committee of iran, due to the complete anonymity of the study data. therefore, study data was in no way traceable to individuals. 7.6. consent for publication not applicable. 7.7. availability of data and materials original data remain available and access may be provided upon reasonable request. 7.8. availability of data and materials original data remain available and access may be provided upon reasonable request. references 1. azadeh a, pourebrahim ahvazi m, motevali haghighii s, keramati a. simulation optimization of an emergency department by modeling human errors. simul modeel pract th. 2016;67:117-36. 2. van hoof sj, quanjel tc, kroese me, spreeuwenberg md, ruwaard d. substitution of outpatient hospital care with specialist care in the primary care setting: a systematic review on quality of care, health and costs. plos one. 2019;14(8):e0219957. 3. brailsford s, vissers j. or in healthcare: a european perspective. eur j oper res. 2011;212(2):223-34. 4. waring jj, bishop s. lean healthcare: rhetoric, ritual, and resistance. soc sci me. 2010;71(7):1332-40. 5. meskarpour-amiri m, shams l, nasiri t. identifying and categorizing the dimensions of iran’s health system response to the covid-19 pandemic. j. mil. med. 2020;22(2):108-14. 6. dufour i, chouinard m-c, dubuc n, beaudin j, lafontaine s, hudon c. factors associated with frequent use of emergency department services in a geriatric population: a systematic review. bmc geriatr. 2019;19(1):185. 7. amiri mm, 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knowl. based syst. 2010;23(8):890-900. 16. azadeh a, hosseinabadi farahani m, torabzadeh s, baghersad m. scheduling prioritized patients in emergency department laboratories. comput. methods programs biomed. 2014; 117(2):61-70. 17. granja c, almada-lobo b, janela f, seabra j, mendes a. an optimization based on simulation approach to the patient admission scheduling problem using a linear programing algorithm. j. biomed. inform. 2014; 52: 42737. 18. roberts sd, editor. tutorial on the simulation of healthcare systems. proceedings of the 2011 winter simulation conference (wsc); 2011 dec 11-14; phoenix, az, usa. new jersey: institute of electrical and electronics engineers, inc.; 2011: 1403-14. 19. gunal mm, pidd m, editors. understanding accident and emergency department performance using simulation. proceedings of the 2006 winter simulation conference(wsc); 2006 dec 3-6; monterey, ca, usa. new jersey: institute of electrical and electronics engineers, inc.; 2006: 446-52. 20. zeng z, ma x, hu y, li j, bryant d. a simulation study to improve quality of care in the emergency department of a community hospital. j. emerg. nurs. 2012; 38(4): 322-8. 21. norouzzadeh s, garber j, longacre m, akbar s, riebling n, clark r. a modular simulation study to improve patient flow to inpatient units in the emergency department. j. hosp. adm. 2014;3(6):205-15. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e71 or i g i n a l re s e a rc h usability of emergency department information system based on users’ viewpoint; a cross-sectional study sohrab almasi1, nahid mehrabi1∗, farkhondeh asadi2, mahboobeh afzali3 1. department of health information technology, school of paramedical sciences, aja university of medical sciences, tehran, iran. 2. department of health information technology and management, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, school of paramedical sciences, aja university of medical sciences, tehran, iran. received: june 2022; accepted: july 2022; published online: 1 september 2022 abstract: introduction: the emergency department is of special importance due to its emergency and vital services, the high volume of referrals, and the patients’ physical condition. thus, it requires a well-designed information system with no usability problems. this study aimed to evaluate the usability of the emergency department information system from users’ perspectives. methods: this was a cross-sectional study. the research setting was the emergency department of 3 hospitals. the research instrument was a 37-item questionnaire adapted from the use and iso metrics questionnaires, consisting of five dimensions measuring the usefulness of the system, ease of use, ease of learning, user satisfaction, and suitability for the task. the content validity of the questionnaire was examined using the content validity ratio and content validity index, and its reliability was assessed using cronbach’s alpha (α = 0.88). results: fifty questionnaires were administered in the three hospitals, and the response rate was 80%. according to the findings, 55% of the respondents were female. the highest mean scores belonged to usefulness in emergency department information system (edis) a, ease of use in edis b, ease of learning in edis a, user satisfaction in edis c, and suitability for the task in edis a. according to the usability evaluation criteria, ease of learning (3.66 ± 0.74), usefulness (3.53 ± 0.87), and suitability for the task (3.47 ± 0.96) received the highest scores, and the lowest scores belonged to user satisfaction (3.29 ± 1.01) and ease of use (3.12 ± 1.00). conclusion: in terms of usability criteria, the emergency department information system is at a relatively good level. the usability of these systems can be further enhanced by considering the users’ working needs, improving software flexibility, customizing the software, using data visualization tools, observing consistency of features and standards, and increasing the quality of information and system services. keywords: informtation systems; hospital information systems; emergency service, hospital cite this article as: almasi s, mehrabi n, asadi f, afzali m. usability of emergency department information system based on users’ viewpoint; a cross-sectional study. arch acad emerg med. 2022; 10(1): e71. https://doi.org/10.22037/aaem.v10i1.1635. 1. introduction the emergency department is characterized by several major features, including unpredictable admission, patients’ physical condition, and time constraints to perform diagnostictherapeutic processes (1-4). these challenges, in turn, result in irrecoverable consequences such as increasing patient mortality, heavy costs, increasing waiting time and patient dissatisfaction, increasing medical errors and the incidence ∗corresponding author: nahid mehrabi; department of health information technology, aja university of medical sciences, tehran, iran. phone number: (+98) 21 43822453, fax: (+98) 21 8802 8364, email: n.mehrabi@ajaums.ac.ir, orcid: https://orcid.org/0000-0003-2840-056x. of violence, and disrupting medical services(5-7). therefore, compared with other departments, the emergency department requires considerable flexibility and instant planning of resources(8). persistent collection, and correct and timely processing of data may improve emergency department management (9). emergency department information system (edis), a component of the hospital information system, plays a key role in information management and care, as well as management processes of the emergency department (10-12). the edis enjoys numerous advantages such as improving emergency department performance (13), providing easier and faster access to patient information (14), recording much better and more accurate clinical and managerial informathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 2 tion, assisting in decision-making (14), and eliminating the limitations of paper systems such as multiple users’ simultaneous access to information and information illegibility (15). despite its increasing use in recent years in different countries (16), the edis is still not widely adopted and applied (1719). in some studies, poor display, a lack of workflow support, reduced efficiency of the emergency department, and congestion have been reported as the main disadvantages (20, 21). given the vital importance of the emergency department’s activities, the emergency department’s information systems must be free of usability problems to prevent errors. in doing so, systems and applications must be designed and used appropriately in accordance with scientific principles (22). one method to ensure the proper design of applications and health information systems is evaluating their usability. usability deals with various features of the software, including ease of learning, efficiency, ease of use, memorization, error prevention, and user satisfaction. evaluation also plays a pivotal role in software development (23, 24). according to various studies, it is necessary to observe usability principles in designing the user interface of the edis (25, 26). the usability index evaluates the performance of a product in terms of user satisfaction and increased productivity (27-30). a common method of evaluating the applicability of information systems is using the standard 9241/10 iso metric questionnaire and the use questionnaire, with approved validity and reliability (30, 31). several studies have been conducted on the evaluation of hospital information systems’ subsystems in military hospitals. based on results, the same maturity was observed in military and civilian hospitals, i.e., the third stage of the emram model. meanwhile, the potential benefits of these systems were not yet fully exploited in hospitals (32, 33). the present study aimed to evaluate ediss from the perspective of users in five dimensions of usefulness of the system, ease of use, ease of learning, user satisfaction, and suitability for the task. 2. methods 2.1. study design and setting this was a cross-sectional study conducted in 2021 in three hospitals affiliated with aja university of medical sciences, tehran, iran, which employed an edis. the questionnaires were distributed from 6 to 15 november 2021. the data were collected five days later, from 20 to 27 november. the research setting was the emergency departments of hospitals affiliated with aja university of medical sciences. multi-stage sampling was carried out. the goal was to include the emergency department of hospitals with 100 or more active beds, which led to the selection of the three hospitals. the emergency department system in two hospitals had been designed by two software companies, and in the third hospital, it had been developed by the hospital. the population comprised of users of ediss (emergency department nurses and secretaries). a sample of 50 was selected from the mentioned centers through convenience sampling. to maintain confidentiality, the identities of vendors and hospitals remained anonymous and they were labeled as edis a, edis b, and edis c. this study was approved by the ethics committee of aja university of medical sciences, iran (ir.ajaums.rec.1400.215). 2.2. participants the inclusion criteria were as follows: having > five years of work experience and 1 year of experience with the edis. fifty emergency information system users met the aforementioned criteria in the three hospitals. 2.3. data collection to evaluate the usability of edis, the standard 9241 iso metric questionnaire (part 10) and the use questionnaire were administered (appendix 1). the 9241 iso metric questionnaire consists of 75 questions based on seven principles: suitability for tasks, self-description, controllability, error tolerance, suitability for personalization (customization), and suitability for learning (34). the validity and reliability of the 9241 iso metric questionnaires have been confirmed in various studies (30, 31). the use questionnaire includes 30 questions that assess the following dimensions: usefulness, satisfaction, ease of use, and ease of learning (31). the validity and reliability of the use questionnaire have also been confirmed in a number of studies (35, 36). the questionnaire administered in this study was a combination of the two mentioned questionnaires, which covered five dimensions of system usefulness, ease of use, ease of learning, user satisfaction, and suitability for the task. the questionnaire encompassed a total of 37 questions on a five-point likert scale ranging from completely disagree (score: 1) to completely agree (score: 5). the number of questions for each dimension was as follows: usefulness of the system (eight questions), ease of use (10 questions), ease of learning (six questions), user satisfaction (seven questions), and suitability for the task (six questions). experts determined the content validity of the questionnaire using the content validity ratio (cvr) and content validity index (cvi), and its reliability was assessed using cronbach’s alpha (α = 0.88). then, the questionnaire was administered to 50 system users. 2.4. statistical analysis we employed the spss 22 software (ibm spss, armonk, ny, usa) for data analysis. descriptive tests (mean, percentage, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e71 table 1: baseline characteristics of the respondents variable number (%) gender male 18 (45.0) female 22 (55.0) education level high-school diploma 3 (7.50) associate degree 2 (5.00) bachelor’s degree 28 (70.00) master’s degree 5 (15.00) doctoral degree 1 (2.50) occupation nursing supervisor 3 (7.50) nurse 26 (65.00) secretary 11 (27.50) and frequency) were used to assess the data. for data analysis, the means and standard deviations (sd) were calculated, and then, the systems were compared against usability criteria. the relationship between the dimensions of usability and participants’ variables was assessed using pearson correlation coefficient or spearman correlation coefficient. 3. results 3.1. baseline characteristics of participants fifty questionnaires were administered in the three hospitals (response rate = 80%). the baseline characteristics of the respondents are given in table 1. 55% of the respondents were female and 70% had a bachelor’s degree. the mean age of the respondents was 29.8 ± 8.7 years. also, their mean work experience and mean duration of involvement with the edis was 8 ± 5.1 and 7.1 ± 4.3 years, respectively. 3.2. usefulness the highest mean scores for this criterion were reported for edis a (3.59 ± 0.78), edis b (3.54 ± 1.12), and edis c (3.48 ± 0.73), respectively. in edis a, the highest score belonged to the item "edis saves time (3.92 ± 0.49)", and the lowest score belonged to “edis meets your needs (3.3 ± 0.94)". as for edis c, the highest score was associated with "edis is useful and valuable (4 ± 0.42)", and the lowest score was related to "edis meets your needs (2.83 ± 0.93)" (table 2). 3.3. ease of use the highest mean scores for this criterion belonged to edis b (3.13 ± 1.07) and edis c (3.13 ± 0.90), respectively, while the lowest scores were reported for edis a (3.10 ± 1.05). in edis b, the highest score belonged to "using the edis does not necessarily require much effort (3.53 ± 1.06)", whereas the lowest score pertained to “using the edis, i can quickly and easily recover errors (2.8 ± 1.26)". as for edis c, the highest score was associated with "edis is user-friendly (3.66 ± 0.65)" and the lowest score was related to "using the edis, i can quickly and easily recover the errors (2.83 ± 0.83)" and "edis is flexible (2.83 ± 0.83)". with regard to edis a, the highest score belonged to "using the edis is easy and simple (uncomplicated) (3.23 ± 0.83)" and the lowest score pertained to "i noticed no inconsistencies when using the edis (2.76 ± 1.02)". 3.4. ease of learning for this criterion, the highest mean scores were obtained by edis a (3.77 ± 0.73), edis c (3.67 ± 0.70), and edis b (3.54 ± 0.81), respectively. in edis a, the highest score was related to "i will learn to work with the software quickly (4.00 ± 0.49)" and "if i do not use the emergency information system for a long time, i will most likely re-learn and re-use it easily (4.00 ±0.57)". as for edis b, the highest score belonged to "i quickly learn the required skills to use the edis (4.00 ± 0.53)" and "i quickly learn to work with software (4.00 ± 0.53)", whereas the lowest score pertained to "in order to use the edis correctly, you have to remember a lot of details (2.60 ± 1.05)". regarding edis c, the highest score was associated with "i learn to work with software quickly (4.25 ± 0.45)" and the lowest score was related to "learning the principles and instructions of working with software is easy (3.25 ± 0.75)". 3.5. user satisfaction for this criterion, the highest mean scores were obtained for edis c (3.33 ± 0.97), edis a (3.30 ± 1.08), and edis b (3.26 ± 0.98), respectively. in edis c, the highest score was related to "i feel that such a system is needed (3.66 ± 0.77)" and the lowest score was associated with "the edis works as expected (2.91 ± 0.90)". regarding edis a, the highest score was related to "i feel that such a system is needed (3.69 ± 1.01)" and the lowest score pertained to "using the emergency information system is fun (3 ± 1.15)". in the case of edis b, the highest score was allocated to "i feel such a system is needed (3.77 ± 0.77)" while the lowest score was reported for "the emergency information system is excellent (2.8 ± 1.08)". 3.6. suitability for the task for this criterion, the highest mean scores were obtained for edis a (3.53 ± 0.94), edis c (3.49 ± 0.95), and edis b (3.41 ± 1.03), respectively. in edis a, the highest score belonged to "software outputs (reports) are suitable for user tasks (3.92 ± 0.95)" and the lowest score was related to "screen fields are fitted to user tasks (3.15 ± 0.89)". as for edis c, the highest score was related to "the information required by the user is available on the screens (3.66 ± 0.88)" while the lowest score this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 4 table 2: mean score of emergency department information systems (edis) usability criteria in three hospitals (a, b, and c) systems usability criteria usefulness ease of use ease of learning user satisfaction suitability for the task edis a 3.59±0.78 3.10±1.05 3.77±0.73 3.53±0.94 3.30±1.08 edis b 3.54±1.12 3.13±1.07 3.54±0.81 3.26±0.98 3.41±1.01 edis c 3.48±0.73 3.13±0.90 3.67±0.70 3.33±0.97 3.49±0.95 total 3.53±0.87 3.12±1.01 3.66±0.74 3.29±1.01 3.47±0.96 data are presented as mean ± standard deviation. table 3: relationship between the usability criteria of the emergency department information system (edis) and baseline characteristics of participants variable usefulness ease of use ease of learning user satisfactionr suitability for task education level cc 0.01 -0.03 0.03 -0.04 -0.02 p-value 0.92 0.81 0.84 0.79 0.90 occupation cc 0.12 0.14 0.27 0.21 0.16 p-value 0.42 0.36 0.08 0.18 0.32 age cc -0.20 -0.37 -0.20 -0.36 -0.23 p-value 0.19 0.01 0.20 0.02 0.14 work experience cc -0.32 -0.28 -0.30 -0.34 -0.33 p-value 0.03 0.07 0.05 0.02 0.03 experience with edis cc -0.24 -0.34 -0.12 -0.24 -0.21 p-value 0.12 0.03 0.43 0.12 0.17 cc: correlation coefficient. was related "edis provides support for users’ daily activities (3.16 ± 1.02)". as for edis b, the highest score pertained to "edis provides support for users’ daily activities (3.66 ± 0.81)" and the lowest score pertained to "it is possible to adjust the display of results (information) to the user’s needs (3.26 ± 1.16)". 3.7. relationship between usability criteria and participants’ characteristics with increase in the level of education, age, work experience, or experience of working with the system, user satisfaction with each dimension of system usability declined. evidence also shows that there is a stronger correlation between job and satisfaction with usability than between other variables (table 3). 4. discussion based on the findings of this study, the ease of use criterion received the lowest score among the criteria. consistency in the displayed information and quick recovery of errors received the lowest scores as the sub-criteria of ease of use. in the study by khajouei et al. (37), the most important recommendations for creating consistency and standards were: arranging numbers, fields, menu items, and the cursor equally and according to the standard on all pages; having an active exit button on each window; and using the same icon for buttons having the same function. as for the feature of helping users identify and correct errors, the most important recommendations were: presenting all the messages in one language (persian) with accurate and consistent grammar, without using exclamation marks, and in positive statements. indicating the severity of the error, the cause of the problem, and the necessary activities to recover the error are also recommended. in case of an error related to several data entry fields, after viewing and confirming it, the user should be directed to the relevant fields. moreover, the software meeting the expectations and users enjoying working with the software had the lowest score in the user satisfaction criterion. in the study by kalankesh et al., factors such as the quality of the information provided by the system, system quality, quality of services provided by the system, quality of vendor company support for the software and its users, and the compatibility of system performance with expectations were deemed useful for improving users’ satisfaction with the information systems (38). various studies show that paying attention to the design of the system’s this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e71 user interface (in terms of allowing the background color, fit, order, and sequence of icons, and menus to be adjusted with the work processes of the emergency department), the use of data visualization tools, software speed, personalization, and system font size may increase user satisfaction with the edis (39, 40). in an applied research on the usability of hospital information systems, sadoughi et al. concluded that user satisfaction, perceived usefulness, meeting the expectations, and the intention to continue using the system were indicators of the success or failure of the system; thus, it is essential to resolve the deficiencies that reduce satisfaction with the system (41). findings related to the suitability for the task criterion showed that the studied systems have a relatively optimal score in this dimension(3). among the strengths of the systems examined in the emergency departments were the suitability of software outputs (reports) for the user’s tasks, and the existence of information required by the user on the screen. still, these systems scored poorly in terms of the fit of the screen fields and the possibility of personalizing the screen for user tasks. in the study by farley et al., the poor user interface design was reported as a limitation of the edis, which caused difficulties for users in accessing the required information(12). in the study by callen et al., despite improving coordination and communication between providers, the use of this system had limitations in terms of quick access to patient information, increasing information registration time, and user-friendliness, which necessitated the use of innovative methods for collecting and displaying emergency department information (42). agharezaei et al. also found that from the users’ point of view, the systems are simple, working with these systems is not particularly complicated, and they are easy to learn, but they lack flexibility. it is thus suggested to pay more attention to this component when designing the system (43). findings related to the usefulness criterion indicated that the systems under review received good scores regarding increasing efficiency and productivity, facilitating activities, and better control and management of tasks. the results related to this criterion are in line with the findings of other studies examining ways to increase system usefulness (44, 45). furthermore, the ease of learning criterion had the highest score compared to the other criteria. the results of this study showed that features such as few learning details when working with the system and the small number of learning instructions were positive features of the systems under study. the literature shows that educating users about using the system and paying attention to the design of these systems to allow users to easily navigate the systems and learn them with little effort promote the learning of the system (4648). therefore, observing the principles of usability in health information systems can promote efficiency and user satisfaction, reduce errors, and ultimately improve patient safety and quality of care (49). this is even more critical in systems used in departments such as the emergency department, where due to the critically ill status of patients, as well as numerous and unpredictable referrals, the users’ focus is diminished and they need easy-to-use systems (50, 51). 5. limitations to evaluate the usability of edis, we administered a researcher-made questionnaire based on the standard 9241 iso metric questionnaire part 10 and the use questionnaire. the questionnaires had previously been used in other studies assessing the usability of hospital information systems (28, 52). however, in this study, only the quantitative method was adopted to evaluate the usability of the edis. a mixed-methods study (quantitative and qualitative) is recommended to gain better insight into the usability problems of the ediss. other limitations of this study include the lack of cooperation of some system users and users’ unfamiliarity with this system. due to the existence of different processes and structures in the emergency departments, the results of this study may not be generalizable to other settings. still, out of the three examined information systems, two had been developed by different companies, and one had been designed within the hospital, and this diversity may improve generalizability. to promote the usability of these systems, the following recommendations are made: understanding the needs of users and the work environment, identifying the type of users and their diverse needs in a versatile environment, paying attention to work processes and seemingly unimportant issues, designing the interface according to common principles and models, involving end-users in information system design, conducting usability tests, and applying final edits before implementing the system. 6. conclusion the results of this study show that the studied emergency systems are at a desirable level in terms of usability. nevertheless, considering the following factors in designing these systems might increase the usability of edis: foreseeing users’ work needs, greater software flexibility, consistency of features and standards, similarity across the system, customizing users’ screens according to their needs, incorporating data visualization tools, quality of the information provided by the system, system quality, quality of after-sales services, software maintenance support, and displaying information such that users can easily understand them. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 6 7. declarations 7.1. acknowledgments we would like to express our sincere gratitude towards the personnel of the emergency departments of hospitals affiliated with aja university of medical sciences. 7.2. authors’ contributions s. almasi, n. mehrabi, f. asadi and m. afzali: concept and design. s. almasi: literature search. s. almasi: collecting the data. s. almasi and n. mehrabi: data analysis and interpretation. s. almasi: manuscript drafting. n. mehrabi, and f. asadi and m. afzali: editing and critical review. all authors wrote and reviewed the manuscript. 7.3. funding and supports this study was financially supported by aja university of medical sciences. 7.4. competing interests the authors declare that they have no competing interests. 7.5. availability of data and materials the datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. references 1. steptoe ap, corel b, sullivan af, camargo ca. characterizing emergency departments to improve understanding of emergency care systems. international journal of emergency medicine. 2011;4(1):42. 2. khademian z, sharif f, tabei sz, bolandparvaz s, abbaszadeh a, abbasi hr. teamwork improvement in emergency trauma departments. iranian journal of nursing and midwifery research. 2013;18(4):333-9. 3. redley b, botti m, wood b, bucknall t. interprofessional communication supporting clinical handover in emergency departments: an observation study. australasian 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10(1): e71 appendix 1: study questionnaire the present questionnaire is to evaluate the usability of the emergency department information system (edis) in critical situations at educational and medical centers affiliated to the aja university of medical sciences from the users’ viewpoints with a focus on five dimensions: usefulness, ease of use, ease of learning, user satisfaction and suitability for the task. the questionnaire includes phrases with the abovementioned dimensions, please give your valuable opinion on each phrase by marking the available scales. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e15 or i g i n a l re s e a rc h clinical features and outcomes of acute chlorine gas inhalation; a brief report taymmia ejaz1∗, sheema saadia1, safia akhlaq1, adil aziz1, muhammad arslan ahmed1, aisha fareed siddiqui1 1. department of medicine, the aga khan university hospital, karachi, pakistan. received: january 2022; accepted: january 2022; published online: 14 february 2022 abstract: introduction: on march 6th,2020, chlorine gas leak was reported at engro polymer & chemicals plant in karachi city, pakistan. this study aimed to evaluate the clinical features and outcomes of patients who presented to emergency department (ed) following this event. methods: this retrospective cross-sectional study, evaluated the clinical features and outcomes (length of hospital stay, complications, and mechanical ventilation requirement) of patients presenting to ed of aga khan university hospital, karachi, pakistan, with history of chlorine gas exposure at the engro plant from 6th march to 14th march 2020. results: 38 patients with mean age of 33.1 ± 8.1 years presented to ed with history of chlorine gas exposure (100% male). 4 (10.5%) cases had comorbid diseases. most common presenting symptom was dyspnea, observed in 33 (86.8%) cases, followed by cough, seen in 27 (71.1%) subjects. 13.2% (5/38) patients had infiltration on chest x-ray and 33 (86.8 %) required hospitalization. 6 (15.8%) patients had repeat presentation requiring hospitalization or ed visit. 18 (47.4%) were managed with high flow oxygen therapy, 9 (23.7%) required non-invasive ventilation and one patient was intubated due to development of pneumo-mediastinum. mean length of stay was 1.55 ± 1.58 days and no patients died. presence of tachycardia was the only finding significantly associated with need for oxygen (p = 0.033) and non-invasive ventilation (p = 0.012). conclusion: the majority of patients presenting with acute chlorine gas exposure showed good clinical outcomes and rapid recovery, however, a high index of suspicion and vigilance should be maintained for complications such as pneumomediastinum and acute respiratory distress syndrome in these patients. keywords: inhalation exposure; poisoning; accidents, occupational; chlorine; gas poisoning; outcome assessment, health care cite this article as: ejaz t, saadia s, akhlaq s, aziz a, ahmed ma, siddiqui af. clinical features and outcomes of acute chlorine gas inhalation; a brief report. arch acad emerg med. 2022; 10(1): e15. https://doi.org/10.22037/aaem.v10i1.1448. 1. introduction chlorine gas, a simple halogen irritant, is available worldwide as a household and industrial chemical. through oxidation and free radical formation (1) halogen pulmonary irritants (hpis) cause respiratory mucosal damages, and concomitant ophthalmological and dermatological manifestations(2). manifestations are dose-dependent, with mucosal membrane irritation occurring at concentrations less than 15 ppm, milder respiratory clinical features at concentrations more than 30 ppm, and pneumonitis and pulmonary edema ∗corresponding author: taymmia ejaz; department of medicine, the aga khan university hospital, stadium road, karachi, 78600, pakistan. email: taymmia.ejaz@gmail.com/ taymmia.ejaz@aku.edu, tel: +923225830686, orcid: http://orcid.org/0000-0001-8748-8763. at concentrations greater than 50 ppm. death results within few to 30 minutes in exposures with 400 ppm and over 1000 ppm concentrations, respectively(2). exposure can result from multiple sources, which include industrial accidents, inappropriate use of household cleaning agents, swimming pool chlorination accidents, burning of solid chlorine products, and deliberate release as a chemical weapon such as in world war one and syrian conflict(3). health effects of chlorine gas inhalation vary based on age, comorbid conditions, exposure duration, and various other factors(3, 4). inhalational injury results in acute short-term clinical features and long-term changes in lung function, which manifest as reactive airway dysfunction(5, 6). industrial accidents resulting in large scale chlorine exposure incidents have occurred both in the developed and developing world(7-12). on march 6th, 2020, chlorine gas leak was reported at engro polymer & chemicals plant in karachi city, pakistan(13). over one hunthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. ejaz et al. 2 dred workers were reported to have been exposed and were taken to different health care facilities in karachi; some were brought to aga khan university hospital for further management. this study aimed to evaluate clinical features and outcomes of patients who were accidentally exposed to chlorine gas in the industrial accident. 2. methods 2.1. study design and setting this study is a retrospective cross-sectional study conducted in aga khan university hospital, karachi, pakistan, from march april 2020. ethical approval was taken from institutional ethics review committee aga khan university hospital (erc:2020-4918-10961). 2.2. participants all patients with history of chlorine gas exposure at the engro plant from 6th march to 14th march 2020 presenting to emergency department and those hospitalized in aga khan university hospital, karachi, pakistan were included in the study. patients were enrolled based on consecutive non-probability sampling. patients with incomplete records were excluded. diagnosis of chlorine poisoning was made based on exposure history, clinical presentation, and laboratory and radiological findings. 2.3. data collection data collection was done using a pre-designed proforma. data was collected on demographic profile, co-morbid conditions, presenting clinical features and other symptoms, examination findings, oxygen requirement, laboratory finding, imaging findings, and management. retrospective review of files and electronic health records was done. patients who had not undergone chest x-rays or arterial blood gas tests were categorized in missing data. length of hospital stay, complications, and mechanical ventilation requirement were considered as outcomes. 2.4. statistical analysis data analysis was done in spss version 23. categorical data were reported with frequencies and percentages. continuous data were reported as mean and standard deviation. normality tests were done to assess normality and parametric or nonparametric tests were used accordingly. fischer’s exact and chi-square tests were done to compare categorical data, and student t-test was done to compare quantitative data. a p-value < 0.05 was considered significant. table 1: clinical and laboratory findings of studied cases variables values symptoms dyspnea 33 (86.8) cough 27 (71.0) cough and dyspnea 25 (65.7) chest pain 17 (44.7) headache 5 (13.2) sore throat 4 (10.5) nausea 4 (10.5) vomiting 2 (5.3) physical examination tachycardia 19 (50.0) tachypnea 29 (76.3) expiratory wheeze 4 (10.5) bilateral lung crepitation 7 (18.4) arterial blood gas (n = 13) mean ph 7.35 ± 0.14 median po2 mmhg (iqr) 64 (55.5 – 94.0) median pco2 mmhg (iqr) 41.5 (38.9 46.75) laboratory parameters (n=32) hemoglobin(g/dl) 14.65± 0.99 white cell count(x109 ) 13.89± 4.64 neutrophils (%) 79.43 ±12.01 neutrophilia 17 (44.7) lactate(n=13) 2.18± 1.27 sodium(mmol/l) 139.28 ± 2.27 potassium(mmol/l) 4.00 ± 0.38 bicarbonate(mmol/l) 25.15 ± 2.74 chloride(mmol/l) 104.56 ± 1.74 troponin(ng/ml) 0.0072 ± 0.0036 data are presented as mean ± standard deviation or frequency (%). complete baseline laboratory data were available for 32 patients who were shifted to emergency room long stay area; whereas this was missing in other patients as they were observed clinically and discharged from short stay area. 3. results 38 patients with the mean age of 33.1 ± 8.1 (range: 21 55) years presented to emergency department with history of chlorine gas exposure during the defined study period (100% male). 4 (10.5%) patients had comorbid conditions (3 hypertensions, 2 diabetes mellitus, and 1 ischemic heart disease). table 1 summarizes the clinical and laboratory findings of studied cases. most common presenting symptom was dyspnea, observed in 33 (86.8%) cases, followed by cough, seen in 27 (71.1%). among the unusual presenting features, presyncope/syncope was reported by three patients and loose stools were reported by one patient. chest x-rays were done in 32 (84.2%) patients; among these patients 5/32 patients (15.6%) had abnormalities (pulmonary edema in 2 patients, pneumomediastinum and subcutaneous emphysema in one patient, bilateral inhomogeneous consolidations in one patient and infiltrates in right this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e15 table 2: management and outcomes of studied patients variables values length of stay (days) mean ± sd 1.55 ± 1.58 ≤ 1* 29 (76.3) 2 6 (15.8) ≥ 4 3 (7.9) disposition ward 24 (63.2) emergency department 7 (18.4) special care unit 6 (15.8) intensive care unit 1 (2.6) management salbutamol nebulization 32 (84.2) ipratropium nebulization 34 (89.5) systemic steroids 13 (34.2) sodium bicarbonate nebulization 2 (5.3) beclomethasone nebulization 5 (13.2) supplemental oxygen 18 (47.4) non-invasive ventilation 9 (23.7) mechanical ventilation 1 (2.6) data are presented as mean ± standard deviation (sd) or frequency (%). *: 10 (26.3%) were hospitalized for < 6 hours. infra-hilar region in one patient). table 2 shows the management and outcomes of the cases. 33(86%) patients required hospitalization and 6 (15.8%) patients had repeat presentations requiring hospitalization or emergency department visit. 18 (47.4%) were managed with high flow oxygen therapy, 9 (23.7%) required non-invasive ventilation, and one patient was intubated due to development of pneumomediastinum on repeat presentation to emergency department. mean length of stay was 1.55 ± 1.58 days and no patients died. tachycardia was the only finding significantly associated with need for oxygen supplement (p = 0.033) and non-invasive ventilation (niv ) requirement (p = 0.012; table 3). 4. discussion this study describes the presenting features, outcomes, management, and complications observed in patients after an industrial disaster resulting in accidental exposure to chlorine. the proportion of presenting affected population was significantly lower than that observed in other largerscale disasters due to smaller scale and nature of the incident. however, the findings of this study can predict what challenges and patient outcomes can occur in case of any event causing exposure on a larger scale in a metropolitan city such as karachi in a lower-middle income country. although many case studies have been published on accidental chlorine exposure due to swimming pool accidents and household exposure, there are few studies on large scale industrial exposure. all patients in our study were males and adults. this accounts for the relatively better outcomes in our study since children are reported to be more severely affected by chlorine exposure(14). this was observed in various studies as children had a higher hospitalization rate and longer hospital stay(14). the presenting features and symptoms of the patients were similar to those observed in other observational studies. cough and dyspnea were the most common symptoms observed in our study. sever et al.(11) in turkey reported similar outcomes and clinical features in 39 patients presenting to emergency department after accidental chlorine gas exposure. cough and dyspnea were seen in 64.1% and 30.8% of the patients, respectively. sever et al.(11) also reported these as the most common symptoms. in a systematic review of over 37 incidents of accidental chlorine exposure in civilians (n=1566), cough and dyspnea were also the most common presenting features, observed in 29% and 22% patients, respectively(2). in contrast, kim et al. reported headache as the most common symptom observed in patients exposed(14) and eye irritation with sneezing was common in patients in a study by ammoura et al. in jordan(7). physical signs showed significant correlation with outcomes in a study by khilji et al. from oman(9). however, tachycardia was the only finding significantly associated with oxygen or niv requirement in our study. 30.8% were asymptomatic and physical examination was unremarkable in the majority (64.1%) of patients and the most common physical examination finding was tachypnea in a study on evaluation of 39 cases of chlorine exposure by sever et al. in turkey(11). however, the majority of patients had an abnormal physical examination in our study; tachypnea was the most common physical sign, found in 29 (76.3%) patients. all 71 patients (100%) had presented with respiratory complains after the train derailment incident in graniteville, california(12). on physical exam wheeze (46%) and crackles (29%) were the most common findings; tachypnea was observed in 46%(12). gülolu et al. (8)from turkey also reported 10.4% asymptomatic subjects and normal physical examination in the majority (71.6%) of patients. only one patient (2.6%) had abnormal x-ray in the study by sever et al.(11); in contrast to 15.6% patients having abnormal chest x-ray findings in our study. non-invasive ventilation was required in 9 (27.3%) patients in our study, in comparison, no patient in their study required non-invasive or invasive mechanical ventilation. chest x-rays were done in 71.7% (76/106) and x-rays were pathological in only 6 (5.7%). in contrast, 40/71 (57%) of the hospitalized patients developed abnormal findings after the graniteville train derailment incident(12), most of these x-ray changes occurred on the first day of exposure and infiltrates were frequent findings. the role of chest-x-ray in management after chlothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. ejaz et al. 4 table 3: association between some clinical features and need for oxygen supplementation and non-invasive ventilation (niv ) variable total (n) oxygen p niv p age (years) ≥ 40 6 4 (66.7) 0.33 3 (50.0) 0.13 < 40 32 15 (46.9) 6 (18.0) chest x-ray abnormality yes 5 5 (100.0) 0.049 4 (80.0) 0.013 no 27 14 (51.9) 5 (18.5) tachypnea yes 29 16 (55.2) 0.22 9 (31.0) 0.061 no 9 3 (33.3) 0 tachycardia yes 19 13 (68.4) 0.033 8 (42.1) 0.019 no 19 6 (31.6) 1 (5.3) data presented as mean ± standard deviation (sd) or number (%). wbc: white blood cell; ct: computed tomography scan; esr: erythrocyte sedimentation rate; crp: c-reactive protein; cpk: creatine phosphokinase; ldh: lactate dehydrogenase; bun: blood urea nitrogen; copd: chronic obstructive pulmonary disease. rine exposure is controversial; most recommend it in cases of pulmonary edema or acute respiratory distress syndrome (ards), however, others recommend a baseline chest x-ray in all patients with exposure to assess radiological progression(3). kim et al.(14) did not report any laboratory abnormalities among the 209 non-hospitalized patients after chlorine exposure. arterial blood gas (abg) assessments were done in only 55 (77%) cases in a study by van sickle (12). mean ph was 7.32, which was similar to7.35 reported in our study. 25 (45%) patients had respiratory acidosis in their study as compared to 30% in our study and 18 (10%) had hypoxemia in their study as compared to 69.2% of our patients in whom abgs were assessed. similarly, abg assessments were not done in 85/106 (80.2%) patients in a study by gülolu et al.(8) among those with abg assessments,results were within normal ranges in 13/21 (61.9%), 4/21 (19.04%) had hypoxia, 3/21 (14.2%) patients had hypercarbia and one patient had hypocarbia and respiratory alkalosis. in a systematic review of 36 studies(2), overall death rate in 1566 individuals was 0.6%, all of the 9 patients who had died in that systematic review belonged to the study on graniteville train derailment incident(12).there were four cases of spontaneous pneumomediastinum (0.3%)(2). our study had one case of pneumomediastinum, and no patient died. although this study did not assess lung function tests, chlorine gas exposure can result in long-term sequela due to reduction in lung function and this was reported in various studies(10, 15, 16). masoumi et al. from neighboring iran reported significant problems, which were encountered after chlorine gas leakage in dezful, iran(10). prevention of these events requires environmental regulations, chlorine safety-related guidelines implementation and pilot safety studies in industrial installations. emergency response systems in hospitals for rapid implementation during these disasters can ensure effective management. 5. limitation limitations of our study include being single-centered and retrospective study design. exact number of exposed people is not known and patients presented to various tertiary care hospitals in karachi after the incident; therefore, outcomes of those patients are not known. distance from leakage site; exposure duration, and concentration of chlorine was not documented properly. long-term follow up of patients was not done to assess for persistence of symptoms. moreover, lung functions test during admission and postadmission were not done to assess bronchial hyperactivity. our center is a large tertiary care private hospital; therefore, the results of the study cannot be generalized to other centers in the country. 6. conclusion the majority of patients presenting with acute chlorine gas exposure showed good clinical outcomes and rapid recovery; however, a high index of suspicion and vigilance should be maintained for complications such as pneumomediastinum and acute respiratory distress syndrome in these patients. prevention of these events requires environmental regulations, chlorine safety-related guidelines implementation, and pilot safety studies in industrial installations. moreover, in case of these incidents the duration of exposure, proximity, and concentration of the toxin should be documented. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e15 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions taymmia ejaz, safia akhlaq and adil aziz designed the study. taymmia ejaz and safia akhlaq participated in acquisition of data. sheema saadia and arslan ahmed analyzed the data. adil aziz and arslan ahmed reviewed results and carried out interpretation of data. taymmia ejaz and sheema saadia wrote the initial draft and others revised the manuscript critically. all authors approved final version of the manuscript to be published and are accountable for all aspects of the work. 7.3. funding and supports none. 7.4. conflict of interest authors declare that there is no conflict of interest. references 1. carlisle m, lam a, svendsen er, aggarwal s, matalon s. chlorine-induced cardiopulmonary injury. annals of the new york academy of sciences. 2016;1374:159-67. 2. govier p, coulson jm. civilian exposure to chlorine gas: a systematic review. toxicol lett. 2018;293:249-52. 3. zellner t, eyer f. choking agents and chlorine gas history, pathophysiology, clinical effects and treatment. toxicol lett. 2020;320:73-9. 4. huynh tuong a, despreaux t, loeb t, salomon j, megarbane b, descatha a. emergency management of chlorine gas exposure a systematic review. clin toxicol (phila). 2019;57(2):77-98. 5. balte pp, clark ka, mohr lc, karmaus wj, van sickle d, svendsen er. the immediate pulmonary disease pattern following exposure to high concentrations of chlorine gas. pulm med. 2013;2013:325869. 6. hoyle gw, svendsen er. persistent effects of chlorine inhalation on respiratory health. annals of the new york academy of sciences. 2016;1378:33-40. 7. ammoura am, s.aqqad a, t.hamdan ma. chlorine gas poisoning. journal of the royal medical services2004. 8. güloğlu c, kara i̇h, erten pg. acute accidental exposure to chlorine gas in the southeast of turkey: a study of 106 cases. environmental research. 2002;88:89-93. 9. khilji mf. clinical presentations and outcomes of industrial chlorine gas exposure incidence in oman. prehospital and disaster medicine. 2021;36:18-24. 10. masoumi g, maniey m, aghababaeian h, ostadtaghizadeh a, araghi ahvazi l. lessons learned from a chlorine gas leakage in dezful city, iran. disaster medicine and public health preparedness. 2020:1-7. 11. sever m, mordeniz c, sever f, dokur m. accidental chlorine gas intoxication: evaluation of 39 patients. journal of clinical medicine research. 2009. 12. van sickle d, wenck ma, belflower a, drociuk d, ferdinands j, holguin f, et al. acute health effects after exposure to chlorine gas released after a train derailment. am j emerg med. 2009;27(1):1-7. 13. bhatti mw. 137 faint in port qasim industrial gas leakage. the news. 7th march 2020. 14. kim j-a, yoon s-y, cho s-y, yu j-h, kim h-s, lim g-i, et al. acute health effects of accidental chlorine gas exposure. ann occup environ med. 2014;26. 15. christensen be, duncan ma, king sc, hunter c, ruckart p, orr mf. challenges during a chlorine gas emergency response. disaster med public health prep. 2016;10(4):553-6. 16. clark ka, karmaus wj, mohr lc, cai b, balte p, gibson jj, et al. lung function before and after a large chlorine gas release in graniteville, south carolina. ann am thorac soc. 2016;13(3):356-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 151 emergency (2014); 2 (4): 151-157 original research the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study marjan hosseini1, zohreh karami1, atousa janzadenh2, seyed behnamedin jameie3,4, zahra haji mashhadi1, mahmoud yousefifard1, farinaz nasirinezhad4* 1. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran 2. basic science department, faculty of allied medical sciences, iran university of medical sciences, tehran, iran 3. department of basic sciences, faculty of allied medicine, iran university of medical sciences, tehran, iran 4. physiology research center, department of physiology, iran university of medical sciences, tehran, iran abstract introduction: neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. muscimol as a new agonist of gamma-aminobutyric acid receptor type a (gabaa) have been introduced for pain management. thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as gabaa receptor agonist in spinal cord injury (sci) model of neuropathic pain. methods: in the present experimental study, male wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t.) three weeks after induction of spinal cord injury using compression injury model. neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. the time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. results: muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; f= 6.6; p<0.001), mechanical hyperalgesia (df: 24, 5; f= 7.8; p<0.001), cold allodynia (df: 24, 5; f= 6.96; p<0.001), and mechanical allodynia (df: 24, 5; f= 15.7; p<0.001). the effect of doses of 0.1 µg and 1 µg were also significant. in addition, the efficacy of different doses of muscimol did not have difference on thermal hyperalgesia (df: 24, 5; f= 1.52; p= 0.24), mechanical hyperalgesia (df: 24, 5; f= 0.3; p= -0.75), cold allodynia (df: 24, 5; f= 0.8; p= -0.56), and mechanical allodynia (df: 24, 5; f= 1.75; p= 0.86). conclusion: the finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. in addition, the effect of gabaa agonist is short term and its effectiveness gradually decreases by time. key words: neuropathic pain; gabaa receptor agonists; muscimol; pain management cite this article as: hosseini m, karami z, janzadeh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. emergency. 2014;2(4):151-7. introduction:1 oday neuropathic pain, which happens following the injury or dysfunction of peripheral or central nervous system, turns to one of the important medical challenging about pain. in most of these situations, neuropathic pain involve the at-level of injury but gradually extend and can occurred above or below the level of injury. these changes lead to decrease life quality, functional loss and physical dependence, and undermine mental health and social relations (1). the most annoying symptoms of these patients are hyperalgesia (hypersensitivity to painful stimulus) and allodynia (pain due to a stimulus which does not normally aggravate priorities weather in acute or in chronic cases (2). however, eliminating of these symptoms is one *corresponding author: farinaz nasirinezhad; physiology research center, department of physiology, iran university of medical sciences, shahid hemmat highway, tehran, iran. tel/fax: +982188622709. email: nasirinezhad.f@iums.ac.ir received: 3 may 2014; accepted: 8 june 2014 of the current treatment strategies have less efficiency and lead only to decrease 30-40% of pain in less than half of patients (3). medications in this situation align with some problems such as not responding to drugs and their side effects. for example, weight gain and constipation are common symptoms of patients with spinal cord injuries (sci) treated with tricyclic antidepressants (2). because of drug resistance, using narcotic drugs is not acceptable and long-term use of antiepileptic drugs, gabapentin, and topiramate has a low effectiveness (4-6). in patients with sci even narcotic drugs, which are one of the best sedative agents, have a poor or moderate responses (6). alternatively, intrathecal (i.t) pumps are one of the new common cures (7, 8). intrathecal baclofen has remarkable effects on reducing the symptoms of sci-related pain due. but applying this medication in some patients causes to worsen the neuropathic pain symptoms (9). intrathecal clonidine has also been suggested in some studies (8). t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 152 epidural and intrathecal use of sedative drugs has been widely applied and there are strong evidences for their helpfulness in acute and chronic situation. most trials and a meta-analysis have shown that preoperative, intraoperative and postoperative epidural anaesthesia /analgesia reduces the incidence of phantom pain significantly (10, 11). opioids, local anesthetics, alha2 agonists, and baclofen are the most significant drugs of this group. along with these agents, newest drug compounds like sodium channel blockers, trophic factors, and new agonist of gamma-aminobutyric acid (gaba) receptors have also been introduced (12-14). one of the type a of gaba (gabaa) receptor agonists is muscimol which is extracted as a psychotropic drug from a mushroom named amanita muscaria and used as a local anesthetic drug (15, 16). efficacy of muscimol on reducing the neuropathic pain symptoms has been shown in some studies, while in most of them the peripheral model of neuropathic pain has been used (15, 17). since the main cause of neuropathic pains is direct injury of spinal cord, evaluating the effectiveness of intrathecal pumps of muscimol in reducing the neuropathic pain arisen from sci has not yet been cleared. thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as gabaa receptor agonist in spinal cord injury (sci) model of neuropathic pain. methods: study design and setting: the present experimental study was conducted in accordance with guidelines of ethics for the evaluation of pain in conscious animals (18) and approved by the ethic committee of iran university of medical sciences, tehran, iran. the length of trials was kept short as much as possible and the number of animals taken to a minimum with all efforts made to minimize animal suffering. animals and drugs: thirty male wistar rats (10 rats in each group) weighing 140-160 g were used. animals were maintained under controlled laboratory conditions (temperature: 21 ± 1 c; 12 hour light/dark cycle; 4 rats per cage) and had free access to water and food. all tests were performed between 10:00 am and 02:00 pm, in a soundproof and air-regulated room. muscimol (sigma chemical company, st, louis, usa) was dissolved in saline and the animals received 0.01, 0.1 or 1 ug/10ul, intrathecally (i.t.). before muscimol administration and 15 minutes, one hour and three hours after on, behavioral tests were evaluated. animal preparation a compression injury model was used to induce sci. this method was previously described by hama and sagen (19). briefly, after anesthesia [by a combination of ketamine (80 mg/kg) and xylazin (10 mg/kg)], dorsal laminectomy was performed at t6–t8 to expose the spinal cord. the lower blade of the micro-vascular clip (harvard apparatus, ma) was placed on the exposed cord with avoidance of damage to the adjacent nerve roots. after 60 seconds, the clip was removed, muscles sutured shut, and skin closed. three weeks following compression, a pe10 cannula was placed intrathecally at l5-l6 level of spinal cord during deep anesthesia based on the method introduced by xu et al (20). for this purpose, a longitudinal skin incision was made over l4-l5 location and a 6 cm long pe10 cannula implanted into the subarachnoid space and passed 1 cm rostrally. behavioral tests a) mechanical allodynia the threshold of mechanical allodynia, as a behavioral measure of neuropathic pain, was measured by assessing hind paw sensitivity to innocuous mechanical stimulation to third metatarsal bone area of the both hind paw. the 50% paw withdrawal thresholds were evaluated with a set of specific von frey filaments using the up-down paradigm (21). lifting, shaking, or licking the paw and running away were considered as positive responses. the 50% paw withdrawal thresholds were assessed before and 15 minutes, 1 hour, and three hours after muscimol administration. only robust and immediate withdrawal responses including lifting, shaking or licking the paw and running away were considered as positive. b) mechanical hyperalgesia increasing mechanical pressure (48 g/s) was applied to the hind paw by the randall–selitto mechanical hyperalgesia test for the assessment of mechanical hyperalgesia. it can detect neuropathic pain in both fore paws and hind paws (22). the mechanical force was applied to the plantar surface of both hind paws (two trials per each paw) until a withdrawal response observed. the maximum applied pressure was 1000 g to evade damage. the average score of two trials was used in analysis. c) cold allodynia the application of a drop (0.1 ml) of acetone to the center of plantar surface of hind paw was performed to measure cold allodynia (23). rats were located on a mesh floor cages and acetone pushed to center of plantar surface of hind paw. this test was repeated five times per foot (3–5 min between each test) and withdrawal responses calculated as the percentage response frequency using following formula: d) heat hyperalgesia responses to noxious heat (hargreaves method) were evaluated using a radiant heat source (24). animals this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 153 emergency (2014); 2 (4): 151-157 were placed in a transparent plexiglas box and allowed to adapt within 20 minutes. time to initiating the thermal stimulation to paw withdrawal response was defined as withdrawal latency. a cut-off time was set at 25 seconds to prevent tissue damage. each hind paw was tested three times. finally, the average of three trials was used for statistical analysis. statistical analysis data were entered to spss version 20 and expressed as mean ± sem (standard error of mean). one-way analysis of variance (one-way anova) was used to compare the difference among three groups before administration of muscimol. repeated measures anova was carried out to change the pain over time among before, 15 minutes, 60 minutes, and 180 minutes after treatment to clear the time of peak effect. for assessment of dosage effect, analysis of covariance (ancoa) adjusted for mean pain score before muscimol administration was performed. because the maximum effect was observed at 15 minutes, two-way anova was performed to evaluate the significant difference among three doses of muscimol in this time. p <0.05 was defined as the significance level. results: muscimol administration causes to reduce the symptoms of neuropathic pain, noticeably. as shown in table 1, thermal hyperalgesia, mechanical hyperalgesia, cold allodynia, and mechanical allodynia decreased after 15 minutes. except thermal hyperalgesia (df: 24, 5; f=1.1; p=0.12), other neuropathic pain symptoms had significant improvement after one hour and three hours of muscimol administration. using muscimol with the dose of 0.01 µg/kg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; f= 6.6; p<0.001), mechanical hyperalgesia (df: 24, 5; f= 7.8; p<0.001), cold allodynia (df: 24, 5; f= 6.96; p<0.001), and mechanical allodynia (df: 24, 5; f= 15.7; p<0.001). muscimol with a dose of 0.1 µg/kg also led to improve the thermal hyperalgesia (df: 24, 5; f= 5.9; p<0.001), mechanical hyperalgesia (df: 24, 5; f= 7.2; p<0.001), cold allodynia (df: 24, 5; f= -7.03; p<0.001), and mechanical allodynia (df: 24, 5; f= -13.4; p<0.001) after 15 minutes of administration. the significant effect was also seen with a dose of 1 µg/kg (figure 1). the analysis of covariance showed that the efficiency of various muscimol doses was similar in reducing the symptoms of pain in different times. based on this result, the efficacy of different doses of muscimol did not have difference on thermal hyperalgesia (df: 24, 5; f= 1.52; p= 0.24), mechanical hyperalgesia (df: 24, 5; f= 0.3; p= -0.75), cold allodynia (df: 24, 5; f= 0.8; p= -0.56), and mechanical allodynia (df: 24, 5; f= 1.75; p= 0.86) (figure 2). discussion: the findings of the present study showed that using muscimol in each of three evaluated doses leads to reduce the acute neuropathic pain. peak alleviating effect, was observed within 15 minutes and gradually decreases in three hours. however, except heat hyperalgesia, intrathecal administration of muscimol could remarkably relief the other symptoms. this effect has persisted until three hours after administration. it table 1: effectiveness of muscimol prescrition on neuropatic pains in different times  type of test before administration after 15 minutes the first hour the third hour thermal hyperalgesia (second) 0.01µg 10.4 (0.12) 12.8 (0.4)* 10.2 (0.4) 10.1 (0.4) 0.1µg 10.5 (0.3) 13.04 (0.5)* 9.6 (0.35) 10.4 (0.55) 1µg 10.2 (0.4) 12.9 (0.8)* 10.1 (0.5) 10.2 (0.4) mechanical hyperalgesia (gram) 0.01µg 5.2 (0.2) 6.9 (0.2)* 5.8 (0.25)# 5.7 (0.2)# 0.1µg 5.1 (0.1) 6.6 (0.3)* 5.8 (0.2)# 5.9 (0.1)# 1µg 5.2 (0.3) 6.8 (0.2)# 5.7 (0.2)* 5.9 (0.1)# cold allodynia (%) 0.01µg 87.5 (13.9) 52.5 (10.3)# 65.0 (13.9)# 72.5 (5.9) 0.1µg 97.5 (10.3) 62.5 (7.0)# 68.8 (10.8)# 76.3 (1.8)# 1µg 96.3 (5.9) 62.5 (11.5)# 71.3 (5.8)# 77.5 (4.9)# mechanical allodynia (gram) 0.01µg 8.8 (0.55) 14.75 (0.25)* 13.4 (1.1)# 12.2 (1.8)# 0.1µg 9.3 (0.7) 14.6 (0.3)* 14.3 (0.4)# 13.1 (1.4)# 1µg 8.5 (0.8) 14.9 (0.1)* 14.4 (0.5)# 13.0 (0.2)# *have a significant difference in p<0.001 with before administration time; #shows a significant difference in p<0.05 with before administration time. the findings was extracted in terms of repeated measures anova test. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 154 should be noted that mechanical allodynia (tactile allodynia) is one of the annoying pain which always sci patients complain of it (25, 26). therefore, muscimol administration could be able to control mechanical allodynia. neuropathic pain in human has presented in the first days, especially in mechanical allodynia and those of sci which have an incomplete injury (27). although mechanisms responsible for neuropathic pain are not fully understood, but it seems that increase in glutamate and decrease in gaba content have critical role in excitotoxicity, cell death and inflammation, neuronal plasticity and hyperstimulation (28-34). therefore, using gabaa agonists like muscimol could reduce these pains. the findings obtained in the present study confirmed it. intrathecal administration of medications in sci patients could decrease their systematic effects. consequently, in recent years some methods like intrathecal pumps have been used (7, 9, 13). in this regard, the present project was evaluated the effect of intrathecal injection of muscimol on pain symptoms in a central neuropathic pain model. this method, which has favorable outcomes, has been used in controlling the acute and chronic pains. however, there are some risks aligned with using intrathecal therapy such as catheter or pumps dysfunction, catheter removal, causing inflammatory reactions, and etc (35, 36). therefore, the investigation on this issue is still on. there are just few studies, which have evaluated the effect of muscimol administration in reducing the neuropathic pain. among these studies, naik et al. revealed that using muscimol in dorsal horn of the spinal cord avoid hyperalgesia. this animal study used a peripheral injury model showed that muscimol causes to improve nerve regeneration in addition to decreasing the acute b a d c figure 1: effectiveness of different muscimol dose administration on reducing the neuropatic pain. data eas peresent as mean±sem a: heat hyperallgesia; b: mechanical hyperallgesia; c: cold allodynia; d: mechanical allodynia. **have a significant difference in p<0.001 with before administration time; *shows a significant difference in p<0.01 with before administration time. the significance level was defined in terms of two-way anova test.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 155 emergency (2014); 2 (4): 151-157 hyperalgesia (37). these researchers also displayed in another study that muscimol causes to reduce the thermal and mechanical hyperalgesia (38). in addition, baba et al showed that using muscimol leads to decrease irritability the a and c sensory fibers (39). these results support the present findings. some studies evaluated the effectiveness of this drug on chronic models. for instance, miletic et al revealed that muscimol can improve the nerve plasticity in posterior horn of the spinal cord (40). such effects aligned with sedative role of muscimol, causes to reduce the acute neuropathic pain with neuronal growth and synaptic connections, too. the outcomes of these changes lead to improve the sensory motor function. finally, it was found that using muscimol causes to decrease the neuropathic pain. moreover, the efficiency of this drug progressively reduces after 15 minutes for thermal hyperalgesia. as a result, it may be possible to use muscimol combined with a long-acting drug, endomorphine, or clonidine in treatment of neuropathic pains. of course, more studies are needed to determine the efficiency and effectiveness of this combination therapy. conclusion: the finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg causes to reduce the symptoms of neuropathic pain. nevertheless, its effectiveness gradually decreased after 15 minutes. thus, combination therapies could be an appropriate option for compensation of this limitation. however, further studies are required to confirm this hypothesis. acknowledgments: the authors appreciate the insightful cooperation of animal lab of iran university of medical sciences. conflict of interest: none funding support: this experiment was funded by iran university of med b a d c figure 2: effectiveness of various muscimol doses on reducing the neuropatic pain symptoms in corresponding times. a: heat hyperallgesia; b: mechanical hyperallgesia; c: cold allodynia; d: mechanical allodynia. the significance level was evaluated based on ancova test. no significant difference was seen among various doses in evaluated times to reduce the neuropathic pain symptoms  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 156 ical sciences. authors’ contributions: fn designed the study and my analyzed data and developed first draft of the manuscript. mh and zk inducted the animal model of sci. aj and zh contributed in were assessed behavioral tests. all authors contributed substantially to its revision and take responsibility for the paper as a whole. references: 1. mann r, schaefer c, sadosky a, et al. burden of spinal cord injury-related neuropathic pain in the united states: retrospective chart review and cross-sectional survey. spinal cord. 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neurosci. 2003;24(3):818-30. 40. miletic g, draganic p, pankratz mt, miletic v. muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the gaba transporter gat-1. pain. 2003;105(1):347-53. archives of academic emergency medicine. 2022; 10(1): e41 or i g i n a l re s e a rc h safety and adverse events related to covid-19 mrna vaccines; a systematic review seyedahmad seyedalinaghi1, amirali karimi2, zahra pashaei1, arian afzalian2, pegah mirzapour1, kobra ghorbanzadeh3, afsaneh ghasemzadeh4, mohsen dashti4, newsha nazarian5, farzin vahedi2, marcarious m. tantuoyir2,6, ahmadreza shamsabadi7, omid dadras1,8, esmaeil mehraeen9∗ 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. school of medicine, tehran university of medical sciences, tehran, iran. 3. department of nursing, khalkhal university of medical sciences; khalkhal, iran. 4. department of radiology, tabriz university of medical sciences, tabriz, iran. 5. school of medicine, islamic azad university, tehran, iran. 6. biomedical engineering unit, university of ghana medical center (ugmc), accra, ghana. 7. department of health information technology, esfarayen faculty of medical sciences, esfarayen, iran. 8. school of public health, walailak university, nakhon si thammarat, thailand. 9. department of health information technology, khalkhal university of medical sciences, khalkhal, iran. received: march 2022; accepted: april 2022; published online: 28 may 2022 abstract: introduction: knowledge of vaccine-related adverse events is crucial as they are among the most important factors that cause hesitation in receiving vaccines. therefore, we aimed to systematically review the adverse events related to the mrna vaccines reported in the literature. methods: a systematic literature search was carried out in the databases of scopus, pubmed, cochrane, and web of science. we selected original studies that explored the side effects of mrna covid-19 vaccines using a two-phase (title/abstract and full-text) screening process. results: cardiac complications were the most commonly reported severe adverse events. it appeared that systemic adverse reactions are more common after the second dose of vaccines. the number of adverse effects reported after the pfizer vaccine was higher than other vaccines, mostly due to its earlier approval and more widespread use throughout the world. cardiac adverse events had a higher prevalence but no significant association has been found between covid-19 mrna vaccines and cardiac adverse events except for myopericarditis. conclusion: vaccines play a crucial role in controlling the covid-19 pandemic and decreasing mortalities and the results of the present review acknowledge the fact that the benefits outweigh the adverse events of these vaccines. keywords: adverse effects; covid-19 vaccines; 2019-ncov vaccine mrna-1273; mrna vaccines; bnt162 vaccine cite this article as: seyedalinaghi s, karimi a, pashaei z, afzalian a, mirzapour p, ghorbanzadeh k, ghasemzadeh a, dashti m, nazarian n, vahedi f, tantuoyir mm, shamsabadi a, dadras o, mehraeen e. safety and adverse events related to covid-19 mrna vaccines; a systematic review. arch acad emerg med. 2022; 10(1): e41. https://doi.org/10.22037/aaem.v10i1.1597. ∗corresponding author: esmaeil mehraeen; department of health information technology, khalkhal university of medical sciences, khalkhal, iran. postal code: 5681761351, tel: +98-45-32426801, fax: +98-45-32422305, e-mail: es.mehraeen@gmail.com , orcid: http://orcid.org/0000-0003-4108-2973. 1. introduction the covid-19 pandemic is a global health crisis that demands enormous measures in order to be controlled. mass vaccination of the population is critical for containing it; thus, countries all over the world are attempting to vaccinate their people against this disease (1-4). vaccines operate by stimulating the body’s natural immunological response. immediately after the genetic sequence of the novel coronavirus this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 2 was uncovered, vaccine manufacturers all around the world jumped into action to develop a vaccine (5). currently available sars-cov-2 vaccines are produced using one of the following technologies: mrna-based vaccines, whole virus or inactivated virus vaccines, protein subunit vaccines, and viral vector-based vaccines (6). pfizer-biontech bnt162b2 and moderna mrna1273 are the first and only mrna-based vaccines approved by the world health organization so far and have been used in several countries. these vaccines encode a stable full-length sarscov-2 spike ectodomain, derived from the wuhan-hu-1 genetic sequence (7, 8). they are a novel-nucleic acid type of vaccine that employs genomic information such as messenger rna (mrna), a method that introduces a portion of the genetic code into human cells (9, 10). furthermore, the high level of reactogenicity of the sars-cov-2 mrna vaccines is one of their distinguishing features, provoking both local and systemic reactions observed by the majority of patients in phase 1-3 trials. additionally, the levels of systemic reactogenicity associated with sars-cov-2 mrna vaccines have generated concerns about a more serious adverse event profile in patients with underlying immunological dysregulation as these patients, who often consume immunosuppressive and biologic medications for immune-mediated inflammatory illnesses such as inflammatory bowel disease (ibd), were mostly exempted from the vaccine trials. activation of the innate immune system through pattern-recognition receptor ligation, followed by the production of inflammatory cytokines such as tumor necrosis factor, interleukin-6, and interleukin-1 is often responsible for the vaccine’s reactogenicity (11, 12). adverse drug reactions (adrs) and medication-related incidents could be fatal, likewise, the side effect of vaccines could be catastrophic. if clinical trials are not powered enough to detect the very rare events, these rare but important adverse events may go undetected. due to variances in age, race, and underlying conditions, the reported rates of adverse effects have been inconsistent across different studies. even though their safety has been established, concerns of immune-mediated disease flare-ups or new-onset inflammatory diseases following their administration have recently emerged (13-16). the vaccine adverse event reporting system (vaers), co-developed and maintained by the centers for disease control and prevention (cdc) and the united states food and drug administration (fda), serves as a national passive surveillance system for continuous monitoring of vaccine safety once it has been distributed in the market (17). the data from vaers show that the most commonly reported side effects are injection site pain, fever, headache, neck pain, nausea, vomiting, drowsiness, diarrhea, dizziness, enlarged lymph nodes, decreased alcohol tolerance, dyspnea, cough, stuffy nose, fainting, thirst, excessive sweating, sore throat, loss of appetite, insomnia, irritability, stupor, photosensitivity, eye pain, numbness in the extremities, and malaise (18-20). vaccine safety is important to the success of any vaccination effort, particularly during a pandemic. hence, with the increase in vaccination rates, it is crucial to monitor their adverse events post-vaccination. raising awareness of associated adverse events (aes) is crucial for reducing vaccine hesitancy as well as improving the safety of vaccines if necessary (21). therefore, in this study, we aimed to systematically review the adverse events related to the mrna vaccines reported in the literature. the findings could present and enhance scientific literacy across the many stakeholders and provide concise and evidence-based soltutions to the covid-19 vaccine safety concerns. 2. methods this review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. a systematic search of relevant records was carried out in the online databases using selected keywords on september 15th, 2021. 2.1. data sources we carried out a systematic search using the keywords and search queries in online databases including scopus, pubmed, cochrane, and web of science. 2.2. search strategy search strategies were constructed by two authors of the research team. search terms were connected in a highlysensitive syntax via the boolean operator or. the search strategy that was used to retieve the records in each online database is as follows: ((((((covid-19[title]) or (sars-cov-2[title])) or (sarscov2[title])) or (2019-ncov[title])) or (novel coronavirus[title])) and ((((vaccine*[title]) or (vaccination[title])) or (vaccinated[title])) or (immunization[title]))) and (((((safety[title]) or (side effect*[title])) or (adverse event*[title])) or (adverse effect*[title])) or (adverse reaction*[title])) 2.3. eligibility criteria original english articles that reported the adverse events of mrna covid-19 vaccine were included, applying the following exclusion criteria: 1) abstracts/conference abstracts or unavailability of full texts 2) ongoing clinical trials with unpublished results 3) non-original studies, including review articles, metaanalyses, protocols, and editorials this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e41 figure 1: prisma flow diagram of the systematic review. 4) studies on other types of vaccines rather than mrna vaccines, or those only reporting efficacy of mrna vaccines without reporting their adverse events 5) protocols of randomized clinical trials (rcts) and other original studies 2.4. selection of studies and data screening the endnote x9 software was used to organize the retrieved articles. search results from different databases were combined in a single endnote library and duplicates were removed. two authors independently screened the retrieved articles in two steps. first, the title and abstract of the retrieved records were screened and the ineligible articles were removed. the full texts of the remaining articles were reviewed based on the inclusion and exclusion criteria and the eligible studies were included in the final qualitative analysis of the results. 2.5. data extraction the following data were independently extracted by four researchers: first author, type of study, country of research, manufacturer of the mrna vaccine, sample population, age, gender, severe adverse events, time from the injection to the appearance of adverse events, and local and systemic adverse events.these findings were organized into a table and were used for qualitative synthesis. another author reviewed the extracted data and addressed any inconsistencies that existed between authors. 2.6. quality assessment the newcastle-ottawa scale (nos) was used to assess the quality of included studies. this criteria yields a maximum score of nine for questions regarding selection, comparability, and exposure (22). studies with poor quality assessment scores of four or less were excluded from this systematic review. 3. results our search yielded a total of 1062 studies, and two more records were identified through manual searching. after removing the 547 duplicates, 515 records remained. a total of 171 records were excluded in the title/abstract screenings, and 346 full-text reports were assessed for eligibility (344 from database search, two via manual searching). finally, 74 studies were found to be eligible for this systematic review (figure 1). the mean nos quality assessment score of the studies was 6.5. no study had a score of four or less and therefore, no study was excluded from this systematic review due to low quality score. the purpose of this study was to review and describe the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 4 findings of articles that reported safety and adverse events related to covid-19 mrna vaccines. we included articles that investigated the adverse effects of covid-19 mrna vaccines (pfizer-biontech, moderna, bnt, and bnt162b1) in the 1st, 2nd, and 3rd-phase rcts, cross-sectional, and cohort studies. 3.1. adverse reactions in both pfizer and moderna vaccines mild to moderate local and systemic adverse reactions were reported. the findings have shown that the incidence of systemic adverse reactions could increase following the second dose. also, the prevalence of systemic adverse reactions in younger adults (age group of 18-55) was higher in comparison with older adults. injection site pain and muscle pain were the most common local adverse reactions reported in studies. also, headache was the most prevalent systemic adverse reaction, followed by fatigue, myalgia, chills, and fever. other local adverse reactions included tenderness, redness, urticaria, rash and swelling, neck pain, hand numbness, erythema, induration, itching, local loss of hair, and edema. some other less common systemic adverse reactions were as follows: body aches, gastrointestinal symptoms, arthralgia, nausea, vomiting, diarrhea, dizziness, vertigo, weakness, and visual symptoms (table 1). it should be noted that adverse reactions and severe adverse events could affect all healthy, pregnant, and immunocompromised vaccine recipients. 3.2. severe adverse events (sae) in this review, severe adverse events were reported and classified into five categories including cardiac, allergic, neurologic adverse events, and adverse events that may occur in pregnant and immunocompromised patients who received covid-19 mrna vaccines. the time interval between inoculation and onset of severe adverse events varied from one hour to 84 days after the injection of the first or second dose. severe adverse events are reported as follows: -cardiac most of the reported severe adverse events were related to cardiac events. a cross-sectional study among 700 participants who received pfizer-biontech reported severe chest pain (0.4%) and acute hypertension (0.3%) after the first vaccine shot (6). a retrospective study among 113 allogeneic hematopoietic stem cell transplant recipients, who received pfizer and moderna vaccines, reported tachycardia and increased blood pressure (0.8%) (23). in a 3rd phase rct among 14134 participants who received mrna-1273 (moderna), the authors reported one case of cardiopulmonary arrest (0.007%) (24). another study on 884,828 participants who received pfizer vaccine reported myocarditis (risk ratio, 3.24 and risk difference 2.7 events per 100,000 persons) (25). a cross-sectional study on 8275 participants reported one case of acute myocardial infarction (26). another crosssectional study on 432 participants who received the moderna vaccine reported chest pain (1.85%) and syncope (0.93%) (27). likewise, in another cross-sectional study on 803 participants who had received pfizer vaccine, chest pain (1.12%) and syncope (0.12%) were reported as serious adverse events (20). another cross-sectional study on 190 patients who had received the pfizer vaccine reported one case of supraventricular tachycardia (1%) and one case of decompensated heart failure (1%) (28). in a 2nd phase rct on 43,448 participants, 21720 of whom received bnt162b2 vaccine, one case of paroxysmal ventricular tachycardia (0.004%) was reported (29). -pregnancy among studies included in our review, two studies were conducted on pregnant women who had received mrna vaccine during their pregnancy, and one study on 35691 pregnant women reported possible serious adverse effects as follows: spontaneous abortion (46 cases; 37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), stillbirth, premature rupture of membrane, and vaginal bleeding with 3 reports for each, and no congenital anomalies were documented (30). in another study on pregnant women, the rates of adverse pregnancy outcomes among 133 women who received at least 1 dose of the covid-19 vaccine in pregnancy were similar to that of unvaccinated pregnant women regarding stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal highdependency unit or intensive care admission (6.0% vs 4.0%), and neonatal intensive care unit admission (5.3% vs 5.0%). in addition, three fetal abnormalities, including spina bifida, ventriculomegaly, and hydronephrosis, were reported. the spina bifida case was diagnosed before the pregnant woman received the first dose of the vaccine. the ventriculomegaly case was diagnosed at 37 weeks gestation and was isolated, with no associated brain abnormalities, as confirmed by fetal brain magnetic resonance imaging. the hydronephrosis was mild, with no associated abnormality at birth (31). -allergic some studies reported rare allergic adverse events such as swelling of eyelids, severe allergic reaction of eyelids, anaphylactoid reactions, and angioedema (9, 24, 27, 32, 33). in a cross-sectional study conducted on 700 participants who received pfizer vaccine, two cases with swelling and severe allergic reaction of eyelids were reported (1). in a similar cross-sectional study on 432 participants who received moderna vaccine, swelling in the mouth or throat (0.46), asthma exacerbation (0.46%), swelling of lips (0.23%), and anaphylaxis (0.23%) were observed (27). also, in the 3rd phase rct among 14,134 white and black usa residents who received this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e41 moderna, hypersensitivity reactions were reported in 1.5% of participants (24, 27). two cross-sectional studies reported allergic reactions in 2.2% (15 out of 688) of participants and two cases of angioedema (0.4%) (2 out of 474) within 48 hours of vaccine injection, respectively (34, 35). between december 14, 2020, and january 18, 2021, based on cdc reports, after vaccination with 9,943,247 pfizerbiontech doses and 7,581,429 moderna doses in the us (cdc unpublished data, february 2021), the risk of anaphylaxis was 4.7 cases/per-million-dose for pfizer-biontech, and 2.5 cases/per-million-dose for moderna vaccine. overall, since late january 2021, cdc reported 66 cases of anaphylaxis, including 47 cases after the pfizer-biontech vaccine and 19 cases after the moderna vaccine. all these 66 persons were treated in health care settings. the median time to event was 6 minutes (range, <1-45 minutes). almost all cases recovered in the follow-up and no deaths from anaphylaxis after vaccination with either product were reported (36). in another cross-sectional study, the authors investigated the adverse effects of 578,835 doses of the mrna-based vaccines in the japanese population, 733 adverse event following immunizations or aefis (85 males [12%], 647 females [88%], 1 unknown [< 1%]) were reported. among these, there were 181 (first dose: 177; second dose: 3; unknown: 1) suspected anaphylaxis reports, resulting in a reporting rate of 31.3/100,000 doses. in 171 of 181 cases, women developed suspected anaphylaxis and anaphylactoid symptoms within ≤5min or >30 min of injection (33). neurologic in total, 10 studies reported adverse neurologic events among healthy patients and patients with prior neurologic diseases. these adverse events were bell’s palsy, herpes zoster, ischemic stroke, new or worsening neurological symptoms (muscle weakness, walking difficulty, gait instability, visual problems, pain, sensory disturbances, and sphincteric problems) among patients with underlying neurological diseases, guillain-barre syndrome, seizure, loss of consciousness, fainting, syncope, leg paresthesia, functional syndromes, acute transverse myelitis, and lumbar radiculopathy exacerbation (20, 24-27, 29, 37-40). a 3rd-phase rct on 14134 who received moderna reported three cases of bell’s palsy in both the vaccine group (<0.1%) and placebo group (<0.1%) (24). in addition, one case of bell’s palsy was reported 11 days after the 1st dose of pfizer vaccine in a cross-sectional study. the unadjusted 15-day rate of adverse events per 100,000 residents following the first dose of vaccine was the same in both vaccinated and unvaccinated groups for bell’s palsy (26). herpes zoster was observed at the rate of 15.8 events per 100,000 persons among 884,828 who received the pfizer vaccine (25). other neurological symptoms were as follows: 73 participants (16.7%) who had a history of rare neuro-immunological disorders reported new or worsening neurological symptoms following pfizer and moderna vaccination (37), 36 participants (15.1%) with multiple sclerosis who received pfizer covid-19 vaccine reported new or worsening neurological symptoms (muscle weakness, walking difficulty, gait instability, visual problems, pain, sensory disturbances and sphincteric problems) (41), guillainbarre syndrome (gbs) was seen in a healthy male 4 days after the second dose of moderna (39), there was one case of the seizure (0.23%) after receiving moderna vaccine (27), food intolerance (0.25%), loss of consciousness or fainting (0.25%), seizures (0.12%), and syncope (0.12%) among 803 participants who had received pfizer (20), and one case of leg paresthesia in a 2nd-phase rct of pfizer vaccine (29). in addition, a cohort study on 704,003 participants who received pfizer vaccine reported 33 (0.005%) serious adverse events, 17 of which (51.5%) were neurologic (2.4/100,000 doses) in the first 30 days after vaccination, however, no death was reported due to the complications. among those 17 patients, seven cases had seizures (0.99/100,000 doses); four mentioned functional syndromes (0.56/100,000 doses); three had gbs (0.43/100,000 doses); two were diagnosed with acute transverse myelitis (0.28/100,000 doses); and one case was consistent with lumbar radiculopathy exacerbation (0.14/100,000 doses) (40). immunocompromised patients a retrospective study on 113 allogeneic hematopoietic stem cell transplant recipients who received pfizer-biontech and moderna vaccine reported one case of axillary lymphadenopathy, one case of increased blood pressure, and tachycardia. in addition, neutropenia, thrombocytopenia, lymphopenia, and eosinophilia were observed in 13.3%, 11.5%, 8.8%, 4.4% of vaccine recipients 20.5, 34, 19.5, and 28 days after vaccination. in addition, they reported new chronic graft-versus-host disease (gvhd) (9.7%) or worsening chronic gvhd (3.5%) 3 to 48 days after vaccination. also, two patients experienced both new and worsening gvhd symptoms. one patient with a previous history of chronic gvhd was hospitalized (23). another study on 80 allogeneic hematopoietic cell transplantation recipients or cd19-based chimeric antigen receptor t-cell (cart) therapy patients who received pfizer vaccine reported cytopenia (12% of the patients after the 1st dose and 10% of the patients after the 2nd dose), graft-versus-host disease exacerbation (4.5%), and a single case of impending graft rejection as possible vaccination adverse effects within 1st week of injection (42). one cohort study on 741 solid organ transplant recipients who received pfizer or moderna vaccines, reported one case of acute rejection after the 2nd dose, and infection (3% after 1st dose and <0.01% after 2nd dose) within 7 days post-vaccination. lao, in a cohort study that was conducted on 151 cancer patients and 54 healthy patients who received pfizer or moderna vaccines, reported only one case this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 6 of deranged liver function test 3 weeks after the 1st dose in the control group (43). in a study of 373 cancer patients who received pfizer-biontech or moderna vaccine, eight patients reported severe adverse events as follows: chest pain (0.3%), dyspnea (1.1%), urosepsis(0.3%), febrile neutropenia (0.3%), and lymphadenopathy (0.5%) within seven days after injection, and venous thromboembolism (vte) (0.3%) within seven days after vaccination (44). 4. discussion in this review, we synthesized the safety data and side effects of covid-19 vaccines from 74 published articles. it appeared that the adverse reactions were often mild to moderate with few serious adverse events. at least one case of serious adverse events was reported in 30 articles. most studies had investigated the adverse events after the pfizer-biontech vaccine, while few studies had studied moderna (mrna-1273) or both mrna vaccines’ adverse effects. the number of adverse effects reported after the pfizer vaccine was higher, but this was mostly due to its earlier approval and more widespread uptake across the world. the reported severe adverse events associated with the covid-19 vaccines were more frequently related to allergic events, neurological events, and cardiovascular implications including chest pain, myocardial infarction, acute hypertension, tachycardia, myocarditis, syncope, supraventricular tachycardia, decompensated heart failure, and paroxysmal ventricular tachycardia. the majority of vaccine recipients reported at least one local or systematic side effect after inoculation with the mrna covid-19 vaccine. albeit, all reported side effects were minor and had a short duration. local and systemic adverse reactions were found to be more prevalent after the second dose. common adverse reactions were injection site pain, headache, muscle pain, myalgia, chills, and fever. the systemic adverse reactions had moderate intensity in the young age group in comparison with those who were 65 years old or older. the majority of adverse reactions like fatigue, joint pain, muscle pain, and headache were reported by the younger age group (18-55 years) and obviously, less reported by the older adults. these findings are in line with findings of a similar study that assessed 11 clinical trials of covid-19 vaccines (45). ten studies in this review reported possible cardiac adverse effects. in those who received pfizer vaccine, severe chest pain, acute hypertension, tachycardia, myocarditis, syncope, supraventricular tachycardia, decompensated heart failure, and paroxysmal ventricular tachycardia were reported. on the other hand, increased blood pressure, tachycardia, cardiopulmonary arrest, chest pain, and syncope were reported in moderna receivers. in addition, acute myocardial infarction was documented after mrna vaccine inoculation. no significant association has been found between covid19 mrna vaccines and cardiac adverse events mentioned above, except for myopericarditis. the findings of a systematic review conducted to investigate the safety and adverse events of covid-19 vaccines among children and adolescents were in line with our findings; 27 cases of approved myocarditis or pericarditis were found in 7 assessed studies (including one rct, two case series, and four case reports), all of which occurred after the 2nd dose of pfizer vaccine. this systematic study’s findings show an incidence rate of 0.008% for myopericarditis in adolescents aged 16 to 17 years old and also 0.01% in adolescents aged 12 through 15 years following the second dose (25, 46). in another study, 16 cases of myocarditis, pericarditis, and myopericarditis were reported after injection of both types of mrna vaccines. these severe cardiac adverse effects occurred after the first vaccine dose in six cases (35%), after the second dose in ten cases (59%), and after both doses in one case (6%). the median time to event was 14 days (range 1–28) after the first vaccination and 3 days (range 1–17) after the second shot (47). similar findings were reported in a systematic review that investigated the cardiac adverse outcomes after covid-19 vaccine injection. in total, 42 acute myocardial infarction (ami) and 35 myocarditis cases were reported after covid-19 vaccination and 41 (98%) and 31 (89%) of these cases had been vaccinated by mrna vaccines, respectively. the majority were men, and myocarditis cases were younger than ami patients. myocarditis was observed after an average of 3 days after vaccination, while ami mostly occurred after an average of 1 day. thirty-five (83%) myocarditis and six (33%) ami patients developed symptoms after their second dose. the majority of the myocarditis (83%) and ami patients (86%) had received the pfizer biontech vaccine. the remaining patients with myocarditis received the moderna (14%) and janssen vaccine (2%) vaccines, while ami patients had received the oxford-astrazeneca vaccine (11%) and moderna vaccine (3%) (48). these findings were consistent with our study indicating a strong possibility of myocarditis (risk ratio, 3.24; [ci95% 1.55-12.44]) after bnt162b vaccination; however, this risk was significantly lower in comparison with myocarditis after sars-cov-2 infection, which is 18.28 (95% confidence interval [ci95% 3.95-25.12]) (25). in addition, some included studies in our review had reported cases of severe chest pain and acute myocardial infarction. it seems that the rate of adverse pregnancy outcomes is no different between vaccinated and unvaccinated pregnant women and no association between mrna vaccines and pregnancy outcomes was found. this finding was consistent with the findings of other systematic reviews, which were conducted on pregnant women who received either of the mrna vaccines. no increased risk of adverse obstetrical or neonatal outcomes was reported and the proportion of inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e41 fant outcomes reported, including spontaneous abortions, stillbirth, induced abortion ectopic pregnancy, and spontaneous abortions, were similar to non-vaccinated pregnant women. also, safety data indicated that pregnant and lactating populations experienced vaccine-related reactions at similar rates to the general population (49, 50). the findings of included studies showed that those who have received the pfizer vaccine are more likely to have allergic reactions than those who received moderna vaccine. a systematic review including 26 articles, involving 26,337,421 mrna sars-cov-2 vaccine recipients (14,505,399 doses of pfizer-biontech and 11,831,488 doses of moderna) reported similar results. this study reported that vaccination with pfizer-biontech vaccine resulted in higher rate of anaphylactic reactions compared to moderna vaccine (9.31/permillion-dose and 3.42/per-million-dose). this study also reports a lower incidence of non-anaphylactic reactions with pfizer compared to moderna (75.27/per-million-doses, versus 99.01/per-million-doses administered) (51). in another systematic review and meta-analysis, which investigated the risk of allergic and severe adverse events, the incidence rate of anaphylaxis was reported as 7.91/per-million-cases (among 41,000,000 patients) (52). the post-covid-19 vaccination neurological adverse events are relatively rare and the causal association between neurological symptoms and vaccination is uncertain. bell’s palsy was reported as one of the neurological adverse events in two assessed studies (26, 53). however, no significant differences in bell’s palsy incidence were reported between vaccinated and unvaccinated individuals. a review has also acknowledged that most bell’s palsy cases were associated with mrna vaccines. no difference was found between clinical features of vaccine-associated bell’s palsy and conventional types and the pathogenesis remains unclear (54). in addition, some neurological adverse events including guillain-barre syndrome, herpes zoster, seizure, loss of consciousness or fainting, syncope, leg paresthesia, and acute transverse were reported; the causal association of adverse events and vaccination or coincidence of them must be carefully assessed. most of the covid-19 vaccine randomized trials have excluded those with immunocompromised conditions, so there is limited data available about adverse events in individuals with autoimmune disease and cancer. however, in transplant recipients, graft-versus-host disease exacerbation, and impeding graft rejection were reported as possible vaccination adverse events. no significant difference was reported between severe complications in cancer patients and healthy patients, as the control group, who received pfizer or moderna vaccines (43, 44). the adverse events of vaccination should continuously be monitored to identify any new issues in the safety of vaccines, which require investigations. in other words, while assessing the safety of vaccines, any unexpected or unusual patterns in vaccinated individuals, which have a higher rate than the general population should be considered. in this study, the most commonly reported serious adverse events were cardiac events, additional studies are recommended to investigate the association between vaccination and cardiac complications. also, in order to collect data on the clinical, cardiological, neurological, and immunological profile of the covid-19 vaccinated population, cohort studies could further assess the frequency of adverse events in the general population. 5. conclusion some severe adverse events were observed among the recipients of mrna vaccines, but a direct relationship between the vaccines and adverse events has not been clearly established for the adverse events, except for myopericarditis. the rate of severe adverse effects is low and obviously, the benefits of receiving vaccines in preventing severe covid-19 and death outweigh the possible rare adverse events of the covid-19 vaccines. therefore, healthcare officials should enlighten people on the safety of the vaccines, in this case mrna vaccines, to avoid further hesitations in covid-19 vaccination, which may endanger the lives of people and pose a huge burden on the healthcare system. 6. declarations 6.1. acknowledgments this systematic review was supported by tehran university of medical sciences with the grant no. 1400-3-119-55855 and the ethics code: ir.tums.ikhc.rec.1400.510. 6.2. data availability the data is at the disposal of the corresponding author of the article and it it can be made available to the researchers upon request. 6.3. authors’ contributions (1) the conception and design of the study:esmaeil mehraeen, seyedahmad seyedalinaghi (2) acquisition of data:amirali karimi, zahra pashaei (3) analysis and interpretation of data: pegah mirzapour, arian afzalian (4) drafting the article: kobra ghorbanzadeh, afsaneh ghasemzadeh, mohsen dashti, newsha nazarian, farzin vahedi, marcarious m. tantuoyir, ahmadreza shamsabadi (5) revising it critically for important intellectual content: seyedahmad seyedalinaghi, omid dadras (6) final approval of the version to be submitted: all authors this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 8 6.4. funding and supports this research received a grant from tehran university of medical sciences (grant no. 1400-3-119-55855). 6.5. competing interests the authors declare that there is no conflict of interest regarding the publication of this manuscript. 6.6. availability of data and material the authors stated that all information provided in this article could be shared. 6.7. consent to publication not applicable 6.8. ethics approval and consent to participate the present study was approved by tehran university of medical sciences with the ethics code: ir.tums.ikhc.rec.1400.510. references 1. amimo f, lambert b, magit a, hashizume m. a review of prospective pathways and impacts of covid-19 on the accessibility, safety, quality, and affordability of essential medicines and vaccines for universal health coverage in africa. globalization and health. 2021;17(1):42. 2. gubernot d, jazwa a, niu m, baumblatt j, gee j, moro p, et 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shashar m, lellouche j, yana m, yakubovich d, sharon n. occurrence of bnt162b2 vaccine adverse reactions is associated with enhanced sars-cov-2 igg antibody response. vaccines. 2021;9(9):977. 80. quiroga b, sánchez-álvarez e, goicoechea m, de sequera p. covid-19 vaccination among spanish nephrologists: acceptance and side effects. journal of healthcare quality research. 2021;36(6):363-9. 81. pimpinelli f, marchesi f, piaggio g, giannarelli d, papa e, falcucci p, et al. fifth-week immunogenicity and safety of anti-sars-cov-2 bnt162b2 vaccine in patients with multiple myeloma and myeloproliferative this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 12 malignancies on active treatment: preliminary data from a single institution. journal of hematology & oncology. 2021;14(1):81. 82. panda ds, giri rk, nagarajappa ak, basha s. covid-19 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and immunogenicity of two rna-based covid-19 vaccine candidates. the new england journal of medicine. 2020;383(25):2439-50. 92. skroza n, bernardini n, tolino e, proietti i, mambrin a, marchesiello a, et al. safety and impact of anti-covid19 vaccines in psoriatic patients treated with biologics: a real life experience. journal of clinical medicine. 2021;10(15):3355. 93. rotondo c, cantatore fp, fornaro m, colia r, busto g, rella v, et al. preliminary data on post market safety profiles of covid 19 vaccines in rheumatic diseases: assessments on various vaccines in use, different rheumatic disease subtypes, and immunosuppressive therapies: a two-centers study. vaccines. 2021;9(7):730. 94. chen yw, tucker md, beckermann ke, iams wt, rini bi, johnson db. covid-19 mrna vaccines and immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. european journal of cancer (oxford, england : 1990). 2021;155:291-3. 95. chevallier p, coste-burel m, le bourgeois a, peterlin p, garnier a, béné mc, et al. safety and immunogenicity of a first dose of sars-cov-2 mrna vaccine in allogeneic hematopoietic stem-cells recipients. ejhaem. 2021;2(3):520-4. 96. chu l, mcphee r, huang w, bennett h, pajon r, nestorova b, et al. a preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mrna-1273 sars-cov-2 vaccine. vaccine. 2021;39(20):2791-9. 97. efrati s, catalogna m, abu hamad r, hadanny a, barchaim a, benveniste-levkovitz p, et al. safety and humoral responses to bnt162b2 mrna vaccination of sars-cov-2 previously infected and naive populations. scientific reports. 2021;11(1):16543. 98. el-shitany na, harakeh s, badr-eldin sm, bagher am, eid b, almukadi h, et al. minor to moderate side effects of pfizer-biontech covid-19 vaccine among saudi residents: a retrospective cross-sectional study. international journal of general medicine. 2021;14:1389-401. 99. frenck rw, jr., klein np, kitchin n, gurtman a, absalon j, lockhart s, et al. safety, immunogenicity, and efficacy of the bnt162b2 covid-19 vaccine in adolescents. the new england journal of medicine. 2021;385(3):239-50. 100. golan y, prahl m, cassidy ag, gay c, wu ahb, jigmeddagva u, et al. covid-19 mrna vaccination in lactation: assessment of adverse effects and transfer of antisars-cov2 antibodies from mother to child. medrxiv : the preprint server for health sciences. 2021. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e41 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic tom t. shimabukuro. (55) usa/ white crosssectional pb, m 35,691 16 to 54 years female (100) spontaneous abortion, preterm birth, small size for gestational age n/a injection-site pain headache, myalgia, chills, and fever abuhalaweh, s. (56) usa observational cohort pb 491 >70 years male (67) female (33) n/a n/a injection site pain, muscle pain fatigue, headache, arthralgia, fever abuhammad, o. (57) usa crosssectional pb 409 n/a n/a no severe adverse reaction 1.39 ± 1.12 days injection site pain or arm numbness fatigue, myalgia, headache al ghafri, t. s. (58) oman crosssectional pb 753 62 males (54.1), female (45.9) no severe adverse reaction 2 days pain and tenderness fever and body aches al khames aga, q. a. (9) usa crosssectional pb 700 18 and above male (51.6), female (48.4) tenderness or swollen lymph nodes, severe allergic reaction of eyelids, severe chest pain, acute hypertension, acute hyperglycemia 1.903±2.128 days pain, redness, urticarial, and swelling at the site of the injection fatigue, body pain, headache, muscle pain, fever, and gastrointestinal effects alhazmi, a. (10) saudi arabia crosssectional pb 533 18 to 70 years male (43), female (57) hospitalization due to side effect 1-5 days pain, and redness at the site of injection fatigue, fever, chills, and headache ali, h. (23) usa retrospective study pb 113 66.5 male (69), female (31) axillary lymphadenopathy, increased blood pressure, and tachycardia 26 days injection site pain, injection-site rash, and swelling myalgia, arthralgia, fatigue, nausea, vomiting, diarrhea, and headache anderson, e. j. (59) usa rct first phase m 40 56–70 male (48), female (52) paronychia 2 days injection-site pain headache, fatigue, fever, myalgia, and chills, andrzejczakgrządko, s. (18) poland crosssectional pb 196 20-84 male (15), female (85) enlarged lymph nodes, decreased alcohol tolerance n/a injection site pain, shoulder pain, muscle aches, neck pain, and hand numbness headache, fever, chills, nausea, vomiting, drowsiness, diarrhea, and dizziness baden, l. r. (24) usa/white and black rct third phase m 14134 51.4 male (52.7), female (47.3) cardiopulmonary arrest, bell’s palsy n/a injection site pain, erythema, induration, and tenderness n/a barda, n. (25) usa rct pb 884828 36 male (52), female (48) myocarditis, lymphadenopathy, appendicitis, arrhythmia, deep-vein thrombosis, myocardial infarction, myocardial infarction, intracranial hemorrhage, pulmonary embolism, herpes zoster n/a n/a vertigo this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 14 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic bardenheier, b. h. (26) usa/white, black crosssectional pb 8275 18 and above male (38.1), female (61.9) acute myocardial infarction, bell’s palsy, stroke, ischemic, venous thromboembolism, and pulmonary embolism 15-day n/a n/a benda, m. (60) austria crosssectional pb 259 65.1 male (57.5), female (42.5) no severe adverse reaction 7-day injection site pain fatigue, severe headache, severe general muscle pain, and fever blakeway, h. (31) uk/ afrocaribbean, asian ethnicity, and white retrospective cohort study pb, m 1328 18-40 female (100) spina bifida, ventriculomegaly, hydronephrosis, fetal abnormalities, postpartum hemorrhage n/a n/a n/a caminati, m. (61) italy crosssectional n/a 253 n/a n/a no severe adverse reaction n/a n/a n/a levy i. (62) israel prospective study pb 143 49.8±11.5 years male and female n/a 21 days local pain fatigue, headache, fever, li j. (63) uk rct pb 463 57·8±4.7 male (54) female (46) n/a 28 days and 84 days mild to moderate pain at the injection site, injection-site redness, or swelling. fever, fatigue, headache, and muscle and joint pain li j. (32) china prospective study n/a n/a n/a n/a anaphylactic reaction (1/100000) n/a pain at the injection site, injection-site redness or swelling fever, fatigue, headache, and muscle and joint pain li x. (64) uk cohort study n/a 126661070 n/a male (49.5) female (50.5) hemorrhagic and non-hemorrhagic stroke, pulmonary embolism, bell’s palsy, immune thrombocytopenia, guillain-barre syndrome, and disseminated intravascular coagulation n/a n/a n/a ligumsky h. (65) israel retrospective cohort study pb 326 66 male (37.7) female (62.3) n/a 40 days local pain (n = 64, 19.6%) weakness (17.5) myalgia (12.6) headache (6.4) liu x. (66) china rct first phase pb 296 51 male (16.4) female (83.6) n/a 7 days after the 1st or 2nd dose pain, redness, swelling, induration headache, fatigue, joint pain, muscle pain, chills, nausea, anorexia, diarrhea, vomiting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2022; 10(1): e41 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic lotan i. (37) usa crosssectional pb, m 438 51 male (16.4) female (83.6) new or worsening neurological symptoms n/a local reactions, including pain, redness, swelling at the injection site muscle weakness, visual symptoms, gait instability, increased pain, sensory disturbances, sphincteric problems lotan i. (41) israel crosssectional pb n/a 42 male (24) female (76) new or worsening neurological symptoms (muscle weakness, walking difficulty, gait instability, visual problems, pain, sensory disturbances, sphincteric problems) n/a pain/redness/ swelling at the injection site generalized muscle pain, headache, dizziness, fever, chills, fatigue, maeda k. (67) japan present prospective observational study pb 225 41.8 male (30.2) female (69.8) n/a 28 days site pain systemic fever, headache, and fatigue mascellino mt. (68) brazil n/a pb, m 9000 n/a male (55) female (45) n/a 28 days a small pinched pain at the injection site, a little bit of redness fatigue, headache, muscle, and joint pain, and fever massoud f. (69) kuwait crosssectional n/a 111 n/a n/a n/a n/a pain at the injection site (43.8) fatigue (46.9), headache (34.4), myalgia (50) matarneh as. (39) qatar crosssectional pb, m n/a n/a n/a guillain-barre syndrome 4 days n/a upper extremity weakness and numbness four days following the vaccine. mathioudakis ag. (70) uk crosssectional pb, m 532 45 n/a n/a n/a pain, swelling, tenderness, redness, itching, or other fever, skin rash, shortness of breath, tingling in the mouth, face, body/extremities, swelling in the face or mouth, generalized swelling, anaphylaxis, tiredness or fatigue, flu-like illness mcmurry r. (71) usa cohort study pb, m 31029 n/a n/a n/a within 7,14,21 days local pain and swelling fatigue, fever, chills, myalgia, arthralgia, headache, lymphadenopathy, erythema, diarrhea, vomiting, facial paralysis, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 16 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic menni c. (72) usa prospective observational study pb 1607620 50·6 male (38·4) females (61·6) n/a within 8 days pain, swelling, tenderness, itch, swollen armpit glands, redness, warmth, bruising, rash, skin burning, headache, fatigue, chills and shiver, diarrhea, fever, arthralgia, myalgia, nausea, red welts on face and lips modenese a. (73) italy observational study pb 76 48.4 males (19) females (81) n/a 4 weeks pain sensation at the injection site 73.6% redness in the injection site asthenia and sleepiness, chills, 32%, myalgia and arthralgia, 31% for headache/ migraine, and 18% for fever, diarrhea, erythema, abdominal pain, itch, and vertigo hall vg (74) toronto, canada prospective study m 127 66.2 male (69.3) female (30.7) varicella-zoster virus reactivation (0.78%), fever and pruritic rash (0.78%), hospitalization (0.78%) within 7 days pain, erythema, swelling fever, headache, fatigue, myalgia, arthralgia, chills, hatmal mm (75) jordan crosssectional pb, m 612 18 and above n/a n/a within 4h to three days pain, swelling fatigue, headache, sleepiness, laziness, chills, myalgia, joints pain, fever, dizziness, decreased sleep quality, numbness in limbs, tingling in limbs, dry or sore throat, nausea, sweating, abdominal pain, irregular heartbeats, clogged nose, runny nose, haziness, chest pain, dyspnea, cough, diarrhea, abnormal blood pressure, allergic reactions, itchy, swollen ankles and feet, vomiting. kadali rak. (27) usa crosssectional m 432 1880 years old male (10.4) female (89.6) seizures (0.23%), chest pain (1.85%), syncope (0.93%), swelling in the mouth/throat (0.46%), asthma exacerbation (0.46%), swelling of lips(0.23%), anaphylaxis (0.23%) n/a pain, swelling, itching, rash, lymphadenopathy, skin discoloration, bleeding, weakness, headache, chills, fever, sweating, dizziness, flushing, myalgia, arthritis, muscle stiffness/spasm, nausea, decreased appetite, diarrhea, abdominal pain, heartburn, vomiting, constipation, swallowing, decreased sleep quality, anxiety, decrease in memory, depression, manic mood changes, psychological stress, brain fogging or confusion, incoordination, extremity weakness, fainting, seizures, herpes or shingle-like lesions, eye pain, runny nose, ringing sensation in the ears, ear pain, blurred vision, flashing lights, changes in hearing, double vision, nose bleed, bleeding gums, hoarseness, palpitations heart, blood pressure changes, chest pain, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2022; 10(1): e41 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic syncope, shortness of breath, and cough, hives, atopic eczema, fever, swelling in the mouth/throat, asthma exacerbation, anaphylaxis, burning with urination, frequent urination, blood in urine, urinary incontinence renuka a.k. kadali. (20) usa crosssectional pb 803 18-90 years old male (13.4) female (86.6) food intolerance (0.25%), loss of consciousness /fainting (0.25%), seizures (0.12%), chest pain (1.12%), syncope (0.12%) n/a sore arm/pain, swelling at the injection site, itching, lymphadenopathy rash, skin discoloration, bleeding, loss of hair locally soreness, fatigue, myalgia, headache, chills, fever, joint pain, nausea, muscle spasm, sweating, dizziness, flushing, feelings of relief, brain fogging, anorexia, localized swelling, decreased sleep quality, itching, tingling, diarrhea, nasal stuffiness, palpitations kim t. (76) republic of korea crosssectional 2574 20 to ≥60 male (24.7) female (75.2) none <3 hour-≥48 hour local tenderness/erythema/ heating sensation, edema general myalgia, febrile sensations, chills, fatigue, rash, headache, arthralgia, dizziness, nausea, vomit, pruritus, dyspnea miloslavkluger. (35) czech republic crosssectional pb, m 474 n/a male (25.7) female (73.6) unknown (0.6) severe side effects (0.4%), angioedema (0.4%) n/a injection site pain, injection site swelling, injection site redness, ulcers, vesicles, blisters, angular cheilitis, white/red plaque, oral paresthesia, taste disturbance, halitosis, bleeding gingiva, swollen mucosa, rash, urticarial, angioedema fever, chills, headache/fatigue, muscle pain, joint pain, nausea, lymphadenopathy iguchi, t. (33) japan crosssectional pb 578,835 doses and 733 adverse events 22-56 years old male (12) female (88) 181 cases of anaphylaxis and anaphylactoid symptom ≤5min ->30,min n/a anaphylaxis and anaphylactic symptoms this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 18 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic a. riad. (77) czech republic/south moravian crosssectional pb 877 43 male (11.6) female (88.4) n/a 1-3 days injection site pain and redness, labial blisters, plaque, bleeding gingiva, halitosis, lymphadenopathy fatigue, headache, muscle and joint pain, chills, rash, nausea, fever a. riad. (78) slovakia/slovak crosssectional pb 522 37.77±11 male (23) female (77) n/a 1-3 injection site pain, swelling, and redness, oral side effects, lymphadenopathy fatigue, chills, muscle, and joint pain, headache, malaise, fever, nausea, rash y. rechavi. (79) israel/arabs cohort study pb 136 40.09 male (34) female (66) n/a n/a injection site pain, swelling, and redness about 23 patients in 1st dose and 71 in the 2nd one r. ram. (42) israel/arabs cohort study pb 80 65 male (55) female: (45) gvhd exacerbation (4.5%) 1st week vasculitis rash on the leg after allogeneic hct, arthralgia, cytopenia, fasciitis, humoral or cellular response b. quiroga. (80) spain/european cohort study pb 708 44±11 male (35) female (65) n/a n/a a local reaction followed by myalgia tiredness, headache k. polewska. (28) poland/jewish crosssectional pb 190 68 male (64.7) female (35.3) supraventricular arrhythmia (n=2), covid after 1st dose (n=2), covid after 2nd dose (n=3), pneumonia (n=1), dialysis peritonitis (n=1), catheter infection (n=1), deterioration of glycemic control (n=2), decompensated heart failure (n=1) 7 days for local 1-3 days systemic 30days for severe adverse effects local site reaction, pain, shoulder pain, sinusitis fatigue, muscle pain, joint pain, headache, chills, increased sweating, change in smell and taste, deterioration of glycemic control, dizziness f. polack. (29) 152 sites worldwide/ white, black or african american, hispanic or latinx rct second phase pb 43,448 52 all >16 male (51) female (49) shoulder injury, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, right leg paresthesia 7days for local injection site pain (1 severe), redness, swelling, lymphadenopathy fatigue, headache, fever, chills f. pimpinelli. (81) italy/european cohort study pb 92 n/a male (53.3) female (46.7) n/a n/a pain, tenderness fever, headache, malaise, myalgia, chills m. i. parvej. (34) bangladesh/ indo-aryan crosssectional n/a 1529 18 and above male (66) female (34) thrombosis (0.15%) allergy (2.2%) 2 days pain in the injection site fever, muscle pain, headache, allergy, itching, diarrhea this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 19 archives of academic emergency medicine. 2022; 10(1): e41 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic a. park. (16) korea/asian crosssectional pb 27368 20 and above male (10) female (90) dyspnea (0.025) 24 hrs pfizer(first dose): local pain pfizer(second dose): local pain pfizer(first dose): fever, chills, myalgia, headache, nausea, vomiting pfizer(second dose): fever, chills, myalgia, headache, nausea, vomiting d. s. panda. (82) india/indoaryan crosssectional n/a 29 18 and above male (68.8) female (31.2) n/a n/a n/a fever, headache m. t. ou. (83) usa prospective cohort m 741 60 male (43) female (57) acute rejection of graft after 2nd dose (0.1%) infection (after 1st dose (0.4%) and after 2nd dose (0.1%)) <7 days pain in injection site fatigue, headache oh hk. (84) korea/asian retrospective study pb 3586814 n/a n/a n/a n/a n/a myalgia, fever, headache j. moralesnunez. (85) mexico/hispanic cohort study pb 303 45±12 male (40.9) female (59.1) n/a n/a rhinorrhea, dysgeusia, chest pain myalgia, shivers, arthralgia, fever, irritability, odynophagia, cough, headache, diarrhea l. monin. (43) uk/white and black cohort study pb 205 73 cancer 40.5 healthy male (52) female (48) deranged liver function test grade 4 (0.5%) 3 weeks after 1st dose injection site pain, erythema, swelling, lymphadenopathy flue like symptoms, fatigue, headache, chills, arthralgia, nausea or vomiting, fever, diarrhea noémietissot. (86) france prospective cohort pb 311 55.4 ± 6.4 male (40) female (60) n/a between 21 and 28 days injection site symptoms pain and erythema fever chills joint pain fatigue muscle pain headache emanuel zitt. (87) austria cohort study pb 50 67.6 ± 14 male (68) female (32) n/a 7 days pain fever chills joint pain fatigue muscle pain headache xiaomoxiong. (88) usa cohort study pb, m 8,976 18–64 years male (21.4) female (78.6) death (2.7%), life-threatening illness (2.7%), permanent disability (1%), hospitalizations (7.1%) 7 days injection site pain pyrexia chills dizziness fatigue nausea headache pyrexia, pain in extremity, dyspnea wi ym. (89) korea cohort study pb 80 35.83 ± 10.99 male (31) female (69) n/a after the first and second week pain, redness/swelling lymphadenopathy vomiting, nausea, fatigue, chills, fever, myalgia, arthralgia werbel wa. (90) usa cohort study pb, m 12 57 male (55) female: (45) n/a 14 days pain, redness/swelling fatigue, chills, fever, myalgia, diarrhea, headache edward e. walsh. (91) usa rct first phase pb 195 35 male (42) female (58) n/a 7 days pain, redness/swelling fever, fatigue, chills this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. seyedalinaghi et al. 20 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic alfred chung pui so. (44) uk retrospective cohort pb, m 373 56 male (37.5) female (62.5) chest pain(0.3%), dyspnea(1.1%)„ urosepsis(0.3%)„ vte(0.3%) 7 days pain at injection site/sore arm, erythema vomiting, nausea, fatigue, chills, fever, myalgia, arthralgia, diarrhea, dizziness, lymphadenopathy, anorexia, paresthesia, abdominal pain novena skroza. (92) usa cohort study pb 436 57.26 male (60) female (40) n/a 10 days n/a n/a tom t. shimabukuro. (30) usa cohort study pb, m 35,691 27.43 female 100 n/a 14 days after pain, redness/swelling vomiting, nausea, fatigue, chills, fever, myalgia, arthralgia, diarrhea, rash cinzia rotondo, (93) italy cohort study pb, m 325 60.2 ± 14.2 male (42) female (58) n/a 4 days after vaccination pain, redness/swelling chills, fever, myalgia, diarrhea, headache fever yu-wei chen. (94) usa cohort study pb, m 81 70 male (60) female (40) respiratory distress, acute hemolytic anemia, shock requiring pressure support, myositis, cardiogenic shock, pancreatitis/rash 1, 5, 7 days n/a n/a patrice chevallier. (95) france prospective study pb 112 57 male (50.7) female (62.2) n/a 7 days pain, redness, swelling fever, chills, fatigue, myalgia, headache, nausea laurence chu. (96) usa white, african american, asian, american indian, native hawaiian rct second phase m 600 18-87 male (35) female (65) n/a 7 days pain, erythema, swelling, lymphadenopathy headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills coggins. (11) usa white, black, asian, hawaiian cohort study pb 206 42.4 male (30.6) female (69.4) n/a n/a soreness, pain fatigue, headache, myalgia, arthralgia, fever, chills, lymphadenopathy this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 21 archives of academic emergency medicine. 2022; 10(1): e41 table 1: severe adverse events, local and systemic side effects of mrna covid-19 vaccination first author country study type manufacturer* sample age gender (%) severe adverse event time to appearance side effects (%) local systemic efrati. (97) israel cohort study pb 333 46 male (51) female (49) n/a at least 7 days pain, redness, and swelling fever, chills, fatigue, headache, nausea, vomiting, diarrhea, muscle aches, joint aches, allergic reaction nagla a elshitany. (98) saudi arabia retrospective crosssectional pb 455 n/a male (35.8) female (64.2) n/a n/a arm pain, injection site pain, swelling, and redness whole-body pain, muscle ache, joint ache, hypersensitivity, burning sensation in the eye robert w. french. (99) multinational african american, american indian or alaska, asian, latin rct third phase pb 2260 12-25 male (51) female (49) n/a 7 days pain at the injection site, swelling, redness fatigue, headache, chills, muscle pain, joint pain, fever, diarrhea, vomiting miguel garcíagrimshaw. (40) mexico prospective observational cohort pb 704,003 36 male (74.2) female (26.8) 0.005 with no observed deaths 3 to 5 hours injection site pain headache, fatigue, muscle pain, joint pain, chills, nausea, fever, tachycardia, rhinorrhea, diarrhea, vomiting, irritability yarden golan. (100) usa african american, white, asian cohort study pb, m 50 35 female (100) none 80 days pain, redness, swelling, itching, rash around the injection site fever, chills, headache, joint pain, muscle/body aches, fatigue, nausea, diarrhea time to appearance: time from injection to the appearance of adverse events; *pb, pfizer biontech; m, moderna. rct: randomized controlled trial this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10 (1); e24 ph oto qu i z 21-year-old female with pneumothorax and massive air leak following blunt trauma; a photo quiz ahmad shirinzadeh-dastgiri1, ali saberi1, mohammad vakili2, sayed mahdi marashi3∗ 1. surgery department, iran university of medical sciences, tehran, iran. 2. surgery department, ardabil university of medical sciences, ardabil, iran. 3. patient safety research center, department of forensic medicine, school of medicine, iran university of medical sciences, tehran, iran. received: february 2022; accepted: march 2022; published online: 9 april 2022 cite this article as: shirinzadeh-dastgiri a, saberi a, vakili m, marashi sm. 21-year-old female with pneumothorax and massive air leak following blunt trauma; a photo quiz . arch acad emerg med. 2022; 10(1): e24, doi: https://doi.org/10.22037/aaem.v10i1.1513. figure 1: posterior-anterior chest x-ray (left) and axial computed tomography (ct) scan in the mediastinal and lung window (middle and right) of patient. 1. case presentation a 21-year-old female presented to the emergency department, about 20 minutes after a motorcycle accident. she was agitated and complaining of shortness of breath. her vital signs were: heart rate 110/minute, respiratory rate 32/minute, blood pressure 89/67 mmhg, temperature 36.5°c, oxygen saturation was 79% in room air, and gcs=15/15. chest auscultation revealed decreased breath sounds on the left side. other findings were tracheal deviation to the right side, distension of neck veins, decreased chest expansion and increased percussion note. therefore, the diagnosis of pneumothorax was made for the patient and a left thoracostomy tube was inserted and about 200cc of serosanguineous fluid was drained. however, massive air leak was noted and the clinical symptoms did not improve. the patient underwent chest x-ray and computed tomography (ct) scan of the chest (figure 1). what is your diagnosis? 2. diagnosis the chest x-ray showed huge pneumothorax on the left side, severe contralateral shift of the mediastinum and trachea to the right, and collapsed left lung displaced rightwards (figure 1, left); axial chest ct scan in the mediastinal window showed crumpled laminated membrane, suggestive for collapsed membrane of ruptured hydatid cyst following complete detachment into the pleural cavity (figure 2; serpent sign; red arrows). 3. case fate laboratory tests revealed white blood cell count of 10800/µl, haemoglobin of 11 g/dl, and platelet count of 318000/µl. no further laboratory tests, including enzyme-linked immunosorbent assay (elisa) for the detection of echinococcus granulosus, were requested due to the patient’s emergency status. an emergency thoracotomy was performed, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. shirinzadeh-dastgiri et al. 2 figure 2: axial computed tomography (ct) scan in the mediastinal window of patient, showing crumpled laminated membrane (red arrows). figure 3: intra-operative images of complete detachment of hydatid cyst into the pleural cavity which showed complete detachment of hydatid cyst into the pleural cavity (figure 3). after removing the cyst, washing of the pleural cavity with isotonic saline was performed, fibrotic lung tissue was removed, capitonnage was done, and a thoracostomy tube was inserted. the patient was discharged on day 5 of hospital admission with albendazole 800 mg/day for 3 months. the patient was doing well on follow-up 4 months later. her physical examinations were normal. the patient was recommended for chest x-ray, but she refused. 4. discussion hydatic disease is a zoonosis disease caused by echinococcus genus of tapeworm. the primary and intermediate hosts are carnivores and herbivores, respectively. humans are accidentally infected after ingestion of comestibles contaminated with ova of the parasite (1). cyst consists of the outer pericyst, the middle-laminated membrane, and the inner germinal layer, where the larval stage of the parasite is spent (2). the most common site of infection in adolescence and childhood are the liver and lungs, respectively (3, 4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10 (1); e24 patients with pulmonary hydatid cyst usually present with nonspecific symptoms including chest pain, cough, dyspnea, or fever. cyst rupture can occur spontaneously or after chest trauma. cyst rupture into the tracheobronchial tree may cause hypersensitivity reactions, varying from fever or rash to life-threatening anaphylaxis. it may also become complicated by pneumothorax (simple or tension), bronchopleural fistula, pulmonary collapse, or pleural empyema. tension pneumothorax is a relatively rare condition, with a prevalence of 1.3% (1, 4). the main treatment of a ruptured pulmonary hydatid cyst is surgery. the goal of surgery is to remove all the cysts, to prevent recurrence. the most appropriate surgical procedure is the one in which the cyst membrane is removed, bronchial openings are closed, and capitonnage is performed. decortication, segmentectomy, or lobectomy may be required in complicated cases. extensive washing with hypertonic saline may prevent pleural hydatidosis during surgery. albendazole is given as a complementary treatment after surgery (4). the classical imaging findings of hydatid cyst are welldescribed and generally, they are incidentally found in radiologic investigations; hence, imaging plays an important role in the diagnosis of complications. in cases of completely ruptured pulmonary hydatid cysts, connection with the bronchus signs, such as waterlily sign, rising sun sign, cumbo sign, dry cyst sign, and serpent sign may be seen (5). after perforation of the endocyst and expectoration of its internal fluid, membranes will collapse within the cyst and present with serpent sign (5). 5. conclusion: ruptured hydatid cyst has to be considered as a possible cause of pneumothorax with an associated pleural effusion in patients coming from endemic areas. 6. declarations 6.1. acknowledgements none. 6.2. conflict of interest none. 6.3. funding and support none. 6.4. authors’ contributions the authors meet the four criteria for authorship based on the recommendations of the international committee of medical journal editors (icmje). references 1. shirinzadeh a, hadadan a, vaziribozorg s. hydatid cyst of the lung in pregnancy: a rare case presentation. chinese j med res. 2020;3(1):1-3. 2. acharya s, ghimire b, khanal n. spontaneous rupture of isolated splenic hydatid cyst without acute abdomen: a case report. clin case rep. 2019;7(11):2064-7. 3. lakis m, hanna e, noujaim mg, saad ga. traumatic rupture of a solitary splenic hydatid cyst: a case report. trauma case rep. 2015;1(1-2):1-3. 4. locicero j, feins rh, colson yl, rocco g. shields’ general thoracic surgery [electronic resource] / [edited by] joseph locicero iii, richard h. feins, yolonda l. colson, gaetano rocco. 8th ed. philadelphia: wolters kluwer; 2019. 5. durhan g, tan aa, düzgün sa, akkaya s, arıyürek om. radiological manifestations of thoracic hydatid cysts: pulmonary and extrapulmonary findings. insights imaging. 2020;11(1):116. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem case presentation diagnosis case fate discussion conclusion: declarations references emergency. 2018; 6 (1): e60 le t t e r to ed i to r regression to middle effect may threaten validity of triage scales; a letter to editor amir mirhaghi1∗, mohsen ebrahimi2 1. nursing and midwifery care research center, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: september 2018; accepted: october 2018; published online: 18 november 2018 cite this article as: regression to middle effect may threaten validity of triage scales; a letter to editor. emergency. 2018; 6(1): e60. dear editor; triage is sorting patients based on acuity in order to manage care in the emergency department (ed) (1). medical institutes are trying to develop triage scales compatible with their own culture of care. a triage scale must be precise and comprehensive enough to guide triage nurses and eliminate uncertainty. it is vital to address the potential pitfalls of the new triage scales to enhance their reliability and validity. performing a validation study in other institutes provides a great opportunity for medical institutes to learn from each other. one of the newly described triage scales is the korean triage and acuity scale (ktas) in south korea (2). it has been implemented since 2015 and is a five-level system that classifies patients using a combination of variables, including vital signs and chief complaints. triage nurses are likely to triage more conservatively when applying ambiguous triage scales. they try to avoid taking risks as much as possible in clinically ambiguous situations, therefore choosing the mid-point of likert scale to mitigate any unfavorable consequences (middle effect). their error remains as low as possible when they choose triage level 3. triage level 3 is a safe category because it fits a significant portion of incoming patients and it differs only one level from triage level 2 or 4 in case of wrong selection. a recent paper on the validity of ktas showed that regression to middle effect may occur (2). almost six percent of the intensive care unit (icu) patients were assigned to triage level 4 and 5 (2). even if the fairly high proportion of the icu patients (30.69%) being allocated to level 3 can be overlooked, triage nurses categorizing patients who will be admitted to icu in level 4 or 5 is not tolerable (2). ∗corresponding author: amir mirhaghi; department of medical-surgical nursing, school of nursing and midwifery, doktorha crossroad, mashhad, razavi khorasan, iran. postcode: 9137913199 tel: 0098 51 38591511 fax: 0098 51 38539775 email: mirhaghi@mail.com therefore, it has to be said that 6% of the icu patients suffer from under-triage in this subgroup, which deserves further analysis. almost 59% percent of the general ward (gw ) patients were assigned to triage level 3. this implies that triage nurses have mostly assigned gw patients to the triage level 3, which is the most appropriate triage level for patients who need admission to gws. choosing level 3 is the most compatible with patients’ acuity in gws. almost 58% of discharged (dc) patients from the ed were assigned to the triage level 3, while 35% were placed in level 4 and 5. this shows that a large proportion of dc patients were assigned to level 3, implying that the ktas is not sensitive enough to assign low-risk patients to level 4 or 5. overall, a high proportion of level 3 patients in all three subgroups shows that triage nurses had a great tendency to assign patients to level 3, implying that regression to the middle effect took place. regression to the midpoint of a 5-point scale is reported in literature too (3). it is safe for nurses to regress to the middle in case of uncertainty. kim et al. also showed that 41.6% of patients were assigned to level 3 by the ktas compared with 38.4% for the emergency severity index (esi) (4). however, ktas is more effective than 3-level triage scale, more revisions are needed and further studies are recommended to improve its reliability and validity. in addition, patient influx in level 3 results in other parts of the ed remaining unused. this issue could not be tolerated in the ed because all ed resources must be consumed conscientiously as much as possible to reduce overcrowding. 1. appendix 1.1. acknowledgements none. 1.2. author’s contribution all authors met the four criteria for authorship contribution based on the recommendations of the international comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. mirhaghi et al. 2 mittee of medical journal editors. authors’ orcids amir mirhaghi: 0000-0002-4482-1156 mohsen ebrahimi: 0000-0003-2168-8476 1.3. conflict of interest none. 1.4. funding and support none. references 1. mirhaghi a, ebrahimi m. the australasian triage scale level 5 criteria may need to be revised. emergency. 2017;5(1):e51. 2. kwon h, kim yj, jo yh, lee jh, lee jh, kim j, et al. the korean triage and acuity scale: associations with admission, disposition, mortality and length of stay in the emergency department. international journal for quality in health care. 2018:mzy184-mzy. 3. kulas jt, stachowski aa. middle category endorsement in odd-numbered likert response scales: associated item characteristics, cognitive demands, and preferred meanings. journal of research in personality. 2009;43(3):489-93. 4. kim jh, kim jw, kim sy, hong dy, park so, baek kj, et al. validation of the korean triage and acuity scale compare to triage by emergency severity index for emergency adult patient: preliminary study in a tertiary hospital emergency medical center. journal of the korean society of emergency medicine. 2016;27(5):436-41. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 147 emergency (2014); 2 (3): 147-149 photo quiz worsened dysrhythmia after chemical cardioversion with digoxin; a case of malpractice behrooz hashemi1, mehdi pishgahi2, marzieh maleki1* 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of cardiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran figure 1  figure 2  cite this article as: kashani p, mirbaha s. confusing hypoxia in a 21-year-old intubated multiple trauma patient. emergency. 2014;2 (3): 147-9. case presentation:1 the patient was a 23-year-old man referred to the emergency department (ed) with the chief complaint of palpitation. the patient experienced dizziness, cold sweating, and lightheadedness after getting up which started spontaneously. he had four episodes of the same problems in seven months ago that felt better after taking 10 mg propranolol. however, in the current episode his problem was not solved by the same medication. he had no history of smoking, substance abuse, medication use, congenital heart disease, syncope, previous surgery, chest trauma, or any other known medical problems. as well, he had no any positive history of the same problems in his family. the patients’ onarrival vital signs were as follow: systolic blood pressure (sbp): 90 mmhg, pulse rate (pr): *corresponding author: sahar mirbaha; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. mobile phone: +989121549405; phone/fax: +982122721155. email: mirsa317@yahoo.com received: 1 april 2014; accepted: 9 april 2014 150/minute, respiratory rate (rr): 14/minute, oral temperature: 37◦c, oxygen saturation 96% with nasal cannula and 100% oxygen, glasgow coma scale (gcs) 15/15. he was not experienced any other concomitant problems such as ischemic chest discomfort, shortness of breathing, or sign of circulatory shock such as paleness, mottling, etc. on general physical examination the patients’ lung and heart sounds, four limbs pulses, and capillary refile were normal. as well, focused neurological and abdominal examinations did not have any positive finding. the patient underwent close cardiac, vital sign monitoring and electrocardiography (ecg). figure 1 shows the on-arrival patients’ ecg. atrial fibrillation (af) was diagnosed by the corresponding physician and digoxin (!?) prescribed that led to severe lethargy, weakness, sweating, and bradycardia. figure 2 shows the post mediation ecg of patient. what is your diagnosis? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 148 kashani, mirbaha diagnosis: wolff-parkinson-white (wpw) syndrome + atrial fibrillation (af) case fate: the patient was admitted to ccu and after administration of procainamide, his symptoms revealed (figure 3) and he was sent for catheter ablation. discussion: according to american heart association (aha) 2010 guideline for cardiopulmonary resuscitation (cpr), if the patient who manifested by tachycardia is presented with sever signs and symptoms including ischemic chest discomfort, acute heart failure, acute altered mental status, sustain hypotension or other signs of shock, considered as unstable case and needs immediate cardioversion. however, in other symptomatic stable ones the subject presented with irregular wide complex tachycardia, then avoiding atrioventricular (av) nodal blocking agent is crucial. these agents such as β-adrenergic blockers, calcium channel blockers, and digitalis (summarized as bcd drugs) will not be effective, cannot block the conduction over the accessory pathway, and may even enhance conduction in hypotension or other dangerous outcomes such as ventricular fibrillation (vf) and cardiac arrest. consequently, these drugs are contraindicated in such situations. lidocaine is not useful for this purpose and may rarely exacerbate the conduction. intravenous procainamide is the treatment of choice and amiodarone may be a favorable second option in spite of some opposite literatures. patients, who are hemodynamically unstable, clearly require electrical cardioversion following current instructions (1-3). wolff-parkinson-white (wpw) syndrome is used for pre-excitation on ecg accompanied by paroxysmal tachycardia that may be conducted antegrade over the normal av system or retrograde through the accessory pathway (ap). antegrade type is characterized by normal and narrow qrs complexes, regular rhythm, ventricular rate of 150-250 beats/minutes, and sudden onset and abrupt termination. the classic electrocardiographic presentation of wpw syndrome consists of short pr interval, slurred and thickened initial upstroke of the qrs complex which is termed as delta wave, relatively normal-narrow terminal qrs defluxion which sometimes referred as the main qrs defluxion, slight widening of the qrs defluxion, and secondary st segment and t wave changes (4, 5). although the incidence of dysrhythmias in wpw cases is rare, approximately 80% of dysrhythmias are av reentrant tachycardia, 15-30% atrial fibrillation (af), and 5% atrial flutter. af is considered as an emergent situation when rapid antegrade conduction over an ap occurs in wpw syndrome. clues in the ecg that may help suggesting wpw+af include rhythm irregularity, a rapid ventricular response (often with r-r intervals approaching 300 beats/minutes), wide, and bizarre qrs complexes (6, 7). szumowski et al. found that age, gender, and the history of syncope are independent risk factors of af in patients with wpw syndrome and also mentioned that antegrade conduction via ap has a major importance in the development of af (8). hamada et al. mentioned that there are two mechanisms of paroxysmal af in patients with wpw syndrome: one mechanism is reversible and ap-dependent atrial vulnerability, and the other one is intrinsic and ap-independent atrial vulnerability (9). during af developing, the custom rate-limiting impression of the av node will be bypassed, and the consecutive excessive ventricular rates (even 200240 beats/minutes) may lead to disastrous consequences such as ventricular fibrillation (vf), syncope, and sudden death. those who have survived from vf dysrhythmia, presented a rapid pre-excited ventricular response as it was demonstrated during the induction of af in electrophysiological study (2). sudden cardiac death and other possible dangerous outcomes in patients suffer from symptomatic arrhythmias can be preventable. if they are enable to tolerate a rapid pre-excited ventricular response during af (shortest pre-excited rr interval is less than 260 ms), accessory pathway catheter ablation or administration of antiarrhythmic drugs should be considered instead of such an invasive method to prevent conduction over the accessory pathway (2, 3). it could be concluded that sometimes no cure is bet figure 3  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 149 emergency (2014); 2 (3): 147-149 ter than wrong treatment. without hurry, consultant with other colleagues and adhering to present guidelines in approach to dysrhythmias can be helpful and even lifesaving. acknowledgment: we would like to express our special thanks from emergency department staffs. conflict of interest: there was no conflict of interest. author’s contribution: all authors contributed in drafting/revising the manuscript, study concept or design, and interpretation of data. references: 1. neumar rw, otto cw, link ms, et al. part 8: adult advanced cardiovascular life support: 2010 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2010;122(18 suppl 3):s729-s67. 2. hurst jw, paulk jr ea, proctor hd, schlant rc. management of patients with atrial fibrillation. am j med. 1996;37(5):728-41. 3. simonian sm, lotfipour s, wall c, langdorf mi. challenging the superiority of amiodarone for rate control in wolff-parkinson-white and atrial fibrillation. intern emerg med. 2010;5(5):421-6. 4. kaushik m, sharma m, ganju n. wolff-parkinson-white syndrome presenting as atrial fibrillation with wide-qrs complexes. j indian acad clin med. 2003;4:152-55. 5. değirmencioğu a, karakuş g, baysal e, zencirci e, çakmak n. a rare manifestation of atrial fibrillation in the presence of wolff-parkinson-white syndrome: tachycardia-induced cardiomyopathy. turk kardiyol dern ars. 2014;42(2):178-81. 6. szumowski l, orczykowski m, derejko p, et al. predictors of the atrial fibrillation occurrence in patients with wolff-parkinson-white syndrome. kardiol pol. 2009;67(9):973-8. 7. levis j, garmel g. atrial fibrillation with wolffparkinson-white syndrome. internet j emerg med. 2008;5(1):1-3. 8. szumowski ł, walczak f, urbanek p, et al. risk factors of atrial fibrillation in patients with wolff-parkinsonwhite syndrome. kardiol pol. 2004;60(3):206-16. 9. hamada t, hiraki t, ikeda h, et al. mechanisms for atrial fibrillation in patients with wolff‐parkinson‐white syndrome. j cardiovasc electrophysiol. 2002;13(3):223-9. emergency. 2018; 6 (1): e56 br i e f re p o rt rhabdomyolysis and acute poisoning; a brief report abdolkarim pajoumand1,2, farshid fahim3,4∗, meisam akhlaghdoust5, nasim zamani1,2, zeinab amirfirooz6, mahnaz dehdehasti6 1. toxicological research center, department of clinical toxicology, loghman-hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. excellence center of clinical toxicology, iranian ministry of health, tehran, iran. 3. amir-al-momenin hospital, islamic azad university, tehran medical sciences branch, tehran, iran. 4. department of clinical toxicology, loghman-hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 5. pars advanced and minimally invasive medical manners research center, pars hospital, iran university of medical sciences, tehran, iran. 6. loghman-hakim hospital poison center, shahid beheshti university of medical sciences, tehran, iran. received: march 2018; accepted: august 2018; published online: 26 september 2018 abstract: introduction: some studies have reported creatinine phosphokinase (cpk) as a new emerging way in predicting the outcomes of poisoned patients. this study aimed to evaluate the association of serum cpk level in the first 24 hours with outcomes of poisoned patients. methods: this retrospective cross-sectional study was performed using the medical profiles of poisoned patients aged between 13 and 70 years old who were referred to the emergency department of a big referral medical toxicology center during 6 years and whose necessary data for this study was available. results: 318 patients with the mean age of 34.9±14.5 years were studied (77.1% male). the mean serum cpk level of patients was 4693.1 ± 10303.8 (35–89480) iu/l. there was no significant correlation between serum cpk level and cause of poisoning (r= 0.16; p=0.51), age (r = -0.021; p = 0.651), sex (r = 0.131; p = 0.281), seizure (r = -0.022; p = 0.193), level of consciences (r = -0.138; p = 0.167), and duration of hospital stay (r= 0.242, p = 0.437). the mean serum cpk level was significantly higher in icu admitted (p<0.0001), aki (p<0.0001), hyperkalemia (p<0.0001), hypophosphatemia (p=0.045), and hypocalcaemia (p=0.008) cases. the best cut off point of serum cpk level in predicting acute kidney injury (aki) was estimated to be 10000 iu/l (sensitivity = 83.8% and specificity = 68.8%). conclusion: it seems that cpk could be considered as a candidate tool for screening the intoxicated patients in need for icu admission and at risk for aki. keywords: poisoning; creatine kinase; rhabdomyolysis; patient outcome assessment © copyright (2018) shahid beheshti university of medical sciences cite this article as: pajoumand a, fahim f, akhlaghdoust m, zamani n, amirfirooz z, dehdehasti m. rhabdomyolysis and acute poisoning; a brief report. 2018; 6(1): e56. 1. introduction acute poisoning is a major and common cause of mortality worldwide, especially in developing and low income countries (1). based on world health organization (who) reports, poisoning is responsible for 45000 deaths per year in people younger than twenty years old (available on: http://www.who.int/violence_injury_prevention/child/injur y/world_report/poisoning_english.pdf ). developing outcome prediction tools for screening and disposition of these ∗corresponding author: farshid fahim; amir-al-momenin hospital, nazi abad, tehran, iran. email: drfahim909@gmail.com tel: 009821 5534 6262. patients is one of the interesting fields of research. some studies have reported that serum creatine phosphokinase (cpk) level may become a newly emerging way in prediction of poisoning severity and outcome (1-4). it has been shown that cpk more than 10000 iu/l in poisoned patients could be associated with more complications (3, 5). cpk increase occurs in acute muscle necrosis and rhabdomyolysis. there are some possible mechanisms for increase of serum cpk in poisoning patients (6, 7). toxic serum level of any drug, muscle necrosis following substance overdose, seizure and serotonergic and neuroleptic syndromes may be possible causes of increase in the cpk level in poisoned patients (8, 9). this study aimed to evaluate the association of serum cpk level in the first 24 hours with outcomes of poisoned patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. pajoumand et al. 2 2. methods 2.1. study design and setting this retrospective cross-sectional study was performed on medical profiles of poisoning patients who were referred to emergency department (ed) of loghman hakim educational hospital, tehran, iran, between july 2011 and july 2017. loghman hakim hospital is a big referral toxicology center in the middle east. this study was approved by research ethics committee of shahid beheshti university of medical sciences and health services. 2.2. participants using census sampling, patients who were at least 13 years old and were referred to the mentioned ed and whose necessary data for this study was available (e.g.: serum cpk level of the first 24 hours of admission) were evaluated. patients with recent trauma, myocardial infarction (mi), cerebrovascular accident (cva), cardiopulmonary resuscitation (cpr) or surgery in the past 6 months, pregnancy or lactation, renal or hepatic diseases, and history of substance or fitness drug use were excluded. creatinine ≥ 1.8 mg/dl was considered as acute kidney injury (aki). 2.3. data gathering data gathering was performed using a checklist that consisted of demographic variables, consciousness level based on glasgow coma scale (gcs), history of hematuria and seizure, urinary output, serum cpk level, blood urea nitrogen (bun), creatinine level in the first 24 hours of admission, and outcomes (disposition, need for dialysis, acute kidney injury (aki), mortality, need for intubation and need for icu admission). a trained toxicology resident was responsible for gathering data from the patients’ profiles. 2.4. statistical analysis data were analyzed using ibm spss statistical software (chicago, usa) version 22 and ttest and chi square tests. p< 0.05 was considered significant. findings were presented using mean ± standard deviation or frequency and percentage. chi square, fisher’s exact, and student t tests were used for comparisons. area under the receiver operating characteristic (roc) curve was used for estimating the best cutoff point of serum cpk in predicting the occurrence of aki. 3. results: 3.1. baseline characteristics 318 patients with the mean age of 34.9±14.5 (13-85) years were studied (77.1% male). baseline characteristics of partictable 1: baseline characteristics of studied patients variable values sex female 72 (22.9) male 243 (77.1) age group (year) < 18 19 (6.0) 18 35 163 (51.4) 3560 102 (32.2) ≥60 33 (10.4) seizure yes 51 (18.7) no 222 (81.3) hematuria yes 2 (0.8) no 260 (99.2) gcs mild (1415) 56 (21.0) moderate (913) 102 (38.4 ) severe (38) 105 (39.6 ) vital signs systolic blood pressure (mmhg) 107.67 ± 21.50 pulse rate (/minute) 97 ± 26 respiration rate (/minute) 19 ± 4 oxygen saturation (%) 88.6 ± 12.3 urinary output (ml) 1s t day 1856.9 ± 1533.9 2n d day 2832.2 ± 2462.1 3r d day 2941.4 ± 1768.7 4t h day 3316.4 ± 2009.6 creatine phosphokinase (iu/l) <1000 150 (50.5) 10005000 74 (24.9) 500010000 36 (12.1) 10000-15000 12(4.0) 15000-20000 6 (2.4) >20000 19 (6.4) data are presented as mean ± standard deviation or number (%). there is missing data in some variables. table 2: causes of poisoning in the studied patients cause number (%) neuropsychiatric drugs 135 (42.4) acetaminophen 70 (22.1) alcohol 63 (19.8) opium 29 (9.1) carbone monoxide 7 (2.2) other 14 (4.4) ipants are shown in table 1. the most important cause of poisoning were benzodiazepines (24.6%) and acetaminophen (22.1%), respectively (table 2). mean serum blood urea nitrogen (bun) and creatinine levels of the studied patients were 52.89 ± 46.1 mg/dl and 1.7 ± 1.2 mg/dl, respectively. patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e56 figure 1: area under the receiver operating characteristic (roc) curve of serum creatine phosphokinase (cpk) level of poisoned patients on the first day in predicting acute kidney injury (p< 0.0001). were hospitalized for 12.74 ± 12.05 (1-72) days on average. the mean serum cpk level of studied patients was 4693.1 ± 10303.8 (35–89480) iu/l. there was no significant correlation between serum cpk level and cause of poisoning (r= 0.16; p=0.51), age (r = -0.021; p = 0.651), sex (r = 0.131; p = 0.281), seizure (r = -0.022; p = 0.193), level of consciences (r = -0.138; p = 0.167), and duration of hospital stay (r= 0.242, p = 0.437). 3.2. outcomes 37 (11.6%) cases were admitted to intensive care unit (icu), 83 (26.1%) died, and 198 (62.3%) were discharged from hospital. aki was developed in 79 (26.5%) cases out of which 14 (17.7%) needed dialysis. table 3 compares the mean serum cpk level of patients based on the studied outcomes. the mean serum cpk level was significantly higher in icu admitted (p<0.0001), aki (p<0.0001), hyperkalemia (p<0.0001), hypophosphatemia (p=0.045), and hypocalcaemia (p=0.008) cases. figure 1 shows the area under the roc curve of first day serum cpk level in predicting aki (auc= 0.752, 95%ci: 0.688-0.815; p< 0.0001). the best cut off point of serum cpk level in this regard was estimated to be 10000 iu/l based on the roc curve analysis (sensitivity = 83.8% and specificity = 68.8%). 4. discussion based on the results of the present study, there was a significant correlation between serum cpk level of poisoned patients and need for icu admission and aki development. the best cpk cut off point in predicting aki was 10000 iu/l. there was no significant correlation between serum cpk level and age, sex, level of conciseness, seizure, need for intubation, duration of hospital stay, and mortality. some of the patients that survive poisoning face mortality due to other side effects. rhabdomyolysis and its side effects including aki should be counted as common complications in these patients. if the definition of rhabdomyolysis is considered cpk level over 1000 iu/l, the prevalence of rhabdomyolysis in the patients studied in the present research will be about 50% and this emphasizes the necessity of paying attention to this matter. mild and moderate rhabdomyolysis by itself is a curable and self-limiting problem but there is controversy regarding the level of cpk that is associated with nephrotoxicity and kidney failure. this level was estimated at 15000 iu/l and higher in patients with traumatic rhabdomyolysis following bam earthquake (10-12). it seems that the cause of rhabdomyolysis affects the toxic level of this enzyme. what can be concluded from the findings of the present study is that poisoned patients with serum level of 10000 iu/l and higher are at a significant risk of nephrotoxicity and aki due to it. eizadi et al. (2012) study showed that higher levels of serum cpk level correlated with a higher risk of developing complications, increased need for dialysis and mortality (13). our findings were similar regarding the increasing risk of complication development such as aki but we had different findings regarding the correlation of serum cpk levels and need for dialysis and mortality. dadpour et al. (2017) showed that, about 80% of patients with serum cpk level > 10000 iu/l, were in need of dialysis (14). in the present study, there was no significant correlation between cpk level and need for dialysis. only 22.2% of cases in need of dialysis had cpk > 10000 iu/l in this study. nevertheless, it should be noted that rhabdomyolysis is not the sole cause of aki in poisoning patients and unlike traumatic rhabdomyolysis cases in which cpk nephrotoxicity could be considered the cause of aki with higher confidence, here more caution should be taken while interpreting the findings. it seems that when facing this type of patients, screening cases with a higher level of muscular enzymes, as well as considering other conditions, is a wise thing to do for referring them to more advanced centers with better treatment equipment. 5. limitations the limitation of this study was performing it in a retrospective manner and having missing data. 6. conclusion based on the results of the present study, there was a significant correlation between serum cpk level of poisoned pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. pajoumand et al. 4 table 3: outcomes of studied patients and its relation with serum creatine phosphokinase (cpk) levels in the first 24 hours outcome number (%) cpk level p value treated and discharged yes 196 (61.6) 4296.8±9240.5 0.323 no 122 (38.4) 5636.4±10288.3 intubation yes 98 (30.8) 5385.8±9719.9 0.216 no 193 (66.2) 3975.7±8369.8 icu admission yes 37 (11.6) 21519.9±17582.8 <0.0001 no 281 (88.4) 2246.9±3798.9 acute kidney injury yes 76 (25.9) 11731.6±15406.2 <0.0001 no 217 (74.1) 2222.9±4274.5 dialysis yes 29 (9.1) 7968.1±12763.4 0.062 no 289 (90.9) 4338.2±9202.8 mortality yes 83 (26.1) 4524.9±9168.0 0.873 no 235 (73.9) 4732.5±9798.8 hyperkalemia yes 76 (23.9) 8930.3±14716.6 <0.0001 no 242 (76.1) 1796.7±5782.9 hyperphosphatemia yes 31 (27.4) 8663.2±13855.8 0.045 no 82 (72.6) 4036.7±9243.1 hypocalcemia yes 69 (56.6) 8170.3±12647.8 0.008 no 53 (43.4) 2797.1±7855.1 tients and need for icu admission and aki development. the best cpk cut off point in predicting the aki was 10000 iu/l. there was no significant correlation between serum cpk level and age, sex, level of conciseness, seizure, need for intubation, duration of hospital stay, and mortality. 7. appendix 7.1. acknowledgements the authors would like to thank all those who have helped in this research. 7.2. author contribution none. abdolkarim pajoumand: 0000-0002-5741-455x farshid fahim: 0000-0002-5064-1303 meisam akhlaghdoust: 0000-0003-0484-9098 nasim zamani: 0000-0002-2091-0197 zeinab amirfirooz: 0000-0002-7810-9415 mahnaz dehdehasti: 0000-0002-4770-3075 7.3. conflict of interest the authors declare that there is no conflict of interest. 7.4. funding none. references 1. asadi r, afshari r. ten-year disease burden of acute poisonings in northeast iran and estimations for national rates. human & experimental toxicology. 2016;35(7):74759. 2. stewart ij, faulk ti, sosnov ja, clemens ms, elterman j, ross jd, et al. rhabdomyolysis among critically ill combat casualties: associations with acute kidney injury and mortality. journal of trauma and acute care surgery. 2016;80(3):492-8. 3. babak k, mohammad a, mazaher g, samaneh a, fatemeh t. clinical and laboratory findings of rhabdomyolysis in opioid overdose patients in the intensive care unit of a poisoning center in 2014 in iran. epidemiology and health. 2017;39. 4. mural r, bajaj g, mammen d. study of level of total serum creatine phosphokinase as prognostic indicator in acute organophosphorus poisoning: a prospective study. international journal of contemporary medical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e56 research. 2017;4(2):578-82. 5. bhattacharyya k, phaujdar s, sarkar r, mullick os. serum creatine phosphokinase: a probable marker of severity in organophosphorus poisoning. toxicology international. 2011;18(2):117. 6. deighan cj, wong km, mclaughlin kj, harden p. rhabdomyolysis and acute renal failure resulting from alcohol and drug abuse. qjm : monthly journal of the association of physicians. 2000;93(1):29-33. 7. hoaken pn, stewart sh. drugs of abuse and the elicitation of human aggressive behavior. addictive behaviors. 2003;28(9):1533-54. 8. zutt r, van der kooi a, linthorst g, wanders r, de visser m. rhabdomyolysis: review of the literature. neuromuscular disorders. 2014;24(8):651-9. 9. kamal f, snook l, saikumar jh. rhabdomyolysisassociated acute kidney injury with normal creatine phosphokinase. the american journal of the medical sciences. 2018;355(1):84-7. 10. safari s, yousefifard m, hashemi b, baratloo a, forouzanfar mm, rahmati f, et al. the value of serum creatine kinase in predicting the risk of rhabdomyolysisinduced acute kidney injury: a systematic review and meta-analysis. clinical and experimental nephrology. 2016;20(2):153-61. 11. hosseini m, safari s, sharifi a, amini m, farokhi fr, sanadgol h, et al. wide spectrum of traumatic rhabdomyolysis in earthquake victims. acta medica iranica. 2009;47(6):459-64. 12. hashemi b, safari s, hosseini m, yousefifard m, erfani e, baratloo a, et al. a systematic review of iranian experiences in seismo-nephrology. archives of trauma research. 2016;5(2). 13. eizadi-mood n, sabzghabaee am, gheshlaghi f, mehrzad f, fallah z. admission creatine phosphokinase in acute poisoning: is it a predictive factor for the treatment outcome. j pakistan med assoc. 2012;62(3 suppl 2):s67-70. 14. dadpour b, tajoddini s, shaarbaf eidgahi e, shokouhizadeh m, shafahi a. role of serum creatinine phosphokinase in outcome prediction of intoxicated patients; a brief report. emergency. 2017;5(1):e63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion limitations conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e28 https://doi.org/10.22037/aaem.v9i1.1167 le t t e r to ed i to r emergency department and overcrowding during covid-19 outbreak; a letter to editor jean-baptiste bouillon-minois1,2∗, julien raconnat1, maelys clinchamps3, jeannot schmidt1,2, frédéric dutheil2,3 1. emergency medicine, chu clermont-ferrand, université clermont auvergne, f–63000 clermont–ferrand, france. 2. cnrs, lapsco, physiological and psychosocial stress, f–63000 clermont–ferrand, france. 3. preventive and occupational medicine, chu clermont-ferrand, f-63000 clermont-ferrand, france. received: january 2021; accepted: february 2021; published online: 25 march 2021 cite this article as: bouillon-minois j-b, raconnat j, clinchamps m, schmidt j, dutheil f. emergency department and overcrowding during covid-19 outbreak; a letter to editor. arch acad emerg med. 2021; 9(1): e28. dear editor, emergency physicians (eps) work under extreme stress conditions (1). overcrowding – defined as hospital beds not being available for several patients who need one – has been a significant public health problem for more than a decade and is the consequence of the increase in health care demand and the decrease in bed spaces and number of staff (2). these parameters increase stress at work, which leads eps to experience significant stress consequences, a feeling of diminished skills, and loss of time control (3). many studies are interested in the overcrowding problem, like a recent study by tangkulpanich et al. who found the predictive factors of revisiting in 48 hours (4). since the end of 2019, because of covid-19, people were required to stay at home to prevent the spread of covid-19 and the overflow of emergency and intensive care units. but in some places, there was no overflow, and a massive decrease, up to 50%, was observed in admission rate (5). in the rural area of puy-de-dôme – 653 742 inhabitants with a density of 82 inhabitants/km2 – only 335 patients had a positive test, with 30 deaths by july 1s t , 2020. in the emergency department of clermont-ferrand – the principal city of puy-dedôme –, there were 57 177 admissions in 2019 – i.e., a mean of 157 per day. of those 57 177 emergency department admissions, 38 809 were discharged, and 18 368 (i.e., 50 per day) were hospitalized. but even if the hospital provided 21 851 available beds annually (60 per day), eps spent 152 days on overcrowding. ∗corresponding author: jean-baptiste bouillon-minois; university hospital of clermont-ferrand (chu), emergency department, 58 rue montalembert, 63000 clermont-ferrand, france. tel: +33 (0)6 74 36 04 23, fax: +33 (0)4 73 27 46 49, email: jbb.bouillon@gmail.com. contrary to 2019, the year 2020 offered a massive decrease in the admission rate, with a maximum of 204 beds available on april 3rd, 2020. during the french covid-19 lockdown between march 17t h and may 11t h , there were no overcrowded days (55 days). as soon as the global lockdown ended, the emergency department was overcrowded again (figure 1). moreover, despite the cooling period of lockdown with a large number of beds available and few patients needing to be admitted, the year 2020 seemed harder than 2019. indeed, 75 days out of the initial 185 days of the year (40.5%) were overcrowded in 2020, similar to 2019 with 79/185 overcrowding days (43%) during the first half of the year (table 1). if we remove the 55 days of the covid-19 lockdown, the percentage of overcrowded days rise up to about 58% in 2020. although in-hospital mortality and hospital length of stay are correlated with the size of emergency department boarding (6), the number of hospitalization beds in france decreased from 468 000 in 2003 to 408 in 2015. in the same period, the number of admissions in the emergency departments increased from 15.5 million to 21 million per year in france. furthermore, emergency departments are identified as high-risk settings for medical errors and adverse events (7), concerning up to 10% of admissions. at the same time, several complaints are growing by approximately 1% per year, which may involve a rise of complementary investigations by fear of missing a diagnosis, increasing the time spent in emergency departments, and the stress of both patients and physicians (8). interestingly, during the french covid-19 lockdown, one author reported 32% decrease in transitory ischemic attacks, 64% in unstable angina, 42% in appendicitis, and 36% in seizures. however, we demonstrated that although the number of admissions hugely decreased (nearly by half ) during the lockdown, the mean number of patients needing hospitalization during the first half of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j-b. bouillon-minois et al. 2 the year stayed similar (around 50 per day). lastly, although the lockdown was not so problematic for emergency departments, the following months were a challenging period. during the french lockdown, planned surgery and medical consultations were canceled as much as possible and every surgeon, every staff member – emergency physician or not – was prepared to fight against covid. but afterwards they wanted to reschedule the canceled surgeries and canceled meetings, and there were not more beds available for patients from emergency departments in hospitals. the months after the lockdown were tricky as the number of patients to hospitalize started to rise again, without downstream beds. 1. conclusion contrary to the common opinion, the covid-19 lockdown was not the most terrible period for eps. it even appeared that the lockdown could be considered the gold standard for patient care in emergency departments, without any problem to find a bed for those needing to be hospitalized. 2. declarations 2.1. acknowledgment to dominique romain, for her daily work. 2.2. conflicts of interest the authors of this work declare no conflict of interest. 2.3. funding support not applicable. 2.4. authors’ contributions jbbm performed the statistics and wrote the manuscript. jr created the database and performed the extraction of all data. mc created the figure and the table. js supervised the creation of the database and review the manuscript. fd wrote the manuscript and performed statistics. references 1. dutheil f, boudet g, perrier c, lac g, ouchchane l, chamoux a, et al. jobstress study: comparison of heart rate variability in emergency physicians working a 24hour shift or a 14-hour night shift—a randomized trial. int j cardiol. 2012;158(2):322-5. 2. di somma s, paladino l, vaughan l, lalle i, magrini l, magnanti m. overcrowding in emergency department: an international issue. internal and emergency medicine. 2015;10(2):171-5. 3. lindeberg si, rosvall m, choi b, canivet c, isacsson so, karasek r, et al. psychosocial working conditions and exhaustion in a working population sample of swedish middle-aged men and women. european journal of public health. 2011;21(2):190-6. 4. tangkulpanich p, yuksen c, kongchok w, jenpanitpong c. clinical predictors of emergency department revisits within 48 hours of discharge; a case control study. archives of academic emergency medicine. 2021;9(1). 5. bouillon-minois j-b, schmidt j, dutheil f. sars-cov-2 pandemic and emergency medicine: the worst is yet to come. the american journal of emergency medicine. 2020. 6. singer aj, thode jr hc, viccellio p, pines jm. the association between length of emergency department boarding and mortality. academic emergency medicine. 2011;18(12):1324-9. 7. freund y, goulet h, leblanc j, bokobza j, ray p, maignan m, et al. effect of systematic physician cross-checking on reducing adverse events in the emergency department: the charmed cluster randomized trial. jama internal medicine. 2018;178(6):812-9. 8. heath i. role of fear in overdiagnosis and overtreatment—an essay by iona heath. bmj. 2014;349. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e28 table 1: number of hospitalizations needed and beds available per day and overcrowded days during first six months of the years 2019 and 2020 variables 2019 (185 days) 2020 (185 days) p value hospitalizations/day 51.0 ± 10.8 47.0 ± 10.1 <0.001 beds available/day 59.0 ± 27.1 69.0 ± 46.6 <0.01 overcrowded (days) 79 (42.7) 75 (40.5) 0.32 data are presented as mean ± standard deviation of number (%). figure 1: overcrowding in the emergency department of clermont-ferrand between january 1s t and june 30t h 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 141 emergency 2014; 2 (3): 141-143 case report gastric perforation and phlegmon formation by foreign body ingestion albert alejandro avila alvarez1*, jose fernando parra1, diego andres buitrago2, fernando rodriguez3, atilio moreno1 1. department of emergency medicine, pontifical xavierian university, bogotá d.c, colombia 2. department of surgery, hospital universitario san ignacio, pontifical xavierian university, bogotá d.c, colombia 3. department of radiology, hospital universitario san ignacio, pontifical xavierian university, bogotá d.c, colombia abstract this is a case report of foreign body ingestion in a suicide attempt resulting in gastric perforation and phlegmon formation during a subsequent 6 month period that eventually required surgical intervention. the patient had a prolonged course because she did not report a history of foreign body ingestion and the initial evaluating physicians had no suspicion about possible foreign body ingestion and may have missed important findings on physical examination. gastric perforation by a foreign object may have a slow course rather than presenting acute abdomen. the realization of a proper physical examination in the emergency department is key to an accurate diagnosis. key words: stomach; cellulitis; phlegmon; foreign body cite this article as: avila alvarez aa, parra jf, buitrago da, rodriguez f, moreno a. gastric perforation and phlegmon formation by foreign body ingestion. emergency. 2014;2(3):141-3. introduction: 1 atients with foreign bodies in their gastrointestinal tract are a common occurrence in emergency medicine (1, 2). the majority of these foreign bodies transit through the gastrointestinal system without any complication, and have more than a 90% chance of passing into the small intestine if they get to the stomach (1-3). it is very likely that things the size of coins would pass through the small intestine without any complication; however, objects larger than 2 cm in diameter are unlikely to pass through the pylorus, and objects witch are more than 6 cm in length are often caught in the pylorus easily. in the end, only 1% of ingested foreign objects manage to pierce the gastrointestinal tract (2). case report: we present a case of a 21-year-old female who, in the month prior to admission to our institution, had been treated multiple times in emergency departments at various hospitals referring epigastric abdominal pain and constipation. the treatment she received was based on the resolution of constipation, antacids and dietary recommendations. the patient was admitted to our emergency department after 1-month of upper quad-rant abdominal pain radiating to the left upper quad-rant, additionally she cited a weight loss of 5 kg in the last month. her symptoms had become more aggravated two days prior to admission with unquantified fever, chills and *corresponding author: albert alejandro avila alvarez; department of emergency medicine, pontificia universidad javeriana, bogotá d.c., colombia, carrera 7 no. 40-62 tel/fax: (571) 3208320; email: alejandroavila2010@gmail.com received: june 2014; accepted: june 2014 night sweats. she had no history of previous peptic ulcer disease or surgical procedures. a review of the family history revealed no significant disease. a physical examination revealed vital sings with a heart rate of 102 beats per minute, respiratory rate 16 breaths per minute, temperature of 37°c, blood pressure of 110/56mmhg, the abdomen was distended, the percussion was tympanic, the bowel sounds were de-creased. additionally we found a painful, not well limited, mass adhered to deep planes in the abdominal palpation without peritoneal irritation or other alterations. a work-up started with blood chemistry, cbc, and we requested a ct of the abdomen due to clinical examination findings. the preclinical showed no elevation of acute phase reactants and no electrolyte disturbance, the ct scan evidenced an irregular, small collection in the gastric antrum and behind the left rectus muscle of approximately 30x11x16mm, which was associated with increased density of the surrounding fat. inside this area, the end of a tubular, hypodense structure (compatible with foreign body) was visible coming out from the gastric lumen through the wall, which was perforated (figure 1 and 2). the findings on ct were dis-cussed with the patient who was questioned again for further information to determine the origin of the foreign body. the patient agreed to tell the truth. she ad-mitted having a major depressive episode 6 months ago and attempted of suicide. she had ingested a plastic stick from a candy (chocmelo ®) (figure 3). she was referred to general surgery service who decided to take the patient immediately to the surgery room and performed an exploratory laparotomy. during the procep mailto:alejandroavila2010@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 142 avila alvarez et al dure, they found a perforation in the anterior wall of the stomach between the gastric body and the antrum, it was associated with a great inflammatory plas-tron generating a gastrocolic ligament edema. they therefore decided to perform a subtotal gastrectomy removing 50% of the stomach and then roux-y reconstruction. histopathological examination revealed severe inflammation, with abscess formation and severe submucosal edema. discussion: perforation of the gastrointestinal tract by purposeful ingestion of foreign bodies in adults is usually secondary to accidental ingestion which is often caused by foreign bodies included in meals (1, 3). predisposing factors include prostheses, patients with a history of psychosis or psychiatric disease, alcohol abuse and being in prison. objects that are frequently ingested are the teeth, toothbrushes and foreign bodies from the diet such as fish and chicken bones. the most commonly affected sites are the distal ileum, sigmoid colon or rectum (1, 2). patients with perforation of the stomach, duodenum, or large intestine, usually ingest larger objects (2). the clinical presentation of gastric perforation by a foreign body tends to be hidden, with unspecific gastrointestinal symptoms such as chronic abdominal distension, decreased appetite, and epigastric mass sensation, usually with normal laboratory results (1, 3). the patient in this case had multiple visits to the doctor after the foreign body ingestion, and was treated for figure 1: enhanced ct of the superior abdomen in venous phase, which demonstrates in sagittal (a) and coronal planes (b) the tubular air filled foreign body (white arrow) penetrating the gastric wall (arrow heads), associated with peripheral fat stranding (curved arrow).  figure 2: enhanced ct of the superior abdomen in venous phase, which demonstrates in sagittal (a) and axial planes (b) the tip of the tubular air filled foreign body (white arrow) in the peritoneal fat surrounded by a fluid collection with an enhancing wall (arrow heads).  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 143 emergency 2014; 2 (3): 141-143 peptic ulcer disease and constipation. important to highlight is, the patient did not mention any foreign body ingestion until she was confronted with the scan results. finally, we made a search in the literature and we surprisingly found that when there is gastric or duodenal perforation by a foreign object the clinical findings are similar to our case, for instance in the vast majority there was a slow course and latency period before presenting with the acute phase. a common finding besides gastric perforation was an inflammatory plastron or abscess, and was always treated with laparotomy and in some limited cases with minimal laparotomy plus abscess drainage and suture of the primary defect in the stomach and in two cases a patch of omentum was used (4, 5). in the case of our patient a subtotal gastrectomy of 50% with roux-y reconstruction was performed due to severe transmural inflammation, accompanied by multiple abscesses and a severe submucosal edema. the patient had a favorable outcome without any complications and has gained some of the lost weight. after treatment, the patient was discharged home on the 5th day after admission. gastric perforation by a foreign object may have a slow course rather than presenting acute abdomen. gastric perforation by a foreign object the picture may have a slow course rather than presenting acute abdomen. the realization of a proper physical examination in the emergency department is key to an accurate diagnosis. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of hospital universitario san ignacio hospitals in bogotá d.c, colombia. conflict of interest: authors declared no conflict of interest. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. rao v, sarkar r, turner r, wedgwood k. unusual presentation of gastric perforation by foreign body: a case report. case rep surg. 2011;2011:1-2. 2. goh bk, chow pk, quah h-m, et al. perforation of the gastrointestinal tract secondary to ingestion of foreign bodies. world j surg. 2006;30(3):372-7. 3. lam py, marks m, fink a, oliver m, woodward a. delayed presentation of an ingested foreign body causing gastric perforation. j paediatr child health. 2001;37(3):303-4. 4. mehran a, podkameni d, rosenthal r, szomstein s. gastric perforation secondary to ingestion of a sharp foreign body. jsls. 2005;9(1):91-3. 5. steenvoorde p, moues cm, viersma jh. gastric perforation due to the ingestion of a hollow toothpick: report of a case. surg today. 2002;32(8):731-3. figure 3: type of candy whose stick was reportedly swallowed.  archives of academic emergency medicine. 2019; 7 (1): e14 br i e f re p o rt association of lymphopenia with short term outcomes of sepsis patients; a brief report hojat sheikh motahar vahedi1,2, aida bagheri2, amirhosein jahanshir1,2, javad seyedhosseini1,2, elnaz vahidi1,2∗ 1. prehospital research center, tehran university of medical sciences, tehran, iran. 2. department of emergency medicine, shariati hospital, tehran university of medical sciences, tehran, iran. received: october 2018; accepted: december 2018; published online: 20 january 2019 abstract: introduction: studies have claimed that low lymphocyte count is independently correlated with 28-day survival of sepsis patients. therefore, this study aimed to evaluate the value of lymphopenia in predicting the short-term outcome of sepsis patients. methods: this cross-sectional study was performed on sepsis patients referred to the emergency department during an 8-month period and relationship of lymphopenia with 28-day mortality and probability of septic shock and readmission due to sepsis was assessed. results: 124 cases with the mean age of 66.12 ± 15.82 (21-90) years were studied (54.8% male). 81 (65.3%) cases had lymphopenia (59.3% male). lymphopenic patients had a significantly higher mean age (p = 0.003), higher need for icu admission (p < 0.001), higher prevalence of 28-day septic shock (p < 0.001), higher 28-day mortality (p < 0.001), higher probability of readmission due to sepsis (p = 0.048), and higher sofa score (p < 0.001). during 28 days of follow up, 57 (46%) patients were expired. they had a higher prevalence of septic shock (p < 0.001) and higher sofa score (p < 0.001). multivariate analysis showed that septic shock (or=364.6; 95% ci: 26.3 to 5051.7; p = 0.001) and lymphopenia (or=19.2; 95% ci: 1.7 to 211.3; p = 0.016) were the independent predictors of 28-day mortality. conclusion: based on the findings, lymphopenia was independently associated with higher 28-day mortality and lymphopenic patients were older than the control group and had a significantly higher need for icu admission, higher probability of 28-day septic shock and readmission due to sepsis, and higher sofa score. keywords: lymphopenia; sepsis; prognosis; emergency service, hospital cite this article as: sheikh motahar vahedi h, bagheri a, jahanshir a, seyedhosseini j, vahidi e. pan vs. association of lymphopenia with short term outcomes of sepsis patients; a brief report. arch acad emerg med. 2019; 7(1): e14. 1. introduction sepsis is one of the most common causes of emergency department (ed) referral among all different ages, especially elderlies. it is reported that 571000 severe sepsis cases are annually referred to eds in the us. its mortality risk is between 20% and 50% and it is among the 10th most common reasons of mortality and morbidity in us (1-3). currently, it is believed that sepsis triggers a complicated immunologic response that impairs the balance between pro and anti-inflammatory processes. this results in an immune suppression phase leading to progressive primary and secondary infections, and high morbidity and mortality rates (7). ∗corresponding author: elnaz vahidi; department of emergency medicine, shariati hospital, tehran, iran. tel: +982184902719; email: evahidi62@yahoo.com one of the immune suppression characteristics in sepsis is apoptosis of immune cells including t-helper and cytotoxic lymphocytes, b lymphocytes and dendritic cells (8). many studies have shown that lymphocyte count decreases in the early phase of sepsis and follows the same pattern during the first 28 days (8-13). it was reported that neutrophilia and lymphopenia were both related to bacteremia, but the latter had a higher predictive value. it is also found that both neutrophilia and lymphopenia had more prognostic value than total white blood cell (wbc) count (14). it was also claimed that low lymphocyte count independently correlates with 28-day patient survival rate in sepsis and some special types of organ failure (15). based on the above-mentioned points, this study aimed to evaluate the value of lymphopenia in predicting the shortterm outcome of sepsis patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. sheikh motahar vahedi et al. 2 table 1: comparing the characteristics of lymphopenic sepsis patients with non-lymphopenic ones variables lymphocyte count p value < 1500 (n = 81) ≥ 1500 (n = 43) sex (%) male 48 (59.3) 20 (46.5) 0.182 female 33 (40.7) 22 (51.2) age (year) 18 45 4 (4.9) 8 (18.6) 45 60 16 (19.8) 9 (20.9) 0.042 ≥ 60 61 (75.3) 26 (60.5) duration of admission (day) mean ± sd 10.90 ± 6.67 9.79 ± 5.81 0.359 need for icu admission yes 42 (51.9) 6 (14.0) <0.001 no 39 (48.1) 37 (86.0) source of infection pneumonia 50 (61.7) 23 (53.5) urinary tract 19 (23.5) 12 (27.9) soft tissue 4 (4.9) 3 (17.0) 0.914 central nervous system 1 (1.2) 1 (2.3) others 7 (8.6) 4 (9.3) sofa score mean ± sd 5.74 ± 2.58 3.90 ± 2.22 < 0.001 28-day outcome mortality 59 (88.1) 8 (11.9) < 0.001 septic shock 57 (85.1) 10 (14.9) < 0.001 readmission 20 (52.6) 18 (47.4) 0.048 data are presented as mean ± standard deviation (sd) or number (%). 2. methods 2.1. study design and setting this cross-sectional study was performed on sepsis patients referred to emergency department of shariati hospital, tehran, iran, during the first 8 months of 2017. the study method was approved by the ethics committee of tehran university of medical sciences and the code of ir.tums.medicine.rec.1395.1627 has been assigned. signed informed written consent has been obtained from all patients or their family to participate in our study. 2.2. participants sampling was performed prospectively in a continuous manner and all patients over 18 years old suspected of having sepsis who were admitted to the ed were eligible. concomitant underlying diseases affecting white blood cell (wbc) count like blood dysplasia, history of immune deficiency or being under chemotherapy, death before the 4t h day, and unwillingness to participate in our research were considered as exclusion criteria. 2.3. data gathering a predesigned checklist including the demographic information of patients as well as source of infection, sequential organ failure assessment (sofa) score, length of hospital stay, need for intensive care unit (icu) admission, lymphocyte count, and 28-day outcome was filled for all patients by a senior emergency medicine resident. peripheral blood samples were taken on the admission day and 4 days later, and complete blood count (cbc) and cell differentiation were performed. lymphopenia was defined as lymphocyte count <1500 cells/µl and lymphocyte count ≥1500 cells/µl was considered normal. this count should have remained in the same group during the first 4 days of admission, and the cases whose count changed over 4 days were excluded. 28-day mortality, 28-day readmission due to sepsis, and 28-day prevalence of septic shock were considered as outcomes. 2.4. statistical analysis spss v.22 was used for statistical analyses. descriptive statistics, including mean ± standard deviation or frequency (percentage) were used for reporting the findings. comparison of baseline characteristics between 28-day survivors and expired patients was done using unpaired t-test, mannwhitney u test, or chi-square test, as appropriate. to determine the independent effect of absolute lymphocyte count on 28-day mortality, logistic regression analysis was used. p < 0.05 was considered as level of significance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e14 table 2: comparing the characteristics of expired and survived groups variables died (n=67) survived (n=57) p-value sex male 37 (55.4) 31 (54.4) 0.553 female 30 (44.8) 26 (45.6) age (year) mean ± sd 73.10 ± 12.41 57.91 ± 15.54 0.001 source of infection (%) pneumonia 44 (65.7) 29 (50.9) urinary tract 14 (20.9) 17 (29.9) soft tissue 3 (4.5) 4 (7.1) 0.652 central nervous system 1 (1.5) 1 (1.5) others 5 (7.4) 6 (10.6) septic shock number (%) 64 (95.5) 3 (5.3) 0.001 lymphocyte count mean ± sd 991.7 ± 684.7 1923.8 ± 1167.9 median (iqr) 847.0 (784.0) 1600.0 (1011.0) 0.001 lymphopenia<1500 (%) 59 (88.1) 22 (38.6) sofa score mean ± sd 6.9 ± 2.0 2.9 ± 0.9 0.001 median (iqr) 6.0 (4.0) 3.0 (1.0) iqr: interquartile range; sd: standard deviation; sofa: sepsis related organ failure assessment. data are presented as mean ± data are presented as mean ± standard deviation (sd) or number (%). 3. results: 143 patients suspected of having sepsis were studied, 124 of whom met the inclusion criteria. the mean age of the participants was 66.12 ± 15.82 (21-90) years (54.8% male). 81 (65.3%) cases had lymphopenia (59.3% male). table 1 compares the characteristics of lymphopenic patients with others. lymphopenic patients had a significantly higher mean age (p = 0.003), higher need for icu admission (p < 0.001), higher prevalence of 28-day septic shock (p < 0.001), higher 28-day mortality (p < 0.001), higher probability of readmission due to sepsis (p = 0.048), and higher sofa score (p < 0.001). during 28 days of follow up, 57 (46%) patients were expired. table 2 compares the characteristics of dead and survived patients. the mean age of the expired patients was significantly higher (p=0.001). they had a significantly higher rate of lymphopenia (p < 0.001), higher prevalence of septic shock (p < 0.001), and higher sofa score (p < 0.001). multivariate analysis showed that septic shock (or=364.6; 95% ci: 26.3 to 5051.7; p = 0.001) and lymphopenia (or=19.2; 95% ci: 1.7 to 211.3; p = 0.016) were independent significant predictors of 28-day mortality. 4. discussion based on the findings, lymphopenia was independently associated with higher 28-day mortality and lymphopenic patients were older than the control group and had a significantly higher need for icu admission, higher probability of 28-day septic shock and readmission due to sepsis, and higher sofa score. some previous studies like those of cheadle et al., felmet et al., monserrat et al., hein et al., and inoue et al. confirmed that b and t cell lymphocyte counts had significantly reduced during the first week of diagnosis in patients who died of sepsis (8-12). in 2014, drewry et al. studied 335 adult patients with bacteremia and sepsis and reported the death of 77 cases within 28 days after admission. they showed that the median lymphocyte count on the 4th day of admission was a good independent predictor in mortality prediction (4). in 2015, chung et al. announced that severe lymphopenia was associated with elevated plasma interleukin (il)-15 levels and increased mortality during severe sepsis (1). they considered severe lymphopenia as lymphocyte count less than 0.5 ×103 cells/µl and found that it was associated with increased 28-day mortality in severe sepsis. like in our study, pneumonia and urinary tract infections were the most common sources of sepsis in the population they studied. they reported that septic shock had a higher incidence rate in the expired group. expired group had a higher sofa score compared to survivors. in 2017, li et al. performed a study on 63 patients with severe sepsis and they used the ratio of il-10 to lymphocyte count as a predictor of 28-day mortality and severity. this ratio showed moderate sensitivity and specificity (around 70%) in their study (16). expired group had significantly lower lymphocyte count than the survivors. wyllie in 2004 and chien et al. in 2012 suggested that both lymphocyte and neutrophil counts should be considered in adults with suspected bacteremia (13, 14). they showed a quantitative association bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. sheikh motahar vahedi et al. 4 tween lymphopenia and the risk of bacteremia. based on the results of the present and the mentioned study, it seems that lymphopenia could be considered as a predictor of 28-day mortality and bad outcome of sepsis patients presenting to emergency department. 5. conclusion based on the findings, lymphopenia was independently associated with higher 28-day mortality and lymphopenic patients were older than the control group and had a significantly higher need for icu admission, higher probability of 28-day septic shock and readmission due to sepsis, and higher sofa score. 6. appendix 6.1. acknowledgements the authors would like to express their special thanks to the prehospital research center for their support in conducting this study. 6.2. author contribution all the authors of this study met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. authors’ orcids hojat sheikh motahar vahedi: 0000-0002-6796-6403 amirhosein jahanshir: 0000-0002-0449-4314 javad seyedhosseini: 0000-0002-9131-9732 elnaz vahidi: 0000-0002-4580-1456 6.3. funding no funding was received for this study. 6.4. conflict of interest none declared. references 1. chung kp, chang ht, lo sc, chang ly, lin sy, cheng a, et al. severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis. shock (augusta, ga). 2015;43(6):569-75. 2. macdonald sp, williams jm, shetty a, bellomo r, finfer s, shapiro n, et al. review article: sepsis in the emergency department part 1: definitions and outcomes. emergency medicine australasia : ema. 2017;29(6):619-25. 3. mirbaha s, abushouk ai, negida a, rouhipour a, baratloo a. the effect of fluid therapy on hemodynamic and venous blood gas parameters in patients with septic shock. journal of medical physiology. 2016;1(2):55-9. 4. drewry am, samra n, skrupky lp, fuller bm, compton sm, hotchkiss rs. persistent lymphopenia after diagnosis of sepsis predicts mortality. shock (augusta, ga). 2014;42(5):383-91. 5. bloos f. clinical diagnosis of sepsis and the combined use of biomarkers and cultureand non-culture-based assays. methods in molecular biology (clifton, nj). 2015;1237:247-60. 6. baratloo a, rahmati f, rouhipour a, motamedi m, gheytanchi e, amini f, et al. correlation of blood gas parameters with central venous pressure in patients with septic shock; a pilot study. bulletin of emergency and trauma. 2014;2(2):77-81. 7. hotchkiss rs, monneret g, payen d. sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. nature reviews immunology. 2013;13(12):862-74. 8. hattori y, hattori k, suzuki t, matsuda n. recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: novel therapeutic implications and challenges. pharmacology & therapeutics. 2017;177:56-66. 9. wesche de, lomas-neira jl, perl m, chung cs, ayala a. leukocyte apoptosis and its significance in sepsis and shock. journal of leukocyte biology. 2005;78(2):325-37. 10. monserrat j, de pablo r, reyes e, diaz d, barcenilla h, zapata mr, et al. clinical relevance of the severe abnormalities of the t cell compartment in septic shock patients. critical care (london, england). 2009;13(1):r26. 11. felmet ka, hall mw, clark rs, jaffe r, carcillo ja. prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. journal of immunology (baltimore, md : 1950). 2005;174(6):3765-72. 12. venet f, davin f, guignant c, larue a, cazalis ma, darbon r, et al. early assessment of leukocyte alterations at diagnosis of septic shock. shock (augusta, ga). 2010;34(4):358-63. 13. wyllie dh, bowler icjw, peto tea. relation between lymphopenia and bacteraemia in uk adults with medical emergencies. journal of clinical pathology. 2004;57(9):950-5. 14. chien y-c, chung k-p, cheng j-s, chang h-t, yu cj. lymphopenia is associated with worse outcome in patients with severe sepsis. d57 sepsis: of mice, metabolomics, and man: american thoracic society; 2012. p. a5992-a. 15. markwart r, condotta sa, requardt rp, borken f, schuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e14 bert k, weigel c, et al. immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naive t-cells but no enduring cell-autonomous defects in t-cell function. plos one. 2014;9(12):e115094-e. 16. li x, xu z, pang x, huang y, yang b, yang y, et al. interleukin-10/lymphocyte ratio predicts mortality in severe septic patients. plos one. 2017;12(6):e0179050. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e9 https://doi.org/10.22037/aaem.v9i1.1045 le t t e r to ed i to r discrepancy in screening performances of different rapid test kits for sars-cov-2; a letter to editor phee kheng cheah1∗ darlene f. ongkili2, fatin salwani zaharuddin1, muammar iqbal hashim1, chiak vun ho3, heng gee lee4, phaik kin cheah5 1. emergency and trauma department, sabah women and children’s hospital, ministry of health, kota kinabalu, sabah, malaysia. 2. emergency and trauma department, queen elizabeth hospital, ministry of health, kota kinabalu, sabah, malaysia. 3. department of pathology, queen elizabeth hospital, ministry of health, kota kinabalu, sabah, malaysia. 4. infectious disease unit, queen elizabeth hospital, ministry of health, kota kinabalu, sabah, malaysia. 5. faculty of arts and social science, universiti tunku abdul rahman, perak, malaysia. received: november 2020; accepted: november 2020; published online: 13 december 2020 cite this article as: cheah pk, ongkili df, zaharuddin fs, hashim mi, ho cv, lee hg, cheah pk. discrepancy in screening performances of different rapid test kits for sars-cov-2; a letter to editor. arch acad emerg med. 2021; 9(1): e9. dear editor, point-of-care testing has always been an attractive modality to quickly confirm diagnosis in the emergency department (ed). this attribute is highly valuable during the current coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sarscov-2), where early diagnosis means quicker case detection and earlier isolation. rapid test kits (rtks) developed to diagnose covid-19 utilised two types of assay to detect sars-cov-2 infection(1). molecular assays detect antigen in the form of viral rna or protein on the patient’s respiratory tract, whilst serology immunoassays are used to detect igm and igg antibodies in the blood. there are many rtks available commercially, but reports on effectiveness are scarce. we share the results of our study, which evaluated three colloidal gold-based immunoassay rtks available in our centre (sabah women and children’s hospital, kota kinabalu, malaysia). we conducted an observational quantitative study in april 2020, after ethics approval was received from the medical research & ethics committee, ministry of health, malaysia (ethics approval number: nmrr-20-640-54491). the participants selected for this study were relatively well patients who were confirmed to be positive for covid-19 using reverse transcriptase polymerase chain reaction (rt-pcr) testing ∗corresponding author: phee kheng cheah; emergency and trauma department, sabah women and children’s hospital, locked bag 187, 88986 kota kinabalu, sabah, malaysia. email: pkheng1@yahoo.com, tel: +6016-8108384, orcid: https://orcid.org/0000-0002-2523-2997. on nasopharyngeal samples from contact screening. these patients were categorized based on their epidemiological link as well as if they were symptomatic or asymptomatic on their initial arrival to the ward. the three rtks available in our centre were assigned as rtk1, rtk2 and rtk3. after obtaining consent, capillary sampling was performed and applied on the rtk. the result was read at 15 minutes as per kit’s instructions and recorded on the data collection form. the researchers then proceeded to complete the patient characteristics section and sampling details section of the data collection form. patient characteristics included age, gender, comorbidities, date of admission, and patient presentation. sampling details included date and result of rt-pcr test. data were entered and analysed using microsoft excel version 16.0. since this study used detection of igm and igg antibodies, it is reasonable to determine the time gap between illness onset and result positivity. however, since onset of illness was unclear, time gap was defined as time between date of positive rt-pcr and the date rtk was conducted (pcr-rtk time gap). in total, we tested 23 patients (52.17% female). rtk1 was tested on 11 patients. rtk2 and rtk3 were tested simultaneously on the same 12 patients (table 1). participants’ age for rtk1 ranged from 12 to 70 years, and for rtk2/ rtk3, it ranged from 14 to 58 years. about half of the total participants (12/23 or 52%) were asymptomatic on presentation. the pcr-rtk time gap for rtk1 ranged from 18 to 34 days (median 26 days), whilst for rtk2 and rtk3, it ranged from 13 to 38 days (median 25.5 days). using rtk1, 5/11 (45.4%) patients produced positive igg results, and 1/11 (0.1%) patients showed positive igm result this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. kheng cheah and et. al 2 (figure 1). more patients (10/12 or 83.3%) had positive igg results using rtk3, but only one patient (0.08%) produced positive igm result. results were all negative for both igm and igg using rtk2. only one patient tested positive for both igm and igg antibodies using rtk3. both positive igm results were at day 29 after rt-pcr result was positive. fifty three percent (9/17) of positive rtk results were observed at day 21 to 30 after the diagnosis was confirmed by rt-pcr. based on our observations, patients tested igg positive earlier using rtk3 compared to rtk1. secondly, rtk2 did not produce positive results at all when rtk3 did. this reflects discrepancy in the performance of different rtks. in china, one study tested patients using combined igg and igm rtk. the rtk was 88.7% sensitive and 90.6% specific (2). while these figures seemed promising, a study using rtk in an ed in italy revealed a poor sensitivity of 18.4% and 91.7% specificity, making the rtk unreliable to diagnose covid-19 (3). possible explanation includes differences in antibody detection limit between rtks, undetectable low antibody titre during early stages of infection, and individual immune response such as immunocompromised states (2-4). these individual factors may be the reason why some patients tested negative for both igm and igg antibodies up to 26 days after a positive rt-pcr result (table 1). the time gap for the majority of igg positive patients was 11 to 30 days from positive rt-pcr results (figure 1). this is an expected finding since igg production is usually delayed. however, two patients tested igm positive at 29 days. while it is generally understood that igm is produced acutely and disappears two weeks after onset, research showed that in covid-19 infection, igm and igg production peaks in the third and fourth week (5), which corresponded to the time frame of our patients’ results. this study is limited by the small sample size. patient testing was based on convenience due to unpredictable kit availability, which only allowed researchers to use whichever kit was available in the laboratory at the time of testing. in conclusion, the rtks tested in this study yielded inconsistent results. health care providers and administrators should be aware that not all rtks produce accurate and reliable results. this warrants standardisation and fine tuning of covid-19 rtks. we suggest that pilot testing be done prior to selecting an rtk for use to ensure that they produce intended results. in fact, at the time of writing, the rtk2 batch used was recalled by its manufacturer due to faulty product following complaints from end-user. as enticing as it may be, health care authorities must consider this diagnostic option carefully and wisely. 1. declarations 1.1. acknowledgement the authors would like to thank the director general of health malaysia for the permission to publish this paper. 1.2. authors’ contributions pkc, cvh, hgl and pkc5 conceived and planned the study. fsz, mih, dfo and hgl collected the data and computed the findings. dfo and pkc5 wrote the letter. pkc and cvh were in charge of overall direction and planning. all authors discussed the findings and commented on the manuscript. 1.3. funding and supports the author(s) received no financial support for the research, authorship, and/or publication of this article. 1.4. conflict of interest none. 1.5. funding and support none. references 1. vashist sk. in vitro diagnostic assays for covid-19: recent advances and emerging trends. diagnostics. 2020;10(4):202. 2. li z, yi y, luo x, xiong n, liu y, li s, et al. development and clinical application of a rapid igm-igg combined antibody test for sars-cov-2 infection diagnosis. journal of medical virology. 2020;92(9):1518-24. 3. cassaniti i, novazzi f, giardina f, salinaro f, sachs m, perlini s, et al. performance of vivadiag covid-19 igm/igg rapid test is inadequate for diagnosis of covid-19 in acute patients referring to emergency room department. journal of medical virology. 2020;92(10):1724-7. 4. xiao at, gao c, zhang s. profile of specific antibodies to sars-cov-2: the first report. journal of infection. 2020;81(1):147-78. 5. du z, zhu f, guo f, yang b, wang t. detection of antibodies against sars-cov-2 in patients with covid-19. journal of medical virology. 2020;92(10):1735-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e9 table 1: results of three different rapid test kits (rtks) of covid-19 on 23 confirmed patients via rt-pcr age gender presentation pcr-rtk time gap rtk1 rtk2 rtk3 igm igm igm igm igm igm 52 male symptomatic exposure 13 negative negative negative positive 25 female asymptomatic close contact 15 negative negative negative negative 26 female asymptomatic exposure 15 negative negative negative positive 47 female asymptomatic exposure 15 negative negative negative negative 43 female symptomatic exposure 15 negative negative negative positive 48 female asymptomatic exposure 16 negative negative negative positive 53 female symptomatic exposure 16 negative negative negative positive 14 male symptomatic close contact 18 negative negative 21 female symptomatic close contact 19 negative negative 12 male asymptomatic close contact 21 negative positive 33 female asymptomatic close contact 21 negative positive 21 male asymptomatic close contact 21 negative negative 58 male symptomatic travel history 24 negative positive 21 male asymptomatic mass gathering 24 negative negative negative positive 28 female symptomatic mass gathering 25 negative negative 70 female asymptomatic close contact 25 negative positive 44 female symptomatic travel history 26 negative negative 58 male symptomatic travel history 27 negative negative negative positive 61 female asymptomatic close contact 29 positive negative 42 male symptomatic exposure 29 negative negative positive positive 14 male asymptomatic mass gathering 32 negative negative negative positive 65 male asymptomatic close contact 34 negative positive 26 male symptomatic mass gathering 38 negative negative negative positive this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. kheng cheah and et. al 4 figure 1: positive results produced by rtks based on the pcr-rtk time gap. only positive rtk1 and rtk3 results were included in this chart. all results for rtk2 were negative and thus omitted from this chart. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 130 emergency (2014); 2 (3): 130-133 original research an audit of emergency department accreditation based on joint commission international standards (jci) behrooz hashemi, maryam motamedi*, mania etemad, farhad rahmati, mohammad mehdi forouzanfar, fatemeh kaghazchi department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: despite thousands of years from creation of medical knowledge, it not much passes from founding the health care systems. accreditation is an effective mechanism for performance evaluation, quality enhancement, and the safety of health care systems. this study was conducted to assess the results of emergency department (ed) accreditation in shohadaye tajrish hospital, tehran, iran, 2013 in terms of domesticated standards of joint commission international (jci) standards. methods: this cohort study with a four-month follow up was conducted in the ed of shohadaye tajrish hospital in 2013. the standard evaluation checklist of iran hospitals (based on jci standards) included 24 heading and 337 subheading was used for this purpose. the effective possible causes of weak spots were found and their solutions considered. after correction, assessment of accreditation were repeated again. finally, the achieved results of two periods were analyzed using spss version 20. results: quality improvement, admission in department and patient assessment, competency and capability test for staffs, collection and analysis of data, training of patients, and facilities had the score of below 50%. the mean of total score for accreditation in ed in the first period was 60.4±30.15 percent and in the second period 68.9±22.9 (p=0.005). strategic plans, head of department, head nurse, resident physician, responsible nurse for the shift, and personnel file achieved the score of 100%. of total headings below 50% in the first period just in two cases, collection and analysis of data with growth of 40% as well as competency and capability test for staffs with growth of 17%, were reached to more than 50%. conclusion: based on findings of the present study, the ed of shohadaye tajrish hospital reached the score of below 50% in six heading of quality improvement, admission in department and patient assessment, competency and capability test for staffs, collection and analysis of data, training of patients, and facilities. while, the given score in strategic plans, head of department, head nurse, resident physician, responsible nurse for the shifts, and personnel file was 100%. key words: emergency service, hospital; accreditation; quality improvement; quality assurance, health care cite this article as: hashemi b, motamedi m, etemad m, rahmati f, forouzanfar mm, kaghazchi f. an audit of emergency department accreditation based on joint commission international standards (jci). emergency. 2014;2(3):130-3. introduction:1 espite thousands of years from creation of medical knowledge, it not much passes from founding the health care systems (1, 2). it could be said that the history of health care system in our country referred to the cyrus the great. in achaemenid court, two persons suffered from the same disease and the court physician had cured both of them. some months after their treatment, one of them died and another one was alive. cyrus the great prosecuted the physician for such a different out comes from the same disease. the physician proved that identical treatment was not applied for both of these patients and then, cyrus the *corresponding author: maryam motamedi; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel/fax: +982122721155; email: drmotamedimaryam@gmail.com received: may 2014; accepted: june 2014 great ordered to provide an established place under a standard control condition (3). in before centuries the superior service and health care was as attending the physician on patient bedside at home, while today the organizations are responsible to provide such health services. therefore, the quality of provided services depends on the quality process and organization systems in addition to specialist staffs and physicians (1). in such condition, accreditation is an effective mechanism for performance evaluation, quality enhancement, and the safety of health care systems. the selfevaluation process and outer evaluation of health care organizations, based on the defined standards, is called accreditation. accreditation is not only asses the standard conditions, but also has analytical, consulting, and recovery facets. some medical subjects based on evidences, medical ethics, reduce medical errors, and safed mailto:drmotamedimaryam@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 131 hashemi et al ty of the patient are included in a part of accreditation process (2). today, in developing countries governments use the accreditation as a tool for guarantee of care quality. the international standards, joint commission international (jci), is the base of accreditation in all over the world. lebanon has provided and applied the accreditation standards as a first country in east mediterranean. for the first time in iran at 1997, standards and evaluation criteria of general hospitals were published (1, 4). the accreditation standards in iran are taken from the last resources used in developed and developing countries and aligned with religious, cultural, and economical criteria as well as native conditions which their goal is quality enhancement, safety, and improving the responses in health system (2). this study was conducted to assess the results of emergency department (ed) accreditation in shohadaye tajrish hospital, tehran, iran, 2013 in terms of jci standards. methods: this cohort study with a four-month follow up was conducted in the ed of shohadaye tajrish hospital in 2013. for assessing the ed accreditation, a standard evaluation checklist of iran hospitals (designed based on jci standards) was used. this check list included 24 heading and 337 subheading as follow: strategic plans (six subheadings), head of department (two subheadings), ed head nurse (two subheadings), resident physician (five subheadings), responsible nurse for the shifts (two subheadings), personnel file (three subheadings), staff list (nine subheadings), justification of arrival period (four subheadings), staffs competency and capability test (nine subheadings), staffs training and empowering (25 subheadings), occupational health and safety, and environmental health booklet (six subheadings), policies and procedures (42 subheadings), admission and evaluation of the patient (25 subheadings), patient file (15 subheadings), assessment and ongoing care of patients (38 sub headings), drug instructions (62 subheadings), training of patients and their entourage (eight subheadings), sector support of para-clinic services (11 subheadings), resuscitation trolley (9 subheadings), facilities (19 subheadings), physical space (12 subheadings), physical safety (8 subheadings), quality improvement (5 subheadings), and collection and analysis of data (10 subheadings) (5). at first, the required training was provided for authorities and health sectors. for data gathering and internal audit the standard accreditation forms was used, delivered to hospitals by the health ministry. the accreditation team, included individuals who were trained by the same organ and from different positions, referred as a group to the department. accreditation was performed by the manager of accreditation and hospital quality improvement. the assessment was executed in two periods and by scoring to different categories, the results registered and analyzed. the score of each heading was defined between 0 and 100 based on the percentage. those headings had the score of below 50% were detected. in following, the effective possible causes of formation of weak spots were found and their solutions considered in future programs of the ed as an action plan to improve quality services. four months were taken to correct weaknesses and responsible individuals for each point determined. the accreditation of ed were repeated again by the same team after correction of problems. finally, the achieved results of two assessments were analyzed using descriptive statistics and spss version 20. results: the results of accreditation for two assessment are presented in figures 1 and 2. the six headings included strategic plans; head of department, head nurse, resident physician, responsible nurse for the shift, and personnel file had the score of 100% and not showed in the figures. in the first assessment, the lowest score belonged to the quality improvement heading (10%). quality improvement, admission in department and patient assessment, competency and capability test for staffs, collection and analysis of data, training of patients, and facilities had scores of below 50%. the mean of total ed accreditation score in the first period was 60.4±30.15 percent and in the second period 68.9±22.9 figure 1: the percentage of progress in performing the accreditation standards of emergency department.  figure 2: the percentages of progress in performing the accreditation standards of emergency department.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (3): 130-133 132 (p=0.005), (figure 3). just in two cases of whole headings below 50% in the first period, collection and analysis of data with growth of 40% as well as competency and capability tests for staffs with growth of 17%, reached to more than 50%. while despite of reaching a considerable score in the rest four cases, they could not success to achieve the least score of 50% (figure 4). discussion: based on findings of the present study, ed of shohadaye tajrish hospital was achieved scores of less than 50% in the first assessment for quality improvement, admission in department and patient assessment, competency and capability tests for staffs, collection and analysis of data, training of patients, and facilities. on the other hand, head of department, head nurse, resident physician, responsible nurse for the shift, and personnel file had the score of 100%. comparison of achieved scores in two periods was representative their increased trend in problematic cases and the most progression and reformation was performed in collection and analysis of data, quality improvement, and patient file. these mentioned headings were selected to develop due to their inexpensiveness and accessibility in the least time. for example, to eliminate the defects of patients' files a session was held with the responsible of training doctors and nurses as well as the head of hospital. in this session, the defects were introduced and then, the educational classes held for physicians and nurses to correct many defects of patients' files. noticing to the intended goal, improving scores to more than 50%, such a success just in two cases was achieved. a significant change was not seen (align with study objectives) in some headings like admission in department and patient assessment, quality improvement, and competency and capability tests for staffs; because these cases compared to financial issues needed more time to improve. for instance, holding the entrance exam requires extensive periodic tests. in addition, training of staffs from different occupational groups with various education levels is hard and time consuming. in the facilities heading, ups purchasing requires spending a high cost, which is not possible for the hospital to provide it in a short time. calendar schedule of six months for completing the competency and capability tests for staffs was designed by office of nursing for health sectors and office of quality improvement for support sectors; it is clear that their outcomes would be presented in the next assessments. after the first period of assessment in collection and analysis of data heading, the results of internal audit was analyzed and declared to management. noticing to the audit program declared to departments from center office of quality improvement, this procedure would be continued in future. admission in department and patient assessment headings were held in terms of calendar schedule and educational classes as well as performed extensively by office of nursing so that their improvement in the second assessment was remarkable. in a study, yarifard et al. showed that the most important administrative barriers of accreditation are the lack of awareness and training of hospital staffs in all accreditation levels as well as nonalignment and participation of administrators and faculty members. thus, the solution is training extension in all staff levels and involvement of senior managers in performing the programs (6). also, in another study establishment of an independent structure, as a national organization of accreditation to health services of iran, was introduced as a best and most effective way to improving the accreditation evaluation system of health services in country (2). karimi et al. study revealed that the department of biomedical engineering in the initial audit has the highest scale for observance of standards (41%) and imaging unit has the lowest (29%). three months after educational interventions in all departments of para clinic, the observance of standards has been increased by an average 18% and the most percentage of improvement was seen in imaging unit (12.2%) (7). bahadori and his colleges showed that hospital ownership type is not related to performance indicators(8). in addition, tayebi et al. didn't find any correlation between the evaluation score of emergency performance with hospital ownership type (3). moreover, churls et al. showed that accreditation level leads to change in six figure 3: total accreditation score percentage before and after intervention. *significant value: p<0.01.  figure 4: the percentage of progress in each branch after the second assessment.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 133 hashemi et al regions: administration and management, medical staff organization, review systems, organization of nursing services, physical facility and hospital role definition and planning (4, 9). lastly, it should be mentioned that despite of performing accreditation project tentatively since 2012 in hospitals, the results was not accounted in hospitals' evaluations. however, this issue has been seriously pursued since 2013 so that after data collection from all hospitals and retention of national average, the results were announced and hospital tariffs determined based on them. therefore, it is clear that because this topic is new, there are not many studies available in emergency medicine levels in iran. it hopes that the present study would be a step to perform this procedure in other emergencies and provide a possibility of comparison and analysis of differences among them. conclusion: based on findings of the present study, the ed of shohadaye tajrish hospital reached the score of below 50% in six headings of quality improvement, admission in department and patient assessment, competency and capability tests for staffs, collection and analysis of data, training of patients, and facilities. while, the given score in strategic plans, head of department, head nurse, resident physician, responsible nurse for the shifts, and personnel file was 100%. acknowledgments: this study is a part of the academic thesis of dr. fatemeh kaghazchi in shahid beheshti university of medical sciences. we would like to thank the head of ed, evaluation leaders, the head nurse of the department, and all those who helped us to conduct this study. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. benor de. faculty development, teacher training and teacher accreditation in medical education: twenty years from now. medical teacher. 2000;22(5):503-12. 2. commission j. hospital accreditation standards: joint commission resources; 2010. p. 17. 3. tabibi s, maleki m, movahednia s, gohari m. relationship between hospitals ownership and performance assessment score of emergency departments in the hospitals affiliated to iran university of medical sciences 2007. journal of health administration. 2009;12(36):25-32. 4. jaafaripooyan e, agrizzi d, akbari-haghighi f. healthcare accreditation systems: further perspectives on performance measures. int j qual health care. 2011;23(6):645-56. 5. shaw c, groene o, mora n, sunol r. accreditation and iso certification: do they explain differences in quality management in european hospitals? int j qual health care. 2010;22(6):445-51. 6. crawford l. senior management perceptions of project management competence. international journal of project management. 2005;23(1):7-16. 7. karmi m, amin a, vand mv, tahmasebi a, mosavi s, amini m, editors. audit and improve compliance with accreditation standards in ibn sina national hospital , tehran clinical units. first congress in clinical audit and quality improvement; 2012: tabriz university of medical sciences. 8. mohammad karim bahadori hr, shahram tofighi,ramin ravangard. accreditation of hospitals covered by performance indicators in lorestan university of medical sciences hospital. 2008;7(1):11-5. 9. el-jardali f, jamal d, dimassi h, ammar w, tchaghchaghian v. the impact of hospital accreditation on quality of care: perception of lebanese nurses. int j qual health care. 2008;20(5):363-71. emergency. 2017; 5 (1): e14 or i g i n a l re s e a rc h smartphones and medical applications in the emergency department daily practice amirhosein jahanshir1, ehsan karimialavijeh1∗, hojjat sheikh motahar vahedi1, mehdi momeni1 1. department of emergency medicine, dr. shariati hospital, tehran university of medical sciences, tehran, iran. received: april 2016; accepted: june 2016; published online: 9 january 2017 abstract: introduction: medical applications help physicians to make more rapid and evidence based decisions that may provide better patient care. this study aimed to determine the extent to which smart phones and medical applications are integrated in the emergency department daily practice. methods: in a cross sectional study, a modified standard questionnaire (payne et al.) consisting of demographic data and information regarding quality and quantity of smartphone and medical app utilization was sent to emergency-medicine residents and interns twice (two weeks apart), in january 2015. the questionnaire was put online using open access "web-form module" and the address of the web page was e-mailed along with a cover letter explaining the survey. finally, responses were analyzed using descriptive statistics and spss 22 software. results: 65 cases participated (response rate 86%). the mean age of interns and residents were 25.03 ± 1.13 and 30.27 ± 4.68 years, respectively (p < 0.001). there was no significant difference between interns and residents in owning a smartphone (p = 0.5). android was more popular than ios (67.7% against 25.8%) and the most popular medical apps were medscape and uptodate, respectively. 38 (61.3%) of the respondents were using their apps more than once a day and mostly for drug information. english (83.9%), persian (12.9%), and other languages (3.2%) were preferred languages for designing a medical software among the participants, respectively. conclusion: the findings of present study showed that smartphones are very popular among iranian interns and residents in emergency department and a substantial number of them own a smartphone and are using medical apps regularly in their clinical practice. keywords: smartphone; mobile applications; emergency service, hospital; evidence-based practice © copyright (2017) shahid beheshti university of medical sciences cite this article as: jahanshir a, karimialavijeh e, sheikh motahar vahedi h, momeni m. smartphones and medical applications in the emergency department daily practice. emergency. 2017; 5 (1): e14. 1. introduction today smartphones and tablets are universal, well known, and popular devices that are integrated into daily life of many people (1). by installing appropriate mobile applications on a smartphone or tablet, they will be capable of performing different tasks. app is short for application, and a mobile app is a software that has been designed to run on smartphones or tablets. apps can be downloaded from application distribution platforms (adp) such as google play, app store, windows phone store, and blackberry app world. international sanctions on iran led to development of local iranian app stores like bazaar and myket, which serve as sources of mo∗corresponding author: ehsan karimialavijeh; emergency department, dr. shariati hospital, kargar avenue, tehran, iran p.o box: 14117-13137 ; tel: +982161192240; fax: +982166904848 ; email: drkarimi86@gmail.com bile apps. for healthcare professionals, this novel technology provides an opportunity to promote patient care and decrease medical errors through rapid access to the latest evidence based medical information (2, 3). physicians use medical apps for different purposes such as: learning, education, decision making, medical calculation, and better interpretation of paraclinical tests (4-11). medical students are also very familiar with these handheld devices (12, 13). despite all benefits, several problems exist in this context. smartphones may have hardware limitations such as narrow screen, connectivity issues and so on. the reliability of medical apps is also under debate (14). the problem of app overload is another factor that may also confuse users in finding appropriate applications (15). based on the above mentioned, the present study aimed to investigate the extent of smartphone ownership and utilization of medical applications among interns and residents in an emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jahanshir et al. 2 2. methods 2.1. study design and setting this cross sectional study was performed in a teaching hospital of tehran university of medical sciences (tums) in iran, during january 2015. who met the inclusion criteria were contacted via 2 separate emails (two weeks apart). inclusion criteria consisted of 1. participation in tums emergency medicine training program; 2. registration of email address into the database of office of the vice chancellor for student affairs; 3. consent for use of mail address in correspondence with tums. the local ethical committee of tums approved the conduct of the study and researchers adhered to all helsinki recommendations and confidentiality of participants information. 2.2. data gathering initially, a modified version of payne et al. questionnaire of smartphones and medical apps use among medical students was developed (1). the questionnaire was translated into persian by the authors separately, and then the best translation for each item was chosen. statements about preferred apps and their user interface language were added, and one statement about current hospital of employment was deleted. medical apps were mentioned in the questionnaire, according to the researchers personal experience about their possible popularity. in order to establish face validity of the survey, an expert panel of emergency medicine professors, who were familiar with new technologies and medical applications, reviewed the final questionnaire and compared it with the original one. they suggested 2 minor revisions in translation and approved its content validity. 30 interns, who were in the emergency department rotation, were asked to fill the questionnaire as a pilot study. principle components analysis (pca) was performed and the cronbach’s alpha coefficient was calculated to evaluate the internal consistency of the survey. values higher than 0.6, were considered acceptable. the questionnaire was put online using open access "web-form module" in a website that was designed with "drupal platform", and the address of the web page as well as a cover letter explaining the survey were sent to 75 emergency department residents and interns by email and they were asked to fill it. responses were ip-sensitive and stored on a password-protected server. if any of the participants wanted to fill the questionnaire in an offline format, printed questionnaires were available. 2.3. data collection we collected data from patients electronic medical records and a regional icu database. for each patient with clinically and doppler proven dvt, key demographic and clinical characteristics including age, sex, diagnosis on admission, acute physiology and chronic health evaluation ii (apache ii) score, vte prophylaxis regimen, duration of mechanical ventilation, length of icu stay and patient’s outcome (discharge or death) were collected. to provide a uniform and unbiased assessment of doppler proven dvt, one research associate, who was a vascular surgeon, performed the doppler examination for all patients potentially having dvt and was blinded to the patients history and clinical status. all clinical decisions were made at the discretion of the icu team. potentially having dvt was defined as international classification of diseases, 9th revision, clinical modification (icd-9cm) codes (453.40, 453.41, 453.42, 453.80, and 453.90). 2.4. measured items 1. the number of smartphone owners among emergency medicine residents and interns. 2. the frequency of smartphone operating systems (ios, android, windows mobile, etc.). 3. the frequency of medical applications among smartphone owners. 4. the rate of medical app utilization among emergency medicine residents and interns. 2.5. statistical analysis data analysis was performed using spss version 22. data were analyzed using descriptive statistics. quantitative variables were reported as mean and standard deviation and qualitative ones as frequency and percentage. the results of the pilot study were not included in the final analysis. student t-test was used for comparing the mean age of interns and residents. p < 0.05 was considered statistically significant. 3. results: the survey of 65 participants (response rate 86%) was analyzed (50.8% female). 62 (95.38%) of them owned a smartphone. table 1 summarizes the baseline characteristics of participants. the mean age of interns and residents were 25.03 ± 1.13 and 30.27 ± 4.68 years, respectively (p < 0.001). there was no significant difference between interns and residents in owning a smartphone (p = 0.5). table 2 shows the popularity of smartphone operating systems and medical apps as well as frequency of their daily use and indications. android was more popular than ios (67.7% against 25.8%) and the most popular medical apps were medscape and uptodate, respectively. 38 (61.3%) of the respondents were using their apps more than once a day and mostly for drug information. figure 1 shows the distribution of medical apps installed on different smartphone operating systems (range 0 to 25 apps). although wikem was the only emergency medicine app that was mentioned in the questhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e14 table 1: baseline characteristics of the participants (n=65) items number (%) sex male 32 (49.2) female 33 (50.8) level of education interns 39 (60) 1th year resident 5 (7.7) 2nd year resident 15 (23.1) 3th year resident 6 (9.2) owned a smartphone yes 62 (95.4) no 3 (4.6) table 2: popularity of operating systems and medical apps among study participants variable (n = 62) number (%) operating systems android 42 (67.7) ios 16 (25.8) windows 4 (6.5) frequency of app use never 2 (3.2) rarely 4 (6.5) once a week 5 (8.1) 2-3 times a week 13 (21.0) 1-2 times a day 18 (29.0) many times a day 20 (32.3) medical apps medscape 53 (85.5) pubmed 7 (11.3) omnio 8 (12.9) wikem 1 (1.6) up to date 27 (43.5) others 12 (19.4) usage indication drug information 53 (85.5) differential diagnosis 27 (43.5) diagnosis 26 (41.9) treatment 38 (61.3) procedural skills 16 (25.8) others 9 (14.5) tionnaire, 61 (98.4%) participants had not installed it on their smartphones. english (83.9%), persian (12.9%), and other languages (3.2%) were preferred languages for designing a medical software among the participants, respectively. 4. discussion: the findings of the present study showed that smartphones are very popular among iranian interns and residents and a substantial number of them own a smartphone and are using medical apps regularly in their clinical practice. it was shown that using handheld computers and smartphones saves time and expedites decision making and treatment in both pre-hospital and hospital settings (2, 3, 16, 17). it also figure 1: distribution of installed apps and operating systems among the respondents. makes patient care more evidence based and prevents medication errors (3). in emergency medicine, there are guidelines and protocols to minimize wasted time in emergency situations, but when considering patient care, it is reasonable to spend a few moments on finding appropriate information. previous studies claimed that residents and younger physicians are more interested in using smartphones (18). although interns were significantly younger than residents in this study, no significant difference was found between them in owning smartphones. although it is easier to read a text in one’s native language, english was the most preferred language for designing a medical app among the respondents. in this study, most interns and residents were using medical apps for finding drug information and treatment options. although neither the information they needed to find on their smartphones nor the amount of time they spent on finding needed information were studied, it is thought that checking necessary information in a critical situation, e.g. epinephrine dose in anaphylaxis, might have a negative impact on patient outcome. an impact study is needed in this regard. no data could be found about market share of operating systems in iran. in 2014, the international data corporation (idc) stated that android, ios, windows phone and blackberry os have 76.6%, 19.7%, 2.8% and 0.4% of the worldwide smartphone market share, respectively (19). in this study, 25% of participants were using ios. the market share of operating systems is entirely related to brands and manufacturers. if we assume that the market share of these operating systems in iran is similar to what was found among the participants, then we can conclude that the market shares are not significantly different from idc report and international sanctions on iran could not change the market shares. this this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. jahanshir et al. 4 is mostly because 85% of smartphones and tablets are imported into iran illegally (20). although respondents stated that medscape and uptodate were the most used medical apps in their smartphones, but what they were using as uptodate was actually an offline version of uptodate website, which is not really an app. wikem, which is a free emergency medicine app, was not popular among the respondents. despite international sanctions on iran, which has restricted the access to app stores and some medical apps from iran, smartphones and medical apps are as popular as they are in other countries and iranian emergency physicians use them regularly in their clinical practice. it seems that purchasing a smartphone or installing a medical app, is a function of the physicians’ need rather than their age. although there are evidence that suggest the use of medical apps may improve patient care in the hospitals, this needs to be evaluated in emergency situations. in critical situations such as the emergency department and its acute area, using a medical app to find the best drug or its dose is time consuming and may defeat the purpose of patient safety. 5. limitations: only interns and residents were asked to fill out the questionnaire; therefore, the popularity of new technologies among younger people may interfere with the generalizability of the results of this study. 6. conclusion: the findings of the present study showed that smartphones are very popular among iranian interns and residents in emergency department and a substantial number of them own a smartphone and are using medical apps regularly in their clinical practice. 7. appendix 7.1. acknowledgements the authors wish to thank all of the interns and residents who participated in this study. 7.2. authors contribution all of the authors have equally contributed in designing and executing this study. dr. vahedi and dr. momeni have reviewed medical literature. dr. jahanshir and dr. karimi were responsible for analyzing the data and writing the article. 7.3. funding none. 7.4. conflict of interest the authors declare that they have no conflict of interest. references 1. payne kfb, wharrad h, watts k. smartphone and medical related app use among medical students and junior doctors in the united kingdom (uk): a regional survey. bmc medical informatics and decision making. 2012;12(121). 2. lindquist am, johansson pe, petersson gi, saveman bi, nilsson gc. the use of the personal digital assistant (pda) among personnel and students in health care: a review. j med internet res. 2008;10(4):e31. 3. prgomet m, georgiou a, westbrook ji. the impact of mobile handheld technology on hospital physicians’ work practices and patient care: a systematic review. j am med inform assoc. 2009;16(6):792-801. 4. modi j, sharma p, earl a, simpson m, mitchell jr, goyal m. iphone-based teleradiology for the diagnosis of acute cervico-dorsal spine trauma. can j neurol sci. 2010;37(6):849-54. 5. flannigan c, mcaloon j. students prescribing emergency drug infusions utilising smartphones outperform consultants using bnfcs. resuscitation. 2011;82(11):1424-7. 6. takao h, murayama y, ishibashi t, karagiozov kl, abe t. a new support system using a mobile device (smartphone) for diagnostic image display and treatment of stroke. stroke. 2012;43(1):236-9. 7. choudhri af, radvany mg. initial experience with a handheld device digital imaging and communications in medicine viewer: osirix mobile on the iphone. j digit imaging. 2011;24(2):184-9. 8. trelease rb. diffusion of innovations: smartphones and wireless anatomy learning resources. anat sci educ. 2008;1(6):233-9. 9. kubben pl, van santbrink h, cornips em, et al. an evidence-based mobile decision support system for subaxial cervical spine injury treatment. surg neurol int. 2011;2:32. 10. choi bg, mukherjee m, dala p, et al. interpretation of remotely downloaded pocket-size cardiac ultrasound images on a web-enabled smartphone: validation against workstation evaluation. j am soc echocardiogr. 2011;24(12):1325-30. 11. brunet p, cuggia m, le beux p. recording and podcasting of lectures for students of medical school. stud health technol inform. 2011;169:248-52. 12. ho k, lauscher hn, broudo m, et al. the impact of a personal digital assistant (pda) case log in a medical student clerkship. teach learn med. 2009;21(4):318-26. 13. torre dm, treat r, durning s, elnicki dm. comparing pdaand paper-based evaluation of the clinical skills of third-year students. wmj. 2011;110(1):9-13. 14. o’neill s, brady rr. colorectal smartphone apps: opporthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e14 tunities and risks. colorectal dis. 2012;14(9):e530-4. 15. van velsen l, beaujean dj, van gemert-pijnen je. why mobile health app overload drives us crazy, and how to restore the sanity. bmc med inform decis mak. 2013;13:23. 16. adams gl, campbell pt, adams jm, et al. effectiveness of prehospital wireless transmission of electrocardiograms to a cardiologist via hand-held device for patients with acute myocardial infarction (from the timely intervention in myocardial emergency, northeast experience [time-ne]). am j cardiol. 2006;98(9):1160-4. 17. clemmensen p, sejersten m, sillesen m, hampton d, wagner gs, loumann-nielsen s. diversion of stelevation myocardial infarction patients for primary angioplasty based on wireless prehospital 12-lead electrocardiographic transmission directly to the cardiologist’s handheld computer: a progress report. j electrocardiol. 2005;38(4 suppl):194-8. 18. garritty c, el emam k. who’s using pdas? estimates of pda use by health care providers: a systematic review of surveys. j med internet res. 2006;8(2):e7. 19. smartphone os market share q42014: the international data corporation (idc); 2014 [cited 2015 8/3/2015]. available from: http://www.idc.com/prodserv/smartphone-os-marketshare.jsp. 20. contraband cell phones: financial tribune; 2014 [cited 2015 8/3/2015]. available from: http://financialtribune.com/articles/economydomestic-economy/9878/contraband-cell-phones. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references emergency. 2017; 5 (1): e32 or i g i n a l re s e a rc h early vs late coronary angiography and intervention following thrombolytic therapy; a cohort study bahareh feizi1, shahram taghdisi1, jalil etemadi2∗ amir hossein feizi1, setareh asgarzadeh3, sepideh kamal1 1. clinical research development center, bouali hospital, islamic azad university, tehran medical sciences branch, tehran, iran. 2. cardiology department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3. clinical research development center, amir-almomenin hospital, islamic azad university, tehran medical sciences branch, tehran, iran. received: november 2016; accepted: december 2016; published online: 11 january 2017 abstract: introduction: the precise time of using percutaneous coronary intervention (pci) after fibrinolytic therapy for maximum efficiency and minimum side effects is still undetermined. therefore, the present study was designed to compare the outcome of myocardial infarction (mi) patients who underwent surgical intervention (angiography and pci) within 48 hours of thrombolytic therapy or after that. methods: the present study is a prospective cohort study aiming to compare the occurrence of no-reflow phenomenon, unstable angina, bleeding during intervention, and one month major adverse cardiac outcomes (recurrent mi, need for repeating surgical intervention, and mortality) between mi patents undergoing surgical intervention within the first 48 hours of or after 48 hours of thrombolytic therapy. results: 90 patients with the mean age of 54.97 ± 10.54 were studied (86.67% male). 50 (56%) patients underwent surgical intervention within 48 hours and 40 (44%) after that. the 2 groups were not significantly different regarding baseline characteristics. no-reflow phenomenon in the < 48 hours group was about twice the > 48 hours group (or = 0.35; 95% confidence interval: 0.14 – 0.92; p = 0.03), other outcomes were not significantly different. no case of mortality was seen in the 1 month follow up. conclusion: based on the results of the present study, it seems that no-reflow phenomenon rate is significantly lower in patients undergoing surgical intervention after 48 hours of fibrinolytic therapy. the difference between the two groups regarding prevalence of major adverse cardiac outcomes was not statistically significant. keywords: angiography; thrombolytic therapy; percutaneous coronary intervention; myocardial infarction; postoperative complications © copyright (2017) shahid beheshti university of medical sciences cite this article as: feizi b, taghdisi sh, etemadi j, feizi a, asgarzadeh s, kamal s. early vs late coronary angiography and intervention following thrombolytic therapy; a cohort study. emergency. 2017; 5(1): e32. 1. introduction c oronary artery disease (cad) and its associated side effects are the most common cause of mortality and disability all over the world and its cost burden is the highest among health care costs (1, 2). currently, each year 900 thousand people are affected with acute myocardial infarction (mi) in the united states, which brings about 225 thousand deaths(3). in the past, open-heart surgery was the major treatment for cad (4). yet, in recent years, coronary artery angioplasty through the skin has been proposed as an ∗corresponding author: jalil etemadi; cardiology department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 09143231444 email: jalil_md73@yahoo.com efficient treatment for st elevation mi (stemi)(5). unfortunately, many stemi patients either visit hospitals where percutaneous coronary intervention (pci) is not available, or are not referred to pci centers in the time range suggested by guidelines (6). in these cases, alternative treatment is using fibrinolytic agents such as tissue plasminogen activator and streptokinase. although according to the most recent guidelines of american heart association (aha), angiography and pci should be done within 3 to 24 hours of fibrinolytic therapy, evidence presented in it are derived from level b and c articles, which partially affects its reliability (6). initial studies have questioned effectiveness of pci and early angiography after fibrinolytic therapy (7, 8). yet, the power of the studies carried out in this regard are not high enough to confirm the effectiveness of this treatment (5, 9-11). consequently, the precise time of using pci after fibrinolytic therapy for maxthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. feizi et al. 2 imum efficiency and minimum side effects is still undetermined. therefore, the present study was designed to compare the outcome of mi patients who underwent surgical intervention (angiography and pci) within 48 hours of thrombolytic therapy or after that. 2. methods 2.1. study design and setting the present study is a prospective cohort study aiming to compare the outcome of mi patients who underwent surgical intervention (angiography and pci) either within the first 48 hours of or after 48 hours of undergoing thrombolytic therapy. the researchers adhered to the principles of helsinki declaration throughout the study and the protocol of the study was approved by the ethical committee of islamic azad university, medical sciences branch. 2.2. participants patients visiting the emergency department (ed) of bouali hospital, tehran, iran, who were diagnosed with stemi, were evaluated. patients over 18 years old, suffering from stemi, whose symptoms had initiated less than 12 hours ago, and had successful thrombolytic therapy were included. in contrast, those with underlying illnesses such as cancer, chronic hepatic and renal failure (creatinine > 250 mmol/l); pregnant women; drug and alcohol addicts; and those prohibited from using fibrinolytic therapy were excluded. after reaching diagnosis in ed, patients were sent to coronary care unit (ccu), where they underwent thrombolytic therapy and were scheduled for surgical intervention, based on patient condition and preference of in charge cardiologist. without any interferences from the researches, the participants were followed for 1 month regarding major adverse cardiac outcomes. 1-month follow-up was done by phone calls or inperson. after the follow-up period, patients were divided into 2 groups of < 48 hours and > 48 hours based on time interval between thrombolytic therapy and surgical interventions, and the surgical side effects and one month adverse cardiac outcomes were compared between the 2 groups. the time interval between initiation of fibrinolytic therapy and intervention was 3 to 48 hours in <48 hours group. 2.3. outcome patients were followed regarding no-reflow phenomenon, unstable angina, and bleeding during intervention, as well as one month major adverse cardiac outcomes including recurrent stemi or non-st elevation mi (nstemi), need for repeating surgical intervention, and mortality. 2.4. definitions -recurrent nstemi: presence of a q wave in 2 or more adjacent electrocardiogram leads accompanied by a rise in creatine kinase mb or troponin concentration to above the normal range and more than 50% of the previous measure 18 hours after surgical intervention. recurrent stemi: relapse of ischemia symptoms while resting, accompanied by st elevation of at least 0.1 millivolt in at least 2 adjacent electrocardiogram leads for more than 30 minutes during the first 18 hours after surgical intervention. unstable angina: chest pain while resting, with or without changes in electrocardiogram (ecg) and pain class (based on the classification of canadian cardiovascular society), or presence of dangerous arrhythmias such as atrial tachycardia and atrial fibrillation. no-reflow phenomenon: inadequate muscle perfusion without angiographic evidence of obstruction in a myocardial vessel (12). severity of hemorrhage during intervention was determined based on gust (global use of strategies to open coronary arteries) severity scale (13). 2.5. statistical analysis data were analyzed using spss version 20.0. qualitative data were presented as frequency and percentage and quantitative ones as mean ± standard deviation. student t-test was used for comparing means and chi-square or fisher’s exact tests for comparing categorical variables. in all analyzes p < 0.05 was considered as significance level. 3. results 90 patients with the mean age of 54.97 ± 10.54 were evaluated (86.67% male). 50 (56%) patients underwent surgical intervention within 48 hours and 40 (44%) after that. table 1 compares the baseline characteristics of patients in the 2 groups. the 2 groups were not significantly different regarding baseline characteristics. table 2 compares the frequency of outcomes in the groups, which showed a significant difference only regarding no-reflow phenomenon. this outcome in the < 48 hours group was about twice the > 48 hours group (p = 0.03). the odds ratio for occurrence of no-reflow phenomenon in patients who underwent surgical intervention after 48 hours of fibrinolytic therapy was significantly lower (or = 0.35; 95% confidence interval: 0.14 – 0.92; p = 0.03). 4. discussion the findings of this study showed that the frequency of adverse outcomes between mi patients undergoing surgical intervention (angiography and pci) within the first 48 hours and after 48 hours of receiving thrombolytic agents was not significantly different except for no-reflow phenomenon. in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e32 table 1: baseline characteristics in the studied groups variable first 48 hours (%) after 48 hours (%) p total (n=50) total (n=40) age (year) 55.5 ± 12.1 54.3 ± 10.9 0.63 sex (male) 43 (86.0) 35 (87.5) 0.84 medical history of diabetes mellitus 17 (34.0) 14 (35.0) 0.92 hypertension 22 (44.0) 14 (35.0) 0.39 hyperlipidemia 20 (40.0) 14 (35.0) 0.63 cardiovascular accident 7 (14.0) 5 (12.5) 0.84 myocardial infarction 13 (26.0) 7 (17.5) 0.34 smoking 25 (50.0) 24 (60.0) 0.4 ∗ data are presented as mean âś standard deviation or number and percentage. table 2: comparison of patient outcomes in the 2 groups complications first 48 hours (%) after 48 hours (%) p bleeding during intervention 1 (2) 0 (0.0) 0.56 no-reflow phenomenon 22 (44) 9 (22.5) 0.03 one month adverse cardiac outcomes recurrent myocardial infarction 1 (2) 0 (0.0) 0.56 repeating revascularization 0 (0.0) 0 (0.0) — mortality 0 (0.0) 0 (0.0) — other words, the odds of no-reflow phenomenon was significantly lower in patients who underwent surgical intervention after 48 hours. although the difference between other studied outcomes was not statistically significant, both cases of major adverse cardiac outcomes were seen in < 48 hours group. no mortality was seen in the 1-month follow-up. in the years before using stent, early pci has not been efficient and has been associated with side effects such as hemorrhage, mortality, and coronary artery re-occlusion (14, 15). however, using stents has significantly decreased post-pci coronary artery re-occlusion incidence (16, 17). this has encouraged doing pci immediately after fibrinolytic therapy (6, 18-20). as a result, the most recent guideline of aha has expressed that stemi patients should undergo pci as soon as possible. in cases that the patient has undergone fibrinolytic therapy, the ideal time for doing pci is within the first 24 hours, yet it should not be done in the first 2 – 3 hours (6). in a trial, armstrong et al. have expressed that early pci and angiography show better outcomes and fewer side effects compared to late pci (21). cantor et al. also believed that early pci is an efficient therapy with few side effects and the smaller the time interval between fibrinolytic therapy and pci, the better the results (14). in contrast, the findings of the present study showed that pci and angiography in the first 48 hours have more side effects compared to the second 48 hours. in line with this study, collet et al. in their meta-analysis showed that patients who undergo early pci show more side effects compared to those who undergo intervention after 24 or 48 hours (9). however, a study by edmond et al. showed that there is no difference between various time intervals of pci after fibrinolytic therapy, and results and side effects are similar (22). a review article by capodanno et al. revealed that pharmaco-invasive therapy is effective in stemi treatment and its time does not make a difference in the outcome of treatment or side effects (23). vant hof et al. did not detect a significant difference between early and after 48 hours pci (24). as can be seen, there is significant difference between study results, which might be due to differences in study design (cohort, clinical trial, or crosssectional), type of mi, type of thrombolytic used (streptokinase or t-pa), and not paying attention to outcomes such as no-reflow phenomenon. this variation in findings also reveals the need for further studies in this field. 5. limitation the power of the present study was low for comparing mortality rate and other side effects, except for no-reflow phenomenon between the two groups. 1-month follow-up done in the present study only evaluates the short-term adverse outcomes, while long-term follow-ups may enable more accurate assessment. long-term follow-up and designing further interventional studies is suggested. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. feizi et al. 4 6. conclusion based on the results of the present study, it seems that noreflow phenomenon rate is significantly lower in patients undergoing surgical intervention after 48 hours of fibrinolytic therapy. the difference between the two groups regarding prevalence of major adverse cardiac outcomes was not statistically significant. 7. appendix 7.1. acknowledgements authors would like to thank all the staff of emergency department and cardiac care unit of bouali hospital, tehran, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. murray cj, vos t, lozano r, naghavi m, flaxman ad, michaud c, et al. disability-adjusted life years (dalys) for 291 diseases and injuries in 21 regions, 1990âăş2010: a systematic analysis for the global burden of disease study 2010. the lancet. 2013;380(9859):2197-223. 2. yusuf s, reddy s, ounpuu s, anand s. global burden of cardiovascular diseases part i: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. circulation. 2001;104(22):2746-53. 3. grady d, herrington d, bittner v, blumenthal r, davidson m, hlatky m, et al. cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (hers ii). jama. 2002;288(1):49-57. 4. mathew v, berger pb, lennon rj, gersh bj, holmes dr. comparison of percutaneous interventions for unstable angina pectoris in patients with and without previous coronary artery bypass grafting. the american journal of cardiology. 2000;86(9):931-7. 5. keeley ec, boura ja, grines cl. primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. the lancet. 2003;361(9351):13-20. 6. de lemos ja, ettinger sm. 2013 accf/aha guideline for the management of st-elevation myocardial infarction: executive summary. journal of the american college of cardiology. 2013;61(4). 7. simoons m, betriu a, col j, von essen r, lubsen j, michel p, et al. thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. the lancet. 1988;331(8579):197-203. 8. rogers w, baim d, gore j, brown b, roberts r, williams d, et al. comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. results of the thrombolysis in myocardial infarction (timi) phase ii-a trial. circulation. 1990;81(5):1457-76. 9. collet j-p, montalescot g, le may m, borentain m, gershlick a. percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses approach according to the type of strategy. journal of the american college of cardiology. 2006;48(7):1326-35. 10. erne p, schoenenberger aw, burckhardt d, zuber m, kiowski w, buser pt, et al. effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the swissi ii randomized controlled trial. jama. 2007;297(18):1985-91. 11. steg pg, kerner a, van de werf f, lopez-sendon j, gore jm, fitzgerald g, et al. impact of in-hospital revascularization on survival in patients with non–st-elevation acute coronary syndrome and congestive heart failure. circulation. 2008;118(11):1163-71. 12. kloner ra, ganote ce, jennings rb. the “no-reflow” phenomenon after temporary coronary occlusion in the dog. j clin invest. 1974;54(6):1496. 13. simoons m, topol e, califf r, werf f, armstrong p, aylward pe, et al. an international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. new england journal of medicine. 1993;329(10):673-82. 14. cantor wj, burstein j, choi r, heffernan m, dzavik v, lazzam c, et al. transfer for urgent percutaneous coronary intervention early after thrombolysis for stelevation myocardial infarction: the transfer-ami pilot feasibility study. canadian journal of cardiology. 2006;22(13):1121-6. 15. arnold ae, serruys pw, rutsch w, simoons ml, de bono dp, tijssen jg, et al. reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. journal of the american college of cardiology. 1991;17(1):11-21. 16. sabatine ms, cannon cp, gibson cm, lopez-sendon jl, montalescot g, theroux p, et al. addition of clopidogrel this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e32 to aspirin and fibrinolytic therapy for myocardial infarction with st-segment elevation. new england journal of medicine. 2005;352(12):1179-89. 17. de luca g, suryapranata h, stone gw, antoniucci d, tcheng je, neumann f-j, et al. abciximab as adjunctive therapy to reperfusion in acute st-segment elevation myocardial infarction: a meta-analysis of randomized trials. jama. 2005;293(14):1759-65. 18. anderson jl, adams cd, antman em, bridges cr, califf rm, casey de, et al. 2012 accf/aha focused update incorporated into the accf/aha 2007 guidelines for the management of patients with unstable angina/nonâăşst-elevation myocardial infarction: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. journal of the american college of cardiology. 2013;61(23):e179-e347. 19. di mario c, dudek d, piscione f, mielecki w, savonitto s, murena e, et al. immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the combined abciximab reteplase stent study in acute myocardial infarction (caress-in-ami): an open, prospective, randomised, multicentre trial. the lancet. 2008;371(9612):559-68. 20. fernandez-aviles f, alonso jj, pena g, blanco j, alonsobriales j, lopez-mesa j, et al. primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with st-segment elevation: the gracia-2 non-inferiority, randomized, controlled trial. european heart journal. 2007;28(8):949-60. 21. armstrong pw, gershlick a, goldstein p, wilcox r, danays t, bluhmki e, et al. the strategic reperfusion early after myocardial infarction (stream) study. american heart journal. 2010;160(1):30-5. e1. 22. edmond jj, juergens cp, french jk. the pharmacoinvasive approach to stemi: when should fibrinolytictreated patients go to the “cath lab” postgraduate medical journal. 2009;85(1004):331-4. 23. capodanno d, dangas g. facilitated/pharmaco-invasive approaches in stemi. current cardiology reviews. 2012;8(3):177. 24. van’t hof aw, de vries st, dambrink j-he, miedema k, suryapranata h, hoorntje jc, et al. a comparison of two invasive strategies in patients with non-st elevation acute coronary syndromes: results of the early or late intervention in unstable angina (elisa) pilot study. european heart journal. 2003;24(15):1401-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6(1): e59 or i g i n a l re s e a rc h oral oxycodone compared with intravenous morphine sulfate for pain management of isolated limb trauma; a randomized clinical trial parisa eizadi1, mohammad jalili2∗, ahmadreza dehpour3 1. department of emergency medicine, tehran university of medical sciences, tehran, iran. 2. department of emergency medicine, imam hospital, tehran university of medical sciences, tehran, iran. 3. department of pharmacology, tehran university of medical sciences, tehran, iran. received: october 2018; accepted: november 2018; published online: 18 november 2018 abstract: introduction: appropriate pain relief enhances patient satisfaction and reduces patient anxiety. this study aimed to compare oral oxycodone with intravenous (iv ) morphine sulfate (ms) in pain management of acute limb trauma. methods: in this randomized double-blind clinical trial, patients over 14 years old, with acute isolated limb trauma were randomized to receive either 5mg iv ms or 5 mg oral oxycodone. pain intensity and adverse effects of medications were recorded 0, 30 and 60 minutes after drug administration and compared between the groups. results: 58 patients were studied. pain intensity was similar between the two studied groups at 30 minutes (p = 0.834) and 60 minutes (p = 0.880) after drug administration. furthermore, there was no significant difference between the two groups regarding decrease in pain within the defined time interval. drowsiness was reported more frequently in ms group after 30 minutes (p = 0.006). patients in ms group asked for more rescue analgesia. other adverse effects were similar in both groups. conclusion: oral oxycodone is as effective as iv morphine sulfate in treatment of acute musculoskeletal pain following blunt limb trauma. keywords: oxycodone; morphine; wounds and injuries; acute pain © copyright (2018) shahid beheshti university of medical sciences cite this article as: eizadi p, jalili m, dehpour a. oral oxycodone compared with intravenous morphine sulfate for pain management of isolated limb trauma; a randomized clinical trial. emergency. 2018; 6(1): e59. 1. introduction pain is an unpleasant emotional and sensory experience and the most common cause of emergency department (ed) visits. in the united states, almost 40 million ed visitors looked for analgesics for relief of acute pain in one year (1, 2). appropriate pain relief enhances patient satisfaction and reduces patient anxiety (2, 3). hence, effective management of acute pain is one of the most important aspects of emergency physicians’ practice (2, 4). one acceptable approach for pain management in the ed is administration of effective drugs with minimal side effects, through an appropriate route. several therapeutic agents have been used including acetaminophen (paraceta∗corresponding author: mohammad jalili; emergency department, imam hospital, keshavarz boulevard, tehran, iran. email: mjalili@tums.ac.ir tel: 00982166904848, fax: 00982161192240 mol), non-steroidal anti-inflammatory drugs (nsaids), opioids and synthetic drugs with narcotic properties (3). mild to moderate pain is usually controlled by non-opioid agents, while opioid analgesics are used to reduce moderate-tosevere pain (5). intravenous (iv ) morphine sulfate (ms) is a common and effective analgesic agent, used for management of moderate to severe pain in ed (6-8). however, some potential side effects such as respiratory and central nervous system depression, nausea and vomiting and pruritus have been reported (6-8). yet another feature that can limit the utility of ms as an ideal analgesic in the ed is its iv form of administration. therefore, agents that do not require iv line placement could potentially be the preferred approach for initiation of pain treatment (7). oxycodone is a semisynthetic analgesic opioid and an agonist of mu, kappa and delta receptors (1, 5, 6, 9). mu receptors are known to be responsible for analgesia (µ1), sedation, euphoria and its side effects include pruritus, vomiting and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. eizadi et al. 2 respiratory depression (µ2). furthermore, kappa receptors are responsible for analgesia, dyspnea, dysphoria, urinary retention, and meiosis while delta receptors have spinal analgesic effects (10). oxycodone is a potent opioid with high oral bioavailability, rapid absorption and predictable effects (1, 6, 9). compared to morphine, oxycodone has a greater analgesic potency and a shorter half-life. its onset of action is 1 hour after administration and peak plasma concentration is achieved within 90 minutes (1, 5, 6). although oxycodone and morphine share some characteristics such as increased tolerance and addictive potential, (1) easy titration, predictable metabolism, less toxicity and less sedation distinguish oxycodone from morphine (6, 9, 11). oxycodone produces less hallucination, nausea and pruritus compared to morphine and it does not affect arterial pressure and heart rate (1, 5, 6). an overview of prior literature highlighted the lack of studies about use of oral oxycodone in the field of acute trauma. the majority of reports are about chronic pain or in settings other than the ed (12). this study was designed to compare ease of administration, efficacy and safety of oral oxycodone with those of iv morphine sulfate in sequential time points after drug administration in patients with acute limb trauma. 2. methods 2.1. study design and setting this is a randomized, double-blind placebo controlled clinical trial that was approved and monitored by the ethics committee of tehran university of medical sciences (ethics reference number: 54352). the study was conducted in the emergency department of a tertiary teaching hospital (imam khomeini), tehran, iran, from july 2014 to march 2015. the trial was officially registered in irct.ir (registration number: irct201204089387n2). written informed consent was obtained from all patients before enrolment. 2.2. participants eligible participants were adult patients aged 14 or above with moderate to severe pain (numerical rating scale [nrs] more than 3) following isolated limb trauma. we excluded patients with altered consciousness, severe chronic disease (liver, kidney and respiratory), previous history of allergy to opioids, recent opioid use and pregnant patients. 2.3. intervention: participants were randomized to receive either 5 mg oral oxycodone hydrochloride plus 5ml iv injection of normal saline or 5 ml equivalent to 5 mg injection of iv ms and oral placebo. block randomization using computer generated blocks of four was used to assign patients to each group. drugs were prepared and sealed in consecutively numbered envelops by a research assistant who was not involved in drug administration. patients’ enrollment, drug administration and data collection were done by another trained research assistant. research assistants were medical students and they were trained for the study objectives. patients and assistants who administrated drugs and collected data remained blinded to study groups during the study. 2.4. data gathering prior to drug administration demographic features and mechanism of trauma were registered in data collection sheets. participants were asked to score the pain severity from 0 to 10. eligible patients received either drug. data were collected at 0, 30 and 60 minutes after patients received analgesics. 2.5. outcome assessment primary outcome of this study was pain relief and was assessed by nrs at exact time points. secondary outcomes including changes in blood pressure, dizziness, pruritus, nausea and vomiting were also monitored and registered simultaneously. 2.6. statistical analysis based on previous studies, which showed standard deviation of 1.7 in the population (2), and considering an effect size of 1.3, we estimated that sample size of 28 patients in each group will give a power of 80% and two side type one error of 5% to detect a significant difference. descriptive analysis was used to compare basic features in the two groups. one way anova and general linear mode were used to analyze outcomes between and within groups. the study result analysis was based on per protocol method. data were analyzed using spss 20 statistical software and intension to treat analysis approach. 3. results 3.1. characteristics of the study population 80 patients were assessed for eligibility; 20 of which were excluded from the study. sixty patients were enrolled and randomly allocated to either oxycodone or ms group. trial subjects flow is shown in figure 1. participants’ main characteristics are shown in table 1. baseline characteristics were similar between the two groups. 3.2. comparison of two groups mean pain score in ms group was 8.32 ± 1.36 at the time 0, reached 5.71 ± 2.39 at 30 minutes, and 4.75 ± 2.24 at 60 minutes after drug administration (p < 0.001). also mean pain score in oxycodone group was 7.35 ± 1.55 at the time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6(1): e59 table 1: baseline characteristics of studied participants characteristics morphine sulfate (n=28) oxycodone (n=30) p value age mean ± standard deviation 32.86 ± 15.39 29.27 ± 9.35 0.432 sex male 23 (82.10) 20 (66.67) 0.179 female 5 (17.90) 10(33.33) mechanism of injury direct trauma 1 (3.60) 5 (16.70) mva 10 (35.70) 13 (43.30) 0.226 falling 14 (50.00) 11 (36.70) cpa 3 (10.7) 1 (3.30) data were presented as mean ± standard deviation or frequency (%). mva: motor vehicle accidents; cpa: car pedestrian accident table 2: comparison of pain severity between groups in 0, 30, and 60 minutes after drug administration time (minute) median mean ± sd sem p value 0 morphine sulfate 9 8.32 ± 1.36 0.257 0.045 oxycodone 8 7.53 ± 1.55 0.282 30 morphine sulfate 6 5.71 ± 2.39 0.450 0.834 oxycodone 6 5.83 ± 1.89 0.346 60 morphine sulfate 4 4.75 ± 2.24 0.422 0.880 oxycodone 5 4.83 ± 1.93 0.352 differences 0-30 morphine sulfate -2.8214 1.96362 0.37109 0.078 oxycodone -1.7333 1.55216 0.28338 differences 30-60 morphine sulfate -0.7857 0.99469 0.18798 0.903 oxycodone -0.9667 0.92786 0.16940 differences 0-60 morphine sulfate -3.5000 1.68874 0.31914 0.110 oxycodone -2.7000 1.91455 0.34955 sem, standard error of mean; sd: standard deviation. table 3: frequency of adverse event occurrence in the studied groups adverse event oxycodone morphine sulfate p value hypotension 30 minute 7 (23.30) 3 (10.70) 0.301 60 minute 8 (26.70) 4 (14.30) 0.336 nausea 30 minute 2 (6.70) 6 (21.40) 0.138 60 minute 2 (6.70) 4 (14.30) 0.415 dizziness 30 minute 3 (10.00) 12 (42.90) 0.006 60 minute 11 (36.70) 11 (39.30) 1.000 rescue analgesic 30 minute 60 minute 1(3.30) 8(28.60) 0.011 0, reached 5.83 ± 1.89 at 30 minutes, and 4.83 ± 1.93 at 60 minutes after drug administration (p < 0.001). although there was a 0.81 difference in pain score between the two study groups at the time 0, there was no significant difference bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. eizadi et al. 4 tween groups 30 and 60 minutes after administration of medications (table 2, figure 2). 3.3. secondary outcomes dizziness was reported more frequently in morphine sulfate group compared to oxycodone group. eight participants asked for rescue analgesic in morphine group, while only one patient asked for more analgesia in oxycodone group. other adverse effects were similar in both groups (table 3). there were no cases of seizure, respiratory depression or loss of consciousness. no naloxone was administrated during the study. 4. discussion: the results of the current study demonstrate that oral oxycodone is as effective as iv ms in relieving pain of patients with acute limb trauma. considering pain score at the time points of 30 minutes and 60 minutes after drug administration, no significant differences were observed between the two groups. to minimize the effect of the mentioned disparity, we analyzed the amount of decrease in pain score in specific time intervals. the result was similar and the analgesic effects of these two opioids were comparable. a limited number of studies have compared oxycodone with morphine sulfate. the findings of our study are compatible with the study conducted by miner et al. in their study, patients received either 0.125 mg/kg oral solution of oxycodone or 0.1 mg/kg iv morphine sulfate. pain score, adverse effects, onset of action and time to administration of drugs were assessed in patients with acute musculoskeletal pains in sequential time intervals (7). result of that study, similar to our findings, highlighted that the pain scores of the two study groups were similar 30 minutes after drug administration. the results of our study are also similar to the study by pedersen et al. although the results were comparable, the design of their study was different from ours. they studied analgesic effects of morphine and oxycodone, both in dose of 0.1 mg/kg, 4 hours after percutaneous kidney stone surgery (11). pain score and side effects of medications were assessed every 15 minutes. oxycodone appeared to be similar to morphine in analgesia 4 hours after surgery. in our study, drowsiness was reported more frequently at time point of 30 minutes by patients who received morphine sulfate while the distinction between the two groups was less obvious at time point of 60 minutes. kalso, in a study in 1991, mentioned more drowsiness in patients who received morphine for post-surgical pain treatment compared to patients who received oxycodone (13). other adverse effects were similar in both groups according to our study. patients in morphine sulfate group asked for more rescue analgesic. figure 1: study participants’ flow diagram. figure 2: pain score changes during study period (p > 0.05). 5. limitations we believe that our study faced a number of limitations. firstly, the sampling of our patients could have been affected by the following conditions: in crowded eds most patients with acute isolated limb trauma are managed as outpatients and they receive prescribed analgesics at home. our study population consisted of admitted patients and hence the results may not be applicable to an outpatient population. furthermore, we conducted the study in a single center. secondly, we administerated a single dose of 5mg for both morphine sulfate and oxycodone groups instead of adjusting the dosage to the weight. although the dosage effectively reduced pain; the fact is that the side effects of opioids occur in higher doses. for more accurate comparison of side effects between the two drugs, higher doses should be administrated. thirdly, we used nrs for pain scoring. it is possible that some patients mentioned higher pain score in order to accelerate the services they would receive. finally, although this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6(1): e59 we had randomly allocated the patients to either group, the final groups were significantly different regarding sex. as a result of our randomization, there were significant discordance between sex distribution of the two groups and this can be considered as a confounding factor. considering the fact that there is potential sex difference in analgesic effects of opioids (14-18), result of this study should be interpreted cautiously. 6. conclusion to sum up, oral oxycodone is as effective as iv morphine sulfate in management of acute pain following limb trauma. it can be considered as an appropriate alternative for iv morphine sulfate in crowded eds, where placing an iv line may be time-consuming. 7. appendix 7.1. acknowledgements this study has been supported by tehran university of medical sciences and health service (grant no: 91-1-30-15974). we would like to thank dr. ghazale keshvadi and dr. amir eslami for assistance in data gathering. we would also like to show our gratitude to shafa pharmaceutical and hygienic company for providing us with placebos. 7.2. author contribution all persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other journal. specific contributions made by each author are listed as below: mohammad jalili: study concept and design, critical revision of the manuscript for important intellectual content, and acquisition of funding ahmad reza dehpour: study concept and design, critical revision of the manuscript for important intellectual content parisa eizadi: study concept and design, acquisition of the data, analysis and interpretation of the data, statistical expertise, drafting of the manuscript authors’ orcids parisa eizadi: 0000-0001-6587-7426 mohammad jalili: 0000-0002-0689-5437 ahmadreza dehpour: 0000-0002-8001-5565 7.3. funding/support none. 7.4. conflict of interest the authors of this study certify that they have no involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. references 1. v. oldfield, c.m. perry, oxycodone/ibuprofen combination tablet, drugs, 65 (2005) 2337-2354. 2. c.a. marco, m.c. plewa, n. buderer, c. black, a. roberts, comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: a double-blind, randomized, controlled trial, academic emergency medicine, 12 (2005) 282-288. 3. n.d. moore, in search of an ideal analgesic for common acute pain, acute pain, 11 (2009) 129-137. 4. s.j. lovell, t. taira, e. rodriguez, a. wackett, j. gulla, a.j. singer, comparison of valdecoxib and an oxycodone– acetaminophen combination for acute musculoskeletal pain in the emergency department: a randomized controlled trial, academic emergency medicine, 11 (2004) 1278-1282. 5. i.a. dhalla, m.m. mamdani, m.l. sivilotti, a. kopp, o. qureshi, d.n. juurlink, prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone, canadian medical association journal, 181 (2009) 891-896. 6. m.a. zare, a.h. ghalyaie, m. fathi, d. farsi, s. abbasi, p. hafezimoghadam, oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate in acute bone fracture pain control: a doubleblind placebo-controlled randomized clinical trial, european journal of orthopaedic surgery & traumatology, 24 (2014) 1305-1309. 7. j.r. miner, j. moore, r.o. gray, l. skinner, m.h. biros, oral versus intravenous opioid dosing for the initial treatment of acute musculoskeletal pain in the emergency department, academic emergency medicine, 15 (2008) 1234-1240. 8. o. ahmadi, m.n. isfahani, a. feizi, comparing lowdose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture, journal of research in medical sciences: the official journal of isfahan university of medical sciences, 19 (2014) 502. 9. f. franceschi, m. marini, s. ursella, l. carbone, m. candelli, g. pignataro, e. al, use of oxycodone in polytrauma patients: the“gemelli”experience, european review for medical and pharmacological sciences, 12 (2008) 123. 10. a.m. trescot, s. datta, m. lee, h. hansen, opioid pharmacology, pain physician, 11 (2008) s133-153. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. eizadi et al. 6 11. k.v. pedersen, a.e. olesen, a.m. drewes, p.j.s. osther, morphine versus oxycodone analgesia after percutaneous kidney stone surgery, urolithiasis, 41 (2013) 423430. 12. z. al dabbagh, k.-a. jansson, c.-o. stiller, s. montgomery, r.j. weiss, no signs of dose escalations of potent opioids prescribed after tibial shaft fractures: a study of swedish national registries, bmc anesthesiology, 14 (2014) 1. 13. e. kalso, r. poyhia, p. onnela, k. linko, i. tigerstedt, t. tammisto, intravenous morphine and oxycodone for pain after abdominal surgery, acta anaesthesiologica scandinavica, 35 (1991) 642-646. 14. m. niesters, a. dahan, b. kest, j. zacny, t. stijnen, l. aarts, e. sarton, do sex differences exist in opioid analgesia? a systematic review and meta-analysis of human experimental and clinical studies, pain, 151 (2010) 61-68. 15. e. sarton, e. olofsen, r. romberg, j. den hartigh, b. kest, d. nieuwenhuijs, a. burm, l. teppema, a. dahan, sex differences in morphine analgesiaan experimental study in healthy volunteers, the journal of the american society of anesthesiologists, 93 (2000) 1245-1254. 16. j.-k. zubieta, r.f. dannals, j.j. frost, gender and age influences on human brain mu-opioid receptor binding measured by pet, american journal of psychiatry, 156 (1999) 842-848. 17. j.-k. zubieta, y.r. smith, j.a. bueller, y. xu, m.r. kilbourn, d.m. jewett, c.r. meyer, r.a. koeppe, c.s. stohler, îij-opioid receptor-mediated antinociceptive responses differ in men and women, journal of neuroscience, 22 (2002) 5100-5107. 18. t.n. andreassen, p. klepstad, a. davies, k. bjordal, s. lundstrom, s. kaasa, o. dale, influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients, european journal of clinical pharmacology, 67 (2011) 493-506. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion: limitations conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e42 le t t e r to ed i to r rapid and deep versus normal breathing in salbutamol inhalation effectiveness; a letter to editor faeze zeinali1, naser mohammad karimi1∗ mohamadali jafari1, ebrahim akbarzadeh moghadam1, 1. emergency medicine department, shahid sadoughi hospital ,shahid sadoughi university of medical sciences, yazd, iran. received: april 2021; accepted: april 2021; published online: 26 may 2021 cite this article as: zeinali f, mohammad karimi n, jafari m, akbarzadeh moghadam e. rapid and deep versus normal breathing in salbutamol inhalation effectiveness; a letter to editor. arch acad emerg med. 2021; 9(1): e42. https://doi.org/10.22037/aaem.v9i1.1122 dear editor, metered dose inhalers (mdis) are widely used in the management of patients with asthma and choronoc obstractyive polmunary disease (copd). studies comparing the efficacy of inhalers versus nebulizers have shown no significant difference (1, 2). good inhaler technique is essential to improve patient compliance and control of symptom, and diminish side effects. the usual technique is to use 5 tidal breaths. the global initiative for asthma guidelines suggest that patients can take a slow and single breath to inhale the drug or do tidal breathing. the total lung deposition of an inhaled treatment is strongly affected by the speed of inhalation. for ideal drug delivery, it is vital that the inspiratory flow at the beginig of inhalation is fast enough to break up the formulation of the metered dose to yield particles of a size distribution that will enter the peripheral airways (3-5). failure to attain this high internal force increases the likelihood of the dose affecting the oropharynx. errors in inhaler technique are linked with lower drug deposition to the lungs and poor clinical control, and may lead to increased emergency ward admissions and higher treatment costs (6, 7). the authors of this letter compared the effectiveness of two inhalation methods of salbutamol spray (rapid and deep breathing vesrus normal breathing with tital volume) in management of patients with respiratoty distrease in emergency department. this randomized clinical trial was conducted on 14 to 75 year-old patients who visited the emergency department of shahid sadoughi hospitals, yazd, iran, with asthma exacerbation. the patients were randomly divided into two inhalation technique groups using simple random sampling. one group received 200µg salbutamol (us∗corresponding author: naser mohamad karimi; emergency department, shahid sadoughi hospital, shahid ghandy blvd, ebne sina ave, yazd, iran. postal code: 8915887857, email: nmkarimi1310@gmail.com. mobile: 00989132749231, fax: 0098-353-8224100, orcid: https://orcid.org/00000003-1108-3625 ing salbutamol mdi) via rapid and deep breathing and another group received the same amount through 5 normal tidal breaths. all patients gave informed consent and the protocol of the investigation was approved by the local ethics committee (ethics code:ir.ssu.medicine.rec.1395.181). this trial was registred in iranian registry of clinical trials (irct20171531038154n1). peak expiratory flow (pef) was determined before and 5, 10, and 15 minutes after inhaling 200µg salbutamol in both groups. 110 patients with the mean age of 39.5 ±16.7 years were randomly assigned to two groups (52% males). the two groups were similar regarding gender (p 0.088), age (p = 0.083), and mean baseline pef (p = 0.75). mean pef rates of the two groups at baseline and 5, 10 and 15 minutes after salbutamol administration are presented in table 1. significant improvment in pef, from baseline to after intervention, was observed in both groups (p < 0.001). in addition, a significant improvement was observed in pef, from 5 minutes to 10 and 15 minutes after treatment in both groups (p < 0.001). however, pef was not significantly different between groups 5 (p = 0.56), 10 (p = 0.18), and 15 (p = 0.10) minutes after treatment. boskabady’s study showed that giving proper technique instruction to asthmatic patients could improve bronchodilator responses, such as an increase in pef (8). rahmati et al. showed that proper use of mdi, with or without spacer, could increase pef in asthmatic patients (9). patients can take a slow single inhalation instead of tidal breathing (10). stephen et al. did a randomized controlled trial to exibit that there was no clinically significant difference between pef with one maximum dose inhalation and then breath-holding and 5 tidal breaths at the time of salbutamol inhalation using mdi in 82 asthmatic children 5–15 years of age (11). another study by schultz et al. evaluated the number of inhalations required to inhale salbutamol from various spacers/valved holding chambers. they concluded that one maximal dose inhalation (without breath-hold) did not improve this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. zeinali et al. 2 table 1: comparing the peak of expiratory flow (pef) between the two groups at baseline and different times after treatment time groups (breathinhg method) p value normal rapid and deep baseline 266.0 ± 81.7 261.0 ± 98.0 0.75 5 minutes 302.0 ± 86.74 292.0 ± 104.0 0.56 10 minutes 331.0 ± 92.1 304.0 ± 107.0 0.18 15 minutes 342.0 ± 100.0 309.0 ± 109.0 0.10 data are presented as mean ± standard deviation. delivery of drug in comparison with tidal breathing, which is in compliance with the discovery of our study (12). a similar study demonstrated that bronchodilators delivered by mdi via nebuhaler have comparable outcome when given by six tidal breaths or the more difficult two maximum breaths plus breath-hold (13). inhaler technique assessment is an elemental part of the ordinary treatment of anybody suffering from asthma or copd. for inhaled medicines such as salbutamol, additional attention to the application technique is needed to select the best dosage, but there are very few studies on this subject to estimate the effectiveness of each method. previously, studies have shown that a considerable portion of patients do not operate/use their inhaler devices correctly (7, 14-16), this may contribute to reduction of medication delivery and poor disease control (17-20). in this regard, the most frequent error observed with using mdi was the step of waiting for 30 seconds between inhalations. lack of proper exhalation prior to inhalation was reported in 25% of the inhaler users (6). educational aids could be effective in this process (21), but many patients may use their devices incorrectly even after training. our study suggests that rapid and deep inhalation without a breath-hold technique is not better than 5 tidal breaths technique in correcting pef in those suffering from asthma. therefore, patients should be given consultations for choosing the most appropriate technique for them when using inhaled medications. the data of this study may not be generalizable, because it was a single-hospital-based study. another limitation of this study was that we did not assess the side effects of the two methods. 1. declarations 1.1. acknowledgment the authors would like to thank dr. s.mahmood hosseini and miss amineh brumand for their valuable comments on english writing of the manuscript. 1.2. authors’ contributions naser mohamad karimi designed the study, collected the data, and performed analysis. faeze zeinali.n performed the analysis, wrote the draft and submitted the manuscript. both athours read and confirmed the final version of the manuscript before submission. 1.3. conflicts of interest there was no financial payment to the authors for writing this manuscript, and there is no conflict of interest about this article. 1.4. funding support none. references 1. hosseini m, almasi-hashiani a, sepidarkish m, maroufizadeh s. global prevalence of asthma-copd overlap (aco) in the general population: a systematic review and meta-analysis. respiratory research. 2019;20(1):229. 2. mahler da, ohar ja, barnes 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d, vatsa m, lodha r, kabra sk. a randomized controlled trial of 2 inhalation methods when using a pressurized metered dose inhaler with valved holding chamber. respiratory care. 2015;60(12):1743-8. 12. schultz a, le souëf tj, venter a, zhang g, devadason sg, le souëf pn. aerosol inhalation from spacers and valved holding chambers requires few tidal breaths for children. pediatrics. 2010;126(6):e1493-e8. 13. eiser n, phillips c, wooler p. does the mode of inhalation affect the bronchodilator response in patients with severe copd? respiratory medicine. 2001;95(6):476-83. 14. price d, bosnic-anticevich s, briggs a, chrystyn h, rand c, scheuch g, et al. inhaler competence in asthma: common errors, barriers to use and recommended solutions. respiratory medicine. 2013;107(1):37-46. 15. sanchis j, gich i, pedersen s, team admi. systematic review of errors in inhaler use: has patient technique improved over time? chest. 2016;150(2):394-406. 16. cho-reyes s, celli br, dembek c, yeh k, navaie m. inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of us studies. chronic obstructive pulmonary diseases: journal of the copd foundation. 2019;6(3):267. 17. national ae, prevention p. expert panel report 3 (epr-3): guidelines for the diagnosis and management of asthmasummary report 2007. the journal of allergy and clinical immunology. 2007;120(5 suppl):s94. 18. gebremariam th, binegdie ab, mitiku as, ashagrie aw, gebrehiwot kg, huluka dk, et al. level of asthma control and risk factors for poor asthma control among clinic patients seen at a referral hospital in addis ababa, ethiopia. bmc research notes. 2017;10(1):1-6. 19. chogtu b, holla s, magazine r, kamath a. evaluation of relationship of inhaler technique with asthma control and quality of life. indian journal of pharmacology. 2017;49(1):110. 20. ilic ad, zugic v, zvezdin b, kopitovic i, cekerevac i, cupurdija v, et al. influence of inhaler technique on asthma and copd control: a multicenter experience. international journal of chronic obstructive pulmonary disease. 2016;11:2509. 21. guevara jp, wolf fm, grum cm, clark nm. effects of educational interventions for self management of asthma in children and adolescents: systematic review and metaanalysis. bmj. 2003;326(7402):1308-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency. 2017; 5 (1): e29 or i g i n a l re s e a rc h intravenous amiodarone versus digoxin in atrial fibrillation rate control; a clinical trial majid shojaee1, bahareh feizi2∗. reza miri3, jalil etemadi3, amir hossein feizi2 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, bouali hospital, islamic azad university, tehran medical sciences branch, tehran, iran. 3. cardiology department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: october 2016; accepted: november 2016; published online: 10 january 2017 abstract: introduction: treatment of rapid ventricular response arterial fibrillation (rapid af) varies depending on the decision of the in-charge physician, condition of the patient, availability of the drug, and the treatment protocol of the hospital. the present study was designed aiming to compare iv digoxin and amiodarone in controlling the heart rate of patients presenting to emergency department with rapid af and relative contraindication for first line drug in this regard. methods: in the present clinical trial, patients presented to the ed with rapid af and relative contraindication for calcium channel blockers and beta-blockers were treated with either iv amiodarone or iv digoxin and compared regarding success rate and complication using spss version 22. p < 0.05 was considered as statistically significant. results: 84 patients were randomly allocated to either amiodarone or digoxin treatment groups of 42 (53.6% male). the mean age of the studied patients was 61.8 ± 11.14 years (38 79). no significant difference was present regarding baseline characteristics. the rate of treatment failure was 21.4% (9 cases) in amiodarone and 59.5% (25 cases) in digoxin groups (p < 0.001). the mean onset of action was 56.66 ± 39.52 minutes (10 180) in amiodarone receivers and 135.38 ± 110.41 minutes (25 540) in digoxin group (p < 0.001). none of the patients showed any adverse outcomes of hypotension, bradycardia, and rhythm control. conclusion: based on the findings of the present study, rapid af patients with relative contraindication for calcium channel blockers or beta-blockers who had received amiodarone experienced both higher (about 2 times) treatment success and a more rapid (about 2.5 times) response compared to those who received iv digoxin. keywords: amiodarone; digoxin; arrhythmias, cardiac; anti-arrhythmia agents; emergency department © copyright (2017) shahid beheshti university of medical sciences cite this article as: shojaee m, feizi b, miri r, etemadi j, feizi a. intravenous amiodarone versus digoxin in atrial fibrillation rate control; a clinical trial. emergency. 2017; 5(1): e29. 1. introduction a rrhythmias are the causes of 12-20% of emergency department (ed) admissions and one of the most important differential diagnoses in patients with complaint of tachycardia, syncope, or chest pain (1). atrial fibrillation (af) is the most common supraventricular tachyarrhythmia found in 1-1.5% of the population (2, 3). its prevalence rate is less than 0.5% in 40-50 year old population but reaches 515% in 80 year olds (4). in this dysrhythmia, re-entry is seen ∗corresponding author: bahareh feizi; imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989121827381, email: b_feizi57@yahoo.com in both atriums and leads to ineffective atrial contraction (5). clinical symptoms of af include vertigo, tachycardia, chest pain, and fatigue and its risk factors include valvular and coronary heart diseases, cardiomyopathy, cardiac failure, alcohol and caffeine usage, thyrotoxicosis, anxiety, pheochromocytome, emotional stress, hypoxia, and etc. (5, 6). calcium channel blockers and beta-blockers are the first line of treatment for this type of dysrhythmia in stable conditions. digoxin is the second line due to limitations of using first line options in critically ill patients and elderly, and in presence of hypotension, kidney disorder, and heart failure (7). in addition, iv amiodarone has been used to safely restore the sinus rhythm and control heart rate in patients with stable hemodynamics and acute atrial tachy-dysrhythmia (7). therefore, treatment varies depending on the decision of the in-charge this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. shojaee et al. 2 physician, patient condition, availability of the drug, and the treatment protocol of the hospital. based on the abovementioned points, the present study was designed aiming to compare iv digoxin and amiodarone in controlling the heart rate of patients presenting to ed with rapid ventricular response af (rapid af) and relative contraindication for first line drugs in this regard. 2. methods 2.1. study design and setting in the present clinical trial, patients presented to the ed of imam hossein, and shohadaye tajrish hospitals, tehran, iran, with rapid af and relative contraindication for calcium channel blockers and beta-blockers were treated with either iv amiodarone or iv digoxin and compared regarding success rate and complication. the study was approved by the ethics committee of shahid beheshti university of medical sciences and registered on iranian registry of clinical trials (irct) under the number irct201206047449n2. all patients filled informed consent forms before being included in the study. researchers adhered to all recommendations of helsinki protocol and confidentiality of patient information. 2.2. participants rapid af patients aged between 18 and 80 years old, with stable vital signs, and any relative contraindication for first line treatments were included. diagnosis of dysrhythmia was made based on 12-lead electrocardiogram by in-charge emergency physician and confirmed by a cardiologist. patients with unstable hemodynamics, chest pain or shortness of breath, heart failure, and unconfirmed dysrhythmia, as well as those who had a history of allergy to the drug, underlying kidney or liver diseases, or had used anti-arrhythmic agents in the past 12 hours, were excluded. documented or highly suspected evidence of heart failure and using either calcium channel blockers or beta-blockers were considered as the relative contraindications for first line treatment options. in addition, those who did not give their consent for participation in the study were not included. since all patients would be under supervision for at least 12 hours after receiving the drug, those who did not want to stay in the hospital for that long were also excluded. 2.3. intervention: using block randomization, the included patients were randomly assigned to either iv amiodarone (razi company, iran) or iv digoxin (razi company, iran) group. to homogenize the groups regarding af history, classified randomization was used. the amiodarone group patients were treated with 150 mg amiodarone diluted in 100 cc 5% dextrose water, intravenously infused during 10 minutes. in case of no improvement, another 150 mg dose was infused and all patients received a maintenance dose of 50 mg per hour during first 3 hours of treatment. for decreasing the probability of rhythm control, amiodarone was used with half the dose needed for rhythm conversion (150 mg instead of 300 mg). the other group was treated with 1 mg iv digoxin with initial injection of 0.5 mg and then two 0.25 mg doses in the second and fourth hour after intervention. the aim of treatment was control of heart rate and decreasing it to 80-100 beats per minute. heart rate not being controlled with the mentioned doses was defined as treatment failure. all patients were under constant cardiac, respiratory, and vital signs monitoring. due to differences in drug administration, follow-up and side effects between the two groups, the study could not be performed in a complete double-blind manner. yet, drug administration, treatment evaluation, and data analysis were done by 3 separate people and the patients were blind to treatment. in this study, a heart rate over 110 per minute was defined as a rapid ventricular response. 2.4. data gathering for all the studied patients a checklist consisting of demographic data (age, sex), history of digoxin consumption, time to treatment, presenting signs and symptoms, history of af, and treatment outcomes (heart rate control and probable adverse outcome) was filled. reduction of heart rate to less than 60 beats per minute, more than 20 mmhg drop in systolic blood pressure, and rhythm control were considered as adverse outcomes. data gathering was done by a senior emergency medicine resident. 2.5. statistical analysis based on previous studies, treatment success was 31 3. results 3.1. baseline characteristics 84 patients were randomly allocated to either amiodarone or digoxin treatment groups of 42 (53.6% male). the mean age of the studied patients was 61.8 ± 11.14 years (38 79). table 1 shows the baseline characteristics of the patients. no significant difference was present regarding underlying diseases (p = 0.616), history of digoxin consumption (p = 0.641) and type of presentation on admission to ed (p = 0.189). 3.2. outcome the rate of treatment failure was 21.4% (9 cases) in amiodarone and 59.5% (25 cases) in digoxin groups (p < 0.001). the mean onset of action was 56.66 ± 39.52 minutes (10 180) in amiodarone receivers and 135.38 ± 110.41 minutes (25 540) in digoxin group (p < 0.001). none of the patients showed any adverse outcomes of hypotension, bradycardia, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e29 table 1: baseline characteristics of the studied patients variable amiodarone digoxin p age (years) 63.73 ± 11.06 59.88 ± 11.02 0.113 sex male 23 (54.76) 22 (52.38) 0.50 female 19 (45.23) 20 (47.61) presenting sign and symptom dyspnea 20 (47.6) 14 (33.3) chest pain 13 (30.9) 9 (21.4) palpitation 16 (38.1) 12 (28.5) 0.189 dizziness 1 (2.3) 2 (4.7) others 2 (4.7) 10 (23.8) history of digoxin consumption yes 30 (71.4) 27 (64.3) 0.641 no 12 (28.6) 15 (35.7) data were presented as mean ± standard deviation or frequency and percentage. and rhythm control. 4. discussion based on the findings of the present study, rapid af patients with relative contraindication for calcium channel blockers or beta-blockers who had received amiodarone experienced both higher (about 2 times) treatment success and a more rapid (about 2.5 times) response compared to those who received iv digoxin. currently, controlling heart rate is deemed more important than rhythm control in treating af patients, especially in old people with non-acute symptoms (1). in 2008 kirsten et al. discovered that the results of rate and rhythm control do not show significant difference regarding cardiovascular side effects, and prevalence of mortality, cardiac arrest, and cardiac failure (9). the effect of iv amiodarone in controlling the rate has been proved in most conditions such as cardiomyopathy and coronary artery and valvular diseases (2). cochrane et al. compared the effects of amiodarone and digoxin in patients after cardiac surgery and found that administration of amiodarone as iv infusion after cardiac surgery is safe and as effective as digoxin, and decrease in rate is more obvious in amiodarone treated patients (2). in a study by del arco et al. in 2005, controlling the rate of the patients with amiodarone was more effective than digoxin (10). in our study also, response to treatment was higher in amiodarone treated group compared to digoxin group and treatment failure risk in amiodarone group was about half the digoxin group. treatment failure in atrial tachy-dysrhythmia patients may have different reasons. some believe that increase in sympathetic tone of the patients is the reason for not responding to some antiarrhythmia drugs (7). in heny et al. study, digoxin was ineffective in patients with increased sympathetic tone. in contrast, iv amiodarone was very effective and had high hemodynamic stability in critically ill patients (7). iv amiodarone has the ability to block calcium and sodium channels in addition to anti-androgenic characteristics. its anti-androgenic characteristics increase due to its ability to decrease norepinephrine, and can therefore be more effective in cases of increased sympathetic tone. based on the afore-mentioned points, it seems that between amiodarone and iv digoxin, amiodarone is a better choice for controlling the rate of af patients who had relative contraindication for first line drugs of choice, in emergency settings. yet, generalization of the findings has some limitations due to inability to double blind the study and small sample size. 5. conclusion based on the findings of the present study, rapid af patients with relative contraindication for calcium channel blockers or beta-blockers who had received amiodarone experienced both higher (about 2 times) treatment success and a more rapid (about 2.5 times) response compared to those who received iv digoxin. references 1. stellbrink c. what an emergency physician needs to know about acute care of cardiac arrhythmias. journal of emergencies, trauma and shock. 2010;3(2):126. 2. cochrane a, siddins m, rosenfeldt f, salamonsen r, mcconaghy l, marasco s, et al. a comparison of amiodarone and digoxin for treatment of supraventricular arrhythmias after cardiac surgery. european journal of cardio-thoracic surgery. 1994;8(4):194-8. 3. lip gy, kakar p, watson t. atrial fibrillationâăťthe growing epidemic. heart. 2007;93(5):542. 4. camm aj, kirchhof p, lip gy, schotten u, savelieva i, ernst s, et al. guidelines for the management of atrial fibrillation: the task force for the management of atrial this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. shojaee et al. 4 fibrillation of the european society of cardiology (esc). european heart journal. 2010;31(19):2369-429. 5. jung f, dimarco jp. treatment strategies for atrial fibrillation. the american journal of medicine. 1998;104(3):27286. 6. kowey pr, marinchak ra, rials sj, filart ra. acute treatment of atrial fibrillation. the american journal of cardiology. 1998;81(5):16c-22c. 7. heny f, clomo m, phd mark a. intraverous amiodarone for acute heart rate control in the critically ill patient with atrial tachyarhythmias. j am cardiol. 1998;81(3):594-8. 8. cowan jc, gardiner p, reid ds, newell dj, campbell rwf. a comparison of amiodarone and digoxin in the treatment of atrial fibrillation complicating suspected acute myocardial infarction. journal of cardiovascular pharmacology. 1986;8(2):252-6. 9. roy d, talajic m, nattel s, wyse dg, dorian p, lee kl, et al. rhythm control versus rate control for atrial fibrillation and heart failure. new england journal of medicine. 2008;358(25):2667-77. 10. del arco c, martin a, laguna p, gargantilla p, group iitsafiems. analysis of current management of atrial fibrillation in the acute setting: gefaur-1 study. annals of emergency medicine. 2005;46(5):424-30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion references emergency. 2017; 5 (1): e23 or i g i n a l re s e a rc h mushroom poisoning in the northeast of iran; a retrospective 6-year epidemiologic study bita dadpour1, shahrad tajoddini2, maliheh rajabi3, reza afshari4∗ 1. addiction research center, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. neuroscience research center, institute of neuropharmacology, kerman university of medical sciences, kerman, iran. 3. medical toxicology research centre, school of medicine, mashhad university of medical sciences, mashhad, iran. 4. environmental health services, bc centre for disease control, vancouver, canada. received: july 2016; accepted: august 2016; published online: 10 january 2017 abstract: introduction: toxic mushrooms are distributed across the globe with over 5000 species. among them, 100 species are responsible for most of the cases of mushroom poisoning. this study aimed to evaluate the epidemiologic pattern of mushroom poisoning among patients referred to the main toxicology center of mashhad province located in north-east of iran. methods: this cross-sectional study was conducted on patients with final diagnosis of mushroom poisoning referred to the toxicology center of mashhad, iran, from february 2005 to 2011. patients’ demographic characteristics, clinical presentations, laboratory findings, outcomes, and therapeutic measures were collected using a predesigned checklist and searching patient’s profile. results: 32 cases with the mean age of 24.6 ± 16.7 years were presented to the toxicology center following mushroom poisoning (59% female). mushroom poisoning accounted for 0.1% of all admitted cases. the mean time elapsed from consumption to referral to poisoning department was 61.9 ± 49.4 hours. 19 (59%) cases were discharged with complete recovery, 7 (22%) expired, and 6 (19%) cases left hospital against medical advice. mushroom poisoning mortality accounted for 1.5% of deceased cases in the studied center. there was significant relationship between mortality rate and higher values of inr (p = 0.035), pt (p = 0.011) and ptt (p = 0.003). likewise, there was significant relationship between the need for mechanical ventilation and higher values of inr (p = 0.035), pt (p = 0.006) and ptt (p = 0.014). the relationships between the need for icu admission, mechanical ventilation, and mortality rate with the rise of hepatic transaminases and serum bilirubin were not significant. conclusion: based on the findings, the prevalence of mushroom poisoning among patients referred to mashhad toxicology center was very low (0.1%), but with a high mortality rate of 22%. nausea and vomiting were the most common early symptoms of intoxication and higher values of coagulation profile were correlated with poor outcome. keywords: mushroom poisoning; epidemiology; mortality; toxicology; iran © copyright (2017) shahid beheshti university of medical sciences cite this article as: dadpour b, tajoddini sh, rajabi m, afshari r. mushroom poisoning in the northeast of iran; a retrospective 6-year epidemiologic study. emergency. 2017; 5 (1): e23. 1. introduction the clinical picture caused by poisonous compounds in mushrooms is called mushroom poisoning or "mycetismus"(1). toxic mushrooms are distributed across the globe with over 5000 species. among them, 100 species are responsible for most of the cases of mushroom poisoning ∗corresponding author: reza afshari; addiction research centre, mashhad university of medical science, imam reza hospital, ibn-e-sina street. email: afsharir@mums.ac.ir tel: 00989133983682 (2). mushroom poisoning is responsible for 50 to 100 deaths per year in western europe. the frequency of mushroom poisoning is less common in the united states (2). lethal dose of alpha-amanitin is reported to be 0.1 mg/kg. a single specimen of amanita phalloides may contain more than enough of this constituent to kill a man (3). the time interval between the ingestion of the mushrooms and the appearance of first symptoms is important for prognosis (1). this latency period is assessed as an independent prognostic factor (4). exposures with late clinical manifestation are more toxic. mushrooms with short incubation period (usually less than 6 hours) contain muscarine, coprin, ibotenic acid this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. dadpour et al. 2 and psilocybin toxins in which clinical manifestation is mild and symptoms resolve in shorter period of time (1). clinical manifestations following ingestion of toxic mushrooms are primarily gastrointestinal, which in some cases lead to hepatic, renal and nervous system damage and even death after a transient improvement phase (5). the amatoxin is responsible for gastrointestinal symptoms as well as hepatic and renal failure (6). hepatotoxic mushroom poisoning (due to amanita, lepiota and galerina species) should be considered as a medical emergency, since an early diagnosis and immediate treatment are required for a successful outcome (5). this study aimed to evaluate the epidemiologic pattern of mushroom poisoning among patients referred to the main toxicology center of mashhad province in north-east of iran. 2. methods 2.1. study design this retrospective cross-sectional study was designed to evaluate the epidemiologic pattern of mushroom poisoning among patients referred to the toxicology center of mashhad, khorasan razavi province, iran, from february 2005 to 2011. all cases of intoxication in this province are referred to the studied center. the protocol of the study was approved by the ethic committee of mashhad university of medical sciences and researchers adhered strictly to the helsinki declarations and confidentiality of patients’ information. 2.2. participants all patients with final diagnosis of mushroom poisoning were enrolled using census sampling and without any sex or age limitation. diagnosis was made based on history, clinical manifestation and epidemiologic data. no specific diagnostic laboratory tests were applied, as there were not available. latency period was defined as the time duration between the consumption of mushrooms and initiation of earliest gastrointestinal symptoms. 2.3. data gathering patients’ demographic characteristics (sex, age, latency period, etc.), clinical presentations, laboratory findings (liver enzyme, coagulation profile, and bilirubin), outcome (death, discharge, need for intensive care unit (icu) admission, and mechanical ventilation), and therapeutic measures (activated charcoal, fluids, penicillin g, and silymarin) were collected using a predesigned checklist and searching patient’s profile. a trained toxicology resident was responsible for abstraction of data from patient’s profile. 2.4. statistical analysis spss (statistical package for social sciences) version 11.5 was used for statistical analysis. data were reported as mean and standard deviation or frequency and percentage. relationship between mortality rate and level of laboratory measures was calculated using chi-square or fisher’s exact tests. a pvalue of less than 0.05 was considered significant. 3. results: 3.1. demographic during the study period, 32 cases with the mean age of 24.6 ± 16.7 (range: 6 73) years were presented to ed following mushroom poisoning (59% female, 62% resided in suburbs). mushroom poisoning accounted for 0.1% of all admitted cases in the studied center. the mean time elapsed from consumption to referral to poisoning department was 61.9 ± 49.4 (range: 9 168) hours. table 1 shows the frequency of patients’ sign and symptom at the admission time. the mean value of first recorded laboratory measures were as follows: aspartate aminotransferase (ast) 434 ± 947 (15 3812) iu/l, alanine aminotransferase (alt) 534 ± 972 (10 3426) iu/l, total bilirubin 4.0 ± 6.3 (0.3 27.9) mg/dl, direct bilirubin 1.7 ± 2.5 (0.1 9.3) mg/dl, prothrombin time (pt) 24.6 ± 24.6 (11.9 121.0) seconds, partial thromboplastin time (ptt) 33.8 ± 12.5 (19.3 72.6) seconds, and international normalized ratio (inr) 2.5 ± 3.6 (0.9 -15.0). 3.2. treatment penicillin g (1million units/kg/day) and silymarin (25-50 mg/kg/day) were administered for 69% and 72% of poisoned cases, respectively. 25% of patients received activated charcoal and sorbitol prior to admission to the toxicology center. 3.3. outcome 19 (59%) cases were discharged with complete recovery, 7 (22%) expired, and 6 (19%) cases left hospital against medical advice. mushroom poisoning mortality accounted for 1.5% of deceased cases in the studied center. there was significant relationship between mortality rate and higher values of inr (p = 0.035), pt (p = 0.011) and ptt (p = 0.003). likewise, there was significant relationship between the need for mechanical ventilation and higher values of inr (p = 0.035), pt (p = 0.006) table 1: frequency of patients’ sign and symptom at the admission time complaint number (%) nausea 28 (88) vomiting 24 (76) vertigo 16 (50) loss of consciousness 7 (22) epigastric pain 4 (13) convulsion 2 (6) icter 4 (13) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e23 and ptt (p = 0.014). there was significant relationship between the need for icu admission and higher values of inr (p< 0.001). the relationships between the need for icu admission, mechanical ventilation, and mortality rate with rise of hepatic transaminases and serum bilirubin were not significant. 4. discussion: based on the results of the present study, the prevalence of mushroom poisoning among patients referred to the main toxicology center of mashhad province located in north east of iran was very low (0.1%), but with a high mortality rate of 22%. nausea and vomiting were the most common early symptoms of intoxication and higher values of coagulation profile were correlated with poor outcome. nearly 10,000 species of mushrooms are identified in the world and approximately 50-100 species are considered as poisonous (7). about 90% of mushrooms that involved in exposures could not be identified (8). amanita species (including a. phaloids, a. virosa and a. verna) , gyromitra esculenta, and the galerina species are three most common poisonous mushrooms (9). amanita grows in many forest cover areas in iran such as mazandaran, gilan and azarbaijan (forest arasbaran) and is the most dangerous toxic mushroom in iran and worldwide (10). mushroom poisoning was less frequent in our study in comparison to a study conducted in turkey (2). the casefatality rate, however, was higher. in turkish study just 12 out of 143 patients died due to fulminant hepatic failure. even lower mortality rate was reported from texas (11).in contrast, much higher mortality rate has been observed from plovdiv region of bulgaria (12). this difference could be attributed to variation of mushroom species, different amount of ingested amatoxin or even individual susceptibility (1). case finding could also be limited in some areas. higher case-fatality rate in this study could be related to limited case reporting capabilities where just more dramatic cases are being referred. despite widespread application of some empiric treatments including non fda approved penicillin g, silymarin, no definite treatment has been introduced for mushroom poisoning to date (13). in this study, nonspecific antidotes including penicillin g, silymarin were administered in majority of cases in addition to conservative treatments. penicillin g displaces amanitin from the binding to plasma protein and thus promoting its excretion and preventing its hepatic uptake and also enhances the elimination of the toxin from the kidneys (14). although most mushroom poisonings are presented with gastrointestinal symptoms alone and cases are usually discharged with recovery, but liver function impairment could happen in some cases and may lead to life threatening consequences (15). taking the need for mechanical ventilation, or icu admission and death as determinants for poor prognosis in mushroom poisoning, impairment of coagulation tests (pt, ptt and inr) represented poor outcome in this study whereas increased transaminases (ast and alt) played no role in prognosis, even though they increased to more than 10 fold of normal limits. therefore, ordering of early and serial coagulation tests is recommended. considering high mortality rate, all patients with the history of mushroom ingestion should be admitted; accordingly treated and followed up (16). alpha amanitin levels should be checked where possible, if amanita poisoning is suspected. if laboratory detection of toxin is not available, history of mushroom ingestion, clinical manifestation and their trends could define mushroom poisoning (17). 5. limitations: as a retrospective investigation, we were required to extract information from medical records and some necessary data were not recorded properly. 6. conclusion: based on the results of the present study, the prevalence of mushroom poisoning among patients referred to the main toxicology center of mashhad was very low (0.1%), but with a high mortality rate of 22%. nausea and vomiting were the most common early symptoms of intoxication and higher values of coagulation profile were correlated with poor outcome. 7. appendix 7.1. acknowledgements we would like to thank the personnel of medical records department and in particular mrs. hoseini for their kind cooperation. kind support of vice chancellor for research, mashhad university of medical sciences, is also acknowledged. 7.2. authors contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the 4 criteria of authorship recommended by the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. dadpour et al. 4 references 1. erguven m, yilmaz o, deveci m, aksu n, dursun f, pelit m, et al. mushroom poisoning. indian journal of pediatrics. 2007;74(9):847-52. 2. yardan t, baydin a, eden ao, akdemir hu, aygun d, acar e, et al. wild mushroom poisonings in the middle black sea region in turkey: analyses of 6 years. human and experimental toxicology. 2010;29(9):767-71. 3. bergis d, friedrich-rust m, zeuzem s, betz c, sarrazin c, bojunga j. treatment of amanita phalloides intoxication by fractionated plasma separation and adsorption (prometheus). j gastrointestin liver dis. 2012;21(2):1716. 4. ganzert m, felgenhauer n, schuster t, eyer f, gourdin c, zilker t. 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[acute mushrooms poisoning]. revista clinica espanola. 2009;209(11):542-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e36 or i g i n a l re s e a rc h curb-65, qsofa, and sirs criteria in predicting inhospital mortality of critically ill covid-19 patients; a prognostic accuracy study sorour khari1, atefe salimi akin abadi2, marzieh pazokian3∗, mahmoud yousefifard4 † 1. student research committee, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. clinical research development center, shahid modarres educational hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of medicalsurgical nursing, school of nursing and midwifery, clinical research development center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 4. physiology research center, iran university of medical sciences, tehran, iran. received: march 2022; accepted: april 2022; published online: 10 may 2022 abstract: introduction: outcome prediction of intensive care unit (icu)-admitted patients is one of the important issues for physicians. this study aimed to compare the accuracy of quick sequential organ failure assessment (qsofa), confusion, urea, respiratory rate, blood pressure and age above or below 65 years (curb-65), and systemic inflammatory response syndrome (sirs) scores in predicting the in-hospital mortality of covid-19 patients. methods: this prognostic accuracy study was performed on 225 icu-admitted patients with a definitive diagnosis of covid-19 from july to december 2021 in tehran, iran. the patients’ clinical characteristics were evaluated at the time of icu admission, and they were followed up until discharge from icu. the screening performance characteristics of curb-65, qsofa, and sirs in predicting their mortality was compared. results: 225 patients with the mean age of 63.27±14.89 years were studied (56.89% male). the in-hospital mortality rate of this series of patients was 39.10%. the area under the curve (auc) of sirs, curb-65, and qsofa were 0.62 (95% ci: 0.55 0.69), 0.66 (95% ci: 0.59 0.73), and 0.61(95% ci: 0.54 0.67), respectively (p = 0.508). in cut-off ≥1, the estimated sensitivity values of sirs, curb-65, and qsofa were 85.23%, 96.59%, and 78.41%, respectively. the estimated specificity of scores were 34.31%, 6.57%, and 38.69%, respectively. in cut-off ≥2, the sensitivity values of sirs, curb-65, and qsofa were evaluated as 39.77%, 87.50%, and 15.91%, respectively. meanwhile, the specificity of scores were 72.99%, 34.31%, and 92.70%. conclusion: it seems that the performance of sirs, curb-65, and qsofa is similar in predicting the icu mortality of covid-19 patients. however, the sensitivity of curb-65 is higher than qsofa and sirs. keywords: systemic inflammatory response syndrome; organ dysfunction scores; clinical decision rules; intensive care units; mortality; covid-19 cite this article as: khari s, pazokian m, salimi akin abadi a, abadi a, yousefifard m. curb-65, qsofa, and sirs criteria in predicting in-hospital mortality of critically ill covid-19 patients; a prognostic accuracy study. arch acad emerg med. 2022; 10(1): e36. https://doi.org/10.22037/aaem.v10i1.1565. ∗corresponding author: marzieh pazokian; department of medicalsurgical nursing, school of nursing and midwifery, clinical research development center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. email: pazokian@sbmu.ac.ir, orcid: http://orcid.org/0000-0002-7583-1824. † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran. email: yousefifard.m@iums.ac.ir / yousefifard20@gmail.com, phone/fax: +982186704771, orcid: http://orcid.org/0000-0001-5181-4985. 1. introduction the covid-19 pandemic started as an array of acute respiratory illnesses in wuhan, china (1, 2). although most patients infected with covid-19 have minor signs, those older or with underlying diseases are more likely to have poor outcomes that progress to acute respiratory distress syndrome or multiple organ failure (3). early and rapid detection to prevent death in critically highrisk covid-19 patients depends on the effective primary dithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khari et al. 2 agnosis (4). prognostic scores can aid in clinical decisionmaking. there were several scores that international guidelines had confirmed to use for acute infectious disease before the covid-19 pandemic (5). the quick sequential organ failure assessment (qsofa) score, the confusion, urea, respiratory rate, blood pressure and age above or below 65 years (curb-65) score, and the systemic inflammatory response syndrome (sirs) criteria are examples of ordinary scoring systems assessing disease severity, utilized in management of pneumonia and sepsis patients’ condition (6). the qsofa score originated from three parameters: systolic blood pressure ≤ 100 mmhg, respiratory rate ≥ 22 breaths/min, and altered mental status (gcs<15) (4). the qsofa simplifies the risk classification in patients with covid-19 and has been broadly sued to screen patients with life-threatening conditions in hospitals (7). the curbe-65 score involves vital signs such as confusion, urea> seven mmol/l, respiratory rate≥30 breaths/min, blood pressure (systolic<90mmhg, diastolic≤60mmhg), and age ≥65, and is used to predict the 30-day mortality in adult patients with bacterial pneumonia (8, 9). sirs identifies with at least two from 4 following criteria: fever >38.0°c or hypothermia <36.0°c, tachycardia >90 beats/minute, tachypnea >20 breaths/minute, white blood cell count (<4×109/l or >12×109/l) (10). current evidence from developed countries approve of the utility of the qsofa, curb-65, and sirs for predicting the outcomes related to covid-19 patients, including the need for icu admission or mortality (8, 11-13). however, such data is limited in developing countries (14). also, very few studies are available to identify whether these scores can be used to predict covid-19 patients’ mortality in icu (14). accordingly, this study aimed to compare the screening performance of qsofa, curb-65, and sirs criteria in predicting the in-hospital mortality of icu-admitted covid-19 patients. 2. methods 2.1. study design and setting this prognostic accuracy study was conducted in the shahid modarress educational hospital in tehran, iran, from july to december 2021. the scores of qsofa, curb-65, and sirs criteria were calculated for all patients and the screening performance of models in predicting in-hospital mortality were compared. the participants were informed about the objectives, and patients or their relatives signed the informed consent forms. the study protocol was approved by the ethics committee of the clinical development unit of loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran (ir.sbmu.retech.rec.1400.193; research proposal cod:27784). 2.2. participants the study population included 225 patients with a definitive diagnosis of covid-19 infection (based on reverse transcription polymerase chain reaction (rt-pcr) technique) who were admitted to the icu. patients were selected using the convenience sampling technique. the patients were chosen according to the chest ct scan, pcr test, and doctor’s approval. inclusion criteria included patients admitted to icu due to covid-19, over 18 years old, and not pregnant. the exclusion criteria were transferring patients to other centers. 2.3. data gathering research tools included a checklist containing demographic information (age, gender), baseline variables such as underlying diseases, blood test results, vital signs, lengths of hospitalization in the icu, and discharge time. a checklist containing the parameters of qsofa, sirs, and curb-65 was used to evaluate patients on admission to the icu. the discharge status (mortality/survival) and patients’ length of stay were also specified in this checklist. accurate devices were used to measure the patient’s vital signs, such as blood pressure (hand pressure gauge), oxygen saturation level and heart rate (calibrated pulse oximeter device), and temperature (non-contact thermometer). all patients were examined on admission and followed up until discharge from the icu. the mortality status of patients in icu was considered as the outcome. the patients’ survival status at the time of discharge was recorded. 2.4. statistical analysis analyses were performed using stata 14.0 statistical software. descriptive statistics included means ± sds for quantitative variables and frequency (percentage) for qualitative variables. the independent sample t-test and fisher’s exact test were carried out to compare the variables between survivors and non-survivors. the area under the receiver operating characteristic (roc) curve (auc), sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values with 95% confidence interval were calculated and reported for scoring systems (qsofa, curbe-65, and sirs). two cut-off values for each scoring system were used. we used a pre-defined cut-off of 2 for the evaluated tools based on previous studies (5, 13, 16, 17) and a cut-off of 1 according to the receiver operating characteristic (roc) analysis of the current research. 3. results 3.1. baseline characteristics 225 patients with the mean age of 63.27±14.89 years were studied (56.89% male). table 1 shows the baseline characterthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e36 table 1: baseline characteristics of icu-admitted covid-19 patients variables all patients (n= 225) survived (n=137) died (n=88) p age (year) 63.27±14.89 58.96±14.59 69.96±12.78 <0.001 gender male 128 (56.89) 78 (56.93) 50 (56.82) 0.986 female 97 (43.11) 59 (43.07) 38 (43.18) hypertension yes 124 (55.11) 68 (49.64) 56 (63.64) 0.039 no 101 (44.89) 69 (50.36) 32 (36.36) diabetes mellitus yes 70 (31.11) 33 (24.09) 37 (42.05) <0.001 no 155 (68.89) 104 (75.91) 51 (57.95) cardiovascular disease yes 62 (27.56) 34 (24.82) 28 (31.82) 0.251 no 163 (72.44) 103 (75.18) 60 (68.18) pulmonary disease yes 13 (5.78) 7 (5.11) 6 (6.82) 0.592 no 212 (94.22) 130 (94.89) 82 (93.18) kidney disease yes 17 (7.56) 7 (5.11) 10 (11.36) 0.083 no 208 (92.44) 130 (94.89) 78 (88.64) addiction yes 4 (1.78) 3 (2.19) 1 (1.14) 0.56 no 221 (98.22) 134 (97.81) 87 (98.86) malignancy yes 14 (6.22) 8 (5.84) 6 (6.82) 0.767 no 211 (93.78) 129 (94.16) 82 (93.18) others comorbidities yes 60 (26.67) 33 (24.09) 27 (30.68) 0.275 no 165 (73.33) 104 (75.91) 61 (69.32) vital signs pulse rate (/minutes) 82.74±16.91 81.54± 15.55 84.61±18.76 0.092 respiratory rate (/minutes) 23.16±4.57 22.43±4.23 24.29±4.88 0.003 temperature (°c) 37.08±0.31 37.05±0.29 37.13±0.33 0.071 sbp (mmhg) 129.78±20.98 128.65±19.04 131.54±23.70 0.314 dbp (mmhg) 78.72±13.78 77.89±13.31 80.02±14.47 0.258 oxygen saturation (%) 87.82±6.45 89.32±6.14 85.49±6.28 <0.001 laboratory results blood urea nitrogen (mg/dl) 55± 30.83 48.97±28.10 64.40± 32.71 <0.001 wbc (109 /l) 9.15±4.96 9.05±4.61 9.30±5.47 0.709 length of stay in icu (days) mean ± sd 12.23±7.81 12±7.45 12.60±8.37 0.593 data are presents as mean ± standard deviation (sd) or frequency (%). all measures (except for length of stay) were evaluated at the time of admission to intensive care unit (icu). p-values are obtained from independent sample ttest and chi-square test. sbp: systolic blood pressure; dbp: diastolic blood pressure; wbc: white blood cell count. istics of studied cases. the in-hospital mortality rate of this series of patients was 39.10%. the mean age of survivors was significantly lower than the non-survived group (58.96±14.59 vs. 69.96±12.78 years; p < 0.001). the prevalence of hypertension (63.64 vs. 49.64%; p = 0.039) and diabetes (42.05 vs. 24.09%; p < 0.001) were significantly higher in non-survived group. the means respiratory rate (24.29 ± 4.88 vs. 22.43 ± 4.23 /minutes; p = 0.003) and blood urea nitrogen (64.40± 32.71 vs. 48.97± 28.10 mg/dl; p < 0.001) in the non-survived group were higher than in survivors, whereas the mean oxygen saturation was lower in the non-survived group (89.32 ± 6.14 vs. 85.49 ± 6.28%; p < 0.001). 3.2. accuracy of scoring systems in the prediction of icu mortality table 2 displays the screening performance characteristics of sirs, curb-65, and qsofa in predicting the in-hospital mortality of critically ill covid-19 cases. the auc of sirs, curb65, and qsofa were 0.62 (95% ci: 0.55 0.69), 0.66 (95% ci: 0.59 0.73), and 0.61(95% ci: 0.54 0.67), respectively (p = this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khari et al. 4 table 2: screening performance characteristics of studied scoring systems in predicting the in-hospital mortality of critically ill covid-9 cases score auc sensitivity specificity ppv npv plr nlr sirs ≥ 1 0.62 (0.55, 0.69) 85.23 (75.70, 91.60) 34.31 (26.55, 42.96) 45.45 (37.75, 53.37) 78.33 (65.47, 87.53) 1.29 (1.11, 1.50) 0.43 (0.25, 0.73) ≥2 39.77 (29.66, 50.78) 72.99 (64.62, 80.05) 48.61 (36.78, 60.59) 65.36 (57.20, 72.74) 1.47 (1.01, 2.14) 0.82 (0.69, 0.98) curb-65 ≥ 1 0.66 (0.59, 0.73) 96.59 (89.66, 99.11) 6.57 (3.24, 12.46) 39.91 (33.34, 46.84) 75 (42.83, 93.31) 1.03 (0.97, 1.09) 0.51 (0.13, 1.93) ≥ 2 87.50 (78.32, 93.30) 34.31 (26.55, 42.96) 46.11 (38.43, 53.96) 81.03 (68.18, 89.71) 1.33 (1.15, 1.53) 0.36 (0.20, 0.65) qsofa ≥ 1 0.61 (0.54, 0.67) 78.41 (68.10, 86.18) 38.69 (30.60, 47.41) 45.10 (37.12, 53.32) 73.61 (61.68, 82.98) 1.27 (1.07, 1.51) 0.55 (0.36, 0.85) ≥ 2 15.91 (9.28, 25.60) 92.70 (86.64, 96.25) 58.33 (36.94, 77.20) 63.18 (56.10, 69.78) 2.17 (1.01, 4.68) 0.90 (0.82, 0.99) all measures are presented with 95% confidence interval; ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; sirs: systemic inflammatory response syndrome; curb-65: confusion, urea, respiratory rate, blood pressure and age above or below 65 years; qsofa: quick sequential organ failure assessment. figure 1: comparison of the area under the receiver operating characteristic (roc) curve of sirs, curb-65, and q sofa in predicting the inhospital mortality of intensive care unit-admitted covid19 patients (p = 0.508). sirs: systemic inflammatory response syndrome; curb-65: confusion, urea, respiratory rate, blood pressure and age above or below 65 years; qsofa: quick sequential organ failure assessment. 0.508; figure1). in cut-off ≥1, the estimated sensitivity values of sirs, curb-65, and qsofa were 85.23%, 96.59%, and 78.41%, respectively. the estimated specificity of scores were 34.31%, 6.57%, and 38.69%, respectively. in cut-off ≥2, the sensitivity values of sirs, curb-65, and qsofa were 39.77%, 87.50%, and 15.91%, respectively. meanwhile, the specificity of scores were 72.99%, 34.31%, and 92.70%. 4. discussion we calculated the roc curve results based on two cut-off values. the first cut-off (≥1) was obtained from our data, and the second one (≥2) was evaluated according to previous similar studies. the results of roc curves indicated that the performance of the three assessed scoring systems had the same pattern. in cut-off≥1, the sensitivity value of curb-65 (96.59%) was higher than sirs (85.23%) and qsofa (78.41%). also, in cut-off≥2, the same results were observed; the sensitivity value of curb-65 (87.50%) was higher than sirs (39.77%) and qsofa (15.91%). curb-65 is a clinical prediction rule intended to stratify pneumonia patients by expected mortality and has a major advantage in its simplicity (18). also, the curb-65 scores are an impressive example of the value of a simple clinical approach not requiring sophisticated biochemical, immunological, or genetic data in the risk stratification of patients with an acute, potentially life-threatening condition (19). most of the studies related to covid-19 showed that curb-65 has good performance in predicting mortality in covid-19 patients (18, 19). according to our search, the only similar study was conducted in india to predict the mortality of 140 covid-19 patients in icu. the study illustrated that the news2, sirs, qsofa, and curb-65 were calculated prospectively, and the curb-65 (auc: 0.72) had better performance in predicting icu mortality compared to qsofa (auc: 0.63) and sirs (auc: 0.54) (14). in a multicenter prospective study with 830 adult patients with covid-19, the prognostic scores, including curb-65, news2, and qsofa, were compared. the auc values of curb-65 and qsofa for icu admission were 0.63 and 0.56, respectively. also, in the low-risk levels (curb-65 score <2 and qsofa score<2), the mortality rates were 16.7% and 21.4%, respectively (5). in line with the results of this study, there were several studies with covid-19 patients that confirmed the same results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e36 the auc values of qsofa were 0.56, 0.55, 0.69, and 0.78, indicating its inferior performance compared with other scoring systems (13, 20-22). also, the auc values of curb-65 and sirs were 0.76 and 0.74, indicating their lower performance than news (13, 22). on the other hand, in a recent retrospective cohort study with 247 covid-19 patients admitted to icu, the efficiency of curb-65 in predicting 30-day mortality was assessed, and the findings indicated that among patients hospitalized with covid-19 those with curb-65≥ 2 had a higher risk of 30-day mortality (8). although one of the advantages of the qsofa score is its simplicity and speed of application, several studies showed that the qsofa score had a low sensitivity for in-hospital mortality of patients with suspected infection (4). also, the results of a retrospective study with 140 severely ill covid-19 patients illustrated that the area under the roc curve for sofa (0.89) was significantly higher than qsofa (0.74). thus, the performance of sofa was superior to that of qsofa (4). and also, an observational retrospective study with 237 adults hospitalized with covid-19 was performed to compare the application of sofa, qsofa, and news. their results displayed that the auc value of qsofa was found to be 0.72 (cut-off ≥1) for in-hospital mortality outcomes and had an infirm performance compared to other scores. however, they noted that sepsis scores were of value for predicting respiratory failure and mortality in covid-19 patients (11). however, only one study showed that performance of q-sofa in covid-19 patients was better than sirs and curb-65. this retrospective cohort study with 235 elderly adults was conducted to compare the seven scoring systems in predicting the mortality rate. the results showed that the auc of sirs, curb-65, and qsofa were 0.69, 0.85, and 0.88, respectively (6). 5. limitations the small sample size and the lack of long-term follow-up for the survived patients after icu discharge are among the limitations of the present study. 6. conclusion the present study showed that the auc 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in patients admitted with community-acquired pneumonia. ann emerg med. 2019;74(1):60-8. 19. shah ba, ahmed w, dhobi gn, shah nn, khursheed sq, haq i. validity of pneumonia severity index and curb-65 severity scoring systems in community acquired pneumonia in an indian setting. indian j chest dis allied sci. 2010;52(1):9. 20. covino m, sandroni c, santoro m, sabia l, simeoni b, bocci mg, et al. predicting intensive care unit admission and death for covid-19 patients in the emergency department using early warning scores. resuscitation. 2020;156:84-91. 21. saberian p, tavakoli n, hasani-sharamin p, modabber m, jamshididana m, baratloo a. accuracy of the pre-hospital triage tools (qsofa, news, and presep) in predicting probable covid-19 patients’ outcomes transferred by emergency medical services. caspian j intern med. 2020;11(suppl 1):536. 22. liu f-y, sun x-l, zhang y, ge l, wang j, liang x, et al. evaluation of the risk prediction tools for patients with coronavirus disease 2019 in wuhan, china: a singlecentered, retrospective, observational study. crit care med. 2020;48(11):e1004-e1011. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e5 or i g i n a l re s e a rc h 20-day trend of serum potassium changes in bam earthquake victims with crush syndrome; a cross-sectional study saeed safari1, iraj najafi2∗, mostafa hosseini3, alireza baratloo 1, mahmoud yousefifard4, hamidreza mohammadi1 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of nephrology, dr. shariati hospital, tehran university of medical sciences, tehran, iran. 3. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 4. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. received: february 2016; accepted: april 2016; published online: 8 january 2017 abstract: introduction: many of those who survive following an earthquake die in the next phase due to preventable and treatable medical conditions such as hyperkalemia. the present study aimed to evaluate the trend of potassium changes in crush syndrome patients of bam earthquake. methods: in this retrospective cross-sectional study, using the database of bam earthquake victims, which were developed by iranian society of nephrology following bam earthquake, iran, 2003, the 20-day trend of potassium changes in > 15 years old crush syndrome patients was evaluated. results:135 crush syndrome patients with the mean age of 29.9 ± 9.91 years were evaluated (56.3% male). mean potassium concentration during the first 3 days of admission was 5.6 ± 1.3 meq/l. on the day of admission, 43.1% (95% ci: 34.0 52.2) had normal potassium concentration, 3.4% (95% ci: 0.1 6.8) had hypokalemia, and 53.4% (44.3 62.6) had hyperkalemia. during 20-day follow-up, 62.3% (95% ci: 66.7-71.9) of the patients had normal potassium. while, 11.5% (95% ci: 9.7-13.3) had hypokalemia and 19.2% (95% ci: 17.021.5) had hyperkalemia. as the days of hospitalization increased, prevalence of hyperkalemia decreased while hypokalemia increased. on the 17th day 21.2% (95% ci: 2.2-39.9) had hypokalemia and 10.5% (95% ci: 0.1 24.7) had hyperkalemia. conclusion: findings of the present study showed that following urine alkalinization and fluid resuscitation, the prevalence of hyperkalemia reduced, but hypokalemia developed. it seems that the correction of serum potassium level should be accompanied by precise monitoring of intake and output of the patient and prescription of reasonable amount of intravenous fluid. keywords: rhabdomyolysis; crush syndrome; potassium; water-electrolyte imbalance; disaster victims © copyright (2017) shahid beheshti university of medical sciences cite this article as: safari s, najafi i, hosseini m, baratloo a, yousefifard m, mohammadi h. 20-day trend of serum potassium changes in bam earthquake victims with crush syndrome; a cross-sectional study. emergency. 2017; 5 (1): e5. 1. introduction crush syndrome following traumatic rhabdomyolysis is a life-threatening condition that is accompanied by severe shock, cardiovascular disorders and acute kidney injury. traumatic rhabdomyolysis is a result of direct pressure ∗corresponding author: iraj najafi; department of internal medicine, dr. shariati hospital, tehran university of medical sciences, north karegar avenue, tehran 14114 iran. tel/fax: +98 21 22721155; email: najafi63800@yahoo.com. on skeletal muscles and is frequently seen in accidents, sports and most importantly in natural disasters such as earthquakes (1-3). electrolyte abnormalities are among very common problems of these patients. when pressure is removed and perfusion of ischemic body part is restored, intracellular ions are released in the systemic circulation through the damaged cell membrane (4, 5). hyperkalemia is the most important and fatal electrolyte imbalance in these patients (6). severe hyperkalemia may lead to dysrhythmia, cardiac arrest and finally sudden death. this electrolyte imbalance can occur on the site of accident, during transportation to the hospital and even during hospitalization (7). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 2 to control this condition, early and vigorous fluid resuscitation can be helpful and sometime lifesaving (8). however, there are studies that show vigorous fluid resuscitation can leads to a drop in serum potassium level and sometime hypokalemia (9). some existing studies have evaluated the changes in the ion concentration of crushed patients in the initial 3 days after earthquake (7, 10, 11). however, there is not enough knowledge regarding long-term changes in the concentration of this ion. therefore, the present study aimed to evaluate the 20-day trend of potassium concentration changes in crush syndrome patients of bam earthquake. 2. methods 2.1. study design and setting the present study is a retrospective cross-sectional one designed to evaluate the trend of changes in potassium ion during the 20 initial days of hospitalization in crush syndrome patients of bam earthquake. this study was approved by the ethics committee of shahid beheshti university of medical sciences, tehran, iran. the researchers adhered to the principles of helisinki declaration and confidentiality of patient information throughout this study. 2.2. participants to achieve the aims of this study, the data of bam earthquake victims were used. following bam earthquake, iran, 2003, iranian society of nephrology with the association of international society of nephrology, designed a questionnaire and sent it to all the hospitals that were expected to admit the earthquake victims. these hospitals included 15 centers in 7 cities of bandarabbas, bushehr, isfahan, kerman, shiraz, tehran, and zahedan. data from shiraz were not entered to the database since the centers did not cooperate. data were entered to a database in the same year. the details of data gathering and management have been introduced in previously published studies (1, 12-15). in the present study, crush syndrome patients whose serum potassium level was recorded for at least the initial 3 days of admission were included. patients under 15 years old, those with chronic kidney diseases and patients whose creatine phosphokinase (cpk) was never measured were excluded. crush syndrome was defined as traumatic rhabdomyolysis leading to serum creatinine over 1.66 mg/dl and cpk higher than 1000 iu/l in 2 measurements during hospitalization (16). hypokalemia was defined as serum potassium level lower than 3.5 meq/l and hyperkalemia as serum potassium level higher than 5 meq/l (17). serum potassium levels were evaluated daily and the data was recorded in the database. 2.3. statistical analysis considering 15.9% prevalence of hyperkalemia (10), 95% confidence interval (ci), and 0.06 accuracy, the sample size was calculated to be 134 cases. data from the database were entered to stata 11.0 and analyzed. serum potassium level was reported as mean ± standard deviation (sd). patients were classified as normal, hypokalemia and hyperkalemia based on their serum potassium level and the prevalence was reported with 95% ci. 3. results: 135 crush syndrome patients with the mean age of 29.9 ± 9.91 years were evaluated (56.3% male). demographic, clinical, and laboratory findings of the patients are presented in table 1. mean and sd of potassium concentration during the first 3 days of admission was 5.6 ± 1.3 meq/l. trend of changes of mean potassium level with 95% ci showed little variation during the first 20 days of admission (figure 1). on the day of admission, 43.1% (95% ci: 34.0 52.2) had normal potassium concentration, 3.4% (95% ci: 0.1 6.8) had hypokalemia, and 53.4% (44.3 62.6) had hyperkalemia. during 20-day follow-up, 62.3% (95% ci: 66.7-71.9) of the patients had normal potassium. while, 11.5% (95% ci: 9.7-13.3) had hypokalemia and 19.2% (95% ci: 17.0-21.5) had hyperkalemia. as the days of hospitalization increased, prevalence of hyperkalemia decreased while hypokalemia increased. on the 17th day 21.2% (95% ci: 2.2-39.9) had hypokalemia and 10.5% (95% ci: 0.1 24.7) had hyperkalemia. table 1: baseline characteristics of included patients variable values age (years) 15-34 105 (79.2) 35-54 17 (12.6) ≥55 11 (8.2) gender male 76 (56.3) female 59 (43.7) time under the rubble (hours) 6.2 ± 3.4 systolic blood pressure (mmhg) 126.8 ± 2.6 diastolic blood pressure (mmhg) 77.9 ± 1.0 fluid intake (ml) 2872.0 ± 1829.0 urine output (ml) 897.0 ± 923.0 blood urea nitrogen (mg/dl) 104.0 ± 59.0 creatinine (mg/dl) 4.73 ± 2.3 creatine phosphokinase (iu/l) 17.4 ± 24.7 lactate dehydrogenase (u/l) 3.1 ± 2.5 uric acid (mg/dl) 8.5 ± 2.8 data were presented as mean ± standard deviation or number (%). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e5 table 2: prevalence of hypokalemia, normal, and hyperkalemia among bam earthquake victims during 20 days of admission day normal hypokalemia hyperkalemia prevalence 95% ci prevalence 95% ci prevalence 95% ci 1 43.1 34.0 52.2 3.4 0.1 6.8 53.4 44.3 62.6 2 56.8 47.8 65.8 2.5 0.0 5.4 40.7 31.8 49.6 3 67.9 59.0 76.9 11.3 5.3 17.4 20.8 13.0 28.5 4 66.1 57.1 75.0 15.6 8.7 22.4 18.3 11.0 25.7 5 71.0 62.1 79.9 14.0 7.2 20.8 15.0 8.0 22.0 6 75.9 66.8 84.9 12.6 5.6 19.7 11.5 4.7 18.2 7 76.4 66.5 86.3 15.3 6.9 23.7 8.3 1.9 14.8 8 77.6 67.5 87.7 13.4 5.2 21.7 9.0 2.1 15.9 9 63.5 50.2 76.7 21.2 9.9 32.4 15.4 5.5 25.3 10 86.0 76.3 95.7 6.0 0.0 12.7 8.0 0.1 15.6 11 83.3 72.7 94.0 14.6 4.5 24.7 2.1 0.1 6.2 12 76.7 64.0 89.5 14.0 3.5 24.4 9.3 0.5 18.1 13 81.1 68.3 93.9 8.1 0.1 17.0 10.8 0.7 21.0 14 77.8 61.8 93.8 11.1 0.1 23.2 11.1 0.1 23.2 15 69.2 51.1 87.3 23.1 6.5 39.6 7.7 0.1 18.1 16 80.0 64.0 96.0 12.0 0.1 25.0 8.0 0.1 18.9 17 68.4 46.9 89.9 21.1 2.2 39.9 10.5 0.1 24.7 18 80.0 70.0 90.0 6.7 0.1 19.7 13.3 0.1 25.1 19 91.0 88.0 96.0 0.0 0.1 0.0 9.0 0.6 16.0 20 100.0 90.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 total 69.3 66.7 71.9 11.5 9.7-13.3 19.2 17.0-21.5 ci: confidence interval. at the end of the 20th day, all cases of hypo and hyperkalemia were corrected (table 2 and figure 2). 4. discussion: findings of the present study showed the 53.4% prevalence of hyperkalemia and 3.4% hypokalemia in crush syndrome patients of bam earthquake victims on the day of admission. following therapeutic interventions, urine alkalinization figure 1: mean and 95% confidence interval of potassium levels during first 20 days after crush injury. and fluid resuscitation, the prevalence of hyperkalemia decreased but hypokalemia increased. clinical and laboratory variables monitoring in the earthquake victims can be helpful in rapid diagnosis and efficient management of these patients (18-22). the frequent cause of mortality at the scene of disaster is direct trauma. however, many of those who survive die in the next phase due to preventable and treatable medical conditions such as hyperkalemia. hyperkalemia is the most important electrolyte that can lead figure 2: trend of hyperkalemia and hypokalemia prevalence among studied patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 4 to a higher rate of mortality by causing fatal arrhythmias (7, 10, 11, 23, 24). a study by sever et al. on crush syndrome patients after marmara earthquake in turkey showed that hyperkalemia is the most important life-threatening problem in patients with traumatic crush syndrome (25). studying the causes of mortality in crush syndrome patients in marmara earthquake in turkey showed that 42% of the cases that died due to crush syndrome had hyperkalemia (7). oda et al. analyzed data of those who were injured in hanshin-awaji earthquake in japan and introduced hyperkalemia as one of the most important causes of death among patients with crush syndrome (11). however, data of wenchuan earthquake in china show that hypokalemia (18.2%) was more common than hyperkalemia (15.9%). researchers believe that this has happened since most of those with hyperkalemia have died on the way to hospital as there was not enough fluid for early fluid resuscitation on the scene in wenchuan earthquake (10). however, hypokalemia is a problem that has not been studied properly. early and vigorous fluid resuscitation can prevent acute kidney injury in earthquake victims with crush syndrome. in addition, it can reduce the severity of hyperkalemia and prevent it from leading to fatal arrhythmias (9). for instance, gunal et al. studied 15 victims of bingol earthquake and showed that on admission, 9 had hypokalemia, while only one had hyperkalemia. these researchers believe this to be due to fluid resuscitation and bicarbonate prescription on the scene (9). in bam earthquake, lack of enough fluid for fluid resuscitation on the scene led to lack of fluid resuscitation during the initial hours of the incident for many of the victims. therefore, hyperkalemia was very common on the first day. however, during the course of hospitalization fluid resuscitation reduced the prevalence of hyperkalemia. yet, too much fluid resuscitation led to hypokalemia. although all cases of hypo and hyperkalemia were resolved on the 20th day, since hypokalemia may be accompanied by the probability of cardiotoxicity, precise monitoring of intake and output of the patient and prescription of reasonable amounts of intravenous fluid can be important in correcting this imbalance and preventing it. excessive fluid resuscitation during hospitalization can be prevented by adjusting fluid resuscitation based on laboratory findings and serum ion levels of the patients. 5. limitation: missing data, outdated data, referring the victims to different health centers, different therapeutic and resuscitative approaches, variations in management of the patient in these centers, and not exactly knowing the type of trauma and its severity are among the most important limitations of this study. despite all these limitations, since our information regarding management and outcome of patients with crush syndrome is limited, the authors decided to study and publish the minimum existing data. 6. conclusion: findings of the present study showed that following urine alkalinization and fluid resuscitation, the prevalence of hyperkalemia reduced, but hypokalemia developed. it seems that correction of serum potassium level should be accompanied by precise monitoring of intake and output of the patient and prescription of reasonable amount of intravenous fluid. 7. appendix 7.1. acknowledgements this article has been extracted from dr. hamidreza mohammadi’s thesis for achieving his md degree from the faculty of medicine at shahid beheshti university of medical sciences. 7.2. conflict of interest none. 7.3. funding support none declared. 7.4. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. hosseini m, safari s, sharifi a, amini m, farokhi fr, sanadgol h, et al. wide spectrum of traumatic rhabdomyolysis in earthquake victims. acta med iran. 2009;47(6):459-64. 2. najafi i, van biesen w, sharifi a, hoseini m, farokhi fr, sanadgol h, et al. early detection of patients at high risk for acute kidney injury during disasters: development of a scoring system based on the bam earthquake experience. j nephrol. 2008;21(5):776-82. 3. tolouian r, wild d, lashkari mh, najafi i. oral alkalinizing solution as a potential prophylaxis against myoglobinuric acute renal failure: preliminary data from healthy volunteers. nephrol dial transplant. 2005;20(6):1228-31. 4. gonzalez d. crush syndrome. crit care med. 2005;33(1):s34-41. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e5 5. huerta-alardin al, varon j, marik pe. bench-to-bedside review: rhabdomyolysis–an overview for clinicians. crit care. 2005;9(2):158-69. 6. smith j, greaves i. crush injury and crush syndrome: a review. j trauma. 2003;54(5 suppl):s226-30. 7. erek e, sever ms, serdengecti k, vanholder r, akoglu e, yavuz m, et al. an overview of morbidity and mortality in patients with acute renal failure due to crush syndrome: the marmara earthquake experience. nephrol dial transplant. 2002;17(1):33-40. 8. vanholder r, van der tol a, de smet m, hoste e, koc m, hussain a, et al. earthquakes and crush syndrome casualties: lessons learned from the kashmir disaster. kidney int. 2007;71(1):17-23. 9. gunal ai, celiker h, dogukan a, ozalp g, kirciman e, simsekli h, et al. early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes. j am soc nephrol. 2004;15(7):18627. 10. he q, wang f, li g, chen x, liao c, zou y, et al. crush syndrome and acute kidney injury in the wenchuan earthquake. j trauma acute care surg. 2011;70(5):1213-8. 11. oda j, tanaka h, yoshioka t, iwai a, yamamura h, ishikawa k, et al. analysis of 372 patients with crush syndrome caused by the hanshin-awaji earthquake. j trauma acute care surg. 1997;42(3):470-6. 12. alavi-moghaddam m, safari s, najafi i, hosseini m. accuracy of urine dipstick in the detection of patients at risk for crush-induced rhabdomyolysis and acute kidney injury. eur j emerg med. 2012;19(5):329-32. 13. safari s, najafi i, hosseini m. outcomes of fasciotomy in patients with crush-induced acute kidney injury after bam earthquake. iran j kidney dis. 2011;5(1):25-8. 14. iraj n, saeed s, mostafa h, houshang s, ali s, farin rf, et al. prophylactic fluid therapy in crushed victims of bam earthquake. am j emerg med. 2011;29(7):738-42. 15. najafi i, safari s, sharifi a, sanadgol h, hosseini m, rashid-farokhi f, et al. practical strategies to reduce morbidity and mortality of natural catastrophes: a retrospective study based on bam earthquake experience. arch iran med. 2009;12(4):347-52. 16. rajagopalan s. crush injuries and the crush syndrome. med j armed forces india. 2010;66(4):317-20. 17. kasper d, fauci a, hauser s, longo d, jameson j, loscalzo j. harrison’s principles of internal medicine 19/e (vol. 1 & vol. 2): mcgraw hill professional; 2015. 18. safari s, yousefifard m, hashemi b, baratloo a, forouzanfar mm, rahmati f, et al. the value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and metaanalysis. clin exp nephrol. 2016:1-9. 19. safari s, yousefifard m, baikpour m, rahimi-movaghar v, abiri s, falaki m, et al. validation of thoracic injury rule out criteria as a decision instrument for screening of chest radiography in blunt thoracic trauma. j clin orthop trauma. 2016;[in press]. 20. shojaee m, faridaalaee g, yousefifard m, yaseri m, arhami dolatabadi a, sabzghabaei a, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chin j traumatol. 2014;17(1):19-24. 21. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, haji ghanbari mj, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. emerg (tehran). 2015;3(4):127-36. 22. yousefifard m, baikpour m, ghelichkhani p, asady h, shahsavari nia k, moghadas jafari a, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. emerg (tehran). 2016;4(1):1-10. 23. allister c. cardiac arrest after crush injury. bmj. 1983;287(6391):531-2. 24. better os. the crush syndrome revisited (1940-1990). nephron. 1990;55(2):97-103. 25. sever ms, erek e, vanholder r, kantarci g, yavuz m, turkmen a, et al. serum potassium in the crush syndrome victims of the marmara disaster. clin nephrol. 2003;59(5):326-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitation: conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e20 https://doi.org/10.22037/aaem.v9i1.1070 or i g i n a l re s e a rc h effects of intravenous lipid emulsion on tramadolinduced seizure; a randomized clinical trial amir mohammad kazemifar1, zohreh yazdi1, abbas bedram1, javad mahmoudi2, mojtaba ziaee3∗ 1. faculty of medicine, qazvin university of medical sciences, qazvin, iran. 2. neuroscience research center, tabriz university of medical sciences, tabriz, iran. 3. medicinal plants research center, maragheh university of medical sciences, maragheh, iran. received: january 2021; accepted: january 2021; published online: 20 february 2021 abstract: introduction: there are numerous studies on the efficacy of intralipid emulsion (ile) in various xenobiotic toxicities. this study aimed to evaluate the potential role of ile as an antidote in tramadol-induced seizure. methods: a single-blind clinical trial was undertaken to establish the efficacy and safety of ile in patients with acute tramadol intoxication, who referred to booali hospital in qazvin. patients were randomly assigned to 2 groups. the control group received standard care while the intervention group received intralipid emulsion (ile) 20% in addition to the standard care. the occurrence of in-hospital seizure was compared between the groups. results: 80 patients who abused tramadol and met the study criteria were randomly assigned to either the intervention (40 cases) or the control (40 cases) group. seizure occurred in 44 (56%) patients before admission to the emergency department. there were not any statistical differences between the groups regarding sex distribution (p=0.513) and mean age (p=0.19), presenting vital signs (p < 0.05), laboratory findings (p < 0.05), and mean abused dose of tramadol (p = 0.472) as well as occurrence of prehospital seizure (p = 0.7). in-hospital seizure occurred in 15 (18.75%) cases (all in the control group; p < 0.001). the mean duration of admission was 2.01 ± 1.13 days in the control group and 2.15 ± 1.04 days in the intervention group (p = 0.6). the number needed to treat for ile to prevent tramadol-induced seizure was 2.7 (37.5% absolute risk reduction). conclusion: the findings of this study supported ile administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures. keywords: tramadol; soybean oil, phospholipid emulsion; poisoning; seizure; clinical trial cite this article as: kazemifara m, yazdi z, bedram a, mahmoudi j, ziaee m. effects of intravenous lipid emulsion on tramadol-induced seizure; a randomized clinical trial. arch acad emerg med. 2021; 9(1): e20. 1. introduction tramadol is a synthetic analgesic drug that exerts opioid and non-opioid effects, acting predominantly on the central nervous system (cns). it is prescribed to treat moderate to severe pain such as postoperative or chronic pain (1). although it appears to be a safe and effective analgesic, there are evidence that have linked tramadol to illegal abuse and poisoning and even anaphylactoid reactions (2). the prevalence of tramadol abuse and poisoning has risen significantly in the middle east and many other countries (3). major clin∗corresponding author: mojtaba ziaee; medicinal plants research center, maragheh university of medical sciences, maragheh, iran. tel: +98 41 33 37 22 52, mobile: +98 914 313 1830, e-mail: ziaee.m@mrgums.ac.ir ; mjziaee@gmail.com, orcid: https://orcid.org/0000-0002-9725-3033 ical findings of tramadol intoxication are seizures, apnea, hemodynamic changes (bradycardia or tachycardia and hypotension), and coma (4). tramadol-induced seizures are mostly not associated with dose and occur within the first 4-6 hours (5). several studies have reported successful resuscitation of these patients through the utilization of intravenous lipid emulsion (ile) as an antidote for the treatment of hemodynamic or neurological symptoms of poisoning with lipophilic xenobiotics (6). although several mechanisms have been postulated for the resuscitative properties of ile, two theories are more interesting: lipid sink (partitioning) and enhanced metabolism theories. the partitioning theory suggests that ile administration compartmentalizes the lipophilic drugs into the lipid phase and detaches them from the target tissues. decreased drug concentrations in blood flow facilitate the elimination of the xenobiotics from the affected organs through the generation of a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a m. kazemifar et al. 2 concentration gradient (7). the enhanced metabolism theory argues that infusion of ile elevates cardiac metabolism and has inotropic effects. recent studies claimed that ile administration increased left ventricular contractility. both hypotheses were established based on pieces of evidence indicating that lipid therapy shows efficacy on a variety of xenobiotic groups with different receptor specificities. thus, lipid therapy may counteract particular poisons either through receptor-independent pathways or by a common downstream mechanism. despite the existence of numerous studies on ile efficacy and the satisfactory findings in various xenobiotics toxicities, limited clinical researches have studied ile in patients who have overdosed on tramadol and experienced seizures (8). this study aimed to evaluate the potential role of ile as an antidote in tramadol-induced seizure. 2. methods 2.1. study design and setting this randomized, single-blinded, clinical trial was conducted on 80 patients with acute tramadol poisoning who were referred to the emergency department (ed) of booali hospital, qazvin, iran, between august 2017 and september 2018. the research procedure was approved by the ethics committee of qazvin university of medical science (code: ir.qums.rec.1395.267) and was registered at the iranian registry of clinical trials under registration number irct2017050120951n3. written informed consent was received from all patients after a brief presentation, and before they participated in the study. the research was designed as a pilot and thus, had a relatively limited sample size. 2.2. study population 80 consecutive cases, who were admitted to the ed during the study period, were studied. patients were eligible for participation in the study if they met the following criteria: 1) adults (16 years and above), 2) tramadol ingestion (based on patient’s history), 3) clinical presentations of tramadol overdose and 4) referring to ed within 4 hours of tramadol intake. patients were excluded from the study if they met the following conditions: 1) multiple drug ingestion, 2) underlying heart disease, 3) hypersensitivity to the drug, 4) any previous history of seizure, and 5) abnormality in blood oxygen, electrolyte, and biochemical analysis. multiple drug intakes were characterized based on history with or without confirmed urine or serum drug screening test. 2.3. data gathering the baseline characteristics of the patients including sex, age, vital signs (pulse rate, respiratory rate, blood pressure, glasgow coma scale, and oxygen saturation), history of seizure before admission to ed, dosage of abused drug, and lab tests were evaluated on admission of patients. the patients were randomly assigned to control and intervention groups using a computer-generated randomization table and simple randomization method. all participants were blinded to the type of treatment received until the completion of the study. blood samples were drawn for assessing blood sugar, blood urea nitrogen (bun), creatinine (cr), sodium (na+), potassium (k+), liver function, hematological parameters. the diagnosis of seizures before admission to the emergency department was done based on an accurate medical history and reports taken from the witnesses who accompanied the patient and verified via scars of tongue biting. inhospital events such as seizures were accurately monitored by the well-trained medical staff. an internal medicine specialist was responsible for data gathering. 2.4. intervention the patients in the intervention group received a single dose of 12 ml/kg of intralipid emulsion (ile) 20% (30% as a bolus dose and the remaining infused over 3 hours) after stabilization along with routine treatment, while the control group only received the standard medical treatment including gut decontamination and adequate supportive care. the patients were monitored for vital parameters and seizures every 10 minutes. 2.5. outcomes the main outcome of present study was the effect of ile on occurrence and frequency of tramadol-induced seizure. 2.6. statistical analysis data were tabulated using microsoft excel and analyzed using spss software (v 21.0; spss inc., chicago, il). baseline data were presented using mean ± standard deviation or frequency (%). continuous variables were analyzed using unpaired student’s t-test. p-values less than 0.05 were considered significant. 3. results 3.1. baseline characteristics of participants 80 patients who abused tramadol and met the study criteria were randomly assigned to intervention (40 cases) or control (40 cases) groups. figure 1 demonstrates the breakdown of all patients enrolled in the study. seizure had occurred in 44 (56%) patients before admission to the emergency department. table 1 compares the baseline characteristics of patients between the groups. there were not any statistical differences between the groups regarding sex distribution (p = 0.513) and mean age (p = 0.19), presenting vital signs (p < 0.05), laboratory findings (p < 0.05), and mean abused dose this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e20 of tramadol (p = 0.472) as well as occurrence of prehospital seizure (p = 0. 7). 3.2. outcomes table 2 compares the studied outcomes between the two groups. in-hospital seizure occurred in 15 (18.75%) cases (all in control group; p < 0.001). all documented in-hospital seizures were tonic-colonic. the mean duration of admission was 2.01 ± 1.13 days in the control group and 2.15 ± 1.04 days in the intervention group (p = 0.6). the number needed to treat for ile to prevent tramadol-induced seizure was 2.7 (37.5% absolute risk reduction). it means that 2.7 patients should be treated with ile so that it can prevent one tramadol-induced seizure. 4. discussion current findings advocate ile administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures. ile has been approved for parenteral nutrition and as a vehicle for lipophilic medicines by the food and drug administration (fda) since a long time ago. however, several studies have reported the efficacy of using ile as an antidote in poisoning with different drugs with no reported adverse effects. the first clinical study conducted by rosenblatt in 2006 showed that ile infusion attenuates cns toxicity of local anesthetics, and increases consciousness score on glasgow coma scale (9). the use of opioids, including tramadol, and subsequent poisoning have overwhelmingly increased in recent years (10). the most common symptoms of tramadol intoxication are a seizure, various cardiac dysrhythmias, and in some cases death. seizure is the most important presentation of tramadol overdose, and it has been reported in 54.4% of the patients (11, 12). a recent experiment showed the efficacy of ile administration in managing tramadol poisoning (8). in the current research, ile was able to attenuate tramadol-induced seizures, and was efficacious up to 100% with 12 ml/kg doses. the occurrence of seizures after tramadol consumption has been reported in many studies. several studies noted the incidence of seizures after tramadol overdose, while some other studies claimed the dose-independent manner of this phenomenon (13). according to the results, 44 out of 80 patients (56.2%) admitted to the emergency department had experienced a seizure before entering the emergency department. in the current study, 15 patients (37%) in the control group experienced a seizure during the hospital admission period. talaei et al. described seizures in 46% of tramadol abusers (13), while jovanović-čupićnoted reported that 54.4% of patients experienced seizure with the dose range of 250–2500 mg (14). in this study, the lowest dose resulting in seizure was 50 mg, which was in contrast with results by marquardt et al. (15), spiller (16), and farzaneh et al. (17), who reported the lowest dose of tramadol leading to seizure as 200, 500, and 1000, respectively. in a case report by beyaz et al. 75 mg of tramadol caused a tonic-colonic seizure (18). taghaddosinejad and colleagues (19) reported two cases of seizure at a dose of 100 mg and the results of our study is in accordance with these findings. this study was built upon the previous study by vahabzadeh et al., which focused on the effect of intralipid infusion on seizure prevention in rabbits with acute tramadol intoxication. they demonstrated the positive effect of ile on seizure prevention, which is consistent with the findings of the present study (20). according to the results, ile can be used as an effective antidote against seizure and possibly other adverse outcomes in patients with tramadol intoxication. unfortunately, there is no high-quality controlled clinical study in this regard and we suggest performing large-scale controlled clinical trials to assess lipid emulsion therapy as a first-line therapy for indications such as tramadol poisoning. lipid emulsions may have some adverse side effects. we suggest performing larger prospective studies along with patient follow-up in the future to elucidate the possible therapeutic effects and latent complications of ile in tramadol-induced toxicities. 5. limitations there were some limitations to our research. the study was done as a pilot with relatively limited participants. in this respect, another multicenter analysis must be done with a greater sample size. considering the incomplete information about the history of using tramadol or other drugs in patients, the analysis, and comparison between the history tramadol use and seizure was not possible. 6. conclusion the findings of this study supported ile administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures. however, larger prospective studies along with patient followup should be performed in the future to elucidate the possible therapeutic effects and latent complications of ile in tramadol-induced toxicities. 7. declarations 7.1. acknowledgment the authors would like to express their gratitude to all others participating in this project through assisting data collecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a m. kazemifar et al. 4 tions, nurses, and emergency staff. 7.2. author contributions the conception and design of the work by ak, mz and zy; data acquisition by ab and ak; analysis and interpretation of data by ak, jm, mz and zy; drafting the work by mz and ab; revising it critically for important intellectual content by jm and mz; all the authors approved the final version to be published; and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work will be answered. 7.3. funding/support this study was supported by a grant received from qazvin university of medical sciences. 7.4. conflict of interest the authors declare that they have no competing interests. references 1. king s, forbes k, hanks g, ferro c, chambers e. a systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a european palliative care research collaborative opioid guidelines project. palliat med. 2011;25(5):525-52. 2. mori f, barni s, manfredi m, sarti l, pecorari l, pucci n, et al. anaphylaxis to intravenous tramadol in a child. pharmacology. 2015;96(5-6):256-8. 3. bassiony mm, salah el-deen gm, yousef u, raya y, abdel-ghani mm, el-gohari h, et al. adolescent tramadol use and abuse in egypt. am j drug alcohol abuse 2015;41(3):206-11. 4. vahabzadeh m, moshiri m, mohammadpour ah, hosseinzadeh h. promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. reg anesth pain med. 2013;38(5):425-30. 5. shadnia s, soltaninejad k, heydari k, sasanian g, abdollahi mjh, toxicology e. tramadol intoxication: a review of 114 cases. hum exp toxicol. 2008;27(3):201-5. 6. cao d, heard k, foran m, koyfman a. intravenous lipid emulsion in the emergency department: a systematic review of recent literature. j emerg med. 2015;48(3):387-97. 7. french d, smollin c, ruan w, wong a, drasner k, wu ahjct. partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. clin toxicol (phila). 2011;49(9):801-9. 8. vahabzadeh m, moshiri m, mohammadpour ah, hosseinzadeh h. promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. regional anesthesia & pain medicine. 2013;38(5):425-30. 9. rosenblatt ma, abel m, fischer gw, itzkovich cj, eisenkraft jbjatjotasoa. successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. anesthesiology. 2006;105(1):217-8. 10. ziaee m, hajizadeh r, khorrami a, sepehrvand n, momtaz s, ghaffari s. cardiovascular complications of chronic opium consumption: a narrative review article. iran j public health. 2019;48(12):2154-64. 11. talaie h, panahandeh r, fayaznouri mr, asadi z, abdollahi mjjomt. dose-independent occurrence of seizure with tramadol. toxicol invest. 2009;5(2):63-7. 12. ahmadimanesh m, shadnia s, rouini mr, sheikholeslami b, nasab sa, ghazi-khansari mjdm, et al. correlation between plasma concentrations of tramadol and its metabolites and the incidence of seizure in tramadol-intoxicated patients. drug metab pers ther. 2018;33(2):75-83. 13. talaie h, panahandeh r, fayaznouri mr, asadi z, abdollahi mjjomt. dose-independent occurrence of seizure with tramadol. 2009;5(2):63-7. 14. jovanović-čupić v, martinović ž, nešić njct. seizures associated with intoxication and abuse of tramadol. clin toxicol (phila). 2006;44(2):143-6. 15. marquardt ka, alsop ja, albertson te. tramadol exposures reported to statewide poison control system. ann pharmacother. 2005;39(6):1039-44. 16. spiller ha, gorman se, villalobos d, benson be, ruskosky dr, stancavage mm, et al. prospective multicenter evaluation of tramadol exposure. j toxicol clin toxicol. 1997;35(4):361-4. 17. farzaneh e, samadzadeh m, shahbazzadegan b, sayadrezai i, mostafazadeh b, sarbandi farahani a, et al. comparing the frequency of seizure in patients intoxicated with tramadol treated with or without naloxone. j res med sci. 2012;30(197). 18. beyaz sg, sonbahar t, bayar f, erdem afja, essays, researches. seizures associated with low-dose tramadol for chronic pain treatment. anesth essays res 2016;10(2):376. 19. taghaddosinejad f, mehrpour o, afshari r, seghatoleslami a, abdollahi m, dart rc. factors related to seizure in tramadol poisoning and its blood concentration. j med toxicol. 2011;7(3):183. 20. vahabzadeh m, moshiri m, mohammadpour ah, hosseinzadeh h. promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. regional anesthesia and pain medicine. 2013;38(5):425-30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e20 table 1: comparison of baseline characterises of patients between the groups parameters intervention (n = 40) control (n = 40) p-value sex male 34 (85) 36 (90) 0.513 female 6 (15) 4 (10) age (year) mean ± sd 25.1 ± 8.1 22.8 ± 5.7 0.190 vital sign (on admission) glasgow coma scale 13.65 ± 1.76 13.63 ± 1.87 0.951 systolic blood pressure(mmhg) 118.5 ± 8.7 121.7 ± 1 0.177 diastolic blood pressure(mmhg) 77.5 ± 9.6 77.3± 10.2 0.842 heart rate (bpm) 85.7 ± 8 84.3 ± 7.5 0.463 respiratory rate /minute) 15.2 ± 3 14.5 ± 4.2 0.547 sao2 (%) 94.0±2.5 93.0±3.4 0.587 laboratory findings tramadol dose(mg) 229.8 ± 135.5 195 ± 156.5 0.472 blood sugar (mg/dl) 112 ± 44.6 109 ± 39.5 0.682 serum sodium (meq/l) 138.3 ± 3.1 137.8 ± 3.2 0.520 serum potassium (meq/l) 4.3 ± 0.36 4.2 ± 0.39 0.119 creatinine (mq/dl ) 0.91 0.16 0.89 ± 0.15 0.791 ph 7.39 ± 0.37 7.39 ± 0.36 0.830 alt (iu/l) 24.2±10.3 27±9.5 0.648 ast(iu/l) 34.92±9.31 35.07±13.1 0.195 bun(mg/dl) 25.4 ± 7.3 26.1 ± 6.6 0.547 hemoglobin (g/dl) 13.8± 1.5 13.6± 1.8 0.842 pre-hospital seizure yes 21 (52.5) 23 (57.5) 0.700 data are presented as mean ± standard deviation (sd) or frequency (%). alt: alanine aminotransferase; ast: aspartate aminotransferase; bun: blood urea nitrogen. table 2: comparison of studied outcomes between the groups outcome intervention (n = 40) control (n = 40) p-value in-hospital seizure yes 0 (0.00) 15 (37.5) <0.001 no 40(100) 25(62.5) duration of hospitalization (days) 1 14 (35.0) 18 (45.0) 2 12 (30.0) 9 (22.5) 0.616 3 11 (27.5) 10 (25.0) 4 2(5.0) 1(2.5) 5 1(2.5) 2(5.0) data are persecuted as number (%). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a m. kazemifar et al. 6 figure 1: study enrollment and distribution of studied patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e72 or i g i n a l re s e a rc h factors associated with return of spontaneous circulation following pre-hospital cardiac arrest in daegu metropolitan city, south korea; a cross-sectional study hyun-ok jung1, seung-woo han2∗ 1. college of nursing, the research institute of nursing science, dageu catholic university, daegu, korea 2. department of emergency medical technology, kyungil university, korea. received: june 2022; accepted: july 2022; published online: 1 september 2022 abstract: introduction: the probability of return of spontaneous circulation (rosc) in cardiac arrest cases in prehospital setting is still low. this study aimed to identify the factors that may improve the rate of rosc in patients with pre-hospital cardiac arrest. methods: this retrospective cross-sectional study is a secondary data analysis of cardiac arrest patients, who were managed by paramedics in the pre-hospital setting, from january 1, 2019, to december 31, 2019, in daegu, south korea. the association of rosc with place of arrest occurrence, cardiac arrest being witnessed, performing cardiopulmonary resuscitation (cpr), using compression device and defibrillator, administration of epinephrine, and intubation was analyzed and independent predictive factors of rosc were reported. results: 2750 out-of-hospital cardiac arrest cases, which were managed by paramedics in the pre-hospital setting were studied. 2034 (86.9%) cases of arrest had occurred at home, 2028 (73.7%) were not witnessed, and cpr was not performed for 1721 (64.1%) cases. rosc before arriving to emergency department (ed) was more probable if the cardiac arrest was witnessed (p < 0.001), if cpr was performed (p = 0.044), if a mechanical compression device was used (p < 0.001), if a first-aid defibrillator was used (p < 0.001), and if intravenous access was secured (p < 0.001). multivariate regression analysis revealed that using mechanical compression device (or: 0.18; 95% ci = 0.08 0.40; p = 0.001), using first-aid defibrillator (or: 3.13; 95% ci = 1.40 6.99; p = 0.005), administration of epinephrine (or: 6.57; 95% ci = 2.16 19.53; p = 0.001), and intubation (or: 1.82; 95% ci = 1.04-3.19; p = 0.001) were independent predictive factors of rosc before arrival to ed. conclusion: it seems that chest compression by hand instead of using chest compression device, using defibrillator, epinephrine administration, and intubation my increase the probability of rosc in pre-hospital arrest cases. keywords: out-of-hospital cardiac arrest; return of spontaneous circulation; patients; korea cite this article as: jung h-o, han s-w. factors associated with return of spontaneous circulation following pre-hospital cardiac arrest in daegu metropolitan city, south korea; a cross-sectional study. arch acad emerg med. 2022; 10(1): e72. https://doi.org/10.22037/aaem.v10i1.1589. 1. introduction the rate of death due to cardiovascular system disease in south korea was 117.4 per 100,000 people in 2019 (1). sudden cardiac arrest (sca) results in death due to hemodynamic failure if the heart is not restarted in minutes (2). in the united states, more than 550,000 patients suffer sca, before and during hospitalization, each year. sca accounts for more than half of cardiovascular mortalities and is a major ∗corresponding author: seung-woo han; gamasilgil hayangeup, gyeongbuk 38428 korea. email: swhan@kiu.ac.kr, tel: 82-53-600-5691, fax: 82-53600-5699, orcid: http://orcid.org/0000-0001-9144-3285. national concern (3). the probability of patients recovering from cardiac arrest that occurred before hospital arrival in korea increased from 1.1% in 2007 to 7.6% in 2017, but this recovery rate is still very low compared to developed countries, such as the u.s. 11.4%, sweden 14.0%, and norway 13.0% (4, 5). to solve the practical problems associated with emergency medical treatment, the korean government has been actively studying the prevention and management of diseases by establishing cardiovascular and cerebrovascular prevention centers in korea (6). daegu metropolitan city (dmc) in southeastern korea has the fourth largest population (2.4 million) in the country. the rate of emergency department (ed) deaths among ed users this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h-o. jung et al. 2 in dmc was 0.418%, which was the highest in the country (7). identifying the factors that influence the return of spontaneous circulation (rosc) in patients with out-of-hospital cardiac arrest (ohca), where a rapid response is required, may improve community participation and emergency care. previous studies have shown that pre-hospital factors that are closely related to the patient survival rate include: whether the patient was witnessed, if witnesses performed cardiopulmonary resuscitation (cpr), and whether the rosc occurred spontaneously (8, 9). however, the factors that affect rosc have not been studied in depth by country or region. because the environment and emergency medical care resources in each country are different, rapid treatment and methods of coping with patients who have pre-hospital cardiac arrest may also differ. this study aimed to identify the factors that may improve rate of rosc in patients with prehospital cardiac arrest. 2. methods 2.1. study design and setting this retrospective cross-sectional study is a secondary data analysis of cardiac arrest patients, who were managed in the pre-hospital setting by paramedics, from january 1, 2019, to december 31, 2019, in daegu, south korea. the association of arrest characteristics with rosc were analyzed and independent predictive factors of rosc were reported. the data in this study were approved and obtained from the emergency activity log and cardiopulmonary arrest detailed situation chart prepared by paramedics at the dmc fire department. we obtained approval from the k university institutional review board (irb) for the exemption of deliberation (irb1041459-202103-hr-003-01). we anonymized the emergency activity log and the details of the cardiopulmonary arrest detailed situation table. 2.2. participants cases for which cpr was withheld or suspended by paramedics due to apparent death or other causes were not considered. specifically, the subjects included in this study were cases of cardiac arrest provided by the daegu metropolitan city fire department. 2.3. data gathering for data collection, the purpose and suitability of the study were explained to the head of the dmc fire department, and data use was approved. this study selected and investigated items that may affect rosc, as suggested by the emergency activity log and the detailed cardiopulmonary arrest schedule prepared by paramedics. in addition, vaguely written items, for example, subjects with blanks on whether or not to recover spontaneous circulation or subjects whose occurtable 1: baseline characteristics of studied out-of-hospital cardiac arrest cases characteristics number (%) underlying disease yes 1879 (90.3) no 202 (9.7) occurrence place house (parking lot, yard) 2034 (86.9) ambulance 99 (4.2) nursing institution (medical facility) 101 (4.3) other 106 (4.6) witnessed yes 722 (26.3) no 2028 (73.7) cpr performed yes 963 (35.9) no 1721(64.1) using mechanical chest compression device yes 856 (39.6) no 1307 (60.4) using first-aid defibrillator yes 223 (8.1) no 2527 (91.9) epinephrine administered yes 380 (31.7) no 819 (68.3) intubation performed yes 504 (42.0) no 695 (58.0) recovery of spontaneous circulation yes 187 (14.3) no 1120 (85.7) * the sum of the case numbers may not match the total number due to the missing data. cpr: cardiopulmonary resuscitation. rence location is not clear, were reassessed until the two researchers agreed. the dependent variables were the rosc and independent variables were the type and place of occurrence, whether there were witnesses to the cardiac arrest, if cpr was performed, if a mechanical compression device or first-aid defibrillator was used, whether epinephrine had been administered intravenously, and if intubation was performed. the raw data were provided by the dmc fire department, and to ensure the anonymity of patients, data such as name, gender, age, and occupation of the patients were deleted. in this study, two experts in the relevant field gathered and selected variables suitable for this study. and the selected variables were used after final review by one emergency medical expert. 2.4. statistical analysis in this study, the ibm spss/win 23.0 program was used for data analysis. to confirm the difference in rosc based on this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e72 table 2: association between different pre-hospital arrest characteristics and return of spontaneous circulation (rosc) before arriving to emergency department characteristics rosc* p yes (n = 187) no (n = 1120) underlying disease yes 159 (15.7) 852 (84.3) 0.850 no 9 (16.4) 46 (83.6) place of occurrence house (parking lot, yard) 101 (12.0) 742 (88.0) in an ambulance 13 (13.8) 81 (86.2) 0.872 nursing institution (medical facility) 6 (9.5) 57 (90.5) other 7 (13.0) 47 (87.0) witnessed yes 122 (19.9) 490 (80.1) 0.001 no 65 (9.4) 630 (90.6) cpr performed yes 117 (16.0) 616 (84.0) 0.044 no 58 (11.1) 464 (88.9) using mechanical chest compression device yes 61 (7.1) 795 (92.9) 0.001 no 107 (27.6) 281 (72.4) using first-aid defibrillator yes 89 (40.3) 132 (59.7) 0.001 no 98 (9.0) 988 (91.0) epinephrine administered yes 87 (23.0) 291 (77.0) 0.001 no 13 (6.4) 189 (93.6) intubation performed yes 80 (15.9) 422 (84.1) 0.052 no 20 (25.6) 58 (74.4) * the sum of the case numbers may not match the total number due to the missing data. data are presented as number (%). cpr: cardiopulmonary resuscitation. the subjects’ general characteristics, we calculated the frequency and percentage and performed a cross-analysis using a χ2-test. we conducted a complex sample logistic regression analysis to identify the factors that affected rosc. in this study, statistics were applied to the raw data without manipulation or alteration. 3. results 3.1. baseline characteristics of participants 2750 out-of-hospital cardiac arrest cases, which were managed by paramedics in pre-hospital setting were studied. table 1 summarizes the baseline characteristics of studied arrest cases. 2034 (86.9%) cases of arrest had occurred at home, 2028 (73.7%) were not witnessed, and cpr was not performed for 1721 (64.1%) cases. 3.2. associated factors of rosc before arriving to ed the recovery of spontaneous circulation was experienced by 187 (14.3%) cases. table 2 evaluates the association of rosc with different pre-hospital arrest characteristics. based on univariate analysis, rosc before arriving to ed was more probable if the cardiac arrest was witnessed (χ2 = 29.727, p < 0.001), if cpr was performed (χ2 = 6.232, p = 0.044), if a mechanical compression device was used (χ2 = 95.596, p < 0.001), if a first-aid defibrillator was used (χ2 = 146.241, p < 0.001), and if intravenous access was secured (χ2 = 25.364, p < 0.001). multivariate regression analysis introduced using mechanical compression device (or: 0.18; 95% ci = 0.08 0.40; p = 0.001), using first-aid defibrillator (or: 3.13; 95% ci = 1.40 6.99; p = 0.005), administration of epinephrine (or: 6.57; 95% ci = 2.16 19.53; p = 0.001), and intubation (or: 1.82; 95% ci = 1.04-3.19; p = 0.001) as independent predictive factors of rosc before arrival to ed (table 3). 4. discussion it seems that chest compression by hand instead of using chest compression device, using defibrillator, epinephrine administration, and intubation may increase the probability of rosc in pre-hospital arrest cases. this study showed that mechanical compression devices this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h-o. jung et al. 4 table 3: association between different pre-hospital arrest characteristics and return of spontaneous circulation (rosc) before arriving to emergency department characteristics b or 95% ci p using mechanical chest compression device yes -1.70 0.18 0.08-0.40 0.001 no 1.00 1.00 using first-aid defibrillator yes 1.14 3.13 1.40-6.99 0.005 no 1.00 1.00 epinephrine administration yes 1.88 6.57 2.16-19.53 0.001 no 1.00 1.00 intubation performed yes 0.60 1.82 1.04-3.19 0.001 no 1.00 1.00 or: odds ration; ci: confidence interval. are less effective than manual cpr in achieving rosc. this result contradicts prior studies (10, 11) that showed that mechanical compression devices were more effective than cpr in achieving rosc and a review of 1,187 systems that showed no significant difference between mechanical compression devices and hand cpr in achieving rosc (12). this conflict may be a result of the situational environment, as paramedics in korea tend to prefer hand cpr over mechanical compression unless the ambulance ride is long. in addition, mechanical compression devices are not always available in ambulances across korea. this study determined that a first aid defibrillator increased the probability of rosc by 3.13 times. a previous study (13) suggested that improvements in cpr quality and automated external defibrillator (aed) availability can improve the likelihood that a patient will survive heart failure. the latest advanced life support (als) guidelines suggest that about 20% of patients with out-of-hospital cardiac arrests experience ventricular tachycardia or ventricular fibrillation (14). in prehospital patients, especially during ventricular tachycardia or ventricular fibrillation, a reduction in the time before aed is applied increases the probability of obtaining rosc (15). this finding is consistent with the results of a study conducted only on cardiac arrest patients who had been treated using an aed, which showed that defibrillation was possible 63.6 ∼ 70.8% of the time, resulting in a high rate of rosc (16, 17). therefore, early application of an aed to restore appropriate rhythms can achieve rosc and contributes to the survival of pre-hospital cardiac arrest patients. this study also showed that intravenous administration of epinephrine increased the likelihood of rosc before arrival at the emergency room. previous studies found (18) that epinephrine injection during an out-of-hospital cardiac arrest increases the probability of both rosc and short-term survival. in general, epinephrine should be injected as soon as possible when arrhythmia does not respond to aed (19). in another study (20), the average time before intravenous injection during cardiac arrest outside the hospital was 19.4 minutes. people who receive injected epinephrine within 10 minutes are approximately 4.52 times more likely to show rosc than those who receive it within 30 minutes. although this study only investigated the administration of epinephrine, based on previous studies, it is believed that the rapid injection of epinephrine, will have a positive effect on rosc. these findings suggest that when pre-hospital cardiac arrest occurs, rapid treatment by paramedics and fast and skilled application of intravenous epinephrine is needed. however, paramedics have different proficiencies, so the success of intravenous epinephrine application can vary. korea is training paramedics on securing intravenous access, but the difference in paramedic skill levels must be corrected. finally, in this study, intubation increased the probability of rosc before arrival in the emergency room. in cardiopulmonary resuscitation, cardiac output and coronary perfusion pressure are related to rosc in cardiac arrest patients, and provision of sufficient respiratory volume through appropriate intubation during cpr is an important factor in rosc (21). therefore, it is considered that intubation can contribute to improving the survival rate of out-of-hospital cardiac arrest patients. the various independent variables that were identified should be verified. the effects of time on spontaneous circulation should be evaluated. for example, the relationship between the time of emergency room arrival or the time to achieve intravenous access and the probability of rosc must be examined. in addition, the samples provided in this study are raw data, in which personal characteristics, such as gender, age, and occupation, which may affect rosc, have been deleted to ensure anonymity. so, if these factors are presented more this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e72 clearly, it can help to identify their probable effect on rosc. we suggest that continuous cpr education should be provided for residents. cpr education is being provided on a regional basis in korea, but has not been implemented across the country. therefore, national support may improve the cpr capabilities of local people. increasing the number of emergency rooms is also necessary, as this tends to be proportional to the population, making them unavailable to residents who live outside of cities. 5. limitations this study used raw data of acute cardiac arrest patients in daegu metropolitan city during 1 year in 2019. however, it should be noted that there is a limit to confirming the factors influencing rosc in patients with acute cardiac arrest with one year of data from one region. because, a capital city with a population close to 10 million like seoul or the current covid-19 situation could affect rosc. therefore, a study using multi-year data will be helpful in more accurately identifying the influencing factors. 6. conclusion it seems that chest compression by hand instead of using chest compression device, using defibrillator, epinephrine administration, and intubation may increase the probability of rosc in pre-hospital arrest cases. 7. declarations 7.1. acknowledgments we would like to thank the daegu metropolitan city fire department and its staff for their cooperation in the research. it is expected that this study will contribute to the improvement of rosc. 7.2. authors’ contributions conceptualization: hyun-ok jung, seung-woo han data curation: hyun-ok jung, seung-woo han methodology: seung-woo han project administration & supervision & validation: seungwoo han writing-original draft, review & editing: hyun-ok jung, seung-woo han 7.3. funding and supports no funding was received for this study. 7.4. conflict of interest no potential conflict of interest was reported by the authors. references 1. korea s. annual report on domestic statistics by topic 2021 [available from: https://kosis.kr/statisticslist/statis ticslistindex.do?men uid=m_01_01&vwcd=mt_ztitle &parmtabid=m_01_01 &outlink=y&entrtype=. 2. pérez ab. exercise as the cornerstone of cardiovascular prevention. rev esp cardiol (eng ed). 2008;61(5):514-28. 3. go as, mozaffarian d, roger vl, benjamin ej, berry jd, blaha mj, et al. heart disease and stroke statistics—2014 update: a report from the american heart association. circulation. 2014;129(3):e28-e292. 4. prevention cfdca. 2006-2017 survey statistics for acute cardiac arrest, issued by: disease prevention center for chronic diseases. phwr. 2018;11(52):1-34. 5. members wg, roger vl, go as, lloyd-jones dm, benjamin ej, berry jd, et al. heart disease and stroke statistics—2012 update: a report from the american heart association. circulation. 2012;125(1):e2-e220. 6. korea s. annual report on the population statistics 2021[available from: https://kosis.kr/stathtml/stathtml .do?orgid=202&tblid =dt_202n_b4&conn_path=i2. 7. center knli. law on emergency medical services 2019 [available from: http://www.law.go.kr/lsw/eng/englsa stsc.do?menuid =1&datacls=lsastsc&cptoficd=1352000 #cptofi1352000. 8. jacobs i, nadkarni v, arrest itfoc, outcomes cr, participants c, bahr j, et al. cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the international liaison committee on resuscitation (american heart association, european resuscitation council, australian resuscitation council, new zealand resuscitation council, heart and stroke foundation of canada, interamerican heart foundation, resuscitation councils of southern africa). circulation. 2004;110(21):3385-97. 9. perkins gd, jacobs ig, nadkarni vm, berg ra, bhanji f, biarent d, et al. cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the utstein resuscitation registry templates for out-of-hospital cardiac arrest: a statement for healthcare professionals from a task force of the international liaison committee on resuscitation (american heart association, european resuscitation council, australian and new zealand council on resuscitation, heart and stroke foundation of canada, interamerican heart foundation, resuscitation council of southern africa, resuscitation council of asia); and the american heart association emergency cardiovascular care committee and the council on cardiopulmonary, critical care, perioperative and resuscitation. circulation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h-o. jung et al. 6 2015;132(13):1286-300. 10. wang pl, brooks sc. mechanical versus manual chest compressions for cardiac arrest. cochrane database syst rev. 2018;8(8):cd007260. 11. lee hj. the effect of a mechanical chest compressions for out-of-hospital advanced cardiac life support. j converg inf technol. 2019;9(11):227-33. 12. brooks sc, hassan n, bigham bl, morrison lj. mechanical versus manual chest compressions for cardiac arrest. cochrane database syst rev. 2014;27(2):cd007260. 13. viereck s, møller tp, ersbøll ak, folke f, lippert f. effect of bystander cpr initiation prior to the emergency call on rosc and 30 day survival—an evaluation of 548 emergency calls. resuscitation. 2017;111:55-61. 14. soar j, deakin c, lockey a, nolan j, perkins g. 2015 resuscitation guidelines,1-36 2015 [available from: https://www.resus.org.uk/library/2015-resuscitationguidelines/guidelines-adult-advanced-life-support. 15. banerjee p, ganti l, stead tg, vera ae, vittone r, pepe pe. every one-minute delay in ems on-scene resuscitation after out-of-hospital pediatric cardiac arrest lowers rosc by 5%. resusc plus. 2021;5:100062. 16. lee js, lee hp, shon yd, ahn hc, ko by, wang sj. the study of an automated external defibrillator (aed) use by 119 rescuers in gyeonggi-do. j korean soc emerg med. 2008;19(1):15-21. 17. lee hh, seo ks, chung jm, park jb, ryoo hw, kim jk, et al. study of out-of-hospital cardiac arrest patients for whom 119 rescuers used an automated external defibrillator in the metropolitan area. j korean soc emerg med. 2008;19(3):245-52. 18. chiang wc, chen sy, ko pci, hsieh mj, wang hc, huang epc, et al. prehospital intravenous epinephrine may boost survival of patients with traumatic cardiac arrest: a retrospective cohort study. scand j trauma, resusc emerg med. 2015;23(1):1-7. 19. hansen m, schmicker rh, newgard cd, grunau b, scheuermeyer f, cheskes s, et al. time to epinephrine administration and survival from nonshockable out-ofhospital cardiac arrest among children and adults. circulation. 2018;137(19):2032-40. 20. mauch j, ringer sk, spielmann n, weiss m. intravenous versus intramuscular epinephrine administration during cardiopulmonary resuscitation–a pilot study in piglets. pediatr anesth. 2013;23(10):906-12. 21. kleinman me, brennan ee, goldberger zd, swor ra, terry m, bobrow bj, et al. part 5: adult basic life support and cardiopulmonary resuscitation quality: 2015 american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2015;132(18_suppl_2):s414-s35. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e32 https://doi.org/10.22037/aaem.v9i1.1153 rev i ew art i c l e corticosteroid therapy in management of myocarditis associated with covid-19; a systematic review of current evidence william kamarullah1∗, nurcahyani1, claudia mary josephine1, rachmatu bill multazam1, aqila ghaezany nawing1 1. indonesian cardiovascular research center, national cardiovascular center harapan kita, jakarta, indonesia. received: february 2021; accepted: march 2021; published online: 16 april 2021 abstract: introduction: myocarditis in patients infected with severe acute respiratory syndrome coronavirus 2 (sarscov-2) seems to be associated with a higher mortality rate. this study aims to summarize the latest evidence on whether the use of corticosteroids in patients with myocarditis associated with covid-19 is necessary. methods: we performed an extensive search using a combination of search terms in pubmed, europe pmc, proquest, ebscohost, and google scholar up to january 2021. full-text articles that met the predefined inclusion criteria were included in the present study. results: the full-texts of 18 articles have been reviewed. thirteen out of the eighteen (72%) patients who got corticosteroid administration experienced major clinical improvements during follow-up while the other five (28%) were experiencing uneventful events. the mean age of the reported patients was 47.8±13.2 years. there was no gender predominance. most of the reported cases were from usa (39%) followed by spain, china, and uk (11% each), while brazil, colombia, france, belgium, and italy contributed one case each. various corticosteroids were used but the most commonly applied were methylprednisolone (89%), hydrocortisone (5.5%), and prednisolone (5.5%). the most common route of administration among the studies was intravenous administration and the duration of treatment varied between one and fourteen days. conclusion: a review of the currently available literature shows that with the use of corticosteroid agents in treating myocarditis associated with covid-19, favorable outcomes are attainable. well-established randomized clinical trials are needed to evaluate the efficacy and safety of using corticosteroids in this condition. keywords: covid-19; myocarditis; corticosteroid; treatment cite this article as: kamarullah w, nurcahyani, mary josephine c, bill multazam a, ghaezany nawing a. corticosteroid therapy in management of myocarditis associated with covid-19; a systematic review of current evidence. arch acad emerg med. 2021; 9(1): e32. 1. introduction late in 2019, the world was staggered by the emergence of a new virus derived from wuhan, china, which caused severe pneumonia and was later called the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). the diease caused by the virus was named coronavirus disease 19 (covid-19) (1). this disease has led to more than 20 million active cases in 218 countries with more than 1.5 million people losing their lives (2). in the midst of this pandemic, a lot is still yet to be discovered, including the true magnitude of the disease. ∗corresponding author: william kamarullah; jl s parman kav 87, slipi, jakarta barat, postal code: 11420, jakarta, indonesia. mobile: +62811189696, fax: +6221 5684220, email: williamkamarullah@hotmail.com, orcid: http://orcid.org/0000-0001-6623-3868. it was later discovered that since it binds with angiotensin converting enzyme (ace) 2 receptors, which are also present in endothelial cells, it also affects the cardiovascular system and could manifest as myocarditis (3, 4). as many studies investigating the mechanism of multiple organ dysfunction syndrome (mods) associated with covid-19 indicated, systemic hyper inflammation syndrome has become a leading theory to explain the condition (5). currently, there is no guideline that specifically addresses use of corticosteroids in treatment of myocarditis caused by covid-19. considering that uncertainty remains regarding this issue, we aimed to systematically review the use of corticosteroids in patients with myocarditis associated with covid-19. we hypothesized that the addition of immunosuppressant therapy e.g. corticosteroids at this stage may reduce the severity of this hyperinflammatory condition. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. kamarullah et al. 2 2. methods 2.1. protocol and registration this systematic review was conducted in line with the cochrane handbook for systematic reviews of interventions and reported based on the preferred reporting items for systematic reviews and meta-analysis (prisma) (6, 7). the protocol was registered at the international prospective register of systematic reviews (prospero), under registration number crd42020223524. 2.2. search strategy due to the lack of research articles, we performed a comprehensive search on case reports/series that presents patients with myocarditis associated with covid-19 who were treated with corticosteroids using keywords ((covid 19) or (covid-19) or (coronavirus) or (coronavirus disease) or (novel coronavirus) or (novel human coronavirus) or (sars coronavirus) or (sars-cov2) or (sars-cov-2) or (sars cov-2) or (2019-ncov )) and ((myocarditis) or (carditis) or (pericarditis) or (myopericarditis)) and (corticosteroid)) from the time in which sars-cov-2 was identified ( january 2020) up until january 2021 through pubmed, europepmc, proquest, ebscohost, and google scholar. to ensure the identification of all relevant articles and publications, hand-searched articles from reference lists were also reviewed as an additional source of studies. we did not include words related to the outcomes of interest in order to obtain the largest number of search results possible. our search was in line with prisma guidelines and the flowchart in figure 1 portrays the search and screening processes. 2.3. eligibility criteria in the present study, all cases using corticosteroids for patients with myocarditis associated with covid-19 were included to be reviewed. exclusion criteria comprised animal studies, expert opinions, literature review studies, news articles, letters, editorials, guidelines, and any studies that did not mention the outcomes and specify the corticosteroid used in the study. we also limited our search to articles written in english. the outcomes of interest were all-cause mortality, clinical improvement, and hospital discharge. 2.4. study selection and data collection process articles were sorted based on whether titles or abstracts met the inclusion criteria. full-text articles were then read, any duplicate studies were deleted, and those that did not satisfy the inclusion criteria were excluded. data from the article were extracted and summarized using predesigned tables that consisted of name of the first author, year of publication, country in which the study was conducted, age and sex distribution of the patients, complete assessment of the patient, corticosteroid used, dose, route, and duration of administration, other medications, and outcomes. all steps of study selection and data collection process were conducted by all authors. disagreements regarding study selection and data extraction were resolved through consensus-based discussion. 2.5. risk of bias assessment two independent reviewers critically assessed the included studies using the joanna briggs institute’s critical assessment tool for case reports (8). the presence of bias was determined for each article using the checklist of eight questions included in table 2. the articles received a score to indicate their degree of bias (low (included) and high (excluded)). for the purpose of this study, if "yes" was answered for more than half of the eight questions on the checklist, the study was considered to have a low risk of bias. otherwise, answering "no" or “unclear” to half or more of the eight questions means the study was ascertained to have a high risk of bias and was excluded from this systematic review. discrepancies in quality ratings were resolved through consensusbased discussion. 3. results 3.1. study selection and characteristics five databases were used to find articles related to the use of corticosteroid in myocarditis associated with covid-19. we found 3479 articles; out of which, eighteen case reports were then deemed eligible for inclusion in the present study (926). a prisma flow diagram detailing the process of identification, screening, inclusion, and exclusion of studies is shown in figure 1. the mean age of the reported patients was 47.8±13.2 years (range 18–69 years). there was no gender predominance. most of the reported cases were from usa (39%) followed by spain, china, and uk (11% each), while brazil, colombia, france, belgium, and italy contributed one case each. various corticosteroids were used but the most commonly applied were methylprednisolone (89%), hydrocortisone (5.5%), and prednisolone (5.5%). the most common route of administration among the studies was intravenous administration and the duration of treatment varied between one and fourteen days. other drugs were also used as combination therapy along with corticosteroids. table 1 recounts the characteristics of the included studies. 3.2. risk of bias within studies all articles were determined to have low risk of bias. seven other studies were identified as having high risk of bias and were excluded from the final inclusion process. overall, studies did not report the adverse events resulting from the interventions. moreover, low-level evidence from the included this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e32 studies could not explain the causal relationship between the interventions and the outcomes. a complete risk of bias assessment of the comprised studies is displayed in table 2. 4. discussion eighteen case reports administering corticosteroids to subjects with myocarditis associated with covid-19 were included in this systematic review. these case reports described several types of corticosteroids, doses, routes of administration, and various outcomes. for instance, in the colombian study conducted by bernal-torres et al. (9), the authors described a 38-year-old woman without any comorbid conditions presenting with palpitations as well as general malaise since 3 days prior to admission. the patient had positive pcr examination on nasal swab for covid-19. furthermore, the patient was diagnosed with fulminant myocarditis associated with covid-19 and was treated with intravenous immunosuppressant in the form of methylprednisolone. as a result, the patient experienced clinical improvement and was discharged on day 16. case reports with similar population, without comorbid conditions, and with similar steroid therapy regimen were also provided by garau et al. (12), hu et al. (13), and naneishvili et al. (19). they showed progressive clinical improvements in various aspects. higher dose of methylprednisolone was also found to provide good clinical improvements in studies performed by salamanca et al. (22) and sampaio et al. (23). some patients with certain comorbidities such as hypertension (11, 18), heart failure (15), and type 1 diabetes mellitus (21) showed clinical improvements as well. in addition, there were also various studies that did not specify the steroid dose used (14, 16). besides, it was not uncommon to use other types of corticosteroids such as hydrocortisone (11) as well as oral prednisolone (24), which provided good clinical improvements as well. each and every study used other therapeutic agents, such as antibiotics (67%), hydroxychloroquine (50%), immunoglobulin (38%), antiviral drugs (27%), immunomodulators (27%), colchicine (22%), and other agents in addition to corticosteroid therapy to manage myocarditis associated with covid-19 in patients. regarding the outcomes, at the time of submission of those case reports, the majority of patients had survived (72%). most of the patients who reportedly passed away were noted to have both acute respiratory distress syndrome (ards) and multiple-organ failure (table 1). most of the cases in this study were reported in sufficient detail; however, four reports did not specify the dose of the corticosteroid used and three of them did not report the duration of the corticosteroid’s usage. the use of corticosteroids in myocarditis associated with covid-19 seemed to have a better outcome in this small study. from the majority of those who got myocarditis from covid-19 infection, good outcomes were reported more in those undergoing corticosteroid therapy (thirteen out of eighteen patients) compared with those who did not take a corticosteroid (five out of eighteen patients). the plausible explanation for these is that according to current researches, higher concentration of proinflammatory cytokines and chemokines were detected in patients with multiple organ dysfunction syndrome associated with covid-19 due to exaggerated immune response to the virus (27). based on this mechanism, corticosteroids can be clinically utilized to prevent the immune system from attracting more inflammatory cells to the tissue e.g. cardiac, which reduces inflammation (28). recently, the european society of cardiology has issued a guidance in dealing with cardiovascular manifestations of covid-19, yet there is no clear recommendation for the treatment of myocarditis associated with sars-cov-2 (29). myocarditis is a potentially life-threatening disease. for this reason, from the current evidence that was drawn from this systematic review, the authors of this study proposed that corticosteroid must be considered as a last resort in terms of treating patients with myocarditis associated with covid-19. this systematic review pooled case reports of patients with myocarditis caused by covid-19 infection. since this is a pooled case report, the evidence is weaker than controlled clinical trials. the number of cases was also small; there were only 18 cases from 18 studies. the findings of the pooled case reports might not apply to all patients, and the level of evidence is low. secondly, the observed outcomes cannot be solely attributed to the corticosteroid therapy due to the combination of multiple drugs. this systematic review is a hypothesis-generating study. further investigation needs to be done to obtain consecutive samples in a controlled study where the patients are blinded to corticosteroid therapy group and control group. however, the rarity of this event may impede such effort. in that case, the need for reviewing this matter in a systematic way was considered by the authors although good level of evidence were limitedly available. 5. conclusion the current systematic review showed that the use of corticosteroid agents is beneficial in improving the outcome of myocarditis associated with covid-19. the present study showed that no randomized clinical trial has been performed with the aim of assessing the efficacy and safety of using corticosteroids for treating myocarditis associated with covid19, thus well-established randomized clinical trials should be pursued in order to confirm the findings of the present review. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. kamarullah et al. 4 6. declarations 6.1. authors’ contributions wk helped in the conception and design of the study. wk, n, cmj, rbm, agn, and sd were actively involved in literature search, study selection, data extraction, extensive review, and writing the manuscript. all authors read and approved the final submitted version. 6.2. acknowledgements none. 6.3. funding the authors declared that no specific grant was received for this research from any funding agency in the public, commercial or not-for-profit sectors. there was no external funding to support this study and this study has no relationship with any industrial company. 6.4. conflict of interests the authors report no financial relationships or conflicts of interest regarding the content herein. references 1. who. coronavirus disease (covid19) pandemic 2020 [available from: https://www.who.int/emergencies/diseases/novelcoronavirus-2019. 2. who. situation reports 2020 [available from: https://www.who.int/indonesia/news/novelcoronavirus/situation-reports. 3. mokhtari t, hassani f, ghaffari n, ebrahimi b, yarahmadi a, hassanzadeh g. covid-19 and multiorgan failure: a narrative review on potential mechanisms. journal of molecular histology. 2020;51(6):613-28. 4. mai f, del pinto r, ferri c. covid-19 and cardiovascular diseases. j cardiol. 2020;76(5):453-8. 5. siddiqi hk, mehra mr. covid-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. j heart lung transplant. 2020;39(5):405-7. 6. moher d, liberati a, tetzlaff j, altman dg, the pg. preferred reporting items for systematic reviews and meta-analyses: the prisma statement. plos med. 2009;6(7):e1000097. 7. higgins j, thomas j, chandler j, cumpston m, li t, page m, et al. cochrane handbook for systematic reviews of interventions 2nd edition. chichester (uk): john wiley & sons; 2019. 8. the joanna briggs institute critical appraisal tools for use in jbi systematic reviews checklist for case reports [available from: https://joannabriggs.org/sites/default/files/201905/jbi_critical_appraisal-checklist_for_case_reports 2017_0.pdf. 9. bernal-torres w, herrera-escandón á, hurtado-rivera m, plata-mosquera ca. covid-19 fulminant myocarditis: a case report. eur heart j case rep. 2020;4(fi1):1-6. 10. coyle j, igbinomwanhia e, sanchez-nadales a, danciu s, chu c, shah n. a recovered case of covid19 myocarditis and ards treated with corticosteroids, tocilizumab, and experimental at-001. jacc case rep. 2020;2(9):1331-6. 11. doyen d, moceri p, ducreux d, dellamonica j. myocarditis in a patient with covid-19: a cause of raised troponin and ecg changes. lancet. 2020;395(10235):1516-. 12. garau g, joachim s, duliere g-l, melissopoulou m, boccar s, fraipont v, et al. sudden cardiogenic shock mimicking fulminant myocarditis in a surviving teenager affected by severe acute respiratory syndrome coronavirus 2 infection. esc heart failure. 2021;8(1):766-73. 13. hu h, ma f, wei x, fang y. coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. eur heart j. 2021;42(2):206. 14. hussain h, fadel a, alwaeli h, guardiola v. coronavirus (covid-19) fulminant myopericarditis and acute respiratory distress syndrome (ards) in a middle-aged male patient. cureus. 2020;12(6):e8808-e. 15. inciardi rm, lupi l, zaccone g, italia l, raffo m, tomasoni d, et al. cardiac involvement in a patient with coronavirus disease 2019 (covid-19). jama cardiol. 2020;5(7):819-24. 16. khalid n, chen y, case bc, shlofmitz e, wermers jp, rogers t, et al. covid-19 (sars-cov-2) and the heart an ominous association. cardiovasc revasc med. 2020;21(8):946-9. 17. khatri a, wallach f. coronavirus disease 2019 (covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: a case report and literature review. heart lung. 2020;49(6):858-63. 18. li a, garcia-bengochea y, stechel r, azari bm. management of covid-19 myopericarditis with reversal of cardiac dysfunction after blunting of cytokine storm: a case report. eur heart j case rep. 2020;4(fi1):1-6. 19. naneishvili t, khalil a, leary r, prasad n. fulminant myocarditis as an early presentation of sars-cov-2. bmj case reports. 2020;13(9):e237553. 20. irabien-ortiz á, carreras-mora j, sionis a, pàmies j, montiel j, tauron m. fulminant myocarditis due to covid19. rev esp cardiol (engl ed). 2020;73(6):503-4. 21. richard i, robinson b, dawson a, aya a, ali r. an atypical presentation of fulminant myocarditis secondary to covid-19 infection. cureus. 2020;12(7):e9179-e. 22. salamanca j, díez-villanueva p, martínez p, cecconi a, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e32 gonzález de marcos b, reyes g, et al. covid-19 "fulminant myocarditis" successfully treated with temporary mechanical circulatory support. jacc cardiovasc imaging. 2020;13(11):2457-9. 23. sampaio ppn, ferreira rm, albuquerque fn, colafranceschi as, almeida acp, nunes mav, et al. rescue venoarterial extracorporeal membrane oxygenation after cardiac arrest in covid-19 myopericarditis: a case report. cardiovasc revasc med. 2020. 24. shabbir a, camm cf, elkington a, tilling l, stirrup j, chan a, et al. myopericarditis and myositis in a patient with covid-19: a case report. european heart journal case reports. 2020;4(6):1-6. 25. tavares m, otuonye g, ayyagari l, lofters j, lui j. fulminant myocarditis in a patient with severe acute respiratory syndrome coronavirus 2. chest. 2020;158(4):a443-a4. 26. zeng jh, liu yx, yuan j, wang fx, wu wb, li jx, et al. first case of covid-19 complicated with fulminant myocarditis: a case report and insights. infection. 2020;48(5):7737. 27. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. lancet. 2020;395(10223):497-506. 28. horby p, lim ws, emberson jr, mafham m, bell jl, linsell l, et al. dexamethasone in hospitalized patients with covid-19 preliminary report. n engl j med. 2020. 29. esc. esc guidance for the diagnosis and management of cv disease during the covid-19 pandemic 2020 [available from: https://www.escardio.org/education/covid-19-andcardiology/esc-covid-19-guidance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. kamarullah et al. 6 table 1: clinical studies that reported the use of corticosteroid in management of myocarditis associated with covid-19 authors ( year) age gender complete assessment corticosteroid dose route duration other medication(s) outcome(s) bernaltorres et al. (2020) colombia 38 female fulminant myocarditis associated with covid-19, cardiogenic shock, and covid-19 pneumonia methylprednisolone 200 mg/day iv 12 days intravenous human immunoglobulin, hydroxychloroquine, azithromycin, lopinavir/ritonavir norepinephrine, dobutamine, and levosimendan on first day of admission clinical improvement, discharged on day-16 coyle et al. (2020) usa 57 male myocarditis and severe acute respiratory distress syndrome related to covid-2019 methylprednisolone 500 mg/day iv 4 days hydroxychloroquine, azithromycin, ceftriaxone, colchicine, tocilizumab, milrinone clinical improvement, discharged on day-19 doyen et al. (2020) france 69 male myocarditis associated with covid-19, hypertension hydrocortisone n/a iv 9 days aspirin, fondaparinux clinical improvement, discharged on day-21 garau et al. (2020) belgium 18 female fulminant myocarditis associated with covid-19, cardiogenic shock, and covid-19 pneumonia methylprednisolone 200 mg/day iv 8 days intravenous human immunoglobulin, hydroxychloroquine, antibiotics dobutamine and other vasopressors on first day of admission clinical improvement, discharged on day-45 hu et al. (2020) china 37 male fulminant myocarditis associated with covid-19, cardiogenic shock, and covid-19 pneumonia methylprednisolone 200 mg/day iv 4 days intravenous human immunoglobulin, piperacillin-sulbactam, pantoprazole norepinephrine, diuretic, milrinone clinical improvement, discharged on day-21 hussain et al. (2020) usa 51 male fulminant myopericarditis associated with covid-19, hypertension methylprednisolone n/a iv n/a dobutamine, indomethacin, azithromycin, hydroxychloroquine, remdesivir, colchicine deteriorated after seventh day of admission inciardi et al. (2020) italy 53 female myocarditis associated with covid-19, heart failure methylprednisolone 1 mg/kgbw/day iv 3 days intravenous aspirin, hydroxychloroquine, lopinavir/ritonavir heart failure treatment: canrenone, furosemide, bisoprolol, and dobutamine in the first 48 hours progressive clinical and hemodynamic improvement khalid et al. (2020) usa 34 female myopericarditis associated with covid-19, pericardial effusion, and cardiogenic shock methylprednisolone not specified (high dose) iv + oral 3 days colchine, dobutamine, norepinephrine clinical improvement, discharged on day-9 khatri et al. (2020) usa 50 male purulent myopericarditis associated with covid-19, cardiogenic and distributive shock with multi-organ failure methylprednisolone 200 mg/day iv 2 days dobutamine, vasopressin, norepinephrine, hydroxychloroquine, vancomycin, azithromycin, cefepime, and intravenous human immunoglobulin death due to multi-organ failure li et al. (2020) usa 60 male covid-19-induced myopericarditis, cardiogenic shock, hypertension, hyperlipidemia methylprednisolone 200 mg/day (50 mg/6h) iv 4 days intravenous human immunoglobulin, hydroxychloroquine, azithromycin epinephrine on the first day of admission clinical improvement, discharged on day-52 naneishvili et al. (2020) uk 44 female fulminant myocarditis associated with covid-19 methylprednisolone 1000 mg (1st day) 250 mg/day (2 days) iv 3 days milrinone, norepinephrine clinically improved, echocardiography result improved ortiz et al. (2020) spain 59 female fulminant myocarditis due to covid-19, hypertension, cervical degenerative arthropathy, chronic lumbar radiculopathy, lymph node tuberculosis methylprednisolone 500 mg/d at tapering dose iv 14 days immunoglobulins, antiviral treatment consisting of ifnb, and ritonavir-lopinavir deteriorated with rapid clinical progression to cardiogenic shock. normal biventricular function was regained within a few days, with severe subsequent dyspnea that required continued ecmo richard et al. (2020) usa 28 female fulminant myocarditis associated with covid-19, diabetes mellitus type 1 with multiple previous episode of diabetic ketoacidosis, diabetic gastroparesis, asthma, anxiety, depression methylprednisolone 1 g/day iv 3 days dobutamine, norepinephrine, heparin, insulin, potassium, vancomycin, and piperacillin-tazobactam clinically improved on the third day following corticosteroid administration salamanca et al. (2020) spain 44 male fulminant myocarditis associated with covid-19, cardiogenic shock methylprednisolone 1000 mg iv 1 day tocilizumab, hydroxychloroquine, azithromycin, and lopinavir-ritonavir. clinical status improved sampaio et al. (2020) brazil 45 female fulminant myopericarditis associated with covid-19, cardiac tamponade, and refractory circulatory shock methylprednisolone 750 mg and 250 mg (1st and 2nd day) followed by 40 mg twice a day) iv 2 days tocilizumab, intravenous human immunoglobulin, convalescent plasma, azithromycin, piperacillin/tazobactam, and teicoplanin noradrenaline, dobutamine, milrinone and vasopressin. clinical improvement, discharged on day-65 shabbir et al. (2020) uk 50 female covid-19-induced myopericarditis, myositis, hypertension, reactive arthritis prednisolone 30 mg oral 12 days ibuprofen, codeine phosphate, colchicine clinical improvement, discharged on day-13 tavares et al. (2020) usa 61 male fulminant myocarditis associated with covid-19 and cardiogenic shock methylprednisolone not specified (high dose) iv n/a norepinephrine, furosemide, cefepime, doxycycline, hydroxychloroquine, enoxaparin death zeng et al. (2020) china 63 male fulminant myocarditis associated with covid-19, severe pneumonia, ards, and multiple organ dysfunction syndrome (mods) methylprednisolone n/a n/a n/a lopinavir–ritonavir, interferon α-1b, immunoglobulin, piperacillin–tazobactam the patient died on the 33rd day of hospitalization abbreviations: kgbw: kilogram body weight; n/a: not available; ecmo: extracorporeal membrane oxygenation; iv: intravenous; ards: acute respiratory distress syndrome. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e32 table 2: assessment of the risk of bias of the included studies authors were patient’s demographic characteristics clearly described? was the patient’s history clearly described and presented as a timeline? was the current clinical condition of the patient on presentation clearly described? were diagnostic tests or assessment methods and the results clearly described? was the intervention(s) or treatment procedure(s) clearly described? was the postintervention clinical condition clearly described? were adverse events (harms) or unanticipated events identified and described? does the case report provide takeaway lessons? total risk of bias bernal-torres et al. yes yes yes yes yes yes unclear yes 87.5% low coyle et al. yes yes yes yes yes yes unclear yes 87.5% low doyen et al. yes yes yes yes unclear yes no yes 75% low garau et al. yes yes yes yes yes yes unclear yes 87.5% low hu et al. yes yes yes yes yes yes no yes 87.5% low hussain et al. yes no yes yes no yes unclear yes 62.5% low inciardi et al. yes yes yes yes yes yes yes yes 100% low khalid et al. yes yes yes yes unclear yes yes yes 87.5% low khatri et al. yes yes yes yes yes yes yes yes 100% low li et al. yes yes yes yes yes yes unclear yes 87.5% low naneishvili et al. yes yes yes yes yes yes unclear yes 87.5% low ortiz et al. yes yes yes yes yes yes yes yes 100% low richard et al. yes yes yes yes yes yes unclear yes 87.5% low salamanca et al. yes yes yes yes yes yes unclear yes 87.5% low sampaio et al. yes yes yes yes yes yes unclear yes 87.5% low shabbir et al. yes yes yes yes yes yes no yes 87.5% low tavares et al. yes yes yes yes unclear yes no yes 75% low zeng et al. yes yes yes yes unclear yes yes yes 87.5% low all articles were published in 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. kamarullah et al. 8 figure 1: flow chart of study selection. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e59 or i g i n a l re s e a rc h effect of queue management system on patient satisfaction in emergency department; a randomized controlled trial ali bidari1, shabahang jafarnejad1, nazanin alaei faradonbeh1∗ 1. emergency medicine department, iran university of medical sciences, tehran, iran. received: july 2021; accepted: august 2021; published online: 5 september 2021 abstract: introduction: patients’ experience in hospitals affects their satisfaction. the purpose of the present study was to assess the effect of applying a queue management system on patient satisfaction in emergency department waiting rooms. methods: the present prospective randomized single-blinded interventional study was performed from july to august 2020 and involved 236 patients that were divided into one intervention group and one control group, each consisting of 118 patients. the mentioned patients’ perception of the waiting time and satisfaction before being visited by an emergency medicine doctor was evaluated with and without applying the queue management system. results: the mean actual waiting time (15.5 ± 7.5 minutes) as well as the mean perceived waiting time (11.9 ± 7.4 minutes) for the intervention group were significantly lower than those of the control group with the values of 27.03 ± 8.5 and 32.8 ± 8.7 minutes, respectively (p < 0.001). the mean perceived waiting time was significantly less than the mean actual waiting time (11.9 min vs 15.5 minutes) for the intervention group (p <0.001); however, the mean perceived waiting time was significantly higher than the mean actual waiting time (32.8 vs 27.03 minutes) for the control group (p < 0.001). the level of satisfaction in the intervention group was significantly higher than that of the control group (p <0.001). there was an inverse relationship between the actual waiting time (intervention group: r=-0.463; control group: r= -0.567) and the perceived waiting time (intervention group: r= -0.439; control group: r= -0.568) with the satisfaction level in both groups (p < 0.001). conclusion: it can be proposed that the application of a queue management system in the emergency department waiting rooms can reduce the actual and perceived waiting times and increase the patient satisfaction. keywords: emergency service, hospital; patient satisfaction; waiting rooms; pediatric emergency medicine cite this article as: bidari a, jafarnejad s, alaei faradonbeh n. effect of queue management system on patient satisfaction in emergency department; a randomized controlled trial. arch acad emerg med. 2021; 9(1): e59. https://doi.org/10.22037/aaem.v9i1.1335. 1. introduction patient satisfaction has transpired as a progressively important issue in health care and is currently used for four associated but different purposes: 1) to measure the quality of care, 2) to evaluate various health care programs or systems, 3) to help organizations notice consumers that are likely to deregister, and 4) to recognize which aspects of a service require improvements to increase patient satisfaction (1). from the early 1990s, research on patients’ satisfaction ∗corresponding author: nazanin alaei faradonbeh; emergency medicine department, iran university of medical sciences, tehran, iran. email: nazanin.alaie@gmail.com, tel: 0098-913-129-8388, orcids: https://orcid.org/0000-0003-4829-5154. with emergency care has steadily extended, and many studies have employed a multivariate analytical scheme to point out parameters that mostly anticipate the overall satisfaction in this regard (2). waiting time has been weighed as a significant determinant of patient satisfaction. increased waiting time adds to indirect costs of taking part in an emergency department (ed) encounter from the patients’ perspective. in addition, the prolonged waiting time may increase patient disappointment and reduce their sense of control/patience (3). hence, prognosticators of patient satisfaction in eds are of great significance. concentrating on accurate prognosticators may be crucial to sustain current patients and attract potential new ones. strategic resolutions in this field may also affect the financial suitability of health care institutions (4). the movement of patients through a healthcare facility from this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bidari et al. 2 the point of admission to the point of discharge, which is known as the patient flow, is a critical component of process management in eds that involves medical care, physical resources, and internal systems, as well as maintaining patient satisfaction and quality of care. improvement of patient flow in eds via the application of a queue management system enables efficient handling of resources and patient queues so that patients receive the right care at the right time in a convenient and trouble-free environment. from patient check-in to patient calling and appointment, queue management systems allow the staff to excellently manage patient waiting times and organize the entire patient flow in eds (2-4). an ed visit frequently yields the first and the only impression that patients have with respect to an institution and can markedly shape their post-visit sensations and future reactions (5). furthermore, a satisfied patient departs from the hospital with a positive impression and is less likely to complain or file suits against the institution (6). in addition to these marketing roots, patient satisfaction has been indicated to increase with discharge instructions. therefore, physicians can positively influence their patients’ outcomes following the ed visit by warranting the patient satisfaction (7). queue management system is used to streamline patient flow through hospitals and clinics. using these systems patients won’t have to wait longer than its necessary, and they can join the que virtually, from anywhere, using sms, social media, a smartphone app, or a website booking system. there are two types of waiting time: 1) the actual time between the patient entering the emergency room and the physician visiting them. 2) the perceived time between the patient entering the emergency room and the physician visiting them. as service providers, we need to consider both types of waiting time. if we reduce the actual waiting time while enhancing the perceived waiting time, we can improve the patients’ experience. due to the importance of emergency management and patient satisfaction, conditions should be prepared to create a proper and regular queuing system so that patients’ waiting time is adjusted and reduced. therefore, the present study assessed the effect of applying a queue management system on patient satisfaction in ed waiting rooms. 2. methods 2.1. study design and setting this prospective a single-blinded randomized trial was conducted in hazrat-e-ali-asghar hospital affiliated to iran university of medical sciences, tehran, iran, in 2020 to measure the satisfaction of sick children from their parents’ perspective. the patients’ perception of the waiting time and satisfaction before being visited by an emergency medicine doctor was evaluated with and without applying the queue management system. this study was approved by the ethics committee of iran university of medical sciences under the code ir.iums.fmd.rec.1398.156. accordingly, written informed consent was taken from all parents before any intervention. 2.2. participants the study sample for this prospective study consisted of all pediatric patients with the emergency severity index of 4 and 5 that presented to the ed during the randomly-selected shifts over 2 months ( july-august) in 2020. in all pediatric cases, sick children were the main recipients of health care; however, service providers still required the attention and participation of parents. patients that were randomly selected from the patients that referred to the ed of our hospital. a randomized blocking (block size of four) method was applied using a computergenerated random number list prepared by an investigator with no clinical involvement in the trial. eligible patients were randomly divided into two groups of one hundred eighteen using random blocks. this sample size was calculated using the sample size formula for comparing two means. also, we excluded patients who presented to the ed with severity index of 1, 2, and 3. each patient was examined by at least one of the attending emergency physicians, residents, or interns. the staff of the ed of our hospital included attending emergency medicine and pediatric physicians, emergency medicine and pediatric residents, and interns who rotated through the ed for a one-month period. 2.3. blinding and intervention this study was single-blinded: the patients and their parents were not aware of the course of the intervention. the researcher and clinicians were informed of the allocation in the intervention group. the queue management system employed in the ed of our hospital intervened in the queue length management. the intervention group consisted of patients whose entrance to the triage room until their first visit by a physician was managed using this system. the control group consisted of patients that this system was not used for them but were otherwise under the same conditions as the intervention group. to perform this study, during two months ( july-august) in 2020 we randomly selected half of the days and in those days, we used the queue management system. therefore, patients who came on those specific days were entered to the intervention group. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e59 table 1: comparing the chief complaints, parents’ stress, and satisfaction levels between cases handled with (a) and without (b) queue management system variable group a group b p number percent number percent chief complaints fever 47 39.8 51 43.2 respiratory 2 1.7 7 5.9 gastrointestinal 29 24.6 25 21.2 0.34 urinary 4 3.4 6 5.1 others 36 30.5 29 24.6 stress level no stress 0 0 0 0 low 0 0 4 3.4 moderate 28 23.7 26 22 0.41 high 48 40.7 52 44.1 extreme 42 35.6 36 30.5 satisfaction level very poor 0 0 1 0.8 poor 0 0 11 9.3 average 0 0 54 45.8 < 0.001 good 16 13.6 49 41.5 excellent 102 86.4 3 2.5 2.4. outcomes and measurements in this study, measuring parents’ satisfaction level was defined as the primary outcome. to measure these values, the actual waiting time and the perceived waiting time measured from the patient’s entrance to the triage room until their visit by a physician were recorded in minutes. secondary outcomes were comparing the parent’s stress level, and child’s demographic information and chief complaint between the intervention and control groups. moreover, patients’ chief complaints were categorized based on the frequency distribution of symptoms including fever, respiratory, gastrointestinal, urinary, and other symptoms. 2.5. data collection the data were collected by observation and asking questions; all were gathered in checklists and then recorded in the data bank. also, parents’ stress and satisfaction levels were also collected using the checklists based on a likert scale ranging from 1 for very poor to 5 for very good. we didn’t have any missing data in our study. 2.6. statistical analysis the data were entered into the statistical analysis software, spss, version 25, and then statistically analyzed. kolmogorov-smirnov test was used to assess the normality of data distribution. all descriptive data had normal distribution. therefore, the results for the quantitative variables were reported in mean ± standard deviation (sd) format and the ordinal qualitative variables were reported in frequency and percentages. for comparing quantitative and qualitative variables, the mann-whitney u, student’s t test or chi-square test were used. p values <0.05 were considered statistically significant. 3. results two hundred thirty six patients were assessed (118 patients in each of the control and intervention groups were studied; 58.5% male). the mean age of children in the intervention and control groups was 3.6 ± 2.3 and 3.4 ± 1.8 years, respectively (p = 0.57). distribution of symptoms was not significantly different between intervention and control groups (p = 0.34; table 1). there was no significant difference between the two groups in terms of the parents’ stress level on arrival (p = 0.41). the mean actual waiting time (15.5 ± 7.5 minutes) as well as the mean perceived waiting time (11.9 ± 7.4 minutes) for the intervention group were significantly lower than those of the control group with the values of 27.03 ± 8.5 and 32.8 ± 8.7 minutes, respectively (p < 0.001). the mean perceived waiting time was significantly less than the mean actual waiting time (11.9 min vs 15.5 minutes) for the intervention group (p <0.001); however, the mean perceived waiting time was significantly higher than the mean actual waiting time (32.8 vs 27.03 minutes) for the control group (p < 0.001). the level of satisfaction in the intervention group was significantly higher than that of the control group (p <0.001). moreover, none of the parents reported a very poor, poor, or even this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bidari et al. 4 average level of satisfaction in the intervention group (all had good and excellent levels of satisfaction; table 1). there was an inverse relationship between the actual waiting time (intervention group: r=-0.463; control group: r= 0.567) and the perceived waiting time (intervention group: r= -0.439; control group: r= -0.568) with the satisfaction level in both groups (p < 0.001). in other words, the level of satisfaction decreased with increase in the waiting time. 4. discussion the findings of this study revealed that application of a queue management system resulted in the decreased perceived waiting time and also the actual waiting time. the presented findings confirm that application of a queue management system could significantly increase the level of satisfaction in the intervention group. an inverse relationship was observed between the actual waiting time and the perceived waiting time with the level of satisfaction. most of the parents experienced moderate to extreme stress levels on their arrival at the ed. it is important to consider the demographic properties of the patients, or their parents in the pediatric field, while evaluating the perception of time and their satisfaction (8). franck et al. stated that parental stress was not related to their age, race, or job satisfaction. in contrast, parental stress was independently related to their estimation of pain, the management technique, and the correct information provided by the health care staff about the techniques used for children’s pain reduction and treatment (9). other studies have also shown that the satisfaction of the patients is not related to their demographic properties or their illness perception. however, the waiting time can affect their satisfaction, significantly (10). eight principles can be employed by organizations to affect the customer satisfaction during the waiting time. based on the presented principles, the waiting time that is not filled with a specific schedule, the waiting time that elapses before offering the treatment, the waiting time accompanied with anxiety, the waiting time for an indefinite period, the waiting time for no apparent reason, the unfair waiting time, and waiting alone seem longer than the actual waiting time. however, the recipient of the service endures a longer waiting time in exchange for receiving a service with a higher value (11). the study of spechbach and colleagues in 2019 suggests that there is a golden hour window for patients, which is the time they can wait for receiving medical service. difference of the triage level with their personal assessment of their condition, having a feeling of being forgotten, ambiguity of the situation, and the lack of sense of privacy were the most important factors, affecting the perceived waiting time in patients in that study (12). studies suggest that more than 75%, 68%, and 41% of the patients, regardless of their gender and chief complaint, overestimate their waiting time for triage, after triage, and their total time spent in ed (13). it is shown that young patients and those with less prior ed admission history have more accurate estimations of their waiting time. patients with longer waiting in the triage also are shown to have overestimations, in comparison with those with longer waiting in the examination room. therefore, waiting for an indefinite time in the control group of the present study caused a longer perceived time for this group. moreover, it seems that applying a queue management system resulted in a more organized atmosphere in the ed waiting room as the actual waiting time was reduced for the intervention group. whiting et al. worked on the gap between actual and perceived waiting times and stated that as the gap extends, the satisfaction decreases. furthermore, as the actual waiting time increases, the waiting gap decreases. furthermore, although expectations with regard to receiving a service do not affect the waiting gap, they can affect the level of satisfaction. finally, the higher the applicants’ anxiety, the higher the expectation gap will be (14). the level of satisfaction decreases with increase in the waiting time. besides, filling the waiting time with fun activities increases the applicants’ satisfaction; however, informing the applicants of the waiting time duration, despite increasing their perception of waiting time, does not affect their satisfaction (15). the perceived waiting time was, on average, one minute longer than the actual waiting time, and waiting for five minutes or less to receive the service was reasonable for the applicants (15). in contrast, the findings of the current study indicated that the mean perceived waiting time in the intervention group was 3.6 minutes less than the mean actual waiting time, and the mean perceived waiting time was 5.8 more than the mean actual waiting time in the control group. furthermore, the study conducted by hui et al. showed that the acceptance of waiting and the manner of response to the waiting time affected applicants’ perception and service evaluation but had no effect on their perceived time. in addition, none of the waiting time-related information pieces applied to the shortterm waiting. however, the information related to the waiting time, as compared with the general information, had a greater effect on the average perception of the waiting time in the medium-term waiting time but a lower effect on the average perception of the waiting time in the long-term waiting time (16). the study of carr and colleagues has revealed that the patients suffer from the ambiguity and uncertainty of their condition, while waiting for the doctor or their surgery (17). reassuring the patient and his/her company about his condition can be a satisfying factor, decreasing the perceived this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e59 waiting time. it should be noted that the perceived time can be influenced by various factors. even the perceived time for waiting at the red light can be altered with the tempo of the auditory signal, played at the time of the waiting period (18). the condition can be more complicated in a complex situation such as waiting in the ed. further studies are needed to identify and control these potentially confounding factors. the medical status of the patient, their age, gender, past medical history, and their location in the ed are potential confounders (13, 19). queue management system is especially valuable in developing countries, because the application of the queue management system is not a routine intervention in developing countries (in contrast to developed countries) while it is affordable and suitable for their crowded eds. these types of research-based interventions are required in fields such as clinical care processes, nursing services, and para-clinical services after the ed admission. to observe signs of progress, institutionalization of the quality management in health services is a must, and utilization of the obtained feedback can systematically enhance the efficiency and patient satisfaction in the eds. also, we can use this system in the adult emergency department and enhance that place. therefore, we need to do more research on this topic. 5. limitations this research was subject to several limitations. the first limitation was related to its conduction in a single center with a small number of participants. the second limitation was related to the single-blinded nature of the study. moreover, although the researchers tried to control the effect of other aspects of this study on the data, it was possible that applying a queue management system affected the triage nurses’ behavior toward the patients’ family. we had some biases and confounding conditions such as lack of time to accurately enter data to checklist or the fatigue of physicians and interns while visiting and talking to the patients. also, how the ed staff talks and behave in front of parents affects the answers to questions on the checklists. 6. conclusion the findings of this study revealed that with regards to providing the optimal ed services and gaining patients’ satisfaction, the application of a queue management system can result in a remarkable change in the health care system as it affects the actual and perceived waiting times. 7. declarations 7.1. acknowledgments the authors would like to express their deepest appreciation to the hazrat-e-ali-asghar pediatric hospital emergency department’s staff for their valuable cooperation. 7.2. funding and supports none declared. 7.3. author contribution study concept and design, acquisition of the data: ali bidari, shabahang jafarnejad analysis and interpretation of the data: shabahang jafarnejad, nazanin alaei faradonbeh drafting of the manuscript: nazanin alaei faradonbeh critical revision of the manuscript for important intellectual content: ali bidari, statistical expertise: ali bidari, nazanin alaei faradonbeh acquisition of funding: none. 7.4. competing interest none declared. 7.5. consent for publication not applicable. 7.6. availability of data and materials the datasets used and analyzed in the current study are available from the corresponding author on reasonable request. references 1. jackson jl, chamberlin j, kroenke k. predictors of patient satisfaction. social science & medicine. 2001;52(4):609-20. 2. boudreaux ed, d’autremont s, wood k, jones gn. predictors of emergency department patient satisfaction: stability over 17 months. academic emergency medicine. 2004;11(1):51-8. 3. thompson da, yarnold pr, williams dr, adams sl. effects of actual waiting time, perceived waiting time, information delivery, and expressive quality on patient satisfaction in the emergency department. annals of emergency medicine. 1996;28(6):657-65. 4. hostutler jj, taft sh, snyder c. patient needs in the emergency department: nurses’ and patients’ perceptions. jona: the journal of nursing administration. 1999;29(1):43-50. 5. brown ad, sandoval ga, levinton c, blackstien-hirsch p. developing an efficient model to select emergency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. bidari et al. 6 department patient satisfaction improvement strategies. annals of emergency medicine. 2005;46(1):3-10. 6. rydman rj, roberts rr, albrecht gl, zalenski rj, mcdermott m. patient satisfaction with an emergency department asthma observation unit. academic emergency medicine. 1999;6(3):178-83. 7. trout a, magnusson ar, hedges jr. patient satisfaction investigations and the emergency department: what does the literature say? academic emergency medicine. 2000;7(6):695-709. 8. xie z, or c. associations between waiting times, service times, and patient satisfaction in an endocrinology outpatient department: a time study and questionnaire survey. inquiry: the journal of health care organization, provision, and financing. 2017;54:0046958017739527. 9. franck l, cox s, allen a, winter i. 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field study. journal of services marketing. 2009. 15. larson r, larson b, katz k. prescription for waiting–in line blues: entertain, enlighten and engage. sloan management review,(winter). 1991;32(2):44-55. 16. hui mk, zhou l. how does waiting duration information influence customers’ reactions to waiting for services? 1. journal of applied social psychology. 1996;26(19):1702-17. 17. carr t, teucher uc, casson ag. time while waiting: patients’ experiences of scheduled surgery. qualitative health research. 2014;24(12):1673-85. 18. cao y, zhuang x, ma g. shorten pedestrians’ perceived waiting time: the effect of tempo and pitch in audible pedestrian signals at red phase. accident analysis & prevention. 2019;123:336-40. 19. rankin k, sweeny k, xu s. associations between subjective time perception and well-being during stressful waiting periods. stress and health. 2019;35(4):549-59. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e68 rev i ew art i c l e screening performance characteristics of ultrasonography in confirmation of endotracheal intubation; a systematic review and meta-analysis mehrdad farrokhi1∗, bardia yarmohammadi2, amir mangouri3, yasaman hekmatnia4, yaser bahramvand5, moein kiani6, elham nasrollahi5, milad nazari-sabet7, niusha manoochehri-arash8, maria khurshid9 †, shima mosalanejad10, vida hajizadeh11, reza amani-beni12, masoumeh moallem13, maryam farahmandsadr14 1. eris research institute, tehran, iran. 2. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of vascular and endovascular surgery, sina hospital, tehran university of medical sciences, tehran, iran. 4. islamic azad university, sari branch, school of medicine, sari, iran. 5. school of medicine, shiraz university of medical sciences, shiraz, iran. 6. school of medicine, zanjan university of medical sciences, zanjan, iran. 7. department of general surgery, school of medicine, isfahan university of medical sciences, isfahan, iran. 8. endocrine research center, research institute for endocrine sciences, shahid beheshti university of medical sciences, tehran, iran. 9. department of internal medicine, berkshire medical center, pittsfield, massachusetts, usa. 10.department of internal medicine, faculty of medicine, tehran medical sciences, islamic azad university, tehran, iran. 11.school of dentistry, shiraz university of medical sciences, shiraz, iran. 12.school of medicine, isfahan university of medical sciences, isfahan, iran. 13.department of emergency medicine, school of medicine, tehran medical sciences branch, islamic azad university, tehran, iran. 14.school of medicine, jahrom university of medical sciences, jahrom, iran. received: august 2020; accepted: september 2021; published online: 26 october 2021 abstract: introduction: recent studies have suggested that point-of-care ultrasonography can be used for confirming the placement of endotracheal tube. this systematic review and meta-analysis aimed to investigate the sensitivity and specificity of ultrasonography for confirming endotracheal tube placement. methods: in this meta-analysis, systematic search of the previous published papers investigating the diagnostic accuracy of ultrasonography for confirmation of endotracheal tube placement was performed. seven electronic databases, including pubmed, scopus, google scholar, ebsco, embase, web of science, and cochrane database were searched up to july 2021, for all relevant articles published in english on this topic. meta-disc version 1.4 software was used for statistical analysis. results: the estimated pooled sensitivity and specificity of ultrasonography for confirmation of endotracheal tube location were 0.98 (95% ci: 0.98–0.99) and 0.94 (95% ci 0.91–0.96), respectively. the pooled positive likelihood ratio and negative likelihood ratio were 5.94 (95% ci 4.41–7.98) and 0.03 (95% ci: 0.02-0.04), respectively. the diagnostic odds ratio of ultrasonography was 281.47 and the area under hierarchical summary receiver operating characteristic (hsroc) revealed an appropriate accuracy of 0.98. conclusion: ultrasonography has high diagnostic accuracy and can be used as a promising tool for confirmation of endotracheal tube placement, especially in critically ill patients or when capnography is not available, or its result is equivocal. keywords: airway management; intubation; meta-analysis; sensitivity and specificity; ultrasonography cite this article as: farrokhi m, yarmohammadi b, mangouri a, hekmatnia y, bahramvand y, kiani m, nasrollahi e, nazari-sabet m, manoochehri-arash n, khurshid m, mosalanejad s, hajizadeh v, amani-beni r, moallem m, farahmandsadr m. screening performance characteristics of ultrasonography in confirmation of endotracheal intubation; a systematic review and meta-analysis. arch acad emerg med. 2021; 9(1): e68, https://doi.org/10.22037/aaem.v9i1.1360. ∗corresponding author: mehrdad farrokhi; eris research institute, tehran, iran. email: dr.mehrdad.farrokhi@gmail.com, phone number: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 2 1. introduction securing a definitive airway in critically ill patients is a necessary procedure performed in intensive care unit (icu), out of hospital, and in the emergency department (ed) settings. direct assessment of the endotracheal tube passage through the cords is commonly performed via primary localization, followed by a confirming method (1, 2). however, direct visualization of endotracheal tube passing through the cord may be misleading during difficult intubations, which may lead to esophageal intubation in emergency cases. unrecognized esophageal intubations are associated with catastrophic consequences such as neurological complications or death. therefore, different techniques are often used to confirm the appropriate placement of endotracheal tube, but not all of them are all of them are not reliable enough to confirm the tracheal intubation (3, 4). it has been suggested that both clinical evaluations and confirmatory methods including auscultation, chest expansion following ventilation, bronchoscopy, chest x-ray, capnography, and end-tidal carbon dioxide (etco2) assessment should be used to confirm the location of endotracheal tube. in this regard, etco2 has not been suggested for patients with cardiac arrest or embolism. similarly, capnography has some limitations, including low reliability in patients with embolism or cardiac arrest, or recent bag-valve-mask use (5-7). due to the abovementioned limitations, combined with growing application of ultrasound by emergency medicine (em) physicians and ease of use of point-of-care ultrasonography, many studies have been performed to assess the reliability of ultrasonography for approving the placement of endotracheal tube. however, most of these investigations had small sample sizes with different gold standards, resulting in conflicting findings. accumulating lines of evidence have recently suggested that point-of-care ultrasonography can be used as an adjunct for confirming the placement of endotracheal tube, especially in critical situations such as cardiac arrest or when other confirmation methods are not available (8-10). however, before approval of ultrasonography as a promising technique for confirmation of endotracheal tube placement, it is necessary to pool the results of previously published studies. therefore, in this systematic review and meta-analysis, we aimed to assess the screening performance characteristics of ultrasonography in confirmation of endotracheal tube place+989384226664. † corresponding author: maria khurshid; department of internal medicine, berkshire medical center, pittsfield, massachusetts, usa. email: drmkhurshid@yahoo.com. ment. 2. methods 2.1. data sources and searches we performed a systematic search of the previous published papers investigating the diagnostic accuracy of ultrasonography for confirmation of endotracheal tube placement. we searched pubmed, scopus, google scholar, ebsco, embase, web of science, and cochrane databases from inception to july 2021. the systematic search was carried out using medical subject heading (mesh) terms for ”ultrasonography” and ”intubation”. in this regard, we used ”sono”, ”sonography”, ”ultrasonography”, ”ultrasound”, ”endotracheal intubation”, ”esophageal intubation”, and ”intubation”. our search had no restrictions with respect to location of study or publication date. furthermore, in this meta-analysis, we only assessed human studies. 2.2. selection criteria in this meta-analysis we included studies investigating the diagnostic accuracy of bedside ultrasound to confirm endotracheal tube placement following emergency or elective intubation in adult subjects. the included studies were required to compare the findings of ultrasonography with a gold standard technique, such as fiberoptic bronchoscopy or capnography, for confirmation of endotracheal tube placement. retrospective design studies, case reports, case series, and reviews were excluded and clinical trials, case-control or cohort design studies were included in this study. investigations performed using mannequins, cadavers, or pediatric patients were excluded from the study. two independent reviewers (m.f and b.y) assessed the studies according to the above-mentioned criteria and any discrepancy between them was resolved by a third reviewer (m.k). in order to avoid possible duplicates, we searched the first author’s name, as well as the place and the period of the subjects’ enrolment. in the case of different versions of the same study, only the most recent was considered. 2.3. data extraction data were extracted by two reviewers and included characteristics of the studies (the first author, publication date, sample size, male percentage, mean age of participants, and location of intubation), ultrasonic technique, transducer type, percentage of esophageal intubation, gold standard for confirmation of endotracheal tube placement, and diagnostic accuracy parameters of ultrasonography (number of true positive, true negative, false positive, and false negative). the process of data extraction was performed by two investigators independently and finally, inconsistencies regarding included studies were resolved by a third reviewer. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e68 2.4. data synthesis meta-disc version 1.4 software and comprehensive metaanalysis software version 3 were used for statistical analysis. the heterogeneity among the included studies was investigated using q-statistic and i2 index. if the value of i2 was higher than 50% or p-value was less than 0.10, the random model was used to estimate the sensitivity and specificity of ultrasonography for confirmation of endotracheal tube placement. alternatively, if the value of i2 was less than 50% and p-value was higher than 0.10, the sensitivity and specificity of ultrasonography were calculated using fixed model. egger’s test and funnel plot were used to evaluate publication bias. 3. results 3.1. search results figure 1 summarizes the flow of studies in this review according to preferred reporting items for systematic reviews and meta-analyses (prisma) recommendations. a total of 9542 studies were identified in our preliminary search. after removal of 1682 duplicates, abstracts of the remaining 7860 studies were assessed by two independent reviewers (m.f and b.y). the full-text of 142 articles were evaluated for eligibility and 107 article were excluded according to the exclusion criteria. finally, 33 articles evaluating 2840 patients were included in our meta-analysis. 3.2. characteristics of included studies the characteristics of the 33 included studies are summarized in table 1. studies were performed between 2007 and 2020, with the sample sizes ranging from 19–150 subjects. most of the included studies were performed in iran (seven studies). twenty-nine studies were prospective observational studies and 4 were controlled trials. five studies were conducted in icus, 10 were performed in operating rooms, and 18 were carried out in eds. the prevalence of esophageal intubation was estimated to be 8.4% (95% ci: 6.5-10.8; figure 2). 3.3. publication bias and quality assessment assessment of publication bias based on egger’s test showed that there was a statistically significant publication bias (p<0.01). moreover, the funnel plot of included studies revealed significant asymmetry (figure 3). quality assessment of the included studies was performed using quadas-2 tool (table 2). 3.4. diagnostic accuracy indices the estimated pooled sensitivity and specificity of ultrasonography for confirmation of endotracheal tube location were 0.98 (95% ci: 0.98–0.99) and 0.94 (95% ci 0.91–0.96), respectively (figure 4 and figure 5). the pooled positive likelihood ratio and negative likelihood ratio were 5.94 (95% ci 4.41–7.98) and 0.03 (95% ci: 0.02-0.04), respectively (figure 6 and figure 7). furthermore, the diagnostic odds ratio of ultrasonography was 281.47 (95% ci: 168.91–469.06) (figure 8). the area under hierarchical summary receiver operating characteristic curve (hsroc) revealed an appropriate accuracy of 0.98 (figure 9). subgroup analysis based on transducer type and location of intubation (icu or ed, or operating room) showed acceptable sensitivity and specificity. 4. discussion the results showed that the estimated pooled sensitivity and specificity of ultrasonography for confirmation of endotracheal tube location were 0.98 and 0.94, respectively. the diagnostic odds ratio of ultrasonography was 281.47 and the area under hsroc revealed an appropriate accuracy of 0.98. our findings confirm the efficacy of ultrasonography as an adjunct for assessment of endotracheal tube location during intubation. it should be noted that these results are important since capnography has been considered to have low accuracy, especially in subjects with critical conditions. similarly, ultrasonography has been approved by advanced cardiac life support guidelines as an adjunct for capnography to confirm endotracheal tube placement (11). furthermore, most confirmatory techniques need some ventilation, which is associated with higher rates of aspiration and gastric distention in cases with wrong location of endotracheal tube (5, 12). on the other hand, ultrasonography does not increase risk of aspiration or gastric distention and has some advantages including being available in different locations, noninvasive, and rapid for confirmation of endotracheal tube placement. in a similar study, adhikari et al. (13) have performed a systematic search in different databases to identify studies evaluating efficacy of ultrasonography for confirmation of endotracheal tube placement. their systematic search yielded 5 eligible studies. in this study, the authors estimated 91% sensitivity (95% ci, 74% to 97%) and 97% specificity (95% ci, 89%to 99%) for ultrasonography, which are lower than those found in our study. in another study, a systematic search was carried out in embasetm, medline, lilacs, the cochrane library, koreamed, opengrey, and the world health organization international clinical trials registry from their inception to 2014, which yielded 11 studies with 969 patients (14). they reported pooled sensitivity and specificity of ultrasonography in confirming the placement of the tube as 0.98 and 0.98, respectively. although their estimated pooled sensitivity was similar to that found in our study, their pooled specificity was higher than ours. these differences can partially be exthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 4 plained by the difference in the number of included studies, sample sizes of patients, and also causes of patient hospitalization. although our findings confirmed the efficacy of ultrasonography as a promising adjunct for confirmation of endotracheal tube placement, it should be noted that there are some significant limitations for ultrasonography. first, the efficacy of ultrasonography is dependent on the operator and ultrasonography by different operators may result in different ultrasonographic image qualities and decisions. therefore, ultrasonography operators must obtain necessary skills before performing ultrasonography for confirmation of endotracheal tube location. furthermore, ultrasonography cannot be performed easily in situations where there is only one operator, because that operator may be the technician performing endotracheal intubation. therefore, in these cases, the static techniques is superior to dynamic technique. moreover, the placement of ultrasonographic transducer on the trachea when a tube is entering the trachea may be associated with a more difficult intubation as it might deviate its path. in this regard, it has been suggested that the pressure of transducer on trachea should be reduced by ultrasonography operator to prevent deviation of endotracheal tube during intubation. if ultrasonography increases the risk of difficult intubation, the procedure should be performed using static technique. from another point of view, ultrasonography may be difficult for some intubations including cases with different airway anatomy, neck edema, cervical collar, subcutaneous emphysema, and neck masses. unlike ultrasonography, capnography requires four to five ventilations to confirm the location of endotracheal tube placement, so ultrasonography is faster than capnography. however, the efficacy of capnography is not dependent on the experience of operator and training does not affect the accuracy of this method (15). it is now well established that ultrasonography has several strong points for confirmation of endotracheal tube location. deviation of endotracheal tube into the esophagus can be easily identified before initiation of ventilation because ultrasonography is carried out in real time during intubation. since ultrasonography has an appropriate specificity for identification of esophageal intubation, this method can be used in cases with indefinite result of capnography to reduce the total number of intubation attempts. furthermore, ultrasonography does not interfere with chest compression and intubation can be performed during cardiopulmonary resuscitation. however, further studies with larger sample sizes using appropriate gold standards are required to establish ultrasonography as a promising diagnostic test for assessment of 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administrative data on injuries resulting from car accidents in shiraz, iran: 2011–2014 data. chinese journal of traumatology english edition. 2017;20(1):27-33. 33. yousefzadeh-chabok s, razzaghi a. the relationship between socio-economic status and the consequences of deathes and injury severity in road traffic crash patients. iran occupational health. 2019;16(2):1-10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e68 table 1: characteristic of studies included in the meta-analysis author year sample size location mean age male (%) ultrasonic technique transducer type esophageal intubation (%) gold standard chowdhury et al. (3) 2020 120 or 39.02 28 dynamic linear 4.1 cap+a chen et al. (1) 2020 118 icu 71.5 60.2 dynamic nr 10.2 dv+fb men et al. (16) 2019 68 or 60.4 54 static curvilinear 17.6 a+fb patil et al. (17) 2019 91 icu nr nr dynamic linear 2 cap afzalimoghadam et al. (18) 2019 90 ed 59.2 58.9 dynamic linear 3.3 cap zamani et al. (19) 2018 100 ed 57.5 73 dynamic linear 6 cap kad et al. (20) 2018 100 or nr nr static linear 2 a et al. (21) 2018 40 icu 55.7 65 dynamic curvilinear 10 fb inangil et al. (22) 2018 50 or 42.9 56 dynamic linear 6 cap arya et al. (23) 2018 75 icu 63.4 55.3 dynamic linear 16 cap arafa et al. (24) 2018 107 or 41.4 63.6 dynamic linear 7.5 cap zamani et al. (25) 2017 150 ed 58.5 56 static linear 11.3 o+as+dv+a yang et al. (26) 2017 93 or 53.5 46 static linear 9.7 cap+a thomas et al. (27) 2017 100 ed 50.8 59 static linear 5 cap rahmani et al. (28) 2017 75 ed 61.1 62.7 dynamic linear 0 dv masoumi et al. (8) 2017 100 ed 64.5 65 static curvilinear 6 cap lahham et al. (9) 2017 72 ed 57.7 56.9 dynamic linear 4.2 cap abhishek et al. (5) 2017 100 or 38.9 nr static linear 5 cap khosla et al. (29) 2016 20 icu 70.5 100 static linear 0 cap+a karacabey et al. (a) (10) 2016 85 ed 67.2 nr dynamic linear 38.2 cap karacabey et al. (b) (10) 2016 30 ed nr nr dynamic linear nr cap abbasia et al. (30) 2015 120 ed 50 61.5 dynamic/static linear 11.7 dv+a+cap sun et al. (31) 2014 96 ed 68.8 67.6 dynamic curvilinear 7.3 cap+a hoffman et al. (32) 2014 101 ed 58 nr dynamic/static linear 10 dv+cap saglam et al. (33) 2013 69 ed nr nr static linear 7.2 cap hosseini et al. (34) 2013 57 ed 59 60 static curvilinear 21 dv+a+o chou et al. (a) (35) 2013 89 ed 69.9 69 dynamic curvilinear 7.6 cap+a adi et al. (36) 2013 107 ed nr nr static linear 5.6 cap noh et al. (37) 2012 19 ed nr nr dynamic linear 15.7 cap mulsu et al. (38) 2011 150 or 40.5 50.7 dynamic linear 50 cap+a chou et al. (b) (39) 2011 83 ed 67.6 54.5 static curvilinear 15.7 cap chou et al. (c) (39) 2011 29 ed nr nr static curvilinear 10.3 cap park et al. (40) 2009 30 ed 59.6 56.7 dynamic linear 10 cap+a werner et al. (41) 2007 66 or 38.9 21.2 dynamic linear 57.6 dv+cap milling et al. (42) 2007 40 or 52.5 17.5 dynamic curvilinear 12.5 cap+a or: operation room; icu: intensive care unit; ed: emergency department; nr: not reported; cap: capnography; a: auscultation; dv: direct visualization; fb: fiberoptic bronchoscopy. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 8 table 2: quality assessment of the included studies using quadas-2 tool study risk of bias applicability concerns patient selection index test reference standard flow & timing patient selection index test reference standard chowdhury et al. © © © © © © © chen et al. © © © © © © © men et al. © © © © © © © patil et al. © © © © © © © afzalimoghadam et al. © © © © © © © zamani et al. © © © © © © © kad et al. © © © © © © © kabil et al. © © © © © © © inangil et al. © © © © © © © arya et al. © © © © © © © arafa et al. © © © © © © © zamani et al. ? © © © © © © yang et al. © © © © © © © thomas et al. © ? © © © © © rahmani et al. © © © © © © © masoumi et al. ? © © © © © © lahham et al. ? © © © © © © abhishek et al. ? © © © © © © khosla et al. © © © © © © © karacabey et al. (a) © © © © © © © karacabey et al. (b) © © © © © © © abbasia et al. § © © © © © © sun et al. © © © ? © © © hoffman et al. ? © © © © © © saglam et al. § © © © © © © hosseini et al. © © © © © © © chou et al. (a) ? © © © © © © adi et al. ? © © © © © © noh et al. ? © © ? © © © mulsu et al. © © © © © © © chou et al. (b) ? © © © © © © chou et al. (c) ? © © © © © © park et al. ? © © © © © © werner et al. ? © © © © © © milling et al. ? © © © © © © ©: low risk; §: high risk; ?: unclear risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e68 figure 1: prisma flowchart of the literature search and selection of studies that reported accuracy of ultrasonography for confirmation of endotracheal placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 10 figure 2: forest plot of prevalence of esophageal intubation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e68 figure 3: publication bias of the included studies for analysis of the rate of esophageal intubation confirmed using ultrasonography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 12 figure 4: forest plot of the overall sensitivity of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e68 figure 5: forest plot of the overall specificity of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 14 figure 6: forest plot of the overall positive likelihood ratio of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2021; 9(1): e68 figure 7: forest plot of the overall negative likelihood ratio of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. farrokhi et al. 16 figure 8: forest plot of the overall diagnostic odds ratio (or) of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2021; 9(1): e68 figure 9: hierarchical summary receiver-operating characteristic curve (hsroc) indicating accuracy of ultrasonography for confirmation of endotracheal tube placement. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e63 or i g i n a l re s e a rc h lactate dehydrogenase to albumin ratio as a predictive factor of covid-19 patients’ outcome; a cross-sectional study nafiseh alizadeh1, fatemeh-sadat tabatabaei2, amirali azimi3∗, neda faraji4 †, samaneh akbarpour5, mehrnoush dianatkhah6, azadeh moghaddas7 1. department of pharmaceutical care, baharlou hospital, tehran university of medical sciences, tehran, iran. 2. school of medicine, tehran university of medical sciences, tehran, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 4. department of internal medicine, baharlou hospital, tehran university of medical sciences, tehran, iran. 5. occupational sleep research center, baharlou hospital, tehran university of medical sciences, tehran, iran. 6. department of clinical pharmacy, isfahan university of medical sciences, isfahan, iran. 7. department of clinical pharmacy and pharmacy practice, school of pharmacy and pharmaceutical sciences, cancer prevention research center, seyyed al-shohada hospital, isfahan university of medical sciences, isfahan, iran. received: june 2022; accepted: july 2022; published online: 15 august 2022 abstract: introduction: despite the increasing vaccination coverage, covid-19 is still a concern. with the limited health care capacity, early risk stratification is crucial to identify patients who should be prioritized for optimal management. the present study investigates whether on-admission lactate dehydrogenase to albumin ratio (lar) can be used to predict covid-19 outcomes. methods: this retrospective cross-sectional study evaluated hospitalized covid-19 patients in an academic referral center in iran from may 2020 to october 2020. the area under the receiver operating characteristic (roc) curve (auc) was used to evaluate the value of lar in the prediction of mortality. the yuden index was used to find the optimal cut-off of lar to distinguish severity. patients were classified into three groups (lar tertiles), first: lar<101.46, second: 101.46≤lar< 148.78, and third group: lar≥148.78. logistic regression analysis was used to identify the association between tertiles of lar, as well as the relationship between each one-unit increase in lar with mortality and icu admission in three models, based on potential confounding variables. results: a total of 477 patients were included. among all patients, 100 patients (21%) died, and 121 patients (25.4%) were admitted to intensive care unit (icu). in the third group, the risk of mortality and icu admission increased 7.78 times (or=7.78, ci: 3.95-15.26; p <0.0001) and 4.49 times (or=4.49, ci: 2.01-9.04; p <0.0001), respectively, compared to the first group. the auc of lar for prediction of mortality was 0.768 (95% ci 0.690.81). lar ≥ 136, with the sensitivity and specificity of 72% (95%ci: 62.1-80.5) and 70% (95%ci: 64.9-74.4), respectively, was the optimal cut-off value for predicting mortality. conclusion: high lar was associated with higher odds of covid-19 mortality, icu admission, and length of hospitalization. on-admission lar levels might help health care workers identify critical patients early on. keywords: serum albumin; l-lactate dehydrogenase; covid-19; prognosis; emergency service, hospital cite this article as: alizadeh n, tabatabaei f-s, azimi a, faraji n, akbarpour s, dianatkhah m, moghaddas a. lactate dehydrogenase to albumin ratio as a predictive factor of covid-19 patients’ outcome; a cross-sectional study. arch acad emerg med. 2022; 10(1): e63. https://doi.org/10.22037/aaem.v10i1.1646. ∗corresponding author: amirali azimi; men’s health and reproductive health research center, shohada tajrish hospital, tehran, iran. email: azimi.amirali96@gmail.com aa-azimi@alumnus.tums.ac.ir, tel: (+98) 910 140 7012, orcid: https://orcid.org/0000-0001-7801-7855. † corresponding author: neda faraji; department of internal medicine, baharlou hospital, tehran university of medical sciences, tehran, iran. email: nedafaraji1368@gmail.com, tel: (+98) 919 268 6990, orcid: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. alizadeh et al. 2 1. introduction the most recent global pandemic, coronavirus disease 2019 (covid-19), is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). based on the recent worldwide analysis of covid-19, more than 5 million attributable deaths were reported till november 2021 (1). the symptoms of covid-19 vary in a wide range, from a mild illness to a life-threatening condition. the disease can even be asymptomatic, while the most common clinical symptoms are cough, fever, myalgia, and gastrointestinal symptoms (2, 3). covid-19 can also cause severe organ failures such as acute cardiac injury, acute kidney injury, acute liver injury, and the most known among all, acute respiratory distress syndrome (ards). these conditions can lead the patients to a critical state, which requires intensive care unit (icu) admission and also, in some cases, can cause death (4, 5). outcomes of covid-19 patients mainly depend on the severity of the disease. most individuals with a mild illness had good prognosis (6, 7), while the mortality among critically ill patients was very high (8). according to published data on covid-19, the mortality rate among severely infected individuals was up to 49% (9). generally, in septic patients with acute respiratory failure and multiple organ failure, the mortality may increase up to 35-46% and 60-98%, respectively (10-12). there have been numerous studies investigating factors allowing the prediction of covid-19 severity. some demographic characteristics, a wide range of comorbidities, and many laboratory biomarkers were related to the severity and mortality of covid-19 (13-16). as a negative acute-phase protein, albumin promotes the formation of anti-inflammatory substances, so it plays an essential role in the prognosis of patients with inflammatory events and inhibition of disease progression (17, 18). some previous studies have demonstrated that in non-surviving patients with sepsis, albumin levels are lower (19). since blood lactate dehydrogenase (ldh) level can be determined rapidly as a marker of tissue hypoperfusion, it is widely used in the early risk classification of critical patients admitted to the emergency department (20). similarly, several studies have shown that reduced serum albumin (alb) levels and increased lactate dehydrogenase are associated with covid-19 severity (21-23). scientists have believed that lactate dehydrogenase to albumin ratio integrates multiorgan failure, chronic disease, inflammatory, and nutritional https://orcid.org/0000-0002-9599-4575. factors, which may provide more valuable information than the predictive value of either lactate dehydrogenase or albumin alone (24); however, this has not been sufficiently investigated. despite the increasing vaccination coverage worldwide, covid-19 is still a concern, especially in developing countries. therefore, early risk stratification is crucial for identifying critical patients who should be prioritized for optimal management and allocating the limited human and technical resources to the suitable patients (25). the present study aims to investigate whether on-admission lactate dehydrogenase to albumin ratio (lar) levels can be used as a reliable predictor for clinical outcomes in patients with covid-19. 2. methods 2.1. study design and patients this retrospective cross-sectional study, was conducted on hospitalized patients with clinical manifestations of covid19 and a positive covid-19 polymerase chain reaction (pcr) test or chest computed tomography scan (ct-scan) findings consistent with covid-19, from 1st may 2020 to 31st october 2020, in the baharloo hospital affiliated with tehran university of medical sciences, tehran, iran. the current study was performed under the tenets of the declaration of helsinki. all patients were anonymized during the data collection process, and due to the study’s retrospective nature, informed consent was waived. ethical feasibility was obtained from the ethics committee of tehran university of medical sciences, number ir.tums.vcr.rec.1399.148. 2.2. participants patients under 18 years old, with history of the previous covid-19, and missing data of ldh or alb in the first 48 hours of hospital admission were excluded. since the data bank was used, the sample size was not calculated. none of the patients had been vaccinated against covid-19, as the data gathered for this study belong to the period when vaccination had not started in iran. 2.3. data collection demographic information (age, sex), comorbidities, initial presentations, type of treatment, laboratory data in the first 48 hours of admission, and outcomes were collected from the medical records. only the first test value was included if there were multiple laboratory test values. the co-existing diseases were hypertension (htn), diabetes mellitus (dm), coronary heart disease (chd), previous stroke, chronic obstructive pulmonary disease (copd), chronic kidney disease (ckd), cancer, rheumatoid disease, and hypo/hyperthyroidism. patients were asked if they had ever been informed of having a diagnosis of any mentioned this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e63 comorbidities. the patients were asked if they had experienced fever, chills, myalgia, anorexia, nausea, vomiting, and diarrhea. accurate temperature measurement was also done within the first 24 hours of hospital admission to determine if fever was present. laboratory results included white blood cell (wbc) count, neutrophil count, lymphocyte count, neutrophil to lymphocyte ratio (nlr), hemoglobin (hb), platelets count (ptl), c-reactive-protein (crp), erythrocyte sedimentation rate (esr), blood sugar (bs), blood urea nitrogen (bun), albumin (alb), creatinine (cr), and lactate dehydrogenase (ldh). the clinical chemistry laboratories at the hospital evaluated the blood samples with standard procedures. venous blood samples were collected in tubes, including ethylenediamine tetra-acetic acid. serum ldh level was measured using the hitachi 911 automatic chemistry analyzer (roche). the ldh concentration was presented as units per liter (u/l). blood samples were centrifuged at 3000 rpm for 10 min at room temperature. serum alb level was measured using bromocresol green method and latex coagulating nephelometric assay. given that the half-life of albumin is about 25 days, alb level was included in the study if measured in the first 48 hours of hospital admission. other biochemical markers were measured using standard methods. all patients received nursing, nutritional, and respiratory support. some patients received non-invasive ventilation (niv ), such as nasal oxygen, while some icu-admitted patients received invasive ventilation. hydration, fever management, and pain control were considered. in addition, conservative therapy was performed in patients with gastrointestinal symptoms such as nausea, vomiting, and diarrhea. treatment of patients varied according to their clinical conditions. patients received medications, including nsaids, iv corticosteroids, oral antiviral drugs, and iv antibiotics, according to the covid-19 diagnosis and treatment protocol designed by the iran ministry of health. a chest computed tomography (ct) scan was also done for all patients. bilateral and peripheral ground-glass opacity (ggo), consolidation, reticular pattern, and air bronchogram on chest ct-scan were assumed to be covid-19 in patients with negative pcr test who had the typical clinical manifestation of covid-19 (26, 27). the lactate dehydrogenase to albumin ratio was named lar. patients were classified into three groups based on lar levels (lar tertiles). the first group with lar<101.46 (including 158 patients), the second group with 101.46 ≤ lar < 148.78 (including 159 patients), and the third group with lar≥148.78 (including 160 patients). all the information collection forms were checked for missing data by two researchers, independently. less than 5% of the total data was missing. since this amount does not significantly affect results, it was ignored. 2.4. outcomes outcomes included the length of hospitalization, intensive care unit (icu) admission, and mortality. 2.5. statistical analysis quantitative variables were expressed as mean ± standard deviation (sd) (quantitative variables with normal distribution) or median and interquartile range (iqr) (quantitative variables with non-normal distribution), and categorical variables were presented as frequency and percentage (number (%)). the chi-square (x2), one-way anova, and the kruskal–wallis test statistic were used to compare categorical, quantitative, and skewed variables according to tertiles of lar. logistic regression analysis was used to identify the association between tertiles of lar, as well as the relationship between each one-unit increase in lar with mortality and icu admission in three models, based on potential confounding variables, which were significantly different between tertiles of lar. model one adjusted for age, based on model one, model two added sex, and model three further adjusted for ckd, hyper/hypothyroid, iv corticosteroids, oral antiviral therapy, iv antibiotics, wbc, nlr, crp, esr, bs, o2, bun, and cr. the first tertile of lar was considered a reference point. follow-up duration was defined as the period between hospital admission and mortality, icu admission, or discharge. kaplan-meyer survival analysis was used to calculate the probability of survival in each class of lar. since some data on the time of mortality and icu admission was missing (in about 80 patients), the logistic regression was used instead of cox proportional hazard regression analysis. cox regression analysis was then repeated in a small sample of the population with complete data, and no changes in results were observed. the receiver operating characteristic (roc) curve, and the area under the curve (auc) were used to evaluate the value of lar in prediction of mortality. the yuden index was used to find the optimal cut-off of lar to distinguish severity. all data were analyzed using stata 16 software. the significance threshold was considered less than 0.05 (p-value < 0.05). 3. results 3.1. baseline characteristics of studied cases a total of 477 patients with covid-19 were eventually found eligible to enter the analysis. patients were classified into three groups based on lar levels (lar tertiles). the first group with lar<101.46 (including 158 patients), the second group with 101.46≤lar< 148.78 (including 159 patients), and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. alizadeh et al. 4 table 1: comparing the demographics, initial symptoms, comorbidities, types of treatment, lab data, and outcome between patients with lactate dehydrogenase to albumin ratio (lar) < 101.46 (group 1), 101.46 ≤ lar < 148.78 (group 2), and lar ≥ 148.78 (group 3) variables total (n=477) group1 (n=158) group 2 (n=159) group 3 (n=160) p demographics age (years) 58.56(17.52) 56.21(18.67) 57.45(16.8) 61.98(16.61) 0.008 male sex 263 (55.1) 78 (49.4) 84 (52.8) 101 (63.1) 0.037 initial symptoms cough 314 (65.8) 106 (67.1) 112 (70.4) 96 (60) 0.133 fever 248 (52) 77 (48.7) 82 (51.6) 89 (55.6) 0.466 myalgia 160 (33.5) 54 (34.2) 56 (35.2) 50 (31.3) 0.738 chills 142 (29.8) 44 (27.8) 50 (31.4) 48 (30) 0.780 nausea 80 (16.8) 35 (22.2) 22 (13.8) 23 (14.4) 0.086 anorexia 66 (13.8) 16 (10.1) 22 (13.8) 28 (17.8) 0.163 vomiting 36 (7.5) 12 (7.6) 10 (6.3) 14 (8.8) 0.707 diarrhea 30 (6.3) 12 (7.6) 10 (6.3) 8 (5) 0.635 comorbidity hypertension 166 (34.8) 50 (31.6) 50 (31.4) 66 (41.3) 0.110 diabetes mellitus 146 (30.6) 43 (27.2) 45 (28.3) 58 (36.3) 0.161 chronic heart disease 86 (18) 25 (15.8) 27 (17) 34 (21.3) 0.414 history of stroke 42 (8.8) 13 (8.2) 11 (6.9) 18 (11.3) 0.375 hyper/hypothyroidism 18 (3.8) 3 (1.9) 5 (3.1) 4 (2.5) 0.037 copd 13 (2.7) 6 (3.8) 4 (2.5) 3 (1.9) 0.563 chronic kidney disease 12 (2.5) 1 (0.6) 2 (1.3) 9 (5.6) 0.008 rheumatoid disease 9 (1.9) 1 (0.6) 5 (3.1) 3 (1.9) 0.259 cancer 3 (0.6) 0 0 3 (1.9) 0.050 treatments nsaids 302 (63.3) 102 (64.6) 105 (66) 95 (59.4) 0.431 iv antibiotics 228 (47.8) 57 (36.1) 72 (45.3) 99 (61.9) <0.0001 oral antiviral 171 (35.8) 32 (20.3) 57 (35.8) 82 (51.3) <0.0001 iv corticosteroids 109 (22.9) 20 (12.7) 32 (20.1) 57 (35.6) <0.0001 laboratory data wbc (109 /l) 7.54 ±5.57 7.22±3.69 6.36 ± 3.41 9.04 ± 8.00 <0.0001 neutrophil (percentage) 74.39± 11.36 70.01 ± 10.25 73.77± 10.74 79.33± 11.14 <0.0001 lymphocyte (percentage) 20.27± 10.69 24.47± 10.01 20.94± 10.80 15.45± 9.25 <0.0001 nlr 5.61± 5.15 4.03± 3.73 4.91± 4.05 7.86± 6.43 <0.0001 hemoglobin (g/dl) 13.42± 10.35 13.11 ± 1.78 14.57± 17.71 12.59± 1.91 0.210 platelet count (109 /l) 211.90±92.57 218.21±96.47 200.34± 84.91 217.16± 95.39 0.155 crp (mg/l) 47.82± 48.82 22.97± 25.07 54.64± 70.24 65.60± 25.20 <0.0001 esr (mm/hour) 56.68± 29.78 43.34± 25.54 58.61± 29.13 67.94± 29.31 <0.0001 blood sugar (mg/dl) 151.44±80.57 138.24± 61.24 160.51±91.91 155.47±84.05 0.036 oxygen saturation (%) 90.38±7.21 91.86± 5.83 91.48± 4.89 87.82± 9.37 <0.0001 bun (mg/dl) 44.63± 29.01 36.55± 19.98 41.10± 21.61 56.11± 38.09 <0.0001 serum creatinine (mg/dl) 1.26±0.68 1.10 ± 0.35 1.19± 0.62 1.48± 0.89 <0.0001 ldh (unit/l) 583.07±283.61 371.33± 62.85 515.33± 74.37 859.47±324.64 <0.0001 albumin (g/dl) 4.22±0.56 4.60±0.36 4.27±0.46 3.80±0.56 <0.0001 outcome mortality 100 (21) 13 (8.2) 19 (11.9) 68 (42.5) <0.0001 icu admission 121 (25.4) 15 (9.5) 28 (17.6) 78 (48.8) <0.0001 hospital stay (day) 6 (6) 6 (5) 6 (6) 8 (10) <0.0001 all data are reported as frequency (%), except for age and laboratory results, which are reported as mean ± standard deviation, and hospital stay, which is reported as median (iqr). copd: chronic obstructive pulmonary disease; nsaids: non-steroidal anti-inflammatory drugs; iv: intravenous; wbc: white blood cell count; crp: c-reactive protein; esr: erythrocyte sedimentation rate; bun: blood urea nitrogen; ldh: lactate dehydrogenase; nlr: neutrophil to lymphocyte ratio; icu: intensive care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e63 figure 1: trend of mortality and intensive care unit (icu) admission based on quantiles of lactate dehydrogenase to albumin ratio (lar); p < 0.0001 for trend of mortality and p <0.0001 for trend of icu admission. figure 2: a: kaplan-meier survival analysis of covid-19 cases based on lactate dehydrogenase to albumin ratio (lar); b: predicting mortality of covid-19 cases using receiver operating characteristic (roc) curve analysis for lar in 136 cut-off point. the third group with lar≥148.78 (including 160 patients). the mean age of patients was 58.56 (range: 41 – 76) years. two hundred and sixty-three patients (55.1%) were male. age and sex distribution were significantly different between groups with different lars (p = 0.008 and p = 0.037, respectively). the demographic characteristics, initial symptoms, comorbidities, types of treatment, and laboratory data are shown in table 1. the initial symptoms among all patients were as follows: cough in 314 patients (65.8%), fever in 248 patients (52%), and the other symptoms had a lower prevalence. the groups were similar in terms of initial symptoms (p > 0.05). hypertension (34.8%) and diabetes mellitus (30.6%) were the most common comorbidities. coexisting comorbidities, including hyper/hypothyroidism and ckd, were significantly different between groups with different lars (p = 0.037 and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. alizadeh et al. 6 table 2: multivariable logistic regression analysis for independent predictive factors of mortality and intensive care unit (icu) admission among covid-19 cases after adjustment for potential confounding variables variables group 1 (n=158) group 2 (n=159) group 3 (n=160) p* 1 unit change# mortality age 1 1.05 (0.44-2.51) 3.73 (1.65-8.62) <0.0001 1.02 (1.01-1.03) age and sex 1 1.52 (1.05-3.26) 7.90 (4.04-15.43) <0.0001 1.02 (1.01-1.03) multivariate 1 1.53 (0.73-3.25) 7.78 (3.95-15.26) <0.0001 1.01 (1.00-1.02) icu admission age 1 2.04 (1.03-4.02) 8.54 (4.57-15.95) <0.0001 1.01 (1.00-1.01) age and sex 1 2.03 (1.03-4.02) 8.47 (4.52-15.88) <0.0001 1.01 (1.00-1.02) multivariate 1 1.45(0.65-2.21) 4.49 (2.01-9.04) <0.0001 1.02 (1.01-1.03) *: p value for trend. #: 1-unit increase in lar. all measures are presented as adjusted odds ratio with 95% confidence interval. group 1: lar < 101.46, group 2: 101.46 ≤ lar < 148.78, and group 3: lar ≥ 148.78. lar: lactate dehydrogenase to albumin ratio. p = 0.008, respectively). the treatment of patients varied according to the patients’ clinical condition. use of iv corticosteroids, oral antiviral therapy, and iv antibiotics were significantly different between groups with different lars (p <0.0001). wbc, neutrophil count, nlr, crp, esr, bs, bun, cr, and ldh were significantly increased among all laboratory results. in contrast, lymphocyte count, blood oxygen saturation, and alb were significantly decreased in groups with higher lar (p <0.0001). 3.2. outcomes the outcomes of the population study are shown in table 1. among all patients, 100 patients (21%) died, 121 patients (25.4%) were admitted to icu, and 256 patients (53.6%) were discharged. the median length of hospitalization was six days. the mortality rate, icu admission, and length of hospitalization were significantly different between groups with different lars (p <0.0001). after adjustment for ckd, hyper/hypothyroid, iv corticosteroids, oral antiviral therapy, iv antibiotics, wbc, nlr, crp, esr, bs, o2, bun, and cr (based on potential confounding variables, which were significantly different between tertiles of lar), in the third group, the risk of mortality increases 7.78 times (or=7.78, ci (3.95-15.26)) compared to the first group (p-value for trend < 0.0001). besides, the risk of icu admission among the patients with lar ≥ 148.78 was 4.49 times (or=4.49, ci (2.01-9.04)) compared to those with lar<101.46 (p-value for trend < 0.0001). the results suggested that each one-unit increase in lar increases the risk of mortality and icu admission 1.01 times (1.00-1.02) and 1.02 times (1.02-1.03), respectively (table 2). the repetition of this analysis in the more-stratified lar levels (quantiles of lar) indicated significantly higher mortality (p-value for trend< 0.0001) and icu admission (p-value for trend < 0.0001) with increase in lar. the trends of mortality and icu admission based on quantiles of lar are shown in figure 1. the probability of survival based on tertiles of lar was estimated using kaplan meier method. as shown in figure 2, the probability of survival increases with decrease in lar, especially in the first fourteen days of hospital admission. lar was taken as a candidate for roc analysis (figure 3). the auc of lar was 0.7684 (95% ci 0.690.81), which indicates that lar can be an accurate predictor of mortality (p < 0.0001). using the yuden index, lar ≥ 136, with the sensitivity and specificity of 72% (95%ci: 62.1-80.5) and 70% (95%ci: 64.9-74.4), respectively, was the optimal cut-off value in predicting mortality (positive predictive value 38.7 (95%ci: 31.746.1), negative predictive value 90.4 (95% ci: 86.4-93.5)). 4. discussion in the present study, the mortality rate, icu admission, and length of hospitalization were significantly increased in patients with higher lar. lar ≥ 136, with the sensitivity and specificity of 72% and 70%, respectively, was the optimal predictive threshold for covid-19 mortality. with the limited health care capacity, numerous studies have investigated factors allowing the prediction of covid19 severity and mortality in the early stages. the prognostic role of elevated crp, esr, bun, and cr has been highlighted in several investigations of covid-19 progression (13, 14, 21, 22). besides, previous studies indicated that older age, one or more coexisting comorbidities, high wbc, elevated neutrophil count, elevated ldh, lower lymphocyte count, and low serum alb levels are associated with adverse outcomes in patients with covid-19 (28-30). the present study’s findings showed that in patients with higher lar, lymphocyte count and serum albumin levels were significantly decreased. in contrast, age, coexisting chronic kidney disease and hyper/hypothyroidism, white blood cell count, neutrophil count, nlr, crp, esr, bs, bun, creatinine, and ldh were significantly increased. besides, in the current this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e63 study population, the probability of survival decreased with increase in lar. in patients with lar≥148.78, the risk of mortality and icu admission increased 7.78 and 4.49 times, respectively, compared to those with lar<101.46. ldh and albumin are routinely tested and readily available markers in many clinical practices. since different mechanisms regulate these two biomarkers, lar can reduce the impact of a single factor on the regulation mechanism (24). several studies have examined the prognostic role of lar in many respiratory and infectious diseases. lar was independently associated with in-hospital death in a korean population of patients with severe infections requiring intensive care (31). similarly, the prognostic role of lar in patients with lower respiratory tract infection (lrti) who were admitted to an emergency department was explored by lee bk et al.; lar was considered an independent prognostic factor for in-hospital mortality in patients with lrti (32). the predictive value of lar, particularly in patients with covid19, has not been sufficiently investigated. in a recent study conducted in china on 321 covid-19 patients, lar was significantly associated with in-hospital death and had a high specificity and sensitivity in differentiating critical patients from mild ones (24). in conclusion, to the best of our knowledge, the current study is one of the first investigations to describe a cut-off value for lar as an influential predictor of covid-19 severity and mortality. these findings will help healthcare workers identify high-risk patients who should be prioritized and improve covid-19 survival. 4.1. limitation this study has certain limitations that have to be taken into consideration. first, since this study was retrospective in nature, it thus has innate limitations regarding selection bias. second, not all laboratory biomarkers with the potential for prognosis have been obtained (such as d-dimer and ferritin). third, we only included patients for whom ldh and albumin were measured. forth, all laboratory data were obtained in the first 48 hours of hospital admission; thus, a single measurement may have limited prognostic value, and additional measurements may provide more reliable information. fifth, the data was collected from a single center, limiting these results’ generalizability. in the future, further investigations with large populations, multiple centers, and continuous monitoring are required to describe the prognostic role, diagnostic sensitivity, specificity, and positive and negative predictive values of lar with more precision. 5. conclusion the mortality rate, icu admission, and length of hospitalization were significantly increased in patients with higher lar. lar ≥ 136, with the sensitivity and specificity of 72% and 70%, was the optimal predictive threshold for covid-19 mortality. 6. declarations 6.1. acknowledgments none. 6.2. authors’ contributions conceptualization: md. data curation: na. formal analysis: sa. funding acquisition: none. methodology: sa, na, nf. visualization: ft, nf, na, aa. writing—original draft: ft, aa. writing—review, and editing: ft, aa, am. all authors read and approved the final draft. 6.3. funding and supports none. 6.4. conflict of interest the authors have no conflicts of interest to declare for this study. 6.5. data availability data of the study are available and will be provided if anyone needs them. references 1. coronavirus w. dashboard| who coronavirus (covid19) dashboard with vaccination data. 2021. 2. team e. the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid19)—china, 2020. china cdc wkly. 2020;2(8):113. 3. pan f, ye t, 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oh s-k, park j-s, you y-h, jeong w-j, et al. lactate dehydrogenase to albumin ratio as a prognostic factor for patients with severe infection requiring intensive care. medicine (baltimore). 2021; 100(41): e27538. 32. lee b-k, ryu s, oh s-k, ahn h-j, jeon s-y, jeong w-j, et al. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e63 lactate dehydrogenase to albumin ratio as a prognostic factor in lower respiratory tract infection patients. am j emerg med. 2022;52:54-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e58 or i g i n a l re s e a rc h predictive factors of 30-day adverse events in acute heart failure after discharge from emergency department; a historical cohort study siriwimon tantarattanapong1∗, keerati keeratipongpun1 1. department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla, thailand. received: june 2021; accepted: july 2021; published online: 1 september 2021 abstract: introduction: the rates of unscheduled emergency department (ed) visits and readmissions after discharge from the ed in acute heart failure (ahf) patients are high. this study aimed to identify the predictive factors of 30-day adverse events after discharge from the ed. methods: a retrospective study was conducted from 2017 to 2019 in patients diagnosed with ahf and discharged from the ed at a tertiary university hospital. thirty-day adverse events were defined as (i) unscheduled revisit to the ed with ahf, (ii) hospital admission from ahf, and, (iii) death after discharge from the ed. the predictive factors of 30-day adverse events were examined using multivariate analyses by logistic regression. results: 421 patients with the median age of 73 (iqr: 63-81) years were studied (52.3% male). 81 (19.2%) patients had 30-day adverse events. significant predictive factors of 30-day adverse events consisted of underlying valvular heart disease (or = 2.46; 95%ci: 1.27-4.78; p = 0.008), chronic obstructive pulmonary disease (copd) (or = 0.08; 95%ci: 0.01-0.64; p=0.001), malignancy (or=3.63; 95%ci: 1.17-11.24; p = 0.031), new york heart association functional class iii (or = 4.88; 95%ci: 0.93-25.59) and iv (or = 7.23; 95% ci: 1.37-38.08) at the ed (p = 0.035), and serum sodium <135 mmol/l (or = 2.20; 95%ci: 1.174.14; p = 0.014). precipitating factors were anemia (or = 2.42; 95%ci: 1.16-5.02; p = 0.021), progressive valvular heart disease (or = 3.52; 95%ci: 1.35-7.85; p = 0.009), acute kidney injury (or = 6.98; 95%ci: 2.32-20.96; p < 0.001), time to diuretic administration >60 minutes after ed arrival (or = 3.89; 95%ci: 2.16-7.00; p < 0.001), and no discharge advice for follow-up (or = 2.30; 95%ci: 1.10-4.77; p = 0.028). conclusion: ahf patients who had good response to intravenous diuretics and were discharged from the ed were at high risk for 30-day adverse events. ten factors predicted 30-day adverse events after discharge from the ed. keywords: heart failure; patient discharge; emergency service; hospital; patient readmission; patient admission cite this article as: tantarattanapong s, keeratipongpun k. predictive factors of 30-day adverse events in acute heart failure after discharge from emergency department; a historical cohort study. arch acad emerg med. 2021; 9(1): e58. https://doi.org/10.22037/aaem.v9i1.1271. 1. introduction acute heart failure (ahf) is defined as a rapid onset of clinical syndromes of heart failure such as dyspnea, fatigue, pulmonary congestion, and peripheral edema, which can be new onset (de novo) or due to the worsening of preexisting heart failure (1). the incidence of ahf is approximately 1 million cases per year in the united states of america (2). the patients present to emergency departments (eds) and emer∗corresponding author: siriwimon tantarattanapong; department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla, 90110, thailand. phone: (66)74451705, fax: (66)74-451704, email: tsiriwimon.er@gmail.com, orcids: https://orcid.org/0000-0002-4792-373x. gency physicians (ep) evaluate, diagnose, and treat ahf patients. the decision making for disposition is crucial and a challenging issue for the ep. if the ep makes a decision that results in an inappropriate disposition, the risks of morbidity and mortality will increase (3, 4). about 16% to 36% of ahf patients can be discharged from the ed after a brief period of observation (3-6). the rate of unscheduled ed visits was reported to be 26% and readmission rate was 15% in 30 days (4). the 7-day and 30-day mortality rates in ahf patients after discharge from the ed were reported to be 2% and 3.3%, respectively (3, 5). from a previous study, the factors that influenced an unscheduled ed visit and readmission of ahf patients after discharge from the ed included underlying ischemic heart disease, pulmonary disease, valvular heart disease, anemia, malignancy, glomerular filtration this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and k. keeratipongpun 2 rate (gfr) <60 ml/min/1.73 m2, and no administration of an intravenous diuretic agent (4-6). the factors that predicted ahf mortality were underlying ischemic heart disease, pulmonary disease, valvular heart disease, malignancy, and elevated potassium and troponin-t levels, whereas consumption of angiotensin-converting enzyme inhibitor, angiotensin ii receptor blocker, beta-blocker, and spironolactone were associated with lower mortality rates (4-6). consideration for discharge from the ed depends on the clinical condition, good response to initial therapy, and no de novo ahf (7). however, the risk factors that influence an unscheduled ed visit, readmission, or mortality are not considered in the discharge criteria. the aim of this study was to identify the predictive factors of 30-day adverse events in ahf patients after discharge from the ed to help the eps make appropriate dispositions. 2. methods 2.1. study design and setting a retrospective cohort study was conducted at the ed of songklanagarind hospital, which is a tertiary university hospital in southern thailand. the data were collected from february 2017 to june 2019. ethics approval was obtained from the institutional ethics committee board of the faculty of medicine at prince of songkla university (ethics code: rec.62-167-20-4). 2.2. participants the inclusion criteria were patients aged ≥15 years, diagnosed with ahf, and discharged home from the ed based on the decision of the ep and internists. patients admitted or referred to other hospitals were not included in this study. the exclusion criteria were (i) end-stage renal disease with hemodialysis or peritoneal dialysis, (ii) pregnancy, (iii) incomplete discharge criteria, and (iv) lost to follow-up. 2.3. procedure when the patients presented to the ed, the ep evaluated the history, performed physical examination, and carried out investigations to diagnose ahf according to the framingham criteria and echocardiography. the framingham criteria consist of (i) acute pulmonary edema, (ii) cardiomegaly, (iii) hepatojugular reflex, (iv) neck vein distension, (v) paroxysmal nocturnal dyspnea or orthopnea, (vi) rales, and (vii) third heart sound gallop. the minor criteria consist of (i) ankle edema, (ii) dyspnea on exertion, (iii) hepatomegaly, (iv) nocturnal cough, (v) pleural effusion, and (vi) tachycardia (>120 beats/minute). ahf was diagnosed when two major criteria or one major and two minor criteria were met (8). after the patients were diagnosed, the ep looked for and worked up the precipitating causes and management of ahf using intravenous diuretics. the response was observed to fulfill the discharge criteria. criteria for discharge consisted of (i) patient-reported subjective improvement, (ii) resting heart rate <100 bpm, (iii) no hypotension, (iv) adequate urine output, (v) oxygen saturation >95% in room air, and (vi) no de novo heart failure (7). adequate urine output was defined as urine output >100 ml/h after intravenous diuretic administration (9). 2.4. data gathering the data collected from the medical records included patient baseline characteristics, history taking, physical examination, precipitating factors, diagnosis, investigations, treatments, and 30-day adverse events. thirty-day adverse events were defined as (i) unscheduled revisit to the ed with ahf within 30 days, (ii) hospital admission due to ahf within 30 days after discharge from the ed, and (iii) death within 30 days after discharge from the ed. time to diuretic administration was considered as the interval from the time the patient entered the ed until the patient received the first dose of an intravenous diuretic agent. 2.5. outcome measurements the primary outcome was to identify the predictive factors of 30-day adverse events in ahf patients who were discharged home from the ed. the secondary outcome was to identify the incidence of 30-day adverse events. 2.6. statistical analysis the sample size was calculated using the n4studies based on a study by miró et al. (4). the statistical analysis was conducted using r software version 3.6.1. continuous variables were analyzed and are reported as median and interquartile range (iqr), while discrete variables are reported as percentage. all data were based on non-parametric frequency distributions. the univariate model analyzed the baseline characteristics, clinical presentations, investigations, and treatments. the data were compared between subjects with and without 30-day adverse events after discharge from the ed. continuous variables were compared using the mannwhitney u-test. categorical variables were compared using the x2 test or fisher’s exact test as indicated. significant predictive factors associated with 30-day adverse events in ahf (p < 0.2) identified during the univariate analysis were introduced into a logistic regression model with backward stepwise selection. first-order interaction terms with combinations of all independent predictors were introduced into the multivariate model one at a time. generally, interaction terms were considered with statistical significance set at p < 0.05 and no significant interaction between the included variables in the final logistic regression models. modeling results are shown as odds ratio (or) with 95% confidence inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e58 table 1: comparing the baseline characteristics between acute heart failure patients with and without 30-day adverse outcome variables 30-day adverse event p value with (n=81) without (n=340) age (year) median (iqr) 73 (62,79) 73 (62,81) 0.305 sex male 36 (44.4) 184 (54.1) 0.149 female 45 (55.6) 156 (45.9) baseline nyha functional class i 3 (3.7) 37 (10.9) ii 35 (43.2) 132 (38.8) iii 26 (32.1) 89 (26.2) 0.227 iv 2 (2.5) 17 (5.0) no record 15 (18.5) 65 (19.1) comorbidity hypertension 49 (60.5) 230 (67.6) 0.274 diabetes mellitus 32 (39.5) 119 (35.0) 0.528 hyperlipidemia 34 (42.0) 138 (40.6) 0.918 ischemic heart disease 46 (56.8) 184 (54.1) 0.757 valvular heart disease 41 (50.6) 93 (27.4) <0.001 atrial fibrillation 20 (24.7) 71 (20.9) 0.550 chronic kidney disease 29 (35.8) 90 (26.5) 0.124 cerebrovascular disease 12 (14.8) 37 (10.9) 0.424 copd 1 (1.2) 24 (7.1) 0.063 malignancy 9 (11.1) 14 (4.1) 0.025 peripheral arterial disease 2 (2.5) 9 (2.6) 1.000 medication used diuretics 70 (86.4) 272 (80.0) 0.241 acei 11 (13.6) 82 (24.1) 0.057 arb 5 (6.2) 49 (14.4) 0.071 beta-blocker 47 (58.0) 213 (62.6) 0.521 nitrate 20 (24.7) 66 (19.4) 0.365 digoxin 10 (12.3) 32 (9.4) 0.558 data are presented as n (%) or median and interquartile range (iqr). nyha: new york heart association; copd: chronic obstructive pulmonary disease; acei: angiotensin-converting enzyme inhibitors; arb: angiotensin receptor blockers. terval (ci). a two-tailed p < 0.05 was selected as the level of statistical significance. 3. results 3.1. baseline characteristics from a total of 614 ahf patients, 421 met the inclusion criteria of this study. the median age was 73 (iqr 63-81) years (52.3% male). the percentages of patients with underlying valvular heart disease (50.6% vs. 27.4%; p < 0.001) and malignancy (11.1% vs. 4.1%; p = 0.025) were significantly higher in the 30-day adverse event group. none of the medications used by the patients were statistically different between the two groups (table 1). in patients with adverse events, both median systolic and diastolic blood pressures were lower than the no adverse event group (table 2). the mean serum sodium level in the 30day adverse event group was also lower. the statistically significant precipitating factors that led to 30-day adverse events were anemia, non-compliance with dietary restrictions, acute kidney injury, and progressive valvular heart disease. the median times to diuretic administration in the no 30-day adverse event group and 30-day adverse event group were 53 minutes and 70 minutes, respectively (p = 0.040). the median total doses of diuretic agents were higher in the 30-day adverse event group (table 3). 3.2. outcomes the incidence rate of 30-day adverse events after discharge from the ed was 19.2% (81/421). the rates of unscheduled revisit, hospital admission, and mortality within 30 days after discharge from the ed were 17.1%, 7.6%, and 1.0%, respectively (figure 1). based on multivariate analysis, the factors that increased the odds of 30-day adverse events included underlying valvular heart disease, malignancy, new this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and k. keeratipongpun 4 table 2: comparing the clinical presentations and laboratory findings between acute heart failure patients with and without 30-day adverse outcome variables 30-day adverse event p value with (n=81) without (n=340) nyha functional class at the ed i 0 (0) 0 (0) ii 2 (2.5) 31 (9.1) iii 29 (35.8) 138 (40.6) 0.050 iv 36 (44.4) 105 (30.9) no record 14 (17.3) 66 (19.4) initial vital signs sbp (mmhg) 123.0 (110.0,143.0) 138.0(120.0,154.2) <0.001 dbp (mmhg) 70.0 (61.0,79.0) 76.5 (65.0,87.0) 0.001 pr (bpm) 80.0 (70.0,96.0) 82.0 (70.0,96.0) 0.967 rr (breaths/minute) 28.0 (24.0,32.0) 28.0 (24.0,32.0) 0.499 spo2 (%) 97.0 (95.0,99.0) 97.0 (95.0,99.0) 0.648 laboratory findings gfr (ml/min/1.73 m2 ) 48.5 (32.0,67.0) 57.5 (37.2,75.8) 0.097 sodium (mmol/l) 136.1 (133.0,140.8) 138.9 (135.6,141.5) <0.001 potassium (mmol/l) 3.9 (3.5,4.3) 4.0 (3.6,4.3) 0.447 troponin-t (ng/ml) 44.8 (29.8,70.3) 34.6 (19.4,62.4) 0.032 pro-bnp (pg/ml) 8,041.0 (3,349.0-18,394.0) 4,805.0 (2,181.5-9,590.0) 0.110 precipitating factors infection 14 (17.3) 46 (13.5) 0.489 non-steacs 5 (6.2) 10 (2.9) 0.179 anemia 20 (24.7) 48 (14.1) 0.031 poor drug compliance 16 (19.8) 92 (27.1) 0.226 non-compliance with dr 16 (19.8) 115 (33.8) 0.020 arrhythmia 3 (3.7) 15 (4.4) 1.000 hypertension 4 (4.9) 26 (7.6) 0.541 acute kidney injury 10 (12.3) 11 (3.2) 0.002 progressive vhd 19 (23.5) 24 (7.1) <0.001 data are presented as number (%) or median and interquartile range (iqr). nyha: new york heart association; ed: emergency department; sbp: systolic blood pressure; dbp: diastolic blood pressure; pr: pulse rate; rr: respiratory rate; spo2: oxygen saturation; dr: dietary restrictions; vhd: valvular heart disease; gfr: glomerular filtration rate; pro-bnp: n-terminal pro b-type natriuretic peptide; non-steacs: non-st elevation acute coronary syndromes. york heart association (nyha) functional class iii and iv at the ed, and sodium level <135 mmol/l. the precipitating factors were anemia, progressive valvular heart disease, acute kidney injury, door-to-diuretic time >60 minutes, and no advice for follow-up (table 4). however, copd was a predictive factor that decreased 30-day adverse events. 4. discussion the overall incidence of adverse events in ahf patients discharged from the ed was 19.2%, which consisted of unscheduled revisits at the ed within 30 days (17.1%), hospital admission within 30 days (7.6%), and death within 30 days (1.0%). the incidences of admission to the hospital within 30 days and death within 30 days were close to previous studies at 15.7% and 1.7-4.0%, respectively (4, 5). this study revealed the predictive factors associated with 30day adverse events after discharge from the ed, which included underlying valvular heart disease, malignancy, copd, nyha functional class iii and iv at the ed, and serum sodium level. in addition, the precipitating factors were identified to be anemia, progressive valvular heart disease, acute kidney injury, time to diuretic administration, and no advice for follow-up. the predictive factors that increased 30-day adverse events after discharge home from the ed in this study consisted of underlying valvular heart disease (adjusted or [adj. or] = 2.46; 95%ci: 1.27-4.78) (p = 0.008), malignancy (adj. or = 3.63; 95%ci: 1.17-11.24) (p = 0.031), and nyha functional class iii and iv at the ed (adj. or = 4.88; 95%ci: 0.93-25.59 and adj. or = 7.23; 95%ci: 1.37-38.08, respectively) (p = 0.035), which were quite similar to previous studies (4, 6). in this study, copd was a predictive factor that decreased 30day adverse events (adj. or = 0.08; 95%ci: 0.01-0.64) (p = this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e58 table 3: comparing the emergency department management and disposition characteristics between acute heart failure patients with and without 30-day adverse outcome variables 30-day adverse event p value with (n=81) without (n=340) medication time to diuretic (minutes) 70.0 (40.0,100.0) 53 (36.0,90.0) 0.040 initial dose of iv diuretics (mg) 40.0 (40.0,80.0) 40.0 (40.0,80.0) 0.170 total dose of iv diuretics (mg) 120.0 (40.0,240.0) 80.0 (40.0,130.0) 0.010 consult with internist yes 23 (28.4) 75 (22.1) 0.286 discharge instruction items lifestyle modification 22 (27.2) 88 (25.9) 0.925 drug compliance 17 (21.0) 54 (15.9) 0.348 warning signs and symptoms 40 (49.4) 134 (39.4) 0.130 advice for follow-up 61 (75.3) 295 (86.8) 0.017 ed length of stay (hours) median (iqr) 4.9 (3.5,6.1) 4.5 (3.3,5.6) 0.166 data are presented as number (%) or median and interquartile range (iqr). iv: intravenous; ed: emergency department. table 4: predictive factors of 30-day adverse events of patients with acute heart failure who were discharged from the emergency department based on the results of multivariate logistic regression analysis variables crude or adjusted or p value comorbidity valvular heart disease 2.72 (1.66-4.47) 2.46 (1.27-4.78) 0.008 copd 0.16 (0.02-1.23) 0.08 (0.01-0.64) 0.001 malignancy 2.91 (1.21-6.99) 3.63 (1.17-11.24) 0.031 nyha functional class at ed iii 3.26 (0.74-14.38) 4.88 (0.93-25.59) 0.035 iv 5.31 (1.21-23.33) 7.23 (1.37-38.08) precipitating factors anemia 1.99 (1.11-3.60) 2.42 (1.16-5.02) 0.021 progressive valvular heart disease 4.03 (2.08-7.81) 3.52 (1.35-7.85) 0.009 acute kidney injury 4.21 (1.72-10.3) 6.98 (2.32-20.96) <0.001 door-to-diuretic time >60 min 2.67 (1.62-4.4) 3.89 (2.16-7.00) <0.001 sodium <135 mmol/l 2.07 (1.22-3.53) 2.20 (1.17-4.14) 0.014 no advice for follow-up 2.15 (1.19-3.89) 2.30 (1.10-4.77) 0.028 data are presented with 95% confidence interval; or: odds ratio; copd: chronic obstructive pulmonary disease; nyha: new york heart association; ed: emergency department. 0.001), which was contrary to other studies (3, 4). this inconsistency may have resulted due to different prevalence rates of copd between the studies. the prevalence of copd in this study was 5.9%, whereas the prevalence rates of copd in two previous studies were 21.8% and 25.5% (3, 4). the lower prevalence of copd in this study was possibly due to different inclusion criteria. this study included only ahf patients who were discharged directly from the ed, whereas the cited studies included ahf patients discharged from the ed and ahf patients admitted to the hospital. patients admitted to the hospital generally have an underlying disease such as copd. therefore, this study reported fewer patients with copd. lower serum sodium level was an associated factor for increased mortality in ahf patients (10). a serum sodium level <135 mmol/l was a predictive factor of adverse events in this study (adj. or = 2.20; 95%ci: 1.17-4.14) (p = 0.014). the time to diuretic administration influenced hospital mortality rate. a study by matsue et al. and maisel reported that ed arrivals who received an intravenous diuretic agent within 60 minutes in ahf patients had a lower hospital mortality rate (11, 12). the results of this study showed that a door-to-diuretic time >60 minutes predicted 30-day adverse events (adj. or = 3.89; 95%ci: 2.16-7.00) (p < 0.001). therethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and k. keeratipongpun 6 figure 1: study inclusion flow diagram. ed: emergency department. fore, the ep should give early administration of intravenous diuretic agents within 60 minutes in ahf patients to decrease the occurrence of adverse events. significant precipitating factors to predict 30-day adverse events in this study were anemia (adj. or = 2.42; 95%ci: 1.165.02) (p = 0.021), progressive valvular heart disease (adj. or = 3.52; 95%ci: 1.35-7.85) (p = 0.009), and acute kidney injury (adj. or = 6.98; 95%ci: 2.32-20.96) (p < 0.001). the ep should consider these factors in addition to the response to initial treatment prior to discharge. in accordance with the 2015 recommendations of european society of cardiology, the ep should identify low-risk features, absence of any known highrisk features, and a good response to the initial treatment for a safe discharge (7). examples of high-risk features are significantly elevated natriuretic peptide levels, low blood pressure, worsening renal failure, hyponatremia, and positive troponin. in ahf patients who have a good response to initial therapy and are considered for discharge home, the ep must give discharge instructions to present for follow-up within 72 hours (7). a study by vansuch demonstrated that when all discharge instructions were not given, the ahf patients had an increased risk for readmission (13). in this study, no advice for follow-up was a predictive factor of 30-day adverse events this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e58 (adj. or = 2.30; 95%ci: 1.10-4.77) (p = 0.028). ideally the patients should present for follow-up within 72 hours after discharge, but this depends on the hospital context. the patients should follow the instructions and return to the ed. the ep should make the decision for a safe discharge based on good response to initial treatment, low-risk features, and an organized system for follow-up. however, low-risk and high-risk features to predict 30-day adverse events should be researched further in the future. 5. limitations this study was a single-center retrospective study. therefore, missing data on the follow-up of patients affected the mortality rate due to the unknown status of some patients. 6. conclusion it seems that ahf patients who have good response to intravenous diuretics and are discharged from the ed are at high risk for 30-day adverse events. the significant factors to predict an increased risk of 30-day adverse events after discharge from the ed consisted of underlying valvular heart disease, malignancy, nyha functional class iii and iv at the ed, and serum sodium level <135 mmol/l. the precipitating factors were anemia, progressive valvular heart disease, acute kidney injury, time to diuretic administration >60 minutes after ed arrival, and no advice for follow-up as part of discharge instructions. on the other hand, copd was a low risk factor of 30-day adverse events in this study. 7. declarations 7.1. acknowledgments the authors thank kingkarn waiyanak for search and retrieval of articles, glenn k. shingledecker for his help in editing the manuscript, and the faculty of medicine for funding this research. 7.2. funding and supports the faculty of medicine, prince of songkla university funded this research. 7.3. author contribution keerati keeratipongpun and siriwimon tantarattanapong performed the literature research, study design, data collection, data analysis, data interpretation, and writing the manuscript. both authors contributed to data analysis, drafting, and the critical revisions of the paper and agree to be accountable for all aspects of the work. 7.4. conflict of interest the authors declare they have no conflict of interest. references 1. ponikowski p, voors aa, anker sd, bueno h, cleland jgf, coats ajs, et al. 2016 esc guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc)developed with the special contribution of the heart failure association (hfa) of the esc. european heart journal. 2016;37(27):2129-200. 2. collins s, storrow ab, albert nm, butler j, ezekowitz j, felker gm, et al. early management of patients with acute heart failure: state of the art and future directions. a consensus document from the society for academic emergency medicine/heart failure society of america acute heart failure working group. journal of cardiac failure. 2015;21(1):27-43. 3. lee ds, stitt a, austin pc, stukel ta, schull mj, chong a, et al. prediction of heart failure mortality in emergent care: a cohort study. annals of internal medicine. 2012;156(11):767-75. 4. miro o, gil v, martin-sanchez fj, herrero p, jacob j, sanchez c, et al. short-term reconsultation, hospitalisation, and death rates after discharge from the emergency department in patients with acute heart failure and analysis of the associated factors. the altur-ica study. medicina clínica (english edition). 2018;150(5):167-77. 5. ezekowitz ja, bakal ja, kaul p, westerhout cm, armstrong pw. acute heart failure in the emergency department: short and long-term outcomes of elderly patients with heart failure. european journal of heart failure. 2008;10(3):308-14. 6. lee ds, schull mj, alter da, austin pc, laupacis a, chong a, et al. early deaths in patients with heart failure discharged from the emergency department: a population-based analysis. circulation: heart failure. 2010;3(2):228-35. 7. mebazaa a, yilmaz mb, levy p, ponikowski p, peacock wf, laribi s, et al. recommendations on pre-hospital and early hospital management of acute heart failure: a consensus paper from the heart failure association of the european society of cardiology, the european society of emergency medicine and the society of academic emergency medicine–short version. european heart journal. 2015;36(30):1958-66. 8. king m, kingery je, casey b. diagnosis and evaluation of heart failure. american family physician. 2012;85(12):1161-8. 9. mullens w, damman k, harjola vp, mebazaa a, brunnerla rocca hp, martens p, et al. the use of diuretics in heart failure with congestion—a position statement from the heart failure association of the european sothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and k. keeratipongpun 8 ciety of cardiology. european journal of heart failure. 2019;21(2):137-55. 10. abebe tb, gebreyohannes ea, tefera yg, bhagavathula as, erku da, belachew sa, et al. the prognosis of heart failure patients: does sodium level play a significant role? plos one. 2018;13(11):e0207242. 11. matsue y, damman k, voors aa, kagiyama n, yamaguchi t, kuroda s, et al. time-to-furosemide treatment and mortality in patients hospitalized with acute heart failure. journal of the american college of cardiology. 2017;69(25):3042-51. 12. maisel as, peacock wf, mcmullin n, jessie r, fonarow gc, wynne j, et al. timing of immunoreactive b-type natriuretic peptide levels and treatment delay in acute decompensated heart failure: an adhere (acute decompensated heart failure national registry) analysis. journal of the american college of cardiology. 2008;52(7):534-40. 13. vansuch m, naessens jm, stroebel rj, huddleston jm, williams ar. effect of discharge instructions on readmission of hospitalised patients with heart failure: do all of the joint commission on accreditation of healthcare organizations heart failure core measures reflect better care? bmj quality & safety. 2006;15(6):414-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 1 emergency (2014); 2(1): 1-11 review article the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis alireza baratloo1, saeed safari1, alaleh rouhipour2, behrooz hashemi1, farhad rahmati1, maryam motamedi1, mohammadmehdi forouzanfar1, pauline haroutunian1* 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of pediatrics, valeeasr hospital, ghazvin university of medical sciences, abyek, iran abstract introduction: oral contraceptives (ocs) are considered as one of the most common risk factor of venous thromboembolism (vte) in childbearing age. some of the recent researches indicate that the odds of vte may be even higher with newer generations of ocs. the present meta-analysis was designed to evaluate the effect of different generation of ocs on the occurrence of vte. methods: two researchers independently ran a thorough search in pubmed, isi web of science, embase, cinahl and scopus databases regarding study keywords including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic and thrombosis, combined with oral contraceptive. the outcomes were the incidence of diagnosed thromboembolism, such as deep vein thrombosis, pulmonary embolism and cerebral venous thrombosis. based on the heterogeneity of the studies, random effect model was used and pooled odds ratio was reported. results: three cohort and 17 case-control studies with 13,265,228 subjects were entered into meta-analysis. analysis showed that the odds of vte in women taking ocs are more than three-fold (or=3.13; 95% ci: 2.61-3.65). the risk of vte in women taking first-, secondand thirdgeneration ocs are 3.5 fold (or=3.48; 95% ci: 2.01-4.94), 3 fold (or=3.08; 95% ci: 2.43-3.74) and 4.3 fold (or=4.35; ci: 3.69‒5.01), respectively. conclusion: it seems that the risk of vte is not same between different generations of ocs, so that third-generation has highest risk. taking second and third-generation ocs increases the risk of vte up to 3 and 4.3 fold, respectively. the researchers of the present study suggest that more trials be designed in relation to the effect of newer generations of ocs in different communities. key words: oral contraceptives; venous thromboembolism; intracranial thrombosis; pulmonary embolism; meta-analysis cite this article as: baratloo a, safari s, rouhipour a, et al. the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis. emergency. 2014;2(1):1-11. introduction:1 hromboembolic events are multifactorial phenomena, involving both genetic and acquired factors (1). some of the genetic factors include defects in and mutations of the genes of prothrombin and factor v leiden (2-4), whereas acquired factors include pregnancy, the postpartum period, obesity, lack of activity, and aging (5-8). at present, oral contraceptives (ocs) are considered one of the most common risk factors of venous thromboembolism (vte) in women at childbearing age. ocs are among the most commonly used methods to prevent pregnancy. the official reports of 2012 show that ocs have been used by 11 million women (17%) in the united states and 100 million women worldwide (9, 10). these pills may have lifethreatening side effects, including myocardial infarc *corresponding author: pauline haroutunian, md. 4th apartment, no. 6, 10th street, shahnazari avenue, madar square, mirdamad, tehran, iran. postal code: 1547735711. tel: +989126080530, fax: +982122721155. email: pauline_e25@hotmail.com. received: 30 december 2013; accepted: 15 january 2014 tion, strokes, and vte (11), and the odds of such incidents in women taking ocs are three times higher than those in nonusers (12-14). in recent decades, the chemical composition of ocs has undergone changes. compounds containing estrogen are known as important risk factors for this medical condition in postmenopausal women (15, 16). in this context, the estrogen content of ocs was decreased and new progestins were incorporated. despite these changes, the incidence of vascular complications resulting from the use of these pills is still high (17, 18). a meta-analysis of observational studies and clinical trials on postmenopausal women showed that the use of ocs containing estrogen increased the risk of vte by up to three fold, which significantly increased in the first year of the drug use and when combined with other risk factors (15). furthermore, the newer generation ocs presented higher odds of a vte risk, when compared with the older generation ocs (2, 12, 19). therefore, the present meta-analysis was designed to evaluate the effects of different generations of ocs on the incidence of vte. t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 2 emergency (2014); 2 (1): 1-11 figure 1: the flowchart of the study.  methods: this study was designed based on the instructions for conducting meta-analysis of observational studies in epidemiology statement (20). search strategy two independent reviewers conducted an extensive search in various databases. all the articles indexed in the electronic databases of pubmed, isi web of sciences, embase, cinahl, and scopus from 2000 to 2012 were evaluated. the keywords were determined by using the medical subject headings (mesh) of pubmed, which consisted of words related to “thrombosis,” including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic, and thrombosis, combined with oral contraceptive. only articles in english were evaluated. to evaluate additional articles with unpublished data, hand search was carried out in the list of “relevant studies.” selection criteria the cohort and case-control studies conducted on 15– 50-year-old female subjects, who took oral contraceptives, were included. the inclusion criteria were as follows: 1) study population consisting of subjects taking oral contraceptives; 2) studies in which the clinical outcomes, including deep vein thrombosis (dvt), pulmonary embolism (pe), and cerebral venous thrombosis (cvt) had been evaluated; 3) studies in which diagnosis of thromboembolism had been carried out by using standard and well-validated diagnostic criteria; and 4) studies with a nonuser control group. studies that were conducted before 2000, related to special populations such as postpartum, and of editorial, review, and letter to the editor types were excluded. quality assessment and data extraction the summaries of the studies were independently evaluated and recorded in data sheets by the two reviewers. the data were collected in a blind manner in relation to the authors, journal, and organization or institution. the reason for exclusion was recorded and disagreement was resolved by a third reviewer. the number of subjects, adjusted odds ratio (or), relative risk (rr), and rate ratio with 95% confidence interval (ci) were extracted from the relevant studies. if it was not possible to extract data from a study, the corresponding author was asked to provide the necessary data. the data and results in relation to the generation of ocs were recorded separately. finally, the findings were incorporated into a flowchart designed based on preferred reporting items for systematic reviews and metaanalyses (prisma) statement guidelines (21). data synthesis the outcomes consisted of dvt, pe, and cvt. three cohort (22-24) and 17 case-control studies (2-4, 14, 19, 25-36) met the inclusion criteria. one study had calculated the rate ratios (23), one had determined the rr (24) and the others had evaluated the or (2-4, 14, 19, 22, 25-36). as the type of the study had no effect on the results, based on a logistic regression model, all the 20 articles were included into one meta-analysis. in the sensitivity analysis, only studies with quality rates of good and fair were included. the funnel plot was used to evaluate selection bias (37) and “trim and fill” technique was used to identify publication bias (38, 39). the methods guide for effectiveness and comparative effectiveness reviews of the agency for healthcare research and 2378 article excluded not relevant (n= 2170) editorials/commentaries (n= 51) review articles (n= 157) 10 full-text articles excluded duplicate reports (n=4) data non-extractable (n= 1) without a non-user control group (n= 5) articles identified through database searching (n=5141) medline (2000dec 2012) n=1310 web of science (2000dec 2012) n=797 scopus (2000dec 2012) n=828 cinahl (2000dec 2012) n=422 embase (2000dec 2012) n=1784 duplicate omitted 2408 records screened 30 potentially eligible studies data from 20 studies analyzed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 3 baratloo et al quality was used to evaluate the quality of the studies (40). the reviewers evaluated each study in relation to its design, presence of bias in the selection of samples, and performance and reporting of outcomes. each study was given a general score of good, fair, or poor. studies with the least bias were given a score of “good;” studies in which there was a possibility of bias, but their results had not been influenced, were given a score of “fair;” and studies with obvious indications of bias and elimination of large amounts of data or great discrepancies in reporting the outcomes were given a general score of “poor.” the inter-rater reliability of the two reviewers was 83%. chi-squared and i2 tests were used to evaluate the heterogeneity among the studies, and statistical significance was defined at p < 0.1. if the studies were homogeneous, then the fixed effect model was used; otherwise, meta-analysis was conducted based on the random effect model. the results of the studies were pooled and an overall or was calculated, which indicated the odds of affliction with thromboembolism in women taking ocs, when compared with that in nonusers. the calculated or was also presented separately in relation to the generation of ocs. as meta-analyses were performed in at least three studies in which or had been presented, it was not possible to report the or for the fourth-generation ocs. statistical analyses were carried out by stata 11.0 (stata corporation, college station, tx). results: after elimination of duplicate reports, 162 potentially relevant articles were identified (figure 1). a total of 20 articles (13,265,228 subjects) were included in the meta-analysis, consisting of three cohort (22-24) and 17 case-control studies (2-4, 14, 19, 25-36) (table 1 and figure 1). five studies had evaluated the relationship between first-generation ocs and vte (4, 14, 24, 30, 32); eight studies had examined the second-generation ocs (4, 14, 19, 23, 24, 29-32) and seven studies had investigated the third-generation ocs (14, 19, 23, 24, 29, 30, 32). the endpoint of all these studies was the occurrence of dvt, pulmonary embolism, and cerebral embolism. the diagnostic tests used were doppler ultrasound for dvt and computed tomography angiography for pulmonary and cerebral embolism. logistic regression analysis showed the feasibility of pooling the studies (p = 0.12). heterogeneity and publication bias the studies included in the meta-analysis were not sufficiently homogeneous to allow conducting metaanalysis based on the fixed effect model. therefore, in all the analyses, random effect model was used. there were no selection and publication biases in three of the four meta-analyses (one meta-analysis of the firstgeneration ocs had publication bias). the limited number of studies (five studies) did not allow the exclusion of outlier studies to eliminate bias. the results of these four meta-analyses were as follows. meta-analysis a) effect of ocs on incidence of vte (without generation consideration) systematic review of 19 studies showed an or/rr range of 1.32–8.45, which was statistically significant (2-4, 14, 19, 22-36). only one study did not indicate an increase in the or (3). the meta-analysis showed that the odds of vte in women taking ocs was threefold higher than that in nonusers (or = 3.13; 95% ci: 2.61–3.65) (figure 2). b) effect of first-generation ocs on incidence of vte all the five studies on the relationship between the incidence of vte and first-generation ocs showed a high or (26,327 users and 5,909,630 nonusers). of these five studies, four were case-control (4, 14, 30, 32) and one was cohort (24). this increased risk was significant in four studies (4, 14, 30, 32). the adjusted or range in the studies was 1.57–8.1. the meta-analysis showed that the odds of vte in women taking first-generation ocs was 3.5-fold higher than that in nonusers (or = 3.48; 95% ci: 2.01–4.94) (figure 3). c) effect of second-generation ocs on incidence of vte the eight relevant studies indicated a significant relationship between the second-generation ocs and vte (4, 14, 19, 23, 24, 29, 30, 32). among these studies (2,537,189 users and 10,703,873 nonusers), six were case-control (4, 14, 19, 29, 30, 32) and two were cohort (23, 24). separate subgroup analysis of the study type showed that the overall or reported in the case-control studies was 3.57 (95% ci: 2.92–4.2) and the rr reported in the two cohort studies was 2.09 (95% ci: 1.82–2.34). the overall or for the incidence of vte in the secondgeneration oc users was 3.08 (95% ci: 2.43–3.74) (figure 4). d) effect of third-generation ocs on incidence of vte seven studies (2,536,993 users and 10,703,127 nonusers) had evaluated the effects of third-generation ocs on the incidence of vte (14, 19, 23, 24, 29, 30, 32). among these, five were case-control (4, 14, 19, 29, 30, 32) and two were cohort (23, 24). subgroup analysis based on the type of the study showed an or range of 3.39–7.7 (overall or = 4.74; ci: 3.42–6.08). the rr calculated from the two cohort studies were 4.0 and 4.47, respectively. the pooled analysis of all the seven studies showed an or of 4.35 (ci: 3.69–5.01) (figure 5). discussion: the results of this meta-analysis showed that ocs are important risk factors for vte in women. the risk of such events was higher with the use of third-generation ocs, as evidenced by other meta-analyses (41-43). a study performed in 2001 showed that the risk of vte in women taking third-generation ocs was 1.7-fold higher than that in women taking second-generation ocs (42). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 4 emergency (2014); 2 (1): 1-11 table 1: studies of oral contraceptive use, thrombosis and thromboembolism event  authors, year and location of study no. of cases/controls results adjustments weaknesses quality case-control studies austin et al., 2009 (25) usa 46 cases and 170 controls the risk of vte: or=2.6 age and household income analysis was not adjusted for other potential confounders small sample size. the participation rate of cases and controls was low selection bias: the use of clinic controls may result in an overestimate of ocs. fair aznar et al., 2000 (26) spain 84 cases and 89 controls the risk of vte: healthy users: or= 3.5 suspected thrombophilia: or= 14.3 dvt patients: or=6.9 none unadjusted analysis for potential confounders. the participation rate of cases and controls was low. fair barsoum et al., 2010 (34) usa 125 cases and 143 controls the risk of vte: total: or=3.0 estrogen alone: or=1.81 progestin alone: or=2.53 (ns) nonestrogen ocs plus progestin: or=2.53 age, bmi and all previously identified vte risk factors the participation rate of cases and controls was low. findings may not be generalizable to other races or ethnicities. sample size was too small to test the effect of different estrogen and progestin combinations, doses. good bergendal et al., 2012 (33) sweden 766 cases and 674 controls use of chc was associated with an eight-fold increased risk of vte: or=8.45 no risk increase associated with use of poc: or=0.98 use of mht increased risk for vte: or=3.73 age, bmi, smoking, use of hormones, bed rest/minor trauma, surgery, cast, surgery and cast, the prothrombin mutation and/or factor v leiden the participation rate of cases and controls was low. retrospective design. higher non-participant rate among the controls. possible recall-bias. no specified diagnostic criteria for assessment of menopausal status. fair bloemenkamp et al., 2000 (27) netherlands 155 cases and 169 controls the risk of dvt in healthy user: first six month of use: or=3.0 first years of use: or=2.0 the risk of development of dvt in combined with thrombophilia: first six month of use: or=18.5 first years of use: or=11.0 age, family history of venous thrombosis, history of pregnancy the most important genetic risk factors for venous thrombosis were not discovered. large confidence intervals. the participation rate of cases and controls was low. good vte: venous thromboembolism; dvt: deep vein thrombosis; vt: venous thrombosis; chc: combined hormonal contraceptives; poc: progestogen-only contraception; mht: multi hormone therapy; ns: non-significant; cee: conjugated equine estrogen; bmi: body mass index this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 5 baratloo et al table 1: studies of oral contraceptive use, thrombosis and thromboembolism event (continue)  authors, year and location of study no. of cases/controls results adjustments weaknesses quality dinger et al., 2010 (28) germany 680 cases and 2,720 controls the risk of vte associated with current coc use: or=2.3 dng/ee vs. any other low-dose cocs: or=0.9 dng/ee vs. low-dose lng/ee: or=1.1 drsp/ee vs. low-dose lng/ee: or=1.0 personal history of vte, family history of vte, body mass index, duration of combined oral contraceptive use, parity, educational level, chronic disease, concomitant medication and smoking recruit only survivors of vte. possible recall bias. good heinemann et al., 2002 (30) germany 605 cases and 2,941 controls the risk of vte: for all cases: or=3.4 for hospital cases: or=3.7 the risk of idiopathic vte: for all cases: or=5.4 for hospital cases:or=9.1 age, bmi, parity, ever-use of ocs did not assess of other potential confounder. good heinemann et al., 2010 (29) austria 362 cases and 1,505 controls the risk of vte: ocs containing gestodene: or=3.39 ocs containing progestin: or=3.14 age, bmi, parity and ever-use of hormonal contraceptives limit the generalizability of results to other regions and/or other racial and ethnic groups. mild or atypical vte cases were underreported in this study. good legnani et al., 2002 (2) italy 301 cases and 650 controls the risk of dvt: in the absence of both mutations was : or=2·4 in the presence of r506q mutation: or=41·0, in the presence of g20210a mutation: or=58·6 both mutations: or=86·5. age and presence of other thrombophilic defects lack of reporting of other potential confounders. good lidegaard et al., 2002 (14) denmark 654 cases and 1,921 controls the risk of vte: second generation ocs: or=2.9 third generation ocs: or=4.0 age, year, family history of vte, bmi, years of schooling, smoking, diabetes, coagulation disturbances, and previous delivery analysis was not adjusted for duration of use and other potential confounders. fair pomp et al., 2008 (31) netherlands 362 cases and 357 controls the risk of vte: current smokers and ocs users: or= 8.8 non-smoker and ocs user: or=3.9 age, sex, bmi, parity and fibrinogen levels the participation rate of cases and controls was low. fair santamaria et al., 2001 (3) spain 100 cases and 273 controls the risk of vte: without defect: or=1.3 (ns) pt20210a mutation+ ocs use: or=2.9 factor v leiden carriers + ocs: or=1.2 (ns) age, including the pt20210-a and the fvl mutations sample size was too small self-report of ocs use. unadjusted analysis for other potential confounders. good vte: venous thromboembolism; dvt: deep vein thrombosis; vt: venous thrombosis; chc: combined hormonal contraceptives; poc: progestogen-only contraception; mht: multi hormone therapy; ns: non-significant; cee: conjugated equine estrogen; bmi: body mass index this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 6 emergency (2014); 2 (1): 1-11 table 1: studies of oral contraceptive use, thrombosis and thromboembolism event (continue)  authors, year and location of study no. of cases/controls results adjustments weaknesses quality santamaria et al., 2001 (3) spain 100 cases and 273 controls the risk of vte: without defect: or=1.3 (ns) pt20210a mutation+ ocs use: or=2.9 factor v leiden carriers + ocs: or=1.2 (ns) age, including the pt20210a and the fvl mutations sample size was too small self-report of ocs use. unadjusted analysis for other potential confounders. good sidney et al., 2004 (4) usa 196 cases and 746 controls the risk of dvt: ocs user: or=4.07 factor v leiden mutation: or=7.1 prothrombin mutation: or=2.83 mthfr c677t mutation: or=0.26 age, race/ethnicity, income and bmi possible recall bias and diagnostic bias. unadjusted analysis for potential confounders. fair smith et al., 2004 (35) usa 493 cases and 1728 controls the risk of vte: total: or= 1.75 estrogen only: or: 0.92 (ns) cee: or: 1.65 cee + progestin:or: 2.17 age, hypertension, calendar year, race, and cancer history use of hormone therapy was not randomly assigned. findings are generalizable only to similar populations. good suissa et al., 2000 (19) germany and uk 128 cases and 650 controls the risk of vte: second generation ocs: rr=4.7 third generation ocs: rr=2.9 age, country, bmi, alcohol, smoking and duration of use defect in randomization. fair van hylckama et l., 2009 (32) netherlands 1,524 cases and 1,760 controls the risk of dvt: total:or= 5.0 ocs containing levonorgestrel: or=3.6 ocs containing gestodene: or=5.6 ocs containing desogestrel: or=7.3 ocs containing cyproterone acetate: or=6.8 ocs containing drospirenone: or=6.3 age and period of inclusion unadjusted analysis for potential confounders. the participation rate of cases and controls was low. potential recall bias. good cohort studies huerta et al., 2007 (22) uk 5,866 ocs users and 9,326 non-user the risk of vte in ocs users and hormone therapy group was same: rr=1.9 sex, age, calendar year, bmi, smoking, cancer, fractures in the last month, surgery in the last 6 months, use of warfarin sodium, the authors did not calculate the incidence of vte by weighting the number of newly diagnosed vte cases identified by the confirmation rate obtained in the validation study. good lidegaard et al., 2009 (23) denmark 2,302,045 ocs users and 4,802,168 nonuser the risk of vte: <1 year: rr=4.17 1-4 years: rr= 2.98 >4 years: rr= 2.76 current use of oral contraceptives, calendar year, and educational level family predisposition and body mass index were not adjusted. validity of each included diagnosis of vte was not checked. good lidegaard et al., 2011 (24) denmark 231,675 ocs users and 5,892,182 nonuser the risk of vte compared with users of combined oral contraceptives containing levonorgestrel: transdermal patches: rr=2.3 the vaginal ring: rr=1.9 age, calendar year, and education analysis could not control for family disposition or for bmi. good vte: venous thromboembolism; dvt: deep vein thrombosis; vt: venous thrombosis; chc: combined hormonal contraceptives; poc: progestogen-only contraception; mht: multi hormone therapy; ns: non-significant; cee: conjugated equine estrogen; bmi: body mass index this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 7 baratloo et al figure 2: odds ratio of the incidence of venous thromboembolism due to the use of ocp compared to non-users.  figure 3: evaluation of the or of venous thromboembolism in women taking first-generation ocs compared to non-users.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 8 emergency (2014); 2 (1): 1-11 figure 4: evaluation of the or of venous thromboembolism in women taking second-generation ocs.  figure 5: evaluation of the or of venous thromboembolism in women taking third-generation ocs.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 9 baratloo et al a similar result was also reported by martinez et al., who demonstrated that the risk of vte associated with third-generation ocs was greater than that associated with second-generation ocs (43). a review of the literature and meta-analysis of 19 casecontrol and cohort studies showed that, in general, the use of ocs increased the odds of vte by almost threefold, when compared with the nonusers (11). these or values are consistent with the results obtained in the present study. although the duration of drug use was different, in the present meta-analysis, vte frequently occurred in the first year of use. previous studies have demonstrated that the incidence of vte was higher in women who recently started taking ocs (23, 44-46). quality issue in the present study, the application of three techniques resulted in qualitative confirmation of meta-analysis. initially, subgroup analysis was carried out separately for each generation of ocs. in this context, only confirmed and documented cases of thrombosis were included in the meta-analysis. in the second stage, to evaluate the implementation of appropriate adjustments for confounding factors, or was separately calculated for approximate or or rr and was adjusted. as the or calculated from both the analyses were almost the same, the presence of a confounding factor was unlikely. therefore, only adjusted or or rr was reported. in addition, in the present meta-analysis, only women at childbearing age (age under 50 years) were included, which eliminated the effect of age. in the third stage, the quality assessment of exposure was evaluated, which was conducted by separating the different generations of ocs. although the definitions of drug generations were not completely similar in the included studies, they did not affect the pooled or, because of the much less weight of studies with incongruent definitions (4, 19, 30, 32) (figure 2-4). however, the calculated pooled or might have been underestimated; because (i) it was not possible to completely eliminate publication bias, particularly in the case of or calculated for the firstgeneration ocs; (ii) some pharmaceutical companies might refrain from disclosing the results of studies to protect personal benefits, resulting in an increase in publication bias (47); and (iii) the use of rr calculated from the community data (especially from cohort studies) is generally less frequent, when compared with the results obtained from matched regression analyses. furthermore, the differences in the incidence rate of vte with the use of first-, second-, and thirdgeneration ocs might be attributed to the differences in the populations of women taking these drugs, because new users have a tendency to use new generations, but old users prefer to use the same drug that they had been using. moreover, new users might consist of women who are genetically predisposed to vte or have an acquired susceptibility to vte. in this context, it has been shown that older users are resistant to the complications of the drug, which might result in erroneously reporting a higher risk of vte in newer generations, when compared with older generations. however, as drug use duration had not been adjusted only in one study (14) the presence of confounding factors was very improbable. limitation one of the most important limitations of the present study was the meta-analysis nature of the observational studies. the observational studies, with their inherent limitation for the evaluation of all the confounding factors, could not reliably establish the cause-and-effect relationships. another limitation was the heterogeneity of the studies, resulting in designing of meta-analyses based on random effect model. although an attempt was made to choose studies similar in methodology and to control the confounding factors, this aim could not be completely achieved even under ideal conditions. therefore, in the present meta-analysis, the definitions, controls for confounding factors, and study populations in the studies included were different to some extent. for example, the methods used to diagnose and confirm thromboembolism in the selected studies were not similar. although only the data of confirmed cases were included in the meta-analyses, as the diagnosis of thromboembolism was hampered by limitations, some patients might have been erroneously classified, thus influencing the results. advantages in the present study, the databases were extensive searched and attempts were made to contact the corresponding authors for acquisition of data. more importantly, apart from evaluation of the effects of all the ocs, the results were reported separately for all the three generations of ocs. this analysis significantly contributed to decreasing bias, and among the four analyses, only one had selection and publication biases. another advantage of the present study was the elimination of data of switchers (women who changed the drug that they used owing to pooled side effects) because changing of the drug has been reported to increase the risk of vte (19). conclusion: it seems that the risk of vte was not the same between different generations of ocs, with third-generation ocs presenting the highest risk. the use of secondand third-generation ocs increased the risk of vte by up to threefold and 4.3-fold, respectively. nevertheless, further clinical trials in relation to the effect of newer generations of ocs on different communities are necessary. acknowledgments: we thank dr. mahmoud yousefifard who kindly helped us in revising this manuscript. this work is a part of the academic thesis of dr pauline haroutunian in shahid beheshti university of medical sciences. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 10 emergency (2014); 2 (1): 1-11 conflict of interest: all authors declare no conflict of interest. funding support: none declared. authors’ contributions: alireza baratloo and pauline haroutunian are the principle investigators; farhad rahmati, maryam motamedi, mohammadmehdi forouzanfar, and behrooz hashemi are the co-investigators who collected the basic data; pauline haroutunian wrote the first draft and collected data with internet research; saeed safari and alaleh rouhipour commented on the final manuscript; and alireza baratloo provided critical revisions. references: 1. rosendaal fr. risk factors for venous thrombosis: prevalence, risk, and interaction. semin hematol. 1997;34(3):171-6. 2. 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hernandez rk, jick ss. risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on uk general practice research database. bmj. 2011;342:d2139. 47. weber w. maastricht study on risks of third wim weber generation pill “kept secret by industry”. the lancet. 2001; 357(9258):779-85. http://www.effectivehealthcare.ahrq.gov/ emergency. 2017; 5 (1): e10 or i g i n a l re s e a rc h epidemiological pattern of injuries in iran; a nationwide review of seven million emergency department admissions mohammad haji aghajani1, mashyaneh haddadi2, soheil saadat3,4∗ 1. department of cardiology, shahid beheshti university of medical sciences, tehran, iran. 2. injury prevention and safety promotion department, ministry of health and medical education, tehran, iran. 3. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. 4. e-health department, virtual school, tehran university of medical sciences, tehran, iran. received: may 2016; accepted: may 2016; published online: 8 january 2017 abstract: introduction: globally, it is estimated that around 5.8 million people die annually as result of injuries, which causes 10% of all deaths and 16% of disability adjusted life years lost worldwide. this study aimed to determine the epidemiology of injuries in emergency departments in iran. methods: this cross sectional study was carried out using national injury surveillance data registry from 21 march 2009 to 20 march 2014. results: 7,176,344 patients with the mean age of 27.5 ± 17.8 years were registered to 657 eds (70.6% male). road traffic crash (rtc) was the most common cause of injury (31.0%) followed by hit (28.2%) and fall (10.1%). while roads were the commonest place of injuries, 34.0% of patients have been injured at home. more than 90% of injuries were unintentional. assault and suicide attempt were causes of injury in 5.6% and 3.9% of patients, respectively. conclusion: this paper addresses where prevention measures are most urgently needed and offers insights which could be useful for injury prevention programs in iran and other developing countries. keywords: epidemiology; wounds and injuries; epidemiological monitoring; multiple trauma; mortality; accident prevention © copyright (2017) shahid beheshti university of medical sciences cite this article as: haji aghajani m, haddadi m, saadat s. epidemiological pattern of injuries in iran; a nationwide review of seven million emergency department admissions. emergency. 2017; 5 (1): e10. 1. introduction globally, it is estimated that around 5.8 million people die annually as result of injuries, which causes 10% of all deaths and 16% of the disability adjusted life years (daly) lost worldwide (1). injury-related disease burden is expected to rise over the next 20 years and road traffic injuries, suicide and falls which are known as 9th, 15th and 21st leading causes of death are respectively estimated to rise to 5th, 12th and 16th cause of death by 2030 (2). ninety percent of all injuryrelated deaths occur in low and middle-income countries, whose limited data collection is hampering planning and implementation of preventive measures (3). injuries are an im∗corresponding author: soheil saadat; 2nd floor, sina trauma and surgery research center, sina general hospital, hassan-abad sq., imam-khomeini ave., tehran, iran. tel/fax: 009866757001; email: soheilsaadat@tums.ac.ir portant challenge for the health system and account for 28% of the daly lost (21,572) in iran (4). iran is in the 5th place for road traffic mortality rate globally, and has the highest mortality rate in eastern mediterranean region (5). although death is the most notable measure of injury, it represents just the tip of the iceberg and to address the problem, data of both fatal and nonfatal injuries are required as non-fatal injuries are quite common and impose huge medical expenses on the population (6). injury surveillance is the ongoing systematic collection, analysis, interpretation and dissemination of data for planning, implementing, monitoring and evaluation of preventive interventions (7). the absence of reliable estimations on the scale and pattern of injury morbidity and mortality is a major barrier to successfully implement preventive strategies in many low and middle-income countries (8, 9). this study aims to determine the epidemiological pattern of injuries during five years using the national injury surveilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haji aghajani et al. 2 lance data registry. 2. methods 2.1. study design and setting this cross sectional study was designed to evaluate the epidemiological pattern of injuries among almost all trauma patients presented to the emergency departments (ed) of university hospitals in iran, between 21 march 2009 and 20 march 2014, using an ed based injury surveillance data registry. the study was approved by ethical committee of ministry of health and researchers adhered to all ethical principles of helsinki declaration and patient data confidentiality during the study period. 2.2. data gathering to monitor the frequency of fatal and non-fatal injuries on an ongoing basis, identify high-risk groups requiring specific interventions; monitor and evaluate interventions for effectiveness, and produce reports to assist in planning and resource allocation, an ed based injury surveillance data registry system has been established in the iranian ministry of health and medical education in 2004. the system has been further developed in 2005 by including all medical university hospitals (10). the data gathering process commences when injured patients arrive at an ed. information is registered on the medical records by the medical staff and no medical doctors are involved. at the end of stay in the ed, data are added to a paper based questionnaire and then into the electronic offline software which is installed in most public university hospitals. for hospitals in which the software is not installed, the paper based data is converted into electronic format and retained by the corresponding medical university. quality control is performed by injury prevention experts from universities and the ministry of health (11). university hospitals are obliged to register all admitted injured patients; however, we cannot ignore possibility of underreporting in some cases. therefore, we did not use the data to estimate injury incidence rate in the iranian population. the dataset includes demographic data (age, sex), injury characteristics (time, place, mechanism), and patients outcome at the end of ed stay. the injury characteristics were registered according to who injury surveillance guideline. data of the present study were extracted from the afore-mentioned national registry, using census sampling. 2.3. statistical analysis statistical analysis was performed using spss version 18. continuous variables are presented as mean ± standard deviation (sd) and discrete ones as frequency and percentage. table 1: cause of injury distribution case number (%) rtc 2225123 (31.0) hit 2026468 (28.2) fall 724506 (10.1) violence 402203 (5.6) poisoning 353999 (4.9) burn 305066 (4.3) suicide attempt 277563 (3.9) bites 127316 (1.8) animal attack 81871 (1.1) electric shock 23707 (0.3) drowning 4960 (0.1) others 623153 (8.7) unknown 409 (0.0) total 7176344 (100.0) rtc: road traffic crash. 3. results: 7,176,344 patients had been registered to 657 eds all around the country. mean age of the injured patients was 27.5 ± 17.8 years (0, 102) and 70.6% of the cases were male. figure 1 presents age and sex distribution of the injured patients. 3.1. injury characteristics table 1 summarizes the frequency of injury causes among the studied patients. road traffic crash (rtc) was the most common cause of injury (31.0%) followed by hit (28.2%) and fall (10.1%). among the patients injured due to rtc, 962,045 (43.3%) were car occupants, 862,429 (38.8%) motorcyclists, and 399,253 (18.0%) were pedestrians. frequency of violence and suicide attempt were 402203 (5.6%) and 277563 (3.9%), respectively. the relative frequency of intoxication and animal attacks as cause of injury showed a raise during the study period; while burn, suicide, rtc and bites presented with a decreasing trend (figure 2). 2,440,703 (34.0%) of patients had been injured at home and 700,789 (9.8%) at work places. figures 3 and 4 show the distribution of common causes of injury according to place of occurrence and the age group of the injured patients. most injuries had happened in urban areas (79.9%) followed by rural (12.8%) and intercity (5.8%). roadside was the most common place of injury with 3,008,072 (41.9%) cases. summer (28.8%) was the commonest season for emergency admission of injured patients followed by spring (26.6%), and winter (20.6%). 3.2. male to female ratio figure 5, displays the male to female (m/f) ratio in different age groups according to the cause of injury. overall, the highest m/f ratio was seen in patients injured due to violence and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e10 figure 1: age and sex distribution of the injured patients. in 15-25 years age group (8.3). the ratio was 3.3 for violence related injuries that took place in the street and public places, and 0.7 for violence related injuries that occurred at home, regardless of age groups. 3.3. mortality rate mortality rate in ed was 490, 443, 386, 383 and 387 per 100,000 cases in consecutive study years. it was highest in suicide attempts and in the elderly (figure 6). mortality rate in ed for injuries that occurred in urban, rural and intercity areas were 295, 702 and 1291 per 100,000 cases, respectively. 4. discussion: iran is one of the 77 countries that have a national injury surveillance system (iss). less than half of high and middleincome countries, and less than a quarter of low-income countries have established a nationwide iss (5). the current iranian national iss yet needs to be improved; however, it can help in understanding the epidemiology of severe injuries that require medical care throughout the country. iran with a population of 78.8 million in 2015 and land area of 1.6 million square kilometers (12) experiences the age standardized injury mortality of 74.9 per 100,000 population (13). according to findings of this study, all age groups have been affected by injuries with the highest frequency belonging to young males. a similar pattern has been reported in previous studies from iran, saudi arabia, and china. (11, 14, 15). however, case fatality of the injured in ed showed a raise in the elderly. this indicates that preventive programs should encompass all age groups; while elderly injured patients need specialized and intensive care in the ed. this should be considered in triage and referral protocols as old injured patients would better be referred to level-one trauma centers. rtc continues to be an increasing source of morbidity and mortality worldwide with the developing countries worst hit due this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haji aghajani et al. 4 figure 2: the relative frequency of causes of injury during the study period (dotted lines represent decreasing trend, dashed lines represent increasing trend and solid lines are used for steady trend), y axis is in logarithmic scale; rtc: road traffic crash. figure 3: distribution of common causes of injury according to place of occurrence; rtc: road traffic crash. to rapid unplanned industrialization and urbanization. our study, further highlights this fact by introducing rtc as the most common cause of injury, like previous studies (11, 16, 17). iran was experiencing an increasing trend in rtc fatality and injury rates until 2005 (18). the death rate due to rtc hit the global record of 44 per 100000 population in 2005 (19). conversely, from 2006 the trend was reversed (18-20) and annual rtc fatality rate dropped to 21.6 in 2014 according to official national road traffic safety status report by ministry of road & urban development. the relative frequency of rtc compared to other causes of injury showed a decreasing trend in our study. this could be a result of the preventive this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e10 table 2: the distribution of road traffic crash (rtc) injured patients according to the region and type of road user region position pedestrian car occupant motorcycle rider urban 354670 (22.5) 565392 (35.9) 653974 (41.5) rural 33568 (11.5) 111021 (38.1) 146910 (50.4) intercity 9537 (2.8) 278151 (81.0) 55535 (16.2) intercity 1478 (9.9) 7481 (50.0) 6010 (40.1) total 399253 (18.0) 962045 (43.3) 862429 (38.8) data were presented as number and percentage; the position of 1396 rtc injured patients was not known. figure 4: the leading causes of injury in different age groups (y axis is in logarithmic scale). programs for rtc in line with the international framework of the decade of action on road safety. iran has been committed to reduce road fatalities by 10% annually, according to the 5th five year development plan beginning in 2011. health sector aims to control injuries and promote safety through a balanced approach based on primary, secondary and tertiary prevention. increasing the number of emergency medical service (ems) stations, initiating the air ambulance services, renovating ems fleet as well as improving the quality of pre and in-hospital care are among health sector programs that contribute to reducing road fatalities. among road users, car occupants had the highest ed admission rate, followed by motorcyclists and pedestrians. this is similar to reports from comparable studies (11, 21). our study did not include onsite mortality cases; however, a national study that included all rtc mortalities for a decade, reported that about half of traffic mortality cases have been car occupants followed by motorcyclists and pedestrians (22). although pedestrians are the most vulnerable group in rtc, speeding makes car occupants the group most commonly referred to ed due to rtc. as seen in table 2 the proportion of car occupants is highest in rtcs occurred in intercity areas where speeding is possible, and least in urban areas where law enforcement and traffic jam makes it difficult to speed up. limiting the speed of driving according to the guidelines of vision zero (23) or sustainable safety program (24) should be considered by local authorities to reduce the number of road users injured due to rtc (25). motorcycle riders are the second most common injured group in rtc. a population based study has shown that although 19.7% of households owned a motorcycle in the capital of iran, the attributable risk of rtis due to motorcycles was 63.9% in 2008 (26). speed limit, using safety helmet and traffic law enforcement should be considered to protect both motorcyclists and pedestrians from rtc. although rtc was a major cause of injury in all ages, it appeared as the leading cause of injury in 15-75 years age groups. this is in line with other studies and points out the fact that rtc is clustered in active age groups. similarly, fall is a major cause of injury in all ages but it overrides other causes in ages older than 75. this pattern has been reported in population based studies as well (6). this is partly due to a decrease in rtc rate in the elderly as a result of reduced social activity and partly due to increased risk of falling in this population due to imbalance and osteoarthritis as a result of aging (6). population based interventions are required to increase the awareness of families about strategies to prevent the elderly from falling and keep old people as physically active as possible to improve their balance and body muscle mass. moreover, there is a need to monitor the adverse effect of medications they are using and also make suitable environmental modifications to prevent fall or limit its consequences. prevention and treatment of osteoporosis should be considered in every elderly who refers to health centers. roadside was found to be the leading place of injury occurrence followed by home. the findings of this study are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haji aghajani et al. 6 figure 5: male to female ratio of patients in different age groups according to the cause of injury. consistent with those of rastogi et al. (27), which is due to higher incidence of rti compared to other injuries. home being the second most common place of injury could be explained by the amount of the time spent at home and the vast variety of activities taking place there. majority of suicide attempts, intoxication, burns, fall and electric shock injuries occur at home. therefore, to reduce the incidence of above-mentioned injuries, interventions are needed. interventions should aim to increase the safety knowledge of families, raise the willingness of parents to pay for safety, and also provide affordable safety devices for low income famifigure 6: mortality rate in emergency department per 100 cases according to the age group; rtc: road traffic crash. lies. households that take care of children and elderly should be of priority in safety improvement interventions. violence was the cause of injury in 5.6% of ed admissions. in a similar study of ed admission from 2005 to 2008, violence was accountable for 5.2% of injuries (11). there is need for effective violence prevention interventions in the public to reduce this avoidable injury. streets are the place that majority of violence related injuries take place, followed by home and public places. as a result, violence prevention programs should be aimed at these places. violence in street and public places generally take place between strangers, usually incidentally and involve mainly males. this type of violence could be prevented by police interference and redesigning public areas to reduce the stress and conflict of society. however, violence prevention at home needs different strategies because this type of violence takes place between familiar people and involves females 2.4 times more than the violence occurred in public places and streets. this type of violence accounts for about 20% of violence injuries and needs special consideration. health sector has developed a policy paper on domestic violence to address intentional injuries. since the survivors of domestic violence not only need alternatives to returning home, risk assessment, and referrals for counseling, and legal services but also medical care including assurances that they were not at fault for the battering, a policy was developed in 2012 as a joint program bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e10 tween ministry of health and medical education and who office in iran to sensitize and increase health care providers awareness of domestic violence. suicide accounted for 3.9% of ed admissions. sharif-alhoseini et al. showed a similar proportion for suicide attempts in their study that included ed admissions from 2005-2008 in iran (28). there is a strong stigma for suicide in iran, which may result in underreporting of suicide attempts in ed. however, suicide is an avoidable injury and unlike most other injuries, there are medical approaches for its prevention. therefore, health sector may be able to control this type of injury by providing efficient mental health care to vulnerable patients. the fact that most suicide attempts took place at home, points out an opportunity for prevention, and highlights the importance of family oriented interventions in facing suicide attempt of a household member. suicide attempt has been more common in females aged five to sixty years, in contrast to most other injuries. therefore, young and middle aged females under 60 years old are in priority for suicide prevention. besides preventability, there is another reason to allocate resources to suicide prevention: it has the highest case fatality in ed in most age groups. health care personnel should be trained to identify people at risk of suicide attempt and health departments should establish programs to support at risk people and their families as well as health system staff to deal with a case at risk of suicide attempt. a training and service manual is prepared and implemented in university hospitals to increase the knowledge of ems staff, change their attitude, and be used as a guideline to approach aggressive, criminal and suicidal cases. work places are another common site of injury that account for about ten percent of ed admissions. there are occupational safety offices in medium and large work sites that supervise adherence to safety regulations in iran. however, small workshops do not benefit from such a professional safety promotion service and there is need for improvement in these sites. although 72.8% of the iranian population lives in cities in the year 2015, 79.9% of ed admissions due to injury had happened in urban areas. it is not clear whether higher presentation of urban patients is due to higher injury incidence in urban areas or as a result of limited access of rural population to eds. however, the higher injury fatality in rural area eds indicates the possibility of under-presenting moderate injuries from rural areas. in other words, patients injured in rural areas refer to ed only in very severe instances compared to urban patients and this may reflect inequality in trauma care. although, based on the 3rd five year development plan (2000) the government had become responsible for developing trauma system to provide optimum care for trauma patients free of charge, this system has not been implemented yet and only road traffic injured patients care is free of charge. based on the health evolution plan (2014) and changes in out of pocket payments, medical care has become more affordable for traumatic patients in rural areas. also, because of the long distances between hospitals in rural areas, injured patients who suffer from life threatening situations are referred to the nearest health care center to be stabilized and then referred to designated hospitals based on their medical requirements. in order to address different coverage of ems in urban and rural areas, remote and outreach areas, health sector scaled up the air ambulance system for better coverage in rural areas. in terms of seasonality, summer was the commonest season for emergency admission of injured patients followed by spring. this could be partly explained by the increased outdoor activity in the summer that increases the risk of fall, drowning and sport related injuries. on the other hand, rtc was the most common cause of injury and an increase in rtc due to increased road traffic for leisure purposes in spring and summer would reflect in the total number of injuries. most educational institutes are closed in the summer. therefore, students who had had to spend almost always in the school would engage in a lot of activities during the summer and they are not necessarily prepared for safety of leisure in this season. there is a need to increase the safety awareness of students before summer vacations and also improve the safety preparedness of the community before summer. the traffic police, road traffic maintenance organization, ems and red crescent take special effort to enforce traffic regulations and increase their road side capacity during the summer. moreover, health sector runs seaside rescue programs during this season for caspian sea. however, there are too many rivers and small pools to be covered by this program. moreover, there is not any fall prevention program during the summer season, when people may climb trees to harvest. there is also need for animal attack and insect bite prevention programs before beginning of warm seasons. educational institutes are best places to raise the safety knowledge of students, as a group who will involve in sport and leisure activities more than others. media can also play a crucial role. safe community movement is a community based approach that aims to reduce injuries and deaths by bringing together partners to tackle safety issues affecting the community. this approach encourages and supports aspiring communities to deliver local solutions for local concerns through a community-based coalition. at the moment, iran has 35 designated members in the international safe community network and there is a national commitment to expand the program (29). as seen in figure 1, injuries have been more common in males in all age groups, especially in young ages. meanwhile, the highest m:f ratio was seen in patients injured due to violence and in 1525 age group. males may get physical in this age group more than females. this points out the need for anger and bullying behavior control and interpersonal conflict management programs for this age-sex group that could be taught this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haji aghajani et al. 8 in high schools. these educations are not provided as part of routine training in iranian schools. high school students may also benefit from educations aimed to raise knowledge and improve the skill against substance abuse that may in turn reduce their involvement in violence, especially in male schools. the m:f ratio was the least in bites and burn injuries as well as intoxication. while some studies indicate burns were more common in females (30), others indicated slight male dominance for burns (31-34) and poisoning (56%) (35). there was a downward trend in case fatality among patients admitted to eds. the case fatality in 2013 was 21% lower than 2009. this is an evidence of improvement in trauma care in iran. obligatory current medical education (cme) programs aimed to improve the quality of trauma care, implementing hospital trauma quality improvement programs such as running morbidity & mortality conferences and fair and equitable distribution of emergency medicine physicians may have played a role in decreasing case fatality of traumatic patients admitted to eds. moreover, a significant growth in emergency medicine (em) residency programs boosted the number of em specialists now staffing eds throughout the country. these programs should be spread out more to improve the quality of trauma care in outreach areas. the disaster and emergency management center is going to implement an ongoing preventable trauma death (ptd) study that aims to monitor ptd in all university hospitals and provide prompt feedback to local health authorities, as another quality monitoring and improving program. this study has some limitations. injury-related deaths that occurred on the scene of trauma, or following transfer to other wards, an intensive care unit or operating theatre were not included in this study. moreover, data on external causes of injury, icd codes, causes of death, injury severity scores, and vital signs were not available since these data are usually recorded in trauma registry systems and not in the iss. more information is needed on the burden of disabilities due to injuries that can’t be extracted from the current ed based system. 5. limitations: we were not able to study the severity of injuries as well as the quality of care. this needs to be addressed in further studies. 6. conclusion: this paper addresses where prevention measures are most urgently needed and offers insights which could be useful for injury prevention programs in iran and other developing countries. 7. appendix 7.1. acknowledgements authors would like to acknowledge all medical staff who gathered the data. 7.2. authors contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the 4 criteria of authorship recommended by the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. peden m, mcgee k, sharma g. the injury chart book: a graphical overview of the global burden of injuries. geneva: world health organization. 2002;5. 2. organization wh. fatal injury 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afsari m, et al. suicide attempts and suicide in iran: results of national hospital surveillance data. public health. 2012;126(11):990-2. 29. members scn. who collaborating centre on community safety promotion [cited 2016 feb]. available from: http://www.ki.se/csp/who_safe_communities_network_ en.htm. 30. ganesamoni s, kate v, sadasivan j. epidemiology of hospitalized burn patients in a tertiary care hospital in south india. burns. 2010;36(3):422-9. 31. othman n, kendrick d, al-windi a. childhood burns in sulaimaniyah province, iraqi kurdistan: a prospective study of admissions and outpatients. burns. 2015;41(2):394-400. 32. han t-h, kim j-h, yang m-s, han k-w, han s-h, jung ja, et al. a retrospective analysis of 19,157 burns patients: 18-year experience from hallym burn center in seoul, korea. burns. 2005;31(4):465-70. 33. tyson af, boschini lp, kiser mm, samuel jc, mjuweni sn, cairns ba, et al. survival after burn in a subsaharan burn unit: challenges and opportunities. burns. 2013;39(8):1619-25. 34. sharma np, duke jm, lama bb, thapa b, dahal p, bariya nd, et al. descriptive epidemiology of unintentional burn injuries admitted to a tertiary-level government hospital in nepal gender-specific patterns. asia-pacific journal of public health. 2015;27(5):551-60. 35. burillo-putze g, munne p, duenas a, pinillos ma, naveiro jm, cobo j, et al. national multicentre study of acute intoxication in emergency departments of spain. european journal of emergency medicine. 2003;10(2):101-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 138 emergency (2014); 2 (3): 138-140 brief report diagnostic accuracy of ascites fluid gross appearance in detection of spontaneous bacterial peritonitis hamed aminiahidashti1, seyed mohammad hosseininejad1, hosein montazer1, farzad bozorgi1*, iraj goli khatir1, fateme jahanian1, behnaz raee2 1. department of emergency medicine, mazandaran university of medical sciences, sari, iran 2. department medical faculty, mazandaran university of medical sciences, sari, iran abstract introduction: spontaneous bacterial peritonitis (sbp) as a monomicrobial infection of ascites fluid is one of the most important causes of morbidity and mortality in cirrhotic patients. this study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of sbp in cirrhotic cases referred to the emergency department. methods: cirrhotic patients referred to the ed for the paracentesis of ascites fluid were enrolled. for all studied patients, the results of laboratory analysis and gross appearance of ascites fluid registered and reviewed by two emergency medicine specialists. the sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ration of the ascites fluid gross appearance in detection of sbp were measured with 95% confidence interval. results: the present project was performed in 80 cirrhotic patients with ascites (52.5 female). the mean of the subjects’ age was 56.25±12.21 years (35-81). laboratory findings revealed sbp in 23 (29%) cases. fifty nine (73%) cases had transparent ascites fluid appearance of whom 17 (29%) ones suffered from sbp. from 21 (26%) cases with opaque ascites appearance, 15 (71%) had sbp. the sensitivity and specificity of the ascites fluid appearance in detection of sbp were 46.88% (cl: 30.87-63.55) and 87.50% (95% cl: 75.394.14), respectively. conclusion: it seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of sbp and considering its low sensitivity, it could not be used as a good screening tool for this propose. key words: peritonitis; ascites; diagnostic tests, routine; mass screening cite this article as: aminiahidashti h, hosseininejad sm, montazer h, bozorgi f, goli khatir i, jahanian f, raee b. diagnostic accuracy of ascites fluid gross appearance in detection of spontaneous bacterial peritonitis. emergency. 2014;2(3):138-40. introduction: 1 pontaneous bacterial peritonitis (sbp) is one of the most important causes of mortality and morbidity in cirrhotic patients (1, 2). sbp is a monomicrobial infection of ascites fluid which has no determined source for surgery treatment (3, 4). it was the result of transferring the bacteria through the intestinal wall to mesenteric lymph nodes and then into ascites fluid (5, 6). 10% to 30% of cirrhotic patients hospitalized because of ascites are at risk for sbp (2, 3). with early detection and antibiotic treatment, quickly and timely, the mortality rate of sbp has decreased from 80% to 20-30% (4, 7, 8). the studies have shown that the most common types of microorganisms responsible for sbp arise from the enterobacteriaceae group like escherichia coli (e. coli) (1, 3, 9). sbp detection was done with observing more than 250 polymorphonuclears (pmn) or 500 white blood cells (wbc) per cubic millimeter of ascites fluid (4). assessment of ascites *corresponding author: farzad bozorgi; assistant professor, department of emergency medicine, imam khomeini hospital, amir mazandarani bolivar, sari, iran. tel: +989112582254; email: farzad722001@yahoo.com received: july 2014; accepted: july 2014 fluid with dipstick is a rapid, simple, and cost-effective method for classifying it into transudate and exudate(10). the color of abnormal ascites fluid has a high sensitivity in the confirmation of sbp so that with a transparent ascites fluid it can be rejected (11). on the other hand, in some studies it was revealed that sbp was rare in cirrhotic patients without symptoms (1214). however, not enough studies have been done regarding the correlation between ascites fluid color and sbp and there are different results in the previous studies. therefore, this study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of sbp in cirrhotic cases referred to the emergency department (ed). methods: it was a study of diagnostic methods. cirrhotic patients referred to the ed of emam khomeini hospital, sari, iran, through february 2011 to march 2013, for the paracentesis of ascites fluid were enrolled. the study protocol was approved by local ethic committee and in accordance with helsinki declaration. patients with ascites caused by another reason except liver cirrhosis were excluded. for all studied patients, the samples of s mailto:farzad722001@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 139 aminiahidashti et al ascites fluid were sent to the same reference laboratory for cell counting and biochemical analysis; then the results of laboratory and gross appearance registered and reviewed by two emergency medicine specialists. the gross appearance of ascites fluid included two groups of transparent or not. the transparent appearance was considered as the lack of sbp and other cases such as bloody, opaque, hazy, cloudy, or milky ascites fluid as the presence of sbp. more than 250 pmn or 500 wbc per cubic millimeter of ascites fluid was considered as sbp (4). in this project, no additional intervention was imposed to the patients. informed consent received from patients for entering to the study. all the costs of included subjects were free. the achieved data was statistically evaluated using spss version 20. the gross appearance and cell counting results were compared by chi-squared test. the sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), positive (plr), and negative likelihood ration (nlr) of the ascites fluid gross appearance in detection of sbp were measured with 95% confidence interval. results: the present project was performed in 80 cirrhotic patients referred to the ed for paracentesis of ascites fluid (52.5% female). the mean and standard deviation of the subjects was 56.25±12.21 years (range: 35-81). laboratory findings revealed sbp in 23 (29%) cases. the mean age of patients who suffered sbp was 57.09±19.30 and for those lack of sbp 55.68±15.76 years (p=0.6). fifty nine (73%) cases had transparent ascites fluid appearance of whom 17 (29%) ones suffered from sbp. from 21 (26%) cases with opaque ascites appearance, 15 (71%) had sbp. table 1 shows the results of diagnostic tests of ascites fluid appearance in detection of sbp. discussion: in this project the sensitivity and specificity of the ascites fluid appearance in detection of sbp were 46.88% (cl: 30.87-63.55) and 87.50% (95% cl: 75.3-94.14), respectively. gross appearance of sbp fluid had 71.25% (60.54-80.01) accuracy in sbp prediction. in the brian chinnock et al. study the sensitivity and specificity of the abnormal ascites color were reported 98% (95% cl: 95.3-99.5) and 22.7% (95% cl: 19.4-26.3), respectively (11). they declared that clear appearance of ascites fluid might safely exclude sbp. on the other hand, in other studies ascites fluid appearance had a low sensitivity in detection of sbp (15, 16). they concluded that the gross appearance of ascites fluid is insufficient for diagnosis or exclusion of sbp and suggested the routine laboratory analysis of ascites fluid for rule in/out of sbp. considering the low sensitivity and npv of ascites fluid color in sbp detection, it is not possible to detect or reject sbp using the gross appearance of ascites fluid. it was suggested to perform this study with more sample size and in several centers for getting more convincing results. conclusion: it seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of sbp and considering its low sensitivity, it could not be used as a good screening tool for this propose. acknowledgments: we would like to thank all the emergency department staffs of imam khomeini hospital, sari, iran. conflict of interest: none funding support: none authors’ contributions: none references: 1. ginès p, angeli p, lenz k, et al. easl clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. j hepatol. 2010;53(3):397-417. 2. angeloni s, leboffe c, parente a, et al. efficacy of current guidelines for the treatment of spontaneous bacterial peritonitis in the clinical practice. world j gastroenterol. 2008;14(17):2757-62. 3. lee jm, han kh, ahn sh. ascites and spontaneous bacterial peritonitis: an asian perspective. j gastroenterol hepatol. 2009;24(9):1494-503. 4. garcia–tsao g. current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. gastroenterology. 2001;120(3):726-48. table 1: the results of diagnostic tests of ascites fluid appearance in detection of spontaneous bacterial peritonitis  diagnostic tests value (%) 95% confidence interval accuracy 71.2 60.5-80.0 sensitivity 46.9 30.8-63.6 specificity 87.5 75.3-94.1 positive predictive ratio 71.4 50.0-86.2 negative predictive ratio 71.2 58.6-81.2 positive likelihood ratio 3.8 1.6-8.6 negative likelihood ratio 0.6 0.4-0.8 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 140 emergency (2014); 2 (3): 138-140 5. llovet jm, bartolí r, march f, et al. translocated intenstinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. j hepatol. 1998;28 (2): 307-13. 6. wiest r, garcia‐tsao g. bacterial translocation (bt) in cirrhosis. hepatology. 2005;41(3):422-33. 7. terg r, cobas s, fassio e, et al. oral ciprofloxacin after a short course of intravenous ciprofloxacin in the treatment of spontaneous bacterial peritonitis: results of a multicenter, randomized study. j hepatol. 2000;33(4):564-9. 8. singh n, wagener m, gayowski t. changing epidemiology and predictors of mortality in patients with spontaneous bacterial peritonitis at a liver transplant unit†. clin microbiol infect. 2003;9(6):531-7. 9. park mk, lee jh, byun yh, et al. changes in the profiles of causative agents and antibiotic resistance rate for spontaneous bacterial peritonitis: an analysis of cultured microorganisms in recent 12 years. korean j hepatol. 2007;13 (3):370-7. 10. heidari k, amiri m, kariman h, bassiri m, alimohammadi h, hatamabadi hr. differentiation of exudate from transudate ascites based on the dipstick values of protein, glucose, and ph. am j emerg med. 2013;31(5):779-82. 11. chinnock b, w hendey g. can clear ascitic fluid appearance rule out spontaneous bacterial peritonitis? am j emerg med. 2007;25(8):934-7. 12. evans lt, kim w, poterucha jj, kamath ps. spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites. hepatology. 2003;37(4):897-901. 13. castellote j, girbau a, maisterra s, charhi n, ballester r, xiol x. spontaneous bacterial peritonitis and bacterascites prevalence in asymptomatic cirrhotic outpatients undergoing large‐volume paracentesis. j gastroenterol hepatol. 2008;23 (2):256-9. 14. romney r, mathurin p, ganne-carrié n, et al. usefulness of routine analysis of ascitic fluid at the time of therapeutic paracentesis in asymptomatic outpatients: results of a multicenter prospective study. gastroenterol clin biol. 2005; 29(3):275-9. 15. chinnock b, afarian h, minnigan h, butler j, hendey gw. physician clinical impression does not rule out spontaneous bacterial peritonitis in patients undergoing emergency department paracentesis. ann emerg med. 2008;52(3):26873. 16. chinnock b, hendey gw, minnigan h, butler j, afarian h. clinical impression and ascites appearance do not rule out bacterial peritonitis. j emerg med. 2013;44(5):903-9. archives of academic emergency medicine. 2022; 10(1): e61 ca s e re p o rt jejunal dieulafoy’s lesion as a rare cause of massive gastrointestinal bleeding; a case report and literature review mohammad ebrahim kalantari1, newsha sardarzadeh1, ali mirsadeghi2, ali akbar bagherzadeh3, tooraj zandbaf2∗ 1. surgical oncology research center, mashhad university of medical sciences, mashhad, iran. 2. department of general surgery, faculty of medicine, mashhad medical sciences, islamic azad university, mashhad, iran. 3. innovative medical research center, faculty of medicine, mashhad medical sciences, islamic azad university, mashhad, iran. received: may 2022; accepted: june 2022; published online: 27 july 2022 abstract: jejunal dieulafoy’s lesion is difficult to diagnose due to its rarity, intermittent hemorrhage, and lesion site, which is largely inaccessible to conventional endoscopes. a 39-year-old man, who had no underlying disease, presented to the emergency department (ed) with weakness, dizziness, and dry cough with a history of several rectal bleeding episodes in the last few years. endoscopy was normal, and the colon was full of clots on colonoscopy, and no gross pathology was found. on computed tomography (ct) angiography, a hyperdensity was seen in the middle of the jejunum, possibly suggesting contrast extravasation. due to decreased hemoglobin of the patient, and hemodynamic instability, the patient became a candidate for surgery. a palpable lesion in the jejunum was touched that opened longitudinally, which revealed active arterial bleeding from the nipple-like lesion. this segment was resected, and an anastomosis was performed. histopathological examination of the small intestine confirmed a dieulafoy’s lesion. it seems that, when upper endoscopy and colonoscopy fail to identify the cause of gastrointestinal bleeding, a dieulafoy’s lesion should be included in the differential diagnoses. keywords: dieulafoy’s lesion; jejunal diseases; intestine, small; gastrointestinal hemorrhage; jejunum cite this article as: kalantari me, sardarzadeh n, mirsadeghi a, bagherzadeh aa, zandbaf t. jejunal dieulafoy’s lesion as a rare cause of massive gastrointestinal bleeding; a case report and literature review. arch acad emerg med. 2022; 10(1): e61. https://doi.org/10.22037/aaem.v10i1.1623. 1. introduction dieulafoy’s lesion (dl) was first described as "miliary aneurysms of the stomach" by dr. m. t. gallard in 1884 (1). in 1898, the french surgeon paul georges dieulafoy gave a more detailed description of this clinical condition, calling it an "exulceratio simplex"(2). in 1944, levine and valk were the first to describe a jejunal aneurysm with a submucosal artery rupture (3). the jejunum is where 1% of all confirmed cases of dl are identified (4). jejunal dl is difficult to diagnose due to its rarity, intermittent hemorrhage, and lesion site, which ∗corresponding author: tooraj zandbaf; faculty of medicine, bazarche sarab, imam khomeini 14, mashhad, iran. tooraj.zandbaf@gmail.com, https://orcid.org/0000-0002-4882-5058, tel:+98-9155114523; +98-5132250041, fax number: +98-513-2250048, orcid: https://orcid.org/00000003-2840-056x. is largely inaccessible to conventional endoscopes (5). with a male-to-female ratio of 1.2:1, jejunal dl has a little male predominance, with ages ranging from 10 to 95 years (55 ± 24 years; median, 82 years). the majority of individuals were diagnosed between the ages of 70 and 80. most instances were found in developed countries. several patients were on anticoagulants and/or nonsteroidal antiinflammatory drugs due to their older age and underlying chronic medical issues (6). dl is a rare and uncommon cause of massive gastrointestinal (gi) bleeding, and therefore, we would like to present our clinical experience with this unusual case to get more familiar with its various facets. our work has been documented according to the care guidelines. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem me. kalantari et al. 2 2. case presentation the patient was a 39-year-old man who presented to the emergency department (ed) with rectal bleeding, weakness, dizziness, and dry cough. the patient had a history of several rectal bleeding episodes in the last few years, as well as oral opium consumption. no history of underlying diseases was reported. an upper endoscopy had been performed a year ago, in which no lesions were seen. the patient was referred to our center from another hospital, where he had received 4 packed cells due to rectal bleeding. an initial evaluation in the ed revealed a normal temperature of 37.3°c, blood pressure of 90/60 mmhg, heart rate of 110 beats per minute, respiratory rate of 28 breaths per minute, and normal oxygen saturation of 96% in room air. lung examination was not remarkable. on abdominal examination, there was a slight generalized tenderness. the blood test results of the patient are presented in table 1. we think the cause of the patient’s thrombocytopenia was previous transfusion of packed cells. sputum polymerase chain reaction (pcr) for sars-cov-2 infection was positive. the patient was admitted in covid-19 ward and was resuscitated using intravenous crystalloids and four units of packed cells after a central venous (cv ) line was inserted. a chest x-ray was taken from the patient, which indicated homogeneous opacity in the lower zone of both lungs (figure 1a). the internist visited the patient and asked for a consultation with a general surgeon due to the lack of severe pulmonary problems as well as the significant rectal bleeding. consultation was performed with a general surgeon, and computed tomography (ct) angiography and gastroenterologist consultation were requested. endoscopy was normal and on colonoscopy, the colon was full of clots, which made it impossible to examine the colon closely. at this time, ct angiography was performed. hyperdensity was seen in the middle of the jejunum loops, possibly suggesting contrast extravasation. a small volume of free fluid was seen in the abdominal and pelvic cavities (figure 1b). at this time, the patient began to decompensate, and the patient’s hemoglobin decreased, resulting in need for additional packed cells and surgery. after laparotomy and during abdominal exploration, a palpable lesion in the small intestine was touched in 90 cm of ligament treitz. at the site of the lesion, the small intestine opened longitudinally, which revealed active arterial bleeding from the nipple-like lesion. this segment of the small intestine was resected, and an anastomosis was performed. no other pathology was found in the abdomen. the patient was transferred to the intensive care unit (icu). the patient’s gastrointestinal bleeding was stopped, and hemodynamics stabilized. after establishing bowel habits, the liquid diet was started, and finally, the patient was distable 1: the laboratory findings of the patient blood test result normal range white blood cells (x103 /µl) 17.3 4-10 hemoglobin (g/dl) 5.3 13.3-17.2 hematocrit (%) 16 38.9-50.9 platelets (x103 /µl) 58 150-450 esr1(mm/h) 3 <20 crp2 (mg/l) 16.8 up to 5.0 blood sugar(mg/dl) 112 75-100 sodium(meq/l) 130 136-146 potassium(meq/l) 6.3 3.5-5.5 d-dimer (ng/feu ml) 946 <500 blood urea nitrogen(mg/dl) 59 10-50 creatinine(mg/dl) 1.5 0.7-1.4 alanine aminotransferase (iu/l) 73 up to 41 aspartate aminotransferase (iu/l) 88 up to 37 amylase (iu/l) 443 0.00-86.00 prothrombin time (seconds) 17.3 10.5-14 partial thromboplastin time (seconds) 28 10-40 inr3 1.6 1: erythrocyte sedimentation rate. 2: c-reactive protein. 3. international normalized ratio. charged in good general condition one week after surgery. histopathological examination of the small intestine confirmed a dl. 3. discussion jejunal dl is an unusual cause of gastrointestinal bleeding, which can be severe and fatal. dl is a vascular anomaly with a diameter of 1 to 3 mm, which is 10 times bigger than the size of a healthy submucosal artery (7). a tiny mucosal defect with no surrounding mucosal inflammation characterizes this condition. these abnormal arteries usually take a tortuous path and protrude (2-5 mm) through the mucosal defect, making them prone to slight mechanical damage (8). antiplatelet drugs and alcohol intake were found to be risk factors for dl formation in the upper gastrointestinal tract. the mean hemoglobin level in patients with jejunal dl was found to be 8.4 g/dl at the time of presentation. the quantity of blood units given out varied from two to nine. the possible presenting symptoms of dizziness/fatigue (11%) and iron-deficiency anemia can be explained by the decline in hemoglobin levels (10%) (6). jejunal dl remains difficult to diagnose. the intermittency of the bleeding and lack of access to the jejunum with a regular endoscope makes it difficult to detect using conventional endoscopy. endoscopic guidance in the narrow jejunal canal can also be challenging (9). in our patient, we faced diagnostic challenge and a variety of differential diagnoses were considered when endoscopy and colonoscopy failed to identify the source of gastrointestinal bleeding. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e61 table 2: posterior-anterior chest x-ray of the patient with homogeneous opacity in the lower zone of both lungs (a); computed tomography angiography of patient suggesting contrast extravasation (b). the diagnosis can be further complicated by the presence of ambiguous clinical symptoms that could be mistaken for peptic ulcer disease or gastrointestinal malignancies. as a result, the efficiency of traditional endoscopy in jejunal dl is debatable (6). in our patient, after conventional endoscopies failed to detect the origin of bleeding, small bowel tumor was the most likely differential diagnosis we assumed. mesenteric angiography can be useful in cases of unidentified cause of bleeding when hemodynamic instability is evident. the use of computed tomography angiography to detect extra-gastric culprit vessels is very important. ct angiography is a quick and simple method that can identify bleeding rates as low as 0.5 ml/minute (10). the most sensitive tool for diagnosing active gi bleeding is radionuclide studies, which may detect bleeding rates as low as 0.1 ml/minute (11). capsule endoscopy and push enteroscopy have also been tried, with mixed results, particularly in stable patients who had unremarkable initial endoscopies. single and double balloon enteroscopy are the best procedures with diagnostic yields of 96% and 98%, respectively. since they complement noninvasive procedures like capsule endoscopy, these device-assisted enteroscopies are more effective in identifying dl. they provide secure and efficient diagnostic and therapeutic access to the jejunum via deep direct endoscopic access. the clinical presentation and capsule endoscopy results are important in determining oral or anal approach (6,12). endoscopic therapy was initially used to treat 64% of patients. in 32% of cases, direct surgical therapy was used, while angiographic embolization was performed in 4% of cases. in most hemodynamically unstable individuals, surgical assessment is required. intraoperative enteroscopy can be used to help locate the bleeder during surgery (6). yehya et al. presented a 19-year-old guy with multiple episodes of hematemesis and hematochezia. after resuscitation, a ct angiography was performed, which revealed no areas of active extravasation. the results of emergency upper and lower endoscopy were unclear. a tagged red blood cell scan revealed active bleeding in the proximal jejunum. the patient began to decompensate, necessitating additional blood products and vasopressors. immediate operative intervention was accomplished and the bleeding dieulafoy’s lesion in the jejunum was discovered. intestinal resection and primary anastomosis were performed (11). saada et al. presented a 27-year-old man with acute abdomen, bloody diarrhea, and syncope. upper and lower endoscopies, as well as angiography, failed to reveal a bleeding location during the investigation. following that, a scintigraphy revealed increased radiotracer activity in the right abdomen, which was consistent with small intestinal bleeding. based on these findings, the patient underwent an emergency laparotomy, which revealed the bleeding location in the jejunum and allowed for surgical resection (13). unlike these two cases, our patient was in his fourth decade of life and his ct angiography showed contrast extravasation in the jejunum. similarly, our patient’s gastrointestinal bleeding was surgically controlled. an obscure gastrointestinal bleeding occurs when the cause of bleeding cannot be identified using upper endoscopy or colonoscopy, and a dl, among other conditions, should always be included in the differential diagnosis. before any surgical intervention, if the patient’s condition is stable and there is enough time, ct angiography or radionuclide scan probably help identify the source of the bleeding and assist the surgeon during the operation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem me. kalantari et al. 4 4. conclusion when upper endoscopy and colonoscopy fail to identify the cause of gastrointestinal bleeding, a dl should be included in the differential diagnosis. surgery for a dl is now uncommon due to significant developments in endoscopic methods. if endoscopy fails to locate the source of bleeding, further imaging can be performed. in urgent circumstances, where additional imaging is not possible owing to a lack of time or resources, appropriate excision of the lesion for complete remission of the disease process should be undertaken. 5. declarations 5.1. acknowledgments the authors would like to express their profound gratitude to medical personnel involved in the treatment of this patient in imam reza hospital. 5.2. informed consent the patient’s written consent was obtained for the publication of this case report. 5.3. conflict of interest none. 5.4. funding and supports none. 5.5. competing interests the authors declare that they have no competing interests. 5.6. authors’ contributions mek and ns performed the surgery and reviewed the literature, tz, am, and aab wrote the manuscript and reviewed the literature. all authors read and approved the final manuscript. references 1. gallard t. aneurysmes milliares de l’estomac, donnant lieu a des hematemeses mortelles. bull. mem. soc. med. hop. paris. 1884; 1:84-91. 2. dieulafoy g. exulceratio simplex. l’intervebtion chirurgicale dans les hematemeses foudroyantes consecutives a l’exulceration simple de l’estomac. bull de l’acad de med. 1898; 39:49-84. 3. levine j, valk ad. aneurysm with rupture of a submucosal artery in the jejunum: case report. american journal of clinical pathology. 1944 nov 1;14(11):586-9. 4. nojkov b, cappell ms. gastrointestinal bleeding from dieulafoy’s lesion: clinical presentation, endoscopic findings, and endoscopic therapy. world journal of gastrointestinal endoscopy. 2015 apr 16;7(4):295. 5. schmulewitz n, baillie j. dieulafoy lesions: a review of 6 years of experience at a tertiary referral center. the american journal of gastroenterology. 2001 jun 1;96(6):168894. 6. malik a, inayat f, goraya mh, almas t, ishtiaq r, malik s, tarar zi. jejunal dieulafoy’s lesion: a systematic review of evaluation, diagnosis, and management. journal of investigative medicine high impact case reports. 2021 jan; 9:2324709620987703. 7. wan muhaizan wm, julia mj, al amin d. calibre persistent submucosal artery of the jejunum: a rare cause of massive gastrointestinal bleeding. the malaysian journal of pathology. 2002 dec 1;24(2):113-6. 8. chaer ra, helton sw. dieulafoy’s disease. journal of the american college of surgeons. 2003 feb 1;196(2):290-6. 9. khan r, mahmad a, gobrial m, onwochei f, shah k. the diagnostic dilemma of dieulafoy’s lesion. gastroenterology research. 2015 aug;8(3-4):201. 10. kozan r, gülen m, yılmaz tu, leventoğlu s, yılmaz e. massive lower gastrointestinal bleeding from a jejunal dieulafoy lesion. turkish journal of surgery/ulusal cerrahi dergisi. 2014;30(4):225. 11. yehya m, mayovska o, flick a, moszczynski z. a jejunal dieulafoy lesion: rare case necessitating surgical intervention. international journal of surgery case reports. 2020 jan 1; 72:541-5. 12. schneider m, höllerich j, beyna t. device-assisted enteroscopy: a review of available techniques and upcoming new technologies. world journal of gastroenterology. 2019 jul 7;25(27):3538. 13. saada m, perek s, agbaria m, raz-pasteur a. massive gastrointestinal bleeding from a jejunal dieulafoy lesion: an extraordinary presentation. case reports in gastroenterology. 2019;13(3):508-13. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2017; 5 (1): e18 or i g i n a l re s e a rc h screening characteristics of timi score in predicting acute coronary syndrome outcome; a diagnostic accuracy study mostafa alavi-moghaddam1, saeed safari2, hamideh alavi-moghaddam1∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: jun 2016; accepted: july 2016; published online: 9 january 2017 abstract: introduction: in cases with potential diagnosis of ischemic chest pain, screening high risk patients for adverse outcomes would be very helpful. the present study was designed aiming to determine the diagnostic accuracy of thrombolysis in myocardial infarction (timi) score in patients with potential diagnosis of ischemic chest pain. methods: this diagnostic accuracy study was designed to evaluate the screening performance characteristics of timi score in predicting 30-day outcomes of mortality, myocardial infarction (mi), and need for revascularization in patients presenting to ed with complaint of typical chest pain and diagnosis of unstable angina or non-st elevation mi. results: 901 patients with the mean age of 58.17 ± 15.00 years (19-90) were studied (52.9% male). mean timi score of the studied patients was 0.97 ± 0.93 (0-5) and the highest frequency of the score belonged to 0 to 2 with 37.2%, 35.3%, and 21.4%, respectively. in total, 170 (18.8%) patients experienced the outcomes evaluated in this study. total sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of timi score were 20 (95% ci: 17 24), 99 (95% ci: 97 100), 98 (95% ci: 93 100), 42 (95% ci: 39 46), 58 (95% ci: 14 229), and 1.3 (95% ci: 1.2 1.4), respectively. area under the roc curve of this system for prediction of 30-day mortality, mi, and need for revascularization were 0.51 (95% ci: 0.47 0.55), 0.58 (95% ci: 0.54 0.62) and 0.56 (95% ci: 0.52 0.60), respectively. conclusion: based on the findings of the present study, it seems that timi score has a high specificity in predicting 30-day adverse outcomes of mortality, mi, and need for revascularization following acute coronary syndrome. however, since its sensitivity, negative predictive value, and negative likelihood ratio are low, it cannot be used as a proper screening tool for ruling out low risk patients in ed. keywords: coronary artery disease; prognosis; myocardial infarction; decision support techniques; angina, unstable © copyright (2017) shahid beheshti university of medical sciences cite this article as: alavi-moghaddam m, safari s, alavi-moghaddam h, kariman h. screening characteristics of timi score in predicting acute coronary syndrome outcome; a diagnostic accuracy study. emergency. 2017; 5 (1): e18. 1. introduction coronary artery disease (cad) is a major health problem worldwide (1). although during the past decades, with development of preventive measures and improvement of diagnostic and therapeutic approaches, cad related deaths have decreased by more than 40%, cad still remains the largest killer of the us population (2, 3). about half of all deaths in developed countries and 25% of those in developing ones oc∗corresponding author: hamideh alavi-moghaddam; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989122030036, email: hamide_mogaddam@yahoo.com cur due to cad (4). it is predicted that until 2020, the number of cad related deaths will exceed that of infectious diseases (5). it seems that rapid diagnosis, and choosing the best treatment in the initial stages are of great importance in improving the outcome of cad patients. in cases that electrocardiogram (ecg), as the most available and rapid diagnostic tool, is not helpful in decision making (cases of unstable angina and non-st elevation mi), screening high risk patients for adverse outcomes would be very helpful. various clinical decision rules and scoring systems have been developed for this purpose (6, 7). an ideal model in this regard, should have high sensitivity and be able to predict the outcome accurately, using readily available clinical information. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. alavi-moghaddam et al. 2 one of these systems is thrombolysis in myocardial infarction (timi) scoring model that helps divide the patients into 2 groups of low risk (score 0-1) and high risk (score > 1) regarding adverse 30-day outcome. a study on 279 patients visiting ed showed that timi score is a valid tool for assessing 30-day mortality risk (8). additionally, in a study on 3609 stelevation mi patients, it was concluded that timi score has both short and long term value in predicting patient mortality in those that underwent primary percutaneous coronary intervention (9). a study by lee et al. in 2011 in pennsylvania also revealed the good ability of this system in predicting the incidence of 30-day cardiovascular adverse events following typical chest pain (10). currently, in many developing countries, supplementary diagnostic measures, such as exercise testing or echocardiography, is not available and cannot be done in eds. in this situation, using clinical scoring systems may be helpful in patient disposition. therefore, the present study was designed aiming to determine the diagnostic accuracy of timi score in predicting 30-day outcome of patients presenting to ed with diagnosis of unstable angina or nonst elevation mi. 2. methods 2.1. study design this study was designed to evaluate the diagnostic accuracy of timi clinical scoring system in prediction of 30-day outcome of patients presenting to ed of imam hossein hospital, tehran, iran, with potential diagnosis of ischemic chest pain, during a 6-month period (from october 2015 to march 2016). the study was approved by the ethics committee of shahid beheshti university of medical sciences and the researchers adhered to the principles of helsinki declaration and patient data confidentiality throughout the study. a written informed consent was obtained from all the patients for participating in the study. 2.2. participants all the patients with chest pain who were diagnosed with unstable angina or non-st elevation mi were entered to the study without any age or sex limitation, using census sampling. patients with unstable hemodynamics, evidence of st segment elevation in the initial ecg and those who did not give consent for participating were excluded. patients with diagnosis of st elevation mi were immediately scheduled for receiving thrombolytic therapy or percutaneous coronary intervention (pci). 2.3. data collection after learning the study aims and method, the in charge emergency medicine residents were held responsible for data gathering and filling the checklist for the patients on admission. all the patients were relocated to cardiac monitoring unit, and initial life support measures (pain relief with serum nitroglycerin and intravenous morphine, o2 therapy, blood pressure monitoring and . . . ) were initiated on admission to ed. in addition, ecg and cardiac enzymes were ordered. all patients underwent 12 lead ecg and in cases suspected to inferior or posterior wall mi, posterior/inferior leads were added. if the pain was not relieved within 20 30 minutes after admission, despite initiating therapy with nitroglycerin and intravenous morphine, ecg was repeated with 20 -30 minute intervals up to 3 times. ecg interpretations were done by emergency medicine residents and approved by the in charge attend of the shift and on call internists. based on the treatment protocol of the studied health center, evaluation of cardiac enzymes including creatine kinase (ck), ckmb, and troponin was also ordered for all the patients on admission and 6 hours later. if the final diagnosis was unstable angina or non-st elevation mi, all the baseline characteristics of the patient including age and sex, pain characteristics, status of the known risk factors of arteriosclerosis (hypertension, diabetes, smoking, overweight, hyperlipidemia and . . . ), history of cardiovascular diseases (stroke, mi, and . . . ), drugs history, ecg findings, laboratory findings especially level of cardiac enzymes as well as variables needed for calculating timi score were gathered by the in charge resident, using a checklist prepared for this purpose. required data regarding the final outcome of the patients were gathered from their clinical files or, if not available, by phone call with the patient, their relatives, or their cardiologist by a senior emergency medicine resident. considering the definition of timi score the evaluated outcomes including mi, need for revascularization and all-cause mortality during the 30 days after admission to ed (11). 2.4. statistical analysis all analyses were done using spss version 20 and stata 11. mean, standard deviation, median, range, frequency, and percentage were used to describe data. to calculate the diagnostic accuracy of timi system, sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio, and area under the receiver operating characteristic (roc) curve were calculated. 3. results: 3.1. baseline characteristics of the patients 901 patients with the mean age of 58.17 ± 15.00 years (1990) were studied (52.9% male). table 1 shows the baseline characteristic of the patients. the most common accompanying diseases included hypertension (51.4%) and diabetes (19.8%). st segment changes (39.2%) and t wave inversion (31.6%) were the most common early ecg findings, rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e18 table 1: baseline characteristics of the studied patients variable number (%) sex female 424 (47.1) male 477 (42.9) risk factors hypertension (51.4) 463 diabetes 178 (19.8) smoking 88 (9.8) positive family history 29 (3.2) hyperlipidemia 88 (9.8) number of accompanying risk factors 0 289 (32.1) 1 414 (45.9) 2 164 (18.2) 3 32 (3.6) 4 2 (0.2) history of cardiac failure 26 (2.9) ptca history 58 (6.4) ecg findings st deviation 353 (39.2) t inversion 285 (31.6) left bundle branch block 28 (3.1) right bundle branch block 3 (0.3) atrial fibrillation 17 (1.2) sinus tachycardia 8 (0.9) ventricular tachycardia 1 (0.1) multifocal atrial tachycardia 1 (0.1) paroxysmal supraventricular tachycardia 6 (0.7) ptca: percutaneous transluminal coronary angioplasty; ecg: electrocardiography. table 2: frequency of timi risk factors among studied patients (n = 901) item number (%) age ≥ 65 321 (35.6) ≥ 3 cad risk factors 34 (3.8) known cad (stenosis ≥ 50%) 12 (1.3) asa use in past 7 days 59 (6.5) sever angina (≥ 2 episodes / 24 hours) 3 (0.3) st segment changes ≥ 0.5 mm 353 (39.2) positive cardiac marker 95 (10.5) cad: coronary artery disease; asa: acetylsalicylic acid. table 3: 30-day outcomes of studied patients outcome number (%) myocardial infarction 88 (9.8) urgent revascularization 75 (8.3) coronary angiography 488 (54.2) percutaneous coronary intervention (pci) 332 (36.8) coronary artery bypass graft (cabg) 34 (3.8) admission to coronary care unit (ccu) 712 (79.0) death 7 (0.8) spectively. table 2 depicts the frequency of factors used in timi clinical scoring system among the studied patients. the most common factors in this regard were more than 0.5 mm changes in st segment (39.2%) and age ≥ 65 years (35.6%). mean timi score of the studied patients was 0.97 ± 0.93 (0-5) and the highest frequency of the score belonged to 0 to 2 with 37.2%, 35.3%, and 21.4%, respectively. table 3 reveals the final outcome of the participants. 488 (54.2%) of the patients underwent angiography of coronary arteries, based on which 22 (2.4%) had severe obstruction, 371 (41.2%) had moderate obstruction, 72 (8.0%) had mild and 23 (2.6%) had nonsignificant obstruction. 3.2. characteristics of timi screening system in total, 170 (18.8%) patients experienced the outcomes evaluated in this study. total sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of timi score were 20 (95% ci: 17 24), 99 (95% ci: 97 100), 98 (95% ci: 93 100), 42 (95% ci: 39 46), 58 (95% ci: 14 229), and 1.3 (95% ci: 1.2 1.4), respectively. table 4 shows the screening characteristics of timi score for predicting 30-day mortality, need for revascularization, and mi. the findings reveal the high specificity and low sensitivity of this system in these regards. area under the roc curve of this system for prediction of 30-day mortality, mi, and need for revascularization were 0.51 (95% ci: 0.47 0.55), 0.58 (95% ci: 0.54 0.62) and 0.56 (95% ci: 0.52 0.60), respectively. 4. discussion: findings of the present study, reveal the high specificity (99%) of timi score in prediction of 30-day clinical outcomes of mortality, mi, and need for revascularization. however, it has a low sensitivity (1.2 15%) and its screening power is low. a study by marcoon et al. in 2013 in america showed that the probability of adverse 30-day outcome in patients with typical chest pain and 0 timi score is lower than 1% (12). in addition, a cohort study by pollack et al. revealed that the risk of short term adverse outcome is 2.1% in patients with 0 timi score and 100% in those with a score higher than 7 (13). in a meta-analysis, hess et al. expressed that there is 1.8% risk of 30-day cardiac events in those with 0 timi score, while the risk is 4% for those with a score of 1. they found a strong linear correlation between timi score and incidence of cardiac events (14). in a cohort study in 30, lee et al. concluded that patients with high risk of adverse outcome may be identified in ed using this system (10). this result is completely in line with the findings of the present study since the high specificity of this model makes it a useful tool to rule in at risk patients. on the other hand, low sensitivity, negative prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. alavi-moghaddam et al. 4 table 4: screening performance characteristics of timi score in 30-day outcome prediction of patients with unstable angina/non-st elevation myocardial infarction (mi) outcomes mortality mi revascularization sensitivity 1.2 (0.5-2.6) 15 (12-18) 13 (10-16) specificity 100 (98-100) 100 (98-100) 99 (97-99) positive predictive value 100 (56-100) 100 (94-100) 97 (89-99) negative predictive value 38 (35-42) 41 (37-44) 40 (36-43) positive likelihood ratio ∞ ∞ 37 (9-143) negative likelihood ratio 1.5 (1.4-1.6) 1.4 (1.3-1.5) 1.5 (1.4-1.6) data were presented with 95% confidence interval. dictive value and negative likelihood ratio has limited its use for screening and ruling out high risk patients in ed. however, this tool can be at least used for preventing discharge of high risk patients from ed. in the meta-analysis by hess et al. that included 8 studies, at >0 cut off, sensitivity was calculated to be 97.2%, specificity was 25.0%, and negative likelihood ratio was 0.11. they concluded that patients should not be discharged solely because of low timi score (14). the findings of the preset study also showed the low sensitivity (20%) and high specificity (99%) of timi score. jain et al. compared the prognostic value of timi score with heart score in predicting 30-day and 5-year outcomes of mortality, mi, and revascularization, and concluded that heart score is superior (19). this finding was in line with other studies that expressed heart score has higher discriminatory power compared to timi score (20, 21). it has also been found that global registry of acute coronary events (grace) risk score has significantly higher discriminatory accuracy in comparison with timi score (22). in comparison of heart, timi, and grace scores, heart score is found to be the best of the 3 (23). a study compared emergency department assessment of chest pain score (edacs), with heart and timi scores in prediction of 6-week major adverse cardiovascular events of mi, revascularization and death, in a 6 week follow-up period for patients with chest pain presenting to ed. it was revealed that edacs score was able to identify more low-risk patients compared to the other 2 scores (24). modified goldman risk score in combination with high-sensitivity troponin was also found to identify significantly more low-risk patients for 30-day adverse outcomes compared to timi score (25). chads2 score has also been deemed more practical for outcome prediction of acute mi patients (26). some studies even expressed that timi score does not have a predictive capacity, since its area under the roc curve is 0.532, which is close to the area under the curve found in this study (27). among the limitations of this study is extraction of outcome from patients’ medical profile might leading to miss some important points, however, we tried to minimize this probability by contacting the patient or their in-charge cardiologist. 5. conclusion: based on the findings of the present study, it seems that timi score has a high specificity in predicting 30-day adverse outcomes of mortality, mi, and need for revascularization following acute coronary syndrome. however, since its sensitivity, negative predictive value, and negative likelihood ratio are low, it cannot be used as a proper screening tool for ruling out low risk patients in ed. 6. appendix 6.1. acknowledgements this article has been derived from dr. hamideh alavimoghaddam student thesis to receive his specialist degree in emergency medicine from shahid beheshti university of medical sciences. authors would like to acknowledge all the emergency department staff of imam hossein and shohadaye tajrish hospitals. 6.2. authors contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the 4 criteria of authorship recommended by the international committee of medical journal editors. 6.3. conflict of interest none. 6.4. funding none. references 1. hata j, kiyohara y. epidemiology of stroke and coronary artery disease in asia. circulation journal. 2013;77(8):1923-32. 2. thom t, haase n, rosamond w, et al. heart disease and stroke statistics–2006 update: a report from the american heart association statistics committee and stroke statistics subcommittee. circulation. 2006;113(6):e85. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e18 3. ford es, ajani ua, croft jb, et al. explaining the decrease in us deaths from coronary disease, 1980-2000. new england journal of medicine. 2007;356(23):2388-98. 4. beaglehole r. international trends in coronary heart disease mortality and incidence rates. european journal of cardiovascular risk. 1999;6(2):63-8. 5. huffman md, lloyd-jones dm, ning h, et al. quantifying options for reducing coronary heart disease mortality by 2020clinical perspective. circulation. 2013;127(25):2477-84. 6. montalescot g, sechtem u, achenbach s, et al. 2013 esc guidelines on the management of stable coronary artery disease. european heart journal. 2013;34(38):2949-3003. 7. roffi m, patrono c, collet j-p, et al. 2015 esc guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation. european heart journal. 2015:ehv320. 8. ehsan ma, mahmood m, siddique ma, et al. prediction of major adverse cardiac events of patients with acute coronary syndrome by using timi risk score. university heart journal. 2013;8(2):73-9. 9. damman p, woudstra p, kuijt wj, et al. shortâăřand longâăřterm prognostic value of the timi risk score after primary percutaneous coronary intervention for stâăřsegment elevation myocardial infarction. journal of interventional cardiology. 2013;26(1):8-13. 10. lee b, chang am, matsuura ac, marcoon s, hollander je. comparison of cardiac risk scores in ed patients with potential acute coronary syndrome. critical pathways in cardiology. 2011;10(2):64-8. 11. antman em, cohen m, bernink pj, et al. the timi risk score for unstable angina/non-st elevation mi: a method for prognostication and therapeutic decision making. jama. 2000;284(7):835-42. 12. marcoon s, chang am, lee b, salhi r, hollander je. heart score to further risk stratify patients with low timi scores. critical pathways in cardiology. 2013;12(1):1-5. 13. pollack cv, sites fd, shofer fs, sease kl, hollander je. application of the timi risk score for unstable angina and nonâăřst elevation acute coronary syndrome to an unselected emergency department chest pain population. academic emergency medicine. 2006;13(1):13-8. 14. hess ep, agarwal d, chandra s, et al. diagnostic accuracy of the timi risk score in patients with chest pain in the emergency department: a meta-analysis. canadian medical association journal. 2010;182(10):1039-44. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e32 rev i ew art i c l e accuracy of triage systems in disasters and mass casualty incidents; a systematic review jafar bazyar1,2,3, mehrdad farrokhi1, amir salari4, hamid safarpour2,5, hamid reza khankeh1∗ 1. health in emergency and disaster research center, university of social welfare and rehabilitation sciences, tehran, iran. 2. department of nursing, school of nursing and midwifery, ilam university of medical sciences, ilam, iran. 3. pre-hospital medical emergency organization, ilam university of medical sciences, ilam, iran. 4. department of health in emergencies and disasters, school of public health, tehran university of medical sciences, tehran, iran. 5. non-communicable diseases research center, ilam university of medical sciences, ilam, iran. received: january 2021; accepted: march 2021; published online: 30 april 2022 abstract: introduction: to prioritize patients to provide them with proper services and also manage the scarce resources in emergencies, the use of triage systems seems to be essential. the aim of this study was to evaluate the accuracy of the existing triage systems in disasters and mass casualty incidents. methods: the present study is a systematic review of the accuracy of all triage systems worldwide. the results of this study were based on the articles published in english language journals. in this research, all papers published from the beginning of 2000 to the end of 2021 were sought through different databases. finally, a total of 13 articles was ultimately selected from 89 articles. results: 13 studies on the accuracy of triage systems were reviewed. the start, mstart, salt, smart, care flight, asav, mptt, sieve and esi triage systems, had an accuracy, sensitivity, and specificity of less than 90%. only the smart triage system had an overall accuracy of more than 90%. conclusion: according to the findings of the current systematic review, the performance of the existing triage systems in terms of accuracy of prioritizing the injured people and other performance indexes is not desirable. therefore, to improve the performance and increase the precision of triage systems, the world nations are recommended to change or revise the indexes used in triage models and also identify other influential factors affecting the accuracy of triage systems. keywords: disasters; data accuracy, triage; mass casualty incidents; systematic review cite this article as: bazyar j, farrokhi m, salari a, safarpour h, khankeh hr. accuracy of triage systems in disasters and mass casualty incidents; a systematic review. arch acad emerg med. 2022; 10(1): e32. https://doi.org/10.22037/aaem.v10i1.1526. 1. introduction triage, with a french origin (trier), means prioritizing and is used to classify patients and people affected by emergencies and disasters. this classification leads to better management of services and optimal use of the available resources for injured people and patients (1). a triage system is considered optimal, when it can identify patients and injured individuals who need immediate care and provide access to rapid diagnostic and therapeutic measures (2, 3). if the triage system does not function properly and categorizes patients appro∗corresponding author: hamid reza khankeh; health in emergency and disaster research center, university of social welfare and rehabilitation sciences, tehran, iran. email: ha.khankeh@uswr.ac.ir, tel: +98 021 2218 0160, orcid: https://orcid.org/0000-0002-9532-5646. priately, it will cause waste of resources, delay in the provision of services to patients according to their needs, dissatisfaction and adverse outcomes in patients, and in some cases, it may endanger the patient’s life (4). thus, the use of an efficient triage system with good reliability and validity seems to be essential when providing services to patients and injured individuals, which sometimes determines the survival of these people (5-7). the inhabitants of the world are annually faced with many natural and man-made hazards and emergencies, which have caused a lot of physical damage to these people (8). the use of the triage system for the people who have been injured because of emergencies and disasters that harm a large number of people is considered a necessary measure, through which appropriate health care and survival of the injured can be guaranteed (9-11). nowadays, to prioritize patients, different triage systems are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 2 applied based on the age group, the cause of damage, the geographical area, and other characteristics of the affected people (1). the most common of which are simple triage and rapid treatment (start), modified simple triage algorithm and rapid treatment (mstart), sort, assess, lifesaving interventions, treatment/transport (salt), smart, care flight, amberg-schwandorf algorithm for primary triage (asav ), modified physiological triage tool (mptt), sieve, and emergency severity index (esi) triage systems. these triage systems are increasingly being used to prioritize injured people in emergencies and disasters, as well as in health and medical systems; however, there is no single comprehensive system that is universally agreed upon. each country or region of the world uses a different system for triage based on its own needs (12-15). in general, there are many controversies in the world concerning the accuracy of the triage systems. therefore, to determine the proper functioning of these triage systems, their accuracy is evaluated using several divergent indicators encompassing sensitivity, specificity, positive and negative predictive value, overall accuracy, over-triage, and under-triage (16, 17). sensitivity and specificity indicate the correct classification of the affected people and the predictive value of the triage indicates the power of the triage method in correct classification of these individuals. over-triage categorizes injured individuals or patients in higher classes and under-triage in lower classes compared to their actual level of severity. in over-triage, the person is provided with a service that he/she does not need, resulting in waste of time and resources, on the contrary, in under-triage, the person is provided with services not meeting his actual needs, which can endanger the life of the individual (17, 18). various studies have been conducted to estimate the accuracy of different types of triage systems worldwide, but, to the best of our knowledge, there is no comprehensive study on the comparison of different types of triage methods. in other words, in the studies done, only two or three methods have been compared. consequently, the present study aims to assess and compare the accuracy of the indicators of the all triage systems through a systematic review. 2. method 2.1. study protocol and search strategy the present study is a systematic review of the accuracy of the all triage systems used worldwide. the results of this study were based on the articles published in english language journals. in this research, all papers published from the beginning of 2000 to the end of 2019 were sought through the medlib, scopus, web of science, pubmed, cochrane library, science direct, and google scholar databases. all articles with medical subject headings (mesh) and keywords including triage systems, sensitivity, specificity, predictive values, over-triage, under-triage, disaster, and mass casualty incidents (mcis) were searched; the keywords were used in isolation or in combination, using and/or: triage systems or disaster or mass casualty incidents and accuracy or sensitivity or specificity or predictive values or over triage or under triage. 2.2. screening and data extraction accordingly, all articles on triage systems were first collected and, upon completion of the search, a list of abstracts was prepared. after concealing the profile of the articles, such as the name of the author, the name of the magazine, etc., the full text of the articles was given to two qualified researchers to review the articles. each article was independently reviewed by two people. if the articles were rejected by the two reviewers, the reason was also mentioned by them and in case of disagreement between them, the article was judged by a third reviewer. data extraction was performed using a pre-prepared checklist that included the study location, study time, triage system, community under study, sensitivity, specificity, predictive value, over-triage, and undertriage. 2.3. quality assessment the quality of articles was assessed using the newcastle ottawa scale (nos) checklist. this checklist includes 8 items, each ranging from 0 to 1. the scores between 0 to 5, 6-7, and 8 represent low, medium, and high quality, respectively. the lowest acceptable score for entering the study was 5 (19). 2.4. inclusion and exclusion criteria articles meeting all the following criteria were included in the study: addressing triage systems; reporting one or all of following indexes including validity and reliability (sensitivity, specificity, positive and negative predictive values, overtriage, and under-triage); having high quality according to the nos checklist, and being published in english. interventional studies, conference proceedings, qualitative studies, and case reports, as well as studies not written in english were excluded. 2.5. study selection there were 89 papers on triage systems, out of which, 36 and 21 articles were excluded due to repetitiveness and irrelevance to the study, respectively. after reviewing the abstract of the articles, 19 additional papers lacking the required information were excluded from the study. finally, 13 articles, which met the inclusion criteria, were considered (diagram 1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e32 2.6. triage systems in results different studies have been done to evaluate the validity and reliability of the triage systems, with the aim to measure the accuracy of these systems in the evaluation of the injured people. typically, the basics of performing triage systems are similar. so, a triage system should be used, which could recognize and prioritize the injured people, take less time, and manage resources based on the patients’ needs. the accuracy of the triage systems, which is evaluated using sensitivity, specificity, positive and negative predictive value, as well as the amount of overand under-triage, both of which affect the efficient use of limited resources, can show the performance of the triage system in accurate prioritization of the patients and optimal use of the available resources. accordingly, the present study aims to probe the accuracy of nine world-class triage systems, including start, mstart, salt, smart, care flight, asav, mptt, sieve and esi. the characteristics of the reviewed articles are presented in table 1. 2.7. triage systems in the prehospital setting the start triage system: this is one of the most common triage systems in large events such as natural disasters, used for people over 8 years of age. the duration of this triage is about 30 to 60 seconds. in this method, people are classified with green (minor injury), yellow (delayed), red (immediate) and black (died) tags, and the indicators under investigation in this system are the ability to walk, breathing and its rate, capillary refill time, and the ability to follow commands (1, 17, 20). the mstart triage system: this triage system is a modulated type of the start triage system whose performance and indices are similar to start triage system. the only difference is that, in the mstart method, the capillary refill time index is replaced by no palpable pulse index (21). the salt triage system: similar to the start method, in this method, individuals are categorized using green, yellow, red, and black tags, but people are prioritized in a different way. in the salt method, people are firstly classified into three groups based on walking ability. then, based on the prioritization performed in the first stage, and with the aim of controlling life-threatening factors, the second step is to evaluate and take actions such as severe bleeding control, airway opening, chest compression, and antidote injection. finally, following the treatment and response of the injured people to the treatment, they will be prioritized using one of the tags mentioned above, and then treated and transmitted to medical centers (1, 5, 22-24). the smart triage system: this triage system, like other systems, has 4 tags and determines priorities based on walking, breathing, capillary refill time, and the ability to follow the commands (25). the care flight triage system: in the care flight triage method, people are assessed on the basis of walking ability, respiration, radial pulse, and the ability to follow the commands using 4 green (delayed), yellow (emergency), red (immediate) and black (unsalvageable) tags, with the difference that the criterion concerning “following commands” is checked before other criteria. this triage system is used to quickly target a large number of casualties and takes about 15 seconds to complete the triage (1). the asav triage system: this triage system is a new triage method. individuals, as in other triage methods, are classified via 4 tags including green (minor injury), yellow (delayed), red (immediate) and black (died). in this system, people are classified according to the severity of their bleeding, respiration, radial pulse, and the ability to follow commands (1, 26). the sieve triage system: this method is used for adults. in this method, people are prioritized using four colors: green, yellow, red, and black. the indicators investigated in this method are walking, respiration, and pulse rate (5). the mptt triage system: in this method, people are prioritized using 4 colors including green, yellow, red, and black. indicators examined in this method include the ability to walk, breath, pulse, and glasgow coma scale (gcs), indicating the level of consciousness of the person. 2.8. triage systems in hospital setting the 5-level triage system (esi) (emergency severity index): this is one of the most widely used triage systems, which is currently accepted by many countries around the world (26). although the esi is the most commonly used method for routine triage, this method is based both on acuity and resource needs, and could also theoretically be used in mci situations to prioritize patients for placement in the hospital (27). in this system, patients are classified into five levels based on the severity of illness or injury and the need for facilities. at levels 1 and 2, injured patients are prioritized based on the level of severity and at levels 3, 4 and 5, based on the need for emergency facilities. in this method, injured individuals have suffered the most harm at level 1, and the least injury at level 5 (20). 3. results 13 articles published between 2000 and 2021 in the field of triage systems around the world were included in this study, in which the accuracy of triage systems was investigated. in this study, the accuracy of triage systems has been assessed in terms of sensitivity, specificity, positive and negative predictive values, over-triage, under-triage, and overall accuracy. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 4 3.1. the accuracy of the start triage system in the study conducted by mary colleen bhalla et al. in the united states (2015) on 100 patients aged 17 to 92, who were traumatized by incidents and emergencies and evaluated using the start triage system, the accuracy of the start triage system was measured. in this study, after evaluating the patients, the sensitivity and specificity for accuracy of triage were 55% and 85%, and the level of over-triage and undertriage was 12% and 33%, respectively. furthermore, based on the prioritization and the tags assigned to the patients, sensitivity, specificity, and positive and negative predictive values were 80%, 55%, 72.4%, and 79.2% for the green color (minor injury), respectively. these indicators were 0%, 76.8%, 0%, and 93.6%, for the yellow color (delayed). they were also 13.8%, 93%, 44.4%, and 72.5%, and 50%, 100 %, 100%, and 96.9% for the red (immediate) and black colors (died), respectively (16). ca kahn et al. (2003) performed a study in california on 148 people injured in rail accidents. in that study, they used the start triage system to prioritize the injured patients. they have reported that the degree of sensitivity and specificity of triage has been equally 90%, and the prioritizing accuracy of the injured patients has been 44.6%. in addition, 79 (53%) and 3 (2%) cases were subjected to over-triage and undertriage, respectively. in this study, based on the priority assigned to the injured people, sensitivity, specificity, positive and negative predictive value were 45.8%, 89.3%, 94.8%, and 27.8%for the green priority 39.1% , 11.9%, 13.2%, and 36.4% for the yellow priority and 100%, 77.3%, 9.1%, and 100% for the red priority (17). in another study conducted by alan garner et al. in australia on 1144 injured people, who were injured due to various causes, including road-traffic accident, industrial, sports, burn, etc. incidents, the start triage system was used to prioritize patients and its accuracy was evaluated. accordingly, the sensitivity of this method was 85% and the specificity level was 86% (21). in a study conducted by wallis et al. (2006), sensitivity and specificity were estimated to be 39.2% and 78.7%, respectively. in a study conducted by mckee et al. (2019) on 125 subjects, correct triage rate was 36%, over-triage 7.2% and under-triage 56.8% (28). in the study conducted by france et al., who aimed to assess the diagnostic accuracy of the start algorithm for disaster triage, the results showed that proportion of patients correctly triaged using start ranged from 0.27 to 0.99 with an overall triage accuracy of 0.73 (95% ci, 0.67 to 0.78). proportion of over-triage was 0.14 (95% ci, 0.11 to 0.17) while the proportion of under-triage was 0.10 (95% ci, 0.072 to 0.14)(29). 3.2. the accuracy of the mstart triage system in a study conducted by garner et al. in australia (2001) on 1144 people, who were injured due to traffic, industrial, sports, burn, etc. incidents, which addressed the accuracy of the mstart triage system, the sensitivity and specificity of the system were estimated to be 84% and 91%, respectively(21). in another study, philipp wolf et al. in germany (2014) used the mstart triage system to prioritize 780 injured patients and assessed the validity and reliability of this method. the sensitivity and specificity of this method were 88.2% and 93.9%, respectively. moreover, the accuracy of the prioritization of the patients was 84.8% and over-triage and under-triage levels were 3.8% and 6.8%, respectively. it is worth mentioning that the mean duration of the triage was 41 sec in each patient (26). 3.3. the accuracy of the salt triage system mary colleen bhalla et al., in a study conducted in the united states (2015), on 100 patients, who were traumatized by accidents and emergencies and evaluated using salt triage system, estimated the sensitivity and specificity of the salt triage system to be 65% and 88.3%, respectively. in this study, over-triage and under-triage were 5% and 30%, respectively. moreover, based on the prioritization of the patients, sensitivity, specificity, and positive and negative predictive values were 91.7%, 47.5%, 72.4%, and 79.2% for the green color (minor injuries), 20%, 93%, 54.5%, and 74.2% for the yellow color (delayed), 7.20%, 93%, 54.5%, and 74.2% for the red color (immediate), and 50%, 100%, 100%, and 9.96% for the black color (died), respectively(16). in another study performed by cone dc in the united states (2011) on 547 injured people, who were injured in highway traffic accidents, the salt triage system was used to prioritize the injured patients. in this study, the overall accuracy of triage of the injured people was equal to 70%. over-triage and under-triage were also 6.8% and 23.2%, respectively (25). in a scenario study in alabama, jones et al. (2014) investigated the accuracy of salt triage system. the accuracy, over-triage, and under-triage were estimated to be 66%, 22%, and 10%, respectively. in a study conducted by mckee et al. (2019) on 125 subjects, correct triage rate was 52%, overtriage 21.6%, and under-triage was 26.4% (28). 3.4. the accuracy of the smart triage system in a study done by cone dc et al. (2011) in the united states, which investigated the accuracy of the smart triage system on 544 highway accident victims, the overall accuracy of the prioritization of the system was 93%. over-triage and undertriage rates were 1.8% and 5.1%, respectively (25). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e32 3.5. the accuracy of the care flight triage system garner et al., in a study conducted in australia (2001), used the care flight triage system to prioritize 1144 individuals injured by traffic, industrial, sports, burn, etc. incidents. subsequently, the validity and reliability of this triage system were evaluated. accordingly, the sensitivity and specificity of this method were 82% and 96%, respectively (21). in their study, wallis and carley, estimated the accuracy and specificity of care flight triage system %98.9 and %39.2, respectively. in a study conducted by mckee et al (2019) on 125 subjects, correct triage rate was 36%, over-triage 5.6%, and under-triage was 57.6% (28). 3.6. the accuracy of the asav triage system in a study performed by philipp wolf et al. in germany (2014), which prioritized 780 injured victims using the asav triage system, and assessed the validity and reliability of the system, the sensitivity and specificity of the system were 87.4% and 91%, respectively. furthermore, the overall accuracy of the prioritization of casualties was 83.9%. the overtriage and under-triage rates were 4.6%, and 9.7%, respectively. in this method, the average time required for the triage of each injured person was 35.4 seconds (26). 3.7. the accuracy of the mptt triage system in a study done by james vassallo et al., in england (2017), on 5654 injured people over 18 years of age, the mptt triage system was used to prioritize the injured participants and the accuracy of the triage system was evaluated. the sensitivity and specificity levels of the mptt triage system were 69.9% and 65.3%, respectively (30). 3.8. the accuracy of the sieve triage system in a study conducted by alan garner et al. in australia (2001), which investigated the accuracy of the sieve triage system, the sensitivity and specificity of this triage system were estimated to be 45% and 88%, respectively. in this study, the use of capillary refill time or heart rate index for determining the index of pulse rate and prioritization of the casualties was also investigated. results revealed that there was no significant difference between sensitivity and specificity levels, when the two methods were examined. particularly, when capillary refill time index was used, the sensitivity and specificity were 45% and 89%, respectively. they were 45% and 88%, respectively, when the heart rate index was taken into consideration (21). in a study conducted by mckee et al. (2019) on 125 subjects, correct triage rate was 36.8%, overtriage 6.4%, and under-triage 57.6% (28). 3.9. the accuracy of the 5-level triage system, or esi the validity and reliability of the esi triage system was investigated in a study conducted by kariman et al. in iran (2011) on 1050 patients. in this study, the sensitivity and specificity of the prioritization of the patients were 100% and 99.8% at level 1, 53.2% and 97.5% at level 2, 90.7% and 93.7% at level 3, 67.1% and 98.3% at level 4, and 98% and 94% at level 5, respectively (20). in another study done by buschhorn bh et al. in the united states (2013) on 150 patients, the validity and reliability of the esi triage system were evaluated. in this study, sensitivity, specificity, and the overall accuracy of prioritizing the patients were 0%, 97.3%, and 94.7% at level one, 57.1%, 84.9%, and 69.3% at level two, 67.9%, 68.1%, and 68% at level 3, and 33.3%, 93.1% and 90.1% at level 4, respectively. at level 5, only specificity value was estimated, which was equal to 96% (31). in a study conducted by platts-mills tf et al. in carolina (2010), 782 patients were evaluated using esi triage system. in this study, the validity and reliability of the esi triage system were investigated in the first level, which showed a sensitivity and specificity of 42.3% and 99.2%, respectively. in this study, the overall accuracy of patient prioritization was 40% in all patients, and 85% at the first level (32). the accuracies of the studied triage systems, based on the results of the systematic review, have been shown in table 2. 4. discussion the accuracy of the triage system indicates that the injured people have been classified properly, based on the severity of the injury, to receive medical services. so, misclassification of injured persons will lead to ineffective usage of medical resources and may cause avoidable death. the following criteria can be applied to determine the accuracy of triage systems such as sensitivity, specificity, positive/negative predictive value, and over-triage/under-triage. the sensitivity and specificity indicators show the correct prioritization of the injured and the predictive value indicates the power of the triage method in correct classification of these individuals. over-triage and under-triage would put the injured people in a wrong group compared to their real level of injury. this depends on the sensitivity and specificity levels of the triage system. over-triage will lead to provision of services more than what is needed for the patients, which in turn can lead to a waste of time and resources. on the contrary, under-triage, can lead to provision of less health services than needed, which can endanger the life of the person. although according to the previous studies, 50% over-triage and 5% under-triage are acceptable, needless to say, it is better to reduce over-triage and especially under-triage as much as possible (16, 18, 25, 26, 30). the closer the accuracy of a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 6 triage system is to 100%, it means that the patient is properly placed in the desired category and no patient is over-triaged or under-triaged, which is the ideal. when over-triage and under-triage are zero, the triage accuracy is 100% and no patient is missed or no resources are wasted. this is an ideal case, but triage systems are affected by various factors, such as the person who performs triage or the system and accuracy of triage tools, over-triage should be increased so that the disease does not get worse and under-triage goes to zero. in the present study, the range of accuracy was wide in all triage tools. the accuracy and effectiveness of mci triage systems’ analysis is limited, because there are no gold standard definitions for each triage category. unless there is agreement on which patients should be categorized in each triage category, it will be impossible to calculate the sensitivity and specificity or to compare the accuracy between the triage systems (33). in mass casualty incidents, the great number of injured patients, the limited resources (for example few professional health care providers and medical equipment), urgent need for medical services, and delay in provision of health services can endanger the lives of the injured patients (34). it should be mentioned that many factors can influence over-triage and under-triage (35). one of the prominent factors affecting the extent of over-triage and under-triage is the level of triage experts’ related knowledge and experience. in fact, if the triage performers do not possess the necessary training background and experience, the injured people will fall into wrong categories and hence, over-triage and under-triage rates will increase. the important issue is the situation in which the triage system is evaluated, either a scenario or real events, which are different and the person doing the triage is differently affected by triage error (35). the person doing the triage in a scenario situation has less environmental stress and is less affected by a triage error (36, 37). in addition, the person already has the necessary training and preparation for triage and his/her performance has improved, which results in improved triage accuracy (37, 38). other factors that affect the level of over-triage and undertriage include the type and the location of the incident, and the type of injury. the mechanism of the injury, affects the severity of injuries. as a result, if an incident, such as suicide, causes serious injuries to people, injured people are usually severely damaged and they are placed in the immediate or dead category. as for the type of injury, if the incident causes internal injury such as internal bleeding, or liver or spleen rupture, it may be impossible or difficult to detect these injuries using anatomical or physiological findings. so the injured person is placed in the wrong category and it will eventually result in an increase in over-triage or undertriage. the place of the event also affects the amount of overtriage and under-triage. if, for example, the event takes place in urban places, due to the availability of advanced medical equipment and services for detecting injuries, over-triage and under-triage rates decrease, whereas in rural and distant places, due to the lack of access to such equipment, over-triage and under-triage rates increase. in general, the time and amount of access to specialized medical equipment, especially in re-triage, affect over-triage and undertriage. when an incident occurs in the urban area, since the patient enters the specialized emergency system quickly and is treated quickly, he/she is less affected by the change in triage level. however, when the patient is far from a specialized center, such as in rural or road areas, the patient’s triage level changes because he/she may not receive appropriate treatment. finally, it can be said that a good triage system should have a high accuracy with the lowest level of overtriage and under-triage. one possible solution to increase the accuracy of triage systems is to increase the number of re-triage steps. increasing the number of re-triage steps can reduce over-triage and subsequently increase the triage accuracy, but conversely, it can increase under-triage and increase the duration of triage (17, 39, 40). the triage systems in different conditions do not use the same unit standards, which leads to achievement of different accuracies. to test the accuracy of triage systems around the world, there are two gold standards as references, and all triage systems are currently compared to them (35). the most important factor in classifying casualties is the severity of the injury and the possible consequences of death and recovery. in general, for determining the accuracy of triage systems, indicators such as sensitivity, specificity, positive and negative predictive values, overall accuracy, over-triage, and undertriage are used. once the triage systems are functioning properly, and the rates of over-triage and under-triage are low; however, some references have mentioned that even up to 50% over-triage is acceptable and under-triage should be less than 5% (41). sensitivity indicates the precise classification of the patient and specificity indicates the classification of healthy people in the correct category, both of which are closely related to the level of over-triage and under-triage. finally, a system is considered a desirable triage system, when it has an acceptable level of accuracy and can prioritize the patients in the correct order. as a result, the triage systems used in different parts of the world should be assessed for validity and reliability, and especially for accuracy (33). then, in case of deficiencies in the performance of these systems, their indicators could be corrected or changed, so that the accuracy level of these systems in patient prioritization would reach the optimal level. by doing so, the injured people will receive the required services without any problem, and even in some cases, their lives will not be compromised. triage tools are composed of different indicators. how acthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e32 curate an indicator is and how professionally it assesses the condition of the patient or the injured affects triage error. sometimes a triage system is designed for emergencies and disaster situations. it is natural that we will move to a triage system that is simple, convenient, and not complicated. this simplicity affects triage error. in addition, since time is valuable, we must accept the percentage of triage error so that we can prioritize the casualty more easily and quickly, which in turn leads to triage error. conversely, when we are in normal and routine conditions, we need a more accurate triage system because patients are triaged one by one and there is no problem in terms of resources, equipment and manpower, and it is natural that the rate of under-triage and over-triage in these conditions is lower. therefore, one of the factors that causes differences in triage tools is what indicators that tool consists of and whether it is designed for disaster conditions or routine conditions. secondly, the factor that greatly affects the differences between triage systems is that, unfortunately, many of the tests that have been performed have not used the reference gold standard (33). the error related to the triage tool is due to the indicators in the tool. for example, in the start triage, the breathing and pulse index have no range, but in the sieve and sort triage, there is a specific range. also, in the start triage, the walking wound index has no classification and only evaluates the ability to walk and not walk, but in the sieve tool, this indicator has three ranges, which can affect the accuracy of the triage tool (35). another issue is the allocation of the injured to different color categories, especially in testing the tool in scenario conditions, which affects the accuracy of the tool. for example, the start triage tool may be better at identifying the injured in the green group than in the red and yellow groups. the accuracy of this tool will automatically increase. unfortunately, there is no standard for allocating casualties to the categories (33, 35). 5. limitations there were some limitations observed in conducting this research: 1) studies have been done in different years. 2) they are not homogeneous, as they have examined populations with different age groups. 3) they have been conducted on people exposed to various incidents. 4) all triage systems are not studied in a single research. 5) studies have not compared all the indicators of accuracy in a single research and 6) they have failed to conduct studies in real disaster situations. 7) although 9 different triage systems were included in the study, few studies were found related to each system. for this reason, various aspects of triage systems in terms of accuracy have not been addressed adequately. 8) we just focused on articles published in english, other non-english articles were missed. 9) articles included in the study were not homogenous in terms of study population, as some used real cases while others were done based on scenario-based incidents. 6. conclusion according to the findings of the current systematic review, the performance of the existing triage systems in terms of accuracy of prioritizing the injured people and other performance indexes is not desirable. each country, usually based on its local context, chooses one of the triage systems or designs a new model. iran does not have any local hospital triage for disaster and mass casualty incidents conditions and it is advisable to develop a new national model to address this issue in iran. therefore, to improve the performance and increase the precision of triage systems, the world nations are recommended to change or revise the indexes used in triage models and also identify other influential factors affecting the accuracy of triage systems. this not only makes the resources and facilities available for the injured needing lifesaving interventions, but also prevents wasting the limited medical resources and/or endangering human lives. 7. declarations 7.1. acknowledgments we wish to thank all the researchers who helped us in this literature review. 7.2. author contribution jb, mf, and hrk conceptualized the study questions and performed revisions. jb, as, and hs performed the searches. jb, mf, as, hs, and hrk conducted the statistical analyses. jb, and hs provided the draft of the manuscript. all authors have read and approved the final draft of the manuscript. 7.3. funding and support the author(s) received no financial support for the research, authorship and/or publication of this article. 7.4. conflict of interest the authors have declared that no competing interests exist. 7.5. ethical considerations this research was approved by tehran university of social welfare and rehabilitation sciences and the code of ethics received was ir.uswr.rec.1398.07. all ethical principles were considered in this article. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 8 references 1. bazyar j, farrokhi m, khankeh h. triage systems in mass casualty incidents and disasters: a review study with a worldwide approach. open access maced j med sci. 2019;7(3):482-94. 2. cao h, huang s. 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comparative validation using data from 7th july bombings. injury. 2013;44(5):629-33. 19. stang a. critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. eur j epidemiol. 2010;25(9):603-5. 20. kariman h, joorabian j, shahrami a, alimohammadi h, noori z, safari s. accuracy of emergency severity index of triage in imam hossein hospital tehran, iran (2011). j gorgan univ med sci. 2013;15(1):115-20. 21. garner a, lee a, harrison k, schultz ch. comparative analysis of multiple-casualty incident triage algorithms. ann emerg med. 2001;38(5):541-8. 22. cambridge university press. salt mass casualty triage: concept endorsed by the american college of emergency physicians, american college of surgeons committee on trauma, american trauma society, national association of ems physicians, national disaster life support education consortium, and state and territorial injury prevention directors association. disaster med public health prep. 2013;2(4):245-6. 23. lampi m, vikström t, jonson c-o. triage performance of swedish physicians using the atls algorithm in a simulated mass casualty incident: a prospective crosssectional survey. scand j trauma resusc emerg med. 2013;21(1):90. 24. us department of health and human services. salt mass casualty triage algorithm (sort, assess, lifesaving interventions, treatment/transport) 2013 [available from: https://www.remm.nlm.gov/salttriage.htm. 25. cone dc, serra j, kurland l. comparison of the salt and smart triage systems using a virtual reality simulator with paramedic students. eur j emerg med. 2011;18(6):314-21. 26. wolf p, bigalke m, graf bm, birkholz t, dittmar ms. evaluation of a novel algorithm for primary mass casualty triage by paramedics in a physician manned ems system: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e32 a dummy based trial. scand j trauma resusc emerg med. 2014;22:50-. 27. slomian j, honvo g, emonts p, reginster j-y, bruyère o. consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes. women’s health. 2019;15:1745506519844044. 28. mckee ch, heffernan rw, willenbring bd, schwartz rb, liu jm, colella mr, et al. comparing the accuracy of mass casualty triage systems when used in an adult population. prehosp emerg care. 2020;24(4): 515-524. 29. franc jm, kirkland sw, wisnesky ud, campbell s, rowe bh. metastart: a systematic review and metaanalysis of the diagnostic accuracy of the simple triage and rapid treatment (start) algorithm for disaster triage. prehosp disaster med. 2022;37(1):106-116. 30. vassallo j, beavis j, smith je, wallis la. major incident triage: derivation and comparative analysis of the modified physiological triage tool (mptt). injury. 2017;48(5):992-9. 31. buschhorn hm, strout td, sholl jm, baumann mr. emergency medical services triage using the emergency severity index: is it reliable and valid? j emerg nurs. 2013;39(5):e55-e63. 32. platts-mills tf, travers d, biese k, mccall b, kizer s, lamantia m, et al. accuracy of the emergency severity index triage instrument for identifying elder emergency department patients receiving an immediate life-saving intervention. acad emerg med. 2010;17(3):238-43. 33. lerner eb, mckee ch, cady ce, cone dc, colella mr, cooper a, et al. a consensus-based gold standard for the evaluation of mass casualty triage systems. prehosp emerg care. 2015;19(2):267-71. 34. moskop jc, iserson kv. triage in medicine, part ii: underlying values and principles. ann emerg med. 2007;49(3):282-7. 35. bazyar j, farrokhi m, salari a, khankeh hr. the principles of triage in emergencies and disasters: a systematic review. prehosp disaster med. 2020;35(3):305-13. 36. forsgren s, forsman b, carlström ed. working with manchester triage – job satisfaction in nursing. int emerg nurs. 2009;17(4):226-32. 37. wolf l. the use of human patient simulation in ed triage training can improve nursing confidence and patient outcomes. int emerg nurs. 2008;34(2):169-71. 38. aysha zms, allam za. efficacy of start triage algorithm scenario-based education on nursing students’ knowledge, attitude, competencies, and clinical judgment. iosr j nurs health sci iosr-jnhs. 2020;9(1):39-56. 39. antonacci ac, lam s, lavarias v, homel p, eavey rd. benchmarking surgical incident reports using a database and a triage system to reduce adverse outcomes. arch surg. 2008;143(12):1192-7. 40. nordberg m, lethvall s, castrén m. the validity of the triage system adapt. scand j trauma resusc emerg med. 2010;18(s1):36. 41. beach m. disaster preparedness and management philadelphia, pa: f.a. davis co.; 2010 [available from: http://public.eblib.com/choice/publicfullrecord.aspx? p=3009628. 42. wallis la, carley s. comparison of paediatric major incident primary triage tools. emerg med j. 2006;23(6):475-8. 43. jones n, white ml, tofil n, pickens m, youngblood a, zinkan l, et al. randomized trial comparing two mass casualty triage systems ( jumpstart versus salt) in a pediatric simulated mass casualty event. prehospital emergency care. 2014;18(3):417-23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 10 table 1: : general characteristics of the studied articles that were eligible for the systematic review author system abstract finding study quality (nos) mary colleen bhalla(16); usa; 2015 salt, start the mechanism of injury was 41% motor vehicle collision, 32% fall, and 16% penetrating trauma. hospital outcome was 60% minor/green, 5% delayed/yellow, 29% immediate/red, and 6% dead/black. the salt method resulted in 5 over-triaged patients, 30 under-triaged, and 65 met triage level. the start method resulted in 12 over-triage, 33 under-triaged, and 55 at triage level. within triage levels, sensitivity ranged from 0% to 92%, specificity from 55% to 100%, positive predictive values from 10% to 100%, and negative predictive value from 65% to 97%. high christopher a. kahn(17); california; 2009 start field triage designations comprised 22 red (immediate), 68 yellow (delayed), and 58 green (minor) patients. outcome-based designations found 2 red, 26 yellow, and 120 green patients. seventy-nine patients were over-triaged, 3 were under-triaged, and 66 patients’ outcomes matched their triage level. no triage level met both the 90% sensitivity and 90% specificity requirement set forth in the hypothesis; yet, red was 100% sensitive and green was 89.3% specific. high david c. cone(25); sweden; 2011 salt, smart the students had a mean triage accuracy of 70.0% with salt versus 93.0% with smart (p =0.0001). mean over-triage was 6.8% with salt versus 1.8% with smart (p = 0.0015), and mean under-triage was 23.2% with salt versus 5.1% with smart (p = 0.0001). high alan garner(21); australia; 2001 careflight, start, mstart, sieve the differences between careflight triage, simple triage and rapid treatment, and modified simple triage and rapid treatment were not dramatic, with sensitivities of 82%, 85%, and 84%, respectively, and specificities of 96%, 86%, and 91%, respectively. high philipp wolf(26); germany; 2014 asav for red patients, sensitivity of asav was 87%, specificity 91%, over-triage 6%, and under-triage 10%. there were no significant differences between asav and mstart. asav triage required a mean of 35.4 sec per patient. high jamesvassallo(30); united kingdom; 2017 mptt the mptt had a sensitivity of 69.9% and specificity of 65.3%, and showed an absolute increase in sensitivity over existing tools ranging from 19.0% (modified military sieve) to 45.1% (triage sieve). high kariman h(20); iran; 2013 esi the sensitivity of triage for steps i, ii, iii, iv and v was 100%, 53.2%, 90.7%, 67.1%, and 98%, respectively. the specificity of triage for steps i, ii, iii, iv and v was 99.8%, 97.5%, 93.7%, 98.3%, and 94%, respectively. moderate buschhorn bh(31); usa; 2013 esi for esi level 1, ems providers were 0% sensitive and 97.3% specific. they were 94.7% accurate in their assignments of patients to, or not to, esi level 1. for esi level 2, the ems providers were 57.1% sensitive and 84.9% specific. their overall accuracy in assigning patients to, or not to, esi level 2 was 69.3%. in esi level 3, sensitivity was 67.9% and specificity was 68.1%. the accuracy of the prehospital providers in assigning patients to, or not to, esi level 3 was 68.0%. in esi level 4, prehospital provider sensitivity was 33.3%, specificity was 93.1%, and accuracy was 90.1%. moderate platts mills tf(32); carolina; 2010 esi the sensitivity of esi in identifying patients in need of receiving an immediate intervention was 42.3% (95% confidence interval [ci] = 23.3% to 61.3%); the specificity was 99.2% (95% ci = 98.0% to 99.7%). high wallis la(42); south african; 2006 careflight, jumpstart, start overall, the careflight score had the best performance in terms of sensitivity and specificity. the performance of the ptt was very similar. in contrast, the jumpstart and start scores had very low sensitivities, which meant that they failed to identify patients with serious injuries, and would have missed the majority of seriously injured casualties in the models of major incidents. high jones n(43); alabama; 2015 salt, jumpstart forty-three paramedics were enrolled. seventeen were assigned to the salt group with an overall triage accuracy of 66% ±15%, a mean over-triage rate of 22 ± 16%, and an under-triage rate of 10 ± 9%. twenty-six participants were assigned to the jumpstart group with an overall accuracy of 66 ± 12%, a mean over-triage rate of 23 ±16%, and an under-triage rate of 11.2 ± 11%. high mckee(28); usa; 2019 start, salt, sieve, careflight we found that salt triage most often correctly triaged adult emergency department patients compared to a previously published criterion standard. moderate france j.(29); global(systematic review); 2021 start proportion of victims correctly triaged using start ranged from 0.27 to 0.99 with an overall triage accuracy of 0.73 (95% ci, 0.67 to 0.78). proportion of over-triage was 0.14 (95% ci, 0.11 to 0.17), while the proportion of under-triage was 0.10 (95% ci, 0.072 to 0.14). there was significant heterogeneity among the studies for all outcomes (p < .0001). high start: simple triage and rapid treatment; mstart: modified simple triage algorithm and rapid treatment; salt: sort, assess, lifesaving interventions, treatment/transport; asav: amberg-schwandorf algorithm for primary triage; mptt: modified physiological triage tool; esi: emergency severity index. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e32 table 2: the accuracy of triage systems based on the results of the systematic review systems articles* accuracy# sensitivity specificity over-triage under-triage start 6 36 -73 39.2 – 90 78.7 90 12 53 2 33 mstart 2 84.8 84-88.2 91-93.9 3.8 6.8 salt 4 66 70 65 88.3 5 22 10 30 smart 1 93 1.8 5.1 care flight 3 36 39.2-96 96 98.8 5.6 57.6 asav 1 83.9 87.4 91 4.6 9.7 sieve 2 45 88 mptt 1 69.6 65.3 esi 3 40 94.7 42.3 – 100 93.7 99 data are presented as percentage. *: number of articles; #: overall accuracy. start: simple triage and rapid treatment; mstart: modified simple triage algorithm and rapid treatment; salt: sort, assess, lifesaving interventions, treatment/transport; asav: amberg-schwandorf algorithm for primary triage; mptt: modified physiological triage tool; esi: emergency severity index. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. bazyar et al. 12 figure 1: the prisma flow diagram of the present study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e16 or i g i n a l re s e a rc h correlation between timi risk score and the number of vessels involved in the angiographic study; a crosssectional study mohammad hasan namazi1, seyede salimeh mazloomi1∗, mohammad kalate aghamohammadi2 1. department of cardiology, moddares hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of internal medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2022; accepted: january 2022; published online: 14 february 2022 abstract: introduction: timi (thrombolysis in myocardial infarction) score is a model for predicting the severity of vascular diseases. this study aimed to evaluate the correlation between this score and the number of vessels involved in patients with unstable angina (ua) or non-st elevation myocardial infarction (nstemi). methods: this prospective cross-sectional study was designed to evaluate the correlation between timi score, and the number of vessels involved in the angiographic study of nstemi and ua patients presenting to emergency department. results: 297 patients with the mean age of 62.16±36.59 years were entered (58.2% male; 193 (65%) ua and 104 (35%) nstemi). the mean timi score among patients was 3.21±1.55. based on the timi score, patients were categorized into 3 groups. 105 (35.35%) patients had a timi score of 0 to 2, 120 (40.40%) had a score of 3 to 4, and 72 (24.24%) had a score of 5 to 7. patients with a timi score of 5 to 7 had a greater likelihood of three-vessel coronary artery disease compared to patients with a timi score of 3 to 4 (or: 5.34, 95% ci: 2.64 to 10.80; p < 0.0001) or those with a timi score of 0 to 2. (or: 29.45, 95% ci: 12.87 to 67.37; p < 0.0001). two-vessel coronary artery disease was more likely to be found in patients with a timi score of 3 to 4 or those with a score of 5 to 7 compared to patients with a timi score of 0 to 2 (or: 3.69, 95% ci: 1.60 to 8.51; p <0.0001 and or: 2.67, 95% ci: 1.04 to 6.82; p = 0.04, respectively). conclusion: there is a direct and significant correlation between timi score and the number of coronary vessels involved in patients presenting to emergency department following ua or nstemi. keywords: myocardial infarction; risk assessment; coronary circulation; non-st elevated myocardial infarction cite this article as: namazi m, mazloomi ss, kalate aghamohammadi mk. correlation between timi risk score and the number of vessels involved in the angiographic study; a cross-sectional study. arch acad emerg med. 2022; 10(1): e16. https://doi.org/10.22037/aaem.v10i1.1466. 1. introduction advancements of cardiac care units and revascularization methods, as well as the developments in pharmacotherapy, have led to improved patient outcomes after acute coronary syndrome (acs) (1, 2). despite recent developments, coronary artery disease (cad) remains the leading cause of death across the world. myocardial infarction (mi) is known as the most severe presentation of cad and cad accounts for 30% of all mortalities (3). each year, three million people expe∗corresponding author: seyede salimeh mazloomi; department of cardiology, moddares hospital, shahid beheshti university of medical sciences, tehran, iran. e-mail: salimeh.mazloomi@protonmail.com, tel: +989122966448, orcid: http://orcid.org/0000-0003-3044-8917. rience st-segment elevation mi (stemi) and also non-stsegment elevation mi (nstemi) was estimated to occur in about four million (4). several randomized clinical trials performed in the past two decades have established that immediate and complete restoration of flow in the occluded artery decreases infarct size, improves survival rates, and preserves left ventricular (lv ) function (5, 6). choosing the best treatment in the initial stages following quick diagnosis is of great importance in improving the outcome. nonetheless, electrocardiogram (ecg), as the most readily available diagnostic tool in chest pain units, is not adequately helpful in decision making(7). the timi (thrombolysis in myocardial infarction) research group has introduced a specific model, the timi risk score assessment tool, which has been found to be predictive of the severity of vascular diseases and the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. namazi et al. 2 potential of coronary circulation involvement in chest pain patients (8). there are seven components used in the calculation of the timi score. patients presenting with unstable angina (ua) or nstemi that fit score 3 or more on the timi model are mostly recommended to undergo early invasive management with cardiac angiography and revascularization if necessary (9). the timi score was established as one of the most commonly utilized risk assessment models in the chest pain units to warrant further workup. hence, the development of the timi risk score originated from developed countries, with limited data evaluating the effectiveness in developing countries. this is particularly important for lower-middle-income countries, which are increasingly affected by cardiovascular disease epidemic and encompass different genetics and lifestyle. this study aimed to evaluate the correlation between timi risk score and the number of vessels involved in the angiographic study of patients presenting to emergency department following ua or nstemi. 2. methods 2.1. study design and setting this prospective cross-sectional study was designed to evaluate the correlation between timi score, and the number of vessels involved in the angiographic study of nstemi and ua patients, presenting to modarres hospital, tehran, iran, from april 2019 to august 2020. the study was approved by the ethics committee of shahid beheshti university of medical sciences (code: ir.sbmu.retech.rec.1398) and the researchers adhered to the principles of the helsinki declaration and patient data confidentiality throughout the study. written informed consent was obtained from all the patients for participating in the study. 2.2. participants patients with ua or nstemi who underwent angiographic study were included in the study using census sampling method. patients with unclear past medical history or past coronary angiographic history, prior coronary artery bypass graft (cabg), atypical chest pain, evidence of st-segment elevation in the initial ecg, those who underwent the angiographic procedure due to reasons other than ischemic heart disease, and those who did not give consent for participating were excluded. 2.3. data gathering data on baseline characteristics, including demographics (age, sex), risk factors (weight, hypertension, diabetes, current smoking, family history of coronary artery disease), and medical history (prior angina or mi), were collected. timi score predictive factors (presence of at least three risk factors for coronary artery disease, age of 65 years or older, presence of 2 or more episodes of angina 24 hours before the presentation, aspirin use in the past seven days, previous history of coronary stenosis of 50% or more, st-segment deviations greater than or equal to 0.05 mv on initial ecg on admission, elevated serum cardiac markers of necrosis) and angiographic data were also included in the checklist. coronary artery angiography was done and reported by one expert cardiologist. stenosis of the coronary artery was given a score of 0 if narrowing was less than 50% and a score of 1 if stenosis was greater than 50%. echocardiography study was done by an expert cardiologist at the time of admission using vivid® s6 ge device. cardiologists who performed the angiographies and echocardiographs were blinded to the timi scores of patients. 2.4. timi score the following seven factors help assess the mortality risk: 1. presence of at least three risk factors for coronary artery disease (i.e., diabetes mellitus, hypertension, hyperlipidemia, smoking, family history). 2. age of 65 years or older. 3. presence of 2 or more episodes of angina 24 hours before the presentation. 4. aspirin use in the past seven days. 5. previous history of coronary stenosis of 50% or more. 6. st-segment deviations more than or equal to 0.05 mv on ecg on admission. 7. elevated serum cardiac markers of necrosis. each factor has a value of one point. a higher score implies a higher likelihood of mortality. the risk of mortality and need for further invasive cardiac intervention for each score is as follows: • 4.7% for a score of 0/1 • 8.3% for a score of 2 • 13.2% for a score of 3 • 19.9% for a score of 4 • 26.2% for a score of 5 • 40.9% for a score of 6/7 scores ranging from 0-2 represent a low risk. scores from 3-5 are considered to point to intermediate risk. a score of 6 or 7 indicates high risk (10). 2.5. statistical analysis patient characteristics were summarized using frequency (%) or mean ± standard deviation. logistic regression analysis was used to assess the correlation between the timi risk and severity of cad. results are presented as odds ratios (ors) with corresponding 95% confidence intervals (cis) and ibm spss 23.0 was used to perform statistical analyses. (ibm spss inc., chicago, il). for all analyses, two-sided p values <0.05 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e16 table 1: baseline characteristics of the studied patients variables timi score p total n=297 0-2 n=105 3-4 n=120 5-7 n=72 sex male 173 (58.2) 67 (63.8) 65 (54.2) 41 (56.9) 0.33 female 124 (41.8) 38 (36.2) 55 (45.8) 31 (43.1) diagnosis unstable angina 193 (65.0) 84 (80.0) 77 (64.2) 32 (44.4) < 0.001 nstemi 104 (35.0) 21 (20.0) 43 (35.8) 40 (55.6) cad risk factor diabetes mellitus 112 (37.7) 18 (17.1) 56 (46.7) 38 (52.8) < 0.001 smoking 134 (45.1) 49 (46.7) 52 (43.3) 33 (45.8) 0.87 hypertension 183 (61.6) 48 (45.7) 75 (62.5) 60 (83.3) < 0.001 dyslipidemia 159 (53.5) 43 (41.0) 64 (53.3) 52 (72.2) < 0.001 family history of cad 75 (25.3) 19 (18.1) 32 (26.7) 24 (33.3) 0.06 ectatic vessels number 26 (8.8) 12 (11.4) 12 (10.0) 2 (2.8) 0.11 data are presented as number (%). cad: coronary artery disease; nstemi: non-st segment elevation myocardial infarction. table 2: frequency of timi risk score variables in the study population age of 65 years or older 116 (39.1) st-segment deviations ≥0.05 mv on initial ecg on admission 136 (45.8) presence of ≥ 2 episodes of angina 24 hours before the presentation 225 (75.8) aspirin use in the past seven days 185 (62.3) previous history of coronary stenosis of 50% or more 46 (15.5) elevated serum cardiac markers of necrosis 103 (34.7) presence of at least three risk factors for coronary artery disease 136 (45.8) data are presented as number (%). ecg: electrocardiogram. table 3: correlation between timi score and number of coronary arteries involved involvement* total timi score p 0-2 n=105 3-4 n=120 5-7 n=72 normal/nonsignificant 62 (20.9) 53 (50.5) 9 (7.5) 0 (0.0) < 0.001 one vessel 68 (22.9) 32 (30.5) 34 (28.3) 2 (2.8) < 0.001 two vessels 49 (16.5) 8 (7.6) 28 (23.3) 13 (18.1) < 0.001 three vessels 118 (39.7) 12 (11.4) 49 (40.8) 57 (79.2) < 0.001 data are presented as number (%). *: number of coronary artery vessels involved in angiography. were considered significant. 3. results 3.1. baseline characteristics of studied patients 297 patients with mean age of 62.16±36.59 years who presented with acute coronary syndrome and underwent coronary angiography during the study period were entered (58.2% male). 193 (65%) were diagnosed with ua and 104 (35%) with nstemi. the mean ejection fraction within the study population was 48.68%±10.25%. among the studied cases, 27 (9%) patients were categorized as having severe systolic dysfunction with an ef of 30% or less. the mean number of significant coronary lesions was 1.75±1.18 vessels. 26 (8.8%) patients had ectatic coronary vessels in angiography. tables 1 and 2 show the baseline characteristics of the patients. the mean timi score among patients was 3.21±1.55. based on the timi score, patients were categorized into 3 groups. 105 (35.35%) patients had a timi score of 0 to 2, 120 (40.40%) had a score of 3 to 4, and 72 (24.24%) had a score of 5 to 7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. namazi et al. 4 3.2. correlation of timi score and number of vessels involved table 3 summarizes the correlation between timi score and the number of coronary arteries involved. patients with a timi score of 5 to 7 had a greater likelihood of three-vessel coronary artery disease compared to patients with a timi score of 3 to 4 (or: 5.34, 95% ci: 2.64 to 10.80; p < 0.0001) or those with a timi score of 0 to 2 (or: 29.45, 95% ci: 12.87 to 67.37; p < 0.0001). two-vessel coronary artery disease was more likely to be found in patients with a timi score of 3 to 4 or those with a score of 5 to 7 compared to patients with a timi score of 0 to 2 (or: 3.69, 95% ci: 1.60 to 8.51; p <0.0001 and or: 2.67, 95% ci: 1.04 to 6.82; p = 0.04, respectively). one-vessel cad was also seen more often in patients with a score of 0 to 2 compared to patients with a score of 3 to 4 or 5 to 7 (or: 15.34, 95% ci: 3.54 to 66.42; p< 0.0001 and or: 13.83, 95% ci: 3.21 to 59.61; p < 0.0001). no statistically significant correlation was found between non-significant cad angiographic finding and timi score. 4. discussion patients with nstemi are older and have multiple cardiovascular risk factors, as well as an increased risk of cardiovascular complications. hence, the timi risk score was found to be helpful in the identification of high-risk patients. this study was conducted to assess the correlation of the number of occluded vessels with timi risk score. the main findings of this study demonstrated that timi score appears to be a practical tool for identifying high-risk patients after ami, particularly in relation to the number of vessels with thrombus, and can also predict the findings in angiography follow-up. in this study, data were collected from a group of 297 patients who presented to our center with signs or symptoms of ua or nstemi; their timi score calculated at the time of admission significantly correlated with the number of occluded vessels and severity of ischemia later found in the angiographic study (average timi score was 3.2 vs. average number of occluded vessels 1.8). most patients were men younger than 65 years old and diagnosed with unstable angina. our study revealed that timi score significantly increased with an increase in the number of vessels involved in thrombotic obstruction (p-value=0.001, r= 0.639). the correlation was found in both groups of ua and nstemi. timi score has been validated by the tactics-timi trial (11) and prism-plus trial (12). also, based on the essence trials (13) and timi iib (9) study, the timi risk score incorporates the predictive factors of clinical characteristics, ecg changes, and cardiac biomarkers for risk assessment. this score also identifies high-risk patients and determines whether an immediate invasive strategy would be beneficial in such patients (14). garcia et al. demonstrated that the score has broader usefulness in risk stratification and is easy to use as a bedside tool (15). in their experience, a cutoff of 5 and more in timi score distinguished patients with 3-vessel or left main disease from those without these diseases. however, the final decision regarding which revascularization technique should be used in any patient will be made in the cardiac catheterization laboratory (15). abbas et al. revealed that higher timi scores (>4) in patients were associated with a greater extent of cad (16). this classification not only aids in the management of limited resources but also helps avoiding unnecessarily imposing adverse outcomes of invasive techniques on patients at lower risk. on the other hand, an invasive strategy, namely routine coronary angiography, is recommended for patients at high or moderate risk. the results of our study are compatible with the findings of the study by mega et al. (17), who concluded that the mean timi risk score of 3 reflects a higher risk. they furthermore showed that despite similar timi risk scores, inhospital outcomes in patients with acs have improved over time (1998 through 2000), and correlated this change with the greater use of newer antiplatelet and antithrombotic therapies, such as glycoprotein and low molecular weight heparin, and the increased availability of intracoronary stenting. also, roffi concluded that patients with risk scores of more than 4 were more likely to have critical stenosis (81% vs 58%, p<0.001) and multi-vessel disease (80% vs 43%, p<0.001) (7). it seems that, timi score enables us to predict the presence of significant coronary artery lesions, as well as the severity of stenosis and prognosis of patients undergoing thrombolytic therapy. furthermore, it can help us reap the benefits of early intervention therapy in patients. 5. limitation there are several limitations to our study. the results of the study are significant; however, larger cohorts are required to assess the accuracy of the timi score in predicting the severity of obstructed vessels. the study does not include short or long-term follow-ups, which can develop stronger data about the prognostic aspect of timi score. finally, our results are derived from an observational study on the limited population of patients referring for angiography, and may not apply to the entire population of patients. in addition, our analyses were not focused on mortality. 6. conclusion based on the findings of present study, there is a direct and significant correlation between timi score and the number of coronary vessels involved in patients presenting to emergency department following ua or nstemi. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e16 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions conceptualization: mohammad hasan namazi. data curation: seyede salimeh mazloomi, mohammad kalate aghamohammadi. formal analysis: seyede salimeh mazloomi, mohammad kalate aghamohammadi. methodology: mohammad hasan namazi, seyede salimeh mazloomi. project administration & supervision & validation: mohammad hasan namazi. writing – original draft, review & editing: all authors. 7.3. funding and supports no funding was received for this study. 7.4. conflict of interest no potential conflict of interest was reported by the authors. references 1. anderson jl, morrow da. acute myocardial infarction. new england journal of medicine. 2017;376(21):2053-64. 2. yeh rw, sidney s, chandra m, sorel m, selby jv, go as. population trends in the incidence and outcomes of acute myocardial infarction. new england journal of medicine. 2010;362(23):2155-65. 3. deaton c, froelicher es, wu lh, ho c, shishani k, jaarsma t. the global burden of cardiovascular disease. european journal of cardiovascular nursing. 2011;10(2_suppl):s5-13. 4. white hd, chew dp. acute myocardial infarction. the lancet. 2008;372(9638):570-84. 5. widimsky p, wijns w, fajadet j, de belder m, knot j, aaberge l, et al. reperfusion therapy for st elevation acute myocardial infarction in europe: description of the current situation in 30 countries. european heart journal. 2010;31(8):943-57. 6. damman p, woudstra p, kuijt wj, kikkert wj, hoef tp, grundeken mj, et al. shortand long-term prognostic value of the timi risk score after primary percutaneous coronary intervention for st-segment elevation myocardial infarction. journal of interventional cardiology. 2013;26(1):8-13. 7. roffi m, patrono c, collet jp, mueller c, valgimigli m, andreotti f, et al. 2015 esc guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the european society of cardiology (esc). european heart journal. 2016;37(3):267-315. 8. rao ss, agasthi p. treasure island (fl): statpearls publishing. 2020 updated 2021 feb 14. available from: https://www.ncbi.nlm.nih.gov/books/nbk556069/?report=classic. 9. antman em, cohen m, bernink pj, mccabe ch, horacek t, papuchis g, et al. the timi risk score for unstable angina/non–st elevation mi: a method for prognostication and therapeutic decision making. jama. 2000;284(7):835-42. 10. morrow da, antman em, snapinn sm, mccabe ch, theroux p, braunwald e. an integrated clinical approach to predicting the benefit of tirofiban in non-st elevation acute coronary syndromes. application of the timi risk score for ua/nstemi in prism-plus. eur heart j 2002;23(3):223-9. 11. puymirat e, bonaca m, fumery m, tea v, aissaoui n, lemesles g, et al. atherothrombotic risk stratification after acute myocardial infarction: the thrombolysis in myocardial infarction risk score for secondary prevention in the light of the french registry of acute st elevation or non-st elevation myocardial infarction registries. clinical cardiology. 2019;42(2):227-34. 12. cantor wj, goodman sg, cannon cp, murphy sa, charlesworth a, braunwauld e, et al. early cardiac catheterization is associated with lower mortality only among high-risk patients with st-and non–stelevation acute coronary syndromes: observations from the opus-timi 16 trial. american heart journal. 2005;149(2):275-83. 13. sociedadebrasileiradecardiologia. guidelines for unstable angina and non-st-segment elevation myocardial infarction of the brazilian society of cardiology (ii edition, 2007). arquivos brasileiros de cardiologia. 2007;89(4):e89-131. 14. terkelsen cj, lassen jf, nørgaard bl, gerdes jc, jensen t, gøtzsche lb, et al. mortality rates in patients with stelevation vs. non-st-elevation acute myocardial infarction: observations from an unselected cohort. european heart journal. 2005;26(1):18-26. 15. garcia s, canoniero m, peter a, de marchena e, ferreira a. correlation of timi risk score with angiographic severityand extent of coronary artery disease in patients with non–st-elevation acute coronary syndromes. the american journal of cardiology. 2004;93(7):813-6. 16. abbas s, siddiqui ah, cheema a, abbas a, jaffri sk, khan s, et al. association of thrombolysis in myocardial infarction (timi) risk score with extent of coronary artery disease in patients with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. namazi et al. 6 unstable angina and nstemi. pakistan armed forces medical journal. 2020;70 (suppl-4):s787-91. doi: 10.1017/cjn.2020.146 17. almeda fq, hendel rc, nathan s, meyer pm, calvin je, klein lw. improved in-hospital outcomes in acute coronary syndromes (unstable angina/non-st segment elevation myocardial infarction) despite similar timi risk scores. the journal of invasive cardiology. 2003;15(9):502-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e14 https://doi.org/10.22037/aaem.v9i1.1058 rev i ew art i c l e late complications of covid-19; a systematic review of current evidence seyedahmad seyedalinaghi1, amir masoud afsahi2, mehrzad mohssenipour1, farzane behnezhad3, mohammad amin salehi1, alireza barzegary4, pegah mirzapour1, esmaeil mehraeen5∗, omid dadras6 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. department of radiology, school of medicine, university of california, san diego (ucsd), california, usa. 3. department of virology, school of public health, tehran university of medical sciences, tehran, iran. 4. school of medicine, islamic azad university, tehran, iran. 5. department of health information technology, khalkhal university of medical sciences, khalkhal, iran. 6. department of global health and socioepidemiology, graduate school of medicine, kyoto university, kyoto. japan. received: december 2021; accepted: december 2021; published online: 20 january 2021 abstract: introduction: covid-19 is a new rapidly spreading epidemic. the symptoms of this disease could be diverse as the virus can affect any organ in the body of an infected person. this study aimed to investigate the available evidence for long-term complications of covid-19. methods: this study was a systematic review of current evidence conducted in november 2020 to investigate probable late and long-term complications of covid-19. we performed a systematic search, using the keywords, in online databases including pubmed, scopus, science direct, up to date, and web of science, to find papers published from december 2019 to october 2020. peerreviewed original papers published in english, which met the eligibility criteria were included in the final report. addressing non-human studies, unavailability of the full-text document, and duplicated results in databases, were characteristics that led to exclusion of the papers from review. results: the full-texts of 65 articles have been reviewed. we identified 10 potential late complications of covid-19. a review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) are the most frequent late complications of covid-19. conclusion: since we are still at the early stages of the covid-19 epidemic, it is too soon to predict what long-term complications are likely to appear in the survivors of the disease in years after recovery. furthermore, the complexity of covid-19 behaviors and targets in the human body creates uncertainty in anticipating long-term complications. keywords: long term adverse effects; late onset disorders; covid-19; sars-cov-2; post-acute covid-19 syndrome cite this article as: seyedalinaghi sa, afsahi a m, mohssenipour m, behnezhad f, salehi m a, barzegary a, mirzapour p, mehraeen e, dadras o. late complications of covid-19; a systematic review of current evidence. arch acad emerg med. 2021; 9(1): e14. 1. introduction coronavirus disease 2019 (covid-19) is an extremely contagious infectious disease caused by sars-cov-2 (1). covid19 infection was first reported in wuhan, china, and spread quickly and turned into an unprecedented global pandemic (2-5). the novel coronavirus affects not only the respiratory ∗corresponding author: esmaeil mehraeen, department of health information technology, khalkhal university of medical sciences, khalkhal, iran. postal code: 1419733141. tel: +98-21-66581583, fax: +98-21-66947984, email: es.mehraeen@gmail.com. tract, but also other organs in the human body. covid-19 could cause injuries in the lungs, liver, kidney, heart, vessels, and other organs (6). respiratory failure and acute respiratory distress syndrome (ards) are the most common complications of severe covid-19 infection; the majority of hospitalized covid-19 patients suffer from severe lung injuries and fatal multi-organ failure as well as hemolytic anemia. however; super infection, acute liver, kidney, and cardiac injuries, shock, and hypoxic encephalopathy are less common symptoms (7-9). some covid-19 patients may also present signs of tissue damage including rhabdomyolysis or hemoptysis, which lead to cellular injury, release of heme proteins, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 2 and collection of heme in body tissues (10). sars-cov-2 usually affects the respiratory system (11), nervous system involvement has also been reported in some recent studies among patients with covid-19 (12). coronaviruses can attack the neural tissue including microglia, astrocytes, and macrophages, and cause nerve injury through direct nerve infection (13). the nervous system injuries could manifest as headache, dizziness, seizure, impaired consciousness, acute cerebrovascular disease, and ataxia. the virus could also affect the peripheral nervous system (pns) and cause olfactory dysfunction, dysgeusia, vision impairment, and neuropathic pain (12, 13). covid-19 could also cause cardiac injuries such as cardiomyopathy and conduction system malfunction. studies suggest the direct involvement of cardiac muscles in some patients (4, 14, 15). generally, infectious myocarditis is the most common cardiac complication of covid-19 infection. sars-cov-2 uses the angiotensinconverting enzyme 2 (ace2) receptors to infect host cells, through which it can cause pneumonia and myocardial injuries. high expression of ace2 receptors in the lungs and heart could increase the risk of myocardial injuries in covid19 patients (14). ace2 is also expressed in the intravascular endothelium, intestinal epithelium, and the kidneys; therefore, these organs could be a target for sars-cov-2 infection. tachyarrhythmia is also a common cardiovascular complication in covid-19 patients. electrocardiography and echocardiography could be used in diagnosing and predicting the prognosis in covid-19 patients (16). some covid-19 patients could suffer from earache that may be a sign of sub-acute thyroiditis. studies have shown that a few weeks after upper respiratory tract involvement, subacute thyroiditis may occur and it might be a late complication in patients with covid-19 infection. therefore, thyroid functions should be checked after discharge in patients with covid-19 (17, 18). in addition, there is an abnormal rise in various biochemical parameters such as erythrocyte sedimentation rate (esr), albumin levels, serum ferritin levels, lactate dehydrogenase (ldh) levels, and c-reactive protein (crp) levels in the infected patients; on the other hand, the hemoglobin levels and lymphocyte count could reduce in these patients. these complications could lead to cytokine storm, causing multiple organ dysfunction (19, 20). the coronavirus pandemic showed that covid-19 could affect many organs besides the lungs, like heart and brain, which increases the risk of long-term health problems. there are several ways that the infection can affect someone’s health. much is still unknown about how covid-19 will affect people over time. while most patients infected with covid-19 recover quickly, the potential long-lasting problems caused by covid-19 make it necessary to look for and study its late complications. this review aims to present a systematic review of late complications of covid-19 and identify how prevalent these symptoms are and who is most likely to be affected by them. 2. methods 2.1. study design and setting this study was a systematic review of current evidence conducted in october 2020 and subsequently updated on november 4, 2020. the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist was employed. 2.2. data sources we performed a systematic search using the keywords in the online databases including pubmed, scopus, science direct, up to date, and web of science. all the related papers and reports published in english from december 2019 through october 2020 were retrieved and then updated in november 2020. our search strategy in each of the above-mentioned databases included several combinations of keywords in the following orders: a. “coronavirus” or “covid-19”or“sars-cov-2” or “novel coronavirus” or “2019-ncov" [title/abstract] b. "clinical characteristics” or “clinical feature” or “clinical manifestation" [title/abstract] c. "consequences” or “chronic complications” or“ late complications” or “long-term effects" [title/abstract] d. [a] and [b] and [c] 2.3. study selection the most relevant studies based on titles and abstracts were retrieved by three independent investigators. the full contents of the retrieved papers were reviewed, and the most relevant papers were selected based on the eligibility criteria. the relevant data were extracted and organized in tables. the peer-reviewed original papers published in english that met the eligibility criteria were included in the final report. the exclusion criteria were as follows: – papers addressing non-human studies including in vitro investigations or publications concentrating on animal experiments, or discussing covid-19 in general, without reference to the keywords of this study. – unavailability of the full-text document. – duplicated results in databases. 2.4. data extraction we used the data extraction sheet (table 2) to summarize the information of the authors, type of article (e.g., case series), country of origin, study population, and clinical symptoms (late complications in this study). two independent investigators gathered this information and further organized them in the tables. all the selected articles were cross-checked by other authors to ensure no duplications or overlap exists in the content. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e14 2.5. quality assessment for bias risk assessment, two independent reviewers rated the quality of included studies by applying the national institute of health (nih) quality assessment tools for case series studies. for this purpose, we have designed a table and evaluated the studies according to nih questionnaire (table 1). a third independent investigator was consulted to resolve probable difference of opinions in any case. the full text of select articles was fully read and the key findings were extracted. the final report including the key findings is summarized in table 2. 3. results we retrieved 1325 documents using a systematic search strategy. after an initial review of retrieved articles, 542 duplicates were removed, and the titles and abstracts of the remaining 783 articles were reviewed. applying the selection criteria, 718 articles were excluded, and only 65 articles met the inclusion criteria and were included in the final review (figure 1). we identified 10 potential late complications of covid-19 including neurological injuries, lung, liver, kidney, and heart injuries, thromboembolism, cardiac/brain stroke, encephalopathy, and psychological distress. furthermore, some studies have pointed out other complications such as hypoproteinemia, septic shock, and multiple organ dysfunction syndromes (table 1). review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) were the most frequent late complications of covid-19. frequencies of identified late complications of covid-19 are demonstrated in figure 2. 4. discussion one of the most important unknown features of covid-19 is the duration of symptoms. in the early stages of the disease, the experts believed that the recovery time for mild cases of covid-19 is 1-2 weeks (21). however, later in many patients, the symptoms lasted for 8 to 10 weeks or even longer, and in some cases, the initial symptoms were replaced by long-term complications such as lung or cardiac injuries (22). since covid-19 is a novel virus, there are limited studies about its late complications; it is just a few months since the recovery of the first patients in china. however, the available evidence suggests that the coronavirus can cause long-term complications in an infected person as it may cause major injuries to the heart, kidneys, brain, and even blood vessels (6, 10, 23, 24). the available evidence indicates the recurrence of symptoms in some patients who presented with severe initial symptoms (2, 25, 26). the key question is “what causes the recurrence of symptoms?”. it may be caused by the recurrence or persistence of the primary covid-19 infection or super infection with another virus or even bacteria due to the compromised immune system (27). in addition, the systemic and multiorgan involvement in advanced phases of covid-19 pneumonia can cause renal failure, liver dysfunction, thrombocytopenia, and coagulation disorders (28). therefore, the survivors may present a variety of long-term complications in different organs, including a post-recovery syndrome that doctors call "post-covid lung disease" (29). by looking at the organs affected during an infection, one can imagine what organs are likely to be affected by longterm complications of covid-19 infection (30). the most common long-term complication of covid-19 is lung disease (8, 29, 31). most of the covid-19 patients could be recovered completely except for some minor complications such as cough and shortness of breath. however, a certain proportion of patients have excessive lung damage, and some of them develop pulmonary fibrosis (32). autopsy studies demonstrated the predominance of microvascular thrombosis in the lungs, coincident with markers of inflammation, which is a hallmark of prolonged infection and sepsis (33). severe lung involvement in covid-19 patients could increase the likelihood of progression to chronic lung disease and lead to long-term complications (8, 33). covid-19 patients may experience both venous and arterial thrombosis due to severe inflammation and hypoxia, long immobilization, and diffuse intravascular coagulation (27, 28). klok et al. reported the incidence rate of thrombotic complications to be 31% among icu patients with severe covid-19 infection (27). the results of another study reported the high number of arterial and, in particular, venous thrombo-embolic late complications (34). poggiali et al. described two patients with covid-19 pneumonia who developed venous thromboembolism and reported hypoxia and sepsis as the potential risk factors for vein thromboembolism (vte)(35). recent studies reported an increased risk of heart failure in covid19 patients (26, 28, 30). moreover, episodes of clinical myocarditis have been observed (15). heart injuries related to covid-19 may occur over the course of the disease(36). late involvement of cardiac muscle has been documented in a study by puntmannet al. in this study, the researchers investigated the cardiac complications in 100 recovered patients; 78% of patients had cardiac involvement in cardiac magnetic resonance imaging (mri), 76% had detectable highsensitivity troponin, and 60% had abnormal native t1 and t2, which indicates the presence of active myocardial (37). compared to the control group with similar preexisting conditions, left ventricle ejection fraction was lower and the ventricular size was higher in covid-19 patients. in addition, 32% of patients had late gadolinium enhancement and 22% of them had pericardial involvement (36, 37). covid-19 can cause damage to the central nervous system, with pothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 4 tentially long-term consequences (38-41). late neurological complications of covid-19, whether caused by the virus or by the triggered inflammation, include decreased awareness and absorption, disturbed memory, and dysfunction of the peripheral nervous system (42). in one study from china, more than a third of hospitalized patients with confirmed covid-19 had neurological symptoms, including dizziness, headaches, impaired consciousness, vision, taste/smell impairment, and nerve pain. these symptoms were more common in patients with severe disease, where the incidence increased to almost 47 percent (43). another study in france found neurologic features in 58 of 64 critically ill covid-19 patients (25). 5. conclusion since we are still at the early stages of the covid-19 epidemic, it is too soon to predict what long-term complications are likely to appear in the survivors of the disease in years after recovery. furthermore, the complexity of covid-19 behaviors and variety of its targets in the human body create uncertainty in anticipating long-term complications. however, several ongoing studies are set up to examine the physical, psychological, and socio-economic consequences of the covid-19. 6. declarations 6.1. acknowledgment the present study was conducted in collaboration with khalkhal university of medical sciences, iranian institute for reduction of high-risk behaviors, tehran university of medical sciences, and department of global health and socioepidemiology, kyoto university. 6.2. author contributions (1) the conception and design of the study: esmaeil mehraeen, seyedahmad seyedalinaghi (2) acquisition of data: amir masoud afsahi, mehrzad mohssenipour (3) analysis and interpretation of data: farzane behnezhad, mohammad amin salehi, alireza barzegary (4) drafting the article: pegah mirzapour, esmaeil mehraeen (5) revising it critically for important intellectual content: seyedahmad seyedalinaghi, omid dadras (6) final approval of the version to be submitted: esmaeil mehraeen, omid dadras 6.3. ethics approval and consent to participate the present study was extracted from the research project with code ir.khalums.rec.1399.001 entitled "investigation of effective drugs for people affected by coronavirus disease 2019 (covid-19) in selected hospitals in ardabil" conducted at khalkhal university of medical sciences in 2020. 6.4. funding this research did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors. 6.5. consent to publication not applicable 6.6. availability of data and material the 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covid-19 and hematology-what do we know so far? sn compr clin med. 2020:1-6. 78. msigwa ss, wang y, li y, cheng x. the neurological insights of the emerging coronaviruses. j clin neurosci. 2020;78:1-7. 79. sheikh ab, shekhar r, javed n, upadhyay s. inferior wall myocardial infarction in severe covid-19 infection: a case report. am j case rep. 2020;21:e926101. 80. siripanthong b, nazarian s, muser d, deo r, santangeli p, khanji my, et al. recognizing covid-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management. heart rhythm. 2020;17(9):1463-71. 81. vonck k, garrez i, de herdt v, hemelsoet d, laureys g, raedt r, et al. neurological manifestations and neuroinvasive mechanisms of the severe acute respiratory syndrome coronavirus type 2. eur j neurol. 2020;27(8):1578this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 8 87. 82. wijeratne t, sales c, karimi l, crewther sg. acute ischemic stroke in covid-19: a case-based systematic review. front neurol. 2020;11:1031. 83. yachou y, el idrissi a, belapasov v, ait benali s. neuroinvasion, neurotropic, and neuroinflammatory events of sars-cov-2: understanding the neurological manifestations in covid-19 patients. neurol sci. 2020;41(10):265769. 84. zaim s, chong jh, sankaranarayanan v, harky a. covid-19 and multiorgan response. curr probl cardiol. 2020;45(8):100618. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e14 table 1: quality ratings of included studies based on nih quality assessment (qa) tool for case series studies first author *question rating 1 2 3 4 5 6 7 8 9 # 1 # 2 ali sepehrinezhad (21) yes yes cd cd na yes cd na yes fair fair filatov a (22) yes yes cd cd na yes cd yes yes fair fair helms j (25) yes yes na cd na yes cd yes yes fair fair heneka mt (2) yes yes cd cd na yes cd yes yes fair fair kochi an (26) yes yes cd cd na yes cd na yes fair fair klok fa (27) yes yes na cd na yes cd na yes fair fair klok fa (30) yes yes nr na na yes cd yes yes fair fair klok fa(30) yes yes cd cd na yes cd na yes fair fair kunutsor sk(44) yes yes cd na na yes cd yes yes fair fair landi a (28) yes yes cd na na yes cd yes yes fair fair lazar hl (45) yes yes cd na na yes cd yes yes fair fair lee m (46) yes yes na cd na yes cd yes yes fair fair liabeuf s(47) yes yes cd cd na yes cd yes yes fair fair liu b (48) yes yes na cd na yes cd yes yes fair fair lorenzo-villalba n(49) yes yes nr cd na yes cd yes yes fair fair loungani rs(50) yes yes nr cd na yes cd yes yes fair fair lodigiani c(34) yes yes cd cd na yes cd yes yes fair fair long b (51) yes yes cd cd na yes cd yes yes fair fair lopez m (52) yes yes cd cd na yes cd yes yes fair fair ma j (53) yes yes cd na na yes cd yes yes fair fair ma l (54) yes yes cd na na yes cd na yes fair fair mao l(43) yes yes cd na na yes cd na yes fair fair mauro v(55) yes yes na cd na yes cd yes yes fair fair mendoza-pinto c(56) yes yes nr cd na yes cd yes yes fair fair nobile b (57) yes yes cd cd na yes cd yes yes fair fair nogueira ms (29) yes yes cd cd na yes cd yes yes fair fair orsi fa(33) yes yes na cd na yes cd yes yes fair fair oudkerk m(58) yes yes na na na yes cd yes yes fair fair palmer k (59) yes yes na na na yes cd yes yes fair fair poggiali e (35) yes yes na cd na yes cd yes yes fair fair parry ah (60) yes yes na cd na yes cd yes yes fair fair patel vg (61) yes yes na na na yes cd na yes fair fair paul p (62) yes yes cd na na yes cd yes yes fair fair paybast s (42) yes yes cd na na yes cd yes yes fair fair pryce-roberts a(38) yes yes na cd na yes cd yes yes fai fair puntmann vo(37) yes yes na cd na yes cd yes yes fair fair rey jr (63) yes yes na cd na yes cd yes yes fair fair roche ja(64) yes yes cd cd na yes cd yes yes fair fair rosen rj(65) yes yes na na na yes cd yes yes fair fair saban-ruiz j (66) yes yes nr cd na yes cd yes yes fair fair sheraton m (39) yes yes cd cd na yes cd yes yes fair fair siguret v (67) yes yes cd cd na yes cd yes yes fair fair silingardi r (68) yes yes cd cd na yes cd yes yes fair fair silverman – chen lin da (69) yes yes cd na na yes cd yes yes fair fair na: not applicable; nih: national institutes of health; nr: not reported; cd: cannot determine *the nih quality assessment tool for case series studies contains nine questions: 1 = was the study question or objective clearly stated?, 2 = was the study population clearly and fully described, including a case definition?, 3 = were the cases consecutive?, 4 = were the subjects comparable?, 5 = was the intervention clearly described?, 6 = were the outcome measures clearly defined, 7 = was the length of follow-up adequate?, 8 = were the statistical methods well-described?, 9 = were the results well-described? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 10 table 1: quality ratings of included studies based on nih quality assessment (qa) tool for case series studies first author *question rating 1 2 3 4 5 6 7 8 9 # 1 # 2 singh y (23) yes yes na na na yes cd yes yes fair fair stevens dv (70) yes yes na na na yes cd yes yes fair fair strafella c (40) yes yes na na na yes cd yes yes fair fair tian d (71) yes yes na na na yes cd yes yes fair fair thomas w (72) yes yes cd cd na yes cd yes yes fair fair terpos e (73) yes yes nr cd na yes cd yes yes fair fair varatharaj a (41) yes yes na cd na yes cd yes yes fair fair varatharajah n (24) yes yes na cd na yes cd yes yes fair fair wagener f (10) yes yes cd cd na yes cd na yes fair fair wang x (6) yes yes na na na yes cd yes yes fair fair zhu h (74) yes yes cd na na yes cd yes yes fair fair abboud h (75) yes yes cd cd na yes cd yes yes fair fair khan s (76) yes yes cd cd na yes cd yes yes fair fair khandait h (77) yes yes cd cd na yes cd yes yes fair fair msigwa s s(78) yes yes na cd na yes cd yes yes fair fair sheikh a b (79) yes yes na cd na yes cd yes yes fair fair siripanthong b (80) yes yes na na na yes cd yes yes fair fair vonck k (81) yes yes cd na na yes cd yes yes fair fair wijeratne t (82) yes yes na na na yes cd yes yes fair fair yachou y (83) yes yes cd na na yes cd yes yes fair fair zaim s (84) yes yes na cd na yes cd yes yes fair fair na: not applicable; nih: national institutes of health; nr: not reported; cd: cannot determine *the nih quality assessment tool for case series studies contains nine questions: 1 = was the study question or objective clearly stated?, 2 = was the study population clearly and fully described, including a case definition?, 3 = were the cases consecutive?, 4 = were the subjects comparable?, 5 = was the intervention clearly described?, 6 = were the outcome measures clearly defined, 7 = was the length of follow-up adequate?, 8 = were the statistical methods well-described?, 9 = were the results well-described? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e14 figure 1: flow diagram of the selection process of articles identified. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 12 figure 2: frequency of identified late complications of covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e14 table 2: identified late complications of covid-19 id first author study type country study population late complications neurologic lung disease liver diseases heart damage thrombosis kidneydisease stroke 1 ali sepehrinezhad (21) perspective review iran patients with neurological complications p × × × × × × – 2 filatov a (22) case report usa 74-year-old male p × × × × × × encephalopathy 3 helms j (25) editorial france covid19 patients p × × × × × p – 4 heneka mt (2) review germany covid19 patients p × × × × × × – 5 kochi an (26) review italy covid19 patients × p × p × × p – 6 klok fa (27) casecontrol netherlands covid19 patients × × × × p × × – 7 klok fa (30) casecontrol netherlands covid19 patients × × × p p × p symptomatic acute pulmonary embolism (pe), myocardial infarction or systemic arterial embolism 8 klok fa(30) casecontrol netherlands covid19 patients admitted to the icu × × × p p × p pulmonary embolism, dvt, ischemic, systemic arterial embolism 9 kunutsor sk(44) letter to editor uk covid 19 patients × × p × × × × hypoproteinemia 10 landi a (28) letter to editor italy covid-19 patients admitted to icu × p × p p × p – 11 lazar hl (45) commentary usa covid19 patients admitted to the icu × p × × × × × – 12 lee m (46) letter to editor china covid 19 patients with a history of cardiovascular diseases × × × p × × × – 13 liabeuf s(47) cohort france hospitalized patients with laboratoryconfirmed covid-19 × p × × × p × gi damage, septic shock 14 liu b (48) authors reply china covid19 patients × p × × p × × – 15 lorenzovillalba n(49) case report france a patient hospitalized for covid-19 × p × × p × × parotiditis, cutaneous complications such as hemorrhagic bullae with intra-bullae blood clots and dissecting hematomas, isolated herpetiform lesions, petechial rash 16 loungani rs(50) review usa covid 19 patients × × × p × × p 17 lodigiani c(34) cohort italy covid19 patients admitted to hospital × × × p p × p acute coronary syndrome (acs)/myocardial infarction (mi),overt disseminated intravascular coagulation (dic) 18 long b (51) cohort usa covid19 patients × p × p p × × systematic inflammation, myocardial injury, acute myocardial infarction, dysrhythmias, 19 lopez m (52) review usa covid19 patients p p p p p × p psychological distress 20 ma j (53) letter to editor china three critically ill patients with coronavirus disease 2019 (covid-19) p × × × p p p multiple organ dysfunction syndrome, dry gangrene, multiple cerebral infarction, refractory disseminated intravascular coagulation (dic) and pneumothorax 21 ma l (54) review china covid19 patients × p × p × × p pneumonia, persistent hypotension 22 mao l(43) research article china hospitalized patients with coronavirus disease 2019 p p × × × × × – 23 mauro v(55) point of view italy covid19 patients × × p × × × × – dvt: deep vein thrombosis; gi: gastrointestinal; pte: pulmonary thromboembolism; dic: disseminated intravascular coagulation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sa. seyedalinaghi et al. 14 table 2: identified late complications of covid-19 id first author study type country study population late complications neurologic lung disease liver diseases heart damage thrombosis kidneydisease stroke 24 mendozapinto c(56) letter to editor mexico covid19 patients × × × p p p × elevated d-dimer, and coagulation abnormalities, catastrophic antiphospholipid syndrome (caps), multiple small vessel occlusions, multiorgan system failure 25 nobile b (57) letter to editor france covid19 patients using cloripramine p p × × × × p psychological distress, ischemic attacks, leading to brain inflammation and lesions 26 nogueira ms (29) review ireland covid19 patients × p × × × × × pneumonia, acute respiratory distress syndrome (ards) and lymphadenopathy 27 orsi fa(33) review brazil hospitalizedcovid19 patients × p × × p × × septic shock or multiple organ dysfunction, ards, hypercoagulability 28 oudkerk m(58) special report netherlands covid-19 patients × p × p p p × gi damage, vascular endothelial damage 29 palmer k (59) review italy covid-19 patients with noncommunicable disease (ncd) × p × p p × p psychological distress, exacerbated chronic ncd conditions (e.g., asthma, chronic obstructive, congestive cardiac failure) 30 poggiali e (35) case reports italy an 82-year-old woman, a 64-year-old man × p × × p × × venous thromboembolism, deep pulmonary embolism 31 parry ah (60) letter to editor india covid-19 patients with pneumonia × p × × p × × diffuse alveolar damage, acute respiratory distress syndrome, pulmonary vascular damage, pte 32 patel vg (61) letter to editorcohort usa covid-19 patients with prostate cancer × p × × × × × – 33 paul p (62) letter to editor india covid-19 patients × p × p × × × ards, pneumonia, multiple organ failure, infective myocarditis 34 paybast s (42) review iran covid-19 patients p p × × × p p gi disease, intracranial hemorrhage, hyposmia and hypogeusia, disorientation, third nerve palsy 35 pryce-roberts a(38) review uk covid-19 patients p × × × × × p dysgeusia, hyposmia, disorientation, encephalitis, meningoencephalitis, and encephalopathy 36 puntmann vo(37) clinical trial germany patients recently recovered from covid-19 × × × p × × × – 37 rey jr (63) letter to editor spain patients attended due to covid-19 × p × p p × p acute coronary syndrome 38 roche ja(64) hypothesis usa covid 19 patients with deregulated bk signaling × p × × × × × – 39 rosen rj(65) letter to editor usa × × × × p × p – 40 saban-ruiz j (66) review spain cardiometabolic health/medicine × × × p × × p – 41 sheraton m (39) review usa patients with neurological complications p × × × × × × guillain-barre syndrome 42 siguret v (67) letter to the editor france thrombotic complications in critically ill covid-19 × × × × p × p – 43 silingardi r (68) letter to the editor italy acute limb ischemia in covid-19 patients × × × × p × × acute limb ischemia-pulmonary embolism-aortic floating thrombus 44 silverman – chen lin da (69) review usa covid-19 patients × p × × × × × – dvt: deep vein thrombosis; gi: gastrointestinal; pte: pulmonary thromboembolism; dic: disseminated intravascular coagulation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2021; 9(1): e14 table 2: identified late complications of covid-19 id first author study type country study population late complications neurologic lung disease liver diseases heart damage thrombosis kidneydisease stroke 45 singh y (23) letter to the editor india cellular metabolism mediated complications in covid-19 infection p p × p × p p cell death triggered by ferroptotic stress 46 stevens dv (70) case-study usa complications of orbital emphysema in a covid-19 patient × p × × p × × – 47 strafella c (40) analytic italy analysis of ace2 genetic variability among populations p p × p × p × sepsis 48 tian d (71) review china covid-19 patients × × p × × × × – 49 thomas w (72) letter to the editor united kingdom thrombotic complication of a patient with covid-19 × × × × p × p – 50 terpos e (73) review greece hematologic complications in covid-19 patients × × × p p × × – 51 varatharaj a (41) casecontrol uk covid-19 patients p × × × × × p thrombotic complication of a patient with covid-19 52 varatharajah n (24) letter to the editor usa microthrombotic complications of patients with covid-19 × p × × p × × hematologic complications in covid-19 patients 53 wagener f (10) viewpoint netherlands critically ill covid-19 patients × p × × × × × coagulation abnormality 54 wang x (6) research article china chronic diseases among patients with covid-19 × × p p p p × – 55 zhu h (74) review usa patients with covid-19 × p × p × × × coagulopathy-dic 56 abboud h (75) review morocco patients with covid-19 p × × × × × × – 57 khan s (76) review malaysia patients with covid-19 × × × × p × × – 58 khandait h (77) research article india patients with covid-19 × p × p p × p coagulopathy-dic-pulmonary embolism-deep vein thrombosis 59 msigwa s s(78) review china patients with covid-19 p × × × × × × – 60 sheikh a b (79) case-report usa 56-year-old man with covid-19 × × × p p × × – 61 siripanthong b (80) review uk patients with covid-19 × × × p × × × myocarditis 62 vonck k (81) review belgium patients with covid-19 p × × × × × × central nervous system (cns) manifestations [dizziness, headache, impaired, consciousness, acute cerebrovascular disease (cvd), ataxia and seizure], cranial and peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment and neuropathy), and skeletal muscular injury manifestations 63 wijeratne t (82) review australia patients with covid-19 p × × × × × p acute ischemic stroke 64 yachou y (83) review russia patients with covid-19 p × × × × × × – 65 zaim s (84) review uk patients with covid-19 p p p p × p × dic dvt: deep vein thrombosis; gi: gastrointestinal; pte: pulmonary thromboembolism; dic: disseminated intravascular coagulation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e24 or i g i n a l re s e a rc h predictive factors of survival and 6-month favorable outcome of very severe head trauma patients; a historical cohort study karin vathanalaoha1, thakul oearsakul1, thara tunthanathip1∗ 1. neurosurgical unit, department of surgery, faculty of medicine, songklanagarind hospital prince of songkla university, hat yai, songkhla, thailand. received: march 2016; accepted: july 2016; published online: 10 january 2017 abstract: introduction: very severe head trauma cases, defined as glasgow coma scale (gcs) scores of less than 6, have a higher mortality rate and poorer outcome. the purpose of this study was to recognize factors associated with survival and 6-month favorable outcome of very severe head trauma patients presenting to emergency department. methods: in this historical cohort study, the authors retrospectively reviewed medical records of head trauma patients who were admitted to the emergency department with post-resuscitation gcs scores of less than 6. both univariate and multivariate analyses were used to test the association between various parameters with survival and 6-month outcome. results: 103 cases with the mean age of 39 ± 16.5 years were studied (80% male). the overall survival rate was 41.7% and the rate of 6-month favorable outcome was 28.2%. in multivariate analysis, brisk pupil light reaction on admission and patent basal cistern on brain computed tomography (ct) scan were significant factors associated with both survival (or 5.20, 95% ci 1.57-17.246, p = 0.007 and or 3.65, 95% ci 1.22-10.91, p=0.02 respectively) and favorable outcome (or 4.07, 95% ci 1.35-12.24, p=0.01 and or 3.54, 95% ci 1.22-10.26, p 0.02), respectively. conclusion: based on the results of present study, the survival rate of patients with very severe head trauma (gcs < 6) was 41.7%. the strong predictors of survival and 6-month favorable outcome of these patients were brisk pupillary reactivity and patent cistern on brain ct scan. it seems that very severe head trauma patients still have a reasonable chance to survive and aggressive management should be continued. keywords: glasgow coma scale; head injuries, closed; prognosis; treatment outcome; outcome assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: vathanalaoha k, oearsakul th, tunthanathip th. predictive factors of survival and 6-month favorable outcome of very severe head trauma patients; a historical cohort study. emergency. 2017; 5 (1): e24. 1. introduction accidents are among the top three causes of death in thailand. the incidence rate of traffic accident mortality in thailand was 21.61-23.16 per 100,000 people and the trend of mortality gradually increased between 2010 and 2013. pheunpathom et al. reported that 15.8-29% of trauma patients in the emergency room had head injuries and the most common mechanism of head injury was road traffic accidents (1). generally, the severity of head injury was categorized ∗corresponding author: thara tunthanathip; neurosurgical unit, department of surgery, faculty of medicine, hatyai, songkhla, thailand, 90112. phone: +66-85-8203334 fax: +66-74-429384 email: tsus4@hotmail.com, tthara@medicine.psu.ac.th into 3 categories using glasgow coma scale (gcs) scores, mild head injury (gcs scores 15-13), moderate head injury (gcs scores 12-9) and severe head injury (gcs scores 8-3). gennarelli et al. reported that patients with gcs scores of 3 to 5 had a higher mortality rate than patients with gcs scores of 6 to 8 (2). very severe head injury was defined as cases of head trauma with gcs scores of less than 6 (3) because the highest mortality rates have been reported 42-87.5% in this group (2-4). these patients were subject to limited use of resources and even treatment in several facilities (3, 5-7). a small number of studies have involved patients with gcs scores <6 and have reported that, <60 years of age, adequate spontaneous respiration, brisk pupillary reactivity, increase in gcs score by at least 2 within 24 hours of admission and the appearance of basal cistern on first brain computed tomography (ct) scan were significant predictors of outcome in very sethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. vathanalaoha et al. 2 vere head injury (3-8). the purpose of this study was to recognize factors associated with survival and 6-month favorable outcome of very severe head trauma patients presenting to emergency department. 2. methods 2.1. study design in this historical cohort study, the authors retrospectively reviewed computer-based medical records of all head trauma patients who were admitted to songklanagarind hospital between january 1, 2008 and march 31, 2011. songklanakarind hospital is the tertiary care center serving both direct transfers from the accident scene and transfer from 14 provinces in the southern region of thailand (1). the authors adhered to all principles of helsinki declaration and confidentiality of patient records during the study period. the human research ethics committee of the faculty of medicine, songklanagarind hospital, prince of songkla university approved the study. 2.2. participants the patients who had post-resuscitation gcs scores of less than 6, which persisted for at least 6 hours were selected to participate in the present study. however, patients with penetrating mechanism and pediatric cases were excluded. documented data including the demographic data, mechanism of injury, physical examination, neurological examination, neurological imaging findings, types of intracranial hematoma, treatments, and types of surgery were gathered from computer-based medical records by a neurosurgeon. additionally, the 6-month outcome of injury was documented by telephone call with patient/caregiver. also, brain ct scans of all patients were assessed regarding intracranial lesions and the appearance of the basal cisterns according to the marshall classification (9) by a neuro-radiologist. 2.3. definitions the pupillary reaction to light on admission was classified into 2 groups; the poor pupils group included patients who had sluggish/no reactivity to light on both sides and with any size of pupils, while the brisk pupil/pupils group consisted of those who had at least one side of pupil to briskly response to light. glasgow outcome scale (gos) was used for outcome measurements. gos consists of good recovery (gr), moderated disability (mr), severe disability (sd), vegetative stage (vs), and death (d) (10). finally, based on gos, patients were dichotomized into 2 groups. the favorable outcome group included gr and mr, while the unfavorable outcome group consisted of all others. the marshall classification categorized brain ct scans into 6 groups using some intracranial features. this system is composed of diffuse injury i (no visible intracranial pathology), diffuse injury ii (cistern are present with midline shift < 5 mm, and no high/mixed density lesion > 25 cm3), diffuse injury iii (basal cisterns compressed or absent with midline shift 0-5 mm, and no high/mixed density lesion > 25 cm3), diffuse injury iv (midline shift > 5 mm, no high/mixed density lesion > 25 cm3 ), evacuated mass (v ) (any lesion surgically evaluated), and non-evacuated mass lesion (vi) (no high/mixed density lesion > 25 cm3 and not surgically evacuated) (9). motor response is one of the three tests in glasgow coma scale. the motor response is comprised of 6 grades: obeys commands (m6), localizes to pain (m5), withdrawal from pain (m4), decorticate posturing (m3), decelerate posturing (m2), and no motor response (m1) (11). 2.4. statistical analysis all analyses were performed by the r and epical program 2.9.1 version (12).mean and standard deviation were calculated for descriptive purposes. the chi-square test and fisher’s extract test were performed for comparison of dichotomous parameters between groups. univariate logistic regression analysis was used to compare the odds of several parameters to predict the outcome and survival. finally, multivariate logistic regression analysis was used to adjust the odds to predict outcome and survival of the patients. a p<0.05 was considered statistically significant. 3. results: 3.1. demographic data 103 cases with the mean age of 39 ± 16.5 years (range: 16.582) were studied (80% male). table 1 shows the demographic data and baseline characteristics of the patients. two-third of patients had gcs 3. the median time of pre-hospital transfer was 30 minutes (iqr 20, 90) and pre-hospital hypoxia and hypotension were observed in 17.5% and 44.7%, respectively. seventy-nine individuals (76.7%) were in poor pupil groups. the median time of injury to brain ct scan was 77.5 minutes (iqr 41.2). the most common brain ct scan findings were subdural hematomas (75.7%), calvarial skull fracture (58.3%), basal skull fracture (59.2%), and basal cistern obliteration (56.3%). two-third of patients (65.4%) were admitted to the intensive care unit (icu) and the remainder were admitted to the trauma (28.2%) or neurosurgical units with intensive care (6.4%). during acute hospitalization, the median length of hospital stay was 9 days (iqr 2, 29 days). forty-seven individuals (45.6%) required emergency surgery and decompressive craniotomy with clot removal was the most common surgical procedure that the patients underwent. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e24 figure 1: classification tree for predictive variables associated with survival. * the number of patients was 101 patients because 2 patients with severe periborbital swelling on both sides could not have their pupils evaluated. abbrevation; na: not availiable. 3.2. survival rate and outcome the overall survival rate in the present study was 41.7%. twenty-seven patients (26.2%) observed desirable recovery after acute hospitalization and 2 patients recovered to a favorable group by 6 months after injury. on the other side, sixteen patients (15.6%) were dependent and no patient died during the 6-month follow-up. 3.3. factors associated with survival rate table 2 shows the univariate analysis to identify factors associated with survival rate. the authors found that brisk pupillary reactivity, hypotension on admission, hydrocephalus, patent basal cistern, marshall classification, and performing operation were factors that associated with survival in univariate analysis. table 3 shows the results of multivariate analysis in this regard. brisk pupillary reactivity and patent basal cistern on brain ct scan were factors that significantly associated with survival. 3.4. survival rate and outcome table 4 shows the univariate analysis to identify factors associated with 6-month favorable outcome. brisk response to light of pupil or pupils, epidural hematoma thickness less than 1.5 cm, patent basal cistern and marshall classification were factors associated with 6-month favorable outcome in univariate analysis. table 5 reveals the results of multivariate logistic analysis in this regard. accordingly, brisk pupillary reactivity and patent basal cistern on brain ct scan had a statistically significant association with 6-month favorable outcome. 3.5. survival classification tree figure 1 describes the survival chances of very severe head trauma patients in a classification tree. a higher survival rate was observed in the group with gcs scores of 5 compared to patients with gcs scores of 3-4 when they had similar poor pupil response and obliterated cistern on brain ct scan. 4. discussion: based on the results of present study, the survival rate of patients with very severe head trauma (gcs < 6) was 41.7%. the strong predictors of survival and 6-month favorable outcome of these patients were brisk pupillary reactivity and patent cistern on brain ct scans. the use of gcs is a universal method to classify the severity of patients with head injury; patients with gcs scores of 3-4-5 have limited survivability. these patients have poor prognosis. prior studies reported an overall mortality of 42-87.5% (2-6). in literature, clinical characteristics and imaging findings have been shown to correlate with outcome in the very severe group. nevertheless, limited numbers of studies have examined the outcomes of patients with gcs scores of 3-5. bilateral fixed dilated pupils (bfdp) are a significant predictor in concordance with several studies (4, 13-16). lieberman et al. studied 137 trauma patients with a gcs score of 3. mortality was 100% in the bfdp group whereas the non-bfdp group had 77% mortality (14). sakas et al. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. vathanalaoha et al. 4 table 1: baseline characteristics of studied patients characteristic n (%) sex male 83 (80.6) female 20 (19.4) age (year) 16-20 11 (10.7) 21-40 50 (48.5) 41-60 31 (30.1) >60 11 (10.7) underlying disease none 83 (80.6) hypertension 10 (9.9) neurological 1 (1.0) gastro enteric 1 (1.0) respiratory 1 (1.0) other 5 (4.9) drug none 92 (92.0) unidentified drug 3 (3.0) aspirin 1 (1.0) other 4 (4.0) mechanism of trauma falling 7 (6.8) vehicle accident 8 (7.8) motorcycle accident 78 (75.7) pedestrians 3 (2.9) body assault 2 (1.9) other 5 (4.9) glasgow coma scale 3 64 (62.1) 4 28 (27.2) 5 11 (10.7) pupillary reactivity* poor pupils 79 (76.7) brisk pupil/pupils 22 (21.8) motor response m1 68 (66.0) m2 24 (23.3) m3 11 (10.7) hypoxia episode 18 (17.5) hypotension episode 46 (44.7) calvarial skull fracture none 42 (40.8) linear 57 (55.3) depressed 3 (2.9) compound 1 (1.0) basal skull fracture 60 (58.3) intracranial findings cerebral contusion 56 (54.4) intracerebral hemorrhage 48 (46.6) subdural hemorrhage 78 (75.7) epidural hemorrhage 19 (18.4) intraventricular hemorrhage 20 (19.4) hydrocephalus 17 (16.5) brainstem hemorrhage 4 (3.9) appearance of basal cistern patent 44 (43.1) obliteration 58 (56.3) table 1: baseline characteristics of studied patients (continued) characteristic n (%) marshall classification grade i 5 (4.9) grade ii 19 (18.4) grade iii 32 (31.1) grade iv 1 (1) evacuated mass lesion 39 (37.9) non-evacuated mass lesion 7 (6.8) operation no 56 (54.4) craniotomy with clot removal 8 (7.8) decompressive craniotomy with clot removal 33 (32.0) icp monitoring 6 (5.8) gos at discharge dead 60 (58.3) vegetative state 12 (11.7) severe disability 4 (3.9) moderate disability 16 (15.5) good recovery 11 (10.7) gos at 6 months dead 60 (58.3) vegetative state 10 (9.7) severe disability 4 (3.9) moderate disability 9 (8.7) good recovery 20 (19.7) outcome at 6 months unfavorable (gos 1-3) 74 (71.8) favorable (gos 4-5) 29 (28.2) * 2 patients could not be categorized into groups because of periorbital swelling on both sides. gos: glasgow outcome scale. studied 40 trauma patients with bfdp. mortality was 100% if patients presented any of the following features: surgery 6 or more hours after bilateral loss of pupil reactivity, age more than 65 years, or absent motor response (15). tien et al. compared trauma patients with a gcs of 3 and bfdp with patients with a gcs score of 3 and reactive pupils. mortality was 100% versus 42%; hemodynamic instability, midline shift, and herniation were observed in the bfdp patients (4). generally, the neuronal pathway of pupillary light reflex is located in the intrinsic brainstem. light reflex is conducted by optic tract fibers, which synapse in the pretectal area. the pretectal neurons synapse to the edinger-westphal complex. finally, the ciliary nerve serves pupillary constrictor responses (16). pupillary dilatation and no response to light are caused by a compressed ipsilateral oculomotor nerve and brainstem ischemia. ritter et al. reported that brain stem blood flow (bbf) was 30.5+/-16.8 ml/100 g/min in bfdp patients whereas it was 43.8+/-18.7 ml/100 g/min (p< 0.001)(17). therefore, the present study has quite a different classification in pupillary reactivity. previous studies assessed light reflex of both pupils. we hypothesized that brisk reactivity of either one pupil or both this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e24 table 2: associated factors of 6 months survival based on univariate analysis factor death survival or (95%ci) p age (year) < 55 47 (78.3) 37 (86.0) ref 0.32 ≥ 55 13 (21.7) 6 (14.0) 0.58 (0.20-1.69) sex male 49 (81.7) 34 (79.1) ref 0.74 female 11 (18.3) 9 (20.9) 1.17 (0.44-3.15) glasgow coma scale 3 40 (66.7) 24 (55.8) ref 4 16 (26.7) 12 (27.9) 1.25 (0.50-3.08) 0.26 5 4 (6.7) 7 (16.3) 2.91 (0.77-11.01) pupillary reactivity poor pupils 53 (89.8) 26 (61.9) ref 0.001‡ brisk pupil/pupils 6 (10.2) 16 (38.1) 6.16 (2.22-17.07) motor response m1 42 (70.0) 26 (60.5) ref m2 14 (23.3) 10 (23.3) 1.15 (0.44-2.97) 0.28 m3 4 (6.7) 7 (16.3) 2.82 (0.75-10.60) hypoxia no 47 (78.3) 38 (88.4) ref 0.18 yes 13 (21.7) 5 (11.6) 0.49 (0.15-1.43) hypotension no 27 (45.0) 30 (69.8) ref 0.01‡ yes 33 (55.0) 13 (30.2) 0.33 (0.15-0.81) intracerebral hemorrhage (ich) no 32 (53.3) 22 (52.4) ref 0.92 yes 28 (46.7) 20 (47.6) 1.03 (0.42-2.28) contusion no 29 (48.3) 18 (41.9) ref 0.51 yes 31 (51.7) 25 (58.1) 1.29 (0.59-2.86) posterior fossa ich no 59 (98.3) 40 (95.2) ref 0.36 yes 1 (1.7) 2 (4.8) 1.26 (0.11-14.54) subdural hematoma thickness (cm) < 1 41(68.3) 30 (71.4) ref 0.73 ≥ 1 19 (31.7) 12 (28.6) 0.86 (0.36-2.04) epidural hematoma thickness (cm) < 1.5 58 (96.7) 38 (90.5) ref 0.19 ≥ 1.5 2 (3.3) 4 (9.5) 3.05 (0.53-17.49) intraventricular hemorrhage no 45 (75.0) 37 (88.1) ref 0.10 yes 15 (25.0) 5 (11.9) 0.40 (0.13-1.22) hydrocephalus no 46 (76.7) 39 (92.9) ref 0.03‡ yes 14 (23.3) 3 (7.1) 0.23 (0.68-0.94) midline shift (mm) <5 39 (66.1) 27 (64.3) ref 0.85 ≥ 5 20 (33.9) 15 (35.7) 1.08 (0.42-2.48) basal cistern appearance obliteration 40 (66.7) 18 (42.9) ref 0.01‡ patent 20 (33.3) 24 (47.1) 2.66 (1.18-6.01) * p value of chi-square test, † p value of fisher’s exact test, ‡ statistical significant. or: odds ratio, ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. vathanalaoha et al. 6 table 2: associated factors of 6 months survival based on univariate analysis (continued) factor death survival or (95%ci) p brainstem hemorrhage no 58 (96.7) 40 (95.2) ref 1.45 yes 2 (3.3) 2 (4.8) 1.45 (0.19-10.72) operation no 39 (65.0) 17 (39.5) ref 0.01‡ yes 21 (35.0) 26 (60.5) 2.84 (1.24-6.28) * p value of chi-square test, † p value of fisher’s exact test, ‡ statistical significant. or: odds ratio, ci: confidence interval. table 3: associated factors of 6 months survival based on multivariate analysis variable or (95%ci) p pupillary reactivity poor pupils ref 0.007 brisk pupil/pupils 5.20 (1.57-17.26) basal cistern appearance obliteration ref 0.02 patent 3.65 (1.22-10.91) hypotension no ref 0.63 yes 1.31 (0.42-4.07) hydrocephalus no ref 0.82 yes 1.18 (0.26-5.29) operation no ref 0.36 yes 0.58 (0.18-1.86) or: odds ratio; ci: confident interval. pupils is sufficient to indicate the function of the brainstem. in addition, we found that only one pupil showing good response to light directly related to the chance of survival and favorable outcome. in our study, another factor, the appearance of basal cistern on brain ct scan, has been determined to correlate with survival and outcome. absence of obliterated basal cistern had an independent association with survival and good outcome. toutant et al. studied 218 patients with severe head injury and found a strong relationship between mortality rate and death. in detail, death rate in patients with compressed cisterns was approximately twice as high compared with normal cistern (39% and 22%, respectively) (18). on the other hand, mauritz et al. investigated outcomes of very severe head injury cases that had a gcs score of 3. the opening cistern on the first brain ct scan was one potential predictor of survival and good functional recovery (13). the strength of the present study includes more detailed assessment of statistically significant factors affecting survival such as pupillary reactivity. however, the present study has limitations including retrospective study design and assessment of early outcome. firstly, the quality of data and bias may be affected by study design. the second limitation is only assessing early outcome. long-term outcome is an uncommon aspect to assess in these patients. interestingly, late outcome assessment of survivors who had very severe head injuries in other studies has shown that physical and psychological impairment remains in many cases (19). for studying clinical implications, we suggest a prospective study design for better data quality. long-term outcome assessment should also be considered in the future. it seems that very severe head trauma patients still have a reasonable chance to survive and management should be continued. the results of this study may guide physicians to decide whether to continue treatment in patients or not. 5. conclusion: based on the results of present study, the survival rate of patients with very severe head trauma (gcs < 6) was 41.7%. the strong predictors of survival and 6-month favorable outcome of these patients were brisk pupillary reactivity and patent cistern on brain ct scan. it seems that very severe head trauma patients still have a reasonable chance to survive and management should be continued. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e24 table 4: associated factors of 6 months favorable outcome based on univariate analysis factor unfavorable favorable or (95%ci) p age (year) < 55 58 (78.4) 26 (89.7) ref 0.26 † ≥ 55 16 (21.6) 3 (10.3) 0.41 (0.11-1.56) sex male 58 (78.4) 25 (86.2) ref 0.36 female 16 (21.6) 4 (13.8) 0.58 (0.17-1.91) gcs 3 48 (64.9) 16 (55.2) ref 4 19 (25.7) 9 (31.0) 1.42 (0.53-3.76) 0.63 5 7 (9.5) 4 (13.8) 1.71 (0.44-6.62) pupillary reactivity poor pupils 64 (87.7) 15 (53.6) ref 0.001‡ brisk pupil/pupils 9 (12.3) 13 (46.4) 6.2 (2.22-17.07) motor response m1 51 (68.9) 17 (58.6) ref m2 16 (21.6) 8 (27.6) 1.50 (0.54-4.12) 0.60 m3 7 (9.5) 4 (13.8) 1.71 0.44-6.58) hypoxia no 60 (81.1) 25 (86.2) ref 0.53 yes 14 (18.9) 4 (13.8) 0.68 (0.25-2.28) hypotension no 39 (52.7) 18 (62.1) ref 0.59 yes 35 (47.3) 11 (37.9) 0.68 (0.28-1.63) intracranial hemorrhage (ich) no 41 (56.2) 13 (44.8) ref 0.30 yes 32 (43.8) 16 (55.2) 1.57 (0.66-3.74) contusion no 36 (48.6) 11 (37.9) ref 0.32 yes 38 (51.4) 18 (62.1) 1.55 (0.64-3.72) posterior fossa ich no 71 (97.3) 28 (96.6) ref 0.84* yes 2 (2.7) 1 (3.4) 1.3 (0.11-14.54) subdural hemorrhage thickness (cm) < 1 49 (66.2) 22 (78.6) ref 0.22 ≥ 1 25 (33.8) 6 (21.4) 0.5 (0.19-1.48) epidural hemorrhage thickness (cm) < 1.5 72 (97.3) 24 (85.7) ref 0.02‡ ≥ 1.5 2 (2.7) 4 (14.3) 6.0 (1.03-34.84) intraventricular hemorrhage no 57 (77.0) 25 (89.3) ref 0.16 yes 17 (23.0) 3 (10.7) 0.40 (0.10-1.49) hydrocephalus no 60 (81.1) 25 (89.3) ref 0.18 yes 14 (18.9) 3 (10.7) 0.51 (0.13-1.94) midline shift (mm) <5 46 (62.2) 22 (75.9) ref 0.18 ≥ 5 28 (37.8) 7 (24.1) 0.52 (0.19-1.38) basal cistern appearance obliteration 49 (66.2) 9 (32.1) ref 0.02‡ patent 25 (33.8) 19 (67.9) 4.1 (1.6-10.5) * p value of chi-square test, † p value of fisher’s exact test, ‡ statistical significant. or: odds ratio, ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. vathanalaoha et al. 8 table 4: associated factors of 6 months favorable outcome based on univariate analysis (continued) factor unfavorable favorable or (95%ci) p brainstem hemorrhage no 71 (95.9) 27 (96.4) ref 0.91 yes 3 (4.1) 1 (3.6) 0.87 (0.08-8.79) operation no 40 (54.1) 16 (55.2) ref 0.98 yes 34 (45.9) 13 (44.8) 0.95 (0.40-2.26) *p value of chi-square test, † p value of fisher’s exact test, ‡ statistical significant. or: odds ratio, ci: confidence interval. table 5: associated factors of 6 months favorable outcome based on multivariate analysis variable or (95%ci) p value pupillary reactivity poor pupils ref 0.01 brisk pupil/pupils 4.07(1.35-12.24) basal cistern appearance obliteration ref 0.02 patent 3.54 (1.22-10.26) epidural hematoma thickness (cm) <1.5 ref 0.13 ≥ 1.5 4.46 (0.64-31.15) or: odds ratio; ci: confident interval. 6. appendix 6.1. acknowledgements the authors would like to offer their special thanks to dr. nuttha sanghan for brain ct scan assessments. 6.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interest none. 6.4. funding and supports: the authors declare that they have no affiliations with or 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open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references archives of academic emergency medicine. 2023; 11(1): e16 or i g i n a l re s e a rc h associated factors of in-hospital mortality among intubated older adults in emergency department; a crosssectional study mohd idzwan zakaria1, norhadila che manshor2, tan maw pin1∗ 1. academic trauma and emergency unit, faculty of medicine, university of malaya, kuala lumpur, malaysia. 2. geriatric unit, department of medicine, faculty of medicine, university of malaya, kuala lumpur, malaysia. received: november 2022; accepted: december 2022; published online: 3 january 2023 abstract: introduction: a decision-making guideline on when to intubate an older person based on predictors of intubation outcome would be extremely beneficial. this study aimed to identify the associated factors that could predict the outcomes of endotracheal intubation among older adults in the emergency department (ed). methods: in this retrospective cross-sectional study, patients aged ≥65 years intubated at the ed of university of malaya medical centre, kuala lumpur, malaysia, from 2015 to 2019 were studied. the association between age, gender, place of inhabitation, identification of seniors at risk (isar) score for frailty, charlson comorbidity index (cci), acute physiology and chronic health evaluation-ii (apache-ii) score, indication for intubation, and diagnosis on admission with in-hospital mortality (primary outcome) and duration of ventilation, and length of stay (secondary outcomes) were evaluated using univariate analysis and cox’s regression survival analysis. results: 889 cases aged 65 years and above were studied (61.5% male). the rate of in-hospital mortality was 71.4%. there was a significant association between age (p < 0.001), nursing home residency (p = 0.008), cci≥ 5 (p = 0.001), apache-ii (p < 0.001), pre-intubation glasgow coma scale (gcs) (p < 0.001), cardiac arrest as indication of intubation (p < 0.001), diagnosis on admission (p < 0.001), length of stay (p < 0.001), and length of ventilation (p = 0.003) and in-hospital mortality. age ≥ 85 years (hr= 1.270; 95%ci=1.074 to 1.502) and 75 to 84 years (hr=1.642; 95%ci=1.167 to 2.076), cardiac arrest as indication of intubation (hr: 1.882; 95% ci: 1.554 – 2.279), and apache-ii scores 25 – 34 (hr: 1.423; 95% ci: 1.171 1.730) and ≥ 35 (hr: 1.789; 95%ci: 1.418 2.256) were amongst the independent predictive factors of in-hospital mortality. conclusion: nearly three out of four individuals aged ≥65 years intubated at the ed died during the same admission. older age, cardiac arrest as indication of intubation, and apache-ii score were independent predictors of in-hospital mortality. keywords:aged; intubation; emergency service, hospital; respiration, artificial cite this article as: idzwan zakaria m, che manshor n, maw pin t. associated factors of in-hospital mortality among intubated older adults in emergency department; a cross-sectional study. arch acad emerg med. 2023; 11(1): e16. https://doi.org/10.22037/aaem.v11i1.1613. 1. introduction population ageing is occurring faster in lowto middleincome countries than high-income countries (1). in 2020, the number of older adults aged 65 years and above has increased to 7.0% of the total malaysian population, compared to 6.7% in 2019. by 2030, older adults are expected to make up more than 15% of the malaysian population (2). this demographic shift has been attributed to improved nutrition and sanitation, increasing life expectancy, and declining fer∗corresponding author: tan maw pin; geriatric unit, department of medicine, faculty of medicine, university of malaya, 50603 kuala lumpur, malaysia. email: mptan@ummc.edu.my, tel: +60163328600, fax: +60379492030, orcid: https://orcid.org/0000-0002-3400-8540. tility rates (3). advancements in medical science have led to improved critical care and surgical management. while critical care management regularly involves ventilatory support, such lifesustaining treatment in some individuals, particularly those in the older age group, may not necessarily lead to survival benefits (4). the decision whether to perform endotracheal intubation and artificial ventilation among older adults presenting with respiratory compromise in the emergency department (ed) is highly challenging. a retrospective cohort study by ouchi et al. suggested that one in three older adults intubated in the emergency department died in hospital (5). a study by foerch et al. mentioned that a quarter of intubated older stroke patients survived with good neurological outcome and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. idzwan zakaria et al. 2 reasonable quality of life (6). in a cross-sectional stratified random national survey, steinhouser et al. stated that more than 70% of older adults would choose quality of life above longevity (7). despite this, the intubation rate for critically ill older adults has increased by 30% from 2001 to 2011 and further doubled by 2020 (8). a decision-making guideline on when to intubate an older person based on predictors of intubation outcome would be extremely beneficial. therefore, this study aimed to evaluate the in-hospital mortality rate and its associated factors among older adults who received endotracheal intubation and ventilation at the ed. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on patients aged ≥65 years intubated at the ed of university of malaya medical centre (ummc), kuala lumpur, malaysia, from 2015 to 2019. the association between age, gender, place of inhabitation, identification of seniors at risk (isar) score for frailty, charlson comorbidity index (cci), acute physiology and chronic health evaluation-ii (apache-ii) score, indication for intubation, and diagnosis on admission with in-hospital mortality, duration of ventilation, and length of stay were evaluated. the ummc is a large teaching hospital with a total of 1100 beds. it receives 1.1 million visits annually with a 70-75% bed occupancy rate. the ed itself receives 25,000 older patients a year. ethical approval was obtained from the university of malaya medical center medical research ethics committee (mrec id no: 2020224-8310). the researchers adhered to the confidentiality of patients’ profiles and ethical considerations in biomedical research. 2.2. participants all patients aged 65 years and above attending the ed who received endotracheal intubation were identified from the hospital electronic medical records (emr) using the icd-10 procedural code for "insertion of endotracheal airway into trachea, via natural or artificial opening” and included in the study. those intubated outside the hospital, before arrival to hospital, and in the hospital ward were excluded. the list obtained was cross-checked with the medical records department. 2.3. data gathering data was extracted from the emr system using a standardized data collection document. information on age (9), gender, place of inhabitation (home, nursing home or others) (10), the identification of seniors at risk (isar) score for frailty (11), the charlson comorbidity index (cci) on admission (12), the acute physiology and chronic health evaluation-ii (apache-ii) score (13, 14), the glasgow coma scale (gcs) before intubation (15), indications for intubation, and diagnosis on admission (16-18), was retrieved. the isar is a six-item tool, which quantifies frailty using commonly measured variables in the ed (19). the responses are dichotomized as “yes” or “no”, and for each “yes” answer one point is allocated. those with a score ≥2 out of 6 were considered “at risk” of adverse outcomes. the charlson comorbidity index (cci) estimates the risk of death and is calculated by adding up weighed scores assigned to its 19 items, which are then summed up to a total score that ranges from 0–33. a total score of ≥5 was considered to show high risk of death (20). the apache-ii score assigns scores of 0-4 to 11 physiological measurements, including temperature, blood pressure, heart rate, respiratory rate, arterial ph, arterial oxygen saturation, serum sodium, serum potassium, serum creatinine, hematocrit, and white cell count, in addition to 0-6 to age and 2 or 5 for chronic health points (21). the gcs score is added to the sum of scores to obtain a maximal total score of 71. a total apache-ii score of ≥ 35 indicates a mortality risk of 80%. 2.4. outcomes the primary outcome was in-hospital mortality, and the secondary outcomes were the duration of ventilation, and length of hospital stay. the date of death was obtained through the hospital emr. 2.5. statistical analysis data analysis was carried out with the statistical package for social sciences software (spss, chicago, il, usa) version 22.0. the univariate association between each potential predictor and the primary outcome was analyzed using the chisquare test. the cox’s proportional hazards regression was used to develop a predictor model for time to hospital death. hazard ratios (hr) and 95% confidence intervals (ci) were reported. variables with a p-value < 0.05 in the univariate analyses and variables of clinical significance were selected for inclusion. 3. results 3.1. baseline characteristics of participants eight hundred and eighty-nine individuals aged 65 years and above were intubated at the studied ed from 2015 to 2019 (7.5% ≥ 85 years and 61.5% male). baseline characteristics of studied cases are summarized in table 1. 8% were nursing home residents. 424 (52 %) patients had a cci of ≥ 5, while 660 (74%) patients had an isar score of ≥ 2, and 203 (23%) cases had an apache-ii score of ≥ 35. a total of 316 (36%) patients had a pre-intubation gcs of 3. of the 889 included individuals, 220 (25%) underwent crash intubation for cardiac arrest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e16 table 1: baseline characteristics of intubated elder adults in emergency department (ed) variable value (%) age (years) 65 – 74 505 (56.8) 75 – 84 317 (35.7) ≥ 85 67 (7.5) gender male 547 (61.5) female 342 (38.5) origin before ed visit nursing home 68 (7.6) others 821 (92.4) charlson comorbidity index (cci) < 5 465 (52.3) ≥ 5 424 (47.7) identification of seniors at risk (isar) < 2 229 (25.8) ≥ 2 660 (74.2) apache-ii score 10 – 24 336 (37.8) 25 – 34 350 (39.4) ≥ 35 203 (22.8) pre-intubation glasgow coma scale (gcs) 15 204 (22.9) 4 – 14 369 (41.5) 3 316 (35.5) indication of intubation cardiac arrest 220 (24.7) other 669 (75.3) admission diagnosis cardiac arrest 220 (24.7) sepsis/septic shock 142 (16.0) acs/heart failure 79 (8.9) pneumonia 89 (10.0) cerebrovascular accident 88 (9.9) traumatic brain injury 51 (5.7) others 220 (24.7) apache-ii: acute physiology and chronic health evaluation -ii; acs: acute coronary syndrome. 3.2. univariate analysis of all intubated older adults, 635 (71.4%) died in the hospital. table 2 summarizes the univariate analysis of factors associated with in-hospital mortality. there were a significant association between age (p < 0.001), nursing home residency (p = 0.008), cci≥ 5 (p = 0.001), apache-ii score (p < 0.001), pre-intubation gcs (p < 0.001), cardiac arrest as indication of intubation (p < 0.001), diagnosis on admission (p < 0.001), length of stay (p < 0.001), and length of ventilation (p = 0.003) and in-hospital mortality of intubated older adults in emergency department. 3.3. predictors of in-hospital mortality age ≥ 85 years (hr= 1.270; 95%ci=1.074 to 1.502) and 75 to 84 years (hr=1.642; 95%ci=1.167 to 2.076), cardiac arrest as indication of intubation (hr: 1.882; 95% ci: 1.554 – 2.279), and apache-ii scores 25 – 34 (hr: 1.423; 95% ci: 1.171 1.730) and ≥ 35 (hr: 1.789; 95%ci: 1.418 2.256) were amongst the independent predictive factors of in-hospital mortality among intubated older adults in emergency department. 4. discussion the management of the critically ill older adults, especially in the intensive care unit is resource heavy with a corresponding increase in healthcare cost burden (22, 23). hence, early decision making on the risk-benefit of intubation and ventilation of critically ill older persons in the emergency department is paramount. in this study, nearly three out of four individuals aged 65 years and over intubated in the ed died in hospital. if only those aged 85 years and above were considered, the inpatient mortality rate was 90%. this proportion was far higher than that reported by a similar study conducted in a developed country, which reported a mortality rate of 33% (5). while this discrepancy could be accounted for by better prehospital and critical care (24), an alternative explanation could also be the far higher caseloads handled in the ed in developing countries with patients presenting at a later stage of illness (25). this is also supported in a study in china and iran during the covid-19 pandemic, in which critically ill older persons had a significantly higher mortality rate than those younger(26, 27). another possible explanation was the lack of validated criteria or risk scoring on the selection of patients who might benefit from critical care as supported by a study in india (28). however, our study supported the poorer outcome of older persons aged more than 85 years old as reported by bertrain guidet et al. (29). providing care for older patients does not mean subjecting them to aggressive treatments, such as intubation, which may lead to avoidable suffering to the patients and their families, and unnecessarily burdening the healthcare system (30). previously published data have reported high mortality following adult out-of-hospital or in-hospital cardiac arrest (18, 31), but little is known about the effect of most interventions during cardiac arrest, including drugs and the use of advanced airway management. in a study involving adult patients with in-hospital cardiac arrest, the initiation of tracheal intubation within the first 15 minutes of resuscitation, compared with no intubation, was associated with decreased survival to hospital discharge (18). within this study, older adults who underwent emergency crash intubation during a cardiac arrest event had a higher inpatient mortality, highlighting the potential futility of intubation in the majority of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. idzwan zakaria et al. 4 table 2: comparing the characteristics of patients between survived and non-survived cases who were intubated in emergency department predictors in-hospital mortality p-value yes (n = 635) no (n = 254) age (year) 65 – 74 328 (65.0) 117 (35.0) < 0.001 75 – 84 247 (77.9) 70 (22.1) ≥ 85 60 (89.6) 7 (10.4) gender male 379 (69.3) 168 (30.7) 0.074 nursing home yes 58 (85.3) 10 (14.7) 0.008 cci ≥ 5 yes 326 (76.9) 98 (23.1) 0.001 isar ≥ 2 yes 477 (72.3) 183 (27.7) 0.344 apache-ii 10 – 24 193 (57.4) 143 (42.6) 25 – 34 260 (74.3) 90 (25.7) < 0.001 ≥ 35 182 (89.7) 21 (10.3) pre-intubation gcs 15 121 (59.3) 83 (40.7) 4 – 14 249 (67.5) 120 (32.5) < 0.001 3 265 (83.9) 51 (16.1) indication of intubation cardiac arrest 200 (90.9) 20 (9.1) < 0.001 admission diagnosis cardiac arrest 200 (90.9) 20 (9.1) sepsis, septic shock 116 (81.7) 26 (18.3) acs/heart failure 55 (69.6) 24 (30.4) < 0.001 pneumonia 60 (67.4) 29 (32.6) stroke/ich 67 (76.1) 21 (23.9) traumatic brain injury 37 (72.5) 14 (27.5) others 100 (45.5) 120 (54.5) duration of ventilation (week) < 1 438 (75.1) 145 (24.9) 1-2 159 (63.6) 91 (36.4) 0.003 >4 38 (67.9) 18 (32.1) length of hospital stay (week) < 1 435 (96.5) 16 (3.5) 1-4 154 (48.7) 162 (51.3) < 0.001 > 4 46 (37.7) 76 (62.3) data are presented as number (%). cci: charlson comorbidity index; isar: identification of seniors at risk; apache-ii: acute physiology and chronic health evaluation-ii; gcs: glasgow coma scale; acs: acute coronary syndrome; ich: intracranial hemorrhage. older adults who suffer cardiac arrest in the hospital. however, this does not necessarily advocate blanket avoidance of artificial ventilation in all older adults with cardiac arrest in hospital, and further research is required to ensure that the minority who will survive to discharge are not deprived of life saving treatment and are accurately identified. the apache-ii score has long been established as an accurate measure of mortality among critically ill individuals (13, 14, 32). however, it has yet to be evaluated as a measure for survival following intubation in older patients. within this study, the apache-ii emerged as an independent predictor of in-hospital mortality. although presence of comorbidities was associated with inpatient mortality within the univariate analysis, it did not emerge within the final predictor model. multiple studies have identified poorer outcomes in critically ill older adults with more underlying comorbidities (12, 20, 33). this has led to the common practice among health care workers, using comorbidities to facilitate end-oflife decisions for critically ill older adults. our findings imply that the influence of comorbidity on inpatient mortality this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e16 table 3: independent predictors of in-hospital mortality among intubated older adults in emergency department based on cox’s regression survival analysis predictors b hazard ratio (95% ci) age ( years) 65 – 74 (reference) 75 – 84 0.239 1.270 (1.074 1.502) ≥ 85 0.496 1.642 (1.167 2.076) indication of intubation cardiac arrest 0.632 1.882 (1.554 – 2.279) apache-ii score 10 – 24 25 – 34 0.353 1.423 (1.171 1.730) ≥ 35 0.582 1.789 (1.418 2.256) ci: confidence interval; apache-ii: acute physiology and chronic health evaluation-ii. is accounted for by severity of illness, and the latter should be considered as the determinant of likelihood of survival to discharge rather than the former in the context of older adults who are intubated. numerous frailty assessment tools have been developed based on adverse outcomes, which included mortality and hospitalization. a previous study found that critically ill frail patients have higher in-hospital mortality than non-frail patients, and the frail survivors were also more likely to become functionally dependent (34). the identification of senior at risk (isar) tool has been developed as an identifier of those at high risk of adverse health outcomes after an emergency department visit. however, within this study, when applied within the context of intubation, frailty identified with the isar did not predict survival to discharge. our finding, therefore, suggests that once an older individual is intubated, the likelihood of survival is determined by severity of illness rather than frailty status before admission, but age alone still plays a significant role in influencing outcomes of artificial ventilation. this does imply that frailty measured using the isar tool does not predict intubation outcomes and is not an appropriate tool to aid decisions against intubation in older adults (35). this does not conform with other studies advocating the use of frailty scores as a modality of estimating outcome (29). a possible explanation is that isar has a poor to fair predictive validity in prediction of outcome and should not be use alone for identifying older persons at risk of adverse outcome in the emergency department (36). decisions to withhold life-sustaining treatment such as endotracheal intubation are often challenging for medical professionals, with various cultural and religious views potentially influencing such decisions (37). appropriate training for healthcare professionals on medical ethics and communication skills may help reduce the burden of delivery of lifeprolonging treatment that is likely to be futile, and this could be additionally facilitated with guidelines and decision aids. 5. limitation this study is limited by its retrospective design, with potential inaccuracies associated with retrospective data collection such as misinterpretation of records in the emr. it was not possible to verify the accuracy of the predictor scores recorded within the emr. nevertheless, the issue of high inpatient mortality rates in those intubated in the ed within our setting has been clearly highlighted, with important ethical and resource implications. future studies should investigate the reasons underlying this high mortality rate, as well as develop accurate predictor tools to aid decision making. in addition, evaluation of the role of ethics and communication training, guidelines, and decision aids should also be considered in this regard. 6. conclusion age ≥ 75, cardiac arrest as indication for intubation, and apache-ii scores ≥ 25 were independent predictive factors of in-hospital mortality following intubation of older adults in the ed. frailty and comorbidities evaluated with the isar tool and cci, respectively, were not predictors of inhospital mortality, challenging the existing practice of using pre-hospitalization frailty status and comorbidity burden to guide decision for or against intubation. 7. declarations 7.1. acknowledgments the authors are grateful to the medical records department and the staff at the department of emergency medicine, ummc for facilitating data collection. 7.2. authors’ contributions mohd idzwan and tan maw pin designed the protocol on methodology, ethical approval, writing, review and editing the manuscript. mohd idzwan also supervised the complethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. idzwan zakaria et al. 6 tion of the manuscript. nor hadila was involved in research literature review, gaining ethical approval, sample collection, data analysis, writing and editing the manuscript. all authors reviewed and edited the manuscript and approved the final version of the manuscript. 7.3. funding and supports this was an unfunded study. 7.4. conflict of interest none declared. 7.5. availability of data the datasets generated and analyzed during the current study are available from mohd idzwan bin zakaria. references 1. shetty p. grey matter: ageing in developing countries. lancet. 2012;379(9823):1285-7. 2. current population estimates, malaysia, 2020 [press release]. department of statistics malaysia, 15th july 2020. https://www.dosm.gov.my/v1/index.php?r=column/pdf prev&id=ovbywjg5ykq3mwfzrtn5bdjiaevhzz09#:te xt=malaysia’s%20population%20in%202020%20is,to%20 3.0%20million%20(2020). 3. mafauzy m. the problems and challenges of the aging population of malaysia. malays j med sci. 2000;7(1):1-3. 4. welie jv, ten have ha. the ethics of forgoing lifesustaining treatment: theoretical considerations and clinical decision making. multidiscip. respir. med. 2014;9(1):1-8. 5. ouchi k, jambaulikar gd, hohmann s, george nr, aaronson el, sudore r, et al. prognosis after emergency department intubation to inform shared decisionmaking. j am geriatr soc j. 2018;66(7):1377-81. 6. foerch c, kessler k, steckel d, steinmetz h, sitzer m. survival and quality of life outcome after mechanical ventilation in elderly stroke patients. j. neurol. neurosurg. psychiatry. 2004;75(7):988-93. 7. steinhauser ke, christakis na, clipp ec, mcneilly m, mcintyre l, tulsky ja. factors considered important at the end of life by patients, family, physicians, and other care providers. jama. 2000;284(19):2476-82. 8. lagu t, zilberberg md, tjia j, pekow ps, lindenauer pk. use of mechanical ventilation by patients with and without dementia, 2001 through 2011. jama intern med. 2014;174(6):999-1001. 9. feng y, amoateng-adjepong y, kaufman d, gheorghe c, manthous ca. age, duration of mechanical ventilation, and outcomes of patients who are critically ill. chest. 2009;136(3):759-64. 10. wang r, mouliswar m, denman s, kleban m. mortality of the institutionalized old-old hospitalized with congestive heart failure. arch. intern. med. 1998;158(22):2464-8. 11. salvi f, morichi v, grilli a, lancioni l, spazzafumo l, polonara s, et al. screening for frailty in elderly emergency department patients by using the identification of seniors at risk (isar). j. nutr. health aging. 2012;16(4):313-8. 12. song se, lee sh, jo e-j, eom js, mok jh, kim m-h, et al. the prognostic value of the charlson’s comorbidity index in patients with prolonged acute mechanical ventilation: a single center experience. tuberc respir dis. 2016;79(4):289-94. 13. qiao q, lu g, li m, shen y, xu d. prediction of outcome in critically ill elderly patients using apache ii and sofa scores. j. int. med. res. 2012;40(3):1114-21. 14. kleinpell rm, ferrans ce. factors influencing intensive care unit survival for critically ill elderly patients. heart & lung. 1998;27(5):337-43. 15. broos p, d’hoore a, vanderschot p, rommens p, stappaerts k. multiple trauma in elderly patients. factors influencing outcome: importance of aggressive 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1987;40(5):373-83. 21. knaus wa, draper ea, wagner dp, zimmerman je. apache ii: a severity of disease classification system. crit care med. 1985;13(10):818-29. 22. chin-yee n, d’egidio g, thavorn k, heyland d, kyeremanteng k. cost analysis of the very elderly admitted to intensive care units. crit care. 2017;21(1):1-7. 23. angus dc. admitting elderly patients to the intensive care unit—is it the right decision? jama. 2017;318(15):1443-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e16 24. de carvalho ia, epping-jordan j, pot am, kelley e, toro n, thiyagarajan ja, et al. organizing integrated health-care services to meet older people’s needs. bull world health organ. 2017;95(11):756. 25. mohd mokhtar ma, pin tm, zakaria mi, hairi nn, kamaruzzaman sb, vyrn ca, et al. utilization of the emergency department by older residents in kuala lumpur, malaysia. geriatr gerontol int. 2015;15(8):944-50. 26. yang x, yu y, xu j, shu h, liu h, wu y, et al. clinical course and outcomes of critically ill patients with sarscov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study. lancet respir med. 2020;8(5):475-81. 27. sanie jahromi ms, aghaei k, taheri l, kalani n, hatami n, rahmanian z. [intensive care unit of covid-19 during the different waves of outbreaks in jahrom, south of iran]. j med chem sci. 2022; 5(5): 734-742. persian 28. chopra s, pednekar s, karnik nd, londhe c, pandey d. a study of the outcome of critically ill elderly patients in a tertiary care hospital using sofa score. indian j crit care med. 2021;25(6):655. 29. guidet b, vallet h, boddaert j, de lange dw, morandi a, leblanc g, et al. caring for the critically ill patients over 80: a narrative review. ann intensive care. 2018;8(1):1-15. 30. cardona m, turner rm, chapman a, alkhouri h, lewis et, jan s, et al. who benefits from aggressive rapid response system treatments near the end of life? a retrospective cohort study. jt comm j qual patient saf. 2018;44(9):505-13. 31. hirlekar g, karlsson t, aune s, ravn-fischer a, albertsson p, herlitz j, et al. survival and neurological outcome in the elderly after in-hospital cardiac arrest. resuscitation. 2017;118:101-6. 32. wu aw, rubin hr, rosen mj. are elderly people less responsive to intensive care? j am geriatr soc. 1990;38(6):621-7. 33. ferrante le, pisani ma, murphy te, gahbauer ea, leosummers ls, gill tm. functional trajectories among older persons before and after critical illness. jama intern med. 2015;175(4):523-9. 34. bagshaw sm, stelfox ht, mcdermid rc, rolfson db, tsuyuki rt, baig n, et al. association between frailty and short-and long-term outcomes among critically ill patients: a multicentre prospective cohort study. cmaj. 2014;186(2):e95-e102. 35. wilkinson dj. frailty triage: is rationing intensive medical treatment on the grounds of frailty ethical? am j bioeth. 2021;21(11):48-63. 36. yao j-l, fang j, lou q-q, anderson rm. a systematic review of the identification of seniors at risk (isar) tool for the prediction of adverse outcome in elderly patients seen in the emergency department. int j clin exp med. 2015;8(4):4778. 37. el jawiche r, hallit s, tarabey l, abou-mrad f. withholding and withdrawal of life-sustaining treatments in intensive care units in lebanon: a cross-sectional survey of intensivists and interviews of professional societies, legal and religious leaders. bmc med ethics. 2020;21(1):1-11. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 20 emergency (2013); 1 (1): 20-23 original research emergency department performance indexes before and after establishment of emergency medicine behrooz hashemi, alireza baratloo*, farhad rahmati, mohammad mehdi forouzanfar, maryam motamedi, saeed safari department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: emergency department performance index (epi) greatly influences the function of other hospital’s units and patient satisfaction. recently, the iranian ministry of health has defined specific national epi containing five indexes. in the present study the performance indexes of emergency department (ed) in one educational hospital has been assessed before and after establishment of emergency medicine. methods: in the present crosssectional study the ed of shohadaye tajrish hospital, tehran, iran was assessed during one-year period from march 2012 to february 2013. the study was divided into two six-month periods of before and after establishment of emergency medicine. five performance indexes including: the percentage of patients were disposed during 6-hour, leaved the ed in a 12-hour, had unsuccessful cardiopulmonary resuscitations (cpr), discharged against medical advice, and the mean time of triage were calculated using data of department of medical records on daily patients’ files. then, mann-whitney u test was used to make comparisons at p<0.05. results: the average triage time decreased from 6.04 minutes in the first six months to 1.5 minutes in the second six months (p=0.06). the percentage of patients leaving the ed in a 12-hour decreased from 97.3% to 90.4% (p=0.004). however, the percentage of disposed patients during 6-hour (p=0.2), unsuccessful cpr (p=0.34) and discharged against medical advice (p=0.42) did not differ between the two periods. conclusion: it seems that establishment of emergency medicine could be able to improve ed performances indexes such as time to triage and leave in a 12-hour period. key words: emergency department performance index; emergency medicine; patient discharge; triage cite this article as: hashemi b, baratloo a, rahmati f, forouzanfar mm, motamedi m, safari s. emergency department performance indexes before and after establishment of emergency medicine. emergency. 2013; 1(1):20-3. introduction:1 mergency department performance index (epi) greatly influences the function of other hospital’s units and also patient satisfaction. base on official reports iran’s emergency departments (ed) admit approximately 30 million critically ill and ambulatory patients all over the country. this great population increases the potential of medical errors and the duration of patients’ waiting time in ed (1-3). there are various methods to assess the performance and function in different organizations. these methods generally originate from theories, attitudes or situations. they can evaluate the achievement of predetermined goals or aims in an organization. continuous and correct implementation of these methods improves the function and efficacy of units (4-6). epi as one of these methods can be used to monitor the performance of eds (4). recently, the ira *corresponding author: alireza baratloo; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. mobile phone: +989122884364, fax: +982122721155 email: alirezabaratloo@yahoo.com received: 7 september 2013; accepted: 25 november 2013 nian ministry of health has defined specific national epi containing five indexes for the assessment of eds’ performance. this is measurable and realistic assessment method with definite frameworks and time intervals (7, 8). these five indexes consist of 1: the percentages of patients were disposed during 6-hour of presentation to ed; 2: the percentage of patients leaved the ed in a 12-hour period; 3: percentage of unsuccessful cardiopulmonary resuscitations (cpr); 4: percentage of discharge against medical advice; and 5: the average time of triage (panel 1). based on the above mentioned, in the present study the performance indexes of ed in one educational hospital has been assessed before and after establishment of emergency medicine. methods: study design and setting in the present cross-sectional study the ed of shohadaye tajrish hospital (shahid beheshti university of medical sciences, tehran, iran) was assessed during one-year period from march 2012 to february 2013. this assessment was carried out based on iranian national epi designed by ministry of health (panel 1). the e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 21 emergency (2013); 1 (1): 20-23 study was divided into two six-month periods of before and after establishment of emergency medicine. data collection all necessary data, assigned in panel one, were collected using patients’ files at the end of each 24-hour shift by department of medical records’ staffs. then the data were rechecked by the emergency unit manager and were entered into the database designed for the study. finally, the five indexes calculated for each day, separately. statistical analysis data were entered into spss 21.0 statistical software and reported in means ± standard deviations. differences between the two periods of the study were evaluated by mann-whitney u test. also, since changes made after the establishment of emergency medicine, probably takes time to appear, the difference between the first and last quarters of study period were compared. statistical significance was defined at p<0.05. results: the mean of triage time was 6.04 minutes at the first six-month, decreasing to 1.5 minutes during the second half of the study period (p=0.016). the percentage of patients leaving the emergency unit in a 12-hour at the first and second study periods were 97.3% and 90.4%, respectively (p=0.004). there were no significant changes in the percentage of cases disposed in a 6-hour (p=0.2), the percentage of unsuccessful cprs (p=0.34), and percentage of discharge against medical advice (p=0.42) (table 1). evaluation of differences in performance indexes between the first and last quarters of the study period showed no significant differences between any of the indexes (table 2). comparing the first and last quarter showed 1.1% decrease in the percentage of patients had been disposed during the first 6-hour, 7.6% in patients leaving the emergency unit in a 12-hour, and 60% in the mean of triage time (p>0.05). the percentage of unsuccessful cprs and the percentage of discharge against medical advice were not significantly different between two quarters. discussion: the finding of the present study showed that establishment of emergency medicine results in a more efficacious triage. on the other hand, the percentage of patients leaving the emergency unit in the 12-hour period decreased significantly. although the number of patients discharge against medical advice and the mean of cases disposed in a 6-hour decreased at the end of the study, the differences were not statistically significant. the decrease in triage time can be explained by the fact that in the hospital under study, before establishment of emergency medicine, triage was carried out by general practitioners. this kind of triage had two main disadvantages: first, the triage duration was long and second; all the triage levels (from level 1 to level 5, based on emergency severity index) were referred to the emergency ward. however, after establishment of emergency medicine, triage of patients was carried out by the panel 1: national emergency department performance index (epi) index data necessary of calculation the method used for calculation the percentages of patients were disposed during 6-hour the number of patients were disposed in 6 hours; the total number of patients hospitalized temporarily; the time of admission into the emergency ward; the time of disposition the ratio of patients hospitalized temporarily in the emergency ward, whose cases were disposed in 6 hours to the total number of patients hospitalized temporarily in the emergency ward the percentage of patients leaving the ed1 in a 12hour the number of patients hospitalized temporarily in the emergency ward; the times of admission into and discharge from the emergency ward the ratio of patients hospitalized temporarily in the emergency ward, whose cases were disposed in 12 hours from the admission and discharged to the total number of patients hospitalized temporarily in the emergency ward unsuccessful cprs2 the total number of cprs; the number unsuccessful cprs the ratio of the number of unsuccessful cprs to the total number of cprs at a time interval; successful cpr was defined as cases in which the patient had spontaneous circulation and did not need cpr again for at least 20 minutes discharge against medical advice the number of patients hospitalized temporarily; the number of patients discharge against medical advice the ratio of patients discharge against medical advice despite the advice of the emergency physician to the total number of patients hospitalized temporarily in the emergency ward mean time of triage duration of triage; triage level; the total number of the patients in the same triage level the ratio of the total duration of patient triage to the total number of patients in the same triage level 1: emergency department; 2: cardiopulmonary resuscitations this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 22 hashemi et al emergency residents, which resulted in a shorter triage time and referral of level 5 patients to the outpatient clinic. this fact resulted in a change in the pattern of patients referring to the emergency ward, i.e. the number of critically ill patients increased. since, there were lacking resource regarding number of intensive care unit (icu) and monitoring room these patients remained in the emergency ward. therefore, during the second half of the study period the percentage of patients who remained in the emergency unit for more than 12-hour, subsequently increased. the previous studies have shown that one of the factors responsible for crowdedness of emergency units is patients’ not leaving the emergency ward due to any causes (9-11). queuing theory, suggests that an increase in using a service results in an increase in waiting to receive services (12, 13). theoretically, when the capacity of a system remains low, the waiting duration of users for the service will increase (12). extension of this theory to the emergency unit emphasizes the fact that an increase in the occupation of hospital beds results in an increase in crowdedness of emergency units, subsequently. bowker and stewart reported a frequency of 98% for unsuccessful cpr cases (14). peberdy et al reported a frequency rate of 87% for such cases (15). as shown in tables 1 and 2, there was an increase in the number of unsuccessful cprs in the present study. although the difference was not statistically significant, it was noticeable (55.7% vs. 88%). such a difference was attributed to improving and correcting the method used to record unsuccessful cprs. by definition, a cpr is successful if the patient has spontaneous circulation after the procedure and does not require repetition of cpr for at least 20 minutes. however, before establishment of emergency medicine, each cpr, which resulted in spontaneous circulation in the patient, was considered a successful cpr (even if cpr was again needed in less than 20 minutes). therefore, correction of the method used to register the reports resulted in more accurate and reliable statistics. the literature review in the present study did not bring up a study, which has particularly evaluated the performance indexes of emergency units. the majority of studies available have evaluated the management and human resource aspects. for example, rahman et al reported that hospitals in which the head of the emergency unit is an emergency medicine specialist with experienced personal exhibit better performance in rendering emergency services (16). movahedina et al evaluated timing indexes in an emergency unit and reported that timing indexes in the emergency unit of firouzgar hospital were standard, which was attributed to the presence of emergency physicians’ establishment in the unit (17). other studies are in opposing opinion (18, 19). limitation the patients referred to ed during two period of study are not necessarily the same. on the other hand, differences may be due to more accurate fulfilling patient’s timetables after nursing educational courses. in addition, our hospital guidelines and resistance of other wards against admission of patients, limit on-time disposition. conclusion: it seems that establishment of emergency medicine could be able to improved emergency department performances indexes such as time to triage and 12-hour table 1: comparison of performance indexes between the first and second halves of the study index first 6 months second 6 months p mean sd1 mean sd mean of triage time (minutes) 6.04 7.7 1.5 0.27 0.016 patients were disposed in 6 hours (%) 94.4 1.6 93.1 1.8 0.2 patients were disposed during 6 hours, discharged during 12-hour (%) 97.3 0.8 90.4 0.6 0.004 unsuccessful cprs (%) 64.9 21.1 74.4 13.2 0.34 discharge against medical advice (%) 20.7 1.1 19.4 2.0 0.42 1: standard deviation table 2: comparison of performance indexes between the first and last quarters of the study index first quarter last quarter p mean sd1 mean sd mean of triage time (minutes) 3.5 0.25 1.4 0.14 0.08 the patients whose cases were disposed in 6 hours (%) 95.0 0.94 93.9 0.17 0.08 the patients discharged from the emergency ward in 12 hours (%) 97.5 0.8 89.9 0.47 0.08 unsuccessful cprs (%) 55.7 20.1 88.0 14.2 0.13 discharge against medical advice (%) 20.2 1.4 20.8 1.6 0.56 1: standard deviation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 23 emergency (2013); 1 (1): 20-23 disposition. acknowledgements: the authors would like to thank all the emergency unit personnel and the staff of the medical statistics center of shohadaye tajrish hospital. special thanks are also due to ms. maryam nikookalam for her sincere assistance in carrying out this research study. conflict of interest: the authors declare that there are no conflicts of interest. funding: this study was performed based on a dissertation submitted to shahid beheshti university of medical sciences in partial fulfillment of the requirements for an undergraduate degree in medicine. no other supports, including financial support, were involved. authors’ contribution: all authors contribute in drafting/revising the manuscript, study concept or design, analysis or interpretation of data. references: 1. geelhoed gc, de klerk nh. emergency department overcrowding, mortality and the 4-hour rule in western australia. med j aust. 2012;196(2):122-6. 2. richardson db. increase in patient mortality at 10 days associated with emergency department overcrowding. med j aust. 2006;184(5):213. 3. trzeciak s, rivers e. emergency department overcrowding in the united states: an emerging threat to patient safety and public health. emerg med j. 2003;20(5):402-5. 4. casalino e, choquet c, julien b, et al. predictive variables of an emergency department quality and performance indicator: a 1-year prospective, observational, cohort study evaluating hospital and emergency census variables and emergency department time interval measurements. emerg med j. 2012. 5. goroll ah, mulley ag. primary care medicine: office evaluation and management of the adult patient: wolters kluwer health; 2012. 6. nordstrom k, zun ls, wilson mp, et al. medical evaluation and triage of the agitated patient: consensus statement of the american association for emergency psychiatry project beta medical evaluation workgroup. west j emerg med. 2012;13(1):3. 7. dixon a, ham c. setting objectives for the nhs commissio ning board. brit med j. 2012;345. 8. guidotti tl. what key performance indicators can be used in occupational health? j occup environ med. 2012;54 (8):1042-3. 9. bagust a, place m, posnett jw. dynamics of bed use in accommodating emergency admissions: stochastic simulation model. brit med j. 1999;319(7203):155. 10. forster aj, stiell i, wells g, lee aj, van walraven c. the effect of hospital occupancy on emergency department length of stay and patient disposition. acad emerg med. 2003;10 (2):127-33. 11. han jh, zhou c, france dj, et al. the effect of emergency department expansion on emergency department overcro wding. acad emerg med. 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[persian]. 17. movahednia s, partovishayan z, bastanitehrani m. a survey of timing indicators of emergency department at firoozgar hospital: 2012. j health administ. 2013;16(51):95102. 18. tabibi sj, najafi b, shoaie s. waiting time in the emergency department in selected hospitals of iran university of medical sciences in 2007. pejouhesh. 2009;33(2):117-22. [persian]. 19. zohoor a, pilevar zadeh m. study of speed of offering services in emergency department at kerman bahonar hospital in 2000. razi j med sci. 2003;10(35):413-9. [persian]. emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 15 emergency (2013); 1 (1): 15-19 original research sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure afshin amini1, razieh eghtesadi1*, ali mohammad feizi2, behnam mansouri3, hamid kariman1, ali arhami dolatabadi1, hamidreza hatamabadi1, ali kabir1 1. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of radiology, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of neurology, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: timely diagnosis and treatment of post-traumatic elevated intracranial pressure (eicp) could be reduced morbidity and mortality, and improved patients’ outcome. this study is trying to evaluate the diagnostic accuracy of sonographic optic nerve sheath diameter (onsd) in detection of eicp. methods: sonographic onsd of patients with head trauma or cerebrovascular accident suspicious for eicp were evaluated by a trained chief resident of emergency medicine, who was blind to the clinical and brain computed tomography scan (bct) findings of patients. immediately after ultrasonography, bct was performed and reported by an expert radiologist without awareness from other results of the patients. finally, ultrasonographic and bct findings regarding eicp were compared. to evaluate the ability of sonographic onsd in predicting the bct findings and obtain best cutoff level, receiver operating characteristic (roc) curve were used. sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), positive likelihood ratio (plr), and negative likelihood ratio (nlr) of sonographic onsd in determining of eicp was calculated. p < 0.05 was considered as statistically significant. results: there were 222 patients (65.3% male), with mean age of 42.2±19.5 years (range: 16-90 years). bct showed signs of eicp, in 28 cases (12.6%). the means of the onsd in the patients with eicp and normal icp were 5.5 ± 0.56 and 3.93 ± 0.53 mm, respectively (p<0.0001). roc curve demonstrated that the best cut off was 4.85 mm. sensitivity, specificity, ppv, npv, plr, and nlr of onsd for prediction of eicp were 96.4%, 95.3%, 72.2%, 98.9%, 20.6, and 0.04, respectively. conclusion: sonographic diameter of optic nerve sheath could be considered as an available, accurate, and noninvasive screening tool in determining the elevated intracranial pressure in ca ses with head trauma or cerebrovascular accident. key words: intracranial pressure; traumatic brain injury; ultrasonography; optic nerve; tomography cite this article as: amini a, eghtesadi r, feizi am, mansouri b, kariman h, arhami dolatabadi a, hatamabadi h, kabir a. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. emergency. 2013; 1(1):15-9. introduction:1 ead injury is the most common cause of roadtraffic-related morbidity and mortality of all ages (1). traumatic brain injuries and related increasing intracranial pressure (eicp) might result in the worsening of patient outcomes (2). timely diagnosis and treatment of post-traumatic eicp could be reduced morbidity and mortality of patients. there are some invasive, expensive or expert needed methods as lumbar puncture, magnetic resonance imaging (mri), and computed tomography scan (ct-scan) for detection of eicp (3). physical examination is not always reliable and also, some signs of eicp such as pupil edema are late coming or hardly detected (4). so, reliable, accessi *corresponding author: razieh eghtesadi; department of emergency medicine, imam hossein hospital, shahid madani avenue, tehran, iran. tel: +989136470851; fax:+983117923445; email: razieeqtesadi@yahoo.com received: 1 october 2013; accepted: 19 november 2013 ble, easy to learn and noninvasive technique for this purpose, like sonography, is of interest for clinician. some studies have assessed the diagnostic accuracy of sonography in animal models, children, and adults in emergent or even in healthy subjects (5-9). these studies were heterogenous from different target population in different settings and their results are not completely applicable for other persons. our previous study, showed that the sonographic onsd might be considered as a strong and accurate predicting factor for detection of eicp (10). in this study, we prospectively evaluated the diagnostic accuracy of sonography for detecting eicp in a setting of emergency patients with head trauma or suspicious cerebrovascular accident in a relatively larger sample than previous similar studies. moreover, we intended to determine the best cut off values of onsd for detecting eicp in comparison with brain computed tomography scan (bct) findings. h this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 16 amini et al methods: study design and setting in this diagnostic trial, we recruited 222 patients suspicious for eicp due to head trauma or cerebrovascular accident referring to emergency department of imam hossien hospital, tehran, iran between may and october 2011. the protocol of this study was reviewed and approved by shahid beheshti university of medical sciences ethics committee (code: 6476). the study protocol conformed to the ethical guidelines of the declaration of helsinki. after complete explanation about the procedure for the patient, written informed consent was received. surrogate consent by guardian was obtained in case patients with altered mental status. participants the subjects with head trauma or cerebrovascular accident were enrolled. cases with age < 16, direct trauma to the eye, ophthalmic diseases, and under treatment with medications affecting on intracranial pressure were excluded. sample size was determined according to sample size calculation for formula of diagnostic tests, considering sensitivity=0.8, specificity=0.8, and α=0.05. therefore, sample size was estimated to be 222 cases. intervention before doing brain ct-scan for definite diagnosis, onsd of both eyes was determined by ultrasonography. we did ultrasonography before awareness from the result of bct to prevent diagnostic suspicious bias. sonographer was also blind to the patient’s clinical condition. ultrasongraphies of the optic nerve was performed by chief resident of emergency medicine who was trained for measurement of onsd by a radiologist. transorbital ultrasonography of the optic nerve was performed using a 7.5 mhz linear transducer (hs2000, honda, korea) sized 5.5×1 cm. the patient was relaxed, calm, in supine position with closed eyes. it was done from the most upper part of the upper eyelid, 3 mm before entrance of the optic nerve to the globe. the onsd was calculated as the horizontal distance between the 2 cursors (figure 1). one time measurement was taken for each optic nerve. the mean onsd registered was the average value obtained from measurements of both right and left eyes, despite the fact that previous studies have shown the presence of intraocular symmetry between the ond/onsds of fellow eyes (11, 12). immediately after ultrasonography, bct was performed and reported by one expert radiologist without awareness from the results of the sonography. signs of eicp in bct were effacement of sulci, significant edema, midline shifting, and collapse of ventricle(s). finally, results of ultrasonography were compared with bct findings. age, gender, level of consciousness according to glasgow coma scale (gcs), type of injury (trauma or cerebrovascular accident), onsd of both eyes by ultrasonography and bct findings were determined in all patients. statistical analysis we used mean and standard deviation, for description of quantitative variables. the relation of gcs and onsd was assessed using person correlation coefficient. to evaluate the ability of onsd in predicting the bct results and obtain best cut-off level, receiver operating characteristic (roc) curve and its area under the curve (auc) were used. in addition, in specific cut-point we determined operating characteristics consist of sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), positive likelihood ratio (plr), and negative likelihood ratio (nlr). differences or correlations with p < 0.05 were considered statistically significant. we used stata version 11.0 statistical software in analysis. results: there were 222 patients (65.3% male), with mean age of 42.2±19.5 years (range: 16-90 years). a summary of patients’ demographic data is presented in table 1. type of injury was trauma in 204 cases (91.9%) and cerebrovascular accident in 18 (8.1%). only 27 (12.2%) cases had gcs<15. bct finding was confirmed 28 (12.6%) cases of eicp. among cases with decreased gcs, 13 (48.1%) patients had positive bct findings. the means of sonographic onsd on the left and right sides were 4.2±0.8 and 4.1±0.8 mm, respectively (p = 0.41). the mean of the sonographic diameters of the optic nerve sheath of the two eyes was 4.1 ± 0.8 mm, with no significant relationships with patient age (p=0.99) and gender (p=0.19). the means of the onsd in the patients with eicp and normal icp were 5.5 ± 0.56 and 3.93 ± 0.53 mm, respectively (p<0.0001). gcs was inversely associated with right (r=-0.37, p<0.001), left (r=-0.26, p<0.001) and mean onsd (r=-0.33, p<0.001). roc analysis demonstrated that the best cut off was 4.85 mm (figure 2). area under the curve for diagnosis of the eicp was 0.95 (95% ci: 0.89-1.0). sensitivity and specificity of onsd for prediction of eicp were 96.4 % (95% ci: 83.9-99.8) and 95.3% (95% ci: 90.4-99.9), respectively. in addition positive and negative predictive value were 72.2% (95% ci: 67.4-79.2) and 98.9% (95% ci: 95.8-99.8), respectively. positive and negative like figure 1: sonographic optic nerve sheath diameter (onsd). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 17 emergency (2013); 1 (1): 15-19 lihood ratio of onsd for detection of eicp was 20.6 (95% ci: 18.2-22.4) and 0.04 (95% ci: 0.02-0.06), respectively. discussion: based on the main result of this study onsd had acceptable sensitivity, specificity, npv, and ppv for detection of eicp at cut-off value of 4.85 mm. the probability to have eicp if onsd is less than 4.85 mm is 0.04, which is sufficiently very low. previous studies have considered a cut off range of onsd in predicting of eicp between 5 and 5.9 mm (table 2). low ppv in this study, despite high sensitivity and specificity, could be due to low number of cases with positive bct findings. during last decades, many studies have shown that the onsd can noninvasively predict the eicp (13-15). one study has been shown that increase of onsd in cases with eicp occurs faster than other ophthalmoscopic findings (16). however, technique, accuracy, and cut off for detecting eicp are different between these studies. girisgin et al. have been shown that mean ond in patients suspected to have eicp is significantly higher than the healthy subjects (17). a similar study on 156 iranian children showed that cases with eicp had significantly larger mean onds (7). we have summarized the results of similar studies in emergency setting or icu in table 2. it seems it is time to determine the best cut off point for detection of eicp in different subgroups of children, adults, cases with different underlying diseases (trauma, cerebrovascular accident and so on), gender, age, and any other important factors which affect the normal or pathologic value of ond and onsd. as other studies have shown, optic nerve sonography has technical limitations and requires a high level of expertise (18). sonography may be impossible to perform because of superficial surgical wounds or severe anatomic alterations in patients with head trauma. moreover, we should consider that bct signs are not always correspond to real elevation of the intracranial pressure. conclusion: sonographic diameter of optic nerve sheath could be considered as an available, accurate, and noninvasive screening tool in determining the elevated intracranial pressure in cases with head trauma or cerebrovascular accident. acknowledgment: we would like to express our special thanks from all cases participated in this study. conflict of interest: there was no conflict of interest. author’s contribution: all authors contribute in drafting/revising the manuscript, study concept or design, analysis or interpretation of data. references: 1. montazeri a. road-traffic-related mortality in iran: a descriptive study. public health. 2004;118(2):110-3. 2. vahedi k, hofmeijer j, juettler e, et al. early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. the lancet neurology. 2007;6(3):215-22. 3. sankhyan n, vykunta raju kn, sharma s, gulati s. management of raised intracranial pressure. indian j pediatr. 2010;77(12):1409–16. 4. tuite gf, chong wk, evanson j, et al. the effectiveness of papilledema as an indicator of raised intracrani al pressure in children with craniosynostosis. neurosurgery. 1996;38(2): 272-8. table 1: basic characteristics of patients characteristics total bct findings p value negative positive age (year) 42.2±19.5 41.9±19.1 44.6±21.8 0.5 gcs 14.8±0.69 14.9±0.37 13.96±1.45 <0.001 left onsd (mm) 4.14±0.77 3.65±0.58 5.5±0.52 <0.001 right onsd (mm) 4.12±0.76 3.9±0.52 5.5±0.7 <0.001 mean onsd (mm) 4.13±0.75 3.9±0.53 5.5±0.56 <0.001 bct: brain computer tomography; gcs: glasgow coma scale; onsd: optic nerve sheath diameter figure 2: receiver operator characteristic (roc) curve at various cut offs of optic nerve sheath diameter. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 18 amini et al table 2: summary of similar studies study sample (n) study population cut off, gold standard sensitivity specificity le et al. usa 2009 (6) 68 cases with suspected or confirmed increased icp, presenting to the ed or icu of an urban, academic, freestanding, tertiary-level children’s hospital, age range: 0-18 years onsd > 4 mm in infants under 1 year onsd > 4.5 mm in children > 1 year ct-scan / ventriculostomy / lumbar puncture 96% 48% kimberly et al. usa 2008 (19) 15 adult patients in both the ed and the neurologic icu who had invasive intracranial monitors placed as part of their clinical care, age > 18 years old onsd > 5 mm invasive intracranial monitors 88% 93% karakitsos et al. greece 2006 (8) 54 patients with brain injury (gcs < 8), mean age ± sd = 40 ±18.6 ond > 5.9 mm ct-scan 74% 65% blaivas et al. usa 2003 (20) 14 ed patients with a suspicion of eicp due to possible focal intracranial pathology, age > 18 years old onsd > 5 mm ct-scan 100% 95% bäuerle et al. germany 2011 (21) 10 patients with idiopathic intracranial hypertension, age ≥18 years old onsd > 5.8 mm measuring the csf opening pressure by lumbar puncture 90% 84% geeraerts et al. france 2008 (22) 37 adult patients requiring sedation and icp monitoring after severe traumatic brain injury, subarachnoid hemorrhage, intracranial hematoma, or stroke, age range: 18–76 years onsd > 5.86 mm invasive measurement icp via a parenchymal device 95% 79% geeraerts et al. uk 2008 (23) 38 patients requiring icp monitoring after severe traumatic brain injury, mean age ± sd = 35 ± 14 onsd > 5.82 mm ct-scan 90% 92% tayal et al. usa 2007 (24) 59 adult ed patients with suspected intracranial injury with possible elevated intracranial pressure without obvious ocular trauma, > 18 years old ond > 5 mm ct-scan 100% 63% soldatos et al. greece 2008 (18) 76 critical care patients, age > 18 years old onsd > 5.7 mm invasive icp measurement using an intraparenchymal catheter 74% 100% major et al. uk 2011 (25) 26 adult patients who required ct from the ed, age > 18 years old onsd > 5 mm ct-scan 86% 100% ed: emergency department, ct: computed tomography, gcs: glasgow coma scale, icp: intracranial pressure, icu: intensive care unit, ond: optic nerve diameter, onsd: optic nerve sheath diameter, mm: millimeter; sd: standard deviation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 19 emergency (2013); 1 (1): 15-19 5. hamilton dr, sargsyan ae, melton sl, et al. sonography for determining the optic nerve sheath diameter with increasing intracranial pressure in a porcine model. j ultrasound med. 2011;30(5):651-9. 6. le a, hoehn me, smith me, spentzas t, schlappy d, pershad j. bedside sonographic measurement of optic nerve sheath diameter as a predictor of increased intracranial pressure in children. ann emerg med. 2009;53(6):785-91. 7. akhavan malayeri a, bavarian s, mehdizadeh m. sonographic evaluation of optic nerve diameter in children with raised intracranial pressure. j ultrasound med. 2005;24(2):143–7. 8. karakitsos d, soldatos t, gouliamos a, et al. transorbital sonographic 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k. validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests. j neurosurg. 1997; 87:34–40. 14. hansen hc, helmke k. the subarachnoid space surrounding the optic nerves. an ultrasound study of the optic nerve sheath. surg radiol anat. 1996;18:323–8. 15. skalka hw. neural and dural optic nerve measurements with a-scan ultrasonography. south med j. 1978;71:399–400. 16. gangemi m, cennamo g, maiuri f, d'andrea f. echographic measurement of the optic nerve in patients with intracranial hypertension. neurochirurgia (stuttg). 1987;30(2):53-5. 17. girisgin as, kalkan e, kocak s, cander b, gul m, semiz m. the role of optic nerve ultrasonography in the diagnosis of elevated intracranial pressure. emerg med j. 2007;24(4):2514. 18. soldatos t, karakitsos d, chatzimichail k, papathanasiou m, gouliamos a, karabinis a. optic nerve sonography in the diagnostic evaluation of adult brain injury. crit care. 2008; 12(3):r67. 19. kimberly hh, shah s, marill k, noble v. correlation of optic nerve sheath diameter with direct measurement of intracranial pressure. acad emerg med. 2008;15(2):201-4. 20. blaivas m, theodoro d, sierzenski pr. elevated intracranial pressure detected by bedside emergency ultrasonography of the optic nerve sheath. acad emerg med. 2003;10(4):37681. 21. bäuerle j, nedelmann m. sonographic assessment of the optic nerve sheath in idiopathic intracranial hypertension. j neurol. 2011;258(11):2014-9. 22. geeraerts t, merceron s, benhamou d, vigué b, duranteau j. non-invasive assessment of intracranial pressure using ocular sonography in neurocritical care patients. intensive care med. 2008;34(11):2062-7. 23. geeraerts t, newcombe vf, coles jp, et al. use of t2weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. crit care. 2008;12(5):r114. 24. tayal vs, neulander m, norton hj, foster t, saunders t, blaivas m. emergency department sonographic measurement of optic nerve sheath diameter to detect findings of increased intracranial pressure in adult head injury patients. ann emerg med. 2007;49(4):508-14. 25. major r, girling s, boyle a. ultrasound measurement of optic nerve sheath diameter in patients with a clinical suspicion of raised intracranial pressure. emerg med j. 2011;28 (8):679-81. emergency. 2017; 5 (1): e33 or i g i n a l re s e a rc h comparing the quality and complications of tube thoracostomy by emergency medicine and surgery residents; a cohort study parvin kashani1, sepideh harati2, ali shirafkan3, alireza amirbeigi4, hamid reza hatamabadi5∗ 1. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3. surgery department, university of texas medical branch, galveston, texas, usa. 4. surgery department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 5. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. received: november 2016; accepted: december 2016; published online: 11 january 2017 abstract: introduction: tube thoracostomy complications depend on the operator’s skill, patients’ general condition and the place in which the procedure is done. the present study aimed to compare the quality and complications of tube thoracostomy carried out by emergency medicine residents (emrs) and surgery residents (srs). methods: this cohort study was conducted on 18-60 years old trauma patients in need of tube thoracostomy presenting to two academic emergency departments. quality of tube placement and its subsequent complications until tube removal were compared between srs and emrs using spss 20. results: 72 patients with the mean age of 37.1±14.1 years were studied (86.1% male). 23 (63.8%) cases were complicated in srs and 22 (61.1%) cases in emrs group (total= 62.5%). chest drain dislodgement (22.2% in srs vs. 22.2% emrs; p>0.99), drainage failure (19.4% in srs vs. 16.7% emrs; p=0.50), and surgical site infection (11.1% in srs vs. 19.4% emrs; p=0.25) were among the most common observed complications. the overall odds ratio of complication development was 0.89 (95% ci: 0.35-2.25, p = 0.814) for srs and 1.12 (95% ci: 0.28-4.53, p = 0.867) for emrs. conclusion: the findings of the present study showed no significant difference between srs and emrs regarding quality of tube thoracostomy placement and its subsequent complications for trauma patients. the rate of complications were interestingly high (>60%) for both groups. keywords: thoracostomy; emergency medicine; general surgery; postoperative complications © copyright (2017) shahid beheshti university of medical sciences cite this article as: kashani p, harati s, shirafkan a, amirbeigi a, hatamabadi h. comparing the quality and complications of tube thoracostomy by emergency medicine and surgery residents; a cohort study. emergency. 2017; 5(1): e33. 1. introduction t ube thoracostomy is one of the most frequent lifesaving interventions in management of trauma patients (1-3). the necessity of tube thoracostomy for traumatic chest injuries has been questioned due to high complication rate reported by some studies (4, 5). tube thoracostomy has the potential to cause complications related to insertion, position and infection. these complica∗corresponding author: hamid reza hatamabadi; emergency department, imam hossein hospital, shahid madani avenue, tehran, iran. tel: +9873432380 e-mail: hhatamabadi@yahoo.com tion rates and types may differ depending on various factors including those related to the patient and the physician (6, 7). tube thoracostomy complications largely depend on the knowledge and skill of the operator in addition to the patients’ general condition and the place in which the procedure is done (8). this procedure has traditionally been performed only by thoracic surgeons and surgery residents (srs). however, in recent years, tube thoracostomy has been performed by other specialties such as emergency medicine residents (emrs) (9-11). ball et al. estimated the prevalence of complications of thoracostomy to be about 13% when done by srs and 40% when done by emrs (12). in iranian emergency medicine curriculum, tube thoracostomy trainthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 2 ing should be provided for all emrs. the present study aimed to compare the quality and complications of tube thoracostomy between emrs and srs of two academic emergency departments. 2. methods 2.1. study design and setting the present cohort study was carried out on trauma patients presenting to the emergency departments of shoahadaye hafte-tir and imam hossein hospitals, tehran, iran, who underwent tube thoracostomy either by srs or emrs. the protocol of the study was approved by the ethics committee of shahid beheshti university of medical sciences. before entering the study, informed written consent was obtained from the patient or their relative. throughout the study, researchers adhered to the principles of helsinki declaration. 2.2. participants study population consisted of 18-60 years old multiple trauma patients who had indication for tube thoracostomy according to the current advanced traumatic life supports (atls) protocol. tube thoracostomy performed in prehospital settings or other centres, patients under 18 or over 60 years old, death for any reason other than those related to thoracostomy, and tube thoracostomy under close observation of attending were considered as exclusion criteria in this study. sampling was performed using convenience method. 2.3. data gathering using a predesigned checklist, patients’ demographic data (age, sex), vital signs (pulse rate, respiratory rate, blood pressure, o2 saturation), indication of tube thoracostomy (pneumothorax, hemothorax, or hemopneumothorax), and quality of tube placement (abutment to mediastinum, extending caudal from insertion site, and intra-fissure/intraabdominal/trans-diaphragmatic placement), as well as complications ( chest drain dislodgement, haemorrhage and vascular injury, empyema and surgical site infection, air leak and subcutaneous emphysema, pulmonary laceration or puncture, and drainage failure) were gathered by one observer resident in each hospital. the observer resident did not interfere with the performed procedure in any stage and only filled out the prepared checklists. the procedures had been performed by third level srs in imam hossein hospital and by third level emrs in hafte-tir hospital. hafte-tir hospital (south tehran) accepts about 250 traumatic patients a day and third level emrs do all the procedures for trauma patients in emergency department but in imam hossein hospital all chest tubes are inserted by srs. after tube thoracostomy, an anterior-posterior chest radiography was performed for all patients and was scored (0 – 5 based on likert scale) regarding the quality of tube placement by two separate radiologists. if any difference was seen in the two reports, a third radiologist was invited. none of radiologists were informed about the patients group. 2.4. outcome the occurrence of one of the above-mentioned complications was considered as primary outcome and quality of tube placement as secondary outcome. all patients were followed until tube thoracostomy removal. 2.5. statistical analysis based on the study by ball et al. the prevalence of complications after tube thoracostomy in srs and emrs groups were 13% and 40%, respectively (12). therefore, considering 95% confidence interval (α=0.05) and 80% power, the minimum sample size required for each group was calculated to be 32 cases. collected data were were analysed using spss software version 20. chi-square test, t-test and fisher-exact test were used for comparing variables between the two groups. with the aim of eliminating probable bias, a backward multifactorial regression logistic model was designed to show the independent effect of residency on the mentioned complications. odds ratios were reported with 95% confidence interval (ci). p-value less than 0.05 was considered as significant. 3. results 3.1. baseline variables 72 patients with the mean age of 37.1±14.1 years were studied (86.1% male). baseline characteristics of participants are summarized in table 1. there was no significant difference between the groups regarding patients’ baseline variables. 3.2. outcome 23 (63.8%) cases of tube thoracostomy were complicated in srs and 22 (61.1%) cases in emrs (total= 62.5%). frequency of tube thoracostomy-related complications in each group is presented in table 2. chest drain dislodgement (22.2% in srs vs. 22.2% emrs; p>0.99), drainage failure (19.4% in srs vs. 16.7% emrs; p=0.50), and surgical site infection (11.1% in srs vs. 19.4% emrs; p=0.25) were among the most common observed complications. the odds ratios for developing tube thoracostomy-related complications are presented in table 3. the overall odds ratio of complication developing was 0.89 (95% ci: 0.35-2.25, p = 0.814) for srs and 1.12 (95% ci: 0.284.53, p = 0.867) for emrs. quality of tube placement was not different between srs and emrs according to radiologist reports (2.5 ± 1.5 versus 2.1 ± 1.3 score, respectively; p=0.19). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e33 table 1: baseline characteristics in the studied groups variable sr (n=36) emr (n=36) p age (year) 35.9±13.8 38.4±14.8 0.46 gender male 31 (86.1) 33 (91.7) 0.71 female 5 (13.9) 3 (8.3) tube thoracostomy indications non-tension pneumothorax 8 (22.2) 13 (36.1) 0.10 hemothorax 15 (41.7) 11 (30.5) 0.63 hemopneumothorax 8 (22.2) 10 (27.8) 0.24 tension pneumothorax 5 (13.8) 2 (5.5) >0.99 accompanying injury brain 6(16.7) 4(11.1) 0.50 spine 4(11.1) 3(8.3) >0.99 neck 2(5.6) 3(8.3) >0.99 chest 10(27.8) 10(27.8) >0.99 pelvic 9(25) 6(16.7) 0.38 upper limb 7 (19.4) 7(19.4) >0.99 lower limb 12(33.3) 5(13.9) 0.05 blood pressure (mmhg) systolic 109.1±18.1 115 ± 18.2 0. 18 diastolic 67.4±8.8 71.1±12.3 0.15 pulse rate (beat/minute) 95.3±12.8 94.0±13.5 0.67 respiratory rate (n/minute) 19.9±3.1 19.3±3.2 0.46 o2 saturation 88.7 ± 3.6 89.2 ± 3.6 0.58 ∗ data are presented as mean ± standard deviation or frequency and percentage. table 2: frequency of tube thoracostomy complications among surgery residents (sr) and emergency medicine residents (emr) complications sr (n=36) emr (n=36) p surgical site infection 4 (11.1) 7 (19.4) 0.25 haemorrhage1 2 (5.6) 0 (0.0) 0.24 pulmonary laceration 1 (2.8) 1 (2.8) 0.75 drain dislodgement 8 (22.2) 8 (22.2) >0.99 subcutaneous emphysema 2 1 (2.8) 0 (0.0) >0.50 drainage failure 7 (19.4) 6(16.7) 0.50 ∗ data were presented as number and percentage.1: due to vascular injury, 2: air leak. 4. discussion the findings of the present study showed no significant difference between srs and emrs regarding quality of tube thoracostomy placement and its subsequent complications for trauma patients. the prevalence of tube thoracostomy complications were 63.8% and 61.1% in srs and emrs, respectively (total= 62.5%). the rate of intercostal artery injury, pleural cavity infection, and retroperitoneal placement of tube thoracostomy was reported to be 37% in sethuraman et al. study. they revealed that, tube thoracostomy by emrs has similar complication rates as the other residents and they are generally minor types of complications (13). aziz et al., in a year-long study in 2010, showed that operator’s skill is one of the most important factors affecting the outcome and complications of tube thoracostomy placement. the complication rates were exceptionally higher if residents did the procedure compared to the specialists. they reported the 36.7% total complication rate consisted of 26.7% technical and 10% infective (14). total complication rates in the present study were higher than others reports (about 2 times). this higher prevalence rate might be due to lack of knowledge, proper attitude or skills among the studied residents regarding tube thoracostomy. therefore, holding continuous training courses and performing the procedure under supervision of a specialist may be effective in this regard. chan et al. did a retrospective study in 1997 and revealed that tube thoracostomy placement in the emergency department does not lead to a higher rate of complication compared to tube insertion in the operating room (15). ball et al. also did a retrospective study and revealed 88% technical and 12% infective complications. additionally, tube placements by nonsurgery residents outside the trauma wards were the independent prognostic factors for occurrence of complications. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 4 table 3: the odds ratio for developing tube thoracostomy-related complications among surgery residents (sr) and emergency medicine residents (emr) complication odds ratio (95% ci)* p value overall sr 0.89 (0.35-2.25) 0.814 emr 1.12 (0.28-4.53) 0.867 surgical site infection sr 0.52 (0.14-1.95) 0.311 emr 0.65 (0.12-3.63) 0.621 pulmonary laceration sr 1.00 (0.60-16.62) 1.000 emr 0.00 0.998 drain dislodgement sr 1.00 (0.33-3.04) 1.000 emr 1.10 (0.24-5.04) 0.895 drainage failure sr 1.20 (0.36-4.02) 0.760 emr 2.23 (0.47-10.61) 0.310 ∗ : not applicable for haemorrhage and subcutaneous emphysema; ci: confidence interval. 13% of the tubes placed by srs and 40% of the tubes placed by emrs had complications (12). it is strongly suggested to enhance the quality of education starting with a kap study (knowledge, attitude, and practice) on srs and emrs regarding placement of tube thoracostomy. 5. limitation carrying out the study in 2 separate centres, and therefore having different conditions in the emergency departments regarding staff, patients and environment, might have prevented fully considering/adhering to characteristics of a cohort among participants, especially regarding selection bias. in addition, not blinding the observer residents might lead to observer bias. among other limitations of this study is its small sample size. 6. conclusion the findings of the present study showed no significant difference between srs and emrs regarding quality of tube thoracostomy placement and its subsequent complications for trauma patients. the rate of complications were interestingly high (>60%) for both groups. 7. appendix 7.1. acknowledgements the authors wish to acknowledge the cooperation of imam hossein and hafte-tir emergency departments’ staff. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support this research has been supported by sina trauma and surgery research center, tehran university of medical sciences. 7.4. conflict of interest the authors report no declarations of interest. references 1. forouzanfar mm, safari s, niazazari m, baratloo a, hashemi b, hatamabadi hr, et al. clinical decision rule to prevent unnecessary chest x-ray in patients with blunt multiple traumas. emergency medicine australasia. 2014;26(6):561-6. 2. safari s, baratloo a, negida as, taheri ms, hashemi b, selkisari sh. comparing the interpretation of traumatic chest x-ray by emergency medicine specialists and radiologists. 2014. 3. paydar s, moghaninasab a, asiaei e, sabetian fard jahromi g, bolandparvaz s, abbasi h. outcome of patients underwent emergency department thoracotomy and its predictive factors. emergency. 2014;2(3):125-9. 4. menger r, telford g, kim p, bergey mr, foreman j, sarani b, et al. complications following thoracic trauma managed with tube thoracostomy. injury. 2012;43(1):46-50. 5. bailey r. complications of tube thoracostomy in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e33 trauma. journal of accident & emergency medicine. 2000;17(2):111-4. 6. collop na, kim s, sahn sa. analysis of tube thoracostomy performed by pulmonologists at a teaching hospital. chest journal. 1997;112(3):709-13. 7. cho dy, sohn ds, cheon yj, hong k. complications of a tube thoracostomy performed by emergency medicine residents. journal of the korean society of traumatology. 2012;25(2):37-43. 8. mancini mc. blunt chest trauma. ingles) thoracic surgery emedicine com consultado el. 2012;30. 9. sirleaf m, jefferson b, christmas ab, sing rf, thomason mh, huynh tt. comparison of procedural complications between resident physicians and advanced clinical providers. journal of trauma and acute care surgery. 2014;77(1):143-7. 10. dural k, gulbahar g, kocer b, sakinci u. research article a novel and safe technique in closed tube thoracostomy. 2010. 11. safari s, baratloo a, negida as, taheri ms, hashemi b, selkisari sh. comparing the interpretation of traumatic chest x-ray by emergency medicine specialists and radiologists. archives of trauma research. 2014;3(4). 12. ball cg, lord j, laupland kb, gmora s, mulloy rh, ng ak, et al. chest tube complications: how well are we training our residents? canadian journal of surgery. 2007;50(6):450-8. 13. sethuraman kn, duong d, mehta s, director t, crawford d, st george j, et al. complications of tube thoracostomy placement in the emergency department. the journal of emergency medicine. 2011;40(1):14-20. 14. aziz a, pirzada mt, haider j, alam sn, malik ka. complications of tube thoracostomy in isolated chest injuries. journal of surgery pakistan (international). 2010;15(3):126. 15. chan l, reilly km, henderson c, kahn f, salluzzo rf. complication rates of tube thoracostomy. the american journal of emergency medicine. 1997;15(4):368-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e31 or i g i n a l re s e a rc h worthing physiological score vs revised trauma score in outcome prediction of trauma patients; a comparative study babak nakhjavan-shahraki1, mahmoud yousefifard2, mohammad javad hajighanbari3, parviz karimi4, masoud baikpour5, jalaledin mirzay razaz6, mehdi yaseri7, kavous shahsavari8, fatemeh mahdizadeh9, mostafa hosseini7∗ 1. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. 2. physiology research center and department of physiology, faculty of medicine, iran university of medical sciences, tehran, iran. 3. department of emergency medicine, hafte tir hospital, iran university of medical sciences, tehran, iran. 4. department of emergency medicine, robatkarim hospital, iran university of medical sciences, tehran, iran. 5. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 6. department of community nutrition, faculty of nutrition and food technology, shahid beheshti university of medical sciences, tehran, iran. 7. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 8. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. 9. department of emergency medicine, ilan university of medical sciences, ilam, iran. received: october 2016; accepted: november 2016; published online: 11 january 2017 abstract: introduction: awareness about the outcome of trauma patients in the emergency department (ed) has become a topic of interest. accordingly, the present study aimed to compare the rapid trauma score (rts) and worthing physiological scoring system (wpss) in predicting in-hospital mortality and poor outcome of trauma patients. methods: in this comparative study trauma patients brought to five eds in different cities of iran during the year 2016 were included. after data collection, discriminatory power and calibration of the models were assessed and compared using stata 11. results: 2148 patients with the mean age of 39.50±17.27 years were included (75.56% males). the auc of rts and wpss models for prediction of mortality were 0.86 (95% ci: 0.82-0.90) and 0.91 (95% ci: 0.87-0.94), respectively (p=0.006). rts had a sensitivity of 71.54 (95% ci: 62.59-79.13) and a specificity of 97.38 (95% ci: 96.56-98.01) in prediction of mortality. these measures for the wpss were 87.80 (95% ci: 80.38-92.78) and 83.45 (95% ci: 81.75-85.04), respectively. the auc of rts and wpss in predicting poor outcome were 0.81 (95% ci: 0.77-0.85) and 0.89 (95% ci: 0.85-0.92), respectively (p<0.0001). conclusion: the findings showed a higher prognostic value for the wpss model in predicting mortality and severe disabilities in trauma patients compared to the rts model. both models had good overall performance in prediction of mortality and poor outcome. keywords: trauma severity indices; prognosis; trauma; emergency department; decision support techniques © copyright (2017) shahid beheshti university of medical sciences cite this article as: nakhjavan-shahraki b, yousefifard m, hajighanbari m, karimi p, baikpour m, mirzay razaz j, yaseri m, s, shahsavari k, mahdizadeh f, hosseini m. worthing physiological score vs revised trauma score in outcome prediction of trauma patients; a comparative study. emergency. 2017; 5(1): e31. ∗corresponding author: mostafa hosseini, department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 2 1. introduction q uick assessment of trauma patients and knowledge about the severity of their injuries can significantly affect the outcome of these patients, decrease their mortality rates and their associated disabilities (1-7). awareness about the final outcome of trauma patients in the emergency setting has become a topic of discussion in recent years and various methods have been proposed to address this issue. in this regard, different scoring systems have been developed (8-10). over the years these scoring systems became so popular among physicians that encouraged further development of these models. application of these scoring systems help in identifying high-risk patients (9), which leads to a better controlled management and treatment of patients. nevertheless, each of these scoring systems have their own shortcomings, some of which include numerous variables involved in the model, complicated calculations needed to reach a conclusion (e.g. injury severity score) and their validity and reliability not having been assessed in different clinical settings. these limitation encouraged researchers to design better systems, the examples of which are the revised trauma score (rts), rapid acute physiology score (raps), rapid emergency medicine score (rems) and worthing physiological scoring system (wpss) (11-14). rts is a scoring system based on physiologic variables of glasgow coma scale (gcs), systolic blood pressure (sbp) and respiratory rate (rr), in which the gcs has higher weight compared to the other two variables. however, its low prognostic value for outcome of trauma patients pushed the researchers to search for other scoring systems (12, 14). wpss was another scoring system presented in the year 2007. the model was designed based on a study conducted on 3184 patients that found the 6 factors of rr, pulse rate, sbp, body temperature, the oxygen saturation and the level of consciousness assessed on arrival of the patients to be able to predict their mortality (11). however, little information is available on the overall validity of this model. accordingly, the present study was designed to assess and compared the value of wpss and rts models in prediction of in-hospital mortality and poor outcome in trauma patients presenting to the emergency departments. 2. methods 2.1. study design and setting in this prospective cross-sectional study, trauma patients brought to five emergency departments in different cities +982188989125; fax: +982188989127 table 1: baseline characteristics of studied patients variable value age (year) 39.50 ± 17.27 gender(n, %) male 1623 (75.56) female 525 (24.44) trauma mechanism motorcycle accident 591 (27.51) car rider accident 518 (24.12) pedestrian 378 (17.60) falls more than 3 meters 152 (7.08) falls less than 3 meters 201 (9.36) other 308 (14.34) gcs 14.4 ± 2.19 hr (beat/minute) 87.60 ± 15.63 sbp (mmhg) 115.38 ± 15.36 dbp (mmhg) 73.49 ± 10.07 o2 saturation 94.78 ± 5.80 temperature (celsius) 36.81 ± 0.90 rr (number/minute) 16.46 ± 6.15 outcome good recovery 1630 (75.88) moderate disability 342 (15.92) severe disability 53 (2.47) death 123 (5.73) data were presented as mean ± standard deviation or frequency and percentage; gcs: glasgow coma scale; hr: heart rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; o2 saturation: arterial oxygen saturation; rr: respiratory rate. of iran (tehran, ilam, jahrom, tabriz and urmia) from may to october 2016 were included. completed checklists were posted to tehran and reviewed by the senior researcher. after verifying their validity, gathered data were analyzed using the statistical software. the ethics committee of tehran university of medical sciences reviewed and approved the study protocol. the guidelines laid down by declaration of helsinki were adhered to by all the authors throughout the survey and all the included patients or their family members signed an informed written consent for participating in the study. 2.2. participants trauma patients older than 18 years of age brought to the designated emergency departments were included as the study population through a convenience sampling method. pregnancy and death before admission to the emergency department were considered as the exclusion criteria. 2.3. data gathering gathered information included age, gender, trauma mechanism, vital signs, arterial oxygen saturation level, and level of consciousness on admission. the patients were followed throughout their hospital stay and their final outcome (exthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e31 figure 1: area under the curve (auc) of revised trauma score (rts) and worthing physiological scoring system (wpss) in prediction of inhospital mortality and poor outcome. pired vs. alive) along with the condition in which the patient was discharged from the hospital (full recovery, moderate disability, severe disability or vegetative state) were recorded. 2.4. assessed outcomes glasgow outcome scale (gos) was used to assess the final outcome of the patient when being discharged from the hospital (20). in-hospital mortality was considered as the primary outcome and discharge with a severe disability (based on gos) was considered as the secondary outcome. 2.5. statistical analysis in order to calculate the minimum sample size needed for this survey, the rate of in-hospital mortality in trauma patients was considered as 5.2% based on previous reports (21). accordingly, the minimum sample size was estimated at 1894 patients based on a 95% confidence interval (ci) (α=0.05), a 90% power (β=0.1) and a maximum error of 1.5% (d=0.015). data analysis was performed by stata 11.0 software. severity of trauma were calculated for each patient based on rts and wpss models and the prognostic value of the systems was compared according to the discrimination power, calibration and overall performance. discrimination was evaluated by measuring the area under the curve (auc) of the receiver operating characteristic (roc) curve and calculating the sensitivity, specificity, positive and negative likelihood ratios with 95% ci. the method proposed by cleves and rick was used for comparing auc for the two models (22). calibration plot was constructed for assessment of general calibration in which the frequency of observed versus predicted mortality or poor outcome were compared. overall performance was assessed by evaluating the predictive reliability and predictive accuracy based on the calculated brier score. finally, in order to assess the concordance between rts-predicted and wpss-predicted percent of mortality and poor outcome, spearman’s rank coefficient was computed. a p value less than 0.05 was considered as statistically significance level in all analyses. 3. results a total of 2148 patients with the mean age of 39.50±17.27 year were included in this survey (75.56% male). motorcycle accident was the most common trauma mechanism (75.65%). gcs ranged from 3-8 in 63 patients (2.98%), 9-12 in 36 patients (1.7%) and it was higher than 13 in 2014 cases (95.3%). table 1 presents the basic characteristics of the studied subjects. follow up of the subjects revealed that only 2.47% of the patients were discharged with severe disabilities and 5.73% of the cases expired. 3.1. performance of rts and wpss in prediction of mortality 3.1.1. discrimination the auc of the two rts and wpss models for prediction of patients’ mortality was calculated to be 0.86 (95% ci: 0.820.90) and 0.91 (95% ci: 0.87-0.94), respectively (p=0.006). the optimum cut-off level was found to be 1 for the rts and 4 for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 4 figure 2: calibration plots of revised trauma score (rts) and worthing physiological scoring system (wpss) in prediction of in-hospital mortality and poor outcome. the wpss. the sensitivity and specificity of the rts model for predicting patients’ mortality was calculated to be 71.54 (95% ci: 62.59-79.13) and 97.38 (95% ci: 96.56-98.01), respectively. these measures for the wpss were found to be 87.80 (95% ci: 80.38-92.78) and 83.45 (95% ci: 81.75-85.04), respectively (figure 1 and table 2). 3.1.2. calibration both scoring systems had good calibration (agreement between observed and predicted rate of mortality) in prediction of mortality. calibration plot of the rts model had a slope of 1.04 and an intercept of 0.02. the mentioned measured were calculated to be 1.02 and 0.01 for the wpss model, respectively (figure 2). 3.1.3. overall performance brier score and scaled reliability of the rts model in prediction of mortality were 0.024 and zero, respectively. these measures were found to be 0.031 and 0.0003 for the wpss model, respectively. the findings exhibit the high predictive accuracy and reliability of both models (table 3). 3.2. performance of rts and wpss in prediction of poor outcome 3.2.1. discrimination the rts model had an auc of 0.81 (95% ci: 0.77-0.85) in predicting poor outcome, which was significantly lower than that of wpss model with an auc of 0.89 (95% ci: 0.85-0.92) (p<0.0001). the sensitivity and specificity of the rts model for predicting poor outcome was found to be 61.93 (95% ci: 54.29-69.05) and 98.38 (95% ci: 97.69-98.87) considering the cut-off value of 1, respectively. these figures for the wpss model with a cut-off level of 4 were calculated to be 82.95 (95% ci: 76.40-88.03) and 84.95 (95% ci: 83.27-86.47), respectively (figure 1 and table 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e31 figure 3: concordance between revised trauma score (rts) predicted and worthing physiological scoring system (wpss) predicted percent of mortality and poor outcome. table 2: screening performance characteristics of revised trauma score (rts) and worthing physiological scoring system (wpss) in prediction of mortality and poor outcome characteristics mortality poor outcome rts wpss rts wpss true positive 88 108 109 146 true negative 1972 1690 1940 1675 false positive 53 335 32 297 false negative 35 15 67 30 sensitivity 71.54 (62.59-79.13) 87.80 (80.38-92.78) 61.93 (54.29-69.05) 82.95 (76.40-88.03) specificity 97.38 (96.56-98.01) 83.45 (81.75-85.04) 98.38 (97.69-98.87) 84.94 (83.27-86.47) positivelr 27.34 (20.49-36.46) 5.31 (4.72-5.97) 38.16 (28.56-54.85) 5.51 (4.86-6.24) negative lr 0.29 (0.22-0.39) 0.15 (0.09-0.24) 0.39 (0.32-0.47) 0.20 (0.14-0.28) ∗ data are presented as estimated value and 95% confidence interval. lr: likelihood ratio. table 3: overall performance of revised trauma score (rts) and worthing physiological scoring system (wpss) in prediction of in-hospital mortality and poor outcome characteristics mortality poor outcome rts wpss rts wpss brier score 0.026 0.031 0.038 0.045 scaled reliability <0.0001 0.0003 <0.0001 0.001 3.2.2. calibration both scoring systems had good calibration in predicting poor outcome of patients as well. the slope and intercept of the rts model’s calibration plot were 1.05 and 0.04, respectively. the mentioned measures were 0.87 and 0.01 for the wpss model’s calibration plot (figure 2). 3.2.3. overall performance brier score and scaled reliability calculated for rts model in predicting patients’ poor outcome were 0.034 and zero, while these measures were found to be 0.045 and 0.001 for the wpss model, respectively (table 3). both rts and wpss models have good overall performance in prediction of poor outcome. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 6 3.3. concordance between rts and wpss there was good concordance between rts and wpss models in prediction of mortality (r=0.63; p <0.001) and poor outcome (r=0.68; p <0.001) (figure 3). 4. discussion: classifying the severity of trauma in emergency settings is a challenging issue for the physicians. scoring system can help to diagnosis of high risk patient. however, each scoring systems have specific advantages and limitations. the present study compared the two physiologic scoring systems of rts and wpss and found that the value of wpss model in predicting mortality and occurrence of severe disabilities in trauma patients in higher than that of the rts model. although the rts model involves simple criteria for estimating the severity of injuries, its prognostic value is at a moderate level. an acceptable scoring system for prediction of an outcome should have a high screening value along with a high sensitivity. the sensitivity of rts model in prediction of mortality and poor outcome were 71.54% and 61.93%, respectively, while similar figures for the wpss model were found to be 82.95% and 87.8%. despite the greater number of variables included in the wpss model compared to rts model, its application is easy (11). wpss is a physiologic scoring system which incorporates the respiratory rate, pulse rate, body temperature, arterial oxygen saturation and the level of consciousness. these factors can be easily assessed and are routinely evaluated in the emergency departments. the only factor that is not precisely measured in the emergency settings is the body temperature. in the busy hours of an emergency department, physicians or nurses might not pay adequate attention to accurate measuring of the patients’ body temperature, while assessment of this factor plays an important role in predicting the outcome of patients. therefore, it is suggested that more attention be paid to the body temperature as a physiologic factor in patients referring to emergency departments. few studies have assessed the prognostic value of wpss for patients’ mortality. the findings of the present survey is congruent with the results of the study conducted by duckitt et al. which has shown that the wpss model is a better index for predicting patients’ mortality compared to the early-warning scoring system (11). ha et al. also reported that both rapid emergency medicine score and wpss have good prognostic values for mortality of patients in the emergency department, with the latter slightly superior to the former scoring system (23). similarly, brabrand et al. referred to the wpss model as a scoring system with acceptable discriminatory power and calibration in predicting patients’ mortality (24). in this regard, it seems that the wpss model can be used as a screening tool for classifying trauma patients in the emergency departments. the large sample size of the present study and its multi-center setting could be considered as the strengths of this survey warranting its power. moreover, the results of this study can be generalized to the whole iranian population since patients were included from emergency departments located in five different cities of tehran, ilam, jahrom, tabriz and urmia. 5. limitations the findings might be subject to selection bias due to the convenience sampling method used for inclusion of patients. another factor that might have confounded the results of this survey was the probably inaccurate measurement of the patients’ axillary body temperature in the overcrowded emergency departments. 6. conclusion the findings showed a higher prognostic value for the 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scale: an inter-rater reliability study. brain injury. 1993;7(4):309-17. 21. imhoff bf, thompson nj, hastings ma, nazir n, moncure m, cannon cm. rapid emergency medicine score (rems) in the trauma population: a retrospective study. bmj open. 2014;4(5). 22. cleves ma, rock l. from the help desk: comparing areas under receiver operating characteristic curves from two or more probit or logit models. the stata journal. 2002;2(3):301-13. 23. ha dt, dang tq, tran nv, vo ny, nguyen nd, nguyen tv. prognostic performance of the rapid emergency medicine score (rems) and worthing physiological scoring system (wps) in emergency department. international journal of emergency medicine. 2015;8(1):18. 24. brabrand m, hallas j, knudsen t. nurses and physicians in a medical admission unit can accurately predict mortality of acutely admitted patients: a prospective cohort study. plos one. 2014;9(7):e101739. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion: limitations conclusion appendix references emergency. 2017; 5 (1): e15 or i g i n a l re s e a rc h ability of ultrasonography in detection of different extremity bone fractures; a case series study farzad bozorgi1, massoud shayesteh azar2, seyed hossein montazer1, aroona chabra3, seyed farshad heidari1∗, alireza khalilian4 1. department of emergency medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran. 2. orthopedic research center, faculty of medicine, mazandaran university of medical sciences, sari, iran. 3. student research committee, faculty of pharmacy, mazandaran university of medical sciences, sari, iran. 4. department of statistics, faculty of medicine, mazandaran university of medical sciences, sari, iran. received: june 2016; accepted: july 2016; published online: 9 january 2017 abstract: introduction: despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several potential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible, and ability to be used on the bedside. the aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. methods: this study is a case series study, which was prospectively conducted on multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture. after initial assessment, ultrasonography of suspected bones was performed by a trained emergency medicine resident and prevalence of true positive and false negative findings were calculated compared to plain radiology. results: 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). analysis was done on 158 sites of fracture, which were confirmed with plain radiography. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. the most frequent site of injuries were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. prevalence of true positive and false negative cases for fractures detected by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. in addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. conclusion: the present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. it had low sensitivity in detection of in intra-articular fractures. keywords: ultrasonography; radiography; fractures, bone; diagnosis; emergency service, hospital © copyright (2016) shahid beheshti university of medical sciences cite this article as: bozorgi f, shayesteh azar m, montazer s-h, chabra a, heidari s-f, khalilian a. ability of ultrasonography in detection of different extremity bone fractures; a case series study. emergency. 2017; 5 (1): e15. 1. introduction orthopedic injuries, including bone fractures are widespread and cause a large portion of emergency department (ed) visits. among them, extremity injuries are frequent and result in approximately 3.5% of annual ed visits all over the world (1). plain radiography is the ordinary standard of care for ∗corresponding author: seyed farshad heidari; department of emergency medicine, emam khomeini hospital, sari, iran. tel: +981133355080, fax: +981133364044 e-mail: s.f.heidari@gmail.com evaluation and diagnosis of long bone fractures (2). however, it could result in unnecessary radiation exposure to patients, especially children with tissues sensitive to radiation and pregnant women (3, 4). the risk of transferring critical patients to the radiography unit is another concern and it may not even be available in some areas (2, 5). therefore, finding safer, economic, and readily available alternative imaging techniques is a matter of interest. the use of ultrasonography in both ed and pre-hospital settings has increased significantly over the last decade (6, 7). despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several pothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. bozorgi et al. 2 tential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible and affordable, and ability to be used on the bedside (2, 5, 8-10). it has been shown to be able to recognize occult fractures indiscernible on plain radiographs (11, 12). ultrasonography can be performed during clinical examination, which may help in more rapid and accurate decision making (13, 14). the aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. 2. methods 2.1. study design this study is a case series study, which evaluates the diagnostic accuracy of ultrasonography in detection of extremity bones fractures. the duration of the study was one year, from june 2014 to may 2015, and trauma patients presenting to the ed of imam khomeini hospital, sari, iran, complaining of painful extremities were evaluated. the protocol of study was approved by the local ethics committee of mazandaran university of medical sciences and authors adhered to principles of helsinki declaration and confidentiality of patient information during the study period. written informed consent was obtained from all patients before inclusion in the study. 2.2. participants multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture were prospectively enrolled. patients, who had been carried to the operating room emergently, had decreased level of consciousness and evidence of open fractures were excluded. 2.3. procedure an emergency medicine physician, who completed a 3-months musculoskeletal ultrasonography educational course, was responsible for initial examination and performing bedside ultrasonography for all of the participants. he performed bedside ultrasonography on upper and lower extremity bones with particular punctuality over the areas with maximum pain or tenderness. ultrasonography was performed in longitudinal and transverse planes in supine position prior to obtaining plain radiographs. a portable ultrasonography device (sonoace r3 system, samsung, south korea) with a high frequency (10 to 15 mhz) broadband linear array transducer was used for screening bone fractures. considering the large muscle bulk, ultrasonography of femur bones was performed with deep array transducer. abnormalities of the cortex including a break, step-off, or discontinuity of the cortical margin at the fracture site were considered as ultrasonographic signs of fracture. after initial assessment of patients according to advanced trauma life support (atls) guidelines, ultrasonography of long bones suspected to fracture was done and in cases of positive findings, reduction, traction, and splinting was done and the patients were referred to the radiography unit for imaging (anterior-posterior (ap), lateral and oblique views (if indicated)). after performing standard radiography, radiography images were interpreted by an orthopedic specialist blinded to ultrasonography and clinical findings. in cases with high clinical suspicion for fracture, whose findings of plain radiography was uncertain, computed tomography (ct) scan was performed. demographic data as well as ultrasonography and radiography findings were gathered using a predesigned checklist. 2.4. statistical analysis statistical analyses were carried out with spss version 18. qualitative data were presented as frequency and percentage, and quantitative ones as mean ± standard deviation. prevalence of true positive and false negative results of ultrasonography in detection of extremity fractures compared to radiography (as the gold standard) was calculated. table 1: characteristics of fractures in studied patients variables frequency (%) upper extremity humerus 21 (13.30) radius 40 (25.31) ulna 18 (11.40) metacarpus 12 (7.6) lower extremity femur 30 (19.00) tibia 23 (14.55) fibula 11 (6.97) metatarsus 3 (1.8) location proximal 37 (23.4) middle 42 (26.5) distal 79 (50.0) side left 70 (44.3) right 88 (55.7) number 1 73 (67.6) ≥ 2 35 (32.4) intra-articular yes 50 (31.6) no 108 (68.4) 3. results: 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). neither radiography nor ultrasonography showed any fractures in three patients, but considerthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e15 table 2: characteristics of ultrasonography in detection of different extremity bone fractures fracture site true positive n (%) false negative n (%) humerus 16 (76.2) 5 (23.8) radius 29 (72.5) 11 (27.5) ulnar 9 (50) 9 (50) metacarpus 5 (41.7) 7 (58.3) femur 30 (100) 0 (0) tibia 10 (43.5) 13 (56.5) fibula 8 (72.7) 3 (27.3) metatarsus 1 (33.3) 2 (66.4) ing continuous pain, tenderness and limited range of motion, they underwent ct scan, which confirmed fracture of tibial plateau, distal femur, and radius head. finally, analyses were done on 158 sites of fracture, which were confirmed by plain radiography. table-1 shows the type and distributions of fractures. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. the most frequent sites of injury were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. 99 (62.7%) cases of fracture were dislocated and 50 (31%) were intra-articular. table 2 shows characteristics of ultrasonography in detection of different upper and lower extremity bone fractures. prevalence of true positive and false negative detected cases for fractures by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. in addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. 4. discussion: the present study showed the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. it had low sensitivity in detection of in intraarticular extremity bone fractures. ultrasonography application is rising in all aspects of diagnostic studies. it seems to be secure and reliable, and is being used increasingly for diagnostic evaluations in ed (15). previous studies have shown that bedside ultrasonography by trained clinicians is as impressive as radiography for diagnosis of long bone fractures. patel et al. showed that ultrasonography is as useful as radiography for diagnosis of long bone fractures, and has a high sensitivity for diagnosis of such fractures(16). haddadzebouni et al. showed the high accuracy of bedside ultrasonography for diagnosis of bone fractures and recommended ultrasonography for this propose(17). hubner et al. also found that diagnosis of long bone fractures using ultrasonography is accurate in majority of cases (8). some studies have shown that ultrasonography is more useful than radiography in diagnosis of fracture in some cases that perhaps were not detected in radiographic imaging such as hip, clavicle, knees and feet (12, 16). in contrast, bolandparvaz et al. showed that ultrasonography was not reliable and adequate for diagnosis of long bone fractures(18). majority of studies in this regard have been conducted on pediatrics population (8, 17, 19). bolandparvaz et al. and marshburn et al. concluded that ultrasonography is reliable only when an injury cannot be detected by radiography and showed that specificity of ultrasonography is not high enough for confirmation of long bone fractures in adults (5, 18). based on the results of the present study, it seems that, ultrasonography could not be considered as an accurate screening tool for detection of extremity fractures in the adult population. more studies are required to infer the role of ultrasonography in detection of bone fractures in trauma guidelines. low sample size and lack of control group are two important limitations of the present study, which undermine the generalizability of the results. 5. conclusion: the present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. it had low sensitivity in detection of in intraarticular extremity bone fractures. 6. appendix 6.1. acknowledgements the contribution of all ed staff of imam khomeini hospital, sari, is appreciated. 6.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. bozorgi et al. 4 6.3. conflict of interest none. 6.4. funding none. references 1. mccaig lf, nawar ew. national hospital ambulatory medical care survey: 2004 emergency department summary: us department of health and human services, centers for disease control and prevention, national center for health statistics; 2006. 2. cross kp. bedside ultrasound for pediatric long bone fractures. clinical pediatric emergency medicine. 2011;12(1):27-36. 3. donnelly lf. reducing radiation dose associated with pediatric ct by decreasing unnecessary examinations. american journal of roentgenology. 2005;184(2):655-7. 4. watson n, ferrier g. diagnosis of femoral shaft fracture in pregnancy by ultrasound. journal of accident & emergency medicine. 1999;16(5):380. 5. marshburn th, legome e, sargsyan a, li smj, noble va, dulchavsky sa, et al. goal-directed ultrasound in the detection of long-bone fractures. journal of trauma and acute care surgery. 2004;57(2):329-32. 6. tirado a, wu t, noble ve, huang c, lewiss re, martin ja, et al. ultrasound-guided procedures in the emergency departmentâăťdiagnostic and therapeutic asset. emergency medicine clinics of north america. 2013;31(1):11749. 7. heegaard w, hildebrandt d, spear d, chason k, nelson b, ho j. prehospital ultrasound by paramedics: results of field trial. academic emergency medicine. 2010;17(6):624-30. 8. hubner u, schlicht w, outzen s, barthel m, halsband h. ultrasound in the diagnosis of fractures in children. bone & joint journal. 2000;82(8):1170-3. 9. saul t, ng l, lewiss re. point-of-care ultrasound in the diagnosis of upper extremity fracture-dislocation. a pictorial essay. medical ultrasonography. 2013;15(3):230. 10. blankstein a. ultrasound in the diagnosis of clinical orthopedics: the orthopedic stethoscope. world j orthop. 2011;2(2):13-24. 11. patten rm, mack la, wang ky, lingel j. nondisplaced fractures of the greater tuberosity of the humerus: sonographic detection. radiology. 1992;182(1):201-4. 12. wang cl, shieh jy, wang tg, hsieh fj. sonographic detection of occult fractures in the foot and ankle. journal of clinical ultrasound. 1999;27(8):421-5. 13. wakefield rj, balint pv, szkudlarek m, filippucci e, backhaus m, d’agostino m-a, et al. musculoskeletal ultrasound including definitions for ultrasonographic pathology. the journal of rheumatology. 2005;32(12):2485-7. 14. geusens e, pans s, van breuseghem i, brys p. ultrasound in acute trauma of the ankle and hindfoot. emergency radiology. 2002;9(5):283-8. 15. stahmer sa. accident and emergency medicine. british medical journal. 1998;316(7137):1071. 16. patel dd, blumberg sm, crain ef. the utility of bedside ultrasonography in identifying fractures and guiding fracture reduction in children. pediatric emergency care. 2009;25(4):221-5. 17. haddad-zebouni s, khalil sa, roukos s, menassamoussa l, smayra t, aoun n, et al. musculoskeletal imaging-limb fractures: ultrasound imaging features. journal de radiologie. 2008;89(5-c1):557-63. 18. bolandparvaz s, moharamzadeh p, jamali k, pouraghaei m, fadaie m, sefidbakht s, et al. comparing diagnostic accuracy of bedside ultrasound and radiography for bone fracture screening in multiple trauma patients at the ed. the american journal of emergency medicine. 2013;31(11):1583-5. 19. chen l, kim y, moore cl. diagnosis and guided reduction of forearm fractures in children using bedside ultrasound. pediatric emergency care. 2007;23(8):528-31. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e12 ca s e re p o rt a 25-year-old chronic ketamine user with urinary symptoms; a case report chin-chu wu1, aming chor-ming lin2,3∗ 1. department of medical imaging, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. school of medicine, fu-jen catholic university, new taipei city, taiwan. received: december 2021; accepted: december 2021; published online: 31 january 2022 abstract: ketamine is mainly used for short-acting general anesthesia, chronic pain, sedation, depression, and bipolar disorder. long-term ketamine use may cause lower urinary tract symptoms and voiding dysfunction. small capacity and fibrotic bladder can be associated with chronic ketamine use. here, we present a 25-year-old male with a history of chronic ketamine use complicated with contracted heart-shape bladder. keywords: tomography, x-ray computed; ketamine; urologic diseases; urinary tract infections cite this article as: wu cc, lin acm. a 25-year-old chronic ketamine user with urinary symptoms; a case report. arch acad emerg med. 2022; 10(1): e12. https://doi.org/10.22037/aaem.v10i1.1449. 1. introduction sustained ketamine use results in small capacity, and fibrotic and contracted bladder, which can lead to damage to the urinary tract system. the clinical presentations range from suprapubic pain, small volume voids, and irritative lower tract symptoms to painful hematuria. long-term abusers with a small and fibrotic bladder and poor compliance are at high risk for complications including hydronephrosis, vesicoureteral reflux, urolithiasis, chronic renal failure, and recurrent urinary tract infections (1). we herein report a case of chronic ketamine use, complicated with contracted bladder with a heart-shape appearance on computed tomography (ct) scan. 2. case presentation a 25-year-old man presented to the emergency department with complaint of fever, urinary frequency, dysuria, bilateral dull flank pain, and unspecific abdominal pain for one week. he had a history of bipolar disorder and chronic ketamine use. on arrival, his blood pressure was 138/82 mmhg, with ∗corresponding author: aming chor-ming lin; emergency department, shin kong wu ho-su memorial hospital, 95 wen chang rd, shih lin district, taipei 111 taiwan. tel: 886-02-28332211 ext 2082, fax: 886-02-28353547, e-mail: m002001@ms.skh.org.tw, orcid: http://orcid.org/0000-0002-38427216. a heart rate of 101 beats/minute, a respiratory rate of 20 beats/minute, and oxygen saturation of 98% on room air. his temperature was 38.2 °c. on physical examination, the patient had lower abdominal tenderness and bilateral flank knocking pain. the rest of physical examination were unremarkable. the complete blood cell count showed the following results: leukocyte count 14500/mm3 with 92% of segmented neutrophils, hemoglobin 10.8 gram/deciliter, platelet 520000/microliter, and an international normalized ratio (inr) of 0.8. urinalysis showed severe pyuria and gross hematuria. other laboratory findings included: glucose 100 milligram/deciliter, blood urea nitrogen (bun) 38 mg/dl, serum creatinine 2.6 mg/dl, sodium 135 meq/l, potassium 4.1 meq/l, and serum glutamic oxaloacetic transaminase (sgot) 48 u/l. the patient underwent abdominopelvic computed tomography (ct) scan without contrast material due to renal insufficiency. axial view of abdominopelvic ct scan showed thick-wall bladder with pseudo-diverticula, dilatation of bilateral proximal ureter, and left hydronephrosis (figure 1). coronal view of ct scan showed a contracted heart-shape bladder (figure 1). a diagnosis of ketamine-associated uropathy, complicated with urinary tract infection, was made. the patient was started on intravenous fluids, parenteral antibiotics, and continuous urinary drainage through a foley. on the following days, urine and blood cultures yielded escherichia coli. he recovered with conservative management and was discharged 12 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem cc. wu and acm. lin 2 figure 1: axial (left) and coronal (right) views of the patient’s abdominopelvic computed tomography scan. days later. 3. discussion ketamine is a non-competitive n-methyl-d-aspartate receptor antagonist medication, mainly used for short-acting general anesthesia, chronic pain, sedation, depression, and bipolar disorder (2). ketamine is also used as a recreational drug due to its hallucinogenic and dissociative effects. because of its low price and easy usage, use of ketamine as a recreational drug is being increasingly reported worldwide. long-term ketamine abuse may cause severe lower urinary tract symptoms and voiding dysfunction. chronic ketamine use can damage many organs including the brain, heart, liver, gastrointestinal tract, and genitourinary system (3). urinary tract abnormalities are the most commonly reported undesirable chronic effects related to ketamine abuse (4, 5). chronic ketamine abuse may be associated with ulcerative cystitis, urge incontinence, decreased bladder volume, decreased bladder compliance, detrusor overactivity, and painful hematuria (6). secondary renal damage can occur in long-term abusers (7, 8). lower urinary tract symptoms may be associated with chronic urinary infection and ketamineassociated ulcerative cystitis. cessation of ketamine use and proper treatment may improve most lower urinary tract symptoms. 4. limitations patients with a history of chronic ketamine use with persistent lower tract symptoms need to be encouraged to immediately cease its use and refer to a urologist for assessment. contracted bladder patients with frequent recurrent urinary tract infection should be investigated. ct is useful in detecting the causes of urinary symptoms, such as calculi, bladder debris, bladder fibrosis, and poor bladder compliance, as well as in early diagnosis of ketamine-associated uropathy. 5. declarations 5.1. acknowledgments we acknowledge all the staff of department of diagnostic radiology and emergency department of shin kong wu ho-su memorial hospital, taipei, taiwan. 5.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the internal committee of medical journal editors. 5.3. funding and support none. 5.4. conflict of interest none. references 1. yek j, sundaram p, aydin h, kuo t, ng lg. the clinical presentation and diagnosis of ketamine-associated urinary tract dysfunction in singapore. singapore medical journal. 2015;56(12):660. 2. grady se, marsh ta, tenhouse a, klein k. ketamine for the treatment of major depressive disorder and bipolar dethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e12 pression: a review of the literature. mental health clinician. 2017;7(1):16-23. 3. hong y, yee c, tam y, wong jh, lai p, ng c. management of complications of ketamine abuse: 10 years’ experience in hong kong. hong kong medical journal. 2018;24(2):17581. 4. ng s, tse m, ng h, lau fl. emergency department presentation of ketamine abusers in hong kong: a review of 233 cases. hong kong medical journal. 2010;16(1):6-11. 5. hanna j. kluts: ketamine and lower urinary tract symptoms. erowid extracts. nov 2010;19:12-4. 6. chu psk, ma wk, wong scw, chu rwh, cheng ch, wong s, et al. the destruction of the lower urinary tract by ketamine abuse: a new syndrome? bju international. 2008;102(11):1616-22. 7. wu s, lai y, he y, li x, guan z, cai z. lower urinary tract destruction due to ketamine: a report of 4 cases and review of literature. journal of addiction medicine. 2012;6(1):85-8. 8. mason k, cottrell a, corrigan a, gillatt d, mitchelmore a. ketamine-associated lower urinary tract destruction: a new radiological challenge. clinical radiology. 2010;65(10):795-800. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion limitations declarations references archives of academic emergency medicine. 2021; 9(1): e13 https://doi.org/10.22037/aaem.v9i1.1092 le t t e r to ed i to r mass suicide of covid-19 patient’s survivors; a clinical experience mohammad mahdi forouzanfar1, ziba shahini2, behrouz hashemi1, sahar mirbaha1∗ 1. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of social work, shahid beheshti university of medical sciences, tehran, iran. received: january 2021; accepted: january 2021; published online: 13 january 2021 cite this article as: mm forouzanfar, shahini z, hashemi b, mirbaha s. mass suicide of covid-19 patient’s survivors; a clinical experience. arch acad emerg med. 2021; 9(1): e13. dear editor, we had just started our shift at the emergency department that day, when a highly agitated pale middle-aged woman was brought to the emergency department by the emergency medical service (ems). behind her were 5 of her family members, 3 were her children and the other 2 were her sister and her brother in law. she was immediately transferred to the cardiopulmonary resuscitation (cpr) room and cardiac and respiratory monitoring were provided, central venous access was established (due to lack of peripheral vascular access because of severe hypotension), and fluid infusion was performed. during the time these services were provided, a history was taken from her relatives. the patient’s children were the ones who provided the history: apparently, their father had died 20 days before due to covid-19. dealing with his death was difficult for them, especially for their mother, due to the strong emotional bond with the father. the whole family had decided to commit suicide by consuming rice tablet (aluminum phosphide). on the day we met them, the mother takes an unknown number of aluminum phosphide tablets without the children knowing and then drinks instant coffee on the balcony, after which she develops symptoms and is brought to the emergency department. after a little while, the mother develops cardiorespiratory arrest in cpr, she is intubated and resuscitation is performed and her cardiac rhythm returns for 1 hour, but then develops arrest again and her heart stops beating despite cardiac resuscitation. giving the news of her death and informing the anxious relatives waiting behind the closed doors is done with difficulty, they can be heard crying, moaning and shouting and sometimes cursing the healthcare staff. ∗corresponding author: sahar mirbaha; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel: +989121549505, email: dr.saharmirbaha@gmail.com. during the second cpr, the hospital’s social worker is informed and consultation is received, especially regarding the patient’s children, and subsequently the social emergency gets involved. a few minutes later, the social worker goes to the patient’s family, explains the patient’s condition, and says that there isn’t much hope for her to return and provides consultations regarding psychological support of the family members and dangers threatening the children and emphasizes the need for involvement of the social emergency. a short while after that, the mother’s death is announced. the social worker informs the eldest and calmest family member that each of the children should be supported by a number of family members and should not be alone at home. in addition, social emergency gets involved and sends a group of experts to take necessary measures. from this point on, the information we will report about the patient and her family was provided by the elder daughter of the patient who is 30 years old (master of educational management): in the midst of the tumultuous situation and mourning and consultation with the family members, the 32-year-old son of the patient (electrical engineer), who had been very psychologically disturbed and cursed the healthcare staff after the death of his mother, leaves the emergency department for a phone call. he seemingly calls the seller of the deadly tablet and leaves the emergency department without notice. others had thought that he is mourning somewhere in the courtyard of the hospital. she said that her brother had left the hospital immediately after the phone call when others were receiving consultations in the hospital. after buying the tablet, he goes to his father’s grave, takes the tablet and dies there. the family members called him when they noticed that he is missing and since he did not answer, they called the police. the police found his dead body beside his father’s grave 3 hours later and informed the family. he was transferred to a hospital, which this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem mm. forouzanfar et al. 2 was in vain. the younger sister who is 22 years old (master of genetics), was admitted to a mental hospital and received electroconvulsive therapy (ect) twice during her admission. however, the older sister seems to be mournful but coping with this mental crisis. we would like to emphasize that this family was sufficiently wealthy and highly educated from a socioeconomic point of view. the recent coronavirus epidemic had serious social and mental effects on the people of china, especially those who were quarantined and could not have face to face communications and express traditional social behaviors (1). anxiety, fear and stress always accompany those who are affected and suspected. the families of patients with covid-19 and people whose loved ones are in close contact with infected patients face these mental problems and this can easily turn into mass hysteria. in addition, epidemiologists, scientists, physicians, and all the healthcare professionals who are known as healthcare heroes can also be affected with these psychological problems due to involvement in this global crisis and sacrificing themselves. numerous studies have reported the negative psychological effects of covid-19 including symptoms of stress due to trauma, disorientation and confusion, and anger in those involved in stressful situations. the long duration of quarantine, being afraid of getting sick, disappointment, exhaustion, storing insufficient food, incomplete information, financial problems, and stigma have been identified as stressors in the covid-19 epidemic (2, 3). therefore, for improvement of psychological wellbeing in iran, people should receive psychological services and be informed of ways to access these services through various sources including social media, phone, online services, or in person. groups of people who might need psychological services should be identified and categorized for establishment of the connection. for instance: patients with covid-19 (with mild to severe symptoms), patients whose covid-19 test has become positive, families, friends and colleagues of the patients, all healthcare workers, researchers who study covid-19 in laboratories, people living in regions with high risk of covid-19, those taking care of elderly family members in their house, mothers, especially those who have 8 – 10-year-old children, pregnant women, child laborers and people who do not receive much attention, all people in any profession, patients with special mental diseases (such as obsessive compulsive disorder and mysophobia) and psychological patients who should consume medication (4). it seems that psychological traumas due to covid-19 are more dangerous than the pathogenic nature of the virus. this bitter clinical experience was a tragedy similar to thousands of similar incidents that might only attract the attention of a few or be neglected due to unawareness. the necessity of providing psychological support for survivors of covid-19 patients is not less than using effective drugs for patients with covid-19, both are lifesaving. therefore, providing vigorous psychological support for families of these patients and not abandoning them in the face of a peculiar sorrow caused by an invisible enemy through employing social workers and social emergency teams, and establishing psychological and psychiatric consultation groups are strongly recommended and can reduce future mental disorders and suicides. the physicians are recommended to play a role by identifying these traumas, using the suggested methods, and asking for consultation and social aid for the patients’ survivors and following up on their psychological wellbeing. 1. declarations 1.1. conflicts of interest none. 1.2. funding support none. 1.3. authors’ contributions all authors passed the criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 1.4. ethics the authors adhered to confidentiality of patients’ profiles and ethical recommendations regarding research in biomedical field (ethics code: ir.sbmu.retech.rec.1399.853). references 1. zhang j, wu w, zhao x, zhang w. recommended psychological crisis intervention response to the 2019 novel coronavirus pneumonia outbreak in china: a model of west china hospital. precision clinical medicine. 2020;3(1):3-8. 2. duan l, zhu g. psychological interventions for people affected by the covid-19 epidemic. the lancet psychiatry. 2020;7(4):300-2. 3. yang y, peng f, wang r, guan k, jiang t, xu g, et al. the deadly coronaviruses: the 2003 sars pandemic and the 2020 novel coronavirus epidemic in china. journal of autoimmunity. 2020:102434. 4. shojaei sf, masoumi r. the importance of mental health training for psychologists in covid-19 outbreak. middle east journal of rehabilitation and health studies. 2020;7(2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2022; 10(1): e14 le t t e r to ed i to r intravenous lipid emulsion for treating tramadolinduced seizures: surprising but worth considering for future studies; a letter to editor bruno mégarbane1∗, ahmed s. gouda2 1. department of medical and toxicological critical care, lariboisière hospital; paris, university; inserm umrs-1144, paris, france. 2. national egyptian center for toxicological researches, faculty of medicine, university of cairo, cairo, egypt. received: january 2022; accepted: january 2022; published online: 9 february 2022 cite this article as: mégarbane b, s. gouda a. intravenous lipid emulsion for treating tramadol-induced seizures: surprising but worth considering for future studies; a letter to editor. arch acad emerg med. 2022; 10(1): e14. https://doi.org/10.22037/aaem.v10i1.1541. dear editor; we read with interest the article reporting benefits of intravenous lipid emulsion (ile) in preventing tramadol-induced in-hospital seizures in poisoned patients (1). we would first like to congratulate the authors for this impressive randomized investigation. however, we wish to comment on their findings. the main presumed mechanism of action for ile in acutely poisoned patients, named “lipid sink”, is limiting tissue distribution of lipophilic drugs potentially causing toxicity. based on an in vitro model, ile’s ability to sequester a drug was shown to parallel its octanol-water partition coefficient (2), defined as the ratio of its concentration in a watersaturated octanolic phase to its concentration in an octanolsaturated aqueous phase and usually expressed as “logp”. prediction of drug binding with ile was additionally improved by combining its logp with volume of distribution (vd), together accounting for 88% of ile-attributed variation in its serum concentration decrease (2). with a logp of 1.34 (3), only 1% decrease in serum tramadol level should be expected with ile. by combining its logp and vd of 2.7l/kg (3), predicted lipid extraction efficiency would also remain extremely low (<10%), precluding any important clinical benefit. noteworthy, this issue would have been different in case of much more lipophilic opioids such as fentanyl (logp of 4.05 and vd of 4l/kg), with a predicted ile-related decrease in serum concentration of >40% (2, 3). another issue when considering ile to reverse toxicity af∗corresponding author: bruno mégarbane; hôpital lariboisière, réanimation médicale et toxicologique, 2 rue ambroise paré, 75010 paris, france. e-mail: bruno.megarbane@lrb.aphp.fr, orcid: https ://orcid.org/0000-00022522-2764 . ter oral exposure is the delay between ingestion and hospital admission, which is important since patients are usually referred after the onset of the first toxic symptoms. management commonly starts at a time in the poisoning course when the drug distribution phase is almost complete. however, ile’s ability to redistribute the toxicant from its target organs is much more controversial. although tramadol causes a high risk of seizure, seizure event rate in tramadol-overdosed patients was determined at 38% (95%ci: 2749) versus 37% (95%ci: 12 62) in tramadol abusers and 3% (95%ci: 2 3) in users with therapeutic dosage (4). seizure risk is dose-dependent, more marked in patients with existing seizure disorders or previous seizure history. various co-ingestions such as serotonergic medications may increase the risk, while benzodiazepines, frequently used in addicts, may decrease it. these observations suggest that one in three tramadol-exposed patients admitted to the emergency department is actually at risk of seizing. in kazemifar’s trial, 56% of the included patients seized before receiving one of the two arm treatments and 37% of the controls presented in-hospital seizures (1). in this view, patients included in the study appeared at an unusually elevated risk of seizing, especially given the relatively low mean ingested tramadol dose reported with a huge standard deviation (229 ± 135 mg in the intervention and 195 ± 156 mg in the control group, whereas the pharmacological single dose is 100 mg and the daily dose 400 mg). tramadol typically results in early, single, brief, self-limiting generalized tonic-clonic seizures, often occurring within 46h post-ingestion (5). multiple seizure risk is also low (6). clinical toxicologists even stated the lack of need to administer anticonvulsants for seizure prophylaxis beyond that required for treating ongoing convulsions or other comorbidities in tramadol-poisoned patients who presented an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. mégarbane et al. 2 initial seizure (6). interestingly, a decision tree based on readily available parameters on admission was published in the journal to help clinicians identifying tramadol-poisoned patients at high risk for seizure (area under the roc curve = 0.77; 95%ci: 0.67–0.87) to possibly treat them with prophylactic anticonvulsants (7). current recommendations on ile use were published by an international collaborative workgroup supported by the american and european societies of clinical toxicology (8). when managing life-threatening toxicity, guidelines recommended not using ile as first-line therapy. as part of treatment modalities and if other therapies fail, guidelines recommended using ile only in bupivacaine toxicity, but suggested using ile for toxicity due to other local anesthetics, amitriptyline, and bupropion. recommendations were neutral for all other toxins and variable for the management of non-life-threatening toxicity, relying on the expected risk/benefit balance for each involved toxicant. despite possible biases and surprising results, kazemifar’s findings (1) clearly question whether tramadol-induced seizure prophylaxis should be added to the list of ile indications. alternatively, in tramadol-poisoned patients at risk of seizures or respiratory depression, more specific antidotes, i.e., naloxone, diazepam, or their combination, might also be considered, as suggested in a rat model (9). therefore, to improve tramadol-poisoned patients’ management, further randomized studies with better design and larger cohorts, comparing ile with alternative therapeutic strategies should be considered. 1. declarations 1.1. acknowledgment none. 1.2. authors’ contributions bruno mégarbane wrote the first draft. ahmed s. gouda commented on the draft. both authors agreed with the final version of the manuscript. 1.3. financial disclosure the authors declare no financial interests in relation to the manuscript. 1.4. funding support none declared. references 1. kazemifar am, yazdi z, bedram a, mahmoudi j, ziaee m. effects of intravenous lipid emulsion on tramadolinduced seizure; a randomized clinical trial. arch acad emerg med. 2021;9(1):e20. pubmed pmid: 33870207; pubmed central pmcid: pmcpmc8035696. 2. french d, smollin c, ruan w, wong a, drasner k, wu ah. partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. clin toxicol (phila). 2011;49(9):8019. doi: 10.3109/15563650.2011.617308. pubmed pmid: 21981684. 3. medicine nlo. tramadol [cited 2022 15th jan 2022]. available from: https://pubchem.ncbi.nlm.nih.gov/compound/tramadol. 4. nakhaee s, amirabadizadeh a, brent j, miri-moghaddam e, foadoddini m, farrokhfall k, et al. tramadol and the occurrence of seizures: a systematic review and meta-analysis. crit rev toxicol. 2019;49(8):710-23. doi: 10.1080/10408444.2019.1694861. pubmed pmid: 31914355. 5. jovanovic-cupic v, martinovic z, nesic n. seizures associated with intoxication and abuse of tramadol. clin toxicol (phila). 2006;44(2):143-6. doi: 10.1080/1556365050014418. pubmed pmid: 16615669. 6. shadnia s, brent j, mousavi-fatemi k, hafezi p, soltaninejad k. recurrent seizures in tramadol intoxication: implications for therapy based on 100 patients. basic clin pharmacol toxicol. 2012;111(2):133-6. doi: 10.1111/j.17427843.2012.00874.x. pubmed pmid: 22364547. 7. bazmi e, behnoush b, hashemi nazari s, khodakarim s, behnoush ah, soori h. seizure prediction model in acute tramadol poisoning; a derivation and validation study. arch acad emerg med. 2020;8(1):e59. pubmed pmid: 32613201; pubmed central pmcid: pmcpmc7305636. 8. gosselin s, hoegberg lc, hoffman rs, graudins a, stork cm, thomas sh, et al. evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning(). clin toxicol (phila). 2016;54(10):899923. doi: 10.1080/15563650.2016.1214275. pubmed pmid: 27608281. 9. lagard c, malissin i, indja w, risede p, chevillard l, megarbane b. is naloxone the best antidote to reverse tramadol-induced neuro-respiratory toxicity in overdose? an experimental investigation in the rat. clin toxicol (phila). 2018;56(8):737-43. doi: 10.1080/15563650.2017.1401080. pubmed pmid: 29148295. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2021; 9(1): e16 https://doi.org/10.22037/aaem.v9i1.1014 ca s e re p o rt plastic bronchitis in a five-year-old boy treated using extracorporeal membrane oxygenation; a case report tsuyoshi nojima1, hiromichi naito1∗, takafumi obara1, kohei tsukahara1, atsunori nakao1 1. department of emergency, critical care and disaster medicine, okayama university graduate school of medicine, dentistry and pharmaceutical sciences, okayama, japan. received: december 2020; accepted: december 2020; published online: 27 january 2021 abstract: plastic bronchitis is an uncommon disorder marked by the production of bronchial casts and acute respiratory failure development. in pediatric cases, influenza infection sometimes results in the obstruction of bronchi and leads to this potentially life-threatening condition. we report the case of a five-year-old boy with plastic bronchitis related to influenza a infection, which could only be recovered by the use of extracorporeal membrane oxygenation (ecmo). ecmo could effectively provide sufficient oxygenation for patients suffering from severe reversible acute respiratory failure. if patients infected with the influenza virus present acute respiratory distress with total lung atelectasis, clinicians should consider the diagnosis of plastic bronchitis and the subsequent treatment interventions with ecmo in a severe cases. keywords: bronchitis; influenza a virus; extracorporeal membrane oxygenation; respiratory distress syndrome cite this article as: nojima t, naito h, obara t, tsukahara k, nakao a. plastic bronchitis in a five-year-old boy treated using extracorporeal membrane oxygenation; a case report. arch acad emerg med. 2021; 9(1): e16. 1. introduction plastic bronchitis is a life-threatening complication defined by the production of large, branching bronchial casts that are often expectorated but may be only recognized during bronchoscopy. clinical manifestations may include fast and incremental respiratory distress with lung consolidation or atelectasis showing on chest radiograph. in most patients, bronchial casts are secondary to underlying heart or lung diseases known to be associated with allergy, asthma, or influenza infection (1-4). here, we report the case of a five-year-old boy with plastic bronchitis associated with influenza a successfully treated with extracorporeal membrane oxygenation (ecmo). our case indicates that in pediatric patients suffering from severe plastic bronchitis with acute respiratory failure, venovenous (vv ) ecmo may be the only effective lifesaving procedure for providing sufficient oxygenation. if patients infected with the influenza virus present the combination of total lung atelectasis and acute respiratory distress, clinicians should con∗corresponding author: hiromichi naito; okayama university graduate school of medicine, dentistry and pharmaceutical sciences, department of emergency, critical care, and disaster medicine. 2-5-1 shikata, okayama, japan 700-8558. tel: +81-86-235-7426, fax: +81-86-235-7427, email: naito.hiromichi@gmail.com sider the diagnosis of plastic bronchitis and intervene with early bronchoscopy and consider application of ecmo. 2. cases presentation a five-year-old boy, 15 kilograms in weight and 107 cm in height, was admitted to a local hospital after three days of fever, coughing, and aggravating dyspnea. a rapid influenza test conducted using a nasopharyngeal swab was positive for the influenza a virus. he was transported to our tertiary emergency medical center due to respiratory failure. upon physical examination after emergent transfer to our emergency department, his blood pressure was 174/101 mmhg, pulse rate was 179 bpm, respiratory rate was 30/minute, and body temperature was 37.8°c. his percutaneous oxygen saturation was 86% with a respirator delivering 100% oxygen, and breathing sounds were decreased in both lungs. his venous blood gas analysis and blood chemical analysis results are shown in table1. his chest x-ray and computed tomography showed pneumothorax in both lungs and consolidation in the right lung (figure 1). due to deoxygenation and deterioration as a result of respiratory distress, the patient had to be intubated and placed under mechanical ventilation. flexible bronchoscopy revealed thick secretions and right lower lobe bronchus lumen obstruction with a rubbery, whitish substance consistent with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. nojima et al. 2 table 1: blood chemical analysis on arrival variable value variable value venous blood gas clinical chemistry test ph 7.201 crp (mg/dl) 10.21 paco2 (mmhg) 73.7 tp (g/dl) 6.4 hco3 (mmol/l) 27.4 alb (g/dl) 3.7 be (mmol/l) -8.1 ast (iu/l) 28 ag (mmol/l) 18.7 alt (iu/l) 15 lactate (mmol/l) 0.8 ldh (iu/l) 428 complete blood count alp (iu/l) 700 wbc (/µl) 34,010 g-gtp (iu/l) 10 neut (%) 94 ck (iu/l) 56 lymp (%) 3 t-bil (mg/dl) 0.7 mono (%) 2.5 s-amy (iu/l) 26 hb (g/dl) 13.1 bun (mg/dl) 16.7 plt (/µl) 40.5×104 crea (mg/dl) 0.28 blood coagulation test ua (mg/dl) 4.9 inr 1.22 na ( meq/l) 146 aptt (sec) 29.2 k ( meq/l) 4.6 fibrinogen (mg/dl) 454 cl ( meq/l) 106 fdp (µg/ml) 34 ca ( mg/dl) 9.4 d-dimer (µg/ml) 18.1 figure 1: the chest x-ray and computed tomography on arrival showed pneumothorax and pleural effusion in both lungs. an endobronchial cast (figure 2). the clinical diagnosis of acute respiratory failure, pneumothorax, and plastic bronchitis associated with influenza a infection was made. considering persistent respiratory distress in 41 of peak inspiratory pressure and subsequent circulatory collapse, the patient was placed on venous-arterial (va) ecmo through the right cervical artery and vein with chest drainage tubes on both chest cavities. initial va-ecmo conditions were as follows: oxygenator; biocube (nipro, japan), venous line; right internal jugular vein using biomedicust m nextgen catheter 17fr (medtronic, mexico), arterial line; right internal jugular artery using biomedicus cateter 12fr (medtronic, mexico), blood flow 1.5l/min, speed 2,780 rpm, oxygen sweep gas 3.0l/min, and the fraction of oxygen 0.8 using heparin. antimicrobial treatment included 2,250 mg/day of cefotaxime, 900 mg/day of vancomycin, and 150 mg/day of peramivir. figure 3 shows the progress after hospitalization. on the fourth day, since initiation of va-ecmo had stabilized the patient’s circulatory condition, va-ecmo was converted to vv-ecmo through the right cervical vein and femoral vein. initial vv-ecmo conditions were as follows: oxygenator; biocube (nipro, japan), venous line; right internal jugular vein using biomedicust m nextgen catheter 17fr (medtronic, mexico), arterial line; right femoral vein usthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e16 figure 2: photograph of a representative cast spontaneously expectorated from a patient with plastic bronchitis during bronchoscopy. figure 3: progress of respiratory parameters of the patient during hospitalization. pip: peak inspiratory pressure, va-ecmo: venousarterial extracorporeal membrane oxygenation, vv-ecmo: venovenous extracorporeal membrane oxygenation, p/f: pao2 /fio2 . ing biomedicust m nextgen cateter 15fr (medtronic, mexico), blood-flow 1.52 l/min, speed 2010 rpm, oxygen sweep gas 2.0 l/min, and the fraction of oxygen 1.0 using heparin. on the eighth day, his breathing improved, so we switched from vv-ecmo to ventilation management only. mechanical ventilator conditions were as follows: assist mode and control mode by pressure control ventilation; positive endexpiratory pressure 5 cmh2o; the fraction of oxygen 0.6; pressure control 15 cmh2o; and respiratory rate 15. frequent removal of purulent mucous plugging of the airway was required. ecmo support was discontinued after nine days. the patient was gradually weaned off respiratory support, extubated on day 20, and transferred to a rehabilitation hospital on day 21. he has remained well over a 2-month follow-up period. 3. discussion plastic bronchitis is an uncommon and underrecognized but life-threatening condition marked by notable blockage of the large airways by mucous plugs (5). prompt diagnosis and early intervention, including removing the firm, cohesive, branching casts using bronchoscopy, are critical. mechanical ventilation is not always successful in critically ill plastic bronchitis patients. high airway pressure to achieve adequate oxygenation may result in barotrauma, as seen in our patient. the fast clinical deterioration that does not respond to standard therapies makes ecmo a critical adjunct therapy for plastic bronchitis treatment. the rubbery casts in the airway seen in plastic bronchitis are known to comprise fibrin, mucin, or a mixture of both and can obstruct the airways completely or partially. according to a recent well-defined classification of casts based on their composition and underlying pathology (6), casts are divided into two types: inflammatory casts comprising fibrin and dense inflammatory infiltrate associated with respiratory infection or asthma (type 1), and acellular casts comprising mostly mucin related to congenital heart diseases (type 2). histological examination of the casts can point to underlying diseases and may be helpful in therapeutic decision making. although acute mortality can occur in patients with both types of casts, standard therapeutic strategies have not been established. type 1 cast survivors seem to be well-controlled with inhaled steroids. optimal therapy for type 2 cast patients has not been fully determined; prognosis probably depends on underlying cardiac status. various treatment options have been advocated (7). in addition to repeated bronchoscopic extraction of casts, clinicians should consider inhalation heparin when treating the underlying disorders fail, and the casts are largely composed of fibrin (1, 8, 9). heparin is ineffective for fibrin-containing casts but has anti-inflammatory properties that can reduce the secretion of mucin. chest physiotherapy, acetylcysteine, dnase, and systemic corticosteroids have all been used (10). since tissue factor activation of the fibrin pathway can attenuate vascular leak, case reports have shown that inhalation of recombinant tissue plasminogen activator can improve plastic bronchitis through fibrin depolymerization (8). of note, asthma medication administration, like inhaled corticosteroids or beta-agonists, provides only a marginal benefit in most plastic bronchitis cases. 4. conclusion in pediatric patients with fast and progressive respiratory distress and lung consolidation or atelectasis showing on chest radiograph associated with influenza infection, clinicians should consider the possibility of plastic bronchitis and should intervene with early bronchoscopy treatment. for patients with life-threatening progressive respiratory failure, in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. nojima et al. 4 whom significant cast obstruction may advance to cardiorespiratory collapse, prompt therapy with ecmo may be effective and lifesaving, andit may facilitate full recovery of normal pulmonary function. 5. ethical issues written informed consent was obtained from the patient for publication of this case report and accompanying images. this case report was approved by the ethics committee of okayama university (ethics code: k2103-032 ). 6. declarations 6.1. acknowledgements no funding supported this study. 6.2. authors’ relationships all authors met the criteria for authorship contribution based on the international committee of medical journal editors’ recommendations. 6.3. conflict of interest the authors declare no conflicts of interest. 6.4. funding none. references 1. deng j, zheng y, li c, ma z, wang h, rubin bk. plastic bronchitis in three children associated with 2009 influenza a(h1n1) virus infection. chest. 2010;138(6):1486-8. 2. zhang x, vinturache a, ding g. plastic bronchitis in a 3year-old boy. cmaj. 2019;191(48):e1336. 3. okada y, okada a, narumiya h, iiduka r, katsura k. bloody bronchial cast formation due to alveolar hemorrhage associated with h1n1 influenza infection. intern med. 2017;56(20):2747-51. 4. kim s, cho hj, han dk, choi yd, yang es, cho yk, et al. recurrent plastic bronchitis in a child with 2009 influenza a (h1n1) and influenza b virus infection. j korean med sci. 2012;27(9):1114-9. 5. brogan tv, finn ls, pyskaty dj, jr., redding gj, ricker d, inglis a, et al. plastic bronchitis in children: a case series and review of the medical literature. pediatr pulmonol. 2002;34(6):482-7. 6. seear m, hui h, magee f, bohn d, cutz e. bronchial casts in children: a proposed classification based on nine cases and a review of the literature. am j respir crit care med. 1997;155(1):364-70. 7. rubin bk. plastic bronchitis. clin chest med. 2016;37(3):405-8. 8. heath l, ling s, racz j, mane g, schmidt l, myers jl, et al. prospective, longitudinal study of plastic bronchitis cast pathology and responsiveness to tissue plasminogen activator. pediatr cardiol. 2011;32(8):1182-9. 9. soyer t, yalcin s, emiralioglu n, yilmaz ea, soyer o, orhan d, et al. use of serial rigid bronchoscopy in the treatment of plastic bronchitis in children. j pediatr surg. 2016;51(10):1640-3. 10. madsen p, shah sa, rubin bk. plastic bronchitis: new insights and a classification scheme. paediatr respir rev. 2005;6(4):292-300. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction cases presentation discussion conclusion ethical issues declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 158 emergency (2014); 2 (4): 158-161 original research inter-rater agreement of emergency nurses and physicians in emergency severity index (esi) triage mehrdad esmailian, majid zamani*, fatemeh azadi, faezeh ghasemi department of emergency medicine, isfahan university of medical sciences, isfahan, iran abstract introduction: triage is one of the most important systems in patients prioritizing at the time of arrival to hospital. based on the severity of the injury and the need for treatment, this system manages patients in the least time, which could lead to rotation of patients with high reliability and safety. currently, the most accepted method for triage is emergency severity index (esi) system, considered as five-level triage method, too. this method were implemented in al zahra hospital of isfahan by trained nurses since march to may 2010. this study was aimed to evaluate the accuracy of emergency nursing triage using esi. methods: this prospective cross sectional study was carried out on 601 patients referred to al-zahra hospital of isfahan through may 2010. the patients’ triage level were determined by physicians and nurses separately and the results compared. to define the level of agreement between two groups (inter-rater agreement), the kappa index was evaluated. to specify the association between the time interval of initial triage and patient final status, chi-square test was applied using spss 18 statistical software. results: there was no significant difference between results of nurses and physicians triage (p<0/0001). the agreement level (kappa index) between two groups was 94% (95% ci: 0.931-0.957). of 601 patients, 44.1% ones were hospitalized at the emergency department, 52.6% discharged and 3.3% died. the average of time interval between nursing triage and physician visit was 9.55 minutes at the level one triage, 21.64 minutes at level two, 26.03 minutes at level three, 26.93 minutes at level four, and 11.70 minutes at level five. conclusion: it seems that there is an acceptable inter-rater agreement between emergency nurses and physicians regarding patients’ triage in terms of esi system. key words: triage; nurses; physician-nurse relations; emergency medicine cite this article as: esmailian m, zamani m, azadi f, ghasemi f. inter-rater agreement of emergency nurses and physicians in emergency severity index (esi) triage. emergency. 2014;2(4):158-61. introduction:1 he rate of emergency department (ed) visits is increasing and need for accurate and reliable tools is inevitable for classification of patients based on severity of emergency (1-5). various methods have been designed for this purpose such as traffic director, manchester system, canadian system, spot – check, and comprehensive triage (6-11). through these methods, a five-level severity index or emergency severity index (esi) recognized as a valid and accurate system which is not only prioritize patients, but also follow their treatment process for better access to medical facilities and services (12, 13). in comparison with the three-level triage, this system has higher validity and reliability, and successfulness in use of financial, human and time resources (14, 15). esi first was designed in united states of america in 1990 and now has *corresponding author: majid zamani; al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989131585086; fax: +983116685555. email: mzamani93@yahoo.com received: 13 may 2014; accepted: 5 june 2014 been recognized as the gold standard of triage in many countries, such as australia, canada, and united kingdom (1, 12, 16-20). because of simplicity, ease of learning, operational and conceptual approach, this triage method seems to be the most appropriate system for our country (iran), too. since the knowledge and experience of nurses are very important in accurate triage, several studies examined the role of their knowledge and awareness in prioritizing of patients (2, 21). esi triage system was implemented by trained nurses through may 2010 in alzahra hospital of isfahan. in the present study, the accuracy of esi triage by emergency nurses was evaluated. methods: six hundred and one patients referred to the ed of alzahra hospital, isfahan, iran, were triaged based on esi version four recommendation by physicians and trained nurses during march to april 2008. they triaged patients separately while were unaware to the results of each other. the study protocol was approved by the ethics committee of medical university of isfat mailto:mzamani93@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 159 esmailian et al emergency (2014); 2 (3): ***-*** han. a checklist was fulfilled for each patients, contained demographic data (age, sex, date, and cause of admission), nurses and physicians triage results, time interval between the initial triage and first visit by physicians, the outcome of the patient, and the time of discharge from the ed. hospitalization, discharging from ed and mortality was considered as the outcomes. the sample size was calculated considering to p=0.50, d=0.1, and α=0.05 (n=96). all data were analyzed with chi-square and pearson correlation tests using spss version 18 statistical software. p<0.05 was considered as significant. the weighted kappa index (κ) was used for assessment of inter-rater reliability between the triage of nurse and physician (17).the weighted kappa with 95% confidence interval was reported. kappa index less than 0.2, 0.2-0.4, 0.6-0.8 and more than 0.8 were considered as week, moderate, good, and excellent, respectively (22, 23). results: there was no significant difference between nurses and physicians triage. total calculated weighted kappa was 94% (95% ci: 0.931-0.957; p<0.0001). table 1 shows the percentage of agreement between two groups in different levels of triage. of 601 patients, 316 (52.6%) were discharged from ed, 265 (44.1%) hospitalized, and 20 (3.3%) died (table 2). the time interval between triage and first physician visit was 0.0 minutes in level one, 12.64±5.0 in level two, 26.03± 9.6 in level three, 62.93±17.3 in level four, and 110.70 ±26.8 in level five (table 3 ). discussion: our finding revealed that nurses and physicians triage had more than 90% overlap at all levels of triage indicated the high accuracy of nursing triage. several studies had been shown the accuracy of nurse triage decision. for example, goransson et al demonstrated that registered nurses triage had only 58% agreement with the expected acuity rating. but in this study the wide range (22–89%) of accurate triage clearly was a big limitation (24). abbasi et al., reported low reliability of nursing triage (21). in other hand, the result was in line with gorason et al., declared the high accuracy of nursing triage (25). the total agreement level of this study was acceptable based on recommendation of australian college of emergency medicine, determined the kappa of 0.60 as the minimum acceptatable 1: the number (%) of agreements between two groups in different levels of emergency severity index (esi) triage  total 5 4 3 2 1 esi level 11 0 0 0 0 11 (100) 1 141 0 0 3 138 (95) 0 2 415 0 5 404 (98) 6 0 3 24 0 22 (81) 2 0 0 4 10 10 (100) 0 0 0 0 5 601 10 27 409 144 11 total esi: emergency severity index table 2: final outcomes of patients with different levels of triage after 24 hours  triage levels outcome of patients (%) hospitalized discharged from ed died 1 3 (27.3) 2 (18.2) 6 (54.5) 2 80 (55.6) 54 (37.5) 10 (6.9) 3 175 (42.8) 232 (56.7) 2 (0.5) 4 5 (18.5) 20 (74.1) 2 (7.4) 5 2 (20) 8 (80) 0 (0) total 265 (44.1) 316 (52.6) 20 (3.3) ed: emergency department table 3: the average time interval between initial nursing triage and physician examination (minute)  esi level n* (%) intervals standard** 1 (resuscitation) 11 (100) 0 0 2 (emergent) 138 (95) 12.64±5.0 10-15 3 (urgent) 404 (98) 26.03± 9.6 30-60 4 (nonurgent) 22 (81) 62.93±17.3 60-120 5 (referred) 10 (100) 110.70 ±26.8 120-240 *numbers of agreements between two groups, ** maximum time to point of care (based on manchester triage system) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (4): 158-161 160 ble agreement level (2). similar to our investigation gorason et al. and worster et al. achieved the moderate (0.46) and good (0.76) agreements, respectively (26, 27). based on previous works there were not any significant relation among accuracy of nursing triage and personal characteristics, attitude, and experience level (24, 28). however, nurses’ knowledge has direct relation with appropriate triage of patients (29). it mandates the improvement of staffs’ knowledge regarding the level of patients’ emergency severity; it could be led to minimize the waiting time, enhance the quality of services, and reduce mortalities (30). training is a key factor in change and improvement of nurses’ knowledge. in this regards, several new training techniques can be used to teach the triage such as gaming technology, web-based training, and etc. (31) which improve the accuracy of the triage process. the prolonged time interval between initial nursing triage and physician examination lead to harmful delays in achieving timely emergency care (32). in contrast, shortening the duration of time between patient presentation and treatment, may increase levels of patient satisfaction and reduced ed overcrowding (33). it could be concluded that trained nurses are able to perform appropriate triage of ed patients and improve the patients’ safety and satisfaction, consequently. conclusion: it seems that there is an acceptable inter-rater agreement between emergency nurses and physicians regarding patients’ triage in terms of esi system. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of alzahra hospital of isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on 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prospective multicenter evaluation. ann emerg med. 2012;60(1):71-7.e3. 12. christ m, grossmann f, winter d, bingisser r, platz e. modern triage in the emergency department. dtsch arztebl int. 2010;107(50):892-8. 13. manos d, petrie da, beveridge rc, walter s, ducharme j. inter-observer agreement using the canadian emergency department triage and acuity scale. cjem. 2002;4(1):16-22. 14. eitel dr, travers da, rosenau am, gilboy n, wuerz rc. the emergency severity index triage algorithm version 2 is reliable and valid. acad emerg med. 2003;10(10):1070-80. 15. lohr kn, schroeder sa. a strategy for quality assurance in medicare. n engl j med. 1990;322(10):707-12. 16. shelton r. the emergency severity index 5-level triage system. dimens crit care nurs. 2009;28(1):9-12. 17. richardson jr, braitberg g, yeoh mj. multidisciplinary assessment at triage: a new way forward. emerg med australas. 2004;16(1):41-6. 18. storm-versloot mn, ubbink dt, chin a choi v, luitse js. observer agreement of the 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model in female secondary school students of paveh in 2011. edu res med sci j. 2014;2(3):2-9. 32. göransson ke, ehrenberg a, ehnfors m. triage in emergency departments: national survey. j clin nurs. 2005;14(9):1067-74. 33. finamore sr, turris sa. shortening the wait: a strategy to reduce waiting times in the emergency department. j emerg nurs. 2009;35(6):509-14. archives of academic emergency medicine. 2022; 10(1): e3 rev i ew art i c l e incidence of pediatric perforated appendicitis during the covid-19 pandemic; a systematic review and metaanalysis gholamreza motazedian1, poorya aryanpoor2, ehsan rahmanian3, samaneh abiri3, navid kalani3, naser hatami2, farhad bagherian4, mohammad etezadpour5, roohie farzaneh6, fatemeh maleki7, mahdi foroughian6, mojtaba ghaedi8∗ 1. plastic & reconstructive surgery department, shiraz university of medical sciences, shiraz, iran. 2. student research committee, jahrom university of medical sciences, jahrom, iran. 3. research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. 4. department of emergency medicine, babol university of medical sciences, babol, iran. 5. surgery department, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 6. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 7. department of emergency medicine, faculty of medicine, birjand university of medical sciences, birjand, iran. 8. plastic surgery department, jahrom university of medical sciences, jahrom, iran. received: november 2020; accepted: november 2021; published online: 1 january 2021 abstract: introduction: covid-19 has affected the pattern of referral to medical centers and quarantine against covid19 might delay referral and management of surgical emergencies. this study aimed to compare the pooled event rate of pediatric perforated appendicitis before and during the covid-19 pandemic. methods: this was a systematic review and meta-analysis study based on the prisma guidelines. scopus, web of sciences, and pubmed databases were searched for studies reporting the rate of perforated appendicitis based on the postappendectomy observations or imaging methods. the egger bias test and funnel plot were used to detect and depict publication bias. statistical analysis was performed in comprehensive meta-analysis package version 3. results: twelve studies were eligible for inclusion in our study. the pooled prevalence of pediatric perforated appendicitis in the pre-covid era was 28.5% (ci95%: 28.3 to 28.7%) with a heterogeneity of 99%. in the covid era, the event rate proportion was 39.4% (ci95%: 36.6 to 42.3%) with a heterogeneity of 99%. there was a significant difference in the subgroup analysis within the pre-covid and covid era (p<0.001), showing a higher perforation rate in the covid era. conclusion: our study showed that during the covid-19 pandemic, the rate of perforated appendicitis has significantly increased in comparison to before the covid-19 pandemic. keywords: covid-19; appendicitis, ruptured; abdomen, acute cite this article as: motazedian g, aryanpoor p, rahmanian e, abiri s, kalani n, hatami n, bagherian f, etezadpour m, farzaneh r, maleki f, foroughian m, ghaedi m. incidence of pediatric perforated appendicitis during the covid-19 pandemic; a systematic review and metaanalysis. arch acad emerg med. 2022; 10(1): e3. https://doi.org/10.22037/aaem.v10i1.1421. ∗corresponding author: mojtaba ghaedi; plastic surgery department, jahrom university of medical sciences, jahrom, iran. tel: 009809173222049, email: ghamojtaba247@gmail.com, orcid: http://orcid.org/0000-0002-07615898. 1. introduction diagnosis and decision-making about some diseases like abdominal pain can be challenging for physicians (1). in surgery, the most common cause of abdominal surgery is acute appendicitis. appendicitis is a surgical emergency and a common disease that can present with a variety of symptoms (2). the manifestations of this disease overlap with several other medical conditions. sometimes the complexities this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. motazedian et al. 2 and differences in the way it occurs can lead even the most experienced physicians to mistake it for other conditions (3). in some cases, especially in children, the symptoms may be deceptive and difficult to diagnose, and on the other hand, prolongation of the disease may be life-threatening or cause severe complications (4). therefore, correct and timely diagnosis of the disease requires experience and special skills. lack of ability of children to give an accurate history, delayed diagnosis by parents and physicians, and the presence of nonspecific gastrointestinal disorders are other causes of late diagnosis of acute appendicitis in children (5, 6). appendicitis in pediatric cases is more likely to rupture, and due to the lack of omentum growth in children, peritonitis is more likely to occur and complications are more common (7). in children under 5 years of age, both the diagnosis of acute appendicitis and the risk of appendix rupture is higher (8). currently, since covid-19 has emerged as a pandemic all around the world, some concerns have been raised about the management of surgical emergencies in pediatric cases. covid-19 has a variety of clinical manifestations, including abdominal pain, which can make it difficult for physicians to differentiate acute appendicitis, and as a result, the risk of perforation of the appendix increases (9). additionally, the quarantine imposed during the covid-19 epidemic, as well as the refusal of parents and children to visit hospitals out of fear of getting infected with the virus, could have resulted in the increased rate of perforated appendicitis or its complications. this study aimed to compare the pooled event rate of pediatric perforated appendicitis before and during the covid-19 pandemic. 2. methods 2.1. study design and setting this systematic review and meta-analysis study was done based on the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. we quarried scopus, web of sciences, and pubmed databases for studies irrespective of the study time, limiting results to english articles, cross-sectional and retrospective or prospective studies using the keywords of appendicitis, acute appendicitis, perforated, perforation, appendix, appendectomy, children, and pediatric. the following search strategy was used “(covid-19[mesh major topic]) and (acute abdomen [mesh major topic]) and (appendicitis [title])) or (acute appendicitis [title])) or (appendectomy [title])) or (perforated [title])) or (perforation [title]) and (all child [filter])” in pubmed. scopus search strategy was “#1 title-abs-key (appendicitis or acute appendicitis or appendectomy or perforation) #2 title-abs-key (covid-19 or sars-cov2 or coronavirus) #3 pediatric or children #4 #1 and #2 and #3” and the same with ts function in web of sciences. studies reporting the rate of perforated appendicitis based on the post-appendectomy observations or imaging methods were considered eligible to be included in our study if reporting them in the pediatric age group (under 18 years old). 2.2. quality assessment the newcastle-ottawa quality assessment scale (nos), which was adapted to measure characteristics of quality relevant to population-based studies of incidence, was used to assess the studies’ quality (10). studies having a low possibility of bias were included. 2.3. measured outcome our study outcome was comparing the proportion of perforated appendicitis within two time periods of the post covid-19 era (from december 2019) and pre covid-19 era (before december 2019). studies were included from 1995 to 2021. 2.4. statistical analysis the cochran q test (two-test for heterogeneity) was used to assess the heterogeneity of the studies. i2 and its 95% confidence interval (ci) were used to calculate the percentage of total heterogeneity to total variability. a q test with a p<0.1 or an i2 greater than 60% was considered to show significant statistical heterogeneity. random-effects models with double arcsine transformations were used. a 2-sided p<05 was considered statistically significant, regardless of the i2 statistic. in order to assess the significant difference in proportions between groups in each analysis, we calculated the inter-group p-value; when there was a significant difference, we ran pairwise comparisons and adjusted the level when necessary. a funnel plot was used to depict publication bias. the egger bias test and the begg-mazumdar rank correlation kendall 2 statistic were used to detect asymmetry. statistical analysis was performed in comprehensive meta-analysis package version 3 and bias possibility was visualized using review manager version 5.4.1. 3. results as shown in figure 1, there were 6234 articles found in the initial search, conducted by two independent researchers, from which 1745 duplicated articles were removed. then based on the abstracts, unrelated articles, including review articles, interventional and case-control studies, and studies only on the adult population were excluded from the study. also, articles whose abstract or main text was not available were excluded. finally, 278 potentially related articles were listed for full text review. twelve studies were eligible to be included in our study. a checklist including the name of the researcher, article title, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e3 year and place of study, sample size, and prevalence of perforated appendicitis was used to collect data (table 1). 8 studies were conducted in covid era, also containing datasets of before covid. 9 studies were performed in us, one in pakistan, one in germany, and one in uk. the largest sample size belonged to cheong lh et al. study with 120117 participants. 3.1. prevalence of pediatric perforated appendicitis the pooled prevalence of pediatric perforated appendicitis in the pre-covid era was 28.5% (ci95%: 28.3 to 28.7%) with heterogeneity of 99%. in the covid era event rate proportion was 39.4% (ci95%: 36.6 to 42.3%) with heterogeneity of 99% (p < 0.001; figure 2). egger’s regression revealed no possibility of publication bias (p-2tailed = 0.458), which was in line with the result of begg and mazumdar rank correlation (kendall’s rau=-0.263, p=0.104; figure 3a). the risk of bias in studies and quality of studies, assessed using a modified nos, are presented in figure 3b. most studies showed a low risk of bias. 4. discussion our study showed that there has been an increase in the rate of perforated appendicitis during the covid-19 pandemic in comparison to before the covid-19 pandemic. difficulty diagnosing the disease usually delays the start of treatment and in many cases leads to perforation. while delayed referral to a medical center could also be a potential factor leading to perforation; covid-19 pandemic has decreased public referral to hospitals due to fear of infection (22). due to the high mortality rate, appendicitis is on the list of important diseases in children. considering the rapid progression of this disease in children, the need for timely diagnosis of the disease in order to prevent side effects is emphasized by all surgeons. despite the existence of radiological techniques for diagnosing appendicitis, it is still difficult to diagnose acute appendicitis. additionally, physicians should also be aware of covid-19’s gastrointestinal symptoms that might mimic acute abdomen symptoms (23, 24). in case of ruptured appendicitis, the risk of complications increases. imposing unnecessary surgery can also cause complications such as intestinal adhesions (25). our study indicated that during the covid-19 pandemic, the rate of perforated appendicitis has significantly increased in comparison to before the covid-19 pandemic. additionally, other studies have shown that even before the pandemic, there were seasonal variations in acute appendicitis cases (26) and racial factors might also be affecting the disease prevalence (8). research has shown that even in one country, the prevalence of acute appendicitis might change over the years (27). following the outbreak of covid-19 and the responsibility of hospitals to provide services to patients with covid-19, the provision of medical services to other patients was largely shut down and only emergencies continued; that might have led to missed cases of some urgent diseases including acute abdomen. these patients will suffer if left untreated. therefore, hospitals must be prepared to accept non-covid-19 patients. based on ojetti et al. study, this issue is not limited to appendicitis. the sharp drop in ed visits during the pandemic might be attributed to fear of the virus, implying that individuals with significant conditions did not seek medical help. worrying statistics emerged, in particular, about a decrease in cardiology and neurology admissions. those patients put off seeking medical help out of fear of being exposed to covid-19, resulting in increased morbidity and mortality (28). we recommend global community training for dealing with emergencies during the pandemic so that time-critical medical situations are not neglected. 5. limitations there are many factors affecting the prevalence of perforated appendicitis, such as ethnicity, seasonal variation, and the medical centers’ approaches to acute abdomen, which were not considered in our study. 6. conclusion our study showed that the covid-19 pandemic might have led to an increase in the rate of perforated appendicitis in comparison to the before covid-19 pandemic. one of the serious health concerns during the pandemic is the state of people’s health due to urgent non-covid-19 diseases, which covers a wide range of patients including acute abdomen cases. 7. declarations 7.1. acknowledgments we would like to thank the clinical research development unit of peymanieh educational and research and therapeutic center of jahrom university of medical sciences for providing facilities for this work. 7.2. conflict of interest the authors have declared that no competing interests exist. 7.3. funding/support this research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. motazedian et al. 4 7.4. authors’ contribution gm, mg, nk, mf, and fb conceptualized the study 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coronavirus disease 2019 (covid-19) pandemic: collateral damage is variable. pediatric radiology. 2021;51(11):1991-9. 16. esparaz jr, chen mk, beierle ea, anderson sa, martin ca, mortellaro ve, et al. perforated appendicitis during a pandemic: the downstream effect of covid-19 in children. journal of surgical research. 2021;268:263-6. 17. ali s, khan m, rehman i, uzair m. impact of covid 19 pandemic on presentation, treatment and outcome of paediatric surgical emergencies in a tertiary care hospital. j ayub med coll abbottabad. 2020;32(suppl 1):621-4. 18. place r, lee j, howell j. rate of pediatric appendiceal perforation at a children’s hospital during the covid-19 pandemic compared with the previous year. jama network open. 2020;3(12):e2027948-e. 19. aarabi s, sidhwa f, riehle kj, chen q, mooney dp. pediatric appendicitis in new england: epidemiology and outcomes. journal of pediatric surgery. 2011;46(6):110614. 20. deng y, chang dc, zhang y, webb j, gabre-kidan a, abdullah f. seasonal and day of the week variations of perforated appendicitis in us children. pediatric surgery international. 2010;26(7):691-6. 21. cheong lha, emil s. outcomes of pediatric appendicitis: an international comparison of the united states and canada. jama surgery. 2014;149(1):50-5. 22. mantica g, riccardi n, terrone c, gratarola a. noncovid-19 visits to emergency departments during the pandemic: the impact of fear. public health. 2020;183:40. 23. periyakaruppan m, kumar s, kandasamy s, sangaralingam t, srinivasan s, thiagarajan a, et al. covid abdomen: sars-cov-2 infection presenting as ‘acute abdomen’in a child. the indian journal of pediatrics. 2021;88(3):299-300. 24. saeed u, sellevoll h, young v, sandbaek g, glomsaker t, mala t. covid-19 may present with acute abdominal pain. the british journal of surgery. 2020;107(7):e186. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e3 25. aprahamian cj, barnhart dc, bledsoe se, vaid y, harmon cm. failure in the nonoperative management of pediatric ruptured appendicitis: predictors and consequences. journal of pediatric surgery. 2007;42(6):934-8. 26. ilves i, fagerström a, herzig k-h, juvonen p, miettinen p, paajanen h. seasonal variations of acute appendicitis and nonspecific abdominal pain in finland. world journal of gastroenterology: wjg. 2014;20(14):4037. 27. ilves i, paajanen he, herzig k-h, fagerström a, miettinen pj. changing incidence of acute appendicitis and nonspecific abdominal pain between 1987 and 2007 in finland. world journal of surgery. 2011;35(4):731-8. 28. ojetti v, covino m, brigida m, petruzziello c, saviano a, migneco a, et al. non-covid diseases during the pandemic: where have all other emergencies gone? medicina. 2020;56(10):512. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. motazedian et al. 6 table 1: characteristics of included studies authors n perforated date study interval time country schäfer fm et al. (11) 338 70 2021 march 2018 to may 2019 germany (bavaria) fisher jc et al.(12) 1291 351 2021 jan 2014 to june 2019 us gerall cd et al. (13) 41 4 2021 march to may 2019 us / new york city theodorou cm et al. (14) 592 239 2021 pre-covid era us /california horst kk et al. (15) 59 6 2021 march 1 to may 31 2019 us /rochester, minnesota esparaz jr et al. (16) 102 26 2021 march to may 2019 us /alabama ali s et al. (17) 112 8 2020 march to may 2019 pakistan/peshawar place r et al. (18) 70 13 2020 march 16 to june 7 2019 us/ northern virginia aarabi s et al. (19) 19019 5282 2011 2000 to 2006 new england deng y et al. (20) 31457 10524 2010 1997 us guagliardo mf et al. (8) 9069 2986 2003 1995 and 1997? us / new york and california cheong lh et al. (21) 120117 32321 2014 2004 to 2010 us and canada schäfer fm et al. (11) b 176 49 2021 2020 germany (bavaria) fisher jc et al. (12)b 55 25 2021 jan and may 2020 us gerall cd et al. (13)b 48 7 2021 march to may 2020 us / new york city theodorou cm et al. (14) b 606 255 2021 2019 vs 2020 us /california horst kk et al. (15)b 51 14 2021 march 1 to may 31 2020 us / rochester, minnesota esparaz jr et al. (16)b 103 47 2021 march to may 2020 us /alabama ali s et al. (17)b 42 23 2021 march to may 2020 pakistan/peshawar place r et al. (18) b 90 35 2021 march 16 to june 7 2020 us/ northern virginia n: number. b, same study containing cohorts of both pre-covid and post-covid eras. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e3 figure 1: prisma flow chart of the present study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. motazedian et al. 8 figure 2: forest plot of pooled prevalence of perforated appendicitis in pre-covid and post-covid eras (p < 0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e3 figure 3: funnel plot of the study and risk of bias. (a) funnel plot of the study; (b) risk of bias in the included studies based on the modified newcastle-ottawa quality assessment scale (nos). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e47 or i g i n a l re s e a rc h point-of-care ultrasonography for diagnosis of medial collateral ligament tears in acute knee trauma; a diagnostic accuracy study omid ahmadi1, farhad heydari1∗, keihan golshani1, sirous derakhshan1 1. department of emergency medicine, faculty of medicine, isfahan university of medical sciences, isfahan, iran. received: march 2022; accepted: may 2022; published online: 9 june 2022 abstract: introduction: the use of point-of-care ultrasonography (pocus) for identifying medial collateral ligament (mcl) tears has increased in recent years. this study aimed to evaluate the diagnostic accuracy of pocus in the diagnosis of acute mcl tears of the knee. methods: this prospective cross-sectional study was performed on patients with suspected mcl tear of the knee in the emergency department (ed). after history taking and primary physical examination, radiographic imaging of the knee was done. if there was no fracture in the knee x-ray, the pocus examination was done. all of the patients were asked to refer to an orthopedic clinic, 7-10 days after discharge from ed, for magnetic resonance imaging (mri) evaluation. the second pocus was done in the orthopedic clinic. finally, the findings of pocus and mri were compared in diagnosing mcl injury. results: two hundred and fifty patients with a mean age of 25.05 ± 9.12 years were analyzed (86.8% male). according to the mri findings, as the gold standard, 55(22.0%) patients had mcl injury. the sensitivity, specificity, positive and negative predictive values (ppv and npv ), and accuracy of ultrasound in detection of mcl injury, in comparison with mri were 83.64 (95% ci, 71.20 to 92.23), 94.36% (95% ci, 90.13 to 97.15), 80.70% (95% ci, 69.95 to 88.25), 95.34% (95% ci, 91.83 to 97.38), and 92.00% (95% ci, 87.92 to 95.05), respectively. the area under the receiver operating characteristic (roc) curve of pocus was 0.890 (95% ci, 0.844 to 0.926). conclusion: it seems that pocus can be applied in screening patients with mcl tears following blunt knee trauma. keywords: medial collateral ligament, knee; ultrasonography; magnetic resonance imaging; emergency service, hospital cite this article as: ahmadi o, heydari f, golshani k, derakhshan s. point-of-care ultrasonography for diagnosis of medial collateral ligament tears in acute knee trauma; a diagnostic accuracy study. arch acad emerg med. 2022; 10(1): e47. https://doi.org/10.22037/aaem.v10i1.1480. 1. introduction the medial collateral ligament (mcl) is one of the four major ligaments of the knee (1). it extends from the medial femoral epicondyle to the medial tibial condyle and medial surface of its body (2). the superficial mcl is the most commonly damaged ligament of the knee after direct knee trauma and is mostly caused by valgus stress (3). an mcl injury is a sprain or tear to the medial collateral ligament (4). it is usually diagnosed through physical examination of the knee (5). but initial pain and swelling sometimes make it very difficult to judge the severity of the ∗corresponding author: farhad heydari; department of emergency medicine, alzahra hospital, sofeh ave, keshvari blvd., isfahan, iran.email: farhad_heidari@med.mui.ac.ir, phone: +989131367643, orcid: https://orcid.org/0000-0002-6296-0045. injury; therefore, it is important to use an imaging modality to confirm the diagnosis (6, 7). early and accurate diagnosis of mcl injury is very important for determining the suitable treatment to return to function in a short time (4, 8). mri has been considered as the non-invasive diagnostic gold standard modality, but it is costly, not available in all centers, and needs long waiting periods (5, 9). also, mri has major limitations and cannot be used for those with metal implants, indwelling cardiac pacemakers, and claustrophobia (10, 11). recent studies showed that point-of-care ultrasound (pocus) is an alternative, portable, non-invasive, and real-time imaging modality for evaluating the soft tissue pathology of the knee (9, 10, 12-14). pocus is easier to access, has lower costs, and is quicker than mri for diagnosis of mcl tear (3, 5). therefore, the use of pocus for identifying mcl tears has increased in recent years. this study aimed to assess the accuracy of pocus in diagnosis of mcl tears in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. ahmadi et al. 2 comparison with mri, as the gold standard reference. 2. methods 2.1. study design and setting this prospective cross-sectional study was conducted between 2020 and 2021 in the emergency department (ed) of kashani hospital, isfahan, iran. the study received ethics approval from the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1397.091). all patients were included after obtaining written informed consent. researchers adhered to ethical principles of declaration of helsinki and confidentiality of patients’ information. 2.2. participants all patients with acute knee injuries and suspected acute mcl injury following blunt trauma based on clinical examination findings were included in the study. suspected acute mcl injury has been defined as medial knee pain, tenderness, and swelling following acute blunt knee trauma (trauma in the last 3 days). using convenience sampling, patients were enrolled 24 hours a day during all days of the week. patients younger than 18 years, those with multiple trauma, unstable hemodynamics, loss of consciousness, history of a previous mcl tear or previous injury on the injury site, diagnosis of a fracture in the knee, and contraindications to mri, and those who declined to participate in the study and refused to continue treatment and orthopedic follow-up were excluded. 2.3. study protocol after history taking and primary physical examination, twoview radiographic imaging (ap and lateral x-ray) of the knee was performed. if there was no fracture in the knee x-ray, the point-of-care sonographic (pocus) examination on the knee was carried out by one of the four trained emergency medicine specialists. each sonographer received two hours of theoretical and two hours of practical instructions by a radiologist who was an expert in musculoskeletal us. after the pocus examination, the us findings were recorded on data collection sheets. the injured knee was always treated with a cylindrical splint of the lower limb. all of the patients were asked to refer to an orthopedic clinic with prior coordination and arrangement 7-10 days after discharge from ed. second pocus was done in the orthopedic clinic and then the patient was examined by a specific orthopedic specialist who was blinded to the pocus results. ultrasounds were performed by two different sonographers. after that, mri was performed. the diagnosis of mcl tear was made based on mri findings. the radiologists who were blinded to the pocus findings evaluated the mri. the mri machine used in this study was ge tesla (general electric company of america). the collected variables included age, sex, clinical findings, first and second pocus, and mri findings were recorded on data collection forms. finally, pocus findings were compared to mri findings in diagnosing mcl injury. 2.4. ultrasound technique ultrasound was performed using philips affiniti 50g ultrasound machine with liner probe (5-12 mhz). the ultrasound examination was done in prone position with 20-30 degrees of knee flexion and slight external rotation of the hip joint. the transducer was placed on a longitudinal plane at the medial aspect of the knee at the mcl site. mcl with hyperechoic and fibrillar structure in a longitudinal plane was considered intact, while thickening and heterogeneously hypoechoic changes in the mcl were considered as injured mcl (3, 5). 2.5. statistical analysis the sample size was calculated at the confidence interval of 95%, with sensitivity of 84.6% based on the results of a previous study (9), and the error level of 0.06. thus, the required sample size was 244. finally, the collected data was entered into spss software (ver. 25) and was presented as number (%) or mean ± standard deviation (sd). accuracy, sensitivity, specificity, positive predictive value (ppv ), and negative predictive value (npv ) of pocus for the identification of mcl tear were calculated. 3. results 3.1. baseline characteristics of studied cases a total of 315 patients with suspected mcl injury after acute blunt knee trauma were initially assessed for eligibility, 55 of whom were excluded. thus, two hundred and sixty patients were enrolled in the study. then ten patients did not undergo mri due to the lack of orthopedic follow-up. finally, 250 patients with a mean age of 25.05 ± 9.12 years were studied (86.8% male). the study flow diagram is shown in figure 1. the patients’ demographic and clinical findings are presented in table 1. according to the mri findings, as the gold standard, 55(22.0%) patients had mcl injury, while pocus showed that 57 (22.8%) patients had mcl injuries (table 1). 3.2. screening performance characteristics in comparison with mri scans, the sensitivity, specificity, ppv, npv, and accuracy of ultrasonography in the detection of mcl injury were 83.64 (95% ci, 71.20 to 92.23), 94.36% (95% ci, 90.13 to 97.15), 80.70% (95% ci, 69.95 to 88.25), 95.34% (95% ci, 91.83 to 97.38), and 92.00% (95% ci, 87.92 to 95.05), respectively. the area under the receiver operating this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e47 figure 1: consort flow diagram of patient enrollment. table 1: baseline characteristics of the studied patients variable value gender male 217 (86.8) female 33 (13.2) age (year) mean ± sd 25.05 ± 9.12 clinical findings of knee pain 250 (100) tenderness 248 (99.2) swelling 226 (90.4) mcl tear on ultrasonography yes 57 (22.8) no 193 (77.2) mcl tear on mri yes 55 (22.0) no 195 (78.0) data are presented as mean ± standard deviation (sd) or frequency (%). mcl: medial collateral ligament; mri: magnetic resonance imaging. characteristic (roc) curve of the pocus exam in the detection of mcl injuries was 0.890 (95% ci, 0.844 to 0.926). the sensitivity, specificity, ppv, npv, and accuracy of the second pocus exam after one week are shown in table2. 4. discussion in the current study, sensitivity, specificity, ppv, npv, and accuracy of us in diagnosis of mcl tears following acute blunt knee trauma, as compared to mri, were 83.64%, 94.36%, 80.70%, 95.34%, and 92.00%, respectively. recently, the us exam has been widely used as a screening musculoskeletal imaging modality. the advantages of ultrasound include safety, saving health care costs, ease of use, and portability of the equipment. however, there are limitations to the use of ultrasound, such as dependence on operator’s training, skills, and experience. the us has been used for detecting knee injuries in various studies with different results (15). therefore, in the current study, the accuracy of pocus in diagnosis of mcl tears was evaluated. the mean age in the present study was 25 years and 217 participants were male (86.8%), which were similar to previous studies (9-11). the males are more likely to have traumatic knee injuries because they are more physically active during the day (9). according to the mri findings, 55(22.0%) patients had mcl injuries. a study on sixty patients with clinically suspected meniscal/ligamentous injury of the knee demonstrated that 13 patients had mcl injuries based on mri (9). ghosh et al. evaluated 9 patients with medial knee pain scheduled for a knee mri (3). they had three cases with mcl pathology on mri (1 chronic and 2 acute). the prevalence of mcl injury in these studies is similar to the present study. in the current study, sensitivity, specificity, ppv, npv, and accuracy for the us, as compared to mri, in diagnosis of mcl tears were 83.64%, 94.36%, 80.70%, 95.34%, and 92.00%, respectively. consistent with the results of the present study, singh et al. demonstrated that sensitivity, specificity, and accuracy of ultrasound in diagnosis of mcl injuries, compared with mri were 84.6%, 100%, and 96.6% (9). in another study, the us had 83.33% sensitivity 97.73% specificity, and 96% accuracy for mcl tears (10). these results are compatible with the current study. ghosh et al. showed that us had a sensitivity of 67%, and specificity of 83%, ppv of 67%, and npv of 83% for identifying mcl tears (3). they evaluated acute and chronic knee injuries and only subjects with chronic mcl changes were missed on ultrasound. they suggested that the us may have a limited role in evaluating chronic ligamentous injuries. in a study performed by najafi et al., the sensitivity, specificity, ppv, npv, and accuracy of us in diagnosis of complete mcl tears were 66%, 98%, 50%, 99%, and 97%, respectively (5). in this study, which was performed in a referral sports medicine center for arthroscopic candidate patients with acute and chronic knee trauma, a small proportion of patients had complete mcl tears; therefore, the results could not be generalized. in the present study, the specificity slightly decreased after one week (94.36% and 93.33%). despite the low sensitivity of us in diagnosis of chronic mcl ligament injuries, it is a useful tool for the immediate diagnosis of acute mcl injuries in selected subjects, for whom mri is contraindicated, or when mri is not available, so that treatment can be started earlier. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. ahmadi et al. 4 table 2: diagnostic value of ultrasound in diagnosis of medial collateral ligament injury in emergency department on admission (first) and one week after the injury (second) mri first ultrasound second ultrasound positive (n=57) negative (n=193) positive (n=59) negative (n=182) positive (n= 55) 46 9 46 9 negative (n= 195) 11 184 13 182 screening performance characteristics characteristic first ultrasound second ultrasound auc 0.890 (0.844 0.926) 0.885 (0.839 – 0.922) sensitivity 83.64 (71.20 92.23) 83.64 (71.20 92.23) specificity 94.36 (90.13 97.15) 93.33 (88.87 96.40) positive predictive value 80.70 (69.95 88.25) 77.97 (67.39 85.84) negative predictive value 95.34 (91.83 to 97.38) 95.29 (91.74 97.35) negative likelihood ratio 0.17 (0.09 to 0.32) 0.18 (0.09 0.32) positive likelihood ratio 14.83 (8.25 26.64) 12.55 (7.33 21.49) accuracy 92.00 (87.92 – 95.05) 91.20 (86.98 94.40) data was expressed with 95% confidence interval. auc: area under the receiver operating characteristic (roc) curve; mri: magnetic resonance imaging. finally, pocus is a highly sensitive, specific, and accurate modality for acute mcl tears. this study examined the role of pocus as an initial first-line modality in the evaluation of mcl tears. for patients with clinical suspicion to mcl injury, pocus was suggested as an initial imaging tool of choice. mri can be recommended as the next line modality for further evaluation. 5. limitations there are limitations in the present study. this was a singlecentered study with limited generalizability. it was better to perform it with a larger sample size as well as in several centers. also, only mcl was examined. to determine the simultaneous medial meniscus tear, it was better to evaluate the internal compartment of the knee with ultrasound. 6. conclusion the present study found that pocus is a useful adjuvant diagnostic modality for evaluating mcl tears. pocus helps in taking a decision regarding management of an mcl tear, while the patient can avoid undergoing the costly and timeconsuming confirmatory mri if the result is negative, unless they do not improve during the follow-up period. therefore, pocus is recommended as a useful initial modality in patients with suspected mcl injuries. 7. declarations 7.1. acknowledgments the authors appreciate the insightful cooperation of the staff of the emergency department of kashani hospital, isfahan, iran. 7.2. authors’ contributions o.a., f.h., k.g., s.d.; contributed to conception and design. o.a., f.h., s.d.; contributed to the all-experimental works, data gathering and statistical analyses, as well as interpretation of data. o.a., f.h.; were responsible for overall supervision. f.h.; drafted the manuscript, revised by o.a., k.g. and s.d. all authors performed editing and approving the final version of this paper for submission. they also participated in the finalization of the manuscript and approved the final draft. 7.3. funding and supports this study was funded by isfahan university of medical sciences. 7.4. competing interests the authors declare no conflict of interest. 7.5. ethics approval and consent to participate ethical approval was obtained from the ethics committee of isfahan university of medical sciences (ir.mui.med.rec.1397.091). references 1. tsai w-h, chiang y-p, lew rj. sonographic examination of knee ligaments. am j phys med rehabil. 2015;94(8):e77-e9. 2. lee mj, chow k. ultrasound of the knee. semin musculoskelet radiol. 2007;11(2):137-48. 3. ghosh n, kruse d, subeh m, lahham s, fox j. comparing point-of-care-ultrasound (pocus) to mri for the dithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e47 agnosis of medial compartment knee injuries. j med ultrasound. 2017;25(3):167-72. 4. andrews k, lu a, mckean l, ebraheim n. review: medial collateral ligament injuries. j orthop. 2017;14(4):550-4. 5. najafi j, bagheri s, lahiji fa. the value of sonography with micro convex probes in diagnosing meniscal tears compared with arthroscopy. j ultrasound med. 2006;25(5):593-7. 6. marchant mh, tibor lm, sekiya jk, hardaker wt, garrett we, taylor dc. management of medial-sided knee injuries, part 1:medial collateral ligament. am j sports med. 2011;39(5):1102-13. 7. cook jl, cook cr, stannard jp, vaughn g, wilson n, roller bl, et al. mri versus ultrasonography to assess meniscal abnormalities in acute knees. j knee surg. 2014;27(4):319-24. 8. encinas-ullán ca, rodríguez-merchán ec. isolated medial collateral ligament tears: an update on management. efort open rev. 2018;3(7):398-407. 9. singh a, mangat i, thukral c, gupta k. diagnostic accuracy of ultrasonography in evaluation of knee injuries with magnetic resonance imaging correlation. int j anat radiol surg. 2018;7(1):50-5. 10. singh b, pawar kn, kachewar s, ghule ss, lakhkar dl. evaluation of knee joint by ultrasound and mri. iosr j dent med sci. 2016;15(10):122-31. 11. el-monem sa, enaba mm. comparative study between high resolution ultrasound (hrus) and mri in diagnosis of meniscal and cruciate ligaments injury of the knee. med j cairo univ 2012;80(2):233-42. 12. zamani m, mazaheri m, heydari f, masoumi b. comparison of diagnostic accuracy of bedside ultrasonography and radiography for calcaneal fractures in the emergency department. j emerg pract trauma. 2021;7(1):17-21. 13. artul s, khazin f, hakim j, habib g. ultrasonographic findings in a large series of patients with knee pain. j clin imaging sci. 2014;4:45-. 14. ahmadi o, motififard m, heydari f, golshani k, azimi meibody a, hatami s. role of point-of-care ultrasonography (pocus) in the diagnosing of acute medial meniscus injury of knee joint. ultrasound j. 2022;14(1):1-8. 15. makhmalbaf h, shahpari o. medial collateral ligament injury; a new classification based on mri and clinical findings. a guide for patient selection and early surgical intervention. arch bone jt surg. 2018;6(1):3-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e55 or i g i n a l re s e a rc h ethanol sclerotherapy versus laparoscopic surgery in management of ovarian endometrioma; a randomized clinical trial hatav ghasemi tehrani1, raheleh tavakoli1, maryam hashemi1∗, somayeh haghighat2 1. department of obstetrics and gynecology, school of medicine, isfahan university of medical sciences, isfahan, iran. 2. physiology research centre, kashan university of medical sciences, isfahan, iran. received: may 2022; accepted: june 2022; published online: 7 july 2022 abstract: introduction: a variety of therapeutic modalities are available in management of ovarian endometrioma. this study aimed to compare the effects of ethanol sclerotherapy and laparoscopic surgery on disease recurrence and ovarian factors of these patients. methods: 70 women with ovarian endometrioma and chronic pelvic pain were randomly divided into two groups. the first group underwent sclerotherapy with a puncture needle (cook) and the second group underwent laparoscopic surgery. both groups were followed up every three months to investigate the recurrence rate. in this regard, ultrasonography was performed 3 months and 12 months after treatment, and serum anti-müllerian hormone (amh) levels were also reassessed 12 weeks after the intervention. results: 70 women with the mean age of 31.46 ± 4.71 years, and the mean body mass index (bmi) of 23.12 ± 1.01 were studied. the two groups were similar regarding age (p = 0.770), bmi (p = 0.371), history of gastrointestinal signs (p = 0.794), history of urinary diseases (p = 0.324), dysmenorrhea (p = 0.403), pelvic pain (p = 0.454), dyspareunia (p = 0.448), location of cyst (p = 0.448), and diameter of cyst (p = 0.250). in the laparoscopic group, a significant decrease in anti-müllerian hormone (amh) levels was observed after 12 weeks (p < 0.0001), while in the sclerotherapy group, no significant changes were found between pre-and post-operative amh levels (p = 0.120). cyst size decreased significantly in both groups three months (p < 0.001) and twelve months (p < 0.0001) after treatment. in the third month, 8 patients in the sclerotherapy group and 13 patients in the laparoscopic group had recurrences, and in the twelfth month, 17 patients in the sclerotherapy group and 15 patients in the laparoscopic group had recurrence of symptoms (p > 0.05). conclusion: although amh level and mean cyst diameter were significantly lower one year after laparoscopy, recurrence rate of ovarian endometrioma was similar between ethanol sclerotherapy and laparoscopy methods. keywords: endometriosis; ethanol; laparoscopy; ovarian cysts; sclerotherapy cite this article as: ghasemi tehrani h, tavakoli r, hashemi m, haghighat s. ethanol sclerotherapy versus laparoscopic surgery in management of ovarian endometrioma; a randomized clinical trial. arch acad emerg med. 2022; 10(1): e55. https://doi.org/10.22037/aaem. v10i1.1636. 1. introduction one of the most common medical conditions in women is endometriosis, defined as the growth of endometrial tissue outside the uterine cavity, which can respond to hormonal stimulation of the ovaries (1). statistics have revealed that the presence of endometrial glands and stromal tissue outside ∗corresponding author: maryam hashemi; department of obstetrics and gynecology, school of medicine, isfahan university of medical sciences, isfahan, iran. email: maryam.hashemi@med.mui.ac.ir, tel: 00989133272570, orcid: http://orcid.org/0000-0002-7999-2991. the uterine can cause infertility among women of reproductive age (2). endometriosis is widely observed in the pelvic areas such as the ovaries, rectovaginal septum lesion, posterior cul-de-sac, and sacro-uterine ligament (3). ovarian endometrioma is characterized by excessive proliferation of fibroblasts (4). a variety of therapeutic modalities are available in the management of women with ovarian endometrioma, based on medical criteria. for example, medical treatments can be useful for the relief of mild to moderate pain (5). however, surgical approaches are the gold standard in the treatment of infertility and severe pain caused by endometriosis (5). currently, the conservative laparoscopy approach is used as a minimally invasive technique for the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ghasemi tehrani et al. 2 treatment of infertility related to ovarian endometrioma (6). during laparoscopy, either ovarian cyst excision or bipolar coagulation of the internal layer of the cyst wall is applied in most cases (7, 8). regarding laparoscopic excision, after separation of adhesions, an incision is made, and endometriotic lesions are aspirated gently with minimal damage to the unaffected ovarian tissue (7). however, the mentioned methods for treating ovarian endometrioma have many disadvantages, which can affect ovarian function. surgery-related damage to ovarian reserve following laparoscopy has become a central issue, and it seems clear that another option needs to be found (9). therefore, various studies have been performed in order to use safer and less invasive methods to treat this medical condition. one of the newest treatment modalities is ultrasound-guided sclerotherapy (10). chemical sclerotherapy has been successfully performed in various organs, such as cystic lesions of the thyroid nodules, lymphatic malformations of the neck, liver, kidney, and spleen (11-14). sclerotherapy is also used in ovarian endometrioma, and the overall recurrence rate is estimated at 13.8% (15). various sclerosing agents have been used in sclerotherapy, including tetracycline, methotrexate, and ethanol (15). one of the main advantages of this technique, compared with the other techniques, is that it dramatically reduces pelvic pain related to endometriosis, while it has no negative effect on the number of oocytes retrieved and embryo quality (16). however, due to the variety of treatment modalities and different types of surgery methods and their effects on disease recurrence and ovarian reserve, it is still not possible to decide on the best treatment method. the present study aimed to compare the effects of ethanol sclerotherapy and laparoscopic surgery on disease recurrence and ovarian factors of the mentioned patients. 2. methods 2.1. study design and setting this clinical trial was conducted in shahid beheshti hospital, isfahan, iran from december 2020 to january 2022. the study protocol was approved by the ethical committee of isfahan university of medical sciences (code: ir.mui.med.rec.1398.499) and registered on the iranian registry of clinical trial (irct registration id: irct20171030037093n31). participants were informed about the objectives of the study, and informed consent was obtained from all patients before any intervention. 2.2. participants women who had previously been diagnosed with ovarian endometrioma based on clinical examination or imaging were eligible for inclusion. inclusion criteria were as follows: 1) infertile women with ovarian endometrioma diagnosed by ultrasonography or magnetic resonance imaging (mri); 2) age range of 18 to 40 years old; 3) tumor marker ca125 <200 iu/ml; 4) chronic pelvic pain; 5) ovarian endometrioma cysts of 4-10 cm in diameter. in this study, infertility was defined as the failure to achieve a clinical pregnancy after 12 months or more. patients with incomplete information, women with non-endometrial ovarian masses, participants with a history of any malignancy, and patients who did not sign informed consent forms, were excluded from the study. 2.3. data gathering a standard form was designed in microsoft excel to extract information and patients’ demographic and clinical characteristics, including age, the number of pregnancies, antimüllerian hormone (amh), and any history of gastrointestinal diseases (abdominal pain, nausea, bloating) were recorded. data on pelvic pain was evaluated with the shortform mcgill pain questionnaire (17). 2.4. randomization before the start of the trial, a computer-generated random numbers table was used for randomization, and participants were randomly assigned to experimental groups. 2.5. allocation concealment and blinding allocation concealment was performed using 70 identical, sequentially numbered, sealed envelopes. the study was a double-blind clinical trial. patients and research assistants were blinded to treatment allocation. 2.6. interventions after obtaining consent, participants were randomly divided into two groups (35 cases/group): group 1) sclerotherapy group and group 2) laparoscopy group. in the first group, a standardized approach was followed for sclerotherapy, as previously described by yazbeck et al. (18). transvaginal sclerotherapy was carried out under sedation and using ultrasound guidance in the lithotomic position, using needles of various sizes (cook, bloomington, indiana). the endometrioma lesion was observed and confirmed; following this, the needle tip was inserted into the lesions, and cyst content was aspirated. approximately 80% of the cyst volume, was replaced with a maximum of 100 ml of 95% ethanol. ethanol remained in the lesion for about 20 minutes, and then it was completely aspirated to eliminate the side effects of ethanol. in the second group, laparoscopic cystectomy has performed under general anesthesia. in all patients, after the incision was made into the cyst wall, the content was completely aspirated, and then endometrioma was stripped from the healthy ovarian parenchyma. finally, all endometrial lesions excised this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e55 table 1: comparing the demographic and clinical baseline characteristics between the groups variable sclerotherapy n= 35 laparoscopy n= 35 p-value age (year) 32.17 ± 4.76 30.80 ± 4.63 0.770 body mass index 23.01 ± 1.17 23.22 ± 0.79 0.371 history of gastrointestinal signs 10 (28.57) 11 (31.42) 0.794 history of urinary diseases 7 (20.00) 4 (11.42) 0.324 dysmenorrhea 25 (71.42) 28 (80.00) 0.403 pelvic pain 24 (68.57) 21 (60.00) 0.454 dyspareunia 16 (45.71) 9 (25.71) 0.081 location of cyst right 7 (20.00) 11 (31.42) left 22 (62.85) 17 (47.58) 0.448 bilateral 6 (17.15) 7 (20.00) mean longest cyst diameter (mm) 6.92 ± 1.85 8.67 ± 8.69 0.250 data are presented as mean ± standard deviation or frequency (%). table 2: comparing the outcomes between the two groups outcome sclerotherapy n= 35 laparoscopy n= 35 p-value mean longest cyst diameter (mm) before 6.92 ± 1.85 8.67 ± 8.69 0.250 3 months after 3.30 ± 2.52 1.22± 1.80 <0.001 12 months after 5.45 ± 1.65 3.19 ± 1.98 <0.001 recurrence rate (%) 3 months after 8 (22.8) 13 (28.8) 0.192 12 months after 17 (48.57) 15 (42.85) 0.631 data are presented as mean ± standard deviation or frequency (%). from the abdominal cavity were sent for histological analysis. 2.7. outcomes all patients were hospitalized and monitored for at least 24 hours. both groups were followed up every 12 weeks to investigate the recurrence rate. in this regard, ultrasonography was performed 3 months and 12 months after treatment, and serum amh levels were also reassessed 12 weeks after the intervention. 2.8. statistical analysis the sample size (35/group) was calculated based on the results of previous studies (16, 19) using the formula for estimating the sample size, with a confidence level of 95% (z = 2 – a/1 = 1.96), and a test power coefficient of 84%. statistical analysis was performed using the spss software version 24. the descriptive data were presented as mean ± standard deviation (sd) or frequency (percentage). data were analyzed using chi-square, independent t-test, and pearson correlation statistical test. a p-value <0.05 was considered to be statistically significant. 3. results 3.1. participant flow figure 1 demonstrates details of the enrollment, allocation, follow-up, and analysis of participants through the trial based on the consort criteria (20). 10 women were excluded from the study due to not meeting the inclusion criteria (n = 4), declining to participate (n= 3), not receiving the allocated intervention (n= 1), and being lost to follow up (n= 2). finally, a total of 70 women who had previously been diagnosed with ovarian endometriosis were included in the study. 3.2. baseline characteristics of patients in the present study, 70 women with ovarian endometrioma were randomly divided into two groups. the mean age of the participants was 31.46 ± 4.71 years, and their mean bmi was 23.12 ± 1.01. demographic and clinical baseline characteristics of the study population are illustrated in table 1. there was no significant difference between groups regarding age (p = 0.770), bmi (p = 0.371), history of gastrointestinal signs (p = 0.794), history of urinary diseases (p = 0.324), dysmenorrhea (p = 0.403), pelvic pain (p = 0.454), dyspareunia (p = 0.448), location of cyst (p = 0.448), and diameter of cyst (p = 0.250). the mean cyst volume aspirated and the mean volume of alcohol instilled in the sclerotherapy group were this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ghasemi tehrani et al. 4 figure 1: the consort flow diagram of the studied population. 125.88 ± 110.66 ml and 71.66 ± 30.91 ml, respectively 3.3. outcomes and estimation table 2 compares the outcomes between groups before and after the intervention. in the laparoscopic group, a significant decrease in amh levels was observed after 12 months (2.48 ± 1.34 vs, 1.62 ± 1.22; p < 0.001), while in the sclerotherapy group, no significant changes were found between preand 12-months post-operative amh levels (2.12 ± 1.05 vs. 2.09 ± 1.01; p = 0.120). cyst size significantly decreased in both groups three months (p < 0.001) and twelve months (p < 0.001) after treatment. in the third month, 8 patients in the sclerotherapy group and 13 patients in the laparoscopic group had recurrences, and in the twelfth month, 17 patients in the sclerotherapy group and 15 patients in the laparoscopic group had recurrence of symptoms. based on the statistical analysis, no significant differences were found in terms of recurrence rate between the two groups. 4. discussion based on the findings of the present study, although amh level and mean cyst diameter were significantly lower one year after laparoscopy, recurrence rate of ovarian endometrithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e55 oma was similar between ethanol sclerotherapy and laparoscopy methods. endometriosis is a benign disease characterized by the growth of endometrial tissue outside the uterine cavity (21). the most common affected sites for endometriosis are ovaries (1). in the management of ovarian endometriosis, the patient’s symptoms, fertility status, and the extent of lesion, are of particular importance. the best method to evaluate the severity and extent of the lesion is laparoscopic surgery, which is preferable to laparotomy for treatment because it creates little adhesion (22). however, the laparoscopic procedure was associated with problems, including surgery-related damage to ovarian reserve and a high recurrence rate of endometrioma after treatment (23). in this regard, sclerotherapy was introduced as a new method for the management of ovarian endometrioma. in the present study, a significant decrease in amh levels was observed after 12 weeks in the laparoscopy group. this lends support to the previous findings in the literature (23-26). a comprehensive study by raffi et al. showed that laparoscopic surgery of endometrioma lesions reduced antimüllerian hormone levels, which may be one of the reasons for the reduced fertility rate in these women after surgery (23). on the other hand, in line with the report by huang et al. (27), the serum level of amh in the sclerotherapy group had not changed in our study, so our experiments demonstrate that sclerotherapy might be safer and less invasive than laparoscopy. in this research, recurrence was defined as the presence of a typical cystic mass with a minimum diameter of 20 mm, detected by transvaginal ultrasonography within three months after the surgery. although studies have suggested that ethanol sclerotherapy could be an effective strategy for the treatment of ovarian endometrioma from the standpoint of recurrence (28, 29), we did not find a significant difference in recurrence rates between the two groups in this study. this difference in findings may be due to several different factors, such as methodological differences. however, it seems that the chances of pregnancy will increase due to the improvement of amh levels in the sclerotherapy group. cyst size significantly decreased in both groups three months and twelve months after treatment, compared to before treatment. our results share a number of similarities with chang et al.’s (30) findings, in which the authors showed that cyst size was consistently decreased until six months after sclerotherapy. based on our study, ethanol sclerotherapy seems to be an effective alternative in the management of ovarian endometrioma and also appears to decrease surgery-related damage to ovarian reserve. 5. limitations the current study was limited by a small sample size and possible selection bias because of the specificity of the study design, so further studies are needed to increase the generalizability of its findings. in addition, the result might be affected by the involvement of different surgeons and the different laboratory conditions. 6. conclusion based on the findings of present study, although amh level and mean cyst diameter were significantly lower one year after laparoscopy, recurrence rate of ovarian endometrioma was similar between ethanol sclerotherapy and laparoscopy methods. therefore, ethanol sclerotherapy seems to be an effective alternative for laparoscopic surgery in management of ovarian endometrioma. 7. declarations 7.1. acknowledgments this research was made possible by a grant from isfahan university of medical science. 7.2. availability of data and materials all data supporting the findings of the article and materials used in this work were publicly available. 7.3. data availability the data is at the disposal of the corresponding author of the article and it it can be made available to the researchers upon request. 7.4. authors’ contributions conceptualization and supervision: hatav ghasemi tehrani, maryam hashemi methodology: hatav ghasemi tehrani, raheleh tavakoli data collection: raheleh tavakoli data analysis: somayeh haghighat writing, review and editing: all authors 7.5. funding and supports this study was supported by grants from isfahan university of medical sciences (398662). 7.6. conflict of interest the authors declare that there is 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askary e, keramati p, moradi alamdarloo s, poordast t, ashraf ma, et al. assisted reproductive technique outcomes in patients with endometrioma undergoing sclerotherapy vs laparoscopic cystectomy: prospective cross-sectional study. reprod med biol. 2021;20(3):313-20. 11. steinl gk, stewart la, mcmanus c, lee ja, kuo jh. ethanol ablation for the treatment of benign thyroid nodules. am j surg. 2022;224(1):408-11. 12. bagrodia n, defnet am, kandel jj. management of lymphatic malformations in children. curr opin pediatr 2015;27(3):356-63. 13. dietrich c, chiorean l, potthoff a, ignee a, cui x, sparchez z. percutaneous sclerotherapy of liver and renal cysts, comments on the efsumb guidelines. z fur gastroenterol. 2016;54(02):155-66. 14. funakoshi h, shirane s, toda j. sclerotherapy using polidocanol foam for a giant splenic cyst. radiol case rep. 2020;15(9):1596-600. 15. kim gh, kim ph, shin jh, nam ic, chu hh, ko hk. ultrasound-guided sclerotherapy for the treatment of ovarian 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parallel group randomised trials. int j surg. 2012;10(1):28-55. 21. martone s, troìa l, marcolongo p, luisi s. role of medical treatment of endometriosis. minerva obstet gynecol. 2021;73(3):304-16. 22. goldberg jm, falcone t, diamond mp. current controversies in tubal disease, endometriosis, and pelvic adhesion. fertil steril 2019;112(3):417-25. 23. raffi f, metwally m, amer s. the impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. j clin endocrinol metab. 2012;97(9):3146-54. 24. mostaejeran f, hamoush z, rouholamin s. evaluation of antimullerian hormone levels before and after laparoscopic management of endometriosis. adv biomed res. 2015;4. 25. deckers p, ribeiro sc, simoes rds, miyahara c, baracat ec. systematic review and meta-analysis of the effect of bipolar electrocoagulation during laparoscopic ovarian endometrioma stripping on ovarian reserve. int j gynaecol obstet. 2017;140(1):11-7. 26. biacchiardi cp, delle piane l, camanni m, deltetto f, delpiano em, marchino gl, et al. laparoscopic stripping of endometriomas negatively affects ovarian follicular reserve even if performed by experienced surgeons. reprod biomed online. 2011;23(6):740-6. 27. huang l, chang m-y, shiau c-s. changes in antimüllerian hormone after ultrasound guided aspiration and ethanol sclerotic therapy of ovarian cyst. taiwan j obstet gynecol. 2021;60(3):509-12. 28. noma j, yoshida n. efficacy of ethanol sclerotherthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e55 apy for ovarian endometriomas. int j gynaecol obstet. 2001;72(1):35-9. 29. rahmani e, aflatoonian a, rahsepar m. assessing the efficacy of aspiration and ethanol injection in recurrent endometrioma before ivf cycle: a randomized clinical trial. iran j reprod med. 2013;11(3):179-84. 30. chang m-y, hsieh c-l, shiau c-s, chiang r-d, chan c-h. ultrasound-guided aspiration and ethanol sclerotherapy (est) for treatment of cyst recurrence in patients after previous endometriosis surgery: analysis of influencing factors using a decision tree. j minim invasive gynecol. 2013;20(5):595-603. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e35 or i g i n a l re s e a rc h methyl prednisolone vs dexamethasone in management of copd exacerbation; a randomized clinical trial mohammad emami ardestani1, elham kalantary1∗, vajihe samaiy1, keramat taherian2 1. department of internal medicine, isfahan university of medical sciences, isfahan, iran. 2. department of emergency medicine, isfahan university of medical sciences, isfahan, iran. received: november 2015; accepted: january 2016; published online: 11 january 2017 abstract: introduction: corticosteroids are routinely used in management of chronic obstructive pulmonary disease (copd) exacerbation.the main purpose of present study was to compare the efficacy of methyl prednisolone (mp) and dexamethasone (dxm) forthis purpose. methods: adult copd patients entered the present clinical trial.all patients received standard treatment on admission andwere then divided into 2 groups of intravenous mp and dxm. patients were asked to rate their shortness of breath; sputum volume and viscosity; dyspnea; cough; and general wellbeing on a 0-5 scale. baseline parameters such as o2 saturation, arterial blood gas parameters, and white blood cell (wbc) count were compared on admission and day 7 and 14 of therapy using spss 22. results: 68 patients were randomly allocated to 2 groups of 34(82.4% male). the baseline characteristics of the two groups were similar (p < 0.05). comparison of treatment outcomes for the 7th day showed a significant difference between the 2 groups only regarding cough (p = 0.047), h c o3 (p < 0.001), and o2 saturation (p = 0.042). onday 14 the 2 groups were different only regarding cough (p = 0.048) and sputum viscosity (p = 0.011). there was a significant difference between the two groups regarding trend of changes in dyspnea (p = 0.02 ; dxm à mp) and cough (p = 0.035; mp à dxm). there were no significant differences between the two medications regarding side effects on 7th and 14th day after treatment. conclusion:it seems that mp and dxm have similar efficacy and side effects in treatment of copd exacerbation and selecting drug of choice would better be based on the most prominent symptoms of patients on admission. keywords: methylprednisolone; dexamethasone; pulmonary disease, chronic obstructive © copyright (2017) shahid beheshti university of medical sciences cite this article as: emami ardestani m, kalantary m, samaiy v, taherian k. methyl prednisolone vs dexamethasone in management of copd exacerbation; a randomized clinical trial. emergency. 2017; 5 (1): e35. 1. introduction chronic obstructive pulmonary disease (copd) is the most prominent cause of morbidity and mortality in developed countriesand has raised to become the third cause of mortality worldwide (1-4). in accordance with international guidelines (gold), the diagnosis of copd should be confirmed with a spirometry result showing a post-bronchodilator value of fev1/ fvc ratio <0.7 (5). the key interventions on copd exacerbationis to control airway inflammation, relieve airflowobstruction and improve ventilation (6). corticosteroids are a large group of drugs used in copd exacerbation and ∗corresponding author: elham kalantary; department of internal medicine, isfahan university of medical sciences, isfahan, iran. tel/fax: 00989133011866; email: elham_kalantari@ymail.com are chosen based on clinical presentations of the patient. it has been shown that using systemic corticosteroids for treating exacerbation of copd leads to reduced failed treatments and improves lung function in the first 72 hours and shortens hospital stay in noncritically ill patients (7-10). different types of corticosteroidswith different characteristics, such as methyl prednisolone (mp) and dexamethasone (dxm), have been used in this regard(11, 12). based on the above-mentioned points, the main purpose of present study was to compare the efficacyof mp and dxm in treatment of copd exacerbation. 2. methods 2.1. study design and settings this is a prospective, randomized, single-blind trial conducted between 2013 and 2014 in al-zahra hospital, isfathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com elham_kalantari@ymail.com m. emami ardestani et al. 2 han, iran. the institutional review board of isfahan university of medical sciences approved the study protocol. all patients gave their written informed consent and the protocol was approved by the hospital’s ethics committee. the researchers adhered to the principles of helsinki declaration over the course of the study. the protocol of the present study was registered on iranian registry of clinical trials under irct number: 2.2. participants all studied patients met the criteria outlined in the guidelines for diagnosis and management of copd, established by the gold standard (13). adult copd patients with acute respiratory distress, increasedcough frequency and severity, increased sputum volume, and/or increased wheezing for 24 hours or more were eligible for entry to the study. patients with history of asthma or atopy, onset of respiratory distress before the age of 35 years, absence of spirometric data, or having received oral or intravenous steroids in the month prior to presentation were excluded. the 68 cases were randomly allocated to two equal groups of 34, using simple randomization method. patients and data analyser were blinded to type of treatment. 2.3. intervention on admission to ed, oxygen therapy was performed until o2 saturation raised to above 88-90%. in addition, all individuals in both groups received a combination of a macrolide (azithromycin) and a third generation cephalosporin (ceftriaxone); nebulized β2-agonist (salbutamol), anticholinergic agent (ipratropium bromide), and inhaled corticosteroid (budesonide). they were then divided into 2 groups of mp and dxm for receiving intravenous (iv ) corticosteroid. the mp group received 2 mg/kg/day mp intravenously for 3 days. then the dose was reduced to 40 mg for 3 days and switched to 30 mg/day of oral prednisone, which was tapered every 3 days with 5 mg decrease in dosage. then inhaled budesonide, 400 micrograms, twice a day was prescribed. prednisone was tapered for 2 weeks, and then ceased. inhaled corticosteroid had to be used for at least 3 months continuously. the second group (dxm group) received 0.375 mg/kg dxm per day, and then its dosage was gradually tapered. after 7 to 14 days, the drug was replaced by 30 mg/day methyl prednisone, and continued by the same protocol as mp group. 2.4. assessments patients were assessed within an hour of admission and then every day for two weeks to evaluate the therapeutic effect of treatment and the side effects. questions were asked about shortness of breath; sputum volume and viscosity; dyspnea; cough; and general wellbeing on admission and on every day of therapy. patients were asked to score each symptom from 0 (much better than usual) to 5 (much worse than usual). baseline parameters such as o2 saturation, arterial blood gasparameters, andwhite blood cell (wbc) count were evaluated on admission and on day 7 and 14 of therapy. potential corticosteroid side effects such as mood changes, heartburn, overt gastrointestinal bleeding, and blood sugar disturbance were recorded in every visit. 2.5. statistical analysis sample size was calculated to be 33 in each group based on zα = 1.96, zβ = 0.84, s = 12.4, and d = 8.6. all data from the patients were analysed using independent sample ttest or mann-whitney u test for quantitative variables and chisquare test for qualitative variables. chisquare for trend analysis was used to compare trend of changes in sputum volume and viscosity as well as dyspnea and cough between the two groups.a value of p < 0.05 was consideredto indicate statistical significance. all data are reported as mean ± standard deviation (sd). analyses were done using spss software version 22.0 (spss inc, chicago, il). 3. results 68 copd patients were randomly allocated to 2 equal groups of dxm (82.3% male) and mp (82.4% male). the mean age of dxm and mp groups were 74.67 ± 1.79 and 73.35 ± 2.25 years, respectively (p = 0.648). baseline characteristics of the two groups were compared in table 1. there were no significant differences between the two medications regarding side effects on 7th and 14th day after treatment (table 2). outcome of studied groups on 7th and 14th days after treatment were presented in table 3 and figure 1. 7-day treatment outcome comparison of treatment outcomes for the 7th day showed a significant difference between the 2 groups only regarding cough (p = 0.047; remission: mp: 23 (67.7%) vs. dxm: 16 (48.5%) ), hco3 (mp: 22.58 ± 3.62 vs dxm: 25.66 ± 2.82; p < 0.001), and o2 saturation (mp: 87.71 ± 3.15 vs dxm: 89.24 ± 2.88; p = 0.042). 14-day treatment outcome comparison of treatment outcomes for the 14th day showed a significant difference between the 2 groups only regarding cough (p = 0.048; remission: mp: 27 (79.4%) vs. dxm: 25 (75.7%) ) and sputum viscosity (p = 0.011; remission: mp: 34 (100%) vs. dxm: 24 (72.7%) ). trend of changes there were not any significant differences between the 2 groups regarding trend of changes in sputum volume (p = 0.05), sputum viscosity (p = 0.24), o2 saturation (p = 0.87), p ac o2 (p = 0.83), h c o3 (p = 0.12), serum ph (p = 0.42), wbc count (p = 0.24), on 7thand 14th day after treatment. there was a significant difference between the two groups regarding trend of changes in dyspnea (p = 0.02; dxm àmp) and cough (p = 0.035; mp à dxm). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e35 table 1: baseline characteristics of the patients in the two groups variables dexamethasone methylprednisolone p duration of disease years 8.02 ± 5.25 8.64 ± 4.61 0.608 shortness of breath none 4 (11.8) 0(0) 0.792 mild 3 (8.8) 6 (17.6) moderate 7 (20.6) 8 (23.5) severe 20 (58.8) 20 (58.8) cough none 4 (11.8) 0(0) 0.556 mild 2 (5.9) 3 (8.8) moderate 9 (26.5) 11 (32.4) severe 19 (55.9) 20 (58.8) sputum volume none 8 (23.5) 0(0) 0.081 mild 5 (14.7) 8 (23.5) moderate 5 (14.7) 5 (14.7) severe 16 (47.1) 21 (61.8) high sputum viscosity yes 18 (52.9) 21 (61.8) 0.624 no 16 (47.1) 13 (38.2) o2 saturation on arrival 79.26 ± 6.61 78.65 ± 8.24 0.734 paco2 on arrival 64.85 ± 10.00 64.85 ± 12.52 1.000 hco3 on arrival 26.55 ± 5.37 27.76 ± 5.52 0.365 ph on arrival 7.32 ± 0.04 7.30 ± 0.05 0.218 white blood cell count/mm3 before treatment 8.49±3.6 7.35±3.08 0.164 4. discussion the findings of this study demonstrated that although both treatments are effective and similar in most treatment characteristics, mp is better for reducing cough, and sputum viscosity, while dxm showed a significantly better trend regarding dyspnea treatment and increased o2 saturation, more significantly on the 7th day. although a significant difference was detected between the 2 groups regarding h c o3, it is not clinically significant. despite accepted effects of corticosteroids on airflow obstruction relief and being usedsince 1950, drug of choice, optimal dose, and duration of treatment remain unclear(14). several studieshave demonstrated that corticosteroids can significantly improve patients symptoms and lung function (15-18). li et al. had compared mp with dxm, with the same dosage as this study, in acute exacerbation of copd and believed that dxm was less effective than mp, as cough and sputum in mp group were relieved more quickly than dxm group (6). the present study also showed a significant difference in cough relief in mp group. yet, although the change in trend was similar in both groups, mp group showed significantly better sputum viscosity remission only on the 14th day. zhao et al. also compared these drugs in severe pediatric asthmatic bronchitis and concluded that mp is superior to dxm for this purpose. however, in contrast to the present findings, they demonstrated that mp retrieves hypoxia quickly (19). li et al. also demonstrated that, there was no striking difference in blood gas improvement between the two groups, although the effect of mp seemed slightly superior to that of dxm (6). this is in contrast to our results showing higher o2 saturation on the 7th day in dxm group. andre et al. compared mp and dxm in premature infants who were at risk of chronic lung diseases and concluded that mp is as efficient as dxm with fewer side effects (20). in this study, we found that they were both effective, but they were not significantly different regarding side effects. dxm has wellknown pharmacologic properties, including duration of action of up to 72 hours, a relatively long half-life, and excellent bioavailability (21). as a result, it has been proffered as an alternative to prednisone thatmay allow shorter treatment regimens and improved compliance. joel kravitz et al. indicated that 2 days of oral dxm is at least as effective as 5 days of prednisone in the treatment of mild to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. emami ardestani et al. 4 table 2: comparison of drug side effects between the two groups on 7th and 14th days complications/side effects number (%) p dexamethasone methylprednisolone gastrointestinal bleeding 7 3 (9.1) 2 (5.9) 0.67 14 3 (9.1) 5 (14.7) 0.71 mood change 7 0 (0) 2 (5.9) 0.49 14 0 (0) 3 (8.8) 0.24 heart burn 7 6 (18.2) 4 (11.8) 0.51 14 9 (27.3) 6 (17.6) 0.39 blood sugar disturbance 7 6 (18.2) 4 (11.8) 0.51 14 9 (27.3) 6 (17.6) 0.39 moderate asthma exacerbation. relapse and treatment failurerates were equivalent in both groups (22). it seems that selection of corticosteroids in copd exacerbation should be performed based on the most prominent symptom of patients. in cough prominent cases, mp seems to have better effects and in sputum prominent cases, dxm is superior. 5. limitations single blinding (drug administrator was not binded), lack of long term follow-up regarding times of readmission with exacerbation, and qualitative measurement based on patientdeclaration are among the most important limitations of present study. 6. conclusion our study showed that mp and dxm have similar efficacy and side effects in treatment of patients with copd exacerbation and selectingdrug of choicewouldbetter be basedon the most prominent symptoms of patients. 7. appendix 7.1. acknowledgements the authors would like to thank the staff of alzahra hospital, isfahan, iran. 7.2. funding none. 7.3. conflict of interest none. 7.4. author contribution all authors met the four criteria of authorship as recommended by international committee of medical journal editors. references 1. sutherland er, martin rj. airway inflammation in chronic obstructive pulmonary disease: comparisons with asthma. journal of allergy and clinical immunology. 2003; 112(5): 819-27. 2. murray cj, lopez ad. alternative projections of mortality and disability by cause 19902020: global burden of disease study. the lancet. 1997; 349(9064): 1498504. 3. rafael l, mohsen n, kyle f. global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. lancet. 2012;380:2095-128. 4. burney pg, patel j, newson r, minelli c, naghavi m. global and regional trends in copd mortality, 19902010. european respiratory journal. 2015; 45(5): 123947. 5. vestbo j, hurd ss, agust’ ag, jones pw, vogelmeier c, anzueto a, et al. global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. american journal of respiratory and critical care medicine. 2013; 187 (4): 347-65. 6. li h, he g, chu h, zhao l, yu h. a stepwise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of copd. respirology. 2003; 8(2): 199-204. 7. wood-baker r, gibson p, hannay m, walters e, walters j. systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. the cochrane library. 2005. 8. woods ja, wheeler js, finch ck, pinner na. corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease. international journal of chronic obstructive pulmonary disease. 2014; 9: 421. 9. walters ja, gibson pg, wood-baker r, hannay m, walters eh. systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. the cochrane library. 2009. 10. abroug f, ouanes i, abroug s, dachraoui f, abdallah sb, hammouda z, et al. systemic corticosteroids in acute exacerbation of copd: a meta-analysis of controlled studies with emphasis on icu patients. annals of intensive care. 2014; 4(1): 32. 11. koc i, gogebakan b, bayraktar r, tasdemir d, ozdemir u, adcock i, et al. effects of dexamethasone and antiinflammatory drugs on inflammatory cytokines from bronchial epithelial cells of copd patients. european this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e35 figure 1: failure rate of dexamethasone and prednisolone in treatment of sputum volume (a), sputum viscosity (b), dyspnea (c), and cough (d). respiratory journal. 2015; 46 (suppl 59). 12. sun x, he z, zhang j, deng j, bai j, li m, et al. compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of aecopd. pulmonary pharmacology, therapeutics. 2015; 31: 111-6. 13. pauwels ra, buist as, ma p, jenkins cr, hurd ss, committee gs. global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: national heart, lung, and blood institute and world health organization global initiative for chronic obstructive lung disease (gold): executive summary. respiratory care. 2001; 46(8): 798. 14. bullard mj, liaw s-j, tsai y-h, min hp. early corticosteroid use in acute exacerbations of chronic airflow obstruction. the american journal of emergency medicine. 1996; 14(2): 139-43. 15. davies l, angus r, calverley p. oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. the lancet. 1999; 354(9177): 456-60. 16. sharma r, lettis s, calverley p, barnes n. do inhaled corticosteroids (icss) reduce rate of decline of lung function in copd patients with eosinophil count≥ 2% am j respir crit care med. 2015; 191: a3976. 17. magnussen h, tetzlaff k, bateman ed, watz h, kirsten am, wouters ef, et al. lung-function changes over time following withdrawal of inhaled corticosteroids in patients with severe copd. european respiratory journal. 2015: erj016442015. 18. magnussen h, tetzlaff k, bateman ed, watz h, kirsten am, wouters ef, et al. lung-function changes over time following withdrawal of inhaled corticosteroids in patients with severe copd. european respiratory journal. 2015: erj016442015. 19. zhao h-x, cao m, liu h-y. effect analysis of methylprednisolone in treating the severe children asthmatic bronchitis. jilin medical journal. 2012; 34: 013. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. emami ardestani et al. 6 20. andre p, thebaud b, odievre m, razafimahefa h, zupan v, dehan m, et al. methylprednisolone, an alternative to dexamethasone in very premature infants at risk of chronic lung disease. intensive care medicine. 2000; 26(10): 1496-500. 21. dernedorf h hg, mollmann h. receptor based pharmacokinetics-pharmacodynamics analysis of corticosteroids. j clin pharmacol. 1993; 33: 115-23. 22. kravitz j, dominici p, ufberg j, fisher j, giraldo p. two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial. annals of emergency medicine. 2011; 58(2): 200-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitations conclusion appendix references emergency. 2017; 5 (1): e13 or i g i n a l re s e a rc h deep vein thrombosis among intensive care unit patients; an epidemiologic study mirmohammad miri1, reza goharani1, mohammad sistanizad1,2∗ 1. department of critical care, imam hossein medical and educational center, shahid beheshti university of medical sciences, tehran, iran. 2. department of clinical pharmacy, faculty of pharmacy, shahid beheshti university of medical sciences, tehran, iran. received: march 2016; accepted: jun 2016; published online: 9 january 2017 abstract: introduction: deep vein thrombosis (dvt) is a major cause of morbidity and mortality in intensive care unit (icu) patients despite use of prophylactic anticoagulant therapy. the aim of the present study was to determine the incidence of dvt among medical and surgical icu patients. methods: in this cross sectional study, patients older than 18 years who were hospitalized in the icu of imam hossein educational hospital, tehran, iran, for ≥ 2 days, during august 2008 to july 2011 were evaluated regarding dvt incidence. demographic data, comorbidities, acute physiology and chronic health evaluation (apache) ii scores, icu length of stay, type of dvt prophylaxis, and patient outcomes were analyzed using spss 19. results: out of the 1387 reviewed patient files, 500 (36.04%) patients had been classified as potential dvt cases. dvt occurred in 3.5% of them with the mean age of 60 ± 18 years (62.5% male) and mortality rate of 27.1%. significant independent risk factors of dvt incidence were age (p = 0.02) and length of icu stay (p = 0.01). conclusion: the results of this study showed the 3.5% incidence of dvt in icu admitted patients. longer icu stay and older age were independent risk factors of dvt development. keywords: apache; ultrasonography, doppler; venous thrombosis; intensive care units © copyright (2017) shahid beheshti university of medical sciences cite this article as: haji aghajani m, haddadi m, saadat s. deep vein thrombosis among intensive care unit patients; an epidemiologic study. emergency. 2017; 5 (1): e13. 1. introduction venous thromboembolism (vte) is the third most common cardiovascular disorder after myocardial infarction and stroke (1). the rate of morbidity and mortality associated with thromboembolic events is high, with 28-day fatality rates reported to be 9% for deep vein thrombosis (dvt) and 15% for pulmonary embolism (pe) (2). the causes of dvt may be acquired, inherited or a combination of both (3). the diagnosis and treatment of dvt are challenging and expensive (3). dvt can complicate the course of a disease, but may also be encountered in the absence of precipitating factors. while long-term morbidity due to post-thrombotic syndrome is common, and can be substantial, the major complication is embolization of the thrombus to the lung (4). ex∗corresponding author: mohammad sistanizad; department of critical care, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: +98-9122784895; fax: +98-2188200087; email: sistanizadm@sbmu.ac.ir tensive epidemiological studies of patients with thromboembolism have identified several factors that enhance the risk of dvt development. these include surgery, age, gender, heart failure, history of previous thromboembolism, direct trauma to the leg, use of oral contraceptives, and limb weakness (3, 5). the majority of intensive care unit (icu) patients have one or more risk factors for dvt (3). these patients are further predisposed to dvt during their icu stay due to prolonged immobilization, sepsis, and vascular injury from indwelling central venous catheters or other invasive interventions (6). the incidence of reported dvt is likely to vary across populations, based on baseline characteristics of patients, post-icu admission events and patient condition, clinical suspicion for vte, the scheduling and methods of vte screening, and prophylactic interventions. a retrospective study on icu patients undergoing color-flow doppler sonography for dvt screening has shown an estimated incidence of 33% (5). cross-sectional studies of medical and surgical icu patients have shown that approximately 10% have proximal dvt on admission to the icu (7, 8). one study reports a vte rate of 9 per 10,000 hospital admissions in an irathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. miri et al. 2 nian population (9). based on the above mentioned, the aim of the present study was to determine the incidence of dvt among medical and surgical icu patients. 2. methods 2.1. study design and setting in this retrospective cross sectional study, patients older than 18 years who were hospitalized in icu of imam hossein educational hospital, tehran, iran, for ≥ 2 days were evaluated. the study was conducted in accordance with the principles of the 18th world medical assembly (helsinki, 1964) and all subsequent amendments. the study received ethical approval from shahid beheshti university of medical sciences. 2.2. participants all consecutive patients admitted to the icu for the first time, between august 2008 and july 2011, were considered for inclusion in the study. patients were excluded if they either had a documented dvt/pe before or within 48 hours of icu admission or died or had missing or incomplete data during that time period. in this 21 bed icu, a large variety of medical, surgical, orthopedics, neurosurgical, trauma, cardiac surgery and obstetrics and gynecology patients are managed. the icu care is directed and run by trained intensivists in a semi-closed fashion with an average patient length of stay of 8 days. 2.3. data collection we collected data from patients electronic medical records and a regional icu database. for each patient with clinically and doppler proven dvt, key demographic and clinical characteristics including age, sex, diagnosis on admission, acute physiology and chronic health evaluation ii (apache ii) score, vte prophylaxis regimen, duration of mechanical ventilation, length of icu stay and patient’s outcome (discharge or death) were collected. to provide a uniform and unbiased assessment of doppler proven dvt, one research associate, who was a vascular surgeon, performed the doppler examination for all patients potentially having dvt and was blinded to the patients’ history and clinical status. all clinical decisions were made at the discretion of the icu team. potentially having dvt was defined as international classification of diseases, 9th revision, clinical modification (icd-9cm) codes (453.40, 453.41, 453.42, 453.80, and 453.90). 2.4. statistical analysis all statistical analyses were performed using spss version 19. continuous data were expressed as mean and standard deviation for normally distributed data or median and interquartile range for non-normally distributed data. categorical data were summarized as counts and percentages. continuous data were contrasted between groups using the t-test or rank test as appropriate. categorical data were contrasted using the chi-squared test. multiple logistic regressions were used to identify independent risk factors associated with the presence of dvt. a p value less than 0.05 was considered statistically significant. 3. results: out of the 1387 reviewed patient files during the study period, 500 (36.04%) patients had been diagnosed as potentially having dvt and underwent venous color doppler ultrasonography. table 1 shows the baseline characteristics of patients. based on the results of ultrasonography, 48 (3.5%) cases had dvt (62.5 % male). their mean age was 60 ± 18 years and they had the mean apache ii score of 16.3±5.1 and icu mortality rate of 27.1%. table 2 summarized characteristics of these patients. none of the patients had bleeding or treatment-related complications during the study. univariate analysis showed significant correlation of age (p = 0.02) and length of icu stay with incidence of dvt (p = 0.01) (table 2). based on multivariate analysis, only a longer icu stay significantly associated with dvt incidence (or: 1.07 per each day of icu stay; 95% ci: 1.03-1.22; p value, 0.01). 4. discussion: the results of the present study revealed 3.5 % incidence of dvt in icu admitted patients of imam hossein hospital. dvt is difficult to diagnose because of the poor sensitivity and specificity of clinical symptoms and signs (10). dvt usually originates in the calf veins where the risk of subsequent complications is low. the classic symptoms and signs are due to venous obstruction and an inflammatory response in the affected area. however, the majority of dvt cases remain clinically silent (11). the diagnostic gold standard tools for dvt and pe were venography and pulmonary angiography, both of which are invasive and costly. doppler sonography examination has emerged as the noninvasive imaging method of choice for evaluation of dvt. it has the added ability of being able to visualize other pathologies mimicking venous obstruction (3). the incidence of dvt in this survey is lower than that reported in chinese (19%) and caucasian (2832%) medical icu patients not receiving prophylaxis (12-14). many factors could contribute to this relatively low incidence in comparison to other countries (15). there is an association between age and incidence of dvt (16). the iranian population, like other middle eastern countries, is very young; while about 43% of the western population are 40 years and above, only 18% of iranians are in this age range (17). however, with increasing age of the iranian population, dvt will probably become a growing public health problem. on the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e13 table 1: baseline characteristics of studied patients parameters n (%) apache ii dvt n (%) incidence rate* age (year) ≤40 492(35.47) 13.7 ± 4.7 10 (2.03) 1.64 46 65 391(28.19) 14.4 ± 5 16(4.09) 3.07 ≥66 504(36.34) 18.9 ± 4.2 22(4.37) 3.04 sex male 807(58.18) 17 ± 5.4 30(3.72) 2.84 female 580(41.82) 15.2 ± 4.5 18(3.10) 2.26 icu stay (day) âl’d’7 722(52.05) 15.6 ± 4.7 8(1.11) 2.45 8-28 500(36.05) 16.4 ± 5.9 24(4.80) 3.33 âl’ě29 165(11.90) 16.5 ± 4.2 16(9.70) 1.99 year 2008 263(18.96) 13.1 ± 6.5 7(2.66) 1.92 2009 476(34.32) 16.6 ± 4.5 21(4.41) 3.08 2010 514(37.06) 16.1 ± 5.4 14(2.72) 2.15 2011 134(9.66) 19.5 ± 3 6(4.48) 3.83 * rate per 1000 person days; apache ii: acute physiology and chronic health evaluation ii; dvt: deep vein thrombosis; icu: intensive care unit; data were presented as mean âś standard deviation or number and percentage. table 2: characteristics of cases potentially having deep vein thrombosis (dvt) among intensive care unit (icu) admitted patients variable color doppler ultrasound for dvt p value negative (n=452) positive (n=48) age (year) 51 ± 19 60 ± 18 0.02 gender (male) 259 (57.3%) 30 (62.5%) 0.6 apache ii 14.2 ± 5.4 16.1 ± 4.8 0.2 icu stay (day) 21 ± 31 30 ± 30 0.01 diagnoses acute hemorrhagic stroke 82 (18.1%) 10 (20.8%) 0.7 multiple trauma 124 (27.5 %) 12 (25%) 0.8 respiratory distress 49 (10.8%) 6 (12.5%) 0.7 acute abdomen 45 (9.9%) 5 (10.4%) 0.8 acute ischemic stroke 48 (10.6 %) 5 (10.4%) 0.9 cancer 23 (5.1%) 3 (6.2%) 0.7 sepsis 36 (8%) 3 (6.3%) 0.7 loss of consciousness 24 (5.3%) 1 (2.1%) 0.6 others 21(4.7%) 3 (6.2%) 0.7 type of dvt prophylaxis lmwh 137 (30.3%) 19 (39.6%) 0.5 heparin 191 (42.2%) 12 (25%) 0.05 ipc and gcs 124 (27.5%) 17 (35.4%) 0.5 icu mortality 88 (19.5%) 13 (27.1%) 0.5 apache ii: acute physiology and chronic health evaluation ii; lmwh: low molecular weight heparin; ipc: intermittent pneumatic compression; gcs: graduated compression stockings; dvt: deep vein thrombosis, icu: intensive care unit; data were presented as mean ± standard deviation or number and percentage. other hand, it is likely that increased physician awareness of dvt risk factors and increased utilization of noninvasive imaging have led to a higher diagnosis rate (18). dvt incidence increases rapidly with age in an apparently linear form suggesting a constant incidence and cumulative prevalence, especially in those older than 65 years (1). old age is one of the risk factors in patients with dvt (16). the mean age of patients was almost 60 years, which was within the age range of people prone to venous thromboembolism (over 40 years of age) (1). in addition, consistent with previous studies, which have shown dvt to be more common among men (9), approximately 62.5% of our dvt patients were male. however, length of icu stay was the most significant factor associated with the presence of dvt. the interpretation is that in many patients, dvt developed after they were admitted to the icu and the risk of dvt increased with a longer icu stay. the mean apache ii score was 16.3 ± 5.1 and icu mortality rate was 27.1% (13 in the 48 patients with dvt). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. miri et al. 4 the in-hospital mortality rate, observed in this study, appears similar to those reported from other studies in major academic health centers (2, 19). it is not clear whether this increase in fatality should be attributed to the accompanying risk factors, or to the severity of dvt (proximal), most likely both play an important role (20). we suggest that prophylaxis be administered to those with three or more risk factors. the mortality rate of dvt has a strong association with other risk factors such as, cardiovascular disease, cancer, states following surgery or trauma (2, 21). evidence-based consensus guidelines for vte prophylaxis have been available since a long time ago (22). the american college of chest physicians (accp) guidelines recommend prophylaxis for patients at moderate-to-high risk of vte, using mechanical prophylaxis and/or pharmacological prophylaxis (19, 23). despite the recommendations of international guidelines, physicians often do not prescribe prophylaxis therapy in high-risk situations (24). means to improve dvt prophylaxis should include increasing physicians awareness through training and the implementation of procedures to assess dvt risk during hospitalization, along with the application of evidence-based guidelines for dvt prophylaxis and treatment in both medical and surgical patients (23). there are no local guidelines for dvt prevention in iran. considering that dvt is a serious clinical condition that may lead to patient death, we recommend the assessment of dvt risk (using a risk model assessment form, locally adapted) for all hospitalized patients on admission and during hospitalization. 5. limitations: the main limitation of our study is its retrospective and single center design. prospective multicenter studies are recommended. 6. conclusion: the results of this study showed the 3.5% incidence of dvt in icu admitted patients of imam hossein hospital, tehran, iran. longer icu stay and older age were independent risk factors of dvt development. 7. appendix 7.1. acknowledgements none. 7.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding this research has been supported by a grant by sanofi aventis company. references 1. previtali e, bucciarelli p, passamonti sm, martinelli i. risk factors for venous and arterial thrombosis. blood transfus. 2011;9(2):120-38. 2. cushman m, tsai aw, white rh, et al. deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. am j med. 2004;117(1):19-25. 3. williams mt, aravindan n, wallace mj, riedel bj, shaw ad. 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prevention in colorectal surgery patients. diseases of the colon & rectum. 2006;49(10):1620-8. 20. manafi rasi a, kazemian g, emami moghadam m, et al. deep vein thrombosis following below knee immobilization: the need for chemoprophylaxis. trauma mon. 2013;17(4):367-9. 21. heit ja, o’fallon wm, petterson tm, et al. relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. arch intern med. 2002;162(11):1245-8. 22. hansson po, welin l, tibblin g, eriksson h. deep vein thrombosis and pulmonary embolism in the general population. ’the study of men born in 1913’. arch intern med. 1997;157(15):1665-70. 23. geerts wh, bergqvist d, pineo gf, et al. prevention of venous thromboembolism: american college of chest physicians evidence-based clinical practice guidelines (8th edition). chest. 2008;133(6 suppl):381s-453s. 24. gutt cn, oniu t, wolkener f, mehrabi a, mistry s, bãijchler mw. prophylaxis and treatment of deep vein thrombosis in general surgery. the american journal of surgery. 2005;189(1):14-22. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references archives of academic emergency medicine. 2019; 7 (1): e7 or i g i n a l re s e a rc h impact of education on trauma patients’ handover quality; a before-after trial ali shahrami1, masoomeh nazemi-rafi2∗, hamidreza hatamabadi1, afshin amini1, mahammad haji aghajani3 1. department of emergency medicine, imam hossein hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shahid bahonar hospital, school of medicine, kerman university of medical sciences, kerman, iran. 3. cardiology department, imam hossein hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. received: september 2018; accepted: october 2018; published online: 27 january 2019 abstract: introduction: poor handover and inadequate transmission of clinical information between shifts cause a lot of problems in patient care and result in significant risks for physicians and patients. this study was designed to evaluate the impact of education and application of handover checklist on trauma patients’ handover quality. methods: in this before-after trial, handover process of trauma patients in an educational hospital was evaluated before and after education and application of a handover checklist, abbreviated as “who missed ip?”, using a questionnaire that consisted of 10 necessary items, which should be delivered during handover of trauma patients. a total score of 10 was considered for each patient handover, the score 10 out of 10 indicating that all 10 important pieces of patient information were correctly delivered. results: 52 pre and post-intervention handover sessions were evaluated (438 patients). prior to intervention, 18% of patients were not delivered to the next shift, most of which were in the night shift handover (p < 0.001). from the pre-intervention to the postintervention period, significant improvements were detected in all items except for diagnosis and consulting items. the mean duration of handover changed from 1.22 ± 0.24 minutes to 1.58 ± 0.23 minutes after intervention (p < 0.01). in the pre-intervention period, the score equal or greater than 9 was observed in 7.5% of patients, while after intervention, 63.6% of patients had score ≥ 9 regarding complete handover (p < 0.01). conclusion: based on the findings of the present study, teaching handover standards and application of handover checklist could be helpful in improving the quality of information delivery between emergency medicine residents and improve trauma patients’ handover indices. keywords: clinical audit; emergency service, hospital; patient handoff; checklist; patient safety cite this article as: shahrami a, nazemi-rafi m, hatamabadi h, amini a, haji aghajani m. impact of education on trauma patients’ handover quality; a before-after trial. arch acad emerg med. 2019; 7(1): e7. 1. introduction traumatic injuries are an international issue that affects all aspects of life (1). unfortunately, in developing countries, little attention has been paid to this problem and trauma is the first cause of death and a main cause of disability of active population. emergency department (ed) is a critical area in the healthcare field. in this territory, most of trauma patients are in danger, not only because of the injury, but due ∗corresponding author: masoomeh nazemi-rafi; emergency department, shahid bahonar hospital, gharani avenue, kerman, iran.. e-mail: m_nazemi_r@yahoo.com tel: 00989134936949 to the communication errors between hospital staff (2, 3). weak communication is known as a major factor responsible for 24% of missed diagnoses in ed (2, 4). in trauma patients, more than 10 percent of deaths could be prevented by eliminating theses errors (5). in order to reduce the errors, the joint commission has implemented a standardized method for patients’ handover. however, the complexity and diversity of healthcare makes it impossible to apply a single standard protocol for all hospital sectors. ed has the highest number of patient deliveries; however, in this department, there is still a lack of standard protocols for patients handover (6, 7), especially for trauma patients (3). in a study on trauma patient handover from ed to intensive care unit, it has been demonstrated that a checklist alone was insufficient. they this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. shahrami et al. 2 emphasized the importance of training and standardizing the handover process (3). based on the above-mentioned points, this study was designed to evaluate the impact of education and application of handover checklist on trauma patients’ handover quality. 2. methods 2.1. study design and setting this before-after trial was conducted on the handover process of trauma patients in the emergency department of imam hossein hospital, an educational hospital affiliated to shahid beheshti university of medical sciences, tehran, iran. the pre-intervention survey took place between 31 march and 9 may 2016, while the post-intervention period was performed between 16 may and 24 june. the protocol of study was approved by ethics committee of shahid beheshti university of medical sciences. 2.2. participants all emergency medicine residents present during the handover period of trauma patients at the morning and night shifts participated. there was not any limitation regarding the residents’ age and sex and also trauma severity of patients. 2.3. data gathering a questionnaire that consisted of 10 necessary items, which should be delivered during handover of a trauma patient, including patient’s identification, mechanism of trauma, injury/s, vital signs, findings of history taking and clinical examination, para-clinical findings (imaging and laboratory findings), therapeutic measures, results of consultation with other disciplines, diagnosis, and plan were filled out for handover of all patients before and after education and application of a designed checklist for trauma patients’ handover. a total score of 10 was considered for each patient handover, the score 10 out of 10 indicating that all 10 important pieces of patient information were correctly delivered. a senior emergency medicine resident imperceptibly observed and evaluated the handover process of patients. she was also responsible for data gathering. at the mentioned trauma unit, handovers were performed verbally along with taking notes, among second-year residents. the morning and night handover sessions had little shift overlap, and were from 88:30am and 8-8:30pm. 2.4. developing handover checklist reviewing the related medical literature, observing strong and weak points of real time handover of trauma patients, and with the guidance of experts in the field, the most important and necessary items in the handover process were extracted and used for developing a specific checklist. this mnemonic checklist was introduced on the basis of “who missed ip?” phrase with “who” (patient id as patient’s name, sex, age and pre-injury health status), “m” mechanism of trauma, “i” injury (suspected or sustained), “ss” sign & symptom (containing observations and monitoring), “e” evaluation (imaging, laboratory, etc.), “d” diagnosis, “i” intervention (therapy and consulting), “p” plan for patient management, and “?” giving an opportunity to question in the case of any ambiguity. 2.5. intervention after the first phase (evaluation of patient handover before education and checklist application) and during the weekly conference, the correct ways of handover process were taught to the same residents. after familiarizing these residents with the standards of patient handover and introducing the developed checklist, handover audits were carried out again with the same residents and under the same conditions using the same questionnaire. 2.6. outcome measures the main outcome of this study was evaluating the changes of handover process of trauma patients before and after education and application of checklist. 2.7. statistical analysis data of pre and post-intervention periods were analyzed and compared via spss 21 software. the data were analyzed using t test for quantitative variables and chi-square test or fisher’s exact test for categorical variables. findings were presented as mean ± standard deviation or frequency (%). p < 0.05 was considered as statistically significant. 3. results 26 handover sessions (13 day and 13 night shifts) during each of the pre-intervention and post-intervention phases (52 handover sessions in total) were evaluated (438 patients). prior to intervention, 18% of patients were not handed over, most of which were in the night shifts. this measure was reduced to 6% after intervention (p < 0.001). table 1 shows the situation of information delivery during handover process regarding the 10 studied items. from the pre-intervention to the post-intervention period, significant improvements were detected in all items of the questionnaire except for diagnosis and consulting items. the mean duration of handover changed from 1.22 ± 0.24 minutes to 1.58 ± 0.23 minutes after intervention (p < 0.01). in the pre-intervention period, the score equal or greater than 9 was observed in 7.5% of patients, while after intervention, 63.6% of patients had score ≥ 9 regarding complete handover (p < 0.01). table 2 shows the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e7 table 1: prevalence of handover shortcomings before and after education and application of handover checklist information before (n=199) after (n=239) p value patient identification 116 (58.3) 56 (23.4) < 0.001 trauma mechanism 45 (22.6) 18 (7.5) < 0.001 injury/s 136 (68.3) 89 (37.2) < 0.001 history and examination 115 (57.8) 47 (19.7) < 0.001 vital signs 136 (60.4) 89 (39.6) < 0.001 para-clinic findings 68 (34.2) 43 (18.0) < 0.001 diagnosis 15 (7.5) 29 (12.1) 0.06 therapeutic measures 75 (37.7) 24 (10.0) < 0.001 consult with other disciplines 6 (3.0) 13 (5.4) 0.78 plan 47 (23.6) 34 (14.2) 0.01 data are presented as number (%). table 2: rage of score gained regarding complete handover before and after education and application of handover checklist score range before (n=199) after (n=239) p valve very poor (1-2) 3 (1.5) 0 (0.0) poor (3-4) 39 (19.6) 7 (2.9) fair (5-6) 85 (42.7) 27 (11.3) < 0.001 good (7-8) 57 (28.6) 53 (22.2) very good (9-10) 15 (7.5) 152 (63.6) data are presented as number (%). range of scores obtained regarding complete handover before and after education and application of handover checklist. 4. discussion based on the findings of the present study, teaching handover standards and application of handover checklist could be helpful in improving the quality of information delivery between emergency medicine residents and improve trauma patients’ handover indices. the main aim of each handover is flawless transmission of information (6). to achieve this goal, each hospital department must have its own handover policy. this policy should be chosen by identifying existing problems such as absence of key people, defects in the structure and time allocated to the transmission of information, and responsibility (7). in this study, we established a standardized method for transmitting data by examining the previous status and recognizing its problems and weaknesses. then, after teaching this standardized method to the residents, we evaluated its efficiency in improving the handover quality. we used two methods, at the same time, to improve the handovers: 1designing a pattern for information transmission in the form of acronyms “who missed ip?” to recall items. 2transformation of verbal handover into a written one using the handover checklist. the results of this study showed that a standardized model for handover of trauma patients among emergency residents could lead to an increase in patients’ safety by transmitting true and complete information. prior to intervention, a significant number of patients (18%) were not delivered to the next shift, most of which were in the night shift. the reason for missing those patients was that they were not present during the handover period because they had gone to the imaging or outpatient surgery units. after the educational program, with emphasis on the fact that all patients should be delivered even if they are temporarily not in the department (2), this rate reduced significantly and reached 6%. after the training, despite the implementation of checklist application, and contrary to our expectations, in the handover of 45% of patients, the checklist was not used, most of which were at night (only 34% of patients in night and 94% in day were handed over with checklist). residents declared that they did not use checklist due to the ed being crowded, especially at night. the increase in patient reception at night could be a challenge to providing care and continuity of patient information. moreover, when there is a heavy workload, abbreviations of verbal handover would result in inadequate communication and information oblivion (8). this study clearly demonstrated that the “who missed ip?” educational program and checklist improved not only the number of patients delivered, but also the quality of the transmission of information. our results are in agreement with reports that emphasized the positive effects of education (9) and the mnemonic checklist (8, 10, 11) on improvthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. shahrami et al. 4 ing the quality of the handovers. in this study, education and checklists were associated with proper information transfer (score higher than 9) rate improving from 25% to 94%, which indicates the impressive impact of the checklist on the quality of the handover. the handover duration is one the parameters that scholars are interested in shortening its value, along with increasing the quality of handover. a study that was conducted on nonsurgical patients in a specialist hospital showed that in the presence of a designed checklist, along with the increase in the quality, the duration of the handover was significantly reduced (a reduction of 22% from 99 ± 3.3 seconds to 77 ± 2.8 seconds per patient) (10). however, in our study, which was conducted on trauma patients, handover duration had increased significantly after education (from 73 ± 2.4 s to 96 ± 1.8 s per patient). this parameter was higher than the 73 to 92 seconds duration reported in ed (12), which could be due to the high information deficit before the intervention. on the other hand, the handover duration can also directly affect the content of the handover (13). therefore, the education and standard model increased the transmission of information and, as a result, increased the handover duration. in this study, to improve the efficiency of the handovers, the item “?” was designed to provide the opportunity of clarifying the ambiguous points by encouraging the receiving emergency residents to ask questions about handover (2). due to the timing of the night handover being at the peak of the trauma emergency, it is suggested to consider a scheduled shift overlap, so that the physicians handing over the patients have enough time to complete transfer of patient information (2). in addition, in order to improve the quality of the handover, it is recommended to train residents (for example, annually) about handover standards. also, the use of other handover methods, such as the electronic method, should be considered in order to maintain patient safety during this repeated and potentially risky process. suitable handover is not achieved by chance. it needs dedication of time, education, cooperation and alertness of all team members. we demonstrated that use of a mnemonic checklist and involvement of junior residents correlated with significant reduction in handover shortcomings. thus, the handover style should be specifically designed based on the requirements of specific units. 5. limitation this study was subject to limitations. the hawthorne effect could affect the post-intervention phase. 6. conclusion based on the findings of the present study, teaching handover standards and application of a handover checklist could be helpful in improving the quality of information delivery between emergency medicine residents and improve trauma patients’ handover indices. 7. appendix 7.1. acknowledgements this article is derivate from the masoomeh nazemi-rafi residency thesis to qualify in the emergency medicine specialty. 7.2. author contribution ◦ study conception and design: shahrami, hatamabadi, amini, nazemi-rafi ◦ acquisition of data: nazemi-rafi ◦ analysis and interpretation of data: nazemi-rafi ◦ drafting of manuscript: nazemi-rafi, shahrami ◦ critical revision: hatamabadi, amini authors’ orcids ali shahrami: 0000-0002-3001-6762 masoomeh nazemi-rafi: 0000-0003-4782-2901 hamidreza hatamabadi: 0000-0002-9085-8806 afshin amini: 0000-0001-8928-8212 7.3. funding/support none. 7.4. conflict of interest none. references 1. kauvar ds, wade ce. the epidemiology and modern management of traumatic hemorrhage: us and international perspectives. critical care. 2005;9(5):s1. 2. cheung ds, kelly jj, beach c, berkeley rp, bitterman ra, broida ri, et al. improving handoffs in the emergency department. annals of emergency medicine. 2010;55(2):171-80. 3. zakrison tl, rosenbloom b, mcfarlan a, jovicic a, soklaridis s, allen c, et al. lost information during the handover of critically injured trauma patients: a mixedmethods study. bmj qual saf. 2016;25(12):929-36. 4. kachalia a, gandhi tk, puopolo al, yoon c, thomas ej, griffey r, et al. missed and delayed diagnoses in the emergency department: a study of closed malpractice claims from 4 liability insurers. annals of emergency medicine. 2007;49(2):196-205. 5. gruen rl, jurkovich gj, mcintyre lk, foy hm, maier rv. patterns of errors contributing to trauma mortality: lessons learned from 2594 deaths. annals of surgery. 2006;244(3):371. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e7 6. patterson es, roth em, woods dd, chow r, gomes jo. handoff strategies in settings with high consequences for failure: lessons for health care operations. international journal for quality in health care. 2004;16(2):125-32. 7. solet dj, norvell jm, rutan gh, frankel rm. lost in translation: challenges and opportunities in physicianto-physician communication during patient handoffs. academic medicine. 2005;80(12):1094-9. 8. sujan m, spurgeon p. safety of patient handover in emergency care–results of a qualitative study. nutritional care of the patient with gastrointestinal disease. 2015:359. 9. ye k, mcd taylor d, knott jc, dent a, macbean ce. handover in the emergency department: deficiencies and adverse effects. emergency medicine australasia. 2007;19(5):433-41. 10. rudiger-sturchler m, keller di, bingisser r. emergency physician intershift handover–can a dinamo checklist speed it up and improve quality. swiss med wkly. 2010;140:w13085. 11. devlin mk, kozij nk, kiss a, richardson l, wong bm. morning handover of on-call issues: opportunities for improvement. jama internal medicine. 2014;174(9):1479-85. 12. mullan pc, macias cg, hsu d, alam s, patel b. a novel briefing checklist at shift handoff in an emergency department improves situational awareness and safety event identification. pediatric emergency care. 2015;31(4):231-8. 13. solet d, norvell j, rutan g, frankel r. physician-tophysician communication: methods, practice and misgivings with patient handoffs. journal of general internal medicine. 2004;19:108. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e37 https://doi.org/10.22037/aaem.v9i1.1187 or i g i n a l re s e a rc h comparing the accuracy of ohmann and alvarado scoring systems in detection of acute appendicitis; a crosssectional study seyed jalal eshagh hoseini1, mostafa vahedian2, alireza sharifi3∗ 1. department of surgery, school of medicine, shahid beheshti hospital, qom university of medical sciences, qom, iran. 2. research center for environmental pollutants, qom university of medical sciences, qom, iran. 3. student research committee, qom university of medical sciences, qom, iran. received: february 2021; accepted: april 2021; published online: 5 may 2021 abstract: introduction: alvarado scoring system (ass) and ohmann scoring system (oss) are two scoring systems for diagnosing acute appendicitis (aa). this study was designed to compare the diagnostic accuracy of the two mentioned scores in detection of acute abdominal cases at risk for aa. methods: in this prospective cross-sectional study, patients admitted to the emergency departments of two academic hospitals in qom, iran, with right lower quadrant (rlq) abdominal pain suspected to aa were evaluated. all cases were scored using ass and oss, and screening performance characteristics of the two scores were calculated and reported considering the pathologic findings as a gold standard. results: 174 patients with a preliminary aa diagnosis and the mean age of 38.1 ± 10.63 years (1173) were included in this study (62.07% male). at the optimal cutoff point of ≥7 for the ass, the sensitivity and the specificity were 46.43% (95% ci: 37.97%-55.07%), 97.05% (95% ci: 84.67%-92.93%), respectively. at the optimal cutoff point of ≥11 for the oss, the sensitivity and the specificity were 74.29% (95% ci: 66.22%-81.29%), and 55.88% (95% ci: 37.89% 72.82%), respectively. conclusion: based on the finding of this study, the ass ≥ 7 was more accurate than the oss ≥ 11 for detection of aa. but it should be considered that the overall accuracy of alvarado and ohmann scores in this regard were fair (0.83) and poor (0.67), respectively. keywords: appendicitis; decision support systems, clinical; data accuracy; comparative study cite this article as: eshagh hoseini s j, vahedian m, sharifi a. comparing the accuracy of ohmann and alvarado scoring systems in detection of acute appendicitis; a cross-sectional study. arch acad emerg med. 2021; 9(1): e37. 1. introduction the most common cause of acute abdominal pain is acute appendicitis (aa) with a lifetime risk of 7–8% (1, 2). it has dangerous complications such as perforation and peritonitis, which can be associated with morbidity and mortality (1). the incidence of aa is stable in most western countries, but recent studies show that aa is rapidly rising in newly industrialized countries (3). ghasemian m. et al. study, performed in 2019, reported that the annual incidence of aa in birjand (iran) was 12.74 per 10000 population (4). aa most often happens in individuals with the age of 10-30 years and it occurs in males and females with a ratio of approximately 1.4:1(5). ∗corresponding author: alireza sharifi; student research committee, qom university of medical sciences, qom, iran. email: habiball.al.sh@gmail.com, phone: +989106180377, orcid: https://orcid.org/0000-0002-6905-4539. although aa has a high incidence, its diagnosis can often be a challenge for physicians as the classic presentations of aa, such as periumbilical pain followed by vomiting, nausea and rovsing’s sign, happen in only 50-60% of cases (6). there is no single symptom, sign, or diagnostic tool to accurately confirm the diagnosis (7); therefore, the diagnosis of aa is based on a combination of history, physical examination, and laboratory findings, supplemented by selective focus imaging (8). imaging modalities such as radiography, ultrasound, ct scan, and mri are used to diagnose aa (9, 10) but there is major controversy over their diagnostic role (8). in an attempt to improve the accuracy of aa diagnosis, several scoring systems such as alvarado scoring system (ass) and ohmann scoring system (oss) have been developed to systematically combine laboratory values, physical exam findings, symptoms and patient characteristics (6). ass was first introduced in 1986. it is the most reported scoring system for evaluating the aa (6). another common scorthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s j. eshagh hoseini and et al. 2 ing system is oss that includes seven clinical parameters and a white blood cell (wbc) count (11). different studies report different diagnostic accuracies for these scoring systems, for example, yilmaz et al. study in 2017 (12) reported that ass and oss can be useful for predicting aa, but arzu sencan et al. study in 2014 (13) stated that their specificity and sensitivity were not sufficient for diagnosing aa. although ass and oss are inexpensive, easy to use and reproducible with high success rates, they still have not become the main part of routine practice (14). so, this study was designed to compare the diagnostic accuracy of alvarado and ohmann scores in detection of acute abdominal cases in favor of aa. 2. methods 2.1. study design and setting in this prospective cross-sectional study, patients who were admitted to the emergency department of nekuee and shahid beheshti hospitals, qom, iran, with right lower quadrant (rlq) abdominal pain suspected to aa, during one year, were evaluated. this study was approved by the ethics committee of qom university of medical sciences (ethics code: d/24/350). all subjects consented to participate in the study, and the data were recorded by emergency department (ed) physicians. 2.2. participants all patients above 11 years old with rlq abdominal pain suspected to aa and candidate for appendectomy, who were referred to ed during the study period, were included using non-probability sampling method. the exclusion criteria were as follows: (a) being under 11 years of age, (b) elective appendectomy, (c) pregnancy, (d) phlegmon formation, (e) existence of abdominopelvic malignancy. 2.3. data gathering the following data were recorded for all subjects: complaints at the time of admission, physical examination, and laboratory findings. the obtained data were used to calculate alvarado and ohmann scores by a surgeon before appendectomy. the parameters of ass and oss are demonstrated in appendix 1. all patients underwent appendectomy and were categorized into two groups according to histopathologic diagnosis: positive appendectomy (pa) and negative appendectomy (na). ass evaluates 8 parameters, which include symptoms, clinical findings, and leukocyte count. the highest possible score is 10, and our optimal cutoff point for appendectomy was ≥ 7. oss is also composed of 8 parameters (tenderness in right lower quadrant, rebound tenderness, presence of urinary system complaint, character of pain, re-localization of pain to the right lower quadrant, age, leukocyte count, and abdominal rigidity). the highest possible score is 16, and we recommended appendectomy for scores ≥ 11. 2.4. statistical analysis the data were analyzed using spss version 22.0. descriptive statistics for categorical data were expressed as numbers and percentages and median (minimum-maximum) were used to express continuous data based on normal distribution. student’s t-test was used for variables with normal distribution. the screening performance characteristics of the scoring systems were measured. a greater area under the receiver operating characteristic (roc) curve (auc) indicates better diagnostic value. p<0.05 was considered statistically significant. sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ration (plr) and negative likelihood ration (nlr), and accuracy with 95% confidence interval were calculated and compare between two scoring systems. in the present study, area under the curve of 90 to 100 was considered as excellent accuracy, 80 to 90 as good, 70 to 80 as fair, 60 to 70 as poor, and 50 to 60 as fail. 3. results 3.1. baseline characteristics of studied cases appendectomy was performed for 181 patients with suspicion to aa but after histopathology consideration, 7 patients were excluded because they had tumoral appendicitis. therefore, 174 patients with a preliminary aa diagnosis and the mean age of 38.1 ± 10.63 years (1173) were included in this study (62.07% male). table 1 shows the baseline characteristics of studied cases. the diagnosis of aa was histopathologically confirmed in 136 cases (78.16%) and 38 (21.84%) patients had negative appendectomy. 3.2. comparing the scores the median ass and oss scores were 7 (2 10) and 14 (3 16), respectively. screening performance characteristics of the studied systems in determining the cases with aa are presented in table 2 and figure 1. sensitivity and specificity of oss in the cut-off value of ≥11 were 74.29% (95% ci: 66.22 81.29), and 55.88% (95% ci: 37.89 72.82), respectively. for ass, these measures were 46.43% (95% ci: 37.97 55.07) and 97.05% (95% ci: 84.67 92.93), respectively. area under the roc curves of ass and oss in detection of aa cases were 0.83 (95% ci: 0.770.88) and 0.67 (95% ci: 0.598 to 0.742), respectively (p = 0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e37 4. discussion in our study, oss’s (cut off point ≥11) sensitivity, specificity, and ppv and npv were 74.29%, 55.88%, 87.4%, and 34.5%, respectively. also, ass’s (cut off point ≥7) sensitivity, specificity, and ppv and npv were 46.43%, 97.6%, 98.5%, and 30.6%, respectively. based on the results of the current study, oss has higher sensitivity and npv than alvarado scoring system in diagnosis of aa, but alvarado score has higher specificity and ppv than ohmann score. aa is the most common reason for abdominal pain in cases seen in surgery clinics and emergency services but its definitive diagnosis can be difficult. delayed diagnosis and intervention in patients with aa can lead to high-risk complications such as perforation, sepsis, and morbidity and mortality (12). appendectomy is performed in 12 to 23% of all people during their lifetime (15). on the other hand, the rate of unnecessary negative appendectomy based on the intraoperative and histopathological results is high (about 12% -40%). however, there are now many diagnostic scoring systems such as ass and oss, as well as advanced imaging methods to decrease the rate of negative appendectomies (12). in chong cf et al. study, ass has been reported to be less specific in asian populations compared to american/european populations (7). the present study was designed to compare the ability of ass and oss in predicting aa. ass is thought to have high sensitivity and specificity (12). many studies have been done affirming validity for predicting aa. for example, in schneider et al. study (16), alvarado score ≥7 had sensitivity and specificity of 72% and 82%, respectively. in another study conducted by hamid kariman et al. (17), alvarado score greater than 7 yielded 37% sensitivity and 95.65% specificity. the sensitivity and specificity of ass in our study were higher than those reported in kariman and schneider studies. oss is an easy and useful system employed in diagnosis of aa (18). hassan erdem et al. study (19) reported sensitivity, specificity, ppv and npv of oss (cutoff point = 12) as 96%, 42%, 78% and 83%, respectively. in another study by sanjay n koppad et al. (11) the sensitivity, specificity, ppv, and npv of oss (cutoff point = 12) were 96%, 66.7%, 82.8, and 90.9%, respectively. the reported ppv in our study was higher than these studies. some studies have compared ass and oss in diagnosis of aa. in korkut et al. study in 2020 (14), 74 patients were categorized into two groups according to their histopathological results: positive and negative appendectomy. the accuracy of different scoring systems in diagnosis of the aa was investigated. sensitivity, specificity, ppv and npv were 71.9%, 89.9%, 97.92%, 30.77%, respectively, for oss; versus 60.9%, 89.9%, 97.56% and 24.24%, respectively, for ass. their study reported a higher accuracy rate for oss. in another study done by yilmaz et al.(12), a total of 105 patients diagnosed with aa were enrolled, then oss and ass scores were calculated, separately. they concluded that ass can predict aa better than oss, while oss was more useful for providing guidance in diagnosing aa when conditions are more obscured and uncertain. in a review study conducted by daniel lh et al. in 2017, the classical picture of shifting pain associated with nausea, vomiting, and anorexia happens in less than half of presentations (20), while in our study, shifting pain, vomiting, and loss of appetite percentile is reported in 73.61% (n=106), 59.19% (n=103) and 70.68% (n=123) of cases, respectively. abdominal pain has been introduced as the most common manifestation (21), which is in line within our study result (89.65% (n=156)). based on our study results, the most common symptoms and signs were rlq pain (n=156), rlq tenderness (n=151), and loss of appetite (n=123), respectively. there is not any specific bloods test for aa. however, if there is an increased wbc, c reactive protein (crp), proportion of polymorphonuclear (pmn) cells, or granulocyte count, then aa is more likely (21); while leukocytosis is reported in 71.26%(n=124) of the cases in our study. considering the fair and poor accuracy of studied scoring systems, it seems that ass and oss need further modifications to be more accurate than what they are now to be applicable in routine practice. 5. limitations the small sample size and intrinsic shortcomings of crosssectional studies were among the most important limitations of the present study. 6. conclusion based on the finding of this study, ass ≥ 7 was more accurate than the oss ≥ 11 for detection of aa. but it should be considered that the overall accuracy of alvarado and ohmann scores in detection of aa were fair and poor, respectively. 7. declarations 7.1. author contribution study concept and design and analysis and interpretation of data: s.j.e.h.; drafting of the manuscript: a.sh.; statistical analysis and interpretation of data m.v.; critical revision of the manuscript for important intellectual content: a.sh. 7.2. ethical approval ethics committee approval was received for this study from qom university of medical sciences. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s j. eshagh hoseini and et al. 4 7.3. funding/support we did not receive any funding and support for this study. 7.4. conflict of interest there is no conflict of interest for authors. references 1. addiss dg, shaffer n, fowler bs, tauxe rv. the epidemiology of appendicitis and appendectomy in the united states. american journal of epidemiology. 1990;132(5):910-25. 2. sartelli m, baiocchi gl, di saverio s, ferrara f, labricciosa fm, ansaloni l, et al. prospective observational study on acute appendicitis worldwide (posaw ). world journal of emergency surgery. 2018;13(1):1-10. 3. ferris m, quan s, kaplan bs, molodecky n, ball cg, chernoff gw, et al. the global incidence of appendicitis: a systematic review of population-based studies. annals of surgery. 2017;266(2):237-41. 4. ghasemian moghaddam mr, hassanzadeh-taheri m, hosseini m, salimi m, hassanzadeh-taheri m. epidemiological aspects of patients underwent appendectomy in birjand, iran, from may 2017 to 2019. journal of surgery and trauma. 2019;7(3):91-7. 5. di saverio s, birindelli a, kelly md, catena f, weber dg, sartelli m, et al. wses jerusalem guidelines for diagnosis and treatment of acute appendicitis. world journal of emergency surgery. 2016;11(1):1-25. 6. golden sk, harringa jb, pickhardt pj, ebinger a, svenson je, zhao y-q, et al. prospective evaluation of the ability of clinical scoring systems and physician-determined likelihood of appendicitis to obviate the need for ct. emergency medicine journal. 2016;33(7):458-64. 7. agarwal r, agarwal a, kumar a, kumar m. the validity and utility of combining ultrasonography with different clinical scores in diagnosis of acute appendicitis. international surgery journal. 2019;6(4):1084-92. 8. varadhan kk, neal kr, lobo dn. safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: metaanalysis of randomised controlled trials. bmj. 2012;344. 9. ceylan b, aslan t, çınar a, kurt ar, akkoyunlu y. can platelet indices be used as predictors of complication in subjects with appendicitis? wiener klinische wochenschrift. 2016;128(8):620-5. 10. raptis da, eshmuminov d, tschuor c, limani p, neff t, reding t, et al. diagnostic value of pancreatic stone protein in comparison to white cell count and c reactive protein in the diagnosis of acute appendicitis a prospective multicenterdiagnostic accuracy trial. journal of surgery. 2019. 11. koppad sn, vandakudri ab, desai m, kodliwadmath h. evaluation of ohmann score and correlation with ultrasound for diagnosing acute appendicitis. int j orthopaed traumatol surg sci. 2016;2(1):234-8. 12. yılmaz em, kapçı m, çelik s, manoğlu b, avcil m, karacan e. should alvarado and ohmann scores be real indicators for diagnosis of appendicitis and severity of inflammation? turkish journal of trauma and emergency surgery. 2017;23(1):29-33. 13. sencan a, aksoy n, yıldız m, okur ö, demircan y, karaca i̇. the evaluation of the validity of alvarado, eskelinen, lintula and ohmann scoring systems in diagnosing acute appendicitis in children. pediatric surgery international. 2014;30(3):317-21. 14. korkut m, bedel c, karancı y, avcı a, duyan m. accuracy of alvarado, eskelinen, ohmann, ripasa and tzanakis scores in diagnosis of acute appendicitis; a cross-sectional study. archives of academic emergency medicine. 2020;8(1). 15. davis gn, swaminathan m. acute appendicitis-new diagnostic algorithm using ripasa score and non-contrast computeed tomography scan. jpma j pak med assoc. 2019;69(1ŝ1). 16. schneider c, kharbanda a, bachur r. evaluating appendicitis scoring systems using a prospective pediatric cohort. annals of emergency medicine. 2007;49(6):778-84. e1. 17. kariman h, shojaee m, sabzghabaei a, khatamian r, derakhshanfar h, hatamabadi h. evaluation of the alvarado score in acute abdominal pain. ulus travma acil cerrahi derg. 2014;20(2):86-90. 18. kiyak g, korukluoğlu b, ozgün y, devay ao, kuşdemir a. evaluation of ohmann and eskelinen scores, leukocyte count and ultrasonography findings for diagnosis of appendicitis. ulusal travma ve acil cerrahi dergisi= turkish journal of trauma & emergency surgery: tjtes. 2009;15(1):77-81. 19. erdem h, çetinkünar s, daş k, reyhan e, değer c, aziret m, et al. alvarado, eskelinen, ohhmann and raja isteri pengiran anak saleha appendicitis scores for diagnosis of acute appendicitis. world journal of gastroenterology: wjg. 2013;19(47):9057. 20. baird dl, simillis c, kontovounisios c, rasheed s, tekkis pp. acute appendicitis. bmj. 2017;357. 21. humes d, simpson j. acute appendicitis. bmj. 2006;333(7567):530-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e37 figure 1: the area under the receiver operating characteristic (roc) curves of alvarado and ohmann scoring systems (p = 0.001). appendix 1: parameters of alvarado and ohmann scoring systems alvarado parameters score ohmann parameters score migration rlq pain 1 tenderness in rlq 4.5 anorexia 1 rebound tenderness 2.5 nausea and vomiting 1 absence of urinary complications 2 rlq tenderness 2 steady pain 2 rebound tenderness 1 white blood cell count >10000/cm3 1.5 fever (>37.3) 1 age <50 years 1.5 leukocytosis 2 migration rlq pain 1 shift to the left of neutrophils 1 rigidity 1 total 10 total 16 rlq: right lower quadrant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s j. eshagh hoseini and et al. 6 table 1: baseline characteristics of studied patients variables values (n= 174) age (years) mean ± sd 38.1 ± 10.63 gender male 108 (62.07) female 66 (37.93) appendectomy findings positive 136 (78.16) negative 38 (21.84) scoring systems parameters rlq tenderness 156 (89.66) migrating rlq pain 10 (60.92) anorexia 12 (70.69) nausea and vomiting 103 (59.2) shift to the left of neutrophils 85 (48.85) rebound tenderness 11 (64.37) rigidity 54 (31.03) fever (>37.3) 62 (35.63) leukocytosis 124 (71.26) negative urine complications 142 (81.61) steady pain 120 (68.97) age< 50 year 151 (86.78) data are presented as mean ± standard deviation (sd) or frequency (%). rlq: right lower quadrant. table 2: screening performance characteristics of alvarado and ohmann scoring systems in prediction of acute appendicitis in emergency department character alvarado (≥ 7) ohmann (≥ 11) true positive 65 104 false positive 1 15 true negative 33 19 false negative 75 36 sensitivity 46.43 (37.97 55.07) 74.29 (66.22 81.29) specificity 97.05 (84.67 92.93) 55.88 (37.89 72.82) positive predictive value 98.5 (90.34 99.78) 87.4 (82.43 91.11) negative predictive value 30.6 (27.17 34.16) 34.5 (25.93-44.31) positive likelihood ratio 15.77 (2.27-109.76) 1.68 (1.14 2.50) negetive likelihood ratio 0.55 (0.47 0.65) 0.46 (0.31 0.69) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e26 or i g i n a l re s e a rc h potential impact of 3% hypertonic saline infusion on tramadol poisoning-induced electrocardiogram changes; a randomized clinical trial ali omraninava1, ahmad mehdizade1, ebrahim karimi1∗, amir ghabousian2 1. emergency department, besat hospital, aja university of medical sciences, tehran, iran. 2. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. received: february 2022; accepted: march 2022; published online: 13 april 2022 abstract: introduction: tramadol is a synthetic analgesic with weak mu-opioid receptor agonist activity. tramadol overdose is associated with adverse cardiac effects due to inhibiting cardiac na+ and k+ channels. this study aimed to investigate the potential ameliorative role of 3% hypertonic saline on the electrocardiogram (ecg) changes in patients presenting with tramadol poisoning. methods: this was a single-center, controlled, randomized, single-blind clinical trial. patients were randomized into the case (received hypertonic saline) and control (received placebo) groups. ecg was obtained twice in each group (upon arrival and following the intervention). response to therapeutic interventions was evaluated using wilcoxon signed ranks test. results: a total of 76 patients were included. the mean age of patients was 24.88 ± 4.29 years, and 62 (81.6%) were male. the mean ingested dose of tramadol was 1673.68 ± 608.85 (range: 550-2750) mg. the number needed to treat and the absolute risk reduction of 3% hypertonic saline in the treatment of wide qrs were 1 (95% ci: 1.00 – 1.00) and 100%, respectively. in the treatment of long qtc, these measures were 1.9 (95%ci: 1.2 – 4.5) and 53.85% (95%ci: 22.00 – 85.69), respectively. conclusion: given that hypertonic saline infusion can significantly ameliorate tramadol-mediated ecg changes, including qrs prolongation and qt lengthening, it can be regarded as a potential therapeutic strategy to prevent the development of life-threatening ventricular arrhythmias caused by tramadol toxicity. keywords: poisoning; tramadol; saline solution; infusions, intravenous cite this article as: omraninava a, mehdizade a, karimi e, ghabousian a. potential impact of 3% hypertonic saline infusion on tramadol poisoning-induced electrocardiogram changes; a randomized clinical trial. arch acad emerg med. 2022; 10(1): e26. https://doi.org/10.22037/aaem.v10i1.1567. 1. introduction tramadol is a synthetic analgesic with weak mu-opioid receptor agonist activity and is commonly used to mitigate moderate to severe pain (1). it is well-established that tramadol hinders the reuptake of several neurotransmitters, including serotonin and norepinephrine (2). even though tramadol has illustrated a low risk for dependence and abuse compared to other opioids, the incidence of tramadolmediated toxicity and its complications have been on the rise over the past decades (3). tramadol poisoning can ad∗corresponding author: ebrahim karimi; emergency department, besat hospital, afsariyeh avenue, basij highway, tehran iran. tel: +989124544838, email: ebrahimkarimi86@gmail.com, orcid: http://orcid.org/0000-00023542-9099. versely affect multiple organs throughout the body. one of the most fearsome ramifications of tramadol toxicity is its catastrophic impact upon cardiac action potential (4). according to the available studies, at high doses, tramadol can interfere with cardio-myocyte depolarization and repolarization via inhibiting voltage-gated na+ and delayed rectifier k+ channels, respectively (5). electrocardiogram (ecg) findings in patients with tramadol poisoning are mainly consistent with the na+ channel blockade activity (6). the mainstay of tramadol toxicity treatment is general supportive care and possible seizure management (7). however, there is a lack of evidence with regard to reversing potentially life-threatening ecg changes in this regard. the use of hypertonic saline (hs) with the aim of sodium loading has been identified as a potential alternative method to sodium bicarbonate use in patients with tricyclic antidepressants this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. omraninava et al. 2 (tca) intoxication, which also associates with na+ channel blockade (8). however, the impact of hypertonic saline on tramadol-induced ecg abnormalities has never been studied. this study aimed to investigate the potential impact of 3% hs on the ecg changes and associated complications in patients presenting with tramadol poisoning. 2. methods 2.1. study design and setting this is a controlled, randomized, single-blind clinical trial intending to evaluate the potential therapeutic role of 3% hs in ameliorating ecg changes and associated complications followed by tramadol toxicity. the study was conducted on patients presenting to besat general hospital, tehran, iran, from march through october 2021. the local ethics committee (biomedical research ethics committee) approved the protocol of present study (ir.ajaums.rec.1400.126) and it was registered in iranian registry of clinical trials (irct: 20220213054017n1) written informed consent was obtained from patients or their next of kin and researchers acted solely based on the helsinki declaration. 2.2. participants tramadol poisoned cases with at least one of the following ecg abnormalities were included: right bundle brunch block (rbbb), long qtc, tall r wave, prolonged qrs interval, and right axis deviation. these parameters were selected based on the available data regarding the ecg manifestations of na+ and k+ channel blockers (9, 10). patients not willing to participate, those under 18 years of age, pregnant women, and patients with underlying cardiovascular disorders, including heart failure and cardiomyopathy, patients on antiarrhythmic or arrhythmogenic drugs, and those with liver failure, electrolyte disturbance (hypoand hypernatremia), and chronic kidney disease, were excluded from the present study (figure 1). 2.3. data gathering and therapeutic intervention the demographic characteristics (age and sex), medical history, physical findings upon arrival, drug dosage, and relevant complications (seizure, falling, shoulder dislocation, head trauma, and loss of consciousness) were gathered using a predesigned checklist. eligible patients were randomly allocated to either case (intervention) or control (placebo) group using a simple randomization method. all patients were treated according to the current standard of care for acute tramadol poisoning. patients in the control group, received 3 ml/kg (maximum dose:150 ml) of 3% dextrose water over 20 minutes as a placebo. however, patients in the intervention group received the intravascular infusion of 3% hypertonic saline (3 ml/kg over 20 minutes; maximum dose: 150 ml) in addition to the standard of care. ecg was obtained twice in each group (upon arrival and after completing the intervention). a 12-lead ecg was acquired by a registered nurse under the supervision of a senior emergency medicine resident using a carewell digital 12-channel ecg1112m electrocardiograph. the interpretation of ecg was carried out by a cardiologist blinded to the study protocol. to this end, heart rate, qrs axis (normal between -30 to +100), qrs duration (normal< 110 ms), qtc interval (normal<0.44 ms), bundle branch block, and the presence of dominant r wave in avr (r wave height greater than 3 mm or r/s ratio more than 0.7) were documented. right bundle branch block (rbbb), long qtc, tall r wave, wide qrs, and axis deviation were the studied ecg abnormalities. 2.4. outcomes the primary outcome of the current study was the effects of 3% hs on ecg changes and the secondary outcome was its effect on other complications of tramadol poisoning. 2.5. statistical analysis the study analyses were performed using ibm®spss®statistics 26. normal distribution was assessed using kolmogorov-smirnov method. data were presented as mean ± standard deviation or frequency (%). taking into account normality, we used independent-samples t-test and mann-whitney u test to compare quantitative characteristics between the two groups, while we employed chi-square test for qualitative ones. response to therapeutic intervention was evaluated using wilcoxon signed ranks test. in any case, we considered p-value less than 0.05 as significant. 3. results 3.1. baseline characteristics of studied cases a total of 76 patients with tramadol intoxication and ecg abnormality were enrolled during this clinical trial and were included in final analysis. the mean age of patients was 24.88 ± 4.29 years, and 62 (81.6%) were male. the mean ingested dose of tramadol was 1673.68 ± 608.85 (range: 5502750) mg. aspiration pneumonia was detected in 2 (2.6%) patients, signs of head trauma in 1 (1.3%), altered mental status upon arrival in 31 (32.3%), seizure in 37 (38.5%), and shoulder dislocation in 25 (32.9%). there was no statistically significant relationship between tramadol dosage and seizure occurrence (1657.14 ± 654.29 mg in patients who developed seizure and 1683.33 ± 587.66 mg in those who did not, p= 0.858). out of 76 patients, 1 (1.3%) patient died despite resuscitation efforts. this patient had been randomly allocated to the control group. the intervention and control groups were this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e26 table 1: comparison of baseline and post-intervention electrocardiogram (ecg) findings between case (3% hypertonic saline) and control (placebo) groups ecg findings case (n=40) control (n=36) p-value baseline rbbb 3 (7.5) 6 (16.7) 0.217 wide qrs 5 (12.5) 6 (16.7) 0.606 long qtc 13 (32.5) 13 (36.1) 1.00 tall r wave 14 (35.0) 14 (38.9) 1.00 axis deviation 17 (42.5) 16 (44.4) 0.864 post-intervention rbbb 1 (2.5) 3 (8.3) 0.255 wide qrs 0 (0) 6 (16.7) 0.007 long qtc 4 (10.0) 11 (30.6) 0.025 tall r wave 9 (22.5) 10 (27.8) 0.596 axis deviation 11 (27.5) 9 (25.0) 0.805 data are presented as number (%).; rbbb: right bundle branch block. figure 1: flow diagram of patient allocation. ecg: electrocardiogram. similar regarding the mean age (24.53 ± 4.03 vs. 25.28 ± 4.58, respectively; p = 0.449), male/female ratio (33/7 vs. 29/7; respectively; p = 0.827), and ingested tramadol dose (1548.75 ± 635.43 vs. 1812.50 ± 553.86; respectively; p = 0.059). 3.2. ecg features table 1 summarizes abnormal ecg findings upon arrival and after intervention in both study groups. the two groups had similar frequency of rbbb (p = 0.217), long qtc (p = 1.00), this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. omraninava et al. 4 tall r wave (p = 1.00), wide qrs (p = 606), and axis deviation (p = 0.864) in baseline ecg, while the frequency of wide qrs interval (p = 0.007) and long qtc (p = 0.025) was significantly lower in patients who received 3% hypertonic saline in the second ecg (table 1). the number needed to treat and the absolute risk reduction of 3% hypertonic saline in the treatment of wide qrs were 1 (95% ci: 1.00 – 1.00) and 100%, respectively. in the treatment of long qtc, these measures were 1.9 (95%ci: 1.2 – 4.5) and 53.85% (95%ci: 22.00 – 85.69), respectively. 4. discussion based on the results of this clinical trial, 3% hypertonic saline administration in addition to the routine standard of care in patients with tramadol poisoning can ameliorate potentially life-threatening ecg changes, including qrs prolongation and qtc lengthening. routine standard of care itself cannot result in statistically significant changes in the aforementioned parameters. it is noteworthy that after receiving hypertonic saline, the absolute risk reduction for qrs prolongation and qtc interval was 100% and 53.85%, respectively. this gap between the absolute risk reduction for qrs and qt interval, in part, is due to the fact that tramadol-induced cardiotoxicity is a combination of na+ and k+ channels blockade. the qrs duration stands for the ventricular depolarization time and qtc interval mainly represents ventricular repolarization. however, given that qt interval comprises qrs complex, st segment, and t wave, a widened qrs duration can give rise to qt prolongation without inducing any repolarization delay (11). an acquired prolonged qtc interval, which mostly occurs owing to the inhibition of the inward potassium rectifier (ikr) channels, is associated with a high risk of developing life-threatening arrhythmias, such as torsades de points (tdp)(12). currently, magnesium sulfate is used for treating and preventing the recurrence of tdp. on the other hand, a widened qrs duration due to inhibition of na+ channels, can also increase the possibility of developing ventricular arrhythmia (10, 13). although the pros and cons of hypertonic saline administration in the setting of tramadol poisoning have not already been explored, its ameliorative role has been proven to be equal or superior to sodium bicarbonate in animals with tca toxicity, which also leads to na+ channel blockade (14, 15). moreover, in our study, the administration of hypertonic saline did not contribute to any significant adverse effect. at present, the drug enforcement administration has placed tramadol into schedule iv of controlled substances, implying that it contains a low risk for dependence and abuse. however, opioid poisoning and abuse are not thin on the ground, particularly when it comes to the middle east (16, 17). published studies have demonstrated conflicting results regarding dose-dependency of seizure in patients with tramadol poisoning. a recent meta-analysis, in which 51 studies were included, has found that among patients presenting with tramadol overdose, not taking tramadol abusers into account, the drug dose was not significantly different among patients with or without seizure development (pooled standardized mean difference: 0.27, ci 95%:0.15 to 0.7) (18). these findings were consistent with the current study results, which included patients with tramadol overdose. in harmony with our results, in a prospective study conducted on 1402 patients with tramadol poisoning, the most frequent abnormal ecg findings were sinus tachycardia (33%), qrs right axis deviation (24.2%), qrs widening (6.5%), long qtc interval (18.4%), and rbbb (5.2%) (19). nonetheless, the management of cardiotoxicity induced by tramadol is complex, given the involvement of both na+ and k+ channels. furthermore, there is no consensus regarding the best approach to manage this condition. our study shows that hypertonic saline infusion is an effective therapeutic strategy to mitigate tramadol-mediated ecg abnormalities. lastly, our study had several limitations. it was carried out in a single center setting and included a limited number of patients. further multicenter studies are necessary to prove the generalizability of these findings. 5. conclusion given that hypertonic saline infusion can significantly ameliorate tramadol-mediated ecg changes, including qrs prolongation and qt lengthening, it can be regarded as a potential therapeutic strategy to prevent the development of ventricular arrhythmias caused by tramadol toxicity. 6. declarations 6.1. acknowledgments none. 6.2. authors’ contributions all the authors meet the standard authorship criteria based on the recommendations of international committee of medical journal editors. 6.3. funding none. 6.4. conflict of interest none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e26 references 1. bakr mh, radwan e, shaltout as, farrag aa, mahmoud ar, abd-elhamid th, et al. chronic exposure to tramadol induces cardiac inflammation and endothelial dysfunction in mice. sci rep. 2021;11(1):18772. 2. grond s, sablotzki a. clinical pharmacology of tramadol. clin pharmacokinet. 2004;43(13):879-923. 3. beakley bd, kaye am, kaye ad. tramadol, pharmacology, side effects, and serotonin syndrome: a review. pain physician. 2015;18(4):395-400. 4. hafezi moghadam p, zarei n, farsi d, abbasi s, mofidi m, rezai m, et al. electrocardiographic changes in patients with tramadol-induced idiosyncratic seizures. turk j emerg med. 2016;16(4):151-4. 5. mert t, gunes y, guven m, gunay i, gocmen c. differential effects of lidocaine and tramadol on modified nerve impulse by 4-aminopyridine in rats. pharmacology. 2003;69(2):68-73. 6. emamhadi m, sanaei-zadeh h, nikniya m, zamani n, dart rc. electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. am j emerg med. 2012;30(8):14815. 7. nakhaee s, hoyte c, dart rc, askari m, lamarine rj, mehrpour o. a review on tramadol toxicity: mechanism of action, clinical presentation, and treatment. forensic toxicol. 2021;39(2):293-310. 8. eken c. hypertonic saline: an alternative therapy in tca overdoses failed to respond sodium bicarbonate. clin toxicol (phila). 2008;46(5):488. 9. niemann jt, bessen ha, rothstein rj, laks mm. electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. am j cardiol. 1986;57(13):1154-9. 10. delk c, holstege cp, brady wj. electrocardiographic abnormalities associated with poisoning. am j emerg med. 2007;25(6):672-87. 11. shahsavarinia k, ghojazadeh m, ghabousian a, hatefnia f, soleimanpour m, soleimanpour h. an umbrella review of clinical efficacy and adverse cardiac events associated with hydroxychloroquine or chloroquine with or without azithromycin in patients with covid-19. anesth pain med. 2021;11(4):e115827. 12. ghabousian a, alizadehasl a, ansari n, haghazali m. the potential ameliorating role of spironolactone in trastuzumab mediated cardiotoxicity: a narrative review. int j med toxicol forensic med. 2021:36127. 13. wellens hjj. ventricular tachycardia: diagnosis of broad qrs complex tachycardia. heart. 2001;86(5):579. 14. paksu ms, zengin h, ilkaya f, paksu s, guzel h, ucar d, et al. can empirical hypertonic saline or sodium bicarbonate treatment prevent the development of cardiotoxicity during serious amitriptyline poisoning? experimental research. cardiovasc j afr. 2015;26(3):134-9. 15. mccabe jl, cobaugh dj, menegazzi jj, fata j. experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. ann emerg med. 1998;32(3 pt 1):329-33. 16. alavi-moghaddam m, parsa-mahjoub m, ghodssighassemabadi r, bitazar b. association of admission blood glucose level with major adverse cardiac events in acute coronary syndrome; a cohort study. arch acad emerg med. 2019;7(1):e26. 17. dehghani k, shojaie m, pourdavood ah, khajouei m. stress cardiomyopathy (takotsubo syndrome) following accidental methadone poisoning; report of two pediatric cases. arch acad emerg med. 2019;7(1):e22. 18. nakhaee s, amirabadizadeh a, brent j, miri-moghaddam e, foadoddini m, farrokhfall k, et al. tramadol and the occurrence of seizures: a systematic review and metaanalysis. crit rev toxicol. 2019;49(8):710-23. 19. alizadeh ghamsari a, dadpour b, najari f. frequency of electrocardiographic abnormalities in tramadol poisoned patients; a brief report. emerg (tehran). 2016;4(3):151-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e34 https://doi.org/10.22037/aaem.v9i1.1210 or i g i n a l re s e a rc h neurological manifestations and their correlated factors in covid-19 patients; a cross-sectional study farzad ashrafi1, davood ommi1, alireza zali1, sina khani2, amirali soheili2, mehran arab-ahmadi3, behdad behnam4, shabnam nohesara5∗, farbod semnani6, alireza fatemi7, mehri salari1, reza jalili khoshnood1, mohammad vahidi2, niloofar ayoobi-yazdi3, saeed hosseini toudeshki8, elham sobhrakhshankhah4 1. functional neurosurgery research center, shohadaye tajrish neurosurgical center of excellence, shahid beheshti university of medical sciences, tehran, iran. 2. student research committee, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. advanced diagnostic and interventional radiology research center, tehran university of medical sciences, tehran, iran. 4. department of internal medicine, iran university of medical sciences, tehran, iran. 5. mental health research center, iran university of medical sciences, tehran, iran. 6. students’ scientific research center, tehran university of medical sciences, tehran, iran. 7. department of infectious diseases, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 8. department of radiation oncology, iran university of medical sciences, tehran, iran. received: february 2021; accepted: february 2021; published online: 27 april 2021 abstract: introduction: covid-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. this study aimed to evaluate the neurologic manifestations and their correlated factors in covid-19 patients. methods: this retrospective observational study was conducted from march 17, 2020 to june 20, 2020 in a tertiary hospital in iran. the study population consisted of adult patients with a positive result for covid-19 real-time reverse transcriptase polymerase chain reaction (rt-pcr) using nasopharyngeal swabs. both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. results: 727 covid-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). at least one neurological symptom was observed in 403 (55.4%) cases. headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (bmi) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to covid-19 patients without neurological symptoms. o2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). in addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (nlr) (p = 0.02) and c-reactive protein (crp) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. conclusion: the prevalence of neurological manifestations in the studied cases was high (55.4%). this prevalence was significantly higher in older age, grated bmi, longer lasting disease, and opium usage. keywords: covid-19; neurologic manifestations; blood cell count; risk factors cite this article as: ashrafi f, ommi d, zali a, khani s, soheili a, arab-ahmadi m, behnam b, nohesara s, semnani f, fatemi a, salari m, jalili khoshnood r, vahidi m, ayoobi-yazdi n. neurological manifestations and their correlated factors in covid-19 patients; a cross-sectional study. arch acad emerg med. 2021; 9(1): e34. ∗corresponding author: mental health research center, first floor, tehran psychiatry institute, shahid mansouri alley, niayesh avenue, sattarkhan street, tehran, iran. tel: +989122899816, fax: +98.2122701022, email: shnohesara@gmail.com, orcid: https://orcid.org/0000-0003-4944-7033. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. ashrafi and et al. 2 1. introduction several studies showed clinical characteristics of the “coronavirus disease 2019 (covid-19)” disease. in a systematic review by leiwen fu et al., fever (83.3%) cough (60.3%) and fatigue (38.0%) were the most common clinical symptoms (1). respiratory tract infections and pneumonia have been commonly observed in infected patients. however, in some occasions, they show neurological alterations and signs including seizure, status epilepticus, impairment of consciousness, and encephalopathies (2). besides, a study reported that some patients without typical symptoms of covid-19 including fever, cough, anorexia, and diarrhea presented neurological manifestations as the initial symptoms such as dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure (3). these neurological symptoms were also seen in sars-cov infection, which caused polyneuropathy, encephalitis, and ischemic stroke and in mers-cov infection, which caused disturbance of consciousness, paralysis, ischemic stroke, guillainbarre syndrome, and seizure (4). although there is no unanimity regarding the underlying mechanisms, it is probably due to exaggerated cytokine responses and/or the subsequent hypercoagulopathy in vessels, which cause anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizure (5). due to lack of comprehensive and sufficient evidence concerning covid19 and its neurological manifestations, hereby, we report the characteristic neurological manifestations of sars-cov-2 infection in patients with a laboratory-confirmed diagnosis of covid-19 and investigate the association between neurological symptoms and baseline characteristics as well as laboratory findings. 2. methods 2.1. study design and setting this retrospective observational study was conducted in shohadaye tajrish hospital, a tertiary academic hospital located in tehran, iran. this hospital is among the major designated centers for covid-19 patients during the pandemic. from march, 17, 2020 to june 20, 2020 all suspected individuals aged >18 years presenting with typical covid19 symptoms were tested for covid-19 using a throat swab. then, throat swab samples were put into 150 µl viral protective solution for further molecular examinations. based on the who interim guidance (6), a confirmed case of covid19 is defined as a person with a positive result for rt-pcr test for sars-cov-2. the current study was performed according to the principles of the declaration of helsinki. an ethical approval was obtained from ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.retech.1399.115). 2.2. participants this study included all patients aged 18 years and above admitted to the hospital with typical covid-19 symptoms and a positive throat swab covid-19 test in evaluations. convenience sampling method was used. patients with previous neurocognitive disorders such as alzheimer’s disease and patients who were unconscious at the time of admission were excluded from the study. 2.3. data gathering demographic data (age, sex, body mass index (bmi)), history of comorbid diseases (diabetes mellitus, hypertension, chronic kidney disease, cardio and cerebrovascular disease, cancer), clinical symptoms (fever, dyspnea, cough, gastrointestinal discomforts, sore throat), laboratory findings, and neurological manifestations were gathered for all patients using hospital’s both electronic and written records. if there was missing data, data clarification was performed via phone call or consulting with related physicians. neurological manifestations were categorized into three classes: i. symptoms related to skeletal muscular injury; ii. central nervous system (cns) manifestations including headache, drowsiness, convulsion, ataxia, impaired consciousness, and acute cerebrovascular disease; iii. peripheral nervous system (pns) features such as nerve root pains and cranial nerve symptoms such as anosmia, ageusia, visual discomforts, and photophobia. critical cases were defined as those admitted to intensive care unit (icu) with acute respiratory distress syndrome (ards) criteria consisting of severe dyspnea, respiratory rate ≥30/minute, blood oxygen saturation ≤80%, pao2/fio2 ratio and unstable vital signs (7). trained medical students were responsible for data gathering. 2.4. statistical analysis data were presented as mean ± standard deviation (sd) for normally distributed, median (q1 – q3) for skewed variables, and frequency (percent) for categorical data. normality assumption was checked using kolmogorov-simonov test. mean and median differences were tested using independent t-test and mann-whitney u test, respectively. the distribution of categorical data was assessed using chisquare test (with exact p-value). p<0.05 was considered as significance level and all statistical analyses were performed using ibm spss statistics 23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e34 figure 1: the frequency of neurological manifestations in patients with covid-19. 3. results 727 covid-19 patients with the mean age of 49.94 ± 17.49 years (22 91) were enrolled (56.9% male). at least one neurologic symptom was observed in 403 (55.4%) cases. figure 1 displays the prevalence of neurological manifestations in the studied participants. headache (29.0%), and smell (22.3%) and taste impairment (22.0%) were the most prevalent neurologic symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. table 1 compares the baseline characteristics and laboratory findings of studied cases between cases with and without neurological manifestations. patients with neurological manifestations were significantly older (p = 0.04), had greater bmi (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to covid-19 patients without neurological symptom. o2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). in addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (nlr) (p = 0.02) and c-reactive protein (crp) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. 85 (11.7%) cases were critically ill and admitted to icu. table 2 compares the prevalence of neurologic manifestations between stable and critically ill patients. the prevalence of neurologic manifestations was not significantly different between stable and critically ill patients except for headache and dizziness, which were higher in stable patients (30.2% vs 20.0%, p=0.049 and 20.6% vs 9.4%, p= 0.014, respectively). 4. discussion herein, neurological symptoms of 727 hospitalized patients with covid-19 were evaluated. overall, 403 (55.4%) patients had at least one of the reported neurological symptoms. among all neurological symptoms, headache (29.0%) and smell impairment (22.3%) were the most prevalent ones. neutrophil count, nlr, and crp were significantly higher in patients with neurological manifestations. moreover, the prevalence of neurologic manifestations was not significantly different between stable and critically ill patients except for headache and dizziness, which were more prevalent in stable patients. according to the literature, among gastrointestinal disturbances in covid-19, anorexia is the most prevalent one (8), which is parallel to our findings. anorexia is probably due to the release of inflammatory cytokines along with the adverse effects of various drugs consumed by these patients. headache is also a prominent feature in covid-19 patients, which has been described among the most prevalent neurological symptoms by many studies (3, 9-11). it may occur due to systemic inflammation or virus invasion to brain blood vessels. about a quarter of patients reported smell and taste impairment without significant difference between critical and stable groups. we found that patients with neurological symptoms were significantly older (p = 0.005), had higher bmi (p = 0.02), longer hospitalization (p = 0.002), and longer first symptom to admission duration (p < 0.001) compared to covid-19 patients without neurological symptoms. in a study in china, it was shown that obese patients were at greater risk of developing severe covid-19 infection compared to normal-weight patients and this is of great importance, because it may indeed lead to increased hospitalization and worse clinical outcomes (12). the prevalence of neurologic manifestations was not significantly different between stable and critically ill patients except for headache and dizziness, which were more prevalent in stable patients. this may be related to the fact that critically ill patients are commonly bedridden and headache and dizziness are commonly triggered by walking. up to now, several studies have been performed to identify and characterize covid-19 pathophysiologic mechanisms leading to its neurological manifestations. a study by m. fotuhi et al. categorized neurological symptoms into a conceptual framework of their own so-called “neurocovid staging”, which included 3 stages. in the proposed neurocovid stage i infection with sars-cov2 is limited to nasal and gustatory epithelial cells and the cytokine storm is limited. then, in the neurocovid stage ii, there is a vigorous cytokine storm resulting in a hypercoagulable state, which is also responsible for blood clot formation and higher probability of strokes in these patients. finally, during the neuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. ashrafi and et al. 4 table 1: comparing the baseline characteristics and laboratory findings of covid-19 patients between cases with and without neurological manifestations variables neurological manifestation p no (n = 324) yes (n = 403) age (years) mean ± sd 48.50 ± 17.31 51.10 ± 17.57 0.04 sex female 138 (42.6) 175 (43.4) 0.82 male 186 (57.4) 228 (56.6) bmi (kg/m2) mean ± sd 25.71 ± 4.52 26.54 ± 4.26 0.02 habit smoke (yes) 42 (13.0) 39 (9.7) 0.16 ex-smoke (yes) 20 (6.2) 38 (9.4) 0.11 alcohol (yes) 8 (2.5) 6 (1.5) 0.34 opium (yes) 2 (0.6) 11 (2.7) 0.03 hospitalization (day) 1 (0 – 4) 1 (0 – 4) 0.22 first symptom to admission (day) 2 (1 – 4) 4 (2 – 8) <0.001 vital signs heart rate (/minute) 87.92 ± 13.71 88.56 ± 14.48 0.15 rr (/minute) 18.02 ± 3.53 18.72 ± 7.12 0.09 temperature (celsius) 37.32 ± 0.77 37.30 ± 0.79 0.70 o2 saturation (%) 94 (91 – 96) 93 (90 – 96) 0.04 sbp (mmhg) 116.68 ± 13.00 118.51 ± 14.35 0.08 dbp (mmhg) 74.27 ± 9.26 74.61 ± 9.33 0.64 laboratory findings wbc (/µl) 6.2 (4.4 – 8.5) 5.8 (4.6 – 8.1) 0.96 hemoglobin (g/dl) 13 (11.8 – 14) 13 (11.8 – 14.3) 0.55 platelet (/µl) 179 (139 – 214) 166 (131– 223) 0.54 neutrophil (/µl) 7.0 (6.0 – 8.0) 7.5 (6.5 – 8.3) 0.006 lymphocyte (/ µl) 2.5 (1.5 – 3.3) 2.1 (1.5 – 3.0) 0.03 nlr 2.8 (1.9 – 5.3) 3.5 (2.2 – 5.7) 0.02 plr 1.3 (0.9 – 1.7) 1.3 (0.9 – 1.9) 0.12 cr (mg/dl) 1.0 (0.9 – 1.3) 1.1 (1.0 – 1.4) 0.06 bun (mg/dl) 13 (11– 17.8) 14 (11 – 18) 0.31 crp (mg/dl) 15.0 (7.4– 34.0) 25.0 (11 – 45.3) 0.001 cpk (iu/l) 110 (60.3 – 162.8) 118 (61 – 256) 0.13 ldh (u/l) 495 (373 – 599) 495 (399 – 629) 0.55 data are presented as mean ± standard deviation, median (q1 – q3), or frequency (%). bmi: body mass index; rr: respiratory rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; wbc: white blood cells; nlr: neutrophil-to-lymphocyte ratio; plr: platelet-to-lymphocyte ratio; cr: creatinine; bun: blood urea nitrogen; crp: c-reactive protein; cpk: creatine phosphokinase; ldh: lactate dehydrogenase. rocovid stage iii, virus-induced cytokine storm damages the blood brain barrier resulting in the penetration of inflammatory factors and consequent severe complications including delirium, encephalopathy, and seizure (5). in a recent review by ellul et al., it was stated that acute ischemic stroke might occur due to a destabilized carotid plaque or as a result of atrial fibrillation. viral replication in the cerebral blood vessels could be a possible reason for such manifestations (13). it seems that covid-19 is also related with chronic neurologic complications, particularly a greater risk of stroke, even in youths. in a case-series by ashrafi et al. all six covid-19 patients presenting with stroke were younger than 55 and did not have any major risk factors for stroke (14). moreover, covid-19 patients are more prone to anxiety, which is even more prevalent among patients with preexisting comorbidities such as parkinson. further studies should be performed to evaluate the correlation between neurological comorbidities and anxiety during the covid-19 pandemic (15). this might be the result of sars-cov-2 directly attacking the cns as the virus was also found in the csf fluid. cytokine storm may also be responsible for these neurological symptoms particularly by resulting in a hypercoagulable state. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e34 table 2: comparison of neurological manifestations of covid-19 patients between critically ill patients and others variables critically ill p no (n = 642) yes (n = 85) neck pain 25 (3.9) 4 (4.7) 0.77 headache 194 (30.2) 17 (20.0) 0.05 impaired consciousness 72 (11.2) 13 (15.3) 0.27 dizziness 132 (20.6) 8 (9.4) 0.014 ataxia 48 (7.5) 2 (2.4) 0.08 seizure 6 (0.9) 2 (2.4) 0.24 smell impairment 147 (22.9) 15 (17.6) 0.27 taste impairment 143 (22.3) 17 (20.0) 0.63 sleep disturbances 124 (19.3) 15 (17.6) 0.82 neuralgia 21 (3.3) 4 (4.7) 0.52 stroke 13 (2.0) 4 (4.7) 0.13 total* 362 (56.4) 41 (48.2) 0.16 *at least one of the measured neurological symptoms was observed. data are presented as frequency (%). 5. limitations some of the neurological features such as encephalitis, encephalopathy, acute disseminated encephalomyelitis (adem) and myelitis might not be diagnosed at the time of hospitalization as they will manifest later. however, in cases with impaired consciousness, infection with sars-cov-2 is not the only trigger and other possible causes like drugs, toxins and metabolic derangement should also be considered. furthermore, admission to the intensive care unit is an important risk factor, as critical states like sepsis may result in neurological manifestations such as encephalopathy. 6. conclusion according to our findings, more than half of covid-19 patients had at least one of the studied neurological symptoms. this prevalence was significantly higher in older age, grated bmi, longer lasting disease, and opium usage. 7. declarations 7.1. conflict of interest the authors declare that they have no competing interests. 7.2. acknowledgments none. 7.3. funding and support not applicable. 7.4. authors’ contributions f.a.: conceptualization & study design, reviewing and editing, supervision d.o.: conceptualization & study design, writing – original manuscript a.z.: conceptualization & study design, methodology, supervision s.k.: literature search, writing – original manuscript, reviewing and editing a.s.: literature search, writing – original manuscript, reviewing and editing m.a.: writing – original manuscript, reviewing and editing, supervision b.b.: methodology, writing – original manuscript s.n.: conceptualization & study design, methodology f.s.: methodology, literature search, reviewing and editing a.f.: data curation & interpretation, methodology m.s.: methodology, reviewing and editing, supervision r.j.k.: conceptualization & study design, literature search m.v.: literature search, writing – original manuscript n.a.y.: writing – original manuscript, reviewing and editing s.h.t.: conceptualization & study design, data curation & interpretation e.s.: methodology, reviewing and editing references 1. fu l, wang b, yuan t, chen x, ao y, fitzpatrick t, et al. clinical characteristics of coronavirus disease 2019 (covid-19) in china: a systematic review and metaanalysis. j infect. 2020;80(6):656-65. 2. bohmwald k, galvez nms, rios m, kalergis am. neurologic alterations due to respiratory virus infections. front cell neurosci. 2018;12:386. 3. mao l, jin h, wang m, hu y, chen s, he q, et al. neurologic manifestations of hospitalized patients with coronavirus disease 2019 in wuhan, china. jama neurol. 2020. 4. wu y, xu x, chen z, duan j, hashimoto k, yang l, et al. nervous system involvement after infection with covidthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. ashrafi and et al. 6 19 and other coronaviruses. brain behav immun. 2020. 5. fotuhi m, mian a, meysami s, raji ca. neurobiology of covid-19. j alzheimers dis. 2020. 6. organization wh. clinical management of severe acute respiratory infection when novel coronavirus (ncov ) infection is suspected: interim guidance. 2020. 7. organization wh, organization wh. report of the whochina joint mission on coronavirus disease 2019 (covid19). geneva; 2020. 8. tian y, rong l, nian w, he y. review article: gastrointestinal features in covid-19 and the possibility of faecal transmission. aliment pharmacol ther. 2020;51(9):84351. 9. ahmad i, rathore fa. neurological manifestations and complications of covid-19: a literature review. j clin neurosci. 2020;77:8-12. 10. whittaker a, anson m, harky a. neurological manifestations of covid-19: a systematic review and current update. acta neurol scand. 2020;142(1):14-22. 11. correia ao, feitosa pwg, de sousa moreira jl, nogueira sár, fonseca rb, nobre mep. neurological manifestations of covid-19 and other coronaviruses: a systematic review. neurology, psychiatry and brain research. 2020. 12. cai q, chen f, wang t, luo f, liu x, wu q, et al. obesity and covid-19 severity in a designated hospital in shenzhen, china. diabetes care. 2020;43(7):1392-8. 13. cai q, chen f, wang t, luo f, liu x, wu q, et al. obesity and covid-19 severity in a designated hospital in shenzhen, china. diabetes care. 2020;43(7):1392-8. 14. ashrafi f, zali a, ommi d, salari m, fatemi a, arabahmadi m, et al. covid-19-related strokes in adults below 55 years of age: a case series. neurological sciences. 2020:1-5. 15. salari m, zali a, ashrafi f, etemadifar m, sharma s, hajizadeh n, et al. incidence of anxiety in parkinson’s disease during the coronavirus disease (covid-19) pandemic. mov disord. 2020;35(7):1095-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e33 https://doi.org/10.22037/aaem.v9i1.1123 or i g i n a l re s e a rc h factors related to mortality in patients with fournier’s gangrene or necrotising fasciitis; a 10-year crosssectional study anahita ansari djafari1, amirhossein rahavian2, babak javanmard3, saeed montazeri3 vahid shahabi3, seyyed ali hojjati3, saleh ghiasy3, ramin hamidi4, jalaluddin khoshnevis5∗ 1. laser application in medical sciences research center, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. andrology research center, yazd reproductive sciences institute, shahid sadoughi university of medical sciences, yazd, iran. 3. urology department, shohada-e-tajrish hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 4. school of medicine, 501 hospital (imam reza), aja university of medical science, tehran, iran. 5. clinical research development unit, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2021; accepted: february 2021; published online: 17 april 2021 abstract: introduction: fournier’s gangrene (fg) is a life-threatening disease, even with early diagnosis and administration of vigorous treatment, its mortality rate is high. this study aimed to evaluate the factors relate to mortality in patients with fg or necrotising fasciitis managed in a referral center. methods: this retrospective crosssectional study was conducted on patients managed in a tertiary referral center, tehran, iran, from march 2009 to march 2019, with diagnosis of fg or necrotising fasciitis. the correlation between different demographic and clinical parameters with mortality was analysed and reported. results: 73 cases with the mean age of 59.1 ± 15.8 (range: 25 – 88) years were studied (87.7% male). 21 (28.8%) patients died. escherichia coli (26 cases, 35.6%) was the most frequent microorganism in cultures. non-survived cases had higher mean age (p = 0.01), higher frequency of hyperlipidaemia (p = 0.02), immunosuppression (p < 0.001), longer hospital stay (p=0.02), lower blood pressure (p=0.01), and lower platelet count (p=<0.001). based on multivariate analysis, age (p = 0.015; odds: 0.88 (0.79-0.97)), haematocrit level (p = 0.01; odds: 1.27 (1.04-1.55)), platelet count (p = 0.03; odds: 10.11 (1.14-89.35)), and immunosuppression (p = 0.01; odds: 0.01 (0.0-0.54)) were independent related factors of mortality. conclusion: the rate of mortality due to fg and necrotizing fasciitis was 28.8%. based on multivariate analysis, the independent related factors of mortality were older age, lower haematocrit level and platelet count, and presence of immunosuppression. keywords: fournier’s gangrene; fournier’s gangrene severity index; mortality; thrombocytopenia cite this article as: ansari djafari a, rahavian a, javanmard b, montazeri s, shahabi v, hojjati s a, ghiasy s, hamidi r, khoshnevis j. factors related to mortality in patients with fournier’s gangrene or necrotising fasciitis; a 10-year cross-sectional study. arch acad emerg med. 2021; 9(1): e33. 1. introduction fournier’s gangrene (fg) is a rapidly progressive, lifethreatening necrotising infection of soft tissues, which typically involves the external genitalia and perineal area, but ∗corresponding author: jalaluddin khoshnevis; clinical research development unit of shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. tel: 00989134514983, email: amirrahavian1369@gmail.com, orcid: https://orcid.org/0000-0003-4173-2673. can also affect the abdominal wall and thighs (1). the disease mortality rate remains high despite early surgical interventions and advances in intensive care and medical treatment, due to its rapidly progressive nature (2-4). in recent decades, several studies published in the medical literature have examined the diverse scoring systems used to predict the risk of mortality in these patients (5, 6). one of these scores is fournier’s gangrene severity index score (fgsi). fgsi incorporates nine clinical and para-clinical parameters, including temperature, heart rate, respiratory rate, serum sodium, serum potassium, serum creatinine, leukothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ansari djafari and et. al 2 cyte count, haematocrit and arterial blood level of bicarbonate (7). some studies confirmed the efficacy of fgsi (8) and lin et al. introduced simplified fgsi including creatinine, hematocrit and serum potassium (9). in contrast, some studies concluded that this score cannot predict the mortality rate (10). moreover, it seems that other parameters and laboratory data are also capable of effectively predicting the prognosis in such septic patients (11). the medical literature has also reported several other clinical factors related to the increased mortality risk in patients with fg. some of these factors include primary anorectal cancer, immunosuppression, senectitude, delay in treatment initiation, and hepatic dysfunction (12, 13). the aim of this study was to evaluate the factors related to mortality in patients with fg or necrotising fasciitis managed in a referral urology center, over the past ten years. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on patients managed in a tertiary referral center, tehran, iran, from march 2009 to march 2019, with diagnosis of fournier’s gangrene or necrotising fasciitis. the correlation between different demographic and clinical parameters with mortality was analysed and reported. the ethical committee of the hospital approved this study and permitted us to review patients’ medical data (ir.sbmu.retech.rec.1398.476). the patients’ health records were anonymised. 2.2. data gathering the source of data was the medical profile of patients, which was searched using terms such as fournier’s gangrene, soft tissue infection, and necrotising fasciitis. the collected medical data included sex, age, co-morbidities (diabetes mellitus, cerebrovascular accidents, malignancies, urinary incontinence, bed ridden), laboratory findings, duration of hospital stay, antibiotics used in the treatment, immune system status and the final outcome. disease diagnosis was based on the symptoms of pain, erythema, ulcers, swelling, crepitus, necrosis, purulent discharge and later confirmation by tissue inspection in the operating room. also, vital signs (pulse rate, respiratory rate, blood pressure and temperature) were assessed for signs of systemic inflammatory response syndrome. in addition, fournier’s gangrene severity index (fgsi), which incorporates nine variables (temperature, heart rate, respiratory rate, serum sodium, serum potassium, serum creatinine, haematocrit, white blood cell count, and serum bicarbonate), was calculated for all patients (3). the patients were classified, according to the extent of fg, in to the following groups: 1) patients with gangrene confined to the scrotum, 2) patients with penile and scrotal gangrene, 3) patient with scrotal gangrene extending to the perineum, 4) patient with scrotal gangrene extending to the abdominal wall or thighs. patients with solitary abscess as well as those with soft tissue infection without perineal or scrotal involvement were excluded from the study. patients with incomplete data were also omitted. mortality was described as disease-related death during the hospital stay. two urology residents read the records and gathered the data and finally, the corresponding author verified the data. 2.3. statistical analysis statistical analysis was performed using statistical package for the social sciences version 26. first, the normality of data was checked and independent t-test and mann-whitney test were used according to the type of hypothesis. quantitative outcomes were shown using descriptive statistics (mean ± standard deviation) and qualitative variables were reported as frequency (%). regression analysis was performed to determine the association of risk factors and mortality of fg. a p-value less than 0.05 was considered statistically significant. 3. results 106 patients with fg or necrotising fasciitis were admitted to the studied hospital during the study period. 33 cases were excluded because of insufficient data. 73 cases with the mean age of 59.1 ± 15.8 (range: 25 – 88) years were studied (87.7% male). 21 (28.8%) patients died. the most commonly involved area was perineum. all cases were treated with surgical debridement of necrotic tissues, in 21(28.8%) of whom debridement was extensive enough to necessitate additional tissue reconstruction (flap (3 cases), tissue graft (6 cases), and secondary suturing (12 cases)). the results of wound culture were available for 52 patients and escherichia coli (26 cases, 35.6%) was the most frequent microorganism. all four patients whose wound cultures were positive for klebsiella, proteus, pseudomonas and acinetobacter died. non-survived cases had higher mean age (p = 0.01), higher frequency of hyperlipidaemia (p = 0.02), immunosuppression (p < 0.001), longer hospital stay (p=0.02), lower blood pressure (p=0.01), and lower platelet count (p=<0.001). seven patients had platelet counts of <50000/mm³, six of whom died. regarding fgsi variables, non-survived patients had lower serum haematocrit (p=0.0), lower serum bicarbonate (p=0.0), and higher respiratory rate (p=0.03). the mean fgsi score was 8.7±3.5 in dead and 3.5 ± 2.9 in survived cases (p < 0.0001). 50 (96.2%) survived cases and 11 (42.4%) dead cases had fgsi ≤ 9. 10 (47.6%) non-survived cases had fgsi > 9. table 1 compares the baseline characthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e33 teristics of participants between survived and non-survived cases. table 2 shows the factors related to mortality based on the multivariate analysis. based on this analysis, age, haematocrit level, platelet count, and immunosuppression were independent factors related to mortality. 4. discussion this study investigated 73 cases of fg or necrotising fasciitis who were hospitalised in our center over a 10-year period. the rate of mortality amongst our fg patients was 28.8%. based on multivariate analysis, the independent related factors of mortality were older age, lower haematocrit level and platelet count, and presence of immunosuppression. the mean age of survivors and deceased patients was significantly different; also, in multivariate analysis, we showed that age had a direct effect on mortality of the patients. some published studies show similar results (7), whilst the result of others is contradictory to ours (4, 14). tuncel et al. reported a correlation between diabetes mellitus (dm) and poor prognosis in fg patients (10), but corcoran et al. found no similar association in their research (8). in this study, there was no significant difference between the frequency of dm amongst survivors and patients who died. the frequency of hyperlipidaemia and immunosuppression, was significantly different between survived and non-survived cases (p = 0.02 and p < 0.001, respectively). e. coli, streptococcus, staphylococcus, enterococcus and bacteroides genera were the most common bacteriological microorganisms that had been isolated from fg patients in previous studies (15, 16). in this study, the bacteriological agents most frequently detected in the wound cultures corresponded to those reported in medical literature and included e. coli, as well as streptococcus, staphylococcus. in rare cases, enterococcus and pseudomonas species were isolated. in contrast, the results of wound culture were negative, with no causative agent detected, in 21 (28.8%) cases. this is probably due to an anaerobic microbial growth that could not be isolated using our culture conditions. no clear consensus exists on the most reliable clinical parameters for prediction of poor prognosis in fg patients (15). fgsi has been developed to facilitate the prediction of fg outcomes in affected patients. laor et al. found that an fgsi score of >9 corresponded to 75% probability of a lethal outcome, while a score of ≤9 correlated with 78% survival probability (3). this threshold for the prediction of patient mortality was also confirmed in other studies (14, 17). in this study, the mean fgsi score in deceased cases was significantly higher, which was consistent with other studies (7, 8, 18). notwithstanding the significantly higher mean fgsi score in the deceased patient group, only 47.6% of patients who died had fgsi>9. yeniyol et al. found that deceased patients had elevated serum levels of urea, creatinine, alkaline phosphatase, and lactate dehydrogenase, and high leukocyte counts, while their levels of sodium, potassium, hco3, haematocrit, total protein, and albumin were lower than the survivors’(14). clayton et al. found that amongst various variables, a blood urea nitrogen level of higher than 50 mg/dl was the most significant factor in predicting fg mortality (19). in the study conducted by tsung-yen lin, only serum creatinine, potassium and haematocrit levels showed notable association with the risk of patient mortality (9). in our study, respiratory rate, haematocrit, and hco3 level were found to be significantly different between survivors and deceased patients. thrombocytopenia increased bleeding tendency and susceptibility to infection (20) and multiple studies pointed to the relationship between thrombocytopenia and likelihood of death in sepsis (21, 22). mean platelet counts of survivors and deceased patients was in a normal range but deceased patients had significantly lower mean platelet counts (135400±77600/mm3 vs. 256700±136800/mm³, p = 0.0001). platelet counts of seven patients were <50000/mm3, six of whom died. according to our findings, some of the nine parameters incorporated in fgsi were not significantly different between deceased and survived fg patients. however, some other factors including age, thrombocytopenia, and especially platelet counts <50000/mm3 were found to be predictive of mortality risk in these patients. therefore, more studies using larger sample sizes are required to further evaluate these parameters in order to facilitate the development of a more efficacious fg scoring model. 5. limitations one of the limitations of our study is that due to incomplete files and the retrospective fashion of the study, we had to exclude many cases before data analysis, so it reduced our sample size. nevertheless, this sample size is one of the largest sample sizes for this rare disease. 6. conclusion the rate of mortality of fg and necrotizing fasciitis was 28.8% in this study. based on multivariate analysis, the independent factors related to mortality were older age, lower haematocrit level and platelet count, and presence of immunosuppression. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ansari djafari and et. al 4 table 1: comparing the baseline characteristics between survived and non-survived patients with fournier’s gangrene or necrotising fasciitis variables died (n = 21) survived (n = 52) p value sex male 16 (76.2) 48(92.4) 0.07 female 5 (23.8) 4(7.6) age (years) mean ± sd 66.2 ± 11.1 56.1 ± 16.5 0.01 medical history diabetes mellitus 11(52.3) 23(44.2) 0.35 hyperlipidaemia 4(19.0) 1(1.9) 0.02 immunosuppression 11(52.3) 7(13.4) <0.001 colorectal or urological surgeries 4(19.0) 16(30.7) 0.38 presenting vital sign temperature (◦c) 37.4 ±0.7 37.3 ±0.8 0.90 respiratory rate (/minute) 19.2 ±4.8 16.8 ±1.8 0.03 pulse rate (beats/minute) 89.2±16.87 83.8±10.9 0.10 systolic blood pressure 114.2±16.3 124.9±17 0.01 laboratory findings serum creatinine (mg/dl) 2.8 ±1.8 1.7±2.9 0.06 serum sodium (mm) 134.5 ±7.3 137 ±4.8 0.10 serum potassium(mm) 4 ±0.6 4 ±0.4 0.70 haematocrit (%) 27.1 ±5.1 33.5 ±5.5 < 0.001 white blood cells (103 /µl) 16.1 ±8.8 15.1 ±6.7 0.6 serum hco3 (mm) 17.2 ±6.2 23 ±6.1 < 0.001 platelet (/mm3 ) 135400±77600 256700±136800 < 0.001 site of involvement scrotum 1(4.7) 15(28.8) penis 0(0.0) 4(7.6) perineum 7(33.3) 13(25.0) 0.30 perianal 9(42.8) 9(17.3) abdomen 4(19) 11(21.1) hospital stay (days) mean ± sd 18.0 ± 22.6 10.1 ± 7.1 0.02 data are presented as mean ± standard deviation or frequency (%). table 2: independent factors related to mortality in patients with fournier’s gangrene or necrotising fasciitis independent factors p-value odds ratio (95% ci*) age 0.015 0.88 (0.79-0.97) haematocrit 0.01 1.27 (1.04-1.55) immunosuppression 0.03 10.11(1.14-89.35) platelet > 50000 0.02 0.01 (0.0-0.54) *ci: confidence interval. 7. declarations 7.1. author contribution aad: conception and design, critical revision of the manuscript for important intellectual content, supervision ar: analysis and interpretation of data, statistical analysis bj: administrative, technical or material support, supervision sm: drafting of the manuscript vs: acquisition of data, analysis and interpretation of data sah: acquisition of data sg: drafting of the manuscript rh: drafting of the manuscript, supervision jk: conception and design, critical revision of the manuscript for important intellectual content, administrative, technical or material 7.2. support supervision all authors have read and approved the manuscript. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e33 7.3. data availability authors guarantee that data of the study are available and will be provided if anyone needs them. 7.4. conflict of interests none. 7.5. funding none. 7.6. acknowledgements we thank all our patients and their relatives. also, we thank all of the staff members of the department of urology and our hospital for their help. references 1. clark jc, lan vm. heart failure patient learning needs after hospital discharge. applied nursing research. 2004;17(3):150-7. 2. tahmasebi h, mahmoodi g, mokhberi v, hassani s, akbarzadeh h, rahnamai n. the impact of aromatherapy on the anxiety of patients experiencing coronary angiography. zahedan j res med sci. 2012;14(3):e93565. 3. black jm, hawks jh, keene am. medical-surgical nursing: clinical management for positive outcomes: wb saunders; 2001. 4. niknejad r, mirmohammad-sadeghi m, akbari m, ghadami a. effects of an orientation tour on 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in patients with chest pain in the emergency department: a stepped-wedge, cluster randomized trial. annals of internal medicine. 2017;166(10):68997. 14. mahler sa, hiestand bc, goff jr dc, hoekstra jw, miller cd. can the heart score safely reduce stress testing and cardiac imaging in patients at low risk for acute coronary syndrome? critical pathways in cardiology. 2011;10(3):128. 15. six aj, cullen l, backus be, greenslade j, parsonage w, aldous s, et al. the heart score for the assessment of patients with chest pain in the emergency department: a multinational validation study. critical pathways in cardiology. 2013;12(3):121-6. 16. melki d, jernberg t. heart score: a simple and useful tool that may lower the proportion of chest pain patients who are admitted. critical pathways in cardiology. 2013;12(3):127-31. 17. gharaee r, zohari anboohi s, shiri h, nasiri m. comparison of triage effectiveness based on esi and heart scale in diagnosis of outcome in patients with chest pain. journal of babol university of medical sciences. 2019;21(1):299-305. 18. backus b, six a, kelder j, bosschaert m, mast e, mosterd a, et al. a prospective validation of the heart score for chest pain patients at the emergency department. international journal of cardiology. 2013;168(3):2153-8. 19. leite l, baptista r, leitão j, cochicho j, breda f, elvas l, et al. chest pain in the emergency department: risk stratification with manchester triage system and heart score. bmc cardiovascular disorders. 2015;15(1):1-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e30 or i g i n a l re s e a rc h rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative study babak nakhjavan-shahraki1, masoud baikpour2, mahmoud yousefifard3, zahra sadat nikseresht2, samaneh abiri4, jalaledin mirzay razaz5, gholamreza faridaalaee6, mahboob pouraghae7, sahar shirzadegan7, mostafa hosseini8∗ 1. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. 2. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 3. physiology research center and department of physiology, faculty of medicine, iran university of medical sciences, tehran, iran. 4. department of emergency medicine, jahrom university of medical sciences, jahrom, iran. 5. department of community nutrition, faculty of nutrition and food technology, shahid beheshti university of medical sciences, tehran, iran. 6. department of emergency medicine, maragheh university of medical sciences, maragheh, iran. 7. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. 8. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: november 2016; accepted: november 2016; published online: 10 january 2017 abstract: introduction: rapid acute physiology score (raps) and rapid emergency medicine score (rems) are two physiologic models for measuring injury severity in emergency settings. the present study was designed to compare the two models in outcome prediction of trauma patients presenting to emergency department (ed). methods: in this cross-sectional study, the two models of raps and rems were compared regarding prediction of mortality and poor outcome (severe disability) of trauma patients presenting to the eds of 5 educational hospitals. the discriminatory power and calibration of the models were calculated and compared using stata 11. results: 2148 patients with the mean age of 39.50±17.27 years were studied (75.56% males). the area under the curve of rems and raps in predicting in-hospital mortality were 0.93 (95% ci: 0.92-0.95) and 0.899 (95% ci: 0.86-0.93), respectively (p=0.02). these measures were 0.92 (95% ci: 0.90-0.94) and 0.86 (95% ci: 0.83-0.90), respectively, regarding poor outcome (p=0.001). the optimum cut-off point in predicting outcome was found to be 3 for rems model and 2 for raps model. the sensitivity and specificity of rems and raps in the mentioned cut offs were 95.93 vs. 85.37 and 77.63 vs. 83.51, respectively, in predicting mortality. calibration and overall performance of the two models were acceptable. conclusion: the present study showed that adding age and level of arterial oxygen saturation to the variables included in raps model can increase its predictive value. therefore, it seems that rems could be used for predicting mortality and poor outcome of trauma patients in emergency settings. keywords: multiple trauma; trauma severity indices; decision support techniques; prognosis; patient outcome assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: nakhjavan-shahraki b, baikpour m, yousefifard m, nikseresht z, abiri s, mirzay razaz j, faridaalaee gh, pouraghae m, shirzadegan, s, hosseini m. rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative study. emergency. 2017; 5(1): e30. ∗corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 2 1. introduction a ppropriate and timely management is strongly associated with a decrease in morbidity and mortality rates in trauma patients (3). emergency physicians provide one of the main levels of care in management of trauma patients. however, the constant overcrowding of emergency departments (ed) might deprive the physicians and nurses of the time for appropriate management of patients. in this regard, one of the best ways to perform a quick assessment of the patients and take necessary measures accordingly is appropriate application of scoring systems (4-11). application of screening tools to lower the time needed for assessment of patients can considerably improve the quality of care (12), increase the efficacy of treatments and lower morbidity and mortality rates. various scoring systems have been developed and undergone gradual modifications throughout decades to increase their efficacy, accuracy and validity. despite the improvements in these scoring systems, unfortunately they still have few shortcomings (13) and using them can be associated with multiple limitations. these limitations include the need for complicated calculations, the great number of variables they assess, and sometimes lack of validity evaluation in different clinical settings. therefore, research in this field is still in progress and each year some new models are developed. in recent years, health organizations have suggested to develop a physiologic scoring system for early detection of high-risk patients in order to regulate management of trauma patients and consequently, lower the burden of trauma injuries (14). one of these scoring systems was the rapid acute physiology score (raps), the abbreviated version of the acute physiology and chronic health evaluation (apache ii) score in which physiologic variables including the heart rate, blood pressure, respiratory rate and glasgow coma scale (gcs) were considered as prognostic factors in trauma patients. although the prognostic value of this model has been found to be acceptable for clinical use, researchers are still trying to improve its accuracy (19). the other recently presented model is rapid emergency medicine score (rems). this model incorporates the level of arterial oxygen saturation (o2 sat) and chronological age of patients with the variables included in the raps model and was initially proposed for predicting mortality in non-surgical patients admitted to ed (19, 20). however, the validity of this model in trauma patients has been evaluated in only a few studies. since a limited number of variables have been included in raps and rems models, assessing and calculating the score based on them is feasible and they can be easily used in eds. however, only a few studies have compared the two models with each other (19) and disagreements still exist on which one to use when assessing a trauma patient. accordingly, the present study aimed to assess and compare the prognostic value of raps and rems models for in-hospital mortality and poor outcome of trauma patients presenting to ed. 2. methods 2.1. study design and setting in this cross-sectional study, the two models of raps and rems were compared in predicting the in-hospital mortality and poor outcome (severe disability based on glasgow outcome scale) in trauma patients presenting to ed. the study protocol was evaluated and approved by the ethics committee of tehran university of medical sciences. the authors adhered to the guidelines proposed by the declaration of helsinki throughout the study. the patients or their family members signed an informed written consent for participating in the study. 2.2. participants data were gathered prospectively from eds of 5 educational hospitals in iran (tehran, tabriz, urmia, jahrom and ilam) from may to october 2016. trauma patients aged over 18 years old referring to ed were included through a convenience sampling method. pregnant women and patients who expired at the event scene were excluded. 2.3. data gathering in each ed, an emergency medicine physician prospectively gathered data on demographic characteristics of the patients (age, gender and trauma mechanism), their signs and symptoms and findings of their physical examination and recorded the information in data collection forms. these data included all the factors needed for calculating raps and rems models (19). gathered information included age, body temperature, systolic and diastolic blood pressures (from which the mean arterial pressure was calculated), heart rate, respiratory rate, level of oxygen saturation and the patient’s level of consciousness based on gcs. all these factors were measured for the patients on arrival and then they were followed during their admission to record their final outcome (expired vs. alive) and the condition in which they were discharged from the hospital (full recovery, moderate disability, severe disability or vegetative state). 2.4. outcome measurement the outcome of the patients on discharge from the hospital was evaluated using glasgow outcome scale (21). the primary outcome was in-hospital mortality and the secondary outcome was poor outcome defined as developing severe disabilities. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e30 figure 1: area under the curve (auc) of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome. 2.5. statistical analysis the minimum sample size was calculated to be 1894 patients considering an in-hospital mortality rate of 5.2% among trauma patients (22), a confidence interval of 95% (α=0.05), a power of 90% (β=0.1) and a maximum error of 1.5% in estimating the mortality rate (d=0.01). data were entered into spss software version 21.0 and were analyzed by stata 11.0 software. all the patients had two different scores based on rems and raps models. area under the receiving operating characteristics curve (auc), sensitivity, specificity, and positive and negative likelihood ratios with 95% confidence intervals (95% ci) were calculated for each model and subsequently the discriminatory power was evaluated. auc of the two models were compared based on the method proposed by cleves and rock (23). general calibration was assessed by drawing calibration plots, in which the number of observed versus predicted mortality or poor outcome per decile of the linear predictor of raps or rems models were compared. in this plot, the reference line, with an intercept of zero and a slope of one, shows perfect calibration. overall performance was also evaluated by assessing the predictive reliability and predictive accuracy through calculating brier score. finally, the spearman’s rank coefficient was calculated to assess the concordance between rems-predicted and raps-predicted percentage of mortality and poor outcome. a p<0.05 was considered as the level of significance in all the analyses. table 1: baseline characteristics of studied patients variable value age (year) 39.50 ± 17.27 gender(n, %) male 1623 (75.56) female 525 (24.44) mechanism of trauma motorcycle accident 591 (27.51) car rider accident 518 (24.12) pedestrian 378 (17.60) falls more than 3 meters 152 (7.08) falls less than 3 meters 201 (9.36) other 308 (14.34) gcs 14.4 ± 2.19 hr (beat/minute) 87.60 ± 15.63 sbp (mmhg) 115.38 ± 15.36 dbp (mmhg) 73.49 ± 10.07 o2 sat (%) 94.78 ± 5.80 temperature (celsius) 36.81 ± 0.90 rr (number/minute) 16.46 ± 6.15 outcome good recovery 1630 (75.88) moderate disability 342 (15.92) severe disability 53 (2.47) death 123 (5.73) data were presented as mean ± standard deviation or frequency and percentage; gcs: glasgow coma scale; hr: heart rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; o2 sat: arterial oxygen saturation; rr: respiratory rate. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 4 figure 2: calibration plots of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome. 3. results 3.1. baseline characteristics data from a total of 2148 patients were gathered. the mean age of included patients was 39.50±17.27 years and 75.56% of them were male. motorcycle accident (27.51%), car rider accident (24.12%) and the pedestrian (17.60%) were the most common mechanisms of injury. the mean values of vital signs, level of consciousness and arterial oxygen saturation in the studied trauma patients are presented in table 1. patients were discharged from the hospital with a good recovery and mild disability in 75.88% of cases, moderate disability in 15.92% and severe disability in 2.47% of them. eventually, 5.73% of the included patients expired. 3.2. discrimination figure 1 depicts the auc of raps and rems models in predicting mortality and poor outcome. the auc of rems and raps models in predicting in-hospital mortality were 0.93 (95% ci: 0.92-0.95) and 0.899 (95% ci: 0.86-0.93), respectively, and the difference between the two was found to be statistically significant (p=0.02). similarly, the auc of rems and raps in predicting poor outcome were calculated to be 0.92 (95% ci: 0.90-0.94) and 0.86 (95% ci: 0.83-0.90), respectively, with the differences being statistically significant (p=0.001). the optimum cut-off value for rems model in predicting mortality and poor outcome was 3 while this figure was found to be 2 for the raps model. screening performance characteristics of rems and raps models are presented in table 2. as can be seen, the sensitivity of rems model was considerably higher than raps (95.63 vs. 85.37), while its specificity was found to be lower than that of the raps model in predicting mortality (77.63 vs. 83.51). similar findings were yielded for predicting poor outcome in patients. since both of these models were developed for screening trauma patients, the model with a higher sensitivity would be more suitable for this purpose. therefore, it this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e30 figure 3: concordance between rapid emergency medicine score (rems) predicted and rapid acute physiology score (raps) predicted percentage of mortality and poor outcome. seems that the value of rems model in predicting mortality and poor outcome in trauma patients is higher than the raps model. 3.3. calibration figure 2 depicts the calibration plots of rems and raps models, showing acceptable curves for both models in predicting mortality and poor outcome. calibration plot of rems model in predicting in-hospital mortality had a slope and intercept of 0.98 and 0.001, respectively, while these figures were found to be 0.96 and 0.003, respectively, for predicting poor outcome. as for the raps model the calibration plot for predicting mortality had a slope and intercept of 1.01 and -0.0005 while these figures were calculated to be 1.009 and -0.0007, respectively, for predicting poor outcome. these plots indicate that both models are perfect in predicting both mortality and poor outcome in trauma patients. 3.4. overall performance brier score for rems model in predicting mortality was 0.034 and the scaled reliability was found to be 0.0004. for the raps model, these figures were calculated to be 0.028 and 0.0001, respectively. similar results were obtained on prediction of poor outcome. these findings confirm the high predictive accuracy and reliability of the two models (table 3). finally, concordance between rems and raps models was evaluated and a good correlation was observed in the predicted risk of mortality (r=0.77; p <0.001) and poor outcome (r=0.77; p<0.001) between the two models (figure 3). 4. discussion the findings of the present study showed that both rems and raps models have acceptable predictive values for mortality and poor outcome of adult trauma patients referring to eds. however, in comparison it seems that the rems model is slightly better than the raps model for this purpose. these findings were congruent with the results of the study conducted by olsson et al. that showed the rems model to be a strong predictor of in-hospital mortality in patients referring to eds and has a higher predictive value compared to raps model (24). these researchers aimed to assess the predictive value of rems model in three further studies, two of which indicated that this model is a strong tool for predicting mortality in non-surgical patients (19, 20). the third study showed that even with incorporation of the charlson comorbidity index in the analyses, the rems model has a high predictive value for mortality of non-surgical patients (25). in another study conducted on 3680 patients, imholff et al. showed that a higher rems score is associated with an increase in the mortality rate of trauma patients. these authors suggest that this scoring system is a simple and accurate predictor for in-hospital mortality of trauma patients (22). in their survey aiming to evaluate the role of rems model in predicting mortality of patients infected with vibrio vulnificus, kuo et al. also found that this model provides an acceptable predictive value for mortality of patients (26). ha et al. aimed to compare the prognostic performance of the two rems model and worthing physiological scoring system in predicting mortality of patients referring to eds and found that both models have acceptable prognostic perforthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. nakhjavan-shahraki et al. 6 table 2: screening performance characteristics of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of mortality and poor outcome characteristics mortality poor outcome rems raps rems raps true positive 118 105 162 136 true negative 1572 1691 1563 1669 false positive 453 334 409 303 false negative 5 18 14 40 sensitivity 95.93 (90.30-98.49) 85.37 (77.59-90.86) 92.04 (86.75-95.42) 77.27 (70.23-83.09) specificity 77.63 (75.74-79.42) 83.51 (81.80-85.08) 79.26 (77.39-81.02) 84.64 (82.95-86.18) positivelr 4.29 (3.92-4.69) 5.18 (4.58-5.85) 4.44 (4.03-4.89) 5.03 (4.41-5.72) negative lr 0.05 (0.02-0.12) 0.18 (0.11-0.27) 0.10 (0.06-0.17) 0.27 (0.20-0.35) ∗ data are presented as estimated value and 95% confidence interval. lr: likelihood ratio. table 3: overall performance of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome characteristics mortality poor outcome rems raps rems raps brier score 0.034 0.028 0.049 0.043 scaled reliability 0.0004 0.0001 0.0005 0.0003 mances, with the worthing physiological scoring system being slightly better that the rems model (27). bulut et al. evaluated 2000 patients and reported that although both models have moderate predictive values, but the prognostic value of rems model for mortality of patients referring to eds was significantly higher than modified early warning score (28). as can be seen, slight disagreements can be observed between the results of various studies considering the prognostic value of rems and raps models for mortality of patients, which can be attributed to the differences in settings of the surveys. various scoring systems have been developed for classification of injuries, which include physiologic and anatomic systems, specialized trauma scoring systems and combined scores (29). each of these systems has their own specific limitations and advantages, but a scoring system that is going to be used in the emergency settings should involve fewer variables and be easy to use. in this regard, the raps model, which includes few variables, might be a good candidate for application in emergency settings, but to increase its predictive value, the two variables of age and arterial oxygen saturation level were added to the model and the rems model was developed. results of the present study, based on calculated aucs, showed that predictive value of raps model for in-hospital mortality (auc=0.899) and poor outcome of patients (auc=0.86) were good, while the prognostic values of rems model were found to be excellent for mortality (auc=0.93) and poor outcome (p=0.92). the relatively large sample population and the multi-center setting can be considered as the strengths of the present study, which warrants its power. having included patients from five cities of tehran, tabriz, urmia, jahrom and ilam reassured the representativeness of the findings to the whole iranian population. accordingly, it seems that rems model has a higher value for predicting in-hospital mortality and poor outcome of trauma patients presenting to eds. 5. limitation employing a convenience sampling method suggests presence of selection bias in this study. another limitation of this survey was inclusion of body temperature in the analyses based on an axillary reading which might not be accurate particularly in overcrowded emergency settings and can affect the final interpretation of results. 6. conclusion the present study showed that adding age and the level of arterial oxygen saturation to the variables included in the raps model can increase its predictive value. therefore, it seems that rems could be used for predicting mortality and poor outcome of trauma patients in emergency settings. 7. appendix 7.1. acknowledgements the authors wish to acknowledge the cooperation of tehran, tabriz, urmia, jahrom and ilam emergency departments in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e30 providing patient data. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support this research has been supported by a tehran university of medical sciences and health services grant and sina trauma and surgery research center, tehran university of medical sciences grant (grant number: 94-0438-30757). 7.4. conflict of interest the authors report no declarations of interest. references 1. mehes m, abdullah f. global surgery and public health: a new paradigm. archives of surgery. 2011;146(10):12189. 2. mathers cd, loncar d. projections of global mortality and burden of disease from 2002 to 2030. plos med. 2006;3(11):e442. 3. shortell sm, zimmerman je, rousseau dm, gillies rr, wagner dp, draper ea, et al. the performance of intensive care units: does good management make a difference? medical care. 1994:508-25. 4. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, ghanbari mjh, et al. diagnostic accuracy of ultrasonography and 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https://doi.org/10.22037/aaem.v9i1.1065 or i g i n a l re s e a rc h the correlation between head of bed angle and intraabdominal pressure of intubated patients; a pre-post clinical trial sedigheh samimian1, sadra ashrafi2, tahereh khaleghdoost mohammadi3∗, mohammad reza yeganeh3, ali ashraf1, hamideh hakimi4, maryam dehghani5 1. clinical research development unit of poursina hospital, guilan university of medical sciences, rasht, iran. 2. student research committee, chronic kidney disease research center(ckdrc), shahid beheshti university of medical sciences, tehran, iran. 3. department of medical-surgical nursing, shahid beheshti faculty of nursing and midwifery, guilan university of medical sciences, rasht, iran. 4. department of nursing, lahijan branch, islamic azad university, lahijan, iran. 5. nahavand school of allied medical sciences, hamadan university of medical sciences, hamadan, iran. received: january 2021; accepted: february 2021; published online: 6 march 2021 abstract: introduction: the recommended position for measuring intra-abdominal pressure (iap) is the supine position. however, patients put in this position are prone to ventilator-associated pneumonia. this study was done to evaluate the relationship between bed head angle and iap measurements of intubated patients in the intensive care unit. methods: in this clinical trial, seventy-six critically ill patients under mechanical ventilation were enrolled. iap measurement was performed every 8 hours for 24 hours using the korn method in three different degrees of the head of bed (hob) elevation (0◦, 15◦ , and 30◦). bland-altman analysis was performed to identify the bias and limits of agreement among the three hobs. according to world society of the abdominal compartment syndrome (wsacs), we can consider two iap techniques equivalent if a bias of <1 mmhg and limits of agreement of 4 to +4 were found between them. data were analyzed using spss statistical software (v. 19), and the significance level was considered as 0.05. results: the prevalence of intra-abdominal hypertension was 18.42%. mean ± standard deviation (sd) of iap were 8.44 ± 4.02 mmhg for hob angle 0◦, 9.58 ± 4.52 for hob angle 15◦, and 11.10 ± 4.73 for hob angle 30o (p = 0.0001). the iap measurement bias between hob angle 0◦and hob angle 15◦ was 1.13 mmhg. this bias was 2.66 mmhg between hob angle 0◦ and hob angle 30◦. conclusion: elevation of hob angle from 0 to 30 degree significantly increases iap. it seems that the measurement of iap at hob angle 15◦ was more reliable than 30◦. keywords: pressure; intra-abdominal hypertension; head of bed; critical care; compartment syndrome; supine position cite this article as: samimian s, ashrafi s, khaleghdoost mohammadi t, yeganeh mr, ashraf a, hakimi h, dehghani m. the correlation between head of bed angle and intra-abdominal pressure of intubated patients; a pre-post clinical trial. arch acad emerg med. 2021; 9(1): e23. 1. introduction intra-abdominal pressure (iap) is increasingly considered an important pathological factor among the patients admitted ∗corresponding author: tahereh khaleghdoost mohammadi; 2nd floor, daneshjoo street, nursing department, shahid beheshti faculty of nursing and midwifery, guilan university of medical sciences, rasht, iran, postal code: 4146939841, email: khaleghdoost@gums.ac.ir, tel: +981333555056-8, fax: +981333550097, orcid: 0000-0002-9786-6374. to intensive care unit (icu) (1). elevated iap is a frequent cause of morbidity and mortality among icu patients (2). recurrent and pathological elevation of iap (≥12 mmhg) without organ dysfunction is called intra-abdominal hypertension (iah), and if it is associated with organ dysfunction, abdominal compartment syndrome (acs) occurs (3, 4) the prevalence of iah in intensive care patients has been reported as 18% to 58.8% (5, 6). this wide range of prevalence is due to the differences in clinical settings (surgical or medical) and conditions (trauma, burn and postoperative patients), this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimian et al. 2 the method chosen for iap measurement, and also the lower limit selected for iah definition (7). the clinical development of iah is a silent process and it is therefore, not diagnosed until its progress has become complete (8). the sensitivity of clinical examination in diagnosis of iah is only 40% to 60%, so iap should be measured periodically not to miss iah/acs diagnosis (2, 8). according to the recommendation of the world society of abdominal compartment syndrome (wsacs), iap should be routinely measured in patients with at least two iah risk factors (9). there are various methods to measure iap. the measurement of the intra-vesical pressure is recognized as the standard method of measuring iap according to wsacs (10, 11). the standard position for measuring iap is the supine position or zero degrees of the head of bed (hob). however, for the patients admitted to icu, this position is not desired, and it leads to unavoidable outcomes including ventilator-associated pneumonia (vap), respiratory distress, hemodynamic changes and so on, particularly when iap is continuously measured (2, 10, 12, 13). putting the patient in supine position is contrary to the policies recommended by centers for disease control (cdc). these policies prevent aspiration pneumonia and ventilatorassociated pneumonia. on the other hand, measurement of iap at 0◦ of hob, in case of patients’ intolerance and the existence of both abdominal and bladder muscle retraction, leads to the false increase of iap (1, 14, 15) or iap measurements at 0◦ of hob may underestimate or overestimate the iap that the patient is experiencing during the intervals of measurements (16, 17). there is some evidence that body position can affect measured iap values, but the effect of hob elevation degree, which is applied for changing the position of icu patients, is not clearly defined (18). this study was done in order to evaluate the relationship between bed head angle and iap measurements of intubated patients in the intensive care unit. 2. methods 2.1. study design and settings the current study is a clinical trial aimed to compare the changes of iap with hob angle at 0◦, 15◦and 30◦ among the patients admitted to icu. this study was conducted on 76 patients admitted to general icu, neurology icu and trauma wards of educational hospitals of rasht, iran, during 3 months. prior to the initiation of the study, approvals from the ethics committee of guilan university of medical sciences (ethics code: 290963812) and iranian registry of clinical trials (clinical trial number: irct201010214787n2) were secured. out of 289 patients evaluated in terms of inclusion criteria, the patients who met the criteria were enrolled in the study after obtaining consent from their legal guardian. 2.2. participants patients admitted to icu during the study period with age over 18 years, richmond agitation sedation scale (rass) score equal to -4 or -5, mechanically ventilated for at least 24 hours, lacking spinal cord damage, with normal intracranial pressure, without recent bladder surgery, and without both nasogastric tube and foley catheter, were included. exclusion criterion was intolerance to hob elevation, which didn’t occur during our study. 2.3. data gathering the research instrument was obtained from wsacs and consisted of three sections: the first section was dedicated to the personal characteristics of the patients, including age, gender, body mass index, disease diagnosis and the length of stay. the second section included sequential organ failure assessment (sofa) score, and the third section was related to iap measurement and recording, ventilator mode variables, mean arterial pressure (map), mean iap, mean airway pressure, maximum airway pressure, plateau pressure, abdominal perfusion pressure (app), and positive end-expiratory pressure measurement at 0◦, 15◦ and 30◦ head positions. sofa scores were calculated based upon the 24-hour period prior to the first iap measurement. 2.4. intervention iap measurement was performed through korn method using foley catheter (4, 13). after clamping the tube at the end of the collection bag, under sterile conditions, the aspiration port was connected to a short 18-g catheter with three stopcocks. they were connected to an intravenous infusion set, a syringe for flushing and draining the tube system, and a water manometer. zero reference was at the iliac crest in the mid-axillary line. twenty-five milliliters of saline were instilled into the bladder. three sets of iap measurement were done with hob angle elevated at 0◦, 15◦, and 30◦ every 8 hours during 24 hours (8am, 4pm, 12mn). the patients were followed during this period. all patients were flexed at the waist without readjustment of the manometer’s zero reference. iaps were measured at end-expiration with a minimum of 1 minute delay after patient positioning, for equilibration. iaps were measured in cmh2o and then converted into mmhg through multiplying by 0.74. the measurement of the bed angle was carried out by the index in the rail beside the bed based on the horizon level in each condition. to avoid technical errors, the same person carried out all of the measurements. after each measurement, the clamp was opened to discharge the normal saline from the patient’s bladder completely. also, the patient’s nurse was noted to subtracts the volume of the normal saline infused into the bladder from the total volume of urine drainage of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e23 the patient in that hour. by monitoring the patient’s ventilator, other pressure variables (like mean airway pressure, maximum airway pressure, etc.) were recorded. importantly, the duration of each measurement was about 7 to 8 minutes. the triplicate iap measurements for each body position were done. the iap was measured 228 times in each hob angle and 684 times in total. during the measurement, in the case of iah, the nurse or physician was called for treatment. in the present study, iap was an independent variable. iah (iap≥12 mmhg) was categorized as indicated below: grade i (12-15 mmhg), grade ii (16-20 mmhg), grade iii (21-25 mmhg), grade iv (>25 mmhg) (2). 2.5. statistical analysis the data were collected, encoded, and analyzed via descriptive and inferential statistics using the spss statistical software (v. 19). mean ± standard deviation (sd) was calculated for quantitative variables and frequency (%) for qualitative variables. kolmogorov smirnov test was utilized to check the normal distribution of data. all data were distributed normally. repeated measure analysis of variance (anova) and bonferroni post hoc tests were used to compare the mean abdominal pressure at different measurement angles. considering the insignificance of the mauchly test, sphericity and repeated measures anova tests were used to compare the trend and amount of iap changes with qualitative variables. to investigate the correlation of quantitative variables with mean iap, pearson test and fisher’s exact test were used. bland-altman analysis was performed to identify the bias and limits of agreement among the three positions. the wsacs states that a bias of <1 mm hg and limits of agreement between -4 and +4 are required for considering the two iap techniques equivalent (1, 19). p-value of <0.05 was considered statistically significant. 3. results 289 patients were evaluated, out of which 76 cases with the mean age of 50.31 ± 20.47 years met the predefined inclusion criteria and were enrolled in the study (72.4% male). the baseline characteristics of patients are presented in table 1. the iap was measured 228 times in each hob angle and 684 times in total. the prevalence of iah in the current study was 18.42%, and there was no case of abdominal compartment syndrome. the results showed that mean iap was 8.44 ± 4.02 mmhg in 0◦, 9.58 ± 4.52 mmhg in 15◦, and 11.10 ± 4.73 mmhg in 30◦ of hob (p < 0.001) (table 2). table 3 shows the prevalence of iah in three different hob degrees, 0◦, 15◦ and 30◦. normal iap prevalence was reduced from 0◦ (81.6%) to 15◦ (65.8%) and 30◦ (57.9%), and grade iii iah prevalence was increased from 0◦ to 30◦ (3.9%). in other words, with the increase in hob angle, iap was changed from a normal figure 1: the bias and agreement limit between intra-abdominal pressures (iaps) measured at 0◦ and 15◦ and 0◦ and 30◦ head of bed elevation. state to iah (p = 0.04). figure 1 shows the bias (1.13) and agreement limit (-2.67 to 4.94) between iaps measured at 0◦ and 15◦. figure 1 also indicates bias and agreement limit between iaps measured at 0◦ and 30◦ (the bias was 2.66 and the agreement limit was -1.66 to 6.89). 4. discussion the results showed that increase in hob angle from 0 to 30 degrees led to significant increase in iap and the prevalence of iah also increased from 0◦ to 30◦. in other words, by increasing hob angle, the normal iap turned in to iah. khalaf mahran et al. showed the significant mean iap changes between different hob elevations (hob angle 0◦, hob angle 15◦, and hob angle 30◦) (20). vasquez et al. found that iap changed from 10.2 mmhg at 0◦ to 12.4 mmhg at 15◦ and 14 mmhg at 30◦ (18). in another study, mcbeth et al. showed that with increase in hob, iap increased and this this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimian et al. 4 table 1: baseline characteristics of studied population (n = 76) variables values age (year) mean ± sd 50.31 ± 20.47 bmi (kg/m2) mean ± sd 23.70 ± 6.94 gender male 55 (72.4) female 21 (27.6) cause of admission trauma 46 (60.5) non-trauma 30 (39.47) mechanical ventilation modes simv 68 (89.5) bipap 2 (2.6) cpap 6 (7.9) length of stay (day) mean ± sd 5.43 ± 5.17 sofa score mean ± sd 6.85 ± 3.07 pressures mean arterial (mmhg) 95.15 ± 17.66 pip (cmh2o) 26.59 ± 6.93 plateau (cmh2 o) 17.05 ± 5.53 mean air way (cmh2 o) 9.67 ± 2.42 app (mmhg) 86.71 ± 1.65 iap at hob angle 0 (mmhg) 8.44 ± 4.02 iap at hob angle 15 (mmhg) 9.58 ± 4.52 iap at hob angle 30 (mmhg) 11.10 ± 4.73 data presented as mean ± standard deviation (sd) or number (%), bmi= body mass index, simv = synchronized intermittent mandatory ventilation, bipap= bi-level positive airway pressure, cpap= continuous positive airway pressure, hob: head of bed sofa= sequential organ failure assessment, pip= peak inspiratory pressure, iap= intra-abdominal pressure app= abdominal perfusion pressure. difference was significant when it changed from 30 degrees to 45 degrees (1). unlike the mentioned studies, cresswell et al. showed that the mean upper intra-abdominal pressure decreased by 2.1 mmhg when hob increased by 30◦. they explained that when the hob was elevated, the wall of the abdominal muscles relaxed and the abdominal wall tension decreased (21). another reason can be the pressure of organs on the abdomen due to the gravity force resulting from the change of body position (2). although measuring iap at 0◦ can predispose the patients to pneumonia and some other side effects, the iaps measured at 0◦, 15◦ and 30◦ cannot be considered precisely equal. so, if a decision needs to be made for patients’ treatment and management based on the measured iap at hob angles other than 0◦, these differences should be noticed. the changes of iap between 0◦, 15◦and 30◦ hob angles had a significant correlation with the age and the differences between iaps increase by age. murcia-saez et al. also found a significant correlation between the age and mean iap in their study participants (p=0.001, r=0.36) (10). ejike et al., in a study among the age group below 18 years old, found a significant correlation between the age and iap (p = 0.02) (12). but the study by vasquez et al. showed no correlation between the age and iap (p=0.3) (18). it can be said that the prevalence of comorbidities is higher in older age and the comorbidities themselves can increase iap. therefore, the difference in the results of different studies, mentioned previously, may be due the differences in participants and measurement techniques. bmi was considered an effective factor in our study, and it was significantly associated with iap (p=0.007). vasquez et al., in their study, showed that there was a significant correlation between bmi and mean iap. they found that bmi was in charge of 25-36% of the changes in iap (18). blaser et al. and mcbeth et al. also found the correlation between these two variables to be significant (p=0.01) (1, 22). it seems that the fat tissue in the abdominal cavity (central obesity) increased iap among people with high bmi by a direct effect on abdominal cavity and the bottom of pelvis (23). there was a significant correlation between the changes of iap and disease diagnosis (p=0.04) as the change increased among non-trauma patients compared to trauma patients. in a study by mcbeth et al., it was shown that iap and the diagnosis of neurologic disease had a significant correlation (p=0.001). in contrast, in surgical and trauma patients, no significant correlation was observed (1). in the epidemiological multi-centered study by malbrain et al., there was no significant correlation between the diagnosis of medical and surgical diseases with iap (24). moreover, ejik et al. also concluded that there was no significant correlation between disease diagnosis and iap changes in patients below 18 years old (12). however, in another study, which was done by murcia saez et al., the mean iap was high among surgical patients (p=0.001) (10). based on the distribution of disease diagnosis in our study, the studied patients were divided into two groups of trauma and non-trauma patients. various studies revealed different results about the correlation of iap and disease diagnosis. this may be due to the difference in categories of disease diagnosis. therefore, it seems that more studies are needed in the future in various groups of patients in terms of disease type. there was a significant correlation between the iaps at 0◦, 15◦ and 30◦ with various respiratory pressures, mean airway pressure, plateau pressure and positive end-expiratory pressure (p=0.05). the mean arterial pressure and iap also significantly correlated with each other at the three angles (p=0.0001). the rib cage and abdominal cavity are connected via diaphragm as averagely, 50% (25 to 80%) of the pressure of these two sections (abdomen and ribcage) are transferred to each other. with increase in iap, the diaphragm is elevated this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e23 table 2: comparison of mean intra-abdominal pressure (iap) at 0, 15 and 30 degrees of bed head angle and different measurement times times# head of bed angle (degree) p value 0◦ 15◦ 30◦ 0◦/15◦/30◦ 0◦/15◦ 0◦/30◦ 15◦/30◦ first 8.49± 4.27 9.61 ± 4.60 11.04 ±4.70 0.001 0.001 0.001 0.001 second 8.26 ± 4.16 9.52 ± 4.44 11.10 ± 4.71 0.001 0.001 0.001 0.001 third 8.57 ±4.14 9.60 ± 4.54 11.15 ± 4.79 0.001 0.001 0.001 0.001 *mean 8.44 ± 4.02 9.58 ± 4.52 11.10 ±4.73 0.001 0.001 0.001 0.001 data are presented as mean ± standard deviation; *mean iap in 24 hours; # times of measurement (the iap was measured 3 times in each degree of head of bed angle). table 3: intra-abdominal pressure changes at 0◦, 15◦ and 30◦ of head of bed angle based on grades of intra-abdominal hypertension angle# normal grade i grade ii grade iii grade iv total p* 0◦ 62 (81.6) 12 (15.8) 2 (2.6) 0 (0) 0 (0) 76 (100) 15◦ 50 (65.8) 20 (26.3) 5 (6.6) 1 (1.3) 0 (0) 76 (100) 0.04 30◦ 44 (57.9) 22 (28.9) 7 (9.2) 3 (3.9) 0 (0) 76 (100) data are presented as number (%). * fisher’s exact test; # the angle of head bed elevation. and leads to the compression of lungs and increase in the pressure of ribcage. following the rise in the pressure of the ribcage, increase in mean airway pressure, maximum airway pressure, plateau pressure, and positive end-expiratory pressure are expected. with an increase in ribcage pressure, the heart function and mean arterial pressure are also reduced. eventually, these events lead to the increase of iap(25, 26). based on the comparison of the bias and agreement limit of the measured values between 0◦ and 15◦ (1.13, -2.67 to +4.94), and between 0◦ and 30◦ (2.66, -1.66 to 6.89) with bias and agreement limit (-4 to +4) suggested by the wsacs, it was shown that the bias at 15 degrees compared to 0◦ (standard position) was closer to the required bias. the lower limit of the agreement in both 15◦and 30o compared to 0◦ (standard position) were approximately equal. however, the upper limits of agreement in both angles were higher than the wsacs upper limit, and the limit was much more near to the wsacs limit at 15◦. it was found that 87.6% of the agreement limit obtained between 0◦and 15◦ in this study was in the range proposed by the wsacs, and only about 13% was out of this limit and about the limits obtained between 0◦ and 30◦, 66.19% of the agreement limit obtained was in the range and 33.81% was out. in the study by cheatham et al., it was shown that the bias between 0 and 15 degrees was 1.5 mmhg, and the agreement limit was -2.8 to 5.8 and the bias between 0 and 30 degrees was 3.7 mmhg ,and the agreement limit was -2.2 to 9.6 (2). according to the results of previous studies, as also found in our study, an increase in hob will lead to a clinically important increase in iap. moreover, it can be concluded that iap at 15◦, in comparison to 30◦, can be considered more equal to iap at standard position. so considering hob seems to be important in interpretation of iap. the elevation of hob significantly increased iap. although iap needs to be measured for the patients admitted to icu, putting the patient at zero degree is not possible in some conditions because it led to signs of intolerance to the position and unavoidable complications among the patients. the results of our study showed that 87.6% of iaps measured at 15◦ were in the agreement limit in accordance with the wsacs. the hob angle in icus is often recommended to be adjusted to 30 degrees. it seems that measuring iap at 15◦ hob angle is more reliable than 30◦ in icu patients who cannot tolerate supine position. to determine the appropriate hob angle to measure iap in icu patients, further studies are needed to reveal any other factors that may affects iap, besides hob. there is also the need to evaluate whether the increase in hob leads to an equal increase in the iaps of four quadrants of the abdomen cavity or not. as long as more extensive studies evaluating the effects of position on iap aren’t available, it’s better to measure iap at 0◦ or standard position. 5. limitation one of the limitations of our study was lack of a special kit for measuring the iap. also, the patients who would not endure an elevation in hob were excluded in our study. unfortunately, many of these patients were at high risk for iah/acs. one of the positive aspects in our study is the evaluation of a larger sample size. according to the wsacs website, the minimum sample size for research on the iap measurement methods is 20 cases. 6. conclusion elevation of hob angle from 0 to 30 degree significantly increases iap. it seems that the measurement of iap at hob anthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. samimian et al. 6 gle 15◦ was more reliable than 30◦. 7. declarations 7.1. acknowledgment our gratitude goes to the research deputy of guilan university of medical sciences that approved this study and financially supported it and also to clinical research development unit of poursina hospital and all the people who helped us in this study. 7.2. authors’ contributions sedigheh samimian, tahereh khaleghdoost mohammadi, mohammad reza yeganeh and ali ashraf designed the study and analyzed the data. hamideh hakimi and maryam dehghani gathered and interpreted the data. sadra ashrafi, sedigheh samimian and maryam dehghani wrote the whole manuscript and sadra ashrafi also revised it carefully. all authors confirmed the final edited version of the manuscript. 7.3. conflict of interest the authors declare that they have no conflict of interest. 7.4. funding and supports this study was financially supported by research deputy of guilan university of medical sciences, rasht, iran (grant number: 290963812). references 1. mcbeth pb, zygun da, widder s, cheatham m, zengerink i, glowa j, et al. effect of patient positioning on intra-abdominal pressure monitoring. the american journal of surgery. 2007;193(5):644-7. 2. cheatham ml, de waele jj, de laet i, de keulenaer b, widder s, kirkpatrick aw, et al. the impact of body position on intra-abdominal pressure measurement: a multicenter analysis. critical care medicine. 2009;37(7):218790. 3. roberts dj, ball cg, kirkpatrick aw. increased pressure within the abdominal compartment: intra-abdominal hypertension and the abdominal compartment syndrome. current opinion in critical care. 2016;22(2):17485. 4. kirkpatrick aw, roberts dj, de waele j, jaeschke r, malbrain ml, de keulenaer b, et al. intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from 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bladder pressure measurements: an observational study. annals of intensive care. 2012;2(s1):s13. 18. vasquez dg, berg-copas gm, wetta-hall r. influence of semi-recumbent position on intra-abdominal pressure as measured by bladder pressure. journal of surgical research. 2007;139(2):280-5. 19. society tac. intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the world society of the abdominal compartment syndrome 2013 [available from: https://www.wsacs.org/images/2013%20guidelines%20 slide%20set.pdf. 20. mahran gsk, abd-elshafy sk, abd el neem mm, sayed ja. the effect of reference position versus right lateral position on the intra-abdominal pressure in mechanically ventilated patients. journal of nursing education and practice. 2018;8(6). 21. cresswell ab, jassem w, srinivasan p, prachalias aa, sizer e, burnal w, et al. the effect of body position on compartmental intra-abdominal pressure following liver transplantation. annals of intensive care. 2012;2(s1):s12. 22. blaser ar, regli a, de keulenaer b, kimball ej, starkopf l, davis wa, et al. incidence, risk factors, and outcomes of intra-abdominal hypertension in critically ill patients—a prospective multicenter study (iroi study). critical care medicine. 2019;47(4):535-42. 23. de keulenaer b, de waele j, powell b, malbrain m. what is normal intra-abdominal pressure and how is it affected by positioning, body mass and positive end-expiratory pressure? intensive care medicine. 2009;35(6):969-76. 24. malbrain ml, cheatham ml, kirkpatrick a, sugrue m, parr m, de waele j, et al. results from the international conference of experts on intra-abdominal hypertension and abdominal compartment syndrome. i. definitions. intensive care medicine. 2006;32(11):1722-32. 25. regli a, pelosi p, malbrain ml. ventilation in patients with intra-abdominal hypertension: what every critical care physician needs to know. annals of intensive care. 2019;9(1):52. 26. krebs j, pelosi p, tsagogiorgas c, alb m, luecke t. effects of positive end-expiratory pressure on respiratory function and hemodynamics in patients with acute respiratory failure with and without intra-abdominal hypertension: a pilot study. critical care. 2009;13(5):r160. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e53 or i g i n a l re s e a rc h comparison of emergency echocardiographic results between cardiologists and an emergency medicine resident in acute coronary syndrome fatemeh rasooli1, farideh bagheri 2, azadeh sadatnaseri 3, haleh ashraf3, maryam bahreini 1,4∗ 1. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 2. emergency medicine department, tehran university of medical sciences, tehran, iran. 3. cardiology department, sina hospital, tehran university of medical sciences, tehran, iran. 4. emergency medicine department, sina hospital, tehran university of medical sciences, tehran, iran. received: may 2021; accepted: june 2021; published online: 27 july 2021 abstract: introduction: early detection of regional wall motion abnormality (rwma) can be a reliable tool for rapid disposition of patients with acute coronary syndrome (acs) in the emergency department. in this study, the diagnostic accuracy of point-of-care echocardiography performed by a trained emergency medicine resident was evaluated in comparison with board-certified cardiologists. methods: a prospective, cross-sectional study was implemented on adult patients with acs. a trained emergency medicine (em) pgy-3 resident performed pointof-care echocardiography under the supervision of two cardiologists and the reports were compared with cardiologists as a reference test. results: 100 patients with the mean age of 54.1 ± 11.5 years were recruited (65% male). based on thrombolysis in myocardial infarction (timi) and history, ekg, age, risk factors, and troponin (heart) scores, 43.0% and 25.0% of patients were categorized as low-risk for acs, respectively. the absolute measure of agreement between cardiologists to determine ejection fraction (ef) was 0.829 (95% ci: 0.74-0.89) based on intraclass correlation coefficient (icc) estimation. the measurements of agreement between specialists and the em resident based on the analysis of kappa coefficient were 0.677 and 0.884 for rwma and pericardial effusion, respectively. moreover, 25 patients were in the-low risk group according to the heart score with an agreement rate of 92% for the lack of rwma between the em resident and cardiologists. conclusion: this study found acceptable agreement between the em resident and cardiologists in assessing rwma in different acs risk groups. in addition, there was acceptable agreement between the em resident and cardiologists in determining left ventricular ejection fraction (lvef) and pericardial effusion. keywords: emergency medicine; cardiologists; patient discharge; ultrasonography; point-of-care systems cite this article as: rasooli f, bagheri f, sadatnaseri a, ashraf h, bahreini m. comparison of emergency echocardiographic results between cardiologists and an emergency medicine resident in acute coronary syndrome . arch acad emerg med. 2021; 9(1): e53. https://doi.org/10.22037/aaem.v9i1.1247. 1. introduction it is crucial to manage the large number of patients who present to emergency departments (eds) with acute chest pain with utmost accuracy. traditionally, medical history, physical examination, electrocardiography, and chest radiography have been used in ∗corresponding author: maryam bahreini; emergency department, sina hospital, imam-khomeini ave., tehran, iran. e-mail: bahreinimaryam@gmail.com; m-bahreini@tums.ac.ir, tel/fax: +98-21-66348553, postal code: 1136746911, orcid: https://orcid.org/0000-0002-7655-0987. the emergency ward for screening patients with cardiovascular complaints (1). however, these diagnostic tools are not completely accurate for exact disposition of those with acute coronary syndrome (acs), especially in the low-risk group. focused cardiac ultrasound (focus) has become a vital tool in the evaluation of acs patients (2), as suggested by the american society of echocardiography (ase) and the american college of emergency physicians (acep) (3). it is a bedside, readily available, and noninvasive tool for real-time assessment of left ventricular ejection fraction (lvef), intravascular volume, pericardial effusion, and assessment of regional wall motion abnormality (rwma), as well as carthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rasooli et al. 2 diac activity in patients with pulseless electrical activity (47). echocardiography is considered a highly reliable modality to identify rwma (8). abnormal left ventricular wall motion can suggest a significant coronary artery obstruction. the sensitivity of transthoracic echocardiography alone for suspecting myocardial ischemia was found to be 91 percent for acs disposition in low-risk patients. also, early normal echocardiogram in suspected patients in the ed indicates a lower clinical risk (8). cardiologists routinely perform full standard transthoracic echocardiography (tte) to manage acs patients; however, they do not usually work full-time and are not always available in eds. as a result of the delay in the disposition of acs patients, emergency rooms become more crowded, which has financial consequences for both patients and hospitals. on the other hand, emergency medicine (em) specialists constantly reside in eds and are familiar with applying point-of-care ultrasound in emergency situations. the aim of this study was to assess the diagnostic accuracy of pointof-care echocardiography performed by a trained emergency medicine resident in comparison with board-certified cardiologists. 2. methods 2.1. study design and setting this is a prospective, cross-sectional study on adult patients (≤18 years-old) with acute coronary syndrome presenting to the eds of two referral university hospitals with 50000-75000 annual visits from 2018 to 2019. the ethical aspects of this study were approved by tehran university of medical sciences institutional review board (ethics code: ir.tums.vcr.rec.1398.144). informed consent was taken from all patients after complete explanation of the study. 2.2. participants patients with st segment elevation myocardial infarction (mi) who needed primary coronary intervention (pci) and participants with pacemaker implantation were excluded because of their influence on estimating cardiac wall motion. 2.3. data gathering and procedure data were recruited by an emergency medicine resident of postgraduate residency year (pgy)-3 as well as the cardiologists who were present in the hospitals to give cardiology consults in different days of the week in the morning and evening shifts. according to the routine protocol, patients are emergently visited by emergency medicine residents, stabilized, and then visited by internal medicine residents by request for cardiology visits. except for very low-risk acs patients who are discharged, others stay in the emergency ward to undergo further testing for final disposition. data were collected via convenient sampling. the em resident initially spent a 2hour theoretical course emphasizing on quantitative ejection fraction (ef) estimation, presence of pericardial effusion, and rwma assessment, then passed a 20-hour handson training course under the supervision of the two cardiologists according to the emergency ultrasound guidelines of acep (1). the echocardiographs were performed using the ultrasound machines ge vivid e9 and samsung ugeo hm70a using phased-array 2-4 mhz transducers. visual estimation was performed for the assessment of left ventricular function (lvf) both qualitatively and quantitatively, and focused ultrasound views were performed, including parasternal long axis, parasternal short axis, apical 4-chamber and subcostal views. the lvf according to the lvef was categorized as normal (lvef >55%), mild to moderate dysfunction (lvef 35-55%), and severe dysfunction (lvef<35%) (9). patients were assessed to determine whether they had rwma or not. rwma was assessed in four views including long axis, short axis, apical 4-chamber and two chamber views. akinesia, hypokinesia and dyskinesia of left ventricle were considered as rwma that can be detected immediately after an ischemic event preceding ecg and biomarker alternations (8). besides, increased echogenicity, decreased thickness, and evidence of remodeling such as dyskinesia, as chronic ischemic changes, were evaluated. the sub-xiphoid view was also used to assess pericardial effusion. the study was performed in two phases. echocardiography was first implemented by the emergency medicine resident, then by either cardiologist, who was blind to the resident’s results, at most 1 hour apart. echocardiogram findings were documented along with other information such as history, ekg, age, risk factors, and troponin (heart) and thrombolysis in myocardial infarction (timi) scores in the questionnaire. the clinical decisions and interventions were performed according to the risk stratification of heart score and based on the cardiologists’ decisions for moderate-risk patients. patients with regional wall motion abnormality on focus were admitted for further assessment. acute coronary syndrome was defined as acute chest pain, dyspnea, or weakness, and also syncope with a cardiac cause. 2.4. outcomes first, the agreement between the em resident and cardiologists was analyzed in assessment of cardiac function (rwma, lvef, and pericardial effusion) using point-of-care ultrasound in acs. the examination results of the board-certified cardiologists were considered as gold standard. the results were also sub-analyzed based on the risk stratification of patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e53 figure 1: the bland-altman plot of ejection fraction (ef) which shows the agreement between the em resident and cardiologists. 2.5. statistical analysis based on a previous study, the kappa coefficient of agreement between em specialists and cardiologists in evaluation of cardiac function was considered 0.71; with a confidence interval of 95% and a margin of error of 5%, a sample size of 88 patients was required (nquery advisor). adding 10% to adjust for potential missing data, the final total sample size was about 100. the mean differences of ef between the emergency medicine resident and the cardiologists were assessed using independent t-test. furthermore, the bland-altman plot was used to measure the agreement between the two specialists. to construct a bland-altman plot, the difference between ef measured by specialists was plotted on the y-axis against the average of the total amount on the x-axis. moreover, the intra-class correlation coefficient (icc) was analyzed to assess the agreement on ef estimation. the specialists’ agreement on rwma and pericardial effusion was assessed by measuring kappa coefficient. in addition, the performance accuracy of the em resident in determining rwma was assessed in comparison with board-certified cardiologists as the gold-standard. thus, we used receiver operating characteristic (roc) curve analysis and calculated sensitivity, specificity, and negative and positive predictive values with 95% confidence interval. the statistical uncertainty of calculated statistics was shown by 95% confidence interval. the level of significance was 0.05. data were analyzed using stata and medcalc softwares. 3. results 3.1. baseline characteristics of studied cases in this study, 100 patients with the mean age of 54.1 ± 11.5 (24-84) years were recruited (65.0% male). of whom, 26.0% table 1: baseline characteristics of studied cases variable value age (year) 54.1 ± 11.5 gender male 65 (65.0) female 35 (35.0) vital signs systolic blood pressure (mmhg) 136.2 ± 16.4 diastolic blood pressure (mmhg) 81.6 ± 9.0 pulse rate (bpm) 75.3 ± 10.6 respiratory rate (bpm) 13.1 ± 1.6 saturation o2 93.7 ± 2.5 medical history angiography 26 (26.0) cabg 9 (9.0) asa use 50 (50.0) hypertension 49 (49.0) diabetes mellitus 19 (19.0) hyperlipidemia 33 (33.0) cigarette smoking 40 (40.0) troponin i abnormal 22 (22.0) ecg changes not visible 8 (8.0) not noticeable 59 (59.0) clinically significant 33 (33.0) timi score low risk 43 (43.0) moderate risk 47 (47.0) high risk 10 (10.0) heart score low risk 25 (25.0) moderate risk 54 (54.0) high risk 21 (21.0) data are presented as mean ± standard deviation or number (%). sd: standard deviation; cabg: coronary artery bypass graft; asa: acetylsalicylic acid; ecg: electrocardiogram; cabg: coronary artery bypass graft; asa: acetylsalicylic acid; ecg: electrocardiogram. and 9.0% had a positive history of coronary angiography (cag) and coronary artery bypass graft (cabg), respectively. based-on the timi and heart scores, 43.0% and 25.0% of patients were categorized as low-risk, respectively. table 1 depicts the distribution of demographics, clinical presentations, vital signs, past history, and risk factors of patients at the time of admission. 3.2. echocardiographic findings ef the mean ejection fraction determined by cardiologists and the emergency medicine resident was 50.7 ± 4.8 vs. 49.8 ± 5.2 percent, respectively (p=0.001). figure 1 presents the blandaltman plot of ejection fraction (ef) between the em resident and cardiologists. the absolute measure of agreement between specialists for ef estimation was 0.829 (95% ci: 0.74this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rasooli et al. 4 table 2: agreement and accuracy indices of regional wall motion abnormality (rwma) and pricardial effusion between cardiologist (goldstandard) and emergency medicine (em) resident cardiologists kappa accuracy sesitivity spesificity auc ppv npv p n rwma in total em p 29 9 0.677 85.0% 82.9 (66.4,93.4) 86.2 (75.3,93.5) 0.85 (0.76,0.91) 76.3 (59.8,88.6) 90.3 (80.1,96.4) resident n 6 56 pricardial effusion em p 4 0 0.884 99.0% 80.0 (28.4,99.5) 100 (96.2, 100) 0.90 (0.82,0.95) 100 (39.8, 100) 99.0 (94.3, 100) resident n 1 95 rwma without patients with prior angiography or cabg em p 15 7 0.682 85.0% 88.2 (63.6,98.5) 86.8 (74.7,94.5) 0.88 (0.77,0.94) 68.2 (45.1,86.1) 95.8 (85.7, 9.5) resident n 2 46 data are presented with 95% confidence interval. p: positive; n: negative in retest; ci: confidence interval; auc: area under the curve; ppv: positive predictive values; npv: negative predictive values; cabg: coronary artery bypass graft. 0.89) based-on intraclass correlation coefficient (icc). we also analysed data after removing patients with a history of cag or cabg. the mean ef determined by cardiologists in comparison with emergency medicine specialists was 51.9 ± 4.6 vs. 50.6 ± 5.2 percent, respectively (p=0.001). the absolute agreement of specialists for determining ef was 0.897 (95% ci: 0.80-0.94) based on intraclass correlation coefficient (icc). 3.3. rwma and pericardial effusion the agreement rates between specialists and the em resident based on analysing kappa coefficient were 0.677 and 0.884 for rwma and pericardial effusion, respectively. furthermore, the performance of em resident had the sensitivity and specificity of 82.9% and 86.2% for rwma estimation and 80.0 and 100% for detecting pericardial effusion, respectively. from all low-risk patients according to the timi score (43 patients), 35 and 40 individuals were reported to have no rwma by the em resident and cardiologists on echocardiography, respectively. thus, the agreement between them was 81.3%. moreover, 25 patients were in the low-risk group according to the heart score; of whom, 23 and 25 patients had normal wall motion according to the report of the em resident and cardiologists, respectively. therefore, the agreement between them was 92%. 3.4. screening performance characteristics of echocardiography by em resident table 2, presents acuracy indices and predictive values in estimation of rwma and pricardial effusion by the em resident. 4. discussion in our study, there was a moderate agreement between the em resident and cardiologists with an acceptable accuracy. the specificity and negative predictive value of the echocardiograms of the em resident improved when eliminating patients with a history of cag or cabg. we found that the agreement on rwma estimation was higher in low-risk patients according to the heart score risk stratification in comparison with the timi score. furthermore, the absolute agreement on ef estimation was acceptable. emergency medicine specialists make critical decisions in a short time period, mandating goal-directed and focused point-of-care ultrasound in many circumstances. regarding benefits and harms, the determination of ef and rwma using focus are important in low-risk patients with acs to make more accurate dispositions and to reduce the possibility of unpredictable major cardiac events (1) in conjunction with risk stratification tools such as heart/timi score. considering the harmlessness of bedside ultrasound and the applicability of this module, it can be performed frequently in eds. previous studies have administered several training modules, which varied in duration and major outcomes. in monsomboon’s study, em residents passed a 3-hour echocardiography training course focusing on lvef visual estimation (10) and other researchers mentioned 4 to 6 hours of video programs (11-13). furthermore, some aimed at training residents of em or intensive care to get familiar with standard cardiac views within 3 to 12 hours (14, 15). in a study by kerwin et al. trainees were capable of interpreting echocardiographic abnormalities with significant improvement after a 30-minute training period (16). overall, these studies confirmed the trainees’ capabilities to perform echocardiography in comparison with cardiologists after the mentioned training time. 4.1. assessment of rwma the detection of rwma by em residents is very helpful in patients’ disposition. a small number of studies have evaluated the reliability of em residents’ scans and few have asthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e53 sessed their agreement with cardiologists. the probability of coronary artery disease (cad) increases with new rwmas in patients with acute chest pain (17). on the other hand, the absence of rwma in patients with acs can lead to a safer discharge in conjunction with being categorized as low-risk based on a risk stratification tool. as mentioned in arntfield’s study, 98% of suspected cad patients with no rwma had a negative work-up for cad (6). in our study, there was moderate agreement (0.677) between the em resident and cardiologists with an accuracy of 85%. the specificity and negative predictive values of the echocardiograms by the em resident were 86.2% and 90.3%, which improved by eliminating patients with history of cag or cabg. farsi et al. showed 92% agreement on rwma between cardiologists and em residents. interestingly, the specificity and negative predictive value of echocardiograms performed by the em resident were 87% and 98%, which are very close to our findings (13). we found that the agreement on rwma estimation was higher in patients who were low-risk according to the heart score in comparison with the timi score. thus, we propose using the combination of the heart score with rwm status to speed up disposition of acs patients from the emergency ward. in this regard, emergency specialists can more safely discharge low-risk patients with normal regional wall motion. 4.2. ef assessment in this study, the mean ef measured by cardiologists was significantly higher than the em resident (p=0.001), yet this difference was not considered clinically significant. the absolute agreement on ef estimation was 0.829 based on the interclass correlation coefficient (icc), which presents an acceptable reliability. eliminating patients with a history of cag or cabg, the agreement reached 0.897, which may reflect better evaluation of lvef by the em resident in less complicated patients. in this regard, the agreement between the em resident and the cardiologist on estimating ventricular function was 79.4% in monsomboon’s study (10). also moore and et al. showed weighted agreement of 84% between emergency physicians (eps) and cardiologists with a weighted kappa of 0.61 (p < 0.001) in quantitative visual estimation of lvef (12). in other studies, the agreement between trainees and cardiologists were considered acceptable with fair accuracy for lvef estimation after minimal training (12, 14, 18-20). in a study by bustam et al., the agreement between trainees and the cardiologist was 93% for visual estimation and 92.9 % for quantitative evaluation of lvef and the bland– altman limits of agreement for lvef assessment were similar to our study (11). this agreement was 91% in farsi’s investigation (13). 4.3. assessment of pericardial effusion in this study, there was a desirable agreement between the em resident and cardiologists in determining pericardial effusion, which is similar to bustam’s study with a sensitivity, specificity, ppv and npv of 60, 100, 100 and 97.9 %, respectively (11). the accuracy of finding pericardial effusion by em residents was 99% in mandavia and monsomboon’s studies (10, 21). 5. limitations and suggestions it is worth assessing the inter-rater reliability of cardiologists, which can be further studied although we had similar institutional protocols to carry out measurements. on the other hand, increasing the number of operators mandates coordination and this issue can be addressed in further studies to improve generalizability. potential bias was reduced through cardiologists teaching echocardiographic measures. differentiating between new and old rmwa is considered challenging even for skilled em sonographers; thus, the em resident in this study detected every abnormality without spending time on differentiation between the old and new lesions. wall thickness measurements can differentiate old ischemia from a new one, which was not assessed in this study. on the other hand, the differential diagnoses of rwma could confuse the operator, which are worth addressing. applying a specific cardiac scoring system such as heart score in conjunction with point-of-care echocardiography can lead to a faster and safer disposition focusing on rwma in acs patients. patients who had a low risk of acs according to heart score with normal wall motion in echocardiography can have ambulatory follow-up for major cardiac events. 6. conclusion this study found acceptable agreement between the em resident and cardiologists in assessing rwma, which was also seen in low-risk patients. besides, there was acceptable agreement between the em resident and cardiologists in determining lvef and pericardial effusion. 7. declarations 7.1. acknowledgments we kindly thank dr. mehdi mehrani, md for his valuable cooperation in carrying out this study. 7.2. funding none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rasooli et al. 6 7.3. author contribution concept and design: fr, fb, mb, as, ha data collection: fb, as, ha writing the article: fr, mb, fb, as, ha critical revision of the article: fr, mb, as, ha, fb final approval of the article: fr, mb, as, ha, fb 7.4. conflict of interest none. references 1. frederiksen ca, juhl-olsen p, andersen nh, sloth e. assessment of cardiac pathology by point-of-care ultrasonography performed by a novice examiner is comparable to the gold standard. scandinavian journal of trauma, resuscitation and emergency medicine. 2013;21(1):87. 2. rutz ma, clary jm, kline ja, russell fm. emergency physicians are able to detect right ventricular dilation with good agreement compared to cardiology. academic emergency medicine. 2017;24(7):867-74. 3. labovitz aj, noble ve, bierig m, goldstein sa, jones r, kort s, et 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echocardiography in the emergency department. australasian journal of ultrasound in medicine. 2019;22(1):6-11. 18. melamed r, sprenkle md, ulstad vk, herzog ca, leatherman jw. assessment of left ventricular function by intensivists using hand-held echocardiography. chest. 2009;135(6):1416-20. 19. pershad j, myers s, plouman c, rosson c, elam k, wan j, et al. bedside limited echocardiography by the emergency physician is accurate during evaluation of the critically ill patient. pediatrics. 2004;114(6):e667-e71. 20. jacob m, shokoohi h, moideen f, pousson a, boniface k. an echocardiography training program for improving the left ventricular function interpretation in emergency department; a brief report. emergency. 2017;5(1). 21. mandavia dp, hoffner rj, mahaney k, henderson so. bedside echocardiography by emergency physicians. annals of emergency medicine. 2001;38(4):377-82. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations and suggestions conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e48 or i g i n a l re s e a rc h risk factors of readmission in covid-19 patients; a retrospective 6-month cohort study mohammad haji aghajani1,2a, reza miri1,2a, mohammad sistanizad1,3, amirmohammad toloui4, arian madani neishaboori4, asma pourhoseingholi1, ziba asadpoordezaki5,6, roxana sadeghi1,2∗, mahmoud yousefifard4,7† 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of cardiology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 4. physiology research center, iran university of medical sciences, tehran, iran. 5. department of psychology, maynooth university, kildare, ireland. 6. kathleen lonsdale institute for human health research, maynooth university, kildare, ireland. 7. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: march 2022; accepted: may 2022; published online: 20 june 2022 abstract: introduction: the available literature regarding the rate of readmission of covid-19 patients after discharge is rather scarce. thus, the aim in the current study was to evaluate the readmission rate of covid-19 patients and the components affecting it, including clinical symptoms and relevant laboratory findings. methods: in this retrospective cohort study, covid-19 patients who were discharged from imam hossein hospital, tehran, iran, were followed for six months. data regarding their readmission status were collected through phone calls with covid-19 patients or their relatives, as well as hospital registry systems. eventually, the relationship between demographic and clinical characteristics and readmission rate was assessed. results: 614 patients were entered to the present study (mean age 58.7±27.2 years; 51.5% male). 53 patients were readmitted (8.6%), of which 47 patients (7.6%) had a readmission during the first 30 days after discharge. the reasons for readmission were relapse of covid-19 symptoms and its pulmonary complications in 40 patients (6.5%), covid-19 related cardiovascular complications in eight patients (1.3%), and non-covid-19 related causes in five patients (0.8%). older age (or=1.04; 95% ci: 1.01, 1.06; p=0.002) and increased mean arterial pressure during the first admission (or=1.04; 95% ci: 1.01, 1.08; p=0.022) were found to be independent prognostic factors for the readmission of covid-19 patients. conclusion: readmission is relatively frequent in covid-19 patients. lack of adequate hospital space may be the reason behind the early discharge of covid-19 patients. hence, to reduce readmission rate, extra care should be directed towards the discharge of older or hypertensive patients. keywords: patient readmission; prognosis; follow-up studies; covid-19 cite this article as: haji aghajani m, miri r, sistanizad m, toloui a, madani neishaboori a, pourhoseingholi a, asadpoordezaki z, sadeghi r, yousefifard m. risk factors of readmission in covid-19 patients; a retrospective 6-month cohort study. arch acad emerg med. 2022; 10(1): e48. https://doi.org/10.22037/aaem.v10i1.1514. ∗corresponding author: associate professor, imam hossein hospital, madani st., tehran, iran; phone/fax: +982173432383/77582733; e-mail: roxan.sadeghi@sbmu.ac.ir, orcid: http://orcid.org/0000-0001-9447-8483. † corresponding author: mahmoud yousefifard; physiology research center, school of medicine, iran university of medical sciences, shahid hemmat highway, tehran 14496-14535, iran. tel: +98 (21) 86704771; email: yousefifard.m@iums.ac.ir, orcid: http://orcid.org/0000-0001-5181-4985. a, first and second authors have same contribution. 1. introduction since december 2019 and the emergence of the “severe acute respiratory syndrome coronavirus 2”, a novel virus from the family of coronaviruses, in wuhan, china, until january 29, 2021, more than 102 million people have been infected, worldwide, and over 2.2 million people have died due to the disease caused by it. world health organization (who) has named the disease covid-19, and its pandemic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 2 continues to this day (1, 2). the most common organs involved in this disease are the lungs, and the most prevalent clinical signs are fever, cough, body aches, fatigue, and shortness of breath. however, signs of the involvement of other organs, such as neurological, cardiovascular and renal signs, have also been reported (3, 4). the incidence of severe clinical signs and the severe form of the disease is higher in older people and patients with an underlying disease, compared to other patients. death is also more frequent in these people. hypertension due to diabetes and cardiovascular diseases have been reported to be the most common underlying diseases corresponding to disease severity and mortality due to covid-19 (5-8). considering the increasing number of covid-19 patients, worldwide, the shortage in the number hospital beds and the crushing pressure on the health care systems are becoming a global crisis. in these circumstances, doctors may be prompted into early discharge of the patients, which could cause readmission of the discharged patients and eventually increase the pressure on the health care systems, even more. moreover, several studies exist that have reported cases of readmission among covid-19 patients (9, 10). on that account, knowing the exact probability of readmission due to covid-19 and the factors affecting it would be of great importance in aiding patients’ management and anticipating the treatment results. the most important reasons for readmission in covid-19 patients are the reoccurrence of respiratory symptoms or the occurrence of non-pulmonary complications of covid-19, such as cardiovascular, central nervous system, and renal complications. in this regard, few studies exist, reporting a readmission rate of two to 19 percent (11-14). this versatility in the reporting rates, in addition to the limited existing evidence, presents the need for further research in this field. since the probability of readmission due to covid-19 in the current crisis situation should be assessed precisely, our aim in the present study is to investigate the rate of readmission in covid-19 patients and the affecting factors, including clinical symptoms and related laboratory findings. 2. methods 2.1. study design and setting the present study is a retrospective cohort study, conducted on patients admitted to imam hossein hospital, tehran, iran, between february 18, 2020 and july 20, 2020. covid-19 infection was confirmed based on rt-pcr test. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences (code: ir.sbmu.retech.rec.1399.680), and the researchers adhered to the principles of helsinki declaration throughout the study. 2.2. participants in the present study, confirmed covid-19 patients admitted to imam hossein hospital, who were recovered from the disease and discharged, were recruited. exclusion criteria was insufficient clinical and laboratory data, patients’ death during the first admission, and not being able to contact the patient after discharge. 2.3. data gathering in the present study, data from all covid-19 patients, admitted to imam hossein hospital, were gathered through hospital registry databases. then, mortality cases were eliminated. next, based on their admission code and iranian national code, patients who were readmitted to imam hossein hospital were identified. the data extracted from patients’ records included demographic data, history of cardiovascular disease, history of other comorbidities, clinical symptoms at the time of admission, mean arterial pressure during their hospital stay, laboratory and imaging findings, and the patients’ status at the time of discharge. later on, a nurse, familiar with the data collecting process, contacted all the included patients through phone call, to ask about the readmission cases in other hospitals. in cases of no answer, a second call was made within 24 hours. if no one answered, other phone numbers in the patient’s hospital profile were reached. if again no one answered the call, another phone call was made, one week later, to minimize the missing data. it is worth to mention that the least follow up period was six months, whereas the longest follow up timeframe was nine months. also, the assessed outcome in our study was readmission. in the assessment of the underlying causes of readmission (either from the patients’ profile or phone call), the causes were divided into three groups: readmission due to the covid-19 disease or respiratory complications, readmission due to cardiovascular complications, and readmission due to other causes. readmission was defined as the rehospitalization of covid-19 patients who had previously recovered from covid-19 within 2 weeks after discharge (15). 2.4. statistical analysis all analyses were performed using spss 22.0 statistical program. quantitative data were presented as mean and standard deviation (sd) or median and interquartile range, and qualitative data were reported as frequency and percentage. patients were classified into two groups of readmission and non-readmission. next, the relationship of demographic characteristics and clinical symptoms or laboratory findings with readmission was investigated. for the comparison of quantitative variables, t-test or mann-whitney equivalent was used. also, for the comparison of qualitative variables, chi-square or fisher’s exact tests were applied. furthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e48 figure 1: flow diagram of the present study. thermore, the relationship between the confounding factors was assessed fitting a stepwise multivariate logistic regression model to investigate the relationship between demographic variables, clinical symptoms or laboratory findings and readmission. in all analyses, a p value less than 0.05 was considered significant. the prevalence of readmission was 19.9% in the study with the longest follow up design, which was two months of follow up (11). therefore, considering the 95% confidence interval (ci) and 5% error, the minimum required sample size was calculated to be 246 patients for the entire study. 3. results during the study period, data from 991 patients had become available. of these, 257 patients died during their hospitalization and 734 patients were discharged. throughout the follow up, 120 patients (16.3%) did not answer the phone call, so 614 patients entered the present study (figure 1). the mean age of these patients was 58.7±27.2 years and 51.5% of them were male. of these 614 patients, 53 patients were readmitted (8.6%), out of which 47 patients’ readmission (7.6%) had occurred within the first 30 days following their discharge. the median time frame between discharge and readmission was 6.5 days (with a range of 1 to 240 days). the reasons for readmission were relapse of covid-19 symptoms and its pulmonary complications in 40 patients (6.5%), covid-19 related cardiovascular complications in eight patients (1.3%), and non-covid-19 related causes in five patients (0.8%) (figure 2). univariate analyses showed that the mean age of the readmitted patients (66.6±16.5 years) was lower than the mean age of the non-readmitted group (57.9±16.5 years) (p<0.001). also, possible prognostic factors for the readmission of covid-19 patients in univariate analyses included a history of coronary artery diseases (p=0.013), mean arterial pressure during hospitalization (p=0.028), white blood cells count in the blood (p<0.001), lymphocyte count in the blood (p=0.004), neutrophil count in the blood (p=0.034), and the occurrence of cardiovascular accidents during hospitalization (p=0.041) (table 1 and 2). the multivariate logistic regression model depicted that older age (or=1.04; 95% ci: 1.01, 1.06; p=0.002) and increased mean arterial pressure during the first hospitalization (or=1.04; 95% ci: 1.01, 1.08; p=0.022) were independent prognostic factors for the readmission of covid-19 patients (table 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 4 table 1: baseline characteristics of covid-19 patients based on readmission status variable readmitted total (n=614) p no (n=561) yes (n=53) age (year) 57.9±16.5 66.6±16.5 58.7±27.2 <0.001 gender female 272 (48.5) 26 (49.1) 298 (48.5) 0.937 male 289 (51.5) 27 (50.9) 316 (51.5) bmi (kg/m2) —26.92±6.0 27.2±4.9 history of coronary artery disease no 408 (72.70) 30 (56.60) 438 (71.30) 0.013 yes 153 (27.30) 23 (43.40) 176 (28.70) length of stay —7.0±8.1 7.4±5.5 0.055 vital sign body temperature 37.0 (36.8, 37.3) 37.0 (36.9, 37.3) 37.0 (36.8, 37.3) 0.351 heart rate (beat/min) 83.3 (79.3, 89.0) 82.7 (78.8, 89.2) 83.3 (79.3, 89.0) 0.942 spo2 (%) 91.7 (89.7, 94.0) 91.3 (88.7, 93.8) 91.7 (89.7, 94.0) 0.393 respiratory rate (per min) 18.7 (17.3, 21.3) 19.3 (18.0, 22.7) 18.7 (17.7, 21.6) 0.104 mean arterial pressure (mmhg) 86.7 (81.1, 91.1) 90.0 (82.2, 95.0) 86.7 (81.1, 91.1) 0.028 laboratory pvo2 (mmhg) 29.0 (23.3, 39.7) 30.6 (22.7, 47.1) 29.2 (23.2, 40.1) 0.531 pvco2 (mmhg) 42.2 (37.6, 46.4) 41.7 (35.6, 45.8) 42.1 (37.5, 46.3) 0.445 wbc count 6.5 (4.9, 8.6) 8.1 (6.1, 11.7) 6.6 (5.0, 8.8) <0.001 lymphocyte (%) 20.0 (13.1, 27.0) 16.0 (10.3, 21.4) 20.0 (13.0, 26.7) 0.004 neutrophil (%) 73.1 (65.5, 80.0) 74.7 (69.5, 83.1) 73.3 (65.6, 80.3) 0.034 crp (mg/l) 45.1 (19.4, 72.0) 42.1 (18.6, 66.1) 44.6 (19.2, 72.0) 0.349 hb (gr/dl) 12.6 (11.4, 13.7) 12.2 (11.2, 13.3) 12.6 (11.4, 13.7) 0.334 rbc count 4.5 (4.1, 4.9) 4.5 (4.0, 4.8) 4.5 (4.1, 4.9) 0.646 cr (mg/dl) 1.1 (1.0, 1.4) 1.2 (1.0, 1.7) 1.2 (1.0, 1.4) 0.135 hematocrit (%) 37.5 (34.2, 40.5) 36.8 (33.9, 40.8) 37.5 (34.2, 40.5) 0.643 cpk (u/l) 104.0 (58.0, 222.5) 90.0 (55.8, 240.5) 103.0 (58.0, 222.0) 0.752 cardiac dysrhythmia no 264 (52.40) 24 (49.00) 288 (52.10) 0.649 yes 240 (47.60) 25 (51.00) 265 (47.90) cardiac complication during hospitalization no 527 (93.90) 45 (84.90) 572 (93.20) 0.041 yes 34 (6.10) 8 (15.10) 42 (6.80) data are presented as mean ± standard deviation, median (percentile 25percentile 75) and frequency (%). wbc: white blood cell; rbc: red blood cell; crp: c-reactive protein; hb: hemoglobin; cr: creatinine; cpk: creatine phosphokinase. table 2: comparing the readmission rate based on the covid-19 treatment protocol treatment protocol readmitted total (n=614) p no (n=561) yes (n=53) corticosteroid + interferon + remdesivir 10 (1.80) 1 (1.90) 11 (1.80) corticosteroid + interferon + favipiravir 13 (2.30) 0 (0.00) 13 (2.10) corticosteroid + interferon + kaletra + hcq 48 (8.60) 6 (11.30) 54 (8.80) corticosteroid + interferon + kaletra 32 (5.70) 0 (0.00) 32 (5.20) interferon + kaletra + hcq 42 (7.50) 5 (9.40) 47 (7.70) 0.290 interferon + kaletra 27 (4.80) 3 (5.70) 30 (4.90) kaletra + hcq 86 (15.30) 6 (11.30) 92 (15.00) hcq 163 (29.10) 12 (22.60) 175 (28.50) others 140 (25.00) 20 (37.70) 160 (26.10) data are presented as frequency (%). hcq: hydroxychloroquine. 4. discussion for the first time, the present study aimed to follow covid19 patients for a period of six months to conclude that 8.6% of the patients discharged alive will be admitted to the hospital, again. of these, 75.5% of the readmission cases were due to the recurrence of the covid-19 symptoms or its respirathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e48 table 3: multiple logistic regression for prediction of readmission of covid-19 patients variable odds ratio 95% ci p older age 1.04 (1.01, 1.06) 0.002 cardiac complication during hospitalization 2.32 (0.86, 6.25) 0.095 increase in lymphocyte (continuous) 0.96 (0.93, 1.00) 0.051 increase in mean arterial pressure (continuous) 1.04 (1.01, 1.08) 0.022 ci: confidence interval. tory complications, and cardiovascular complications were the cause in 15.1% of the readmitted patients. the most paramount prognostic factors for readmission were older age and increased mean arterial pressure during the first hospital stay. the findings of the current study demonstrated that 67.9% of the readmissions occur during the first week following discharge. hence, it seems that the impetuosity of health care directors in patients’ discharge could have been the primary reason behind the readmissions. this matter can be attributed to the lack in the resources, such as hospital beds, human resources, and equipment, during the peak of the pandemic, which could have been the leading cause behind the early discharge of the patients, showing relative resolution of their symptoms without complete recovery or having a negative pcr test. as a result, the primary cause of the readmissions should be considered the lack of resources, rather than medical errors. as shown in preceding studies, a great number of covid-19 patients develop cardiovascular complications (16). therefore, 15.1% of the readmission cases may be related to the cardiovascular complications following covid-19. since we showed that a history of cardiovascular comorbidities was unrelated to readmission, the cardiovascular complications that led to readmission may be due to the infection itself. the available evidence indicate that older age is an independent factor for the severity of the disease and its pertaining mortality (5, 6, 17, 18). in the present study, it was depicted that age is an independent risk factor for the readmission of covid-19 patients as well, indicating the role of older age in the development of severe clinical symptoms and prolonged course of the disease. on the contrary, donnelly et al., who performed a two-month follow up on covid-19 patients and presented a 19.9% readmission rate, did not find a relationship between older age and readmission (11). this difference between the results of the present study and that of donnelly et al.’s may be because of the differences between the ages of the included patients. in the current study, 22.4% of the patients were under 45 years old, while in that study, only 3.2% of the patients were under 45 years of age. since donnelly et al.’s study was conducted in a much narrower range of age and their patients group consisted of a larger group of old patients, their nonsignificant results for the relationship of readmission and older age may be attributed to these two reasons. in another study by yeo et al. the 30-day readmission rate of covid-19 patients was evaluated (14). in this study, it was concluded that 4.5% of the patients may be readmitted during the mentioned timeframe. meanwhile, this rate was calculated to be 8.6% in the present study. this difference between the two rates may be attributed to the follow up strategy adopted in their study and that of ours. in yeo et al ‘s study, the follow up timeframe was decided to be 30 days, while in our study this timeframe was six months. more importantly, in yeo et al.’s study, readmission to other hospitals was not assessed. in other words, readmissions to a single center was evaluated in their study. consequently, the actual rate of readmission may be underestimated in their study, because a number of the patients may be admitted to other hospitals. in the present study, this bias was prevented by contacting the patients or their relatives through phone calls, in addition to reviewing profiles of patients who were readmitted to imam hossein hospital, to include readmissions to other medical centers, as well. in addition, there are studies reporting a readmission rate of about 2% for covid-19. however, their results were limited to much shorter follow up timeframes, and their results are not comparable to that of our study (12, 13). in the univariate analyses performed in yeo et al.’s study, age and hypertension, were significantly related to the readmission of covid-19 patients, but in their multivariate analysis model, these two variables became non-significant in relation to readmission (14). in their study, stepwise models were not utilized to identify independent prognostic factors for readmission. as a result, if they would have used stepwise models, which is a more precise multivariate analysis method for identifying prognostic factors, different results would/could have been obtained. in line with the findings of the present study, woo-hwi et al. also concluded that older age is a risk factor for the readmission of covid-19 patients (9). the increase in mean arterial pressure during the first admission was concluded to be one of the factors contributing to readmission. likewise, ramirez et al. concluded that hypertension is associated with a greater probability of readmission (10). moreover, a significant relationship was observed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 6 between hypertension and readmission in atalla et al.’s study (19). hypertension or higher blood pressure, is a risk factor for the severe form of covid-19. hence, the status of the hypertensive patients is more critical than that of other patients, and their prompt discharge may result in increased chances of their readmission. 5. limitations one of the limitations of the present study was the loss of the 120 patients during our follow up period. nonetheless, this 16.3% loss is still lower than the 20% cut-off mentioned in the guidelines of the quality control of observational studies (20). subsequently, the effects of this loss are rather inconsiderable. furthermore, the cause of readmission in 15.1% of the patients was cardiovascular accidents. although cardiovascular complications are one of the prevalent complications of covid-19, but the mentioned cardiovascular accidents may not be completely attributable to covid-19. eventually, the retrospective design of the present study, limited the researchers’ ability to investigate all of the probable risk factors and prognostic factors affecting readmission. 6. conclusion readmission is a relatively common phenomenon in covid19 patients. the six-month follow up preformed revealed an overall readmission rate of 8.6% in covid-19 patients, the risk of which may increase with older age and with an elevated mean arterial pressure. it seems that the lack of resources may be the underlying factor for the early discharge of covid-19 patients in the peak of the pandemic, leading to the increase in readmission probability. therefore, it is recommended that older or hypertensive patients’ discharge be performed cautiously to reduce their readmission. 7. declarations 7.1. acknowledgments the authors kindly appreciate all staff members of imam hossein hospital who helped us to collect the data and perform this study. 7.2. data availability the data is at the disposal of the corresponding author of the article and it it can be made available to the researchers upon request. 7.3. authors’ contributions study design: mha, my collecting and cleaning the data: all authors analysis and interpretation of results: ap, at, amn drafting: my, at, amn revising: all authors 7.4. funding and supports this study was supported by shahid beheshti university of medical sciences. 7.5. conflict of interest there is no conflict of interest. references 1. world health organization. who director-general’s remarks at the media briefing on 2019-ncov on 11 february 2020 genova: world health organization; 2020 [available from: https://www.who.int/directorgeneral/speeches/detail/who-director-general-sremarks-at-the-media-briefing-on-2019-ncov-on-11february-2020. 2. world health o. weekly epidemiological update 2020 [available from: https://www.who.int/docs/defaultsource/coronaviruse/situation-reports/20201005weekly-epi-update-8.pdf. 3. guan w-j, ni z-y, hu y, liang w-h, ou c-q, he j-x, et al. clinical characteristics of coronavirus disease 2019 in china. n engl j med. 2020;382(18):1708-20. 4. madanineishaboori a, moshrefiaraghi d, ali km, toloui a, yousefifard m, hosseini m. central nervous system complications in covid-19 patients; a systematic review and meta-analysis based on current evidence. arch acad emerg med. 2020;8(1):e62. 5. guan w-j, liang w-h, zhao y, liang h-r, chen z-s, li y-m, et al. comorbidity and its impact on 1590 patients with covid-19 in china: a nationwide analysis. eur respir j. 2020;55(5):2000547. 6. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. lancet. 2020;395:1054-62. 7. emami a, javanmardi f, pirbonyeh n, akbari a. prevalence of underlying diseases in hospitalized patients with covid-19: a systematic review and meta-analysis. arch acad emerg med. 2020;8(1):e35. 8. khateri s, mohammadi h, khateri r, moradi y. the prevalence of underlying diseases and comorbidities in covid-19 patients; an updated systematic review and meta-analysis. arch acad emerg med. 2020;8(1):e72. 9. jeon w-h, seon jy, park s-y, oh i-h. analysis of risk factors on readmission cases of covid-19 in the republic of korea: using nationwide health claims data. int j environ res public health. 2020;17(16):5844. 10. parra lm, cantero m, morras i, vallejo a, diego i, jimenez-tejero e, et al. hospital readmissions of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e48 discharged patients with covid-19. int j gen med. 2020;13:1359–66. 11. donnelly jp, wang xq, iwashyna tj, prescott hc. readmission and death after initial hospital discharge among patients with covid-19 in a large multihospital system. jama. 2021;325(3):304-6. 12. richardson s, hirsch js, narasimhan m, crawford jm, mcginn t, davidson kw, et al. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area. jama. 2020;323(20):2052-9. 13. somani ss, richter f, fuster v, de freitas jk, naik n, sigel k, et al. characterization of patients who return to hospital following discharge from hospitalization for covid19. j gen intern med. 2020;35(10):2838-44. 14. yeo i, baek s, kim j, elshakh h, voronina a, lou ms, et al. assessment of thirty-day readmission rate, timing, causes, and predictors after hospitalization with covid19. j intern med.290(1):157-65. 15. ramzi zs. hospital readmissions and post-discharge allcause mortality in covid-19 recovered patients; a systematic review and meta-analysis. am j emerg med. 2022;51:267-79. 16. seyedalinaghi s, afsahi am, mohssenipour m, behnezhad f, salehi ma, barzegary a, et al. late complications of covid-19; a systematic review of current evidence. arch acad emerg med. 2021;9(1):e14. 17. zali a, gholamzadeh s, mohammadi g, looha ma, akrami f, zarean e, et al. baseline characteristics and associated factors of mortality in covid-19 patients; an analysis of 16000 cases in tehran, iran. arch acad emerg med. 2020;8(1):e70. 18. gholamzadeh s, mohammadi g, looha ma, akrami f, zarean e, vafaee r, et al. baseline characteristics and associated factors of mortality in covid-19 patients; an analysis of 16000 cases in tehran, iran. arch acad emerg med. 2020;8(1):e70-e. 19. atalla e, kalligeros m, giampaolo g, mylona ek, shehadeh f, mylonakis e. readmissions among patients with covid-19. int j clin pract. 2020;75(3):e13700. 20. health nio. study quality assessment tools| national heart, lung, and blood institute (nhlbi) united states: national institutes of health; 2014 [available from: https://www.nhlbi.nih.gov/health-topics/studyquality-assessment-tools. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 8 figure 2: readmission rate among covid-19 patients based on the time of readmission (a) and cause of readmission (b). covid-19 relapse: relapse of covid-19-related symptoms or its respiratory complication. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e55 or i g i n a l re s e a rc h digital (two-finger) versus video laryngoscopy for nasogastric tube insertion in intubated patients; a clinical trial study mehdi nasr isfahani1, elahe nasri nasrabadi1∗ 1. emergency medicine department, alzahra hospital, isfahan university of medical sciences, isfahan, iran. received: june 2021; accepted: july 2021; published online: 16 august 2021 abstract: introduction: performing nasogastric tube (ngt) insertion is very challenging in anesthetized and intubated patients. the current study aimed at comparing digital (two-finger) and video laryngoscopy methods for ngt insertion in the mentioned patients. methods: the present single-blind clinical trial was performed on 76 intubated patients, who were randomly divided into two groups. groups a and b underwent video laryngoscopy and digital (two-finger) methods, respectively. then, the success rate, the number of attempts to insert ngt, duration of insertion, hemodynamic parameters, and patients’ satisfaction level were recorded and compared between groups. results: the mean duration of ngt insertion in group a was significantly higher than that of group b (19.07 ± 2.07 vs 11.53 ± 2.16 seconds; p value=0.001). the success rate was higher in group b (94.7% vs. 78.9%; p value=0.042). considering the interfering factors such as patients’ body mass index (bmi), the odds of success in group b was reported to be 8.49 times higher than that of group a (p value =0.028). conclusion: digital method can be considered as a safe and appropriate method of ngt insertion for intubated cases with high success rate and speed of performance. keywords: laryngoscopy; enteral nutrition; laryngoscopy; intubation, gastrointestinal cite this article as: nasr isfahani m, nasri nasrabadi e. digital (two-finger) versus video laryngoscopy for nasogastric tube insertion in intubated patients; a clinical trial study. arch acad emerg med. 2021; 9(1): e55. doi: https://doi.org/10.22037/aaem.v9i1.1281. 1. introduction one of the most frequent procedures in emergency departments (ed) is nasogastric tube (ngt) insertion. it is applied in mechanically ventilated patients for different purposes, such as decompression of stomach, reducing the pressure on the lungs for better breathing and respiration, preventing the risks of emptying the gastric contents during aspiration, and feeding (1-4). although this procedure is frequently done, it is very challenging to insert ngt in anesthetized patients due to patients’ lack of cooperation and inability to swallow. in addition, in many cases, attempts to insert the ngt result in failure to properly insert the tube into the stomach (5). there is a variety of ngt insertion methods for intubated patients in eds, among which digital and video laryngoscopy are two routine methods that can be employed (6). the dig∗corresponding author: elahe nasri nasrabadi; department of emergency medicine, isfahan university of medical sciences, isfahan, iran. email: elahe.nasri@resident.mui.ac.ir,tell: +98 913 113 5042, orcid id: https://orcid.org/0000-0001-6507-8456. ital method is a practical method that is performed in most eds, in which ngt insertion is performed with the help of the fingers by depressing the tongue and creating a suitable space (7). in video laryngoscopy, which is an alternative to conventional methods that are usually performed blindly, a color monitor that directly shows the glottis is used (8). the present study was performed to evaluate the success rates of digital (two-finger) and video laryngoscopy methods in insertion of ng tube in intubated patients in the eds. 2. methods 2.1. study design and setting the present study was a single-blind randomized clinical trial (number of rct: nct04414839), which was conducted on intubated patients in the eds of al-zahra and ayatollah kashani hospitals in isfahan, iran during 2018-2019. the study protocol was approved by ethics committee of isfahan university of medical sciences (under the number: ir.mui.med.rec.1397.287) and a written informed consent was obtained from the participants before inclusion in the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr isfahani and e. nasri nasrabadi 2 study. 2.2. participants 18 65-year-old patients in the mentioned eds, who underwent rapid sequence intubation (rsi) and required ngt insertion were included. cases with skull base fracture symptoms, coagulopathy and hemorrhagic disorders, maxillofacial traumas leading to the deformity and disturbance in ngt insertion, diseases and anomalies of the upper respiratory tract, deviated nasal septum, nostril stenosis, esophageal disorders (esophageal stricture, esophageal varices), and a history of head and neck radiotherapy, as well as patients intubated in and transferred from other centers were excluded. in addition, patients with more than two unsuccessful attempts at ngt insertion were excluded from the study. 2.3. data gathering patients were randomly divided into two groups using random allocation software and simple randomization method. each group was subjected to ngt insertion using either the digital or the video laryngoscopy method. first, demographic data including patients’ age, sex, weight, and height were recorded. then, all patients underwent continuous blood pressure (bp) monitoring. then, their pulse rate (pr), systolic blood pressure (sbp), diastolic blood pressure (dbp), and oxygen saturation percentage (o2sat) were recorded at baseline. in addition, the possible adverse events including mucosal bleeding, hemodynamic abnormalities (hypertension, tachycardia, and arrhythmia), esophageal perforation, and kinking and twisting of the ngt were recorded for all patients. pr, sbp, dbp, and o2sat were also evaluated and recorded at the end of the procedure. moreover, inserter’s satisfaction level was scored and recorded on a scale ranging from 1 (low satisfaction) to 10 (very high satisfaction). 2.4. procedure after making sure that the patient’s condition was favorable, and the intubation and resuscitation devices were ready, the patients were oxygenated with ambu bag and mask for three minutes. then, for induction of analgesia and anesthesia, all patients received the same medicines as follows: fentanyl 3 µg/kg, etomidate 0.3 mg/kg, and succinylcholine 1.5 mg/kg). then, they underwent intubation using rsi technique with tubes of similar size (men: 7.5-8mm internal diameter and women: 7-7.5 mm internal diameter). moreover, for all patients, endotracheal tube (ett) cuff was also inflated with air to maintain the ett cuff pressure within the range of 15-25 cm of water and the cuff was then fixed in its proper place. whether ngt insertion was successful or not, we didn’t open the cuff for better insertion and cuff pressure was maintained. before ngt insertion, the appropriate length of ngt for proper insertion into the patient’s stomach was first measured by placing the ngt tip on the patient’s xiphoid and extending it to the tip of the nose and then to the patient’s earlobe. it must be mentioned that since the patients could not cooperate to perform deep exhalation through the nose, the larger nostril was selected for ngt insertion based on the size of nostrils. all patients received 3 ml of lubricant gel and lidocaine anesthetic along with phenylephrine nasal drops in their selected nostril 5 minutes before ngt insertion. moreover, ngt no. 14-16 was used for all patients in accordance with the selected method. in the ngt video laryngoscopy group (group a), first, the glidescope blade was inserted under direct vision via the color monitor through the patient’s mouth by employing jaw-thrust maneuver to preserve the cervical spine and by raising the tongue to obtain a better view of the larynx space. then, ngt was inserted through the selected nostril, advanced through the esophagus under direct vision to meet the measured length, and was fixed after confirmation. in the ngt digital intubation group (group b), the second and third fingers were placed in the posterior pharynx and the tongue was depressed downwards. the ngt was passed through the nose into the posterior pharynx with the fingers in the pharynx to reach the esophagus. the thumb was placed under the jaw and pushed it forward to pave the way for tube insertion (fig. 1). it should be noted that in both groups ngt was inserted by a senior emergency resident, who had proven competency in ngt insertion for anesthetized intubated patients using both techniques. in addition, to check the proper placement of the ngt, an irrigation syringe instilled a 30cc air bolus into the patient’s stomach and stethoscope was used to simultaneously listen over the epigastrium. if the entrance of air into the stomach produced a whooshing sound, the proper placement of ngt was confirmed. if the first attempt at ngt insertion was successful, it was considered as a successful attempt. however, if the first attempt failed, the ngt was completely removed and after cleaning was inserted again using the same method. if both ngt insertion attempts were unsuccessful, the ngt was inserted using another method (fig. 2). in all groups, the duration of ngt insertion was measured by another individual using a stopwatch. the start time was when ngt entered the selected nostril, and the end time was when the measured ngt length had fully entered the stomach. it must be mentioned that blinding of the researcher was not possible due to the different natures of the two methods of ngt insertion; however, the data recorder and analyst were not informed of the difference of the two methods. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e55 figure 1: digital (two-finger) method in supporting nasogastric tube (ngt) insertion for intubated patients (from samuels le. nasogastric and feeding tube placement. in: roberts jr, hedges jr, editors. clinical procedures in emergency medicine. 4th ed. philadelphia: saunders; 2004. pp. 794-816). therefore, the present study was a single-blind study. 2.5. statistical analysis considering a confidence interval of 95%, a test power of 80%, and based on the findings of previous studies, reporting the success rates of 54% and 92% for successful ngt insertion in the conventional and digital methods, respectively, the sample size of 38 patients was considered for each group. the mentioned sample was selected using convenience random sampling. finally, the collected data were entered into spss software (ver.23). the data were presented as mean±standard deviation or frequency (percentage). in addition, based on the results of kolmogorov-smirnov test indicating the normality of data distribution, an independent samples t-test and fisher’s exact test were used to compare the means of quantitative variables and to compare the frequency distribution of discrete data, respectively. moreover, logistic regression with the enter method was used to evaluate the factors affecting the odds of success in ngt insertion. in all analyses, significance level was considered to be p values less than 0.05. 3. results group a included 22 (57.9%) males and 16 (42.1%) females with the mean age of 51.05 ± 10.14 years. group b consisted of 17 (44.7%) males and 21 (55.3%) females (p = 0.359) with the mean age of 53.39±10.53 years (p = 0.327). there was no significant difference between the two groups in terms of height (p=0.106), weight (p=0.330), and bmi (p=0.836). in addition, the success rate of 94.7% recorded for group b was significantly higher than the success rate of 78.9% obtained for group a (p=0.042). in addition, in more than 80% of patients in group b the first insertion attempt was successful (p= 0.043). the mean duration of insertion in group b with 11.53 ± 2.16 seconds was significantly lower than that of group a with 19.07 ± 2.07 seconds (p= 0.001) (table 1). furthermore, evaluation of the mean of each of the hemodynamic parameters including pr, sbp, dbp, and o2sat indicated that there was no significant difference between the two groups before and after ngt insertion (p-value> 0.05) (table 2). furthermore, inserter’s satisfaction level in group a with the mean score of 6.66±2.82 was significantly lower than that of group b with the mean score of 8.82 ± 1.99 (p=0.001). in addition, the only adverse event of this procedure was kinking and twisting of the ngt in groups a and b with 18.4% and 7.9%, respectively, the rate of which was not significantly different between the two groups (p=0.175). the results of evaluating the factors affecting the success of ngt insertion indicated that the success rate was significantly higher in group b compared with group a (odds: 8.49; 95% ci: 1.26-27.12; p = 0.028). in addition, with increase in bmi, the odds of success in ngt insertion decreased 0.80 times (p= 0.013); however, age (p =0.725) and sex (p = 0.763) had no significant effect on the success rate of ngt insertion (table 3). 4. discussion based the results of the present study, the digital intubation method was more successful than the video laryngoscopy method (success rate: 94.7 vs. 78.9%). in addition, the frequency of the first successful insertion attempt was significantly higher in group b compared with group a. one possible reason for the difference in the success rates in the first attempt may be that using fingers helps open the throat. many other factors such as choosing the right size, flexibility, and temperature of ngt should be taken into account in the process of insertion. for instance, choosing a larger size would result in less flexibility. ngt insertion in ice leads to a higher rate of success in the first insertion attempt (6, 9, 10). the number of failed attempts using the digital method is much lower than that of the conventional method. in addition, the speed of providing services when using the digital method is significantly higher than that of the blind methods. the extent of the patient’s mouth opening, the presence or absence of teeth, the length of the neck, the lack of mechanical complications in the throat and respiratory tract, the experience and skill of the inserter, and the length of the physician’s fingers can be regarded as various factors that affect the quality of performing and success rate of the digital method this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr isfahani and e. nasri nasrabadi 4 figure 2: study flow chart. (7). on the other hand, video laryngoscopy reduces not only the failure rate for the first attempt but also the side effects on the soft tissue of the throat compared with the conventional method. this method prevents the formation of pneumonia caused by the entry of gastric contents into the lungs and increases the accuracy of directing ngt to larynx (8). despite all the above-mentioned positive points about this method, the disadvantages of this method are also significant. some drawbacks of this method include the use of stylet to adjust the insertion tube, the hardship of entering the tube through the glottis, and the limitations of utilizing the device due to the limited mouth opening. in addition, some devices employed in this method are sometimes heavy, while lighter and more portable devices have a smaller screen (8). furthermore, the present study revealed that the duration of ngt insertion in group b was significantly lower than that of group a, and the emergency physician performed the ngt insertion process at very high speed in group b, which naturally led to inserter’s higher satisfaction (11.5 vs. 19.7 seconds). finding the epiglottis employing the video laryngoscopy method increased the time of insertion, while using fingers and depressing the tongue with two fingers in the digital method led to better direction of the tube to the esophagus, which minimizes the possibility of tube twisting and physical damage. tantri’ et al.’s study revealed that the success rate of ngt insertion at the first attempt in the finger method was significantly higher than that of the reverse sellick maneuver method. in addition, the incidence of complications in the finger method has been very low. therefore, they stated that the finger method is a feasible and safe method for ngt insertion (11). although the finger method used in their study was different from the finger method employed in the current study, it can be stated that despite not using special and adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e55 table 1: comparing the baseline characteristics of patients between video laryngoscopy (group a) and digital intubation (group b) groups variables group a (n=38) group b (n=38) p-value gender; male 22(57.9) 17(44.7) 0.359 age; year 51.05±10.14 53.39±10.53 0.327 height; cm 170.43±9.71 164.92±9.71 0.106 weight; kg 71.51±13.29 67.95±17.82 0.330 body mass index 24.56±3.96 24.79±5.75 0.836 success rate 30(78.9) 36(94.7) 0.042 1s t attempt insertion 23(60.5) 31(81.6) 0.043 2s t attempt insertion 7(18.4) 5(13.2) 0.744 duration of ngt insertion; seconds 19.07±2.07 11.53±2.16 <0.001 data are presented as mean ± standard deviation or frequency (%). ngt: nasogastric tube. table 2: comparing the hemodynamic parameters before and after nasogastric tube insertion between video laryngoscopy (group a) and digital intubation (group b) groups variables group a group b p-value pr before 76.51±6.36 77.91±5.95 0.326 after 78.09±6.25 78.53±6.96 0.772 sbp before 103.37±8.28 103.39±8.46 0.989 after 110.03±7.20 108.00±7.36 0.229 dbp before 66.95±6.41 67.75±7.70 0.624 after 67.92±7.96 68.83±7.96 0.620 o2sat before 97.30±1.61 97.16±1.24 0.670 after 97.91±0.64 97.92±0.67 0.920 data are presented as mean ± standard deviation. pr: pals rate, sbp: systolic blood pressure, dbp: diastolic blood pressure, o2sat: oxygen saturation. vanced devices and lack of changes in the position of the patient’s head and neck, this method could yield higher success rate by taking advantage of the knowledge of the patient’s anatomical condition. the hemodynamic parameters of patients before and after ngt insertion revealed that patients had stable clinical symptoms, and pr, sbp, dbp, and o2sat did not significantly change in any of the patients. however, in their article about cardiovascular responses to the ngt insertion, fassoulaki et al. found that sbp significantly increased immediately after ngt insertion using both blind finger and laryngoscope methods. however, 3 minutes after the insertion, sbp was still significantly higher only in laryngoscope method. pr had also increased in both methods. o2sat also increased dramatically after ngt insertion. in the end, they concluded that insertion of ngt in anaesthetized patients should ideally be done using the blind finger method (12). the mentioned lack of changes in both methods, despite the presence of advanced devices in the video laryngoscopy method, indicates the safety of the digital method and the ease of using this method. however, the consensus of emergency physicians recommends the use of video laryngoscopy method for patients with pharyngeal complications, obese patients, patients with esophageal and upper respiratory tract cancers, or patients with cervical spinal cord injuries. in addition, the level of inserter’s satisfaction in method b (digital) was reported to be higher than that of method a (video laryngoscopy). the mentioned finding can be of great value as consideration of the inserter’s satisfaction and their lower annoyance are of particular significance for physicians in clinical interventions. this satisfaction may be attributed to the shorter duration of tube insertion in the digital method compared with the video laryngoscopy method or may be ascribed to the high success rate of tube insertion in the first attempt in group b. given the lack of differences in tube insertion problems such as ngt kinking and twisting between the two methods, it can be concluded that the digital method can be used safely and quickly for tube insertion in the eds. nevertheless, tantri et al. found that finger method had a lower blood spot complication and kinking or coiling of ngt, which is possibly due to better guidance of the tube using fingers by fixing the tip of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr isfahani and e. nasri nasrabadi 6 table 3: determining the factors affecting the success of nasogastric tube insertion factors beta s.e. or (95% ci) p-value digital vs video laryngoscopy 2.14 0.97 8.49 (1.26-27.12) 0.028* age 0.01 0.04 1.01 (0.94-1.09 ) 0.725 sex 0.24 0.78 1.27 (0.27-5.85) 0.763 bmi -0.22 0.09 0.80 (0.67-0.95) 0.013* *: p-value less than 0.05 indicates a significant effect on the success rate. bmi: body mass index; or: odds ratio; ci: confidence interval. ngt right at the entrance of the esophagus (11). the results of logistic regression analysis in identifying the factors influencing the successful insertion of ngt revealed that although age and sex did not affect the success rate, the patients’ bmi had a significant effect on the success rate of ngt insertion. the higher the bmi of the patients, the less likely they are to have successful ngt insertion. in addition to this interfering effect, method b increases the success rate many times compared with method a. in a review article by liao et al., the issue of obesity and its negative effects on tube insertion has been discussed. they noted that tube insertion in obese patients is a major challenge for the emergency physicians, for whom guiding ngt in the right position is difficult due to abnormal anatomy of the glottis, e.g. narrowing of the upper airways, which leads to a significant decrease in spo2 or functional residual capacity during intubation (13). since the time-consuming and difficult nature of ngt insertion in obese patients leads to hypoxia, many physicians recommend the use of video laryngoscopy method in these patients (13). however, few reports stated that bmi was not a factor influencing the success rate of this process (14). prominent studies have only focused on airway tracheal tube methods and have not directly mentioned ngt insertion. we suggest that larger studies can address the impact of bmi on the success rate of ngt insertion and its related complications. therefore, the main advantage of the present study can be selection of the appropriate method considering the interfering factors such as patients’ bmi, which can cause the least damage to the cervical spinal cord and also have the lowest risk for the patient. in fact, this study revealed that although both methods are common and documented, the use of digital method can be preferred over the video laryngoscopy method due to not applying sophisticated devices, uncomplicated process of learning and training, and its ease of use. on the other hand, the video laryngoscopy method can cause fewer physical complications for the patient as it provides better vision for novice residents. the mentioned advantages can be obtained depending on the presence or absence of advanced devices. although the video laryngoscopy method can be used in large and well-equipped hospitals, the digital method can be used easily and without high costs in small hospitals or clinics, where ngt insertion must be performed as soon as possible. since our study demonstrated the lower success rate of the video laryngoscopy method, use of mcgill forceps is recommended for better guiding of tube into the glottis in this method. also, due to moral issues regarding icu patients, for whom we are not allowed to insert ngt in the nostrils, it is suggested to insert the ngt directly through the mouth. in addition, from our experience, use of frozen ngt leads to better insertion outcomes. furthermore, higher bmi level was one of the factors affecting the success rate of ngt insertion. thus, recruiting those with high bmis in a larger study to evaluate the exact role of bmi on the success rate of ngt insertion in both video laryngoscope and digital methods is recommended. digital method can be used in medical centers due to its ease of implementation, practicality, availability, and lack of need for advanced and expensive devices. however, application of new methods and integrating them with conventional ones can yield a more desirable outcome and a very high success rate. it is suggested to conduct future studies with a larger sample size and a similar design in order to achieve more definitive results generalizable to the population. 5. limitation the small sample size and the impossibility of doubleblinding due to the type of devices and the technique of the ngt insertion can be regarded as limitations of the present study. moreover, the implementation of this study in educational centers by trained assistants can be considered as another limitation. however, it is also worth noting that trained assistants implementing the digital technique have been able to achieve a high success rate in ngt insertion using fewest readily available devices. the mentioned point can be an indication of the safety of this method. 6. conclusion based on the results of the present study, the success rate of ngt insertion and the number of successful first attempts have been significantly higher in the digital method comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e55 pared with video laryngoscopy method. in addition, the speed of performing this process was significantly higher in the digital method compared with the video laryngoscopy method. however, it must be mentioned that the stability of patients’ hemodynamic parameters and the occurrence of adverse events were not significantly different between the two methods. 7. declarations 7.1. acknowledgments we would like to express our gratitude to the staff of emergency medicine departments of al-zahra and ayatollah kashani hospitals affiliated to isfahan university of medical sciences. 7.2. conflict of interest the authors declare they have no conflict of interest. 7.3. funding this work was supported by deputy of research and technology of isfahan university of medical sciences (grant# 397585). 7.4. authors’ contribution e. nn: conceptualization; data collection; investigation; writing the original draft. m. ni.: conceptualization; methodology; project administration; supervision; review and editing. references 1. isfahani mn, heydari f, azizollahi a, noorshargh p. comparison of three methods for ng tube placement in intubated patients in the emergency department. advanced journal of emergency medicine. 2020; 5(1): e6. 2. mandal mc, dolai s, ghosh s, mistri pk, roy r, basu sr, et al. comparison of four techniques of nasogastric tube insertion in anaesthetised, intubated patients: a randomized controlled trial. 2014;58(6):714. 3. mandal m, karmakar a, basu srjijoa. nasogastric tube insertion in anaesthetised, intubated adult patients: a comparison between three techniques. 2018;62(8):609. 4. roberts jr. roberts and hedges’ clinical procedures in emergency medicine and acute care e-book: elsevier health sciences; 2017. 5. ghatak t, samanta s, baronia akjnajoms. a new technique to insert nasogastric tube in an unconscious intubated patient. 2013;5(1):68. 6. appukutty j, shroff ppja, analgesia. nasogastric tube insertion using different techniques in anesthetized patients: a prospective, randomized study. 2009;109(3):8325. 7. alcalde hm, martínez jb, rubio amjtia, care c. digital intubation: never blind anymore. 2016;6:28-31. 8. jaber s, de jong a, pelosi p, cabrini l, reignier j, lascarrou jbjcc. videolaryngoscopy in critically ill patients. 2019;23(1):221. 9. chun d-h, kim ny, shin y-s, kim shjwjos. a randomized, clinical trial of frozen versus standard nasogastric tube placement. 2009;33(9):1789-92. 10. fakhari s, bilehjani i, negargar s, mirinezhad m, azarfarin r. split endotracheal tube as a guide tube for gastric tube insertion in anesthetized patients: a randomized clinical trial. 2009. 11. tantri ar, mangkuwerdojo ljmjoi. a randomized clinical trial of nasogastric tube insertion in intubated patient: comparison between finger method and reverse sellick maneuver. 2019;28(4):311-5. 12. fassoulaki a, athanassiou e. cardiovascular responses to the insertion of nasogastric tubes during general anaesthesia. canadian anaesthetists’ society journal. 1985;32(6):651. 13. liao c-c, liu f-c, li ah, yu h-pjeromd. video laryngoscopy-assisted tracheal intubation in airway management. 2018;15(4):265-75. 14. cavus e, thee c, moeller t, kieckhaefer j, doerges v, wagner kjba. a randomised, controlled crossover comparison of the c-mac videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia. 2011;11(1):6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e1 or i g i n a l re s e a rc h proposing an emergency medicine ethical guideline; a qualitative study leili asadabadi1, kamran soltani nejad2, atefeh zolfagharnasab3, mina mobasher4∗ 1. clinical research unit, shahid bahonar academic center, kerman university of medical sciences, kerman, iran. 2. afzalipour faculty of medicine, kerman university of medical sciences, kerman, iran. 3. department of library and medical information, faculty of management and medical information sciences, kerman university of medical sciences, kerman, iran. 4. department of medical ethics and history of medicine, faculty of iranian traditional medicine, kerman university of medical sciences, kerman, iran. received: november 2021; accepted: november 2021; published online: 1 january 2022 abstract: introduction: emergency medicine physicians face major ethical challenges in their practices. furthermore, they need to be aware of the principles of ethical analysis and clinical decision-making in order to provide quality care. this study aimed to propose professional ethics codes in the emergency medicine department. methods: this is a qualitative study, which was performed using narrative review and expert panel, and was conducted in three steps, including: literature review and preparation of the initial draft of the ethical concepts, obtaining expert opinions on this initial draft and its validation, and finalizing main ethical components in emergency medicine. in this study, we received the opinions of an expert panel including 10 medical ethicists and 12 emergency medicine specialists using a survey form. results: the ethical guide to emergency medicine can be formulated in 34 key ethical concepts, 6 sub-components, and 5 main components including emergency physician-patient relationship, and emergency physicians’ relationships with other professionals, students, researchers, and community. conclusion: emergency care providers need to be familiar with ethical guidelines in order to improve quality of care in emergency departments. the findings of this study suggest that a guideline on patient-physician relationship as well as the emergency physicians’ ethical obligations for other professionals, students, researchers, and community should be developed in line with ethical norms. keywords: codes of ethics; emergency medicine; practice guideline; physician-patient relations cite this article as: asadabadi l, soltani nejad k, zolfagharnasab a, mobasher m. proposing an emergency medicine ethical guideline; a qualitative study. arch acad emerg med. 2022; 10(1): e1. https://doi.org/10.22037/aaem.v10i1.1391. 1. introduction emergency medicine physicians face major ethical challenges in their practices due to criticality of situations in the emergency department as well as the advances of knowledge and technology in health care services. consequently, they need individual knowledge and group discussions to make decisions. there is a consensus that moral sensitivity is one of the requirements of physicians’ practice in emergency medicine settings (1). the ethical responsibilities of emergency physicians in patient care require that they be ∗corresponding author: mina mobasher; afzalipour faculty of medicine, kerman university of medical sciences, 22nd bahman blvd., kerman, iran. tel: 0098-34-33257660-4. fax: 0098-34-33257671. email: m.mobasher@kmu.ac.ir, orcid: http://orcid.org/0000-0002-7115-861x. aware of their professional values, and the principles of ethical analysis. furthermore, ethical codes are a systematic guide for shaping the ethical behaviors of people (2). emergency physicians should be aware that there may be controversial ethical challenges in each of the medical procedures (3). the principles, rules, and ethical standards have been developed at the organizational, national, and even global levels and introduced as professional ethical guidelines for many professions, and professionals are obliged to abide by it (4). according to the american emergency medicine association (aema) recommendations, emergency medicine practitioners must be actively engaged in professional ethics in order to ensure the provision of optimal care in the process of clinical decision-making. the performance quality of emergency medicine physicians this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. asadabadi et al. 2 can improve and contribute to the integration of moralitybased practices in different situations provided that there are professional ethics standards and they are practiced (5). moreover, if medical students and residents work according to ethical principles taught to them during their training in emergency medicine, these principles improve their professional behaviors and moral decision-making, and this is critically important in their professional practice in the future. emergency physicians should engage in educational programs related to ethical reasoning in order to be able to resolve ethical challenges in complicated situations of emergency departments (6). teaching the emergency staff about ethical dilemmas in emergency medicine and developing or providing access to appropriate resources such as ethical guidelines can be very helpful in managing difficult emergency situations and some aggressive patients and their families, as well as complex emergency situations (7). furthermore, a moral guide can also be a reliable tool to evaluate the performance of physicians as well as leading to unity of practice and strengthening the sense of responsibility and professional commitment in physicians. this study aimed to review resources, narratively, and clarify key ethical concepts and main components of the ethical issues in the emergency medicine department. 2. methods 2.1. study design and setting the present study is a qualitative study that was conducted in three main steps. the first step consisted of drafting the early version of the codes of emergency medicine that included three parts: 1) review of texts using content analysis and extraction of ethical concepts, 2) translating ethical concepts into codes and 3) completion of the code list by adding ethical codes of the other countries. 2.2. data gathering in order to extract ethical concepts, a search in the three international databases web of science, pubmed and scopus was conducted using the keywords ethics, code of ethics, emergency and ems in the title and abstract fields without any time limit until the end of 2020. also, a search was conducted in the persian language databases including magiran and sid with the keywords including emergency medicine, ethics, medical etiquette, education. in addition, the phrase code of ethics for emergency was used in the google search engine and the websites of the ministries of health in different countries in order to access relevant documents to provide codes of ethics related to emergency medicine in these countries. these documents are important sources of information that can make important contributions to a review, may reduce publication bias, and increase reviews’ comprehensiveness. figure 1 shows the process of extracting relevant articles (figure 1). two members of the research team checked on the credibility of the data source and its usability for our study using common sense and valid search engines. we studied the articles to identify the ethical concepts that are mentioned in a form of behavior (so as to indicate the engamenet in or abandonment of a specific behavior) related to the emergency department. the ethical concepts were merged and categorized. after achieving data saturation and the literature review was stopped. following this step, ethical concepts became a code of ethics. otherwise, it would have been written in form of do’s and dont’s that emergency medicine specialists should oblige. furthermore, to ensure the comprehensiveness of the obtained codes, the ethical codes related to the emergency medicine profession were collected from four countries based on availability and ease of access. finally, the first draft of the code of ethics was ready to enter the next step. in the second step of this qualitative study, we used expert sampling, a purposive sampling technique, to include only those with expertise in a certain area (emergency medicine and medical ethics). in fact, these experts are purposefully as different from each other as possible to help in identification and selection of information related to the ethical issues in emergency medicine practices. we try to reduce the biases in this study as much as possible by using this sampling. our experts were emergency medicine specialists and medical ethicists with different backgrounds from different universities of medical sciences in iran (kerman, qom, tehran, rafsanjan, mashhad). they announced that they did not have any conflict of interest. in this step of the study, we conducted a survey of experts by emailing them a survey form. the compiled text was sent to ten medical ethicists. according to five of their comments, the necessary modifications were carried out in the initial text by the medical ethicist in our research team. the second text was reread with members of the research group and the required modifications were made. the third version of the compiled text was sent to twelve emergency medicine experts through email and 6 of them sent their comments back. verbal and written explanation was given to these experts. also, in the survey step, in order to complete the validation of the obtained codes, experts on the subject were asked to express their views on the compiled text in terms of the clarity of the content of each code and its feasibility. the agreement of medical ethicists in the first stage and the agreement of emergency medicine specialties in the second stage produced data saturation. therefore, the depth and volume of data was suitable. in each step, the completed forms were reviewed, and based on the received suggestions, the necessary changes were made in the forms and writing styles of some codes. therethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e1 fore, some codes were combined, adjusted, or deleted, and the opinions of the above-mentioned expert groups were summarized. 2.3. statistical analysis finally, we could clarify the main components by placing similar ethical concepts into one subcomponent by applying the technique introduced in sandolowski study (8). in this way, the final set of proposed ethical codes in emergency medicine was formulated as the final edition and prepared to be presented to relevant authorities. in this study, we introduced key ethical concepts and main components of the ethical guidelines developed in emergency medicine. 2.4. ethical consideration this study was approved by kerman university of medical sciences in 2019 with the ethics code (ir.kmu.ah.rec.1398.015) obtained from the national ethics committee in biomedical research. 3. results we extracted 9750 documents to review their titles and abstracts and selected 221 documents for the final review. of the selected ones, 30 documents were used to compile the codes (figure 1), most of which were related to the united states (12 documents) and iran (5 documents), respectively. there were two documents related to the philippines. articles (one for each country) were from new zealand, the united kingdom, turkey, saudi arabia, pakistan, and canada. also, five documents were co-written (table 1). ethical codes of the countries showed that the general responsibilities of emergency physicians all over the world were considered the responsibility of emergency physicians toward patients’ rights in terms of obtaining informed consent, maintaining privacy and patients’ best interests as well as the social responsibility of emergency physicians and their responsibility toward their colleagues and the community. the ethical concepts are mentioned in a form of behavior (so as to indicate the engamenet in or abandonment of a specific behavior) related to the emergency department furthermore, results of the first and second step of our study showed 34 key ethical concepts in the scope of emergency medicine physicians’ practice (table 2). according to the results, guidelines that generally apply to ethical compliance in emergency medicine include the principles of respect for autonomy, beneficence, nonmaleficence, and justice in medicine. furthermore, the importance of strengthening ethical virtues in the performance and flexibility of emergency physicians should be emphasized in triage and in the complex challenges and situations of emergency medicine. therefore, paying attention to the prevailing values in emergency medicine such as adherence to the six professional behaviors including altruism, responsibility, honesty and integrity, respect for others, excellence, and justice was very important. in addition, work conscience, discipline, good mood, attention to the patient and her/his wishes, making trust, adherence to rules and regulations, and acceptance of responsibility for error were important values in emergency medicine. finally, the ethical concepts were categorized in five main components and 6 subcomponents in this area (table 2). 4. discussion in this study, the general structure of the necessary ethical concepts in iranian emergency medicine were proposed based on the opinions of experts on the subject and the concepts in the articles and the structure of codes in other fields of medical sciences in iran as well as other countries. according to the results of this study, the general structure of the proposed ethical guideline of emergency medicine included five main components, the relationship between the emergency physician and the patient, other professionals, students, research group, and the community. one of the important concepts of the present study for emergency physicians was considering the interests of emergency patients, which is in the results of other studies and codes from other countries (9-16) as well as the guide provided by the american emergency medicine association (5). the emergency physicians need to pay more professional attention to their patients’ interests in emergency departments. this principle can indicate paying attention to the patient’s pain, and physical and mental sufferings that should be reduced by physicians as much as possible. another suggestion of the present study for emergency physicians is to observe non-maleficence to patients, which was also reported in the results of similar studies (6, 13, 1518) and the other codes (5, 14). there are degrees of risk or side effects in many emergency cases due to the excessive overcrowding and complex conditions prevailing in the emergency department; therefore, emergency physicians are obliged to assess the condition and the possibility of harming patients and make a suitable decision. trying to enhance the knowledge and skills of emergency physicians was one of the ethical codes, which can also be identified in the other studies (9, 12, 19, 20). improving physicians’ knowledge and skills can be classified as one of the codes that significantly affect other concepts in this study, such as benefit for patients, non-maleficence, improving the quality care, and attention to students’ education. when the emergency specialist increases his/her scientific and practical knowledge, he/she can certainly provide better and more effective care for patients. hence, emergency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. asadabadi et al. 4 table 1: bibliographic profile of final included studies first author year country type language study design subjects data gathering new zealand medical association 2020 new zealand statement english qusai talat alwaznah 2019 saudi arabia review article english qualitative literature review keith a colaco 2018 canada article english quantitative staff nurses and physicians questionnaire helen askitopoulou 2018 book english diane gurney 2017 usa practice guideline english american college of emergency physicians 2017 usa statement english philippine medical association 2017 philippine statement english philippine medical association 2017 philippine statement english waleed zafar 2015 pakistan article english qualitative ed physicians in-depth interview maria f jime´nezherrera 2014 article english qualitative nurses interview; focus group müesser özcan 2014 turkey article english quantitative emergency care providers questionnaire anders bremer 2014 article english quantitative ambulance professionals torben k. becker 2013 usa guideline english john jesus 2012 book english catherine a. marco 2012 usa review article english qualitative review of affordable care act 2010 catherine a. marco 2012 usa review article english qualitative review of affordable care act 2010 gregory luke larkin 2009 review article english qualitative review khim horton 2007 uk review article english qualitative literature review rita sommers-flanagan 2007 usa review article english qualitative review bagher larijani 2007 iran review article english qualitative review kenneth v. iserson 2006 usa review article english qualitative review bagher larijani 2005 iran review article english qualitative review canadian medical association 2018 canada statement english john brown 1999 usa review article english qualitative review james adams 1998 usa review article english qualitative review bernard heilicser 1996 usa article english qualitative emergency medical technicians questionnaire kenneth v. iserson 1991 usa article english qualitative review acep ethics committee 1991 usa statement english akram izadikhah 2013 iran article english qualitative review; focus group mohsen shahriari 2011 iran thesis persian mix method nursing professionals review; interview; focus group amir ahmad shojaee 2011 iran article persian qualitative review sodabeh jolaee 2010 iran article persian qualitative nursing professionals review; focus group ed: emergency department. specialists should pay special attention to this issue. the results of similar studies (10, 11, 16, 19, 21, 22) and the ethical guideline provided by the american society of emergency medicine (5) emphasized the impartial performance this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e1 table 2: the relationships of participants’ characteristics with return of spontaneous circulation (rosc) main component sub-component key ethical concepts the relationship between the emergency physician and the patient patient’s rights • attention to the protection of the patient’s interests and privacy according to laws and regulations • benefits or risks of treatments • patient’s decision-making capacity and consent • patient’s transfer to other departments in accordance to laws and regulations • paying attention to the patients when they refuse treatment • attention to the rights of vulnerable patients and minorities • attention to the correct principles of resource allocation the relationship of emergency physicians with other professionals -rights of collegues -individual rights • paying attention to mutual communication and facilitating these relations in terms of protecting patients’ interests • not having prejudices • choosing counselors • correct transfer of patients’ care responsibilities • paying attention to patients’ disabilities • proper use of care protocols • coordination with personnel and maintaining dignity and personality • preventing deception and fraud and fighting against these problems • access to whose right to be supported in emergency challenges • non-acceptance of gifts relationships with students, interns, and other learners -patient’s rights student rights • the emergency physician is a role model for learners • closely monitoring the moral performance of learners • providing feedback to them • paying attention to the interests of patients in educational centers and obtaining their consent relations with research groups -patient’s rights research ethics • following the ethical guidelines in general and specific research • observing the main ethical requirements for research studies • taking responsibility for the protection of participants’ rights • gaining knowledge of the law and regulations on prevention of scientific fraud • active participation and supervision in research the relationship between the emergency physician and the community -patient’s rights community rights • being active in relation to legal, regulatory, organizational, and educational measures • non-discrimination and providing emergency services for all members of society • participating in continuous education activities and trainings necessary for the community • being aware of strategies for saving resources • proper cooperation with pre-hospital staff • making the right triage decisions • correct action against domestic violence and abuse • training to improve the health and safety of the community and fair behaviour of emergency physicians. furthermore, emergency physicians must deal with issues related to the distribution of scarce health care resources and decide which treatments the patients should receive and what facilities they should use in the emergency room due to the special conditions of the emergency department and the hospitalization of patients with unstable vital signs and lowered level of consciousness. so, it is necessary to practice with justice and fairness in the emergency department. respect for patient autonomy was another code of this study, which is a concept found in many studies (9-14, 16, 18-20, 23) and a guide provided by the american society of emergency medicine, and was also pointed out in the other studies from the united states, new zealand, and canada (5, 13, 15). of course, observing this code for emergency physicians is a little more difficult than physicians in other departments and requires more effort due to the emergency conditions of patients, the risk of patients’ mortality and morbidity, and time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. asadabadi et al. 6 figure 1: the flowchart of the extracted articles. constraints in this department. emergency specialists should try to provide patients with complete information and help their family members decide about the treatment as much as possible. improving the quality of patients’ care was selected as one of the ethical concepts in the codes of ethics in emergency medicine. this finding has been noted in other researches (9, 12, 19) and other ethical guidelines (5, 13, 15). in fact, improving the quality of patients’ care in this ward will reduce the patients’ mortality and morbidity more than other wards due to the nature of the emergency department. another ethical concept in this research was paying attention to students ’ training, which is a code of ethics present in the other ethical guidelines of emergency medicine (9, 19, 20). it is necessary that the clinical staff members of emergency departments, in addition to their comprehensive efforts to save patients’ lives, not neglect the educational issues related to all groups of students. because, the training process for interns and students of other related fields such as nursing and emergency medicine assistants is performed in the emergency department of public hospitals. eventually, these trainees will serve independently in some remote and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e1 sometimes deprived areas as the first line of treatment, so, if they receive the more practical and comprehensive training during their studies, they will definitely provide better services, which can certainly lead to reduced medical malpractice and patient mortality and morbidity. control of violence in emergency departments was another ethical concept of this research, which is also present in the results of similar researches (11, 12, 18, 20). this issue is important for emergency specialists due to the stressful and complex situations in the emergency departments and the low tolerance of the patients and their companions due to the occurrence of various accidents. the emergency medicine professionals should have more patience against verbal violence of patients and their companions and facilitate the treatment process through appropriate behavior with patients and other colleagues. resource allocation consideration and giving enough knowledge about this issue was another research concept that was present in the results of other researches (5, 11, 19, 24). considering the limited resources in the emergency department, especially in hospitals in developing countries, it is necessary for emergency specialists to have a good relationship with staff and university officials to meet their demands easily. also, when they are restricted or under adverse conditions, they should request for assistance in order to protect patients’ lives. protecting the life of every human being in any position and situation is the duty of the emergency medicine physician. the ethical responsibilities of emergency medicine physicians in their practice and care requires them to be aware of their beliefs, as well as the basis and principles of ethical analysis and decision-making. ethical rituals (or codes) are systematic guidelines to form moral behaviors. emergency medical professionals have the responsibility to decide and operate based on professional values in their career. since emergency medical practitioners are one of the most important groups of service providers who have a significant impact on the quality of healthcare provision, their compliance with professional ethics will also be an effective factor in improving the quality of care. in addition, a codified ethical guideline can provide a reliable tool for evaluating physicians’ performance for regulatory organizations. 5. limitations in the present study, the code of ethics published by the emergency medicine association of some countries such as the united states has been considered, which has been cited in many articles and studies of the other countries. but there was limited access to medical codes of emergency medicine in other countries. comparative research between public and private hospitals is also proposed to take place in the future so that the results can be used for making policies in this area. moreover, it is better to assess the views of a larger group of experts to finalize the general structure of the ethical codes of emergency medicine in iran. 6. conclusion moral sensitivity is one of the requirements of professional practice in emergency medicine settings. thus, a codified ethical guideline can establish an applicable policy for these specialists to increase their practical abilities and provide better, and more effective care for patients. in this regard, the findings of this study sheds light on a more rational solution to the ethical issues in emergency medicine physicians’ relationship with patients, other professionals, students, researchers, and communities. 7. declarations 7.1. acknowledgments this article is the result of a part of the dissertation by kamran soltaninejad in the emergency medicine specialty course in kerman university of medical sciences in 2020, approved by kerman university of medical sciences in 2019 with ethics code (ir.kmu.ah.rec.1398.015) obtained from the national ethics committee in biomedical research. the authors wish to express their deepest gratitude and warmest appreciation to all the medical ethicists and emergency medicine specialists who in any way have contributed and inspired the researchers. 7.2. author contribution study concept and design was performed by mina mobasher. searching the articles and other documents was performed by atefeh zolfagharnasab. considering the documents, extracting the articles were done by mina mobasher, leli sadabadi and kamran soltani nejad. content analysis, extracting the ethical concepts, and drafting of the ethical codes were done by mina mobasher, leli sadabadi, kamran soltani nejad and atefeh zolfagharnasab. all authors reviewed the final draft of this article. study supervision was performed by mina mobasher. 7.3. funding none. 7.4. conflict of interest the authors stated that there was no conflict of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. asadabadi et al. 8 references 1. askitopoulou h, singler k, frühwald t, weissenbergerleduc m. ethical issues of emergency medical care for older patients. in: nickel c, bellou a, conroy s, editors. geriatric emergency medicine. cham: springer international publishing; 2018. p. 369-95. 2. moskop 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[in persian]. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e44 or i g i n a l re s e a rc h door-to-antibiotic time and in-hospital mortality of elder patients presenting to emergency department with sepsis; a cross-sectional study siriwimon tantarattanapong1∗, thanaporn hemwej1 1. department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla 90110, thailand. received: april 2021; accepted: may 2021; published online: 11 june 2021 abstract: introduction: the current international sepsis guideline recommends that administration of intravenous broad-spectrum antibiotics should be initiated within 1 hour of emergency department (ed) arrival for sepsis patients. this study aimed to evaluate the association between door-to-antibiotic time and in-hospital mortality of these patients. methods: in this retrospective cross-sectional study, elderly patients (age ≥65 years) diagnosed with sepsis in the ed of a tertiary referral and academic hospital from january to december 2019 were enrolled. door-to-antibiotic time was defined as the time from ed arrival to antibiotic initiation. the associations of door-to-antibiotic time and each hour delay in first antibiotic initiation with in-hospital mortality were assessed. results: six hundred patients with the median age of 78.0 (iqr: 72.0-86.0) were studied (50.8% female). the median door-to-antibiotic time was 51.0 (36.0–89.0) minutes and in-hospital mortality rate was 12.5%. there was no significant difference in the in-hospital mortality rate between door-to-antibiotic time ≤1 hour and >1 hour (13.1% vs. 11.6%, p = 0.726). when considering hour-upon-hour of door-to-antibiotic time, no significant difference in in-hospital mortality was observed (p = 0.866). factors that led to a delay in doorto-antibiotic time were presenting body temperature <38°c (odds ratio [or] 3.34; 95% ci, 2.12-5.29; p < 0.001) and age <75 years (or 1.7; 95% ci, 1.09-2.64; p= 0.019). conclusion: door-to-antibiotic time was not associated with in-hospital mortality in elderly sepsis patients in this study. significant factors that led to a delay in door-to-antibiotic time were no fever, age <75 years, doctor time, and blood sample taking time. keywords: anti-bacterial agents; mortality; emergency service, hospital; quality of health care; sepsis; aged; aged, 80 and over cite this article as: tantarattanapong s, hemwej t. door-to-antibiotic time and in-hospital mortality of elder patients presenting to emergency department with sepsis; a cross-sectional study. arch acad emerg med. 2021; 9(1): e44. https://doi.org/10.22037/aaem.v9i1.1266. 1. introduction sepsis remains as a public health problem worldwide and is one of the leading causes of death (1). the incidence of sepsis was 437 cases per 100,000 person-years and has tended to increase as a result of an aging population and more comorbidities (2). sepsis is also the major cause of emergency department (ed) visits. the annual incidence of ed sepsis was 0.82% of total ed visits (3). elderly patients constitute 60% of all sepsis patients (4). likewise, elderly patients are ∗corresponding author: siriwimon tantarattanapong; department of emergency medicine, songklanagarind hospital, faculty of medicine, prince of songkla university, hat yai, songkhla, thailand, 90110. phone: (66)74451705, fax (66)74-451704, email: tsiriwimon.er@gmail.com, orcids: https://orcid.org/0000-0002-4792-373x. an increasing proportion of ed visits in the range of 12-24% (5). the characteristics of the elderly, such as unclear complaints, frequent hospital admission, increased cost and more resources used for care, and a higher rate of mortality, are different compared with younger patients (5). particularly in institutionalized patients, up to a quarter of the elderly visit the ed with geriatric syndromes (5, 6). therefore, reaching a diagnosis is challenging for the clinicians because nonspecific clinical manifestations of infection are common in such patients (7). common presentations in the elderly include altered mental status, failure to eat and drink, failure to develop fever, lack of pain, functional decline, reduced mobility, falling, fatigue, and urinary incontinence (8). the absence of fever with a disease that is known to cause fever was the most common atypical presentation (9) and was associated with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and t. hemwej 2 lower rates of ed antibiotic administration and mean intravenous (iv ) fluid volume, and a higher rate of in-hospital mortality (10). many studies reported worse outcomes in delayed antibiotic administration in patients with sepsis and septic shock (1115). the surviving sepsis campaign (ssc) 2018 (16) strongly recommends initiating administration of iv broad-spectrum antibiotics within 1 hour of ed arrival as well as obtaining blood cultures, assessing serum lactate level, and initiating iv fluid resuscitation and early vasopressor treatment. however, according to the infectious diseases society of america (idsa) (17), prescribing aggressive antibiotics and administrating antibiotics over a fixed time period may lead to deleterious consequences. also, some studies and a metaanalysis reported no significant hour-upon-hour increase in sepsis mortality (18-20). moreover, effective use of ssc protocols to administer antibiotics within 1 hour from ed arrival is challenging, especially in elderly patients. therefore, what is the appropriate or suitable time for administration of antibiotics in elderly septic patients in the ed? the aim of this study was to determine whether the time of antibiotic initiation was associated with in-hospital mortality. we also aimed to determine the factors that led to delay in antibiotic initiation. 2. methods 2.1. study design and setting this single-center retrospective cross-sectional study was conducted in elderly septic patients who visited the ed at songklanagarind hospital, which is a tertiary referral and academic hospital on the campus of prince of songkla university in southern thailand. approximately 50,000 patients visit the ed of this hospital each year. patient data from january to december 2019 were retrieved from the hospital electronic medical record database. the research ethics committee of the faculty of medicine, prince of songkla university approved the study (rec 62-425-20-4). 2.2. participants the study enrolled elderly patients (≥65 years) diagnosed with sepsis at the ed according to the songklanagarind hospital sepsis protocol, which was developed from the recommendation of the ssc (16). sepsis is defined as having both a suspected infection and an assessment of physiologic parameters using the national early warning score (news) of ≥5 points. in this study, infection was defined as a demonstrated source of infection or positive culture. the exclusion criteria were no sepsis in final diagnosis, referred patients, and incomplete data (e.g., serum lactate level and culture results). 2.3. data gathering the data obtained from the electronic medical records included clinical presentation, demographic characteristics, emergency severity index (esi) triage level, initial news, laboratory results (complete blood count [cbc], lactate values), treatments (antibiotics, iv fluid, oxygen therapy, mechanical ventilator, vasopressor), sources of infection, ed disposition, length of stay, and hospital outcome. the door-to-antibiotic time was defined as the time from ed arrival to antibiotic initiation. doctor time was the time elapsed until the doctor examined the patient. hemoculture time and cbc time were the times when the nurse took blood samples. the time to receive iv fluids, time to receive vasopressor, time to start mechanical ventilation, and ed disposition time were recorded by the ed nurse. fever was defined as body temperature ≥38°c. 2.4. outcome measurement the primary outcome was the association between the doorto-antibiotic time and in-hospital mortality among elderly patients. the in-hospital mortality rate was calculated in hospitalized sepsis patients. this study also analyzed and compared mortality and door-to-antibiotic time interval as ≤1 hour and each hour interval beyond the first hour. the secondary outcomes were the factors that affected the delay in antibiotic initiation and the most prevalent sources of infection in elderly sepsis patients who visited the ed. 2.5. statistical analysis the n4studies was used to calculate the sample size using a two-tailed test based on a study by tongnoon (21). the final sample size was 534 patients to allow for an expected dropout rate of 10%. continuous data are demonstrated as median with interquartile range (iqr) or mean ± standard deviation. categorical data are presented as number and percentages. the pearson’s chi-squared test was performed on categorical data for the primary outcome. the chi-square test was used for the analysis and to compare mortality and doorto-antibiotic time interval at ≤1 hour and at each hour interval beyond the first hour. after testing associations, selected variables with p-values <0.2 were introduced into a multiple logistic regression model for secondary outcomes. odds ratios (ors) for the outcomes and their 95% confidence intervals (cis) were used to identify the significant factors that led to delay in antibiotic initiation. a two-sided p-value <0.05 was considered statistically significant. all statistical analyses were performed using r software version 3.5.1 (r foundation for statistical computing, vienna, austria). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e44 3. results 3.1. characteristics of the study population the files of 2,208 elderly patients suspected of infection were reviewed. the patients with no sepsis in the final diagnosis, initial news <5 points, referred cases, and charts/files with incomplete data were excluded. the flowchart of the enrollment process is shown in figure 1. a total of 600 patients with the median age of 78.0 (iqr: 72.0-86.0) years were included in the study (50.8% female). the most common sources of infection were pneumonia (38.2%), followed by urinary tract (23.2%), intra-abdominal (16.2%), bacteremia (14.7%), and skin/soft tissue (5.5%). among intra-abdominal infections, acute gastroenteritis (8.3%), acute cholangitis (4.8%), and acute cholecystitis (1.2%) were the most common. ninety-one patients (15.2%) had positive hemocultures for escherichia coli (52.7%), klebsiella pneumoniae (18.7%), staphylococcus spp. (12.1%), and streptococcus spp. (12.1%). frequently prescribed empirical antibiotics were ceftriaxone (64.5%), piperacillin/tazobactam (20.8%), ceftazidime (8%), and carbapenems (4.8%). the percentages of door-to-antibiotic times of ≤1 hour and >1 hour were 59.7% (358/600) and 40.3% (242/600), respectively. table 1 and 2 compared the baseline characters, laboratory findings and outcomes between cases with door to antibiotic time of ≤1 and >1 hour. a comparison between the two groups showed that the ≤1-hour group had a significantly higher esi level and initial news. the median news was 8 points in the ≤1-hour group and 6 points in the >1-hour group. patients in the ≤1-hour group also had more cerebrovascular diseases as co-morbidities and received more vasopressor agents and iv fluids in the ed. patients who complained of fever and higher body temperature (bt), and had a change in the glasgow coma scale score from baseline received antibiotic administration significantly early. patients who complained of gastrointestinal symptoms received antibiotic administration significantly later. 3.2. primary outcomes the median (iqr) door-to-antibiotic time was 51.0 (36.0–89.0) minutes, and the in-hospital mortality rate was 12.5%. there was no significant difference in the median (iqr) door-to-antibiotic times between the discharged patients and those who died in the hospital, 51.0 (36.0–89.0) vs. 54.0 (41.0-85.0); p = 0.382). similarly, there was no significant difference in the in-hospital mortality rate of those with door-to-antibiotic time of ≤1 hour and >1 hour (13.1% vs. 11.6%; p = 0.726). when considering hour-upon-hour of door-to-antibiotic time, no significant difference in the in-hospital mortality rate was observed (p = 0.866). however, the in-hospital mortality rates tended to show a linear increase when each extra hour of door-to-antibiotic time was considered independently. the in-hospital mortality rates of door-to-antibiotic times of 1-2 hours, 2-3 hours, and >3 hours were 10.4%, 11.6%, and 14.6%, respectively (figure 2; p = 0.866). 3.3. secondary outcomes in multivariate analysis, delays in antibiotic initiation of >1 hour were associated with presenting body temperature <38.0°c (or 3.34; 95% ci: 2.12-5.29; p < 0.001) and age <75 years (or 1.70; 95% ci: 1.09-2.64; p = 0.019) (table 3). 4. discussion in this retrospective observational study of elderly patients with sepsis in the ed, door-to-antibiotic time was not associated with in-hospital mortality. sterling et al. (18) found no significant differences when comparing the antibiotic administration within 3 hours from ed triage and within 1 hour from septic shock recognition. door-to-antibiotic time and in-hospital mortality were the main focuses of this study, which showed that each extra hour (relative to door-to-antibiotic time ≤1 hour) was not associated with an increase in the mortality rate. the highest mortality rate in this study was in the door-to-antibiotic group of >3 hours. likewise, peltan et al. (22) found that a door-to-antibiotic time cutoff of 3 hours was associated with mortality, but a cutoff of 1 hour did not show statistical significance. when the door-to-antibiotic times of ≤1 hour and >1 hour were compared, the ≤1-hour group had greater severity of illnesses based on the esi level and news. for this reason, the door-to-antibiotic time of ≤1 hour had a higher mortality rate than the patients who received antibiotics later. the ssc guideline recommends antibiotic initiation within 1 hour. nonetheless, many studies showed failure to achieve that goal. for instance, abe et al. (23) found that 30.5% of cases received antibiotics within 1 hour. ko et al. (24) revealed that the 1-hour target was achieved in 28.6% of septic shock patients treated in the ed. in this study, 59.7% of the patients received antibiotics within 1 hour. the explanation of the differences is that the protocol used to diagnose sepsis was different from the other reports. the median doorto-antibiotic time in this study was 54 minutes, which was shorter than a former report (119 minutes) (25). the reason was a different set of criteria for a diagnosis of sepsis and our standard care followed the hospital policy. overall, the in-hospital mortality rate was 12.5%, which differed from the other studies in elderly patients with sepsis. martin-loeches et al. (26) found that the overall hospital mortality was 48.8% and vardi et al. (27) found a 38.4% mortality rate in patients older than 85 years. the mortality rate in this study was much lower. the explication is that this study collected data in the ed, while the previous studies colthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and t. hemwej 4 lected data in the intensive care unit (icu) where the patients had more severe conditions. atypical presentation accounts for about a third of elderly patients in the ed and a lack of fever is common in the elderly (9). it was found that 29.7% of elderly patients with sepsis have no fever on arrival. henning et al. (10) found that afebrile patients with septic shock in the ed had an increased likelihood of in-hospital mortality compared with febrile patients. similarly, rumbus (28) reported that septic patients with normothermia had a higher mortality rate (31%) compared to those with fever (22%). in this study, no fever (bt <38°c) was an independent factor that led to delay in antibiotic initiation. pneumonia, urinary tract infections, and intra-abdominal infections were found to be the three most common sources of infection in elderly patients. this finding was similar to studies previously reported in thailand (29, 30). emergency physicians should be careful when evaluating the elderly with sepsis by keeping in mind that most elderly patients have atypical presentations. age <75 years, body temperature <38°c, doctor time, and blood sample taking time were significant factors that led to delay in antibiotic initiation. this study showed that door-to-antibiotic time was not associated with in-hospital mortality in elderly sepsis patients. this result supported the idsa recommendation. for sepsis in elderly patients who present with non-specific symptoms or geriatric syndromes, taking time to perform appropriate investigations may be reasonable, because appropriate and smart antibiotic use is an important issue. 5. limitations we acknowledge that this study has several limitations. first, this study was retrospective in nature, which resulted in selection bias; because patients with incomplete data were excluded. second, we could not determine the direct cause and effect, which could subject the study to confounding, and there were uncertain factors that possibly made causal inference between antibiotic time and in-hospital mortality. third, this study used the songklanagarind hospital sepsis protocol and criteria for the diagnosis of sepsis that are probably different from other institutions, which may limit generalizability. fourth, the antibiotic times and in-hospital mortality were not evaluated to arrive at an adjusted severity of sepsis. thus, the findings of this study should be applied with caution in septic shock patients. 6. conclusion door-to-antibiotic time was not associated with in-hospital mortality in elderly sepsis patients in this study. in addition, a linear association between each hour of delay in first antibiotic initiation and in-hospital mortality was not observed. 7. declarations 7.1. acknowledgments the authors are grateful to ms. kingkarn waiyanak for article searches and retrieval, ms. nannapat pruphetkaew, epidemiology unit, faculty of medicine, prince of songkla university for statistical assistance, and glenn k. shingledecker for his help in editing the manuscript. 7.2. funding and support the faculty of medicine, prince of songkla university funded this research. 7.3. author contribution thanaporn hemwej performed the literature search, study design, data collection, data analysis, data interpretation, and wrote the manuscript. siriwimon tantarattanapong did the literature search, study design, critical revision and wrote the manuscript. 7.4. conflict of interest the authors report no conflicts of interest in this work. references 1. prescott hc, angus dc. enhancing recovery from sepsis: a review. jama. 2018;319(1):62-75. 2. fleischmann c, scherag a, adhikari nk, hartog cs, tsaganos t, schlattmann p, et al. assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. american journal of respiratory and critical care medicine. 2016;193(3):259-72. 3. wang he, jones ar, donnelly jp. revised national estimates of emergency department visits for sepsis in the united states. critical care medicine. 2017;45(9):1443. 4. kaukonen k-m, bailey m, suzuki s, pilcher d, bellomo r. mortality related to severe sepsis and septic shock among critically ill patients in australia and new zealand, 20002012. jama. 2014;311(13):1308-16. 5. rutschmann ot, chevalley t, zumwald c, luthy c, vermeulen b, sarasin f. pitfalls in the emergency department triage of frail elderly patients without specific complaints. swiss medical weekly. 2005;135(9-10):145-50. 6. chou m-y, chou s-l, tzeng y-m, chen l-k, yen dh-t, hwang s-j, et al. emergency department (ed) utilization and outcome of oldest old men presenting with geriatric syndromes in a veterans care home in taiwan. archives of gerontology and geriatrics. 2009;49:s32-s6. 7. girard td, ely ew. bacteremia and sepsis in older adults. clinics in geriatric medicine. 2007;23(3):633-47. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e44 8. emmett k. nonspecific and atypical presentation of disease in the older patient. geriatrics (basel, switzerland). 1998;53(2):50-2, 8. 9. limpawattana p, phungoen p, mitsungnern t, laosuangkoon w, tansangworn n. atypical presentations of older adults at the emergency department and associated factors. archives of gerontology and geriatrics. 2016;62:97-102. 10. henning dj, carey jr, oedorf k, day de, redfield cs, huguenel cj, et al. the absence of fever is associated with higher mortality and decreased antibiotic and iv fluid administration in emergency department patients with suspected septic shock. critical care medicine. 2017;45(6):e575-e82. 11. ferrer r, martin-loeches i, phillips g, osborn tm, townsend s, dellinger rp, et al. empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. critical care medicine. 2014;42(8):1749-55. 12. kumar a, roberts d, wood ke, light b, parrillo je, sharma s, et al. duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. critical care medicine. 2006;34(6):1589-96. 13. liu vx, fielding-singh v, greene jd, baker jm, iwashyna tj, bhattacharya j, et al. the timing of early antibiotics and hospital mortality in sepsis. american journal of respiratory and critical care medicine. 2017;196(7):856-63. 14. seymour cw, kahn jm, martin-gill c, callaway cw, yealy dm, scales d, et al. delays from first medical contact to antibiotic administration for sepsis. critical care medicine. 2017;45(5):759. 15. seymour cw, gesten f, prescott hc, friedrich me, iwashyna tj, phillips gs, et al. time to treatment and mortality during mandated emergency care for sepsis. new england journal of medicine. 2017;376(23):2235-44. 16. levy mm, evans le, rhodes a. the surviving sepsis campaign bundle: 2018 update. intensive care medicine. 2018;44(6):925-8. 17. force ist. infectious diseases society of america (idsa) position statement: why idsa did not endorse the surviving sepsis campaign guidelines. clinical infectious diseases. 2018;66(10):1631-5. 18. sterling sa, miller wr, pryor j, puskarich ma, jones ae. the impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. critical care medicine. 2015;43(9):1907. 19. bloos f, thomas-rüddel d, rüddel h, engel c, schwarzkopf d, marshall jc, et al. impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. critical care. 2014;18(2):1-10. 20. puskarich ma, trzeciak s, shapiro ni, arnold rc, horton jm, studnek jr, et al. association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. critical care medicine. 2011;39(9):2066. 21. tongnoon p, srisook n. a retrospective study for the association between the length of stay in an emergency room and the mortality rate among adult sepsis patients in the emergency department of a tertiary care hospital in the south of thailand [dissertation]: songkhla: prince of songkla university; 2020. 22. peltan id, brown sm, bledsoe jr, sorensen j, samore mh, allen tl, et al. ed door-to-antibiotic time and longterm mortality in sepsis. chest. 2019;155(5):938-46. 23. abe t, kushimoto s, tokuda y, phillips gs, rhodes a, sugiyama t, et al. implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in japan: a descriptive analysis of a prospective observational study. critical care. 2019;23(1):1-11. 24. ko bs, choi s-h, shin tg, kim k, jo yh, ryoo sm, et al. impact of 1-hour bundle achievement in septic shock. journal of clinical medicine. 2021;10(3):527. 25. worapratya p, joraluck j, wanjaroenchaisuk a, wuthisuthimethawee p. appropriateness of broad spectrum antibiotics for severe sepsis and septic shock in the emergency department. journal of the medical association of thailand= chotmaihet thangphaet. 2016;99(5):477-83. 26. martin-loeches i, guia mc, vallecoccia ms, suarez d, ibarz m, irazabal m, et al. risk factors for mortality in elderly and very elderly critically ill patients with sepsis: a prospective, observational, multicenter cohort study. annals of intensive care. 2019;9(1):1-9. 27. vardi m, ghanem-zoubi n, bitterman h, abo-helo n, yurin v, weber g, et al. sepsis in nonagenarians admitted to internal medicine departments: a comparative study of outcomes. qjm: an international journal of medicine. 2013;106(3):261-6. 28. rumbus z, matics r, hegyi p, zsiboras c, szabo i, illes a, et al. fever is associated with reduced, hypothermia with increased mortality in septic patients: a meta-analysis of clinical trials. plos one. 2017;12(1):e0170152. 29. ittisanyakorn m, ruchichanantakul s, vanichkulbodee a, sri-on j. prevalence and factors associated with oneyear mortality of infectious diseases among elderly emergency department patients in a middle-income country. bmc infectious diseases. 2019;19(1):1-10. 30. limpawattana p. a secondary analysis of atypical presentations of older patients with infection in the emergency department of a tertiary care hospital in thailand. asian biomed. 2016:181. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and t. hemwej 6 figure 1: flowchart of patients’ enrollment. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e44 figure 2: percentages of in-hospital mortality and door-to-antibiotic time. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. tantarattanapong and t. hemwej 8 table 1: comparing the baseline characteristics between cases with door-to-antibiotic time of ≤ 1 and > 1 hour characteristics door-to-antibiotic time (hour) p-value ≤1 (n=358) >1 (n=242) age (year) 80.0 (73.086.0) 77.0 (70.0-84.0) 0.014 gender female 176 (49.2) 129 (53.3) 0.361 male 182 (50.8) 113 (46.7) esi levels 1 67 (18.7)) 32 (13.2) <0.001 2 264 (73.7) 143 (59.1) 3 25 (7.0) 66 (27.3) 4 2 (0.6) 1 (0.4) co-morbidities diabetes mellitus 127 (35.5) 73 (30.2) 0.206 hypertension 180 (50.3) 122 (50.4) 1.000 chronic kidney disease 54 (15.1) 37 (15.3) 1.000 cerebrovascular disease 115 (32.1) 51 (21.1) 0.004 heart disease 77 (21.5) 54 (22.3) 0.894 respiratory disease 57 (15.9) 51 (21.1) 0.133 malignancy 85 (23.7) 52 (21.5) 0.585 medication use systemic steroid 30 (8.4) 14 (5.8) 0.300 immunosuppressive agents 4 (1.1) 5 (2.1) 0.496 chemotherapy (within 1 month) 23 (6.4) 15 (6.2) 1.000 beta blocker 76 (21.2) 41 (16.9) 0.232 bronchodilator 43 (12.0) 32 (13.2) 0.753 central acting agents 53 (14.8) 33 (13.6) 0.778 psychotropic medication 25 (7.0) 15 (6.2) 0.833 opioids 16 (4.5) 7 (2.9) 0.441 chief complaint fever 180 (50.3) 98 (40.5) 0.023 respiratory tract symptoms 91 (25.4) 62 (25.6) 1.000 drowsy, stupor, coma 35 (9.8) 26 (10.7) 0.805 gastrointestinal symptoms 33 (9.2) 41 (16.9) 0.007 fatigue 12 (3.4) 6 (2.5) 0.711 fall 3 (0.8) 2 (0.8) 1.000 presenting vital signs body temperature (°c) 38.5 (38.0-39.1) 38.1 (37.0-38.8) <0.001 pulse rate (/ minute) 108.3 ± 20.7 106.0 ± 18.2 0.160 systolic blood pressure (mmhg) 135.5 ± 31.8 135.4 ± 28.6 0.951 respiratory rate (/minute) 32.0 (28.0-36.0) 30.0 (26.0-36.0) 0.019 gcs change from baseline 89 (24.9) 41 (16.9) 0.027 initial news 8 (6-10) 6 (5-8) <0.001 data are presented as n (%), mean ± standard deviation or median and interquartile range (iqr). esi: emergency severity index; gcs: glasgow coma scale; news: national early warning score. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e44 table 2: comparing the laboratory findings and outcomes between cases with door-to-antibiotic time of ≤ 1 and > 1 hour characteristics door-to-antibiotic time p-value ≤1 hour(n=358) >1 hour(n=358) ed laboratory findings wbc (1,000/dl) 11.6 (8.2-16.1) 11.4 (8.1-15.9) 0.973 pmn (%) 82.0 (73.3-88) 83.4 (74.8-89.0) 0.087 band cells (%) 6.0 (2.0-13.0) 3.0 (1.0-11.0) 0.013 lactate ≥2 mmol/l 145.0 (44.5) 73.0 (38.8) 0.248 ed treatment vasopressor 34 (9.5) 11 (4.5) 0.036 iv fluid replacement 298 (83.2) 162 (66.9) <0.001 ed length of stay (minute) 265.0 (211.5-350.8) 290.5 (218-369.8) 0.133 ed disposition 0.171 intensive care unit 30 (8.4) 16 (6.6) ward 213 (59.5) 125 (51.7) short-stay observation unit 55 (15.4) 49 (20.2) discharge 59 (16.5) 50 (20.7) death in ed 1 (0.3) 2 (0.8) outcome of admission discharge 259 (86.9) 168 (88.4) 0.726 death 39 (13.1) 22 (11.6) hospitalization (days) 7.0 (3.0–14.0) 6.5 (3.0-11.8) 0.090 time door-to-doctor time (minute) 3.0 (0.0–7.0) 6.0 (2.0-14.0) <0.001 door-to-cbc time (minute) 29.0 (18.2-38.8) 44.0 (29.0–65.0) <0.001 door-to-lactate time (minute) 19.0 (10.0 -36.0) 36.0 (16.5-83.0) <0.001 data are presented as n (%), mean ± standard deviation or median and interquartile range (iqr). ed: emergency department; wbc: white blood cell; pmn: polymorphic neutrophils; iv: intravenous; cbc: complete blood count. table 3: multiple logistic regression analysis of factors that led to a delay in antibiotic initiation (>1 hour) variables adjusted or 95% ci p-value no fever (bt <38°c) 3.34 2.12 5.29 <0.001 age <75 years 1.70 1.09 2.64 0.019 door-to-doctor time 1.04 1.01 1.06 0.002 door-to-cbc time 1.04 1.03 1.05 <0.001 door-to-lactate time 1.01 1.00 1.01 0.006 or: odds ratio; ci: confidence interval; bt: body temperature; cbc: complete blood count. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e51 rev i ew art i c l e premature coronary artery disease and plasma levels of interleukins; a systematic scoping review and metaanalysis mohammad haji aghajani1,2, amirmohammad toloui3, koohyar ahmadzadeh3, arian madani neishaboori3∗, mahmoud yousefifard4,3 † 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of cardiology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. physiology research center, iran university of medical sciences, tehran, iran. 4. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: march 2022; accepted: may 2022; published online: 27 june 2022 abstract: introduction: interleukins (ils) can act as a predictive indicator of premature coronary artery disease (pcad) and may be useful in screening of high-risk patients. however, there is no consensus on the relationship of serum levels of ils and pcad, yet. as a result, this study has been conducted in order to review the literature on the relationship between serum levels of different ils and pcad. methods: medline, scopus, embase, and web of science databases were searched until december 7th 2020. two reviewers independently screened and summarized eligible articles. a meta-analysis was performed to assess the relationship of ils and pcad. results: 12 case-control articles were included. il-6 plasma changes do happen in pcad patients with a standardized mean difference (smd) of 0.51 (95% ci: 0.12-0.90; p=0.010) compared with the control group. this difference was also observed when evaluating the plasma levels of il-1 and il-17, with an smd of 1.42 (95% ci: 1.111.73; p<0.001) and 0.59 (95% ci: 0.14-1.04; p=0.011), respectively. meanwhile, no significant difference existed in plasma levels of il-10 (smd=0.26; 95% ci: -0.17-0.70; p=0.236), and il-18 (smd=1.44; 95% ci: -0.19-3.07; p=0.083) between pcad patients and those in the control group. conclusion: low level of evidence showed that there may be a significant relationship between increased plasma levels of ils and the occurrence of pcad. as a result, prospective cohort studies with serial assessments of serum ils during follow up period, focusing on controlling classical risk factors of pcad and increase in level of ils, should be conducted. keywords: coronary artery disease; cardiovascular disease; interleukins; prognosis; biomarkers cite this article as: haji aghajani m, toloui a, ahmadzadeh k, madani neishaboori a, yousefifard m. premature coronary artery disease and plasma levels of interleukins; a systematic scoping review and meta-analysis. arch acad emerg med. 2022; 10(1): e51. https://doi.org/10.22037/aaem.v10i1.1605. 1. introduction coronary artery disease (cad) is a condition in which buildup of atherosclerotic plaques leads to narrowing of the coronary arteries. this disease manifests in various clinical ∗corresponding author: arian madani neishaboori, physiology research center, school of medicine, iran university of medical sciences, shahid hemmat highway, tehran 14496-14535, iran. tel: +98 (21) 86704771; email: arian.md7@gmail.com, orcid: http://orcid.org/0000-0002-1920-9299. † corresponding author: mahmoud yousefifard; pediatric chronic kidney disease research center, tehran university of medical sciences, children’s medical center, gharib st., tehran, iran. tel: +98 (21) 86704771; email: yousefifard.m@iums.ac.ir, orcid: http://orcid.org/0000-0001-5181-4985. forms, including angina and myocardial infarction (mi). cad is the leading cause of death worldwide (1, 2), having a prevalence of 6.7% (18.2 million individuals) amongst people aged 20 years or older, with one individual having an mi every 40 seconds in us (3). given its importance and profound burden on the society, identifying its risk factors and managing them could play a key role in helping affected patients. furthermore, coronary artery disease can occur in younger ages, which is named premature coronary artery disease (pcad). in particular, it has a cut off age, mostly suggested to be less than 55 and 65 years for men and women, respectively (4). although most studies suggest a low incidence rate for pcad, it is possible that with the rise in cardiovascular risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 2 factors, such as smoking and obesity, among younger population, the number of young individuals with underlying conditions that may lead to pcad is much higher than currently estimated (5). in addition, because of the devastating effects of this disease on the more active lifestyle of young patients, and also the importance of early detection and treatment of young individuals, prompt and accurate identification of young individuals who are at the greatest risk is necessary (6). pcad is defined as an inflammatory disease (7), and cardiovascular events are more common in patients with high circulating levels of several inflammatory markers. in this regard, treating patients based on inflammatory parameters, such as hs-c reactive protein (hs-crp), has been proved to improve outcomes (8). on the other hand, interleukins (ils) are a group of cytokines with important roles in the regulation of immune and inflammatory responses. several ils (such as il-1 and il-6) are major players at the downstream of vascular inflammatory cascades (9). as it has been shown in several studies, there might be a relationship between serum level of different types of ils (il-1, il-6, etc.) and coronary artery diseases (10-12). since other inflammatory cytokines such as hs-c reactive protein have been classically linked to coronary events, it is also reasonable to study the possible relationship between ils and coronary events. therefore, ils can serve as a predictive indicator of pcad and may be useful in screening of high-risk patients. however, there is no consensus on the relationship of serum levels of ils and pcad, yet. as a result, this study has been conducted in order to review the literature on the relationship between serum levels of different ils and pcad. 2. methods 2.1. study design and search strategy the current systematic review and meta-analysis is designed for the aim of investigating the changes in the plasma level of different types of ils following a coronary artery disease in the younger population, or pcad as previously defined. accordingly, pico was defined as follows: patients (p): male patients younger than 55 and female patients younger than 65 years of age, with angiographically confirmed coronary artery stenosis more than 50% in coronary vessels. index test (i): measuring plasma level of ils in patients. comparison (c): comparing results of the case group (with the defined coronary artery stenosis) with those of the control group (patients without the defined coronary artery stenosis). outcome (o): occurrence of pcad. for this purpose, medline (via pubmed), scopus, embase, and web of science databases were thoroughly searched using carefully selected keywords. these keywords were selected using mesh and emtree vocabularies, reviewing similar articles’ relevant keywords, and with the help of experts in the field. then, a systematic search strategy was designed based on the defined p and i and using the selected keywords. this search was initially performed for articles published until november 6th, 2020, and then updated until december 7th 2020. the search strategy in medline database is presented in appendix 1. in addition, a manual search was also performed in google and google scholar to obtain any preprints and possibly missing papers. 2.2. selection criteria the inclusion criteria in the present systematic review were reporting plasma levels of ils, independently in case and control groups, and conducting the research on a population of pcad patients, regardless of their underlying condition. the exclusion criteria consisted of not having a control group, case report studies, and review articles. 2.3. data collection two reviewers independently screened titles and abstracts of the retrieved articles, for inclusion based on the inclusion criteria. then, eligible articles were obtained and exclusion criteria were applied to select the included articles. finally, a summary of the included articles’ data was recorded using a checklist, consisting of the following variables: first author’s name, publication year, country in which the study was conducted, study design, definition of the pcad patients, number of patients in case group, number of patients in the control group, mean age of the patients in the case group, mean age of the patients in the control group, type of the measured ils, plasma level of the ils in the case group, plasma level of the ils in the control group, and the time interval between angiography and measurement of ils levels in patients’ plasma sample. any disagreement between the reviewers was resolved via discussion with a third reviewer. 2.4. quality assessment two independent reviewers performed the quality assessments using national heart, lung, and blood institute (nhlbi) quality assessment tools for case-control studies (13). any disagreement was resolved through discussion with a third reviewer. 2.5. statistical analysis all analyses were performed using stata 14.0 statistical program. data were recorded as mean and standard deviation (sd) in case and control groups, separately. then using “metan” command in stata program a standardized mean difference (smd) was calculated for each individual study. finally, a pooled smd and 95% confidence interval (95% ci) was reported. heterogeneity among studies was assessed, using i2 test. egger’s test and funnel plot were used to assess publication bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e51 3. results 3.1. study characteristics the systematic search in the electronic databases yielded 622 records. 269 duplicates were eliminated and 353 articles remained. afterwards, reviewers performed the initial screening according to the inclusion criteria, gathering 44 articles were found to be potentially eligible to enter the current study. then, applying the exclusion criteria, the next screening process was performed, resulting in the inclusion of 12 articles (all of them had case-control design) in the present systematic review and meta-analysis (figure 1) (14-25), three of which measured more than one type of ils in the studied patients (14, 15, 19). il-6 was measured in seven studies (1417, 20, 21, 24), il-10 was measured in four studies (14, 19, 22, 25), il-18 was measured in three studies (14, 19, 23) and il-1 (15) and il-17 (18) were each measured in one study. overall, 3098 patients with pcad and 3711 control subjects were studied in the included articles. among them, 2696 of the pcad patients and 2271 of control patients were male. these studies had taken place in various countries: pakistan (14, 19), greece (15), india (16), south korea (17), turkey (18), south africa (21), sweden (20), mexico (22), australia (23), poland (24), and china (25). regarding the design of the included studies, seven studies were conducted prospectively (14, 15, 18, 19, 21, 24, 25) and the other five were conducted retrospectively (16, 17, 20, 22, 23). all of the included studies confirmed pcad performing a coronary angiography. detailed characteristics of the articles is summarized in table 1. 3.2. risk of bias assessment sample size justification, blinding of the assessors, adjustment of the results based on key confounding variables, and the use of concurrent controls were not recorded in any of the studies. also, none of the study samples were randomly taken from their target population. table 2 presents details of risk of bias assessment among the included studies. 3.3. publication bias publication bias was assessed regarding the report of the case and control groups’ plasma levels of il-6, il-10 and il18, while il-17 and il-1 were separately measured in only one article each. as depicted on figure 2, no publication bias exists regarding the assessment of il-6 (p=0.440), il-10 (p=0.960), and il-18 (p=0.181) in the pcad patients. 3.4. meta-analysis the differences in the plasma levels of ils between pcad patients and control patients were evaluated, and the results are depicted in figure 3. it was shown that il-6 plasma changes do happen in pcad patients with a standardized mean difference (smd) of 0.51 (95% ci: 0.12 to 0.90; p = 0.010) compared with the control group. this difference was also observed when evaluating the plasma levels of il-1 and il-17, with an smd of 1.42 (95% ci: 1.11 to 1.73; p < 0.001) and 0.59 (95% ci: 0.14 to 1.04; p = 0.011), respectively. meanwhile, no significant difference existed in plasma levels of il-10 (smd=0.26; 95% ci: -0.17 to 0.70; p =0.236), and il-18 (smd=1.44; 95% ci: -0.19 to 3.07; p = 0.083) between pcad patients and the control group. however, the i2 test revealed a considerable amount of heterogeneity among the studies. 4. discussion the present systematic review and meta-analysis evaluated the changes of the plasma levels of different types of ils following pcad. for this purpose, il plasma levels were compared between the pcad patients and the participants in the control groups in the included studies. as mentioned above, an explicit correlation exists between the occurrence of pcad and the plasma levels of il-6, il-1 and il-17. as a result, it can be concluded that in pcad patients, a rise in the plasma levels of the three ils will possibly be observed. however, the heterogeneity among the studies was considerably high, making it tough to firmly conclude on the exact correlation between il plasma levels and the occurrence of pcad. moreover, the existing literature regarding this subject is also controversial. for instance, satti et al. reports that increased plasma levels of il-6 is associated with higher risk of cad (26), while ghazouani et. al reports no correlation between cad and il-6 (27), while in both studies, pcad patients were present among the study population. overall, these heterogeneities in the studies can be attributed to many factors. firstly, none of the studies included in our group of eligible articles reported their results with respect to coronary risk factors, for example diabetes, lipid profile, smoking status, existence of hypertension and etc., which were present in their study populations. these risk factors could result in different amounts of change in il plasma levels. thus, we do recommend that in future studies, these risk factors be carefully evaluated and matched between the case and the control groups. secondly, the time interval between il measurement and the occurrence of pcad was somewhat vague in the studies. as a result, il plasma levels could change in time following a coronary event in patients. with respect to the definitions of pcad patient not being exactly the same between the included studies, this limitation could be overturned by adopting exactly similar definitions regarding the occurrence of pcad and, accordingly calculating the time interval between the coronary event and the measurement of il’s plasma level. in addition, all included studies had case-control design and there were no prospective cohort studies. therefore, the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 4 overall level of evidence in the present meta-analysis is low. 5. conclusion low level of evidence showed that there may be a significant relationship between plasma levels of ils and the occurrence of pcad. since, there were no prospective cohort studies, included in the present meta-analysis, the screening value of ils in prediction of pcad is not clear. as a result, prospective cohort studies with serial assessments of serum ils during follow up period, focusing on controlling classical risk factors of pcad and increase in level of ils, should be conducted, with respect to the mentioned limitations, to resolve this uncertainty. 6. declarations 6.1. acknowledgments none. 6.2. availability of data and materials all data generated or analyzed during this study are included in this published article. 6.3. authors’ contributions study design: my, mha performing search and designing search strategy: all authors. data gathering and quality assessment of included studies: ka, amn, at, mha analysis: my drafting: amn, at, ka, my critically revised: my and mha 6.4. funding and supports prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 6.5. conflict of interest there is no conflict of interest. 6.6. role of the sponsor the prevention of cardiovascular disease research center, shahid beheshti university of medical sciences had no role in the design and conduct of the study; collection, management, and analysis of the data. references 1. anthony d, george p, eaton cb. cardiac risk factors: environmental, sociodemographic, and behavioral cardiovascular risk factors. fp essent. 2014;421:16-20. 2. williams ra. cardiovascular disease in african american women: a health care disparities issue. j natl med assoc. 2009;101(6):536-40. 3. virani ss, alonso a, benjamin ej, bittencourt ms, callaway cw, carson ap, et al. heart disease and stroke statistics—2020 update: a report from the american heart association. circulation. 2020:e139-e596. 4. fihn sd, gardin jm, abrams j, berra k, blankenship jc, dallas ap, et al. 2012 accf/aha/acp/aats/pcna/scai/sts guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the american college of cardiology foundation/american heart association task force on practice guidelines, and the american college of physicians, american association for thoracic surgery, preventive cardiovascular nurses association, society for cardiovascular angiography and interventions, and society of thoracic surgeons. j am coll cardiol. 2012;60(24):e44-e164. 5. mates j, mademont-soler i, fernandez-falgueras a, sarquella-brugada g, cesar s, arbelo e, et al. sudden cardiac death and copy number variants: what do we know after 10 years of genetic analysis? forensic sci int genet. 2020;47:102281. 6. angelantonio ed, butterworth as. clinical utility of genetic variants for cardiovascular risk prediction. circ cardiovasc genet. 2012;5(4):387-90. 7. tousoulis d, charakida m, stefanadis c. endothelial function and inflammation in coronary artery disease. postgrad med j. 2008;84(993):368-71. 8. ridker pm, danielson e, fonseca fa, genest j, gotto jr am, kastelein jj, et al. rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. n engl j med. 2008;359(21):2195-207. 9. sattar n, mccarey dw, capell h, mcinnes ib. explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. circulation. 2003;108(24):2957-63. 10. bacchiega bc, bacchiega ab, usnayo mjg, bedirian r, singh g, pinheiro gdrc. interleukin 6 inhibition and coronary artery disease in a high-risk population: a prospective community-based clinical study. j am heart assoc. 2017;6(3):e005038. 11. szekely y, arbel y. a review of interleukin-1 in heart disease: where do we stand today? cardiol ther. 2018;7(1):25-44. 12. wainstein mv, mossmann m, araujo gn, gonçalves sc, gravina gl, sangalli m, et al. elevated serum interleukin6 is predictive of coronary artery disease in intermediate risk overweight patients referred for coronary angiography. diabetol metab syndr. 2017;9(1):1-7. 13. health nio. study quality assessment tools| national this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e51 heart, lung, and blood institute (nhlbi) united states: national institutes of health; 2014 [available from: https://www.nhlbi.nih.gov/health-topics/studyquality-assessment-tools. 14. ansari wm, humphries se, naveed ak, khan oj, khan da, khattak eh. effect of coronary artery disease risk snps on serum cytokine levels and cytokine imbalance in premature coronary artery disease. cytokine. 2019;122:154060. 15. antoniades c, tousoulis d, vasiliadou c, pitsavos c, chrysochoou c, panagiotakos d, et al. genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction. j am coll cardiol. 2005;46(6):1101-9. 16. ghatge m, sharma a, vangala rk. association of yglutamyl transferase with premature coronary artery disease. biomed rep. 2016;4(3):307-12. 17. cho s, hak lee s, park s, ha jee s, ki hong m, chung n, et al. the additive value of multiple biomarkers in prediction of premature coronary artery disease. acta cardiol. 2015;70(2):205-10. 18. demir b, ünğan i̇, oflar e, khankishiyev v, pirhan o, demir e, et al. elevated serum interleukin 17a level in patients with premature acute coronary syndrome. turkiye klinikleri cardiovasc sci. 2015;27(2):53-60. 19. khan da, ansari wm, khan fa. pro/anti-inflammatory cytokines in the pathogenesis of premature coronary artery disease. j interferon cytokine res. 2011;31(7):5617. 20. lundman p, boquist s, samnegard a, bennermo m, held c, ericsson c-g, et al. a high-fat meal is accompanied by increased plasma interleukin-6 concentrations. nutr metab cardiovasc dis. 2007;17(3):195-202. 21. phulukdaree a, khan s, ramkaran p, govender r, moodley d, chuturgoon aa. the interleukin-6147 g/c polymorphism is associated with increased risk of coronary artery disease in young south african indian men. metab syndr relat disord. 2013;11(3):205-9. 22. posadas-sánchez r, angeles-martínez j, pérezhernández n, rodríguez-pérez jm, lópez-bautista f, flores-dominguez c, et al. the il-10-1082 (rs1800896) g allele is associated with a decreased risk of developing premature coronary artery disease and some il-10 polymorphisms were associated with clinical and metabolic parameters. the gea study. cytokine. 2018;106:12-8. 23. thompson sr, mccaskie pa, beilby jp, hung j, jennens m, chapman c, et al. il18 haplotypes are associated with serum il-18 concentrations in a population-based study and a cohort of individuals with premature coronary heart disease. clin chem. 2007;53(12):2078-85. 24. pauli n, puchałowicz k, kuligowska a, krzystolik a, dziedziejko v, safranow k, et al. associations between il6 and echo-parameters in patients with early onset coronary artery disease. diagnostics. 2019;9(4):189. 25. wang y, yu x, wang p, bao z. interleukin 10 gene627 polymorphisms in chinese patients with early-onset coronary heart disease. zhonghua yi xue yi chuan xue za zhi. 2005;22(6):679-81. 26. satti hs, hussain s, javed q. association of interleukin6 gene promoter polymorphism with coronary artery disease in pakistani families. scientificworldjournal. 2013;2013:538365. 27. ghazouani l, abboud n, khalifa sbh, added f, khalfallah ab, nsiri b, et al. -174g> c interleukin-6 gene polymorphism in tunisian patients with coronary artery disease. ann saudi med. 2011;31(1):40-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 6 figure 1: flow diagram of the present meta-analysis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e51 figure 2: funnel plot for the analysis of publication bias regarding the correlation between the occurrence of premature coronary artery disease and the changes in the plasma level of interleukins (ils). no publication bias was observed for il-6 (p=0.440), il-10 (p=0.960) and il-18 (p=0.181). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 8 figure 3: forest plot for the assessment of the changes in the plasma levels of interleukins (ils) in premature coronary artery disease (pcad) patients compared with that of the control group. smd: standardized mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e51 table 1: summary and characteristics of the included studies author; year; country study design definition of pcad in the study no. of patients in the case group no. of patients in the control group mean age of patients in the case group mean age of patients in the control group no. of males in the case group no. of males in the control group type of il time interval between angiography and il measurement (hours) il plasma level in the case group il plasma level in the control group unit il-18 0 236.6± 42.5 175.6±21.8 pg/ml ansari; 2017; pakistan prospective >70% stenosis in at least one coronary vessel & age<45 329 310 42 39 329 298 il-6 3.8± 1.5 2.9±1.9 ng/dl il-10 0.83± 0.53 0.87±0.36 pg/ml antoniades; 2005; greek prospective st segment elevation mi & age<49 58 205 48.6 49.7 58 180 il-1b 24 1.37± 1.41 0.31±0.37 pg/ml il-6 7.7±4.3 2.16±2.15 pg/m ghatge; 2016; india retrospective >70% stenosis in at least one coronary vessel & age<45 in males or age<50 in females 93 120 41.79 41.78 93 93 il-6 12 3.66± 0.19 2.98±0.15 pg/ml cho; 2015; korea retrospective >50% stenosis in at least two coronary vessels & age<55 in males or age<60 in females 414 503 49.3 48.6 414 414 il-6 nr 9.6±44.1 3.6±8.9 pg/ml demir; 2015; turkey prospective angiography confirmed coronary artery disease & age<45 45 35 39.6 40.1 35 19 il-17a 12 2 ± 1.88 0.9±1.86 pg/ml il-18 0 302.25±114.81 145±88.89 pg/ml khan; 2011; pakistan prospective >70% stenosis in at least one coronary vessel & age<45 98 74 40 35 89 65 il-10 2.03±1.7 1.63±1.85 pg/ml ludman; 2007; sweden retrospective myocardial infarction and age between 45-55 41 26 51 51 41 26 il-6 nr 3.7± 2.28 3.81±3.49 ng/dl phulukdare; 2013; south africa prospective angiography confirmed coronary artery disease & age<45 41 61 nr nr 41 61 il-6 nr 0.91±0.01 0.86±0.13 pg/ml this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 10 table 1: summary and characteristics of the included studies author; year; country study design definition of pcad in the study no. of patients in the case group no. of patients in the control group mean age of patients in the case group mean age of patients in the control group no. of males in the case group no. of males in the control group type of il time interval between angiography and il measurement (hours) il plasma level in the case group il plasma level in the control group unit posadassanchez; 2018; mexico retrospective infarction or >50% stenosis in coronary vessel & age<55 in males and age<65 in females 1160 1106 54 51 940 455 il-10 nr 1.01±0.83 0.53±0.55 pg/ml thompson; 2007; australia retrospective >50% stenosis in at least one coronary vessel & age<60 556 1109 50 53 487 558 il-18 nr 366.2±156 327.8±146.6 pg/ml pauli; 2019; poland prospective angiography confirmed coronary artery disease & age<55 in males and age<60 in females 100 50 49.9 48 75 37 il-6 12 1.69±2.77 1.47±0.33 pg/ml wang; 2005; china prospective infarction or >50% stenosis in coronary vessel & age<55 in males and age<65 in females 163 112 51 49 94 65 il-10 nr 33.28±11.26 30.83±10.07 pg/ml pcad: premature coronary artery disease; il: interleukin. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e51 table 2: risk of bias assessment of the included studies author; year items 1 2 3 4 5 6 7 8 9 10 11 12 ansari; 2017 yes yes no yes yes yes na nr yes yes nr no antoniades; 2005 yes yes no yes yes yes na nr yes yes nr no ghatge; 2016 yes yes no yes nr yes na nr yes yes nr no cho; 2015 yes yes no yes yes yes na nr yes yes nr no demir; 2015 yes yes no yes yes yes na nr yes yes nr no khan; 2011 yes yes no yes yes yes na nr yes yes nr no ludman; 2007 yes yes no yes yes yes na nr yes yes nr no phulukdaree; 2013 nr no no yes yes yes na nr yes yes nr no posadas-sanchez; 2018 yes yes no yes yes yes na nr yes yes nr no thompson; 2007 yes yes no no yes yes na nr yes yes nr no pauli; 2019 yes yes no yes yes yes yes nr yes yes nr no wang; 2005 yes yes no yes yes yes na nr yes yes nr no na: not applicable; nr: not reported. items: 1. was the research question or objective in this paper clearly stated and appropriate? 2. was the study population clearly specified and defined? 3. did the authors include a sample size justification? 4. were controls selected or recruited from the same or similar population that gave rise to the cases (including the same timeframe)? 5. were the definitions, inclusion and exclusion criteria, algorithms or processes used to identify or select cases and controls valid, reliable, and implemented consistently across all study participants? 6. were the cases clearly defined and differentiated from controls? 7. if less than 100 percent of eligible cases and/or controls were selected for the study, were the cases and/or controls randomly selected from those eligible? 8. was there use of concurrent controls? 9. were the investigators able to confirm that the exposure/risk occurred prior to the development of the condition or event that defined a participant as a case? 10. were the measures of exposure/risk clearly defined, valid, reliable, and implemented consistently (including the same time period) across all study participants 11. were the assessors of exposure/risk blinded to the case or control status of participants? 12. were key potential confounding variables measured and adjusted statistically in the analyses? if matching was used, did the investigators account for matching during study analysis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 12 appendix 1: medline search query search terms 1. “coronary artery disease” [mh] or “myocardial infarction” [mh] or “myocardial ischemia” [mh] or “acute coronary syndrome” [mh] or “coronary stenosis” [mh] or “st elevation myocardial infarction” [mh] or “non-st elevated myocardial infarction” [mh] or premature cad[tiab] or premature coronary artery disease[tiab] or coronary artery disease[tiab] or artery disease, coronary[tiab] or artery diseases, coronary[tiab] or coronary artery diseases[tiab] or disease, coronary artery[tiab] or diseases, coronary artery[tiab] or coronary arteriosclerosis[tiab] or arterioscleroses, coronary[tiab] or coronary arterioscleroses[tiab] or atherosclerosis, coronary[tiab] or atheroscleroses, coronary[tiab] or coronary atheroscleroses[tiab] or coronary atherosclerosis[tiab] or arteriosclerosis, coronary[tiab] or myocardial infarction[tiab] or infarction, myocardial[tiab] or infarctions, myocardial[tiab] or myocardial infarctions[tiab] or cardiovascular stroke[tiab] or cardiovascular strokes[tiab] or stroke, cardiovascular[tiab] or strokes, cardiovascular[tiab] or myocardial infarct[tiab] or infarct, myocardial[tiab] or infarcts, myocardial[tiab] or myocardial infarcts[tiab] or heart attack[tiab] or heart attacks[tiab] or myocardial ischemia[tiab] or ischemia, myocardial[tiab] or ischemias, myocardial[tiab] or myocardial ischemias[tiab] or ischemic heart disease[tiab] or heart disease, ischemic[tiab] or disease, ischemic heart[tiab] or diseases, ischemic heart[tiab] or heart diseases, ischemic[tiab] or ischemic heart diseases[tiab] or acute coronary syndrome[tiab] or acute coronary syndromes[tiab] or coronary syndrome, acute[tiab] or coronary syndromes, acute[tiab] or syndrome, acute coronary[tiab] or syndromes, acute coronary[tiab] or premature heart attack[tiab] or coronary stenosis[tiab] or stenoses, coronary[tiab] or stenosis, coronary[tiab] or coronary artery stenosis[tiab] or artery stenoses, coronary[tiab] or artery stenosis, coronary[tiab] or coronary artery stenoses[tiab] or stenoses, coronary artery[tiab] or stenosis, coronary artery[tiab] or coronary stenoses[tiab] or st elevation myocardial infarction[tiab] or st segment elevation myocardial infarction[tiab] or st elevated myocardial infarction[tiab] or stemi[tiab] or non-st elevated myocardial infarction[tiab] or non st elevated myocardial infarction[tiab] or nstemi[tiab] or non-st-elevation myocardial infarction[tiab] or infarction, non-st-elevation myocardial[tiab] or infarctions, non-st-elevation myocardial[tiab] or myocardial infarction, non-st-elevation[tiab] or myocardial infarctions, non-stelevation[tiab] or non st elevation myocardial infarction[tiab] or non-st-elevation myocardial infarctions[tiab] 2. premature[tiab] or early onset[tiab] 3. “interleukin-1”[mh] or “interleukin-1alpha”[mh] or “interleukin-1beta”[mh] or “interleukin-10”[mh] or “interleukin-11”[mh] or “interleukin-12”[mh] or “interleukin-12 subunit p35”[mh] or “interleukin-12 subunit p40”[mh] or “interleukin-13”[mh] or “interleukin-15”[mh] or “interleukin-16”[mh] or “interleukin-17”[mh] or “interleukin-18”[mh] or “interleukin-2”[mh] or “interleukin-23”[mh] or “interleukin-12 subunit p40”[mh] or “interleukin-23 subunit p19”[mh] or “interleukin-27”[mh] or “interleukin-3”[mh] or “interleukin-33”[mh] or “interleukin-4”[mh] or “interleukin-5”[mh] or “interleukin-6”[mh] or “interleukin-7”[mh] or “interleukin-8”[mh] or “interleukin-9”[mh] or interleukins[tiab] or interleukin[tiab] or interleukin1[tiab] or interleukin 1[tiab] or il-1[tiab] or t helper factor[tiab] or lymphocyte-activating factor[tiab] or lymphocyte activating factor[tiab] or macrophage cell factor[tiab] or epidermal cell derived thymocyte-activating factor[tiab] or epidermal cell derived thymocyte activating factor[tiab] or interleukin i[tiab] or interleukin-1alpha[tiab] or interleukin 1alpha[tiab] or il-1 alpha[tiab] or interleukin-1 alpha[tiab] or interleukin 1 alpha[tiab] or hematopoietin-1[tiab] or hematopoietin 1[tiab] or interleukin-1beta[tiab] or interleukin 1beta[tiab] or il-1 beta[tiab] or interleukin-1 beta[tiab] or interleukin 1 beta[tiab] or catabolin[tiab] or interleukin-10[tiab] or interleukin 10[tiab] or il10[tiab] or il-10[tiab] or csif-10[tiab] or cytokine synthesis inhibitory factor[tiab] or interleukin-11[tiab] or interleukin 11[tiab] or il-11[tiab] or il11[tiab] or adipogenesis inhibitory factor[tiab] or factor, adipogenesis inhibitory[tiab] or inhibitory factor, adipogenesis[tiab] or interleukin-12[tiab] or natural killer cell stimulatory factor[tiab] or il-12[tiab] or cytotoxic lymphocyte maturation factor[tiab] or il 12[tiab] or il-12 p70[tiab] or interleukin-12 p70[tiab] or interleukin 12 p70[tiab] or interleukin 12[tiab] or il12[tiab] or edodekin alfa[tiab] or interleukin-13[tiab] or il-13[tiab] or interleukin 13[tiab] or il 13[tiab] or il13[tiab] or interleukin-15[tiab] or il15[tiab] or interleukin 15[tiab] or il-15[tiab] or interleukin-16[tiab] or interleukin 16[tiab] or il16[tiab] or lymphocyte chemoattractant factor[tiab] or chemoattractant factor, lymphocyte[tiab] or il-16[tiab] or lcf factor[tiab] or interleukin-17[tiab] or interleukin 17[tiab] or ctla-8[tiab] or il-17[tiab] or interleukin-17f[tiab] or interleukin 17f[tiab] or il-17f[tiab] or cytokine ml-1[tiab] or cytokine ml 1[tiab] or interleukin-17c[tiab] or interleukin 17c[tiab] or il-17c[tiab] or cytokine cx2[tiab] or cx2, cytokine[tiab] or interleukin-17e[tiab] or interleukin 17e[tiab] or interleukin-25[tiab] or interleukin 25[tiab] or il-17e[tiab] or il 17e[tiab] or interleukin-17a[tiab] or interleukin 17a[tiab] or cytotoxic t lymphocyte-associated antigen 8[tiab] or cytotoxic t lymphocyte associated antigen 8[tiab] or il-17a[tiab] or ctla8[tiab] or interleukin-17b[tiab] or interleukin 17b[tiab] or il-17b[tiab] or interleukin-18[tiab] or interleukin 18[tiab] or ifn-gamma-inducing factor[tiab] or il-18[tiab] or interferon-gamma inducing factor[tiab] or inducing factor, interferon-gamma[tiab] or interferon gamma inducing factor[tiab] or interferon-gamma-inducing factor[tiab] or ifn-gamma inducing factor[tiab] or ifn gamma inducing factor[tiab] or inducing factor, ifn-gamma[tiab] or il18[tiab] or interleukin-2[tiab] or interleukin 2[tiab] or il-2[tiab] or il2[tiab] or tcgf[tiab] or interleukine 2[tiab] or lymphocyte mitogenic factor[tiab] or mitogenic factor, lymphocyte[tiab] or t-cell growth factor[tiab] or t cell growth factor[tiab] or t-cell stimulating factor[tiab] or t cell stimulating factor[tiab] or thymocyte stimulating factor[tiab] or interleukin ii[tiab] or ro-23-6019[tiab] or ro 23 6019[tiab] or ro236019[tiab] or ro-236019[tiab] or ro 236019[tiab] or ru 49637[tiab] or ru-49637[tiab] or ru49637[tiab] or interleukin-23[tiab] or interleukin 23[tiab] or il-23[tiab] or interleukin-27[tiab] or interleukin 27[tiab] or il-17d[tiab] or il27[tiab] or il-27[tiab] or interleukin-17d[tiab] or interleukin 17d[tiab] or interleukin-3[tiab] or interleukin 3[tiab] or il-3[tiab] or mast-cell colonystimulating factor[tiab] or multipotential colony-stimulating factor[tiab] or multipotential colony stimulating factor[tiab] or erythrocyte burst-promoting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e51 appendix 1: medline search query search terms factor[tiab] or erythrocyte burst promoting factor[tiab] or burst-promoting factor, erythrocyte[tiab] or burst promoting factor, erythrocyte[tiab] or colony-stimulating factor 2 alpha[tiab] or colony-stimulating factor, mast-cell[tiab] or colony stimulating factor, mast cell[tiab] or colony-stimulating factor, multipotential[tiab] or colony stimulating factor, multipotential[tiab] or eosinophil-mast cell growth-factor[tiab] or eosinophil mast cell growth factor[tiab] or hematopoietin-2[tiab] or hematopoietin 2[tiab] or p-cell stimulating factor[tiab] or p cell stimulating factor[tiab] or interleukin-33[tiab] or interleukin 33[tiab] or il33[tiab] or il-33[tiab] or interleukin-4[tiab] or interleukin 4[tiab] or b-cell growth factor-1[tiab] or b cell growth factor 1[tiab] or b-cell growth factor-i[tiab] or b cell growth factor i[tiab] or b-cell proliferating factor[tiab] or b cell proliferating factor[tiab] or b-cell stimulating factor-1[tiab] or b cell stimulating factor 1[tiab] or b-cell stimulatory factor 1[tiab] or b-cell stimulatory factor-1[tiab] or bcgf-1[tiab] or binetrakin[tiab] or bsf-1[tiab] or il-4[tiab] or il4[tiab] or mast cell growth factor-2[tiab] or mast cell growth factor 2[tiab] or mcgf-2[tiab] or b cell stimulatory factor-1[tiab] or b cell stimulatory factor 1[tiab] or interleukin-5[tiab] or interleukin 5[tiab] or bcgf-ii[tiab] or differentiation factor, eosinophil[tiab] or t-cellreplacing factor[tiab] or t cell replacing factor[tiab] or il-5[tiab] or il5[tiab] or t-cell replacing factor[tiab] or replacing factor, t-cell[tiab] or b-cell growth factor-ii[tiab] or b cell growth factor ii[tiab] or eosinophil differentiation factor[tiab] or interleukin-6[tiab] or interleukin 6[tiab] or il6[tiab] or b-cell stimulatory factor 2[tiab] or b-cell stimulatory factor-2[tiab] or differentiation factor-2, b-cell[tiab] or differentiation factor 2, b cell[tiab] or b-cell differentiation factor-2[tiab] or b cell differentiation factor 2[tiab] or bsf-2[tiab] or hybridoma growth factor[tiab] or growth factor, hybridoma[tiab] or ifn-beta 2[tiab] or plasmacytoma growth factor[tiab] or growth factor, plasmacytoma[tiab] or hepatocyte-stimulating factor[tiab] or hepatocyte stimulating factor[tiab] or mgi-2[tiab] or myeloid differentiation-inducing protein[tiab] or differentiation-inducing protein, myeloid[tiab] or myeloid differentiation inducing protein[tiab] or b-cell differentiation factor[tiab] or b cell differentiation factor[tiab] or differentiation factor, b-cell[tiab] or differentiation factor, b cell[tiab] or il-6[tiab] or interferon beta-2[tiab] or interferon beta 2[tiab] or beta-2, interferon[tiab] or b cell stimulatory factor-2[tiab] or b cell stimulatory factor 2[tiab] or interleukin-7[tiab] or interleukin 7[tiab] or il7[tiab] or lymphopoietin-1[tiab] or lymphopoietin 1[tiab] or il-7[tiab] or interleukin-8[tiab] or interleukin 8[tiab] or il8[tiab] or monocyte-derived neutrophil chemotactic factor[tiab] or neutrophil activation factor[tiab] or neutrophilactivating peptide, lymphocyte-derived[tiab] or lymphocyte-derived neutrophil-activating peptide[tiab] or neutrophil activating peptide, lymphocyte derived[tiab] or neutrophil-activating peptide, monocyte-derived[tiab] or monocyte-derived neutrophil-activating peptide[tiab] or neutrophil activating peptide, monocyte derived[tiab] or alveolar macrophage chemotactic factor-i[tiab] or alveolar macrophage chemotactic factor i[tiab] or amcf-i[tiab] or anionic neutrophil-activating peptide[tiab] or anionic neutrophil activating peptide[tiab] or neutrophil-activating peptide, anionic[tiab] or peptide, anionic neutrophil-activating[tiab] or chemokine cxcl8[tiab] or cxcl8, chemokine[tiab] or chemokines, cxcl8[tiab] or cxcl8 chemokines[tiab] or chemotactic factor, macrophage-derived[tiab] or chemotactic factor, macrophage derived[tiab] or macrophage-derived chemotactic factor[tiab] or chemotactic factor, neutrophil[tiab] or neutrophil chemotactic factor[tiab] or chemotactic factor, neutrophil, monocyte-derived[tiab] or cxcl8 chemokine[tiab] or chemokine, cxcl8[tiab] or granulocyte chemotactic peptide-interleukin-8[tiab] or chemotactic peptide-interleukin-8, granulocyte[tiab] or granulocyte chemotactic peptide interleukin 8[tiab] or il-8[tiab] or interleukin-9[tiab] or interleukin 9[tiab] or t-cell growth factor p40[tiab] or t cell growth factor p40[tiab] or p40 t-cell growth factor[tiab] or p40 t cell growth factor[tiab] or il-9[tiab] or il9[tiab] 4. #1 and #2 and #3 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e70 or i g i n a l re s e a rc h cardiopulmonary resuscitation outcomes of patients with covid-19; a one-year survey afshin goodarzi1, masoud khodaveisi2, alireza abdi3, rasoul salimi4, khodayar oshvandi5∗ 1. department of nursing, hamadan university of medical sciences, hamadan, iran. 2. chronic diseases (home care) research center, department of community health nursing, hamadan university of medical sciences, hamadan, iran. 3. department of nursing, school of nursing & midwifery, kermanshah university of medical sciences, kermanshah, iran. 4. department of emergency medicine, school of medicine, besat hospital, hamadan university of medical sciences, hamadan, iran. 5. mother and child care research center, nursing and midwifery school, hamadan university of medical sciences, hamadan, iran. received: august 2021; accepted: september 2021; published online: 4 november 2021 abstract: introduction: assessing cardiopulmonary resuscitation (cpr) outcomes of patients with covid-19 and employing effective strategies for their improvement are essential. this study is designed in this regard. methods: this cross-sectional study was conducted between january 20, 2020 and january 20, 2021 in the emergency departments of two hospitals in hamadan and kermanshah, iran. participants were 487 patients with confirmed covid-19 and cardiac arrest (ca) who had undergone cpr during the study period. data were collected using the available cpr documentation forms developed based on the utstein style and analyses were performed using chi-square, fisher’s exact, and mann-whitney u tests and the logistic regression analysis. results: participants’ mean age was 69.31±14.73 years and most of them were male (61.8%) and suffered from at least one underlying disease (58.1%). the rate of total and in-hospital ca was 9.67% and 9.39%, respectively. the most prevalent first documented rhythm was asystole (67.9%) and the highest responsivity to cpr was for shockable rhythms. the rate of the return of spontaneous circulation (rosc) was 9% and the rate of survival to hospital discharge was 2%. the significant predictors of cpr success were age (p = 0.035), epinephrine administration time interval (p = 0.00), cpr duration (p = 0.00), and first documented rhythm (p = 0.009). conclusion: the rate of in-hospital ca among studied covid-19 cases was 9.39% with 9% rosc and 2% survival to hospital discharge rates after cpr. primary cpr success among patients with covid-19 was poor, particularly among those with asystole and bradycardia. it seems that old age and improper doses of epinephrine can reduce cpr success. keywords: cardiopulmonary resuscitation; heart arrest; covid-19; epinephrine cite this article as: goodarzi a, khodaveisi m, abdi a, salimi r, oshvandi k. cardiopulmonary resuscitation outcomes of patients with covid-19; a one-year survey. arch acad emerg med. 2021; 9(1): e70. https://doi.org/10.22037/aaem.v9i1.1381. 1. introduction involvement of the cardiovascular system, particularly among patients with a history of cardiovascular disease, is one of the most serious complications of covid-19 (1). although covid-19 is primarily manifested as a severe respiratory infection, different studies reported that it can cause stroke due to cerebrovascular ischemia, pulmonary ∗corresponding author: khodayar oshvandi; mother and child care research center, nursing and midwifery school, hamadan university of medical sciences, hamadan, iran. email: oshvandi2005@gmail.com, mobile number: +989188117729, orcid: http://orcid.org/0000-0002-2224-8870. artery thrombosis, spontaneous pneumothorax, cardiovascular disease, and type ii diabetes mellitus due to the dysfunction of the pancreatic beta cells (2-6). respiratory dysfunction and subsequent alteration of tissue oxygenation in patients with covid-19 can directly affect the cardiovascular system and cause serious problems such as myocarditis, myocardial injuries, acute myocardial infarction, heart failure, cardiac dysrhythmia, and thromboembolism. these problems can lead to cardiac arrest (ca) (7). studies on patients with covid-19 show the increasing prevalence of in-hospital and out-of-hospital ca. for example, a study reported two times increase in the rate of out-ofhospital ca and reduced survival during the covid-19 pandemic (8). a meta-analysis on four studies also indicated two this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. goodarzi et al. 2 times increase in the rate of in-hospital ca among patients with covid-19 (9). before the covid-19 pandemic, in the u.s., an average of 292,000 cardiac arrests occurred annually (10, 11). there are no reliable statistics on ca rate in iran; however, the average rates of ca in the united arab emirates and saudi arabia were respectively 11.7 and 7.76 cases per 1000 hospitalizations before the pandemic (12, 13). the american heart association noted that cpr for patients with covid-19 is the same as cpr for patients without covid-19 but recommended the use of personal protective equipment throughout cpr in order to reduce the risk of infection transmission (14). for instance, a study in china reported that the primary cpr outcomes among patients with covid-19 are poor success rate and thirty-day survival rate were 13.2% and 2.9%, respectively(15). two other studies on out-of-hospital and in-hospital ca among patients with covid-19 reported a survival to hospital discharge rate of zero percent (16, 17). cpr outcomes depend on a wide range of factors such as cause of ca, underlying disease, the first documented rhythm, age, ca type (witnessed or unwitnessed), cpr duration, response time, call-to-arrival time, and adherence to cpr protocols (18-21). the lower cpr success rate among patients with covid-19 has been attributed to factors such as the first documented rhythm (15, 16, 22). despite the wide prevalence and the high mortality rate of covid-19 throughout the world, there are limited reliable data about cpr and its outcomes among afflicted patients. this study aimed to assess the epidemiology and one-year outcomes of cpr among patients with covid-19. ‡ ‡ 2. methods 2.1. study design and setting this cross-sectional study was conducted on cprs performed for patients with confirmed covid-19 during the one-year period between january 20, 2020 and january 20, 2021 in emergency departments of besat hospital, hamadan, iran, and imam reza hospital complex, kermanshah, iran. the institutional review board and the ethics committee of hamadan university of medical sciences, hamadan, iran, approved the study protocol (codes: 9909186284 and ir.umsha.rec.1399.689). necessary permissions for entering the study setting and performing data collection were obtained from the research administration of hamadan and kermanshah universities of medical sciences, hamadan and kermanshah, iran, and provided to the authorities of the study setting. patients’ data were managed confidentially. it is noteworthy that in the study setting, consents for using patient data for research purposes were routinely obtained from patients and their family members at the time of hospital admission and were available via in-patient medical records. 2.2. participants study population consisted of all patients with confirmed covid-19, who had been hospitalized in the two mentioned hospitals and had undergone out-of-hospital or in-hospital cpr. inclusion criteria were age over eighteen years, definite diagnosis of covid-19 (based on pcr or pcr and high resolution computed tomography (hrct), depending on the hemodynamic status), and out-of-hospital or in-hospital ca based on the utstein style criteria (23, 24). patients with ca and no indication of cpr (i.e., those with rigor mortis or livor mortis) were not included. patients with out-of-hospital ca and return of spontaneous circulation (rosc) before hospital arrival who experienced another ca in emergency department were considered as out-of-hospital ca. 2.3. data collection the data collection instrument was the standard national cpr forms, which had been developed based on the utstein style and were routinely used for cpr documentation by cpr nurses in the study setting. the items on these forms include demographic characteristics, underlying disease, initial and final diagnoses, consciousness on arrival, ca type (in-hospital or out-of-hospital), out-of or in-hospital cpr, the first documented cardiac rhythms, use of defibrillation, necessary time for intravenous (iv ) cannulation, administered medications during cpr, cpr duration, and cpr success. data were collected from patients’ medical records. hospital discharge status (dead or alive) was also assessed using the electronic medical record system of the study setting. based on the utstein style, the core cpr success outcomes are rosc, post-cpr survival up to hospital discharge or for thirty days, and optimum neurological function up to hospital discharge or for thirty days. complementary outcome based on this style is one-year survival after successful cpr (23). in this study, rosc was considered as the primary outcome of cpr and post-cpr survival to hospital discharge was considered as the final outcome of cpr. we defined adrenaline average dosing interval as the time between the first adrenaline dose and the resuscitation endpoint, divided by the total number of adrenaline doses received after the first dose. 2.4. data analysis data were analyzed using spss software (v. 20.0). the normality of age and cpr duration variables was tested using kolmogorov-smirnov test. chi-square, fisher’s exact, and mann-whitney u tests were used to assess the relationship of cpr outcomes with demographic characteristics, cpr time, cpr duration, epinephrine administration intervals, and iv this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e70 table 1: baseline characteristics and outcomes of cardiopulmonary resuscitation in studied cases variable n (%) rosc survival* gender male 301 (61.8) 31(10.30) 7 (2.32) female 186 (38.2) 13 (6.99) 3 (1.61) type of ca in-hospital 471 (96.7) 43 (9.13) 10 (2.12) out-of-hospital 16 (3.3) 1 (6.25) 0 (0) on-arrival status alert 242 (51.2) 25(10.33) 6 (2.48) verbal 131 (27.6) 16(12.21) 4 (3.05) painful 51 (10.8) 2 (3.92) 0 (0) unresponsive 50 (10.5) 1 (2.0) 0 (0) cpr time 08:00–14:00 131 (26.9) 15(11.45) 2 (1.53) 14:01–20:00 126 (25.9) 12 (9.52) 5 (3.97) 20:01–24:00 80 (16.4) 6 (7.5) 0 (0) 00:01–07:59 150 (30.8) 11 (7.33) 3 (2) underlying disease hypertension 95(26.4) 11(11.58) 2(2.10) diabetes mellitus 95(26.4) 10(10.53) 1(1.05) cancer 34(9.4) 3(8.82) 0(0) ihd 70(19.4) 7(10) 3(4.29) ckd 15(4.2) 1(6.66) 1(6.66) copd 10(2.8) 0(0) 0(0) transplantation 2(0.5) 0(0) 0(0) cva 6(1.7) 0(0) 0(0) other 33(9.2) 1(3.03) 0(0) first documented rhythm ventricular tachycardia 3 (0.6) 2 (66.66) 1 (33.33) ventricular fibrillation 3 (0.6) 1 (33.33) 0 (0) asystole 330 (67.9) 31 (9.39) 4 (1.21) pea 3 (0.6) 0 (0) 0 (0) bradycardia 147 (30.2) 10 (7.30) 5 (3.40) epinephrine administration intervals < 3 minutes 2 (0.4) 0 (0) 0 (0) 3–5 minutes 66 (13.7) 23(34.85) 6 (9.09) > 5 minutes 414 (85.9) 21 (5.07) 4 (0.97) intravenous cannulation time < 1 minutes 464 (95.3) 43 (9.27) 10 (2.15) >1 minute 23 (4.7) 1 (4.35) 0 (0) epinephrine delay yes 38(7.9) 2(5.26) 0(0) no 446(92.1) 42(9.42) 10(2.24) atropine yes 128(87.7) 9(7.03) 4(3.12) no 19(12.93) 1(5.26) 1(5.26) amiodarone yes 5(83.33) 3(60) 1(20) no 1(16.67) 0(0) 0(0) defibrillation yes 6(100) 3(50) 1(33.33) no 0(0) (0) 0(0) airway management intubation 479(98.56) 43(8.98) 10(2.09) mask 7(1.44) 1(14.28) 0(0) data are presented as number (%). ca: cardiac arrest; cpr: cardiopulmonary resuscitation; copd: chronic obstructive pulmonary disease; cva: cerebrovascular accident; ckd: chronic kidney disease; ihd: ischemic heart disease; pea: pulseless electrical activity. * survival to discharge. cannulation time. moreover, logistic regression analysis was performed to predict cpr outcomes. variables with a significant relationship with cpr outcomes in univariable analysis were entered into the logistic regression model. 3. results 3.1. baseline characteristics of studied cases during the one-year assessment period of the study, 5034 patients with covid-19 had been hospitalized in the studied hospitals and 487 of them had experienced out-of-hospital or in-hospital ca. the mean age of patients with ca was 69.31±14.73 years and most of them were male (61.8%) and suffered from at least one underlying disease (58.1%). basethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. goodarzi et al. 4 table 2: the relationships of participants’ characteristics with return of spontaneous circulation (rosc) variable rosc p-value gender male 31 (10.30) 0.216 female 13 (6.99) type of ca in-hospital 43 (9.13) 0.693 out-of-hospital 1 (6.25) on-arrival status alert 25 (10.33) 0.088 verbal 16 (12.21) painful 2 (3.92) unresponsive 1 (2.0) cpr time 08:00–14:00 15 (11.45) 0.632 14:01–20:00 12 (9.52) 20:01–24:00 6 (7.5) 00:01–07:59 11 (7.33) underlying disease yes 21 (7.72) 0.142 no 23 (11.73) first documented rhythm ventricular tachycardia 2 (66.66) 0.023* ventricular fibrillation 1 (33.33) asystole 31 (9.39 pea 0 (0) bradycardia 10 (7.30) epinephrine administration intervals < 3 minutes 0 (0) < 0.001* 3–5 minutes 23 (34.85) > 5 minutes 21 (5.07) intravenous cannulation time < 1 minutes 43 (9.27) 0.422 >1 minutes 1 (4.35) epinephrine delay yes 2(5.26) 0.393 no 42(9.42) atropine yes 9(7.03) 0.775 no 1(5.26) amiodarone yes 3(60) 1.00 no 0(0) defibrillation yes 3(50) n/a‡ no (0) airway management intubation 43(8.98) 0.488 mask 1(14.28) data are presented as number (%).ca: cardiac arrest; cpr: cardiopulmonary resuscitation; pea: pulseless electrical activity. ‡ not available. * significant at level 0.05. line characteristics and cpr outcomes of the studied cases are presented in table 1. the total rate of ca among patients with covid-19 was 9.67% and the total rate of in-hospital ca was 9.39%. among patients with out-of-hospital ca, only 12.5% had been taken to hospital by the emergency medical services and had received cpr before hospital arrival. the most prevalent cardiac dysrhythmia was asystole (67.9%) and the mean cpr duration was 41.98 ± 8.98 minutes. the time interval between each two epinephrine administrations was 9.02 ± 4.31 minutes and in most cases (95.3 %) iv cannulation had been performed in less than one minute. the mean age of patients who experienced rosc was 64.82±14.00 years, which was significantly less than the mean age in patients who had not experienced rosc (69.76±14.74 years; z=-2.464; p = 0.014). the mean age of patients who experienced survival to discharge was 64.50±9.11 years, and less than the mean age in patients who did not survive until discharge (64.91±15.26; z=-0.533; p = 0.594). also, the mean cpr duration of patients who experienced rosc was 24.09±12.58 minutes, which was significantly shorter than the mean cpr duration in patients who had not experienced rosc (43.77±6.17 minutes; z=9.716; p = 0.00), and the mean cpr duration of patients who experienced survival to discharge was 18.80±5.83 minutes, this time was 25.65±13.64 minutes in patients who did not survive to discharge (z=-1.101; p = 0.271). the total rates of rosc and survival to hospital discharge were 9.03% and 2.05%, respectively (table 1). 3.2. outcomes the rosc outcome significantly correlated with participants’ age (p = 0.014), the first documented rhythm (p = this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e70 table 3: the relationships of participants’ characteristics with survival to discharge variable survival† p-value gender male 7 (2.32) 0.971 female 3 (1.61) type of ca in-hospital 10 (2.12) 1.00 out-of-hospital 0 (0) on-arrival status alert 6 (2.48) 1.00 verbal 4 (3.05) painful 0 (0) unresponsive 0 (0) cpr time 08:00–14:00 2 (1.53) 0.194 14:01–20:00 5 (3.97) 20:01–24:00 0 (0) 00:01–07:59 3 (2) underlying disease yes 5 (1.84) 0.870 no 5 (2.55) first documented rhythm ventricular tachycardia 1 (33.33) 0.042* ventricular fibrillation 0 (0) asystole 4 (1.21) pea 0 (0) bradycardia 5 (3.40) epinephrine administration intervals < 3 minutes 0 (0) 0.578 3–5 minutes 6 (9.09) > 5 minutes 4 (0.97) intravenous cannulation time < 1 minutes 10 (2.15) 1.00 >1 minutes 0 (0) epinephrine delay yes 0 (0) 1.00 no 10(2.24) atropine yes 4(3.12) 1.00 no 1(5.26) amiodarone yes 1(20) n/a‡ no 0(0) defibrillation yes 1(33.33) n/a‡ no 0(0) air way management intubation 10(2.09) 1.00 mask 0(0) data are presented as number (%). ca: cardiac arrest; cpr: cardiopulmonary resuscitation. † survival to discharge. ‡ not available. * significant at level 0.05. table 4: the predictors of cardiopulmonary resuscitation (cpr) outcomes dependent independent b se wald df p-value or 95% ci lower upper rosc first documented rhythm (vt) 3.311 1.268 6.819 1 0.009* 27.40† 2.284 328.774 epinephrine interval (q/3–5min) 2.304 0.342 45.394 1 < 0.001* 10.010‡ 5.122 19.564 cpr duration -0.198 0.022 82.010 1 < 0.001* 0.820 0.785 0.856 age -0.021 0.010 4.442 1 0.035* 0.979 0.960 0.999 survival to discharge first documented rhythm (asystole) -1.910 1.512 1.594 1 0.207 0.148¶ 0.008 2.871 †. reference level: bradycardia;‡. reference level: epinephrine administration intervals> 5 minutes; ¶. reference level: vt; * significant at level 0.05. se: standard error; or: odds ratio. rosc: return of spontaneous circulation; ci: confidence interval; vt: ventricular tachycardia. 0.023), epinephrine administration time interval (p= 0.001), and cpr duration (p = 0.001) but survival to hospital disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. goodarzi et al. 6 charge only had a significant relationship with the first documented rhythm (p = 0.042; tables 2 and 3, respectively). the results of the regression analysis showed age (p = 0.035), epinephrine administration time interval (p = 0.001), the first documented rhythm (p = 0.009), and cpr duration (p = 0.001) as the significant predictors of rosc (table 4). 4. discussion the rate of in-hospital ca among studied covid-19 cases was 9.39% with 9% rosc and 2% survival to hospital discharge rates after cpr. primary cpr success among patients with covid-19 was poor, particularly among those with asystole and bradycardia. it seems that old age and high or low doses of epinephrine can reduce cpr success. in line with this finding, a previous study reported that the rate of in-hospital ca among patients with covid-19 was 10% (9). most participants suffered from at least one underlying disease, particularly diabetes mellitus, hypertension, cardiovascular disease, and cancer. a meta-analysis also reported the prevalence of different underlying diseases among patients with covid-19 (25). affliction by underlying diseases increases mortality rate among patients with covid-19 (25, 26). compromised immunity due to diabetes mellitus, decreased inflammatory cytokines among patients with cardiovascular disease, or chemotherapy among patients with cancer is considered as a major risk factor for affliction by covid-19 (27, 28). on the other hand, findings showed that 41.9% of participants had no underlying disease, denoting the high prevalence of covid-19 among people with no underlying disease. these findings question the widespread belief that covid-19 affects people with no underlying disease less frequently. the high transmissibility of the virus is a significant factor contributing to the high prevalence of covid-19 even among people with no underlying disease. primary cpr success, i.e., rosc, was observed among only 9% of the patients with covid-19 who had experienced ca. cpr success rate among patients with in-hospital cpr was also higher than patients with out-of-hospital cpr. a previous study in this area reported that the rate of rosc after cpr was 25.9% for out-of-hospital ca and 30.6% for in-hospital ca (16). moreover, a meta-analysis on four studies on 621 patients with covid-19 showed that the pooled prevalence of primary cpr success was 39% (95% ci: 21.0%–59.0%) (9). the rate of primary cpr success in the two mentioned studies are much better than the rate in our study. comparison of the findings of the present study with the findings of two previous studies in iran before the covid-19 pandemic also reveals a lower cpr success rate among patients with covid-19 (21, 29). this lower cpr success rate can be attributed to the higher prevalence of asystole in the present study compared with previous studies on patients with and without covid-19 (16, 17, 29, 30). asystole is less responsive to cpr than other shockable dysrhythmias. another reason for the lower cpr success rate in the present study may be non-adherence to epinephrine administration protocols. some studies also reported that poor cpr outcomes among patients with covid-19 may be due to the employment of novice staff for cpr during the covid-19 pandemic, delayed cpr onset due to the need for using personal protective equipment, and cpr staff’s concern over affliction by covid-19 during cpr (31, 32). delayed or slow cpr onset and subsequent cpr prolongation have significant negative relationships with cpr outcomes (33-35). the lower rate of cpr success among patients with out-of-hospital ca in the present study may also be due to the fact that only 12.5% of them had been taken to hospital by emergency medical services and the others had been transported using private vehicles or taxi and hence, had not received out-of-hospital cpr. a previous study had also reported the same finding (36). study findings showed that only 2% of patients had survival to hospital discharge. all these patients had experienced inhospital ca. a meta-analysis on patients with covid-19 and in-hospital ca also reported that the cumulative prevalence of survival to discharge rate was 3% (9), while in two other studies none of the patients with covid-19 and in-hospital ca had survived to hospital discharge (16, 30). covid-19 significantly affects different body organs and hence, ca among afflicted patients is mostly fatal. therefore, preventive measures, timely treatments, and careful monitoring of criticallyill patients with covid-19 are necessary to prevent the occurrence of ca. findings revealed that primary cpr success a had significant relationship with age, the first documented rhythm, epinephrine administration interval, and cpr duration, while final cpr success had a significant relationship only with the first documented rhythm. the logistic regression analysis revealed age, epinephrine administration interval, the first documented rhythm, and cpr duration as the significant predictors of primary cpr success. the mean cpr duration was 24 minutes (with an interquartile range of 15–30) for patients with successful primary cpr and 43 minutes for unsuccessful cpr. the mean cpr duration was six minutes (with an interquartile range of 4–14) among patients with successful primary cpr and in-hospital ca in a previous study (22) and eight minutes (with an interquartile range of 4–10) in another study (17). the longer cpr duration in the present study compared with previous studies may be due to the fact that the study included patients with out-of-hospital ca. a study reported that there is no maximum time for cpr efforts, while longer cprs were associated with greater survival to discharge rate (37). although the mean cpr duration among survived patients in the present study was shorter, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e70 6.8% of successful cprs had lasted more than 45 minutes, denoting that cpr prolongation can be a determining factor in cpr success. the mean of participants’ age in the present study was 69 years and the mean age among participants with successful cpr was significantly less than those with unsuccessful cpr. the results of a meta-analysis on more than half a million patients with covid-19 from different countries also reported age as a significant predictor of mortality (38). these findings highlight the importance of timely preventive measures for older patients to improve treatment outcomes among them because they are less responsive to treatments in critical conditions such as ca. epinephrine administration interval was one of the significant predictors of primary cpr success in the present study. this interval was 5.41±1.74 minutes for patients with successful primary cpr. the rates of primary cpr success and survival to hospital discharge were 34.85% and 9.09%, respectively, for patients who had received epinephrine every 3–5 minutes, and 5.07% and 0.97% for patients who had received it in intervals longer than five minutes. moreover, none of the patients who had received extra high doses of epinephrine (i.e., with intervals less than three minutes) had experienced successful primary cpr and survived to hospital discharge. the standard dose of epinephrine for adults is 1 milligram every 3–5 minutes throughout cpr (39). our findings showed that cpr success among patients who had received high doses of epinephrine was less than those who had received it in doses less than the recommended standard dose. although poor cpr outcomes among patients with covid-19 can be attributed to covid19 severity, the role of high doses of epinephrine in causing cytokine storms should be taken into account. further studies are needed to assess this role and the necessity to use safer medications instead of epinephrine for the cpr of patients with covid-19. the most prevalent first documented cardiac rhythms among study participants were asystole and bradycardia, respectively, and the prevalence of shockable dysrhythmias was 1.24%. the prevalence of shockable dysrhythmias in five earlier studies on patients with covid-19 was 3.7%–13%, which is less than the rate among patients without covid19 (15-17, 22, 30). pulmonary involvement and its associated hypoxia may be a reason for the lower rate of shockable dysrhythmias among patients with covid-19. the highest rate of successful primary cpr and survival to discharge rate were among patients with pulseless ventricular tachycardia. the first documented rhythm was a significant predictor of primary cpr success in the present study. studies on patients without covid-19 (40, 41) and a meta-analysis on patients with covid-19 found poorer cpr outcomes for patients with non-shockable dysrhythmias (9). despite the lower prevalence of shockable dysrhythmias among patients with covid-19, these dysrhythmias have better prognosis than non-shockable dysrhythmias. although the primary cpr success rate in our study was lower than the results reported by other studies in this area, the survival to hospital discharge rate in this study was at an acceptable level compared to other studies. the prevalence of shockable dysrhythmias among patients with covid-19 is also much lower than patients without covid-19, resulting in lower responsiveness to cpr among patients with covid19. old age and high doses of epinephrine are factors that can negatively affect cpr outcomes, particularly primary cpr success, among patients with covid-19. further studies are needed to assess the effects of epinephrine administration on cpr outcomes among these patients. although the mean cpr duration among survived patients in the present study was shorter, the increase in resuscitation time was associated with an increase in the number of survivors. on the other hand, by comparing the results of the present study with studies conducted in iran before the epidemic, and in non-covid patients, it can be claimed that the outcomes of resuscitation are weaker in patients with covid-19. poor cpr outcomes among patients with covid-19 highlight the importance of exploring cpr staff’s experiences and the effects of their concerns over affliction by covid-19 on cpr quality and outcomes. 5. limitations our study had limitations; in some cases, some information related to the resuscitation process was not available in resuscitation registration forms and patient records. it is possible for some information to be incorrectly recorded by cpr staff, and these limitations were beyond the control of the researchers. 6. conclusion the rate of in-hospital ca among studied covid-19 cases was 9.39% with 9% rosc and 2% survival to hospital discharge rates after cpr. primary cpr success among patients with covid-19 was poor, particularly among those with asystole and bradycardia. it seems that old age and high or low doses of epinephrine can reduce cpr success. 7. list of abbreviations cpr: cardio pulmonary resuscitation, ca: cardiopulmonary arrest, iv: intravenous, rosc: return of spontaneous circulation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. goodarzi et al. 8 8. declarations 8.1. availability of data the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. 8.2. acknowledgments we would like to thank the research administration of hamadan university of medical sciences, hamadan, iran, as well as the authorities, nurses, and medical records staff of the study setting who helped us conduct this study. 8.3. funding financial resources for the design of the present study and collection, analysis, and interpretation of data and writing the manuscript are provided by hamadan university of medical sciences. 8.4. competing interests the authors declare that they have no competing interests. 8.5. conflict of interest statement the authors declare that they have no competing interests 8.6. author contribution study design: ag, ko; data gathering: ag, rs; analysis: ag, ara; interpreting: ag, , mk, ara; drafting: ag, ko; critically revised the paper: all authors. 8.7. data presentation the information of this manuscript has not been presented in any meeting(s). references 1. ranard ls, fried ja, abdalla m, anstey de, givens rc, kumaraiah d, et al. approach to acute cardiovascular complications in covid-19 infection. circulation: heart failure. 2020;13(7):e007220. 2. y galán jtg. stroke as a complication and prognostic factor 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drennan ir, hirsch kg, et al. part 3: adult basic and advanced life support: 2020 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2020;142(16_suppl_2):s366-s468. 40. nolan jp, soar j, smith gb, gwinnutt c, parrott f, power s, et al. incidence and outcome of in-hospital cardiac arrest in the united kingdom national cardiac arrest audit. resuscitation. 2014;85(8):987-92. 41. nadkarni vm, larkin gl, peberdy ma, carey sm, kaye w, mancini me, et al. first documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults. jama. 2006;295(1):50-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion list of abbreviations declarations references archives of academic emergency medicine. 2022; 10(1): e35 or i g i n a l re s e a rc h challenges of emergency medical services response to arasbaran twin earthquakes; a content analysis mahboub pouraghaei1, javad babaie2,3∗, laleh rad saeed4 1. department of emergency medicine, faculty of medicine, tabriz university of medical sciences, tabriz, iran. 2. department of health policy and management, school of management and medical informatics, tabriz university of medical sciences, tabriz, iran. 3. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. 4. faculty of medicine, tabriz university of medical sciences, tabriz, iran. received: january 2021; accepted: march 2021; published online: 1 may 2022 abstract: introduction: one of the most important concerns in responding to disasters is providing basic life support (bls) services. considering the key role of emergency medical services (ems) in providing bls, the purpose of this study is to investigate the experience of provincial ems during their response to the arasbaran twin earthquakes and its challenges in iran. methods: this study was conducted using a qualitative approach and the conventional content analysis method. data were collected through focused group discussions (fgd) and semi-structured in-depth interviews with purposively-selected ems paramedics and officials in east azerbaijan province, iran. to form the main categories, the interviews were encoded in three stages and the similar codes were placed under the same subcategories and merged. results: a total of 26 ems paramedics participated in the study. the codes extracted from the interviews, after three stages of reduction, were placed in the top ten categories, including the lack of preparedness and coordination, dead bodies’ management challenges, responders’ psychosocial support, deficiencies in supplies and ambulances, difficulty of access to rural areas, volunteer management, non-documentation of the experiences, communication challenges, recalling, and deploying of ems responders. conclusion: timely response of the ems and paramedics’ sense of responsibility for providing services were positive and successful points about the emergency response operations. the weaknesses of ems should, therefore, be addressed through transferring of experiences and by planning and arranging training courses. keywords: emergency medical services; earthquakes; disasters; emergencies cite this article as: pouraghaei m, babaie j, rad saeed l. challenges of emergency medical services response to arasbaran twin earthquakes; a content analysis. arch acad emerg med. 2022; 10(1): e35. https://doi.org/10.22037/aaem.v10i1.1571. 1. introduction disasters are destructive phenomena imposed on human life (1-3). every year, hundreds of disasters occur around the world. in 2017, for example, 318 disasters occurred throughout the world, with 9503 deaths, more than 96 million affected, and more than $314 billion in financial damages (4). iran is one of the most disaster-prone countries. more than 90% of the country and almost all its mega cities are at risk ∗corresponding author: javad babaie; department of health policy and management, iranian center of excellence in health management, school of management and medical informatics, tabriz university of medical sciences, tabriz, iran. email: javad1403@yahoo.com, fax: +98 4152622456, tel: +98 9144236905, orcid: https://orcid.org/0000-0001-6155-5606. of floods and earthquakes (5). on average, in iran, more than 4000 die each year due to natural disasters and more than 55,000 are affected (6). disasters, particularly those who release a lot of energy, damage the structures and injure the people living in them. rescuing these casualties from the rubble and providing immediate medical care can reduce the number of deaths and complications (7). medical services are the most important requirement of the affected people during the first moments after disasters. therefore, ems is one of the key components of every disaster response (7). ems is the main provider of basic life support (bls) in the early moments after a disaster (8). since the launch of these systems around the world, they have become a leading organization in response to disasters (8). the preparedness of these systems, and their timely effective response has sigthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 2 table 1: the demographic characteristics of the study participants variable number (%) education general physician 5 (19.23) masters degree 4 (15.38) bachelors degree 11 (42.31) associate degree 6 (23.08) work experience more than 25 years 4 (15.38) 20-24 years 6 (23.08) 15-19 years 5 (19.23) 10-14 years 4 (15.38) 5-9 years 3 (11.54) less than 5 years 4 (15.38) workplace emergency department 11 (42.31) city ems headquarters 5 (19.23) ems headquarters of the province 10 (38.48) ems: emergency medical service nificantly reduced the number of deaths and adverse effects caused by disasters (9). absence of triage on the disaster scene, lack of basic lifesupporting services, and unplanned transportation of injured people to other cities were the main limitations of ems in bam earthquake (7). according to sorani et al., iranian ems is faced with six main categories of challenges in response to disasters; namely: people-related problems, infrastructural shortcomings, mismanagement of information, management obstacles, insufficient number of paramedics and presence of concerns regarding their safety/security, and challenges of medical services (10). findings of khankeh et al. reveals that unplanned response, chaotic service providing, duty overlaps, and lack of coordination between different service providers were the main challenges of iranian health system in response to bam earthquake (5). on august 21, 2012, two earthquakes, with a magnitude of 6.2 and 6.3 on the richter scale, shook haris, varzaghan and ahar (arasbaran) districts in east azerbaijan province and injured more than 3000 (11). the provincial pre-hospital emergency department was involved in response to the earthquakes. after the disruptive earthquake in bam, it was the first experience of iranian ems in response to such a major disaster. it was so important for us to examine this experience and explore their challenges. disaster management specialists believe that such investigations can improve/help resolve the current challenges of health systems in facing with disasters (7). the aim of this study is, therefore, to investigate the experiences of ems in response to arasbran twin earthquakes. 2. method 2.1. study design and setting purposively selected ems paramedics and officials who were directly involved in responding to arasbaran (ahar, haris and varzaghan) twin earthquakes in 2012 (august-september) were the participants of this qualitative study. after receiving the approval of tabriz university of medical sciences (ethics code of study: ir.tbzmed.rec.1396.535), the researchers were referred to the central ems organization in tabriz. the selected participants were then interviewed or coordinated by focused group discussions (fgd) (2017 september) for data collection. the number of participants in each fgd was five to seven. the group discussions and interviews continued in ahar, haris, and varzaghan ems posts until data saturation was achieved. 2.2. participants the inclusion criteria for this study consisted of having been involved in response operations as an ems paramedic or official. the exclusion criteria were unwillingness to participate in the study and being unavailable. 2.3. data gathering the interviews and group discussions began with the interviewer presenting a summary of the project and its objectives to the interviewees. the interviews then continued with general questions, and based on participants’ responses, more in-depth questions were asked to extract rich interviewee experiences. all the responses were recorded by a recorder and immediately transcribed after the completion of the interview. a summary of all the discussions and participants’ behavior and body language during the sessions were recorded. all the statements made by the participants were then transcribed on paper with the exact same wording and were submitted to each participant to confirm or correct their statements. the text of the interviews and discussion was repeatedly studied to achieve immersion. 2.4. data analysis data analysis was carried out in the form of conventional content analysis, and started simultaneously in three stages (simultaneous analysis). at first, the initial codes were determined. the duplicate codes were then removed and the codes with the same concept were placed together to form the subcategories. the main categories were formed out of the merged subcategories. for meeting credibility, conformability, dependability, and transferability criteria, proposed by lincoln and cuba for qualitative researches, were considered. so, for increasing generalizability, transcriptions, meaning units, and extracted codes were sent to some of the participants. then we revised this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e35 the codes based on their comments. 3. results four fgds and five interviews were held with 26 participants. eighteen of them were ems paramedics and eight were officials. seven of the participants were women and 19 were men. all of them had either participated directly in providing services to the injured people in the early hours after the earthquakes or had been involved in managing the response. table 1 presents their profiles. after the earthquakes, ems started its response operation at two levels, including the district (local) and the provincial level. the paramedics who were present at the local ems posts in the earthquake-affected area had gone to the nearest villages from the very first moments after the turmoil along with other people and began to gather the injured in certain points, prioritize them and provide basic medical services for them; then, using ambulances, they began transferring the injured to district hospitals. at the local level, since the earthquake occurred in the afternoon and the buildings were closed and since the cities themselves were not severely damaged, the paramedics first ensured the family’s health and then deployed them locally (mostly to relatives’ homes) and immediately went to their departments and started the response operation. in the provincial department, almost all the officers had set up their families in a safe place after the earthquakes and had come back to their workplace within the first minutes. they had then begun getting information from earthquakeaffected districts. after getting the initial information, three rapid assessment teams were deployed to the affected areas. afterwards, the officers began calling on other coworkers from the provincial towns, and after about two hours, ambulances were deployed to the affected zones. since the earthquake-affected cities were in the neighboring of ardabil province, ambulances were immediately sent from this province to the city of ahar for relief. more ambulances were sent from west azerbaijan province. despite these efforts, most of the injured had reached the hospitals using their own personal cars, which were mostly unsuitable for carrying an injured. overall, more than 3000 earthquake victims were transferred to hospitals in the region. the initial response was almost completed around 2:00 am (approximately eight hours after the first shakes). after the analysis of the fgds and interviews and encoding them, the codes were finally extracted by eliminating the repetitive codes and merging the similar items. the similar codes (99 codes) were placed into subcategories, yielding 29 subcategories (table 2). the similar subcategories were also merged to form the top ten categories, including: 1lack of preparedness (14 codes; 3 main codes/categories) 2lack of coordination (18 codes; 4 main codes/categories) 3challenges of dead bodies’ management (4 codes; 2 main codes/categories) 4psychosocial support for the ems responders (11 codes; 5 main codes/categories) 5deficiencies and the lack of facilities, equipment, supplies and ambulances (13 codes; 3 main codes/categories) 6difficulty in access to damaged rural areas (7 codes; 3 main codes/categories) 7relief volunteers’ management (9 codes; 2 main codes/categories) 8lack of documentation of experiences (7 codes; 3 main codes/categories) 9the challenges of communicating with the earthquakeaffected areas and between teams (7 codes; 2 main codes/categories) 10recalling and deploying ems responders (9 codes; 2 main codes/categories) 1lack of preparedness the lack of preparedness among the ems paramedics and officers was one of the main issues discussed by most interviewees. this challenge was reported at different levels and has been divided into three sub-categories: the lack of paramedics’ and officers’ preparedness, the lack of ems organizations’ preparedness, and the lack of community preparedness. examples of participants’ statements are given below: “... we did not know that there was an earthquake; we were afraid, but did not know what to do ...” “... we have been trained to provide services in the case of road accidents and emergency situations such as heart attacks. we did not know what to do there . . . ” “. . . we never had a maneuver that covered such a situation . . . ” “. . . people didn’t know what triage was. they didn’t know how to help us. they put a lot of pressure on us . . . ” 2the lack of coordination the most frequently discussed issue by the interviewees was the lack of coordination, which entailed internal (ems) and external (between the different relief organizations) levels. the lack of internal coordination refers to coordination in missions, dispatches, and organization of responders and equipment, and the lack of external or intersectional coordination mainly means the inconsistency of different organizations with each other in providing services. there were numerous challenges in managing and organizing relief affairs in the affected areas. rapid assessment was not carried out in the early hours of the incident, and more pressure was put on ems organizations that revealed their managers’ weakness in the allocation of equipment and human resources. “... we became involved with the police forces and the police this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 4 hit our colleagues. they insisted that we should take the corpses with us . . . ” “. . . we didn’t know where to go; the division was poor, and everyone gave a command. he said you were going to the village of varzaghan, or you go to the villages around tabriz, and so on” “. . . another problem was protection. . . ” “. . . the university had good facilities; we couldn’t serve them all though . . . ” “the security forces contacted our colleagues; unfortunately, they think we are under their control and should listen to whatever they say . . . ” “. . . the school watchman resisted opening the school . . . ” “. . . in that village, there were a few injuries, but the number of ambulances was higher . . . ” 3the challenge of managing dead bodies another challenge noted by the interviewees was the challenge of managing the dead bodies; that is, the inability to identify, organize, and transport the bodies. “. . . some of the corpses were not recognizable . . . ” “i saw an ambulance bring a corpse ...” “... we didn’t know what to do with the bodies, and people also pressured us ...” “. . . where should we put them? ...”. 4psychosocial support for the ems responders from the viewpoint of the interviewees, the lack of mental support for the ems personnel, the lack of attention to their safety and security and their families, the lack of proper water and food supply, and the presence of fear and unrest in emergency situations affected correct decision-making and deployment of responders and put the personnel in unfavorable conditions. “... i gave everything to my nephew and carried my car to varzaghan ...” “... i was able to call my family, who said they were good and safe ...” “... we were worried about our own families ...” “they said all the troops have gone to their own families’ rescue ...” “... everyone received tents and the basic necessities except our own families ...” “... after the earthquake, nobody came to us to see how we were finally doing . . . ” “... we are always neglected by the staff. . . ” 5deficiencies and the lack of facilities, equipment, supplies, and ambulances the most common problems noted by the participants included the lack of equipment, especially in the early hours after the incident, the lack of supplies and treatment facilities, the failure to supply appropriate medications to the injured, presence of inappropriate ambulances or lack of ambulances, and the lack of proper and balanced allocation of equipment to the earthquake-affected areas. “. . . there was an ambulance and we brought eight patients on it . . . ” “. . . our ambulances are sprinter and not suitable for our area . . . ” “. . . the equipment is very important. we have many shortcomings. . . ” “. . . we are not equipped with clothes. . . ” “. . . we didn’t have tags for the triage”. 6the challenge of access to villages and damaged areas reaching the villages was very difficult, and the rural texture of the earthquake-affected areas (narrow streets and rural roads) also exacerbated this problem. some road bridges were either destroyed or completely unreliable. some roads could not be crossed due to the collapse of the mountains or because they were subsiding. in the first moments, heavy traffic was created on the roads, which delayed the response. “... we went there and i saw that both the entrance and the exit were destroyed. we had to keep/stay on the bridge ...” “... there was about 30 centimeters subsidence in the direction of the road ...” “... our second problem was the traffic; after the announcement of the earthquake in these three areas, the road was actually blocked ...” “. . . on the khaje-haris path, the mountain had collapsed . . . ” 7relief volunteer and donation management the participants discussed the role of volunteers, and public and organizational donations in the process of providing relief to the injured. they also discussed problems and challenges of people’s presence in the regions, which mainly included people’s pressures to receive services, invasions to and gatherings in health centers, and interferences in the provision of health care. “. . . several trucks brought in patients . . . ” “. . . i think about 10% of the injured were brought in by ems personnel and the rest by the locals. people themselves took over the situation and did everything by themselves . . . ” “. . . people insisted that we take their patients and did not let us do triage . . . ” “. . . they disturbed our efforts for triage as soon as they saw us in our uniforms . . . ” “people came and went to help the injured trapped beneath the rubble . . . ” 8the lack of documentation of experiences almost all the ems responders had not recorded their experiences, including the actions taken, the existing problems and challenges, potential solutions, and the strengths and weaknesses of each decision and action. this lack of documentation impedes the transfer of experience to other responders and is not conducive to the improvement of weaknesses, the promotion of preparedness, the enhancement of skills, and the strengthening of management in similar future situations. “... we did not record our experiences and everything remained only in our minds; after we’re gone, there’ll be no trace of our experiences . . . ” “. . . whenever there’s an earthquake, i believe these problems will be repeated ...” “... we constantly talk about problems at our meetings, but that’s only talk . . . ” “. . . the experiences have not been transmitted even then, even if they move, they cannot solve the problem, they must work on the thoughts of managers. . . ”. 9the challenges of communicating with the earthquakeaffected areas and between teams the participants noted communication problems, including the disconnection of communication systems in the early hours and the lack of communication equipment. according this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e35 to the participants, it later became clear that communication problems had led to a lack of communication with the health centers and relief organizations. other problems in this domain included the lack of public awareness, not knowing about the center of the earthquake during the early hours, and the lack of coordination between the organizations. there was a disorder in the provision of services as a result of these shortcomings. “... landlines and cellphones were completely cut off ...” “... we were not connected anywhere; our sites were mostly wireless. we did not have any other connections with the ambulance ...” “the satellite phone does not help much . . . ” “... we couldn’t communicate with the hospitals and we didn’t know which hospitals would take in the patients ...” “... they couldn’t call us from the villages”. 10recalling and deploying ems responders the interviewees discussed some positive points in their statements, such as the good recall and dispatch of ems paramedics and the rapid receipt of donations from other provinces and neighboring cities. the high motivation and sense of responsibility in the relief forces to provide services and the spontaneous hastening of the pre-hospital personnel to help the earthquake victims were constantly discussed by the participants of this study. “. . . all our colleagues came, because everyone felt responsible . . . ” “. . . several surgeons, anesthesiologists, physicians, and nurses came . . . ” “. . . our colleagues from ardabil and meshkin shahr had reached ahar even earlier than ourselves. . . ” 4. discussion providing bls in the early phase of disasters is a key component of disaster management. following the twin earthquakes of east azerbaijan, provincial ems tried to provide bls to the injured. this qualitative study was conducted to investigate the ems response experience to the earthquake in varzaghan, haris and ahar. according to the results of the interviews, there were many challenges in the ems response to this incident, including preparedness and coordination, the challenges of managing dead bodies, psychosocial support for responders, deficiencies in supplies and ambulances, difficulty of access to rural areas, volunteer management, lack of documentation of experiences, communication challenges, and calling and deploying ems responders. in a recent study, sorani et al. reviewed the challenges of pre-hospital emergency systems in disasters. they extracted six main categories of data, and apart from the challenges of medical care, the rest of the challenges were in line with those noted in the present study (10). the six main categories of challenges in sorani’s study were people challenges, infrastructure challenges, information management system challenges, staff challenges, managerial challenges, and challenges in providing medical care. in a study by babaie et al. (2015) on the challenges of hospital response to disasters, the main challenges extracted were the lack of coordination, preparedness, equipment and supplies, which are in line with the results of this study (12). in a study by khankeh et al., the poor planning in providing health services, poor division of labor, unclear duties, overlapping tasks, parallel functioning, and poor connection between the managers and the service providers were major problems and obstacles in disaster management (13). almost all the available health sectors, including pre-hospital ems, hospitals, public health, and support departments, were involved in the response to disasters; however, there was no coordination among them (either within the ministry of health (moh) between the different departments or outside the moh), as they kept their organizational boundaries rather than reinforcing each other, although the purpose of all of them was to provide health care to all those affected by the disaster. in one study, rubin (1998) stated that the initial response to disasters should include the transfer of the injured to healthcare facilities, the recall and management of healthcare personnel, and the supply of medical equipment and other required facilities. therefore, at this stage, the main activity is to properly coordinate the storage and distribution of facilities. the management of disaster response should immediately activate all the related organizations, issue necessary permits for resource consumption, specify the priorities and progress of work, and assess and monitor the provision of services tailored to the objectives. the obtained information is collected, interpreted and explained, and the service provider should also be introduced (14). the results of the study by emami et al. (2005) entitled "strategies in evaluation and management of bam earthquake victims” revealed that a comprehensive plan is needed to ensure a comprehensive and consistent response to harmful events. a comprehensive plan affects the provision of required services for injured people and screening the victims of accidents has many benefits in their rapid and effective assessment and management (15). people develop extensive health needs due to the wide disruptions that occur after disasters (13). responding to all these needs is almost beyond the control of the health authorities, and people, themselves, should act too, irrespective of the health system in place in their country (16). in the studied earthquakes, people came to the scene from the very first moments after the incident. since the earthquake had affected a vast area –mostly rural areas– it was not possible to provide services to all of them in a limited time. the arrival of ordinary people helped quickly rescue the cathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 6 sualties from the rubble and transfer them to the health facilities. many of these people had no training in emergency services and some of the volunteers may have been harmed themselves; in fact, some of them died in the second postseismic period. in addition, their lack of awareness about the principles of service provision could have harmed other people as well. previous studies have made note of similar problems (17). one of the challenges expressed by the interviewees was that the forces active on the scene did not use the lessons learnt from the past, which demonstrates the lack of documentation of the actions and the failure to transfer them to others for future use. the lessons learned in every disaster can become the basis of training and help increase the skills and readiness of the medical personnel and the general public in the face of similar situations. therefore, by recording and documenting experiences, the level of preparedness, knowledge and skills can be raised in the community by organizing training courses for pre-hospital staff and ordinary people. in the study by khankeh et al., one of the solutions proposed for improving the services provided in critical situations was proper management, and planning and preparation based on past experiences and the information derived from regional reviews, which facilitate planning and decision-making based on actual data (18). in another study, arabs et al. also emphasized the significant relationship between the knowledge and performance of executive directors and demonstrated the importance of the development and implementation of short-term training programs to increase the knowledge and awareness of hospital executives about coping with natural disasters and hazards, including earthquakes. in addition, general training and pre-event planning help provide an effective response to health services during a disaster (19). nonetheless, these lessons are usually not taken into account for a variety of reasons (20). the lack of psychosocial support for the staff was a neglected issue in participants’ experience. the ems personnel also have their own family, who may be living in the earthquakestricken areas themselves and may have been harmed and in need of help. meanwhile, almost no action was taken to help ensure the safety of the personnel’s family, and the ems personnel had to personally ensure their family’s health and safety. furthermore, disasters create frustrating scenes that disturb the viewers’ mental health. ensuring that these issues are well taken care of requires actions that were not taken into consideration in this earthquake. similar problems were noted in previous studies. communication is one of the main infrastructures and needs of any disaster response and is one of the essential tools for establishing coordination. the first consequence of disasters is the disconnection of communication or excessive burden on the means of communication due to the increased need for communication. many disaster-responding organizations have a multi-layered communication facility for themselves, and although the pre-hospital emergency department also has a separate communication system of its own, one of the biggest drawbacks discussed in the present study was the lack of communication facilities at the time of the earthquake. the failure to plan for a rapid assessment of the health needs, dispersion and inconsistency, and prolonged data collection and analysis process mean that many decisions taken in response to emergency situations are based on previous experiences rather than actual data from the field, which was one of the problems discussed in the present study too. 5. limitations this study is being conducted 5 years after the earthquakes. the main limitation was recall bias in presenting details by the study participants. we tried to show some recorded clips of response moments to them and tried to have deep interviews for extraction of their experiences. 6. conclusion according to the research findings, the ems response to the twin earthquakes of arasbaran was a positive and successful experience in delivering emergency services regarding the presence and recall of paramedics and their sense of responsibility for providing services; however, there were challenges and weaknesses in the management and coordination of the paramedics, most of which were due to the lack of preparedness. the transfer of experiences by planning and organizing courses can address the weaknesses of the current ems system and will and help better address disasters in the future. 7. declarations 7.1. acknowledgments this study was part of an emergency medicine thesis/dissertation supported by tabriz university of medical sciences. also, this study has been funded and supported by faculty of medicine, tabriz university of medical sciences. 7.2. author contribution fgds were directed by mp, lrs transcribed and typed data. data extraction, coding and categorization were conducted by jb and lrs. paper draft was prepared by lrs and jb revised and edited it, finally all authors contributed in finalizing the manuscript. 7.3. funding and support this study was supported by tabriz university of medical sciences this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e35 7.4. conflict of interest there is no conflict of interest. references 1. babaie j, ardalan a, vatandoost h, goya mm, akbarisari a. performance assessment of communicable disease surveillance in disasters: a systematic review. plos currents. 2015;7. doi: 10.1371/currents.dis.c72864d9c7ee99ff8fbe9ea707fe4465 2. doocy s, daniels a, packer c, dick a, kirsch td. the human impact of earthquakes: a historical review of events 1980-2009 and systematic literature review. plos currents. 2013;5. doi: 10.1371/currents.dis.67bd14fe457f1db0b5433a8ee20fb833 3. guha-sapir d, vos f, below r, ponserre s. annual disaster statistical review 2011: the numbers and trends. 2012. avalable from: https://www.preventionweb.net/files/27782_adsr2011.pdf 4. cred c. natural disasters in 2017: lower mortality, higher cost. tech rep 50. 2018. available from: https://cred.be › default › files › credcrunch50. 5. khankeh hr, khorasani-zavareh d, johanson e, mohammadi r, ahmadi f, mohammadi r. disaster healthrelated challenges and requirements: a grounded theory study in iran. prehospital and disaster medicine. 2011;26(3):151-8. 6. ardalan a, kandi m, osooli m, shamseddini a, zare m, moosavand a. profile of natural hazards in ir iran. disaster and emergency health academy, iran’s national institute of health research and sph of tehran university of medical sciences; 2012. 7. djalali a, khankeh h, öhlén g, castrén m, kurland l. facilitators and obstacles in pre-hospital medical response to earthquakes: a qualitative study. scandinavian journal of trauma, resuscitation and emergency medicine. 2011;19(1):1-9. 8. catlett cl, jenkins jl, millin mg. role of emergency medical services in disaster response: resource document for the national association of ems physicians position statement. prehospital emergency care. 2011;15(3):420-5. 9. djalali a, castren m, hosseinijenab v, khatib m, ohlen g, kurland l. hospital incident command system (hics) performance in iran; decision making during disasters. scandinavian journal of trauma, resuscitation and emergency medicine. 2012;20(1):1-7. 10. sorani m, tourani s, khankeh hr, panahi s. prehospital emergency medical services challenges in disaster; a qualitative study. emergency. 2018;6(1): 1-6. 11. babaie j, moslehi s, ardalan a. rapid health needs assessment experience in 11 august 2012 east azerbaijan earthquakes: a qualitative study. plos currents. 2014;6. doi: 10.1371/currents.dis.308f6140d54f78fd1680e2b9e6460ae3 12. pouraghaei m, jannati a, moharamzadeh p, ghaffarzad a, far mh, babaie j. challenges of hospital response to the twin earthquakes of august 21, 2012, in east azerbaijan, iran. disaster medicine and public health preparedness. 2017;11(4):422-30. 13. khankeh hr, mohammadi r, ahmadi f. barriers and facilitators of health care services at the time of natural disasters. archives of rehabilitation. 2005;6(1):23-30. 14. rubin jn. recurring pitfalls in hospital preparedness and response. hospital preparation for bioterror: elsevier; 2006. p. 1-15. 15. emami mj, tavakoli ar, alemzadeh h, abdinejad f, shahcheraghi g, erfani ma, et al. strategies in evaluation and management of bam earthquake victims. prehospital and disaster medicine. 2005;20(5):327-30. 16. patterson o, weil f, patel k. the role of community in disaster response: conceptual models. population research and policy review. 2010;29(2):127-41. 17. méheux k, dominey-howes d, lloyd k. operational challenges to community participation in post-disaster damage assessments: observations from fiji. disasters. 2010;34(4):1102-22. 18. khankeh hr. national hospital disaster preparedness plan. university of welfare and rehabilitation. tehran; 2011. p. 55-76. 19. arab m, zeraati h, akbari haghighi f, ravangard r. a study on the executive managers’ knowledge and performance, and their hospitals preparedness against earthquake events and their relationships at public hospitals (affiliated by tehran university of medical sciences (tums) 2005-2006). journal of health administration. 2009;11(34):7-14. 20. donahue a, tuohy r. lessons we don’t learn: a study of the lessons of disasters, why we repeat them, and how we can learn them. homeland security affairs. 2006;2(2). avalable from: https://www.hsaj.org/articles/167 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 8 table 2: the categories and sub-categories extracted from the interviews and focused group discussions (fgds) category subcategory code lack of attention to the safety and security of the personnel’s family workers’ concerns about their families the importance of family status authorities’ failure to support the responders’ families psychological disorders developing in the personnel lack of mental support employees’ fatigue because of high volumes of work psychosocial support for the responders failure to deal with personnels’ problems after the disasters little attention to the safety and security of the responders lack of personal security fear of showing up on the field and its impact on decision-making lack of support failure to supply water and food to the responders the difficulty of decision-making in emergency situations the difficulty of making decisions in the early moments simultaneously treating several patients identification problems impossibility to identify the deceased the challenge of managing dead bodies improper handling of corpses lack of a well-developed program undefined corpse management process transporting dead bodies by ambulances instead of the injured unfamiliarity of paramedics with the basics of triage inadequate training of paramedics and the lack of necessary skills lack of ems paramedics’ and officers’ individual preparedness lack of paramedics’ readiness for providing services in disaster situations lack of preparedness personnel’s lack of familiarity with earthquake signs lack of familiarity about how to react when it is shaking lack of prior organizational preparedness lack of organizational preparedness lack of accurate planning to cover the costs of the disasters lack of readiness to confront the disasters failure to perform (between organizations and between relief agencies) lack of a disaster management office in ems people disrupting the first responders lack of familiarity of the residents with relief issues lack of community preparedness the local people’s inability to perform proper triage the people’s inability to perform medical first aids not properly equipping the responders lack of equipment lack of equipment in the early hours equipment disproportionate to geographic area lack of basic relief supplies failure to supply appropriate medications lack of supplies lack of triage tags lack of facilities, equipment, supplies, and ambulances shortage of first-aid equipment small number of ambulances in the early hours the number of ambulances being disproportionate to the mission volume in the first hours lack or presence of inappropriate ambulances ambulances being disproportionate to the region ambulances not appropriate for disaster situations lack of advanced facilities and ambulances the impossibility of helicopters landing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e35 table 2: the categories and sub-categories extracted from the interviews and focused group discussions (fgds) (continued) category subcategory code closure of rural roads and alleys lack of access due to the severe destruction of the villages the entrance of villages being obstructed lack of access to villages and damaged areas lack of access to the areas in the early hours poorly-constructed rural roads poorly-constructed regional roads geographical conditions destruction of communication routes damage to the roads and bridges road traffic and closure inviting people to help the responders transferring of injured by people community relief community members rescuing and prioritizing the injured people dominating management on the scene the abundance of public gifts managing volunteers and people’s aid community donations the existence of spontaneous help from the people people’s insistence on receiving donations themselves challenges of people’s presence on the scene the influx of people and residents into health and service centers involvement of ordinary people in therapeutic measures and triage the gathering of people and residents in health centers calling on all the ready paramedics quickly sending donations deployment of paramedics from different routes calling on and dispatch of forces rapid deployment of responders from tabriz center recalling and managing of volunteers cooperation and readiness of other provinces the arrival of auxiliary forces from neighboring cities high sense of responsibility among the personnel high motivation to provide services rapid arrival of equipment and assistance from tehran fast delivery of equipment failure to transfer experiences to other relief forces no lessons learnt from the past no lessons learnt from the past no lessons learnt from the past suspension of measures after the change of management not learning from this earthquake failure to improve post-earthquake affairs failure to act on the experiences of the ahar-haris incident lack of documenting actions not taking advantage of past experiences failure to record the response experience communication interruptions disconnection from all sources of communication in the early hours satellite phones not operating the challenges of communication with affected areas difficulty of communication with the rescue teams lack of communication equipment lack of communication equipment lack of private communication systems lack of communication equipment in ambulances lack of physical facilities for communication this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 10 table 2: the categories and sub-categories extracted from the interviews and focused group discussions (fgds) (continued) category subcategory code misalignment in missions by ambulances inconsistencies between pre-hospital and hospital emergencies lack of inter-sectional coordination uncoordinated paramedics’ decisions uncoordinated management of ambulances lack of coordination lack of full access to all the facilities available at the local level non-therapeutic intervention in treatment area lack of intra-sectional coordination unfamiliarity of the response organizations involved with each other’s tasks lack of coordination between organizations lack of coordination in supplying staffing needs lack of unity of commands relief turmoil in the affected villages lack of access to the authorities unaccountability of the officials not offering a definition of responsibility to the forces lack of time management for helping in the early hours poor allocation of paramedics to the areas collecting earthquake information by visiting the site failure to perform a quick assessment in the first hours dispersed information in the first minutes of the incident failure to perform an early initial needs assessment ems: emergency medical service this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e57 rev i ew art i c l e active and passive immunization with myelin basic protein as a method for early treatment of traumatic spinal cord injury; a meta-analysis mahmoud yousefifard1a, arian madani neishaboori1a, seyedeh niloufar rafiei alavi1, amirmohammad toloui1, mohammed i m gubari2, amirali zareie shab khaneh3, maryam karimi ghahfarokhi3, mostafa hosseini4,3∗ 1. physiology research center, iran university of medical sciences, tehran, iran. 2. community medicine, college of medicine, university of sulaimani, sulaimani, iraq. 3. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 4. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. received: june 2021; accepted: july 2021; published online: 30 august 2021 abstract: introduction: traumatic spinal cord injury (sci), as a dangerous central nervous system damage, continues to threaten communities by imposing various disabilities and costs. early adjustment of the immune system response using myelin basic protein (mbp) immunization may prevent the sci-related secondary damages. as a result, the current study is designed to review and analyse the evidence on active and passive immunization with mbp for treatment of traumatic sci. methods: medline, embase, scopus, and web of science databases were systematically searched until the end of 2020. criteria for inclusion in the current study included pre-clinical studies, which performed passive (injection of mbp-activated t cells) or active (administration of mbp or mbpmodified peptides) immunization with mbp after traumatic sci. exclusion criteria was defined as lack of a nontreated sci group, lack of evaluation of locomotion, review studies, and combination therapy. finally, analyses were conducted using stata software, and a standardized mean difference (smd) with a 95% confidence interval (ci) were reported. results: data from 17 papers were included in the present study. finally, analysis of these data showed that passive immunization (smd=0.87; 95%ci: 0.19-1.55; p=0.012) and active immunization (smd=2.08, 95%ci: 1.42-2.73; p<0.001) for/with mbp both have good efficacy in improving locomotion following traumatic sci. however, significant heterogeneity was observed in both of them. the most important sources of heterogeneity in active immunization were differences in sci models, route of administration, time interval between sci and transplantation, and type of vaccine used. in passive immunization, however, these sources were the model of sci and the time interval between sci and transplantation. although, there was substantial heterogeneity among studies, subgroup analysis showed that active immunization improved locomotion after traumatic sci in all tested conditions (with differences in injury model, severity of injury, method of administration, different time interval between sci to vaccination, etc.). conclusion: the results of the present study demonstrated that immunization with mbp, especially in its active form, could significantly improve motor function following sci in rats and mice. therefore, it could be considered as a potential treatment in acute settings such as emergency departments. however, the safety of this method is still under debate. therefore, it is recommended for future research to focus on the investigation of safety of mbp immunization in animal studies, before conducting human clinical trials. keywords: early medical intervention; emergency treatment; immunization; myelin basic protein; spinal cord injuries cite this article as: yousefifard m, madani neishaboori a, rafiei alavi s n, toloui ma, i m gubari m, zareie shab khaneh a, karimi ghahfarokhi m, hosseini m. active and passive immunization with myelin basic protein as a method for early treatment of traumatic spinal cord injury; a meta-analysis. arch acad emerg med. 2021; 9(1): e57. doi: https://doi.org/10.22037/aaem.v9i1.1316. ∗corresponding author: mostafa hosseini; department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran. email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127, orcid: https://orcid.org/0000-00021334-246x. a: first and second authors have equally contributed to this work. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 2 1. introduction spinal cord injury (sci) is one of the most dangerous neurological disorders that mostly affects the young population, and causes long-term disabilities in this group of society. unfortunately, more than 90% of the patients suffer from longterm motor disabilities and about 78% of them experience severe to moderate pain. sci and its complications impose significant direct and indirect costs on both the individual and the healthcare system; the annual costs of sci are estimated at about 26270$ per patient (1). current treatments have very low efficacy and can only alleviate some of its symptoms. medication therapy is the mainstay of current treatment methods. not only has this treatment had very little effect on motor recovery (2), but also the unwanted side effects that occur with continued use of medications are a major barrier to their use (3). current efforts in improving the recovery of central nervous system (cns) focus on two aspects: 1) stimulation of neurogenesis or regeneration and 2) neuroprotection or prevention of secondary damage (4, 5). however, there is still significant disagreement over the new treatment strategies. for instance, older studies had demonstrated that inflammation caused by autoimmune response leads to exacerbation of sci and motor impairment (6, 7). nonetheless, recent animal research showed that the postinjury autoimmune reactions provoke beneficial endogenous responses following sci (8). these studies indicate that the presence of immune t cells in the injury site increases secretion of nervous growth factors, improves the tissue environment surrounding the damaged neurons, protects the remaining myelin, and eventually, leads to enhancement of motor recovery (4). it has also been demonstrated that proper regulation of immune response following sci may have an essential role in axonal regeneration, prevention of secondary injuries, and sci recovery. in addition, local transplantation of macrophages was associated with some degree of motor recovery in the literature (9, 10). myelin basic protein (mbp) is a surface antigen expressed on cells in the cns. available studies show that transplantation of activated immune cells against this antigen is associated with improved motor recovery in animals with sci (11, 12). thus, transplantation of cells activated by this antigen, may selectively affect the cns and reduce nonspecific inflammatory responses in other tissues (13). on the other hand, administration of this protein or similar peptides, as an active immunogenic process, could have significant effects on improving motor function following sci (14-16). although several studies that evaluate the effectiveness of active and passive immunization in sci are available, conflicting findings have been reported between studies. for example, rodríguez-barrera et al. showed that active immunization with neural-derived peptides, such as mbp-related peptides, improves motor function following sci (17). however, ibara et al. showed that the use of this immunization has no effect on motor function following sci (18). these inconsistencies have made it impossible to draw a general conclusion in this regard. on the other hand, it is not yet clear which active and inactive immunogenic methods are more effective in improving the motor function of animals. accordingly, there is still no conclusion on the role of passive immunization with immune cells activated by mbp or on active immunization with injection of mbp and its derivatives in the treatment of sci in the literature. hence, the present study aims to perform a systematic review and meta-analysis to determine the effectiveness of passive or active immunization with mbp on motor recovery in animal models following sci. 2. methods 2.1. study design pico was defined as follows: problem (p) included animals in which sci injury was induced. intervention (i) was the injection of mbp-activated t cells (passive immunization) or administration of mbp or mbp-modified peptides, inducing intrinsic immunity to mbp (active immunization). comparison (c) consisted of a comparison with control animals, which were induced with sci but had not received treatment, and outcome (o) was an assessment of motor function by bbb testing. 2.2. search strategy an extensive search was conducted on medline, embase, scopus, and web of science databases until the end of 2020. search strategy was designed based on keywords related to sci and immunization/vaccination, which were obtained through searching databases such as emtree (embase) and mesh (pubmed). although only animal studies were included in the current systematic review, animal study filter was not applied in the search, in order to prevent the loss of relevant records. a manual search was also performed in the list of references of the relevant articles and highly related journals. to search for grey literature, the thesis section was searched in the proquest database. in addition, google and google scholar search engines were searched to find additional resources. finally, authors of the relevant studies were contacted to gain access to their unpublished or pre-print data. full electronic search strategy for all databases is presented in appendix 1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e57 2.3. selection criteria the inclusion criteria in the present study consisted of controlled studies that had evaluated the efficacy of immune cells activated against mbp protein in motor function improvement after sci. controlled studies were defined as studies that had a control group without any treatment (placebo group or vehicle group), in addition to the group treated with active/passive immunization with mbp. since some articles were written in chinese and japanese, no language restrictions were imposed. irrelevant, duplicate and review studies were excluded. moreover, lack of motor function evaluation and combination therapy were the other exclusion criteria in the current meta-analysis. 2.4. data collection and quality assessment the search results in the databases were combined and duplicate studies were eliminated using endnote software. next, after screening of the titles and abstracts of the records by two independent reviewers, full texts of potentially relevant studies were obtained and then relevant studies were included. the final results of the systematic search in the present study were recorded in a checklist designed based on prisma statement (19). the extracted data consisted of study design, treated and control group characteristics (age, sex, spinal cord injury model, etc.), sample size, outcome (motor outcome) and possible biases. considering that motor function recovery following sci needs a 4-week time window after the injury in a rat model, studies with a follow-up period of less than four weeks were excluded. in cases that the aforementioned information was not reported, the corresponding author of the study was contacted and asked to provide the required data. if the results were presented in the form of graphs, they were extracted using the method demonstrated by sistorm and mergo (20). in cases of disagreement between the two researchers, it would be resolved through discussion with a third reviewer. quality assessment of the studies was conducted independently by the two researchers based on the recommended syrcle guideline (21). this tool includes 10 domains of sequence generation, baseline characteristics, allocation concealment, random housing, care-giver blinding, random outcome assessment, blinding of outcome assessor, incomplete outcome assessment, selective outcome assessment, and other risk of bias. two independent reviewers rated each domain (as low risk, high risk, unclear) according to signaling questions presented in explanation and elaboration paper of syrcle guideline (21). any disagreement was resolved by discussion. 2.5. statistical analysis in all of the studies, the scores of the animals in the bbb test in treated and control groups were considered as the final outcome. data were recorded as mean and standard deviation and analyzed using “metan” command in stata 14.0 statistical software. the findings were reported as standardized mean difference (smd) and 95% confidence interval (95% ci). heterogeneity between the studies was assessed using the i2 test and a p value of less than 0.1 was considered as significant heterogeneity. if the studies were homogeneous, the fixed effect model was performed, and in case of heterogeneity, subgroup analysis was conducted to determine the source of the heterogeneity. random effect model was performed in cases where the cause of heterogeneity was not clear. meta-analyses were performed, only if the data were reported in at least two separate experiments. finally, publication bias was investigated by performing egger’s test and presenting a funnel plot (22). 3. results 3.1. study characteristics searching the databases eventually provided researchers with 1055 non-duplicate records. by reviewing the abstracts and titles of the records, the full text of 40 relevant articles were obtained and then studied in detail. finally, the data of 17 articles (5, 11, 12, 14-18, 23-30) were included in the present meta-analysis (figure 1). these pre-clinical articles consisted of 39 separate analyses (experiments), 36 of which were performed on rats and 3 were performed on mice. the animals were female in 38 of the experiments and male in only one. the models for the induction of sci were contusion in 31, compression in four, hemisection in one and transection model in three experiments. the severity of injury was moderate in 22 and severe in 17 of the trials. the site of injury was thoracic in all of the experiments. seven experiments had used prophylaxis vaccination and 32 of them performed the vaccination after the sci. 25 experiments vaccinated the subjects immediately after the sci. 13 experiments conducted passive immunization by injecting mbp-activated t cells, while 26 experiments performed active immunization. compounds used to induce active immunization included mbp, a91 (a peptide derived from mbp), and dendritic cells pulsed with mbp or a91. moreover, follow-up time ranged from 27 days to 112 days (table 1). 3.2. efficacy of passive immunization on motor function recovery after sci the effect of passive immunization on improving the motor function of animals following sci was investigated in 13 experiments. meta-analysis showed that passive immunization improved motor function of animals after sci (smd = 0.87; 95% ci: 0.19, 1.55; p = 0.012). significant heterogeneity was observed in this section (i2 = 78.4%; p <0.001) (figure 2). therefore, subgroup analysis was conducted. the most imthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 4 portant sources of heterogeneity and subgroup analysis results are reported in table 2. the model of injury and the time interval between sci and transplantation were the most important sources of heterogeneity. studies that used transection/hemisection models (i2 = 0.0%) and had a time interval of 1-9 days between sci and transplantation (i2 = 49.9%) were found to be homogeneous. interestingly, the efficacy of passive immunization on motor recovery was affected by the diversities between the studies. passive immunization improved motor function only in models of contusion injury (smd = 1.23, p <0.001), whereas such an effect was not observed in transection/hemisection models (smd = -0.19; p = 0.565). also, the use of passive immunization in severe sci models had no effect on motor function of the animals (smd = 0.47, p = 0.262), but in moderate injuries, it significantly enhanced motor function (smd = 1.30, p = 0.018). in addition, intraperitoneal injection of mbp-activated t cells (smd = 0.54, p = 0.173) and the administration of this treatment immediately after sci (smd = 0.77, p = 0.052) had no effect on the motor function of animals. finally, the impression is created that the positive effects of passive immunization is only observed in long term followup (p = 0.024) (table 2). 3.3. efficacy of active immunization on motor function recovery after sci the effect of active immunization on the motor function of the animals was evaluated in 26 experiments. meta-analysis of this section demonstrated that active immunization significantly improves motor function following sci (smd = 2.08, 95% ci: 1.42, 2.73; p <0.001) (figure 3). significant heterogeneity was observed in this part (i2 =86.4%, p <0.001). subgroup analysis showed that differences in sci model, route of administration, time interval between sci and transplantation, and the type of vaccine inducing active immunization were the most important sources of heterogeneity. studies that had used compression model to induce sci (i2 = 0.0%), studies with intraperitoneal (i2 = 26.9%) or intrathecal administration (i2 = 0.0%), studies that performed immunization in the chronic phase (60 days after sci) (i2 =16.8%), and studies that had used activated dendritic cells to create immunization (i2 = 0.0%) were homogeneous. it is worth mentioning that active immunization improved the motor function in the animals in all test conditions (with differences in injury model, severity of injury, method of administration, etc.) (table 3). 3.4. publication bias and risk of bias assessment the syracle tool was used to assess the risk of bias in the included studies. accordingly, all of the studies in this review had low risk of bias in the baseline characteristic section. on the other hand, all of the articles had an unclear risk of bias on random housing. in both care giver blinding and allocation concealment items, there was one study with unclear risk of bias, three had low risk of bias, and the others were classified as having high risk of bias. however, only two studies had high risk of bias in the blinding of outcome assessor section and the others were classified as having low risk of bias. more information on the risk of bias of the articles is shown in table 4. it should be kept in mind that publication bias was not observed in either active immunization (p = 0.131) or passive immunization studies (p = 0.272) (figure 4). 4. discussion the present study aimed to determine the efficacy of passive and active immunization with mbp on motor function recovery following sci in animal models. the obtained results showed that overall, both passive and active immunization with mbp can improve motor function recovery following sci in rats and mice. this substantiates previous findings in the literature indicating the positive effects of controlled activity of the immune system in the injury site. in other words, the autoimmunity that occurs due to the activation of immune cells, (including t-helper 2, macrophages, and neutrophils), protects the spinal cord from further damage, whilst promoting tissue recovery (10, 11, 31). based on the results of the current review, in general, active immunization has a greater effect on the protection and recovery of the spinal cord following injury, compared to passive immunization. this finding is very promising, as storage of antigens in the laboratory and the clinic is much more attainable than activated immune cells. furthermore, injection of antigens is associated with less complications and side effects. previous studies have also noted the pathogenic effect of most injected t cells on the central nervous system (32). in addition, the formation of memory cells in active immunization provides a more durable immunity and it is expected to protect the injured spinal cord from further damage for a longer time. it has even been observed that in chronic conditions (60 days after injury) the cells formed under the influence of active immunization could maintain their function and lead to recovery after spinal cord injury (17). subgroup analysis showed that passive immunization is not effective in promoting motor recovery after sci in severe or immediate administration after the injury. hence, their administration is not recommended in such conditions. in contrast, active immunization is less associated with the acuity of the injury and has significant efficacy in all conditions. this statement could be justified considering the vulnerability of cells to antigens (10). it may even be suggested that in situations in which immunization is achieved by the injection of dendritic cells, the immunity is safer and more long lasting, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e57 granted that the immune cells become activated inside the body of the animal itself (12, 23, 26). at last, it should be added that immunization, and especially active immunization, have shown favorable efficacy in animal studies. further investigations are recommended to focus on the application of this method both for the treatment of sci (23, 25, 27-30) and also prophylaxis (vaccination) (14, 15, 18) in high-risk groups, e.g. horse riders or rally drivers. however, the safety of this method is still under debate, as autoimmune diseases, such as multiple sclerosis, are caused by hyperreaction to intrinsic antigens, such as mbp (33). this issue may also be considered as one of the limitations of the present study, as none of the included studies had discussed it. however, there are studies that demonstrate the beneficial effects observed when administrating t cell vaccines in multiple sclerosis patients (34). hence, investigations on the safety of active/passive vaccination with mbp are strongly suggested to be carried out before conducting clinical trials. moreover, another limitation of this study was the heterogeneity of the articles. considering the sources of this heterogeneity, including the method of injury, the time interval between sci and treatment, and the route of administration, it is proposed that further research should be undertaken regarding the mentioned variables. finally, due to the mentioned limitations, conclusions about the application of active and passive immunization in sci should be drawn with caution. 5. conclusion although the heterogeneity among the included studies in the present meta-analysis was significant, the result of this study showed that the immunization provided with mbp, especially in its active form, significantly improves motor function following sci in rats and mice. however, future investigations are necessary in order to establish the efficacy of this method. in addition, safety of immunization with mbp is debated, both in active and passive immunization. hence, considering the possible complications of this method, such as autoimmunity, it is recommended for future researchers to investigate its safety by designing more animal experiments, before conducting clinical trials. 6. declarations 6.1. conflict of interest there is no conflict of interest. 6.2. funding this study has been funded and supported by sina trauma and surgery research center, tehran university of medical sciences, tehran, iran; grant no: 95-01-38-31334. 6.3. authors’ contribution study design: mh, my; data gathering: my, amn, snra, at; analysis: mh, azsk, and mkg my; interpreting the results: all authors; drafting: my, amn; critically revised: all authors. 6.4. acknowledgments none. references 1. mann r, schaefer c, sadosky a, bergstrom f, baik r, parsons b, et al. burden of spinal cord injury-related neuropathic pain in the united states: retrospective chart review and cross-sectional survey. spinal cord. 2013;51(7):564-70. 2. backonja mm, irving ga, argoff c. rational multidrug therapy in the treatment of neuropathic pain. curr pain headache rep. 2006;10:34-8. 3. marineo g, iorno v, gandini c, moschini v, smith tj. scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. journal of pain and symptom management. 2012;43(1):87-95. 4. hauben e, butovsky o, nevo u, yoles e, moalem g, agranov e, et al. passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. the journal of neuroscience. 2000;20(17):6421-30. 5. jones tb, ankeny dp, guan z, mcgaughy v, fisher lc, basso dm, et al. passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats. the journal of neuroscience. 2004;24(15):3752-61. 6. hausmann o. post-traumatic inflammation following spinal cord injury. spinal cord. 2003;41(7):369-78. 7. brambilla r, bracchi-ricard v, hu w-h, frydel b, bramwell a, karmally s, et al. inhibition of astroglial nuclear factor kb reduces inflammation and improves functional recovery after spinal cord injury. the journal of experimental medicine. 2005;202(1):145-56. 8. donnelly dj, popovich pg. inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. experimental neurology. 2008;209(2):378-88. 9. yoles e, hauben e, palgi o, agranov e, gothilf a, cohen a, et al. protective autoimmunity is a physiological response to cns trauma. the journal of neuroscience. 2001;21(11):3740-8. 10. moalem g, leibowitz–amit r, yoles e, mor f, cohen ir, schwartz m. autoimmune t cells protect neurons from secondary degeneration after central nervous system axothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 6 tomy. nature medicine. 1999;5(1):49-55. 11. wang hj, hu jg, shen l, wang r, wang qy, zhang c, et al. passive immunization with myelin basic protein activated t cells suppresses axonal dieback but does not promote axonal regeneration following spinal cord hemisection in adult rats. the international journal of neuroscience. 2012;122(8):458-65. 12. wang y, li j, kong p, zhao s, yang h, chen c, et al. enhanced expression of neurotrophic factors in the injured spinal cord through vaccination with myelin basic protein-derived peptide pulsed dendritic cells. spine. 2015;40(2):95-101. 13. liu h, shiryaev sa, chernov av, kim y, shubayev i, remacle ag, et al. immunodominant fragments of myelin basic protein initiate t cell-dependent pain. journal of neuroinflammation. 2012;9:119. 14. hauben e, butovsky o, nevo u, yoles e, moalem g, agranov e, et al. passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. the journal of neuroscience : the official journal of the society for neuroscience. 2000;20(17):6421-30. 15. ibarra a, sosa m, garcía e, flores a, cruz y, mestre h, et al. prophylactic neuroprotection with a91 improves the outcome of spinal cord injured rats. neuroscience letters. 2013;554:59-63. 16. rodríguez-barrera r, fernández-presas am, garcía e, flores-romero a, martiñón s, gonzález-puertos vy, et al. immunization with a neural-derived peptide protects the spinal cord from apoptosis after traumatic injury. biomed research international. 2013;2013:827517. 17. rodríguez-barrera r, flores-romero a, garcía e, fernández-presas am, incontri-abraham d, navarrotorres l, et al. immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury. cns neuroscience and therapeutics. 2020;26(6):6508. 18. ibarra a, hauben e, butovsky o, schwartz m. the therapeutic window after spinal cord injury can accommodate t cell-based vaccination and methylprednisolone in rats. the european journal of neuroscience. 2004;19(11):298490. 19. moher d, liberati a, tetzlaff j, altman dg. preferred reporting items for systematic reviews and meta-analyses: the prisma statement. annals of internal medicine. 2009;151(4):264-9. 20. sistrom cl, mergo pj. a simple method for obtaining original data from published graphs and plots. american journal of roentgenology. 2000;174(5):1241-4. 21. hooijmans cr, rovers mm, de vries rbm, leenaars m, ritskes-hoitinga m, langendam mw. syrcle’s risk of bias tool for animal studies. bmc medical research methodology. 2014;14(1):43. 22. egger m, smith gd, schneider m, minder c. bias in meta-analysis detected by a simple, graphical test. bmj. 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from spinal cord injury in mice. spinal cord. 2009;47(5):360-6. 27. lü hz, xu l, zou j, wang yx, ma zw, xu xm, et al. effects of autoimmunity on recovery of function in adult rats following spinal cord injury. brain, behavior, and immunity. 2008;22(8):1217-30. 28. martiñon s, garcía e, flores n, gonzalez i, ortega t, buenrostro m, et al. vaccination with a neural-derived peptide plus administration of glutathione improves the performance of paraplegic rats. the european journal of neuroscience. 2007;26(2):403-12. 29. martiñón s, garcía e, gutierrez-ospina g, mestre h, ibarra a. development of protective autoimmunity by immunization with a neural-derived peptide is ineffective in severe spinal cord injury. plos one. 2012;7(2):e32027. 30. martiñón s, garcía-vences e, toscano-tejeida d, flores-romero a, rodriguez-barrera r, ferrusquia m, et al. long-term production of bdnf and nt-3 induced by a91-immunization after spinal cord injury. bmc neuroscience. 2016;17(1):42. 31. schwartz m, raposo c. protective autoimmunity: a unifying model for the immune network involved in cns repair. the neuroscientist. 2014;20(4):343-58. 32. held w, meyermann r, qin y, mueller c. perforin and tumor necrosis factor α in the pathogenesis of experimental allergic encephalomyelitis: comparison of autoantigen induced and transferred disease in lewis rats. journal of autoimmunity. 1993;6(3):311-22. 33. zang yc, li s, rivera vm, hong j, robinson rr, breitbach wt, et al. increased cd8+ cytotoxic t cell responses to myelin basic protein in multiple sclerosis. the journal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e57 of immunology. 2004;172(8):5120-7. 34. zhang j, medaer r, stinissen p, hafler d, raus j. mhc-restricted depletion of human myelin basic protein-reactive t cells by t cell vaccination. science. 1993;261(5127):1451-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 8 appendix 1: search syntaxes for current study pubmed ((immunization[mesh] or active immunization*[mesh] or passive immunization*[mesh] or vaccination[mesh] or autoimmunity[mesh] or immunization, passive/methods[mesh] or immunization[tiab] or active immunization*[tiab] or passive immunization*[tiab] or vaccination[tiab] or autoimmunity[tiab] or immunization, passive/methods[tiab] or autoimmunities[tiab] or autoimmune response*[tiab] or myelin basic protein[tiab] or immunization with neural derived peptides[tiab] or a91[tiab])) and (spinal cord injuries[mh] or spinal cord contusion[tiab] or spinal cord transection[tiab] or injured spinal cord[tiab] or spinal cord traum*[tiab] or spinal cord hemisection[tiab] or spinal compression[tiab] or traumatic myelopath*[tiab] or spinal cord laceratio*[tiab] or post-traumatic myelopath*[tiab]) embase 1’active immunization’/exp or ’passive immunization’/exp or ’vaccination’/exp or ’myelin basic protein’/exp 2’spinal cord injury’/exp or ’experimental spinal cord injury’/exp or ’spinal cord transsection’/exp or ’cervical spinal cord injury’/exp or ’cervical spinal cord injury’/exp or ’cervical spinal cord injury’/exp or ’lumbar spinal cord’/exp or ’photochemical spinal cord injury’/exp or ’spinal paralysis’/exp or ’spinal cord transverse lesion’/exp 3#1 and #2 scopus ( ( title-abs-key ( "active immunization" ) or title-abs-key ( "passive immunization" ) or title-abs-key ( "vaccination" ) or title-abs-key ( "myelin basic protein" ) or title-abs-key ( "myelin basic protein" ) or title-abs-key ( "immunization with neural derived peptides" ) or title-abs-key ( "a91" ) ) ) and ( ( ( title-abs-key ( "spinal cord injuries" ) or title-abs-key ( "spinal cord injury" ) or title-abs-key ( "spinal cord transection" ) or title-abs-key ( "spinal cord hemisection" ) or titleabs-key ( "injured spinal cord" ) or title-abs-key ( "spinal cord trauma" ) or title-abs-key ( "spinal compression" ) or titleabs-key ( "spinal cord contusion" ) or title-abs-key ( "photochemical spinal cord injury" ) or title-abs-key ( "spinal paralysis" ) ) ) ) web of science ((ts="active immunization" or "passive immunization" or "vaccination" or "myelin basic protein" or "myelin basic protein" or "immunization with neural derived peptides" or "a91") and (ts="spinal cord injuries" or "spinal cord injury" or "spinal cord transection" or "spinal cord hemisection" or "injured spinal cord" or "spinal cord trauma" or "spinal compression" or "spinal cord contusion" or "photochemical spinal cord injury" or "spinal paralysis") ) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e57 table 1: characteristics of included studies study sex, strain, species severity of injury; model; injury location injury to treatment* (day) vaccine number of administrations type of treatment transplantation route number of cells followup days hauben, 2000 (14) female, lewis, rat severe; contusion, transection; t9, t7 -7, 0, 7 tmbp cells, mbp-ifa 1 passive, active ip, sc 1.0 × 107 76 hauben, 2003 (23) female, lewis, rat severe; contusion; t8 0 dc-mbp, dc-a91 1 active is, iv, sc 5.0 × 105 1.0 × 107 2.0 × 107 76 hu, 2012 (24) female, lewis, rat moderate; contusion; t9 9 tmbp cells 1 passive iv 4.0 × 105 49 hu, 2016 (25) female, lewis, rat moderate; contusion; t9 0 t-helper 1 mbp cell, t-helper 2 mbp cell 1 passive iv 2.0 × 107 42 ibarra, 2004 (18) female, lewis and sd, rat severe; contusion; t9 -7 a91-cfa 1 active sc na 72 ibarra, 2013 (15) female, sd, rat moderate; contusion; t9 -40 a91-cfa 1, 2 active sc na 63 jones, 2004 (5) female, lewis, rat moderate, severe; contusion, transection; t8 -7, 0 tmbp cells, mbp-ifa, mbp-cfa 1 passive, active ip, sc 1.0 × 107 43, 63 liu, 2009 (26) nr, balb/c, mice moderate; compression; t10 1 dc-mbp 1 active ip, is 5.0 × 105 84 lu, 2008 (27) female and male, sd, rat moderate; contusion; t9 0 tmbp cells 1 passive iv 2.0 × 107 56 martinon, 2007 (28) female, sd, rat moderate; contusion, compression; t9 0 a91-cfa 1, 2 active sc na 77, 84 martinon, 2013 (29) female, sd, rat moderate, severe; contusion, transection; t9 0 a91-cfa 1 active sc na 56 martinon, 2016 (30) female, sd, rat moderate; contusion; t9 0 a91-cfa 1 active sc na 112 rodríguezbarrera, 2013 (16) female, sd, rat moderate; contusion; t9 0 a91-cfa 1 active sc na 30 rodríguezbarrera, 2020a (17) female, sd, rat moderate; contusion; t9 60 a91 2 active sc na 60 rodríguezbarrera, 2020b (17) female, sd, rat moderate; contusion; t9 60 a91-cfa 1 active sc na 60 wang, 2012 (11) female, sd, rat severe; transection; t9 0 tmbp cells 1 passive iv 2.0 × 107 56 wang, 2015 (12) nr, balb/c, mice moderate; compression; t9 1 dc-a91 1 active ip 1.0 × 106 27 cfa: complete freund’s adjuvant; dc: dendritic cells; dc-mbp: dcs pulsed with myelin basic protein; dc-a91: dcs pulsed with a91 peptide; ifa: incomplete freund’s adjuvant; ip: intraperitoneal; is: intraspinal; iv: intravenous; mbp: myelin basic protein; na: not applicable; sc: subcutaneous; sd: sprague-dawley; t: thoracic regions; tmbp: myelin basic protein-activated t cells; mbp-ifa: mbp emulsified in incomplete freund’s adjuvant; mbp-cfa: mbp emulsified in complete freund’s adjuvant. *, negative numbers refer to pre-treatment protocols. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 10 table 2: subgroup analysis for effect of passive immunization with myelin basic protein (mbp) on motor function recovery after spinal cord injury (sci) variable no. experiment heterogeneity (p value) smd (95% ci) p model of injury contusion 10 81.1% (<0.001) 1.23 (0.39, 2.07) <0.001 transection/hemisection 3 0.0% (0.796) -0.19 (-0.81, 0.45) 0.565 severity of injury moderate 6 84.6% (<0.001) 1.39 (0.24, 2.55) 0.018 severe 7 71.3% (0.002) 0.47 (-0.35, 1.30) 0.262 route of administration intraperitoneal 7 68.7% (0.004) 0.54 (-0.24, 1.32) 0.173 intravenous 6 85.7% (<0.001) 1.33 (0.10, 2.56) 0.034 time interval between sci and transplantation immediately after sci 11 79.6% (<0.001) 0.77 (-0.006, 1.55) 0.052 1-9 days after sci 2 49.9% (0.158) 1.38 (0.32, 2,44) 0.011 follow-up duration < 8 weeks 4 80.0% (0.002) 0.51 (-0.50, 1.52) 0.327 ≥ 8 weeks 15 80.1% (<0.001) 1.11 (0.14, 2.07) 0.024 ci: confidence interval; smd: standardized mean difference. table 3: subgroup analysis for effect of active immunization with myelin basic protein (mbp) on motor function recovery after spinal cord injury (sci) variable no. experiment heterogeneity (p value) smd (95% ci) p model of injury contusion 21 88.5% (<0.001) 2.42 (1.61, 3.23) <0.001 compression 4 0.0% (0.567) 1.28 (0.72, 1.84) <0.001 transection 1 na na na severity of injury moderate 16 90.1% (<0.001) 2.67 (1.68, 3.68) <0.001 severe 10 68.9% (0.001) 1.27 (0.59, 1.95) <0.001 route of administration intraperitoneal 2 26.9% (0.242) 1.49 (0.40, 2.90) 0.008 intravenous 1 na na na subcutaneous 19 89.8% (<0.001) 2.29 (1.44, 3.14) <0.001 intraspinal 4 0.0% (0.981) 1.64 (1.01, 2.27) <0.001 time interval between sci and transplantation prophylaxis 7 88.4% (<0.001) 1.50 (0.28, 2.71) 0.016 immediately after sci 17 87.3% (<0.001) 2.42 (1.52, 3.31) <0.001 60 days after sci 2 16.8% (0.273) 1.94 (1.10, 2,77) <0.001 type of vaccine mbp or a91 base antigens 18 90.1% (<0.001) 1.11 (0.85, 1.36) <0.001 activated dendritic cells 8 0.0% (0.446) 1.73 (1.23, 2.22) <0.001 follow-up duration < 8 weeks 4 81.1% (<0.001) 5.12 (0.50, 9.73) 0.030 ≥ 8 weeks 21 95.8% (<0.001) 1.67 (1.10, 2.24) <0.001 ci: confidence interval; smd: standardized mean difference. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e57 table 4: risk of bias assessment of included studies study sequence generation baseline characteristics allocation concealment random housing caregiver blinding random outcome assessment blinding of outcome assessor incomplete outcome assessment selective outcome assessment other hauben, 2000 p p p ? p p p p ? p hauben, 2003 p p ? ? ? p p p ? p hu, 2012 p ? p p p p p hu, 2016 p ? p p p p ibarra, 2004 p ? ? ? ? ibarra, 2013 p ? p p ? ? jones, 200 p p ? p p p ? ? liu, 2009 p p p ? p p p p ? p lu, 2008 ? p ? ? ? p p martinon, 2007 p ? p ? ? ? martinon, 2013 p ? p ? ? ? martinon, 2016 p p ? p p ? ? p rodríguezbarrera, 2013 p ? p ? ? ? rodríguezbarrera, 2020a p p p ? p p p p ? p rodríguezbarrera, 2020b ? p ? p p ? ? p wang, 2012 p p ? p p ? ? p wang, 2015 ? p ? p ? ? p p : low risk of bias; ?: unclear risk of bias; -: high risk of bias figure 1: flowchart of selecting related studies this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 12 figure 2: forest plot for effect of passive immunization with myelin basic protein (mbp) on motor function recovery after spinal cord injury. smd: standardized mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e57 figure 3: forest plot for effect of active immunization with myelin basic protein (mbp) on motor function recovery after spinal cord injury. smd: standardized mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 14 figure 4: funnel plot for assessment of publication bias in studies assessing the effect of passive and active immunization with myelin basic protein (mbp) on motor function recovery after spinal cord injury. smd: standardized mean difference. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e34 or i g i n a l re s e a rc h diagnostic accuracy of abdominal wall ultrasonography and local wound exploration in predicting the need for laparotomy following stab wound ali vafaei1, kamran heidari1, afshin saboorizadeh1, amin shams akhtari1∗ 1. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: december 2016; accepted: december 2016; published online: 11 january 2017 abstract: introduction: screening of patients with anterior abdominal penetrating trauma in need for laparotomy is an important issue in management of these cases. this study aimed to compare the accuracy of abdominal wall ultrasonography (awu) and local wound exploration (lwe) in this regard. methods: this diagnostic accuracy study was conducted on âl’ě 18 year-old patients presenting to emergency department with anterior abdominal stab wound and stable hemodynamics, to compare the characteristics of awu and lwe in screening of patients in need of laparotomy. results: 50 cases with the mean age of 28.44 ± 7.14 years were included (80% male). sensitivity, specificity and area under the receiver operating characteristic (roc) curve of awu were 70.58 (95% ci: 44.04 – 88.62), 93.33 (95% ci: 76.49 – 98.83), and 81.96 (95% ci: 69.91 – 94.01), respectively. these measures were 88.23 (62.25 – 97.93), 93.33 (76.49 – 98.83), and 90.78 (95% ci: 81.67 – 99.89) for lwe, respectively. the difference in overall accuracy of the two methods was not statistically significant (p = 0.0641). conclusion: based on the findings of the present study, awu and lwe had the same specificity but different sensitivities in screening of anterior abdominal stab wound patients in need of laparotomy. the overall accuracy of lwe was slightly higher (91.48% versus 85.1%). keywords: abdominal injuries; wounds, penetrating; wounds, stab; ultrasonography; diagnostic techniques and procedures © copyright (2017) shahid beheshti university of medical sciences cite this article as: vafaei a, heidari k, saboorizadeh a, shams akhtari a. diagnostic accuracy of abdominal wall ultrasonography and local wound exploration in predicting the need for laparotomy following stab wound. emergency. 2017; 5(1): e34. 1. introduction p enetrating abdominal trauma is known as one of the relatively frequent causes of emergency department visits. there is a general agreement that patients with penetrating abdominal trauma and hemodynamic instability must immediately be referred to operation room without additional diagnostic measures (1). however, management of hemodynamically stable patients is a controversial issue. at least 25% of anterior abdominal stab wounds are superficial and do not need laparotomy (2). unnecessary laparotomy can increase the risk of morbidity and mortality of these patients (3). sanei et al. showed that 82% of stab wound laparotomies, which were done only based on anterior fascial ∗corresponding author: amin shams akhtari; emergency department, loghman hakim hospital, kamali street, karegar avenue, tehran, iran. tel: +989123788731 / fax: +982155415539 / e-mail: amin.may1981@gmail.com impairment, are negative (4). in recent years, most physicians have tried to change their diagnostic approaches from mandatory exploration to selective diagnostic approaches (5-7). appropriate approach to these patients needs balance between invasiveness and accuracy of diagnostic measures in this regard. using ultrasonography, deep peritoneal lavage (dpl), serial clinical examination, local wound exploration (lwe), and abdominal computed tomography (ct) scan are suggested by different studies to decrease the rate of unnecessary laparotomies. lwe is a valid, yet invasive, screening tool for selection of stab wound patients in need of laparotomy (2). however, abdominal wall ultrasonography (awu) seems to be as a non-invasive, available, bedside, and safe alternative for lwe in this regard (1, 3). based on the abovementioned point, this study aimed to assess the diagnostic accuracy of awu and lwe in detection of patients in need of laparotomy following anterior abdominal stab wound. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 2 2. methods 2.1. study design and setting this cross sectional study was conducted on patients presenting to emergency departments of loghman hakim, imam hossein, and hafte-tir hospitals, tehran, iran, following anterior abdominal stab wound, during march 2013 to march 2015, to compare the diagnostic accuracy of awu and lwe in prediction of need for laparotomy. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences and informed consent form was signed by all participants. authors adhered to all helsinki recommendations and confidentiality of patients’ information during the study period. 2.2. participants patients older than 18 years old with anterior abdominal stab wound were included. hemodynamic instability, presenting peritoneal signs, protrusion of abdominal organs, gastrointestinal bleeding, pregnancy, instrument in situ, presence of abdominal free fluid on focused abdominal ultrasonography for trauma patients (fast), peritoneal evisceration, multiple wounds, and need for emergent laparotomy were among the exclusion criteria. anterior abdominal wall was defined as the area superior to the inguinal ligaments, medial to the anterior axillary line, and two fingerbreadths inferior to the costal margins. 2.3. data gathering a predesign check list, consisting of demographic information (age, sex), trauma mechanism, vital signs (blood pressure, heart rate, respiratory rate, and oxygen saturation), findings of awu and lwe regarding need for laparotomy, as well as final outcome (decision of in charge surgeons regarding performing laparotomy), was used for data gathering. without interfering in the routine approach, eligible patients underwent awu by a trained senior emergency medicine resident (under supervision of an emergency medicine specialist) at the time of admission to emergency department. the emergency medicine resident was trained and certified by an expert radiologist, performing tract ultrasonography on ten sheep cadaver models under his direct supervision. after doing awu, all patients underwent lwe by senior surgery residents and were followed until discharge from hospital. patients that underwent laparotomy based on final decision of in charge surgeon, considering all clinical and imaging findings (serial clinical examination, abdominal ct scan, serial fast, and etc.) during the period of hospital admission were considered as reference group. samsung hm70a ultrasonography machine with 8 mhz linear probe was used for ultrasonography of the abdominal wall and its 10 × 10 cm surrounding area (figure 1). figure 1: abdominal wall ultrasonography view. 2.4. statistical analysis considering 25% prevalence of penetrating abdominal trauma in need for laparotomy (2), d = 0.05, and 95% confidence interval (ci), the minimum required sample size was calculated to be 35 cases. data were analyzed using spss version 21 and stata 11. qualitative and quantitative variables were presented with frequency and percentage, and mean ± standard deviation, respectively. for evaluating the screening performance characteristics of awu and lwe in prediction of need for laparotomy sensitivity, specificity, posthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e34 table 1: baseline characteristics of studied patients (n = 50) variable number (%) age (year) 18 -24.9 12 (24) 2534.9 23 (46) ≥ 35 15 (30) sex male 40 (80) female 10 (20) marital status married 18 (38.3) single 29 (61.7) trauma mechanism knife 41 (82) other 9 (18) employment employed 36 (72) non-employed 14 (28) vital sign systolic blood pressure (mmhg) 117.10 ± 10.79 diastolic blood pressure (mmhg) 71.30 ± 9.36 heart rate (/minute) 87.62 ± 6.97 respiratory rate (/minute) 19.20 ± 1.84 oxygen saturation (%) 96.52 ± 1.50 data are presented as mean ± standard deviation or frequency and percentage. figure 2: area under the receiver operating characteristic (roc) curve of abdominal wall ultrasonography and local wound exploration in prediction of need for laparotomy following anterior abdominal stab wound (p = 0.0641). itive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr), and negative likelihood ratio (nlr) with 95% ci were calculated. the area under the receiver operating characteristic (roc) curve of the two tests was compared. need for laparotomy based on final decision of in charge surgeon was considered as the reference test. pvalues less than 0.05 were assumed significant results. 3. results 3.1. baseline characteristics 50 cases with the mean age of 28.44 ± 7.14 years (18 – 47) were included (80% male). table 1 shows the baseline characteristics of studied patients. 46% of cases were in 25 – 35 years age group, 61.7% single, 72% employee, and 82% with knife. 3 (6%) cases were discharged against medical advice and were omitted from final analysis. 3.2. screening characteristics based on awu and lwe 14 (28%) and 17 (34%) cases were detected as peritoneal penetration and needed laparotomy. according to the final decision of surgery service based on all clinical and imaging findings, 17 (34%) cases underwent laparotomy during the hospitalization period. table 2 and figure 2 summarize the screening performance characteristics of awu and lwe in prediction of need for laparotomy following anterior abdominal stab wound. the area under the roc curve of awu and lwe were 81.96 (95% ci: 69.91 – 94.01) and 90.78 (95% ci: 81.67 – 99.89), respectively (p = 0.0641). 4. discussion based on the findings of the present study, awu and lwe have the same specificity (93.3%) but different sensitivities (70.58% versus 88.23%) in screening of anterior abdominal stab wound patients in need of laparotomy. the overall accuracy of lwe in this regard is slightly higher (91.48% versus 85.1%) without statistical significance. rapid assessment and decision making plays a main role in improving the outcome of severely injured trauma patients (8-11). although using lwe could be helpful in eliminating hospitalization of more than 30% of patients with anterior abdominal stab wound (2), it is invasive, uncomfortable for the patient, and difficult in obese and uncooperative patients as well as those with thick abdominal musculature. finding noninvasive alternatives for lwe is an interesting area in management of these patients in emergency and surgery departments. ultrasonography is known as an available diagnostic measure for focused assessment of blunt and penetrating trauma patients in emergency department (12-17). omari et al. showed that ultrasonography is a good guide for selecting patients in need for laparotomy following penetrating abdominal trauma (1). murphy et al. reported that tract ultrasonography in patients with anterior abdominal penetrating trauma had 59% sensitivity and 100% specificity (18). soffer et al. reported that sonography had 48% sensitivity and 98% specificity in diagnosis of intra-abdominal lesions and fray et al. reported 100% positive and negative predictive value of ultrasonography in this regard (19, 20). ku et al. presented a 76 year-old stab wound case with negative abdominal ct scan findings, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 4 table 2: screening performance characteristics of abdominal wall ultrasonography (awu) and local wound exploration (lwe) in prediction of need for laparotomy following anterior abdominal stab wound (n = 47) characteristics awu lwe true positive 12 (25.5) 15 (31.9) true negative 28 (59.6) 28 (59.6) false positive 2 (4.2) 2 (4.2) false negative 5 (10.6) 2 (4.2) sensitivity 70.58 (44.04 – 88.62) 88.23 (62.25 – 97.93) specificity 93.33 (76.49 – 98.83) 93.33 (76.49 – 98.83) positive predictive value 85.71 (56.15 – 97.48) 88.23 (62.25 – 97.93) negative predictive value 84.84 (67.33 – 94.28) 93.33 (76.49 – 98.83) positive likelihood ratio 6.00 (1.63 – 22.03) 7.50 (2.01 – 27.88) negative likelihood ratio 0.17 (0.07 –0.40) 0.07 (0.01 – 0.27) data are presented with 95% confidence interval. which underwent laparoscopy based on positive tract ultrasonography finding regarding peritoneal impairment (21). in our study, need for laparotomy was confirmed in 85.7% of patients with positive awu and 88.2 % of positive lwe results. there were 5 (10.6%) cases with false negative ultrasonography reports and 2 (4.2%) cases with false negative exploration reports. although the difference in total accuracy of the two models is not statistically significant, accuracy of exploration is in excellent range and ultrasonography in good range. as we know, ultrasonography is very operator dependent and this slight inferiority of ultrasonography could be eliminated by more practice. it seems that tract ultrasonography as a bedside, noninvasive, non-expensive, available, and safe diagnostic approach could be considered for screening of penetrating abdominal trauma patients in need of laparotomy. 5. limitation among the limitations of the present study is not evaluating the cases with multiple penetrating traumas and those with trauma of other parts of the abdominal area. in addition, in most cases trauma was caused by knife, which affects the diversity of trauma type and might limit the generalizability of the results for cases such as wounds caused by bullets. patient selection for laparotomy was done by surgeons who were aware of the results of lwe, which might have led to some type of selection bias. 6. conclusion based on the findings of the present study, awu and lwe have the same specificity (93.3%) but different sensitivities (70.58% versus 88.23%) in screening of anterior abdominal stab wound patients in need of laparotomy. the overall accuracy of lwe is slightly higher (91.48% versus 85.1%) without statistical significance. 7. appendix 7.1. acknowledgements the authors would like to thank all the staff of loghman hakim, hafte tir, and imam hossein hospitals and clinical research development center of loghman hakim hospital, for their cooperation. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. omari a, bani-yaseen m, khammash m, qasaimeh g, eqab f, jaddou h. patterns of anterior abdominal stab wounds and their management at princess basma teaching hospital, north of jordan. world journal of surgery. 2013;37(5):1162-8. 2. cothren cc, moore ee, warren fa, kashuk jl, biffl wl, johnson jl. local wound exploration remains a valuable triage tool for the evaluation of anterior abdominal stab wounds. the american journal of surgery. 2009;198(2):223-6. 3. ku c-y, chang c-j, huang c-y, sun j-t, lin h-f, lin ms, et al. a novel role of ultrasonography in identification of the tract of abdominal stab injury. critical ultrasound journal. 2014;6(1):1. 4. sanei b, mahmoudieh m, talebzadeh h, shahabi shahmiri s, aghaei z. do patients with penetrating abdomithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e34 nal stab wounds require laparotomy? arch trauma res. 2013;2(1):21-5. 5. tsikitis v, biffl wl, majercik s, harrington dt, cioffi wg. selective clinical management of anterior abdominal stab wounds. american journal of surgery. 2004;188(6):807-12. 6. shaftan g. indications for operations in abdominal trauma. american journal of surgery. 1960;99:657-64. 7. demetriades d, rabinowitz b. indications for operation in abdominal stab wounds. a prospective study of 651 patients. annals of surgery. 1987;205(2):129-32. 8. walcher f, kortum s, kirschning t, weihgold n, marzi i. [optimized management of polytraumatized patients by prehospital ultrasound]. der unfallchirurg. 2002;105(11):986-94. 9. clarke jr, trooskin sz, doshi pj, greenwald l, mode cj. time to laparotomy for intra-abdominal bleeding from trauma does affect survival for delays up to 90 minutes. the journal of trauma. 2002;52(3):420-5. 10. walcher f, weinlich m, conrad g, schweigkofler u, breitkreutz r, kirschning t, et al. prehospital ultrasound imaging improves management of abdominal trauma. the british journal of surgery. 2006;93(2):238-42. 11. gunst m, ghaemmaghami v, sperry j, robinson m, o’keeffe t, friese r, et al. accuracy of cardiac function and volume status estimates using the bedside echocardiographic assessment in trauma/critical care. the journal of trauma. 2008;65(3):509-16. 12. bokhari f, nagy k, roberts r, brakenridge s, smith r, joseph k, et al. the ultrasound screen for penetrating truncal trauma. the american surgeon. 2004;70(4):31621. 13. feliciano dv, rozycki gs. the management of penetrating abdominal trauma. advances in surgery. 1995;28:139. 14. conrad mf, patton jh, jr., parikshak m, kralovich ka. selective management of penetrating truncal injuries: is emergency department discharge a reasonable goal? the american surgeon. 2003;69(3):266-72; discussion 73. 15. blaivas m. triage in the trauma bay with the focused abdominal sonography for trauma (fast) examination. the journal of emergency medicine. 2001;21(1):41-4. 16. udobi kf, rodriguez a, chiu wc, scalea tm. role of ultrasonography in penetrating abdominal trauma: a prospective clinical study. the journal of trauma. 2001;50(3):475-9. 17. vassiliadis j, edwards r, larcos g, hitos k. focused assessment with sonography for trauma patients by clinicians: initial experience and results. emergency medicine. 2003;15(1):42-8. 18. morphy j, hall j, provost d. facial ultrasound for evaluation of anterior bdominal stab wound injury. j of trauma. 2005;5(4):843-6. 19. fry wr, smith rs, schneider jj, organ ch, jr. ultrasonographic examination of wound tracts. archives of surgery. 1995;130(6):605-7; discussion 8. 20. soffer d, mckenney mg, cohn s, garcia-roca r, namias n, schulman c, et al. a prospective evaluation of ultrasonography for the diagnosis of penetrating torso injury. the journal of trauma. 2004;56(5):953-7; discussion 7-9. 21. ku c-y, chang c-j, huang c-y, sun j-t, lin h-f, lin ms. a novel role of ultrasonography in identification of the tract of abdominal stab injury. critical ultrasound journal. 2014;6:30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 174 emergency (2014); 2 (4): 174-177 brief report clinical presentation and microbial analyses of contact lens keratitis; an epidemiologic study seyed ahmad rasoulinejad1, mahmoud sadeghi2, mohammad montazeri3*, hesam hedayati goudarzi4, mahmood montazeri3, nadali akbarian5 1. department of ophthalmology, babol university of medical sciences, babol, iran 2. infectious diseases research center, babol university of medical sciences, babol, iran 3. young researchers club, islamic azad university, babol branch, babol, iran 4. department of ophthalmology, ahvaz jundishapur university of medical sciences, ahvaz, iran 5. school of nursing and midwifery, babol university of medical sciences, babol, iran abstract introduction: microbial keratitis is an infective process of the cornea with a potentially and serious visual impairments. contact lenses are a major cause of microbial keratitis in the developed countries especially among young people. therefore, the purpose of the present study was to evaluate the frequency and microbiological characteristic of clk in patients referred to the emergency department (ed) of teaching hospitals, babol, iran. methods: this is a cross-sectional study of all patients with contact lens induced corneal ulcers admitted to the teaching hospitals of babol, iran, from 20112013. an ophthalmologist examined patients with the slit-lamp and clinical features of them were noted (including pain, redness, foreign body sensation, chemosis, epiphora, blurred vision, discomfort, photophobia, discharge, ocular redness and swelling). all suspected infectious corneal ulcers were scraped for microbial culture and two slides were prepared. data were analyzed using spss software, version 18.0. results: a total of 14 patients (17 eyes) were recruited into the study (100% female). the patients’ age ranged from 16-37 years old (mean age 21.58±7.23 years). the most prevalent observed clinical signs were pain and redness. three samples reported as sterile. the most common isolated causative organism was pseudomonas aeroginosa (78.6%), staphylococcus aureus 14.3%, and enterobacter 7.1%, respectively. treatment outcome was excellent in 23.5%, good in 47.1%, and poor in 29.4% of cases. conclusion: improper lens wear and care as well as the lack of awareness about the importance of aftercare visits have been identified as potential risk factors for the corneal ulcer among contact lens wearers. training and increasing the awareness of adequate lens care and disinfection practices, consulting with an ophthalmologist, and frequent replacement of contact lens storage cases would greatly help reducing the risk of microbial keratitis. key words: keratitis; contact lenses; ophthalmology, epidemiology, anti-bacterial agents cite this article as: rasoulinejad sa, sadeghi m, montazeri m, hedayati goudarzi h, montazeri m, akbarian n. clinical presentation and microbial analyses of contact lens keratitis; an epidemiologic study. emergency. 2014;2(4):174-7. introduction: 1 icrobial keratitis is an infective process of the cornea with a potentially sight-threatening condition and serious visual impairments (1). untreated or severe keratitis may lead to significant public health problems like perforation of cornea and endophthalmitis (2, 3). contact lenses are a major cause of microbial keratitis in the developed countries especially among young people with about 12% hospitalized cases requiring corneal transplantation (4, 5). contact lenses may reduce the epithelial barrier function by interfering with normal epithelial cell proliferation and differentiation. with the growth of soft contact lens *corresponding author: mohammad montazeri; young researchers club, islamic azad university, babol branch, babol, iran. tel: +981112415102; email: mm.montazeri@gmail.com received: july 2014; accepted: july 2014 wear, the incidence of this problem raised globally (3, 6). there are several differences in the incidence of contact lens keratitis (clk) across the world (7). pseudomonas aeruginosa can adhere to the surface of the contact lens and colonize during wear and survive in contact lens storage cases. these processes maybe lead to corneal ulcers; a severe infection can cause permanent blindness (8). although corneal ulcer is a rare complication of contact lens wear, increasing in the number of lens wearers and the risk of blindness, provide important reasons to evaluate patients with contact lens induced corneal ulcers (9, 10). the number of contact lens wearers has dramatically increased in iran, particularly among young adults in recent years. therefore, the purpose of the present study was to evaluate the frequency and microbiological characteristic of clk in m mailto:mm.montazeri@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 175 rasoulinejad et al patients referred to the emergency department (ed) of teaching hospitals, babol, iran. methods: study design and patients this is a cross-sectional study of all patients with contact lens induced corneal ulcers who were referred to the ed of teaching hospitals, babol, iran, from 2011 to 2013. patients were excluded from the study with a previous history of anterior segment surgery, treatment for ocular surface disorders, use of any topical ocular medications, or noninfectious corneal ulcers include autoimmune, neurotropic, toxic, and marginal keratitis. an ophthalmologist examined patients with the slitlamp and clinical features of them were noted (including pain, redness, foreign body sensation, chemosis, epiphora, blurred vision, discomfort, photophobia, discharge, ocular redness and swelling). all patients wore soft contact lenses, either conventional daily or disposable extended wear contact lenses. the use of disinfection solution (hydrogen peroxide formulations) was also asked from patients and registered. informed consent form was received from all participants. sampling, culture, and susceptibility tests after a detailed ocular examination, all suspected infectious corneal ulcers were scraped for microbial culture and susceptibility studies initiated before treatment. after instillation of 0.5% proparacaine hydrochloride, two slides were prepared by an ophthalmologist for the direct microscopic examination using flame-sterilized kimura spatula or a sterile 21 gauge needle, from the leading edge and the bed of the ulcer. the obtained materials were spread onto labeled slides for gram and giemsa stains and also inoculated using cotton swab applicators onto the surfaces of blood agar, chocolate agar, and sabouraud agar plates (for fungal infection assay). if bacterial growth was observed in the media, the culture considered as positive and the resistance to antibiotics determined by the mueller-hinton media, too. results were interpreted according to the guidelines of the national committee on clinical laboratory standards (nccls) (11). visual acuity any reduction in vision was tested using snellen letter charts and measured in comparison with the unaffected eye. however, when both eyes were affected, the amount of vision loss was calculated using the worse eye and a standard reference of 6/6 snellen acuity. similarly, if there was amblyopia in the unaffected eye, the standard reference of 6/6 was used for analogy. visual acuity was categorized as no light perception (nlp), counting fingers (cf), hand motion (hm), loss of two or more lines, and no loss of vision. definitions clk is defined as a supportive corneal infiltrate and overlying epithelial defect with the recent history of contact lens use, with or without hypopyon. the ulcer size gives an estimate area of the ulcer to calculate the analysis more easily as follow: size of ulcer = length × breadth / mm2. disease duration was defined based on the number of days that symptoms were experienced. duration of hospitalization was referred to the length of stay in hospital. visual outcome when the corneal healing was not associated with visual loss, the visual outcome considered as “excellent”, in patients had < 2 lines loss of visual acuity as “good”; and for loss ≥ 2 lines or patients underwent penetrating keratoplasty as “poor”. statistical analysis data were analyzed using the spss statistical software version 18.0. quantitative data were expressed as mean ± standard deviation and qualitative ones as frequency and percentage. results: 14 patients (17 eyes) were recruited into the study who all of them were female. the patients’ age ranged from 16-37 years old (with mean ± standard deviation 21.58±7.23). the mean lag time between the onset of symptoms and the first time patients referred to the ed was 48 hours. the mean treatment duration was 29±7 days in outpatient and 96±21 days in inpatient cases. 64.3% were treated outpatient, 28.6% admitted, and 7.1% needed surgical intervention. keratitis involved the right eye in seven cases (41.2%) and the left eye in five ones (29.4%). infection was bilateral in five patients (29.4%), too. all 14 patients were contact lens wearers; there were two cases (14.3%) of therapeutic contact lens and 12 (85.7%) of cosmetic lens users. overnight lens users were noted in four referees. four of the 12 (75%) cosmetic contact lens wearers were table 1: clinical characteristics of patients with contact lens microbial keratitis  sign and symptom number (%) pain and redness 14 (100) foreign body sensation 11 (78.6) chemosis 11 (78.6) epiphora 10 (71.4) decreased visual acuity 9 (64.2) hypopyon 5 (35.7) size of the corneal ulcer <3 mm2 9 (52.9) eyes ≥3 mm2 8 (47.1) eyes visual acuity hand motion 4 (28.6) finger count 4 (28.6) >1/10 snellen acuity 6 (42.8) causative organism pseudomonas aeroginosa 11 (78.6) staphylococcus aureus 2 (14.3) enterobacter 1 (7.1) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 176 emergency (2014); 2 (4): 174-177 using lenses of another person in time of the infectious event. all cosmetic contact lens wearers chose and wore their lenses without any consultation with ophthalmologists, and 10 (71.4%) subjects applied no disinfection regimen of contact lenses. the most prevalent observed clinical signs were pain and redness that reported in all patients. table 1 shows the clinical characteristics of patients with clk. the mean size of ulcer was 3.92±2.11 mm2. there were three samples reported as sterile. the most causative microorganism was pseudomonas aeroginosa (78.6%). table 2 indicates the antibiogram results that 71.4% of the microorganisms were sensitive to ciprofloxacin, whereas ceftazidime, imipenem, and meropenem considered as the second most effective antibiotics. treatment outcome was excellent in 23.5%, good in 47.1%, and poor in 29.4% of cases. discussion: the most prevalent observed clinical signs were pain and redness and the most common causative microorganism of clk was pseudomonas aeroginosa. treatment outcome was excellent in 23.5%, good in 47.1%, and poor in 29.4% of cases. mela et al. in a retrospective study reported 23 patients with contact lensrelated keratitis. all of patients were using soft contact lenses from three days to 20 years (12). in a study by malaysian national eye database study group, 202 patients were notified to the contact-lens related microbial keratitis registry with a mean age of 26.7 years (71.8% female), during 2007-2008, while all of them wore soft contact lens (13). evaluation of 56 ulcerative keratitis subjects associated with contact lens wearing showed that contact lens-associated ulcers were seen in 86% of those wearing soft lenses (14). benhmidoune et al. conducted a descriptive study of 51 patients presented to the ophthalmology hospital in casablanca with contact lens-related microbial keratitis; the mean age of patients was 22 years, with a sex ratio of 7.5 female to male (15). in the present study all patients contacted with lens wearers and there were 2 and 12 cases of therapeutic contact lens and cosmetic lens users, respectively. the overnight and extended wear of contact lens is known as a risk factor for microbial keratitis (16). the microorganisms found from the corneal scrapes were not part of the ocular flora and their presence demonstrated that the source of contamination was external (17). it has been shown that some microorganisms including potentially pathogenic species can survive for hours on contact lenses and have harmful effects on the ocular surface (8). here, it was found that pseudomonas is the dominant causative agent in contact lensrelated microbial keratitis, accounting for more than 75% of the culture-positive specimens. previous studies revealed that pseudomonas aeruginosa is the most common microorganism in contact lensrelated microbial keratitis, followed by gram-positive bacteria, fungi, and acanthamoeba (12-15, 18, 19). pseudomonas aeruginosa was the most frequent isolated pathogen in 60% and 79.7% of clk cases of mela et al. and goh et al. study, respectively (12, 13). in benhmidoune et al. study corneal bacterial cultures were positive in 47.8% of subjects pathogens found were staphylococcus aureus, pseudomonas aeruginosa, and acanthamœba (15). pseudomonas was the most common isolate, presented in 13 (23%) of the 56 cases in galantine et al study (14). staphylococcus species were the second most common pathogen in 11 (20%) of the 56 cases. findings of the present study demonstrated on the importance of referral of all contact lens wearers with suspected corneal infection to ophthalmologists for further treatment. improper lens wear and care as well as the lack of awareness about the importance of aftercare visits have been identified as risk factors for the corneal ulcer among contact lens wearers. training and increasing the awareness of adequate lens care and disinfection practices of users, consulting with an ophthalmologist, and frequent replacement of contact lens storage cases would greatly help reducing the risk of microbial keratitis. conclusion: improper lens wear and care as well as the lack of awareness about the importance of aftercare visits have table 2: antibiotic sensitivity and resistance pattern of microorganism isolated from corneal ulcers in patients with microbial keratitis  antibiotic pseudomonas aeruginosa staphylococcus aureus enterobacter sensitive n (%) resistant n (%) sensitive n (%) resistant n (%) sensitive n (%) resistant n (%) penicillin 0 (0) 11 (100) 0 (0) 2 (100) 0 (0) 1 (100) ciprofloxacin 9 (81.8) 2 (18.2) 0 (0) 2 (100) 1 (100) 0 (0) gentamycin 0 (0) 11 (100) 2 (100) 0 (0) 1 (100) 0 (0) amikacin 5 (45.5) 6 (54.5) 1 (50) 1 (50) 1 (100) 0 (0) ceftazidime 9 (81.8) 2 (18.2) 0 (0) 2 (100) 1 (100) 0 (0) cefixime 0 (0) 11 (100) 0 (0) 2 (100) 1 (100) 0 (0) imipenem 9 (81.8) 2 (18.2) 0 (0) 2 (100) 1 (100) 0 (0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 177 rasoulinejad et al been identified as potential risk factors for the corneal ulcer among contact lens wearers. training and increasing the awareness of adequate lens care and disinfection practices, consulting with an ophthalmologist, and frequent replacement of contact lens storage cases would greatly help reducing the risk of microbial keratitis. acknowledgments: we would like to thank all staffs of ophthalmology departments of babol university of medical sciences, babol, iran. conflict of interest: the authors declared no conflict of interests. funding support: none authors’ contributions: none references: 1. fong cf, tseng ch, hu fr, wang ij, chen wl, hou yc. clinical characteristics of microbial keratitis in a university hospital in taiwan. am j ophthalmol. 2004;137(2):329-36. 2. lam j, tan g, tan dt, mehta js. demographics and behaviour of patients with contact lens-related infectious keratitis in singapore. ann acad med singapore. 2013;42(10):499-506. 3. upadhyay mp, srinivasan m, whitcher jp. microbial keratitis in the developing world: does prevention work? int ophthalmol clin. 2007;47(3):17-25. 4. keay l, edwards k, naduvilath t, et al. microbial keratitis predisposing factors and morbidity. ophthalmology. 2006;113(1):109-16. 5. hoddenbach jg, boekhoorn ss, wubbels r, vreugdenhil w, van rooij j, geerards aj. clinical presentation and morbidity of contact lens-associated microbial keratitis: a retrospective study. graefes arch clin exp ophthalmol. 2014;252(2):299306. 6. mah-sadorra jh, yavuz sg, najjar dm, laibson pr, rapuano cj, cohen ej. trends in contact lens-related corneal ulcers. cornea. 2005;24(1):51-8. 7. pacella e, la torre g, de giusti m, et al. results of casecontrol studies support the association between contact lens use and acanthamoeba keratitis. clin ophthalmol. 2013;7:991-4. 8. szczotka-flynn lb, pearlman e, ghannoum m. microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review. eye contact lens. 2010;36(2):116-29. 9. evans dj, fleiszig sm. microbial keratitis: could contact lens material affect disease pathogenesis? eye contact lens. 2013;39(1):73-8. 10. haghighi sho, begi hrm, sorkhabi r, tarzamani mk, zonouz gk, mikaeilpour a. diagnostic accuracy of ultrasonography in detection of traumatic lens dislocation. emergency. 2014;2(3):[in press]. 11. kiehlbauch ja, hannett ge, salfinger m, archinal w, monserrat c, carlyn c. use of the national committee for clinical laboratory standards guidelines for disk diffusion susceptibility testing in new york state laboratories. j clin microbiol. 2000;38(9):3341-8. 12. mela ek, giannelou ip, koliopoulos jx, gartaganis sp. ulcerative keratitis in contact lens wearers. eye contact lens. 2003;29(4):207-9. 13. goh pp, shamala r, chandamalar s, tai xy. contact lens-related corneal ulcer: a two-year review. med j malaysia. 2010;65 suppl a:120-3. 14. galentine pg, cohen ej, laibson pr, adams cp, michaud r, arentsen jj. corneal ulcers associated with contact lens wear. arch ophthalmol. 1984;102(6):891-4. 15. benhmidoune l, bensemlali a, bouazza m, et al. contact lens related corneal ulcers: clinical, microbiological and therapeutic features. j fr ophtalmol. 2013;36(7):594-9. 16. garg p. diagnosis of microbial keratitis. br j ophthalmol. 2010;94(8):961-2. 17. bharathi mj, ramakrishnan r, meenakshi r, kumar cs, padmavathy s, mittal s. ulcerative keratitis associated with contact lens wear. indian j ophthalmol. 2007;55(1):64-7. 18. stapleton f, keay lj, sanfilippo pg, katiyar s, edwards kp, naduvilath t. relationship between climate, disease severity, and causative organism for contact lens-associated microbial keratitis in australia. am j ophthalmol. 2007;144(5):690-8. 19. wang ag, wu cc, liu jh. bacterial corneal ulcer: a multivariate study. ophthalmologica. 1998;212(2):126-32. emergency. 2017; 5 (1): e40 br i e f re p o rt protocol adherence in prehospital medical care provided for patients with chest pain and loss of consciousness; a brief report mostafa mehrara1, nader tavakoli1, marzieh fathi1∗, babak mahshidfar1, mohammad amin zare1, azita asadi1, saeedeh hosseinzadeh1, mehdi safdarian1 1. department of emergency medicine, hazrat-e-rasoul akram medical centre, iran university of medical sciences, tehran, iran. received: may 2016; accepted: august 2016; published online: 11 january 2017 abstract: introduction: although many protocols are available in the field of the prehospital medical care (pmc), there is still a notable gap between protocol based directions and applied clinical practice. this study measures the rate of protocol adherence in pmc provided for patients with chest pain and loss of consciousness (loc). methods: in this cross-sectional study, 10 educated research assistants audited the situation of provided pmc for non-traumatic chest pain and loc patients, presenting to the emergency department of a tertiary level teaching hospital, compare to national recommendations in these regards. results: 101 cases with the mean age of 56.7 ± 12.3 years (30-78) were audited (55.4% male). 61 (60.3%) patients had chest pain and 40 (39.7%) cases had loc. protocol adherence rates for cardiac monitoring (62.3%), o2 therapy (32.8%), nitroglycerin administration (60.7%), and aspirin administration (52.5%) in prehospital care of patients with chest pain were fair to poor. protocol adherence rates for correct patient positioning (25%), o2 therapy (75%), cardiac monitoring (25%), pupils examination (25%), bedside glucometery (50%), and assessing for naloxone administration (55%) in prehospital care of patients with loc were fair to poor. conclusion: there were more than 20% protocol violation regarding prehospital care of chest pain patients regarding cardiac monitoring, o2 therapy, and nitroglycerin and aspirin administration. there were same situation regarding o2 therapy, positioning, cardiac monitoring, pupils examination, bedside glucometery, and assessing for naloxone administration of loc patients in prehospital setting. keywords: emergency medical services; protocol adherence; chest pain; unconsciousness; medical audit © copyright (2017) shahid beheshti university of medical sciences cite this article as: mehrara m, tavakoli n, fathi m, mahshidfar b, zare m, asadi a, hosseinzadeh s, safdarian m. protocol adherence in prehospital medical care provided for patients with chest pain and loss of consciousness; a brief report. emergency. 2017; 5 (1): e40. 1. introduction prehospital medical care (pmc) is a vital component of medical care system which affects the outcome of whole health system by saving the patient’s golden time-to-treatment and changing his prognosis especially in patients with potentially life-threatening complaints like chest pain (1-3). because of the importance of providing on-time high-quality pmc, several national and international evidence-based guidelines are prepared for emergency medical services (ems) staff which advocate a particular course of action in clinical care and help to choose and perform the most ∗corresponding author: marzieh fathi; emergency department, hazrate-rasoul akram hospital, satarkhan st, niyayesh st, tehran, iran. email: marziehfathi@yahoo.com effective interventions as prompt as possible (4). while pre-determined consensus instructions are available widely, there is still a notable gap between protocol based directions and applied clinical practice of ems staff (5-7). this gap may result in incomplete or inappropriate care providing and increased morbidity and mortality. thus measuring the rate of protocol adherence is a useful tool for evaluating the quality and comprehensiveness of medical care delivered in prehospital settings and probing the protocols to find the potential defects and insufficiencies which may lead to protocol violation by care providers. there are different studies evaluating the rate of protocol adherence in prehospital and hospital environments and patients with different clinical situations (like cardiac arrest, traumatic brain injury, sepsis, myocardial infarction, seizure, asthma and etc.) (7-12). in our knowledge this is the first study in our country which this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. mehrara et al. 2 measures the rate of protocol adherence in prehospital care provided for patients with chief complaints of chest pain and loss of consciousness in an urban public referral system. 2. methods 2.1. study design and setting this cross-sectional single-center study was conducted in a tertiary level teaching hospital with total annual census of 40,000 adult patients in may-june 2013. study was approved by the institutional ethics committee (faculty of medicine, iran university of medical sciences) and carried out in accordance with declaration of helsinki (1989). informed written consent was obtained from patients or their legal guardians to use their data. 2.2. participants we enrolled conveniently the ≥18 year old patients with chief complaints of non-traumatic chest pain and loss of consciousness who was transferred to hospital by public ems and admitted in our emergency department. patients who had taken any medical care in other facilities before transferring to our hospital and patients who had used any medications before the arrival of ems were excluded from study. patients who had experienced cardiac arrest and needed the use of prehospital cardiac arrest protocol and patients with specific known or highly probable causes of loss of consciousness (like head trauma and intoxications) were excluded from study. 2.3. procedure for evaluating the protocol adherence 10 research assistants who were medical students were educated and informed about the national protocols for essential medical care which should be delivered to patients in prehospital setting in a 4-hour didactic course. in this course they became familiar with a checklist consisted of questions about the basic elements of protocol(s) which should be used by ems care providers in approaching the patients with chest pain and loss of consciousness. then they completed the checklist for 15 ems transported patients under supervision of an emergency physician. these 15 patients were not included in study. after completing the preliminary checklists, these research assistants attended in different clinical day and night shifts in emergency department and evaluated the protocol adherence in provided prehospital care by checking the items considered in checklists. in challenging cases or items, they consulted with on-duty emergency physician. in patients with chief complaint of non-traumatic chest pain the most important items of our national protocol which should be evaluated were: measuring and documenting the blood pressure, beginning the cardiac monitoring and oxygen-therapy, maintaining a peripheral intra-venous line, administrating nitroglycerine and aspirin in cases suspicious to acute coronary syndrome, assessing the probability of pneumothorax (by auscultation the lung sounds) (14). in patients with chief complaint of loss of consciousness the most important items of our national protocol which should be evaluated were: assessing the airway and the patient’s need to airway management and performed interventions in this domain including the use of manual maneuvers to orotracheal intubation, beginning the cardiac monitoring and supplemental oxygen, putting the patient in anti-aspiration position, performing bedside glucometery, examining the pupil size, administrating the naloxone and 50% dextrose (if indicated) (14). 3. results: pmc of 137 patients were studied (80 patients with nontraumatic chest pain and 57 patients with loss of consciousness). 36 cases were exclude because of following criteria: 2 patients had experienced prehospital arrest and resuscitated by ems staff, 16 patients had received medical care in another facility before calling ems, 11 patients had used sublingual nitroglycerine before calling ems, 3 cases with loss of consciousness were very suspicious to opium overdose, 1 case was suspicious to have tri-cyclic antidepressant overdose (depending on their history), and 3 cases had suspicious history of head trauma. finally 101 cases were enrolled for analysis. 3.1. baseline characteristics pmc of 101 cases with the mean age of 56.7 ± 12.3 years (3078) were audited (55.4% male). 61 (60.3%) patients had chest pain and 40 (39.7%) cases had loc. 35 (34.6%) of patients had previous history of ischemic heart disease, 27 (26.7%) diabetes mellitus, 30 (29.7%) hypertension, 12 (11.8%) hyperlipidemia, 6 (5.9%) drug/substance abuse. 3.2. data analysis minimum needed sample size was calculated as 101 patients according to “n=t2pq / (p*δ)2” formula. all data analyses were performed with spss version 18 (spss, inc., chicago, il, usa). continuous numerical data were reported as mean ± standard deviation and categorical variables were presented with frequency and percentage. the adherence rates were categorized into five groups based on likert scale: ≥ 90% as excellent, 80-90% good, 70-80% fair, 60-70% weak and < 60% poor. 3.3. protocol adherence table 1 and 2 summarize the results of analysis regarding the protocol adherence rates of provided pmc for patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e40 table 1: protocol adherence rate of provided prehospital medical care for patients with chest pain (n=61) protocol based instruction adherence rate assessing the probability of pneumothorax 61 (100.0) beginning the cardiac monitoring 38 (62.3) measurement of vital signs 58 (95.1) beginning the oxygen therapy 20 (32.8) peripheral intravenous line 59 (96.7) line is open and working 54 (91.5) line does not work 5 (8.4) administration of nitroglycerine 37 (60.7) administration of aspirin 32 (52.5) data were presented as frequency and percentage. table 2: protocol adherence rate of provided prehospital medical care for patients with loss of consciousness (n=40) protocol based instruction adherence rate airway management 36 (90.0) correct patient positioning 10 (25.0) beginning the oxygen therapy 30 (75.0) beginning the cardiac monitoring 10 (25.0) measurement of vital signs 40 (100.0) examining the pupils 10 (25.0) peripheral intravenous line 40 (100.0) line is open and working 38 (95.0) line does not work 2 (5.0) bedside glucometery 20 (50.0) assessing the indication of naloxone 22 (55.0) data were presented as frequency and percentage. with chest pain and loc. protocol adherence rates for cardiac monitoring (62.3%), o2 therapy (32.8%), nitroglycerin administration (60.7%), and aspirin administration (52.5%) in prehospital care of patients with chest pain were fair to poor. protocol adherence rates for correct patient positioning (25%), o2 therapy (75%), cardiac monitoring (25%), pupils examination (25%), bedside glucometery (50%), and assessing for naloxone administration (55%) in prehospital care of patients with loc were fair to poor. 4. discussion: based on the results of present study, protocol adherence regarding cardiac monitoring, o2 therapy, and nitroglycerin and aspirin administration in prehospital care of chest pain patients were fair to poor. regarding pre hospital care of loc patients, there were fair to poor protocol adherence for patient positioning, o2 therapy, cardiac monitoring, pupils examination, bedside glucometery, and assessing for naloxone administration. except some limited items like assessing the probability of pneumothorax and airway management, other protocol based instructions are not followed by ems staff. even vital signs measurements are not done completely and available simply-provided cares like oxygen therapy are not provided satisfactorily. our study showed also that the interventions both in monitoring and treatment sectors are under-mentioned by ems staff and beginning cardiac monitoring is as neglected as administration of nitroglycerine and aspirin in patients with chest pain. according to our results, patients in loss of consciousness group received less medical care in prehospital setting than patients with chest pain. this is while the approach to patients with both complaints are illustrated in available step-by-step well established protocols which are taught tremendously in almost all clinical courses implemented for ems staffs. our findings about oxygen therapy is compatible with the findings of hale et al who showed in their study that although oxygen use in ambulances is a very common daily procedure, protocol adherence in its use in suboptimal especially in some patients like patients with chronic obstructive pulmonary diseases (13). the protocol violation has been issued in other studies too. for example a retrospective study on paramedic compliance with advanced cardiac life support (acls) epinephrine guidelines in 75 out-of-hospital cardiac arrest showed that only 14% of patients received epinephrine in accordance with current acls guidelines (13). another study by johansson et al showed that in the majority of outof-hospital cardiac arrest cases epinephrine is not administhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. mehrara et al. 4 tered according to current acls guidelines and the adherence to guidelines is lower in out-of-hospital cardiac arrest than in in-hospital ones (13). similar studies on quality of out-of-hospital resuscitation showed similar results. as the wik et al showed in their study on out-of-hospital resuscitation that chest compressions were not delivered half of the time, most of delivered compressions were too shallow and patients’ golden time was wasted without trying to do the chest compressions, electrocardiographic analysis, defibrillation or any other interventions (6). this is while most studies on this era have shown that protocol adherence can improve the management and clinical outcomes of patients (1416). protocol violation is not a problem only in prehospital setting and it is also seen in emergency department and other inpatients settings (17). some efforts (like presence of a pharmacist on the resuscitation team, simplification of protocols, changing the protocols, etc.) have been done to improve the compliance with guidelines but none of them are approved in this era (18). for better conclusion in this regard performing a complete kap (knowledge, attitude, practice) study with larger sample size could be helpful. therefore, more attention in this field and theoretical and practical training courses in this field seems to be helpful. 5. conclusion there were more than 20% protocol violation regarding prehospital care of chest pain patients regarding cardiac monitoring, o2 therapy, and nitroglycerin and aspirin administration. there were same situation regarding o2 therapy, positioning, cardiac monitoring, pupils examination, bedside glucometery, and assessing for naloxone administration of loc patients in prehospital setting. 6. appendix 6.1. acknowledgements authors would like to thank all the staff of emergency department of shohaday-e 7 tir hospital, tehran, iran. 6.2. authors contribution mostafa mehrara, nader tavakoli, babak mahshidfar: study design. azita asadi, saeedeh hoseinzade, mahdi safdarian: case enrollment. marzieh fathi, mohammad amin zare: data analysis and preparing the manuscript for publication. all authors declare that they had been read the final draft and their responsibility for all part of study. 6.3. conflict of interest there is no conflict of interest between authors. 6.4. funding this study has not been funded any institution. references 1. mathew t, menown i, mccarty d, gracey h, hill l, adgey a. impact of pre-hospital care in patients with acute myocardial infarction compared with those first managed in-hospital. european heart journal. 2003;24(2):161-71. 2. cantor wj, hoogeveen p, robert a, elliott k, goldman le, sanderson e, et al. prehospital diagnosis and triage of st-elevation myocardial infarction by paramedics without advanced care training. american heart journal. 2012;164(2):201-6. 3. quinn t, johnsen s, gale 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emergency care: results of resca+ 31 registry. archives of cardiovascular diseases. 2012;105(5):262-70. 16. goldstein p, wiel e. management of prehospital thrombolytic therapy in st-segment elevation acute coronary syndrome (< 12 hours). minerva anestesiologica. 2005;71(6):297-302. 17. pham jc, kelen gd, pronovost pj. national study on the quality of emergency department care in the treatment of acute myocardial infarction and pneumonia. academic emergency medicine. 2007;14(10):856-63. 18. draper hm, eppert ja. association of pharmacist presence on compliance with advanced cardiac life support guidelines during in-hospital cardiac arrest. annals of pharmacotherapy. 2008;42(4):469-74. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e21 https://doi.org/10.22037/aaem.v9i1.1155 or i g i n a l re s e a rc h echocardiographic abnormalities as independent prognostic factors of in-hospital mortality among covid-19 patients mehdi pishgahi1, kimia karimi toudeshki1, saeed safari2,3∗, mahmoud yousefifard4 † 1. cardiology department, shahid beheshti university of medical sciences, tehran, iran. 2. proteomic research center, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. physiology research center, iran university of medical sciences, tehran, iran. received: january 2021; accepted: january 2021; published online: 24 february 2021 abstract: introduction: direct and indirect sequels of covid-19 in the cardiovascular system are unclear. the present study aims to investigate the echocardiography findings in covid-19 patients and possible correlations between the findings and the disease outcome. methods: in this cross-sectional study, baseline characteristics and echocardiographic findings of hospitalized covid-19 cases, and their correlation with mortality were evaluated. furthermore, computed tomography (ct) angiography was performed to assess possible pulmonary embolism. in-hospital mortality was considered as the main outcome of the present study. results: 680 confirmed covid19 cases with the mean age of 55.15 ± 10.92 (range: 28 – 79) years were studied (63.09% male). analysis showed that history of ischemic heart disease (rr=1.14; 95% ci: 1.08-1.19), history of hypertension (rr=1.04; 95% ci: 1.00-1.08), presence of embolism in main pulmonary artery (rr=1.53; 95% ci: 1.35-1.74), ct involvement more than 70% (rr=1.08; 95% ci: 1.1.01-1.16), left ventricular ejection fraction < 30 (rr=1.19; 95% ci: 1.07-1.32), pleural effusion (rr=1.08; 95% ci: 1.00-1.16), pulmonary artery systolic blood pressure 35 to 50 mmhg (rr=1.11; 95% ci: 1.03-1.18), right ventricular dysfunction (rr=1.54; 95% ci: 1.40-1.08), and collapsed inferior vena-cava (rr=1.05; 95% ci: 1.01-1.08) were independent prognostic factors of in-hospital mortality. conclusion: our study showed that cardiac involvement is a prevalent complication in covid-19 patients. echocardiography findings have independent prognostic value for prediction of in-hospital mortality. since echocardiography is an easy and accessible method, echocardiography monitoring of covid-19 patients can be used as a screening tool for identification of high-risk patients. keywords: electrocardiography; covid-19; sars-cov-2; outcome; mortality cite this article as: pishgahi m, karimi toudeshki k, safari s, yousefifard m. echocardiographic abnormalities as independent prognostic factors of in-hospital mortality among covid-19 patients. arch acad emerg med. 2021; 9(1): e21. 1. introduction the covid-19 pandemic has become a global challenge, and the number of those affected with the disease is increasing. initial reports indicated a 3 to 5% mortality rate among the patients having this respiratory infection. however, with the ∗corresponding author: saeed safari; emergency department, shohadaye tajrish hospital, tajrish square, tehran, iran. email: s.safari@sbmu.ac.ir; safari266@gmail.com; tel: +9822721155. † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; e-mail: yousefifard.m@iums.ac.ir. spread of the disease in different parts of the world, the mortality rate of the disease has risen. as of today, considering closed cases of the disease, the mortality rate among covid19 patients has been reported to be 21% (1). while the mentioned mortality rate for covid-19 is considerably high, there is no definitive cure for the disease, and all interventions performed for the patients are rather supportive (2, 3). current evidence suggests that the host tissue for severe acute respiratory syndrome coronavirus 2 (sars-cov2) is not only the lung, and since its receptor, angiotensin converting enzyme 2, is present in vascular tissue, kidneys, brain and cardiac tissue, symptoms other than respiratory involvements have been reported in covid-19 patients (4-6). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pishgahi et al. 2 a number of studies show that sars-cov-2 attacks cardiac and vascular tissues and blood vessels, causing various alterations and resulting events (4, 6), including thromboembolic accidents such as pulmonary embolism and stroke. clinical evaluations of the patients indicate that cardiac manifestations present in one of every five patients (7). these cardiac injuries can occur even without presenting symptoms of pneumonia (8). a meta-analysis on three articles showed that cardiac troponin i levels in patients with severe form of covid-19 are significantly higher compared to that of non-severe patients (9). hence, covid-19 seems to affect the heart directly. on the other hand, pulmonary involvement and increased pressure of pulmonary artery can cause right heart overload. also, vascular endothelium involvement in lungs increases the risk of stasis, followed by thrombosis, which may lead to right heart failure through increasing pulmonary artery pressure. as a result, considering the direct and indirect effects of covid-19 on heart, the present study aims to investigate the echocardiography findings in covid-19 patients and possible correlations between the findings and the disease outcome. 2. methods 2.1. study design and patients data of 680 confirmed covid-19 patients admitted to shohadaye tajrish and modarres educational hospitals, tehran, iran, from april to november 2020 were included, prospectively. covid-19 pneumonia was confirmed based on chest ct scan and rt-pcr. out-of-hospital mortality and pregnancy were exclusion criteria. before patient recruitment, ethical approval was obtained from ethic committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.retech.rec.1399.060). written informed consent was obtained and researchers adhered to principles of helsinki declaration. 2.2. data gathering and outcome during hospitalization, demographic and baseline characteristics were recorded. echocardiography was performed using sonosite set (edge l1, usa) and in standard position. all patients were assessed by an expert cardiologist with 10 years of clinical experience in echocardiography. all echocardiography abnormalities was assessed and reported. performing and interpretation of echocardiography was done according to american society of echocardiography guideline (10). the echocardiograms were ordered by in-charge physicians for intensive care unit (icu)-admitted patients, intubated patients, severely ill cases, patients with hemodynamic instability, and those with suspected concomitant cardiac problem with covid-19 pneumonia. in addition, pulmonary involvement on ct scan was assessed. furthermore, ct pulmonary angiogram was performed to assess possible pulmonary embolism (11). in-hospital mortality was considered as the main outcome of the present study. 2.3. statistical analysis all analyses were performed in stata 14.0. t-test and chisquared (or exact fisher) test were used to evaluate association of baseline and echocardiography findings with inhospital mortality. then, potential prognostic factors (factors with a p value less than 0.1 in univariate analyses) were entered into a backward (stepwise) regression model using general linear models. multivariate analysis was adjusted for age, comorbidity, percentage of ct involvement, and presence of thromboembolism in pulmonary vessels. significance level was considered as p <0.05. 3. results 680 confirmed covid-19 cases with the mean age of 55.15 ± 10.92 (range: 28 – 79) years were studied (63.09% male). hypertension (43.82%), diabetes mellitus (24.56%), and ischemic heart disease (16.47%) were among the most frequent underlying disease of this series, respectively. the rate of mortality was 8.38% in all hospitalized cases. ct scan involvement was less than 50%, 40-70%. and >70% in 62.94%, 28.09%, and 8.97% of patients, respectively. ct pulmonary angiogram was normal in 91.76% of the patients. 6.03% had segmental/sub segmental embolism and 2.21% had main pulmonary artery embolism. table 1 compares the baseline characteristics of covid-19 cases between survived and non-survived cases. there was a significant correlation between age (p=0.0006), history of ischemic heart diseases (p<0.0001), history of diabetes mellitus (p = 0.010), and hypertension (p=0.001) with higher rate of mortality. in addition, higher lung involvement in ct scan and presence of embolism in ct pulmonary angiogram correlated with patients’ mortality (p=0.0002). 3.1. echocardiographic findings table 2 summarizes the echocardiographic findings of covid-19 cases. left ventricular ejection fraction (ef) < 50% (22.94%), right ventricular dilation (18.53%), left ventricular dilation (7.06%), pleural effusion (6.03%), right ventricular clot (0.44%), moderate and moderate-severe tricuspid regurgitation (17.35%), pulmonary artery systolic pressure (pasp) of 35-50 mmhg (7.65%), pasp more than 50 mmhg (2.5%), and dilated (13.82%) and collapsed (45.59%) inferior vena cava (ivc) were the most important findings in echocardiography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e21 3.2. prognostic factors of death univariate logistic regression showed a significant association between covid-19 patients’ mortality and left ventricular ef (p=0.0001), left ventricular dilation (p<0.0001), pleural effusion (p<0.0001), right ventricular dilation (p<0.0001), right ventricular clot (p=0.020), tricuspid regurgitation (p<0.0001), pasp level (p=0.0001), and inferior vena cava size (p<0.0001). stepwise multiple regression showed that history of ischemic heart disease (rr=1.14; 95% ci: 1.08-1.19), history of hypertension (rr=1.04; 95% ci: 1.00-1.08), presence of embolism in main pulmonary artery (rr=1.53; 95% ci: 1.35-1.74), ct involvement more than 70% (rr=1.08; 95% ci: 1.1.01-1.16), left ventricular ejection fraction < 30 (rr=1.19; 95% ci: 1.071.32), pleural effusion (rr=1.08; 95% ci: 1.00-1.16), pasp 35 to 50 mmhg (rr=1.11; 95% ci: 1.03-1.18), right ventricular dysfunction (rr=1.54; 95% ci: 1.40-1.08), and collapsed ivc (rr=1.05; 95% ci: 1.01-1.08) were independent prognostic factors of in-hospital mortality (table 3). 4. discussion findings of the present study demonstrated that echocardiographic abnormalities in covid-19 patients are common, and among the abnormalities, history of ischemic heart disease, history of hypertension, ef<30%, pleural effusion, rv dysfunction, increased pasp and ivc collapse are independent prognostic factors of patients’ mortality. these factors can predict mortality independent from pulmonary involvement and presence of pulmonary embolism. cardiovascular complications and coagulopathies have been evaluated in different studies and have shown to be directly related to the mortality rate of patients (7, 9, 12). evidences observed in echocardiography, provided in the current study, are in line with previous researches. initially, the lung tissue was presumed to be the only target of sars-cov-2, but as time went on, other tissues were found to be hosting the virus as well. sars-cov-2 receptor, ace2, is expressed largely in blood vessel walls and heart (13). therefore, if the virus enters the blood stream, it can easily infect the mentioned tissues. hence, cardiovascular complications and coagulopathies have been evaluated in different studies and have shown to be directly related to the mortality rate of patients (7, 9, 12). evidences observed in echocardiography, provided in the current study are suggestive of the prior mentioned hypothesis. it has been thus far shown that covid-19 could cause a hypercoagulable state in the body throughout the course of viral infection, through causing alterations in coagulation factors or changes in homeostasis (14-16). thrombosis lead to many problems, including pulmonary embolism and cardiac muscle injury. moreover, covid-19-associated pneumonia has been shown to be a risk factor for pulmonary embolism (17). considering the mentioned evidence, there seems to be an undeniable relationship between covid19, thrombosis and pte, and the results of this study are in line with these findings. therefore, it is of great importance to closely monitor covid-19 patients admitted to hospital for possible incidence of thrombosis, and even start prophylactic anticoagulant therapy (18) . however, in multivariate analysis, echocardiographic abnormalities independently predicted in-hospital mortality of covid-19 patients after adjusting the analysis for ct angiography findings. this suggests that in addition to the effects of covid-19 on blood vessels and the increased odds of thrombosis, its direct effects on the cardiac muscle also is associated with poor prognosis of patients. rv dilatation and dysfunction, lv dysfunction and subsequent reduced ef were the echocardiography manifestations implicating heart muscle weakness and injury during the acute state of disease in this study. to be illustrated, viral infections can contribute to a complication, known as viral cardiomyopathy, which is one of the primary reasons of cardiac dilation (19); and coronaviruses are known to be one of the major viral causes of cardiomyopathy (20). this study, in line with the results of other studies, suggests that the presence of right and left heart dysfunction in a hospitalized covid-19 patient’s echocardiogram, could be an independent predictor of death. in the early studies on covid-19, age was considered to be a risk factor for mortality in patients (21, 22). however, age seems to be the prerequisite of changes in different tissues, rather than being an independent factor. while aging, an individual becomes more prone to cardiovascular disorders (23), and in case of sars-cov-2 infection, severe symptoms of the disease and cardiovascular manifestations are more likely to happen. in the present study, age was not independently correlated with mortality, as observed in multivariate analysis, but it may affect the patients as a dependent factor. seemingly, various tissue changes in the elderly people cause serious complications following covid-19 infection. results of the present study suggest that respiratory and cardiovascular monitoring should be performed for covid19 patients, as early as possible; some of the patients may have underlying cardiovascular disorders without showing any significant respiratory symptoms (8). accordingly, in addition to pulmonary ct scans, cardiovascular evaluations are recommended in the process of patient care. this matter is of utmost importance when patients have a positive history for cardiovascular disorders. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pishgahi et al. 4 5. limitations several limitations are present in the current study. in this study, echocardiography assessments were performed on different days of hospital admission for different patients, and were carried out only when the patient’s status had worsened. anyhow, the present study is a preliminary study, aiming to provide evidences of cardiovascular involvement in covid-19 patients. in addition, measurement of rv dilatation is very difficult in icu patients, lying on their back. moreover, the effect of ventilation on rv dilatation is another factor that could influence the validity of findings. therefore, more clinical and laboratory factors should be taken into account in future studies. 6. conclusion our study showed that cardiac involvement is a prevalent complication among covid-19 patients. in addition, echocardiography findings are independent prognostic factors in prediction of in-hospital mortality. since echocardiography is an easy and accessible method, echocardiography monitoring of covid-19 patients can be used as a screening tool for detection of high-risk patients. 7. declarations 7.1. acknowledgement the personnel of cardiology departments of shohadaye tajrish and modarres hospitals, who helped us in management of these patients, are thanked and appreciated. 7.2. author contribution study design and data gathering: mp, ss, my analysis: ss and my interpreting the results: all authors. drafting: my and ss critically revised: all authors all authors read and approved the final version of the paper to be submitted. 7.3. conflict of interest none. 7.4. funding this study was support by vice chancellor of research and technology, shahid beheshti university of medical sciences (grant number: 23317). references 1. world metrics. covid-19 coronavirus outbreak: world metrics; [available from: https://www.worldometers.info/coronavirus/. 2. ai t, yang z, hou h, zhan c, chen c, lv w, et al. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases. radiology. 2020:200642. 3. razzaghi a, soori h, abadi a, khosravi a. world health organization’s estimates of death related to road traffic crashes and their discrepancy with other countries’ national report. journal of injury & violence research. 2020;12(3). 4. wu c, hu x, song j, du c, xu j, yang d, et al. heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (covid-19). medrxiv. 2020. 5. wang t, du z, zhu f, cao z, an y, gao y, et al. comorbidities and multi-organ injuries in the treatment of covid19. the lancet. 2020. 6. zheng y-y, ma y-t, zhang j-y, xie x. covid-19 and the cardiovascular system. nature reviews cardiology. 2020:1-2. 7. shi s, qin m, shen b, cai y, liu t, yang f, et al. association of cardiac injury with mortality in hospitalized patients with covid-19 in wuhan, china. jama cardiology. 2020. 8. inciardi rm, lupi l, zaccone g, italia l, raffo m, tomasoni d, et al. cardiac involvement in a patient with coronavirus disease 2019 (covid-19). jama cardiology. 2020. 9. lippi g, lavie cj, sanchis-gomar f. cardiac troponin i in patients with coronavirus disease 2019 (covid19): evidence from a meta-analysis. prog cardiovasc dis. 2020:s0033-620(20)30055-4. 10. pellikka pa, arruda-olson a, chaudhry fa, chen mh, marshall je, porter tr, et al. guidelines for performance, interpretation, and application of stress echocardiography in ischemic heart disease: from the american society of echocardiography. journal of the american society of echocardiography. 2020;33(1):1-41. e8. 11. moore aje, wachsmann j, chamarthy mr, panjikaran l, tanabe y, rajiah p. imaging of acute pulmonary embolism: an update. cardiovasc diagn ther. 2018;8(3):225-43. 12. klok fa, kruip mjha, van der meer njm, arbous ms, gommers dampj, kant km, et al. incidence of thrombotic complications in critically ill icu patients with covid-19. thrombosis research. 2020. 13. south am, diz d, chappell mc. covid-19, ace2 and the cardiovascular consequences. american physiological society rockville, md; 2020. 14. connors jm, levy jh. thromboinflammation and the hypercoagulability of covid-19. journal of thrombosis and haemostasis. 2020;18(7):1559-61. 15. panigada m, bottino n, tagliabue p, grasselli g, novembrino c, chantarangkul v, et al. hypercoagulability of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e21 covid-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. journal of thrombosis and haemostasis. 2020;18(7):1738-42. 16. singhania n, bansal s, nimmatoori dp, ejaz aa, mccullough pa, singhania g. current overview on hypercoagulability in covid-19. american journal of cardiovascular drugs. 2020;20(5):393-403. 17. grillet f, behr j, calame p, aubry s, delabrousse e. acute pulmonary embolism associated with covid-19 pneumonia detected with pulmonary ct angiography. radiology. 2020;296(3):e186-e8. 18. sakr y, giovini m, leone m, pizzilli g, kortgen a, bauer m, et al. pulmonary embolism in patients with coronavirus disease-2019 (covid-19) pneumonia: a narrative review. annals of intensive care. 2020;10(1):1-13. 19. schultz jc, hilliard aa, cooper lt, jr., rihal cs. diagnosis and treatment of viral myocarditis. mayo clin proc. 2009;84(11):1001-9. 20. kearney mt, cotton jm, richardson pj, shah am. viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management. postgraduate medical journal. 2001;77(903):4-10. 21. novel cpere. the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid-19) in china. zhonghua liu xing bing xue za zhi= zhonghua liuxingbingxue zazhi. 2020;41(2):145. 22. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet. 2020. 23. dhingra r, vasan rs. age as a risk factor. the medical clinics of north america. 2012;96(1):87-91. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pishgahi et al. 6 table 1: baseline characteristics of included covid-19 patients variable survived (n=623) died (n=57) total (n=680) p value age (year; mean and sd) 54.72±10.88 59.88±10.32 55.15±10.92 0.0006 28-39 54 (8.67) 1 (1.75) 55 (8.09) 40-49 173 (27.77) 11 (19.3) 184 (27.06) 50-59 153 (24.56) 19 (33.33) 172 (25.29) 60-69 185 (29.7) 13 (22.81) 198 (29.12) 70-79 58 (9.31) 13 (22.81) 71 (10.44) gender male 392 (62.92) 37 (64.91) 429 (63.09) 0.766 female 231 (37.08) 20 (35.09) 251 (36.91) comorbidity ischemic heart disease no 538 (86.36) 30 (52.63) 568 (83.53) <0.0001 yes 85 (13.64) 27 (47.37) 112 (16.47) diabetes mellitus no 478 (76.73) 35 (61.4) 513 (75.44) 0.010 yes 145 (23.27) 22 (38.6) 167 (24.56) hypertension no 362 (58.11) 20 (35.09) 382 (56.18) 0.001 yes 261 (41.89) 37 (64.91) 298 (43.82) ct involvement (%) <50 409 (65.65) 19 (33.33) 428 (62.94) 0.0001* 50-70 172 (27.61) 19 (33.33) 191 (28.09) >70 42 (6.74) 19 (33.33) 61 (8.97) ct pulmonary angiogram no embolism 584 (93.74) 40 (70.18) 624 (91.76) 0.0001* segmental/sub segment embolism 35 (5.62) 6 (10.53) 41 (6.03) main pulmonary artery embolism 4 (0.64) 11 (19.3) 15 (2.21) duration of hospitalization (day) 7.42±2.62 8.79±2.89 7.53±2.67 0.0002 data are presented as mean ± standard deviation or frequency (%). ct: computed tomography; sd: standard deviation; *based on kruskal–wallis test. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e21 table 2: echocardiography findings in covid-19 patients based on in-hospital mortality variable survived (n=623) died (n=57) total (n=680) p value left ventricular ef (%) >50 501 (80.42) 23 (40.35) 524 (77.06) 0.0001* 40-50 69 (11.08) 19 (33.33) 88 (12.94) 30-40 40 (6.42) 7 (12.28) 47 (6.91) <30 13 (2.09) 8 (14.04) 21 (3.09) left ventricular dilation no 586 (94.06) 46 (80.7) 632 (92.94) <0.0001 yes 37 (5.94) 11 (19.3) 48 (7.06) pleural effusion no 592 (95.02) 47 (82.46) 639 (93.97) <0.0001 yes 31 (4.98) 10 (17.54) 41 (6.03) right ventricular dilation no 535 (85.87) 19 (33.33) 554 (81.47) <0.0001 yes 88 (14.13) 38 (66.67) 126 (18.53) right ventricular clot no 622 (99.84) 55 (96.49) 677 (99.56) 0.020 yes 1 (0.16) 2 (3.51) 3 (0.44) tricuspid regurgitation no 542 (87.00) 20 (35.09) 562 (82.65) <0.0001 yes 81 (13.00) 37 (64.91) 118 (17.35) pasp <35 572 (91.81) 39 (68.42) 611 (89.85) 0.0001 35-50 37 (5.94) 15 (26.32) 52 (7.65) >50 14 (2.25) 3 (5.26) 17 (2.5) ivc size normal 261 (41.89) 15 (26.32) 276 (40.59) <0.0001 dilated 73 (11.72) 21 (36.84) 94 (13.82) collapsed 289 (46.39) 21 (36.84) 310 (45.59) data are presented as frequency (%); *based on kruskal–wallis test; ivc: inferior vena cava; pasp: pulmonary arterial systolic pressure; ef: ejection fraction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pishgahi et al. 8 table 3: multivariate regression for identifying independent prognostic factors of covid-19-related mortality variable rr 95% ci p value history of ischemic heart diseases no ref. ref. yes 1.14 1.08 1.19 <0.0001 history of hypertension no ref. ref. yes 1.04 1.00 1.08 0.031 ct pulmonary angiogram no emboli ref. ref. main pulmonary arteries emboli 1.53 1.35 1.74 <0.0001 ct involvement (%) <50 ref. ref. >70 1.08 1.01 1.16 0.023 left ventricular ef (%) >50 ref. ref. <30 1.19 1.07 1.32 <0.0001 pleural effusion no ref. ref. yes 1.08 1.00 1.16 0.044 pasp (mmhg) <30 ref. ref. 35-50 1.11 1.03 1.18 <0.0001 right ventricular dysfunction no ref. ref. yes 1.54 1.40 1.70 <0.0001 ivc size normal ref. ref. collapsed 1.05 1.01 1.08 0.015 ci: confidence interval; ef: ejection fraction; ivc: inferior vena cava; pasp: pulmonary arterial systolic pressure; rr: relative risk; ct: computed tomography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e48 or i g i n a l re s e a rc h the role of cardiac arrest sonographic exam (case) in predicting the outcome of cardiopulmonary resuscitation; a cross-sectional study babak masoumi1, reza azizkhani1, farhad heydari1∗, majid zamani1, mehdi nasr isfahani1 1. department of emergency medicine, faculty of medicine, isfahan university of medical sciences, isfahan, iran. received: april 2021; accepted: may 2021; published online: 28 june 2021 abstract: introduction: ultrasonography (us) has been suggested as an integral part of resuscitation to identify potentially reversible causes of cardiac arrest (ca). this study aimed to evaluate the association between cardiac activity on ultrasonography during resuscitation and outcome of patients with non-shockable rhythms. methods: we conducted a prospective, observational study on adult patients presenting with ca or experiencing ca in the emergency department (ed), and initial non-shockable rhythm. us examination of the sub-xiphoid region was performed during the 10-second interval of rhythm and pulse check and the association of us findings and patients’ outcomes was evaluated. results: 151 patients with the mean age of 65.32 ± 11.68 years were evaluated (76.2% male). 43 patients (28.5%) demonstrated cardiac activity on the initial us. the rate of asystole in initial rhythm was 58.9% (n=89). return of spontaneous circulation (rosc) was achieved in 36 (23.8%) patients, twenty (13.2%) survived to hospital admission and seven (4.6%) survived to hospital discharge. when the cardiac standstill duration increased to six minutes, no patient survived hospital discharge. potentially reversible causes were detected in 15 cases (9.9%), and four of them survived to hospital discharge. cardiac activity on first scan was associated with rosc (or: 6.86, 95%ci: 2.92-16.09; p < 0.001), survival to hospital admission (or: 17.80, 95%ci: 3.95–80.17; p < 0.001), and survival to hospital discharge (or: 17.35, 95%ci: 2.02–148.92; p = 0.001). conclusion: in non-traumatic cardiac arrest patients with non-shockable rhythms, bedside us is of great importance in predicting rosc. the presence of pulseless electrical activity (pea) rhythm and cardiac activity on initial us were associated with rosc, survival to hospital admission, and hospital discharge. when the cardiac standstill duration increased to six minutes, no patient survived hospital discharge. keywords: heart arrest; cardiopulmonary resuscitation; return of spontaneous circulation; ultrasonography cite this article as: masoumi b, azizkhani r, heydari f, zamani m, nasr isfahani m. the role of cardiac arrest sonographic exam (case) in predicting the outcome of cardiopulmonary resuscitation; a cross-sectional study. arch acad emerg med. 2021; 9(1): e48. https://doi.org/10.22037/aaem.v9i1.1272. 1. introduction patients with cardiac arrest (ca) should be treated using algorithm-based methods such as basic life support (bls) and advanced life support (als). ca with non-shockable rhythms continues to have poor outcomes (1). compared to those with a shockable rhythm, patients with pulseless electrical activity (pea) have poorer prognosis (survival rate: 40% vs 6%, respectively) (2). pea can be sub-divided into electromechanical dissociation (emd) (true-pea) and pseudo∗corresponding author: farhad heydari; department of emergency medicine, alzahra hospital, sofeh ave., keshvari blvd., isfahan, iran. tel: +989131367643, email: farhad_heidari@med.mui.ac.ir, orcid: https://orcid.org/0000-0002-6296-0045. emd (pseudo-pea) based on the absence or presence of cardiac activity. the survival rate of pseudo-pea has been reported to be significantly higher than that of true-pea, while therapeutic strategies in both cases are similar (3). rapid identification and correction of potentially reversible causes of cardiac arrest in patients with a non-shockable rhythm is an important step for their management (4). ultrasonography (us) has been suggested as an integral part of resuscitation to identify potentially reversible causes of ca, such as pericardial tamponade, pulmonary embolism (pe), tension pneumothorax, and hypovolemia (3-5). additionally, the us may differentiate between false and true pea, based on the presence or absence of organized cardiac motion. detection of cardiac motion on ultrasound may be an early sign of return of spontaneous circulation (rosc), and is this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. masoumi et al. 2 a good predictor of survival (5-7). using ultrasonography it is possible to differentiate between true asystole and fine ventricular fibrillation, especially when rhythm monitoring is in doubt (e.g., artifacts), with both prognostic and therapeutic implications (8). while us has been suggested in ca, there has been no protocol to explore exactly how ultrasound should be integrated with als. furthermore, the main point is that ultrasound does not interfere with the chest compressions. thus, us is safely integrated into the als when it is performed in 10s intervals for rhythm assessment and checking carotid pulse (58). however, studies have shown that experienced providers may be able to perform us in less than 10s. a few studies have evaluated the association between us during cardiopulmonary resuscitation (cpr) pauses and interruptions in cpr in the emergency department (ed) (9-11). a systematic review showed that survival to admission rate in patients without cardiac activity on ultrasound termed cardiac standstill was 2.4% (12). therefore, the chances of survival associated with cardiac standstill are very low (5). in this study, we evaluated the association between the cardiac activity on ultrasound during resuscitation and outcome of patients with pulseless electrical activity (pea) or asystole. 2. methods 2.1. study design and setting this prospective, observational study was conducted from march 2018 to may 2019 in two urban emergency departments (ed) with an emergency medicine residency program (al-zahra and kashani hospitals, isfahan, iran). the study protocol conformed to the principles of the declaration of helsinki, and ethics approval was obtained from the ethics committee of isfahan university of medical sciences (ir.mui.rec.1396.2.070). 2.2. participants all non-traumatic patients aged at least 18 years presenting to the ed with cardiac arrest (ca) or experiencing ca in the ed, and initial rhythm of asystole or pea were eligible. patients with rosc before ed arrival, brief resuscitation efforts lasting less than four minutes, or failure to undergo us during resuscitation were excluded. 2.3. study protocol patients with cardiac arrest were evaluated and managed per als guidelines. our research protocol was a three-step ultrasound (us) protocol that evaluated cardiac activity and reversible causes of ca in non-shockable rhythms. at the beginning of als, during the first cpr pauses, the sonographer evaluated and recorded the cardiac activity. during the second pauses, the cardiac activity and pericardial effusion were evaluated and recorded and, if pericardial effusion presented, signs of tamponade such as early diastolic right ventricular collapse were assessed. in the third pauses, cardiac activity and the presence of pulmonary embolism (right ventricular enlargement with left ventricular collapse) were checked and recorded. during cpr, hypovolemia (inferior vena cava [ivc] diameter measurement by us) and tension pneumothorax were evaluated on a case-by-case basis (figure1). cardiac activity was defined as any visible atrial, valvular, or ventricular movement, excluding movement of blood within the cardiac chambers or isolated valve movement. treating clinicians were not blinded to the us findings except for the presence or absence of cardiac motion. all ultrasounds were performed in less than 10 seconds during pauses in resuscitation to determine the cardiac rhythm and pulse checks. to obtain ultrasonic images, cpr did not stop. to avoid any interruption with cpr, the treating emergency physician notified the sonographer 5 seconds before the pulse checks to prepare for a 10-second pause by positioning the ultrasound probe in the sub-xiphoid region to take the four-chamber view of the heart. ultrasound images were obtained using a sub-xiphoid (subcostal) view (5, 11, 13). ultrasound was implemented by the five emergency medicine specialists who had more than 6 years’ experience in emergency echocardiography. us service was provided 24 hours a day, 7 days a week. an ultrasonography device (philips affiniti 70) with a curved probe (2–6 mhz) was used in this study. 2.4. data gathering standard forms were used to record patients’ age, gender, out-of-hospital or in-hospital arrest, initial rhythms in the ed, ultrasound findings, resuscitation outcome (rosc, survival to hospital admission, survival to hospital discharge, and death), and the duration of cpr. 2.5. statistical analysis all analyses were performed using spss 22.0 for windows (spss inc., chicago, illinois, usa). categorical data were reported in frequency and percentages, while continuous data were reported as mean (standard deviation [sd]) or proportion with 95% confidence interval (95% ci). baseline differences were evaluated via fisher’s exact and student t-test analyses, and the chi-square test was used to identify differences between groups of nominal variables. binary logistic regression was first performed to obtain odds ratio estimates with 95% confidence intervals (ci) with p values for the three outcomes of 1) rosc, 2) survival to hospital admission, and 3) survival to hospital discharge. interaction between independent variables was assessed in a pairwise fashion for all variables. test characteristics of sensitivity and specificity, positive and negative predictive values, and accuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e48 racy of cardiac standstill for the three outcomes were calculated with 95% ci. statistical significance was set at p <0.05. 3. results 3.1. baseline characteristics of studied cases a total of 175 patients were enrolled from march 2018 to may 2019; of which, 151 patients were included in the study and underwent us assessment during cardiac arrest management in the ed (figure 2). overall, 43 patients (28.5%) demonstrated cardiac activity on the initial us in the ed. the mean age of the patients was 65.32 ± 11.68 (35–92) years, and 115 (76.2%) were male. the rate of asystole in initial rhythm was 58.9% (n=89), and the rate of the out-of-hospital cardiac arrest (ohca) was 84.8% (n = 128). table 1 compares the baseline characteristics between cases with rosc and others. rosc was achieved in 36 out of 151 (23.8%) patients, twenty patients (13.2%) survived to hospital admission and seven patients (4.6%) survived to hospital discharge. also, pericardial effusion without tamponade was detected in six patients and right ventricular dilatation in four patients. one of these patients received thrombolytic therapy and survived to hospital discharge. hypovolemia was detected in five cases. when appropriate management was applied promptly, nine patients were successfully resuscitated (rosc), and four of them survived to hospital discharge. the rate of rosc in in-hospital cardiac arrest (ihca) and ohca was 10 (43.5%) and 26 (20.3%) (p=0.03). survival to hospital admission was higher for ihca (30.4% vs 10.2%, p = 0.02) but survival to hospital discharge between ihca and ohca was not different (8.7% vs 4.1%, p = 0.29). the success rate of resuscitation (rosc) of patients with pea and asystole rhythm was 43.5% (27 cases) and 10.1% (9 cases), respectively (p<0.001). among the 36 patients that had cardiac activity at first glance, 24 cases (66.7 %) achieved rosc and in 115 patients without cardiac activity, 19 cases (16.5%) achieved rosc (p<0.001). among the 94 patients in whom no cardiac activity was detected on all scans, only 3 (8.3%) had rosc and in the other 91 cases (79.1%) the efforts for resuscitation were not successful. none of them survived hospital discharge. neither age nor gender was a significant predictor of rosc (table 1). 3.2. us findings the percentage of patients with cardiac activity on initial us differed between asystole and pea patients (11.2% vs 53.2%, p<0.001). twenty-nine cases (46.8%) presenting with pea had no cardiac activity on initial us (true emd). on the other hand, 33 cases (53.2%) had cardiac activity (pseudo-emd). the rates of rosc were 63.6% for those in pseudo-emd and 20.7% for those in true emd. so in patients with pea rhythm, the presence of cardiac activity during the resuscitation was significantly associated with rosc (p=0.001). six out of 62 patients (9.7%) presenting with pea had rosc and survived to hospital discharge. only one out of 89 cases (1.1%) with asystole as initial rhythm survived to hospital discharge (p=0.02). the presence of cardiac activity on the first ultrasonography was significantly associated with survival to hospital admission and hospital discharge (table 2). among 43 patients with cardiac activity on initial us, six cases (14.0%) survived to hospital discharge, whereas only one out of the 108 (1.0%) patients without cardiac activity on initial us survived to hospital discharge (p = 0.002). the binary logistic regression analysis identified variables that were associated with rosc (table 2). cardiac activity on first scan was associated with rosc (or: 6.86, 95%ci: 2.92-16.09), survival to hospital admission (or: 17.80, 95%ci: 3.95–80.17), and survival to hospital discharge (or: 17.35, 95%ci: 2.02–148.92) (table 3). 3.3. screening performance characteristics of us in cpr the diagnostic performance of us (lack of cardiac activity) for no rosc, non-survival to hospital admission, and discharge are shown in table 5. the absence of cardiac activity on us showed a sensitivity and positive predictive value (ppv ) of 74.3% (95% ci: 66.4–81.2%) and 99.1% (95% ci: 94.6–99.8%) for non-survival to hospital discharge. none of patients with asystole rhythm and lack of cardiac activity in us survived to hospital discharge (table 4). 4. discussion point-of-care ultrasound (pocus) and echocardiography have been suggested for the detection of reversible causes of cardiac arrest during resuscitation in the 2020 update of advanced cardiovascular life support (acls) guidelines, and to assist in the identification of rosc (13, 14). in our study, we successfully performed a bedside sonography protocol in keeping with an acceptable 10-second pause for pulse checks during cpr. it is crucial to identify and treat all potential secondary causes of asystole or pea as rapidly as possible. potentially reversible causes of hypovolemia, massive pe, and pericardial effusion were detected in 15 cases (9.9%), and four of them survived hospital discharge (2.6%). the rate of reversible causes in our study was low; however, the rate of survival to hospital discharge in these patients was higher than the whole study population (26.7% vs 4.6%,), and this shows the importance of finding reversible causes and promptly treat them to increase patient’s chances of survival. consistent with our results, gaspari et al. have demonstrated that pea with a reversible cause has a higher survival rate to discharge (15.4%) than pea without a reversible cause (1.3%) (5). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. masoumi et al. 4 our study on adult patients with non-traumatic cardiac arrest with non-shockable rhythms indicated that the presence of pea rhythm and cardiac activity on initial us were associated with rosc, survival to hospital admission, and hospital discharge. the rate of rosc was 23.8% in all patients and for those with and without cardiac activity the rates were 66.7% and 16.5%, respectively. rate of rosc in previous studies on cardiac arrest patients with cardiac activity range from 24% to 73% (5). the rate of survival to hospital admission and hospital discharge in patients with cardiac activity was 37.2% and 14.0%, respectively; which is higher than the rate obtained in previous studies (5, 15). the reason for the increase in survival rate can be the treatment of reversible causes found by ultrasound, as well as more efforts to resuscitate patients with cardiac motion and longer cpr of these patients. the overall survival rate to hospital discharge in the present study (4.6%) was comparable to previous studies (5, 15). our findings are similar to previous studies that have shown the association of the presence of cardiac activity on initial cardiac us with successful rosc and survival (5, 6, 15-17). one out of the 108 (1.0%) patients without cardiac activity on initial us survived hospital discharge. rates of survival to hospital discharge in previous studies in patients without cardiac activity on initial us range from 0% to 10% (18). chardoli et al. reported that, regardless of the initial rhythm of patients, all of those who did not show cardiac activity in the initial us died (1). one of the studies with the highest survival rates in patients without cardiac activity showed that out of 50 patients without cardiac activity, 5 (10%) survived (3). in another study, of the 530 patients without cardiac activity on initial us, only 3 patients (0.6%) survived hospital discharge (5). a previous meta-analysis and systematic review snapshot reported that the absence of cardiac activity in the us should not be used alone to predict failure of rosc, with survival to admission rate of 2.4% in patients with cardiac standstill (12). other studies have reached similar conclusions about the poor prognosis following cardiac arrest associated with the absence of cardiac activity in us (4, 6). among 94 patients in whom no cardiac activity was detected on any of the scans, only 3 (8.3%) had rosc and in the other 91 cases (79.1%) the efforts for resuscitation were not successful. in other words, when the cardiac standstill duration increased to six minutes, no patient lived to hospital discharge. thus, a cardiac standstill on the serial us may predict non-survival. the us is a useful tool for determining pseudo-pea. studies show that 42% to 86% of the total pea patients are pseudopea (19). out of the 62 patients with pea, 33 (53.2%) had cardiac activity on initial us (pseudo-emd). 63.6% of the patients with pseudo-pea achieved rosc and there were also higher rates of survival to discharge (15.2%). chardoli et al. found that 43% of the patients with pseudo-pea achieved rosc, whereas no patients with true pea achieved rosc (1). flato et al. showed that 70% of the patients with pseudo-pea achieved rosc and 20% of those with true pea and none of the patients with true pea survived hospital discharge (20). cardiac activity in the us had odd ratios of 6.86 for rosc, 17.80 for survival to hospital admission, and 17.35 for survival to hospital discharge. lalande et al. reported that cardiac activity in us, compared to its absence, had odd ratios of 16.9 for rosc, 10.3 for hospital admission, and 8.03 for hospital discharge (21). the absence of cardiac activity on us showed a sensitivity of 83.5%, specificity of 66.7%, negative predictive value (npv ) of 55.8%, and ppv of 88.9% for non-rosc, regardless of the initial rhythm they presented with. in asystole, the ppv of cardiac standstill on us for predicting non-survival to hospital discharge was 100% compared with 96.6% in pea. in a meta-analysis, ten studies with 1486 participants were included. presence of cardiac activity on us had a pooled sensitivity of 60.3% (95% ci 38.1–78.9%) and specificity of 91.5% (80.8–96.5%) for rosc (21). in another study by bolvardi et al., they found that us had a sensitivity of 73.2%, specificity of 92.2%, npv of 84.6%, and ppv of 83.7%. however, the inclusion criteria for patients were different in that study (6). in another study by beckett et al., as a predictor of failure to achieve rosc, us had a sensitivity of 96.2% and a specificity of 34.0% (22). 5. limitations the study sample size was relatively small. the most prominent limitation of this study, however, was potentially increased risk of bias with regard to lack of blinding for us results, and that patients with cardiac activity showed longer resuscitation times. the next limitation, presumably, is that the protocol used in this study has not been compared with other protocols. 6. conclusion in non-traumatic cardiac arrest patients with non-shockable rhythms, bedside us is of great importance in predicting rosc. the presence of pea rhythm and cardiac activity on initial us were associated with rosc, survival to hospital admission, and hospital discharge. when the cardiac standstill duration increased to six minutes, no patient survived hospital discharge. so, the absence of cardiac activity on serial us could imply that prolonged resuscitation may not provide measurable benefit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e48 7. declarations 7.1. acknowledgments the authors appreciate the insightful cooperation of the staff of the emergency departments of al-zahra hospital and kashani hospital, isfahan, iran. 7.2. funding and support this research was performed with the support of isfahan university of medical sciences. 7.3. author contribution surgical and medical practices and concept: b.m., f.h., m.z., r.a., m.n.i., design: b.m., f.h., r.a., data collection or processing: b.m., f.h., m.z., r.a., m.n.i., analysis or interpretation: f.h., b.m., literature search and writing: b.m., f.h., m.z., r.a., m.n.i., all authors approved the final version. 7.4. conflict of interest the authors declare no conflict of interests. references 1. chardoli m, heidari f, shuang-ming s, rabiee h, sharifalhoseini m, rahimi-movaghar v, et al. echocardiography integrated acls protocol versus conventional cardiopulmonary resuscitation in patients with pulseless electrical activity cardiac arrest. chinese journal of traumatology. 2012;15(5):284-7. 2. chan ps, mcnally b, tang f, kellermann a. recent 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ultrasound in cardiac standstill: a clinical review. the ultrasound journal. 2019;11(1):1-8. 19. rabjohns j, quan t, boniface k, pourmand a. pseudopulseless electrical activity in the emergency department, an evidence based approach. the american journal of emergency medicine. 2020;38(2):371-5. 20. flato uap, paiva ef, carballo mt, buehler am, marco r, timerman a. echocardiography for prognostication during the resuscitation of intensive care unit patients with non-shockable rhythm cardiac arrest. resuscitation. 2015;92:1-6. 21. lalande e, burwash-brennan t, burns k, atkinson p, lambert m, jarman b, et al. is point-of-care ultrasound a reliable predictor of outcome during atraumatic, non-shockable cardiac arrest? a systematic review and meta-analysis from the shoc investigators. resuscitation. 2019;139:159-66. 22. beckett n, atkinson p, fraser j, banerjee a, french j, talbot j-a, et al. do combined ultrasound and electrocardiogram-rhythm findings predict survival in emergency department cardiac arrest patients? the second sonography in hypotension and cardiac arrest in the emergency department (shoc-ed2) study. cjem. 2019;21(6):739-43. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e48 table 1: comparison of baseline characteristics and us findings between patients with return of spontaneous circulation (rosc) and others variables all (n=151) rosc (n = 36) non-rosc (n = 115) p value age (year) mean ± sd 65.32 ± 11.68 63.53 ± 12.59 65.89 ± 11.38 0.292 gender male 115 (76.2) 29 (25.2) 86 (74.8) 0.654 female 36 (23.8) 7 (19.4) 29 (80.6) initial rhythm asystole 89 (58.9) 9 (10.1) 80 (89.9) <0.001 pea 62 (41.1) 27 (43.5) 35 (56.5) arrest location ohca 128 (84.8) 26 (20.2) 102 (79.8) 0.030 ihca 23 (15.2) 10 (43.5) 13 (56.5) us findings cardiac activity on first scan 43 (28.5) 24 (66.7) 19 (16.5) <0.001 cardiac activity on any scan 57 (37.7) 33 (91.7) 24 (20.9) <0.001 cardiac activity on all scans 11 (7.3) 10 (27.8) 1 (0.01) <0.001 cardiac standstill on all scans 94 (62.3) 3 (8.3) 91 (79.1) <0.001 data are presented as mean ± standard deviation (sd) or frequency (%). ihca: in hospital cardiac arrest, ohca: out-of-hospital cardiac arrest, pea: pulseless electrical activity, us: ultrasonography. table 2: comparing the studied outcomes between patients with and without cardiac activity on ultrasonography (us) during cardiopulmonary resuscitation (cpr) outcomes cardiac activity on us p value with (n=43) without (n=108) rosc in ed 22 (51.2) 14 (13.0) <0.001 survival to hospital admission 15 (34.9) 5 (4.6) <0.001 survival to hospital discharge 6 (14.0) 1 (1.0) 0.002 data are presented as number (%). ed: emergency department, rosc: return of spontaneous circulation. table 3: predictors of outcomes in studied patients with cardiopulmonary arrest predictors odds ratio* (95% ci) p value return of spontaneous circulation (rosc) initial rhythm (pea) 7.034 3.097-15.975 <0.001 initial cardiac activity (yes) 6.857 2.923-16.085 <0.001 admission status (ihca) 3.018 1.191-7.649 0.020 survival to hospital admission initial rhythm (pea) 11.036 3.692-32.986 <0.001 initial cardiac activity (yes) 17.795 3.950-80.169 <0.001 admission status (ihca) 3.870 1.345-11.140 0.017 survival to hospital discharge initial rhythm (pea) 9.429 1.106-80.407 0.040 initial cardiac activity (yes) 17.351 2.022-148.922 0.001 admission status (ihca) 2.343 0.426-12.874 0.356 ihca: in hospital cardiac arrest, pea: pulseless electrical activity, ci: confidence interval. *odds ratios were calculated using binary logistic regression analysis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. masoumi et al. 8 table 4: screening performance characteristics of ultrasonography during cardiopulmonary resuscitation for predicting the return of spontaneous circulation (rosc), survival to hospital admission, and survival to hospital discharge characters rosc hospital admission hospital discharge overall sensitivity 83.5 (75.4-89.8) 59.1 (43.2-73.7) 74.3 (66.4-81.2) specificity 66.7 (49.0-81.4) 83.3 (58.6-96.4) 85.7 (42.1-99.6) ppv 88.9 (83.3-92.7) 89.7 (75.0-96.1) 99.1 (94.6-99.8) npv 55.8 (44.1-66.9) 45.5 (35.6-55.7) 95.4 (90.7-98.1) accuracy 79.5 (72.1-85.6) 66.1 (53.0-77.7) 74.8 (67.1-81.5) pulseless electrical activity sensitivity 65.7 (47.8-80.9) 59.1 (43.2-73.7) 50.0 (36.3-63.7) specificity 77.8 (57.7-91.4) 83.3 (58.6-96.4) 83.3 (35.9-99.6) ppv 79.3 (65.5-89.0) 89.7 (75.0-96.1) 96.6 (82.1-99.4) npv 63.6 (51.5-74.3) 45.5 (35.6-55.7) 15.2 (10.3-21.8) accuracy 71.0 (58.1-81.8) 66.1 (53.0-77.7) 53.2 (40.1-66.0) asystole sensitivity 91.2 (82.8-96.4) 89.7 (81.3-95.2) 89.8(81.5-95.2) specificity 33.3 (7.5-70.1) 50.0 (1.3-98.7) 100 ppv 92.4 (88.4-95.1) 98.7 (95.1-99.7) 100 npv 30.0 (11.8-57.8) 10.0 (2.4-33.6) 0.1(0.1-0.2) accuracy 85.4 (76.3-92.0) 88.8 (80.3-94.5) 89.9(81.7-95.3) data are presented with 95% confidence interval. ppv: positive predictive value, npv: negative predictive value. figure 1: cardiac arrest sonographic exam (case) schematic. als: advanced life support. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e48 figure 2: patients’ flow diagram and outcome. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e65 or i g i n a l re s e a rc h effect of underlying cardiovascular disease on the prognosis of covid-19 patients; a sex and age-dependent analysis mohammad haji aghajani1, ziba asadpoordezaki2,3, mehrdad haghighi4, asma pourhoseingoli1, niloufar taherpour1, amirmohammad toloui5, mohammad sistanizad1,6∗ 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of psychology, maynooth university, kildare, ireland. 3. kathleen lonsdale institute for human health research, maynooth university, kildare, ireland. 4. infectious diseases and tropical medicine research center, shahid beheshti university of medical sciences, tehran, iran. 5. physiology research center, iran university of medical sciences, school of medicine, tehran, iran. 6. department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. received: july 2021; accepted: august 2021; published online: 30 september 2021 abstract: introduction: adults with underlying medical disorders are at increased risk for severe illness from the virus that causes covid-19. this study aimed to compare the effect of underlying diseases on the mortality of male and female patients as a primary objective. we also evaluated the effect of drugs previously used by covid-19 patients on their outcome. methods: this retrospective cohort study was carried out on confirmed cases of covid-19 who were admitted to a teaching hospital in tehran, iran. data was gathered from patients’ files. log binomial model was used for investigating the association of underlying diseases and in-hospital mortality of these patients. results: a total of 991 patients (mean age 61.62±17.02; 54.9% male) were recruited. hypertension (41.1%), diabetes mellitus (30.6%), and coronary artery disease (19.6%) were the most common underlying diseases. the multivariable model showed that hypertension (rr = 1.62; 95% ci: 1.22-2.14, p = 0.001) in male patients over 55 years old and coronary artery disease (rr = 2.40; 95% ci: 1.24-4.46, p = 0.009) in female patients under 65 years old were risk factors of mortality. in females over 65 years old, the history of taking angiotensin converting enzyme inhibitors (acei) and angiotensin receptor blockers (arb) (rr = 0.272; 95% ci: 0.17-0.41, p = 0.001) was a significant protective factor for death. conclusion: covid-19 patients with a history of cardiovascular diseases such as hypertension and coronary artery disease, especially those in specific age and sex groups, are high-risk patients for in-hospital mortality. additionally, a previous history of taking acei and arb medications in females over 65 tears old was a protective factor against in-hospital mortality of covid-19 patients. keywords: covid-19; hypertension; coronary artery disease, prognosis cite this article as: haji aghajani m, asadpoordezaki z, haghighi m, pourhosseingoli a, taherpour n, toloui a, sistanizad m. effect of underlying cardiovascular disease on the prognosis of covid-19 patients; a sex and age-dependent analysis. arch acad emerg med. 2021; 9(1): e65. https://doi.org/10.22037/aaem.v9i1.1363. ∗corresponding author: mohammad sistanizad; 3rd floor, faculty of pharmacy, shahid beheshti medical university, vali-e-asr ave, niyayesh junction, tehran, iran. postal code, 1991953381, email: sistanizadm@sbmu.ac.ir, tel: +98-9122784895, fax: +98-2188200087, orcid: http://orcid.org/0000-00027836-6411. 1. introduction coronaviruses are a large family of viruses that are known to cause illnesses ranging from the common cold to more severe diseases such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars)(1, 2). the severe acute respiratory syndrome coronavirus 2 (sarscov-2), which causes covid-19 was first reported in wuhan, china, in late december 2019 (3). covid-19 has spread this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 2 worldwide leading to a global pandemic, it affects different areas of human life such as health, social, and economy, and had caused 93,805,612 confirmed cases and 2,026,093 deaths, by 18 january 2021 (4). adults with underlying medical disorders are at increased risk for severe illness from the virus that causes covid-19. cardiovascular disease (cvd) is one of the most important underlying diseases, which could affect the prognosis of patients with covid-19 (5). in addition, a high rate of underlying cvd has been observed in patients with covid-19, and increased mortality rates have been reported with these comorbidities (6, 7). from the point of view of studies from different countries, age and sex are considered to be strong prognostic factors of death in patients with covid-19. sex difference in covid19 outcome results from an interlock interaction between biological, geographical, and social impacts, and past medical history including preexisting cvd. this study aimed to compare the effect of underlying disease on the mortality of male and female patients as a primary objective. we also evaluated the effect of drugs previously used by covid-19 patients, including beta blockers, angiotensin converting enzyme inhibitors (acei), angiotensin receptor blockers (arb), anticoagulants, and antiplatelet drugs, on their outcome. 2. methods 2.1. study design and setting the present study was a retrospective cohort study conducted on 991 confirmed covid-19 patients with hospitalization criteria in imam hossein hospital, affiliated to shahid beheshti university of medical sciences, tehran, iran. the current study was performed based on helsinki declarations and was approved by the reviewer’s board and ethics committee of the deputy for research affairs, shahid beheshti university of medical sciences, tehran, iran (ethics code: ir.sbmu.retech.rec.1399.263). 2.2. participants using the census method, all of the patients who were admitted from 29 february to 20 july 2020 with a laboratory confirmed sars-cov2 infection based on reverse transcriptase polymerase chain reaction test (rt-pcr) using throat and nose swab specimens were included in this study. confirmed covid-19 outpatients and the patients with the clinical diagnosis of covid-19 whose diagnosis was not confirmed by pcr test were excluded from the study. 2.3. follow-up and outcome in this study, the measured outcome was in-hospital mortality and follow-up time was the duration of hospitalization, which is from the date of admission to date of discharge or when the patient died during hospitalization. 2.4. data gathering data were collected from medical records of covid-19 patients using a researcher-made checklist. researchers designed a checklist based on the aim of the study according to the opinion of medical and methodological expert team. data extracted for each patient included demographic characteristics (age, sex), body mass index (bmi), past medical histories such as underlying diseases and medication history, signs and symptoms on admission, duration of hospitalization, and outcome of patients such as intensive care unit (icu) admission, and in-hospital mortality. the mentioned information was extracted from medical records of covid19 patients by a trained research team that included nursing and medical personnel of cardiac care unit (ccu) and icu. 2.5. definitions in this study, underlying diseases were defined as chronic health conditions that patients already had before their hospitalization due to covid-19 infection. candidate underlying diseases were diabetes mellitus (dm), central nervous system (cns) disorders, hypertension (htn), chronic kidney diseases (ckds), any type of cancer, hyperlipidemia, immunosuppressive disorders, respiratory diseases, congenital disorders, coronary artery diseases (cads), and history of coronary angioplasty or coronary artery bypass graft (cabg) surgery. the information from the mentioned diseases was based on the reports of physicians’ examination. medication history referred to the patients’ use of different types of drugs due to their special health conditions, based on a physicians’ prescription, before hospitalization due to covid-19 infection. in this study, the studied medications were beta blockers, acei or arb, asa (acetyl salicylic acid), atorvastatin, nitroglycerin, warfarin, rivaroxaban, and metformin. 2.6. statistical analysis continuous variables were described using mean ± standard deviation (sd), and categorical variables were expressed as frequency (percentage). the normality assumption was examined using checking kurtosis, skewness, box plot, and q-q plot, due to the large amount of data. t-test and mann–whitney u test were used for comparisons of means in normal and non-normal variables, respectively. in addition, a multivariable log binomial regression model was performed for investigating the association of in-hospital mortality with underlying diseases and other variables of the study. the final multivariable model was selected based on potential risk factors according to the backward approach with p-value < 0.2. due to the proven role of sex and age in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e65 the etiology of disease and its prognosis, we used subgroup analysis to consider the probable effect of these interactive biological variables. in subgroup analysis, the age cut-offs considered for males and females were 55 and 65 years, respectively (8). findings were reported as relative risk (rr) and 95% confidence interval (95% ci). a two-sided p-value less than 0.05 was considered statistically significant. analyzing was done using the stata 14 package. 3. results 3.1. demographic characteristics and clinical findings among the 991 patients, 544 (54.9%) were male and 257 patients (25.9%) died. the mean age was 61.62±17.02 years [range 10-99]. the most common chief complaints were dyspnea with 626 (63.2%), cough with 524 (52.9%), fever with 495 (49.9%), myalgia with 320 (32.3%), nausea/vomiting with 204 (20.6%), and diarrhea with 90 (9.1%) cases. the median duration of hospitalization was 6 days with an inter quartile range (iqr) of 6. one hundred eighteen (11.9%) patients were admitted to icu. table 1 shows the distribution of demographic and some clinical characteristics of studied cases. 3.2. underlying diseases and past cardiovascular medications hypertension with 407(41.1%), diabetes mellitus with 303(30.6%), and cad with 194(19.6%) cases were the most frequent underlying diseases in both sexes. in the first step of investigating the association of the underlying diseases with death in our whole population of covid-19 patients, the univariate analysis showed that cns disorders (17.2% vs 8.6% in dead and alive patients, respectively with p <0.001), htn (53.7% vs 36.6% dead and alive patients, respectively with p <0.001), and cad (25.7% vs 17.4% dead and alive patients, respectively with p <0.001) were underlying diseases associated with death. also, having a history of using asa (25.2% vs 18.7% dead and alive patients, respectively with p = 0.026), nitroglycerin (10.5% vs 6.3% dead and alive patients, respectively with p = 0.027), and warfarin or rivaroxaban (7% with 2.9% dead and alive patients, respectively with p = 0.003) had a significant association with mortality in our whole population. tables 2 and 3 show the association between underlying diseases and history of using cardiovascular medications with mortality of patients based on their sex. in the next step of designing a model, we fitted a multivariable model, adjusting the effects of demographic factors. in this model, only demographic factors of sex and age had a significant association with death. accordingly, we have noticed the strong effect of sex and age and their interactions on this model. to adjust their interaction effects precisely and to know how underlying diseases affect mortality in each sex, we have analyzed the relation between mortality, underlying diseases and medication history in different age and sex subgroups. our final multivariable models were fitted in four different sex and age groups. a total number of 257 females under 65, 190 females over 65, 199 males under 55, and 345 males over 55 were our subgroups in the final model. for males over 55 years old, htn was a significant risk factor in both univariate and multivariable analyses with rr: 1.34 (95% ci: 1.03-1.74, p=0.029) and rr: 1.62(95% ci: 1.222.14, p=0.001), respectively. there was no variable that significantly associated with mortality in males under 55 years old. in females under 65 years old, cad with rr: 3.01(95% ci: 1.55-5.84, p=0.001) in univariate analysis, and rr: 2.40 (95% ci: 1.24-4.46, p=0.009) in multivariable analysis was a remarkable risk factor of death on both analyses. although the history of taking acei or arb with rr: 2.16 (95% ci: 1.18-4.03, p=0.012), and atorvastatin with rr: 2.45(95% ci: 1.29-4.67, p=0.006) were significant risk factors in univariate analyses, they were not significant in multivariable analysis. in females over 65 years old, history of taking acei or arb was a significant protective factor against death in both univariate and multivariable analyses with rr: 0.521 (95% ci: 0.32-0.83, p=0.007) and rr: 0.272 (95% ci: 0.17-0.41, p=0.001), respectively. the results of univariate and multivariable models are shown in table 4. 4. discussion in this retrospective cohort study, we investigated the association between underlying cardiovascular diseases, patients’ drug history, and covid-19 mortality. we found that in males older than 55, htn and in females under 65, coronary artery disease was strongly associated with in-hospital mortality. additionally, a previous history of taking acei and arb medications in females over 65 were protective factors against in-hospital mortality of covid-19 patients. there are several studies on the assessment of the relationship of a history of htn and severity of covid-19 and its related mortality. several studies showed that htn is a risk factor for covid-19-related mortality. for example, a cohort study showed that hypertensive covid-19 patients have more severe inflammatory responses to the disease and experience more severe internal organ injury. poor outcome in hypertensive patients was more prevalent than nonhypertensive covid-19 patients (9). meanwhile, other studies demonstrated that there was no adequate evidence supporting the prognostic effect of htn for covid-19 (10). our results showed that htn is a risk factor for mortality only in males older than 55 years. this finding justifies the inconsistency between the studies. because hypertension seems to be a risk factor for patient mortality in a certain group of pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 4 table 1: baseline characteristics based on final disease outcome variables total (n:991) discharged (n:734 ndeath ((n:257 p-value sex (%) female 447(45.1) 347(47.3) 100(38.9) 0.020* male 544(54.9) 387(52.7) 157(61.1) age ( year) mean ± sd 61.62±17.02 58.45±16.75 70.84±14.23 <0.001* signs and symptoms dyspnea 626(63.2) 458(62.4) 168(65.4) 0.395 cough 524(52.9) 396(54) 128(49.8) 0.252 fever 495(49.9) 374(51) 121(47.1) 0.285 myalgia 320(32.3) 260(35.4) 60(23.3) 0.001* nausea/ vomiting 203(20.5) 153(20.8) 50(19.5) 0.635 diarrhea 90(9.1) 73(9.9) 17(6.6) 0.110 icu admission yes 118(11.9%) 44(6%) 74(28.8%) <0.001* no 183(71.2%) 690(94%) 873(88.1%) bmi(kg/m2) median (iqr) 26.17(5.31) 26.23(5.18) 25.92(5.87) 0.170 hospital stay (day) median (iqr) 6(6) 6(5) 6(7) 0.338 data are presented as mean ± standard deviation (sd), number (%) or median (inter quartile range). * p<0.05 was statistically significant. bmi: body mass index; icu: intensive care unit; iqr: inter quartile range. table 2: distribution of underlying diseases and their crude association with in-hospital mortality between sex groups in covid-19 patient variables male (n=544) female (n:447) survived dead p survived dead p dm 112(28.9) 50(31.8) 0.50 106(30.5) 35(35.0) 0.39 cns 44(11.4) 32(20.4) 0.006* 19(5.5) 12(12.1) 0.02* hypertension 121(31.3) 76(48.4) <0.001* 148(42.7) 62(62.0) <0.001* ckd 36(9.3) 16(10.2) 0.74 34(9.8) 16(16.0) 0.08 cancer 9(2.3) 7(4.5) 0.18 20(5.8) 6(6.0) 0.92 hyperlipidemia 19(4.9) 12(7.6) 0.213 21(6.1) 10(10.0) 0.17 isd 9(2.3) 7(4.5) 0.18 16(4.6) 5(5.0) 0.87 rd 27(7.0) 16(10.2) 0.20 31(8.9) 13(13.0) 0.22 cd 5(1.3) 4(2.5) 0.29 10(2.9) 2(2.0) 0.63 cad 77(19.9) 36(22.9) 0.42 51(14.7) 30(30.0) <0.001* coronary revisualization cabg 31(8.0) 12(7.6) 0.82 7(2.0) 7(7.1) 0.003* angioplasty 24(6.2%) 12(7.6%) 11(3.2%) 8(8.2%) data are presented as number (%). dm: diabetes mellitus; cns: central nervous system disorders; ckd: chronic kidney disease; isd: immunosuppressive disorders; rd: respiratory diseases; cd: congenital disorders; cad: coronary artery disease; cabg: coronary artery bypass graft; p<0.05 was considered statistically significant. tients, not for all covid-19 patients. to be illustrated, our findings are in line with previous research, confirming the prognostic value of age in predicting covid-19 patients’ disease severity and its pertaining mortality (11). moreover, we have concluded that the male sex is independently associated with a higher risk of death in covid-19 patients. evidence regarding the impact of sex on in-hospital mortality of covid-19 patients is a growing topic and so far, independent association of male sex with mortality has been shown in some studies (12-14). reasons behind this finding could be the higher levels of humoral and cellular immunity in females and possible differences in sex-based comorbidities (14-19). underlying cardiovascular disease was a risk factor of inhospital mortality in female patients aged less than 65 years. it has been previously shown that premenopausal females who develop coronary artery disease might have lower levels of estrogen compared to those without coronary artery disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e65 table 3: distribution of past cardiovascular medications and their crude association with in-hospital mortality between sex groups among covid-19 patient variables male (n=544) female (n:447) survived dead p survived dead p beta blockers 51(13.2) 20(12.7) 0.862 57(16.4) 28(28) 0.009* acei or arb 82(21.2) 38(24.1) 0.473 106(30.5) 31(31) 0.931 asa 79(20.5) 42(26.6) 0.119 58(16.7) 23(23) 0.151 atorvastatin 54(14) 25(15.8) 0.582 66(19) 25(25) 0.191 nitroglycerin 29(7.5) 13(8.2) 0.582 17(4.9) 14(14) 0.002* warfarin/rivaroxaban 12(3.1) 8(5.1) 0.271 9(2.6) 10(10.0%) 0.003* data are presented as number (%). * p<0.05 was statistically significant. acei: angiotensin converting enzyme inhibitor; arb: angiotensin receptor blocker; asa: acetyl salicylic acid. table 4: univariate and multivariable analysis results for the association of underlying disease and drug history with in-hospital death in patients with covid-19 in different age and sex subgroups variables univariate multivariable rr (95% ci) p rr (95% ci) p males over 55 years old** hypertension no 1 1 yes 1.34(1.03-1.74) 0.029* 1.62(1.22-2.14) 0.001* taking beta blocker no 1 1 yes 0.77(0.51-1.14) 0.200 0.68(0.46-1.02) 0.063 taking acei or arb no 1 1 yes 0.89(0.66-1.02) 0.446 0.74(0.54-1.01) 0.063 females under 65 years old coronary artery disease no 1 1 yes 3.01(1.55-5.84) 0.001* 2.40(1.24-4.64) 0.009* taking atorvastatin no 1 1 yes 2.45(1.29-4.67) 0.006* 1.74(0.90-3.37) 0.096 taking acei or arb no 1 1 yes 2.16(1.18-4.03) 0.012* 1.72(0.92-3.20) 0.085 females over 65 years old hypertension no 1 1 yes 1.10(0.72-1.70) 0.643 1.16(0.912-1.75) 0.086 taking acei or arb no 1 1 yes 0.521(0.32-0.83) 0.007* 0.27 (0.17-0.41) <0.001* chronic kidney disease no 1 1 yes 1.51(0.969-2.33) 0.068 1.34(0.945-2.39) 0.067 ci: confidence interval. *p<0.05 was considered statistically significant. **all variables were excluded in the final model of the subgroup of males under 55 years old. acei: angiotensin converting enzyme inhibitor; arb: angiotensin receptor blocker. ease (20-22). besides, there is growing evidence on the protective effect of estrogen hormone against covid-19 (23-26). considering that the most important factor responsible for higher levels of immune system activity in females is probably hormonal differences, there seems to be a correlation between lower estrogen levels, higher incidence of cad, more this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. haji aghajani et al. 6 susceptibility to developing severe disease from sars-cov-2 infection, and higher mortality rates. growing evidence suggests that taking anti-hypertensive drugs (acei/arb) is not associated with higher mortality rates or illness severity in covid-19 patients and in fact, it might be beneficial for these patients. we demonstrated that the history of taking these drugs has a protective impact against the mortality of females more than 65 years old, in line with other studies showing a possibly lower mortality rate in patients treated with these medications (6, 27-30). however, the effects of taking these medications haven’t been completely studied in different ages and sexes. due to complexity regarding confounding factors of underlying diseases and biological changes, especially in females during postmenopausal period, more studies are required to assess the effects of these drugs in specific age categories. 5. limitations this retrospective study had its limitations. due to its nature, tools to evaluate patients’ data documentation were not available; some data such as previous medication history were recorded according to patients’ self-report and, therefore, were not totally reliable. previous medical files of patients were inaccessible due to the shortage of time and supplies during the pandemic. 6. conclusion covid-19 patients with a history of cardiovascular diseases such as hypertension and coronary artery disease, especially those in specific age and sex groups, are high-risk patients for in-hospital mortality. additionally, a previous history of taking acei and arb medications in females over 65 were protective factors against in-hospital mortality of covid-19 patients. 7. declarations 7.1. acknowledgments the authors express their appreciation to the participants and the personnel of imam hossien hospital for their collaboration. we acknowledge the team of professional nurses of shahid beheshti university of medical science for their effort in data collection (mrs. golnoosh mortezaee, effat taheri, ghodsi najari, faezeh nesaei, faezeh fakour, ghazaleh amanabadi, and vida torabi) and maedeh sayad for dedication to data entry. 7.2. funding this work was supported by the prevention of cardiovascular disease research center, shahid beheshti university of medical science, tehran, iran. 7.3. conflict of interest statement the authors have declared that no competing interests exist. 7.4. author contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. references 1. swerdlow dl, finelli l. preparation for possible sustained transmission of 2019 novel coronavirus: lessons from previous epidemics. 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downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e30 https://doi.org/10.22037/aaem.v9i1.1140 or i g i n a l re s e a rc h high incidence of workplace violence in metropolitan emergency departments of thailand; a cross sectional study adisak nithimathachoke1∗, wanawat wichiennopparat1 1. department of emergency medicine, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand 10300. received: january 2021; accepted: february 2021; published online: 25 march 2021 abstract: introduction: violence against healthcare workers mostly occurs in emergency departments and is a serious global public health issue. this study aimed to evaluate the prevalence of violence directed towards emergency department healthcare personnel and to ascertain the factors that might be correlated with it. methods: in this cross-sectional study, an anonymous questionnaire was used to gather data from healthcare personnel working in the emergency departments under the direction of the bangkok metropolitan administration between 1 august 2019 and 30 november 2019, regarding the experience of violence during the previous year. results: a total of 258 (87.5%) responses were received from 295 personnel. the results showed that 88.4% (228 personnel) had experienced violence during the past year, of these, 37.6% involved physical abuse that caused minor injuries. employees with shorter tenures, nurses, and those working in tertiary academic emergency departments in the central business district were found to have increased likelihood of confronting violence. measures taken to prevent violence had a limited impact on the occurrence rate. the most common impact on employees after experiencing violence was discouragement in their jobs (75.1 %). the key factors that promoted cases of violence were the consumption of alcohol or drugs (81.3%) and long waiting times (73.6%). most violence tended to occur during non-office hours (95.4%). one-third of emergency healthcare personnel reported facing violence during their work. conclusion: emergency healthcare personnel in metropolitan of thailand had a high rate of experiencing violence in the previous year. younger age, lower work experience, being a nurse, and working in the urban academic or tertiary emergency department increased the likelihood of being a victim of workplace violence. keywords: emergency department; factors; hospital; personnel; prevention measure, violence cite this article as: nithimathachoke a, wichiennopparat w. high incidence of workplace violence in metropolitan emergency departments of thailand; a cross sectional study. arch acad emerg med. 2021; 9(1): e30. 1. introduction healthcare providers are more likely to experience workplace violence than any other service occupations. additionally, workplace violence in the health sector is a global public health issue (1, 2). emergency departments (ed) are recognized as a high-risk area for violence against healthcare personnel and many studies reported a high occurrence of aggression initiated by patients or their relatives (3-7). an emergency department has many factors that might aggra∗corresponding author: adisak nithimathachoke; department of emergency medicine,681 m floor, petcharatch building faculty of medicine vajira hospital, samsane road, achiraphayaban, dusit, bangkok, thailand 10300. phone: +66-2-244-3189, mobile: +66-8-7694-6294, e-mail: adisak@nmu.ac.th. vate violent behaviors: long waiting times, crowding, various patient conditions, and substance use (8, 9). workplace violence is related to job dissatisfaction, burnout, and turnover rate (10). violence also results in psychiatric problems and physical injury, which impact both the personnel and their organizations and ultimately affect the care of patients. many works of literature emphasize using tools to minimize violence such as risk assessment, incident reports, and security systems (5, 11-15). most of them show inconclusive results in practice, though statistically significant outcomes in training sections have been reported in some studies (1620). laws have been passed to help mitigate the issue in some regions. however, the incidence of violence directed toward healthcare personnel continues to increase (21-24). a study on violence against nurses working in emergency department was published 10 years ago, and only one ruthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. nithimathachoke and w. wichiennopparat 2 ral and one urban emergency department were included (6). our study aimed to examine the occurrence rates and characteristics of violence directed at healthcare professions in the eds of metropolitan thailand. moreover, the use of preventive measures and factors inducing violence were also explored. 2. methods 2.1. study design and setting in this cross-sectional study, an anonymous questionnaire was used to gather data from healthcare personnel working in the emergency departments under the direction of the bangkok metropolitan administration, regarding the experience of violence during the previous year. the data was collected between 1 august 2019 and 30 november 2019, after receiving approval from vajira institutional review board (virb), faculty of medicine, vajira hospital, navamindradhiraj university and bangkok metropolitan administration human research ethics committee (bmahrec) (coa 036/2561) on november 7, 2018. once permission from the directors of participant hospitals was acquired, the study was explained to heads of each emergency department and all eligible participants. permission requests from individual participants were made simultaneously. 2.2. participants according to the report from the health system research institute of thailand, the study population consisted of 3,000 healthcare personnel working in emergency departements of goverment hospitals in bangkok,thailand. in the previous study, 84.7% of healthcare personnel suffered from violence in the emergency department (6). therefore, the minimum number of respondents in this survey was determined at 184 with a 95% confidence interval and 5% margin of safety. considering the potential of missing data or non-respondents, an additional 10% was added to the number of participants required to be enrolled. the total amount of the total amount of respondents who were needed came to 203 healthcare personnel came to 203 healthcare personnel. we selected all 9 eds of hospitals under the direction of the medical service department of bangkok metropolitan administration as the targets for the survey, which was conducted as a traditional paper-based survey. healthcare providers who worked in emergency departments at least 40 hours a week with at least 1-year of work experience in the emergency departments were eligible to participate. however, the full-time personnel who were not providing care for patients were considered to be excluded from the study. following the criteria, a total of 295 providers were qualified to take part in the survey, from whom we intended to collect data without randomization. 2.3. definition of violence violence in this study was comprised physical assault and psychological assault. a physical assault was the use of physical force with or without an object against a person to threaten or harm them i.e. punch, kick, bite, and push. a psychological assault, without the use of physical force, was defined as an act against another person’s mental well-being and included verbal threat, harassment, criticism, etc. the workplace violence definitions in this study were assimilated with the definitions outlined by the world health organization, which consisted of physical violence and verbal violence. physical violence was the use of physical force with or without an object against a person to threaten or harm i.e. punch, kick, bite, and push. verbal violence referred to the use of comments that were known to be humiliating, embarrassing, offensive, threatening, or degrading to another person including swearing and insults. 2.4. data collection questionnaires with instructions alongside contact information of the researchers were sent to the heads of the emergency departments. all responses in this survey were anonymous, the questionnaires were treated as confidential and it was impossible to trace back any data. an anonymous self-administrated questionnaire was modified from workplace violence in health sector country case studies research instruments survey questionnaire by ilo/icn/who/psi geneva 2003 (25) and reviewed by two members of faculty specializing in emergency medicine who were not involved in the study. testing was conducted with 10 providers who had experience in the emergency department to check whether the questionnaire was clear and could be understood correctly. subsequently, revisions were made for clarity. the questionnaire comprised 4 parts: demographic data, characteristics of violent incidents, consequences, and prevention measures in the emergency department. 2.5. data analysis the data was analyzed using ibm corp. released 2013. ibm spss statistics for windows, version 22.0. armonk, ny: ibm corp. the quantitative data were reported as mean and standard deviation, t-test was used in normal distribution and mann-whitney u test in non-normal distribution to analyze the correlation. the categorical data such as gender, working experience, and type of violence were reported in numbers and percentage. the chi-square test or fisher’s exact test was implemented to examine the correlation between each factor and experiences of violence where p-value < 0.05 represented statistical significance. logistic regression was performed to analyze the odds ratio for the statistically signifithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e30 table 1: characteristics, consequences, and aggravating factors of violence among studied participants variable number (%) victim of violence psychological violence 218 (85.7) physical violence 93 (37.6) emotional consequence anger 133 (51.6) desire to quit the job 107 (41.4) wish to work outside ed 87 (33.7) sadness 78 (30.2) shame 65 (25.2) physical consequence abrasion 64 (24.8) contusion 35 (13.5) work shift when violence occurred morning shift (8 am. to 4 pm.) 12 (4.6) evening shift (4 pm. to midnight.) 189 (73.3) night shift (midnight. to 8 am.) 57 (22.1) contributing factors drunkenness or drug consumption 210 (81.3) long waiting time 190 (73.6) crowding 167 (64.7) symptom or disease 130 (50.4) inadequate security system 100 (38.8) miscommunication 98 (38.0) stressful situation 79 (30.6) unexpected treatment result 67 (26.0) improper waiting area 50 (19.4) lack of privacy 35 (13.6) area the violence occurred triage area 135 (52.3) treatment area 107 (41.5) waiting area 16 (6.2) every violence was reported yes 82 (36.0) no 165 (64.0) *more than one answer per question was acceptable. ed: emergency department. cant independent variables. 3. results 3.1. baseline characteristics of participants the total response rate was 87.5% (258 out of 295 questionnaires). the participants were 60 physicians (23.3%), 187 nurses (72.5%) and 11 nurse aids (4.3%). the mean age of all participants was 31.2 years (s.d. = 8.16) and 78.3% were female. most of the participants were under 30 years of age with average work experience of 7.4 years (s.d. = 7.24). the most common amount of working experience among participants was 1 year. tertiary hospitals and one university hospital located in the central district area of bangkok were the workplaces of 68.2% of participants. the rest of the participants were working in secondary care hospitals located in the periphery of bangkok. although 87.5% completed the questionnaires, there were 37 non-respondents (including the incomplete questionnaires) in this survey, more than half of whom (57.8%) were working in the secondary hospitals. 3.2. workplace violence table 1 summarizes the characteristics, consequences, and aggravating factors of violence among studied participants. 88.4% of medical personnel were assaulted during the previous year. psychological violence happened far more than physical violence. even though psychological assistance was not considered necessary by any of the respondents, nearly half of them expressed feelings of discouragement to work in an emergency department. physical impacts were minor injuries for which medical treatment was not necessary. most of the violence occurred during non-office hours, while only 4.6% of the violence occurred in the morning shift (8 a.m. to 4 p.m.). the respondents stated that the triage area and treatment area were the places where most violence occurred. more than half of the participants claimed that drunkenness, long waiting times, crowding, and disease-related factors were contributing to violence. the answers to the openended question about violence aggravating factors were negligence of the administrative persons, vague laws on this issue, and social media effects. less than half of the medical personnel (36.0%) used their hospitals’ incident reporting systems, which were not useful in respondents’ perspectives. workplace violence, composed of physical assaults and verbal abuse, had occurred in case of the majority of participants during the previous year. among the three professions, the ratios of being subjected to physical violence were lowest in physicians (20%). whereas, 72.7% of nurse-aides were injured from both forms of violence. physical violence happened more in younger participants and who had less work experience. the variables that had a statistically significant association with the experience of both types of violence were age, job tenure, profession, and type of hospital. in contrast, the incidence rate of both categories of violence was not different between males and females (table 2). 3.3. correlations the relationship between age (p = 0.007), profession (0.031), work experience (p = 0.014), and type of emergency department (p = 0.026) and frequency of workplace verbal and physical violence was found to be statistically significant. the younger emergency providers and individuals who had less work experience tended to face workplace violence significantly more compared to the providers between 51-60 years of age and those who had worked in the emergency department for more than 10 years. nurses were prone to experience workplace violence more than other professions (or: 6.143; 95% ci: 1.460 to 18.078). the emergency perthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. nithimathachoke and w. wichiennopparat 4 table 2: correlation between baseline charactericts of participats and frequency of experiencing different types of violence variable type of violence both* (n=228) p verbal (n=218) p physical (n=93) p age (year) 21-30 144 (92.3) 136 (87.2) 68 (43.6) 31-40 59 (88.1) 0.007 58 (86.6) 0.047 18 (26.9) 0.016 41-50 21 (72.4) 20 (69) 6 (20.7) 51-60 4 (66.7) 4 (66.7) 1 (16.7) gender female 179 (88.6) 0.818 170 (84.2) 0.838 72 (35.6) 0.875 profession physician 48 (80.0) 43 (71.1) 12 (20.0) nurse 171 (91.4) 0.031 167 (89.3) 0.005 73 (39.0) 0.001 nurse aide 9 (81.8) 8 (72.7) 8 (72.7) experience (year) 1-5 93 (91.2) 86 (84.3) 45 (44.1) 5-10 90 (91.8) 0.014 89 (90.8) 0.021 34 (34.7) 0.038 > 10 years 45 (77.6) 43 (74.1) 14 (24.1) type of hospital university 71 (92.2) 70 (90.9) 27 (35.1) tertiary 91 (91.9) 0.026 88 (88.9) 0.004 47 (47.5) 0.003 secondary 66 (80.5) 60 (73.2) 19 (23.2) *: verbal + physical. data are presented as number (%). table 3: predictors and the likelihood of experiencing workplace violence during the previous year among studied cases variable experience of violence p or 95% ci no (n=30) yes (n=228) age (year) 21-30 12 (4.7) 144 (55.8) 6.011 0.995 36.176 31-40 8 (3.1) 59 (22.9) 0.007 3.687 0.579 23.476 41-50 8 (3.1) 21 (8.1) 1.312 0.220 8.624 51-60 2 (0.8) 4 (1.6) ref profession physician 12 (3.1) 48 (20.2) 1.809 1.024-11.437 nurse 16 (7.8) 171 (64.7) 0.031 6.143 1.460-18.078 nurse aide 2 (0.8) 9 (3.5) ref work experience (year) 1-5 9 (3.5) 93 (36.1) 2.848 1.102-7.360 5-10 8 (3.1) 90 (34.9) 0.014 3.010 1.145-7.917 > 10 13 (5.0) 45 (17.4) ref type of hospital university hospital 6 (2.3) 71 (27.5) 2.431 1.059-7.769 tertiary hospital 8 (3.1) 91 (35.3) 0.026 2.746 1.115-6.823 secondary hospital 16 (6.2) 66 (25.6) ref or: odds ratio, ref: reference, ci: connfidence interval. data are presented as number (%). sonnel who worked in the tertiary (or: 2.746; 95% ci: 1.115 to 6.823) and in the university emergency departments (or 2.431; 95% ci: 1.059 to 7.769), located in the central business district of bangkok, were more likely to experience violent acts than were those working in secondary emergency departments, which were located in the periphery of bangkok (table 3). 3.4. prevention measures the prevention measure presented in most eds was the authorized access entrance (81.4%). however, less than half of the participants (32.6%) reported having security guards at the entrance of their eds and 8.5% had police activating systems. none of the respondents reported having any weapon screening measures before patients or visitors entering the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e30 table 4: relationship between existence of preventive measures and experience of physical violence violence prevention system n (%) experience n (%) p yes no authorized access entrance yes 210 (81.4) 79 (30.6) 131 (50.8) 0.319 guard at ed entrance yes 84 (32.6) 27 (10.5) 57 (22.1) 0.364 guard inside ed yes 14 (5.4) 9 (3.5) 5 (1.9) 0.979 police activating system yes 22 (8.5) 9 (3.5) 13 (5.0) 0.619 ed: emergency deparment; data are presented as number (%). eds. nonetheless, there was no association between having security systems and experience of physical violence. furthermore, all of the participants lacked training in workplace violence and there were no protocols for prevention or mitigation of aggression in their organizations (table 4). 4. discussion our study results show a significantly high rate of being violated amongst healthcare personnel working in metropolitan eds in thailand. this is consistent with the results from multinational studies (4, 8, 9, 19, 24-27). though workplace violence in the health sector is 15% to 20% higher than the other industries (2, 27), only 8-38% of providers in other healthcare settings experienced workplace violence (1, 28). the study in 2008 in southern thailand with 545 participants also found that only 38.9% of the nurses working in all departments were abused by verbal violence while 3.1% of them suffered from physical violence (29). the figures from the mentioned studies imply that an emergency department is a place where most violence in the hospital occurs. though none of the respondents had any serious physical injury from any weapon, the aggressions from patients or relatives are not acceptable. ignoring minor violence and verbal abuse could foster an environment that encourages more serious criminal events as stated in the broken windows theory (30). furthermore, the empirical results of this study suggested that when faced with violent acts, the participants mostly felt discouraged to continue working in the emergency departments. as stated in previous studies, these emotional consequences caused by violent experience could lead to depression, burnout syndrome, and eventually, drive the personnel to quit their jobs (10, 19, 31). moreover, a healthcare worker with emotional distress is more likely to be a victim of violence (27). the minority of the participants reported every time they had been violated, showing that the perception of the usefulness of the reporting system in thailand has not changed for years (6, 29). according to stene j.’s study, emergency department personnel perceived violence as part of their job, dismissing the opportunities to improve the risk reduction system. therefore, it is necessary to educate healthcare service providers about risk prediction, risk management, and risk report system as well as when to take legal action (5). non-office hours, specifically between 4 p.m. to midnight, were the time that almost all the violence occurred. according to the study by ferri p. et al., the evening shifts face inadequate manpower problems; and compared with other periods, more drunk and confused patients come to emergency departments during this period (32). these characteristics of emergency departments in non-office hours were similar to the violence aggravating factors specified by the respondents in the present study. in the previous studies in thailand, the majority of violent acts had happened during nonoffice hours. moreover, the factors that triggered most violence were similar to this study (1, 6, 29, 32). the report from the american college of emergency physicians (acep) (13) suggested that factors that promoted violence tended to increase upon the growth of delinquency and drug consumption. other contributing factors included healthcare facilities’ inadequacy in providing psychiatric counseling services during non-office hours, inability to admit psychiatric patients as an inpatient, and refusal to grant patient’s request for specific treatment and medication. dynamic management could be more helpful than fixed security measures such as increasing manpower during high patient volume periods, reducing waiting times, setting up a protocol for dealing with drunkenness, etc. in line with previous studies in the emergency departments, age, and work experience affected the likelihood of being a victim of violence among the emergency personnel, but males and females were similarly being subjected to workplace violence (3, 8, 26, 27). this finding was contrary to those of kowalenko t.’s research on violence against medical service providers in america and a study in india, which stated that female healthcare personnel were more prone to experiencing physical violence than their male counterparts this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. nithimathachoke and w. wichiennopparat 6 (33, 34). in the present study, nurses were most likely to be faced with workplace violence, which is consistent with previous reports in egypt and suburban eds in thailand (8, 35). the emergency providers who were younger and individuals who had less work experience confronted significantly more workplace violence compared to the more experienced group and those aged between 51-60 years, the reason for which could be the difference in total work hours each week and the pattern of shift work (35). though all of the emergency departments in this study were in the metropolitan of thailand, we found that working in tertiary and university emergency departments located in the central business district area increased the likelihood of being violated. this might be the effect of the patient volume. more than 50,000 visits annually at each tertiary emergency department and around 40,000 visits annually at each secondary facility. nevertheless, the results could have been different considering the number of non-respondents, more than half of whom worked in secondary hospitals. providers in our study encountered far more violence compared with 61.7% of violence in 472 participants in thai suburban emergency departments (35). currently, the data are inconclusive regarding location and type of emergency departments as risk factors. the emergency physician working in the high volume academic eds or the state eds in turkey are more likely to be a victim of workplace violence (27). whereas, 86% of australian nurses in the rural hospitals experienced violence compared to 43% of nurses working in the urban hospitals (36). besides, the healthcare providers in secondary level hospitals in china are more susceptible to aggression than those in primary and tertiary hospitals (37). nevertheless, a prospective study found no association between the level of hospital and experience of violence (38). the majority of emergency physicians in bangkok experienced violence, most of which were verbal abuse. merely, 20% of these physicians encountered physical violence while 7.7% of physicians who were working in eds in the suburban area of thailand had faced physical violence (35). this number is relatively low compared with 38.4% of emergency physicians in the united states who had experienced more physical violence based on a survey in 2018 (39). additionally, data from national judgment documents of china showed that doctors were the target group of violence and the majority of them were physically abused (4). these differences in results might be due to the different social structures such as the number of delinquencies, consumption of drugs, the law allowing citizens to carry weapons. although guidelines recommend using security tools to minimize workplace violence in the emergency departments (13, 14), not all of the emergency departments had these tools. particularly, none of the emergency departments in this study had a metal detector or weapon screening. however, none of the participants had experienced violence using any weapons. this is similar to prior researches in eds of thailand and italy (6, 35, 40). moreover, we found no relationship between having security systems and being a victim of aggression. while metal detectors markedly increased the rate of weapon detection, its impact on the occurrence of violence was not well established (19, 27). also, the presence of security guards does not decrease the incidence of violence (16). prediction of the aggressors and de-escalation methods have been used in hope of violent act prevention; however, no explicit data supports the efficacy of these measures (20). the complexity of workplace violence in emergency departments is well recognized. the actual occurrence rate and event details are important so an incident report should be emphasized. also, a comprehensive hazard analysis with multifaceted measures should be used in conjunction with support from executive authorities. the aggravating factors should be corrected simultaneously with the use of other prevention methods. additionally, quality improvement measures should be used to evaluate and improve the results. 5. limitations potential recall bias is the main limitation of this study. the questionnaires were developed and tested based on theory but it must be taken into account that the participants might answer each question based on their own interpretation. the participants were just a part of emergency department healthcare workers in bangkok, thailand and the actual occurrence rate might be different. besides, the individuals’ number of working hours and shift work patterns could affect their experience of violence, which were not examined in this study. a future study could focus on more aspects of aggravating factors that lead to violence against healthcare personnel working in emergency departments. the reduction of these factors along with current measures should also be investigated. 6. conclusion emergency healthcare personnel in metropolitan of thailand had a high rate of experiencing violence in the previous year, including thai emergency physicians whose data had not been explored before. younger age, less work experience, being a nurse, and working in the urban academic or tertiary emergency department increased the likelihood of being a victim of workplace violence. only a minority of emergency departments had the recommended violence prevention systems. however, the security measures are not related to workplace violence. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e30 7. declarations 7.1. authors’ contributions na: conceptualization, investigation, methodology, major contributor in writing the manuscript, supervision, and funding acquisition. ww: investigation, data collection, writing – original draft, and visualization. all authors read and approved the final manuscript. 7.2. competing interests the authors declare that they have no competing interests. 7.3. acknowledgments we are thankful to head of emergency department and participants from all bangkok-administrated hospitals who responded to the questionnaires and allowed the researchers to collect the data that will be of great benefit to future studies and promote safety culture in the healthcare system. we would also like to show our gratitude to bangkok metropolitan administration human research ethic committee (bmahrec) who provided insight reviews and comments. 7.4. funding and supports this study was sponsored by navamindradhiraj university research program, funding body was not involved in any part of the study. 7.5. availability of data and materials the data that support the findings of this study are available from the corresponding author, [adisk 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http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e47 or i g i n a l re s e a rc h emergency department quality dashboard; a systematic review of performance indicators, functionalities, and challenges sohrab almasi1, reza rabiei1, hamid moghaddasi1∗, mojtaba vahidi-asl2 1. department of health information technology and management, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. faculty of computer science and engineering, shahid beheshti university, tehran, iran. received: april 2021; accepted: may 2021; published online: 17 june 2021 abstract: introduction: effective information management in the emergency department (ed) can improve the control and management of ed processes. dashboards, known as data management tools, efficiently provide information and contribute greatly to control and management of ed. this study aimed to identify performance indicators quality dashboard functionalities, and analyze the challenges associated with dashboard implementation in the ed. methods: this systematic review began with a search in four databases (web of science, pubmed, embase, and scopus) from 2000 to may 30, 2020, when the final search for papers was conducted. the data were collected using a data extraction form and the contents of the extracted papers were analyzed through ed performance indicators, dashboard functionalities, and implementation challenges. results: performance indicators reported in the reviewed papers were classified as the quality of care, patient flow, timeliness, costs, and resources. the main dashboard functionalities noted in the papers included reporting, customization, alert creation, resource management, and real-time information display. the dashboard implementation challenges included data sources, data quality, integration with other systems, adaptability of dashboard functionalities to user needs, and selection of appropriate performance indicators. conclusion: quality dashboards facilitate processes, communication, and situation awareness in the ed; hence, they can improve care provision in this department. to enhance the effectiveness and efficiency of ed dashboards, officials should set performance indicators and consider the conformity of dashboard functionalities with user needs. they should also integrate dashboards with other relevant systems at the departmental and hospital levels. keywords: emergency service, hospital; quality indicators, health care; data management; systematic review cite this article as: almasi s, rabiei r, moghaddasi h, vahidi-asl m. emergency department quality dashboard; a systematic review of performance indicators, functionalities, and challenges. arch acad emerg med. 2021; 9(1): e47. https://doi.org/10.22037/aaem.v9i1.1230. 1. introduction since the emergency department (ed) provides complex services and hosts patients in critical physical conditions, timely and precise service provision in ed is considered a challenge(1). moreover, the increased number of visits to the ed disrupts emergency care provision in this department(2, 3). these problems lead to negative outcomes for both patients (morbidity and mortality) and healthcare providers in ∗corresponding author: hamid moghaddasi; department of health information technology and management, school of allied medical sciences, darband st, qods square, shariati st, tehran, iran. phone number: (+98) 21 22747373, fax: (+98) 21 2272 115, e-mail: moghaddasi@sbmu.ac.ir, orcid: https://orcid.org/0000-0002-5906-0329. the ed (stress and burnout)(4). effective information management in the ed provides timely information and improves process control and management in this department (5). the use of information technology in the ed plays a pivotal role in information management and enhances managerial and treatment-related processes(6). however, such systems are either not used at all or designed in a way that they further increase the workload of healthcare providers in the ed(7). research shows that although these systems promote coordination and communication among healthcare providers, they fail to offer rapid access to patient information, delay information recording, and have poor user-friendliness.(8) a poor user interface design is another disadvantage of ed information systems, which can cause users to face problems in accessing the necessary information (9, 10). dashboards, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 2 known as data management tools in the ed, collect data from various information systems including the ed, laboratory, and radiology information systems and display them based on pre-defined key performance indicators. using dashboards, ed managers evaluate the performance of their department, identify problems, analyze their causes, and thus promote their own performance(11). by displaying information through visual tools, dashboards help managers visually identify trends and patterns. the use of quality dashboards in the ed also facilitates work processes, reduces hospitalization duration, better demonstrates the ed status, improves coordination, enables rapid access to information, decreases complications for patients, promotes the monitoring of performance indicators by managers, enhances reporting flexibility, and provides timely information (12, 13). the key to a suitable design is paying attention to functionalities and performance indicators monitored by dashboards. dashboard functionalities demonstrate the system operations or the activities performed/facilitated by these operations (12). classified as a type of dashboard, the quality dashboard collects information from various sources and, by using visual tools based on key performance indicators, provides information at the level of department or organization to help users with decision-making (12-14). quality dashboards include those of the operating room (15), radiology (16), nursing (17), and intensive care unit (18). the use of dashboards enhances management of department processes, improves communications, and thus, aids decision-making. it is important to employ quality dashboards to obtain timely information for effective control and management of ed processes. for effective information management and communications in the ed, key performance indicators and functionalities of the quality dashboards should also be determined in terms of user needs (12, 19). this study aimed to identify ed performance indicators and quality dashboard functionalities, and analyze the challenges associated with their implementation in the ed. 2. methods 2.1. data sources and search strategy data search and extraction phases were performed based on the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist (20). the search formula was adopted through a combination of mesh terms, emtree, and keywords pertaining to dashboards and the ed (table 1). the search for finding relevant papers was conducted in four databases (embase, web of science, pubmed, and scopus) (table 2). the final search for papers was conducted on may 30, 2020. moreover, this study spanned from june 1 to december 30. one researcher (sa) independently searched and retrieved the papers, whereas uncertainties were discussed with the other two authors (rr and hm). the relevant papers were also retrieved through a search in google scholar and google. the search for papers was finalized with a bibliographic check of the designated papers. 2.2. inclusion and exclusion criteria the inclusion criteria were: 1) papers written in english; 2) papers on ed quality dashboards; and 3) papers on performance indicators and functionalities of ed quality dashboards. moreover, the exclusion criteria were: 1) non-english papers; 2) papers merely designing a clinical dashboard for the ed; or 3) papers examining the dashboards of other hospital wards. 2.3. paper selection, paper evaluation, and data extraction in the screening step, three authors (sa, rr, and hm) checked the titles and abstracts of the papers and irrelevant papers were removed. in the eligibility step, the papers were independently checked by the same noted authors. the bibliography check was then conducted by one of the authors (sa). the quality assessment of the papers based on cochrane effective practice and organization of care (epoc) guideline (21) was independently conducted by sa, rr, and hm. for data extraction, the performance indicators of the ed were first extracted from the papers. the performance indicators used by the ed quality dashboards mentioned in the reviewed papers were classified as patient flow, timeliness, quality of care, costs, and resources (table 3) (22). the first author’s name, the year of publication, the place of study, the quality dashboard functionalities, and the main challenges associated with using the dashboard in the ed were then extracted from each paper (table 4). 3. results a total of 1275 papers were retrieved through the search in databases. additionally, four papers were retrieved from a search attempt on google scholar and google. after removing the duplicates using endnote software, 484 papers remained. the titles and abstracts of the papers were then reviewed. as a result, 423 papers were removed and 61 remained. in the next step, the full texts of papers were checked and this resulted in the removal of 42 papers. ultimately, 18 papers remained for analysis. one more paper was also retrieved when performing a bibliographic check of the designated papers. no paper was removed after quality assessment, and all the papers entered the final analysis phase. finally, 19 papers were reviewed in this study. figure 1 displays the paper selection process. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e47 3.1. quality assessment according to the quality assessment of papers, three studies (19, 23, 33) were considered as “high quality”; four studies (24, 25, 31, 37) were introduced as “fair to good quality”, and 12 studies (11, 26-30, 32, 34-36, 38, 39) were regarded as low quality (table 5). 3.2. ed quality dashboard performance indicators the performance indicators (26 in total) were reported in five main categories (quality of care, patient flow, timeliness, costs, and resources). the majority of performance indicators were related to patient flow (8 indicators), timeliness (7 indicators), quality of care (4 indicators), and costs (2 indicators), respectively. the following indicators belonged to the patient flow category: the number of patients discharged and the type of discharge (referral to other centers, admission at the hospital) (in 11 papers), the total number of people visiting the ed (n=10), the number of patients in the ed (divided by age, gender, type of specialty, and triage level) (n=8), the number of patients admitted per triage level (n=6), how the patients visited the ed (personal vehicles, ambulance, on foot), and the number of patients for whom a decision was made in six hours (n=4). the timeliness category consisted of the following performance indicators: the patients’ mean length of stay (n=16), the time of triaging (per each triage level) (n=4), and the mean time elapsed since the patients’ arrival in the ed until the onset of triaging (n=4). only three out of the 19 papers had mentioned the quality of care performance indicators, which included patient revisits (before 72 hours) (n=3) and the percentage of mortality among the patients admitted to the ed (in=2). the cost performance indicators included the number of tests ordered by the doctors (n=8) and the number of consultations given (n=3). finally, resource performance indicators were the number of beds (available, extra, occupied, reserved, and out-of-order) (n=7) and the number of personnel in the ed (divided by discipline and gender) (n=6). 3.3. ed quality dashboard functionalities all the 19 papers discussed the reporting functionality. this was followed by customization (n=12) (11, 19, 23-32), alerting (n=10) (11, 25, 27, 29-35), resource management (n=9) (19, 24-29, 33, 36), and real-time information display (n=8) (11, 19, 24, 31, 33, 37-39) as the most frequently mentioned functionalities, respectively. other papers also reported functionalities such as automated data collection (n=4) (11, 29, 31, 39) and the use of drill-up, drill-down, and drill-through (n=4) (23, 25, 31, 33). 3.4. challenges to use of quality dashboards in ed the challenges associated with the use of quality dashboards in the ed included a lack of integration with other hospital systems and inputting the data manually (24, 29), lack of adaptability to work processes in the ed and lack of flexibility (26, 28, 30, 32-34, 37), breaching patient confidentiality by displaying patients’ names and test results on the dashboard’s large screen (27, 31), a problem with understanding and interpreting the type of information displayed through visualization tools (27, 28), and the accuracy of the data entered into the dashboard (23). 4. discussion this study aimed to identify the performance indicators, functionalities, and challenges of quality dashboards in the ed. some studies had examined the effects of clinical/quality dashboards on patient care improvement or analyzed the functionalities and positive and negative effects of using dashboards in hospital(40, 41). determining key performance indicators lays the ground for performance measurement, ensures progress evaluation based on pre-defined goals/criteria, and aids managers in decision-making by providing timely and appropriate information (42). based on the results of this study, ed performance indicators are divided into five groups of quality of care, patient flow, timeliness, costs, and resources. these findings are in line with the results of studies by sørup (22) and the us institute of medicine (43). since the patient-centeredness indicator deals with the provision of care based on patients’ needs, preferences, and values, this indicator was called patient flow in this study (43). safety deals with the perceived damage and complications of treatment processes. since the patient mortality indicator may not be related to treatment processes at the hospital and result from underlying diseases (44, 45), this indicator was replaced by the quality of care in this study. as for the quality dashboard functionalities, our findings yielded reporting, customization, real-time information display, resource management, and alerts. previous studies have introduced measurement, monitoring, collection, processing, performance measurement, and reporting as dashboard functionalities(40, 42, 46, 47). the ed has complex processes with its personnel having different information needs with respect to their responsibilities. therefore, it is essential to pay attention to quality dashboard functionalities and select suitable performance indicators to be monitored by the dashboard (40). the dashboard development challenges included data sources and data quality, integration with other systems, adaptability of dashboard functionalities to user needs, and selection of appropriate performance indicators. these findings are consistent with those this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 4 of ghazisaeidi et al. (48). the main challenge in integrating dashboards with other systems is mostly related to the information technology infrastructure in the organization, which focuses on data collection through different data sources, data integration, and their linkage to the dashboard through the most appropriate method. (49) designing a suitable architecture for supporting the dashboard requires identification of different data hosting structures, various methods of data replication and transfer, and the best query language for this data structure (50). moreover, the identification of data sources—the processes used for data generation— and precise, comprehensive, and reliable datasets for generating high-quality data are major topics in dashboard development, which increase ed users’ trust in dashboard information (48). research findings also demonstrate that continuous implementation with small changes can greatly contribute to the success of dashboard in meeting users’ needs(48, 50). 5. limitations there are limitations with the current study that could be addressed in future research. first of all, the current study reviewed studies published in english and there might be useful relevant studies that were excluded. in addition, although we systematically studied the key performance indicators of quality dashboard in the emergency department, we did not include studies that addressed clinical dashboards of this department due to aim of the study. in the analysis step, an attempt was made to avoid or minimize the risk of bias, as any possible discrepancy experienced by either of the first three authors were discussed in group. however, there may have been issues that did not catch our attention. 6. conclusion and suggestion the findings of the current study indicated that applying key performance indicators for ed quality dashboard, including quality of care, patient flow, timeliness, costs, and resources, could improve utilization management and quality of care. moreover, a quality dashboard should support functions such as customization, reporting, real-time information display, resource management, alert creation, and automated data collection. in addition, the use of drill-up, drill-down, and drill-through features could help improve efficiency and effectiveness of ed quality dashboard. with respect to the challenges noted, it is suggested that in further developments of ed dashboard, attention should be paid to data sources, the quality of data, and integration with other systems both in the ed and in other hospital departments. 7. declarations 7.1. acknowledgments none. 7.2. funding and support this systematic review did not receive any funding. 7.3. author contribution concept and study design: sa, rr, hm, mva; literature search, study selection and data collection: sa; analysis and interpretation: sa, rr, hm; writing the article: sa; critical revision of the article: rr, hm; final approval of the article: sa, rr, hm, mva. 7.4. ethical approval this review was part of a larger study, approved by the ethics committee of shahid beheshti university of medical sciences, iran (ir.sbmu.retech.rec.1399.565). 7.5. conflict of interest the authors declare that they have no competing interests. references 1. 1. steptoe ap, corel b, sullivan af, camargo ca. 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clinicians’ time distribution and mental workload. health informatics journal. 2016;22(1):3-20. 31. mazor i, heart t, even a. simulating the impact of an online digital dashboard in emergency departments on patients length of stay. journal of decision systems. 2016;25(sup1):343-53. 32. mcgeorge n, hegde s, berg rl, guarrera-schick tk, lavergne dt, casucci sn, et al. assessment of innovative emergency department information displays in a clinical simulation center. j cogn eng decis mak. 2015;9(4):329-46. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 6 33. dexheimer jw, kennebeck s. modifications and integration of the electronic tracking board in a pediatric emergency department. pediatric emergency care. 2013;29(7):852-7. 34. bisantz a, pennathur p, guarrera t, fairbanks r, perry s, zwemer f, et al. emergency department status boards: a 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the 21st century. washington (dc): national academies press (us); 2001. 44. diley i, badrinath p, annon s. is mortality a good indicator of the clinical quality of national health service hospitals? a cross-sectional study of outlier trusts for mortality indices using quality dashboards. jrsm open. 2014;5(8):2054270414533325. 45. ngantcha m, le-pogam m-a, calmus s, grenier c, evrard i, lamarche-vadel a, et al. hospital quality measures: are process indicators associated with hospital standardized mortality ratios in french acute care hospitals? bmc health services research. 2017;17(1):578-. 46. eckerson ww. performance dashboards: measuring, monitoring, and managing your business: john wiley & sons; 2010. 47. jeffs l, beswick s, lo j, lai y, chhun a, campbell h. insights from staff nurses and managers on unit-specific nursing performance dashboards: a qualitative study. bmj quality & safety. 2014;23(12):1001-6. 48. ghazisaeidi m, safdari r, torabi m, mirzaee m, farzi j, goodini a. development of performance dashboards in healthcare sector: key practical issues. acta informatica medica. 2015;23(5):317. 49. minnigh tr, gallet j. maintaining quality control using a radiological digital x-ray dashboard. j digit imaging. 2009;22(1):84-8. 50. rasmussen nh, bansal m, chen cy. business dashboards: a visual catalog for design and deployment: john wiley & sons; 2009. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e47 figure 1: flow diagram based on prisma. table 1: search formula no. terms search formula 1 dashboard “dashboard” or “electronic whiteboard” or “emergency department dashboard” or “emergency department information system” or “status board” or “electronic tracking board” 2 ed “emergency department” or “emergency” or “emergency medicine” or “emergency medical services” or “emergency unit” 3 1 and 2 ed: emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 8 table 2: search strategy database search terms pubmed (emergency department dashboard[tiab] or whiteboard[tiab] or emergency department information system[tiab] or status board[tiab] or electronic tracking board[tiab] or dashboard[tiab]) and (emergency department[mesh] or emergency department[tiab] or emergency[tiab] or emergency medicine[tiab] or emergency medical services[mesh] or emergency unit[tiab]) not review web of science ts=(dashboard or "electronic whiteboard" or “emergency department dashboard” or “emergency department information system” or "status board" or "electronic tracking board") and ts=("emergency department" or emergency or "emergency medicine" or "emergency medical services" or "emergency unit") embase (’emergency department dashboard’:ab,ti or whiteboard:ab,ti or ’emergency department information system’:ab,ti or dashboard:ab,ti or ’electronic tracking board’:ab,ti or ’status board’:ab,ti) and (’emergency ward’/exp/mj or ’emergency medicine’/exp/mj or ’emergency health service’/exp/mj or ’emergency ward’:ab,ti or ’emergency medicine’:ab,ti or ’emergency health service’:ab,ti) scopus ((title-abs (dashboard) or title-abs ( "electronic whiteboard" ) or title-abs ( "emergency department dashboard" ) or title-abs ( "emergency department information system" ) or title-abs ( "status board" ) or title-abs ( "electronic tracking board" ) ) and ( title-abs ( "emergency department" ) or title-abs ( emergency ) or title-abs ( "emergency medicine" ) or title-abs ( "emergency medical services" ) or title-abs ( "emergency unit" ) ) ) table 3: evaluated key performance indicators of emergency department in included articles authors patient flow timeliness 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 van deen et al. (23) p p p p hester et al.(24) p p p martin et al. (19) p p p p p p p p yoo et al. (11) p p franklin et al. (25) p p p p p p p p staib et al. (26) p hertzum et al. (27) p p p p mazor et al. (28) p p p p p p mcgeorge et al. (29) p p p p p p p p dexheimer et al. (30) p p p p p mcleod et al. (31) p p p p bisantz et al. (32) p p p p p p p p patterson et al. (33) p p p p p rasmussen et al. (34) p p aronsky et al. (35) p p p pennathur et al. (36) p p france et al. (37) p p p wears et al. (38) p p p boger (39) p p p p p 1. the total number of people visiting the ed 2. how patients visit the ed 3. the number of patients discharged, and the type of discharge 4. the number of patients based on the triage level 5. the number of patients leaving the ed without primary evaluation and treatment 6. the number of patients in the ed 7. the number of patients waiting to be visited 8. the number of patients discharged from the ed in six hours 9. the patients’ mean length of stay 10. the mean time elapsed since the doctor’s request for admission until the assignment of a room/bed to the patient in the inpatient ward 11 . the time of triaging (per each triage level) 12. the mean time elapsed since the patients’ arrival in the ed until the onset/beginning of triaging 13. the mean time elapsed since the patients’ arrival in the ed until admission at the ward 14. the mean time elapsed since the patients’ arrival in the ed until doctor’s visit 15. the mean time elapsed since the orders are recorded until the results (tests, imaging, electrocardiography) are ready. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e47 table 3: evaluated key performance indicators of emergency department in included articles (continued) authors quality of care costs resources 1 2 3 4 5 6 7 8 9 10 van deen et al. (23) p p p hester et al.(25) p p p martin et al. (19) p p yoo et al. (11) p p p franklin et al. (26) ! p p staib et al. (29) p p p p hertzum et al. (30) p mazor et al. (31) p mcgeorge et al. (32) p p p p dexheimer et al. (33) mcleod et al. (27) bisantz et al. (34) p p patterson et al. (24) p p rasmussen et al. (35) p p aronsky et al. (36) p p p p pennathur et al. (37) p france et al. (28) wears et al. (39) p p boger (38) 1. patients readmission (before 72 hours) 2. the percentage of mortality among the patients admitted to the ed 3. the number of heart attacks in 24 hours among the patients admitted through the ed 4. the percentage of mortality among the hospital’s patients admitted through the ed 5. the number of visits made 6. the mean number of visits made by the doctor per hour 7. the number of tests ordered by the doctors 8. the number of consultations given 9. the number of personnel in the ed (based on discipline and sex) 10. the number of beds (available, extra, occupied, reserved, out-of-order) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. almasi et al. 10 table 4: specifications of the dashboards examined in the papers author quality dashboard functionalities challenges van deen et al. (23) 2019; usa reporting drill-down and drill-up drill-through customization the data entered into the dashboard were not reliable or sufficiently accurate. hester et al.(24) 2019;denmark reporting real-time information display the designed dashboard functionalities were not compatible with the work processes of the healthcare providers in the ed. martin et al. (19) 2018; usa resource management reporting real-time information display customization n/a yoo et al. (11) 2018; south korea real-time information display automated data collection reporting alert customization the designed dashboard was evaluated only in one ed, and it might not be useful because of the hospital’s different specialties and the use of different performance indicators. franklin et al. (25) 2017; usa resource management alert reporting real-time information display drill-down and drill-up drill-through the information displayed by the dashboard did not meet the diverse needs of ed users. staib et al. (26) 2017; australia real-time information display reporting n/a hertzum et al. (27) 2016; denmark resource management reporting real-time information display customization the challenges included a lack of integration between the dashboard and the other systems at the hospital, and inputting the information manually. mazor et al. (28) 2016; israel alert resource management reporting customization drill-down and drill-up drill-through7 the research limitation was that the evaluation was performed in a simulated environment. mcgeorge et al. (29) 2015; usa reporting resource management customization the research limitation was that the evaluation was performed in a simulated environment. dexheimer et al. (30) 2013; usa resource management alert reporting customization a problem in interpreting the information displayed by the dashboard, and breaching confidentiality as some patient demographic information was displayed in the dashboard. mcleod et al. (31) 2010; canada real-time information display automated data collection reporting n/a bisantz et al. (32) 2010; usa resource management reporting customization a problem with understanding the type of information displayed in the dashboard, and the dashboard’s lack of adaptability to work processes and the doctors’ information needs patterson et al. (33) 2010; usa automated data collection resource management alert reporting customization lack of integration with other hospital systems, and inputting the data manually rasmussen et al. (34) 2010;denmark alert reporting customization lack of compatibility between the features of the new system and the work processes in the ed aronsky et al. (35) 2007; usa real-time information display automated data collection alert reporting customization drill-down and drill-up drill-through displaying information such as patient name and test results on the dashboard large screen violated patient information confidentiality. pennathur et al. (36) 2007; usa alert reporting customization lack of compatibility with workflows, especially during triaging and tracking the stages of care france et al. (37) 2005; usa resource management reporting n/a wears et al. (38) 2003; usa alert reporting low flexibility, no customization feature boger (39) 2003; usa reporting alert n/a ed: emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e47 table 5: risk of bias assessment in included studies based on effective practice and organization of care (epoc) tools variable 1 2 3 4 5 6 7 van deen et al. (23) p p p p p p p hester et al.(24) p * p p * * p martin et al. (19) p p p p p p p yoo et al. (11) * * * * * p p franklin et al. (25) * p p p * * p staib et al. (26) * * p * * p p hertzum et al. (27) p * p * p * p mazor et al. (28) * * p * p * p mcgeorge et al. (29) * p * * p * p dexheimer et al. (30) * p * p * * p mcleod et al. (31) p * p p * p p bisantz et al. (32) p * * p * * p patterson et al. (33) p p p p p p p rasmussen et al. (34) * p * * * p p aronsky et al. (35) p p p * p * p pennathur et al. (36) p * p * p * p france et al. (37) * p p * p * p wears et al. (38) * p * p p * p boger (39) p p p * * p * 1. intervention independent of other changes 2. shape of the intervention effect pre-specified 3. intervention unlikely to affect data collection 4. knowledge of the allocated interventions adequately prevented during the study 5. incomplete outcome data adequately 6. selective outcome reporting 7. other risks of bias this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion and suggestion declarations references archives of academic emergency medicine. 2022; 10(1): e50 or i g i n a l re s e a rc h diagnostic accuracy of ultrasonography by emergency medicine resident in detecting intestinal obstruction; a pilot study anita sabzghabaei1, majid shojaei2, miromid chavoshzadeh1,3∗ 1. emergency department, shohadaye tajrish hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: march 2022; accepted: may 2022; published online: 26 june 2022 abstract: introduction: there are many ambiguities regarding the application of ultrasound in detection of intestinal obstruction. this study aimed to evaluate the diagnostic accuracy of ultrasound in diagnosis of intestinal obstruction. methods: this cross-sectional study was performed on patients with symptoms and signs of bowel obstruction between november 2019 and july 2020 in shohadaye-tajrish and imam hossein general hospitals, tehran, iran. after a brief explanation and getting verbal consent, the patients underwent ultrasound examination in the emergency department by the emergency medicine resident. the results of ultrasound were compared with the surgical findings as the gold standard. results: 24 patients with the mean age of 57.50±18.26 (range: 28 – 81) years were studied (58.3% male). ultrasonography findings revealed the lumen diameter ≥ 2.5 cm in 21 (87.5%) cases, wall thickness ≥ 3 mm in 3 (12.5%) cases and inter-loop free fluid in 3 (12.5%) cases. sensitivity, positive predictive value, and accuracy of ultrasound in detection of intestinal obstruction were found to be 85.00% (95%ci: 61.13 – 96.03), 80.95% (95%ci: 57.42 – 93.71), and 70.83% (95%ci: 48.91 – 87.38), respectively. conclusion: it seems that point-of-care ultrasound has good sensitivity and accuracy in detection of intestinal obstruction when performed in the emergency department by a trained emergency medicine resident. keywords: intestinal obstruction; point-of-care testing; ultrasonography; emergency service, hospital cite this article as: sabzghabaei a, shojaei m, chavoshzadeh m. diagnostic accuracy of ultrasonography by emergency medicine resident in detecting intestinal obstruction; a pilot study. arch acad emerg med. 2022; 10(1): e50. https://doi.org/10.22037/aaem.v10i1.1628. 1. introduction gastrointestinal obstruction is relatively a common problem requiring appropriate diagnostic and therapeutic interventions. this situation can occur anywhere along the gastrointestinal tract, and its clinical symptoms often vary based on the level of obstruction (1). intestinal obstruction is mostly due to intra-abdominal adhesions, malignancy, or intestinal hernias and its clinical manifestations generally include nausea and vomiting, colicky abdominal pain, and inability to pass stool or gas (2). the classic findings of physical examination, abdominal distention, tympanic sounds in percussion, and high-pitched intestinal sounds, might help ∗corresponding author: miromid chavoshzadeh; men’s health and reproductive health research center, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. email: omid.chavoshzadeh@gmail.com, tel: 00989121370587, orcid: https://orcid.org/0000-0002-7344-5890. to diagnose the disease in a timely manner; however, imaging modalities can confirm the diagnosis and be a useful adjunct in cases where the diagnosis is uncertain (3). in this regard, although the definitive diagnosis of bowel obstruction is made on clinical assessment followed by abdominal plain radiography or computed tomography (ct) scan, in many cases we encounter false negatives leading to failure in diagnosis as well as considerable complications (4). additionally, applying contrast-based modalities such as ct scan are frequently time-consuming, expensive, and intolerable for some patients and lead to radiation exposure (5). therefore, employing safe, available and cost-effective devices such as ultrasound have been recently considered for assessing intestinal obstruction. in some studies, this method has been shown to be more specific and sensitive than abdominal xray in confirming or ruling out intestinal obstruction in addition to determining the progression via repeated scans (6, 7). moreover, point-of-care ultrasound can help in finding this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sabzghabaei et al. 2 intestinal wall abnormalities such as interloop free fluid and thickened walls (8) or even deleterious problems like aortic dissection (9), which need prompt treatment. in addition, using doppler ultrasound can help assess the blood flow in intestinal wall and detect wall necrosis or differentiate benign or malignant lesions (10, 11). the availability of ultrasound in the emergency department, speed and ease of use, lower cost, and lack of ionizing radiation, have made it a desirable option for diagnosing small bowel obstruction (12-15). in addition to making the diagnosis of obstruction, ultrasound has been used to detect its etiology by some practitioners (16, 17). despite these studies, there are many ambiguities regarding the accuracy of ultrasonography in confirming or rejecting/ruling out obstruction and it is not yet used as standard practice. in this study, we aimed to evaluate the accuracy of ultrasound in diagnosis of intestinal obstruction. 2. methods 2.1. study design and setting this cross-sectional pilot study was performed on patients admitted to the emergency departments of shohadayetajrish and imam hossein hospitals, tehran, iran, with signs and symptoms of intestinal obstruction, between november 2019 and july 2020. after clarifying the possibility of intestinal obstruction, explanation of the ultrasound and the purpose of performing it, and obtaining oral consent, the patients underwent abdominal ultrasonography by the trained emergency medicine resident. then the findings of ultrasonography regarding intestinal obstruction were compared with surgery findings as the gold standard. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences (ethics code ir.sbmu.msp.rec.1398.216). 2.2. participants not giving consent, being referred with probable diagnosis of obstruction, bringing any imaging that suggests obstruction, hemodynamic instability, life threatening conditions, and not undergoing surgical treatment (as our gold standard of diagnosis) were considered as the exclusion criteria. 2.3. data gathering and procedure demographic findings (age, gender) as well as abdominal ultrasonography and surgery findings were collected using a predesigned checklist. a second-year emergency medicine resident (mc) underwent training by an emergency medicine associate professor, for four hours containing abdominal ultrasound of five patients. patients were evaluated with the ultrasound device honda hs-2100 in shohadaye-tajrish hospital and sonosite edge in imam hossein hospital by the same operator. using a low frequency (2.5-5 mhz) curvilinear probe, patients underwent ultrasound in supine position. the sweep like scan begins from the right iliac region, moves superiorly to right hypochondriac region, then epigastric region and goes downward to hypogastric region, and finally left iliac region to left hypochondriac region with the transducer in both cephalocaudal and transverse planes to cover the whole area of abdomen. since examining peristalsis needs a couple of minutes to be correctly done and there is limited time in the busy emergency department, it was not considered. when the diameter was more than 2.5 cm, and to ensure that a small bowel loop is scanned, we looked for plicae circularis, which is a characteristic feature of small bowel. evidence of small bowel obstruction was considered as intestinal lumen diameter more than 2.5 cm or wall thickness more than 3 mm or inter-loop free fluid (figure 1). the patients’ surgical technique was similar in all samples. 2.4. statistical analysis findings were presented as mean ± standard deviation (sd) for quantitative variables and frequency (percentage) for categorical variables. to determine the diagnostic value of ultrasound in diagnosis of intestinal obstruction compared to the gold standard (surgery), screening performance characteristics were calculated and presented with 95% confidence interval (ci). 3. results 24 patients with the mean age of 57.50±18.26 (range: 28 – 81) years were studied (58.3% male). ultrasonography findings revealed lumen diameter ≥ 2.5 cm in 21 (87.5%) cases, wall thickness ≥ 3 mm in 3 (12.5%) cases, and inter-loop free fluid in 3 (12.5%) cases. the sonographic evidence of small bowel obstruction was observed in 21 (87.5%) cases, while 17 (true positive) patients were confirmed to have obstruction in surgery (4 false positives). in three patients without ultra-sonographic evidence, obstruction was confirmed following surgery (false negative). four cases with false positive results had perforated gangrened appendix with extensive pelvic and retroperitoneal abscess, peritonitis due to cirrhosis and ascites, emphysematous pyelonephritis, and herniated abdominal wall. considering surgery as the gold standard for diagnosis of small bowel obstruction, sensitivity, positive predictive value, and accuracy of ultrasound in detection of intestinal obstruction were found to be 85.00% (95%ci: 61.13 – 96.03), 80.95% (95%ci: 57.42 – 93.71), and 70.83% (95%ci: 48.91 – 87.38), respectively (table 1). 4. discussion in recent years, with the widespread use of ultrasound in different fields of medicine, it has been used in the diagnosis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e50 figure 1: increased small bowel lumen diameter more than 2.5 cm (a); increased small bowel wall thickness more than 3 mm (b); inter-loop free fluid (c). table 1: screening performance characteristics of ultrasonography in detection of intestinal obstruction character value (%) 95% confidence interval lower limit (%) upper limit (%) sensitivity 85.00 61.13 96.03 specificity 0 0 60.42 positive predictive value 80.95 57.42 93.71 negative predictive value 0 0 69.00 positive likelihood ratio 4.25 1.717926 10.514134 negative likelihood ratio infinity nan infinity accuracy 70.83 48.91 87.38 nan: the calculation cannot be performed because the values entered include one or more instances of zero. of patients with suspected small intestine obstruction in several studies. because of the ease of use, low cost, high accessibility, and high accuracy reported in these studies, ultrasound has the potential to reduce many of the inherent limitations of traditional imaging. the use of ultrasound for a patient with suspected intestinal obstruction is convincing because of its potential to reduce the use of ct scans, being less expensive, limiting the use of contrast media, and reducing imaging time. the present study was performed to evaluate the diagnostic value of ultrasound in small bowel obstruction and the results showed that the sensitivity of ultrasound in diagnosis of small bowel obstruction was 85%. according to the results of this study, the positive predictive value for ultrasound was 80.95%, which means that if the test is positive in someone, they are 80.95% likely to have obstruction. the accuracy of ultrasound is also 70.8%, which means that ultrasound gives the correct answer in 70.8% of cases compared to the gold standard. in total, high diagnostic performance has been reported for ultrasound in detection of intestinal obstruction in previous studies. in a meta-analysis performed on 15 studies by lin et al. in 2021, the pooled sensitivity and specificity of ultrasound in detection of bowel obstruction were found to be 92% (95% ci: 89%-95%) and 93% (95% ci: 85%-97%), respectively (18). although sensitivity was similar in studies across different continents, specificity was lower in the north america, in the emergency department, and when computed tomography was used as the only reference standard. the different findings in our study could be the result of the ultrasound operator proficiency and the ultrasonography machine. in another meta-analysis by gottlieb et al. on 11 studies in 2018 (19), the pooled sensitivity and specificity of ultrasound was estimated to be 92.4% (95% ci 89.0% to 94.7%) and 96.6% (95% ci 88.4% to 99.1%), respectively. a meta-analysis conducted by taylor and lalani (20) to evaluate the method of choice for diagnosing small bowel obstruction in adults showed that ultrasound performed by an emergency physician had excellent diagnostic accuracy compared to other modalities, and was even superior to ctscan and mri. they also showed that ultrasound has the potential to play a greater role in diagnosis of small bowel obstruction in the emergency department. musoke and colleagues conducted a research in uganda in 2003, which compared the accuracy of ultrasound and abdominal radiography for diagnosing bowel obstruction (14). they reported 100% specificity, 93% sensitivity and accuracy, 100% ppv, and 73% npv. the reason for its high accuracy could be the age of patients, which were between 3 days to two years old, and the different main cause of obstruction, which was hernia (instead of adhesions). ultrasonography in jang and colleagues work (15) has higher sensitivity than our study, which can be due to comparing the ultrasound with ct-scan results as well as looking for both increased lumen diameter and decreased peristalsis. schmutz et al. found 91% accuracy when they excluded ‘gassy’ patients and 81% overall (17), which this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sabzghabaei et al. 4 might be because of the higher skills of radiologist operators. in general, different results could be related to the operators’ abilities, doing the ultrasound at the crowded emergency ward with less concentration and time, and not using the modality options like various probes and doppler, in addition to limited number of patients and their demographic characteristics. likewise, it should be noted that the accuracy of ultrasonography in diagnosis of intestinal obstructive lesions depends on various factors, including the experience of the operator performing the ultrasound scan, anatomical status, the level of obstruction, and patient cooperation. it is worth emphasizing that ultimately, the diagnosis of obstructive pathological lesions such as the etiology of obstruction will be possible based on surgery or biopsy, and imaging techniques are mainly auxiliary and screening tools for the disease. in addition, because of the increasing use of ultrasound in diagnostic and therapeutic procedures, especially in the emergency department, equipping these departments with advanced devices and improving users’ abilities in applying and interpreting ultrasound findings is recommended. 5. strengths and limitations the advantage of our study was comparing the results of ultrasound with surgery as the gold standard and performing point-of-care ultrasound by the emergency medicine resident. the major limitation of the present study was studying a limited number of patients. in fact, due to concurrence of the plan and the covid-19 pandemic, and since the venues were referral centers for covid-19 patients, the study could not be performed with a larger number of patients. also, due to the special conditions of the emergency department and its crowdedness, peristalsis, which is one of the indicators of small bowel obstruction in some studies, was not evaluated. 6. conclusion it seems that point-of-care ultrasound has good sensitivity and accuracy in detection of intestinal obstruction when performed in the emergency department by a trained emergency medicine resident. 7. declarations 7.1. acknowledgments we would like to thank all participants in the study and also sbmu emergency department mentors and residents. 7.2. authors’ contributions all authors meet the standard criteria of authorship contribution based on the recommendations of the international committee of medical journal editors. 7.3. funding and supports no funding was received for this study. 7.4. conflict of interest there is no conflict of interest in this study. references 1. catena f, de simone b, coccolini f, di saverio s, sartelli m, ansaloni l. bowel obstruction: a narrative review for all physicians. world j emerg surg. 2019;14(1):1-8. 2. jackson p, cruz mv. intestinal obstruction: evaluation and management. am fam physician. 2018;98(6):362-7. 3. pujahari ak. decision making in bowel obstruction: a review. j clin diagn res: jcdr. 2016;10(11):pe07. 4. denham g, smith t, james d, mckiernan s, evans t-j. exploring the evidence-practice gap in the use of plain radiography for acute abdominal pain and intestinal obstruction: a systematic review and meta-analysis. jbi evidence implementation. 2020;18(2):159-69. 5. li z, zhang l, liu x, yuan f, song b. diagnostic utility of ct for small bowel obstruction: systematic review and meta-analysis. plos one. 2019;14(12):e0226740. 6. rosano n, gallo l, mercogliano g, quassone p, picascia o, catalano m, et al. ultrasound of small bowel obstruction: a pictorial review. diagnostics. 2021;11(4):617. 7. tamburrini s, lugarà m, iaselli f, saturnino pp, liguori c, carbone r, et al. diagnostic accuracy of ultrasound in the diagnosis of small bowel obstruction. diagnostics. 2019;9(3):88. 8. tamburrini s, serra n, lugarà m, mercogliano g, liguori c, toro g, et al. ultrasound signs in the diagnosis and staging of small bowel obstruction. diagnostics. 2020;10(5):277. 9. rayat dost e, barazandehpour s, kalani n, abiri s. painless aortic dissection with slurred speech (neurologic symptom). journal of emergency practice and trauma. 2021;7(1):71-3. 10. wang mq, lee my, el teo h. ultrasound in the evaluation of necrotic bowel in children: a pictorial essay. ultrasound. 2019;27(4):207-16. 11. andrzejewska m, grzymisławski m. the role of intestinal ultrasound in diagnostics of bowel diseases. prz gastroenterol. 2018;13(1):1. 12. pourmand a, dimbil u, drake a, shokoohi h. the accuracy of point-of-care ultrasound in detecting small bowel obstruction in emergency department. emerg med int. 2018 apr 4;2018:3684081. doi: 10.1155/2018/3684081. pmid: 29850250; pmcid: pmc5904810. 13. ünlüer ee, yavasi ö, eroglu o, yilmaz c, akarca fk. ultrasonography by emergency medicine and radiology resithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e50 dents for the diagnosis of small bowel obstruction. eur j emerg med. 2010;17(5):260-4. 14. musoke f, kawooya m, miguli-malwadde e. comparison between sonographic and plain radiography in the diagnosis of small bowel obstruction at mulago hospital, uganda. east afr med j 2003;80(10):540-5. 15. jang tb, schindler d, kaji ah. bedside ultrasonography for the detection of small bowel obstruction in the emergency department. emerg med j. 2011;28(8):676-8. 16. ko yt, lim jh, lee dh, lee hw, lim jw. small bowel obstruction: sonographic evaluation. radiology. 1993;188(3):649-53. 17. schmutz g, benko a, fournier l, peron j, morel e, chiche l. small bowel obstruction: role and contribution of sonography. eur radiol. 1997;7(7):1054-8. 18. lin y-c, yu y-c, huang y-t, wu y-y, wang t-c, huang w-c, et al. diagnostic accuracy of ultrasound for small bowel obstruction: a systematic review and metaanalysis. eur j radiol. 2021;136:109565. 19. gottlieb m, peksa gd, pandurangadu av, nakitende d, takhar s, seethala rr. utilization of ultrasound for the evaluation of small bowel obstruction: a systematic review and meta-analysis. am j emerg med. 2018;36(2):234-42. 20. taylor mr, lalani n. adult small bowel obstruction. acad emerg med. 2013;20(6):527-44. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strengths and limitations conclusion declarations references emergency. 2017; 5 (1): e28 or i g i n a l re s e a rc h role of feedback during evaluation in improving emergency medicine residents’ skills; an experimental study ali vafaei1, kamran heidari1, mohammad-ali hosseini2, mostafa alavi-moghaddam3∗ 1. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. rehabilitation management department, university of social welfare and rehabilitation sciences, tehran, iran. 3. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: october 2016; accepted: november 2016; published online: 10 january 2017 abstract: introduction: evaluation of students’ learning in clinical education system is one of the most important and challenging issues that facilities in this field have been facing. the present study aimed to evaluate the role of feedback during evaluation in increasing emergency medicine residents’ clinical skills. method: the present experimental study was performed on all second year emergency medicine residents of two educational hospitals, tehran, iran, with switching replications design and before-after method. they were randomly divided to two groups (with or without feedback) and evaluated three times regarding chest ultrasonography for trauma patients, using direct observation of procedural skills (dops) and valid and reliable checklist. data were analyzed using spss 20. results: 30 emergency medicine residents with the mean age of 36.63 ± 30.30 years were devided to two equal groups (56.7% male). studied groups were similar regarding the baseline characteristics. in both groups, obtained scores showed a significant increase from the first to the third evaluation (p < 0.001). mean scores of first and second evaluations were 10.24 ± 0.77, 17.73 ± 0.46 in feedback receivers and 9.73 ± 0.77 and 12.13 ± 0.47 in others (p < 0.001). mean third evaluation scores after switching replication were 18.53 ± 0.22 in feedback receivers and 18.99 ± 0.22 in others (p = 0.213). conclusion: based on the findings of the present study, giving feedback after evaluating the second year emergency medicine residents regarding chest ultrasonography for trauma patients, led to a significant improvement in their scores in future evaluations and consequently their skill. keywords: education, medical, graduate; emergency medicine; learning; formative feedback © copyright (2017) shahid beheshti university of medical sciences cite this article as: vafaei a, heidari k, hosseini ma, alavi-moghaddam m. role of feedback during evaluation in improving emergency medicine residents’ skills; an experimental study. emergency. 2017; 5 (1): e28. 1. introduction training of clinical skills is one of the essential parts of medical education. medical education facilities have been developed for creating measurable changes in clinical practice (1). evaluation of students’ learning in clinical education system is one of the most important and challenging issues that facilities in this field have been facing (2). in most clinical courses, evaluation methods do not have sufficient efficiency for assessment of clinical skills (3-5). common evaluation methods have failed to assess students’ clinical skills accu∗corresponding author: mostafa alavi-moghaddam; emergency department, imam hossein hospital, shahid madani street, imam hossein square, tehran, iran. tel: +989122967248 e-mail: mosalavi@yahoo.com rately, they are not considered as tools for learning. to solve prominent problems, possible strengths and weaknesses of educational facilities were counted and then positive aspects of the educational facilities were improved and their shortcomings were eradicated (6). investigators in medical education field assessed some methods of clinical evaluation such as performance observation, 360 degree evaluation, objective structured clinical examination, mini-clinical evaluation exercise (mini-cex) and direct observation of procedural skills (dops), which have been used for evaluation of medical students and their clinical environments. effective assessment of medical students’ clinical skills can improve their motivation and help professors have a more accurate measurement of their actual skills (7). dops is known as a new procedure for evaluation of clinical practice skills of medical residents and students, which provides a suitable this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 2 feedback tool for medical professors (2). use of formative feedback has positive effects on professional behavior, attitude and communication for medical students (8). emergency department is one of the critical hospital wards in which residents must have clinical skills to be prepared for primary health care procedures, diagnosis and treatment of referred patients. based on the above-mentioned points, the present study aimed to evaluate the role of feedback during evaluation in increasing emergency medicine residents’ clinical skills. 2. methods 2.1. study design and setting the present experimental study was performed on all second year emergency medicine residents of two educational hospitals affiliated with shahid beheshti university of medical sciences (imam hossein and loghman hakim), tehran, iran, from june to november 2015, with switching replications design and before-after method. the study aimed to evaluate the role of feedback during evaluation (fde) in increasing residents’ skills regarding chest ultrasonography for trauma patients. all researchers adhered to ethical recommendations of helsinki protocol and confidentiality of participants’ information during the study period. 2.2. ethical consideration individuals participated in the study by giving informed consent, in addition, data were analyzed as a pool, and the name of individuals was not mentioned. the researchers promised to share the results with the participants on demand. all the patients that participated in rating the skills of residents were selected based on the indications provided in references and were given sufficient information regarding the method of the study. any patient that wanted to leave the study or the hospital was excluded from the study. replacements were selected for the 8 patients that decided to leave the study or the hospital. this study did not interfere with the routine diagnostic and treatment process of the patients or impose additional costs on them. 2.3. participants study participants were selected from second year emergency medicine residents, who had passed their first year promotion exam, using census sampling. all participants were trained regarding chest ultrasonography for trauma patients during their first year of the residency program. they were randomly divided into 2 groups of loghman hakim (group 1) or imam hossein hospital (group 2), using simple randomization method. in each studied hospital, one emergency medicine professor, who was informed regarding the study design and dops method, was responsible for evaluation of residents. both attends, who were responsible for evaluation of the participants, were informed regarding the method of the study and its details in a 4-hour coordinator session. 2.4. procedure after preparing essential tools for doing the procedure, participants were evaluated regarding chest ultrasonography for blunt trauma patients using dops method. initially, all the participants (separately in both study hospitals) were evaluated using a checklist designed for this purpose and dops method in off-duty hours and their scores were recorded. at this stage, after the evaluation was finished, the residents in loghman hakim hospital were given feedback on their weak and strong points for 5 minutes but those in imam hossein hospital were evaluated traditionally and without feedback. after 2 months, the evaluation was repeated for residents of both hospitals. however, this time evaluation method was switched between the 2 groups and this time residents of imam hossein hospital were given feedback and those in loghman hakim hospital took were evaluated traditionally and without feedback. finally, about 2 months later, all the second year residents of both hospitals were evaluated again, for the third time. duration of evaluation was 15 minutes in all 3 stages, and when the residents were supposed to receive feedbacks it would be organized in 5 minutes. effort was made to provide similar environmental conditions such as time, place, ultrasonography device, evaluated patients, etc. for both groups. 2.5. data gathering data gathering tool was a standard (20-item) checklist prepared according to evidence-based texts regarding the requirements that should be met in this procedure (appendix 1). items of the checklist were designed to evaluate 3 general parts of the procedure including preparation (4 items), carrying out the procedure (13 items), and post-procedure measures (3 items). each correct answer was given 1 point and for wrong answers, no point was given. consequently, the maximum and minimum obtainable scores for each participant were 20 and 0, respectively. a score between 0 and 10 was considered as fail and a score between 10 and 20 was considered as pass. score above 17 was classified as an excellent score. validity of the prepared checklist was approved by 10 emergency medicine professors with more than 5 years of experience from various universities. reliability of the tools was calculated in a pilot study on 15 people and its correlation coefficient was estimated to be 85% based on cronbach’s alpha. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e28 appendix 1: evaluation checklist of chest ultrasonography for trauma patients using dops method items proper performance points* preparation yes no 1. correctly identifying the patient 2. introducing self and being professional 3. knowing indications of the procedure 4. proper position of patient and device ultrasonography performance 1. preparing proper tools 2. correct selection of probe 3. evaluation regarding pneumothorax 4. identifying and evaluating the 3 zones 5. evaluating all intercostal spaces 6. identification of pleural cavity 7. lung point sign evaluation 8. pleural sliding evaluation 9. evaluation of comet tails/b-line 10. evaluation of seashore sign in m-mode 11. evaluation regarding hemothorax 12. right side evaluation of hemothorax 13. left side evaluation of hemothorax post-procedure 1. saving and printing the image 2. interpretation of findings 3. proper decision based on findings *: each right answer gets 1 point and wrong answers receive no point (minimum 0 and maximum 20). 2.6. statistical analysis study variables were analyzed by spss software version 20. mean ± standard deviation or frequency and percentage were used for quantitative and qualitative variables, respectively. paired sample t-test and chi-square were used for comparing quantitative and qualitative variables between study groups. the greenhouse-geisser correction test was used for assessing the impact of repeatedly performing dops. all p-values less than 0.05 were considered as significant. 3. results: 3.1. baseline characteristics 30 emergency medicine residents with the mean age of 36.63 ± 30.30 (29 47) years participated (56.7% male). they were randomly allocated to either loghman hakim (group 1) or imam hossein hospitals (group 2). table 1 shows the baseline characteristics of the participants. the two studied groups were similar regarding the baseline characteristics. 25 (83.4%) residents performed chest ultrasonography more than five times (56.7% more than 10 times) and 25 (83.3%) residents believed that chest ultrasonography for trauma patients had medium to high difficulty level. figure 1: trend of scores (minimum 0 and maximum 20) in three evaluations of studied groups (p < 0.001, based on greenhousegeisser correction). 3.2. outcomes mean scores of the residents in the first, second, and third evaluations were 10.00 ± 0.54, 14.93 ± 0.32, and 18.72 ± 0.15, respectively. figure 1 shows the scores obtained by the residents for the 3 evaluations done based on the hospital. in both groups, obtained scores showed a significant increase from the first to the third evaluation (p < 0.001) according to greenhouse-geisser correction test. mean score obtained for preparation, scan and post-scan items among all resithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 4 table 1: baseline characteristics of participants variable loghman hakim imam hossein p mean age (year) 34.93 ± 5.40 38.33 ± 5.23 0.091 sex male 9 (60) 8 (53.3) 0.71 female 6 (40) 7 (46.7) previous experience1 (time) 1 -4 3 (20) 2 (13.3) 59 4 (26.7) 4 (26.7) 0.879 ≥ 10 8 (53.3) 9 (60) background attitude2 (difficulty) low 4 (26.7) 1 (6.7) medium 10 (66.7) 11 (73.3) 0.241 high 1 (6.7) 3 (20) mean promotion exam score3 81.06 ± 6.29 82.42 ± 6.27 0.565 data were presented as mean ± standard deviation or frequency (percentage); 1: previous experience of chest ultrasonography; 2: attitude of the resident regarding the difficulty of the procedure; 3: score in exam taken for promotion from year 1 to year 2 of the residency program (out of 100). table 2: comparison of mean evaluation scores between groups evaluation loghman hakim imam hossein p-value preparation (0 4) first 3.00 ± 0.75 2.1 ± 0.92 0.009 second 4.00 ± 0.00 3.00 ± 0.85 < 0.0001 third 3.93 ± 0.26 4.00 ± 0.00 0.326 scan (0 13) first 6.87 ± 2.39 6.27 ± 2.43 0.501 second 11.60 ± 0.99 7.33 ± 1.95 < 0.001 third 12.53 ± 0.74 12.26 ± 0.59 0.287 post scan (0 3) first 0.40 ± 0.63 1.20 ± 0.67 0.002 second 2.13 ± 0.35 1.80 ± 0.86 0.176 third 2.53 ± 0.64 2.27 ± 0.71 0.287 total (0 20) first 10.26 ± 2.99 9.73 ± 2.94 0.626 second 17.73 ± 1.09 12.13 ± 2.29 <0.001 third 18.93 ± 0.96 18.53 ± 0.74 0.213 data were presented as mean ± standard deviation. table 3: comparison of score quality between groups evaluation loghman hakim imam hossein p-value first failed 8 (53.3) 5 (33.3) passed 7 (46.7) 10 (66.7) 0.462 excellent 0 (0) 0 (0) second failed 0 (0) 2 (13.3) passed 3 (20) 13 (86.7) < 0.001 excellent 12 (80) 0 (0) third failed 0 (0) 0 (0) passed 15 (100) 15 (100) na excellent 0 (0) 0 (0) data were presented as frequency and percentage; na: not applicable. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e28 dents were 3.34 ± 0.91, 9.48 ± 3.16, and 1.72 ± 0.97, respectively. tables 2 and 3 compare the scores obtained by each group in the 3 tests qualitatively and quantitatively. mean scores of first and second evaluations were 10.24 ± 0.77, 17.73 ± 0.46 in feedback receivers and 9.73 ± 0.77 and 12.13 ± 0.47 in others (p < 0.001). mean third score after switching groups were 18.53 ± 0.22 in feedback receivers and 18.99 ± 0.22 in others (p = 0.213). as can be seen, residents in loghman hakim hospital were significantly better in the second exam both quantitatively and qualitatively. 4. discussion: based on the findings of the present study, giving feedback after evaluating the second year emergency medicine residents regarding chest ultrasonography for trauma patients, led to a significant improvement in their scores in future evaluations and consequently their skill. previous studies have shown that assessment of trainees via dops can significantly improve skill learning among medical students and residents in some countries (9-11). in most medical education curriculums, dops was used for evaluation of main clinical skills such as intravenous cannulation, lumbar puncture, and endotracheal intubation. these procedures were observed in different clinical settings including outpatient clinics and emergency departments. barton et al. and thomas-gibson et al. studies indicated that dops method causes an increase in residents’ competence in the fields of colonoscopy and endoscopy (12, 13). according to the findings of hauck s et al., use of dops for medical students in ultrasound training field caused a significant increase in their knowledge, confidence, self-motivation and understanding of anatomical structures. it is recommended that medical trainers observe medical students while doing the procedure on the patients, and ask them about indications, complications and post procedure cares and immediately give them feedback for future improvement of their skills. charleen liu, who is active in the emergency medicine training field in the united kingdom, believes that the recent trend in medical education is rapidly moving from traditional routine examinations to collecting evidence of clinical competence and professional behavior observed in clinical environments (work-based learning) through methods such as dops, mini-cex, and casebased discussion (cbd). this is consistent with the highest level of the miller education pyramid (14). it is believed that some factors in dops such as more practice in implementation of procedure, evaluations in several stages, and giving feedback in each stage can explain improvement of clinical skill among study participants. based on these results of holmboe et al., dops leads to significant changes in students’ behavior and competence improvement, as well as increase of teachers’ confidence and satisfaction compared to traditional methods (15, 16). the results of the current study revealed the significant effect of giving feedback during educational evaluation. scores of the second evaluation was significantly higher both qualitatively and quantitatively in the group that had received feedback regarding their strong and weak points compared to those who had not. however, after switching the method of evaluation in the second phase, the scores of both groups were at the same level in the third evaluation. among the secondary outcomes of the study was that it seems that regular evaluation using dops itself can improve the skill score of the residents. 5. limitations among the limitations of the present study are the small sample size and evaluation of the residents by 2 separate attends. in addition, considering the previous familiarity of attends with residents we cannot be sure if a conflict of interest existed in their scoring or not. however, in this regard all efforts were made to minimize these limitations by randomly dividing the residents and giving explanations to the evaluators. 6. conclusion: based on the findings of the present study, giving feedback after evaluating the second year emergency medicine residents regarding chest ultrasonography for trauma patients, led to a significant improvement in their scores in future evaluations and consequently their skill. 7. appendix 7.1. acknowledgements the authors would like to thank all the staff of medical education faculty of shahid beheshti university of medical sciences and clinical research development center of loghman hakim hospital for their cooperation. 7.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. abedini sas, aghamolaee t, jome zadeh a, kamjo a. clinical education problems from the perspective of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 6 nursing and midwifery students hormozgan university of medical sciences. journal of hormozgan university ofmedical sciences. 2009;12:249-53. 2. crossley j, humphris g, jolly b. assessing health professionals. medical education. 2002;36(9):800-4. 3. nouhi sfa, foroud a, editors. investigation of the problems in clinical evaluation according to clinical teachers of medicine and dentists in kerman university of medical sciences 6th medical 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from: www.jemerg.com introduction methods results: discussion: limitations conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e18 https://doi.org/10.22037/aaem.v9i1.1071 rev i ew art i c l e cardiac complications and pertaining mortality rate in covid-19 patients; a systematic review and metaanalysis amirmohammad toloui1, donya moshrefiaraghi1, arian madani neishaboori1, mahmoud yousefifard1∗, mohammad haji aghajani2 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. received: december 2020; accepted: january 2021; published online: 13 february 2021 abstract: introduction: raising knowledge over cardiac complications and managing them can play a key role in their recovery. in this study, we aim to investigate the evidence regarding the prevalence of cardiac complications and the resulting mortality rate in covid-19 patients. methods: search was conducted in electronic databases of medline (using pubmed), embase, scopus, and web of science, in addition to the manual search in preprint databases, and google and google scholar search engines, for articles published from 2019 until april 30th, 2020. inclusion criterion was reviewing and reporting cardiac complications in patients with confirmed covid19. results: the initial search resulted in 853 records, out of which 40 articles were included. overall analysis showed that the prevalence of acute cardiac injury, heart failure and cardiac arrest were 19.46% (95% ci: 18.2320.72), 19.07% (95% ci: 15.38-23.04) and 3.44% (95% ci: 3.08-3.82), respectively. moreover, abnormal serum troponin level was observed in 22.86% (95% ci: 21.19-24.56) of the covid-19 patients. further analysis revealed that the overall odds of mortality is 14.24 (95% ci: 8.67-23.38) times higher when patients develop acute cardiac injury. the pooled odds ratio of mortality when the analysis was limited to abnormal serum troponin level was 19.03 (95% ci: 11.85-30.56). conclusion: acute cardiac injury and abnormal serum troponin level were the most prevalent cardiac complications/abnormalities in covid-19 patients. the importance of cardiac complications is emphasized due to the higher mortality rate among patients with these complications. thus, troponin screenings and cardiac evaluations are recommended to be performed in routine patient assessments. keywords: covid-19; cardiovascular system; heart injuries; hospital mortality cite this article as: toloui a, moshrefiaraghi d, madani neishaboori a, yousefifard m, haji aghajani m. cardiac complications and pertaining mortality rate in covid-19 patients; a systematic review and meta-analysis. arch acad emerg med. 2021; 9(1): e18. 1. introduction severe acute respiratory syndrome coronavirus 2 (sars-cov2) is a novel coronavirus, which emerged in wuhan, china in december 2019 and has spread to over 200 countries in the world, ever since (1). coronavirus disease 2019 (covid19) mostly causes lower respiratory tract infection symptoms such as fever, which is its most prevalent symptom, cough, ∗corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; e-mail: yousefifard.m@iums.ac.ir † corresponding author: mohammad haji aghajani; imam hossein hospital, madani st., tehran, iran; phone/fax: +982173432383/77582733; e-mail: dr.aghajani@yahoo.com and dyspnea (2). although people with severe type of the disease form the minority of the patients, it is illustrated that mortality rate is the highest among patients who have comorbidities such as cardiovascular diseases (3). angiotensin converting enzyme 2 (ace2) has been shown to be the receptor of the virus in human cells. since this enzyme is expressed in many organs such as lungs, heart, kidneys and brain, extrapulmonary manifestations and complications are being studied rigorously, all around the world (4). cardiac involvement is one of the most common causes of death in covid-19 patients (5). cardiovascular complications, whether being chronic or acute, can lead to critically imbalanced homeostasis and could be a serious strike to patient’s recovery from the disease (6). therefore, raising awareness over cardiac complications caused by the disease this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 2 and managing them as early as possible can play a key role in recovery of the patients. however, there is no comprehensive evaluation of this issue. therefore, in this study, we aim to investigate the evidence regarding the prevalence of cardiac complications in covid-19 patients. moreover, the risk of mortality after covid-19 related cardiac involvement has also been assessed. 2. methods 2.1. study design the present systematic review and meta-analysis aims to investigate the evidence regarding cardiac complications in patients, confirmed with covid-19, and to see whether there is any potential association between the prevalence of cardiac complications and their mortality rate. as a result, peco in the current study is defined as: p (patients): patients with confirmed covid-19 disease, e (exposure): sars-cov-2 infection, o (outcome): prevalence of cardiac complications and mortality after covid-19 related cardiac involvement. as for comparison (c in peco), mortality rate was compared between covid-19 patients with cardiac complications and patients without any cardiac involvements. 2.2. search strategy the searching process was initiated by selecting keywords with the help of experts in the field and screening titles of similar articles. then, using mesh and emtree, equivalent and related synonyms were identified. as a result, a search strategy was constructed based on the instructions of electronic databases of medline, embase, scopus, and web of science, and an extensive search was performed in each of the mentioned databases for articles published from the february 1st of 2019 until april 30th, 2020. the search strategy in medline database through pubmed search engine is presented in appendix 1. in addition, a search was performed in preprint databases, google, and google scholar to obtain preprinted and possibly missed manuscripts (gray litterateur search). moreover, references of the obtained review articles were screened to find additional articles. 2.3. selection criteria the inclusion criteria in the present meta-analysis was reporting cardiac complications and cardiac related mortality rate in patients with confirmed covid-19. original observational studies were included. since most covid-19 studies had a retrospective nature, both retrospective and prospective studies were included. prevalence of cardiac complications following covid-19 and its pertaining mortality rate were extracted from cohort and cross-sectional studies. in addition, we added an extra aim to provide evidence on the relationship between cardiac complication occurrence in covid-19 patients and their mortality. in this section, in addition to cohort and cross-sectional studies, case-control studies were also included. furthermore, the exclusion criteria were case report studies, review articles, studies that did not report cardiac involvement and studies whose entire target population was patients with cardiac comorbidities as underlying disease. 2.4. data collection two independent reviewers screened titles and abstracts of the gathered articles. then, full texts of the related articles were obtained and included articles were selected and entered the present systematic review and meta-analysis. finally, a summary of the included studies was recorded using a checklist, consisting of following variables: first author’s name, publication year, country in which the study was conducted in, number of patients, study design, number of patients in which the cardiac complication was assessed in, mean/median age of the patients, number of males among the patients, type of cardiac complication along with its diagnostic method, number of the deceased in patients presenting with cardiac complication (if reported), and number of the deceased among patients without the cardiac complication of the included articles. if several types of cardiac complications were reported in the studies, the number of each cardiac involvement was recorded separately. any disagreements within the process were resolved using a third reviewer’s opinion. 2.5. outcome the primary outcome of the present meta-analysis was the prevalence of cardiac complications in covid-19 patients. secondary outcome was the risk of mortality after covid-19 related cardiac involvement. our screening showed that most studies reported abnormal serum troponin level and acute cardiac injury, separately, as cardiac assessments/complications. other reported cardiac complications were heart failure, cardiomyopathy, cardiac arrest, myocarditis, pericardial effusion, cardiac insufficiency, and myocardial infarction. 2.6. quality assessment two independent reviewers scored the quality of the studies according to national heart, lung, and blood institute (nhlbi) quality assessment tool (7). this tool contains 14 items on study design, patient selection, sample size justification, analysis, timeframe between exposure and outcome, assessment of different level of exposure, validity and reliability of exposure and outcome assessment, blinding status, missing data management, and considering potential confounders in the analysis. each reviewer independently assessed the articles and categorized each item as low risk, high this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e18 risk, unclear risk of bias, cannot determine, or not applicable. any disagreement was resolved by discussion with a third reviewer. 2.7. statistical analysis all analyses were performed using stata 14.0 statistical program. analyses were performed in two parts. initially, the cardiac complications reported in the articles were categorized into 9 subgroups: acute cardiac injury, abnormal serum troponin level, heart failure, cardiac arrest, myocarditis, cardiac insufficiency, pericardial effusion, myocardial infarction, and cardiomyopathy. the prevalence of each cardiac complication among the covid-19 patients was calculated with a 95% confidence interval (95% ci) using the “metaprop_one” command performed on the total sample size and the number of patients presenting each complication in the included articles. in the second part of the analysis, the association between the manifestation of cardiac complications/abnormalities and mortality rate was calculated and presented as an overall odds ratio (or) with a 95% ci using the “metan” command performed on four groups of data: number of the deceased in patients with a cardiac complication, number of the alive in patients with the cardiac complication, number of the deceased in patients without the cardiac complication, number of the alive in patients without the cardiac complication. i2 test was performed to assess heterogeneity, and if the heterogeneity among data was considerable, random effect model was used to calculate 95% ci. egger’s test was used to evaluate publication bias. finally, a sensitivity analysis was performed to determine whether the results can be considered robust or not. therefore, in the sensitivity analyses we excluded possible outlier studies. 3. results 3.1. study characteristics the systematic search resulted in 853 records, and after eliminating duplicates, 557 articles remained. then, after screening titles and abstracts of the remaining articles, 181 studies were deemed potentially eligible. afterwards, based on the mentioned exclusion and inclusion criteria, 40 articles were included in the present systematic review and meta-analysis (figure 1) (5, 8-46). these 40 articles were treated as 60 different experiments, as some studies reported more than one cardiac complication/abnormality. two studies had taken place in the united states (41, 45), one study was conducted in spain (9), one study was carried out in italy (42) and the rest of the included studies were conducted in china. regarding the study design of the included articles, one study was ambispective (22), four studies were conducted prospectively (9, 14, 19, 39) and the other 35 studies were retrospective. overall, 15616 patients with confirmed covid-19 were enrolled in the included studies, with 2985 males among them [patients’ gender was not reported in two of the studies (42, 46)]; however, not all of the patients were assessed for each cardiac complication, so the total number of patients tested for each manifestation is presented for each complication in table 1. in general, 9 different cardiac complications/abnormalities were reported in the studies including acute cardiac injury, which was reported in 26 studies (5, 8, 11, 13, 16, 18-20, 22-24, 26-30, 32, 33, 35, 37-41, 43, 46), abnormal serum troponin level, reported in 19 studies (8, 10-12, 14, 15, 17, 19, 25, 30, 32, 36-38, 40, 41, 43-45), heart failure, reported in four studies (8, 11, 32, 41), cardiac arrest, reported in three studies (5, 34, 42), myocarditis, reported in two studies (9, 44), cardiac insufficiency, reported in two studies (29, 30), pericardial effusion, reported in two studies (21, 31) and cardiomyopathy (45) and myocardial infarction (32), each reported in one study. mortality rate was reported in 18 studies (8, 11, 13, 14, 16-18, 20, 26, 29, 30, 33, 34, 37, 39, 40, 44, 46). these numbers were further used to evaluate the odds ratio (or) between the manifestation of each cardiac complication and the mortality rate in covid-19 patients. table 1 demonstrates a summary of the characteristics of the included studies. 3.2. risk of bias assessment no study had provided a sample size justification, power description, or variance and effect estimates. in addition, 39 studies were not measured to have key potential confounders in their assessment of outcomes. 10 studies did not report the details of their inclusion and exclusion criteria. moreover, the participation rate of eligible persons was not reported in 6 studies (table 2). 3.3. publication bias there were evidences of publication bias in the assessment of the prevalence of acute cardiac injury (coefficient= -3.97; p=0.004) and abnormal serum troponin level (coefficient = -8.65; p < 0.001) among the included studies. however, no evidence of publication bias was observed in the assessment of cardiac related mortality and the prevalence of other cardiac complications (figure 2). 3.4. meta-analysis in the beginning, the prevalence of cardiac complications following sars-cov-2 infection was evaluated, and the results are depicted in figures 3, 4, 5 and 6, and table 3. abnormal serum level of troponin was observed in 22.86% (95% ci: 21.19 to 24.56) of the patients (figure 4). moreover, the prevalence of acute cardiac injury, heart failure and cardiac arrest was 19.46% (95% ci: 18.23 to 20.72), 19.07% (95% ci: 15.38 to 23.04) and 3.44% (95% ci: 3.08 to 3.82), respectively (figure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 4 3 and table 3). furthermore, the i2 test revealed no heterogeneity regarding the prevalence of abnormal troponin levels and acute cardiac injury. the prevalence of other cardiac complications including myocarditis, cardiac insufficiency, pericardial effusion, myocardial infarction, and cardiomyopathy are depicted in table 3. sensitivity analysis showed that after excluding the studies with a high prevalence rate, the prevalence of abnormal serum level of troponin (20.16%; 95% ci: 18.54 to 21.82; cut off for high prevalence rate=50%) and acute cardiac injury (17.17%; 95% ci: 15.94 to 18.43; cut off for high prevalence rate=30) decreased slightly. further analysis revealed that the odds of mortality in covid-19 patients with acute cardiac injury is 14.24 (or = 14.24, 95% ci: 8.67 to 23.38) times higher than the covid19 patients without acute cardiac injury. however, i2 test showed some degrees of heterogeneity regarding the relationship of cardiac complication and mortality of covid19 patients (figure 5). there is a possible outlier study in acute cardiac injury section. after excluding this study, the odds of mortality in covid-19 patients with acute cardiac injury is increased slightly (or=15.77; 95% ci: 10.49 to 23.69). in the sensitivity analysis the heterogeneity was decreased (i2=45.5%). moreover, the odds of mortality in a covid-19 patient presenting with abnormal serum troponin level in his/her blood sample was 19.03 (or=19.03; 95% ci: 11.85 to 30.56) times higher than the patients not having this manifestation. interestingly, no heterogeneity was observed when calculating the or for the mortality in covid-19 patients with abnormal serum troponin level (figure 6). there are two possible outlier studies in abnormal troponin level section. after excluding these studies, the odds of mortality in covid-19 patients with acute cardiac injury is increased slightly (or=17.07; 95% ci: 10.41 to 27.99). the odds of mortality of patients having other cardiac complications are presented in table 3. 4. discussion in this systematic review and meta-analysis, we investigated the prevalence of 9 cardiac complications in covid-19 patients and their subsequent mortality rates. abnormal serum level of troponin with 22.86% prevalence, detected by laboratory tests, and acute cardiac injury with 19.46% prevalence, diagnosed with laboratory test results and other diagnostic techniques, were among the most prevalent complications/abnormalities observed in covid-19 patients. although a large number of studies reported the prevalence of the two mentioned cardiac complications, no heterogeneity was observed in this section. to contemplate even more on the matter, the prevalence of abnormal troponin level and acute cardiac injury are rather close numbers, which might mean that by close observation of troponin changes in a covid-19 patient, we could possibly anticipate acute cardiac injuries in them and take appropriate measures. however, serum troponin levels also increase due to damage to other tissues, such as the kidneys, which may make it impossible to use troponin level alone to detect cardiac damage. other cardiac complications such as heart failure and cardiomyopathy were also prevalent among the patients. however, with the small number of the studies observing them, more data is needed on the matter. regarding the limitations, each individual article used a different reference range for troponin or other injury indicators to be classified as abnormal, and each one used different diagnostic and laboratory test results to define acute cardiac injury, which could cause slight differences in the reported prevalence of acute cardiac injury and abnormal serum level of troponin. for example, huang et al. defined acute cardiac injury as cardiac troponin rising to 3 or more times than normal or appearance of new abnormalities in echocardiography or ecg (19); while many others defined it only with the appearance of abnormal troponin levels in blood samples. moreover, some articles’ study population only consisted of critically ill patients or deceased ones, which could shift prevalence statistics, causing inevitable heterogeneity in reported numbers (5, 15, 32). additionally, it is worth mentioning that the mechanism of myocardial injury, whether being done by direct viral invasion to the host tissue or due to imbalanced homeostasis, was of no concern for the writers at the time. although more research should be conducted to identify the exact causes of this damage, the effects it carries are the most important subject that should be studied at these critical times. even though limitations were present in data reporting the prevalence of cardiac outcomes, it is important to pay enough attention to these complications, since many of them are directly related to patients’ general situation and illness severity. on the other hand, our study shows intriguing data regarding mortality rate in patients presenting with cardiac complications, especially acute cardiac injury and abnormal serum level of troponin. abnormal troponin levels are associated with about 19 times higher mortality risk in covid-19 patients, which is of great importance in disease management for health care providers around the world. considering the fact that no heterogeneity was observed regarding the risk of mortality in patients with abnormal troponin level, laboratory screening during routine patient assessments can be critical in early detection of cardiac injury and intervening accordingly. in addition, we suggest that blood levels of troponin should be evaluated as a prognostic factor in patients with cardiac involvement. furthermore, our data indicated that acute cardiac injury could raise the mortality to about 14 times more in covid19 patients. however, this number was associated with an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e18 overall heterogeneity, which could be attributed to different definitions of cardiac injury in studies, discussed above. nonetheless, although one can conclude that there is a relationship between acute cardiac injury following covid19 and increased risk of mortality, the threat that acute cardiac injury poses to patients’ health status in the future is undeniable and demands careful monitoring and managements when confronting this situation. moreover, it is noteworthy that articles reporting mortality rates of cardiac complications were mostly focused on abnormal troponin level and myocardial injury and the number of the articles reporting correlations between other cardiac complications such as heart failure, and mortality rate was very few; so, we cannot present an exact estimation of the contribution of other cardiac outcomes such as heart failure and myocarditis to patients’ fatality. in addition, inability to blind the outcome assessors in the studies and some articles not explicitly presenting inclusion and exclusion criteria were further limitations detected in the studies. finally, we performed a sensitivity analysis and excluded possible outlier studies. the overall effect size slightly changed and therefore, the results seem to be robust. to conclude, our findings thoroughly approve of other published articles investigating associations between covid-19 cardiac outcomes and related mortalities (47, 48), confirming that cardiac injury, regardless of the mechanism of establishment, is a factor determining disease severity and patient prognosis reliably in large scale and should be considered and monitored from early stages of disease. 5. conclusion cardiac complications/abnormalities can be prevalent in covid-19 patients in the forms of acute cardiac injury, serum troponin levels abnormalities, heart failure, cardiac arrest, and other types. the importance of cardiac involvements is further highlighted when observing the higher mortality rate among covid-19 patients presenting with cardiac involvements. thus, careful monitoring of heart involvements should be performed in covid-19 patients. 6. abbreviations sars-cov-2: severe acute respiratory syndrome coronavirus 2 covid-19: coronavirus disease 2019 ace2: angiotensin converting enzyme 2 peco: problem, exposure, comparison, outcome nhlbi: national heart, lung, and blood institute ci: confidence interval or: odds ratio ecg: electrocardiography 7. declarations 7.1. ethics approval and consent to participate this study received ethics approval from ethics committee of iran university of medical sciences. 7.2. consent for publication not applicable. 7.3. availability of data and materials all data generated or analyzed during this study are included in this published article [and its supplementary information files]. 7.4. conflict of interest there is no conflict of interest. 7.5. funding this study was supported by prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 7.6. authors’ contribution study design: my, mha; data 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2020;20:1-8. 44. ma k-l, liu z-h, cao c-f, liu m-k, liao j, zou j-b, et al. covid-19 myocarditis and severity factors: an adult cohort study. medrxiv. 2020. 45. arentz m, yim e, klaff l, lokhandwala s, riedo fx, chong m, et al. characteristics and outcomes of 21 critically ill patients with covid-19 in washington state. jama. 2020;323(16):1612-4. 46. ruan q, yang k, wang w, jiang l, song j. clinical predictors of mortality due to covid-19 based on an analysis of data of 150 patients from wuhan, china. intensive care medicine. 2020;46(5):846-8. 47. zhu h, rhee j-w, cheng p, waliany s, chang a, witteles rm, et al. cardiovascular complications in patients with covid-19: consequences of viral toxicities and host immune response. current cardiology reports. 2020;22:1-9. 48. santoso a, pranata r, wibowo a, al-farabi mj, huang i, antariksa b. cardiac injury is associated with mortality and critically ill pneumonia in covid-19: a metaanalysis. the american journal of emergency medicine. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 8 appendix 1: medline search query search terms 1.“covid-19 “[supplementary concept] or ”severe acute respiratory syndrome coronavirus 2”[supplementary concept] or ”covid-19 vaccine”[supplementary concept] or ”covid-19 diagnostic testing”[supplementary concept] or ”covid-19 drug treatment”[supplementary concept] or “betacoronavirus”[mh] or “coronavirus infections”[mh] or covid-19[tiab] or 2019 novel coronavirus disease[tiab] or covid19[tiab] or covid-19 pandemic[tiab] or sars-cov-2 infection[tiab] or covid-19 virus disease[tiab] or 2019 novel coronavirus infection[tiab] or 2019-ncov infection[tiab] or coronavirus disease 2019[tiab] or coronavirus disease19[tiab] or 2019-ncov disease[tiab] or covid-19 virus infection[tiab] or severe acute respiratory syndrom coronavirus 2[tiab] or coronavirus[tiab] or coronaviruses[tiab] or severe acute respiratory syndrome coronavirus 2[tiab] or 2019-ncov[tiab] or wuhan coronavirus[tiab] or sars-cov-2[tiab] or 2019 novel coronavirus[tiab] or covid-19 virus[tiab] or coronavirus disease 2019 virus[tiab] or covid19 virus[tiab] or wuhan seafood market pneumonia virus[tiab] or betacoronavirus[tiab] or betacoronaviruses[tiab] or coronavirus infections[tiab] or coronavirus infection[tiab] or infection, coronavirus[tiab] or infections, coronavirus[tiab] or covid-19 vaccine[tiab] or covid-19 diagnostic testing[tiab] or covid-19 drug treatment[tiab] or coronavirus disease 2019 drug treatment[tiab] or covid-19 treatment[tiab] or treatment of covid-19 virus infection[tiab] or coronavirus disease19 drug treatment[tiab] 2.“troponin”[mh] or “heart injuries”[mh] or “myocarditis”[mh] or “cardiomyopathies”[mh] or “heart diseases”[mh] or “pericarditis”[mh] or “cardiovascular abnormalities”[mh] or “cardiovascular infections”[mh] or “cardiovascular diseases”[mh] or “heart arrest”[mh] or “ventricular dysfunction”[mh] or “heart failure”[mh] or “heart failure, diastolic”[mh] or “heart failure, systolic”[mh] or heart injuries[tiab] or [tiab] or injuries, heart[tiab] or heart injury[tiab] or injury, heart[tiab] or myocarditis[tiab] or myocarditides[tiab] or carditis[tiab] or cardiomyopathies[tiab] or cardiomyopathy[tiab] or myocardial diseases[tiab] or disease, myocardial[tiab] or diseases, myocardial[tiab] or myocardial disease[tiab] or myocardiopathies[tiab] or myocardiopathy[tiab] or cardiomyopathies, secondary[tiab] or cardiomyopathy, secondary[tiab] or secondary cardiomyopathies[tiab] or secondary cardiomyopathy[tiab] or secondary myocardial diseases[tiab] or disease, secondary myocardial[tiab] or diseases, secondary myocardial[tiab] or myocardial disease, secondary[tiab] or secondary myocardial disease[tiab] or myocardial diseases, secondary[tiab] or heart diseases[tiab] or heart disease[tiab] or cardiac diseases[tiab] or cardiac disease[tiab] or cardiac disorders[tiab] or cardiac disorder[tiab] or heart disorders[tiab] or heart disorder[tiab] or pericarditis[tiab] or pleuropericarditis[tiab] or endocarditis[tiab] or endocarditides[tiab] or infective endocarditis[tiab] or endocarditides, infective[tiab] or endocarditis, infective[tiab] or infective endocarditides[tiab] or heart damage[tiab] or cardiac injury[tiab] or acute cardiac injury[tiab] or cardiovascular abnormalities[tiab] or abnormalities, cardiovascular[tiab] or abnormality, cardiovascular[tiab] or cardiovascular abnormality[tiab] or cardiovascular infections[tiab] or cardiovascular infection[tiab] or infection, cardiovascular[tiab] or infections, cardiovascular[tiab] or cardiovascular diseases[tiab] or cardiovascular disease[tiab] or disease, cardiovascular[tiab] or diseases, cardiovascular[tiab] or heart arrest[tiab] or arrest, heart[tiab] or cardiac arrest[tiab] or arrest, cardiac[tiab] or asystole[tiab] or asystoles[tiab] or cardiopulmonary arrest[tiab] or arrest, cardiopulmonary[tiab] or ventricular dysfunction[tiab] or dysfunction, ventricular[tiab] or dysfunctions, ventricular[tiab] or ventricular dysfunctions[tiab] or heart failure[tiab] or diastolic heart failures[tiab] or heart failures, diastolic[tiab] or diastolic heart failure[tiab] or heart failure, diastolic[tiab] or cardiac failure[tiab] or heart decompensation[tiab] or decompensation, heart[tiab] or heart failure, right-sided[tiab] or heart failure, right sided[tiab] or right-sided heart failure[tiab] or right sided heart failure[tiab] or myocardial failure[tiab] or congestive heart failure[tiab] or heart failure, congestive[tiab] or heart failure, left-sided[tiab] or heart failure, left sided[tiab] or leftsided heart failure[tiab] or left sided heart failure[tiab] or heart failure, systolic[tiab] or heart failures, systolic[tiab] or systolic heart failures[tiab] or systolic heart failure[tiab] or troponin[tiab] or troponins[tiab] or troponin complex[tiab] 3. #1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e18 table 1: summary of the included studies author; year; country study design total study population mean age number of males diagnostic methods type of cardiac complication no. of patients tested for the complication no. of patients with the complication no. of deceased in patients with the complication no. of deceased in patients without the complication aggarwal s; 2020; usa retrospective 16 67 12 blood sample, echo acute cardiac injury 16 3 nr nr nr heart failure 16 2 nr nr blood sample abnormal troponin 16 10 nr nr arentz m; 2020; usa retrospective 21 70 11 blood sample, echo, clinical cardiomyopathy 21 7 nr nr blood sample abnormal troponin 21 3 nr nr baldi e; 2020; italy retrospective 9806 nr nr hospital report cardiac arrest 9806 362 nr nr barrasa h; 2020; spain prospective 48 63.2 27 nr myocarditis 48 1 nr nr chen c; 2020; china retrospective 150 59 84 blood sample abnormal troponin 150 22 nr nr chen t; 2020; china retrospective 274 62 171 nr acute cardiac injury 203 89 72 22 nr heart failure 176 43 41 42 blood sample abnormal troponin 203 83 68 26 deng q; 2020; china retrospective 112 65 57 blood sample abnormal troponin 112 42 nr nr deng y; 2020; china retrospective 225 54 124 blood sample acute cardiac injury 225 66 65 44 du ra; 2020; china prospective 179 57.6 97 blood sample abnormal troponin 179 31 13 8 du rb; 2020; china retrospective 109 70.7 75 blood sample abnormal troponin 109 52 nr nr du y; 2020; china retrospective 85 65.8 62 blood sample acute cardiac injury 85 38 nr nr clinical cardiac arrest 85 7 nr nr guo t; 2020; china retrospective 187 58.5 91 blood sample acute cardiac injury 187 52 31 12 han h; 2020; china retrospective 273 nr 97 blood sample abnormal troponin 273 27 13 8 he x; 2020; china retrospective 54 68 34 blood sample acute cardiac injury 54 24 18 8 hu l; 2020; china retrospective 323 61 166 blood sample acute cardiac injury 323 24 nr nr blood sample abnormal troponin 323 68 nr nr huang c; 2020; china prospective 41 49 30 blood sample abnormal troponin 41 5 nr nr acute cardiac injury 41 5 nr nr lei s; 2020; china retrospective 34 55 14 blood sample acute cardiac injury 34 5 4 3 li k; 2020; china retrospective 83 45.5 44 ct pericardial effusion 83 4 nr nr li x; 2020; china ambispective 548 60 279 blood sample acute cardiac injury 548 119 nr nr li y; 2020; china retrospective 54 61.8 34 blood sample acute cardiac injury 41 23 nr nr liu m; 2020; china retrospective 30 35 10 blood sample acute cardiac injury 30 5 nr nr ct: computed tomography scan; echo: echocardiography; ecg: electrocardiography; nr: not reported. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 10 table 1: summary of the included studies author; year; country study design total study population mean age number of males diagnostic methods type of cardiac complication no. of patients tested for the complication no. of patients with the complication no. of deceased in patients with the complication no. of deceased in patients without the complication liu y; 2020; china retrospective 76 45 49 blood sample abnormal troponin 76 14 nr nr ma k; 2020; china retrospective 84 48 48 blood sample abnormal troponin 84 36 0 0 blood sample, clinical symptom myocarditis 84 4 0 0 ruan q; 2020; china retrospective 150 nr nr nr acute cardiac injury 68 5 5 63 shi s; 2020; china retrospective 416 64 205 blood sample acute cardiac injury 416 82 42 15 wan s; 2020; china retrospective 135 47 72 blood sample acute cardiac injury 135 10 nr nr wang da; 2020; china retrospective 138 56 75 blood sample, ecg, echo acute cardiac injury 138 10 nr nr wang db; 2020; china retrospective 107 51 57 blood sample abnormal troponin 107 6 5 14 blood sample, ecg, echo acute cardiac injury 12 8 19 wang la; 2020; china retrospective 339 69 166 blood sample acute cardiac injury 339 70 39 26 blood sample, clinical symptom cardiac insufficiency 339 58 25 52 wang lb; 2020; china retrospective 202 63 88 blood sample acute cardiac injury 202 27 17 14 blood sample, ecg, echo cardiac insufficiency 202 24 14 19 blood sample abnormal troponin 202 27 nr nr wei j; 2020; china prospective 101 49 54 blood sample acute cardiac injury 101 16 3 0 xu x; 2020; china retrospective 90 50 39 ct pericardial effusion 90 1 nr nr yang f; 2020; china retrospective 92 69.8 49 blood sample acute cardiac injury 92 31 nr nr nr myocardial infarction 92 6 nr nr nr heart failure 92 2 nr nr blood sample abnormal troponin 92 31 nr nr yang x; 2020; china retrospective 52 59.7 35 blood sample acute cardiac injury 52 12 9 23 yao w; 2020; china retrospective 202 63.4 136 clinical cardiac arrest 202 4 0 21 zhang g; 2020; china retrospective 221 55 108 nr acute cardiac injury 221 17 nr nr zhao x; 2020; china retrospective 91 46 49 blood sample acute cardiac injury 91 14 nr nr blood sample abnormal troponin 88 3 nr nr zheng y; 2020; china retrospective 99 49.4 51 blood sample abnormal troponin 99 88 nr nr ct: computed tomography scan; echo: echocardiography; ecg: electrocardiography; nr: not reported. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e18 table 1: summary of the included studies author; year; country study design total study population mean age number of males diagnostic methods type of cardiac complication no. of patients tested for the complication no. of patients with the complication no. of deceased in patients with the complication no. of deceased in patients without the complication zhou f; 2020; china retrospective 191 56 119 blood sample abnormal troponin 145 24 23 31 heart failure 145 44 28 26 acute cardiac injury 145 33 32 22 zou x; 2020; china retrospective 178 60.68 67 blood sample, ecg, echo acute cardiac injury 154 45 34 18 blood sample abnormal troponin 154 33 28 24 ct: computed tomography scan; echo: echocardiography; ecg: electrocardiography; nr: not reported. figure 1: flow diagram of the present meta-analysis; cvd: cardiovascular disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 12 table 2: risk of bias assessment of included studies author; year item 1 item 2 item 3 item 4 item 5 item 6 item 7 item 8 item 9 item 10 item 11 item 12 item 13 item 14 aggarwal s; 2020 yes yes no yes no yes yes na yes na yes na yes no arentz m; 2020 yes yes yes yes no yes yes na yes na yes na yes no baldi e; 2020 yes yes yes no no yes yes na yes na yes na yes no barrasa h; 2020 yes yes yes yes no yes yes na yes na yes na yes no chen c; 2020 yes yes yes yes no yes yes na yes na yes na yes no chen t; 2020 yes yes no yes no yes yes na yes na yes na yes no deng q; 2020 yes yes yes yes no yes yes na yes na yes na yes no deng y; 2020 yes yes yes yes no yes yes na yes na yes na yes no du ra; 2020 yes yes yes yes no yes yes na yes na yes na yes no du rb; 2020 yes yes no yes no yes yes na yes na yes na yes no du y; 2020 yes yes yes yes no yes yes na yes na yes na yes no guo t; 2020 yes yes yes yes no yes yes na yes na yes na yes no han h; 2020 yes yes yes yes no yes yes na yes na yes na yes no he x; 2020 yes yes yes yes no yes yes na yes na yes na yes no huang c; 2020 yes yes yes yes no yes yes na yes na yes na yes no hu l; 2020 yes yes yes yes no yes yes na no na yes na yes no lei s; 2020 yes yes yes yes no yes yes na yes na yes na yes no li k; 2020 yes yes yes yes no yes yes na yes na yes na yes no liu m; 2020 yes yes yes yes no yes yes na yes na yes na yes no liu y; 2020 yes yes yes yes no yes yes na yes na yes na yes no li x; 2020 yes yes yes yes no yes yes na yes na yes na yes no li y; 2020 yes yes yes yes no yes yes na yes na yes na yes no ma k; 2020 yes yes yes no no yes yes na yes na yes na yes no ruan q; 2020 yes yes yes no no yes yes na yes na yes na yes no shi s; 2020 yes yes no yes no yes yes na yes na yes na yes no wang da; 2020 yes yes yes no no yes yes na yes na yes na yes no wang db; 2020 yes yes no no no yes yes na yes na yes na yes no wang la; 2020 yes yes yes yes no yes yes na yes na yes na yes no wang lb; 2020 yes yes yes yes no yes no na yes na yes na yes no wan s; 2020 yes yes yes yes no yes no na yes na yes na yes no wei j; 2020 yes yes yes yes no yes yes na yes na yes na yes no xu x; 2020 yes yes yes yes no yes yes na yes na yes na yes no yang f; 2020 yes yes yes no no yes yes na yes na yes na yes yes yang x; 2020 yes yes no yes no yes yes na yes na yes na yes no yao w; 2020 yes yes yes no no yes yes na yes na yes na yes no zhang g; 2020 yes yes yes no no yes yes na yes na yes na yes no zhao x; 2020 yes yes yes no no yes yes na yes na yes na yes no zheng y; 2020 yes yes yes no no yes yes na yes na yes na yes no zhou f; 2020 yes yes yes yes no yes yes na yes na yes na yes no zou x; 2020 yes yes yes yes no yes yes na yes na yes na yes no na: not applicable. items: 1. was the research question or objective in this paper clearly stated? 2. was the study population clearly specified and defined? 3. was the participation rate of eligible persons at least 50%? 4. were all the subjects selected or recruited from the same or similar populations (including the same time period)? were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? 5. was a sample size justification, power description, or variance and effect estimates provided? 6. for the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? 7. was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed? 8. for exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)? 9. were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? 10. was the exposure(s) assessed more than once over time? 11. were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? 12. were the outcome assessors blinded to the exposure status of participants? 13. was loss to follow-up after baseline 20% or less? 14. were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e18 table 3: summary of findings regarding cardiac complications in covid-19 complication number of studies prevalence 95% ci number of studies odds ratio 95% ci p acute cardiac injury 26 19.46 18.23, 20.72 14 14.24 8.67, 23.38 <0.001 abnormal troponin 19 22.86 21.19, 24.56 6 19.03 11.85, 30.56 <0.001 heart failure 4 19.07 15.38, 23.04 2 10.66 5.69, 19.97 <0.001 cardiac arrest 3 3.44 3.08, 3.82 1 0.04 0.00, >999.0 0.651 myocarditis 2 3.66 0.88, 7.82 1 1.00 0.00, >999.0 >0.99 pericardial effusion 2 2.62 0.58, 5.73 — — — — cardiac insufficiency 2 15.06 12.15, 18.22 2 4.65 2.82, 7.66 <0.001 cardiomyopathy 1 33.33 17.19, 54.63 — — — — myocardial infarction 1 6.52 3.02, 13.51 — — — — —: no data; ci: confidence interval this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 14 figure 2: funnel plot for publication bias in prevalence of cardiac complications in covid-19 patients and mortality rate after incidence of cardiac manifestation. there are evidences of publication bias among the studies, which reported prevalence of cardiac complications. while, no publication bias was observed regarding the relationship of cardiac complication and mortality in covid-19 patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2021; 9(1): e18 figure 3: forest plot for the assessment of the prevalence of acute cardiac injury in covid-19 patients; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 16 figure 4: forest plot for the assessment of the prevalence of abnormal troponin levels in covid-19 patients; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2021; 9(1): e18 figure 5: forrest plot for the assessment of risk of mortality in covid-19 patients with acute cardiac injury; or: odds ratio; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. toloui et al. 18 figure 6: forrest plot for the assessment of risk of mortality in covid-19 patients with abnormal troponin level; or: odds ratio; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion abbreviations declarations references archives of academic emergency medicine. 2022; 10(1): e4 ca s e re p o rt removal of coin cell lithium battery lodged in the pediatric pharyngoesophageal junction by rigid esophagoscopy; a case report hisataka ominato1, takumi kumai1,2∗, yasuaki harabuchi1 1. department of otolaryngology-head & neck surgery, asahikawa medical university, asahikawa, japan. 2. department of innovative head & neck cancer research and treatment (ihncrt), asahikawa medical university, asahikawa, japan. received: november 2021; accepted: november 2021; published online: 1 january 2022 abstract: a coin cell lithium battery is a common foreign body that can become lodged in the pediatric pharyngoesophageal junction. because the voltage of such batteries is relatively high, their rapid removal is necessary to avoid mucosal necrosis. despite being the initial choice for removal, flexible endoscopy cannot remove such foreign bodies from the esophagus. various removal methods, including rigid esophagoscopy, should be considered for removing lithium coin cell batteries. the transcervical approach is feasible for removing esophageal foreign bodies, but it carries the risk of complications such as esophageal stenosis. here we report a case of lithium coin battery ingestion that was successfully removed using a rigid esophagoscope. a 2-year-old girl was referred to a local doctor with cough and general fatigue. chest x-ray and flexible endoscopy revealed a coin cell lithium battery stuck in the pharyngoesophageal junction, but it could not be removed. the foreign body was removed using nishihata forceps through a rigid esophagoscope under general anesthesia. keywords: foreign bodies; esophagoscopes; pediatrics; surgical instruments cite this article as: ominato h, kumai t, harabuchi y. removal of coin cell lithium battery lodged in the pediatric pharyngoesophageal junction by rigid esophagoscopy; a case report. arch acad emerg med. 2022; 10(1): e4, doi: https://doi.org/10.22037/aaem.v10i1.1430. 1. introduction button batteries are widely used in a variety of household appliances. since the 1980s, button batteries have become common causes of pediatric foreign bodies in the esophagus (1). coin cell lithium batteries are 5–25 mm in diameter, making them susceptible to lodging in the pediatric pharyngoesophageal junction (2). since the voltage of the coin cell lithium battery is 3 v (versus 1.5 v in alkaline batteries) (3), severe tissue damage can be caused by the electric current of the coin cell lithium battery. as sodium hydroxide accumulates on the cathode interface of the coin cell lithium battery due to electrolysis (1, 4), histological changes and damage to the mucosa occur within 15 min and 2 hours of the battery contacting the mucosa, respectively (4). although flexible endoscopy is often the initial removal method (5), endo∗corresponding author: takumi kumai; department of otolaryngologyhead & neck surgery, asahikawa medical university, midorigaoka-higashi 21-1-1, asahikawa 078-8510, hokkaido, japan. email: t-kumai@asahikawamed.ac.jp, tel: +81-166-68-2554, orcid: https://orcid.org/0000-0002-3411671x. scopic forceps cannot effectively remove foreign bodies stuck in the pharyngoesophageal junction. here we report a case of a coin cell lithium battery foreign body that was difficult to remove using flexible endoscopy, but was successfully removed by rigid esophagoscopy. 2. case presentation a 2-year-old girl visited a local clinic with general fatigue and cough. the parents described that a coin cell lithium battery was missing at home. a chest x-ray showed a double contour, a typical finding of a coin cell lithium battery, in the upper esophagus (figure 1a), for which the patient was referred to a secondary referral hospital. although a coin cell lithium battery was detected in the esophagus using a flexible endoscope, the foreign body had adhered to the mucosa and was immobile, and it could not be removed using endoscopic forceps. four hours later, the intubated patient was referred to our hospital. a computed tomography scan showed a coin cell lithium battery with a 20 mm diameter in the upper esophagus (figure 1b). we first attempted to remove the battery using flexible endoscopy. the coin cell this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ominato et al. 2 figure 1: (a) a chest x-ray showing a coin cell lithium battery (double contour) lodged in the upper esophagus. (b) a computed tomography scan showed a coin cell lithium battery lodged in the upper esophagus. (c) endoscopic findings of the esophagus. the foreign body was stuck in the esophagus and resistant to endoscopic removal. (d) rigid esophagoscope. (e) nishihata forceps. lithium battery was tarnished black and had corroded the esophageal mucosa (figure 1c). due to adhesion, the foreign body could not be removed endoscopically. next, we performed rigid esophagoscopy to remove the battery. opening the pharyngoesophageal junction using a rigid esophagoscope revealed that part of the esophageal mucosa attached to the cathode interface of the coin cell lithium battery was ulcerated. although the foreign body was attached to the mucosa, it was successfully removed using nishihata forceps under rigid esophagoscopy (figures 1d, 1e). no mucosal perforation was evident. the cathode interface of the removed battery was corroded (figure 2a). the suspected duration of the battery–esophagus adhesion was at least 12 h. the patient was kept intubated for 10 days after removal of the battery, and treated with antibiotics (ampicillinsulbactam) to rest the esophageal mucosa. flexible endoscopy and esophagography showed esophageal ulceration without perforation, leakage, or stricture on postoperative day 10 (figures 2b, 2c). she was discharged on postoperative day 26 without any problems with oral intake. no evidence of esophageal stricture was detected during follow-up. 3. discussion a coin cell lithium battery is thin (1–6 mm thick) and has a diameter of approximately 20 mm. if accidentally swallowed, the battery is likely to stagnate at physiological constrictions of the esophagus including the pharyngoesophageal junction (2). the high voltage of the coin cell lithium battery induces more severe tissue damage compared to an alkaline battery (3). within 2 h, hydroxide ions generated on the cathode side of the battery through electrolysis damage the esophageal mucosa (4). recent epidemiological studies in the united states have reported that the number of accidents and serious complications involving the ingestion of batteries has been increasing, especially since the advent of lithium batteries (6). in detection of a coin cell lithium battery as a foreign body, the double contour sign is a characteristic finding on chest x-ray (7). complications associated with coin cell lithium battery ingestion include ulceration, esophageal stenosis, esophageal tracheal fistula, esophageal perforation, large vessel injury, mediastinitis, and recurrent nerve palsy (8). since corrosion is stronger on the cathode side of the battery, the anatomical region it contacts should be carefully examined to predict possible complications (9). immediate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e4 figure 2: (a) the cathode interface of the coin cell lithium battery was corroded. (b) flexible endoscopy showed esophageal ulceration without evident perforation. ulceration was localized to the mucosa where the cathode interface of the coin cell lithium battery was located. (c) esophagography showed no leakage or stricture. removal of the battery is required to avoid serious complications. flexible endoscopy, rigid esophagoscopy, and external cervical incisions are commonly used for esophageal foreign body removal (5). after removal, fasting and antibacterial drugs are prescribed to avoid infection and/or perforation through the mucosal ulcers. the use of steroids to prevent stricture after esophageal ulceration has been reported for alkaline burns; however, further investigations are required (10). flexible endoscopy is currently the minimally invasive approach of choice for removing foreign bodies in the upper digestive tract (5). however, the grasping power of tools applied in flexible endoscopy is weak, and endoscopic removal is not possible in cases of solid adhesions of the foreign body. in our case, flexible endoscopy, rigid esophagoscopy, and a transcervical incision kit were prepared, and the coin cell lithium battery was removed by rigid esophagoscopy within 1 h after the patient’s arrival. to avoid surgery-related complications, a transcervical incision should be considered the last option. the safety of rigid esophagoscopy is comparable to that of flexible endoscopy (5). the handling of a foreign body using forceps through rigid esophagoscopy is easier than when using endoscopic forceps, which has a weak grasping power. in this case, nishihata forceps, which are used in endoscopic sinus surgery, had suitable length and grasping power to remove the stuck battery from the pharyngoesophageal junction. the direct handling of foreign bodies by rigid esophagoscopy is a safe and effective approach for removing pediatric foreign bodies from the esophagus when flexible endoscopy is inapplicable. 4. conclusion although rigid esophagoscopy is a classic method, it is efficient for removing stuck foreign bodies from the pharyngoesophageal junction. various removal approaches should be considered to remove lithium coin cell batteries, which can induce severe mucosal damage. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ominato et al. 4 5. declarations 5.1. acknowledgments we would like to thank editage (www.editage.com) for english language editing. 5.2. authors’ contributions all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. ho and tk wrote the manuscript. yh helped shape the manuscript. 5.3. funding and support none. 5.4. conflicts of interest authors have no conflict of interest. references 1. jatana kr, chao s, jacobs in, litovitz t. button battery safety: industry and academic partnerships to drive change. otolaryngologic clinics of north america. 2019;52(1):149-61. 2. völker j, völker c, schendzielorz p, schraven sp, radeloff a, mlynski r, et al. pathophysiology of esophageal impairment due to button battery ingestion. international journal of pediatric otorhinolaryngology. 2017;100:77-85. 3. yamashlta m, saito s, koyama k, hattori h, ogata t. esophageal electrochemical burn by button-type alkaline batteries in dogs. veterinary and human toxicology. 1987;29(3):226-30. 4. jatana kr, rhoades k, milkovich s, jacobs in. basic mechanism of button battery ingestion injuries and novel mitigation strategies after diagnosis and removal. the laryngoscope. 2017;127(6):1276-82. 5. yang w, milad d, wolter ne, propst ej, chan y. systematic review of rigid and flexible esophagoscopy for pediatric esophageal foreign bodies. international journal of pediatric otorhinolaryngology. 2020;139:110397. 6. sharpe sj, rochette lm, smith ga. pediatric batteryrelated emergency department visits in the united states, 1990–2009. pediatrics. 2012;129(6):1111-7. 7. lin vy, daniel s, papsin b. button batteries in the ear, nose and upper aerodigestive tract. international journal of pediatric otorhinolaryngology. 2004;68(4):473-9. 8. litovitz t, whitaker n, clark l. preventing battery ingestions: an analysis of 8648 cases. pediatrics. 2010;125(6):1178-83. 9. litovitz t, whitaker n, clark l, white nc, marsolek m. emerging battery-ingestion hazard: clinical implications. pediatrics. 2010;125(6):1168-77. 10. bautista a, varela r, villanueva a, estevez e, tojo r, cadranel s. effects of prednisolone and dexamethasone in children with alkali burns of the oesophagus. european journal of pediatric surgery. 1996;6(4):198-203. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e17 ca s e re p o rt inferior hip dislocation in a 60-year-old man; a case report ali yeganeh1, nader tavakoli1, mohammad soleimani2, seyed nima taheri1, sahand cheraghiloohesara1∗ 1. trauma and injury research center, school of medicine, iran university of medical sciences, tehran, iran. 2. department of epidemiology, school of public health, iran university of medical sciences, tehran, iran. received: january 2022; accepted: january 2022; published online: 27 february 2022 abstract: inferior hip dislocation or luxatio erecta femoris is among the rarest hip dislocations, which has been described in limited studies. the patients usually present with their hip in flexion, abduction, and external rotation. hip dislocation is an orthopedic emergency, and a reduction needs to be performed promptly to avoid devastating complications such as avascular necrosis. here, we present a rare case of inferior hip dislocation in a 60-yearold man following a car-motorcycle collision. the patient presented to the emergency department with left hip flexion, abduction, external rotation, and inability to move his leg due to pain. closed reduction under procedural sedation was attempted in the emergency department once, which was unsuccessful. the patient was then taken to the operating room for another attempt of closed reduction under general anesthesia. the patient was discharged after two days with pin traction and double crutches. after two weeks, the pin was removed, and full weight-bearing was permitted. after 12 weeks, the patient had mild pain with unusual activity and slight limping; however, imaging revealed no signs of any complications. keywords: hip dislocation; joint dislocations; case reports; wounds and injuries cite this article as: yeganeh a, tavakoli n, soleimani m, taheri sn, cheraghiloohesara s. inferior hip dislocation in a 60-year-old man; a case report. arch acad emerg med. 2022; 10(1): e17. https://doi.org/10.22037/aaem.v10i1.1498. 1. introduction as the most stable joint, the hip requires much energy to be dislocated; so, hip dislocations comprise 5% of all joint dislocations (1). not surprisingly, most hip dislocations are due to high-energy trauma. hip dislocations are categorized into three main groups: posterior, central, and anterior (2). the most frequently observed subtype of hip dislocations is posterior dislocation, whereas anterior dislocation is the rarest, comprising less than 10% of all hip dislocations (1). anterior dislocations are further categorized into superior and inferior dislocation or luxatio erecta femoris (3, 4). inferior hip dislocation comprises 5% of all traumatic hip dislocations. (1, 5, 6). here, we present a rare case of inferior hip dislocation with no concomitant injury or fracture, managed through closed reduction. ∗corresponding author: sahand cheraghiloohesara; hazrate rasool akram hospital, niayesh st, satarkhan av, tehran, iran; postal code: 1449614535; telephone number: 00982164352264, fax number: 00982166502248, email: sahand.cheraghi@gmail.com, orcid: https://orcid.org/0000-00017702-7656. 2. case presentation a 60-year-old man presented to our emergency department following a car vs. motorcycle collision, in which the patient was the biker. he was brought to our hospital by the emergency medical service. upon arrival, the patient was complaining of pain, his left hip was in flexion, abduction, and external rotation, and he was unable to move the leg. apart from skin abrasions and deformity in the left hip, the primary survey was unremarkable. in the secondary survey, there was tenderness in the left hip, limited range of motion, no neurologic deficits, and normal distal pulses of the limb. the patient recalled the incident and complained of constant severe pain in the left groin after the incident, which worsened by limb movement. a radiograph showed inferior hip dislocation (figure 1a). a computed tomography (ct) scan confirmed the diagnosis and showed no sign of fracture (figure 1b). physical examination and imaging revealed no other injuries than hip dislocation. closed reduction under sedation with propofol and midazolam was tried in the emergency department, which was unsuccessful. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. yeganeh and et al. 2 figure 1: (a) primary pelvic x-ray radiograph, (b) pre-reduction computed tomography (ct) scan. next, the patient was taken to the operating room for another attempt at closed reduction under general anesthesia. the patient lied in the supine position on the operating table, and the hip was reduced in the first attempt using the allis maneuver. then, the range of motion was evaluated, which was normal, and the hip was stable. the concentric reduction was confirmed via fluoroscopy in the operating room, and post-operative pelvic radiograph and computed tomography (ct) scan (figure 2). after the reduction, pin traction and a knee immobilizer were used for the patient. then he was admitted to the orthopedic surgery ward and was on complete bed rest for the next two days until discharge. upon discharge, he was instructed on partial weight-bearing on the injured limb and using double crutches for the next two weeks. figure 3 shows the results of the patient’s pelvic imaging during the 12-week follow-up. two weeks later, the patient presented to the hip clinic for his first follow-up. he had no complaint of pain. in physical examination, the range of motion was normal, and the hip was stable. also, there was no tenderness in the left hip. the pin traction was removed, and full-weight bearing was permitted. for his subsequent follow-up, the patient presented to the clinic after another two weeks and reported mild pain and returning to normal daily activity without any difficulty. in the physical examination, he had slight limping in gait, a normal range of motion of the hip, and no tenderness. also, the imaging showed no sign of any complications. two months later, 12 weeks after the reduction, the patient returned for his next appointment. he reported mild pain with unusual activities, and the physical examination indicated slight limping in the gait, while palpitation, range of motion, and stability of the joint were normal. a harris hip score of 73 was calculated for the patient. pelvic radiograph and ct scan were obtained, which showed no signs of any complications. figure 2: reduction confirmed by fluoroscopy in the operation room, pelvic x-ray radiograph (a), and coronal (b) and axial (c) views of pelvic computed tomography scan. 3. discussion bigelow first described traumatic hip dislocation in 1869, since then, hip dislocation’s main injury pattern has changed from horseback riding to motor vehicle accidents (7). these injuries mostly affect young men and result from a motor vehicle accident in up to 93% of cases. other causes include pedestrian accidents, falls, and sports (1, 3, 7). since the hip is a very stable joint due to the surrounding muscle and ligament structures that provide protection, hip dislocations mainly occur following high-energy trauma (1, 7, 8). however, in children, these injuries generally occur after low-energy trauma due to the acetabulum structure and laxity of joints (9). hip dislocation comprises 5% of all joint dislocations and is categorized into the anterior, central, and posterior main groups (2). posterior dislocation is the most common subtype, and anterior dislocation is the rarest, and the ratio of posterior to anterior dislocations is reported to be between 10:1 to 19:1 (7). anterior dislocation is itself divided into superior and inferior dislocations (2-4, 10). inferior hip dislocations are responsible for almost 5% of all traumatic hip dislocations (1, 5, 6). ocurrence of a superior or inferior dislocation depends on the position of the hip at the time of trauma. trauma to a hip in extension, abduction, and external rotation results in superior dislocation, while trauma to a flexed, abducted, and externally rotated hip results in inferior hip dislocation (7). hip dislocation is an orthopedic emergency, and the cornerthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e17 figure 3: follow-up imaging of patient at various times after reduction. stone of treatment is timely diagnosis and reduction (7). also, traumatic hip dislocation is usually associated with several other traumas, including head, neck, chest, and abdomen, and femoral head or neck fractures (2, 9). thus, obtaining pelvic radiographs is required to prevent the overlooking of possible hip dislocations (7). several studies indicate that the treatment of choice is closed reduction if there is no sign of fracture or loose fragments (5, 9-12). however, several attempts on the closed reduction may itself lead to complications and is contraindicated, as the success rates of open and closed reduction are reported to be the same (1, 7). there is no consensus over the post-reduction management (7). older studies prefer prolonged immobilization, prevention of weight-bearing, and traction. however, no studies support these methods, and a shorter period of immobilization and non-weight-bearing may result in the same outcomes (3, 7). hip dislocation is an orthopedic emergency and can lead to several complications (5). a terrifying complication of hip dislocation is avascular necrosis (avn) of the femoral head (5, 13). jacob et al. indicate a significant reduction in avn with prompt diagnosis and management, i.e., within the first six hours; thus, promptly reducing the dislocated hip is crucial (7, 10, 14). other significant complications of hip dislocation include arthritis, nerve injury, and myositis ossificans, and the patient should be followed to promptly diagnose and manage these complications (11). 4. conclusion hip dislocation is rare and usually occurs following highenergy traumas, and inferior dislocation is among the rarest. these injuries may result in avn and arthritis, and it is crucial to promptly diagnose and manage them within the first six hours to avoid complications. 5. declarations 5.1. acknowledgments we would like to thank the patient for granting us permission to use his data. also, we would like to thank dr. amir sobhani eraghi and dr. masoud aslani for their contributions to this study. 5.2. author contribution nt met the patient in the emergency department. ay, nt, and sc reduced the hip in the operating room. nt and ay suggested the concept of work. ms, nt, and sc made data acquisition. ms wrote the first draft, which was read and revised by all others. all authors approved the final version for submission and agreed to be accountable for all aspects of the work. 5.3. funding and support the authors did not receive support from any organization for the submitted work. 5.4. conflict of interest none. 5.5. data availability authors guarantee that data of the study is available and will be provided to anyone needing it. 5.6. ethical issues written informed consent was obtained from the patient, and the study was approved by the ethics committee of the iran university of medical sciences under the code ir.iums.rec.1400.765. references 1. de oliveira al, machado eg. open anterior dislocation of the hip in an adult: a case report and review of literature. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. yeganeh and et al. 4 revista brasileira de ortopedia. 2014;49(1):94-7. 2. kiel j, genova r. inferior hip dislocation in a 16 year old. the american journal of emergency medicine. 2021;46:798.e1-798.e3. 3. day ma, duchman kr, noiseux no. traumatic obturator dislocation following total hip arthroplasty managed with closed reduction: a case report and review of the literature. jbjs case connector. 2017;7(3):e66. 4. syam k, saibaba b, aggarwal s, santhanam s, palanisamy g. update review and clinical presentation in adult inferior dislocation of hip. european journal of orthopaedic surgery & traumatology. 2017;27(8):1039-1044. 5. hani r, kharmaz m, berrada ms. traumatic obturator dislocation of the hip joint: a case report and review of the literature. pan african medical journal. 2015;21(1):55. 6. epstein h. traumatic anterior dislocation of the hip; management and results: an analysis of fifty-five cases. journal of bone and joint surgery american. 1972;54:1561-1562. 7. sahin v, karakas es, aksu s, atlihan d, turk cy, halici m. traumatic dislocation and fracture-dislocation of the hip: a long-term follow-up study. journal of trauma and acute care surgery. 2003;54(3):520-529. 8. tao q, zhong f, wang c, wang h, chen c, wu f, et al. traumatic obturator dislocation of the hip joint associated with greater trochanter fracture: a case report. orthopaedic surgery. 2021;13(2):673-677. 9. jain s, haughton ba, grogan rj. inferior dislocation of the hip: a case report and literature review. journal of orthopaedic surgery. 2015;23(1):123-6. 10. ismael s, vora j, thomas p. adult traumatic inferior hip dislocation: rare case ended with open reduction. journal of orthopaedic case reports. 2017;7(1):101-104. 11. duygulu f, karaoglu s, kabak s, karahan oi. bilateral obturator dislocation of the hip. archives of orthopaedic and trauma surgery. 2003;123(1):36-8. 12. cao z, zhu d, li c, li yh, tan l. traumatic anterior hip dislocation with associated bilateral femoral fractures in a child: a case report and review of the literature. pan african medical journal. 2019;32:88. 13. ceri l, zanna l, buzzi r, de biase p. obturator dislocation of the hip associated with ipsilateral quadrilateral plate fracture: a rare case report. trauma case reports. 2021;32:100451. 14. jacob jr, rao jp, ciccarelli c. traumatic dislocation and fracture dislocation of the hip. a long-term followup study. clinical orthopaedics and related research. 1987(214):249-263. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2017; 5 (1): e43 ca s e re p o rt head trauma as a precipitating factor for late-onset leigh syndrome: a case report farzad ashrafi1∗, hossein pakdaman1, mehran arabahmadi1, behdad behnam1 1. brain mapping research center, shahid beheshti university of medical sciences, tehran, iran. received: october 2016; accepted: october 2016; published online: 14 january 2017 abstract: leigh syndrome is a severe progressive neurodegenerative disorder with different clinical presentationsthat usually becomes apparent in the first year of life and rarely in late childhood and elderly years. it is causedby failure of mitochondrial respiratory chain and often results in regression of both mental and motor skills and might even lead to death. in some of the inherited neurodegenerative diseases like alexander disease, head trauma is reported as a trigger for onset of the disease. we present a late onset leigh syndrome in a 14-year-old girl whose symptoms were initiating following head trauma. keywords: leigh disease; craniocerebral trauma; precipitating factors © copyright (2017) shahid beheshti university of medical sciences cite this article as: ashrafi f, pakdaman h, arabahmadi m, behnam b. head trauma as a precipitating factor for late-onset leigh syndrome: a case report. emergency. 2017; 5 (1): e43. 1. introduction leigh syndrome (ls) is a rare progressive neurodegenerative disorder, whichusuallymanifests in early childhood. more than 75 gene mutations, related to pyruvate metabolism and mitochondrial respiration, have been found responsible for ls (1). although ls often occurs in early childhood, there are few reports of late-onset presentation (2). basal ganglia, cerebellum and brain stem are typically involved by necrotizing changes. the most common manifestations include psychomotor involvement, ataxia, dystonia, seizures, nystagmus, ophthalmoplegia, and respiratory distress (3, 4). this syndrome can present with a variety of clinical presentations, progression and prognosis (5). however, all previous cases have been reported without any trigger before the onset of symptoms. in this report, we present a 14-year-old girl who initially developed seizure and ataxia following head trauma, and finally the diagnosis was proved based on manifestations, characteristic imaging findings and dramatic response to mitochondrial cocktail. ∗corresponding author: farzad ashrafi; department of neurology, shohadaye tajrish hospital, vali-asr street, tajrish square, tehran, iran. tel:+982122718003; mobile:+989121937930; email: farzad.ashrafi@gmail.com 2. case presentation: the patient was a 14-year-old girl of consanguineous parents admitted to our emergency department with complaint of respiratory distress. she had no family history of neurological disorders and had just one 18-year-old sister who was in excellent health. she had no significant past medical history except mild bilateral hearing loss. her problem first started with a generalized tonic clonic seizure following head trauma during sportsclassin school 9 months ago. according to her parents’ report, she had about one minute postictal phase after her first episode of seizure. she was admitted to hospital and tooklamotrigin and phenytoin that were discontinued gradually by improvements of her symptoms. two month later, she developed ataxia, difficulties with walking and generalized weakness. at that time, her neurological examinations revealed no abnormalities except spastic tone of muscles and upward plantar reflex. her blood biochemistry, urine analysis, and cerebrospinal fluid (csf) study were all within normal limits except for increased serum pyruvate level (2 mg/dl, normal: 0.3 0.7) and elevated csf lactate (3.2 mmol/l; normal: 1.12.3). in addition, urine copper, serum copper and ceruloplasminlevels were in normal range. brain magnetic resonance imaging (mri) showed symmetric bilateral hypersignal lesions in basal ganglia accompanied by isosignal lesions in splenium and corpus callossum (figure1). basal ganglia lesions were negative on diffusion weighted (dw ) while this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. ashrafi et al. 2 figure 1: bilateral basal ganglia hyper-intensities on brain magnetic resonance imaging (mri). splenium and corpus callossum were positive, restricted with low apparent diffusion coefficient (figure 2). magnetic resonance spectroscopy also reported an abnormal hyper intensity with near symmetrical configuration in periventricular region, brain stem and medulla with lactate rise and diffusion restriction compatible with mitochondrial disorders or glutaricaciduria.electromyography/nerve conduction velocity (emg/ncv ) revealed axonal polyneuropathy with neurogenic changes without active denervation (figure 3). ophthalmology consultation was negative for retinitis pigmentosaand kayser–fleischer ring. with the impression of metabolic disease, she was treated with co q10, vitamin b1, l-carnitine and b-complex (mitochondrial cocktail) and dramatically responded to treatment and her neurological conditions improved. she was discharged without any complaint and suggested to come back to clinic with genetic study report, complete treatment and follow up. two weeks later she presented to emergency room with respiratory distress. on admission, she was ill and not oriented. her blood pressure was 140/70 mmhg, pulse rate of 141/minute, respiratory rate of 45/minute, temperature 37.3◦cand o2 saturation 89%. her arterial blood gas analysis revealed ph of 7.40, pao2 of 60.2, paco2 of 27 and hco3 of 16. general examinations were normal except tachypneic breathing with subcostal retraction. her neurological examination was remarkable for left eye deviation (abducent nerve paresia) and generalized weakness. her lower limb muscular force was 3/5. she was intubated and supportive therapy was begun for her.she had cardiac arrest and died despite cardiopulmonary resuscitation. three days later, her genetic study revealed homozygote mutation (35 del g) in evaluation of entire coding regions of gjb2 and confirmed the diagnosis of ls. a diagnosis of late-onset ls was made based on radiological and response to mitochondrial cocktail. figure 2: restriction of the lesions on diffusion weighted (dw ) brain magnetic resonance imaging(mri). figure 3: reduced amplitude of the right and left median motor nerves on nerve conduction velocity (ncv ). 3. discussion: ls is categorized as a mitochondrial encephalomyelopathies. defect in enzyme pathway for respiratory metabolism has been known as an underlying factor (6). in this case, the most interesting aspect was the head trauma as a possible precipitating factor in developing seizure and other symptoms in a previously normal child that finally led to diagnosis of ls. up to now, few cases have been reported who developed neurological disorders with underlying gene mutation following head trauma. in 2010, namekawa et al, reported an adult onset of alexander disease in a 60 year old man whose symptoms initiated after head trauma (7). furthermore, hayashi et al.presented a 34-year-old man who developed a gradual visual problem about 6 months after an accident and was finally diagnosed with leber’s hereditary optic neuropathy (8). moreover, association between traumatic brain injury and mitochondrial pathway defect has been shown previously (9). our case, together with previous case reports raised the possibility of trauma being a precipitating factor in developing or progression of mitochondrial disorders. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e43 4. conclusion this case showed the possible role of triggers such as head trauma in developing ls in patients with underlying genetic defect. 5. appendix 5.1. acknowledgements the authors wish to thank all the staff of emergency and neurology departments of shohadayetajrish hospital, tehran, iran. 5.2. author’s contribution the authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest none. 5.4. funding none. references 1. lake nj, compton ag, rahman s, thorburn dr. leigh syndrome: one disorder, more than 75 monogenic causes. annals of neurology. 2016;79(2):190-203. 2. sakushima k, tsuji-akimoto s, niino m, saitoh s, yabe i, sasaki h. adult leigh disease without failure to thrive. the neurologist. 2011;17(4):222-7. 3. finsterer j. leigh and leigh-like syndrome in children and adults. pediatric neurology. 2008;39(4):223-35. 4. baertling f, rodenburg rj, schaper j, smeitink ja, koopman wj, mayatepek e, et al. a guide to diagnosis and treatment of leigh syndrome. journal of neurology, neurosurgery & psychiatry. 2014;85(3):257-65. 5. lee js, kim h, lim bc, hwang h, choi j, kim kj, et al. leigh syndrome in childhood: neurologic progression and functional outcome. journal of clinical neurology. 2016;12(2):181-7. 6. rahman s, blok r, dahl hh, danks d, kirby d, chow c, et al. leigh syndrome: clinical features and biochemical and dna abnormalities. annals of neurology. 1996;39(3):34351. 7. namekawa m, takiyama y, honda j, shimazaki h, sakoe k, nakano i. adult-onset alexander disease with typical" tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature. bmc neurology. 2010;10(1):1. 8. hayashi s, okamoto k. [leber’s hereditary optic neuropathy after head trauma: a case report]. rinsho shinkeigaku= clinical neurology. 2011;51(10):781-3. 9. wong vs, langley b. epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy. neuroscience letters. 2016;625:26-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion: conclusion appendix references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 27 emergency (2013); 1 (1): 27-29 photo quiz a 33-year-old woman with severe postpartum headache hosein delavar kasmaei1, alireza baratloo2, maryam soleymani1* 1. department of neurology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran brain imagines figure1: axial ct1scan. figure2: t2-weighted sequence in mri2. figure3: coronal view of mrv3. figure 4: t2-weighted sequence of mri with gadolinium. figure 5: flair sequence of mri with gadolinium. 1: computed tomography, 2: magnetic resonance imaging, 3: magnetic resonance venography cite this article as: delavar kasmaei h, baratloo a, soleymani m. photo quiz: a 33-year-old woman with severe postpartum headache. emergency. 2013; 1(1): 27-9. case presentation:1 atient was a 33-year-old woman underwent her first time cesarean section combined with spinal epidural anesthesia 5 days before and discharged the day after with good condition. she got severe headache with pain score about 8-9, 2 days after discharge from hospital. her headache was severe, bilateral, pulsatile and almost likely sudden onset accompanied with nausea that mildly progressed after starting. she went to the hospital, which her delivery was taken; with impression of post dural puncture headache (pdph) 10mg iv morphine sulfate was administered totally and sub *corresponding author: maryam soleymani; department of neurology, shohadaye tajrish hospital, tajrish square, tehran, iran. 1617763141; mobile phone: +989117042319; phone/fax: +982122721155. email: dr_maya_s@yahoo.com received: 10 october 2013; accepted: 14 october 2013 sequently discharged home with relative decreased headache. the day after first headache attack, when she admitted in our hospital, claimed that could not hold her baby for breast-feeding. in minimental status examination, time disorientation was obvious but orientation to place and person was intact. in motor examination, we found right side hemiparesis and decreased right upper and lower limbs tone. brain computed tomography (ct) scan and magnetic resonance imaging (mri) revealed a massive cortico-subcortical hemorrhagic infarction on left parieto-occipital lobes (figure 1, 2). with attention to significant nonhomogeneous occupying lesion, brain mri with gadolinium and magnetic resonance venography (mrv) were performed (figures 3-5). what is your diagnosis? p mailto:dr_maya_s@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 28 delavar kasmaei et al diagnosis: cortical cerebral vein thrombosis discussion: cortical cerebral vein thrombosis is a rare but serious emergency manifestation during pregnancy and postpartum that can present by a wide variety of nonspecific symptoms which headache is the most frequent and often the earliest one (1). headache in the postpartum period can be a manifestation of different diseases including eclampsia, post dural puncture headache (pdph) and cerebral venous thrombosis (2). the evaluation of postpartum headache should be performed with appropriate method and multidisciplinary approach. patients without focal neurologic deficit and without findings that are consistent with preeclampsia should be considered initially to have tension-type or migraine headache. severe headaches resistance to common pain management particularly when accompanied with focal neurologic deficit always require brain imaging (3). during pregnancy, fibrinolytic activity is reduced and on the other hand more coagulation factors are produced, resulting in a physiological hypercoagulatory status in the last trimester of pregnancy and especially the puerperium (4). furthermore, acute blood loss during delivery, prolonged lying in bed, and postpartum infection sweating, and hyperlipidemia dramatically increase the chance of venous thromboembolism (5). in some studies cesarean section (cs) were mentioned as important risk factor for both stroke and intracranial venous thrombosis. however, it is likely that the dramatic changes occurring after delivery are the most significant factors, intensified by the relatively long time spent in bed after cs and cs itself seems to contribute little to cerebral vein thrombosis (5, 6). cerebral vein thrombosis induced headache can be of any grade of severity; usually is global, persistent, and has an acute onset. making correct diagnosis may be so difficult when headache occurs in the absence of any other neurologic sign. focal or generalized seizures occur in about 40% of the cvt cases. papilledema, cranial nerve palsies, incomplete hemianopia, hemiparesis, aphasia, various cognitive or psychiatric disturbances and impaired mental status which may fluctuate over days are all count as other clinical manifestations that can be find depend on the location of cerebral lesions and/or the development of raised intracranial pressure. in cases of cortical vein thrombosis, intracranial pressure is not elevated, as it is when the dural venous sinuses are occluded (7). the headache can often be difficult to distinguish from pdph as it may have a postural component. indeed, several cases of cerebral or cortical vein thrombosis have been associated with pdph, possibly secondary to cerebral vasodilatation after cerebrospinal fluid (csf) leak and prolonged dehydration (2). definite diagnosis is based on both clinical manifestations and imaging findings. the diagnosis can be suspected from brain computed tomography (ct) scan, although sometimes it is normal, and be confirmed with conventional angiography or ct angiography or mri combined with mr angiography of the brain, the latter thought to be the diagnostic procedure of choice. the diagnosis of cortical vein thrombosis is now made by careful examination of the mrv or by the venous phase of the conventional angiogram. cortical vein thrombosis should be suspected in the situation of multiple hemorrhagic infarctions in one hemisphere without a source of embolism or atherothrombosis (8). anticoagulation can be effective for the prevention and treatment of extensive cortical vein thrombosis, and should be administered even when thrombosis is complicated by cerebral bleeding. appropriate anticoagulation is generally not associated with any additional risk of intracranial bleeding (5). in patients with severe involvement of multiple sinuses and veins, anticoagulation alone has limited effects on the lysis of deep cerebral venous thromboses and thrombolytic combined with anticoagulation may be more effective (9). although early diagnosis and prompt appropriate treatment are strongly associated with a good prognosis, the scarcity and various manifestations of pregnancyassociated cortical vein thrombosis cause that physicians have little understanding of its progression and diagnoses may often be wrong or delayed (5). however, cerebral vein thrombosis remains a potentially life-threatening complication. markedly impaired consciousness upon presentation, hemorrhage found at the brain ct scan on admission, delay in diagnosis and therefore in the treatment, are poor prognostic factors (7). the lack of required high index of suspicion probably due to the rare incidence of hemorrhagic cortical vein thrombosis, contribute to initial misdiagnosis as a case of intracranial hemorrhage and a delay in the starting the treatment with anticoagulation present in several of the reported cases in the literature, indicating the need for a reminder (10). case fate: mrv (figure 3) showed decreased signal in left trolard or superior anastomotic vein. diagnosis of cortical cerebral vein thrombosis confirmed based on history, mri and mrv findings. the patient underwent anticoagulant therapy and discharged 10 days after with warfarin tablet with good condition. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 29 emergency (2013); 1 (1): 27-29 the patient visited after 2 months, had no headache or any neurologic deficit. acknowledgment: we would like to express our special thanks from emergency neurology department staffs of shohadaye tajrish hospital. conflict of interest: there was no conflict of interest. authors’ contribution: all authors contribute in drafting/revising the manuscript, study concept or design, and interpretation of data. references 1. macarthur a. postpartum headache. in: chestnut dh pl, tsen lc, wong ca, editor. chestnut’s obstetric anesthesia principles and practice. 4th ed. philadelphia: mosby elsevier; 2009. p. 677–700. 2. sabharwal a, stocks g. postpartum headache: diagnosis and management; continuing education in anaesthesia. crit care pain. 2011;11(5):181-5. 3. stella cl, jodicke cd, how hy, harkness uf, sibai bm. postpartum headache: is your work-up complete? am j obstet gynecol. 2007;196(4):1-7. 4. vodnik t, ignjatovic s, majkic-singh n. changes in the plasma levels of protein c system parameters in pregnancy. scand j clin lab invest. 2003;63(7-8):481-8. 5. gao h, yang b-j, jin l-p, jia x-f. predisposing factors, diagnosis, treatment and prognosis of cerebral venous thrombosis during pregnancy and postpartum: a casecontrol study. chin med j. 2011;124(24):4198. 6. lanska dj, kryscio rj. risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. stroke. 2000;31(6):1274-82. 7. stam j. thrombosis of the cerebral veins and sinuses. n engl j med. 2005;352(17):1791-8. 8. rizzo l, crasto sg, rudà r, et al. cerebral venous thrombosis: role of ct, mri and mra in the emergency setting. radiol med. 2010;115(2):313-25. 9. murugappan a, coplin w, al-sadat a, et al. thrombolytic therapy of acute ischemic stroke during pregnancy. neurology. 2006;66(5):768-70. 10. chan k, cheung r, liu w, mak w, ho s. cerebral venous thrombosis in a gentleman presenting with fever, convulsion and frontotemporal haemorrhages. j clin neurosci. 2005;12(2):186-8. archives of academic emergency medicine. 2021; 9(1): e29 https://doi.org/10.22037/aaem.v9i1.1059 or i g i n a l re s e a rc h early detection of rhabdomyolysis-induced acute kidney injury through machine learning approaches pooria poorsarvi tehrani1, hamed malek1∗ 1. faculty of computer science and engineering, shahid beheshti university, tehran, iran. received: january 2021; accepted: february 2021; published online: 25 march 2021 abstract: introduction: rhabdomyolysis-induced acute kidney injury (aki) is one of the most common complications of catastrophic incidents, especially earthquakes. early detection of aki can reduce the burden of the disease. in this paper, data collected from the bam earthquake was used to find a suitable model that can be used in prediction of aki in the early stages of the disaster. methods: models used in this paper utilized many inputs, which were extracted from the previously published dataset, but depending on the employed method, other inputs have also been considered. this work has been done in two parts. in the first part, the models were constructed from a smaller set of records, which included all of the required fields and in the second part; the main purpose was to find a way to replace the missing data, as data are mostly incomplete in catastrophic events. the data used belonged to the victims of the bam earthquake, who were admitted to different hospitals. these data were collected on the first day of the incident via questionnaires that were provided by the iranian society of nephrology, in collaboration with the international society of nephrology (isn). results: overall, neural networks have more robust results and given that they can be trained on more data to gain better accuracy, and gain more generalization, they show promising results. overall, the best specificity that was achieved on testing almost all of the records was 99.24% and the best sensitivity that was achieved in testing almost all of the records was 94.44%. conclusion: we introduced several machine learning-based methods for predicting rhabdomyolysis-induced aki on the third day after a catastrophic incident. the introduced models show higher accuracy compared to previous works performed on the bam earthquake dataset. keywords: acute kidney injury; clinical decision rules; machine learning; neural networks, computer; decision making cite this article as: poorsarvi tehrani p, malek h. early detection of rhabdomyolysis-induced acute kidney injury through machine learning approaches. arch acad emerg med. 2021; 9(1): e29. 1. introduction rhabdomyolysis-induced acute kidney injury (aki) is one of the main medical complications of catastrophes, and is the second leading cause of death in traumatic injuries. after being pulled out from the rubble, dehydration and circulatory defects may occur, which can eventually lead to aki (1). a lot of work has been done for predicting aki, in most of which electronic health records (ehr) and a logistic regression to predict the state of a patient (2-5) or a linear regression to predict another value are used, so that they can predict the state of the patient using an estimated value (6). even though a great amount of research has been done in this field, most of the models proposed in the past have a trade∗corresponding author: hamed malek; shahid beheshti university, shahid shahriari square, daneshjou boulevard, shahid chamran highway, tehran, iran. email: h_malek@sbu.ac.ir, phone/fax: +98 (21) 29904106. off on sensitivity and specificity. after training these models for some time they either gain a relatively very high sensitivity or very high specificity. most of the models are also trained on ehrs with lots of columns and very little missing data, and although they are useful in training a machine learning model that is not the case in catastrophic events, in which most of the time the information is only partially available. most of these models use linear or logistic regression and even though these models are easier to implement in a decision support system (dss), they might fail to capture some of the non-linearities in the data. the proposed models in this paper will try to use non-linear models to reach a better accuracy and also to reach a sensible level of invariance to the loss of information. 2. methods the dataset used in this study is from najafi et al. (6), which was collected by the iranian society of nephrology, in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. poorsarvi tehrani and h. malek 2 collaboration with the international society of nephrology (isn) on the first day of the bam earthquake. in that work, a questionnaire was developed and sent to all hospitals that were involved in the treatment of patients. in addition to basic demographic data, some biochemical factors were collected, which include serum creatinine, creatine phosphokinase (cpk), lactate dehydrogenase (ldh), serum glutamic-oxaloacetic transaminase (sgot), uric acid, calcium (ca), phosphorus (p), sodium (na), potassium (k), white blood cell count (wbc) and platelet count (plt). the details of the protocol including the eligibility criteria have been presented in their article (6). due to sparsity of data, the procedure of building the final models was performed in two parts. in the first part, we tried to construct the models only based on the parts of the bam dataset that were employed in the work of najafi et al. (6) and in the second part of the paper, a method that can be used in order to use all of the bam dataset is proposed. so, the models were built in the following order: models built from records with available fields regression plus classification neural networks (rc_nn). in the first stage, records that have all of the desired fields (cpk, ldh, potassium, uric acid, and creatinine on the 3r d day) are employed to build a prediction model for creatinine on the 3r d day, and in the second stage, a classification neural network is used to predict aki occurrence. full neural network model (fnnm). using a neural network instead of a threshold to predict whether or not someone is diagnosed with aki. this is the second part of our rc_nn. using genetic programming to predict whether or not someone is diagnosed with aki. models built from all records using two neural networks with different neural network architectures. using a support vector machine (svm) to predict whether or not someone is diagnosed with aki. using a random forest, to predict whether or not someone is diagnosed with aki. using the last four models to make an ensemble model, to predict whether or not someone is diagnosed with aki. for the implementation of the algorithms, all of the neural network models were made using keras (7) with the back end of tensorflow (8) and the random forest and the support vector machine models were made using scikit-learn. the model that uses genetic programming was made using gp learn, a python library. 2.1. models on partial data from the bam earthquake in this section, in order to build a model, biochemical factors used in the work of najafi et al. (6) were employed and any record that had missing information was removed. the biochemical factors used in this part are: cpk, ldh, potassium, and uric acid. the aforementioned factors are used either to predict the state of a patient directly or to predict the value of creatinine on the third day, so that it can later be used in order to predict the state of a patient. 2.1.1 predicting using neural networks in the first model, two different parts, both of which are neural networks, were employed. the first one is used to predict the normalized value of creatinine on the third day; the second neural network is used to predict whether or not someone should be diagnosed with aki considering the predicted value of creatinine on the third day. the architecture of the models is presented in figure 1. 2.1.2 using a neural network instead of a threshold in the second model, a neural network was used instead of using a threshold on the predicted value of creatinine on the third day. this model had more accuracy on the 553 rows that had the value of creatinine on the third day than the single threshold that was introduced in the work of najafi et al. (6). 2.1.3 using genetic programming to predict the state of patients genetic programming is a method that is inspired by biological evolution. first, different individuals or candidates are created. then, these individuals are combined and at times mutated so that they can change over time. these individuals are also evaluated at each step so that the ones that have better performance (fitness), which is their accuracy on the training dataset, can continue to the future generations. this model constructs a tree made up of functions and variables and constants. the functions that were considered are the following: add, sub, multiplication, division, max, log, sqrt, and abs. the range of constants was from -1.5 to +1.5. the variables were also the same biochemical factors that were used in 3.1: cpk, ldh, potassium (k), and uric acid. 2.2. models on all data from the bam dataset one of the main difficulties for algorithms that are introduced in 2.1 is that data gathered from catastrophes usually have lots of missing information and the aforementioned algorithms in 2.1 do not work well with missing data, especially if all of these missing data were to be replaced with the mean of the dataset, as it is usually done. here we introduce another method for replacing these missing data that works better than simply replacing them with the mean of dataset. for the models built in this section, a broader range of biochemical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e29 factors were considered. these factors are: creatinine on the first day, sgot, phosphate, cpk, ldh, wbc, plt, uric acid, na, k, ca, age, gender, and creatinine on the third day. the last factor is only used to train a model to try and predict the value of the creatinine on the third day and after that, all values of creatinine are dropped. 2.2.1 missing values for all factors except age and creatinine on the 3r d day, data collected from previous studies were employed and missing data were replaced with previously known values for healthy humans. the aforementioned values are listed in table 1. the missing values in these columns are replaced accordingly so that models will not be very dependent on the mean of the data they are being trained on and if some column is missing, they will try to act in a way that the aforementioned factor is fine and the model has to diagnose the patient based on other factors. it should also be mentioned that for other values that were not mentioned, we did use the mean of the training data set. for prediction of age, a neural network was used. there was also missing data regarding gender, but most of the time this information is available, even in catastrophes. so, the information of patients whose gender was unknown were dropped. the number of these patients was less than 40 in 1440 patients. in order to predict the value of creatinine on the third day, another neural network was used, whether or not the information was available, because in real situations this information is usually not available and after the model was trained on the values of the patients whose information was available, all information of creatinine on the third day was dropped and then that value was predicted for everyone and then the next parts of the study were proceeded with. 2.2.2 neural network a multi-layer perceptron neural network was constructed to predict aki. this neural network is trained to penalize wrong outputs for patients who are diagnosed with aki. the aforementioned training procedure might result in overfitting, so a regularization algorithm called dropout was also used during the training. dropout can prevent overfitting as discussed in the work of srivastava et al. (9). the loss function in this model is very similar to cross entropy for binary classification: "loss" (y,y j )=-(w_1 y log(y j )+w_2 (1-y) log(1-y j ) ), where the values of w_1 and w_2 are equal to 2.8 and 0.07, respectively. 2.2.3 random forest decision trees are often used in medical applications because they can easily be implemented into dsss. these models try to choose one biochemical factor at each step to separate the data set, and this procedure is continued until the data set is separated into the target classes. in a random table 1: replacement of missing values with normal values for healthy humans variable value for males value for females cpk (iu/l) 57.5 40 sodium (meq/l) 140 140 potassium (meq/l) 4.75 4.75 calcium (meq/l) 9.5083 9.475 ldh (iu/l) 219 219 uric acid (mg/dl) 5.2 4.2 plt (/mm3 ) 350000 350000 wbc (/mm3 ) 7400 7400 cpk: creatine phosphokinase; ldh: lactate dehydrogenase; plt: platelet; wbc: white blood cell. forest, a group of decision trees are trained in which a grid search is used to select the best number of estimators, or decision trees. the values that were considered for the number of estimators were selected from 1 to 2000. 2.2.4 support vector machine support vector machines (svms) are used to find the best hyperplane to separate data in order to classify them. this hyperplane is found in a manner that has maximum classification margin with data. in order to model the non-linear relations, a kernel is used to transform the space of our data to higher dimensions. grid search was also used for support vector machine part of the work, where the values of c were selected from [0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000,5000, 10000] and the values for gamma from: [1, 0.5,0.1, 0.05,0.01, 0.005, 0.001, 0.0005, 0.0001]. in order to better approximate the non-linearities, rbf kernel was used (10). 2.2.5 ensembled method different versions of ensemble were tested, and in the end, the outputs of the last four models were entered into a logistic regression unit in order to have the final prediction. 2.2.6 cross validation all of the models were validated using k-folds, in some cases, 5 was chosen as k and for others, 10 was chosen. using k-fold validation enables us to assess how the trained model is able to generalize on an independent dataset. this would help to flag problems like over-fitting or selection bias (11, 12). r 3. results the sensitivity and specificity of the implemented models are provided in table 2. in the first step, the model introduced in 2.1.1 was used to train on records that had all of the following biochemical factors: cpk, ldh, potassium, uric acid and the value of creatinine on the third day. this data is used to learn how to predict the value of creatinine on the third day. after this training procedure, this model is trained and tested on two different parts of the datasets, the first one is the same this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. poorsarvi tehrani and h. malek 4 figure 1: the architecture of the first model from available data (fc_nn). cpk: creatine phosphokinase; ldh: lactate dehydrogenase. table 2: specificity and sensitivity of different models (95% confidence interval) models phase specificity sensitivity rc-nn on part1 train 99.91 (97.95-99.93) 99.58 (97.62-100) test 99.37 (97.41-100) 100.00 (98.04-100) partial data fields rc-nn on part2 train 99.27 (96.92-100) 92.49 (90.13-94.84) test 99.51(97.16-100) 89.28 (86.93-91.63) neural network model train 99.42 (97.26-100) 97.04 (94.88-99.19) test 99.37 (97.21-100) 96.57 (94.41-98.72) genetic programming train 99.51 (96.76-100) 90.53 (87.77-93.25) test 98.00 (95.26-99.65) 91.47 (88.72-94.21) neural network model train 93.54 (91.77-95.30) 100.00 (98.23-100) test 93.04 (91.27-94.80) 94.44 (92.67-96.21) random forest train 100.00 (97.35-100) 100.00 (97.15-100) test 99.24 (96.59-100) 90.24 (87.40-93.08) all data fields support vector machine train 99.84 (97.64-100) 89.64 (87.44-91.83) test 99.69 (97.49-100) 83.12 (80.92-85.31) random forest train 99.98 (97.59-100) 100 (97.61-100) test 99.47 (96.82-100) 89.20 (86.55-91.84) support vector machine train 99.84 (97.64-100) 90.49 (88.29-92.68) test 99.62 (97.42-100) 84.13 (81.93-86.32) ensembled train 99.89 (98.32-100) 96.58 (95.01-98.15) test 99.54 (97.97-100) 90.21 (88.64-91.78) as the one used to learn how to predict the value of creatinine on the third day, and the second one is the part of the dataset, which has the biochemical factors: cpk, ldh, potassium and uric acid. as you can see, the model’s accuracy will decrease a lot in the second part, because a lot of the data has been removed and the first part of this model has only been trained on 162 records so it has a generalization problem. this problem is solved in 2.2 when almost all of the data is used and the accuracy is higher. in the neural network model, a procedure is proposed to predict the state of a patient using the information from the value of creatinine on the third day. in comparison to the previous work of najafi et al. (6), which used a threshold for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e29 diagnosing the state of a patient, in the proposed method, a neural network is employed. this model is trained on the real values of creatinine and only tries to predict the state of a patient and does not regress the value of creatinine. the genetic programming (gp) model introduced in 2.1.3 uses the part of the dataset, which includes data about the following biochemical factors: cpk, ldh, potassium, and uric acid. it has 239 rows with 4 columns. the best formula that was derived from this model was the following: output = log (k)* max[0.613,max(k,uricacid)*ldh] in models built on all data samples, k-fold was used for validation, with k=10. as mentioned before, all of the collected information about the value of creatinine on the third day was dropped after the models learned how to predict it themselves. 4. discussion in this paper, different machine learning models were introduced for predicting aki in catastrophic events. in comparison to the previous work of najafi et al. (6) on this dataset, the models yielded higher sensitivity and specificity for prediction of aki on day 3. the models show their strength in different scenarios. random forests are made up from decision trees, which are easier to interpret in comparison with neural networks that act like black boxes, but as evident in the results, neural networks perform better than random forests. support vector machines are also easier to implement into dss but have more performance issues. overall, the best specificity that was achieved on testing almost all of the records was 99.24% and the best sensitivity that was achieved in testing almost all of the records was 94.44%. overall, neural networks have more robust results and given that they can be trained on more data to gain better accuracy, and gain more generalization, they show promising results. 5. limitations some of the best results achieved in this work are from nonlinear models like neural networks. when complex nonlinear models, relative to the amount of data available. are employed, the potential for overfitting of the model to the training data is high. although various methods have been used to solve the problem of overfitting, it seems that linear models can still be a better option, especially in situations where explainability is important. 6. conclusion in this article, we introduced several machine learning-based methods for predicting aki on the third day after a catastrophic incident. the introduced models show higher accuracy compared to previous works performed on the bam earthquake dataset. in the proposed models, an attempt was made to maintain the generalizability of the models by considering the missing data and replacing them with appropriate values, as well as using various regularization and validation methods such as dropout and cross-validation. due to the variety of models, it is possible to use each of these models in different conditions and for different applications. 7. declarations 7.1. conflict of interest the authors have no conflicts of interest to declare. 7.2. acknowledgment not applicable. 7.3. authors’ contributions all authors passed the criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.4. funding and supports nothing to declare references 1. ito j, fukagawa m. predicting the risk of acute kidney injury in earthquake victims. nature clinical practice nephrology. 2009;5(2):64-5. 2. aronson s, fontes ml, miao y, mangano dt. risk index for perioperative renal dysfunction/failure. circulation. 2007;115(6):733-42. 3. mehran r, aymong ed, nikolsky e, lasic z, iakovou i, fahy m, et al. a simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. journal of the american college of cardiology. 2004;44(7):1393-9. 4. wijeysundera dn, karkouti k, dupuis j-y, rao v, chan ct, granton jt, et al. derivation and validation of a simplified predictive index for renal replacement therapy after cardiac surgery. jama. 2007;297(16):1801-9. 5. palomba h, de castro i, neto a, lage s, yu l. acute kidney injury prediction following elective cardiac surgery: akics score. kidney international. 2007;72(5):624-31. 6. najafi i, van biesen w, sharifi a, hoseini m, rashid farokhi f, sanadgol h, et al. early detection of patients at high risk for acute kidney injury during disasters: development of a scoring system based on the bam earthquake experience. j nephrology. 2008;21(5):776-82. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. poorsarvi tehrani and h. malek 6 7. keras: the python deep learning api [available from: https://keras.io/. 8. abadi m, agarwal a, barham p, brevdo e, chen z, citro c, et al. tensorflow: large-scale machine learning on heterogeneous distributed systems. arxiv: 160304467. 2016. 9. srivastava n, hinton g, krizhevsky a, sutskever i, salakhutdinov r. dropout: a simple way to prevent neural networks from overfitting. the journal of machine learning research. 2014;15(1):1929-58. 10. wang j, chen q, chen y, editors. rbf kernel based support vector machine with universal approximation and its application. international symposium on neural networks; 2004: springer. 11. ioffe s, szegedy c. batch normalization: accelerating deep network training by reducing internal covariate shift. arxiv e-prints. 2015. 12. lazic s. the elements of statistical learning: data mining, inference, and prediction, 2nd edn. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e45 ca s e re p o rt acute myocardial infarction following naltrexone consumption; a case report bita dadpour1,2, arash gholoobi3, shahrad tajoddini4∗, amir habibi1 1. addiction research centre, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 2. cardiac anesthesia research centre, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 3. atherosclerosis prevention research center, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 4. neuroscience research center, institute of neuropharmacology, kerman university of medical sciences, kerman, iran. received: july 2016; accepted: july 2016; published online: 14 january 2017 abstract: cardiovascular effects of opioid withdrawal have long been studied. it was reported that patients with underlying ischemic heart disease and atherosclerotic vessels may be complicated by a sudden physical and emotional stress due to withdrawal syndrome. but some other believes sudden increase in catecholamine level as a sympathetic overflow might effect on heart with and without underlying ischemia. in the current study, a patient on methadone maintenance therapy (mmt) who experienced myocardial infarction (mi) after taking naltrexone was described. keywords: naltrexone, myocardial infarction, substance withdrawal syndrome, narcotic antagonists, case report © copyright (2017) shahid beheshti university of medical sciences cite this article as: dadpour b, gholoobi a, tajoddini sh, habibi a. acute myocardial infarction following naltrexone consumption; a case report. emergency. 2017; 5 (1): e45. 1. introduction cardiovascular effects of opioid withdrawal have long been studied. opioid withdrawal induces agitation, muscular pain, vomiting, diaphoresis, rhinorrhea, mydriasis as well as tachycardia and hypertension, which could be related to a transient increase in catecholamines. older patients with underlying cardiac ischemia could be at greater risk for cardiac events following abrupt withdrawal (1, 2); although this issue has been challenged (3). it was reported that patients with underlying ischemic heart disease and atherosclerotic vessels may be complicated by a sudden physical and emotional stress due to withdrawal syndrome. but some other believes sudden increase in catecholamine level as a sympathetic overflow might effect on heart with and without underlying ischemia. in the current study, a patient on methadone maintenance therapy (mmt) who experienced myocardial infarction (mi) after taking naltrexone was described. ∗corresponding author: shahrad tajoddini; neuroscience research center, institute of neuropharmacology, kerman university of medical sciences, kerman, iran. tel:00989133983682; email: tajadinishahrad@gmail.com 2. case presentation: a 64-year-old man was admitted in emergency toxicology ward with altered mental status and agitation. his symptoms were started abruptly following consumption of naltrexone and were progressed to respiratory distress and tachypnea. on medical history, he was diabetic and hypertensive. he was also on regular consumption of methadone (40 milligram daily) for recent 4 years following 20 years opium addiction. he had blood pressure 170/110 mmhg, heart rate: 90/minute, respiratory rate 24/minute, tympanic temperature 36.8◦c, and serum blood sugar 504 mg/dl on arrival. due to decreased level of consciousness and to maintain the airway, he was intubated and underwent mechanical ventilation. electrocardiography (ecg) on admission revealed old silent inferolateral myocardial infarction (mi) that showed in figure 1. intravenous nitroglycerin and regular insulin were administered for controlling high blood pressure and hyperglycemia and he was admitted in intensive care unit (icu). after a while, his blood pressure reached to 200/150 mmhg and dynamic changes were occurred on the ecg as revealed in figure 2, that illustrate an acute inferior myocardial infarction associated with positive troponin-i level. bedside echocardiography revealed global hypokinesis along this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. dadpour et al. 2 figure 1: brain magnetic resonance imaging (mri) and cerebral resonance angiography. figure 2: axial and coronal section cut of chest angiogram. with akinesis in apex and inferior wall and severe hypokinesis in inferior septal and anteroseptal wall. left ventricular ejection fraction reported as 30-35%. systolic pulmonary arterial pressure reported 30 mmhg and no pericardial effusion was detected. unfortunately, percutaneous coronary intervention was not accessible, so medical treatment for acute coronary syndrome was started based on recommendations of cardiologist consult. he was referred to cardiology ward in day 15 for further work up, where coronary angiography was performed and revealed three vessel diseases. he underwent coronary artery bypass grafting (cabg) on day 16 and finally was discharged after 27 days with recommendation to related cardiologic follow up in outpatient clinic. 3. discussion: potential relationship between opioids and coronary artery diseases has been widely studies in humans and animals (46). opioid induced manifestation on coronary artery disease (cad) is controversial and ranges from protective effects to triggering role in patients with coronary artery disease (1). it was reported that opium consumption may be positively correlated with the risk of cad in diabetic opium addict subjects undergoing coronary angiography. this effect was dose dependent (7). abrupt discontinuation of opioids or consumption of opioid antagonists in addict subjects lead to opioid withdrawal syndrome. this syndrome is considered to be a true physical stress and presented with agitation, severe muscular pain, vomiting, diaphoresis, rhinorrhea and mydriasis. a transient increase in catecholamines may also cause tachypnea, tachycardia and hypertension, which has been described as an overshoot phenomenon (8, 9). altered mental status might also occur. naltrexone, µand k-receptor antagonist, with a half-life of 10 hours could induce withdrawal symptoms if administered in opioid dependent cases. clinical manifestations of withdrawal syndrome usually appear within five minutes after consumption of naltrexone. (10). catecholamine release could lead to myocardial stunning and impaired perfusion of coronary flow reserve (11). reduced subendocardial perfusion, pulmonary edema and cardiac arrhythmias are being reported to be related to catecholamine release in opioid withdrawal (12, 13). increased noradrenergic and dopaminergic activity and consequent effects on heart following opium antagonist agents administration to morphine-dependent subjects has also been described in previous animal researches (14-16). potential mechanisms could be as follows: decrease in coronary flow reserve; microvascular dysfunction; direct effects of catecholamines on cardiac myocytes through calcium overload mediated by cyclic amp; oxygen-derived free radicals; contraction band necrosis which is an interstitial mononuclear inflammatory response; thrombosis formation in context of atherosclerotic vessels; increased blood pressure and ventricular contractility (17-19). this case report describes a methadone addict individual with underlying ischemic heart disease who experienced mi following naltrexone consumption. mi occurred in early phase of withdrawal syndrome. naltrexone induced physical and emotional stress in a patient on mmt may cause acute coronary syndrome in a patient with underlying ischemic heart disease. naltrexone should never be prescribed to an opioid addict; if happens, severe withdrawal syndrome will occur (8, 9). opioid addict cases on mmt and their family should be educated for this serious complication. it is recommended that naltrexone should be used 10 to 14 days after the last dose of methadone or at least 7 to 10 days after opium discontinuation (20-22). 4. appendix 4.1. acknowledgements we should appreciate of all kind attempts of toxicology icu staff in imam reza hospital. 4.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest none. 4.4. funding none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e45 references 1. schwartz bg, mayeda gs, burstein s, economides c, kloner ra. when and why do heart attacks occur? cardiovascular triggers and their potential role. hospital practice. 2010;38(3):144-52. 2. ramadan r, sheps d, esteves f, zafari am, bremner jd, vaccarino v, et al. myocardial ischemia during mental stress: role of coronary artery disease burden and vasomotion. journal of the american heart association. 2013;2(5):e000321. 3. masoomi m, zare j, nasri h, mirzazadeh a, sheikhvatan m. abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction. journal of cardiovascular medicine. 2011;12(4):234-8. 4. gross er, hsu ak, gross gj. opioid-induced cardioprotection occurs via glycogen synthase kinase β inhibition during reperfusion in intact rat hearts. circulation research. 2004;94(7):960-6. 5. marmor m, penn a, widmer k, levin ri, maslansky r. coronary artery disease and opioid use. the american journal of cardiology. 2004;93(10):1295-7. 6. gross er, hsu ak, gross gj. acute methadone treatment reduces myocardial infarct size via the δ-opioid receptor in rats during reperfusion. anesthesia and analgesia. 2009;109(5):1395. 7. hosseini sk, masoudkabir f, vasheghani-farahani a, alipour-parsa s, fathollahi ms, rahimi-foroushani a, et al. opium consumption and coronary atherosclerosis in diabetic patients: a propensity score-matched study. planta medica. 2011;77(17):1870-5. 8. hassanian-moghaddam h, afzali s, pooya a. withdrawal syndrome caused by naltrexone in opioid abusers. human & experimental toxicology. 2014;33(6):561-7. 9. sabzghabaee am, eizadi-mood n, gheshlaghi f, javani a, shirani s, aghaabdollahian s. role of benzodiazepines in the management of agitation due to inappropriate use of naltrexone. iranian journal of nursing and midwifery research. 2012;17(5):365. 10. schuckit ma. treatment of opioid-use disorders. new england journal of medicine. 2016;375(4):357-68. 11. nathaniel c. recurrent stress-induced cardiomyopathy: a case report and review article. case reports in medicine. 2011;2011. 12. reece as, hulse gk. elevation of central arterial stiffness and vascular ageing in opiate withdrawal: crosssectional and longitudinal studies. cardiovascular toxicology. 2013;13(1):55-67. 13. van dorp el, yassen a, dahan a. naloxone treatment in opioid addiction: the risks and benefits. expert opinion on drug safety. 2007;6(2):125-32. 14. fuertes g, laorden ml, milanes mv. noradrenergic and dopaminergic activity in the hypothalamic paraventricular nucleus after naloxone-induced morphine withdrawal. neuroendocrinology. 2000;71(1):60-7. 15. milanes m, fuente t, laorden m. catecholaminergic activity and 3’, 5’-cyclic adenosine monophosphate levels in heart right ventricle after naloxone induced withdrawal. naunyn-schmiedeberg’s archives of pharmacology. 2000;361(1):61-6. 16. laorden ml, fuertes g, gonzalez-cuello a, milanes mv. changes in catecholaminergic pathways innervating paraventricular nucleus and pituitary-adrenal axis response during morphine dependence: implication of α1-and α2-adrenoceptors. journal of pharmacology and experimental therapeutics. 2000;293(2):578-84. 17. wittstein is. stress cardiomyopathy: a syndrome of catecholamine-mediated myocardial stunning? cellular and molecular neurobiology. 2012;32(5):847-57. 18. wittstein is, thiemann dr, lima ja, baughman kl, schulman sp, gerstenblith g, et al. neurohumoral features of myocardial stunning due to sudden emotional stress. new england journal of medicine. 2005;352(6):539-48. 19. bybee ka, prasad a. stress-related cardiomyopathy syndromes. circulation. 2008;118(4):397-409. 20. boyce s, armstrong p, stevenson j. effect of innappropriate naltrexone use in a heroin misuser. emergency medicine journal. 2003;20(4):381-2. 21. adi y, juarez-garcia a, wang d, jowett s, frew e, day e, et al. oral naltrexone as a treatment for relapse prevention in formerly opioid-dependent drug users: a systematic review and economic evaluation. 2007. 22. kleber hd. pharmacologic treatments for heroin and cocaine dependence. the american journal on addictions. 2003;12(s2):s5-s18. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 24 emergency (2013); 1 (1): 24-26 brief report report of 267 cases of scorpion bite referring to an emergency department during one year mohammad manouchehrifar1*, shaghayegh khosravi2, ali khavanin2, niloufar derakhshandeh2 1. department of emergency medicine, haftome tir hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, golestan hospital, ahwaz university of medical sciences, ahwaz, iran abstract scorpion bite is a common health problem in many parts of the world, including the iran’s tropics. there are thousands of cases and a number of deaths due to scorpion bite every year in the country. the present study aims to provide further data regarding the details, complications and outcomes of scorpion bite cases referring to razi hospital, ahwaz, from march 2011 to april 2012. 267 patients (56.3% females) with a mean age of 35.2±15.8 years were included in the study. the most common genus of scorpion involved was hemiscorpius (69.3%) and the most frequent body part involved was the lower limb (38.9%). the frequency of hemolysis-induced renal insufficiency and death after scorpion bite were 1.9% and 1.1%, respectively. of all the factors evaluated in this series only the old age was associated with higher possibility of renal insufficiency (p<0.001). key words: bites and stings; scorpion, hemolysis; environmental; poisoning cite this article as: manouchehrifar m, khosravi sh, khavanin a, derakhshandeh n. report of 267 cases of scorpion bite referring to an emergency department during one year. emergency. 2013;1(1):24-6. introduction:1 corpion bite is a common health problem all over the world, including the iran’s tropics (1, 2). in iran, khouzistan and hormozgan provinces are regions with a lot of scorpions and there are thousands of reports each year about scorpion bite with a number of related deaths (3). in rural areas of khouzistan scorpion envenomation is the fourth common cause of death (4). the scorpions in iran belong to three families, 18 genera, 29 species and 5 subspecies (5). one study in khouzistan reported mesobuthus, androctonus, and hemiscorpius are responsible for 89.1% of bites (6). of all these families scorpionidae and buthidae are the most important ones; in this context, hemiscorpius is responsible for 95% of deaths and androctonus crassicauda (black scorpion) is the most dangerous type (7, 8). considering what discussed above, it is necessary to increase the knowledge of the health and treatment system about the details of scorpion bite, complications and outcomes of patients in these regions. therefore, the present study aimed to report *corresponding author: mohammad manouchehrifar; department of emergency medicine, haftome tir hospital, shahre rey, iran, 1617763141 mobile phone: +989144145867; phone: +982188987705. email: arashmanouchehrifar@yahoo.com received: 15 october 2013; accepted: 15 november 2013 the characteristics of scorpion bite in patients referring to the emergency unit of a hospital in ahwaz city. methods: the present case series has evaluated the victims of scorpion bite, who had been hospitalized in razi hospital, ahwaz city, from march 2011 to april s table 1: details of scorpion bite victims  particulars number (%) location of incident city 196 (73.5%) village 71 (26.5%) scorpion family hemiscorpius lepturus 185 (69.3%) androctonus crassicauda 26 (9.7%) mesobuthus eupeus 3 (1.1%) not known 53 (19.9%) the body part involved head and neck 31 (12.1%) trunk 33 (12.8%) abdomen 1 (0.4%) upper limb 88 (34.2%) lower limb 100 (38.9%) multiple 4 (1.6%) mailto:arashmanouchehrifar@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 25 manouchehrifar et al. 2012. data collected from the patients files, retrospectively, consisted of age, gender, location of the incident, the body part involved, the type of the scorpion involved, duration of hospitalization, clinical symptoms and signs, laboratory findings, type of the treatment rendered and patients’ status at discharge. data was registered in the database designed to this end and analyzed with spss 18. after providing a descriptive analysis, to examine the relationship between variables chi-square test was used. p value < 0.05 was considered as significant. patients: during the period of study, 267 patients (56.3% females) were referred to the emergency unit due to scorpion bite. the mean age of the patients was 35.2±15.8 years (range: 14-86). table 1 presents details about the incidents. the most common type of scorpion involved was hemiscorpius (69.3%). 188 (73.1%) bites had occurred in limbs (lower limb, 38.9% and upper limb, 34.2%) and only four (1.6%) patients had been received multiple bites in the limbs and trunk. the patients had been hospitalized for a mean period of 3.0±1.5 days (range: 1-11). 22 patients had been hospitalized to the intensive care unit (icu) for a mean period of 4.3±2.2 days. 76 (28.4%) patients simultaneously had a positive urinary test tape and a urinary rbc≤ 5/mm2, as an indicator of hemoglobinuria. finally, five (1.9%) patients had suffered from hemolysis-induced acute renal insufficiency during the hospitalization period and three (1.1%) of them had required dialysis (tables 2 and 3). no significant relationship was found between the type of involved scorpion and the chances of hemolysis and incidence of hemoglobinuria and renal insufficiency (p>0.05). in addition, of the factors of age, gender, the body part involved, anemia and leukocytosis, only age had a significant relationship with renal insufficiency (p<0.001). finally, eight patients had required injection of blood products after hemodialysis. all the patients table 2: demographic data of patients with acute renal insufficiency  variables cases 1 2 3 4 5 sex female female male female male age 28 19 30 79 86 location city city city village village involved body part upper limb lower limb trunk lower limb head and neck scorpion family hemiscorpius not known hemiscorpius androctonus hemiscorpius hospitalization (days) 7 1 6 5 4 icu1 (days) 5 1 6 5 4 need for dialysis + + + need for blood + anti-venom + + + + + outcome death discharge discharge death death 1 intensive care unit table 3: details of laboratory results of patients with acute renal insufficiency  laboratory tests cases 1 2 3 4 5 urine protein (mg/dl) 3 0 0 0 1 urinary wbc1 (1 /mm3) 10 2 12 42 60 urinary rbc2 (1/mm3) 6 2 4 12 8 hematuria 4+ 1+ 1+ 3+ 3+ creatinine (mg/dl) 3.1 1.7 1.7 2.3 1.8 bun3 (mg/dl) 164 19 17 28 16 platelet (×1000) 103 203 169 105 98 ptt4 (/second) 37 31 43 52 58 pt5 (/second) 18 12 12 17 17 wbc (/mm3) 24.3 14.9 5.2 17.8 19.1 hemoglobin (mg/dl) 7.9 8.2 11.6 9.8 9.2 1 white blood cell; 2 red blood cell; 3 blood urea nitrogen; 4 partial thromboplastin time; 5 prothrombin time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 26 emergency (2013); 1 (1): 24-26 had received anti-venom and 50.7% antibiotics and 43.6% corticosteroids. finally, 245 patients (91.8%) had been discharged without any specific complications and three (1.1%) died. 19 (7.1%) patients had left the hospital against medical advice before completion of diagnostic and therapeutic procedures. discussion: the most common type of scorpion in these series was hemiscorpius and the most common body part was the lower limb. the frequency of renal insufficiency and mortality due to the scorpion bites were 1.9% and 1.1%, respectively. of all the factors evaluated in this study, only the old age was associated with a higher incidence of renal insufficiency. of course, it should be pointed out that sufficient data was not available in relation to other possible concomitant diseases in these victims. the mean ages of victims reported did not the same in different studies (9-12). given the fact that hospital evaluation in the present study admits only adult patients, the mean age of 35 years seems to be acceptable. in terms of sex distribution, location of the bite, and the mortality rate this study is consistent with pervious one(4, 13). preparation and implementation of an educational program to increase people’s awareness about the importance and the necessity of attention to scorpion bite might help decrease the incidence. it appears that some precautions can decrease the number of scorpion bite cases, including repairing and closing cracks and splits in buildings, keeping wood logs and chips, and motes away from homes and rural residential areas as well as avoiding sleeping outdoors. acknowledgement: the authors would like to thank all the colleagues who helped in different stages of the present study, from data collection to preparation of the report. conflict of interest: none funding: none author’s contribution: all authors have substantial contribution in designing, data gathering and analysis, revising and final approving of the published version and are responsible for all aspects of the work. references: 1. world health organization. rabies and envenoming, report consultative meeting. geneva: world health organization; 2007. 2. mohseni a, vazirianzadeh b, hossienzadeh m, salehcheh m, moradi a, moravvej sa. the roles of some scorpions, hemiscorpius lepturus and androctonus crassicauda, in a scorpionism focus in ramhormorz, southwestern iran. j insect sci. 2013; 13:1-12. 3. labafgahsemi r. status of scorpion stings in iran and their prevention. behvarz journal. 1999; 2(10): 32-5. [persian]. 4. meashk z, nemat r, mahboubian n. the epidemiology of scorpionism in the patients admitted in scorpion ward of aboozar hospital, ahvaz; 1989-1990. hakim. 2000;3(3): 215-22. [persian]. 5. dehghani r, valaie n. classification of scorpions and their diagnostic clue. kaums journal (feyz). 2005;8(4): 73-92. [persian]. 6. vazirianzadeh b, haji hr, amri b, bageri s, molaei seyedeh m. epidemiological study of scorpionism in the hospitals of ahvaz, sw iran, 2nd six months of 2006. j health sci. 2010;2(2):17-25 [persian]. 7. zargan j, tirgari s, tahernejad k, lotfi h, farahmandzad a. study of scorpion fauna in abomosa, great & small tonbs and hengam islands of the persian gulf. iran south med j. 2003;6(1):20-4. [persian]. 8. akbari a, tabatabai m, hedayat a, modiroosta h, alizadeh m, zare mk. study of the geographical distribution of scorpions in the south of iran. j pajo sazandegi. 1997;34:112-5. [persian]. 9. attamo h, diawara n, garba a. epidemiology of scorpion envenomations in the pediatric service of the agadez hospital center (niger) in 1999. b soc pathol exot. 2002;95(3):209-11. [french]. 10. jarrar bm, al-rowaily ma. epidemiological aspects of scorpion stings in al-jouf province, saudi arabia. ann saudi med. 2008;28(3):183-7. 11. charrab n, soulaymani a, mokhtari a, soulaymani r. scorpion envenomation treated at beni mellal provincial hospital in morocco. revue méd trop. 2009;69(1):33-6. 12. al-asmari ak, al-saif aa. scorpion sting syndrome in a general hospital in saudi arabia. saudi med j. 2004;25(1): 64-70. [persian]. 13. dehghani r. thermotherapy in the treatment of hemiscorpius lepturus. tehran: health college, tehran university of medical sciences; 2000. archives of academic emergency medicine. 2021; 9(1): e41 or i g i n a l re s e a rc h is social distancing policy effective in controlling covid19? an interrupted time series analysis mehdi yaseri1, rahim soleimani-jelodar2, zohreh rostami3, saeed shahsavari1∗, mostafa hosseini1 † 1. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 2. department of virology, school of public health, tehran university of medical sciences, tehran, iran. 3. department of accounting, qazvin branch, islamic azad university, qazvin, iran. received: march 2021; accepted: april 2021; published online: 25 may 2021 abstract: introduction: the social distancing plan is one of the ways that was implemented for management of covid19 pandemic. this study aimed to evaluate the effect of the social distancing on reducing the daily new cases and deaths from covid-19. methods: in this cross-sectional study, the data of daily new cases and daily deaths were collected from 15/02/2020 to 19/04/2020. changes in the level and trend of daily new cases and daily deaths before and after the implementation of social distancing plan were evaluated using interrupted time series (its) analysis in stata software. results: the post-intervention trend had a decrease of 102 new cases per day and 7 new deaths per day compared to the pre-intervention trend (p < 0.001). moreover, in the postintervention period, the daily new cases had a decrease of 58 new cases per day and 2 new deaths per day (p < 0.001). conclusion: it could be concluded that social distancing plan directly affects the new daily cases and new daily deaths. keywords: physical distancing; incidence; covid-19; interrupted time series analysis; iran cite this article as: yaseri m, soleimani-jelodar r, rostami z, shahsavari s, hosseini m. is social distancing policy effective in controlling covid-19? an interrupted time series analysis. arch acad emerg med. 2021; 9(1): e41. https://doi.org/10.22037/aaem.v9i1.1201. 1. introduction an outbreak of pneumonia with unknown etiology occurred in late december 2019, in wuhan city, china (1). on jan 12, 2020, the causative agent of wuhan pneumonia was temporarily called novel coronavirus-2019 (2019-ncov ) by the world health organization (who) and the resulting disease was named covid-19 (2). on 19 february 2020, iran reported its first confirmed cases of sars-cov-2 infection in qom. raoofi et al. reported the timeline of iran’s governance measures (figure 1) after the official declaration of the covid-19 epidemic in iran (3). social distancing plan is one of iran’s governance measures, which was implemented on 25 march, 2020. detailed data on the effectiveness of non∗corresponding author: saeed shahsavari; department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. postal code: 3419759811, e-mails: biostat93@gmail.com, orcid: https://orcid.org/0000-0002-0806-6026. † corresponding author: mostafa hosseini; department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. fax: +98 2833345862, mhossein110@yahoo.com, orcid: https://orcid.org/0000-0002-1334-246x. pharmaceutical interventions (npis) are still limited; therefore, conducting public health studies for studying their effect on covid-19 incidence is necessary. agarwal et al. studied covid-19 pandemic and its societal impact and found that race, culture, level of education, and socio-economic status have a major impact on disease outbreak (4). recently, pan et al. reported in jama, the epidemiological effects of npi implementation throughout the covid-19 epidemic in wuhan, and found that use of multidimensional npis had contributed to control of the covid-19 outbreak in wuhan (5). since, covid-19 outbreak is a serious threat to public health and healthcare personnel universally, it seems essential to control the burden of disease through adoption and implementation of proper policies including social distancing, isolation of covid-19 patients, and quarantine operation (6). the primary aim of social distancing plan in iran was to decrease the daily new cases and deaths due to covid-19 outbreak. it was expected to prevent the collapse of the healthcare system as happened in italy, spain, india, and united kingdom (7-9). based on the abovementioned points, this study aimed to evaluate the effect of the social distancing on reducing the number of daily new cases and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yaseri and et al. 2 deaths due to covid-19. 2. methods 2.1. design and study population this is a descriptive-analytical study, which has been performed longitudinally. we performed a quasi-experimental, interrupted time series (its), as a strong quasi-experimental design to detect immediate and longitudinal changes in covid-19 daily new cases and deaths in iran, before and after the social distancing plan. its was applied to evaluate the effects of health interventions, its is a powerful and increasingly popular design for evaluating public health interventions (10-13). however, it is difficult to fully account for all the biases that might have impacted the covid-19 daily new cases and deaths in iran in ways not related to social distancing policy. autocorrelation condition effect should also be considered when performing this plan: autocorrelation is usually present in the time series data and it is defined as the correlation between the response variable at time t and the response variable at times t-1 and t-2 (13). 2.2. data sources and data setting the daily new cases and deaths were obtained from governmental websites and european center for disease prevention and control between march 21 and april 20, 2020 (14). in the present study, the response variable was daily new cases and daily deaths, the explanatory variable was time (setting day 1 as the first covid-19 diagnosed case), the intervention variable was social distancing plan in iran, which was carried out on 25 may 2019 (setting 0 as the period without social distancing between february 15 and march 28, 2020 and 1 as the period with social distancing between march 29 and april 19, 2020) and interaction between time and social distancing plan. 2.3. statistical methods we applied its analysis to assess both the immediate-level changes as well as changes in the trend of the daily new cases and deaths before and after the intervention. moreover, we created the scatter plot of new daily cases and new deaths over time to visually inspect our data and examine whether there was a social distancing plan effect. autocorrelation was evaluated through visual detection of the plot of the residuals vs. time, using durbin-watson test (15). p-value less than 0.05 was considered to indicate statistical significance. stata version 14 was used for our data analysis. the segmented regression models are fitted in the form of the leastsquares regression line. it is assumed that there is a linear relationship between the time and the response variable inside each segment (11). 3. results the impact of the social distancing plan on daily new cases in iran was reduction in both new daily cases and new death rates. 3.1. the impact of social distancing plan on daily new cases the results of segmented regression for the response variable of daily new cases demonstrated that daily changes in the number of new cases were significant compared to before implicating social distancing plan (coef. = 43.6, 95%ci: 36.7 50.6; p <0.001). furthermore, on the day after the intervention, an increase of 1478 cases was observed in the number of new cases (coef.= 1478.8, 95%ci: 1132.9 – 1824.8; p<0.001). the post-intervention new cases trend had displayed a decrease of 102 cases per day compared to the pre-intervention trend (coef.= -102.4, 95%ci: -116.4 – -88.3; p<0.001). moreover, after the intervention, daily new cases had a decrease of 58 cases per day (coef.= -58.7, 95%ci: -70.4 – -46.9; p<0.001). figure 2 displays the distribution of covid-19 daily new cases in iran before and after the implementation of social distancing plan from february 15, 2020 to may 3, 2020. 3.2. the impact of social distancing plan on daily new deaths the results of segmented regression for the impact of social distancing plan on daily new deaths in iran demonstrated that daily changes in the new deaths were statistically significant compared to before the social distancing plan implementation (coef.= 4.8, 95%ci: 3.9 – 5.7; p<0.001). on the next day after the intervention, an increase of about 8 cases was observed in new deaths, which was not significant (coef.= 7.9, 95%ci: -13.9 – 29.9; p=0.471). the post-intervention new deaths trend showed a decrease of 7 cases per day (compared to the pre-intervention trend). decrease in the rate of new deaths after intervention was significant (coef.= -7.2, 95%ci: -8.1 – -6.2; p<0.001). moreover, after the intervention, the daily new deaths had a decrease of 2 cases per day, which was statistically significant (coef.= -2.3, 95%ci: -2.6 – -1.9; p<0.001). figure 2 displays the distribution of covid19 daily deaths in iran before and after the social distancing plan implementation. 4. discussion this study was conducted to answer this question: was social distancing policy effective in controlling covid-19 in iran? results of an interrupted time series analysis proved that social distancing plan was significantly effective in reducing the total number of the new daily cases and the new deaths in iran. as depicted in the results section, daily change in the number of new cases and new deaths was increasing before this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e41 the implementation of social distancing plan. furthermore, the trend of daily new cases after the intervention displayed a decrease of 102 cases per day. also, the trend of new death cases showed a decrease of 7 case per day, on average (compared to the pre-intervention trend). the reasons for this achievement can be the implementation of social distancing as well as the increase in the knowledge levels of individuals. therefore, social distancing plan seems to be effective in reducing the spread of covid-19. the primary goal of social distancing plan is to reduce physical contact between individuals and prevent person-to-person spread of the disease (3). use of non-pharmaceutical public health interventions such as isolation, quarantine, social distancing, and community containment to control infectious disease outbreaks is effective enough to slow down the spread of the virus (2, 16). in a study by priyadarsini et al., social distancing was introduced as a key factor that could suppress the viral spread directly or indirectly (17). as demonstrated in the results section, social distancing plan implementation had a significant effect on the number of new daily cases and new death cases. there are several studies published in a short time span, indicating the importance of social distancing measures. the same finding has been reported in others’ researches, a study conducted by medeiros de figueiredo et al. (18), which had evaluated the impact of lockdown on covid19 incidence and mortality in chinese provinces (hubei and guangdong) using its model, showed that social distancing measures were effective in reducing the incidence and mortality rates. in another its model study by siedner et al. (19), the mean daily covid-19 growth rate decreased after implementation of the first statewide social distancing measures. it is essential to mention that although social distancing seems to have been effective in controlling covid-19 in iran, there are socio-economic challenges associated with this mechanism. since this plan closes some jobs and reduces working hours, it can lead to significant productivity losses in the economy in the long run. according to the global epidemic scenario, gross domestic product (gdp) can be reduced by 2.5 percent and 1.8 percent in developing countries and in industrialized countries, respectively (20). on the other hand, the closing of schools and the cessation of basic education can cause damage in terms of improving the level of basic knowledge in the long run. thus, many public policymakers may face the challenge of cost-effectiveness of social distancing policy. finding cost-effective mechanisms in controlling the disease was a key step before the coronavirus vaccine was discovered. as evident in the obtained results, the trend of new daily cases and new daily deaths was decreasing after the implantation of social distancing plan. therefore, it can be concluded that the social distancing plan directly affected the daily new cases and daily new deaths, resulting in a decline in the rates of covid-19 cases. furthermore, formulating appropriate policies, such as social distancing, and implementing them seem to be necessary to slow the spread of infection. thus, social distancing can be used as an effective strategy to save lives and slow the spread of covid-19. 5. limitations it should be noted that this study has some limitations. first, researchers had to use daily new cases data of the disease due to a lack of data on the incidence and prevalence. second, due to the lack of a comparable control group, the effect of intervening variables and other unobservable variables on the trend of new cases was not controlled. furthermore, the interrupted time series design defines a simple pre-post comparison that cannot provide information about the various mechanisms leading to the changes. 6. conclusion the results of our analysis showed that the trend of daily new cases of covid-19 and the resulting deaths was decreasing since the implementation of social distancing plan in iran. in other words, social distancing plan has been effective in controlling this disease. however, such a plan can lead to economic and social challenges. it is suggested that further studies examine the effectiveness of the social spacing scheme by controlling the intervening variables. studies on the costeffectiveness of this policy can also provide valuable insight regarding its usefulness. 7. declarations 7.1. acknowledgments the authors would like to thank all researchers and health professionals that are confronting the covid-19 pandemic. 7.2. author contribution my, ss and mh conceptualized the research idea, collected data, performed the analysis and wrote the first draft of the manuscript. rsj and zr contributed in the data acquisition, analysis, interpretation. all authors read and approved the final manuscript. 7.3. funding sources this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. 7.4. conflict of interest authors declared no conflict of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yaseri and et al. 4 references 1. gorbalenya ae. severe acute respiratory syndromerelated coronavirus–the species and its viruses, a statement of the coronavirus study group. biorxiv. 2020. 2. wilder-smith a, freedman d. isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-ncov ) outbreak. journal of travel medicine. 2020;27(2):taaa020. 3. raoofi a, takian a, sari aa, olyaeemanesh a, haghighi h, aarabi m. covid-19 pandemic and comparative health policy learning in iran. archives of iranian medicine. 2020;23(4):220. 4. prof. sunitha b k dva. covid – 19: current pandemic and its societal impact. international journal of advanced science and technology. 2020;29(5s):432 9. 5. pan a, liu l, wang c, guo h, hao x, wang q, et al. association of public health interventions with the epidemiology of the covid-19 outbreak in wuhan, china. jama. 2020. 6. nussbaumer-streit b, mayr v, dobrescu ai, chapman a, persad e, klerings i, et al. quarantine alone or in combination with other public health measures to control covid-19: a rapid review. cochrane database of systematic reviews. 2020(4). 7. busch c, ludwig a, santaeulàlia-llopis r. emerging evidence of a silver lining: a ridge walk to avoid an economic catastrophe in italy and spain. safe white paper, 2020. 8. thayer wm, hasan mz, sankhla p, gupta s. an interrupted time series analysis of the lockdown policies in india: a national-level analysis of covid-19 incidence. health policy and planning. 2021. 9. shah sa, quint jk, nwaru bi, sheikh a. impact of covid19 national lockdown on asthma exacerbations: interrupted time-series analysis of english primary care data. thorax. 2021. 10. kiani mm, tajvar m. analyzing normal delivery promotion policy in health system reform of iran: an application of kingdon multiple streams model. health_based research. 2018;3(4). 11. wagner ak, soumerai sb, zhang f, ross-degnan d. segmented regression analysis of interrupted time series studies in medication use research. journal of clinical pharmacy and therapeutics. 2002;27(4):299-309. 12. yakhforoshha a, emami sah, shahi f, shahsavari s, cheraghi m, mojtahedzadeh r, et al. effectiveness of integrating simulation with art-based teaching strategies on oncology fellows’ performance regarding breaking bad news. journal of cancer education. 2019;34(3):46371. 13. bernal jl, soumerai s, gasparrini a. a methodological framework for model selection in interrupted time series studies. journal of clinical epidemiology. 2018;103:82-91. 14. alamshahi m, olfati f, shahsavari s, taherpour m. the effectiveness of group counseling based on problemsolving on experiencing domestic violence among pregnant women: a clinical trial. social health and behavior. 2020;3(2):62. 15. hopewell s, ravaud p, baron g, boutron i. effect of editors’ implementation of consort guidelines on the reporting of abstracts in high impact medical journals: interrupted time series analysis. bmj. 2012;344:e4178. 16. kuper-smith bj, doppelhofer lm, oganian y, rosenblau g, korn c. optimistic beliefs about the personal impact of covid-19. 2020. 17. lakshmi priyadarsini s, suresh m. factors influencing the epidemiological characteristics of pandemic covid 19: a tism approach. international journal of healthcare management. 2020:1-10. 18. de figueiredo am, codina ad, moreira dc, figueiredo m, saez m, león ac. impact of lockdown on covid-19 incidence and mortality in china: an interrupted time series study. 2020. 19. siedner mj, harling g, reynolds z, gilbert rf, venkataramani a, tsai ac. social distancing to slow the u.s. covid-19 epidemic: an interrupted time-series analysis. medrxiv. 2020:2020.04.03.20052373. 20. maliszewska m ma, van der mensbrugghe d. the potential impact of covid-19 on gdp and trade: a preliminary assessment. policy research working paper. east asia and the pacific region office of the chief economist &macroeconomics, trade and investment global practice april 2020: 9211, 1-26. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e41 figure 1: chronological timeline of iran’s measures after covid-19 outbreak. figure 2: coronavirus daily new cases (left) and deaths (right) before and after the implementation of social distancing plan in iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e10 le t t e r to ed i to r piperonylbutoxide as a dubious cause of cardiac manifestations in pyrethroid insecticide poisoning; a letter to editor foroozan faress1, maryam ameri1, maryam vasheghani farahani2, sayed mahdi marashi1∗ 1. department of forensic medicine, school of medicine, iran university of medical sciences, tehran, iran. 2. department of forensic medicine, school of medicine, aja university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 cite this article as: faress f, ameri m, vasheghani farahani m, marashi sm. piperonylbutoxide as a dubious cause of cardiac manifestations in pyrethroid insecticide poisoning; a letter to editor. arch acad emerg med. 2023; 11(1): e10. https://doi.org/10.22037/aaem.v11i1.1848. dear editor; some of the articles on cypermethrin poisoning manifesting with cardiac problems, published in 2020 and 2021, have attracted our attention (1, 2). in one of these papers, a 70-year-old female was presented with acute exposure to insecticide spray containing cypermethrin, tetramethrin and piperonylbutoxide, showing dyspnea as well as considerable chest pain. based upon the preliminary evaluation of the patient, high-sensitivity troponin t increased within an hour; however, coronary artery disease was ruled out on coronary angiography. hence, non-st elevation myocardial infarction due to direct cardiotoxicity of cypermethrin was proposed as the reason (1). another paper presented an eighteen-year-old male with acute cypermethrin poisoning showing bradycardia at a range of 45-54 bpm and some premature ventricular complexes. the only medication prescribed, was atropine sulphate. after 48 hours of admission his heart rate steadily normalized (2). in discussion of each paper, the authors cite some reports of different types of heart block in the field of pyrethroid exposure, as well as positive association between urinary pyrethroid metabolites and cardiovascular involvement (3-5). as we know, cypermethrin is a synthetic pyrethroid used as an insecticide, which has neurotoxic properties in insects. resistance to pyrethroid compounds is not rare and considering its synergic effect, piperonylbutoxide is added to many pesticide products to increase their insecticidal potency (1). piperonylbutoxide has no insecticide effect itself (6). it is not ∗corresponding author: sayed mahdi marashi; department of forensic medicine and clinical toxicology, shohadaye haftom-e-tir hospital, end of shahid rajaee st., shahr ray, tehran, iran. e-mail: marashi.mh@iums.ac.ir, tel: +982155228596, orcid: https://orcid.org/0000-0001-7450-6379. sold as a commercial product in marketplace and it is usually ignored when clinicians are searching for ingredients of the insect killer product. however, it can lead to development of toxicological manifestations in humans if they are exposed to it. the only case for piperonylbutoxide toxicity in man was reported in 2000, and bradycardia was the main clinical manifestation (7). interestingly, in one case of thirddegree heart block discussed here, the pesticide formulation contained d-phenothrin, a pyrethroid, and piperonylbutoxide (2). however, in another case, no data regarding pesticide formulation is available (3). searching for more evidence, we found only three other case reports of cardiotoxicity after exposure to pesticide products, in which when formulation is available, and piperonylbutoxide is the definitive ingredient (4, 5, 8). the neuronal voltage-gated na+ channel is the main site of action for pyrethroids. they bind to the channel when it is open, which leads to prolonged inward sodium transfer and extended action potentials (6). by searching in reputable scientific databases, we couldn’t find any research about the cardiac effects of pyrethroid on mammalian heart; however, some studies were done on dichlorodiphenyltrichloroethane (ddt) (9). because pyrethroids and ddt both act by connecting to the same type of na+ channels (6), their cardiac effects can be expected to be similar. in their study on whether the heart of animals exposed to ddt is prone to develop dysrhythmia, jeyaratnam and forshaw have found no electrocardiogram abnormalities in living samples, and the contractility of isolated heart muscle was not altered either. yet, the administration of epinephrine caused unexpected bradycardia and dysrhythmia (9). interestingly, pyrethroid poisoning can cause stimulation of large-scale epinephrine and norepinephrine release, even in non-severe cases (10). we couldn’t find any evidence indithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index f. faress et al. 2 figure 1: it isn’t known whether pyrethroids produce a direct effect on the adrenal glands or they act through the stimulation of central nervous system to stimulate the release of norepinephrine and epinephrine. cating whether pyrethroids produce a direct effect on the adrenal glands or they act through the stimulation of central nervous system (figure 1). pyrethroids are metabolized in the body by cytochrome p450 enzymes. piperonylbutoxide has an inhibitory effect on this system (6), which causes a delay in elimination. accordingly, epinephrine release may continue in the prolonged presence of pyrethroid compound, and cardiac abnormalities are caused by the provisional interaction between the toxin and epinephrine (10). there is no well-proven scientific basis to conclude that the abovementioned case reports are biased in summarizing their articles. in conclusion, we think that pyrethroid poisoning may be seen with different faces, depending on the presence or absence of piperonylbutoxide in the commercial product. hence it is necessary for all clinical toxicologists to determine suspicious ingredients when they are facing a doubtful manifestation. 1. declarations 1.1. acknowledgments none declared. 1.2. conflict of interest no author of this paper has a conflict of interest, including specific financial interests to declare. 1.3. fundings and supports none. 1.4. authors’ contribution the authors meet the four criteria for authorship based on the icmje recommendations of medical journal editors. references 1. habedank d, stubbe b, ewert r, kroll a, atmowihardjo i, habedank b. inhalation of publicly available indoor insecticide spray caused myocardial infarction type ii: a case report. esc heart fail. 2021;8(4):3403-7. 2. shilpakar o, karki b. cypermethrin poisoning manifesting with prolonged bradycardia: a case report. toxicol rep. 2021;8:10-2. 3. alexandri m, spaeth kr. nontransient third-degree heart block and persistent respiratory findings as sequelae of acute occupational exposure to pyrethroids insecticide. am j ind med. 2020;63(7):644-8. 4. bhaskar em, moorthy s, ganeshwala g, abraham g. cardiac conduction disturbance due to prallethrin (pyrethroid) poisoning. j med toxicol. 2010;6(1):27-30. 5. singh h, luni fk, marwaha b, ali ss, alo m. transient complete heart block secondary to bed bug insecticide: a case of pyrethroid cardiac toxicity. cardiology. 2016;135(3):160-3. 6. hoffman rs, howland ma, lewin na, nelson ls, goldfrank lr. goldfrank’s toxicologic emergencies. 10th ed: mcgraw-hill new york; 2014. 7. babić g, jović-stošić j, todorović v, kosanović m, janković s. cardiotoxicity of piperonyl-butoxide: a case report. pesticidi. 2000;15(4):297-300. 8. walters jk, boswell le, green mk, heumann ma, karam le, morrissey bf, et al. pyrethrin and pyrethroid illnesses this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e10 in the pacific northwest: a five-year review. public health rep. 2009;124(1):149-59. 9. jeyaratnam j, forshaw p. a study of the cardiac effects of ddt in laboratory animals. bull world health organ. 1974;51(5):531. 10. krieger r, krieger wc. handbook of pesticide toxicology. massachusetts: academic press; 2001. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index declarations references archives of academic emergency medicine. 2021; 9(1): e27 https://doi.org/10.22037/aaem.v9i1.1108 or i g i n a l re s e a rc h platelet and haemostasis are the main targets in severe cases of covid-19 infection; a system biology study mona zamanian-azodi1, babak arjmand2, mohammadreza razzaghi3, mostafa rezaei tavirani1∗, alireza ahmadzadeh1, mohammad rostaminejad4 1. proteomics research center, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. cell therapy and regenerative medicine research center, endocrinology and metabolism molecular-cellular sciences institute, tehran university of medical sciences, tehran, iran. 3. laser application in medical sciences research center, shahid beheshti university of medical sciences, tehran, iran. 4. gastroenterology and liver diseases research center, research institute for gastroenterology and liver diseases, shahid beheshti university of medical sciences, tehran, iran. received: january 2021; accepted: february 2021; published online: 14 march 2021 abstract: introduction: many proteomics-based and bioinformatics-based efforts are made to detect the molecular mechanism of covid-19 infection. identification of the main protein targets and pathways of severe cases of covid-19 infection is the aim of this study. methods: published differentially expressed proteins were screened and the significant proteins were investigated via protein-protein interaction network using cytoscape software v. 3.7.2 and string database. the studied proteins were assessed via action map analysis to determine the relationship between individual proteins using cluepedia. the related biological terms were investigated using cluego and the terms were clustered and discussed. results: among the 35 queried proteins, six of them (fga, fgb, fgg, and fgl1 plus tln1 and thbs1) were identified as critical proteins. a total of 38 biological terms, clustered in 4 groups, were introduced as the affected terms. “platelet degranulation” and “hereditary factor i deficiency disease” were introduced as the main class of the terms disturbed by covid-19 virus. conclusion: it can be concluded that platelet damage and disturbed haemostasis could be the main targets in severe cases of coronavirus infection. it is vital to follow patients’ condition by examining the introduced critical differentially expressed proteins (deps). keywords: covid-19; proteins; bioinformatics; computational biology; network analysis cite this article as: zamanian-azodi m, arjmand b, razzaghi m, rezaei tavirani m, ahmadzadeh a, rostaminejad m. platelet and haemostasis are the main targets in severe cases of covid-19 infection; a system biology study. arch acad emerg med. 2021; 9(1): e27. 1. introduction covid-19 infection resulted in difficulties all over the world and for all the different races of human beings in all countries. in addition, it has imposed complex effects on patients’ lifestyle, which lead to manifestation of other conditions such as diabetes, cancers, and other types of disorders, and has thus attracted the attention of researchers and they want to solve this problem (1-3). since understanding the molecular mechanism of the diseases is fundamental in diagnosis and therapy of diseases, many efforts are made to study ∗corresponding author: mostafa rezaei tavirani; proteomics research center, faculty of paramedical sciences,darband street, tajrish square, tehran, iran. email: tavirany@yahoo.com, tel: 00989122650447, orcid:????????????? . the molecular aspect of covid-19 infection (4-6). proteomics and informatics are two suitable methods for finding the molecular mechanism of different kinds of diseases (7, 8). since proteomics is a high-throughput method, results of proteomics are reliable data that can be interpreted and analyzed via informatics (9, 10). network analysis based on graph theory is a method in bioinformatics, which is widely applied for evaluating diseases in medical sciences (11, 12). differentially expressed proteins (deps) bind to the other proteins based on affinity, and form a network of nodes, which are linked by edges (13). the constructed network contains useful information about the elements of the network (14). action map is another useful method for determining the relationship between the queried deps. possible inhibition, activation, reaction, binding, and regulation roles of a protein related to the neighbors can be identified via acthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. zamanian-azodi et al. 2 tion map analysis (15). gene ontology is another molecular analysis that can be used to detect the pathways and biological processes that are related to the studied proteins. many diseases are assessed via gene ontology method to find the critical dysregulated pathways and biological processes (16, 17). in the present study, deps of severe cases of covid-19 are extracted from a paper by ting shu et al. and are investigated via network analysis, action map assessment, and gene ontology examination. in the report of ting shu et al., plasma protein expression changes of patients in the cases of fatal, severe, and mild conditions are compared with the controls. here, the severe cases of covid-19 were selected to be assessed and their significant deps were investigated. 2. methods in this bioinformatics study, 35 differentially expressed proteins based on fold change ≥ 1.5 and p-value ≤ 0.01, which were identified by evaluating protein expressions in severe cases of covid-19 versus healthy people, were extracted from the paper published by ting shu et al. (18). the differentially expressed proteins were included in an interactome unit using “protein query” of string database via cytoscape software 3.7.2. the network including a main connected component and two isolated proteins was constructed. furthermore, to understand the type of interactions between the nodes, action map analysis was investigated. for this purpose, activation, inhibition, binding, and regulation actions were evaluated using cluepedia v1.5.7. the biological terms related to the 35 deps were investigated using cluego 2.5.7 from reactome_pathways_08.05.2020, clinvar_human-diseases_08.05.2020, kegg_08.05.2020, and wikipathways_08.05.2020. in the statistical analysis, protein expression values were determined based on mean value of data. kapa scoring was set to 0.4. additionally, term p value corrected with bonferroni step down, group p value, and group p value corrected with bonferroni step down were ≤ 0.01 in gene ontology analysis. the protocol of study was approved by ethics committee of shahid beheshti university of medical sciences, tehran, iran (ethics code: ir.sbmu.retech.rec.1399.355). 3. results except for arhgdib and sh3bgrl3 the other deps were included in the network by undirected edges. as shown in figure 1, a compacted region, which is mainly formed by various types of fibrinogen chains, has appeared as a central part of the constructed network. this finding is confirmed by action map (see figure 2). fga, fgb, fgg, and fgl1 plus tln1 and thbs1 are connected together in action map. ywhaz, ywhae, and cfl1 that are located in figure 1, formed a triple unit in the action map. since the network is not a scale free type, centrality analysis was not applied to find the central nodes such as hubs or bottlenecks. a total of 38 biological terms related to the 35 deps are shown in figure 3 and table 1. the terms are grouped in four classes. the smallest group includes only one term (translocation of slc2a4 (glut4) to the plasma membrane), while hereditary factor i deficiency disease, as the largest group, includes 29 terms. frequency of groups of terms is represented in figure 4. 4. discussion efforts of researchers to solve covid-19 infection problems led to production of large numbers of publications. proteomics and bioinformatics are two powerful methods that have been frequently applied in molecular studies of covid19 (19, 20). in the present study, bioinformatics evaluation of plasma proteome of patients with severe covid-19 revealed a new perspective of the disease. as shown in figure 1, a total of 35 significant deps are connected as an interactome unit to create a new concept about covid-19 pandemic. apart from two proteins, the other deps are interacted in a heterogeneous way and several nodes form a compact area as a cluster. this compact zone is shown as a cluster including six proteins in figure 2. it seems that these six proteins (including four varieties of fibrinogen, talin-1 (tln1), and thrombospondin-1 (thbs1)) play a critical role among the 35 queried deps in response to the covid-19 infection. investigation indicates that regulation of talin-1 effects platelet activation (21). the role of thrombospondin-1 in stimulating platelet aggregation is reported by jeff s. isenberg et al. (22). the biological terms that are connected to the deps are shown in figure 3 and table 1. to find the terms that are connected to the six critical deps, the terms that were related to at least one node of these critical proteins were determined. findings indicate that among the 31 terms in cluster 4, there are 29 terms (about 94%) that are linked to the several members of the six deps. all terms of cluster 2 are linked to the members of the critical deps, while the single term of cluster 1 has no connection to the critical set of deps. four terms (80%) of cluster 3 members have no connection to the mentioned deps. based on the analysis, it can be concluded that, clusters 2 and 4 (“platelet degranulation” and “hereditary factor i deficiency disease”, respectively) are the prominent terms that are dysregulated in response to covid-19 infection. hereditary factor i deficiency disease or fibrinogen deficiency is a blood disorder that is accompanied with decreased level of fibrinogen (afibrinogenemia, hypofibrinogenemia) or disturbed quality of fibrinogen (dysfibrinogenethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e27 mia) in circulation (23). as previously known, fibrinogen has a noticeable role in normal haemostasis in human body. it is the key element of promotion of fibrinolysis, clot formation, and platelet aggregation processes (24). as depicted in figure 4, about 76% of the determined biological terms are related to the “hereditary factor i deficiency disease”. the second cluster of terms is “platelet degranulation” class of pathway, which includes 3 terms. participation in haemostasis is the well-known role of platelet in blood. an essential process in response to vascular damage is platelet adhesion, which leads to initiation of thrombus creation at the time of hemorrhage and promotes wound healing (25, 26). there is a similar function that the two biological terms (“hereditary factor i deficiency disease” and “platelet degranulation”) are involved in: haemostasis. it can be concluded that disturbed haemostasis is the main dysfunction in severe cases of covid-19. what is more, clinical features of infection with coronavirus (1, 27) support the findings of our study. since covid-19 is a new disease, more data and sufficient patients are required to analyze the molecular events related to the promotion of infection. complementary investigations regarding different parameters such as age, geography, race, and other conditions are recommended to achieve a better understanding of the molecular mechanism of covid-19. 5. conclusion it can be concluded that platelet damage and disturbed haemostasis could be the main targets in severe cases of coronavirus infection. it is vital to follow patients’ condition by examining the introduced critical deps. 6. declarations 6.1. conflict of interest there is no conflict of interest. 6.2. acknowledgment this project was supported by shahid beheshti university of medical sciences. 6.3. authors’ contributions project was designed by mostafa rezaei tavirani and mona zamanian azodi. all authors had equal roles in the other actions. 6.4. funding and supports this project was supported by shahid beheshti university of medical sciences. references 1. marietta m, ageno w, artoni a, de candia e, gresele p, marchetti m, et al. covid-19 and haemostasis: a position paper from italian society on thrombosis and haemostasis (siset). blood transfusion. 2020;18(3):167. 2. madsbad s. covid-19 infection in people with diabetes. endocrinology. 2020;2020:1. 3. wang y, duan z, ma z, mao y, li x, wilson a, et al. epidemiology of mental health problems among patients with cancer during covid-19 pandemic. translational psychiatry. 2020;10(1):1-10. 4. cazzola m, skoda rc. translational pathophysiology: a novel 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reveals classifiers of covid-19 infection. cell systems. 2020;11(1):11-24. e4. 20. whetton ad, preston gw, abubeker s, geifman n. proteomics and informatics for understanding phases and identifying biomarkers in covid-19 disease. journal of proteome research. 2020;19(11):4219-32. 21. zhang d, qiao w, zhao y, fang h, xu d, xia q. curdione attenuates thrombin-induced human platelet activation: β1-tubulin as a potential therapeutic target. fitoterapia. 2017;116:106-15. 22. isenberg js, romeo mj, yu c, yu ck, nghiem k, monsale j, et al. thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cgmp signaling. blood, the journal of the american society of hematology. 2008;111(2):613-23. 23. peyvandi f. epidemiology and treatment of congenital fibrinogen deficiency. thrombosis research. 2012;130:s7-s11. 24. bornikova l, peyvandi f, allen g, bernstein j, mancojohnson m. fibrinogen replacement therapy for congenital fibrinogen deficiency. journal of thrombosis and haemostasis. 2011;9(9):1687-704. 25. ruggeri zm, mendolicchio gl. adhesion mechanisms in platelet function. circulation research. 2007;100(12):1673-85. 26. marcus aj. platelet function. new england journal of medicine. 1969;280(22):1213-20. 27. white d, macdonald s, edwards t, bridgeman c, hayman m, sharp m, et al. evaluation of covid-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays. international journal of laboratory hematology. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e27 table 1: list of 38 biological terms related to the queried differentially expressed proteins (deps) go term n ags % associated genes found translocation of slc2a4 (glut4) to the plasma membrane 1 4.17 [actb, ywhae, ywhaz] platelet degranulation 2 9.30 [apoh, cfl1, fga, fgb, fgg, orm1, orm2, pf4, ppbp, tagln2, thbs1, tln1] platelet activation, signaling and aggregation 2 4.94 [apoh, cfl1, fga, fgb, fgg, orm1, orm2, pf4, ppbp, tagln2, thbs1, tln1, ywhaz] response to elevated platelet cytosolic ca2+ 2 8.96 [apoh, cfl1, fga, fgb, fgg, orm1, orm2, pf4, ppbp, tagln2, thbs1, tln1] hemolytic-uremic syndrome 3 33.33 [cfhr1, cfhr3, cfi] atypical hemolytic uremic syndrome 3 33.33 [cfhr1, cfhr3, cfi] complement and coagulation cascades 3 7.06 [cfhr1, cfhr3, cfi, fga, fgb, fgg] complement cascade 3 8.62 [cfhr1, cfhr3, cfi, cfp, crp] regulation of complement cascade 3 8.51 [cfhr1, cfhr3, cfi, cfp] hemolytic-uremic syndrome 4 33.33 [cfhr1, cfhr3, cfi] hereditary factor i deficiency disease 4 100.00 [cfi, fga, fgb, fgg] dysfibrinogenemia, congenital 4 100.00 [fga, fgb, fgg] afibrinogenemia, congenital 4 100.00 [fga, fgb, fgg] atypical hemolytic uremic syndrome 4 33.33 [cfhr1, cfhr3, cfi] complement and coagulation cascades 4 7.06 [cfhr1, cfhr3, cfi, fga, fgb, fgg] platelet activation 4 4.03 [actb, fga, fgb, fgg, tln1] common pathway of fibrin clot formation 4 18.18 [fga, fgb, fgg, pf4] formation of fibrin clot (clotting cascade) 4 10.26 [fga, fgb, fgg, pf4] integrin cell surface interactions 4 4.71 [fga, fgb, fgg, thbs1] integrin signaling 4 14.81 [fga, fgb, fgg, tln1] grb2:sos provides linkage to mapk signaling for integrins 4 26.67 [fga, fgb, fgg, tln1] p130cas linkage to mapk signaling for integrins 4 26.67 [fga, fgb, fgg, tln1] map2k and mapk activation 4 12.50 [actb, fga, fgb, fgg, tln1] regulation of tlr by endogenous ligand 4 21.05 [fga, fgb, fgg, s100a8] signaling by moderate kinase activity braf mutants 4 10.64 [actb, fga, fgb, fgg, tln1] signaling by high-kinase activity braf mutants 4 13.89 [actb, fga, fgb, fgg, tln1] signaling by ras mutants 4 10.64 [actb, fga, fgb, fgg, tln1] signaling by braf and raf fusions 4 7.46 [actb, fga, fgb, fgg, tln1] paradoxical activation of raf signaling by kinase inactive braf 4 10.64 [actb, fga, fgb, fgg, tln1] oncogenic mapk signaling 4 6.76 [actb, fga, fgb, fgg, tln1] platelet aggregation (plug formation) 4 10.26 [fga, fgb, fgg, tln1] signaling downstream of ras mutants 4 10.64 [actb, fga, fgb, fgg, tln1] regulation of complement cascade 4 8.51 [cfhr1, cfhr3, cfi, cfp] selenium micronutrient network 4 5.43 [crp, fga, fgb, fgg, saa2] folate metabolism 4 6.85 [crp, fga, fgb, fgg, saa2] blood clotting cascade 4 13.04 [fga, fgb, fgg] human complement system 4 7.07 [cfi, cfp, crp, fga, fgb, fgg, thbs1] fibrin complement receptor 3 signaling pathway 4 7.14 [fga, fgb, fgg] the terms are extracted from ontology source; reactome_pathways_08.05.2020, clinvar_human-diseases_08.05.2020, kegg_08.05.2020, wikipathways_08.05.2020. term p value, term p value corrected with bonferroni step down, group p value, and term p value corrected with bonferroni step down ≤ 0.01 were considered. go: gene ontology; n: number of group; ags: associated genes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. zamanian-azodi et al. 6 figure 1: the queried 35 differentially expressed proteins (deps) are included in a network using string database and cytoscape software. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e27 figure 2: the action map for the 35 queried differentially expressed proteins (deps) via cluepedia. the blue and red colors of edges refer to binding and inhibition actions. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. zamanian-azodi et al. 8 figure 3: gene ontology results related to the 35 queried differentially expressed proteins (deps). the 38 terms are classified in the four groups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e27 figure 4: frequency of four classes of biological terms as a pie chart. different colors indicate designated groups of terms. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e22 or i g i n a l re s e a rc h the accuracy of emergency physicians in ultrasonographic screening of acute appendicitis; a cross sectional study ebrahim karimi1, mohammad aminianfar2, keivan zarafshani1, arash safaie3∗ 1. emergency department, be’sat hospital, aja university of medical sciences, tehran, iran. 2. department of infectious and tropical diseases, be’sat hospital, aja university of medical sciences, tehran, iran. 3. emergency department, sina hospital, tehran university of medical sciences, tehran, iran. received: june 2016; accepted: august 2016; published online: 10 january 2017 abstract: introduction: diagnostic values reported for ultrasonographic screening of acute appendicitis vary widely and are dependent on the operator’s skill, patient’s gender, weight, etc. the present study aimed to evaluate the effect of operator skill on the diagnostic accuracy of ultrasonography in detection of appendicitis by comparing the results of ultrasonography done by radiologists and emergency physicians. methods: this prospective diagnostic accuracy was carried out on patients suspected to acute appendicitis presenting to eds of 2 hospitals. after the initial clinical examinations, all the patients underwent ultrasonography for appendicitis by emergency physician and radiologist, respectively. the final diagnosis of appendicitis was based on either pathology report or 48-hour follow-up. screening performance characteristics of appendix ultrasonography by emergency physician and radiologist were compared using stata 11.0 software. results: 108 patients with the mean age of 23.91 ± 7.46 years were studied (61.1% male). appendicitis was confirmed for 37 (34.26%) cases. cohen’s kappa coefficient between ultrasonography by the radiologist and emergency physician in diagnosis of acute appendicitis was 0.51 (95% ci: 0.35 – 0.76). area under the roc curve of ultrasonography in appendicitis diagnosis was 0.78 (95% ci: 0.69 – 0.86) for emergency physician and 0.88 (95% ci: 0.81 – 0.94) for radiologist (p = 0.052). sensitivity and specificity of ultrasonography by radiologist and emergency physician in appendicitis diagnosis were 83.87% (95% ci: 67.32 – 93.23), 91.5% (95% ci: 81.89 – 96.52), 72.97% (95% ci: 55.61 – 85.63), and 83.10% (95% ci: 71.94 – 90.59), respectively. conclusion: findings of the present study showed that the diagnostic accuracy of ultrasonography carried out by radiologist (89%) is a little better compared to that of emergency physician (80%) in diagnosis of appendicitis, but none are excellent. keywords: appendicitis; ultrasonography; decision support techniques; emergency service, hospital; diagnosis © copyright (2017) shahid beheshti university of medical sciences cite this article as: karimi e, aminianfar m, zarafshani k, safaie a. the accuracy of emergency physicians in ultrasonographic screening of acute appendicitis; a cross sectional study. emergency. 2017; 5 (1): e22. 1. introduction appendicitis is a common surgical emergency in young adult males presenting to emergency department (ed) following abdominal pain (1, 2). diagnosis of appendicitis is a challenge for the medical team, as most of the time its classic signs and symptoms, such as pain, are not present and ∗corresponding author: corresponding author: arash safaie; departmnet of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. tel: +989111366966 e-mail: dr.safaie@yahoo.com laboratory tests do not have enough predictive value in this regard (3). meanwhile, rapid diagnosis and timely treatment can improve these patients’ management and reduce their hospital stay (4). laparotomy is the gold standard tool in diagnosis and treatment of appendicitis, but is invasive and has its own limitations and dangers. this has led the researchers to evaluate the diagnostic accuracy of other diagnostic tools such as computed tomography (ct) scan, magnetic resonance imaging (mri), and ultrasonography in detection of appendicitis. using each of these tests has its own advantages and limitations and the diagnostic values reported for them varies between different studies (5, 6). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. karimi et al. 2 this might be the reason that unnecessary laparotomies still have a high prevalence in abdominal pains suspected to be appendicitis (3). currently, bedside ultrasonography is deemed one of the most valuable screening tests in ed (7-11). this rapid diagnostic method can provide valuable results for the medical team in a short time with minimum cost (12). however, using ultrasonography for this purpose is still under debate. diagnostic values reported for ultrasonography vary widely and are dependent on the operator’s skill, patient’s gender, weight, etc. (13). yet, there is still no correct understanding of the mentioned factors on the diagnostic accuracy of ultrasonography. therefore, the present study was done aiming to evaluate the effect of operator skill on the diagnostic accuracy of ultrasonography in detection of appendicitis by comparing the results of ultrasonography done by radiologists and emergency physicians. 2. methods 2.1. study design this prospective diagnostic accuracy was carried out on patients suspected to acute appendicitis presenting to eds of be’sat and sina hospitals, tehran, iran, during 2014 and 2015 with the aim of comparing the ultrasonographic screening results of patients by emergency physicians and radiologists. protocol of the present study was approved by the ethics committee of aja university of medical sciences. before inclusion in the study, written informed consent for participation was obtained from all the patients or their relatives. the researchers adhered to the principles of the declaration of helsinki throughout the study. 2.2. participants samples were chosen by probability convenience method. patients with pain in the right lower quadrant of the abdomen suspected with acute appendicitis, who visited eds of the 2 hospitals were included. exclusion criteria consisted of acute abdomen in need of emergency laparotomy, confirmed diagnosis other than appendicitis (like ureteral stone), not undergoing ultrasonography by radiologist, emergency physician not being blinded to the result of the ultrasonography by radiologist, unavailability of laparotomy data or not being able to follow the patient, and discharge against medical advice. 2.3. procedure after the initial clinical examinations, all the patients underwent ultrasonography for appendicitis by emergency physician and radiologist, respectively. the final diagnosis of appendicitis was based on pathology report (in patients undergoing surgery) or 48-hour follow-up (reference test). ultrasonography was done using an ultrasonography machine (hs2000, honda, korea) with a linear probe and 5 – 7.5 mhz frequency. ultrasonographic diagnosis of acute appendicitis (figure 1) was based on > 6mm outer diameter of the appendix, not being compressible, presence of appendicolitis, loss of bowel movements, and free fluid accumulation around the appendix (14, 15). the site of probe placement in the right lower quadrant was where the most tenderness was found in the clinical examination and to reduce bowel gases and the distance of the probe to appendix, a gentle continuous pressure was applied to the site before carrying out ultrasonography. figure 2 shows the method of doing ultrasonography in patients. then the patients were followed. if the patient was sent to the operation room, their pathology result was counted as the confirmed diagnosis of presence or absence of appendicitis. however, the final diagnosis of patients who did not undergo laparotomy and were only followed for at least 48 hours was determined based on their follow-up and with the help of other diagnostic tests such as ct scan. the diagnostic and treatment process of the patients was done without considering ultrasonography results. in addition, in patients who were discharged from ed, 48 hours after discharge, follow-up was done on the phone to evaluate the persistence or improvement of the symptoms and those who still had pain were invited to ed for further evaluation. these cases were followed and their final diagnosis was done based on laparotomy or further 48 hour follow up. 2.4. statistical analysis minimum sample size needed for the present study was calculated to be 106 patients by considering 98.5% specificity of ultrasonography, 39.4% prevalence of appendicitis (12), α = 0.05 and d = 0.05. data analysis was done using stata 11.0 software. area under the receiver operating characteristic (roc) curve, sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and finally, brier score of the emergency physician and radiologist for acute appendicitis diagnosis were compared. to evaluate the agreement between the results of the radiologist and emergency physician, cohen’s kappa coefficient was calculated. presence of difference between the results of the emergency physician and radiologist was assessed using mcnemar’s chi square test. diagnostic value of the test was considered excellent if between 90-100%, good if 80 90%, fair if 70 – 80%, poor if 60 – 70%, and fail if 50 – 60%. significance level was considered p < 0.05. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e22 figure 1: sonographic views of appendix. figure 2: location of probe for appendix ultrasonography. 3. results: 108 patients with the mean age of 23.91 ± 7.46 years were studied (61.1% male). finally, based on the reference test appendicitis was confirmed for 37 (34.26%) cases. using ultrasonography, emergency physician and radiologist were able to diagnose 27 and 31 cases out of the 37, respectively. cohen’s kappa coefficient between ultrasonography by the radiologist and emergency physician in diagnosis of acute appendicitis was 0.51 (95% confidence interval (ci): 0.35 – 0.76). area under the roc curve of ultrasonography in appendicitis diagnosis was 0.78 (95% ci: 0.69 – 0.86) for emergency physician and 0.88 (95% ci: 0.81 – 0.94) for radiologist (figure 1). although it seems that area under the curve for radiologist is higher than emergency physician, the difference is only borderline (p = 0.052). area under the roc curve of ultrasonography performed by radiologist in men (auc = 0.86; 95% ci: 0.77 – 0.95) and women (auc = 0.89; 95% ci: 0.77 – 1.0) was not different (p = 0.68). these rates were (auc = 0.79; 95% ci: 0.69 – 0.89) for men and (auc = 0.77; 95% ci: 0.61 – 0.92) for women in ultrasonography performed by emergency physician, which did not show a difference (p = 0.80) (figure 2). diagnostic value of ultrasonography by radiologist and emergency physician are reported in table 1. sensitivity and specificity of ultrasonography by radiologist in appendicitis diagnosis were 83.87% and 91.5%, respectively. these values for emergency physician were 72.97% and 83.10%, respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. karimi et al. 4 table 1: screening performance characteristics of ultrasonography performed by radiologist and emergency physician in detection of acute appendicitis value radiologist emergency physician true positive 31 27 true negative 65 59 false positive 6 12 false negative 6 10 sensitivity 83.78 (67.32-93.23) 72.97 (55.61-85.63) specificity 91.5 (81.89-96.52) 83.10 (71.94-90.59) positive predictive value 83.78 (67.32-93.23) 69.23 (52.27-82.45) negative predictive value 91.55 (81.89-96.52) 85.51 (74.49-92.46) positive likelihood ratio 9.91 (4.55-21-60) 4.32 (2.49-7-50) negative likelihood ratio 0.18 (0.08-0.37) 0.32 (0.19-0.56) accuracy 88.89 (82.96-94.48) 79.63 (72.03-87.23) figure 3: comparison of area under the receiver operating characteristic (roc) curve for ultrasonography carried out by radiologist and emergency physician.âăč the accuracies calculated were about 89% and 80%, respectively. brier score of the ultrasonography performed by radiologist was 0.11 and its scaled reliability was 0.01. these values were 0.20 and 0.05 for ultrasonography performed by emergency physician. these findings indicate the good predictive accuracy and reliability for both specialists in diagnosis of acute appendicitis using ultrasonography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e22 figure 4: comparing area under the receiver operating characteristic (roc) curve of ultrasonography carried out by radiologist and emergency physician for diagnosing acute appendicitis based on patients’ gender. 4. discussion: findings of the present study showed that although diagnostic value of ultrasonography by radiologist is a little better than that of emergency physician, none are excellent. reported diagnostic value of ultrasonography in appendicitis diagnosis varies between studies (16, 17). the results of a meta-analysis showed that sensitivity and specificity of ultrasonography in appendicitis diagnosis are 86% and 81%, respectively. positive and negative predictive values reported in the study were 84% (46-95%) and 85% (60 – 97%), respectively. the researchers of the meta-analysis believe that a variety of factors are responsible for the difference between studies. the most important reported factor was the dependence of ultrasonography on operator’s skill (18). although the findings of the present study confirms this hypothesis to some extent, the diagnostic value of ultrasonography by radiologist was not significantly different from that of emergency physician and the difference was on the borderline. in addition to the dependence of ultrasonography on the operator’s skill, some studies believed that the diagnostic value of ultrasonography is also dependent on the patient’s gender. these studies express that due to anatomic differences, differentiation of acute abdominal pains is very difficult in women of childbearing age (19-21). for this purpose, in the present study the diagnostic value of ultrasonography was evaluated based on patients’ gender. however, the findings showed that the diagnostic value of ultrasonography for appendicitis diagnosis does not vary between women and men. some studies have attempted to increase the sensitivity of ultrasonography by adding other diagnostic tests. for example aspelund et al. added mri and showed that in children suspected to appendicitis, a radiation-free diagnostic protocol screening the suspected cases, using ultrasonography and mri, was a simple method and had a value equal to ct scan (22). in contrast, other studies have questioned the combined strategy for diagnosis of appendicitis. in a study, leeuwenburgh et al. showed that although screening based on ultrasonography and ct scan for suspected patients has equal value to mri, both methods classify about half of those with ruptured appendicitis as healthy. these researchers concluded that triage of appendicitis based on imaging is not appropriate for conservative treatment and may cause huge mistakes in patient management (23) since false positive results could lead to an increase in unnecessary appendectomy, while false negative results might cause a delay in treatment and therefore, worsening of the patient’s condition. to solve this problem, the researchers suggest to not solely rely on imaging evaluations for diagnosis of appendicitis. rather, use a mixture of diagnostic techniques including history taking and clinical examination, scoring systems, inflammatory biomarkers, in addition to imaging studies (18, 24). 5. limitations: among the limitations of the present study is its observational nature .therefore, eliminating all the confounding factors and probable biases from the study was not possible. among these items are convenience sampling that makes selection bias probable. in addition, the present study is a 2centered one and this makes generalizability of the data to all clinical conditions a bit hard. finally, not evaluating weight this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. karimi et al. 6 and body mass index (bmi), which can affect the findings, is another limitation of this study. 6. conclusion: findings of the present study showed that the diagnostic accuracy of ultrasonography carried out by radiologist (89%) is a little better compared to that of emergency physician (80%) in diagnosis of appendicitis, but none are excellent. 7. appendix 7.1. acknowledgements the authors wish to thank all emergency department staff of sina and be’sat hospitals for their contribution. this article is extracted from the residency thesis of keivan zarafshan. 7.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. conflict of interest none. 7.4. funding none. references 1. humes d, simpson j. acute appendicitis. bmj. 2006;333(7567):530-4. 2. buckius mt, mcgrath b, monk j, grim r, bell t, ahuja v. changing epidemiology of acute appendicitis in the united states: study period 1993–2008. journal of surgical research. 2012;175(2):185-90. 3. kollar d, mccartan d, bourke m, cross k, dowdall j. predicting acute appendicitis a comparison of the alvarado score, the appendicitis inflammatory response score and clinical assessment. world journal of surgery. 2015;39(1):104-9. 4. bower rj, bell mj, ternberg jl. controversial aspects of appendicitis management in children. archives of surgery. 1981;116(7):885-7. 5. livingston eh, woodward wa, sarosi ga, haley rw. disconnect between incidence of nonperforated and perforated appendicitis: implications for pathophysiology and management. annals of surgery. 2007;245(6):886-92. 6. andersson m, kolodziej b, andersson r. structured management of patients with suspected acute appendicitis using a clinical score and selective imaging (strappscore). 2015. 7. yousefifard m, baikpour m, ghelichkhani p, asady h, nia ks, jafari am, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. emergency. 2016;4(1):1. 8. yousefifard m, baikpour m, ghelichkhani p, asady h, darafarin a, esfahani mra, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. emergency. 2016;4(2):55. 9. rahimi-movaghar v, yousefifard m, ghelichkhani p, baikpour m, tafakhori a, asady h, et al. application of ultrasonography and radiography in detection of hemothorax: a systematic review and meta-analysis. emergency-an academic emergency medicine journal. 2016;4(3):116-26. 10. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, ghanbari mjh, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. emergency. 2015;3(4):127. 11. ebrahimi a, yousefifard m, kazemi hm, rasouli hr, asady h, jafari am, et al. diagnostic accuracy of chest ultrasonography versus chest radiography for identification of pneumothorax: a systematic review and metaanalysis. tanaffos. 2014;13(4):29-40. 12. mallin m, craven p, ockerse p, steenblik j, forbes b, boehm k, et al. diagnosis of appendicitis by bedside ultrasound in the ed. the american journal of emergency medicine. 2015;33(3):430-2. 13. kaewlai r, lertlumsakulsub w, srichareon p. body mass index, pain score and alvarado score are useful predictors of appendix visualization at ultrasound in adults. ultrasound in medicine & biology. 2015;41(6):1605-11. 14. pickuth d, heywang-kobrunner sh, spielmann rp. suspected acute appendicitis: is ultrasonography or computed tomography the preferred imaging technique? european journal of surgery. 2000;166(4):315-9. 15. paulson ek, kalady mf, pappas tn. suspected appendicitis. new england journal of medicine. 2003;348(3):236-42. 16. elikashvili i, tay et, tsung jw. the effect of point-of-care ultrasonography on emergency department length of stay and computed tomography utilization in children with suspected appendicitis efecto de la ecografia en el punto de atencion en la duracion de la estancia en el servicio de urgencias y en la utilizacion de la tomografia computarizada en los ninos con sospecha de apendicitis. academic emergency medicine. 2014;21(2):163-70. 17. pinto f, pinto a, russo a, coppolino f, bracale r, fonio p, et al. accuracy of ultrasonography in the diagnosis of acute appendicitis in adult patients: review of the literathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e22 ture. critical ultrasound journal. 2013;5(1):1-3. 18. yu s-h, kim c-b, park jw, kim ms, radosevich dm. ultrasonography in the diagnosis of appendicitis: evaluation by meta-analysis. korean journal of radiology. 2005;6(4):267-77. 19. angelelli g, moschetta m, sabato l, morella m, scardapane a, ianora aas. value of “protruding lips” sign in malignant bowel obstructions. european journal of radiology. 2011;80(3):681-5. 20. lorusso f, fonio p, scardapane a, giganti m, rubini g, ferrante a, et al. gatrointestinal imaging with multidetector ct and mri. recenti progressi in medicina. 2012;103(11):493. 21. bendeck se, nino-murcia m, berry gj, jeffrey jr rb. imaging for suspected appendicitis: negative appendectomy and perforation rates 1. radiology. 2002;225(1):131-6. 22. aspelund g, fingeret a, gross e, kessler d, keung c, thirumoorthi a, et al. ultrasonography/mri versus ct for diagnosing appendicitis. pediatrics. 2014;133(4):58693. 23. leeuwenburgh mmn, wiezer mj, wiarda bm, bouma wh, phoa ssks, stockmann hbac, et al. accuracy of mri compared with ultrasound imaging and selective use of ct to discriminate simple from perforated appendicitis. british journal of surgery. 2014;101(1):e147-e55. 24. nasiri s, mohebbi f, sodagari n, hedayat a. diagnostic values of ultrasound and the modified alvarado scoring system in acute appendicitis. international journal of emergency medicine. 2012;5(1):1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: limitations: conclusion: appendix references emergency. 2018; 6 (1): e57 or i g i n a l re s e a rc h low-dose fentanyl, propofol, midazolam, ketamine and lidocaine combination vs. regular dose propofol and fentanyl combination for deep sedation induction; a randomized clinical trial afshin amini1, ali arhami dolatabadi1, hamid kariman1, hamidreza hatamabadi1, elham memary2, sohrab salimi2, shahram shokrzadeh3∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. anesthesiology department, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shahid rajaee hospital, tonekabon, iran. received: august 2018; accepted: september 2018; published online: 2 october 2018 abstract: introduction: need for procedural sedation and analgesia (psa) is felt in emergency department (ed) more and more each day. this study aimed to compare the effectiveness of low-dose fentanyl, propofol, midazolam, ketamine and lidocaine combination with regular dose of propofol and fentanyl combination for induction of deep sedation. methods: in this single-blind clinical trial, candidate patients for sedation and analgesia aged more than 15 and less than 60 years old, with pain score ≥6 were allocated to one of the groups using block randomization and were compared regarding onset of action, recovery time, and probable side effects. results: 125 patients with the mean age of 37.8 ± 14.3 years were randomly allocated to each group. 100% of the patients in group 1 (5 drugs) and 56.5% of the patients in group 2 (2 drugs) were deeply sedated in the 3rd minute after injection. the 2 groups were significantly different regarding onset of action (p = 0.440), recovery time (p = 0.018), and treatment failure (p < 0.001). conclusion: low-dose fentanyl, propofol, midazolam, ketamine and lidocaine combination was more successful in induction of deep sedation compared to regular dose of propofol and fentanyl combination. recovery time was a little longer in this group and both groups were similar regarding drug side effects and effect on vital signs. keywords: clinical trial; deep sedation; emergency service, hospital; ketamine; propofol; analgesia © copyright (2018) shahid beheshti university of medical sciences cite this article as: amini a, arhami dolatabadi a, kariman h, hatamabadi h, memary e, salimi s, shokrzadeh sh. low-dose fentanyl, propofol, midazolam, ketamine and lidocaine combination vs. regular dose propofol and fentanyl combination for deep sedation induction; a randomized clinical trial. emergency. 2018; 6(1): e57. 1. introduction pain and excessive agitation are usually big obstacles for providing medical services (1, 2). therefore, need for procedural sedation and analgesia (psa) is felt in emergency department (ed) more and more each day. it is estimated that 10% of ed patients need some kind of sedative (3-5). psa is a technique used to induce a level of anesthesia and analgesia for pa∗corresponding author: shahram shokrzadeh; emergency department, shahid rajaee hospital, imam khomeini street, tonekabon, iran. tel: 00989111954119 email: shahram.shokrzadeh@gmail.com tients in order to undergo unpleasant and painful procedures without changes in cardiopulmonary function. drugs used for sedation induction can be classified in 2 general groups of sedatives such as propofol, ketamine, etomidate, and midazolam and analgesics such as fentanyl, remifentanil, morphine, and ketamine (6). these drugs have the potential for causing dangerous side effects such as respiratory, cardiac and vascular depression, especially in higher doses (7). finding new compounds that have few side effects in addition to effective and deep psa with rapid recovery of patients from psa is of great interest. numerous studies have evaluated and compared drug compounds. both propofol-ketamine and propofol-fentanyl have provided sufficient sedation and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. amini et al. 2 analgesia during dressing change for burn patients (8). both compounds have also provided sufficient analgesia for doing endoscopy of the upper digestive system but propofolketamine compound has led to more stable hemodynamics and deeper analgesia (9). using low-dose drugs can prevent manifestation of drug side effects. however, there is no accurate data regarding the effects of using low-dose sedative and analgesic drugs. therefore, this study aimed to compare the effectiveness and safety of using low-dose sedative and analgesic drugs (including propofol, ketamine, midazolam, fentanyl, and lidocaine) with regular dose of propofol and fentanyl in patients in need of psa presenting to ed. 2. methods 2.1. study design and setting the present study is a clinical trial carried out aiming to compare the effectiveness of low-dose 5 drug combination (fentanyl, propofol, midazolam, ketamine, and lidocaine) with regular dose of 2 drug combination (propofol-fentanyl) for induction of deep sedation in patients presenting to the ed of imam hossein teaching hospital, during 6 months in 2015. in line with the declaration of helsinki, the researchers adhered to ethical principles and kept patient data confidential. before entering the study, all participants were given explanations regarding the study protocol and then written informed consent was obtained from them. the protocol of the study was registered on the iranian registry of clinical trials under the number irct2015112525235n1 and was approved by the ethics committee of shahid beheshti university of medical sciences under the license number: sbmu.rec.13930717. 2.2. participants in this study, candidate patients for psa, according to the decision of a senior emergency medicine specialist, whose age was over 15 and under 60 years and had a pain score equal to or higher than 7 (based on numeric analog scale: nas) were included. in cases of patients not wanting to participate, previous allergy to drugs used in the study, allergy to protein products such as egg and soy, hemodynamic instability, increased intracranial pressure and lactating and pregnant women, they were excluded. 2.3. intervention in this study, patients were randomly allocated to 2 groups via block randomization. group 1 consisted of patients receiving a low-dose fentanyl (0.5 -1 µg/kg), propofol (0.5 mg/kg), midazolam (0.1–0.02 mg/kg), ketamine (0.2–0.25 mg/kg), and lidocaine (0.5 mg/kg) combination and group 2 included patients receiving regular dose of propofol (1 mg/kg) and fentanyl (1 mg/kg). drug injection was done during 20 30 seconds using syringes with a similar volume and color. all the patients were under close cardiac, respiratory, blood pressure, and blood o2 saturation monitoring during the procedure. time interval between receiving drug and deep psa induction was considered as the drug’s onset of action. in addition, the time interval between deep psa and complete recovery was considered as recovery time. for measuring pain severity, nas was used and for measuring depth of psa, ramsay system was applied. ramsey score of 6 was considered as deep psa and score of 2 was considered as recovery. pain score equal to or higher than 6 was considered severe pain. 2.4. data gathering to gather data, a checklist consisting of demographic data (age, sex, weight); vital signs (blood pressure, respiratory rate, heart rate, o2 saturation) before and during procedure; reason for requiring psa (upper/lower limb injury, soft tissue injury); and final studied outcome (onset of drug action, recovery time, probable side effects, and patient and physician’s satisfaction) was designed and used. data gathering was done by a senior emergency medicine resident in charge of carrying out the study. patients and data analyzer were blind to the administered drugs. 2.5. outcome onset of action and recovery time were considered as primary outcomes and drug side effects such as nausea and vomiting, apnea and hemodynamic instability in addition to patient and physician’s satisfaction were considered secondary outcomes. 2.6. statistical analysis considering 17 minutes standard deviation in recovery time, 5% error, 10% desired precision, and 90% power, the minimum sample size required for each group was estimated to be 61 cases (10). data were analyzed using spss 20. qualitative variables were reported as frequency and percentage, and quantitative ones as mean ± standard deviation. chi squared and fisher’s exact tests were applied for analytical comparisons. non-parametric test of chi-square for trend was used for evaluating the frequency of successful psa cases and assessing recovery time. significance level was considered to be p < 0.05. 3. results 3.1. baseline characteristics 125 patients with the mean age of 37.8 ± 14.3 (15-60) years were studied (75.2% male). 63 (50.4%) patients were randomly allocated to group 1 and 62 (49.6%) to group 2. table 1 compares the baseline characteristics of the studied patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e57 table 1: baseline characteristics of the studied patients variable group 1 (n = 63) group 2 (n = 62) p sex male 45 (71.4) 46 (74.2) 0.80 female 18 (28.6) 16 (25.8) age (year) mean ± standard deviation 37.2 ± 13.2 38.2 ± 15.6 0.70 weight (kg) mean ± standard deviation 73.4 ± 12.4 70.1 ± 11.1 0.12 history of psa* no 56 (91.8) 54 (87.1) 0.40 yes 5 (8.2) 8 (12.9) reason for requiring psa* upper limb injury 45 (71.4) 44 (71.0) lower limb injury 15 (23.8) 16 (25.8) 0.99 soft tissue injury 1 (1.6) 1 (1.6) other 2 (3.2) 1 (1.6) history of underlying illness yes 5 (8.2) 8 (12.9) 0.29 no 58 (92.1) 54 (87.1) vital signs heart rate (/minute) 84.5 ± 11.6 88.0 ± 11.2 0.09 respiratory rate (/minute) 15.6 ± 1.8 16.1 ± 1.9 0.23 systolic blood pressure (mmhg) 123.4 ± 12.0 124.8 ± 12.7 0.52 diastolic blood pressure (mmhg) 79.9 ± 9.4 79.3 ± 19.6 0.73 arterial o2 saturation (%) 97.3 ± 1.6 98.3 ± 13.3 0.63 psa: procedural sedation and analgesia; data are shown as mean ± standard deviation or frequency (%). figure 1: kaplan-meier curve of recovery time (in minutes) for the 2 studied groups. the 2 groups were not significantly different regarding demographic data. 3.2. comparison of outcomes table 2 compares the outcome of treatment in the 2 groups. the 2 groups were significantly different regarding onset of action (p = 0.440), recovery time (p = 0.018), treatment failure (p < 0.001), physician’s satisfaction (p < 0.001), and patient’s satisfaction (p < 0.001). kaplan-meier curve of recovery time for the 2 studied groups is shown in figure 1. 100% of the patients in group 1 and 56.5% of the patients in group 2 were deeply sedated in the 3rd minute after injection. in total, 5 cases of side effect due to psa were detected that included 3 (2.4%) vertigo and 2 (1.6%) vomiting cases. the cost of the treatment regimen for a 70-kg patient was 33750 rials (1.7 us dollar) in group 2 (2 drug combination) and 37400 rials (1.9 us dollar) in group 1 (5 drug combination). 4. discussion based on the findings of the present study, low-dose propofol, ketamine, midazolam, fentanyl, and lidocaine combination had a higher success rate in inducing deep sedation, and patient and physician’s satisfaction compared to fentanyl and propofol combination with regular dose. recovery time in this group was slightly longer and the 2 groups did not differ significantly regarding drug side effects and influence on vital signs. as mentioned before, finding new drugs that have few side effects in addition to effective and deep psa with rapid recovery is of great interest among physicians. in line with the current study, ebrahimi et al. aimed to compare propofol-midazolam and propofol-fentanyl regimens in patients undergoing microlaryngeal surgery and showed that mean arterial o2 saturation during laryngoscopy was further reduced in fentanyl group, while recovery time was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. amini et al. 4 table 2: comparison of treatment characteristics between low-dose multi-drug group (group 1) and propofol-fentanyl combination group (group 2) variable group 1 group 2 p onset of action (minute) mean ± standard deviation 1.73 ± 0.62 1.36 ± 1.29 0.044 treatment failure number (%) 0 (0) 22 (37.1) < 0.001 recovery time (minute) mean ± standard deviation 6.48 ± 1.84 5.02 ± 4.47 0.03 vital signs heart rate (/minute) 78.2 ± 8.8 83.1 ± 9.8 0.006 systolic blood pressure (mmhg) 119.0 ± 12.1 121.0 ± 11.6 0.36 diastolic blood pressure (mmhg) 74.8 ± 9.0 76.25 ± 9.7 0.73 arterial o2 saturation (%) 95.5 ± 3.1 91.9 ± 6.8 0.00003 side effects none 61 (96.8) 59 (95.2) vertigo 1 (1.6) 2 (3.2) 0.836 vomiting 1 (1.6) 1 (1.6) patient’s satisfaction dissatisfied 1 (1.6) 1 (1.6) partial 19 (30.2) 56 (90.3) < 0.001 complete 43 (68.3) 5 (8.1) physician’s satisfaction dissatisfied 1 (1.6) 1 (1.6) partial 19 (30.2) 53 (86.9) < 0.001 complete 43 (68.3) 7 (11.5) data are shown as mean ± standard deviation or frequency (%). shorter in midazolam group (11). comparison of propofolketamine and propofol-fentanyl compounds for psa induction in pediatric burn patients during change of dressing showed that there is no significant difference between these combinations regarding heart rate, systolic blood pressure, arterial o2 saturation, respiratory rate, and sedation score during psa (8). erden et al. showed that adding a low dose of ketamine to propofol-fentanyl combination leads to decreased risk of drop in arterial o2 saturation and less need for additional propofol for induction of analgesia (12). using propofol-ketamine combination results in more stable hemodynamics and deeper analgesia in psa induction for pediatrics during upper gastrointestinal tract endoscopy compared to propofol-fentanyl. however, it had more side effects (9). akin et al. also revealed that propofol-fentanyl and propofol-ketamine groups had no significant difference regarding analgesia during endometrial biopsy (13). as can be seen, most studies expressed that combination of propofol and ketamine or propofol and midazolam are better regimens for psa induction compared to propofol-fentanyl. other observations emphasize that ketamine is a safe drug and a proper sedative for use in eds (14). the advantage of the present study over other similar ones is using low doses of multiple sedatives for psa induction. most study protocols have been based on using 2 or at most 3 drugs, while this study designed a 5-drug protocol. confirmation of the results of the current study requires carrying out further studies with stronger methodologies and considering different racial characteristics. 5. limitation the study being single-blind is among the most important limitations of this study. 6. conclusion based on the findings of the present study, low-dose fentanyl, propofol, midazolam, ketamine and lidocaine combination was more successful in induction of deep sedation compared to regular dose of propofol and fentanyl combination and was associated with higher satisfaction among both patients and physicians. recovery time was a little longer in this group and the 2 groups were not significantly different regarding drug side effects and effect on vital signs. 7. appendix 7.1. acknowledgement the present article is derived from dr. shahram shokrzadeh’s thesis, numbered 105, to achieve his specialist degree in emergency medicine from shahid beheshti university of medical sciences. hereby, we sincerely thank all the staff of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e57 emergency department of imam hossein hospital for assisting us in all stages of the study. 7.2. authors’ contribution all the authors meet the 4 criteria for authorship based on recommendations of the international committee of medical journal editors. authors’ orcids ali arhami dolatabadi: 0000-0001-9492-9520 hamidreza hatamabadi: 0000-0002-9085-8806 elham memary: 0000-0002-4845-9342 sohrab salimi: 0000-0002-0331-1619 shahram shokrzadeh: 0000-0002-8170-7686 7.3. funding/support no financial support has been received for this project. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. karceski s, morrell m, carpenter d. the expert consensus guideline series: treatment of epilepsy. epilepsy & behavior. 2001;2(6):a1-a50. 2. group tc. rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. bmj: british medical journal. 2003;327(7417):708-14. 3. esmailian m, moshiri r, zamani m. comparison of the analgesic effect of intravenous acetaminophen and morphine sulfate in rib fracture; a randomized clinical trial. 2014. 2014;3(3):4. 4. faridaalaee g, rahmani sh, mehryar h, bina shishavan s, merghati sz, valizade hasanloei ma, et al. comparison of intravenous metoclopramide and acetaminophen in primary headaches: a randomized controlled trial. 2014. 2014;3(2):5. 5. alimohammadi h, shojaee m, samiei m, abyari s, vafaee a, mirkheshti a. nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial. 2013. 2013;1(1):4. 6. hoffman gm, nowakowski r, troshynski tj, berens rj, weisman sj. risk reduction in pediatric procedural sedation by application of an american academy of pediatrics/american society of anesthesiologists process model. pediatrics. 2002;109(2):236-43. 7. apfelbaum jl, silverstein jh, chung ff, connis rt, fillmore rb, hunt se, et al. practice guidelines for postanesthetic carean updated report by the american society of anesthesiologists task force on postanesthetic care. the journal of the american society of anesthesiologists. 2013;118(2):291-307. 8. tosun z, esmaoglu a, coruh a. propofol–ketamine vs propofol–fentanyl combinations for deep sedation and analgesia in pediatric patients undergoing burn dressing changesa. pediatric anesthesia. 2008;18(1):43-7. 9. tosun z, aksu r, guler g, esmaoglu a, akin a, aslan d, et al. propofol-ketamine vs propofol-fentanyl for sedation during pediatric upper gastrointestinal endoscopy. pediatric anesthesia. 2007;17(10):983-8. 10. correia lm, bonilha dq, gomes gf, brito jr, nakao fs, lenz l, et al. sedation during upper gi endoscopy in cirrhotic outpatients: a randomized, controlled trial comparing propofol and fentanyl with midazolam and fentanyl. gastrointestinal endoscopy. 2011;73(1):45-51. e1. 11. sajedi1 pay, ahmad%a bigi2, ali akbar%a rezaie3, mahin%a mehrabi kooshki4, ali. comparative evaluation of vital signs stability, sedation and analgesia scores with two methods of sedation: propofol+fentanyl and ketamine+fentanyl during perm cath insertion. research in medicine. 2010;34(1):13-9. 12. aydin erden i, gulsun pamuk a, akinci sb, koseoglu a, aypar u. comparison of propofol-fentanyl with propofol-fentanyl-ketamine combination in pediatric patients undergoing interventional radiology procedures. pediatric anesthesia. 2009;19(5):500-6. 13. akin a, guler g, esmaoglu a, bedirli n, boyaci a. a comparison of fentanyl-propofol with a ketamine-propofol combination for sedation during endometrial biopsy. journal of clinical anesthesia. 2005;17(3):187-90. 14. treston g, bell a, cardwell r, fincher g, chand d, cashion g. what is the nature of the emergence phenomenon when using intravenous or intramuscular ketamine for paediatric procedural sedation? emergency medicine australasia : ema. 2009;21(4):315-22. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e39 or i g i n a l re s e a rc h familiarity of physicians and nurses with different aspects of oxygen therapy; a brief report reza goharani1, mirmohammad miri1, mehran kouchek1, mohammad sistanizad2,3∗ 1. department of critical care, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of clinical pharmacy, faculty of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 3. department of pharmaceutical care unit, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: april 2016; accepted: august 2016; published online: 11 january 2017 abstract: introduction: oxygen is a drug and physician and nurses should be familiar with the effects and potential risks of oxygen therapy. the current study aimed to assess familiarity of physicians and nurses with various aspects of oxygen therapy. methods: in this cross sectional study, the familiarity of physicians and nurses with various aspects of oxygen therapy in a teaching hospital was evaluated using a validated questionnaire. the collected data were analyzed using spss 21 software. results: 57 physicians and 79 nurses returned the completed questionnaire (response rate 97.1%). mean clinical work experience of participants was 6.9±5.7 (1–15) years. 98.2% of physicians believed that oxygen therapy can be associated with risk and should be recorded in the patient’s medical file. these measures were 92.4% and 98.2% for nurses. 38 (27.9%) participants correctly pointed out the reasons for oxygen therapy. regarding necessary measurements and monitoring for oxygen therapy, 49 (86%) physicians and 65 (82.3%) nurses chose the correct answer. in addition, regarding necessity of blood gas analysis during oxygen therapy, 44 (77.2%) physicians and 55 (69.6%) nurses chose the correct answer. conclusion: the findings showed that the familiarity level of participants with some aspects of o2 therapy such as its indications, necessary measurements and monitoring during therapy, and identifying delivery devices was fair to weak (<80%). keywords: oxygen; oxygen inhalation therapy; knowledge; adverse effects; physicians; nurses © copyright (2017) shahid beheshti university of medical sciences cite this article as: goharani r, miri m, kouchek m, sistanizad m. familiarity of physicians and nurses with different aspects of oxygen therapy; a brief report. emergency. 2017; 5 (1): e39. 1. introduction oxygen is one of the most common drugs used in secondary care in hospital. oxygen is an essential component of resuscitation, acute medical care, basic life support, anesthesia and postoperative care. when oxygen is used appropriately, it can save lives. on the other hand, any errors in oxygen therapy can worsen a patient’s condition and can even be life-threatening (1). nowadays, the benefits and potential complications of oxygen therapy are well known; however, oxygen therapy is often done without special attention and sufficient knowledge (2-5). there are several guidelines ∗corresponding author: mohammad sistanizad; department of pharmaceutical care unit, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 0098-9122784895, fax: 0098-2188200087 , email: sistanizadm@sbmu.ac.ir and protocols for appropriate oxygen therapy (2, 6). it has been shown that use of protocols for oxygen therapy in hospital wards can be very helpful in reducing errors during this process (7-9). previous studies have evaluated the use of oxygen in hospitals (10, 11). these studies reveal that doctors often prescribe oxygen improperly and without adequate supervision. modified charts for prescribing oxygen and related requirements have been proposed (2, 11). dodd et al. have shown that introduction of a specific prescription chart for oxygen improves the quality of its prescription by junior doctors from 55% to 91%. however, these recommendations had a positive effect on patient care only if health professionals had proper information and sufficient understanding of oxygen therapy and its correct administration (12). to ensure the safe and effective oxygen delivery, flow rate, dose, devices, time, and method of monitoring should be given special attention and doctors and nurses should be familiar with the effects and potential risks of oxygen therapy. based on the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. goharani et al. 2 above-mentioned, this study aimed to assess familiarity of physicians and nurses with various aspects of oxygen therapy. 2. methods 2.1. study design this cross sectional study was conducted in a teaching hospital affiliated to shahid beheshti university of medical sciences, tehran, iran, in 2014. the familiarity of physicians and nurses with various aspects of oxygen therapy was evaluated using a predesigned questionnaire. after a full explanation about the study design, written informed consent was obtained from all nurses and physicians. all information about the participants was kept confidential. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences. 2.2. participants 60 physicians and 80 nurses working in different hospital wards were enrolled. all participants had some experiences in oxygen therapy. it was assumed that all participants had the basic skills and training about oxygen therapy. questionnaires were anonymous and 20 minutes were given to each participant to complete the questionnaire without conferring. 2.3. questionnaire internet search for international and local oxygen delivery guidelines was done and the most common and appropriate ones were used for designing a questionnaire (13, 14). two consultant respiratory physicians, independently evaluated and confirmed the questionnaire items and responses. it was expected that questions about parameters in oxygen therapy would assess topics that all doctors and nurses had undergone in education and training courses. in the first part of the questionnaire, participants were asked to identify oxygen delivery devices and choose their correct names. then in the second part, a variety of questions about how to prescribe and deliver oxygen, and reasons for oxygen prescription were asked. the familiarity rate was categorized into five groups based on likert scale: ≥ 90% as excellent, 80-90% good, 7080% fair, 60-70% weak and < 60% poor. 2.4. statistical analysis data from the completed questionnaires were extracted and analyzed using spss version 17. to describe the data, frequency, percentage, mean, standard deviation, median, and interquartile range (iqr) were used. 3. results: 3.1. baseline characteristics 60 physicians and 80 nurses were studied. the response rate was 97.1%, and a total of 136 participants [57 physicians (54.4% female) and 79 nurses (70.9% female)] were involved. average work experience of participants was 6.9 ± 5.7 years (1-15). 70 (51.5%) participants stated that there was a protocol to prescribe oxygen in their ward. the usual method of oxygen delivery in hospital wards were nasal cannula (58.1%) and simple mask (33.1%), respectively. table 1 shows the usage percentage of different o2 delivery devices in the studied hospital. 3.2. knowledge 98.2% of physicians believed that oxygen therapy can be associated with risk and should be recorded in the patient’s medical file. these measures were 92.4% and 98.2% for nurses. table 2 shows the familiarity percentage of participants with different oxygen delivery devices. 38 (27.9%) participants correctly pointed out the reasons for oxygen therapy. regarding necessary measurements and monitoring for oxygen therapy, 49 (86%) physicians and 65 (82.3%) nurses chose the correct answer. in addition, regarding necessity of blood gas analysis during oxygen therapy, 44 (77.2%) physicians and 55 (69.6%) nurses chose the correct answer. 4. discussion: the findings showed that the familiarity level of participants with some aspects of o2 therapy such as its indications, necessary measurements and monitoring during therapy, and identifying delivery devices was fair to weak (<80%). previous studies had evaluated the use of oxygen at hospitals in other countries (10, 11). in a study conducted in 2006 by ganeshan et al., knowledge of 53 nurses and 40 doctors that worked in intensive care unit of the general hospital in uk and were active in oxygen prescription, was evaluated. 25% of the physicians and 50% of the nurses could not prescribe the right dose and method of oxygen therapy in cardiorespiratory arrest cases. they concluded that doctors and nurses did not have sufficient knowledge and understanding of oxygen therapy (9). in a similar study, brokalaki et al. assessed the knowledge of oxygen therapy in seven hospitals in a major city of greece, in 2004. the questionnaire was completed by 105 head-nurses. the results showed that training programs, protocols and guidelines should be mandatory to ensure proper use of oxygen therapy by nursing personnel (14). in our study, approximately half of participants said that there is no protocol to prescribe oxygen this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e39 table 1: the most often used oxygen delivery devices in imam hossein hospital devices number (%) nasal cannula 79 (58.1) simple face mask 45 (33.1) non-rebreathing face mask with reservoir bag 6 (4.4) venturi mask 6 (4.4) table 2: familiarity of participants with different oxygen delivery devices devices nurses doctors nasal specs/prongs/cannula 79 (100) 54 (94.7) bag mask ventilation 78 (98.7) 57 (100) venturi mask 76 (96.2) 50 (87.7) rebreathing face mask 41 (51.9) 40 (70.2) non-rebreathing face mask with reservoir bag 41 (51.9) 45 (78.9) data were presented as number and percentage. in their wards, despite the existence of several international guidelines for proper oxygen therapy (2, 6). however, only 51.9 to 78.9% of the nurses and doctors recognized o2 delivery devices such as non-rebreathing mask with reservoir bag, which is consistent with ganeshan et al. results (13). in the present study, only 38 participants (27.9%) correctly pointed out the indications for oxygen therapy, namely decreased level of consciousness, chest pain, respiratory distress, seizure, severe respiratory infections and sepsis. 98.2% of physicians and 92.4% of nurses believed that oxygen therapy can be associated with risk. any error in oxygen therapy could lead to worsening of the patient’s status and can even be life-threatening (1). although oxygen is used for the treatment of hypoxia, it can be deadly and should be considered as a drug (2). in our study, 33 (57.98%) physicians and 47 (95.5%) nurses believed that oxygen is a drug. in another study, it was shown that 59% of a hospital’s head nurses believe that oxygen is a drug and should be administered with prescription, while 41% believe that the oxygen is a gas that improves patients’ breathing (14). this study reveals that the knowledge of doctors and nurses on how to correctly use oxygen is fair to weak (in some aspects) and this could have a harmful effect on their performance. it is clear that more emphasis on training in oxygen therapy is necessary during basic training courses for doctors and nurses; and constant and dynamic monitoring on personnel’s learning and performance should be applied. therefore, more consideration and further theoretical and practical training courses in this field seems to be necessary. small sample size and failure to evaluate the attitude and practice of participants are among the limitations of the present study and it is recommended to conduct more studies in this regard. 5. conclusion: the findings showed that the familiarity level of participants with some aspects of o2 therapy such as its indications, necessary measurements and monitoring during therapy, and identifying delivery devices was fair to weak (<80%). therefore, more consideration and further theoretical and practical training courses in this field seems to be necessary. 6. appendix 6.1. acknowledgements many thanks to colleagues for their assistance and consultation in designing the questionnaire. warm thanks to respected doctors and nurses who helped in carrying out our plan and completed the questionnaires with patience; without their assistance this project was not possible. 6.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interest none. 6.4. funding special thanks to clinical research development unit of imam hossein hospital, affiliated to shahid beheshti university of medical sciences, for the registration and financial support. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. goharani et al. 4 references 1. fitzgerald jm, baynham r, powles ac. use of oxygen therapy for adult patients outside the critical care areas of a university hospital. lancet. 1988;1(8592):981-3. 2. bateman nt, leach rm. abc of oxygen. acute oxygen therapy. bmj. 1998;317(7161):798-801. 3. kallstrom tj. aarc clinical practice guideline: oxygen therapy for adults in the acute care facility–2002 revision & update. respir care. 2002;47(6):717-20. 4. al-mobeireek af, abba aa. an audit of oxygen therapy on the medical ward in 2 different hospitals in central saudi arabia. saudi med j. 2002;23(6):716-20. 5. small d, duha a, wieskopf b, et al. uses and misuses of oxygen in hospitalized patients. am j med. 1992;92(6):591-5. 6. howell m. an audit of oxygen prescribing in acute general medical wards. prof nurse. 2001;17(4):221-4. 7. fulmer jd, snider gl. american college of chest physicians (accp)–national heart, lung, and blood institute (nhlbi) conference on oxygen therapy. arch intern med. 1984;144(8):1645-55. 8. guyatt gh, mckim da, weaver b, et al. development and testing of formal protocols for oxygen prescribing. am j respir crit care med. 2001;163(4):942-6. 9. snider gl, rinaldo je. oxygen therapy, oxygen therapy in medical patients hospitalized outside of the intensive care unit. am rev respir dis. 1980;122(5 pt 2):29-36. 10. considine j, botti m, thomas s. the effects of specific educational preparation on emergency nurses’ clinical decisions regarding supplemental oxygen administration. nurs health sci. 2006;8(2):73-80. 11. eastwood gm, reeves jh, cowie bs. nasopharyngeal oxygen in adult intensive care–lower flows and increased comfort. anaesth intensive care. 2004;32(5):670-1. 12. dodd me, kellet f, davis a, et al. audit of oxygen prescribing before and after the introduction of a prescription chart. bmj. 2000;321(7265):864-5. 13. ganeshan a, hon lq, soonawalla zf. oxygen: can we prescribe it correctly eur j intern med. 2006;17(5):355-9. 14. brokalaki h, matziou v, zyga s, et al. omissions and errors during oxygen therapy of hospitalized patients in a large city of greece. intensive crit care nurs. 2004;20(6):352-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion: conclusion: appendix references emergency. 2017; 5 (1): e63 br i e f re p o rt role of serum creatinine phosphokinase in outcome prediction of intoxicated patients; a brief report bita dadpour1, shahrad tajoddini2, elham shaarbaf eidgahi3, mohsen shokouhizadeh4, azam shafahi5∗ 1. medical toxicology research centre, school of medicine, mashhad university of medical sciences, mashhad, iran. 2. neuroscience research center, institute of neuropharmacology, kerman university of medical sciences, kerman, iran. 3. department of biostatistics, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 4. cardiac anesthesia research centre, mashhad university of medical sciences, mashhad, iran. 5. addiction research centre, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: march 2017; accepted: april 2017; published online: 3 april 2017 abstract: introduction: several mechanisms were introduced as causes of serum creatinine phosphokinase (cpk) raise in intoxicated patients. this study aimed to assess the relationship between serum cpk level in the first 24 hours and baseline characteristics as well as outcomes of these patients. methods: this one year retrospective crosssectional study was conducted on all intoxicated patients, who were admitted to a referral toxicology center, northwest of iran, stayed for at least 24 hours and had serum cpk level more than 500 iu/l in the first 24 hours of admission. the relationship between serum cpk level and some baseline and outcome variables were studied using spss version 21. results: 413 patients with the mean age of 34.52 ± 15.24 years were studied (78.7% male). the mean cpk level at the time of presentation to ed was 3702.85 ± 6375.29 iu/l. there was not any significant relationship between presenting cpk level and type of poisoning (p = 0.258), sex (p = 0.587), and age (p = 0.817). the area under the roc curve of cpk in prediction of need for dialysis, need for intensive care unit (icu) admission, and mortality was 0.67 (95% ci: 0.57 – 0.77), 0.60 (95% ci: 0.52 – 0.69), and 0.60 (95% ci: 0.51 – 0.68), respectively. conclusion: based on the finding of present study, there was no significant association between serum cpk level in the first 24 hours and age, sex, and type of poisoning of intoxicated patients and it had poor accuracy in prediction of their need to do dialysis, need for icu admission, and mortality. keywords: poisoning; creatine kinase; rhabdomyolysis; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: dadpour b, tajoddini sh, shaarbaf eidgahi e, shokouhizadeh m, shafahi a. pan vs. role of serum creatinine phosphokinase in outcome prediction of intoxicated patients; a brief report. 2017; 5(1): e63. 1. introduction p oisoning has been known as a major cause of emergency department (ed) admission in developing countries and is responsible for a considerable rate of morbidity and mortality (1, 2). it could be followed by various complications such as rhabdomyolysis (3-5). there are some possible risk factors for inducing rhabdomyolysis in this setting and several mechanisms were introduced as causes of serum cpk raise in intoxicated patients. toxic level of many ∗corresponding author: azam shafahi; addiction research centre, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: +989153065913; email: shafahia1@mums.ac.ir drugs in blood such as antidepressants, isoniazid, antipsychotics, statins, fibrates, and even antihistamines are introduced as predisposing factors of rhabdomyolysis (6). illegal substances could also lead to muscle distress following overdose or withdrawal (7-9). serotonergic syndrome and neuroleptic malignant syndrome may be associated with excessive muscle activity or rigidity followed by a rise in serum cpk level (6, 10). ataxia, seizure and loss of consciousness and further possible prolonged immobility following acute intoxication by many agents put individuals at risk of rhabdomyolysis (6, 10). eizadi-mood et al. showed that cpk > 10000 iu/l is associated with a higher rate of complication and may be an acceptable predictor of poisoned patients’ outcome (6). serum cpk level significantly correlates with severity of clinical presentation following organophosphorus this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. dadpour et al. 2 poisonings (11). this study aimed to assess the relationship between serum cpk level in the first 24 hours and baseline characteristics as well as outcome of intoxicated patients. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on all intoxicated patients presenting to toxicology department of imam reza hospital, mashhad, iran, during one year. the study followed all recommendations of mashhad university of medial sciences ethics committee for descriptive studies. 2.2. participants all intoxicated patients who were admitted to the mentioned toxicology department, stayed for at least 24 hours and had serum cpk level more than 500 iu/l were included, using census sampling. this hospital is a big referral toxicology center in northwest of iran. it is expected that cpk begins to rise 2-12 hours after an acute muscle stress and it will reach its peak plasma level 24 to 36 hours later (12). no confirmed serum cpk level cut off is determined to describe rhabdomyolysis (13). while some studies considered serum cpk level more than 500 iu/l as rhabdomyolysis, others was defined it as a cpk rise more than 5 and 10 times of upper normal limit (12-14). patients with history of trauma, infection, myocardial infarction, and electrolytic disturbances were excluded. no sex or age limitation was considered in this study. 2.3. data gathering a pre-designed checklist that consisted of demographic variables (age, sex), type of poisoning, length of hospital stay, presenting level of consciousness, history of seizure, cpk level in the first 24 hours of presentation to ed, as well as outcomes (need to do dialysis, need for intensive care unit (icu) admission, and mortality) was used for collection of data. a trained medical student was responsible for reviewing the patients’ medical profiles and data gathering. 2.4. statistical analysis data were analyzed using spss version 21. findings were reported as mean ± standard deviation or frequency and percentage. relationship between serum cpk level in the first 24 hours and baseline variables as well as outcome were assessed using chi square or fisher’s exact tests and area under the receiver operating characteristic (roc) curve of cpk in prediction of need to do dialysis, need for icu admission, and mortality were measured with 95% confidence interval (ci). p < 0.05 was considered significant. table 1: the baseline characteristics of participants variable number (%) age (year) < 20 41 (9.9) 20 40 246 (59.6) 40 60 94 (22.8) ≥ 60 32 (7.7) sex male 325 (78.7) female 88 (21.3) type of poisoning neuropsychiatric drugs 206 (52.0) alcohol 133 (33.6) carbone monoxide 13 (3.3) opium 9 (2.3) others 35 (8.8) loss of consciousness yes 53 (12.8) no 360 (87.2) seizure yes 8 (1.9) no 405 (98.1) dialysis yes 24 (5.8) no 389 (94.2) icu admission yes 45 (10.9) no 367 (88.9) mortality yes 38 (9.2) no 375 (90.8) cpk level (iu/l) 500 5000 329 (79.7) 5000 10000 55 (13.3) 1000015000 10 (2.4) 1500020000 4 (1.0) ≥ 20000 15 (3.6) 3. results: 413 patients with the mean age of 34.52 ± 15.24 (2 – 90) years were studied (78.7% male). table 1 shows the baseline characteristics of participants. most of the patients were in the 20 – 40 years age group (59.6%), and were presented to ed following neuropsychiatric drugs intoxication. the mean duration of hospitalization in this series was 4.30 ± 5.64 (1 – 43) days. the mean cpk level during the first 24 hours of presentation to ed was 3702.85 ± 6375.29 (501 – 51220) iu/l. there was not any significant association between serum cpk level in the first 24 hours of presentation and type of poisoning (p = 0.258), sex (p = 0.587), age (p = 0.817), need for icu admission (p = 0.474), and mortality (p = 0.982). out of the 24 patients who underwent hemodialysis, 19 (79.2%) had serum cpk level < 10000 (p = 0.002, pearson’s r = 0.12). the area under the roc curve of cpk in the first 24 hours of admission for prediction of need to do dialysis, need for icu admission, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e63 and mortality was 0.67 (95% ci: 0.57 – 0.77), 0.60 (95% ci: 0.52 – 0.69), and 0.60 (95% ci: 0.51 – 0.68), respectively. 4. discussion based on the findings, there was no significant relation between serum cpk level in the first 24 hours and age, sex, and type of poisoning and it had poor accuracy in prediction of need to do dialysis, need for icu admission, and mortality of intoxicated patients. the most frequent type of poisoning in this study was neuropsychiatric drugs followed by alcohol. this result is similar to the results of eizadi et al. to some extent, but opioids were the most frequent diagnosis in two other similar studies (6, 15, 16). eizadi-mood et al. in a prospective study concluded that serum cpk level might be helpful in prediction of poisoned patients’ outcome. they reported that higher levels of cpk were followed by increased risk of complications and also death (6). in another study that was retrospectively performed on 114 poisoned patients with rhabdomyolysis, the authors found a significant correlation between serum cpk level and creatinine values, and serum creatinine level, in turn, had a significant relationship with death (15). shadnia et al. reviewing the management of 316 patients with valproate intoxication showed the significant correlation of serum cpk level and outcome in univariate analysis, which was omitted in multivariate analysis (17). in contrast, findings of the current study showed that accuracy of serum cpk level in prediction of need for dialysis, need for icu admission, and mortality is poor. based on the findings, about 80% of dialyzed patients in this series were among the patients with serum cpk level < 10000 iu/l. since there is no consensus regarding the best cut off point of cpk in prediction of outcome, we used area under the roc curve for presentation of its accuracy in this regard. it seems that, even though the relationship between serum cpk level and intoxicated patients’ outcomes was reported in some studies, it needs to be confirmed in other studies with larger sample size and multivariate analysis models, considering other probable predictors of outcome. 5. limitation doing the study in a retrospective fashion, not considering other probable predictive factors of outcome, and not considering the time lag between toxic agent consumption and presenting to ed were among the most important limitations of the study, which distort the generalizability of the findings. 6. conclusion based on the finding of present study, there was no significant association between serum cpk level in the first 24 hours and age, sex, and type of poisoning in intoxicated patients and it had poor accuracy in prediction of their need to do dialysis, need for icu admission, and mortality. 7. appendix 7.1. acknowledgements we appreciate the cooperation of all the staff of archive unit of medical records in imam reza hospital, mashhad, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding none. 7.4. conflict of interest none. references 1. asadi r, afshari r. ten-year disease burden of acute poisonings in northeast iran and estimations for national rates. human & experimental toxicology. 2016;35(7):74759. 2. kaya e, yilmaz a, saritas a, colakoglu s, baltaci d, kandis h, et al. acute intoxication cases admitted to the emergency department of a university hospital. world journal of emergency medicine. 2014;6(1):54-9. 3. kidiyoor y, rai s, 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introduction methods results: discussion limitation conclusion appendix references emergency. 2017; 5 (1): e20 or i g i n a l re s e a rc h doing pre-operative investigations in emergency department; a clinical audit muhammad salman rafiq1∗, maria rafiq2, muhammad imran rafiq3 , seema gul salman4, sania hafeez5 1. department of surgery, khyber teaching hospital, peshawar, pakistan. 2. department of obstetrics and gynecology, khyber teaching hospital, peshawar, pakistan. 3. department of cardiology, khyber teaching hospital, peshawar, pakistan. 4. department of obstetrics and gynecology, mardan medical complex, mardan, pakistan. 5. department of obstetrics and gynecology, hayatabad medical complex, peshawar, pakistan. received: january 2016; accepted: august 2016; published online: 9 january 2017 abstract: introduction: pre-operative investigations for emergency surgical patients differ between centers. following established guidelines can reduce unnecessary investigation, cost of treatment and hospital stay. the present audit was carried out to evaluate the condition of doing pre-operative investigations for three common surgical emergencies compared to national institute for health and care excellence (nice) guidelines and local criteria. methods: a retrospective clinical audit of acute-appendicitis, abscess and hernia patients admitted to the emergency department was carried out over a one-year period from july 2014 to july 2015. data of laboratory investigations, their indication, cost and duration of hospital stay was collected and compared with nice-guidelines. results: a total of 201 patients were admitted to the emergency department during the audit period. these included 77(38.3%) cases of acute-appendicitis, 112 (55.7%) cases of abscesses, and 12 (6%) cases of hernia. investigations not indicated by nice-guidelines included 42 (20.9%) full blood counts, 29 (14.4%) random blood sugars, 26 (12.9%) urea tests, 4 (2%) chest x-rays, 13 (6.5%) electrocardiographs, and 58 (28.9%) urine analyses. these cost 25,675 rupees (245.46 dollars) in unnecessary investigation costs and 65.7 days of additional hospital stay. conclusion: unnecessary investigations for emergency surgical patients can be reduced by following nice-guidelines. this will reduce workload on emergency services, treatment costs and the length of hospital stay. keywords: clinical audit; management audit; emergency treatment; emergencies © copyright (2017) shahid beheshti university of medical sciences cite this article as: rafiq m-s, rafiq m, rafiq m-i, salman s, hafeez s. doing pre-operative investigations in emergency department; a clinical audit. 2017; 5(1): e20. 1. introduction s urgical management is dependent upon laboratory and radiological investigations, and treatment guidelines and scoring systems usually rely on their findings (1). these investigations are associated with some adverse outcome (2). all radiological evaluations expose subjects to variable doses of radiation and may require contrast, which is associated with its own adverse effects. on the other hand, hematological investigations are associated ∗corresponding author: muhammad salman rafiq; surgical unit, khyber teaching hospital, peshawar, postal code 25000, kpk, pakistan. phone; cell: 0092-0346-9035574 . email: drsalmanrafiq@hotmail.com with the risk of infection transmission, needle stick, hemorrhage, and etc. (3). whereas laboratory investigations are relatively cheaper and are usually prescribed by junior medical personnel, radiological ones are costly and are usually prescribed by consultants or senior medical personnel. there are no fixed guidelines of prescription for these investigations in most centers. these differences are responsible for investigations being performed in large numbers, more frequently, and in some cases, unnecessarily (4). in an emergency department, investigation services are usually being utilized at any given instance. these slots are simultaneously used by various departments in addition to emergency surgical services. a careless attitude towards laboratory investigations will result in unnecessary investigations, increase in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rafiq et al. 2 treatment costs, straining of laboratory services, increase in hospital stay and patient mismanagement. such practices are more prevalent in the absence of guidelines (5). presence and implementation of guidelines outlining investigations for any given condition reduces such unnecessary testing. this reduces the cost of treatment as shown by previous studies (5, 6). international and local guidelines specifically created for pre-operative emergency surgical management are lacking. the national institute for health and care excellence (nice) guidelines for pre-operative management of surgical patients were created for elective cases (7). these can be applied to emergency surgeries because they are based on a simple grading of surgical procedures. based on the above mentioned, the present audit was carried out to evaluate the condition of doing pre-operative investigations for three common surgical emergencies compared to national institute for health and care excellence (nice) guidelines and local criteria. 2. method 2.1. study design a retrospective clinical audit of 201 randomly selected patients of three common surgical emergencies, admitted to the emergency department of khyber teaching hospital, was carried out over a one-year period from july 2014 to july 2015. these included patients of acute appendicitis, acute hernia and abscesses requiring emergency surgery. approval of the hospital’s ethical and research committees was obtained. 2.2. participants all patients over the age of 18 years of both male and female gender with diagnosis of acute appendicitis, abscess or hernia presenting to emergency department and requiring emergency surgery were included. 2.3. data gathering data was collected, using a printed preform, from the treatment charts and emergency outpatient sheets. data of laboratory and radiological investigations carried out for the three mentioned surgical emergencies was collected for each patient. indicated investigations by nice guidelines and local criteria were determined and inappropriate investigations were defined as investigations that were not indicated or performed more than once without reason. if investigations were inappropriately carried out, the resultant cost and increase in duration of hospital stay were calculated. since local criteria and nice guidelines differed in all instances for indication of each pre-operative emergent investigation, data regarding indication of doing investigation in both instances was collected. local criteria include a total of 12 investigations compared to 6 investigations of the nice guidelines. an additional nice investigation i.e. hemostasis was not made part of pre-operative testing as it was not indicated in any of the cases. these are detailed below in audit standards and local criteria sections. 2.4. audit standards in 2003, nice published guidelines for the routine preoperative investigations of elective surgery (7). these guidelines were used as the standards for comparison in the present study (panel 1 to 3). these guidelines declare the indications of seven commonly performed investigations include: chest x-ray; electrocardiography; complete blood count; hemostasis profile [bleeding time, clotting time, platelets count, prothrombin time (pt), partial thromboplastin time (ptt), international normalized ratio (inr)]; renal function tests (urea, creatinine); random blood sugar; and urine analysis. the guidelines include hemostasis as a required investigation but it was not included in this audit where pre-operatively hemostasis assessment is rarely indicated for the studied surgical emergencies. for abscesses, which require surgical incision and drainage, categorized as grade 1 or minor surgery, investigations should include as shown in panel 1. for cases of right lower quadrant pain clinically diagnosed as acute appendicitis or cases presenting as acute obstructed or strangulated hernia, requiring emergency surgery, both in the category of grade 2 or intermediate surgery, investigations should include as shown in panel 2. for cases of acute obstructed or strangulated hernia, requiring emergency surgery, considered as grade 3 or major surgery, investigations should include as shown in panel 3. for acute hernia, major surgery was defined as cases clinically determined pre-operatively with a strong possibility of bowel gangrene or requiring resection and anastomosis. in each instance, a pre-operative test should be sampled and the result obtained only once, unless it is inadequately sampled or reported or there is doubt about the result requiring a repeat sampling and testing. 2.5. local criteria (hospital guideline) based on our local criteria pre-operative management of the three mentioned surgical emergencies included 12 investigations. these investigations and their costs were as follows: complete blood count (cbc), 45 rupees (43 cents); random blood sugar (rbs), 45 rupees (43 cents); urea, 45 rupees (43 cents); serum electrolytes, 100 rupees (96 cents); liver function tests (lfts), 120 rupees (1.15 dollar); serum amylase, 45 rupees (43 cents); c-reactive protein (crp), 200 rupees (1.91 dollar); ultrasonography (usg), 220 rupees (2.1 dollars); chest x-ray with non-digital device (cxr), 50 rupees (48 cents); electrocardiogram (ecg), 50 rupees (48 cents); viral markers (non-elisa including hepatitis b, c and hiv ), 100 rupees (96 cents); and urine analysis (u/a), 45 rupees this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e20 panel 1: required pre-operative investigations for grade 1 or minor surgeries investigations age ( years) 18 to < 40 40 to < 60 60 to < 80 80 < chest x-ray no no no no electrocardiography no consider consider yes complete blood count no no consider consider hemostasis profile no no no no renal function tests no no consider consider random blood sugar no no no no urine analysis consider consider consider consider panel 2: required pre-operative investigations for grade 2 or intermediate surgeries investigations age ( years) 18 to < 40 40 to < 60 60 to < 80 80 < chest x-ray no no no no electrocardiography no consider consider yes complete blood count no consider yes yes hemostasis profile no no no no renal function tests no no consider consider random blood sugar no consider consider consider urine analysis consider consider consider consider panel 3: required pre-operative investigations for grade 3 or major surgeries investigations age ( years) 18 to < 40 40 to < 60 60 to < 80 80 and > chest x-ray no no consider consider electrocardiography no consider yes yes complete blood count yes yes yes yes hemostasis profile no no no no renal function tests consider consider yes yes random blood sugar consider consider consider consider urine analysis consider consider consider consider (43 cents). for abscesses, which require surgical incision and drainage, investigations should include: • complete blood count, viral markers, and if indicated chest x-ray, ecg, ultrasonography of abscess cavity for patients younger than 40 years • complete blood count, viral markers, chest x-ray, ecg, and if indicated rbs, renal function, electrolytes and ultrasonography of abscess cavity for patients ≥ 40 years for cases of right lower quadrant pain clinically diagnosed as acute appendicitis requiring emergency surgery, investigations should include: • complete blood count, viral markers, ultrasonography of abdomen and pelvis for patients younger than 40 years • complete blood count, viral markers, ultrasonography of abdomen and pelvis, chest x-ray and ecg for patients ≥ 40 years for cases presenting as acute obstructed or strangulated hernia, requiring emergency surgery, investigations should include: • complete blood count, viral markers, ultrasonography of abdomen and pelvis, urea, serum electrolytes, and if indicated chest and/or abdominal x-ray, ecg, and serum amylase for patients younger than 40 years • complete blood count, viral markers, ultrasonography of abdomen and pelvis, urea, serum electrolytes, chest x-ray, ecg, and if indicated serum amylase for patients ≥ 40 years serum amylase is prescribed to rule out gastro intestinal pathology such as pancreatitis, hollow viscus perforation and other causes. 2.6. statistical analysis all data were recorded in the statistical software spss version 20. comparison was made with nice guidelines and local criteria for laboratory and radiological investigations for acute appendicitis, abscesses and hernia requiring emerthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rafiq et al. 4 table 1: condition of doing preoperative investigations based on local criteria and national institute for health and care excellence (nice) guidelines investigation local criteria nice guidelines indicated performed #inappropriate indicated inappropriate cost rupees(dollar) additional stay (minutes) cbc 173(86.1%) 173(86.1%) 38(18.9%) 42(20.9%) 8,415 (80.45) 41390 rbs 82(40.8%) 82(40.8%) 48(23.9%) 29(14.4%) 4,950 (47.32) 20140 urea 82(40.8%) 82(40.8%) 15(7.5%) 26(12.9%) 3,195 (30.55) 17490 electrolytes 21(10.4%) 21(10.4%) 12(6%) * * * lfts 1(0.5%) 1(0.5%) 0(0%) * * * amylase 9(4.5%) 9(4.5%) 0(0%) * * * crp 0(0%) 0(0%) 0(0%) * * * sonography 123(61.2%) 123(61.2%) 24(11.9%) * * * cxr 38(18.9%) 38(18.9%) 2(1%) 4(2%) 2,250 (21.51) 2290 ecg 73(36.3%) 73(36.3%) 17(8.5%) 13(6.5%) 4,300 (41.11) 4490 viral profile 201(100%) 201(100%) 32(15.9%) * * * urine analysis 91(45.3%) 91(45.3%) 11(5.5%) 58(28.9%) 2,565 (24.52) 8750 total 25,675(245.46) 94550 * represents investigations which are not part of nice guidelines. # represents cases where investigations were ordered multiple times when indicated only once. cbc: complete blood count; rbs: random blood sugar; crp: c reactive protein; cxr: chest x ray; ecg: electrocardiography. gency surgery using chi square or fisher’s exact tests. data were expressed as frequency and percentage or mean ± standard deviation. 3. results a total of 201 patients were analyzed. the mean age of the patients was 48.26 ± 18.72 years. there were 77 (38.3%) cases of acute appendicitis, 112 (55.7%) cases of abscesses and 12 (6%) cases of acute hernia. condition of doing preoperative investigations based on local criteria and national institute for health and care excellence (nice) guidelines is shown in table 1. rbs was the most in-appropriately performed investigation with 48 (23.9%) cases where it was performed twice pre-operatively, followed closely by cbc in 38 (18.9%) cases. viral markers were checked for all cases whereas crp was not performed in any case. the greatest difference between local and nice guideline was for cbc; 173 (86.1%) cases as per local criteria compared to only 42 (20.9%) cases per nice guidelines. 3.1. patient’s cost cbc was responsible for the largest cost of 8,415 rupees (80.45 dollars) for inappropriate testing. inappropriate testing leading to additional costs for rbs, urea, cxr, ecg and urine analysis was calculated at 4950 rupees (47.32 dollars), 3195 rupees (30.55 dollars), 2250 rupees (21.51 dollars), 4300 rupees (41.11 dollars) and 2565 rupees (24.52 dollars., respectively. the total cost for all of these was 25,675 rupees (245.46 dollars). 3.2. duration of hospital stay cbc was responsible for the largest contribution to unnecessary hospital stay at 41390 minutes, which equals to a total of 28.7 days. the smallest contribution to unnecessary hospital stay was due to cxr at 2565 minutes or 1.8 days. the total number of unnecessary hospital stay was calculated to be 94550 minutes (65.7 days). 4. discussion clinical practice guidelines are end results of large multicenter studies and multi-disciplinary approaches (8). the nice guidelines, related to clinical practice, were created after multiple studies including clinical audits (7). this resulted in the proposal of the 2003 nice guideline for the preoperative assessment of surgical patients. originally, these guidelines were created for elective surgery cases but they can be applied to emergency surgeries as well. this is because the nice guidelines are classified on a simple grading of surgeries as grade 1 to 4 (7). health system in pakistan is not organized on central uniform guidelines. tertiary care hospitals usually follow local criteria, foreign clinical guidelines or a combination of both. however, no strict guidelines are followed for doing preoperative investigation for surgical emergencies. local practices for emergency surgery, such as acute appendicitis, abscesses requiring surgical treatment and obstructed or strangulated hernias, are not outlined (9). differences were expected between local criteria and nice guidelines. an important difference was the fewer number of investigations by nice standards; seven compared to 12 for local criteria. nice utilizes tests for hemostasis, but for the three surgical processes included in the audit, they are rarely this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e20 required. nice does not include some investigations in its guidelines, which are used in local criteria. these include electrolytes, lft, amylase, crp, viral markers and ultrasonography. these were included only as part of local criteria. the most important local criteria not included in nice is viral markers. local criteria requires that testing for hepatitis b, c and hiv be carried out in every case (10). the audit fell short in indication for various investigations. based on local criteria, cbc was indicated in 173 (86.1%) cases, whereas it was only indicated in 42 (20.9%) cases based on nice guidelines. this represents a difference of 131 cases or 65.2%. difference between local and nice guidelines for checking preoperative rbs, urea, cxr, ecg and urine r/e were 26.4%, 27.9%, 16.9%, 29.8% and 16.4%, respectively. in many cases, investigations were ordered multiple times when they were required only once for pre-operative assessment. rbs was the most commonly abused investigation, which was inappropriately performed in 48 (23.9%) cases. this was closely followed by cbc with 38 (18.9%) cases. multiple investigation instances for urea, cxr, ecg and urine analysis were 15 (7.5%), 2 (1%), 17 (8.5%) and 11 (5.5%), respectively. analysis of data showed that in all instances of multiple investigations, they were performed only twice. 4.1. cost multiple instances and inappropriately indicated investigations based on nice guidelines resulted in unnecessary expenditure to the hospital. the greatest cost of unnecessary expenditure was caused by cbc at 8,415 rupees (80.45 dollars). this was followed by rbs at 4,950 rupees (47.32 dollars). this resulted in a total loss of 25,675 rupees (245.46 dollars) of unnecessary investigations. 4.2. hospital stay inappropriate testing was responsible for unnecessary and prolonged hospital stay. the largest contribution to unnecessary hospital stay was caused by cbc closely followed by rbs, urea, cxr, ecg, and urine analysis, respectively. the total time in terms of unnecessary hospital stay was calculated to be 94550 minutes (65.66 days). there are a number of factors responsible for unnecessary investigations being ordered for emergency surgical patients. in emergency surgical management, almost all investigations are ordered by junior doctors and sometimes nurses who are not involved in clinical assessment or operative treatment. there are no evidencebased guidelines for investigation of emergency surgical patients. nice guidelines were originally proposed for elective surgical cases. in many instances, investigations are repeated pre-operatively without a reason or by mistake. there are instances where these are repeated because first samples taken and reports provided are by external labs, which are not part of the hospital. investigations not related to the disease process and its management are responsible for a sizeable portion of the audit shortcomings. cbc might not be required in cases of simple incision and drainage where systemic signs are absent. urea was ordered in young patients and cases of simple abscesses. other investigations ordered for simple abscesses, which were not indicated by nice guidelines, included ultrasonography, cxr, ecg and urine analysis. cases where the presenting disease process was associated with abnormal incidental findings in other systems were responsible for some of these unnecessary investigations. this accounted for some of the cases where for example urea and electrolytes were ordered for abscess or lfts, cxr and ecg for young patients of acute appendicitis, etc. this aspect requires a separate audit because it contributes to unnecessary investigations, cost and hospital stay. investigations, which are not part of nice guidelines but are required by evidencebased recommendations for all admitted patients, require a separate audit. these include crp and viral markers of all admitted patients for hepatitis b, c and hiv. serum amylase also falls in this category. 4.3. recommendations to overcome the shortcoming in the audit, the following recommendations are made: • posters about nice guidelines for pre-operative management of surgical cases should be set up in the emergency department. • staff of the emergency department especially junior doctors and nurses should be educated about nice guidelines and the findings of this audit through presentations. • investigations ordered for all cases should follow nice guidelines. • investigations should not be repeated pre-operatively unless indicated. • investigations carried out in other setups before admission should be discussed with seniors to avoid multiple investigations. 5. conclusions based on the results of the present audit, investigations ordered without indication, and in some cases multiple times, were responsible for unnecessary treatment cost and prolonged hospital stay. following nice guidelines or establishing evidence-based local guidelines can reduce and prevent these mistakes and costs. 6. appendix 6.1. acknowledgements none this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rafiq et al. 6 6.2. authors contributions conceived and designed the experiments: msr, mr, mir, sgs, sh. analyzed the data: msr, mr, mir, sgs. wrote the paper: msr, mr, mir, sgs. data collection: msr, mr, mir, sh, sgs, sh. critical revision: msr, mr, mir. all authors read and approved the final manuscript. 6.3. funding support no funding from any source was utilized for this study. 6.4. conflict of interest we wish to confirm that there are no known conflicts of interest associated with this publication. references 1. zambouri a. preoperative evaluation and preparation for anesthesia and surgery. hippokratia. 2007;11 (1):13-21. 2. kumar m. overuse of various radiological and pathological investigations: should we be safe or sorry journal of family medicine and primary care. 2014;3(2):171. 3. czoski-murray c, jones ml, mccabe c, claxton k, oluboyede y, roberts j, et al. what is the value of routinely testing full blood count, electrolytes and urea, and pulmonary function tests before elective surgery in patients with no apparent clinical indication and in subgroups of patients with common comorbidities: a systematic review of the clinical and cost-effective literature. 2012. 4. miyakis s, karamanof g, liontos m, mountokalakis td. factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. postgraduate medical journal. 2006;82(974):823-9. 5. van heyningen c, simms p. guidelines for out-ofhours clinical chemistry investigations. clinical chemistry. 1990;36(12):2151-2. 6. pennycook a. are blood tests of value in the primary assessment and resuscitation of patients in the a& e department postgraduate medical journal. 1995;71(832):81-5. 7. excellence nifc, britain g. preoperative tests: the use of routine preoperative tests for elective surgery: national institute for clinical excellence; 2003. 8. brophy jm. multicenter trials, guidelines, and uncertainties–do we know as much as we think we do international journal of cardiology. 2015;187:600-3. 9. islam a. health sector reform in pakistan: why is it needed jpma the journal of the pakistan medical association. 2002;52(3):95-100. 10. weiss es, cornwell ee, wang t, syin d, millman ea, pronovost pj, et al. human immunodeficiency virus and hepatitis testing and prevalence among surgical patients in an urban university hospital. the american journal of surgery. 2007;193(1):55-60. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction method results discussion conclusions appendix references archives of academic emergency medicine. 2022; 10(1): e75 ca s e re p o rt cocaine and volatile nitrite–induced methemoglobinemia; a case report and treatment approach review milena ribeiro paixão1∗, tarso augusto duenhas accorsi1, luis felipe lopes prada1, lucas zoboli pocebon1, karine de amicis lima1, karen francine köhler1, leandro santini echenique2, josé leão de souza júnior1 1. emergency department, israelita albert einstein hospital, sao paulo, brazil. 2. cardiology department, israelita albert einstein hospital, sao paulo, brazil. received: july 2022; accepted: august 2022; published online: 21 september 2022 abstract: cyanosis is typically a sign of a potentially life-threatening condition in the emergency department and requires immediate workup and treatment. this case report highlights the diagnostic reasoning and clinical approach to cocaineand volatile nitrite–induced methemoglobinemia (mhg). mhg is a rare, life-threatening cause of cyanosis. the diagnosis must be suspected in the emergency department in the presence of hypoxia and cyanosis disproportionate to cardiopulmonary repercussions and refractory to oxygen supplementation. acquired causes are more prevalent than genetics, and recreational drugs should be highly suspected. despite the rarity of this situation, cyanosis precipitants and the specificities of each hemoglobinopathy are reviewed in this article. keywords: methemoglobinemia; cocaine; nitrites; emergency medicine; case reports cite this article as: ribeiro paixão m, duenhas accorsi ta, lopes prada lf, zoboli pocebon l, amicis lima kd, et al. cocaine and volatile nitrite–induced methemoglobinemia; a case report and treatment approach review. arch acad emerg med. 2022; 10(1): e75. https://doi.org/10.22037/aaem.v10i1.1753. 1. introduction acute cyanosis is a singular, potentially life-threatening sign and requires a fast emergency department (ed) approach. the most common disorders that accompany cyanosis are pulmonary and cardiovascular diseases due to systemic desaturation or increased oxygen extraction. methemoglobinemia (mhg) is a rare, potentially fatal cause of cyanosis and should be considered in patients with cyanosis and hypoxia (1-3). this report presents an uncommon case of cocaineand volatile nitrite–induced mhg in a patient admitted to the ed of israelita albert einstein hospital, são paulo, brazil. further, this report aims to clarify the diagnostic approach to acute cyanosis. 2. case presentation a previously healthy 31-year-old male patient presented to the emergency department with dizziness, sweating, anxiety, ∗corresponding author: milena ribeiro paixão; av. albert einstein, 627. bloco b, 2º andar, secretaria da unidade de pronto atendimento, sao paulo – sp. zip code 05652-900 brazil. phone: +55 11 2151-1233. email: milena.paixao@einstein.br, orcid: https://orcid.org/0000-0002-1565-3915. muscle spasms, shortness of breath, and bluish hands and lips. the symptoms had started two hours before admission, about 90 minutes after using inhaled cocaine and "poppers" (volatile nitrites). the patient reported that it was the second time he had used cocaine in his lifetime, had used volatile nitrites, and had used cocaine and poppers simultaneously for the first time. on admission, the vital signs were as follows: blood pressure of 138/75 mmhg, heart rate of 89 beats per minute, respiratory rate of 20 breaths per minute, and oxygen saturation of 88–90% while breathing in ambient air. he had cyanotic lips, hands, and feet but no remarkable findings on cardiopulmonary examination. the electrocardiogram (ecg) performed on admission showed an apiculate t wave in v3v4 derivation, normalized in subsequent minutes (figure 1, left). the chest radiograph showed normal lung tissue and cardiac area (figure 1, right). on arrival and after two hours, the troponin levels were < 40 pg/ml (within the normal range). admission laboratory tests showed hemoglobin 17.1g/dl, leukocytes 13,760 µl, neutrophils 12,246, platelets 298,000 µl, and creatinine, sodium, potassium, calcium, d-dimer, and nt-probnp within normal range. there was no improvement in oxygen saturation despite a progressive offer of supplementary oxygen. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ribeiro paixão et al. 2 table 1: blood gas analysis during emergency department care variables on admission after treatment∗ a normal range arterial venous 1mg/kg& 2mg/kg# ph 7.407 7.395 7.457 7.417 7.35–7.45 pco2 (mmhg) 35.0 36.6 31.7 36.8 35–45 po2 (mmhg) 62.4 25.5 297 74.1 80–90 a / 41–50v base excess (mmol/l) -1.8 -1.8 -0.2 -0.3 -2.0–2.0 bicarbonate (mmol/l) 21.6 22.0 22.1 24.4 24–28 oxygen saturation (%) 91.3 59.4 98.8 93.9 96-97 a /40-70v methemoglobin (%) 41.3 43.8 13.2 1.3 <1.5 *: treatment was done with methylene blue injection. #samples was collected while patient was breathing ambient air. & sample was collected while patient was receiving 15l/min of supplemental oxygen with non-rebreathing mask. pco2 = partial pressure of carbon dioxide, po2 = partial pressure of oxygen, a: arterial blood sample, v: venous blood sample. figure 1: a) admission electrocardiogram showing apiculate t wave in v3-v4 derivation, b) spontaneously normalized electrocardiogram in subsequent minutes (left). chest radiograph with normal lung tissue and cardiac area (right). cardiovascular causes of cyanosis were unlikely as the patient had no chest pain, heart sounds were normal, shock signs were absent, ecg abnormalities (v3-v4 apiculate t wave) did not progress to st-elevation myocardial infarction, and troponin, nt-probnp, and d-dimer levels were normal. pulmonary diseases were also implausible since there were no history or pulmonary findings suggestive of bronchospasm, pulmonary embolism, pneumothorax, upper obstruction, aspiration, and infectious or chronic pulmonary diseases. mhg was suspected, especially after no improvement in saturation with progressive high oxygen offer. his venous and arterial blood samples were dark red. the arterial blood gas (table 1) was readily available and confirmed methemoglobin levels > 40% (normal range < 1.5%). he was treated with methylene blue at 1 mg/kg for 20 minutes with clinical improvement, and the methemoglobin level decreased to 13%. another dose of 1 mg/kg was administered after one hour, with symptom resolution and methemoglobin level of 1.3%. the patient was discharged asymptomatic on the third day of hospitalization after performing echocardiogram and holter monitoring, the results of which were normal. 3. discussion mhg is potentially fatal because it impairs the oxygencarrying capacity of blood by converting iron species from this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e75 figure 2: diagnosis and management of central cyanosis in the emergency department. table 2: hemoglobinopathies’ characteristics character methemoglobin carboxyhemoglobin sulfhemoglobin precipitants hereditary, medicine, recreational, drugs food poisoning inhalation of carbon monoxide during fires and the burning of gasoline, wood, coal, kerosene, and other fuels in poorly ventilated areas. induction by drugs (i.e., dapsone, sulphonamides, phenazopyridine) blood color dark red cherry red green diagnosis measurements through co-oximetry or blood gas measurements through co-oximetry or blood gas measurement through co-oximetry, spectrophotometry, or gas chromatography treatment methylene blue, ascorbic acid, oxygen, supplementation high flow or hyperbaric oxygen support (no antidote) resolution after erythrocyte turnover (definitively linked to hemoglobin), exchange transfusion in severe cases the reduced ferrous (fe 2+) to the oxidized ferric (fe 3+) form in the circulation of hemoglobin. the latter is unable to adhere to and transport oxygen. thus, the o2 offered to the tissues is decreased, and the ferric heme shifts the oxyhemoglobin curve to the left (2). in addition to cyanosis, other symptoms of mhg range from headaches, blurred vision, irritability, lack of short-term memory, agitation, combativeness, confusion, lethargy, unconsciousness, and respiratory distress (4, 5). recreational drugs that cause mhg include e-cigarettes, volatile nitrites (known as "poppers” because of the sound the small glass containing the liquid makes on being crushed between the fingers), cocaine, heroin, and other substances used as diluting adulterants (6, 7). less commonly, exogethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ribeiro paixão et al. 4 nous intoxication with antifreeze, naphthalene balls, solvents, and pesticides were also reported as possible causes of mhg (8, 9). cocaine is widely consumed worldwide, with an estimated 20 million current users (10). in the emergency department, cocaine is responsible for 30% of all drug-related evaluations (11). though cocaine itself is not a usual precipitant for mhg, its most frequent diluents are. these include phenacetin, lidocaine, benzocaine, and procaine (12-14). the recreational use of volatile nitrites ("poppers") became popular since the 1970s, especially in the gay community, because of its property of relaxing smooth muscles, such as the throat and anal sphincter, in addition to inducing euphoria and warmth. meanwhile, undesirable effects include headaches, dizziness, anxiety, ataxia, loss of vision (maculopathy), and mhg (15, 16). an estimated 3.3% of the adults in the united states have used poppers. in the gay man population, the prevalence is estimated at 35% (17). mhg can also be acquired through medicine and food. medicines that can precipitate mhg are local and inhaled anesthetics like lidocaine, benzocaine, prilocaine, and nitric oxide; antimalarial agents such as chloroquine and primaquine; dapsone, used in hansen’s disease, as prophylaxis in pneumocystis pneumonia in hiv, and present in some anti-acne agents; and acetaminophen (18-20). food items include choy sum, fennel, root vegetables such as carrots and beetroots, meat and cheese contaminated with high nitrate content to preserve it longer, and possibly well water. hereditary mhg is a rare autosomal recessive disorder related to cytochrome b5 reductase deficiency. because of the decrease in the enzyme that reduces ferric heme to ferrous heme, the conversion of methemoglobin to hemoglobin becomes difficult. in hemoglobin m disease, a dominant disorder leads iron to connect to phenolate, a complex that makes the reduction of ferric heme difficult. the final form of inherited mhg is cytochrome b5 deficiency, an unlikely disorder that disables the electron donation for methemoglobin conversion to hemoglobin (21, 22). a structured reasoning flow from diagnosis to treatment for patients with central cyanosis in the ed is proposed in figure 2. the starting point is the immediate work to differentiate cardiovascular and pulmonary diseases, and hemoglobinopathies. the symptoms are similar among the hemoglobinopathies (table 2) (1-5, 23, 24). in these cases, typically, there is no improvement in oxygen saturation even with a progressive increase in oxygen supply; however, this is insufficient to exclude cardiovascular and pulmonary conditions. recently some colleagues have reported a case of mhg presumably induced by cocaine adulterants. they reinforced the importance of the laboratory routinely reporting methemoglobin and carboxyhemoglobin levels or at least reporting them when values are above the normal range even when not requested (25). our hospital implemented the routine of alerting the team responsible for the patient about all the non-requested altered findings in the blood gas analysis (hemoglobin, glucose, creatinine, electrolytes, and lactate) to prevent adverse events due to lack of diagnosis. 4. limitations because of the lack of tests to define the precipitant of mhg, we acknowledge that the precipitant could have been only volatile nitrite or cocaine diluents. however, knowing that the patient used these recreational drugs alone in the past without complications and that both can be related to mhg, we presumed the precipitant was their combination. 5. conclusion mhg is a rare, life-threatening cause of cyanosis. the diagnosis must be suspected in the emergency department in the presence of hypoxia and cyanosis disproportionate to cardiopulmonary repercussions and refractory to oxygen supplementation. acquired causes are more prevalent than genetics, and recreational drugs should be highly suspected. 6. declarations 6.1. acknowledgments integrate investigators (einstein emergency research team). 6.2. authors’ contributions all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. conception, planning, analysis, and interpretation of data: mrp, tada. data collection: lflp, lzp, lse, mrp. writing of the article or its critical intellectual review: mrp, tada, kal, kfk. responsibility for final review and approval for publication: all author. 6.3. funding and support none. 6.4. conflict of interest authors have no conflict of interest. 6.5. ethical consideration and consent the study and consent waiver were approved by the hospital israelita albert einstein review board (caae protocol number: 52261321.0.0000.0071). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e75 references 1. skold a, cosco dl, klein r. methemoglobinemia: pathogenesis, diagnosis, and management. south med j. 2011;104(11):757-61. 2. mansouri a, lurie aa. concise review: methemoglobinemia. am j hematol. 1993;42(1):7-12. 3. do nascimento ts, pereira ro, de mello hl, costa j. methemoglobinemia: from diagnosis to treatment. rev 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[hereditary methemoglobinemias]. arch pediatr. 2000;7(5):513-8. french. 23. gharahbaghian l, massoudian b, dimassa g. methemoglobinemia and sulfhemoglobinemia in two pediatric patients after ingestion of hydroxylamine sulfate. west j emerg med. 2009;10(3):197-201. 24. chenoweth ja, albertson te, greer mr. carbon monoxide poisoning. crit care clin. 2021;37(3):657-72. 25. shelton d, dashi g, cheung m, sindall t. case report of methemoglobinemia: an illustration that it is time to report all results with arterial and venous blood gas result reporting. j emerg med. 2020;58(2):e51-e4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e10 or i g i n a l re s e a rc h clinical, laboratory and imaging characteristics of hospitalized covid-19 patients with neurologic involvement; a cross-sectional study ali zare dehnavi1, mohammadreza salehi2, mehran arab ahmadi3, mohammad hossein asgardoon4, farzad ashrafi5, nasrin ahmadinejad3, atefeh behkar4, ramin hamidi farahani6, hassan hashemi3, abbas tafakhori7, hamze shahali8, mohammad rahmani7, alireza ranjbar naeini1∗ 1. department of neurology, school of medicine, aja university of medical sciences, tehran, iran. 2. infectious diseases and tropical medicines department, tehran university of medical sciences, tehran, iran. 3. advanced diagnostic and interventional radiology research center, tehran university of medical sciences, tehran, iran. 4. school of medicine, tehran university of medical sciences, tehran, iran. 5. functional neurosurgery research center, shohadaye tajrish neurosurgical center of excellence, shahid beheshti university of medical sciences, tehran, iran. 6. department of infectious disease, aja university of medical sciences, tehran, iran. 7. department of neurology, school of medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 8. department of aerospace and sub aquatic medicine, aja university of medical sciences, tehran, iran. received: december 2021; accepted: december 2021; published online: 30 january 2022 abstract: introduction: although neurologic involvement and neuroimaging abnormalities have been frequently identified in covid-19 patients, the underlying factors remain unclear. in this study, we assessed the association of the neurological manifestations and neuroimaging features of hospitalized covid-19 patients with their clinical, laboratory, and imaging characteristics. methods: this multicenter cross-sectional study was conducted between september 2020 and march 2021 at two large academic hospitals in tehran, iran. we used census sampling from medical records to enroll hospitalized patients with a positive covid-19 polymerase chain reaction (pcr) test who underwent brain imaging due to presenting any acute neurologic symptom during hospital stay. results: of the 4372 hospitalized patients with covid-19, only 211 met the inclusion criteria (35.5% with severe infection). central nervous system and psychiatric manifestations were significantly more common in severe cases (p ≤ 0.044). approximately, 30% had a new abnormality on their neuroimaging, with ischemic (38/63) and hemorrhagic (16/63) insults being the most common. the most frequent reasons that provoked cranial imaging were headache (27%), altered consciousness (25.6%), focal neurologic signs (19.9%), and delirium (18%). analysis revealed a positive correlation for age, neutrophilia, lymphopenia, erythrocyte sedimentation rate (esr), and c-reactive protein (crp) with the emergence of neuroimaging abnormalities (p ≤ 0.018). in addition, patients with new neuroimaging abnormalities had a significantly higher lung ct score than those without any pathologic findings (11.1 ± 4.8 vs. 5.9 ± 4.8, p < 0.001). conclusion: approximately 30% of the study population had various acute neuroimaging findings. the lung ct score, neutrophil count, and age were strong predictors of acute neuroimaging abnormalities in hospitalized covid-19 patients. keywords: covid-19; neurology; neurologic manifestations; neuroimaging; tomography, x-ray computed; magnetic resonance imaging; risk factors cite this article as: zare dehnavi a, salehi m, arab ahmadi m, asgardoon m h, ashrafi f, ahmadinejad n, behkar a, hamidi farahani r, hashemi h, tafakhori a, shahali h, rahmani m, ranjbar naeini a. clinical, laboratory and imaging characteristics of hospitalized covid-19 patients with neurologic involvement; a cross-sectional study. arch acad emerg med. 2022; 10(1): e10. https://doi.org/10.22037/aaem.v10i1.1507. ∗corresponding author: alireza ranjbar naeini; aja university of medical sciences, etemad zadeh street, fatemi-gharbi street, tehran, iran. / postal code: 1411718541, e-mail: a.ranjbar.naeini@ajaums.ac.ir, tell: 02186096350, orcid: http://orcid.org/0000-0002-3150-6093. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zare dehnavi et al. 2 1. introduction covid-19 has been declared a public health emergency of international concern by the world health organization (who)(1). according to who statistics, to date (december 20, 2021), this disease has infected roughly 272 million people worldwide and has led to more than 5 million deaths (2). according to who statistics, iran is one of the top 20 nations with the highest prevalence of covid-19, with approximately 6.2 million individuals infected and 130,000 deaths documented so far (december 20, 2021) (2). covid-19 can have a variety of clinical manifestations, from asymptomatic to death (3). with the increase in covid-19 cases globally, many extra-pulmonary manifestations of this disease, such as neurologic ones, have been documented (3, 4). different investigations have found that the prevalence of at least one new-onset neurological manifestation linked to covid19 infection is highly variable, ranging from around 10% to more than 80% (5-7). in addition, neuropsychiatric problems such as delirium have been frequently documented in hospitalized patients, and linked to a higher mortality rate in covid-19 cases (8, 9). several studies have also documented neuroimaging abnormalities in patients with covid-19, including ischemic and hemorrhagic infarction, cerebral venous thrombosis, demyelinating disorders such as acute disseminated encephalomyelitis (adem), meningitis, encephalomyelitis, acute hemorrhagic necrotizing encephalopathy (ane), and hemorrhagic posterior reversible encephalopathy syndrome (pres)(4, 10-12). due to the neurological symptoms that emerge throughout the disease period, the potential effects of sars-cov2 on the nervous system has attracted remarkable attention, and several possible mechanisms of neurological injury have been postulated (13). this virus can affect the central nervous system via olfactory nerves or, enter brain cells by binding to angiotensin-converting enzyme-2 (ace2) or cause neuroinflammation following a cytokine storm (3, 14). covid-19 can affect the central nervous system, peripheral nervous system, and musculoskeletal system, leading to various neurological manifestations including headache, anosmia, ageusia, dizziness, altered consciousness, myalgia, myelopathy, encephalopathy, meningitis, seizure, syncope, hemorrhage, and stroke (15, 16). despite the rapidly growing literature on this subject, correlations between neurological symptoms and/or neuroimaging findings in covid-19 and other variables are still mostly unknown. only a few studies have investigated the association between neurological symptoms and other variables. our objective in this study is to evaluate covid-19related neurological and neuroimaging findings in hospitalized patients, while investigating their relationship with various clinical, laboratory, and lung ct score characteristics. 2. methods 2.1. study design and setting this cross-sectional study was conducted between september 22, 2020 and march 30, 2021 at imam khomeini hospital complex and shohadaye tajrish medical center in tehran, iran. we used the strobe checklist as the reporting guideline for this study. this was a retrospective study and all admission, discharge, diagnostic, and therapeutic decisions were made based on the latest version of the national covid-19 protocol during the study, and we did not interfere with the patient’s diagnostic process and didn’t charge the patient or the system anything. the study protocol was approved by the ethics committee of aja university of medical sciences, receiving the ethics code number (ir.ajaums.rec.1399.163). 2.2. study population all adult (≥18 years old) hospitalized covid-19 patients with positive real-time reverse transcription-polymerase chain reaction (rt -pcr) test and a neuroimaging study (including brain and/or spine imaging) following the emergence of any acute neurologic manifestation during hospital stay were included in the study. exclusion criteria were: (a) known history of previous neurological disorders; (b) previous neuroimaging abnormalities; (c) neurologic manifestation with non-covid-19 etiology; and (d) incomplete medical records, which failed to meet the requirements for our checklist. acute neurologic manifestations included: headache, dizziness, altered consciousness, seizure, any focal neurologic symptoms, delirium, psychosis, and any other type of neuropathy. 2.3. outcomes and measurements a checklist was designed and developed to extract patients’ data. the collected data included demographic characteristics (age, gender, and underlying disease), clinical features (degree of severity on admission (measured using american thoracic society guidelines for community-acquired pneumonia (17), severe or non-severe), outcome (death or discharge), neurologic/psychiatric manifestations, and indication for neuroimaging), initial laboratory data (included a complete blood cell count (cbc), and assessment of renal function, c reactive protein (crp), erythrocyte sedimentation rate (esr), creatine kinase (ck), and lactate dehydrogenase (ldh) according to the clinical care needs of the patient), chest ct scan, and neuroimaging findings. all neurological symptoms in this study were evaluated by an expert neurologist after suspicion of a clinician during daily routine practice in the mentioned centres. neurologic manthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e10 figure 1: (a, b, c) acute infarct in posterior cerebral artery (pca) territory with restriction on diffusion-weighted magnetic resonance imaging (dwi) in a 53-year-old female with covid-19 on the ninth day of admission; (d) hyper dense materials in brain sulci more prominent on left peritoneal lobe in favor of subarachnoid hemorrhage (sah). figure 2: (a, b) large hyper dense heterogeneous lesion in right temporal lobe with peripheral edema, more evaluated with brain magnetic resonance imaging/venography (mri/mrv ), which showed abnormal signal in right sigmoid sinus compatible with cerebral venous thrombosis; (c) t2 flair images in a 39-year-old female with covid-19 shows some hyper intense predominantly subcortical and deep white matter lesions without periventricular and corpus callosum involvement suggestive of acute disseminated encephalomyelitis (adem). ifestations were divided into three groups: central nervous system (cns) manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system (pns) manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and acute psychiatric manifestations (psychosis and delirium). both neurological and psychiatric symptoms were extracted from the consultation notes of experienced neurologists and psychiatrists. acute cerebrovascular disorders including ischemic or hemorrhagic insults were diagnosed by clinical symptoms and brain imaging. seizure was diagnosed based on clinical symptoms at the time of presentation. indications for neuroimaging were also extracted from medical records and were categorized into six groups: 1) focal neurologic signs (including stroke, transient ischemic attack (tia) and all possible forms); 2) altered consciousness / reduced gcs; 3) delirium; 4) headache; 5) seizure; and 6) miscellaneous. 2.4. image acquisition and interpretation we obtained all the images in our study as per standard of care protocols. 1.5-t scanners (siemens avanto, germany) with standardized protocols were utilized for brain and spine magnetic resonance imaging (mri) scans. all ct and mri images were initially reviewed by two experienced neuroradiologists (each having at least ten years of neuroradiology experience), and any disagreements were settled by consensus. all available chest ct scans were evaluated for ct lung severity score via lobar based assessment (18). each of the five lung lobes was subjectively graded from 0 to 5 (0, no involvement; 1, involvement<5%; 2, involvement 6–25%; 3, involvement 26–50%; 4, involvement 51–75%; 5, involvement>75%) in lobar based evaluation. the total score was the sum of the individual lobar scores and ranged from 0 to 25. all neuroimaging was analysed for the following characteristics: 1) ischemic insults; 2) haemorrhagic insults; 3) leptomeningeal or cranial nerves enhancement; 4) cerebral venous thromthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zare dehnavi et al. 4 figure 3: distribution of neuroimaging findings based on neuroimaging indications. cvt: cerebral venous thrombosis. bosis; 5) acute encephalopathy; 6) white matter involvement and any other new abnormal findings. 2.5. statistical analysis all statistical analyses were conducted using spss version 20. mean and standard deviation were used for reporting normally distributed quantitative variables; median and interquartile range (iqr) were used for reporting quantitative variables that were not normally distributed, and frequency (percentage) was used to report categorical variables. independent sample t-test or mann whitney test was used for comparing two quantitative groups based on the result of shapiro-wilks for normality. chi square test, and if needed fisher’s exact test was used to evaluate the association between two categorical variables. we also performed multivariate binary logistic regression analysis on factors that significantly correlated with neuroimaging abnormality. pvalues < 0.05 were considered statistically significant. 3. results 3.1. demographic, clinical and laboratory characteristics during the study period, a total of 4372 hospitalized patients with sars-cov-2 infection were identified. of these, 211 patients met our inclusion criteria (52.6% male). their mean age was 60.7 (standard deviation (sd) =15.8) years (age range, 18-94 years). based on american thoracic society guidelines for community-acquired pneumonia, 75 (35.5%) of cases were categorized as severe covid-19 infections and 136 (64.5%) of them were non-severe. patients’ characteristics are presented in table 1. 84.4%, 19.4%, and 35.1% of the patients showed at least one cns, pns, and neuropsychiatric manifestation, respectively. cns findings were the most prevalent neurologic symptoms overall, with a significantly higher prevalence in the severe group (93.3% vs. 80.1%, p = 0.011). the most frequently recorded cns manifestations were: headache (40.3%), reduced consciousness (36%), and focal neurologic symptoms (18%). altered consciousness, focal neurologic findings, and seizures were more prevalent in severe infections compared to non-severe infections; headache was significantly higher in non-severe infections (29.3% vs. 46.3%, p = 0.016). neuropsychiatric manifestations were also fairly common, with a total prevalence of around 35%, and were significantly associated with infection severity (severe (44.0%) vs. non-severe (30.1%), p = 0.044). pns manifestations were the least common among these three categories, with an overall prevalence of about 20% and no remarkable difference between severe and nonsevere groups. in the pns group, 2 cases were also diagnosed with guillain-barre syndrome. clinical manifestations of patients are detailed in table 1. in the comparison of various factors between severe and non-severe cases, patients with severe infection were significantly older (64.5±14.2 vs. 58.6±16.4, p = 0.010), and had a higher mortality rate (p <0.001). in addition, past medical history of hypertension (54.7% vs. 39.7%, p = 0.037) also associated with severity. however, no other difference was observed between these two groups. regarding laboratory tests, patients with a severe infection had a higher inflammatory response, including higher neutrophil counts, lower lymphocyte counts, increased c-reactive protein levels, elevated erythrocyte sedimentation rate, and higher lactate dehydrogenase levels (p ≤ 0.010) compared to those with non-severe infection. during the study, 13 patients underwent lumbar this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e10 table 1: clinical and laboratory findings of patients based on severity of infection characteristics total (n= 211) severity of infection p severe n=75 non-severe n=136 age (year) 60.7±15.8 64.5±14.2 58.6±16.4 0.010 neuroimaging abnormality 63(29.9) 39(52) 24(17.6) <0.001 gender male 111(52.6) 39 (52) 72(52.9) 0.896 female 100 (47.4) 36 (48) 64(47.1) comorbidities hypertension 95(45) 41(54.7) 54(39.7) 0.037 diabetes mellitus 81(38.4) 26(34.7) 55(40.4) 0.409 heart disease 51(24.2) 17(22.7) 34(25.0) 0.705 copd 10(4.7) 4(5.3) 6(4.4) 0.763 ckd 14(6.6) 8(10.7) 6(4.4) 0.081 liver disease 7(3.3) 3(4.0) 4(2.9) 0.681 malignancy 18(8.5) 8(10.7) 10(7.4) 0.409 tobacco smoking 26(12.3) 9(12.2) 17(12.5) 0.916 outcome discharged 158(74.9) 38(50.7) 120(88.2) <0.001 expired 53(25.1) 37(49.3) 16(11.8) cns total 179(84.4) 70(93.3) 109(80.1) 0.011 dizziness 33(15.7) 15(20) 18(13.2) 0.195 headache 85(40.3) 22(29.3) 63(46.3) 0.016 loc 76(36.0) 46(61.3) 30(22.1) <0.001 ataxia 22(10.4) 9(12.0) 13(9.6) 0.579 seizure 11(5.2) 9(12.0) 2(1.5) 0.001 focal neurologic findings 38(18.0) 23(30.7) 15(11.0) <0.001 encephalopathy 4(1.9) 3(4.0) 1(0.7) 0.096 pns taste impairment 23(10.9) 3(4.0) 20(14.7) 0.017 smell impairment 24(11.4) 3(4.0) 21(15.4) 0.012 visual impairment 10(4.7) 5(6.7) 5(3.7) 0.328 guillain-barre syndrome 2(0.9) 1(1.3) 1(0.7) 0.668 psychiatric total 74(35.1) 33(44.0) 41(30.1) 0.044 laboratory wbc (cells /µl) 10219±4932 10930±6344 9827±3917 0.174 neutrophil (cells /µl) 7904±4353 9271±5569 7150±3295 0.003 lymphocyte (cells /µl) 1586±963 933±643 1945±921 <0.001 platelet (cells /µl) 235004±114506 212413±102995 247463±118935 0.033 esr (mm/hr) 43.0±33.1 62.1±26.9 32.4±31.4 <0.001 c-reactive protein (mg/l) 37.4±29.0 55.4±23.9 28.0±27.3 <0.001 cpk (u/l) 151.1±345.9 192.8±183.7 128.6±406.3 0.001 lactate dehydrogenase (u/l) 543.2±436.9 661.3±585.4 478.7±313.7 0.01 blood urea nitrogen (mg/dl) 56.3±49.2 70.8±53.1 48.3±45.2 0.002 creatinine (mg/dl) 1.5±1.0 1.6±1.1 1.3±0.9 0.075 csf high wbc (cells/mm3 ) 4/13 ——increased protein (mg/dl) 5/13 ——data presented as mean ± standard deviation (sd) or number (%). esr: erythrocyte sedimentation rate; loc: loss of consciousness; cpk: creatine phosphor kinase; wbc: white blood cell; ckd: chronic kidney disease; copd: chronic obstructive pulmonary disease. puncture and their cerebrospinal fluid findings are shown in table 1. 3.2. neuroimaging findings in the study population, 160 (75.8%) were examined using brain ct, 5 (2.4%) underwent brain and/or spine mri, and 46 (21.8%) underwent both ct and mri. apart from changes commonly found in elderly patients, neuroimaging indicated no major abnormalities in 148 (70.1%) participants. abnormal findings were seen in 63 (29.9%) cases, with the rate of abnormality being significantly higher in patients with severe covid-19 infection (52 % (severe) vs. 17.6% (non-severe), p < 0.001). the main neurologic imaging hallmark was acute ischemic infarcts, found in 38 (18%) of the 211 individuals. of these, 35 (92%) had territorial infarction and 3 (8%) had non-territorial infarcts. ischemia in the territory supplied by the middle cerebral artery (mca) (27/35, 77%) was the most prevalent among territorial infarcts. the rest included: 3 posterior cerebral artery (pca), 1 anterior cerebral artery (aca), 2 inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zare dehnavi et al. 6 table 2: summary of patients’ neuroimaging (computed tomography scan or magnetic resonance imaging) findings variables values n (%) indication for neuroimaging headache 57 (27.0) altered consciousness 54 (25.6) focal neurologic signs 42 (19.9) delirium 38 (18.0) seizure 11 (5.2) miscellaneous 9 (4.3) ischemic insult territorial 35 (16.6) non-territorial 3 (1.4) hemorrhagic insult large intracranial and intraventricular 5 (2.4) microhemorrhage 8 (3.8) subarachnoid hemorrhage (sah) 3(1.4) territory of ischemic insult middle cerebellar artery (mca) 27(12.8) posterior cerebellar artery (pca) 5(2.4) anterior cerebellar artery (aca) 2(0.9) infratentorial 3(1.4) other findings acute encephalopathy 2 (0.9) leptomeningeal enhancement 1 (0.5) pituitary apoplexy 1(0.5) cranial nerves 0 (0.00) cerebral venous thrombosis (cvt) 7 (3.3) transverse myelitis 1 (0.5) demyelination (white matter involvement) 1 (0.5) fratentorial, 1 pca+aca, and 1 pca +infratentorial (figure 1). intracranial hemorrhages (ichs) were the second most common finding (16/211), with micro-hemorrhages being the most common (8/16, 50%), followed by 5 large cranial hemorrhages and 3 cases of subarachnoid hemorrhage (sah) (figure 1). of these, one was a 27-year-old female with no remarkable past medical history surveyed with complaints of severe headache and altered mental status approximately one week after the beginning of covid-19 symptoms who underwent brain ct and mri. cranial imaging revealed brain edema and a 12×9×8mm mass in the left aspect of the pituitary fossa with a hemorrhagic appearance suggestive of pituitary adenoma apoplexy. seven cases were diagnosed with cerebral venous thrombosis (cvt), one of which had superior sagittal sinus thrombosis accompanied by leptomeningeal enhancement. another case was a 66-year-old man with hypertension, classified as a severe infection, who underwent cranial imaging due to decreased consciousness and seizure. his brain mri showed an abnormal signal area with hemorrhagic change in the right temporal lobe and an abnormal signal in the right sigmoid sinus favoring venous infarct due to dural venous sinus thrombosis. in mrv (magnetic resonance venography), transverse and sigmoid sinus was not seen, and abnormal signals in t2/w sequences consistent with venous thrombosis were present (figure2). details of neuroimaging characteristics are summarized in table 2. 3.3. neuroimaging indications among reasons for undergoing imaging, the most common indications were headache (27%), impaired mental status (25.6%), and focal neurologic signs (19.9%) (table2). indications for neuroimaging matched with neuroimaging characteristics are presented in figure 3. most of the patients with headache (52/57, 91%) and delirium (32/38, 84%) had no abnormal findings on neuroimaging, but most of those who had seizures (7/11, 64%) had pathologic findings on neuroimaging. most ischemic or hemorrhagic insults were seen among patients who underwent neuroimaging due to altered consciousness or focal neurology (42/55, 76%). on the other hand, all cvt cases were detected in people who had headaches and/or seizures. 3.4. association of neuroimaging with clinical, laboratory features, and lung ct score table 3 presents the characteristics of patients with and without neuroimaging abnormalities. we found that individuals with abnormal findings in neuroimaging studies were significantly older (p = 0.009) and had a higher level of esr, crp, and neutrophil count (p ≤ 0.018). the analysis also revealed that chest ct score of patients with covid-19 who had new abnormalities on neuroimaging was significantly higher than those who didn’t have any pathologic neuroimaging findings (mean ct score±sd, 11.1±4.8 vs. 5.9±4.8, p < 0.001). however, no other related factor was detected. 3.5. predictors of neuroimaging abnormality the multivariate logistic regression on the factors influencing neuroimaging abnormality is presented in table 4. this analysis showed that age (b=0.041, se=0.013, exp(b)=1.042, p = 0.002), neutrophil count (b=0.000, se=0.000, exp(b)=1, p = 0.039) and lung ct score (b=-0.181, se=0.045, exp(b)=0.834, p = 0.000) were strong predictors of neuroimaging abnormality. however, esr, crp, and lymphocyte count showed no significant prediction ability for neuroimaging abnormality (p ≥ 0.116). 4. discussion in this study, we surveyed hospitalized patients with covid19-related neurologic symptoms requiring neuroimaging, focusing on their clinical, laboratory, and chest ct scan characteristics. our patients had a wide range of neurologic symptoms as well as neuroimaging indications and findings. we this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e10 table 3: comparing the patients’ characteristics between cases with and without acute neuroimaging abnormality characteristics total (n= 211) neuroimaging abnormality p with n=63 without n=148 age (years) mean ± sd 60.7 ± 15.8 56.3 ± 16.1 62.6 ± 15.4 0.009 gender male 111 (52.6) 28 (44.4) 83 (56.1) 0.121 female 100 (47.4) 35 (55.6) 65 (43.9) comorbidities hypertension 95 (45.0) 30 (47.6) 65 (43.9) 0.621 diabetes 81 (38.4) 22 (34.9) 59 (39.9) 0.499 heart disease 51 (24.2) 13 (20.6) 38 (25.7) 0.434 copd 10 (4.7) 1 (1.6) 9 (6.1) 0.160 chronic kidney disease 14 (6.6) 6 (9.5) 8 (5.4) 0.271 liver disease 7 (3.3) 0 (0.00) 7 (4.6) 0.079 malignancy 18 (8.5) 4 (6.3) 14 (9.5) 0.459 tobacco smoking 26 (12.3) 10 (15.9) 16 (10.8) 0.306 outcome discharged 158 (74.9) 42 (66.7) 116 (78.4) 0.073 expired 53 (25.1) 21 (33.3) 32 (21.6) laboratory findings wbc (cells/µl) 10219±4932 11090±5806 9849±4480 0.094 neutrophil (cells /µl) 7904 ± 4353 9158 ± 5094 7371 ± 3894 0.006 lymphocyte (cells /µl) 1586 ± 963 1238 ± 714 1733 ± 1017 <0.001 platelet (cells /µl) 235004±114506 247349±105979 229750±117901 0.308 esr (mm/hr) 43.0 ± 33.1 52.7 ± 27.5 39.0 ± 34.3 <0.001 crp (mg/l) 37.4 ± 29.0 44.3±26.3 34.4 ± 29.7 0.018 cpk (u/l) 151.1 ± 345.9 214.7±592.2 121.5 ± 107.3 0.235 ldh (u/l) 543.2 ± 436.9 518.1±358.0 554.0 ± 467.5 0.632 bun (mg/dl) 56.3 ± 49.2 50.0±37.3 59.0 ± 53.4 0.166 creatinine (mg/dl) 1.5 ± 1.0 1.2 ± 0.6 1.5 ± 1.1 0.027 ct lung severity score (0-25) mean ± sd 7.4 ± 5.3 11.1 ± 4.8 5.9 ± 4.8 <0.001 data presented as mean ± standard deviation (sd) or number (%). wbc: white blood cell; ct: computed tomography scan; esr: erythrocyte sedimentation rate; crp: c-reactive protein; cpk: creatine phosphokinase; ldh: lactate dehydrogenase; bun: blood urea nitrogen; copd: chronic obstructive pulmonary disease. table 4: the multivariate binary logistic regression of the potential factors predicting neuroimaging abnormality parameters b standard error exp (b) p value constant -0.175 0.954 0.839 0.854 age 0.041 0.013 1.042 0.002 neutrophil 0.000 0.000 1.000 0.039 lymphocyte 0.000 0.000 1.000 0.116 erythrocyte sedimentation rate (esr) -0.006 0.009 0.994 0.486 c reactive protein (crp) 0.004 0.010 1.004 0.685 creatinine 0.369 0.318 1.446 0.246 ct lung severity score -0.181 0.045 0.834 0.000 ct: computed tomography. discovered that nearly 30% of covid-19 patients with neurological involvement had an abnormality in their neuroimaging, with the most commonly reported abnormality being acute ischemic infarcts, followed by ich. analysis showed that the emergence of acute neuroimaging findings was related to a higher lung ct severity score as well as age, neutrophil count, lymphocyte count, esr, and crp level. multivariate logistic regression on the factors influencing neuthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zare dehnavi et al. 8 roimaging abnormality identified age, neutrophil count, and lung ct score as strong predictors of new abnormal neuroimaging findings. we also found that being old; having a past medical history of htn, having a cns manifestation, and having neuropsychiatric symptoms are associated with disease severity. patients with hypertension in our study were more likely to have severe covid-19 infection; similar to the findings of several previous papers (19-22) which found that hypertension is related to a greater risk of mortality. so, this underlying condition should be considered by clinicians as a predictor of progression of covid-19 to severe status and poor outcome. patients with severe infection were found to be older. according to some studies (19, 21, 22), older patients had a greater mortality rate. patients with abnormal neuroimaging were also found to be older, which is consistent with the findings of chen et al., who reported that age is associated with acute cerebrovascular events in covid-19 patients (20). this is important because in elderly patients with covid-19, who have nonspecific symptoms of neurological involvement, the likelihood of neurological involvement should always be considered, and the threshold for neurological imaging should be lower. however, in contrast to some investigations that found a higher prevalence of severe cases in men, no gender difference was observed between these two groups in our study (23-25). cns manifestations were shown to be the most prevalent neurological manifestation, with headache being the most common (40.3%). this finding is in agreement with previous studies, which found headache to be one of the most common neurological manifestations, with a frequency ranging from 4 to more than 40% (6, 7, 16, 19, 21, 22, 26). we found that almost 30% of covid-19 patients with neurologic manifestations had abnormal neuroimaging. this number has been observed to range from 20% to more than 80% in different studies (26-32). the disparities could be due to the lower threshold for undergoing brain imaging in iran’s health system setting, sample-size differences, or differences in the characteristics of the sample groups. for example, in the study that reported this number to be above 80%, a greater percentage of the sample experienced more serious neurological symptoms, such as paresis or loss of consciousness, or had more comorbidities. like mahammedi et al.(32), we observed that patients who had acute abnormalities on neuroimaging had a significantly higher ct lung severity score. although further research is needed to verify this association, it suggests that any neurological symptoms in covid19 patients with a high ct lung severity score should be taken seriously. in addition, we can employ the ct lung severity score as a prognostic tool in managing covid-19 patients with neurological manifestations. ischemia and infarction were the most common imaging abnormalities, as they had been in many earlier studies (19, 28, 30, 33, 34). however, we have an inadequate understanding of the mechanisms of the neurologic manifestations presented in covid-19 patients, and we don’t know whether they were caused by direct invasion of the coronavirus to the central nervous system (35). sars-cov-2 has been demonstrated to enhance coagulopathy in previous investigations (36, 37), thus finding ischemia and infarction in neuroimaging appears to be a possibility that should be considered. we also reported four cases of encephalopathy, two of which displayed encephalopathy features on brain imaging. both were in the severe group and had to undergo neuroimaging due to delirium and focal neurologic signs; tragically, one of them passed away during the hospital stay. we also described a case of pituitary apoplexy in a young woman, which has been recorded in only a few cases in the covid-19 setting (38). there are some limitations to this study that should be highlighted. even though our sample was large and multi-center, we only investigated hospitalized patients in two large hospitals. our study was retrospective, which can contribute to an underestimation of variable frequency. multinational and outpatient studies on long-term outcomes as well as other study designs should be considered. due to the subjective nature of neuroimaging and chest ct scan findings, it was challenging to standardize them. we overcame this constraint by having two expert neuroradiologists review all ct and mri images and reaching a consensus on any disputes. another major limitation was that we only enrolled covid19 patients with neurologic manifestations who underwent neuroimaging. because performing neuroimaging on all patients as a routine is unnecessary and immoral, increasing the probability of exposure to the virus during a pandemic, imaging was done selectively in patients with more serious and significant neurologic symptoms. 5. conclusion our study demonstrates that roughly 30% of the studied cases had various new neuroimaging abnormalities, which should not be dismissed during the covid-19 pandemic. furthermore, age, neutrophil count, and lung ct score were shown to be strong predictors for the emergence of neuroimaging pathologic findings. 6. declarations 6.1. acknowledgments we thank all the medical team at the neurology, radiology, infectious disease, and emergency medicine departments of both hospitals, including doctors, nurses, the health care experts, and the staff. we also thank the patients and their families for their cooperation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e10 6.2. authors’ contributions design of the study by az, ms, a.r and f.a; data acquisition by az, ma, mr and a.t; images review by hh, na, and ma, data analysis and interpretation by mha; ar, fa, and rh; drafting the manuscript by az, mha, hs, and ab; revision of the manuscript by ms, ar, fa, ma, and at; the final version of the manuscript is approved by all the authors. 6.3. funding and supports none. 6.4. conflict of interest the authors declare no conflict of interest 6.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. references 1. team ee. note from the editors: world health organization declares novel coronavirus (2019-ncov ) sixth public health emergency of international concern. eurosurveillance. 2020;25(5):200131e. 2. world health organization. iran (islamic republic of ): who coronavirus 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10.1007/s11102-020-01080-w this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem emergency. 2017; 5 (1): e54 or i g i n a l re s e a rc h nerve stimulator versus ultrasound-guided femoral nerve block; a randomized clinical trial arash forouzan1, kambiz masoumi1∗, hassan motamed1, seyed mohammad reza gousheh2, akram rohani1 1. department of emergency medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. department of anesthesiology, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: december 2016; accepted: january 2017; published online: 18 january 2017 abstract: introduction: pain control is the most important issue in emergency department management of patients with femoral bone fractures. the present study aimed to compare the procedural features of ultrasonography and nerve stimulator guided femoral nerve block in this regard. methods: in this randomized clinical trial, patients with proximal femoral fractures presenting to emergency department were randomly divided into two groups of ultrasonography or nerve stimulator guided femoral block and compared regarding success rate, procedural time, block time, and need for rescue doses of morphine sulfate, using spss 20. results: 50 patients were randomly divided into two groups of 25 (60% male). the mean age of studied patients was 35.14 ± 12.95 years (19 – 69). the two groups were similar regarding age (p= 0.788), sex (p = 0.564), and initial pain severity (p = 0.513). in 2 cases of nerve stimulator guided block, loss of pinprick sensation did not happen within 30 minutes of injection (success rate: 92%; p = 0.490). ultrasonography guided nerve block cases had significantly lower procedural time (8.06 ± 1.92 vs 13.60 ± 4.56 minutes; p < 0.001) and lower need for rescue doses of opioid (2.68 ± 0.74 vs 5.28 ± 1.88 minutes; p < 0.001). conclusion: ultrasonography and nerve stimulator guided femoral block had the same success rate and block duration. however, the ultrasonography guided group had lower procedure time and lower need for rescue doses of morphine sulfate. therefore, ultrasonography guided femoral block could be considered as an available, safe, rapid, and efficient method for pain management of femoral fracture in emergency department. keywords: femoral fractures; ultrasonography, interventional; transcutaneous electric nerve stimulation; pain management; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: forouzan a, masoumi k, motamed h, gousheh sm, rohani a. nerve stimulator versus ultrasound-guided femoral nerve block; a randomized clinical trial. emergency. 2017; 5(1): e54. 1. introduction f emoral bone fractures are not infrequent and are usually associated with severe pain (1, 2). pain control is the most important issue in emergency department management of these patients. different methods of pain management such as administration of intravenous opioids, tranquilizers and muscle relaxants, and even inhaled drugs are introduced for this propose (3, 4). however, allergic reactions, airway compromise, respiratory depression, and hy∗corresponding author: kambiz masoumi; emergency department, imam khomeini general hospital, azadegan, ahvaz jundishapur university of medical sciences ahvaz, iran. postal code: 6193673166 tel: 0098 613 2222085; cellphone: 0098 911 343 9637; fax: 0098 613 2225763 email: emdajums@yahoo.com potension are among the most important complications of the mentioned methods. regional nerve blocks have shown benefits over the procedural sedation and analgesia (psa) for pain management in emergency settings (5-8). regional anesthesia without any important adverse effects on central nervous system or systemic circulation, could be helpful in managing pain and decreasing the volume of narcotic and opioid usage (1, 9). anatomic landmarks guided femoral nerve block is an effective method for reducing pain in adults and children referring to emergency departments with femoral fractures (6). however, injection of drug in the femoral artery is the most undesirable complication of this method. nowadays, nerve stimulator and ultrasonography guided methods of block have increased the safety level of the procedure (5, 10). ultrasonography allows physicians to observe the nerves directly so that the needle can this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. forouzan et al. 2 be kept away from sensitive organs and distribution of regional anesthetic can be monitored. also, using transcutaneous electric nerve stimulation could be helpful in localizing the nerve and increasing the effectiveness of block (11, 12). however, emergency physicians are more familiar with ultrasonography than nerve stimulator, and ultrasonography as a noninvasive tool is more available in emergency departments. based on the above mentioned points, the present study aimed to compare the characteristics of ultrasonography and nerve stimulator guided femoral nerve block in pain management of femoral fractures in emergency department. 2. methods 2.1. study design and setting this randomized clinical trial was conducted on patients with proximal femoral fractures (including neck, intertrochanteric, and proximal shaft fractures), admitted to emergency departments of imam khomeini hospital, ahvaz, iran, from january to december 2015, aiming to compare the procedure features of nerve stimulator and ultrasonography guided femoral nerve block techniques. the protocol of the study was approved by ethical committee of ahvaz jundishapur university of medical sciences and registered in iranian registry of clinical trials under number irct2015030221289n1. researchers adhered to all principles of helsinki declaration and confidentiality of patients’ information during the study period. informed consent was obtained from the study subjects before enrollment. 2.2. participants patients with proximal femoral fractures, aged 18-80 years, referred to emergency department were included. the exclusion criteria were hemodynamic instability, loss of consciousness, contraindications of receiving regional anesthesia or opioid administration (hypersensitivity to any variety of regional anesthetics such as amide and other compounds, systemic or local infections, abnormal neurological examination, and risk of compartment syndrome), opioid addiction, severe pulmonary or heart disease, diabetes, and coagulopathy. 2.3. intervention eligible patients were randomly divided into two groups of nerve stimulator or ultrasonography guided femoral nerve block, using simple random sampling technique. all patients received 0.1 mg per kg intravenous morphine sulfate before initiation of procedure. a single dose of 10 ml of lidocaine1% was used for regional anesthesia. nerve stimulation was done by a 50 gauge needle (with 20 degrees tip angle) using a pajunk multistim sensor device. the needle was inserted with a 45 degrees angle just inferior and lateral to where the femoral artery crosses the inguinal ligament. at first, the flow rate of device was set at 2.5 mv, and then after an appropriate response from the muscle (quadriceps muscle contraction), the flow rate was reduced to 0.4 mv so that the muscle response could still be visible. ultrasonography guided nerve blocks were done using a high frequency (7 – 12 mhz) linear array probe (the sonoace-x8 ultrasound system -samsung medison co., ltd., south korea) in a supine position with totally abducted legs (figure 1 and 2). all patients were under continuous cardiac, pulse rate, respiratory rate, blood pressure, and o2 saturation monitoring during the procedure. pain severity was measured using visual analogue scale (vas). considering 30 minutes duration for loss of pinprick sensation (13), in cases with ≥ 3 pain score, 30 minutes after block, additional rescue doses of morphine sulfate (0.1 mg/kg) were administered. the sensory (pinprick sensation) and motor response were measured every 5 minutes during 30 minutes after the injection of lidocaine. leg extension against gravity and passive hip flexion in 45o were measured for motor nerve block examination. procedures were done by a trained senior emergency medicine resident under supervision of an emergency medicine specialist. operators were trained regarding ultrasonography and nerve stimulator guided nerve block during an 8 hour educational course and by doing the procedure under supervision of an expert radiologist. 2.4. data gathering a predesigned checklist consisting of demographic data (age, sex), initial pain severity, procedure time, block duration, success rate, and need for rescue doses of morphine sulfate was used for data gathering. procedure time was defined as interval between lidocaine injection and loss of pinprick sensation. also, interval between loss and recovery of pinprick sensation was considered as block duration. a successful block was defined as complete sensory loss in the femoral nerve distribution by 30 minutes. data gathering was done by a blinded observer. 2.5. statistical analysis considering 1.2 and 0.4 mg rescue doses of morphine sulfate in the two groups (14), 95% confidence interval, and the power of 80%, the number of samples per arm was estimated to be 25 cases. analysis was done using spss 20. data were reported as mean and standard deviation or frequency and percentage. t test was used to compare means and chi square or fisher’s exact test for comparing the categorical variables. p-value <0.05 was considered as significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e54 figure 1: ultrasonography view of right inguinal structures. figure 2: position of ultrasonography probe in inguinal area. 3. results 50 patients with proximal femur fracture were randomly divided into two groups of 25 (60% male). the mean age of studied patients was 35.14 ± 12.95 years (19 – 69). table 1 compares the baseline characteristics of studied patients. two groups had the same condition regarding age (p= 0.788), sex (p = 0.564), and initial pain severity (p = 0.513). loss of pinprick sensation within 30 minutes of injection did not happen in 2 cases of nerve stimulator guided block (success rate: 92%). the success rate, mean procedure time, block time, and amount of rescue doses of morphine sulfate, which were used, were compared between two groups in table 2. ultrasonography guided nerve block cases had significantly lower procedural time (p < 0.001) and lower need for rescue doses of opioid (p < 0.001). 4. discussion based on the main findings of the present trial, ultrasonography and nerve stimulator guided femoral block had the same success rate and block duration. however, the ultrasonography guided group had lower procedure time and lower need for rescue doses of morphine sulfate. kumar et al., comparing these two techniques for axillary brachial plexus block, also showed the similar success rate (95% versus 93.2; p = 0.35) of both groups (15). in another study by cataldo et al., the failure rates after 30 minutes in both groups were not significant (16). in consistency with our findings, tran et al. (17), demonstrated that the procedure time of superficial cervical plexus block was lower in the ultrasonography guided nerve block group (119 vs. 61 seconds, p<0.001). duration of procedure did not show any difference between the two methods. kumar et al., (15) showed that the duration of sensory axillary nerve blocks in the ultrasonography guided group was 6.33 minutes versus 6.17 minutes in the nerve stimulation group. durations of motor block in the ultrasound-guided group and the nerve stimulation group were 23.33 and 23.17 minutes, respectively. unlike our study, these differences were not statistically significant. a randomthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. forouzan et al. 4 table 1: comparison of baseline characteristics between studied groups variable ultrasonography nerve stimulator p value age (year) 35.64 ± 13.29 34.64 ± 12.86 0.788 sex male 16 (64) 14 (56) 0.564 female 9 (36) 11 (44) pain severity ( vas)* 8.88 ± 0.72 8.52 ± 2.63 0.513 *vas: visual analogue scale at the initiation of procedure. data were presented as mean ± standard deviation or frequency and percentage. table 2: comparison of success rate, procedure time, block duration, and amount of morphine sulfate rescue doses between two groups variable ultrasonography nerve stimulator p value success rate (30 minute) 25 (100) 23 (92) 0.490 procedure time (minute) 8.06 ± 1.92 13.60 ± 4.56 < 0.001 block duration (minute) 61.56 ± 16.50 57.64 ± 23.85 0.502 rescue dose (mg) 2.68 ± 0.74 5.28 ± 1.88 < 0.001 data were presented as mean ± standard deviation or frequency and percentage. ized clinical trial performed by perlas et al., comparing the success rate of the sciatic nerve block with ultrasonography and nerve stimulator techniques, showed that the duration of the procedure was similar in both groups (18). rubin et al., showed that duration of the procedure and the time of onset for nerve block in the ultrasound-guided group were significantly lower than the nerve stimulation group (19). in a meta-analysis by choi et al., reporting seven studies in which opioid consumption was reported, the reduction was mentioned in the ultrasound-guided method in three studies (20). in the three studies that evaluated the time of onset of analgesia, the ultrasonography guided approach was preferred. oberndorfe et al. (21) showed that the amount of drug administration for regional anesthesia in the ultrasonography guided group was less than the nerve stimulation group (p <0.001). in contrast, maalouf et al. showed that the mean amount of oral morphine equivalents used in ultrasonography and nerve stimulator guided groups were similar (22). it seems that using ultrasonography guided femoral nerve block could be considered as an available, safe, rapid, and efficient method for pain management of patients presenting to emergency department following femoral fracture. 5. limitation low sample size and not performing the study in a double blind manner are among the most important limitations of this study. however, data gathering by a blinded observer can decrease the bias. 6. conclusion based on the main findings of the present trial, ultrasonography and nerve stimulator guided femoral block had the same success rate and block duration. however, the ultrasonography guided group had lower procedure time and lower need for rescue doses of morphine sulfate. 7. appendix 7.1. acknowledgements: we gratefully acknowledge the dedicated efforts of the investigators, the coordinators, the volunteer patients who participated in this study, and the clinical research development unit (crdu) of the hospital. 7.2. author’s contribution: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding: this study was financially supported by ahvaz jundishapur university of medical sciences. 7.4. conflict of interest: the authors have indicated that they have no conflicts of interests regarding the content of this article. references 1. mutty ce, jensen ej, manka ma, anders mj, bone lb. femoral nerve block for diaphyseal and distal femoral fractures in the emergency department. j bone joint surg am. 2007;89(12):2599-603. 2. christos sc, chiampas g, offman r, rifenburg r. ultrasound-guided three-in-one nerve block for femur fractures. western journal of emergency medicine. 2010;11(4). 3. wathen je, gao d, merritt g, georgopoulos g, battan fk. a randomized controlled trial comparing a fasthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e54 cia iliaca compartment nerve block to a traditional systemic analgesic for femur fractures in a pediatric emergency department. annals of emergency medicine. 2007;50(2):162-71. e1. 4. parker mj, handoll hh, griffiths r. anaesthesia for hip fracture surgery in adults. the cochrane library. 2004. 5. wu jj, lollo l, grabinsky a. regional anesthesia in trauma medicine. anesthesiology research and practice. 2011;2011. 6. lippert sc, nagdev a, stone mb, herring a, norris r. pain control in disaster settings: a role for ultrasoundguided nerve blocks. annals of emergency medicine. 2013;61(6):690-6. 7. griffin j, nicholls b. ultrasound in regional anaesthesia. anaesthesia. 2010;65(s1):1-12. 8. hunter tb, peltier lf, lund pj. radiologic history exhibit: musculoskeletal eponyms: who are those guys? 1. radiographics. 2000;20(3):819-36. 9. casati a, baciarello m, di cianni s, danelli g, de marco g, leone s, et al. effects of ultrasound guidance on the minimum effective anaesthetic volume required to block the femoral nerve. british journal of anaesthesia. 2007;98(6):823-7. 10. mittal r, vermani e. femoral nerve blocks in fractures of femur: variation in the current uk practice and a review of the literature. emergency medicine journal. 2013:emermed-2012-201546. 11. alimohammadi h, shojaee m, samiei m, abyari s, vafaee a, mirkheshti a. nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial. emergency. 2013;1(1):4. 12. alimohammadi h, azizi m-r, safari s, amini a, kariman h, hatamabadi hr. axillary nerve block in comparison with intravenous midazolam/fentanyl for painless reduction of upper extremity fractures. acta medica iranica. 2014;52(2):122-4. 13. beaudoin fl, nagdev a, merchant rc, becker bm. ultrasound-guided femoral nerve blocks in elderly patients with hip fractures. the american journal of emergency medicine. 2010;28(1):76-81. 14. fletcher ak, rigby as, heyes fl. three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency department: a randomized, controlled trial. annals of emergency medicine. 2003;41(2):227-33. 15. kumar lca, sharma cd, sibi me, datta cb, gogoi lcb. comparison of peripheral nerve stimulator versus ultrasonography guided axillary block using multiple injection technique. indian journal of anaesthesia. 2014;58(6):700. 16. cataldo r, carassiti m, costa f, martuscelli m, benedetto m, cancilleri f, et al. starting with ultrasonography decreases popliteal block performance time in inexperienced hands: a prospective randomized study. bmc anesthesiology. 2012;12(1):1. 17. tran dq, dugani s, finlayson rj. a randomized comparison between ultrasound-guided and landmark-based superficial cervical plexus block. regional anesthesia and pain medicine. 2010;35(6):539-43. 18. perlas a, brull r, chan vw, mccartney cj, nuica a, abbas s. ultrasound guidance improves the success of sciatic nerve block at the popliteal fossa. regional anesthesia and pain medicine. 2008;33(3):259-65. 19. rubin k, sullivan d, sadhasivam s. are peripheral and neuraxial blocks with ultrasound guidance more effective and safe in children? pediatric anesthesia. 2009;19(2):92-6. 20. choi s, brull r. is ultrasound guidance advantageous for interventional pain management? a review of acute pain outcomes. anesthesia & analgesia. 2011;113(3):596-604. 21. oberndorfer u, marhofer p, bãűsenberg a, willschke h, felfernig m, weintraud m, et al. ultrasonographic guidance for sciatic and femoral nerve blocks in childrenâăă. british journal of anaesthesia. 2007;98(6):797-801. 22. maalouf d, liu ss, movahedi r, goytizolo e, memstoudis sg, yadeau jt, et al. nerve stimulator versus ultrasound guidance for placement of popliteal catheters for foot and ankle surgery. journal of clinical anesthesia. 2012;24(1):44-50. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e49 ca s e re p o rt prolonged fever; a case report of medical malpractice fares najari1∗, nasser malekpour-alamdari2, ideh baradaran kial3, dorsa najari4, sahar mirzaei5 1. department of forensic medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of general surgery, shahid beheshti university of medical sciences, tehran, iran. 3. karaj forensic medicine organization, karaj, iran. 4. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 5. school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. received: april 2021; accepted: may 2021; published online: 3 july 2021 abstract: any surgical or preoperative treatment and diagnostic procedure may be associated with complications and risks. therefore, introduction of complicated cases plays an important role in educating those involved in the diagnosis of patients. generally, if a physician or a nurse is informed that an item is inadvertently left behind in a patient’s body during surgery, he/she is obliged to take action by notifying the healthcare system authorities and informing the patient as soon as possible; otherwise, he/she has committed a disciplinary violation. here we present a 27-year-old female patient with a history of renal failure with prolonged fever following a retained shaldon catheter in a patient’s chest. keywords: catheters; catheterization, central venous; malpractice; renal dialysis; foreign bodies; fever cite this article as: najari f, malekpour-alamdari n, baradaran kial i, najari d, mirzaei s. prolonged fever; a case report of medical malpractice. arch acad emerg med. 2021; 9(1): e48. https://doi.org/10.22037/aaem.v9i1.1217. 1. introduction many critically ill patients require invasive medical procedures annually; one of which is intravenous catheterization, with a complication frequency of 15%, as reported in previous studies (1). central venous catheterization is an important part of care in the intensive care units (icus), emergency wards, and operating rooms (2). it is widely used to administer antibiotics and chemotherapy drugs, provide parenteral nutrition and high-flow access for hemodialysis or plasmapheresis, and monitor the central venous pressure. central venous catheterization is also associated with emergency complications, such as bleeding from the catheter site, pneumothorax, hemothorax, ruptured artery, catheter dislocation and displacement, and embolism (3). however, a limited number of cases of retained iatrogenic catheters as foreign bodies have been reported so far (4). also, few cases of retained hemodialysis catheters have been reported. here we present a 27-year-old female patient with a history of re∗corresponding author: fares najari; department of forensic medicine, shohada-ye-tajrish hospital, tajrish square, shahrdari st.,tehran, iran. email: najari.hospital@sbmu.ac.ir, tel: 00989123195140, orcid: 0000-0003-06450566. nal failure with prolonged fever following a retained shaldon catheter in a patient’s chest. 2. case presentation a 27-year-old female patient (height: 170 cm; weight: 60 kg) was referred to our internal medicine clinic with complaints of fever, weakness, lethargy, and anorexia. she had developed fever ten months before attending the clinic, mostly in the evening or at night. she reported gradual, but progressive weakness, lethargy, and anorexia, with a 7-kg weight loss in the past month. she had undergone hemodialysis in another center over the past ten months (three times a week) due to advanced renal failure. she had also been diagnosed with hyperlipidemia and hypertension about ten years ago, which were controlled with losartan (50 mg twice a day) and lasix (40 mg daily). she also had a history of suspected pyelonephritis before the age of five, but could not remember the treatment details. the hemodialysis procedure had been initiated with the implantation of a shaldon catheter into the right jugular vein; however, due to the catheter dysfunction, a permacath was inserted at the same site, as reported by the patient. she had been hospitalized three times due to acute infection during the ten months of hemodialysis at the same center. she was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. najari et al. 2 treated with antibiotics and was discharged with good general health despite experiencing the side effects of medications. in the fourth hospitalization period, she also developed asthma after antibiotic therapy and was admitted to the internal department of another center for further examinations due to the lack of recovery and prolonged fever. the patient appeared ill, emaciated, and impatient in the examination, and her vital signs were as follows: blood pressure (bp): 130/85 mmhg; pulse rate (pr): 94/min; respiratory rate (rr): 24/min; t: 37.8◦c; oxygen saturation (o2sat): 93%; and blood sugar (bs): 99 mg/dl. no abnormalities were found in the head, face, or neck examination (except for an old scar of permacath placement). a 2/6 murmur was heard at the right sternal border. the lungs and the internal organs were normal in abdominal examination. the results of the laboratory tests showed hypochromic microcytic anemia, high calcitonin, leukocytosis with high neutrophil count, and high erythrocyte sedimentation rate (esr) (table 1). thyroid function test and urine analysis were normal. the result of triple blood and urine culture was negative. the patient was re-examined with a possible diagnosis of subacute endocarditis. in further examinations, chest and lateral chest radiographs upon admission showed a permacath in the posterior vena cava, with the tip positioned in the right atrium and a catheter placed parallel to the right atrium and the right ventricle with an unknown origin, without proximal connection to the implanted permcath. further diagnostic evaluations showed that the distal part of the shaldon catheter implanted for hemodialysis about 10 months ago remained in chest as a foreign body (figure 1). no additional findings were reported in endoscopy of the upper gastrointestinal tract and bronchoscopy. echocardiography also confirmed the presence of two catheters in the heart excavations. after consultation with cardiothoracic surgery specialists, the patient underwent thoracotomy, and the foreign body was removed from the right atrium. the laboratory pathology report confirmed the presence of a foreign body. all complaints and symptoms disappeared, and the patient recovered after one week. in the three-month followup, her general health status was good, and there was no problem, except for the end-stage renal disease (esrd) outcome (hemodialysis three times a week). 3. discussion in this case, given the history of hemodialysis due to chronic renal failure, multiple hospitalizations, a systolic murmur in the cardiac examination, and laboratory test results (hypochromic microcytic anemia, high calcitonin, leukocytosis with a high neutrophil count, and esr), the patient was initially diagnosed with prolonged fever due to subacute endocarditis and underwent more accurate procedures. contrary to the opinion of the treatment staff, prolonged fever was due to a retained foreign body in the chest. as mentioned earlier, limited cases of retained catheters as foreign bodies have been reported. in this regard, schechter et al. (2013) performed a review study of retained intravascular devices since 2000. they reviewed 115 case reports and 19 case series, comprising 574 cases of retained intravascular devices as foreign bodies, only 5.6% of which were symptomatic (4). moreover, pokharel et al. (2015) performed a systematic analysis of case reports on retained central line guidewires (2). besides, schammer et al. (2001) reported four cases, including a 68-year-old male patient with septic shock and multiple organ failure after a rectal surgery, who underwent left femoral vein cannulation for hemofiltration by a fifth-year resident during the night shift; the routine chest radiography revealed a retained guidewire (5). in 2018, najari et al. reported the case of a patient who underwent femoral central venous catheterization due to the lack of a suitable peripheral vein. the patient was readmitted several days later due to pain and inflammation of the lower limb, as well as hematoma on the knee. doppler ultrasound of the lower extremity showed chronic deep vein thrombosis and several infectious areas without an echo. radiography and mri showed a retained guidewire in the right femoral vein (6). additionally, pei-jun li (2016) reported a case similar to the present case. a 61-year-old female patient with uremia had undergone intermittent hemodialysis for two years. a tunneled-cuffed catheter (tcc) was implanted in the right internal jugular vein for long-term access to the central vein due to two failures in arteriovenous hemofiltration. the catheter was replaced three times due to thrombosis and infection at the catheter site. due to dysfunction, two months after the third tcc implantation, large catheterrelated thrombosis was observed on the ultrasound. during the fourth tcc replacement, the catheter was suddenly broken at the site of attachment to the skin near the right internal jugular site. in the initial attempt, the clinician tried to remove the broken piece, but failed. the emergency x-ray fluoroscopy showed two free fragments of broken tcc in the right atrium and the inferior vena cava (7). according to a study by schechter, most reported cases are asymptomatic, and 37% were identified accidentally during imaging for other reasons (4). there were rare cases that were symptomatic, like the present study. for example, the case reported by hong loan nguyen et al. (2020) was a 39year-old male patient admitted to a hospital in the uk due to one week of lethargy, encephalopathy, and septic shock. the chest and abdominal radiography revealed the presence of a foreign body, and the chest ct scan showed multiple bilateral, peripheral, and nodular opacities following this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e49 table 1: laboratory findings of the presented case test value test value wbc (per microliter) 13800 (71% pmn) bun/cr 70/6 hemoglobin (g/dl) 11.5 fbs (mg/dl) 146 hematocrit (%) 28.8 na (meq/l) 146 platelet (per microliter) 110000 k (meq/l) 5.3 esr (mm/hour) 78 ca (meq/l) 8 crp +++ p (meq/l) 5.5 pt (ms) 14 precalcitonin (unit) 27 ptt (ms) 41 total bilirubin (mg/dl) 1.8 alt (iu/l) 25 direct bilirubin (mg/dl) 0.2 ast (iu/l) 31 alkaline phosphatase (iu/l) 98 wbc: white blood cell; pmn: polymorphonuclear; esr: erythrocyte sedimentation rate; crp: c-reactive protein; pt: prothrombin time; ptt: partial thromboplastin time; alt: alanine aminotransferase; ast: aspartate aminotransferase; bun: blood urea nitrogen; fbs: fasting blood sugar. figure 1: posterior-anterior (a), lateral (b), and anterior-posterior (c) views of patient’s chest x-ray. methicillin-sensitive staphylococcus aureus (mssa) infection. the foreign body was observed in the sub-segmental branch of the right upper pulmonary artery. abdominal and femoral interventions showed a left guidewire, extending from the inferior vena cava to the left common femoral vein. further investigations revealed that the patient had been admitted to the icu 16 years ago due to an accident and underwent central venous catheter placement in the inferior vena cava (8). in the case presented in our study, the catheter was removed through open thoracotomy. gabelman et al., in a review study of percutaneous retrieval and removal of the lost or misplaced intravenous instruments, reported 45 cases, including 12 retained stents, 14 retained catheters, 11 retained embolization coils, four retained left guidewires, and three retained vena cava filters (9). in our case, after discussions with experts invited to our medical team, due to the patient’s complaint of the anesthesiologist’s malpractice (the person in charge of removing the shaldon catheter), the anesthesiologist was sentenced to pay 5% of the fine. to prevent retained catheters, physicians and their assistant nurses should be careful about the used instruments in all medical procedures and check the items while removing them (6). it seems that use of radiography before and after catheter placement, as well as a checklist during the procedure, may help us rapidly identify and prevent similar cases. 4. conclusion when removing vascular catheters, it is necessary to ensure the complete removal of all appendages and conduct at least one simple x-ray of the patient’s chest or any other part of the patient’s body involved to prevent adverse and unanticipated events and avoid the possible physical and mental consequences. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. najari et al. 4 5. declarations 5.1. acknowledgment we would like to express our special thanks to the forensic center of tehran, iran. 5.2. authors’ contributions all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. 5.3. conflict of interest the authors declared no potential conflict of interest with respect to the authorship and/or publication of this article. 5.4. funding and supports none. 5.5. ethical considerations informed consent to use the medical information was obtained from the patient at the time of discharge from the hospital. references 1. mcgee dc, gould mk. preventing complications of central venous catheterization. new england journal of medicine. 2003;348(12):1123-33. 2. pokharel k, biswas bk, tripathi m, subedi a. missed central venous guide wires: a systematic analysis of published case reports. critical care medicine. 2015;43(8):1745-56. 3. sidiropoulou z, joão p, vasconcelos p, couceiro c. right subclavian vein catheterism complication due to a’foreign body’: a case report. journal of medical case reports. 2010;4(1):1-3. 4. schechter ma, o’brien pj, cox mw. retrieval of iatrogenic intravascular foreign bodies. journal of vascular surgery. 2013;57(1):276-81. 5. schummer w, schummer c, gaser e, bartunek r. loss of the guide wire: mishap or blunder? british journal of anaesthesia. 2002;88(1):144-6. 6. najari f, amirian m, sadjadi s, kayal ib. loss of guide wire as an important complication of central venous catheterization; a case report. emergency. 2018;6(1). 7. li p-j, liang z-a, fu p, feng y. removal of a fractured tunneled cuffed catheter from the right atrium and inferior vena cava by percutaneous snare technique. the journal of vascular access. 2016;17(3):e42-e3. 8. nguyen hl, herrera ln, cheema a, sarkar pk. broken and forgotten: a case of unintentionally retained foreign object. respiratory medicine case reports. 2020;29:101000. 9. gabelmann a, kramer s, gorich j. percutaneous retrieval of lost or misplaced intravascular objects. american journal of roentgenology. 2001;176(6):1509-13. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (1): 12-17 12 original research causes of sudden cardiac death on autopsy findings; a four-year report dinesh rao1*, divya sood2, p. pathak2, sudhir.d dongre2 1. executive director and chief of forensic pathologist, legal medicine unit, kingston, jamaica 2. department of pathology, sapthagiri institute of medical sciences and research center, bangalore, india abstract introduction: incidence of sudden cardiac death (scd) has been steadily increasing all over the world. while knowing the cause of scd is one of the favorites of the physicians involved with these cases, it is very difficult and challenging task for the forensic physician. the present report is a prospective study regarding cause of scds on autopsy examination in four-year period, bangalore, india. methods: the present prospective study is based on autopsy observations, carried out for four-year period from 2008 to 2011, and analyzed for cause of scds. the cases were chosen as per the definition of sudden death and autopsied. the material was divided into natural and unnatural groups. finally, on histopathology, gross examination, hospital details, circumstantial, and police reports the cause of death was inferred. results: a total of 2449 autopsy was conducted of which 204 cases were due to scd. the highest scds were reported in 50-60 years age group (62.24%; n-127), followed closely by the age group 60-69 (28.43%; n-58). male to female ratio was around 10:1. the maximum number of deaths (n=78) was within few hours (6 hours) after the onset of signs and symptoms. in 24 (11.8%) cases major narrowing was noted in both the main coronaries, in 87 (42.6%) cases in the left anterior descending coronary artery (lad), and in 18 (51.5%) cases in the right coronary artery (rca). the major cardiac pathology resulting in sudden death was coronary artery disease (n-116; 56.86%) and myocardial infarction (n-104; 50.9%). most of the scds occurred in the place of residence (n-80; 39.2%) followed closely by death in hospital (n-49; 24.01%). conclusion: coronary occlusion was the major contributory cause of sudden death with cardiac origin and the highest number of deaths were reported in the age 50-59 years with male to female ratio of 10:1. key words: cause of death; sudden; cardiac; coronary artery disease; autopsy cite this article as: rao d, sood d, pathak p, dongre sd. causes of sudden cardiac death on autopsy findings; a four-year report. emergency. 2014;2(1):12-7. introduction: 1 ncidence of sudden cardiac death (scd) has been steadily increasing all over the world particularly in the urban population during last five decades (1, 2). in india incidence of ischemic heart disease has increased, to about 10 percent (3). as revealed in autopsy findings, majority of sudden and unexpected deaths result as a sequel to cardiovascular disease (4). probably the most common cause of death recorded in autopsy is myocardial infarction (mi) due to coronary artery insufficiency (coronary occlusion due to atheroma and coronary thrombosis) (5). knowing the cause of sudden death is always one of the favorites of the physicians involved with these cases. on the other hand, a very difficult and challenging task for the forensic physician, conducting the autopsy, is to ascertain cause and nature of death (6, 7). one difficulty which is mostly encountered in sudden unexpected deaths, whether cardiac or no cardiac, is the lack of precision of collecting anteced *corresponding author: dinesh rao; department of forensic medicine, no 15, chikkasandra, hesargatta main road, sapthagiri institute of medical sciences and research center, bangalore, india. phone/fax +9741360206; email: dineshrao22@yahoo.com received: 30 january 2014; accepted: 11 february 2014 ent factors involved within the 24-hours, duration prior to death (8). for example, in certain cases of atrial fibrillations and spasms of coronary as a cause of death, the complete relaxation of coronary leaves no trace of such spasm, even though the death was due to coronary ischemia during autopsy. many time it has been seen that when gross pathology could not help to evaluate the cause of death, the histology came forward to rescue the situation and a conclusive opinion could be given on the involved cardiac pathology (9, 10). based on the above mentioned, the present report is a prospective study regarding cause of scd on autopsy examination in four-year period, bangalore, india. methods: study design and setting the present study is a prospective cross-sectional study carried during the 4-year period from january 2008 to december 2011 in kingston, jamaica and bangalore, india. a total of 2449 cases were chosen as per definition of sudden death and autopsied. all the cases were handed over for autopsy after completion of police/magistrate inquest. the material was divided into natural and unnatural deaths on the basis of underlying cause after analyzing the autopsy, police reports, and i this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 13 emergency (2014); 2 (1): 12-17 hospital records. hence, the cause of death was inferred on histopathology, gross examination, hospital details, circumstantial, and police reports. participants the size of the population limited to the jurisdiction for this autopsy study was around 1,200,000-1,500,000. the cases were deemed medico legal and involved individuals of all age group, sex, religion, caste, and nationality. all were referred as sudden onset of death and deemed as suspicious deaths. the study was focused only on scd and death from causes other than cardiovascular pathology was excluded. autopsy methods the heart was dissected as per the davidsons technique (11) and the ventricles were cut transversely to have the view of endocardium, its color, scars and fibrosis. the tissue were preserved in 10% formal saline, thickness of 3-5 millimeters was kept for fast and better fixation and stained with haematoxylin and eosin (200 gram aluminium ammonium sulphate, 20 gram haematoxylin, 40 milliliter ethanol, 4 gram sodium iodate, 80 milliliter acetic acid, 1200 milliliter glycerol, 2800 milliliter distilled water). autopsy analysis was focused on the details of morbid findings of the heart consisting of surface, walls, coronaries, valves, and great vessels, weight of heart, ostias, and papillary mussels. the weight was taken as normal of below 325 grams, in cases of males, and below 275 grams in cases of females (12, 13). the mi was considered recent if hemorrhages, paleness, and softening had been observed in the myocardium, and had the following microscopic changes: cytoplasmic hypereosinophilia, contraction band, granularity, lack of nuclei edema, and hemorrhage. all scars more than 0.5 centimeters (usually triangular in shape directed towards the apex) were considered as an old infarct along with the microscopic findings. definitions sudden death was defined as one which has taken place within 24 hours from the onset of symptoms and signs of disease, based on world health organization (who) definition (3, 4). also, sudden deaths in a short period was defined as deaths occurred within 30 minutes, either in hospital or when being brought to hospital or died within minutes after development of symptoms. the coronary occlusion was classified on rule of thumb that is slight narrowing, 30%; moderate narrowing 50%; and severe narrowing that is 70% and above (14). statistical analysis descriptive analyses were performed by statistical software spss version 11.0 and graphs drawn by excel 2013. data were shown as frequency and percentage. results: a total of 2449 cases were autopsied during the study period. two hundred four cases of scd were enrolled (90.2% male and 76.0% out of hospital) (figure 1). male to female ratio was 10:1. table 1 shows the demographic data of the subjects. twenty two (10.8%) cases had been found dead without any complaint of illness prior to the admission in casualty. forty one (20.1%) cases were known as ischemic heart disease but in apparent good health at the time of incidence. thirty three (16.2%) cases died in short period, 78 (38.2%) within few hours of onset of symptoms, 63 (30.9%) after 24 hours. in 30 (14.7%) cases duration of onset of symptoms and death could not be evaluated, due to nonavailability of specific history. the higher income group was more affected [78 (38.2%) cases], followed closely by the lower income group [60 (28.4%) cases] and the least group affected were from the middle class [27 (13.2%) cases]. the weight of the heart was above normal in 126 (61.8%) cases (minimum 150 grams, maximum 890 grams) (figure 2). sweating was noted in 159 (77.9%) cases, dyspnea in 136 (66.7%), precordial pain in 161 (78.9%), vomiting in 157 (77.0%), cyanosis, and exhaust looking face in 110 (53.9%). coronary artery disease was the most common cardiac pathology in these series [116 (56.86%) cases] (figure 3). the majority of deaths were occurred out of the hospital [155 (75.99%) cases]. details of coronary artery pathology figure four shows the anatomical location and block percentage of atheromatous and atherosclerotic lesion. table 1: demographic variable of scd  variable n % gender male 184 90.2 female 20 9.8 age (year) 15-19 1 0.5 20-29 0 0.0 30-39 3 1.5 40-49 15 7.4 50-59 127 62.3 60-69 58 28.4 70-above 0 0.0 socio-economical class low income class 60 29.4 middle income class 27 13.2 high income class 78 38.2 unclassified population 39 19.1 place of death outside the hospital* 155 76.0 hospital deaths 49 24.0 year of death 2008 42 20.6 2009 50 24.5 2010 51 25.0 2011 61 29.9 duration of onset of symptoms and death instantaneous(<30min) 33 16.2 early(<6hrs) 78 38.2 delayed(<24hrs) 63 30.9 unknown 30 14.7 * death while transportation to hospital 27 (13.2%) cases; scd: sudden cardiac death. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 14 rao et al figure 1: distribution of various causes of death both natural and unnatural from jan 2008 to dec 2011.  figure 2: weight of heart in grams.  in 24 (11.8%) cases, the major blockage was noted in both main coronaries, in 87 (42.6%) cases in the left anterior descending coronary artery (lad) and in 18 (51.5%) cases in the right coronary artery (rca). there were two cases which showed equally severe involvement of the cerebral vessel. the most frequent affected site was proximal 3-5 centimeters of anterior descending branch of lad from its origin. types of occlusion observed from concentric central pinhole type to crescentic with lumen pushed to one side of vessel. the highest incidence in all three vessels (circumflex, lad, and rca) was encountered in the age group of 5059 years. the younger cases showed a higher incidence in the lad. the incidence of severe occlusion in lad was 48.53% and in rca 8.82% (figure 4). the coronary artery least affected by blockage was left circumflex and left main trunk. mi cases were 49 (24.0%) recent and 55 (27.0%) old. in four (2.0%) cases the myocardium showed no evidence of healed or fresh infarcts. 1456 228 204 174 164 68 58 34 26 26 8 3 0 200 400 600 800 1000 1200 1400 1600 n u m b e r o f d e a th causes of death 9 24 42 54 33 18 0 12 6 3 0 10 20 30 40 50 60 150-200 201-250 251-300 301-350 351-400 401-450 451-500 501-550 551-600 601-650 n u m b e r o f d e a th heart weight (geram) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 15 emergency (2014); 2 (1): 12-17 figure 3: type of cardiac pathology. cad: coronary artery disease; mi: myocardial infarction; vr: ventricular rupture; rhd: rheumatic heart disease; hhd: hypertensive heart disease; hcm: hypertrophic cardiomyopathy; acm: alcoholic cardiomyopathy; ah: aneurysm of heart; rcm: restrictive cardiomyopathy.  figure 4: percentage of blockage of coronary artery.  discussion: based on the results of this study, coronary occlusion was the major contributory cause of scd, with incidence of 56.9% of all scd. male to female ratio has been found to be 10:1. in all cases the atherosclerotic process involved in varying extent, in both coronaries and their major branches. the highest number of scds was reported in the age of 50-59 years. the socio-economic status affected equally both low and high income groups. kuller et al. showed that nearly two third of sudden non-traumatic deaths are due to arteriosclerotic diseases (15). in addition, harmon et al. demonstrated that scd is the leading cause of death in athletes (2). the age-related trend of scd increases with age regardless of sex or race (16). in this context, the highest prevalence is in the geriatric age group (75-85 years) (17). for example, one study demonstrated that sudden death from coronary artery disease is six times more common at age between 60-69 while for those over 80 it is only two fold (18). the average age in the present series was between ages 50-59 years. similar age incidence has been observed in the study series of pentilla to be given 55-66 years (19). it is well-established that men have a higher incidence of scd than women (16, 17, 20, 21). the present study shows higher male to female ratio (10:1). framingham studied that scd was 10 times more among male than females (22). the male to female ratio at the incidence of coronary heart disease was reported from 3:2 to 8:1 (20, 23-25). in addi116 104 18 13 12 9 6 6 5 2 2 1 0 20 40 60 80 100 120 140 n u m b e r o f d e a th type of pathology 6 87 6 18 48 54 36 33 45 3 39 54 0 10 20 30 40 50 60 70 80 90 100 left main trunk left anterior descending left circumflex right coronary n u m b e r o f e v e n t involned artery 70-100% 40-70% 30 or less this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 16 rao et al tion to age and sex, socio-economic status has substantially impacted on incidence of scd (26-28). our result revealed that the socio-economic status affected low and high income groups. this can be attributed to indiscriminate habit of food and grains as well as other factors like smoking, junk foods, alcohol, and stress in both class of population. in involvement frequency, lad observed to have a higher severe narrowing than rca. gradwhol quoted the ranges from various published analysis as lad to be 45-64%, while rca come next in frequency, 24-46% followed by left circumflex 3-10%, and least affected in left main coronary (29). the observed variations among different series may be due to the regional variations on different cross section of the studied group to different periods. limitations during the comparison of unexpected scd results of this study with observations of similar field, the certain factors have been considered. firstly, the population under the study belonged to a cosmopolitan urban population; it is clear that some of them came from different regions of the country. secondly, though most autopsy investigations are meticulously followed by police authorities, there are skipped cases by omissions which are probably unavoidable in this vast country. while, there were many sophisticated methods of diagnosing myocardial infarction in postmortem examination like three tesla magnetic resonance imaging (3t-mri), immune-histochemical detection of s100 calciumbinding protein a1 (s100a1), and quantitative myoglobin assay (30-32); however, those investigations were not carried out to find the cause of death in the present study. lastly, the material available during the last four years was good enough to match with the works done by other researchers in similar field elsewhere. conclusion: coronary occlusion was the major contributory cause of scd and the most numbers of deaths were reported in the age 50-59 year with male to female ratio 10:1. acknowledgments: authors acknowledge department of pathology jawaharlal nehru institute of postgraduate medical research institute, pravara medical trust of loni, india, kingston public hospital of jamaica, and sapthagiri institute of medical science and research center. conflict of interest: none funding support: none authors’ contributions: rao d conducted the autopsy, authored the report, grossing of the organs and examined the slides under the microscope. dongre p extended their histopathology lab and support group. sood d participated in slide reading and histopathology in few cases. all authors wrote the first draft of the manuscript and approved the final version. references: 1. goldberger jj, basu a, boineau r, et al. risk stratification for sudden cardiac death a plan for the future. circulation. 2014; 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10(1): e89 rev i ew art i c l e prevalence and mortality of post-traumatic acute kidney injury in children; a systematic review and meta-analysis mahmoud yousefifard1,2, amirmohammad toloui1, seyed ali forouzannia3, neamatollah ataei2,4, hasti hossein1, amirali zareie shab khaneh5, maryam karimi ghahfarokhi5, michael e. jones6, mostafa hosseini2,5∗ 1. physiology research center, iran university of medical sciences, tehran, iran. 2. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 4. department of pediatric nephrology, children’s hospital medical center, tehran university of medical sciences, tehran, iran. 5. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 6. division of genetics and epidemiology, the institute of cancer research, london, uk. received: july 2022; accepted: august 2022; published online: 7 november 2022 abstract: introduction: numerous studies on acute kidney injury (aki) following trauma have been performed, and acceptable findings have been reported in the adult population. the present meta-analysis summarizes the studies performed on the pediatric population to evaluate the prevalence of aki following trauma in this population. methods: the medline, embase, scopus and web of sciences databases were searched for articles published until the july, 31, 2021. two independent reviewers screened observational studies performed on children with physical trauma and aki related to it. the interested outcomes were the prevalence and mortality of traumarelated aki in traumatized children. results: data of 9 articles were included in the present meta-analysis. the prevalence of trauma-related aki varied between 0% and 30.30% among included studies. pooled analysis showed that the prevalence of trauma-related aki was 9.86% (95% ci: 8.02 to 11.84%). the prevalence of aki after exertional rhabdomyolysis, direct physical trauma, and earthquake related injuries was 0%, 12.64% and 24.60%, respectively. there was a significant relationship between the prevalence of aki and trauma etiology (p = 0.038). moreover, the occurrence of aki in children with trauma was associated with an increased risk of mortality (or = 5.55; 95% ci: 2.14 to 13.93). conclusion: the findings of the present study showed that 9.86% of children develop aki following trauma, which may increase their risk of death by about 5.5 times. nevertheless, since none of the studies had adjusted their analyzes for potential confounders, caution should be exercised in interpreting the relationship between trauma-related aki and mortality. keywords: multiple trauma; pediatrics; acute kidney injury; earthquakes; exercise; rhabdomyolysis cite this article as: yousefifard m, toloui a, forouzannia sa, ataei n, hossein h, zareie a, et al. prevalence and mortality of posttraumatic acute kidney injury in children; a systematic review and meta-analysis. arch acad emerg med. 2022; 10(1): e89. https://doi.org/10.22037/aaem.v10i1.1660. 1. introduction acute kidney injury (aki) is a serious complication in children and adolescents. it is caused by many different etiologies and if not diagnosed in time, it can quickly progress to ∗corresponding author: mostafa hosseini; department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127, orcid: 0000-0002-1334-246x. chronic kidney disease and dialysis. the prevalence of aki indicates that about 10% of children admitted to the intensive care unit develop aki (1). this injury significantly affects patients’ mortality (1, 2). the risk of developing aki increases in both children and adults following trauma. this is due to direct damage to the kidneys, shock, the use of harmful compounds for the kidneys in the diagnosis and treatment of trauma patients, and the occurrence of rhabdomyolysis (3). current evidence show that the risk of mortality in traumatized children with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 2 aki could be 3.6 times higher (4). however, there is still considerable diversity among studies. in the last 20 years, numerous studies have been performed on aki following trauma, and acceptable findings have been reported in adults (5-8). however, the extent of the problem in children and the effect of aki on trauma mortality are not well understood. based on this, the researchers of the present study intended to provide evidence by conducting a systematic review and meta-analysis on the prevalence of aki and its relationship with mortality in traumatized children. 2. methods 2.1. study design and search strategy the present meta-analysis was designed to summarize the evidence of studies performed on pediatric samples to evaluate the prevalence of aki in traumatized pediatric patients. for the present study, the moose guideline, a guide for systematic review and meta-analysis in observational research has been used (9). an extensive search of the medline, embase, scopus and web of sciences electronic databases was conducted for articles published until the end of may 2020. the search strategy was based on keywords related to aki, trauma and prevalence. to refine the search, the recommended cochrane childhood cancer group filter was used to find articles related to children (10). table 1 presents the search strategy for the medline database. 2.2. inclusion criteria the definition of peco in the present study was as follows: problem or study population (p): children and adolescents with trauma; exposure (e): exposure to physical trauma; comparisons (c): with non-aki group; and outcome (o): prevalence of aki in children with trauma and their mortality. therefore, the observational studies performed on traumatized children with aki were included. exclusion criteria were adult patients, studies performed on non-traumatic aki, patients without aki, penetrating injuries, and caseseries studies. 2.3. data collection and quality assessment two independent researchers collected the data. after conducting the search and integrating the findings obtained from databases and searching the gray literature (search in google and google scholar as well as a search in the dissertation section of proquest database), the researchers performed an initial screening in the endnote program (version 8.0), independently. title and abstract of each article were studied and if the article was relevant or likely to be relevant, the full text of the study was retrieved and reviewed. the data of these studies were then summarized in a checklist designed based on prisma statement guidelines (11). the extracted data included information related to the study design, sample baseline characteristics (age, sex, etc.), number of samples studied, definition of aki, prevalence of aki and prevalence of mortality. the articles’ risk of bias was assessed using the national heart, lung, and blood institute quality assessment tool for observational cohort and cross-sectional studies (12). in case of any disagreements, the dispute was resolved through discussion with a third reviewer. 2.4. statistical analysis analyses were performed using stata 14.0 statistical program. all studies were summarized based on the studied outcomes. these outcomes were the prevalence of aki in traumatized children and its relationship with mortality. prevalence data were recorded as frequency. for evaluating the prevalence of trauma-related aki, the “metaprop_one” command was used and a pooled prevalence with 95% confidence interval (95% ci) was reported. the relationship between trauma-related aki and children’s mortality, was assessed using the “metan” command and pooled effect size was reported as odds ratio (or). the presence of heterogeneity was investigated using the i2 statistics. since we expected no obvious heterogeneity among studies, a fixed effect model was used for the analyses. in case of heterogeneity, we used random effect model, and performed subgroup analysis to find the source of heterogeneity. egger’s test and funnel plot were used to examine publication bias. 3. results 3.1. summary of studies the search yielded 3311 non-duplicated articles. after the initial full-text screening, 37 articles were reviewed and finally the data of 9 articles were included in the present metaanalysis (figure 1) (13-21). there were 3 prospective cohort studies and 6 retrospective cohort studies. the etiology of trauma among patients in the included studies were direct physical trauma, exercise-related injuries, exertional rhabdomyolysis, or earthquake. these studies included data from 1,052 traumatized children. table 2 shows a summary of the characteristics of included articles. 3.2. risk of bias in the quality control section, it was realized that none of the studies reported the prevalence of aki in terms of severity of trauma (item 8); also, the sample size calculation was reported in only one study (item 5). none of the studies adjusted the analyses for potential confounders (item 14). moreover, the blinding status of the outcome observer was not reported in any of the studies (item 12) (table 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e89 3.3. meta-analysis • prevalence of trauma-related aki in children the prevalence of trauma-related aki varied between 0% and 30.30% among included studies. pooled analysis showed that the prevalence of trauma-related aki was 9.86% (95% ci: 8.02 to 11.84%) (figure 2). to investigate the cause of heterogeneity in the prevalence of aki, subgroup analysis was performed based on the etiology of aki. table 4 shows the findings of this section. accordingly, the prevalence of aki after exertional rhabdomyolysis, mild to severe direct trauma, and earthquakerelated injuries was 0%, 12.64% and 24.60%, respectively; according to this analysis, there is a significant difference between the prevalence of aki in terms of trauma etiology (p = 0.038). • relationship between trauma-related aki and mortality in children in this section, data from 7 studies were entered. the prevalence of mortality following trauma-related aki in children is low (table 2). however, the analysis showed that the occurrence of aki in traumatized children was associated with an increased odds ratio (or) of mortality (or = 5.55; 95% ci: 2.14 to 13.93). nevertheless, since none of the studies had adjusted their analyzes for potential confounders, caution should be exercised in interpreting the findings of this section (figure 3). 3.4. publication bias egger’s test showed that there wasn’t any publication bias in assessment of the prevalence of trauma-related aki in children (p = 0.72) and relationship of trauma-related aki with children’s mortality (p = 0.154) (figure 4). 4. discussion the present meta-analysis summarized the current evidence on the relationship between trauma and the incidence of aki in children. the findings of the present study showed that 9.86% of children develop aki following trauma, which may increase their risk of mortality by about 5.5 times. the analyses of the present study showed that the cause of trauma is an important factor in the occurrence of aki. the prevalence of aki following exertional rhabdomyolysis is zero percent, while the prevalence increases with injury severity. therefore, as a report, it can be said that the occurrence of aki in children with exertional rhabdomyolysis is very rare, while almost a quarter of children with severe injuries or earthquake victims develop aki. a finding that calls for more attention in the management of children with trauma, especially those admitted to intensive care units with severe traumas. one of the aims of the present study was to investigate the relationship between the incidence of aki following trauma in children and adolescents and the pertaining mortality. although the findings of the present meta-analysis showed that the incidence of aki is associated with an increased risk of death in traumatized children, care should be taken in interpreting this finding. risk of bias assessment in the present study showed that none of the studies attempted to adjust the analyzes for potential confounders of mortality in trauma patients and therefore the observed relationship between the incidence of aki and mortality of traumatized children may be a confounding relationship. furthermore, the quality of studies was moderate, most studies were retrospective in nature, and the blinding of the outcome assessor was unclear. therefore, in order to accurately determine the prevalence of aki in children with trauma, it is necessary to design studies with a larger sample size and higher quality. another limitation in the present study was the difference in the definition of aki in included studies. for example, in the study of prodhan et al., they used the prifle criteria to define aki, and defined all classes of risk, injury, failure, and end-stage as aki (20). whereas, in the standard definition, the risk category is not defined as documented aki. therefore, to overcome this problem, the risk category was left out to use a similar definition of aki among included studies. nonetheless, two studies (18, 19) did not provide the definition of aki. 5. conclusion for the first time, the present meta-analysis summarized the existing reports on the relationship between trauma and the incidence of aki in children. the findings of the present study showed that 9.86% of children develop aki following trauma, which may increase their risk of death by about 5.5 times. 6. declarations 6.1. acknowledgments none. 6.2. conflict of interest statement the authors declare that they have no conflict of interests. 6.3. compliance with ethical standards this study complies with the declaration of helsinki and all ethical standards. 6.4. human and animal rights this article does not contain any studies with human participants or animals performed by any of the authors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 4 6.5. funding the study was funded and supported by tehran university of medical sciences (tums); grant no: 98-01-184-42135. 6.6. conflict of interest none. references 1. schneider j, khemani r, grushkin c, bart r. serum creatinine as stratified in the rifle score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. crit care med. 2010;38(3):933-9. 2. goldstein sl, devarajan p. pediatrics: acute kidney injury leads to pediatric patient mortality. nat rev nephrol. 2010;6(7):393-4. 3. harrois a, libert n, duranteau j. acute kidney injury in trauma patients. curr opin crit care. 2017;23(6):447-56. 4. haines rw, fowler aj, kirwan cj, prowle jr. the incidence and associations of acute kidney injury in trauma patients admitted to critical care: a systematic review and meta-analysis. j trauma acute care surg. 2019;86(1):141-7. 5. burmeister dm, gomez bi, dubick ma. molecular mechanisms of trauma-induced acute kidney injury: inflammatory and metabolic insights from animal models. biochim biophys acta mol basis dis. 2017;1863(10 pt b):2661-71. 6. civiletti f, assenzio b, mazzeo at, medica d, giaretta f, deambrosis i, et al. acute tubular injury is associated with severe traumatic brain injury: in vitro study on human tubular epithelial cells. sci rep. 2019;9(1):6090. 7. perkins zb, captur g, bird r, gleeson l, singer b, o’brien b. trauma induced acute kidney injury. plos one. 2019;14(1):e0211001. 8. ramirez me, mcquillan rf. acute kidney injury secondary to trauma-induced hemolysis: the need for increased awareness and a preventative strategy. am j kidney dis. 2017;69(2):320. 9. stroup df, berlin ja, morton sc, olkin i, williamson gd, rennie d, et al. meta-analysis of observational studies in epidemiology: a proposal for reporting. meta-analysis of observational studies in epidemiology (moose) group. jama. 2000;283(15):2008-12. 10. leclercq e, leeflang mmg, van dalen ec, kremer lcm. validation of search filters for identifying pediatric studies in pubmed. j pediatr. 2013;162(3):629-34.e2. 11. moher d, liberati a, tetzlaff j, altman dg. preferred reporting items for systematic reviews and metaanalyses: the prisma statement. ann intern med. 2009;151(4):264-9. 12. national institutes of health. national heart lung, and blood institute. quality assessment tool for observational cohort and cross-sectional studies 2014 [available from: https://www.nhlbi.nih.gov/health-topics/studyquality-assessment-tools. 13. bjornstad ec, muronya w, smith zh, gibson k, mottl ak, charles a, et al. incidence and epidemiology of acute kidney injury in a pediatric malawian trauma cohort: a prospective observational study. bmc nephrol. 2020;21(1):1-12. 14. chen c-y, lin y-r, zhao l-l, yang w-c, chang y-j, wu k-h, et al. clinical spectrum of rhabdomyolysis presented to pediatric emergency department. bmc pediatr. 2013;13(1):134. 15. guardenier a, peterson b, hilfiker m, shellington d. 1170: acute renal failure in pediatric patients after moderate to severe traumatic brain injury. crit care med. 2015;43(12):294. 16. hatamizadeh p, najafi i, vanholder r, rashid-farokhi f, sanadgol h, seyrafian s, et al. epidemiologic aspects of the bam earthquake in iran: the nephrologic perspective. am j kidney dis. 2006;47(3):428-38. 17. iskit sh, alpay h, tuğtepe h, özdemir c, ayyıldız sh, özel k, et al. analysis of 33 pediatric trauma victims in the 1999 marmara, turkey earthquake. j pediatr surg. 2001;36(2):368-72. 18. lin h, chie w, lien h. epidemiological analysis of factors influencing an episode of exertional rhabdomyolysis in high school students. am j sports med. 2006;34(3):481-6. 19. oh jy, laidler m, fiala sc, hedberg k. acute exertional rhabdomyolysis and triceps compartment syndrome during a high school football camp. sports health. 2012;4(1):57-62. 20. prodhan p, mccage ls, stroud mh, gossett j, garcia x, bhutta at, et al. acute kidney injury is associated with increased in-hospital mortality in mechanically ventilated children with trauma. j trauma acute care surg. 2012;73(4):832-7. 21. talving p, karamanos e, skiada d, lam l, teixeira pg, inaba k, et al. relationship of creatine kinase elevation and acute kidney injury in pediatric trauma patients. j trauma acute care surg. 2013;74(3):912-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e89 table 1: search strategy in medline database database search terms medline (pubmed) 1. “wounds and injuries”[mh] or "injuries"[subheading] or “multiple trauma”[mh] or “hemolysis”[mh] or “rhabdomyolysis”[mh] or trauma[tiab] or traumas[tiab] or multiple trauma[tiab] or polytrauma[tiab] 2. “prevalence”[mh] or “epidemiology”[mh] or “incidence”[mh] or prevalence[tiab] or epidemiology[tiab] or incidence[tiab] or incidence rate[tiab] or epidemiologic[tiab] 3. ("acute kidney injury"[mesh terms] or ("acute"[all fields] and "kidney"[all fields] and "injury"[all fields]) or "acute kidney injury"[all fields]) or ("acute kidney injury"[mesh terms] or ("acute"[all fields] and "kidney"[all fields] and "injury"[all fields]) or "acute kidney injury"[all fields] or ("acute"[all fields] and "renal"[all fields] and "failure"[all fields]) or "aki"[all fields]) 4. (infan* or newborn* or new-born* or perinat* or neonat* or baby or baby* or babies or toddler* or minors or minors* or boy or boys or boyfriend or boyhood or girl* or kid or kids or child or child* or children* or schoolchild* or schoolchild or school child[tiab] or school child*[tiab] or adolescen* or juvenil* or youth* or teen* or under*age* or pubescen* or pediatrics[mh] or pediatric* or paediatric* or peadiatric* or school[tiab] or school*[tiab] or prematur* or preterm*) 5. #1 and #2 and #3 and #4 table 2: the summary of the characteristics of eligible studies author; year; country study type population age sample size number of boys aki definition aki mortality in aki mortality in non-aki bjornstad; 2020; malawi prospective cohort mild to severe trauma 8.1 114 42 kdigo criteria 11 4 6 chen; 2013; taiwan retrospective cohort trauma and exercise related injury 10.2 12 26 serum creatinine level of more than the 97.5th percentile 0 0 0 guardenier; 2015; united states retrospective cohort moderate to severe tbi 0-17 years 35 18 prifle 5 0 0 hatamizadeh; 2006; iran retrospective cohort earthquake victims 0-15 49 not specified at least 2 reported serum creatinine values of 1.6 mg/dl or greater 14 not specified not specified lin; 2005; taiwan prospective cohort exertional rhabdomyolysis high school student 157 106 not specified 0 0 0 oh; 2011; united states retrospective cohort exertional rhabdomyolysis 15.9 43 not specified not specified 0 0 0 iskit; 2001; turkey retrospective cohort earthquake victims 8.8 33 17 serum creatinine level above 1.2 mg/dl or oliguria 10 0 0 prodhan; 2012; united states retrospective cohort severe icu admitted trauma 11.6 88 58 prifle 22 7 5 talving; 2013; united states retrospective cohort mild to severe trauma 12.2 521 352 prifle 70 not specified not specified aki: acute kidney injury; kdigo: kidney disease improving global outcomes; prifle: pediatric risk, injury, failure, loss , end stage renal disease; tbi: traumatic brain injury; icu: intensive care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 6 figure 1: prisma flow diagram of the present study. aki: acute kidney injury. figure 2: prevalence of acute kidney injury in traumatized children. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e89 figure 3: the pooled odds ratio (or) of mortality following trauma-related acute kidney injury (aki) in children. the risk of mortality of is higher in traumatized children with aki compared to non-aki children. figure 4: assessment of publication bias among included studies. there is no publication bias in the present meta-analysis. aki: acute kidney injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 8 table 3: risk of bias assessment of included studies according to national heart, lung, and blood institute quality assessment tool for observational cohort and cross-sectional studies (12) study items 1 2 3 4 5 6 7 8 9 10 11 12 13 14 bjornstad; 2020 yes yes yes yes yes yes yes no yes na yes nr yes no chen; 2013 yes yes yes yes nr yes yes no yes na yes nr nr no guardenier; 2015 yes yes yes yes nr yes yes no yes na yes nr nr no hatamizadeh; 2006 yes yes yes yes nr yes yes no yes na yes no nr na lin; 2005 yes yes yes yes nr yes nd no yes na yes no nr no oh; 2011 yes yes yes yes nr yes nd no yes na yes no nr no iskit; 2001 yes yes yes yes nr yes nd no yes na yes nr no no prodhan; 2012 yes yes yes yes nr yes yes no yes na yes nr nd no talving; 2013 yes yes yes yes nr yes yes no yes na yes nr no no yes: low risk of bias; no: high risk of bias; na: not applicable; nd: not determined; nr: not reported. table 4: the prevalence of acute kidney injury (16) stratified by the etiology of trauma etiology of aki number of studies prevalence (95% ci) heterogeneity (p value) exertional rhabdomyolysis 3 0.00 (0.00 to 0.20) 0.0% (>0.999) all severities 2 12.64 (10.14 to 15.37) 0.0% (>0.999) moderate to severe rhabdomyolysis in earthquake 4 24.60 (18.81 to 30.86) 0.0% (>0.999) among subgroups 0.038 ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e19 or i g i n a l re s e a rc h propofol + granisetron vs. propofol + metoclopramide in symptom management of acute migraine headache; a double-blind randomized clinical trial samaneh abiri1, mehdi chegin1, reza soleimani2, naser hatami2, navid kalani3, esmail rayatdoost1∗ 1. department of emergency medicine, research center for noncommunicable diseases, jahrom university of medical sciences, jahrom, iran. 2. student research committee, jahrom university of medical sciences, jahrom, iran. 3. research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. received: january 2022; accepted: february 2022; published online: 5 march 2022 abstract: introduction: acute headache is one of the most common reasons for emergency department (ed) visits. this study aimed to compare the combination of propofol and granisetron with propofol and metoclopramide in symptom management of acute migraine headache. methods: in this double-blind randomized clinical trial, 60 adult patients with acute migraine headache who referred to ed were randomly divided into two groups of propofol + metoclopramide and propofol + granisetron. pain and nausea/vomiting severity as well as blood pressure were compared between groups 30, 45, and 60 minutes after treatment. results: the two groups had similar situation regarding mean age (p = 0.606), sex distribution (p = 0.793), baseline severity of pain (p = 0.642), frequency of nausea/vomiting (p = 0.488), and vital signs (p > 0.05). the severity of pain was similar in the two groups 30 (p = 0.731), 45 (p = 0.460), and 60 (p = 0.712) minutes after treatment. the number of patients with resistant nausea and vomiting 60 minutes after treatment was significantly higher in metoclopramide group (30.0% versus 10.0%; p = 0.033). diastolic pressure 60 minutes after treatment (81.43 ±8.94 vs. 74.97 ± 4.8; p = 0.001) and heart rate 30 minutes after treatment (68.87 ±6.52 vs. 73.57± 7.62; p = 0.013) had statistically significant differences between the groups. conclusion: the combination of propofol and granisetron was superior to propofol and metoclopramide in case of controlling nausea and vomiting of cases with acute migraine headache; meanwhile, no differences were observed in case of pain relief and hemodynamic status between the two groups. keywords: propofol; granisetron; metoclopramide; migraine disorders cite this article as: abiri s, chegin m, soleimani r, hatami n, kalani n, rayatdoost e. propofol + granisetron vs. propofol + metoclopramide in symptom management of acute migraine headache; a double-blind randomized clinical trial. arch acad emerg med. 2022; 10(1): e19. https://doi.org/10.22037/aaem.v10i1.1561. 1. introduction headache is one of the most common types of pain that make many patients go to pain clinics or emergency departments (ed). in the united states, 90% of the population experienced a headache, 50% of the population suffered from one type of headache, and 25% experienced recurrent and debilitating attacks (1). according to a study done in the united ∗corresponding author: esmail rayatdoost; department of emergency medicine, jahrom university of medical sciences, jahrom, iran. email: e.rayat.dost@gmail.com/ tel: 00989177396014, orcid: http://orcid.org/00000002-9430-7913. states, headaches cost the us economy more than $50 billion a year, resulting in decreased work and educational efficiency as well as a significant increase in medical expenditures for the us health system. migraine is the most frequent form of headache, and it can cause incapacity, as well as a loss of financial resources and a reduction in the efficiency of work and education. at least once a year, 15-20 percent of women and 6-10 percent of men suffer from migraines. it has been revealed that the age ranges of 25-55 years have the highest occurrence (2). migraine disorders, including classic migraine, are caused by spasms of cerebral arteries, and migraine pain is caused by subsequent dilation of extra cranial arteries (3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. abiri et al. 2 migraine headaches often present as one-sided, throbbing pains and are accompanied by nausea and vomiting, sensitivity to light, and fatigue (4-6). current prophylactic treatments usually include dopamine receptor antagonists such as prochlorperazine or metoclopramide, which are often combined with diphenhydramine. studies have shown that these drugs are safer and more effective than nonsteroidal anti-inflammatory drugs and sumatriptan (7-10). metoclopramide stops the effects of dopamine on the central nervous system and other organs. its effects on the medulla oblongata (ctz) region suggest that it is a beneficial antiemetic for nausea and vomiting, while it may be an 5-ht3 receptor antagonist. it should also be noted that granisetron is a potent selective 5-ht3 antagonist that is primarily used to treat nausea due to chemotherapy. side effects include headache, diarrhea, constipation, anxiety, and insomnia (12). another recommended treatment for acute migraine is an anesthetic agent called propofol. the mechanism of action of propofol is through its agonist activity on the gamma-aminobutyric acid (gaba) aminobutyric acid (gabaa) beta 1 subunit, which leads to hyperpolarization and inhibition of neuronal stimulation (13). this study aimed to compare the use of propofol + granisetron with propofol + metoclopramide in symptom management of patients who referred to the emergency department (ed) with migraine headache. 2. methods 2.1. study design and setting the present study is a double-blind randomized clinical trial that was performed during a one-year period from june 2018 to june 2019 on patients with acute migraine headache who referred to ed of peymaniyeh hospital, jahrom, iran. before the patients were included in this study, the research process was explained and informed consent was obtained from them. throughout the study, researchers adhered to the principles of helsinki declaration and confidentiality of patient information. all costs of the project were covered by the researchers and no additional costs were incurred by the patients. this study has been approved by the ethics committee of jahrom university of medical sciences under the ethical code ir.jums.rec.1397.060 and has been registered in the iranian registry of clinical trials under the number irct20201003048903n2. (http: //www.irct .ir). 2.2. participants adult patients (18 years old or older) without history of head trauma in recent months, no abnormal neurological findings, and no hearing or verbal impairment with the criteria of migraine headache based on international headache society’s definition (2 to 8 headache episodes per month in the previous 3 months, with or without aura) were included. patients with moderate to severe pain (visual analogue scale (vas) > 3) were included. patients who had taken other medication for pain relief before presenting to the ed, those with history of allergy to the studied drugs, pregnant cases, cases with unstable hemodynamic or loss of consciousness, and finally cases not agreeing to enter the study were excluded (14). 2.3. intervention patients were randomly divided into 2 groups: 1) propofol and granisetron and 2) propofol and metoclopramide, using simple random sampling method by tossing coins. the person performing the work steps, the person collecting the information, and the patient were unaware of the type of drug used. all patients were under close clinical, electrocardiographic, pulse oximetry, and non-invasive blood pressure monitoring during the procedure. patients in group one received intravenous (iv ) bolus dose of 2 mg granisetron (caspian tamin pharmaceutical co., iran) over 3 minutes plus 10 mg propofol 1% (aram pharmaceutical co.,ltd , iran) over 3 minutes (every 5 to 10 minutes up to a maximum dose of 80 mg) through cephalic, basilic, or any available superficial veins of the hands; patients in group two received 10 mg metoclopramide (caspian tamin pharmaceutical co., iran) over 3 minutes plus 10 mg propofol 1% over 3 minutes (every 5 to 10 minutes up to a maximum dose of 80 mg). propofol injections continued until the headache resolved. 2.4. outcomes pain and nausea/vomiting management were considered as the primary measured outcomes of the study. hemodynamic changes (blood pressure and heart rate) were considered as the secondary outcomes. pain and nausea/vomiting severity were measured before the injection of the drugs and at intervals of 30, 45 and 60 minutes after the injection. nurses were blinded to type of treatment as medications were provided in syringes in packets and also patients did not know the exact medication type. we planned pethidine administration as the rescue treatment in cases of resistant pain. 2.5. data collection the checklist designed by the researcher included demographic information (age, sex), history of headache, severity of pain, nausea and vomiting score, and vital signs (systolic and diastolic blood pressure, heart rate). the severity of pain was assessed using a visual acuity pain score, in which zero indicates no pain and ten indicates unimaginable pain. also, the score of nausea and vomiting (0 = without nausea and vomiting, 1 = mild nausea without the need for treatment or curable nausea, 2 = nausea that can be relieved with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e19 table 1: comparing the baseline characteristics between the two groups variable granisetron metoclopramide p* age (year) less than 30 3 (10.0) 1 (3.3) 30-50 14 (46.6) 16 (53.3) 0.606 more than 50 13 (43.3) 13 (43.3) sex male 17 (56.6) 18 (60.0) 0.793 female 13 (43.3) 12 (40.0) blood pressure (mmhg) systolic 142.7±17 139.2 ±15.5 0.108 diastolic 73.97 ± 4.8 75.43± 8.9 0.432 heart rate (beats/minutes) mean ± sd 69.87±6.52 70.87±6.52 0.371 pain severity (vas) mean ± sd 5.5 ±2.29 5.2 ±2.4 0.642 nausea/vomiting severity before treatment no nausea/vomiting 4 (13.3) 6 (20.0) 0.488 treatable 26 (86.7) 24 (80.0) data are presented as mean ± standard deviation (sd) or frequency (%). vas: visual analog scale. table 2: comparing the outcomes between the two studied groups 30, 45, and 60 minutes after injections variables granisetron metoclopramide p 30 minutes 3.87 ±2.06 4.1 ±2.2 0.731 45 minutes 3.3 ± 1.56 3.6 ±1.6 0.460 60 minutes 3.6 ±1.61 3.9 ±1.8 0.712 systolic blood pressure (mmhg) 30 minutes 146.4 ±18.3 147.1 ±18.6 0.222 45 minutes 140. 4 ±15.2 140.1 ±14.9 0.344 60 minutes 145.8 ±18.5 147.1 ±18.6 0.113 diastolic blood pressure (mmhg) 30 minutes 75.96 ± 4.79 77.43 ±8.94 0.433 45 minutes 76.97 ±4.8 78.43 ±8.94 0.188 60 minutes 74.97 ± 4.8 81.43 ±8.94 0.001 heart rate (beat/minute) 30 minutes 68.87 ±6.52 73.57± 7.62 0.013 45 minutes 69.87±6.52 71.87±6.52 0.146 60 minutes 73.57±7.62 72.57±7.62 0.704 nausea/vomiting 60 minutes after injection mild 13 (43.3) 3 (10.0) curable 7 (23.3) 9 (30.0) 0.033 treatable 3 (10.0) 3 (10.0) resistant 3 (10.0) 9 (30.0) data are presented as mean ± standard deviation or frequency (%). vas: visual analog scale. anti-nausea medication or treatable nausea, 3= interactable nausea and vomiting) was used for measuring the severity at baseline and 60 minutes after the treatment. 2.6. data analysis data analysis was performed using spss software version 21 and intention to treat analysis. data were reported using mean ± standard deviation or frequency (percentage). repeated measurement anova, chi-square, and independent t were used for comparisons. p <0.05 was considered as level of significance. also, we calculated number needed to treat (nnt) and absolute risk reduction (arr)(15). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. abiri et al. 4 figure 1: the consort flow chart of the randomized trial. 3. results 3.1. baseline characteristics 60 cases with acute migraine headache were randomly divided into two 30-case groups. table 1 compares the baseline characteristics between groups. the two groups were similar regarding mean age (47.43±15.25 in granisetron and 48.80 ±13.38 years in metoclopramide group; p = 0.606), sex distribution (p = 0.793), history of headache (p = 0.606), baseline severity of pain (p = 0.642), and vital signs (p > 0.05). regarding nausea and vomiting, 4 patients in granisetron group and 6 patients in metoclopramide had no nausea and vomiting; while other patients needed treatment for nausea and vomiting based on our scoring (p=0.488). 3.2. outcomes table 2 compares the outcomes between the two studied groups at different times after injections. the severity of pain was similar in the two groups at 30 (p = 0.731), 45 (p = 0.460), and 60 (p = 0.712) minutes after treatment. the number of patients with resistant nausea and vomiting 60 minutes after treatment was significantly higher in metoclopramide group (30.0% versus 10.0%; p = 0.033). although there was a statistically significant difference between the groups regarding diastolic pressure 60 minutes after treatment (81.43 ±8.94 vs. 74.97 ± 4.8; p = 0.001) and heart this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e19 rate 30 minutes after treatment (68.87 ±6.52 vs. 73.57± 7.62; p = 0.013), these differences were not clinically important. the pain was relieved in all cases and no case needed rescue treatment in the two groups. in granisetron group, intractable or resistant vomiting rate in 60 minutes was less than metoclopramide group (10% vs. 30%) with nnt of 5 (arr=0.2). 4. discussion the results of this study showed that the combination of propofol and granisetron has a similar effect to propofol and metoclopramide regarding pain management and a superior effect regarding controlling nausea/vomiting after 60 minutes in patients presenting to ed following acute migraine headache. the two combinations had similar effects on vital signs. the effects of metoclopramide and granisetron on migraine headaches and nausea in migraine sufferers were examined by amiri et al. the level of pain was recorded using the vrs scale at intervals of 1 to 4 hours in this study, and the patients’ nausea and vomiting condition was also assessed. the findings of amiri et al.’s study were similar to ours in that the incidence of nausea and vomiting in the granisetron group was considerably lower than in the metoclopramide group at all time intervals after taking the medicine. similar to our study, there was no significant difference in the incidence of headache between the two study groups (16). medications used to treat migraines fall into two groups: suppressive or preventive. there are many options for treating acute migraine. in the present study, we focused on the combination of metoclopramide and granisetron with propofol for the treatment of headache, nausea, and vomiting in an acute migraine attack. metoclopramide is an antiemetic agent that blocks dopamine and serotonin receptors in the cns chemoreceptor hub receptor. granisetron is a selective 5-ht3 antagonist that binds to receptors in the peripheral and central nervous systems with primary effects on the golgi apparatus (17). leyasin et al. concluded that granisetron and metoclopramide gel have similar effects in the management of postoperative nausea and vomiting in obstetric and gynecological surgeries and that granisetron has no superiority over metoclopramide in prevention of nausea and vomiting. in contrast, we found granisetron to be better than metoclopramide in treating migraine pain (18). bojan bagi and colleagues compared the effect of dexamethasone in combination with metoclopramide and granisetron on postoperative nausea and vomiting. the results of their study showed that the incidence of nausea and vomiting in the group receiving the combination of dexamethasone with metoclopramide was not significantly different from the group receiving granisetron. in fact, in this study, the effects of dexamethasone in combination with metoclopramide and granisetron in controlling nausea and vomiting after surgery were very similar and this study showed that the effectiveness of dexamethasone in combination with metoclopramide is not low compared with granisetron. this study was in line with the positive effects of granisetron and metoclopramide in controlling and reducing nausea and vomiting (19). akerman et al. studied the effect of metoclopramide. it inhibits the excitability of vascular neurons, which is highly predictive of the anti-migraine action of this drug (20). another study evaluated the antiemetic effects of ondansetron and granisetron in preventing postoperative nausea and vomiting in a patient undergoing laparoscopic surgery. this study showed that the incidence of severe nausea and vomiting was 7% among patients receiving intravenous granisetron, followed by 20% in the ondansetron group and 50% in the placebo group (22). the results of this study are in line with our study regarding the effect of granisetron. in our study, the number of patients with severe nausea and vomiting resistant to treatment in the granisetron group was significantly lower than the number these patients in the metoclopramide group. we have shown that the effect of granisetron on nausea and headache is relatively higher than that of metoclopramide. in line with the results of our study, in a randomized double-blind study on 100 female patients, the effect of granisetron and ondansetron in preventing nausea and vomiting was evaluated in patients undergoing elective laparoscopic cholecystectomy. there was a significant difference between the two groups and the incidence of nausea and vomiting in the granisetron receiving group was significantly lower than the incidence of nausea and vomiting in the group receiving ondansetron (23). gauchan et al. evaluated the antiemetic effect of ondansetron and granisetron in patients undergoing laparoscopic cholecystectomy during the first 24 hours after anesthesia. they showed that granisetron was able to effectively reduce the incidence of nausea and vomiting compared to ondansetron in the first 24 hours (24). in line with the results of the present study, in another study by savant et al., the effects of ondansetron and granisetron on preventing nausea and vomiting in the patients undergoing oral and maxillofacial surgery were investigated. the results of this study showed that the incidence of nausea and vomiting in the granisetron group was significantly lower than ondansetron. patients receiving granisetron showed a higher rate of a headache compared to the ondansetron group (25). in contrast, in our study the incidence of headache after drug injection was not significantly different from that of metoclopramide. in one study, mohammed and colleagues examined the effects of metoclopramide and ondansetron on the control of postoperative nausea and vomiting. the results of their study showed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. abiri et al. 6 that metoclopramide was more effective than ondansetron in controlling nausea and vomiting after surgery (26). this was also confirmed in malekshoar et al.’s study(27). 5. strength and limitations the strength of this study was using the combination of these medications so that a statistically and clinically significant decrease in pain score was recorded in both groups. we did not record the number of propofol doses for each group to be able to compare the groups in this regard, this might have biased the conclusion. another limitation of this study was the low number of patients, which might be a possible reason for the absence of difference in pain reduction properties of medications. also, we did not assess the other patient characteristics as well as any painkiller being consumed before referral and time from initiation of symptom to presentation to ed. 6. conclusion the results of this study showed that the effect of propofol and granisetron combination was similar to propofol and metoclopramide combination regarding pain management; but it had a superior effect regarding controlling nausea/vomiting after 60 minutes in patients presenting to ed following acute migraine headache. both combinations had similar effects on vital signs. 7. declarations 7.1. acknowledgments we would like to thank the clinical research development unit of peymanieh educational and research and therapeutic center of jahrom university of medical sciences for providing facilities to this work. 7.2. authors’ contributions er conceptualized the study design and rs and nk wrote the study protocol. rs and nk collected the data and analyzed it. manuscript was drafted by nk and er. all authors contributed to the revisions. 7.3. funding and supports the research was financially supported by jahrom 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nazir s, nissa g. comparative evaluation of ondansetron and granisetron in prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy in females. iosr. 2013; 4: 15-20. 24. gauchan s, thapa c, shakya p, bhattarai r, shakya s. ondansetron and granisetron for prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy. journal of nepal medical association. 2014;52(193):682-6. 25. savant k, khandeparker rvs, berwal v, khandeparker pv, jain h. comparison of ondansetron and granisetron for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia: a prospective, randomised, and double blind study. journal of the korean association of oral and maxillofacial surgeons. 2016;42(2):84-9. 26. abdul kareem mohammed z, ahmed jawad s, salih mahdi m, fowzi ibrahim w. a comparative study for the effect of ondansetron and metoclopramide in prevention of postoperative nausea and vomiting. journal of kerbala university. 2017;13(3):20-7. 27. malekshoar m, jarineshin h, kalani n, vatankhah m. comparing the effect of metoclopramide and promethazine on preventing nausea and vomiting after laparoscopic cholecystectomy: a double-blind clinical trial. koomesh journal. 2021;23(2):203-10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strength and limitations conclusion declarations references emergency. 2017; 5 (1): e57 or i g i n a l re s e a rc h the pattern of pre-hospital medical service delivery in iran; a cross sectional study mashyaneh haddadi1, mohammad sarvar1, hamid soori2, elaheh ainy2∗ 1. disaster and emergency management center, ministry of health and medical education, tehran, iran. 2. safety promotion and injury prevention research center of shahid beheshti university of medical sciences, research affair department, tehran, iran. received: october 2016; accepted: january 2017; published online: 19 february 2017 abstract: introduction: pre-hospital emergency systems provide service by franco-german and anglo american models. this study was carried out to compare the iranian emergency medical service (ems) with the two models regarding timing and equipment. methods: in this cross sectional study, response time, scene time, and transport time to hospital as well as ambulance equipment of five hundred thousand tehran ems recorded missions, during one year, were compared with franco-german and anglo american models, trying to determine the pattern of ems delivery in iran. results: the mean response time, scene time, and transport time to hospital were 15.00 ±10.88, 18 ±11.48, and 15.00 ±11.20 minutes, respectively. the mean response time (p<0.035), scene time (p<0.033), and transport time to hospital (p<0.015) were more than the standard time. percentage of ambulances quipped with automated external defibrillator (45%, p<0.001), ventilator (2%, p<0.001), disposable splint (0%, p<0.001), and wheelchair (0%, p<0.001) were very far from standards. conclusion: the pattern of ems delivery in iran was a combination of anglo american and franco-german system. keywords: equipment safety; emergency medical service; response latency; ambulances © copyright (2017) shahid beheshti university of medical sciences cite this article as: haddadi m, sarvar m, soori h, ainy e. the pattern of pre-hospital medical service delivery in iran; a cross sectional study. emergency. 2017; 5(1): e57. 1. introduction p re-hospital care with emergency medical services (ems) can play a major role in the secondary and tertiary prevention (1). legal medicine organization of iran announced that from 2006 to 2010 more than half of those killed by traffic accidents died at the scene, and 9 to %16 died during transport to the hospital (2). pre-hospital accident cares initiated by the first proceeding at the scene (informing efficient and rescue forces, rapid delivery of ems personnel, suitable release, the correct diagnosis, and early treatment measures) and continued during transport to hospital (3). in countries and regions where pre-hospital care is well-designed and good quality services is delivered to victims of traffic accidents, deaths and disabilities from road traffic injuries is greatly reduced. the united nations road ∗corresponding author: elaheh ainy; safety promotion and injury prevention research center, shahid beheshti university of medical sciences, arabi ave, daneshjoo blvd, velenjak, tehran, iran. email: ainy.elaheh@gmail.com tel: 0098 21 22439784 safety collaboration has developed a global plan for the decade of action for road safety 2011-2020 with five categories or “pillars” of activities. improving post-crash response is one of the pillars (4). ems provides service by two models, namely franco-german and anglo american. in franco-german model, physicians and medical staff can treat the victims with high-tech equipment on the scene and in germany, france, greece, malta, austria has developed favorably. however, in anglo american model, which is used in some countries such as united states of america, united kingdom, canada, new zealand, the sultanate of oman, and australia, patients are sent to the hospital quickly with minimal pre-hospital interventions (1, 5). each of the francogerman and anglo american models follow a special pattern and have special education facilities and the provision of services. in some countries, including the uk pre-hospital medical services are offered through the health system (6). in iran, disaster and emergency management center of ministry of health is responsible for ems, but the pattern of prehospital medical services delivery is not well defined. this study was carried out, to compare the iranian emergency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haddadi et al. 2 medical services (ems) with the two mentioned models regarding response time, scene time, and transport time to hospital. 2. methods 2.1. study design and setting in this cross sectional study, trying to determine the pattern of pre-hospital medical delivery in iran, response time, scene time, and transport time to hospital of five hundred thousand tehran ems recorded missions, over a period of one year (first of august 2015 to first of august 2016), were compared with selected countries: germany and france (with franco-german system) and united states and united kingdom (with anglo-american system). the protocol of the study was approved by ethics committee of shahid beheshti university of medical sciences. 2.2. participants five hundred thousand recorded missions registered by the automation system of tehran ems center during the study period were enrolled. those who attended the emergency centers themselves were excluded because their response time was zero. 2.3. data gathering the data regarding ems’s response time, scene time and transport time to hospital were gathered. data were extracted from global positioning system (gps) monitored missions registered by the automation system of tehran ems center. according to the national mandatory standard n0:4374 all ambulances must be equipped. ambulances’ equipment have been delivered based on the mentioned standard (7). the data of two studied models regarding the times and needed equipment in pre-hospital care were extracted via a literature search in several databases including pubmed and transport research international documentation (trid), cochrane and web of science. the notions of response time, scene time and transport time to hospital were also reviewed in a broad context. 2.4. definitions most researchers in the recent years have divided the total out of hospital time to a number of “intervals”, including a response time (time from ems system activation to presence of an ambulance on the scene), scene (or on-scene) time (time that an ambulance spends on the scene to the beginning of departure), and transport time (time from the beginning of departure to patient’s arrival at the emergency department). 2.5. franco-german model of pre-hospital care in this model: doctor is brought to the patient; care is often provided by emergency physicians; based on the “stay and stabilize” philosophy; fewer transports to the hospital; direct transport to inpatient wards; utilizes more extensive advanced technology; widely implemented in europe; ems as part of public health organization (1, 8). 2.6. anglo-american model of pre-hospital care in this model: patient is brought to the doctor; care provided by emergency medical technicians/paramedics; based upon the “scoop and run” philosophy; more patients transported to the hospital; brought to the emergency department; more likely to be found in countries with emergency medicine as a developed specialty; widely implemented in english speaking countries globally (1, 8). 2.7. statistical analysis all analyses were carried out using epi info software (version 7.2. developed by centers for disease control and prevention (cdc) in atlanta, georgia, usa). data were reported as mean ± standard deviation or frequency and percentage. a bivariate analysis was conducted using chi square and t test. p values < 0.05 were considered statistically significant. 3. results 3.1. baseline characteristics 500000 tehran ems recorded missions were studied. doctors and nurses are present in 4.9% of ambulances (type c ambulances) and in the majority of ambulances (type b ambulances) two technicians are present (95.1%). the education levels of the ems staff were technicians in 80.4% (60.4% associate degree and 20% with medical emergency training) and bachelors and master of science in 19.6% of cases. 3.2. comparisons table 1 and 2 compare the studied pre-hospital medical service deliveries with anglo-american and franco-german models regarding the times and equipment. the mean response time (p<0.035), scene time (p<0.033), and transport time to hospital (p<0.015) were very far from standards. in addition, percentage of ambulances equipped with automated external defibrillator (45%, p<0.001), ventilator (2%, p<0.001), disposable splint (0%, p<0.001), and wheelchair (0%, p<0.001) was significantly lower than the standards. 100% of studied ambulances were equipped with long backboard, traction splint, and electric suction, similar to francogerman and anglo american models. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e57 table 1: comparison of studied pre-hospital medical service deliveries with anglo-american and franco-german models regarding time management times iran anglo-american franco-german standard response 15.0 (14.6) 10.0 (8.0) 20.9 (15.0) 6.0-8.0 scene 18.0 (17.5) 21.2 (19.0) 32.6 (30.0) 8.0-10.0 transport 15.0 (14.5) 23.3 (20.0) 19.9 (15.0) 15.0-20.0 all times in minutes. data were presented as mean (median) or range. table 2: comparison of studied pre-hospital medical service deliveries with anglo-american and franco-german models regarding equipment equipment iran anglo-american franco-german standard aed* 45 60 60 100 ventilator 2 100 100 100 long backboard 100 100 100 100 traction splint 100 100 100 100 disposable splint 0 30 50 100 wheelchair 100 100 100 100 vacuum suction 100 100 100 100 *: automated external defibrillator. data were presented as percentage and extracted from following references (1, 5, 6, 8, 10-13, 23-26). 4. discussion findings showed that the pattern of ems delivery in iran was a combination of anglo american and franco-german system. pre-hospital emergency medical service of iran was reachable through a nationwide 115 number, but other numbers such as, 110 (police), 112 (rescue), and 125 (fire) to report traffic accidents and relief services can also be used. notification to relief centers is conducted with delay due to lack of universal access number (uan) and the joint dispatch. creating a unique relief number reduces the rate of delay in relief. it seems that franco-german emergency system has significant drawbacks compared to anglo american system. in anglo american model the educational level of ems staff is as follows: 13.2% physicians, 84.5% nurses, and 2.3% emergency medical technicians (9). in franco-german system physicians and medical staff should treat the victims with high-tech equipment on the scene. emergency trauma patients are treated at the scene of an accident and during transport by emergency physicians. rescuers are often the first to arrive at the accident scene and may use defibrillator, carry out endotracheal intubation, and administer some drugs such as endotracheal epinephrine and intravenous glucose until reaching the doctor. it is guaranteed that the emergency patients are reached in up to 8 minutes in %80 and 15 minutes in %95 of the cases (10-16). in franco-german model qualified emergency physicians and paramedics provided standard care. the entire pre-hospital time and scene time is just slightly longer than anglo american system. there are specific training programs for emergency physicians, ems staff and medical director of emergency system managers. resuscitation is not only performed by anesthesiologists but also internists, surgeons or pediatricians. medical emergency includes cardiopulmonary resuscitation, the shock cases, myocardial infarction, acute stroke, poly-trauma, and status asthma. in franco german system incidence of mortality in trauma victims has decreased from 830 thousand annual deaths (%10) to less than %4 (17, 18). the anglo-american model is bringing patients to the hospital with less pre-hospital interventions quickly. the system has been run by trained paramedics and emergency medical technicians with a clinical supervision. countries which use anglo-american model of ems delivery include the united states, united kingdom, canada, new zealand, sultanate of oman and australia (19-22). it seems that ems must be presented by an organization that is capable of delivering the best health care services and works with other healthcare providers as well as social service and public safety agencies. the pattern of emergency in iran was a combination of anglo american and franco-german systems. factors such as traffic, poor roads, and remote and out of reach areas, and inadequate relief helicopters are the causes of delay for pre-hospital care in the emergency cases. pre-hospital services deviate from standards due to lack of adequate equipment. on the other hand, due to the lack of safety standard in auto industry of iran, severity of injury is high in car accidents. it is proposed that pre hospital emergency system of iran should follow a single pattern either franco german or anglo american system and have the required equipment this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. haddadi et al. 4 according to the selected pattern. automobile safety must be strongly supervised by authorities in automotive industry. the number of emergency air ambulances must be increased. urban and rural roads must be modified by the ministry of roads and urban development. according to the condition of cities, equipped emergency bases must be built in high risk areas. iranian emergency personnel should be supported financially and psychologically for their hard work. the study was carried out for the first time in iran and five hundred thousand missions have been investigated. study was conducted on registered missions of tehran emergency over a one year period that could be the strength of the study. 5. limitation this was a cross sectional study. cross sectional studies provide a snapshot of the frequency of a disease or other health related characteristics in a population at a given point in time. method of treatment and patients’ satisfaction were not recorded. these could be the limitations of the study. 6. conclusion the pattern of ems delivery in iran was a combination of anglo american and franco-german system. therefore, it is suggested to follow a single pattern and be equipped in accordance with the selected model. 7. appendix 7.1. acknowledgements authors are willing to express their gratitude to safety promotion and injury prevention research center of shahid beheshti university of medical sciences, tehran, iran for scientific support. 7.2. authors’ contribution mashyaneh haddadi: designing, coordination, analysis, article writing. elaheh ainy: designing, data gathering management, analysis, article writing. mohammad sarvar: data gathering management, analysis, article writing. hamid soori: supervision, analysis, article writing. 7.3. funding/support no funds. 7.4. conflict of interest there is no conflict of interest. references 1. al-shaqsi s. models of international emergency medical service (ems) systems. oman med j. 2010;25(4):320-3. 2. moradi s, khademi a, jarotani m. victims of car accidents looks at the statistics in eighties of tehran: institute of legal medicine; 2002. 3. calland v. extrication of the seriously injured road crash victim. emergency medicine journal. 2005;22(11):81721. 4. sminkey ml. global plan for the decade of action for road safety 2011-2020. world health organization www who int/roadsafety/decade_of_action. 2011. 5. al-shaqsi s. current challenges in the provision of ambulance services in new zealand. international journal of emergency medicine. 2010;3(4):213-7. 6. toroyan t, peden mm, iaych k. who launches second global status report on road safety. injury prevention. 2013;19(2):150-. 7. roudsari bs, nathens ab, arreola-risa c, cameron p, civil i, grigoriou g, et al. emergency medical service (ems) systems in developed and developing countries. injury. 2007;38(9):1001-13. 8. dick wf. anglo-american vs. franco-german emergency medical services system. prehospital and disaster medicine. 2003;18(01):29-37. 9. sittichanbuncha y, prachanukool t, sarathep p, sawanyawisuth k. an emergency medical service system in thailand: providers’ perspectives. journal of the medical association of thailand= chotmaihet thangphaet. 2014;97(10):1016-21. 10. blackwell th, kaufman js. response time effectiveness: comparison of response time and survival in an urban emergency medical services system. academic emergency medicine. 2002;9(4):288-95. 11. slovis cm, carruth tb, seitz wj, thomas cm, elsea wr. a priority dispatch system for emergency medical services. annals of emergency medicine. 1985;14(11):1055-60. 12. de segura nieva jlg, boncompte mm, sucunza ae, louis clj, segui-gomez m, otano tb. comparison of mortality due to severe multiple trauma in two comprehensive models of emergency care: atlantic pyrenees (france) and navarra (spain). the journal of emergency medicine. 2009;37(2):189-200. 13. grossman dc, kim a, macdonald sc, klein p, copass mk, maier rv. urban-rural differences in prehospital care of major trauma. journal of trauma and acute care surgery. 1997;42(4):723-9. 14. adnet f, jouriles nj, le toumelin p, hennequin b, taillandier c, rayeh f, et al. survey of out-of-hospital emergency intubations in the french prehospital medical system: a multicenter study. annals of emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e57 1998;32(4):454-60. 15. sethi d, aljunid s, sulong sb, zwi ab. injury care in low-and middle-income countries: identifying potential for change. injury control and safety promotion. 2000;7(3):153-64. 16. lerner eb, moscati rm. the golden hour: scientific fact or medical “urban legend”? academic emergency medicine. 2001;8(7):758-60. 17. minville v, pianezza a, asehnoune k, cabardis s, smail n. prehospital intravenous line placement assessment in the french emergency system: a prospective study. european journal of anaesthesiology. 2006;23(07):594-7. 18. platz e, bey t, walter fg. international report: current state and development of health insurance and emergency medicine in germany. the influence of health insurance laws on the practice of emergency medicine in a european country. the journal of emergency medicine. 2003;25(2):203-10. 19. pozner cn, zane r, nelson sj, levine m. international ems systems: the united states: past, present, and future. resuscitation. 2004;60(3):239-44. 20. symons p, shuster m. international ems systems: canada. resuscitation. 2004;63(2):119-22. 21. trevithick s, flabouris a, tall g, webber c. international ems systems: new south wales, australia. resuscitation. 2003;59(2):165-70. 22. hay h. ems in new zealand. emerg med serv. 2000;29(7):95-7,109. 23. page c. analysis of emergency medical systems across the world: worcester polytechnic institute; 2013. 24. pons pt, haukoos js, bludworth w, cribley t, pons ka, markovchick vj. paramedic response time: does it affect patient survival? academic emergency medicine. 2005;12(7):594-600. 25. swaroop m, straus dc, agubuzu o, esposito tj, schermer cr, crandall ml. pre-hospital transport times and survival for hypotensive patients with penetrating thoracic trauma. journal of emergencies, trauma, and shock. 2013;6(1):16. 26. eckstein m, alo k. the effect of a quality improvement program on paramedic on-scene times for patients with penetrating trauma. academic emergency medicine. 1999;6(3):191-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e73 or i g i n a l re s e a rc h attitudes of emergency nurses and patients’ family members towards the presence of family members during cardiopulmonary resuscitation; a cross-sectional study zohreh hosseini marznaki1, samad karkhah2∗ mehdi mohammadian amiri3, håkan källmen4, azadeh moradi5, maede najjarboura6 1. department of nursing, amol faculty of nursing and midwifery sciences, mazandaran university of medical sciences, sari, iran. 2. department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 3. department of emergency medicine, school of medicine, babol university of medical sciences, babol, iran. 4. centre for psychiatry research karolinska institutet, stockholm, sweden. 5. emam reza hospital, mazandaran university of medical sciences, sari, iran. 6. guilan university of medical sciences, rasht, iran. received: june 2022; accepted: july 2022; published online: 6 september 2022 abstract: introduction: family presence during cardiopulmonary resuscitation (cpr) is one of the elements where family-centered care is practiced. this study aimed to investigate the attitudes of iranian emergency nurses and patients’ family members regarding the presence of family during cpr. methods: in a cross-sectional study, 350 emergency nurses and 254 family members of patients admitted to the emergency department of an educational hospital in iran were enrolled. data were collected from may to november 2020 using convenience sampling and using a 27-item questionnaire of participants’ attitudes towards family presence during cpr. results: the mean attitude scores of nurses and family members of patients regarding family presence during cpr were 86.79 ± 7.50 and 92.48 ± 6.77, respectively (p < 0.001). the highest and lowest mean scores of nurses’ attitude towards family presence during cpr were related to "cpr performance will be negatively influenced" and "family members have the right to be present during cpr of their relatives/ allows relatives to stay with the patient until the end/ makes the patient less worried ", respectively. the highest and lowest mean scores of family members’ attitude towards family presence during cpr were related to "family members may interfere with cpr" and " may be beneficial to the relatives’ grieving process ", respectively. conclusion: overall, the results of this study showed that the attitude of emergency nurses and patients’ family members towards family presence during cpr was positive. of course, the mean attitude score of nurses in this regard was significantly lower. keywords: family; resuscitation; cardiopulmonary resuscitation; nurses; attitude; emergency service, hospital cite this article as: hosseini mz, karkhah s, mohammadian am, källmen h, moradi a, najjarboura m. attitudes of emergency nurses and patients’ family members towards the presence of family members during cardiopulmonary resuscitation; a cross-sectional study . arch acad emerg med. 2022; 10(1): e73. https://doi.org/10.22037/aaem.v10i1.1679. 1. introduction cardiac arrest occurs when a person’s heartbeat stops (1). according to the american heart association, 475,000 people in the united states experienced cardiac arrest in 2018 (2). car∗corresponding author: samad karkhah; department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. email: sami.karkhah@yahoo.com, tel: +989032598167, orcid: https://orcid.org/0000-0001-9193-9176. diopulmonary resuscitation (cpr) is an emergency lifesaving procedure that can reverse cardiac arrest (3). when cardiac arrest occurs for patients, their family members in the waiting room are informed of the patient’s condition by an emergency nurse (4, 5). patient and family-centered care have substantial benefits for the family, patients, and health care providers. family presence during cpr is one of the elements where familycentered care is practiced. family presence during cpr benefits the family and patients, and indeed healthcare profesthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem hm. hosseini et al. 2 sional guidelines exist on the implementation of cpr during family presence (6). an integrative review showed that family members would like to be present during cpr. however, the practice is rarely implemented by healthcare professionals (7). qualitative research in brazil found that the perspectives differ across family members, patients, and healthcare professionals about family presence during cpr. however, environmental, sociocultural, and care-related factors predict perspectives towards family presence during cpr (4, 8-10). in iran, the family is very valuable in culture and religion, and the presence of family members in the final moments of life is important (11). on the other hand, family presence during cpr is a challenging issue in iran (9). however, previous evidence in iran has shown that emergency nurses are not prepared for the presence of family members during cpr (4, 9, 12). for example, a study in iran showed that the attitudes of most emergency nurses and most patients’ family members towards family presence during cpr were negative (12). however, there is limited information on the attitudes of emergency nurses and patients’ family members towards family presence during cpr (13). therefore, the present study aimed to investigate the attitudes of iranian emergency nurses and patients’ family members regarding the family presence during cpr. 2. methods 2.1. study design and setting in a cross-sectional study, 350 emergency nurses and 254 family members of patients admitted to the emergency department of an educational hospital in amol, affiliated to mazandaran university of medical sciences, mazandaran were studied regarding their attitude towards the presences of patients’ family during cpr. data were collected from may to november 2020 using convenience sampling. this study was approved by the ethics committee of mazandaran university of medical sciences (ir.mazums.rec.1399.7820). the objectives of the study were explained to participants and informed consent was obtained from them. participants completed the questionnaires in a private room without the presence of a research team. 2.2. participants participation in this study was voluntarily. the nurses with the experience of caring for a patient who underwent cpr were included. in addition, family members of patients that underwent cpr, who were over 18 years old were included. participants who did not consent to participate in the present study were excluded. 2.3. data gathering data were collected using a two-part questionnaire including 1) participants ’demographic characteristics and 2) participants’ attitudes towards family presence during cpr. demographic characteristics of nurses such as age, sex, marital status, level of education, clinical work experience, employment status, shift work, tendency to work in a non-nursing profession, and work in a non-nursing profession were collected. also, baseline characteristics of family members of patients such as sex, marital status, level of education, and family member’s relationship to the patient, as well as the age of the patient who was resuscitated, and survival of the resuscitated relative were collected. the attitude towards family presence during the cpr questionnaire was designed by leung and chow (2012) (14). this tool consists of 27 items in four areas, including 1) attitudes towards patient and family member rights for family presence during the cpr (3 items; range of scores: 3 to 15), potential advantages of family presence during the cpr (8 items; range of scores: 8 to 40), potential disadvantages of family presence during the cpr (12 items; range of scores: 12 to 60), and opinions about supportive requirements for the implementation of family presence during the cpr (4 items; range of scores: 4 to 20). participants rate the items of this tool on a five-point likert scale from strongly disagree (score of 1) to strongly agree (score of 5) for the first 23 items and from very unimportant (score of 1) to very important (score of 5) for the last four items. this tool is scored between 27 and 135. in iran, the reliability of the present questionnaire was confirmed by zali et al., with a cronbach’s alpha of 0.763 (12). the questionnaire was pilot-tested on randomly selected nurses (10 in number) and family members (15 in number), and minor modifications were made (to resolve confusing wording) based on their feedback about the content, sentence structure, and clinical relevance. reliability was assessed, resulting in a cronbach’s alpha of 0.80, indicating high internal consistency. trained nurses contacted the family members of deceased patients by phone six months after the death and interviewed them. an individual interview was requested with the explanation of its purpose and an appointment in the hospital was made where appropriate specialists were informed and called for support (12). 2.4. statistical analysis the sample size of the family members was calculated using the formula of z 2 1−α/2×δ2 /d 2 with d=10% and 1-α =0.95. all statistical analyses were performed using spss for windows, version 16.0 (spss inc., chicago, il, usa). descriptive statistics were presented as mean ± standard deviation for continuous variables and frequency with percentage for catthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e73 table 1: baseline characteristics of nurses and their correlation with the mean attitude score regarding the presences of family during cardiopulmonary resuscitation variables nurses (n=350) attitude score p-value age (year) 20-25 35 (10.00) 87.65 ±6.30 26-35 227 (64.86) 86.45 ±7.50 0.029 36-45 65 (18.57) 85.82 ± 6.00 46-55 23 (6.57) 87.86 ± 8.48 gender male 56 (16.00) 85.19 ± 7.30 0.081 female 294 (84.00) 87.10 ± 7.50 marital status single 171 (48.86) 86.84 ± 7.33 0.470 married 179 (51.14) 86.74 ± 7.64 level of education in nursing bachelor of science 315 (90.00) 87.00 ± 7.66 0.110 master of science 35 (10.00) 84.94 ± 5.59 working experience (year) 7.11 ± 5.09 ≤10 296 (84.57) 86.71 ± 7.40 0.750 >10 54 (15.43) 87.25 ± 8.09 employment status temporary 192 (54.86) 86.65 ± 7.28 0.148 official 158 (45.14) 86.95 ± 7.45 work shift fixed 77 (22.00) 86.62 ± 7.44 0.320 rotational 273 (78.00) 87.77 ± 8.24 tendency to work in a non-nursing profession yes 143 (40.86) 87.07 ± 7.72 0.880 no 207 (59.14) 86.30 ± 7.17 working in a non-nursing profession yes 33 (9.43) 86.87 ± 7.60 0.260 no 317 (90.57) 86.09 ± 6.44 data are presented as frequency (%) and mean ± standard deviation. attitude score ranges from 27 to135. egorical variables. the kolmogorov-smirnov test was used to check the normality of data distribution. the association between attitudes of the two study groups was assessed using the pearson correlation test. independent t-test and one-way analysis of variance (anova) were used to compare groups. statistical significance was set to p < 0.05. 3. results 3.1. participants’ characteristics in the present study, 350 emergency nurses and 254 family members of patients were included. of the nurses, 64.86% had an age of 26-35 years, 84% were female, 90% had a bachelor of science in nursing (bsn) degree, and 84.57% had less than ten years of work experience. of the family members of patients, 59.45% were male, 79.13% were married, 38.19% had a degree less than a high school diploma, and 33.07% were children of patients. the baseline characteristics of participants are presented in tables 1 and 2. 3.2. attitude towards family presence during cpr the mean attitude score of nurses and family members of patients towards family presence during cpr were 86.79 ± 7.50 and 92.48 ± 6.77, respectively (p < 0.001). the highest and lowest mean scores of nurses’ attitude towards family presence during cpr were related to " cpr performance will be negatively influenced " and "family members have the right to be present during cpr of their relatives/ allows relatives to stay with the patient until the end/ makes the patient less worried ", respectively. the highest and lowest mean scores of family members’ attitude towards family presence during cpr were related to "family members may interfere with cpr" and " may be beneficial to the relatives’ grieving process ", respectively (table 3). 4. discussion the results of this study showed that the attitude of emergency nurses and patients’ family members towards family this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem hm. hosseini et al. 4 table 2: baseline characteristics of family members and their correlation with the mean attitude score regarding the presences of family during cardiopulmonary resuscitation variables family members (n=254) attitude score p-value age of patient (year) 10-20 9 (3.54) 97.11 ± 6.77 21-30 38 (14.96) 89.60 ± 6.48 31-50 145 (57.09) 92.73 ± 6.60 0.019 51-70 57 (22.44) 92.92 ± 6.83 71-90 5 (1.97) 93.80 ± 8.13 gender male 151 (59.45) 93.00 ± 6.43 0.140 female 103 (40.55) 91.72 ± 7.21 marital status single 53 (20.87) 91.72 ± 7.07 0.363 married 201 (79.13) 92.74 ± 6.59 level of education < high school diploma 97 (38.19) 92.60 ± 6.90 0.927 high school diploma 93 (36.61) 92.55 ± 6.64 college education or higher 64 (25.20) 92.20 ± 6.88 relationship to patient spouse 82 (32.28) 92.67 ± 7.11 child 84 (33.07) 92.35 ± 6.92 father 37 (14.57) 91.67 ± 6.64 0.702 mother 26 (10.24) 92.84 ± 5.48 sister or brother 25 (9.84) 94.11 ± 6.68 survival after resuscitation yes 34 (13.39) 91.73 ± 6.33 0.488 no 220 (86.61) 92.60 ± 6.85 data are presented as frequency (%) and mean ± standard deviation. attitude score ranges from 27 to 135. presence during cpr was positive. of course, the mean attitude score of nurses in this regard was significantly lower. this finding was not in line with the results of studies from brazil, (8) trinidad and tobago, (15) and iran (9). a study in brazil (8) found that health care providers had a negative attitude towards family presence during cpr. they believed that changes should be made to the hospital infrastructure to accommodate family members and train staff to meet the emotional needs of families during cpr (8). another study in trinidad and tobago found that families experienced psychological damage from cpr and that family presence during cpr prolonged the resuscitation process (15). also, a study in iran showed that emergency nurses have a negative attitude towards family presence during cpr, which can be improved through workshops (9). the attitude of nurses towards family presence during cpr is more positive in western countries compared to middle-eastern countries (16). a study in the usa found that nurses had a more positive attitude towards family presence during cpr than other health care workers (17). however, a study in singapore found that health care workers had a negative attitude towards family presence during cpr (6). this difference may be due to differences in the culture and religion of nurses (18). therefore, emergency nurses need to be prepared through workshops and effective policies in this area. also, well-designed interventions are essential to improve the attitude of emergency nurses towards family presence during cpr. the attitude of patients’ family members towards family presence during cpr was positive. consistent with this finding, a study in china (14) found that 80% of patients’ family members had a positive attitude towards family presence during cpr. a study in iran (12) showed that the presence of family members during cpr reduces their anxiety. also, another study in iran (19) found that family presence during cpr helps those present accept patients’ deaths more easily than their families. however, there is limited evidence regarding the attitude of family members of patients related to family presence during cpr, and there is no policy to support it. therefore, it is recommended that iranian researchers pay special attention to the attitude of family members of patients related to family presence during cpr in future studies. also, well-designed interventions to reduce the gap between the attitudes of nurses and family members and developing policies and workshops can help improve the attitude of emergency nurses regarding family presence during cpr. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e73 table 3: comparing the attitudes of nurses and family members regarding family presence during cardiopulmonary resuscitation (cpr) statement nurses (n=350) family (n=254) family members have the right to be present during cpr 2.02 ± 0.75 3.73 ± 1.05 permission should be obtained in advance, if possible, from the patient prior to witnessed cpr 2.47 ± 1.01 3.98 ± 0.89 i would be present during cpr of my relative if allowed 2.90 ± 1.24 3.73 ± 1.10 presence of family members would benefit the patient 2.85 ± 1.36 3.19 ± 1.32 allows relatives to ensure everything was done 2.18 ± 1.11 3.75 ± 1.11 allows relatives to stay with the patient until the end 2.02 ± 0.91 3.79 ± 1.09 makes the patient less worried 2.02 ± 0.91 2.51 ± 1.51 family members provide support to the patient 2.73 ± 1.21 3.85 ± 1.07 would benefit the family members 2.36 ± 1.03 3.88 ± 1.03 may be beneficial to the relatives’ grieving process 2.43 ± 1.02 1.87 ± 0.94 improves relatives’ understanding of cpr 2.86 ± 1.24 3.93 ± 1.00 may impair patient dignity 2.30 ± 0.97 3.79 ± 1.10 relatives may have a bad last impression of patient 4.18 ± 0.97 3.73 ± 1.16 process of cpr is too distressing to relatives 3.93 ± 1.24 2.76 ± 1.15 relatives may have long-term psychological sequel 4.02 ± 1.11 3.78 ± 1.03 family members may interfere with cpr 4.32 ± 0.89 4.40 ± 0.92 will prolong the cpr, making the decision to stop more difficult 4.06 ± 1.23 2.54 ± 1.19 increases the emotional stress of physicians 3.66 ± 1.30 2.05 ± 0.99 negatively influences the physicians’ performance 3.88 ± 1.20 1.96 ± 0.93 increases the emotional stress of nurses 3.84 ± 1.21 3.46 ± 1.23 negatively influences the nurses’ performance 4.38 ± 0.88 3.33 ± 1.20 cpr performance will be negatively influenced 4.44 ± 0.78 3.12 ± 1.19 may increase litigation or complaint 4.18 ± 1.15 4.12 ± 0.87 should be supported by a member of staff 2.15 ± 0.74 3.82 ± 0.96 facilities must be available to screen off the area where the cpr takes place to allow privacy 3.57 ± 1.22 3.60 ± 1.08 the physician should speak with or write to the relatives afterwards to discuss the cpr 3.40 ± 1.25 3.58 ± 1.17 if required, the doctor should arrange appropriate referrals for witnessing relatives 3.54 ± 1.05 4.12 ± 0.85 data are presented as mean ± standard deviation. the range of score for each question was 1 to 5. 5. limitation the present study had several limitations. the main limitation of this study was the lack of evaluation of patients’ attitudes towards family presence during cpr. the study also assessed the attitudes of emergency nurses and patients’ family members using a self-report questionnaire that may lead to a response bias. all responses were from one department at one single hospital, which may have a negative impact on external validity. 6. conclusion the results of this study showed that the attitude of emergency nurses and patients’ family members towards family presence during cpr was positive. of course, the mean attitude score of nurses in this regard was significantly lower. 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions study concept and design by all authors; data acquisition by all authors; data interpretation by all authors; drafting of the manuscript by all authors; revision of the manuscript by all authors; the final version of the manuscript is approved by all authors. 7.3. funding and supports none. 7.4. conflict of interest the authors declare no conflict of interest. 7.5. availability of data the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. references 1. sawyer kn, camp-rogers tr, kotini-shah p, del rios m, gossip mr, moitra vk, et al. sudden cardiac arrest this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem hm. hosseini et al. 6 survivorship: a scientific statement from the american heart association. circulation. 2020;141(12):e654-e85. 2. zègre-hemsey jk, grewe me, johnson am, arnold e, cunningham cj, bogle bm, et al. delivery of automated external defibrillators via drones in simulated cardiac arrest: users’ experiences and the human-drone interaction. resuscitation. 2020;157:83-8. 3. tanaka h, ong meh, siddiqui fj, ma mhm, kaneko h, lee kw, et al. modifiable factors associated with survival after out-of-hospital cardiac arrest in the panasian resuscitation outcomes study. annals of emergency medicine. 2018;71(5):608-17.e15. 4. atabaki p, mehryar hr, aghazadeh j, zeinali m, hasani l, nouri gh. evaluation of attitude of doctors and nurses of emergency department toward presence of patients’ relatives during cardiopulmonary resuscitation in selected emergency department centers in urmia, iran. j anal res clin med. 2018;6(3):115-20. 5. bellali t, manomenidis g, platis c, kourtidou e, galanis p. factors associated with emergency department health professionals’ attitudes toward family presence during adult resuscitation in 9 greek hospitals. dimensions of critical care nursing : dccn. 2020;39(5):269-77. 6. lederman z, baird g, dong c, leong bs, pal ry. attitudes of singapore emergency department staff towards family presence during cardiopulmonary resuscitation. clin ethics. 2017;12(3):124-34. 7. toronto ce, larocco sa. family perception of and experience with family presence during cardiopulmonary resuscitation: an integrative review. j clin nurs. 2019;28(12):32-46. 8. barreto ms, garcia-vivar c, mitchell m, marcon ss. family presence during resuscitation in emergency departments: professionals’ attitudes in brazil. international nursing review. 2018;65(4):567-76. 9. abdar me, rafiei h, amiri m, tajadini m, tavan a, rayani f, et al. iranian nurse attitudes towards the presence of family members during cpr. br j card nurs. 2016;11(9):438-43. 10. hassankhani h, zamanzadeh v, rahmani a, haririan h, porter je. family presence during resuscitation: a double-edged sword. j nurs scholarsh. 2017;49(2):12734. 11. al-mutair as, plummer v, copnell b. family presence during resuscitation: a descriptive study of nurses’ attitudes from two saudi hospitals. nurs crit. 2012;17(2):908. 12. zali m, hassankhani h, powers ka, dadashzadeh a, rajaei ghafouri r. family presence during resuscitation: a descriptive study with iranian nurses and patients’ family members. international emergency nursing. 2017;34:11-6. 13. hassankhani h, zamanzadeh v, rahmani a, haririan h, porter je. family presence during resuscitation: a double-edged sword. j nurs scholarsh. 2017;49(2):12734. 14. leung ny, chow sk. attitudes of healthcare staff and patients’ family members towards family presence during resuscitation in adult critical care units. j clin nurs. 2012;21(13-14):2083-93. 15. mahabir d, sammy i. attitudes of ed staff to the presence of family during cardiopulmonary resuscitation: a trinidad and tobago perspective. emergency medicine journal : emj. 2012;29(10):817-20. 16. sak-dankosky n, andruszkiewicz p, sherwood pr, kvist t. integrative review: nurses’ and physicians’ experiences and attitudes towards inpatient-witnessed resuscitation of an adult patient. journal of advanced nursing. 2014;70(5):957-74. 17. ferrara g, ramponi d, cline tw. evaluation of physicians’ and nurses’ knowledge, attitudes, and compliance with family presence during resuscitation in an emergency department setting after an educational intervention. advanced emergency nursing journal. 2016;38(1):32-42. 18. dabiriyan a hs, majd ha, ezati z. attitudes of physicians and nurses toward family presence during resuscitation in emergency rooms of hospitals affiliated with tehran, iran and shahid beheshti universities of medical sciences. adv nurs midwifery. 2010;20(69):1-4. 19. taraghi z, ilail e, yaghoobi t, noroozinejad f, naseri f, baghernejad sk, et al. a comparison between physicians, nurses and the immediate families of patients‘ attitudes towards family members presence during cpr. hospital. 2013;12(3):65-74. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e58 or i g i n a l re s e a rc h evaluating the ability of prism4 and pim3 to predict mortality in patients admitted to pediatric intensive care unit; a diagnostic accuracy study victoria chegini1, hamidreza hatamabadi2, sima jedari attaran3, abolfazl mahyar3, monirsadat mirzadeh4, venus chegini5∗ 1. department of pediatrics, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of pediatrics, school of medicine, qazvin university of medical sciences, qazvin, iran. 4. department of community medicine, school of medicine, qazvin university of medical sciences, qazvin, iran. 5. department of obstetrics and gynecology, school of medicine, qazvin university of medical sciences, qazvin, iran. received: may2022; accepted: june 2022; published online: 21 july 2022 abstract: introduction: limited resources and the large number of children in need of services in the pediatric intensive care unit (picu) emphasize the need for effective allocation of resources for improving the outcome of at-risk patients. this study aimed to evaluate and compare the accuracy of prism4 and pim3 systems in prediction of in-hospital mortality of patients admitted to picu. methods: the present retrospective cross-sectional study was a diagnostic accuracy study performed on patients admitted to picu of qods hospital, qazvin, iran, during one year. scores of prism4 and pim3 scales were calculated for each patient using the available calculators, and the outcome of patients regarding in-hospital mortality was recorded. finally, screening performance characteristics of the mentioned scales in prediction of patients’ mortality were calculated and reported. results: 218 patients with the mean age of 40.68 ± 37.92 (2-160) months were studied (57.8% female). there was a significant direct correlation between pim3 score and duration of stay in picu (p < 0.0001; r = 0.259), need for inotropic drug administration (p = 0.001), and mortality rate (p = 0.001). in addition, area under the receiver operating characteristic (roc) curve of pim3 and prism4 in prediction of mortality among patients admitted to the picu was 0.939 (95%ci: 0.880 – 0.998) and 0.660 (95%ci: 0.371 – 0.950), respectively (p = 0.001). based on the findings, the best cut-off point for pim3 scale in prediction of mortality was the score of 4 and it was estimated to be the core of 8 for prism4 scale. sensitivity and specificity of pim3 scale in prediction of mortality in the cut-off of 4 points were 100.00 (95% ci: 56.09100.00) and 81.51 (95% ci: 75.4786.38), respectively. these measures were 42.85 (95%ci: 11.8079.76) and 98.10 (95%ci: 94.8999.39) for prism4 model, which indicates the higher sensitivity of pim3 system in this regard. conclusion: based on the results of the present study, the accuracy of pim3 is significantly higher than prism4 in prediction of in-hospital mortality among patients admitted to the picu. it seems that considering the 100% sensitivity of pim3 in prediction of outcome, this model is a better tool for screening patients who are at risk for in-hospital mortality in order to pay more attention and allocate more resources to improve their outcome. keywords: intensive care units, pediatric; mortality; clinical decision rules; prognosis cite this article as: chegini v, hatamabadi h, jedari attaran s, mahyar a, mirzadeh m, chegini v. evaluating the ability of prism4 and pim3 to predict mortality in patients admitted to pediatric intensive care unit; a diagnostic accuracy study. arch acad emerg med. 2022; 10(1): e58. https://doi.org/10.22037/aaem.v10i1.1738. ∗corresponding author: venus chegini; department of obstetrics and gynecology, school of medicine, qazvin university of medical sciences, qazvin, iran. email: venus_chegini@yahoo.com, phone: 00989123815963, orcid: http://orcid.org/0000-0002-8031-5840 . this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. chegini et al. 2 1. introduction among the most important aims in the pediatric intensive care unit (picu) are providing quality care, providing relief for the disease without causing any permanent disabilities and side effects, and reducing the mortality of critically ill children. since the foundation of the first picu in 1955 in sweden, considerable advances have been made in the quality of care provided for the admitted patients, which has led to decrease in mortality rate from 8-18% in previous years to 3-5% (average 2.7%) in recent years (1, 2). this considerable achievement is the result of employing the best human resources and efficient use of the most recent diagnostic and therapeutic technologies. evaluating the quality and efficacy of the measures and assessing the cost-effectiveness of intensive care is very important in efficient ressource allocation among patients (3). a reliable index of the efficiency of the mentioned unit is the standardized mortality ratio (smr). smr is the ratio of mortalities observed in the studied group to the expected mortality in the general public (2). prediction of the risk of mortality and morbidity in patients admitted to the icu is very effective in improving the quality of measures taken and decreasing probable errors and can be of great help in allocating the available resources. in order to estimate the risk of mortality and the prognosis of the patient for allocating resources and evaluating the quality of service, many scoring systems have been introduced to date, among which prism (pediatric risk of mortality) and pim (pediatric index of mortality) are two of the major models used for predicting mortality in the pediatric population (4, 5). prism uses the physiological and laboratory parameters in the first 24 hours of admission and the variables used in pim include clinical and laboratory indices, underlying illnesses or surgical conditions leading to hospital admission. in the studies performed in various population, the results of evaluating the two models for determining which is superior in determining prognosis have been different (5). the study performed by ea ozer et al. in 2004 on 105 babies less than 1year-old in picus of hospitals in turkey showed that pim was a better scale than prism for predicting mortality in countries with a higher rate of mortality and underlying disease (6). meanwhile, in the study by rajia et al. on 50 children in egypt in 2019 showed that both systems had good predictions but prism was a better predictor (7). therefore, the aim of this study was evaluating and comparing prism4 and pim3 systems in predicting in-hospital mortality of patients admitted to picu. 2. methods 2.1. study design and setting the present retrospective cross-sectional study is a diagnostic accuracy study performed on patients admitted to the picu of qods hospital, qazvin, iran, from may 2019 until may 2020. the scores of pim3 and prism4 scales were calculated for each patient using the available calculators and the outcome of patients regarding in-hospital mortality was recorded. finally, the screening performance characteristics of the mentioned scales in prediction of patient outcomes was calculated. the protocol of the study was approved by the ethics committee of qazvin university of medical sciences (ethics code: ir.qums.rec.1399.182). the researchers adhered to the principles of ethics in biomedical research and observed confidentiality of patients’ data throughout the study. 2.2. participants all the patients over 1 month and less than 12 years old, admitted to picu of qods children hospital in qazvin, iran, were included in the study during the mentioned time using census method for sampling. patients with the icu stay of less than 12 hours or mortality within less than 12 hours were excluded from the study. in addition, profiles with missing or incomplete data regarding the required variables were also excluded from the study. it should be noted that the picu of the hospital is managed with a closed system under the supervision of a fellowship of intensive care. 2.3. data gathering demographic and baseline characteristics of patients including age, sex, initial diagnosis, underlying illnesses, duration of hospitalization in the icu, and all clinical and laboratory variables required for calculation of pim3 and prism4 scores, based on their latest versions (8, 9), were extracted from their clinical records and recorded in a designed checklist. in addition, outcomes such as need for mechanical ventilation, need for inotropic drug administration, duration of picu stay, and in-hospital mortality after 12 hours were recorded for all patients. then pim3 and prism4 scores were calculated and recorded for all patients by a senior resident under the supervision of a pediatrician using online calculators and entering the required variables based on the patients’ condition upon admission. pim and prism are two clinical decision rules or scoring systems that have been designed for predicting mortality among patients admitted to picu and have changed during the recent years, the last versions of which are available to researchers and practitioners under the names prism4 and pim3. in a multi-center study published in 2019, which was performed on 10078 patients admitted to picu, prism3 was revised and after undergothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e58 table 1: characteristics of the studied population variable value age (months) 40.68 ± 37.92 gender female 126 (57.8) male 92 (42.2) diagnosis medical 199 (91.3) surgical 19 (8.7) underlying disease immunodeficiency 3 (1.4) malignancy 8 (3.7) cardiovascular disease 16 (7.3) hematologic disease 10 (4.6) endocrine disorders 30 (13.8) renal disease 10 (4.6) musculoskeletal disease 29 (13.3) vital signs temperature (celsius) 37 (36.6 – 37.7) systolic blood pressure(mmhg) 107 (97 – 116) diastolic blood pressure(mmhg) 64 (56 – 75) heart rate (in a minute) 132 (116 – 154) glasgow coma scale 15 (15 – 15 ) outcomes recovered and discharged 203 (93.7) transferred to other hospitals 8 (3.7) dead 7 (3.2) in need of mechanical ventilation 21 (9.6) in need of inotropic drugs 62 (28.4) score prism4 1.6 (0.7 – 3.1) pim3 1.0 (1.0 -1.0) findings are presented as mean ± standard deviation, number (percentage) and median (interquartile range). ing changes for improving the accuracy of predictions and having less percent error it was reintroduced under the name prism4. 2.4. outcomes the main outcome evaluated in the present study was inhospital mortality of patients admitted to picu. in addition, the duration of picu stay and need for inotropic drugs were also studied as secondary outcomes. 2.5. statistical analysis after filling out the checklists, the data were entered to spss software version 23 and analyzed. data are reported as mean ± standard deviation (sd), frequency (%), or median (interquartile range (iqr)). based on the distribution of samples in the population, correlation coefficient, chi square, t-test, or their non-parametric counterparts were used and, in all comparisons, level of significance was considered to be less than 0.05. to calculate the accuracy of the two mentioned systems in evaluation of patients’ outcomes, area under the receiver operating characteristic (roc) curve was used and the screening performance characteristics of the two studied scoring systems in the best cut-off points extracted from the roc curve were calculated with 95% confidence intervals (ci) using vassarstats online calculator and reported. 3. results 3.1. baseline characteristics of the studied patients 218 patients with the mean age of 40.68 ± 37.92 (range: 2-160) months were studied (57.8% female). table 1 shows the baseline characteristics of the studied patients. the most common chief complaints of patients on admission were respiratory problems (29.8%), and eating disorders (17.9%). the most common underlying illnesses among the studied cases were endocrine diseases (13.8%) and musculoskeletal diseases (13.3%). mean duration of picu stay was 5.94 ± 4.97 (range: 1-45) days. median and iqr of prism4 and pim3 scores in the studied patients were 1.6 (0.7 – 3.1) and 1.0 (1.0 -1.0), respectively. the rate of mortality among patients admitted to picu in the present series was estimated to be 3.2% (7 cases). 3.2. evaluating the predictive value of the studied models there was a significant direct correlation between pim3 score and duration of stay in picu (p < 0.0001; r = 0.259), need for inotropic drug administration (p = 0.001), and mortality rate (p = 0.001). however, the correlation between prism4 score and duration of stay in picu (p = 0.697; r = 0.27), need for inotropic drug administration (p = 0.139), and mortality rate (p = 0.107) was not significant. area under the roc curve of pim3 and prism4 in predicting the need for inotropic drugs among patients admitted to picu were 0.659 (95%ci: 0.575 – 0.743) and 0.558 (95%ci: 0.469 – 0.646), respectively (figure 1). based on the findings, the best cut-off point for pim3 scale in prediction of need for inotropic drugs was the score of 4 and for prism4 scale, it was estimated to be the score of 8. in addition, the area under the roc curve of pim3 and prism4 in prediction of the mortality of patients admitted to picu were 0.939 (95%ci: 0.880 – 0.998) and 0.660 (95%ci: 0.371 – 0.950), respectively (figure 1). based on these findings, the best cut-off point for pim3 scale in prediction of mortality was the score of 4 and for prism4 scale, it was estimated to be the score of 8. table 2 shows the screening performance characteristics of the two studied scales in prediction of mortality at their best cut-off points. sensitivity and specificity of pim3 model in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. chegini et al. 4 figure 1: the area under the rock curve of pim3 and prism4 criteria in predicting mortality (a) and the need for inotropic drugs (b) in patients admitted to the pediatric intensive care unit. table 2: screening performance characteristics of pim3 and prism4 scoring systems in predicting the mortality of patients admitted in pediatric intensive care unit character pim3 prism4 tp 7 3 tn 172 207 fp 39 4 fn 0 4 sensitivity 100.00 (56.09100.00) 42.85 (11.8079.76) specificity 81.51 (75.4786.38) 98.10 (94.8999.39) positive predictive value 15.21 (6.8329.48) 42.85 (11.8079.76) negative predictive value 100.00 (97.27100.00) 98.10 (94.8999.39) positive likelihood ratio 0.179 (0.089 – 0.358) 0.75 (0.25 – 2.18) negative likelihood ratio 0 (0 – nan) 0.019 (0.007 – 0.051) data are presented with 95% confidence interval. nan: the calculation cannot be performed because the entered values include one or more instances of zero. prediction of mortality at the cut-off point of 4 were 100.00 (95% ci: 56.09100.00) and 81.51 (95% ci: 75.4786.38), respectively. these measures were 42.85 (95%ci: 11.8079.76) and 98.10 (95%ci: 94.8999.39) for prism4, respectively, which indicates the higher sensitivity of pim3 system for the mentioned purpose. 4. discussion based on the results of the present study, the frequency of inhospital mortality in the studied picu was 3.2% (7 cases out of the 218 cases admitted during one year). the accuracy of pim3 system was significantly higher than prism4 system in the prediction of in-hospital mortality. it seems that pim3 system is a better screening tool for patients at risk of in-hospital mortality considering its 100% sensitivity. unlike prism4, pim3 system has a significant and direct correlation with duration of picu stay as well as the need for inotropic drugs as patients with longer durations of picu stay and those in need of inotropic drugs had higher pim3 scores. in accordance with the present results, a study by lopez (2018) demonstrated that pim can adequately predict the mortality rate in icu patients (10). lee et al. in a study in 2017 showed that pim3 score is a good predictor of the outcome for patients under 18 but not as efficient for hematooncologic patients (11). the performed study by ea ozer et al. in 2004 on 105 babies less than 1-year-old in picus of hospitals in turkey showed that pim system is a better prognostic score than prism to predict mortality in countries with higher mortality rate and high prevalence of pre-existing medical conditions (6). a more recent study on 190 under 18 patients showed that pim is a more accurate predictive score than prism score (12), in contrast to the study by ragia et al. in egypt which stated both of the systems were effective but prism was a better predictor (7). another study performed on 145 picu patients in india observed that prism3 score was associated with higher mortality rate and longer icu stays, but it did not reliably estimate the survival rate, since sometimes patients with a very high prism3 score survived (11). balkin morel et al. studied 14268 patients diagnosed with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e58 pulmonary hypertension in 153 picus in america and concluded that pim2 and prism3 are both efficient scores for early identification and early treatment of high-risk patients and they can be used to update children’s parents on their treatment progress and outcome (13). same results were obtained in gandhi et al ‘s study in 2013. they proved that pim2 can help predict the mortality rate in children and counsel their parents in the earliest stages of disease (14). kadivar et al. declared that prism score measures the disease severity and identifies the triage level of the children who derive greater benefits from picu services (15). these results support the results of costa et al ‘s study in brazil (16). according to the present study it appears that pim3 system by a cut-off point of 4 is an accurate tool to help predict the likelihood of mortality and triage level of patients who are at lower risk. our study suggests that sensitivity and specificity of this version of pim enabled this scoring system as an effective clinical decision-making tool, because it can determine which patients actually need icu admission and benefit the most from treatment in an intensive care unit. meanwhile prism score had a greater specificity but very low sensitivity and this means prism score has a low positive predictive value for screening and predicting the outcome in the present study. on the other hand, the variables of pim system require less laboratory testing, meaning it may be a faster and more efficient system to use. in our study prism system lacked the efficiency to predict the prognosis of picu patients. this matter could be due to prevalence of pre-existing conditions and different types of medical conditions leading to hospital admission. there is therefore a definite need for multi-center studies with bigger sample sizes to settle this claim. overall, clinical decision-making system is improving day by day to increase the quality of care and it seems that the future of clinical decision-making could be highly dependent on these scoring systems to enhance the patient’s outcomes. 5. limitations these findings are limited by the use of retrospective design because as we mentioned earlier profiles with missing or incomplete data regarding the required variables were excluded from the study. further studies with bigger sample sizes may help validate these results. 6. conclusion based on the findings of present study pim3 is significantly more accurate in predicting the in-hospital death of picu patients than prism4 .it seems that considering the 100% sensitivity of pim3 system in prediction of outcome, this model is a better screening tool for patients at risk of in-hospital mortality that actually need icu admission and specialized care or need to be transported to a more equipped hospital and also allocate more resources to them to prevent their death and improve their outcome. 7. declarations 7.1. acknowledgments we would like to express our appreciation to the icu staff in qods hospital in qazvin for their valuable effort during the conduction of the study. 7.2. authors’ contributions vic: devised the study, the main conceptual ideas and proof outline. hh and am: technical details, overall direction and planning sja and vec: data gathering and calculating the scores msm: analysis and interpretation of the data all authors read, discussed the results, commented on, and approved the final version of manuscript. 7.3. funding and supports this study is not funded. 7.4. conflict of interest the authors declare no conflicts of interest in this study. references 1. taori rn, lahiri kr, tullu ms. performance of prism (pediatric risk of mortality) score and pim (pediatric index of mortality) score in a tertiary care pediatric icu. the indian journal of pediatrics. 2010;77(3):267-71. 2. qiu j, lu x, wang k, zhu y, zuo c, xiao z. comparison of the pediatric risk of mortality, pediatric index of mortality, and pediatric index of mortality 2 models in a pediatric intensive care unit in china: a validation study. medicine. 2017;96(14). 3. verlaat cw, wubben n, visser ih, hazelzet ja, van der hoeven j, lemson j, et al. retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the netherlands. bmc pediatrics. 2019;19(1):1-6. 4. shann f, pearson g, slater a, wilkinson k. paediatric index of mortality (pim): a mortality prediction model for children in intensive care. intensive care medicine. 1997;23(2):201-7. 5. pollack mm, ruttimann ue, getson pr. pediatric risk of mortality (prism) score. critical care medicine. 1988;16(11):1110-6. 6. ozer ea, kizilgunesler a, sarioglu b, halicioglu o, sutcuoglu s, yaprak i. the comparison of prism and pim this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. chegini et al. 6 scoring systems for mortality risk in infantile intensive care. journal of tropical pediatrics. 2004;50(6):334-8. 7. yousef ra, el gendy fm, abd el aziz aa. prognostic scoring systems in pediatric icus: pediatric risk of mortality iii versus pediatric index of mortality 2. alexandria journal of pediatrics. 2019;32(1):27. 8. pollack mm, holubkov r, funai t, dean jm, berger jt, wessel dl, et al. the pediatric risk of mortality score: update 2015*. pediatric critical care medicine. 2016;17(1):2-9. 9. straney l, clements a, parslow rc, pearson g, shann f, alexander j, et al. paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care. pediatric critical care medicine. 2013;14(7):67381. 10. lópez mdpa, boada n, fernández a, fernández al, ratto me, serrate as, et al. performance of the pediatric index of mortality 3 score in picus in argentina: a prospective, national multicenter study. pediatric critical care medicine. 2018;19(12):e653. 11. lee oj, jung m, kim m, yang h-k, cho j. validation of the pediatric index of mortality 3 in a single pediatric intensive care unit in korea. journal of korean medical science. 2017;32(2):365-70. 12. ramazani j, hosseini m. comparison of the predictive ability of the pediatric risk of mortality iii, pediatric index of mortality3, and pediatric logistic organ dysfunction-2 in medical and surgical intensive care units. journal of comprehensive pediatrics. 2019;10(2). 13. balkin em, steurer ma, delagnes ea, zinter ms, rajagopal s, keller rl, et al. multicenter mortality and morbidity associated with pulmonary hypertension in the pediatric intensive care unit. pulmonary circulation. 2018;8(1):1-11. 14. gandhi j, sangareddi s, varadarajan p, suresh s. pediatric index of mortality 2 score as an outcome predictor in pediatric intensive care unit in india. indian journal of critical care medicine: peer-reviewed, official publication of indian society of critical care medicine. 2013;17(5):288. 15. kadivar m, nourbakhsh s, nouri k, samadi kp. evaluating pediatric risk of mortality (prism) score in a pediatric critical setting: a prospective observational study in children’s medical center. 2001. 16. costa ga, delgado af, ferraro a, okay ts. application of the pediatric risk of mortality (prism) score and determination of mortality risk factors in a tertiary pediatric intensive care unit. clinics. 2010;65:1087-92. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e38 or i g i n a l re s e a rc h nurses’ knowledge regarding oxygen therapy; a crosssectional study maryam hassanzad1, hosseinali ghaffaripour1, mahsa rekabi1, mahsa mirzendehdel1, elham sadati1, nasrin elahimehr1, hojjat derakhshanfar1∗ 1. pediatric respiratory disease research center, nritld, masih daneshvari hospital, shahid beheshti university of medical sciences, tehran, iran. received: march 2021; accepted: april 2021; published online: 18 may 2022 abstract: introduction: oxygen therapy, if done correctly, can save patients’ life promptly. however, improper use will be just as dangerous. the present study aimed to investigate the level of nurses’ knowledge on properly using oxygen. methods: this was a cross-sectional study with a minimum sample size of 72 nurses who were randomly selected from various wards of masih daneshvari hospital, tehran, iran. to determine the level of knowledge about oxygen therapy, a questionnaire was used to collect data. this questionnaire consists of seven items, each of which is designed to determine the level of the individual’s knowledge about the various details of oxygen therapy. results: seventy-eight nurses with the mean age of 35.80±7.42 years participated in the study (87% female). the mean knowledge score of nurses regarding oxygen therapy was 8.89 ± 2.79 out of 16 points. 84.6% of the nurses were able to differentiate various types of oxygen masks. accordingly, 94.9% of nurses had good knowledge on oxygen humidification. also, 50% of the nurses had sufficient knowledge about the amount of oxygen flow produced by different masks. 10.3% of the nurses could choose the most appropriate mask for different clinical conditions. 6.4% of the nurses had knowledge of working with flowmeters, and 15.4% of the nurses had sufficient information about the maximum level of oxygen required for the patient. 17.9% of the nurses were familiar with measuring the appropriate amount of oxygen for patients. there was no statistically significant relationship between age (p = 0.57), gender (p = 0.09), employment status (p = 0.38), workplace (p = 0.86), current position (p = 0.11), degree (p = 0.27), and graduation time (p = 0.58) of nurses with good knowledge of using oxygen. however, a statistically significant relationship was reported between nurses’ related work experience and their knowledge of the proper use of oxygen (p = 0.03). conclusion: in general, the nurses’ knowledge at masih daneshvari hospital on how to properly use oxygen is at a moderate level. nurses’ knowledge in some areas, such as working with the flowmeter, choosing the suitable mask for specific clinical conditions, and the maximum oxygen required for patients, is meager and requires training intervention. keywords: oxygen inhalation therapy; nurses; knowledge cite this article as: hassanzad m, ghaffaripour h, rekabi m, mirzendehdel m, sadati e, elahimehr n, derakhshanfar h. nurses’ knowledge regarding oxygen therapy; a cross-sectional study. arch acad emerg med. 2022; 10(1): e38. https://doi.org/10.22037/aaem.v10i1.1553. 1. introduction oxygen is an essential element of life. however, it can have both extraordinary biological benefits and acute toxic effects, like medicine. in addition, the world health organization has introduced oxygen as one of the essential medical items required in the health system (1). supplemental oxygen therapy (sot) is a treatment that plays a vital role in preventing and managing tissue hypoxemia in patients with acute ∗corresponding author: hojjat derakhshanfar; mofid children’s hospital, shariati ave, tehran, iran. tel: +982122227033, email: hojjatderakhshanfar@gmail.com, orcid: https://orcid.org/0000-0002-9114-7491. and chronic problems (2,3). this method, if used correctly, can improve treatment outcomes and save the patient’s life; however, improper use can be extremely harmful (4). according to the british thoracic society guidelines, the indicator of proper oxygen therapy is to achieve normal or nearnormal oxygen levels of inpatients in the intensive care unit (icu) or emergency (5). the amount and method of delivering oxygen to the patient depend on the underlying condition and whether the patient’s condition is acute or chronic. the choice of device and the right amount of oxygen depends on many factors, such as the patient’s age, the doctor’s treatment goals, and patient’s tolerance (6,7). oxygen should be administered to achieve a 94-98% saturation level for most patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hassanzad et al. 2 with acute conditions or 88-92% for patients at risk of respiratory failure (8). breathing oxygen at a concentration more than 50% can poison the patient after 24 hours (9). the central nervous system, the respiratory system (especially the lungs), and the eyes are the organs that are primarily affected by the improper use of oxygen. given that there is no treatment that can reverse toxic pulmonary changes, the only logical way is to prevent oxygen-induced poisoning (10). for this reason, it is essential to employ experienced staff to use oxygen, and monitor arterial blood gases and pulse oximetry of the patient. in most medical centers, nurses are responsible for oxygen therapy and immediate response to the undesirable therapyinduced effects (11). based on studies conducted in different countries, in most cases, there is a significant knowledge gap in nurses’ knowledge about how to use oxygen properly (12–14). for example, studies in ethiopia indicated that only one-third of nurses had the practical knowledge to use oxygen (15). another study in turkey found that nurses over 45 or those with more than 14 years of experience in the ward and nurses in the surgical ward were significantly less likely to use oxygen properly (16). studies conducted in saudi arabia also showed a lack of proper knowledge among nurses about oxygen therapy. according to the results, high workload and lack of local guidelines were the fundamental causes (12). studies conducted in uganda have also shown that all nurses need training in this area (17). the present study aimed to investigate the knowledge of nurses working in an educational hospital on the correct use of oxygen for therapy. 2. method 2.1. study design and setting in this cross-sectional study, nurses were consecutively enrolled from different wards of masih daneshvari hospital, tehran, iran, from october to december 2021. the nurses’ knowledge about various aspects of oxygen therapy was investigated using a predesigned and validated questionnaire. prior to implementation, the study protocol was discussed in the research ethics committee of shahid beheshti university of medical sciences and approved with the code of ethics number ir.sbmu.msp.rec.1399.565. 2.2. participants all nurses working in masih daneshvari hospital were included without sampling. the inclusion criterion was working as a nurse in one of the hospital’s clinical wards. nurses who did not want to participate in the study and fill out the questionnaire were excluded from the study. table 1: baseline characteristics of studied cases variables values age (year) 35.80 ± 7.42 gender male 10 (13) female 68 (87) academic degree bachelor’s 73 (93.6) master’s 5 (6.4) employment status contractual 15 (19.2) permanent 49 (62.8) compulsory medical service program 12 (15.4) temporary 2 (2.6) workplace icu emergency 6 (7.7) icu internal 7 (9.0) emergency 3 (3.8) internal ward 12 (15.4) pediatric ward 5 (6.4) oncology 5 (6.4) surgery 16 (20.5) icu surgery 5 (6.4) ccu 12 (15.4) bronchoscopy 2 (2.6) infectious diseases emergency 5 (6.4) current position nurse 67 (86) nursing assistant 4 (5) supervisor (matron) 7 (9) graduation time (year) 11.28 ± 7.77 work experience in masih daneshvari hospital less than eight months 17 (21.8) 8-16 months 40 (51.2) more than 16 months 21 (27) relevant work experience less than eight years 29 (37.2) 8-16 years 28 (35.8) more than 16 years 21 (73) relevant educational experience yes 46 (59) no 32 (41) data are presented as mean ± standard deviation (sd) and frequency (%) icu: intensive care unit; ccu: critical care unit. 2.3. data gathering the questionnaire previously used in the study by cinar et al. (18), which comprised seven questions and each question was designed to determine the individual’s knowledge level about the various aspects of oxygen therapy, was used for data gathering. the questionnaire was translated into the persian language. specialists confirmed its validity, and its reliability of was verified by conducting a pilot study (on 20 nurses outside of the sample, α=0.7). after distributing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e38 table 2: frequency distribution of correct answers given by nurses to the questionnaire questions value q1. identifying the types of oxygen masks a 69 (88.5) b 73 (93.6) c 69 (88.5) d 71 (91.0) q2: the amount of oxygen flow produced by different masks a 39 (50.0) b 41 (52.6) c 62 (79.5) d 63 (80.8) q3: how to choose the most suitable mask for different clinical conditions a 18 (23.1) b 17 (21.8) c 35 (44.9) d 32 (41.0) q4: how to measure the suitable amount of oxygen for the patient 14 (17.9) q5: how to work with a flowmeter 5 (6.4) q6: maximum oxygen level required for the patient 12 (15.4) q7: oxygen humidification 74 (94.9) data are presented as number (%). the questionnaire among the nurses, they were asked to answer the questions within 20 minutes. for each correct answer to the questions, a score of one, and for each incorrect answer, a score of zero was considered. given that the first three questions consisted of four sections, the possible scores ranged from zero to 16. questionnaires were completed anonymously. the first part of the questionnaire includes demographic information and details about the degree, graduation time, employment status, work experience in masih daneshvari hospital, related work experience, workplace in the hospital, current position, and history of attending oxygen therapy course. 2.4. statistical analysis after the questionnaires were filled out, the data were entered into spss software version 23 and analyzed. mean and standard deviation were used to describe qualitative variables, and frequency to describe quantitative variables. one-way analysis of variance was used to investigate the relationship between nurses’ level of knowledge on how to use oxygen and independent study variables. the significance level of the calculations was considered 0.05. 3. results 3.1. baseline characteristics of studied nurses a total of 78 nurses with a mean age of 35.80±7.42 years participated in the study (87% female). most of the nurses in the study had a bachelor’s degree (93.6%) and were permanently employed (62.8%). most nurses’ work experience was between 8 and 16 months (51.2%), and 59% of nurses had previously received oxygen therapy training. table 1 shows more details about the baseline characteristics of the studied nurses. 3.2. knowledge of the studied nurses regarding o2 therapy reviewing the nurses’ answers to the questions showed that none of the nurses could answer all the questions correctly. details of the correct answers provided to the questions are shown in table 2. the overall mean score obtained from the questionnaire was 8.89± 2.79. there was no statistically significant relationship between age (p = 0.57), gender (p = 0.09), employment status (p = 0.68), workplace (p = 0.86), current position (p = 0.11), degree (p = 0.27), and graduation time of nurses (p = 0.58) and their knowledge of using oxygen properly. besides, there was no statistically significant relationship between nurses’ work experience in masih daneshvari hospital and the history of oxygen therapy training courses with their knowledge of properly using oxygen (p = 0.15). however, there was a statistically significant relationship between nurses’ relevant work experience and their knowledge of properly using oxygen (table 3). 4. discussion according to the results of the present study, the mean score obtained by nurses from the questionnaire to determine the level of knowledge of oxygen therapy was 8.89± 2.79. given that the maximum score is 16, it can be said that most nurses had a moderate knowledge of properly using oxygen. the obtained results were consistent with similar studies in other parts of the world. for example, in zeleke and kefale’s study, only one-third of the nurses had relevant practical knowledge of the proper use of oxygen (15). in demirel and kazan’s study, the nurses’ knowledge of oxygen therapy was much lower than expected (16). in addition, the results of the present study, along with other studies, indicate that nurses do not receive adequate training on how to properly work with oxygen. however, more detailed studies on each of the questionnaire areas indicate that in some areas, nurses have a relatively good level of knowledge; in contrast, in some areas they are severely weak. for example, in the present study, 84.6% of the nurses were able to differentiate between various types of oxygen masks. however, in the study of demirel this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hassanzad et al. 4 table 3: investigating the relationship between independent research variables and nurses’ knowledge about oxygen therapy variables values p-value age (year) less than 30 9.3±04.24 30-40 8.2±63.85 0.57 more than 40 8.2±91.33 gender male 8.2±94.64 0.09 female 7.4±57.28 academic degree bachelor’s 8.2±81.82 0.27 master’s 9.2±80.77 employment status contractual 8.3±07.93 permanent 9.2±10.36 0.38 compulsory medical service program 9.3±00.13 temporary 10.0±50.71 workplace icu emergency 7.2±67.66 icu internal 7.3±43.74 emergency 10.0±67.58 internal ward 9.2±33.50 pediatric ward 9.2±60.07 oncology 9.2±00.55 0.86 surgery 8.2±50.75 icu surgery 10.1±00.87 ccu 10.0±50.76 bronchoscopy 7.2±50.12 infectious diseases emergency 9.2±60.19 current position nurse 9.2±43.21 nursing assistant 11.0±50.71 0.11 supervisor (matron) 8.2±00.83 graduation time less than ten years 8.3±25.26 10-20 years 9.2±30.45 0.58 more than 20 years 9.2±22.33 work experience less than eight months 9.2±12.83 8-16 months 9.2±23.38 0.15 more than 16 months 8.2±67.64 relevant work experience less than eight years 8.3±79.28 8-16 years 9.1±55.99 0.03 more than 16 years 8.2±80.40 relevant educational experience yes 9.2±20.45 0.38 no 8.3±36.3 data are presented as mean ± standard deviation (sd). icu: intensive care unit; ccu: critical care unit. and kazan (16) and cinar et al. (18), nurses’ knowledge about recognizing different types of masks was less than in the present study. the cause can be the type of hospitals studied. in addition, nurses working in public hospitals were evaluated in the two mentioned studies. many oxygenation methods and masks are not used in these hospitals, so the lower level of nurses’ knowledge about the type of masks is not surprising. however, masih daneshvari hospital is a specialized hospital for respiratory diseases, for this reason, different types of oxygenation methods are used in the clinics of this hospital. therefore, it seems logical that the knowledge of this hospital’s nurses regarding the types of masks and oxygenation methods is higher than other hospitals. another area in which the nurses’ knowledge was at a dethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e38 sirable level is oxygen humidification. oxygen can easily remove humidity from the upper respiratory tract membrane. proper oxygen humidification can stimulate secretions in the upper respiratory tract membrane and make the patient comfortable (19). therefore, nurses’ knowledge of oxygen humidification is vital in the oxygen therapy process. in the present study, most nurses (94.9%) had the correct knowledge of oxygen humidification. in the studies of arsalan et al. (20) and demirel and kazan (16), more than 95% of nurses answered the question about the knowledge of oxygen humidification correctly. however, this is not far from the expectation because oxygen humidification is among the primary information provided in nursing education. according to obtained results, only 50% of the nurses had sufficient knowledge about the amount of oxygen flow produced by different masks. in other areas of the questionnaire, nurses’ knowledge was much lower. therefore, only 10.3% of the nurses could choose the most appropriate mask for different clinical conditions. similarly, only 6.4% of the nurses knew how to work with a flowmeter, and only 15.4% of them had sufficient knowledge about the maximum level of oxygen needed by the patient. the lack of’ correct answers to the questions presented in the mentioned areas indicates the lack of nurses’ knowledge in these areas. the latest report from the national health system (nhs) on oxygen safety suggests that the main concern about oxygen safety includes determining the amount of oxygen a patient needs (21). given that excessive or insufficient oxygen administration can significantly affect patient health and treatment outcomes, the desired level of nurses’ knowledge in this area will be of great importance. however, in the present study, only 17.9% of nurses were familiar with measuring the appropriate amount of oxygen for patients. in general, none of the nurses were able to answer all the questions correctly. this rate was significantly lower than the rate reported in a similar study conducted by cinar et al. in turkey. in this study, despite most nurses’ low knowledge about the correct way of oxygen therapy, 9% of nurses correctly answered all the questions (18). based on the present study’s results, having relevant work experience had a significant relationship with nurses’ knowledge. nurses who had between 8 and 16 years of relevant work experience were more knowledgeable about oxygen therapy. however, nurses with more than 16 years of experience had a lower average level of knowledge than nurses with 8 to 16 years of experience. age also seems to be an influential factor in nurses’ knowledge of how to appropriately work with oxygen, because in younger nurses (less than 30 years), the average score was higher than other nurses. however, the observed difference was not statistically significant. in demirel and kazan’s (16) research, nurses older than 45 years had obtained significantly lower scores. the significance of the relationship in the study of demirel and kazan may be due to the higher volume of samples studied. in the current study, the average score obtained by nurses with a master’s degrees was also higher than nurses with a bachelor’s degree. however, this difference was not statistically significant. similarly, there was no statistically significant relationship between nurses’ gender and their average score. in demirel and kazan’s study (16), there was no statistically significant relationship between nurses’ degree and gender with their level of knowledge of oxygen therapy. there was no statistically significant relationship between nurses’ employment status, current position, length of nurses’ experience in this hospital, and nurses’ graduation time with their level of knowledge on properly using oxygen. among the nurses working in different hospital wards, the nurses in the emergency ward scored higher than the nurses in other wards. however, this difference was not statistically significant. one of the practical factors in nurses’ ability to perform their tasks and provide proper care is complete mastery in that functional area. training programs and regular retraining on the proper use of oxygen can help build mastery in nurses. some other measures may also help improve the condition. educational posters, information through various information channels about the effects, role, and risks of oxygen therapy, and the development of standard guidelines for the practical guidance of nurses are some of the suggested measures that can affect the level of nurses’ knowledge on properly using oxygen. 5. limitations this study had some limitations. first, the present study only examined the nurses working in masih daneshvari hospital. therefore, the generalization of the results to the nurses of other hospitals in the country should be made cautiously. also, due to the small sample size, the interpretation of relationships between variables should be made with caution. in order to accurately identify the factors affecting nurses’ knowledge about oxygen therapy, it is suggested that a multicenter study be conducted. 6. conclusion according to the present study’s results, in general, the nurses of masih daneshvari hospital have a moderate knowledge of properly using oxygen. in some areas, such as working with flowmeters, choosing the suitable mask for specific clinical conditions, and the maximum oxygen required for patients, nurses’ knowledge is deficient and requires educational intervention. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. hassanzad et al. 6 7. declarations 7.1. acknowledgments we gratefully thank our pediatric respiratory disease research center colleagues for their valuable comments. 7.2. author contribution study design: hojjat derakhshanfar, maryam hassanzad data collection: hosseinali ghaffaripour, mahsa rekabi data analysis: mahsa mirzendehdel, elham sadati manuscript writing: hojjat derakhshanfar, maryam hassanzad, nasrin elahimehr 7.3. funding and support there was no funding or support received for this study. 7.4. conflict of interest there is no conflict of interest for the authors. references 1. world health organization. essential medicines and health products: who model lists of essential medicines. new york: who; 2016. 33–47 p. 2. 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s, ak b, muslu gk. neonatal intensive care nurses’ opinion on oxygen therapy: a survey conducted in turkey. j contemp med. 2017;7(2):184–92. 21. national health service. rapid response report npsa/2009/rrr006: oxygen safety in hospitals. 2009. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e53 rev i ew art i c l e covid-19 vaccines’ protection over time and the need for booster doses; a systematic review omid dadras1,2, seyedahmad seyedalinaghi1, amirali karimi3, alireza shojaei1, ava amiri1, sara mahdiabadi3, amirata fakhfouri4, armin razi3, hengameh mojdeganlou5, paniz mojdeganlou6, alireza barzegary4, zahra pashaei1, amir masoud afsahi7, parnian shobeiri3, esmaeil mehraeen8∗ 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. school of public health, walailak university, nakhon si thammarat, thailand. 3. school of medicine, tehran university of medical sciences, tehran, iran. 4. school of medicine, islamic azad university, tehran, iran. 5. department of pathology, urmia university of medical sciences,urmia, iran. 6. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 7. department of radiology, school of medicine, university of california, san diego (ucsd), california, usa. 8. department of health information technology, khalkhal university of medical sciences, khalkhal, iran. received: march 2022; accepted: may 2022; published online: 4 july2022 abstract: introduction: controversies existed regarding the duration of covid-19 vaccines’ protection and whether receiving the usual vaccine doses would be sufficient for long-term immunity. therefore, we aimed to systematically review the studies regarding the covid-19 vaccines’ protection three months after getting fully vaccinated and assess the need for vaccine booster doses. methods: the relevant literature was searched using a combination of keywords on the online databases of pubmed, scopus, web of science, and cochrane on september 17th, 2021. the records were downloaded and the duplicates were removed. then, the records were evaluated in a two-step process, consisting of title/abstract and full-text screening processes, and the eligible records were selected for the qualitative synthesis. we only included original studies that evaluated the efficacy and immunity of covid-19 vaccines three months after full vaccination.this review adhered to the preferred reporting items for systematic reviews and meta-analyses (prisma) statement to ensure the reliability of results. results: out of the 797 retrieved records, 12 studies were included, 10 on mrna-based vaccines and two on inactivated vaccines. the majority of included studies observed acceptable antibody titers in most of the participants even after 6 months; however,it appeared that the titers could also decrease in a considerable portion of people. due to the reduction in antibody titers and vaccine protection, several studies suggested administering the booster dose, especially for older patients and those with underlying conditions, such as patients with immunodeficiencies. conclusion: studies indicated that vaccine immunity decreases over time, making people more susceptible to contracting the disease. besides, new variants are emerging, and the omicron variant is continuing to spread and escape from the immune system, indicating the importance of a booster dose. keywords: covid-19;covid-19 vaccines; immunity; sars-cov-2; vaccines; vaccine-preventable diseases cite this article as: dadras o, seyedalinaghi sa, karimi a, shojaei a, et al. covid-19 vaccines’ protection over time and the need for booster doses; a systematic review. arch acad emerg med. 2022; 10(1): e53. https://doi.org/10.22037/aaem.v10i1.1582. ∗corresponding author: esmaeil mehraeen, department of health information technology, khalkhal university of medical sciences, khalkhal, iran. postal code: 5681761351, tel: +98-45-32426801, fax: +98-45-32422305, email:es.mehraeen@gmail.com, orcid: http://orcid.org/0000-0003-4108-2973. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 2 1. introduction since the coronavirus disease 2019 (covid-19) pandemic spread all over the globe, it has been posing a considerable healthcare crisis by affecting more than 250 million individuals and leading to more than 5 million deaths up until now (1). it has also influenced other aspects of life, including economic, technological, and social aspects. since covid-19 is highly contagious,substantial effort is required to curtail the pandemic(2). in this regard, vaccines offer a promising opportunity for fighting the pandemic and have shown considerable efficacy against severe covid-19 infection, hospitalization, and death (3). despite the emergence of new variants, the most effective approach to curb the pandemic seems to be mass vaccination and reaching herd immunity against severe acute respiratory syndrome coronavirus 2 (sars-cov-2)(4). the duration of immunity that most vaccines generate against various common infections is limited and developing strong immunity often requires booster doses. the generation of long-term immunity by covid-19 vaccines and the necessity to administer booster doses for different covid19 vaccines is still a matter of debate. considering this, it is of great importance to define the duration in which the humoral immune responses are efficient enough against covid-19 infection (3, 5). some studies have demonstrated that a few months after the injection of the second dose, the effectiveness of covid-19 vaccines wanes as antibody levels drop (6, 7). thus, an additional booster dose may be needed to restore the high level of immunity, especially against new variants, and maintain the equilibrium of the protective humoral immunity and covid19 viral load during exposure. some groups, including the elderly, are at higher risk of profound igg decrease over time and thus increased probability of being infected with covid19(8). however, it is intriguing that even after a few months, the effectiveness against severe disease course and hospitalization is rather sustained (6). in a retrospective cohort study conducted by tartof et al., participants who were fully vaccinated showed high immunity against all variants of covid19 up until six months after vaccination, but the immunity had been decreasing over that time (6). however, they reported no decreased effectiveness against hospital admissions in any age group during the study period. thomas et al. found 91% protection from pfizer/biontech vaccine after six months, silencing the concerns and showing its sufficient protection during this time (9). on september 17th, 2021, the united states food and drug administration (fda) refuted the need for a booster dose six months after the second dose of the pfizer/biontech vaccine for the general population, and only recommended it for people above 65 years of age and some specific groups, but later booster doses were recommended for all the people (10, 11). concerns still exist regarding vaccines’ duration of immunity and the need for booster doses, especially for other types of vaccines (12). considering that new variants of covid-19 may continue to emerge all around the world and disrupt the efforts that have been done so far to control the pandemic, it is of great importance to determine which vaccines require a booster dose for maintaining immunity against covid-19. a systematic evaluation of this matter elucidates the path for designing new vaccination strategies. therefore, we aimed to systematically review the studies regarding the covid-19 vaccines’ protection three or more months after getting fully vaccinated and assess if vaccine booster doses are required. 2. methods this study is a comprehensive review of the literature to describe covid-19 vaccines’ protection over time. we also investigated the need for booster doses. in order to ensure solidity and reliability of the outcomes, this review adhered to the preferred reporting items for systematic reviews and meta-analyses (prisma) statement. 2.1. data sources we executed a comprehensive and systematic search in the online databases of pubmed, scopus, web of science, and cochrane on september 17th, 2021. keywords were selected using the medical subject headings (mesh) and previous studies. we provided the search terms for all the databases in supplementary material 1. the search terms for pubmed were as follows: a. “covid-19” or “sars-cov-2” or “sars-cov2” or “2019ncov” or “novel coronavirus” [title/ abstract] b. “vaccine” or “vaccination” or “vaccinated” or “immunization” [title/ abstract] c. “immunity duration” or “immunity period” or “protection duration” or “duration”or“month” or “year”[title/ abstract] d. [a] and [b] and [c] 2.2. study selection the retrieved records were imported to an endnote file and the duplicates were removed. in a biphasic approach, threeindependent researchers screened and selected eligible studies. inthe first phase, the retrieved records were reviewed and screened based on the relevancy of titles and abstracts. the full texts of the remaining articles were assessed based on eligibility criteria in the second phase to select the most appropriate articles. original articles discussing the efficacy of covid-19 vaccines at least three months after full vaccination (second dose in most cases, first dose in case of singledose vaccines) were included in our study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e53 publications subject to one or more of the following exclusion criteria were excluded from our study: – non-original studies, such as review articles – case reports and case series – abstract papers, conference abstracts, and other studies without available full texts – ongoing clinical trials without yet published results – preclinical studies and studies on subjectsother than humans, such as pure laboratory or animal studies – studies evaluating vaccine effectiveness in periods shorter than three months after becoming fully vaccinated against covid-19. three months was chosen as the cut-off point because full vaccinations usually provide adequate protection in the first three months (13-15). 2.3. data extraction two researchers extracted the following information from the eligible studies included in the review (each recorded the data of half of the studies):first author (reference) id, country and year of study,type of study, study population, sex percentage and mean age of the population, vaccine type, time passing from vaccination,changes in antibody levels, vaccine efficacy against infection, and disease severity parameters as well as mortality, authors’ opinion about booster dose, and summary of other notable findings. these data were transferred into a word table, and then another independent researcher reviewed the extracted results to re-check and verify them. 2.4. quality/risk of bias assessment we utilized the newcastle-ottawa scale (nos) risk assessment tool to evaluate bias risk of the included studies. this scale adds up to a total score of nine in three categories. these categories consist of selection, comparability, and exposure/outcome and receive maximum scores of four, two, and three, respectively (table 2). 3. results in this study, by applying systematic search strategies, 797 relevant records were identified and retrieved from pubmed, scopus, web of science, and cochrane. after a primary review of retrieved articles, 380 duplicates were removed, and the title and abstract of the remaining 417 articles were evaluated. by applying the selection criteria, 388 articles were excluded, and only 29 articles were screened by their full texts. after the review of full texts, 17 articles were excluded. finally, 12 articles met the inclusion criteria and were included in the final review (figure 1). table 1 summarizes the results of the studies. the studies were conducted in various countries with 15 countries involved overall; one study was multinational and included six countries (usa, turkey, germany, south africa, brazil, and argentina), and the other studies were conducted in belgium (n=2), usa, china, estonia, france, spain, israel, greece, italy, and kazakhstan (each n=1).the vaccine types in included studies were mrna-based (n=10), and inactivated virus (n=2)vaccines. the interval between the administration of the second dose of the vaccine and the antibody titer assessment varied between 4 weeks to 6 months. the majority of included studies observed acceptable antibody titers in most of the participants even after 6 months (16, 17); however, the titers decreased in a considerable portion of the people(18). due to the reduction in the antibody titer over time, several studies suggested administering the booster dose, especially for older patients and those with underlying conditions, such as patients with immunodeficiencies(1719).table 2 demonstrates the results of the quality assessment. all the studies had acceptable quality assessment scores, but they mostly lacked adequate matching for confounders. 4. discussion covid-19 pandemic is a serious global challenge due to its high prevalence and the emergence of new variants.vaccination is one of the best solutions to mitigate the immense burden of the virus, in addition to the social distancing, using face masks, and observing health protocols.we reviewed 12 articles concerning covid-19 vaccination, elicited antibody response, duration of triggered immunity, and the necessity of the booster dose. in 10 studies, the vaccine type was mrna-based, and in two studies, it was inactivated vaccine. in seven studies, participants were healthcare workers, adults, and individuals with cancer. the majority of articles mainly discussed the importance of booster doses, since antibody titers decline over time. favresse et al. reported that antibody titers significantly decreased three months after vaccination with bnt162b2 in seronegative and seropositive healthcare workers (20).consistently, the study by erice et al. showed a reduction in anti-sars-cov-2 receptor-binding domain antibody (antirbd antibody) titers in healthy individuals three months after the second dose; indicating that a booster dose could be beneficial(19).terpos et al. also reported a decline in effective antibody titers (anti-s-rbd antibody and neutralizing antibody) six months after vaccination(18). these findings emphasize the beneficial effects of a booster dose against covid-19; particularly, in reducing the rate of hospitalization and mortality, which are specifically important in the elderly and people with underlying diseases. a study by gou et al. on efficacy of inactivated vaccines evaluated 2 age groups, one of which mostly consisted of the elderly. this study demonstrated the value of a booster dose, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 4 as there is always concern over elderly people’s morbidity and mortality (21),yet more studies are required in order to assess the antibody alteration in elderly population. in addition, a study by waldhorn et al. showed a significant decrease in antibody titer over time. since the study population was cancer patients with an average age of 66, it is possible that immunodeficiency and advanced age are both to blame for the considerable drop (22). however, more studies for assessment of antibody alterations in each group, separately, could be useful in determining the effect of each change in factor on antibody titer over time. in recent months,the covid-19 wave attracted global attention due to its new variant (omicron b.1.1.529). although this new variant has lower mortality, it is more contagious, spreads faster, and can even result in severe illness. this global issue could be best resolved by the enhancement of the immune system; therefore, the third dose of vaccine is beneficial to accentuate antibody response(23). concerning the immune response, hedges et al. found that vaccination causes higher levels of antibody in comparison with previous covid-19 infection. this showed the necessity of vaccination even in individuals with previous covid19 infection(24). besides, it has been shown that a booster dose of the covid-19 vaccine can elicit a strong antibody response that could protect the individuals from acquiring the disease and severe disease, and subsequently reduce the mortality and morbidity of the disease (11). studies suggest that age plays an important role in vaccination. the study of naaber et al. reported that older people may have a weaker response to covid-19 vaccines and also may have fewer side effects (16). terpos et al. also showed that antibody titers decrease more slowly in younger persons; therefore, younger individuals had higher antibody titers compared to older people with the same number of days passing from vaccination (18). likewise, erice et al. observed that younger individuals (especially those aged 21 to 30) had higher antibody titers following covid-19 vaccination(19). compared to other included studies, zakaria et al. evaluated the younger study population (mean age: 28) and discovered that antibody titer decreased over time (25). considering this finding and based on the study by terpos et al. (18), booster doses continue to play an important role. terpos et al. also showed that underlying diseases such as diabetes or autoimmune diseases may affect the antibody titers, leading to lower neutralizing antibody titers(18). these findings showed that the efficacy of vaccines can be influenced by different factors, including age and underlying disease. therefore, a booster dose would be most beneficial in these vulnerable groups. however, it has been recently recommended for all age groups from all backgrounds (11). 5. limitations this study has several limitations. first, the number of included studies was limited and they did not encompass all types of vaccines, and the publications existed only on mrna-based and inactivated vaccines. we also could not conduct a meta-analysis due to the limited number of studies and their heterogeneity. regarding the study populations, 7 out of 12 studies were performed on healthcare workers, an important group vulnerable to the covid-19. this can be considered both a strength and a limitation, as healthcare workers are a special and vulnerable group and require specific attention, but this means that the number of population-based studies on the general population were limited. on the other hand, only one study targeted another important group, the immunocompromised patients, and further specific studies on this group are required. furthermore, although the studies had acceptable quality assessment scores, many of them lacked adequate matching for confounders. a strength of the present review was that included studies were conducted in 15 countries, making the results more reliable worldwide. overall, we could deduce the benefits of booster doses using the existing evidence. 6. conclusion studies have shown that the immunity due to covid-19 vaccines diminishes over time. such decrease is more evident in older people and those with specific underlying diseases, such as immunodeficiencies. furthermore, new covid-19 variants, particularly omicron, are on the rise and it has been documented that they may evade the immunity rendered by vaccines; therefore, immediate efforts are required to refurbish the vaccines to trigger the appropriate antibody responses against these new variants. moreover, booster doses are recommended to enhance the overall immunity of the general population against covid-19. 7. declarations 7.1. acknowledgments the present study was conducted in collaboration with khalkhal university of medical sciences, iranian research center for hiv/aids, tehran university of medical sciences, and walailak university. 7.2. availability of data and materials all data generated or analyzed during this study are included in this published article. 7.3. authors’ contributions (1) the conception and design of the study:esmaeil mehraeen, seyedahmad seyedalinaghi this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e53 (2) acquisition of data: amirali karimi, alireza shojaei (3) analysis and interpretation of data: ava amiri, sara mahdiabadi (4) drafting the article: amirata fakhfouri, armin razi, hengameh mojdeganlou, paniz mojdeganlou, alireza barzegary, zahra pashaei, amir masoud afsahi, parnian shobeiri, omid dadras (5) revising it critically for important intellectual content: seyedahmad seyedalinaghi, omid dadras, esmaeil mehraeen (6) final approval of the version to be submitted: all authors 7.4. funding and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.5. competing interests the authors declare that there is no conflict of interest regarding the publication of this manuscript. 7.6. ethics approval and consent to participate not applicable. 7.7. consent to publication not applicable. references 1. who coronavirus (covid-19) dashboard [available from: https://covid19.who.int/. 2. mehraeen e, oliaei s, seyedalinaghi s, karimi a, mirzapour p, afsahi am, et al. covid-19 in pediatrics: a systematic review of current knowledge and practice. infect disord drug targets. 2022; 22(5): e290921196908. 3. mehraeen e, seyedalinaghi s, karimi a. can children of the sputnik v vaccine recipients become symptomatic? human vaccines & immunotherapeutics. 2021;17(10):3500-1. 4. mehraeen e, dadras o, afsahi am, karimi a, pour mm, mirzapour p, et al. vaccines for covid-19: a systematic review of feasibility and effectiveness. infect disord drug targets. 2022;22(2):e230921196758. 5. sheikhbahaei e, mirghaderi sp, moharrami a, habibi d, motififard m, mortazavi smj. incidence of symptomatic covid-19 in unvaccinated patients within one month after elective total joint arthroplasty: a multicenter study. arthroplast today. 2022;14:110-5. 6. tartof sy, slezak jm, fischer h, hong v, ackerson bk, ranasinghe on, et al. effectiveness of mrna bnt162b2 covid-19 vaccine up to 6 months in a large integrated health system in the usa: a retrospective cohort study. lancet (london, england). 2021;398(10309):1407-16. 7. glück v, grobecker s, köstler j, tydykov l, bertok m, weidlich t, et al. immunity after covid-19 and vaccination: follow-up study over 1 year among medical personnel. infection. 2022;50(2):439-46. 8. achiron a, mandel m, dreyer-alster s, harari g, gurevich m. humoral sars-cov-2 igg decay within 6 months in covid-19 healthy vaccinees: the need for a booster vaccine dose? eur j intern med. 2021;94:105-7. 9. thomas sj, moreira ed, jr., kitchin n, absalon j, gurtman a, lockhart s, et al. safety and efficacy of the bnt162b2 mrna covid-19 vaccine through 6 months. n engl j med. 2021;385(19):1761-73. 10. fda. vaccines and related biological products advisory committee briefing document us food and drug administration 2021 [available from: https://www.fda.gov/media/152161/download. 11. fast he, zell e, murthy bp, murthy n, meng l, scharf lg, et al. booster and additional primary dose covid19 vaccinations among adults aged ≥65 years united states, august 13, 2021-november 19, 2021. mmwr morbidity and mortality weekly report. 2021;70(50):1735-9. 12. juno ja, wheatley ak. boosting immunity to covid-19 vaccines. nature medicine. 2021;27(11):1874-5. 13. wang z, muecksch f, schaefer-babajew d, finkin s, viant c, gaebler c, et al. naturally enhanced neutralizing breadth against sars-cov-2 one year after infection. nature. 2021;595(7867):426-31. 14. kiefer mk, allen kd, russo jr, ma’ayeh m, gee se, kniss d, et al. decline in sars-cov-2 antibodies over 6-month follow-up in obstetrical healthcare workers. am j reprod immunol. 2021;86(6):e13490. 15. harris rj, whitaker hj, andrews nj, aiano f, aminchowdhury z, flood j, et al. serological surveillance of sars-cov-2: six-month trends and antibody response in a cohort of public health workers. j infect. 2021;82(5):162-9. 16. naaber p, tserel l, kangro k, sepp e, jürjenson v, adamson a, et al. dynamics of antibody response to bnt162b2 vaccine after six months: a longitudinal prospective study. lancet reg health eur. 2021;10:100208. 17. tré-hardy m, cupaiolo r, wilmet a, antoine-moussiaux t, della vecchia a, horeanga a, et al. immunogenicity of mrna-1273 covid vaccine after 6 months surveillance in health care workers; a third dose is necessary. j infect. 2021;83(5):559-64. 18. terpos e, trougakos ip, karalis v, ntanasis-stathopoulos i, gumeni s, apostolakou f, et al. kinetics of anti-sarscov-2 antibody responses 3 months post complete vaccination with bnt162b2; a prospective study in 283 health workers. cells. 2021;10(8):1942. 19. erice a, varillas-delgado d, caballero c. decline of antibody titres 3 months after two doses of bnt162b2 in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 6 non-immunocompromised adults. clin microbiol infect. 2022;28(1):139.e1-.e4. 20. favresse j, bayart jl, mullier f, elsen m, eucher c, van eeckhoudt s, et al. antibody titres decline 3-month postvaccination with bnt162b2. emerging microbes & infections. 2021;10(1):1495-8. 21. guo w, duan k, zhang y, yuan z, zhang yb, wang z, et al. safety and immunogenicity of an inactivated sarscov-2 vaccine in healthy adults aged 18 years or older: a randomized, double-blind, placebo-controlled, phase 1/2 trial. eclinicalmedicine. 2021;38:101010. 22. waldhorn i, holland r, goshen-lago t, shirman y, szwarcwort-cohen m, reiner-benaim a, et al. six month efficacy and toxicity profile of bnt162b2 vaccine in cancer patients with solid tumors. cancer discovery. 2021. 23. mohapatra rk, tiwari r, sarangi ak, islam mr, chakraborty c, dhama k. omicron (b.1.1.529) variant of sars-cov-2: concerns, challenges, and recent updates. j med virol. 2022;94(6):2336-42. 24. hedges jf, thompson ma, snyder dt, robison a, taylor mp, jutila ma. titers, prevalence, and duration of sarscov-2 antibodies in a local covid-19 outbreak and following vaccination. vaccines (basel). 2021;9(6):587. 25. zakarya k, kutumbetov l, orynbayev m, abduraimov y, sultankulova k, kassenov m, et al. safety and immunogenicity of a qazcovid-in® inactivated whole-virion vaccine against covid-19 in healthy adults: a singlecentre, randomised, single-blind, placebo-controlled phase 1 and an open-label phase 2 clinical trials with a 6 months follow-up in kazakhstan. eclinicalmedicine. 2021;39:101078. 26. pouquet m, decarreaux d, prévot-monsacré p, hervé c, werner a, grosgogeat b, et al. nationwide seroprevalence of sars-cov-2 igg antibodies among four groups of primary health-care workers and their household contacts 6 months after the initiation of the covid-19 vaccination campaign in france: seroprim study protocol. pathogens. 2021;10(7):911. 27. vicenti i, basso m, gatti f, scaggiante r, boccuto a, zago d, et al. faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second bnt162b2 mrna covid-19 vaccine dose. int j infect dis. 2021;112:40-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e53 figure 1: prisma 2020 flow diagram for this systematic review. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 8 table 1: summary of findings based on each study first author (reference) type of study study population (n) male (%) mean age (sd) type time after vaccination changes in antibody levels vaccine efficacy against author’s opinion about booster dose summary of findings infection disease severity mortality a.erice (19) spain, 2021 observational study adults 62% 46.0 years (sd 11.4 years) mrna vaccine serum samples were obtained a mean of 40.1 days (sd 2.8 days) and 88.8 days (sd 2.8 days) after the second dose of bnt162b2 median [iqr] anti-rbd titres 1.5 months after vaccination were 9,356 [5,844 16,876] au/ml; three months after vaccination, median anti-rbd titres had declined to 3,952 [2,190 8,561] au/ml (p <0.001) advanced severe covid-19 has been reported in fully vaccinated individuals a median of 39.5 days after the second dose of bnt162b2 a low anti-rbd antibody titer is one aspect related tothe advanced sars-cov-2 infection after complete vaccination with bnt162b2 j.favresse (20) belgium, 2021 ongoing multicenter, prospective, and interventional study healthcare professionals 22.5 43 mrna covid19 vaccine 3 months the maximal antibody response was reached between days 28 and 42 (2204 versus 1,863; p=0.20), with a 48.8–57.7-fold increase compared to day 14 (i.e. 38.2 u/ml) as calculated by the one-compartmental model, the estimated half-life of antibodies observed from data collected until 90 days after vaccination for seronegative members was 55 days (95% ci: 37–107 days) w.gou (21) china, 2021 clinical trial healthy adults aged ≥18 41.1 and 59.5 in twoage groups the mean (standard deviation) age was 43.1 (9.6) years in participants aged 18–59 years and 66.7 (4.3) in those aged ≥60 years (79.2% aged 60–69 years) inactivated 90 days geometric mean titerof neutralizing antibody on day 90 after the third injection ranged from 87 to 129, respectively, among participants receiving three doses of vaccines the initial results of the phase 1/2 trial among adults, including those aged 60 years or older, showed that the inactivated vaccine against sars-cov-2 was safe and immunogenic. j.f. hedges (24) usa, 2021 cohort 41.8 mrna 6 months the neutralization titers had declined 6 months after vaccination,similar to 6 months after natural infection. the antibody responses induced by vaccination were significantly higher than those induced by natural infection. therefore, the study suggests that vaccination is still vital, even for those naturally infected or diagnosed with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e53 table 1: summary of findings based on each study first author (reference) type of study study population (n) male (%) mean age (sd) type time after vaccination changes in antibody levels vaccine efficacy against author’s opinion about booster dose summary of findings infection disease severity mortality p.naaber (16) estonia, 2021 longitudinal observational healthcare workers 42 42.5 mrna 6 months in the first serum sample, the median anti-s-rbd igg reached 540.0 au/ml (iqr 64.5-1102.0). in the following tests, a progressive decay of antibodies was seen, up to the value of 55.7 au/ml (iqr 26.2-84.7) at the 6-month follow-up this study may allow to define a protective antibody threshold, below which the risk of break-through infections significantly increases and which could, hence, guide the time point when to offer a booster dose. the study approves the persistence of anti-s-rbd neutralizing antibodies through 6 months after the vaccination. m.pouquet (26) france, 2021 longitudinal survey health care workers rnabased vaccines 6 months e. terpos (18) prospective study health care workers 32.9 48 mrna 3 months three months after the second vaccination (i.e., on d111), the decline in nab titers was even more prominent with a median inhibition of 92.7% (sd 11.8) the longitudinal study is continuing in order to determine the time point of nabs decrease below the positivity threshold, and the fading of protective immunity against covid-19; when a booster vaccine dose might be necessary. both nabs and anti-s-rbd antibodies, the maximum levels are seen at day 36. a statistically significant decrease in both types of antibodies was observed after day36 up to day111 s. j. thomas (9) 6 countries, usa, turkey, germany, south africa, brazil, argentina; 2021 clinical trial adolescents and adults 50.9 51 mrna 6 months vaccine efficacy of 91.1% bnt162b2 effectively prevents covid-19 for up to 6 months after the second dose across various populations, despite the emergence of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 10 table 1: summary of findings based on each study first author (reference) type of study study population (n) male (%) mean age (sd) type time after vaccination changes in antibody levels vaccine efficacy against author’s opinion about booster dose summary of findings infection disease severity mortality sars-cov-2 variants, including the beta variant, and the vaccine continues to show a promising safety profile. m. tréhardy(17) belgium, 2021 prospective study health care workers 25.4 50.1 mrna 5 months antibody values went from 400 [400-400] au/ml at 3 months after first injection to 221.0 [202.3-241.2] au/ml at 6 months after first injection, and from 400 [400-400] au/ml at to 400 [365.0-400] au/ml at introducing a booster dose, under certain circumstances, could have a significant impact in terms of public health all applicants still had detectable sars-cov-2 igg antibodies up to 5 months after complete vaccination. i.vicenti(27) italy, 2021 longitudinal study health care workers (hcws) 39.1 mrna 3 months previously infected vaccinated hcws (n=23): 546 uninfected vaccinated hcws (n=13): 20 in uninfected hcws completing the two-dose vaccine program, a third mrna vaccine dose is a sensible option to counteract the substantial ntab decline occurring at a significantly higher rate compared with previously infected, vaccinated hcws median ntab at v2_90 (90±2 days after the second dose) was still significantly higher than median ntab at v_0 (before receiving the first dose) both in hcws with past mild disease (p=0.01) and in those experiencing asymptomatic infection (p=0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e53 table 1: summary of findings based on each study first author (reference) type of study study population (n) male (%) mean age (sd) type time after vaccination changes in antibody levels vaccine efficacy against author’s opinion about booster dose summary of findings infection disease severity mortality i.waldhorn(22) israel, 2021 prospective follow-up report of the primary study cancer patients with solid tumors 55 66 mrna 166 ± 29 days both cohorts depicted a drastic decline in serology titer over time,but the titer remained above the threshold value there was no notable difference in the median absolute serology titer between the seropositive individuals within the two cohorts (patients vs. controls). k. zakaria(25) kazakhstan, 2021 clinical trial adults aged 18 years and older 77.3 28 inactivated wholevirion 6 months an increase in the titers of neutralizing antibody was statistically significant, reaching geometric mean titer of 5.1 (95% ci 3·5–7·6) on day 21 and geometric mean titer of 100 (95% ci 77–129) on day 42. on day180 after the first immunization, the geometric mean titer dropped to 7 (95% ci 5–7) in both trials, specific antibodies were detected in mna and elisa on study day 180, but the titers dropped in comparison today 42. sd: standard deviation; iqr: interquartile range; ci: confidence interval; s-rbd: spike protein receptor-binding domain; ig: immunoglobulin; nab/ntab: neutralizing antibody; mna:microneutralization assay; elisa:enzyme-linked immunosorbent assay. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem o. dadras et al. 12 table 2: the results of newcastle-ottawa scale (nos) risk of bias assessment the first author (reference) selection (out of 4) comparability (out of 2) exposure/ outcome (out of 3) total score (out of 9) a.erice(19) *** ** 5 j.favresse(20) *** * ** 6 w.gou(21) *** *** 6 j.f. hedges(24) **** * ** 7 p.naaber(16) **** * ** 7 m.pouquet(26) *** * *** 7 e. terpos(18) **** * * 6 s. j. thomas(9) **** * ** 7 m. tré-hardy(17) *** * *** 7 i.vicenti(27) **** * *** 8 i.waldhorn(22) **** * *** 8 k. zakaria(25) **** * ** 7 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e37 rev i ew art i c l e early versus late decompression for traumatic spinal cord injuries; a systematic review and meta-analysis mahmoud yousefifard1,2, vafa rahimi-movaghar1, masoud baikpour3, parisa ghelichkhani4, mostafa hosseini5,1,6 ∗, ali moghadas jafari7, heidar aziznejad8, abbas tafakhori9,10 1. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. 2. physiology research center and department of physiology, faculty of medicine, iran university of medical sciences, tehran, iran. 3. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 4. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 5. pediatric chronic kidney diseases research center, children’s hospital medical center, tehran university of medical sciences, tehran, iran 6. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 7. department of emergency medicine, school of medicine, bushehr university of medical sciences, bushehr, iran. 8. the persian gulf tropical medicine research center, bushehr university of medical sciences, bushehr, iran. 9. department of neurology, school of medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 10.iranian center of neurological research, tehran university of medical sciences, tehran, iran. received: may 2016; accepted: jun 2016; published online: 11 january 2017 abstract: introduction: despite the vast number of surveys, no consensus has been reached on the optimum timing of spinal decompression surgery. this systematic review and meta-analysis aimed to compare the effects of early and late spinal decompression surgery on neurologic improvement and post-surgical complications in patients with traumatic spinal cord injuries. methods: two independent reviewers carried out an extended search in electronic databases. data of neurological outcome and post-surgery complication were extracted. finally, pooled relative risk (rr) with a 95% confidence interval (ci) was reported for comparing of efficacy of early and late surgical decompression. results: eventually 22 studies were included. the pooled rr was 0.77 (95% ci: 0.68-0.89) for at least one grade neurological improvement, and 0.84 (95% ci: 0.77-0.92) for at least two grade improvement. pooled rr for surgical decompression performed within 12 hours after the injury was 0.26 (95% ci: 0.13-0.52; p<0.001), while it was 0.75 (95% ci: 0.63-0.90; p=0.002) when the procedure was performed within 24 hours, and 0.93 (95% ci: 0.76-1.14; p=0.48) when it was carried out in the first 72 hours after the injury. surgical decompression performed within 24 hours after injury was found to be associated with significantly lower rates of post-surgical complications (rr=0.77; 95% ci: 0.68-0.86; p<0.001). conclusion: the findings of this study indicate that early spinal decompression surgery can improve neurologic recovery and is associated with less post-surgical complications. the optimum efficacy is observed when the procedure is performed within 12 hours of the injury. keywords: decompression, surgical; early surgical decompression; late surgery; injured spinal cord. © copyright (2017) shahid beheshti university of medical sciences cite this article as: yousefifard m, rahimi-movaghar v, baikpour m, ghelichkhani p, hosseini m, moghadas jafari a, aziznejad h, tafakhori a. early versus late decompression for traumatic spinal cord injuries; a systematic review and meta-analysis. emergency. 2017; 5(1): e37. ∗corresponding author: mostafa hosseini; department of epidemiology and biostatistics, school of public health, poursina ave, tehran, iran; tel/fax: +982188989125 ; email: mhossein110@yahoo.com 1. introduction spinal decompression surgery is beneficial for decreasing the probability of post spinal cord injury (sci) neurological impairments. findings of experimental and clinical studies have confirmed that it improves patient outcomes by prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefifard et al. 2 venting the activation of secondary injury mechanisms (1, 2). however, there is an ongoing controversy regarding the best time for surgical intervention. some clinical trials are indicative of better motor and neurologic recovery with early surgical decompression compared to late interventions(2, 3), while others have shown otherwise (4), one way to reach a consensus is conducting a systematic review and metaanalysis. in this regard, two meta-analyses have been published in 2004 and 2006 (5, 6). in addition, another study has been carried out in 2013 to assess different surgical schedules in scis, but presence of publication bias and considerable heterogeneity has kept the authors from arriving at a reliable conclusion on this matter (7). in recent years, a significant number of clinical trials and cohort studies have compared the efficacies of early and late surgical decompression, which provide a suitable basis for conducting a meta-analysis on human studies. in this regard, the present study aimed to compare the effects of late and early surgical decompression on motor and neurologic recovery of sci patients through a systematic review and meta-analysis. 2. methods to find the maximum number of related articles, an extended search was carried out in databases of medline (via pubmed), embase (via ovidsp), central, scopus, web of science (biosis), and proquest from january 2000 to the end of october 2015. search strategy was based on combining terms related to “surgical decompression” with keywords related to “spinal cord injuries” (panel 1). the keywords were selected using mesh and emtree through manual search in the titles and abstracts of related articles and eventually by consulting experts. in searching pubmed interface, the archived articles in pubmed central database were also included. other than the mentioned systematic search, manual search was performed in google scholar and google search engine. the authors of related articles were also contacted via email and were asked to provide us with any unpublished data, unrecorded information or unpublished dissertations they had. in cases where data were not available online, the authors were contacted. if no response was received, a reminder was sent a week later. if the author did not respond again, other authors of the article were asked for the data through social networks such as researchgate and linkedin. bibliographies of relevant studies were also hand-searched to find further articles or unpublished data. 2.1. inclusion criteria: all the clinical trials (class i), controlled prospective cohorts (class ii), case series and retrospective studies (class iii) that evaluated and compared the effects of early spinal decompression surgery with late surgery on outcome of spinal cord injuries were included. since a meta-analysis published in 2004 had evaluated the articles published before the year 2000 (6), in this study only studies carried out after that were included. sample population comprised of patients with spinal cord injuries without any gender or ethnic restrictions. studies were included, in which the neurologic outcome was assessed based on american spinal injury association (aisa) score, american spinal injury association impairment scale (ais), and the frankel score. studying patients younger than 14 years old and non-traumatic patients, not categorizing subjects into two groups of early and late interventions, using a temporal cut-off of more than 72 hours for classification of patients, and following the subjects for less than 6 months (for assessing neurological outcome) were regarded as exclusion criteria. in addition, studies that assessed post-surgical complication were included. 2.2. quality assessment and data extraction: the search results were combined and duplicate studies were removed using the endnote software (version x5, thomson reuters, 2011). the methodology of the studies was assessed and controlled by two independent researchers and the summaries of extracted sources were recorded in data extraction forms. in cases of disagreement, a third reviewer evaluated the findings and the inconsistency was resolved through discussion. data collection was done blinded to the authors, journals, institutions and departments of the articles. the findings of the systematic search were recorded in a checklist designed based on the prisma statement guidelines (8). study design, characteristics of sample populations (age, gender, mechanism of sci), type of injury (complete, incomplete), etiology (motor-vehicle accidents, falling, etc.), location of injury (cervical, thoracic, lumbar), sample size, temporal cut-off point used for classification of the patients, final outcome (neurologic outcome, post-surgical complications), and possible biases were extracted. in cases of duplicate results, the study with the greater sample size was included. when the results were presented at different times, the findings of the last follow up were included. in cases that results were presented as charts, the data extraction method suggested by sistrom and mergo was utilized (9). 2.3. quality assessment the quality of the included studies was assessed based on the guideline proposed by the agency for healthcare research and quality’s methods guide for effectiveness and comparthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e37 table 1: characteristics of included studies author, year study design timing (hours) severity sample size (early/late) age* sex male (%) location of injury outcome score follow up (month) bourassamoreau et al. 2013 5 rcs 24 i / c 90 / 110 47.9±17.6 77.7 c1-l2 complication na post-surgery bourassamoreau et al. 2015 6 rcs 24 c 38 / 15 43.7±18.5 91 c1-l2 neurologic asia 6 cengiz et al. 2008 7 rct 8 i / c 12 / 15 41.4±14.7 66.7 t8-l2 neurologic/complication asia 12 chen et al. 2012 8 quasi-rct 8 i / c 99 / 110 42.1 ± 13.8 82.8 cervical neurologic/complication asia/ais 12 dobran et al. 2015 1 2 rcs 12 i / c 27 / 30 50.2 ± 21.3 77.2 cervical neurologic ais 24 dvorak et al. 2015 1 3 pcs 24 i / c 355 / 533 45.7 76.5 c1-l2 neurologic/complication asia 6 ehsaei et al. 2013 1 5 quasi-rct 24 i 15 / 15 35.9±17.2 90 t11l2 neurologic/complication frankel 6 fehlings et al. 2012 1 8 pcs 24 i / c 131 / 91 47.46±16.9 75.4 cervical neurologic/complication ais 6 guest et al. 2002 2 1 rcs 24 i / c 16 / 34 45 (1477) 62 cervical neurologic asia >13 gupta et al. 2015 2 2 pcs 48 i / c 23 / 46 35.7±11.5 88 cervical neurologic/complication asia 12 jug et al. 2015 2 5 pcs 8 i / c 22 / 20 48(25.872.8) 81 cervical neurologic asia 6 kerwin et al. 2005 2 7 rcs 72 i / c 174 / 125 39.6 72.6 c1-l2 complication na post-surgery liu et al. 2015 3 0 rcs 72 i / c 172 / 317 41.4±12.0 76.6 c3-c7 neurologic/complication frankel 6 *, data were present as mean ± standard deviation or mean and (range). rcs: retrospective cohort study; pcs: prospective cohort study; rct: randomized control trial; i: incomplete injury; c: complete injury; neu: neurologic; comp: complication; asia: american spinal; injury association; ais: american spinal injury association impairment scale impairment scale; nr: not reported; na: not applicable. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefifard et al. 4 table 1: characteristics of included studies (continuous) author, year study design timing (hours) severitysample size (early/late) age* sex male (%) location of injury outcome score follow up (month) lukas et al. 2012 3 1 rcs 24 i / c 15 / 12 nr nr c3-l1 neurologic frankel 6 mckinley et al. 2004 3 2 pcs 24 i / c 33 / 140 37.65±15.83 78.8 c3-l2 neurologic/complication asia 12 medress et al. 2015 3 3 rcs 72 i / c 2249 /1099 50.34 68.9 cervical complication na post-surgery pollard et al. 2003 3 7 rcs 24 c 86 / 242 35±15.5 nr thoracic neurologic asia 12 rahimi et al. 2005 3 9 rcs 24 i / c 12 / 32 26.7 ± 8.6 90 c3-l2 neurologic frankel 6 rahimi et al. 2014 3 8 rct 24 i / c 15 / 18 35±12.1 71 t5-l1 neurologic/complication ais 12 sapkas et al. 2007 4 1 rcs 72 i / c 31 / 36 36 (1672) 73.1 c3-c7 neurologic frankel 12 stevens et al. 2010 4 4 rcs 24 i / c 16 / 34 47.7±16.2 82 cervical thoracic neurologic/complication frankel 16 umerani et al. 2014 4 5 pcs 24 i / c 34 / 64 39.2 (1965) 78.6 c3-t1 neurologic ais 6 *, data were present as mean ± standard deviation or mean and (range). rcs: retrospective cohort study; pcs: prospective cohort study; rct: randomized control trial; i: incomplete injury; c: complete injury; neu: neurologic; comp: complication; asia: american spinal; injury association; ais: american spinal injury association impairment scale impairment scale; nr: not reported; na: not applicable. ative effectiveness reviews (10). the reviewers rated the articles and classified them into three levels of good, fair, and poor based on their design, biases, sample selection, randomization, performance, and outcome report and eventually, only studies rated as fair and good were included. 2.4. statistical analyses data on neurologic outcome were reported in two forms in the studies. some surveys had compared the mean and standard deviations of asia score or frankel score between the two groups of early and late surgical decompression, while others had compered the improvement rate of one/two grade(s) in ais/frankel score between the two mentioned groups. for the studies with the first form, standardized mean differences (smd) were calculated with a confidence interval of 95% (95% ci) based on hedge’s g. for studies that had compared one/two grade(s) improvement in ais/frankel scores, data were recorded as frequency of improved or not improved patients in each group and a pooled relative risk (rr) with a confidence interval of 95% was reported. pooled prevalence of post-surgical complications was assessed for each group and pooled rr was calculated for comparison of early and late surgery in decreasing postsurgical complications. in order to identify publication bias, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e37 panel 1: keywords used for search in embase and medline databases database search terms medline (pubmed) (“decompression, surgical”[mesh] or “surgical decompression*”[tiab] or "early versus late surgical decompression”[tiab] or "early surgical decompression"[tiab] or "late surgical decompression"[tiab] or "delay* decompression"[tiab] or “immediate decompression’[tiab] or “delay* treatment"[tiab] or "early treatment"[tiab] or “late surgery”[tiab] or "delay* surgery”[tiab]) and (spinal cord injuries [mh] or spinal cord injury [tiab] or spinal cord injuries [tiab] or spinal cord contusion [tiab] or spinal cord transection [tiab] or injured spinal cord [tiab] or traumatic central cord syndrome [tiab]) embase (ovidsp) exp "decompression, surgical"/ or ("surgical decompression" or "early versus late surgical decompression" or "early surgical decompression" or "late surgical decompression" or "delay decompression" or "immediate decompression" or "delay treatment" or "early treatment" or "late surgery" or "delay surgery").ti,ab. and exp spinal cord injuries/ or ("spinal cord injury" or "spinal cord injuries" or "spinal cord contusion" or "spinal cord transection" or "injured spinal cord" or "traumatic central cord syndrome").ti,ab. table 2: subgroup analysis of at least one improvement in neurological status for comparing early and late surgical decompression characteristic no of subject (early/late) p for publication bias * model p for heterogeneity (i2 ) relative risk (95% ci) p overall 553 /745 0.66 fem 0.02 (48.8%) 0.77 (0.68-0.88) 0.02 data gathering method prospective 242 /269 0.55 fem 0.22 (26.8%) 0.70 (0.68-0.89) <0.001 retrospective 311 /476 >0.99 rem 0.02 (59.9%) 0.85 (0.71-1.03) 0.09 type of study cohort 511 /697 0.92 fem 0.03 (49.1%) 0.81 (0.70-0.93) 0.003 control trial 42 /48 0.73 fem 0.19 (40.1%) 0.54 (0.39-0.81) 0.003 time cut off# 8-12 hours 39 /45 >0.99 fem 0.55 (0.0%) 0.26 (0.13-0.52) <0.001 0-24 hours 216 /399 0.76 fem 0.90 (0.0%) 0.75 (0.63-0.90) 0.002 0-72 hours 298 /301 0.73 rem 0.05 (66.6%) 0.93 (0.76-1.14) 0.48 location of injury cervical 403 /604 0.73 rem 0.02 (62.1%) 0.82 (0.71-0.94) 0.008 thoracolumbar 42 /48 0.31 fem 0.19 (40.1%) 0.54 (0.36-0.81) 0.003 follow up period 6 months 403 /604 0.73 rem 0.11 (40.4%) 0.87 (0.75-1.02) 0.08 ≥ 12 months 42 /48 0.31 fem 0.12 (42.2%) 0.53 (0.39-0.71) <0.001 * based of egger’s (begg’s) test #, time cut point for definition of early surgery group rem: random effect model; fem: fixed effect; ci: confidence interval. the egger’s and begg’s tests were used (11). heterogeneity was assessed through i2 tests and a p-value of less than 0.1 along with an i2 greater than 50 percent were considered as positive heterogeneity. fixed effect model was used for homogenous, and random effect model was applied for heterogeneous analyses. subgroup analysis was performed to recognize the source of heterogeneity. it is worth mentioning that meta-analysis was only carried out when the data were reported by at least three studies. statistical analyses were done via stata version 12.0 software (stata corporation, college station, tx). a p value less than 0.05 was regarded as statistically significant in all the analyses. 3. results: 3.1. search and screening results in the extended search, 103 potentially eligible studies were screened, 29 of which met the inclusion criteria. among them, eleven studies had not presented data required for meta-analysis (12-22). corresponding authors of these studies were contacted and three of them responded (14, 17, 21), two of which provided data (17, 21). no answers were received from the authors of the other 8 surveys after sending two reminders. therefore, 18 studies were included from the systematic search. manual search yielded 4 more articles. eventually 22 studies were included in the meta-analysis (figure 1) (4, 17, 21, 23-41). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefifard et al. 6 table 3: subgroup analysis of at least one improvement in neurological status for comparing early and late surgical decompression characteristic prevalence (95% ci) publication bias* (p value) model p for heterogeneity (i2 ) relative risk (95% ci) p early group late group overall 0.29 (0.28-0.31) 0.38 (0.36-0.40) 0.66 fem 0.001 (65.2%) 0.84 (0.72-0.99) 0.035 data gathering method prospective 0.36 (0.32-0.39) 0.52 (0.48-0.56) fem 0.22 (26.8%) 0.77 (0.68-0.87) <0.001 retrospective 0.28 (0.27-0.30) 0.34 (0.32-0.36) 0.81 rem 0.003 (75.0%) 0.95 (0.76-1.19) 0.16 type of study cohort 0.37 (0.30-0.45) 0.55 (0.48-0.63) 0.71 rem 0.001 (71.3%) 0.87 (0.73-1.03) 0.10 control trial 0.29 (0.28-0.31) 0.37 (0.35-0.39) >0.99 rem 0.05 (60.8%) 0.50 (0.21-1.19) 0.12 time cut off# 0-24 hours 0.37 (0.34-0.41) 0.51 (0.47-0.55) 0.37 fem 0.17 (32.4%) 0.77 (0.68-0.86) <0.001 0-72 hours 0.28 (0.26-0.29) 0.33 (0.31-0.36) >0.99 rem 0.003 (78.6%) 0.99 (0.77-1.27) 0.93 location of injury cervical 0.29 (0.27-0.30) 0.36 (0.34-0.38) >0.99 rem 0.001 (79.5%) 0.89 (0.72-1.11) 0.30 thoracolumbar 0.11 (0.0-0.22) 0.41 (0.28-0.54) >0.99 fem 0.64 (0.0%) 0.33 (0.15-0.73) 0.006 * based of egger’s (begg’s) test. #, time cut point for definition of early surgery group. rem: random effect model; fem: fixed effect; ci: confidence interval. 3.2. characteristics of included studies included studies comprised of two randomized clinical trials (9.09%), two quasi-experimental studies (9.09%), six prospective cohorts (27.27%) and 12 retrospective cohorts (44.55%). these studies had evaluated 6803 patients (3665 subjects in the early spinal decompression surgery group and 3138 patients in the late spinal decompression surgery group). early surgical decompression was defined as performing the operation within 8 hours in three studies (13.64%), 12 hours in one survey (4.55%), 24 hours in 13 studies (59.09%), 48 hours in one (4.55%), and 72 hours in four (18.18%). two studies had assessed patients with complete scis, one had evaluated patients with incomplete scis (4.55%) and the rest included both types of injury (86.36%). neurologic outcome was assessed in 9 studies (40.91%), post-surgical complications were evaluated in 3 (13.64%), and both of them were compared in 10 surveys (45.45%). patients were followed for at least 6 months in 9 studies (40.91%), 12 months in 7 surveys (31.82%) and more than 16 months in two studies (9.09%). 19 articles were written in english , 2 in farsi (17, 21) and one in czech (34). table 1 presents the characteristics of included studies. 4. meta-analysis 4.1. neurologic outcome six studies had compared the neurologic score of patients between the two groups of early and late spinal decompression surgery via mean and standard deviation (26, 30, 35, 37-39), 5 of which used the asia score (26, 30, 35, 37, 38) and one used the frankel score (39). in this section, no publication bias was observed (p=0.99), but a moderate heterogeneity was observed (i-squared = 50.5%; p = 0.072). the pooled smd of early and late spinal decompression surgery in neurological recovery was 0.18 (95% ci: 0.03-0.33). in other words, early surgical decompression led to moderately better neurologic outcome in patients compared to late treatment. neurological improvement rate was used for comparison between the two groups in 14 studies (4, 17, 21, 24, 25, 27, 29, 31, 32, 34, 38-41). the pooled rr was 0.77 (95% ci: 0.68-0.89) for at least one grade neurological improvement and 0.84 (95% ci: 0.770.92) for at least two grade improvement (figure 2). no publication bias was found (p=0.66) but a moderate heterogeneity was identified (i-squared=48.8%; p = 0.02). subgroup analysis was performed to find the source of heterogeneity for at least one grade improvement in neurological status (table 2). pooled rr yielded from clinical trials was significantly lower than that of the cohort studies (0.54 vs. 0.81). in other words, in clinical trials the efficacy reported for early spinal decompression surgery was higher than the reports of cohort studies. pooled rr for early spinal decompression surgery in improvement of neurological outcome was found to be 0.26 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e37 (95% ci: 0.13-0.52; p < 0.001) when the procedure was performed within 12 hours after injury, 0.75 (95% ci: 0.63-0.90; p = 0.002) when performed within 24 hours, and 0.93 (95% ci: 0.76-1.14; p = 0.48) when carried out within 72 hours. therefore, neurologic improvement declined with the rise in the interval between injury and surgery, so that there is no significant difference between the efficacy of the treatment when performed within 72 hours or after that. follow-up period was another effective factor. pooled rr for studies with 6 month follow-ups was 0.87 (95% ci: 0.75-1.02; p = 0.08), while it was 0.53 (95% ci: 0.39-0.71; p < 0.001) for studies with at least 12 month follow-ups. 4.2. post-surgical complications post-surgical complications were evaluated in 12 studies (4, 17, 23, 25, 26, 29, 31, 33, 35, 36, 38, 40). the prevalence of complications in the early spinal decompression surgery group was 0.29 (95% ci: 0.28-0.31) and in the late group was 0.38 (95% ci: 0.36-0.40). no publication bias was present (p=0.66) but a significant heterogeneity was observed (isquared = 65.2%; p = 0.001). meta-analysis found the pooled rr of early spinal decompression surgery for post-surgical complications to be 0.84 (95% ci: 0.72-0.99), which indicates that the prevalence of these complications is lower in patients who had undergone early surgical decompression (p = 0.035). subgroup analysis showed that the prevalence of complications reported in prospective studies was significantly lower in the early treatment group compared to the late intervention group (prevalence = 0.36 vs. 0.52; rr=0.77; p < 0.001). however, the figures reported in retrospective studies did not differ significantly between the two groups (0.28 vs. 0.34; rr=0.95; p = 0.16). moreover, the prevalence of post-surgical complications was found to be significantly lower when the procedure was performed within 24 hours compared to later interventions (prevalence = 0.37 vs. 0.51; rr=0.77; p < 0.001). this figure was not significantly different whether the patient was treated within 72 hours of injury or after that (prevalence = 0.28 vs. 0.33; rr=0.99; p = 0.93). 5. discussion: in recent years, spinal decompression surgery in the early hours of sci has drawn major attention. some believe that early surgical decompression in these patients can lead to better neurologic recovery and decrease post-surgical complications. however, disagreements still exist on this matter. the present meta-analysis aimed to draw a comprehensive conclusion on this subject through conducting an extended search in electronic databases. the findings of this study showed that early spinal decompression surgery, within 24 hours of injury, is associated with improved neurologic recovery and decreased post-surgical complications compared to late intervention. definitions of early surgical decompression in different studies vary regarding the temporal cut-off point, which ranges from 8 to 72 hours. accordingly, subgroup analysis was performed to assess the neurologic recovery of the patients, which indicated that longer interval between injury and spinal decompression surgery, is associated with lower treatment efficacy. performing surgery in the first 12 hours after trauma was associated with the best neurologic recovery, while the outcomes of treatment within 72 hours and after that did not differ significantly. in this regard, it can be concluded that the optimum time for surgical decompression is the first 12 hours after injury. considering the fact that it is not possible for most patients to undergo surgery in the first 12 hours, the cut-off point could be considered the first 24 hours. the higher efficacy of spinal decompression surgery in the first 12 hours can be attributed to the pathologic mechanism of spinal traumatic injuries. neural injury occurs during the first hours after sci leading to hypo-perfusion, ischemia, and eventually death of neural cells (first phase of injury), while the majority of injuries occur in the second phase, which starts within few days after trauma. this phase includes apoptosis induction, formation of glial scar, central chromatolysis, disruption in expression of myelin genes, myelin destruction in remained axons, glutamate hyper-stimulation, immune cells attacking the site of lesion and release of inflammatory cytokines, endothelial injury induced by reperfusion-ischemia, and etc. (42). hence, decompression in the first hours after injury can prevent secondary injuries or lower its severity. in line with the results of this study, van middendrop et al. found that surgical intervention in the first 24 hours after injury is associated with better neurologic recovery, compared to the same treatment after 24 hours (7). however, the efficacy they reported was considerably higher than this study. these researchers found that surgery in the first 24 hours increases neurologic recovery by 2.5 times, while in the present meta-analysis this efficacy was found to be 1.3 times (rr=0.77). this difference could partly be attributed to the evident publication bias in the study of van middendrop. in their meta-analysis, only two studies with a cut-off point of 24 hours were included for classification of subjects to two groups of early and late, while the present meta-analysis included 13 of such surveys. in another systematic review in 2015, anderson et al. evaluated 9 studies aiming to assess the optimal timing of surgical decompression for acute traumatic central cord syndrome and they stated that surgery in the first 24 hours is a safe and efficient method. these authors declared that there is still not enough evidence on this matter, based on which a solid guideline could be proposed for early surgery (43). the present meta-analysis showed that the follow-up duration can influence the yielded results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefifard et al. 8 figure 1: flowchart of the study. no significant difference was found between the neurologic recovery of early and late surgical decompression in studies with 6 month follow-ups (rr=0.87; 95% ci: 0.75-1.02), while evaluating the studies with at least 12 months of follow up showed significant difference between the two groups (rr=0.53; 95% ci: 0.39-0.71). this might be due to the incomplete neurologic recovery within 6 months. although the majority of recoveries occur in the first 3 to 6 months after injury, to assess the efficacy of a treatment the maximum improvement should be considered for comparison in order to reach more reliable conclusions. accordingly, it is suggested that the patients be followed for at least one year in the future studies. as presented in this meta-analysis, lower prevalence of post-surgical complications is another advantage of performing the surgery in the first 24 hours. in their overall analysis, van middendrop et al. found the difference between the rates of post-surgical complications in early and late surgical groups to be considerable but statistically insignificant (or=0.71; 95% ci: 0.49-1.04).(7) the overall analysis in the present study also found the mentioned difference to be near the borderline (rr=0.84; 95% ci: 0.72-0.99), but when subgroup analysis was performed for temporal cut-off point, it was illustrated that classification of patients based on a cut-off point of 72 hours can change the differences between the two groups. the differences were found to be significant when cut-off point was set to 24 hours. subgroup analysis could not be performed based on severity of injury since most included studies had evaluated both complete and incomplete injuries and had not separated the two. another limitation of this study was existence of heterogeneity between the included surveys, which led to the meta-analysis being designed based on random effect model for these cases. although we did our best to include studies with similar methodologies and controlling for confounding factors, even in ideal situations this cannot be completely obtained. for instance, in most this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 9 emergency. 2017; 5 (1): e37 figure 2: forest plot of neuralgic improvement relative risk (rr) in individual studies and pooled estimate using the random effects model for comparing early and late surgical decompression. patients scis are accompanied by other injuries, a factor that can affect the final outcome of the treatments and prevalence of post-surgical complications but is overlooked by most studies. in the present survey, only two clinical trials and two quasi-experimental studies were included and the majority of the articles were retrospective studies. therefore, the results could be subject to selection bias. on the other hand, the retrospective nature of these studies could have influenced the collected data, which is indicative of possible bias in this section. nevertheless, an extended search was conducted in electronic databases and a great effort was made to acquire data through contacting the authors, extracting information from charts and figures, and calculation of means and standard deviations. although the last two methods are not very precise, the figures they extract are quite similar to the actual numbers, so these methods are frequently applied in meta-analyses (44, 45). most importantly, in addition to overall evaluation of the relation between timing of surgery and neurologic improvement, subgroup analysis was performed based on different factors, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefifard et al. 10 figure 3: forest plot of post-surgery complication relative risk (rr) in individual studies and pooled estimate using the random effects model for comparing early and late surgical decompression. which considerably helped reduce biases. 6. conclusion: the findings of this meta-analysis showed that early spinal decompression surgery is associated with better neurologic improvement and lower prevalence of post-surgical complications, compared to late intervention. the efficacy is most prominent when the surgery is performed within the first 12 hours after injury. accordingly, it is recommended that surgical decompression be carried out in the first 12 hours after injury and postponing the procedure to later than 24 hours is associated with significant decrease in neurologic improvement and more post-surgical complications. 7. appendix 7.1. acknowledgements this research has been supported by a tehran university of medical sciences and health services grant and sina trauma and surgery research center, tehran university of medical sciences grant (number: 94-02-184-26097). 7.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors 7.3. conflict of interest there are no conflicts of interests to report. 7.4. funding none declared. references 1. sjovold sg, mattucci sf, choo am, liu j, dvorak mf, kwon bk, et al. histological effects of residual compression sustained for 60 minutes at different depths in a novel rat spinal cord injury contusion model. j neurotrauma. 2013;30(15):1374-84. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 11 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a systematic review and metaanalysis. emergency. 2015;3(4):127-36. 45. hosseini m, yousefifard m, aziznejad h, nasirinezhad f. the effect of bone marrow derived mesenchymal stem cell transplantation on allodynia and hyperalgesia in neuropathic animals: a systematic review with metaanalysis. biol blood marrow transplant. 2015;29(1):153744. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: meta-analysis discussion: conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e64 or i g i n a l re s e a rc h predictive factors of outcome in cases of out-of-hospital cardiac arrest due to traffic accident injuries in thailand; a national database study thongpitak huabbangyang1, chunlanee sangketchon1∗, sakditat ittiphisit2, kanittha uoun3, chomkamol saumok3 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. faculty of medicine, vajira hospital, navamindradhiraj university, bangkok, thailand. 3. division of emergency medical service and disaster, faculty of medicine, vajira hospital, navamindradhiraj university, bangkok, thailand. received: june 2022; accepted: july 2022; published online: 16 august 2022 abstract: introduction: traffic accident injury is one of the global leading causes of death and an important public health problem. this study aimed to evaluate the predictive factors of return of spontaneous circulation (rosc) at the scene in out-of-hospital cardiac arrest (ohca) due to traffic accidents. methods: this retrospective crosssectional study was conducted on cases of ohca due to traffic accident, who were resuscitated at the scene by emergency medical services (ems) in bankok, thiland, from january 1, 2020, to december 31, 2020 (1 year). patients were divided into two groups of with and without rosc and independent predictive factors of outcome were evaluated. results: 2400 ohca cases met the inclusion criteria, among them, 1728 (72.0%) achieved rosc at the scene. facial injury (adjusted or = 2.17, 95%ci: 1.37–3.44, p = 0.001); prehospital airway management using bag valve mask (adjusted or = 1.69, 95%ci: 1.21–2.34, p = 0.002), and endotracheal tube (adjusted or = 3.88, 95%ci: 1.84–8.18, p <0.001); and prehospital fluid therapy using normal saline (adjusted or = 4.24, 95%ci: 3.12–5.77, p <0.001), ringer lactate (adjusted or = 5.13, 95%ci: 3.47–7.61, p <0.001), and other solutions (adjusted or = 5.25, 95%ci: 2.16–12.8, p <0.001) were independent predictive factors of rosc at the scene in ohca due to traffic accidents. conclusion: based on the findings, the rate of rosc at the scene for cases with ohca due to traffic accidents, serviced by ems was high, i.e., 72%, and three independent predictive factors of rosc at the scene were facial injury, prehospital airway management, and prehospital fluid management. keywords: prognosis; emergency medical services; heart arrest; patient outcome assessment; mortality; accidents, traffic cite this article as: huabbangyang t, sangketchon c, ittiphisit s, uoun k, saumok c. predictive factors of outcome in cases of out-ofhospital cardiac arrest due to traffic accident injuries in thailand; a national database study. arch acad emerg med. 2022; 10(1): e64. https://doi.org/10.22037/aaem.v10i1.1700. 1. introduction the world health organization reported the annual average number of deaths due to traffic accidents as 1.35 million. the majority of deaths occurred in vulnerable populations, including pedestrians and motorcyclists. about 93% of deaths occurred in low-to-middle income countries, traffic accident ∗corresponding author: chunlanee sangketchon; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. postal code: 10300 tel: +66 22443000, e-mail: chunlanee@nmu.ac.th, orcid: https://orcid.org/00000003-4509-1527. injury was the leading cause of death in those aged 5–29 years (1). thai road safety collaboration reported the cumulative number of injuries to be 417,935 in 2021 from january to may, and the number of deaths from traffic accidents was 6,513. every hour, two died due to traffic accidents in thailand (2). two-thirds of road accident victims in thailand were male (80%) and aged <40 years. about 80% of the injured and deceased were motorcyclists. traffic accidents were an important public health problem leading to injuries, disabilities, and mortalities in thailand, a developing country, causing vast effects on individuals, families, societies, and the nation as a whole (3). thailand had the highest rate of road accident mortality in south east asia, i.e., this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 2 32.7 per 100,000 population (4). emergency medical services (ems) were used as a tool to address this issue and focused on prehospital management of injured patients, appending two important concepts, the golden period or golden hour and the platinum 10 minutes. regarding the golden period, the first 60 minutes for injured patients, starting from accident, is a period with significantly increased morbidity and mortality. the platinum 10 minutes within the golden hour means that paramedics have at most 10 minutes at the scene to manage severely injured patients for survival rate improvement (5). bystander cardiopulmonary resuscitation (cpr) increased the survival rate of injured patients with cardiac arrest from an accident, as indicated in previous studies (6, 7). for initial cardiac rhythm, shockable rhythm resulted in survival improvement (8-10). pediatric patients had a higher survival rate by receiving cpr for out-of-hospital cardiopulmonary arrest (ohca) due to accidents, as compared to adult patients with a survival rate of approximately 17.8% (95% ci; 15.1–20.8%). geographical areas where accidents happened between the city and countryside were associated with inpatient survival and hospital discharge (9, 10). thailand is 513,120 square kilometers (198,120 square miles), divided into 77 provinces. its mean population was 66.19 million in december 2020. in the 2021 statistical report, 854,118 traffic accidents and 13,235 traffic accident mortalities occurred, which showed that the country had the highest number of injured and deceased patients due to traffic accidents worldwide (11). every traffic accident led to loss, including deaths, disabilities, and inevitable traffic congestion, an obstacle for ambulances and ems teams to access the scene. a traffic accident was one of the three most common events managed by the thai emergency medical units. out-of-hospital ems was initiated when emergency medical act b.e.2551 was declared. the national institute for emergency medicine was the backbone supporting emergency medical missions in thailand. in thailand, the emergency hotline is 1669. the provincial dispatch center manages each province, except for bangkok where the erawan center and bangkok ems center are located. the present study aimed to evaluate prognostic factors associated with the return of spontaneous circulation (rosc) at the scene and determine the rate of rosc at the scene for those injured with ohca due to traffic accidents, serviced by ems. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on cases of ohca due to traffic accident, who were resuscitated at the scene by ems in bankok, thiland, from january 1, 2020, to december 31, 2020 (1 year). patients were divided into two groups of with and without rosc and independent predictive factors of outcome were evaluated. the ethical approval of the study protocol was granted by the committee on human rights related to research involving human subjects, faculty of medicine, vajira hospital, navamindradhiraj university (coa. 168/2564). the requirement for informed consent was waived due to the retrospective design. the study data were kept confidential to ensure the privacy of the studied participants. this study was conducted in accordance with the declaration of helsinki. 2.2. participants traffic accident patients aged >18 years, coded as 25 red 1 symptom group based on emergency medical triage protocol and criteria-based dispatch (cbd) of thailand, defined as a traffic accident with cardiac arrest, who received advanced cardiovascular life support from the advanced life support (als) team were eligible for study. traffic accident patients serviced by ems in bangkok who died at the scene (death on arrival), those who were evaluated as deceased when ems arrived, those who were deemed unsuitable for cpr by the als team leader, patients whose relatives denied treatment and transportation, those receiving cpr during transfer, patients with discordant cbd coding to the actual incident, and those with incomplete data were excluded. rosc at the scene was defined as the presence of palpable pulse after cpr at the scene of trauma. 2.3. data gathering data were collected from the national institute for emergency medicine database, thailand, which gathered data on traffic accidents with symptom group 25 based on the thailand emergency medical triage protocol and criteria-based dispatch (cbd), from the database of information technology for emergency medical system (items). only symptom group 25 red 1, i.e., traffic accident patients with cardiac arrest, was selected for this study. the items database of the national institute for emergency medicine is the national database recording thai ems operation data including patient management at the scene and during transportation. the ems team recorded data in the patient record form and then transferred them into the items database within that day or month. only authorized people could record and go over the data, including paramedics, emergency nurse practitioners (enps), or advanced emergency medical technicians (aemts). the study included the injured and emergency operation unit’s data, such as sex, age, operation time, type of wounds, type of orthopedic injuries, type of hemorrhage, type of body part injured, the response time (minute), duration of transfer to the hospital (minute), duration from hospital to the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e64 base station (minute), distance from the base station to scene (kilometer), distance from the scene to the hospital (kilometer), distance from hospital to the base station (kilometer), prehospital airway management, prehospital hemorrhage control, prehospital airway management, prehospital fluid management, prehospital immobilization, and prehospital automated external defibrillator (aed) /defibrillation, medication during cpr, and rosc on the scene. the concept of emergency medicine in thailand appends the anglo-american and franco-german models. in thailand, the out-of-hospital emergency staff includes emergency physicians (eps), paramedics, enps, aemts, emergency medical technicians (emts), and emergency medical responders, which operate under an emergency medical director, which can be divided into off-line and online medical directions. in general, the staff operates under a predetermined off-line medical direction, as a protocol created by the emergency medical director, which is different in each operation unit or hospital, depending on administrative potential and existent resources. there are two tiers of ambulances in thailand, i.e., advanced life support (als) and basic life support. regarding emergency medical operations for traffic accident patients with cardiac arrest, most ems teams in the study area consisted of at least three staff members during each operation, including eps, paramedics, or enps as operation leaders and aemts and emts as members. 2.4. outcome measures the primary objective was to evaluate predictive factors of rosc at the scene in cases with ohca due to traffic accidents, who were serviced by ems. the secondary objective was to determine the rosc rate of the injured with ohca due to traffic accidents at the scene. 2.5. statistical analysis sample size was calculated using two independent proportions (12). the statistical significance level of 0.05 and test power of 80% were considered. statistical values for sample size were calculated based on jun gs et al. (9) study that reported survival rates of male and female patients with both ohca and rosc on the scene to be 0.3332% (1988/5966; p1= 0.3332) and 27.08% (615/2271; p2= 0.2708), respectively. the sample size ratio of females to males was 0.38 (2271:5966). therefore, calculated female and male sample sizes were at least 1,524 and 580, consecutively. hence, a sample size of 2,104 was determined. however, due to the retrospective design of the study, collecting data from medical records, the sample size was increased to compensate for incomplete data of 10% (13). the final sample size was 2,400. a descriptive analysis was performed to examine variable distribution. continuous variables are presented as mean ± standard deviation (sd) or median and interquartile range (iqr), and categorical variables are presented as frequencies and proportions. when comparing the two groups, differences were evaluated using independent t-test or mannwhitney u test for numeric variables and chi-square test or fisher’s exact test for categorical variables. the survival rate of the injured patients with ohca at the scene who were serviced by ems was reported as frequency distribution and percentage (incidence) with a 95% confidence interval (ci). predictive factors associated with rosc at the scene for the injured with ohca due to traffic accidents serviced by ems were reported as frequency distribution and percentage, categorized based on survival, assessed with crude analysis using either the chi-squared test or fisher’s exact test based on the type of variable. multivariable analysis using multiple logistic regression analysis was reported as odds ratio (or) and 95% ci. ibm spss statistics for windows, version 26.0. armonk, ny, usa: ibm corp. was used. all statistical tests were considered statistically significant at a p-value of ≤0.05. 3. results 3.1. baseline characteristics of studied cases 2400 cases of ohca with rosc at the scene with the mean age of 40.07 ± 18.47 years, who were resuscitated by ems during the study period were studied. the rosc rate at the scene was 72.0% (1728 patients). there was no difference between survived and deceased cases regarding sex distribution (78.9% vs. 78% male; p = 0.629) and mean age (40.07 ± 18.47 vs. 40.05 ± 18.85 years, p = 0.985). table 1 compares the baseline characteristics between patients with and without rosc. 3.2. associated factors of rosc at the scene based on univariate analysis, associated factors of rosc at the scene for cases of ohca due to traffic accidents were facial injury (or = 2.08, 95%ci: 1.32–3.26, p = 0.001); prehospital airway management using bag valve mask (bvm) (or = 2.4–4, 95%ci: 1.80–3.30, p <0.001), endotracheal tube (ett) (or = 5.79, 95%ci: 2.80–11.94, p <0.001), or supra-glottic airway devices (or = 2.17, 95%ci: 1.23–3.81, p = 0.007); prehospital fluid management with normal saline (nss) (or = 4.72, 95%ci: 3.51–6.34, p <0.001), lactated ringer’s solution (rls) (or = 5.71, 95%ci: 3.89–8.37, p <0.001), and other solutions (or = 5.71, 95%ci: 2.36–13.79, p <0.001); prehospital immobilization including splint (or = 2.78, 95%ci: 1.59–4.88, p <0.001) and collar with long spinal board (or = 2.59, 95%ci: 1.92–3.51, p <0.001); and medication during the cpr process (or = 1.47, 95%ci: 1.14–1.90, p = 0.003) (table 2). multivariable analysis using multiple logistic regression analysis and backward stepwise selection method, showed that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 4 table 1: comparing the baseline characteristics between patients with and without return of spontaneous circulation (rosc) variables rosc on scene (n = 2400) p value yes (n=1728) no (n = 672) sex male 1363 (78.9) 524 (78.0) 0.629 female 365 (21.1) 148 (22.0) age (year) 0–19 260 (15.0) 101 (15.0) 20–39 624 (36.1) 243 (36.2) 0.999 40–59 536 (31.0) 207 (30.8) >60 308 (17.8) 121 (18.0) shift morning (8.00–15.59) 501 (29.0) 188 (28.0) evening (16.00–23.59) 910 (52.7) 353 (52.5) 0.772 night (0.00–7.59) 317 (18.3) 131 (19.5) type of wounds none 73 (4.2) 29 (4.3) cut/laceration 1213 (70.2) 473 (70.4) abrasion 271 (15.7) 93 (13.8) 0.690 other 70 (4.1) 32 (4.8) unknown 101 (5.8) 45 (6.7) type of orthopedic injuries none 501 (29.0) 174 (25.9) closed fracture 542 (31.4) 217 (32.3) open fracture 446 (25.8) 184 (27.4) 0.668 dislocation 40 (2.3) 16 (2.4) unknown 199 (11.5) 81 (12.1) hemorrhage status none 200 (11.6) 75 (11.2) stopped external bleeding 608 (35.2) 182 (27.1) active external bleeding 489 (28.3) 233 (34.7) 0.002 internal hemorrhage 230 (13.3) 101 (15.0) unknown 201 (11.6) 81 (12.1) location of trauma head/neck 1199 (69.4) 490 (72.9) face 122 (7.1) 24 (3.6) extremity 56 (3.2) 19 (2.8) 0.035 other 144 (8.3) 56 (8.3) multiple injuries 38 (2.2) 11 (1.6) unknown 169 (9.8) 72 (10.7) response time (minute) median (iqr) 10 (7–14) 10 (7–15) 0.430 ≤8 697 (40.3) 257 (38.2) 0.347 >8 1031 (59.7) 415 (61.8) scene to hospital time (minute) median (iqr) 7 (4–10) 7 (5–12) 0.475 ≤8 1041 (60.2) 388 (57.7) 0.262 >8 687 (39.8) 284 (42.3) time from hospital to ems station (minute) median (iqr) 0 (0.01–0.01) 0.01 (0.01–0.01) 0.004 ≤1 1589 (92.0) 583 (86.8) <0.001 >1 139 (8.0) 89 (13.2) distance from ems station to scene (km) median (iqr) 7 (4–11) 7 (4–11) 0.249 ≤10 1254 (72.6) 481 (71.6) >10 448 (25.9) 182 (27.1) 0.817 unknown 26 (1.5) 9 (1.3) distance from scene to hospital (km) median (iqr) 7 (4–11) 7 (4–11) 0.194 ≤10 1257 (72.7) 449 (66.8) >10 445 (25.8) 179 (26.6) <0.001 unknown 26 (1.5) 44 (6.5) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e64 table 1: comparing the baseline characteristics between patients with and without return of spontaneous circulation (rosc) variables rosc on scene (n = 2400) p value yes (n=1728) no (n = 672) distance from hospital to ems station (km) median (iqr) 5 (2–11) 7 (3–15) 0.176 <10 103 (6.0) 54 (8.0) ≥10 36 (2.1) 30 (4.5) <0.001 unknown 1589 (92) 588 (87.5) prehospital airway management no 100 (5.8) 89 (13.2) bvm 1507 (87.2) 550 (81.8) <0.001 ett 65 (3.8) 10 (1.5) supra-glottic airway devices 56 (3.2) 23 (3.4) prehospital hemorrhage control no 342 (19.8) 148 (22) pressure dressing 1127 (65.2) 430 (64) 0.444 dressing 259 (15.0) 94 (14) prehospital fluid management no 82 (4.7) 131 (19.5) nss 1371 (79.3) 464 (69.0) <0.001 rls 250 (14.5) 70 (10.4) other 25 (1.4) 7 (1.1) prehospital immobilization no 97 (5.6) 90 (13.4) splint 66 (3.8) 22 (3.3) <0.001 collar with long spinal board 1565 (90.6) 560 (83.3) prehospital aed/defibrillation no 1640 (94.9) 630 (93.8) 0.261 yes 88 (5.1) 42 (6.3) medication during cpr no 266 (15.4) 118 (17.6) yes 897 (51.9) 270 (40.2) <0.001 unknown 565 (32.7) 284 (42.3) data are presented as number (%) or mean ± standard deviation or median (interquartile range). p-value corresponds to independent samples t-test, mann-whitney u test, chi-square test, or fisher’s exact test. rosc, return of spontaneous circulation; ems, emergency medical services; iqr, interquartile range; bvm, bag valve mask; ett, endotracheal tube; nss, normal saline; rls, ringer lactate; aed, automated external defibrillator; cpr, cardiopulmonary resuscitation. facial injury (adjusted or = 2.17, 95%ci: 1.37–3.44, p = 0.001); prehospital airway management using bvm (adjusted or = 1.69, 95%ci: 1.21–2.34, p = 0.002) and ett (adjusted or = 3.88, 95%ci: 1.84–8.18, p <0.001); and prehospital fluid therapy using normal saline (adjusted or = 4.24, 95%ci: 3.12–5.77, p <0.001), ringer lactate (adjusted or = 5.13, 95%ci: 3.47–7.61, p <0.001), and other solutions (adjusted or = 5.25, 95%ci: 2.16–12.8, p <0.001) were the independent predictive factors of rosc at the scene in ohca due to traffic accidents (table 2). 4. discussion in the present study, the rate of rosc at the scene for cases of ohca due to traffic accidents, serviced by ems was high, i.e., 72%, and three predictive factors of rosc at the scene were facial injury, prehospital airway management, and prehospital fluid management. the high rate of rosc at the scene among traffic accident patients probably means that the traffic accident patients with cardiac arrest usually had a high survival rate, consistent with the results of a study in thailand, reporting that the survival rate of those injured due to traffic accidents, managed by ems, and admitted to tertiary hospitals was 97.9% at the scene (14). moreover, the result was comparable to the authors’ previous study, which showed that the rosc rate among traffic accident patients was higher than non-traumatic patients at the scene (15). the results of the present study were consistent with those of a previous study reporting short and quite good survival and recovery time for traffic accident patients (16). most traffic accident patients with ohca survived with a mortality rate of only 7.4% in the emergency department in addis ababa, ethiopia (17). a facial injury could predict rosc at the scene for traffic accident patients with ohca, managed by ems in the present study, a finding consistent with that of a previous study this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 6 table 2: multivariate analysis of factors associated with on-the-scene return of spontaneous circulation in patients with out-of-hospital cardiopulmonary arrest due to traffic accident factors multivariate analysis or adjusted 95%ci p value location of trauma head/neck 1.00 reference face 2.17 (1.37–3.44) 0.001 extremity 1.17 (0.68–2.01) 0.570 other 1.01 (0.72–1.42) 0.948 multiple injuries 1.55 (0.77–3.12) 0.220 unknown 1.03 (0.76–1.41) 0.833 prehospital airway management no 1.00 reference bag valve mask 1.69 (1.21–2.34) 0.002 endotracheal tube 3.88 (1.84–8.18) <0.001 supraglottic airway devices 1.41 (0.78–2.54) 0.253 prehospital fluid management no 1.00 reference normal saline 4.24 (3.12–5.77) <0.001 ringer lactate 5.13 (3.47–7.61) <0.001 other 5.25 (2.16–12.8) <0.001 hosmer and lemeshow test: chi-square = 7.060, df = 4, p-value = 0.133, constant = -0.922. or: odds ratio; ci: confidence interval. demonstrating that the injured body part affected the chance of survival, especially in those with a single injury, such as the face and extremity. they also reported that injury to critical body parts, such as the chest, abdomen, pelvis, head, and neck, and multiple injuries negatively affected survival (18). prehospital airway management, such as bvm and ett in traffic accident patients with ohca, can also be used to predict rosc at the scene, a finding consistent with the authors’ previous national database study, comparing rosc rates between patient groups receiving bvm and ett. no statistically significant difference in prehospital rosc rate was detected (19), which conflicted with that of a previous study indicating that traffic accident patients intubated with ett by ems had a better outcome than those without ett intubation and prehospital ett intubation in indicated patients. patients with ohca might have a lower mortality rate and also improved early neurological outcomes (20), a finding comparable to the study indicating that those with ett intubation in out-of-hospital patients had better outcome than the group without ett intubation, including decreased mortality rate, and prehospital ett intubation was not associated with increased morbidities and mortalities (21). however, ett intubation in our study area depended on the protocols of each area, and only eps and paramedics were permitted to intubate, which limited its performance. for als teams with neither eps nor paramedics, bvm was used instead of ett. prehospital fluid management was a factor that could predict rosc at the scene for traffic accident patients with ohca, managed by ems. rls, nss, and other fluid replacements were well known for prehospital fluid resuscitation in traumatic arrest, as an isotonic crystalloid solution is suggested to be the first choice in the injured with shock due to blood loss and ohca (22). a previous clinical trial study indicated that rls was superior to nss in clinical outcomes, admission duration, and survival (23, 24). however, a decision in fluid replacement selection for traffic accident patients with ohca in the present study relied on the team leader, and the protocol determined in each area was different. 5. limitations the most important limitation of the present study was for items database, as some of the important factors reported by previous studies to affect survival of the injured patients by were not recorded for ohca patients, such as bystander cpr and initial cardiac rhythm. the second limitation was the inevitable bias associated with a retrospective study, as some data were lost, leading to exclusion. third, since data were collected from the database in the items, treatment results were limited, accessible only to treatment at the scene; thus, no in-hospital treatment and patient outcomes, treatment in the emergency department, surgery, or other treatments were included, resulting in evaluating only the outcomes at the scene by emergency unit or ems team. fourth, the severity and mechanism of injury were not considered in the study. lastly, ems operation units in the study area were markedly different in operation staff, resources, and protocols for each area, which probably leads to the inability to generalize the present study’s results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e64 6. conclusion based on the findings, the rosc rate of ohca cases due to traffic accidents, serviced by ems was high at the scene, i.e., 72%, and three independent predictive factors of rosc at the scene were facial injury, prehospital airway management, and prehospital fluid management. 7. declarations 7.1. acknowledgments the authors were grateful to navamindradhiraj university research fund, national institute for emergency medicine for supporting data in the study, chunlanee sangketchon md, chief of department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university for always assisting and facilitating researching, anucha kamsom, division of biostatistic, faculty of medicine vajira hospital, navamindradhiraj university for statistical consultancy and dr. aniwat berpan for acting as an english consultant for this study. 7.2. authors’ contributions design of the study by thongpitak huabbangyang; data acquisition by thongpitak huabbangyang, chunlanee sangketchon, sakditat ittiphisit and kanittha uoun; data analysis and interpretation by thongpitak huabbangyang, chunlanee sangketchon and chomkamol saumok; drafting the manuscript by thongpitak huabbangyang; revision of the manuscript by thongpitak huabbangyang, chunlanee sangketchon, sakditat ittiphisit, kanittha uoun and chomkamol saumok; the final version of the manuscript is approved by all the authors. 7.3. funding and supports the study was funded by navamindradhiraj university (no. 102/2564) who played no role in study design, data collection, data analysis, or writing the manuscript. 7.4. conflict of interest the authors report no conflict of interest. references 1. who. world report on road traffic injury 2021 [2021 june 28]. available from: https://www.who.int/newsroom/fact-sheets/detail/road-traffic-injuries. 2. limited ravpc. statistics and information throughout the year [2021 june 28]. available from: https://www.thairsc.com. 3. chadbunchachai w, suphanchaimaj w, settasatien a, jinwong t. road traffic injuries in thailand: current situation. j med assoc thai. 2012;95(suppl 7):s274-81. 4. aramrerng p, sutham k, wittayachamnankul b, kaewpaengchan w, laosuksri w, sairai r, et al. [survival of out-of-hospital cardiac arrest of traumatic patients who received medical care from emergency medical service system]. j health syst res. 2020;14:43-50. thai. 5. saeheng p, chavanasporn k, phanrangsee p, waikila n, santaweephol n, noosila n, et al. the response time and the adequacy of emergency medical service team for elderly patients in bangkok: a case study of bangkok emergency medical service center,(erawan center). vajira med j. 2019;63(supplement):s65-72. 6. djarv t, axelsson c, herlitz j, stromsoe a, israelsson j, claesson a. traumatic cardiac arrest in sweden 19902016-a population-based national cohort study. scand j trauma resusc emerg med. 2018;26(1):1-8. 7. zwingmann j, lefering r, feucht m, südkamp np, strohm pc, hammer t. outcome and predictors for successful resuscitation in the emergency room of adult patients in traumatic cardiorespiratory arrest. crit care. 2016;20(1):1-10. 8. inamasu j, miyatake s, yagi t, noma s. resuscitation outcomes of cardiac arrest patients who caused witnessed non-fatal road traffic accidents while driving. resuscitation. 2017;119:e15-e6. 9. jun gs, kim jg, choi hy, kang gh, kim w, jang ys, et al. prognostic factors related with outcomes in traumatic out-of-hospital cardiac arrest patients without prehospital return of spontaneous circulation: a nationwide observational study. clin exp emerg med. 2020;7(1):14-20. 10. beck b, bray je, cameron p, straney l, andrew e, bernard s, et al. predicting outcomes in traumatic out-of-hospital cardiac arrest: the relevance of utstein factors. emerg med j. 2017;34(12):786-92. 11. department sae. thailand statistical report 2020 [2021 june 28]. available from: http://www.bangkok.go.th/upload/user/00000130/bma _statistics%202563/ebook%2063.pdf. 12. rosner b. fundamentals of biostatistics. fifth edition ed: duxbury thomson learning–united state usa; 2000. 13. p pitisuttithum, picheansunthorn c. textbook of clinical research fourth edition. revised and expanded ed. bangkok: faculty of tropical medicine, mahidol university: faculty of tropical medicine, mahidol university; 2011. 14. wongvatanakij p, tadadej c, meyai a, suriyawongpaisal p. relation of factor on survival outcomes among traumatic patients at the tertiary care hospital admitted for traffic accidents in phuket province. srinagarind med j. 2019;34(1):52-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 8 15. huabbangyang t, soion t, promdee a, nguanjinda k, chamchan a, chaisorn r, et al. factors associated with successful resuscitation during out-of-hospital cardiac arrest performed by surgico medical ambulance and rescue team (smart), division of emergency medical service and disaster, faculty of medicine vajira hospital, navamindrad. j med assoc thai. 2021;104(9):1488-96. 16. tesfay k, assefa m, zenebe d, gebremicael m, kebede g, gebrekirstos h. road traffic injured patients with severe gcs and organ injury had a poor prognosis: a retrospective cohort study. bmc public health. 2019;19(1):749. 17. seid m, azazh a, enquselassie f, yisma e. injury characteristics and outcome of road traffic accident among victims at adult emergency department of tikur anbessa specialized hospital, addis ababa, ethiopia: a prospective hospital based study. bmc emerg med. 2015;15(1):10. 18. pooncharoen t, hoacharoensirichai p, chaisorn r, pongpan p, nithimathachoke a, rojsaengroeng r. factors affecting the survival rate of prehospital traffic accident patients in thailand. thai j emerg med. 2019;1(1):27-39. 19. yuksen c, phattharapornjaroen p, kreethep w, suwanmano c, jenpanitpong c, nonnongku r, et al. bagvalve mask versus endotracheal intubation in out-ofhospital cardiac arrest on return of spontaneous circulation: a national database study. open access emerg med. 2020;12:43-6. 20. hoffmann m, czorlich p, lehmann w, spiro as, rueger jm, lefering r. the impact of prehospital intubation with and without sedation on outcome in trauma patients with a gcs of 8 or less. j neurosurg anesthesiol. 2017;29(2):161-7. 21. denninghoff kr, nuño t, pauls q, yeatts sd, silbergleit r, palesch yy, et al. prehospital intubation is associated with favorable outcomes and lower mortality in protect iii. prehosp emerg care. 2017;21(5):539-44. 22. ramesh g, uma j, farhath s. fluid resuscitation in trauma: what are the best strategies and fluids? int j emerg med. 2019;12(1):38. 23. mane as. fluid resuscitation: ringer lactate versus normal saline–a clinical study. int j contemp med res. 2017;4:2290-3. 24. martini wz, cortez ds, dubick ma. comparisons of normal saline and lactated ringer’s resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe hemorrhagic shock. scand j trauma, resusc emerg med. 2013;21(1):86. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e81 rev i ew art i c l e diagnostic performance of magnetic resonance imaging for detection of acute appendicitis in pregnant women; a systematic review and meta-analysis mohsen motavaselian1, fatemeh bayati2, reza amani-beni3, amirreza khalaji4, sara haghverdi5, zeynab abdollahi6, arash sarrafzadeh7, amir-masood rafie manzelat8, amir rigi9, razman arabzadeh bahri10, zahra nakhaee11, mahta fadaei12, hajar ghasemi falaverjani13, sara malekpour-dehkordi14, maryam hoseinpour14, matin bidares15, sarvenaz zandkarimi16, rasha ahmadi17, dorsa beheshtiparvar8, seyed-amirabbas ahadiat18, mohsen farshi8, mehrdad farrokhi19∗ 1. school of medicine, shahid sadoughi university of medical sciences, yazd, iran. 2. usern office, kermanshah university of medical sciences, kermanshah, iran. 3. school of medicine, isfahan university of medical sciences, isfahan, iran. 4. liver and gastrointestinal diseases research center, tabriz university of medical sciences, tabriz, iran. 5. kermanshah university of medical sciences, kermanshah, iran. 6. ahvaz jundishapur university of medical sciences, ahvaz, iran. 7. school of dentistry, arak university of medical sciences, arak, iran. 8. school of medicine, isfahan university of medical sciences, isfahan, iran. 9. islamic azad university, zahedan branch, zahedan, iran. 10.tehran university of medical sciences, tehran, iran. 11.gonabad university, gonabad, iran. 12.school of medicine, shahid beheshti university of medical sciences, tehran, iran. 13.department of internal medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 14.ahvaz jundishapur university of medical sciences, ahvaz, iran. 15.islamic azad university of najafabad, najafabad, iran. 16.faculty of pharmacy, islamic azad university of tehran medical sciences, tehran, iran. 17.shariati hospital, tehran university of medical science, tehran, iran. 18.research center of biochemistry and nutrition in metabolic disorder, kashan university of medical science. kashan, iran. 19.men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: july 2022; accepted: august 2022; published online: 6 october 2022 abstract: introduction: the diagnosis of acute appendicitis (aa) in pregnant women is commonly challenging owing to the normal results of laboratory tests, organ displacement, and normal physiological inflammatory alterations. this meta-analysis aimed to investigate the accuracy of magnetic resonance imaging (mri) in diagnosis of aa in pregnant women. methods: two investigators independently performed a comprehensive systematic literature search of electronic databases including medline, cochrane central, embase, web of science, scopus, and google scholar to identify studies that reported accuracy of mri for diagnosis of aa in pregnant women from inception to april 1, 2022. results: our systematic search identified a total of 525 published papers. finally, a total of 26 papers were included in the meta-analysis. the pooled sensitivity and specificity of mri in diagnosis of aa in pregnant women were 0.92 (95% ci: 0.88–0.95) and 0.98 (95% ci 0.97–0.98), respectively. the pooled positive likelihood ratio and negative likelihood ratio were 29.52 (95% ci: 21.90–39.81) and 0.10 (95% ci: 0.04-0.25), respectively. the area under hierarchical summary receiver operating characteristic (hsroc) curve indicated that the accuracy of mri for diagnosis of aa in pregnant women is 99%. conclusion: this meta-analysis showed that mri has high sensitivity, specificity, and accuracy for diagnosis of aa in pregnant women and can be used as a first-line imaging modality for suspected cases of aa during pregnancy. furthermore, it should be noted that when the result of ultrasonography is inconclusive, the use of mri can reduce unnecessary appendectomy in pregnant patients. keywords: appendicitis; magnetic resonance imaging; meta-analysis; pregnancy this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. motavaselian et al. 2 cite this article as: motavaselian m, bayati f, amani-beni r, khalaji a, haghverdi s, abdollahi z, et al. diagnostic performance of magnetic resonance imaging for detection of acute appendicitis in pregnant women; a systematic review and meta-analysis. arch acad emerg med. 2022; 10(1): e81. https://doi.org/10.22037/aaem.v10i1.1727. 1. introduction acute appendicitis (aa) is known as one of the most prevalent non-obstetric causes of acute abdominal pain requiring surgical intervention during pregnancy (1, 2). however, in pregnant cases, the diagnosis of aa is commonly challenging owing to the normal results of laboratory tests, organ displacement due to the altered anatomy of gravid uterus, and normal physiological inflammatory alterations including increased white blood cell count and left shift of neutrophils. moreover, there is a broad range of manifestations and differential diagnoses due to other causes of acute abdominal pain in pregnant women (3-5). these challenges can delay the diagnosis of aa and surgery, which increases the rate of appendiceal perforation, morbidity, and mortality of pregnant women and the fetus. on the other hand, false-positive diagnosis can result in unnecessary surgeries, increasing risk of unfavorable outcomes including fetus loss and premature labor. therefore, prompt and accurate diagnosis of aa during pregnancy is needed to reduce morbidity and mortality among both fetuses and pregnant women (4, 6). despite recent advances in imaging modalities, there are still a considerable minority of patients in whom the appendix is not confidently detected. furthermore, while ultrasonography is the first-line recommended diagnostic imaging, the majority of investigations are inconclusive or the appendix is not identified. in this regard, previous investigations have shown that computed tomography (ct) scan may have a better accuracy compared to ultrasonography (7-9). furthermore, these investigations have revealed the lower efficacy of ultrasonography in diagnosis of aa in cases whose aa had been already diagnosed using other imaging modalities. the use of ct has been approved for assessment of cases suspected of aa with results showing decreased healthcare costs and fewer unnecessary surgical interventions. on the other hand, it should be noted that use of ct scan is accompanied with ionizing radiation, which is worrying during pregnancy (10). due to availability, not causing radiation, and its better visualization of appendix compared to ultrasonography, magnetic resonance imaging (mri) is being increasingly recommended as an alternative for assessment of pregnant cases with acute abdominal pain and inconclusive ultrasonography imaging. several investigations have shown ∗corresponding author: mehrdad farrokhi; men’s health and reproductive health research center, shohadaye tajrish hospital, tehran, iran. email: dr.mehrdad.farrokhi@gmail.com, phone number: +989384226664, orcid: 0000-0002-1559-2323. that mri has an appropriate diagnostic performance for visualizing appendix during pregnancy (11). however, these studies were conducted in different medical centers and due to the difference in training and experience of mri readers and also the quality of imaging, there is a wide range of diagnostic accuracy in the literature. therefore, in this metaanalysis, we aimed to investigate the accuracy of mri in diagnosis of aa in pregnant women. 2. methods this systematic review and meta-analysis was carried out according to the guidelines of the preferred reporting items for systematic reviews and meta-analyses (prisma) statement. 2.1. search strategy two researchers (mf and ra) independently performed a comprehensive systematic literature search of electronic databases including medline, cochrane central, embase, web of science, scopus, and google scholar to identify studies that had reported accuracy of mri for diagnosis of aa in pregnant women from inception to april 1, 2022. the eligible published papers were found using the following keywords, mesh terms, and emtree (embase subjects heading) terms: acute appendicitis, appendicitis, magnetic resonance, magnetic resonance imaging, mr, mri, pregnancy, pregnant, gestational period, and right lower quadrant pain. the combination of these search terms was also assessed using the boolean operators and and or. the search strings used were “((acute appendicitis or appendicitis or right lower quadrant pain) and (magnetic resonance or magnetic resonance imaging or mr or mri) and (pregnancy or pregnant or gestational period)”. the structured search was limited to human studies, but without language restriction and was concluded when no further studies could be found. in cases where several versions of a study were identified, the most relevant and recently published study was included in our analysis. the reference list of the eligible studies was reviewed in depth to identify other relevant studies, which were not included via systematic search. 2.2. eligibility criteria diagnostic studies were deemed eligible for inclusion in the present study if they had investigated the accuracy of mri for diagnosis of aa in pregnant patients and reported the main diagnostic parameters including sensitivity, specificity, true positive (tp), false positive (fp), false negative (fn), and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e81 true negative (tn). moreover, the diagnostic gold standard for aa used by the included studies were clinical follow-up and surgical pathology. conference abstracts, reviews, metaanalyses, cases reports, cases series with less than ten cases, non-reviewed preprints, and studies that had no full text were excluded. 2.3. study selection non-duplicate relevant studies were assessed by title and abstract, and then full-text of potentially eligible studies were reviewed. the eligible studies were screened for inclusion in the meta-analysis by two independent investigators and any disagreements between them were settled through discussion with a third researcher. 2.4. data extraction and risk of bias evaluation two investigators independently extracted data from the included studies using a predesigned abstraction form on excel. the extracted data from the studies included first author, the year of publication, study country, number of patients, mean age, tp, fp, fn, tn, sensitivity, and specificity of mri for diagnosis of aa. the risk of bias of the included studies was investigated using quality assessment of diagnostic accuracy studies (quadas)-2. 2.5. statistical analysis statistical analysis was performed using meta-disc software version 1.4 and comprehensive meta-analysis software version 3. q-statistic and i2 were used to assess heterogeneity of the included studies. the pooled sensitivity, specificity, and negative likelihood ratio were investigated using random-effects model. the pooled positive likelihood ratio and diagnostic odds ratio were calculated using fixed-effects model. the forest plots and summary receiver operating characteristic (sroc) curves were used to investigate sensitivity, specificity, and accuracy of mri for diagnosis of aa in pregnant women. for the evaluation of publication bias, egger’s and begg’s tests were carried out and funnel plots were assessed. investigation of publication bias and funnel plot were performed using stata statistical software package (stata corp., college station, tx, usa) (version 17.0). 3. results 3.1. search results our systematic search through electronic databases identified a total of 525 published papers. after removing 169 duplicates, the remaining 356 papers were screened based on the title and abstract. during this stage, 285 papers did not meet the inclusion criteria. 71 papers were retrieved and evaluated for eligibility based on full text. of these, papers that had not reported diagnostic variables (including sensitivity, specificity, tp, fp, fn, and tn) or those that were not classified original diagnostic studies, such as reviews, meta-analyses, case reports, and cases series, and comments were excluded from the meta-analysis. finally, a total of 26 papers were included in the qualitative and quantitative synthesis. the prisma flowchart of the included studies is shown in figure 1. 3.2. study characteristics the baseline characteristics and diagnostic parameters of the included studies are summarized in table 1. a total of 26 diagnostic studies were included in our study with their sample size ranging from 18 to 709 cases. the included studies were published between 2013 and 2021. mean age of the studied pregnant women ranged between 25 and 32 years. the majority of the included studies were based in usa. table 2 depicts the summary of risk of bias for the included studies. 3.3. diagnostic accuracy of mri spearman rank correlation test revealed that logit of 1specificity positively correlated with logit of sensitivity (r=0.05 and p=0.80), indicating that there was no threshold effect in the meta-analysis. the heterogeneity of the results of the included studies was evaluated regarding sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. the results showed a significant heterogeneity for sensitivity, specificity, and negative likelihood ratio (i2 = 63.5%, p<0.01; i2 = 40.9%, p = 0.01; i2 = 88.2%, p<0.01, respectively). however, there was no significant heterogeneity for positive likelihood ratio and diagnostic odds ratio (i2 = 23.2%, p = 0.14; i2 = 4.5%, p = 0.39). therefore, fixed effect model was used for analysis of positive likelihood ratio and diagnostic odds ratio. sensitivity, specificity, and negative likelihood ratio were analyzed using random effect model. the pooled sensitivity and specificity of mri in diagnosis of aa in pregnant women were 0.92 (95% ci: 0.88–0.95) and 0.98 (95% ci 0.97–0.98), respectively (figure 2). the pooled positive likelihood ratio and negative likelihood ratio were 29.52 (95% ci: 21.90–39.81) and 0.10 (95% ci: 0.04-0.25), respectively (figure2). moreover, the diagnostic odds ratio of mri was 373.75 (95% ci: 211.86–659.35) (figure 2). the area under hsroc curve was 0.99, indicating that the accuracy of mri for diagnosis of aa in pregnant women is 99% (figure 3). 3.4. publication bias the funnel plot of standard error was assessed using log ors. publication bias was not found as the funnel plot was distributed symmetrically. moreover, egger’s test (p=0.68) and begg’s test (p=0.50) did not show significant publication bias for log dor (figure 4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. motavaselian et al. 4 4. discussion although many original studies have investigated the efficacy of mri for diagnosis of aa in pregnant women, there is a lack of high-level evidence such as systematic reviews and metaanalysis regarding accuracy of mri for diagnosis of aa during pregnancy. our meta-analysis revealed that sensitivity, specificity, positive likelihood ration, negative likelihood ratio, diagnostic odds ratio, and sroc of mri in diagnosis of aa in pregnant women were 0.92, 0.98, 29.52, 0.10, 373.75, and 0.99, respectively. it is commonly known that diagnostic efficacy is low at area under the sroc of 0.50-0.60, medium at 0.70-0.90, and high at greater than 0.90, with a positive likelihood ratio > 10.00 and a negative likelihood ratio < 1.00. therefore, based on the findings of our meta-analysis, mri has high diagnostic efficacy for identifying aa in pregnant women. these findings suggest that considering the possible problems of ct scan during pregnancy, including exposure of pregnant women and their fetus to ionizing radiation, mri, seems to be a promising alternative to ct scan for diagnosis of aa in pregnant women, especially in medical centers with experienced radiologists. the high diagnostic efficacy of mri may be explained by excellent soft-tissue contrast and lower effect of large body size or the experience of the technician (12). the origin of heterogeneity among included studies may be attributed to type of mri center (academic hospital and community hospital), experience of interpreter of images, and type of mri devices. in a systematic review by basaran et al. (13) five published paper related to the use of mri and three related to the use of ct scan for diagnosis of aa in pregnant women were included. similar to our meta-analysis, the findings of their included studies were compared with the results of surgical pathology. the overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of mri for diagnosis of aa in suspected pregnant cases were 80%, 99%, 22.7, and 0.29, respectively. they concluded that ct scan and mri can be used for diagnosis of aa in pregnant cases, especially when the findings of ultrasonography are inconclusive. however, it should be kept in mind that mri is preferred over ct by practitioners due to the safety of mri during pregnancy. in another systematic review and meta-analysis, duke et al. (11) performed a systematic search in pubmed and embase to find all the studies that used mri for diagnosis of aa. they included 30 studies with a total of 2665 patients. they reported that the sensitivity and specificity of mri in diagnosis of aa are 96%. furthermore, they conducted a subgroup analysis on studies that investigated use of mri in pregnant patients. the results of subgroup analysis revealed that sensitivity and specificity of mri in pregnant patients were 94% and 97%, respectively. the difference between our diagnostic parameters with those reported in the aforementioned studies may in part be clarified by the greater number of included studies in the present meta-analysis. although american college of radiology recommended mri as modality of choice for diagnosis of aa in pregnant patients, there are some critical issues that can affect the accuracy of this imaging modality (14). a recent investigation by al-katib et al. (15) has shown that type of imaging center can affect the accuracy of mri in diagnosis of aa among pregnant cases. they found that diagnostic quality of mri is higher in main centers compared to community centers. moreover, their findings revealed that visualization of appendix by radiologist in good quality mri is considerably higher than suboptimal mri. interestingly, in this study, the only case of appendicitis with non-visualized appendix on mri belonged to the group of patients with suboptimal quality of mri. it is crucial to find the source of abdominal pain during pregnancy, especially if the cause of pain is outside the appendix. previous studies have shown that ultrasonography is an accurate imaging modality for excluding gynecologic sources of right lower quadrant pain and has become increasingly used due to being non-invasive, inexpensive, safe, easy to use, portable, and widely available (16). however, in tertiary centers providing permanent mri coverage, ultrasonography can be omitted to provide fast-tracked mri for diagnosis of aa in suspected pregnant women. 5. limitations the majority of limitations of our meta-analysis are due to heterogeneity in design, experience of image reviewers, and reporting of results among the primary published papers. moreover, it should be noted that the majority of the included studies used pathological evaluation for the approval of appendicitis in cases who underwent surgery, while there are accumulating lines of evidence proposing that aa may resolve after conservative treatments. another limitation of the included studies was that in some of them, the data were collected from medical records, retrospectively. it is possible that the symptoms of some cases improved and they were discharged, but were later admitted to a different medical center with the same symptoms and underwent surgery with the diagnosis of aa. 6. conclusion this meta-analysis showed that mri has high sensitivity, specificity, and accuracy for diagnosis of aa in pregnant women and can be used as a first-line imaging modality for suspected cases of aa during pregnancy. furthermore, it should be noted that when the result of ultrasonography is inconclusive, the use of mri can reduce unnecessary appenthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e81 dectomy in pregnant patients. 7. declarations 7.1. acknowledgments the authors thank all those who contributed to this study. 7.2. authors’ contributions all authors contributed to study design, data collection, and writing the draft of the study. 7.3. funding none. 7.4. conflict of interest none. 7.5. data availability not applicable. references 1. maimaiti a, aierkin a, mahmood km, apaer s, maimaiti y, yibulayin x, et al. laparoscopic appendectomy in pregnancy with acute appendicitis: single center experience with world review. surg laparosc endosc percutan tech. 2017;27(6):460-4. 2. franca neto ah, amorim mm, nóbrega bm. acute appendicitis in pregnancy: literature review. rev assoc med bras (1992). 2015;61(2):170-7. 3. weinstein ms, feuerwerker s, baxter jk. appendicitis and cholecystitis in pregnancy. clin obstet gynecol. 2020;63(2):405-15. 4. moghadam mn, salarzaei m, shahraki z. diagnostic accuracy of ultrasound in diagnosing acute appendicitis in pregnancy: a systematic review and meta-analysis. emerg radiol. 2022;29(3):437-448. 5. kozan r, bayhan h, soykan y, anadol az, sare m, aytac ab. acute appendicitis in pregnancy: how to manage? 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abdom imaging. 2011;36(5):596-603. 34. oto a, ernst rd, ghulmiyyah lm, nishino tk, hughes d, chaljub g, et al. mr imaging in the triage of pregnant patients with acute abdominal and pelvic pain. abdom imaging. 2009;34(2):243-50. 35. pedrosa i, lafornara m, pandharipande pv, goldsmith jd, rofsky nm. pregnant patients suspected of having acute appendicitis: effect of mr imaging on negative laparotomy rate and appendiceal perforation rate. radiology. 2009;250(3):749-57. 36. vu l, ambrose d, vos p, tiwari p, rosengarten m, wiseman s. evaluation of mri for the diagnosis of appendicitis during pregnancy when ultrasound is inconclusive. j surg res. 2009;156(1):145-9. 37. israel gm, malguria n, mccarthy s, copel j, weinreb j. mri vs. ultrasound for suspected appendicitis during pregnancy. j magn reson imaging. 2008;28(2):428-33. 38. pedrosa i, levine d, eyvazzadeh ad, siewert b, ngo l, rofsky nm. mr imaging evaluation of acute appendicitis in pregnancy. radiology. 2006;238(3):891-9. 39. birchard kr, brown ma, hyslop wb, firat z, semelka rc. mri of acute abdominal and pelvic pain in pregnant patients. ajr am j roentgenol. 2005;184(2):452-8. 40. cobben lp, groot i, haans l, blickman jg, puylaert j. mri for clinically suspected appendicitis during pregnancy. ajr am j roentgenol. 2004;183(3):671-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e81 table 1: characteristics of the studies included in meta-analysis study year country sample size age (mean) tp fp fn tn sens spec ahmed et al. (17) 2021 usa 141 26 9 5 0 127 1 0.96 badr et al. (18) 2021 belgium 85 29 6 1 0 78 1 0.987 lukenaite et al. (19) 2020 lithuania 37 30.37 5 0 1 32 0.83 1 aguilera et al. (20) 2018 usa 52 25 2 0 9 41 0.18 1 kereshi et al. (21) 2018 usa 204 29 14 1 0 189 1 0.99 wi et al. (22) 2018 south korea 125 32 24 5 0 96 1 0.95 burns et al. (12) 2017 canada 63 31 11 0 2 50 0.85 1 tsai et al. (23) 2017 usa 223 28.4 13 6 1 198 0.92 0.97 darshan et al. (24) 2017 canada 42 25.5 3 3 2 34 0.6 0.92 abadi et al. (25) 2016 israel 49 na 5 1 0 43 1 0.98 al-katib et al. (15) 2016 usa 58 28 6 1 0 51 0.86 1 burke et al. (26) 2015 usa 709 27.5 61 5 2 641 0.97 0.99 konrad et al. (27) 2015 usa 114 na 16 2 0 96 1 0.98 ramalingam et al. (28) 2015 usa 102 26.2 8 6 0 88 1 0.94 theilen et al. (29) 2015 usa 171 na 12 6 1 152 0.92 0.96 fonseca et al. (30) 2014 usa 31 na 11 0 0 20 1 1 rapp et al. (31) 2013 usa 212 26 17 6 2 187 0.89 0.97 jang et al. (32) 2011 south korea 18 31.7 5 0 0 13 1 1 masselli et al. (33) 2011 italy 40 28 5 0 0 35 1 1 oto et al. (34) 2009 usa 118 24.7 9 2 1 106 0.9 0.98 pedrosa et al. (35) 2009 usa 148 29 14 2 0 132 1 0.99 vu et al. (36) 2009 canada 19 31 1 0 1 17 0.5 1 israel et al. (37) 2008 usa 33 25.6 4 0 1 28 0.8 1 pedrosa et al. (38) 2006 usa 51 28.3 4 3 0 44 1 0.94 bichard et al. (39) 2005 usa 29 25 3 0 0 26 1 1 cobben et al. (40) 2004 netherlands 12 28 3 0 0 9 1 1 sens: sensitivity; spec: specificity; tp: true positive; fp: false positive; fn: false negative; tn: true negative. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. motavaselian et al. 8 table 2: quality assessment of the included studies using quadas-2 tool study risk of bias applicability concerns patient selection index test reference standard flow and timing patient selection index test reference standard ahmed et al. © © © © © © © badr et al. © © © © © © © lukenaite et al. © ? ? © © © © aguilera et al. © © © © © © © kereshi et al. © ? © © © © © wi et al. © ? ? © © © © burns et al. © ? ? © © © © tsai et al. © © © © © © © darshan et al. © © © © © © © abadi et al. © © © © © © © al-katib et al. © © © © © © © burke et al. © © © © © © © konrad et al. © © © © © © © ramalingam et al. © § ? ? © © © theilen et al. © ? © © © © © fonseca et al. © § ? © © © © rapp et al. § ? © © © © © jang et al. © © © © © © © masselli et al. ? § ? © © © © oto et al. © © © © © © © pedrosa et al. © © © © © © © vu et al. © © © © © © © israel et al. © © © © © © © pedrosa et al. © § © © © © © bichard et al. © § © © © © © cobben et al. © © © © © © © ©: low risk; §: high risk; ?: unclear risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e81 figure 1: prisma flowchart of the literature search and selection of studies that reported accuracy of magnetic resonance imaging (mri) for diagnosis of acute appendicitis in pregnant women. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. motavaselian et al. 10 figure 2: forest plot of the pooled sensitivity, specificity, positive likelihood ratio (lr), negative lr, and diagnostic odds ratio (or) of magnetic resonance imaging (mri) for diagnosis of acute appendicitis in pregnant women. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e81 figure 3: hierarchical summary receiver-operating characteristic (hsroc) curve indicating accuracy of magnetic resonance imaging (mri) for diagnosis of acute appendicitis in pregnant women. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. motavaselian et al. 12 figure 4: funnel plot of publication bias for the included studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e17 or i g i n a l re s e a rc h long-term complications of covid-19 in nursing staff; a retrospective longitudinal study koorosh etemad1,2, hossein hatami3, mahnaz nikpeyma4, forough mowla5, fatemeh fallah atatalab6∗ 1. department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of public health, school of public health and safety and environmental and occupational hazards control research center, shahid beheshti university of medical sciences, tehran, iran. 4. hospital infection prevention and control expert, shahid beheshti university of medical sciences, tehran, iran. 5. faculty of nursing, shahid beheshti university of medical sciences, tehran, iran. 6. school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 9 january 2023 abstract: introduction: although the lungs are the main target of coronavirus disease (covid-19), infection is also associated with a high rate of extra-pulmonary complications. this study aimed to evaluate the one-year incidence of long-term covid-19 complications among the nursing staff. methods: this study is a retrospective longitudinal study. all nursing staff working in public hospitals affiliated with shahid beheshti university of medical sciences who had been affected with covid-19 were included in the study via convenience sampling method. the patients were recruited from 20th february 2020 to 20th march 2021. results: 1762 nursing staff with a mean age of 35.08 ± 8.02 (range: 22-66) years were studied (73.5% female). the results showed that among those who reported at least one type of complication, the duration of complications was significantly longer than 1 week and the median was 8 weeks. the findings demonstrated that complications occurred in 65% of infected females. for men, this rate was 62.3%. generalized pain, anxiety disorders, and skin complications were among the complications that were significantly more common in women than in men. additionally, the incidence of anosmia, ageusia, anxiety disorders, and skin complications was significantly higher in younger people than in older people. the comparison of complications revealed that nurses were significantly more likely than other occupations to experience respiratory complications, anosmia and ageusia, generalized pain, and skin complications and that outpatients experienced significantly more complications than hospitalized patients. conclusion: the one-year cumulative incidence of long-term complications in nursing staff with covid-19 was 64.3%. the most common complications were respiratory complications, generalized pain, anosmia, and ageusia, respectively. keywords:covid-19; coronavirus; nursing staff; hospitals; long-term care cite this article as: etemad k, hatami h, nikpeyma m, mowla f, fallah atatalab f. long-term complications of covid-19 in nursing staff; a retrospective longitudinal study. arch acad emerg med. 2023; 11(1): e17. https://doi.org/10.22037/aaem.v11i1.1785. 1. introduction coronavirus disease (covid-19) is an infectious disease caused by an emerging coronavirus (sars-cov-2) (1). it is a critical global disease that continues to infect millions of people worldwide (2,3). the first case of covid-19 was announced in wuhan, china in late december 2019, and the disease has since shaken the entire world (2,4). in the second ∗corresponding author: fatemeh fallah atatalab; school of public health and safety, daneshjoo blvd., evin ave., tehran, iran. postal code: 1983535511, email: fallahniloufar@yahoo.com, tel: 0098-21-22432040-41, orcid: https://orcid.org/0000-0003-4455-1536. half of april 2022, there were reportedly 506 million cases affected worldwide, and more than 6 million people had perished as a result of this deadly illness (5). over 147,000 people have died and about 7 million cases have been identified in iran during this time (6). the initial goal of treatment for patients with covid-19 is survival (7). despite the fact that the lungs are the primary target and the symptoms are mostly systemic or respiratory, the infection is also linked to a high rate of extra-pulmonary complications that may cause disability and delayed mortality (3,4,7). there are also neurological complaints such as loss of sense of smell and taste, change in consciousness, headache, seizures, and numbness of the limbs (3). other problems such as involvement of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 2 respiratory system, cardiovascular system, kidneys, liver, endocrine glands, digestive, central nervous system, skin, eyes, and blood coagulation problems, and electrolyte imbalance have been observed (8). complications of thromboembolism caused by covid-19, such as pulmonary embolism, stroke, and other minor strokes, can also cause a wide range of permanent organ damage (7). the virus is thought to aggravate the problems of patients with heart failure. in addition, there have been numerous reports of high rates of acute myocardial infarction, arrhythmia, hypotension, and tachycardia, and other cardiovascular diseases in patients admitted to the intensive care unit due to covid-19 (4). new data as well as prior experience with other severe respiratory diseases and intensive care syndrome suggested the possibility of post-covid-19 syndrome, despite the fact that there is not yet enough information to draw a firm conclusion. these complications include a set of physical, cognitive, and psychological disabilities that can occur in those who survive a serious illness. patients with severe manifestations of covid-19 often progress to acute respiratory distress syndrome (ards) and require a ventilator. acute respiratory distress syndrome may cause permanent fibrosis in the lung tissue, resulting in respiratory problems that persist for a long time after recovery (7). studies on sars-cov-1 and middle east respiratory syndrome (mers) show that some people do not return to normal health after infection and can experience long-term health problems, including neuropsychiatric complications such as headache, fatigue, dizziness, memory loss, confusion, and difficulty concentrating and slow processing years after acute infection (3). the results of a study on patients with sars showed that more than a third of them had moderate to severe depression and anxiety up to one year after physical recovery. the mental health effects of covid-19 may also be exacerbated by loneliness and isolation, job loss and economic consequences, and increased childcare and family responsibilities (7). one group at risk of covid-19 are health professionals. it is globally advised to protect health workers through provision of personal protective equipment, training, fatigue relief, and coping with psychosocial consequences (9), due to the high burden of disease. considering that comprehensive awareness of these complications helps healthcare providers pay attention to these complications and to diagnose and treat them in a timely manner; the aim of this study was to determine the one-year incidence of long-term complications of covid-19 among the nursing staff of centers affiliated to shahid beheshti university of medical sciences in 2021. 2. methods 2.1. study design and settings this study is a retrospective longitudinal study. the nursing staff with covid-19 who worked in hospitals affiliated to shahid beheshti university of medical sciences, tehran, iran, and had long-term complications (with a duration from 1 week to 54 weeks) were recruited from 20th february 2020 to 20th march 2021. participants received an invitation letter with a checklist and consent form to participate in this study. this study received an ethics code (ir.sbmu.phns.rec.1400.081) from shahid beheshti university of medical sciences and researchers adhered to helsinki declaration’s recommendations. 2.2. participants the target population (sampling frame) included all categories of nursing services (nurse, supervisor, assistant nurse, assistant practical nurse, practical nurse, surgical technician, anesthesia technician, and midwife) working in the hospitals affiliated to shahid beheshti university of medical sciences, who were affected by covid-19, as diagnosed via polymerase chain reaction (pcr) or chest computed tomography (ct) or clinical signs of the disease. we did not take into account complications that lasted less than one week (short-term complications) or more than 54 weeks (suspected permanent complications). the sampling method was convenience sampling. 2.3. data gathering data collection was done using a checklist of 22 longterm complications (fatigue, cough, breath shortness, anosmia/ageusia, headache, body/joint pain, diarrhea/nausea, chest pain, stomachache, confusion, sleep disorder, paramnesia, concentration disorder, tachycardia, palpitation, depression, anxiety, skin rash, hair loss, hypotension, flank pain) generated by searching reputable websites such as who and cdc. the checklist had 4 sections including demographic variables (4 questions), diagnosis (3 questions), treatment (2 questions), and complications (2 questions). then checklist was sent to all educational and treatment hospitals (20 hospitals) as an official letter and in each hospital, the required data was provided by the nursing staff completely voluntarily and with their own consent. we received 18 hospital reports out of the 20. complications that lasted from one week to 54 weeks were categorized as long-term complications, and their incidence was calculated. 2.4. statistical analyses finally, the data was entered into spss 16 and analyzed. mean and percentage were used for descriptive analysis of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e17 the data. the ratio between the number of patients who reported a specific complication in a given period of time and the total number of patients who developed covid-19 in the same period was calculated to determine the incidence of the complication. to calculate the significant relationship between variables we used the chi-squared test. 3. results in this study, 1762 nursing staff members (73.5% female) with a mean age of 35.08 ± 8.02 (range: 22-66) years were examined. table 1 lists the baseline characteristics of the cases that were examined. between the ages of 20 and 40, 70% were infected. 1162 people (65.94 percent) reported at least one type of complication. the findings showed that the median length of complications among those who reported at least one type was 8 weeks and that the duration of complications was significantly longer than 1 week (p < 0.0001). 12 percent of them also experienced complications that lasted longer than six months. it is impossible to make a judgment in this regard, because the complication was still present at the time of the study in 9.23% of the patients. also, the durability of complications in those aged over 30 years was significantly more than 2 weeks (p = 0.005) and in ages under 45 years, it was significantly more than 4 weeks (p = 0.05). the findings revealed that complications affected 65% of the infected women. for men, this rate was 62.3%. those aged 40 to 50 years were more affected (70.3%), while those aged 50 to 60 years were less affected (53.1%). also, the incidence of complications was higher in supervisors (75.9%) and lower in practical nurses (41%). regarding complications, the incidence of generalized pain, anxiety disorders, and skin complications was significantly higher in women than in men. also, the incidence of anosmia & ageusia, anxiety disorders, and skin complications were significantly higher at younger ages than at older ages. the comparison of complications revealed that nurses were significantly more likely than to experience respiratory complications, anosmia and ageusia, generalized pain, and skin complications; additionally, outpatients experienced significantly more complications than hospitalized patients. table 2 shows more information. 4. discussion healthcare workers have been severely affected by the covid-19 outbreak, with many becoming infected on the job and a significant number dying. this study looked at the long-term complications of covid-19. in the current study, 1762 covid-19 personnel took part, and 1162 of them reported at least one type of complication, with a cumulative annual incidence of the complication of 64.3%. of the patients, 57.3% were nurses, 74.3% were female, and over 70% table 1: baseline characteristics of studied participants variables frequency (%) gender female 1310 (74.3) male 452 (25.7) age groups (year) 20-30 627 (35.6) 30-40 703 (39.9) 40-50 337 (19.1) 50-60 81 (4.6) 60-70 1 (0.1) missing 13 (0.7) job position nurse 1010 (57.3) supervisor 79 (4.5) assistant practical nurse 216 (12.3) practical nurse 40 (2.3) surgical technician 111 (6.3) midwife 64 (3.6) assistant nurse 38 (2.2) anesthesia technician 117 (6.6) missing 87 (4.9) method of diagnosis pcr 705 (40.0) chest ct scan 164 (9.3) clinical findings 199 (11.3) combination of two or three methods 689 (39.3) pcr: polymerase chain reaction; ct: computed tomography. were between the ages of 20 and 40. seventy-five percent (773 patients) of those who reported at least one complication had complications for at least 12 weeks. the most common complications among nurses were respiratory (52.1%), general pain (26.0%), anosmia and ageusia (14.6%), anxiety disorders (11.2%), skin complications (8.8%), and gastrointestinal symptoms (6.0%). sua´rez-garcı´a et al. performed a study in madrid (spain) and found that a total of 11.1% of health care workers (hcws) had microbiological confirmation of covid-19. the median age was 42 years (interquartile range (iqr): 34–52), and 171 (80.3%) cases were women (10). out of the 16,912 hcws who were tested for covid-19 infection in qatar, 10.6 percent of the results were positive. the median age was 39 years (iqr: 33-48) and nurses and midwives had the highest number of infections (33.2% of all infected hcws), and in contrast to our study, 65.6% of the cases were male (11). zheng et al. obtained details on 2457 cases of infection among hcws in wuhan, china. nurses made up more than half of the infected people (52.06 percent), and female hcws made up 72.28% of the cases (12). in a systematic review study, infection and mortality of covid-19 in hcws were estimated from a global perspective in the early stages of the epidemic. a total of 152,888 infections and 1,413 deaths were reported. infections were mainly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 4 table 2: distribution of long-term covid-19 complications among the nursing staff based on the demographic variables variables complications respiratory anosmia pain gi anxiety skin gender female 618 (47.2) 168 (12.8) 345 (26.3) 68 (5.2) 147 (11.2) 125 (9.5) male 213 (47.1) 43 (9.5) 94 (20.8) 21 (4.6) 33 (7.3) 10 (2.2) p-value 0.98 0.06 0.01 0.64 0.01 <0.001 age group (year) 20-30 291 (27.6) 70 (11.2) 173 (11.2) 38 (6.1) 37 (5.9) 36 (5.7) 30-40 324 (21.8) 76 (10.8) 153 (11.2) 29 (4.1) 72 (10.3) 54 (7.7) 40-50 176 (27.9) 60 (17.8) 94 (17.2) 19 (5.6) 59 (17.5) 39 (11.6) 50-60 37 (19.8) 5 (6.2) 16 (11.2) 3 (3.7) 10 (12.5) 5 (6.2) 60-70 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) p-value 0.3 0.001 0.05 0.53 0.001 0.02 job position nurse 526 (52.1) 147 (14.6) 263 (26.0) 61 (6.0) 113 (11.2) 89 (8.8) supervisor 45 (57.0) 16 (20.3) 32 (40.5) 4 (5.1) 14 (17.7) 14 (17.7) assistant practical nurse 101 (46.8) 18 (8.3) 62 (28.7) 9 (4.2) 16 (7.4) 11 (5.1) practical nurse 13 (32.5) 1 (2.5) 4 (10.0) 1 (2.5) 3 (7.5) 2 (5.0) surgical technician 39 (35.1) 8 (7.2) 21 (18.9) 5 (4.5) 8 (7.2) 3 (2.7) midwife 28 (43.8) 8 (12.5) 20 (31.3) 6 (9.4) 9 (14.1) 6 (9.4) assistant nurse 32 (84.2) 3 (7.9) 15 (39.5) 1 (2.6) 4 (10.5) 2 (5.3) anesthesia technician 47 (40.2) 10 (8.5) 22 (18.8) 2 (1.7) 13 (11.1) 8 (6.8) p-value 0.001 0.001 0.001 0.32 0.22 0.001 hospitalization history hospitalization 113 (65.7) 20 (11.6) 73 (42.4) 20 (11.6) 42 (24.6) 28 (16.3) outpatient 718 (45.2) 191 (12.0) 366 (23) 69 (4.3) 138 (8.7) 107 (6.7) p-value 0.001 0.87 0.001 0.001 0.001 0.001 data are presented as frequency (%). gi: gastrointestinal. in women (71.6%, n = 14058) and nurses (38.6%, n = 10.706). the reported infected hcws had an average age of 47.3 years, with a range of 18 to 84. africa reported the fewest covid19 infections among hcws (1472, 1.0%), while europe reported the most (119628, 78.2%). on 8 may 2020, spain reported the highest cumulative number of covid-19 infections in hcws worldwide with 30,663 (20% of all hcw infections), italy (23718), and the netherlands (13884) followed (13). according to the study by chutiyami et al. the overall infection rate among healthcare workers ranged from 3.9% to 11%. female healthcare workers (71.6%) had higher rates of infection than male healthcare workers. the number of cases (4812 from 14058) was higher in the age group of 50 to 59 years and nurses were the most affected group among health care professionals. cough, fever, headache, and malaise were the main clinical symptoms experienced by healthcare workers. the most important symptoms associated with covid19 infection were anosmia, fever, myalgia, fatigue, and sore throat (14). the total number of patients among healthcare workers who were examined in 28 studies for a meta-analysis study was 119,883. in hcws with covid-19, fever was the most common symptom, followed by cough and fatigue, with a mean age of 38.37 years and a female prevalence of 78.6% (15). gómez-ochoa et al. estimated that the prevalence of sarscov-2 infection in healthcare worker samples, using reverse transcription polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (ci): 7.15) and 7% (95% ci: 4.11), respectively. the most affected staff were nursing staff (48%, 95% ci: 41, 56). fever, anosmia, and myalgia were the main factors associated with sars-cov-2 infection (16). among the symptomatic hcws for covid19, the most commonly reported symptoms were fever (57%) and dry cough (57%) followed by nausea (43%) and myalgia (48%). the study by magnavita et al. showed that the infected workers were mainly nurses and young people. the most common symptoms observed in infected workers were muscle pain (52.4%) and fatigue (47.6%). anosmia (42.7%) and ageusia (37.8%) were also very common among infected hcws (17). the high rate of infection among nursing staff may be related to the nature of nursing responsibilities, including 24-hour care of infected patients. additionally, some nurses working in the healthcare sector are primarily concerned with screening patients and are, therefore, exposed to sars-cov-2 before their diagnosis is confirmed. in addition to the potential severity of acute covid-19, persistent symptoms may last for months and can be significantly debilitating. hcws, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e17 like other people infected with covid-19, may experience a long-term illness. there are few reports of long-term consequences for hcw survivors of covid-19 studies. in a prospective cohort study of admitted patients in norway, half reported dyspnea, and one quarter had reduced gas transfer on lung function tests 3 months after the initial infection (18). organ systems other than the respiratory system are also affected by covid-19, including the cardiovascular and musculoskeletal systems, and these effects can be sustained. more than two months after the initial covid-19 infection, a sizable portion of patients still had a myocardial infarction, as determined by magnetic resonance imaging (mri), including numerous patients who were either asymptomatic during the initial illness or only had mild symptoms (19). a systematic review and meta-analysis showed that 80% of people with confirmed covid-19 diagnosis still had at least one overall effect beyond 2 weeks after acute infection. fatigue, anosmia, pulmonary dysfunction, abnormal chest xray/ct, and neurological disorders were the most common. the five most common complications were: fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%) (20). in a study by townsend et al., of the 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (128.67; 52.3%) at an average of 10 weeks after the onset of the symptoms of covid-19 (21). a qualitative study in the uk examined the perspectives of people who experienced persistent symptoms after covid-19 infection. some people who had an allegedly minor covid-19 infection were still dealing with cyclical symptoms that persisted, including pain, palpitations, shortness of breath, memory loss, and fatigue (22). in a follow-up study conducted in china, among non-critical cases of hospitalized patients with covid-19, radiographic changes persisted in approximately two-thirds of patients 3 months after discharge. following a 3-month follow-up, the following symptoms were present: exertional dyspnea (14.55 percent), cough and sputum (1.81 percent), headache (18.18 percent), fatigue (16.36 percent), and gastrointestinal (gi) symptoms (30.91 percent) (23). xiong et al. examined the prevalence and clinical symptoms of possible post-traumatic stress disorder (ptsd) in surviving hcws 6 months after the outbreak of covid-19 in china. the mean age of the 291 studied surviving hcws was 37.3 years, 81.1% were female, 58.4% were nurses, and 19.9% of them had possible ptsd 6 months after acute exposure to covid-19. factors significantly associated with possible ptsd included lifethreatening covid-19, intensive care unit (icu) admission, increased respiratory symptoms, exposure to other traumatic events, a residual symptom of dizziness, and residual symptom of shortness of breath (24). in one study, liao et al. evaluated the long-term consequences of covid-19 among hcws in china. they observed decreased lung diffusion function, abnormal ct patterns, impaired physical function, and psychiatric disorders during the 1-year follow-up. a pulmonary diffusion abnormality was found 1 year after discharge in 40.97% of hcws who survived mild/moderate covid-19 and 47.67% of hcws who survived severe/critical covid-19, according to the lung function assessment. an abnormal ct pattern was also found in 37.5% of the hcws. probable ptsd was reported in 21.9% of the surviving hcws. the proportion of nurses and females among infected hcws was high. recently, anosmia and ageusia emerged among the earliest symptoms of sarscov-2 infection, possibly due to a disruption of the ciliary nasal epithelium mediated by the novel coronavirus (25). failure to address infection among hcws has the potential to increase transmission of covid-19 in healthcare centers and communities. hcw deficiency may impair the quality of national health care services, both in the acute phase of the epidemic and in the long term. immediate intervention in the form of effective protective measures, early diagnosis, immediate treatment, and vaccination are essential. healthcare workers experienced considerable covid-19related physical health issues. this requires targeted interventions and multidisciplinary teams to develop preventive measures, rehabilitation techniques, and clinical management strategies to support and address the long-term care of healthcare workers with covid-19. 5. limitations the fact that participation in the study was voluntary makes it impossible to differentiate if those who opted out did not have covid-19, experience complications, or simply did not want to participate in the study. another drawback was that a lot of the complications were based on people’s individual perceptions, making it impossible to assume that everyone understood them accurately. we also only got 18 hospital reports out of 20. this might be a confounding factor, so we advise controlling it through systematic sampling in future studies. 6. conclusions the one-year cumulative incidence of long-term complications among nursing staff with covid-19 was 64.3%. the most common complications were respiratory complications, generalized pain, anosmia, and ageusia, respectively. 7. declarations 7.1. acknowledgments we appreciate each and every participant who helped us with the data collection and questionnaire distribution. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 6 7.2. conflict of interest the authors have no conflict of interest to declare 7.3. fundings and supports this study was supported by shahid beheshti university of medical sciences under number 29375. 7.4. authors’ contribution all authors participated in data collection, data analysis, manuscript preparation, and final manuscript approval. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. references 1. world health organization (who). coronavirus [internet]. world health organization (who). 2021 [cited 2021 mar 23]. available from: https://www.who.int/healthtopics/coronavirus#tab=tab_1 2. hirawat r, saifi ma, godugu c. targeting inflammatory cytokine storm to fight against covid-19 associated severe complications. life sci [internet]. 2021;267(october 2020):118923. available from: https://doi.org/10.1016/j.lfs.2020.118923 3. sun b, tang n, peluso mj, iyer ns, torres l, donatelli jl, et al. characterization and biomarker analyses of postcovid-19 complications and neurological manifestations. 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journal of epidemiology. 2021;190(1):161-75. 17. magnavita n, tripepi g, di prinzio rr. symptoms in health care workers during the covid-19 epidemic. a cross-sectional survey. international journal of environmental research and public health. 2020;17(14):5218. 18. lerum tv, aaløkken tm, brønstad e, aarli b, ikdahl e, lund kma, et al. dyspnoea, lung function and ct findings 3 months after hospital admission for covid-19. european respiratory journal. 2021;57(4). 19. smallwood n, harrex w, rees m, willis k, bennett cm. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e17 covid-19 infection and the broader impacts of the pandemic on healthcare workers. respirology. 2022. 20. lopez-leon s, wegman-ostrosky t, perelman c, sepulveda r, rebolledo pa, cuapio a, et al. more than 50 longterm effects of covid-19: a systematic review and metaanalysis. scientific reports. 2021;11(1):1-12. 21. townsend l, dyer ah, jones k, dunne j, mooney a, gaffney f, et al. persistent fatigue following sars-cov-2 infection is common and independent of severity of initial infection. plos one. 2020;15(11):e0240784. 22. kingstone t, taylor ak, o’donnell ca, atherton h, blane dn, chew-graham ca. finding the’right’gp: a qualitative study of the experiences of people with long-covid. bjgp open. 2020;4(5). 23. zhao y-m, shang y-m, song w-b, li q-q, xie h, xu qf, et al. follow-up study of the pulmonary function and related physiological characteristics of covid-19 survivors three months after recovery. eclinicalmedicine. 2020;25:100463. 24. xiong l-j, zhong b-l, cao x-j, xiong h-g, huang m, ding j, et al. possible posttraumatic stress disorder in chinese frontline healthcare workers who survived covid-19 6 months after the covid-19 outbreak: prevalence, correlates, and symptoms. translational psychiatry. 2021;11(1):1-6. 25. liao t, meng d, xiong l, wu s, yang l, wang s, et al. longterm effects of covid-19 on health care workers 1-year post-discharge in wuhan. infectious diseases and therapy. 2022;11(1):145-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references emergency. 2017; 5 (1): e74 le t t e r to ed i to r traumatic brain injury is unlikely precipitating leigh syndrome due to the gjb2 mutation c.35delg josef finsterer1∗, sinda zarrouk-mahjoub2 1. krankenanstalt rudolfstiftung, vienna, austria. 2. university of tunis el manar and genomics platform, pasteur institute of tunis, tunis, tunisia. received: march 2017; accepted: june 2017; published online: 30 june 2017 cite this article as: finsterer j, zarrouk-mahjoub s. traumatic brain injury is unlikely precipitating leigh syndrome due to the gjb2 mutation c.35delg. emergency. 2017; 5(1): e74. dear editor: with interest we read the article by ashrafi et al. about a 14-year-old female who is regarded to have developed leigh syndrome (ls) after traumatic brain injury (tbi) (1). we have the following comments and concerns: we do not agree with the notion that traumatic brain injury was the precipitating factor for ls. the patient had a history of hypoacusis, which is a typical clinical manifestation of a mitochondrial disorder (mid). hypoacusis obviously had developed long before the tbi. additionally, the patient was diagnosed with neuropathy of the peripheral nerves two months after tbi. it is rather unlikely that neuropathy was triggered by tbi and more likely it was already present before the trauma. thus, the initial manifestations of ls in the presented patient were most likely hypoacusis followed by neuropathy and tbi only might have triggered the seizure but not the mid. why was the patient put on phenytoin, which is well-known to be mitochondrion-toxic (2)? phenytoin may worsen epilepsy and mid in general and it is conceivable that in fact phenytoin was responsible for worsening of the phenotype and not the tbi. in a 16-year-old female with melas syndrome due to the mutation m.3243a>g, phenytoin caused intestinal pseudo-obstruction one month after intravenous phenytoin for status epilepticus (3). in a patient with kearns-sayre syndrome phenytoin decreased cerebrospinal fluid (csf) folate levels (4). in rat hepatocytes, phenytoin increased reactive oxygen species (ros) formation, decreased intracellular reduced glutathione, increased intracellular oxidised glutathione, and enhanced lipid peroxidation and mitochondrial damage (5). in a hepatic microsomal system, phenytoin decreased state-3 respiration, ∗corresponding author: josef finsterer; postfach 20, 1180 vienna, austria, europe. tel: +43-1-71165-92085 / fax: +43-1-4781711 / e-mail: fipaps@yahoo.de atp synthesis, and the mitochondrial membrane potential. in this model, phenytoin increased state-4 respiration, impaired ca++-uptake and release, and inhibited ca++-induced swelling (6). it would be interesting to know how the gjb2 mutation was detected. was whole exome or panel sequencing carried out? did the authors choose a gene by gene sequencing approach? did the parents undergo genetic investigations? did each of them carry the mutation in the heterozygous state? did either of the parents manifest clinically? we should be informed about the exact sequence of the tbi. is it conceivable that the fall was already due to a seizure or syncope? was the patient unconscious after the tbi? the authors mention that basal ganglia lesions were “negative” on dwi (1). however, basal ganglia appear hyperintense on dwi in figure 2. what was the cause of respiratory insufficiency at the second admission? was it attributable to the cerebral lesions, to myopathy affecting the respiratory muscles, to lactic acidosis, or to a pulmonary infection? simultaneous application of a bunch of drugs is not advisable since it cannot be differentiated which of them is effective in case the administration is followed by a beneficial response. overall, the report is not convincing with regard to tbi as the precipitating factor of ls. most likely, worsening of ls was a random event or triggered by phenytoin. it is also conceivable that stress from tbi triggered the production of ros, which were mitochondrion-toxic to such a degree that a previously subclinical condition became gradually symptomatic. references 1. ashrafi f, pakdaman h, arabahmadi m, behnam b. head trauma as a precipitating factor for late-onset leigh syndrome: a case report. emergency. 2017;5(1):e43. 2. finsterer j. toxicity of antiepileptic drugs to mitochondria. 2016. 3. chiyonobu t, noda r, yoshida m, fujiki a, ishii r, nukthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com j. finsterer and zarrouk-mahjoub s 2 ina s, et al. intestinal pseudo-obstruction in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (melas) associated with phenytoin therapy. brain and development. 2008;30(6):430-3. 4. allen rj, dimauro s, coulter dl, papadimitriou a, rothenberg sp. kearns-sayre syndrome with reduced plasma and cerebrospinal fluid folate. annals of neurology. 1983;13(6):679-82. 5. eghbal ma, taziki s, sattari mr. mechanisms of phenytoin-induced toxicity in freshly isolated rat hepatocytes and the protective effects of taurine and/or melatonin. journal of biochemical and molecular toxicology. 2014;28(3):111-8. 6. santos n, medina w, martins n, mingatto fe, curti c, santos a. aromatic antiepileptic drugs and mitochondrial toxicity: effects on mitochondria isolated from rat liver. toxicology in vitro. 2008;22(5):1143-52. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references archives of academic emergency medicine. 2023; 11(1): e12 or i g i n a l re s e a rc h dizziness evaluation and characterisation of patients with posterior circulation stroke in the emergency department; a case series study miguel saro-buendía1,2∗, lidia torres-garcía1,2, natalia jaramillo angel1, raúl mellídez acosta1, javier cabrera guijo1, catalina bancalari díaz1, alfonso garcía piñero1, vanesa pérezguillén1, miguel armengot carceller1,2 1. unit of otoneurology, department of otorhinolaryngologyhead and neck surgery, la fe university and polytechnic hospital, spain. 2. department of surgery, university of valencia, spain. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: dizziness is a common scenario in the emergency departments (eds). among dizziness underlying causes, the posterior circulation stroke is especially relevant due to its mobimortality and concerning misdiagnosis rates. therefore, we conducted this study to assess dizziness evaluation and baseline characteristics of patients with ps in the ed. methods: we conducted a 3-year retrospective observational study on ps cases confirmed by magnetic resonance imaging (mri). concretely, we analysed the demographic profile of these patients, the initial ps clinical presentation, and diagnostic workup (with emphasis on dizziness evaluation) performed at the ed. results: during the study period, 85 cases were registered. risk factors for cardiovascular disease were present in 85.5% and previous visits to the ed due to dizziness were recorded in 16.5%. the main clinical presentation was dizziness, concretely as an acute vestibular syndrome (38.8%) with additional neurological signs or symptoms (80%). evaluation by the otolaryngologist on call was requested in less than 10% of the cases and included the hints protocol use with a sensitivity of 100% for central nervous system underlying causality. a brain ct study was always performed with a sensitivity of 27%. however, 96.47% of patients were primarily admitted to the neurology hospitalization ward and mri was always performed in a mean time of 3.21 days confirming the diagnosis. conclusion: dizziness is the most frequent symptom of ps. patients usually present an avs (associated with additional n-ss or not) and hints bedside examination is the most adequate protocol to differentiate a ps from other avs causes until the diagnostic confirmation via mri. interestingly, mainly otolaryngologists seem to use hints. however, the use of ct is widespread despite its poor value. keywords: brain infarction; vestibular diseases; vertigo; emergency medicine cite this article as: saro-buendía m, torres-garcía l, jaramillo angel n, mellídez acosta r, et al. dizziness evaluation and characterisation of patients with posterior circulation stroke in the emergency department; a case series study. arch acad emerg med. 2023; 11(1): e12. https://doi.org/10.22037/aaem.v11i1.1764. 1. introduction dizziness constitutes the main complaint of approximately 3% of the emergency department (ed) medical consultations (1). the underlying cause is usually a vestibular condition but might be a severe central nervous system (cns) disorder. among cns disorders, the most frequent is the posterior circulation stroke (ps) (2). ∗corresponding author: miguel saro-buendía; fernando abril martorell 106, valencia 46026, spain. email: msarobuendia@gmail.com. phone number: (+34) 961244016, orcid: https://orcid.org/0000-0003-4794-3615. specifically, the ps-associated dizziness usually corresponds to an acute vestibular syndrome (avs), which consists of an abrupt monophasic dizziness associated with nausea or vomiting, gait instability, spontaneous nystagmus, and intolerance to cephalic movements (3). the most frequent cause of avs is an acute unilateral vestibular loss (uvl) whose course is benign and self-limited. nonetheless, the second cause (around 5 to 10% of the cases) is the ps, with the posterior inferior cerebellar artery (pica) territory being the most frequently affected (2-4). an avs constitutes a diagnostic challenge because it is usually not associated with additional neurological signs or symptoms (n-ss), even when a ps is the underlying cause this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index m. saro-buendía et al. 2 (3). kerber et al. in 2006 observed that one-third of the ps had initially been misdiagnosed (5). a more recent study describes a 37% rate of early ps misdiagnosis, whereas there is only a 16% misdiagnosis rate for anterior circulation strokes (4). in the ed diagnostic workup, physical examination is essential, the hints (head impulsenystagmus-test of skew) protocol being the main component. it consists of a three-step bedside oculomotor examination and includes the vestibuloocular reflex study in the head impulse test (hit), careful eye movement assessment to identify nystagmus, and the test of skew to identify vertical ocular misalignment. this protocol appears to have higher sensitivity (100%) and specificity (96%) for ps diagnosis than an mri diffusion-weighted imaging in the first 48 hours since clinical onset. moreover, in this early context, the mri has a false negative rate up to 20% for ps, which might contribute to misdiagnosis (3, 6). ct scan is performed in more than 50% of the avs cases, even if evidence discourages its use (7). in this context, ct scans have low sensitivity (approximately 7%) for ps, even lower than the 40% shown for anterior circulation strokes (8, 9). an indication for a ct scan is the suspicion of brain haemorrhage. however, this entity is rarely presented as an isolated avs (10). given that ps misdiagnosis is relevant to the patients’ prognosis and dizziness is a common scenario in the ed, we feel encouraged to conduct this research (11, 12). the aim of the study is to contribute to a better understanding of this entity to reduce initial ps misdiagnosis rates in the future. 2. methods 2.1. study design and settings we designed a case series observational study to characterize the initial evaluation of patients with confirmed ps diagnosis. we studied the demographic profile, clinical presentation, and diagnostic workup features (with emphasis on the evaluation of dizziness) of these patients from the ed admission to ps diagnostic confirmation. we recruited cases of ps confirmed by mri diffusion-weighted imaging in our institution from april 2018 to april 2021. the project follows the principles outlined in the declaration of helsinki and was approved by the ethics committee of our institution (ceib; register code 2022-091-1). 2.2. participants inclusion criteria adults ≥ 18 years of age. posterior circulation stroke confirmed by mri diffusionweighted imaging. exclusion criteria less than 18 years of age. other cases of possible/ probable posterior circulation stroke not confirmed by mri including: patients who died before an mri confirmation, patients diagnosed using ct, for whom mri was not performed, and other possible cases. 2.3. data gathering radiology and clinical reports (ed visit and hospitalization period) constituted the data source of our outcome measures, including patient demographic (sex, age, cardiovascular or otoneurologic past medical history, ed visits due to dizziness in the prior 2 years, risk factors for cardiovascular disease such as diabetes mellitus, arterial hypertension, hypercholesterolemia, or smoking habits), ed visit details (main clinical complaint, blood pressure, presence of avs, impossibility to stand or sit, additional n-ss to those expected in avs, hints protocol, ct use, specialty of on-call physicians that were consulted, clinical suspicion of ps), and hospitalization period details (hospitalization ward in which the patient was admitted, initial score of national institute of health stroke scale, n-ss debuting during the hospitalization period, days to mri diagnostic confirmation, and cerebral vascular territories affected). fixed criteria were applied to ed reports to determine if the clinical presentation corresponded with an avs. these criteria included the presence of dizziness with an abrupt onset and a monophasic clinical course associated with nausea or vomiting, gait instability, spontaneous nystagmus, and intolerance to cephalic movements. potential recall bias was avoided acquiring information directly from medical reports. the study included qualitative and quantitative variables. 2.4. statistical analysis we used descriptive statistical methods such as the measurement of frequency distribution and central distribution. due to the nature of the study, no interactions were examined, and no causal inference was performed. restriction methods were applied in the selection of individuals (mri diagnostic confirmation) to control confounding factors related to misdiagnosis. the approach to the missing data was to omit cases with the missing data and analyse the remaining data (listwise deletion method). 3. results 3.1. baseline characteristics of studies cases during the study period, 85 cases of ps, confirmed by mri diffusion-weighted imaging, were registered in our institution. patients had a median age of 73 years (interquartile range from 64 to 79 years) and 64.71% were males. at least one risk factor for cardiovascular disease was present in 91.6% of the cases. history of cardiovascular disease events this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 3 archives of academic emergency medicine. 2023; 11(1): e12 was present in 38.8% and only 3.53% had previous otoneurologic disease. during the 2 years prior to the ps, 16.5% had visited the ed due to dizziness. among these patients, diagnosis in the ed discharge summary was “nonspecific dizziness” in 42.9% of the cases, “transient ischemic attack” in 28.6% and “vertigo under investigation” in 21.4%. during the ed visit, the chief complaint was “dizziness” in 38.8% of cases. another common chief complaint (15.3%) was “unsteady gait”. clinical presentation was compatible with an avs in 38.8% of patients. among these cases, around 80% presented additional n-ss and 34.1% had impossibility standing or sitting. blood pressure on ed arrival was above 180 mmhg in 22.4% of the cases. an evaluation by the otolaryngologist on call was requested in 8.24% of the patients. in the otolaryngologist evaluation, hints protocol was always applied and 100% sensitive for cns underlying causality. concretely, the hints protocol always evidenced a patent vestibulo-ocular reflex in the hit and a normal test of skew. on the other hand, nystagmus was only present in 22.4% of the cases and showed a unidirectional horizontal-torsional pattern in 47.7%. a non-contrast head ct was performed in all the patients, the resulting sensitivity for ps was 27%. 3.2. dispositions from ed after the ed initial evaluation, 96.47% of patients were admitted to the neurology hospitalization ward with an average score of 5.87 points on the national institutes of health stroke scale (nihss). the remaining 3.53% of patients were admitted to the otolaryngology or internal medicine wards. overall, new n-ss debuted during hospitalization time in 22.4% of the patients. among patients who did not present n-ss in the ed initial evaluation, these debuted during hospitalization time in 29.2%. in a mean time of 3.21 days mri diffusion-weighted imaging was performed, confirming the ps diagnosis. the basilar, vertebral, and posterior cerebral arteries were affected in a similar proportion (17.6%, 22.4% and 29.4% respectively). a vertebral artery dissection was observed in 4.7% of the cases. the pons, cerebellar hemispheres, and occipital lobes were the territories most commonly affected by ischemia 4. discussion we report dizziness as the chief complaint at the clinical onset of ps. moreover, our retrospective analysis based on fixed criteria applied to the ed reports confirmed avs as the usual presentation of ps. then, a right identification of the avs and a proper differential diagnosis among its causes should facilitate a prompt ps detection (4, 5). for years, the initial ed approach for dizziness has consisted in categorizing whether if the patient presents with vertigo, instability, presyncope or other poorly defined symptoms. this differentiation theoretically facilitates the diagnosis when used by a neurotologist. nonetheless, recently it has been demonstrated that this approach in the ed context is overrated and often leads to misdiagnosis (13). newmantoker et al. demonstrated how more than 50% of the patients change the dizziness category that represents their symptoms when asked twice within a 5to 10-minute interval (14). to unify the mentioned categories under a unique concept “dizziness” helps to emphasize in more relevant diagnostic features such as the timing and trigger patterns of their symptoms (2, 14-16). in this diagnostic paradigm, patients with dizziness are grouped into three categories: spontaneous episodic vestibular syndrome (s-evs), triggered episodic vestibular syndrome (t-evs), and avs (2, 17). in the ed context, we do recommend emphasizing on timing and the trigger pattern when evaluating a patient presenting with dizziness. this approach increases chances of avs detection, which ultimately facilitates the ps diagnosis. once an avs is identified, the differential diagnosis between the most common causes (uvl and ps) should be conducted. this step is essential as the management is very different and misdiagnosis of ps might lead to serious adverse consequences. lack of familiarity with inner ear disorders facilitates misdiagnosis (18). the demographic profile of our patients consisted mainly of males over 70 years old with cardiovascular disease risk factors. almost 40% of our patients had a history of cardiovascular disease events. the demographic profiles of ps and uvl have not been compared and therefore, we cannot conclude if they differ. the importance of demographic profile while investigating the avs causality is probably overestimated. age and risk factors for cardiovascular disease increase the pre-test probability of ps being the underlying cause. nonetheless, a study based on the cardiovascular risk scale abcd2 (which studies age, arterial pressure, unilateral motor weakness or speech impairment, duration of symptoms, and the presence of diabetes mellitus) to differentiate between ps and vl shows a 60% sensitivity for both. in the context of an avs, the capability of the hints protocol to detect a ps is superior to that of the abcd2 scale. this fact is even more evident in the evaluation of young patients (18). in the ps clinical onset, according to literature, avs is associated with absence of additional n-ss in 80% of the cases (3). however, in our study, 80% of the patients with an avs presented additional n-ss in the initial ed evaluation. moreover, these debuted during hospitalization time in 30% of those with initial absence of additional n-ss. the reason for this variability is unknown, but we emphasize that the absence of n-ss does not rule out ps as the underlying cause. in the ed context, the diagnostic relevance of the presence or absence of n-ss is probably overrated, and this fact conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index m. saro-buendía et al. 4 tributes to initial misdiagnosis (13). in our study, evaluation by the otorhinolaryngologist on call was requested in 8.24% of the cases. among these, the hints protocol was always applied, and the suspicion of a cns cause (ps being the most common) was always reported. therefore, the sensitivity of hints protocol for ps suspicion in our study was 100% and supports previous evidence (19). it has elevated cost-effectiveness and shows higher sensitivity than any other ed diagnostic approach. as a result, the hints protocol is recommended for screening patients with avs in the ed context (18). nonetheless, it has limitations such as the need for familiarity with oculomotor examination and the requirement to correctly identify an avs prior to its application (18). at our institution, physicians from diverse medical specialties receive formation about otoneurology. this fact might explain why the evaluation by otorhinolaryngologist on call was rarely requested, even when the ps debuted as an avs. also, the presence of additional n-ss in 80% of the cases might explain an elevated cns causality suspicion. nonetheless, in our study, the hints protocol was never applied by physicians who were not otorhinolaryngologists. the presence of spontaneous nystagmus was reported in 22.4% of the cases and was unidirectional with a horizontal-torsional pattern in 47.4% of the occasions. according to ed-based observational studies, the presence or absence of nystagmus is reported in more than 80% of the cases. however, the nystagmus features are usually not described and when reported, their characteristics are not coherent with the diagnosis given (20). in the initial ed evaluation, a non-contrast head ct was performed in all the patients of our study. this fact proves the systematic use of ct in the diagnostic workup of dizziness in our institution. a previous study describes the ct use in more than 50% of the patients in this clinical context as excessive (7). ct is the standard imaging technique among patients presenting with acute stroke symptoms to rule out brain haemorrhage. however, a ps due to brain haemorrhage rarely debuts as an isolated avs compared to ischemic forms of ps. therefore, given its low diagnostic rentability for ps (716% in previous studies and 27% in our study) and the rarity of brain hemorrhage presenting as an isolated avs, the ct is not recommended for the avs diagnostic workup (7-9, 21, 22). the ct implies radiation exposure, elevated costs, and a misuse of material and personal ed resources. however, the most dangerous consequence of its overuse is ps misdiagnosis due to false reassurance by a normal ct result. it is a common practice to link a normal scan with uvl as the underlying cause of an avs (13), grewal k et al. described how those with a normal ct had a double ps likelihood than those who did not receive a ct in the diagnostic workup. this fact suggests that ed physicians correctly suspect ps but incorrectly assume a ps absence when a normal ct is obtained (21). as a result, we do not recommend ct use in the initial avs evaluation unless the intention is to rule out a brain haemorrhage. in our series, the suspicion of ps or a serious neurological condition was adequate as 96.47% of the cases were admitted in the neurology hospitalization ward after the initial ed evaluation. the mean nihss score on admission was 5.87 points, which is close to the average of 3.8 points recorded in the literature (4). the unusually elevated presence of additional n-ss in the recorded avss might facilitate the ps suspicion. nonetheless, the avs presence is determined by the retrospective application of fixed criteria to the ed reports and therefore, its real incidence might be different. the increased detection of additional n-ss may be explained by the extensive clinical experience implicit to a tertiary care ed. to study retrospectively from mri-confirmed cases implies important limitations, which probably overestimate our ps identification rates. an example is the exclusion of misdiagnosed patients (both discharged or hospitalized in neurology/nonneurology wards). also, those who died prior to receiving an mri confirmation of ps were excluded. the mri diffusion-weighted imaging is the diagnostic gold standard, its use is part of the study inclusion criteria and therefore, was performed in the 85 cases in a mean time of 3.21 days since the ed admission (22). causative lesions were in the vertebral, basilar, and posterior cerebral arteries in a similar proportion. in the literature, atherosclerotic stenosis tends to occur in the extracranial vertebral artery, whereas embolic events usually affect the basilar or the intracranial vertebral arteries (23). a vertebral artery dissection was detected in 4.7% of our patients. this condition usually occurs in the extracranial portion of the vertebral artery and causes additional symptoms such as pain in the posterior part of the neck or occiput (23). 5. limitations to study retrospectively from mri-confirmed cases may overestimate ps identification rates. an example was the exclusion of misdiagnosed patients (both discharged or hospitalized in neurology/non-neurology wards). also, those who died prior to receiving an mri confirmation of ps were excluded. there is a risk of information bias in the present study, because the presence of avs was determined based on clinical criteria applied to ed reports. also, there might be selection bias, we recruited patients exclusively from a tertiary care institution. clinical evaluation might be optimized in a tertiary care institution due to the wide experience of emergency physicians and the constant presence of neurology and otolaryngology specialists on call. these facts and the implicit features of case series studies affect the external validity of our results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 5 archives of academic emergency medicine. 2023; 11(1): e12 6. conclusions patients suffering a ps usually refer to dizziness as their main symptom and present an avs (with or without additional nss). emphasis on timing and trigger patterns is key to detect an avs. bedside hints exam discerns ps from other avs causes and ed physicians (not only otolaryngologists) should explore it consistently. ct is widely used despite its poor value, but negative findings do not impede admission to get an mri-confirmed diagnosis. 7. declarations 7.1. acknowledgments we would like to express our acknowledgements to the otorhinolaryngology-head and neck surgery, neurology and emergency departments of our institution. 7.2. conflict of interest none. 7.3. fundings and supports none. 7.4. authors’ contribution miguel sarobuendía: main contributor, study conception and design, acquisition and interpretation of data analysis, draft of manuscript and preparation, final version approval; lidia torres garcía and natalia jaramillo angel: study design, acquisition and interpretation of data, draft of manuscript and preparation, final version approval; raúl mellídez acosta, javier cabrera guijo and catalina bancalari díaz: data acquisition, interpretation of data , final version approval; vanesa pérezguillén: study conception and design, interpretation of data, draft of manuscript and preparation, final version approval; alfonso garcía piñero: study conception and design, interpretation of data, english language vocabulary and grammar review, final version approval; miguel armengot carceller: study conception and design, interpretation of data, final version approval. references 1. newman-toker de, hsieh yh, camargo ca, jr., pelletier aj, butchy gt, edlow ja. spectrum of dizziness visits to us emergency departments: cross-sectional analysis from a nationally representative sample. mayo clin proc. 2008;83(7):765-75. 2. edlow ja, newman-toker d. using the physical examination to diagnose patients with acute dizziness and vertigo. j emerg med. 2016;50(4):617-28. 3. tarnutzer aa, berkowitz, al, robinson ka, hsieh yh, newman-toker de. does my dizzy patient have a stroke? a systematic review of bedside diagnosis in acute vestibular syndrome. cmaj. 2011;183(9):57192. 4. arch ae, weisman dc, coca s, nystrom kv, wira cr, 3rd, schindler jl. missed ischemic stroke diagnosis in the emergency department by emergency medicine and neurology services. stroke. 2016;47(3):668-73. 5. kerber ka, brown dl, lisabeth ld, smith ma, morgenstern lb. stroke among patients with dizziness, vertigo, and imbalance in the emergency department: a population-based study. stroke. 2006;37(10):2484-7. 6. kattah jc. use of hints in the acute vestibular syndrome. an overview. stroke vasc neurol. 2018;3(4):1906. 7. kerber ka, zahuranec db, brown dl, meurer wj, burke jf, smith ma, et al. stroke risk after nonstroke emergency department dizziness presentations: a population-based cohort study. ann neurol. 2014;75(6):899-907. 8. brazzelli m, sandercock pa, chappell fm, celani mg, righetti e, arestis n, et al. magnetic resonance imaging versus computed tomography for detection of acute vascular lesions in patients presenting with stroke symptoms. cochrane database syst rev. 2009;(4). 9. ozono y, kitahara t, fukushima m, michiba t, imai r, tomiyama y, et al. differential diagnosis of vertigo and dizziness in the emergency department. acta otolaryngol. 2014;134(2):140-5. 10. kerber ka, burke jf, brown dl, meurer wj, smith ma, lisabeth ld, et al. does intracerebral haemorrhage mimic benign dizziness presentations? a population based study. emerg med j. 2012;29(1):43-6. 11. moulin t, sablot d, vidry e, belahsen f, berger e, lemounaud p, et al. impact of emergency room neurologists on patient management and outcome. eur neurol. 2003;50(4):207-14. 12. savitz si, caplan lr, edlow ja. pitfalls in the diagnosis of cerebellar infarction. acad emerg med. 2007;14(1):63-8. 13. kerber ka, newman-toker de. misdiagnosing dizzy patients: common pitfalls in clinical practice. neurol clin. 2015;33(3):565-75. 14. newman-toker de, cannon lm, stofferahn me, rothman re, hsieh yh, zee ds. imprecision in patient reports of dizziness symptom quality: a cross-sectional study conducted in an acute care setting. mayo clin proc. 2007;82(11):1329-40. 15. bisdorff ar, staab jp, newman-toker de. overview of the international classification of vestibular disorders. neurol clin. 2015;33(3):541-50. 16. kattah jc. update on hints plus, with discussion of pitfalls and pearls. j neurol phys ther. 2019;43 (suppl 2):s42-s5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index m. saro-buendía et al. 6 17. newman-toker de, edlow ja. titrate: a novel, evidence-based approach to diagnosing acute dizziness and vertigo. neurol clin. 2015;33(3):577-99. 18. newman-toker de, kerber ka, hsieh yh, pula jh, omron r, saber tehrani as, et al. hints outperforms abcd2 to screen for stroke in acute continuous vertigo and dizziness. acad emerg med. 2013;20(10):986-96. 19. kattah jc, talkad av, wang dz, hsieh yh, newman-toker de. hints to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early mri diffusion-weighted imaging. stroke. 2009;40(11):3504-10. 20. kerber ka, morgenstern lb, meurer wj, mclaughlin t, hall pa, forman j, et al. nystagmus assessments documented by emergency physicians in acute dizziness presentations: a target for decision support? acad emerg med. 2011;18(6):619-26. 21. grewal k, austin pc, kapral mk, lu h, atzema cl. missed strokes using computed tomography imaging in patients with vertigo: population-based cohort study. stroke. 2015;46(1):108-13. 22. chalela ja, kidwell cs, nentwich lm, luby m, butman ja, demchuk am, et al. magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. lancet. 2007;369(9558):293-8. 23. savitz si, caplan lr. vertebrobasilar disease. n engl j med. 2005;352(25): 2618-26. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index introduction methods results discussion limitations conclusions declarations references archives of academic emergency medicine. 2023; 11(1); e7 ph oto qu i z an adult female with periumbilical pain and intractable vomiting; a photo quiz hamzah adel ramawad1∗, amirmohammad toloui2, adelaide viguri1 1. new york health and hospital coney island, brooklyn, new york. 2. physiology research center, iran university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 cite this article as: ramawad ha, toloui a, viguri a. an adult female with periumbilical pain and intractable vomiting; a photo quiz. arch acad emerg med. 2023; 11(1): e7. https://doi.org/10.22037/aaem.v11i1.1849. figure 1: the patient’s abdominopelvic computed tomography scan with oral and intravenous contrast. case presentation a 25-year-old female with no significant past medical history presented to the emergency room with complaints of worsening, sharp, periumbilical pain for two days, with an intensity of 8 out of 10 based on the visual analogue scale. she complained of fever, nausea, anorexia, and multiple episodes of non-bloody, non-bilious emesis. the patient appeared unwell and diaphoretic. her vital signs were as follows, blood pressure of 108/66 mmhg, heart rate of 106 beats/minute and body temperature of 39.3°c. physical examination showed a distended abdomen with localized tenderness and guarding in the periumbilical region. ∗corresponding author: hamzah adel ramawad; new york health and hospital coney island, brooklyn, new york, usa. email: hamzahr.adel@gmail.com, tel: +1(646)-725-2402, orcid: https://orcid.org/0000-0002-9687-3599. a point-of-care ultrasound (pocus) of the abdomen did not reveal any free fluid. laboratory testing, which included electrolytes, complete blood count, and renal and liver function revealed no significant abnormalities. pregnancy test was negative, and urinalysis was unremarkable. the findings of oral and intravenous contrast-enhanced computed tomography (ct) scan of the abdomen and pelvis are shown in figures 1a and 1b. what is your diagnosis? diagnosis oral and intravenous contrast-enhanced computed tomography (ct) scan of the abdomen and pelvis showed an enterolith within a tubular blind ending structure off the distal ileum with adjacent fat stranding (figures 2a and 2b). a diagnosis of meckel’s diverticulitis was made. meckel’s diverticulum is a rare congenital malformation of the gastrointestinal tract, which is difficult to diagnose in adults. this anomaly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index ha. ramawad et al. 2 figure 2: preoperative computed tomography (ct) images. coronal (a) and transverse (b) ct images with oral and intravenous contrast showed an enterolith (white arrow) in a tubular blind ending structure with the distal ileus with adjacent fat stranding. histopathology image of ectopic pancreatic cells and islets (black arrow) in meckel’s diverticulum (c). generally remains silent and asymptomatic; however, potential complications include perforation, hemorrhage, and bowel obstruction. most cases are incidentally discovered during radiographic imaging or during surgery performed for other reasons. this case presents the preoperative diagnosis of meckel’s diverticulum in an adult female who presented with symptoms of peritonitis. case course the patient was admitted for surgical management with intraoperative findings of a normal appendix and a perforated meckel’s diverticulum. the intestinal segment containing the diverticulum was resected with the creation of an endto-end anastomosis. the patient had a stable post-operative course on systemic antibiotics (cefazolin and metronidazole) without any complications and was discharged within a week. histopathology (figure 2c) later revealed a meckel’s diverticulum with suppurative diverticulitis containing ectopic pancreatic mucosa (1). discussion meckel’s diverticulum (md) is the most prevalent congenital malformation of the gastrointestinal tract, occurring in approximately 2% of the general population. it results from incomplete obliteration of the vitelline duct during the 7th or 8th weeks of gestation, leading to the formation of true diverticula (i.e., all layers of the gastrointestinal tract) in the small intestines (2). the diagnosis is usually made in childhood and has a 4% to 6% lifetime risk of developing complications with a male to female ratio of 3:1 (3). due to its rarity in adults and vast differential, preoperative diagnosis of md is uncommon. although meckel’s diverticulum generally remains silent, life-threatening complications such as gastrointestinal hemorrhaging, intussusception, bowel obstruction and formation of neoplasm or enterolith may arise (2). the risk of developing complications decreases with age and the incidence rate of developing a complication due to md is estimated to be less than 4% in the adult population, making it a very rare diagnosis (3). the rates of diverticulitis and perforation in patients with complicated md are approximately 12.7% and 7.3%, respectively according to the largest study done on md (4). these complications may present with nonspecific symptoms that mimic common intrabdominal pathologies like appendicitis or diverticulitis, making the diagnosis challenging in the adult population. heterotopic tissue is found in about 50% of all md cases, with gastric mucosa being the predominant type with a corresponding incidence of 60% to 85%. the presence of pancreatic mucosa is found in about 5% of all md cases. reports have also cited other tissues such as hepatic and endometrial, but these are quite rare and are not reported in complications (5). in this case, the md presented as peritonitis secondary to perforation and contained pancreatic tissue with enteroliths, making it an atypical presentation for an adult. when a patient with md presents to the emergency department, the symptoms are usually non-specific. patients often this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 3 archives of academic emergency medicine. yyyy; nn(i) present with abdominal tenderness, distension, and sometimes peritonitis. to overcome some of these difficulties, a ct scan with oral and intravenous contrast is recommended (6). when encountering a blind ending structure in the right lower quadrant apart from a normal appearing appendix, md should be considered as a differential diagnosis. the mortality of symptomatic md is approximately 6% and higher in elderly patients with comorbidities (7). patients with symptomatic md should be evaluated by a surgical team, especially if there is peritonitis, small bowel obstruction, or diverticulitis. treatment of symptomatic md is definitive diverticulectomy or bowel resection with anastomosis (2). this case emphasizes the importance of keeping md in the differential diagnosis, as making the diagnosis preoperatively allowed us to avoid complications of delayed surgical intervention. conclusion although most patients with meckel’s diverticulum remain asymptomatic, the diagnosis should be considered in patients with acute abdominal pain without other explanation. perforated md often presents with an acute abdomen and its preoperative diagnosis is difficult. to overcome some of these challenges, a ct scan with oral and intravenous contrast is recommended. treatment of symptomatic md is definitive surgery. declarations acknowledgments special thanks to mahmoud yousefifard, ph.d from (iran university of medical science, department of physiology) and jordan jeong, d.o (coney island hospital, department of emergency medicine) for their comments and feedback on the draft of this paper. ethical approval this case report received ethical approval from the new york city health and hospitals academic committee at coney island hospital (confirmation code: cih-22-16). we conducted this study in accordance with the helsinki declaration as revised in 2013. verbal and written consent for publication was obtained from the patient. sources of funding this work did not receive funding. conflict of interests all authors have declared that they have no conflict of interests. authors’ contribution study design: all authors data gathering: all authors data analysis: n/a interpreting the findings: all authors manuscript writing: all authors references 1. sagar j, kumar v, shah d. meckel’s diverticulum: a systematic review. journal of the royal society of medicine. 2006;99(10):501-5. 2. pedro f, romano j, rebelo m, matias r, carmo e. catastrophic gastrointestinal bleeding: always consider meckel’s diverticulum. european journal of case reports in internal medicine. 2019;6(12). 3. farah rh, avala p, khaiz d, bensardi f, elhattabi k, lefriyekh r, et al. spontaneous perforation of meckel’s diverticulum: a case report and review of literature. the pan african medical journal. 2015;20. 4. o’neill y, soler hm. atypical presentation of meckel’s diverticulum in a hispanic man: a case report. journal of surgical case reports. 2018;2018(4):rjy065. 5. madhyastha s, prabhu lv, saralaya v. meckel’s diverticulum: a case report. international journal of morphology. 2007;25(3):519-22. 6. bakshi vk, kaur m, bhatti g. “meckel’s diverticulum”–a diagnostic bizarre of abdominal pain in adults. adesh university journal of medical sciences & research. 2020;2(1):58-60. 7. tenreiro n, moreira h, silva s, madureira l, gaspar j, oliveira a. unusual presentation of a meckel’s diverticulum: a case report. international journal of surgery case reports. 2015;16:48-51. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index case presentation diagnosis discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 166 emergency (2014); 2 (4): 166-169 original research predictive factors of suicide attempt and non-suicidal self-harm in emergency department saad salman1*, jawaria idrees2, fahad hassan3, fariha idrees4, mashaal arifullah5, sareer badshah6 1. department of psychiatry and drug detoxification centre, post graduate medical institute, lady reading hospital, peshawar, pakistan 2. department of zoology, islamia college university, peshawar, pakistan 3. islamia college university, peshawar, pakistan 4. department of chemistry, islamia college university, peshawar, pakistan 5. jinnah college for women, peshawar, pakistan 6. department of statistics, islamia college university, peshawar, pakistan abstract introduction: suicide is the third cause of mortality in america, second leading cause of death in developed countries, and one of the major health problems. self-harm is self-inflicted damage to one’s self with or without suicidal intent. in the present study, the predictive factors of suicide attempt and non-suicidal self-harm were evaluated in patients referred to emergency department (ed) with these problem. methods: the total number of 45 patients with suicide attempt or self-harm admitted to ed were included. clinical symptoms, thoughts and behaviors of suicidal, and non-suicidal self-harm in these patients were evaluated at baseline. suicidality, suicidal intent and ideation, non-suicidal self-injury, social withdrawal, disruptive behavior, and poor family functions were evaluated at admission time. brief clinical visits were scheduled for the twelfth weeks. in the twelfth week, patients returned for their final visit to determine their maintenance treatment. finally, data were analyzed using chi-squared and multiple logistic regression. results: forty-five patients were included in the study (56.1% female). the mean age of patients was 23.3±10.2 years (range: 15-75; 33.3% married). significant association of suicide and self-injury was presented at the baseline and in the month before attempting (p=0.001). the most important predictive factors of suicide and self-harm based on univariate analysis were depression (suicidal and non-suicidal items of hamilton depression rating scale), anxiety, hopelessness, younger age, history of nonsuicidal self-harm and female gender (p<0.05). the participants’ quality of life analysis showed a significant higher quality in physical component summary (p=0.002), mental component summary (p=0.001), and general health (p=0.001) at follow up period. conclusion: at the time of admission in ed, suicide attempt and non-suicidal selfharm are subsequent clinical markers for the patient attempting suicide again. the most independent predictive factors of suicide attempt and self-harm were poor family function, hopelessness, non-suicidality items of hamilton depression rating scale, history of non-suicidal self-harm, and anxiety disorders. key words: suicide, attempted; self-injurious behavior; emergency services, psychiatric; mental disorders; predictive value cite this article as: salman s, idrees j, hassan f, idrees f, arifullah m, badshah s. predictive factors of suicide attempt and nonsuicidal self-harm in emergency department. emergency. 2014;2(4):166-9. introduction:1 uicide is the third cause of mortality in america, second leading cause of death in developed countries, and one of the major health problems globally (1-4). suicidality in adults have been remarkably recognized as a factorial analysis of family perceptions, childhood abuse, social integration or neglect, and other social factors that can be a reason for the suicide attempt (5, 6). anxiety disorders and depression increase *corresponding author: saad salman; department of psychiatry and drug detoxification centre, post graduate medical institute, lady reading hospital, pakistan. fax/tel: 091-9222009; email: saadirph@gmail.com received: may 2014; accepted: july 2014 the jeopardy for suicide and suicidal intent, ideation and behavior. it maybe increases the risk even more, if the depression, anxiety, and hopelessness left untreated (7, 8). the relationship between suicide attempts and other psychiatric disorders such as eating, anxiety, conduct, and substance use disorders is very common. non-suicidal self-harm (nssh) is “self-inflicted damage to one’s self that lack evidence of suicidal intent” (9). on the other hand, self-harm can be defined as “attempt of harming one’s self with or without suicidal intent” (10, 11). based on above-mentioned, the aim of the present study was to evaluate predictive factors of suicide attempt and non-suicidal self-harm in patients referring s mailto:saadirph@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 167 salman et al to emergency department (ed). methods: this prospective cohort study was conducted in ed of lady educational hospital, post graduate medical institute peshawar, pakistan, during may to october 2012. the study protocol was approved by local ethic committee and in accordance with helsinki declaration. all respondents completed informed consent. the subjects were followed twelfth weeks after admission. forty-five patients with suicidal attempt or self-harm, referred to the study protocol by their primary care provider immediately at the time of admission, were consequently entered to the study. the exclusion criteria were as follow: subjects who were received antidepressant-antipsychotic (alone or in combination during the preceding six months), co-morbid mania or bipolar disorder, psychotic symptoms, and substance use disorder or dependence. suicidality, suicidal intent and ideation, non-suicidal self-injury during the before month, social withdrawal, disruptive behavior, family functions, and quality of life were evaluated and submitted in data gathering files at the time of admission. mcmaster family assessment device 12-item was used to check the patient’s family and social condition (12). hamilton depression rating scale was applied to assess the depression in the participants (13). for checking the physical health of patients, general functioning scale was used (14). a clinical visit was scheduled for the twelfth weeks to regular psychiatric follow-ups. the clinical progress were evaluated during face-to-face encounter. in this context, suicide/self-harm attempt and quality of life (the sf-36 questionnaire) (15) during follow ups period were asked from subjects. patients were divided to two groups included suicide or self-harm and those who lack of them during the follow up period. demographic variables and other baseline values were compared between both groups. the t-test was performed for continuous data and chi-squared analysis conducted for categorical or dichotomous data. potential differences were reported in terms of statistical significance (p-value) as well as odds ratio (or) whenever applicable. statistical significant differences were defined as a p-value less than 0.05. spss version 20.0 was used for data analysis. results: forty-five patients were included in the study (56.1% female). the mean and standard deviation of patients’ age was 23.3±10.2 years (range: 15-75, 33.3% married). table 1 summarizes the baseline demographics data of patients. eight (17%) cases attempted suicide in the before month and 15 (33%) ones during the followup period. significant association of suicide and selfharm was presented at the baseline and in the month before attempting (p=0.001). in addition, there was a remarkable relationship between suicidal intent and attempt at the time of admission and the last month (p=0.01). social problems was significantly associated with self-harm which consequently prop up the patient to attempt suicide (odds ratio=1.8, p=0.055). the most important predictive factors of suicide and self-harm based on univariate analysis were depression (suicidal and non-suicidal items of hamilton depression rating scale), anxiety, hopelessness, younger age, history of non-suicidal self-harm and female gender (p<0.05). table 2 and 3 show the results of multivariate logistic regression analysis of independent predictive factors of suicide and self-harm, respectively. as it can be seen only family function (p=0.0001), hopelessness (p= 0.02) and higher levels of non-suicidality items of hamilton scale (p=0.03) were independent predictors of suicidal attempt in follow up period. as well, independent predictors of self-harms in fallow up period were history of non-suicidal self-harm (p<0.003), higher levels of nonsuicidality items of hamilton scale (p=0.023), hopelessness (p= 0.001), and anxiety (p=0.011). table 4 shows the quality of life at baseline and follow up. the participants’ quality of life analysis showed a significant higher quality in physical component summary (p=0.002), mental component summary (p=0.001), and general health parameters (p=0.001) at follow up period. discussion: the present study was based on evaluating the reasons of suicide attempt and non-suicidal self-harm. based on the main findings of the present study the most important predictive factors of suicide attempt and selfharm were as follow: family function, hopelessness, and non-suicidality items of hamilton scale, history of nonsuicidal self-harm, and anxiety. this investigation revealed that hopelessness plays an important role in table 1: baseline demographic characteristics of participants. demographic parameters number (%) age (years) 23.3 (sd=10.2) gender female 25 (56.1) male 20 (43.9) marital status married 15 (33.3) single 30 (66.7) educational level graduate 10 (22.7) under graduate 15 (33.0) under diploma 20 (44.3) occupational status employed 6 (13.3) unemployed 39 (86.7) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (4): 166-169 168 future suicides. another important finding of this study was that depression did not clearly indicate if theywould commit suicide again or not. hopelessness and self-harm were two independent variables. the quality of life of the patient was lower at baseline. furthermore, it indicated that the patient’s mental and physical conditions encouraged the subject to attempt suicide or at least injure, because of catch the attention or due to hopelessness. quality of life scores were lower but for hopelessness greater at baseline. self-harm was highly reflected the abysm of social mishaps and a greater level of complexity among the young adolescents as well as adults (1, 9, 10). hopelessness and anxiety disorders were correlated with self-injury but it was not apparent that the patient attempted suicide as well (16). one study revealed that depressed patients, who were hospitalized, were not prone to suicide. but the ratio of self-harm among the depressed adolescents was more than the healthy young participants (17, 18). the potential risks of suicide at baseline and follow-up caused the patient to attempt subsequent suicide. the reason of the attempt(s) were severity of depression, anxiety, hopelessness, loss of a friend, unwanted sex, unwilling separation from a friend or partner, drug abuse, rape, parental problems, and problems with siblings (3, 18). non-suicidal self-injury is a common practice among adolescents, thus the results cannot be only generalized to this fact that one or more attempt may not lead to the suicide. for further validation of the results, they should be checked on a larger population. limitation during the course of study, several variables left “untreated” including data collection for substance abuse, drug or alcohol addiction as well as prescriptive drug addiction, personality disorders, suicidal intent in the previous life history, and previous mental illnesses that table 2: independent predictors of suicide attempt based on multivariate logistic regression analysis. variable odds ratio 95% confidence interval p suicidality item of hamilton scale 3.20 0.82–5.25 0.51 history of non-suicidal self-harm 3.43 0.20–8.43 0.23 non-suicidality items of hamilton scale 2.53 1.55–2.90 0.03 hopelessness 2.44 1.29–3.80 0.02 family functioning 4.11 1.53–5.19 <0.001 age 0.50 0.38–1.13 0.32 female 1.34 0.34–1.66 0.41 table 3: independent predictors of suicidal self-harm during follow-up based on multivariate logistic regression analysis  variable odds ratio 95% confidence interval p suicidality items of hamilton scale 0.60 0.55–1.49 0.55 history of non-suicidal self-harm 23.2 5.87–60.1 0.003 non-suicidality items of hamilton scale 1.80 1.37–2.23 0.02 hopelessness 2.94 1.49–8.71 0.001 family functioning 1.15 0.42–1.68 0.34 anxiety disorder 3.77 1.38–10.65 0.01 table 4: quality of life scores of the patients at baseline and follow up period of the study  items baseline mean (sd) follow up mean (sd) p mental component summary 41.3 (8.60) 68.3 (9.10) 0.001 physical functioning 38.1 (35.9) 39.0 (28.5) 0.56 vitality 57.3 (23.9) 56.2 (21.2) 0.87 physical role 51.2 (25.1) 51.0 (19.3) >0.99 body pains 47.9 (26.9) 64.5 (13.3) 0.003 physical component summary 34.4 (4.10) 46.7 (5.70) 0.002 general health 38.8 (29.9) 54.8 (25.5) 0.001 social functioning 53.2 (21.7) 69.8 (18.0) 0.77 emotional role 57.0 (23.2) 52.4 (21.8) 0.86 mental health 65.6 (17.0) 78.3 (10.8) 0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 169 salman et al lead to self-harm and suicide. conclusion: at the time of admission in ed, suicide attempt and non-suicidal self-harm are subsequent clinical markers for the patient attempting suicide again. the most independent predictive factors of suicide attempt and selfharm were family function, hopelessness, nonsuicidality items of hamilton depression rating scale, history of non-suicidal self-harm, and anxiety disorders. acknowledgments: the following individuals are acknowledged for their support, encouragement and guidance. dr. samiullah, dr. gohar ali, dr. ismail, ma’am naila riaz awan and ma’am sehrish. psychologists (interns): mehreen, sumreen, faiza for their help. conflict of interest: none funding support: none authors’ contributions: the first two authors helped in idea inception, designing of the study and data interpretation. third, fourth and fifth author participated in drafting the article and revised it critically, helped in data collection, analysis of the data and gave final approval of the version to be submitted. sixth author helped in statistical analysis, acquisition and interpretation of data. 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psychiatr scand. 2006;113(3):180206. 18. mork e, walby fa, harkavy-friedman jm, et al. clinical characteristics in schizophrenia patients with or without suicide attempts and non-suicidal self-harm-a cross-sectional study. bmc psychiatry. 2013;13(1):1-8. emergency. 2017; 5 (1): e41 br i e f re p o rt brain ultrasonography findings in neonatal seizure; a cross-sectional study seyed saeed nabavi1∗. parinaz partovi1 1. clinical research development center, amir-almomenin hospital, islamic azad university, tehran medical sciences branch, tehran, iran. received: december 2016; accepted: december 2016; published online: 12 january 2017 abstract: introduction: screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. the present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. methods: the present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 28 day old newborns. results: 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. a correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). conclusion: based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. hemorrhage (12%) and hydrocephaly (7%) were the most common findings. the only factor correlating with increased probability of positive findings was the newborns being pre-term. keywords: seizures; infant, newborn; ultrasonography; diagnosis; brain © copyright (2017) shahid beheshti university of medical sciences cite this article as: nabavi s, partovi p. brain ultrasonography findings in neonatal seizure; a cross-sectional study. emergency. 2017; 5(1): e41. 1. introduction s eizure is the most common neurologic problem in infants, recurrence of which can cause disturbance in the central nervous system growth process. most cases of seizure are idiopathic; but neonatal seizure is usually a sign of a pathologic problem in the brain that may be accompanied by a permanent damage in future stages of life (1, 2). prevalence of newborn seizure is reported to be between 1.8 and 8.6 in each 1000 live births (2). the considerable difference in the reported statistics can be related to problem in diagnosis, different definitions of neonatal seizure, and various populations. sometimes determining which clinical phenomenon should be considered to be seizure is a difficult task (3). the most common causes of neonatal seizure are hypoxiaischemia (asphyxia), brain stroke, intra-ventricular or intracranial hemorrhage, meningitis, sepsis, and metabolic ∗corresponding author: seyed saeed nabavi; department of pediatrics; amir-almomenin hospital, shirmohammadi street, naziabad, tehran, iran. email: seyedsaeednabavi@yahoo.com tel: 00989122405399 disorders (4, 5). recent studies have shown that the nervous system of newborns may be resistant to long-lasting seizures to some extent; however, recurrent short seizures may be associated with permanent damage to the central nervous system, increased risk of epilepsy and durable cognitive disabilities (1, 6). screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. electroencephalogram (eeg) has been reported to be abnormal in 100% of clonic, partial tonic, and spasmic seizures; 60% of generalized myoclonic ones; 7% of focal and multifocal myoclonic, and 10% of generalized tonic seizures. meanwhile, silent, apnostic, and autonomic types of seizure do not have a known correlation with eeg findings (7). brain magnetic resonance imaging (mri), computed tomography (ct) scan, and eeg, despite having a high accuracy are not available everywhere and require special conditions such as immobilization. currently, ultrasonography is considered to be used for various purposes such as measuring intracranial pressure (8, 9), fracture diagnosis (10-12), etc. in emergency setting (13, 14). although the ability of ultrasonography in detection of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. nabavi et al. 2 newborn intracranial lesions has been introduced during the 1990s, it has not been seriously considered until now, especially in third world countries (15). it seems that ultrasonography as a safe, affordable, available and bedside screening tool can be of great help for physicians in charge of such patients (16-19). therefore, the present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. 2. methods 2.1. study design and setting the present study is a retrospective cross-sectional one aiming to evaluate brain ultrasonography findings of newborns hospitalized in the neonatal unit of milad hospital, tehran, iran, during 2011 to 2013 complaining seizure. researchers adhered to principles of helsinki declaration and confidentiality of patient data. this study was approved by the ethics committee of islamic azad university, tehran medical sciences branch. 2.2. participants newborns hospitalized in neonatal unit following seizure were studied using convenience sampling. age between 1 and 28 days; presence of tonic, clonic, myoclonic, and autonomic; no missing data in the clinical profile of the newborn; availability of data on brain ultrasonography of the newborn, and not having history of trauma were among the inclusion criteria. newborns with a history of apnea due to pulmonary, cardiac, digestive, and infectious problems as well as those who did not have a definite diagnosis of seizure were excluded from the study. 2.3. data gathering using the clinical profile of the patients, a checklist consisting of demographic data including age, sex, birth weight, birth age, family history of neonatal seizure, history of underlying illnesses, and type of birth as well as brain ultrasonography findings was filled for each of them. neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks based on mizrahi and kellawaycriteria in 1 – 28 day old patients (20). data gathering was done by a trained medicine student. ultrasonography was done using a 3.5 – 5 mhz curve probe. all ultrasonography examinations were performed from the anterior fontanelle, by a single radiologist. 2.4. statistical analysis data analysis was done using spss version 13. quantitative data were reported as mean and standard deviation (sd) and qualitative ones as frequency and percentage. for evaluating the correlation between ultrasonography findings and detable 1: baseline characteristics of the studied newborns variable number (%) age (days) 0 – 9.9 78 (76) 10 – 19.9 13 (13) 20 – 28 9 (9) birth weight (gr) low (< 2500) 16 (16) normal (2500 – 4000) 81 (81) high (> 4000) 3 (3) delivery type natural 33 (33) cesarean section 67 (67) birth age term 83 (83) pre-term 17 (17) family history of seizure yes 6 (6) no 94 (94) underlying problem yes 27 (27) no 73 (73) variable number (%) normal 78 (78) hemorrhage 12 (12) hydrocephaly 7 (7) other 3 (3) table 2: brain ultrasonography findings of the newborns with seizure variable number (%) normal 78 (78) hemorrhage 12 (12) hydrocephaly 7 (7) other 3 (3) mographic data of the patients, chi-square and anova tests were used. p< 0.05 was considered as significance level. 3. results 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). table 1 depicts the baseline characteristics of the studies patients. most newborns were in the < 10 days age range (78%), term (83%) and with normal birth weight (81%). 6 (6%) newborns had a history of seizure and 27 (27%) cases had an underlying illness. table 2 shows the brain ultrasonography findings of the studied newborns. 22 (22%) of the ultrasonography examinations showed a pathologic finding. table 3 demonstrates the correlation between ultrasonography findings and demographic data of the patients. a correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e41 table 3: the correlation between ultrasonography findings and baseline characteristics of the newborns with seizure variable pathologic findings n (%) p value yes no sex male 14 (24.1) 44 (75.9) 0.544 female 8 (19) 34 (81) birth weight (gr) low (< 2500) 5 (31.2) 11 (68.8) normal (2500 – 4000) 16 (19.8) 65 (80.2) 0.343 high (> 4000) 1 (23.3) 2 (67.7) delivery type natural 7 (21.2) 26 (78.8) 0.894 cesarean section 15 (22.4) 52 (77.6) birth age term 22 (10.1) 68 (81.9) 0.023 pre-term 7 (41.2) 10 (58.8) higher in pre-term newborns (p = 0.023). 4. discussion based on the findings of the present study, 22% of the hospitalized newborns in the neonatal unit of the studied hospital had at least 1 pathologic finding in their brain ultrasonography. hemorrhage and hydrocephaly with 12 and 7 cases were the most common ultrasonography findings, respectively. the only factor correlating with increased probability of positive findings in brain ultrasonography was the newborns being pre-term. in a study by zahid et al. carried out in 2010 and 2011 for evaluation of brain ultrasonography findings in newborns with seizure, 48.5% of the performed ultrasonography examinations had pathologic findings such as: intraventricular hemorrhage (27.6%), brain edema (11.7%), subdural hemorrhage (6.4%), and subarchanoid hemorrhage (5.3%). they introduced ultrasonography as a proper non-invasive method for timely diagnosis of cerebral causes of seizure in newborns (19). in our study, although the number of ultrasonography examinations with positive finding was half the rate reported in the mentioned study, 22% prevalence of ultrasonography findings was also important. in leth et al. study, based on brain ultrasonography findings, the cause of 10% of newborn seizures was determined to be brain lesions, while this rate rose to 68% after performing mri. in the study, 35% of the seizures were reported to be due to hypoxic problems, 26% hemorrhagic, 16% metabolic disorders and unknown in 23% (16). in a study by mercuri et al. 11 out of 16 newborns with seizure (69%) had pathologic lesions in their brain ultrasonography, which were mostly hemorrhagic in the initial weeks and ischemic after that (17). this rate was estimated to be 95% in rutherford et al. study. small infarcts that had not been detected in ultrasonography were seen in mri (18). wang et al. in their study in 2004 concluded that ultrasonographic screening of brain for all newborns can be helpful in detection of rare but important problems affecting neurologic outcomes (21). considering the vastly different results that exist regarding the rate of pathologic findings detected by brain ultrasonography, it seems that further studies with larger sample sizes and more accurate methodologies are required before making a final decision in this regard. in addition, to determine the screening performance characteristics of this test, it should be compared to more standard diagnostic tests such as mri and determine its sensitivity, specificity, and accuracy. 5. conclusion: based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. hemorrhage (12%) and hydrocephaly (7%) were the most common findings. the only factor correlating with increased probability of positive findings was the newborns being pre-term. 6. appendix 6.1. acknowledgements authors would like to thank all the staff of pediatric department of milad hospital, tehran, iran. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding/support none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. nabavi et al. 4 6.4. conflict of interest none. references 1. volpe jj. neurology of the newborn: elsevier health sciences; 2008. 2. fanaroff aam, fanaroff rjaa, martin rj, klaus mhf, avroy a. neonatal-perinatal medicine: diseases of the fetus and infant: mosby; 2002. 3. saliba r, annegers j, mizrahi e. incidence of clinical neonatal seizures. epilepsia. 1996;37(5ŝsuppl). 4. temko a, thomas e, marnane w, lightbody g, boylan g. eeg-based neonatal seizure detection with support vector machines. clinical neurophysiology. 2011;122(3):464-73. 5. sood a, grover n, sharma r. biochemical abnormalities in neonatal seizures. the indian journal of pediatrics. 2003;70(3):221-4. 6. yäśldäśz ep, tatläś b, ekici b, eraslan e, aydäśnläś n, ãğaläśå§kan m, et al. evaluation of etiologic and prognostic factors in neonatal convulsions. pediatric neurology. 2012;47(3):186-92. 7. zupanc ml. neonatal seizures. pediatric clinics of north america. 2004;51(4):961-78. 8. amini a, eghtesadi r, feizi am, mansouri b, kariman h, arhami dolatabadi a, et al. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. 2013. 2013;1(1):5. 9. amini a, kariman h, dolatabadi aa, hatamabadi hr, derakhshanfar h, mansouri b, et al. use of the sonographic diameter of optic nerve sheath to estimate intracranial pressure. the american journal of emergency medicine. 2013;31(1):236-9. 10. shojaee m, hakimzadeh f, mohammadi p, sabzghabaei a, manouchehrifar m, arhami dolatabadi a. screening characteristics of ultrasonography in detection of ankle fractures. 2016. 2016;4(4):4. 11. bozorgi f, shayesteh azar m, montazer sh, chabra a, heidari sf, khalilian a. ability of ultrasonography in detection of different extremity bone fractures; a case series study. 2016. 2016;4. 12. yousefifard m, baikpour m, ghelichkhani p, asady h, darafarin a, amini esfahani mr, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. 2016. 2016;4(2):10. 13. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, haji ghanbari mj, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. 2015. 2015;3(4):10. 14. golshani k, esmailian m, valikhany a, zamani m. bedside ultrasonography versus brain natriuretic peptide in detecting cardiogenic causes of acute dyspnea. 2016. 2016;4(3):5. 15. volpe jj, editor brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. seminars in pediatric neurology; 1998: elsevier. 16. leth h, toft p, herning m, peitersen b, lou h. neonatal seizures associated with cerebral lesions shown by magnetic resonance imaging. archives of disease in childhood-fetal and neonatal edition. 1997;77(2):f105f10. 17. mercuri e, cowan f, rutherford m, acolet d, pennock j, dubowitz l. ischaemic and haemorrhagic brain lesions in newborns with seizures and normal apgar scores. archives of disease in childhood-fetal and neonatal edition. 1995;73(2):f67-f74. 18. rutherford ma, pennock jm, dubowitz l. cranial ultrasound and magnetic resonance imaging in hypoxicâăřischaemic encephalopathy: a comparison with outcome. developmental medicine & child neurology. 1994;36(9):813-25. 19. zahid h, farid a. cranial ultrasonography findings and immediate outcome of neonates with seizure. ds (child) h j 2011;27(2):72-8. 20. mizrahi em, kellaway p. characterization and classification of neonatal seizures. neurology. 1987;37(12):1837-. 21. wang lw, huang cc, yeh tf. major brain lesions detected on sonographic screening of apparently normal term neonates. neuroradiology. 2004;46(5):368-73. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion: appendix references archives of academic emergency medicine. 2023; 11(1): e37 ph oto qu i z an 85-year-old man with gradual decrease in the level of consciousness and vomiting; a photo quiz talayeh mirkarimi1∗, mohammad salek1 1. emergency department, alborz university of medical science, karaj, iran. 2. haematology, oncology and stem cell transplantation research center, shariati hospital, tehran university of medical sciences, tehran, iran. received: march 2023; accepted: april 2023; published online: 7 may 2023 cite this article as: mirkarimi t, salek m. an 85-year-old man with gradual decrease in the level of consciousness and vomiting; a photo quiz. arch acad emerg med. 2023; 11(1): e37. https://doi.org/10.22037/aaem.v11i1.2030. figure 1: brain computed tomography (ct) scan of the patient without contrast materials. 1. case presentation an 85-year-old male was brought to emergency department (ed) from a nursing facility with gradual onset of lethargy and vomiting from a week ago. no clear history of head trauma and coagulopathy or using of anticoagulant agents. his past medical history included mild cognitive impairment (mci) and diabetes mellitus, which were treated using ∗corresponding author: talayeh mirkarimi; alborz university of medical sciences, taleghani blvd, taleghani square, karaj, iran. email: t_mirkarimi@yahoo.com, orcid: https://orcid.org/0000-0002-3644-3925. oral agents. on general examination, the patient looked underweight with body mass index (bmi) about 17. neither specific stationary position of the limbs nor any spontaneous motor behavior were detected. the patient’s vital signs on admission to ed were: blood pressure: 140/60 mmhg, pulse rate: 82 beats/minute, oxygen saturation: 95%, respiratory rate: 16/minute, and bedside blood-glucose measurement: 268 mg/dl. the patient was afebrile. on neurologic examination in ed, glasgow coma scale (gcs) was 10/15 (eye: 3, motor: 5, verbal: 2). mucosal membranes were dry and patient seemed to be dehydrated. pupils were equal but had poor reaction to light. oculocephalic maneuver, corneal reflex, and gag reflex were intact. there was slight decrease this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. mirkarimi & m. salek 2 in muscle tones in lower limbs. plantar reflex on both sides seemed upright. arm and leg dropping test showed equal motor response and deep tendon reflexes (dtr) seemed diminished on both sides. laboratory tests included: leukocyte count: 12800/mm3 with 85% segmented neutrophils, hemoglobin: 14.1 g/dl, platelet: 268000/microliter, glucose: 234 mg/dl, sodium: 141 meq/l, potassium: 5.1 meq/l, blood urea nitrogen (bun): 36 mg/dl, serum creatinine: 1.3 mg/dl, and international normalized ratio (inr) was 1.24. the patient underwent brain computed tomography (ct) scan without contrast materials, which is shown in figure 1. what is your diagnosis? 1.1. diagnosis bilateral subdural hematoma with bilateral hematocrit effect (figure1) without any midline shift or patency in basal cisterns. 1.2. case fate the patient underwent bilateral burr-hole insertion, which is shown in figure 2. clinical and neurological conditions did not improve after surgery. unfortunately, the patient died 10 days after surgery due to intubation complications. 2. discussion chronic subdural hematoma (csdh) is common in older adults, particularly after mild head trauma. this condition is caused by the accumulation of blood or blood derivatives in the subdural space and is usually known as a benign disease (1). the prevalence of csdh is increasing throughout the world due to the ageing population. the peak age of csdhs onset has also increased and is regarded as a serious public health problem (2). csdh symptoms vary from asymptomatic to a clear loss of consciousness and usually become symptomatic more than two weeks after the initial trauma. csdh symptoms include cognitive deficits, impaired memory, personality changes, and focal neurological signs. since csdh can imitate many neurological conditions, it is referred to as the great neurologic imitator (3). many factors are currently considered effective in csdh in elderly patients, including, older age, alcohol usage, diabetes mellitus (dm), coagulopathy, antiplatelet and anticoagulant agents, and arachnoid cyst also rarely reported after epidural anesthesia (4). dehydration and diuretic usage is another risk factor that implicates the occurrence and recurrence of csdh (5). obesity, which is a risk factor of csdh, is also associated with decreased mortality rate after surgical evacuation of the hematoma (6). bilateral csdh is far less common than unilateral csdh, and its clinical and radiological characteristics are scarcely known. bilateral csdh progresses faster and has a higher risk of cerebral herniation, resulting in worse outcomes than unilateral csdh. patients with bilateral sdh are less likely to suffer hemiparesis than patients with unilateral sdh. moreover, the recurrence of sdh is more likely in bilateral cases. patients with bilateral sdh are older than those with unilateral type, and the prevalence of alcohol use is lower in these patients. the bilateral type is commonly manifested with nausea and vomiting, and midline shift is less likely in these patients. it is most frequently seen in the setting of anticoagulation therapy or coagulopathy (7). hematocrit effect also called blood-fluid level and hemorrhagic sedimentation is a rare condition and is caused by rebleeding in csdh. it is the result of the separation of heavier cellular elements of blood located lower to a lighter liquid supernatant which could be seen on ct or magnetic resonance imaging (mri) (8). the treatments of sdh include burr hole craniotomy (bhc) (9), the use of corticosteroids as monotherapy or combined with surgery, which decreases the risk of recurrence of csdh and watchful waiting (10). surgery is carried out in symptomatic cases, size more than 10 mm, or midline shifts more than 5 mm. watchful waiting is exercised in patients with small, asymptomatic sdh, with no symptoms indicating increasing intracranial pressure (2). the prognosis is significantly worse in patients over 75 years old compared to those younger than 75 years (7). 3. conclusion we should consider the csdh as an important and probably treatable cause of decrease in the level of consciousness in old age, especially in patients with known risk factors. 4. declarations 4.1. acknowledgments we thank dr. mehran moradi, neurosurgeon who participated in case management. 4.2. conflict of interest tm and ms declare that they have no conflict of interest. 4.3. fundings and supports tm and ms received no financial support for authorship or publication of this article. 4.4. authors’ contribution tm and ms both contributed to writing of this manuscript and meet the criteria of authorship. 4.5. ethical consideration and patient consent written informed consent was obtained from patient’s son for publication of this case report and accompanying image. the proposal has been approved by the research ethics this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e37 figure 2: post-surgery spiral brain computed tomography scan without contrast after burr hole insertion; revealing appropriate evacuation of subdural hematoma in both sides. committees of alborz university of medical sciences. references 1. yang w, huang j. chronic subdural hematoma: epidemiology and natural history. neurosurg. clin. n. am. 2017;28(2):205-10. 2. uno m, toi h, hirai s. chronic subdural hematoma in elderly patients: is this disease benign? neurol. med. chir (tokyo). 2017;57(8):402-9. 3. yadav y, parihar v, namdev h, bajaj j. chronic subdural hematoma. asian j. neurosurg. 2016;11(04):330-42. 4. kostić a, kehayov i, stojanović n, nikolov v, kitov b, milošević p, et al. spontaneous chronic subdural hematoma in elderly people–arterial hypertension and other risk factors. j chin med assoc. 2018;81(9):781-6. 5. mainka n, borger v, hadjiathanasiou a, hamed m, potthoff a-l, vatter h, et al. dehydration status at admission predicts recurrence in patients with traumatic chronic subdural hematoma j. clin. med.. 2022;11(5):1178. 6. hallan dr, freedman z, rizk e. obesity paradox and surgical evacuation for chronic subdural hematoma. cureus. 2022;14(4):e24002. 7. lee j, park jh. clinical characteristics of bilateral versus unilateral chronic subdural hematoma korean j . neurotrauma. 2014;10(2):49. 8. tan s, aronowitz p. hematocrit effect in bilateral subdural hematomas. j. gen. intern. med. 2013;28(2):321-. 9. májovský m, netuka d, beneš v, kučera p. burr-hole evacuation of chronic subdural hematoma: biophysically and evidence-based technique improvement. j neurosci rural pract. 2019;10(01):113-8. 10. shi m, xiao l-f, zhang t-b, tang q-w, zhao w-y. adjuvant corticosteroids with surgery for chronic subdural hematoma: a systematic review and meta-analysis. front neurosci. 2021;8(15):786513. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index case presentation discussion conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e20 or i g i n a l re s e a rc h pattern of neurological disorders among patients evaluated in the emergency department; cross–sectional study mohamed sheikh hassan1∗, nor osman sidow1, alper gökgül1, bakar ali adam1, mohamed farah osman1, hussein hassan mohamed2, ismail gedi ibrahim3, ishak ahmed abdi4 1. department of neurology, mogadishu somali turkish training and research hospital, mogadishu, somalia. 2. department of emergency medicine, mogadishu somali turkish training and research hospital, mogadishu, somalia. 3. department of radiology, mogadishu somali turkish training and research hospital, mogadishu, somalia. 4. department of cardiology, mogadishu somali turkish training and research hospital, mogadishu, somalia. received: october 2022; accepted: december 2022; published online: 21 january 2023 abstract: introduction: neurologic disorders are common reasons for emergency consultations. most neurologic disorders seen in the emergency department (ed) are life-threatening and require urgent treatment. the goal of this study is to investigate the pattern of neurological disorders among patients evaluated in the ed. methods: this is a cross-sectional study conducted in the ed of mogadishu somali turkish training and research hospital, from july 2021 to february 2022. the clinical and epidemiological characteristics of adult patients with neurologic manifestations in the ed were evaluated. age, gender, distribution of neurological disease manifestations, neurological examination findings, and neurological diagnoses made by consultant neurologists were assessed. results: during the study period, 321 patients were assessed (3.7% of all ed admissions). the majority of the patients in the study were above 50 years of age (62.6% male). hypertension was the most common comorbidity among these patients with 122 (38%) cases, followed by diabetes mellitus with 65 (20.2%), and heart diseases with 26 (8.1%) cases. the main reasons for neurology consultations were altered mental status with 141 (44%) cases, motor weakness with 102 (31.8%), seizures with 33 (10%), headache with 17 (5.3%), and vertigo with 9 (2.8%) cases. 196 (61%) had hemiplegia, 60 (18.7%) had consciousness impairment, and 38 (11.8%) had normal neurological examination. the most frequent neurological diagnoses were ischemic strokes with 125 (39%) cases, hemorrhagic strokes with 65 (20.2%), epileptic seizures with 28 (8.7%), and metabolic encephalopathies with 13 (4%) cases. the median duration of the neurology consultations was 20 minutes. 251 (78%) of the patients were admitted to the hospital, while 70 (22%) were discharged from the emergency department. after neurology consultation, the neurology department made the most admissions with 226 (90%) cases, while 25 (10%) were admitted by other departments. of those admitted, 186 (74.2%) were admitted to the neurology ward, and 65 (25.8%) were admitted to the intensive care unit. conclusion: in our study, neurologic emergencies accounted for 3.7% of all emergency admissions. stroke, epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases were the most common neurological disorders. the admission rate was very high following neurologic assessment by neurologists. keywords: nervous system diseases; stroke; emergency service, hospital; comorbidity; somalia cite this article as: sheikh hassan m, osman sidow n, gökgül a, ali adam b, farah osman m, hassan mohamed h, gedi ibrahim i, ahmed abdi i. pattern of neurological disorders among patients evaluated in the emergency department; cross–sectional study. arch acad emerg med. 2023; 11(1): e20. https://doi.org/10.22037/aaem.v11i1.1813. ∗corresponding author: mohamed sheikh hassan; department of neurology, mogadishu somali turkish training and research hospital, mogadishu, somalia. tel: +252615609080, email:dr.m.qalaf@gmail.com, orcid: https://orcid.org/000-0001-7236-1524. 1. introduction neurological disorders comprise 9% of total emergency department (ed) admissions (1). the majority of neurological emergencies are life-threatening conditions that necessitate immediate diagnosis and treatment. if not recognized and treated early, they can have catastrophic effects, resulting in long-term impairment or death (2). patients presenting to eds with neurological diseases should be examined as soon this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. sheikh hassan et al. 2 as possible and managed in a multidisciplinary manner, as some of these disorders are associated with other medical and non-medical conditions (3). as demonstrated by a study in the united kingdom, 10% of ed admissions have at least one neurological complaint, 10%–20% of acute hospitalizations are for neurological disorders, and 8–15% of all patients admitted to the ed require a neurologist’s evaluation (4). cerebrovascular diseases, epileptic seizures, central nervous system (cns) infections, encephalopathies, and myelopathies are the commonest neurological disorders admitted to the ed (5). in one study in ethiopia, neurological emergencies accounted for 5.27% of the total medical emergencies. hemiparesis, altered mental status, and seizures were the most common neurological presentations, accounting for 44%, 19.3%, and 13.1% of all cases, respectively. cerebrovascular disorders (54%), hiv/aids related neurologic sequels (9%), meningitis (8.7%), and seizures (7%) were the most common neurologic disorders diagnosed (6). somalia is a developing country with limited medical resources. the provision of high-standard healthcare is limited by a lack of human resources, mainly trained health professionals for the management of diseases. due to the lack of sufficient neurologists in the country, the majority of neurological disease manifestations in eds are evaluated by nonneurologists, mainly by general practitioners. there is no previous data on the epidemiological profile of patients with neurological emergencies in the ed in somalia. our objective is to evaluate the demographic characteristics, clinical profile, and neurologic disease pattern among patients evaluated in the ed of a tertiary care hospital in mogadishu, somalia. 2. methods 2.1. study design and settings this is a cross-sectional study conducted in the ed of mogadishu somali turkish training and research hospital, mogadishu, somali, between july 2021 and february 2022. the study was reviewed and accepted by the ethics committee of mogadishu somali turkish training and research hospital (ethics protocol no: msth/7128, decision no: 410). informed consent was obtained from all eligible patients or their legal representatives. we adhered to all the principles of the helsinki declaration. 2.2. participants this study included all adult patients who were brought to the ed and required neurological assessment by neurologists in the hospital between july 2021 and february 2022. children and patients with conversion disorders were excluded from the study. table 1: baseline characteristics of studied patients variable number (%) age (years) 20-40 78 (24.3) 40-60 92 (28.7) > 60 150 (46.7) gender male 201 (62.6) female 120 (37.4) comorbidities hypertension 122 (38.0) diabetes mellitus 65 (20.2) stroke 9 (2.8) heart disease 26 (8.1) epilepsy 8 (2.5) respiratory disease 4 (1.2) cancer 4 (1.2) metabolic condition 5 (1.6) without comorbidity 78 (24.3) clinical findings hemiplegia 196 (61.1) consciousness impairment 60 (18.7) paraplegia/quadriplegia 10 (3.1) cranial neuropathy 5 (1.6) aphasia/dysarthria 4 (1.2) cerebellar dysfunction 4 (1.2) hyperkinetic movement disorder 3 (0.9) autonomic dysfunction 1 (0.3) normal neurologic examination 38 (11.8) 2.3. data gathering the data was gathered by a team of neurology specialists and residents in collaboration with emergency physicians. patients’ demographic characteristics, co-morbidities, presentations of neurological diseases in the ed, neurological examination findings, neurological diagnoses made by neurologists, and admission status were evaluated. the neurological diagnosis was made based on clinical, radiological (computed tomography, magnetic resonance imaging, and electroencephalography/electromyography) findings, and other laboratory investigations according to the icd-10 codes. to avoid bias in patient selection, a team of expert physicians, including emergency, neurology, and radiology physicians did collaborative work to ensure correct patient selection and proper diagnosis. 2.4. statistical analyses data was analyzed using spss (statistical package for social sciences, ibm inc., chicago, il, usa) v26.0. descriptive statistics were used to summarize the data; categorical variables were summarized as counts and percentages. the pearson chi-square test was used for the evaluation of categorical data, and the mann–whitney test was used for the evaluation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e20 of quantitative data. the level of significance was chosen as a p-value < 0.05. 3. results 3.1. baseline characteristics of studied patients out of 8,500 patients admitted to the ed during the study period, 321 patients had neurological manifestations requiring neurological evaluation, representing 3.7% of total ed admissions. 189 (59%) patients were above 50 years of age (62.6% male). table 1 shows the baseline characteristics of studied patients. co-morbidities were present in about 243 (76%) of the cases. hypertension was the most common comorbidity among these patients with 122 (38%) cases, followed by diabetes mellitus with 65 (20.2%), and heart diseases with 26 (8.1%) cases. cranial or spinal diagnostic imaging was done in 273 (85%) of the cases. computed tomography was the most common imaging modality used for evaluating these patients. 3.2. clinical characteristics of patients regarding the main reasons for neurology consultations, 141 (44%) were consulted due to altered mental status, 102 (31.8%) for motor weakness, 33 (10%) for seizures, 17 (5.3%) for headache, 9 (2.8%) for vertigo, 8 (2.5%) for speech impairment, 5 (1.6%) due to acute vision loss, and 4 (1.2%) for involuntary movement, while gait impairment and syncope each led to 1 (0.3%) each consultation. on neurological examination, 196 (61%) had hemiplegia, 60 (18.7%) had consciousness impairment, 4 (1.2%) had aphasia/dysarthria, 5 (1.6%) had cranial nerve palsy, 4 (1.2%) had cerebellar dysfunction, 10 (3.1%) had paraplegia, and 38 (11.8%) had normal neurological examination. 3.3. neurological diagnoses the most frequent neurological diagnoses were ischemic strokes with 125 (39%) cases, hemorrhagic strokes with 65 (20.2%), epileptic seizures with 28 (8.7%), and metabolic encephalopathy with 13 (4%) cases (table 2). cerebrovascular disorders were more common in older patients compared to young patients (63% vs. 37%; p = 0.001). in contrast, seizure disorders were more common in young patients than in older patients (68% vs. 32%; p = 0.001). hospital admission was more common in older patients compared to young patients (p = 0.032). one of the most common reasons for neurology consultation was altered mental status. among subjects evaluated due to consciousness impairment, 86 (42%) had ischemic stroke, 65 (31.7%) had hemorrhagic stroke, and 20 (9.7%) were diagnosed with epilepsy (table 2). table 2: neurologic diagnoses among the evaluated patients variable number (%) among all cases ischemic stroke 125 (39.0) hemorrhagic stroke 65 (20.2) epilepsy 28 (8.7) metabolic encephalopathy 13 (4.0) cerebral venous thrombosis 12 (3.7) primary headache 11 (3.4) acute spinal cord disease 10 (3.1) subarachnoid hemorrhage 8 (2.5) benign paroxysmal positional vertigo 7 (2.2) hypertensive encephalopathy 6 (1.9) delirium 6 (1.9) guillain-barre syndrome 4 (1.3) movement disorder 4 (1.3) meningitis 3 (0.9) demyelinating disease 3 (0.9) cns neoplasm 2 (0.6) psychiatric disease 1 (0.3) unspecified cn palsy 1 (0.3) brain abscess 1 (0.3) motor neuron disease 1 (0.3) no definitive diagnosis 6 (1.8) among cases with impaired consciousness ischemic stroke 86 (4.2) hemorrhagic stroke 65 (31.7) epilepsy 20 (9.7) metabolic encephalopathy 10 (4.87) central venous thrombosis 7 (3.4) delirium/dementia 6 (3.0) subarachnoid hemorrhage 3 (1.48) drug intoxication 1 (0.48) hypertensive encephalopathy 1 (0.48) intracranial mass 1 (0.48) meningitis 2 (0.97) brain abscess 1 (0.48) subdural hemorrhage 1 (0.48) undiagnosed 1 (0.48) cns: central nervous system; cn: cranial nerve. 3.4. disposition the median duration of the neurology consultations was 20 minutes. 251 (78%) patients were admitted to the hospital, while 70 (22%) were discharged from the emergency department. after neurology consultation, the neurology department made most of the admissions with 226 (90%) cases, while 25 (10%) were admitted by other departments. of those admitted, 186 (74.2%) were admitted to the neurology ward, and 65 (25.8%) were admitted to the intensive care unit. 4. discussion the findings showed that 3.7% of patients admitted to ed had neurological complaints. hemorrhagic and ischemic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. sheikh hassan et al. 4 strokes were the most prevalent neurological presentations, followed by epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases. the majority of patients with neurological manifestations were admitted to the neurology department. neurological disorders are responsible for more than 20% of the world’s burden of disease. neurological and psychiatric disorders are responsible for up to 28% of all years of life lived with disability. neurologic emergencies contributed to 92 million disability-adjusted life years in 2005 and were predicted to be 103 million in 2030. the burden of these diseases is higher in developing countries, which constitute about 85% of the world’s population (7, 8). neurological disorders account for nearly a quarter of all the years of life spent disabled. in 2005, neurological emergencies resulted in 92 million disability-adjusted life years, with a potential increase to 103 million by 2030. a significant portion of patients in the ed may have lifethreatening neurological diseases that would quickly deteriorate if not diagnosed and treated rapidly. however, the vast majority of these patients are not evaluated by neurologists (9). neurological emergencies are defined by certain features, including rapid onset, the need for immediate assessment, diagnosis, and intervention, and the propensity to cause immediate life-threatening situations or long-term disability (10). because of the shortage of neurology specialists in our country, the majority of patients with neurological emergencies do not have access to neurological evaluation by neurologists. as a result, these patients are assessed by generalists or internists in the ed. in addition, the proportion of neurologic patients in the ed and their diagnosis and disease patterns had never been studied in the country before. as demonstrated by a cross-sectional study conducted in turkey, the mean age of neurologic patients evaluated in the ed was 63.14 ± 18.61 years. male patients comprised 50.7% of the subjects, while female subjects comprised 49.3% (11). according to marcos c. lange, vera l. braatz, and carolina tomiyo et al., the mean age of neurologic patients in the ed was 58 years. 60% of the subjects were female, while 40% were male (12). in our study, most patients were 50 years of age or older (59%). the gender distribution of the study population showed no significant differences, which is consistent with previous studies. comorbidities are common in patients with neurological presentations because of the fact that common neurological disorders become more prevalent with increase in age (13). our study showed that 76% of subjects had associated comorbidities. hypertension was the most common associated comorbidity seen in 38% of the patients, followed by diabetes mellitus, previous history of stroke, heart disease, epilepsy, cancer, respiratory disease, and other metabolic conditions. the findings were similar to those of a study by ufuk emre and his colleagues, which showed that hypertension, previous stroke, diabetes mellitus, chronic obstructive pulmonary disease, epilepsy, and cancer were the most common comorbidities (11). as shown by previous studies, neurological complaints were observed in 2% to 10% of patients admitted to the ed. in one study conducted in brazil, 10% of cases admitted to the ed had neurological presentations [10)(14)another study in turkey found that 6% of emergency admissions were due to neurological disorders (15). as per a study in ethiopia, 10.8% of ed admissions had neurological emergencies (16). in our study, 3.7% of emergency admissions had neurological presentations. 78% of these patients with neurological disorders were admitted to the hospital. this high proportion should be taken into account during emergency medicine and neurology training programs, with the goal of increasing hospital staff’s capacity to diagnose and treat these common neurological disorders. our study also showed that 85% of the cases had at least one cranial or spinal diagnostic imaging. tomography was the most common imaging modality used for evaluating these patients. this indicates the importance of imaging in the diagnosis of neurological diseases. a study in the uk performed by carroll and zajicek demonstrated that the main neurological presentations in the ed requiring neurology consultation were weakness (40%), headache (24%), and seizures (15%). stroke, headaches, and seizures were the three most common ed admissions and accounted for 53% of cases (14). another study conducted in a referral hospital in bangladesh showed that stroke was the most common condition (47.5%), followed by seizure (9.3%), disease of the spinal cord (7.8%), and encephalopathy (6.3%) (17). in our study, the main reason for neurology consultations was impaired consciousness 141 (43.9%), followed by motor weakness 102 (31.8%), seizure 33 (10.3%), and headache 17 (5.3%). this is consistent with the findings that the most common neurological disorders diagnosed in the ed are strokes, seizures, and headache disorders. in the present study, the most common neurological examination findings were motor deficit, consciousness impairment, speech impairment, cranial nerve palsy, cerebellar system dysfunction, abnormal movement disorder, and autonomic dysfunction. these findings are consistent with the fact that cerebrovascular diseases are the most common reason for neurology consultation. this is similar to the findings of another study by sevilay vural and her colleagues, which also showed that motor deficit, speech disorder, consciousness impairment, facial asymmetry, and sensory system dysfunction were the major neurological findings on examination in those subjects (18). in our study, among the evaluated patients, ischemic and hemorrhagic strokes were the most common neurologic dithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e20 agnoses, with 38.9% and 20.2%, respectively. other common diagnoses among these patients included epilepsy (8.7%), cerebral venous thrombosis (3.7%), metabolic encephalopathy (4%), and acute spinal cord disease (3.1%). the distribution of diagnoses among the patients in the ed requiring neurology consultation varies from one study to another. in one study in ethiopia, cerebrovascular diseases, meningitis, and seizure disorders were the most common neurological disorders in the er (16). in another study in nigeria, the main neurologic diagnoses were stroke, central nervous system (cns) infections, and myelopathies (19). in another study conducted in cameroon, malaria and other related central nervous system infections, which are endemic to sub-saharan african countries, were the most common non-traumatic neurological causes in the ed (20). nevertheless, cns infections account for a smaller number of patients in emergency admissions in developed countries (18). although somalia is a sub-saharan african nation, cns infections made up only 0.6% of the cases in our study. according to our study, stroke, movement disorders, cns neoplasm, hypertensive and metabolic encephalopathies, delirium, subarachnoid hemorrhage, and motor neuron diseases were more common in patients over 60 years old. in patients under 60 years old, epilepsy, benign paroxysmal positional vertigo (bppv ), headache disorders, demyelinating disorders, cerebral venous thrombosis (cvt), cns infections, and psychogenic disorders were the most common diseases. our study also showed that the most common neurological findings in patients evaluated due to consciousness impairment were ischemic stroke, hemorrhagic stroke, epilepsy, metabolic encephalopathy, cerebral venous thrombosis, delirium, and drug intoxication. these groups of patients usually receive consultations from the neurology department in the ed. this is almost similar to a study by ufuk emre and his colleagues, which demonstrated that ischemic stroke, hemorrhagic stroke, hypoxic and metabolic encephalopathy were the most common neurologic diagnoses in patients evaluated due to consciousness impairment (11). 5. limitation even though our sample was modest, we only investigated patients admitted to the ed of our hospital. patients in the outpatient clinic were not included in this study; therefore, the neurological disease pattern in outpatient was not studied here. another limitation is the absence of assessment of the outcome and related factors, the short duration of the study, and the fact that it is a single-center cross-sectional study that does not necessarily cover the country’s epidemiology. to avoid bias in patient selection, a team of expert physicians, including emergency, neurology, and radiology physicians, did collaborative work to ensure correct patient selection and proper diagnosis. multi-center studies, including outpatient neurological disease patterns and outcomes, as well as other study designs should be considered. one major strength of this study is it provides an overview assessment of common neurological emergencies in the country (which was missing data), which is why we consider it to be a valuable study. 6. conclusions in our study, neurological emergencies accounted for 3.7% of all emergency admissions. stroke, epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases were the most common neurological disorders. the admission rate was very high following neurological assessment by neurologists. 7. declarations 7.1. acknowledgments we thank all the medical team members at the departments of emergency medicine and neurology of our hospital, including doctors, nurses, the health care experts, and other staff for their assistance in conducting this research. we also thank the patients and their families for their cooperation. in addition, we thank the education and research section of the hospital for their support and encouragement throughout the process of this study. 7.2. conflict of interest the authors declare no conflict of interest 7.3. fundings and supports we did not receive any funding to perform this study. this was completely voluntary research work conducted by the authors of this research paper. 7.4. authors’ contribution all authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. 7.5. data sharing statement the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. sheikh hassan et al. 6 request. 7.6. ethical approval this study was performed in line with the principles of the declaration of helsinki. the study was reviewed and accepted by the ethics committee of mogadishu somali turkish training and research hospital (ethics protocol no: msth/7128, decision no: 410). all patients/caregivers were informed about the purpose of this study. written informed consent was obtained from the patient/relatives during data collection and they signed the consent form. we declare that we have followed the protocols of our work center. patients’ data confidentiality was respected. references 1. kottapally m, josephson sa. common neurologic emergencies for nonneurologists: when minutes count. cleve clin j med. 2016;83(2):116-26. 2. olazarán j, navarro e, galiano m, vaquero a, guillem a, villaverde f, et al. 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consultation systems and tools in the emergency department practice: tele-consultation. cumhuriyet medical journal. 2019;41(2):239-43. 19. owolabi lf, shehu my, shehu mn, fadare j. pattern of neurological admissions in the tropics: experience at kano, northwestern nigeria. annals of indian academy of neurology. 2010;13(3):167. 20. mapoure yn, ongono js, nkouonlack c, beyiha g, mouelle as, luma hn. neurological disorders in the emergency centre of the douala general hospital, cameroon: a cross-sectional study. african journal of emergency medicine. 2015;5(4):165-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusions declarations references emergency. 2017; 5 (1): e70 br i e f re p o rt an echocardiography training program for improving the left ventricular function interpretation in emergency department; a brief report mary jacob1, hamid shokoohi1∗, fabith moideen2, amelia pousson1, keith boniface1 1. department of emergency medicine, george washington university, washington dc. usa. 2. department of emergency medicine, baby memorial hospital, calicut, kerala, india. shokoohi@gwu.edu (corresponding author) received: april 2017; accepted: june 2017; published online: 15 june 2017 abstract: introduction: focused training in transthoracic echocardiography enables emergency physicians (eps) to accurately estimate the left ventricular function. this study aimed to evaluate the efficacy of a brief training program utilizing standardized echocardiography video clips in this regard. methods: a before and after design was used to determine the efficacy of a 1 hour echocardiography training program using powerpoint presentation and standardized echocardiography video clips illustrating normal and abnormal left ventricular ejection fraction (lvef) as well as video clips emphasizing the measurement of mitral valve e-point septal separation (epss). preand post-test evaluation used unique video clips and asked trainees to estimate lvef and epss based on the viewed video clips. results: 21 eps with no prior experience with the echocardiographic technical methods completed this study. the eps had very limited prior echocardiographic training. the mean score on the categorization of lvef estimation improved from 4.9 (95% ci: 4.1-5.6) to 7.6 (95%ci: 7-8.3) out of a possible 10 score (p<0.0001). categorization of epss improved from 4.1 (95% ci: 3.1-5.1) to 8.1 (95% ci: 7.68.7) after education (p<0.0001). conclusion: the results of this study demonstrate a statistically significant improvement of eps’ ability to categorize left ventricular function as normal or depressed, after a short lecture utilizing a commercially available dvd of standardized echocardiography clips. keywords: echocardiography; ultrasonography; ventricular function, left; educational techniques © copyright (2017) shahid beheshti university of medical sciences cite this article as: jacob m, shokoohi h, moideen f, pousson a, boniface k. pan vs. an echocardiography training program for improving the left ventricular function interpretation in emergency department; a brief report . 2017; 5(1): e70. 1. introduction a ssessment of left ventricular function by point-of-care echocardiography is of particular importance in differentiating the causes of some presentation such as hypotension and dyspnea in emergency department. research has demonstrated that focused training in transthoracic echocardiography enables eps to accurately classify left ventricular ejection fraction (lvef) as normal, depressed, or severely depressed (1, 2). over 20 years ago, plummer et al published their sentinel paper on the impact of point-ofcare echocardiography in the evaluation of penetrating car∗corresponding author: hamid shokoohi; 2120 l street nw, suite 450, washington, dc 20037. tel: 202 741 2911 fax: 202 741-2921 e-mail: shokoohi@gwu.edu diac trauma (3). since that time, focused clinician-performed echocardiography has been found to be useful in the assessment of patients with cardiac arrest, suspected massive pulmonary embolism, and hypotension (4, 5). there are several technique for echocardiographic evaluation of lvef, including simpson’s rule, wall motion index, and subjective visual estimation. mcgowan et al. performing a systematic review found that none of the three mentioned methods had superiority to others in estimation of lvef (6). simpson’s method requires significant experience, and can often be limited by technically suboptimal examinations with indistinct endocardial borders. however, visual estimation of lvef is a commonly employed technique and correlates well with ventriculography (7). mitral valve e-point septal separation (epss), is another easy-to-obtain echocardiographic parameter that correlates inversely with lvef. epss is measured as the minimal distance between the anterior mitral this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. jacob et al. 2 valve leaflet and the interventricular septum in the parasternal long view during diastole using m-mode on echocardiography. secko et al. showed that junior eps could obtain epss measurements that correlated with visual estimates of lvef (8). we created a training program in point-of-care echocardiography utilizing echocardiography video clips from patients with known lvef. in this method the trainees were taught to focus on the anterior mitral valve’s motion relative to the septum. the aim of this study was to evaluate the efficacy of this brief educational training program in improving lvef and epss interpretation by eps. 2. methods 2.1. study design and setting a before and after design was used to determine the efficacy of a brief educational echocardiography training program on interpretation of left ventricular function with regards to lvef and epss. the study was conducted in two urban adult academic emergency departments in baby memorial and malabar institute of medical sciences (mims) hospitals in calicut, kerala, india. data were collected during the academic year of 2014-2015. the george washington (gw ) university institutional review board approved the study, and letters of support were obtained from the two participating hospitals in india. both hospitals gave written permission for the study and reviewed the institutional review board forms prior to study commencement. the study investigators were two attending eps and one senior resident from an acgme approved emergency medicine residency training program. no patients were involved and informed consent was obtained from the eps involved in the study. 2.2. participants the study population was the emergency physicians in post graduate training at the mentioned hospitals. all emergency physicians in-training were included in the study and medical students and faculty in practice were excluded. 2.3. outcomes the primary goal of this study was to determine the efficacy of a brief educational training program utilizing standardized echocardiography video clips in improving eps’ skills in categorizing lvef as normal (>50%), depressed (30-50%), or severely depressed (<30%) based upon a single parasternal long axis view. the secondary goal was to classify epss as normal (< 8 mm) or increased (≥ 8 mm) based on b-mode images. 2.4. intervention the eps’ training intervention for estimating lvef and epss consisted of a 1 hour didactic by the senior level emerfigure 1: an m-mode ultrasound scan through the distalmost aspect of the anterior leaflet of the mitral valve to trace the movement of the anterior mv leaflet through the cardiac cycle. the e and a points of each diastole are visible as asymmetric humps during each diastole. gency medicine resident who had previously completed a two-week ultrasound rotation and had undergone dedicated 2 hour echocardiography training with experienced emergency ultrasonographers. the course utilized materials consisting of a powerpoint presentation and a number of standardized video clips illustrating normal and abnormal lvef as well as video clips emphasizing the measurement of epss. the echocardiography video clips were part of a commercially available dvd with patients who had undergone contemporaneous radionuclide ventriculography, giving the lvef. by utilizing a series of standardized examples of a wide range of ejection fractions, the training period was able to be compressed. the epss from the video clips was estimated from the b-mode images using calipers by the gw ultrasound quality assessment team led by an ultrasound fellowship trained attending. epss measurements of > 8 mm indicate poor left ventricular function (figure1). the eps completed a 10 question pre-test and post-test using standardized video clips of parasternal long axis view to estimate lvef and epss based on these video clips from patients with known ejection fraction. each correct answer earned 1 point and inappropriate ones zero point. the preand post-test clips, as well as the video clips in the powerpoint presentation, were all different from one another but had the same number of normal, depressed, and severely depressed lvef videos clips. the preand posttests also reported a survey of broad demographics (year of training, prior ultrasound training, self-reported confidence in echocardiographic interpretation, prior echocardiograms training, and using ultrasound in last month). no personal identifiers were collected in this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e70 2.5. statistical analysis sample size was determined by the class size of international eps. data were analyzed using stata version 10.1 and presented as number (%) or mean ± standard deviation. a paired samples t-test was used to compare two related means. a p-value of less than 0.05 considered significant. 3. results: 32 eps were enrolled in the post graduate em training programs, among them 21 eps (65.62%) were available and participated in both preand post-tests. the baseline characteristics of eps and their previous experiences with ultrasound is summarized in table 1. the eps had very limited prior echocardiographic training aside from the cardiac view of the focused assessment with sonography in trauma (fast) examination. the mean score on the categorization of lvef estimation improved from 4.9 (95% ci: 4.1-5.6) to 7.6 (95%ci: 7-8.3) out of a possible 10 score (p< 0.0001). categorization of epss improved from 4.1 (95% ci: 3.1-5.1) to 8.1 (95% ci: 7.68.7) after education (p<0.0001) (figure 2). 4. discussion the results of this study demonstrate a statistically significant improvement of eps’ ability to categorize left ventricular function as normal or depressed, after a short lecture utilizing a commercially available dvd of standardized echocardiography clips. lvef and epss are important data points in critical care and emergency medicine decision-making. visual estimation skills in this regard typically are gained via many hours of experience at the bedside. in this study, a table 1: demographic characteristic of participants characteristics no (%) year of training 1 8 (38.09) 2 7 (33.33) 3 3 (14.28) not reported 3 (14.28) prior ultrasound training yes 10 (47.61) no 8 (38.09) not reported 3 (14.28) ultrasound use in last month non-user 5 (23.80) user 13 (61.90) not reported 3 (14.28) comfort level not at all 5 (23.80) somewhat 12 (57.14) very 2 (9.52) not reported 2 (9.52) senior emergency medicine resident with skills in focused echocardiography successfully taught a group of eps visual estimation of lvef and epss using a brief training program comprised of commercially available, standardized echocardiography clips, with an emphasis on the motion of the anterior leaflet of the mitral valve as a teaching tool. the ability of eps to accurately categorize lvef has been demonstrated in the past, utilizing an extended period of time with hands-on scanning, both in the echocardiography lab as well as in the ed. moore et al evaluated the ability of eps with focused training in echocardiography to determine left ventricular function of hypotensive emergency department patients compared to a blinded cardiologist reviewing the echocardiogram acquired by the ep (1). training was accomplished with a combination of didactics (six hours of videotaped instruction), time in the echocardiography laboratory under supervision of a cardiologist (greater than ten hours), and completion of complete echocardiogram study reviewed for adequacy by a cardiologist prior to beginning patient enrollment. weighted kappa for the categorization of lvef by eps and cardiology in this study was 0.61 (95% ci 0.39-0.83) and the length of time required for completion of the echocardiogram was 17.5 +/10.8 minutes (range 4-45 minutes). the authors state in their discussion, however, that the majority of the time was spent taking m-mode measurements, border tracing, and capturing adequate views for printing, and they estimate that they could complete a five-view echocardiogram in less than five minutes focusing on lvef. randazzo et al. studied visual estimation of lvef in an ed population as well (2). the investigators undertook additional training in limited echocardiography (three hours of didactics, review of normal and abnormal echocardiograms, and 5 proctored exams on patients who were not enrolled in the study) and compared ep lvef category with that of a complete echocardiogram performed by cardiology. weighted kappa for the categorization of lvef by eps and cardiology was figure 2: lvef and epss interpretation before and after videobased module training (p < 0.0001 for both measurements). lvef=left ventricular ejection fraction; epss=end point septal separation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. jacob et al. 4 0.71 (95% ci 0.53-0.89). subgroup analysis revealed the highest agreement (92.3%) between eps and formal echocardiograms within the normal lvef category, followed by 70.4% agreement in the poor lvef category and only 47.8% in the moderate lvef category. this study is the first to demonstrate that a didactic session utilizing standardized echocardiography clips from patients with known lvef can lead to improved accuracy in the determination of systolic function. improving ep echocardiographic interpretation skills can be beneficial by rapidly identifying those patients with abnormal systolic function, utilizing the motion of the anterior leaflet of the mitral valve as a tool to more accurately assess lvef. this study also evaluated the use of a single view echocardiogram as a physical exam adjunct in distinguishing cardiogenic from non-cardiogenic dyspnea based on ejection fraction (ef) by using a depressed ef as a marker for congestive heart failure as well as epss as a tool for left ventricular function delineation. 5. limitations there were a number of limitations in this study. this study took place in its entirety in the classroom setting, and as such the eps did not acquire the images themselves. image interpretation is a separate skill set than image acquisition, and both facets of point-of-care ultrasound are critical to arriving at the correct diagnosis. in addition, epss is traditionally a measurement made from m-mode. this training session emphasized the concepts of anterior mitral valve leaflet motion relative to the septum that is at the core of the m-mode epss measurement, and these concepts can be applied in real time during b-mode imaging as a component of visual estimation. also, the use of a solitary view of the heart can be deceiving when estimating lvef in the presence of regional wall motion abnormalities. the video clips used in this study were older images from a commercially available digital resource. however, this did not appear to limit the eps’ interpretation of images. the study did not seek to differentiate the incremental increase in diagnostic accuracy of lvef determination with epss compared to without teaching epss, as the sample size was too small to allow two comparison groups. finally, this study did not test long-term retention, which would be the next step in the evaluation of video-based training program as an adjunct to international eps’ ultrasound training. 6. conclusion the results of this study demonstrate a statistically significant improvement of eps’ ability to categorize left ventricular function as normal or depressed, after a short lecture utilizing a commercially available dvd of standardized echocardiography clips. 7. appendix 7.1. acknowledgements the authors wish to thank the faculty at mims and the baby memorial hospitals in calicut for providing opportunity to conduct this research. we are grateful for the academic support of dr. dr.venugopalan poovathum parambil. 7.2. author contribution all authors substantially contributed to this work. m.j., h.s. and k.b. designed the experiment. m.j. and f.m. conducted the observations at the site. m.j. and h.s assembled input data, and conducted statistical analysis. m.j. drafted the first manuscript and all authors discussed the results and implications and commented on the manuscript at all stages. 7.3. funding no funding or support to declare. 7.4. conflict of interest the authors declare that they have no competing interests. the authors do not have a financial interest or relationship to disclose regarding this research project. references 1. moore cl, rose ga, tayal vs, sullivan dm, arrowood ja, kline ja. determination of left ventricular function by emergency physician echocardiography of hypotensive patients. acad emerg med. 2002;9(3):186-93. 2. randazzo mr, snoey er, levitt ma, binder k. accuracy of emergency physician assessment of left ventricular ejection fraction and central venous pressure using echocardiography. acad emerg med. 2003;10(9):973-7. 3. plummer d, brunette d, asinger r, ruiz e. emergency department echocardiography improves outcome in penetrating cardiac injury. ann emerg med. 1992;21(6):709-12. 4. salen p, melniker l, chooljian c, rose js, alteveer j, reed j, et al. does the presence or absence of sonographically identified cardiac activity predict resuscitation outcomes of cardiac arrest patients? the american journal of emergency medicine. 2005;23(4):459-62. 5. blaivas m, fox jc. outcome in cardiac arrest patients found to have cardiac standstill on the bedside emergency department echocardiogram. acad emerg med. 2001;8(6):616-21. 6. mcgowan jh, cleland jg. reliability of reporting left ventricular systolic function by echocardiography: a systematic review of 3 methods. am heart j. 2003;146(3):388-97. 7. cheitlin md, alpert js, armstrong wf, aurigemma gp, beller ga, bierman fz, et al. acc/aha guidelines for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e70 the clinical application of echocardiography. circulation. 1997;95(6):1686-744. 8. secko ma, lazar jm, salciccioli la, stone mb. can junior emergency physicians use e-point septal separation to accurately estimate left ventricular function in acutely dyspneic patients? acad emerg med. 2011;18(11):1223-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion limitations conclusion appendix references emergency. 2017; 5 (1): e72 or i g i n a l re s e a rc h accuracy of endoscopy in predicting the depth of mucosal injury following caustic ingestion; a cross-sectional study athena alipour-faz1, maryam yousefi1, hassan peyvandi2∗ 1. clinical research development center of loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. hearing disorders research center, shahid beheshti university of medical sciences, tehran, iran. received: april 2017; accepted: june 2017; published online: 22 june 2017 abstract: introduction: esophagogastroduodenoscopy (egd) is currently considered as the primary method of determining the degree of mucosal injury following caustic ingestion. the present study aimed to evaluate the screening performance characteristics of egd in predicting the depth of gastrointestinal mucosal injuries following caustic ingestion. methods: adult patients who were referred to emergency department due to ingestion of corrosive materials, over a 7-year period, were enrolled to this diagnostic accuracy study. sensitivity, specificity, positive and negative predictive values as well as negative and positive likelihood ratios of egd in predicting the depth of mucosal injury was calculated using pathologic findings as the gold standard. results: 54 cases with the mean age of 35 ± 11.2 years were enrolled (59.25% male). primary endoscopic results defined 28 (51.85%) cases as second grade and 26 (48.14%) as third grade of mucosal injury. on the other hand, pathologic findings reported 21 (38.88%) patients as first grade, 14 (25.92%) as second, and 19 patients (35.18%) as third grade. sensitivity and specificity of endoscopy for determining grade ii tissue injury were 50.00 (23.04-76.96) and 47.50 (31.51-63.87), respectively. these measures were 100.00 (82.35-100) and 80.00 (63.06-91.56), respectively for grade iii. accuracy of egd was 87.03% for grade iii and 48.14% for grade ii. conclusion: based on the findings of the present study, endoscopic grading of caustic related mucosal injury based on the zargar’s classification has good accuracy in predicting grade iii (87%) and fail accuracy in grade ii injuries (48%). it seems that we should be cautious in planning treatment for these patients solely based on endoscopic results. keywords: caustics; endoscopy, gastrointestinal; pathology; data accuracy © copyright (2017) shahid beheshti university of medical sciences cite this article as: alipour-faz a, yousefi m, peyvandi h. accuracy of endoscopy in predicting the depth of mucosal injury following caustic ingestion; a cross-sectional study . emergency. 2017; 5(1): e72. 1. introduction i ngestion of corrosive substances causes harmful injuries to the upper gastrointestinal tract (1). it is often difficult to estimate the severity of injuries and prognosis of victims based on primary clinical presentation (2). there is a direct correlation between the grade of injury and final outcome (3). technetium 99m sucralfate swallow and endoscopic ultrasonography of gastric wall are successfully used in evaluating and predicting the depth of mucosal injuries related to the ingestion of corrosive material (4, 5). the role of ∗corresponding author: hassan peyvandi; loghman hakim hospital, makhsus street, qazvin street, tehran, iran. email: hassan.peyvandi@gmail.com tel: 00989123260870 computed tomography (ct) scan in determining the depth of injury and estimating the probability of complication following caustic ingestion has been evaluated in some studies (3, 6, 7). bahrami-motlagh and their colleagues declaring the useful role of ct scan as a noninvasive and sensitive screening tool showed the weak correlation of ct and esophagogastroduodenoscopy (egd) regarding the grading of mucosal injury (7). egd is another helpful and available choice in this regard (1, 8). egd is currently considered as the primary method of determining the degree of injury (1, 8-10). zargar’s endoscopic classification is recognized as the most famous and acceptable method to predict the prognosis of corrosive ingestion (1). cheng et al., declared the useful role of egd in predicting short and long term outcomes as well as treatment planning of these patients (11). the present study this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alipour-faz et al. 2 aimed to evaluate the screening performance characteristics of egd in predicting the depth of gastrointestinal mucosal injuries following caustic ingestion. 2. methods 2.1. study design and setting this retrospective cross sectional study (diagnostic accuracy study), was conducted on adult patients who were referred to loghman hakim hospital throughout a 7-year period, from 1999 to 2006, due to corrosive material ingestion. this hospital is known as a toxicology referral center for tehran, iranian capital. the protocol of this study was approved by the ethics committee of shahid beheshti university of medical sciences. researchers adhered to all of helsinki recommendations and confidentiality of patients’ information. 2.2. participants adult patients (≥ 15 years) with available data regarding both endoscopic and pathologic grading of mucosal injury following caustic ingestion were enrolled to the study. patients with obvious surgical indications such as acute peritonitis, pneumo mediastinitis and neck emphysema, who underwent emergent surgical interventions, as well as those with normal or grade i injury on endoscopic findings were excluded. since grade i mucosal damage could be approached noninvasively and grade iv usually underwent emergent surgical interventions, only patients with grade ii and iii mucosal injury were enrolled. 2.3. data gathering patients’ data consisted of baseline variables (age, sex) as well as results of endoscopic and pathologic grading of mucosal injuries, which were collected from patients’ profiles using a predesigned checklist by a senior surgery resident. all endoscopies were performed by expert gastroenterologists within 24 hours of corrosive material ingestion. tissue biopsies were sent to pathologists who were blind to endoscopic findings in order to report the grading of mucosal damages. modified zargar’s endoscopic classification for caustic injuries has been used for endoscopic grading (1). 2.4. statistical analysis data were analyzed using spss version 20. findings were reported as mean ± standard deviation or frequency and percentage. screening performance characteristics of egd endoscopy consisted of sensitivity, specificity, positive and negative predictive values as well as negative and positive likelihood ratios, which were calculated using med calc 14 software and reported with 95% confidence interval (ci). pathologic findings regarding the grade of injuries were considered as the gold standard. accuracy of 90 100 was considered as excellent, 80 – 90 as good, 70 – 80 fair, 60 – 70 poor, and < 60 fail. 3. results 118 patients referred to emergency department following caustic ingestion during the study period. 19 (16.10%) patients underwent emergent laparotomy and 99 (83.89%) underwent egd endoscopy (45 grade i and 54 grade ii and iii). finally 54 cases with the mean age of 35 ± 11.2 years were enrolled in the study (59.25% male). primary endoscopic results defined 28 (51.85%) cases as second grade and 26 (48.14%) as third grade of mucosal injury. on the other hand, pathologic findings reported 21 (38.88%) patients as first grade, 14 (25.92%) as second grade, and 19 patients (35.18%) as third grade of mucosal injury. table 1 shows the screening performance characteristics of egd endoscopy for detection of second and third degree mucosal damage following caustic ingestion. accuracy of egd endoscopy was 87.03% for grade iii and 48.14% for grade ii. 4. discussion based on the findings of the present study, endoscopic grading of caustic related mucosal injury based on the zargar’s classification has good accuracy in predicting grade iii (87%) and fail accuracy in grade ii injuries (48%). it seems that we should be cautious in planning treatment for these patients solely based on endoscopic results. there has not been any consensus regarding a standard method in evaluating the severity of injury after ingestion of corrosive material. in spite of current controversies, egd has been known as the most decisive method for evaluating the mucosal damages (12). egd is safe concerning the perforation risk 12 to 72 hours post ingestion injury but should be avoided between the 5th and 15th days post ingestion (1, 8, 9). however, defining the depth of damage by inspecting the dead epithelium is difficult. there are also some limitations regarding precise diagnosis, especially in first and second grade injuries. moreover, in the presence of damage to proximal third of the esophagus, endoscopy of distal parts and stomach would be impossible (13). in the observational study of cabral et al. all patients with one week bad outcome had initial severe grading of injury in their emergency endoscopy (14). the sensitivity of endoscopy in predicting the grades 2b and 3 of mucosal damage were 100% and 80% and its specificity were 38% and 37% in the study by lurie et al. (15). based on the findings of the present study and considering the low sensitivity and specificity of endoscopy in estimation of the depth of grade ii tissue injuries, it seems that making a decision regarding a treatment plan for these patients solely based on the results of endoscopic grading is not accurate. in other words, out of the 28 patients that had a grade ii tissue injury according to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e72 table 1: screening performance characteristics of endoscopy in grading of mucosal injuries following caustic ingestion with 95% confidence interval (ci) characteristics grade ii (95% ci) grade iii (95% ci) sensitivity 50.00 (23.04-76.96) 100.00 (82.35-100) specificity 47.50 (31.51-63.87) 80.00 (63.06-91.56) positive predictive value 25.00 (10.69-44.87) 73.08 (52.21-88.43) negative predictive value 73.08 (52.2-88.43) 100.00 (87.66-100) positive likelihood ratio 0.95 (0.52-1.74) 5.00 (2.58-9.70) negative likelihood ratio 1.05 (0.57-1.95) 0.00 (0.00-nan) nan: the calculation cannot be performed because the values entered include one or more instances of zero. endoscopy results, 21 were placed in grade iii after pathology evaluations; therefore, it can be said that relying on endoscopy findings would have led to 75% underestimation of injuries in these patients. on the other hand, only 7 out of the 14 cased that were identified as grade ii via pathology had been correctly identified via endoscopy and the other 7 cases were wrongly identified as grade iii. this means that about 50% overestimation had occurred in this regard. however, regarding grade iii injuries, endoscopy had a higher accuracy. considering its 100% sensitivity, it can be considered as a proper screening tool for grade iii injuries. in other words, all of the 19 cases that were identified as grade iii injuries via pathology had been correctly identified via endoscopy and out of the 26 cases identified as grade iii injuries via endoscopy, only 7 (26.9%) were false positive cases. based on our findings, we should seek new methods with better diagnostic power to evaluate the depth of injury due to corrosive ingestion. since third grade injury accompanies clinical signs and symptoms and demands emergent surgical intervention, egd would be an acceptable diagnostic tool for third grade injuries; whilst in second grade damage, egd alone is not sufficient to evaluate the depth of damage. therefore, we recommend other diagnostic tools such as thechnetium-99 pyrophosphate scintigraphy and endoscopic ultrasonography in order to increase the diagnostic precision of egd in grade ii injuries (16, 17). finally, our findings show that egd is not accurate in defining the depth of a mild damage after corrosive agent ingestion, so the treatment approach should not be based on egd findings; but in severe damages, egd is accurate in evaluating the depth of damage. overall, we need accurate and precise tools to evaluate the depth of damage in lower grades of caustic injuries. 5. limitation carrying out the study in a retrospective manner and based on the data available in the profiles was among the most important limitations of this study. in addition, the sample size was determined based on the available cases during a determined period and this might have affected the final power of the results. therefore, repeating this study in a prospective manner and with a higher number of patients can be helpful. 6. conclusion based on the findings of the present study endoscopic grading of caustic related mucosal injury based on the zargar’s classification has good accuracy in predicting grade iii (87%) and fail accuracy in grade ii injuries (48%). it seems that we should be cautious in planning treatment for these patients solely based on endoscopic results. 7. appendix 7.1. acknowledgements we would like to appreciate the support of clinical research development center of loghman hakim hospital and hearing disorder research center, shahid beheshti university of medical sciences, tehran, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. zargar sa, kochhar r, mehta s, mehta sk. the role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. gastrointest endosc. 1991;37(2):165-9. 2. keh sm, onyekwelu n, mcmanus k, mcguigan j. corrosive injury to upper gastrointestinal tract: still a major surgical dilemma. world journal of gastroenterology: wjg. 2006;12(32):5223. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alipour-faz et al. 4 3. rigo g, camellini l, azzolini f, guazzetti s, bedogni g, merighi a, et al. what is the utility of selected clinical and endoscopic parameters in predicting the risk of death after caustic ingestion? endoscopy. 2002;34(04):304-10. 4. millar ajw, numanoglu a, mann m, marven s, rode h. detection of caustic oesophageal injury with technetium 99m-labelled sucralfate. j pediatr surg. 2001;36(2):262-5. 5. gastric stenosis in severe corrosive gastritis: prognostic evaluation by endoscopic ultrasonography. clin toxicol. 2007;45(3):284-6. 6. caustic injury: can ct grading system enable prediction of esophageal stricture? clin toxicol. 2010;48(2):137-42. 7. bahrami-motlagh h, hadizadeh-neisanghalb m, peyvandi h. diagnostic accuracy of computed tomography scan in detection of upper gastrointestinal tract injuries following caustic ingestion. emergency. 2017;5(1):e61. 8. keh sm, onyiioc n, mcmanus k, mcguigan j. corrosive injury to upper gastrointestinal tract: still a major surgical dilemma. world journal of gastroenterology. 2006;12(32):5223. 9. cheng h-t, cheng c-l, lin c-h, tang j-h, chu y-y, liu n-j, et al. caustic ingestion in adults: the role of endoscopic classification in predicting outcome. bmc gastroenterology. 2008;8(1):1. 10. poley j-w, steyerberg ew, kuipers ej, dees j, hartmans r, tilanus hw, et al. ingestion of acid and alkaline agents: outcome and prognostic value of early upper endoscopy. gastrointest endosc. 2004;60(3):372-7. 11. cheng h-t, cheng c-l, lin c-h, tang j-h, chu y-y, liu n-j, et al. caustic ingestion in adults: the role of endoscopic classification in predicting outcome. bmc gastroenterol. 2008;8(1):31. 12. temiz a, oguzkurt p, ezer ss, ince e, hicsonmez a. predictability of outcome of caustic ingestion by esophagogastroduodenoscopy in children. world j gastroenterol. 2012;18(10):1098-103. 13. cello jp, fogel rp, boland cr. liquid caustic ingestion spectrum of injury. archives of internal medicine. 1980;140(4):501-4. 14. cabral c, chirica m, de chaisemartin c, gornet j-m, munoz-bongrand n, halimi b, et al. caustic injuries of the upper digestive tract: a population observational study. surg endosc. 2012;26(1):214-21. 15. the role of chest and abdominal computed tomography in assessing the severity of acute corrosive ingestion. clin toxicol. 2013;51(9):834-7. 16. aksu b, durmus-altun g, ustun f, torun n, kanter m, umit h, et al. a new imaging modality in detection of caustic oesophageal injury: technetium-99m pyrophosphate scintigraphy. international journal of pediatric otorhinolaryngology. 2009;73(3):409-15. 17. chiu h-m, lin j-t, huang s-p, chen c-h, yang c-s, wang h-p. prediction of bleeding and stricture formation after corrosive ingestion by eus concurrent with upper endoscopy. gastrointestinal endoscopy. 2004;60(5):827-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e68 or i g i n a l re s e a rc h intravenous lidocaine versus morphine sulfate in pain management for extremity fractures; a clinical trial arash forouzan1, hassan barzegari1, hassan motamed1∗, ali khavanin1, hamideh shiri1 1. emergency medicine department, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: april 2017; accepted: may 2017; published online: 28 may 2017 abstract: introduction: considering the existing contradictions regarding effectiveness of intravenous (iv ) lidocaine, especially in emergency department (ed), the present study was designed to compare the analgesic effect of iv lidocaine and morphine sulfate in pain management for extremity bone fractures. methods: in this triple blind clinical trial, 15 to 65 year-old patients with extremity fractures and in need of pain management were randomly allocated to either iv lidocaine or morphine sulfate group and were compared regarding severity of pain 5, 10, 15, 20, 25, and 30 minutes after infusion via intention to treat analysis. the absolute risk reduction, number needed to treat and relative risk of iv lidocaine after 30 minutes were 0.40 (95%ci: 0.25 – 0.64), 7 (95%ci: 3.7 – 23.1), and 20.71 (95%ci: 10.91 – 30.51), respectively. results: 280 patients with the mean age of 32.50 ± 12.77 years were randomly divided into 2 equal groups of 140 (73.9% male). the 2 groups had similar baseline characteristics. 15 minutes success rate was 49.28% in lidocaine and 33.57% in morphine sulfate group (p = 0.011), and after 30 minutes it reached to 85.71% and 65.00%, respectively (p < 0.001). conclusion: based on the results of the present study, iv lidocaine could be considered as a reasonable alternative choice for pain management in ed. keywords: lidocaine; morphine; pain management; emergency service, hospital; fractures, bone © copyright (2017) shahid beheshti university of medical sciences cite this article as: forouzan a, barzegari h, motamed h, khavanin a, shiri h. intravenous lidocaine versus morphine sulfate in pain management for extremity fractures; a clinical trial. emergency. 2017; 5(1): e68. 1. introduction p ain is an unpleasant mental and sensory experience that often occurs after a tissue injury and secretion of inflammatory cytokines (1). various methods, such as using opioids and non-steroid anti-inflammatory drugs, topical anesthetics and regional nerve block are applied for pain management (2-6). intravenous (iv ) infusion of lidocaine is one of the methods used by anesthesiology specialists for induction of analgesia (7-11). lidocaine is a relatively safe drug in the amide group, which acts as an analgesic, anti-hyperalgesia and anti-inflammatory agent in low doses and is affective in relieving neuralgia, burn and procedural pains (12). this drug induces its analgesic effects via stimulating secretion of anti-inflammatory cytokines (interleukin1) receptor antagonist and blocking central and peripheral ∗corresponding author: hassan motamed; emergency medicine department, ahvaz jundishapur university of medical sciences, golestan avenue, ahvaz, khuzestan province 6135733118, iran; tel/fax: +986133743099; email:hasan_motamed@yahoo.com voltage-dependent sodium channels (13). in cases that opioids lack efficient effectiveness, iv injection of lidocaine has been used as a proper replacement (12, 14, 15). although many studies have indicated the role of iv lidocaine in pain relief after trauma or surgery and decrease in the need for other opioids, there are also studies that do not agree (7). for example, in one study continuous infusion of low doses of lidocaine, had not reduced use of other analgesics (16). in addition, for induction of analgesia after tonsillectomy surgery, infusion of iv lidocaine did not play an effective role in reducing pain after surgery (17). therefore, considering the limited number of studies on the effect of iv lidocaine in pain management, especially in emergency department (ed) and the existing contradictions regarding its effectiveness, the present study was designed with the aim of assessing the analgesic effect of iv lidocaine compared to iv morphine sulfate in relieving the pain caused by traumatic extremity bone fractures. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. forouzan et al. 2 2. methods 2.1. study design the present clinical trial was carried out during a 6 month period from june 2016 to nov 2016 on patients presenting to ed of imam khomeini and golestan hospitals in ahvaz, iran, who needed pain management due to traumatic bone fractures. before including the patients in the study, informed consent was obtained from them and they were given explanations regarding the study process. throughout all steps of the study, the researchers adhered to the principles of helsinki declaration and confidentiality of patient data. all costs of the project were covered by the researchers and no additional costs were inflicted on the patients. this study was approved by the ethics committee of ahvaz university of medical sciences and has been registered on iranian registry of clinical trials under the number irct2015052622423n1. 2.2. participants the study population consisted of patients aged 15 to 65 years who had fractures in the long bones of their upper or lower extremities and the fracture was evident in physical examination and the patient needed pain management (moderate to severe pain). pregnant and lactating women; patients with altered level of consciousness; hemodynamic instability; evidence of intra-abdominal or pelvic hemorrhage; mental retardation; history of allergy to lidocaine or morphine; history of addiction; underlying illness (coronary artery problems, valvular disorders, arrhythmia, hypertension, cerebrovascular diseases, seizure, diabetes, liver or kidney diseases); and consuming cardiac drugs were excluded from the study. no limitations were considered regarding sex and fracture type and being open or closed fracture. physical examination and patient selection was done by a senior emergency medicine resident and a senior orthopedics resident. 2.3. intervention after selecting the patients that met the inclusion criteria of the study, they were divided into 2 groups receiving either iv lidocaine (1.5 mg/kg during 2 minutes) or iv morphine sulfate (0.1 mg/kg during 2 minutes). the study was designed as a triple blind manner as the patient, the person injecting the drug, and data analyzer were all blind to the type of drug consumed. both drugs were colorless and odorless and to make them look alike, both drugs were injected in a 10cc volume with syringes with the same shape and color. injection was performed by either an emergency medicine specialist or a senior resident of emergency medicine under complete cardiac, respiratory, blood pressure, level of consciousness and pulse oximetry monitoring. before the injection of drug, vital signs of the patient and their pain score using visual analog scale (vas) were measured and recorded. 2.4. data gathering a checklist consisting of demographic data (age, sex), vital signs (number of breaths per minute, systolic and diastolic blood pressures, heart beats per minute, and oxygen saturation percentage) and pain severity on presentation and 5, 10, 15, 20, 25, and 30 minutes after injection was filled for all the patients. the senior emergency medicine resident in charge of the patient was responsible for gathering the data, but evaluation of vital signs of the patient was performed by someone other than the one injecting the drugs, who was blind to the type of drug used. to measure pain severity, vas scale was used. pain score of 3 to 6 was considered as moderate pain and score ≥6 was considered as severe pain. at least 3 points drop in pain score was considered as success in pain management. if pain was still present after 30 minutes, iv fentanyl with 1.5 mg/kg dose was prescribed for the patients as bolus. 2.5. outcome at least 3 scores drop in pain severity was considered as success and less than 3 scores as failure in treatment on 15th and 30th minutes. in addition, patients were assessed regarding manifestation of any side effects such as confusion; tremor; stupor; seizure; restlessness; anxiety; lethargy; sleepiness; hallucination; strabismus; syncope; hypotension; bradycardia; cardiac failure; new arrhythmia; cardiac failure; anaphylaxis; status asthmaticus; edema; nausea; vomiting; rash and tinnitus. it was determined that in case of any drug side effects, the patient should be excluded from the study and be rapidly treated for relieving the side effect. 2.6. statistical analysis non-probability convenience sampling was used and analysis of data was done with intention to treat method via spss 21 statistical software. quantitative variables were reported as mean ± standard deviation (sd), and qualitative data as frequency and percentage. to report the effectiveness of the drug, absolute risk reduction (arr), number needed to treat (nnt) and relative risk (rr) were used with 95% ci. to do comparisons between the 2 groups, chi square and t-test were used. p < 0.05 was considered as level of significance. 3. results 280 patients with the mean age of 32.50 ± 12.77 years (15 65) were randomly divided into 2 equal groups receiving either iv lidocaine (140 patients) or morphine sulfate (140 patients) (73.9% male). table 1 compares baseline data of the participants in the 2 groups. the 2 groups had similar characteristics regarding pain severity and vital signs on admisthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e68 table 1: comparison of baseline patients’ data in the 2 study groups on admission to emergency department variable groups p value iv* lidocaine iv* morphine age (year) 31.47 ± 12.31 33.53 ± 13.16 0.178 sex male 104 (50.2) 103 (49.8) 0.500 female 36 (49.3) 37 (50.7) pain severity moderate 12 (8.6) 17 (12.1) 0.434 severe 128 (91.4) 123 (87.9) heart rate (per minute) 89.06 ± 6.98 88.19 ± 8.98 0.328 respiratory rate (per minute) 17.93 ± 1.69 18.30 ± 1.81 0.078 systolic blood pressure (mmhg) 123.85 ± 11.68 124.5 ± 13.46 0.667 diastolic blood pressure (mmhg) 76.21 ± 6.90 77.26 ± 9.09 0.281 oxygen saturation (%) 98.46 ± 0.76 98.36 ± 0.71 0.293 ∗iv: intravenous; data are presented as frequency and percentage or mean ± standard deviation. pain severity is shown based on vas score. table 2: comparing the pain severity of the patients between the 2 studied groups in the initial 30 minutes after intravenous (iv ) injection of the drug pain severity study groups; no (%) p value iv lidocaine iv morphine 15 minutes mild 10 (7.1) 10 (7.1) moderate 70 (50.0) 66 (47.1) 0.884 severe 60 (42.9) 64 (45.8) 30 minutes mild 51 (36.4) 37 (27.1) moderate 58 (41.5) 61 (43.6) 0.186 severe 31 (22.1) 41 (29.3) table 3: effectiveness characteristics of intravenous lidocaine in pain management of patients with extremity fractures characteristics values (95% ci) after 15 minutes after 30 minutes ms failure rate 66.43% 35.00% lidocaine failure rate 50.71% 14.29% relative risk 0.76 (0.62 – 0.93) 0.40 (0.25 – 0.64) absolute risk reduction 15.72 (4.33 – 27.11) 20.71 (10.91 – 30.51) number needed to treat 5 (3.3 – 9.2) 7 (3.7 – 23.1) ms: morphine sulfate sion to ed. table 2 and figure 1 depict the rate of decrease in pain severity in the 2 studied groups at various times after iv injection. success rate in decreasing pain severity (at least 3 points) 15 minutes after injection was 49.28% (69 individuals) in lidocaine group and 33.57% (47 patients) in morphine sulfate group (p = 0.011), and 30 minutes after injection, these numbers were 85.71% (120 patients) and 65.00% (91 individuals), respectively (p < 0.001). no cases of hypotension, respiratory depression, dysrhythmia and drop in arterial oxygen saturation were detected in either group during the initial 30 minutes after drug injection. 4. discussion based on the results of the present study, success rate of iv lidocaine in relieving the pain caused by extremity fractures was significantly higher than that of morphine sulfate, 15 and 30 minutes after injection. other indices of effectiveness such as rr, arr and nnt also confirmed the proper effect of iv lidocaine for management of acute pain. in addition, no drug side effect was detected in either group. while about half of the patients who received iv lidocaine experienced at least 3 points drop in their pain score during the first 15 minutes after injection, this rate was 33% for the group rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. forouzan et al. 4 figure 1: changes in pain severity measures in the 2 studied groups at different times after intravenous injection of the drug. ceiving iv morphine. in other words, using lidocaine led to 15% to 20% drop in unsuccessful pain management cases 15 and 30 minutes after injection. relative risk or risk ratio of using lidocaine 15 and 30 minutes after injection were 0.40 and 0.76, respectively. in other words, the probability of not controlling the pain in lidocaine group relative to morphine sulfate group was less than 1, which confirms its higher effectiveness. numerous studies have confirmed the effectiveness of iv lidocaine for successful pain management and its role in decreasing the need for opioid use (12, 14, 15). low dose of iv lidocaine has been safer and more effective than regional analgesia in relieving pain caused by forearm fracture in children (18). a clinical trial by el-tahan et al. in 2009 showed that iv lidocaine prescription before cesarean section surgery leads to less increase in heart rate, average arterial pressure and concentration of plasma cortisol. their findings indicated that iv lidocaine can be considered as a safe and effective choice for reducing stress response of the mother to surgery during cesarean delivery (19). findings of yardeni et al. in 2009 showed that injection of iv lidocaine before and during surgery can be effective in improvement of pain management after surgery as well as reduction of immune interference and release of pain and inflammation inducing mediators due to surgery (20). need for morphine sulfate in the first 72 hours post operation was lower in the group that had received iv lidocaine before surgery (21). based on the findings of the present study, it seems that iv lidocaine has proper effectiveness in controlling acute pain caused by extremity fractures. probably, the main reason for the low rate of using this option for pain management in ed is fear of side effects such as dysrhythmia. it seems that since most of the patients participating in the present study were either young or in their midlife, the probability of showing cardiac side effects was naturally lower. it seems more logical to decide on the side effects of injecting the drug after studies on various age groups and considering their various underlying illnesses. if the results of the present study are confirmed in other studies, we can count on iv lidocaine as an option and proper replacement for pain management of patients in ed. 5. limitation longer follow up of the patients and calculating the patients’ need for using analgesics after probable relapses are among the points that can decrease the limitations of the present study. measuring serum level of lidocaine to avoid reaching toxic levels of the drug can also be considered in future studies. repeating the study in populations with various age ranges and considering various types of underlying illnesses can be beneficial. in addition, for a more accurate comparison, fracture types and their location should better be homogenized between the 2 groups. however, random allocation of the patients prevented this confounding factor affecting the results to a great extent in the current study. 6. conclusion based on the results of the present study, success rate of iv lidocaine in relieving pain caused by extremity fracture was significantly higher than iv morphine. using lidocaine led to 20% decrease in unsuccessful pain management cases until 30 minutes after injection with risk ratio of 0.76. 7. appendix 7.1. acknowledgements none 7.2. author contribution all the authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support none 7.4. conflict of interest none references 1. wu cl, raja sn. treatment of acute postoperative pain. the lancet. 2011;377(9784):2215-25. 2. koppert w, weigand m, neumann f, sittl r, schuettler j, schmelz m, et al. perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e68 consumption after major abdominal surgery. anesthesia & analgesia. 2004;98(4):1050-5. 3. mccarthy gc, megalla sa, habib as. impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery. drugs. 2010;70(9):1149-63. 4. joris j, kaba a, lamy m. transition between anesthesia and post-operative analgesia: relevance of intraoperative administration of analgesics. acta anaesthesiologica belgica. 2000;52(3):271-9. 5. choi sj, kim mh, jeong hy, lee jj. effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery. korean journal of anesthesiology. 2012;62(5):429-34. 6. grady p, clark n, lenahan j, oudekerk c, hawkins r, nezat g, et al. effect of intraoperative intravenous lidocaine on postoperative pain and return of bowel function after laparoscopic abdominal gynecologic procedures. aana journal. 2012;80(4). 7. gordon d, faan m, schroeder m. intravenous lidocaine for postoperative analgesia: renewed interest in an old strategy. am pain soc bull. 2008;18:3-5. 8. cepeda ms, delgado m, ponce m, cruz ca, carr db. equivalent outcomes during postoperative patientcontrolled intravenous analgesia with lidocaine plus morphine versus morphine alone. anesthesia & analgesia. 1996;83(1):102-6. 9. kaba a, laurent sr, detroz bj, sessler di, durieux me, lamy ml, et al. intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy. the journal of the american society of anesthesiologists. 2007;106(1):11-8. 10. mckay a, gottschalk a, ploppa a, durieux me, groves ds. systemic lidocaine decreased the perioperative opioid analgesic requirements but failed to reduce discharge time after ambulatory surgery. anesthesia & analgesia. 2009;109(6):1805-8. 11. martin f, cherif k, gentili me, enel d, abe e, alvarez jc, et al. lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty. the journal of the american society of anesthesiologists. 2008;109(1):118-23. 12. wasiak j, mahar p, mcguinness sk, spinks a, danilla s, cleland h. intravenous lidocaine for the treatment of background or procedural burn pain. the cochrane library. 2012. 13. farag e, ghobrial m, sessler di, dalton je, liu j, lee jh, et al. effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. the journal of the american society of anesthesiologists. 2013;119(4):932-40. 14. beaudoin fl, haran jp, liebmann o. a comparison of ultrasound-guided three-in-one femoral nerve block versus parenteral opioids alone for analgesia in emergency department patients with hip fractures: a randomized controlled trial. academic emergency medicine. 2013;20(6):584-91. 15. sahota o, rowlands m, bradley j, van de walt g, bedforth n, armstrong s, et al. femoral nerve block intervention in neck of femur fracture (finof): study protocol for a randomized controlled trial. trials. 2014;15(1):189. 16. insler sr, o’connor m, samonte af, bazaral mg. lidocaine and the inhibition of postoperative pain in coronary artery bypass patients. journal of cardiothoracic and vascular anesthesia. 1995;9(5):541-6. 17. striebel h, klettke u. is intravenous lidocaine infusion suitable for postoperative pain management? schmerz (berlin, germany). 1992;6(4):245-50. 18. juliano pj, mazur jm, cummings rj, mccluskey wp. lowdose lidocaine intravenous regional anesthesia for forearm fractures in children. journal of pediatric orthopedics. 1992;12(5):633-5. 19. el-tahan mr, warda om, diab dg, ramzy ea, matter mk. a randomized study of the effects of perioperative i.v. lidocaine on hemodynamic and hormonal responses for cesarean section. journal of anesthesia. 2009;23(2):215-21. 20. yardeni iz, beilin b, mayburd e, levinson y, bessler h. the effect of perioperative intravenous lidocaine on postoperative pain and immune function. anesthesia and analgesia. 2009;109(5):1464-9. 21. koppert w, weigand m, neumann f, sittl r, schuettler j, schmelz m, et al. perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. anesthesia and analgesia. 2004;98(4):1050-5, table of contents. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e62 or i g i n a l re s e a rc h comparing the outcomes of surgical and non-surgical approaches in management of older patients with distal radius fracture; a retrospective cohort study mehdi teimouri 1, milad ghaderi2∗, saeed hatami1 1. department of orthopedic surgery, kashani university hospital, school of medicine, isfahan university of medical science, isfahan, iran. 2. school of medicine, isfahan university of medical sciences, isfahan, iran. received: may 2022; accepted: june 2022; published online: 2 august 2022 abstract: introduction: distal radius fractures (drfs) are the most common orthopedic injuries in emergency department. this study aimed to compare the outcomes of conservative and surgical managements of drfs in the aged population. methods: in this retrospective cohort study, ninety patients with unilateral drfs were treated using either surgical or conservative (casting) approach and the management outcomes as well as complications were compared between the two groups at 3 and 6-month follow-ups. results: a total of 90 patients over 70 years old were included (45 treated with cast immobilization, and 45 using the surgical method). the mean age (p = 0.56) and gender (p = 0.85) was similar in the two groups. except for quality of life in both follow-up times, patients treated with surgical methods showed better outcomes in other aspects, including 3-month (p = 0.042) and 6-month (p = 0.022) mean disability of the arm shoulder hand (dash) score, 3-month (p = 0.013) and 6-month (p = 0.006) mean range of motion (rom), and 3-month (p = 0.003) and 6-month (p = 0.033) pain intensity based on visual analogue scale (vas). a total of 70 (77.77%) adverse events were registered (33 (36.6%) in the casting group and 37 (41.1%) in the surgical group; p = 0.05). the rate of mal-union (p = 0.021) and superficial radial nerve injury (p = 0.026) were significantly lower in the surgical group. conclusion: the findings suggest that surgical approach for management of drfs in elder cases has better clinical and functional outcomes than cast immobilization. keywords: conservative treatment; radius fractures; casts, surgical; aged; disabled persons cite this article as: teimouri m, ghaderi m, hatami s. comparing the outcomes of surgical and non-surgical approaches in management of older patients with distal radius fracture; a retrospective cohort study. arch acad emerg med. 2022; 10(1): e62. https://doi.org/10.22037/aaem.v10i1.1606. 1. introduction distal radius fractures (drfs) are among the most common orthopedic injuries, with over 640,000 cases reported during 2001 in the us alone. this type of fracture accounts for up to 18% of all fractures in the elderly age group (1). epidemiological studies point out that the highest incidences are found in children and the elderly people with the elderly group (over 65 years old) making up more than 50% of all drf cases in the population (2). the age-adjusted incidence in large studies ranges from 73 to 202 per 100,000 in men and from 309 to 767 per 100,000 in women among adults over 50 years old ∗corresponding author: milad ghaderi; school of medicine, isfahan university of medical sciences, isfahan, iran. tel: +98-9136886840, email: miladghaderi6@gmail.com, orcid: https://orcid.org/0000-0002-6487-5469. (2). an, peripheral low-energy fracture is a strong indication of osteoporosis (3). patients with distal radius fracture have been found to carry twice the risk of a later hip fracture (4). in older adults, especially females, the fracture results from lowenergy or moderate trauma, such as falling from a standing height. and some studies showed that there is an increased tendency to fall among patients over 65 years old (5). this indicates that greater fragility of the bone, resulting from osteoporosis and osteopenia, in combination with an increased tendency to fall are major risk factors for distal radius fractures, along with other risk factors such as prior forearm or vertebral fractures, loss of body height, cigarette smoking, and medical treatment for certain diseases (e.g. rheumatoid arthritis) (5, 6). there are several surgical options for this kind of injury, and each option has its advantages and complications. the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. teimouri et al. 2 american academy of orthopedic surgeons is currently unable to recommend any specific treatment, whether conservative or surgical. in the latter case, they also do not suggest which surgical approach is best (7). choice of treatment depends on many factors, such as the patient’s age, lifestyle, associated medical conditions, compliance, functional demands, limb dominance, type of fracture, severity, and alignment of the fracture, condition of the soft tissue, and concomitant fractures (8, 9). in the last century, most distal radius fractures in adults were treated non-operatively (conservatively) by reducing the fracture when displaced and stabilization in a plaster cast or other external brace. the results of such treatment, particularly in older people with bones weakened by osteoporosis, are not consistently satisfactory (10). treatment by closed reduction and cast immobilization can be carried out on a large scale, at low expense, and without admission; however, this often leads to poor radiological results and displacement, the rate of which can be as high as 40% (11). this has resulted in attempts to develop surgery strategies aimed at more accurate reduction and more reliable stabilization. several surgical options for distal radius fractures have been described, such as percutaneous pinning and casting (closed reduction) (12) and external fixation (12, 13); open reduction internal fixation (orif) using the volar locking plate technique represents the most chosen option, orif with herbert screw fixation and crif with k-wire (13, 14). percutaneous pinning involves percutaneous (through the skin) insertion of pins, which may be threaded or wired (12). in external fixation, which is also a closed, minimally invasive method, metal pins or screws are driven into bone, generally via small skin incisions, after drilling them on either side of the fracture. these pins are then fixed externally with a plaster cast or an external fixator frame (12, 13). for both methods, fracture reduction is generally closed (15). internal fixation, which is usually preceded by open reduction, involves open surgery, where the fractured bone is exposed to direct view. given the invasive and technically demanding nature of open surgery, with the increased risks of infection and soft-tissue damage, internal fixation is usually reserved for more severe injuries. it is, however, an increasingly used method of surgery (16). amongst these surgical methods, volar locking plate systems (vlps) offer predictable outcomes, especially in osteoporotic patients, and their use is increasingly popular (17-20). there is also a paucity of evidence on the optimal treatment of distal radius fractures in the iranian population. this study aimed to compare the clinical and functional outcomes as well as quality of life of older patients with drf between two treatment approaches of cast immobilization and surgery. 2. methods 2.1. study design and setting a retrospective cohort study on 90 ageand gender-matched patients treated for drf at two different referral hospitals (alzahra and kashani) in isfahan, iran, was conducted between 2020 and 2021. patients were either treated with surgical or conservative (casting) approaches due to different variables (i.e., associated medical conditions, type of fracture, severity and alignment of the fracture, surgical method, surgeon technique, and experience) and the management outcomes as well as complications were compared between groups at 3 and 6-month follow-ups. ethical code ir.mui.med.rec.1399.1005 was obtained from isfahan university of medical sciences. consents were obtained from all patients. researched adhered to confidentiality of patients’ data and ethical recommendations in the declaration of helsinki. 2.2. participants patients aged 70 years or older, with unilateral distal radius fracture, no history of upper limb surgery following trauma, no morbidity such as limb paralysis and preoperative deformity, and at least 6 months of follow-up after non-operative or operative treatment were included. cases who had bilateral distal radius fractures, other associated injuries, or open fractures, and patients who did not give consent to participate in our study were excluded. all fractures were classified as b1 and b2 types based on orthopedic trauma association. 2.3. procedure and interventions all fractures underwent an initial closed reduction. all the patients in both groups were radiologically examined three months and six months after the procedure to verify the stability of the reduction and the outcomes. the conservatively treated patients were immobilized with a long cast, and after four weeks, the arm portion of the cast was removed while the forearm part was kept for another 2-4 weeks. then the cast was removed, and patients were advised for functional recovery of the wrist articulation. patients in the surgical group were treated within one week from the traumatic event using different methods like open reduction internal fixation (orif), percutaneous pinning (pcp), and external fixation methods. after the surgery, a splint was applied to the forearm. the immobilization for patients treated with pcp and external fixation was kept for 4-6 weeks and for those in orif group, it was kept for two weeks, followed by rehabilitation. the rehabilitation consisted of physical therapy programs and functional training in self-care and home management. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e62 2.4. outcome assessment all patients’ clinical and functional outcomes were evaluated using three questionnaires at the 3and 6-month follow-ups. also, the range of motion (rom) in injured and contralateral wrists were evaluated and compared between groups at the 3and 6-month follow-ups. the short form 36 (sf36) was used to analyze the quality of life, the disability of the arm shoulder hand (dash) was used to assess wrist function, and a visual analogue scale (vas) was used to evaluate the pain intensity. 2.4.1 short form 36 (sf36) the sf-36 is a general quality of life instrument that measures eight health-related concepts: physical functioning (pf-10 items), role limitations due to physical problems (rp4 items), bodily pain (bp-2 items), general health perceptions (gh-5 items)), vitality (vt-4 items), social functioning (sf-2 items), role limitations due to emotional problems (re-3 items), and perceived mental health (mh-5 items). in addition, a single item that provides an indication of perceived change in general health status over a one-year period (health transition) is also included in the sf-36 .(21) 2.4.2. disability of the arm, shoulder, and hand score (dash) to assess the patient’s functional status during the preceding week, the validated persian version of the disability of the arm, shoulder, and hand score (dash), was used. the questionnaire is designed to evaluate the degree of difficulty in performing several physical activities because of an arm, shoulder or hand problem (21 items), the severity of each of the symptoms of pain, activity-related pain, tingling, weakness and stiffness (5 items), as well as the effects of the condition on social activities, work, and self-image (4 items). the dash also contains two optional four-item modules concerning the ability to work (work module) and to practice sports or play musical instruments (sports/performing arts module) .(22) 2.4.3. visual analogue scale ( vas) the pain visual analogue scale (vas) is a single-item scale, a unidimensional measure of pain intensity. for pain intensity, the scale is most commonly anchored by “no pain” (score of 0) and “pain as bad as it could be” or “unbearable pain” (score of 10). the vas is widely used due to its simplicity and adaptability to a broad range of populations and settings and is broadly accepted as a generic pain measure. 2.4.4. range of motion for range of motion, we measured the amount of wrist flexion and extension as well as radial and ulnar deviation in both fractured and other wrists at 3-month and 6-month follow-ups. the maximum motion of a normal wrist required for daily activities is 60 degrees of extension, 54 degrees of flexion, 40 degrees of ulnar deviation, and 16 degrees of radial deviation, a total of 170 degrees. 2.5. statistical analysis continuous and categorical variables were reported as mean ± standard deviation (sd) and frequency (percentage), respectively. continuous variables were compared between groups using independent samples t-test and categorical variables were compared using chi-squared or fisher exact tests. all statistical analyses were performed using spss version 26 (ibm spss statistics for windows, version xx (ibm corp., armonk, n.y., usa) 3. results 3.1. baseline characteristics a total of 90 patients over 70 years old were included in this study. 45 patients were treated with cast immobilization, and 45 cases were treated using surgical methods. the patients’ mean age at the time of trauma was 77.84 ± 5.90 (range: 7093) years for the surgical group and 77.47 ± 5.4 (range: 7090) years for the conservative group (p = 0.56). the two groups were predominated by women (60% vs. 68%; p = 0.85) and had a similar situation regarding mean dash (84.10 vs. 83.7; p = 0.83), mean pain intensity (7.30 vs. 7.50; p = 0.89), and mean range of motion (68.60 vs. 70.20; p = 0.78) at the time of admission. 3.2. outcomes all patients were evaluated in the 3and 6-month follow-ups. table 1 compares the studied outcomes as well as complications between the groups 3 and 6 months after intervention. except for quality of life in both follow-up times, patients treated with surgical methods showed better outcomes in other aspects, including 3-month (p = 0.042) and 6-month (p = 0.022) mean dash, 3-month (p = 0.013) and 6-month (p = 0.006) mean rom, and 3-month (p = 0.003) and 6-month (p = 0.033) pain intensity based on vas. 3.3. complications a total of 70 (77.77%) adverse events were registered (33 (36.6%) in the casting group and 37 (41.1%) in the surgical group; p = 0.05). in both casting and surgical groups, the most prevalent observed complication was mal-union (25 (27.7%) vs. 10 (11.1%); p = 0.021, respectively), followed by need for reoperation (9 (10%) vs. 8 (8.8%); p = 0.321, respectively). the rate of mal-union (p = 0.021) and superficial radial nerve injury (p = 0.026) were significantly lower in surgical group. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. teimouri et al. 4 table 1: comparing the studied outcomes and complications between the 2 groups 3 and 6 months after intervention outcome surgery group n = 45 casting group n = 45 p-value disability of the arm shoulder hand (dash) 3 months 63.02 ± 9.57 68.29 ± 14.52 0.042 6 months 53.80 ± 9.01 60.04 ± 15.58 0.022 sf-36 3 months 64.20 ± 12.74 62.84 ± 10.31 0.135 6 months 76.87 ± 12.52 70.64 ± 10.92 0.295 pain intensity based on visual analogue scale ( vas) 3 months 3.02 ± 0.98 3.60 ± 1.07 0.009 6 months 1.98 ± 0.86 2.38 ± 0.88 0.033 range of motion (rom) 3 months 129.56 ± 13.00 121.89 ± 15.49 0.013 6 months 146.00 ± 13.67 138.11± 13.11 0.006 complications mal-union 10 (11.1) 25 (27.7) 0.021 surgical site infection 5 (5.5) 0 (0.0) 0.05 superficial radial nerve injury 6 (6.6) 0 (0.0) 0.026 un-union 4 (4.4) 3 (3.3) 0.214 need for reoperation 8 (8.8) 9 (10) 0.321 total 33 (36.6) 37 (41.1) 0.05 data are reported as mean ± standard deviation or frequency (%). at the time of admission, the difference between groups regarding the dash, rom, and pain intensity was not significant. 4. discussion our data showed significant difference between outcomes of drf management in patients who underwent conservative and casting treatments. clinical outcomes in surgical group were better than casting group. we found a significant difference in complications between two groups: malunion and superficial radial nerve injury were significantly lower in surgical group. we considered that a distal radius fracture would affect the whole upper extremity, resulting in a temporary or long-term physical performance impairment (13). this concept applies especially to the elderly population, who are more sensitive to a health-related reduction in quality of life and mobility skills (14). patients who suffer a drf usually experience long-term functional impairments that restrict daily activities (2). distal radius fractures are very common injuries among the elderly, and most drfs that occur in elderly persons are a source of morbidity and loss of quality of life (23). even though drfs are among the most common injuries treated by orthopedic trauma and hand surgeons, the treatment options are vast and the best choice for each case remains debatable variable and remain debatable (6). prevention of this fracture is possible by treating osteoporosis with diet and drugs, including vitamin d, calcium, and bisphosphonate medications. several studies have investigated the functional and radiological outcomes in osteoporotic drf-affected patients; some authors have highlighted that osteoporosis has a negative effect on clinical outcomes in drfs after surgery and suggested that the cause may be the complications related to the low bone mass density of the distal radius, including loss of fixation and late displacement (24). some investigators performing similar studies have stated that there is no significant difference in patient’s overall outcomes between two groups. testa et al. evaluated 91 patients aged 65 years and older with drfs, treated in two groups (cast immobilization versus orif), 1, 3, 6, and 12 months after intervention using similar methods to our study, and they found no significant clinical difference between the casting and the surgical group(25) . arora et al. in a similar study, came to the same conclusion and found no significant difference between 2 treatment methods of drf (26). ju et al. in a meta-analysis of eight studies similar to ours in 2015 compared surgical treatment (440 patient) and cast immobilization (449 patients) and found no significant differences in dash score, vas pain score, grip strength, wrist extension, pronation, supination, or ulnar deviation between the groups. however, they found that the non-surgical group had significantly greater wrist flexion, radial deviation, ulnar variance, and less radial inclination than the surgical group. and they concluded that surgical and non-surgical methods produce similar results in treatment of drfs in the elderly, and minor objective functional differences did not impact subjective function outcome and quality of life . (27) however, the results of our study were similar to the trends observed in some other studies (9, 12, 28), where surgically treated patients tended to achieve better upper extremity function, experience lower pain intensity and greater range this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e62 of motion after treatment, and usually need fewer physical therapy sessions in comparison to casting group to achieve a rather similar function. hung et al. in a study in 2016 concluded that surgical methods resulted in better functional outcomes for drfs in chinese older adults aged 61 to 80 years(29) . after 3-month and 6-month follow-ups, our data showed a significant clinical difference between the casting and the surgical groups, with a better outcome using different surgical methods. this study found a significant improvement in outcomes in the dash, pain score, and range of motion (flexion, extension, and radial deviation) using surgical methods. however, there seemed to be no significant difference between the sf-36 scores of the two groups. this data may suggest that despite the absence of a significant difference in the quality of life between the two groups, the functional outcomes in the mid-term are better in surgically treated patients. thus, the surgical methods are a more admissible option in treating drfs. we found a difference in the incidence of complications: 23.3% in the surgical group and 33.3% in the conservative group. mal-union (38.8% in total) had the highest incidence among registered adverse events in both groups, and approximately 1 out of 3 patients, regardless of the fixation method, were diagnosed with mal-union in follow-ups. regardless of the fixation method, surgical management may result in complications. since the incidence of complications in the surgical group has been lower, it can be concluded that functional outcomes have been better in this group. on the subject of difference between the results of our study and similar investigations done by other authors, we found that in those studies (25-27) they registered more incidence of adverse events in the surgically treated patients in follow-ups (35–45 %) and this may result in worse functional outcome, resulting in the insignificant difference between 2 groups; and as we discussed before, there are many variables that affect both the choice of treatment and outcomes of the chosen treatment, such as the patient’s age, lifestyle, associated medical conditions, compliance, functional demands, limb dominance, type of fracture, severity, alignment of the fracture, condition of the soft tissue, and concomitant fractures. bruce et al. in their study in 2016 point out the absence of a consensus strategy for the treatment of distal radius fractures and the implications of variance in treatment on cost and quality of care, and indicate the need for established, evidence-based guidelines or further clinical trials to assist in the management of this common fracture(30) . the result of our investigation suggests that surgical methods are a more admissible option for the treatment of drfs; however, further prospective randomized controlled studies with larger numbers will be required to evaluate the potential long-term benefits of surgical treatment. this study prospectively investigated the outcome of drfs in iranian elderly patients, and the results followed the trend observed in the general elderly population in other parts of the world (9, 12, 28, 29). 5. limitations selection bias due to lack of randomization and heterogeneous fracture configuration within the group might have limited our results’ power. also, we did not divide fractures into subgroups and we did not separately evaluate the devices used in surgery. 6. conclusion our findings suggest that using surgical methods in treatment of drfs in the elderly seems to be a more admissible option than cast immobilization. the affected limb’s functional outcomes and range of motion were better after surgical treatment compared to cast immobilization treatment. 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions m.gh designed the study, wrote the proposal and initial draft. s.h analyzed the data, gathered data, entered them into spss, and edited the manuscript. m.t introduced the idea, supervised the study, and revised the final draft. 7.3. funding and supports none. 7.4. conflict of interest none. references 1. nellans kw, kowalski e, chung kc. the epidemiology of distal radius fractures. hand clin. 2012;28(2):113-25. 2. jerrhag d, englund m, karlsson mk, rosengren be. epidemiology and time trends of distal forearm fractures in adults a study of 11.2 million person-years in sweden. bmc musculoskelet disord. 2017;18(1):240. 3. earnshaw sa, cawte sa, worley a, hosking dj. colles’ fracture of the wrist as an indicator of underlying osteoporosis in postmenopausal women: a prospective study of bone mineral density and bone turnover rate. osteoporos int. 1998;8(1):53-60. 4. cuddihy mt, gabriel se, crowson cs, o’fallon wm, melton lj, 3rd. forearm fractures as predictors of subsequent osteoporotic fractures. osteoporos int. 1999;9(6):469-75. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. teimouri et al. 6 5. nordvall h, glanberg-persson g, lysholm j. are distal radius fractures due to fragility or to falls? a consecutive case-control study of bone mineral density, tendency to fall, risk factors for osteoporosis, and health-related quality of life. acta orthop. 2007;78(2):271-7. 6. jariwala ac, phillips ar, storey pa, nuttall d, watts ac. internal fixation versus other surgical methods for treating distal radius fractures in adults. cochrane database syst rev. 2018;2018(7):cd011212. 7. hammert wc, kramer rc, graham b, keith mw. aaos appropriate use criteria: treatment of distal radius fractures. j am acad orthop surg. 2013;21(8):506-9. 8. bartl c, stengel d, bruckner t, gebhard f. the treatment of displaced intra-articular distal radius fractures in elderly patients. dtsch arztebl int. 2014;111(46):779-87. 9. wong tc, chiu y, tsang wl, leung wy, yam sk, yeung sh. casting versus percutaneous pinning for extraarticular fractures of the distal radius in an elderly chinese population: a prospective randomised controlled trial. j hand surg eur vol. 2010;35(3):202-8. 10. handoll hh, madhok r. conservative interventions for treating distal radial fractures in adults. cochrane database syst rev. 2003(2):cd000314. 11. mulders mam, van eerten pv, goslings jc, schep nwl. non-operative treatment of displaced distal radius fractures leads to acceptable functional outcomes, however at the expense of 40% subsequent surgeries. orthop traumatol surg res. 2017;103(6):905-9. 12. rhee pc, shin ay. management of complex distal radius fractures: review of treatment principles and select surgical techniques. j hand surg asian pac vol. 2016;21(2):140-54. 13. toon dh, premchand rax, sim j, vaikunthan r. outcomes and financial implications of intra-articular distal radius fractures: a comparative study of open reduction internal fixation (orif) with volar locking plates versus nonoperative management. j orthop traumatol. 2017;18(3):229-34. 14. levin ls, rozell jc, pulos n. distal radius fractures in the elderly. j am acad orthop surg. 2017;25(3):179-87. 15. handoll hh, madhok r. closed reduction methods for treating distal radial fractures in adults. cochrane database syst rev. 2003;2003(1):cd003763. 16. martineau pa, berry gk, harvey ej. plating for distal radius fractures. orthop clin north am. 2007;38(2):193201, vi. 17. egol ka, walsh m, romo-cardoso s, dorsky s, paksima n. distal radial fractures in the elderly: operative compared with nonoperative treatment. j bone joint surg am. 2010;92(9):1851-7. 18. jupiter jb, marent-huber m. operative management of distal radial fractures with 2.4-millimeter locking plates: a multicenter prospective case series: surgical technique. jbjs. 2010;92(supplement_1_part_1):96-106. 19. arora r, lutz m, deml c, krappinger d, haug l, gabl m. a prospective randomized trial comparing nonoperative treatment with volar locking plate fixation for displaced and unstable distal radial fractures in patients sixty-five years of age and older. j bone joint surg am. 2011;93(23):2146-53. 20. orbay jl, fernandez dl. volar fixed-angle plate fixation for unstable distal radius fractures in the elderly patient. j hand surg am. 2004;29(1):96-102. 21. montazeri a, goshtasebi a, vahdaninia m, gandek b. the short form health survey (sf-36): translation and validation study of the iranian version. qual life res. 2005;14(3):875-82. 22. mousavi sj, parnianpour m, abedi m, askary-ashtiani a, karimi a, khorsandi a, et al. cultural adaptation and validation of the persian version of the disabilities of the arm, shoulder and hand (dash) outcome measure. clin rehabil. 2008;22(8):749-57. 23. vogt mt, cauley ja, tomaino mm, stone k, williams jr, herndon jh. distal radius fractures in older women: a 10-year follow-up study of descriptive characteristics and risk factors. the study of osteoporotic fractures. j am geriatr soc. 2002;50(1):97-103. 24. ostergaard pj, hall mj, rozental td. considerations in the treatment of osteoporotic distal radius fractures in elderly patients. curr rev musculoskelet med. 2019;12(1):50-6. 25. testa g, vescio a, di masi p, bruno g, sessa g, pavone v. comparison between surgical and conservative treatment for distal radius fractures in patients over 65 years. j funct morphol kinesiol. 2019;4(2):26. 26. arora r, gabl m, gschwentner m, deml c, krappinger d, lutz m. a comparative study of clinical and radiologic outcomes of unstable colles type distal radius fractures in patients older than 70 years: nonoperative treatment versus volar locking plating. j orthop trauma. 2009;23(4):237-42. 27. ju jh, jin gz, li gx, hu hy, hou rx. comparison of treatment outcomes between nonsurgical and surgical treatment of distal radius fracture in elderly: a systematic review and meta-analysis. langenbecks arch surg. 2015;400(7):767-79. 28. chan yh, foo tl, yeo cj, chew wy. comparison between cast immobilization versus volar locking plate fixation of distal radius fractures in active elderly patients, the asian perspective. hand surg. 2014;19(1):19-23. 29. hung lp, leung yf, ip wy, lee yl. is locking plate fixation a better option than casting for distal radius fracture in elderly people? hong kong med j. 2015;21(5):407-10. 30. bruce kk, merenstein dj, narvaez mv, neufeld sk, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e62 paulus mj, tan tp, et al. lack of agreement on distal radius fracture treatment. j am board fam med. 2016;29(2):218-25. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e32 or i g i n a l re s e a rc h ottawa risk scale in predicting the outcome of chorionic obstructive pulmonary disease exacerbation in emergency department; a diagnostic accuracy study mostafa alavi-moghaddam1, hossein partovinezhad2, shayan dasdar3, maryam farjad1∗ 1. emergency department, imam hossein hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, zanjan university of medical sciences, zanjan, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: january 2023; accepted: february 2023; published online: 9 april 2023 abstract: introduction: the disposition decision is a great challenge for clinicians in managing patients with chronic obstructive pulmonary disease (copd) exacerbation. this study aimed to evaluate the accuracy of ottawa copd risk scale (ocrs) in predicting the short-term adverse events in the mentioned patients. methods: this prospective diagnostic accuracy study was conducted on copd exacerbation cases who were referred to the emergency department (ed). patients were followed up for 30 consecutive days for adverse events including the need for intubation, non-invasive ventilation, myocardial infarction, readmission, and death from any cause, and finally the accuracy of ocrs in predicting the outcome was evaluated. results: 362 patients with the mean age of 65.55 ± 10.65 (695) years were evaluated (58.0% male). among the patients, 164 (45.3%) cases were discharged from ed, and 198 (54.7%) were admitted to the hospital. 136 (37.6%) cases experienced at least one of the studied short-term adverse events. the mean ocsd score of this series was 1.96 ± 2.39 (0 – 10). the area under the curve of ocrs in predicting the outcome of copd patients was 0.814 (95%ci: 0.766 – 0.862). the best cut-off point of the scale in predicting the outcome was 1.5. the sensitivity and specificity of the scale were 75.75% (95%ci: 69.6% – 81.42%) and 89.63% (95%ci: 83.67% – 93.66%), respectively. by employing this threshold, 48 (13.25%) cases would have unnecessary hospitalization, and 17 (0.04%) would be discharged incorrectly. conclusion: the ocrs has acceptable level of prediction accuracy in predicting the short-term adverse event of copd patients. the use of this scoring in the routine practice of ed clinicians can lead to a reduction in unnecessary admissions and unsafe discharge for these patients. keywords: pulmonary disease, chronic obstructive; risk assessment; patient outcome assessment; sensitivity and specificity; clinical decision rules cite this article as: alavi-moghaddam m, partovinezhad h, dasdar s, farjad m. ottawa risk scale in predicting the outcome of chorionic obstructive pulmonary disease exacerbation in emergency department; a diagnostic accuracy study. arch acad emerg med. 2023; 11(1): e32. https://doi.org/10.22037/aaem.v11i1.2023. 1. introduction chronic obstructive pulmonary disease (copd) is a serious and frequent respiratory condition ranking as the third cause of disability-adjusted life-years among old aged people according to the latest global burden of disease (1). each year, more than 3 million people die from copd around the world (2). this respiratory disorder, mostly caused by smoking, is characterized by progressive and poorly reversible airway ob∗corresponding author: maryam farjad; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989123178240, email: farjad.mary@gmail.com, orcid: https://orcid.org/0000-0002-1000-6495. struction due to chronic inflammation (3). exacerbation of copd is defined as an acute deterioration in the usual stable course of the disease. this condition could lead to many emergency department (ed) visits (4). patients with copd exacerbation could sufficiently benefit from treatments in the ed to be discharged after a few hours with no risk. however, a small number of the patients might experience critical short-term adverse events, necessitating hospital admission and aggressive management to ensure a safe outcome (5). it is not reasonable to admit all patients with copd exacerbation, as many hospitals have a shortage of beds and staff. on the other hand, unnecessary hospital admission could bear undesirable health and financial consequences. therefore, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. alavi-moghaddam et al. 2 the disposition decision is a great challenge for clinicians in managing patients with copd exacerbation (6). a valid set of criteria in deciding whether to continue treatment in the ed, admit, or discharge the patients would be cost-effective and safe. therefore, the scores and tools that have been developed to predict the outcomes of copd exacerbation are very helpful. the ottawa copd risk scale (ocrs) is a tool designed to predict outcomes of copd exacerbation. the primary purpose of this scale is to assist physicians in deciding whether to admit copd patients or discharge them with no need for complex and expensive diagnostic tests (7). utilizing the ocrs in the disposition decision of patients with copd exacerbation in ed can remarkably reduce unnecessary hospitalizations and unsafe discharges (8). to date, few studies have assessed the validity of ocrs prospectively. therefore, we aimed to evaluate the accuracy of the ocrs in predicting short-term adverse events of the patients with copd exacerbation, referred to the ed. 2. methods 2.1. study design and setting this prospective diagnostic accuracy study was conducted at imam hossein and shohadaye tajrish hospitals in tehran, iran, affiliated with shahid beheshti university of medical sciences, from january 2021 to december 2022. all patients were informed about the study’s purpose and procedures, and written informed consents were obtained. the study protocol was in accordance with the declaration of helsinki. the institutional review board of shahid beheshti university of medical sciences reviewed and approved this study (ethics code: ir.sbmu.msp.rec.1398.271). 2.2. study population all patients with copd exacerbation who attended the ed were studied. the inclusion criteria were 1) admission with copd exacerbation, defined as increase in at least two of the following symptoms two symptoms of breathlessness, sputum volume and sputum purulence; 2) previous copd diagnosis or a history of at least one year of chronic dyspnea or cough with sputum; 3) a history of at least 15 pack-years of smoking with moderate to severe airflow obstruction; 4) age 50 years or older. the extremely ill patients who, after 2 to 12 hours of management in ed, had a saturation of oxygen <85%, heart rate >130 beats/min, systolic blood pressure < 85mmhg, confusion, long-term hemodialysis, chest pain indicating heart attack requiring treatment, or st–t interval changes indicating ischemia were excluded. the inclusion and exclusion criteria were selected upon the original study of the ocrs by stiell et al. (8). table 1: baseline characteristics of the studied cases variable value gender male 210 (58.0) female 152 (42.0) age (year) mean ± sd 65.55 ± 10.65 triage level (esi) 1 44 (12.2) 2 51 (14.1) 3 267 (73.8) medical history hypertension 210 (59.2) diabetes mellitus 65 (18.3) heart failure 41 (11.5) chronic renal failure 6 (1.7) stroke 23 (6.2) cancer 11 (3.1) surgical history coronary artery bypass graft 23 (6.4) percutaneous coronary intervention 7 (1.9) peripheral vascular intervention 64 (17.7) history of intubation yes 11 (3.0) no 351 (97.0) vital signs on arrival hear rate (/minute) 94.85 ± 18.89 respiratory rate (/minute) 9.61 ± 4.13 temperature (celsius) 36.90 ± 3.08 o2 saturation (%) 86.75 ± 6.73 ecg on arrival atrial filtration 34 (9.4) right axis deviation 110 (30.4) atrioventricular block 54 (14.9) right bundle branch block 81 (22.4) sinus tachycardia 104 (28.7) chest x-ray findings pneumonia 109 (30.1) plural effusion 98 (27.1) cardiomegaly 140 (38.7) o2 therapy in emergency department venturi mask 187 (51.7) non-rebreathing mask 141 (39.0) non-invasive ventilation 17 (4.7) data are presented as mean ± standard deviation (sd) or frequency (%). esi: emergency severity index; ecg: electrocardiography. 2.3. data gathering a general practitioner was responsible for data gathering under the direct supervision of an emergency physician specialist. the following data were collected from the enrolled patients: gender, age, triage level, medical and surgical history, previous intubation, arrival vital signs (blood pressure, heart rate, respiratory rate, temperature, oxygen saturation), electrocardiography (ecg) on arrival, findings of the chest x-ray, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e32 table 2: screening performance characteristics of the ottawa risk scale in predicting the outcome of patients with chronic obstructive pulmonary disease (copd) characteristics value (95%ci) sensitivity 75.75% (69.6% – 81.42%) specificity 89.63% (83.67% – 93.66%) positive predictive value 89.82% (83.95% – 93.78%) negative predictive value 75.38% (68.61% – 81.13%) positive likelihood ratio 8.82 (5.60 – 13.88) negative likelihood ratio 0.32 (0.25 – 0.41) total accuracy 86.5% (82.7% – 90.3%) ci: confidence interval. and o2 therapy in the ed. the ocrs score was calculated for all the patients in a 3-stage review system. 1) initial assessment step: history of coronary artery bypass graft (cabg), history of intervention for peripheral vascular disease, history of intubation for respiratory distress, and arrival heart rate >110 beats/min. 2) investigations step: acute ischemic changes in arrival ecg, evidence of pulmonary congestion on chest x-ray, hemoglobin <100 g/l, urea >12 mmol/l, serum co2 >35 mmol/l. 3) reassessment after treatment step: oxygen saturation <90% on room air or usual o2, heart rate >120 beats/min. each of the mentioned criteria, is allocated a score between 1-3, resulting in a total score between 0-16. 2.4. outcomes patients were followed up for 30 consecutive days for shortterm adverse events including the need for intubation, noninvasive ventilation, myocardial infarction, readmission, and death from any cause. 2.5. statistical analysis data were analyzed using spss software version 26. the findings were reported as mean ± standard deviation or frequency (%). the best cut-off point for the scale in predicting the outcome of copd patients was calculated using the area under the receiver operating characteristics curve (auc). the screening performance characteristics of the scale (sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios) were calculated using the vassarstats calculator and reported with a 95% confidence interval. 3. results 3.1. baseline characteristics of studied cases in this study, 362 patients that met the inclusion and exclusion criteria were enrolled. the mean age of the patients was 65.55 ± 10.65 (695) years, consisting of 58.0% male cases. the baseline characteristics of the patients are depicted in table 1. among them, 267 (73.8%) were in level 3 emergency severity index (esi) triage. the most frequent underlying comorbidities in this series were hypertension (59.2%), diabetes mellitus (18.3%), and heart failure (11.5%). history of the patients revealed that 23 (6.4%) patients had cabg, 64 patients (17.7%) had an intervention for peripheral vascular disease, and 11 patients (3.1%) had intubation for respiratory distress. right axis deviation (30.4%) and cardiomegaly (38.7%) were the most frequent ecg and chest x-ray findings, respectively. 3.2. outcomes among the patients, 164 (45.3%) cases were discharged from ed, and 198 (54.7%) were admitted to the hospital. in this series of patients, 136 (37.6%) cases experienced at least one of studied short-term adverse events (48 (13.3%) cases needed non-invasive ventilation, 31 (8.6%) cases were readmitted after ed discharge, 26 (7.2%) cases needed intubation, 20 (5.5%) cases experienced myocardial infarction, 6 (1.7) cases died within 30 days after discharge, 5 (1.4%) died after admission). 3.3. screening performance characteristics of ocrs the mean ocsd score of this series was 1.96 ± 2.39 (0 – 10). figure 1 shows the frequency distribution of the ocsd score. the area under the curve of ocrs in predicting the outcome of copd patients was 0.814 (95%ci: 0.766 – 0.862). the best cut-off point of the scale in predicting the outcome was 1.5. table 2 summarizes the screening performance characteristics of ocrs. the sensitivity and specificity of the scale were 75.75% (95%ci: 69.6% – 81.42%) and 89.63% (95%ci: 83.67% – 93.66%), respectively. by employing this threshold in the present study, 48 (13.25%) of the patients would have unnecessary hospitalization, and 17 (0.04%) would be discharged incorrectly. 4. discussion in this study, the ocrs scale was used to predict the shortterm adverse events of copd exacerbation in patients presenting to ed, and it was found that the auc value was greater than 0.8, indicating a high level of prediction accuracy. herein, the best cut-off value was detected as ocrs greater than 1, with the sensitivity and specificity of 75.75% and 89.63%, respectively. the present study’s short-term adverse events rate was estimated as 38.01%. in the original study of ocrs validation, 9.5% of the patients had experienced short-term adverse events (8). this rate in similar studies utilizing the ocrs scale was reported as 74% and 20.7%, both from turkey this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. alavi-moghaddam et al. 4 figure 1: frequency distribution of the ottawa chronic obstructive pulmonary disease risk scale (ocrs) score in the studied population. figure 2: the area under the receiver operating characteristic (roc) curve (auc) of the ottawa risk scale in predicting the outcome of patients with chronic obstructive pulmonary disease (auc= 0.814 (95%ci: 0.766 – 0.862)). (9, 10). this wide range in the rate of short-term adverse events from different centers could be due to the variation in the patients’ clinical condition, the level of facilities, and management strategies. however, the important point that has been consistently emphasized in these studies is a considerable number of short-term adverse events in the patients discharged from the ed. this shows that an accurate and precise criterion for an error-free disposition decision is of great importance. several tools have been introduced to help predict copd exacerbation outcomes. bode (body mass index, airflow obstruction, dyspnea, and exercise capacity) is one of the most widely used indices for predicting disease severity and mortality. this index derived from an international collaboration in 2004 aimed at finding the risk factors of death in patients with copd. the validation was performed on 625 patients, yielding an auc of 0.74 (11). a study from france established “score 2008” based on age, grade of dyspnea at steady state, and number of clinical signs of severity. the clinical accuracy was assessed on 1824 patients with copd admitted to the ed. accordingly, they reported an auc of 0.83 for score 2008 to predict in-hospital mortality in copd patients (12). in another study from the united kingdom in 2012, the clinical admission data of 920 patients were investigated for the predictors of mortality in copd patients. they reported that high dyspnoea, eosinopenia, consolidation acidaemia, and atrial fibrillation (decaf) score is a strong predictor of mortality with an auc of 0.86 (13). while these multicomponent indices could successfully predict long-term mortality, they were not designed for other short-term adverse events. ocrs was designed to estimate the probability of short-term adverse events in patients with copd exacerbation. in this study, we measured the auc for oscd and it was equal to 0.81, consistent with the previous reports (9, 10). similar to the original oscd study, the best cut-off value was above 1, with the sensitivity and specificity of 75.75% and 89.63%, respectively. by employing this threshold in the present study, 48 (13.25%) of the patients would have unnecessary hospitalization, and 17 (0.04%) would be discharged incorrectly. therefore, ocrs is a useful tool to predict the outcome of copd exacerbation and ed physicians have approved and supported its applicability and effectiveness in ed. it should be noted that whether a patient is admitted or discharged from ed is not merely related to disease severity. many non-medical factors can alter this decision, including hospital crowdedness, access to equipped ed, home care support, and patients’ preferences. however, ocrs can help ed clinicians to gauge their disposition decision according to their local practice. in a study on the applicability of the ocrs, 70.2% of the ed physicians confirmed and supported the effectiveness of ocrs to be used in ed for patients with copd exacerbation (14). 5. limitations the findings of this study should be viewed in the context of several limitations. first, this study has a small population. studies with a larger statistical population are recommended to confirm and expand the findings of this study. it should also be noted that several of short-term adverse events were recorded to assess the performance of ocrs in predicting copd outcomes. moreover, the patients were not analyzed in a matched manner regarding the underlying diseases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e32 6. conclusion the results of this study revealed the clinical validity of ocrs in predicting short-term adverse event in copd patients presenting to the ed. the use of this scoring in the routine practice of ed clinicians can lead to a reduction in unnecessary admissions and unsafe discharge of patients with copd exacerbation. 7. declarations 7.1. acknowledgments hereby, the staff of medical records department and treatment staff of imam hossein and shohadaye tajrish hospitals are thanked for their cooperation in data gathering for this project. 7.2. conflict of interest there is no conflict of interest to declare. 7.3. fundings and supports none. 7.4. authors’ contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. references 1. vos t ls, abbafati c, abbas km, abbasi m, abbasifard m, abbasi-kangevari m, et al. global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. lancet (london, england). 2020;396(10258):1204-22. 2. rabe kf, watz h. chronic obstructive pulmonary disease. lancet (london, england). 2017;389(10082):1931-40. 3. barnes pj, burney pg, silverman ek, celli br, vestbo j, wedzicha ja, et al. chronic obstructive pulmonary disease. nature reviews disease primers. 2015;1:15076. 4. zafar ma, loftus tm, palmer jp, phillips m, ko j, ward sr, et al. copd care bundle in emergency department observation unit reduces emergency department revisits. respiratory care. 2020;65(1):1-10. 5. kim s, emerman cl, cydulka rk, rowe bh, clark s, camargo ca. prospective multicenter study of relapse following emergency department treatment of copd exacerbation. chest. 2004;125(2):473-81. 6. rowe bh, villa-roel c, guttman a, ross s, mackey d, sivilotti ml, et al. predictors of hospital admission for chronic obstructive pulmonary disease exacerbations in canadian emergency departments. academic emergency medicine : official journal of the society for academic emergency medicine. 2009;16(4):316-24. 7. stiell ig, clement cm, aaron sd, rowe bh, perry jj, brison rj, et al. clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study. cmaj : canadian medical association journal = journal de l’association medicale canadienne. 2014;186(6):e193204. 8. stiell ig, perry jj, clement cm, brison rj, rowe bh, aaron sd, et al. clinical validation of a risk scale for serious outcomes among patients with chronic obstructive pulmonary disease managed in the emergency department. cmaj : canadian medical association journal = journal de l’association medicale canadienne. 2018;190(48):e1406-e13. 9. kocak ao, cakir z, akbas i, gur sta, kose mz, can no, et al. comparison of two scores of short term serious outcome in copd patients. the american journal of emergency medicine. 2020;38(6):1086-91. 10. unal a, bayram b, ergan b, can k, ergun yk, kilinc o. comparison of two scores for short-term outcomes in patients with copd exacerbation in the emergency department: the ottawa copd risk scale and the decaf score. erj open res. 2023;9(2):00436-2022. 11. celli br, cote cg, marin jm, casanova c, montes de oca m, mendez ra, et al. the body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. the new england journal of medicine. 2004;350(10):1005-12. 12. roche n, zureik m, soussan d, neukirch f, perrotin d. predictors of outcomes in copd exacerbation cases presenting to the emergency department. the european respiratory journal. 2008;32(4):953-61. 13. steer j, gibson j, bourke sc. the decaf score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. thorax. 2012;67(11):970-6. 14. hale mk, stiell ig, clement cm. emergency department management of heart failure and copd: a national survey of attitudes and practice. cjem. 2016;18(6):429-36. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e69 or i g i n a l re s e a rc h risk factors of recurrent anal abscess in patients with type 2 diabetes mellitus; a 4-year retrospective study nasser malekpour alamdari1, siamak afaghi2, farzad esmaeili tarki2, mohammad fathi3, sara besharat4, fatemehsadat rahimi1∗ 1. clinical research and development center, department of surgery, shahid modarres hospital, shahid beheshti university of medical sciences, tehran, iran. 2. research institute of internal medicine, shahid modarres hospital, shahid beheshti university of medical sciences, tehran, iran. 3. critical care quality improvement research center, shahid modarres hospital, shahid beheshti university of medical sciences, tehran, iran. 4. department of radiology, shahid labbafinezhad hospital, shahid beheshti university of medical sciences, tehran, iran. received: june 2022; accepted: july 2022; published online: 24 august 2022 abstract: introduction: anal abscess is considered as a relatively common compilation in type 2 diabetes mellitus (t2dm) patients. this study aimed to determine the risk factors of recurrent anal abscess in t2dm patients. methods: in this 4-year retrospective cross-sectional study, t2dm patients hospitalized due to anal abscess in shahid modarres hospital, tehran, iran from december 2016 to december 2020 were studied. the independent risk factors of disease recurrence were determined among demographic factors, underlying diseases, diabetes-related factors, clinical factors, laboratory parameters, abscess type, and culture using multivariate stepwise logistic regression analysis. results: 203 patients were enrolled in the study. 58 (28.6%) patients had at least one re-occurrence of anal abscess during four years. the recurrent episodes had occurred more frequently in the first year after the initial treatment (55.2%). the prevalence of comorbidities such as metabolic syndrome, coronary artery disease, chronic kidney disease, end stage renal disease, and peripheral vascular disease was significantly higher amongst patients with abscess recurrence. the patients with recurrent anal abscess had statically significant poor glycemic control (hba1c > 7.5), decreased levels of estimated glomerular filtration rate (e-gfr), and higher c-reactive protein (crp) upon the first admission. presence of metabolic syndrome, hba1c > 7.5%, wbc > 11.0 ×109/l, and crp > 5 mg/l were amongst the independent risk factors of recurrence. hba1c > 7.5% was the greatest independent risk factor of anal abscess recurrence (or=2.68, 95% ci: 1.37-5.25; p < 0.001). the area under the receiver operating characteristic (roc) curve (auc) of hba1c, crp, and wbc in predicting the risk of abscess recurrence was 0.81, 0.71, and 0.64, respectively. conclusion: th recurrence rate of anal abscess in this series was 28.6 %. it seems that in t2dm patients with uncontrolled diabetes who have metabolic syndrome and increased crp and wbc in their routine tests, the probability of anal abscess reoccurrence is high. keywords: diabetes mellitus; abscess; metabolic syndrome; leukocytosis; diabetes complications cite this article as: malekpour alamdari n, afaghi s, esmaeili tarki f, fathi m, besharat s, rahimi f. risk factors of recurrent anal abscess in patients with type 2 diabetes mellitus; a 4-year retrospective study. arch acad emerg med. 2022; 10(1): e69. https://doi.org/10.22037/aaem.v10i1.1692. 1. introduction anal abscess is among the most prevalent anorectal diseases, and it is more frequent amongst the youth in their fourth ∗corresponding author: fatemehsadat rahimi; clinical research and development center, department of surgery, shahid modarres hospital, shahid beheshti university of medical sciences, tehran, iran. tel: +989128303107, email: t.rahimi@sbmu.ac.ir, orcid: https://orcid.org/0000-0001-8463-6214. decade of life (1). its incidence rate is 16-20 per 100,000 with a 15% risk of future fistula development (2). surgical therapy aids in decompression and pain alleviation of the abscess, as well as in prevention of the development of fournier’s gangrene or pelvic sepsis (3); whilst, treatment with antibiotics alone is regarded as ineffective, resulting in therapeutic failure, illness relapse, and the creation of a fistula (4). some patients only experience a single episode of the illness, while other patients have recurring instances. it has been estabthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. malekpour alamdari et al. 2 lished that diabetes mellitus (dm) is related to occurrence of anal abscess (5). also, the prevalence of anal abscess is recognized to be significantly more in cases afflicted with type 2 diabetes mellitus (t2dm), than those with type 1 diabetes mellitus (t1dm), indicating the fact that insulin resistance and metabolic syndrome associated with obesity and lifestyle is more important than autoimmune factors. it’s probable that, like several other diabetes sequelae, anal abscess is related to lower glycemic control and hyperglycemia, although the link isn’t apparent (5). recurring anal abscess can last for months or years, and it’s linked to a decline in the patient’s condition and a decrease in their quality of life (6). moreover, these repeated anal abscesses raise the health-care system’s long-term expenses. whilst some of the risk factors for occurrence of anal abscess, including high daily salt intake, active smoking, alcohol use, obesity, and dm have been recognized, there is presently a scarcity of information about which patient-related characteristics are most prognostic of anal abscess recurrence (6-8). moreover, determining the risk factors might also aid one to further comprehend the pathogenesis of anal abscess. hence, the initial goal of our study has been to evaluate the risk factors for recurrence of anal abscess among t2dm patients with treated initial anal abscess. 2. methods 2.1. study design and setting this retrospective single-center cross-sectional study was conducted on medical records of t2dm patients hospitalized with the diagnosis of anal abscess in shahid modarres hospital, tehran, iran, from december 2016 to december 2020. shahid modarres hospital is a tertiary and referral center of general surgery in the west of tehran, conducting special clinical visit programs for the management and followup of t2dm patients under consideration of both general surgeons and internal medicine specialist teams. the study protocol was reviewed and approved by ethics committee of shahid beheshti university of medical sciences (ethical number: ir.sbmu.msp.rec.1398.956). all the patients who participated in this study, have provided a letter of consent to cooperate in this essay. 2.2. participants all adult t2dm patients with diagnosis of anal abscess during the study period were enrolled using census sampling method. meeting one of the following criteria was considered as verification of diabetes mellitus during the initial admission: 1. a level of fasting plasma glucose (fpg) exceeding 126 mg/dl (7.0 mm/l), or 2. hb a1c greater than 6.5%. anal abscess was defined based on international classification of diseases, eleventh revision (icd-11)(9). individuals infected with human immunodeficiency virus (hiv ) or afflicted with other immune-compromising conditions, including those with more than 2 mg/kg steroid drug intake/day, gastrointestinal malignancies, and crohn’s disease, and those who were expired during the first hospitalization or had incomplete medical documentation were excluded. all the patients received surgical treatment of incision and drainage with or without fistulotomy/ fistulectomy and antibiotic therapy as appropriate. 2.3. data gathering potential risk factors of anal abscess recurrence were divided into 7 categories: 1. demographic factors: age, gender, history of smoking and alcohol consumption, 2. underlying diseases: metabolic syndrome, hypertension, dyslipidemia, end stage renal disease (esrd), coronary artery disease (cad), chronic kidney disease (ckd), and peripheral vascular disease, 3. diabetes-related factors: diabetes duration, hemoglobin a1c (hba1c) levels, and diabetic foot ulcer, 4. clinical status: presence of fever, length of hospitalization, and surgical site infection 5. laboratorial findings: white blood cell count (wbc), estimated glomerular filtration rate (e-gfr), c-reactive protein (crp), creatinine, and albumin, 6. types of anal abscess: perianal, ischiorectal, inter-sphincteric, supralevator, as well as fistula formation, and 7. microbiology based on abscess culture results. all data were gathered based on patients’ electronic medical documents, extracted by two skilled medical researchers, and were double-checked before being entered into analysis. 2.4. statistical analysis spss version 25.0 (spss, chicago, il, usa) or r software version 3.6.3 were employed to carry out the statistical analysis. data were analyzed using the shapiro-wilk test to confirm their normal distribution. categorial and continuous variables were presented as case number (percentage) and mean ± standard deviation, respectively. to compare the categorical variables, chi-squared or fisher’s exact test was utilized as appropriate. independent t-test, or mann–whitney u test was used for comparison of means between continuous variables as necessitated. the mentioned potential risk factors for anal abscess have been assessed utilizing multivariate logistic regression test and indicated as odds ratio (or) and 95% confidence interval. moreover, the receiver operating characteristic (roc) curves were drawn to find the predictive values of hba1c, crp, and wbc levels regarding anal abscess relapse. two-sided p-value of less than 0.05 has been deemed statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e69 table 1: comparing the demographic, clinical, and laboratory parameters of diabetic patients with and without recurrent anal abscess characteristics recurrent anal abscess p yes (n = 58) no (n = 145) demographic age (year) 45.9 ± 7.8 48.1 ± 8.3 0.08 gender (male) 43 (74.1) 105 (72.4) 0.80 active smoking (yes) 19 (32.7) 37 (25.5) 0.29 smoking pack-year 11.3 ± 5 .7 9.9 ± 4.7 0.07 alcohol consumption 7 (12.1) 19 (13.1) 0.84 comorbidities metabolic syndrome 22 (37.9) 25 (17.2) 0.001 hypertension 46 (79.3) 127 (87.6) 0.13 dyslipidemia 32 (55.2) 102 (70.3) 0.06 coronary artery disease 34 (58.6) 53 (36.5) 0.001 chronic kidney disease 29 (50) 48 (33.1) 0.02 end stage renal disease 10 (17.2) 9 (6.2) 0.01 peripheral vascular disease 10 (17.2) 11 (7.6) 0.04 diabetes-related factors diabetes duration 13.0 ± 4.6 11.9 ± 6.1 0.21 hba1c 6.0 ± 1.4 5.8 ± 1.5 0.38 poor glycemic control (hba1c>7.5) 42 (72.4) 61 (42.1) 0.001 diabetic foot ulcer 7 (14.6) 9 (6.2) 0.16 clinical fever 53 (91.4) 136 (93.8) 0.54 length of hospital stay (days) 12.3 ± 2.7 11.2 ± 6.6 0.22 surgical site infection 3 (5.2) 9 (6.2) 0.77 laboratory findings white blood cell (/mm3 ) 15.5 ± 7.9 13.1 ± 6.1 0.02 c-reactive protein (mg/dl) 7.9 ± 3.1 6.7 ± 3.5 0.02 e*glomerular filtration rate (ml/min) 88.3 ± 6.3 91.9 ± 10.7 0.02 creatinine (mg/dl) 1.2 ± 1.3 1.0 ± 1.2 0.29 albumin (g/l) 3.7 ± 1.6 4.0 ± 1.8 0.27 data are presented as mean ± standard deviation or frequency (%). hb: hemoglobin; *: estimated. table 2: comparing the abscess characteristics of diabetic patients with and without recurrent anal abscess characteristics recurrent anal abscess p yes (n = 58) no (n = 145) anal abscess type perianal 34 (58.6) 91 (62.7) 0.58 ischiorectal 13 (22.4) 24 (16.5) 0.32 inter-sphincteric 5 (8.6) 21 (14.5) 0.26 supralevator 6 (10.3) 9 (6.2) 0.30 formation of fistula 19 (32.7) 39 (26.9) 0.40 culture gram-positive and gram-negative aerobic bacteria 7 (12.1) 13 (8.9) 0.50 gram-positive aerobic bacteria only 9 (15.5) 25 (17.2) 0.46 gram-negative aerobic bacteria only 6 (10.3) 11 (7.6) 0.52 anaerobic bacteria only 2 (3.4) 4 (2.7) 0.79 mixed aerobic and anaerobic flora 25 (43.1) 50 (34.5) 0.25 no culture result 9 (15.5) 42 (28.9) 0.07 data are presented as frequency (%). 3. results 3.1. baseline characteristics of studied cases a total of 252 cases, diagnosed with anal abscess based on icd-11 definition, were evaluated. 49 cases were excluded and finally, 203 patients with t2dm who were hospitalized with the diagnosis of anal abscess for the first time were enrolled in the study (figure 1). the perianal type was the most this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. malekpour alamdari et al. 4 table 3: multivariate stepwise logistic regression analysis for independent risk factors of recurrent anal abscess in type 2 diabetes mellitus patients factor unit/level or 95% ci p-value hba1c > 7.5% 2.68 1.37-5.25 0.00 creactive protein > 5 mg/l 2.04 1.05-3.94 0.01 white blood cells >11.0 ×109 /l 1.35 1.15-1.58 0.01 metabolic syndrome presence vs absence 1.99 1.02-3.85 0.04 hb: hemoglobin; or: odds ratio; ci: confidence interval. common form of abscess. 58 (28.6%) patients had at least one re-occurrence of anal abscess in the following four years after initial treatment. the recurrence episodes had more frequently occurred during the first year after the initial treatment (55.2%) compared to second year (18.9%), third year (15.5%), and fourth year (10.3%) (figure 2). fistula formation was observed in 32.7% and 26.9% of patients with and without recurrence, respectively (p = 0.4). 3.2. risk factors of recurrence tables 1 and 2 compare the demographic, clinical, and laboratory parameters as well as abscess characteristics of diabetic patients with and without recurrent anal abscess. the mean age of patients with and without recurrence was 45.9 ± 7.8 and 48.1 ± 8.3 years, respectively (p = 0.08). also, both groups had similar sociodemographic characteristics in terms of male gender predominancy (47.1% vs. 72.4%, p = 0.80), smoking (32.7% vs. 25.5%, p = 0.29), severity of smoking (11.3 ± 5 .7 vs 9.9 ± 4.7 packyear, p = 0.07), and alcohol consumption (12.1% vs 13.1%, p = 0.07). the prevalence of metabolic syndrome, coronary artery disease, chronic kidney disease, end stage renal disease, and peripheral vascular disease comorbidities were significantly higher amongst patients with abscess re-occurrence. the patients with recurrent anal abscess had statically significant poor glycemic control (hba1c > 7.5), decreased levels of estimated glomerular filtration rate (e-gfr), and higher c-reactive protein (crp) upon the first admission. on microbiological evaluation, the mixed aerobic and anerobic bacteria flora was the most prevalent culture result (p = 0.25). based on the multivariate step-by-step logistic regression analysis on all potential predictors of perianal abscess recurrence (table 3), it was found that the independent risk factors were: presence of metabolic syndrome, hba1c > 7.5%, wbc > 11.0 ×109/l, and crp > 5 mg/l. amongst them, hba1c > 7.5% as indicator of poor glycemic control was the most important independent risk factor of anal abscess recurrence (or=2.68, 95% ci: 1.37-5.25; p < 0.001). the area under the roc curve (auc) of hba1c, crp, and wbc in predicting the risk of abscess recurrence was 0.81, 0.71, and 0.64, respectively (figure 3). 4. discussion this 4-year retrospective single-center study of t2dm patients with an initial treated anal abscess demonstrated a high incidence for anal abscess recurrence (28.6%). as mentioned above, we discovered that amongst a wide range of possible risk factors, the ones consistently linked to recurring anal abscess were: 1. metabolic syndrome, 2. hba1c > 7.5%, 3. wbc > 11.0 ×109/l, and 4. crp levels of more than 5 mg/l. unfavorable glycemic control, described as having hba1c levels of more than 7.5%, was recognized as the most prominent predisposing factor for abscess recurrence in the present study. these findings are supported by previous studies that stated hba1c levels are markedly higher in those with relapse of both diabetic ulcer and anal abscess compared to those without re-occurrence (5, 10). inadequate long-term blood glucose control may hinder healing of wounds, but it might also represent lower patient adherence to different preventative strategies, such as glycemic control self-monitoring and compliance with anal abscess treatment guidelines (11). poor psychological support and patient education and may also be linked to a greater likelihood of anal abscess relapse (12). additionally, we discovered that high crp levels were an established risk factor for re-occurrence of anal abscess. since the patients had no additional inflammatory or infectious disorders during our clinical evaluation, the increased crp upon presentation was most likely due to infections. it was previously shown that increased amount of crp was related to ensuing complications in a long-term analysis of peri-anal abscess (13-15). although some studies have shown that higher crp levels are linked to an elevated risk of sequelae and re-occurrence of the anal abscess, there have not been any formerly published evidence on the prognostic accuracy of crp for anal abscess relapse. eventually, we noticed that culture findings of patients with recurring anal abscess were identical to those of non-recurring patients. abscess cultures frequently feature mixed anaerobic and aerobic microorganisms, as we discovered in our investigation. the skin and the gastrointestinal tract provide the majority of microorganisms in an anal abscess (16). pepto streptococcus spp. and bacteroides spp. were prevalent anaerobic pathogens in individuals, whereas klebsiella this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e69 figure 1: flowchart of patients’ enrollment in the study. figure 2: frequency of perianal abscess recurrence in diabetes mellitus type 2 patients during 4-year follow-up. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. malekpour alamdari et al. 6 figure 3: area under the receiver operating characteristic (roc) curve (auc) of hemoglobin a1c (auc = 0.81), creactive protein (auc = 0.71), and white blood cells (auc = 0.64) in predicting the recurrence of perianal abscess in patients with type 2 diabetes mellitus. pneumoniae, staphylococci spp., and escherichia coli, were prominent aerobic pathogens. t2dm patients are thought to have decreased adaptive and native immunity, according to current findings (17, 18). hence, antibiotic treatment may be explored in all diabetic patients, even if post-surgical antibiotic therapy had a limited function in uncomplicated anal abscess. both anaerobic and aerobic bacteria could be fully covered by empiric antibiotic therapy (19). we propose that, given the considerable risk of recurring anal abscess, preventative programs focusing on cases recognized to be in the high-risk categories would be suitable. this might entail endeavors to inform individuals and the correspondent healthcare professionals on treatments found to be successful in avoiding anal abscess development and relapse. reoccurrence of rectal abscess is not reported to increase the rate of mortality per se, but could remarkably increase morbidity and influence life quality of patients. this event could be even more important as we found that the majority of patients facing with anal abscess are in their youth (45.9 years ± 7.8). of note, we found that the main risk factors of abscess recurrence are directly or indirectly related to metabolic disorders, such as obesity and uncontrolled plasma glucose levels. these variables are considerably preventable and manageable despite being extremely prevalent. hence, the authors suggest that clinicians closely follow up patients with higher risk of abscess recurrence to better control their diabetes mellitus, diets, and physical activity in order to reduce the burden of anal abscess and the resulting health care expenses. 5. strengths and limitations our study had some limitations: first, the relatively small number of included patients; second, the research being performed in a single center; and third, the retrospective arrangement of the study were the main limitations. only 48 t2dm patients with recurrence of anal abscess were identified during 4 years. moreover, the addition of a tertiary center may have resulted in an unwanted selection bias. indeed, we have to declare that our study could possibly face the flowing 2 concerns regarding study bias, if any, as the authors believe they did their best to prevent any bias: 1. selection bias: the presence of missing data can result in selection bias during the course of the study; and 2. confirmation bias: this may occur during the interpretation of study data when the authors, consciously or unconsciously, look for information or patterns in their data that confirm the ideas they already hold. notwithstanding, to the best of our knowledge, this is the first-ever analysis focusing on the distinct risk factors of recurring anal abscess in t2dm patients, which evaluates their prognostic validity for anal abscess re-occurrence. 6. conclusion our findings demonstrate a high rate of anal abscess recurrence within four years in diabetic patients with anal abscess. the presence of metabolic syndrome, elevated wbc count, an increased crp (at the time of diagnosing the first anal abscess) and inadequate glycemic management, were independent risk factors for recurring abscess. 7. declarations 7.1. acknowledgments the authors would like to take this opportunity to thank all the staff of shahid modarres hospital for their effort and cooperation in providing the medical records data to conduct this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e69 7.2. authors’ contributions nma: patient management, patient surgical management, data gathering, drafting, reviewing the article, sa: writing manuscript, data gathering, designation of figures, conducting statistical analysis , fet writing manuscript, data gathering, designation of figures, conducting statistical analysis, mf final review, conceptualization , sb: patient management, patient disease diagnosis, data gathering, writing discussion, fr writing manuscript, data gathering, designation of figures, conducting statistical analysis, final review. 7.3. funding and supports this project did not have any sources of financial support. 7.4. conflict of interest no conflict of interest is declared by the authors of this study. 7.5. sources of funding the funding of this study was provided by shahid beheshti university of medical sciences. references 1. sneider eb, maykel ja. anal abscess and fistula. gastroenterol clin north am. 2013;42(4):773-84. 2. sigmon df, emmanuel b, tuma f. perianal abscess. statpearls. treasure island (fl): statpearls publishing llc.; 2021. 3. chernyadyev sa, ufimtseva ma, vishnevskaya if, bochkarev ym, ushakov aa, beresneva ta, et al. fournier’s gangrene: literature review and clinical cases. urol int. 2018;101(1):91-7. 4. kovalcik pj, peniston rl, cross gh. anorectal abscess. surg gynecol obstet. 1979;149(6):884-6. 5. adamo k, gunnarsson u, eeg-olofsson k, strigård k, brännström f. risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control. int j colorectal dis. 2021;36(5):9991005. 6. adamo k, sandblom g, brännström f, strigård k. prevalence and recurrence rate of perianal abscess–a population-based study, sweden 1997-2009. int j colorectal dis. 2016;31(3):669-73. 7. akkapulu n, dere ö, zaim g, soy he, özmen t, doğrul ab. a retrospective analysis of 93 cases with anorectal abscess in a rural state hospital. ulus cerrahi derg. 2015;31(1):5-8. 8. devaraj b, khabassi s, cosman bc. recent smoking is a risk factor for anal abscess and fistula. dis colon rectum. 2011;54(6):681-5. 9. almeida msc, sousa filho lf, rabello pm, santiago bm. international classification of diseases 11th revision: from design to implementation. rev saude publica. 2020;54:104. 10. wei pl, keller jj, kuo lj, lin hc. increased risk of diabetes following perianal abscess: a population-based follow-up study. int j colorectal dis. 2013;28(2):235-40. 11. xiang j, wang s, he y, xu l, zhang s, tang z. reasonable glycemic control would help wound healing during the treatment of diabetic foot ulcers. diabetes ther. 2019;10(1):95-105. 12. dudukgian h, abcarian h. why do we have so much trouble treating anal fistula? world j gastroenterol. 2011;17(28):3292-6. 13. silvestre j, rebanda j, lourenço c, póvoa p. diagnostic accuracy of c-reactive protein and procalcitonin in the early detection of infection after elective colorectal surgery a pilot study. bmc infect dis. 2014;14:444. 14. kwak ms, kim kj, park sh, yang dh, ye bd, byeon js, et al. elevated c-reactive protein is associated with disease progression in patients with mild crohn’s disease. springerplus. 2016;5(1):878. 15. hsieh mh, lu ya, kuo g, chen cy, sun wc, lin y, et al. epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study. clinics (sao paulo). 2019;74:e638. 16. liu ck, liu cp, leung ch, sun fj. clinical and microbiological analysis of adult perianal abscess. j microbiol immunol infect. 2011;44(3):204-8. 17. berbudi a, rahmadika n, tjahjadi ai, ruslami r. type 2 diabetes and its impact on the immune system. curr diabetes rev. 2020;16(5):442-9. 18. graves dt, kayal ra. diabetic complications and dysregulated innate immunity. front biosci. 2008;13:1227-39. 19. sözener u, gedik e, kessaf aslar a, ergun h, halil elhan a, memikoğlu o, et al. does adjuvant antibiotic treatment after drainage of anorectal abscess prevent development of anal fistulas? a randomized, placebocontrolled, double-blind, multicenter study. dis colon rectum. 2011;54(8):923-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strengths and limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e2 or i g i n a l re s e a rc h a clinical score for predicting the paroxysmal supraventricular tachycardia’s recurrence risk; a retrospective cross-sectional study chaiyaporn yuksen1, welawat tienpratarn1∗, rungrawin promkul1, chetsadakon jenpanitpong1, sorawich watcharakitpaisan1, jenjira yaithet2, viruji phonphom1 1. department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, bangkok, thailand. 2. chakri naruebodindra medical institute, faculty of medicine ramathibodi hospital, mahidol university, 111 moo 14, bang pla, bang phli, samut prakarn 10540, thailand. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: identifying prognostic variables associated with the probability of recurrent paroxysmal supraventricular tachycardia (psvt) would aid decision-making regarding disposition of the patients. this study aims to develop a clinical scoring system to predict psvt recurrence after adenosine administration in the emergency department (ed). methods: this retrospective cross-sectional study was conducted on patients who were referred to the emergency department of ramathibodi hospital, a university-affiliated super-tertiary care hospital in bangkok, thailand, with diagnosis of psvt during a 10-year period from 01 january 2010 until 31 december 2020. the cases were divided into recurrent and non-recurrent psvt based on the response to standard treatment and the independent predictors of recurrence were studied using multivariable logistic regression analysis. results: 264 patients were diagnosed with psvt and successfully converted by adenosine. 24 (9.1%) had recurrent psvt, and 240 (90.9%) had no recurrent psvt in the same ed visit. the risk of psvt recurrence in ed corresponded with the history of hypertension (p = 0.059), valvular heart disease (p = 0.052), heart rate ≥ 100 (p = 0.012), and systolic blood pressure < 100 after electrocardiogram (ecg) converted to sinus rhythm (p = 0.022) and total dose of adenosine (p = 0.002). we developed a clinical prediction score of psvt recurrence with an accuracy of 79.5%. a score of 0 (low risk), 1–2 (moderate risk), and > 2 (high risk) had a positive likelihood ratio (lr+) of 0.31, 0.56 and 2.33, respectively. conclusion: it seems that, using the psvt recurrence score we could screen the high-risk patients for psvt recurrence (score>2) who need to be observed for at least 6-12 hours and receive cardiologist consultation in ed. in addition, the moderate and low-risk group (score 0-2) need to be observed for 1 hour and can be discharged from ed. keywords: tachycardia, supraventricular; recurrence; emergency service, hospital; adenosine; clinical decision rules cite this article as: yuksen c, tienpratarn w, promkul r, jenpanitpong c, watcharakitpaisan s, yaithet j, phonphom v. a clinical score for predicting the paroxysmal supraventricular tachycardia’s recurrence risk; a retrospective cross-sectional study. arch acad emerg med. 2023; 11(1): e2. https://doi.org/10.22037/aaem.v11i1.1825. 1. introduction supraventricular tachycardia (svt) is defined as atrial and ventricular rates exceeding 100 beats per minute (bpm) at rest. its mechanism involves tissue from the his bundle or above (1, 2). svt, which includes atrioventricular nodal reen∗corresponding author: welawat tienpratarn; department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, 270 rama vi road, thung phaya thai, ratchathewi, bangkok, thailand, 10400. e-mail: pedz_welawat@hotmail.com, orcid: https://orcid.org/0000-00016577-5921. trant tachycardia (avnrt), atrioventricular reentrant tachycardia (avrt), and atrial tachycardia (at), is a common tachyarrhythmia that causes approximately 50,000 emergency department (ed) visits annually in the united states of america (3). paroxysmal supraventricular tachycardia (psvt) is a clinical syndrome characterized by the presence of a narrow qrs complex, regular, and tachycardic electrocardiograph with abrupt onset and termination (1). the diagnosis and treatment of psvt are often made in the emergency department (ed). adenosine has been commonly used as a diagnostic and therapeutic agent for psvt since the 1990s (4, 5). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index c. yuksen et al. 2 according to the international guidelines for managing svt by the american heart association (aha) and the european society of cardiology (esc), adenosine is still recommended as a first-line treatment option for subjects with hemodynamically stable svt (2, 6). an initial dose of 6 mg should be administered intravenously over 1-2 seconds, then the second dose of 12 mg can be repeated once if there is no response within 1-2 minutes (1). efficacy of initial and repeat dose of adenosine on sinus rhythm conversion reported by previous studies is approximately 90% (7). although adenosine yields high efficacy on sinus rhythm conversion and nearly half of svt patients were discharged from the ed without clinical follow-up (3), two observational studies revealed that the number of ed revisits due to recurrent psvt was approximately 30%, with total number of revisits ranging from 70-90 times over three years (8, 9). identifying prognostic variables associated with the probability of recurrent psvt after adenosine administration would aid the clinicians in deciding to hospitalize or discharge the patient. this strategy may reduce ed overcrowding, unnecessary resource utilization, and complications related to unsuitable management (9, 10). previous studies have found that older patients, those with diabetes, cardiovascular diseases, or illicit drug use, and those with heart rates more than 200 bpm before treatment have a higher probability of psvt recurrence after adenosine administration (8, 9, 11, 12). however, there have been no prediction tools to assess the probability of recurrent psvt. immediately discharging the patient after a successful conversion with adenosine is a challenging decision for the emergency physicians. there is no clinical prediction score to predict the recurrence of psvt after a successful conversion with adenosine and facilitating judgment regarding patient disposition. in groups with low risk of recurrence, we hypothesized that we could immediately discharge the patient from ed. this study aims to develop a clinical scoring to predict psvt recurrence after adenosine administration in the ed. 2. methods 2.1. study design and settings this retrospective cross-sectional study was conducted on patients who were referred to the emergency department of ramathibodi hospital, a university-affiliated super-tertiary care hospital in bangkok, thailand, with diagnosis of psvt during a 10-year period from 01 january 2010 until 31 december 2020. the cases were divided into recurrent and nonrecurrent psvt based on the response to standard treatment and the independent predictors of recurrence were studied using multivariate analysis. this study was approved by the faculty of medicine, committee on human rights related to research involving human subjects, ramathibodi hospital, mahidol university (coa. no mura2021/463). the ethics committee waived obtaining consent for this research as the patients’ medical records were used for data gathering, and a statement covering patient data confidentiality and compliance with the declaration of helsinki was provided. 2.2. participants patients with the final diagnosis of supraventricular tachycardia (based on icd-10 i -471 definition) in the hospital database and emergency medical record (emr) were included. patients were included if they were aged >15 years, visited the emergency department with the diagnosis of psvt, and converted with adenosine in ed. the exclusion criteria were psvt not responding to adenosine or patients having a concurrent medical disease requiring admission. 2.3. data gathering the study variables were recorded for all eligible patients, including the baseline characteristics and potential prognostic factors for recurrent psvt. clinical variables included gender, age, vital signs (heart rate, systolic blood pressure before receiving adenosine and after conversion to normal sinus rhythm), underlying diseases (history of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, dyslipidemia, and cardiac arrhythmia), clinical symptoms (chest pain, syncope, and palpitations), tobacco use, illicit drug use, previous treatment with the antiarrhythmic agent, the dose of adenosine used for treatment, and time to recurrence in the same visit. recurrent psvt was defined as the new onset of psvt after being successfully converted to normal sinus rhythm using adenosine in the same ed visit. 2.4. outcome measures the outcome of interest was that psvt failed to respond to adenosine in the first, second, or third dose of adenosine in ed. we defined “the recurrence group” as the patients whose transient response to adenosine and return to normal sinus rhythm on electrocardiogram was converted to psvt during the same ed visit. the non-recurrence group includes the patients who responded to adenosine in the first, second, or third dose, and electrocardiogram did not convert to psvt in the same visit to ed. 2.5. psvt management all psvt patients received 6 mg of adenosine using a double syringe technique (bolus adenosine via a large peripheral vein immediately followed by 10 ml of saline flush) during electrocardiogram (ecg) monitoring. if the ecg converted to normal sinus rhythm, the patient was sent for 6-12 hours of observation with laboratory blood testing in an observational area in ed. otherwise, the psvt patient who did not this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e2 respond to the first dose of adenosine (within 10 seconds) received the second dose of 12 mg. if the ecg converted to normal sinus rhythm, the patient was sent for 6-12 hours of observation with laboratory blood testing in an observational area in ed. furthermore, the psvt patient who did not respond to the second dose of 12 mg adenosine (within 10 seconds) received the third dose of 12 mg. if the ecg converted to normal sinus rhythm, the patient was sent for 6-12 hours of observation with laboratory blood testing in an observational area in ed. the patients who did not respond to a total of three doses of adenosine were sent to cardiologist consultation and were not included in our study. after 6-12 hours of observation, the patients who did not have a recurrence of psvt were discharged and given an appointment for radiofrequency catheter ablation with the cardiologist. the patients who had recurrent psvt during the observation received cardiologist consultation for in-patient care. 2.6. statistical analysis we used stata version 16.0 (statacorp, college station, tx, usa) to calculate the sample size. a pilot study was performed to determine the rates of recurrent psvt and nonrecurrent psvt. the assumptions were as follows: alpha = 0.05 (two-sided test), power of sample size = 0.8, and the ratio of sample size was 1:10. the sample size of 180 was obtained in the non-recurrent psvt group, and the sample size of 18 was calculated for the recurrent psvt group. the data were analyzed using stata version 16.0. the continuous data are presented as mean (standard deviation) or median (interquartile range), and categorical data are presented as frequency (%). all study variables were compared between recurrent and non-recurrent psvt using the exact probability test for categorical variables and the t-test for continuous variables. we used the univariable logistic regression to discriminate variables corresponding to recurrence of psvt and reported the results using p-value, the area under the receiver operating characteristic curve (auroc), and 95% confidence interval (ci). clinical predictors with high discriminative performance, statistical significance, and clinical relevance were analyzed using multivariable logistic regression and reported with odds ratios. the coefficients for each level of clinical predictor were divided by the smallest coefficient of the model and rounded to the nearest 0.5, resulting in an item risk score. the coefficients were changed into item scores and added together resulting in a single score, and patients were classified into low-, moderate-, and high-risk groups according to this score and results were presented as positive likelihood ratio, 95% ci, and p-value. discrimination of the prediction scores was presented as auroc and 95% ci. calibration of the prediction was tested using hosmer–lemeshow goodness-of-fit test. the scorepredicted risk of recurrent psvt and the observed risk were then compared in a graph. 3. results 3.1. baseline characteristics of studied cases 264 patients diagnosed with psvt who underwent treatment with adenosine in ed were enrolled in the study. 24 (9.1%) had recurrent psvt in the same ed visit. based on the univariable logistic regression analysis, history of hypertension (auroc= 59%, 95%ci: 49% 70%, p = 0.059), history of valvular heart disease (auroc= 55%, 95%ci: 48% 62%, p = 0.052), heart rate ≥ 100 after ecg converted to sinus rhythm (auroc= 63%, 95%ci: 53% 74%, p = 0.012), systolic blood pressure < 100 after ecg converted to sinus rhythm (auroc= 57%, 95%ci: 49% 64%, p = 0.022), and need for full dose of adenosine (auroc= 67%, 95%ci: 56%78%, p = 0.002) had high discriminative performance (auroc) and were significantly and clinically associated with recurrent psvt (table 1). 3.2. multivariable logistic regression analysis multivariable logistic regression analysis included the five prognostic factors form table 1 to predict recurrence of psvt in ed (table 2). based on multivariable logistic regression analysis, history of hypertension (or=2.36, 95% ci: 0.92 6.05, p=0.074), history of valvular heart disease (or=4.62, 95% ci: 0.97 22.03, p=0.055), heart rate ≥ 100 after ecg converted to sinus rhythm (or=3.68, 95% ci: 1.44 9.35, p=0.006), systolic blood pressure < 100 after ecg converted to sinus rhythm (or=4.73, 95% ci: 1.08 20.85, p=0.040) and need for full dose of adenosine (2n d dose of 12 mg adenosine or=3.66, 95% ci: 1.24 10.80, p=0.019 and 3r d dose of 12 mg adenosine or=3.65, 95% ci: 1.11 12.04, p=0.034) were independent predictors of psvt recurrence. the auroc was 79.5% (95% ci: 64.5%85.5%) for the ability of the clinical risk score to predict recurrent psvt (figure 1). 3.3. designing a predictive model the coefficients for each level of clinical predictor were divided by the smallest coefficient of the model and rounded to the nearest 0.5, resulting in an item risk score, with scores ranging from 0 to 2 (table 2). figure 2 shows the distribution plot of the score in predicting recurrent psvt and the calibration of the prediction model using the hosmer–lemeshow goodness-of-fit test. the score-predicted risk of recurrent psvt and the observed risk were then compared in a graph. the score-predicted risk increased in close association with the observed risk. finally, the risk scores were categorized into three groups: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index c. yuksen et al. 4 table 1: comparing the baseline characteristics of studied cases between patients with and without recurrent paroxysmal supraventricular tachycardia (psvt) variable recurrent psvt p auc 95%ci yes (n = 24) no (n = 240) gender female 13 (54.2) 162 (67.5) 0.138 0.43 0.33 0.54 age (year) mean ± sd 56.7 ± 17.2 52.3 ± 16.7 0.215 0.59 0.47 0.72 bmi mean ± sd 23.52 ± 5.00 24.72 ± 6.39 0.372 0.44 0.30 – 0.58 vital signs (baseline) hr (/minute) 181.4 ± 19.7 176.9 ± 21.2 0.319 0.57 0.46 0.69 sbp (mmhg) 131.6 ± 27.7 124.9 ± 22.1 0.165 0.56 0.43 0.70 vital signs (after conversion) hr (/minute) 103.6 ± 14.2 93.6 ± 14.8 0.002 0.69 0.57 0.80 hr ≥ 100 (/min) 15 (62.5) 87 (36.3) 0.012 0.63 0.53 0.74 sbp (mmhg) 131.9 ± 24.1 127.1 ± 20.7 0.291 0.57 0.43 0.71 sbp < 100 mmhg 20 (83.3) 231 (96.3) 0.022 0.57 0.49 0.64 underlying disease ht 12 (50.0) 76 (31.67) 0.059 0.59 0.49 0.70 dm 7 (29.17) 47 (19.58) 0.196 0.55 0.45 0.64 svt 12 (50.0) 109 (45.42) 0.413 0.52 0.42 0.63 cad 2 (8.33) 20 (8.33) 0.618 0.50 0.44 0.56 paroxysmal af 2 (8.33) 8 (3.33) 0.228 0.53 0.47 0.58 history of vhd 3 (12.5) 7 (2.92) 0.052 0.55 0.48 0.62 thyroid disease 3 (12.5) 14 (5.83) 0.192 0.53 0.46 0.60 chf 0 (0.0) 1 (0.42) 0.909 0.50 0.49 0.50 antiarrhythmic drug 13 (54.17) 86 (35.83) 0.063 0.60 0.49 0.70 chest pain 1 (4.17) 29 (12.08) 0.211 0.46 0.42 0.51 syncope 2 (8.33) 17 (7.08) 0.534 0.51 0.45 0.57 palpitations 23 (95.83) 230 (95.83) 0.657 0.50 0.46 0.54 svt ablation 4 (16.67) 20 (8.33) 0.160 0.54 0.46 0.62 adenosine 1s t dose 10 (41.67) 181 (75.42) 2n d dose 8 (33.33) 35 (14.58) 0.002 0.67 0.56 0.78 3r d dose 6 (25.00) 24 (10.00) data are presented as mean ± standard deviation (sd) or frequency (%). auc: area under the receiver operating characteristic (roc) curve as discrimination power; ci: confidence interval. hr: heart rate; sbp: systolic blood pressure; bmi: body mass index; ht: hypertension; vhd: valvular heart disease; dm: diabetes mellitus; svt: supraventricular tachycardia; cad: coronary artery disease; af: atrial fibrillation; chf: congestive heart failure. score =0 (low risk), score 1–2 (moderate risk), and score >2 (high risk). the mean score of patients with recurrent psvt was significantly higher (2.90 ± 1.58 vs. 1.26 ± 1.18; p < 0.001). the positive likelihood ratio of recurrent psvt in low-, moderate-, and high-risk cases for recurrence were 0.31, 0.56, and 2.53, respectively (table 3). 4. discussion this study demonstrated that the independent predictive factors of recurrent psvt were history of hypertension (1 point), history of valvular heart disease (2 points), heart rate ≥ 100 after conversion to sinus rhythm (1.5 points), systolic blood pressure < 100 after conversion to sinus rhythm (2 points), and second or third dose of adenosine (1.5 points). the psvt patient was categorized as high-risk (score>2), with a positive likelihood ratio of recurrent psvt in the same ed visit of 2.33. there is a high risk of psvt recurrence in ed. more than half of patients in this group (53%) had recurrence within 1 hour, and 47% had recurrence within 2-19 hours. these patients need to be admitted and remain under observation for at least 6-12 hours and receive cardiologist consultation for radiofrequency catheter ablation consideration during the same visit due to psvt presentation. the psvt patient was categorized as low-risk (score =0) and moderate-risk (score 1-2) with a positive likelihood ratio of recurrent psvt of 0.31 and 0.56, respectively. (only two patients were in the low-risk group and five in the moderaterisk group). these groups of patients must remain under this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e2 table 2: the independent predictors of recurrent paroxysmal supraventricular tachycardia (psvt) and the assigned item score based on multivariable logistic regression predictors adjusted or 95%ci p-value coefficient* score history of ht no 1.00 reference 0 yes 2.36 0.92 – 6.05 0.074 0.86 1 history of vhd no 1.00 reference 0 yes 4.62 0.97 – 22.03 0.055 1.53 2 hr ≥ 100 (mmhg)# no 1.00 reference 0 yes 3.68 1.44 – 9.35 0.006 1.30 1.5 sbp < 100 (mmhg)# no 1.00 reference 0 yes 4.73 1.08 – 20.85 0.040 1.55 2 adenosine dose 1s t 1.0 reference 0 2n d 3.66 1.24 – 10.80 0.019 1.30 1.5 3r d 3.65 1.11 12.04 0.034 1.30 1.5 # after conversion to sinus rhythm; * coefficients from multivariable logistic regression. or: odds ratio; vhd: valvular heart disease; ht: hypertension; hr: heart rate; sbp: systolic blood pressure; ci: confidence interval. table 3: likelihood of recurrent paroxysmal supraventricular tachycardia (psvt) in different probability categories based on the scores of the designed prediction scoring system probability categories score recurrent psvt lr+ 95%ci p yes (n = 24) no (n = 240) low 0 2 (8.4) 80 (33.3) 0.31 0.08 – 1.18 0.031 moderate 1-2 5 (20.8) 108 (45.0) 0.56 0.25 1.25 0.085 high > 2 17 (70.8) 52 (21.7) 2.33 1.50 3.61 0.001 data are presented as frequency (%).lr+: positive likelihood ratio; ci: confidence interval. figure 1: the area under the receiver operating characteristic (roc) curve of the designed clinical risk score in predicting the risk of recurrent paroxysmal supraventricular tachycardia (psvt). observation in ed for at least 1 hour, be considered for discharge, and make an appointment with the cardiologist for follow-up. patients categorized as lowand moderate-risk can be discharged from ed. in this study, 90.9 % of psvt cases could be discharged after 1-hour observation in ed. it is in concordance with the study of luber et al., which showed that 71% of patients were discharged from the ed (11). sawhney et al. showed that only 34% of patients had specialist referrals (13). the study of honarbakhsh et al. showed that paramedics could successfully treat psvt (81%) in the prehospital setting and reduce healthcare costs for transfer to ed (discharge at the prehospital setting) without compromising patient care (14). the treatment of choice for psvt is slow pathway modification (spm). in this study, the success rate of adenosine administration was 100%. a study by wegner et al. showed around 95% success using adenosine (15). the prognostic factors’ effect on the recurrence of psvt in this study is concordant with the study of piyanuttapull et al. about the recurrence of psvt within 90 days, low systolic blood pressure (sbp < 90 mmhg) and valvular heart disease were associated with recurrence of psvt (8). in this study, we also found that heart rate ≥ 100 and systolic blood pressure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index c. yuksen et al. 6 figure 2: distribution plot of recurrent paroxysmal supraventricular tachycardia (psvt) based on the designed scoring system and the calibration curve of the prediction model using the hosmer–lemeshow goodness-of-fit test. < 100 after ecg converted to sinus rhythm and the total dose of adenosine were associated with recurrence of psvt. there is no result about this prognostic factor in other studies. in the lowand moderate-risk groups for psvt recurrence, the emergency physician can discharge the patient after 1 hour of observation in ed instead of 6-12 hours following the old ramathibodi psvt protocol. the new protocol can reduce ed overcrowding, resource utilization in ed, and overall healthcare costs in ed. the study by thomas a. dewland et al. showed that psvt patients treated with catheter ablation had a significantly lower psvt recurrence rate in ed (hr= 0.25, 95% ci: 0.10-0.62, p = 0.003) (9). the new protocol should include cardiologist consultation for catheter ablation to reduce ed revisit. the strength of our model is predicting psvt recurrence in the same ed visit for selecting the patients requiring disposition. the other existing model focuses on the recurrence of psvt within 90 days and not the same ed visit. 5. limitation this study has some limitations. first, this was a retrospective study. there is reviewer bias in reviewing the data of emergency medical records. some missing data affected the accuracy of the study. second is the limitation in the number of patients in the recurrent group (n=24). it is a small sample size but enough to have statistically significant power. third, this study was conducted in ramathibodi hospital, and internally validated within the same dataset. external validation with different datasets may be required for the next project. 6. conclusion it seems that, using the psvt recurrence score we could screen the high-risk patients for psvt recurrence (score>2) who need to be observed for at least 6-12 hours and receive cardiologist consultation in ed. in addition, the moderateand low-risk groups (score 0-2) need to be observed for 1 hour and can be discharged from ed. 7. declarations 7.1. acknowledgments not applicable. 7.2. funding source no funding was obtained for this study. 7.3. authors’ contribution all authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. 7.4. ethical considerations this study was approved by the faculty of medicine, committee on human rights related to research involving human subjects, ramathibodi hospital, mahidol university (coa. mura2021/463). the ethics committee did not require consent for this research because medical records were reviewed and a statement covering patient data confidentiality and compliance with the declaration of helsinki was provided. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e2 7.5. availability of data and material the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. 7.6. conflict of interest the authors declare that they have no competing interests. references 1. page rl, joglar ja, caldwell ma, calkins h, conti jb, deal bj, et al. 2015 acc/aha/hrs guideline for the management of adult patients with supraventricular tachycardia: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart rhythm society. circulation. 2016;133(14):e506-74. 2. brugada j, katritsis dg, arbelo e, arribas f, bax jj, blomström-lundqvist c, et al. 2019 esc guidelines for the management of patients with supraventricular tachycardia the task force for the management of patients with supraventricular tachycardia of the european society of cardiology (esc) developed in collaboration with the association for european paediatric and congenital cardiology (aepc). eur heart j. 2020;41(5):655-720. 3. murman dh, mcdonald aj, pelletier aj, camargo jr ca. us emergency department visits for supraventricular tachycardia, 1993–2003. acad emerg med. 2007;14(6):578-81. 4. faulds d, chrisp p, buckley mm. adenosine. an evaluation of its use in cardiac diagnostic procedures, and in the treatment of paroxysmal supraventricular tachycardia. drugs. 1991;41(4):596-624. 5. cairns cb, niemann jt. intravenous adenosine in the emergency department management of paroxysmal supraventricular tachycardia. ann emerg med. 1991;20(7):717-21. 6. panchal ar, bartos ja, cabañas jg, donnino mw, drennan ir, hirsch kg, et al. part 3: adult basic and advanced life support: 2020 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2020;142(16_suppl_2):s366-s468. 7. brubaker s, long b, koyfman a. alternative treatment options for atrioventricular-nodal-reentry tachycardia: an emergency medicine review. j emerg med. 2018;54(2):198-206. 8. piyanuttapull s, patarananakul p. recurrence rate of psvt (paroxysmal supraventricular tachycardia) in rajavithi emergency department. j med assoc thai. 2013;96(suppl 3):s47-53. 9. dewland ta, oesterle a, stein j, marcus gm. health care utilization among adenosine-sensitive supraventricular tachycardia patients presenting to the emergency department. j interv card electrophysiol. 2017;49(2):103-9. 10. tangkulpanich p, yuksen c, kongchok w, jenpanitpong c. clinical predictors of emergency department revisits within 48 hours of discharge; a case control study. arch acad emerg med. 2021;9(1):e1. 11. luber s, brady wj, joyce t, perron ad. paroxysmal supraventricular tachycardia: outcome after ed care. am j emerg med. 2001;19(1):40-2. 12. althunayyan sm, khan aa, samarkandi oa. emergency department visits for paroxysmal supraventricular tachycardia in saudi arabia. saudi j anaesth. 2018;12(4):521-8. 13. sawhney v, corden b, abdul-mukith k, harris t, schilling rj. are patients admitted to emergency departments with regular supraventricular tachycardia (svt) treated appropriately? clin med (lond). 2013;13(2):146-8. 14. honarbakhsh s, baker v, kirkby c, patel k, robinson g, antoniou s, et al. safety and efficacy of paramedic treatment of regular supraventricular tachycardia: a randomised controlled trial. heart. 2017;103(18):1413-8. 15. wegner fk, habbel p, schuppert p, frommeyer g, ellermann c, lange ps, et al. predictors of avnrt recurrence after slow pathway modification a case control study. int heart j. 2021;62(1):72-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e31 rev i ew art i c l e effect of oral care with povidone-iodine in the prevention of ventilator-associated pneumonia; a systematic review and meta-analysis amir emami zeydi1, arman parvizi2, soudabeh haddadi2, samad karkhah3,4, seyed javad hosseini5, amirabbas mollaei3,4, mahbobeh firooz5, shahin ramezani6, joseph osuji7, pooyan ghorbani vajargah3,4∗, shadi dehghanzadeh8 † 1. department of medical-surgical nursing, nasibeh school of nursing and midwifery, mazandaran university of medical sciences, sari, iran. 2. anesthesiology research center, department of anesthesiology, alzahra hospital, guilan university of medical sciences, rasht, iran. 3. department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 4. burn and regenerative medicine research center, guilan university of medical sciences, rasht, iran. 5. department of nursing, esfarayen faculty of medical sciences, esfarayen, iran. 6. student research committee, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 7. school of nursing and midwifery, faculty of health, community, and education, mount royal university, calgary, ab, canada. 8. department of nursing, college of nursing and midwifery, rasht branch, islamic azad university, rasht, iran. received: january 2023; accepted: february 2023; published online: 4 april 2023 abstract: introduction: ventilator-associated pneumonia (vap) is one of the most common nosocomial infections affecting onethird of patients with mechanical ventilation. this study aimed to synthesize available evidence regarding the effect of treatment with povidone-iodine (pi) among adult patients admitted to intensive care units (icus) for the prevention of vap. methods: an extensive search was conducted in online databases, including pubmed, web of science and scopus, from the earliest records until january 1, 2023. stata software v14 was used for statistical analysis. publication bias was assessed via funnel plot, begg’s and egger’s tests. a p-value less than 0.1 was considered statistically significant for publication bias value. results: four studies were included in the meta-analysis. three studies showed rhat pi decreased vap compared to the placebo group, but it was not statistically significant (rr: 0.61, 95%ci: 0.25 to 1.47, z=1.10, p=0.27, i2 :71.5%). one study compared the effect of pi with chlorhexidine on the rate of vap, the difference between which was not statistically significant (rr: 1.50, 95%ci: 0.46 to 4.87, z=0.67, p=0.50, i2 :0). two studies demonstrated that the use of pi intervention compared to placebo decreased the average length of stay in icu; however, it was not statistically significant (wmd: -0.35, 95%ci:-3.90 to 3.20, z=0.19, p=0.85, i2 :0). also, three studies showed that using pi had almost no effect on mortality rate compared to placebo (rr: 1.05, 95%ci: 0.66 to 1.53, z=0.8, p=0.27, i2 :29.0%). conclusion: more rigorously designed randomized clinical trials and further evidence are required to make a better decision/comparison about using pi as a suitable choice for preventing vap among adult patients admitted to the icu. keywords: oral hygiene; pneumonia, ventilator-associated; primary prevention; povidone-iodine; meta-analysis cite this article as: emami zeydi a, parvizi a, haddadi s, karkhah s, et al. effect of oral care with povidone-iodine in the prevention of ventilator-associated pneumonia; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e31. https://doi.org/10.22037/aaem.v11i1.1874. ∗corresponding author: pooyan ghorbani vajargah; nursing and midwifery school of shahid dr beheshti, hamidyan shahrak, shahid dr beheshti ave., rasht, guilan, iran. email: poyan.ghorbani@gmail.com, orcid: https://orcid.org/0000-0003-3365-2681. † corresponding author: shadi dehghanzadeh; department of nursing, college of nursing and midwifery, rasht branch, islamic azad university, rasht, iran. email: dehghanzadeh@iaurasht.ac.ir, orcid: https://orcid.org/00000001-5979-590x. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. emami zeydi et al. 2 1. introduction ventilator-associated pneumonia (vap) is one of the most common nosocomial infections in intensive care units (icus), affecting one-third of patients with mechanical ventilation (1, 2). despite advances in diagnosis, treatment, and nursing care, vap is still a major cause of mortality and morbidity in mechanically ventilated icu patients, potentially increasing the length of icu and hospital stay and healthcare costs (3). therefore, preventing vap is highly desirable and is of utmost importance for improving the quality of care and patient outcomes (4). oral care interventions effectively prevent and treat vap in critically ill mechanically ventilated patients (2, 5). previous evidence suggests a wide range of oral preventive measures, from brushing to using various topical/oral antimicrobial agents such as sodium bicarbonate, chlorhexidine, and povidone-iodine (pi) (2, 6-9). among these, pi has been suggested as one of the best antimicrobial agents in reducing the incidence of respiratory infections such as vap (10, 11). however, there is limited and sometimes contradictory evidence about the efficacy of oral care with pi in the prevention of vap (6, 10, 12, 13). for example, a randomized controlled trial (rct) study in france found that in comparison with placebo, using oropharyngeal pi preventive oral care was not associated with a significant reduction in the incidence of vap, as well as the length of icu and hospital stay, and 90day mortality in mechanically ventilated patients (6). in contrast, another rct study in france showed that oropharyngeal decontamination using pi was associated with a significant reduction in the incidence of vap compared with the use of normal saline and placebo (10). based on the above-metioned points, this study aimed to synthesize available evidence regarding the effect of treatment with pi in preventing vap among adult patients admitted to the icu with mechanical ventilation. 2. methods 2.1. study registration and reporting this systematic review and meta-analysis was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist (14). population, intervention, comparison, and outcomes (pico) of the study are presented in table 1. based on pico, the present meta-analysis assessed the effect of treatment with pi compared with control groups (including both placebo and chlorhexidine) in preventing vap among adult patients admitted to the icu with mechanical ventilation. 2.2. search strategy an extensive search was conducted in online databases, including pubmed, web of science and scopus, using the keywords extracted from medical subject headings (mesh) "ventilator-associated pneumonia", "pneumonia", "intubation", "mechanical ventilation", "oral hygiene", "oral health", "oral care", "mouth care", "antiseptic decontamination", "prevention", "intensive care unit", "critical care", "icu", "povidone-iodine", and "betadine", from the earliest records up to january 1, 2023. the search strategy is presented in table 1. the gray literature, such as conference presentations, expert opinions, dissertations, research and committee reports, and ongoing research, were sought in the present meta-analysis. gray literature refers to papers not controlled by commercial publishers but produced in print and electronic formats (15). 2.3. inclusion and exclusion criteria full-length, peer-reviewed published studies with rct design with a primary focus on evaluating the clinical efficacy of oral care with pi compared with control groups (including using placebo or other antibacterial mouth rinses or methods for oral care) in prevention of vap among adult patients admitted to the icu with mechanical ventilation were included. letters to the editor, opinions, case reports, conference abstracts, reviews, and studies lacking sufficient information for calculating desired parameters were excluded from the study. 2.4. study selection the study selection process was performed using the endnote x8 software. two researchers independently performed steps 1) removing duplicate articles, 2) screening all the studies by title and abstract, and 3) evaluating the full text of the articles. the researchers assessed a list of included studies’ references to prevent any relevant references from being missed in the database searches. any disagreements between researchers were resolved during discussions with the entire research team. 2.5. data extraction and risk of bias version 2 of the cochrane risk-of-bias tool for randomized trials (rob 2) was used to assess risk of bias of included studies. this tool involves random allocation sequence items, random sequence generation, allocation concealment, the blinding of participants and personnel, the blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. the risk of bias was divided into three categories: high, low, and, unclear (16). information such as first author’s name, year of publication, location, patient types, number of patients, type/number of controls, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e31 table 1: search strategy terms pico keywords #* search terms population patients admitted to the icu with mechanical ventilation with ventilator-associated pneumonia 1 “intubation” or “mechanical ventilation” or “prevention” or “intensive care unit” or “critical care” or “icu” intervention povidone-iodine 2 "povidone-iodine" or "betadine" or “oral care” or “mouth care” or “oral hygiene” or “oral health” or “antiseptic decontamination” comparison control groups including placebo and chlorhexidine outcome clinical effectiveness, mortality, and duration of icu admission 3 “ventilator associated pneumonia” or “pneumonia” or “vap” * #1, #2, and #3 combined with “and” operator. to widen search results and avoid missing data, terms for comparison and outcomes were not included in the search strategy. icu: intensive care unit. number of cases, mean age, length of stay in the icu, mortality, and treatment outcome were extracted from included studies using a predesigned extraction form. data extraction and quality assessment of included studies were performed by two authors, independently. 2.6. targeted outcomes targeted outcomes were the clinical efficacy of oral care with pi compared with control groups (including using placebo or other antibacterial mouth rinses or methods for oral care) in prevention of vap, reducing length of stay in the icu, and decreasing patients’ mortality among adult patients admitted to the icu with mechanical ventilation. 2.7. data synthesis the stata software, v14, was used for statistical analysis. outcome estimation was performed using risk ratio (rr) for vap incidence and mortality rate and weighted mean difference (wmd) for the average length of stay in icu with 95% confident interval (ci). after extracting data from studies such as rr, lower and upper confidence intervals, and natural log (ln), each of them was calculated. then, the pooled effect size of vap and mortality incidences were reported based on the random effect model with the inverse variance (iv ) method. wmd as the pooled effect size of an average length of stay in icu was reported based on means, standard deviations, and sample sizes of vap intervention and placebo groups via fixed effect model and iv method. an i2 value of 25% was considered a low heterogeneity, 50% a moderate heterogeneity, and 75% a high heterogeneity. publication bias was assessed via funnel plot, and begg’s and egger’s tests. a p-value less than 0.1 was considered statistically significant for publication bias. sensitivity analysis was performed for the primary outcome (vap) based on three studies that compared pi and placebo groups. 3. results 3.1. study selection a total of 1,912 articles were obtained through database searches, and one was obtained via hand-searching of the references. then, 94 duplicate records were removed. after screening the titles and abstracts of the articles, 1,477 studies were not in line with the purpose of the present study, and 318 studies were non-interventional. after evaluating the full text of the remaining 13 articles, 8 studies were removed due to inappropriate study design or outcomes, and one was removed due to a lack of desired information. finally, this systematic review and meta-analysis included four studies (6, 10, 12, 13) (figure 1). 3.2. included studies characteristics four studies (6, 10, 12, 13) were included in the final analysis. all included studies (6, 10, 12, 13) had rct design. out of 377 patients, 178 were in the intervention group, and 199 were in the control group. placebo and chlorhexidine were used in the control groups in three (6, 10, 12) and one (13) studies, respectively. most patients (62.10%) were male, with a mean age of 47.07 ± 15.71 years. the basic characteristics of the included studies are shown in table 2. 3.3. risk of bias or quality of included studies the generation of a randomization sequence was low risk in two studies (12, 13), while two did not mention generating a randomization sequence (6, 10). the included articles did not determine random allocation concealment. two studies were double-blind (6, 12), and two did not highlight this issue (10, 13). two studies did not mention the loss of samples (12, 13), and another two had low risk of bias (6, 10). also, the study results were correctly reported, and the tools used to measure them were appropriate. in one study, the sample size was found insufficient, and therefore it was considered this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. emami zeydi et al. 4 table 2: basic characteristics of the studies included in the systematic review and meta-analysis first author/year design patient types no. patients no. patients in the intervention group no. patients in the control group type of control/ intervention m/f ratio age (mean± sd) mortality (t/i/c) duration of icu admission (i/c) (mean± sd) vap incidence t/i/c key results chua et al., 2004 (12) philippine rct mechanicallyventilated intubated icu patients 42 22 20 placebo/ 1% pi 40.48/ 59.52 53.00 (sd=16.22) 52.38/ 54.54/50 n/a 33.33/ 27.27/40 no significant effect on vap amd mortality rate, and length of icu stay (p>0.05). seguin et al., 2006 (10) france rct head trauma 98 36 62 saline group (n=31) placebo group (n=31)/pi 10%. 76.53/ 23.47 39.00 (sd=17.00) 22.45/ 16.67/ 32.26/ 19.35 15.00 (sd=14.00)/ 14.00 (sd=12.00)/ 19.00 (sd=15.00) 28.57/ 8.33/ 40.32 significant effect on the prevention of vap (p<0.05). no significant effect on mortality rate and length of icu stays (p>0.05) gupta et al., 2014 (13) india rct mechanicallyventilated intubated icu patients 70 35 35 chlorhexidine /pi 57.14/ 42.86 48.28 (sd=11.14) n/a n/a 14.29/ 17.14/ 11.43 pi was more effective than chlorhexidine in prevention of vap, but the difference was not significant (p>0.05). seguin et al., 2014 (6) france rct severely brain-injured or cerebral hemorrhage patients 167 85 82 placebo/pi 10% 74.25/ 25.75 48.00 (sd=18.50) 29.34/ 32.94/ 25.61 15.00 (sd=13.00)/ 16.00 (sd=14.00) 29.33/ 30.77/ 27.78 no significant effect on on vap amd mortality rate, and length of icu stay (p>0.05). t/i/c: total/intervention/control; pi: povidone-iodine; vap: ventilator-associated pneumonia; rct: randomized clinical trial; icu: intensive care unit; n/a: not available; sd: standard deviation. to have a high risk of bias (12) (figure 2). 3.4. treatment outcome a total of four studies (6, 10, 12, 13) were included in the meta-analysis. in three studies, the effect of pi was compared with the placebo group and, in one study, with chlorhexidine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e31 figure 1: flow diagram of study selection. figure 2: risk of bias based on version 2 of the cochrane risk-of-bias tool for randomized trials (rob 2). the results of the sub-group analysis showed that using pi intervention reduced the incidence of vap, but it was not statistically significant (rr: 0.61, 95% ci: 0.25 to 1.47, z=1.10, p=0.27, i2: 71.5%). also, in one study, the incidence of vap in the pi group was higher than in the chlorhexidine group. however, this difference was not statistically significant (rr: 1.50, 95% ci: 0.46 to 4.87, z=0.67, p=0.50, i2: 0). in general, pi intervention decreased the rate of vap when compared with placebo and chlorhexidine interventions, but it was not statistically significant (rr: 0.74, 95% ci: 0.36 to 1.51, z=0.82, p= 0.41, i2: 62%) (figure 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. emami zeydi et al. 6 figure 3: forest plot for pooled risk ratios regarding povidone-iodine (pi) regimen compared to chlorhexidine and placebo groups on incidence of ventilator-associated pneumonia (vap). ci: confidence interval. figure 4: forest plot for pooled weighted mean difference (wmd) of length of stay in the intensive care unit (day) regarding povidone-iodine (pi) regimen compared to placebo. ci: confidence interval. 3.5. length of icu stay and mortality the results of two studies showed that using pi intervention compared to placebo reduced the average length of stay in icu; however, it was not statistically significant (wmd: -0.35, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e31 figure 5: forest plot for pooled risk ratio of mortality regarding povidone-iodine (pi) regimen compared to placebo. ci: confidence interval; es: effect size. figure 6: funnel plot of publication bias. 95%ci:-3.90 to 3.20, z=0.19, p=0.85, i2: 0) (figure 4). the results of three studies showed that pi intervention compared to placebo had almost same effect on the incidence of mortality (rr: 1.05, 95% ci: 0.66 to 1.53, z=0.8, p=0.27, i2: 29.0%) (figure 5). 3.6. sensitivity analysis sensitivity analysis showed that the overall effect size regarding the effect of pi intervention compared to placebo on vap did not depend on a single study (ci: -2.27 to 0.98). 3.7. publication bias cochrane guidelines did not recommend assessing the publication bias if the number of studies included in the metaanalysis was less than ten. however, the publication bias assessment was performed in the current study. based on the visual inspection of the funnel plot, we found an asymmetry; however, when we did the begg (p= 0.30) and egger’s regression tests (p= 0.19), no significant publication bias was seen for the effects of pi intervention on vap compared to placebo (figure 6). 4. discussion nosocomial infection preventive measures for patients in icu with mechanical ventilation can be divided into two categories: prevention of vap by controlling the aspiration of infected oropharyngeal secretions into the lower respiratory tract and reduction of bacteria that cause vap. one of the most important factors in the occurrence of vap is the aspiration of oropharyngeal fluid containing pathogenic microorganisms. therefore, researchers have tried to reduce the risk of developing vap through oral care (17), showing that the incidence of vap can be reduced through oral care with pi and chlorhexidine (18-21). the present systematic review and meta-analysis assessed the effect of oral care with pi in preventing vap, improving the length of icu stay, and on the mortality rate among mechanically-ventilated icu patients. this systematic review and meta-analysis indicated that the use of pi decreased this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. emami zeydi et al. 8 vap incidence and the average length of icu stay compared to the placebo group. however, these differences were not statistically significant. results showed that the use of pi had an effect similar to the placebo group on the mortality rate. a study in france showed that pi does not affect the incidence of vap and length of stay in the icu (6). however, another study in france showed that the use of pi significantly prevents vap (10). to justify this difference in studies, we can point to the differences in the study population and the type and nature of the underlying diseases that can affect the risk of vap. on the other hand, the results of a systematic review and meta-analysis to evaluate the efficacy of different solutions for oral care in preventing vap showed that due to the high probability of bias in studies, more investigations are needed to provide additional empirical information (21). in addition, some studies have assessed combined oral care interventions for vap prevention. a study in japan found that using a pi gargle swab, brushing teeth, and irrigating with 300 ml of acidic water reduced the risk of vap among mechanically ventilated patients (17). also, the results of a meta-analysis showed that brushing with pi and fluorouracil are the best interventions for preventing vap (21). however, this systematic review and meta-analysis indicated that pi decreased vap incidence and average length of icu stay compared to the placebo group. however, these differences were not statistically significant. also, results showed that pi had an effect similar to placebo on the mortality rate. some causes of similar effect on mortality can be attributed to the insignificant effect of the pi on the mentioned outcomes, such as the concentration of pi used in the studies and the limited capacity to remain chemically active on tissues long after its administration (6). the cdc guidelines recommend the use of iodine before wound closure during surgery. however, it is not recommended as routine care in critically ill patients in icu. in some countries, such as japan, chlorhexidine use is limited because of reports of anaphylactic shock; pi was proposed as a substitute substance. pi has some adverse effects, such as cytotoxic effects, so prolonged use was not recommended. the studies included in this review did not report adverse effects related to pi use; however, more studies are recommended to explore this (8). therefore, further well-designed randomized clinical trials are required to evaluate the potential efficacy of oral care using pi to prevent vap in icu-ventilated patients. 5. limitations a major limitation of the present meta-analysis was the limited number of studies and the geographical dispersion, which makes the generalizability of the findings of this study difficult. future rcts might influence the outcomes of this meta-analysis, with more studies included. 6. conclusion in conclusion, this meta-analysis showed that using pi decreased vap incidence and average length of stay in icu for adult patients admitted to the icu with mechanical ventilation. the use of pi did not reduce the mortality compared to the placebo group. however, these differences were not statistically significant. more rigorously designed rcts and more evidence are required to make a better decision about using pi as a suitable protocol for preventing vap among adult patients admitted to the icu. 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest the authors declare no conflict of interest. 7.3. fundings and supports none. 7.4. authors’ contribution study concept and design by all authors; data acquisition by all authors; data interpretation by all authors; drafting of the manuscript by all authors; revision of the manuscript by all authors; the final version of the manuscript is approved by all authors. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. references 1. papazian l, klompas m, luyt c-e. ventilator-associated pneumonia in adults: a narrative review. intensive care med. 2020;46(5):888-906. 2. zhao t, wu x, zhang q, li c, worthington hv, hua f. oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. cochrane database syst rev. 2020;12:1-139. 3. spalding mc, cripps mw, minshall ct. ventilatorassociated pneumonia: new definitions. crit care clin. 2017;33(2):277. 4. oliveira j, zagalo c, cavaco-silva p. prevention of ventilator-associated pneumonia. rev port pneumol. 2014;20(3):152-61. 5. satheeshkumar ps, papatheodorou s, sonis s. enhanced oral hygiene interventions as a risk mitigation strategy this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e31 for the prevention of non-ventilator-associated pneumonia: a systematic review and meta-analysis. br dent j. 2020;228(8):615-22. 6. seguin p, laviolle b, dahyot-fizelier c, dumont r, veber b, gergaud s, et al. effect of 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a. gray literature: an important resource in systematic reviews. j evid based med. 2017;10(3):233-40. 16. sterne ja, savović j, page mj, elbers rg, blencowe ns, boutron i, et al. rob 2: a revised tool for assessing risk of bias in randomised trials. bmj. 2019;366. 17. mori h, hirasawa h, oda s, shiga h, matsuda k, nakamura m. oral care reduces incidence of ventilatorassociated pneumonia in icu populations. intensive care med. 2006;32(2):230-6. 18. khezri hd, zeydi ae, firouzian a, baradari ag, mahmoodi g, kiabi fh, et al. the importance of oral hygiene in prevention of ventilator-associated pneumonia (vap): a literature review. int j caring sci. 2014;7(1):12-23. 19. klarin b, adolfsson a, torstensson a, larsson a. can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? a multicentre, prospective, randomised controlled open trial. crit care. 2018;22(1):1-10. 20. akbiyik a, hepçivici z, eşer i, uyar m, çetin p. the effect of oropharyngeal aspiration before position change on reducing the incidence of ventilator-associated pneumonia. eur j clin microbiol infect dis. 2021;40(3):615-22. 21. sankaran sp, sonis s. network meta-analysis from a pairwise meta-analysis design: to assess the comparative effectiveness of oral care interventions in preventing ventilator-associated pneumonia in critically ill patients. clin oral investig. 2021:1-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e46 or i g i n a l re s e a rc h comparing two naloxone tapering methods in management of methadone intoxication; a quasi-experimental study mohammad javad zarei1, maral ramezani2,3, zahra sahraie4, shahin shadnia5, peyman erfan talab evini5, babak mostafazadeh5, mitra rahimi5∗ 1. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of pharmacology, school of medicine, arak university of medical sciences, arak, iran. 3. traditional and complementary medicine research center, arak university of medical sciences, arak, iran. 4. department of clinical pharmacy, faculty of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 5. toxicological research center, excellence center & department of clinical toxicology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. received: april 2023; accepted: may 2023; published online: 15 june 2023 abstract: introduction: even though naloxone is the main treatment for methadone poisoning treatment there are controversies about the proper method of its tapering. this study aimed to compare two methods in this regard. methods: this study was a prospective, single-blind pilot quasi-experimental study on non-addicted adult patients poisoned with methadone. patients were randomly divided into 2 groups. in one group, after stabilization of respiratory conditions and consciousness, naloxone was tapered using the half-life of methadone and in the other group, naloxone was tapered using the half-life of naloxone. recurrence of symptoms and changes in venous blood gas parameters were compared between groups as outcome. results: 52 patients were included (51.92% female). 31 cases entered group a (tapering based on methadone’s half-life) and 21 cases entered group b (tapering based on naloxone’s half-life). the two groups were similar regarding mean age (p = 0.575), gender distribution (p = 0.535), the cause of methadone use (p = 0.599), previous medical history (p = 0.529), previous methadone use (p = 0.654), drug use history (p = 0.444), and vital signs on arrival to emergency department (p = 0.054). the cases of re-decreasing consciousness during tapering (52.38% vs. 25.81%; p = 0.049) and after discontinuation of naloxone (72.73% vs. 37.50%; p = 0.050) were higher in the tapering based on naloxone half-life group. the relative risk reduction (rrr) for naloxone half-life group was -1.03 and for methadone half-life group was 0.51. the absolute risk reduction (arr) was 0.27 (95% confidence interval (ci) = 0.01-0.53) and the number needed to treat (nnt) was 3.7 (95% ci= 1.87150.53). there was not any statistically significant difference between groups regarding ph, hco3 , and pco2 changes during tapering and after naloxone discontinuation (p > 0.05). however, repeated measures analysis of variance (anova), showed that in the tapering based on methadone’s half-life group, the number of changes and stability in the normal range were better (p < 0.001). conclusion: it seems that, by tapering naloxone based on methadone’s half-life, not only blood acid-base disorders are treated, but they also remain stable after discontinuation and the possibility of symptom recurrence is reduced. keywords: naloxone; methadone; drug users; poisoning; drug tapering cite this article as: zarei mj, ramezani m, sahraie z, shadnia s, talab evini pe, mostafazadeh b, rahimi m. comparing two naloxone tapering methods in management of methadone intoxication; a quasi-experimental study. arch acad emerg med. 2023; 11(1): e46. https://doi.org/10.22037/aaem.v11i1.2047. ∗corresponding author: mitra rahimi; toxicological research center, excellence center & department of clinical toxicology, loghman hakim hospital, tehran, iran. email: mrahimi744@gmail.com, orcid: https://orcid.org/00000002-8785-8207. 1. introduction methadone is a synthetic opioid substance that was developed in the 1940s as a pain reliever. this drug is the most widely used treatment for opioid dependence and has been used worldwide for more than 40 years under the name methadone maintenance treatment (mmt)(1). previous studies have shown that mmt reduces the risk of crime, illicit this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mj. zarei et al. 2 drug use, morbidity, and mortality, and improves behaviors in patients compared to opioid users (2-4). methadone toxicity is rising among those accidentally exposed to it, which results in increased mortality. methadone intoxication results in clinical manifestations such as loss of consciousness, respiratory depression (bradypnea/apnea), cardiovascular disturbances (hypotension, cardiac arrhythmia, and qt prolongation), nausea, vomiting, seizures, and miosis. the duration of intoxication with methadone is long compared to other opioid substances (5-7). the most widely used antidote in acute opioid poisoning is the administration of naloxone(8-10). pharmacologically, naloxone is a pure opioid receptor antagonist. by a competitive mechanism, it blocks the binding of opioid substances to the receptor. after initiation, naloxone is tapered based on the patient’s condition and subsequently discontinued. if naloxone is administered in high doses or repeat doses are administered too rapidly, naloxone can precipitate acute opioid withdrawal syndrome. signs of this syndrome include vomiting, tachycardia, shivering, sweating, and tremor (11). serious adverse effects can include pulmonary edema, hypertensive emergencies, ventricular dysrhythmias, delirium, seizures, and death (11-15). even if an immediate, lifethreatening adverse event does not occur, patients with acute opioid withdrawal are agitated and usually require sedative drugs, putting them at risk for aspiration, and recurrent respiratory depression (11). despite the seriousness of methadone poisoning, there are no specific recommendations in medical textbooks for how to administer naloxone. naloxone is accepted as a first-line antidote, in some sources as a prn (pro re nata) regimen, and as a continuous intravenous infusion. the length of treatment and its dosage is unknown. 12 to 18 hours, 0.25-6.25 mg/h up to 25 mcg/kg/h is recommended (16-18). on the other hand, there is no discussion about how to taper naloxone after the patient’s condition is stable. this is a dilemma in clinical toxicology. trying to find a safer method in this regard, this study aimed to compare tapering based on naloxone half-life and based on methadone halflife for treatment of methadone intoxicated patients in emergency department. 2. methods 2.1. study design and setting this study was a prospective, single-blind, and pilot quasiexperimental study, which was conducted on non-addicted patients poisoned with methadone who were referred to loghman hakim hospital, tehran, iran, during 2021-2022. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences with the code ir.sbmu.retech.rec.1400.1038. participants signed informed written consent forms. this article was also registered in the iranian registry of clinical trials with number: irct20220305054196n1. 2.2. participants methadone-poisoned patients over 18 years of age, who presented with a reduced level of consciousness with or without respiratory depression, didn’t have an addiction, and were not under mmt treatment were included. patients with methadone poisoning with other hypnotic sedatives, patients who were discharged against medical advice, and patients who experienced withdrawal syndrome symptoms after receiving naloxone or did not need naloxone were excluded from the study. 2.3. data gathering methadone poisoning was confirmed by history and urine drug tests. the patient’s addiction history was recorded based on the information given by the patient or his/her companions. concomitant poisoning was diagnosed using symptoms, history, and results of urine tests. upon arrival, vital signs (blood pressure, heart rate, breathing rate, body temperature, level of consciousness, and percentage of oxygen saturation) were recorded and a blood sample was collected for venous blood gas (vbg) analysis. the amount of methadone consumed was recorded. then the patients were treated with naloxone. ph, pco2 (partial pressure of carbon dioxide), and hco3 (bicarbonate) concentrations were recorded before starting tapering, during tapering, and after discontinuation of naloxone. the time of improvement of symptoms (reaching the percentage of oxygen saturation above 90%), return of consciousness (patient being awake and aware of surroundings and identity), and resolution of respiratory depression was recorded. the final condition of the patient was checked. the endpoint of tapering was the amount of naloxone administered being less than 0.1 mg/hour and the stability of the pco2 level and the patient’s consciousness. 2.4. intervention patients were allocated to the groups based on random numbers table. patients were clinically evaluated without knowing which method was used for naloxone tapering. in one group, after the patient’s condition was stable, naloxone was tapered using the half-life of naloxone (decreasing the dose of naloxone by 50% every 3 hours), and in the other group, naloxone was tapered using the half-life of methadone (decreasing the dose of administered naloxone by 50% every 6 hours). after discontinuation of naloxone, patients were monitored for 8 hours. tapering methods were designed based on the relative estimation of the half-life of naloxone this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e46 and methadone, as well as the experiences of researchers in clinical treatment. 2.5. outcomes time to recovery, the re-decreasing consciousness, and change in vbg parameters (ph, hco3, and pco2) during tapering and after discontinue of naloxone were compared between groups as outcome. 2.6. statistical analysis considering 95% confidence interval and alpha error of 5%, the sample size was considered to be 50 cases. spss software version 21 was used to analyze the information. the population normality was assessed using kolmogorov-smirnov test, then independent and paired t-test were used for parametric data and chi-square for non-parametric data. p<0.05 was considered as the level of significance. regression models were used for controlling confounding variables. 3. results 3.1. baseline characteristics of studied cases 52 patients were included, 27 (51.92%) were female and 25 (48.07%) were male. 31 cases entered group a (tapering based on the methadone half-life) and 21 cases entered group b (tapering based on the naloxone half-life). most of the patients (61.54%) had taken methadone due to suicide, and had no history of illness and drug or methadone use. six people had a history of suicide attempts with methadone (4 people in group a and 2 people in group b). table 1 compares the baseline characteristics of studied patients between groups. the mean age of the patients was 28.68±10.9 years in group a, and 28.38±11.5 years in group b (p = 0.575). there was no difference between the two groups regarding gender distribution (p = 0.535), cause of methadone use (p = 0.599), previous medical history (p = 0.529), previous methadone use (p = 0.654), drug use history (p = 0.444), and vital signs on arrival to emergency department (p = 0.045). none of the patients needed intubation. although all patients were candidates for admission to intensive care unit (icu), only 3 patients were treated in icu. all patients recovered and were discharged from the hospital. 3.2. comparing the outcomes table 2 and figure 1 compare the studied outcomes between the two groups. the cases of re-decreasing consciousness during tapering (52.38% vs. 25.81%; p = 0.049) and after discontinue naloxone (72.73% vs. 37.50%; p = 0.050) were higher in the tapering based on naloxone half-life group. the relative risk of re-decreasing of consciousness during tapering was 0.49 and 2.03 in methadone half-life and naloxone halflife groups, respectively. the relative risk reduction (rrr) figure 1: comparing the ph, hco3 , and pco2 changes in the patients poisoned with methadone between the two groups of naloxone tapering based on methadone half-life and naloxone half-life. was -1.03 for naloxone half-life group and 0.51for methadone half-life group. the absolute risk reduction (arr) was 0.27 (95% ci = 0.01-0.53) and the number needed to treat (nnt) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mj. zarei et al. 4 table 1: comparing the baseline characteristics of studied cases between the two groups variable tapering based on the half-life of p-value methadone (n = 31) naloxone (n = 21) gender male 16 (51.6) 9 (42.9) 0.535 female 15 (48.4) 12 (57.1) age (years) mean ± sd 28.7±11.0 28.4±11.5 0.575 consumption due to suicide attempt yes 20 (64.5) 12 (57.1) 0.599 medical history previous use of methadone 6 (19.3) 2 (9.5) 0.654 previous disease 3 (9.7) 2 (9.5) 0.529 drug use 6 (19.3) 4 (19.1) 0.444 smoking 8 (25.8) 6 (28.6) 0.684 alcohol consumption 1 (3.2) 0 (0.0) marijuana consumption 2 (6.4) 0 (0.0) taking psychotropic pills 2 (6.4) 1 (4.8) vital signs systolic bp (mmhg) 112.6±13.6 109.8±8.5 0.054 diastolic bp (mmhg) 74.1±13.1 71±7.5 0.054 pr (pulses/ minute) 90.93±16.5 80.11±22.06 0.65 rr (breaths/ minute) 17.8±7.8 15.87±2.8 0.173 glasgow coma scale 12.7±2.3 12.3±2.7 0.289 o2 saturation (%) 86.6±14.2 87±19.3 0.393 treatment in icu yes 1 (3.2) 2 (9.5) 0.339 naloxone dose (mg) loading 1.97±1.4 1.28±0.7 0.067 maintenance 1.07±0.64 0.81±0.37 0.073 vbg findings primary ph 7.26±0.09 7.27±0.09 0.558 primary hco3 23.87±5.7 25.84±3.6 0.187 primary pco2 (mmhg) 56.63±15.4 55.69±11.2 0.162 data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure, icu: intensive care unit, pr: pulse rate, rr: respiratory rate, vbg: venous blood gas. was 3.7 (95% ci= 1.87150.53). there was not any statistically significant difference between groups regarding ph, hco3, and pco2 changes during tapering and after naloxone discontinuation (p > 0.05). however, repeated measures anova, shows that in the tapering with methadone half-life group, the number of changes and stability in the normal range were better (p < 0.001). 4. discussion we found that although the recovery time of decreased consciousness was not significantly different in the two methods, the return of central nervous system (cns) depression during dose reduction was significantly different. in patients tapered based on half-live of naloxone, the number of cases with re-decreasing cns depression was higher than the other group and this re-decreasing occurred most significantly in time of discontinuing naloxone. the number of changes in ph, hco3 and pco2 in the group tapering based on the methadone half-life was better during dose reduction and after naloxone discontinuation. methadone is a synthetic opium that is used as a pain reliever and in the maintenance treatment of addicted patients, and its consumption is increasing (19). accidental use or overdose of methadone can cause multiple organ damage in both humans and animals (20-22). methadone has significant tissue distribution; tissue levels may exceed plasma levels. the lipophilic nature of methadone allows for rapid absorption, long duration of action, and slow release from tissues into the bloodstream. this causes wide variations in the half-life, giving a range of 2 to 65 hours (23). opioid and methadone overdose syndrome is a true medical emergency. naloxone is mainly administered intravenously at the same time as other supportive measures (24, 25). naloxone has a rapid onset of action, its maximum serum concentration is reached 2 minutes after intravenous injecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e46 table 2: comparing the outcomes of studied cases between groups outcomes tapering based on the half-life of p-value methadone (n = 31) naloxone (n = 21) ph during tapering 7.36±0.03 7.36±0.03 0.738 after discontinuing naloxone 7.37±0.04 7.35±0.05 0.239 hco3 (mmhg) during tapering 26.47±3.6 27±3.4 0.684 after discontinuing naloxone 27.28±4.9 28.35±2.8 0.050 pco2 (mmhg) during tapering 45.9±10.4 46.8±4.2 0.074 after discontinuing naloxone 49.6±11.01 51.3±7.8 0.318 re-decreased consciousness during tapering 8 (25.81) 11 (52.38) 0.049 after discontinuing naloxone 3 (37.5) 8 (72.73) 0.050 time to recovery (day) from respiratory depression 0.29±0.5 0.43±0.5 0.085 final outcome recovery 31 (100.0) 21 (100.0) 0.596 data are presented as mean ± standard deviation (sd) or frequency (%). the blood gas analysis is reported based on venous sample. tion, 10 minutes after intramuscular injection, and 15 to 30 minutes after intranasal administration (26). naloxone is extensively metabolized in the liver, its serum half-life is about 30 to 90 minutes (27). although naloxone is relatively safe in naïve persons, it should be used with caution in chronic methadone users who experience overdose. high blood levels of naloxone can trigger drug withdrawal symptoms in people who have previously been exposed to methadone. the onset of withdrawal symptoms can increase an individual’s risk of relapse (28, 29). we conducted this study on non-addicted subjects to cover this major confounding factor and not have to discontinue naloxone due to withdrawal syndrome. unfortunately, none of the studies have worked on the tapering method. given that naloxone has a much shorter halflife than methadone (90 minutes vs. 65 hours), re-depression of the cns may occur due to the slow release of methadone from the tissues into the blood after discontinuation of naloxone (23, 30). we observed that in the taper group based on the half-life of naloxone, the cases of re-decreasing consciousness were significantly higher (52.38%) and 72.73% of them showed decreased consciousness after discontinuation of naloxone. this could be due to the patient being naloxonefree when there is still methadone in her/his body and it is slowly released from the storage places and causes brain effects. dr. yazdanbakhsh and his colleagues have conducted a study on the comparison of two naloxone-based regimens in the treatment of methadone overdose. they randomly divided 80 patients with methadone overdose into two groups: the infusion and the prn groups. the severity of deprivation syndrome was evaluated after 30 minutes, 3 hours and 12 hours of treatment in both groups. their results showed that administering naloxone as prn reduces the amount and severity of withdrawal syndrome (31). dr. khosravi et al. conducted a study, comparing two naloxone regimens. 100 opioid-dependent patients with signs/symptoms of methadone overdose were included in the study. patients were allocated to groups treated based on tintinalli protocol (group 1) or goldfrank diet protocol (group 2). group 1 received naloxone at a dose of 0.1 mg every two to three minutes, while group 2 received naloxone at an initial dose of 0.04 mg, which was increased to 0.4, 2, and 10 mg every two to three minutes until respiratory depression was reversed. they then compared them in terms of reversal of toxicity and risk of complications. finally, their results showed that the gradual titration of naloxone with the tintinalli protocol can reduce major complications compared to the goldfrank regimen (32). neither of the two studies discussed the issue of naloxone tapering. it may seem that the gradual discontinuation of naloxone based on the half-life of naloxone reduces the length of stay in the hospital and the overall cost of the patient, but our results showed that firstly, there was no significant difference in icu admission, the initial dose of naloxone, and the maintenance dose between the two groups. the risk of re-reducing consciousness was higher in the group tapered based on the half-life of naloxone. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mj. zarei et al. 6 5. limitations the limitations of this study were the small number of patients in each group, the lack of equality of patients in the two groups, the failure to examine the trend of all clinical factors and symptoms in the two groups, and the lack of blinding of the main investigators during the study. 6. conclusion it seems that, by tapering naloxone based on methadone’s half-life, not only blood acid-base disorders are treated, but they also remain stable after discontinuation and the possibility of symptom recurrence is reduced. 7. declarations 7.1. acknowledgments the authors would like to thank the toxicological research center (trc) of loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran for their support, cooperation, and assistance throughout the study. the researchers also thank and appreciate the support of professor latif gachkar in the design and implementation of this research. 7.2. conflict of interest we declare that we have no conflicts of interest. 7.3. funding and support toxicological research center (trc) of loghman hakim hospital, shahid beheshti university of medical sciences 7.4. authors’ contribution all authors made a significant contribution to the work reported, whether in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. 7.5. availability of data the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. 7.6. using artificial intelligence chatbots none. references 1. joseph h, stancliff s, langrod j. methadone maintenance treatment (mmt): a review of historical and clinical issues. mt sinai j med. 2000;67(5-6):347-64. 2. clausen t, anchersen k, waal h. mortality prior to, during and after opioid maintenance treatment (omt): a national prospective cross-registry study. drug alcohol depend. 2008;94(1-3):151-7. 3. bell j, zador d. a risk-benefit analysis of methadone maintenance treatment. drug saf. 2000;22(3):179-90. 4. marsch la. the efficacy of methadone maintenance 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side effects of two naloxone-based regimens in treatment of methadone overdose. ijt. 2016;10(1):49-52. 32. khosravi n, zamani n, hassanian-moghaddam h, ostadi a, rahimi m, kabir a. comparison of two naloxone regimens in opioid-dependent methadone-overdosed patients: a clinical trial study. curr clin pharmacol. 2017;12(4):259-65. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e40 or i g i n a l re s e a rc h dental students’ perceptions regarding bioterrorism; a cross-sectional study lina bahanan1∗, maha alsharif2, omar al qhtani3, ahmad al juhani3, meyassara samman1 1. department of dental public health, king abdulaziz university, faculty of dentistry, jeddah, saudi arabia. 2. department of oral diagnostic sciences, king abdulaziz university, faculty of dentistry, jeddah, saudi arabia. 3. king abdulaziz university, faculty of dentistry, jeddah, saudi arabia. received: march 2023; accepted: april 2023; published online: 22 may 2023 abstract: introduction: during the covid-19 outbreak, dental professionals have demonstrated their importance in combating mass casualty incidents. this study aimed to understand dental students’ perceptions of their potential roles in a bioterrorism attack. methods: this cross-sectional study used a self-administered anonymous questionnaire, which was sent to all dental students and interns at king abdulaziz university, saudi arabia. bivariate and multiple linear regression analyses were conducted to assess dental students’ willingness to provide care during a bioterrorism attack, knowledge regarding bioterrorism and total number of roles a dentist should play during an attack. results: this study included 472 dental students and interns. the mean knowledge score regarding bioterrorism was 3.3 ± 1.9 out of 5. a large majority of the respondents (83.8%) were willing to provide care during a bioterrorism attack. students with a cumulative grade point average (gpa) of 4.5–5 were more likely to indicate that a dental professional should take on more roles during a bioterrorism attack than those with a gpa of 2.5–2.99. fourthand fifth-year dental students had lower knowledge scores regarding bioterrorism than dental interns (b: -0.71; se: 0.30; 95% ci: -1.3—0.1 and b: -0.68; se: 0.30; 95% ci: -1.3– -0.1, respectively). conclusion: despite the fact that dental curricula do not cover topics related to bioterrorism, most students would be willing to provide care under bioterrorism conditions. there is wide agreement among the students regarding the need to add bioterrorism-related educations to dental curricula. keywords: covid-19; dentistry; disaster planning; education, dental cite this article as: bahanan l, alsharif m, al qhtani o, al juhani a, samman m. dental students’ perceptions regarding bioterrorism; a cross-sectional study. arch acad emerg med. 2023; 11(1): e40. https://doi.org/10.22037/aaem.v11i1.2018. 1. introduction bioterrorism can be defined as a terrorist attack via a biological agent or the intentional use of a harmful biological agent that causes a civil illness, physical dysfunction or death (1, 2). appropriate interventions must be implemented as soon as a threat is identified to limit the morbidity and mortality caused by the attack (3). with the increased incidence of biological weapon use worldwide, healthcare personnel are an indispensable factor in facing such threats (3). there have been many claims and conspiracy theories that the covid19 global pandemic was a result of deliberate bioterrorism dentists are considered vital members of the healthcare community as they play a significant role in combating ∗corresponding author: lina bahanan; king abdulaziz university, faculty of dentistry, department of dental public health, jeddah, saudi arabia. email: lbahanan@kau.edu.sa. tel: +966126403443, orcid: https://orcid.org/00000001-6508-5939. bioterrorism attacks (4–6). the role of the dental professionals in bioterrorism attacks was defined by the american dental association (ada) in 2002 (7). dentists may be called upon to fill a range of roles in the event of a bioterrorism attack, including but not limited to education, sample collection, diagnosis, providing first aid and cardiopulmonary resuscitation (cpr), starting iv lines, suturing, vaccination, distribution of medications, and decontamination (7,8). the role of dentists in the covid-19 outbreak has revealed their importance in combating any mass casualty incident that may arise from natural or human-caused circumstances. licensed dental professionals were able to perform nasopharyngeal and oropharyngeal swabs for covid-19 diagnoses (8). moreover, covid-19 screening capacity was increased through the use of dental clinics with negative pressure and high-volume excavators (8). it is, therefore, important for dental schools to expand their curricula to include preparedness skills for pandemics and natural catastrophes (8). dental personnel, however, may face challenges during this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index l. bahanan et al. 2 bioterrorist attacks due to a lack of knowledge and experience (4). a study by bhoopathi et al. revealed that dentists both exposed and unexposed to a bioterrorism event showed low levels of perceived bioterrorism attack preparedness (9). another study showed that less than 15% of dentists were able to identify a bioterrorism event, and less than 10% were confident that they could respond effectively in a bioterrorist attack (10). to lower morbidity and improve outcomes during such malicious events, dental schools should incorporate pandemic and disaster preparedness skills into their curricula. moreover, this would allow dental students to recognise and effectively respond to any catastrophic event and bioterrorist attack (8,11.) thus, this study aimed to understand dental students’ perceptions of their potential roles in a bioterrorism attack, self-perceived knowledge and selfperceived need for education. 2. methods 2.1. study design and setting this cross-sectional study was conducted between september 2021 and may 2022, with participants recruited between november 2021 and january 2022 using a self-administered anonymous questionnaire regarding the students’ perceptions about bioterrorism attack, which was sent to all dental students and interns at king abdulaziz university, saudi arabia. the study was reviewed and approved by the institutional review board at king abdulaziz university faculty of dentistry (#364-12-21). all participants provided informed consent. this study was performed in accordance with the principles of the declaration of helsinki. 2.2. study participants the inclusion criteria for the study included undergraduate dental students (second through sixth year) and dental interns at king abdulaziz university faculty of dentistry. sample size calculation was performed using raosoft sample size calculator with a population size of 861 students and interns, response distribution of 50%, confidence level of 95% and error margin of 5% (12). this study required a minimum sample size of 266 participants. 2.3. data gathering a self-administered anonymous questionnaire was adapted from previous studies (9,13–15). to ensure the validity and reliability of the questionnaire, it was evaluated by two academic dentists. in addition, a pilot test was conducted on 12 participants from the target population (two students from each year). the pilot test aimed to identify any potential issues with the questionnaire, such as vague or confusing questions, and to assess the clarity and comprehensibility of the questionnaire. based on the results of the pilot test, the questionnaire was modified and finalized for use in the main data collection. moreover, the internal consistency and reliability of the questionnaire were assessed using cronbach’s alpha coefficient, which was > 0.7 indicating an acceptable level of reliability and consistency. it was distributed in english using question pro forms. every student received an email with the survey link and detailed instructions regarding the study. two reminders were sent, two weeks and one month after the first email. participation was completely voluntary and informed consent was obtained from each participant. the questionnaire consisted of five main sections. the first section comprised personal questions, including on gender (male or female), year of study (second, third, fourth, fifth, sixth, interns), grade point average (gpa) (4.5–5, 4–4.49, 3.5–3.99, 3–3.49, 2.5–2.99 and less than 2.5) and marital status (single or married). the second section included a yes–no question about the students’ willingness to provide care during a bioterrorist attack. it also included 5-point likert scale questions about students’ opinions regarding the following topics: “1) bioterrorism is a national security concern, 2) local community at risk of bioterrorism attack, 3) first responder team should include dental professionals”. in the third section, respondents were asked to choose from 10 potential roles that a dental professional could play during a bioterrorism attack, as recommended by the ada. the fourth section consisted of yes–no questions to assess students’ selfperceived knowledge regarding whether they “1) would be able to identify signs and symptoms of an attack, 2) know who to contact in case of an attack, 3) know how to get information about an attack, 4) know how to get clinical information about a bioterrorism-related disease, 5) know the current state of bioterrorism and how to manage it”. the level of knowledge was then categorised according to the number of affirmative responses (good: 4–5, fair: 3, poor: 0–2). the final section comprised five questions about the selfperceived need for education and training on bioterrorism: ‘1) the need for more education regarding bioterrorism, 2) knowledge of a bioterrorism-related continuing education course, 3) previous training in bioterrorism, 4) incorporating bioterrorism preparedness into dental curricula, 5) willingness to attend a continuing education course on bioterrorism’. the questionnaire is attached as appendix a. omar al qhtani and ahmad al juhani were responsible for data gathering. 2.4. statistical analysis statistical analyses were conducted using the statistical package for the social sciences (spss), version 20. we used cronbach’s alpha to determine the internal consistency of the opinion domain. descriptive statistics, such as frequencies this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e40 table 1: characteristics of studied dental students (n=472) characteristic value gender male 248 (53.0) female 220 (47.0) age (year) mean ± sd 21.6 ± 1.7 year of study 2nd 64 (13.6) 3rd 81 (17.3) 4th 80 (17.1) 5th 85 (18.1) 6th 73 (15.6) dental intern 86 (18.3) cumulative gpa 4.5-5 188 (40.1) 4-4.49 207 (44.1) 3.5-3.99 58 (12.4) 3-3.49 12 (2.6) 2.5-2.99 4 (0.9) marital status single 457 (98.9) married 5 (1.1) willing to provide care yes 393 (83.8) no 76 (16.2) total score of self-perceived knowledge (out of 5) mean ± sd 3.3±1.9 total number of roles during a bioterrorism attack (out of 10) mean ± sd 8.3±2.4 data are presented as mean ± standard deviation (sd) or frequency (%). some variables do not add up to the total, as not all participants answered every question. gpa: grade point average. and percentages, were used to report the sample characteristics. bivariate analysis was used to assess students’ opinions and self-perceived need for education against the sample characteristics. using a multivariate linear regression analysis, the dependent variable dental students’ need for bioterrorism education and training was determined based on the following predictors: gender, year of study, gpa, and marital status. we chose to handle the missing data using the pairwise deletion method, which involves excluding cases with missing data on a particular variable from the analysis for that variable only. the significance level was set at p < 0.05. 3. results a total of 472 participants with the mean age of 21.6 ± 1.7 (range: 19 24) years were included in the study, which corresponds to a response rate of 54.8%. the response rate may indicate that students were overburdened with requirements and exams or that awareness of the topic was partially underdeveloped. more than half of the respondents were male (53.0%). the majority of participants were single (98.9%), had a cumulative gpa ≥ 4 (84.2%) and were willing to provide care during a bioterrorist attack (83.8%) (figure 1). the mean total score of self-perceived knowledge regarding bioterrorism was 3.3 ± 1.9 out of 5. moreover, the mean total number of roles that participants perceived that a dentist should play during a bioterrorism attack was 8.3 ± 2.4 out of 10 (table 1). table 2 shows students’ perceptions regarding bioterrorism preparedness and management. most of the respondents (78.2%) believed that bioterrorism is a national concern, and a substantial majority (71.7%) believed that the local community is at risk of bioterrorism. additionally, 68.6% of the participants believed that one of the first responder teams should be dental professionals. most of the responders agreed with the roles given by the ada regarding bioterrorism, with the majority believing they should provide first aid and cpr (90.5%) and a smaller majority considering that they should diagnose a possible bioterrorist attack (76.4%). according to 75.2% of the respondents, the dental curriculum should include bioterrorism, and 76.3% were willing to attend a continuing education course on the topic (figure 1). overall, participants showed willingness to provide care during a bioterrorism event, though none of the results were statistically significant. females (85.9%) showed slightly more willingness than males (82.1%). dental interns were the most willing to provide care (88.1%), and students in the fifth year were the least willing to provide it (81.2%). respondents with a gpa of 3–3.49 were the most willing to provide care (91.7%). single dental students (84%) were slightly more likely to provide care than married dental students (80%) (table 3). most participants from both genders (males 71.4% and females 75.8%) had excellent knowledge of bioterrorism. there was also an almost equal gender distribution of poor knowledge (males 8.2% and females 9.0%). dental interns had the highest proportion of excellent knowledge regarding bioterrorism (83.9%), whereas secondand fourth-year dental students had the highest proportion of poor knowledge regarding bioterrorism (13.1% and 13.3%, respectively) (table 4). a linear regression model to predict the score of knowledge regarding bioterrorism and the number of roles that a dentist should play during a bioterrorism attack included the following: gender, year of study, cumulative gpa, and marital status (table 5). according to our findings, fourthand fifth-year dental students had significantly less knowledge of bioterrorism than dental interns. furthermore, dental interns reported a significantly higher number of roles that a dental professional should play during a bioterrorism attack than dental students from the second to fifth years. moreover, participants with a cumulative gpa of 4.5–5 and 4–4.49 were significantly more likely to indicate that a dental professional should take on more roles during a bioterrorism attack than those with a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index l. bahanan et al. 4 table 2: students’ perception regarding bioterrorism preparedness and management variable of interest number (%) students’ opinion regarding bioterrorism (affirmative response) bioterrorism is a national security concern 366 (78.2) local community at risk of bioterrorism attack 324 (71.7) first responder team should include dental professionals 310 (68.6) students’ perception regarding the roles during a bioterrorism event (affirmative response) report a possible bioterrorism infection 394 (85.7) identify and triage victims 373 (81.8) provide information and guidance to the public during an attack 384 (82.9) diagnose a possible bioterrorism infection 350 (76.4) keep dental records for forensic identification 402 (87.2) provide first aid and cardiopulmonary resuscitation 420 (90.5) perform forensic dentistry 380 (82.1) provide assistance to medical personnel (e.g., physician, nurse) 388 (84.2) create an alternative medical site by providing clinic space 403 (86.7) give vaccines and medications under supervision 405 (87.7) table 3: bivariate analysis of demographic characteristics and willing to provide care during a bioterrorism attack characteristic willing to provide care during a bioterrorism attack p-value yes n (%) no n (%) gender male 202 (82.1) 44 (17.9) 0.3 female 189 (85.9) 31 (14.1) year of study 2nd 53 (82.8) 11 (17.2) 3rd 66 (81.5) 15 (18.5) 4th 68 (85.0) 12 (15.0) 0.8 5th 69 (81.2) 16 (18.8) 6th 61 (83.6) 12 (16.4) dental intern 74 (88.1) 10 (11.9) cumulative gpa 4.5-5 156 (83.0) 32 (17.0) 4-4.49 176 (85.0) 31 (15.0) 3.5-3.99 46 (82.1) 10 (17.9) 0.8 3-3.49 11 (91.7) 1 (8.3) 2.5-2.99 3 (75.0) 1 (25.0) marital status single 382 (84.0) 73 (16.0) 0.6 married 4 (80.0) 1 (20.0) data are presented as frequency (%). gpa: grade point average. gpa of 2.5–2.99 (table 5). 4. discussion the purpose of this cross-sectional study was to examine dental students’ perceptions of their potential roles in a bioterrorism attack, self-perceived knowledge and selfperceived need for education. this study found that dental interns had a higher level of knowledge about bioterrorism than fourthand fifth-year dental students. the majority of dental students believed that dental professionals should be part of the first responder team. furthermore, most dental students were willing to assist during a bioterrorist attack. they also recommended including bioterrorism preparedness in dental curricula. our findings regarding high willingness of dental students and interns to provide care during a bioterrorism attack were in line with those of previous studies. bhatt et al., who evaluated indian students’ knowledge and willingness to assist in a bioterrorist attack, found that 96.6% of undergraduate dental students were willing to provide care during an attack (13). in boston in 2005, the majority (92.0%) of the dental students, assistants and hygienists attending the yankee dental conference expressed willingness to assist during an attack (14). similarly, katz et al. revealed that 73.8% of hawaithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e40 table 4: bivariate analysis of demographic characteristics and level of knowledge regarding bioterrorism characteristic level of knowledge regarding bioterrorism p-value excellent fair poor gender male 105 (71.4) 30 (20.4) 12 (8.2) 0.5† female 100 (75.8) 20 (15.2) 12 (9.0) year of study 2nd 24 (63.2) 9 (23.7) 5 (13.1) 3rd 35 (72.9) 10 (20.8) 3 (6.3) 4th 30 (66.7) 9 (20.0) 6 (13.3) 0.4‡ 5th 32 (69.6) 10 (21.7) 4 (8.7) 6th 36 (78.2) 5 (10.9) 5 (10.9) dental intern 47 (83.9) 7 (12.5) 2 (3.6) cumulative gpa 4.5-5 80 (70.8) 24 (21.2) 9 (8.0) 4-4.49 95 (76.0) 16 (12.8) 14 (11.0) 0.3‡ 3.5-3.99 22 (66.7) 9 (27.3) 2 (6.0) 3-3.49 8 (100.0) 0 (0.0) 0 (0.0) 2.5-2.99 1 (50.0) 1 (50.0) 0 (0.0) marital status single 201 (73.9) 48 (17.7) 23 (8.4) 0.2¥ married 0 (0.0) 1 (100.0) 0 (0.0) data are presented as frequency (%). gpa: grade point average, †chi-square test, ‡fisher exact test with monte carlo simulation, ¥fisher exact test. table 5: linear regression model predicting students’ total knowledge score regarding bioterrorism and total number of roles a dentist should play during a bioterrorism attack total knowledge score total number of roles variables estimate se 95% ci estimate se 95% ci gender male ref ref ref ref ref ref female -0.04 0.19 -0.4 – 0.3 0.09 0.22 -0.4 – 0.5 year of study 2nd -0.51 0.34 -1.2 – 0.2 -1.9 0.40 -2.7 – -1.1* 3rd -0.56 0.30 -1.1 – 0.03 -1.9 0.36 -2.6 – -1.2* 4th 0.71 0.30 -1.3 – -0.1* -1.1 0.36 -1.8 – -0.3* 5th -0.68 0.30 -1.3 – -0.1* -0.9 0.36 -1.6 – -0.2* 6th -0.18 0.31 -0.8 – 0.4 -0.6 0.37 -1.3 – 0.1 dental intern ref ref ref ref ref ref cumulative gpa 4.5-5 1.18 1.16 -1.1– 3.5 3.2 1.38 0.5 – 5.9* 4-4.49 0.97 1.15 -1.3 – 3.2 2.9 1.38 0.2 – 5.6* 3.5-3.99 0.66 1.17 1.6 – 3.0 2.2 1.40 -0.5 – 5.0 3-3.49 1.19 1.28 -1.3 – 3.7 2.7 1.50 -0.3 – 5.7 2.5-2.99 ref ref ref ref ref ref marital status single -2.4 0.89 -1.1 – 1.5 0.4 1.06 -1.7 – 2.5 married ref ref ref ref ref ref * statistically significant; p <0.05. er: standard error; ci: confidence interval; gpa: grade point average; ref: reference. ian dentists were willing to assist during a bioterrorism event (10). our findings were also consistent with a cross-sectional study conducted among healthcare professionals in three emergency departments and poison control centres/clinical laboratories in riyadh, saudi arabia, which found that 68.7% of respondents were willing to provide care during an attack (15). among the respondents, only 23.1% had received bioterrorism training. similarly, a study of physicians and nurses in riyadh found that 20.6% were trained in bioterrorism (15). in comparison, two previous studies showed that only 4.5% of dental students in india and 5.5% of dental professionals in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index l. bahanan et al. 6 figure 1: dental students’ perceived need for education and willingness to provide care during bioterrorism attacks. new england had attended a course on bioterrorism (13,14). in light of the increase in bioterrorism incidents worldwide, these percentages are considered low, especially because the literature has demonstrated that dentists have been effective in handling catastrophic events (7). in a study by nofal et al., the percentage of respondents who reported knowing where to take a bioterrorism course was higher than in our study (55.5% vs. 37.0%, respectively) (15). another study of a sample of family physicians with an active membership in the american academy of family physicians revealed that 56% of the respondents knew where to obtain bioterrorism training (16). this may be due to the fact that the study included physicians, nurses and other members of the emergency department team, whereas our study included undergraduate dental students and interns. our study showed that the mean total number of roles that students perceived that a dentist should play during a bioterrorism event was 8.3 ± 2.4 out of 10. this was consistent with a study of indian undergraduate dental students, which reported the mean number of roles as 8.73 ± 2.1 (13). however, a study conducted on new england dental professionals showed a slightly lower mean total number of roles at 5.9 ± 2.7 (14). the higher mean total number of roles among the indian undergraduate students and in our findings might be attributed to the fact that these studies were conducted after the covid-19 pandemic, when students had become more aware of the importance of dental professionals’ involvement and assistance during a catastrophic disaster. in agreement with previous studies, we found that more education about bioterrorism is needed (7,11,13–15,17). dental interns had significantly higher scores on selfperceived knowledge of bioterrorism than undergraduate students. dental interns also reported a higher number of roles for dentists in a bioterrorist attack than undergraduates, which is consistent with a previous study, which found that postgraduate dental students scored higher than undergraduate dental students on this topic (13). this may be due to the postgraduate students’ and interns’ clinical experience and greater community awareness than the undergraduates. however, we could not compare the overall score in our study with those of previous studies because the method of calculation was different. our sample of dental students indicated that cpr, vaccinations, and record-keeping were some of the most commonly mentioned roles they could perform during a bioterrorism event. the survey sample of new england dental professionals showed that 46.3% believed that dentists could help administer vaccines (14), compared to 87.7% of our respondents. the difference may be explained by our study being conducted after the covid-19 pandemic, during which some dental professionals were involved in administering vaccines through the ministry of health (18). in 2003, at a workshop on bioterrorism preparedness, the ada and the american dental education association conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e40 cluded that dental professionals should be knowledgeable about bioterrorism agents, trained to respond appropriately during an attack and capable of communicating surveillance data effectively (7,11). the role of dental schools in this process is crucial. however, adding bioterrorism training to the dental school curriculum can be challenging due to regional differences, core curriculum management, and financial restrictions (11). chmar et al. proposed three scenarios to improve students’ knowledge of bioterrorism: first, to create a new course that would provide bioterrorism training to students; second, to seamlessly integrate terrorism education into existing courses; and third, to combine the two previous scenarios by incorporating training into the existing curriculum as well as a culminating course (11). 5. limitations to our knowledge, this is the first study to assess dental students’ preparedness to deal with a bioterrorism event in saudi arabia. this study has several limitations. first, the study design is cross-sectional, which precludes making causal inferences. second, the sample consisted of students from one university, limiting the generalisability of the results. third, the study is limited to undergraduate dental students and does not include postgraduate dental students, hygienists, or dental assistants. since cross-sectional studies are subject to selection bias, we attempted to minimize non-response bias by following up with non-responders. although this study has limitations, its significance lies in identifying the need for dental students to receive additional training and education in bioterrorism. there are many ways in which dental professionals can receive bioterrorism training, including undergraduate courses, continuing education programmes, and online courses (15). hence, future research should focus on training programmes aimed at improving dental professionals’ readiness for bioterrorism events. 6. conclusion the increasing threat of bioterrorism worldwide necessitates the education and training of all healthcare professionals in bioterrorism. regardless of whether dental students intend to participate in addressing bioterrorism attacks, they should be familiar with the necessary knowledge and control measures to counter such attacks. this preparation could be achieved by incorporating bioterrorism education into dental curricula. 7. declarations 7.1. acknowledgments we acknowledge dental students and interns at king abdulaziz university who participated in this study. 7.2. conflict of interest the authors declare that they have no competing interests. 7.3. fundings and supports this study did not receive any funding. 7.4. authors’ contribution lb conceived the project idea with ms. oa and aa collected the data and drafted the manuscript. lb analysed the data. lb, ms, and ma critically reviewed the manuscript. all authors read and approved the final manuscript. 7.5. ethics approval this study was reviewed and approved by the institutional review board at king abdulaziz university faculty of dentistry, jeddah, saudi arabia (#364-12-21). all methods were performed in accordance with the principles of the declaration of helsinki. 7.6. consent for publication all participants provided written informed consent. 7.7. availability of data and materials the datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request. references 1. gupta v, bankar n, chandankhede m. the covid-19 an agent for bioterrorism?. j pharm res int. 2021; 33(40b):279-284. 2. prakash n, sharada p, pradeep g. bioterrorism: challenges and considerations. j forensic dent sci. 2010;2(2):59. 3. rathish b, pillay r, wilson a pv. comprehensive review of bioterrorism. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022. available from: http://www.ncbi.nlm.nih.gov/pubmed/29630269. 4. nathan mde, sri sakthi d. dentistry and mass disaster – a review. j clin diagn res. 2014;8(7):ze01-3. 5. flores s, mills se, shackelford l. dentistry and bioterrorism. dent clin north am. 2003;47(4):733-744. 6. han sz, alfano mc, psoter wj, rekow ed. bioterrorism and catastrophe response: a quick-reference guide to resources. j am dent assoc. 2003;134(6):745. 7. guay ah. dentistry’s response to bioterrorism: a report of a consensus workshop. j am dent assoc. 2002;133(9):1181-1187. 8. seneviratne cj, lau mwj, goh bt. the role of dentists in covid-19 is beyond dentistry: voluntary medthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index l. bahanan et al. 8 ical engagements and future preparedness. front med. 2020;7:566. 9. bhoopathi v, mashabi so, scott te, mascarenhas ak. dental professionals’ knowledge and perceived need for education in bioterrorism preparedness. j dent educ. 2010;74(12):1319-1326. 10. katz ar, nekorchuk dm, holck ps, hendrickson la, imrie aa, effler p v. dentists’ preparedness for responding to bioterrorism: a survey of hawaii dentists. j am dent assoc. 2006;137(4):461-467. 11. chmar je, ranney rr, guay ah, haden nk, valachovic rw. incorporating bioterrorism training into dental education: report of ada-adea terrorism and mass casualty curriculum development workshop. j dent educ. 2004;68(11):1196-1199. 12. sample size calculator by raosoft, inc. 2022. available from: http://www.raosoft.com/samplesize.html. 13. bhatt s, rajesh g, thakur d. knowledge, perceived need for education, and willingness to participate in bioterrorism preparedness among students in an indian dental institute: a questionnaire study. med j dr dy patil univ. 2017;10(6):526-531. 14. scott te, bansal s, mascarenhas ak. willingness of new england dental professionals to provide assistance during a bioterrorism event. biosecur bioterror. 2008;6(3):253-260. 15. nofal a, alfayyad i, aljerian n, et al. knowledge and preparedness of healthcare providers towards bioterrorism. bmc health serv res. 2021;21(1):426. 16. chen fm, hickner j, fink ks, galliher jm, burstin h. on the front lines: family physicians’ preparedness for bioterrorism. j fam pract. 2002;51(9):745-750. 17. sharma d, mishra a, newaskar v, khasgiwala a. bioterrorism: law enforcement, public health & role of oral and maxillofacial surgeon in emergency preparedness. j maxillofac oral surg. 2016;15(2):137. 18. ministry of health. covid-19 vaccination training platform. 2020. available from: https://moh.cvdvaccinetraining.com/. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e11 or i g i n a l re s e a rc h the effect of l-citrulline supplementation on outcomes of critically ill patients under mechanical ventilation; a double-blind randomized controlled trial mohammad reza asgary1, sayid mahdi mirghazanfari2, ebrahim hazrati3, vahid hadi1, mojgan mehri ardestani4, faeze bani yaghoobi5, saeid hadi1∗ 1. department of health, school of medicine, aja university of medical sciences, tehran, iran. 2. department of physiology and iranian medicine, school of medicine, aja university of medical sciences, tehran, iran. 3. trauma research center, aja university of medical sciences, tehran, iran. 4. department of persian medicine, faculty of medicine, aja university of medical sciences, tehran, iran. 5. instructor, department of military nursing, faculty of nursing, aja university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: effective parenteral and enteral amino acid replacement is crucial for critically ill patients with altered amino acid metabolism. this study aimed to assess the effects of l-citrulline supplementation on the clinical and laboratory outcomes in critically patients. methods: this was a double-blind placebo-controlled randomized clinical trial. 82 critically ill patients who were expected to receive mechanical ventilation for more than 72 hours were selected. the patients were assigned to either a placebo or an intervention group. the patients in the placebo group received 10 gr of microcrystalline cellulose and the ones in the intervention group were given l-citrulline daily for 7 days. serum levels of fasting blood sugar (fbs), lipid profile, hepatic enzymes, serum electrolytes, urea nitrogen, creatinine, and c-reactive protein (crp) were evaluated before and after the intervention. duration of invasive ventilation, intensive care unit (icu) length of stay, ventilator-free days, and 28-day mortality rate were recorded and compared between groups. results: eighty-two patients completed the trial. no statistically significant differences were observed between the two groups in terms of age (p = 0.46), sex (p = 0.49), body mass index (bmi) (p = 0.41), sequential organ failure assessment (sofa) score (p = 0.08), clinical pulmonary infection score (cpis) score (p = 0.76), acute physiology and chronic health evaluation (apache ii) score (p = 0.58), risk factors (p = 0.13), icu stay before randomization (p = 0.32), and reason of admission (p = 0.50) before the intervention. citrulline group had a notable reduction in fbs (p = 0.04), total cholesterol (tc) (p = 0.02), low density lipoprotein (ldl-c) (p <0.001) and high-sensitivity crp (hs-crp) (p <0.001). also, a significant increase in lactate dehydrogenase (ldh) concentration (p <0.001) was observed in the intervention group at the end of the trial. total duration of invasive ventilation and the mean sofa score on 7th day were significantly lower in the citrulline group compared to the control group. moreover, a significant increase in days alive and ventilator-free days within 28 days after admission was found in the citrulline group at the end of the trial. also, there were no significant differences between the groups in terms of mortality rate during intervention, serious adverse events, endotracheal intubation, the use of tracheotomy or non-invasive ventilation after extubation, length of icu stay, icu-free days at 28 days, and cpis and apache ii scores. for mortality, in the citrulline group, there was two deaths compared to eight deaths in the control group. this resulted in an absolute risk reduction (arr) of 14.05% (95% ci: 0.39–27.71%) and a number needed to treat (nnt) of 7.1 (95% ci: 3.6–29.5), regarding mortality. conclusion: the results of the present study demonstrated the probable positive effects of citrulline supplementation on lipid profile, hs-crp levels, duration of invasive ventilation, and sofa score. also, l-citrulline consumption may increase the probability of survival without mechanical ventilation. keywords:l-citrulline; critical illness; ventilation; intensive care units; treatment outcome; clinical trial cite this article as: asgary mr, mirghazanfari sm, hazrati e, hadi v, et al. the effect of l-citrulline supplementation on outcomes of critically ill patients under mechanical ventilation; a double-blind randomized controlled trial. arch acad emerg med. 2023; 11(1): e11. https://doi.org/10.22037/aaem.v11i1.1774. ∗corresponding author: saeid hadi; department of health, aja university of medical sciences, fatemi street, tehran, iran. p. o. box: 1416643931, tel: + this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mr. asgary et al. 2 1. introduction providing the appropriate nutrition therapy in an intensive care unit (icu), especially for critically ill patients, is essential to improve the metabolic and clinical outcomes (1). critical illnesses, such as major trauma and sepsis are characterized by a high level of stress/inflammation. regulation of amino acid metabolism is altered by neuroendocrine changes and cytokine effects due to stress and inflammation, respectively (2). the 2019 european society for clinical nutrition and metabolism (espen) guidelines recommend nutrition therapy to all critically ill patients staying in the icu for more than 48 hours (1). catabolic conditions in critically ill and injured patients cause an increase in energy expenditure and muscle wasting (3, 4). muscle protein degradation and loss of contractile protein can affect the diaphragm, which is the main inspiratory muscle. people with respiratory problems stay on ventilators for prolonged periods (5). for critically ill and injured patients, amino acids are crucial for nutritional and metabolic support (6). citrulline, which has gained attention recently, is included in these immune-nutrition (imn) formulas, along with arginine, n3 fatty acids, glutamine, antioxidants, and nucleic acids (7). as our knowledge of altered amino acid metabolism in such patients increases, it is crucial to develop more effective parenteral and enteral amino acid replacement products. following trauma and surgery, arginine and citrulline levels appear to decrease in critically ill patients (7-10). moreover, these amino acids are reversely correlated with levels of cytokines and inflammatory markers (11). a growing body of evidence shows that cytokines can contribute to the emergence of critical illness (12). cytokines are strongly related to higher disease severity in these states, while the persistence in the spread of the cytokinesis is associated with improvement in multiple organ failure (mof) (13). orally ingested l-citrulline can result in the biosynthesis of l-arginine and, l-citrulline (14) ,and also enhance arginine bioavailability in the circulation, which acts as a precursor for nitric oxide (no) formation (15). no level could regulate vasodilation, blood flow, and muscle oxygenation (16, 17). l-citrulline has been found to be more effective than larginine supplementation for formation of no, which can be due to the fact that arginine might be metabolized by arginase and transformed to urea and ornithine, making it less available to nitric oxide synthase for producing no and citrulline(18)(19). 98/218/895 556, fax: + 98/218/8984 861, email: s.hadinu@yahoo.com, orcid: https://orcid.org/0000-0003-2770-7084. several studies have examined the effects of l-arginine supplementation on icu patients using arginine-rich imn formulas, including other compounds (20-22). based on a recent study on critical care, citrulline plasma levels are extremely low in patients with sepsis and even lower in those with acute respiratory distress syndrome (ards) (12). according to one viewpoint, plasma citrulline levels could be linked with better vision in critically ill patients. most importantly, plasma citrulline levels are low in the majority of these patients (23-25). low plasma citrulline levels are related to poor prognosis (24, 25). plasma citrulline and cresponsive protein (crp) fixations are conversely connected (24-26). although several clinical studies have demonstrated the favourable effects of citrulline on critically ill patients (27, 28), it is yet not confirmed to be effective as a solitary treatment and further controlled clinical trials are needed to examine the effects of citrulline on clinical outcomes, such as the respiratory capacity and the duration of ventilation in these patients. therefore, the aim of the current study was to evaluate the effect of oral l-citrulline supplementation on fbs, lipid profile, hepatic enzymes, serum electrolytes, urea nitrogen, creatinine, crp, duration of invasive ventilation, icu length of stay, ventilator-free days, and 28-day mortality rate in ventilated intensive care unit patients. 2. methods this was a randomized clinical trial performed on intensive care unit (icu) patients admitted to imam reza hospital affiliated with the aja university of medical sciences, tehran, iran, from december 21, 2021 to may 27, 2022. the research ethics committee of aja university of medical sciences approved the study protocol (ir.ajaums.rec.1400.269). we registered the present trial on the iranian registry of clinical trials website (http://www.irct.ir, identifier: irct20210920052530n1). all patients’ families provided written informed consent after a full explanation of the study. 2.1. participants this study was performed on adult critically ill patients. only subjects that were under invasive ventilation either through intubation or tracheotomy tube and required ventilation for at least 72 hours after study entry and expected to survive and remain in the icu for at least 96 hours after were included. the study exclusion criteria were as follows: less than 18 years old, pregnancy, previous allergy to citrulline or arginine, a history of gastrointestinal disease, digestive tract surgery, intestinal obstruction, paralytic ileus, intestinal ischemia, septic patients, and hyperthyroidism. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e11 2.2. randomization and allocation random allocation software (ras) was used for randomization. during the first 24 hours of invasive ventilation, the subjects were randomly assigned to each group in a centralized, blinded manner by means of an assignment sequence that was generated by computer. in addition, the acute physiology, and chronic health evaluation (apache) ii (score dichotomized as ≤ 15 or > 15) was used to assess severity of disease at the time of inclusion. random block sizes were utilized to balance the list. furthermore, investigators, patients, and research staff did not know the group of the participants. 2.3. study protocol participants in placebo (n=42) and citrulline (n=40) groups received 10 gram/day microcrystalline cellulose and lcitrulline powder (karen pharma & food supplement co., iran) for 7 days, respectively. blood samples were drawn before and after the 7-day intervention. acute-phase proteins (apps) as immunology factors, complete blood count (cbc), blood urea nitrogen (bun), creatine, albumin, glycemic status, lipid profile, and liver function were determined before and after the intervention. demographic characteristics, physiological variables, and other clinical and laboratory data were collected. data on the days with mechanical ventilation were collected within 28 days. enteral feeding started for all patients within 24-48 hours of admission in hospital. all subjects received the same hospital prepared enteral formulation (hpf), which contained 42.8% carbohydrates, 16.6% protein, and 34.2% fat. 2.4. measurements clinical outcomes the number of days free from mechanical ventilation for at least 48 consecutive hours and alive is defined as ventilatorfree days within the first 28 days. if patients were discharged prior to the end of study period, they are considered as alive without mechanical ventilation. also, for subjects who died, the ventilator-free days are omitted. data on all-cause mortality, icu-free days, and mechanical ventilation duration at 28 days plus both sequential organ failure assessment (sofa) score and clinical pulmonary infection score (cpis) on the first and seventh days were measured in addition to other outcomes. the severity of illness was evaluated using apache ii on the day of admission blood sample collection fasting blood samples (10 ml) were taken at baseline (day 0) and at the end of the trial (day 7) early in the morning and after an overnight fast. serum was immediately separated by centrifugation at 3400 rpm for 3 minutes. serum samples were stored at -80°c until assayed. laboratory investigation crp was measured via the method of agglutination of latex particles on the slide (enison co kits). albumin was assessed using a commercially available enzyme-linked immunosorbent assay (elisa) kit (abcam). bun was determined using enzymatic methods. alanine transaminase (alt), aspartate transaminase (ast), and lactate dehydrogenase (ldh) were measured based on the method recommended by the ifcc (international federation of clinical chemistry). sample size and statistical methods the minimum sample size was determined as 30 subjects in each group. the calculation is based on the mean ±sd of hscrp determined by barkhidarian et al. (19) considering α = 0.05 and power of 80%. considering a possible dropout of 35%, 40 subjects were included in each group. data were presented as mean ± sd. we used the kolmogrovsmirnov test to examine the normal distribution of variables. log transformation was conducted for nonnormally distributed variables. independent sample t-test and paired student’s t-test were employed to identify the effect of the intervention on outcome variables. the chi-square test was applied to compare the relative or absolute frequency. analysis of covariance (ancova) was used for comparisons between the two groups post-intervention after adjusting for baseline values. paired t-test was used to compare differences from baseline to post-intervention period within groups. absolute risk reduction (arr) and the number needed to treat (nnt) were also calculated (29). the statistical package for the social sciences (spss, version 19; chicago, il) was utilized to carry out the statistical analysis, and a p-value of < 0.05 was regarded statistically significant. 3. results 3.1. baseline characteristics of studies cases from december 21, 2021 to may 27, 2022, a total of 90 patients were randomly assigned to the intervention (n=45) and placebo (n=45) groups. after randomization, there was drop out throughout the investigation and finally 40 subjects in the citrulline group and 42 subjects in the placebo group completed the trial. 5 and 3 participants in the citrulline and placebo groups, respectively, were excluded after randomization due to the poor adherence to the intervention (figure 1). table 1 shows the baseline characteristics of the patients in the l-citrulline group and the placebo group. the mean age of the participants in the l-citrulline and the placebo groups were 52.2 ± 18.4 and 49.9 ± 19.0 years, respectively. all baseline characteristics of study participants were well balanced between groups and no statistically significant differences were observed between the two groups in terms of age (p = 0.46), sex (p = 0.49), bmi (p = 0.41), sofa score (p = 0.08), this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mr. asgary et al. 4 cpis score (p = 0.76), apach ii score (p = 0.58), risk factors (p = 0.13), icu stay before randomization (p = 0.32), and reason of admission (p = 0.50) before the intervention. 3.2. comparing the outcomes of intervention laboratory parameters among the laboratory variables, as presented in table 2, citrulline group had a notable reduction in fbs (p = 0.04), total cholesterol (tc) (p = 0.02), low density lipoprotein (ldlc) (p <0.001) and high-sensitivity crp (hs-crp) (p <0.001). also, a significant increase in ldh concentration (p <0.001) was observed in the intervention group compared to the control group after adjusting for baseline values at the end of the trial. non-significant differences were found between groups in term of albumin (p = 0.58), triglyceride (tg) (p = 0.68), high density lipoprotein (hdl-c) (p = 0.59), ast (p = 0.22), alt (p = 0.75), and bun (p = 0.40). serum concentrations of creatine (p = 0.01) significantly decreased during 7 days in patients receiving citrulline, while such effect was not observed in the placebo group. considering that no adverse side effects were reported, citrulline was well tolerated. disease severity and disposition as demonstrated in table 3, the total duration of invasive ventilation and the mean sofa score on the 7th day were significantly lower in the citrulline group compared to the control group. moreover, a significant increase in days alive and ventilator-free days within 28 days after admission was found after citrulline supplementation. also, there were no significant differences between the groups in terms of mortality rate during intervention, serious adverse events, endotracheal intubation, the use of tracheotomy or non-invasive ventilation after extubation, length of icu stay, icu-free days at 28 days, and cpis and apache ii scores. regarding mortality, in the citrulline group, there was two deaths compared to eight deaths in the control group. this resulted in an absolute risk reduction (arr) of 14.05% (95% ci: 0.39–27.71%) and a number needed to treat (nnt) of 7.1 (95% ci: 3.6–29.5), regarding mortality. 4. discussion based on the obtained findings, l-citrulline supplementation significantly decreased the serum levels of fbs, ldl-c, tc, and hs-crp, duration of invasive ventilation, and sofa score. also, serum ldh levels and days alive and ventilatorfree days within 28 days after admission were significantly increased by l citrulline supplementation. however, there was no difference in terms of other assessed variables after l citrulline supplementation. as mentioned above, serum levels of ldl-c and tc in the intervention group were lower than the placebo group. based on a prior study that was conducted on type 2 diabetes mellitus patients, an eight-week supplementation with lcitrulline powder showed a remarkable improvement on glucose homeostasis, some lipid profiles, and inflammatory biomarkers, which is consistent with our results (30). also, the efficacy of l-citrulline supplementation on lipid profile was assessed in numerous animal models. for example, kudo et al. investigated the effect of nine weeks of 1 gr/kg l-citrulline administration on the serum level of tg in rats. in this study, authors concluded that l-citrulline powder does not affect serum levels of tg (2). moreover, notable reduction in cholesterol levels without affecting tg concentration were detected as a result of l-citrulline (0.5 g/kg) supplementation for 11 weeks in rats with high-fat diet (31). the plausible hypolipidemic effects of l-citrulline may justify liver lipid metabolism improvement. l-citrulline can particularly suppress the expression of sterol regulatory element-binding protein 1 (srebp-1). srebp-1 expression is decreased with activation of adenosine monophosphate-activated protein kinase alpha (ampkalpha) (32). ampk is a cell strength sensor that merges different physiological indicators for power balance restoration. specifically, it induces silencing of srebp-1 cleavage, its target gene expression, and the nuclear translocation. this results in the reduction of lipid accumulation and synthesis of fatty acids in hepatocytes (33). furthermore, it has been demonstrated that intervention with citrulline stimulates visceral fat lipolysis. hormone-sensitive lipase phosphorylation and down-regulation of glyceroneogenesis might be induced by l-citrulline, which leads to accelerated fatty acid launch from the adipose tissue (34). moreover, it is known that the phosphorylation and activation of ampkα in various tissues are raised through no produced by l-citrulline (35, 36). not finding notable variation in other lipid profiles can be justified by various factors such as small sample size, insufficient dosage, and short intervention interval. in contrast with the study that found a significant increase in serum ldh levels, an animal study performed by villareal et al. demonstrated a decrease in the expression of ldh after lcitrulline supplementation (37). regarding hepatic enzymes including alt and ast, in opposition to our results that recommended no remarkable effect of l-citrulline, a clinical trial done by darabi et al. indicated a statistically significant decrease in alt levels following l-citrulline supplementation (38). also, regarding kidney function, contrary to our results that presented no favourable effect by l-citrulline, a recent animal study by hashemi et al. concluded that l-citrulline could significantly reduce the levels of bun and creatinine in rats (39). the discrepancies between aforementioned findings may result from the different nature of the studies and dissimilar dosage and duration of l-citrulline supplementation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e11 our study exhibited that l-citrulline powder notably decreased the duration of invasive ventilation. this finding is consistent with the results of a study conducted by lauterbach et al. in 2018, which measured the effectiveness of l-citrulline supplementation in treating pulmonary hypertension. this study finally proposed that treatment with lcitrulline may be an alternative and potentially useful treatment in the prevention or treatment of chronic pulmonary hypertension in infants (40). also, an animal study investigated the efficacy of l-citrulline on alveolar development and lung condition in newborn rats. the results of this research indicated that l-citrulline therapy prevents lung damage caused by hyperoxia and high blood pressure in newborn rats (41). furthermore, l-citrulline may be a new therapeutic alternative for inhaled no and, prevent bronchopulmonary dysplasia. in addition, oral l-citrulline, as a precursor of no, improved symptoms of sickle cell disease in children and reduced pulmonary blood pressure after surgery for congenital heart disease (42). orally ingested lcitrulline can also enhance arginine bioavailability in the circulation and act as a precursor for nitric oxide (no•) formation (15). no• levels could regulate vasodilation, blood flow, and muscle oxygenation (16, 17). although no side effects were previously reported for l-citrulline, oral administration of l-arginine in high doses could result in nausea, vomiting, diarrhea, headache, flushing, and numbness, owing to intestinal and hepatic conversion of l-arginine to ornithine and urea. orally ingested l-citrulline can mainly have a more beneficial effect compared to l-arginine (43). the sofa score evaluates blood pressure and the function of neurological system, blood, liver, and kidney. a higher sofa score indicates a higher chance of mortality (44). according to the findings of the present study, the sofa score in the group that received l-citrulline was notably lower in comparison to the control group. based on previous investigations, l-citrulline therapy induced an anti-inflammatory profile and obviously protected against kidney dysfunction through improving the function of glomerulus and its associated tubule (45). in addition, l-citrulline amino acid consumption exerts beneficial effects on cardiometabolic health, glucose homeostasis, and protein and lipid metabolism through direct and indirect pathways (46-48). moreover, l-citrulline intake may truncate the required time for complete myocardial depolarization and repolarization. thus, l-citrulline ingestion transiently modifies myocardial blood supply and improves the energy supply required for faster recovery in restoring atp-dependent ionic exchanges. taking this supplement can even control blood pressure in people with hypertension. the findings of a systematic review and metaanalysis showed that l-citrulline supplementation reduced the systolic blood pressure by 4 mmhg (49). hs-crp, a measurable protein in the blood, increases in the body during systematic inflammation. measurement of this index in the blood is used to determine the risk of cardiovascular diseases and other inflammatory-related complications. based on our results, l-citrulline supplementation significantly decreased hs-crp levels. in line with our findings, abbaszadeh et al. found a notable drop in hs-crp levels in patients who received 10 g l-citrulline daily for 10 days (50). also, another study demonstrated that an increase in lcitrulline concentrations caused a considerable reduction in hs-crp production in obese rats with diabetes (51). several in vitro and in vivo models proposed that l-citrulline supplementation caused a remarkable reduction in inflammation by inhibiting the expression of nf-kb as an important transcription factor involved in the inflammatory response (52). 5. limitations among the limitations of this study was the short duration of the follow-up period as well as the budget restrictions, which prevented us from examining the complete profile of inflammatory biomarkers. moreover, our participants were ill patients over 18 years old, and consequently, our findings may not apply to people of other ages and health conditions. finally, although several potential confounders were considered in the statistical analysis, some other unknown confounders could affect the obtained results and lead to bias. 6. conclusions in conclusion, our finding proposed that l-citrulline supplementation decreased the serum levels of fbs, ldl-c, tc, and hs-crp, duration of invasive ventilation, and sofa score. on the other hand, serum ldh levels and days alive and ventilator-free days within 28 days after admission significantly increased with l citrulline supplementation. although obtained findings suggested that l citrulline supplementation could improve some clinical outcomes in critically ill patients, further well-designed clinical trials with larger sample size and longer follow-up period are required to verify its favourable effects in ventilated intensive care unit patients. 7. declarations 7.1. acknowledgments we are sincerely grateful to the patients who participated in our research. 7.2. conflict of interest the authors declare that they have no conflicts of interest. 7.3. fundings and supports the research vice chancellor of aja university of medical sciences, tehran, iran, financially supported this research this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mr. asgary et al. 6 and provided the drugs (grant number 97001782). 7.4. authors’ contribution mra, sh, smm, eh and va studied concept and designed the study. mra, eh and fby collected data. mra, sh, smm, mma and vh analyzed and interpreted data. mra drafted whole of the manuscript. all authors read and approved the final version of manuscript. 7.5. ethics approval the protocol of the study was approved by the research ethics committees of aja university of medical sciences (ir.ajaums.rec.1400.269). 7.6. consent for publication all participants provided written informed consent. 7.7. availability of data and materials the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. references 1. ginguay a, de bandt jp, cynober l. indications and contraindications for infusing specific amino acids (leucine, glutamine, arginine, citrulline, and taurine) in critical illness. curr opin clin nutr metab care. 2016;19(2):161-9. 2. kany s, vollrath jt, relja b. cytokines in inflammatory 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comparing the baseline characteristics of studied groups characteristic l-citrulline placebo p value (n = 40) (n = 42) age (year) mean ± sd 52.5 ± 18.4 49.9 ± 19.0 0.46 gender male 21 (52.5) 26 (59.09) 0.49 female 19 (47.5) 16 (40.91) body mass index (kg/m2) mean ± sd 27.2 ± 8.0 26.7 ± 9.1 0.4 disease severity sequential organ failure assessment 8.2 ± 0.5 8.4 ± 0.55 0.08 clinical pulmonary infection score 3.4 ± 1.6 3.1 ± 1.0 0.76 apache ii score 16.77 ± 4.3 17.3 ± 4.6 0.58 icu stay before randomization (day) median (iqr) 1 (0-2) 1 (0-1) 0.32 comorbidities and risk factors cardiovascular disease 3 (7.5) 3 (7.1) 0.13 diabetes mellitus 15 (37.5) 20 (47.6) hypertension 24 (60.0) 31 (73.8) neurological diseases 1 (2.5) 1 (2.3) respiratory disease 13 (32.5) 10 (23.8) reason for admission pneumonia 14 (35.0) 15 (35.7) surgical 10 (25.0) 9 (21.4) chronic obstructive pulmonary disease 5 (12.5) 7 (16.6) 0.5 acute respiratory distress syndrome 5 (12.5) 6 (14.2) stroke 2 (5.0) 2 (4.7) trauma 4 (10.0) 5 (11.9) data are presented as mean ± standard deviation (sd), frequency (%), or median (interquartile range; iqr). apache ii score: acute physiology and chronic health evaluation. ii score; icu: intensive care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mr. asgary et al. 10 table 2: comparing the laboratory variables between the l-citrulline-treated (n=40) and placebo (n=42) groups before and one week after intervention factors baseline after intervention p value albumin l-citrulline 3.67 ± 0.51 3.31 ± 0.54 0.58 placebo 3.61 ± 0.44 3.38 ± 0.51 0.67 fbs (mg/dl) l-citrulline 106.93 ± 15.28 93.23 ± 9.79 0.04 placebo 106.96 ± 16.28 100.89 ± 13.94 0.57 tg (mg/dl) l-citrulline 185.50 ± 44.34 136.41 ± 32.86 0.68 placebo 164.44 ± 53.77 155.61 ± 44.12 0.52 tc (mg/dl) l-citrulline 181.23 ± 41.00 163.86 ± 40.21 0.02 placebo 200.00 ± 34.06 190.77 ± 31.84 0.01 ldl-c (mg/dl) l-citrulline 118.78 ± 34.78 105.97 ± 37.22 <0.001 placebo 128.73 ± 34.82 120.48 ± 35.65 0.01 hdl-c (mg/dl) l-citrulline 35.01 ± 11.68 37.28 ± 11.43 0.59 placebo 33.49 ± 7.70 34.78 ± 7.78 0.35 hs-crp (mg/l) l-citrulline 3691.50 ± 644.67 2026.62 ± 246.82 <0.001 placebo 3964.23 ± 241.09 3360.44 ± 486.36 0.01 ast (u/l) l-citrulline 88.43 ± 22.48 117.98 ± 34.07 0.22 placebo 63.23 ± 24.14 117.63 ± 47.97 0.97 alt (u/l) l-citrulline 66.54 ± 34.61 107.34 ± 29.21 0.75 placebo 46.41 ± 18.79 135.22 ± 38.41 0.84 ldh (u/l) l-citrulline 63.93 ± 24.51 99.66 ± 31.37 <0.001 placebo 79.04 ± 32.75 117.42 ± 33.23 0.01 bun (mg/dl) l-citrulline 50.63 ± 24.42 47.25 ± 13.08 0.40 placebo 42.07 ± 15.02 44.05 ± 13.69 0.99 creatinine (mg/dl) l-citrulline 1.19 ± 0.56 0.78 ± 0.31 0.01 placebo 1.12 ± 0.23 0.96 ± 0.52 0.13 data are presented as mean ± standard deviation (sd). fbs: fasting blood sugar; tg: triglyceride; tc: total cholesterol; ldl-c: low density lipoprotein; hdl-c: high density lipoprotein; hs-crp: high-sensitive c-reactive protein; ast: aspartate aminotransferase; alt: alanine aminotransferase; ldh: lactate dehydrogenase; bun: blood urea nitrogen. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e11 table 3: comparing the clinical outcomes (after 28 days) and disease severity between the l-citrulline-treated (n=40) and placebo (n=42) groups variables l-citrulline placebo p value mortality rate during intervention 2 (5.0) 8 (19.0) 0.61 serious adverse events 1 (2.5) 2 (4.5) 0.82 endotracheal intubation 40 (100.0) 41 (97.5) 0.99 niv after extubation 13 (32.5) 16 (38.0) 0.39 all-cause mortality 7 (17.5) 9 (21.5) 0.85 duration of invasive ventilation (hour) 112.5 ± 59 139 ± 61.35 0.04 days alive and ventilator-free 6.6 ± 1.6 4 ± 1.25 < 0.001 length of icu stay (days) 7 ± 5.5 8 ± 5.5 0.41 icu-free days 2.1 ± 1.75 2.0 ± 1.7 0.79 sofa score 1th day 8.2 ± 0.5 8.4 ± 0.55 0.08 7th day 6.1 ± 0.6 7.5 ± 1.2 < 0.001 p value 0.08 0.38 cpis score 1th day 3.4 ± 1.6 3.1 ± 1.0 0.31 7th day 2.9 ± 1.1 2.7 ± 0.9 0.37 p value 0.73 0.96 apache ii score 1th day 16.77 ± 4.3 17.3 ± 4.6 0.59 7th day 22.9 ± 7.6 22.0 ± 7.6 0.59 p value 0.82 0.96 data are presented as mean ± standard deviation (sd) or frequency (%). abbreviations: icu: intensive care unit; sofa: sequential organ failure assessment; cpis: clinical pulmonary infection score; apache ii score: acute physiology and chronic health evaluation ii score; niv: non-invasive ventilation. adverse events were considered serious when they required intensive care procedures (use of vasopressors, haemodialysis, central venous catheterization, cardiac pacing, or tube thoracostomy) or surgery, and events that prolonged hospitalization or resulted in persistent or major disability or incapacity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index mr. asgary et al. 12 figure 1: flowchart of patient enrollment. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references archives of academic emergency medicine. 2023; 11(1): e34 or i g i n a l re s e a rc h modified shock index as a predictor of admission and inhospital mortality in emergency departments; an analysis of a us national database bachar hamade1, jamil d. bayram2, yu-hsiang hsieh2, basem khishfe3, nour al jalbout4∗ 1. center for emergency medicine, main campus and department of intensive care and resuscitation, cleveland clinic foundation, cleveland, ohio. 2. department of emergency medicine, johns hopkins university school of medicine, baltimore, maryland. 3. department of emergency medicine, st. elizabeth’s hospital, o’fallon, illinois. 4. department of emergency medicine, massachusetts general hospital, boston, massachusetts. received: february 2023; accepted: march 2023; published online: 29 april 2023 abstract: introduction: the modified shock index (msi) is the ratio of heart rate to mean arterial pressure. it is used as a predictive and prognostic marker in a variety of disease states. this study aimed to derive the optimal msi cut-off that is associated with increased likelihood (likelihood ratio, lr) of admission and in-hospital mortality in patients presenting to emergency department (ed). methods: we retrospectively reviewed data from the national hospital ambulatory medical care survey between 2005 and 2010. adults>18 years of age were included regardless of chief complaint. basic patient demographics, initial vital signs, and outcomes were recorded for each patient. then the optimal msi cut-off for prediction of admission and in-hospital mortality in ed was calculated. lr ≥ 5 was considered clinically significant. results: 567,994,402 distinct weighted adult ed patient visits were included in the analysis. 15.7% and 2.4% resulted in admissions and in-hospital mortality, respectively. msi > 1.7 was associated with a moderate increase in the likelihood of both admission (positive lr (+lr) = 6.29) and in-hospital mortality (+lr = 5.12). +lr for hospital admission at msi >1.7 was higher for men (7.13; 95% ci 7.11-7.15) compared to women (5.49; 95% ci 5.47-5.50) and for non-white (7.92; 95% ci 7.88-7.95) compared to white patients (5.85; 95% ci 5.84-5.86). for msi <0.7, the +lrs were not clinically significant for admission (+lr = 1.07) or in-hospital mortality (lr = 0.75). conclusion: in this largest retrospective study, to date, on msi in the undifferentiated ed population, we demonstrated that an msi >1.7 on presentation is predictive of admission and in-hospital mortality. the use of msi could help guide accurate acuity designation, resource allocation, and disposition. keywords: modified shock index; hospitalization; inpatients; hospital mortality; emergency service, hospital; probability cite this article as: hamade b, bayram jd, hsieh y, khishfe b, al jalbout n. modified shock index as a predictor of admission and in-hospital mortality in emergency departments; an analysis of a us national database. arch acad emerg med. 2023; 11(1): e34. https://doi.org/10.22037/aaem.v11i1.1901. 1. introduction the shock index (si) is a clinical metric obtained by dividing the heart rate (hr) by the systolic blood pressure (sbp). it was first described by allgower and burri (1) in 1967 and has been proposed to serve as an early indicator of clinical deterioration (2, 3). originally investigated in shock states, the si has been studied as a prognostic metric in a variety of disease ∗corresponding author: nour al jalbout; department of emergency medicine, massachusetts general hospital, 55 fruit street, boston, ma 02114. email: naljalbout@mgh.harvard.edu, tel: 001 (617) 726-7622, orcid: https://orcid.org/0000-0002-9369-0260. states including trauma, pneumonia, sepsis, gastrointestinal bleeding, and st segment elevation myocardial infarction (4-11). in the undifferentiated emergency department (ed) population, one recent large retrospective multicenter study found that si>1.3 was associated with a higher likelihood of hospital admission and in-hospital mortality (12). currently, most eds measure blood pressure non-invasively via automated blood pressure machines that rely on oscillometry. these machines measure mean arterial pressure (map) and extrapolate sbp and diastolic blood pressure (dbp), overestimating sbp compared to invasive arterial monitoring (13), which can lead to false hemodynamic reassurance. map is an important clinical metric driven this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. hamade et al. 2 table 1: baseline characteristics of studied emergency department patient visits variable number (%) age (years) 18-44 279,660,193 (53.1) 45-64 144,066,977 (27.4) ≥65 102,054,146 (19.5) sex male 299,216,051 (56.9) female 226,565,265 (43.1) race non-white 137,426,759 (26.1) white 388,354,557 (73.9) disposition admission 82,501,250 (15.7) in-hospital mortality 1,917,737 (2.4) by early changes in dbp, which defines perfusion pressure, and guides therapy in septic patients and early hemorrhagic states (14-16). in 2012, liu et al. introduced the modified shock index (msi), which is the hr divided by the map. they demonstrated that msi <0.7 or >1.3 were significantly associated with higher in-hospital mortality in a single center ed population (17). in another large prospective study of 9860 trauma patients, the same msi cut-offs outperformed si and traditional vital signs as predictors of mortality (18). since then, the predictive and prognostic utilities of msi have been studied in a variety of disease states such as sepsis and myocardial infarction (19-25). however, literature regarding its optimal predictive cut-offs and utility in the general undifferentiated ed population is limited (26, 27). the main objective of this study is to derive an msi threshold that predicts both admission and in-hospital mortality in the undifferentiated ed population based on the initial presenting hr and map, irrespective of clinicians’ subjective clinical judgements. the secondary objective is to analyze the performance of different msi thresholds when performing subgroup analysis based on age, sex, and race. 2. methods 2.1. study design and setting we retrospectively analyzed ed visits from 2005 to 2010 from the national hospital ambulatory medical care survey (nhamcs), the largest nationally representative database of utilization and provision of ed services in the united states, using a weighted sample of all u.s. ed visits reported in the survey. the study was granted exempt status by our institution’s review board (irb00151493). the nhamcs is a nationally representative survey conducted by the centers for disease control and prevention (cdc) and the national center for health statistics (28). it includes an estimated 120 million encounters annually obtained from probability sampling of ed visits in the 50 states and the district of columbia, excluding visits to federal, military and veteran administration hospitals. 2.2. participants adult patient visits above 18 years of age were included. encounters with insufficient data to calculate the msi in addition to encounters resulting in ed deaths were excluded (since our main outcomes of interest were admissions and in-hospital mortality). 2.3. data gathering data is collected from ed visit medical records during a randomly assigned four-week period by nhamcs personnel under the supervision of field representatives. staff members independently checked 10% of the data for accuracy with an error rate ranging from 0.3% to 0.9% for various items on the survey (28). between 352 and 389 hospitals agreed to participate in the survey from the year 2005 to 2010, which constituted our study period. this data was publicly available with free access. the nhamcs does not include information on specific ed clinical management and condition fluctuation details. for each patient visit, basic patient demographics including age, sex and race, initial hr, sbp and dbp, and visit outcomes were recorded by trained coders following cdc’s national center for health statistics standardized nhamcs data collection protocol (28). from the initial sbp and dbp, map and subsequently the msi were calculated. the sbp and dbp were measured noninvasively at triage, as this is the standard across emergency rooms. for this exploratory study, effect modifiers were not considered in the data analysis plan. msi, the hr divided by the map, which was calculated as (2*dbp+sbp)/3, was the predictor of the primary outcomes. 2.4. outcome measures the primary outcome measures of our study were hospital admission and in-hospital mortality, which were based on the data coding on ed disposition and hospital discharge status, respectively. 2.5. data analysis descriptive data analysis was first performed to summarize key descriptive statistics of the study population. likelihood ratios (lrs) for a broad range of thresholds of msi for both outcomes were then calculated. positive lrs (+lrs) were used since they represent statistically robust measures of diagnostic accuracy independent of pretest probability, unlike positive and negative predictive values (29). since prior data suggests different likelihood of admission based on age, sex this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e34 and race, these variables were considered as potential confounders a priori. for this exploratory study, we performed sub-group analysis stratified by race (white vs. non-white), sex (women vs. men) and age group (18-44, 45-64 and ≥65 years) for the outcome of hospital admission to minimize the bias resulting from the potential confounding effect by age, sex, and race (30-32). with regards to in-hospital mortality, the original weighted sample size was less than 30 in each subgroup, and thus prevented stratifying the data by demographics due to the concern of generating invalid estimates. values of + lr are considered to be clinically significant when they are ≥ 5, with the range between 5 and 10 considered moderate increase in the likelihood of the outcome and ≥10 considered large and often conclusive for the likelihood of the outcome (29). 3. results 3.1. baseline characteristics of ed visits we identified 567,994,402 distinct weighted adult ed patient visits between the years 2005 and 2010. we excluded 660,207 (0.12%) visits of patients who died in the ed in addition to 42,213,086 (7.43%) visits due to incomplete records. 525,781,316 weighted patient visits were included in the final analysis, of which 299,216,051 (57%) were female, 388,354,557 (74%) were white and 279,660,193 (53%) were between the ages of 18 and 44 years. table1 summarizes the baseline characteristics of the studied ed visits. out of the 525,781,316 weighted patient visits included in this study, 82,501,250 (15.7%) unique ed visits resulted in in-hospital admissions, and 1,917,737 (2.4%) resulted in in-hospital mortality. 3.2. predictive value of msi for admission and in-hospital mortality an initial msi value of >1.7 was associated with a moderate increase in the likelihood of both admission and in-hospital mortality with a +lr of 6.29 (95% ci: 6.28-6.31) and 5.12 (95% ci: 5.10-5.14), respectively. for patients with an initial msi value of <0.7, the +lrs for admission and in-hospital mortality were not clinically significant with values of 1.07 (95% ci: 1.07-1.07) and 0.75 (95% ci: 0.75-0.75), respectively. likewise, for patients with msi value of >1.3, the +lrs for admission and in-hospital mortality were 2.55 (95% ci: 2.55-2.55) and 2.69 (95% ci: 2.68-2.70), respectively (tables 2 and 3). out of the 82,501,250 admitted patients, 2,011,388 (2.4%) had an initial msi value >1.7, and out of 1,917,737 patients who died, 215,337 (11.2%) had an msi>1.7 (tables 2 and 3). a total of 23,713,531 (4.51%) admitted patient encounters had msi <0.7 or msi >1.3 (table 2). among them, 800,831 (0.15%) patients died during hospitalization (table 3). the frequency of both outcomes at every msi cut-off is presented in tables 2 and 3. the areas under the receiver operating characteristic (roc) curve of msi in predicting the admission and in-hospital mortality were 0.454 (95%ci: 0.450-0.459) and 0.366 (95%ci: 0.339-0.393), respectively (figure 1). 3.3. +lr of msi stratified by age, sex, and race when stratified by age, sex, and race, +lr for hospital admission at msi >1.7 was higher for men (7.13; 95% ci: 7.11-7.15) compared to women (5.49; 95% ci: 5.47-5.50) and for nonwhite (7.92; 95% ci: 7.88-7.95) compared to white patients (5.85; 95% ci: 5.84-5.86) (table 4). admission +lrs for all age groups increased with increasing msi values, with the highest +lr being for patients aged 45-64 years (7.48; 95% ci 7.457.51) (table 4). sub-group analysis for in-hospital mortality outcome was not performed due to the small sample size, rendering +lr estimates unreliable. 4. discussion in the undifferentiated ed population, our study shows an association between an initial msi value >1.7 and a clinically significant increase in the likelihood of both outcomes, admission and in-hospital mortality, with +lrs of 6.29 and 5.12, respectively. to the best of our knowledge, this is the largest multicenter retrospective study of the general ed population, with 525,781,316 weighted ed patient encounters. these results are in line with a recent study describing an msi of >1.7 as a strong predictor of mortality. in this study, smischney et al. showed that within the first 24 hours of icu admission, patients with an elevated msi have a significant mortality risk (23). our study results indicate that the msi cut-off values of <0.7 and >1.3 introduced by liu et al. are not reliable predictors of mortality in the general ed population, with +lrs being significantly less than 5. it is important to note that there are important differences in the methodology between our study and that of liu et al. that may explain the differences in msi values. while both studies are similar in calculating the msi from the triage vital signs and defining one of the primary outcomes as in-hospital mortality, our study was a large multicenter study encompassing a more diverse patient population with a variety of disease states and complaints. liu et al. included only those patients that received intravenous (iv ) fluids because they were considered “real emergency” patients. the study of liu et al. analyzed a smaller total number of patients (22,161) in a different setting (china), with a wider age range, including those aged 10 years up to 100 years. our study analyzed more than 525 million ed visits, and was limited to those 18 years old and above. in our study, only 4.51% of the admitted patients and 0.15% of those who died as inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. hamade et al. 4 table 2: screening performance characteristics of modified shock index (msi) in different cut-offs for predicting the need for hospital admission msi number* admitted plr sensitivity specificity <0.3 781,336 126,089 1.03 (1.03-1.04) 0.15 (0.15-0.15) 99.85 (99.85-99.85) <0.4 1,462,308 374,241 1.85 (1.84-1.85) 0.45 (0.45-0.46) 99.75 (99.75-99.76) <0.5 6,658,809 1,623,417 1.73 (1.73-1.73) 1.97 (1.96-1.97) 98.86 (98.86-98.87) <0.6 30,810,315 6,097,638 1.33 (1.32-1.33) 7.39 (7.39-7.40) 94.43 (94.42-94.43) <0.7 89,440,729 14,817,168 1.07 (1.07-1.07) 17.96 (17.95-17.97) 83.17 (83.16-83.17) 0.5≤ & ≤0.7 83,149,111 69,917,576 0.98 (0.98-0.98) 15.77 (15.77-15.78) 83.96 (83.16-83.17) >0.7 435,973,396 67,646,298 0.99 (0.99-0.99) 81.99 (81.99 – 82.0) 16.91 (16.91-16.91) >0.8 344,098,058 55,261,912 1.03 (1.03-1.03) 66.98 (66.97-66.99) 34.84 (34.84-34.85) >0.9 239,969,027 41,744,323 1.13 (1.13-1.13) 50.60 (50.59-50.61) 55.28 (55.28-55.29) >1.0 148,962,698 29,618,270 1.33 (1.33-1.33) 35.90 (35.89-35.91) 73.08 (73.07-73.08) >1.1 87,173,982 20,246,957 1.63 (1.62-1.63) 24.54 (24.53-24.55) 84.90 (84.90-84.91) >1.2 49,130,138 13,537,356 2.04 (2.04-2.05) 16.41 (16.40-16.42) 91.97 (91.97-91.97) >1.3 27,631,575 8,896,363 2.55 (2.55-2.55) 10.78 (10.77-10.79) 95.77 (95.77-95.78) >1.4 15,649,057 6,045,761 3.38 (3.38-3.39) 7.33 (7.32-7.33) 97.83 (97.83-97.83) >1.5 9,131,844 3,972,421 4.14 (4.13-4.14) 4.81 (4.81-4.82) 98.84 (98.84-98.84) >1.6 5,678,149 2,779,613 5.15 (5.14-5.16) 3.37 (3.37-3.37) 99.35 (99.35-99.35) >1.7 3,728,673 2,011,388 6.29 (6.28-6.31) 2.44 (2.43 -2.44) 99.61 (99.61-99.61) >1.8 2,530,265 1,375,089 6.40 (6.38-6.41) 1.66 (1.66-1.67) 99.74 (99.74-99.74) data are presented with 95% confidence interval. *denotes the number of patient encounters included in the study in each specific msi category. plr: positive likelihood ratio. figure 1: area under the receiver operating characteristic (roc) curve of modified shock index in predicting the need for admission (left) and in-hospital mortality (right). patients had an msi<0.7 or >1.3. finally, our study showed that msi <0.7 was not a strong predictor of admission and inpatient mortality, which could mean that in the general ed population, a hypodynamic circulatory state is much more indicative of serious underlying pathology than a hyperdynamic state as liu et al. concluded. when stratified by groups, +lr for hospital admission stratified by race and sex were highest for non-white (7.92; 95% ci 7.88-7.95) and male patients (7.13; 95% ci 7.11-7.15). we could not identify specific causes for these differences without substratifying for confounders like age and comorbidities; however prior data demonstrates higher admission rates for non-white patients and males in certain disease states (30-32). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e34 table 3: screening performance characteristics of modified shock index (msi) in different cut-offs for predicting the in-hospital mortality msi number* admitted plr sensitivity specificity <0.3 113,160 1,737 0.58 (0.55-0.61) 0.09 (0.09-0.10) 99.84 (99.84-99.84) <0.4 319,606 9,786 1.17 (1.15-1.20) 0.51(0.50-0.52) 99.56 (99.56-99.57) <0.5 1,437,215 42,745 1.14 (1.13-1.15) 2.22 (2.21-2.25) 98.04 (98.04-98.04) <0.6 5,464,331 110,687 0.77 (0.76-0.77) 5.77 (5.74-5.80) 92.47 (92.47-92.49) <0.7 13,181,503 260,138 0.75 (0.74-0.75) 13.56 (13.52-13.61) 81.84 (81.84-81.86) 0.5≤ & ≤0.7 11,782,072 11,564,679 1.43 (1.43-1.44) 16.24 (16.24-16.25) 88.66 (88.62-88.71) >0.7 59,889,401 1,657,599 1.06 (1.06-1.06) 86.43 (86.39-86.48) 18.20 (18.19-18.21) >0.8 48,768,358 1,466,088 1.15 (1.15-1.15) 76.44 (76.39-76.51) 33.55 (33.54-33.57) >0.9 36,826,926 1,299,048 1.36 (1.36-1.36) 67.73 (67.67-67.80) 50.09 (50.08-50.11) >1.0 26,225,851 1,106,980 1.64 (1.63-1.63) 57.72 (57.65-57.79) 64.71 (64.71-64.73) >1.1 17,910,296 894,677 1.95 (1.95-1.96) 46.65 (46.58-46.72) 76.09 (76.09-76.11) >1.2 12,014,175 717,380 2.36 (2.36-2.36) 37.40 (37.34-37.48) 84.13 (84.12-84.14) >1.3 8,004,628 540,693 2.69 (2.68-2.70) 28.19 (28.13-28.26) 89.51 (89.51-89.52) >1.4 5,458,320 453,297 3.36 (3.35-3.37) 23.63 (23.58-23.70) 92.96 (92.96-92.98) >1.5 3,596,224 319,161 3.62 (3.60-3.62) 16.64 (16.59-16.70) 95.39 (95.39-95.40) >1.6 2,519,176 274,000 4.53 (4.51-4.54) 14.28 (14.24-14.34) 96.84 (96.84-96.85) >1.7 1,777,416 215,337 5.12 (5.10-5.14) 11.22 (11.18-11.27) 97.80 (97.80-97.81) >1.8 1,223,325 156,472 5.44 (5.42-5.47) 8.15 (8.12-8.20) 98.50 (98.50-98.50) data are presented with 95% confidence interval. *denotes the number of patient encounters included in the study in each specific msi category. plr: positive likelihood ratio. table 4: positive likelihood of modified shock index (msi) in different cut-offs for predicting the need for admission stratified by sex, race, and age category msi sex race age (year) female male non-white white 18-44 45-64 ≥65 <0.3 0.74 (0.73-0.75) 1.45 (1.44-1.46) 0.45 (0.45-0.46) 1.14 (1.13-1.15) 0.71 (0.70-0.72) 0.76 (0.75-0.77) 1.11 (1.10-1.11) <0.4 1.65 (1.64-1.66) 2.03 (2.02-2.04) 1.67 (1.66-1.69) 1.87 (1.87-1.88) 0.82 (0.81-0.83) 1.65 (1.64-1.66) 1.35 (1.34-1.35) <0.5 1.67 (1.66-1.67) 1.74 (1.74-1.74) 1.85 (1.84-1.85) 1.70 (1.70-1.71) 1.74 (1.73-1.75) 1.35 (1.34-1.35) 0.87 (0.87-0.87) <0.6 1.55 (1.55-1.55) 1.12 (1.12-1.12) 1.32 (1.32-1.33) 1.33 (1.33-1.34) 1.34 (1.34-1.34) 0.93 (0.93-0.93) 0.76 (0.76-0.76) <0.7 1.23 (1.23-1.23) 0.91 (0.91-0.91) 1.03 (1.03-1.04) 1.08 (1.08-1.08) 0.98 (0.97-0.98) 0.81 (0.81-0.81) 0.74 (0.74-0.74) 0.5≤ &≤0.7 0.83 (0.83-0.83) 1.18 (1.1-1.18) 1.02 (1.02-1.03) 0.97 (0.96-0.97) 1.07 (1.07-1.07) 1.30 (1.30-1.30) 1.37 (1.37-1.37) >0.7 0.96 (0.96-0.96) 1.02 (1.03-1.03) 0.99 (0.99-0.99) 0.98 (0.98-0.98) 1.00 (1.00-1.00) 1.05 (1.05-1.05) 1.11 (1.10-1.11) >0.8 0.98 (0.97-0.98) 1.11 (1.11-1.11) 1.05 (1.05-1.05) 1.02 (1.02-1.02) 1.05 (1.05-1.05) 1.16 (1.16-1.16) 1.26 (1.26-1.26) >0.9 1.05 (1.05-1.05) 1.29 (1.29-1.29) 1.15 (1.15-1.15) 1.12 (1.12-1.12) 1.13 (1.13-1.13) 1.38 (1.38-1.38) 1.48 (1.48-1.48) >1.0 1.19 (1.19-1.19) 1.61 (1.61-1.61) 1.39 (1.38-1.39) 1.31 (1.31-1.31) 1.32 (1.32-1.32) 1.71 (1.71-1.72) 1.76 (1.76-1.76) >1.1 1.40 (1.40-1.40) 2.10 (2.10-2.10) 1.68 (1.68-1.68) 1.60 (1.60-1.60) 1.52 (1.52-1.52) 2.13 (2.13-2.13) 2.22 (2.22-2.22) >1.2 1.73 (1.73-1.73) 2.72 ( 2.71-2.72) 2.20 (2.20-2.20) 1.99 (1.99-1.99) 1.88 (1.88-1.88) 2.74 (2.74-2.74) 2.56 (2.56-2.56) >1.3 2.17 (2.16-2.17) 3.34 (3.34-3.35) 2.77 (2.76-2.77) 2.48 (2.48-2.48) 2.30 (2.30-2.30) 3.27 (3.27-3.28) 2.83 (2.83-2.84) >1.4 2.87 (2.87-2.87) 4.35 (4.34-4.35) 4.01 (4.00-4.02) 3.20 (3.20-3.20) 3.18 (3.17-3.18) 4.18 (4.17-4.18) 3.19 (3.18-3.19) >1.5 3.46 (3.46-3.47) 5.28 (5.27-5.29) 5.53 (5.52-5.55) 3.78 (3.77-3.78) 4.16 (4.15-4.16) 4.70 (4.69-4.71) 3.47 (3.46-3.47) >1.6 4.40 (4.39-4.40) 6.17 (6.16-6.19) 7.05 (7.03-7.08) 4.67 (4.66-4.68) 4.84 (4.82-4.85) 5.53 (5.51-5.55) 4.18 (4.16-4.19) >1.7 5.49 (5.47-5.50) 7.13 (7.11-7.15) 7.92 (7.88-7.95) 5.85 (5.84-5.86) 5.85 (5.83-5.87) 7.48 (7.45-7.51) 4.82 (4.80-4.83) >1.8 5.73 (5.70-5.75) 6.98 (6.96-7.00) 8.79 (8.74-8.83) 5.80 (5.79-5.82) 6.03 (6.00-6.05) 7.13 (7.10-7.17) 4.78 (4.76-4.80) data are presented with 95% confidence interval. +lr for admission increased with increasing msi values in each age group; however, elderly patients ≥65 years demonstrated the lowest +lr of 4.81 (95% ci 4.79-4.83) for msi>1.7 compared to +lrs of 5.85 (95% ci 5.83-5.87) and 7.48 (95% ci 7.45-7.51) in those 18-44 years old and 45-64 years old, respectively. an explanation to this finding could be the use of antihypertensives in elderly, including beta blockers that may blunt hr response, which results in lower msi values. another explanation could be the lower threshold of admitting elderly patients regardless of msi due to polypharmacy and multiple comorbidities. our study showed promising results and the findings can be used in the general ed population, to help identify sick patients and allow the ed team to allocate resources effectively and efficiently. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. hamade et al. 6 5. limitations our study has certain limitations. this was a retrospective study that used a representative national data, of which 41,552,879 (7.23 %) encounters were excluded due to missing data. the cohort was not uniform in terms of diagnosis, and thus patients presenting with disease states that do not affect stroke volume might have potentially skewed our results and generated a different msi threshold than described in previous studies. as data was not available to us, we also could not account for pre-ed interventions, such as crystalloid and blood product administration, nor could we account for medication profiles, both of which could have potentially affected our results; specifically, the use of beta blockers altering the heart rate, or oral peripheral vasoconstrictors and other antihypertensive medications that would affect physiological responses to illness, thus affecting msi values. we could not account for the way map and bp were measured non-invasively by using automated machines such as oscillometry or manually via sphygmomanometer, which sometimes yields different values (13). data on serial vital signs was not available to study serial msi measurements, which can have significant prognostic reliability. we also did not have data regarding level of care upon admission. our study derived msi thresholds for all ed comers and more research is needed in specific patient populations, such as trauma and sepsis, as different msi threshold maybe derived. in addition, our research focused on one compound variable -the msiand future studies are needed conducting multivariate analysis including the msi in order to construct a more comprehensive best fit model. finally, mortality could have been a result of different complications during the hospital course, and not a direct effect of the presenting ed complaint, but the limitation is due to our date set. 6. conclusion our large nationally representative retrospective study of all adult ed patients suggests that an initial msi >1.7 in the general adult ed population is an important predictor of admission and in-hospital mortality. further studies on msi are needed in various specific patient populations to further assess its relationship to the current triage systems, its impact on resource utilization and allocation in the ed, and on the decision making regarding the level of care of the admitting unit. 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest none. 7.3. fundings and supports none. 7.4. authors’ contribution bh, jdb, and naj conceived the study. jdb and naj obtained irb approval. bh, jdb, and naj designed the study. 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benson sm, bilonick ra, wu wc, et al. trends in acute myocardial infarction hospitalization rates for us states in the cdc tracking network. plos one. 2013;8(5):e64457. 32. ramirez l, kim-tenser ma, sanossian n, cen s, wen g, he s, et al. trends in acute ischemic stroke hospitalizations in the united states. j am heart assoc. 2016,11;5(5). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e41 or i g i n a l re s e a rc h using sodium bicarbonate during prolonged cardiopulmonary resuscitation in prehospital setting; a retrospective cross-sectional study thongpitak huabbangyang1, chunlanee sangketchon1∗, gotchagorn noimo2, korawee pinthong2, ketvipa saungun2, kaiwit bunta2, chomkamol saumok3 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. 3. division of emergency medical service and disaster, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. received: march 2023; accepted: april 2023; published online: 25 may 2023 abstract: introduction: although the 2020 american heart association (aha) guidelines recommend that sodium bicarbonate (sb) be avoided during routine cardiopulmonary resuscitation (cpr) a limited number of studies have examined the effects of sb injection during prolonged cpr (>15 min) in prehospital setting. the present study aimed to examine the effects of prehospital sb use during prolonged cpr on patients’ outcome. methods: in this retrospective crosssectional study adult patients aged >18 years who experienced a non-traumatic, out-of-hospital cardiac arrest (ohca) were compared regarding three outcomes, namely return of spontaneous circulation (rosc), rosc > 20 minute, and survival to discharge, based on receiving or not-receiving sb during cpr. results: 330 patients were divided into two equal groups of 165. the two groups had similar conditions regarding gender distribution (p = 0.729); mean age (p = 0.741); underlying diseases (p = 0.027); etiology of arrest (p = 0.135); the initial rhythm (p = 0.324); receiving normal saline solution (p = 1.000), epinephrine (p = 0.848), and atropine during cpr (p = 0.054); and using defibrillation (p = 0.324). those who received sb had 0.80 times greater likelihood for sustained rosc (adjusted odds ratio (or) = 0.80, 95% ci: 0.47–1.37, p = 0.415), 0.93 times greater likelihood for rosc at the scene (adjusted or = 0.93, 95% ci: 0.55–1.59, p = 0.798), and 0.34 times greater likelihood for survival to discharge (adjusted or = 0.34, 95% ci: 0.10–1.17, p = 0.087). conclusion: the present study demonstrated that prehospital sb use by ems during prolonged cpr did not improve rosc rate at the scene, sustained rosc, and survival to discharge. keywords: cardiopulmonary resuscitation; emergency medical services; treatment outcome; out-of-hospital cardiac arrest; sodium bicarbonate cite this article as: huabbangyang t, sangketchon c, noimo g, pinthong k, saungun k, bunta k, saumok c. using sodium bicarbonate during prolonged cardiopulmonary resuscitation in prehospital setting; a retrospective cross-sectional study. arch acad emerg med. 2023; 11(1): e41. https://doi.org/10.22037/aaem.v11i1.2002. 1. introduction sodium bicarbonate (sb) is the primary medication used as buffer therapy during cardiac arrest. previous researchers hypothesized that sb therapy corrected metabolic acidosis and could improve outcomes in cardiac arrest (1). during cardiac arrest, an imbalance in oxygen exchange occurs in the ∗corresponding author: chunlanee sangketchon; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok 10400, thailand. tel: +66 2-244-3000, email: chunlanee@nmu.ac.th, orcid: https://orcid.org/00000003-4509-1527. body, resulting in acidosis (2). observational studies on intensive care units reported that over 95% of cardiac arrest patients exhibited acidosis after return of spontaneous circulation (rosc), especially those receiving prolonged cardiopulmonary resuscitation (cpr) (3). moreover, available evidence suggests that low blood ph or acidosis after rosc significantly increased mortality rates in hospitals. similarly, one study showed that every 0.1-unit increase in ph from ph <7.2 promoted an increase in the likelihood of survival to discharge (4). sb has been widely used not only in context of inhospital medical services but also in prehospital emergency medical services (ems). a study found that sb use during cpr by ems significantly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 2 improved the outcomes of rosc (5). but, one study found that sb use was not associated with improved outcomes of rosc or increased rates of survival to discharge in cardiac arrest patients. in fact, mortality increased significantly, with several side effects of sb use having been noted during cpr, which included hypernatremia, alkalosis, and excess carbon dioxide production (6). a prospective randomized controlled trial (rct) comparing out-of-hospital cardiac arrest (ohca) patients treated with and without sb found that sb administration was not associated with the likelihood of favorable functional 30-day outcomes (7). therefore, the 2010, 2015, and 2020 american heart association guidelines for advanced cardiac life support do not recommend routine use of sb during cpr in cardiac arrest patients except in the presence of certain indications, namely pre-existing metabolic acidosis, hyperkalemia, and tricyclic antidepressant intoxication (8-10). previously studies had vigorously attempted to prove the efficacy of sb. one rct demonstrating the benefit of sb use in cardiac arrest patients requiring prolonged cpr (>15 min) found that sb use was significantly associated with increased rosc rates (11). present knowledge has suggested that prolonged cpr results in just a <1% or no chance for rosc, survival to discharge, and favorable outcomes (12). as such, prolonged resuscitation can trigger anxiety among health care personnel, including prehospital emergency medical staff, and has been associated with many factors. one previous study found that bystander cpr and initial shockable rhythm might be important factors causing prolonged cpr in cardiac arrest patients, particularly prehospitally (13). prevailing knowledge suggests that buffer therapy with sb by ems can be an option for treating ohca patients requiring prolonged cpr. however, such circumstances have some limitations, that is, blood gas testing cannot be performed and there is a current paucity in human studies examining the effects of sb in cases requiring prolonged cpr. no clear and concrete guidelines on rational sb use in ohca patients have been established, and empirical evidence supporting the prehospital use of sb has been lacking and there are limited resources and emergency medical staff. hence, the present study aimed to examine the effects of prehospital sb use during prolonged cpr (for >15 min) on sustained rosc (>20 min), rosc at the scene, and survival to discharge. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted at vajira emergency medical service (v-ems), vajira hospital, navamindradhiraj university, bangkok, thailand. patients with ohca, who underwent cpr were compared regarding rosc, rosc > 20 minute, and survival to discharge, based on receiving or not-receiving sb during cpr. v-ems is primarily responsible for providing ems to zone area one among a total of nine zone areas within bangkok and is dispatched by erawan center, bangkok, which maintains a network of six public and private hospitals within the 50 km2 area of responsibility with a population of 500,000 (14, 15). when responding to ohca patients in need of ems, v-ems dispatches one team at a time, which includes at least three staff comprising paramedics or emergency nurse practitioners (enps) as the operation team leader and emergency medical technicians. during each operation, paramedics or enps would follow off-line and on-line medical protocols under the emergency physicians’ orders. in cases involving cardiac arrest patients within the area, the 2020 american heart association (aha) guidelines were applied by paramedics or enps. everyone passed advanced cardiovascular life support training (10). this study was conducted in accordance with the tenets of the declaration of helsinki 1975 and its later revisions. our study protocol was approved by the institutional review board of the faculty of medicine, vajira hospital, navamindradhiraj university (coa no. 216/2565). the requirement for informed consent was waived due to the retrospective nature of our study and anonymity of all patient data. 2.2. participants data of adult ohca patients aged >18 years were collected from ems patient care reports coded as symptom group 6 (cardiac arrest) based on the thailand emergency medical triage protocol and criteria-based dispatch (cbd) from 1 january 2019 to 31 december 2020 (2 years). ohca patients to whom the v-ems unit was dispatched were selected using simple random sampling. these reports were completed by the v-ems unit. patients who had rosc within 15 min, had incomplete or missing data, were evaluated as dead by a team leader and required no resuscitation, had a do-not-resuscitate order, had a cardiac arrest outdoors, had suffered an ohca during transfer, in which cpr was started at the scene and continued during transfer to the hospital, and had termination of resuscitation at the scene were excluded from the study. 2.3. data gathering data of ohca patients were collected from ems patient reports, a standard form recording advanced ems procedures performed by bangkok ems (erawan center), with the bangkok advanced emergency operation unit utilizing a similar form. in particular, this form contained data on ems operation units, patients, and all treatments performed by ems teams, including dispatchers and paramedics or enps operating at the scene. these data were required to deterthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e41 mine the remuneration of ems operation units. data on survival to discharge were extracted from the electronic medical records (emr) at vajira hospital. all data were collected and entered into a microsoft excel spreadsheet. data obtained from the electronic medical records comprised: 1) the general characteristics of ohca patients including gender, age, underlying disease, location type, cause of cardiac arrest, witnessed collapse, bystander cpr, initial rhythm, defibrillation, advanced airway, prehospital intravenous (iv ) fluids, medication during cpr, total cpr time (min), time from cpr to sb (min), and sb amount (meq/ml), and 2) study outcomes including sustained rosc (>20 min), rosc, and survival to discharge. patients were followed up every 30 days by a principal investigator (th) to determine the survival to discharge outcomes. in-hospital outcomes were determined from the emr of vajira hospital. 2.4. definitions rosc indicates a return of circulation wherein the heart is able to sufficiently pump blood throughout the body, which can be characterized by a palpable pulse and measurable blood pressure at the scene (1, 15). sustained rosc (>20 min) indicates a return of circulation wherein the heart is able to sufficiently pump blood throughout the body, which can be characterized by a palpable pulse and measurable blood pressure at the scene that continued for 20 min (1). survival to discharge indicates the patient’s status after 30 days starting from the first day the patient suffered an ohca (1). symptom group 6 indicates ohca according to the emergency level screening system, which can be classified as cbd 6, severity level–critical (red) 6 critical 1 or 6 red 1, indicating cardiac arrest including unconsciousness, apnea, or pulselessness (15). total cpr time (min) indicates the duration from the first medical contact (fmc) to the end of cpr determined from the ems patient care report. time from cpr to sb (min) indicates the duration from the fmc to sb injection among ohca patients determined from the ems patient care report. witnessed collapse or witnessed arrest means cardiac arrest with witness, which probably is layperson or medical personnel witnessing the event during a patient having sudden cardiac collapse (10). 2.5. outcomes measurement the primary outcome was effects of prehospital sb use during prolonged cpr on sustained return of spontaneous circulation (rosc) (>20 min) at the scene, and the secondary outcome was survival to discharge. 2.6. statistical analysis we estimated the sample size needed to test two independent proportions (16). sample size calculation was based on statistical data presented in a previous study by weng et al. (1), who reported sustained rosc (>20 min) rates of 6.7% (p1 = 0.067) and 19.4% (p2 = 0.194) for those with and without prehospital sb administration during cpr, respectively. assuming a 1:1 ratio in the sample size of the compared groups, our sample size calculation determined that at least 147 patients per group were needed. after adding 10% of the sample size using the formula nnew = 147/(1–0.1), we determined that at least 163 patients per group were required. therefore, the final sample size consisted of 165 patients per group or a total of 330 patients. descriptive analysis was performed to determine the distribution of variables. continuous variables are presented as mean ± standard deviation (sd), whereas categorical variables are presented as frequencies and proportions. differences between the two studied groups were evaluated using the independent t-test or mann–whitney u test for numeric variables and the chi-square test or fisher’s exact test for categorical variables. to compare the groups with and without prehospital sb administration during cpr, the chi-squared test or fisher’s exact test were used depending on the appropriateness of data. multivariate analysis using multiple logistic regression was used to determine the effects of prehospital sb use during prolonged cpr on sustained rosc, rosc at the scene, and survival to discharge, reporting the odds ratios (or) and 95% confidence intervals for the same. ibm spss statistics for windows version 28.0 (armonk, ny, usa: ibm corp.) was used for all statistical analyses, with a p value of ≤.05 indicating statistical significance. 3. results 3.1. baseline characteristics of studied cases 330 patients with ohca were divided into two groups based on prehospital sb use (165 patients each). the mean time from cpr to sb was 18.92 ± 7.51 minutes and the mean amount of sb was 54.48 ± 18.72 meq/ml. table 1 compares the baseline characteristics of studied cases between the two groups. the two groups had similar conditions regarding gender distribution (p = 0.729); mean age (p = 0.741); underlying diseases (p = 0.027); etiology of arrest (p = 0.135); the initial rhythm (p = 0.324); receiving normal saline solution (p = 1.000), epinephrine (p = 0.848), and atropine during cpr (p = 0.054); and using defibrillation (p = 0.324). 53.3% and 41.8% had witnesses arrest (p = 0.036), and 55.2% and 35.2% obtained bystander cpr, in the sb and non-sb this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 4 table 1: comparing the baseline characteristics of patients with out of hospital cardia arrest (ohca) based on receiving or not receiving sodium bicarbonate (sb) characteristic total (n = 330) p value sb (n = 165) non-sb(n=165) gender male 106 (64.2) 109 (66.1) 0.729 female 59 (35.8) 56 (33.9) age (year) mean ± sd 64.44 ± 17.88 65.08 ± 17.68 0.741 underlying disease no 65 (39.4) 85 (51.5) 0.027 yes 100 (60.6) 80 (48.5) location of cardiac arrest non-public 131 (79.4) 133 (80.6) 0.783 public 34 (20.6) 32 (19.4) cause of cardiac arrest presumed cardiac etiology 128 (77.6) 134 (81.2) respiratory 33 (20.0) 21 (12.7) aoc 1 (0.6) 5 (3.0) hypoglycemia 3 (1.8) 2 (1.2) 0.135 seizure 0 (0.0) 1 (0.6) ugib 0 (0.0) 1 (0.6) unknown 0 (0.0) 1 (0.6) witnessed arrest no 77 (46.7) 96 (58.2) 0.036 yes 88 (53.3) 69 (41.8) bystander cpr no 74 (44.8) 107 (64.8) <0.001 yes 91 (55.2) 58 (35.2) initial rhythm asystole 111 (67.3) 122 (73.9) ventricular fibrillation 27 (16.4) 25 (15.2) 0.324 pea 25 (15.2) 18 (10.9) pulseless vt 2 (1.2) 0 (0.0) defibrillation no 121 (73.3) 139 (84.2) 0.015 yes 44 (26.7) 26 (15.8) advanced airway management ett 144 (87.3) 107 (64.8) <0.001 bvm 11 (6.7) 54 (32.7) lma 10 (6.1) 4 (2.4) prehospital iv fluid nss 161 (97.6) 161 (97.6) 1.000 rls 3 (1.8) 3 (1.8) acetar 1 (0.6) 1 (0.6) medication during cpr epinephrine 165 (100) 165 (100.0) na amiodarone 16 (9.7) 14 (8.5) 0.848 atropine 8 (4.8) 2 (1.2) 0.054 calcium gluconate 63 (38.2) 9 (5.5) <0.001 glucose 23 (13.9) 8 (4.8) 0.005 total cpr time (minute) mean ±sd 33.81 ± 13.25 25.08 ± 12.40 <0.001 data are presented as mean ± standard deviation (sd) or frequency (%). na: data not applicable; pea: pulseless electrical activity; vt: ventricular tachycardia; ett: endotracheal tube; bvm: bag valve mask; lma: laryngeal mask airway; aoc: alteration of consciousness; cpr: cardiopulmonary resuscitation; ugib: upper gastrointestinal bleeding; iv: intravenous; nss: normal saline solution; rls: ringer’s lactated solution. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e41 table 2: comparing the studied outcomes between patients receiving and not receiving sodium bicarbonate (sb) outcomes sb (n = 165) non-sb (n = 165) odds (95% ci) p value rosc at the scene no 115 (69.7) 110 (66.7) 0.8 7 (0.55–1.38) 0.555 yes 50 (30.3) 55 (33.3) sustained rosc (>20 min) no 122 (73.9) 124 (75.2) 1.07 (0.65–1.75) 0.800 yes 43 (26.1) 41 (24.8) survival to discharge no 140 (84.8) 132 (80.0) yes 4 (2.4) 9 (5.5) 0.42(0.13–1.39) 0.145 unknown 21 (12.7) 24 (14.5) data are presented as frequency (%). ci: confidence interval; rosc: return of spontaneous circulation. groups, respectively (p < 0.001). most patients in the sb and non-sb groups were managed using endotracheal tube (ett) (87.3% and 64.8%, respectively; p < 0.001) and among the same groups, 38.2% and 5.5% received calcium gluconate (p < 0.001), and 13.9% and 4.8% received glucose during cpr, respectively (p = 0.005). the mean total cpr time was 33.81 ± 13.25 and 25.08 ± 12.40 minutes in the sb and non-sb groups, respectively (p < 0.001). 3.2. comparing the studied outcomes between groups table 2 compares the studied outcomes between patients receiving and not receiving sb. among the patients in the sb and non-sb groups, 30.3% and 33.3% exhibited rosc at the scene, respectively (p = 0.555). the rate of sustained rosc was 26.1% and 24.8% (p = 0.800), whereas the rate of survival was 2.4% and 5.5% (p = 0.145) in sb and non-sb cases, respectively). 3.3. chance of rosc univariate analysis using simple logistic regression analysis showed that the sb group had 0.87 times greater chance for rosc at the scene (crude or = 0.87, 95% ci: 0.55–1.38, p = 0.555). multivariate analysis using multiple logistic regression was performed including confounders that were found to be significantly (p < 0.05) associated with rosc at the scene in univariate analysis (which included: location of arrest, witness arrest, initial rhythm, defibrillation, atropine, and total cpr time). the analysis showed that the sb group had 0.93 times greater likelihood of rosc at the scene (adjusted or = 0.93, 95% ci: 0.55–1.59, p = 0.798). 3.4. likelihood of sustained rosc similarly, univariate analysis using simple logistic regression showed that the sb group had 1.07 times greater likelihood of sustained rosc (crude or = 1.07, 95% ci: 0.65–1.75, p = 0.800). multivariate analysis using multiple logistic regression, entering confounders that were significantly (p < 0.05) associated with sustained rosc (which included: witnesses arrest, initial rhythm, and advanced airway) showed that the sb group had 0.80 times greater likelihood of sustained rosc (adjusted or = 0.80, 95% ci: 0.47–1.37, p = 0.415). 3.5. likelihood of survival to discharge univariate analysis using simple logistic regression showed that the sb group had 0.42 times greater likelihood of survival to discharge (crude or = 0.42, 95% ci: 0.13–1.39, p = 0.156). multivariate analysis using multiple logistic regression, entering confounders that were significantly (p < 0.05) associated with survival to discharge during univariate analysis (which included: initial rhythm and defibrillation) showed that the sb group had 0.34 times greater likelihood of survival to discharge (adjusted or = 0.34, 95% ci: 0.10–1.17, p = 0.087). 4. discussion our main finding showed that sb use during prolonged cpr did not improve sustained rosc. notably, 26.1% of ohca patients receiving sb had sustained rosc, whereas 24.8% of those who did not receive sb had the same. although the group who used sb use showed greater rates of sustained rosc, the difference was not statistically significant (p = 0.800), suggesting that sb administration by ems did not increase the rate at which patients achieved rosc at the scene. surprisingly, our finding showed that the group with sb use had lower rates of survival to discharge than did those without sb administration (2.4% vs. 5.5%, respectively). the results of the present study were consistent with those reported in a previous study with a small sample size, which showed that sb administration, as buffer therapy during prolonged cpr, did not improve sustained rosc and survival to discharge. unexpectedly, the same study showed that among those who received sb injection, none showed survival to discharge (1). moreover, a previous pilot study, which was an rct comparing the administration of sb and placebo in carthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 6 diac arrest patients at the emergency department with severe metabolic acidosis during prolonged cardiopulmonary resuscitation, showed that sb use significantly affected ph values and helped modify the acid–base balance of the blood. however, the mentioned study did not find a significant difference in sustained rosc (4.0% vs. 16.0%, p = 0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, p = 1.000) between the sb and placebo groups (17). recently, two systematic review and meta-analysis studies evaluating the effects of sb on rosc and survival-todischarge rates both concluded that sb use was not associated with improvement in rosc or survival-to-discharge rate, consistent with our findings. furthermore, the same studies found that sb administration was associated with decreased rates of sustained rosc and survival-to-discharge (6, 18). however, some previous studies have shown findings contrary to those presented herein, such as the populationbased study using data of ohca patients at an emergency department in taiwan that had been retrospectively collected for 16 years. accordingly, the mentioned study showed that sb administration during resuscitation at the emergency department was positively associated with survival to hospital admission (adjusted or: 4.47; 95% ci: 3.82–5.22, p < 0.001) (19). another study on cardiac arrest patients with non-shockable rhythm, including asystole and pulseless electrical activity (pea), showed that sb use helped improve rosc and significantly increased rate of survival to discharge from a hospital (20). in addition, one study on sb use during prolonged cardiopulmonary resuscitation at the emergency department found that determining the bicarbonate levels from blood gas tests and administering the appropriate amount of sb that accounted for body weight (1 meq/kg) could increase the rates of rosc within 20 min (21). several explanations for the present results may be provided. firstly, the increased rates of sustained rosc and survival to discharge in the non-sb group might be explained by the shorter total cpr time in the non-sb group than in the sb group (22.66 ± 13.48 vs. 30.24 ± 12.79 min, respectively; p < 0.001). this could have been due to the failure of the ems to identify the cause of the arrest in patients who had no rosc and needed to receive prolonged cpr, which could have resulted in more sb administration. however, in the present study, sb administration during prolonged cpr did not improve the rates of rosc at the scene, sustained rosc, and survival to discharge. therefore, we do not recommend sb use during prolonged cpr in the prehospital setting. when prolonged cpr is required, the ems should focus on providing high-quality cpr and identifying the cause of the arrest, which are more important than sb administration. regarding the context of ems in the present study area, the decision for prolonged cpr depended on several factors, such as the cause of the arrest, relatives’ decision regarding cpr duration, cardiac rhythm, and unwitnessed or witnessed arrest, among others. the 2010, 2015, and 2020 aha guidelines do not recommend routine use of sb during cpr in cardiac arrest patients, unless there is medical indication (8-10). the 2020 aha guidelines used in the present study recommend using sb only in patients whose cause of arrest could be determined, those with sodium channel blocker toxicity (e.g., tricyclic antidepressants and diphenhydramine), and those receiving adjunctive therapy for suspected hyperkalemia (10). nonetheless, the 2021 european resuscitation council guidelines still recommended sb use in cases requiring prolonged unresponsive resuscitation, together with efficient rescue breathing to decrease acidosis. guideline recommendations regarding sb use still need to be discussed and prospectively studied, especially sb use in the prehospital context by ems (22). secondly, the vicious cycle of metabolic acidosis due to cardiac arrest and prolonged cpr, resulting in delayed cardiac response and delayed rosc, must be addressed. limited approaches for prehospital management are available, including buffer therapy with sb, ett, or laryngeal mask airway (lma) insertion and proper rescue breathing. the present study found that the rate of rosc was greater in patients receiving sb with ett and lma insertion than in those receiving rescue breathing by bvm. thirdly, one previous study reported that sb had multiple side effects, which probably increased the severity level of the cardiac arrest. the reason why only a limited number of patients achieved sustained rosc, rosc at the scene, and survival to discharge could probably be explained by the side effects of sb use, which include alkalosis, hypernatremia, excess production of carbon dioxide, central venous acidosis with inactivation of epinephrine administration, and compromised coronary flow (23). available evidence to date suggests that sb needs to be used cautiously and rationally in ohca patients to reduce disadvantages due to excessive sb use. however, the 2020 aha guidelines specify the amount of sb to be used based on body weight (meq/kg) (10). nonetheless, in the context of actual ems practice, determining the actual body weight of ohca patients is considerably challenging and might lead to medication dosage errors. 5. limitations firstly, the present study was a retrospective single-center study with two data sources: 1) from ems patient care reports and 2) from the electronic medical records. despite our attempts to maintain neutrality where possible, the risk of selection bias cannot be completely eliminated. secondly, no blood gas test results were available in the present study given that no equipment for blood gas point-of-care testing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e41 were available for the management of cardiac arrest patients at the scene, unlike studies at the emergency department. thirdly, some confounding factors associated with the target outcomes might have been overlooked. only data on prehospital management were analyzed in the present study without considering essential data from the emergency department or intensive care unit. fourthly, data on survival to discharge had several unknown aspects regarding the patients’ last status, such as neurological evaluation or cerebral performance category (cpc) score after hospital discharge. fifthly, for the study area, off-line protocol in management of ohca patients allowed paramedics or enps to be able to administer sb in patients with prolonged cpr. if the study results were applied in other areas, there would probably be limitations regarding generalizability (external validity) of the study results. this might include capacity of the operating team, indications and discretion of clinical decision of cpr commander about decision using sb. lastly, data for ohca patients in the area were not recorded and collected using the utstein ohca template. 6. conclusion the present study demonstrated that prehospital sb use by ems during prolonged cpr did not improve the likelihood of sustained rosc, rosc at the scene, and survival to discharge. it seems that, in cases requiring prolonged cpr, high-quality cpr and determination of the cause of arrest, focusing on the 5 h’s and 5 t’s that may cause cardiac arrest, should be emphasized over buffer therapy. 7. declarations 7.1. acknowledgments the authors were grateful to navamindradhiraj university research fund, paramedics at v-ems, faculty of medicine vajira hospital, navamindradhiraj university, for facilitating data collection and access in the present study, gawin tiyawat, md., chief of department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, and chunlanee sangketchon, md., deputy dean of faculty of science and health technology, navamindradhiraj university, for support and suggestions in the research development and aniwat berpan, md. for suggestions on english for the present study. 7.2. conflict of interest the authors have no conflicting interests to declare. 7.3. fundings this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution conceptualization: thongpitak huabbangyang, chunlanee sangketchon, chomkamol saumok, gotchagorn noimo, korawee pinthong, ketvipa saungun and kaiwit bunta; methodology: thongpitak huabbangyang, gotchagorn noimo, korawee pinthong, ketvipa saungun and kaiwit bunta; validation: thongpitak huabbangyang and chunlanee sangketchon; formal analysis: thongpitak huabbangyang; investigation: thongpitak huabbangyang, gotchagorn noimo, korawee pinthong, ketvipa saungun and kaiwit bunta; resources: thongpitak huabbangyang and chunlanee sangketchon; data curation: thongpitak huabbangyang; writing – original draft: thongpitak huabbangyang; writing review & editing: thongpitak huabbangyang and chunlanee sangketchon; visualization: thongpitak huabbangyang; supervision: thongpitak huabbangyang and chunlanee sangketchon; project administration: thongpitak huabbangyang; funding acquisition: thongpitak huabbangyang. all authors read and approved final version. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. 7.6. using artificial intelligent chat bots none. references 1. weng y-m, wu s-h, li w-c, kuo c-w, chen s-y, chen j-c. the effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation. am j emerg med. 2013;31(3):562-5. 2. spencer c, butler j. survival after cardiac arrest and severe lactic acidosis (ph 6.61) due to haemorrhage. emerg med j. 2010;27(10):800-1. 3. jamme m, ben hadj salem o, guillemet l, dupland p, bougouin w, charpentier j, et al. severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome. ann intensive care. 2018;8(1):62. 4. carr c, carson ka, millin mg. acidemia detected on venous blood gas after out-of-hospital cardiac arrest predicts likelihood to survive to hospital discharge. j emerg med. 2020;59(4):e105-e11. this open-access article distributed 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navamindradhiraj university. j med assoc thai. 2021;104:1-9. 16. rosner b. fundamentals of biostatistics. 5th ed. duxbury: thomson learning; 2000. 17. ahn s, kim y-j, sohn ch, seo dw, lim ks, donnino mw, et al. sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. j thorac dis. 2018;10(4):2295-302. 18. alshahrani ms, aldandan hw. use of sodium bicarbonate in out-of-hospital cardiac arrest: a systematic review and meta-analysis. int j emerg med. 2021;14(1):21. 19. chen y-c, hung m-s, liu c-y, hsiao c-t, yang y-h. the association of emergency department administration of sodium bicarbonate after out of hospital cardiac arrest with outcomes. am j emerg med. 2018;36(11):1998-2004. 20. neth mr, daya mr. sodium bicarbonate therapy during out-of-hospital cardiac arrest: is presenting rhythm the key to benefit? resuscitation. 2023;182:109674. 21. kim j, kim k, park j, jo yh, lee jh, hwang je, et al. sodium bicarbonate administration during ongoing resuscitation is associated with increased return of spontaneous circulation. am j emerg med. 2016;34(2):225-9. 22. perkins gd, graesner j-t, semeraro f, olasveengen t, soar j, lott c, et al. european resuscitation council guidelines 2021: executive summary. resuscitation. 2021;161:1-60. 23. aufderheide tp, martin dr, olson dw, aprahamian c, woo jw, hendley ge, et al. prehospital bicarbonate use in cardiac arrest: a 3-year experience. am j emerg med. 1992;10(1):4-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e15 or i g i n a l re s e a rc h clinical risk factors of need for intensive care unit admission of covid-19 patients; a cross-sectional study farshid sharifi1, mohammad hossain mehrolhassani2, milad ahmadi gohari1, ali karamoozian1,3, yunes jahani1,3∗ 1. modeling in health research center, institute for futures studies in health, kerman university of medical sciences, kerman, iran. 2. health services management research center, institute for futures studies in health, kerman university of medical sciences, kerman, iran. 3. department of biostatistics and epidemiology, school of public health, kerman university of medical sciences, kerman, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: it could be beneficial to accelerate the hospitalization of patients with the identified clinical risk factors of intensive care unit (icu) admission, in order to control and reduce covid-19-related mortality. this study aimed to determine the clinical risk factors associated with icu hospitalization of covid-19 patients. methods: the current research was a cross-sectional study. the study recruited 7182 patients who had positive pcr tests between february 23, 2020, and september 7, 2021 and were admitted to afzalipour hospital in kerman, iran, for at least 24 hours. their demographic characteristics, underlying diseases, and clinical parameters were collected. in order to analyze the relationship between the studied variables and icu admission, multiple logistic regression model, classification tree, and support vector machine were used. results: it was found that 14.7 percent (1056 patients) of the study participants were admitted to icu. the patients’ average age was 51.25±21 years, and 52.8% of them were male. in the study, some factors such as decreasing oxygen saturation level (or=0.954, 95%ci: 0.944-0.964), age (or=1.007, 95%ci: 1.004-1.011), respiratory distress (or=1.658, 95%ci: 1.410-1.951), reduced level of consciousness (or=2.487, 95%ci: 1.721-3.596), hypertension (or=1.249, 95%ci: 1.042-1.496), chronic pulmonary disease (or=1.250, 95%ci: 1.006-1.554), heart diseases (or=1.250, 95%ci: 1.009-1.548), chronic kidney disease (or=1.515, 95%ci: 1.111-2.066), cancer (or=1.682, 95%ci: 1.130-2.505), seizures (or=3.428, 95%ci: 1.615-7.274), and gender (or=1.179, 95%ci: 1.028-1.352) were found to significantly affect icu admissions. conclusion: as evidenced by the obtained results, blood oxygen saturation level, the patient’s age, and their level of consciousness are crucial for icu admission. keywords: covid-19; intensive care units; logistic models; decision trees; support vector machine cite this article as: sharifi f, mehrolhassani mh, ahmadi gohari m, karamoozian a, jahani y. clinical risk factors of need for intensive care unit admission of covid-19 patients; a cross-sectional study. arch acad emerg med. 2023; 11(1): e15. https://doi.org/10.22037/aaem.v11i1. 1853. 1. introduction the current covid-19 pandemic caused by sars-cov-2 was first detected in december 2019 in wuhan, china (1, 2). as the number of new cases of covid-19 increased unexpectedly and the disease rapidly spread throughout the world, the world health organization declared a coronavirus pandemic on march 11, 2020 (3). to date, more than 640 million cases and 6.61 million deaths have been reported world∗corresponding author: yunes jahani; modeling in health research center, second floor, institute for futures studies in health building, kerman university of medical sciences, the beginning of the seven gardens road, kerman, iran. postal code/ p.o. box: 761-6913555, telephone number: 00983431325405, fax number: 00983432114278, email: u.jahani@kmu.ac.ir; yonesjahani@yahoo.com, orcid: https://orcid.org/0000-0002-6808-7101. wide (4). many covid-19 patients experience a relatively severe illness after a period of mild symptoms, and it is crucial to make quick and accurate diagnoses and to provide high-quality care to those who require admission to the intensive care unit (icu) (5, 6). according to previous studies, hospitalization in the icu plays a very important role in the treatment of covid-19 patients, as it has been proven to be very effective on reducing mortality among these patients (1). several studies have reported that gender, age, and underlying diseases are associated with severe disease and hospitalization in an icu. among patients with severe disease, acute kidney injury, acute respiratory distress syndrome, and heart diseases are the most commonly reported complications (710). based on the need and capacity of the medical center in various countries, the rate of covid-19 patients admitted to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index f. sharifi et al. 2 icu varies from 5% to 32% (11). as a result of the increased patient numbers and the lengthening of hospital stays, the hospital’s capacity to admit new patients is severely limited (12). the severely-limited capacity of the hospital to admit new patients may negatively affect patient care quality and also increase mortality rates (13). by identifying and classifying patients with high risks, a greater number of beds can be saved in the icu. studies have shown that accelerating the admission of patients with the identified major clinical risk factors for icu admission can reduce mortality rate. in addition to other nations, iran has also been affected by covid19. it has been estimated that approximately 7.55 million cases and more than 145,000 deaths have occurred since the first case of covid-19 was identified on february 18, 2020 (4, 14). it is noteworthy that approximately more than 500,000 people live in the city of kerman, located in southeastern iran (15). the city of kerman is one of those in iran where many patients require admission to the icu (16). more than half of the hospital’s capacity for icu admissions is used during ordinary times in kerman’s hospitals (17). similar to all hospitals and icus throughout the world, kerman’s hospitals and their icus face some limitations during a crisis like the covid-19 epidemic (18). identifying significant clinical risk factors in the early stages of this disease is crucial for predicting which patients will require admission to the icu (19). based on a patient’s disease symptoms, this study aimed to assist physicians in quickly identifying patients who will need icu admission. 2. methods 2.1. study design and settings the present study was a cross-sectional study conducted in afzalipour hospital, kerman, iran (700 beds), with focus on patients who had been hospitalized with covid-19 disease (20). the admission rules were defined by the guidelines published by the iranian ministry of health for managing covid-19 patients and based on a combination of clinical data (1). the required data were collected from electronic medical records of 7182 patients with a positive covid-19 pcr test, who were admitted to afzalipour hospital in kerman, iran, between february 23, 2020, and september 7, 2021, using the census method. research ethics committee of kerman university of medical sciences approved this study (no. ir.kmu.rec.1400.451). 2.2. participants the present study included all covid-19 patients who had been hospitalized for more than 24 hours and were diagnosed using sars-cov-2 nucleic acid rt-pcr (7, 21). patients with a negative pcr test for covid-19 were excluded from the study. also, hospitalized patients whose test status was unclear and were suspected to having covid-19 were excluded from the study. the patients were admitted to the icu directly or after being admitted to the general ward. 2.3. data collection for this study, the primary data source was electronic medical records from the medical care monitoring center (mcmc) system, which are frequently used in emergency situations. the patients’ data were accurately recorded in the mcmc system. the data for 10 patients were missing and they were excluded from the study. the dependent variable was receiving icu care, for patients who were hospitalized either in the icu or in the general ward (2). in this study, studied variables included age, gender, heart diseases, chronic kidney disease, chronic pulmonary disease, chronic liver disease, diabetes, cancer, hypertension, chronic neurological diseases, blood diseases, immunodeficiency (acquired or congenital), fever, myalgia, cough, chest pain, diarrhea, respiratory distress, vomiting and nausea, headache, loss of consciousness, smell or taste disorders, anorexia, seizures, dizziness, opium abuse, smoking, oxygen therapy, oxygen saturation level, and the time between the onset of symptoms and admission to the hospital. 2.4. statistical analyses in order to analyze the obtained data, the mean, standard deviation, frequency, and percentage were calculated. to control the effect of confounding variables, univariate and multiple logistic regression analyses were run and the effect of each variable was evaluated by adjusting for other variables. at first, univariate regression was performed, and variables with p-values less than 0.2 were considered as important and then added to multiple regression model. finally, p-values less than 0.05 were used to identify significant variables in the multiple logistic regression model and the backward approach. additionally, the odds ratios and 95% confidence intervals were reported (22, 23). the classification and regression trees (cart) model was used to classify the investigated variables, identify specific icu admission groups, and evaluate the interaction between the variables (24). a tree model was built with 10-fold crossvalidation, with 100 cases in the parent node and 50 subjects in the child node, and 10 maximum levels for the classification and regression trees model (cart) (25). the misclassification cost for patients who were wrongly admitted to the general ward instead of the icu was 5 times more than patients admitted to the icu instead of the general ward. therefore, it was considered that an effective strategy to solve the imbalanced classification problem is to maximize the sum of sensitivity and specificity (26, 27). moreover, support vecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e15 tor machine method was used to investigate and control the non-linear effect of confounding variables and separation of the variables affecting hospitalization in the icu. support vector machine method provides a powerful separator margin among classes using the kernel trick and converting the data into another dimension. this study used the radial basis function (rbf) as the kernel, and 10-fold cross-validation was applied to estimate model parameters (28, 29). afterward, the accuracy of support vector machine model and the importance of each variable regarding icu admission were determined (30). 2.5. sensitivity and specificity of models the data in this study were validated using the k-fold validation method. in the k-fold method, the data are divided into k subsets. besides, each sample is used once for validation and k-1 times for training. this process is repeated k times and all the data are used once for validation. finally, the average of these k validation times is reported. k was equal to 10 in the present study (31). accuracy, sensitivity, and specificity of the model was evaluated by comparing the prediction of the model regarding patients’ need for icu hospitalization with the reality (32). in the present study, descriptive analysis, univariate and multiple logistic regression, and classification tree model were conducted using spss.25 software and analysis of support vector machine was done using r software packages (caret and e1071). 3. results 3.1. patient characteristics the current study recruited 7,182 covid-19 patients with the mean age of 51.25 ± 21.00 (range: 0.02 (7 days)-102) years (52.8% male). the number of the patients admitted to the icu was 1056 (14.7%). among the patients, 413 (5.8%) cases were smokers and 898 (12.5%) cases were opium abusers. there were 1211 (16.9%) patients with hypertension, 976 (13.6%) patients with diabetes, 694 (9.7%) patients with heart diseases, and 608 (8.5%) patients with chronic pulmonary disease. the most prevalent signs and symptoms of these patients were respiratory distress with 4952 (69.0%), fever with 3426 (47.7%), and cough with 3603 (50.2%) cases. oxygen therapy was provided to 5684 (71.9%) of the hospitalized patients. according to this analysis, the patients were hospitalized at an average oxygen saturation level of 90.51±5.61 percent, and the time from the onset of symptoms to hospitalization was 5.7±3.59 days. table 1 shows the association between studied clinical variables with need for icu admission. 3.2. multiple logistic regression analysis of clinical risk factors for icu admission table 2 shows the results of multiple regression analysis of independent clinical risk factors of covid-19 patients’ need for icu admission. in multiple logistic regression, male cases had 1.179 times the odds of being admitted to the icu compared to females (or=1.179, 95%ci:1.028-1.352). in addition, being admitted to the icu was associated with age (or=1.007, 95%ci: 1.004-1.011). patients with heart diseases (or=1.250, 95%ci=1.009-1.548), chronic pulmonary disease (or=1.250, 95%ci=1.006-1.554), chronic kidney disease (or=1.515, 95%ci=1.111-2.066), hypertension (or=1.249, 95%ci=1.042-1.496), and cancer (or=1.682, 95%ci=1.130-2.50) had higher odds of being admitted to the icu. there was a higher chance of admission to the icu among the patients with signs and symptoms of loss of consciousness (or=2.487, 95%ci=1.721-3.596), seizures (or=3.428, 95%ci=1.615-7.274), respiratory distress (or=1.658, 95%ci=1.410-1.951), and a decrease in oxygen saturation level (or=0.954, 95%ci=0.944-0.964). moreover, the patients who had myalgia (or=0.847, 95%ci=0.7330.978), cough (or=0.827, 95%ci=0.722-0.949), diarrhea (or=0.727, 95%ci=0.561-0.941), headache (or=0.708, 95%ci=0.593-0.844), and smell or taste disorders (or=0.622, 95%ci=0.474-0.816) had a lower chance of being admitted to the icu. the total sensitivity and specificity of the model were maximized with a cut point of 0.145 in predicted probability of receiving icu care. multiple logistic regression model had 62.4% (95%ci=59-65) accuracy, 59.7% (95%ci=51.2-68.2) sensitivity, and 62.7% (95%ci=58.2-67.3) specificity. 3.3. classification tree the estimated tree model depicts a tree with five levels and eight nodes (figure 1). using the tree structure, it was determined that oxygen saturation level, age, and level of consciousness were the variables affecting icu hospitalization. there were four high-risk groups of patients admitted to the icu: the first group consisted of the patients with oxygen saturation levels less than 86.5%, the second group consisted of the patients younger than 0.196 years (72 days) whose oxygen saturation was greater than 86.5%, the third group consisted of patients older than 66.5 years with oxygen saturation level greater than 86.5%, and the fourth group consisted of the patients with a lowered level of consciousness aged between 0.196 and 66.5 years (figure 1). a cost of misclassification of 5 led both the sensitivity and specificity of the model to reach their maximum levels. classification tree model had an accuracy of 68.5% (95%ci=66.6-70.4), a sensitivity of 56.7% (95%ci=53.4-59.9), and a specificity of 70.5% (95%ci=68.0-73.0). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index f. sharifi et al. 4 table 1: the association between clinical characteristics of covid-19 cases with need for icu admission based on univariate analysis variables need for icu care or 95%ci p no yes age (year) mean ± sd 50.39±20.47 56.20±23.23 1.014 1.011-1.017 <0.001 gender female 2935 (86.6) 454 (13.4) 1 male 3191 (84.1) 602 (15.9) 1.220 1.069-1.391 0.003 underlying disease heart diseases 544 (78.4) 150 (21.6) 1.699 1.399-2.062 <0.001 chronic kidney disease 197 (75.8) 63 (24.2) 1.909 1.427-2.556 <0.001 chronic pulmonary disease 472 (77.6) 136 (22.4) 1.771 1.445-2.169 <0.001 chronic liver disease 67 (81.7) 15 (18.3) 1.303 0.742-2.290 0.357 diabetes 799 (81.9) 177 (18.1) 1.343 1.124-1.604 0.001 cancer 112 (75.7) 36 (24.3) 1.895 1.294-2.775 <0.001 hypertension 970 (80.1) 241 (19.9) 1.572 1.340-1.843 <0.001 blood diseases 33 (73.3) 12 (26.7) 2.122 1.093-4.122 0.02 immunodeficiency 22 (75.9) 7 (24.1) 1.851 0.789-4.345 0.157 chronic neurological diseases 139 (84.8) 25 (15.2) 1.044 0.679-1.607 0.843 fever 2980 (87.0) 446 (13.0) 0.772 0.676-0.881 <0.001 myalgia 2428 (87.3) 354 (12.7) 0.768 0.669-0.881 <0.001 cough 3123 (86.7) 480 (13.3) 0.801 0.703-0.914 0.001 chest pain 518 (87.1) 77 (12.9) 0.852 0.664-1.092 0.205 diarrhea 635 (89.4) 75 (10.6) 0.661 0.516-0.848 0.001 respiratory distress 4117 (83.1) 835 (16.9) 1.844 1.575-2.158 <0.001 vomiting and nausea 1269 (88.6) 164 (11.4) 0.704 0.589-0.840 <0.001 headache 1545 (89.3) 185 (10.7) 0.630 0.532-0.764 <0.001 loss of consciousness 91 (65.0) 49 (35) 3.227 2.226-4.596 <0.001 smell or taste disorders 568 (89.7) 65 (10.3) 0.642 0.492-0.837 0.001 seizures 24 (66.7) 12 (33.3) 2.92 1.457-5.862 0.003 anorexia 2277 (85.8) 376 (14.2) 0.935 0.816-1.017 0.331 dizziness 857 (83.7) 167 (16.3) 1.155 0.964-1.383 0.118 opium abuse 739 (82.3) 159 (17.7) 1.292 1.074-1.555 0.007 smoking 352 (85.2) 61 (14.8) 1.006 0.760-1.331 0.969 oxygen therapy 4896 (86.1) 788 (13.9) 0.739 0.634-0.860 <0.001 oxygen saturation (%) mean ± sd 90.88±5.4 88.4±7.8 0.945 0.936-0.954 <0.001 symptoms to admission (days) mean ± sd 5.80±3.49 5.679±4.14 0.990 0.972-1.009 0.296 data are presented as mean ± standard deviation (sd) or frequency (%). or: odds ratio; ci: confidence interval. 3.4. support vector machine a vector machine model was constructed after crossvalidation using the radial basis kernel function and parameters "sigma=0.0279, cost=2". in order to separate the classes and reduce data error, support vector machine used nonlinear variable separation as well as the best margin. as a result of using the vector machine model (figure 2), the variable importance graph indicated that oxygen saturation level had the greatest impact (100%) on the classification of hospitalized patients in icus and general wards followed by age (43.62%), respiratory distress (37.54%), and the decreased level of consciousness (29.72%). heart diseases, chronic pulmonary disease, and hypertension were found to have a significant effect on patients with about 18 to 20 percent, while myalgia, fever, vomiting and nausea, oxygen therapy, and chronic kidney disease were found to have a significant impact between 9 and 12 percent. in general, the importance of gender, seizures, diabetes, diarrhea, smell or taste disorders, and cancer variables ranged from 5 to 7 percent, while the importance of other variables was ranked to be lower. there was 99.8% (95%ci=99.6100.0) accuracy, 99.6% (95%ci=99.3-100.0) sensitivity, and 99.9% (95%ci=99.7-100.0) specificity for the support vector machine model. 4. discussion this study aimed to determine the clinical risk factors associated with covid-19 patients who require admission to the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e15 table 2: the association between clinical characteristics of covid-19 cases with need for icu admission based on multiple regression analysis variables or 95% ci p age (years) 1.007 1.004-1.011 <0.001 gender male 1.179 1.028-1.352 0.018 underlying disease heart diseases 1.250 1.009-1.548 0.042 chronic pulmonary disease 1.250 1.006-1.554 0.044 chronic kidney disease 1.515 1.111-2.066 0.009 cancer 1.682 1.130-2.505 0.010 hypertension 1.249 1.042-1.496 0.016 myalgia 0.847 0.733-0.978 0.024 cough 0.827 0.722-0.949 0.007 diarrhea 0.727 0.561-0.941 0.015 respiratory distress 1.658 1.410-1.951 <0.001 headache 0.708 0.593-0.844 <0.001 loss of consciousness 2.487 1.721-3.596 <0.001 smell or taste disorders 0.622 0.474-0.816 0.001 seizures 3.428 1.615-7.274 0.001 oxygen saturation (%) 0.954 0.944-0.964 <0.001 data are presented as mean ± standard deviation (sd) or frequency (%). or: odds ratio; ci: confidence interval. icu. by employing results of statistical methods, this crosssectional study identified some clinical risk factors associated with icu admission (33). one of the study’s strengths was the use of univariate and multiple logistic regression, classification tree, and support vector machine to develop a list of clinical risk factors that could be used to distinguish icu patients from general ward patients. according to the results of this study, amongst the demographic characteristics affecting hospitalization in the icu, gender is an important factor that is relevant and influential, and it was shown that the majority of patients admitted in the icu are men. age is one of the most significant clinical risk factors associated with icu hospitalization. as the age of patients increases, their chances of being hospitalized in the icu and experiencing a worsening of their disease’s condition also increase. even with acceptable oxygen saturation levels, newborns (less than 0.196 years old (72 days)) and the elderly (over 66.5 years old) require icu care. a meta-analysis of 59 studies involving 36,470 patients concluded that men and patients aged over 70 years old are more likely to be admitted to the icu compared to other patients (34). this study was consistent with the current study. since the results of the current study identified underlying diseases such as hypertension, chronic pulmonary disease, heart diseases, chronic kidney disease, and cancer as clinical risk factors, it can be said that patients with these underlying diseases experience a more severe form of covid19 and require special care. the most important underlying disease was hypertension. a meta-analysis of 30 original articles found that high blood pressure is significantly associated with increased mortality and need for intensive care, which is consistent with the results of this research (35). in some cases, certain signs and symptoms are strongly related to the possibility of admission to the icu. these factors may worsen a patient’s condition and also increase their need for intensive care. a low oxygen saturation level is considered to be the most significant risk factor in this study, and patients with low oxygen saturation levels must be admitted to icu. additionally, patients with oxygen saturation below 86.5% require immediate admission to the icu. in a previous study conducted on 641 patients at stony brook university hospital, it was found that patients with an oxygen saturation level of less than 92% are at high risk, and icu hospitalization was recommended due to the danger of low oxygen saturation levels and these findings are consistent with the findings of the present study (5). seizures, respiratory distress, and decreased level of consciousness are factors affecting the severity of the disease and the need for hospitalization in an icu. headache, myalgia, cough, diarrhea, and smell or taste disorders do not increase the severity of the disease, and most patients with these symptoms are admitted to the hospital’s general ward. the effects of diabetes, oxygen therapy, fever, vomiting, and nausea are not significant in multiple logistic regression model; whereas, they are considered to be important in the vector machine model. the reason for this difference may be related to the fact that vector machines consider non-linear relationships between variables, which can be used as a predictor of hospitalization icus (36). there is a higher chance of admission to the icu if the patient this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index f. sharifi et al. 6 figure 1: factors affecting patients’ intensive care unit (icu) admission according to the classification tree model. misclassification costs of the patients admitted to the general ward instead of the icu were five times more than the patients admitted to the icu instead of the general ward. so, in each node, the tree model predicts that the patient will be admitted to the icu if the proportion of admissions to the icu exceeds 16.6%. has an underlying disease like diabetes. a meta-analysis of 33 studies involving 16,003 patients confirmed that diabetes is significantly associated with covid-19-related mortality and disease severity, which is in agreement with our finding (37). symptoms such as fever, vomiting, and nausea do not worsen the disease, and patients with these symptoms are mostly adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e15 figure 2: the importance graph of the effective intensive care unit (icu) admission variables as calculated by the vector machine model. mitted to the general ward. patients with covid-19 who receive oxygen therapy are less likely to require admission to an icu. physicians can utilize this research results to be provided with a simple and accurate stratification tool that will enable them to manage patients with covid-19 and similar diseases in a timely manner (1). in general, the combined results of all the models revealed that a number of factors such as decreasing oxygen saturation level (the risk is higher for patients whose oxygen saturation level is less than 86.5%), aging (66.5 years and older), age under 72 days in infants, respiratory distress, decreased level of consciousness, hypertension, chronic pulmonary disease, heart diseases, chronic kidney disease, cancer, diabetes, and seizures are associated with severe type of illness and icu admission in covid-19 patients. additionally, these factors may guide physicians to make a better decision. for instance, if a patient aged 66.5 years or older is recommended to seek medical advice at the early stage of their illness, and if hospitalization is required, physicians should be aware of the high risk of severe disease in these groups (34). a combination of the results of the three models and the k-fold cross-validation increased the external validity of the study, and the comparison of model accuracy revealed that logistic model accuracy was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index f. sharifi et al. 8 62.7 percent, classification tree model accuracy was 64.3%, and support vector machine model accuracy was 99%. support vector machine model was the most accurate one. for clinical researchers, predicting covid-19 patients’ hospitalization in the icu is essential. accordingly, it is better to use the support vector machine model, which is more accurate. researchers should use classification tree if they need a simple algorithm for classifying the hospitalization of covid19 patients. in order to examine the association among the variables and severity of covid-19 disease and hospitalization in the icu, it is recommended to use logistic regression model(33). 5. limitations the type of treatment and different strains of covid-19 have changed over time and these may affect receiving or not receiving intensive medical care. these two variables were not addressed in this study. thus, they may cause bias and reduce the generalizability of the findings to the community. accordingly, they need to be addressed in future studies. it is possible that additional confounding factors exist that we have not included in the models. the criteria for admission of patients in icu of different hospitals are different, which it may affect the generalizability of the result. additionally, this study only focused on some clinical variables and laboratory data of hospitalized patients were unavailable, which it is recommended to consider them for future research. 6. conclusions the results of our study showed that clinical risk factors such as hypertension, chronic pulmonary disease, heart disease, chronic kidney disease, cancer, diabetes, seizures, and gender were predictors of patients’ admission to the icu, but oxygen saturation level, increasing age, respiratory distress, and reduced level of consciousness were identified as independent predictors of need for icu admission among covid-19 patients. the results of this study can help physicians and hospital staff to assign timely special care services to patients with covid-19. 7. declarations 7.1. acknowledgments we would like to express our gratitude to the administration and all personnel of afzalipour hospital and kerman university of medical sciences for their assistance and cooperation in this undertaking. 7.2. conflict of interest no potential conflict of interest relevant to this article was reported. 7.3. fundings and supports the study did not receive any funding from any organization. 7.4. authors’ contribution study concept 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the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references archives of academic emergency medicine. 2022; 10(1): e65 or i g i n a l re s e a rc h comparing emergency medical services processing times for stroke patients before and during covid-19 pandemic; a cross-sectional study thongpitak huabbangyang1, rossakorn klaiangthong1∗, krit prasittichok2, sutida koikhunthod3, jakkapan wanna3, nutthapong sudajun3, parichat khaisri3, anucha kamsom4 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. department of research and medical innovation, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. 3. faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. 4. division of biostatistic, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. received: june 2022; accepted: july 2022; published online: 16 august 2022 abstract: introduction: coronavirus disease 2019 (covid-19) has directly affected global healthcare, especially the frontline of healthcare provision, including emergency medical services (ems). the present study aimed to compare ems processing times and the number of acute stroke patients serviced by ems before and during covid-19 pandemic. methods: this is a retrospective observational review of bangkok surgico medical ambulance and rescue team (s.m.a.r.t.) ems data from 2018 to 2021. the ems processing times and the number of acute strokes were compared between pre-covid-19 era ( january 1st, 2018, and december 31st, 2019) and during covid-19 pandemic ( january 1st, 2020, and december 31st, 2021). results: the number of stroke patients transported by ems in one year, before and during covid-19 pandemic was 128 and 150 cases, respectively (change difference = 17.2%, 95% ci: 11.1–24.9). however, the average number of acute stroke patients per week was not significantly different (p = 0.386). the mean total ems processing times before and during covid-19 era were 25.59 ± 11.12 and 45.47 ± 14.61 minutes, respectively (mean difference of 19.88 (95% ci: 16.77–22.99) minutes; p < 0.001). the mean time from symptom onset to ems arrival (p < 0.001), the mean call time (p < 0.001), the mean response time (p < 0.001), and the mean scene time (p < 0.001) were significantly higher during covid-19 period. the mean transportation times for stroke patients was similar before and during covid-19 pandemic (10.14 ± 6.28 and 9.41 ± 6.31 minutes, respectively; p = 0.338). conclusion: during covid-19 pandemic, the number of acute stroke patients serviced by ems increased substantially, but there was no difference in the average number of patients per week. during the pandemic, ems processing times markedly increased. keywords: stroke; covid-19; emergency medical services cite this article as: huabbangyang t, klaiangthong r, prasittichok k, koikhunthod s, wanna j, sudajun n, khaisri p, kamsom a. comparing emergency medical services processing times for stroke patients before and during covid-19 pandemic; a cross-sectional study. arch acad emerg med. 2022; 10(1): e65. https://doi.org/10.22037/aaem.v10i1.1710. 1. introduction acute stroke is a severe neurological emergency that causes illness, mortality, and long-term morbidity. it is also an ∗corresponding author: rossakorn klaiaungthong; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok 10400, thailand. tel: +66 2244-3000, email: rossakorn@nmu.ac.th, orcid: https://orcid.org/0000-00025846-5754. important global public health issue (1). acute stroke is a time-sensitive condition. prompt evaluation and management are crucial to patient outcomes (2). as the first responders, emergency medical services (ems) play an important role in this. ems deliver patients to designated hospitals or stroke centers through a stroke fast track (3). several previous studies have confirmed that ems are important for rapid stroke center access, which increases treatment efficiency and positive outcomes in acute stroke patients (4, 5). covid-19 not only affected stroke patients, but also led to an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 2 increase in the incidence of other emergency medical conditions, such as acute coronary syndrome, and delayed treatment in the context of ems, reported in the previous systematic review and meta-analyses (6). since late 2019, the world faced coronavirus disease 2019 (covid-19). covid-19 began in hubei, china, and then spread dramatically around the world. thailand was one of the first countries outside of china to report infection. the first thai patient was confirmed on 13th january 2020 by thailand’s ministry of public health (7). subsequently, covid-19 continued to spread throughout thailand, affecting every sector. the pandemic directly affected the healthcare system, especially ems, as they are the first responders to emergency patients, including those with covid-19 (8). ems established improvements to their operations in response to covid-19, including protocol development and the use of personal protective equipment (ppe) to prevent infection of ems staff (9). the pandemic also affected ems processing times. in the usa, the number of patients requesting ems for conditions other than covid19 markedly decreased compared to that in the same period in the previous year, and the total number of ems requests decreased by 26.1% (10). yet, despite this, ems response times substantially increased during covid-19 (11). an observational study on the impact of covid-19 on acute stroke patients serviced by ems in busan, south korea, reported a decrease in the rate of acute stroke patients requesting ems by 8.2% and a doubling of ems processing times compared to that in the non-pandemic period (12). in massachusetts, usa, the number of ems callouts for acute stroke patients decreased by 12.3% during covid-19 pandemic (13). in catalonia, spain, the number of ems callouts for acute stroke patients decreased by 22.0% during covid-19 (14). however, data on changes in ems callouts for acute stroke during covid-19 has not yet been collated in thailand. the present study aimed to compare ems processing times and the number of acute stroke patients serviced by ems before and during covid-19 pandemic. 2. methods 2.1. study design and setting this is a retrospective observational review of bangkok surgico medical ambulance and rescue team (s.m.a.r.t.) ems data from 2018 to 2021. data on acute stroke patients serviced by ems in bangkok were collected from ems patient care reports and were used to compare ems processing times and the number of acute stroke patients serviced by the ems before and during covid-19 pandemic. the area studied was that covered by the surgico medical ambulance and rescue team, faculty of medicine, vajira hospital, navamindradhiraj university, bangkok. data were obtained from the s.m.a.r.t. of the faculty of medicine at vajira hospital, which is the primary ems unit in area one of bangkok’s nine areas. this team is dispatched by the erawan center in bangkok, which has six public and private hospitals in its network and is responsible for an area of 50 km2, with a population of 500,000 (15). the first covid-19 patient in the study area was confirmed on 13th january 2020 by thailand’s ministry of public health. during the study period, there were 437,303 confirmed covid-19 cases in the study area (16). during covid-19 pandemic, the s.m.a.r.t. introduced additional protocols for the screening of patients under investigation (pui) by paramedics or emergency nurse practitioners (enps) via the emergency medical hotline, 1554, or from the bangkok dispatch center. this required the emergency medical dispatcher (emd) to gather a patient symptom report and assess the risk of covid-19 infection. ems staff transporting patients were required to wear ppe and to avoid aerosol-generating procedures such as advanced airway management and mechanical cardiopulmonary resuscitation (cpr) in out-of-hospital cardiac arrest (ohca) patients. in the study area, at least three members of the s.m.a.r.t. staff attended each emergency. this could include emergency physicians (eps), paramedics, emergency nurse practitioners (enps), and emergency medical technicians (emts). 2.2. participants patient data were collected with the assistance of the s.m.a.r.t. of the faculty of medicine at vajira hospital, navamindradhiraj university. the data were obtained from ems patient care reports using the response code (rc) for acute stroke, which was “18 code red 1 red 9.” the period between january 1st, 2018, and december 31st, 2019, was defined as pre-covid-19 era, while the period between january 1st, 2020, and december 31st, 2021, was defined as during covid-19 pandemic. patients with a final diagnosis of acute stroke, rc code 18 with level red severity (18 red 1 red 9), aged > 18 years and assisted by the s.m.a.r.t. of the faculty of medicine, vajira hospital, navamindradhiraj university were included in our study. patients who refused treatment or transportation to hospital, those with incomplete data, and those treated with end-of-life or palliative care were excluded. 2.3. data gathering patient data were collected from ems patient care reports. these reports are recorded on a form that consists of ems operation unit data, patient data, and all treatments given by the ems team. the reports are recorded by the emd and the ems staff responsible for the patient. the primary purpose of the reports is the evaluation of ems service requirements when assigning healthcare funding for ems units. the forms filled out from 2018 to 2021 were retrospectively colthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e65 table 1: comparing the baseline characteristics of acute stroke patients as well as their ems processing times before and during the coronavirus disease 2019 (covid-19) pandemic characteristics covid-19 era p value before (n = 128) during (n = 150) number of patients per week mean ± sd 1.96 ± 1.15 2.17 ± 1.22 0.386 gender male 77 (60.2) 85 (56.7) 0.556 female 51 (39.8) 65 (43.3) age (year) mean ± sd 66.88 ± 14.33 66.11 ± 13.20 0.642 underlying disease yes 71 (55.5) 102 (68.0) 0.032 vital signs (prehospital) systolic blood pressure 157.22 ± 39.05 163.62 ± 35.15 0.152 diastolic blood pressure 92.68 ± 23.89 93.12 ± 23.15 0.876 heart rate 88.34 ± 21.87 93.14 ± 19.99 0.057 oxygen saturation 96.58 ± 3.03 97.05 ± 2.10 0.142 glasgow coma score 11.55 ± 3.40 12.51 ± 2.89 0.011 ems processing times (minutes) symptom to ems 13.52 ± 11.58 56.27 ± 76.6 < 0.001 call time 1.48 ± 0.77 3.62 ± 1.89 < 0.001 response time 2.75 ± 2.45 16.54 ± 8.86 < 0.001 scene time 12.23 ± 5.54 19.68 ± 7.81 < 0.001 transportation time 10.14 ± 6.28 9.41 ± 6.31 0.338 total 25.59 ± 11.12 45.47 ± 14.61 < 0.001 data are presented as number (%) and mean ± standard deviation (sd). ems: emergency medical services. figure 1: the average number per week of acute stroke patients, who were transported to hospital by emergency medical services (ems) before and during covid-19 period. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 4 figure 2: the average number per week of acute stroke patients, who were transported to hospital by emergency medical services (ems) before and during covid-19 period. lected, with the period from january 1st, 2018, to december 31st, 2019, defined as pre-covid-19; and the period from january 1st, 2020, to december 31st, 2021, defined as during covid-19. the data from ems patient care reports for all acute stroke patients meeting our criteria were recorded and saved in microsoft excel. this included patient demographic and clinical characteristics, including gender, age, underlying diseases, prehospital systolic blood pressure, prehospital diastolic blood pressure, prehospital heart rate, prehospital oxygen saturation, prehospital glasgow coma score, and time from symptom onset to ems arrival (in min); and ems processing time, including call time (in minutes), response time (in min), scene time (in min), transportation time (in minutes), and total processing time (in min). 2.4. definitions the period between january 1st, 2018, and december 31st, 2019, was defined as pre-covid-19, while the period between january 1st, 2020, and december 31st, 2021, was defined as during covid-19. ems processing time was the total time from the beginning of the call to emergency services to the arrival of the patient (by ambulance) at the designated hospital. call time was the time from the beginning of the emergency call to the order for ambulance dispatch. response time was the time from the end of the emergency call to ambulance arrival at the scene. scene time was the time from ambulance arrival at the scene to ambulance departure from the scene. transportation time was the time from ambulance departure from the scene to ambulance arrival at the designated hospital. the response code (rc) “rc 18 red 1 rc 18 red 9” was the code for acute ischemic or hemorrhagic stroke with a high severity level. 2.5. sample size determination for the primary objectives, mean values of each category were compared between before and during the pandemic (17). for the sample size calculation, we referred to statistical data from a previous study (18). the mean ems processing times for acute stroke patients before and during covid19 were 31.3 and 35.4 min, respectively, and the interquartile ranges (iqrs) were 23–37 and 25–41. the standard deviations (sds) were 10.37 and 11.85, respectively (12). the ratio of the sample size compared to the studied groups was defined as 1. we set the significance level as p > 0.05 and the power as 80%. the calculated minimum sample size was determined to be 116 per group. in the present study, the sample comprised acute stroke this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e65 patients serviced by the ems of the s.m.a.r.t., faculty of medicine vajira hospital, navamindradhiraj university, who matched our eligibility criteria over the 4 years. the number of patients during the pre-covid-19 period was 128, and the number during covid-19 was 150. thus, our total sample size was 278, which was sufficient for analysis. 2.6. statistical analysis to examine the distribution of variables, we converted the raw data to descriptive statistics. continuous variables were presented as the mean ± sd or the median and iqr. categorical variables were presented as frequencies and proportions. we compared the two groups using independent t-tests or mann–whitney u tests for numeric variables and chi-square or fisher’s exact tests for categorical variables. the differences between means before and during covid-19 were reported with 95% confidence intervals (cis). to compare the number of acute stroke patients serviced by ems before and during covid-19, data were described as frequency distributions and difference percentages between the two periods, with 95% ci. an interrupted time-series analysis with a linear first-order autoregressive model was used to compare the number of patients before and during covid-19 (change in the number of events per week to evaluate the change in the number of weekly ems stroke cases). statistical analyses were performed using spss statistics for windows, version 28.0. (ibm corp., armonk, ny, usa). a pvalue < 0.05 was considered statistically significant. 2.7. ethical statement this study was conducted in accordance with the tenets of the declaration of helsinki 1975 and its revisions in 2000. it was approved by the institutional review board of the faculty of medicine vajira hospital, navamindradhiraj university (coa no. 099/2565). the informed consent requirement was waived due to the retrospective nature and anonymity of all patient data. 3. results 3.1. baseline characteristics of studied patients table 1 compares the baseline characteristics of stroke patients before and during covid-19 pandemic. the number of stroke patients transported by ems in one year, before and during covid-19 pandemic was 128 and 150 cases, respectively (change difference = 17.2%, 95% ci: 11.1–24.9). however, the average number of acute stroke patients per week was not significantly different (1.96 ± 1.15 cases before and 2.17 ± 1.22 during covid-19; p = 0.386; figure 1). the mean age of patients before and during the pandemic were 66.11 ± 13.20 and 66.88 ± 14.33 years, respectively (p = 0.642). the proportions of male patients before and during covid-19 were 56.7% and 60.2%, respectively (p = 0.556). the mean systolic blood pressure (p = 0.152), diastolic blood pressure (p = 0.876), heart rate (p = 0.057), and oxygen saturation (p = 0.142) of stroke patients in prehospital setting was same before and during covid-19 era. the mean glasgow coma scale of patients was significantly higher during covid-19 pandemic (12.51 ± 2.89 vs. 11.55 ± 3.40; p = 0.011). in addition, the prevalence of underlying diseases during covid-19 era was higher than before the pandemic (68.0% vs. 55.5%; p = 0.032). 3.2. ems processing times figure 2 and table 1 compare the total ems processing times for acute stroke patients before and during covid-19 pandemic. the mean total ems processing times before and during covid-19 pandemic were 25.59 ± 11.12 and 45.47 ± 14.61 minutes, respectively (mean difference of 19.88 (95% ci: 16.77–22.99) minutes; p < 0.001). the mean duration from symptom onset to ems arrival (p < 0.001), the mean call time (p < 0.001), the mean response time (p < 0.001), and the mean scene time (p < 0.001) were significantly higher during covid-19 period (table 1 and figure 2). the mean transportation times for stroke patients was similar before and during covid-19 pandemic (10.14 ± 6.28 and 9.41 ± 6.31 minutes, respectively; p = 0.338). 4. discussion the number of acute stroke patients serviced by ems increased by 17.2% during covid-19 pandemic. the mean ems processing times, call times, response times, and scene times were all significantly higher during covid-19 pandemic compared to before, but there was no significant change in the transportation times. the present study supported the findings of previous systematic reviews and meta-analyses that have reported an increase in the incidence and risk of acute stroke in covid19 patients. several factors may increase the risk of acute stroke in covid-19 patients. these include abnormal coagulation, inflammation, platelet activation, and abnormal endothelial alterations (19, 20). velasco et al. found a 53.0% increase in ems callouts for acute stroke during covid-19 pandemic, most of which were in urban areas (21). it is likely that most ems callouts for all conditions, at all times, are in urban areas as they are more densely populated. however, this finding conflicted with those of several observational studies in other countries, including south korea (12), the usa (13), and spain (14), all of which found a decrease in incidence of acute stroke during covid-19. reasons postulated by the authors of these studies for this reduced incidence of stroke ems callouts are broad explanations for a general reduction in the number of patients accessing ems this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. huabbangyang et al. 6 during covid-19 era, including the declaration of a state of emergency, social restrictions (11), stay-at-home measures, social distancing measures, and self-isolation (10). in the present study, we found that the number of acute stroke patients serviced by ems in bangkok, thailand, increased by 17.2% during covid-19. this is likely to have been because people were more inclined to call out ems in medical emergencies rather than traveling to hospitals themselves or being taken by relatives, because the emergency departments of bangkok hospitals had to temporarily close during covid-19 pandemic to prevent co-mingling of covid-19 patients and medically vulnerable non-covid-19 patients. also, because of the frequent presentation of covid-19 patients in emergency departments, there was a need to ensure thorough disinfection of these departments and to quarantine high-risk staff. therefore, ems were often the sole means of access to hospital emergency departments. in addition, the declaration of a state of emergency by the thai government was accompanied by the implementation of a 22.00–04.00 curfew, effective between march 26th and june 30th, 2020. this provided an additional reason for people choosing ems rather than delivering patients to hospitals themselves, at least during the curfew hours. the increase in acute stroke patients seen by ems during covid-19 pandemic was also observed in a study by ikenberg et al., who reported an 86% increase in ems stroke rc during the lockdown (22). ems processing times, call times, response times, and scene times markedly increased during covid-19 pandemic. this result was compatible with those of previous studies that had found increased ems processing times during the pandemic (12, 14, 23, 24). the greatest increases in ems processing times in this study occurred during a period in which bangkok ems experienced a huge increase in callouts, both for covid-19 patients and other medical emergencies, with a greater frequency of calls to the emergency hotline 1669 than ever before, leading to many callers reaching a busy signal. moreover, the new covid-19 protocols required the emd at the bangkok dispatch center to gather pui medical histories and assess the covid-19 risk to attending ems staff. this increased call times and response times, despite the planning and implementation of strategies to stabilize operations during the pandemic. the primary strategy used to decrease call times was a computer-assisted triage system that separated and directed calls about covid-19 patients from those concerned with other medical emergencies. nonetheless, call and response times were still significantly increased during the pandemic in the present study. because of the risk of infection, the s.m.a.r.t. staff attending callouts were required to wear ppe to every emergency attended, leading to increased response times. the period during which staff were required to wear ppe was directly correlated with the increased response times (24). an additional protocol implemented during the pandemic was an en route call to the person who requested the service by the leader of the attending s.m.a.r.t. this was to evaluate the patient’s symptom severity and covid-19 risk, with questions about recent travel to high-risk areas for covid-19 infection and covid-19 symptoms such as an abnormal sense of taste or smell. this may have had additional effects on response times. during the pandemic, the attending ems staff faced difficulties in the evaluation and management of emergency patients, with contact precautions and ppe use interfering with communication and treatment. in the region studied, the ems team leaders are responsible for decisions about hospital delivery of acute stroke patients. however, before delivery, they must coordinate the reporting of patient symptoms and stroke fast track activation with emd at the bangkok dispatch center who, in turn, is required to pass on this information to the emergency department equipped for stroke patient management closest to the scene. during the pandemic, bangkok hospital emergency departments were overcrowded with both covid-19 and other emergency patients. as a result, some emergency departments were unable to admit new acute stroke patients, resulting in further increases in scene times. previous research indicated that this was also an issue in okayama during covid-19 pandemic, with delays in the delivery of emergency patients to hospitals due to overcrowded emergency departments with insufficient resources to deal with the increased number of patients (25). no difference was found between the mean ems transportation times before and during the pandemic. we posit that this is because, in the study location, most patients would not have been far from the designated hospital, and traffic conditions were not noticeably altered by the pandemic, with heavy congestion in the capital city, even during covid-19 pandemic. 4.1. strengths and limitations of this study a strength of the present study was its comparison of processing times and the number of acute stroke patients serviced by ems before and during covid-19. our results offer considerable potential benefits to ems in developing countries. the information on the effects of a medical crisis on ems treatment of time-sensitive diseases such as acute stroke can be utilized to improve the efficacy of ems and streamline their crisis response practices. there were several limitations in the present study. firstly, and most importantly, the only data obtained on acute stroke patients was prehospital information from the ambulance operation report. we did not have access to any information regarding their treatment in the emergency department or the administration of anticoagulants or other medications. secondly, due to the retrospective nature of our study, the data of some this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e65 acute stroke patients were incomplete, and these patients had to be excluded. thirdly, data were derived from only one medical facility (s.m.a.r.t., faculty of medicine, vajira hospital, navamindradhiraj university). hence, while our outcomes can be considered representative of effects on ems in equivalent or similar settings substantially affected by the covid-19 pandemic, they cannot be applied more broadly to other contexts. fourthly, the period between january 1st, 2018, and december 31st, 2019, was defined as pre-covid19, while the period between january 1st, 2020, and december 31st, 2021, was defined as the covid-19 pandemic period. this provided a study period of four years. however, strictly speaking, the covid-19 pandemic remained ongoing at the time this paper was written ( june 2022). lastly, the present study was observational. consequently, the effects of covid-19 on ems processing times and the number of acute stroke patients serviced by ems could not be comprehensively evaluated, and valid and reliable causality could not be inferred with certainty from the relationships between variables. future qualitative, prospective, and population-based studies are needed for the accurate attribution of causality. 5. conclusion during the 2 years of the covid-19 pandemic, the number of acute stroke patients serviced by ems substantially increased. however, there were no significant changes in the average number of acute stroke patients treated by ems per week. during the pandemic period, all ems processing times significantly increased. 6. declarations 6.1. acknowledgments we would like to thank the paramedics at the s.m.a.r.t. division of emergency medical services and disasters, faculty of medicine, vajira hospital, navamindradhiraj university, for facilitating data access and collection for the present study. our thanks also to dr. krit prasittichok and dr. rossakorn klaiaungthong for their research development suggestions. thanks to dr. chunlanee sangketchon, the chief of the department of disasters and emergency medical operations, faculty of science and health technology, navamindradhiraj university, for his support and research development suggestions. thanks to anucha kamsom of the division of biostatistics, faculty of medicine, vajira hospital, navamindradhiraj university, for her advice on statistical analyses. finally, our thanks to dr. aniwat berpan for his role in this study as an english language consultant. 6.2. authors’ contributions conceptualization: thongpitak huabbangyang, sutida koikhunthod, jakkapan wanna, nutthapong sudajun and parichat khaisri; methodology: thongpitak huabbangyang, rossakorn klaiaungthong and krit prasittichok; software: thongpitak huabbangyang and anucha kamsom; validation: thongpitak huabbangyang, rossakorn klaiaungthong and krit prasittichok; formal analysis: thongpitak huabbangyang and anucha kamsom; investigation: thongpitak huabbangyang, sutida koikhunthod, jakkapan wanna, nutthapong sudajun and parichat khaisri; resources: thongpitak huabbangyang, suthida koikhuntod, jakkapan wanna, nutthapong sudajun, parichat khaisri and rossakorn klaiaungthong; data curation: thongpitak huabbangyang and anucha kamsom; writing – original draft: thongpitak huabbangyang, rossakorn klaiaungthong and krit prasittichok; writing review & editing: thongpitak huabbangyang; visualization: thongpitak huabbangyang and rossakorn klaiaungthong; supervision: krit prasittichok; project administration: thongpitak huabbangyang; funding acquisition: rossakorn klaiaungthong 6.3. funding and supports the authors are grateful to the navamindradhiraj university research fund for pub. funding acquisition: rossakorn klaiaungthong. this research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors. 6.4. conflict of interest the authors have no conflicting interests to declare 6.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. references 1. prabhakaran s, ruff i, bernstein ra. acute stroke intervention: a systematic review. jama. 2015;313(14):145162. 2. zubair as, sheth kn. emergency care of patients with acute ischemic stroke. neurol clin. 2021;39(2):391-404. 3. ardebili me, naserbakht m, bernstein c, alazmaninoodeh f, hakimi h, ranjbar h. healthcare providers experience of working during the covid-19 pandemic: a qualitative study. am j infect control. 2021;49(5):547-54. 4. abdullah ar, smith ee, biddinger pd, kalenderian d, schwamm lh. advance hospital notification by ems in acute stroke is associated with shorter door-tocomputed tomography time andincreased likelihood of this open-access article distributed under the 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of patients with acute ischemic stroke during the covid-19 outbreak period: a multicenter study in daegu, korea. emerg med int. 2021;2021:6687765. 24. melaika k, sveikata l, wiśniewski a, jaxybayeva a, ekkert a, jatužis d, et al. changes in prehospital stroke care and stroke mimic patterns during the covid-19 lockdown. int j environ res public health. 2021;18(4):2150. 25. ageta k, naito h, yorifuji t, obara t, nojima t, yamada t, et al. delay in emergency medical service transportation responsiveness during the covid-19 pandemic in a minimally affected region. acta med okayama. 2020;74(6):513-20. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e80 http://dx.doi.org/10.22037/emergency.v5i1.18780 or i g i n a l re s e a rc h characteristics of methadone intoxicated children presenting to emergency department; a cross sectional study parvin kashani1, saeed safari2, hamidreza hatamabadi3, ali arhami dolatabadi3, mohammad manouchehrifar1, maryam dokht tabrizi3∗ 1. emergency department, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: september 2017; accepted: october 2017; published online: 13 october 2017 abstract: introduction: each year a large number of patients present to emergency departments (eds) following accidental or intentional poisoning with methadone. this study was designed with the aim of demographic evaluation of methadone poisoning in children presenting to ed and proposing preventive measures to parents and the healthcare system. methods: this cross sectional study was carried out on children under the age of 12 years presenting to ed of a poisoning referral center. demographic characteristics of the child and parents, cause of poisoning, form of drug consumed, dose consumed, the symptoms of the child on admission, clinical examination, laboratory findings, and final outcome were recorded and reported using descriptive statistics. results: 179 cases were studied (59.2% boys). cause of consumption was accidental in 175 (97.8%) cases and consumed drug dose was unknown in 53 (53.6%) cases. on admission 6 cases were in deep coma, 133 (74.3%) had miotic pupils, and 52 (29.1%) were affected with respiratory apnea and cyanosis. in 132 (73.8%) cases drugs were obtained from unapproved stores and form of drug consumed was syrup in 146 (81.6%) cases. 177 (98.9%) cases were discharged after 2 or3 days and 2 (1.1%) cases died. conclusion: based on the results of the present study, most cases of methadone poisoning were accidental, in children residing in poor and middle-class areas, with parents who had a low level of education and had obtained the drug from unapproved stores and stored it in improper containers or at improper places. only 64.8% of the parents were educated regarding drug storage. keywords: poisoning; pediatric emergency medicine; methadone; accident prevention; toxicity tests, acute © copyright (2017) shahid beheshti university of medical sciences cite this article as: kashani p, safari s, hatamabadi h, arhami dolatabadi a, manouchehrifar m, tabrizi m. characteristics of methadone intoxicated children presenting to emergency department; a cross sectional study. emergency. 2017; 5(1): e80. 1. introduction m ethadone is increasingly being used as a treatment for opium addiction and each year many individuals present to emergency departments (eds) following intentional or accidental poisoning with it (1, 2). clinical symptoms of methadone poisoning include loss of consciousness, respiratory depression, miotic pupils and other systemic (digestive, cardiac and neural) symptoms (3, 4). un∗corresponding author: maryam dokht tabrizi; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: +989122789330 e-mail: mdtabrizi1394@gmail.com fortunately, improper storage of the drug and children being able to access it has resulted in a considerable increase in presentation of children to ed following methadone poisoning (5-7). in a study in maryland, prevention of accidental poisoning in children was successful using resistant containers, yet this problem still remains (8). shadnia et al. showed that most accidental methadone poisonings had occurred due to consumption of the syrup form of drug and especially in children under 12 years of age (9). in iran, methadone is available as 5, 20, and 40 mg tablets and 5 mg/cc syrup. sadly, high prevalence of addiction to opium in iran and having methadone at home for treatment purposes, which makes it also accessible to the families of those being treated, have led to an increase in the number of pedithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 2 atric cases presenting with accidental poisoning. therefore, the present study was designed with the aim of demographic evaluation of methadone poisoning in children presenting to ed and proposing preventive measures to parents and the healthcare system. 2. methods 2.1. study design and setting this cross sectional study was carried out on children under the age of 12 presenting to poisoning emergency unit of loghmane hakim hospital, tehran, iran, from april 2015 for 18 months. this hospital is the referral center for poisoning cases in iran’s capital. the study was approved by the ethics committee of shahid beheshti university of medical sciences and the researchers adhered to ethical research practices based on declaration of helsinki and maintained confidentiality of patient data throughout the study period. while orally explaining the study protocol, informed consent was obtained from the patients’ parents for being included in the study. 2.2. participants all the children aged less than 12 years old with methadone poisoning who presented to the mentioned ed were evaluated. cases with suspicion to other poisonings, using multiple medications simultaneously, without a confirmed diagnosis, and having missing data were excluded from the study. 2.3. data gathering demographic characteristics of the child and parents (age and sex, educational level and occupation), cause of poisoning, form of drug consumed (tablet or syrup), dose consumed, history of addiction in parents, educations received in methadone maintenance therapy (mmt) clinics and their implementation by the parents were evaluated and gathered for all the patients via a pre-designed checklist. in addition, the symptoms of the child on admission, clinical examination findings, medical history, laboratory findings and final outcome (death, discharge) were also recorded for the patients. a senior emergency medicine resident was responsible for data gathering under the supervision of an emergency medicine specialist. the impression of methadone intoxication was made based on history taking and clinical examination and the diagnosis was confirmed by laboratory testing. 2.4. statistical analysis data were statistically analyzed using spss 21 software. to describe data, frequency and percentage or mean ± standard deviation were used. table 1: baseline characteristics of the studied children variable number (%) child’s sex boy 109 (60.9) girl 70 (39.1) the child’s guardian parents 161 (89.9) others 18 (10.1) area of residence poor 130 (72.6) middle-class 43 (24.0) wealthy 6 (3.4) parents’ university degree mother 40 (22.3) father 39 (21.8) parents’ occupation stay at home mother 127 (70.9) laborer father 133 (74.3) time of reaching the hospital less than 1 hour 16 (8.9) more than 1 hour 163 (91.1) 3. results 3.1. baseline characteristics 179 children with methadone poisoning diagnosis visited the mentioned ed during the study period (59.2% boys). table 1 shows the baseline characteristics of the patients. 71 (39.7%) cases were the only child in the family and 173 (96.6%) of the patients were residents of poor or middle-class areas of the city. cause of consumption was reported to be accidental in 175 (97.8%) cases and intentional in 4 (2.2%). consumed drug dose was stated as unknown in 53 (53.6%) cases. 3.2. clinical symptoms on admission only 71 (39.7%) patients were fully conscious and 6 (3.3%) cases were in deep coma. 133 (74.3%) cases had miotic pupils and 52 (29.1%) were affected with respiratory apnea and cyanosis. vomiting, itching, restlessness, ataxia, and drooping eyelid were detected in 29.5%, 13.9%, 1.67%, 1.11%, and 0.5% of the studied children, respectively. 3.3. obtaining and storing the drug in 132 (73.8%) cases drugs were obtained from unapproved stores and only in 47 (26.2%) cases from approved pharmacies. form of drug consumed was syrup in 146 (81.6%) cases and tablet in 33 (18.4%) cases. 116 (64.8%) of the parents had been educated on storing methadone by mmt clinics and 101 (87.1%) claimed that they had taken the necessary precautions regarding drug storage. place of storage was refrigerator in 67 (37.4%) cases and in other cases storage was done in other parts of the house accessible to children. drug was kept in a proper container in only 32 (17.9%) cases and in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e80 other cases it was stored in unlabeled containers along with other medications. 3.4. outcome 3 (1.67%) cases were discharged from the hospital after 2 days and 174 (97.2%) after 3 days of hospitalization in pediatrics department and naloxone prescription. 2 (1.1%) cases that were discharged against medical advice died. 6 (3.3%) of the cases encountered aspiration and 5 (2.8%) had seizure while, 4 (2.2%) needed cardiopulmonary resuscitation (cpr). metabolic acidosis, respiratory acidosis and respiratory alkalosis were seen in 12.8%, 25.1% and 2.2%, respectively. 4. discussion based on the results of the present study, most cases of methadone poisoning were accidental, in children residing in poor and middle-class areas, with parents who had a low level of education and had obtained the drug from unapproved stores and stored it in improper containers or at improper places. only 64.8% of the parents were educated regarding drug storage. most of the evaluated children (59.2%) in the present study were boys. in surveys by ghorbani et al. (10), sharif et al. (11) and esmaeili et al. (7), also boys were predominant with 59.3%, 56.9% and 58.3% frequencies, respectively. in a study by jabbehdari et al. (12), frequency of both sexes in methadone poisoning was the same. meanwhile, in a study by aghabiklooei et al. (13), girls were predominant (55.6%). in the present study, consumed drug dose was known in 65.4% of the cases. mean methadone dose consumed in aghabiklooei et al. study (13) was 130 mg, mean consumption was 33 mg for methadone syrup and 21mg for methadone tablets in jabbehdari et al. study (12), and 30 mg methadone syrup in sharif et al. study (11). based on avpu scale, more than half of the studied children (56.98%) were in a state of consciousness where they would respond when their parents talked to them in a loud voice and 39.66% were conscious. 3.35% of the evaluated children did not respond to any stimulation. the clinical symptoms observed in the studied patients were similar to other studies. in ghorbani et al. study (10) the most common symptoms of methadone poisoning in children included: sleepiness (61.9%), loss of consciousness (36.4%), vomiting (30.9%), miotic pupils (29.9%), cyanosis (22.7%), ataxia (14.4%), vertigo (8.2%), drowsiness (7.4%), apnea (6.2%), hypoxia (5.2%) and respiratory distress (4.1%). in the children studied by sharif et al. (11) the observed symptoms were: sleepiness (91.4%), miotic pupils (75.9%), vomiting (69%), apnea (53.4%), cyanosis (43.1%), seizure (8.6%) ataxia (6.9%) and hallucination (3.4%). additionally, in the study by jabbehdari et al. (12) the patients’ symptoms included: sleepiness (75%), miotic pupils (68%), vomiting (61%), and apnea (40%). the results obtained from the current study showed that 35.2% of the studied families had not received the necessary trainings from mmt clinics. on the other hand, only about half of all those who had been trained (56.4%) had implemented the teachings. considering the increasing prevalence of methadone poisoning in children, this statistic is very worrying and shows the poor performance of mmt clinics and related organizations. mmt clinics are responsible for educating all the individuals who get methadone from them and instruct them to implement the teachings and inform them on the irreversible consequences of disregarding the teachings and not implementing the necessary points. in addition, considering the role of media such as radio and television in increasing the awareness of the general population, short teasers should be made and broadcasted from radio and television. in our study, prevalence of methadone poisoning was higher in children who had parents with lower levels of education and resided in poor areas of the city. based on the findings of the present study, a large number of the evaluated families (73.2%) had obtained methadone from unapproved stores. therefore, regulatory authorities should continuously and accurately monitor these unapproved stores as well as mmt clinics and ask these centers to print safety instructions on drug brochures and avoid selling the drug without giving the necessary information to individuals. improper storage of this substance, especially in the form of syrup in soft drink bottles, which can be mistaken for water due to its color and appearance, increases the risk of poisoning in children. in this study, according to the parents’ statements, 97.8% of the children had consumed methadone accidentally and in most cases (69.3%), the container has not been specified for the drug. additionally, in 78.2% of the cases, the form of drug consumed was syrup. on the other hand, placing the tablet form of this drug in places within the reach of children (in out reports placing it on the kitchen counter, on the floor, on the table, etc.) increases the risk of the child eating it and being poisoned. among the other worrying statistics found in this study, it can be noted that in most of the methadone intoxicated children evaluated in this study (88.8%), more than 1 hour had passed from the presentation of symptoms when they reached the hospital. this can in turn lead to a raise in apnea and cyanosis cases and therefore, increase the risk of mortality. in this evaluation of 179 children, 2 were discharged against medical advice and died. this statistic shows that the parents and relatives are not aware of the irreversible consequences of this type of poisoning in children or they are not responsible enough. there is a need for giving enough information to the parents and the children, based on their age, and laws should be passed in this regard and a committee should monitor the execution of these laws. for obtaining more accurate and reliable results, it is suggested to reproduce the present study with a larger sample size in various this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. kashani et al. 4 cities all over iran and at different times to reach a more accurate pattern regarding these poisonings in children. then the corresponding authorities can design and implement an accurate and practical program in this regard by considering the needs of each area based on its findings. 5. conclusion based on the results of the present study, most cases of methadone poisoning were accidental, in children residing in poor and middle-class areas, with parents who had a low level of education and had obtained the drug from unapproved stores and stored it in improper containers or at improper places. only 64.8% of the parents were educated regarding drug storage. 6. appendix 6.1. acknowledgements this article was based on dr. maryam dokht tabrizi’s thesis for achieving her specialist degree in emergency medicine from shahid beheshti university of medical sciences. 6.2. author contribution all the authors meet the standard criteria of authorship based on the recommendations of international committee of medical journal editors. 6.3. funding/support no funds were received. 6.4. conflict of interest none. references 1. gibson jc, vulliamy a. accidental methadone poisoning in children: a call for canadian research action. child abuse & neglect. 2010;34(8):553-4. 2. alotaibi n, sammons h, choonara i. methadone toxicity in children. archives of disease in childhood. 2012;97(5):e1. 3. zamani n, sanaei-zadeh h, mostafazadeh b. hallmarks of opium poisoning in infants and toddlers. tropical doctor. 2010;40(4):220-2. 4. lovecchio f, pizon a, riley b, sami a, d’incognito c. onset of symptoms after methadone overdose. the american journal of emergency medicine. 2007;25(1):57-9. 5. fonseca f, marti-almor j, pastor a, cladellas m, farre m, de la torre r, et al. prevalence of long qtc interval in methadone maintenance patients. drug and alcohol dependence. 2009;99(1):327-32. 6. c martin t, rocque m. accidental and non-accidental ingestion of methadone and buprenorphine in childhood: a single center experience, 1999-2009. current drug safety. 2011;6(1):12-6. 7. esmaeili m, bayati z, gholitabar z-m. a report of childhood poisoning in babol. arch iranian med. 2004;7(4):297-9. 8. li l, levine b, smialek je. fatal methadone poisoning in children: maryland 1992–1996. substance use & misuse. 2000;35(9):1141-8. 9. shadnia s, rahimi m, hassanian-moghaddam h, soltaninejad k, noroozi a. methadone toxicity: comparing tablet and syrup formulations during a decade in an academic poison center of iran. clinical toxicology. 2013;51(8):777-82. 10. ghorbani f, salimkhani n, pakdel s. methadone poisoning in children and some factors affecting it: a crosssectional study in tabriz, northwest of iran. international journal of pediatrics. 2015;3(4.1):725-31. 11. sharif mr, nouri s. clinical signs and symptoms and laboratory findings of methadone poisoning in children. iranian journal of pediatrics. 2015;25(1). 12. jabbehdari s, farnaghi f, shariatmadari sf, jafari n, mehregan f-f, karimzadeh p. accidental children poisoning with methadone: an iranian pediatric sectional study. iranian journal of child neurology. 2013;7(4):32. 13. aghabiklooei a, hassanian-moghaddam h, zamani n, shadnia s, mashayekhian m, rahimi m, et al. effectiveness of naltrexone in the prevention of delayed respiratory arrest in opioid-naive methadone-intoxicated patients. biomed research international. 2013;2013. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e24 rev i ew art i c l e diagnostic accuracy of ultrasonography for detection of intussusception in children; a systematic review and meta-analysis erfan rahmani1, reza amani-beni2, yasaman hekmatnia3, amirhossein fakhre yaseri4, seyed amirabbas ahadiat5, parham talebi boroujeni6, moein kiani7, reza tavakoli2, seyyed-ghavam shafagh8, matin shirazinia9, setareh garousi9, mehran mottahedi9, mohammadreza arzaghi10, sasan pourbagher benam11, amir rigi12, amir salmani13, zeynab abdollahi14, fateme karimzade rokni15, tara nikbakht16, saeme azizi hassan abadi15, roozbeh roohinezhad8, forough masheghati17, yas haririan18, bahar darouei2, ehsan fayyazishishavan19, niusha manoochehri-arash20, mehrdad farrokhi21∗ 1. school of medicine, tehran university of medical sciences, tehran, iran. 2. school of medicine, isfahan university of medical sciences, isfahan, iran. 3. islamic azad university of medical science, sari, mazandaran, iran. 4. school of medicine, qazvin university of medical sciences, qazvin, lran. 5. the advocate center for clinical research, ayatollah yasrebi hospital, kashan, iran. 6. advanced diagnostic interventional radiology research center, tehran university of medical science, tehran, iran. 7. school of medicine, zanjan university of medical sciences, zanjan, iran. 8. faculty of medicine, iran university of medical sciences, tehran, iran. 9. faculty of medicine, mashhad university of medical sciences, mashhad, iran. 10.shahid beheshti university of medical sciences, tehran, iran. 11.faculty of medicine, urmia university of medical sciences, urmia, iran. 12.islamic azad university, zahedan branch, zahedan, iran. 13.mechanical engineering, sharif university of technology, tehran, iran. 14.department of radiology, school of medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran. 15.faculty of medical sciences, islamic azad university of chalus, chalus, mazandaran, iran. 16.islamic azad university, tehran medical branch, tehran, iran. 17.school of medicine, tabriz university of medical sciences, tabriz, iran. 18.school of medicine, shiraz university of medical sciences, shiraz, iran. 19.department of biostatistics and data science, school of public health, the university of texas health science center at houston (uthealth), houston, tx 77030, usa. 20.harvard medical school, boston, massachusetts, usa; division of endocrinology, diabetes, hypertension brigham and women’s hospital, boston, massachusetts, usa. 21.eris research institute, tehran, iran. received: december 2022; accepted: january 2023; published online: 28 february 2023 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 2 abstract: introduction: the diagnosis of intussusception can be challenging in children due to the fact that the findings of clinical evaluations are nonspecific and most of the patients present with unclear history. therefore, in this systematic review and meta-analysis, we aimed to investigate the diagnostic accuracy of ultrasonography for detection of intussusception and also compare the efficacy of point-of-care ultrasound (pocus) with radiologist-performed ultrasound (radus). methods: two independent reviewers systematically searched different online electronic databases including medline, scopus, web of science, google scholar, embase, and cochrane from inception to december 1, 2022 to identify published papers reporting accuracy of ultrasonography for diagnosis of intussusception. the quality assessment of the included studies was investigated using the quality assessment of diagnostic accuracy studies (quadas)-2 tool. results: a total of 1446 records were retrieved in the initial search of databases. after screening the titles, a total of 344 studies were retrieved for the detailed assessment of full-text. finally, 37 studies were included in qualitative and quantitative analysis. the pooled sensitivity and specificity of ultrasonography for diagnosis of intussusception were 0.96 (95% ci: 0.95-0.97) and 0.97 (95% ci: 0.97-0.98), respectively. the pooled positive likelihood ratio (plr) and negative likelihood ratio (nlr) were 24.57 (95% ci: 8.26-73.03) and 0.05 (95% ci: 0.04-0.08), respectively. the area under the hierarchical summary receiver operating characteristic (hsroc) curve was 0.989. mete-regression showed that there is no significant difference between diagnostic performance of pocus and radus (p = 0.06 and rdor (diagnostic odds ratio) = 4.38 (95% ci: 0.92-20.89)). conclusion: this meta-analysis shows that ultrasonography has excellent sensitivity, specificity, and accuracy for diagnosis of intussusception in pediatric patients. moreover, we found that diagnostic performance of pocus is similar to that of radus for diagnosis of intussusception. keywords: intussusception; ultrasonography; point-of-care testing; diagnostic imaging; meta-analysis cite this article as: rahmani e, amani-beni r, hekmatnia y, et al. diagnostic accuracy of ultrasonography for detection of intussusception in children; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e24. https://doi.org/10.22037/aaem.v11i1.1914. 1. introduction intussusception is the most prevalent cause of intestinal obstruction among the pediatric population younger than 6 years old, occurring in 1.1 to 4.3 children per 1,000 live births in europe and 0.5 to 2.3 children per 1,000 live births in united states with the male to female ratio between 1.4:1 to 4:1 (1). if this obstructive condition is left undiagnosed and untreated, it can potentially lead to fatal complications such as intestinal gangrene, necrosis, perforation, and death. indeed, prompt and appropriate diagnosis and management of intussusception in children is crucial to achieve a successful reduction using air enema (2). the diagnosis of intussusception can be challenging in children due to the fact that the findings of clinical and physical evaluations are nonspecific and most of the patients are younger than two years old, presenting with unclear history and symptoms such as abdominal discomfort and crying. previous studies have shown that the classic triad of colicky abdominal pain, vomiting, and “currant jelly” stool are found in less than 40% of cases on presentation to emergency departments, which means that more than 60% of cases are indistinguishable from acute gastroenteritis (3). abdominal ultrasonography is gradually emerging as the standard criterion for diagnosis in the emergency department due to its advantage of be∗corresponding author: mehrdad farrokhi; eris research institute, tehran, iran. email: dr.mehrdad.farrokhi@gmail.com, orcid: https://orcid.org/00000002-1559-2323. ing cost-effective, non-invasive, and radiation-free. although barium enema is known as the gold standard for diagnosis of intussusception, this modality requires an experienced radiologist, is expensive and invasive, and exposes cases to radiation, making it impractical in outpatient setting and emergency departments. there is a growing body of literature suggesting ultrasonography as a rapid, safe, and reliable imaging modality for diagnosis of intussusception in children (4-7). although multiple diagnostic studies have been recently published and ultrasound is suggested for the diagnosis of intussusception, their results were controversial with relatively wide confidence intervals. moreover, previous investigations have proposed that sonographers with limited experience or pediatric physicians as well as experienced radiologists can perform point-of-care ultrasound (pocus) (8-10). however, to the best of our knowledge, the comparison of diagnostic accuracy of pocus and radiologist-performed ultrasound (radus) for detection of intussusception has not been carried out in a systematic review and meta-analysis. therefore, in this systematic review and meta-analysis, we aimed to investigate the diagnostic accuracy of ultrasonography for detection of intussusception and also compare the efficacy of pocus with radus in this regard. 2. methods 2.1. literature search this systematic review and meta-analysis was carried out according to the guidelines of preferred reporting items for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e24 systematic reviews and meta-analysis of diagnostic test accuracy studies (prisma-dta). two independent reviewers (mf and rab) systematically searched different online electronic databases including medline, scopus, web of science, google scholar, embase, and cochrane from inception to december 1, 2022 to identify published papers reporting accuracy of ultrasonography for diagnosis of intussusception. the following keywords and medical subject heading (mesh) terms and also their combinations with boolean operators ‘’and” and ‘’or” were used for systematic search of the databases: “ultrasonography” or “ultrasound” or “sonography” or “ultrasonic” or “us” or “medical sonography” and “intestinal invagination” or “intussusception”. the references of the identified papers were also screened to retrieve the relevant articles more comprehensively. the disagreements between two reviewers were resolved via a consensus meeting or by a third reviewer. 2.2. eligibility criteria the eligible studies were included in our meta-analysis according to the following inclusion criteria: 1) diagnostic accuracy data including true positive (tp), false positive (fp), true negative (tn), and false negative (fn) can be extracted from a 2×2 table directly or data are available to calculate these items; 2) reported the diagnostic performance of ultrasonography for detection of intussusception; 3) the number of included cases was 10 or more; 4) the definite diagnosis came from the result of air or barium enema, surgical report, clinical follow-up, and finings of imaging by experienced radiologist or combination of them; 5) included cases <18 years old presenting with manifestations suggestive of intussusception. meta-analysis, reviews, comments, case reports, case series with less than ten patients, animal and cadaveric studies, studies with incomplete data regarding diagnostic characteristics of ultrasonography for diagnosis of intussusception were excluded. 2.3. data extraction the following variables were extracted from the included studies using the finalized data extraction excel sheet: first author, year of publication, country, study design, mean age, number of patients, prevalence of intussusception, tp, fp, tn, and fn. data extraction was carried out by two independent researchers and any discrepancies were resolved through a consultation with a third researcher. 2.4. quality assessment the quality assessment of the included studies was investigated using the quality assessment of diagnostic accuracy studies (quadas)-2 tool which evaluates the risk of bias and applicability of each study. similarly, the quality assessment was performed by two independent researchers and their disagreements were resolved by a third party. 2.5. data analysis statistical analysis was performed using meta-disc software version 1.4 (ramona cajal hospital, madrid, spain) and stata statistical software package (stata corp., college station, tx, usa) (version 17.0). the heterogeneity between the included studies was assessed using i2 and cochran-q test. if the value of i2 was higher than 50% or p-value of q-test was less than 0.10, dersimonian-laird random effect was used. alternatively, if the value of i2 was less than 50% and p-value of qtest was higher than 0.10, the data were pooled using mantelhaenzsel model. funnel plot, egger’s test, and begg’s test were used to investigate the publication bias. 3. results 3.1. search results a total of 1446 records were retrieved in the initial search of databases. seventeen studies were identified through manual search and citation tracking. after screening the titles, we removed 96 duplicated records and excluded 1023 articles based on the pre-defined criteria and a total of 344 studies were retrieved for the detailed assessment of full-text. finally, 37 studies were included in qualitative and quantitative analysis. the flow of the relevant studies is summarized in figure 1. 3.2. main characteristics thirty-seven studies with 6453 patients from 17 countries were included in this meta-analysis. these studies were published between 1986 and 2021. the mean age of the studied cases ranged from 6 to 72 months. the sensitivity and specificity of the studies ranged from 84.6 to 100 and 0 to 100, respectively. in this meta-analysis, we included 20 retrospective and 17 prospective cohort studies. ultrasonography by an experienced radiologist, clinical follow-up, surgical report, and air or barium enema were the most common gold standards reported in the included studies. true positive (tp), false positive (fp), true negative (tn), and false negative (fn) were also extracted from the studies. the main characteristics of the included studies are summarized in table 1. 3.3. quality assessment the quality assessment of the included studies was carried out using quadas-2 tool. the detailed results of this assessment are shown in table 2. taken together, the overall results of quality assessment suggest good quality. some items of quadas-2 were not well-described in conference abstracts, which led to high risk of bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 4 table 1: characteristics of the included studies authors year country study design age (months) number tp tn fp fn sensitivity specificity prevalence arnaud et al. (19) 1986 france retrospective 32 8 23 1 0 100 96 25% pracros j.p et al. (20) 1990 france prospective 426 145 281 0 0 100 100 34% bhisitkul et al. (21) 1992 usa prospective 17 65 20 42 3 0 100 93 31% verschelden et al. (22) 1992 usa prospective 18 83 34 43 6 0 100 88 41% woo et al. (23) 1992 south korea prospective 10 82 75 7 0 0 100 100 91% lim et al. (24) 1994 south korea prospective <18 y 176 64 112 0 0 100 100 36% shanbhogue et al. (25) 1994 netherlands retrospective 163 128 33 0 2 98.5 100 80% barzilai et al. (26) 1994 israel retrospective 14 5 8 1 0 100 89 36% wright et al. (27) 1996 australia retrospective 50 7 41 2 0 100 95 14% sarihan et al. (28) 1997 turkey prospective 38.8 27 21 4 0 2 91 100 85% stanely et al. (29) 1997 ireland prospective 11.4 25 7 16 2 0 100 89 29% john et al. (30) 1998 usa retrospective 18 151 48 101 1 1 99 98 32% harrington et al. (31) 1998 canada prospective 29.2 245 87 148 7 3 97 95 37% smoljanić et al. (32) 2000 serbia retrospective 21.4 35 26 9 0 0 100 100 74% henrikson et al. (33) 2003 usa prospective <18 y 19 11 7 1 0 100 88 58% eshed et al. (34) 2004 israel retrospective 13.8 151 37 104 7 3 93 94 26% justice et al. (35) 2007 vietnam prospective 9.3 585 466 106 1 12 97.5 99 82% hryhorczuk et al. (36) 2009 usa retrospective <10 y 812 97 698 15 2 97.9 97.8 12% muniz et al. (37) 2010 usa prospective 12.3 198 28 168 0 2 93.3 100 15% henderson et al. (38) 2011 usa retrospective 16 286 60 217 8 1 98.4 96.4 21% riera et al. (10) 2012 usa prospective 25 82 11 67 2 2 84.6 97.1 16% lin et al. (39) 2012 taiwan retrospective 72 775 15 760 0 0 100 100 2% zerzan et al. (40) 2012 usa prospective 99 8 88 2 1 88.9 97.8 9% jones et al. (41) 2012 uk retrospective 8 197 79 113 5 0 100 100 40% mwango et al. (42) 2012 kenya prospective 17 56 18 38 0 0 100 100 32% kim et al. (43) 2012 south korea retrospective 26 38 13 22 2 1 92.9 91.7 37% usang et al. (44) 2013 nigeria retrospective 6 25 20 1 1 3 87 50 92% chang et al. (8) 2013 taiwan retrospective 21 186 151 0 10 25 86 0 95% lam et al. (9) 2014 usa retrospective 31 46 10 34 2 0 100 94.1 22% lim et al. (45) 2015 usa retrospective 23 100 37 63 0 0 100 100 37% trigylidas et al. (13) 2017 usa retrospective 22 105 75 25 2 3 96 92.6 74% al-ani et al. (46) 2017 iraq retrospective 13 47 34 8 0 5 87 100 72% van houwelingen et al. (47) 2018 germany retrospective 29 10 8 1 0 1 89 100 90% lee et al. (7) 2020 south korea retrospective 25.5 575 70 483 22 0 100 95.6 13% arroyo et al. (4) 2021 usa prospective 24 100 8 89 1 2 88.9 97.8 8% bergmann et al. (5) 2021 multinational prospective 21.1 256 55 193 5 3 96.6 98 23% la tour et al. (6) 2021 canada prospective 18 131 39 83 3 6 86.7 96.5 34% tn: true negative; tp: true positive; fn: false negative; fp: false positive. 3.4. meta-analysis typical “shoulder arm shape” of sroc and spearman correlation coefficient between the log of sensitivity and the log of 1 specificity (0.353 with p = 0.03) showed statistically significant threshold effect. the evaluation of the heterogeneity of the diagnostic characteristics revealed a significant heterogeneity for sensitivity (i2=68.7% and p<0.01), specificity (i2=81.7% and p<0.01), positive likelihood ratio (plr) (i2=98.2% and p<0.01), negative likelihood ratio (nlr) (i2=54.7% and p<0.01), and diagnostic odds ratio (dor) (i2=61.6% and p<0.01). the pooled sensitivity and specificity of ultrasonography for diagnosis of intussusception were 0.96 (95% ci: 0.95-0.97) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e24 table 2: quality assessment of the included studies using quadas-2 tool study risk of bias applicability concerns patient selection index test reference standard flow and timing patient selection index test reference standard arnaud et al. ? ? pracros j.p ? ? ? bhisitkul et al. verschelden et al. woo et al. lim et al. § shanbhogue et al. barzilai et al. wright et al. § sarihan et al. ? ? ? ? stanely et al. ? john et al. ? § harrington et al. smoljanić et al. ? ? ? henrikson et al. ? eshed et al. § justice et al. hryhorczuk et al. § muniz et al. ? ? ? henderson et al. riera et al. lin et al. zerzan et al. ? ? ? ? jones et al. ? mwango et al. § kim et al. § usang et al. chang et al. § § lam et al. lim et al. § trigylidas et al. al-ani et al. § van houwelingen et al. lee et al. arroyo et al. § bergmann et al. § la tour et al. § § § : low risk; §: high risk; ?: unclear risk. and 0.97 (95% ci: 0.97-0.98), respectively (figure 2 and figure 3). the plr and nlr were 24.57 (95% ci: 8.26-73.03) and 0.05 (95% ci: 0.04-0.08), respectively (figure 4 and figure 5). the pooled dor for ultrasonography was 517.45 (95% ci: 260.471027.97; figure 6). the area under the hierarchical summary receiver operating characteristic (hsroc) curve was 0.989, suggesting that ultrasonography has an acceptable diagnostic performance (figure 7). meta-regression showed that there was no significant difference between diagnostic performance of pocus and radus for diagnosis of intussusception (p=0.06 and rdor=4.38 (95% ci: 0.92-20.89)). 3.5. publication bias evaluation of the studies using egger’s test (p=0.30) and begg’s test (p=0.50) showed no significant publication bias. furthermore, funnel plot of the included studies revealed no significant publication bias (figure 8). 4. discussion this systematic review and meta-analysis was carried out to investigate the diagnostic accuracy of ultrasonography for intussusception and also compare the efficacy of pocus with radus for diagnosis of intussusception. our analysis showed that the sensitivity and specificity of ultrasonography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 6 for diagnosis of intussusception are 0.96 and 0.97, respectively. the accuracy of ultrasonography was 0.98 according to hsroc. furthermore, meta-regression revealed that there was no significant difference between pocus and radus for diagnosis of intussusception. previous studies have shown that the use of pocus has a pivotal role in the management of life-threatening diseases by providing prompt diagnosis of the diseases (11, 12). in this regard, if not detected and managed early, intussusception can cause life threating complications such as intestinal gangrene, necrosis, perforation, and death. to reduce the risk of these complications, early diagnosis of intussusception in emergency departments would be crucial particularly in medical centers with no access to experienced pediatric radiologist (9, 10, 13). our findings showed that ultrasonography and particularly pocus can improve resource utilization by reducing time to diagnosis and prioritize the management of patients by providing early definitive treatment. therefore, our results are in line with increasing popularity of pocus for screening and diagnosis of pediatric emergencies (9, 10, 13). in a similar study, li et al. (14) investigated the performance accuracy of pocus and radus for diagnosis of intussusception. they included 14 studies with 2367 patients in their analysis. their study showed that the sensitivity and specificity of ultrasonography for diagnosis of intussusception are 0.94 and 0.96, respectively. the reported sensitivity and specificity of ultrasonography in their study were lower than ours (sensitivity: 0.96 and specificity: 0.97). however, similar to the results of our meta-regression, they found that there was no significant difference between radus and pocus for diagnosis of intussusception. the difference between the accuracy found in our study and this meta-analysis may in part be clarified by the fact that our study included more studies (37 vs. 14), particularly those published before 2000 and after 2017; therefore, our meta-analysis is more comprehensive and updated. similarly, in their meta-analysis, they found high heterogeneity among the included studies. one possible explanation for this high heterogeneity may be the fact that included studies had different sample sizes, gold standards for confirmation of the diagnosis, duration of followup of the patients, designs of the studies, and device types. traditionally, clinical evaluation and follow-up, x-ray, contrast enema, ct-scan, and magnetic resonance imaging (mri) are used for the diagnosis of pediatric intussusception. x-ray, computed tomography (ct)-scan, and contrast enema are not the first choice for the diagnosis of pediatric intussusception as they expose the patient to ionizing radiation and are expensive. contrast enema is known as the gold standard for detection and management of intussusception in pediatric patients, but it should be performed by an experienced pediatric radiologist (15-17). on the other hand, during the last years, ultrasonography has evolved to achieve more popularity as the first choice for the diagnosis of pediatric intussusception. although the use of ultrasonography for pediatric patients is accompanied with distinct advantages such as being safe, noninvasive, and inexpensive, providing realtime evaluation of the changes, and lacking ionizing radiation, this modality of imaging also has some critical limitations. ultrasonography cannot adequately detect pathological lead points and discriminate ileo-colic from ileo-ileal intussusception, which have a pivotal role in prompt and appropriate diagnosis and management of intussusception in children (18). the results of our meta-analysis support the increasing acceptance of ultrasonography for diagnosis of intussusception, but particular attention must be paid to some studies included in our analysis where ultrasonography showed weak diagnostic properties for identification of intussusception. in this regard, chang et al. (8) reported that ultrasonography for intussusception has sensitivity of 0.86 and specificity of 0, which differed considerably from other included studies. this inconsistency might be explained by the mixed use of sonographers with different levels of experience, lack of appropriate patient selection criteria, and the retrospective design of the study. ultrasonography is considered an operator-dependent modality of imaging in which lack of training and experience of sonographer can lead to misclassification bias and low diagnostic accuracy. our meta-analysis had some limitations such as heterogeneity in the design of the included studies, difference in experience level of sonographers, use of different gold standards for definite diagnosis of intussusception, and selection bias of the majority of included studies due to the retrospective design. since the included studies did not control possible confounders, the diagnostic performance of pocus cannot be easily generalized to all settings. furthermore, some studies did not report the experience level of sonographer who assessed the suspected patients. finally, it should be noted that we only included studies assessing suspected pediatric cases and our findings are not generalizable to other age groups. 5. conclusions this meta-analysis shows that ultrasonography has excellent sensitivity, specificity, and accuracy for diagnosis of intussusception in pediatric patients. moreover, we found that diagnostic performance of pocus is similar to that of radus for diagnosis of intussusception. however, further prospective studies with larger sample size are still required to establish these findings. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e24 6. declarations 6.1. acknowledgments the authors thank all 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assessment of pediatric ileocolic intussusception. pediatric radiology. 2009;39(10):1075-9. 37. muniz a. ultrasound diagnosis of intussusception by emergency physicians. acad emerg med. 2010;17(5):115. 38. henderson aa, anupindi sa, servaes s, markowitz ri, aronson pl, mcloughlin rj, et al. comparison of 2-view abdominal radiographs with ultrasound in children with suspected intussusception. pediatric emergency care. 2013;29(2):145-50. 39. lin w-c, lin c-h. re-appraising the role of sonography in pediatric acute abdominal pain. iranian journal of pediatrics. 2013;23(2):177. 40. zerzan j, arroyo a, dickman e, vazquez v. diagnosing intussusception by bedside ultrasonography in the pediatric emergency department. acad emerg med. 2012;19(suppl 1):s151. 41. jones t, das i, au-yong k, johnson k. an evaluation of the diagnostic accuracy of ultrasound in the diagnosis of paediatric intussusceptions. clinical radiology. 2012;67:s5. 42. mwango g, salim s, wambugu m, aywak a. role of abdominal 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jl, mccarville mb, davidoff am, et al. use of ultrasound in diagnosing postoperative small-bowel intussusception in pediatric surgical oncology patients: a single-center retrospective review. pediatric radiology. 2018;48(2):204-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e24 figure 1: preferred reporting items for systematic reviews and meta-analysis (prisma) flowchart of the literature search and selection of studies that reported accuracy of ultrasonography for diagnosis of intussusception. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 10 figure 2: forest plot of the pooled sensitivity of ultrasonography for diagnosis of intussusception. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e24 figure 3: forest plot of the pooled specificity of ultrasonography for diagnosis of intussusception. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 12 figure 4: forest plot of the pooled positive likelihood ratio (plr) of ultrasonography for diagnosis of intussusception. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e24 figure 5: forest plot of the pooled negative likelihood ratio (nlr) of ultrasonography for diagnosis of intussusception. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 14 figure 6: forest plot of the pooled diagnostic odds ratio (dor) of ultrasonography for diagnosis of intussusception. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e24 figure 7: hierarchical summary receiver-operating characteristic (hsroc) curve indicating accuracy of ultrasonography for diagnosis of intussusception. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 16 figure 8: funnel plot of publication bias on the pooled diagnostic odds ratio (dor) of ultrasonography. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusions declarations references archives of academic emergency medicine. 2021; 9(1): e56 rev i ew art i c l e facemask and respirator in reducing the spread of respiratory viruses; a systematic review negin shaterian1, fatemeh abdi2,3∗, zahra atarodi kashani4, negar shaterian5, mohammad darvishmotevalli6 1. student research committee, school of nursing & midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. school of nursing and midwifery, alborz university of medical sciences, karaj, iran. 3. non-communicable diseases research center, alborz university of medical sciences, karaj, iran. 4. department midwifery, iranshahr university of medical sciences, iranshahr, iran. 5. student research committee, jahrom university of medical sciences, jahrom, iran. 6. research center for health, safety and environment , alborz university of medical sciences, karaj, iran. received: may 2021; accepted: june 2021; published online: 16 august 2021 abstract: introduction:respiratory viruses spread fast, and some manners have been recommended for reducing the spread of these viruses, including the use of a facemask or respirator, maintaining hand hygiene, and perfoming social distancing. this systematic review aimed to assess the impact of facemasks and respirators on reducing the spread of respiratory viruses. methods: we conducted a systematic review using mesh terms, and reported findings according to prisma. pubmed, embase, cochrane library, scopus, proquest, web of science(wos), and google scholar were searched for articles published between 2009 and 2020. two independent reviewers determined whether the studies met inclusion criteria. the risk of bias of studies was assessed using newcastleottawa (nos) and consolidated standards of reporting trials (consort). results: a total of 1505 articles were initially retrieved and 10 were finally included in our analysis (sample size: 3065). 96.8% of non-infected participants used facemask or respirator in contact with people infected with a respiratory virus, facemask and respirator have a significant effect on reducing the spread of respiratory viruses. conclusion: evidence support that using a facemask or respirator can reduce the spread of all types of respiratory viruses; therefore, this result can be generalized to the present pandemic of a respiratory virus (sars-cov-2) and it is recommended to use a facemask or respirator for reducing the spread of this respiratory virus. keywords: masks; respiratory protective devices; respiratory tract infections; virus diseases; n95 respirators cite this article as: shaterian n, abdi f, atarodi kashani z, shaterian n, darvishmotevalli m. facemask and respirator in reducing the spread of respiratory viruses; a systematic review. arch acad emerg med. 2021; 9(1): e56. https://doi.org/10.22037/aaem.v9i1.1286. 1. introduction in recent decades, humans have been threatened by a variety of viruses that lead to acute respiratory infections affecting human life and human societies, sometimes leading to death. there are several routes of respiratory virus transmission: contact, droplet, and aerosol. respiratory viral infections cause a wide range of overlapping symptoms, known as acute respiratory illness (ari) or, usually (more commonly) ∗corresponding author: fatemeh abdi; alborz university of medical sciences, taleghani boulevard, taleghani square, karaj, iran. email: abdi@sbmu.ac.ir, tel:+9826 34197000, orcid: https://orcid.org/0000-00018338-166x. “the common cold” as a whole, which is chiefly mild but may cause severe illness and death (1). to protect themselves against such viruses, humans have offered a variety of strategies, from wearing facemasks and home quarantine to producing drugs and making the body resistant to such particles using appropriate vaccines. when specific vaccines or disinfection treatments are not available, the use of non-drug interventions, such as wearing respiratory personal protective equipment (rppe), is important for protecting and reducing the occupational risk of health care workers (hcws) against respiratory infections (2). common types of ppe include surgical masks and respirators. it should be noted that surgical masks are loose and disposable and create a physical barrier between the wearthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 2 ers’ mouth and nose and environmental contaminants (large respiratory droplets or sprays of blood and body fluids). they are not designed to filter out small airborne particles and have very different level of protection (3, 4). in this regard, the results of some studies have shown that daily use of surgical masks in all areas of the hospital is important in reducing swine flu infection, such measures at least prevent touching the mucous membranes of the nose and mouth with the fingers and such unconscious behaviors are less common (5, 6). these masks should be replaced as soon as they get wet or at least every four hours (3). in contrast, n95 respirators or their european equivalent, ffp2-3 prevent the penetration of at least 95% of aerosols less than 5 mm. but due to resistance to respiration and heat their long-term use is intolerable for hcws (4). they should be worn for less than 8 hours during the day and should not be reused if they get wet (3). besides, the equipment needs to fit completely on the face. it is very difficult to use this equipment in people with facial hair or beard and children, and is not recommended for the elderly, claustrophobic, and people with lung disease. powered air-purifying respirators (paprs) have blowers that provide positive pressure airflow through the filter. they do not need to fully fit, and they protect the head and neck contiguously. one of its disadvantages is being the most expensive ppe. the world is currently suffering from a pandemic (7), caused by a virus now known as severe acute respiratory syndrome coronavirus 2 (sars-cov-2) (named by the international committee on taxonomy of viruses (ictv )), which has a phylogenetic similarity to sars-cov and its resulting disease is called covid-19 (8, 9). recommendations for the use of surgical masks during the present coronavirus disease pandemic include: people with suspected or confirmed respiratory infection covid-19 symptoms; people in contact with hcws or first-aid workers, and hcws in contact with people with symptoms of respiratory infection (3). the present study aims to assess the effect of wearing a facemask on the reduction of incidence and prevention of infection with respiratory viruses such as sars-cov-2. 2. methods this systematic review is reported based on the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines (10). 2.1. search strategy in this systematic review, google scholar, pubmed, embase, cochrane library, scopus, proquest, and web of science (wos) were searched for articles published between 2009 and 2020. boolean operators such as "and" and "or" were used to make different combinations for search (11). in addition, we searched using the following terms: 1–"facemask" [mesh] or "facemasks" [mesh] or "mask" [mesh] or “n95 respirator” [mesh] or “respirator, n95” [mesh] or “n95 face masks” [mesh] or “face mask, n95” [mesh] or “mask, n95 face” [mesh] or “n95 face mask” [mesh] or “n95 masks” [mesh] or “mask, n95” [mesh] or “n95 mask” [mesh] or “n95 filtering facepiece respirators” [mesh] or “n95 ffrs” [mesh] or “n95 ffr” [mesh] 2-"respirators"[mesh] or"device, respiratory protective" [mesh] or "protective device, respiratory" [mesh] or "respirators, industrial"[mesh] or "respirators, airpurifying"[mesh] 3-"respiratory virus"[mesh] or " severe acute respiratory syndrome virus" [mesh] or "sars-related coronavirus" [mesh] or "sars-cov"[mesh] "sars coronavirus"[mesh] or "sars-associated coronavirus"[mesh] or "coronavirus, sars-associated"[mesh] or "sars associated coronavirus"[mesh] 4-#1 and #2 and #3 2.2. type of studies all studies published between 2009 and 2020, which were conducted to assess the effect of facemask on preventing the of spread respiratory viruses and reported the number or percentage of participants using a facemask and getting or not getting infected with a respiratory virus, were included in the study. publications such as reviews, letters, comments, and case reports and studies that were conducted just for comparing different types of facemasks, or evaluated people with a tissue graft, or their sample size was not clear were excluded from the study. there were no language restrictions for using and entering articles in this study. if the language used in an article was not persian or english, we asked a translator to translate the article. 2.3. types of participants the studies were selected if their participants were: -people in contact with those infected with respiratory viruses people who were members of specific groups such as healthcare personnel, emergency department and general ward staff, public health workers, hajj pilgrims 2.4. types of interventions the studies were reviewed if: participants used ppe -measured the effect of facemask or ppe on preventing transmission of respiratory viruses 2.5. type of outcome measure all studies measured the number and percentage of participants who used facemask, ppe, vaccine, and distance or did not use them and were infected after being in contact with a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e56 person infected with respiratory viruses. 2.6. study selection the title and abstract of all studies retrieved during the electronic and manual follow-up search process were assessed based on the inclusion criteria. the full texts of relevant papers were examined based on the mentioned criteria. 2.7. quality assessment in this study, the quality of cohort and cross-sectional studies was assessed according to the newcastle-ottawa scale (nos) (12); and the quality of controlled-trial studies was assessed based on consort. a maximum of ten stars was given to each study based on the nos. a maximum of five stars was given to selection (including sample size, nonrespondents, and ascertainment of the exposure). a maximum of two stars was given to comparability (including the study control for the most important factor). a maximum of three stars was given to outcome (including assessment of the outcome and statistical test). studies of high-quality score nine or ten stars, studies with a score of seven or eight stars were considered to be of medium quality, and studies scoring less than six stars were considered to be of low quality (13). the consort checklist was also used to report the standard clinical trial studies. this checklist contains 24 questions and a score of 0 or 1 is given to every question. if a study scored above 15, it was included in the study and thoe scoring 15 and below were excluded (14). the quality score for each article is shown in table 1. 2.8. data extraction two investigators independently searched for relevant scientific publications, carried out validity assessments, and resolved any disagreements by consulting a third investigator (15). data were collected as follows: 1. research information (reference, type of study, location, and sample size (male, female)) 2. characteristics of the participants (population, and age) 3. intervention and comparison of the details (type of viruses, type of contact with an infected person, ppe type, facemask type) 4. outcome measures (number of ppe types, number of facemask types, infected participants using facemask, distance, time of contact with person, time of using facemask, and vaccinated people) 2.9. statistical analysis we calculated the number and percentage of infected and non-infected people in all included studies and reported them in tables. 3. results the systematic search in the databases identified 1505 articles. after reviewing their titles and abstracts, 753 duplicate articles, 654 records with undesirable study types, and 88 irrelevant articles were removed. finally, 10 articles (sample size=3065) were included in the systematic review. the flowchart of studies included in this review is shown in figure 1. the characteristics of included studies are presented in table 1 and their main findings are shown in other tables. the most frequent places where the studies were conducted were california (16, 17), korea (18, 19), saudi arabia (20, 21), thailand (22), germany (23), australia (24), sydney (25), and new south wales (25), respectively. 3.1. factors examined in the studies the factors presented in table one include the author’s name, study design, type of population, sample size, age, result, and quality score. table two includes type of virus, type of contact with an infected person, ppe type, facemask type, and infected participants who used masks after contact with the patient. 3.2. type of virus, contact, ppe, facemask, and the number of infected people who used a facemask type of virus the types of virus assessed in this systematic review included sars-cov-2 (16), mers (18), mers-cov (19, 20, 22), rhinovirus (21, 24, 25), influenza a viruses (h1n1) (17, 21, 2325), influenza b viruses (21, 23-25), parainfluenza 1,2 and 3 viruses (21, 24), enteroviruses (21), adenoviruses (24, 25), human metapneumoviruses (24, 25), respiratory syncytial viruses a or b (25), coronaviruses (24, 25), picornaviruses (25), and enteroviruses (25). 3.3. type of contact the type of contact with an infected person was assessed in nine articles and varied in different studies. generally, the contact was between health care workers and infected persons (16, 17, 20, 22, 24), emergency department and general ward (18), public health workers (19), hajj pilgrims (21), and household contact (23, 25), contact with aerosol, and skinto-skin contact. 3.4. ppe type the ppe type was mentioned in all assessed studies. ppe types in the studies included gloves (16-20, 22), kind/various types of facemask (16-25), n95 respirator (17, 18, 20), gown (17, 20, 22), face shield, eye protection (20, 22), and cap (22). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 4 3.5. type of facemask the type of facemask was mentioned in nine studies and the number of participants who wore each type of facemask was mentioned in seven studies. surgical masks (18, 19, 21, 23, 25) were used by 18.8%, n95 respirators (17-20, 22, 24) by 34%, medical masks (20) by 16.1%, and p2 masks (25) by 3% of participants. 3.6. the number of infected people who used a facemask or n95 respirator generally, 3.2% of participants who wore a facemask became infected with the respiratory virus through contact with an infected person. in studies that all participants wore surgical masks (18, 19, 21, 23, 25), 0.3% of them became infected. in studies that all participants wore n95 respirators (17-20, 22, 24), 1.4% became infected. 0.2% of participants who wore n95 respirators and surgical masks became infected (18, 19). 1.7% of participants who wore n95 respirators and medical masks became infected (20). 0.3% of participants who wore n95 respirators and other facemasks became infected (17) and 0.5% of participants who wore p2 masks and surgical masks became infected (25). also, some studies did not mention the effect of each facemask on preventing virus spread and the percentage of using each type of facemask so it was not possible to draw a precise conclusion about the quality and effectiveness of each type of facemask based on the mentioned statistics. 3.7. distance and time of contact distance between people and the duration of contact with an infected person was mentioned in five studies (16, 19-22). we could not assess the effect of distance and duration of contact on preventing the spread of virus because these studies did not mention the count of the infected participants based on distance and duration of contact. 3.8. duration of using a facemask and vaccinated the duration of facemask use and the number of vaccinated people were evaluated in five studies (17, 20, 23-25). however, these studies did not mention the effect of vaccination and duration of facemask use on prevention of virus infection. 4. discussion the results of the present study showed that using facemask or respirators has a preventive effect on the spread of respiratory viruses including sars-cov-2, mers-cov, rhinovirus, influenza a virus (h1n1), influenza b viruses, parainfluenza 1,2 and 3 viruses, enteroviruses, adenoviruses, human metapneumoviruses, respiratory syncytial viruses a/b, coronaviruses, picornaviruses, and enteroviruses. moreover, the percentage of transmission of respiratory viruses in people who wore any type of facemask or n95, respectively, was 0.3% in the surgical mask group, 1.4% in the n95 respirators group, 0.2% in n95 respirators and surgical mask group, 1.7% in n95 respirators and medical mask group, 0.3% in n95 respirators and another facemask group, and 0.5% in p2 masks and surgical mask group. in covid-19 disease pandemic, due to the lack of access to appropriate antiviral medications and the lack of a suitable vaccine, infection control was the most important way to control it (26). therefore, many countries performed non-drug interventions and early control strategies that included the use of facemasks and double key actions such as hand hygiene and temporary closure of schools and offices as recommended by the international scientific communities (25). sars-cov-2 transfer is mainly through direct transfer of droplets by sneezing and coughing and contact; also, airborne transfer is possible via aerosol-generating procedures (agps) (24, 27, 28). moreover, it has been shown that large droplets could accelerate the transfer of fomite and suspended in the air (28). besides, these large droplets can move up to two meters or eight meters (28). in this regard, liu et al. showed that a high concentration of virus is in the air sample of the patient’s toilet and in the environment in which hcws their ppe (29). hence, virus-infected particles are more likely to be suspended in the air in places where the airflow is turbulent and patients with or without symptoms or in the pre-symptom phase of covid-19 have many referrals (30). and health care workers are more likely to become infected (46). in this regard, the rate of influenza virus transmission between hcws in the h1n1 pandemic were 14%, yet 67% of them did not have any signs (31). besides, most positive cases were between outpatient and ancillary hcws and hcws who used surgical masks or n95 respirators were seronegative (31). this indicates that they’d not use ppe such as facemasks (31). moreover, ki et al. showed that emergency department staff had more exposure to respiratory infections mers disease compared to the internal department staff (in terms of time, the medical staff of the emergency department spent more time with the index patient than those working in the internal department, eight hours versus one hour). however, the rate of being stricken with disease was 3% vs 16.7%, respectively, because 93% of emergency department staff used surgical masks and 95% of them used hand wash but only 8% of the general department staff used surgical masks (32). it should be noted that in studies, the proportion of infected hcws among the confirmed cases of coronavirus disease2019 is 10% in italy, 20% in spain, and 40% in the united states (33). infected hcws can be a source of infection for other hcws and patients (4). therefore, the protection of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e56 hcws and the provision of ppe are of particular importance to maintaining ongoing care and the function of the health care system. on another hand, liu et al. showed that the rate of rna virus was reduced by performing a disinfection procedure in the ppe room (29). this emphasizes the effect of environmental disinfection in reduction of virus transmission (29). therefore, in addition to providing ppe for hcws, health organizations should emphasize continuous training on donning and doffing for effective protection (34, 35). study results showed that the infection control team of the hospital can significantly reduce the transmission of the disease between hcws through early diagnosis and identifying index cases among patients and explaining preventive actions to them, giving early leave to sick staff, or at least giving them some recommendations such as maintaining social distance with other staff, hand hygiene observation, and wearing facemask during a disease outbreak, and monitoring the adherence to infection control methods (26). in addition to hcws’ awareness, climate condition is another factor that obstructs the correct use of respiratory protection equipment between hcws (36). studies state that in a household setting, due to the increased cumulative exposure time of index patients with family members, the possibility of transmitting viral respiratory infections is higher (37, 38). in this regard, results of studies showed that if family members perform non-drug interventions (such as wearing facemask and maintaining hand hygiene for the prevention of home flu), during 36 hours after onset of symptoms in the index case, the incidence of influenza will be significantly lower in family members compared to control group. one of the possible reasons is that the virus shedding often occurs during the first 36 hours so if the preventive interventions start sooner, the probability of home transmission of disease will be lower. moreover, this study showed that the permanent use of facemask is tolerable and acceptable for both adults and children. in this regard, another study on the effect of non-drug interventions (wearing facemask and hand hygiene) in home environments in bangkok, thailand failed to see any effect. of course, it should be mentioned that index patients who were infected with influenza (children) slept with their parents without wearing facemask throughout the night, which may block any effect of interventional protection during the day (39). in a random retrospective cluster clinical trial study, macintyre et al. revealed that less than 50% of participants had the necessary compliance for wearing a facemask and in this group had a significantly lower risk of influenza-like illness due to infection (25). results of another study in a social setting such as a student dormitory showed that influenza-like illness was significantly less in the group that used a facemask, and the group that both used a facemask and maintained hand hygiene compared to the control group. they suggested that adding hand disinfectant does not increase the protective efficacy of wearing a facemask or at least does not increase it significantly (40). results of these studies show that if index patients and people around them do non-drug interventions such as wearing a facemask and washing their hands in domestic or social settings during the first 36 hours, these can significantly reduce the incidence of respiratory infection in people around them. one of the important religious rituals is hajj, in which large numbers of people from different countries congregate in a particular region. thus, it naturally increases the risk of transmitting respiratory viral infections. results of studies show that use of facemasks by people with the influenza-like illness and those around them (those who were in a tent together) provided more protection against the influenza-like illness compared to those in the control group, who did not wear protective equipment, and the percentage of infection in each group was 31% vs. 53%, respectively. a significant point in this report was the presence of a positive correlation between duration of facemask use and protection against influenza-like illness, so the incidence of disease in pilgrims who wore facemask more than eight hours a day compared to those who wore a mask for less than eight hours a day was 3% vs 43% (21). currently, due to the intensity of the covid-19 pandemic, wearing a facemask is common everywhere, including hospitals and communities (3). in this regard, the results of studies indicate that wearing a facemask is more effective in controlling the spread of infection, especially from asymptomatic carriers. the inward efficacy surpasses outward efficacy and the public’s use of facemasks plays a greater role in controlling the source of infection. of course, wearing a facemask is recommended as a method of infection control and primary prevention for healthy persons (26, 41). lai et al showed that the use of facemask by hcws is logical and the use of facemasks, even low-quality cloth masks, by the public should be implemented in the community, immediately. if people can use medical masks, without medical staff running out of ppe reserves, it will be more effective in the prevention of disease transmission. the use of cloth masks by patients or infectious individuals without clinical symptoms prevents infection transmission in the community. of course, the filtration effects of cloth masks are generally lower than surgical masks. however, if they are well designed (multi-layered cloth masks made of water-resistant fibers with high yarn density and delicate cloth) and used properly (so that the whole face fits in it) they may provide reasonable protection. it has also been shown that these masks can decrease virus exposure, although their ability is much less than medical masks. therefore, hcws should not use this type of mask, since the rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 6 sults of studies show that the risk of infection among hcws who use cloth masks is higher than those who use the medical mask or control group (42). thus, cdc expressed that at the time of covid-19 pandemic and due to the limited resources of medical masks, the public could use hand-made cloth masks to optimize facemask stocks. also, they should be advised to wash their hands daily with hot water and soap, and other appropriate methods. besides, the public should be educated about their use (27). therefore, ppe should be selected for special settings and they should be used logically (4). it was thought that n95 respirators have more efficacy in filtering very small particles than surgical masks. however, the results of studies show that in non-infectious health care settings, surgical masks do not have lower protective efficacy than n95 respirators in hcws (43-46). however, results of one cluster clinical trial showed that the rate of respiratory infections in hcws who always use medical mask was double compared to hcws who always used n95 respirators, and the highest rate of infection was among hcws who had close contact with patients such as radiologists, followed by nurses. nevertheless, that study did not have enough power for the results to be generalized, since the rate of observed infection was much lower than expected (24). 5. limitations the limitations of this study included lack of access to fulltext of some studies, lack of data on the effect of facemasks on prevention of each type of respiratory viruses in articles that had studied different viruses, the lack of data on the effect of each type of facemask on reducing the transmission of respiratory viruses and count or percentage of participants who used a facemask. moreover, some studies conducted on recent viruses (sars-cov-2) were not published in english, which is another limitation of the study. 6. conclusion this systematic review showed that using facemasks or respirators aided in preventing the spread of respiratory viruses. the result of the present systematic review showed that using facemasks could prevent the spread of virus. we recommend conducting more studies on the effect of each type of facemask and respirator, individually, and on the prevention of the spread of different viruses. moreover, we suggest assessing the effect of simultaneous use of masks, duration of using a facemask, and distance between healthy people and the person infected with respiratory viruses. 7. declarations 7.1. acknowledgments the authors acknowledge alborz university of medical sciences. 7.2. funding and support this study did not receive any funding support. 7.3. author contribution fa and nsh fulfilled an advisory role. za carried out the literature survey. nsh edited this manuscript in english. md commented on the manuscript. all authors passed the criteria for authorship contribution 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suntarattiwong p, levy j, jarman rg, kaewchana s, gibbons rv, et al. findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in bangkok, thailand. influenza and other respiratory viruses. 2011;5(4):256-67. 40. aiello ae, murray gf, perez v, coulborn rm, davis bm, uddin m, et al. mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial. the journal of infectious diseases. 2010;201(4):491-8. 41. eikenberry se, mancuso m, iboi e, phan t, eikenberry k, kuang y, et al. to mask or not to mask: modeling the potential for face mask use by the general public to curtail the covid-19 pandemic. infectious disease modelling. 2020. 42. macintyre cr, seale h, dung tc, hien nt, nga pt, chughtai aa, et al. a cluster randomised trial of cloth masks compared with medical masks in healthcare workers. bmj open. 2015;5(4):e006577. 43. malik t. covid-19 and the efficacy of different types of respiratory protective equipment used by health care providers in a health care setting. cureus. 2020;12(4). 44. boškoski i, gallo c, wallace mb, costamagna g. covid-19 pandemic and personal protective equipment shortage: protective efficacy comparing masks and scientific methods for respirator reuse. gastrointestinal endoscopy. 2020. 45. radonovich lj, simberkoff ms, bessesen mt, brown ac, cummings da, gaydos ca, et al. n95 respirators vs medical masks for preventing influenza among health care personnel: a randomized clinical trial. jama. 2019;322(9):824-33. 46. smith jd, macdougall cc, johnstone j, copes ra, schwartz b, garber ge. effectiveness of n95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis. cmaj. 2016;188(8):567-74. 47. wiboonchutikul s, manosuthi w, likanonsakul s, sangsajja c, kongsanan p, nitiyanontakij r, et al. lack of transmission among healthcare workers in contact with a case of middle east respiratory syndrome coronavirus infection in thailand. antimicrobial resistance & infection control. 2016;5(1):21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e56 figure 1: flowchart of the review. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 10 table 1: overview of all the studies included in this systematic review reference study design location population sample size (n, %) age (year) result quality score amy heinzerling (2020)(16) cohort california healthcare personnel t:43 m: 16% f: 84% 27 – 60 reducing the risk of sars-cov-2 transmission using patient source control (e.g., a patient wearing a facemask or connected to a closed-system ventilator during hcp exposures) 7* hyun kyun ki (2019)(32) case–cohort korea emergency department and general ward t: 446 m: 46.9% f: 53.1% 20 78 great reduction in nosocomial transmission of mers by routine infectionprevention policies such as wearing a surgical mask and hand hygiene 9* boyeong ryu (2018)(19) crosssectional korea public health workers t: 34 m: 58.8% f: 41.1% 34 – 56.7 properly use of ppe lead to a lack of evidence of mers on public health provider basem m. alraddadi 7* (2016)(20) cohort saudi arabia healthcare personnel t: 250 m: 64.4% f: 35.6% 18 66 more protective against mers cov infection while in close contact with an infected patient by n95 respirators highlight the possible role of shortrange aerosol transmission of merscov in healthcare settings 7* surasak wiboonchutikul (2016)(47) crosssectional thailand healthcare workers t:38 m: 21.1% f: 78.9% 38.6 healthcare workerscan be protected via strict infection control precaution 7* osamah barasheed (2014)(21) controlled trial saudi arabia australian hajj pilgrims t: 164 m: 43.3% f: 56.7% 19-80 the positive association between the duration of facemask use and protection against ili 20** thorsten suess (2012)(38) controlled trial germany households t: 302 m: 51.6% f: 48.3% 4-43 interruption of influenza transmission within households by using a facemask 22** jenifer l. jaeger (2011)(31) cohort california healthcare personnel t: 63 m: 23.8% f: 76.2% 19–74 a significant association between using facemask or n95 respirator and seronegative and asymptomatic respiratory disease 8* chandini raina macintyre (2011)(24) controlled trial australia health care workers t: 1441 m: 9.9% f: 90.1% ≥ 18 approximately double rates of respiratory tract infection in the medical mask group compared to the n95 group among healthcare workers significant protection against cri using n95 non-fit tested arm 21** chandini raina macintyre (2009)(25) controlled trial sydney, new south wales, australia households t: 284 ≥ 0 the important role of using a facemask in preventing transmission 20** t: total, m: male, f: female, ppe: personal protective equipment, ili: influenza-like illness; hcp: healthcare personnel ; cri: clinical respiratory illness. *by newcastle-ottawa scale (nos) **by consolidated standards of reporting trials (consort) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2021; 9(1): e56 table 2: type of virus, contact, personal protective equipment (ppe), and facemask, and the number of people infected despite using a facemask in studied articles reference type of virus type of contact with an infected person ppe type (%) p_value facemask type (%) infected participants using a facemask and in contact with the patient (n) (%) taking vital signs gloves* (64.9%) taking a medical history performing a physical exam providing medication bathing or cleaning patient lifting or positioning patient amy sars-cov-2 emptying bedpan facemask (8.1%) nr** yes:8.1% no:91.9% heinzerling changing linens (2020)(16) cleaning patient room peripheral line insertion central line insertion drawing arterial blood gas drawing blood manipulation of oxygen mask or tubing manipulation of ventilator or tubing in-room while high-flow oxygen being delivered collecting respiratory specimen hyun kyun ki (2019)(32) mers touch of patient mask or respirator (52.9%) p_value<0.05 surgical mask(48.4%) p_value<0.001 yes:0.8% no: 99.1% touch of bed or equipment gloves (0.8%) p_value=0.624 n95 respirator (4.4%) patient transportation patient counseling boyeong ryu (2018)(19) mers-cov ambulance disinfection facemask (100%) n95 respirator in participants (100%) yes:2.9% no: 97.1% specimen transportation respiratory specimen collection gloves surgical mask in symptomatic patients taking vital signs discarding exposed goods other basem m. alraddadi (2016)(20) mers-cov direct contact with patient gloves (87.2%) medical mask p_value>0.05 yes:6.4% no: 93.6% gown (87.2%) p_value=0.81 aerosol-generating procedures eye protection p_value>0.05 n95 respirator p_value>0.05 facemask or respirator p_value>0.05 touching the patient gown (%100) touching the patient’s equipment gloves (%100) surasak wiboonchutikul (2016)(47) mers-cov examining clinical specimens eye protection (%100) n95 respirator (100%) yes:0% no:100% obtaining clinical specimens cap (%100) cleaning the patient’s room facemask (%100) rhinovirus influenza a (h1n1) osamah barasheed (2014)(21) influenza b dual infection (rhino & influenza a) usual contact between people in hajj facemask (45.7%) p_value>0.05 surgical mask (45.7%) p_value>0.05 yes:11.1% no:88.8% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 12 table 2: type of virus, contact, personal protective equipment (ppe), and facemask, and the number of people infected despite using a facemask in studied articles reference type of virus type of contact with ppe type (%) p_value facemask type (%) infected participants an infected person using a facemask and in contact with the patient (n) (%) parainfluenza 3 enterovirus thorsten suess (2012)(38) influenza a (h1n1) household contacts hygiene and facemask (31.4%) p_value=0.2 surgical mask (62.9%) p_value<0.05 yes:8.6% no:91.3% influenza b facemask (62.9%) 0.3 encounters gloves (71.4%) p_value>0.05 mask p_value>0.05 yes:14% no:86% exposure to respiratory secretions gown p_value>0.05 jenifer l. jaeger (2011)(31) influenza a (h1n1) exposure before institution of at least droplet precautions facemask or n95 respirator (31.7%) p_value>0.05 n95 respirators p_value>0.05 skin-to-skin contacts total ppe use (73%) p_value>0.05 adenoviruses n95 fit (32%) p_value=0.19 chandini raina macintyre (2011)(24) human metapneumovirus nr facemask (100%) p_value=0.19 n95 non-fit (33.9%) p_value=0.03 yes:1.8% no:98.2% coronavirus 229e⁄nl63 medical mask(34.1%) p_value=0.67 parainfluenza viruses 1, 2 or 3 influenza viruses a (h1n1) or b respiratory syncytial virus a or b rhinovirus a⁄b coronavirus influenza a (h1n1) facemask (65.4%) surgical mask (33%) influenza b p_value=0.19 p_value=0.32 adenoviruses daily hand wash p_value=0.21 respiratory syncytial virus chandini raina macintyre (2009) (25) parainfluenza viruses 1,2 and 3 household contacts p2 mask (32.4%) p_value=0.12 yes:8% no:92% human metapneumovirus coronavirus oc43 using soap for washing hand p_value=0.87 picornaviruses rhinoviruses enteroviruses uncharacterized no sequenced picornaviruses *these percentages were reported from 37 health care workers who were tested for sars-cov-2 and participated in interviews in this study. ** nr: not reported this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2021; 9(1): e56 table 3: quality assessments of controlled clinical trials ,based on consort item osamah barasheed (28) thorsten suess (45) chandini raina macintyre (31) chandini raina macintyre (32) 1.identification as a randomized trial in the title structured summary of trial design, methods, results, and conclusions (for specific guidance see consort for abstracts) 1 1 1 1 2. scientific background and explanation of rationale, specific objectives, or hypotheses 1 1 1 1 3. description of trial design (such as parallel, factorial) including allocation ratio important changes to methods after trial commencement (such as eligibility criteria), with reasons 1 1 1 1 4. eligibility criteria for participants settings and locations where the data were collected 1 1 1 1 5. the interventions for each group with sufficient details to allow replication, including how and when they were actually administered 1 1 1 1 6. completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed any changes to trial outcomes after the trial commenced, with reasons 1 1 1 1 7. how sample size was determined when applicable, explanation of any interim analyses and stopping guidelines 1 1 1 1 8. method used to generate the random allocation sequence, type of randomisation, details of any restriction (such as blocking and block size) 1 1 1 1 9. mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 1 1 1 1 10. who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 1 1 1 1 11. if done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how if relevant, description of the similarity of interventions 0 1 0 0 12. statistical methods used to compare groups for primary and secondary outcomes methods for additional analyses, such as subgroup analyses and adjusted analyses 1 1 1 1 13. for each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome for each group, losses and exclusions after randomisation, together with reasons 1 1 1 1 14. dates defining the periods of recruitment and follow-up why the trial ended or was stopped 1 1 1 1 15. a table showing baseline demographic and clinical characteristics for each group 1 1 1 1 16. for each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 1 1 1 1 17. for each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) for binary outcomes, presentation of both absolute and relative effect sizes is recommended 0 0 0 0 18. results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory 0 1 0 1 19. all-important harms or unintended effects in each group (for specific guidance see consort for harms) 1 1 1 0 20. trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses 1 0 1 1 21. generalisability (external validity, applicability) of the trial findings 1 1 1 1 22. interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence 1 1 1 1 23. registration number and name of trial registry 0 0 0 0 24. where the full trial protocol can be accessed, if available 0 0 0 0 25. sources of funding and other support (such as supply of drugs), role of funders 1 1 1 1 total score 20 22 21 20 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shaterian et al. 14 table 4: quality assessments of studiesbased onnewcastle ottawa study year study type selection comparability outcome amy heinzerling (17) 2012 cohort **** *** basem m. alraddadi (21) 2020 cohort *** * *** jenifer l. jaeger (32) 2012 cohort *** * *** hyun kyun ki (33) 2011 cohort ***** * *** boyeong ryu (20) 2010 cross-sectional *** ** ** surasakwiboonchutikul (48) 2016 cross-sectional *** ** ** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10 (1); e29 ph oto qu i z a 27-year-old female patient with acute nausea/vomiting and pelvic pain; a photo quiz murat ozsarac1∗, yusuf yurumez1, onur karakayali1 1. department of emergency medicine, sakarya university faculty of medicine, sakarya, turkey. received: february 2022; accepted: march 2022; published online: 24 april 2022 cite this article as: ozsarac m, yurumez y, karakayali o. a 27-year-old female patient with acute nausea/vomiting and pelvic pain; a photo quiz. arch acad emerg med. 2022; 10(1): e29, doi: https://doi.org/10.22037/aaem.v10i1.1508. figure 1: axial view of intravenous contrast-enhanced abdominopelvic computed tomography scan of the patient. 1. case presentation a 27-year-old female patient, g2p1, presented to the emergency department (ed) with acute onset nausea, vomiting, and mild chronic abdominopelvic pain. physical examination revealed bilateral lower quadrant tenderness without rebound, guarding, or rigidity, and vital signs were within normal limits. electrolytes, complete blood count, and liver and kidney function tests were normal. a pregnancy test was negative, and urinalysis did not reveal any abnormalities. no free fluid was observed in the abdominal ultrasound, and the ovaries and other intra-abdominal structures were found to be normal. the patient underwent intravenous contrastenhanced abdomiopelvic computed tomography (ct) scan (figure 1). what is your diagnosis? 2. diagnosis intravenous contrast-enhanced abdominopelviccomputed tomography (ct) scan shows dilatation in the left gonadal vein and dilated vascular structures in the left parauterine area (figure 2) in favor of pelvic congestion syndrome (pcs). the differential diagnosis of pelvic pain is broad. many etiological causes related to gynecological, gastrointestinal, urinary, vascular, nervous, and musculoskeletal systems should be considered (1). pelvic congestion syndrome (pcs) might be one of the most common, underdiagnosed causes of pelvic pain in female patients. it is also an entity not sufficiently recognized in emergency medicine practice. the etiology of congestion is quite complex due to hormonal and structural causes. valvular insufficiency, reflux, and venous obstruction play an important role in developing congestion and stasis (2). this text presents and discusses a pcs case who presented to the emergency department (ed) with abdominopelvic pain and nausea/vomiting. 3. case fate antiemetics and analgesics were administered. no intervention was performed for the patient after consultation with obstetrics and gynecology. a follow-up by the cardiovascular surgery department was planned. the control trans-vaginal ultrasound examination performed at the outpatient clinic two weeks later was evaluated as normal. no malignancy or intraepithelial lesion was observed in the cervical smear. analgesics were recommended to the patient, and symptom this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ozsarac et al. 2 figure 2: axial view of intravenus contrast-enhanced abdominopelvic computed tomography scan demonstrates dilatation in the left gonadal vein and dilated vascular structures (white arrow). follow-up was planned. 4. discussion the diagnosis of pcs does not provide a clue to to understand the underlying mechanism of disorders of the pelvic venous circulations. the clinical manifestations in pcs are chronic pelvic pain lasting longer than six months, aggravated by prolonged standing, intercourse, and menstruation, as well as lower back pain, urinary symptoms such as dysuria, urgency, frequent urination, and vaginal discharge (3). it typically affects young multiparous women between the ages of 20 and 30, although it can rarely be seen in pregnant women and during the postmenopausal period (4). pelvic varices are accompanied by lower extremity varices and chronic venous insufficiency in 10%-70% of cases. it is less frequently associated with the enlargement of thigh, perineal, vulvar and saphenous veins. particularly, the development of edema in the legs, varicose veins of the lower extremities, pain, and heaviness in the legs are directly related to the reflux that develops in common anatomical connections (5). as a noninvasive screening tool, doppler ultrasound is a reasonable initial option as it allows real-time dynamic imaging and flow evaluation. transvaginal ultrasound and doppler ultrasound criteria for pcs diagnosis include a dilated, parauterine, and paraovarian vein greater than 4 mm in diameter or retrograde flow (1, 4). color doppler in the upright position with valsalva manuver significantly increases the diagnostic accuracy (1). pcs imaging criteria for ct and magnetic resonance imaging (mri) include the presence of at least four ipsilateral coiled parauterine vessels or an ovarian vein diameter greater than 8 mm (4). ct and mri are better diagnostic tools than ultrasound as they provide a detailed anatomical examination of dilated pelvic and ovarian veins. however, ct and mri cross-sectional images obtained in supine position play a limited role in diagnosing pcs and detecting dilatation of the thin pelvic veins (6). once the diagnosis is confirmed, pcs management includes medical, surgical, and endovascular approaches. different treatment modalities have been tried for embolization of abnormal pelvic veins, providing symptom relief in 75% of patients (5). 5. conclusion contrast-enhanced ct scan may provide an incidental diagnosis of pcs in patients with frequent presentations due to pelvic pain. however, the diagnosis can be easily overlooked unless doppler ultrasonography is performed in the semisupine or upright position. emergency physicians must recognize this common but overlooked clinical condition. 6. declarations 6.1. acknowledgements we would like to thank lingus and bsb group for english language editing. 6.2. conflict of interest the authors declare no conflicts of interest. 6.3. funding and support none. 6.4. authors’ contributions all authors met the criteria for authorship contribution based on the international committee of medical journal editors’ recommendations. 6.5. informed consent for publication the photo quiz was written in an anonymous characteristic, thus confidential and detailed data about the patient is removed. editor and reviewers can know and see these detailed data. references 1. bendek b, afuape n, banks e, desai na. comprehensive review of pelvic congestion syndrome: causes, symptoms, treatment options. curr opin obstet gynecol. 2020;32(4):237-42. 2. gavrilov s, moskalenko yp. does pelvic congestion syndrome influence symptoms of chronic venous disease of the lower extremities? eur j obstet gynecol reprod biol. 2019;243:83-6. 3. liu j, han l, han x. the effect of a subsequent pregnancy after ovarian vein embolization in patients with infertility caused by pelvic congestion syndrome. acad radiol. 2019;26(10):1373-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10 (1); e29 4. bartl t, wolf f, dadak c. pelvic congestion syndrome (pcs) as a pathology of postmenopausal women: a case report with literature review. bmc women’s health. 2021;21(1):181. 5. basile a, failla g, gozzo c. pelvic congestion syndrome. semin ultrasound ct mr. 2021;42(1):3-12. 6. borghi c, dell’atti l. pelvic congestion syndrome: the current state of the literature. arch gynecol obstet. 2016;293(2):291-301. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem case presentation diagnosis case fate discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 52 emergency (2016); 4 (2): 52-54 letter to editor central venous pressure monitoring; introduction of a new device mahmood ghafoori yazdi1, arya shoghli1*, sina faghihi1, alireza baratloo2 1. faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: arya shoghli; faculty of medicine, shahid beheshti university of medical sciences, evin, tehran, iran. post code: 198396-3113, email: arya_sh89@yahoo.com received: july 2015; accepted: august 2015 to the editor: entral venous pressure monitoring hemodynamic monitoring is needed in up to 58% of patients presented to the emergency department (1). although central venous pressure (cvp) monitoring is generally useful to assess general volume status, its reliability as a guide to resuscitation in critically ill patients is a subject of debate (2, 3). generally, there are several methods of cvp measurement, which can be categorized as invasive and non-invasive. currently two methods are available for direct and invasive measurement of cvp. in the first method, after fixing a cv line catheter, cvp is measured using a cvp manometer connected to patient’s cv line. in the other method, an electronic transducer, connected to the cv catheter from one side and to the digital monitor from the other, is used to demonstrate measured cvp. there are also non-invasive methods such as direct observation and ultrasonography, which are used for indirect measurement of cvp. observation of internal jugular venous pulsation remains an acceptable method to estimate right atrial pressure (4). in addition, ultrasonography can be used to determine elevated jugular venous pressure (5). if the jugular vein appears larger than the adjacent common carotid artery when the patient is in a semi upright position, cvp is probably >10 cmh2o. another method of measurement is plethysmography. change in forearm volume in response to externally applied pressure to upper arm veins is an indicator of cvp measure (6). forearm volume may be measured by mercury-in-silastic strain gauge plethysmography. the correlation between cvp measured by this technique and invasive cvp is about 0.97 (7). all the mentioned methods have some negative points. using a manometer, is time consuming and may be affected by operator errors. using a transducer is expensive (about 25 dollars for each patients in iran) and requires the patient to be in a stable, calm environment in order to provide a more accurate measurement. in addition, non-invasive methods may be inaccurate since they measure the cvp indirectly and can render variable results depending on the operator. considering the abovementioned, here we introduce a new device that can facilitate cvp measurement and provide physicians with further accurate data that can be helpful in decision making and patient management. electronic continuous cvp monitoring device this new device (figure 1) uses a sensor to measure cvp, by calculating the pressure difference between cv line catheter and the atmosphere. the device is equipped with a liquid crystal display (lcd), which shows time and date, cvp at the moment, mean cvp, and variance. the pressure sensor is fixed at the bottom of the device and has two openings, one is connected to the cv line using an appropriate plastic tube, and the other remains free to measure the atmosphere pressure for comparison. the device has a secure digital (sd) memory card slot, which keeps records of all the measured data for the patient. the device needs to be connected to a power source to receive the 12 volts needed for its functioning. with the patient lying flat in supine position, the device is held at the level of right atrium. the designed sensor is connected to the cv line using an appropriate plastic tube. cvp is measured twice per second, and the measured cvp at each moment appears on the lcd. the device is equipped with an alarm system, which sets off if the measured cvp is lower or higher than the defined range. mean cvp value is calculated automatically and shown on the lcd, and gives the physician an estimation of the patient’s status since the time of connection to the device. variance is also calculated and shown on the lcd, and if it is wider than a pre-defined range, it may be a sign of clogging of the line and the alarm sets off. compared to other available methods a number of adc this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 53 emergency (2016); 4 (2): 52-54 vantages can be pointed out for this device. the electronic continuous cvp monitoring device is relatively small, which makes it very portable and easy to use on different patients. it can measure cvp within seconds, which leaves more valuable time to provide care for critical patients. this method will also cost much less for the patients, since it only uses a simple plastic tube for connecting to the cv line. furthermore, all the data will be saved on an sd card, which will be given to the patient and can be used in the future as a part of the patient’s medical profile. once the device is connected, it will measure the cvp twice per second continuously, while calculating the mean cvp and variance, a feature lacking in previous methods which is crucial for evaluating patient’s progress during treatment and plays an important role in decision making. the alarm system is another notable advantage which can make a huge difference in a crowded er, helping physicians to avoid missing a patient in critical condition. clinical testing the device was tested on 11 patients in emergency departments of 3 different hospitals in tehran, iran, for whom cv line catheter had been fixed. cvp was measured by conventional manometer method, and immediately afterwards by the electronic device. the difference between values measured by two methods was not clinically significant. future outlook the device needs to be tested on more patients and results need to be taken into account after using larger sample sizes in the future, in order to calibrate the device for maximum accuracy. the results should also be compared to those measured by the monitor connecting transducer, as it may be a more reliable method than cvp manometer. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. nawar ew, niska rw, xu j. national hospital ambulatory medical care survey: 2005 emergency department summary. adv data. 2007 (386):1-32. 2. landis e, brown e, fauteux m, wise c. central venous pressure in relation to cardiac “competence,” blood volume and exercise. journal of clinical investigation. 1946;25(2):237. figure 1: electronic continuous central venous pressure (cvp) monitoring device. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com ghafoori yazdi et al 54 3. marik pe, baram m, vahid b. does central venous pressure predict fluid responsiveness?: a systematic review of the literature and the tale of seven mares. chest journal. 2008;134(1):172-8. 4. constant j. using internal jugular pulsations as a manometer for right atrial pressure measurements. cardiology. 2000;93(1-2):26-30. 5. drazner mh, rame je, stevenson lw, dries dl. prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. new england journal of medicine. 2001;345(8):574-81. 6. lipton b. estimation of central venous pressure by ultrasound of the internal jugular vein. the american journal of emergency medicine. 2000;18(4):432-4. 7. ward kr, tiba mh, barbee rw, et al. a new noninvasive method to determine central venous pressure. resuscitation. 2006;70(2):238-46. archives of academic emergency medicine. 2023; 11(1): e13 or i g i n a l re s e a rc h comparing the emergency medicine residency programs in iran and around the world; a descriptive study mahdi talebi1, morteza talebi doluee2, mohamadali jafari3∗, hamid zamani moghaddam2, mahdi foroughian2, mojtaba moazzami4, hassan gholami5, hamidreza reihani2 † 1. department of community and family medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. emergency department, shahid sadoughi hospital, shahid sadoughi university of medical sciences, yazd, iran. 4. department of educational management, north tehran branch, islamic azad university, tehran, iran. 5. department of medical education, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: to identify the strengths and weaknesses of emergency medicine residency curriculum in iran, and to benefit from the experiences of successful universities, comparative studies are crucial. this study compared the components of the national curriculum of emergency medicine in the united states, canada, the european union, australia, and saudi arabia with iran. methods: data for this research was collected by searching the websites of different universities and also contacting them for requesting curriculums. the leading countries in emergency medicine and one of the countries in the middle east region (saudi arabia) along with the world federation of emergency medicine were selected as the sample. the model used in this field is a range model that identifies four stages of description, interpretation, proximity, and comparison in comparative studies. results: in the curriculum of the united states, canada, the european union, australia, and saudi arabia, there were lots of similarities in expressing the general characteristics of the curriculum, mission elements, vision, values, and beliefs of the discipline, educational strategy, techniques, expected competencies, rotation programs, and evaluation method, which were also similar to the iranian curriculum. however, the duration of residency for emergency medicine in iran is three years, which is shorter than other countries. as expected, the number and duration of rotations are less than other countries. also, the process of entering into this field is different in iran and is based on an exam for entrance, while most other countries use self-requested residency program. conclusion: considering the results of comparing the iranian curriculum with the curriculums of the united states, canada, the european union, australia, and saudi arabia, it seems that iran’s program is comprehensive and complete; but, a reappraisal of the course duration and entering options are necessary to eliminate or improve the inadequacies. keywords: comparative study; curriculum; education; internship and residency; emergency medicine cite this article as: talebi m, talebi doluee m, jafari ma, moghaddam hz, foroughian m, moazzami m, et al. comparing the emergency medicine residency programs in iran and around the world; a descriptive study. arch acad emerg med. 2023; 11(1): e13. https://doi.org/10.22037/aaem.v11i1.1867. ∗corresponding author: mohamadali jafari: emergency department, shahid sadoughi hospital, shahid sadoughi university of medical sciences, yazd, iran. tel: +985138525312, orcid: https://orcid.org/0000-0002-3171-6453. † corresponding author: hamidreza reihani ; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: +985138525312, email: reihanihr@mums.ac.ir, orcid: https://orcid.org/0000-0003-0617-9374. 1. introduction the residency program in clinical specialties is one of the higher university education courses, through which eligible applicants with a doctor of medicine degree can achieve their specialist degree after passing the residency exam, theoretical and practical training courses, and the exams (formative and final) (1). emergency medicine is a clinical specialty that evaluates, resuscitates, stabilizes, diagnoses, and cares for patients with emergency conditions. this specialty inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 2 cludes basic medical science, necessary clinical knowledge, appropriate skills for diagnosis, decision making, and treatment of patients referred to the emergency department, as well as handling emergencies in the inpatient ward. the specialist in this field should also be able to work as an effective member of the medical team with specialists in other fields as well as the pre-hospital emergency system (2). the founders of emergency medicine in iran, collected and analyzed about one hundred educational lesson plans related to emergency medicine in different countries (america, canada, england, australia) and the conditions of providing emergency services in many parts of the world, and finally drafted and announced the plan, in 2001. a team of 8 specialists were selected and sent to the united states for a supplementary course of emergency medicine, and in a very intensive program with the coordination of george washington university, they succeeded in completing the fellowship course in emergency medicine and later started educational residency programs in iran (2). currently, a national emergency medicine training program is available or underway in more than 35 countries. in iran, in 2001, iran university of medical sciences and later, in 2004, tehran and shahid beheshti universities of medical sciences, have launched the residency program and started accepting residents in emergency medicine. at the moment, the total number of universities with specialized fields of emergency medicine is fifteen (2). universities are obliged to train graduates capable of disease prevention and treatment, and public health improvement (3). systematic and comprehensive teaching programs (curriculum) that are consistent with the healthcare system requirements are pillars of this training (4). curriculum evaluation is an integral part of assessing the training programs in the ministry of health, treatment and medical education. medical training programs need to be constantly reviewed and efforts should be made to improve them by eliminating shortcomings (4, 5). given the vast changes that are taking place in the field of health and clinical sciences, it is certainly not possible to meet the professional needs of clinical jobs in today’s world with a traditional curriculum (5). the need for change in education is so obvious that experts have already rejected the question “is change necessary?” and believe that the question should be "what changes are necessary? " (6). according to the researches, educational administrators and programmers should modify their curriculum based on goals and continuous evaluation so that students receive sufficient scientific and educational care. they should also review and revise subjects in which students’ ability is reported to be poor (7). one of the research methods for updating the educational programs is the conduction of comparative studies. a comparative study is a practice in which two or more phenomena are put together and their differences and similarities are analyzed (8). comparative studies are a rational strategy for using the experiences of other universities. by coordinating their information and programs with the financial conditions and local and indigenous considerations of our country, better programs can be developed so that human and financial resources can be used in more efficient ways (9). in almost all societies, educational issues and goals are similar, but methods and planning are different. educational methods, planning, and problem-solving in each society are related to their tradition and culture (10). therefore, numerous comparative studies have been conducted to compare the curriculum of different countries in primary medical education (11, 12), laboratory sciences (8), internal medicine (13), educational planning (14), and science education (15). due to the stated needs and knowledge gap regarding the comparative comparison of the emergency medicine curriculum, this study is performed for preparing the prerequisites and backgrounds for modifying the emergency medicine curriculum in iran. the purpose of this study is to compare the specialized curriculum of emergency medicine in iran and selected universities from around the world to compare the different areas and dimensions of the emergency medicine curriculum. 2. methods 2.1. study design and settings this is a cross-sectional with comparative design, which has been approved by the vice-chancellor for research of mashhad university of medical sciences, mashhad, iran, (code: 950021). the literature used for this study was reviewed from january to march 2022. the researchers first visited the websites of different universities and then contacted the university for their emergency medicine specialty training program. then, they consulted with some members of the board of emergency medicine, and some of the universities that fitted the purpose of this study were selected. 2.2. data gathering in this selection, an attempt was made to select a sample from different parts of the world, especially neighboring countries. specialized medical training programs, especially emergency medicine, in each part of the world have a special eye for the needs of the people of the region, and these needs are completely different from one country to another and from one region to another. eventually, the united states, canada, the european union, australia, saudi arabia, and the world federation of emergency medicine, which is homogenous with many other curriculums, were selected. another point is the selection of prototype programs approved by the educational program accreditation organizations in each country, and no attention has been paid to the minor changes that each university may make in these this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e13 programs. since the variables required for the study may not be completely consistent with predetermined patterns such as the range model, in addition to considering the range model, which includes four stages of description, interpretation, proximity, and comparison (11-16), some considerations have been made based on their importance from the viewpoint of the members of the specialized board of emergency medicine. the selected curriculums were fully studied. in the next step, a table was prepared and drawn for each element of the educational program, and the names of the studied universities were placed in rows. thus, the information about each university was organized. then the similarities and differences in each element of the program between all the studied universities were gathered; and finally, based on these similarities and differences, a practical proposal was presented to improve each of the elements in the iranian curriculum. the collected variables were emergency medicine description scale, emergency medicine interpretation scale, emergency medicine proximity scale, emergency medicine comparison scale, course venue, and name of the country whose university curriculum is reviewed, values and beliefs, mission and vision, general objectives of the field, expected competencies, professional role and duties of graduates, educational strategy, teaching methods and techniques, conditions and manner of student admission, student evaluation, course length, and courses rotation. 2.3. statistical analysis there are no quantitative data in this study with no statistical analyses. 3. results the separate results for each of the elements of the curriculum are presented here: 3.1. introduction to the course (field) table 1 shows the introduction of the course and the curriculum in each of the studied educational programs. the similarities extracted from the curriculums are: the program in all universities has shown the importance of this field as a clinical specialty and the effective role of emergency medicine in the diagnosis, treatment, and management of patients with acute unclassified problems at all ages. others include the managerial role of emergency medicine specialists in the management of the emergency department as well as pre-hospital emergencies. on the other hand, there is no major difference between curriculums. 3.2. values and beliefs, mission and vision values and beliefs, mission and vision in each studied curriculum are expressed in table 2. since the curriculum in iran is based on the strategic planning model, the elements of mission, vision, and values for the field of emergency medicine can also be seen in the curriculum in iran, which is similar to the united states and canada. also, in all curriculums, the purpose of establishing the field is to train capable forces in order to meet the urgent needs of patients. by studying the mission of american, canadian, and iranian universities, we can realize the core of this mission. on the other hand, there was no section as, vision and values in the eu curriculum mission. also, in the saudi and ifem program, this issue was only described in a brief paragraph. the canadian curriculum also makes good reference to the individual competencies of emergency medical professionals. the evaluated curriculums did not directly address the category of research. 3.3. general goals the overall objectives in the field of emergency medicine curriculum of each studied university are shown in table 3. in all cases, the overall goal statement focused on the final result of the course and the training of specialized personnel. also, all curriculums have mentioned the importance of preparing manpower graduating with the necessary skills and ability to deal with crisis and manage the emergency department. however, the australian curriculum does not set goals separately and goals in the saudi and eu curriculums are mentioned very briefly. 3.4. expected capabilities, roles, and professional duties of graduates the expected competencies, roles, and professional duties of the graduates in each of the studied curriculum are shown in table 4. competencies are similar in different curriculums and are based on medical knowledge, proficiency, communication with colleagues, the ability to work in a team, having the commitment, and sometimes research. based on these capabilities, the curriculum framework is prepared by the accreditation organizations of each country. the differences are brief, and in each curriculum, one of the mentioned values may be less prominent. 3.5. role and professional duties of graduates table 5 shows the professional roles and responsibilities of graduates in each of the studied curriculums. information about the role of specialists and expected competencies are mentioned in a combined and undifferentiated manner in different parts of the curriculums. in general, all curriculums, directly or indirectly, emphasize the training of a capable specialist who has the ability to manage critically ill patients. in addition, their managerial role inside and outside the hospital has been emphasized. the research and educational role of specialists also had a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 4 place in all curriculums. the difference between the curriculums in this respect is clear. however, we can say that some differences exist in the intensity of emphasis or reference to research and educational role place in the curriculum. 3.6. educational strategy in some curriculums, training strategies (table 6) are not discussed separately, so it may be best to combine the training strategy section with training methods and techniques. in the iranian curriculum, these two parts are listed separately, so they are mentioned separately in this study. in the different curriculums, there is an unorganized reference to personal learning, central teacher, providing learning opportunities, giving feedback, and so on. despite the use of different words in the study of all curriculums, it seems that all these cases have been considered. the curriculum in the united states, australia, and europe have not specifically addressed this issue and it has been addressed under the heading of teaching methods and techniques. 3.7. teaching methods and techniques, study method (virtual face-to-face) it should be noted that this section includes two separate elements of teaching methods and techniques and study methods (table 7), which are expressed together due to overlap in the different curriculums. in some curriculums, even educational strategies are given in this section. in all curriculums, teaching methods and techniques are very similar as follows: different methods of clinical education, skills training, classroom combination, lectures, group learning, journal club, etc. on the other hand, in the european curriculum, educational techniques have not been specifically addressed. some curriculums, such as australia, also place more emphasis on e-learning. 3.8. conditions and manner of student admission (entry conditions) table 8 shows the conditions and manner of student admission (entry conditions) in each of the studied curriculums. in saudi arabia, as in iran, residents are selected through entrance exams. in studied countries other than iran and saudi arabia, individuals were selected based on the candidate’s request and review of his/her records and the opinion of the residency director. 3.9. student assessment in all universities, very different methods have been considered for the developmental and general evaluation of residents (table 9), including theoretical and practical tests, reviewing the performance of residents in the workplace and simulated environments, the opinions of colleagues and staff, reviewing files, etc. attempts have been made not to be satisfied with a few limited methods and to make the evaluations as objective as possible. on the other hand, there are so many differences in all aspects of evaluation that no specific difference can be pointed out. in the american curriculum since 2008, when the milestone project was launched, the focus was on assessing the ability of residents as a criterion for the success of the course. seventeen competencies were considered as the main competencies for each category of residency (for example, at the end of the first year of residency) and the level of competency was determined based on objective criteria. the resident must have reached this level of capability in order to be promoted to a higher year. 3.10. the length of the specialized course of emergency medicine as table 10 shows, in some american emergency medicine centers the duration of the course is 3 years, just like in iran. while in canada and australia it is a 5-year period; in the us, saudi arabia, and based on ifem recommendation it is a 4year period. in the eu it also varies from one country to another but it is at least 5 years. 3.11. number and manner of emergency medicine rotations in the emergency medicine course, rotations play a major role in empowering residents. on average, half of the courses are spent on rotations. some of these rotations, such as anesthesia, pediatrics, intensive care, and internal medicine, are particularly important. in all programs, there is a lot of emphasis on rotations and their educational role (table 11). important rotations are the same in all programs and include anesthesia and intensive care, pediatrics, surgery, orthopedics, gynecology, and psychiatry. in some programs, like in iran, a pre-hospital emergency period is defined. on the other hand, depending on the variety of patients in the emergency room, the duration of rotations in different programs is defined differently. the choice of rotations is left to universities to some extent. in saudi arabia, hajj rotation is considered. in iran, the duration of rotations is between 12 to 18 months of the residency period. 4. discussion this study aimed to compare the medical emergency residency curriculum of iran with some other countries by matching each element of the curriculum. the similarities of the curriculums in iran with other countries were highlighted. the fact that america has been the leading country in the introduction and development of this field is undeniable. emergency medicine is not as old as other medical fields. therefore, it seems that all curriculums have been this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e13 adopted from american ones. according to the gathered results, it seems that the emergency medicine curriculum is very similar to other curriculums in the first world countries and ifem in terms of its components. therefore, it seems that except for the duration of the course, which is shorter in iran than in other countries, it has no problems and lapses. the approval of the emergency medicine program by the world federation is another reason for this claim. here, in addition to the physical examination, other components of the curriculum were reviewed again in a much more detailed manner. 4.1. the definition emergency medicine is a series of clinical expertise that in addition to the therapeutic role, deals with position management, planning, and dealing with crises. these cases in the iranian curriculum, like other investigated curriculums, are quite clear and prominent. 4.2. values and beliefs, mission and vision providing quality and patient-centered services in terms of medical emergencies for all ages and all cultural and racial strata in society with an emphasis on patient prioritization, as well as training of specialized human resources and emphasis on lifelong learning were common to all curriculums. 4.3. general objectives of the field graduation of capable forces in accordance with the needs of society, which is the same in all curriculums. 4.4. expected capabilities organizations that evaluate the accreditation of educational programs in different countries of the world have considered different frameworks for the curriculum of specialized disciplines, which are called curriculum frameworks in textbooks. in the united states, this is the responsibility of accreditation council for graduate medical education (acgme), in canada, canmed is in charge and there is a similar pattern in the european union and australia. in iran, this task is the responsibility of the secretariat of the specialized council of the ministry of health. the expected capabilities mentioned in the iranian curriculum, like all specialized curriculums of other medical fields in iran, are exactly copied from the acgme. therefore, there are similarities between the iranian curriculum and other curriculums. in the case of skill competencies in the iranian curriculum, skills are mentioned in two sections. the first one is a mandatory two-part section and the other one is the skills that are good to know. in other curriculums, including the american curriculum, a series of competencies have been considered as core competencies and other capabilities have been considered as ancillary skills. in this respect, there are similarities. 4.5. role and professional duties of graduates for this aspect, the iranian curriculum has dedicated a part to this headline and has introduced a position of care, education, management, and research as the roles of graduates. although not explicitly stated in some curriculums, this is the case for all graduates. 4.6. educational strategy and teaching methods and techniques due to the pervasiveness and modernization of medical education, new educational principles have been considered in the iranian curriculum and universities, so there is no difference between iran and other countries in that manner. 4.7. terms and conditions of student admission in this part, there is a big difference between iran and other countries. in iran, the criterion for acceptance is only the score obtained in the residency exam, while in other countries, universities have the right to select a resident through a review of records and interviews, which seems necessary in the field of emergency medicine. 4.8. student evaluation in this aspect, just like the educational methods in our country, the latest methods of clinical evaluation of students are used and we are not different from the developed countries. since 2008 a new way of assessing the ability of residents has been introduced in the united states. for each level of residency, a desirable level of competence was defined and the resident must have reached this level. in fact, evaluation is consequential and it does not matter if the course has been taken up or not. given the importance of empowering graduates in this field, it is appropriate to use this method for evaluation in iran. 4.9. course length according to the policy of the ministry of health, for faster training of specialists, the duration of the course is currently 3 years, and it is hoped that the length of the course will be increased to enrich the training program. 4.10. number and method of rotations defined based on the composition of the patients who visit the emergency ward, these rotations are common to almost all curriculums. for other fields, curriculum matching has been done, some of which are mentioned here. karimi monaghi and sadghat (12) working on the study of dermatology curriculum, showed that the key elements of this curriculum are similar to the curriculum of the world’s top universities. in this respect, it is similar to the emergency medicine resithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 6 dency program. the difference between the iranian dermatology curriculum and the world was also the method of entering this program, in which all iranian residency programs are different from the world. in a similar study, karimi monaghi and colleagues (12) compared the master’s degree program in medical education in iran and some countries in 1991. based on the results of matching iranian curriculum with dundee, maastricht, and calgary universities, it seems that the iranian program is comprehensive and complete, but to eliminate the shortcomings and improve it, it was suggested that the educational goals and strategies be reviewed. the course should be presented both online and in person. the admission of undergraduate courses and lack of skills should be covered under the prerequisite courses, such as courses provided for further study and research methods in education. due to the novelty of the medical education curriculum and its compilation by medical education specialists, the curriculum of this field can be used to review and eliminate the problems and weaknesses of the field of emergency medicine. in another study, kermanshahi and colleagues compared the training program for master of nursing in iran and canada in 2010 and concluded that the programs should be modified in terms of setting the philosophy, goals, and mission of nursing education at a complementary level so the tasks designed for the nursing program should be related to the field, realistic and in harmony with the philosophy, mission, and perspective of the field (6). haj bagheri (17), in a different study, has compared the philosophy, goals, and curriculum of advanced levels of nursing education in iran and the world and concluded that nursing education program does not fit the needs of the society based on philosophy, goals, and written mission and lacks the necessary quality. according to the role and duties of nurses in health systems, practical programs and strategies can be set in different areas of nursing (7). since the master’s degree program in nursing has not changed significantly since 1995, major changes are needed to improve it. also, the curriculum of advanced levels of nursing education in 2002 needed serious reforms. however, due to its freshness and up-to-dateness, the emergency medicine residency program has minor problems and does not require major changes. on the other hand, since the emergency medicine curriculum is written by experts in this field, it is expected that the necessary points and principles be observed in compiling the program and paying attention to the professional duties of graduates. in 2006, mollainejad and zakavati (18), in another comparative study of teacher training education curriculum in the united kingdom, japan, france, malaysia, and iran, presented these strategies to improve the iranian teacher training education system: combining theory and practice, balancing theory and practice, development of teacher training standards, integration of information and communication technology in the program, communication between preservice and in-service training, and coordination between management institutions (9). these strategies can be justified considering the antiquity of the teacher training curriculum in iran. in a comparative study by jafari harandi and colleagues, science education curriculum in iran and several countries were compared in 2009 and it was concluded that there are significant similarities and differences between the objectives, content, teaching method, and evaluation method between the studied countries and iran. the similarities are more in the goals and content and the intended curriculum, but the differences are more in the teaching methods and evaluation methods (15). in the present study, many similarities were observed in all objectives, content, teaching methods, and evaluation methods, and there was not much difference except for the duration of the course. in 2009, in a comparative study by dargahi and colleagues (19), e-learning in the field of medical sciences in selected countries was compared. the results of their study showed that the e-learning system in iran’s medical universities has shortcomings compared to the leading universities and the success of this system requires the establishment of technological and cultural infrastructure and improving the skills required by users (8). a new e-learning system has been established in iran following the example of other countries, so in order to improve and strengthen the system, it is necessary to use their experiences. mirza mohammadi (20) has conducted a study entitled "comparative study of the doctoral curriculum in the field of curriculum planning in iran with foreign universities" and based on the comparison between iran and some worldfamous universities in this field, he suggested strategies to improve the curriculum of the doctoral program in the field of curriculum planning in iran. in these strategies, it is observed that in the doctoral program in the field of curriculum planning, fundamental reforms should be made in the research department and it should be considered as an independent chapter, especially considering that the focus of research in the field of the curriculum is mainly quality. from the experiences of foreign universities studied in their research, the basics, methods, and principles of qualitative research can be taught to students in this field in iran. this solution is similar to the results of the present study, but in another solution obtained from mirza mohammadi’s study, it is stated that the breadth and depth of specialized subjects in the curriculum of the doctoral course in curriculum planning in iran are weak and needs to be corrected or internships should be created. the internship is an inevitable necessity in curriculum planning for iranian students (10). however, these problems were not observed in the emergency medicine residency training program, and this in itself indithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e13 cates the evolution of the emergency medicine curriculum. in the end, it is worth mentioning that the requirement of any educational program is “activity” expressed as practice (21). it is hoped that by creating favorable conditions and contexts, the existing problems and shortcomings will be eliminated and repaired, and with the full and flawless implementation of the emergency medicine residency curriculum, its goals will be achieved. 5. limitation one of the limitations of this study was considering a small number of emergency medicine curriculums. curriculums from turkey, south america, and africa were also collected, which unfortunately were not usable due to the lack of an english version. since in many countries, including iran, the ministry of health curriculum is standard and only parts of it need to be completed by specialists, there is a so-called curriculum framework; it is suggested that a study is needed to compare these frameworks. another suggestion is to consider the possibility of changing the approach of evaluation and programming in a study, considering the success of an outcome-oriented curriculum and the implementation of the milestone project. 6. conclusion given that the field of emergency medicine is almost an emerging field in iran and its curriculum has been newly modeled on curriculums from reputable universities, no major troubles or problems have been observed in the iranian curriculum, but the results of this study can help the authors and curriculum modifiers in the field of emergency medicine and other similar fields in iran to have a broader view of the development, revision, and modification of the curriculum and more appropriate selection of objectives, content, teaching methods, evaluation, and other components of the curriculum. 7. declarations 7.1. acknowledgments not applicable. 7.2. funding source no funding was obtained for this study. 7.3. authors’ contribution the 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student’s knowledge about triage. proceeding of the 3th international congress of cure and health and crisis management in disaster; 2007. 21. definition of em 2017 [available from: https://www.acep.org/clinical—practicemanagement/definition-of-emergency-medicine/. 22. caep definition of emergency medicine 2016 [available from: http://www.caep.ca/sites/caep.ca/files/caep/position_ statement_on_emergency_medicine_definitions.pdf. 23. em definition 2017 [available from: https://acem.org.au/structured-documents/qualitystandards/glossary-of-terms.aspx. 24. em definition 2017 [available from: https://acem.org.au/structured-documents/qualitystandards/glossary-of-terms.aspx. 25. mission and vision of acep 2017 [available from: https://www.acep.org/aboutus/mission/. 26. misson & vission & values 2017 [available from: https://medicine.dal.ca/departments/departmentsites/emergency/about/mission-vision.html. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e13 table 1: introduction of the course in the studied curriculum country introduction to emergency medicine usa emergency medicine is a clinical specialty that diagnoses and treats diseases and unforeseen injuries. emergency medicine includes all the knowledge required in the clinical model of emergency medicine. emergency medicine works include initial assessment, diagnosis, treatment, coordination of patient care among several service providers, and assignment of each patient who needs further medical, surgical, or psychiatric services. emergency medicine provides medical planning, foresight, and guidance for social medicine response, medical control, and health crisis. emergency medicine professionals provide valuable clinical, administrative, and managerial services to the emergency department and other parts of the health care delivery system (22). canada emergency medicine is a discipline of medicine that includes a unique set of capabilities to evaluate, diagnose, treat, and assign tasks to all patients with injuries, illnesses, and/or behavioral disorders that require prompt care at all times (365/7/24). these conditions are often vague and include life-threatening, acute, and urgent cases (but not limited to these). this care is typically provided in a hospital; however, the scope of emergency medicine goes beyond the emergency department (23) european union emergency medicine is a medical specialty based on the knowledge and skills necessary to prevent, diagnose, and treat all diseases, emergencies, and injuries that affect people of different ages, as well as unclassified physical, behavioral, and psychological causes. this specialty is responsible for pre-hospital and hospital admissions, resuscitation, and management of all patients with emergency conditions, as well as patients who enter the emergency department with an unknown diagnosis until discharge or transfer to another specialized service. it is also responsible for establishing and managing the hospital and pre-hospital emergency systems. emergency medicine is an interdisciplinary specialty and has a strong connection with other specialized disciplines. emergency medicine is a complementary field. australia emergency medicine is a field of medicine that is classified based on the knowledge and skills necessary to prevent, diagnose and manage the acute and immediate aspects of diseases and injuries in patients of all age groups with a wide range of physical and behavioral problems. besides, emergency medicine can’t just be summarized in pre-hospital and hospital emergency systems (24). saudi arabia emergency medicine is a clinical specialty that treats a wide range of diseases and acute injuries in all age groups. an emergency medicine specialist is primarily a clinician who uses high levels of clinical decision-making skills to care for acute patients and unclassified medical problems, often before complete diagnostic and laboratory information is available. an emergency medicine specialist is an academician in the community field who pilots the emergency department function, medical emergency systems, and programs, , as well as education and research in this field, intending to promote knowledge and improve the consequences of individual and social health. definition of emergency medicine specialist: our emergency medicine specialist is the yield of a combination of medical knowledge and clinical skills. in addition to gaining skills in medical knowledge, they show their deep attitude and understanding of different clinical scenarios. they are not just emergency physicians, but diagnosticians, scholars, teachers, professors, interveners, and artists. however, emergency medicine professionals, like any other specialist in any field, are fully skilled in everything they do. their main skill is in risk classification. iran emergency medicine is a clinical specialty that evaluates, resuscitates, stabilizes, diagnoses, and cares for patients referred to the emergency department. this specialized field includes basic science information and necessary clinical knowledge and appropriate perceptual and technical skills for diagnosis, decision making, and treatment of patients referred to the emergency department, as well as emergency department management and emergencies. experts should also be able to contribute as a member of the medical team with specialists and cooperate pre-hospital emergency system. ifem emergency medicine is a range of clinical medicine based on the knowledge and skills needed to prevent, diagnose, and manage the acute and immediate aspects of illness, covering all age groups and covering a wide range of unclassified physical and behavioral problems. besides, it provides an understanding of the performance of pre-hospital and hospital emergency systems and the functional skills in this system. ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 10 table 2: values and beliefs, mission and perspective in the studied curriculum country values and beliefs, mission and vision usa mission statement of the american college of emergency physicians (acep): the acep offers the highest quality of emergency care and is the main advocate for emergency physicians, their patients, and the public. vision statement: emergency medicine is recognized and valued as an essential public service. patients seeking emergency care are treated by certified emergency physicians who are supported in their practice with all the resources necessary to provide the highest quality medical care. emergency physicians work in an environment where their rights, safety, and health are guaranteed. all patients have health care coverage that ensures access to emergency services. legally, health care services are fully provided. resources for the education of emergency physicians are sufficient to meet the needs of the workforce of this specialty. emergency physicians are known and valued for their commitment to patient care, education, leadership, research, and innovation. all emergency physicians are members of the acep (25). canada mission statement to save lives through patient-centered emergency care that is being transformed by educational innovations and clinical research. vision improving health outcomes for patients of all ages through research, education, and pioneering emergency medicine. values integrity: we are committed, reliable, trustworthy, and we act in accordance with our values. evidence-based decision making: we retrieve, evaluate, integrate, and measure knowledge in order to care for the patient and design a decision-making system based on the patient’s social/cultural values. accountability: we take responsibility for our actions, follow through on our commitments, and meet patients’ expectations. support: we speak for the benefit of the patient and the population, and strive for effective changes in health care providers and policymakers. collaboration: we participate in resolving interdisciplinary issues through dialogue, mutual respect, mutual trust, and integrated action. initiative: we have the ability to powerfully plan or change what is wrong with ourselves, our department, or our system. critical thinking: we systematically and continuously evaluate thinking for clarity, accuracy, bias, accuracy, logic, and relevance. professionalism: we are committed to the health and well-being of individuals and society through ethical action, respect, cooperation, and transcendent standards of conduct (26). european union not mentioned australia outlook: australian college of emergency medicine (acem), is a trusted organization to provide professional and educational clinical standards in predicting the quality of patient-centered emergency care. mission: excellence in providing quality emergency care to the community through committed and expert members saudi arabia mission: training of young specialists to provide emergency medical services, in accordance with international standards, with compassion for patients with acute problems, to learn to strive for professional and academic excellence, to be filled with personal pride and joy; and nurture leaders and professors in this branch of medicine. iran philosophy (values and beliefs): the values that govern this program are: 1. accepting the issue of health in all its dimensions as a fundamental human right 2. respect for the independence of individuals in making decisions about themselves 3. provide services to patients of any age, gender, race, religion, and social status 4. emphasis on professional and social ethics in all dimensions 5. emphasis on general priorities 6. emphasis on the spirit of searching for knowledge and lifelong learning outlook: in the next ten years, emergency medicine will be prominent in the fields of observing educational standards, producing knowledge, providing quality services, and producing science and research in the region. mission: acceptance of clinical readiness, judgment, and technical skills to be able to apply in the emergency medicine profession, to acquire and apply new knowledge and skills, and to be able to monitor their own and others’ physical and mental well-being and health. ifem outlook: creating an international curriculum model for the training of emergency medicine specialists by the world federation of emergency medicine. this curriculum model is designed on the basis of the collective agreement and provides the minimum requirements for the formation and graduation of a specialized training course in emergency medicine. ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e13 table 3: general objectives of the field in the studied curriculum country general objectives of the field usa training of graduates who are able to: ï perform diagnostic and therapeutic actions, stabilization, and management of critically ill patients ï quickly identify the problem and refer to appropriate treatment goals ï provide effective pre-hospital care for critically ill or injured patients ï simultaneously treat several patients ï perform executive and educational responsibilities ï use research methods in emergency medicine studies ï create an environment where: ï the highest standards of emergency medical care are training, practice, and monitoring ï focus is on the importance of the social, ethical, behavioral, or organizational aspects of emergency health care ï all personnel of the emergency ward should contribute to the resident training canada objectives: ï by graduating, a resident is expected to rise to the role of an expert to save lives and in the field of basic knowledge of the theory of this expertise, expected to have basic science and research capabilities. ï the emergency medicine specialist uses efficient methods to prioritize, evaluate, intervene, resuscitate, and subsequently manage patients until they are transferred. ï the emergency medicine specialist has organizational skills in emergency management and crisis management and has the necessary ability to deal with the crisis and play a leading role in the formation and organization of medical and pre-hospital emergency services. ï residents must have the knowledge, skills, and attitudes necessary for effective patient-centered care from a wide range of patients. a professional must consider all moral, sexual, cultural, and racial aspects in a professional manner. the emergency medicine specialist has the ability to integrate the above with research, collection, and analysis methods. european union training of emergency medicine specialists australia not mentioned separately saudi arabia training of emergency medicine specialists to meet the needs of the country iran 1) training a sufficient number of specialists to cover all educational and medical centers providing emergency services 2) promoting emergency research through the establishment of emergency research centers and research journals 3) creating subspecialties in emergency medicine such as toxicology, hyperbaric medicine, and . . . 4) the entry of the emergency medical unit into the general curriculum of the doctoral program ifem provide a textbook of curriculum that can train physicians and specialists in emergency medicine who are able to provide the best quality of emergency services in many nations of the world where there are emergency medicine and the establishment of emergency medicine as a specialty worldwide. ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 12 table 4: expected competencies, role, and professional duties of graduates in the studied curriculum country expected capabilities usa capabilities based on principles (acgme) compassionate, appropriate, effective, and timely care for patients with the goal of treating diseases and promoting health having biomedical, clinical, and cognitive knowledge and applying it to inpatient care ability to review and evaluate their performance in the field of patient care, collect and critique scientific documents and compare their performance with those in order to improve patient care having communication and interpersonal skills that lead to the effective exchange of information and teamwork with the patient, his/her family, and other members of the treatment team commitment to professional responsibilities, adherence to ethical principles, sensitivity to a wide range of patients without regard to any discrimination awareness and sense of responsibility towards the health system in the community and the systems of providing medical services and the ability to use the resources of this system properly and effectively to provide optimal patient care. canada capabilities are presented in 7 areas in the field (canmeds( medical specialist colleagues communicator the manager researcher professionalism medical support european union patient care medical knowledge communication, collaboration, and interpersonal skills issues related to professionalism, legal and moral issues organizational planning and administrative management skills education and research australia medical proficiency prioritization and decision-making connections teamwork and collaboration leadership and management scholarship and teaching professionalism saudi arabia capabilities are presented in 7 areas: in the field(canmeds) medical specialist colleague communicator the manager researcher professionalism medical support iran a: capabilities [same as america curriculum capabilities mentioned in table 4] ifem providing comprehensive, immediate care and stabilization of the patient in an emergency, regardless of the emergency situation managing situations that they have to make critical decisions in a short period of time to save the patient’s life giving a possible initial diagnosis and making differential diagnoses and rejecting life-threatening conditions having the knowledge, skills, and attitude determined within the framework of the academic structure and passing all the exams and requirements for obtaining a degree from the relevant university treatment of all patients at any age who present with an acute problem or injury or unexplained physical and behavioral symptoms ability to coordinate and manage simultaneous care of multiple patients, including accidents with multiple casualties determining the need for specialized consultation with other physicians acting as a caregiver, counselor, and patient guide in the acute phase of the disease demonstrating commitment in treating patients in all of the above situations acgme: accreditation council for graduate medical education; ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e13 table 5: the role and professional duties of graduates in the studied curriculum country role and professional duties of graduates usa not defined separately. canada not defined separately. european union not defined separately. australia not defined separately. saudi arabia medical specialist managerial educational cooperation in the medical system iran a in the role of care: evaluation, resuscitation, stabilization, diagnosis, and care of patients referred to the emergency department appropriate follow-up of patients in the emergency department and discharge or referral of patients if necessary performing diagnostic and therapeutic measures related to the field and in accordance with what has been learned b in the educational role: providing training related to patients and their companions, other members of the health team, community population, and academics (if employed at the university as a faculty member) c in the role of research: presenting a research plan, conducting research, analyzing data, and publishing results d in the role of management: management of centers, wards, and emergencies, management of medical teams including trauma team, management of pre-hospital systems and emergency response systems ifem during the training course, a specialist must: have a thorough knowledge of the principles of emergencies and their immediate manifestations and be ready to apply this knowledge in different situations study the necessary knowledge for critical care in the emergency department acquire basic and advanced resuscitation skills, including shock diagnosis and treatment, and practical skills and demonstrate their application in simulated scenarios and real patients be able to differentiate between common acute problems and their treatment in patients with undiagnosed problems, conduct a comprehensive evaluation, analyze clinical findings, and articulate a wide range of differential diagnosis conditions demonstrate complete mastery in cardiopulmonary resuscitation detect airway obstruction and take action recognize all causes of shock at all ages and be able to intervene be able to stabilize the patient by establishing a venous route and prescribing blood and fluids know the principles of brain resuscitation in patients with brain injuries have sufficient skills in using a defibrillator and other cardioversion methods be able to prioritize patients have the ability to interact with other colleagues to solve patient problems have the ability to learn for life be aware of ethical issues related to emergency medicine ifem: international federation for emergency medicine. table 6: educational strategy in the studied curriculum country educational strategy usa not mentioned separately. canada not mentioned separately. european union direct monitoring providing educational opportunities australia not mentioned separately. saudi arabia clinical education basic theory and knowledge training skills training problem-based learning iran an appropriate combination of learner-centered and teacher-centered learning combining basic and clinical sciences systematic approach socialism problem-solving approach ifem providing learning opportunities monitoring and providing feedback in the clinical environment personal learning ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 14 table 7: educational methods and techniques, study method (virtual face-to-face) in the studied curriculum country educational methods and techniques usa seminars skills workshops patient introduction conference journal club group learning patient bedside training other methods according to the possibilities and situations canada morning report grand round review of texts journal club main speeches clinical cases conference skills conferences (procedure) talk about technology diagnostic workshops (ecg) simulation mortality conference (mortality & morbidity) browse the board (board review) european union not listed separately. australia it is not exactly mentioned in the curriculum but emphasizes clinical experience and exposure to the appropriate composition and number of patients. saudi arabia based on the text of the curriculum, the following can be extracted : clinical experience on patients training in small groups virtual teaching using simulators technology review sessions emphasis on distance education for people working in remote areas iran clinical education, educational round training sessions: journal club, magazine review, death conference, book review, ecg review evidence-based lectures simulation workshops (for skills) ifem clinical training in the form of on-site training and educational round training in small groups, including workshops education in large groups including conferences, journal club, mortality conferences virtual training and simulation in the clinical skills training center ifem: international federation for emergency medicine. table 8: conditions and manner of student admission (entry conditions) in the studied curriculum country terms and conditions of student admission usa physicians licensed to work in the united states under u.s. law can apply for the course, and the manager of each residency program will select residents. canada [same as america] european union it is done according to the laws of the european union as well as the national laws of each country. australia it is done according to the laws of australia. physicians who are members of the australian medical system can apply for a specialization course after completing a one-year introductory course in emergency medicine and apply to qualified universities. each university will accept a resident according to its own instructions. saudi arabia the candidate after completing the internship and passing the exam (saudi license exam) can register in the program. people are selected with the opinion of the residency program manager. iran residents are selected by taking the national residency admission exam. ifem being selected by the opinion of the residency program manager. ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e13 table 9: student assessment in the studied curriculum country student evaluation america student evaluations are done as outcome-based. a specific level has been defined for 17 main competencies for each category (in each year). the program manager evaluates the resident in different ways and if they reach this level of capability, the resident can be promoted to a higher year. otherwise, they must acquire that level of capability (milestone project). canada evaluation methods are not discussed separately, but universities have a wide variety of programs for evaluating residents’ clinical knowledge and skills. european union residents should have a portfolio of all their theoretical and clinical activities, and skills. assessment formative: in workplace ï see how patients are cared for ï observing practical activities (procedure) live or video (dops) ï mini clinical examination to check clinical knowledge and skills in doing the procedure as well as their attitudes and how they deal with patients ï casebased discussion, to check clinical reasoning outside the workplace ï including patient presentation, case review, research project, etc. assessment summative: ï periodic written exam ï osce ï check the portfolio australia on-the-job evaluation written test clinical trial (osce) thesis saudi arabia annual upgrade exam midterm exam daily evaluation evaluation of clinical skills master evaluation assessment of residents by each other iran faculty members should regularly evaluate the residents under their supervision. in addition, the residency program must demonstrate that it has an effective mechanism for evaluating the performance of residents throughout the residency period and using the results of this evaluation to improve their performance. the potential use of methods that help inpatient care, theoretical knowledge, communication skills, and professional action should be carefully evaluated. the following tools are recommended: written exams station tests) osce) pmp test dops test key feature problem chart-stimulated recall method 360 degrees logbook review periodic evaluations by faculty members (global rating) b: frequency of evaluation: (periods of assessment) developmental evaluation: should be continuous and periodical and are performed formally at least every three months. final evaluation (compression): residents’ promotion exam is held annually. certificate and encyclopedia exam at the end of the three-year course ifem suggested methods chart-stimulated recall oral examination global rating of performance objective structured clinical examination (osce) procedure or case logs portfolios record review simulations and models oral examination standardized patient (sp) examination clinical patient examination skills written examination dops: direct observation of procedural skills; osce: objective structured clinical examination; ifem: international federation for emergency medicine. table 10: the length of the specialized course of emergency medicine in the studied curriculum country course length usa in most universities, the course is 4 years, but in some centers, the course is 3 years, which is also approved by acep. canada 5 years or family medicine specialty + 1 year european union according to the written curriculum, a period of at least 5 years is suggested. in some countries, emergency medicine is a subspecialty. in some countries, the minimum period is 6-7 years. australia basic training: at least 12 months advanced training: 48 months saudi arabia 4 years iran it is currently 3 years and, in the future, the course will be 4 years. ifem 4 years acep: american college of emergency physicians; ifem: international federation for emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. talebi et al. 16 table 11: number and manner of emergency medicine rotations in the studied curriculum country number and mode of rotation usa american college of emergency physicians (acep) concerning rotations: each university has made changes to the program according to its circumstances emergency department: at least 50% of the course should be in the emergency department anesthesia and intensive care: 2 months surgery and gynecology: there is no specific time. capabilities should be as expected. internal medicine and psychiatry: no specific time is provided. capabilities should be as expected. pediatrics: 4 months or at least 16% emergency work experience prehospital and crisis: required but no specific time is defined. thesis: required but no specific time. canada the canadian association of emergency physicians (caep) on the rotation of each of the universities, changes to the program have been made according to their circumstances. emergency department: 24 months anesthesia and intensive care: 6 months surgical and internal medicine: 8 months, of which at least 1 month is psychiatry. pediatric: 4 months in the pediatric emergency department, of which 2 months should be undertaken as a senior resident. prehospital and crisis: 1 month optional: 12months thesis: prepare a project that is feasible for peer review. for the postgraduate course of family doctor: 6 months emergency and anesthesia, 1-month intensive care, 2 months pediatric, 2 months elective european union there is no specific timeline in the eu curriculum. it is only suggested that the course be at least 5 years and 3 years of it be in the emergency room. here are the rotations related to england. emergency department: 3 years anesthesia and intensive care: 6 months mandatory and 6 months optional. surgical and internal specialties: at least 3 months, the continuation of which is decided depending on the portfolio of each resident and the need for acquiring skills. pediatric: 6 months; resident in pediatric emergency department as a third-year residency. prehospital and crisis: not mandatory but a crisis management course must be taken. optional: not required but can be done off-schedule. thesis: recommended to do an original article. performing a review project in a clinical assignment is required for the graduation exam. australia australasian college for emergency medicine (acem) on the rotation of each of the universities, changes to the program have been made according to their circumstances. emergency department: at least 6 months in conditional education, 30 months in advanced education, at least 12 months in adult emergency. anesthesia and intensive care: in the form of advanced emergency medicine course, minimum 6 months, and maximum 12 months surgery and gynecology specialties: maximum 6 months internal and psychiatric specialties: maximum 6 months pediatrics: in the advanced period, at least 6 months in the pediatric emergency department prehospital and crisis: maximum 6 months elective: a 6-month probationary period in elective or emergency departments. in the advanced course, 18 months in approved sections thesis: a project must be done during the study period. saudi arabia emergency department: adults (23 months), pediatric emergency department (7 months) anesthesia: 2 months intensive care: adults (2 months), pediatrics (2 months) general surgery / trauma: 1 month plastic surgery: 1 month gynecology: 1 month orthopedics: 1 month internal medicine: 1 month cardiology: 1 month neurology: 1 month hajj: 1 month prehospital and crisis: 1 month optional: 3 months thesis: required iran residents in the emergency department must be present for at least 19 months. mandatory rotations first-year internal medicine: 1 month anesthesia: 2 months pediatric: 1 month cardiology: 1 month general surgery: 1 month emergency department: 6 months second-year obstetrics: 1 month toxicology: 2 months orthopedics: 2 months radiology and ultrasound: 1 month ophthalmology: 15 days ent: 15 days emergency department: 5 months third-year pediatric intensive care (critical care): 1 month adult intensive care (critical care): 1 month pre-hospital emergencies: 1 month elective section: 2 months emergency department: 7 months selected parts and maximum time are as follows: internal (1 month), general surgery (1 month), infants (1 month), psychiatry (1 month), ophthalmology (1 month), ear, nose, and throat (1 month), neurology (1 month) the thesis is mandatory (no specific time) ifem the number and selection of rotations are left to the residency program manager. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 41 emergency (2016); 4 (1): 41-44 casr report from pulmonary embolism to inflammatory bowel disease; give tunnel vision up masih tajdini1*, seyed mohammad reza hosseini2 1department of cardiology, tehran heart center, tehran university of medical sciences, tehran, iran. 2department of radiology, massachusetts general hospital, massachusetts, usa. *corresponding author: masih tajdini; department of cardiology, tehran heart center, tehran university of medical sciences, tehran, iran. tel: 00989125645406 e-mail: drmasih84@yahoo.com received: june 2015; accepted: june 2015 abstract inflammatory bowel disease (ibd) is a multisystem disorder with gastrointestinal tract involvement. these patients have the higher risk for thromboembolic events compared to normal population. this report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease. key words: inflammatory bowel disease; pulmonary embolism; venous thrombosis cite this article as: tajdini m, hosseini smr. from pulmonary embolism to inflammatory bowel disease; give tunnel vision up. emergency. 2016;4(1):41-44. introduction: nflammatory bowel disease (ibd) is a multisystem disorder with gastrointestinal tract involvement. this disease is usually characterized by specific features like chronic or nocturnal diarrhea, abdominal pain, weight loss, fever and rectal bleeding. this disease can correlate with systemic and extra-intestinal complications (1). elevated thrombin–antithrombin complexes, prothrombin fragments, and d-dimer levels and their increases with disease activity are other evidence pointing toward the relation between inflammation and coagulation. these factors lead to higher risk of thromboembolic events in ibd patients compared to normal population (2-4). the incidence of systemic thromboembolic events in ibd ranges from 1%– 7.7% and 39%–41% in clinical and postmortem studies, respectively. similar to other patients, deep vein thrombosis (dvt) and/or pulmonary thromboembolism (pte) are the most common thrombotic events. cerebral, portal, mesenteric, and retinal veins thrombosis have fewer occurrences (5). these events are associated with increased risk of mortality and require improved awareness and prevention (6). this report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease. case report: a 46-year-old female was referred to t department with pain and edema of her right leg. she was a known case of hypertension and hyperlipidemia and had a history of left leg dvt about two years ago. in previous admission she was discharged on warfarin but after few months of treatment, warfarin had been stopped due to active peptic ulcer disease. collagen vascular markers such as antinuclear antibody (ana), anti-double stranded dna (anti-dsdna), anticardiolipin and lupus anticoagulant antibodies were negative in first admission which were requested due to recurrent abortions (three times) in her past medical history. doppler ultrasound was performed to evaluate her leg pain and edema. findings revealed popliteal and superficial femoral vein thrombosis. i figure 1: chest computed tomography angiography of patient, arrow pointed the location of embolus in the right main pulmonary artery. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com tajdini et al 42 she was admitted again and anticoagulant therapy was started. during her admission, dyspnea was developed; so pulmonary computed tomography angiography (cta) was performed and pulmonary emboli was demonstrated (figure 1). in addition to dyspnea she was complaining of abdominal pain and non-bloody diarrhea. thrombosis of intra-abdominal vessels was ruled out with magnetic resonance venography (mrv). since her abdominal pain was resistant to analgesics and she had a past surgical history of appendectomy, abdominal ct scan was performed which showed sub-mucosal bleeding and thickness of jejunum indicating probable ibd diagnosis. the patient underwent colonoscopy due to abdominal pain, past medical history, intermittent non-bloody diarrhea, and abdominal ct findings. unexpectedly, patchy ulceration was seen coincident of ibd (figure 2). the patient was treated by intravenous unfractionated heparin and discharged on warfarin. follow up in out-patient clinic for international normalized ratio (inr) level monitoring (target between 2 and 3) was arranged. discussion: venous thromboembolism incidence differs from 1.3% to 6.2 % and has a mortality rate of 8% to 25% in ibd population. most of thromboembolic events occur in ibd patients who are younger than 50 and is more common in females compared to males (7). like ibd pathogenesis, the mechanism of hypercoagulability state is not fully understood. despite the role of inflammation in activation of coagulation cascade, it seems that this higher incidence rate of thrombosis in ibd is not linked to inflammatory process and evidence in literature has been considered ibd as an independent risk factor for thromboembolism (table 1) (8, 9). some studies have implicated platelet activation by endothelial dysfunction and hyperhomocysteinemia activation of the coagulation cascade (10). inherited causes of thrombophilia such as factor v leiden mutation, prothrombin gene mutation, inherited hyperhomocysteinemia, mthfr gene polymorphism, deficiency of protein c and s, antithrombin iii mutation does not associate with thrombotic events in patients with ibd. for patients who are diagnosed with venous thromboembolism (vte), work-up is often necessary to indicate the underlying cause. the first diagnostic steps are rectal examination, fecal occult blood testing and colonoscopy to rule out malignancy which is a strong risk factor for vte. in absence of inherited causes, acquired one may play a crucial role, but all of them including prolonged immobilization, surgery, fluid depletion, steroid therapy, central venous catheters, smoking and oral contraceptive were absent in our patient (4, 11-13). bleeding tendency makes the treatment of these patients so difficult. heparin has been implicated in the therapeutic management of ulcerative colitis with thromboembolism. two studies showed controversial role for heparin. one of them revealed benefits of use but another failed to repeat this finding and was associated with increased risk of bleeding. evidence is not enough to utilize low molecular weight heparin. thrombolytic agents can be life saver in ibd patient with massive pte. cardiogenic shock and/or right ventricular dysfunction are the main indication of administration. vitamin k antagonists should be used with caution due to risk of causing large hemorrhage. considering above; management of these patients needs multi specialist consultation (14). based on new consensus, testing for hereditary or acquired hypercoagulability states is not necessary in ibd patients with vte. in the absence of another provoking factor in clinical remission state of ibd, anticoagulant therapy at least for 3 months has been recommended with periodic reevaluation. there is no recommended follow up time for these patients but based on new consensus echocardiography and cta can be repeated for reevaluation of anti-coagulation therapy. it seems that persistent use of anticoagulant is not obligatory in patients with good right ventricular function or no evidence of pte in mentioned investigations (15). however, there is no difference between the management of an acute thrombotic event in patients with ibd and other patients. patients with diagnosis of pte need electrocardiography and echocardiography evaluation. in patients with massive saddle emboli, evidence of right heart strain or hypertension is an independent predictor of mortality. hence, thrombolysis should be considered. currently, there is no preferred medication and low-molecular-weight heparin (lmwh) or un-fractionated heparin (ufh) have equal effects (16). conclusion: inflammation and coagulation have been implicated in the pathogenesis of numerous diseases like ibd. imbalance between prothrombotic and protective mechanisms leads to thrombosis and pathologic blood coagulation. therefore, finding and treatment of probable underline causes of thrombosis should be considered in all vte patients referred to the emergency department. figure 2: colonoscopy views of patient’s sigmoid (left) and rectum (right), arrow pointed to location of patchy ulceration compatible with inflammatory bowel disease. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 43 emergency (2016); 4 (1): 41-44 acknowledgment we would like to express our special thanks to the cardiology department staff of tehran heart center, tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. tajdini m, mirbagheri sa, nikooie r, et al. tissue hypoxia in pathogenesis of ulcerative colitis: should we change all our beliefs? scand j gastroenterol. 2013;48(12):1487-8. 2. souto jc, martínez e, roca m, et al. prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. dig dis sci. 1995;40(9):1883-9. 3. smith c, haire w, kaufman s, mack d. determination of prothrombin activation fragments in young patients with inflammatory bowel disease. am j gastroenterol. 1996;91(6):1221-5. 4. baratloo a, safari s, rouhipour a, et al. the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis. emergency. 2014;2(1):1-11. 5. kasmaei hd, baratloo a, nasiri z, soleymani m, shirafkan a, hamedi zs. report of nineteen cerebral vein thrombosis referrals to an emergency department: a case series and literature review. arch neurosci. 2015;2(2). 6. temel t, ozakyol a, korkmaz h. inflammatory bowel disease with thromboembolic complications. int j mevlana med sci. 2014;2(1):5-6. 7. choi sk, kasturi l, tavakoly a, safier hl. ulcerative colitis diagnosed in a patient with venous thromboembolism. hosp physician. 2008:33. 8. talbot rw, heppell j, dozois rr, beart rw, editors. vascular complications of inflammatory bowel disease. mayo clin proc; 1986: elsevier. 9. zitomersky nl, verhave m, trenor cc. thrombosis and inflammatory bowel disease: a call for improved awareness and prevention. inflamm bowel dis. 2011;17(1):458-70. 10. novacek g, miehsler w, kapiotis s, katzenschlager r, speiser w, vogelsang h. thromboembolism and resistance to activated protein c in patients with inflammatory bowel disease. am j gastroenterol. 1999;94(3):685-90. 11. oldenburg b, van tuyl ba, van der griend r, fijnheer r, van berge henegouwen gp. risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia. dig dis sci. 2005;50(2):235-40. 12. twig g, zandman‐goddard g, szyper‐kravitz m, shoenfeld y. systemic thromboembolism in inflammatory bowel disease: table 1: review of the literature (ibd and thrombotic events) authors publication date major presentation wlodarczyk et al. (17) 2014 in this paper authors report three cases of vte in ibd patients. temel et al. (6) 2013 two case of pulmonary thromboembolism active inflammatory bowel disease patients. merrill and millham (18) 2012 patients with ibd are at increased risk for developing postoperative dvt or pe. o'connor et al. (19) 2009 case of a patient with ulcerative colitis who has had recurrent thromboembolism. choi et al. (7) 2008 case of a man who was hospitalized with massive pe and deep vein thromboembolism and subsequently was diagnosed with underlying ulcerative colitis. kafkas et al. (14) 2008 massive pe in a patient with ulcerative colitis. jin et al. (20) 2005 exacerbation of ulcerative colitis and developed extensive arterial and venous thrombosis. katsanos et al. (21) 2005 patients with cvt and ibd were significantly younger than cvt patients without ibd (review and analysis of 65 case reports of ibd patients with cvt). solem et al. (22) 2004 venous thromboembolism is a serious complication of ibd. bernstein et al. (23) 2001 ibd patients have a threefold increased risk of developing dvt or pe. ibd: inflammatory bowel disease; vte: venous thromboembolism; dvt: deep vein thrombosis; pe: pulmonary embolism; cvt: cerebral vein thrombosis. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com tajdini et al 44 mechanisms and clinical applications. ann n y acad sci. 2005;1051(1):166-73. 13. kasmaei hd, baratloo a, soleymani m. a 33-year-old woman with severe postpartum headache. emergency. 2013;1(1):27-9. 14. kafkas nv, deboneras cc, babalis dk. massive pulmonary embolism and ulcerative colitis. hellenic j cardiol. 2008;49(5):365-70. 15. nguyen gc, bernstein cn, bitton a, et al. consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: canadian association of gastroenterology. gastroenterology. 2014;146(3):835-48. e6. 16. büller hr, agnelli g, hull rd, hyers tm, prins mh, raskob ge. antithrombotic therapy for venous thromboembolic disease: the seventh accp conference on antithrombotic and thrombolytic therapy. chest. 2004;126(3_suppl):401s-28s. 17. wlodarczyk m, sobolewska a, fichna j, wisniewskajarosinska m. prevention and therapeutic strategies of thromboembolic events in patients with inflammatory bowel diseases: a report of three cases. curr drug targets. 2015;16(3):194-8. 18. merrill a, millham f. increased risk of postoperative deep vein thrombosis and pulmonary embolism in patients with inflammatory bowel disease: a study of national surgical quality improvement program patients. arch surg. 2012;147(2):120-4. 19. o'connor mb, o'donovan n, phelan mj, regan mj. inflammatory bowel disease, such as ulcerative colitis, is a risk factor for recurrent thromboembolic events: a case report. cases j. 2009;2(1):173. 20. jain s, bhatt p, muralikrishna gk, malhotra p, kumari s, varma s. extensive arterial and venous thrombosis in a patient with ulcerative colitis--a case report. med gen med. 2005;7(2):10. 21. katsanos ah, katsanos kh, kosmidou m, giannopoulos s, kyritsis ap, tsianos ev. cerebral sinus venous thrombosis in inflammatory bowel diseases. qjm. 2013;106(5):401-13. 22. solem ca, loftus ev, tremaine wj, sandborn wj. venous thromboembolism in inflammatory bowel disease. am j gastroenterol. 2004;99(1):97-101. 23. bernstein cn, blanchard jf, houston ds, wajda a. the incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. thromb haemost. 2001;85(3):430-4. archives of academic emergency medicine. 2023; 11(1): e6 or i g i n a l re s e a rc h the effect of intravenous metoclopramide on gastric emptying of opium-dependent patients based on ultrasonographic criteria; a case-control study faramarz mosaffa1, ali arhami dolatabadi2, masoomeh raoufi3, faezeh golpour4, mahshid ghasemi1, mohammad javad yazdipoor2, elham memary5,6∗ 1. anesthesiology department, akhtar hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. radiology department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 4. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 5. anesthesiology research center, ayatollah taleghani hospital, shahid beheshti university of medical sciences, tehran, iran. 6. anesthesiology department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: induction of anesthesia for emergency procedures, without prior gastric preparation and incomplete fasting, is associated with the risk of reflux of stomach contents and aspiration. this study aimed to evaluate the effect of intravenous (iv ) metoclopramide administration on gastric emptying in opium users, candidate for procedural sedation and analgesia (psa). methods: in the present case-control study, opium-dependent (case) and non-dependent (control) patients in need of psa were administered with 10 mg iv metoclopramide after undergoing gastric ultrasonography for determination of its area and contents. then, 30 minutes after the administration of metoclopramide, the area and contents of the stomach were measured again and compared with the measures obtained before the intervention. results: 135 patients were evaluated in three groups of 45, including the case, control, and placebo groups. the three groups were similar regarding mean age (p = 0.068), sex (p = 0.067), weight (p = 0.596), height (p = 0.671), body mass index (bmi) (p = 0.877), duration of fasting (p = 0.596), and type of gastric contents (p = 0.124). mean antral cross-sectional area (csa) of the study participants in the case, control, and placebo groups before the administration of the drug was 8.49 ± 1.40, 8.31 ± 2.56, and 6.56 ± 1.72 cm2, respectively. mean gastric area in the case (p < 0.001) and control (p < 0.001) groups had significantly decreased after the intervention. mean antral gastric grade of gastric contents in the case (p < 0.001) and control (p < 0.001) groups had significantly decreased after the intervention. conclusion: it seems that metoclopramide administration in opium users in need of psa leads to a significant decrease in mean gastric area and increases gastric emptying. keywords: deep sedation; emergency treatment; anesthesia; respiratory aspiration; ultrasonography; clinical trial cite this article as: mosaffa f, arhami dolatabadi a, raoufi m, golpour f, ghasemi m, yazdipoor mj, memary e. the effect of intravenous metoclopramide on gastric emptying of opium-dependent patients based on ultrasonographic criteria; a case-control study. arch acad emerg med. 2023; 11(1): e6. https://doi.org/10.22037/aaem.v11i1.1892. ∗corresponding author: elham memary; anesthesiology research center, ayatollah taleghani hospital, velenjak, shahid arabi street, tehran, iran. email: drmemary@gmail.com, tel: 00989122847642, orcid: https://orcid.org/0000-0002-4845-9342. 1. introduction incomplete fasting at the time of anesthesia induction or administration of sedative-hypnotic drugs, which are associated with loss of protective reflexes such as cough and swallowing, is associated with the risk of reflux of stomach contents and aspiration. therefore, in contrast to candidate patients for elective surgery, in emergency situations, when delaying the intended procedure or surgery for increasing fastthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index f. mosaffa et al. 2 ing time is not possible, there is a higher risk of pulmonary aspiration (1-3). considering that this event is a very serious and dangerous side effect of anesthesia induction and can be associated with substantial morbidity and mortality, taking proper measures for its prevention is essential (4, 5). conditions such as pregnancy, drug abuse, diabetes, and renal failure, which are associated with decrease in gastric movement, as well as conditions leading to increase in intraabdominal pressure, including obesity, ascites, and abdominal tumors are among known risk factors for aspiration during anesthesia induction. gastric volume and acidity of its contents are among other factors that are known to increase the probability of aspiration and its severity and many interventions have been tested with the aim of affecting these variables (5). various medications, like antacids, prokinetics, antiemetics, and anticholinergics or a combination of them have been used for decreasing the risk of aspiration before induction of anesthesia in emergency situations. additionally, measures such as inserting nasogastric (ng) tube, and gastric emptying, placing the head in a downward 1520° angle and sellick maneuver are among the non-drug interventions used in this regard (6). to evaluate the efficacy of these interventions various methods have been introduced. in recent years, ultrasonography has been used for qualitative and quantitative evaluation of gastric contents as well as assessing the effect of different interventions, some of which were mentioned (7). the effect of prescribing metoclopramide on gastric motility based on ultrasonographic criteria has been evaluated in different studies (7-11). however, its efficiency in patients with drug abuse has rarely been assessed. meanwhile, considering the effect of drugs on gastrointestinal tract movements, there is more concern regarding decrease in gastrointestinal tract movements and lowered response to prescription of prokinetic drugs, including metoclopramide, in these patients (12-14). considering the afore-mentioned points, the present study was designed and performed with the aim of evaluating the effect of iv metoclopramide on gastric emptying in patients with drug abuse, who were candidates for undergoing procedural sedation and analgesia (psa). 2. methods 2.1. study design and settings the present case-control study was performed on opiumdependent (case) and non-dependent (control) patients in need of psa in the emergency department of imam hossein hospital, tehran, iran, between 2021 and 2022. after undergoing gastric ultrasonography for determination of its area and contents, the patients were divided into 3 groups of case (opium-dependent patients who received 10 mg iv metoclopramide), control (non-opium-dependent patients who received 10 mg iv metoclopramide) and placebo (non-opiumdependent patients who received 2cc distilled water). then, 30 minutes later, the area and quality of gastric contents were measured and compared with measures before the intervention. the proposal of this study was approved by the ethics committee of shahid beheshti university of medical sciences (ir.sbmu.msp.rec.1399.154). in addition, the protocol of this study was registered on the iranian registry of clinical trials under the code irct20210406050864n1. after providing explanations regarding the protocol of the study, informed written consent was obtained from the patients for participation in the present study. no additional costs were inflicted on the patients or the health care system as a result of this study and the researchers adhered to the confidentiality of patients’ data and ethical principles in biomedical research based on the declaration of helsinki. 2.2. study population the study population consisted of patients with a history of daily drug abuse for more than 6 weeks, using any type of opioid (derivatives of poppies or opium), who were candidates for psa and had eaten solid food less than 8 hours before or drank liquids less than 2 hours before. patients who were unable to assume the proper position for ultrasonography, those with body mass index (bmi) over 35, obstruction in the gastrointestinal tract, diabetes, history of gastric surgery, hiatal hernia, those who had used medications that change gastrointestinal tract movements in the previous 72 hours, and those with history of allergic or extrapyramidal reactions after receiving metoclopramide were excluded from the study. the control and placebo groups were selected from non-dependent individuals with a similar situation. 2.3. intervention all of the patients included in the study were under full cardiopulmonary monitoring and their vital signs were recorded. then the patients were divided into 3 groups of case, control, and placebo. all the patients underwent ultrasonography by a radiologist in supine and right lateral positions and their gastric area and its contents’ qualities were evaluated and registered. the control group included non-dependent individuals and the case group included dependent patients, all of whom received 10 mg (2cc) iv metoclopramide. the placebo group consisted of non-dependent patients who received 2cc distilled water instead of metoclopramide. the onset of action of iv metoclopramide is 1-3 minutes and it reaches the peak of action in 15-20 minutes. therefore, the second measurement was done 30 minutes after the prescription of the drug or placebo. the person prescribing the drug was aware of the groupings, but the patients and the radiologist in charge of performing the ultrasonography were blind to the groupings. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 3 archives of academic emergency medicine. 2023; 11(1): e6 table 1: comparing the baseline characteristics of participants between the three study groups variable placebo (n = 45) control (n = 45) case (n = 45) p-value age (year) mean ± sd 50.8 ± 15.9 43.1 ± 18.0 49.3 ±15.8 0.068 sex male 25 (55.6) 16 (35.6) 26 (57.8) 0.067 female 20 (44.4) 29 (64.4) 19 (42.2) weight (kg) mean ± sd 69.5 ± 14.7 66.7 ± 9.3 67.2 ±14.5 0.596 height (m) mean ± sd 1.7 ± 0.05 1.6 ± 0.07 1.7 ± 0.04 0.671 bmi mean ± sd 23.7 ± 3.9 24.3 ± 4.4 23.9 ± 3.8 0.877 fasting time (hour) mean ± sd 3.3 ± 1.4 3.6 ± 2.1 3.6 ± 1.4 0.596 type of food consumed liquid 32 (71.1) 39 (86.6) 36 (80.0) 0.124 solid 13 (28.9) 6 (13.4) 9 (20.0) data are presented as mean ± standard deviation (sd) or frequency (%). bmi: body mass index. the control group included nonopium dependent individuals and the case group included opium dependent patients, all of whom received 10 mg (2cc) iv metoclopramide. the placebo group consisted of nonopium dependent patients who received 2cc distilled water instead of metoclopramide. table 2: comparing gastric ultrasonography findings in the three study groups before and after the intervention group before intervention after intervention p-value antral cross-sectional area (cm2 ) case 8.49 ± 4.34 4.34 ± 1.52 < 0.001 control 8.31 ± 2.56 4.44 ± 1.37 < 0.001 placebo 6.59 ± 1.72 6.34 ± 1.92 0.140 antral gastric grade case 1.56 ± 0.50 0.76 ± 0.68 < 0.001 control 1.60 ± 0.49 0.87 ± 0.66 < 0.001 placebo 1.42 ± 0.50 1.33 ± 0.94 0.486 data are presented as mean ± standard deviation (sd). figure 1: measuring mean antral cross-sectional area (csa) using ultrasonography in supine and right lateral positions. 2.4. ultrasonographic evaluation patients in all three groups underwent ultrasonography in supine and right lateral positions by a radiologist. mean antral cross-sectional area (csa) was measured and antral gastric grade (agg) was also evaluated. mean antral cross-sectional area (csa) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index f. mosaffa et al. 4 figure 2: evaluating antral gastric grade (agg) using gastric ultrasonography findings. table 3: changes in antral gastric grade (agg) of patients after the intervention based on group variable placebo (n = 45) control (n = 45) case (n = 45) p value 1 grade increase 11 (24.4) 2 (4.4) 1 (2.2) no change 22 (48.9) 15 (33.3) 14 (31.1) < 0.001 1 grade decrease 9 (20.0) 21 (46.6) 23 (51.1) 2 grades decrease 3 (6.7) 7 (15.6) 7 (15.6) data are presented as frequency (%). the control group included nonopium dependent individuals and the case group included opium dependent patients, all of whom received 10 mg (2cc) iv metoclopramide. the placebo group consisted of nonopium dependent patients who received 2cc distilled water instead of metoclopramide. in all patients, csa was determined by an experienced radiologist using sonosite2 device and rc60xi 2-5 mhz probe in supine and right lateral positions and in sagittal view of antrum, based on anatomical landmarks of the stomach. csa and antral volume were calculated. measurement of csa was done using measures of vertical thickness in longitudinal d1 and posterior d2 planes in centimeters and from the serosa of one side to the serosa of the other side. for measuring the cross-section of the antrum, the following formula was used: [csa = 3.14 (d1×d2) ×0.4]. based on previous studies, the cut-off for determining the volume of the stomach was considered to be > 1.5cc, and for determining the presence of solid or liquid contents, it was considered to be 3.01 cm2 (figure 1). evaluating antral gastric grade (agg) qualitative evaluations of agg for determining the presence or absence of solid and liquid contents were performed in 3 grades (0, 1, 2) as follows (figure 2): grade 0: absence of contents; grade 1: presence of evidence of contents only in right lateral position; and grade 2: presence of evidence of contents in both supine and right lateral positions. the mathematical model used for calculating the volume of contents and determining antral volume in this study was: volume=27+(14.6*rl csa)-(1.28*age) 2.5. statistical analysis based on the study by sayyadi et al. (8), the number of samples in each group was determined to be 45 and sampling was continued until reaching the intended sample size in all 3 groups. to analyze the data, spss software version 26 was used and findings were reported as mean ± standard deviation or frequency (%). to evaluate the normality of data, kolmogorov–smirnov test was applied. to compare the quantitative variables in the 2 groups, independent samples t-test or one-way analysis of variance, and for categorized variables, chi square and fisher’s exact test, and for normal quantitative variables in each group (before and after intervention), dependent t-test or paired t-test was used. to compare the gradings of the patient’s stomach before and after the intervention, mantel–haenszel test was applied. in all tests, the significance level was considered to be less than 0.05. 3. results 3.1. baseline characteristics of the studied patients in this study, 135 patients were studied in 3 groups of 45 including case, control, and placebo groups. the baseline characteristics of the patients has been compared between the 3 study groups in table 1. the 3 groups were similar regarding mean age (p = 0.068), sex (p = 0.067), weight (p = 0.596), height (p = 0.671), body mass index (bmi) (p = 0.877), duration of fasting (p = 0.596), and type of food consumed instead of type of gastric content (p = 0.124). the participants in the case group were opiumdependent, and would usually use it once a day, and most of them had a history of using opium for more than 7 years; their most common route of consumption was the oral route. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 5 archives of academic emergency medicine. 2023; 11(1): e6 3.2. ultrasonographic findings mean csa mean csa of the patients participating in the study in case, control, and placebo groups before the administration of the drug was 8.49 ± 1.40, 8.31 ± 2.56, and 6.56 ± 1.72 cm2, respectively. table 2 compares the mean csa before and after the administration of the drug in the 3 studied groups. in contrast to the placebo group, mean csa had significantly decreased in the case (p < 0.001) and control (p < 0.001) groups after the intervention. mean csa of the patients after the administration of the drug in the case group was lower that the control group, and in the control group it was less than the placebo group (p < 0.001). evaluating agg table 2 compares the mean qualitative score of gastric contents in the 3 studied groups before and after the intervention. in contrast to the placebo group, mean agg had significantly decreased in the case (p < 0.001) and control (p < 0.001) groups after the intervention. mean agg of the patients after the administration of the drug in the case group was lower that the control group, and in the control group it was less than the placebo group (p < 0.001). table 3 compares aggs of the 3 studied groups after the intervention. 4. discussion based on the results of the present study and considering the ultrasonographic findings, it seems that prescription of metoclopramide in opium users in need of psa can significantly decrease mean csa and increase gastric emptying. the effect of metoclopramide on acceleration of gastric emptying and decreasing gastric volume in patients in need of psa, who have not had enough fasting time, has been confirmed in previous studies using different measuring methods, including use of ultrasonographic indices. yet, the effectiveness of this intervention in opium users has been a matter of question. most opiate agonists, including morphine, lead to less motility in the gastrointestinal tract through stimulation of mu receptors. decrease in gastric motility, increase in tonicity of the sphincter, change in motility patterns, and peristaltism are commonly seen following use of opiates. in fact, these compounds lead to increase in contraction of gastric antrum and pylorus and the upper parts of the duodenum, as well as decrease in tonicity in the relaxed state of the gastric muscles (12-14). on the other hand, metoclopramide is an antagonist of d2 receptor, which can inhibit the effects of the endogenous dopamine transmitter on the gastrointestinal tract. endogenous dopamine leads to decreased motility of the stomach and proximal small intestine by inhibiting the release of acetylcholine, and its effects are neutralized with the injection of metoclopramide (15). in a study by sayyadi et al., qualitative and quantitative ultrasonographic evaluation of the stomach before surgery was done in candidate patients in need of emergency surgery, who received 10 mg metoclopramide. in that study, drugdependent patients and those using opiates were excluded from the study. the results of that study showed that although agg and csa of the 2 groups were not significantly different after intervention, mean decrease in csa in the metoclopramide group was higher than the control group, and the decrease observed in agg after the intervention in the metoclopramide group was higher than the control group (8). comparing the results of the present study with that study can lead to the hypothesis that metoclopramide has even higher effectiveness in opium users; as in the present study, those in the case group showed a significant decrease in csa and agg compared to control and placebo groups. in the systematic review by priya vijayvargiya et al. performed in 2019, there were 899 included articles, in 22 of which gastric emptying (ge) was studied, in 23 studies upper gastrointestinal tract symptoms (ugi sx), and in 14 studies both ge and ugi sx were evaluated. in 18 of the studies the effects of d2 receptor antagonists, including metoclopramide and domperidone, on both ugi sx and ge were evaluated. in 6 studies, these medications were associated with 20 to 50% improvement in ge, in 4 studies no difference was found in ge, in 13 studies there was 20 to 50% improvement in ugi sx, and in 2 studies no difference was found in ugi sx. of course, in these studies the patients were mainly divided into 2 groups of patients with gastroparesis (gp) and functional dyspepsia (fd), both of which showed similar improvement in ge. the study also showed that there was a significant correlation between improvement in ge and changes related to ugi sx. in that study, opioid users were not evaluated and analyzed, and thus, in the conclusion of the study, it was suggested to perform further studies in similar populations using optimal tests and more proper evaluations for ge and ugi sx (16). it seems that considering the risk of aspiration of gastric contents in emergency procedures without gastric preparation, using medications such as metoclopramide, which accelerate ge, can help reduce the probability of this event. 5. limitation the 3 studied groups were not homogenous regarding ultrasonographic indices before the intervention. additionally, considering the absence of aspiration in all of the groups following induction of anesthesia, nothing can be said regarding the effect of this medication on the prevalence of aspiration. also, there is the possibility of wrong and inaccurate self-declaration of opium users regarding the type of subthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index f. mosaffa et al. 6 stance used and the last time using it and even the duration of fasting. of course, we tried to minimize its probability by fully explaining the importance of receiving correct information. 6. conclusion it seems that metoclopramide administration in opium users in need of sedation for emergency procedures leads to significant decrease in acs and increase in gastric emptying. 7. declarations 7.1. acknowledgments not applicable. 7.2. conflict of interest there is not to declare. 7.3. funding and supports this study has been funded and supported by the iran university of medical sciences (iums); [grant no: 1400-1-3220043.] 7.4. authors’ contribution study design: aad, ss; data gathering: sjy, mr, em; analysis: ss; interpretation of results: ss, aad, sjy, mr; drafting: ss, sjy; critically revised: all authors. references 1. kluger m, short t. aspiration during anaesthesia: a review of 133 cases from the australian anaesthetic incident monitoring study (aims). anaesthesia. 1999;54(1):19-26. 2. kluger mt, culwick md, moore mr, merry af. aspiration during anaesthesia in the first 4000 incidents reported to webairs. anaesthesia and intensive care. 2019;47(5):442-51. 3. cook t. strategies for the prevention of airway complications–a narrative review. anaesthesia. 2018;73(1):93-111. 4. hewson dw, moppett i. preoperative fasting and prevention of pulmonary aspiration in adults: research feast, quality improvement famine. british journal of anaesthesia. 2020;124(4):361-3. 5. nason ks. acute intraoperative pulmonary aspiration. thoracic surgery clinics. 2015;25(3):301. 6. robinson m, davidson a. aspiration under anaesthesia: risk assessment and decision-making. continuing education in anaesthesia critical care & pain. 2014;14(4):171-5. 7. perlas a, mitsakakis n, liu l, cino m, haldipur n, davis l, et al. validation of a mathematical model for ultrasound assessment of gastric volume by gastroscopic examination. anesthesia & analgesia. 2013;116(2):357-63. 8. sayyadi s, raoufi m, dolatabadi aa, rostami m, memary e. ultrasonographic assessment of metoclopramide administration effectiveness in accelerating gastric emptying before urgent surgery in patients with insufficient npo time. anesthesiology and pain medicine. 2020;10(5). 9. abdolrazaghnejad a, banaie m, safdari m. ultrasonography in emergency department; a diagnostic tool for better examination and decision-making. advanced journal of emergency medicine. 2018;2(1). 10. nasr-esfahani m, behravan m, esmailian m. the correlation between ultrasonographic gastric antral area and vomiting in patients undergoing procedural sedation and analgesia. frontiers in emergency medicine. 2020;4(4):e83-e. 11. bouvet l, chassard d. ultrasound assessment of gastric contents in emergency patients examined in the full supine position: an appropriate composite ultrasound grading scale can finally be proposed. springer; 2020. p. 865-8. 12. mahmoud reza k, masour reza s, farhad z. < the> usage of opioids and their adverse effects in gastrointestinal practice: a review. 2013. 13. brock c, olesen ss, olesen ae, frøkjaer jb, andresen t, drewes am. opioid-induced bowel dysfunction. drugs. 2012;72(14):1847-65. 14. farmer ad, drewes am, chiarioni g, de giorgio r, o’brien t, morlion b, et al. pathophysiology and management of opioid-induced constipation: european expert consensus statement. united european gastroenterology journal. 2019;7(1):7-20. 15. camilleri m, atieh j. new developments in prokinetic therapy for gastric motility disorders. frontiers in pharmacology. 2021:2216. 16. vijayvargiya p, camilleri m, chedid v, mandawat a, erwin pj, murad mh. effects of promotility agents on gastric emptying and symptoms: a systematic review and metaanalysis. gastroenterology. 2019;156(6):1650-60. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e55 rev i ew art i c l e prevalence of compartment syndrome and disseminated intravascular coagulation following rhabdomyolysis; a systematic review and meta-analysis bardia danaei1, ali sharifi2∗, hamid mazloom3, iraj najafi4, mehri farhang ranjbar5, saeed safari5,1 † 1. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 2. assistant professor of hepatopancreaticobiliary & organ transplantation surgery, school of medicine, tabriz university of medical sciences, tabriz, iran. 3. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. nephrology department, shariati hospital, tehran university of medical sciences, tehran, iran. 5. research center for trauma in police operations, directorate of health, rescue & treatment, police headquarter, tehran, iran. received: june 2023; accepted: july 2023; published online: 1 august 2023 abstract: introduction: rhabdomyolysis (rm) may cause some complications such as compartment syndrome and disseminated intravascular coagulation (dic), which can affect its prognosis. this systematic review and meta-analysis aimed to investigate the prevalence of the mentioned complications following rm. methods: medline, embase, and scopus databases were searched using keywords related to compartment syndrome, dic, and rhabdomyolysis with appropriate combination. cohort and cross-sectional studies that conducted research on the prevalence of compartment syndrome and dic in patients with rm were included in the present study. the desired data were extracted from the included studies and meta-analysis was conducted on them to calculate pooled prevalence of these complications. results: twenty articles were included in our systematic review. the rate of compartment syndrome reported in these studies ranged from 0 to 30.7%. our meta-analysis revealed the pooled prevalence of 4% (95% confidence interval (ci): 2.20 to 7.40) for compartment syndrome in these studies. the pooled prevalence of this complication was 7.1% (95% ci: 2.90 to 16.00) among patients with severe rm and 4.4% (95% ci: 1.80 to 10.00) in traumatic rm. the rate of dic reported in the included studies ranged from 0 to 40.47%. our meta-analysis showed the pooled prevalence of 8.3% (95% ci: 03.90 to 16.50) for this complication among rm patients. conclusion: we reported the rates of compartment syndrome and dic in rm patients based on rhabdomyolysis etiologies through an epidemiologic systematic review and meta-analysis. the rate of compartment syndrome was slightly higher in patients with severe rm and its rate in patients with traumatic rm was close to the overall rate of compartment syndrome. keywords: rhabdomyolysis; compartment syndromes; disseminated intravascular coagulation; systematic review cite this article as: danaei b, sharifi a, mazloom h, fazli f, najafi i, farhang ranjbar m, safari s. prevalence of compartment syndrome and disseminated intravascular coagulation following rhabdomyolysis; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e55. https://doi.org/10.22037/aaem.v11i1.2083. ∗corresponding author: ali sharifi; hepatopancreaticobiliary & organ transplantation surgery, school of medicine, tabriz university of medical sciences, tabriz, iran. email: sharifi331@yahoo.com, orcid: https://orcid.org/0000002-4179-202x. † corresponding author: saeed safari; men’s health and reproductive health research center, shohadaye tajrish hospital, tajrish square, tehran, iran. email: safari266@gmail.com, tel: 009822721155, orcid: https://orcid.org/0000-0002-7407-1739. 1. introduction rhabdomyolysis (rm) is a clinical condition characterized by a loss of muscle strength, muscle pain, and swelling. this condition is associated with a creatine kinase (ck) level exceeding 1000 iu/l or ck being more than five times the upper limit of normal (uln) for a mild form of rm as per standard definition. if myoglobinuria and acute kidney injury (aki) are present, it indicates a severe form of rm (1). the development of rhabdomyolysis is caused by an elevation of ionized calcium levels within the cytoplasm, which contributes to its pathogenesis. in theory, rhabdomyolysis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. danaei et al. 2 can be triggered by various forms of muscle damage and any factors that result in or contribute to muscle damage (2). among adults, the existing data indicate that the most frequent causes of rhabdomyolysis are drug or alcohol abuse, use of certain medications, traumatic injuries, neuroleptic malignant syndrome (nms), and prolonged periods of immobility (3). rm may cause some complications, which can affect its prognosis (4). the most important one is aki, for which research indicated a wide range prevalence of 15% to over 50% in rm patients (3, 5, 6). however, besides aki there are other complications that need to be noticed by clinicians; including compartment syndrome, disseminated intravascular coagulation (dic), and electrolyte imbalance (7). the release of muscle cells’ content can cause local edema, which remains trapped within fascia and can lead to compartment syndrome (8). compartment syndrome occurs when elevated pressure within a closed anatomical space poses a threat to the viability of muscles and nerves in that compartment. this condition arises due to compromised blood flow and localized ischemia (9). although, there has not been sufficient evidence regarding its incidence rate in rm, it’s not considered to be a rare complication (4). hence, it is crucial to closely monitor clinical signs and compartment pressures with respect to compartment syndrome, as it has the potential to progress into a surgical emergency. disseminated intravascular coagulation is drastic activation of the coagulation system, leading to microvascular thrombosis and potentially life-threatening hemorrhage due to consumption of coagulation factors and platelets (10). the release of thromboplastin and other substances with prothrombotic properties from the injured muscle tissue in rm, especially severe forms of it, can cause dic (4). due to the fact that dic mostly occurs as a complication of severe medical conditions, its prevalence remains higher in more severe settings (11). in this article our primary goal is to conduct an epidemiologic systematic review on published literature to report the prevalence of compartment syndrome and dic in patients with rm based on the rm’s etiology. our secondary goal is to conduct a meta-analysis, if adequate data is available, to determine the pooled prevalence of these complications following rm. 2. methods 2.1. study design and setting the present study is a systematic review of observational studies conducted with the aim of investigating the prevalence of compartment syndrome and dic in patients with rm. since this systematic review is dedicated to just reporting the prevalence of an event in observational studies there is no comparison of data in this research. this systematic review conforms to the “preferred reporting items for systematic reviews and meta-analyses” (prisma) statement (12). this study follows the guidelines for meta-analyses and systematic reviews of observational studies in epidemiology (moose) (13). 2.2. search strategy to find an answer to the question of the present study, medline, embase, and scopus databases were searched. keywords related to compartment syndrome, dic, and rhabdomyolysis were selected and then searched in each database with the appropriate combination. the keywords of search strategy for this study are reported in supplementary table 1. the search was conducted on april 30, 2023 and included every record till then. in addition to the systematic search, a manual search was also performed in gray literature. the search strategy is presented in the appendix. 2.3. selection criteria two reviewers, i.n. and m.f.r independently screened the records by title/abstract and full text to exclude records unrelated to the topic. a third reviewer, b.d., would decide if the two reviews couldn’t agree on a particular article. cohort studies and cross-sectional studies in english, which conducted research on the prevalence of compartment syndrome and dic in patients with rm were included in the present study. exclusion criteria were failure to report compartment syndrome or dic as an outcome, not identifying rm’s etiologies, clinical trials, case-control studies, case reports, review studies, repeated studies, retracted studies, conference abstracts, editorials, and letters to editors. 2.4. quality assessment assessment of the quality of included articles was done by two reviewers, b.d. and m.f.r., using the national heart, lung, and blood institute (nhlbi) quality assessment tools for observational cohort and cross-sectional studies (14). this tool is a 14-question checklist, based on which the quality of articles is assessed in terms of methodology, report of findings, and possible distortions. a third reviewer, a.s., would decide if the two reviews couldn’t agree on a particular assessment. 2.5. data extraction compartment syndrome and dic prevalence were extracted from included articles, along with the etiology of rhabdomyolysis, age group of patients, and studies’ demographic information such as data collection period, country, study design, and sampling method. we also collected data on definitions of these conditions in the included articles, when available. collected data were summarized using a checklist designed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e55 based on the moose statement guidelines (13). 2.6. statistical analysis the prevalence of compartment syndrome and dic in rm patients was investigated using the comprehensive metaanalysis software, version 2.0 (biostat inc., englewood, nj, usa). we reported pooled prevalence with a 95% confidence interval (ci). random effect model was used for groups of studies with significant heterogeneity between their research methodologies; and for groups of studies without significant heterogeneity, fixed effect model was used. in addition, if possible, subgroup analysis was performed based on the etiology and severity of rm. finally, funnel plot and egger’s test were used to identify publication bias. 3. results at the last stage of our screenings there were 20 articles, which were included in our systematic review via selection process (figure 1). six of them were conducted in usa (1520), two in australia (21, 22), two in norway (23, 24), and 10 in other countries, which can be seen in table 1. all studies were retrospective cohorts except one, which was crosssectional (25). the sampling method in all of the included studies were consecutive. 17 studies consisted only of adult patients (18 years old or above) and the three remaining studies consisted of children as well as adults. the total number of rm patients in these studies were 1310 patients, approximately 55% of which were male. quality of included articles was assessed based on nhlbi quality assessment tool (supplementary table 2). included articles were rated as poor quality (0 to 4 out of 14 questions), fair quality (5 to 10 out of 14 questions), or good quality (11 to 14 out of 14 questions). all included studies had fair quality. 3.1. compartment syndrome prevalence in included studies sixteen of the included studies reported compartment syndrome prevalence in rm patients. there were 928 adults with rm in these studies, approximately 54% of which were male. rm definitions were different in these studies. one study defined rm patients as having international classification of diseases (icd) version 9 code related to rm diagnosis (17). other studies defined rm disease by the level of the creatine kinase (ck) enzyme in blood of the patients. most authors diagnosed rhabdomyolysis based on ck levels five times the upper limit of normal levels (>1000 u/l) (16, 19, 20, 22, 23, 25-28). this diagnostic cut-off was lower than 1000 in one study (15), and four studies exclusively included patients with ck levels more than 5000 (15, 21, 24, 29, 30). ck level more than 5000 is considered to indicate severe rm (31). the criteria for rm definition were not available in one study (32). the primary etiologies in these patients comprise exercise, earthquake-related trauma, snake venom, drug toxicity, prolonged immobilization, and surgery (table 2). the compartment syndrome definition was not reported in most of the included articles. one study mentioned clinical diagnosis by a surgeon (24) and another one mentioned requirement of fasciotomy (22) as compartment syndrome diagnosis method. the rate of compartment syndrome in the included studies ranged from 0% to 30.7%. the pooled prevalence of compartment syndrome was 4% (95% ci: 2.20 to 7.40; p < 0.001) in these studies (figure 2). due to the high levels of heterogeneity between these studies we tried to conduct a sub-group analysis based on rm severity, and rm etiology dividing rm causes between traumatic and non-traumatic etiologies. traumatic causes included exercise, earthquake trauma, prolonged immobilization, and surgery. the pooled prevalence of compartment syndrome in severe rm cases was 7.1% (95% ci: 2.90 to 16.00; p < 0.001; supplementary figure 1). the pooled prevalence of this complication in trauma-induced rm was 4.4% (95% ci: 1.80 to 10.00, p < 0.001; supplementary figure 2). finally, the publication bias was investigated via funnel plot and egger’s test, which showed no significant publication bias (supplementary figure 3). 3.2. dic prevalence in included studies ten of the included studies reported the prevalence of dic syndrome or related hematologic failures in rm patients. there were 797 patients with rm in these studies, approximately 53% of which were male. rm definitions were different in these studies. the rm definition in one study was based on international classification of diseases (icd) version 9 code related to rm diagnosis (18). like in articles related to compartment syndrome, most studies diagnosed rhabdomyolysis based on ck levels five times the upper limit of normal levels (>1000 u/l) (19, 26, 27, 33-35). two studies exclusively included patients with ck levels more than 5000 (24, 29). criteria for rm diagnosis were not available in one study (32). the primary etiologies in these patients comprised exercise, salicylate intoxication, snake venom, drug toxicity, mushroom poisoning, and exertional heat stroke, as shown in table 3. the dic syndrome definition was not reported in most of the included articles. korean society on thrombosis and hemostasis (ksth) dic scoring system and international society for thrombosis and hemostasis (isth) dic scoring system were used as criteria for dic syndrome diagnosis in two of the studies (26, 35). one study only mentioned hematologic failure as outcome of rm (18). dic syndrome prevalence in rm patients in the included studies ranged from 0% to 40.47%. our meta-analysis showed the pooled prevalence of 8.3% (95% ci: 03.90 to 16.50; p < 0.001) in all studies (figure 3). due to the high levels this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. danaei et al. 4 of heterogeneity between these studies, we tried to conduct a sub-group analysis based on rm severity and etiology. however, because of the insufficient number of studies in these sub-groups it was not possible. publication bias was investigated using funnel plot and egger’s test, which revealed no significant publication bias in the included studies (supplementary figure 4). 4. discussion compartment syndrome and disseminated intravascular coagulation are two of the serious complications that can arise following rhabdomyolysis (36-38). if these complications occur, they can significantly impact the prognosis of the disease and result in morbidity and mortality for rm patients (39). compartment syndrome is not a rare finding in rhabdomyolysis (4). it can induce ischemia in the affected area, impeding the healing process and exacerbating rm in a selfperpetuating vicious loop (40, 41). dic can trigger systemic hematologic and circulatory dysfunction, giving rise to lifethreatening events such as severe hemorrhage and organ failure (42). therefore, it is important to investigate the occurrence rate of these complications among individuals with rhabdomyolysis. the overall prevalence of compartment syndrome in our study was calculated to be 4% (95% ci: 2.20 to 7.40). it has been shown that the majority of cases of acute compartment syndrome occur after trauma, with an estimated incidence of 7.3 per 100,000 in males and 0.7 per 100,000 in females (9). as we showed in this systematic review, it can result from rhabdomyolysis with both traumatic and non-traumatic origins. however, the rate of compartment syndrome was much higher in the study that included patients with rm due to the earthquake trauma (25). the pooled prevalence of this complication in exclusive trauma-induced rm was 4.4% (95% ci: 1.80 to 10.00) in our study, which is close to overall prevalence. the pooled prevalence of compartment syndrome calculated from studies exclusively reporting severe rm was 7.1% (95% ci: 2.90 to 16.00) and the etiology of rm in all of them was exercise. we classified severe rhabdomyolysis as having creatine kinase (ck) levels exceeding 5000 iu/l. other studies also have reported that ck levels higher than 4000 iu/l are associated with compartment syndrome (43, 44). in the present study, pooled prevalence of dic syndrome was calculated to be 8.3% (95% ci: 03.90 to 16.50). direct comparison and analysis of the incidence of dic across studies is challenging due to various factors. for instance, diagnostic scoring systems for dic are not consistently utilized in all hospitals, and different criteria have been employed to diagnose it (10). the studies in this field may underestimate the actual prevalence of dic, especially mild, subclinical, and transient episodes, since they might have no clinical manifestations (4). in one study conducted in japan the rate of dic was reported to be 1% in hospitalized patients (45). this rate was reported to be approximately 10 to 30% in intensive care unit (icu) patients (46-50). studies also suggested approximate rate of 8 to 33% in patients resuscitated from outof-hospital cardiac arrest (51, 52) and 36 to 41% in patients with head trauma (53, 54). our study holds some limitations. the small population size in the included studies and the limited number of these studies were limitations that needed to be noticed. many articles on dic and compartment syndrome prevalence pertained to single-center studies, lacked specific definitions of these complications, were published long ago, and did not provide evidence on presence of confounding factors and comorbidities that can play a role in occurrence of these complications. these limitations highlight the need of new researches on the epidemiology of dic and compartment syndrome in rhabdomyolysis patients with larger population and utilizing standard diagnostic criteria to report their incidence. furthermore, conduction of meta-analysis on observational studies is challenging due to the inherent limitations of the observational studies. observational studies cannot address all potential confounding factors and the heterogeneity among these studies is usually high. despite efforts to maintain methodological consistency and control for confounding factors, such as sub-group analysis and using random effects model, complete homogeneity cannot be achieved (55). further studies are needed to investigate prevalence and tolls of these complications in larger populations of rm patients. 5. conclusion according to our results the pooled prevalence of compartment syndrome and dic in rm patients were 4% (95% ci: 2.20 to 7.40) and 8.3% (95% ci: 03.90 to 16.50) respectively. the rate of compartment syndrome was slightly higher in patients with severe rm and its rate in patients with traumatic rm was close to the overall rate of compartment syndrome in all rm patients. 6. declarations 6.1. acknowledgments not applicable. 6.2. conflict of interest the authors declare no competing interests. 6.3. funding and support none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e55 6.4. authors’ contribution all the authors met the criteria of authorship based on the recommendations of the 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48. gando s, saitoh d, ogura h, mayumi t, koseki k, ikeda t, et al. natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. crit care med. 2008;36(1):145-50. 49. sivula m, tallgren m, pettila v. modified score for disseminated intravascular coagulation in the critically ill. intensive care med. 2005;31(9):1209-14. 50. toh ch, downey c. performance and prognostic importance of a new clinical and laboratory scoring system for identifying non-overt disseminated intravascular coagulation. blood coagul fibrinolysis. 2005;16(1):69-74. 51. buchtele n, schober a, schoergenhofer c, spiel ao, mauracher l, weiser c, et al. added value of the dic score and of d-dimer to predict outcome after successfully resuscitated out-of-hospital cardiac arrest. eur j intern med. 2018;57:44-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e55 52. kim j, kim k, lee jh, jo yh, kim t, rhee je, et al. prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest. resuscitation. 2013;84(1):48-53. 53. sun y, wang j, wu x, xi c, gai y, liu h, et al. validating the incidence of coagulopathy and disseminated intravascular coagulation in patients with traumatic brain injury– analysis of 242 cases. br j neurosurg. 2011;25(3):363-8. 54. hulka f, mullins rj, frank eh. blunt brain injury activates the coagulation process. arch surg. 1996;131(9):923-7; discussion 7-8. 55. metelli s, chaimani a. challenges in meta-analyses with observational studies. evid based ment health. 2020;23(2):83-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. danaei et al. 8 table 1: characteristics of included articles authors publication year study period country study design age group sampling method arnautovic et al. (15) 2018 2014-2016 usa r-cohort adult consecutive bäcker et al. (16) 2019 2012-2017 usa r-cohort adult consecutive cutler et al. (17) 2015 2010-2014 usa r-cohort adult consecutive hernández-contreras et al. (32) 2015 2012-2013 spain r-cohort adult consecutive huynh et al. (21) 2016 2013-2014 australia r-cohort adult consecutive jabur et al. (29) 2018 2009-2015 uae r-cohort adult consecutive kaewput et al. (18) 2021 2003-2014 usa r-cohort all ages consecutive li et al. (25) 2021 2016-2016 taiwan cross-sectional adult consecutive luetmer et al. (19) 2020 2003-2015 usa r-cohort adult consecutive moon et al. (26) 2023 2010-2021 korea r-cohort adult consecutive nishimura et al. (33) 2016 2003-2014 japan r-cohort adult consecutive o’connor et al. (20) 2014 2010-2013 usa r-cohort all ages consecutive rogliano et al. (27) 2020 2012-2018 france r-cohort adult consecutive shroff et al. (30) 2022 2018-2019 singapore r-cohort adult consecutive tazmini et al. (24) 2017 2011-2015 norway r-cohort adult consecutive trakulsrichai et al. (34) 2020 2012-2016 thailand r-cohort all ages consecutive vangstad et al. (23) 2017 2003-2012 norway r-cohort adult consecutive wang et al. (35) 2021 2008-2019 china r-cohort adult consecutive yim et al. (22) 2019 2013-2017 australia r-cohort adult consecutive youssef et al. (28) 2010 2007-2009 egypt r-cohort adult consecutive r-cohort: retrospective cohort. table 2: compartment syndrome prevalence in rhabdomyolysis patients authors rm definition male n(%) rm etiology cs definition cs prevalence n(%) arnautovic et al. (15) ck > 342 41 (33) exercise nr 0 (0) bäcker et al. (16) ck ≥ 1000 42 (36) exercise nr 0 (0) cutler et al. (17) icd-9 code 728.88 29 (18) exercise nr 2 (6.89) hernández-contreras et al. (32) nr 11 (5) exercise nr 0 (0) huynh et al. (21) ck ≥ 25000 12 (11) exercise nr 1 (8.33) jabur et al. (29) ck > 5000 25 (25) exercise nr 3 (12) li et al. (25) ck more than 5 times the uln value 13 (nr) earthquake trauma nr 4 (30.76) luetmer et al. (19) ck > 1000 21 (18) exercise nr 0 (0) moon et al. (26) ck ≥ 1000 90 (nr) snake venom nr 1 (1.11) o’connor et al. (20) ck > 1000 43 (nr) stimulant drugs toxicity nr 3 (6.97) rogliano et al. (27) ck ≥ 1000 237 (138) drug poisoning nr 5 (2.11) shroff et al. (30) ck > 20000 43 (21) exercise nr 0 (0) tazmini et al. (24) ck > 5000 31 (15) exercise clinical diagnosis by a surgeon 0 (0) vangstad et al. (23) male (18-49 years): ck > 2000 male (age > 49 years): ck > 1400 female: ck > 1050 204 (130) prolonged immobilization nr 1 (0.49) yim et al. (22) ck > 1000 79 (54) illicit drug use requirement of fasciotomy due to cs 3 (3.79) youssef et al. (28) ck > 1000 7 (4) roux-en-y gastric bypass bariatric surgery nr 0 (0) rm: rhabdomyolysis; ck: creatine kinase; uln: upper limit of normal; cs: compartment syndrome; nr: not reported; icd-9: international classification of diseases version 9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e55 table 3: disseminated intravascular coagulation (dic) prevalence in rhabdomyolysis patients authors rm definition male n(%) rm etiology dic definition dic prevalence n(%) hernández-contreras et al. (32) nr 11 (5) exercise nr 0 (0) jabur et al. (29) ck > 5000 25 (25) exercise nr 0 (0) kaewput et al. (18) identified by the icd-9 diagnosis 728.88 258 (136) salicylate intoxication hematological failure 30 (11.62) luetmer et al. (19) ck > 1000 21 (18) exercise nr 1 (4.76) moon et al. (26) ck ≥ 1000 90 (nr) snake venom ksth dic scoring system 1 (1.11) nishimura et al. (33) ck more than 5 times the uln value 7 (nr) snake venom nr 1 (14.28) rogliano et al. (27) ck ≥ 1000 237 (138) drug poisoning nr 29 (12.23) tazmini et al. (24) ck > 5000 31 (15) exercise nr 0 (0) trakulsrichai et al. (34) ck > 1000 33 (nr) mushroom poisoning nr 1 (3.03) wang et al. (35) ck > 1000 84 (84) exertional heatstroke isth dic scoring system 34 (40.47) rm: rhabdomyolysis; ck: creatine kinase; uln: upper limit of normal; nr: not reported; icd-9: international classification of diseases version 9; ksth: korean society on thrombosis and hemostasis; isth: international society for thrombosis and hemostasis. supplementary figure 1: meta-analysis on rate of compartment syndrome in studies including patients with severe rhabdomyolysis. overall heterogeneity: i2 = 23.12%, p-value = 0.27. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. danaei et al. 10 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flow chart of the studies identified and included in the systematic review. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e55 figure 2: results of meta-analysis of compartment syndrome prevalence in rhabdomyolysis patients. ci: confidence interval. figure 3: results of meta-analysis of disseminated intravascular coagulation (dic) syndrome prevalence in rhabdomyolysis patients. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index b. danaei et al. 12 supplementary figure 2: meta-analysis on rate of compartment syndrome in studies including patients with traumatic rhabdomyolysis. overall heterogeneity: i2 = 54.54%, p-value = 0.01. ci: confidence interval. supplementary figure 3: publication bias assessment of included studies reporting compartment syndrome prevalence. egger’s regression test: intercept = -1.18, standard error = 0.90, p-value (2-tailed) = 0.21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e55 supplementary figure 4: publication bias assessment of included studies reporting disseminated intravascular coagulation (dic) syndrome prevalence. egger’s regression test: intercept = -1.69, standard error = 1.28, p-value (2-tailed) = 0.23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 22 emergency (2014); 2 (1): 22-25 original research qt interval in pregnant and non-pregnant women majid zamani1, mehrdad esmailian1, zahra yoosefian2* 1. department of emergency medicine, isfahan university of medical sciences, isfahan, iran 2. department of emergency medicine, shiraz university of medical sciences, shiraz, iran abstract introduction: prolongation of qt interval might result in dangerous cardiac arrhythmias, including torsades de pointes (tdp), consequently leading to syncope or death. a limited number of studies carried out in this respect to date have shown that qt interval might increase during pregnancy. on the other hand, it has been shown that each pregnancy might result in an increase in the risk of cardiac accidents in patients with long qt interval. therefore, the present study was undertaken to compare qt intervals in pregnant and non-pregnant women. methods: pregnant women group consisted of 40 women in the second and third trimesters of pregnancy and the non-pregnant control group consisted of healthy women 18-35 years of age. all the patients underwent standard 12-lead electrocardiogram (ecg). the qt interval was measured for each patient at lead ii. the mean corrected qt interval (qtc) and qt dispersions (qtd) were compared between the two groups. results: mean heart rates in the pregnant and non-pregnant groups were 98.55±14.09 and 72.53±13.17 beats/minutes (p<0.001). qtd and qtc means were in the normal range in both groups; however, these variables were 49.50±12.80 and 43.03±18.47 milliseconds in the pregnant group and 39.5±9.59 and 40.38±17.20 milliseconds in the control group, respectively (p<0.001). conclusion: the qt interval was longer in pregnant women compared to nonpregnant women; however, it was in the normal range in both groups. therefore, it is important to monitor and manage risk factors involved in prolongation of qt interval and prevent concurrence of these factors with pregnancy. key words: pregnancy; electrocardiography; arrhythmias; ventricular tachycardia cite this article as: zamani m, esmailian m, yoosefian z. qt interval in pregnant and non-pregnant women. emergency. 2014;2(1):22-5. introduction:1 ong qt syndrome, which is characterized by an increase in qt interval on electrocardiogram (ecg), makes patients susceptible to cardiac arrhythmias, including torsades de pointes (tdp), followed by repeated syncope episodes and even sudden death (1). the syndrome has two forms: hereditary and acquired. the hereditary form is a familial genetic canalopathy (2) and the acquired form is a reversible condition induced by an environmental factor, usually a drug from various groups, including some antihistamines, antibiotics, antipsychotic drugs or gastrointestinal prokinetics (3). in addition, several risk factors have been identified involved in prolongation of qt interval and the related arrhythmias, which include hypokalemia, hypomagnesemia, hypothyroidism, and hemodialysis. concurrence of these factors can increase the risk of ventricular arrhythmia and the subsequent accidents. therefore, in patients with these risk factors care should be exercised in concomitant prescription of the drugs mentioned above (1). corrected qt (qtc) and qt *corresponding author: zahra yoosefian, department of emergency medicine, beheshti hospital, vali-asr avenue, shiraz, iran; tel: 00989131059813 email address: yoosefian@sums.ac.ir received: 10 december 2013; accepted: 21 january 2013 dispersion (qtd) indexes are used to evaluate the qt index; qtc is used to correspond the qt interval with the heart rate and both in fact show various dimensions of ventricular repolarization (4). various physiologic changes occur during pregnancy, including changes in the cardiovascular system. cardiac arrhythmias are not uncommon during pregnancy and might create different problems for the mother and the fetus (5). on the other hand, female gender is considered as an independent risk factor for long qt syndrome; in this context, qt interval is almost 10% longer in adult females. various studies have introduced sex hormones (both male and female) as a factor effective on the qt interval (6-9). considering hormonal changes occurring during the pregnancy, it is possible for the qt interval to be affected. insufficient data is available in relation to the effect of pregnancy on qt interval. although the interval is expected to be decreased in pregnancy due to tachycardia, some studies have shown that the interval increases in pregnant women (10). lechmanova et al. explained the reasons for an increase in qt and qtd intervals in pregnancy as follows: enlarged abdominal organs, hormonal and sympathetic changes, and finally an increase in the impedance of tissues located between the heart and the body surface due to the gradual acl this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 23 zamani et al cumulation of water and sodium during pregnancy (10). on the other hand, studies have shown that patients with long qt syndrome (lqts) run a higher risk of developing tdp immediately after pregnancy (11-13). based on above-mentioned, the present study was designed to evaluate and compare the qt interval in pregnant and non-pregnant women to assess the effect of pregnancy on qt interval. methods: study design and setting this prospective cohort study was carried out from april 2011 to december 2012 in shahid behesthi hospital, shiraz, iran. the protocol of the study was approved by shiraz university of medical sciences and the ethics committee of the same university. informed consent forms were taken from all the subjects. participants the subjects were randomly selected from women referring to the clinic for routine pregnancy examinations. in addition, the control group subjects were randomly selected from the individuals accompanying patients referring to the clinic. 40 women in the second and third trimesters of pregnancy (over 13 weeks of gestational age according to a sonographic examination of the first trimester) were included in the pregnant women group and 40 non-pregnant women who were in their fertile years were included in the control group. inclusion criteria of the study were an age range of 1835 years, interest in and ability to take part in the study, an interval of at least one year between the present pregnancy and the previous one. in addition, exclusion criteria were the presence of any arrhythmia in ecg, use of any medication influencing qt interval, affliction with any cardiac and renal disease. data collection serial evaluation of ecgs was carried out and the cardiac enzymes, including troponin i and cardiac isoenzymes creatine kinase, were checked. cardiac enzymes were evaluated every six hours up to three times. in addition, ecgs were evaluated whenever chest pain recurred. the age, gender, marital status, occupation, living place and phone number of patients were questioned and registered. they were asked to refer to the exercise test unit of imam hossein hospital during one week after discharging. when the patients returned to the exercise test unit, they were asked about the incidence of cardiac symptoms and signs, recurrence of chest pain or referring to the treatment center again. after the exercise test, the results were collected and patients with positive test underwent angiography. then, the patients were followed for a month. at the time of discharge, the patients or their relatives received instructions in relation to the symptoms and signs of cardiac diseases. endpoints history of medications used and cardiac diseases, the patients’ demographic data, and the gestational ages were recorded. all the subjects were questioned in relation to the occurrence of any of the symptoms and signs of syncope, palpitation, vertigo, angina, and asthma (a collection of symptoms and signs, which might have a cardiac origin) in the six-month period before taking part in the study for the control group and at the beginning of pregnancy for the pregnant group. a standard 12-lead ecg (paper speed of 25 mm/s and a current of 0.5 mv/cm) was recorded from each subject. the qt interval, from the beginning of q to the end of t, was measured and recorded. then bazett’s formula, qtc=qt/√rr, was used to match the interval with the heart rate. qt dispersion (qtd) was also calculated as the difference between the maximum and minimum qt intervals in a 12-lead ecg (4). the ecgs were also used to determine the presence or absence of any arrhythmia and the axes of qrs and p waves. statistical analysis data were collected, sorted and analyzed with spss 18. independent t-test was used to compare continuous data between the two groups. chi-squared test was used to compare qualitative data and frequencies of symptoms and signs between the two groups. descriptive data were presented as means ± sd. statistical significance was defined at p<0.05. results: eighty subjects participated in the present study: 40 in the pregnant women group and 40 in the control group, with mean ages of 29±2.8 and 28±3.2 years, respectively. the mean gestational age of pregnant women was 29.21±7.40 weeks (19-42). sixteen patients (41%) had their first pregnancy, 134 (33.3%) second pregnancy, eight (20.5%) third pregnancy, one (2.6%) fourth pregnancy and one (2.6%) fifth pregnancy. qrs and p waves of all the subjects were in the normal range, with no significant differences between the two groups (p>0.05). qtc and qtd were higher in the pregnant group versus the control (0.001). it should be pointed out that the means of these two variables were in the normal range. table 1 presents the details of comparisons of qtc, qtd, and heart rates between the two groups. in general, there were no significant differences between the means of qtc and qtd between pregnant women in their second trimesters and those in their third trimesters (p>0.05) (table 2). discussion: the results of present study showed a longer qt interval in pregnant women versus non-pregnant. however, qtd and qtc means were in the normal range in both groups. a research in available library and electronic sources showed only a limited number of studies with similar themes. there are some studies on the effect of pregnancy on patients with lqts (12-16). lechmanova et al. (2002) evaluated qt interval and t-loop morphology in pregnant and non-pregnant women. they com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (1): 22-25 24 pared 37 healthy pregnant women with gestational ages of 36-40 weeks with 18 healthy non-pregnant women. all the subjects underwent electrocardiography and vectorcardiography evaluations. finally, it was concluded that qtc and qtd were significantly higher in pregnant women compared to the control group (10), consistent with the results of the present study. isezuo et al. (2004) evaluated and compared qt intervals between pregnant women with and without eclampsia. they did not make comparisons with the control nonpregnant women. in general, the mean qtc in the group with eclampsia (47.0 milliseconds) and the group without it (43.6 milliseconds) was higher than that in the present study (41.75 milliseconds) (17). seth et al. concluded that pregnant women with a previous definitive diagnosis of lqts run a lower risk of cardiac accidents during pregnancy, including syncope and sudden death due to cardiac arrest. however, during the first nine months after delivery, the risk of cardiac accidents, especially life-threatening accidents, increases. after this period, the risk level returns to the baseline before pregnancy (13). rashba et al. (1998) reported similar results (12). none of the two studies above evaluated the question whether the qt interval changes during pregnancy or after it. seth et al. described the reason for a decrease in cardiac accidents due to lqts during pregnancy and an increase in such accidents after pregnancy as follows: pregnancy results in an increase in the referral of women to health and treatment centers, which might lead to prevention of cardiac accidents. on the other hand, although the qt intervals were not different between nulliparous women and those with previous pregnancies, women with no history of delivery before the age of 15 had experienced more cardiac accidents and received more treatments with β-blockers, all of which might have prompted them to refrain from becoming pregnant (13). during the period after delivery, hemodynamic changes occur, which might be related to an increase in arrhythmias. for example, cardiac output, which increases significantly during pregnancy, decreases suddenly. rashba et al. proposed the hypothesis that an increase in cardiac accidents in patients with lqts after delivery might be attributed to a change in adrenergic activity. they also reported that an increase in heart rate during pregnancy could have a protective effect in patients with lqts, who might have a longer qt interval at lower heart rates; after delivery, this rate returns to the baseline. therefore, this protective role is negated, increasing the odds of qt interval prolongation, and incidence of arrhythmias (12). some other studies have shown that other factors such as an increase in stress, fatigue, insomnia, and other environmental factors are effective in increasing the risk of cardiac accidents due to lqts during pregnancy. another opinion about the possible cause of the relationship between pregnancy and a change in qt interval is the relation between sex hormones and ventricular repolarization. several studies have evaluated this relationship but no definitive results have been achieved. one of the risk is that both exogenous and endogenous sex hormones can influence qt interval (6, 7, 18, 19). in general, during sexual maturation the qt interval is shortened about 20 milliseconds in males; however, it does not undergo any changes in females. in fact, the qt interval is not significantly different between the two sexes and the shortening during sexual maturation is responsible for the difference (20). some studies have suggested that testosterone is related to shorter repolarization in men (21). based on a report by naagawa et al. the qt interval in the luteal phase is shorter than that in the follicular phase, which might be attributed to the effect of progesterone (18). therefore, it is possible that the qt interval is influenced by hormonal changes due to pregnancy. however, some studies have shown that hormonal changes in pregnancy decrease the risk of tdp in patable 1: comparisons of qtc, qtd, and heart rates between the pregnant and non-pregnant groups  variables groups minimum maximum mean±sd p heart rate pregnant 68 130 98.55±14.09 <0.001 control 51 118 72.53±13.17 qtd pregnant 30 80 49.50±12.80 <0.001 control 20 60 39.50±9.59 qtc pregnant 380 460 430.30±18.47 <0.001 control 370 440 403.80±17.20 table 2: comparison of qtc and qtd between the second and third trimesters  p mean ± sd number of patients trimester variable 0.726 431.3±15.98 17 second qtc 429.1±20.43 23 third 0.915 48.67±11.80 17 second qtd 49.13±13.78 23 third this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 25 zamani et al tients with ltqs (13). one of the limitations of the present study was the unavailability of the patients’ previous ecgs for making comparisons. on the other hand, there were limitations in the selection of controls; selection of controls from first-degree relatives was more logical and not possible. further studies are necessary to confirm or refute the results of the present study. conclusion: the qt interval in pregnant women was in the normal range but longer compared to non-pregnant women. therefore, other factors that might be involved in prolongation of the qt interval should be taken into account and care should be exercised to prevent their concurrence with pregnancy as far as possible. acknowledgments: we would like to thanks outpatient clinic staffs of beheshti hospital for helping us. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of international committee of medical journal editors. references: 1. kallergis em, goudis ca, simantirakis en, kochiadakis ge, vardas pe. mechanisms, risk factors, and management of acquired long qt syndrome: a comprehensive review. scientificworldjournal. 2012;2012:1-8. 2. sauer aj, moss aj, mcnitt s, et al. long qt syndrome in adults. j am coll cardiol. 2007;49(3):329-37. 3. van noord c, eijgelsheim m, stricker bhc. drug-and non-drug-associated qt interval prolongation. br j clin pharmacol. 2010;70(1):16-23. 4. malik m, batchvarov vn. measurement, interpretation and clinical potential of qt dispersion. j am coll cardiol. 2000;36(6):1749-66. 5. li jm, nguyen c, joglar ja, hamdan mh, page rl. frequency and outcome of arrhythmias complicating admission during pregnancy: experience from a high-volume and ethnically-diverse obstetric service. clin cardiol. 2008;31 (11):53841. 6. carnethon mr, anthony ms, cascio we, et al. a prospective evaluation of the risk of qt prolongation with hormone replacement therapy: the atherosclerosis risk in communities study. ann epidemiol. 2003;13(7):530-6. 7. kadish ah, greenland p, limacher mc, frishman wh, daugherty sa, schwartz jb. estrogen and progestin use and the qt interval in postmenopausal women. ann noninvasive electrocardiol. 2004;9(4):366-74. 8. saito t, ciobotaru a, bopassa jc, toro l, stefani e, eghbali m. estrogen contributes to gender differences in mouse ventricular repolarization. circ res. 2009;105(4):343-52. 9. sedlak t, shufelt c, iribarren c, merz cn. sex hormones and the qt interval: a review. j womens health (larchmt). 2012; 21(9):933-41. 10. lechmanová m, kittnar o, mlcek m, et al. qt dispersion and t-loop morphology in late pregnancy and after delivery. physiol res. 2002;51(2):121-30. 11. meregalli p, westendorp i, tan h, elsman p, kok w, wilde a. pregnancy and the risk of torsades de pointes in congenital long-qt syndrome. neth heart j. 2008;16(12):422-5. 12. rashba ej, zareba w, moss aj, et al. influence of pregnancy on the risk for cardiac events in patients with hereditary long qt syndrome. circulation. 1998;97(5):451-6. 13. seth r, moss aj, mcnitt s, et al. long qt syndrome and pregnancy. j am coll cardiol. 2007;49(10):1092-8. 14. heradien mj, goosen a, crotti l, et al. does pregnancy increase cardiac risk for lqt1 patients with the kcnq1a341v mutation? j am coll cardiol. 2006;48(7):1410-5. 15. khositseth a, tester dj, will ml, bell cm, ackerman mj. identification of a common genetic substrate underlying postpartum cardiac events in congenital long qt syndrome. heart rhythm. 2004;1(1):60-4. 16. kukla p, filipecki a, jastrzebski m, et al. long qt syndrome in the postpartum period]. kardiol pol. 2009;67(7):795-9. [polish]. 17. isezuo s, ekele b. eclampsia and abnormal qtc. west afr j med. 2004;23(2):123-7. 18. nakagawa m, ooie t, takahashi n, et al. influence of menstrual cycle on qt interval dynamics. pacing clin electrophysiol. 2006;29(6):607-13. 19. rodriguez i, kilborn mj, liu x-k, pezzullo jc, woosley rl. drug-induced qt prolongation in women during the menstrual cycle. jama. 2001;285(10):1322-6. 20. rautaharju p, zhou s, wong s, et al. sex differences in the evolution of the electrocardiographic qt interval with age. can j cardiol. 1992;8(7):690-5. 21. van noord c, dörr m, sturkenboom mc, et al. the association of serum testosterone levels and ventricular repolarization. eur j epidemiol. 2010;25(1):21-8. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 78 emergency (2016); 4 (2): 78-82 original research effective factors in severity of traffic accident-related traumas; an epidemiologic study based on the haddon matrix kambiz masoumi1, arash forouzan1*, hassan barzegari1, ali asgari darian1, fakher rahim2, behzad zohrevandi3, somayeh nabi1 1. emergency department, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. institute of health research, thalassemia and hemoglobinopathies research center, ahvaz jundishapur university of medical sciences, ahvaz, iran. 3. road trauma research center, guilan university of medical sciences, rasht, iran. *corresponding author: arash forouzan; department of emergency medicine, imam khomeini general hospital, azadegan avenue, ahvaz, khuzestan province, 6193673166, iran; tel/fax: +986112229166; email: md_89864@yahoo.com received: april 2015; accepted: june 2015 abstract introduction: traffic accidents are the 8th cause of mortality in different countries and are expected to rise to the 3rd rank by 2020. based on the haddon matrix numerous factors such as environment, host, and agent can affect the severity of traffic-related traumas. therefore, the present study aimed to evaluate the effective factors in severity of these traumas based on haddon matrix. methods: in the present 1-month cross-sectional study, all the patients injured in traffic accidents, who were referred to the ed of imam khomeini and golestan hospitals, ahvaz, iran, during march 2013 were evaluated. based on the haddon matrix, effective factors in accident occurrence were defined in 3 groups of host, agent, and environment. demographic data of the patients and data regarding haddon risk factors were extracted and analyzed using spss version 20. results: 700 injured people with the mean age of 29.66 ± 12.64 years (3-82) were evaluated (92.4% male). trauma mechanism was car-pedestrian in 308 (44%) of the cases and car-motorcycle in 175 (25%). 610 (87.1%) cases were traffic accidents and 371 (53%) occurred in the time between 2 pm and 8 pm. violation of speed limit was the most common violation with 570 (81.4%) cases, followed by violation of right-of-way in 57 (8.1%) patients. 59.9% of the severe and critical injuries had occurred on road accidents, while 61.3% of the injuries caused by traffic accidents were mild to moderate (p < 0.001). the most common mechanisms of trauma for critical injuries were rollover (72.5%), motorcycle-pedestrian (23.8%), and car-motorcycle (13.14%) accidents (p < 0.001). conclusion: based on the results of the present study, the most important effective factors in severity of traffic accident-related traumas were age over 50, not using safety tools, and undertaking among host-related factors; insufficient environment safety, road accidents and time between 2 pm and 8 pm among environmental factors; and finally, rollover, car-pedestrian, and motorcycle-pedestrian accidents among the agent factors. keywords: wounds and injuries; accidents; accidents, traffic; risk factors cite this article as: masoumi k, forouzan a, barzegari h, et al. effective factors in severity of traffic accident-related traumas; an epidemiologic study based on the haddon matrix. emergency. 2016; 4(2):78-82. introduction: raffic accidents are one of the major causes of disability and mortality in different countries and are considered the 8th cause of mortality in the industrial countries. based on a statement by world health organization (who) it is expected to rise to the 3rd rank by 2020 (1, 2). traffic accidents not only cause millions of disabilities and deaths, and take a toll on the countries’ finance, but are also considered a big problem in the way of improving public health (3-7). numerous factors such as environmental, vehicle-related, host (driver, pedestrian), and their type of interaction affect the characteristics of these accidents. to accurately identify them, there are solutions such as evaluation of public health, risk factors, and haddon matrix (8). among the mentioned solutions, haddon matrix is the best tool to combine the epidemiologic triangle of the host, agent and environment with 3 stages of prevention before, during and after the accident (9). based on this tool, special strategies can be designed for road traffic injury prevent this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 79 emergency (2016); 4 (2): 78-82 tion. various studies show that in traffic accidents, pedestrians and young motorcycle riders are most susceptible to injury. a cross-sectional study that evaluated traffic accident injuries over one year, showed that about 98.9% of the injured were men with the mean age of 30 years (10). a similar study revealed that factors such as age over 45 years, weather condition, type of accident and road conditions significantly correlated with severity of injury (11). in a study by hatamabadi et al., the biggest mortality rate by far, belonged to pedestrians (12). ahvaz city, southeast iran, is located in an accidentprone location, and there are not enough studies regarding traffic accident characteristics in this city. therefore, the present study aimed to evaluate the effective factors in severity of traffic accident-related traumas based on haddon matrix. methods: in the present 1-month cross-sectional study, all traffic accident trauma patients in, who were referred to the emergency department (ed) of imam khomeini and golestan hospitals, ahvaz, iran, during march 2013 were evaluated. the present study was approved by the ethics committee of ahvaz jundishapur university of medical sciences. based on the haddon matrix, effective factors in incidence of traffic accidents were defined in 3 groups of host-, agent-, and environment-related (table 1). the severity of injury was calculated using injury severity score (iss). traumas with a score of 1-9 were categorized as mild, 10-15 as moderate, 16-25 as severe, and over 25 as critical (13). patients were included from equal morning and night shifts (20 patients from each shift on average). demographic data of the patients and data regarding risk factors based on haddon matrix were extracted and recorded by 3 trained emergency medicine residents using the police and medical files as well as asking the patient or their relatives. patients with missing data were excluded from the study. after gathering the data, they were recorded and analyzed using spss version 20. descriptive indices were described using frequency, percentage, and mean ± standard deviation, and qualitative ones were compared using chi square test. p < 0.05 was considered as significance level. to reserve patient rights, all the researchers adhered to the principles of helsinki declaration and kept patient information confidential. results: 700 traffic accident trauma patients, with the mean age of 29.66 ± 12.64 years (range: 3 82) were admitted to the afore-mentioned eds during 1 month (92.4% male). trauma mechanism was pedestrian-car in 308 (44%) of the cases and car-motorcycle in 175 (25%). 610 (87.1%) cases were urban accidents and 371 (53%) occurred in the time between 2 pm and 8 pm. violation of speed limit was the most common violation with 570 (81.4%) cases, followed by violation of right-of-way in 57 (8.1%) patients. all the drivers used seat belts (100%), while only 84.23% of the motorcycle riders used helmets. table 2 shows the distribution of traffic accident injuries based on age; sex; type, time, and location of accident; severity of injury; and type of safety tools and moving violation. 59.9% of the severe and critical injuries had occurred in road accidents, while 61.3% of traffic ones were mild to moderate (p < 0.001). 14 (70%) of the accidents that had occurred in locations without proper safety, had led to severe to critical injuries. while in safe locations, 405 (59.5%) cases had mild to moderate injuries (p = 0.013). undertaking, crossing over a center divider, violation of right-of-way, and violating speed limit were the cause of 65.51%, 27.27%, 22.8%, and 19.28% of the critical injuries, respectively (p < 0.001). the most common mechanisms of trauma for critical injuries were rollover (72.5%), motorcycle-pedestrian (23.8%), and car-motorcycle (13.14%) accidents (p < 0.001). table 3 summarizes the effects of environment-, host-, and agent-related factors based on collision severity. discussion: results of the present study showed that the severity of injuries cause by traffic accidents is in correlation with factors such as age, accident location, type of accident, time of accident, and type of moving violation. in addition, mean injury severity in this study was estimated to be moderate to severe. most of the injured were young men under 40 years old, which was similar to a study by kumar et al. and some other studies (10, 11). in other table 1: effective risk factors in occurrence of accident based on the haddon matrix category risk factors host age, using safety tools (helmet in motorcycle riders, seat belt in drivers) and moving violation (violation of speed limit, undertaking, crossing over a center divider, violation of rightof-way) agent accident type (pedestrian car , pedestrian motorcycle, 2 motorcycles, 2 cars, falling down) environment safety of the accident location (pedestrian line or footbridge, traffic light, guard rail, proper road construction, proper lighting), weather conditions at the location (time of accident), place of accident (traffic or road) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com masoumi et al 80 countries, even western ones, men are far more susceptible to injury caused by accidents. in this study, most patients were injured in car-pedestrian accidents, which is in line with another study that reported vehicles hitting pedestrians as the most common cause of injury (14). yet, some studies have introduced motorcycle accidents as the most common cause of trauma (15, 16). although car-motorcycle accidents had a high frequency in this study, car-pedestrian accidents were the most common. this emphasizes the importance of educating pedestrians, either in schools or through the media, to decrease pedestrian mortality, especially among children and teenagers. the results of the study carried out on 343082 accident cases in iran in 2006 showed that, 276000 were injured in traffic accidents. 56% of the accidents were caused by the collision of 2 vehicles, 64.5% happened due to violation of the traffic rules, and 34% occurred at the time of sunrise or sunset (3). most of the accidents in the present study had occurred in the evening (2 pm to 8 pm), which was in line with the 2006 study regarding frequency of accidents at sunrise and sunset (4). in the present study, most common moving violation was speed violation. injury severity in traffic and road accidents was significantly different, which is in line with the results of a study by wang et al. that evaluated 568 cases in 1 year. they expressed that age over 45 years, migrated population, weather conditions, type of accident, and road conditions significantly correlated with severe accident injuries (11). in this study, injury severity significantly correlated with type of accident, and critical injuries were mostly due to rollover, which is in line with the wong et al. study (11). unsafe environment of the location of accident also showed a significant correlation with trauma severity, similar to the results of wang et al. (11). analyses showed that type of moving violation and severity of injury significantly correlated and violation of speed resulted in more severe injuries. in addition, severity of injury varied significantly among different age groups. the most severe injuries belonged to people in the > 50 age group. this was in contrast with the results of a study done in china that reported age under 45 correlated with injury severity. injury severity was significantly higher in midnight accidents (8 pm to 8 am). apparently, planning to eliminate or decrease environment-, host-, and agent-related risk factors leading to severe and critical traumas in the first phase, and mild and moderate ones later, can considerably decrease financial and health-related costs of traffic accidents. educating the society using educational programs and encouragement/punishment, improving road conditions and eliminating its accident hot zones, revising the maximum age allowed for driving, planning special traffic rules for motorcycle riders and reinforcing limitations, and controlling traffic in accident-prone times (2 pm – 8 pm) can be helpful in this regard. the short duration of the study and small sample size are among the limitations of this study. it is recommended to design more general and national studies with larger sample size to be able to identify the correlations of these factors more accurately and decrease traffic accidents and consequently injuries resulting from them. conclusion: based on the results of the present study, the most important effective factors in severity of traffic accident-related traumas were age over 50, not using safety tools, and undertaking among host-related factors; insufficient table 2: baseline characteristics of patients characteristics n (%) age group (years) < 16 37 (5.3) 17-30 387 (55.3) 30-40 154 (22) 40-50 66 (9.4) 50-65 39 (5.6) ≥ 65 17 (2.4) sex male 647 (92.4) female 53 (7.6) type of accident car-pedestrian 308 (44) car-motorcycle 175 (25) rollover 80 (11.4) car-car 48 (6.9) motorcycle-motorcycle 47 (6.7) motorcycle-pedestrian 42 (6) location traffic accident 610 (87.1) road accident 90 (12.9) time of accident (hour) 8 am – 2 pm 245 (35) 2 pm – 8 pm 371 (53) 8 pm – 8 am 84 (12) injury score* 1 9 (mild) 197 (28.1) 10 15 (moderate) 214 (30.6) 16 25 (severe) 137 (19.6) > 25 (critical) 152 (21.7) using safety tools seat belt 128 (100) helmet 187 (84.23) moving violation speed limit violation 570 (81.4) violation of right-of-way 57 (8.1) crossing over a center divider 44 (6.3) undertaking 29 (4.1) * based on injury severity score (iss). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 81 emergency (2016); 4 (2): 78-82 environment safety, road accidents and time between 2 pm and 8 pm among environmental factors; and finally, rollover, car-pedestrian, and motorcycle-pedestrian accidents among the agent factors. acknowledgments: we would like to acknowledge all the staff of emergency ward of imam khomeini and golestan hospitals, tehran, iran. conflict of interest: we declare that the authors of this article have no competing interests. funding support: none. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. hoyt db, coimbra r, potenza b. management of acute trauma. sabiston textbook of surgery. 4 ed. philadelphia: saunders; 2004. p. 483-532. 2. sharma b. road traffic injuries: a major global public health crisis. public health. 2008;122(12):1399-406. 3. eid ho, barss p, adam sh, et al. factors affecting anatomical region of injury, severity, and mortality for road trauma in a table 3: the effects of haddon matrix factors on injury severity accident characteristics injury severity based on iss* (%) p mild moderate severe critical e n v ir o n m e n t location safety negative 2 (10) 4 (20) 4 (20) 10 (50) 0.013 positive 195 (28.7) 210 (30.9) 133 (19.5) 142 (20.9) location urban road 15 (16.7) 22 (24.4) 19 (21.1) 34 (37.8) 0.001 inter-city road 182 (29.8) 192 (31.5) 118 (19.3) 118 (19.3) time (hour) 8 am – 2 pm 81 (33.1) 78 (31.8) 40(16.3) 46 (18.8) 0.001 2 pm – 8 pm 100 (27) 124 (33.4) 84 (22.6) 63 (17) 8 pm – 8 am 16 (19) 12 (14.3) 13 (15.5) 43 (51.2) h o s t age (year) 0.036 < 16 12 (32.4) 14 (37.8) 6 (16.2) 5 (13.5) 17-30 119 (30.7) 115 (29.7) 74 (19.1) 79 (20.4) 30-40 39 (25.3) 52 (33.8) 33 (21.4) 30 (19.5) 40-50 14 (21.2) 23 (34.8) 7 (10.6) 22 (33.3) 50-65 7 (17.9) 9 (23.1) 13 (33.3) 10 (25.6) ≥ 65 6 (35.3) 1(5.9) 4 (23.5) 6 (35.3) using safety tools seat belt no 0 0 0 0 0.001 yes 30 (23.4) 24 (18.7) 10 (7.8) 64 (50) helmet no 0 10 (28.6) 19 (54.3) 6 (17.1) yes 35 (19.5) 68 (38) 61 (34.1) 23 (12.8) moving violation speed limit 160 (28.6) 186 (33.2) 116 (21.7) 108 (19.3) 0.001 undertaking 2 (6.9) 6 (20.7) 2 (6.9) 19 (65.5) crossing** 18 (40.9) 11 (25) 3 (6.8) 12 (27.3) right-of-way 17 (29.8) 11 (19.3) 16 (28.1) 13 (22.8) a g e n t mechanism of injury car-pedestrian 121 (39.3) 102 (33.1) 46 (14.9) 39 (12.7) 0.001 car-motorcycle 35 (20) 61 (34.8) 56 (32) 23 (13.1) 2 motorcycles 0 17 (36.2) 24 (51.1) 6 (12.8) 2 cars 25 (52.1) 13 (27.1) 4 (8.3) 6 (1.2) motor-pedestrian 11 (26.2) 10 (23.8) 11 (26.2) 10 (23.8) rollover 5 (6.2) 11 (13.7) 6 (7.5) 58 (72.5) * iss: injury severity score, ** crossing over a center divider. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com masoumi et al 82 high-income developing country: lessons for prevention. injury. 2009;40(7):703-7. 4. majdzadeh r, khalagi k, naraghi k, motevalian a, eshraghian mr. determinants of traffic injuries in drivers and motorcyclists involved in an accident. accid anal prev. 2008;40(1):17-23. 5. åstrøm an, moshiro c, hemed y, heuch i, kvåle g. perceived susceptibility to and perceived causes of road traffic injuries in an urban and rural area of tanzania. accid anal prev. 2006;38(1):54-62. 6. bidgoli hh, bogg l, hasselberg m. pre-hospital trauma care resources for road traffic injuries in a middle-income country—a province based study on need and access in iran. injury. 2011;42(9):879-84. 7. saadat s, yousefifard m, asady h, jafari am, fayaz m, hosseini m. the most important causes of death in iranian population; a retrospective cohort study. emergency. 2014;3(1):16-21. 8. peden m. world report on road traffic injury prevention. world health organization geneva; 2004. 9. christoffel t, gallagher ss. injury prevention and public health: practical knowledge, skills, and strategies: jones & bartlett learning; 2006. p. 10. kumar ps, srinivasan k. to study the socio demographic profile of road traffic accident victims in district hospital, karimnagar. int j res dev health august. 2013;1(3):136-40. 11. wang s-m, dalal k. road traffic injuries in shanghai, china. healthmed. 2012;6(1):74-80. 12. hatamabadi h, vafaee r, haddadi m, abdalvand a, esnaashari h, soori h. epidemiologic study of road traffic injuries by road user type characteristics and road environment in irán: a community-based approach. traffic inj prev. 2012;13(1):61-4. 13. baker sp, o'neill b, haddon jr w, long wb. the injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. j trauma. 1974;14(3):187-96. 14. taghipour h, panahi f, khoshmohabat h, hojati firoozabadi n, moharamzad y, abbasi a. causes and severity of fatal injuries in autopsies of victims of fatal traffic accidents. j shahid sadoughi uni med sci. 2010;17(5):358-64. [persian]. 15. fakharian e, taghaddosi m, masoud sa. epidemiology of head trauma in kashan. kaums j. 2003;7(1):64-70. [persian]. 16. javouhey e, guerin a-c, chiron m. incidence and risk factors of severe traumatic brain injury resulting from road accidents: a population-based study. accid anal prev. 2006;38(2):225-33. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 97 emergency (2016); 4 (2): 97-100 brief report sudden death following exercise; a case series fares najari1*, alimohammad alimohammadi2, parisa ghodrati3 1faculty member of shahid beheshti university of medical science, tehran, iran. 2center of forensic medicine researches, forensic medicine of iran. 3forensic medicine department, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: fares najari; department of forensic medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tal: 00989123195140, email: fares.hospital@yahoo.com received: jun 2015; accepted: august 2015 abstract introduction: natural and unexpected death that happens within less than one hour of first symptom occurrence is called sudden death. cardiovascular diseases are the main known reason of sudden death and more than 75% of sudden deaths in athletes are assigned to it. here we reported the autopsy results of all cases with sudden death following exercise that were referred to forensic center of tehran, iran, from 2009 to 2014. methods: in this cross sectional study all subjects who were registered to forensic medicine center of tehran, iran, from 2009 to 2014, as a case of sudden death following exercise were evaluated. demographic data and medical history as well as autopsy and toxicology findings were retrospectively gathered using profiles of the deceased. results were reported using descriptive analysis. results: 14 cases were registered as sudden death following exercise in forensic medicine profiles during the study period. exploring the files of the mentioned deceased, revealed five non-compatible cases in this regard. finally, 9 eligible cases were enrolled (88.9% male). the mean age of the deceased was 28.66 ± 10.86 years (range: 7 – 40). toxicological tests were available for 7 cases, one of which was positive for tramadol. sudden death following football was reported most frequently (44.4%). only 3 (33.3%) cases had herald signs such as chest pain, syncope, or loss of consciousness. 1 case (11.11%) had a positive history of sudden death in relatives. conclusion: although most sudden death victims are asymptomatic until the event, all those who suffer from symptoms such as chest pain, shortness of breath, dizziness, fatigue and irregular heart rate during physical activities, should be screened regarding common probable causes of sudden death. keywords: sudden death; exercise; autopsy; forensic medicine cite this article as: najari f, alimohammadi am, ghodrati p. sudden death following exercise; a case series. emergency. 2016; 4(2):97-100. introduction: atural and unexpected death that happens within less than one hour of first symptom occurrence is called sudden death (1-4). sudden death is more common among men and the black race (5, 6). in a systematic review based on data related to 1980-2007, annual incidence of sudden cardiac death (scd) in the united states varied between 180000 and 450000 (7). in some other studies, scd rate range was reported 50-100 per 100000 of general population in countries such as netherlands, ireland, and china (8). cardiovascular diseases are among the main known causes of sudden death. interestingly, in about 25% of patients who die of coronary artery atherosclerosis, the first sign is sudden death. after coronary artery diseases, cardiomyopathies including hypertrophic and dilated types are among the second cardiac causes of sudden death (1). dysfunctions of the heart valves, especially aortic stenosis, are considered as other underlying cardiac causes of sudden death (9). hypertrophic cardiomyopathy is the most common cause of sudden death in people under thirty years of age (10). most patients with hypertrophic cardiomyopathy are asymptomatic and death can occur at rest or with mild physical activity, however, sudden death often occurs during intense physical activity (10, 11). in many cases, hypertrophic cardiomyopathy is the only autopsy finding in young victims of sudden death and is the most common reason of sudden death during exercise (12). drug abuse (such as stimulants, anabolic steroids, opioids, and etc.), bronchoconstriction, heat stroke, and drowning can be mentioned as non-cardiac causes of sudden death in athletes but cardiac causes are more important (9, 13-15). n this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com najari et al 98 about 69% of sudden deaths in general population are attributed to cardiovascular diseases, while more than 75% of sudden deaths in athletes are assigned to it (13, 16). to emphasize the importance of this topic, here we review the forensic reports of all cases of sudden death following exercise, referred to forensic medicine center of tehran, iran, from 2009 to 2014. methods: in this cross sectional study, all subjects who were registered to forensic medicine center of tehran, iran, from 2009 to 2014, as a case of sudden death following exercise were evaluated. demographic data (age, sex) and medical history as well as autopsy and toxicology findings were gathered using deceased profiles, retrospectively. cause of death was reported based on final conclusion of forensic medicine specialists. there were not any age or sex limitations. the protocol of study was approved by the ethics committee of shahid beheshti university of medical sciences. authors adhered to helsinki declarations during the study period. results were reported using descriptive analysis. table 1: baseline characteristics and autopsy findings of the studied deceased age* sex activity history toxicology autopsy conclusion 1 31 male football sudden drop one year ago 2 weeks intermittent chest pain father sudden death negative aortic stenosis left ventricular hypertrophy aortic stenosis and hypertrophic cardiomyopathy 2 35 female swimming negative na lung congestion liver stiffness hepatocyte necrosis coronary atherosclerosis acute coronary syndrome 3 7 male gymnastics negative negative lung congestion brain edema liver stiffness plural effusion ascites acute cardiopulmonary syndrome 4 40 male football transient chest pain during last year negative congested cranial vessels edematous lungs enlarged heart aortic entrance plaques ischemic cardiovascular disease 5 17 male football negative negative congested spleen coronary atherosclerosis myocarditis hepatocyte necrosis acute cardiac syndrome 6 36 male fitness negative na brain congestion emphysematous lung coronary atherosclerosis ischemic heart disease on coronary atherosclerosis 7 24 male football congenital heart disease cardiac surgery tramadol emphysematous lung cardiac hypertrophy aortic valve calcification aortic valve dilatation dilated ventricles acute heart syndrome due to advance heart disease 8 30 male lifting negative negative brain edema subarachnoid hemorrhage edematous lung cardiac hypertrophy fatty liver changes diffuse cerebral hemorrhage 9 38 male swimming negative negative stomach erosion brain vascular congestion lung congestion fatty liver coronary atherosclerosis changes cardiomyocytes fibrosis acute myocardial syndrome *: year; na: not available. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 99 emergency (2016); 4 (2): 97-100 results: 14 cases were registered as sudden death following exercise in forensic medicine profiles during the study period. exploring the files of the mentioned deceased, revealed five non-compatible cases in this regard. the cause of death was homicide in one case (4.5 years old boy), drowning in another (38 year-old female), and myocardial infarction in the last three cases (all above 40 years old). finally, 9 eligible cases were enrolled (88.9% male). the mean age of the deceased was 28.66 ± 10.86 years (range: 7 – 40). toxicological tests were available for 7 cases, which was positive for tramadol in one case. table 1 summarizes the baseline characteristics, pathology and autopsy findings of the deceased. sudden death following football was reported most frequently (44.4%). only 3 (33.3%) cases had herald signs such as chest pain, syncope, or loss of consciousness. 1 case (11.11%) had positive history of sudden death among relatives. discussion: in recent years, concerns and interests of the people and physicians regarding causes of sudden death in athletes have impressively increased. causes of scd in athletes can be divided into two groups according to age. congenital heart defects, hypertrophic cardiomyopathy, coronary artery disease, and myocarditis are among the most prevalent causes of scd in patients under 35 years of age. on the other hand, acquired coronary artery disease is a common cause of sudden death in over 35 year old population (13-16). sudden death can occur in approximately all types of sports but it has been more frequently reported in sports like football and basketball. in the current study, most deaths had occurred after football and swimming. in some studies, the risk of sudden death following exercise in men has been reported to be 5 times more than women and the findings of this study has demonstrated this matter (16). two new studies have confirmed the efficacy of screening before participation in matches. baggish and colleagues studied cardiovascular screening effects with and without electrocardiography (ecg) in the 510 collegiate athletes of united states. involving ecg, compared to its non-use in the screening, increased identification of cardiomyopathy cases, sensitivity of screening program (from 45.5% to 90.9%), and negative predictive value (from 98.7% to 99.8 %) (17). mild symptoms such as slight chest pain and other symptoms that indicate heart problems such as exertional dyspnea should be seriously regarded and taught to all people, so that similar cases can be prevented. the authors of this article recommend asking the necessary questions listed in table 2 for primary screening of at risk patients for sudden death following exercise. in case of any positive answer to the mentioned questions, the participant should be referred for further medical investigations. limitation: it should be mentioned that not all cases of sudden death are referred to forensic medicine center for autopsy, especially in cases of clear diagnosis such as acute myocardial infarction or brain insults (hemorrhagic, ischemic, etc.). conclusion: although most sudden death victims are asymptomatic until the event, all those who suffer from symptoms such as chest pain, shortness of breath, dizziness, fatigue and irregular heart rate during physical activities, should be screened regarding common probable causes of sudden death. acknowledgments: we would like to express our special thanks to the forensic center of tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: table 2: necessary questions to figure out warning signs of sudden death in athletes 1 do you have a positive family history of sudden death or not? 2 is there any family history of congenital heart disease or not? 3 is there any history of chest pain after activity or not? 4 do you experience dizziness or loss of consciousness for a moment following activities or not? 5 is there a history of dyspnea with physical activity or not? 6 do you have a history of severe heart palpitations during physical activity or not? 7 is there a history of connective tissue diseases such as marfan syndrome in the family or not? 8 have you become ill during exercise or after it? 9 when you exercise, do you get tired more quickly than your friends? 10 do you have high blood pressure? 11 has any doctor ever prohibited you from participating in sports due to heart reasons? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com najari et al 100 1. saukko p, knight b. knight's forensic pathology: crc press; 2004. 2. naneix a-l, périer m-c, beganton f, jouven x, de la grandmaison gl. sudden adult death: an autopsy series of 534 cases with gender and control comparison. journal of forensic and legal medicine. 2015;32:10-5. 3. yousuf o, chrispin j, tomaselli gf, berger rd. clinical management and prevention of sudden cardiac death. circulation research. 2015;116(12):2020-40. 4. van der werf c, van langen im, wilde aa. sudden death in the young what do we know about it and how to prevent? circulation: arrhythmia and electrophysiology. 2010;3(1):96104. 5. kannel wb, cupples la, d'agostino rb. sudden death risk in overt coronary heart disease: the framingham study. american heart journal. 1987;113(3):799-804. 6. kuller lh. sudden death—definition and epidemiologic considerations. progress in cardiovascular diseases. 1980;23(1):1-12. 7. kong mh, fonarow gc, peterson ed, et al. systematic review of the incidence of sudden cardiac death in the united states. journal of the american college of cardiology. 2011;57(7):794801. 8. deo r, albert cm. epidemiology and genetics of sudden cardiac death. circulation. 2012;125(4):620-37. 9. harris km, tung m, haas ts, maron bj. under-recognition of aortic and aortic valve disease and the risk for sudden death in competitive athletes. journal of the american college of cardiology. 2015;65(8):860-2. 10. sovari aa, kocheril ag, baas as. sudden cardiac death. medscape reference. 2011. 11. kuriachan vp, sumner gl, mitchell lb. sudden cardiac death. current problems in cardiology. 2015;40(4):133-200. 12. maron bj, casey sa, chan rh, garberich rf, rowin ej, maron ms. independent assessment of the european society of cardiology sudden death risk model for hypertrophic cardiomyopathy. the american journal of cardiology. 2015. 13. corrado d, baritussio a, siciliano m, et al. sudden death in athletes. electrical diseases of the heart: springer; 2013. p. 363-80. 14. futterman lg, myerburg r. sudden death in athletes. sports medicine. 1998;26(5):335-50. 15. futterman l, lemberg l. sudden death in athletes. american journal of critical care. 1995;4(3):239-43. 16. patel v, elliott p. sudden death in athletes. clinical medicine. 2012;12(3):253-6. 17. wheeler mt, heidenreich pa, froelicher vf, hlatky ma, ashley ea. cost-effectiveness of preparticipation screening for prevention of sudden cardiac death in young athletes. annals of internal medicine. 2010;152(5):276-86. emergency. 2016; 4 (2): 111-113 ev i d e n c e ba s e me d i c i n e evidence based emergency medicine; part 5 receiver operating curve and area under the curve saeed safari1, alireza baratloo1, mohamed elfil2∗, ahmed negida3. 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. faculty of medicine, alexandria university, egypt. 3. faculty of medicine, zagazig university, egypt. received: march 2016; accepted: april 2016 cite this article as: safari s, baratloo a, elfil m, negida a. evidence based emergency medicine; part 5 receiver operating curve and area under the curve . emergency. 2016; 4(2):111-113. 1. abstract multiple diagnostic tools are used by emergency physicians, every day. in addition, new tools are evaluated to obtain more accurate methods and reduce time or cost of conventional ones. in the previous parts of this educational series, we described diagnostic performance characteristics of diagnostic tests including sensitivity, specificity, positive and negative predictive values, and likelihood ratios. the receiver operating characteristics (roc) curve is a graphical presentation of screening characteristics. roc curve is used to determine the best cutoff point and compare two or more tests or observers by measuring the area under the curve (auc). in this part of our educational series, we explain roc curve and two methods to determine the best cutoff value. 2. definition roc curve is a graphical presentation, which is created by plotting the true positive rate (sensitivity) against the false positive rate (1-specificity) at various threshold settings (1,2). 3. the area under roc curve it is known that when sensitivity increases, false positive rate also increases. therefore, roc curve allows us to check sensitivity and false positive rate (1specificity) at any point on the curve. the area under the curve is a measurement of the overall quality of the diagnostic test. tests with the same auc show the same overall diagnostic performance, but not the same sensitivity and specificity. auc is interpreted as ∗corresponding author: mohamed elfil; faculty of medicine, alexandria university, egypt. address: 601 delma plaza, smouha, alexandria, egypt.tel: +201285818091. e-mail: m_elfil13@alexmed.edu.eg. figure 1: roc curve for a test with a sensitivity and specificity of 100% (a). roc curve for a useless test (b). the probability that a random person with the disease has a higher test measurement than a random person who is healthy. accuracy of a test is measured by the auc, which can be calculated by many statistical software (1,2). based on a rough classifying system, auc can be interpreted as follows: 90 -100 = excellent; 80 90 = good; 70 80 = fair; 60 70 = poor; 50 60 = fail. in figure 1, the line (a) represents the roc for an ideal diagnostic test. this curve represents a sensitivity and specificity of 100%. the auc for this line is equal to 100, which is not common in practice. on the other hand, the diagonal line (b) represents roc for a useless diagnostic test. this can be explained by noting that the true positive rate of the diagnosthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m_elfil13@alexmed.edu.eg s. safari et al. 112 figure 2: roc curve of triss system figure 3: roc curve of apache iii system tic test is equal to the false positive rate at any cutoff point. the auc for this line is equal to 45, which is why such test is of no real value. 4. determining the best cutoff point on roc curve there are two methods to choose the best cutoff point. 5. the first method it is known that the upper left corner of the graph represents the point with 100% sensitivity and 100% specificity. therefore, the point on the curve that gives the highest sensitivity and the highest specificity will be the nearest point to the upper left corner of the graph. to determine the nearest point, we should measure the distance between each point and the upper left corner and choose the nearest point as the best cutoff point. to measure the distance of each point from the upper left corner, we can use the following equation: distance = √ [(1 − se n si t i v i t y )2 + (1 − s p e c i f i c i t y )2] the point with the shortest distance should be chosen as the best cutoff point. 6. the second method the second method is called youden index where we aim at maximizing the gap between true positive rate (represented as: sensitivity) and false positive rate (represented as 1specificity). in this method, we calculate (sensitivity + specificity) for all points and youden index is the point where the sum of sensitivity and specificity is the highest. 7. example in the recently published study by mazandarani and colleagues (4), they compared the ability of trauma injury severity score (triss) and acute physiology and chronic health evaluation (apache) iii to predict mortality of intensive care unit admitted trauma patients. roc curves for the methods are shown in figure 2 and 3. figure 2 shows the roc curve for triss; we notice that the curve is nearest to the upper left corner in the cutoff point (13.2) and therefore, the maximum sensitivity and specificity are achieved at this point (sensitivity = 76.52%; specificity = 95.65%). figure 3 shows the roc curve for apache iii; we notice that the curve is nearest to the upper left corner in the cutoff point (51) and therefore, maximum sensitivity and specificity are achieved at this point (sensitivity = 73.91%; specificity = 78.26%). 8. notes * this method might yield more than one cutoff point and therefore choosing between them is challenging. * this method gives sensitivity and specificity equal priority in the diagnostic test; sometimes the cost of screening is high and the disease is rare, in these conditions, sensitivity and specificity are not given the same priority when determining the best cutoff point. the method of integrating the cost of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 113 emergency. 2016; 4 (2): 111-113 screening and prevalence of the disease with sensitivity and specificity while determining the best cutoff is rarely used in medical literature. references 1. kumar r, indrayan a. receiver operating characteristic (roc) curve for medical researchers. indian pediatr. 2011;48(4):277–87. 2. altman dg, bland jm. diagnostic tests 3: receiver operating characteristic plots. bmj. 1994;309(6948):188. 3. akobeng ak. understanding diagnostic tests 3: receiver operating characteristic curves. acta paediatr. 2007;96(5):644–7. 4. acute physiology and chronic health evaluation (apache) iii score compared to trauma-injury severity score (triss) in predicting mortality of trauma patients. 2015;3:1–4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com abstract definition the area under roc curve determining the best cutoff point on roc curve the first method the second method example notes references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 25 emergency (2016); 4 (1): 25-28 original research true vertigo patients in emergency department; an epidemiologic study ali shahrami, mehdi norouzi*, hamid kariman, hamid reza hatamabadi, ali arhami dolatabadi emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mehdi norouzi; department of emergency medicine, imam hossein hospital, shahid madani avenue,tehran, iran. tel: +989123123138; email: m58.norouzi@gmail.com received: may 2015; accepted: june 2015 abstract introduction: vertigo prevalence is estimated to be 1.8% among young adults and more than 30% in the elderly. 13-38% of the referrals of patients over 65 years old in america are due to vertigo. vertigo does not increase the risk of mortality but it can affect the patient’s quality of life. therefore, this study was designed to evaluate the epidemiologic characteristics of vertigo patients referred to the emergency department (ed). methods: in this 6-month retrospective cross-sectional study, the profiles of all vertigo patients referred to the ed of imam hossein hospital, tehran, iran, from october 2013 to march 2014 were evaluated. demographic data and baseline characteristics of the patients were recorded and then patients were divided into central and peripheral vertigo. the correlation of history and clinical examination with vertigo type was evaluated and screening performance characteristics of history and clinical examination in differentiating central and peripheral vertigo were determined. results: 379 patients with the mean age of 50.69 ± 11.94 years (minimum 18 and maximum 86) were enrolled (58.13% female). there was no sex difference in vertigo incidence (p = 0.756). a significant correlation existed between older age and increase in frequency of central cases (p < 0.001). no significant difference was detected between the treatment protocols regarding ed length of stay (p = 0.72). there was a significant overlap between the initial diagnosis and the final decision based on imaging and neurologist’s final opinion (p < 0.001). in the end, 361 (95.3%) patients were discharged from ed, while 18 were disposed to the neurology ward. no case of mortality was reported. conclusion: sensitivity and specificity of history and clinical examination in differentiating central and peripheral vertigo were 99 (95% ci: 57-99) and 99 (95% ci: 97-99), respectively. key words: vertigo; epidemiology; mass screening; emergency department cite this article as: shahrami a, norouzi m, kariman h, hatamabadi hr, arhami dolatabadi a. true vertigo patients in emergency department; an epidemiologic study. emergency. 2016;4(1):25-28. introduction: ertigo is an unpleasant symptom of diseases such as labyrinthitis, meniere's disease, migraine, multiple sclerosis, and cervical spine osteoporotic lesions. vertigo prevalence is estimated to be 1.8% among young adults and more than 30% in the elderly (1, 2). its incidence increases with age, 13-38% of the referrals of patients over 65 years old in america are due to vertigo (3-6). usually, vertigo does not increase the risk of mortality but it can affect the patient’s quality of life. the best treatment modality is still a matter of question. currently, various therapeutic strategies such as medication, surgery, rehabilitation, and physical maneuvers are available (7-10). most cases of vertigo are caused by benign and self-restricting diseases. differentiation of central types of vertigo, which require hospitalization and supplementary diagnostic and therapeutic measures, is of great importance. based on above-mentioned, this study was designed to evaluate the epidemiologic characteristics of vertigo patients referred to the emergency department (ed). methods: in this 6-month retrospective cross-sectional study, the profiles of all vertigo patients referred to the ed of imam hossein hospital, tehran, iran, from october 2013 to march 2014 were evaluated. census sampling was used and all the vertigo patients referred to the hospital during this time were included. demographic data and baseline characteristics of the patients including medical history, accompanied symptoms (nausea, hearing loss, tinnitus, headache), services that visited the patient, treatv this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shahrami et al 26 ment strategies, medications, and disposition were recorded using a checklist. patients were then divided into central and peripheral vertigo groups based on the findings of their history and clinical examination such as presence or absence of tinnitus, hearing loss, nystagmus characteristics, signs of sympathetic release, focal neurologic findings, etc. the final decision on the type of vertigo (peripheral or central) was made based on the results of brain imaging or para-clinical findings and the opinion of an expert neurologist. standard indications of brain computed tomography (ct) were considered age over 55 years, abnormal neurologic findings on examination, history of diabetes and hypertension. in addition, brain magnetic resonance imaging (mri) indications were history of multiple sclerosis and abnormal cerebellar tests (heel to shin or finger to nose examination). the ethics committee of shahid beheshti university of medical sciences approved this study. the researchers adhered to the principles of helsinki declaration and confidentiality of patient information over the course of the study. statistical analysis data were statistically analyzed using spss version 21. quantitative variables were reported as mean ± standard deviation and qualitative ones were introduced as frequency and percentage. the correlation of history and clinical examination with vertigo type (central or peripheral) was evaluated and finally screening performance characteristics of history and clinical examination in differentiating central and peripheral vertigo were determined. significance level was considered p < 0.05. results: demographic 492 patients with initial diagnosis of vertigo were referred to the ed over the course of the study, 18 of them were excluded due to lack of access to their profile and 8 due to initial misdiagnosis. the other 379 patients with the mean age of 50.69 ± 11.94 years (minimum 18 and maximum 86) were enrolled (58.13% female). table 1 shows the baseline characteristics of these patients. there was no sex difference in vertigo incidence (p = 0.756). 239 (65.3%) of the participants were in the 4060 years age range. figure 1 displays the age distribution of central and peripheral vertigos. a significant correlation existed between older age and increase in frequency of central cases (p < 0.001). table 2 shows the correlation between the results of history and clinical examination and final decision of central or peripheral vertigo. treatment 71 (18.7%) patients did not respond to the initial medication and needed rescue doses. most used treatment protocols are shown in table 3. among double drug treatments, promethazine + ondansetron, promethazine + metoclopramide, diazepam + ondansetron, and diazepam + metoclopramide most efficiently relieved symptoms, respectively (p < 0.001). in addition, in single drug treatments promethazine was the most efficient, while diazepam and ondansetron were both inefficient in symptom relief (p = 0.84). no significant difference was detected between the treatment protocols regarding ed length of stay (p = 0.72). dix–hallpike diagnostic maneuver was not carried out for any of the patients in ed. diagnostic brain ct showed hemorrhage in only 2 (0.5%) of the patients. neurology service consultation was required for 64 (16.9%) patients, while neurosurgery service consultation was necessary for 2 due to evidence of hemorrhage in brain ct scan (0.5%). based on the history and initial physical examination, 13 (3.4%) patients were diagnosed with central vertigo (all over 40 years old). table 1: baseline characteristic of the studied patients baseline characteristics number (%) sex female 220 (58.13) male 159 (41.86) age (year) under 40 72 (18.99) 40-50 111 (29.28) 50-60 140 (36.93) over 60 56 (14.77) triage level# 4 and 5 87 (17.68) 3 405 (82.13) medical history hypertension 78 (20) diabetes 33 (8.7) seizure 3 (0.7) head trauma 4 (1) multiple sclerosis 1 (0.2) vertigo 28 (7) accompanying symptoms nausea and vomiting 335 (88.39) tinnitus 31 (8.17) headache 14 (3.69) hearing loss 2 (0.52) cerebellar tests normal 366 (96.54) abnormal 13 (3.43) ct scan* with indication 173 (80.09) without indication 43 (19.90) mri** with indication 14 (36.84) without indication 24 (63.16) services visited internal neurology service 68 (17.9) neurosurgery service 2 (0.5) #, base on emergency severity index (esi) triage system.* computed tomography (ct) scan indications: age over 55, abnormal neurologic findings, history of diabetes and hypertension. ** magnetic resonance imaging (mri) indications: abnormal cerebellar tests and history of multiple sclerosis. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 27 emergency (2016); 4 (1): 25-28 there was a significant overlap between the initial diagnosis and the final decision based on imaging and neurologist’s final opinion (p < 0.001). screening performance characteristics of history and clinical examination in differentiation of vertigo with 95% confidence interval are reported in table 4. outcome in the end, 361 (95.3%) patients were discharged from ed, while 18 were disposed to the neurology ward due to persistence of symptom or positive imaging findings. no case of mortality was reported. discussion: the findings of the present study revealed 3.4% central vertigo frequency, 18.7% resistance to the initial treatment modality, 0.5% positive findings of brain imaging, and 4.7% need for hospitalization in true vertigo patients referred to the ed. in previous studies, up to 25% of central causes of vertigo has been reported, which is in contrast with the findings of this study (11). based on the results of the present study, history and initial clinical examination of the patients has high sensitivity and specificity for differentiating central and peripheral vertigo, which is in line with the results of karatas et al. who introduced history and neurological examination along with imaging as keys for differentiation of central and peripheral causes (11). although, the absolute frequency of female patients was higher in this study, no significant correlation was detected between sex and type of vertigo (central or peripheral) as previous studies had also stated (12, 13). frequency of central vertigo increased with age. this was also in line with previous studies such as min yin’s study, which evaluated 2169 patients aged 7-90 years over a 20-year period (12-16). similar to a study by degreli et al. nausea, vomiting, tinnitus, headache, and hearing loss were the most common accompanying symptoms in this order in the present study (12, 13). promethazine + ondansetron (double-drug) and promethazine (single drug) regimens were the most efficient in controlling symptoms in this study. gananca et al. evaluated drug regimens in treating vertigo and showed that they are very effective in improving true vertigo patients’ conditions. they also reported that betahistine is more efficient in treating peripheral vertigo, while betahistine, cinnarizine, and clonazepam are more e ffective for central vertigo (17). in another study betahistine, prescription and epley’s physical maneuver were evaluated and compared regarding treatment of benign positional vertigo. the results showed that epley’s maneuver is more efficient than drug therapy in short-term treatment of benign positional vertigo (15). degreli et al. assessed efficiency of diazepam, diphenhydramine, and dimenhydrinate in treating ed patients with acute vertigo. the results showed that these drugs were equally effective in treating vertigo but diazepam caused less sedation (12). drug treatments did not have a significant effect on benign peripheral vertigo (18). in another study effectiveness of epley’s maneuver in treating benign paroxysmal peripheral vertigo patients was evaluated and symptom relief was seen in 92.5% of the patients (14). since differentiating central vertigo plays a significant role in management of these patients in ed, evaluating the accuracy of history and initial clinical examination is very important. the results of this study indicate the acceptable accuracy of history and initial clinical examination in triage and initial screening of these patients. this will be more important when there is a lack of equipment and resources, and patients need to be table 2: correlation between the results of history and clinical examination and final decision of central or peripheral vertigo variables frequency of vertigo type (%) p value central peripheral nausea and vomiting 4 (1.2) 331 (98.8) < 0.001 hearing loss 0 (0.0) 2 (100.0) 0.93 tinnitus 0 (0.0) 100 (100.0) 0.32 vertigo 0 (0.0) 28 (100.0) 0.36 head trauma 1 (25.0) 3 (75.0) 0. 13 headache 2 (14.3) 12 (85.7) 0.08 seizure 0 (0.0) 3 (100.0) 0.90 diabetes 4 (12.1) 29 (87.9) 0.02 hypertension 8 (10.3) 70 (89.7) < 0.001 figure1: frequency of central and peripheral vertigo based on age groups (p < 0.001). data are presented as frequency in this figure. 16 49 103 136 45 11 6 0 0 1 4 4 2 2 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% age groups (year) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shahrami et al 28 referred to more equipped centers to undergo brain imaging. only 3.4% of the vertigo patients had central causes and 0.5% of them had positive findings in their brain ct scan. 19.9% of the total 216 ct scans done did not have the indications mentioned in methods. out of the 38 mris done, 63.16% were without indication. it seems that paying attention to minimum present clinical indications can broadly reduce the unnecessary expenses and side effects of radiation in patients. the present study was retrospective and done over a short period, which can lead to deficiency in data regarding outcome, final cause of vertigo, and other required data. a clinical survey is recommended to evaluate diagnosis and treatment of vertigo in patients referred to the ed and a standard protocol should be prepared for management of these patients. conclusion: the findings of the present study revealed 3.4% central vertigo frequency, 18.7% resistance to the initial treatment modality, 0.5% positive findings of brain imaging, and 4.7% need for hospitalization in true vertigo patients referred to the ed. history and initial clinical examination showed acceptable accuracy in initial screening of central vertigo. it seems that doing imaging based on the existing indications leads to about 20% and 60% decrease in ct scan and mri orders, respectively. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. sloane pd, coeytaux rr, beck rs, dallara j. dizziness: state of the science. ann intern med. 2001;134(9_part_2):823-32. 2. reid sa, rivett da. manual therapy treatment of cervicogenic dizziness: a systematic review. man ther. 2005;10(1):4-13. 3. sloane p. dizziness in primary care. results from the national ambulatory medical care survey. j fam pract. 1989;29(1):33-8. 4. nakashima k, yokoyama y, shimoyama r, et al. prevalence of neurological disorders in a japanese town. neuroepidemiology. 1996;15(4):208-13. 5. moulin t, sablot d, vidry e, et al. impact of emergency room neurologists on patient management and outcome. eur neurol. 2002;50(4):207-14. 6. kroenke k, spitzer rl, hahn sr, et al. multisomatoform disorder: an alternative to undifferentiated somatoform disorder for the somatizing patient in primary care. arch gen psychiatry. 1997;54(4):352-8. 7. strain g, myers l. hearing and equilibrium. in: reece w, editor. dukes' physiology of domestic animals. 12 ed. united kingdom: cab direct; 2004. p. 852-64. 8. braunwald e, fauci as, kasper dl, et al. faintness, syncope, dizziness, and vertigo. harrison's principles of internal medicine. 1. bahman: mcgraw-hill professional publishing; 2001. p. 111-8. 9. parfitt k, martindale w. the complete drug reference. london: pharmaceutical press; 1999. p. 51. 10. cohen hs, kimball kt. increased independence and decreased vertigo after vestibular rehabilitation. otolaryngol head neck surg. 2003;128(1):60-70. 11. karatas m. central vertigo and dizziness: epidemiology, differential diagnosis, and common causes. neurologist. 2008;14(6):355-64. 12. değerli v, çevik aa, türkçüer i. comparison of intraveneous diazepam, dimenhydrinate and diphenhydramine on patients with acute peripheral vertigo in the emergency department: a randomized, double blind, clinical trial. turk j emerg med. 2007;7(1):10-7. 13. izadi p, yarmohammadi me, afshinmajd s, et al. effect of dimenhydrinate on benign paroxysmal positional vertigo. razi j med sci. 2011;18(86):12-21. 14. dashti-khadivaki g, absalan a, boroumand p. therapeutic effect of epley maneuver on patients with posterior semicircular canal in benign paroxysmal positional vertigo. zahedan j res med sci. 2010;12(2):36-9. [persian]. 15. ebadi h, borgheie a, mali m, talebi m, rabiei mr. comparison between the effectiveness of physical maneauer and medicinal therapy in the treatment of benign paroxysmal positional vertigo. j mazandaran uni med sci. 2007;17(58):18. [persian]. 16. yin m, ishikawa k, wong wh, shibata y. a clinical epidemiological study in 2169 patients with vertigo. auris nasus larynx. 2009;36(1):30-5. 17. gananca mm, caovilla hh, munhoz ms, et al. optimizing the pharmacological component of integrated balance therapy. braz j otorhinolaryngol. 2007;73(1):12-8. 18. nuti d, nati c, passali d. treatment of benign paroxysmal positional vertigo: no need for postmaneuver restrictions. otolaryngol head neck surg. 2000;122(3):440-4. table 3: most common treatment regimens prescribed for patients treatment regimens number (%) promethazine-ondansetron 96 (25.3) promethazine-metoclopramide 71 (18.7) diazepam-ondansetron 83 (21.9) diazepam-metoclopramide 59 (15.6) promethazine 45 (11.9) ondansetron 16 (4.2) diazepam 9 (2.4) table 4: screening performance characteristics of history and clinical examination in differentiating central and peripheral vertigo screening characteristics (95% confidence interval) sensitivity 90 (57-99) specificity 99 (97-99) positive predictive value 76 (49-93) negative predictive value 99 (98-99) positive likelihood ratio 3.3 (1.9-9.4) negative likelihood ratio 0.002 (0.0003-0.01) emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 36 emergency (2014); 2 (1): 36-39 original research the effect of intravenous ketamine in suicidal ideation of emergency department patients parvin kashani1, shiva yousefian1, afshin amini1, kamran heidari1, somaie younesian1, hamid reza hatamabadi1, 2* 1. department of emergency, shahid beheshti university of medical sciences, tehran, iran 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran abstract introduction: suicidal ideation is an emergent problem in the emergency department (ed) that often complicates patient disposition and discharge. it has been shown that ketamine possesses fast acting antidepressant and anti-suicidal effects. this study was conducted to examine the effects of a single intravenous bolus of ketamine on patients with suicidal ideations in ed. methods: forty-nine subjects with suicidal ideations with or without an unsuccessful suicide attempt, received 0.2 mg/kg of ketamine. scale for suicidal ideation (ssi) and montgomery abserg depression-rating scale (madrs) were evaluated before and 40, 80 and 120 minutes after drug intervention. the results were compared using the paired t-test and patients were followed up 10 days after ed admission for remnant suicide ideation. results: ssi (df: 3, 46; f=80.7; p<0.001) and madrs (df: 3, 46; f=87.2; p<0.001) scores significantly dropped after ketamine injection; the ssi score before and after 20, 40, and 80 minutes of ke tamine injection were 23.0±6.7, 16.2±5.2, 14.3±4.3, and 13.6±4.0 respectively. the madrs scores were 38.2±9.3, 25.6±7.1, 22.7±6.3, and 22.1±5.95 at the same time intervals. 25.5% of patients were hospitalized, 63.3% received medications and 12.2% discharged. 6.2% of patients had suicidal ideations ten days after ed disposition. conclusion: it seems that ketamine could not be a good choice for fast reduction of suicidal ideations in ed patients. further studies are needed to determine the optimal dose of ketamine for different patients. key words: ketamine; suicide; suicidal ideation; emergency cite this article as: kashani p, yousefian s, amini a, heidari k, younesian s, hatamabadi hr. the effect of intravenous ketamine in suicidal ideation of emergency department patients. emergency. 2014;2(1):36-9. introduction: 1 uicidal ideation is an emergent condition that demands immediate attention. it has been shown that the time between decision and attempt in patients with suicidal ideations is about ten minutes (1). various therapeutic interventions to decrease suicide risk have been proposed in serious psychiatric disorders for long-term suicide prevention (2, 3). while the recognition of risk factors is very important for preventing suicide, they fail to clarify the timing of a suspected suicidal behavior. it has been shown that subjects with mood disorders are at greater risk of suicide in the first two years after discharge (4). on the other hand it is known that during admission in emergency department (ed), immediately after discharge from ed, and after starting antidepressants are the time points which the subjects are very vulnerable to suicidal ideations (5-9). therefore, it is crucial to quickly intervene and prevent suicidal behavior in such conditions. it has also been shown that 43% of suicides *corresponding author: hamid reza hatamabadi; associate professor of emergeny medicine department, imam hossein educational hospital, shahid madani ave, emam husain sq, tehraniran. tel+98 2173432380 fax: +98 2177557069; email: hhatamabadi@yahoo.com received: 29 january 2014; accepted: 17 february 2014 occur in the first month after discharge (5). this often complicates the disposition discharge of patient in the ed. a patient with significant suicide ideation cannot be safely discharged or admitted to general wards, regardless of the underlying medical condition. different interventions for decreasing the possibility of suicidal risks are effective in long term. for example, lithium, clozapine, and risperidone are used for such a condition in eds (10-12). however, the acute pharmacological management of suicidal risk remains comparatively under investigation (13). considering the crowdedness of the majority of eds, it is often impossible to offer standard care to patients with suicidal ideation. in such settings, use of pharmaceutical interventions can play an important role with a rapid effect on diminishing suicidal ideation. numerous studies have shown the effect of single dose of intravenous (iv) ketamine on reducing depressive symptoms in approximately 70% of major depressive disorder (mdd) patients in 24 hours after infusion (1418). the effects of ketamine on reducing suicidal ideation in severely depressed patients have been supported by preliminary studies (19). furthermore, a recent naturalistic study proved that a low-dose ketamine is s this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 37 kashani et al effective on reducing the suicide ideation in patients refer to the ed (20) and those who have terminal illness(21). considering to other studies, ketamine is a favorable choice for emergency physicians because of many reasons; its rapid effect as an anti-suicidal ideation causes that the patient can be discharged from the ed with early outpatient follow up. this is especially applicable in situations when an on call psychiatrist is not available. therefore, this study was performed to reaffirm the ketamine effect on patients with suicidal ideation in the ed. methods: study design and setting this single-blind clinical trial was done in emergency department of imam hossein hospital from october to september 2012. participation in the study was voluntary and the consent form was obtained from their companions. patients’ files were completed by the emergency physician and the information was kept strictly confidential. this research was confirmed by ethical committee of imam hossein hospital. participants the patients (age over 16 years) were included in the study based on subjective expression of suicidal ideations or recent suicidal actions at the time of admission to the department. subjects were excluded if a diagnosis of alcohol or substance and drug abuse was made in the past three month or if they had received any medication for two weeks before ed admission. intervention a single dose of ketamine hydrochloride infusion (0.2 mg/kg, over one minute) was administered to the selected subjects. this is the lowest dose of ketamine which has been described as effective in diminishing suicide ideation in previous studies (20, 21). patients’ suicidal ideations were assessed by using montgomeryasberg depression rating scale (madrs) and scale for suicidal ideation (ssi). madrs and ssi scales were completed for all of the patients in different times as follow: before injection and 40, 80, 120 minutes after infusion. the patients’ treatment followed standard ed protocols regardless of the study results; the outcome was followed up ten days after admission by a telephone contact. statistical analysis descriptive analyses were performed by statistical software spss version 21.0 and graphs drawn by excel 2013. the ssi≥4 was considered as significant suicidal ideations and ssi<4 without significant suicidal ideations. ssis were compared before and after ketamine injection by paired t-test and repeated measures analysis of variance. the p<0.05 was considered statistically significant. results: forty-nine patients were included in this study. fifty one percent of patients were female (n=25) and 49% were male (n=24). the mean age of patients was 32±10.8 years. thirty-eight percent of patients (n=19) had a history of mental illness (bipolar and major depression), 30% (n=15) previous suicidal ideations, 12 % (n=6) psychiatric hospitalization, and 34% (n=17) self-injury. table 1 shows the mean and sd of patients’ vital signs before and after injection of ketamine. significant decrease was observed in the values of pr (89.8±8.8 vs. 87.8±7.5; p<0.001) and rr (18.5±5.0 vs. 17.4.0±2.0 respectively, p=0.04) ten minutes after ketamine injection. no significant difference was seen in the levels of bp (14.9±2.01 vs. 12.6±1.9; p=0.32) and o2sat before and after ketamine injection (96.4±1.1 vs. 95.1±1.5; p=0.35). mean and standard deviation of ssi scores before injection and at 40, 80 and 120 min after ketamine injection were respectively, 23.0±6.7, 16.2±5.2, 14.3±4.3 and 13.6±4.0. the repeated measures analysis showed that the ssi scores decreased over time significantly. the most significant reduction was seen in the first 40 minutes after injection (p<0.001) but, the score maintained a decreasing trend until 120 minutes (df: 3, 46; f=80.7; p<0.001). mean and standard deviation of madrs rating scales as well indicated a significant reduction in ssi scores at the times after injection (df: 3, 46; f=87.2; p<0.001). madrs rating scales before injection of ketamine was 38.2±9.3 and at the time of 40, 80 and 120 minutes after injection were respectively 25.6±7.1, 22.7±6.3 and 22.1±5.95. once again the highest rate of reduction was at 40 min after the injection (p<0.001). 25.5% of patients (n=12) were hospitalized, 63.3% (n=31) received medication, and 12.2% (n=6) discharged. follow-up 10 days after admission in ed showed that 85.7% of patients (n=44) did not have any suicidal thoughts, 8.2% (n=4) had hospitalized and table 1: vital signs measures before and after ketamine infusion  vital signs time of injection p before after 10 minute pulse rate 89.8±8.8 87.8±7.5 <0.001 respiratory rate 18.5±5.0 17.4±2.0 0.04 blood pressure (systolic/diastolic) 12.6/8.1 12.6/8.2 0.32 o2 saturation 96.4±1.1 95.1±1.5 0.35 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 38 emergency (2014); 2 (1): 36-39 6.1% (n=3) still had suicidal thoughts. discussion: suicide is one of the leading causes of death among young people especially those who have psychiatric disorders. in the past decade, many efforts have been done to prevent suicide attempts that the most important one was evaluating the risk factors of suicide and ways to prevent this problem (22). suicidal ideation is a medical emergency that requires immediate attention and treatment. unfortunately, therapeutics used now for the rapid decrease in suicidal thoughts is often followed up with unpleasant consequences (23). in this study, the effect of ketamine was evaluated on 49 patients admitted in ed with suicidal ideations and actions. although suicidal ideation did not remove after ketamine injection, evaluation at 40, 80 and 120 min after infusion showed a significant reduction in ssi and madrs scores (figure 1 and 2). previous studies have assessed the effect of ketamine infusion in patients with treatment-resistant depressive disorder and demonstrated rapid beneficial effects on suicidal ideation (18, 19). the results like previous studies show that ketamine is effective in reducing suicidal ideations. yet in our study, the ssi score 40 minutes after the injection of ketamine dropped from 23±6 to 16±5, which although is significant, still above the previously set limit of 4. this might be due to the lower dose of ketamine used in our study compared to prior ones (0.5mg/kg) (19). it means that injection of 0.2mg/kg to patients was unable to eliminate suicidal ideation. a significant reduction was observed in the amount of rr and pr but all of the indices remained in normal limits and no danger threatened patients after injection of ketamine. the follow up of patients after ten days showed that some of them had still suicidal ideations (6.1%). this may reflect a shorter time of action for ketamine at the low dose of ketamine infusion (0.2 mg/kg) used in this study. therefore, if such a dose were used, adjunct treatments or repeated dose maybe also needed. it is clear that the results of current studies should be interpreted with more caution due to the small size of the population. the findings of this study showed that ketamine, as a modulating of glutaminergic system, could not be a good candidate for the quick treatment of suicidal ideations in the ed. however, further studies should be done to confirm the findings of this and previous studies; so that the optimal dose of ketamine for different patients and its lasting impact could be determined. limitations the main limitation of present study is the small sample size. another limitation of this study is the lack of a control group. however, because ketamine does not have any effect on suicidal ideations, this limitation did not affect the findings. conclusion: it seems that ketamine could not be a good choice for fast decrease of suicidal ideations in ed patients. further studies are needed to determine the optimal dose of ketamine for different patients. acknowledgments: we would like to thanks from emergency ward staffs of shohadaye hafte tir hospital. conflict of interest: none funding support: none authors’ contributions: parvin kashani and hamid reza hatamabadi designed the study. shiva yousefian and somaie younesian participated in data gathering. kamran heidari analized the figure 1: scale for suicidal ideation (ssi) scores before and after ketamine infusion.  figure 2: montgomery-abserg depression rating scale (mards) scores before and after ketamine infusion.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 39 kashani et al data. afshin amini followed the patients and wrote the first draft of article. all authors approved the final version of manuscript. references: 1. deisenhammer ea, strauss r, kemmler g, hinterhuber h, weiss em. the duration of the suicidal process: how much time is left for intervention between consideration and accomplishment of a suicide attempt? j clin psychiatry. 2009; 70(1):19-24. 2. linehan mm, comtois ka, murray am, et al. two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder. arch gen psychiatry. 2006;63(7):757-66. 3. brown gk, ten have t, henriques gr, xie sx, hollander je, beck at. cognitive therapy for the prevention of suicide attempts: a randomized controlled trial. jama. 2005;294(5): 563-70. 4. gausset m, casadebaig f, guillaud-bataille j, quemada n, terra j. [mortality of mentally ill patients. review of the literature]. l'encephale. 1991;18(1):93-100. 5. hunt im, kapur n, webb r, et al. suicide in recently discharged psychiatric patients: a case-control study. psychol med. 2009;39(3):443-9. 6. janofsky js. reducing inpatient suicide risk: using human factors analysis to improve observation practices. j am acad psychiatry law. 2009;37(1):15-24. 7. mills pd, derosier jm, ballot ba, shepherd m, bagian jp. inpatient suicide and suicide attempts in veterans affairs hospitals. jt comm j qual patient saf. 2008;34(8):482-8. 8. yeager kr, saveanu r, roberts ar, et al. measured response to identified suicide risk and violence: what you need to know about psychiatric patient safety. brief treat crisis interv. 2005;5(2):121-8. 9. jick h, kaye ja, jick ss. antidepressants and the risk of suicidal behaviors. jama. 2004;292(3):338-43. 10. baldessarini rj, tondo l, davis p, pompili m, goodwin fk, hennen j. decreased risk of suicides and attempts during long‐term lithium treatment: a meta‐analytic review. bipolar disord. 2006;8:625-39. 11. meltzer hy, alphs l, green ai, et al. clozapine treatment for suicidality in schizophrenia: international suicide prevention trial (intersept). arch gen psychiatry. 2003;60(1):82-91. 12. reeves h, batra s, may rs, zhang r, dahl dc, li x. efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. j clin psychiatry. 2008;69(8):1228-36. 13. ernst cl, goldberg jf. antisuicide properties of psychotropic drugs: a critical review. harv rev psychiatry. 2004;12(1): 14-41. 14. zarate ca, singh jb, carlson pj, et al. a randomized trial of an n-methyl-d-aspartate antagonist in treatment-resistant major depression. arch gen psychiatry. 2006;63(8):856-64. 15. berman rm, cappiello a, anand a, et al. antidepressant effects of ketamine in depressed patients. biol psychiatry. 2000;47(4):351-4. 16. mathew sj, murrough jw, collins ka, reich dl, charney ds. riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. int j neuropsychopharmacol. 2010;13(01):71-82. 17. holi mm, pelkonen m, karlsson l, et al. psychometric properties and clinical utility of the scale for suicidal ideation (ssi) in adolescents. bmc psychiatry. 2005;5(1):8. 18. diazgranados n, ibrahim l, brutsche n, et al. rapid resolution of suicidal ideation after a single infusion of an nmda antagonist in patients with treatment-resistant major depressive disorder. j clin psychiatry. 2010;71(12):1605-11. 19. price rb, nock mk, charney ds, mathew sj. effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. biol psychiatry. 2009;66(5):522-6. 20. larkin gl, beautrais al. a preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. int j neuropsychopharmacol. 2011;14(8):1127-31. 21. thangathurai d, mogos m. ketamine alleviates fear, depression, and suicidal ideation in terminally ill patients. j palliat med. 2011;14(4):389-92. 22. us department of health and human services. national strategy for suicide prevention: goals and objectives for action. 2001 contract no.: sma 3517. 23. kuehn bm. soldier suicide rates continue to rise. jama. 2009;301(11):1111-3. emergency. 2017; 5 (1): e42 ca s e re p o rt isolated oculomotor nerve palsy following minor head trauma; a case report iraj golikhatir1, hamed aminiahidashti1∗, hasan motamed motlagh1, seyed farshad heidari1 1. emergency department, imam khomeini hospital, mazandaran university of medical sciences, sari, iran. received: may 2016; accepted: june 2016; published online: 12 january 2017 abstract: isolated third nerve palsy develops in numerous intracranial pathologies such as closed head trauma, tumor, and aneurysm. this report describes a 61 years old female with an abrasion on the left forehead and ptosis of the left eye. initial computed tomography did not reveal any causative cerebral and vascular lesions or orbital and cranial fractures. high-resolution and multi-axial enhanced magnetic resonance imaging (mri) can be helpful in diagnosis and monitoring of patients with this rare phenomenon. keywords: tomography, x-ray computed; craniocerebral trauma; magnetic resonance imaging; oculomotor nerve diseases © copyright (2017) shahid beheshti university of medical sciences cite this article as: golikhatir i, aminiahidashti h, motamed motlagh h, heidari s f. isolated oculomotor nerve palsy following minor head trauma; a case report. emergency. 2017; 5 (1): e42. 1. introduction cranial nerve lesions are the result of important kinetic forces to the brain and may develop in the course of rapid acceleration/deceleration, shearing force, skull base injury, and penetrating cranial injury (1). because of long-term follow-up, repeated surgeries, and reconstructive interventions, cranial nerve injuries have a high rate of morbidity. the trauma that damages the oculomotor nerve is usually severe and associated with other neurologic deficits, basilar skull fracture, orbital injury or subarachnoid hemorrhage (2, 3). however, in rare instances, minor blunt head trauma can cause isolated oculomotor nerve palsy without any other cranial nerve injury. nevertheless, only a few reports have described the clinical feature of such patients, and mechanisms and imaging studies of nerve damage have not been discussed in depth (4, 5). here, we report a case of isolated third nerve palsy following minor head trauma. 2. case report a 61-year-old woman was transported to the emergency department of imam khomeini hospital, sari, iran following a car accident in march 2015. the patient did not experi∗corresponding author: hamed aminiahidashti; emergency department, imam khomeini hospital, razi street, sari, iran. tel: 09113450546, email: hamedaminiahidashti@yahoo.com ence a decreased level of consciousness and on arrival, she had glasgow coma scale (gcs) score of 15/15 and did not have amnesia, nausea or vomiting. the patient’s medical history was negative for diabetes, hypertension, hyperlipidemia, smoking, and drug or substance abuse. there was no history of a previous head injury, or any other neurologic or metabolic disorder. on clinical examination, her vital signs were stable. there was no raccoon eye, battle’s sign, rhinorrhea or otorrhea. she had tenderness, edema, and limitation of left wrist. she had an abrasion on the left forehead and ptosis of the left eye with lateral deviation of the eyeball and a dilated non-reactive pupil that measured 6 mm. the patient could not elevate, depress, or adduct the right eye globe, but the eye intorted on attempted down gaze. ophthalmologic tests of vision and intraocular pressure were within normal ranges in both eyes. her left eye had normal range of movement with a normal size reactive pupil. no other abnormality was noted in the neurological exam. ophthalmological consult ruled out direct trauma to the globe. brain computed tomography (ct) scan, brain magnetic resonance imaging (mri) and magnetic resonance angiogram (mra) were normal (figures 1 and 2). four-vessel angiography was normal one week after the head trauma. she was treated with oral prednisone in a tapering dose over several weeks. at the time of follow-up two months after trauma, her ptosis did not improve. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com i. golikhatir et al. 2 figure 1: brain computed tomography scan and magnetic resonance imaging of patient. 3. discussion the oculomotor nerve, stems from the frontal surface of mesencephalon, advances forward in the subarachnoid space between the superior and posterior cerebellar artery, and enters the lateral wall of the cavernous sinus by passing through the medial portion of the uncus. at the level of the superior orbital fissure, it divides into the ramus superior and ramus inferior branches. along this course, fascicules are labeled as the subarachnoid segment, cavernous segment, orbital apex segment, and intra orbital segment, located in the neighborhood of the internal carotid artery, basilar artery and its branches, and the brainstem (6-8). head trauma is responsible for 8-16% of oculomotor nerve palsies (7-9). tectal hematomas, transtentorial herniation, and isolated oculomotor palsy induced by nerve avulsion or tension at the pontine-mesencephalic junction can develop. multiple cranial nerve injuries involving the third nerve may occur in skull base fractures involving the cavernous sinus and in maxillofacial or superior orbital fissure injuries; prevalence of isolated third nerve injury due to trauma is reported to be 21% (6, 10, 11). because traumatic oculomotor nerve palsy is highly associated with skull or cervical spine fracture and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e42 figure 2: brain magnetic resonance angiogram of patient. intracranial injury, all possible causes and additional injuries should be ruled out with clinical examination and imaging investigation (12). brain ct and ct angiography are recommended in acutely traumatized patients with oculomotor nerve palsy to rapidly evaluate blood, bone, supratentorial structure, and vascular anomaly. cerebral mri is also applied because ct scans may fail to detect abnormalities in the midbrain and the oculomotor nerve itself. on admission, the absence of other neurological signs and normal brain mri suggested the lesion was most likely within the subarachnoid space, as the other important structures near the oculomotor nerve, such as the brainstem, cavernous sinus and orbit, were intact. in conclusion, the current case had minor head trauma with pure isolated third nerve palsy and a nonreactive dilated pupil, with no abnormal finding on brain ct, mri, mra and angiography. as this appears to be a rare case, additional information is necessary to clarify the mechanism in general or specific to this case. 4. appendix 4.1. acknowledgements the authors appreciate the insightful cooperation of emergency department staff of imam khomeini hospital, sari, iran. 4.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest none. 4.4. funding none. references 1. patel p, kalyanaraman s, reginald j, natarajan p, ganapathy k, suresh bapu k, et al. post-traumatic cranial nerve injury. indian j neurotrauma. 2005;2(1):27-32. 2. memon my, paine k. direct injury of the oculomotor nerve in craniocerebral trauma. journal of neurosurgery. 1971;35(4):461-4. 3. nagaseki y, shimizu t, kakizawa t, fukamachi a, nukui h. primary internal ophthalmoplegia due to head injury. acta neurochirurgica. 1989;97(3-4):117-22. 4. chen c, pai y, wang r, wang t, chong c. isolated oculomotor nerve palsy from minor head trauma. british journal of sports medicine. 2005;39(8):e34-e. 5. kaido t, tanaka y, kanemoto y, katsuragi y, okura h. traumatic oculomotor nerve palsy. journal of clinical neuroscience. 2006;13(8):852-5. 6. bhatoe hs. trauma to the cranial nerves. the indian journal of neurotrauma. 2007;4(2):89-100. 7. foroozan r. transsphenoidal diplopia. survey of ophthalmology. 2004;49(3):349-58. 8. keane jr, baloh rw. post-traumatic cranial neuropathies. the neurology of trauma: saunders philadelphia; 1992. p. 849-68. 9. rucker cw. the causes of paralysis of the third, fourth and sixth cranial nerves. american journal of ophthalthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com i. golikhatir et al. 4 mology. 1966;61(5):1293-8. 10. rush ja, younge br. paralysis of cranial nerves iii, iv, and vi: cause and prognosis in 1,000 cases. archives of ophthalmology. 1981;99(1):76-9. 11. mccormick w. pathology of closed head injury. neurosurgery. 1985;2:2639-66. 12. kuo l-t, huang ap-h, yang c-c, tsai s-y, tu y-k, huang s-j. clinical outcome of mild head injury with isolated oculomotor nerve palsy. journal of neurotrauma. 2010;27(11):1959-64. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion appendix references archives of academic emergency medicine. 2022; 10(1): e59 or i g i n a l re s e a rc h an epidemiologic overview of traumatic vascular injures in emergency department; a retrospective crosssectional study niloofar mirdamadi1,2, maryam bakhtiari1,2, alireza baratloo1,2∗, mohammad reza fattahi3, pezhman farshidmehr2,4 † 1. research center for trauma in police operations, directorate of health, rescue and treatment, police headquarter, tehran, iran. 2. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 3. sina trauma and surgery research center, tehran university of medical sciences, tehran, iran. 4. department of vascular surgery, school of medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: may 2022; accepted: june 2022; published online: 21 july 2022 abstract: introduction: vascular system injuries (vsis) are one of the main causes of preventable mortality and morbidity of trauma patients. this study aimed to evaluate baseline characteristics, presenting signs, managements, and outcomes of patients presenting to emergency department (ed) with traumatic vsis. methods: this retrospective cross-sectional study was conducted on patients with traumatic vsis admitted to the ed of a referral tertiary trauma center, during one year. using a pre-prepared checklist, demographics, pre-hospital care, type of vsis, injury severity score (iss), anatomical location of trauma, associated injuries, method of surgery, complications, and outcome were collected from patients’ profiles and reported. results: one hundred and twelve patients with the mean age of 33.5 ± 14.7 (range = 8 80) years were studied (90.2% male). most of the patients were categorized as mild or moderate in terms of their iss. 90 (80.4%) patients had at least one soft sign and 99 (88.4%) patients had at least one hard sign. isolated arterial injury was diagnosed in 90 (80.4%) patients, isolated venous injuries in 12 (10.7%) cases, and combined arteriovenous injuries in 10 (8.7%) patients. the most common associated injury was tendon rupture (63.4%) and nerve injuries were present in 60.7% of patients. 1 (0.9%) patient died, 6 (5.4%) patients went through amputation, and 3 (2.7%) patients were discharged against medical advice. the rest of the patients were discharged in perfect health. there was a significant correlation between trauma type (p = 0.001), upper and lower extremity trauma (p < 0.001), presence of distal ischemia and lack of pulse (p = 0.041), penetrating injury close to a major vessel (p = 0.006), type of injured vessels and arteries (p<0.001), injury to nerve (p = 0.011) and tendon (p = 0.007), presence of open fracture (p = 0.005), multiple trauma (p < 0.001), method of surgery (p < 0.001), and number of postoperative complications (p< 0.001) with poor outcome. conclusion: the findings showed that the majority of the studied patients were young males, most of whom were discharged in perfect situation. those who presented with higher iss, or were affected by blunt trauma or injury to lower limb arteries had worse outcome than the others. keywords: emergency service, hospital; epidemiology: patient outcome assessment; vascular system injuries; wounds and injuries cite this article as: mirdamadi n, bakhtiari m, baratloo a, fattahi mr, farshidmehr p. an epidemiologic overview of traumatic vascular injures in emergency department; a retrospective cross-sectional study. arch acad emerg med. 2022; 10(1): e59. https://doi.org/10.22037/aaem.v10i1.1663. ∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, tehran, iran. tel: +989122884364; email: arbaratloo@sina.tums.ac.ir, orcid: https://orcid.org/0000-0002-4383-7738. † corresponding author: pezhman farshidmehr; department of vascular surgery, sina hospital, tehran, iran. tel: +989133158851; email: pezhmanfarshidmehr@gmail.com, orcid: https://orcid.org/0000-0002-1492-6934. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. mirdamadi et al. 2 1. introduction vascular system injuries (vsis) cause 20% of deaths following civilian traumatic events. it was reported that about 1.5% and 1-2% of civilian trauma patients in the us and australia, respectively, suffer from a vsi; and the overall mortality resulting from vsis is 20-26% (1, 2). vsis have become one of the main causes of preventable mortality and morbidity in trauma patients (3-5). vsis are also one of the most challenging types of trauma regarding the demand of medical staff’s urgent attention and specific interventions (6-8). the management of these patients in the emergency department (ed), as well as selecting the management method are always accompanied by many challenges. it is likely that, periodically reviewing these cases can provide valuable information to the madical team, so such studies have been proposed as a necessity. therefore, this study was conducted to present the statistics and patterns of civilian traumatic vsis in a referral center. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on patients with traumatic vsis admitted to the ed of sina hospital, a referral tertiary trauma center in tehran, iran. the study proposal was approved by the ethics committee of tehran university of medical sciences (codes: ir.tums.sinahospital.rec.1399.095 and ir.tums.sinahospital.rec.1399.096). patients’ personal information were gathered, analyzed, and presented anonymously. the researchers adhered to the ethical principles of helsinki recommendations. 2.2. participants sample selection was performed using census manner, so all trauma patients with clinical evidence of vsis admitted to the hospital, from 1 november 2018 until 30 october 2019, were included. those with incomplete or distorted information in their hospital files were excluded. 2.3. data gathering data regarding demographics, pre-hospital care, radiology, presentation to operation interval, type of vsis, the injured vessels, nature of injuries, blood pressure (bp) on admission, glasgow coma scale (gcs) on admission, injury severity score (iss) , hard signs (including pulsatile bleeding, expanding hematoma, signs of distal ischemia, and absent pulse) and soft signs (including non-expanding hematoma, injury to an adjacent nerve, penetrating injury to a major vessel, and unexplained hypotension), anatomical location of trauma (neck, thorax, abdomen, upper and lower extremities), blood transfusion, associated injuries, method of surgery (end-to-end anastomosis, ligation, and saphenous vein interposition), comorbidities, complications, length of hospital stay, and outcome were collected using a predesigned checklist. data were extracted from patients’ profile. the required information was collected in advance by trained experts in the form of national trauma registry of iran. 2.4. outcome outcomes included discharge in perfect health, discharge against medical advice, amputation, or death; of which amputation and death were considered as poor outcomes. 2.5. statistical analysis all statistical analyses were conducted using the spss-25 (ibm spss statistics for windows, version 25.0. armonk, ny: ibm corp; 2017). study findings were reported as frequency (%) or mean ± standard deviation (sd) for categorical and numerical variables, respectively. the comparisons were done using chi-square or fisher’s exact test. the mean differences of numerical variables in the two group were compared using independent t-test. the p-values lower than 0.05 were considered statically significant. 3. results 3.1. baseline characteristics one hundred and twelve patients with the mean age of 33.5 ± 14.7 (range: 8 80) years were studied (90.2% male). the baseline characteristics of the studied patients are presented in table 1. most of the patients were categorized as mild or moderate in terms of their iss. penetrating trauma was present in 98 (84.8%) patients and blunt trauma in 14 (12.5%) cases. the most frequent site of injury was upper extremities (88.4%). table 2 lists the frequency of hard and soft signs of vsi on admission. 90 (80.4%) patients had at least one soft sign and 99 (88.4%) patients had at least one hard sign. pulsatile bleeding and lack of pulse were the most common hard signs. 3.2. management table 3 summarized the management, operative findings, and outcomes of patients. among the patients who underwent imaging prior to surgery, computed tomography angiography (cta) was the most frequent imaging modality. blood transfusion prior or during surgery was performed for 27 (24.1%) patients. the time interval between taking the patient to the ed and transferring them to the operating room varied from 1 to 21 hours (the median of the duration was 4 hours). open surgery was performed for all the patients. during exthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e59 table 1: baseline characteristics of the studied patients (n=112) variable number (%) sex male 101 (90.2) female 11 (9.8) age group (years) <20 20 (17.9) 20-40 69 (61.6) >40 23 (20.5) nationality iranian 105 (93.8) noniranian 7 (6.3) marital status single 73 (65.2) married 39 (34.8) glasgow coma scale 15 88 (78.6) <15 5 (4.5) not recorded 19 (16.9) prehospital care performed 84 (75.0) not performed 28 (25.0) injury severity score minor (1-8) 54 (48.2) moderate (9-15) 51 (45.5) serious (16-24) 7 (6.3) severe (25-49) 0 (0.0) critical (50-74) 0 (0.0) maximum 75 0 (0.0) type of trauma penetrating 98 (87.6) blunt 14 (13.4) anatomical location neck 12 (10.7) thorax 5 (4.5) abdomen 5 (4.5) upper extremities 99 (88.4) lower extremities 13 (11.6) ploration and surgery, isolated arterial injury was diagnosed in 90 (80.4%) patients, isolated venous injury in 12 (10.7%) cases, and combined arteriovenous injury in 10 (8.7%) patients. the most common associated injury was tendon rupture, which accounted for 63.4% of all the cases. nerve injuries were present in 60.7% of patients. 3.3. outcomes one (0.9%) patient died; 6 (5.4%) patients went through amputation, and 3 (2.7%) patients were discharged against medical advice. the rest of the patients were discharged in perfect health. 9 (8%) patients had one and 5 (4.5 %) patients had two postoperative complications. surgical site and graft infection was the most commonly reported postoperative complication. the mean length of hospital stay of the study patients was 7.66±10.73 days; and the mean hospitalization cost of them was 1241.68 ± 1600.46 us $ (136584670.14 ± table 2: frequency of hard and soft signs in the studied patients variable number (%) soft signs non-expanding hematoma 3 (2.7) injury to an adjacent nerve 58 (51.8) penetrating injury close to a major vessel 57 (50.9) unexplained hypotension 1 (0.9) hard signs pulsatile bleeding 68 (60.7) absent pulse 68(60.7) signs of distal ischemia 14 (12.5) expanding hematoma 1 (0.9) audible bruit 0 (0.0) palpable thrill 0 (0.0) 176050580.13 irr). there was a significant correlation between trauma type (p = 0.001), trauma to upper and lower extremity trauma (p < 0.001), presence of distal ischemia and lack of pulse (p = 0.041), penetrating injury close to a major vessel (p = 0.006), type of injured vessels and arteries (p<0.001), injury to nerve (p = 0.011) and tendon (p = 0.007), presence of open fracture (p = 0.005), multiple trauma (p < 0.001), method of surgery (p < 0.001), and number of postoperative complications (p< 0.001) with poor outcome. 4. discussion more than 100 patients with traumatic vsis were evaluated in this study. the majority of them were young males, and most were discharged in perfect condition; albeit there were some with poor outcomes. isolated arterial injury was the most commonly diagnosed vsi, followed by venous injuries, and combined arteriovenous injuries. tendon rupture was the most common associated injury. those who presented with higher iss, or were affected by blunt trauma or injury to lower limb arteries had worse outcomes than the others. the retrospective analysis of the patients admitted during the one-year study period showed that the majority of the patients were males between the ages of 20-40 years old. the preponderance of males in patients with vsis has been mentioned in other studies (3, 4, 6, 9-12). but when it comes to age, the average age of the patients was reported in both young and middle-aged ranges (3, 4, 6, 9-12). pre-hospital emergency cares were provided for 75% of the patients in our study. in this study, any action in order to control bleeding, such as pressure dressing, was considered a pre-hospital care, so the reported statistics are higher than that of reported in a previous similar study (13). the iss score showed great efficiency in predicting the severity of the outcome, and it was known that those with higher iss had a significantly higher risk of severe outcome (3, 12). as expected, patients with higher iss were more frequently this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. mirdamadi et al. 4 table 3: patients’ management, on operative findings, and outcomes variable number (%) imaging performed cta 13 (11.6) color doppler sonography 7 (6.3) angiography 5 (4.5) cta + color doppler sonography 2 (1.8) none 85 (75.9) type of vessel vein 12 (10.7) artery 90 (80.4) both 10 (8.9) nature of injury complete tear 97 (86.6) partial tear 9 (8.0) thrombosis 4 (3.6) pseudo aneurysm 0 (0.0) other 2 (1.8) injured artery axillary 2 (2.0) brachial 13 (13.0) radial 22 (22.0) ulnar 39 (39.0) femoral 1 (1.0) popliteal 7 (7.0) ulnar and radial 10 (10.0) other 6 (6.0) associated injuries tendon 71 (63.4) nerve 68 (60.7) open fracture 8 (7.1) closed fracture 2 (1.8) blood transfusion performed 27 (24.1) not performed 85 (75.9) method of surgery end-to-end anastomosis 55 (49.5) ligation 35 (31.5) saphenous vein graft 17 (15.2) ligation and anastomosis 1 (0.9) none 3 (2.7) unclear 1(0.9) outcome discharged after procedure 102 (91.1) amputation 6 (5.4) discharged against medical advice 3 (2.7) mortality 1 (0.9) postoperative complication surgical site and graft infection 8 (7.1) compartment syndromes 7 (6.3) failure of vascular repair or reconstruction 6 (5.4) anastomotic complication 2 (1.8) cta: computed tomography angiography faced with severe outcome. in our study, the majority of the traumas were due to penetrating injuries, mostly to upper extremities, frequently causing ulnar artery tear. upper-extremity trauma is much more common in large urban trauma centers, such as tehran, which includes a higher percentage of penetrating injuries. conversely, medical centers located in a less violent areas, such as rural areas, typically include a higher percentage of blunt injuries, most often due to motor vehicle collisions (mvc) (14). nevertheless, blunt trauma and lower extremity injuries were more likely to cause severe outcomes, compared to other locations and mechanisms. findings suggest that the anatomical location of the injury is more important than the number of anatomical sites injured in the occurrence of severe outcome. as for the mechanism of the trauma, the results are similar to reports by baram et al. (6) in kurdistan and perkins et al. (3) in united kingdom (uk), in which penetrating injuries were more common than blunt injuries (3, 6). in our study, the most common mechanism of injury, among both blunt and penetrating traumas, were mvc and stab wound, retrospectively. similar to the study by perkins et al. (3) in the uk, stab wounds were the most frequent cause of penetrating vsis, and mvc and falling from height were the predominant causes of blunt vsis (3). but in study of baram et al. (6) in kurdistan, only 15% of injuries were caused by stab wound and the majority of recorded vsis were caused by high velocity missile gunshot (6). in a study by menakuru et al. (10), conducted in north india, blunt injuries accounted for 84% of the assessed injuries (falling from height and mvc were the most common mechanisms). blunt injuries were also more frequent in a study by sah et al. (9) from nepal (68%) and meyer et al. (4) from germany (60, 4%), that in both studies, mvcs were the predominant cause of traumatic vsis. in a study conducted in the same center (sina hospital in tehran, iran) by salimi et al. (11) over a period of 14 months (between march 2002 to may 2003), blunt injury was reported in 56.1% of the cases, in which, mvc (especially while motorcycling) was the most common mechanism of injury followed by sharp objects, especially stab wounds. as for the anatomical location of the trauma, in studies by menakuru et al. (10) and baram et al. (6), brachial artery was injured most commonly followed by the superficial femoral and popliteal arteries; and meyer et al. (4) reported that the most commonly affected artery was the popliteal artery, followed by the axillar artery. in studies by menakuru et al. (10) and sah et al. (9), upper limb injury was more common than lower limb vsis. but in a previous study conducted in the same center, injuries to the lower limb were more common and the most common anatomical site of vascular injury was knee (11). a factor that may contribute to the distribution of penetrating and blunt injuries is the location of injury, and the relationship between the outcome and this variable had been this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e59 mentioned in many studies (4, 12, 14, 15); but in few previous reports, like ours, there was not any statistical significant difference in this regard (3, 14). it should be mentioned that most of the previous studies pointed that amputation rate and mortality depended on location of injury, and patients with lower extremity injury had a higher risk of severe outcome (3, 15, 16); and the rate of severe outcome was significantly higher in patients with femoral, popliteal or brachial injury compared to other sites (4, 12, 17). in our study, patients mostly presented with pulsatile bleeding, lack of pulse, and injury to an adjunct nerve, which was similar to the report by salimi et al. (11). the presence of distal ischemia and lack of pulse were independent predictors of severe outcome (16). in our study, patients with two or three hard signs faced severe outcome more frequently. any delay in diagnosing vsi can cause ischemia and irreversible damage, and in cases where clinical examination indicates vsi, delaying treatment for diagnostic procedures is not indicated (9). in this study, 76% of the patients were sent to the operating room without performing imaging. among those patients who underwent radiological procedures, cta was used for most of the cases. in a report from sah et al. (9), the majority of the cases (53%) were diagnosed using duplex, followed by additional imaging using cta in 30% of the case, while just 17% of the cases were diagnosed only on clinical judgment. in a study by meyer at al. (4) in germany, cta was used in almost 60% of the cases pre-operatively. the importance of early presentation after vsi is wellrecognized and six hours has long been considered as the golden time after peripheral vsi (18). in our study, the time interval between arrival to the ed and patients’ transfer to the operating room varied from 1 to 21 hours and the median duration was 4 hours. in comparison, in a study done by myers et al. (19) in usa, the time reported from hospital arrival to the operation room, determined in 66 patients, was 162 minutes (10 to 720 minutes). the reason for this time difference, is that in patients with stable hemodynamics, surgery was postponed so that both vascular and reconstructive surgeries were performed simultaneously, due to accompanying vascular and nerve injury. in some other published papers, presentation-operation interval was not separately reported, and mainly the time interval between the accident and the start of surgery was investigated (6, 9, 16). in this study, vsis mostly presented with associated tendon and nerve injuries, which differed from other studies where the most common associated injury was fractures (6, 9, 10). in a study done at the same center, the most common accompanying injuries were muscle injuries followed by fractures (11). in our study, patients with injury to nerve or tendon or having an open fracture as associated injury have a higher probability of severe outcome, which is in line with findings of some previous similar studies (12, 16, 17). in comparison, patients with nerve and tendon injuries had a lower percentage of severe outcome, which could be due to other associated injuries (such as fractures and multiple trauma) in people without nerve and tendon damage. open surgery was performed for all the patients in this study; and end-to-end anastomosis was the most common type of vascular reconstruction used in this study, which was similar to some similar studies (6, 9, 10). the preferred approach to vsis in upper and lower extremities, which comprised most of our patients, is open surgery. however, endovascular approaches are also used in this regard. for instance, endovascular approach was used in 11.5% of patients in a study by d’alessio et al. (12). in this study, 6 (5.4%) patients went through amputation, while amputation rates ranged from 6.4% to 14.6% in other similar studies (4, 6, 10-12). the overall postoperative mortality rate was 0.9% (1 patients), while the mortality rate in previous studies has been reported between 2.1% to 18% (3, 4, 6, 10-12). in this study, surgical site infection and compartment syndrome were the most common causes of postoperative complications. this is comparable to those reported by sah et al. (9) and menakuru et al. (10), in which this rate was reported as 6% and 11%, respectively. it is commonly believed that postoperative complications like surgical site infection and compartment syndrome are independent predictors of severe outcome (6, 12, 16, 17). this study with an average of almost one week of hospitalization had the lowest mean duration of hospitalization among similar studies (4, 11, 12), which can be explained by the large number of patients with radial and ulnar artery injury, who usually do not require long hospitalization. 5. limitations retrospective studies, in nature, are always accompanied by limitations such as missed or incomplete data. we tried to eliminate such limitations using the records of registry of “national trauma registry of iran”. about the post-operative complications, some of which may have occurred after discharge, there may be a recall bias in the process of recording patient’s information. it is noteworthy that adding early or late post–discharge outcome would be valuable. the small number of cases with amputation and other severe outcomes may also prevent the generalization of the results. 6. conclusion the findings showed that the majority of the studied patients were young males, and most were discharged in perfect health. most of the patients presented with penetrating trauma, mainly due to stab wound. the surgical manthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. mirdamadi et al. 6 agement consisted of open surgery, mostly done using endto-end anastomosis. those who presented with higher iss, or were affected by blunt trauma had worse outcomes than the others. patients with arteriovenous injuries and injury to femoral, popliteal, and brachial arteries were more likely to face severe outcomes. 7. declarations 7.1. acknowledgments we would like to express our commitment to the prehospital and hospital emergency research center affiliated to tehran university of medical sciences . 7.2. authors’ contributions the conception and design of the work by pf and ab; data acquisition by nm and mb; analysis and interpretation of data by mf, pf and ab; drafting the work by nm, mb and mf; revising it critically for important intellectual content by pf and ab; all the authors approved the final version to be published; and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are addressed. 7.3. funding and supports this study was funded with a grant from research center for trauma in police operation. 7.4. conflict of interest the authors declare that there are no conflicts of interest. references 1. perkins z, de’ath h, aylwin c, brohi k, walsh m, tai n. epidemiology and outcome of vascular trauma at a british major trauma centre. eur j vasc endovasc surg. 2012;44(2):203-9. 2. georgakarakos e, efenti gm, koutsoumpelis a, veloglou am, mechmet b, tasopoulou km, et al. five-year management of vascular injuries of the extremities in the “real-world” setting in northeastern greece: the role of iatrogenic traumas. ann vasc surg. 2021;74:264-70. 3. weller j, bowles m, summers z, bhamidipaty v. the epidemiology and outcomes of vascular trauma in gold coast, australia: institutional experience at a level 1 trauma centre. anz j surg. 2021;91(9):1893-7. 4. meyer a, huebner v, lang w, almasi-sperling v, rother u. in-hospital outcomes of patients with non-iatrogenic civilian vascular trauma. vasa. 2020;49(3):225-9. 5. salimi j, rahimpour e, zabihi mahmoudabadi h, farshidmehr p. outcomes of catheter-directed thrombolysis in patients with acute arterial thrombotic limb ischemia: a prospective interventional case series. front emerg med. 2021;5(3):e34. 6. baram a, kakamad fh, shali wf, sayed-nouri r. vascular trauma registry analysis in sulaimani province of southern kurdistan. surgical science. 2015;6(8):369-75. 7. abdolrazaghi h, haghshomar m, azadvari m. brachial plexus injury following blunt trauma; an anatomical variation in electrodiagnostic findings. front emerg med. 2021;6(2):e26. 8. abdorrazzaghi h, hajibarati b, mohammadi f. reverse sural fascio-cutaneous flap for management of patients with distal third of lower limb soft tissue defects referring to the emergency department following traumatic events; a review of 13 cases. front emerg med. 2021;5(3):e33. 9. sah b, shrestha kg, tiwari kk, reddy j. analysis of consecutive cases of vascular injury in tertiary level hospital in central nepal. j coll med sci nepal. 2017;13(3):357-62. 10. menakuru sr, behera a, jindal r, kaman l, doley r, venkatesan r. extremity vascular trauma in civilian population: a seven-year review from north india. injury. 2005;36(3):400-6. 11. salimi j, karbakhsh m, zarei m. vascular injuries in tehran: a review of 123 cases. acta med iran. 2006;44(5):333-40. 12. d’alessio i, domanin m, bissacco d, romagnoli s, rimoldi p, sammartano f, et al. operative treatment and clinical outcomes in peripheral vascular trauma: the combined experience of two centers in the endovascular era. ann vasc surg. 2020;62:342-8. 13. teixeira pg, brown cv, emigh b, long m, foreman m, eastridge b, et al. civilian prehospital tourniquet use is associated with improved survival in patients with peripheral vascular injury. j am coll surg. 2018;226(5):76976. e1. 14. franz rw, skytta ck, shah kj, hartman jf, wright ml. a five-year review of management of upper-extremity arterial injuries at an urban level i trauma center. ann vasc surg. 2012;26(5):655-64. 15. tan tw, joglar fl, hamburg nm, eberhardt rt, shaw pm, rybin d, et al. limb outcome and mortality in lower and upper extremity arterial injury: a comparison using the national trauma data bank. vasc endovascular surg. 2011;45(7):592-7. 16. topal ae, eren mn, celik y. lower extremity arterial injuries over a six-year period: outcomes, risk factors, and management. vasc health risk manag. 2010;6:1103-10. 17. rerkasem k, arworn s, thepmalai k. prognostic factors of leg amputation in patients with vascular injury: a systematic review. int j low extrem wounds. 2006;5(2):7882. 18. alarhayem aq, cohn sm, cantu-nunez o, eastridge bj, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e59 rasmussen te. impact of time to repair on outcomes in patients with lower extremity arterial injuries. j vasc surg. 2019;69(5):1519-23. 19. myers si, harward tr, maher dp, melissinos eg, lowry pa. complex upper extremity vascular trauma in an urban population. j vasc surg. 1990;12(3):305-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e5 rev i ew art i c l e canadian c-spine rule versus nexus in screening of clinically important traumatic cervical spine injuries; a systematic review and meta-analysis mohammadhossein vazirizadeh-mahabadi1, mobina yarahmadi2∗ 1. physiology research center, iran university of medical sciences, tehran, iran. 2. student research committee, school of medicine, iran university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: the canadian c-spine rule (ccr) and the national emergency x-radiography utilization study (nexus) are two criteria designed to rule-out clinically important traumatic cervical spinal cord injury (sci). in this systematic review and meta-analysis, we reviewed the articles comparing the performance of these two models. methods: search was done in medline, embase, scopus and web of science until june 2022. observational studies with direct comparison of ccr and nexus criteria in detection of clinically important cervical sci were included. two independent reviewers screened the relevant articles and summarized the data. certainty of evidence was assessed based on quadas-2. data were recorded as true positive, true negative, false positive, and false negative. then, using “diagma” package and applying weighted random effect model, area under the receiver operating characteristic (roc) curve (auc), sensitivity, specificity, negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio (dor) were calculated with 95% confidence interval (95% ci). results: we included 5 studies with direct comparison. area under the roc curve of nexus in screening of patients with clinically important cervical sci was 0.708 (95% ci: 0.647 to 0.762). pooled sensitivity and specificity of nexus criteria in screening of patients with clinically important cervical sci were 0.899 (95% ci: 0.845 to 0.936) and 0.398 (95% ci: 0.315 to 0.488). the positive and negative likelihood ratios of nexus were 1.494 (95% ci: 1.146 to 1.949) and 0.254 (95% ci: 1.155 to 1.414), respectively. diagnostic odds ratio of nexus was 5.894 (95% ci: 3.372 to 10.305). furthermore, area under the roc curve of ccr in screening of clinically important cervical sci was 0.793 (95% ci: 0.657 to 0.884). meta-analysis results showed that pooled sensitivity of ccr criteria in screening of patients with clinically important cervical sci was 0.987 (95% ci: 0.957 to 0.996) and specificity was 0.167 (95% ci: 0.073 to 0.336). the positive and negative likelihood ratios of ccr were 1.184 (95% ci: 0.837 to 1.675) and 0.081 (95% ci: 0.021 to 0.308), respectively. diagnostic odds ratio of ccr was 14.647 (95% ci: 3.678 to 58.336). conclusion: based on studies, both ccr and nexus were sensitive rules that have the potential to reduce unnecessary imaging in cervical spine trauma patients. however, the low specificity and false-positive results of both of these tools indicate that many people will continue to undergo unnecessary imaging after screening of cervical sci using these tools. in this meta-analysis, ccr appeared to have better screening accuracy. keywords: spinal cord injuries; cervical cord; wounds and injuries; diagnosis; clinical decision rules; sensitivity and specificity cite this article as: vazirizadeh-mahabadi m, yarahmadi m. canadian c-spine rule versus nexus in screening of clinically important traumatic cervical spine injuries; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e5. https://doi.org/10.22037/aaem.v11i1.1833. ∗corresponding author: mobina yarahmadi; student research committee, school of medicine, iran university of medical sciences, tehran, iran. email: moyaahmadi@gmail.com, phone: +989396332067, orcid: https://orcid.org/0000-0003-2543-8597. 1. introduction spinal cord injury (sci) is an important concern causing severe damages to patients, both in acute and chronic phases. based on the us national sci statistics report, 273,000 suffer from sci in usa (1). although, sci can occur in any part of the spinal cord, cervical sci could be the most dangerous injury, causing severe life-threatening symptoms such as this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vazirizadeh-mahabadi & m. yarahmadi 2 impaired breathing and quadriplegia (2). an important part in the primary assessment of the patients with acute spinal injury is to rule out major pathology such as fractures (3). it is important to use a proper screening method, in order to avoid acute and chronic consequences in cervical sci in trauma patients (4). imaging evaluations could help diagnose different spinal cord injuries and instabilities. however, clinically important cervical scis are found in only 3% of cervical trauma patients and other patients undergo unnecessary imaging and radiation exposure (4, 5). this low diagnostic yield, despite high imaging rates, is associated with significant costs and destructive effects on health system resources (6, 7). in addition, thyroid gland, as a radiosensitive tissue, is exposed to harmful radiation despite lack of proper diagnostic indication for imaging (8). application of rule-out criteria could help physicians diagnose clinically important cervical scis as well as reduce the unnecessary imaging evaluations (9). clinical practice guidelines recommend the use of clinical decision rules to identify patients with clinically important cervical scis. these rules help in decision-making regarding the diagnostic and treatment process based on the findings of history and physical examination and simple diagnostic tests (10, 11). the canadian c-spine rule (ccr) (12) and the national emergency x-radiography utilization study (nexus) (13) are two criteria designed to rule-out clinically important cervical scis. these tools could help in reduction of unnecessary imaging in patients with blunt trauma. ccr was first introduced in 2001 as a highly sensitive rule, applicable on alert and stable trauma patients, which could significantly reduce inefficiencies in use of c-spine radiography in emergency departments (12). nexus criteria to rule out injury to the cervical spine was introduced in 1998 and was defined as a reliable preliminary screening tool for cervical sci (13) . both of these criteria have been evaluated in multiple prospective and cohort studies over the years. currently, these criteria are recommended in guidelines as an approach to cervical spine trauma patients (14-16). despite their wide use, there is no consensus on superiority of any of the criteria over the other. therefore, in this systematic review and meta-analysis we reviewed the articles comparing the performance of ccr and nexus in detection of clinically important cervical sci. 2. methods 2.1. study design the present study was designed to compare the accuracy of ccr and nexus tools in ruling out clinically important cervical scis in blunt trauma patients. pico was as follows: p (patient/problem/population): human studies performed on cervical spine trauma patients; i (index test): nexus and ccr decision tools; c (comparison): comparison with radiologic findings; and o (outcome): clinically important cervical sci. 2.2. participants the study population included ems personnel working in urban and interurban medical emergency departments in emergency medical services (ems) affiliated to kurdistan university of medical sciences, iran. a total of 301 participants were included in the study. the inclusion criteria included willingness to participate in the study and the experience of providing care during covid-19 pandemic in medical emergencies. the exclusion criterion was not completing the questionnaires. 2.3. search strategy in the present systematic review and meta-analysis four databases, including pubmed, embase, scopus, and web of science were searched until june 2022 the search strategy was developed based on terms describing nexus and ccr. the search strategy is presented in appendix 1. we performed an extra search in grey literature and in the references of the related original articles and reviews to identify the articles missed in the database searches. 2.4. eligibility criteria randomized clinical trials (rcts), cohorts, and crosssectional studies on comparison of nexus and ccr in the same target population were included in this study. duplicated reports, retracted papers, and review studies, as well as articles assessing only one of the mentioned criteria (indirect comparison) were excluded. 2.5. data collection and risk of bias assessment the records were imported into endnote software (version x7; thomson reuters, toronto, on, canada) and duplicates were eliminated. two independent researchers selected the related articles after reviewing the title and abstract of collected records. the full texts of potentially related articles were studied in more detail. based on the eligibility criteria, related articles were selected. any disagreement was resolved using a third reviewer’s opinion. the data of the finally selected articles were extracted and imported into a checklist using excel software. the items of the checklist consisted of article features (first author name, country, year of publication, study design), characteristics of the target population (sample size, age, gender, disease history), setting of injury, type of radiographic imaging, rule-out tools’ performance (ccr or nexus), and risk of bias. quality of the included studies was assessed based on quadas-2, which is designed to assess the quality of primary diagnostic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e5 accuracy studies. 2.6. statistical analysis analysis was performed using stata 17.0 statistical software. data were recorded as true positive, true negative, false positive, and false negative. then, using “diagma” package and applying weighted random effect model, the area under the receiver operating characteristics (roc) curve (auc), sensitivity, specificity, negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio (dor) were calculated with 95% confidence interval (95% ci). i2 more than 50% was defined as high heterogeneity. deek’s funnel plot asymmetry test was used to assess publication bias. 3. results 3.1. study characteristics search in databases yielded 71 nonduplicated articles. manual search also resulted in one article. after reviewing the articles, 55 were selected, 5 of which were included in this systematic review and meta-analysis (7, 17-20). the reasons for exclusion of the selected articles were pediatric target population in the studies, lack of positive finding groups, lack of required data, non-cervical spinal trauma patients, articles evaluating only ccr or only nexus (indirect comparison), and articles being case-reports or reviews (figure 1). the included articles evaluated nexus and ccr in the same target population. all of the studies were prospective cohorts, except for one retrospective cross-sectional study. the studies included data from 14253 patients, 54.88% of whom were male. the average age range was between 34.3 to 54.6 years. all of the patients had non-penetrating cervical spine trauma. three studies had applied plain radiography to rule out critical cervical injuries and 2 had considered computed tomography scan as the gold standard tool (table 1). in total, 13689 patients were normal and 564 patients had traumatic cervical spinal injury. 3.2. diagnostic accuracy of nexus criteria auc of nexus in screening of patients with clinically important cervical scis was 0.708 (95% ci: 0.647 to 0.762) (figure 2). pooled sensitivity and specificity of nexus criteria in screening of patients with clinically important cervical scis were 0.899 (95% ci: 0.845 to 0.936) and 0.398 (95% ci: 0.315 to 0.488), respectively. the positive likelihood ratio of nexus was 1.494 (95% ci: 1.146 to 1.949) and its negative likelihood ratio was 0.254 (95% ci: 1.155 to 1.414). diagnostic odds ratio of nexus was 5.894 (95% ci: 3.372 to 10.305) (table 2). 3.3. diagnostic accuracy of ccr criteria auc of ccr in screening of patients with clinically important cervical scis was 0.793 (95% ci: 0.657 to 0.884) (figure 2). meta-analysis results showed that, pooled sensitivity of ccr criteria in screening of patients with clinically important cervical scis was 0.987 (95% ci: 0.957 to 0.996) and its specificity was 0.167 (95% ci: 0.073 to 0.336). the positive likelihood ratio of this test was 1.184 (95% ci: 0.837 to 1.675) and its negative likelihood ratio was 0.081 (95% ci: 0.021 to 0.308). diagnostic odds ratio of ccr was 14.647 (95% ci: 3.678 to 58.336) (table 2). 3.4. risk of bias assessment in the patient selection item, one study was rated as high-risk in both risk of bias and applicability domains. the other four articles had a low risk in patient selection item. in the field of index test, there were two studies with a high risk of bias, one of which was also high-risk in applicability item. all studies were low-risk in reference tests. one study had an unclear risk in flow and timing domain and one was high-risk in this field. overall, two studies had some concern and other three studies were low-risk studies (table 3). 3.5. publication bias egger’s test showed no evidence of publication bias among the studies. as shown in funnel plot (figures 2 and 3) no plot asymmetry was observed for nexus (p=0.32) and ccr (p=0.87) criteria. 4. discussion using imaging as a screening tool to rule out cervical spine injuries in blunt trauma patients is not cost-beneficial. it also exposes patients to unnecessary radiation. therefore, physicians use decision rules for screening blunt trauma patients with cervical spine injuries. the two most common decision rules used in diagnosing cervical spine injuries in blunt trauma patients are ccr and nexus (21). in the current systematic review, five studies that had evaluated the diagnostic accuracy of ccr and nexus criteria in detection of patients with clinically important cervical scis were included. it seems that ccr has a higher sensitivity, negative likelihood ratio, and diagnostic odds ratio in detection of cervical spine injuries compared to nexus. in other words, ccr is a convenient tool for determining the need for imaging and finding critical neck trauma cases. the results of our study are consistent with the previous meta-analysis in this field. similar to the findings of the present study, the previous systematic review and metaanalysis concluded that ccr has higher sensitivity than nexus(22). however, our study has an advantage, since we enrolled only the papers evaluating the effectiveness of nexus and ccr on the same population. in other words, these studies have conducted a direct comparison. the last meta-analysis in this field was conducted in 2012 by michalthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vazirizadeh-mahabadi & m. yarahmadi 4 table 1: study characteristics author, year country study design study type sample size age (year) male reference test time to reference test n csi n normal rule sensitivity specificity ala, 2018 iran prospective cohort 200 40.0 ± 17.7 139 x-ray nr 10 190 nexus 90 44.2 ccr 90 54.73 benayoun, 2016 usa retrospective cross_ sectional 760 53.6 483 ct nr 7 753 nexus 100 29.8 ccr 100 24 duane, 2013 usa prospective cohort 5182 nr nr ct 24 hr 324 4858 nexus 100 0.62 ccr 81.17 45.8 ghelichkhani, 2021 iran prospective cohort 673 34.3 ± 19.4 466 x-ray nr 61 612 nexus 100 8.3 ccr 93.4 52.3 stiell, 2003 canada prospective cohort 7438 37.6 ± 16.0 3890 x-ray nr 162 7276 nexus 99.4 45.1 ccr 90.7 36.8 csi: cervical spine injury; ct: computed tomography scan; nr: not reported; nexus: national emergency x-radiography utilization study; ccr: canadian c-spine rule. table 2: screening performance characteristics of nexus and ccr criteria in detection of patients with clinically important cervical spinal cord injuries characteristics value (95%ci) national emergency x-radiography utilization study (nexus) area under the roc curve 0.708 (0.647, 0.762) sensitivity 0.899 (0.845, 0.936) specificity 0.398 (0.315, 0.488) positive likelihood ratio 1.494 (1.146, 1.949) negative likelihood ratio 0.254 (0.155, 0.414) diagnostic odds ratio 5.894 (3.372, 10.305) canadian c-spine rule (ccr) area under the roc curve 0.793 (0.657, 0.884) sensitivity 0.987 (0.957, 0.996) specificity 0.167 (0.073, 0.336) positive likelihood ratio 1.184 (0.837, 1.675) negative likelihood ratio 0.081 (0.021, 0.308) diagnostic odds ratio 14.647 (3.678, 58.336) ci: confidence interval; roc: receiver operating characteristic. table 3: risk of bias assessment of included studies author, year risk of bias applicability overall patient selection index test reference test flow and timing patient selection index test reference test ala, 2018 low low low unclear low low low low benayoun, 2016 high high low high high low low some concern duane, 2013 low high low low low high low some concern ghelichkhani, 2021 low low low low low low low low stiell, 2003 low low low low low low low low eff et al. (22). in this paper only one study had direct comparison. it has been a decade since that article was published, and only four additional articles have been published, directly comparing ccr and nexus. there is a need for welldesigned cohort studies in this field in order to reach more reliable results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e5 figure 1: prisma flowchart of included studies. nexus: national emergency x-radiography utilization study; ccr: canadian c-spine rule. figure 2: area under the receiver operating characteristic curve (auc) of national emergency x-radiography utilization study (nexus) and canadian cervical spine rule (ccr) in detection of patients with clinically important cervical spinal cord injuries. both of these screening tools had a sensitivity of almost ninety percent. a high sensitivity in these tools was reported in the previous studies as well (23, 24). based on the age of the patients, the results may vary in studies. for instance, it has this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vazirizadeh-mahabadi & m. yarahmadi 6 figure 3: funnel plot for assessment of publication bias regarding diagnostic accuracy of national emergency x-radiography utilization study (nexus) and canadian cervical spine rule (ccr). been shown that, the sensitivity of nexus criteria decreases in older patients (23). it seems that ccr is not capable of reducing the unnecessary imaging among the geriatric cervical blunt trauma patients, because of high false positive rates. however more studies are required to prove this finding (21). therefore, despite the advantage of ccr in the screening of cervical spine injuries in blunt trauma patients, it could not yet replace nexus in geriatric age group. 5. limitation limitations of this review included the moderate methodological quality of the included studies and the heterogeneity among the studies. there are more studies evaluating the efficacy of nexus and ccr, separately. however, only five studies compared both these rules simultaneously, on the same target population. more well-designed studies are needed, in order to achieve a more reliable conclusion in this field. moreover, there was some concern regarding the risk of bias of two studies, which highlights the necessity of more well-designed studies. 6. conclusion we found that both ccr and nexus were sensitive rules that have the potential to reduce unnecessary imaging in cervical spine trauma patients. however, the low specificity and false-positive results of both of these tools indicate that many people will continue to undergo unnecessary imaging after screening of cervical sci using these tools. in this metaanalysis, the ccr rule appeared to have better screening accuracy. 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest there is no conflict of interest. 7.3. fundings and supports none. 7.4. authors’ contribution all authors have same contribution in all steps of the current study. references 1. spinal cord injury facts and figures at a glance. j spinal cord med. 2013;36(1):1-2. 2. ropper ae, neal mt, theodore n. acute management of traumatic cervical spinal cord injury. pract neurol. 2015;15(4):266-72. 3. nordin m, carragee ej, hogg-johnson s, weiner ss, hurwitz el, peloso pm, et al. assessment of neck pain and its associated disorders: results of the bone and joint decade 2000-2010 task force on neck pain and its associated disorders. spine (phila pa 1976). 2008;33(4 suppl):s101-22. 4. pimentel l, diegelmann l. evaluation and management of acute cervical spine trauma. emerg med clin north am. 2010;28(4):719-38. 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imaging of the cervical spine in trauma evaluation of ground-level fall. j trauma acute care surg. 2016;81(2):339-44. 19. duane tm, young a, mayglothling j, wilson sp, weber wf, wolfe lg, et al. ct for all or selective approach? who really needs a cervical spine ct after blunt trauma. j trauma acute care surg. 2013;74(4):1098-101. 20. ghelichkhani p, shahsavarinia k, gharekhani a, taghizadieh a, baratloo a, fattah fhr, et al. value of canadian c-spine rule versus the nexus criteria in ruling out clinically important cervical spine injuries: derivation of modified canadian c-spine rule. radiol med. 2021;126(3):414-20. 21. jeanmonod r, varacallo m. geriatric cervical spine injury. statpearls. treasure island (fl): statpearls publishing copyright © 2022, statpearls publishing llc.; 2022. 22. michaleff za, maher cg, verhagen ap, rebbeck t, lin cw. accuracy of the canadian c-spine rule and nexus to screen for clinically important cervical spine injury in patients following blunt trauma: a systematic review. cmaj. 2012;184(16):e867-76. 23. paykin g, o’reilly g, ackland h, mitra b. review article: nexus criteria to rule out cervical spine injury among older patients: a systematic review. emerg med australas. 2018;30(4):450-5. 24. mower wr, gupta m, rodriguez r, hendey gw. validation of the sensitivity of the national emergency x-radiography utilization study (nexus) head computed tomographic (ct) decision instrument for selective imaging of blunt head injury patients: an observational study. plos med. 2017;14(7):e1002313. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vazirizadeh-mahabadi & m. yarahmadi 8 appendix 1: risk of bias assessment of included studies search strategy medline (pubmed) (canadian c-spine[tiab] or low risk cervical spine criteria[tiab]) and (national emergency x-radiography utilization study[tiab] or nexus[tiab] or low risk cervical spine criteria[tiab]) embase 1‘national emergency x-radiography utilization study’:ab,ti or ‘nexus’:ab,ti or ‘low risk cervical spine criteria’:ab,ti 2’canadian c spine rule’/exp or ‘canadian c-spine’:ab,ti or ‘low risk cervical spine criteria’:ab,ti 3#1 and #2 scopus 1title-abs-key(“national emergency x-radiography utilization study” or “nexus” or “low risk cervical spine criteria”) 2title-abs-key(“canadian c-spine” or “low risk cervical spine criteria”) 3#1 and #2 web of science 1ts=(“national emergency x-radiography utilization study” or “nexus” or “low risk cervical spine criteria”) 2ts=( “canadian c-spine” or “low risk cervical spine criteria”) 3#1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references emergency. 2017; 5 (1); e59 ca s e re p o rt spontaneous adrenal hematoma in a pregnant woman; a case report mahshid ghasemi1, ali akbar beigi2, faranak behnaz3, farhad fathi2, elham memary4∗ 1. department of anesthesiology, ayatollah taleghani hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of surgery, ayatollah taleghani hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of anesthesiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. department of anesthesiology, imam hosein hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2017; accepted: february 2017; published online: 24 february 2017 abstract: spontaneous adrenal hematoma is a very rare condition and its prevalence has been reported to be about 1% in previous studies. although various causes have been proposed to explain its incidence in existing case reports, the etiology and pathology of this condition is still not known. the present study presents a case of spontaneous adrenal hematoma in a pregnant 31 year old woman without history of trauma or other probable risk factors of hemorrhage, presenting to the emergency department with chief complaint of pain in the right flank. diagnostic measures, imaging and laparotomy, confirmed the diagnosis of spontaneous adrenal hematoma for her. keywords: adrenal glands; adrenal gland diseases; hematoma; hemorrhage; rare diseases; case reports © copyright (2017) shahid beheshti university of medical sciences cite this article as: ghasemi m, beigi a, behnaz f, fathi f, memary e. spontaneous adrenal hematoma in a pregnant woman; a case report. emergency. 2017; 5 (1): e59. 1. introduction spontaneous adrenal hematoma is a very rare condition and its prevalence has been reported to be about 1% in previous studies. although various causes have been proposed to explain it in existing case reports, the etiology and pathology of this condition is still not known (1, 2). this condition is potentially life-threatening and may lead to primary adrenal insufficiency, especially in bilateral cases. delay in treatment might lead to shock, adrenal crisis and death (3, 4). this condition has only been available to researchers as case reports in existing literature. in this article, we present a rare case of unilateral spontaneous adrenal hematoma in a pregnant woman. 2. case presentation: the patient was a 31 year old gravid woman in the 13th gestational week, who presented to the emergency department ∗corresponding author: elham memary; department of anesthesiology, imam hossein hospital, shahid madani street, tehran, iran. tel: +989123870850 / e-mail: drmemary@gmail.com with complaint of right flank pain. the pain had started gradually from 3 days before and its intensity was increasing. the nature of her pain was pressing and vague and did not diffuse to other parts. it was not related to eating and changing position did not affect its intensity. the patient was not willing to eat but did not complain of nausea and vomiting. she did not have a history of miscarriage, underlying illnesses, using drugs or trauma. vital signs of the patient on arrival were blood pressure=110/70 mmhg, pulse rate=84/min, respiratory rate=18/min, and temperature=37◦c. examination of head, neck, chest and extremities did not have a pathologic finding. lung auscultation and chest opening were normal. cardiac auscultation was normal. abdomen was soft. there was a little tenderness in the right flank but no rebound and guarding. distal pulse of the extremities was full and symmetric. surgery and gynecology consultations were sought. she underwent ultrasonography and in the image, a hyper heteroechoic region in the anatomic location of adrenal gland was detected with 84×85×116 mm dimensions and 437cc volume, which was suggestive of a mass with internal hemorrhage. in addition, a little free fluid was seen around the subcapsular region of the liver and the right pleural effusion. the status of the fetus was reported to be normal. to rule out pheochromocytoma, the patient was examthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. ghasemi et al. 2 figure 1: axial abdominal magnetic resonance imaging cut of patient. ined and the results were as follows: urine vanillylmandelic acid=10.7 (normal range: 0-13.6) urine metanephrine=100 (normal range: <350) urine normetanephrine=525 (normal range: <600) during the course of hospitalization, the patient developed a severe abdominal pain and considering the drop in hemoglobin from 12 to 9.7 mg/dl, one unit of packed cells was injected for her. the patient was candidate for abdominal magnetic resonance imaging (mri), which confirmed the presence of a mass with internal hemorrhage at the location of right adrenal gland (figure 1). considering the evaluations done, the patient was finally candidate for laparotomy. a cystic mass with 12 cm diameter was found in the right adrenal and right adrenalectomia was performed and more than 1.5 l hematoma was removed. the sample was sent to pathology unit and the result of evaluating the hematoma was reported. the patient was discharged from hospital after 2 days with good general condition. 3. discussion spontaneous adrenal hematoma is a condition etiology and pathophysiology of which is still not identified. since adrenal gland is a highly vascular organ, it is prone to bleeding (1). theoretically, it seems that increase in arterial blood flow to adrenal gland and limited venous capacity of this gland, leads to blood stagnation and raises the possibility of thrombosis incidence and results in blood congestion and therefore, hemorrhage in this gland (3). yet, the considerable point is that in a significant number of reported cases, a trace of coagulation disorders can be seen. heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome, idiopathic thrombocytopenic purpura malignancy and prolonged steroid use may be introduced as risk factors of spontaneous adrenal hematoma (2, 5, 6). in addition, physiological stresses such as burn, sepsis, and post-surgery period should also be considered as potential risk factors (3). adrenal hemorrhage does not have specific manifestations and presents in various forms (7, 8). abdominal pain, vomiting, fever, drop in blood pressure and altered level of consciousness may be seen (3). although a rare occasion, in bilateral cases, clinical evidence of acute adrenal failure may arise, this may lead to cardiovascular collapse and even death (8). in very rare cases it may also manifest as an abdominal mass, in which case differentiating it from neoplastic diseases would be difficult (6). adrenal hemorrhage, especially in bilateral cases may be lifethreatening and therefore, its timely diagnosis is important. since spontaneous adrenal hemorrhage does not have specific clinical and laboratory manifestation, its clinical diagnosis is very difficult and practically impossible (7, 8). radiologic imaging is the most effective diagnostic tool and it is interesting that this condition is usually accidentally detected during abdominal computed tomography (ct) scan and is mistaken for adrenal tumor most of the time and its diagnosis is confirmed after surgery (1, 2, 9-11). color doppler ultrasonography can reveal the presence or absence of vascularization and help in differentiating spontaneous adrenal hemorrhage from malignancies such as neuroblastoma to some extent. however, it is obvious that abdominal ct scan and mri are the best diagnostic tools that also help in determining plan of surgery (10, 12). unfortunately, even these imaging measures lack sufficient specificity for diagnosis of spontaneous adrenal hemorrhage and the diagnosis is only confirmed after adrenalectomy surgery and assessing the pathology of the lesion (11). rowe et al., following a study on 18 cases of adrenal hemorrhage, reported that all of the adrenal hematomas demonstrated mass-like configuration with a well-defined, highly variable attenuation, and ovoid morphology on non-contrast ct scan. some cases had degrees of peripheral enhancement that was either thin and somewhat uniform, or heterogeneous and irregular. none of the lesions showed invasion to the peri-adrenal fat or adjacent organs (11). in case of life-threatening conditions or evidence of acute abdomen, abdominal surgery has indications. however, in other cases and when there is no confirmed diagnosis, performing surgery may be unnecessary and early steroid replacement therapy may be of priority (3, 10). in most cases of bilateral spontaneous adrenal hemorrhage, steroids should be prescribed and some even believe that this should be done even in absence of adrenal failure symptoms and especially before surgery. on the other hand, some believe that steroid replacement therapy can be delayed until manifestation of adrenal failure symptoms (4). lack of high evidence studies has made making decisions in these cases difficult and considering the small number of existing refthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1); e59 erences, it might be better to consult an endocrinologist in each case and make decisions specifically for each patient. it seems that in most cases when facing this condition, especially due to unconfirmed final diagnosis, it is decided to perform surgery. one of the other treatments for this condition is transcatheter arterial embolization (tae), which is said might prevent unnecessary surgery or at least surgery in emergency conditions that are accompanied by higher mortality rate. considering the small number of cases with this condition and rare cases of applying this interventional method, its efficiency is still a matter of question. however, in literature, case reports exist that have shown success of this method in treating spontaneous adrenal hemorrhage (9). 4. appendix 4.1. acknowledgements thanks to all the staff of surgery and anesthesiology department of ayatollah taleghani hospital, tehran, iran. 4.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declare that there is no conflict of interest. 4.4. funding none. references 1. kilinc i, dumlu eg, ozturk v, cuhaci n, balci s, yalcin a, et al. idiopathic adrenal hematoma mimiking neoplasia: a case report. international journal of surgery case reports. 2016;28:15-7. 2. alkhiari r, attar d, kraeker c. unilateral adrenal hemorrhage and the challenge of early recognition. canadian journal of general internal medicine. 2016;10(4):33-5. 3. tan gxv, sutherland t. adrenal congestion preceding adrenal hemorrhage on ct imaging: a case series. abdominal radiology. 2016;41(2):303-10. 4. song y, yu h, park k, lee j. a case of spontaneous regression of idiopathic bilateral adrenal hemorrhage in a middle aged woman: 1 year follow-up. acta endocrinologica. 2016;12(1):85-90. 5. lee s, choi d, jeong wk, song kd, min jh, kim ay, et al. frequency of hemorrhagic complications on abdominal ct in patients with warfarin therapy. clinical imaging. 2016;40(3):435-9. 6. reznichenko aa. adrenal hematoma simulating malignancy in idiopathic thrombocytopenic purpura. journal of current surgery. 2015;5(2-3):179-81. 7. sacerdote mg, johnson pt, fishman ek. ct of the adrenal gland: the many faces of adrenal hemorrhage. emergency radiology. 2012;19(1):53-60. 8. yalamanchili s. bilateral adrenal hemorrhage in a patient with antiphospholipid syndrome. the medicine forum. 2016;17(1):28-31. 9. chen l-c, lin w-r, yang s, chiu aw. successful arterial embolization for spontaneous adrenal hemorrahge: a case report. urological science. 2016;27(2):81-2. 10. martin d, suzanne m, farida a. letter to the editor: bilateral spontaneous adrenal hematoma: diagnostic difficulty of adrenal insufficiency. journal of endocrinology and diabetes mellitus. 2016;3(3):53-5. 11. rowe sp, mathur a, bishop ja, epstein ji, prescott jd, salvatori r, et al. computed tomography appearance of surgically resected adrenal hematomas. journal of computer assisted tomography. 2016;40(6):892-5. 12. trinci m, trinci cm, galluzzo m, rossi e, zeccolini m, miele v. neonatal adrenal hemorrhage. imaging nontraumatic abdominal emergencies in pediatric patients: springer; 2016. p. 181-92. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references emergency. 2016; 4 (3): 166-168 ph oto qu i z a 33-year-old man with abdominal pain kuo-chih chen1, aming chor-ming lin1,2,3, chin-chu wu4, tzong-luen wang1,3, chai-hock chua1∗ 1. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. department of intensive care unit, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. school of medicine, fu-jen catholic university, new taipei city, taiwan. 4. department of medical imaging, shin kong wu ho-su memorial hospital, taipei, taiwan. 5. division of cardiovascular surgery, department of surgery, shin kong wu ho-su memorial hospital, taipei, taiwan. received: january 2016; accepted: march 2016 cite this article as: chen k, lin a, wu ch, wang t, ch ch. a 33-year-old man with abdominal pain. emergency. 2016; 4(3):166-168. figure 1: patient’s abdominal imaging. 1. case presentation: a 33-year-old man presented to the emergency department ed) with complaint of 2-day history of abdominal pain. his pain developed with gradual onset prominently in epigastric area after eating dried mushrooms. the pain was diffuse, persistent, radiating to the back and aggravated by meal. he had been tolerating only liquids and had complaints of nausea and vomiting. he had no history of diabetes mellitus, hypertension, alcohol consumption, malignancy, or prior surgery. on arrival his blood pressure was 128/72 mmhg, with a heart rate of 101 beats/minute and a respiratory rate ∗corresponding author: chai-hock chua; division of cardiovascular surgery, department of surgery, shin kong wu ho-su memorial hospital, 95 wen chang rd, taipei 111, taiwan. tel: 886-02-28332211 ext 2082 / fax: 88602-28353547; e-mail: m002001@ms.skh.org.tw of 20 breaths/minute. he was afebrile. physical examination revealed diffuse abdominal distention, hyper-pitched bowel sounds, and tenderness more marked over the umbilicus with no guarding or rebound tenderness. a complete blood cell count showed the following: leukocyte count 12600 /mm3; segmented neutrophils 90%; hemoglobin level of 14 mg/dl; hematocrit 30%; and platelet 420000/µ l. other laboratory studies included: glucose 101 mg/dl; serum urea nitrogen 45 mg/dl; serum creatinine 2.0 mg/dl; sodium 148 meq/l; potassium 3.1 meq/l; serum glutamic oxaloacetic transaminase (sgot) 38 u/l and lipase 30 u/l. figure 1 shows patient’s plain upright abdominal x-ray as well as coronal and axial cuts of abdominal ct scan. what is your diagnosis? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 167 emergency. 2016; 4 (3): 167-168 figure 2: patient’s abdominal computed tomography scan. 2. diagnosis: abdominal ct scan showed multiple masses with peculiar shape (figure 2, arrows) in stomach and ileum. post contrast ct scan showed peculiar shape masses impacting the bowel on the middle side of the abdomen with dilated small intestine above that level. the ct scan finding was consistent with evidence of a mechanical obstruction. 3. case fate: the patient underwent conservative treatment such as nasogastric suction, decompression, aggressive intravenous fluids, bowel rest and antibiotics for 3 days. the undigested mushrooms had passed through feces later. he had an uneventful recovery with no complications. 4. discussion: intestinal obstruction is a relatively common problem encountered in the ed, accounting for an estimated 15% of all emergency admissions for abdominal pain (1-4). delayed diagnosis of small bowel obstruction is still associated significant and morbidity and mortality. early diagnosis and identification of the cause of obstruction has importance in therapeutic management (5). the diagnosis may be suspected based upon clinical history, presentation, physical examination and radiologic findings. abdominal pain and distention is the hallmark of all forms of intestinal obstruction, and constipation, nausea and vomiting are the most common symptoms. tympany to percussion and hyperpitched bowel sounds are the classic physical examination findings (6, 7). although adhesion band and incarcerated hernia are among the most common causes of small bowel obstruction, bezoars and ingested materials could be considered as less common causes (1, 8). bezoars are concretions of indigested or partially digested material in the gastrointestinal tract which divided to different types including phytobezoars, trichobezoars, pharmacobezoars and lactobezoars. an important cause of phytobezoars is dried fruits (9, 10). predisposing factors include previous gastric surgery, inadequate chewing, excessive consumption of fruits rich in fibers, renal insufficiency, hypothyroidism, and chronic constipation (11). the initial evaluation of patients with clinical signs and symptoms of intestinal obstruction should included plain upright abdominal radiography. abdominal ct scan can help to confirm the diagnosis of small bowel obstruction and identify strangulation and perforation complicating small bowel obstruction (12, 13). the bezoar could be seen on the ct scan examination. intestinal obstruction caused by bezoar not only requires immediate treatment but also recognition of underlying cause of bezoar formation (14, 15). the presence of peritoneal irritation signs usually indicates late obstruction with complications, including vascular compromise or perforation. failure to resolve with adequate bowel decompression is an indication for surgical intervention. the findings of peritonitis, clinical instability, persistent abdominal pain are concerning for intra-abdominal sepsis, intestinal ischemia, or perforation, which mandate immediate surgical exploration (16). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. chen et al. 168 5. appendix 5.1. acknowledgements we would like to express our special thanks to shin kong wu ho-su memorial hospital staff. 5.2. conflict of interest none declared. 5.3. funding and support none declared. 5.4. authors contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. jackson pg, raiji m. evaluation and management of intestinal obstruction. american family physician. 2011;83(2). 2. kariman h, shojaee m, sabzghabaei a, khatamian r, derakhshanfar h, hatamabadi h. evaluation of the alvarado score in acute abdominal pain. ulus travma acil cerrahi derg. 2014;20(2):86-90. 3. majidi a, mahmoodi s, baratloo a, mirbaha s. atypical presentation of massive pulmonary embolism, a case report. emergency. 2014;2(1):46. 4. forouzanfar m, hatamabadi h, hashemi b, majidi a, baratloo a, shahrami a, et al. outcome of nonspecific abdominal pain in the discharged patients from the emergency department. journal of gorgan university of medical sciences. 2014;16(2):62-8. 5. schwab dp, blackhurst dw, sticca rp, laws ii hl. operative acute small bowel obstruction: admitting service impacts outcome/discussion. the american surgeon. 2001;67(11):1034. 6. mullan cp, siewert b, eisenberg rl. small bowel obstruction. american journal of roentgenology. 2012;198(2):w105-w17. 7. shin c-i. small bowel obstruction. radiology illustrated: gastrointestinal tract: springer; 2015. p. 325-49. 8. markogiannakis h, messaris e, dardamanis d, pararas n, tzertzemelis d, giannopoulos p, et al. acute mechanical bowel obstruction: clinical presentation, etiology, management and outcome. world journal of gastroenterology. 2007;13(3):432. 9. gumus m, kapan m, onder a, tekbas g, yagmur y. an unusual cause of small bowel obstruction: dried apricots. jpma-journal of the pakistan medical association. 2011;61(11):1130. 10. ooi s, hong k. small bowel obstruction caused by dried apple. international journal of surgery case reports. 2015;10:154-7. 11. bedioui h, daghfous a, ayadi m, noomen r, chebbi f, rebai w, et al. a report of 15 cases of small-bowel obstruction secondary to phytobezoars: predisposing factors and diagnostic difficulties. gastroenterologie clinique et biologique. 2008;32(6):596-600. 12. thompson js. contrast radiography and intestinal obstruction. annals of surgery. 2002;236(1):7-8. 13. xu g, guo y. computed tomography findings of small bowel obstruction due to bezoar impaction: a case series. emergency medicine: open access. 2012;2012. 14. wang p-y, wang x, zhang l, li h-f, chen l, wang x, et al. bezoar-induced small bowel obstruction: clinical characteristics and diagnostic value of multi-slice spiral computed tomography. world journal of gastroenterology: wjg. 2015;21(33):9774. 15. porter dj, cosgrove c, middleton e. an unusual case of small bowel obstruction. journal of medical cases. 2015;6(11):517-9. 16. paulson ek, thompson wm. review of small-bowel obstruction: the diagnosis and when to worry. radiology. 2015;275(2):332-42. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com case presentation: diagnosis: case fate: discussion: appendix references emergency. 2016; 4 (3): 151-154 or i g i n a l re s e a rc h frequency of electrocardiographic abnormalities in tramadol poisoned patients; a brief report anahita alizadeh ghamsari1, bita dadpour1, fares najari2∗ 1. faculty member of mashhad university of medical sciences, mashhad, iran. 2. faculty member of the shahid beheshti university of medical sciences, tehran, iran. received: december 2015; accepted: january 2016 abstract: introduction: previous studies have raised the probably of cardiac manifestation in tramadol poisoning. however, conclusive information on electrocardiographic (ecg) abnormalities of tramadol overdose remains to be explained. therefore, the present study aimed to evaluate the epidemiology of ecg abnormalities in tramadol poisoned patients. methods: in a prospective cross-sectional study, all patients with tramadol poisoning, who were admitted to the emergency department of loghman hospital during 2012 2013, were evaluated. patients baseline characteristics and ecg findings including axis, rate, rhythm, pr interval, qrs duration, qtc interval, evidence of brugada pattern, and evidence of blocks were recorded. obtained data were descriptively analyzed using spss 21.0 statistical software. results: 1402 patients with the mean age of 24 ± 6 years were studied (71.1% male). sinus tachycardia was detected in 463 (33%) patients, sinus bradycardia in one patient (0.07%), right axis deviation in 340 (24.2), qrs widening in 91 (6.5%), long qtc interval in 259 (18.4%), dominant s wave in either i or avl lead in 395 (28.1%), and right bundle branch block in 73 (5.2%). increased pr interval was not detected in any cases. the evidence of brugada pattern was observed in 2 (0.14%) patients (100% male), both symptomatized with seizure. all abnormalities had same sex distribution. conclusion: based on the results of the present study, the most common types of ecg changes were sinus tachycardia, a deep s wave in leads i and avl, right axis deviation, and long qtc interval, respectively. brugada pattern and sinus bradycardia were rarely presented. keywords: tramadol; electrocardiography; arrhythmias, cardiac; drug-related side effects and adverse reactions; toxicity © copyright (2016) shahid beheshti university of medical sciences cite this article as: alizadeh ghamsari a, dadpour b, najari f. frequency of electrocardiographic abnormalities in tramadol poisoned patients; a brief report. emergency. 2016; 4(3):151-154. 1. introduction t ramadol is a synthetic centrally acting analgesic agent with opioid and non-opioid properties. due to its relatively lower risk of respiratory depression or physical dependence and better safety profile in comparison with other opiates, it is extensively used for mild to moderate pain relief (1). the main adverse reactions of tramadol are nausea, dizziness, anorexia, and most importantly seizures and hypotension, which may occur in therapeutic or toxic doses (2). the drug is available, in both parenteral and oral pharmaceutical dosage forms; and has become one of the most widely dispensed analgesics in iran’s essential drugs list since 2003. ∗corresponding author: fares najari; forensic medicine department, shohadaye tajrish hospital, shahrdari street, tajrish square, tehran, iran. email: tel: 00989123195140 , email: fares.hospital@yahoo.com. in recent years, tramadol abuse, misuse, and overdose have been dramatically increasing in iran. even international poisoning reports and suicide commitments by tramadol abuse have been increasing (3-5). triad of opiate poisoning including miosis, respiratory depression, and decreased level of consciousness can be seen in tramadol overdose too, but unlike opioids, it leads to irritability, increased deep tendon reflexes, tremor, and hypertension. other symptoms include urinary retention, rhabdomyolysis, seizures, and pulmonary edema (6, 7). as with many other drug toxicities, cardiac manifestations are also expected in tramadol poisoning. the cardiac symptoms may range from innocuous electrocardiographic (ecg) manifestations, such as sinus tachycardia, to life-threatening complications. it seems that tramadol overdose leads to some changes in the ecg through blocking of fast sodium and potassium channels (8). the study of ecg abnormality in 479 tramadol poisoned patients showed 30.6% sinus tachycardia, 24.6% qtc prolongation, and 31.7% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com fares.hospital@yahoo.com a. alizadeh ghamsari et al. 152 qrs widening (9). there is a lack of information regarding possible effects of tramadol poisoning on the cardiovascular system and the most prevalent cardiac side effects of drug. therefore, the present study was aimed to evaluate the epidemiology of ecg changes following tramadol poisoning in iranian population. 2. methods 2.1. study design and setting the present prospective cross-sectional study included tramadol poisoned patients who were admitted to emergency department (ed) of loghman hakim hospital, tehran, iran, during one year from 2012 to 2013, using census sampling. the patients with co-ingestion, history of heart disease, history of dysrhythmias, as well as chronic tramadol users were excluded. a questionnaire consisting of demographic data (age, sex), vital signs (blood pressure, heart rate, respiratory rate, level of consciousness), time to ed arrival, dose of ingestion, history of previous use, drug history, comorbid diseases, cause of ingestion, and ecg findings (axis, rate, rhythm, pr interval, qrs duration, qtc interval, evidence of brugada pattern and blocks) were filled for all participants. ecgs were performed after physical examination by an emergency specialist. the protocol of the study was confirmed by ethical committee of shahid beheshti university of medical sciences. all authors adhered to helsinki recommendations and confidentiality of patients data. all costs related to the project were incured by researchers, and no cost was imposed on patients. in addition, no changes were made in patients’ diagnosis and treatment process. 2.2. terms and definitions ecg abnormalities were defined as: sinus tachycardia (heart rate > 100 beats per minute), sinus bradycardia (heart rate < 60 beats per minute), increased pr interval (pr > 200 milliseconds), widening of the qrs duration (qrs ≥ 120 milliseconds), heart axis deviation (axis deviation in the frontal plane > 40 degree), r wave more than 1 millimeter in lead of avl, and long corrected qt interval (qtc > 440 millimeter /second). brugada pattern was defined as positive end of the qrs and st-segment elevation in right precordial leads (v1 to v3). 2.3. statistical analysis data were descriptively analyzed using spss version 21 statistical software. qualitative data were reported as frequency and percentage, and quantitative ones as mean ± standard deviation. table 1: baseline characteristics of the studied patients variables number (%) age (years) 14 25 925 (66%) 26 35 393 (28 %) 3645 84 (6%) sex male 997 (71.7%) female 405 (28.9%) heart rate /minute mean ± sd 94 ± 12.94 blood pressure (mmhg) < 90 191 (13.6%) > 90 1211 (86.4%) respiratory rate / minute < 20 1052 (75%) > 20 350 (25%) level of consciousness (gcs) 15 137 (9.8%) < 15 1265 (90.2%) time to ed arrival mean ± sd(hour) 2 ± 0.5 dose of ingestion (mg) ≥ 200 cause of ingestion intentional 400 (28.5%) un-intentional 1002 (71.5%) gcs: glasgow coma scale ; sd: standard deviation. 3. results in this prospective cross-sectional study, 1402 patients with the mean age of 24 ± 6 years (1453) were studied (71.1% male). the baseline characteristics of patients are summarized in table 1. sinus tachycardia was detected in 463 (33%) patients, sinus bradycardia in one patient (0.07%), right axis deviation in 340 (24.2), qrs widening in 91 (6.5%), long qtc interval in 259 (18.4%), dominant s wave in either i or avl lead in 395 (28.1%), and right bundle branch block in 73 (5.2%) patients. increased pr interval was not detected in any of the cases. the evidences of brugada pattern was observed in 2 (0.14%) patients (100% male), both symptomatized with seizure. table 2 shows the frequency of ecg abnormalities based on sex distribution. 4. discussion based on the results of the present study, the most common types of ecg changes were sinus tachycardia (33%), a deep s wave in leads i and avl (28%), right axis deviation (24%) and long qtc interval (18%), respectively. brugada pattern and sinus bradycardia were rarely presented. most studies concerning complications of tramadol overdose, have described central nervous system (cns) manifestations of the drug and seizure (10-14). there have been only few reports on cardiovascular toxicities including ecg abnormalities (15-17). emamhadi et al. first described ecg manifestations of trathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 153 emergency. 2016; 4 (3): 151-154 table 2: frequency of ecg abnormalities based on sex distribution abnormality number (%) sinus tachycardia (hr > 100 / minute) 463 (33%) male 438 (94.6%) female 25 (5.4%) long qrs interval widening(≥120 millisecond) 259 (18.4%) male 134 (51.7%) female 125 (48.3%) right axis deviation ( > 40 degree) 340 (24.3) male 259 (76.2%) female 81 (23.8%) dominant s wave (in i or avl leads) 394 (28%) male 372 (94.2%) female 23 (5.8%) right bundle branch block 73 (5.2%) male 40 (54.8%) female 33 (45.2%) madol overdose in a retrospective study. our results are very similar to those obtained by emamhadi’s work on 479 patients poisoned by tramadol. their findings demonstrated occurrence of tachycardia in 30.6%, long qrs duration in 7.5%, qtc > 440 millimeter/second in 24.6%, r wave height more than 1 mm in avr lead in 22.1%, right axis deviation in 31.7%, and complete or incomplete right bundle branch block in 4.6% of patients. they concluded that tramadol overdose, through fast blockade of sodium and potassium channels, leads to some changes in the ecg, which potentially may progress to life-threatening arrhythmias (9) sinus tachycardia was observed in a significant number of patients (33%) the majority of which were male (94%). although sinus tachycardia is usually non-specific for opioids, and bradycardia is a more common finding with other opioids (11, 18), our findings are in line with some other studies focusing on tramadol. in a mult-icenter prospective case series study of patients with tramadol overdose, spiller et al. observed tachycardia in 13% of patients (12). marquardt and colleagues also reported 17.4% tachycardia (19). however, in comparison with previously performed studies, the number of patients in the current study was vastly higher, although the sex ratio was not very different from other studies. this is largely because the incidence of drug poisoning in iran is not comparable to western countries. tramadol in iran is more easily and readily available compared to western countries (3). brugada pattern was seen in only 2 patients, both were male. in the study by emamhadi et al. there was one patient (among 479) with brugada pattern (9). there was also one isolated case report of brugada pattern by cole jb, which believed that sodium-channel blockade effect of tramadol was responsible for this complication of the drug (15). tramadol has been previously shown to reversibly block sodium channels especially at high concentrations. however, it is unclear that brugada syndrome existed before tramadol poisoning or is one of its complications (15, 20). qtc prolongation was also a common ecg abnormality among our patients that may also be attributed to rapid blockade of sodium channels. yet, it may also be due to a probable potassium channel blockade since tramadol has been previously shown to have inhibitory effects on potassium channels (21-23). qtc prolongation is the primary ecg manifestation of potassium channel blockers (8). qrs widening, seen in few patients, was also reported by emamhadi et al. in 7% of their patients. in this study, like other studies, no relationship between the ecg changes and amount of drug used or history of drug use was observed. finding the accurate pattern of ecg abnormality (s) of tramadol poisoning needs further multi-center studies with larger sample size. in addition, study on pharmacologic characteristics of tramadol could be helpful in discovering its mechanism of cardiac effect and ecg abnormalities that follow. 5. conclusion based on the results of the present study, the most common types of ecg changes were sinus tachycardia, a deep s wave in leads i and avl, right axis deviation, and long qtc interval, respectively. brugada pattern and sinus bradycardia were rarely presented. 6. appendix acknowledgements the authors appreciate the insightful cooperation of staff of the emergency department. author contribution all authors passed the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. conflict of interest the authors declare no conflict of interest. funding none. references 1. vazzana m, andreani t, fangueiro j, faggio c, silva c, santini a, et al. tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, coadministration of drugs and new drug delivery systems. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alizadeh ghamsari et al. 154 biomedicine, pharmacotherapy = biomedecine , pharmacotherapie. 2015;70:234-8. 2. beakley bd, kaye am, kaye ad. tramadol, pharmacology, side effects, and serotonin syndrome: a review. pain physician. 2015;18(4):395-400. 3. iravani fs, akhgari m, jokar f, bahmanabadi l. current trends in tramadol-related fatalities, tehran, iran 20052008. substance use, misuse. 2010;45(13):2162-71. 4. hassanian moghaddam h, noroozi a, zafaghandi s, bagher m, sarjami s. substance abuse warning network: pilot results in poisoned patients. razi journal of medical sciences. 2015;21(128):47-58. 5. organization wh, dependence wecod. who expert committee on drug dependence: thirty-sixth report: world health organization; 2015. 6. mehrpour o, sharifi m, zamani n. tramadol poisoning. 2015. 7. shadnia s, soltaninejad k, heydari k, sasanian g, abdollahi m. tramadol intoxication: a review of 114 cases. human , experimental toxicology. 2008;27(3):201-5. 8. lionte c, bologa c, sorodoc l. toxic and drug-induced changes of the electrocardiogram: intech open access publisher; 2012. 9. emamhadi m, sanaei-zadeh h, nikniya m, zamani n, dart rc. electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. the american journal of emergency medicine. 2012;30(8):1481-5. 10. asadi p, monsef kasmaei v, ziabari sz, zohrevandi b, moadab manesh a. prevalence of tramadol consumption in first seizure patients; a one-year cross-sectional study. emergency. 2015;3(4):159-61. 11. afshari r, afshar r, megarbane b. tramadol overdose: review of the literature. reanimation. 2011;20(5):436-41. 12. spiller ha, gorman se, villalobos d, benson be, ruskosky dr, stancavage mm, et al. prospective multicenter evaluation of tramadol exposure. journal of toxicology clinical toxicology. 1997;35(4):361-4. 13. tobias jd. seizure after overdose of tramadol. southern medical journal. 1997;90(8):826-7. 14. afshari r, ghooshkhanehee h. tramadol overdose induced seizure, dramatic rise of cpk and acute renal failure. jpma the journal of the pakistan medical association. 2009;59(3):178. 15. cole jb, sattiraju s, bilden ef, asinger rw, bertog sc. isolated tramadol overdose associated with brugada ecg pattern. pacing and clinical electrophysiology : pace. 2012;35(8):e219-21. 16. garrett pm. tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. anaesthesia and intensive care. 2004;32(4):575-7. 17. daubin c, quentin c, goulle jp, guillotin d, lehoux p, lepage o, et al. refractory shock and asystole related to tramadol overdose. clinical toxicology. 2007;45(8):961-4. 18. chen a, ashburn ma. cardiac effects of opioid therapy. pain medicine (malden, mass). 2015;16 suppl 1:s27-31. 19. marquardt ka, alsop ja, albertson te. tramadol exposures reported to statewide poison control system. the annals of pharmacotherapy. 2005;39(6):1039-44. 20. haeseler g, foadi n, ahrens j, dengler r, hecker h, leuwer m. tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. pain. 2006;126(1):234-44. 21. yalcin i, aksu f. involvement of potassium channels and nitric oxide in tramadol antinociception. pharmacology, biochemistry, and behavior. 2005;80(1):69-75. 22. cho hc, sohn jt, park ke, shin iw, chang kc, lee jw, et al. inhibitory effect of tramadol on vasorelaxation mediated by atp-sensitive k+ channels in rat aorta. canadian journal of anaesthesia = journal canadien d’anesthesie. 2007;54(6):453-60. 23. tsai ty, tsai yc, wu sn, liu yc. tramadol-induced blockade of delayed rectifier potassium current in ng108-15 neuronal cells. european journal of pain. 2006;10(7):597601. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 132 emergency (2016); 4 (3): 132-135 original research ultrasound-guided reduction of distal radius fractures anita sabzghabaei1, majid shojaee2, ali arhami dolatabadi2, mohammad manouchehrifar1, mahdi asadi2* 1. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran *corresponding author: mahdi asadi; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran; tel: +989124837764; email: drasadi2014@gmail.com received: june 2015; accepted: august 2015 abstract introduction: distal radius fractures are a common traumatic injury, particularly in the elderly population. in the present study we examined the effectiveness of ultrasound guidance in the reduction of distal radius fractures in adult patients presenting to emergency department (ed). methods: in this prospective case control study, eligible patients were adults older than 18 years who presented to the ed with distal radius fractures. 130 consecutive patient consisted of two group of sixty-five patients were prospectively enrolled for around 1 years. the first group underwent ultrasound-guided reduction and the second (control group) underwent blind reduction. all procedures were performed by two trained emergency residents under supervision of senior emergency physicians . results: baseline characteristics between two groups were similar. the rate of repeat reduction was reduced in the ultrasound group (9.2% vs 24.6%; p = .019). the post reduction radiographic indices were similar between the two groups, although the ultrasound group had improved volar tilt (mean, 7.6° vs 3.7°; p = .000). the operative rate was reduced in the ultrasound groups (10.8% vs 27.7%; p = .014). conclusion: ultrasound guidance is effective and recommended for routine use in the reduction of distal radius fractures. keywords: ultrasound; reduction, distal radius fracture; emergency department cite this article as: sabzghabaei a, shojaee m, dolatabadi aa, manouchehrifar m, asadi m. ultrasound-guided reduction of distal radius fractures. emergency. 2016; 4(3):132-135. introduction: olles’ fracture is the most common wrist fracture in adults patients (1). it is a transverse fracture of the distal radial metaphysis, which is dorsally displaced and angulated, causing the classic “dinner fork” deformity seen on physical examination. displaced distal radius fractures are usually managed with closed reduction under local or regional anesthesia, or procedural sedation and analgesia (psa). post-reduction radiographs are then obtained to assess the adequacy of the reduction. however, multiple inadequate reductions under blind manipulation can result in prolonged anesthesia time, increased sedation complication, increased radiation exposure, patient discomfort and additional investment of personnel, time and resource. using ultrasonography (us) to guide reduction could improve these shortcomings (2). ang and co-workers supported the effective role of us guidance and recommended it as a routine technique in the reduction of distal radius fractures (3). also previous studies showed that us has a good sensitivity and specificity in evaluation of long bone and wrist fracture (4-7). narihito k. et al also suggest that us assistance can aid reduction of distal radius fractures as well as fluoroscopy (8). based on diagnostic procedure, us also considered as a safe and reliable tool compared to x-ray diagnosis in juvenile fractures (9). base on the above-mentioned, the purpose of our study was to assess the accuracy of ultrasound in monitoring closed reduction of distal radius fractures. methods: study design and setting this case control study was carried out during may 2012 to december 2013 in the emergency department (ed) of haft-tir educational hospital, tehran, iran. the study protocol was approved by ethical committee of shahid beheshti university of medical sciences. we sought to compare the results of us guided colles’ fracture reductions, with the traditional technique of blind manipulation. the written informed consent was full fielded by all patients. participants the patients with diagnosis of distal radius fracture (colles) undergoing us guided reduction were enrolled c this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 133 emergency (2016); 4 (3): 132-135 around a one-year period, under a convenience sample. all patients with age <18 years, open fracture, intra-articular step off > 2 mm, neurovascular compromise, volar tilt > 0 ̊, and poor compliance were excluded. procedure in this study, fracture reduction was done under procedural sedation-analgesia by fentanyl 1 µgr/kg and propofol 0.1 mg/kg. 130 eligible patients were categorized in each group for one years. at presentation to ed, anteroposterior (ap) and lateral (lat) wrist x-rays were done to fracture confirmation. the attending emergency physician performed all reduction procedures and ulrasonographies. two trained junior emergency residents performed traction-counterattraction at the three first finger and the arm under supervision of senior emergency physician. 7.5 mhz linear array us probe (sonoscape ssi-5500bw) was used to examine the fracture site by orienting the probe along the longitudinal plane on the dorsal and radial aspects of the radius. during the reduction, us views may be repeated as necessary until aligning the proximal and distal cortices into as straight a line as possible, seen in both ap and lat views. the other group underwent reduction by the same condition but without us guidance. after reduction and immobilization, ap and lat control x-rays were obtained for two groups. the accepted criteria for successful reduction were: volar tilt > 0 ̊, radial inclination angle of 15-25 ̊, and radial height > 5 mm. another attempt was made in the cases of unsuccessful reduction. final decisions for operative or conservative management were made by the orthopedic surgeon at either inpatient or outpatient settings. 65 patient underwent us guided and 65 cases underwent blind reduction. two residents of was trained about 20 hours regarding performance of us and fracture reduction. statistical analysis spss 20 (spss, chicago, il, usa) was used to analyze the data. preand post-reduction x-ray criteria such as volar tilt, radial inclination angle, radial height; number of attempts for reduction; successful reduction rate; and need for open reduction in operating room were compared between 2 groups.the student t test was used to compare the difference in means between the groups and the χ 2 and fisher exact tests were used to compare the different rates between groups. results were considered statistically significant at the p < 0.05 level. results: 130 patients with colles’ fracture were divided to two equal groups of us guided and blind fracture manipulation. table 1 demonstrates the baseline characteristics’ of studied participants. the most common cause of injury was falling on outstretched hand (60%). as table 1 show there was no significant difference regarding sex, age, trauma mechanism, side of injury, and initial fracture indices between groups. table 2 shows the result of pre and post reduction fracture indices. the post reduction radiographic indices were similar between the two table 1: baseline characteristics of two studied groups ultrasonography (%) blind manipulation (%) p age, mean (sd): 36.5 (15.8) 38.6 (17.1) 0.46 sex male 53 (81.5) 51 (78.5) 0.51 female 12 (18.5) 14 (21.5) mechanism of trauma accident 22 (33.8) 25 (38.5) 0.80 falling 40 (61.5) 38 (58.5) direct trauma 3 (4.6) 2 (3.1) side of fracture right 32 (49.2) 33 (50.8) 0.81 left 32 (49.2) 30 (46.2) right and left 1 (1.5) 2 (3.1) fracture indices volar tilt -21.4 (13.1) -19.1 (14.3) 0 .325 radial inclination 1 6.12 (6.3) 7.0 (5.3) 0 .346 radial height 1 8.0 (2.0) 7.8 (2.2) 0 .512 table 2: post reduction x-ray fracture indices between two groups fracture indices ultrasonography (%) blind manipulation (%) p volar tilt 7.6 (5.2) 3.7 (6.0) < 0.001 radial inclination 18.8 (4.00) 18.4 (4.08) 0 .559 radial height 10.1 (2.4) 9.4 (2.7) 0 .181 http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com sabzghabaei et al 134 groups, except for volar tilt (mean, 7.6° vs 3.7°; p < 0.001). the delta volar tilt in the us group was 29◦ compared to 22.8◦ for the other group. table 3 compares the measured outcomes between two groups. the need for further attempt was significantly reduced in the ultrasound group (6 (9.2%) vs. 16 (24.6%); p = .019). the need for open reduction was significantly reduced in the us groups (7 (10.8%) vs. 18 (27.7%); p = .014). discussion: in this study, repeated attempts at reduction were significantly reduced by using us guidance. there was significantly improvement in volar tilt and decrease of operative rate. most patients with a displaced distal radius fracture are initially managed with closed reduction under fluoroscopy or without imaging assistance in the ed (8). fluoroscopy is not readily available in all eds and the patient and physician are exposed to radiation. reduction without imaging guidance result in multiple attempt, more need for post reduction radiograph, increased patient discomfort, and radiation exposure. restoring the volar angle itself result in better functional outcome and is an important indicator for surgery. obviously, ultrasound cannot directly measure radial height, radial inclination, or volar tilt, but alignment of the distal and proximal bony fragments of the radius in two planes can indirectly predict amount of these indices. us has a good sensitivity and specificity in evaluation of long bone (4, 5) and wrist fracture (6, 7). us also is a useful tool in evaluation and reduction attempt in infants (1013). multiple studies have been declared the successful utility of us in reduction of different type of fractures. ang et al. stated that us guidance is effective and recommended it for routine use in the reduction of distal radius fracture (8). shiang-hu et al. reported that us group had improved volar tilt (mean, 5.93° vs 2.61°; p = .048). they also reported that operative rate was also reduced in this group (4.9% vs 16.7%; p = .02) (3). in the current study the accepted (successful) reduction was better in ultrasound group 92% (60/65) than blind group 78% (51/65). narihito k. et al reported successful reduction of 95% (41/43) in ultrasound group versus 68%, that was in line with our findings (15/22) (8). sono-guided reduction is an accurate, simple, and safe technique that provides the considerable advantage of real-time observation. the advantages of us guidance over blind manipulation are decrease the number of reduction attempts and consequently fewer traumas to the surrounding soft tissues (3). the greatest value in us-guided reduction may lie in its ability to provide the practitioner with immediate imaging of bony alignment after each reduction maneuver, therefore decreasing the need for repeat procedural sedations and removal and reapplication of the splint (3, 7, 14). finally, while us has some limitations that prevent it from completely replacing conventional radiography, it can facilitate the reduction and prevent repeated reduction attempts. there were some limitations of our study. due to our design limitations, we did not study whether the use of us could decrease the time spent in the ed or not. also as our limitation of resource and overcrowding, we couldn’t use finger trap for traction and instead of it two person performed tractioncounterattraction at the three first finger and the arm. however, it was performed similarly in both ultrasound and control groups. conclusion: it seems that, ultrasonography is a suitable guidance tools for wrist fracture reduction and is recommended for routine use in real-time monitoring of close reductions. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. gartland jj, werley cw. evaluation of healed colles'fractures. the journal of bone & joint surgery. 1951;33(4):895-907. table 3: comparison of reduction outcome between two groups ultrasonography (%) blind manipulation (%) p reduction quality accepted 60 (92.3) 51 (78.5) 0.025 non-accepted 5 (7.7) 14 (21.5) number of reduction 1 59 (90.8) 49 (75.4) 0 .019 ≥ 2 6 (9.2) 16 (24.6) type of fixation casting 58 (89.2) 47 (72.3) 0.014 orif 7 (10.8) 18 (27.7) orif: open reduction and internal fixation. http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 135 emergency (2016); 4 (3): 132-135 2. esmailian m, zargarbashi eh, masoumi b, karami m. accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures. emergency. 2013;1(1):pp. 7-10. 3. ang s-h, lee s-w, lam k-y. ultrasound-guided reduction of distal radius fractures. the american journal of emergency medicine. 2010;28(9):1002-8. 4. weinberg er, tunik mg, tsung jw. accuracy of clinicianperformed point-of-care ultrasound for the diagnosis of fractures in children and young adults. injury. 2010;41(8):8628. 5. heiner jd, proffitt am, mcarthur tj. the ability of emergency nurses to detect simulated long bone fractures with portable ultrasound. international emergency nursing. 2011;19(3):1204. 6. fusetti c, poletti pa, pradel ph, et al. diagnosis of occult scaphoid fracture with high-spatial-resolution sonography: a prospective blind study. journal of trauma and acute care surgery. 2005;59(3):677-81. 7. hauger o, bonnefoy o, moinard m, bersani d, diard f. occult fractures of the waist of the scaphoid: early diagnosis by highspatial-resolution sonography. american journal of roentgenology. 2002;178(5):1239-45. 8. kodama n, takemura y, ueba h, imai s, matsusue y. ultrasound-assisted closed reduction of distal radius fractures. the journal of hand surgery. 2014;39(7):1287-94. 9. ackermann o, liedgens p, eckert k, et al. ultrasound diagnosis of juvenile forearm fractures. journal of medical ultrasonics. 2010;37(3):123-7. 10. cross kp. bedside ultrasound for pediatric long bone fractures. clinical pediatric emergency medicine. 2011;12(1):27-36. 11. levy ja, bachur rg. bedside ultrasound in the pediatric emergency department. current opinion in pediatrics. 2008;20(3):352-242. 12. chen l, kim y, moore cl. diagnosis and guided reduction of forearm fractures in children using bedside ultrasound. pediatric emergency care. 2007;23(8):528-31. 13. tsung jw, blaivas m. dynamic scanning in the transverse plane for ultrasound-guided fracture reduction. pediatric emergency care. 2009;25(11):805. 14. majeed m, mukherjee a, paw r. ultrasound-guided hematoma block and fracture reduction: a new way to go forward. critical care. 2010;14(suppl 1):1-2 http://www.jemerg.com/ emergency 2016; 4 (4): 188-191 or i g i n a l re s e a rc h screening characteristics of ultrasonography in detection of ankle fractures majid shojaee1, farhad hakimzadeh1∗, parisa mohammadi1, anita sabzghabaei2, mohammad manouchehrifar2, ali arhami dolatabadi1 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2015; accepted: september 2015 abstract: introduction: ankle fracture is one of the most common joint fractures. x-ray and physical examination are its main methods of diagnosis. recently, ultrasonography (us) is considered as a simple and non-invasive method of fracture diagnosis. this study evaluated the diagnostic accuracy of us in detection of ankle fracture in comparison to plain radiography. methods: in this diagnostic accuracy study, which was done in emergency departments of imam hossein and shohadaye tajrish hospitals, tehran, iran, during 2014, 141 patients with suspected diagnosis of distal leg or ankle fracture were examined by us and radiography (gold standard), independently. screening performance characteristics of us in detection of distal leg fractures were calculated using spss version 21. results: 141 patients with the mean age of 34 ± 11.52 years (range: 15–50) were evaluated (75.9% male). radiography confirmed ankle fracture in 102 (72.3%) patients. there was a significant correlation between the results of us and radiography [agreement: 95%; kappa: 0.88 (95% ci: 0.80–0.97); p < 0.001]. the screening performance characteristics of us in detection ankle fracture were as follows: sensitivity 98.9% (95% ci: 93.5% 99.9%), specificity 86.4% (95% ci: 71.9%–94.3%), ppv 94.1% (95% ci: 87.1%–97.6%), npv 97.4% (95% ci: 84.9%– 99.8%), plr 16 (95% ci: 7.3–34.8), and nlr 0.02 (95% ci: 0.003 – 0.182). the area under the roc curve of us in this regard was 95.8 (95% ci: 91.9 ± 99.7). conclusion: according to the results of this study, we can use us as an accurate and non-invasive method with high sensitivity and specificity in diagnosis of malleolus fractures. however, the inherent limitations of us such as operator dependency should be considered in this regard. keywords: ankle fractures; radiography; ultrasonography; sensitivity and specificity © copyright (2016) shahid beheshti university of medical sciences cite this article as: shojaee m, hakimzadeh f, mohammadi p, sabzghabaei a, manouchehrifar m, arhami dolatabadi a. screening characteristics of ultrasonography in detection of ankle fractures. emergency. 2016; 4(4):188-191. 1. introduction f oot and ankle fractures are known as the most common traumatic injuries (1). their incidence in men is three times more than in women, due to their physical and potential differences (2–4). motor vehicle crash and sport injuries are common causes of ankle fracture, especially tibia fractures, in young people (5). a combination of clinical and radiographic findings is used for primary diagnosis of the mentioned fractures (6). ultrasonography (us) is considered as an available, economical, safe, and portable tool in fracture diagnosis. using us can resolve problems ∗corresponding author: farhad hakimzadeh; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran; tel: +989123764779; email: hakimzadehfarhad@yahoo.com. of other diagnostic tools such as radiation exposure, patient discomfort, and time investment (7). barata et al. and ekinci et al. reported high sensitivity and specificity of us in detection of long bone fractures (8, 9). in addition, esmailian et al. declared the accuracy of us in guidance and confirmation of distal radius fractures reduction (10). bianchi and his colleagues showed the valuable role of us in diagnosis of ankle’s stress fractures compared to magnetic resonance imaging (mri) and radiography (11). emergency medicine specialists are among the first line physicians responsible for management of multiple trauma patients. the accuracy of us performed by emergency physicians regarding detection of fractures is a matter of debate. therefore, the present study aimed to evaluate the screening performance characteristics of us in detection of distal leg and ankle fractures in emergency setting. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com hakimzadehfarhad@yahoo.com 189 emergency 2016; 4 (4): 189-191 2. methods 2.1. study design the present diagnostic accuracy study was done in emergency departments of imam hossein and shohadaye tajrish hospitals, tehran, iran, during 2014. the study aimed to compare the diagnostic value of us and radiography in patients with suspected traumatic ankle or distal leg fractures. the study was approved by the ethical committee of shahid beheshti university of medical sciences. the written informed consent was granted by all participants. 2.2. participants 141 patients over 15 and under 50 years old, who were admitted to the emergency department with traumatic ankle injuries, were consecutively included. all participants were suspected to have fractures of distal fibula and tibia as well as lateral and medial malleolus. the patients with hemodynamic instability, open fractures, and clear fracture diagnosis due to major deformity were excluded. in addition, the patients who were manipulated by pre-hospital emergency medical service, or orthopedics were not enrolled in the study. no additional costs were imposed on the patients and the costs of procedures were covered by the authors themselves. 2.3. intervention the us was performed by an emergency medicine resident, trained for about 10 hours in this regard under close supervision of an expert emergency physician. after the primary and secondary surveys based on advanced trauma life support guidelines (atls), the patients were examined by bedside us followed by anterior-posterior, lateral, and mortis views ankle x-ray as the gold standard. all radiographs were reviewed and interpreted by one radiologist blinded to the clinical condition of patient. all us were performed using sonoscape ssi-5500bw machine and linear 7.5–13 mhz probe in supine position. all procedures were performed under local or regional anesthesia using 0.2% lidocaine or a combination of 0.1 m g /k g intravenous midazolam and 1.5 µg /k g intravenous fentanyl. 2.4. statistical analysis data were analyzed using spss 21 (spss, chicago, il, usa). qualitative data were given as frequency and percentage, while quantitative data were reported as mean âś standard deviation. sensitivity, specificity, negative predictive value (npv ), positive predictive value (ppv ), negative likelihood ratio (nlr), and positive likelihood ratio (plr) were calculated with 95% confidence intervals. area under the receiver operating characteristic (roc) curve of us in detection of ankle fracture was calculated. p-value ≤ 0.05 was considered table 1: baseline characteristics of the patients variable number (%) sex male 105 (75.9) female 34 (24.1) side of injury left 67 (47.5) right 74 (52.5) swelling yes 115 (81.6) no 26 (18.4) ecchymosis yes 14 (9.9) no 127 (90.1) ankle pain yes 1 (0.7) no 140 (99.3) ankle tenderness yes 136 (96.5) no 5 (3.5) type of trauma direct trauma 20 (14.2) strain/sprain 28 (19.9) multiple trauma 93 (66) mechanism of injury motorcycle-car accident 22 (15.6) pedestrian-car accident 28 (19.9) falling 33 (23.4) car-car accident 11 (27.8) statistically significant. 3. results 141 patients with the mean age of 34±11.52 years (range: 15– 50) were evaluated (75.9% male). baseline characteristics of the participants is summarized in table 1. radiography confirmed ankle fracture in 102 (72.3%) patients (53.9% internal and 46.1% external malleolus fracture). there was a significant correlation between the results of us and radiography [agreement: 95%; kappa: 0.88 (95% ci: 0.80–0.97); p < 0.001]. the screening performance characteristics of us in detection ankle fracture were as follows: sensitivity 98.9% (95% ci: 93.5%–99.9%), specificity 86.4% (95% ci: 71.9%–94.3%), ppv 94.1% (95% ci: 87.1%–97.6%), npv 97.4% (95% ci: 84.9%– 99.8%), plr 16 (95% ci: 7.3–34.8), and nlr 0.02 (95% ci: 0.003–0.182). the area under the roc curve of us in this regard was 95.8 (95% ci: 91.9 ± 99.7; figure 1). 4. discussion the results of present study showed the acceptable accuracy of us in detection of ankle fracture. the sensitivity of 98.9% introduced the high screening value of us in this regard. in addition, plr of 16 declared the ability of this test to increase this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com shojaee et al. 190 figure 1: area under the receiver operating characteristic (roc) curve of ultrasonography in detection of ankle fracture. the pre-test probability of ankle fracture, considerably. although radiography has been considered as a readily available and low-cost method for diagnosis of fractures for a long time, yet problems such as radiation exposure, quality of the image, and limitations for use in pregnant women have restricted its use. these problems double, when a fracture is present and imaging is needed for confirmation of closed reduction. in their systematic review and meta-analysis, yousefifard et al. reported the pooled sensitivity and specificity of us in detection of thoracic bone fractures to be 0.97 and 0.94, respectively (20). since the use of us in emergency departments is increasing day by day, particularly for trauma patients, this study aimed to evaluate the accuracy of us in ankle fracture diagnosis. the value of us in diagnosing fractures was first introduced in 1980 and its high sensitivity and specificity has been reported in detection of long bones and wrist fractures (12– 17). canagasabey et al. reported 90.9% sensitivity and specificity of us in fracture diagnosis (17). ekinci and his colleagues supported the high accuracy of us by studying one hundred thirty one patients, reporting 100% sensitivity and 99.1% specificity (9). trinh et al. showed 100% sensitivity and 88.9% specificity of us in detection of lateral malleolar injuries in comparison with radiography (18). atilla et.al stated the valuable screening characteristics of us in a study consisting of 246 patients with acute ankle sprain (19). in addition to all the above-mentioned characteristics, we should consider the potential value of us in continuous monitoring of the fracture reduction process. although we could not overlook the inherent limitations of us such as the high dependence of its accuracy on the operator’s skill. yet, it can be useful in cases that radiography cannot be performed due to pregnancy, unstable hemodynamics, and inability to transfer the patient to the imaging unit. in addition, in some cases, verification of reductions with us can prevent the need for repeated radiography and more radiation exposure (10, 21). 5. limitation using plain radiography as a reference test, performance of us by emergency medicine residents instead of an experienced emergency physician, not considering other ankle bone fractures such as talus fracture, and not considering the probable ankle joint dislocations, are among the most important limitations of the present study. more thorough studies in this field are suggested by considering more reliable tools such as computed tomography scan. 6. conclusion the results of present study showed the acceptable accuracy of us in detection of ankle fracture. the sensitivity of 98.9% introduced the high screening value of us in this regard. in addition, plr of 16 declared the ability of this test to increase the pre-test probability of ankle fracture, considerably. 7. appendix 7.1. acknowledgements the contribution of all trauma unit staff of imam hossein and shohadaye tajrish hospitals is appreciated. this article is extracted from the residency thesis of farhad hakimzadeh. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding none. 7.4. conflict of interest none. references 1. english e. fractures and soft tissue injuries of the feet and ankle. canadian family physician. 1985;31:585. 2. mcbirnie j. the epidemiology of tibial fractures. journal of bone & joint surgery, british volume. 1995;77(3):417– 21. 3. court-brown c, rimmer s, prakash u, mcqueen m. the epidemiology of open long bone fractures. injury. 1998;29(7):529–34. 4. court-brown cm, caesar b. epidemiology of adult fractures: a review. injury. 2006;37(8):691–7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 191 emergency 2016; 4 (4): 191-191 5. haapamaki vv, kiuru mj, koskinen sk. ankle and foot injuries: analysis of mdct findings. american journal of roentgenology. 2004;183(3):615–22. 6. marder ra. current methods for the evaluation of ankle ligament injuries. the journal of bone & joint surgery. 1994;76(7):1103–11. 7. esmailian m, zargarbashi eh, masoumi b, karami m. accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures. emergency. 2013;1(1):pp. 7–10. 8. barata i, spencer r, suppiah a, raio c, ward mf, sama a. emergency ultrasound in the detection of pediatric long-bone fractures. pediatric emergency care. 2012;28(11):1154–7. 9. ekinci s, polat o, günalp m, demirkan a, koca a. the accuracy of ultrasound evaluation in foot and ankle trauma. the american journal of emergency medicine. 2013;31(11):1551–5. 10. esmailian m, haj zargarbashi e, masoumi b, karami m. accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures. emergency. 2013;1(1):4. 11. bianchi s, luong dh. stress fractures of the ankle malleoli diagnosed by ultrasound: a report of 6 cases. skeletal radiology. 2014;43(6):813–8. 12. dacruz d, taylor r, savage b, bodiwala g. ultrasound assessment of the suspected scaphoid fracture. archives of emergency medicine. 1988;5(2):97–100. 13. weinberg er, tunik mg, tsung jw. accuracy of clinicianperformed point-of-care ultrasound for the diagnosis of fractures in children and young adults. injury. 2010;41(8):862–8. 14. heiner jd, proffitt am, mcarthur tj. the ability of emergency nurses to detect simulated long bone fractures with portable ultrasound. international emergency nursing. 2011;19(3):120–4. 15. usetti c, poletti pa, pradel ph, garavaglia g, platon a, della santa dr, et al. diagnosis of occult scaphoid fracture with high-spatial-resolution sonography: a prospective blind study. journal of trauma and acute care surgery. 2005;59(3):677–81. 16. hauger o, bonnefoy o, moinard m, bersani d, diard f. occult fractures of the waist of the scaphoid: early diagnosis by high-spatial-resolution sonography. american journal of roentgenology. 2002;178(5):1239–45. 17. canagasabey md, callaghan mj, carley s. the sonographic ottawa foot and ankle rules study (the sofar study). emergency medicine journal. 2011;28(10):838– 40. 18. trinh e, mcmillan d, gough j, brewer k. emergency department use of ultrasonography to detect lateral ankle fractures. annals of emergency medicine. 2004;44(4):s61–s2. 19. atilla od, yesilaras m, kilic ty, tur fc, reisoglu a, sever m, et al. the accuracy of bedside ultrasonography as a diagnostic tool for fractures in the ankle and foot. academic emergency medicine. 2014;21(9):1058–61. 20. yousefifard m, baikpour m, ghelichkhani p, asady h, darafarin a, amini esfahani mr, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. 2015. 2015;4. 21. sabzghabaei a, shojaee m, arhami dolatabadi a, manouchehrifar m, asadi m. ultrasound-guided reduction of distal radius fractures. emergency. 2014;4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 2 emergency (2015); 3 (1): 2 letter to editor management of dysrhythmia in emergency department arash safaie* department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran *corresponding author: arash safaie, departmnet of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. e-mail: dr.safaie@yahoo.com received: 13 november 2014; acceptance: 5 december 2014 to the editor: n volume 2, no. 3 (2014) of this journal an interesting case report, describing a patient with atrial filbrillation (af) and wolff-parkinson-white syndrome (wpw), was published (1). as the respective authors described, the patient was a 23-year-old man who had palpitation, on the electrocardiograph (ecg), which was provided, we saw irregular monomorphic wide complex tachycardia with a heart rate of about 150 per minute. the patient was treated with digoxin and consequently developed severe lethargy, weakness, sweating and bradycardia. post treatment ecg showed normal sinus rhythm (heart rate about 60) and obvious signs of wpw syndrome (short pr interval, initial delta waves and wide qrs). based on post treatment ecg and response to procainamide, the authors concluded that administering digoxin in this patient was wrong and had resulted in the patient's symptoms. i would like to share my points of view on this case with your respective readers: 1. signs suggesting concurrence of af and wpw on ecg are rapid ventricular rate (too rapid for conduction through atrioventricular (av) node; more than 180-200 in most literature) and wide bizarre polymorphic qrs complexes (resulting from either varying fusions of impulses conducted through accessory pathway and av node or existence of multiple aps) (2-5). based on his pretreatment ecg, the patient did not have any of the two mentioned criteria (he had monomorphic wide complex irregular tachycardia with a heart rate of about 150). to this date, no guideline has recommended assuming any case of af with widened qrs as wpw concurrency. as the patient did not show any signs suggesting wpw, using digoxin was not wrong based on ecg findings (despite the fact that if the physician knew about his wpw digoxin administration was surely wrong). therefore, it seems that symptoms that developed post digoxin administration were not related to the patient’s rhythm or baseline wpw syndrome. 2. based on 2014 aha/acc guideline for the management of patients with af, intravenous procainamide or ibutilide are drugs of choice in patients with af and wpw. intravenous amiodarone is contraindicated in af and wpw concurrency, just like adenosine, digoxin, or nondihydropyridine calcium channel antagonists (6). references: 1. hashemi b, pishgahi m, maleki m. worsened dysrhythmia after chemical cardioversion with digoxin; a case of malpractice. emergency. 2014;2(3):147-9. 2. fengler bt, brady wj, plautz cu. atrial fibrillation in the wolff-parkinson-white syndrome: ecg recognition and treatment in the ed. am j emerg med. 2007;25(5):576-83. 3. thanavaro jl, thanavaro s. clinical presentation and treatment of atrial fibrillation in wolff-parkinson-white syndrome. heart lung. 2010;39(2):131-6. 4. fananapazir l, german l, gallagher j, lowe j, prystowsky e. importance of preexcited qrs morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways. circulation. 1990;81(2):578-85. 5. biase ld, walsh ep. treatment of symptomatic arrhythmias associated with the wolff-parkinson-white syndrome. in: tw p, editor. uptodate. waltham, ma. 6. january ct, calkins h, murray kt, cigarroa je, stevenson wg. 2014 aha/acc/hrs guideline for the management of patients with atrial fibrillation. circulation. 2014;129:1-76. i archives of academic emergency medicine. 2023; 11(1): e36 le t t e r to ed i to r modification of standard operating procedures at the emergency department in brunei during the secondwave outbreak of covid-19; a letter to editor shehryar orakzai1, linawati jumat1, faiza alam2∗ 1. emergency department, raja isteri pengiran anak saleha hospital, ministry of health, brunei darussalam. 2. pengiran anak puteri rashidah sa’adatul bolkiah (paprsb) institute of health sciences, universiti brunei darussalam, bandar seri begawan, brunei darussalam. received: february 2023; accepted: march 2023; published online: 29 april 2023 cite this article as: orakzai s, jumat l, alam f. modification of standard operating procedures at the emergency department in brunei during the second-wave outbreak of covid-19; a letter to editor. arch acad emerg med. 2023; 11(1): e36. https://doi.org/10.22037/aaem.v11i1.1962. dear editor: following 457 days without local transmission, the second wave of covid-19 hit brunei darussalam in august 2021. this warranted the emergency department (ed) at rajaisteri-pengiran-anak-saleha hospital to revise standard operating procedures (sops). emergency department operations centre was re-activated, managing ed operations, logistics, personal protective equipment (ppe) provisions, and communication with other health facility operation centers. ed adopted the “3-d zone-separation approach”; cold/nonisolation (cz), hot/isolation (hz) and lava/quarantine zones (lz). cz patients present with symptoms other than influenza-like illness (ili), hz patients with ili, and lz patients on quarantine order/confirmed covid-19 positive. this strategy eluded the mixing of low-risk, high-risk and very-high-risk patients in the ed. patients brought/walked in were screened, categorized, and allocated by well-trained emergency medical services (ems) crew and triage nurses (figure 1). each zone had fully equipped resuscitation areas. all admitted/discharged patients from hz/lz were swabbed for sars-cov-2 pcr or given self-isolation notices, respectively, hampering community spread. ed staff in all zones wore full ppe; long-sleeve isolation gowns, shoe covers, headcovers, n95 masks, eye/face shields, and gloves. optional enhanced ppe, i.e.: jupiter suits and powered air-purifying respirators, were provided for hz and lz. there were dedicated donning/doffing areas in every ∗corresponding author: faiza alam; pengiran anak puteri rashidah sa’adatul bolkiah (paprsb) institute of health sciences, universiti brunei darussalam, bandar seri begawan, brunei darussalam. email: faiza.orakzai@gmail.com, orcid: https://orcid.org/0000-0002-4131-129x. zone. no used ppes were allowed in the clean zones (doctor’s room/offices), and regular terminal cleaning was scheduled for all zones and on an ad-hoc basis. spatial team-based rostering system (1) was adopted to reduce ed doctors’ exposure risk and unnecessary cross-staff exposure by creating i) “fixed-teams” and ii) “altered shiftlength”. five “fixed-teams” with 8-doctors; 4 covered hz/lz while 4 covered cz. each team conducted 2 hz shifts followed by 3 days off and 2 cz shifts followed by 3 days off. each shift was 12 hours (both day and night shifts, instead of 7-hour day shift and 10-hour night shift), maintaining net working hours of 48 hours/week. two short breaks were allowed during 12-hour shifts, enabling staff to doff, de-stress, and regain energy. these amendments successfully achieved the goals; (i) decreasing staff overlap time, maximizing staff physical distancing, (ii) increasing direct-care hours, reducing pressure on night-duty staff, and maintaining adequate manpower during all shifts, (iii) increasing ‘downtime’ to assist staff with mental and physical well-being. off days allowed family time and ample time to recover (if sick). during the implementation of the new sop, from august – december 2021, the doctors had zero infections; however, after the relaxation in january 2022 the numbers were on the rise. doctors don ppe before entering zones in the established “gowning area”. on exiting/entering a zone, doffing/donning was required, respectively, preventing mixing of zones (2). it worked efficaciously, limiting cross-infection and conserving cz infection-free (3). weekly assisted reproductive technology (art)s/pcrs for healthcare workers became mandatory. despite the advantages, the inevitable pitfall was unintentional exposure to a covid-positive patient in all zones, as asymptomatic patients were also treated in cz, and later dithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. orakzai et al. 2 agnosed positive. with community spread, picking out potential cases at triage became challenging. spending 12 hours in ppes was challenging, resulting in sweat-soaked scrubs and leftover facial hallmarks of n95 masks. we did not meet friends/colleagues for months. educational activities were halted, and mandatory weekly art and pcr staff surveillance was not very enjoyable. the pandemic demanded the worldwide ed network share experiences and stand united, curbing infection and paving administrative prototypes for future pandemics. 1. declarations 1.1. acknowledgments none. 1.2. conflict of interest none. 1.3. fundings and supports none. 1.4. authors’ contribution all authors have made substantial contributions to all of the following: (1) the conception and design of the study, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted and (4) agreement to be accountable for all aspects of the work. so & fa: researched literature and conceived the study. lj & so were involved in protocol development. so & fa wrote the first draft of the manuscript. all authors reviewed and edited the manuscript and approved the final version of the manuscript. references 1. brown, j. and pope, c., 2020. personal protective equipment and possible routes of airborne spread during the covid-19 pandemic. anaesthesia, 75(8), p.1116. 2. verbeek, j. h., b. rajamaki, s. ijaz, r. sauni, e. toomey, b. blackwood, c. tikka, j. h. ruotsalainen and f. s. k. balci (2020). "personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff." cochrane database syst. rev,(4). 3. chong, c.f., 2020. dividing the emergency department into red, yellow, and green zones to control covid-19 infection; a letter to editor. arch. acad. emerg. med, 8(1), pp.e60-e60. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e36 figure 1: illustration depicts the “3-d zone separation approach” at the emergency department of ripash during the covid-19 pandemic. ili: influenza-like illness; art +ve: antigen rapid test positive. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index declarations references archives of academic emergency medicine. 2022; 10(1): e85 or i g i n a l re s e a rc h association of echocardiographic findings with inhospital mortality of covid-19 patients and their changes in one-month follow-up; a cohort study seyed morsal mosallami aghili1, mehran khoshfetrat1, ali asgari2, reza arefizadeh1, aboulfazl mohsenizadeh1, seyyed hossein mousavi1∗ 1. department of cardiology, school of medicine, aja university of medical sciences, tehran, iran. 2. department of infectious diseases, school of medicine, aja university of medical sciences, tehran, iran. received: july 2022; accepted: august 2022; published online: 24 october 2022 abstract: introduction: evidence showed that cardiac complications may occur in coronavirus disease-19 (covid-19) during the acute and post-infection phases. this study aimed to evaluate the association between the echocardiographic characteristics and in-hospital mortality of covid-19 patients as well as the changes after onemonth follow-up. methods: all adult (≥18 years old) hospitalized covid-19 patients in need of echocardiography based on the guideline of the iranian society of echocardiography for performing various types of echocardiography during the covid-19 pandemic were included in this study. an expert cardiologist performed the echocardiography on all patients and also on all available patients one month after discharge. results: 146 hospitalized cases of covid-19 and 81 cases available for 1-month follow-up echocardiography were studied in this prospective study. left ventricle wall hypokinesia, aorta valve stenosis, dilated inferior vena cava (ivc), and pulmonary artery systolic pressure (pasp) of more than 35 were associated with 3.59 (95% ci: 1.19-10.79, p = 0.02), 11 (95% ci: 3.3 – 36.63, p = 0.001), 5.58 (95% ci: 1.04-29.41, p = 0.041), and 2.91 (95% ci: 1.35 – 6.3, p = 0.001) times higher odds of mortality than healthy subjects. in 1-month follow-up of patients, deterioration in lvef (p = 0.03) was detected in the not-fully vaccinated patients, and a significant decrease in pasp was observed in all cases (p = 0.04); but these changes were not clinically important. conclusion: left ventricle wall hypokinesia, aorta valve stenosis, dilated ivc, and pasp ≥ 35 were predictors of in-hospital mortality in our study. there were not any potential clinically significant differences in one-month echocardiographic follow-ups of the studied patients. keywords: covid-19; echocardiography; prognosis; mortality; sars-cov-2 cite this article as: mosallami aghili sm, khoshfetrat m, asgari a, arefizadeh r, mohsenizadeh a, mousavi sh. association of echocardiographic findings with in-hospital mortality of covid-19 patients and their changes in one-month follow-up; a cohort study. arch acad emerg med. 2022; 10(1): e85. https://doi.org/10.22037/aaem.v10i1.1787. 1. introduction since the start of the coronavirus disease-19 (covid-19) pandemic in late 2019, to august 5, 2022, the virus has spread to 228 countries and territories and caused 6 million deaths in less than 3 years (1). iran was one of the first countries to become involved in this pandemic and is one of the top 20 countries with the greatest number of covid-19 patients ∗corresponding author: seyyed hossein mousavi; aja university of medical sciences, etemadzadeh street, fatemi-gharbi street, tehran, iran. postal code: 1411718541, e-mail: dr.shmusavi@ajaums.ac.ir, tel: +982186096350, orcid: 0000-0002-0026-2989. (2, 3). although the respiratory system is the main organ involved in covid-19 infection, there is strong evidence that the virus responsible for this disease (sars-cov-2) can affect various organs, such as the heart, due to its receptor, angiotensin converting enzyme 2 (ace2) (4). the cardiac manifestations of covid-19, as important causes of its morbidity and mortality (5), vary from asymptomatic increases in cardiac biomarkers (6). the virus could injure the heart directly, due to myocarditis or infarction, or indirectly, due to shock or pulmonary complications (6). also, previous studies introduced cardiac complications such as myocardial fibrosis and arrhythmia as sequelae of longterm covid-19 (7). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. mosallami aghili et al. 2 echocardiography is a valuable tool for assessment of the cardiovascular system during covid-19 infection, because it is generally available, affordable, and can provide useful clinical information that could even impact the treatment strategies of the patients (8). most previous echocardiographic studies assessed the cardiac characteristics of infected patients during hospitalization. they demonstrated a range of cardiac complications, including left ventricular (lv ) and right ventricular (rv ) dysfunctions during the acute phase of covid-19 (6, 8-11). these characteristics have been demonstrated to be potential independent predictors of prognosis (7, 9). also, few studies evaluated post-infection cardiac complications and their related changes in echocardiography (12-14). evidence shows individuals with covid-19 are more likely to develop cardiovascular diseases of various types after the first 30 days following infection (15). due to the need to assess baseline echocardiographic characteristics of the patients as a significant factor in prognosis and the lack of follow-up studies in iran, we conducted this study to evaluate the association between the echocardiographic characteristics and in-hospital mortality of covid-19 patients as well as the changes after one-month follow-up. 2. methods 2.1. study design and setting this prospective cohort study was conducted from january 2022 to july 2022 at imam reza educational hospital, tehran, iran. the data of each covid-19 patient was checked from hospitalization to discharge or in-hospital mortality. also, one month after discharge from the hospital, patients were referred to the hospital’s cardiology clinic for follow-up echocardiography. all diagnostic and treatment processes were based on the latest version of the national covid-19 protocol. before the start of data gathering, the ethical committee of aja university of medical sciences approved the study protocol (ir.ajaums.rec.1400.261). the researchers acquired written informed consent and followed the recommendations in helsinki declaration. 2.2. study population all adults (≥18 years old) hospitalized due to covid-19 in the covid-19 ward or intensive care unit (icu) were included in this study if they had an indication for echocardiography according to “the guideline of the iranian society of echocardiography for performing various types of echocardiography during the covid-19 pandemic” (16). the indications include being in shock state or presentation of new arrythmia (except for premature atrial contraction (pac) or isolated premature ventricular contraction (pvc)), cardiomegaly in the chest ct-scan, moderate or severe pericardial effusion in the chest computed tomography (ct) scan, rise of cardiac biomarker, new or significant echocardiography (ecg) changes, generalized edema, persistent chest pain or dyspnea unexplained with pulmonary involvement, and exacerbation of the previous heart disease. covid-19 infection was confirmed using reverse transcription–polymerase chain reaction (rt-pcr) in all cases. pregnancy, out-of-hospital mortality, and personal request for withdrawal from the project were the exclusion criteria. after the request of cardiology consultation from the in-charge physician of the ward or icu, if the inclusion criteria were fulfilled, echocardiography would be performed. the inclusion criteria were checked for all of the patients by an expert cardiologist. follow-up echocardiography was performed on all of the available patients one month after discharge at the hospital cardiology clinic. 2.3. outcomes the primary outcome was in-hospital mortality. study data was described in two groups of deceased and survived patients based on the in-hospital incidences. secondary outcome was one-month follow-up changes in the echocardiographic findings, considering the vaccination as a moderator factor. 2.4. data gathering a checklist was developed for the purpose of gathering patients’ data. demographic characteristics (age and gender), medical history (diabetes mellitus, hypertension, ischemic heart disease, neurological disease, and cancer), and the history of covid-19 vaccination (0-dose, 1-dose, and 2-dose) and time of vaccination were recorded on the checklist from hospital medical records initially. patients with a history of no vaccination, 1-dose vaccination, or 2-dose vaccination in less than 2 weeks from the hospital administration against covid-19 with any of the confirmed vaccines (by the ministry of health of the islamic republic of iran) were considered as the not-fully vaccinated group, and patients with a history of 2-dose vaccination within two weeks or more before the hospital administration were considered the fully vaccinated group. neither the patients nor the assessor were blinded to vaccination states. all of the echocardiograms were performed by an expert cardiologist with more than 10 years of clinical experience in the intensive care unit (icu). follow-up echocardiography was performed by the same expert cardiologist. to reduce the measurement bias, an expert cardiologist who had a fellowship in echocardiography designed the study and chose the variables with the lowest dependence on the operator. echocardiography was performed using the vivid 3 set device (general electric company). all abnormalities discovered during an echocardiogram were evaluated and reported. the american society of echocardiography’s guidelines for interthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e85 table 1: comparing the baseline characteristics of the hospitalized covid-19 patients between survived and non-survived cases variable in-hospital mortality p no (n = 98) yes (n = 48) age (year) mean ± sd 60.94 ± 16.68 70.52 ± 14.10 0.002 gender male 54 (66.67) 27 (33.33) 0.89 female 44 (67.69) 21 (32.31) underlying disease dm 25 (59.52) 17 (40.48) 0.21 htn 41 (65.08) 22 (34.92) 0.64 ihd 20 (58.82) 14 (41.18) 0.24 nd 6 (46.15) 7 (53.85) 0.09 cancer 9 (60.00) 6 (40.00) 0.53 length of hospitalization mean ± sd 9.98 ±9.07 8.08 ±6.84 0.11 vaccination no 24 (48.00) 26 (52.00) 1 dose 24 (58.53) 17 (41.46) <0.001 2 doses 50 (90.90) 5 (9.09) data are presented as mean ± standard deviation (sd) or frequency (%). dm: diabetes mellitus; htn: hypertension; ihd: ischemic heart disease; nd: neurologic disorders. preting echocardiography were followed (17). all of the categorical echocardiographic variables including cardiac valves (mitral, aortic, tricuspid, pulmonary) abnormalities (stenosis or regurgitation), high pulmonary artery systolic pressure (pasp) (≥35mmhg), left ventricle hypertrophy (lvh), inferior vena cava (ivc) dilation, left ventricle wall motion (normal, hypokinesia, akinesia), pericardial effusion (normal, mild, moderate, severe), enlargement of ventricles (bilateral, right, left, none), left ventricular systolic dysfunction (lvsd), left ventricular diastolic dysfunction (lvdd), and right ventricular systolic dysfunction (rvsd), and also quantitative variables including left ventricle ejection fraction (%), left ventricular (lv ) end-diastolic diameter (centimeter), lv end-systolic diameter (centimeter), and pasp were extracted from the echocardiographic reports. length of stay (days), in-hospital mortality, and icu admission were extracted from hospital medical records after discharge of the patients. in-hospital mortality, and icu admission were considered as prognostic factors and the main outcomes in this study. 2.5. statistical analysis spss version 25 was used for all statistical analyses. based on the findings of kolmogorov-smirnov test for normality, none of the variables showed a normal distribution, so we used non-parametric tests for the analysis. two quantitative groups were compared using mann-whitney u test. the association of two categorical variables was assessed using the chi-square test and, when necessary, the fisher’s exact test. logistic regression was performed to calculate odds ratio (or) of echocardiographic parameters for in-hospital mortality. the wilcoxon signed-rank test was used to compare echocardiogram parameters at the baseline and 1-month follow-up. statistics were considered significant for p-values under 0.05. 3. results 3.1. baseline characteristics of patients 146 confirmed cases of covid-19 with the mean age of 64.09 ± 16.46 (range: 21-92) years were studied (55.5% male). the most frequent underlying diseases were hypertension (43.2%), diabetes mellitus (28.8%), ischemic heart disease (23.3%), cancer (10.3%), and neurological disorders (8.9%). the mean duration of hospitalization was 9.36 ± 8.4 days. 90 (61.6%) cases were admitted to the icu, and also, 48 (32.9%) cases died during hospitalization. 37.7% of cases were fully vaccinated against covid-19, 28.1% had received their first dose of vaccine, and 34.2% had not been vaccinated by the time of admission to the hospital. baseline characteristics of the patients are described in table 1 and compared between survived and non-survived cases. 3.2. echocardiographic findings and in-hospital mortality the characteristics of the in-hospital echocardiograms of the studied covid-19 patients are compared between survived and non-survived cases in table 2. there was a significant correlation between aortic valve stenosis/regurgitation (p < 0.001), hypokinesia in the left ventricle wall motion (p = this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. mosallami aghili et al. 4 table 2: echocardiographic characteristics of the patients based on their mortality status variable in-hospital mortality or (95% ci) p no (n = 98) yes (n = 48) left ventricle wall motion normal 91 (70.54) 38 (29.46) ref hypokinesia 6 (40.00) 9 (60.00) 3.59(1.19-10.79) 0.02 akinesia 0 (0.00) 1 (100.00) ne mitral valve normal 20 (74.07) 7 (25.93) constant 0.43 mild regurgitation 71 (66.98) 35 (33.02) 1.05 (0.09-11.82) 0.567 moderate regurgitation 4 (44.44) 5 (55.56) 1.48 (0.15-14.74) 0.271 stenosis 3 (75) 1 (25) 3.75 (0.27-51.37) 0.269 tricuspid valve normal 32 (69.57) 14 (30.43) constant 0.08 mild tr 60 (69.77) 26 (30.23) 0.27 (0.08-0.99) 0.126 moderate/severe tr 5 (38.46) 8 (61.54) 0.27 (0.08-0.91) 0.475 aorta valve normal 88 (77.19) 26 (22.81) ref stenosis 4 (23.53) 13 (76.47) 11 (3.3 – 36.63) 0.001 regurgitation 6 (40) 9 (60) 2.17 (0.47-9.95) 0.32 pulmonary artery systolic pressure 35 80 (73.39) 29 (26.61) ref ≥35 18 (48.65) 19 (51.35) 2.91 (1.35-6.3) 0.001 pericardial effusion no 81 (68.64) 37 (31.36) 1.37 (0.57-3.3) 0.66 mild 16 (61.54) 10 (38.46) ne severe 1 (100) 0 (0) ne left ventricle hypertrophy no 74 (64.91) 40 (35.09) 0.54 (0.21-1.36) 0.2 yes 24 (77.42) 7 (22.58) ne inferior vena cava normal 96 (69.06) 43 (30.94) ref dilated 20 (38.46) 32 (61.54) 5.58 (1.04-29.41) 0.041 enlargement of ventricles no 90 (66.67) 45 (33.33) constant 0.86 bilateral 2 (66.67) 1 (33.33) 1 (0.09-11.32) 1 lv 3 (60) 2 (40) 1.33 (0.22-8.27) 0.76 rv 3 (100) 0 (0) ne left ventricle ejection fraction, mean, sd 53.36 ± 5.75 47.28 ± 12.5 <0.001 end-diastolic diameter, mean, sd 5.11 ± 0.7 5.41 ± 0.75 0.02* end-systolic diameter, mean, sd 3.09 ± 0.55 3.74 ± 1.31 <0.001 left ventricular dysfunction normal 79 (73.15) 29 (26.85) ref mild systolic 3 (75) 1 (25) 0.91 (0.09-9.08) 0.94 significant systolic 6 (33.33) 12 (66.67) 5.45 (1.87-15.86) 0.75 mild diastolic 10 (66.67) 5 (33.33) 1.36 (0.43-4.32) 0.6 moderate diastolic 0 (0) 1 (100) ne right ventricular systolic dysfunction normal 96 (68.57) 44 (31.43) 2.59 (0.06-117.32) 0.07 mild 0 (0) 2 (100) ne moderate 0 (0) 1 (100) ne data are presented as mean ± standard deviation (sd) or frequency (%). ne: not estimated; ref: reference; or: odds ratio; ci: confidence interval; tr: tricuspid regurgitation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e85 table 3: comparing the echocardiographic parameters of covid-19 patients at the time of admission and 1-month follow-up (f/u) between vaccinated and non-vaccinated cases variable total p full vaccination p incomplete vaccination p left ventricle ejection fraction baseline 53.27 ± 6.08 0.02 54 ± 5.09 0.28 52.56 ± 6.9 0.03 f/u 52.41 ± 5.65 53.50 ± 4.11 51.34 ± 6.71 left ventricle end-diastolic diameter baseline 5.14 ± 0.71 0.79 5.17 ± 0.85 0.03 5.11 ± 0.57 0.11 f/u 5.14 ± 0.66 5.12 ± 0.78 5.16 ± 0.53 left ventricle end-systolic diameter baseline 3.14 ± 0.53 0.17 3.09 ± 0.50 0.68 3.19 ± 0.55 0.11 f/u 3.16 ± 0.48 3.11 ± 0.44 3.21 ± 0.52 pulmonary artery systolic pressure baseline 28.93 ± 7.11 0.04 28.28 ± 5.91 0.23 29.56 ± 8.13 0.93 f/u 27.93 ± 4.11 27.62 ± 4.02 28.22 ± 4.22 data are presented as mean ± standard deviation (sd). 0.017), higher levels of pasp (≥35) (p = 0.008), dilated ivc (p = 0.039), lv ejection fraction (p = 0.00), lv end systolic diameter (p = 0.001), lv end-diastolic diameter (p = 0.018), and left ventricular dysfunction (p = 0.007) with in-hospital mortality. logistic regression analysis showed that participants with hypokinesia of the left ventricle wall had 3.59 times (95% ci: 1.19–10.79, p = 0.02) higher odds of mortality than participants with normal left ventricle wall motion. also, having an aortic valve stenosis was associated with 11 times (95% ci: 3.3–36.63, p = 0.001) higher odds of mortality than subjects with a healthy aortic valve. a dilated ivc was associated with 5.58 times (95% ci: 1.04-29.41, p = 0.041) higher odds of mortality than subjects with normal ivc. subjects with pasp ≥35 had 2.91 times (95% ci: 1.35-6.3, p = 0.001) higher odds of mortality than subjects with pasp<35. data of pulmonary valve evaluation was not included in regression due to low incidence of abnormalities (1 deceased patient with stenosis and 3 patients with regurgitation, out of which 2 died). 3.3. follow-up echocardiography after one month, 81 of the 98 survived cases were available for a follow-up echocardiographic evaluation. we compared some echocardiography parameters in three groups of patients: all cases, fully vaccinated, and not-fully vaccinated (table 3). lvef decreased significantly after one month in all cases (p = 0.02). this decrease was not significant among patients who had a history of full vaccinations against covid19. furthermore, we detected a significant decrease in lv end-diastolic diameter in the vaccinated group (p = 0.03) and decrease in pasp in all cases (p = 0.004) after one month. although these changes were statistically significant, none of these differences are clinically important. 4. discussion based on the findings of the present study, echocardiography could be considered as a useful tool for detection of high-risk covid-19 patients. our analysis showed that left ventricle wall hypokinesia, aorta valve stenosis, dilated ivc, and pasp ≥ 35 were associated with 3.59 (95% ci: 1.19-10.79, p = 0.02), 11 (95% ci: 3.3 – 36.63, p = 0.001), 5.58 times (95% ci: 1.0429.41, p = 0.041), and 2.91 (95% ci: 1.35 – 6.3, p=0.001) times higher odds of in-hospital mortality. in this study, we could find abnormalities in lv parameters in patients hospitalized due to covid-19, which is in line with previous studies (8, 11). direct injuries such as myocarditis due to binding of sars-cov-2 to ace2 receptors or indirect injury due to shock and systematic involvement could lead to these complications (6, 18-21). also, we could establish a significant correlation between these abnormalities and prognosis, supporting previous evidence (9, 22). cardiac parameters also changed in the post-infection period, especially the decrease of lvef in patients who were not fully vaccinated. other follow-up studies reported lv dysfunction, similar to our study (12, 14, 23). the underlying mechanisms of the post-acute phase abnormalities are not well understood. however, a long-lasting inflammatory response brought on by persisting viral reservoirs in the heart after the acute infection (24) or an immunological reaction to cardiac antigens through molecular mimicry (25) are two potential mechanisms of delayed injury. pasp was introduced as an independent prognostic factor in the study by pishgahi et al. (9). in this study, we found that a higher level of pasp (≥35) had a significant association with in-hospital mortality (2.91 times higher odds). in our followup, pasp decreased significantly in comparison to the baseline, supporting the findings of previous studies (13, 14). this outcome may be due to the drop in pulmonary artery presthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. mosallami aghili et al. 6 sure caused by the end of the acute phase of covid-19 and its effects on the pulmonary system (23). researchers are currently working hard to identify covid-19 prediction parameters that are more reliable (26). evidence shows that cardiovascular complications are important predictors of mortality in covid-19 patients (27-29). a study in iran demonstrated that ef under 30%, rv dysfunction, collapse of the ivc, and higher levels of pasp are independent factors of death in patients with covid-19 (9). we had similar results in our logistic regression analysis. left ventricle wall hypokinesia, aortic valve stenosis, dilated ivc, and pasp ≥ 35 were predictors of in-hospital mortality in our study. our study, in-line with previous studies (10, 22, 30), reported valvular dysfunction, mostly mild regurgitation of mitral and tricuspid valves. importantly, patients with aortic valve stenosis had 11 times higher odds of mortality than patients with a normal aortic valve. the correlation between these dysfunctions and covid-19 is still vague, but they are likely related to a previously diagnosed or undiscovered disease or ventricular dilatation (8). they are not the/considered an exact indication for echocardiography, but we suppose they should be. they could be diagnosed with an exact auscultation of the heart and then referred to echocardiography. like in previous studies (11, 22, 30, 31), mild pericardial effusion (pe) was a common finding in our study, but we could not establish a significant correlation between pe and the prognosis of patients. it has been established that vaccination can prevent severe covid-19 cases, hospitalization, and mortality (32). yet more research is needed to fully understand its capacity to prevent secondary complications like cardiac complications. in the follow-up phase, we could only find a significant decrease in lvef in non-fully vaccinated patients. non-fully vaccinated patients might experience a different compensatory pattern of cardiac recovery than vaccinated patients; further long-term follow-ups are needed to investigate this matter. in-line with our study, a recent study in south korea revealed that full vaccination against covid-19 is correlated with a lower risk of acute myocardial infarction following covid-19 infection (33). 5. limitation there are some limitations in our study that should be mentioned. in this study, we only included patients hospitalized due to covid-19. therefore, our inclusion criteria would limit the generalizability of the results to patients with moderate or severe diseases that need hospitalization. echocardiography is an operator-dependent tool and a potential source of bias. however, to reduce the measurement bias, an expert cardiologist who had a fellowship in echocardiography designed the study and chose the variables with the lowest dependence on the operator. also, all of the echocardiograms were performed with the same device model and by the same person. echocardiograms were performed on different days of hospitalization, and changes in echocardiograms on different days are unclear. we performed follow-up echocardiograms only one month after discharge. further studies to evaluate serial changes in echocardiograms after covid-19 infection are recommended. 6. conclusion left ventricle wall hypokinesia, aorta valve stenosis, dilated ivc, and pasp ≥ 35 were predictors of in-hospital mortality in our study. while we did not see any potential clinically significant differences in one-month echocardiographic followups of our patients, non-fully vaccinated patients might experience a different compensatory pattern of cardiac recovery than vaccinated patients; yet, further long-term followups are needed. 7. declarations 7.1. acknowledgments we appreciate all the medical staff at the department of cardiology, the department of infectious disease, covid-19 ward, and icu, including doctors, nurses, health care experts, and staff. we also acknowledge the patients and their families for their cooperation. 7.2. author contribution study design and data gathering: all of authors. analysis: smma interpreting the results: all of authors drafting: smma, shm critically revised: shm, mk, aa, ra, am all authors read and approved the final version of the paper to be submitted. 7.3. conflict of interest the authors declare no conflict of interest. 7.4. data availability the datasets created and analyzed during the current study are accessible upon reasonable request from the corresponding author. 7.5. funding none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e85 references 1. worldometers. covid-19 coronavirus pandemic 2022 [available from: https://www.worldometers.info/coronavirus/. 2. habibi z, mosallami aghili sm, javadi sah, seifi a, karimi yarandi k, dehghan manshadi sa, et al. clinical guideline of neurosurgical practice during the covid-19 pandemic. tehran univ med j. 2021;79(2):85-92. 3. zare dehnavi a, salehi m, arab ahmadi m, asgardoon mh, ashrafi f, ahmadinejad n, et al. clinical, laboratory and imaging characteristics of hospitalized covid-19 patients with neurologic involvement; a cross-sectional study. arch acad emerg med. 2022;10(1):e10. 4. wang t, du z, zhu f, cao z, an y, gao y, et al. 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and acute myocardial infarction and ischemic stroke after covid-19 infection. jama. 2022;328(9):887-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2017; 5 (1): e52 ed u c at i o n a l sampling methods in clinical research; an educational review mohamed elfil1, ahmed negida2∗ 1. faculty of medicine, alexandria university, egypt. 2. faculty of medicine, zagazig university, egypt. received: october 2016; accepted: november 2016; published online: 14 january 2017 abstract: clinical research usually involves patients with a certain disease or a condition. the generalizability of clinical research findings is based on multiple factors related to the internal and external validity of the research methods. the main methodological issue that influences the generalizability of clinical research findings is the sampling method. in this educational article, we are explaining the different sampling methods in clinical research. keywords: research design; sampling studies; evidence-based medicine; population surveillance; education © copyright (2017) shahid beheshti university of medical sciences cite this article as: elfil m, negida a. sampling methods in clinical research; an educational review. emergency. 2017; 5 (1): e52. 1. introduction in clinical research, we define the population as a group of people who share a common character or a condition, usually the disease. if we are conducting a study on patients with ischemic stroke, it will be difficult to include the whole population of ischemic stroke all over the world. it is difficult to locate the whole population everywhere and to have access to all the population. therefore, the practical approach in clinical research is to include a part of this population, called “sample population”. the whole population is sometimes called “target population” while the sample population is called “study population. when doing a research study, we should consider the sample to be representative to the target population, as much as possible, with the least possible error and without substitution or incompleteness. the process of selecting a sample population from the target population is called the “sampling method”. 2. sampling types there are two major categories of sampling methods (figure 1): 1; probability sampling methods where all subjects ∗corresponding author: ahmed negida; faculty of medicine, zagazig university, zagazig, el-sharkia, egypt. postal code: 44519; e-mails: ahmed01251@medicine.zu.edu.eg and dr.negida@gmail.com tel: 00201125549087 in the target population have equal chances to be selected in the sample [1,2] and 2; non-probability sampling methods where the sample population is selected in a non-systematic process that does not guarantee equal chances for each subject in the target population [2,3]. samples which were selected using probability sampling methods are more representatives of the target population. 3. probability sampling method 3.1. simple random sampling this method is used when the whole population is accessible and the investigators have a list of all subjects in this target population. the list of all subjects in this population is called the “sampling frame”. from this list, we draw a random sample using lottery method or using a computer generated random list [4]. 3.2. stratified random sampling this method is a modification of the simple random sampling therefore, it requires the condition of sampling frame being available, as well. however, in this method, the whole population is divided into homogeneous strata or subgroups according a demographic factor (e.g. gender, age, religion, socio-economic level, education, or diagnosis etc.). then, the researchers select draw a random sample from the different strata [3,4]. the advantages of this method are: (1) it allows researchers to obtain an effect size from each strata this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. elfil and a. negida. 2 figure 1: sampling methods. separately, as if it was a different study. therefore, the between group differences become apparent, and (2) it allows obtaining samples from minority/under-represented populations. if the researchers used the simple random sampling, the minority population will remain underrepresented in the sample, as well. simply, because the simple random method usually represents the whole target population. in such case, investigators can better use the stratified random sample to obtain adequate samples from all strata in the population. 3.3. systematic random sampling (interval sampling) in this method, the investigators select subjects to be included in the sample based on a systematic rule, using a fixed interval. for example: if the rule is to include the last patient from every 5 patients. we will include patients with these numbers (5, 10, 15, 20, 25, ...etc.). in some situations, it is not necessary to have the sampling frame if there is a specific hospital or center which the patients are visiting regularly. in this case, the researcher can start randomly and then systemically chooses next patients using a fixed interval [4]. 3.4. cluster sampling (multistage sampling) it is used when creating a sampling frame is nearly impossible due to the large size of the population. in this method, the population is divided by geographic location into clusters. a list of all clusters is made and investigators draw a random number of clusters to be included. then, they list all individuals within these clusters, and run another turn of random selection to get a final random sample exactly as simple random sampling. this method is called multistage because the selection passed with two stages: firstly, the selection of eligible clusters, then, the selection of sample from individuals of these clusters. an example for this, if we are conducting a research project on primary school students from iran. it will be very difficult to get a list of all primary school students all over the country. in this case, a list of primary schools is made and the researcher randomly picks up a number of schools, then pick a random sample from the eligible schools [3]. 4. non-probability sampling method 4.1. convenience sampling although it is a non-probability sampling method, it is the most applicable and widely used method in clinical research. in this method, the investigators enroll subjects according to their availability and accessibility. therefore, this method is quick, inexpensive, and convenient. it is called convenient sampling as the researcher selects the sample elements according to their convenient accessibility and proximity [3,6]. for example: assume that we will perform a cohort study on egyptian patients with hepatitis c (hcv ) virus. the convenience sample here will be confined to the accessible population for the research team. accessible population are hcv patients attending in zagazig university hospital and cairo university hospitals. therefore, within the study period, all patients attending these two hospitals and meet the eligibility criteria will be included in this study. 4.2. judgmental sampling in this method, the subjects are selected by the choice of the investigators. the researcher assumes specific characteristics for the sample (e.g. male/female ratio = 2/1) and therefore, they judge the sample to be suitable for representing the population. this method is widely criticized due to the likelihood of bias by investigator judgement [5]. 4.3. snow-ball sampling this method is used when the population cannot be located in a specific place and therefore, it is different to access this population. in this method, the investigator asks each subject to give him access to his colleagues from the same population. this situation is common in social science research, for example, if we running a survey on street children, there will be no list with the homeless children and it will be difficult to locate this population in one place e.g. a school/hospital. here, the investigators will deliver the survey to one child then, ask him to take them to his colleagues or deliver the surveys to them. 5. conflict of interest none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e52 references 1. j. wretman, reflections on probability vs nonprobability sampling, offcial stat. honour daniel thorburn. (2010) 29–35. 2. a. shorten, c. moorley, selecting the sample., evid. based. nurs. 17 (2014) eb–2014–101747–. doi:10.1136/eb-2014101747. 3. f. gravetter, l. forzano, selecting research participants, res. methods behav. sci. (2012) 125–139. 4. p. sampling, p. guidelines, m.s. choices, t. oaks, chapter 5 c hoosing the t ype of, (2012) 125–174. 5. c. teddlie, f. yu, mixed methods sampling: a typology with examples, j. mix. methods res. 1 (2007) 77–100. doi:10.1177/2345678906292430. 6. t. critically, a. everyday, chapter 7 . sampling techniques introduction to sampling distinguishing between a sample and a population simple random sampling stratified random sampling convenience sampling quota sampling sample size sampling error evaluating information from samples , (n.d.) 1–23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction sampling types probability sampling method non-probability sampling method conflict of interest references emergency. 2017; 5 (1): e44 ca s e re p o rt a rare case of gastrointestinal tract foreign body; glassy stomach mohsen ebrahimi1, jafar malmir1, azadeh mahmoudi-gharaee1, mahdi foroughian2∗ 1. department of emergency medicine, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, afzalipour hospital, kerman university of medical sciences, kerman, iran. received: may 2016; accepted: july 2016; published online: 14 january 2017 abstract: ingestion of foreign bodies is common and conservative treatment can eliminated most particlesfrom the gastrointestinal tractunless peritoneal signs appear. a 22-year-old man presented to emergency department who had ingested glass particles of a crushed beverage bottle. he complained of epigastric and periumbilical pain. physical examination did not revealany peritoneal signs. abdominal x-ray showed stomach full of small glass particles. conservative treatment, without any surgical intervention,resulted insafely eliminating glass particlesin this patient. keywords: foreign bodies;glass;gastrointestinal tract; emergencies; case management © copyright (2017) shahid beheshti university of medical sciences cite this article as: ebrahimi m, malmir j, mahmoudi-gharaee a, foroughian m. a rare case of gastrointestinal tract foreign body; glassy stomach. emergency. 2017; 5 (1): e44. 1. introduction foreign bodies may be ingested, inserted into a body cavity, or deposited into the body by a traumatic or iatrogenic injury. most ingested foreign bodies pass through the gastrointestinal tract without any problem (1). however, ingested or inserted foreign bodies may cause bowel obstruction or perforation and lead to serious complications such as severe hemorrhage, abscess formation, or septicemia. most cases of foreign body ingestions are seen amongchildren and those with psychiatric disorders (2-4). here we report a case of intentional foreign body ingestion and itsoutcome. 2. case presentation a 22-year-old male was brought to emergency department with chief complaint of periumbilical and epigastric pain since 4 hours before. he explained that he had ingested crushed glasses of a beverage bottleafter a family argument. about 30 minutes after swallowing glass particles, the patient had developed irritation and pain in epigastric and periumbilical area without any other associated symptom.hedenied ∗corresponding author: mahdi foroughian ;department of emergency medicine, kerman university of medical sciences, kerman, iran. tel: 03432235011; email: mf2600@yahoo.com, history of other diseases including psychiatric problems.on physical examination normal vital signs were detected, no oral lesion or laceration or bleeding was seen. he had normal breathing sounds. abdomen had normal bowel sounds with mild epigastric tenderness without rebound tenderness or guarding. chest x-ray and abdominal x-ray were performed. chest x-ray was normal with no air under diaphragm or pneumomediastinum. abdominal x ray (figure 1) showed a stomach full of small glass particles. the patient was monitored continuously and carefully; surgical consultation was done, laparotomy was planned but patient did not agree to undergo surgical intervention. thereafter, he was monitored closely and observed in emergency department with serial physical exam. serial abdominal radiography was done every other day to evaluate the removal of the particles (figure 2). all glass particles were eliminated from the gastrointestinal tract of patient without any intervention. no complication was seen during the observation period. eventually after 10 days the patient was discharged and went home. 3. discussion: cases of intentional glass ingestionare rare, so there is no special guideline to approach them. in these cases, it is expected to see oral cavity laceration, drooling, inability to swallow, neck pain or chest pain. if the objects could pass the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. ebrahimi et al. 2 figure 1: upright abdominal x-ray showing a stomachfull of glass particles. figure 2: upright abdominal x ray, 48 hours after glass ingestion (the glass particles are in the large intestine). esophagus, mild abdominal pain or even signs of acute abdomen may appear. based on the routine approach, in order to identify the location, number and size of the ingested particles, and also evaluate the presence of any kind of complications, radiography could be suggested as an initial screening method(5). although glass foreign bodies are opaque on radiographs, but it was indicated that the size of the glass foreign body is often the limiting factor for radiographic detection and that 0.5to 2.0-mm fragments represent a “limited detection” size range(1, 6).endoscopic extraction is well accepted and recommended as a form of treatment for swallowed foreign body in upper gastrointestinal tract, however, conservative approach with proper management is also effective and preferable when foreign bodies have passed the esophagus within days without any difficulty (7). this is the treatment of choice for blunt, short (<6 cm), and narrow (<2.5 cm diameter) foreign bodies, especially once they have passed the pylorus(8). emergency esophagogastroduodenoscopy is suggested in cases of sharp or pointed foreign bodies. they can result in complications such as gastrointestinal bleeding, abscess formation, mediastinitis or peritonitis due to perforation of the gastrointestinal tract (9, 10). surgical intervention is required in such cases, which make up less than 1% of ingested foreign body cases (11). 4. appendix 4.1. acknowledgements the authors appreciate the cooperation of emergency department staff of imam reza hospital, mashhad, iran. 4.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declarethat there is noconflict of interest regarding the publication of this manuscript. 4.4. funding none. references 1. hunter tb, taljanovic ms. foreign bodies. radiographics : a review publication of the radiological society of north america, inc. 2003;23(3):731-57. 2. woolley sl, smith dr. history of possible foreign body ingestion in children: don’t forget the rarities. european journal of emergency medicine. 2005;12(6):312-6. 3. safari s, karimi e, baratloo a, alavi-moghaddam m, kalantarimeibodi m. a 16-year-old girl with acute onset respiratory distress. emergency. 2014;2(1):50. 4. haghighi m, shoaei sd. pharyngeal aspiration of complete upper denture in 90-year-old man; a case report. emergency. 2015;3(3):117. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e44 5. mosca s, manes g, martino r, amitrano l, bottino v, bove a, et al. endoscopic management of foreign bodies in the upper gastrointestinal tract: report on a series of 414 adult patients. endoscopy. 2001;33(08):692-6. 6. courter bj. radiographic screening for glass foreign bodies–what does a “negative” foreign body series really mean? annals of emergency medicine. 1990;19(9):9971000. 7. ng k. retention of an ingested small blunt foreign body. journal of the belgian society of radiology. 2011;94(6). 8. al shehri gy, al malki ta, al shehri my, ajao og, jastaniah sa, haroon ks, et al. swallowed foreign body: is interventional management always required? saudi journal of gastroenterology. 2000;6(2):84. 9. allotey j, duncan h, williams h. mediastinitis and retropharyngeal abscess following delayed diagnosis of glass ingestion. emergency medicine journal. 2006;23(2):e12-e. 10. gattai r, migliaccio ml, bonizzoli m, peris a, bechi p. upper gi hemorrhage from glass fragments’ ingestion in a patient with jejunal diverticula–case report. international journal of surgery case reports. 2015;6:191-3. 11. ambe p, weber sa, schauer m, knoefel wt. swallowed foreign bodies in adults. dtsch arztebl int. 2012;109(50):869-75. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation discussion: appendix references emergency. 2017; 5 (1): e62 or i g i n a l re s e a rc h relationship between dyspnea descriptors and underlying causes of the symptom; a cross-sectional study seyyed mohammad ali sajadi1, alireza majidi2, fahimeh abdollahimajd3∗, fatemeh jalali1 1. department of internal medicine, ali-ebne-abitaleb hospital, rafsanjan university of medical sciences, rafsanjan, iran. 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. skin research center, shahid beheshti university of medical sciences, tehran, iran. received: august 2016; accepted: march 2017; published online: 19 march 2017 abstract: introduction: history taking and physical examination help clinicians identify the patient’s problem and effectively treat it. this study aimed to evaluate the descriptors of dyspnea in patients presenting to emergency department (ed) with asthma, congestive heart failure (chf), and chronic obstructive pulmonary disease (copd). methods: this cross-sectional study was conducted on all patients presenting to ed with chief complaint of dyspnea, during 2 years. the patients were asked to describe their dyspnea by choosing three items from the valid and reliable questionnaire or articulating their sensation. the relationship between dyspnea descriptors and underlying cause of symptom was evaluated using spss version 16. results: 312 patients with the mean age of 60.96±17.01 years were evaluated (53.2% male). most of the patients were > 65 years old (48.7%) and had basic level of education (76.9%). “my breath doesn’t go out all the way” with 83.1%, “my chest feels tight” with 45.8%, and “i feel that my airway is obstructed” with 40.7%, were the most frequent dyspnea descriptors in asthma patients. “my breathing requires work” with 46.3%, “i feel that i am suffocating” with 31.5%, and "my breath doesn’t go out all the way" with 29.6%, were the most frequent dyspnea descriptors in copd patients. “my breathing is heavy” with 74.4%, "a hunger for more air” with 24.4%, and “i cannot get enough air” with 23.2%, were the most frequent dyspnea descriptors in chf patients. except for “my breath does not go in all the way”, there was significant correlation between studied dyspnea descriptors and underlying disease (p = 0.001 for all analyses). conclusion: it seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ed suffering from dyspnea. keywords: dyspnea; asthma; pulmonary disease, chronic obstructive; heart failure; symptom assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: sajadi sma, majidi a, abdollahimajd f, jalali f. relationship between dyspnea descriptors and underlying causes of the symptom; a cross-sectional study. emergency. 2017; 5(1): e62. 1. introduction h istory taking and physical examination help clinicians detect the patient’s problem and effectively treat it. dyspnea is a subjective perception of difficulty breathing, commonly seen in patients with respiratory and cardiovascular diseases. healthy subjects may also experience it in intense emotional states and during heavy exercise (1-3). ∗corresponding author: fahimeh abdollahimajd; skin research center, shohadaye tajrish hospital, tajrish square, tehran, iran. email: fabdollahimajd@yahoo.com, tell: 0989132914340, fax: 098-21-22744393 dyspnea is a multidimensional expression, which has been investigated extensively in clinical and psychological settings. usually, it is identified as being unable to take a satisfying deep inspiration; moreover, it is characterized as difficulty breathing, which is described by air hunger and an uneasy awareness of breathing at rest or on exertion (4, 5). as with pain, different terms used to describe the sensation of dyspnea might indicate the underlying diseases (6). previous studies have shown that descriptors are not only different among patients with different disorders but also in those with the same disease. for instance, to describe breathlessness, patients with asthma, prefer terms as “my chest feels tight “and “i cannot get enough air in”, but patients with interstitial lung disease choose the phrase “my this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sma. sajadi et al. 2 breathing is rapid” (7-10). the language used to describe dyspnea may be valuable in identifying the cause of dyspnea and choosing the best treatment modality (10). however, lots of variables such as linguistic and cultural differences can affect the results (6). the present study aimed to evaluate the relationship between different descriptors of dyspnea and underlying cause of the symptom in patients presenting to emergency department (ed) suffering from dyspnea. 2. methods 2.1. study design and setting in this prospective cross-sectional study, all patients presenting to ed of ali-ebne-abitaleb hospital, rafsanjan, iran, with chief complaint of dyspnea, during 2 years, were evaluated regarding the descriptors of dyspnea. the study protocol was approved by ethical committee of rafsanjan university of medical sciences. the patients were informed about all aspects of the research protocol and written informed consent was obtained from the patients. 2.2. participants all patients aged 18 years and older presenting to ed of the mentioned hospital with chief complaint of dyspnea were enrolled using census sampling. cases of communication disability (because of hearing problem, old age, illiteracy) and hemodynamic instability were excluded. subjects were also excluded if an ultimate diagnosis other than congestive heart failure (chf), chronic obstructive pulmonary disease (copd), or asthma was reached. 2.3. data gathering after initial assessment and emergency management, all patients were fully examined and eligible patients were included. a prepared questionnaire containing baseline characteristics and descriptors of dyspnea was used for data gathering. the questionnaire used here has been described in a previously published study (11). the questionnaire was translated into persian language by the researchers and was evaluated in a pilot study, interviewing 20 patients and 5 emergency physicians, to confirm its validity and reliability (cronbach’s alpha for internal consistency = 0.86). to describe dyspnea, two trained medical students asked patients to choose three items from the list. an open ended question was also included allowing patients to describe their sensation if it was not represented in the questionnaire. the patients were categorized into three groups of chf, copd, and asthma based on final diagnosis, which was made based on imaging, spirometry, and other diagnostic tests needed. table 1: baseline characteristics of studied patients variable number (%) age (year) 18 30 16 (5.1) 30 45 36 (11.5) 45 -65 108 (34.6) ≥ 65 152 (48.7) sex male 166 (53.2) female 146 (46.8) level of education basic 240 (76.9) high school 64 (20.5) university 8 (2.6) final diagnosis copd 108 (34.6) asthma 118 (37.9) chf 86 (27.6) chf: congestive heart failure; copd: chronic obstructive pulmonary disease. 2.4. statistical analysis spss software version 16 was used for statistical analysis. mean ± standard deviation or frequency and percentage were used for reporting the results. chi square test was used to analyze relationships between different variables. level of significance was 0.05 with a 95% confidence interval. 3. results 312 patients with the mean age of 60.96±17.01 years (20 88) were evaluated (53.2% male). table 1 shows the baseline characteristics of studied patients. most of the patients were > 65 years old (48.7%) and had basic level of education (76.9%). the patients of all three groups (copd, asthma, chf) were similar regarding age, sex, and level of education (p > 0.05 for all analyses). "my breath doesn’t go out all the way" with 83.1%, “my chest feels tight” with 45.8%, and “i feel that my airway is obstructed” with 40.7%, were the most frequent dyspnea descriptors in asthma patients. “my breathing requires work” with 46.3%, “i feel that i am suffocating” with 31.5%, "my breath doesn’t go out all the way" with 29.6%, were the most frequent dyspnea descriptors in copd patients. "my breathing is heavy" with 74.4%, “a hunger for more air” with 24.4%, and "i cannot get enough air" with 23.2%, were the most frequent dyspnea descriptors in chf patients. table 2 and 3 summarize the relation between different dyspnea descriptors with final diagnosis and level of education, respectively. apart from “my breath does not go in all the way”, there was a significant correlation between studied dyspnea descriptors and final diagnosis (p = 0.001 for all analysis). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e62 table 2: the relationship between different dyspnea descriptors and final diagnosis descriptors diagnosis n (%) p asthma copd chf my breathing is shallow 0 (0) 0 (0) 0 (0) i feel an urge to breathe more 0 (0) 22 (20.4) 16 (18.6) 0.001 my chest is constricted 2 (1.7) 24 (22.2) 16 (18.6) 0.001 my breathing requires effort 2 (1.7) 22 (20.4) 6 (7) 0.001 i feel a hunger for more air 4 (3.4) 0 (0) 21 (24.4) 0.001 i feel out of breath 4 (3.4) 4 (3.7) 14 (16.3) 0.001 i cannot get enough air 0 (0) 0 (0) 20 (23.3) 0.001 my breath does not go in all the way 4 (3.4) 2 (1.9) 4 (4.7) 0.540 my chest feels tight 54 (45.8) 2 (1.9) 0 (0) 0.001 my breathing requires work 20 (16.9) 50 (46.3) 2 (2.3) 0.001 i feel that i am suffocating/smothering 40 (33.9) 34 (31.5) 12 (14) 0.004 i feel that i cannot get a deep breath 2 (1.7) 12 (11.1) 0 (0) 0.001 i feel that i am breathing more 0 (0) 2 (1.9) 8 (9.3) 0.001 my breath does not go out all the way 98 (83.1) 32 (29.6) 6 (7) 0.001 my breathing is heavy 4 (3.4) 2 (1.9) 64 (74.4) 0.001 i feel that my airway is obstructed 48 (40.7) 4 (3.7) 2 (2.3) 0.001 chf: congestive heart failure; copd: chronic obstructive pulmonary disease. table 3: the relationship between different dyspnea descriptors and level of education descriptors level of education n (%) p basic high school university my breathing is shallow 0 (0) 0 (0) 0 (0) i feel an urge to breathe more 34 (14.2) 4 (6.2) 0 (0) 0.129 my chest is constricted 42 (17.5) 0 (0) 0 (0) 0.001 my breathing requires effort 24 (10.0) 6 (9.4) 0 (0.0) 0.639 i feel a hunger for more air 25 (10.4) 0 (0) 0 (0) 0.017 i feel out of breath 16 (6.7) 6 (9.4) 0 (0) 0.552 i cannot get enough air 16 (6.7) 4 (6.2) 0 (0) 0.749 my breath does not go in all the way 8 (3.3) 2 (3.1) 0 (0) 0.870 my chest feels tight 30 (12.5) 22 (34.4) 4 (50.0) <0.001 my breathing requires work 50 (20.8) 20 (31.2) 2 (25.0) 0.212 i feel that i am suffocating/smothering 66 (27.5) 16 (25.0) 4 (50.0) 0.328 i feel that i cannot get a deep breath 12 (5.0) 2 (3.1) 0 (0) 0.670 i feel that i am breathing more 10 (4.2) 0 (0) 0 (0) 0.212 my breath does not go out all the way 86 (35.8) 42 (65.6) 8 (100.0) <0.001 my breathing is heavy 66 (27.5) 4 (6.3) 0 (0) <0.001 i feel that my airway is obstructed 24 (10) 24 (37.5) 6 (75.0) <0.001 4. discussion based on the findings of the present study, patients prefer to use a variety of terminology to describe their sense of dyspnea. there was a significant relationship between the used terms and underlying cause of dyspnea and level of education. "my breath doesn’t go out all the way”, “my breathing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sma. sajadi et al. 4 requires work” , and “my breathing is heavy”, were the most frequent phrases used by asthma, copd, and chf patients, respectively, for description of their respiratory problem. the leading aim of understanding a patient’s dyspnea language is better diagnosis of underlying diseases and consequently increasing therapeutic efficacy. different qualities of dyspnea sensation can point to prominent afferent mechanisms underlying clinical dyspnea making differential diagnosis easier and potentially advocate the best symptomatic therapy. more precise definition of symptoms in patients with shortness of breath has been looked into by researchers in the past. in a study, williams et al. remarked that when the descriptors were not restricted to a single best word or phrase, individuals’ description of feeling breathless could differentiate people with and without a previous diagnosis of copd (8). several studies have shown that dyspnea perception among people is related to diverse etiologies including physiological, psychological, and racial causes and etc. (12-15). some reports have stated that race, sex, educational level and socioeconomic class influence the perception of dyspnea (12-15). barbaro et al. in a study designated that advanced age, airway inflammation, depression status, and severity of asthma affect perception of dyspnea (16). the relationship between dyspnea descriptors and cause of symptom was strongly significant in the present study. in the study conducted by mahler et al, the majority of patients with copd applied work/effort descriptors such as “my breathing requires effort”; on the other hand, “i feel air hunger” had a lower prevalence in these patients (17). in addition, chang et al. showed that the patients with asthma preferred “my chest feels tight” and mostly “work/effort” descriptors were chosen by patients with copd (18). in line with our findings, rutgers et al. showed considerable differences in dyspnea perception between copd and asthma (19). caroci et al. noted that stable copd and chf patients prefer different terms to describe their breathing distress, however, they showed that they may use some similar terms (20). it seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ed suffering from dyspnea. 5. limitation the main limitation of our study was its relatively small sample size, also this study was conducted in a local region of iran and its external validity may be limited. therefore, the results cannot be generalized to the whole of iranian population. hence, further investigations are recommended with larger series to validate the findings. 6. conclusion based on the findings of the present study, patients prefer to use a variety of terminology to describe their sense of dyspnea based on underlying cause of symptom and level of education. it seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ed suffering from dyspnea. 7. appendix 7.1. acknowledgements this article is based on the medical doctoral thesis of dr. fahimeh abdollahimajd and dr. fatemeh jalali in rafsanjan university of medical sciences, rafsanjan, iran. the authors would like to thank dr. ali tabatabaey (department of emergency medicine, qom university of medical sciences) for his critical comments. 7.2. author contribution seyyed mohammad ali sajadi was the lead author and contributed in study design, data gathering and manuscript preparation. alireza majidi was involved in concept development and study design and was involved in manuscript development. fahimeh abdollahimajd was involved in data gathering, data analysis, interpretation, and manuscript preparation and revision. fatemeh jalali was involved in data gathering and interpretation. 7.3. funding/support none. 7.4. conflict of interest none. references 1. mahler da, fierro-carrion g, baird jc. evaluation of dyspnea in the elderly. clinics in geriatric medicine. 2003;19(1):19-33. 2. o’donnell de, banzett rb, carrieri-kohlman v, casaburi r, davenport pw, gandevia sc, et al. pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. proceedings of the american thoracic society. 2007;4(2):145-68. 3. wilcock a, crosby v, hughes a, fielding k, corcoran r, tattersfield ae. descriptors of breathlessness in patients with cancer and other cardiorespiratory diseases. journal of pain and symptom management. 2002;23(3):182-9. 4. yoos hl, kitzman h, mcmullen a, sidora-arcoleo k, anson e. the language of breathlessness: do families and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e62 health care providers speak the same language when describing asthma symptoms? journal of pediatric health care. 2005;19(4):197-205. 5. von leupoldt a, balewski s, petersen s, taube k, schubert-heukeshoven s, magnussen h, et al. verbal descriptors of dyspnea in patients with copd at different intensity levels of dyspnea. chest journal. 2007;132(1):141-7. 6. teixeira ca, rodrigues junior al, straccia lc, vianna edso, silva gad, martinez jab. dyspnea descriptors developed in brazil: application in obese patients and in patients with cardiorespiratory diseases. jornal brasileiro de pneumologia. 2011;37(4):446-54. 7. scano g, stendardi l, grazzini m. understanding dyspnoea by its language. european respiratory journal. 2005;25(2):380-5. 8. williams m, cafarella p, olds t, petkov j, frith p. the language of breathlessness differentiates between patients with copd and age-matched adults. chest journal. 2008;134(3):489-96. 9. yorke j, moosavi sh, shuldham c, jones pw. quantification of dyspnoea using descriptors: development and initial testing of the dyspnoea-12. thorax. 2010;65(1):216. 10. carrieri-kohlman v, donesky-cuenco d, park sk, mackin l, nguyen hq, paul sm. additional evidence for the affective dimension of dyspnea in patients with copd. research in nursing & health. 2010;33(1):4-19. 11. harver a, schwartzstein rm, kotses h, humphries ct, schmaling kb, mullin ml. descriptors of breathlessness in children with persistent asthma. chest journal. 2011;139(4):832-8. 12. hardie ge, janson s, gold wm, carrieri-kohlman v, boushey ha. ethnic differences: word descriptors used by african-american and white asthma patients during induced bronchoconstriction. chest journal. 2000;117(4):935-43. 13. trochtenberg ds, belue r. descriptors and perception of dyspnea in african-american asthmatics. journal of asthma. 2007;44(10):811-5. 14. trochtenberg ds, belue r, piphus s, washington n. differing reports of asthma symptoms in african americans and caucasians. journal of asthma. 2008;45(2):165-70. 15. han j, zhu y, li s, chen x, put c, van de woestijne kp, et al. respiratory complaints in chinese: cultural and diagnostic specificities. chest journal. 2005;127(6):1942-51. 16. barbaro mpf, lacedonia d, palladino gp, bergantino l, ruggeri c, martinelli d, et al. dyspnea perception in asthma: role of airways inflammation, age and emotional status. respiratory medicine. 2011;105(2):195-203. 17. chang a, waterman l, mahler d. prospective assessment of descriptors of dyspnea in chronic obstructive pulmonary disease. am j respir crit care med. 2014;189:a2456. 18. chang as, munson j, gifford ah, mahler da. prospective use of descriptors of dyspnea to diagnose common respiratory diseases. chest journal. 2015; 148 (4): 895902. 19. rutgers s, ten hacken n, koeter g, postma d. borg scores before and after challenge with adenosine 5’monophosphate and methacholine in subjects with copd and asthma. european respiratory journal. 2000;16(3):486-90. 20. de souza caroci a, lareau sc. descriptors of dyspnea by patients with chronic obstructive pulmonary disease versus congestive heart failure. heart & lung: the journal of acute and critical care. 2004;33(2):102-10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e35 ca s e re p o rt acute hepatitis associated with intake of pistacia vera l. bud tea; a case report kazım ersin altınsoy1∗, mehmet murat oktay1 1. department of emergency medicine, ersin arslan training and research hospital, gaziantep islam science and technology university, gaziantep, türkiye. received: february 2023; accepted: march 2023; published online: 29 april 2023 abstract: in this study, a patient who developed acute hepatitis due to drinking pistacia vera l. bud tea is presented. a twentyeight-year-old woman who had just come out of the postpartum period applied to our clinic with complaints of nausea, vomiting, loss of appetite and weakness. blood serum alanine aminotransferase and aspartate aminotransferase levels were increased. all serological tests were negative for viral hepatitis and autoimmune diseases. she had been drinking an herbal tea containing pistacia vera l. bud every day for four weeks to increase milk production. three weeks after discontinuation of herbal tea, liver enzymes returned to normal. based on our knowledge, this is probably the first hepatitis report due to the use of an herbal tea containing pistacia vera l. bud. keywords: chemical and drug induced liver injury; teas, herbal; pistacia; liver failure, acute; plants, medicinal cite this article as: ersin altınsoy k, murat oktay m. acute hepatitis associated with intake of pistacia vera l. bud tea; a case report. arch acad emerg med. 2023; 11(1): e35. https://doi.org/10.22037/aaem.v11i1.2006. 1. introduction plants are used to make traditional medicine. traditional medicines are passed on from generation to generation and their social use continues. most of the society accepts herbal medicines as harmless. however, these products or their metabolites may cause some side effects such as liver damage. according to research data from the usa, approximately 20% of hepatotoxicity cases are caused by herbal nutritional supplements (1). herbal teas have potential add-on effects in lowering blood glucose levels (2, 3). as the use of herbal products increases in europe and the usa, an increase in hepatotoxicity cases is also observed (4, 5). this case report describes a breast-feeding woman who developed acute hepatitis due to drinking an herbal tea containing pistachio bud (figure 1). this is the first report of acute hepatitis related to use of a pistachio bud. this study shows that herbal tea containing pistacia vera l. bud may cause hepatotoxicity that can be clinically confused with other causes of acute hepatitis. clinicians may be faced with a case of acute hepatitis that can∗corresponding author: kazım ersin altınsoy; department of emergency medicine, ersin arslan training and research hospital, gaziantep islam science and technology university, gaziantep, türkiye. email: ersinaltinsoy@gmail.com. tel: +90 532 280 4402, orcid: https://orcid.org/0000-00025707-7645. figure 1: the view of pistacia vera l. (https://www.turktob.org.tr/tr/antepfistigi-yetistiriciligi-vebakimi/4906). not be easily diagnosed, and they should question the patient about the use of herbal medicine. 2. case presentation a twenty-eight-year-old woman, was admitted to the emergency department with symptoms of nausea, vomiting, anorexia, weakness and abdominal discomfort. the physical examination was unremarkable. her medical history was negative for hepatic and metabolic disorders (such as obesity, diabetes mellitus, and atopy). the patient also mentioned that for the past 3-4 weeks she had consumed 2-3 cups of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. altınsoy& m. oktay 2 figure 2: electrocardiography of the patient . home-made herbal tea containing pistacia vera l. daily to increase lactation. the initial laboratory values were: serum aspartate aminotransferase (ast)1766.6 iu/l (reference range [rr] 5–34 iu/l), alanine aminotransferase (alt) 1883 iu/l (rr 3–55 iu/l), yglutamyl transferase (ggt) 374 iu/l (rr 9–36 iu/l), alkaline phosphatase (alp) 347 iu/l (rr 40–150 iu/l), total bilirubin 3.76 mg/dl (rr 0.2–1.2 mg/dl) and conjugated bilirubin 1.95 mg/dl (rr 0.0–0.5 mg/dl). coagulation studies and other laboratory tests, including a complete blood count, serum urea nitrogen, creatinine, glucose, electrolytes, total protein and albumin were normal. results of serological tests for viral hepatitis a, b and c, cytomegalovirus, epstein-barr virus, and type 1 and 2 herpes simplex viruses, as well as serological tests for autoimmune disorders were negative. moreover, serum ceruloplasmin and α1antitrypsin were normal. abdominal ultrasonography showed mild hepatic steatosis and a normal biliary tract. and also electrocardiography was normal (figure 2). the pistacia vera l. bud tea was stopped after admission and the patient was treated conservatively. frequent assessment of the liver function was performed. the patient recovered clinically over the next one week. the patient’s liver function tests returned to normal two weeks later. 3. discussion it is often difficult to identify the exact toxic component of herbal remedies, since they contain multiple ingredients and individual components may not be pure substances. many patients consider herbal remedies as natural and harmless medications, and are turning toward the internet for information regarding their illness and are discovering the potential uses of herbal preparations (6). the true incidence of herbal remedy-induced hepatitis remains unknown because the diagnosis of toxicity induced by an herbal remedy is difficult since there are no specific tests or diagnostic criteria. careful history taking, laboratory findings, and histopathology are used to diagnose toxicity induced by herbal remedies (7-8). physicians and health officials need to warn the public of the potential danger. to prevent severe risks due to the misuse of herbal products, it is very important to raise awareness among the public and healthcare professionals. reporting more cases that involve severe toxicity resulting from the misuse of herbal products may increase awareness of this issue. in light of this, the information about these toxic effects has been provided by case reports, and hence it is difficult to establish a causal relationship. the actual incidence of adverse effects of herbal remedies is not known. the limitation of our case report is that the dose and effect cannot be measured. case series are needed due to the limited number of case reports on this herb. in addition, the inability to establish the relationhips of age, weight, and dose with severity of toxicity is a limiting factor. 4. conclusion the above-described case suggests that herbal tea containing the pistacia vera l. may be a cause of hepatitis, clinically indistinguishable from hepatitis of other etiologies. thus, it highlights the fact that some herbal remedies may not be as safe as they are widely considered. 5. declarations 5.1. acknowledgments the authors thank all those who contributed to this study. 5.2. conflict of interest there is no conflict of interest between the authors or between the authors and other persons-organizations. 5.3. fundings and supports no financial resources other than the authors’ own resources were used in this study. 5.4. authors’ contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.5. ethical consideration and patinets’ consent the ethics committee of faculty of medicine, educational and research hospital, gaziantep islam science and technology university reviewed the medical records and a statement covering patient data confidentiality. the ethics committee did not find it necessary to obtain permission for this research. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e35 references 1. navarro vj, khan i, bjornsson e, seeff lb, serrano j, hoofnagle jh. liver injury from herbal and dietary supplements. hepatology. 2017;65(1):363-73. 2. ahmed b, sultana r, greene mw. adipose tissue and insulin resistance in obese. biomed pharmacother. 2021;137:111315. 3. zhang j, liu m, hu b, wang l. exercise combined with a chinese medicine herbal tea for patients with type 2 diabetes mellitus: a randomized controlled trial. j integr complement med. 2022;28(11):878-86. 4. navarro vj, lucena mi. hepatotoxicity induced by herbal and dietary supplements. semin liver dis. 2014;34(2):17293. 5. clarke tc, black li, stussman bj, barnes pm, nahin rl. trends in the use of complementary health approaches among adults: united states, 2002-2012. natl health stat report. 2015(79):1-16. 6. cardenas a, restrepo jc, sierra f, correa g. acute hepatitis due to shen-min: a herbal product derived from polygonum multiflorum. j clin gastroenterol. 2006;40(7):62932. 7. starakis i, siagris d, leonidou l, mazokopakis e, tsamandas a, karatza c. hepatitis caused by the herbal remedy teucrium polium l. eur j gastroenterol hepatol. 2006;18(6):681-3. 8. ozbek h, ugras s, dulger h, bayram i, tuncer i, ozturk g, et al. hepatoprotective effect of foeniculum vulgare essential oil. fitoterapia. 2003;74(3):317-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e90 rev i ew art i c l e apelin as a candidate for hypertension management; a systematic review and meta-analysis on animal studies mohammad mohammadi1, mobin mohamadi1, amirreza moradi1, hamzah adel ramawad2, pantea gharin1, yaser azizi1,3∗, mahmoud yousefifard1,4 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. department of emergency medicine, nyc health & hospitals, coney island, new york. 3. department of physiology, school of medicine, iran university of medical sciences, tehran, iran. 4. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: august 2022; accepted: september 2022; published online: 7 november 2022 abstract: introduction: hypertension is a medical emergency that requires immediate medical attention. recent studies have suggested that peripheral injection of apelin may lower blood pressure. however, there is no comprehensive conclusion on the role of apelin in treatment of hypertension. the aim of this systematic review was to evaluate the effects of apelin on blood pressure in animal studies. methods: extensive search and data gathering were conducted using keywords related to blood pressure and apelin on medline, embase, scopus, and web of science databases at the end of july 2022. two researchers screened and summarized the articles independently. analysis was then conducted based on apelin dose, route of administration, and follow-up. the findings were reported as standardized mean difference (smd) with a 95% confidence interval (95% ci). results: data from 10 animal studies were included in the present systematic review. time interval between apelin administration and blood pressure assessment was 1 to 21 minutes. findings showed that administration of apelin immediately reduces mean arterial pressure (map) (smd=-3.13; 95% ci: -4.43 to -1.82; p<0.001), systolic blood pressure (sbp) (smd= -1.62; 95% ci: -2.22 to -1.02; p<0.001), and diastolic blood pressure (dbp) (smd= -1.10; 95% ci: -1.59 to -0.62; p<0.001). on follow-up, the effects of apelin on map (meta-regression coefficient=-2.46; p=0.002) and dbp (meta-regression coefficient= -0.16; p=0.012) decreased over time, while the blood pressure lowering effects of apelin on sbp did not change during follow-up (meta-regression coefficient=-0.17; p=0.063). it was also found that by increasing the dose of apelin, dbp and sbp further reduced. these findings suggest that the effect of apelin on sbp (meta-regression coefficient=0.08; p=0.001) and dbp (meta-regression coefficient=0.059; p=0.007) is dose-dependent, and their correlation is significant. conclusion: the present systematic review showed that peripheral administration of apelin immediately reduces map, sbp and dbp in hypertensive animals. in contrast, central administration of apelin increases these parameters. keywords: hypertension; apelin; arterial pressure; blood pressure cite this article as: mohammadi m, mohamadi m, moradi a, ramawad ha, gharin p, azizi y, yousefifard m.apelin as a candidate for hypertension management; a systematic review and meta-analysis on animal studies. arch acad emerg med. 2022; 10(1): e90. https://doi.org/10.22037/aaem.v10i1.1704. ∗corresponding author: yaser azizi; physiology research center, iran university of medical sciences, tehran, iran. tel: +982188622709, email address: azizi.y@iums.ac.ir, orcid: https://orcid.org/0000-0002-0452-7542. † corresponding author: : mahmoud yousefifard; physiology research center, school of medicine, iran university of medical sciences, shahid hemmat highway, tehran 14496-14535, iran. tel: +98 (21) 86704771; email: yousefifard.m@iums.ac.ir, orcid: https://orcid.org/0000-0001-5181-4985. 1. introduction hypertension is a major risk factor for cardiovascular diseases and stroke, two leading causes of death worldwide. it is currently estimated that 1.4 billion (31.1%) people are affected by high blood pressure (1, 2). based on data-driven projections, more than 50 percent of the world’s population will have hypertension within the next 30 years (1-5). this highlights the importance of blood pressure management as one of the most important priorities in health care. risk factors such as obesity, psychological stress, alcohol consumpthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammadi et al. 2 tion, high salt intake, sedentary lifestyle, and genetic predisposition are the leading causes of hypertension (5). because of the multifactorial etiology, alternative modalities should be considered for the management of hypertension. chronic mild inflammation during obesity is a potential risk factor of hypertension (3). inflammation results in the release of adipokines from adipose tissues, which might be associated with hypertension. high blood pressure leads to vascular oxidative stress, which subsequently results in vascular damage, remodeling, fibrosis, and decreased elasticity. as a result, many clinical trials and studies have shown that antioxidant therapies play an important role in the management of hypertension. however, antioxidants such as vitamin c, α-tocopherol (vit e), and flavonoids did not have significant effects of lowering blood pressures (1, 6). discovery of the vasodilatory effects of endogenous peptides such as apelin presents a potential direction of blood pressure management in patients with essential hypertension (7). apelin is a vasoactive endogenous peptide produced from cterminal of a 77-amino acid pre-proapelin. it is cleaved by enzymes to form different apelin fragments (apelin 13, 16, 17, 19, 36). the most active fragment is apelin-13 and its receptor, apj, is a member of the g-protein coupled receptors (8). apelin and apj are widely distributed in the cardiovascular system (9). the apelin-apj signaling is also important for proper development of the cardiovascular system and formation of blood vessels. apelinand apj-knockout mice displayed abnormalities with cardiac contractility, pressure overload, and aging (10). similarly, animals with apelin and apj abnormalities developed spontaneous hypertension (11). in pregnant preeclamptic women, apelin and apj expression in syncytiotrophoblasts and cytotrophoblasts were decreased compared with normotensive control. in animal models with preeclamptic hypertension, treatment with apelin was shown to decrease blood pressure (12-15). it has also been shown that in patients with pulmonary hypertension, apelin and apj expression were decreased. in animal models of hypertension, treatment with apelin was shown to reduce blood pressure (11, 16). although apelin’s ability to temporarily lower blood pressure has been well documented, there are studies that have reported no changes or an increase in blood pressure (9, 15, 17, 18). despite many efforts to study endogenous peptides such as apelin, there is no comprehensive conclusion on apelin’s effects on blood pressure. thus, performing a meta-analysis and systematic review can be helpful for reaching an agreement. the aim of this study was to provide a more precise resource about the effects of apelin on blood pressure. 2. methods 2.1. study design this meta-analysis was designed to evaluate the effects of apelin injection on blood pressure in hypertensive rats and mice. pico was defined as: p; animals (rats and mice) with hypertension through different models, i; apelin injection, c; comparison of apelin-treated hypertensive animals with non-treated hypertensive animals, and o; the outcomes related to blood pressure based on changes in systolic blood pressure (sbp), diastolic blood pressure (dbp), and mean arterial pressure (map). 2.2. selection criteria in this systematic review and meta-analysis, all experimental studies that evaluated the effects of apelin on hypertension and blood pressure were included. since most studies were conducted on rats and mice, we included the same population in our study – without any sex or race/strain limitations. exclusion criteria included studies without a control group, and studies that did not report desired data, including blood pressure level, type, or time of the apelin injection. also excluded were duplicate studies, review studies, human studies, and in-vitro studies. 2.3. search strategy two reviewers separately conducted extensive search on medline (via pubmed), isi web of science, embase, and scopus in july 2022. the keywords used in searches were words related to blood pressure and apelin. keywords were selected as widely as possible so that no suitable study would be missed (appendix 1). although only animal studies were included in the present meta-analysis, the animal studies filter (from the online databases) was not used in the search strategy. this was done in order not to miss any related studies since the online databases cannot always correctly differentiate between animal and human studies. keywords used in the search strategy were obtained using mesh section of pubmed database, emtree network of embase database, and search in related article titles. consulting with specialists in the field of hypertension was another method used to finalize the keywords. to find additional articles or unpublished data, manual search was performed in the bibliography of relevant studies and related articles. on the other hand, for searching in gray literature, three strategies have been followed. first, searching proquest database for dissertations; second, contacting the authors of related articles to access unpublished or forthcoming data; and third, using google and google scholar search engines to find more literature. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e90 2.4. data gathering search in the mentioned databases was conducted and duplicate articles were removed, then two researchers started screening the articles independently. in the first step, the selection of articles was based on the title and abstract obtained from the databases, and in the second step, full text of possibly related articles was studied to select all related articles. all steps were accomplished separately by two researchers and in cases of disagreement the dispute was resolved through consultation with a third researcher. data extracted from articles included in this systematic search were recorded in a checklist designed based on preferred reporting items for systematic reviews and meta-analyses (prisma) statement guidelines. extracted data included information related to the study design, the characteristics of all the samples (age, weight, sex, model of inducing hypertension), administration protocol, administration route (peripheral or central), number of samples studied, investigated outcomes (mean arterial pressure, systolic blood pressure, diastolic blood pressure), and follow-up duration. since most experimental studies use graphs to report their findings; whenever necessary, data were extracted using plot digitizer. 2.5. risk of bias assessment quality control of the articles was performed using a checklist designed based on systematic review centre for laboratory animal experimentation (syrcle)’s risk of bias tool for animal studies (19). in cases of disagreement the dispute was resolved through consultation with a third researcher. 2.6. statistical analysis to conduct analysis, mean standard deviation of recorded data and number of samples in each group was recorded in stats 14.0 statistical software. then, using the ‘metan’ command in this software, standardized mean difference (smd) with a 95% confidence interval (ci) was calculated for each group. and finally, a pooled effect size was reported. heterogeneity was evaluated based on i2. either random effect model’ or ‘fix effect model’ was used based on heterogeneity. since apelin dose, follow-up duration, and administration protocol (peripheral or central) varied between different studies, studies were divided based on these variables and then analysis was performed. it is worth mentioning that ‘funnel plot’ was used to identify publication bias using the egger’s test (20). 3. results the systematic search resulted in 1338 non-duplicate articles. after screening titles and abstracts, 28 articles were reviewed in detail. ten articles (18, 21-29) were included in the present meta-analysis (figure 1). all 10 of these studies were conducted on rats. apelin-13 was used in 8 studies, apelin12 in 1 study, and apelin-36 in 1 study. the route of apelin administration in 8 studies was peripheral, 7 of them intravenous and 1 of them intraperitoneal. in the two remaining studies, the administration route was central. model of hypertension induction was as follows: l-name injection in 3 articles, two-kidney-one-clip (2k1c) model in 3 articles, angiotensin ii injection in 2 articles, and doca-salt injection in 1 article. in 1 article, spontaneously hypertensive rats were used. follow-up duration varied from 0 minute to 21 days. two articles measured blood pressure noninvasively, using tail cuff. the remaining 8 articles measured arterial pressure invasively by placing a catheter in the carotid artery. induced hypertension in 3 articles was acute, while in the other 7 it was chronic (table 1). 3.1. meta-analysis effect of apelin administration on mean arterial pressure (map) in our analysis, studies were divided into two groups based on apelin administration route: 1) peripheral injection and 2) central injection. results of statistical analysis showed that peripheral apelin injection decreases map (smd=-3.13; 95% ci: -4.43 to -1.82; p<0.001), while central apelin injection results in map elevation (smd=3.55; 95% ci: 2.43 to 4.67; p<0.001) (fig. 2). in the evaluation of the effect of total injected dose of apelin on map, it was found that map does not alter with change in dose of apelin, and there is no significant relationship between dose and beneficial effects of apelin on map (meta-regression coefficient=0.11; p=0.454) (fig. 5). on the other hand, according to the results of statistical analysis, by continuing the follow-up process, the effect of apelin on map decreases over time (meta-regression coefficient=-2.46; p=0.002). effect of apelin administration on systolic blood pressure (sbp) as mentioned, the studies were divided into two groups based on apelin administration route: 1) peripheral injection and 2) central injection. results of statistical analysis showed that peripheral apelin injection decreases sbp (smd=-1.62; 95% ci: -2.22 to -1.02; p<0.001), while central apelin injection results in sbp elevation (smd=5.13; 95% ci: 1.86 to 8.41; p=0.008) (fig. 3). in the evaluation of the effect of total injected dose of apelin on sbp, it was found that with increase in dose of apelin, sbp is further reduced, which suggests that its effect on sbp is dose-dependent, and their relation is significant (meta-regression coefficient=0.08; p=0.001) (fig. 5). on the other hand, based on our statistical analysis, by continuing the follow-up process -and recording the changes in sbpthe effect of apelin does not significantly change over time (meta-regression coefficient=-0.17; p=0.063). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammadi et al. 4 effect of apelin administration on diastolic blood pressure (dbp) results of statistical analysis also showed that peripheral apelin injection decreases dbp (smd=-1.10; 95% ci: -1.59 to -0.62; p<0.001), while central apelin injection results in dbp elevation (smd=4.09; 95% ci: 2.11 to 6.07; p= 0.089) (fig. 4). in the evaluation of the effect of total injected dose of apelin on dbp, it was found that with increase in dose of apelin, dbp is further reduced, which suggests that its effect on dbp is dose-dependent, and their relation is significant (meta-regression coefficient=0.059; p=0.007) (fig. 5). based on the results of statistical analysis, by continuing the followup process, the effect of apelin on dbp decreases over time (meta-regression coefficient=-0.16; p=0.012). publication bias assessment in publication bias assessment of the present study, it was revealed that there was no evidence of publication bias in any of the studied parameters including: the relation between apelin administration and 1) mean arterial pressure (p<0.124), 2) systolic blood pressure (p=0.458) and 3) diastolic blood pressure (p=0.181). 4. discussion results of our analyses indicate that peripheral apelin administration decreases map, sbp and dbp, while central administration increases these parameters. statistical analysis also shows that increasing dose of administration causes further reduction in sbp and dbp, but no significant change is seen in its effect on map. when apelin administration was continuous, its effects persisted during follow-up. the mechanisms by which apelin changes blood pressure is not fully understood. studies have shown that apelin has a transient effect on blood pressure, which starts less than one minute after intravenous injection and can last up to 3-4 minutes before the blood pressure returns to its prior level (17, 22, 30-34). in contrast, it has been shown that apelin micro-injection in the rostral ventrolateral medulla (rvlm) increases neural activity in this region, which in turn increases sympathetic activity and causes vasoconstriction that results in blood pressure elevation (35). studies on the mechanism of vasodilatory effects of apelin, when administered peripherally, have shown that apelin increases the production of no through increasing enos expression. as a result, apelin dilates blood vessels through the endotheliumdependent pathway (36). as previously mentioned, the apelin administration was divided into two groups: 1) peripheral administration, and 2) central administration. results show that peripheral administration decreases map, while central administration increases map. our findings show that the effect of apelin on map did not change with changing the dose of apelin and no significant relationship was observed between dose and its effects. based on statistical findings, with continuing the follow-up process and recording the changes in blood pressure after the last administration, effect of apelin diminishes over time. it appears that apelin exerts short-term effects by increasing the production of no, and in the case of intraventricular injection, it increases blood pressure by increasing vasopressin production and sympathetic vasoconstrictor activity. it was shown that the administration of apelin reduces sbp in the peripheral administration, while it increases sbp in the central route of administration. studying the effect of total prescribed dose of apelin on sbp revealed that by increasing the dose of apelin, sbp is further reduced, and a significant relationship was observed between the dose and its effects. additionally, our results indicate that by continuing the follow-up process and recording sbp after treatment with apelin, the effect of apelin does not change over time. from these findings, it can be inferred that the effectiveness of apelin on sbp is not affected by time, but is more dosedependent. this means that increasing the dose of apelin further reduces sbp. since p-value was close to the significance level, it is feasible that future studies can prove its effectiveness. since apelin increases myocardial contractility, it may elevate sbp. however, the activation of baroreceptors in aortic arch and carotid sinus subsequently decreases sbp. apelin increases production of no, which decreases sbp and thus, decreases cardiac afterload. most likely, the duration of administration should be longer to exert long-term effects. since apelin decreases map, it makes sense that apelin also reduces sbp by improving vasodilation. another indicator discussed in most of the studies was dbp. peripheral apelin administration increases dbp and its central administration decreases it. the effect of apelin on dbp was dose-dependent, which means higher doses cause further reduction in dbp and it was statistically significant. according to the obtained results, continuation of the follow-up process and recording changes in dbp shows that the effectiveness of apelin continues over time. in the present research, none of the studied indicators, including the relationship between apelin administration with map, sbp and dbp, showed evidence of publication bias so it can be concluded that apelin is effective for controlling blood pressure. experts believe that a suitable medication to control blood pressure crisis should reduce blood pressure by 10 to 15% in the first hour and lead to an extra 10 to 15% decrease in the subsequent 4 hours to prevent hypoperfusion complications. although, apelin, as a rapid-onset medication, can decrease bp in a few minutes, its optimum dose for treating hypertension is not known. therefore, we strongly recommend that future studies identify a dose of apelin that can reduce blood pressure by 10-15% during the first hour. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e90 5. limitation one of the most important limitations of the current study is presence of risk of bias in the included studies. lack of reporting required data in the eligible studies for passing judgment about random sequence generation, allocation concealment, random housing, random outcome assessment, blinding of observers, incomplete outcome data, and selective outcome reporting are the main sources of high risk of bias. these items are generally not reported in experimental studies, and shows one of the basic problems in reporting of preclinical evidence. another limitation of the current meta-analysis was the wide variation in the doses of apelin prescribed in the studies. although the variation in the prescribed dose was not a source of heterogeneity, several doses of this drug should be compared in future studies (dose-response gradient) and finally, the optimum dose should be suggested. 6. conclusion the present systematic review of preclinical evidence showed that peripheral administration of apelin reduces map, sbp and dbp in hypertensive animals. on the other hand, central administration of apelin increases these parameters. 7. declarations 7.1. acknowledgments not applicable. 7.2. ethics approval not applicable. 7.3. patient consent not applicable. 7.4. informed consent not applicable. 7.5. availability of data and materials all data generated or analyzed during this study are included in this published article and its supplementary information file. 7.6. permission to reproduce material from other sources not applicable. 7.7. conflicting interests the authors declare that they have no competing interests. 7.8. funding this research was supported by iran university of medical sciences (grant no: 16713). 7.9. author contributions ideation and design: my, and ya. data collection: mm, mm, am, pg, har. analysis: my. drafting the work: my, ya, mm. revising draft critically for important intellectual content: all authors. the authors read and approved the final manuscript. references 1. ahmad ka, yuan yuan d, nawaz w, ze h, zhuo cx, talal b, et al. antioxidant therapy for management of oxidative stress induced hypertension. free radic res. 2017;51(4):428-38. 2. egan bm, kjeldsen se, grassi g, esler m, mancia g. the global burden of hypertension exceeds 1.4 billion people: 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28. zhao y, li y, li z, xu b, chen p, yang x. superoxide anions modulate the performance of apelin in the paraventricular nucleus on sympathetic activity and blood pressure in spontaneously hypertensive rats. peptides. 2019;121:170051. 29. zhang f, sun hj, xiong xq, chen q, li yh, kang ym, et al. apelin-13 and apj in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats. acta physiol (oxf ). 2014;212(1):17-27. 30. japp ag, newby de. the apelin-apj system in heart failure: pathophysiologic relevance and therapeutic potential. biochem pharmacol. 2008;75(10):1882-92. 31. kleinz mj, davenport ap. emerging roles of apelin in biology and medicine. pharmacol ther. 2005;107(2):198-211. 32. hashimoto t, kihara m, ishida j, imai n, yoshida s, toya y, et al. apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells. arterioscler thromb vasc biol. 2006;26(6):1267-72. 33. reaux-le goazigo a, morinville a, burlet a, llorenscortes c, beaudet a. dehydration-induced crossregulation of apelin and vasopressin immunoreactivity levels in magnocellular hypothalamic neurons. endocrinology. 2004;145(9):4392-400. 34. reaux a, gallatz k, palkovits m, llorens-cortes c. distribution of apelin-synthesizing neurons in the adult rat brain. neuroscience. 2002;113(3):653-62. 35. yao f, modgil a, zhang q, pingili a, singh n, o’rourke st, et al. pressor effect of apelin-13 in the rostral ventrolateral medulla: role of nad(p)h oxidase-derived superoxide. j pharmacol exp ther. 2011;336(2):372-80. 36. salcedo a, garijo j, monge l, fernandez n, luis garciavillalon a, sanchez turrion v, et al. apelin effects in human splanchnic arteries. role of nitric oxide and prostanoids. regul pept. 2007;144(1-3):50-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e90 table 1: characteristics of included studies author; year gender; species; strain; age dose (nmol/kg) / total number of administration / number administration/day / route interval time between induction of bp to treatment (minutes) model of htn induction / dose of inducer / type of htn method of bp assessment followup akcilar; 2013 male; rat; wistar albino; 8–10-wk 200 / 17 / 1 / ip 24 doca-salt treatment / 25 mg/kg / chronic tail cuff bp 17 days ishida; 2004 male; rat; wky shr; 12-wk 3, 6, 15 / 1 / 1 / iv 0.25 l-name / 10 mg/kg / acute intra-arterial catheter 5 minutes lee; 2005 male; rat; shr wistar; approximately 15-wk 15 / 1 / 1 / iv 0 angiotensin ii / 30 ng/kg / acute intra-arterial catheter 1, 5, 10 minutes rostamzadeh; 2018 nr; rat; wistar; nr 40, 60 / 1 / 1 / iv 2688 2k1c / na / chronic intra-arterial catheter 1, 5, 10 minutes siddiquee; 2011 male; mouse; c57bl/6j; 8-wk 15 / 21 / 1 / iv 504 l-name, angiotensin ii / 1.0 mg/ml drinking water, 1.0 µg/kg/day / chronic tail cuff bp 21 days soltanihekmat; 2011 male; rat; sprague–dawley; nr 10, 20, 40/ 1 / 1 / iv 672 2k1c / na / chronic intra-arterial catheter 1, 5, 10 minutes tatemoto; 2001 male; rat; wistar; 89-wk 7, 8, 20 / 1 / 1 / iv 0.16 l-name / 30 mgr per kg / acute intra-arterial catheter 1, 4 minutes yeganehhajahmadi; 2017 male; rat; wistar; nr 20, 40 / 1 / 1 / iv 672 2k1c / na / chronic intra-arterial catheter 1, 4, 10 minutes zhang; 2014 male; rat; wky shr; 13-wk 4, 45, 450 / 15 / 1 / in pvn 0 shr rats / na / essential intra-arterial catheter 1 minute zhao; 2018 male; rat; wky shr; 13-wk 4, 450 / 1 / 1 / in pvn 0 shr rats / na / essential intra-arterial catheter 1 minute 2k1c: 2 kidneys one clip; bp: blood pressure; htn: hypertension; ip: intraperitoneal; iv: intravenous; doca: deoxycorticosterone acetate; l-name: l-ng-nitro arginine methyl ester; na: not applicable; nr: not reported; pvn: paraventricular nucleus; shr: spontaneous hypertensive rat; wky: wistar kyoto; wk: weeks. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammadi et al. 8 table 2: risk of bias assessment among the studies based on syrcle’s tool domain sequence generation baseline characteristics allocation concealment random housing blinding of caregivers random outcome assessment blinding of observers incomplete outcome data selective outcome reporting other sources akcilar; 2013 low risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk ishida; 2004 high risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk lee; 2005 high risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk rostamzadeh; 2018 low risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk siddiquee; 2011 high risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk soltanihekmat; 2011 low risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk tatemoto; 2001 high risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk yeganehhajahmadi; 2017 low risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk zhang; 2014 low risk low risk high risk high risk not reported high risk not reported not reported cannot be determined low risk zhao; 2018 high risk low risk high risk high risk not reported high risk not reported low risk cannot be determined low risk syrcle: systematic review centre for laboratory animal experimentation. figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flow diagram of the present meta-analysis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e90 figure 2: forest plot of effect of apelin on mean arterial pressure based on central and peripheral routes for administration of apelin. smd: standard mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammadi et al. 10 figure 3: forest plot of effect of apelin on systolic blood pressure based on central and peripheral routes for administration of apelin. smd: standard mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e90 figure 4: forest plot of effect of apelin on diastolic blood pressure based on central and peripheral routes for administration of apelin. smd: standard mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammadi et al. 12 figure 5: meta regression analysis of effect of peripheral apelin administration on blood pressure based on dose of apelin and follow-up duration. smd: standard mean difference. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e90 figure 6: publication bias in assessment of the effect of apelin administration on blood pressure. smd: standard mean difference. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2017; 5 (1): e79 or i g i n a l re s e a rc h intranasal lidocaine for primary headache management in emergency department; a clinical trial hassan barzegari1, hassan motamed1∗, behrad ziapour1, majid hajimohammadi1, mina kadkhodazadeh1 1. emergency medicine department, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: august 2017; accepted: august 2017; published online: 16 september 2017 abstract: introduction: most of the headache cases only require pain management in emergency department (ed). the present study aimed to evaluate the efficacy of intranasal lidocaine in this regard. methods: in this clinical trial, adult patients with primary headache were randomly treated with 7.5 mg intravenous (iv ) chlorpromazine and 1 ml intranasal lidocaine 2% (treatment) or normal saline 0.9% (placebo), and were compared 5, 15, and 30 minutes later regarding success rate using spss 21. results: 100 patients were assigned to either treatment or placebo group. number needed to treat of intranasal lidocaine at 5, 15, and 30 minutes were 4 (95% ci: 2.2 – 6.6), 3 (95% ci: 1.7 – 3.5), and 4 (95% ci: 2.3 – 15.9), respectively. these measures for absolute risk reduction were 30 (95% ci: 15.2 – 44.8), 44 (95% ci: 28.7 – 59.3), and 26 percent (95% ci: 6.3 – 44.3), respectively. pain relapse occurred in 16% of treatment and 11% of control group within 1 hour of treatment (p = 0.402). conclusion: it seems that, intranasal lidocaine along with iv chlorpromazine could result in more successful and faster management of primary headaches in ed. keywords: pain management; tension-type headache; administration, intranasal; lidocaine; migraine disorders © copyright (2017) shahid beheshti university of medical sciences cite this article as: barzegari h, motamed h, ziapour b, hajimohammadi m, kadkhodazadeh m. intranasal lidocaine for primary headache management in emergency department; a clinical trial. emergency. 2017; 5(1): e79. 1. introduction h eadache is a common cause of emergency department (ed) visits. most of these patients only require symptomatic treatment and referral to a neurologist or the patient’s family physician on an outpatient basis (1). migraine, tension, and cluster are three types of primary headaches with considerable clinical overlap, which suggests the same pathophysiology (1). common drugs used to treat these headaches are intravenous (iv ) and oral opioids, ergot alkaloids, antiemetic, and non-steroidal anti-inflammatory drugs (nsaids) (2, 3). intranasal route of drug administration may be more effective than other routes, with lower chance of emesis, and a quicker onset of action (3). intranasal delivery of zolmitriptan, civamide, cocaine, and sumatriptan has been tried for treatment of migraine and cluster headaches (4-7). lawrence robbins showed the safety of intranasal lidocaine ∗corresponding author: hassan motamed; emergency department, golestan hospital, golestan avenue, ahvaz, khuzestan province, iran. postal code: 6135733118 tel/fax: +986133743099 email: hasan_motamed@yahoo.com as a an adjunctive medication in cluster headache control (8). studies have reported that nasal lidocaine decreased cluster and migraine headaches within several seconds to 2 minutes (9, 10). however, blanda and their colleagues didn’t find any evidence that supports the mentioned issue (11). there has been limited experiences regarding primary headache management through intranasal medication in ed. therefore, this study aimed to evaluate the efficacy of intranasal lidocaine in primary headache management in ed. 2. methods 2.1. study design and setting this randomized, double blind placebo controlled trial was done on patients presenting to emergency department of golestan hospital, ahwaz, iran, from july 2012, to december 2014 with primary headache (migraine, cluster or tension). the study design was approved by ethics committee of ahvaz jundishapur university of medical sciences under the number u-91159 and registered on iranian registry of clinical trials under this number: irct201212289148n2. written informed consent was obtained from all patients. researchers adhered to declaration of helsinki protocol and confidentialthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. barzegari et al. 2 figure 1: pain severity at the baseline and 5, 15, and 30 minutes after treatment in lidocaine and placebo groups based on visual analogue scale (vas). ity of patients’ information. 2.2. participants the subjects were patients between 15 – 55 years old who presented to the emergency department with complaints of primary headaches (migraine, cluster, or tension) according to the definition of international headache society and ad hoc committee on classification of headache. patients with signs of secondary headaches such as fever, meningismus, trauma, unstable vital signs, and altered mental status were excluded. lactating and pregnant women as well as who had taken analgesic medications 2 hours before referring to ed were also excluded. participants were randomly assigned to either treatment or control group using simple random sampling method. 2.3. intervention patients in the treatment group received 1 ml intranasal lidocaine 2% (20 mg lidocaine) and 7.5 mg intravenous (iv ) chlorpromazine and those in control group received 1 ml intranasal normal saline 0.9% and 7.5 mg iv chlorpromazine. the lidocaine and normal saline were sprayed with the same shape and color containers. 2.4. data gathering a checklist that consisted of baseline characteristics (sex, age), type of primary headache, pain severity, and possible complications was filled for all patients by a senior emergency medicine resident under supervision of an emergency medicine physician. visual analog scale (vas) was used to rate the pain severity at the baseline as well as 5, 15, and 30 minutes after drug administration. in addition, patients were observed for an additional 30 minutes to assess whether they responded to the treatment or whether their pain returned. patients, in charge physicians, and data analyzer were blinded to drugs given to each group. 2.5. outcome 5, 15, and 30 minute success rates were considered as the main outcome of the study. 2.6. statistical analysis considering 95% confidence interval (ci), 80% power, and according to the maizals et al. and blanda et al. findings (11, 12), the minimum sample size for each study group was calculated to be 50 cases. data analysis (intention to treat analysis) was performed by the statistical package for social sciences (spss) version 21. findings were presented as mean ± standard deviation or frequency and percentage. student t test, anova and chi square or fisher’s exact tests were used for comparisons. success was defined as an at least 3 points decrease of pain severity (based on vas) 5, 15, or 30 minutes after treatment. p < 0.05 was considered as significant. 3. results 3.1. baseline characteristics 100 patients were randomly assigned to either treatment (50 cases) or control (50 cases) group (54.0% female). the mean age of treatment and control groups were 32.96 ± 8.51 and 29.60 ± 8.64 years, respectively (p = 0.050). table 1 shows the baseline characteristics of studied patients. 3.2. pain control the mean pain severity of patients at the time of presenting to emergency department and 5, 15, and 30 minutes after treatment are summarized in table 2 and figure 1. the success rates of two groups at 5, 15, and 30 minutes are compared in table 3. there was not any significant correlation between success rate and sex (p = 0.292), age (p = 0.380), and type of headache (p = 0.489). number needed to treat of intranasal lidocaine at 5, 15, and 30 minutes were 4 (95% ci: 2.2 – 6.6), 3 (95% ci: 1.7 – 3.5), and 4 (95% ci: 2.3 – 15.9), respectively. these measures for absolute risk reduction were 30 (95% ci: 15.2 – 44.8), 44 (95% ci: 28.7 – 59.3), and 26 percent (95% ci: 6.3 – 44.3), respectively. the side effects related to treatment were not apparent in either the treatment or the control group within 30 minutes after treatment. pain relapse occurred in 16% of the treatment and 11% of the control group during 1 hour follow up (p = 0.402). 4. discussion considering 30, 44, and 26 percent absolute risk reduction at 5, 15, and 30 minutes after treatment, intranasal lidocaine along with intravenous chlorpromazine could result in more this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e79 table 1: baseline characteristics of the two studied groups variable group n (%) p value intranasal lidocaine placebo sex male 22 (44.0) 24 (48.0) 0.688 female 28(56.0) 26 (52.0) age (year) 20 – 29.9 20 (40.0) 31 (62.0) 30 – 39.9 10 (20.0) 10 (20.0) 0.038 ≥ 40 20 (40.0) 9 (18.0) type of headache migraine 16 (32.0) 22 (44.0) tension 11 (22.0) 18 (36.0) 0.028 cluster 23 (46.0) 10 (20.0) table 2: pain severity of two studied groups based on visual analogue scale time (minute) groups p value intranasal lidocaine placebo baseline 6.15 ± 1.19 5.87 ± 1.01 0.225 5 4.56 ± 1.54 5.30 ± 1.29 0.011 15 3.86 ± 1.57 4.76 ± 1.09 0.001 30 2.94 ± 1.63 3.94 ± 1.52 0.002 table 3: success rate of the two studied groups 5, 15, and 30 minutes after treatment time (minute) group n (%) p value intranasal lidocaine placebo 5 18 (36) 3 (6) < 0.0001 15 25 (50) 3 (6) < 0.0001 30 30 (60) 17 (34) 0.009 successful pain management of primary headaches in ed. this study showed that patients who received intranasal lidocaine along with iv chlorpromazine significantly experienced higher success rate in pain control at 5, 15, and 30 minutes after treatment. although the two studied groups had different baseline characteristics, the analysis of data didn’t show any relationship between age, sex, and type of primary headache with treatment success rate. maizels and geiger evaluated the efficacy of intranasal lidocaine in a double-blind controlled trial with open-label follow-up. they found that headache was relieved within 15 min in 35.8% of patients in the treatment group, with a 20.6% relapse rate (12). mohammadkarimi and colleagues using intranasal lidocaine in 90 patients with primary and secondary headaches found significant pain relief after 1 minute, and showed that the level of patients’ pain did not significantly change over the course of the study. they did not assess the relapse rates or side effects related to treatment (9). in contrast, blanda and colleagues found that the intranasal lidocaine did not relieve pain after 5 or 30 minutes (11). although the experience of drug delivery through nasal mucosa goes back to many years ago, based on a review in 2013 the present method for delivering the drug to the posteriorsuperior part of the nose is not that effective and this could affect the success rate of this method to a great extent (13). it seems that using a new method that can be applied by the patients themselves without the need for visiting the hospital should be considered more seriously. this is of great importance, especially for cases such as primary headaches that are usually recurrent and distractive. of course, there is still a long way to go in making the use of these drugs public and revising traditional methods. 5. limitation in the current study, we administered intranasal 2% lidocaine for different types of headache and not just for migraine. we followed patients in both the treatment and control groups for only a short time. we did not perform follow-up assessments. in addition, because our treatment group received lidocaine and chlorpromazine together, our study is limited this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. barzegari et al. 4 in its assessment of pure lidocaine’s ability in pain management. 6. conclusion considering 30, 44, and 26 percent absolute risk reduction at 5, 15, and 30 minutes after treatment, intranasal lidocaine along with iv chlorpromazine could result in more successful and faster management of primary headaches in ed. 7. appendix 7.1. acknowledgements the cooperation of golestan hospital, ahvaz, staff members is appreciated. 7.2. author contribution all the authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. go s. nontraumatic headaches in the emergency department: a systematic approach to diagnosis and controversies in two" big ticket" entities. missouri medicine. 2008;106(2):156-61. 2. edvinsson l. pathophysiology of primary headaches. current pain and headache reports. 2001;5(1):71-8. 3. rapoport am, bigal me, tepper sj, sheftell fd. intranasal medications for the treatment of migraine and cluster headache. cns drugs. 2004;18(10):671-85. 4. van vliet j, bahra a, martin v, ramadan n, aurora s, mathew n, et al. intranasal sumatriptan in cluster headache randomized placebo-controlled double-blind study. neurology. 2003;60(4):630-3. 5. cittadini e, may a, straube a, evers s, bussone g, goadsby pj. effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebocontrolled, double-blind crossover study. archives of neurology. 2006;63(11):1537-42. 6. diamond s, freitag f, phillips s, bernstein j, saper j. intranasal civamide for the acute treatment of migraine headache. cephalalgia. 2000;20(6):597-602. 7. costa a, pucci e, antonaci f, sances g, granella f, broich g, et al. the effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache. cephalalgia. 2000;20(2):85-91. 8. robbins l. intranasal lidocaine for cluster headache. headache: the journal of head and face pain. 1995;35(2):83-4. 9. mohammadkarimi n, jafari m, mellat a, kazemi e, shirali a. evaluation of efficacy of intra-nasal lidocaine for headache relief in patients refer to emergency department. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2014;19(4):331. 10. generali j, cada dj. intranasal lidocaine: migraine headaches. hospital pharmacy. 2001;36(2):192-223. 11. blanda m, rench t, gerson lw, weigand jv. intranasal lidocaine for the treatment of migraine headache: a randomized, controlled trial. academic emergency medicine. 2001;8(4):337-42. 12. maizels m, geiger am. intranasal lidocaine for migraine: a randomized trial and openâăřlabel followâăřup. headache: the journal of head and face pain. 1999;39(8):543-51. 13. djupesland pg, messina jc, mahmoud ra. breath powered nasal delivery: a new route to rapid headache relief. headache: the journal of head and face pain. 2013;53:72-84. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1); e73 or i g i n a l re s e a rc h the relationship of st segment changes in lead avr with outcomes after myocardial infarction; a cross sectional study mohammad reza beyranvand1, mohammad assadpour piranfar1, mohammadreza mobini2, mehdi pishgahi2∗ 1. department of cardiology, taleghani hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of cardiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2017; accepted: june 2017; published online: 30 june 2017 abstract: introduction: among the 12 leads studied in electrocardiography (ecg), lead avr can be considered as the most forgotten part of it since no attention is paid to it as the mirror image of other leads. therefore, the present study has been designed with the aim of evaluating the prevalence of st segment changes in lead avr and its relationship with the outcome of these patients. methods: in this retrospective cross sectional study medical profiles of patients who had presented to emergency department with the final diagnosis of myocardial infarction (mi) in a 4-year period were evaluated regarding changes of st segment in lead avr and its relationship with in-hospital mortality, the number of vessels involved, infarct location and cardiac ejection fraction. results: 288 patients with the mean age of 59.00 ± 13.14 (18 – 91) were evaluated (79.2% male). 168 (58.3%) patients had the mentioned changes (79.2% male). there was no significant relationship between presence of st changes in lead avr with infarct location (p = 0.976), number of vessels involved (p = 0.269) and ejection fraction on admission (p = 0.801). however, st elevation ≥ 1 mv in lead avr had a significant relationship with mortality (odds = 7.72, 95% ci: 3.07 – 19.42, p < 0.001). sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of st elevation ≥ 1 for prediction of in-hospital mortality were 41.66 (95% ci: 22.79 – 63.05), 91.53 (95% ci: 87.29 – 94.50), 31.25 (95% ci: 16.74 – 50.13), 94.44 (95% ci: 90.65 – 96.81), 0.45 (95% ci: 0.25 – 0.79), and 0.05 (95% ci: 0.03 – 0.09), respectively. conclusion: based on the results of the present study, the prevalence of st segment changes in lead avr was estimated to be 58.3%. there was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. however, presence of st elevation ≥ 1 in lead avr was associated with 8 times increase in in-hospital mortality risk. keywords: myocardial infarction; electrocardiography; patient outcome assessment; st elevation myocardial infarction © copyright (2017) shahid beheshti university of medical sciences cite this article as: beyranvand m, assadpour piranfar m, mobini m, pishgahi m. the relationship of st segment changes in lead avr with outcomes after myocardial infarction; a cross sectional study. emergency. 2017; 5(1): e73. 1. introduction c hest pain caused by myocardial infarction (mi) is among the most common causes of patients visiting emergency departments (eds). there has been a prediction of 80% increase in cases affected with problems related to coronary arteries in developing countries such as ∗corresponding author: mehdi pishgahi; cardiology department, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. email: mp_cr1@yahoo.com tel/fax: 00989123387486 india, latin america region, middle east, and african sahara by 2020 (1, 2). predicting the outcome of these patients can be helpful in more proper triage, giving information to their relatives, and more accurate care for the more severe cases. the final outcome of these patients depends on various factors such as age, size and place of the infarction, residual left ventricular function, presence of underlying illnesses, and delay in reperfusion of affected arteries (3-6). numerous studies have been done regarding the relationship between electrocardiogram (ecg) evidence with angiography findings and final outcome of these patients and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. beyranvand et al. 2 among them, st segment changes in lead avr has been associated with poor outcome of patients with mi during their hospitalization period (7-9). in a study by kukla et al. patients who had st-elevation in lead avr, faced in hospital death 1.5 times those with st-depression and about 30 times those without changes in st segment (10). in addition, findings of senaratne et al. revealed that mortality rate was 16 times higher in patients who had mi with st depression in lead avr (11). they expressed that although st segment depression in lead avr is difficult to diagnose, it can be good evidence of ischemia or injury to apex and infrolateral regions of the heart. presence of st segment depression is indicative of a larger area on the cardiac muscle being involved and somehow shows the need for more invasive interventions (12, 13). additionally, st elevation in lead avr has been associated with increased probability of recurrent infarction, developing cardiac failure and increased need for bypass surgery of coronary arteries (12). a study by kosuge et al., indicated 78% sensitivity and 86% specificity of more than 0.05 mv st segment elevation in avr lead for predicting involvement of all 3 cardiac vessels (14). until now, no similar studies have been carried out on iranian patients in this field; therefore, the present study has been designed with the aim of evaluating the relationship of st segment elevation in lead avr with the final outcome of the patients with mi presenting to ed. 2. methods 2.1. study design in this retrospective cross sectional study medical profiles of patients who were hospitalized in taleghani hospital, tehran, iran, during the time between 2012 and 2015 with the final diagnosis of mi were evaluated with the aim of assessing the prevalence of st segment changes in lead avr and its relationship with the outcome of studied patients. the study was approved by the ethics committee of shahid beheshti university of medical sciences. researchers adhered to the principles of helsinki declaration and keeping patients’ data confidential. 2.2. participants patients who had been hospitalized with the final diagnosis of mi in the mentioned period were evaluated without any age or sex limitations. inclusion criteria consisted of time interval of less than 24 hours between chest pain and presenting to ed, confirmation of mi based on clinical findings and raise in cardiac enzymes (cpkmb or troponin) in the initial 48 hours of admission. patients with a history of coronary artery bypass grafting (cabg), history of heart blocks including left bundle branch block (lbbb) and right bundle branch block (rbbb), and those with a pace maker as well as cases where the information was not completely available were excluded from the study. 2.3. data gathering data gathering was done using a pre-designed checklist by referring to patients’ medical profile. a senior cardiology resident was in charge of gathering patients’ data. studied variables included demographic data (age and sex), vital signs of the patient on admission to ed, medical history, drug history, left ventricle ejection fraction based on echocardiography findings, ecg findings regarding changes of st segment in lead avr, angiography findings regarding number and location of coronary artery involvement and finally, mortality of the patients. locating the infarct zone was done based on ecg findings and echocardiography confirmation. 2.4. statistical analysis the sample size required for performing the study was estimated as 288 cases by considering the probability of changes being present in lead avr to be 25%, type 1 error of 5%, 80% power, and d = 10%. spss21 software was used for statistical analysis. to report variables, descriptive statistics such as mean ± standard deviation or frequency and percentage were used in tables and a chart. to compare qualitative variables chi square or fisher’s exact tests and for quantitative cases, t-test was applied. additionally, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratio as well as area under the receiver operating characteristic (roc) curve of st elevation ≥ 1 in lead avr were calculated and reported with 95% confidence interval using med calc software. p < 0.05 was considered as significance level. 3. results 3.1. baseline characteristics 288 patients with the mean age of 59.00 ± 13.14 (18 – 91) were evaluated (79.2% male). mean duration of hospitalization was 6.11 ± 4.82 (1 – 45) days. 247 (85.8%) of the mi cases were st elevation mi (stmi) and 41 (14.2%) cases had non stmi. table and figure 1 show the baseline characteristics of the studied patients. more than half of the patients were over 60 years old (50.3%). only, 11 (3.8%) patients had unstable hemodynamics on presentation to ed and all but 10 (3.5%) patients had degrees of decrease in cardiac ejection fraction on admission to ed. based on the results of angiography, 93 (32.3%) cases had three vessel involvement, 85 (29.5%) had two vessel, 63 (21.9%) had single vessel involvement and in 4 cases angiography was normal. table 2 depicts the location of vascular lesion based on angiography results. 168 (58.3%) patients had changes of st segment in lead avr (79.2% male). findings regarding changes in st segment elthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1); e73 table 1: baseline characteristics of the studied patients variable n (%) sex male 228 (79.2) female 60 (20.8) age (year) 15 30 6 (2.1) 30 45 26 (9.0) 45 60 111 (38.5) ≥ 60 145 (50.3) hemodynamic stable 275 (95.5) unstable 11 (3.8) medical history smoking 129 (44.8) diabetes mellitus 78 (27.1) hypertension 119 (41.3) hyperlipidemia 85 (29.5) prior mi 23 (0.8) prior cva 21 (7.3) drug history calcium channel blockers 10 (3.5) β blockers 252 (78.5) nitrates 158 (54.9) aspirin 253 (87.8) clopidogrel 230 (79.9) statins 255 (88.5) acei/arb 240 (83.3) lvef (%) ≥ 55 10 (3.5) 45 – 55 138 (47.9) 35 – 45 78 (25.7) < 35 38 (13.2) mi: myocardial infarction; cva: cardiovascular accident; lvef: left ventricular ejection fraction; acei/arb: angiotensin -converting enzyme inhibitor/angiotensin-receptor blocker. evation in lead avr are summarized in table 3. there was no relationship between presence of these changes with age (p = 0.260), sex (p = 0.977) and type of mi (p = 0.247). 3.2. relationship of st segment changes with outcome there was no significant relationship between presence of st changes in lead avr with infarct location (p = 0.976), number of vessels involved (p = 0.269) and cardiac ejection fraction on admission (p = 0.801). out of the 32 (11.1%) patients who finally died, 25 (78.1%) had st changes in lead avr (odds = 2.72, 95% ci: 1.13 – 6.52, p < 0.020). 3.3. relationship of st elevation ≥ 1 mv with outcome there was no relationship between presence of st elevation ≥ 1 mv in lead avr with infarct location (p = 0.466), number of vessels involved (p = 0.206) and cardiac ejection fraction table 2: location of vascular lesion based on angiographic findings arteries n (%) left main 1 (0.3) left anterior descending proximal 41 (14.2) medial 80 (27.8) distal 5 (1.7) left circumflex proximal 4 (1.4) medial 11 (3.8) distal 2 (0.7) right coronary proximal 30 (10.4) medial 33 (11.5) distal 10 (3.5) others 25 (8.7) table 3: st segment changes in lead avr of the studied patients st changes n (%) normal isoelectric 116 (40.3) elevation 0.5 1 79 (27.4) ≥ 1 24 (8.3) depression 0.5 1 53 (18.4) ≥ 1 12 (4.1) on admission (p = 0.369). however, it had a significant relationship with mortality (odds = 7.72, 95% ci: 3.07 – 19.42, p < 0.001). sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of st elevation ≥ 1 mv in lead avr for prediction of in-hospital mortality were 41.66 (95% ci: 22.79 – 63.05), 91.53 (95% ci: 87.29 – 94.50), 31.25 (95% ci: 16.74 – 50.13), 94.44 (95% ci: 90.65 – 96.81), 0.45 (95% ci: 0.25 – 0.79), and 0.05 (95% ci: 0.03 – 0.09), respectively. in addition, based on area under the roc curve its accuracy was 0.66 (95% ci: 0.53 – 0.76) (figfigure 1: infarct location based on electrocardiographic findings. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. beyranvand et al. 4 figure 2: the area under the roc curve of st segment elevation ≥ 1 millivolt in predicting the mortality of patients with myocardial infarction. ure 2). 3.4. relationship of st depression ≥ 1 mv with outcome there was no significant relationship between st depression ≥ 1 in lead avr with infarct location (p = 0.160), number of vessels involved (p = 0.521), cardiac ejection fraction on admission (p = 0.309) and mortality (p = 0.546). 4. discussion based on the results of the present study, the prevalence of st segment changes in lead avr was estimated to be 58.3%. there was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. however, presence of st elevation ≥ 1 in lead avr was associated with 8 times increase in in-hospital mortality risk. ecg, as a cheap and non-invasive method, has been used for more than 70 years around the world to diagnose cardiac tissue ischemia and mi. among the 12 leads studied in ecg, lead avr can be considered as the most forgotten part of it since no attention is paid to it as the mirror image of other leads. in the last few decades, this lead is regaining its place as an important part of ecg among cardiologists. st segment changes can be considered as the most important ecg finding in diagnosis and evaluation of mis. lead avr is a good reference regarding things that occur in the upper and right side of the heart (15). the findings of this lead are usually covered by the information from the left leads of the heart such as avl, ii, v5, and v6; that is why it has been forgotten. researchers yamaji et al. in 2001 had believed that st segment elevation changes are good indicators of ischemia in the basal parts of the interventricular septum of the heart (16). on the other hand, gorgels et al. in netherlands could link the elevation of st segment in avr with obstruction of the proximal region of the left anterior descending (lad) artery and involvement of the first septal branch of this artery (15). involvement of the distal parts of lad is usually accompanied by st segment depression in avr. wong et al. in 2012 went further and suggested a u shape relationship between 30-day mortality of those with anterior mi and st level in avr (17). so that more than 0.5 mv st segment depression in avr was associated with higher mortality rate during the 30 days after occurrence of anterior mi. the last chest lead (v6) is placed on the axilla midline and a lead v7 in the posterior axillary line can show wide ischemia of the cardiac tip more clearly. this finding is indicative of the importance of the mirror image in avr, which is more reflective of ischemia in the apex of the heart and shows the mirror image of v7 more than any other lead. this means that deeper depression in avr in st is a sign of higher st elevation not only in v5 and v6 leads but also in v7 (17). using st segment, t wave and q wave in lead avr to evaluate the current or past situation of the patients such as previous or current mi has been suggested in various studies (18). although wong believes that st segment changes in lead avr are not significantly related to mortality of mi patients, in 2012 kukla et al. announced that among 320 patients with inferior mi who had st segment changes in various leads of ecg, these changes in lead avr had occurred in half the patients and had a significant relationship with poor prognosis for their problem (10, 17). in the present study, a significant statistical relationship was found between st segment changes in lead avr and mortality of the patients. the higher the elevation, the higher the prevalence of mortality. st segment depression and isoelectric level of the segment, respectively, were associated with lower levels of mortality. some studies have expressed the higher importance of st segment elevation in avr compared with this segment’s depression (12). meanwhile, kukla et al. in their study on 320 individuals observed that patients with inferior wall mi, in case of st elevation in avr had a mortality rate 1.5 times those who had st depression and 30 times those with isoelectric st in avr (10). while, senaratne in 2003 showed that st segment depression in avr was associated with 16 times more patient mortality compared to other cases (11). regarding the anatomy of coronary arteries’ involvement and its relationship with changes in lead avr, no significant relationship was found in our study; however, st segment elevation in avr was accompanied with higher involvement of all 3 coronary arteries. on the other hand, although not statistically significant, proximal obstruction of lad and medial obstruction of the left circumflex artery was accompanied by higher mortality this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1); e73 in patients. mortality rate in the present study was 11.1%, which is higher than the mean mortality rate reported during hospital stay in a meta-analysis done by sorita et al in 2014 (7%) (19). this meta-analysis was carried out on 48 research studies related to the topic and more than 1.5 million patients, and reported mortality of mi patients to be 12% during the 30 days after occurrence of mi. although this study was done on 288 mi patients and the sample size and power of the study were acceptable, its only statistically significant finding was the relationship between st segment elevation in lead avr and in-hospital mortality, which is of course highly important, and st changes in lead avr did not significantly change with lvef changes and coronary artery involvement and its location. it seems that performing prospective cohort studies by considering all of the identified risk factors in prediction of mi patients’ outcome can give a more accurate picture of the role of lead avr findings in prediction of outcome and estimation of location or extent of the necrosis occurring following ischemia. 5. limitation this study was done retrospectively by evaluating patients’ medical profiles and therefore, had the natural limitations associated with these studies such as missing information and not being sure of the accuracy of the reports. other known risk factors of patient outcome were not evaluated in this study, thus, multivariate analysis for identifying independent factors could not be performed. 6. conclusion based on the results of the present study, the prevalence of st segment changes in lead avr was estimated to be 58.3%. there was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. however, presence of st elevation ≥ 1 mv in lead avr was associated with 8 times increase in in-hospital mortality risk. 7. appendix 7.1. acknowledgements we appreciate the cooperation of all the staff of archive unit of medical records in taleghani hospital, tehran, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. reddy ks. cardiovascular disease in non-western countries. n engl j med. 2004;350(24):2438-40. 2. okrainec k, banerjee dk, eisenberg mj. coronary 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senaratne mp, weerasinghe c, smith g, mooney d. clinical utility of st-segment depression in lead avr in acute myocardial infarction. j electrocardiol. 2003;36(1):11-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. beyranvand et al. 6 12. barrabes ja, figueras j, moure c, cortadellas j, solersoler j. prognostic value of lead avr in patients with a first non-st-segment elevation acute myocardial infarction. circulation. 2003;108(7):814-9. 13. mahmoud ks, al rahman tma, taha h, mostafa s. significance of st-segment deviation in lead avr for prediction of culprit artery and infarct size in acute inferior wall st-elevation myocardial infarction. the egyptian heart journal. 2015;67(2):145-9. 14. kosuge m, kimura k, ishikawa t, ebina t, hibi k, toda n, et al. st-segment depression in lead avr: a useful predictor of impaired myocardial reperfusion in patients with inferior 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meta-analysis. bmj. 2014;348:f7393. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2016; 4 (4): 202-206 or i g i n a l re s e a rc h intravenous morphine vs intravenous ketofol for treating renal colic; a randomized controlled trial gholamreza faridaalaee1, neda mohammadi 2∗, seyedeh zahra merghati 3, fatemeh keyghobadi khajeh 4, bahman naghipour 5, mahboob pouraghaei 6, sajjad ahmadi 1 1. emergency medicinedepartment, maragheh university of medical sciences, maragheh, iran. 2. emergency medicinedepartment, urmia university of medical sciences, urmia, iran. 3. international branch of urmia university of medical sciences, urmia, iran. 4. department of community medicine, tabriz university of medical sciences, tabriz, iran. 5. anesthesiologydepartment, tabriz university of medical sciences, tabriz, iran. 6. department of emergency medicine, tabriz university of medical sciences, tabriz, iran. received: 2 december 2015; accepted: 1 january 2016 abstract: introduction: the main purpose of emergency department (ed) managementfor renal colic is prompt pain relief. the present study aimed to compare the analgesic effects of intravenus (iv ) ketofol with morphine in management of ketorolac persistent renal colic. methods: this study is a single blind randomized, clinical trial, on patients who were presented to ed with renal colic, whose pain was resistant to 30 mg iv ketorolac. the patients were randomly assigned to either iv morphine (0.1 mg/kg) or iv ketofol (0.75 mg/kg propofol and 0.75 mg/kg) and the measures of treatment efficacy were compared between the groups after 5 and 10 minutes. results: 90 patients with mean age of 38.01±9.78 years were randomly divided into 2 groups of 45 (66.7% male). treatment failure rate was significantly lower in ketofol group after 5 (20% vs 62.2%, p < 0.001) and 10 minutes (11.1% vs 44.4%, p < 0.001). arr and nnt for ketofol after 5 miutes were 42.22% (95% ci: 23.86 60.59) and 3 (95% ci: 1.7 4.2), respectively. after 10 minutes, these measures reached 33.33 (95% ci:16.16 50.51) and 4 (95% ci: 2.0 6.2), respectively. nnh and ari for hallucination or agitation were 12 (95% ci: 5.8 174.2) and 8.89% (0.57 17.20), respectively. conclusion: the results of the present study, showed the significant superiority of ketofol (nnt at 5 minute = 3 and nnt at 10 minute = 4) in ketorolac resistant renal colic pain management. however, its nnh of 12, could limit its routine application in ed for this purpose. keywords: renal colic; pain; morphine; propofol; ketamine © copyright (2016) shahid beheshti university of medical sciences cite this article as: faridaalaee gh, mohammadi n, merghati sz, keyghobadi khajeh f, naghipour b, pouraghaei m, ahmadi s. intravenous morphine vs intravenous ketofol for treating renal colic; a randomized controlled trial. emergency. 2016; 4 (4): 202-206. 1. introduction r enal colic usually presents as a severe and intermittent flank pain that can radiate to the genitalia, abdomen and groin (1, 2). it is a common cause for emergency department (ed) visits and affects 3-5% of the general population (3). its incidence is higher in men and increases with age (4). the main purpose of ed managament is prompt pain ∗corresponding author: neda mohammadi; department of emergency medicine, imam khomeini hospital, ershad avenue, urmia, iran; tel: +989122347140, fax: +984433457286; email: neda.mohammadi@gmail.com. relief. both non-steroidal anti-inflammatory drugs (nsaids) and opioids are usually used in this regard (1). in a metanalysis, nsaids were found to be as effective as analgesic agents in treatment of acute renal colic (5). nsaids are cheap and easily available but may cause complications such as renal failure and gastrointestinal bleeding (6). opioids are highly potent drugs as well, but havethe risk of dependency and respiratory depression and cause more adverse side effects compared to nsaids (7). in addition, the painwon’t be relieved inup to 42% of renal colic patients treated with morphineand 33% of those treated with ketorolac (8). alternative choices such as ketofol (a combination of ketamine and propofol) are available for this population (9). ketamine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com neda.mohammadi@gmail.com 203 emergency. 2016; 4 (4): 203-206 is a phencyclidine derivative drug with analgesic, amnestic and sedative effects without respiratory side effects (10, 11). in addition, ketamine has antidepressive and smooth muscle relaxant effects that can facilitate stone passage (12). propofol is an alkylphenol derivative drug withsedative effect (13). in ketofol, ketamine and propofol have a synergistic effect with fewer side effects compared to both ketamine and propofol alone (9). based on the above-mentioned points, the present study was aimed to compare the analgesic effects of ketofol withmorphine sulphate in management of ketorolac resistant renal colics. 2. methods 2.1. study setting and design this study is a randomized, controlled, single blind, parallel, clinical trial, which was performed in the ed of imam khomeini hospital, urmia, iran between 23 july 2014 and 18 march 2015. the ethics committee of urmia university of medical sciences approved the study on 20 may 2014 (approval number is umsu. rec. 1393.66). written informed consent was obtained from all participants. the study was registered at iranian registry of clinical trial (irct number: irct2014052417812n1). 2.2. participants this study was conducted on patients whowere presented to ed with chief complaint of flank pain and highly suspectedrenal colic. all patients, whose pain severity was greater than 7 and did not respond to 30 mg intravenous (iv ) ketorolac, were includedusing convenience sampling. the exclusion criteria were possible allergy to nsaids, opioids, propofol, egg, and ketamine; addiction to opioid; renal failure; gastrointestinal bleeding and recent use of analgesics. renal colic was defined as acute severe flank pain that radiated to ipsilateral groin. the intensity of pain was measured on a 100 millimeter (10 numerical) visual analogue scale (vas). 10 was considered the worst possible pain and 0 was considered painless. 2.3. intervention patients were randomly divided into two groups using permutated blocks of 4. each block contained a pre-specified number of treatment assignments in a random order. allocation was planned before starting the study by one of the authors. participants and data analysts were blinded to treatment allocation. we could not blind the researcher as a result of rapid sedative effects of ketofol. all renal colic patients received 30 mg iv ketorolac, and pain intensity was measured before and 10 minutes after injection. if patients pain score had not decreased by at least 3 scores after 10minutes, the second step was begun and the patient was enrolled in the study. in group 1, (control group) patients were given 0.1 mg/kg iv morphine sulfate and in group 2 (intervention group) patients were given iv ketofol (combination of 0.75 mg/kg propofol and 0.75 mg/kg ketamine) (14). the ketorolac, morphine, ketamine, and propofol (provive) used, were made by alborz darou company of iran, darou pakhsh company of iran, hameln company of germany and claris company of india, respectively. 2.4. outcome based on previous studies, 13mm reduction on vas is clinically significant; but in patients with severe pain, a greater change on vas is considered pain reduction (15-17). thus,a treatment leading to at least 3 scores reduction in pain intensity was considered effective. if pain score had not dropped by at least 30 mm after 10 minutes, pain management was considered unsuccessful. the patients were under continuousmonitoring of blood pressure, o2 saturation, and respiratory and heart rates. respiratory depression, hallucination, agitation, nausea, vomiting, and emergence phenomenon were considered as secondary outcomes (complication). 2.5. statistical analaysis considering 80% power, 95% confidence interval (ci), 1.7 variance of pain severity, and 0.8 minimum significant difference, sample size of 45 patients in each group was calculated to be enough. data were analyzed using spss 19. quantitative variables difference were assessed by mann whitney u test, and qualitative and numerical variables difference were assessed by chi-square and fishers exact tests. number needed to treat (nnt), relative risk reduction (rrr), and absulute risk reduction (arr), as well asnumber needed to harm (nnh) and absulute risk increase (ari)were used as measures of treatment efficacy. p< 0.05 was considered statistically significant. 3. results 90 patients with mean age of 38.01 ± 9.78 years (22-78) were randomly divided into 2 groups of 45(66.7% male). table 1 summarizes demographic data of the participants. initial pain score was 9.0 ± 1.2 in morphine and 9.2 ± 1.1 in ketofol groups (p = 0.469). table 2 compares the characteristics of pain management and complications betweenthe 2 groups.treatment failure rate was significantly lower in ketofol group after 5 (20% vs 62.2%, p <0.001) and 10 minutes (11.1% vs 44.4%, p < 0.001). arr and nnt for ketofol after 5 miutes were 42.22% (95% ci: 23.86 60.59) and 3 (95% ci: 1.7 4.2), respectively. after 10 minutes, these measures reached 33.33 (95% ci:16.16 50.51) and 4 (95% ci: 2.0 6.2), respectively. nnh and ari for hallucination or agitation were 12 (95% ci: 5.8 174.2) and 8.89% (0.57 17.20), respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com gh. faridaalaee et al. 204 table 1: demoghraphic characteristics of the studied patients variables morphine sulfate ketofol p-value sex; n (%) male 31 (68.9) 29 (64.4) 0.823 female 14 (31.1) 16 (35.6) age mean ± sd (year) 39.29 ± 12.40 36.73 ± 6.05 0.217 weight mean ± sd (kg) 70.73 ± 13.28 75.82 ± 10.83 0.049 stone size mean ± sd (mm) 6.38 ± 1.85 6.04 ± 1.76 0.383 sd: standard deviation. table 2: comparision of treatment effects and cmplications between morphine and ketofol groups variables morphine sulfate ketofol p-value pain intensity mean± sd on admission 9.00 ± 1.22 9.18 ± 1.09 0.469 5 minutes after administration 6.76 ± 3.13 3.24 ± 2.83 < 0.001 10 minutes after administration 4.96 ± 3.83 2.40 ± 2.77 <0.001 failure rate; n (%) 5 minutes after administration 28 (62.2) 9 (20) < 0.001 10 minutes after administration 20 (44.4) 5 (11.1) < 0.001 complication; n (%) hallucination, agitation 0 (0) 4 (8.9) < 0.058 nausea, vomiting 2 (4.4) 0 (0) < 0.041 stone size mean ± sd (mm) 6.38 ± 1.85 6.04 ± 1.76 0.383 sd: standard deviation. 4. discussion the results of the present study, showed the significant superiority of ketofol (nnt at 5 minute = 3 and nnt at 10 minute = 4) in rapid pain management of patients presented to ed complaining from renal colic and resistant to ketorolac. nnt of 3 means that about one in every 3 patients treated with ketofol will benefit from the treatment after 5 minutes. however, its nnh was 12, which means that about one in every 12 patientstreated with ketofol will be affected with hallucination andagitation. this relatively high nnh could limit routine application of ketofol in this regard. we didn’t find any studiesthatverified using ketofol for treating acute pain of urolithiasisup to the time of writing this article. thus, this study is the first to verify the effect of ketofol, and compare iv ketofol with iv morphine for treating acute renal colic. regarding the opioid agents for treating acute renal colic, the result of our study is similar to those previously published (1, 18-23). holdgate and pollock, performed a systematic review on efficacy of nsaids and opioids. they reported that patients who received opioids, neededa rescue dose of analgesicsmore frequently (1). safdar et al. investigated the effect of ketorolac and morphine for treating renal colic. they reportedthat 30% of the patients who received a combination of ketorolac and morphine needed a rescue dose (8). masoumi et al. compared iv acetaminophen with morphine for treating renal colic and concluded that acetaminophen is more effective than morphine (24). in contrast, azizkhani et al. reported that morphine is more effective than acetaminophen for this purpose (25). however, both groups reported that morphine had more side effects (24, 25). in addition, soleimanpour et al. compared iv lidocaine and morphie, and showed that lidocaine is siginificantly more effective in relieving pain in renal colic patients (26). yet, bektas et al. revealed that paracetamol and morphine are equally effective for this purpose (27). researchers have been trying to verify an alternative drug for treating acute renal colic in emergency settings (28). ketofol has been used in anesthesiology and has recently begun to spread into ed (29). nejati et al. compared ketamine/propofol and midazolam/fentanyl in the ed and found that ketamine/propofol is safe and effective for sedation and analgesia (14). willman et al. evaluated the effectiveness of ketofol for orthopedic procedural sedation in ed. they concluded that ketofol is an effective drug with minimal and transient side effects (9). the present study illustrated that efficacy of ketofol in renal colic pain relief is more than morphine. however, further study is needed before we suggestroutine use of ketofol, in this regard. 4.1. limitations due to sedative effect of ketofol, we could only blind the patients and not the researchers, thus this study issingle blind. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 205 emergency. 2016; 4 (4): 205-206 conveniences amplingand short duration of follow-up are also among the most important limitations of the present trial. 5. conclusion the results of the present study, showed the significant superiority of ketofol (nnt at 5 minute = 3 and nnt at 10 minute = 4) in ketorolac resistant renal colic pain management. however, it’s nnh of 12, could limit its routine application in ed for this purpose. 6. appendix 6.1. acknowlegdment all authors would like to thank all the staff of imam khomeini hospital of urmia and the research center of urmia university of medical sciences. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interests none 6.4. funding none references 1. holdgate a, pollock t. systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. bmj. 2004; 328 (7453): 1401. 2. green br. renal calculi: emergency department diagnosis and treatment. emerg med pract. 2011; 13 (7):1-17. 3. hiatt ra, dales lg, friedman gd, hunkeler em. frequency of urolithiasis in a prepaid medical care program. am j epidemiol. 1982; 115 (2): 255-65. 4. soucie jm, thun mj, coates rj, mcclellan w, austin h. demographic and geographic variability of kidney stones in the united states. kidney int. 1994; 46 (3):893-9. 5. labrecque m, dostaler l, rousselle r, nguyen t, poirier s. efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic: a meta-analysis. arch intern med. 1994; 154 (12): 1381-7. 6. tramr’r dm, williams j, carroll d, wiffen p, moore r, mcquay h. comparing analgesic efficacy of nonsteroidal antiinflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. acta anaesthesiol scand. 1998; 42 (1): 71-9. 7. ricardo buenaventura m, rajive adlaka m, nalini sehgal m. opioid complications and side effects. pain physician. 2008; 11: s105s20. 8. safdar b, degutis lc, landry k, vedere sr, moscovitz hc, d’onofrio g. intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. ann emerg med. 2006; 48 (2): 173-81. 9. willman ev, andolfatto g. a prospective evaluation of ”ketofol” (ketamine/ propofol combination) for procedural sedation and analgesia in the emergency department. ann emerg med. 2007; 49 (1): 23-30. 10. white pf, way wl, trevor aj. ketamineits pharmacology and therapeutic uses. anesthesiology. 1982 (56): 11936. 11. green sm, rothrock sg, lynch el, et al. intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. ann emerg med. 1998;31 (6): 688-97. 12. katalinic n, lai r, somogyi a, mitchell pb, glue p, loo ck. ketamine as a new treatment for depression: a review of its efficacy and adverse effects. aust n z j psychiatry. 2013; 47 (8): 710-27. 13. shafer a, doze v, shafer s, white p. pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia. anesthesiology. 1988; 69 (3): 348-56. 14. nejati a, moharari rs, ashraf h, labaf a, golshani k. ketamine/propofol versus midazolam/ fentanyl for procedural sedation and analgesia in the emergency department: a randomized, prospective, double-blind trial. acad emerg med. 2011; 18 (8): 800-6. 15. bird sb, dickson ew. clinically significant changes in pain along the visual analog scale. ann emerg med. 2001; 38 (6): 639-43. 16. gallagher ej, liebman m, bijur pe. prospective validation of clinically important changes in pain severity measured on a visual analog scale. ann emerg med. 2001; 38 (6): 633-8. 17. todd kh. clinical versus statistical significance in the assessment of pain relief. ann emerg med. 1996; 27 (4): 439-41. 18. cordell wh, wright sw, wolfson ab, et al. comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. ann emerg med. 1996; 28 (2): 151-8. 19. larkin gl, peacock wf, pearl sm, blair ga, d’amico f. efficacy of ketorolac tromethamine versus meperidine in the ed treatment of acute renal colic. am j emerg med. 1999; 17 (1): 6-10. 20. oosterlinck w, philp n, charig c, gillies g, hetherington j, lloyd j. a double-blind single dose comparison of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com gh. faridaalaee et al. 206 intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic. j clin pharmacol. 1990; 30 (4): 336-41. 21. persson nh, bergqvist d, melander a, zederfelt b. comparison of a narcotic (oxicone) and a non-narcotic antiinflammatory analgesic (indoprofen) in the treatment of renal colic. acta chir scand. 1985; 151 (2): 105-8. 22. sandhu d, iacovou j, 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effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. bmc urol. 2012; 12(1): 1-5. 27. bektas f, eken c, karadeniz o, goksu e, cubuk m, cete y. intravenous paracetamol or morphine for the treatment of renal colic: a randomized, placebo controlled trial. ann emerg med. 2009; 54 (4): 568-74. 28. esmailian m, keshavarz m. synergistic effects of citalopram and morphine in the renal colic pain relief; a randomized clinical trial. emergency. 2014; 2 (1): 26-9. 29. arora s. combining ketamine and propofol (ketofol) for emergency department procedural sedation and analgesia: a review. west j emerg med. 2008; 9 (1): 20-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (1): 30-35 30 original research cause of emergency department mortality; a case-control study hossein alimohammadi1, farahnaz bidarizerehpoosh2, farzaneh mirmohammadi1*, ali shahrami1, kamran heidari3, anita sabzghabaie3, shahram keikha4 1. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of pathology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran 4. department of emergency medicine, mashhad university of medical sciences, mashhad, iran abstract introduction: based on previous studies, cardiovascular diseases, traffic accidents, traumas and cancers are the most important etiology of mortalities in emergency departments (ed). however, contradictory findings have been reported in relation to mortality in emergency departments. therefore, the present study was undertaken to evaluate the role of clinical factors in mortality among patients referring to an emergency department in a third level hospital in tehran, iran. methods: in the present case-control study, all the patients over 18 years of age were evaluated, referring to the ed of imam hossein hospital, tehran, iran, from the beginning of 2009 to the end of 2010. the patients died in the ed were placed in the case group and those discharged or hospitalized in other hospital wards in the control group. demographic data, background diseases, and the final diagnoses were recorded. chi-squared test, multivariate logistic regression, and pearson’s correlation coefficient were used to evaluate the relationship between the variables mentioned above and patient mortality. results: 2907 patients (969 (59.9% male) in the case and 1938 (62.2% male) in the control groups) were evaluated. cardiovascular diseases (39.2%), severe traumas (18.5%), and cerebrovascular accidents (17.7%) were the most frequent etiology of patient mortality in ed. multivariate regression analysis showed that presentation with cardiovascular complaints (or=7.3; 95% ci: 3.5-16.1; p<0.001), a history of hypertension (or=5.4; 95% ci: 1.2-12.3; p<0.001), severe trauma (or=4.6; 95% ci: 2.0-13.2; p<0.001), age over 60 (or=3.8; 95% ci: 1.8-7.8; p<0.01) and a final diagnosis of renal disease (or=3.4; 95% ci: 2.1-6.4; p<0.001) were factors that increased the odds of mortality in patients referring to the ed. multivariate regression analysis in patients over 60 years showed that sepsis was an independent factor increasing the risk of death (or=2.9; 95% ci: 1.3-5.9; p=0.009). a patient’s risk of death increases with an increase in the number of risk factors in that patient (r2=0.96; p=0.02). conclusion: it appears the odds of mortality in patients referring to ed with cardiovascular complaints, a history of hypertensive, severe trauma, age over 60 and a final diagnosis of renal disease are higher versus other patients. in addition, the patients’ odds of death increase with an increase in the number of risk factors. such an increase is more noticeable at age over 60. key words: emergency department; etiology; mortality; risk factor cite this article as: alimohammadi h, bidarizerehpoosh f, mirmohammadi f, et al. cause of emergency department mortality: a case-control study. emergency. 2014;2 (1): 30-5. introduction:1 atient mortality in emergency departments (ed) is a problem which has aggravated in recent years; in this context the mortality rate has increased 26% from 1998 to 2000 in the united states (1, 2). previous studies have shown that cardiovascular conditions, traffic accidents, traumas and cancers are the most important etiology of mortalities in ed (3). however, the etiology differs in various geographical locations (4). for example, it has been reported that 1560% of all the mortalities in hospitals occur in ed (5, 6). such discrepancies in reports might be attributed to the type of referred patients, crowdedness, and whether the department is an educational center or not (7-9). in *corresponding author: farzaneh mirmohammadi: imam hossein hospital, shahid madani ave, tehran, iran. telefax: +989125597918. email: f.mirmohammadi1@gmail.com received: 19 december 2013; accepted: 11 february 2014 recent years, several attempts have been made to identify factors responsible for patient mortality (9-13). however, the results have been contradictory in most cases, i.e. some reports suggested a phenomenon or a medical condition as a risk factor while others rejected such claims. therefore, more studies are needed to make a true judgment about the patient mortality in ed. the present study was carried out to evaluate the role of clinical factors and variables in the mortality of patients referring to the ed of a third-level hospital through 2009-2010. methods: study design and setting in the present case-control study patients, over 18 years of age were enrolled, referred to the ed of imam hossein hospital (about 6000 admission/month) in tehran, iran, from the beginning of 2009 to the end of 2010. the protocol of the study was approved by the p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 31 alimohammadi et al ethics committee of shahid beheshti university of medical sciences. during the study period, researchers have observed the principles of helsinki declaration. before beginning the study the patients, their family members, or acquaintances signed an informed consent form. data were collected from patient files. for those cases who had file deficiencies, data were completed and collected during follow-ups. subjects patients died in the ed through 2009-2010 were included in the case group. the subjects in the control group consisted of patients discharged from ed or hospitalized in other wards of the hospital. the patients were followed up in a week after being discharged. exclusion criteria consisted of having no interest in taking part of the study, outpatient admission, lack of possibility to follow the patient due to dropout from the study based on personal request (the control group) or transfer to other centers, and succumbing to death before being admitted into the ed. it should be pointed out that those who died in the control group during 48 hours after decision-making process were excluded from the study. the subjects were selected using a simple sampling technique. to this purpose, at the end of each day all the patients died in the ed were listed based on files’ number of which two files were randomly selected and evaluated. for each case, two control patients were randomly selected from the discharged or hospitalized patients of the same day. the number of subjects in each group was estimated at 117 subjects at α=0.05 and β=0.1 considering the odds ratio of 3.2 for death in patients with cardiovascular conditions based on previous studies (14). data collection data were collated and recorded by a trained emergency physician. totally, 969 deceased patients during a two-year period were evaluated in the case group and 1938 ones in the control. demographic data (age, gender and educational status), underlying diseases (diabetes, cardiovascular conditions, hypertension, cancer, aids, renal, and hepatic diseases), and the final diagnoses were recorded. the diagnoses were categorized into the eight groups of cardiac conditions (ischemic cardiac diseases, acute myocardial infarction, coronary atherosclerotic diseases, and cardiac insufficiency), renal diseases (acute renal insufficiency, nephritis, etc.), trauma, cancer, sepsis, pneumonia, cerebrovascular accident and others. trauma was divided into two groups including minor and major traumas. minor traumas consisted of muscle and tendon strains, sprains, and joint injuries; major traumas contained spinal cord injuries, intracranial injuries, penetrating abdominal injuries, blunt hemorrhagic abdominal injuries, and major chest injuries. other conditions consisted of all the other diagnoses, including syncope, infection, psychological disorders, nervous system disorders, musculoskeletal disorders, skin and connective tissue disorders, and mild traumas. statistical analyses data were analyzed with stata 11.0 statistical software. chi-squared test and independent t-test were used to compare qualitative and quantitative variables, respectively. subsequently, multivariate logistic regression was performed to determine independent risk factors of mortality. the results were reported as odds ratios (or) at a 95% confidence interval. in addition, pearson’s correlation coefficient was used to evaluate number of ed referred 154250 outpatient cases: 92550 number of death: 2090 number of ed admission: 59610 number of controls: 1938 number of cases: 969 excluded: exclusion criteria: 6250 randomization: 51422 excluded: exclusion criteria: 150 randomization: 971 figure 1: flowchart of patient selection.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 32 emergency (2014); 2 (1): 30-35 the correlation between the number of risk factors in one patient and odds of death. statistical significance was defined as p<0.05. results: finally, 2907 patients (969 cases and 1938 controls) were evaluated (figure 1). the means and standard deviations of patient ages in the case and control groups were 67.4±9.6 and 46.8±11.7 years, respectively (p< 0.0001). there were 575 (59.3%) females and 1206 (62.2%) males in the case and control groups, respectively (p=0.13). in the case group, 562 (58%) patients had a history of hypertension, 251 (25.9%) cardiac diseases, 95 (9.8%) cancer, and 94 (9.7%) renal diseases. chi-squared test showed a significant relationship betable 1: the separate subjects’ demographic data for the case and control groups  variable case control p age (mean ± sd) male 69.9±10.2 48.2±12.5 <0.0001 female 64.7 ±6.8 45.1±11.0 total 67.4±9.6 46.8±11.7 gender male 575 (59.3) 1206 (62.2) 0.13 female 394 (40.7) 732 (37.8) marital status single 79 (87.2) 126 (6.5) 0.1 married 890 (91.8) 1812 (93.5) educational status < high school 509 (52.5) 1066 (55.0) 0.2 ≤ high school 460 (47.5) 870 (45.0) underlying diseases aids 1 (0.1) 3 (0.15) 0.74 hepatic disease 63 (6.5) 192 (9.9) 0.002 renal disease 105 (10.8) 238 (12.3) 0.25 cancer 22 (2.3) 47 (2.4) 0.8 cardiac disease 251 (25.9) 194 (10.0) <0.0001 hypertension 562 (58) 341 (17.6) <0.0001 diabetes 166 (17.1) 270 (13.9) 0.02 table 2: the subjects’ final diagnosis stratifying for the case and control groups  disease case control p cardiac disease 380 (39.2) 215 (11.1) <0.0001 severe trauma 179 (18.5) 165 (8.5) <0.0001 cva 172 (17.7) 285 (14.7) 0.03 sepsis 127 (13.1) 296 (15.3) 0.12 renal disease 36 (3.7) 12 (0.6) <0.0001 pneumonia 30 (3.1) 44 (2.3) 0.2 cancer 22 (2.3) 47 (2.4) 0.8 *others 23 (2.4) 874 (45.1) <0.0001 *includes syncope, infections, psychological conditions, nervous system disorders, musculoskeletal diseases, skin and connective tissue conditions, and mild trauma. cva: cerebrovascular accident. table 3: odds ratio (or) at a confidence interval of 95% for factors affecting patient mortality  factor or (ci: 95%) p presentation with cardiac complaint 7.3 (3.5-16.1) <0.001 a history of hypertension 5.4 (1.2-12.3) <0.001 presentation with severe trauma 4.6 (2.0-13.2) <0.001 age>60 3.8 (1.8-7.8) 0.01 a final diagnosis of renal disease 3.4 (2.1-6.4) <0.001 other disease* 0.2 (0.06-0.9) <0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 33 alimohammadi et al tween underlying diseases and mortality (table 1). the most frequent final diagnoses in the case group consisted of cardiopulmonary diseases (39.2%), severe traumas (18.5%), cerebrovascular accident (17.7%), sepsis (13.1 %), renal diseases (3.7%), pneumonia (3.1%), and cancer (2.3%) in descending order (table 2). logistic regression showed that age over 60 (or=3.8; 95% ci: 1.8-7.8; p=0.01), a history of hypertension (or=5.4; 95% ci: 1.2-12.3; p<0.001), presentation with cardiac complaints (or=7.3; 95% ci: 3.5-16.1; p<0.001), severe trauma (or=4.6; 95% ci: 2.0-13.2; p<0.001), and renal diseases (or=3.4; ci: 2.1-6.4; p<0.001) were independent factors that increased the odds of death in patients admitted into the ed. however, the odds of death were lower in patients with other diseases (or=0.2; 95% ci: 0.06-0.9; p<0.001) (table 3). multivariate regression analysis of patients over 60 years showed that sepsis, as an independent factor, increased the odds of mortality in such patients (or=2.9; 95% ci:1.3-5.9; p<0.009). evaluation of the relationship between the presence of several risk factors in one patient and the death risk showed that the odds of death increased in an individual with the presence of several risk factors (r2=0.96; p=0.02) (figure 2). discussion: the results of the present study showed that the odds of death in patients referring to ed with cardiac complaints, a history of hypertension, severe trauma, age over 60 and renal conditions, are higher than those in patients with other diseases. in addition, there is an increase in the odds of death with an increase in the number of risk factors. such an increased risk is more prominent in patients over 60. although the incidence of mortalities due to heart diseases has significantly decreased in recent years (from 64% to 49%), they still have the highest incidence rate (15, 16). the present study showed that cardiac complaints are the most important etiology of early death in patients referred to ed. since studies have shown that the majority of deaths due to myocardial infarction take place during the first few hours after the appearance of symptoms and signs, the most important physiologic risk in cardiac patients is a delay in instituting therapeutic care. thus, early management of such patients, especially for those who have myocardial infarction, might save their lives and decrease mortality rate. (17). hypertension is an important and independent risk factor for patient mortality. the analyses carried out in the present study showed that the concomitant affliction with hypertension and cardiac disease increases the patient’s odds of death up to 10 times (or=10.3; ci: 5.6-18.8; p<0.001). (18, 19). in addition, hypertension leads to cardiovascular disease; therefore, hypertension has direct effects on the mortality of patients referring to ed. it was estimated in 2004 that approximately 1 billion adults all over the world (333 million people in developed countries and 639 people in developing countries) have hypertension, 4 million of whom die due to the direct effects of hypertension (20, 21). based on world health organization (who), it was estimated that high blood pressure accounts for 1 in 8 deaths and is the third killer all over the world (22). therefore, evaluation of hypertension is of utmost importance in ed; however, in most cases, it ignored or did not pay adequate attention. in the present study, a final diagnosis of renal disease was one of the factors increasing the odds of death in patients referring to the ed. consistent with the results of previous studies it indicates a graded association between decreases in glomerular filtration rate and the risk of mortality, developing cardiovascular disease and hospitalization (23, 24). while some studies have not shown an independent effect of renal disease on increasing the risk of mortality others have reported that cardiovascular effects of renal diseases result in death (25-27). this discrepancy is attributed to the fact that renal disease can lead to cardiovascular disease (26, 28) and cardiovascular disease, in itself, can result in renal diseases (25, 28). as a result, it is not easy to make a distinction between the outcomes of these two diseases. that’s why patients with renal disease, who have cardiovascular diseases too, have more severe outcomes, including a decrease in life expectancy and an increase in the risk of mortality (29-31). in the present study, sepsis was a significant factor affecting the odds of death in patients over 60, consistent with the results of other studies in this age group (12). when the frequency of septic cases was evaluated in different age groups, it was shown that of 182 patients with sepsis in the case group, 86.3% were over 60 years; however, only 52.2% of patients in the control group were over 60. limitation the study sample cannot completely reflect the situa figure 2: association of number of risk factors and odds of death stratified by age.  8.1 10.3 13.2 19.3 3.7 5.1 6.4 8.1 0 5 10 15 20 1 2 3 4 o d d r a ti o f o r d e a th number of risk factors age=<60 age>60 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 34 emergency (2014); 2 (1): 30-35 tion of iranian population and include all the ethnicities in iran. however, based on some studies, data collected in a capital city may reflect an acceptable pattern of the whole country (32). because the aim of the study was to evaluate the effect of clinical factors on the mortality, only clinical variables were evaluated. therefore, it is advisable to design future studies for the evaluation of environmental, geographical and social aspects so that the effects of such factors can be analyzed, too. however, the present study was the only case-control study in the mediterranean region to evaluate the important mortality risk factors in ed. having a large sample size was one of the advantages of the study. conclusion: it appears the odds of mortality in patients referring to ed with cardiovascular complaints, a history of hypertensive, severe trauma, age over 60 and a final diagnosis of renal disease are higher compare to other patients. in addition, the patients’ odds of death increase with an increase in the number of risk factors. such an increase is more noticeable at age over 60. acknowledgments: we acknowledge all staffs of imam hossein hospital, tehran, iran. conflict of interest: none funding support: none authors’ contributions: hossein alimohammadi, farzaneh mirmohammadi, and kamran heidari have designed the study. farzaneh mirmohammadi, farahnaz bidarizerehpoosh, and shahram keikha collected the data. ali shahrami analyzed the data. anita sabzghabaie wrote the first draft. all authors read and approved the final version of the manuscript. references: 1. ly n, mccaig lf. national hospital ambulatory medical care survey: 2000 outpatient department summary. adv data. 2002 (327):1-7. 2. olsen jc, buenefe ml, falco wd. death in the emergency department. ann emerg med. 1998;31(6):758-65. 3. zheng zj, croft jb, giles wh, mensah ga. sudden cardiac death in the united states, 1989 to 1998. circulation. 2001; 104(18):2158-63. 4. wall m, huang j, oswald j, mccullen d. factors associated with reporting multiple causes of death. bmc med res methodol. 2005;5(1):4-17. 5. jarman b, gault s, alves b, et al. explaining differences in english hospital death rates using routinely collected data. bmj. 1999;318(7197):1515-20. 6. nelson p. death in the emergency department :the forgotten tragedy. j pain symptom manage. 2011;41(1):2159. 7. halm ea, chassin mr. why do hospital death rates vary? n engl j med. 2001;345(9):692-4. 8. hoot nr, aronsky d. systematic review of emergency department crowding: causes, effects, and solutions. ann emerg med. 2008;52(2):126-36. 9. shapiro ni, wolfe re, moore rb, smith e, burdick e, bates dw. mortality in emergency department sepsis (meds) score: a prospectively derived and validated clinical prediction rule. crit care med. 2003;31(3):670-5. 10. baker m, clancy m. can mortality rates for patients who die within the emergency department, within 30 days of discharge from the emergency department, or within 30 days of admission from the emergency department be easily measured? emerg med j. 2006;23(8):601-3. 11. cameron pa, richardson db. increase in patient mortality at 10 days associated with emergency department overcrowding. med j aust. 2006;184(5):213-6. 12. caterino jm, kulchycki lk, fischer cm, wolfe re, shapiro ni. risk factors for death in elderly emergency department patients with suspected infection. j am geriatr soc. 2009;57 (7):1184-90. 13. salazar a, bardés i, juan a, olona n, sabido m, corbella x. high mortality rates from medical problems of frequent emergency department users at a university hospital tertiary care centre. eur j emerg med. 2005;12(1):2-5. 14. van dam rm, li t, spiegelman d, franco oh, hu fb. combined impact of lifestyle factors on mortality: prospective cohort study in us women. bmj. 2008;337:a1440. 15. de vivo mj, stuart krause j, lammertse dp. recent trends in mortality and causes of death among persons with spinal cord injury. arch phys med rehabil. 1999;80(11):1411-9. 16. melanie w, jinzhou h, john o, diane mc. factors associated with reporting multiple causes of death. bmc med res methodol. 2005; 5: 4:4-17. 17. cannon cp, gibson cm, lambrew ct, et al. relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. jama. 2000;283(22):2941-7. 18. frankel fm, duong n, shil ab. association of hypertension with mortality. am j hypertens. 2010;23(5):452-3. 19. gombojav b, yi s-w, sull jw, nam cm, ohrr h. combined effects of cognitive impairment and hypertension on total mortality in elderly people: the kangwha cohort study. gerontology. 2011;57(6):490-6. 20. kearney pm, whelton m, reynolds k, muntner p, whelton pk, he j. global burden of hypertension: analysis of worldwide data. the lancet. 2005;365(9455):217-23. 21. lawes cm, hoorn sv, rodgers a. global burden of bloodpressure-related disease, 2001. the lancet. 2008;371(9623): 1513-8. 22. world health organization. a global brief on hypertension. silent killer, global public health crisis. world health organization. geneva: world health organization; 2013. 23. gabayan gz, derose sf, asch sm, et al. patterns and predictors of short-term death after emergency department discharge. ann emerg med. 2011;58(6):551-8. 24. go as, chertow gm, fan d, mcculloch ce, hsu c. chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. n engl j med. 2004;351(13):1296-305. 25. ma k, greene e, raij l. cardiovascular risk factors in chronic renal failure and hemodialysis populations. am j kidney dis. 1992;19(6):505-11. 26. muntner p, he j, hamm l, loria c, whelton pk. renal insufficiency and subsequent death resulting from cardiovascular disease in the united states. j am soc nephrol. 2002;13(3):745-53. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 35 alimohammadi et al 27. sarnak mj, levey as, schoolwerth ac, et al. kidney disease as a risk factor for development of cardiovascular disease. circulation. 2003;108(17):2154-69. 28. mccullough pa, wolyn r, rocher ll, levin rn, o’neill ww. acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. am j med. 1997; 103(5):368-75. 29. collins aj, foley rn, herzog c, et al. us renal data system 2010 annual data report. am j kidney dis. 2011;57(1):1-9. 30. foley rn, collins aj. end-stage renal disease in the united states: an update from the united states renal data system. j am soc nephrol. 2007;18(10):2644-8. 31. goodman wg, goldin j, kuizon bd, et al. coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. n engl j med. 2000;342(20):1478-83. 32. hosseini m, carpenter r, mohammad k. growth of children in iran. ann hum biol. 1998;25(3):249-61. emergency. 2017; 5 (1): e46 ca s e re p o rt paradoxical embolism due to persistent foramen ovale; a case report dormar david barriosi 1, jonathan roncancio 1, albert alejandro avila1∗, jaime andres alvarado1, ana cristina montenegro1 1. emergency department, fundacion santa fe de bogota hospital, bogota, colombia. received: august 2016; accepted: august 2016; published online: 14 january 2017 abstract: the mean percentage of cryptogenic strokes among ischemic strokes is 31%, of which one-third may be associated with patent foramen ovale. the foramen ovale is required for blood flow through the fetal atrial septum. it is formed as of the fourth week of gestation, and this leads to right-left interatrial shunt that allows the passage of oxygenated blood to systemic circulation. in 75% of cases, its closure is complete by 2 years of age, but it may persist in 25% of patients. we present the case of a patient with paradoxical embolism in the lower extremities and ischemic stroke in the clinical context of a patent foramen ovale. keywords: embolism, paradoxical; blood coagulation; anticoagulants; emergency department; venous thromboembolism © copyright (2017) shahid beheshti university of medical sciences cite this article as: barrios dd, roncancio j, avila aa, alvarado ja, montenegro ac. paradoxical embolism due to persistent foramen ovale; a case report. emergency. 2017; 5 (1): e46. 1. introduction the mean percentage of cryptogenic strokes among ischemic strokes is 31%, of which one-third may be associated with patent foramen ovale (1). the foramen ovale is required for blood flow through the fetal atrial septum. it is formed as of the fourth week of gestation, and this leads to right-left interatrial shunt that allows the passage of oxygenated blood to systemic circulation. in 75% of cases, its closure is complete by 2 years of age, but it may persist in 25% of patients (2). here a rare presentation of embolism was reported as an excuse to discuss a special aspect of paradoxical thromboembolism. 2. case presentation: a 64-year-old female patient was admitted to emergency department due to sudden asthenia, adynamia, vertiginous sensation, and feeling faint. subsequently, she reports retrosternal chest pain that was associated with dyspnea, dysarthria, bradypsychia, and hypoprosexia. therefore, the immediate response team goes into action for stroke code ∗corresponding author: albert alejandro avila; emergency department, fundacion santa fe de bogota hospital, bogota, colombia; tel: +5716196698, email: alejandroavila2010@gmail.com. activation. medical history of importance was that she underwent left knee arthroscopy three days before admission. her vital signs on arrival were as follows: blood pressure, 90/60 mmhg; heart rate 59 beats/minute; respiratory rate, 18 breaths/minute; and axillary temperature, 36.9 ◦c. from a neurological point of view, she was alert, disoriented in time with fluctuating nomination, repetition alteration, phonetic, semantic paraphasias, and hypoesthesia in right side of body. brain magnetic resonance imaging (mri) and magnetic resonance angiography (mra) shows small acute infarctions at the left frontal cortical, probably due to hypoperfusion or micro emboli (figure 1). afterwards, a transesophageal echocardiogram was carried out, which shows a foramen ovale that allows passage of abundant amount of bubbles to the left atrium, associated with severe tricuspid valve insufficiency and high probability of pulmonary hypertension (pulmonary artery systolic pressure of 58 mmhg). due to the findings from the echocardiogram, a ventricular b-type natriuretic peptide (bnp) test was conducted with a result of 132 pg/ml, as well as high sensitivity troponin i assay with a result of 1044 ng/dl (reference value 50 ng/dl). the pretest probability was calculated using the wells’ scale and a high probability was obtained. therefore, a computed tomography (ct) angiography was carried out, and it showed evidence of pulmonary thromboembolism which jeopardizes the segmental and sub-segmental branches of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com alejandroavila2010@gmail.com a. alejandro avila et al. 2 figure 1: brain magnetic resonance imaging (mri) and magnetic resonance angiography (mra) of patient. figure 2: axial and coronal plan cuts of chest angiogram. the upper lobes, lingula, middle lobe, and both lower lobes (figure 2). the risk of paradoxical embolism (rope) score was calculated, and it shows an intermediate probability. the pulmonary embolism severity index (pesi) score was determined to be 154 points that corresponds to a class v risk (very high risk). from the above findings, paradoxical embolism has manifested itself due to vascular ischemic attack and pulmonary embolism of intermediate risk as a result of elevated troponin levels and signs of right ventricular dysfunction, in the context of a patent foramen ovale. full anticoagulation treatment was started with heparins of low molecular weight, enoxaparin, and the patient is considered not to be a suitable candidate for thrombolysis with instructions to be monitored in an intensive care unit (icu). the patient satisfactorily evolved and in view of clinical improvement, the patient is discharged with the factor xa inhibitor (apixaban) without a loading dose. treatment was continued for 6 months, in addition to physical rehabilitation and language therapy. an outpatient control was held a month after the event, and major neurological improvement was evidenced but paraphasia is still present. 3. discussion: although the majority of people with patent foramen ovale are asymptomatic, this can become a transit channel for venous/arterial emboli, also known as paradoxical embolism. it can lead to a variety of clinical conditions such as stroke with an increase of twice the risk of death and disability in the long term (3). paradoxical embolism is defined as the passage of a thrombus from the venous circulatory system to the systemic circulation. for it to occur, specific clinical conditions, such as the following, must be fulfilled (4): 1. in the majority of cases, it is associated with the presence of risk factors that increase the likelihood of occurrence such as hypercoagulable states, recent post-operation states, being bedridden for prolonged periods, and having a history of neoplastic diseases of malignant etiology. 2. an anatomical communication between the venous system and the systemic circulation is required, as well as patent foramen ovale or defects in the septum at the atrial septum level. 3. lastly, it is conditioned by an increase of the pressure gradient from right to left, as are valsalva maneuvers. for a proper definition, paradoxical embolism is the incidental this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e46 manifestation of a venous thrombosis with a pulmonary embolism associated with a systemic embolism; which clinically presents itself in the vast majority of cases as an ischemic cerebrovascular event that may be acute or transitory. the patent foramen ovale can be found in about 30% of patients with ischemic cerebrovascular disease as an only finding (1). its prevalence appears to decrease with an increase in age, with an incidence of 34% during the first 3 decades of life, 25% between the third and seventh decade, and less than 20% in the octogenarian stage (5). the risk of paradoxical embolism was revised in the rope study which marks a large collaborative effort to pool research on cryptogenic stroke and patent foramen ovale. outcome events have been adjudicated so that recurrent stroke can be modeled excluding those with a non-patent foramen ovale related mechanism (6). the treatment for secondary prevention is unknown. antiplatelet therapy and oral anticoagulants in single or combined therapy can be used. warfarin aspirin recurrent stroke study (warss) with a population of 2206, was a double-blind randomized multicenter study that compared acetylsalicylic acid with warfarin in the prevention of ischemic cerebrovascular event. regardless of the presence of patent foramen ovale, there was no significant difference between warfarin and acetylsalicylic acid (7). patent foramen ovale in cryptogenic stroke study (piccs), another randomized multi-centered study evaluated 630 patients to compare warfarin (inr 1.4 2.8) and acetylsalicylic acid (325mg/mg) in patients with patent foramen ovale and stroke. it was noted that there is no significant difference between the two treatment strategies. however, the absolute risk for death or ischemic stroke was reduced by approximately half with the use of warfarin compared with acetylsalicylic acid in the subgroup of patent foramen ovale (8). in both studies, there was more presence of minor bleeding in the vitamin k antagonist group. in our specific case, oral anticoagulants are the first measure given that the need for thrombolysis in patients with acute pulmonary embolism without hypotension nor shock, places it as an intermediate-low risk and would only be implemented in a selected population. however, as of this moment, tracers that help define which patients will benefit from thrombolysis do not exist. individual tracers of right ventricular dysfunction and myocardial injury have an insufficient positive predictive value for complications and decision-making with regard to this therapy (9). the pulmonary embolism thrombolysis (peitho) study determined the effectiveness and safety of early thrombolytic therapy in normotensive patients with right ventricular dysfunction, detected in an echocardiographic scan or through a computerized axial tomography, or evidence of cardiac ischemic injury through proof of positive troponin (10). however, this study showed that the thrombolytic therapy prevented the hemodynamic decompensation in the future, and increases the risk of severe bleeding and hemorrhagic cerebrovascular disease. which in the clinical context of our patient was highly probable due to the presence of recent ischemic cerebrovascular disease and the prior orthopedic surgery. with these findings, the next step was to determine the risk stratification in subgroups to know if they benefited from the early recanalization therapy through the administration of fibrinolytic treatment. the study conducted by bova et al. demonstrated that three stages (i, ii, iii) were identified through the calculation of a seven-point risk index, which showed rates of complications related with pulmonary embolism after 30 days at 4.2%, 10.8% and 29.2%, respectively (11). again, the risk in our patient was raised, calculating a stage iii bova index, which in view of the presented evidence, defined the need of our patient to undergo thrombolytic therapy to prevent complications and mortality in the next 30 days. however, this would be applicable to patients with only thrombus pulmonary embolism and there is no solid evidence in patients with paradoxical embolism and much less in ischemic stroke. therefore, for future studies, it is necessary to validate this data and issue suggestions with solid medical evidence in this type of patient, as observed in our case report. 4. appendix 4.1. acknowledgements we wish to thanks sections of thoracic imaging and neuroradiology, fundacion santa fe de bogota hospital, bogota, colombia. 4.2. author’s contribution the author passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest none. 4.4. funding none. references 1. gupta v, yesilbursa d, huang wy, aggarwal k, gomez c, patel v, et al. patent foramen ovale in a large population of ischemic stroke patients: diagnosis, age distribution, gender, and race. echocardiography (mount kisco, ny). 2008;25(2):217-27. 2. heuchan am, clyman ri. managing the patent ductus arteriosus: current treatment options. archives this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alejandro avila et al. 4 of disease in childhood fetal and neonatal edition. 2014;99(5):f431-6. 3. omar h, huang c, miller j, mangar d, kabemba a, camporesi e. simultaneous pulmonary embolism and cerebrovascular stroke. herz. 2013;38(8):884-6. 4. podrouzkova h, horvath v, hlinomaz o, bedan j, bambuch m, nemec p, et al. embolus entrapped in patent foramen ovale: impending paradoxical embolism. the annals of thoracic surgery. 2014;98(6):e151-e2. 5. windecker s, stortecky s, meier b. paradoxical embolism. journal of the american college of cardiology. 2014;64(4):403-15. 6. kent d, thaler d. the risk of paradoxical embolism (rope) study: developing risk models for application to ongoing randomized trials of percutaneous patent foramen ovale closure for cryptogenic stroke. trials. 2010;12:185-. 7. mohr j, thompson j, lazar rm, levin b, sacco rl, furie k, et al. a comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. new england journal of medicine. 2001;345(20):1444-51. 8. homma s, sacco rl, di tullio mr, sciacca rr, mohr j, investigators picss. effect of medical treatment in stroke patients with patent foramen ovale patent foramen ovale in cryptogenic stroke study. circulation. 2002;105(22):2625-31. 9. jimenez d, aujesky d, moores l, gomez v, marti d, briongos s, et al. combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism. thorax. 2011;66(1):75-81. 10. meyer g, vicaut e, danays t, agnelli g, becattini c, beyer-westendorf j, et al. fibrinolysis for patients with intermediate-risk pulmonary embolism. new england journal of medicine. 2014;370(15):1402-11. 11. bova c, sanchez o, prandoni p, lankeit m, konstantinides s, vanni s, et al. identification of intermediaterisk patients with acute symptomatic pulmonary embolism. european respiratory journal. 2014;44(3):694703. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion: appendix references archives of academic emergency medicine. 2023; 11(1): e44 or i g i n a l re s e a rc h comparing the efficacy of long spinal board, sked stretcher, and vacuum mattress in cervical spine immobilization; a method-oriented experimental study wijittra liengswangwong1, natcha lertviboonluk1, chaiyaporn yuksen1∗, thanakorn laksanamapune1, weerawat limroongreungrat2, atipong mongkolpichayaruk2, kittichai tharawadeepimuk2, parunchaya jamkrajang2, prayoot sook-oum1, sorawich watcharakitpaisan1 1. department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, thailand. 2. college of sports science and technology, mahidol university, thailand. received: april 2023; accepted: may 2023; published online: 12 june 2023 abstract: introduction: inadequate spinal motion restriction in patients suffering from spinal injuries could lead to further neurological damage, ultimately worsening their prognosis. this study aimed to investigate the efficacy of long spinal boards (lsb), ske stretcher, and vacuum mattress for cervical spine immobilization during transportation of patients by measuring the angular motion of the cervical spine following lifting, transferring, and tilting. methods: we conducted an experimental study using a box of three randomizations and crossover designs without a washout period effect for the long spinal board, sked stretcher, and vacuum mattress. we concealed the randomization with sequentially numbered, opaque, sealed envelopes (snose). kinematic data were collected using eight optoelectronic cameras at 200 hz (bts bioengineering, milan, italy) in triangular planes (lateral bending, flexion-extension, and axial rotation) while performing all three motions (static lift-hold, transfer, and 90° tilt). results: 12 cases (7 males and 5 females) with the mean age of 20 ± 3.03 (range: 18-28) years were studied. the three highest angular motions were observed in the axial rotation plane during patient’s tilting under immobilization on all devices (vacuum mattress having the highest value of 99.01±8.93, followed by the lsb at 89.89±34.35 and the sked stretcher at 86.30±7.73 degrees). during patient lifting, a higher angular motion was observed with vacuum mattress immobilization in flexion extension (coefficient = 4.45; 95%ci: 0.46 – 8.45; p =0.029) and axial rotation (coefficient = 3.70; 95%ci: 0.58 – 6.81; p =0.020) planes. during patient transfer, a higher angular motion was observed with sked stretcher in the flexion-extension plane (coefficient = 2.98; 95%ci: 0.11 – 5.84; p = 0.042). during patient tilting to 90 degrees, a higher angular motion was observed with vacuum mattress immobilization in lateral bending (coefficient = -4.08; 95%ci: -7.68 -0.48; p = 0.026) for the vacuum mattress. conclusion: based on the finding of the present study, patients on the vacuum mattress experience significantly higher angular motion in flexion extension and axial rotation during lifting, as well as lateral bending during 90-degree tilting. in addition, patients on the sked stretcher showed significantly higher angular motion in flexion-extension during the transferring. however, the predictive margins for immobilization across all devices did not demonstrate clinically significant differences among the three immobilization devices. keywords: cervical vertebrae; motion; immobilization; stretcher; vacuum mattress cite this article as: liengswangwong w, lertviboonluk n, yuksen c, laksanamapune t, limroongreungrat w, mongkolpichayaruk a, tharawadeepimuk k, jamkrajang p, sook-oum p, watcharakitpaisan s. comparing the efficacy of long spinal board, sked stretcher, and vacuum mattress in cervical spine immobilization; a method-oriented experimental study. arch acad emerg med. 2023; 11(1): e44. https://doi.org/10.22037/aaem.v11i1.2036. ∗corresponding author: chaiyaporn yuksen; department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, 270 rama vi road, thung phaya thai, ratchathewi, bangkok, thailand, 10400. email: chaipool0634@hotmail.com, orcid: https://orcid.org/0000-0002-48907176. 1. introduction approximately 55% of spinal injuries involve the cervical region, and improper management of patients with potential spinal injuries can result in additional neurological damage, worsening their prognosis (1, 2, 3). in emergency departments, a minimum of 5% of patients with spinal injuries exhibit the emergence of neurological symptoms or this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index w. liengswangwong et al. 2 experience a decline in their condition. the determination to immobilize the spine is based on patient assessment and an evaluation of the trauma mechanics at the scene, while the decision to perform cervical imaging relies on clinical evaluation (2). in a prehospital setting, spinal immobilization is indicated for cases involving a high mechanism of injury, which heightens the likelihood of head or spinal injuries (3). the indications for cervical immobilization are often based on guidelines such as those provided by the national association of emergency medical technicians (naemt) and the prehospital trauma life support (phtls) program. the indications for cervical immobilization generally include a high mechanism of injury with potential cervical spine involvement, altered mental status, neurological deficits, pain or tenderness in the cervical region, and inability to self-extricate or move without assistance (4, 5). nowadays, there are many patient transport equipment for patients with suspected cervical spine injury (6). long spinal boards (lsb) have been a cornerstone of prehospital immobilization protocols for decades. lsb is typically rigid plastic, with straps and head immobilization devices to secure the patient during transportation. spinal boards have long served as a standard solution for prehospital patient immobilization (7). the findings of the studies indicate that implementing a spinal motion restriction (smr) protocol without the use of a lsb does not lead to a higher occurrence of spinal cord injuries (sci) (8, 9). however, there was no high-level evidence to support or refute the use of lsb in patients with suspected cervical spine injury (10). the sked stretcher comprises durable, high-density polyethylene plastic with multiple attachment points for securing patients and incorporating various configurations. it is compact, lightweight, and easily stored, making it an ideal solution for remote or challenging environments. the stretcher can be adapted for use in various emergency scenarios, including confined spaces, water and ice rescues, vertical or high-angle extractions, and hazardous materials incidents. vacuum mattresses consist of an air-impermeable cover filled with polystyrene beads, incorporated with straps and handles for secure patient immobilization and transportation. the beads conform to the patient’s body by removing air from the mattress, providing a customized fit and immobilization. vacuum mattresses effectively immobilize, reducing the risk of further injury during transportation. studies have demonstrated their superiority in spinal immobilization compared to traditional backboards and distributing pressure evenly, reducing discomfort and the risk of pressure ulcers (11). this study aimed to investigate the efficacy of lsb, ske stretcher, and vacuum mattress for cervical spine immobilization during transportation of patients by measuring the angular motion of the cervical spine following lifting, tranferring, and tilting. 2. methods 2.1. study design and setting this study was a method-oriented experimental study with a cross-over design, conducted from april 6, 2022, to may 25, 2022, at the department of emergency medicine, ramathibodi hospital, mahidol university, to compare the angular motion of cervical spine (flexion extension, axial rotation, and lateral bending) during lifting, transferring, and 90degree tilting of patients. mahidol university, a public institution in thailand, is situated in the salaya sub-district of phutthamonthon district, nakhon pathom province. the testing was conducted in a randomized crossover, with each participant assigned a random sequence using the lsb, sked stretcher, and vacuum mattress, without a washout period between each sequence. the study was designed such that there were 4 participants for each sequence. volunteer recruitment was facilitated by posting invitation posters within the university premises and scheduling appointments for interested individuals to participate in the study. none of the data used in this study revealed the volunteer’ identities. we replaced the volunteers’ names with their research id numbers. the study was approved by the human research ethics committee, faculty of medicine ramathibodi hospital, mahidol university (coa. mura2021/725). 2.2. participants the eligibility criteria of this study included adult volunteers aged 18-60, with a height range of 150-190 cm. exclusion criteria for the study were pre-existing spine deformities such as scoliosis, kyphosis, flatback syndrome, chin-on-chest syndrome, prior spine injury, and obesity with bmi of 30 kg/m2 or above. all eligible volunteers were stabilized with a cervical collar and head immobilization before being randomized to be studied using any of the three devices. 2.3. data gathering for all eligible study participants, various variables were recorded, including baseline characteristics such as age, gender, body mass index (bmi), height, and weight, as well as medical comorbidities and prior medical histories, such as diabetes mellitus, dyslipidemia, asthma, and allergic rhinitis, prior history of surgery, and prior history of trauma. additionally, the angular motion (lateral bending, flexionextension, and axial rotation) during lifting, transferring, and tilting with lsb, sked stretcher, and vacuum mattress was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e44 recorded. 2.4. angular motion analysis we used a 3-dimensional (3d) motion analysis system (bts bioengineering (smart dx 5000, italy)) to capture and analyze human body movement in three dimensions (figure 1). the bts smart dx 5000 system consisted of infrared cameras, reflective markers, and synchronized data capture. the smart dx camera uses infrared light to track reflective markers strategically placed on the subject’s body. reflective markers were attached to the mid-forehead, mid-upper anterior chest (sternal notch), and middle-of-the-lowest rib (figure 1). these markers help the infrared cameras track the movement of the subject’s body. the software system used complex algorithms to reconstruct the 3d coordinates of the reflective markers, creating a digital representation of the subject’s body movement. the participants were assigned to lift, transfer, and tilt in a box of three randomizations and crossover designs. we used only one volunteer in all procedures for each of the three devices including lsb, sked stretcher, and vacuum mattress (figure 2). each participant underwent three procedures, including liftings, transferring, and tilting. we concealed the randomized sequence with sequentially numbered, opaque, sealed envelopes (snose). angular displacements were measured at the cervical spine motion in three planes (lateral bending, flexion-extension, rotation) by a 3d motion analysis system while performing all three movements. four participants assumed positions at each corner of the transportation equipment, facing it with their feet shoulderwidth apart. they bent their knees and maintained a straight back to ensure proper lifting posture. each participant grasped the equipment using a power grip with both hands. a designated team leader coordinated the lift, ensuring everyone moves in unison. the team leader provided a verbal countdown to synchronize the lift. all participants lifted the equipment simultaneously, utilizing their legs to generate power while keeping their backs straight (lifting procedure). upon lifting the transportation equipment, the participants moved together in a coordinated manner, covering a distance of 2 meters while maintaining the equipment’s stability and level position (transfer procedure). the team then executed another verbal countdown to synchronize the lowering of the equipment to the floor. all participants bent their knees and lowered the equipment smoothly and in unison. lastly, two individuals grasped the equipment and jointly tilted it to a 90-degree angle (tilting procedure). 2.5. outcome measures the outcome of interest was angular motion of cervical spine in three planes (lateral bending, flexion extension, rotation) figure 1: dx camera (left) and the reflective markers attached on the volunteer’s body (right). by a 3d motion analysis system while performing all three movements. 2.6. statistical analysis statistical analyses were performed with stata version 16.0. we used numbers, mean, and standard deviation for the descriptive variables. for the analytic statistics, chi-square was applied when calculating the p-values of the cervical angle in three planes. a p-value ≤ 0.05 was considered significant. the coefficient mixed-effects multilevel regression was applied to compare the angle of motion between the vacuum mattress, sked, and lsb, and the lsb was the standard reference (the coefficient was 1). the sample size estimation was determined based on the study by etier be jr. et al. (12), which compared cervical spine motion following immobilization using a long spine board and a vacuum mattress. in their findings, the mean peak motion ranged from 12.5° to 14.0° for the lsb and from 11.4° to 15.4° for the vacuum mattress. with a significance level (alpha) of 0.10 and a power (1beta) of 95% for a onesided test, the estimated sample size was 32. currently, no evidence supports a universally acceptable angular motion restriction for the cervical spine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index w. liengswangwong et al. 4 table 1: angular motion after immobilization on a long spinal board, sked stretcher, or vacuum mattress motion planes of motion median (iqr) min max mean ± sd long spinal board lifting lateral bending 5.48 (4.28, 7.50) 2.23 11.96 6.34±3.00 flexion-extension 7.95 (7.46, 12.05) 5.93 19.30 9.70±3.72 axial rotation 8.26 (7.66, 10.85) 6.36 19.33 9.63±3.49 transfer lateral bending 5.10 (3.50, 7.10) 2.23 11.35 5.60±2.49 flexion-extension 7.30 (2.63, 10.70) 2.30 15.35 7.50±4.49 axial rotation 8.20 (6.50, 10.66) 5.26 19.80 9.60±4.52 tilting lateral bending 10.55 (8.65, 12.84) 5.45 30.00 13.10±7.94 flexion-extension 6.65 (5.23, 10.94) 4.03 95.80 20.31±32.06 axial rotation 97.73 (88.93, 105.46) 18.10 135.50 89.89±34.35 sked stretcher lifting lateral bending 5.46 (3.60, 6.86) 2.61 12.53 6.43±3.71 flexion-extension 12.15 (7.97, 14.75) 4.37 15.25 11.17±4.09 axial rotation 9.63 (7.20, 17.06) 4.54 22.40 12.08±6.05 transfer lateral bending 5.86 (4.10, 6.16) 3.83 9.55 5.83±1.81 flexion-extension 8.50 (7.60, 12.75) 5.70 19.35 10.52±4.22 axial rotation 9.80 (6.50, 10.90) 4.03 20.65 9.75±5.03 tilting lateral bending 13.66 (9.40, 15.50) 5.60 18.20 12.58±4.08 flexion-extension 5.60 (5.05, 7.50) 4.00 31.40 8.92±8.61 axial rotation 84.06 (83.30, 87.05) 79.60 105.70 86.30±7.73 vacuum mattress lifting lateral bending 6.38 (4.77, 10.07) 3.42 32.67 9.45±8.56 flexion-extension 11.33 (9.17, 14.75) 4.29 35.00 13.74±8.93 axial rotation 13.87 (11.67, 14.47) 4.67 22.03 13.04±4.99 transfer lateral bending 4.43 (4.40, 6.23) 2.96 11.55 6.05±3.25 flexion-extension 9.35 (5.30, 13.23) 3.36 20.66 10.33±5.56 axial rotation 11.60 (8.30, 14.70) 7.10 18.70 11.65±4.05 tilting lateral bending 9.05 (5.70, 10.95) 3.80 15.60 8.57±3.48 flexion-extension 7.15 (5.90, 8.00) 3.40 24.46 8.61±5.71 axial rotation 99.20 (95.60, 105.45) 82.60 115.03 99.01±8.93 min: minimum; max: maximum; sd: standard deviation; iqr: interqurtile range. 3. results 3.1. baseline characteristics of participants the participants for this study included 12 cases (7 males and 5 females) with the mean age of 20 ± 3.03 (range: 18-28) years and bmi of approximately 21.02 ± 2.15 kg/m2. one participant had a history of trauma but no prior spinal injury. 3.2. angular motion of cervical spine table 1 summarizes the angular motions of cervical spine after immobilization on lbs, sked stretcher, and vacuum mattress during patient’s lifting, transferring and tilting. the results showed a wide range of angular motion, ranging from 2.23 to 135.5 degrees. the three highest angular motions were observed in the axial rotation plane during patient’s tilting under immobilization on all devices (vacuum mattress having the highest value of 99.01±8.93, followed by the lsb at 89.89±34.35 and the sked stretcher at 86.30±7.73 degrees). the three lowest angular motions were observed in the lateral bending plane during patient transfer using all devices (lsb having the lowest value of 5.60±2.49, followed by the sked stretcher at 5.83±1.81, and the vacuum mattress at 6.05±3.25 degrees). findings indicate that patient’s tilting causes the most angular c-spine motion in all planes, particularly in the axial rotation plane. table 2 and figure 3 compare the angular motion of cervical spine during lifting, transferring, and tilting after immobilization on lsb, sked stretcher, and vacuum mattress. 3.3. patient lifting during patient lifting, a higher angular motion was observed with vacuum mattress immobilization in flexion extension (coefficient = 4.45; 95%ci: 0.46 – 8.45; p =0.029) and axial rotation (coefficient = 3.70; 95%ci: 0.58 – 6.81; p =0.020) planes. however, the predictive margins of immobilization did not differ clinically in the angular motion of flexion extension and axial rotation planes during lifting with all devices as shown in figure 4. 3.4. patient transfer during patient transfer, a higher angular motion was observed with sked stretcher in the flexion-extension plane (cothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e44 figure 2: evaluating the three fixation devices, namely spinal board, sked strecher, and vacuum mattress during lifting, transfering and tilting of patients. efficient = 2.98; 95%ci: 0.11 – 5.84; p = 0.042). however, the predictive margins of immobilization did not differ clinically in the angular motion of the flexion-extension plane during transfer with all devices as shown in figure 5. 3.5. patient tilting during patient tilting to 90 degrees, a higher angular motion was observed with vacuum mattress immobilization in lateral bending (coefficient = -4.08; 95%ci: -7.68 -0.48; p = 0.026) for the vacuum mattress. however, the predictive margins of immobilization did not differ clinically in the angular motion of the lateral bending plane during tilting with all devices as shown in figure 6. 4. discussion this study employed a dynamic simulation system to evaluate the efficacy of three immobilization devices including lsb, vacuum mattress, and sked stretcher, in limiting cervical spine movement across three planes. the spinal board is the standard device for immobilization. based on the finding of the present study, patients on the vacuum mattress experience significantly higher angular motion in flexion extension and axial rotation during lifting, as well as lateral bending during 90-degree tilting. in addition, patients on the sked stretcher showed significantly higher angular motion in flexion-extension during the transferring. however, the predictive margins for immobilization across all devices did not demonstrate clinically significant differences among the three immobilization devices. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index w. liengswangwong et al. 6 figure 3: box plot of cervical angular motions based on immobilization devices. figure 4: margins plots of angular motion of flexion-extension and axial rotation planes during lifting after immobilization on long spinal board, sked stretcher and vacuum mattress. ci: confidence interval. a previous study by johnson et al. used healthy volunteers with no injury to compare the comfort, speed, and ability to immobilize the lsb versus the vacuum mattress. the vacuum mattress was faster and more comfortable, but the lsb was better at controlling head movement. (13) the lsb increases pressure ulcer incidence and severity compared with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e44 table 2: comparison of angular motion of neck during lifting, transferring, and tilting after immobilization on long spinal board, sked stretcher, and vacuum mattress based on coefficient mixed-effects multilevel regression angular motion type devices coefficient 95% ci p -value during lifting lateral bending vacuum mattress 3.15 -1.16, 7.46 0.152 sked stretcher 0.15 -4.30, 4.60 0.948 long spinal board reference flexion extension vacuum mattress 4.45 0.46, 8.45 0.029 sked stretcher 1.95 -2.36, 6.26 0.376 long spinal board reference axial rotation vacuum mattress 3.70 0.58, 6.81 0.020 sked stretcher 3.10 6.99, 12.27 0.060 long spinal board reference during transferring lateral bending vacuum mattress 0.45 -1.63, 2.53 0.671 sked stretcher 0.28 -1.82, 2.36 0.797 long spinal board reference flexion extension vacuum mattress 2.70 -0.09, 5.50 0.058 sked stretcher 2.98 0.11, 5.84 0.042 long spinal board reference axial rotation vacuum mattress 1.80 -0.97, 4.58 0.203 sked stretcher -0.13 -2.97, 2.70 0.926 long spinal board reference during tilting lateral bending vacuum mattress -4.08 -7.68, -0.48 0.026 sked stretcher -0.09 -3.94, 3.77 0.965 long spinal board reference flexion extension vacuum mattress -8.35 -18.97, 2.27 0.123 sked stretcher -9.96 -21.38, 1.47 0.088 long spinal board reference axial rotation vacuum mattress 7.58 -6.57, 21.72 0.294 sked stretcher -5.77 -20.90, 9.37 0.455 long spinal board reference ci: confidence interval. figure 5: margins plots of angular motion of flexion-extension plane during transfer after immobilization on long spinal board, sked stretcher and vacuum mattress. ci: confidence interval. vacuum mattresses (14). the findings of study by prasarn ml et al. were in favor of using vacuum mattress versus lsb alone in preventing motion figure 6: margins plots of the relation between angular motion of lateral bending plane during tilting after immobilization on long spinal board, sked stretcher and vacuum mattress. ci: confidence interval. at an unstable cervical spine injury (11). in the study by nolte pc et al. with one healthy male, using this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index w. liengswangwong et al. 8 a vacuum mattress during transportation resulted in twofold as much motion of the cervical spine compared to a spine board (15). these findings are in line with the results of the studies by rahmatalla et al. and mahshidfar et al., who found more cervical motion with a vacuum mattress during transportation (16, 17). given that the predictive margins for immobilization among the long spinal board, vacuum mattress, and sked stretcher have not shown clinically significant cervical spine movement differences, we advise implementing a customized approach when choosing transport equipment for individual patients. the long spinal board is widely accessible and costeffective, making it a standard option for emergency medical services. due to its buoyancy and durability, it is easy to clean, decontaminate, and can be employed in diverse environments, including water rescues. the sked stretcher, with its versatile and compact design, facilitates effortless transportation and storage. it is suitable for confined spaces, rugged terrains, and vertical rescues. additionally, the vacuum mattress offers greater patient comfort than long spinal boards and sked stretchers, owing to its adaptable nature, and it minimizes the risk of pressure ulcers and discomfort during prolonged transport times. it conforms to the patient’s body shape, providing tailored support and immobilization, and is compatible with various settings, including helicopter evacuations, due to its lightweight design and ease of use. each immobilization device has its benefits. the long spinal board is a cost-effective and widely available option that provides rigid support. the sked stretcher is versatile and suitable for various rescue scenarios, while the vacuum mattress offers enhanced patient comfort and customized immobilization. the choice of the device will depend on the specific needs and constraints of the emergency and the patient’s condition. 5. limitations the study population consisted of 12 volunteers, less than the calculated sample size. we had limits on the force and the people who transported the volunteers, and we changed the person the next day of the experiment. some random sequences were alternated because of the reflective markers attached to the transport device, which wasted the time of the new installation. the subjects were healthy and fully conscious adults of average height and weight. thus, results may not be generalizable to all adults and special population patients, such as pediatric patients (18), as they have physical characteristics and needs that may require different immobilization methods. motion capture system using eight optoelectronic cameras bts bioengineering (smart dx 5000, italy) had limited ability to capture some direction due to obscure camera, which may have affected the results. finally, this study focused solely on lifting, transferring, and tilting procedures. additionally, the study participants were volunteer from mahidol university, which may limit the results’ generalizability (external validity) when applied to emergency medical services. 6. conclusion based on the finding of the present study, patients on the vacuum mattress experience significantly higher angular motion in flexion extension and axial rotation during lifting, as well as lateral bending during 90-degree tilting. in addition, patients on the sked stretcher showed significantly higher angular motion in flexion-extension during the transferring. however, the predictive margins for immobilization across all devices did not demonstrate clinically significant differences among the three immobilization devices. 7. declarations 7.1. acknowledgments the authors would like to thank all participating staff and volunteers. furthermore, we thank the team from the college of sports science and technology, mahidol university. 7.2. conflict of interest the authors declare that they have no competing interests. 7.3. fundings no funding was obtained for this study. 7.4. authors’ contribution all authors made a significant contribution to the work reported, whether that is in conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. all authors read and approved the final version. 7.5. ethical considerations this study was approved by the faculty of medicine, committee on human rights related to research involving human subjects, ramathibodi hospital, mahidol university (coa. mura2021/725). 7.6. availability of data and material the datasets used and/or analyzed during the current study are avilable form the corresponding author on reasonable request. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e44 7.7. using artificial inteligence chatbots none. references 1. athinartrattanapong n, yuksen c, leela-amornsin s, jenpanitpong c, wongwaisayawan s, leelapattana p. prediction 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münzberg m, rittmann a, et al. analysis of cervical spine immobilization during patient transport in emergency medical services. eur j trauma emerg surg. 2021;47(3):719-26. 16. rahmatalla s, deshaw j, stilley j, denning g, jennissen c. comparing the efficacy of methods for immobilizing the cervical spine. spine (phila pa 1976). 2019;44(1):3240. 17. mahshidfar b, mofidi m, yari ar, mehrsorosh s. long backboard versus vacuum mattress splint to immobilize whole spine in trauma victims in the field: a randomized clinical trial. prehosp disaster med. 2013;28(5):462-5. 18. rozzelle cj, aarabi b, dhall ss, gelb de, hurlbert rj, ryken tc, et al. management of pediatric cervical spine and spinal cord injuries. neurosurgery. 2013;72 suppl 2:205-26. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e23 or i g i n a l re s e a rc h two-stage clinical model for screening the suspected cases of acute ischemic stroke in need of imaging in emergency department; a cross-sectional study somayeh karimi1, lorraine martins dutra e oliva2, hosein rafiemanesh3,4, melissa mendez capitaine5, sarah jabre6, alireza baratloo7,8∗ 1. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 2. school of medicine, nove de julho university (uninove), sao paulo, brazil. 3. non-communicable diseases research center, alborz university of medical sciences, karaj, iran. 4. department of epidemiology and biostatistics, school of public health, alborz university of medical sciences, karaj, iran. 5. department of emergency medicine, la villa general hospital, health secretary, mexico city, mexico. 6. department of emergency medicine, jackson memorial hospital, miami, florida, usa. 7. research center for trauma in police operations, directorate of health, rescue & treatment, police headquarter, tehran, iran. 8. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: december 2022; accepted: january 2023; published online: 20 february 2023 abstract: introduction: just as failure to diagnose an acute ischemic stroke (ais) in a timely manner affects the patient’s outcome; an inaccurate and misplaced impression of the ais diagnosis is not without its drawbacks. here, we introduce a two-stage clinical tool to aid in the screening of ais cases in need of imaging in the emergency department (ed). methods: this was a multicenter cross-sectional study, in which suspected ais patients who underwent a brain magnetic resonance imaging (mri) were included. the 18 variables from nine existing ais screening tools were extracted and a two-stage screening tool was developed based on expert opinion (stage-one or rule in stage) and multivariate logistic regression analysis (stage-two or rule out stage). then, the screening performance characteristics of the two-stage mode was evaluated. results: data from 803 patients with suspected ais were analyzed. among them, 57.4% were male, and their overall mean age was 66.9 ± 13.9 years. there were 561 (69.9%) cases with a final confirmed diagnosis of ais. the total sensitivity and specificity of the two-stage screening model were 99.11% (95% ci: 98.33 to 99.89) and 35.95% (95% ci: 29.90 to 42.0), respectively. also, the positive and negative predictive values of two-stage screening model were 78.20% (95% ci: 75.17 to 81.24) and 94.57% (95% ci: 89.93 to 81.24), respectively. the area under the receiver operating characteristic (roc) curve of the two-stage screening model for ais was 67.53% (95% ci: 64.48 to 70.58). overall, using the two-stage screening model presented in this study, more than 11% of suspected ais patients were not referred for mri, and the error of this model is about 5%. conclusion: here, we proposed a 2-step model for approaching suspected ais patients in ed for an attempt to safely exclude patients with the least probability of having an ais as a diagnosis. however, further surveys are required to assess its accuracy and it may even need some modifications. keywords: decision support techniques; emergency service, hospital; stroke; diagnosis, differential cite this article as: karimi s, dutra e oliva lm, rafiemanesh h, mendez capitaine m, jabre s, baratloo a. two-stage clinical model for screening the suspected cases of acute ischemic stroke in need of imaging in emergency department; a cross-sectional study. arch acad emerg med. 2023; 11(1): e23. https://doi.org/10.22037/aaem.v11i1.1941. ∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. tel: +989122884364, email: arbaratloo@sina.tums.ac.ir / alirezabaratloo@yahoo.com, orcid: https://orcid.org/0000-0002-4383-7738. 1. introduction acute ischemic stroke (ais) is the most common neurological disorder with a disabling element in the world. it is considered a multifactorial disease, with incidence tending to increase with advancing age (1). world health organization (who) statistics indicate that all types of strokes are ranked this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karimi et al. 2 as the third cause of death (13-15%) and were surpassed only by heart disease and cancer (2). since early diagnosis has a special value in terms of treatment efficacy and prognosis in modern emergency practices, several clinical tools are currently in use, which aim to establish ais diagnosis, mostly in a prehospital setting (3-6). an ideal tool is one that combines the ability to screen positive cases with precise exclusion, in addition to the ease of applicability; while the evaluation of current tools demonstrates high sensitivity and median specificity (7), which implies a considerable amount of flawed diagnoses. it is noteworthy that such inaccurate diagnoses lead to increase in expenses for the patients and health systems with subsidiary tests, and may also delay the correct diagnosis and its required management (8-10). another factor that may necessitate designing a new clinical tool with desirable sensitivity and specificity for diagnosis of ais is the latest pandemic of covid-19. among wellestablished post-covid comorbidities, the state of hypercoagulability after infection is a consolidated issue. this clinical condition has been reported as an aggravation of covid19, which could enhance the pathological mechanism of ais, and consequently, further increase the incidence of ais. this emphasizes the importance of accurate care in emergency departments (eds) to achieve satisfactory outcomes (11-14). importantly, inaccurate raising of ais diagnosis leads to unnecessary tests, imaging, and consults that may prolong the ed length of stay, which are recommended to be avoided, especially during the pandemic. this could be considered as an additional reason for need of an accurate clinical tool for ruling out ais in eds. we believe that, just as failure to diagnose an ais in a timely manner affects the patient’s outcome, an inaccurate and misplaced impression of ais diagnosis is not without drawbacks and may even be associated with significant problems. therefore, we decided to introduce a novel clinical tool to aid in terms of screening ais patients, in need of further evaluation in the ed. this tool may help identify the patients who do not need emergency imaging and neurological consultation. 2. methods 2.1. study design and setting this was a diagnostic accuracy study, in which we decided to introduce a new scoring system for screening of ais patients in need of imaging in the ed. this study was approved by the ethical committee of tehran university of medical sciences (ir.tums.chmc.rec.1401.128). informed consent was obtained from all the subjects and/or their legal guardian(s) of the patients, and it was explained that all methods were performed in accordance with the relevant guidelines. it should be mentioned that we did not interfere with the patients’ management process, and just used the recorded data, so no additional costs were imposed neither on the patients, nor on the system. 2.2. study population this study was a multicenter survey in which, all patients who were referred to the ed of four educational hospitals in tehran, isfahan, and ahvaz, in iran during the year 2020 and for whom a brain magnetic resonance imaging (mri) was performed with suspicion of ais, after the evaluation of an in-charge physician, were included. patients with a history of any known neurological disease, head trauma, previous neurological surgery, and those who had left the ed against medical advice before undergoing brain mri were excluded. assuming a prevalence of at least 50% of ais in suspected patients referring to the hospitals’ ed, as well as examining a maximum of 25 variables for the new stroke screening tool and considering at least 10 patients for each variable, we needed at least 500 patients to design a model. also, considering two-thirds of the samples for model design and onethird of the samples for testing, we needed another 250 patients. therefore, to meet the objective of this study, in total, the minimum required sample size was determined to be 750 patients. 2.3. data collection all data were gathered by an emergency medicine resident under the supervision of an emergency medicine specialist. data were collected using a pre-prepared checklist consisting of three sections. the first section of the checklist included baseline characteristics and demographics of the patients including age, gender, past medical history, drug history, and the time of symptom onset. the second part included physical examination findings of 18 variables from nine existing ais screening tools [cincinnati pre-hospital stroke scale (cpss), face-arm-speechtime (fast), los angeles pre-hospital stroke screening (lapss), medic prehospital assessment for code stroke (med pacs), melbourne ambulance stroke screen (mass), ontario pre-hospital stroke screening (opss), pre-hospital ambulance stroke test (prehast), rapid arterial obstruction evaluation (race), recognition of stroke in the emergency room (rosier)]. these nine tools are validated stroke scales used to diagnose ais in pre-hospital and hospital settings. the third part included the final diagnosis of the patients, all of which were made based on the interpretation of their brain mri, which was considered the gold standard for the diagnosis of ais in this study. the brain mri scans were interpreted by a radiologist and/or a neurologist. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e23 2.4. modeling and statistical analysis modeling for the new criterion was done in two stages. in the first stage, based on the experts’ opinion, the clinical criteria that the person should be referred for further investigation of the imaging were determined. at this stage, the best model was selected among the two models obtained based on the percentage of correct classification of patients. the patients who were not positive for these clinical criteria met the criteria for entering the second part of the screening or rule-out model, which is a statistical model. in the statistical model, based on the available variables (except for the variables of the first stage), a multivariable model was designed for the rule-out of patients. the data were described as frequency and percentage or mean and standard deviation (sd), as appropriate. the frequency distribution of variables in each criterion was compared between patients with and without stroke using a chisquare test. in addition, an univariable logistic regression analysis was conducted for all variables presented in all nine stroke screening tools and other independent variables. the new screening tool was developed based on multivariable logistic regression analysis. results were presented as odds ratios (or) with 95% confidence intervals (ci) and p-values. a p-value <0.05 was considered statistically significant. also, we calculated sensitivity, specificity, positive (ppv ) and negative predictive value (npv ) as well as area under the receiver operating characteristic (roc) curve with 95%ci for the twostage screening model. all analyses were performed using stata software version 14, college station, tx: statacorp llc. 3. results 3.1. baseline characteristics of participants in this study, data from 803 patients with suspected ais were analyzed (57.4% male). the mean age of the studied participants was 66.9 ± 13.9 years. the diagnosis of ais was finally confirmed for 561 (69.9%) cases. table 1 compares the baseline characteristics as well as 18 extracted variables from 9 studied tools between cases with and without confirmed ais. 3.2. developing the two-stage clinical screening model stage one (rule-in stage) among the nine tools examined in this study, some variables are examined in most tools, like “speech or aphasia”, which is present in all tools except lapss, while some were examined in only one or two tools, such as “terminally ill or palliative care patient” only in opss or “commands (one or noncorrect)” and “sensory (pain)” only in pre-hast tool (table 2). based-on expert opinion, among the 18 assessed variables from 9 tools, 5 variables from 4 different tools were selected such that if a patient met any, they would need further evaluation with emergent brain imaging. the criteria “arm drift or weakness/hand grip” from cpss and “leg weakness/drift” from med pacs overlapped with “unilateral arm/leg weakness or drift” from opss; thus, two models were conceived for the initial screening (rule-in), one with 3 variables and the other with 4 variables. combination of 3 variables included “facial droop or palsy”, “speech disturbance or aphasia”, and “unilateral arm/leg weakness or drift”; combination of four variables included “facial droop or palsy”, “speech disturbance or aphasia”, “arm drift or weakness/hand grip”, and “leg weakness/drift”. the percentage of correct classification of ais (83.06% vs 82.69%) as well as or (25.30 (95%ci: 15.75 – 40.65) vs 24.71 (95%ci: 15.28 – 39.95)) of the three-variable model were higher than the four-variable model. therefore, the three-variable model was selected for the first stage of patient screening. based on the three-variable model, 647 patients (80.6%) were considered positive for ais, of which 111 (17.16%) were false positives. figure 1 shows the venn diagram of variables for screening positive cases, in need of imaging. out of 647 patients, 250 (38.64%) cases were positive for all 3 criteria. also, 46 (41.44%) cases out of the 111 false positive patients, had two or three positive variables. -stage two (rule-out stage) based on the remaining variables of the 9 studied tools (14 variables), a model for screening negative patients was designed. based on the univariate logistic regression analysis, male gender (or=2.76), history of cerebral vascular accident (cva) (or=3.93), and being a smoker (or=3.30), were the strongest predictors of ais in negative patients remaining from the first stage of screening. also, “symptoms of the stroke have resolved” (or=2.64, p=0.076), and “visual field defect” (or=11.30, p=0.052) were marginally significant (table 1). a multivariable model was performed to design a screening criterion (table 3). the model obtained in the backward wald approach showed the best performance based on 4 variables: “cva history”, “smoking”, “symptoms of the stroke have resolved” and “visual field defect”. “cva history”, “smoking, “symptoms of the stroke have resolved” were attributed scores of 1 while “visual field defect” a score of 2. based on this scale and a cut-off point score less than 1 (figure 2), 92 patients were diagnosed as negative (11.46% of the total patients), only 5 (0.62% of the total patients) of which had a false negative result. in other words, the probability of ais among patients who were negative in all four variables in the second stage of screening was equal to 5.43%. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karimi et al. 4 table 1: comparing the baseline characteristics as well as extracted variables from 9 studied tools between cases with and without confirmed acute ischemic stroke (ais) variable total final diagnosis of ais or (95%ci) p yes (n=562) no (n=244) baseline characteristics age>45 years 1 143 (91.7) 118 (90.1) 25 (100) >100 (na) 0.999 sex, male 74(47.4) 57(43.5) 17(68.0) 2.76 (1.11-6.84) 0.029 history of cva 22(14.1) 14(10.7) 8 (32.0) 3.93 (1.44-10.76) 0.008 history of htn 108 (69.2) 90(68.7) 18(72.0) 1.17 (0.45-3.02) 0.744 history of ihd 46(29.7) 39(30.0) 7 (28.0) 0.91 (0.35-2.35) 0.841 smoker 32(20.5) 22(16.8) 10(40.0) 3.30 (1.31-8.31) 0.011 stage one variables facial droop or palsy 342 (42.5) 311 (55.3) 31 (12.8) 8.43 (5.58-12.73) <0.001 speech disturbance or aphasia 512 (63.6) 440 (78.3) 72 (29.6) 8.57 (6.09-12.04) <0.001 unilateral arm/leg weakness or drift 537 (66.8) 469 (83.6) 68 (28.0) 13.12 (9.17-18.77) <0.001 arm drift or weakness/ hand grip 511 (63.5) 449 (79.9) 62 (25.5) 11.60 (8.14-16.54) <0.001 leg weakness/drift 501 (62.2) 441 (78.5) 60 (24.7) 11.11 (7.80-15.84) <0.001 stage two variables seizure or epilepsy absent 147 (94.2) 123 (93.9) 24(96.0) 1.56 (0.19-13.06) 0.681 symptoms of the stroke have resolved 20(12.8) 14(10.7) 6 (24.0) 2.64 (0.90-7.71) 0.076 blood glucose between 50 and 400 mg/dl 131 (94.2) 109 (94.0) 22(95.7) 1.41 (0.17-12.07) 0.752 blood sugar < 4mmol/l 1(0.7) 1(0.9) 0(0.0) 0.0 (na) 1.0 loss of consciousness or syncope 11 (7.1) 8(6.1) 3 (12.0) 2.01 (0.52-8.52) 0.301 glasgow coma scale <10 0(0.0) 0(0.0) 0(0.0) na patient is not wheelchair bound or bedridden 151 (96.8) 127 (96.9) 24(96.0) 0.76 (0.08-7.06) 0.806 head and gaze deviation 1(0.6) 1(0.8) 0(0.0) 0.0 (na) 1.0 symptom duration less than 24-25 hours 107 (69.0) 88(67.7) 19(76.0) 1.51 (0.56-4.06) 0.413 terminally ill or palliative care patient 1(0.6) 1(0.8) 0(0.0) na 1.0 visual field defect 3(1.9) 1(0.8) 2(8.0) 11.30 (0.98-129.83) 0.052 commands (none or non-correct) 1(0.6) 1(0.8) 0(0.0) 0.0 (na) 1.0 sensory (pain) 0: normal 137 (87.8) 117 (89.3) 20 (80.0) 1.0 0.161 1: apprehends less or different on one side 18(11.5) 13 (9.9) 5 (20.0) 2.25 (0.72-7.0) 0.306 2: apprehends only on one side 1(0.6) 1(0.8) 0(0.0) 0.0 (na) 1.0 ci: confidence interval. cva: cerebral vascular accident, htn: hypertension, ihd: ischemic heart disease, or: odds ratio; ci: confidence interval. 3.3. screening performance characteristics of the two-stage model the sensitivity and specificity of stage-one were 95.54% (95% ci: 93.84 to 97.25) and 54.13% (95% ci: 47.85 to 60.41), and for stage-two they were 80.0% (95% ci: 64.32 to 95.68) and 66.41% (95% ci: 58.32 to 74.50), respectively. the total sensitivity and specificity of two-stage screening model were 99.11% (95% ci: 98.33 to 99.89) and 35.95% (95% ci: 29.90 to 42.0), respectively. also, the positive and negative predictive values of the two-stage screening model were 78.20% (95% ci: 75.17 to 81.24) and 94.57% (95% ci: 89.93 to 81.24), respectively. the area under the roc curve of the two-stage screening model for ais was 67.53% (95% ci: 64.48 to 70.58). overall, using the two-stage screening model presented in this study, more than 11% of suspected ais patients were not referred for mri, and the error of this model is about 5%. 4. discussion in light of the importance of clinical applicability and cost efficiency for the worldwide healthcare systems, this study was conducted to create a helpful ais screening tool for the ed physicians. the objective of our study was not to help achieve a final diagnosis as we already have the tools to diagnose an ais; as there are multiple stroke scales that are validated, and further guidance is needed in terms of which items to look for when deciding which patients need to undergo immediate imaging and neurological consult (15, 16). in this study, we suggested a two-stage model for approaching suspected ais patients in ed to attempt to safely exclude patients with the least probability of having an ais as a diagnosis. first, patients who satisfy none of the criteria including “facial droop or palsy”, “speech disturbance or aphasia” or “unilateral arm/leg weakness or drift criteria” were selected for the second stage of the study, while those who this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e23 table 2: the variables of nine studied tools variable lapss cpss fast opss med pacs mass race pre-hast rosier facial droop or palsy xa x x x x x x arm drift or weakness/hand grip x xb x x c x x speech or aphasia x x x x x x x x seizure x x x x x symptoms of the stroke have resolved xd blood glucose between 50 (or 60) and 400 mg/dl x x x leg weakness/drift x x x blood sugar < 4mmol/l x d consciousness or syncope x x patient is not wheelchair bound or bedridden x x head & gaze deviation x x x age>45 years x x symptom duration less than 24-25 hours x x unilateral arm/leg weakness or drift x e x x terminally ill or palliative care patient x visual field defect x x commands (one or non-correct) x sensory (pain) x cincinnati pre-hospital stroke scale (cpss), face-arm-speech-time (fast), los angeles pre-hospital stroke screening (lapss), medic prehospital assessment for code stroke (med pacs), melbourne ambulance stroke screen (mass), ontario pre-hospital stroke screening (opss), pre-hospital ambulance stroke test (pre-hast), rapid arterial obstruction evaluation (race), recognition of stroke in the emergency room (rosier). a. facial paralysis or arm strength weakness; b. arm weakness (left/ right); c. have two items, arm drift and hand grip; d. exclusion criterion; e. facial paralysis or arm strength weakness. figure 1: the venn diagram of the three-variable model (stage one of the two-stage screening model) for screening of suspicious acute ischemic stroke cases in need of imaging in emergency department. met any of these three criteria required emergent brain imaging. the second stage of the study consisted of using a scoring system based on 4 criteria: “history of cva” (score=1), “smoking” (score=1), “symptoms of the stroke have resolved” (score=1), and “visual field defect” (score=2). using this scale and considering a cut-off point score of less than 1, the diagnosis of ais would be very unlikely based on the results of our study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karimi et al. 6 figure 2: the flowchart of the proposed two-stage model performance in the study population. true positive: needs imaging/confirmed acute ischemic stroke (ais); false positive: needs imaging/not ais (waste imaging); true negative: does not need imaging/not ais (ais ruled out correctly); false positive: does not need imaging/confirmed ais (missed cases). cva: cerebral vascular accident. table 3: the multivariate logistic regression analysis of independent predictors of acute ischemic stroke in patients without symptoms of stage one variables variable model 1 model 2 model 3 or (95%ci) p or (95%ci) p or (95%ci) p male gender 2.49 (0.83-7.48) 0.105 3.14 (1.14-8.66) 0.027 cva history 3.08 (1.02-9.25) 0.045 3.67 (1.28-10.51) 0.015 3.43 (1.16-10.11) 0.025 smoker 3.04 (0.98-9.39) 0.053 4.20 (1.43-12.32) 0.009 symptoms resolved 4.62 (1.32-16.22) 0.017 4.67 (1.37-15.95) 0.014 visual field defect 32.25 (2.30-452.65) 0.010 29.32 (2.28-376.54) 0.010 19.61 (1.48-259.37) 0.024 possible score 0 to 4 0 to 4 0 to 5 model 1: enter, model 2: forward wald, model 3: backward wald. cva: cerebral vascular accident, or: odds ratio, ci: confidence interval. it is well known that, in dealing with an ais patient, “time is brain” (2, 17). indeed, any patient suspected of having ais should be transported to the nearest hospital with staff experienced in ais management and emergency brain imaging as quickly and safely as possible (17-19). but before that, how do we quickly rule out ais? this is where the importance of exclusion criteria and this new tool described is reflected. we intended to eliminate unnecessary imaging, tests, and consults, which lead to high expenses and increase ed length of stay in those for whom ais can be easily and safely eliminated from the list of differential diagnoses (20-22). however, it is always mandatory to perform a complete neurological examination, once the patient presents with symptoms such as dizziness, paresthesia, deviation of the labial commissure, dysphagia, weakness of any limb, difficulty in or loss of vision; among many others, to alert the clinician to look for various neurological causes (2, 19, 23). some patients with stroke who receive tpa may re-canalize and have a negative mri. this may happen spontaneously as well. these patients would be predicted to have a stroke using the derived model on the basis of “symptoms of stroke have resolved” (e.g. score > 1 on step 2) but would be considered as stroke “negative” using the criteria for presence or absence of stroke used in this study (positive mri). thus, they this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e23 would show up as false positives. it is just as important to accurately identify these patients as for complete strokes since they need the same evaluation and institution of appropriate secondary prevention strategies. the use of mri as the sole criterion of diagnostic accuracy, ignores the reality of false negative mri for acute stroke, which may particularly occur with small, early, brainstem lesions, especially if there is artifact or the dwi sequence is not optimized for contrast-to-noise. again, biasing the model against small or brainstem strokes. 5. limitations this work is not the end, but the beginning and the gateway for future analysis, patients from other continents can be integrated, and the classification and clinical criteria can be adjusted according to the population studied. since each stroke scale used in this study has been elaborated by a different country or city, the risk factors may thus vary epidemiologically. another limitation is the consensus made to identify a clinical tool, without modifying the absolute reliability of the new scale and therefore, improving its specificity. 6. conclusions in this study, we suggested a two-stage model for approaching suspected ais patients in ed to attempt to safely exclude patients with the least probability of having ais as the diagnosis. first, patients who satisfy none of the criteria including “facial droop or palsy”, “speech disturbance or aphasia” or “unilateral arm/leg weakness or drift criteria” were selected for the second step of the study, while those who met any of these three criteria required emergent brain imaging. the second stage of the study consisted of using a scoring system based on 4 criteria: “history of cva” (score=1), “smoking” (score=1), “symptoms of the stroke have resolved” (score=1), and “visual field defect” (score=2). a patient with a true stroke would be missed in only 0.6% (5/803) of cases if applying the two-stage screening tool on a suspected ais patients presenting to the ed, at the expense of 19.3% (155/803) false positive stroke identifications. however, further surveys are required to assess its accuracy and it may even need some modifications. 7. declarations 7.1. acknowledgments we would like to express our commitment and appreciation to the prehospital and hospital emergency research center affiliated with tehran university of medical sciences. 7.2. conflict of interest the authors declare that there is no conflict of interest. 7.3. fundings and supports this study has been funded and supported by tehran university of medical sciences (grant no: 1401-2-101-58900). 7.4. authors’ contribution the conception and design of the work by all the authors; data acquisition by sk and ab; analysis and interpretation of data by hr and ab; drafting the work by sk, lmdo and mmc; revising it critically for important intellectual content by hr, sj and ab; all the authors approved the final version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work. references 1. adeoye o, nyström kv, yavagal dr, luciano j, nogueira rg, zorowitz rd, et al. recommendations for the establishment of stroke systems of care: a 2019 update: a policy statement from the american stroke association. stroke. 2019;50(7):e187-210. 2. yaria j, gil a, makanjuola a, oguntoye r, miranda jj, lazo-porras m, et al. quality of stroke guidelines in lowand middle-income countries: a systematic review. bull 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of posterior circulation stroke in the emergency setting. front neurol. 2021;12:682827. 9. liberman al, prabhakaran s. stroke chameleons and stroke mimics in the emergency department. curr neurol neurosci rep. 2017;17(2):15. 10. goldstein lb, simel dl. is this patient having a stroke? jama. 2005;293(19):2391-402. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karimi et al. 8 11. saberian p, seyed-hosseini-davarani s-h, ramezani m, mirbaha s, zangi m, aarabi s. concomitant covid19 and acute ischemic stroke in patients transferred by emergency medical service during first wave of pandemic in tehran, iran; a cross-sectional study. front emerg med. 2022;6(2):e23. 12. belani p, schefflein j, kihira s, rigney b, delman b, mahmoudi k, et al. covid-19 is an independent risk factor for acute ischemic stroke. am j neuroradiol. 2020;41(8):1361-4. 13. qureshi ai, baskett wi, huang w, shyu d, myers d, raju m, et al. acute ischemic stroke and covid-19: an analysis of 27 676 patients. stroke. 2021;52(3):905-12. 14. hassett c, gedansky a, mays m, uchino k. acute ischemic stroke and covid-19. cleve clin j med. 2020;87(12):19-21. 15. alijanpour s, mostafazdeh-bora m, ahangar aa. different stroke scales; which scale or scales should be used? caspian j intern med. 2021;12(1):1-21. 16. bandini f, vestito l, filippi l. prehospital scales in acute ischaemic stroke management. lancet neurol. 2021;20(7):504. 17. mendelson sj, prabhakaran s. diagnosis and management of transient ischemic attack and acute ischemic stroke: a review. jama. 2021;325(11):1088-98. 18. zubair as, sheth kn. emergency care of patients with acute ischemic stroke. neurol clin. 2021;39(2):391-404. 19. meyran d, cassan p, avau b, singletary e, zideman da. stroke recognition for first aid providers: a systematic review and meta-analysis. cureus. 2020;12(11):e11386. 20. zhelev z, walker g, henschke n, fridhandler j, yip s. prehospital stroke scales as screening tools for early identification of stroke and transient ischemic attack. cochrane database syst rev. 2019;4(4):cd011427. 21. atallah am, zurrú m, alonzo c, ameriso s, cirio j, zurrú m. consensus statement on diagnosis and treatment of acute ischemic stroke stroke council-argentine society of cardiology. rev argent cardiol. 2012;80:394-404. 22. choreño-parra ja, carnalla-cortés m, guadarrama-ortíz p. ischemic cerebrovascular disease: extensive review of the literature for the first contact physician. med interna mex. 2019;35(1):61-79. 23. gibbons i, williams o. bet 2: fast or rosier to identify suspected stroke in the prehospital setting? emerg med j. 2020;37(9):586-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references emergency. 2017; 5 (1): e64 le t t e r to ed i to r emergency department readmission rate within 72 hours after discharge; a letter to editor hassan barzegari1, mohammad ali fahimi1∗, schwann dehghanian1 1. department of emergency medicine, golestan general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: march 2017; accepted: april 2017; published online: 3 april 2017 cite this article as: barzegari h, fahimi ma, dehghanian s. emergency department readmission rate within 72 hours after discharge; a letter to editor. 2017; 5(1): e64 there are several factors that lead to early return of patients to the medical centers. these could be due to latent illnesses, misdiagnosis or even inadequate medical care due to staff being worn out (1, 2). determining the mentioned factors could help decrease the rate of readmission, restore patient’s confidence in health centers and decrease the cost of medical care. chi lung wu et al. in 2010 sought to find out the major cause of patients’ return within 24 hours after discharge from emergency department (ed) and showed that abdominal pain and fever were the most common causes of patients’ return, respectively. they found that, on average, 5.5% of discharged patients returned to the hospital (3). tazhibi et al. carried out a research to find out major causes of readmission in alzahra hospital, isfahan, iran, and concluded that factors related to the patient and hospital could be held responsible for the patients’ readmission to the studied hospital (1). verelst s et al., investigating the reasons for patient re-hospitalization within 72 hours after discharge in a teaching hospital in belgium, found that 1.9% of admissions to the ed were in fact readmissions. 12% of this population were readmitted because of misdiagnosis, (2). chang sy et al. carried out a research in a teaching hospital in taiwan to investigate the reasons for non-traumatic patient readmission within 72 hours of their discharge. they reported the rate of 3.5% for their readmissions out of their overall 72000 visits. misdiagnosis was the most common problem among patients who had been readmitted shortly after discharge (4). in a retrospective cross-sectional study, we evaluated the medical profiles of all patients who were readmitted within 72 hours of their discharge from the ed of golestan hospital, ∗corresponding author: mohammad ali fahimi; emergency department, imam khomeini general hospital, azadegan avenue, ahvaz, khuzestan province, iran. postal code: 6193673166 tel/fax: +986112229166 email: fahimi76@yahoo.com . ahvaz, iran, during july to december 2013, aiming to find the readmission rate of this ed. 63736 patients were admitted to the ed during the 6-month study period, 635 (0.99%) cases of which were readmitted within the first 72 hours of discharge (67.1% male). 338 (53.2%) were 16 – 45 years old. traumatic injuries (37.1%), flank pain (8.3%), acute coronary syndrome (7.2%), cerebro-vascular accident (5.2%), and abdominal pain (4.8%) were among the most frequent causes of previous ed visit of readmitted patients. finally, 70.2% of these patients were discharged again, 15.7% were admitted to other hospital wards, and 14.1% were transferred to other hospitals. comparing the results of the present study with previous ones indicates that readmission rate can vary widely not only among different countries but also among various hospitals of the same country. for instance, in the studied hospital, which is a trauma center in the region, readmission rate of trauma patients is higher. since readmissions cause unnecessary overcrowding in ed, it would be best if each hospital evaluated their rate of readmission and its causes, and then tried to relieve the problems found. this can be effective in better management of ed, reduction of treatment costs, increasing patient satisfaction, and prevention of ed overcrowding. references 1. tazhibi m, ghaderi nl, tirani m. causes of readmission of patients to alzahra hospital, iran. health system research. 2011;7(1):101 7. 2. verelst s, pierloot s, desruelles d, gillet j-b, bergs j. short-term unscheduled return visits of adult patients to the emergency department. the journal of emergency medicine. 2014;47(2):131-9. 3. wu c-l, wang f-t, chiang y-c, chiu y-f, lin t-g, fu l-f, et al. unplanned emergency department revisits within 72 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. barzegari et al. 2 hours to a secondary teaching referral hospital in taiwan. the journal of emergency medicine. 2010;38(4):512-7. 4. cheng s-y, wang h-t, lee c-w, tsai t-c, hung c-w, wu k-h. the characteristics and prognostic predictors of unplanned hospital admission within 72 hours after ed discharge. the american journal of emergency medicine. 2013;31(10):1490-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 22 emergency (2015); 3 (1): 22-26 original research rectal thiopental versus intramuscular ketamine in pediatric procedural sedation and analgesia; a randomized clinical trial reza azizkhani, mehrdad esmailian, azadeh shojaei*, keihan golshani department of emergency medicine, isfahan university of medical sciences, isfahan, iran *corresponding author: azadeh shojaei; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989136470851; fax: +983117923445; email: dr.shojaeiazadeh@yahoo.com received: july 2014; accepted: september 2014 abstract introduction: physicians frequently deal with procedures which require sedation of pediatric patients. laceration repair is one of them. no study has been performed regarding the comparison between induction of sedation with sodium thiopental and ketamine in laceration repair. therefore, the present study was aimed to comparison of induced sedation by rectal sodium thiopental and muscular injection of hydrochloride ketamine in pediatric patients need laceration repair. methods: the presented study is a single-blinded clinical trial performed through 2013 to 2014 in ayatollah kashani and alzahra hospitals, isfahan, iran. patients from 3 months to 14 years, needed sedation for laceration repair, were entered. patients were sequentially evaluated and randomly categorized in two groups of hydrochloride ketamine with dose of 2-4 milligram per kilogram and sodium thiopental with dose of 25 milligram per kilogram. demographic data and vital signs before drug administration and after induction of sedation, ramsey score, time to onset of action, and sedation recovery time were evaluated. chi-squared, mann-whitney, and non-parametric analysis of covariance tests were used. p<0.05 was considered as a significant level. results: in this study 60 pediatric patients were entered. 30 patients with mean age of 42.8±18.82 months were received sodium thiopental and the rest with mean age of 30.08±16.88 months given ketamine. mann-whitney test was showed that time to onset of action in sodium thiopental group (28.23±5.18 minutes) was significantly higher than ketamine (7.77±4.13 minutes), (p<0.001). the sedation recovery time in ketamine group (29.83±7.70) was higher than sodium thiopental. depth of sedation had no significant difference between two groups based on ramsey score (p=0.87). no significant difference was seen between two groups in the respiratory rate (df=1, 58; f=0.002; p=0.96) and heart rate (df=1, 58; f=0.98; p=0.33). however, arterial oxygen saturation level (df=1, 58; f=6.58; p=0.013) was significantly higher in ketamine group. conclusion: the findings of the present study show that although the recovery time from sedation by ketamine is more than sodium thiopental, it’s fast-acting function without effecting on the oxygen saturation level causes that ketamine is considered as the better choice for induction of sedation in pediatric patients need laceration repair. in addition, long-term effect of ketamine provides more time for the physician to do the procedure and this issue decreases the need probability to the repeated-dose. however, effectiveness of both drugs to decrease the agitation was equal, based on the ramsey score. key words: hypnotics and sedatives; barbiturates; thiopental; ketamine cite this article as: azizkhani r, esmailian m, shojaei a, golshani k. rectal thiopental versus intramuscular ketamine in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2015;3(1):22-6. introduction: hysicians frequently deal with procedures which require sedation of pediatric patients. these procedures include a range from painless interventions like imaging to painful therapeutic interventions such as reduction of fracture, laceration repair, bone marrow aspiration, and central catheter insertion (1, 2). also, presenting in unfamiliar places as operation room, unpleasant odor, performing of painful techniques, and etc. all cause to increase the mental stress, restlessness, and agitation of the children as well as lack of their cooperation with medical staffs. these reactions not only intervene with performing required therapies, but also lead to some changes in physiologic parameters such as blood pressure, heart rate, and respiratory rate (3, 4). so, choosing the right medication has a critical role in such cases. an appropriate sedative drug causes to reduce the p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 23 emergency (2015); 3 (1): 22-26 needed dosage and increase the safety of procedure (5). many of these drugs have different routes of administration and choosing the best one is varied based on the type of procedure, pain level, depth of sedation required, and patient's status (1, 6, 7). laceration repair is one of the procedures in which addition to painfulness, the child suffer from a high agitation and stress. thus, in such situations a procedural sedation and analgesia should be used (1, 7). several drugs have been suggested to this purpose, while each of them has some side effects that limit their use in different clinical conditions. these side effects have a wide range from cardiovascular and respiratory systems to kidney and central nervous system. in addition, the main routes of administration of these drugs are intravenous that lead to some difficulties for using them in children (8, 9). ketamine is one of the sedative drugs which has been used in pediatric patients for a long time. it has both sedative and analgesic features based on which it can be solitary used for painful procedures. ketamine has been suggested as a sedative premedication in pediatric patients and recognized as a safe drug which has minimum side effects on cardiovascular and respiratory systems. ketamine cause the lidocaine injection and suture handling to be well-tolerated for children in conditions which laceration repair is needed (10). however, some side effects when used by intramuscular route, such as delayed recovery from sedation cause to use it cautiously (11). sodium thiopental, as a rapid-onset short-acting barbiturate general anesthetic, is another sedative drug applied for pediatric patients. this drug is in the list of essential drugs in each therapeutic center, declared by world health organization (who) (12). although it’s cardiovascular and respiratory side effects are more than ketamine, it has rapid recovery from sedation (13). however, no study has been performed regarding the comparison between induction of sedation with sodium thiopental and ketamine in laceration repair. therefore, the present study was aimed to comparison of induced sedation by rectal sodium thiopental and muscular injection of hydrochloride ketamine in pediatric patients need laceration repair. methods: study design and setting the presented study is a randomized single-blind clinical trial performed through october 2013 to june 2014 in ayatollah kashani and alzahra hospitals, isfahan, iran. the study protocol was confirmed by ethical committee of esfahan university of medical sciences. all researches observed helsinki protocol during their assessments and drug administration. the written informed consent was given from parents of children. the study was registered in iranian registry of clinical trial (irct number: irct2015043012072n4). subject in this research pediatric patients, from 3 months to 14 years, needed sedation for laceration repair were entered. exclusion criteria were sensitivity to sodium thiopental or barbiturates, persistent asthma, severe cardiovascular disease, porphyria, contraindications to the use of rectal medications (inflammatory, hemorrhagic, and neoplastic lesions in the intestine), children with airway infection, coronary artery disease, head trauma, eye trauma, central nervous system disease, any contraindications to receive sedation, and lack of parents' consent. also, each event causes to stopping the procedure and lacking of response to rectal sodium thiopental administration, with maximum dose of 40 mg/kg, led to exclude the subject, too. patients are sequentially allocated and with considering the minimum and maximum of standard deviation 15 and 3 minutes for persisting of sedation, α=0.05 and β=0.1, and the maximum error of 1.5 minutes (d=1.5), about 28 subjects were appropriate in each group (1, 7, 12). therapeutic intervention patients were randomly categorized in two groups of hydrochloride ketamine with dose of 2-4 milligram per kilogram (mg/kg) (dissolved in 10 milliliter of distilled water for muscular administration) and sodium thiopental with dose of 25 mg/kg, maximum dose of 1 gram for each child, (dissolved in 10 milliliter of distilled water for rectal administration). randomization was done as permuted-block randomization using computerized software. drugs were purchased from rotexmedia company (germany). because of difference routes of administration for these two drugs, it was not possible to do the study as double-blind. thus, the administering researcher was aware from the type of drug. to remove examiner bias, data was gathered by another researcher who was blind to the group of drug administration. for suture handling, lidocaine (3-5 mg/kg of body weight as local injection) without bicarbonate and epinephrine was used to relieve the pain. the drugs were injected when arterial oxygen saturation was above 95%. in case of any drop in oxygen saturation, nasal cannula and oxygen therapy masks were used to delivery of 100% oxygen. in presenting of ketamine side effects, midazolam with dose of 0.05 mg/kg of body weight was used (dissolved in 5 milliliter distilled water as intravenous for 2 minutes). variables ramsey score was applied to assess the induced sedation. its scale is distributed from 1 (restless and agitation in the patient) to 6 (lacking of any response) (14). the aim of induced sedation was reaching to the score of 4 (brisk response of the subject to light glabella tap or loud auditory stimulus). the time to onset of action (from administration to reach the ramsey score of 4) and seda this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com azizkhani et al 24 tion recovery time (from ramsey score 4 to full consciousness of the child) were assessed. furthermore, demographic data (age, gender), vital signs (respiratory rate, heart rate, and arterial oxygen saturation level) before drug administration and after induction of sedation (reaching to ramsey score of 4) were also evaluated. at the end, the presence of any side effect related to the administration of assessed drugs was recorded. statistical analysis data were entered to spss version 21.0. quantitative variables were presented as mean and standard deviation and qualitative ones as frequency and percentage. to assess the difference between two studied groups regarding demographic and clinical factors before therapeutic intervention chi-squared test (for nominal qualitative variables) and mann-whitney test (for quantitative and ordered variables) were used. the comparison of these groups for time to onset of action and sedation recovery time, mann-whitney test was applied, too. since vital signs of pediatric patients before drug administration in two groups had significant difference, nonparametric analysis of covariance test was applied to compare such factors after the administration. in all analysis p<0.05 was considered as a significant level. results: in this study 60 pediatric patients were entered. 30 patients were received sodium thiopental and the rest ketamine. the mean age of children given sodium thiopental was 42.8±18.8 months and those received ketamine 30.10±16.88 months (p=0.01). 20 (66.7%) of patients in sodium thiopental group and 19 (63.3%) ones in ketamine group were male (p=0.79). the demographic and clinical variables of the patients is shown in table 1. in evaluating the vital signs of patients before therapeutic intervention, it was determined that respiratory rate (p<0.001), heart rate (p<0.001), and arterial oxygen saturation level (p<0.001) were higher in ketamine group (table 1). the time to onset of action in ketamine group was 7.77±4.13 minutes and in sodium thiopental 28.23±5.18 minutes (p<0.001). however, the sedation recovery time in ketamine group (29.83±7.70) was higher than sodium thiopental (12.57±2.57), (p<0.001). however, the depth of sedation based on ramsey score, has no significant difference between two groups (p=0.87). in evaluating vital signs after therapeutic intervention, no significant difference was seen between two groups in the respiratory rate (df=1, 58; f=0.002; p=0.96) and heart rate (df=1, 58; f=0.98; p=0.33). however, arterial oxygen saturation level (df=1, 58; f=6.58; p=0.013) was significantly higher in ketamine group (table 2). moreover, no side effect related to the administration of drugs was observed until discharging the patients. discussion: the findings of the present study show that the time to onset of action of sodium thiopental is significantly higher than hydrochloride ketamine, while its sedation recovery time is shorter. it is worth noting that the average of arterial oxygen saturation level in ketamine group was more than sodium thiopental (about 4%). as the result, although recovery time from ketamine sedation is more than sodium thiopental, it is considered as the better choice for induction of sedation in pediatric patients need laceration repair. in addition, long-term effect of ketamine provides more time for the physician to do the procedure and may reduce the need to repeat dose of medication. but, the effectiveness of both drugs for reducing the agitation is equal, based on ramsey score. the previous studies showed that using ketamine even with lower doses leads to induced sedation and acceptable analgesic effects. for example, majidinejad and colleagues displayed that lower dose of ketamine administration has similar effect to morphine in reducing the pain from broken bone (15). qureshi et al. showed in their study on 30 patients that taking ketamine orally causes the lidocaine injection and suture handling to be well-tolerated for the child (10). to comparison ketamine with nitrous oxide, lee and colleagues declared that nitrous oxide is a safer drug than ketamine injection, makes faster recovery, and does not induce unnecessarily deep sedation (7). in another research by jung et al. it was displayed that emergence agitation in pediatric patients need orthopedic surgery does not appear any difference between two groups of ketamine and sodium table 1: demographic and clinical variables in the studied patients variable therapeutic groups p1 ketamine thiopental age (month) 30.10±16.88 42.8±18.82 0.013 gender (%) male 19 (63.33) 20 (66.67) 0.792 female 11 (36.67) 10 (33.33) vital signs (before intervention) respiratory rate (per minute) 19.27±5.36 15.33±1.26 <0.001 heart rate (per minute) 106.87±15.64 96.47±4.11 <0.001 arterial oxygen saturation (%) 96.0±2.72 93.4±1.28 <0.001 1based on mann-whitney test 2 based on chi-squared test this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 25 emergency (2015); 3 (1): 22-26 thiopental (16). in addition, kim and others stated that intravenous injection and thiopental administration in preoperative holding area have the equal effectiveness in reducing the agitation of separation form parents and have no effect on emergence agitation. this study declared that using sodium thiopental could be a better choice for preanesthetic medication, if monitoring was accurately performed (17). in congruent, the present study shows that effectiveness of these two drugs is the same in reducing agitation of the child. in several other studies it was established that ketamine is more appropriate drug than sodium thiopental. for instance, yoosefi et al. presented that ketamine administration during electroconvulsive therapy is well-tolerated and leads to faster improving of depression signs, reduce the seizure following the therapy, and better cognitive function in comparison with sodium thiopental (18). furthermore, saadawy and others showed that for prevention from the pain of propofol administration, using ketamine is better than sodium thiopental (19). the findings of this study also displayed that using ketamine is the better choice for induction of sedation before suture handling in pediatric patients. one of the limitations of the present research was the few number of sample size in the studied groups, but it seems that this limitation has no effect on findings. it was determined that the least power of this project in assessing effectiveness and efficiency of ketamine and sodium thiopental was 87%. because the power of study was in appropriate, the low sample size has no effect on the findings of study. conclusion: the findings of the present study show that the time to onset of action of sodium thiopental is significantly higher than hydrochloride ketamine, while its sedation recovery time is shorter. it is worth noting that the average of arterial oxygen saturation level in ketamine group was more than sodium thiopental (about 4%). as the result, although recovery time from ketamine sedation is more than sodium thiopental, it is considered as the better choice for induction of sedation in pediatric patients need laceration repair. in addition, long-term effect of ketamine provides more time for the physician to do the procedure and may reduce the need to repeat dose of medication. but, the effectiveness of both drugs for reducing the agitation is equal, based on ramsey score. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of ayatollah kashani and alzahra hospitals, esfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria 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and analgesia in children. n engl j med. 2014;370(1):90-1. 6. krauss b, green sm. procedural sedation and analgesia in children. the lancet. 2006;367(9512):766-80. 7. lee jh, kim k, kim ty, et al. a randomized comparison of nitrous oxide versus intravenous ketamine for laceration repair in children. pediatr emerg care. 2012;28(12):1297table 2: the efficiency of ketamine and sodium thiopental in induction of sedation variable therapeutic groups p ketamine thiopental sedition times onset to action (minutes) 7.77±4.13 28.23±5.18 a<0.001 sedation recovery time (minutes) 29.83±7.70 12.57±2.57 a<0.001 ramsey score 3.70±0.60 3.70±0.60 a0.87 vital signs respiratory rate (per minute) 21.31±5.52 18.13±2.0 0.96b heart rate (per minute) 115.44±11.93 105.12±3.80 0.33c arterial oxygen saturation (%) 95.92±3.0 92.12±1.74 0.013d a based on mann-whitney test b based on non-parametric analysis of covariance test; adjusted for respiratory rate before intervention and age of the patient c based on non-parametric analysis of covariance test; adjusted for heart rate before intervention and age of the patient d based on non-parametric analysis of covariance test; adjusted for arterial oxygen saturation level before intervention and age of the patient this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com azizkhani et al 26 301. 8. song jh. procedural sedation and analgesia in children. j korean med assoc. 2013;56(4):271-8. 9. messeri a, astuto m. procedural sedation and analgesia in children. pediatric anesthesia, intensive care and pain: standardization in clinical practice: springer; 2013. p. 47-59. 10. qureshi f, mellis p, mcfadden m. efficacy of oral ketamine for providing sedation and analgesia to children requiring laceration repair. pediatr emerg care. 1995;11(2):93-7. 11. peña bm, krauss b. adverse events of procedural sedation and analgesia in a pediatric emergency department. ann emerg med. 1999;34(4):483-91. 12. o'brien jf, falk jl, carey be, malone lc. rectal thiopental compared with intramuscular meperidine, promethazine, and chlorpromazine for pediatric sedation. ann emerg med. 1991;20(6):644-7. 13. sacchetti a, schafermeyer r, gerardi m, et al. pediatric analgesia and sedation. ann emerg med. 1994;23(2):237-50. 14. consales g, chelazzi c, rinaldi s, de gaudio a. bispectral index compared to ramsay score for sedation monitoring in intensive care units. minerva anestesiol. 2006;72(5):329-36. 15. majidinejad s, esmailian m, emadi m. comparison of intravenous ketamine with morphine in pain relief of long bones fractures: a double-blind randomized clinical trial. emergency. 2014;2(2):77-80. 16. jung hj, kim jb, im ks, oh sh, lee jm. effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery. korean j anesthesiol. 2010;58(2):148-52. 17. kim hy, lee ws, seo wj, lee kc. the effect of intravenous ketamine versus thiopental in the preoperative holding area on the separation anxiety and emergence agitation in children. j anesthesiol. 2014;2(2):13-7. 18. yoosefi a, sepehri as, kargar m, et al. comparing effects of ketamine and thiopental administration during electroconvulsive therapy in patients with major depressive disorder: a randomized, double-blind study. j ect. 2014;30(1):15-21. 19. saadawy i, ertok e, boker a. painless injection of propofol: pretreatment with ketamine vs thiopental, meperidine, and lidocaine. middle east j anesthesiol. 2007;19(3):631-44. emergency. 2017; 5 (1): e81 http://dx.doi.org/10.22037/emergency.v5i1.18805 or i g i n a l re s e a rc h valsalva maneuver using a handmade device in supraventricular tachycardia reversion; a quasi experimental study maryam motamedi1, mohammad ali akbarzadeh2, saeed safari1, mehrnoosh shahhoseini1∗ 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. cardiovascular research center, modarres hospital, shahid beheshti university of medical sciences, tehran, iran. received: september 2017; accepted: october 2017; published online: 15 october 2017 abstract: introduction: the use of vagal nerve stimulation is identified as a proper treatment option in patients with stable supraventricular tachycardia (svt). this study aimed to assess the success of valsalva maneuver via a handmade device in reversion of svt. methods: in this quasi experimental study, using a handmade device, vagus nerve stimulation was performed for svt patients presenting to emergency department or cardiac intervention unit and the success rate and its related factors were assessed. results: 100 patients with the mean age of 53.05 ± 13.70 years were studied (67% female). 12 (12%) cases were unable to do the maneuver. out of the 88 (88.0%) patients who could perform the maneuver, 75 (85.2%) cases were unsuccessful. dysrhythmia was controlled in 6 (6.8%) cases on the first attempt and in 7 (8.0%) cases on the second one (14.8% total success rate). 12 of the 13 cases (92.3%) of successful maneuver had history of svt (p = 0.031). there was not any significant association between success rate and sex (p = 0.084), age (p = 0.744), or other medical histories (p ≥ 0.05). conclusion: based on the results of the present study, the success rate of valsalva maneuver with the mentioned handmade device was calculated to be 14.8%. the only independent related factor of successful reversion was svt history. keywords: vagus nerve stimulation; valsalva maneuver; tachycardia, supraventricular; arrhythmias, cardiac; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: motamedi m, akbarzadeh ma, safari s, shahhoseini m. valsalva maneuver using a handmade device in supraventricular tachycardia reversion; a quasi experimental study. emergency. 2017; 5(1): e81. 1. introduction s upraventricular tachycardia (svt) comprises a common group of cardiac arrhythmia in patients referring to emergency departments. the overall incidence of this acute phenomenon has been estimated to be 35 cases per 100,000 patients (1). svt symptoms are often nonspecific, which include chest pain, shortness of breath, sense of palpitation, pounding in the neck, and even some degree of psychological disturbances such as anxiety (2). impulse formation and impulse conduction processes may both be disturbed (3). in fact, three mechanisms of triggered activity, reentry, or ∗corresponding author: mehrnoosh shahhoseini; emergency department, shohadaye tajrish hospital, shardari street, tajrish square, tehran, iran. email: me.shahhoseini@gmail.com tel: 00989123072482 increased automaticity with atrioventricular node source or above cardiac tissue source may be involved in svt (4). hence, the initial management of svt involves slow atrioventricular node conduction by evolving pharmacological approaches, mechanical maneuvers, or invasive approaches if required (5-14). the use of vagal maneuvers is now identified as a proper treatment option for patients with stable svt but its success rate varies between 6% and 54% (15-19). there are different options for performing vagal maneuvers including the valsalva maneuver and carotid sinus massage (20). however, there is no measurable and controlled method in this regard. the present study aimed to assess the success of valsalva maneuver via a handmade device in reversion of svt. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. motamedi et al. 2 2. methods 2.1. study design and setting this quasi experimental multicenter study was performed from oct 2014 to oct 2016 at four general educational hospitals (imam hossein, shohadaye tajrish, loghman hakim, and modarres hospitals), tehran, iran. using a handmade device, vagus stimulation was performed for patients presenting to emergency department or cardiac intervention unit following svt. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences. all researchers adhered to principles of helsinki declaration and confidentiality of patients’ information. 2.2. participants the study was conducted on patients >18 years old who consecutively presented to emergency departments of the mentioned hospitals with the initial evidence of svt (n = 45) or were scheduled for inducing arrhythmia by a cardiologist at cardiac intervention unit (n = 55). patients who were not able to perform the maneuver or did not give consent, those with hemodynamic instability, atrial fibrillation or flutter, malignant hypertension, or other contraindications for performing valsalva maneuver (such as cerebral avm, increased intraocular pressure, glaucoma, or third trimester of pregnancy) were excluded. 2.3. procedure for creating the valsalva maneuver’s handmade device, the cuff of the sphygmomanometer was disconnected and the device’s pressure monitor was connected to a 90cm oxygen connector, and the end of connector was connected to a 10cc syringe (figure 1). maneuver was performed at supine position and with 30 to 50 mmhg pressure for 15 seconds. if the first attempt was unsuccessful, another attempt was made after five minutes. in cases of unsuccessful reversion with two valsalva maneuver, pharmacological approach was begun. during the maneuver performance, all required supportive instruments including intubation and defibrillation sets were available and the patients were under continuous cardiac and blood pressure monitoring. 2.4. outcome achieving sinus rhythm following the first or second maneuver attempt was considered as the main outcome of study (successful maneuver). 2.5. statistical analysis results were presented as mean ± standard deviation (sd) or frequencies and percentages. chi-square or fisher’s exact tests and t test were used for comparisons. data were analyzed using spss 21 statistical software. p values of 0.05 or figure 1: the handmade device used in the present study. table 1: baseline characteristics of the studied patients variable value sex female 67 (67) male 33 (33) age (year) 20 – 40 16 (16) 40 – 60 50 (50) ≥ 60 34 (34) medical history hypertension 17 (17) diabetes mellitus 19 (19) smoking 10 (10) ischemic heart disease 17 (17) svt 67 (67) arrhythmias 6 (6) calcium blocker use 11 (11) beta blocker use 45 (45) weight (kg) 73.8 ± 13.8 height (cm) 165.0 ± 8.2 heart rate (beats/minute) 173.3 ± 25.7 data were presented as mean ± standard deviation or number (%). svt: supraventricular tachycardia. less were considered statistically significant. 3. results 3.1. baseline characteristics 100 patients with the mean age of 53.05 ± 13.70 years (22 85) were studied (67% female). the baseline characteristics of the subjects are summarized in table 1. most patients were in the age range of 40 – 60 years and 67% of them had history of svt. svt had resulted from atrio-ventricular nodal reentrant tachycardia (avnrt) in 59%, atrio-ventricular reentrant tachycardia (avrt) in 14%, and unknown origin in 27%. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e81 3.2. maneuver outcome 12 (12%) cases were unable to do the maneuver. out of the 88 (88.0%) patients who could perform the maneuver, 75 (85.2%) cases were unsuccessful. dysrhythmia was controlled in 6 (6.8%) cases at the first attempt and in 7 (8.0%) cases at the second one (14.8% total success rate). 12 of the 13 cases (92.3%) of successful maneuver had history of svt (p = 0.031). there was not any significant association between success rate and sex (p = 0.084), age (p = 0.744), or other medical histories (p ≥ 0.05). unable and unsuccessful cases were treated with ablation (52.9%), adenosine (40.4%), amiodarone (4.5%), and verapamil (2.2%). 4. discussion based on the results of the present study, the success rate of valsalva maneuver with the introduced handmade device was estimated to be 14.8%. the only independent related factor of successful reversion was svt history. along with medications and ablation, the use of vagal maneuvers has been introduced as an alternative modality leading to reversion of avrt and avnrt in up to 54% of affected patients (17, 21). vagal maneuver can be the most successful method to reverse arrhythmias if the maneuver is performed in supine position with adequate intra-thoracic pressure (at least 30 mmhg) for at least 15 seconds (22, 23). despite considering all the mentioned conditions, the success rate of this maneuver has been considerably low in almost all studies. as shown in our study, the vagal maneuver was successful only in 14.8% of subjects. this rate was about 19.4% in the report by lim et al. (17). however, in animal and laboratory-based studies as well as in the new modified version of valsalva maneuver, the rate of reversion was shown to be in the range of 45.9% to 54.3% (1, 21). taylor et al. showed that only few number of physicians give enough instructions to their patients regarding the position, duration, pressure and other characteristics of maneuver (24). according to the second finding of our study, with respect to main determinants of the success of valsalva maneuver to reverse svt, none of the baseline characteristics, except for previous experiment of svt, could predict high success rate for this maneuver. higher success of this maneuver to terminate svt in those with previous svt might be due to more careful and cautious performance of the maneuver by the specialists in this high risk group or more excitability of cardiac conductive system of those cases by inducing maneuver. it seems that, a majority of patients who suffer from svt may not benefit from valsalva maneuver and thus, employing the modified maneuver is more recommended. higher success of this maneuver in patients with history of svt requires more evaluation. therefore, further studies with larger and heterogonous samples and proper follow up are recommended. 5. limitation in this study, more than half of the participants were patients with induced arrhythmia by cardiologist, which may affect the response to treatment. 6. conclusion based on the results of the present study, the success rate of valsalva maneuver with the mentioned handmade device was calculated to be 14.8%. the only independent related factor of successful reversion was svt history. 7. appendix 7.1. acknowledgements this article is derived from dr. mehrnoosh shahhoseini’s thesis for achieving a specialist degree in the field of emergency medicine at shahid beheshti university of medical sciences. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. orejarena la, vidaillet h, destefano f, nordstrom dl, vierkant ra, smith pn, et al. paroxysmal supraventricular tachycardia in the general population. journal of the american college of cardiology. 1998;31(1):150-7. 2. bibas l, levi m, essebag v. diagnosis and management of supraventricular tachycardias. cmaj: canadian medical association journal= journal de l’association medicale canadienne. 2016;188(17-18):e466. 3. al-zaiti ss, magdic ks. paroxysmal supraventricular tachycardia. critical care nursing clinics. 2016;28(3):309-16. 4. rujic d, sundboll j, tofig b, nielsen j, pareek m. initial evaluation and management of paroxysmal supraventricular tachycardia. ugeskrift for laeger. 2016;178(3). 5. sawan n, eitel c, thiele h. ablation supraventrikularer tachykardien. herzschrittmachertherapie+ elektrophysiologie. 2016;27(2):143-50. 6. page rl, joglar ja, 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termination of paroxysmal supraventricular tachycardia. circulation. 1998;98(24):2716-23. 17. lim s, anantharaman v, teo w, goh p, tan a. comparison of treatment of supraventricular tachycardia by valsalva maneuver and carotid sinus massage. annals of emergency medicine. 1998;31(1):30-5. 18. smith g. management of supraventricular tachycardia using the valsalva manoeuvre: a historical review and summary of published evidence. european journal of emergency medicine. 2012;19(6):346-52. 19. ferguson jd, dimarco jp. contemporary management of paroxysmal supraventricular tachycardia. circulation. 2003;107(8):1096-9. 20. sohinki d, obel oa. current trends in supraventricular tachycardia management. the ochsner journal. 2014;14(4):586-95. 21. taylor dm, auble tf, yealy dm. first-line management of paroxysmal supraventricular tachycardia. the american journal of emergency medicine. 1999;17(2):214-6. 22. looga r. the valsalva manoeuvre–cardiovascular effects and performance technique: a critical review. respiratory physiology & neurobiology. 2005;147(1):39-49. 23. waxman mb, wald rw, finley jp, bonet jf, downar e, sharma ad. valsalva termination of ventricular tachycardia. circulation. 1980;62(4):843-51. 24. taylor dm, wong lf. incorrect instruction in the use of the valsalva manoeuvre for paroxysmal supraventricular tachycardia is common. emergency medicine australasia. 2004;16(4):284-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e76 or i g i n a l re s e a rc h perspectives of patient handover among paramedics and emergency department members; a qualitative study majid najafi kalyani1, zheila fereidouni1, raheleh sabet sarvestani1∗, zahra hadian shirazi2, ali taghinezhad3 1. nursing department, fasa university of medical sciences, fasa, iran. 2. nursing department, shiraz university of medical sciences, fars, iran. 3. english language department, fasa university of medical sciences, fasa, iran. received: may 2017; accepted: august 2017; published online: 14 august 2017 abstract: introduction: improving patient handover is currently considered as a patient safety goal and one of the top five who priorities. so, the aim of this study was to explore the perspectives of patient handover among paramedics and emergency department staff. methods: this is a descriptive exploratory study with a qualitative content analysis approach. twenty five paramedics and emergency department staff were selected through purposeful sampling. the data were collected through semi-structured interviews in 2015 and qualitative content analysis was used to analyze the data. results: one main theme and two major categories emerged through the data analysis. in general, data analysis indicated that patient handover is a sophisticated process, which is an encounter between two separate peninsulas with different extrinsic (different environments and different equipment) and intrinsic factors (different manpower and different expectations). conclusion: designing an appropriate environment, providing adequate equipment, recruiting appropriate manpower, and clarifying the expectations are some strategies for improving patient handover conditions. keywords: allied health personnel; patient handoff; patient safety; emergency medical services; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: najafi kalyani m, fereidouni zh, sabet sarvestani r, hadian shirazi z, taghinezhad a. perspectives of patient handover among paramedics and emergency department members; a qualitative study. emergency. 2017; 5(1): e76. 1. introduction i mproving patient handover is currently considered as a patient safety goal by “the joint commission accreditation of health care” since 2006 and one of the top five world health organization (who) priorities (1). patient handover is described as sharing information, authority and answerability between individuals and teams in the health care system (2). it plays an important role in maintaining continuity of care and also a key role in teaching new students, promoting team cohesion, emotional support, socialization, maintaining social order, patient safety, and mistake detection (3, 4). the busy, overcrowded, noisy and distracting environments ∗corresponding author: raheleh sabet sarvestani; department of nursing, fasa university of medical sciences, fasa, iran. email: rahelehsabet88@gmail.com tel: 09173122634 of an emergency department (ed) coupled with time pressure, make the handover of the patient susceptible to data loss, misinformation and high rates of mistake (5). the primary phase of care in ed, including triage, resuscitation and intervention, is especially error-prone. during this timepressured period, important decisions are being made based mainly on information provided by paramedics for the ed members (2). the transfer of care between paramedics and ed members includes a handover of information, which contains demographic details, the event preceding the call, their findings, treatment and details of patient’s medical history (6). this handover is usually reported verbally, but it must be documented to provide a formal record of care for quality assurance purposes and patient safety (7). however, there is often little time to document extensive information resulting in dependence on memory when providing verbal handover. nevertheless, cultural, linguistic, and social differences between paramedics and ed members may increase the potenthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. najafi kalyani et al. 2 tial for conflict or misunderstanding (4). the most recent review on handover concluded that the quality of research on the topic is really primitive, and there are not yet enough studies to guide evidenced-based handover practices and little is known about how effectively data is transferred from paramedics to ed members who receive the patients (1, 8-10). a study by evan et al. (2010) showed that only 34% of information verbalized by paramedics was recalled by emergency nurses (11). also, a study of handover in a simulated situation showed that 18% of information transfer to other personnel was inaccurate. furthermore, there is also evidence that the documentation of information handed over by paramedics to the ed members is not completely accurate and only 67% of the information is accurate (2). since effective handover is critical to achieving the optimum management of all patients (5), communication errors are costly both for the patient and the economy (11), and transfer of care among providers has been identified as a major source of medical error (4), the present study aimed to explore the perspectives of paramedics and ed members regarding patient handover. 2. methods 2.1. study design and setting a qualitative design with inductive content analysis was used for data collection and analysis of patient handover perspectives among paramedics and ed members of valiasr hospital, fasa, during 2015. fasa is a city in fars province, iran, with a population of about 210 thousand people, having two hospitals with three urban ems units and ten road ems bases. fasa is located in a geographic place through which a transit road passes and increases the probability of road accidents. in this city, paramedics are sent on an average of 15000 missions each year, 65% of which is related to internal medicine such as heart disease and 35% are related to accidents and trauma. 2.2. ethical considerations this study was approved by the ethics committee and research council of fasa university of medical sciences. before each interview, the participants were informed about the study objectives and procedures by one of the research team members and were told that their participation was voluntary. then, they were required to sign written informed consents for taking part in the research. besides, they were reassured that they could quit the study any time they wished. confidentiality was also ensured by considering anonymity. 2.3. participants the study participants were selected through purposeful sampling. this sampling method is generally used in qualitative researches and helps select information-rich participants (12). the researchers interviewed the paramedics and ed members who had rich experience and information about this phenomenon. the inclusion criteria of the study was having at least two years of clinical experiences, and willing to participate in the study. overall, eleven nurses and fourteen paramedics were selected. 2.4. data gathering data were collected through semi-structured interviews using guide comprising probing questions in 2015 by a nurse qualified in qualitative research. the interviews were performed by one of the researchers who was experienced in qualitative researches. further supports were also provided by other team members who were experienced in emergency nursing. the interviews were audio recorded and transcribed verbatim after each session. in total, twenty-five in-depth interviews were conducted each lasting 60-90 minutes. it should be noted that the interviews were conducted in places free from distractions and at times and locations that were most suitable for the participants. prior to the interviews, the researchers established rapport with the participants. then, interviews began with general questions and moved toward more detailed inquiries depending on the participants’ responses. major interview questions were as follows: “can you describe today’s handover?”, “what is your opinion about patient handover in ed?”, “how is patient handover in your department?” and “what is it like?”. at the end of the interviews, the researchers thanked the participants for their time and asked them if there was anything they would like to add. the interviews continued until reaching data saturation point where no new information was gained. 2.5. data analysis conventional content analysis proposed by graneheim and lundman was used to analyze the data (13). after each interview, its contents were documented by the research team immediately. then, the data were read several times to gain a general understanding of the participants’ statements in line with the study objectives. after that, the research team extracted meaning units or initial codes, which were eventually merged and categorized according to similarities and differences. maxqda2 software 10.0 r250412 was used for data analysis. in the end, the final codes, including their defining properties and their relationships with each other, were reviewed in order to reach a consensus regarding the central, unifying themes emerging from the data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e76 table 1: demographic characteristics of the participants characteristic number (%) sex male 20 (80) female 5 (20) age (year) mean 18-25 7 (28) 26-30 5 (20) 31-40 10 (40) 41-50 2 (8) 51-60 1 (4) marital status married 23 (92) single 2 (8) specialty paramedic 14 (56) nurse 11 (44) job experience (years) < 5 5 (20) 5-10 15 (60) >10 y 5 (20) 2.6. rigor the procedures that were used to improve data trustworthiness were as follows: coding and categories were sent back to the participants for possible revisions. a team-based approach to analyze data was established to check the credibility. this showed a good level of agreement in interpretation and some disagreements were resolved through discussion. prolonged engagement, varied experiences, and peer checking were other strategies employed for improving the trustworthiness of the study (12-14) . 3. results 25 paramedics and ed members with the mean age of 37.2 ± 3.5 (18 60) years and mean job experience of 8.2 ± 3.8 (2 – 12) years participated in the study (80% male). the baseline characteristics of participants are listed in table 1. one main theme, two major categories and four subcategories were generated through data analysis (table 2). all in all, analysis of multiple sources of data indicated that patient handover is a sophisticated process, which is an encounter between two separate peninsulas with different extrinsic and intrinsic factors. 3.1. different extrinsic factors: 1) different environment the first subcategory emerging from data was “different environment” as one of the perspectives of paramedics and ed members regarding patient handover. almost all of the participants mentioned lack of a good environment for transferring patient information to others as a problem. they highlighted the importance of revising the architecture for improving communication during patient handover. in this regard, a paramedic said: “in my opinion, the major weakness of patient handover is space and building. emergency departments and triage are like a “crossroad”. it is very crowded and we don’t have enough concentration for reporting”. or another nurse added: “we cannot keep patient privacy during reporting. anybody can come near the patient and listen to his/her history. it is like a sidewalk here”. or another nurse said: “yesterday, the triage was very crowded. you could hear a lot of noises such as screaming, shouting, using obscene language, anything except reporting of patient handover. there were approximately ten people near a patient’s stretcher”. 2) different equipment the second category that was extracted from the data is “different equipment”. the participants strongly believed that different equipment of ambulance and ed is another challenge that increases waste of time. the following excerpt from a paramedic illustrates that different equipment is another problem. “this is my greatest pain, the equipment of our ambulance is different from that of the hospital such as stretcher, backboard or other equipment, so we should go to a storage room and search for the equipment, and this process will waste our time and lengthen our mission”. another nurse expressed a similar perception. “one of our challenges with paramedics is about equipment, our equipment in hospital is not appropriate for ambulance, so in some situations, we have to move the patient with a broken leg fixed in order to give their equipment back. this will be very dangerous for that patient”. 3.2. different intrinsic factors: 1) different manpower the third subcategory emerging from the data was “different manpower”. the participants acknowledged that recruiting appropriate manpower is very important. these participants felt that one of the challenges of patient handover is different education of manpower or lack of a qualified one. the following narrative statement described this subcategory: “we have some colleagues that have different educational backgrounds such as surgery technology or anesthesiology. they really didn’t know anything about patient handling in emergency situations, so in patient handover, they cannot transfer accurate information to others”. for example another nurse mentioned: “communication during patient handover with paramedics is hard; i think we have different experiences and languages that interfere with the clarity of speech”. also regarding this subcategory a participant stated that: “lack of qualified security and service members in this ward is another problem; they should be present during patient this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. najafi kalyani et al. 4 table 2: main category and related subcategories extracted from participant perspective main theme categories subcategories two separate peninsulas different extrinsic factors different environment different equipment different intrinsic factors different manpower different expectation handover and organize the situation”. 2) different expectations the last category that was extracted from data was “different expectations”. they mostly mentioned that during patient handover each system had different expectations from us. in this regard, a paramedic reported: “nurses asked us to transfer the patient completely and help them in some emergency situation to stabilize the patients; on the other hand, our managers want us to leave the hospital as soon as possible, in less than 10 minutes and come back to our units and become ready for the next mission”. the following statement from a paramedic shows the underpinnings of this theme: “in some situations, managing the patient in emergencies and in the ambulance is too hard, but the nurses in emergency ward expect us to transfer the patient completely during patient handover”. 4. discussion the aim of this study was to explore the perspectives of paramedics and ed members on patient handover. they believed that their handover is a sophisticated process, which is an encounter between two separate peninsulas with different extrinsic and intrinsic factors such as different environments, different equipment, different manpower, and different expectations. our results is in congruence with meisel et al. (2015) who said that patient handover between paramedics and ed members has unique challenges, because they have different clinical duties and professional culture and largely non-overlapping sites of work, leading to potential communication errors and teamwork conflicts that could be costly, especially for ill patients in the context of care (15). our study showed that patient handover did not occur in an appropriate environment. since patient handover takes place in a time-limited period and paramedics are often required to transfer sophisticated problems to multiprofessional members, this transition is highly susceptible to information loss. in this regard, mcdonagh et al. (2013) conducted a study “clinical handover at the emergency department a two way process” and found that handover can take place anywhere in the department and they recommend a specific location for patient handover (16). moreover, manser et al. (2011) highlighted that environmental factors will undermine the effectiveness of inter-professional communication across a variety of settings (17). in this regard, sabet sarvestani et al. (2015) conducted a study in pediatric department and explored the challenges of nursing handover. they found that there was not a quiet room for nursing handover, which could lead to many interruptions and decrease the quality and accuracy of handover. they recommend allocating a place far from interruptions for patient handover to improve patient data confidentiality and privacy (18). as bost et al. (2012) said ed is a chaotic and complex environment, which can result in inaccurate transfer and loss of information during handover process. the design and building quality (architecture) of an ed has principal influence on the health, safety and satisfaction of personnel and patients as well as efficiency of care. so, architectural planning and organization of ed based on the standards and allocation of a special place for handover is very important (19). on a number of occasions the nursing staff mentioned the adverse effect of a noisy ed on cognitive tasks and their ability to hear handover by paramedics. noises reduce performance of complex tasks and increase risk of error and staff burnout in the critical care setting. moreover, evans et al. (2010) suggested teaching effective listening skills to trauma team in health care systems (2). another subcategory that emerged from our data was “different equipment”. as mentioned before, having a storage to facilitate restocking of ambulances that require rapid turnover is a necessity for each standard emergency department (20). also, day et al. (2010) in their article pointed to this matter and said that it is mandatory for each hospital to have a protocol for intra-hospital transport. this protocol should address different parts of handover such as pre-transport coordination, necessary equipment, monitoring process, ways of documentation, and transport personnel/training. availability of equipment in the same size and shape in hospital is recommended to decrease paramedics’ waste of time after patient handover (21). as another aspect of our findings, different manpower was another subcategory that explained the perspective of paramedics and ed members regarding patient handover. although ambulance services play a key role in health care system, there are no good strategies for selection of these groups and little attention has been paid to their improvement. a change in the educational process is necthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e76 essary to monitor the recruitment of paramedic workforce overtime (22). also, woolard et al. (2006) said that recently the number of emergency ambulance services has increased markedly and successful development of paramedics’ role needs a shift from vocational training to educational institution (23). meisel et al. (2015) suggested some solutions for improving patient handover such as increasing ems interactions with emergency physicians and standardizing handover processes (15). however, standardization by itself is not enough. multidisciplinary training in combination with introduction of a handover tool that requires minimal information is recommended (1). the perspectives of our participants highlighted the importance of the presence of security staff during patient handover. a college for emergency medicine published a guideline for emergency department design and pointed that in all emergency departments, the proximity of security staff, preferably visible all the time, is important (20). jensen et al. (2013) said that handover is a conversation between the professionals that might improve empathy, equinity and common ground and is clearly not just an exchange of information. having different values, language and hierarchies hinder the efficacy of patient handover, they suggested a change in work-related culture from individual health professional culture to developing a common multi-professional team culture (1). in a study conducted by fairbanks et al. (2007) it was confirmed that communication errors are evident between paramedics and ed members who would ultimately take care of the patient during their ed stay (24). the last subcategory was “different expectations”. an ed is a complex workplace with a set of interdependent facilities involving many different professionals serving every single patient (7). bruce et al. (2005) found that there would be a role conflict between paramedics and ed members that can be confounding during patient handover, especially when paramedics assume more responsibility than expected (7). since the role of paramedics has recently increased in our new health care system, the rights and laws will be required to support paramedics in undertaking an extended role (23). in this regard, as it is advocated by many, including who, carter et al. (2009) and delupis et al. (2014) suggested designing an appropriate method of transmitting and receiving data and using a standardized approach to handover communication in ed (8, 25). daily activities can cause a high level of stress, especially at the time of high patient turnover. for this reason, it is imperative that clear, consistent and concise communication be undertaken to minimize the risk of incidence of adverse events. the findings of the present study challenge managers to develop new strategies that can improve patient handovers, which in turn can facilitate changes that increase the level of job satisfaction among ed members and paramedics. as a result, these can lead to a higher level of patient safety with a higher quality of care. patient handover is a skill that requires education and practice, so in this regard, in-service education is a priority and highly recommended. since improving handover practices mainly depends on the context, which is completely different in each organization due to different substructures, facilities, aims, priority and economic situation, action research is recommended to face the challenges of real-world problems. 5. limitation generalizing our findings to other clinical settings is a limitation as our study took place in one department. thus, it is recommended that further studies be conducted in other departments. furthermore, although we did twenty-five interviews, we may have missed other perspectives. despite these limitations, our findings captured a good view of the current situation for provision of a foundation to plan and implement appropriate change. 6. conclusion in general, our data analysis indicated that designing an appropriate environment, recruiting appropriate manpower, providing adequate equipment and clarifying the expectations are some strategies for improvement of patient handover between ems and ed personnel. 7. appendix 7.1. acknowledgements the authors would like to thank the research vice-chancellor of fasa university of medical sciences for approval, supervision, and funding of this research project. they also would like to appreciate the paramedics and emergency department members who participated in this study. 7.2. author contribution rss was responsible for the study conception and design. rss and zhf performed the data collection. rss and mnk1 performed data analysis. rss, zhf, zhsh and at were responsible for drafting the manuscript. rss, zhf, zhsh and at made critical revisions to the paper for important intellectual content. mnk obtained funding. rss, zhf, zhsh and at, gave administrative, technical or material support. mn and rss supervised the study. 7.3. funding/support vice-chancellor of research and technology of fasa university of medical sciences approved, supervised, and funded this research project under grant number: 94175. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. najafi kalyani et al. 6 7.4. conflict of interest none declared. references 1. jensen sm, lippert a, ostergaard d. handover of patients: a topical review of ambulance crew to emergency department handover. acta anasthesial scand 2013;57:964-70. 2. evans sm, murray a, patrick i, fitzgerald m, smith s, cameron p. clinical handover in the trauma setting: a qualitative study of paramedics and trauma team member. qual saf health care 2010:2-6. 3. thakore s, morrison w. a survey of the perceived quality of patient handover by ambulance staff in the resuscitation room. emergency medicine journal : emj. 2001;18(4):293-6. 4. horwitz li, meredith t, schuur jd, shah nr, kulkarni rg, jenq gy. dropping the baton: a qualitative analysis of failures during the transition from emergency department to inpatient care. annals of emergency medicine. 2009;53(6):701-10 e4. 5. dawson s, king l, grantham h. review article: improving the hospital clinical handover between paramedics and emergency department staff in the deteriorating patient. emergency medicine australasia : ema. 2013;25(5):393-405. 6. murray sl, crouch r, ainsworth-smith m. quality of the handover of patient care: a comparison of pre-hospital and emergency department notes. international emergency nursing. 2012;20(1):24-7. 7. bruce k, suserud bo. the handover process and triage of ambulance-borne patients: the experiences of emergency nurses. nursing critical care. 2005;10(4):201-9. 8. carter aje, davis ka, v. el, c. cd. information loss in emergency medical services handover of trauma patients prehospital emergency care 2009;13(3):280-5. 9. bost n, crilly j, wallis m, patterson e, chaboyer w. clinical handover of patients arriving by ambulance to the emergency department a literature review. international emergency nursing. 2010;18(4):210-20. 10. owen c, hemmings l, brown t. lost in translation: maximizing handover effectiveness between paramedics and receiving staff in the emergency department. emergency medicine australasia : ema. 2009;21(2):102-7. 11. evans sm, murray a, patrick i, fitzgerald m, smith s, andrianopoulos n, et al. assessing clinical handover between paramedics and the trauma team. injury. 2010;41(5):460-4. 12. speziale hs, carpenter dr. qualitative research in nursing forth ed. lippincott williams & wilkins: lippincott williams & wilkins; 2007. 13. graneheim uh, lundman b. qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. nurse education today. 2004;24(2):105-12. 14. polit df, beck ct. nursing research: generating and assessing evidence for nursing practice. 9th ed. lippincott williams & wilkins: lippincott williams & wilkins; 2008. 15. meisel zf, shea ja, peacock nj, dickinson et, paciotti b, bhatia r, et al. optimizing the patient handoff between emergency medical services and the emergency department. annals of emergency medicine. 2015;65(3):310-7. 16. mcdonagh m. clinical handover at the emergency departmenta two way process. resus conference; 27 april 2013; university of lumeric2013. 17. manser t, foster s. effective handover communication: an overview of research and improvement efforts. best practice & research clinical anaesthesiology. 2011;25(2):181-91. 18. sabet sarvestani r, moattari m, nasrabadi an, momennasab m, yektatalab s. challenges of nursing handover: a qualitative study. clinical nursing research. 2015;24(3):234-52. 19. bost n, crilly j, patterson e, chaboyer w. clinical handover of patients arriving by ambulance to a hospital emergency department: a qualitative study. internatinal emergency nursing. 2012;20(3):133-41. 20. medicine acfe. emergency department design guidelines australasian college for emergency medicine; 2014. p. 177. 21. day d. keeping patients safe during intrahospital transport. critical care nurse. 2010;30(4):18-32; quiz 3. 22. joyce cm, wainer j, piterman l, wyatt a, archer f. trends in the paramedic workforce: a profession in transition. australian health review : a publication of the australian hospital association. 2009;33(4):533-40. 23. woollard m. the role of the paramedic practitioner in the uk journal of emergency primary health care 2006;4(1):3-9. 24. fairbanks rj, bisantz am, sunm m. emergency department communication links and patterns. annals of emergency medicine. 2007;50(4):369-406. 25. delupis fdd, pisanelli p, luccio gd, kennedy m, tellini s, nensi n, et al. communication during handover in the pre-hospital/hospital interface in italy: from evaluation to implementation of multidisciplinary training through high-fidelity simulation. intern emerg med. 2014;9:57582. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e83 or i g i n a l re s e a rc h physiologic scoring systems in predicting the covid19 patients’ one-month mortality; a prognostic accuracy study farhad heydari1, majid zamani1, babak masoumi1∗, saeed majidinejad1, mohammad nasr-esfahani1, saeed abbasi2, kiana shirani3, donya sheibani tehrani4, mahsa sadeghi-aliabadi5, mohammadreza arbab6 1. department of emergency medicine, faculty of medicine, isfahan university of medical sciences, isfahan, iran. 2. anesthesiology and critical care research center, nosocomial infection research center, isfahan university of medical sciences, isfahan, iran. 3. department of infectious diseases, isfahan university of medical sciences, isfahan, iran. 4. department of it, shahid beheshti university, tehran, iran. 5. department of genetics, faculty of advanced science and technology, tehran medical sciences, islamic azad university, tehran, iran. 6. department of biology, faculty of science, yazd university, yazd, iran. received: july 2022; accepted: august 2022; published online: 19 october 2022 abstract: introduction: it is critical to quickly and easily identify severe coronavirus disease 2019 (covid-19) patients and predict their mortality. this study aimed to determine the accuracy of the physiologic scoring systems in predicting the mortality of covid-19 patients. methods: this prospective cross-sectional study was performed on covid-19 patients admitted to the emergency department (ed). the clinical characteristics of the participants were collected by the emergency physicians and the accuracy of the quick sequential failure assessment (qsofa), coronavirus clinical characterization consortium (4c) mortality, national early warning score-2 (news2), and pandemic respiratory infection emergency system triage (priest) scores for mortality prediction was evaluated. results: nine hundred and twenty-one subjects were included. of whom, 745 (80.9%) patients survived after 30 days of admission. the mean age of patients was 59.13 ± 17.52 years, and 550 (61.6%) subjects were male. non-survived patients were significantly older (66.02 ± 17.80 vs. 57.45 ± 17.07, p< 0.001) and had more comorbidities (diabetes mellitus, respiratory, cardiovascular, and cerebrovascular disease) in comparison with survived patients. for covid-19 mortality prediction, the aurocs of priest, qsofa, news2, and 4c mortality score were 0.846 (95% ci [0.821-0.868]), 0.788 (95% ci [0.760-0.814]), 0.843 (95% ci [0.818-0.866]), and 0.804 (95% ci [0.776-0.829]), respectively. all scores were good predictors of covid-19 mortality. conclusion: all studied physiologic scores were good predictors of covid-19 mortality and could be a useful screening tool for identifying high-risk patients. the news2 and priest scores predicted mortality in covid-19 patients significantly better than qsofa. keywords: covid-19; clinical decision rules; mortality; emergency service, hospital cite this article as: heydari f, zamani m, masoumi b, majidinejad s, nasr-esfahani m, abbasi s, et al. physiologic scoring systems in predicting the covid-19 patients’ one-month mortality; a prognostic accuracy study. arch acad emerg med. 2022; 10(1): e83. https://doi.org/10.22037/aaem.v10i1.1728. ∗corresponding author: babak masoumi; alzahra hospital, sofeh ave, keshvari blvd., isfahan, iran. email: bamasoumi@med.mui.ac.ir, tel: +989121979028, orcid: https://orcid.org/0000-0002-7330-5986. 1. introduction the coronavirus disease 2019 (covid-19), a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), has unfolded globally with unheardof rapidity (1). covid-19 has had a devastating impact on health care, internationally (1, 2). 6 to 20% of sufferers need to be hospitalized (2, 3). the incidence of critical disorder this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 2 amongst hospitalized patients is about 5-20%, and intensive care treatment may also be required in >25% of them (4, 5). the mortality rate amongst hospitalized subjects is estimated to be 11-28% (2, 6). therefore, it is essential to identify subjects that emerge as severely or even critically ill quickly and without problems, which can help in allocation of the limited medical and monitoring resources. using scoring systems to estimate a patient’s risk of unfavorable outcome can decrease unnecessary use of the limited available resources (1, 2, 5). several medical scoring tools have been used for risk stratification regarding sepsis and community-acquired pneumonia (cap) (2, 5). there are several valid scoring systems for predicting pneumonia mortality. the quick sequential failure assessment (qsofa) criteria were developed in 2016 (2, 5) to predict mortality in septic patients. still, recent research has recommended that qsofa is an effective tool to evaluate mortality risk in seriously ill subjects with a variety of diseases, especially in resource-constrained eventualities (7, 8). the coronavirus clinical characterization consortium (4c) mortality score was developed by the international severe acute respiratory and emerging infections consortium (isaric). it was used on adult hospitalized covid-19 patients in england, wales, and scotland to predict 30-day mortality (9, 10). in studies conducted on emergency department (ed) patients, the national early warning score (news) was the most accurate in predicting in-hospital mortality (11). in 2017, news was updated to news2 by adding new oxygen saturation (spo2) scoring scale. news2 is recommended by the royal college of physicians for use in covid-19 patients (11) and is a standardized scoring tool developed to improve the detection of deterioration in acutely ill patients (12). news2 has shown good ability in prediction of adverse outcomes in patients attending the ed with suspected covid-19. in 2021, pandemic respiratory infection emergency system triage (priest) tool was developed and validated among adult patients with suspected covid-19 in ed to address any pandemic respiratory infection, including covid-19. it was created by adding age, sex, and performance status to news2 (13). the present study was performed at the time of the circulation of the delta variant. previous studies have suggested that physiologic scoring systems are practical tools to assess mortality risk in critically ill patients (9-14). therefore, these scores can assist emergency physicians in predicting the mortality of covid-19 hospitalized patients. this study was conducted to estimate and compare the accuracy of the qsofa, 4c mortality, news2, and priest scores in predicting the mortality of covid-19 patients in the emergency department setting. 2. methods 2.1. study setting and design this prospective cross-sectional study was conducted at al-zahra hospital (a university-affiliated, covid-19 referral hospital) in isfahan, iran, between june 22, 2021, and november 21, 2021 (at the time of circulation of the delta variant of the coronavirus). the clinical characteristics of the participants were collected by the emergency physicians and the accuracy of the quick sequential failure assessment (qsofa), coronavirus clinical characterization consortium (4c) mortality, national early warning score-2 (news2), and pandemic respiratory infection emergency system triage (priest) scores in prediction of one-month mortality was evaluated. this study was approved by the ethics committee of isfahan university of medical sciences (code: ir.mui.med.rec.1399.932), and the study participants signed the informed consent. 2.2. participants adult subjects (over 18 years of age) with confirmed covid19 infection, who were admitted to the emergency department (ed) of al-zahra hospital were eligible for study participation. covid-19 infection was established according to the who interim guidance (15). pregnant patients, those who disagreed to participate in the study, those hospitalized for other medical conditions unrelated to covid-19, and patients transferred from other hospitals were excluded. 2.3. data collection the emergency medicine residents evaluated and managed the patients in the ed based on the standard protocol at al-zahra hospital. the patients’ demographic information (gender and age), baseline variables, and clinical and laboratory data were collected on ed admission. clinical data including signs and symptoms, blood pressure (bp), respiratory rate (rr), heart rate (hr), avpu (’alert’, ’voice’, ’pain’, ’unresponsive’), temperature, o2 saturation (spo2), laboratory findings, and triage level based on emergency severity index (esi) version 4, and chest computed tomography (ct) scans were recorded. these data were extracted to calculate the qsofa, 4c mortality, news2, and priest scores. the primary outcome was mortality within 30 days after admission to the ed. the qsofa consists of three parameters. one point is allotted to each variable: sbp ≤100 mm hg, rr ≥22 breaths/minute, and altered mental status (gcs<15). the score ranges from 0 to 3 (7). the news2 tool comprises six physiological variables (rr, spo2, sbp, hr, level of consciousness or new confusion, and temperature). each variable is scored from 0 to 3. finally, two this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e83 points are added for patients requiring supplementary oxygen treatment (11) (appendix 1). the news-2 assessment categorizes patients into low risk (0–4), medium risk (5–6), and high risk (≥7). the priest score can be calculated by adding age and gender, and performance status to the parameters of the news2 score (appendix 1). the score ranges from zero to 29 points (13). the 4c mortality score includes eight variables (age, sex, number of comorbidities, rr, spo2, gcs, bun level, and creactive protein level) (appendix 2). the total score ranges between 0 and 21 points (9). 2.4. statistical analysis based on similar studies (2), assuming specificity of 80%, the mortality rate of 20%, the estimation accuracy of 95%, and type-1 error of 3%, the minimum required sample size was 853 people. spss software version 25.0 (ibm, armonk, ny) was applied to analyze the variables. categorical data were described as frequency (%), and continuous data were expressed as mean and standard deviation (sd) or 95% confidence interval (ci). chi-square test and student’s t-test, or the mann-whitney u test were performed to compare variables. the area under a receiver operating characteristic (auroc) curve was calculated to evaluate and compare the effectiveness of the qsofa, 4c mortality, news2, and priest scores in predicting mortality. p-value less than 0.05 in twotailed tests was considered significant. 3. results 3.1. patients’ baseline characteristics nine hundred and twenty-one subjects were included in this study. of them, 745 (80.9%) patients had survived 30 days after admission. the mean age of patients was 59.13 ± 17.52 years, and 550 (61.6%) subjects were male. the mean length of hospital stay was 8.69 ± 8.91 days. the most common underlying diseases were hypertension (32.6%) and diabetes (32.2%). the most common symptoms on admission were dyspnea (72.6%) and fever (65.1%). the baseline characteristics and laboratory parameters of survived and non-survived patients are compared in table 1 and 2. non-survived patients were significantly older (66.02 ± 17.80 vs. 57.45 ± 17.07, p< 0.001) and had more comorbidities (diabetes mellitus, respiratory, cardiovascular, and cerebrovascular disease) in comparison with survived patients. among vital parameters on ed admission, spo2, rr and hr significantly differed between survived and non-survived patients. there were significant differences between survivor and non-survivor patients regarding gcs, length of hospital stay, qsofa, priest, news2, and 4c mortality scores. the lymphocyte counts and hemoglobin in non-survived pafigure 1: area under the receiver operating characteristic curve of different scoring systems in predicting the 30-day mortality of covid-19 patients. tients were significantly lower than survived patients (p < 0.001). the d-dimer, blood sugar, and lactate dehydrogenase levels in non-survived patients were significantly higher than those who survived. 3.2. comparing the accuracy of scoring systems roc curves were drawn to calculate the sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), and cut-off values of scores to predict covid19 mortality. the optimal cut-off values of ≥2 for the qsofa, ≥8 for priest, ≥6 for news2, and ≥13 for the 4c mortality score were established. the npv of the priest, qsofa, news2, and 4c mortality scores for mortality were 96.0%, 95.2%, 94.0%, and 91.5%, respectively (table 3). for covid-19 mortality prediction, the aurocs of priest, qsofa, news2, and 4c mortality score were 0.846 (95% ci [0.821-0.868]), 0.788 (95% ci [0.760-0.814]), 0.843 (95% ci [0.818-0.866]), and 0.804 (95% ci [0.776-0.829]), respectively. all scores were good predictors of covid-19 mortality (figure 1). the auroc analysis showed that the news2 and priest scores were more successful than qsofa (p=0.004 and p=0.001) in predicting mortality for covid-19 patients (table 4). 4. discussion due to the limitations of medical resources during the covid-19 outbreak, it is essential to initially assess covid19 patients in terms of disease severity to ensure primary medical management and interventions. therefore, one of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 4 table 1: comparison of demographic and clinical characteristics of covid-19 patients based on 30-day mortality characteristics total (n=921) survived (n=745) non-survived (n=176) p age (year) 59.13 ± 17.52 57.45 ± 17.07 66.02 ± 17.80 0.001 gender male 550 (61.6) 436 (58.5) 114 (64.8) 0.128 female 371 (38.4) 309 (41.5) 62 (35.2) comorbidities respiratory disease 127 (13.8) 82 (11.0) 45 (25.6) <0.001 cardiovascular disease 164 (17.8) 122 (16.4) 42 (23.9) 0.032 diabetes mellitus 294 (32.2) 219 (29.8) 75 (42.6) 0.001 hypertension 300 (32.6) 236 (31.7) 64 (36.4) 0.357 cerebrovascular disease 84 (9.1) 54 (7.2) 30 (17.0) 0.001 chronic kidney disease 98 (10.6) 77 (10.3) 21 (11.9) 0.413 chronic liver disease 27 (2.9) 21 (2.8) 6 (3.4) 0.452 malignancy 76 (8.3) 55 (7.4) 21 (11.9) 0.053 signs and symptoms fever 600 (65.1) 499 (67.0) 101 (57.4) 0.041 cough 549 (59.6) 448 (60.1) 101 (57.4) 0.537 dyspnea 669 (72.6) 542 (72.8) 127 (72.2) 0.874 fatigue 497 (54.0) 412 (55.3) 85 (48.3) 0.093 sore throat 84 (9.12) 67 (8.99) 17 (9.66) 0.388 myalgia 208 (22.6) 178 (23.9) 30 (17.0) 0.051 diarrhea 215 (23.3) 188 (25.2) 27 (15.3) 0.005 opioid yes 91 (9.9) 70 (9.4) 21 (11.9) 0.593 glasgow coma scale mean ± sd 11.61± 2.03 12.32 ± 6.92 10.02 ± 2.67 <0.001 length of stay (day) mean ± sd 8.68± 8.91 8.06 ± 7.39 11.23 ±13.26 0.003 vital parameters hr; bpm 88.04±12.41 87.25±11.91 91.31±13.92 0.043 sbp; mmhg 23.53±17.64 23.95±17.87 21.81±16.71 0.463 dbp; mmhg 75.71± 11.56 75.84±11.71 75.19±11.04 0.864 rr; bpm 20.59±3.09 20.31±2.88 21.76±3.65 0.001 temp; °c 37.34 ± 0.61 37.33±0.63 37.37±0.51 0.312 spo2;% 88.99± 6.06 91.40±6.03 80.31±5.95 0.001 scores qsofa 1.46± 0.61 1.33±0.53 2.04±0.57 <0.001 priest 7.15±2.92 6.61±2.72 9.42±2.66 <0.001 4c mortality 10.42±3.70 9.67±3.52 13.58±2.63 <0.001 news2 4.81±2.70 4.17±2.34 7.54±2.40 <0.001 data are presented as mean ± standard deviation (sd) or frequency (%). hr: heart rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; rr: respiratory rate; temp: temperature; spo2: oxygen saturation. the most critical tasks of emergency physicians is rapid and accurate screening of subjects at risk of death in severe or critically ill covid-19 patients to provide them with additional monitoring, intervention, or intensive care (16). in such situations, scoring systems can help overcome limitations. each scoring tool has its advantages and disadvantages. the 30-day mortality in the current study was high (19.1%). it was in line with previous studies (ranging from 19.2% to 20.9%) (2, 6, 10). consistent with the current study, previous studies have shown that non-survived covid-19 patients were significantly older, had a higher respiratory rate, a lower spo2 on ed arrival, and had more underlying diseases than those who survived (2, 5, 8, 11). most patients presented with respiratory tract symptoms such as dyspnea and cough, fever, and fatigue. previous studies reported that the most common symptoms include cough (60–86%), dyspnea (53–80%), and taste or smell disturbance (64–80%) (10, 17-19). these results are similar to the present study. the current study has compared the performance of four different scoring systems in predicting covid-19 mortality. the news2 and priest, with auroc of 0.843 and 0.846 in predicting mortality of covid-19 patients, are significantly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e83 table 2: comparing the laboratory parameters of the covid-19 patients at the time of admission between survived and non-survived characteristics total (n=921) survived (n=745) non-survived (n=176) p white blood cells, ×109 /ml 7.096± 4.279 6.964 ± 4.089 7.656±5.010 0.125 lymphocytes, ×109 /ml 1.59±0.91 1.71 ± 0.88 1.09 ± 0.87 <0.001 hemoglobin, g/l 13.41±2.13 13.03 ±1.86 15.00 ± 2.46 <0.001 platelets, ×109 /ml 182.6 ±81.8 183.2±82.5 179.8±79.5 0.721 pao 2, mmhg 45.60±23.03 46.60±23.70 41.48±19.72 0.012 ph 7.32±0.10 7.31 ±0.09 7.37±0.10 <0.001 paco2 41.50±12.10 41.72±11.69 40.61±13.71 0.260 hco3 21.29±4.85 21.29±4.79 21.27±5.12 0.803 alt, u/l 44.45±27.31 45.20 ±27.17 41.33 ±27.91 0.352 ast, u/l 55.16±23.38 54.26±22.97 58.79±24.81 0.185 bun, mmol/l 20.13±12.69 19.74±12.38 21.79±13.95 0.476 creatinine, umol/l 1.59±1.44 1.59±1.17 1.61±0.98 0.973 potassium, mmol/l 4.68±1.23 4.69±1.32 4.64±0.79 0.985 sodium, mmol/l 137.14±7.86 137.26±8.35 136.65±5.47 0.130 ferritin, 528.1±380.2 519.3±391.0 579.5±311.8 0.235 d-dimer 910.5±841.0 881.5±851.7 1018.6±798.2 <0.001 blood sugar 130.28±57.26 127.59±59.71 141.50±44.38 <0.001 creatine kinase 308.1±411.3 303.9±405.6 326.9±440.1 0.929 lactate dehydrogenase 672.6±310.0 646.5±280.4 776.9±393.3 0.019 c-reactive protein 68.15±44.11 67.88±44.85 69.28±41.23 0.880 esr 48.87±25.94 49.20±25.56 47.54±23.41 0.696 data are presented as mean ± standard deviation (sd). alt: alanine aminotransferase; ast: aspartate aminotransferase; bun: blood urea nitrogen; esr: erythrocyte sedimentation rate. table 3: screening performance characteristics of physiologic scoring systems in predicting the 30-day mortality of covid-19 patients variables 4c mortality news2 qsofa priest cut-off ≥13 ≥6 ≥2 ≥8 sensitivity 68.75 (61.3 75.5) 78.98 (72.2 – 84.7) 85.80 (79.7 -90.6) 87.50 (81.7 – 92.0) specificity 79.19 (76.1 – 82.1) 77.76 (74.6 -80.7) 66.87 (63.3 – 70.2) 71.05 (67.6 – 74.3) ppv 43.8 (39.7 48.1) 45.7 (41.9 – 49.6) 37.9 (35.2 – 40.8) 41.6 (38.6 – 44.7) npv 91.5 (89.6 – 93.1) 94.0 (92.1 – 95.4) 95.2 (93.2 – 96.6) 96.0 (94.2– 97.3) plr 3.30 (2.78 3.92) 3.55 (3.04 – 4.15) 2.59 (2.30 – 2.91) 3.02 (2.67 – 3.43) nlr 0.39 (0.32 0.49) 0.27 (0.20 0.36) 0.21 (0.15 0.31) 0.18 0.12 0.26) auc 0.804 (0.776-0.829) 0.843 (0.818-0.866) 0.788 (0.760-0.814) 0.846 (0.821-0.868) data are presented with 95% confidence intervals. ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio; and auc: area under the receiver operating characteristic curve. table 4: comparison of the area under the receiver operating characteristic curve of different scoring systems in predicting the 30-day mortality of covid-19 patients qsofa priest 4c news2 qsofa – 0.001 0.357 0.004 priest – 0.021 0.870 4c – 0.073 news2 – superior to qsofa (auroc = 0.778). priest score did not perform significantly better than the news2 score. covino et al. demonstrated that news2 predicted death within 48 hours from ed admission with auroc of 0.753 [95% ci 0.703 -0.798], with 72.7% [95% ci 39.0 94.0] sensitivity and 72.7% [95% ci 67.6 77.5] specificity (11). in another study, news2 demonstrated an auroc of 0.78 for in-hospital mortality (4). previous studies reported that news-2 had an excellent performance (auc = 0.842–0.894) (13, 20, 21). they showed that news-2 was the best tool for evaluating the prognosis of covid-19 patients compared to several other tools (12, 20). these findings were in line with the present study. news2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 6 can be used as a triage tool to predict the mortality of covid19 patients and allocate the limited resources. the diagnostic ability of qsofa for the prediction of hospital mortality in the current study (auroc=0.788) was comparable to liu et al. (auroc=0.742), wilfong et al. (auroc=0.801), and jang et al. (auroc=0.779) in covid-19 patients (16, 22, 23). these findings showed that qsofa is quite a good tool for predicting hospital mortality in covid-19 patients. the priest study examined 20891 suspected covid-19 patients in 70 emergency departments. triage scores provided good but not excellent discrimination with good sensitivity at the expense of specificity in patients with suspected covid19 (24). this study did not suggest any cut-off point to apply for decision-making in covid-19 patients. goodacre et al. demonstrated that priest scores ≥5 predicted 30-day mortality with 98% sensitivity (13). marincowitz et al. reported that the news2 and priest scores achieved high estimated sensitivities concerning 30-day mortality (14). in the present study, the additional components of the priest score improved sensitivity and npv. the 4c mortality score has been validated in over 57,000 patients in previous studies in several settings (4, 9, 10, 25, 26). the auroc of the 4c mortality score in the present study (0.804 [95% ci, 0.776-0.829]) is consistent with the results of previous studies in other countries. the auroc of the 4c mortality score was 0.84 (95% ci, 0.79-0.88) in a dutch population (25), 0.78 (95% ci, 0.75-0.81) in a brazilian and spanish population (26), and 0.85 (95% ci, 0.79-0.89) in a united states population (27). citu et al. showed that the news with an auroc of 0.861 predicted mortality in covid-19 patients and was significantly superior to the 4c mortality score (auroc = 0.818) (28). ocho et al. demonstrated that for mortality prediction, auroc of the 4c mortality score (0.84 [95% ci, 0.76–0.92]) was higher than qsofa (0.66 [95% ci, 0.53–0.78]) (29). these results were similar to the present study. therefore, the 4c mortality score is a useful tool to assess mortality risk in covid-19 patients. the npv of the priest, qsofa, news2, and 4c mortality scores for in-hospital mortality were 96.0%, 95.2%, 94.0%, and 91.5%, respectively. the high npv acts as a gatekeeper accurately identifying low-risk patients. the priest had the highest sensitivity and npv for mortality prediction. thus, it is particularly well in identifying covid-19 patients who were at low risk of death. for triaging patients in the ed, it is important to have a high npv for predicting severe covid-19 to avoid inappropriately admitting patients at risk of deterioration to a non-critical care area. the priest, qsofa, and news2 scores are calculated without laboratory tests or diagnostic imaging, while the 4c mortality score needs laboratory tests. therefore, the 4c mortality score is more time-consuming than others. the priest, qsofa, and news2 scores can predict patient deterioration quickly and simply in covid-19 patients who need immediate treatment to minimize mortality in covid-19 patients. although a single evaluation on hospital admission has limited predictive ability, these scores could be a helpful screening tool to evaluate covid-19 patients at the time of ed arrival. however, these should only supplement and not replace clinical judgment. due to silent hypoxemia in severe covid-19, the accuracy of the qsofa score in predicting hospital mortality decreases. these patients appear to breathe comfortably even at low spo2. this score only counts the respiratory rate and does not consider spo2. therefore, it has limitations in predicting mortality in covid-19 patients. an advantage of other scores compared to the qsofa is that both hypoxemia and respiratory rate are included as scoring parameters. 5. limitations our study has some limitations. a convenience sampling method was used, and the researcher was present in the ed, which may have caused selection bias. this study was a single-center study with limited generalizability, and the findings may not apply to other environments with different populations or healthcare systems. additionally, the value of a single evaluation is limited, and patients admitted to the hospital should be reassessed frequently for signs of deterioration. 6. conclusion all studied physiologic scores were good predictors of covid-19 mortality and these can be considered a useful screening tool to identify the high-risk patients. the news2 and priest scores predicted mortality in covid-19 patients significantly better than qsofa. 7. declarations 7.1. acknowledgments we would like to express our sincere gratitude towards the personnel of the emergency departments of alzahra hospital, isfahan, iran. 7.2. authors’ contributions all authors; contributed to conception, study design, and data collection and evaluation. f.h. and m.z.; contributed to statistical analysis and interpretation of data. f.h. and m.z.; drafted the manuscript, which was revised by s.a., k.s., and s.m. all authors read and approved the final manuscript. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e83 7.3. availability of data and materials the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. 7.4. ethics approval and consent to participate this study was approved by the ethics committee of isfahan university of medical sciences (code: ir.mui.med.rec.1399.932), and the study participants signed the informed consent. 7.5. funding this study was financially supported by isfahan university of medical sciences. 7.6. competing interests the authors declare no conflict of interest. references 1. azizkhani r, heydari f, sadeghi a, ahmadi o, meibody aa. professional quality of life and emotional well-being among healthcare workers during the covid-19 pandemic in iran. front emerg med. 2022;6(1):e2. 2. artero a, madrazo m, fernández-garcés m, muiño miguez a, gonzález garcía a, crestelo vieitez a, et al. severity scores in covid-19 pneumonia: a multicenter, 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using early warning scores. resuscitation. 2020;156:84-91. 12. myrstad m, ihle-hansen h, tveita aa, andersen el, nygård s, tveit a, et al. national early warning score 2 (news2) on admission predicts severe disease and inhospital mortality from covid-19–a prospective cohort study. scand j trauma resusc emerg med. 2020;28(1):18. 13. goodacre s, thomas b, sutton l, burnsall m, lee e, bradburn m, et al. derivation and validation of a clinical severity score for acutely ill adults with suspected covid-19: the priest observational cohort study. plos one. 2021;16(1):e0245840. 14. marincowitz c, sutton l, stone t, pilbery r, campbell r, thomas b, et al. prognostic accuracy of triage tools for adults with suspected covid-19 in a prehospital setting: an observational cohort study. emerg med j. 2022;39(4):317-24. 15. organization wh. public health surveillance for covid19: interim guidance, 16 december 2020. world health organization; 2020. 16. liu s, yao n, qiu y, he c. predictive performance 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et al. prognostic accuracy of emergency department triage tools for adults with suspected covid19: the priest observational cohort study. emerg med j 2021;38(8):587-93. 25. van dam pm, zelis n, van kuijk sm, linkens ae, brüggemann ra, spaetgens b, et al. performance of prediction models for short-term outcome in covid-19 patients in the emergency department: a retrospective study. ann med. 2021;53(1):402-9. 26. neto fl, marino lo, torres a, cilloniz c, marchini jfm, de alencar jcg, et al. community-acquired pneumonia severity assessment tools in patients hospitalized with covid-19: a validation and clinical applicability study. clin microbiol infect. 2021;27(7):1037. e1-. e8. 27. riley jm, moeller pj, crawford ag, schaefer jw, cheneypeters dr, venkataraman cm, et al. external validation of the covid-19 4c mortality score in an urban united states cohort. am j med sci. 2022;364(4):409-13. 28. citu c, gorun f, motoc a, ratiu a, gorun om, burlea b, et al. evaluation and comparison of the predictive value of 4c mortality score, news, and curb-65 in poor outcomes in covid-19 patients: a retrospective study from a single center in romania. diagnostics. 2022;12(3):703. 29. ocho k, hagiya h, hasegawa k, fujita k, otsuka f. clinical utility of 4c mortality scores among japanese covid-19 patients: a multicenter study. j clin med. 2022;11(3):821. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e83 appendix 1: national early warning score-2 (news2) and pandemic respiratory infection emergency system triage (priest) variable categories points ≤8 3 9–11 1 respiratory rate, breaths per minute 12–20 0 21–24 2 ≥25 3 ≤91% 3 spo2 (on room air or supplemental) 92–93% 2 94–95% 1 ≥96% 0 oxygen supplemental oxygen 2 room air 0 ≤35.0 °c 3 35.1–36.0 °c 1 temperature 36.1–38.0 °c 0 38.1–39.0 °c 1 ≥39.1 °c 2 ≤90 3 91–100 2 systolic blood pressure, mm hg 101–110 1 111–219 0 ≥220 3 ≤40 3 41–50 1 pulse rate, beats per minute 51–90 0 91–110 1 111–130 2 ≥131 3 consciousness alert 0 confused or not alert 3 16–49 0 age in years* 50–65 2 66–80 3 >80 4 sex* female 0 male 1 unrestricted normal activity 0 limited strenuous activity, can do light activity 1 performance status* limited activity, can self-care 2 limited self-care 3 bed/chair bound, no self-care 4 *it is only used in the priest score. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. heydari et al. 10 appendix 2: coronavirus clinical characterization consortium (4c) mortality score variable points < 50 0 50–59 2 age in years 60–69 4 70–79 6 ≥80 7 sex at birth female 0 male 1 0 0 number of comorbidities 1 1 ≥2 2 <20 0 respiratory rate (/minute) 20–29 1 ≥30 2 peripheral oxygen saturation on room air ≥92% 0 <92% 2 glasgow coma scale 15 0 <15 2 urea <7 mmol/l or bun <19.6 mg/dl 0 urea/ blood urea nitrogen urea 7–14 mmol/l or bun 19.6–39.2 mg/dl 1 urea >140 mmol/l or bun >39.2 mg/dl 3 < 50 mg/l 0 c-reactive protein 50–99 mg/l 1 ≥100 mg/l 2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 45 emergency (2016); 4 (1): 45-46 photo quiz a 52-year-old woman with a palpable abdominal mass yuh-jeng yang1, chin-chu wu2, tzong-luen wang1,3, aming chor-ming lin1,3,4* 1. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. department of diagnostic radiology, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. school of medicine, fu-jen catholic university, new taipei city, taiwan. 4. department of intensive care unit, shin kong wu ho-su memorial hospital, taipei, taiwan *corresponding author: aming chor-ming lin; emergency department, shin kong wu ho-su memorial hospital, 95 wen chang rd, taipei, taiwan. tel: 886-02-28332211 ext 2082; fax: 886-02-28353547; e-mail: amingphd@yahoo.com.tw received: jun 2015; accepted: august 2015 case presentation: 52-year-old woman was presented to the emergency department with complaint of unspecific abdominal pain and a 2-week hypermenorrhea. the patient did not have nausea, vomiting, fever, or any other symptoms. she had a history of diabetes mellitus for which she was under medical treatment, and a surgical history of a cesarean section 20 years ago. on arrival, she was vitally stable. her blood pressure was 120/68 mmhg, with a heart rate of 82 beats/minute and a respiratory rate of 20 breaths/minute. she was afebrile. her abdominal examination revealed a lower segment cesarean section scar, lower abdominal fullness and a round mobile palpable mass in right lower quadrant. bowel sounds were normal. physical examination of all other parts did not show any positive findings. complete blood cell count and biochemistry profiles were requested and all were reported in normal range. carcinoembryonic antigen (cea) as well as alpha-fetoprotein were also normal. the patient underwent abdominopelvic computed tomography (ct), the results of which are shown in figure 1 and figure 2. what is your diagnosis? a figure 1: axial view of patient’s abdominopelvic computed tomography. figure 2: coronal view of patient’s abdominopelvic computed tomography. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yuh-feng et al 46 diagnosis: abdominopelvic ct revealed an 8×7×6 cm round welldefined soft tissue mass containing cystic and solid components in the lower right abdominal area, suggesting a gynecologic tumor. a surgical resection of the tumor was performed, and the macroscopic pathological study revealed a gossypiboma inside the mass with a foreign body reaction. case fate: with concern of right ovarian carcinoma, she underwent an exploratory laparotomy. an encapsulated sponge surrounded by omentum was removed. the patient had an uneventful postoperative recovery and was discharged two days later. discussion: retained surgical sponge or gossypiboma, is an infrequent but serious surgical complication that may lead to significant medicolegal problems (1, 2). the incidence of retained foreign bodies following surgery has a reported rate of 0.06% to 0.1%. however, as gossypiboma is asymptomatic in many patients, its incidence is often underestimated (3). gossypibomas are most frequently discovered in the abdomen but also reported in other parts of the body (4). it can be a challenging diagnosis due to the wide range of presentations. the clinical presentations vary and depend on location and size of the foreign body. inflammatory body reaction, including exudative and aseptic fibrous, can also affect its manifestations (3, 5). in our case, the natural evolution of a retained sponge caused a foreign body reaction to form a foreign granuloma that mimicked a soft tissue neoplasm. gossypiboma in the abdomen can be misdiagnosed as mass or cyst (5). the clinical presentation may present as acute or chronic abdominal pain, abscess formation, fistula formation, perforation, intestinal obstruction or bleeding (6). diagnosis of the gossypiboma can be made by various imaging methods such as x-ray, ultrasonography (us), ct, magnetic resonance imaging (mri) or fluorodeoxyglucose positron emission tomography (fdg-pet) (3, 7, 8). however, generally ct is recommended as the best option for this purpose in suspected cases. the ct radiographic features of abdominal gossypibomas include low-density mass with a thin enhancing capsule and spongiform appearance with gas bubbles (9, 10). operative removal of the foreign body must almost always be performed along with treating its complications. there are some case reports for other options such as colonoscopy (11-13). conclusion: a high index of suspicion is needed to diagnose gossypiboma. retained foreign body should be in the differential diagnosis of patients with a history of previous operation. acknowledgments: we acknowledge all staff of emergency department of shin kong wu ho-su memorial hospital, taipei, taiwan. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. silva sm, sousa jbd. gossypiboma after abdominal surgery is a challenging clinical problem and a serious medicolegal issue. abcd arquivos brasileiros de cirurgia digestiva (são paulo). 2013;26(2):140-3. 2. rajagopal a, martin j. gossypiboma—“a surgeon’s legacy”. diseases of the colon & rectum. 2002;45(1):119-20. 3. rappaport w, haynes k. the retained surgical sponge following intra-abdominal surgery: a continuing problem. archives of surgery. 1990;125(3):405-7. 4. mavioglu l, ertan c, mungan u, ozatik ma. paracardiac gossypiboma (textiloma) in 2 patients. texas heart institute journal. 2015;42(3):259-61. 5. rajput a, loud pa, gibbs jf, kraybill wg. diagnostic challenges in patients with tumors case 1. gossypiboma (foreign body) manifesting 30 years after laparotomy. journal of clinical oncology. 2003;21(19):3700-1. 6. karaoglan m, ipekci f, sert i, ozturk s, sahin ag. massive upper and lower gastrointestinal bleeding due to intraabdominal gossypiboma. elective medicine journal. 2015;2(4):426-7. 7. gümüs m, gümüs h, kapan m, önder a, tekbas g, baç b. a serious medicolegal problem after surgery: gossypiboma. the american journal of forensic medicine and pathology. 2012;33(1):54-7. 8. yuh-feng t, chin-chu w, cheng-tau s, min-tsung t. fdg pet ct features of an intraabdominal gossypiboma. clinical nuclear medicine. 2005;30(8):561-3. 9. o'connor ar, coakley fv, meng mv, eberhardt s. imaging of retained surgical sponges in the abdomen and pelvis. american journal of roentgenology. 2003;180(2):481-9. 10. manzella a, filho pb, albuquerque e, farias f, kaercher j. imaging of gossypibomas: pictorial review. american journal of roentgenology. 2009;193(6_supplement):s94-s101. 11. lauwers pr, van hee rh. intraperitoneal gossypibomas: the need to count sponges. world journal of surgery. 2000;24(5):521-7. 12. hinrichs c, methratta s, ybasco ac. gossypiboma treated by colonoscopy. pediatric radiology. 2003;33(4):261-2. 13. yildirim s, tarim a, nursal tz, et al. retained surgical sponge (gossypiboma) after intraabdominal or retroperitoneal surgery: 14 cases treated at a single center. langenbeck's archives of surgery. 2006;391(4):390-5. archives of academic emergency medicine. 2022; 10(1): e77 or i g i n a l re s e a rc h game-based vs. case-based training for increasing knowledge and behavioral fluency of nurse students regarding crisis and disaster management; a quasiexperimental study mohsen masoumian hosseini1, toktam masoumian hosseini2∗, karim qayumi3, najibullah baeradeh4 1. department of e-learning in medical education, smart university of medical sciences, tehran, iran. 2. department of nursing, school of nursing and midwifery, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 3. centre of excellence for simulation education and innovation, department of surgery, university of british columbia, vancouver, bc, canada. 4. student research committee, department of epidemiology, school of health, shiraz university of medical sciences, shiraz, iran. received: july 2022; accepted: august 2022; published online: 24 september 2022 abstract: introduction: nurses play an active role in disaster response, and the ability of nurses to appropriately apply management principles during large-scale disasters or mass casualty incidents is of critical importance. this study aimed to compare the effect of game-based training (gbt) and case-based training (cbt) on nursing students’ knowledge and behavioral fluency regarding crisis and disaster management. methods: this is a quasi-experimental study with a pretest-posttest design. convenience sampling was used to select third-year nursing students who had completed their clinical clerkship at the time of the study (n=60). in the intervention group, disaster-themed games were used, while in the control group, cbt was used. the emergency and crisis management course consisted of this study’s theoretical and clinical training phases. after completion of the theoretical phase (five weeks), the practical part (four weeks) is completed as an internship. the data was collected from the disaster nurses’ knowledge questionnaire, demographic survey, and measurement checklists for disasters and crises at five stations. results: gbt students achieved significantly higher knowledge scores than cbt students after training (p < 0.001). cbt and gbt groups had no significant differences in objective structured clinical examination (osce)1 pretest scores. posttest1-osce2 and posttest2-osce3 scores showed significant differences after one week (p < 0.001) and one month (p < 0.001). the difference in mean pretest and posttest1 scores was statistically significant in both groups. a comparison of posttest scores between one month after gbt training (69.03 ± 6.09) and one week after it (69.23 ± 6.14) revealed no statistical significance (p = 0.056). conclusion: nursing students’ knowledge and behavioral fluency regarding crisis management were more effectively improved by using the disaster and crisis game than by using a case-based method. keywords: education; games, experimental ; knowledge; disaster medicine; teaching cite this article as: masoumian hosseini m, masoumian hosseini t, qayumi k, baeradeh n. game-based vs. case-based training for increasing knowledge and behavioral fluency of nurse students regarding crisis and disaster management; a quasi-experimental study. arch acad emerg med. 2022; 10(1): e77. https://doi.org/10.22037/aaem.v10i1.1739. ∗corresponding author: toktam masoumian hosseini; department of nursing, school of nursing and midwifery, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. email: masoumiant99@gamil.com, tel: 09158279655, orcid: https://orcid.org/0000-0003-3093-8799. 1. introduction since nurses are the largest health care workforce, they play a critical role in disaster response. therefore, every nurse must be able to respond to disasters actively and navigate disaster care (1). fluent behavior is defined as accuracy coupled with speed, which is essential for decision-making during a disaster (2). there are three characteristics of fluent behavior. these are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masoumian hosseini et al. 2 durability (consistency over time), stability (i.e., maintaining the behavior in a distracting environment), and generalizability (generalizing to a new situation) (3, 4). it is challenging to improve students’ ability to cope with disasters by applying knowledge alone because disasters are situational (5). the discrepancy between knowledge and practice in disaster nursing education is a significant problem (6), and traditional teaching methods do not prepare nursing students to deal with mass casualty incidents (7). meanwhile, a precision teaching framework ensures that learner performance is monitored to determine when fluency has been achieved (3). in the words of kunzelmann (1970), "precision teaching is not a method. it is a way of teaching" (8). interventions that involve precision teaching typically include the following steps: 1) establishing a fluency criterion (a period during which an expert can comfortably and accurately perform the task); 2) frequency building, which involves the learner repeatedly performing the behavior and receiving feedback on it (timed learning trials); 3) using the standard celeration chart (a semi-logarithmic chart illustrating the frequency of a target behavior) to monitor progress, which illustrates whether learning gains are occurring or whether teaching tactics should be changed (3, 8). students in nursing education have few experiences with disasters, and their imaginations are limited (9). technology development in the last decade has influenced how students learn by changing their learning and behavior patterns (10). combining interactive scenarios and animated speakers can be a powerful teaching tool for disaster nursing education by combining treatment situations with technology (11). lydon et al. (2017) reported that medical students who received simulation-based training with precision teaching to practice venipuncture performed better than their untrained peers and hospital doctors. learning was transferable to the clinical setting, and performance was maintained during distraction and follow-up (4). game-based instruction is believed to increase students’ motivation to learn and thus promote acquiring knowledge and skills (12). in recent years, a growing body of literature has been published on the potential of games as a tool to enhance nursing education (13). however, previous research has mainly focused on students’ learning experiences with games (14). this study aims to compare the effect of gbt with precision teaching and cbt on nursing students’ knowledge and behavioral fluency regarding crisis and disaster management. 2. methods 2.1. study design and setting this quasi-experimental study, with a pretest-posttest design, examined how gbt with precision teaching improved disaster nursing management knowledge & behavioural fluency in nursing students of torbat heydarieh university of medical sciences between 2021 and 2022. emergency and crisis management is one of the courses in the three-year bachelor of science in nursing (bsn) degree program. the curriculum consists of 34 hours spread over nine weeks. the emergency and crisis management course consisted of this study’s theoretical and clinical training phases. after completion of the theoretical phase (five weeks), the practical part (four weeks) is completed in the form of an internship. the flow diagram and phases of the study are shown in figure 1. ethical approval for the research was obtained from the smart university of medical sciences research ethics committee (ethics code: ir.vums.rec.1400.028). informed consent was obtained from all participants. they were assured that their personal information would be kept confidential and that only general statistics and data would be published. 2.2. participants convenience sampling was used to select third-year nursing students who had completed their clinical clerkship at the time of the study (n=60). inclusion criteria were being interested in participating in research and completing an emergency course. participants were excluded from the study if they did not attend an educational session and did not complete the study’s second phase. using computerized random number generation software, participants were randomly assigned to either the intervention or the control group. 2.3. preparation of gamified triage we developed a theme game based on the framework of nursing competencies developed by the world health organization and the international council of nurses (www.who.int/disasternursing/framework_of_competences _09.pdf ). after a thorough study of existing software, two applications, articulate storyline 3 and carzytalk animator 4 were selected for the development of the game content and framework. articulate storyline 3 software is user-friendly and was developed by articulate global co. it is one of the most popular applications for electronic content design. this software has been used for the development of numerous electronic contents (15-17). crazytalk animator, developed by reallusion, was the platform for creating 2d animations. this software is easy to use and provides good quality results. it has been used in several studies for storyboarding and can be considered by researchers for creating animations. the first step in developing gamified triage was to define the functional and technical requirements, including modules, the design of a learning path, and a graphical user interface (gui). following this, the learning content was developed, including the information elements. based on a triage guide this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e77 and reference materials, the information elements for the learning content were developed (18-20). animation techniques and articulate storyline 3 software were used to create the interactive content. crazytalk animator v4 software was used to create the text content of each slide as a female character with facial, lip, and mouth movements that appeared on each slide. to learn both the auditory and visual parts of the scenario-based section, explanations were given using animated animations. as a reward for correctly answering the scenario questions, students received 4 triage coins produced by the content production team, which were counted at the end of this section. the game consisted of 25 scenarios organized into five categories. students could earn a total of 20 points or coins for each scenario. students would be returned to the beginning of the game if they scored less than 86 coins. here is a video of the designed content embedded in google drive: https://zaya.io/uew1q. 7 nursing and midwifery faculty members approved the scientific content of the crisis management game. in addition, two members of the smart university of medicine e-learning group reviewed the technical features of the content. the design of the game environment is shown in figure 2. 2.4. data gathering a questionnaire on demographic characteristics (age, gender, single child status, family residence, previous disaster/rescue experience, and previous participation in related training courses), disaster nurses’ knowledge questionnaire, and measurement checklists for disasters and crises were used to collect data in five stations. 3. procedure 3.1. preparation teaching precision requires identifying the target behavior, which must be determined precisely (9). to accomplish this, a written definition of the observable, physical movements of the behavior must be developed. the things we did for precision teaching include:1to identify and quantify the mastery of each catastrophe determined for the game, we developed task analyses that detailed the steps in the performance of each behavior. we explained the physical movements and materials required for each behavior. the task analysis involved a review of relevant clinical practice guidelines and consultation with an emergency nurse with over 20 years of experience. 2two senior clinicians with expertise in gbt were asked to assess and provide feedback regarding procedural skills training. they confirmed the validity of the task analysis. 3as a result, it was decided to establish a fluency criterion. the fluency criterion was established after a clinical professor performed each station three times with 100 percent accuracy, and the mean duration of these performances was used to determine the fluency criterion. this test was scored on a 100-point scale, with 20 points for each station (n=5). for each station, a fluency criterion required participants to perform the task with 100% accuracy without exceeding the expert’s mean duration by more than 10%. we administered the osce test immediately and one month after the intervention and compared the results of each test. behavioral fluency, as mentioned, has three components: durability, stability, and generalizability. concerning durability, we aimed to examine whether the intervention improved the pace and accuracy of participants in each crisis management scenario. regarding the component of generalizability or generalization to a new situation, the osce test was designed so that the topics of the osce stations were similar. however, parallel scenarios were used for this purpose so that the participant could test his or her acquired knowledge in them and show that he or she could apply it correctly in new situations with the same speed and accuracy. also, concerning the stability component, students’ performance in disaster and crisis management was evaluated in the presence of distractions to assess the stability of their behavior. a major distractor in clinical practice is communication irrelevant to the current clinical task. our distraction strategy consisted of interruption questions that had nothing to do with the current task (e.g., "tell me about the last book you read"). the interruption questions were asked in a standardized order and at a standardized time. questions were asked at one-minute intervals, and when participants gave short answers, they were reminded to provide more information. 3.2. pretest participants received a brief overview of the intervention and fluency criterion in two groups in the simulation laboratory and at the osce stations. each presentation of the simulated scenarios at the osce-1 stations in the pretest was a fluencybuilding trial. a trained observer observed each exercise during all tests and recorded the time. the procedure was to end as soon as participants completed the clinical report. participants were instructed to manage crisis situations "to the best of their ability," and one of the two trained observers was to rate the accuracy and pace of their performance. on the record sheet, the observers had to note whether each step was performed correctly or inaccurately. one observer provided corrective feedback to the participant at the end of the trial. the task analysis was given to the participants at the end of the trial. observers provided specific, detailed feedback to participants on the accuracy and pace of performance. the observer gave a detailed report of all steps performed incorrectly and the total number of steps performed. those who performed incorrect steps had the opportunity to practice this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masoumian hosseini et al. 4 them during the practical phase of the study. 3.3. posttest we conducted two posttests in the two groups after the intervention ended. the osce test was used to assess students’ behavioral fluency and durability. the osce test after the intervention was administered to both groups simultaneously in two phases: one week (osce-2) and one month (osce3) after the emergency and crisis management internship. the student’s performance was assessed using a five-station osce each time. the stations were designed based on five scenarios. ten disaster management experts and faculty members confirmed the validity of the checklists. inter-rater reliability between the two trained nursing educators with identical professional characteristics was also calculated by correlating the scores obtained by ten nursing students (who were not included in the main analysis). it was found that the icc coefficients of agreement between the educators were 0.92, indicating substantial agreement. the stations had a scenario, a guide, an examiner guide for the assessor, an assessment checklist, and a scenario for standard patients. in each station, one or more objectives were assessed using checklists created by the researchers. based on the objectives in each station, standard patients, mannequins, and equipment were used based on each station’s objectives. a coordinating committee reviewed all stations and equipment one day before the test. participants were told that one of two observers would rate their accuracy and performance duration. 3.4. disaster nurses’ knowledge questionnaire the test consisted of 15 multiple-choice questions (mcqs) on disaster preparedness, such as the definition of disasters (one item), types of disasters (two items), causes of disasters (three items), management of disasters (three items), and the role of hospital and emergency nurses in disasters (six items). according to the nurses’ knowledge questionnaire scoring system, each correct answer was scored one point, and each incorrect answer was scored zero points. the total score for knowledge was 15 points. the higher the score, the better the nurse’s knowledge. all participants were assessed before (pretest) and immediately after the theoretical phase of the intervention (posttest), using the questionnaire of disaster nurses’ knowledge. 3.5. internal consistency reliability in the study by khalil (2019), the reliability of the questionnaire was confirmed, and cronbach’s alpha was 0.76 (21). this study used a test-retest procedure to investigate the instrument’s reliability. a cronbach’s alpha coefficient of 0.81 was calculated and reported. phase 1: theoretical training intervention group the educational intervention was conducted for five weeks in a simulated university classroom, with a game-based case each week. the researchers used computer software to modify the contents and tasks of the game and to set scenes for students based on the game’s progress. there were various game elements, including cooperation, good scenes/stories, competition, resource management, questions, answers, time pressure, and feedback. the game was played in five sessions and included the following topics: 1. preparing medical and health resources for earthquake rescue 2. racing against time: triage, rescue, and treatment of five injured victims in a disaster area 3. providing comfort to injured family members through assessment and intervention in their psychological stress response 4. managing a patient with hemorrhagic shock 5. assessing and managing a patient with a head injury both the intervention and control groups used similar teaching scenarios in terms of content. the instructor was also the same in both groups. students participated in a crisis and disaster game each week under the supervision of a clinical professor. the following steps were followed for each game. each time, a two-hour session was scheduled and conducted with the disaster and crisis game, beginning with the student logging into the game and ending with the feedback. access to the game was through usernames and passwords assigned to each user. students received detailed instructions for the game from the researcher. once they logged into the computer, they could access the appropriate section of interactive learning content in the game. the teacher monitored the students’ activities, and the students received feedback on their games from the teacher. the game development team designed individual avatars for each student, and the teacher recorded and shared the results of each student session based on the avatars. to ensure confidentiality, students did not know each other’s avatars. the avatars and results were displayed on the university’s learning management system (lms) leaderboard as part of the competition. students received badges for playing and learning the scenarios, and those who received more than five were allowed to participate in the clinical phase. twenty-four hours after working through each scenario game, the students participated in a 90-minute debriefing in the shahidi conference room at nohomeday hospital in torbat heydariyeh. the clinical professor had attended a debriefing workshop and had the necessary experience to conduct debriefing sessions. the 3d model was used throughout the study, and all debriefing sessions followed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e77 international nursing association of clinical and simulation learning (inacsl) guidelines. control group in the control group, instruction was face-to-face. each two-hour session began with a case study of disaster conditions related to the lesson topics. during the discussion of the paper-based scenario, a clinical instructor discussed the educational objectives to be achieved by working with the scenario. he also asked questions to determine the all-encompassing prior knowledge of the case. after a brief introduction to the case by the clinical professor, students began working with the scenario. like the intervention group, the control group also received five weeks of theoretical training. each week, a disaster and crisis scenario was presented. phase 2: clinical training disaster & crisis internship in this phase, the intervention and control groups were each divided into five groups of six students (10 groups of six in total). internships and clinical training in the university’s clinical laboratories were conducted for four weeks with standardised patients and simulated emergencies and crisis situations. this phase was structured according to the four-step pazin model for each crisis case, which includes the steps of 1) briefing, 2) sequence, 3) feedback, and 4) repetition (22). during the briefing step, the trainer explains the scenario in front of the participants. during the sequence step, progressively more complex scenarios were presented, allowing participants to consolidate their knowledge and work at a higher level of training and learning. during the feedback step, the trainer acted as a facilitator, observing participants’ exercises and providing feedback as needed. debriefing is the heart of the feedback process. the trainer designed a non-threatening environment with open-ended questions and positive reinforcement to encourage participants to participate. as a final step, the trainer ensured that the knowledge learned during the training was retained during each training session through repetition and practice. during the internship phase, participants’ data (steps executed correctly, steps executed incorrectly, and execution duration) were used to create standard acceleration charts using chartlytics software (www.chartlytics.com). 3.6. statistical analysis spss software version 16.0 was used to analyze the data and examine the effects of game-based teaching on the behavioral fluency of nursing students in disaster management courses. shapiro-wilk and kolmogorov-smirnov tests were used to examine the natural distribution of quantitative variables. descriptive statistics such as mean, standard deviation, and frequency distribution were used to describe participants’ characteristics. analyzes were performed using inferential statistics (repeated measures analysis of variance (anova), independent t-test, paired t-test, chi-square). in this study, the significance level was considered to be p < 0.05. 4. result sixty-three nursing students participated in this study, most of whom were single (87.3%) and female (81.7%). the chisquare test showed that the intervention and control groups were homogeneous regarding gender. there was no significant difference in mean age between the intervention and control (20.75 ± 1.16 vs. 20.70 ± 1.16; p = 0.83; respectively). most participants (86.2%) had never experienced a disaster or rescue. this was the first time participants had attended a crisis management training program. 4.1. behavioral fluency a repeated measures anova was conducted to compare the fluency of the gbt group with that of the cbt group in the osce1 pretest, osce2 postintervention, and osce3 posttest (figure 3a). there was no significant difference in osce1 pretest scores between the cbt group and the gbt group. both groups obtained significantly different scores after one week (posttest1-osce2) and after one month (posttest2osce3) (p < 0.001 and p < 0.001, respectively; table 1). a paired t-test was used to compare the results between pretest, posttests 1, and posttest 2 both within and between the intervention and control groups. the paired t-test indicated statistically significant differences in both groups’ mean pretest and posttest scores1 (table 1). in posttest 1, one week after training, there was a significant difference between the pretest scores (16.27 ± 2.52) and posttest scores (69.23 ± 6.14) for the gbt group (p = 0.001). nevertheless, there was no statistically significant difference (p = 0.056) when comparing posttest scores one month after gbt (69.03 ± 6.09) with posttest scores one week after (69.23 ± 6.14). in addition, the highest scores were obtained in the cbt group 1 week after training (54.83 ± 6.61); these were significantly higher than the pretest scores (16.40 ± 2.27) (p < 0.001). in addition, there was a statistically significant difference between posttest 1 and posttest 2 scores in the cbt group. students’ behavioral fluency scores decreased significantly (p < 0.0001) one month after the intervention (47.97 ± 5.49) compared with one week after (54.83 ± 6.61) (table 2). 4.2. knowledge according to the results, the mean score of the theoretical test at baseline did not differ significantly between the study groups (p = 0.534). mean scores of students in gbt were significantly higher than those in cbt after training (p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masoumian hosseini et al. 6 table 1: comparing the knowledge and behavioral fluency scores between game-based (intervention) and case-based (control) groups during pretest, posttest 1, and posttest 2 groups intervention control p value behavioral fluency scores pretest 16.27± 2.518 16.40 ± 2.268 0.8301 posttest 1 69.23 ± 6.140 54.83 ± 6.608 <0.0001 posttest 2 69.03 ± 6.088 47.97 ± 5.493 <0.0001 knowledge scores pretest 12.43 ± 3.901 11.83 ± 3.524 0.5344 posttest 74.17 ± 6.492 53.10 ± 9.038 <0.0001 data are presented as mean ± standard deviation. table 2: the comparison of the behavioral fluency scores within game-based (intervention) and case-based (control) groups in pretest and posttests (1 and 2) paired tests mean p value pretest posttest 1 posttest 2 mean of differences ± sd control posttest 1-pretest 16.40 54.83 38.43 ± 6.971 <0.0001 posttest 2-pretest 16.40 47.97 31.57 ± 5.987 <0.0001 posttest 1-posttest 2 54.83 47.97 6.867 ± 2.193 <0.0001 intervention posttest 1-pretest 16.27 69.23 52.97 ± 6.764 <0.0001 posttest 2-pretest 16.27 69.03 52.77 ± 6.689 <0.0001 posttest 1-posttest2 69.23 69.03 0.2000 ± 0.550 0.0563 < 0.001). mean scores of both groups increased significantly after training compared to baseline (p < 0.001 for gbt, p < 0.001 for cbt; table 1 & figure 3b). 5. discussion in the current study, which aimed to examine how gbt with precision teaching affects the behavioral fluency and knowledge of nursing students, a significant improvement in their knowledge of disaster and crisis management was found. furthermore, behavioral fluency of acquired clinical decision-making skills in disaster situations remained unchanged after one month of the intervention compared to one week after the intervention. thus, the results support the hypothesis that nursing students can improve their knowledge and behavior fluency in crisis & disaster management through the game. results showed that gbt students had higher theoretical test scores than cbt students. although both groups’ theoretical test scores increased after the intervention, the increase was more pronounced for the gbt group. thus, throughout the instruction and theory phase, students improved their disaster knowledge. the control group’s scores on self-assessed knowledge were lower than those of the intervention group, possibly due to an improvement in students’ intrinsic motivation to achieve the game goal. games can provide an enjoyable and relaxing environment for learning and practice, in contrast to the psychological feeling of uncertainty that students experience during scenario simulation (23). the result shows that most students in both groups lacked knowledge of crisis and disaster management before the study. similar to the current study, a study in jordan (2012) examined nurses’ perceptions of crisis management and concluded that nurses’ preparedness to deal with crisis situations was generally low (24). in addition, this study showed that nurses have lower knowledge of disaster preparedness than their clinical skills. the study by hajjavi (2009) in zanjan hospitals showed that 76.8% of managers and supervisors had unacceptable knowledge regarding crises and disasters (25). in this context, according to latifi (2019), crisis management education programs could reduce the mortality rate of those injured in a disaster (26). this is because such programs promote awareness of the programs available to manage disasters among hospital staff, increase staff’s participation in planning and solving existing problems, and improve staff’s competence in performing their assigned tasks. according to the study by sharifzadeh (2020), "play and learn for surgeons" improved surgical instrument handling and knowledge of obstetrics and gynaecology residents during uterine artery ligation surgeries (27). in another study, the use of "periopsimtm instrument trainer" and "periopsimtm for burr hole surgery" in neurosurgery residents significantly improved outcomes, saved time, and reduced erthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e77 figure 1: the flow diagram illustrates the activities that occurred during this study. the study was conducted in two phases: an educational and an internship phase. in the educational phase, students were randomly assigned to the intervention and control groups, and two teaching methods were used. in the internship phase, students were reassigned to groups and received the same clinical education. grouping was done in groups of 6; 5 standardized patients were used to implement the 5-stage pazin model in the simulation. osce: objective structured clinical examination. rors in identifying neurosurgical instruments during simulated burr hole surgeries (28). the ma (2021) study examined the effects of themed games and scenario simulations on nursing students’ disaster nursing competence and found that nursing students in the group taught by theme games had significantly higher disaster nursing competence scores (29). another disaster training study found that students understood mass casualty incidents (mcis) and teamwork better by playing an escape room game (30). studies have shown that serious games significantly impact student learning and skills in disaster nursing. cpr training is one area where games effectively improve students’ disaster nursing skills (31). the results of the current study regarding the effects of game-based training on behavioral fluency and knowledge of nursing students in the field of crisis & disaster management are similar to those of the studies reviewed; however, the comparison should be made with caution because of differences in the populations studied, the game objectives and designs, and the methods used to assess trainee performance. accordingly, there was no statistical difference between the intervention and control groups on the osce pretest bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masoumian hosseini et al. 8 figure 2: design of the game environment using articulate storyline 3 software. the design of the training sections and the question scenarios are shown in this combined image. figure 3: (a) graph of repeated measures for the effect of education on student performance. (b) comparison of students’ knowledge scores in gbt and cbt. (c) comparison of objective structured clinical examination (osce) test scores at three-time points in the intervention and control groups. ci: confidence interval; k: knowledge; i: intervention group; c: control group. fore the internship phase. accordingly, the game did not significantly affect students’ performance in theory classes. although both groups received the same clinical training, the better performance of students in the game group after the internship phase in osce posttest 1 and posttest 2 suggests that the game may help reduce negative cognitive load during clinical training. therefore, it is likely that training through games can reduce the effects of stress in critical situations, leading to an increase in performance stability, as demonstrated in posttests 2 and 3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e77 6. limitations first, a limitation of the present study was the lack of training facilities and equipment. hospitals that had already conducted crisis management workshops were consulted to address the equipment shortage problem. second, since disasters are unpredictable, hospitals and regions have specific needs based on anticipated and unanticipated disasters, making generalizations difficult. therefore, the results of this study should not be generalized to other hospitals or regions because they are based on data from a single geographic area. in order to evaluate gbt incorporating precision teaching, more robust experimental designs are needed. however, implementing such designs in a clinical environment may be challenging. 7. conclusion nursing trainees gained behavioral fluency in disaster and crisis management through gbt with frequency building and precision teaching. observations indicate that the intervention yielded a level of performance learning that was retained was stable and appeared to transfer to the simulated real-world setting. a review of the results of the present study indicates that nursing students’ knowledge and behavioral fluency regarding crisis management were more effectively improved by using the disaster and crisis game than by using a case-based method. disaster and crisis games can help nursing students develop skills in this area. however, further long-term studies with larger sample sizes are needed to confirm this finding. in medical education, fluency training and precision teaching should be further explored. 8. declarations 8.1. acknowledgments it is with great pleasure that we thank the nursing students and faculty members of torbat heydariyeh university of medical sciences (thums) for their contributions to this project. 8.2. authors’ contributions t.m.h., and m.m.h. wrote the manuscript draft. t.m.h. & m.m.h & k.q. designed the study. m.m.h. did the data gathering. n.b conducted the analyses. all authors reviewed and approved the manuscript. 8.3. conflict of interest the authors have no conflicts of interest. 8.4. fundings and supports this research was supported by the vice-chancellor of the smart university of medical sciences (no. 321). 8.5. data availability upon a reasonable request, the corresponding author can provide the data set that was analyzed during this study. references 1. xue cl, shu ys, hayter m, lee a. experiences of nurses involved in natural disaster relief: a meta-synthesis of qualitative literature. j clin nurs. 2020;29(23-24):451431. 2. binder c. behavioral fluency: evolution of a new paradigm. behav anal today. 1996;19(2):163-97. 3. lydon s, burns n, healy o, o’connor p, mcdermott br, byrne d. preliminary evaluation of the efficacy of an intervention incorporating precision teaching to train procedural skills among final cycle medical students. bmj simul technol enhanc learn. 2017;3(3):116. 4. calkin ab. precision teaching: 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2021;103:104923. 30. nybo, s. e, klepser s a, klepser m. design of a disaster preparedness escape room for first and second-year pharmacy students. curr pharm teach learn. 2020; 12 (6): 716-723. 31. farsi z, yazdani m, butler s, nezamzadeh m, mirlashari j. comparative effectiveness of simulation versus serious game for training nursing students in cardiopulmonary resuscitation: a randomized control trial. int j comput games technol. 2021;2021 (6695077): 1-12. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods procedure result discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e79 or i g i n a l re s e a rc h clinical prediction score for successful weaning from noninvasive positive pressure ventilation (nippv ) in emergency department; a retrospective cohort study sittichok leela-amornsin1, chavin triganjananun1, chaiyaporn yuksen2∗, chetsadakon jenpanitpong2, sorawich watcharakitpaisan2 1. chakri naruebodindra medical institute, faculty of medicine ramathibodi hospital, mahidol university, 111 moo 14, bang pla, bang phli, samut prakarn 10540, thailand. 2. department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, bangkok, thailand. received: july 2022; accepted: august 2022; published online: 2 october 2022 abstract: introduction: due to the lack of in-hospital beds, some patients with acute cardiogenic pulmonary edema are initiated and weaned off noninvasive positive pressure ventilation (nippv ) at the emergency department (ed). this study aimed to develop a clinical score to predict successful weaning from nippv in these patients. methods: this retrospective cohort study was conducted on patients with acute cardiogenic pulmonary edema who received nippv at the ed of ramathibodi hospital, bangkok, thailand. multivariable logistic regression analysis was used to developed a predictive model for weaning from nippv. results: 355 patients with acute cardiogenic pulmonary edema treated with nippv were studied (107 (30.14%) failed to be weaned). the significant risk factors of weaning failure based on multivariate analysis were age > 75 years (or: 3.1, 95% ci: 1.15–8.33, p = 0.025), pneumonia (or: 2.72, 95% ci: 1.39–5.31, p = 0.003), pulse rate > 80 bpm before nippv (or: 1.74, 95% ci: 1.04–2.91, p = 0.033), and a urinary output < 150 cc/h while using nippv (or: 2.93, 95% ci: 1.74–4.91, p < 0.001). in addition, clinically significant risk factors for weaning from nippv were age 60 – 75 years, respiratory rate > 26 breaths/min before weaning and oxygen saturation of < 97% as assessed by pulse oximetry before weaning from nippv. since the lowest coefficient obtained was 0.46, the scores were split into groups of 0.5 points for each factor. based on the area under the receiver operating characteristic (roc) curve (71.3% (95% ci: 66.0–75.7%)), the cut point of risk score was divided into the low-risk with positive likelihood ratio of 0.48 (95% ci 0.33–0.69, p <0.001), the moderate-risk with positive likelihood ratio of 0.74 (95%ci 0.52–1.05, p = 0.080), and the high-risk group with positive likelihood ratio of 3.41 (95%ci 2.39–4.88, p <0.001) for predicting weaning failure. conclusion: in patients with acute cardiogenic pulmonary edema under the nippv, weaning is associated with a significant increasing risk of failure in age >75, presence of pneumonia, heart rate > 80 bpm before weaning, and urinary output < 150 cc/h during ventilation. based on the designed model in this study, patients with score ≤ 3.5, 4–5, and > 5 points were in low, moderate, and severe risk of weaning failure, respectively. keywords: noninvasive ventilation; ventilator weaning; continuous positive airway pressure; emergency service, hospital; intubation cite this article as: leela-amornsin s, triganjananun c, yuksen c, jenpanitpong c, watcharakitpaisan s. clinical prediction score for successful weaning from noninvasive positive pressure ventilation (nippv ) in emergency department; a retrospective cohort study. arch acad emerg med. 2022; 10(1): e79. https://doi.org/10.22037/aaem.v10i1.1769. ∗corresponding author: chaiyaporn yuksen; department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, 270 rama vi road, thung phaya thai, ratchathewi, bangkok, thailand, 10400. email: chaipool0634@hotmail.com, orcid: https://orcid.org/0000-0002-48907176. 1. introduction acute cardiogenic pulmonary edema is a common cause of referring to emergency departments (eds) worldwide. in the united states, approximately 6 million patients have acute cardiogenic pulmonary edema annually (1, 2). at ramathibodi hospital, thailand, more than 450 patients are diagnosed with acute cardiogenic pulmonary edema annually and require a noninvasive ventilator. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. leela-amornsin et al. 2 the clinical diagnostic criteria for diagnosing acute cardiogenic pulmonary edema based on the european society of cardiology (esc) guidelines are as follows: acute respiratory distress (acute increase in the work of breathing, considerable tachypnea, respiratory rate > 25 breaths/min, use of accessory muscles, or abdominal paradox), findings from a physical examination (crackles plus wheezing in the lungs or a third heart sound), and history of orthopnea and respiratory failure (oxygen saturation in room air by pulse oximetry < 60 mmhg, paco2 > 45 mmhg, or pao2/ fraction of inspired oxygen (fio2) < 300 mmhg) (3). the diagnostic confirmation of acute cardiogenic pulmonary edema consists of at least two of the following: clear signs of pulmonary congestion on chest radiography or a computed tomography scan; multiple b-lines ≥ 3; b-lines in two chest zones on each hemithorax as shown by lung ultrasound; elevated pulmonary capillary pressure on catheterization; increased total lung water on pulse contour and a thermodilution analysis system; signs of elevated filling pressure on echocardiography; and a significant elevation in natriuretic peptide concentrations (bnp > 400pg/ml or n-probnp > 900pg/ml [or 1800pg/ml in > 75 years]). there are various etiologies of acute cardiogenic pulmonary edema, such as cardiac ischemia, acute coronary disease, valvular heart disease, hypertensive emergency, arrhythmias, and tamponade (4). symptoms of this condition include dyspnea, shortness of breath, leg edema, and desaturation (5-7). if a patient has mild symptoms of pulmonary edema, treatment involves oxygenation, a vasodilator drug, or a diuretic drug (1). in more severe cases, a noninvasive ventilator is applied to the patient to support ventilation and decrease the work of the breathing muscles. noninvasive ventilators continuously create positive airway pressure, decrease venous return to the heart, decrease afterload, reduce left ventricular pressure, and improve clinical outcomes in patients with acute cardiogenic pulmonary edema (8-10). moreover, using noninvasive ventilators reduces intubation rate, the risk of post-intubation complications (e.g., infection, barotrauma, laryngeal edema, and tracheal stenosis), and hospital mortality in severe acute cardiogenic pulmonary edema (9, 11). therefore, noninvasive ventilators are useful for treating acute cardiogenic pulmonary edema and have been suggested as the first-line strategy. when the patients’ clinical outcome improves, they can be weaned off the noninvasive ventilator. currently, ramathibodi hospital is experiencing the problem of a limitation of inpatient beds. this situation has led to ed overcrowding with critical patients receiving noninvasive ventilation, including those with acute cardiogenic pulmonary edema. treatment is performed in a resuscitation zone, including weaning from noninvasive ventilation in acute cardiogenic edema. noninvasive ventilation’s rate of weaning failure (patients continue noninvasive ventilation or are intubated after weaning from noninvasive ventilation) is > 250 cases/year. disadvantages of prolonged use of a noninvasive ventilator include gastric distension, aspiration, hypotension and coughing (12). a weaning failure can make patients feel uncomfortable. there is still a lack of evidence for using parameters to improve judgment and a successful outcome of weaning from noninvasive ventilation. this study aimed to develop a clinical score to predict the risk of failure to wean from noninvasive positive pressure ventilation (nippv ) in patients with cardiogenic pulmonary edema. 2. methods 2.1. study design and setting this is a retrospective cohort study to design a diagnostic prediction model, which was conducted on patients with acute cardiogenic pulmonary edema who received nippv for treatment at the ed of ramathibodi hospital, a universityaffiliated super tertiary care hospital in bangkok, thailand, from january 2017 to december 2019. this study was approved by the faculty of medicine, committee on human rights related to research involving human subjects, ramathibodi hospital, mahidol university (coa. no mura2020/972). the ethics committee waived obtaining consent for this research as the patients’ medical records were used for data gathering and a statement covering patient data confidentiality and compliance with the declaration of helsinki was provided. 2.2. participants we included patients with acute cardiogenic pulmonary edema who received nippv for treatment and weaning from nippv was attempted at the ed. data were collected from the ramathibodi hospital database and emergency medical records. the eligibility criteria were patients older than 18 years, a clinical diagnosis of acute respiratory failure caused by acute cardiogenic pulmonary edema based on esc criteria, and the requirement of noninvasive ventilation and weaning from noninvasive ventilation at the ed. the exclusion criteria were use of noninvasive ventilation within the previous 24 hours, hospitalization due to trauma or having a history of surgery in facial/oral/trachea/laryngeal areas within the past one month, hemodynamic instability, inability to protect the airways, excessive secretion, lack of cooperation, inability to fit the mask, and receiving hemodialysis or peritoneal dialysis during treatment. 2.3. data gathering and outcome measures the variables for determining clinical scoring of successful weaning from noninvasive ventilation were recorded for all this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e79 figure 1: left: comparing the risk scores between patients with and without successful weaning from non-invasive positive pressure ventilation (nippv ). right: area under the receiver operating characteristic (roc) curve of model in predicting the risk of weaning failure from nippv in emergency department. circle: the measures of calibration. eligible patients, including baseline characteristics and potential clinical factors for successful weaning from noninvasive ventilation. initial vital signs (respiratory rate, blood pressure, heart rate, body temperature, and spo2) were measured when the patient arrived at the triage zone of the ed. vital signs before weaning were measured before deciding to discontinue nippv for the patient. laboratory variables (white blood cell count, hemoglobin, hematocrit, creatinine, blood urea nitrogen, sodium, potassium, and pro b-type natriuretic peptide (pro-bnp)) were measured within 30 mins after the patient arrived at the ed. the first troponin blood test was collected 30 minutes after the patient arrived at the ed, and the second test was collected 3 hours later. the arterial blood gases (ph, pao2, paco2, hco3, lactate, oxygen saturation) were measured before the patient applied nippv and within 90 minutes before discontinuing nippv. the door to nippv was recorded as the time interval between when the patient arrived at the ed and when nippv was applied. the duration of nippv was the total time the patient was using nippv in ed. the setting of nippv (mode of nippv, inspiratory pressure, expiratory pressure, pressure support, positive endexpiratory pressure (peep), fio2) was recorded when the emergency resident or emergency physician initiated and before weaning of nippv. the diuretic dose was the accumulated dose of furosemide that the patient was given while receiving nippv. the urinary output was the total amount of urine during the period the patient received nippv. the cardiologist or emergency physician measured the ejection fraction (ef) during the period the patient received nippv. 2.4. definitions weaning success: after discontinuing nippv, the patient wasn’t decided to reinitiate bilevel positive airway pressure (bipap) or undergo endotracheal intubation within 24 hours. weaning failure: after stopping nippv, the patient was decided to reinitiate bipap or undergo endotracheal intubation within 24 hours. 2.5. statistical analysis twenty-eight (77.8%) patients had successful weaning from nippv, and eight (22.2%) patients had weaning failure, based on our pilot study. the ratio of success to failure to wean from nippv was 2.5:1. stata software version 14.0 was used to calculate the required sample size by using a two-sample comparison of success and failure to wean from nippv. the assumptions were as follows: alpha = 0.05 (two-sided test), the power of the sample size = 0.8, the ratio of the sample size = 2.5:1 and the level of statistical significance was < 0.05. the minimum number of patients required to determine statistical significance for each variable was calculated. a sample size of 247 was required for patients in the nippv weaning success group, and a sample size of 99 was required for patients in the nippv weaning failure group. data were analyzed using stata version 14.0. the findings are presented as mean standard deviation, frequency (%), or median (inter quartile range). all study variables were compared between the nippv weaning success group and the nippv weaning failure group using the exact probability test for categorical variables and the t-test for continuous variables. the predictive power of each variable was calculated using univariate logistic regression and presented as the area this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. leela-amornsin et al. 4 table 1: comparing the baseline characteristics of participants between cases with and without successful weaning from non-invasive positive pressure ventilation (nippv ) characters successful (248) unsuccessful (107) p value age (years) mean ± sd 75.1 ± 12.5 78.1 ± 11.1 0.011 < 60 years 35 (14.1) 6 (5.6) 60-75 years 67 (27.0) 23 (21.5) 0.017 > 75 years 146 (58.9) 78 (72.9) gender male 92 (37.1) 28 (26.2) 0.051 underlying disease asthma/copd 25 (10.1) 14 (13.1) 0.460 bronchiectasis 5 (2.0) 1 (0.9) 0.673 congestive heart failure 70 (28.2) 31 (29.0) 0.898 ischemic heart diseases 118 (47.6) 39 (26.5) 0.062 valvular heart diseases 86 (34.7) 42 (39.3) 0.470 chronic renal failure 119 (48.0) 48 (44.9) 0.643 neoplasm 26 (10.5) 10 (9.4) 0.849 diabetes mellitus 135 (54.4) 57 (53.3) 0.908 hypertension 206 (83.1) 91 (85.1) 0.755 initial vital signs respiratory rate (/min) 28.8 ± 5.9 29.3 ± 7.4 0.480 systolic blood pressure (mmhg) 156.4 ± 34.4 148.2 ± 32.2 0.036 diastolic blood pressure (mmhg) 82.0 ± 16.8 76.4 ± 14.2 0.003 heart rate (bpm) 93.8 ± 22.6 94.7 ± 22.1 0.739 body temperature (°c) 36.9 ± 0.7 37.1 ± 0.9 0.013 spo2 (%) 92.0 ± 7.8 91.2 ± 7.4 0.378 vital signs before weaning respiratory rate (/min) 21.8 ± 2.2 22.5 ± 2.8 0.023 rr > 26 breaths/min 9 (3.6) 9 (8.4) 0.056 systolic blood pressure (mmhg) 139.6 ± 24.0 139.4 ± 23.5 0.936 diastolic blood pressure (mmhg) 73.9 ± 13.4 72.6 ± 14.1 0.390 heart rate (bpm) 80.3 ± 17.0 84.0 ± 18.1 0.065 heart rate > 80 bpm 117 (47.2) 62 (57.9) 0.040 body temperature (°c) 36.9 ± 0.7 37.2 ± 0.4 0.268 spo2 (%) 98.8 ± 1.7 98.4 ± 2.1 0.054 spo2 < 97% 28 (11.3) 19 (17.8) 0.072 laboratory values white blood cell count (cell/mm3) 8810.4 ± 5397.5 9083.8 ± 4426.0 0.645 hemoglobin (g/dl) 10.8 ± 2.4 10.4 ± 2.1 0.073 hematocrit (%) 32.8 ± 7.5 32.7 ± 6.2 0.165 creatinine (mg/dl) 2.2± 2.7 1.7 ± 1.3 0.095 blood urea nitrogen (mg/dl) 33.0 ± 22.0 31.0 ± 18.8 0.415 sodium (mmol/l) 137.1 ± 5.9 136.1 ± 5.7 0.167 potassium (mmol/l) 4.3 ± 0.6 4.2 ± 0.7 0.409 pro-bnp (pg/ml) 5771 (2245 11408) 4774 (2339 -12108) 0.819 troponin change > 20% (0, 3 h) 37 (21.4) 8 (11.8) 0.099 nippv door to nippv (h) 0 (0 1) 1 (0 2) 0.093 duration of nippv (h) 6 (4 11) 8 (4 13) 0.248 initial setting of nippv psv (cmh2o) 13.2 ± 1.9 13.1 ± 1.5 0.736 peep (cmh2o) 6.7 ± 0.8 6.7 ± 0.8 0.706 fio2 0.4 ± 0.2 0.4 ± 0.2 0.642 setting of nippv before weaning bipap mode before nippv 165 (66.5) 80 (74.8) 0.135 psv (cmh2o) 12.4 ± 2.3 12.3 ± 2.4 0.582 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e79 table 1: comparing the baseline characteristics of participants between cases with and without successful weaning from non-invasive positive pressure ventilation (nippv ) characters successful (248) unsuccessful (107) p value cpap mode before nippv 69 (27.8) 26 (24.3) 0.517 peep (cmh2o) 6.5 ± 1.1 6.5 ± 1.0 0.924 fio2 0.4 ± 0.1 0.4 ± 0.1 0.189 diuretic usage dose of diuretic (mg) 80 (40 -120) 80 (40 -120) 0.295 urinary output (ml) 1500 (1100 -2200) 1300 (800 2000) 0.041 urinary output/h (ml/h) 236.5 (150 394) 165 (100 300) 0.001 urinary output < 150 cc/h 57 (23.0 ) 50 (46.7) <0.001 ejection fraction ≥ 50% 82 (38.1) 47 (48.0) 41-50% 54 (25.1) 24 (24.5) 0.206 ≤ 40% 79 (36.7) 27 (27.6) functional class (nyha) 1 2 (0.8) 0 (0.0) 2 30 (12.1) 14 (13.1) 0.632 3 130 (52.4) 50 (46.7) 4 86 (34.7) 43 (40.2) comorbidities pneumonia 22 (8.9) 26 (24.3) <0.001 anemia 73 (29.4) 41 (38.3) 0.108 volume overload 70 (28.2) 22 (20.6) 0.147 tracheobronchitis 7 (2.8) 8 (7.5) 0.079 asthma/copd 12 (4.8) 10 (9.4) 0.148 sepsis 17 (6.9) 15 (14.0) 0.042 acute renal failure 50 (20.2) 24 (22.4) 0.670 arterial blood gases before nippv arterial ph 7.40 ± 0.09 7.41 ± 0.06 0.661 paco2 (mmhg) 37.6 ± 14.7 33.7 ± 7.4 0.369 pao2 (mmhg) 104.0 ± 71.0 103.7 ± 58.1 0.989 hco3 (mmol/l) 21.7 ± 5.3 22.8± 4.5 0.323 lactate (mmol/l) 2.6 ± 2.1 2.3 ± 2.0 0.667 arterial blood gases before weaning from nippv (≤ 90 min) arterial ph 7.44 ± 0.0 7.41 ± 0.01 0.103 paco2 (mmhg) 40.5 ± 11.8 42.8 ± 12.0 0.562 pao2 (mmhg) 116.1 ± 52.5 152.3 ± 99.4 0.133 hco3 (mmol/l) 25.8 ± 5.8 26.2 ± 6.6 0.827 lactate (mmol/l) 1.4 ± 1.0 1.5 ± 0.7 0.682 data are presented as mean ± standard deviation (sd), frequency (%), and median (inter quartile range). sd: standard deviation, copd: chronic obstructive pulmonary disease, bpm : beats per minute, rr: respiratory rate, h: hours, pro-bnp: pro b-type natriuretic peptide, nippv: noninvasive positive pressure ventilation, bipap: bi-level positive airway pressure, psv: pressure support ventilation, cpap: continuous positive airway pressure, peep: positive end expiratory pressure, nyha: new york heart association, paco2: partial pressure of carbon dioxide, pao2: partial pressure of oxygen, fio2: fraction of inspired oxygen. under the receiver operating characteristic (auc) curve with 95% confidence intervals (ci). the potential predictors were categorized into three levels based on multivariable logistic regression. the regression coefficients of each clinical predictor were divided by the smallest coefficient and rounded to the nearest 0 or 0.5. discrimination in the prediction of successful weaning scores is shown by the area under the roc curve and 95% cis. the calibration of the prediction was determined using the hosmer–lemeshow goodness-of-fit test, and the number and percentages in each group are presented as the positive likelihood ratio, 95% cis, and p values. 3. results 3.1. baseline characteristics of studied cases 395 patients with acute cardiogenic pulmonary edema who were treated with nippv and had available information on weaning from nippv at the ed were studied. 40 patients were excluded (34 patients received hemodialysis or peritoneal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. leela-amornsin et al. 6 table 2: multivariable logistic regression analysis of risk factors associated with weaning failure of non-invasive positive pressure ventilation (nippv ) predictors or 95% ci p value coefficient* score age (year) < 60 1.00 reference 0 60-75 2.04 0.70-5.93 0.189 1.11 2.5 > 75 3.10 1.15-8.33 0.025 1.56 3.5 pneumonia no 1.00 reference 0 yes 2.72 1.39-5.31 0.003 0.93 2 rr > 26 breaths/min no 1.00 reference 0 yes 2.65 0.91-7.73 0.075 1.45 3 hr > 80 bpm no 1.00 reference 0 yes 1.74 1.04-2.91 0.033 0.46 1 o2 saturation < 97% no 1.00 reference 0 yes 1.88 0.94-3.76 0.073 0.66 1.5 urinary output < 150 cc/h no 1.00 reference 0 yes 2.93 1.74-4.91 < 0.001 0.77 1.5 coefficients were obtained from multivariable binary logistic regression. the lowest coefficient obtained using multivariable logistic regression was 0.46, and the scores were split into groups of 0.5 points for each risk factor. or: odds ratio; ci: confidence interval; reference: reference category. rr: respiratory rate, hr: heart rate. dialysis during nippv, 6 patients had used nippv within the previous 24 hours). finally, 355 patients were enrolled, (248 (69.85%) patients were successfully weaned off nippv, and 107 (30.14%) patients were not successfully weaned (intubation or re-use of nippv within 24 hours). table 1 compares the patients’ baseline characteristics between cases with successful and unsuccessful weaning from nippv in ed. older patients had a significantly higher rate of nippv weaning failure than younger patients (p = 0.017). there was no statistically significant correlation between nippv success or failure and underlying diseases, laboratory results collected 30 minutes after the patient arrived at eds, the initial setting of nippv, setting of nippv before weaning, ejection fraction, functional class (new york heart association; nyha), arterial blood gases before nippv and before weaning from nippv. the comorbidity of pneumonia, and sepsis was associated with a significantly higher incident of weaning failure (p < 0.001, and p = 0.042, respectively). patients with a heart rate > 80 beats per minute and a respiratory rate > 26 breaths/minutes before weaning from nippv had a successful nippv weaning rate of 47.2% (p = 0.040) and 3.6% (p = 0.056), respectively. the urine output during the period of nippv < 150 cc/hours had a higher incidence in the weaning failure group (46.7% vs. 23%, p < 0.001). figure 2: comparing observed and predicted risks of failure to weaning from non-invasive pressure ventilation (nippv ) in the studied cases. 3.2. multivariable logistic regression analysis in multivariable logistic regression analysis (table 2), the statistically significant risk factors (p < 0.05) of weaning failure were patients older than 75 years (odds ratio [or]: 3.1, 95% ci: 1.15–8.33, p = 0.025), pneumonia (or: 2.72, 95% ci: 1.39–5.31, p = 0.03), pulse rate > 80 bpm before nippv (or: 1.74, 95% ci: 1.04–2.91, p = 0.033), and a urinary output < 150 cc/h while using nippv (or: 2.93, 95% ci: 1.74–4.91, p < 0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e79 table 3: probability categories of the non-invasive positive pressure ventilation (nippv ) weaning failure score probability score nippv weaning lr+ 95% ci p value failure (107) success (248) low ≤ 3.5 25 (23.36) 121 (48.79) 0.48 0.33-0.69 < 0.001 moderate 4-5 29 (27.10) 91 (36.69) 0.74 0.52-1.05 0.080 high > 5 53 (49.53) 36 (14.52) 3.41 2.39-4.88 < 0.001 lr+: positive likelihood ratio; ci: confidence interval. in addition, clinically significant risk factors for failure of weaning from nippv were age 60 – 75 years, respiratory rate > 26 breaths/min before weaning, and oxygen saturation of < 97% as assessed by pulse oximetry before weaning from nippv. 3.3. designing a predictive model the lowest coefficient obtained using multivariable logistic regression was 0.46, and the scores were split into groups of 0.5 points for each risk factor. as a result, patients aged < 60 years had no points, those aged 60–75 years had 2.5 points, and those aged > 75 years had 3.5 points. patients with pneumonia had 2 points, those with a respiratory rate > 26 breaths/min before nippv had 3 points, those with a pulse rate > 80 bpm before nippv had 1 point, and those with an oxygen saturation by pulse oximetry < 97% had 1.5 points, and those with a urinary output < 150 cc/h while using nippv had 1.5 points (table 2). the mean score of patients with unsuccessful weaning from nippv were significantly higher (5.37 ± 1.87 vs. 4.0 ± 1.63; p < 0.001). figure 1(left) compares the risk scores between cases with and without successful weaning from nippv. to create the model, the failure to weaning risk score from nippv was assessed for each patient and the area under the roc curve was 71.3% (95% ci: 66.0–75.7%) figure 1(right). based on the area under the roc curve, the cut point of risk score was divided into three categories (table 3). the low-risk group had a positive likelihood ratio of 0.48 (95% ci 0.33–0.69, p <0.001), the moderate-risk group had a positive likelihood ratio of 0.74 (95%ci 0.52–1.05, p = 0.080), and the high-risk group had a positive likelihood ratio of 3.41 (95%ci 2.39–4.88, p <0.001) for weaning failure (table 3). figure 2 compares the observed and predicted risk of failure to wean from non-invasive pressure ventilation in the studied cases. 4. discussion although nippv is the first-line treatment for acute respiratory distress induced by acute cardiogenic pulmonary edema, evidence and the treatment protocol for this condition are still insufficient. in this study, multivariate analysis showed that the likelihood of failure in weaning from nippv among patients with acute cardiogenic pulmonary significantly increased in those aged > 75 years, those with pneumonia, those with a heart rate > 80 bpm before weaning, and those with a urinary output < 150 cc/h during nippv use. other clinically significant risk factors for failure in weaning from nippv were age 60 – 75 years, respiratory rate > 26 breaths/min before weaning, and oxygen saturation of < 97% as assessed by pulse oximetry before weaning from nippv. based on the framingham heart study, which reports the average annual incidence of acute cardiogenic pulmonary edema, we used the cut point of age at more than 60 years (13). we used the cut point of the respiratory rate at 26 bpm based on the recommendations for the initial treatment of acute heart failure with nippv in patients with respiratory distress (rr >25 breaths/min and spo2 < 90%) (14). tachycardia was associated with failure to wean from nippv (15)(2). a 20% increase in cardiac troponin led to the diagnosis of acute myocardial infarction that may precipitate worsening symptoms of acute heart failure (16). furthermore, regarding the urinary output, we used the recommendation of european society of cardiology 2022 that the appropriate management of diuretic therapy in a patient with acute heart failure was to monitor the urine output of more than 150 cc/h (14). we also found that when patients undergoing nippv weaning were assessed using a risk score, a score of ≤ 5 (low or medium risk) enhanced their probability of successful weaning from nippv. low-risk patients had a 0.48 likelihood of failing to wean from nippv. this group of patients reacted favorably to therapy. this finding suggests that, in patients with acute cardiogenic pulmonary edema who present to the ed for risk score evaluation, nippv can be discontinued to decrease the risk of nippv complications and to alleviate overcrowding in eds, which must cater to a high volume of critically ill patients. moderate-risk patients had a 0.74 likelihood of failing to wean from nippv. while risk ratings were predictive of successful weaning from nippv in this group of patients, the differences were not significant. as a result, when treating this group of individuals, if resources are not required for other critically ill patients, nippv should be continued until the patient’s overall risk factor score shifts to a low-risk score. at this point, nippv should be discontinued. however, resources are constrained if there are constraints such as overcrowding this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. leela-amornsin et al. 8 in the ed. weaning from nippv and continuing to evaluate the prognosis of the disease closely in the ed is essential. if there is a likelihood that a patient cannot be weaned successfully from nippv, nippv must be restarted. patients at high risk had a 3.41 times greater likelihood of failing to wean off nippv. in this situation, nippv treatment should be continued until the patient’s total risk score falls to moderate or low. weaning from nippv should then be considered with close follow-up. this study showed that increasing age increased the risk of weaning failure of nippv, particularly in patients aged > 75 and 60–75. no studies had shown evidence of an age-related risk factor for weaning failure. therefore, risk factors for failure of weaning from nippv require further investigation. felker et al. studied the amount of diuretic administered to patients and found no effect on acute cardiogenic pulmonary edema therapy (17). in our study, the amount of diuretic used was the same in the nippv weaning success and failure groups. this finding is because the primary factor affecting patients’ dyspnea and the effectiveness of weaning from nippv was the volume of urine produced by the patients, not the amount of diuretic administered. in this study, the most significant risk factor for weaning failure of nippv was a urinary output < 150 cc/h during nippv. acute cardiogenic pulmonary edema is caused by an accumulation of fluid in the alveoli and interstitial space (9). if a patient has a urinary output < 150 cc/h in the first 6 hours, diuretics and urinary output are increased to minimize the amount of volume overload. this is consistent with current heart failure therapy guidelines. this study showed that patients with a heart rate > 80 bpm before initiating weaning from nippv were more likely to have weaning failure. this finding is because cardiac dysfunction is the source of acute cardiogenic pulmonary edema (1). as a result, an increased heart rate may cause aberrant cardiac function (15). additionally, there is evidence that the presence of pneumonia leads to the failure of weaning from nippv because pneumonia impairs the correction of desaturation (19). this is particularly challenging in individuals who have acute cardiogenic pulmonary disease. no arterial blood gas risk indicators for weaning failure of nippv were identified in this study. other studies have shown that decreased acidosis enhanced the success rate of nippv (15, 20, 21). when dyspnea is decreased, the majority of patients respond to therapy. additionally, this study’s sample size may have been insufficient, which could have resulted in not finding a significant difference. momii et al. recommended a protocol for weaning, which included gradually modifying the ventilator mode and decreasing positive pressure every 30 minutes. the median duration of nippv was 8 hours, and the interquartile range was 0, which improved the success rate in weaning from nippv (22). positive pressure reduction data were not collected during nippv use in our study. there was no procedure for weaning from nippv, and the time to ventilator use or the ventilator mode (bipap or continuous positive airway pressure (cpap)) before opting to wean from nippv was not associated with the incidence of weaning failure from nippv. 5. limitations this study has some limitations. this study was conducted at a university-affiliated super tertiary care hospital in bangkok. therefore, the patients’ baseline prognostic factors may differ from those at other institutions. additionally, weaning from nippv was required in the ed owing to restricted resources. before applying these findings to a different situation, other hospital risk ratings (external validation) should be evaluated to determine whether predictive scores are reliable in predicting weaning from nippv in patients with acute cardiogenic pulmonary edema. furthermore, this was a retrospective study. some data were missing or incomplete, which resulted in incomplete data collection. 6. conclusion in patients with acute cardiogenic pulmonary edema under the nippv, weaning is associated with a significantly increased risk of failure in ages >75, presence of pneumonia, heart rate > 80 bpm before weaning, and urinary output < 150 cc/h during ventilation. based on the model designed in this study, patients with score ≤ 3.5 points, 4–5 points, and > 5 had low, moderate, and severe risk of weaning failure, respectively. weaning of high-risk patients should be postponed until their clinical prediction score shows a moderate or low risk or they should be closely observed after weaning. 7. declarations 7.1. acknowledgments we thank ellen knapp, phd, from edanz group (www.edanzediting.com/ac), for editing a draft of this manuscript. 7.2. authors’ contributions all authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e79 7.3. ethical considerations this study was approved by the faculty of medicine, committee on human rights related to research involving human subjects, ramathibodi hospital, mahidol university (coa. no mura2020/972). the ethics committee waived obtaining consent for this research as the patients’ medical records were used for data gathering and a statement covering patient data confidentiality and compliance with the declaration of helsinki was provided. 7.4. availability of data and material the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. 7.5. funding source no funding was obtained for this study. 7.6. competing interests the authors declare that they have no competing interests. references 1. collins sp, mielniczuk lm, whittingham ha, boseley me, schramm dr, storrow ab. the use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: a systematic review. ann emerg med. 2006;48(3):260-9. e4. 2. nava s, carbone g, dibattista n, bellone a, baiardi p, cosentini r, et al. noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. am j respir crit care med. 2003;168(12):1432-7. 3. masip j, peacock wf, price s, cullen l, martin-sanchez fj, seferovic p, et al. indications and practical approach to non-invasive ventilation in acute heart failure. eur heart j. 2018;39(1):17-25. 4. weng c-l, zhao y-t, liu q-h, fu c-j, sun f, ma y-l, et al. meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema. ann intern med. 2010;152(9):590-600. 5. rochwerg b, brochard l, elliott mw, hess d, hill ns, nava s, et al. official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure. eur respir j. 2017;50(2):1602426. 6. vital fm, ladeira mt, atallah án. non-invasive positive pressure ventilation (cpap or bilevel nppv ) for cardiogenic pulmonary oedema. cochrane database syst rev. 2013(5):cd005351. 7. felker gm, adams jr kf, konstam ma, o’connor cm, gheorghiade m. the problem of decompensated heart failure: nomenclature, classification, and risk stratification. am heart j. 2003;145(2 suppl):s18-s25. 8. adam ct, vieira ct, aguiar sdc, bündchen d, vieira dsr. [non-invasive mechanical ventilation weaning protocols: a systematic review]. fisioter pesqui. 2017;24(4):453-60. [portuguese]. 9. gray a, goodacre s, newby de, masson m, sampson f, nicholl j. noninvasive ventilation in acute cardiogenic pulmonary edema. n engl j med. 2008;359(2):142-51. 10. grace mp, greenbaum dm. cardiac performance in response to peep in patients with cardiac dysfunction. crit care med. 1982;10(6):358-60. 11. dobbe l, rahman r, elmassry m, paz p, nugent k. cardiogenic pulmonary edema. am j med sci. 2019;358(6):389-97. 12. nava s, hill n. non-invasive ventilation in acute respiratory failure. lancet. 2009;374(9685):250-9. 13. mckee pa, castelli wp, mcnamara pm, kannel wb. the natural history of congestive heart failure: the framingham study. n engl j med. 1971;285(26):1441-6. 14. members: atf, mcdonagh ta, metra m, adamo m, gardner rs, baumbach a, et al. 2021 esc guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc). with the special contribution of the heart failure association (hfa) of the esc. eur j heart fail. 2022;24(1):4-131. 15. duan j, han x, bai l, zhou l, huang s. assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients. intensive care med. 2017;43(2):1929. 16. roffi m, patrono c, collet jp, mueller c, valgimigli m, andreotti f, et al. 2015 esc guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the european society of cardiology (esc). eur heart j. 2016;37(3):267-315. 17. felker gm, lee kl, bull da, redfield mm, stevenson lw, goldsmith sr, et al. diuretic strategies in patients with acute decompensated heart failure. n engl j med. 2011;364(9):797-805. 18. mcdonagh ta, metra m, adamo m, gardner rs, baumbach a, böhm m, et al. 2021 esc guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc) with the special contribution of the heart failure association (hfa) of the esc. eur heart j. 2021;42(36):3599-726. 19. lemyze m, taufour p, duhamel a, temime j, nigeon o, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. leela-amornsin et al. 10 vangrunderbeeck n, et al. determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure. plos one. 2014;9(5):e97563. 20. singh v, khanna p, rao b, sharma s, gupta r. outcome predictors for non-invasive positive pressure ventilation in acute respiratory failure. j assoc physicians india. 2006;54:361-5. 21. liengswangwong w, yuksen c, thepkong t, nakasint p, jenpanitpong c. early detection of non-invasive ventilation failure among acute respiratory failure patients in the emergency department. bmc emerg med. 2020;20(1):80. 22. momii h, tashima y, kadokami t, narita s, yoshida m, ando s-i. experience of step-wise protocol using noninvasive positive pressure ventilation for treating cardiogenic pulmonary edema. eur j emerg med. 2012;19(4):267-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2016; 4 (3): 114-115 ev i d e n c e ba s e me d i c i n e evolution of fagan’s nomogram; a commentary abdelrahman ibrahim abushouk1∗ 1. faculty of medicine, ain shams university, cairo, egypt. received: february 2016; accepted: february 2016 cite this article as: ibrahim abushouk a.evolution of fagan’s nomogram; a commentary. emergency. 2016; nn(i):114-115. dear editor i read with interest your paper entitled “pre and post-test probabilities and fagan’s nomogram” (1). i would like to add a note concerning an update on fagan’s nomogram. generally, the basic idea of most nomograms is having the scales of 3 variables in a manner that if you draw a straight line between 2 values, the 3rd value is found where the line intersects the 3rd scale (2). they were initially developed in the 1980s by maurice d’ocange. nomograms remained popular in medical practice until the invention of pocket calculators and computers. their use increased again with the introduction of evidence-based medicine in clinical practice. in a letter to the new england journal of medicine in july 1975, dr terry fagan displayed a test characterization tool that went on to carry his name as the fagan’s nomogram (3). this nomogram is a simple application of the bayes’ theorem, which establishes a rule to calculate the post-test probability of a disease. however, fagan’s nomogram had a set of drawbacks that limited its use in clinical practice. these drawbacks included: 1the original bayes’ theorem is designed to deal with odds ratios, not probabilities, so algebraic conversion is needed to calculate probability. 2most diagnostic tests are characterized in terms of sensitivity & specificity in the literature, which need special equations to be converted into likelihood ratios (4). noticing these difficulties, in 2011, a group of researchers published a modern version of the nomogram that they named “bayes’ theorem nomogram”. the new nomogram targeted the former problems using: aparallel lines for probability and odds on each side of the nomogram figure. bthe inner lip along the entire circle contains values for sensitivity and specificity that can be connected to calculate the likelihood ratio of a certain diagnostic test (5). as illustrated in figure (a), a pretest probability of 18% and a likelihood ratio (lr+) of 2.8 for a diagnostic test would give a posttest probability of 38%. further advantages of the modern nomogram include: in rare ∗corresponding author: abdelrahman ibrahim abushouk; ain shams university, cairo, egypt. e-mail: abdelrahman.abushouk@med.asu.edu.eg . figure 1: the modern bayes’ theorem nomogram with an example of probability calculation as shown by the green line. disorders, having a very low pretest probability implies performing a diagnostic test with a fairly high lr (+). in fagan’s nomogram, the high values of lr are compressed in a tight portion over that scale (4), while in this model; a more spaced representation of high lr is feasible. replacing the linear form with a circular one works better for complex diagnostic protocols where addition of multiple arrows for different diagnostic tests may be required (5). considering the mentioned superiorities of the bayes’ theorem nomogram over the conventional fagan’s nomogram, it is highly recommended for clinicians to use it in conducting diagnostic protocols and formulating therapeutic plans. references 1. safari s, baratloo a, elfil m, negida a. part 4: pre and post test probabilities and fagan’s nomogram. emergencyan academic emergency medicine journal. 2016;4. 2. thimbleby h, williams d, editors. using nomograms to reduce harm from clinical calculations. healthcare inforthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 115 emergency. 2016; 4 (3): 114-115 matics (ichi), 2013 ieee international conference on; 2013: ieee. 3. fagan tj. letter: nomogram for bayes theorem. the new england journal of medicine. 1975;293(5):257-. 4. miettinen os, caro jj. foundations of medical diagnosis: what actually are the parameters involved in bayes’ theorem? statistics in medicine. 1994;13(3):201-9. 5. marasco j, doerfler r, roschier l. doc, what are my chances. umap journal. 2011;32:279-98. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references archives of academic emergency medicine. 2023; 11(1): e59 or i g i n a l re s e a rc h comparing ultrasonography and surface landmarkguided lumbar puncture in patients with obesity and difficult anatomy; a randomized controlled trial pitsucha sanguanwit1, phantakan tansuwannarat2,3, chinnarat bua-ngam4, supakrid suttabuth5, pongsakorn atiksawedparit2, satariya trakulsrichai1,3∗ 1. department of emergency medicine, faculty of medicine ramathibodi hospital, mahidol university, bangkok, thailand. 2. chakri naruebodindra medical institute, faculty of medicine ramathibodi hospital, mahidol university, samut prakan, thailand. 3. ramathibodi poison center, faculty of medicine ramathibodi hospital, mahidol university, bangkok, thailand. 4. department of diagnostic and therapeutic radiology, faculty of medicine ramathibodi hospital, mahidol university, bangkok, thailand. 5. department of emergency, bumrungrad international hospital, bangkok, thailand. received: june 2023; accepted: july 2023; published online: 21 august 2023 abstract: introduction: previous studies have shown higher lumbar puncture (lp) success rates when using ultrasound guidance. this study aimed to compare the first-attempt success rate of ultrasound-guided lp with blind technique of needle insertion using the palpable spinal surface landmark in patients with obesity or a difficult anatomy. methods: this prospective randomized controlled study was performed at the emergency department of ramathibodi hospital, an academic tertiary university hospital, from august 2015 to july 2016. results: 40 patients were enrolled (20 surface landmark-guided and 20 ultrasound-guided lps). 52.5% of the patients were male with the mean age of 60.33 ± 4.24 years. the first-attempt success rate in the ultrasound-guided lp group was significantly higher than the landmarkguided lp group (80% vs. 35%, respectively), with risk difference (rd) of 45.00% (95% confidence interval (ci): 17.72%, 72.28%). this indicated absolute risk reduction and number needed to treat of 45.00% and 2.22, respectively. the median procedural duration required to achieve successful lp in the ultrasound-guided lp group was significantly shorter than the surface landmark-guided lp group (5 [iqr: 3–18] minutes vs. 13.5 [iqr: 5-30] minutes, respectively). traumatic puncture as a complication occurred less frequently in the ultrasound-guided lp group than the surface landmarkguided lp group with risk ratio (rr) = 0.33 (95% ci: 0.08, 1.46) and rd = -20.00% (95% ci: -44.00%, 4.00%). this indicated absolute risk reduction and number needed to harm of 20.00% and 5.00, respectively. however, the difference was not significant. conclusion: using ultrasound to help localize the insertion point before lp increased the first-attempt success rate and improved other lp outcomes in thai patients with obesity or a difficult anatomy. it also shortened the procedural duration and reduced the incidence of traumatic tap. keywords: spinal puncture; ultrasonography, interventional; obesity; emergency service, hospital cite this article as: sanguanwit p, tansuwannarat p, bua-ngam c, suttabuth s, atiksawedparit p, trakulsrichai s. comparing ultrasonography and surface landmark-guided lumbar puncture in patients with obesity and difficult anatomy; a randomized controlled trial. arch acad emerg med. 2023; 11(1): e59. https://doi.org/10.22037/aaem.v11i1.2026. 1. introduction lumbar puncture (lp) is an important procedure that is commonly performed in the emergency department to evaluate and help diagnose several emergency or life-threatening con∗corresponding author: satariya trakulsrichai; department of emergency medicine, faculty of medicine ramathibodi hospital, mahidol university, rama vi road, bangkok 10400, thailand. tel: +66-2-2011084, fax: +66-22011086, email: satariya.tra@mahidol.ac.th; satariyatrakulsrichai@gmail.com, orcid: https://orcid.org/0000-0002-8313-026x. ditions, such as meningitis or subarachnoid hemorrhage (1, 2). lp can be performed on patients in different positions, including the lateral recumbent, prone, and upright positions (3). conventional lp involves palpation of certain anatomical landmarks, including the top of the iliac crest, which lies parallel to the l4 spinous process and is the most important bony landmark for lp. the l4 spinous process is located at the intersection of tuffier’s line or the line between the top of the iliac crest and the midline of the lumbar spine. then, the lumbar spinous processes of l3, l4, and l5, and the inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index p. sanguanwit et al. 2 terspaces between them, can be palpated. the spinal needle can be inserted into the subarachnoid space at the l3–l4 or l4–l5 interspace (1-3). several factors can impede the success of lp, including operator dependency and patient factors (4-7). palpable surface landmarks may be absent, indistinct, or distorted because of obesity, deformity, or degenerative changes associated with aging (4, 5). a previous study indicated that one of the major factors impeding the success of lp is body mass index (bmi) (4). specifically, in patients with a bmi of more than 35 kg/m2, the success rate of lp decreased (4). patients with obesity have a thick layer of subcutaneous fat, which makes the bony marker unclear, and thus precisely locating the site of lp needle insertion is difficult. abnormalities in the spinal column, such as ankylosing spondylitis or abnormalities after spinal surgery, also increase the likelihood of unsuccessful lp (5). therefore, performing lp in patients with surface landmarks that are difficult to palpate and in patients with anatomical alterations in the lumbar spine is challenging. if an lp attempt is unsuccessful, the next step is to perform lp under fluoroscopic guidance, especially in neonates and infants (8-10). ultrasound is a non-invasive and radiation-free imaging approach. ultrasound imaging for assisting lp has been used for many years (11). pre-procedural ultrasound imaging is used to locate the intervertebral space, obtain additional anatomical information, and permit more accurate estimation of needle depth and direction (12, 13). reducing the number of lp attempts using ultrasound guidance is also desirable because multiple attempts at needle insertion are associated with complications, such as hematoma, spinal nerve damage, and infection (13). previous studies have shown higher lp success rates when using ultrasound guidance and when the technique is performed by emergency medicine physicians or anesthesiologists, especially in patients with obesity and patients with a difficult anatomy (9, 13-21). however, even though the utility of ultrasound guidance for lp has shown concrete results in some studies, other studies have demonstrated opposite outcomes, such as no difference in the success rate or the number of total attempts (22-27), which do not support routine use of ultrasound guidance for lp. the overall procedural duration of lp is of concern to many physicians in clinical practice. some studies have shown benefits with ultrasound guidance in terms of the procedural duration (15, 28, 29); however, other studies have shown no difference in the total procedural duration (16, 17, 22, 26). moreover, other studies have reported that the use of ultrasound increases the overall procedural duration because of the increased scanning duration (14, 21). the aim of the present study was to compare the firstattempt success rate of ultrasound-guided lp with the standard blind technique of needle insertion using palpable spinal surface landmarks in patients with obesity or a difficult anatomy. we also compared the overall success rate, procedural duration, and complications between the two methods. 2. methods 2.1. study design and setting this prospective randomized controlled study was performed at the emergency department of ramathibodi hospital, mahidol university, bangkok, thailand, which is an academic tertiary university hospital that is staffed with medical students, nurses, residents, and attending physicians. the study was performed in accordance with the consort guidelines. the primary objective of the study was to compare the firstattempt success rate between the two groups. the secondary objectives of the study were to analyze the overall success rate (defined as success within three attempts), compare the procedural duration (the time from needle insertion to obtaining cerebrospinal fluid), and compare immediate complications (including traumatic tap, local infection, hematoma, spinal cord or nerve root injury, and brain herniation) between the two groups. the study protocol was approved by the ethics committee of ramathibodi hospital (id 04-58-03), and written informed consent was obtained from all patients. this trial was retrospectively registered in the thai clinical trial registry at clinicaltrials.gov, identification number tctr20200716007 (2020-07-16). 2.2. study population adult patients aged >18 years who underwent lp for any clinical indication at the emergency department and who had difficult lp criteria (bmi of >25 kg/m2, which is defined as obesity in the thai population (30); previous lumbar spine surgery; or scoliosis) were included. the exclusion criteria included pregnancy, unstable vital signs, signs of an increase in intracranial pressure, skin infection in the area of lp, or bleeding tendency (e.g., coagulopathy). 2.3. study protocol and interventions the participating physicians included two 3rd year emergency residents and two emergency medicine attending staff members. all of the lp procedures were performed by these participating physicians, all of whom were certified to perform this procedure and had completed the ultrasound-guided lp training course. one of the authors (c.b.), who is an interventional radiologist and expert in ultrasound-guided procedures, delivered the ultrasoundguided lp training course to the participating physicians. the four physicians passed the training course, which inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e59 volved a standardized 120-minute teaching module to perform ultrasound-guided lp. this teaching module consisted of a 20-minute lecture describing the use of the ultrasound machine, a 10-minute video about ultrasound-guided lp, an 80-minute ultrasound guidance simulation session to localize the lp insertion point, and 10 minutes of questions at the end. after finishing the module, all four physicians were required to attend a hands-on workshop and take a picture of the lp needle insertion point in 10 patients, with subsequent approval from the radiologist. when the four physicians had finished the training module and had correctly collected 10 pictures of the lp needle insertion point, they were considered to have passed and were eligible for involvement in the study. randomization was performed using computer-generated random numbers. block randomization was done with the block size of 4. allocation concealment was achieved using the sequentially numbered opaque sealed envelopes (snose) technique. the patients were enrolled by an emergency physician who served as the primary physician. the participating physicians were assigned the patients for intervention. the patients were randomly divided into two groups: the surface landmark-guided lp group and the ultrasound-guided lp group. the group allocation was concealed using sealed opaque envelopes, which were opened by the participating physicians who would perform the lp procedure before performing the intervention. due to the nature of the study, blinding of the physicians who performed the procedure was not possible. all patients were unaware of which method of lp would be performed on them. the person who analyzed the outcomes was also blinded to which approach was used. the ultrasound machine used in this study was the ge logiq e portable ultrasound machine with the linear probe (12lrs). standard monitoring and intravenous access were established in all patients. the patients were recruited after the study was approved by the ethics committee. the period of recruitment was 1 year. the baseline characteristics of the patients were recorded, including age, sex, weight, height, bmi, underlying diseases, previous spinal surgery, history of brain computed tomography, and indication for lp. all of the patients were positioned in the left lateral decubitus position, and the back was placed next to the edge of the bed. then, the patient’s chin was set near to the chest, and the knees were bent toward the chest. in both groups, the physicians palpated the iliac crest, lumbar spinous processes, and interspinous spaces for landmark identification. additional ultrasonography of the lumbar area was performed in the group that underwent ultrasoundguided lp to examine the spinal anatomy. 2.4. ultrasonography the ultrasound transducer was first placed in the transverse position to identify the spinous processes in the center of the image. the spinous processes were seen as distinct hyperechoic peaks with posterior acoustic shadows (figure 1) (11, 19). the ultrasound transducer was slowly moved superiorly until the next upper spinous process was identified. subsequently, the transducer was rotated 90° clockwise to align the ultrasound orientation longitudinally over the midline. from this view, the two previously identified spinous processes were indicated as two crescent-shaped, concave, hyperechoic structures with posterior acoustic shadows. the space between these two spinous processes represented the intervertebral space and was marked on the middle of the probe (figure 1). the ultrasound images were collected and recorded in each patient’s record, and the images recorded were checked and confirmed as correct by the radiologist. follow-up assessments were performed after the procedure following the routine hospital protocol. we observed the patients until 24 hours after lp. 2.5. outcomes the primary outcome was the first-attempt success rate of lp procedure. any additional needle attempt was defined as complete withdrawal of the introducer needle from the skin and subsequent reinsertion. lp success was observed and recorded by the lp operator and investigator. the secondary outcomes were the overall success rates, the procedural durations, and immediate complications. patients who underwent more than three lp attempts were excluded from the analyses of procedural duration and complications. 2.6. definitions a successful attempt was defined as obtaining sufficient cerebrospinal fluid for analysis. traumatic tap was defined as a decrease in the erythrocyte count between the first and last tubes of at least 25%, together with an absolute erythrocyte count of <400 erythrocytes/µl in tube 3 or tube 4 (31). 2.7. statistical analysis the sample size was calculated using spss software (version 18) based on the results of a previous study on patients with difficult lp criteria (14), which demonstrated first-attempt success rates of 100% and 42.5% in the ultrasound-guided lp group and the surface landmark-guided lp group, respectively. accepting an alpha error of 5% and a beta error of 20% (80% power), a total of 34 patients were required, which were then divided into two groups (at least 17 patients per group were required). for describing data, normally distributed continuous data were presented as mean ± standard deviation; otherwise, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index p. sanguanwit et al. 4 the data were presented as median with interquartile range. categorical data were presented as frequency and percentage. intention to treat was applied for final analysis. comparisons between groups were made using the student’s ttest if two independent continuous datasets were normally distributed; otherwise, the groups were analyzed using the mann–whitney u test. differences in categorical variables were evaluated using the chi-square test or fisher’s exact test, as appropriate. in addition, risk difference (rd) and risk ratio (rr) and their 95% confidence interval (ci) were also estimated. a p value of <0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of studied cases a total of 40 patients were enrolled in the study. all of the patients underwent computed tomography, and no patients were lost to follow-up (figure 2). twenty patients underwent surface landmark-guided lp, while the other 20 patients underwent ultrasound-guided lp. most of the patients were male (52.5%), and the mean age of the patients was 60.33 ± 4.24 (range: 18 – 89) years. the mean bmi, mean weight, mean age, percentage of patients with underlying disease, and the indications for lp were not significantly different between the two groups (table 1). 3.2. comparing the outcomes between groups table 2 shows the primary and secondary outcomes of the study. the first-attempt success rate in the ultrasoundguided lp group was significantly higher than the landmarkguided lp group (80% vs. 35%, respectively), with rd of 45.00% (95% ci: 17.72%, 72.28%). this indicated absolute risk reduction and number needed to treat of 45.00% and 2.22, respectively. in addition, rr was 2.29 (95% ci: 1.21, 4.32). every patient achieved successful lp within three attempts; therefore, the overall successful rate was 100% in both groups. the median procedural duration required to achieve successful lp in the ultrasound-guided lp group was significantly shorter than in the surface landmark-guided lp group (5 [iqr: 3–18] minutes vs. 13.5 [iqr: 5-30] minutes, respectively). traumatic puncture as a complication occurred less frequently in the ultrasound-guided lp group than the surface landmark-guided lp group with rr = 0.33 (95% ci: 0.08, 1.46) and rd = -20.00% (95% ci: -44.00%, 4.00%). this indicated absolute risk reduction and number needed to harm of 20.00% and 5.00, respectively. however, the difference was not significant. the other complications were monitored and observed until 24 hours after lp following the routine hospital protocol. no other complications were reported in any of the patients. 4. discussion this randomized controlled study included 40 patients with obesity or a difficult anatomy. we demonstrated that ultrasound-guided lp significantly increased the firstattempt success rate and reduced the procedural lp duration in thai patients with obesity or a difficult anatomy when compared with conventional surface landmark-guided lp. our study supports the findings of other studies showing that ultrasound improves the success of lp in patients with a difficult anatomy (11, 17, 20, 27) and in patients classified as overweight or obese, especially in the emergency setting (16, 27, 28). we used a lower bmi than some studies that used a bmi of >28–35 kg/m2 (14, 16, 28). one study used a bmi of >25 kg/m2, which is similar to our study; however, the patients were of a different ethnicity. the bmi in that study was considered to be overweight; however, in thai people, a bmi of >25 kg/m2 is considered as obesity. one study performed in emergency department shows that ultrasound-guided lp improves success rates and decreases lp time in obese patients with difficulty in the lp. this study was performed in chinese adult obese patients; however, bmi >28 kg/m2 was used as the obesity diagnostic criteria. our study also supported previous observations showing that less experienced operators, such as residents, could perform lp with ultrasound assistance (27, 29). we also found that the procedural duration was shorter in the ultrasound-guided lp group; however, we did not evaluate the time taken for landmark identification, and thus the total length of the procedure in the ultrasound-guided lp group may not necessarily have been shorter than in the surface landmark-guided lp group. this was the case in previous studies showing that although the performance time was shorter, the landmark identification time was longer, so the total procedural duration was longer (14, 21, 32). however, a shorter procedural duration might provide some advantages or improve patient satisfaction by decreasing the duration of uncomfortable positioning for the patient during lp. the shorter procedural duration might also infer that ultrasound guidance could identify the needle site more precisely than the conventional surface landmark-guided lp method. in terms of complications, although no statistically significant differences were observed between the two groups, the ultrasound-guided lp group demonstrated a lower incidence of traumatic tap than the surface landmark-guided lp group. similar to previous studies, the number of cases of traumatic lp was significantly lower in the ultrasound-guided lp group (2, 4, 5, 11). on the basis of our findings, we believe that the use of ultrasound to guide lp in adult patients should be considered to increase the procedural success rate and reduce the number this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e59 of needle insertion attempts, especially in patients with obesity or those with anatomical landmarks that are difficult to palpate. 5. limitation the main limitation of this study was that lp procedure and the ultrasound are operator-dependent procedures that require experience and skill to perform effectively. although a standard educational workshop was held to train the participating physicians, the four physicians may have had different levels of skill in performing ultrasound-guided lp. this limitation could potentially impact the generalizability and precision of the study’s results, given the variations in levels of experience and procedural skills among the participants. however, when physicians have received prior training on ultrasound-guided lp, the utilization of ultrasound-guided lp may present an alternative approach to enhance the initial success rate of lp in cases involving obesity and difficult anatomy. another limitation was the lack of blinding regarding the technique used, which could introduce information bias for the participating physicians who performed the procedure. however, the analyst who analyzed the outcomes remained blind to the intervention arms. 6. conclusion our study provides support for the benefits of ultrasoundguided lp in specific patient populations, particularly those with challenging anatomical landmarks that are difficult to identify through manual palpation. in this study, ultrasoundguided lp was associated with an increased rate of success on the first attempt, decreased procedural duration, and a lower incidence of traumatic tap. furthermore, the use of ultrasound guidance has the potential to enhance physician confidence, improve patient safety, and optimize the diagnostic yield, making it a valuable option for challenging lp cases. 7. declarations 7.1. acknowledgments the authors express sincere thanks to umaporn udomsubpayakul, department of clinical epidemiology and biostatistics, faculty of medicine ramathibodi hospital, mahidol university, for her help with statistical analysis. we wish to acknowledge the contributions of all of the medical and nursing staff from the emergency department of ramathibodi hospital for their collaboration. we thank emily woodhouse, phd, from edanz (www.edanz.com/ac) for editing a draft of this manuscript. this study was presented as poster presentation in 37th isicem: international symposium on intensive care & emergency medicine, brussels, belgium. 7.2. competing interests the authors declare that they have no competing interests. 7.3. consent for publication not applicable. 7.4. funding and support no funding was received for this study. 7.5. authors’ contribution ps, pt, and cb designed the study and developed the protocol. pt, ss, and cb were responsible for data collection. ps, pt, pa, and st were responsible for data analysis. ps, pt, and st wrote the manuscript. ps, and st provided final approval of this version to be published. ps and st agree to be accountable for all aspects of the work. all authors read and approved the final manuscript. 7.6. data availability the data are not available for public access because of patient privacy concerns, but they are available from the corresponding author upon reasonable request. 7.7. ethics approval and informed consent this study was approved by the ethics committee of the faculty of medicine, ramathibodi hospital, mahidol university (id 04-58-03, mura2015/217). all methods were carried out in accordance with relevant guidelines and regulations, such as the declaration of helsinki, the belmont report, cioms guidelines, and the international conference on harmonization in good clinical practice (ich-gcp). informed consent was obtained from all participants/patients. 7.8. using artificial intelligence chatbots the authors declare that they did not use artificial intelligence chatbots. references 1. jurado r, walker hk. cerebrospinal fluid. in: walker hk, 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2021;53(1):9-14. 21. wang q, yin c, wang tl. ultrasound facilitates identification of combined spinal-epidural puncture in obese parturients. chin med j (engl). 2012;125(21):3840-3. 22. evans dp, tozer j, joyce m, vitto mj. comparison of ultrasound-guided and landmark-based lumbar punctures in inexperienced resident physicians. j ultrasound med. 2019;38(3):613-20. 23. grady m, runyon m, weekes a, hogg m, chaudoin l. comparison of ultrasound-marked versus standard lumbar puncture success in infants. pediatr emerg care. 2022;38(1):e121-e5. 24. halkur shankar s, biswas s, kumar a, gupta a, goel a, khan ma, et al. role of routine use of ultrasonographic guidance for performing lumbar punctures. postgrad med j. 2021;97(1143):23-8. 25. hayes j, borges b, armstrong d, srinivasan i. accuracy of manual palpation vs ultrasound for identifying the l3-l4 intervertebral space level in children. paediatr anaesth. 2014;24(5):510-5. 26. peterson ma, pisupati d, heyming tw, abele ja, lewis rj. ultrasound for routine lumbar puncture. acad emerg med. 2014;21(2):130-6. 27. rizk ms, zeeni ca, bouez jn, bteich nj, sayyid sk, alfahel ws, et al. preprocedural ultrasound versus landmark techniques for spinal anesthesia performed by novice residents in elderly: a randomized controlled trial. bmc anesthesiol. 2019;19(1):208. 28. li l, tao w, cai x. ultrasound-guided vs. landmarkguided lumbar puncture for obese patients in emergency department. front surg. 2022;9:874143. 29. li y, carandang ra, ade s, flahive j, daniello k. ultrasound-guided lumbar puncture improves success rate and efficiency in overweight patients. neurol clin pract. 2020;10(4):307-13. 30. world health organization, regional office for the western pacific. the asia-pacific perspective: redefining obesity and its treatment. sydney: health communications australia; 2000. available from: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e59 https://apps.who.int/iris/handle/10665/206936 31. euerle bd. spinal puncture and cerebrospinal fluid examination. in: roberts jr cc, thomsen tw, editor. roberts and hedges’ clinical procedures in emergency medicine and acute care. 7th ed. philadelphia: elsevier; 2019. p. 1258–80. 32. park sk, yoo s, kim wh, lim yj, bahk jh, kim jt. ultrasound-assisted vs. landmark-guided paramedian spinal anaesthesia in the elderly: a randomised controlled trial. eur j anaesthesiol. 2019;36(10):763-71. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index p. sanguanwit et al. 8 table 1: comparing the baseline characteristics of studied cases between groups characteristics lumbar puncture guided with p value ultrasound (n = 20) surface landmark (n = 20) gender male 9 (45.0) 12 (60.0) 0.342 female 11 (55.0) 8 (40.0) age (years) mean ± sd 66.1 ± 18.76 54.55 ± 18.59 0.058 anthropometry weight (kg) 67.45 ± 9.62 69.55 ± 6.28 0.419 height (cm) 157.45 ± 7.3 158.95 ± 6.61 0.500 body mass index (kg/m2 ) 27.14 ± 1.95 27.48 ± 1.11 0.497 underlying disease (%) yes 14 (70.0) 17 (85.0) 0.451 no 6 (30.0) 3 (15.0) indications (%) central nervous system infection 18 (90.0) 15 (75.0) 0.408 headache 0 (0.0) 1 (5.0) 1.00 others 2 (10.0) 4 (20.0) 0.661 data are presented as mean ± standard deviation (sd) or frequency (%). table 2: comparing the outcomes between ultrasound-guided lumbar puncture and surface landmark-guided lumbar puncture parameters lumbar puncture guided with p value ultrasound (n = 20) surface landmark (n = 20) the first-attempt success rate number (%) 16 (80.0) 7 (35.0) 0.009 the procedural duration (minutes) median (range) 5 (3–18) 13.5 (5–30) 0.002 traumatic tap number (%) 2 (10.0) 6 (30.0) 0.235 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e59 figure 1: cross-sectional view of the ultrasound showing a hyperechoic peak with a posterior acoustic shadow from the spinous process in the midline and transverse processes on both sides (a); longitudinal view of the ultrasound showing two spinous processes in the craniocaudal orientation and the intervertebral space at the center (b). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index p. sanguanwit et al. 10 figure 2: study flow diagram. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e19 rev i ew art i c l e monkeypox disease with a focus on the 2022 outbreak; a narrative review zohreh tehranchinia1, reza m robati1∗, hamideh moravvej1, mojtaba memariani1, hamed memariani1 1. skin research center, shahid beheshti university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 16 january 2023 abstract: monkeypox is a zoonotic disease caused by a double-stranded dna virus belonging to the genus orthopoxvirus. despite being endemic in central and west africa, the disease has received relatively little research attention until recent times. as the coronavirus disease 2019 (covid-19) pandemic continues to affect the world, the rising number of monkeypox cases in non-endemic countries has further stoked global public health concerns about another pandemic. unlike previous outbreaks outside africa, most patients in the present outbreak had no history of travel to the endemic regions. the overwhelming majority of patients were initially identified amongst homosexual men, who had attended large gatherings. mutations in the coding regions of the viral genome may have resulted in fitness adaptation, enhancement of immune evasion mechanisms, and more efficient transmissibility of the 2022 monkeypox virus. multiple factors such as diminished cross-protective herd immunity (cessation of smallpox vaccination), deforestation, civil war, refugee displacement, farming, enhanced global interconnectedness, and even climate change may facilitate the unexpected emergence of the disease. in light of the increasing number of cases reported in the present outbreak, healthcare professionals should update their knowledge about monkeypox disease, including its diagnosis, prevention, and clinical management. herein, we provide an overview of monkeypox, with a focus on the 2022 outbreak, to serve as a primer for clinical practitioners who may encounter the disease in their practice. keywords: monkeypox; disease outbreaks; diagnosis; vaccination; therapeutics cite this article as: tehranchinia z, robati rm, moravvej h, memariani m, memariani h. monkeypox disease with a focus on the 2022 outbreak; a narrative review. arch acad emerg med. 2023; 11(1): e19. https://doi.org/10.22037/aaem.v11i1.1856. 1. introduction as the coronavirus disease 2019 (covid-19) pandemic continues to rage, a second public health threat is lurking in the shadows: a global outbreak of monkeypox. emerging and re-emerging zoonotic diseases such as covid-19, monkeypox, ebola, and zika still levy an unmercifully heavy toll upon human health worldwide (1). as previously thought to be confined to africa, monkeypox is now causing a worldwide outbreak. the disease disproportionately has affected males who have had sex with males. in spite of being endemic in west and central africa, monkeypox has lately emerged in numerous non-endemic countries, evoking a great deal of concern. only few cases had been detected outside of africa prior to 2022. on 23 july 2022, the world health organization (who) declared monkeypox a public health emergency of international concern (2). currently, healthcare profession∗corresponding author: reza m robati; skin research center, shahid beheshti university of medical sciences, tehran, iran. tel: +982122741509, e-mail: rezarobati@sbmu.ac.ir; rmrobati@gmail.com. orcid: https://orcid.org/0000-0002-7947-8642. als are learning about the clinical presentations and treatment of monkeypox infection as public health agencies strive to contain the ongoing outbreak. due to a lack of control over the spread of monkeypox in endemic african countries, the disease is now spreading to nonendemic countries. the 2022 monkeypox outbreak outside of africa is currently the largest in history (3). given the fact that the number of confirmed cases in the present outbreak is on the rise, clinicians ought to extend their knowledge of this disease, including prevention, clinical management, prophylaxis, and basic infection control (4). furthermore, covid-19 and monkeypox may occur coincidentally, which should be taken into account. as a result, both or one of the diseases may experience changes related to infection pattern, severity, management, or response to vaccination. professionals need to update their knowledge of the monkeypox, including its prevention, clinical diagnosis, control, and management, to fully comprehend the consequences of the disease (5). in this paper, we intend to provide an overview of monkeypox virus infection with a focus on the 2022 outbreak. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index z. tehranchinia et al. 2 figure 1: a global map of confirmed monkeypox cases as of september 26, 2022. countries with confirmed cases are as follows: andorra (n = 4), argentina (n = 326), aruba (n = 3), australia (n = 135), austria (n = 307), bahamas (n = 2), bahrain (n = 1), barbados (n = 1), belgium (n = 757), benin (n = 3), bermuda (n = 1), bolivia (n = 164), bosnia and herzegovina (n = 3), brazil (n = 7300), bulgaria (n = 6), cameroon (n = 8), canada (n = 1389), central african republic (n = 8), chile (n = 783), china (n = 1), colombia (n = 1653), costa rica (n = 4), croatia (n = 29), cuba (n = 2), curaçao (n = 3), cyprus (n = 5), czechia (n = 66), democratic republic of the congo (n = 195), denmark (n = 183), dominican republic (n = 31), ecuador (n = 93), egypt (n = 1), el salvador (n = 4), estonia (n = 11), finland (n = 33), france (n = 3970), georgia (n = 2), germany (n = 3601), ghana (n = 84), gibraltar (n = 6), greece (n = 72), greenland (n = 2), guadeloupe (n = 1), guatemala (n = 18), guyana (n = 2), honduras (n = 6), hong kong (n = 1), hungary (n = 77), iceland (n = 12), india (n = 12), indonesia (n = 1), iran (n = 1), ireland (n = 178), israel (n = 250), italy (n = 842), jamaica (n = 14), japan (n = 4), jordan (n = 1), latvia (n = 5), lebanon (n = 11), liberia (n = 3), lithuania (n = 5), luxembourg (n = 55), malta (n = 33), martinique (n = 1), mexico (n = 1367), moldova (n = 2), monaco (n = 3), montenegro (n = 2), morocco (n = 3), netherlands (n = 1221), new caledonia (n = 1), new zealand (n = 9), nigeria (n = 277), norway (n = 91), panama (n = 13), paraguay (n = 1), peru (n = 2311), philippines (n = 4), poland (n = 173), portugal (n = 917), qatar (n = 5), republic of the congo (n = 5), romania (n = 39), russia (n = 2), saint martin (n = 1), saudi arabia (n = 8), serbia (n = 40), singapore (n = 19), slovakia (n = 14), slovenia (n = 46), south africa (n = 5), south korea (n = 2), spain (n = 7083), sudan (n = 7), sweden (n = 186), switzerland (n = 503), taiwan (n = 3), thailand (n = 8), turkey (n = 1), ukraine (n = 3), united arab emirates (n = 16), united kingdom (n = 3585), united states (n = 25161), uruguay (n = 6), venezuela (n = 5). [according to the data obtained from https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html]. 2. virology being an enveloped double-stranded dna virus, monkeypox virus belongs to orthopoxvirus genus of the poxviridae family. several different poxviruses have been proven to cause infections in human beings including, but not limited to, variola (smallpox), cowpox, monkeypox, vaccinia, and molluscum contagiosum virus (6). small mammals and rodents are the natural hosts of monkeypox virus. as a result of its wide spectrum of potential hosts, monkeypox virus circulates for long periods in the wild, while occasionally causing disease in humans by spillovers (7). monkeypox virus exhibits a brick-like structure of around 200 nm × 200 nm × 250 nm, with a genome size of approximately 197 kbp (8). while most of the genes encoded by the viral genome are not indispensable for multiplication in cell culture, they may bestow upon the virus the ability to defend against host immunity (4). virus replication takes place in the cytoplasm of infected cells through complex molecular pathways. at each end of the viral genome, there exist identical but oppositely oriented terminal reads of around 6 kbp, with a set of short tandem repeats and terminal hairpin loops. moreover, the monkeypox genome encompasses approximately 190 non-overlapping open reading frames of >180 bp in length, encompassing ≥60 amino acids (9). housekeeping genes, including those contributing to transcription, replication, and assembling virus particle, are all encoded by the central conserved region (8). as with other orthopoxviruses, the monkeypox dna has a low g/c content (about 31%) (9). monkeypox virus has been divided into at least two distinct genetic clades, clade 1 (the former congo basin or central african clade) and clade 2 (the former west african clade). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e19 geographic, clinical, genomic, and epidemiological characteristics also differ from clade to clade (10). genomic analyses indicate that a new strain is associated with the ongoing outbreak. this strain is diverged from clade 2 by almost 50 single nucleotide polymorphisms (snps) (11). in other words, the current circulating virus is phylogenetically close to clade 2, but it differs enough from clade 2 to be classified as clade 3. as opposed to clade 1, clade 2 exhibits reduced pathogenic characteristics and less transmissibility with lower case fatality rates (12). recent phylogenetic studies divulged that the 2022 outbreak cluster (lineage b1) diverged from the lineage a1 during microevolutionary changes following the virus exportation from nigeria to britain, israel, and singapore in 2017–2019 (11). 3. a brief history of monkeypox monkeypox is endemic to tropical rainforests in central and west african countries. the disease has received relatively little research attention in spite of being endemic in these regions. the monkeypox virus was first identified in the late 1950s in danish primate research facilities. later, a child in the democratic republic of congo (drc) became the first human case in 1970. since 1970s, there have been cases reported from 10 african countries (13). a detailed discussion of the previous outbreaks is beyond the scope of this paper. the epidemiology of these cases and outbreaks between 1970 and 2019 is summarized in a systematic review by bunge et al. (2022) (14). most cases occur sporadically or in connection with localized outbreaks. in the congo basin, nearly 30,000 cases of monkeypox, with a few hundred deaths, have been reported since the 1970s. in the 1980s, the most common source of infection was animal contact (72%), while human contact explained 78% of cases in the 1990s. before the 1990s, almost all deaths occurred in children under 10 years of age. since then, this rate has decreased to 35%. there is a possibility that this change may be due to the waning of cross-protective effects provided by previous smallpox vaccinations (15). transmission is thought to occur through inhalation of respiratory droplets, direct contact with skin lesions, exposure to contaminated body fluids (e.g. breastmilk, seminal fluid, blood, respiratory droplets), and even through contaminated fomites (16). monkeypox affects the drc more than any other country, and no other country has reported cases continuously over the past 50 years. cases outside of endemic countries are usually associated with international travel or importations of infected animals (14). as a result of the 2003 outbreak in the united states, linked to infected pet prairie dogs, the disease has grown to become a global public health concern. infected individuals became sick when they came into contact with pet prairie dogs that were initially kept with rodents imported from ghana in western africa (17). over the past few years, nigeria has been the source of several travelassociated monkeypox cases. in this respect, three cases were reported in the united kingdom (uk) in 2018 and 2019, one in israel (2018) and one in singapore (2019). there was a fourth case in the uk (2018) caused by nosocomial transmission (14). many different theories have been put forward as to why monkeypox cases have been on the rise in the last few decades. it seems that factors such as diminished cross-protective herd immunity (cessation of smallpox vaccination), deforestation, civil war, refugee displacement, farming, enhanced global interconnectedness, and even climate change contribute to these outbreaks (18). 4. the ongoing global outbreak there was a monkeypox case reported in the uk on 6th may 2022, a traveler who had recently returned from nigeria. since then, an increasing number of patients were identified in over 100 countries (figure 1) across the globe (19). as of september 26, 2022, more than 65900 confirmed cases were reported worldwide (figure 2a), 26 of whom succumbed to death (figure 2b). following reports of racist and stigmatizing language surrounding the name of the disease, the world health organization (who) has changed the name of monkeypox to mpox in november 2022 (20). unlike previous outbreaks outside africa, the majority of patients in the present outbreak had no travel history to the endemic countries. the disease is primarily observed among men who had sex with men attending large gathering events. it is speculated that an undetected chain of infections may have been responsible for the unpredictable resurgence of outbreaks across the globe (21). the outbreak dynamics are therefore complicated by this, which enlightens the need for urgent global surveillance. besides, non-synonymous mutations in the coding regions of the viral genome (e.g. b21 protein; an important antibody target with several key immunodominant epitopes) may have resulted in fitness adaptation, enhancement of immune evasion mechanisms, and more efficient transmissibility of the monkeypox virus (11). researchers also noticed that certain mutation patterns in the 2022 monkeypox viruses matched the types of mutations that apolipoprotein b mrna-editing catalytic polypeptide-like 3 (apobec3) enzymes would introduce (12). 5. clinical features and differential diagnosis although most cases of monkeypox are self-limited (lasting between 2 and 4 weeks), severe cases do occur, with a fatality rate of 3–10%. the median incubation period for monkeypox infection is usually 7 days (22). typically, the disease is this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index z. tehranchinia et al. 4 figure 2: cumulative number of confirmed cases (a) and deaths (b) related to the monkeypox as of september 26, 2022 [according to the data obtained from https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html]. figure 3: clinical symptoms of the 2022 monkeypox disease. [according to the data obtained from https://www.cdc.gov/poxvirus/monkeypox/response/2022/demographics.html]. associated with a febrile prodrome phase (characterized by fever, headache, malaise, fatigue, and lethargy), followed by a rash that may appear anywhere on the body (figure 3). the rash starts on the face and then spreads centrifugally to other parts of the body (23). the majority of them occur on the face and extremities, affecting palms, oral mucosa, genitals, and conjunctiva. the rash progresses through four morphological stages: macular, papular, vesicular, and pustular. at any given time, the lesions are in the same stage of progression (a useful characteristic for distinguishing chickenpox from this condition). pustules eventually form crusts that desquamate after a couple of weeks (22). that said, many homosexual men have reported painless anogenital lesions associated with the monkeypox during the present outbreak, often withthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e19 out a prodrome, after close contact with an infected individual (24). a bewildering array of infectious diseases can imitate the symptoms of monkeypox. in the early stages of the infection, the signs and symptoms are analogous to those of smallpox; however, unlike smallpox, lymphadenopathy is a prominent feature. lymphadenitis occurs primarily in sub-mental, submandibular, cervical, and inguinal regions. in clinical practice, genital sores could easily be mistaken for lesions caused by certain sexually-transmitted diseases including syphilis, genital herpes, chancre, and lymphogranuloma venereum (25). physicians should also be cognizant of co-infection with other viral diseases such as varicella-zoster or human immunodeficiency virus (hiv ). as a result of the monkeypox disease, complications such as secondary bacterial infections, sepsis, myocarditis, bronchopneumonia, encephalitis, sight-threatening keratitis may also occur (26). the risk of experiencing severe illness is higher in children, especially those who have eczema, pregnant women, and individuals who have immunocompromising conditions (27). the gold standard for its diagnosis is pcr assay of lesion specimens, and this is the first test that should be performed. fluid from vesicles and pustules, along with dried crusts, are the best diagnostic samples. additionally, a biopsy is an option when possible (28). viral dna may also be found in saliva, blood, urine, feces, and nasopharyngeal swabs (29). pcr amplification usually targets the conserved regions of extracellular envelope protein (b6r), dna polymerase e9l, dna-dependent rna polymerase subunit 18 (rpo18), and complement binding protein c3l, f3l, and n3r genes (30). specific confirmation of monkeypox cannot be achieved via antibody and antigen detection methods, because members of the orthopoxvirus are serologically cross-reactive. after 5 and 8 days of infection, monkeypox patients can be tested for igm and igg specific antibodies using enzyme-linked immunosorbent assay (elisa). however, these procedures are not recommended for diagnosis or case investigation when resources are limited (31). overall, serological tests are helpful in epidemiologic investigations, retrospective diagnosis of past infections, and diagnosis of late clinical manifestations (e.g. encephalitis). although serology tests may cross-react with a prior smallpox vaccination, unvaccinated individuals should not be concerned (4). 6. clinical management most monkeypox cases, particularly in the ongoing outbreak, are mild and self-limited. thus, supportive care usually suffices without any medical intervention (32). nevertheless, the prognosis is affected by a number of factors such as the initial clinical presentation, the presence of comorbidities, and the status of previous vaccinations. the main objective of supportive care is to maintain an adequate fluid balance. if necessary, other measures should be considered, including hemodynamic support, supplemental oxygen, and treatment of bacterial secondary infections (4). currently, there is no specific monkeypox treatment approved by the us food and drug administration (fda). nevertheless, several drugs including tecovirimat, brincidofovir, and cidofovir may be considered for anti-viral therapy in patients suffering from severe diseases (e.g. hemorrhagic disease, confluent lesions, sepsis, encephalitis, or other conditions requiring hospitalization) or in individuals who are at a high risk of severe diseases or complications (e.g. immunocompromised patients, children, people with severe skin conditions, and pregnant or breastfeeding women) (31, 33). the antiviral drug of choice is tecovirimat. the drug blocks the final maturation and release of virions by inhibiting the viral envelope protein vp37. brincidofovir, an analogue of the intravenous drug cidofovir, is a new medication for the treatment of human smallpox disease in adult and pediatric patients. it acts as a viral dna polymerase inhibitor (30). a prophylactic intravenous dose of vaccinia immune globulin (vigiv ) may also be beneficial for patients with severe monkeypox infections or individuals with t-cell immunodeficiency when smallpox vaccination is contraindicated (34). 7. prevention in order to prevent the infection, vaccination is the first line of defense (31). however, the high rates of adverse events associated with live, attenuated virus vaccination limit their general use, in spite of providing effective protection (31). post-exposure prophylaxis (vaccination following monkeypox exposure for those at risk) and pre-exposure prophylaxis (vaccination against monkeypox for those at high risk of exposure, such as laboratory workers performing monkeypox diagnostic testing) can be considered after a careful assessment of the risks and benefits (35). there are currently two smallpox vaccines licensed in the united states: acam2000® (emergent product development gaithersburg, md, usa), and jynneost m (bavarian nordic, hellerup, denmark). jynneost m is an attenuated, non-replicating orthopoxvirus vaccine derived from modified vaccinia ankara-bavarian nordic (mva-bn strain). it was licensed by the us fda in september 2019 and is now indicated for prevention of smallpox and monkeypox disease (36, 37). acam2000® is a live, replication-competent vaccinia virus. these two vaccines differ significantly. there is a risk of serious adverse events associated with acam2000® (e.g. eczema vaccinatum, myopericarditis, and post-vaccine encephalitis) because it is replication-competent. in contrast, there are fewer contraindications with jynneost m , this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index z. tehranchinia et al. 6 and there is no risk of inadvertent inoculations and autoinoculations (31, 37). in jynneost m , two vaccine doses are administered 28 days apart, with vaccine protection conferred after two weeks. on the other hand, vaccination with acam2000® involves one dose and provides peak protection within 28 days (30). 8. conclusions as global cases of monkeypox continue to rise in many countries, it is possible that the virus has evolved to become more transmissible during this outbreak. although the covid-19 pandemic is not yet expected to be exacerbated by the outbreak of monkeypox, it is imperative for the public healthcare authorities to establish a nationwide surveillance system as well as taking appropriate pre-cautionary measures before the ongoing monkeypox outbreak creates a critical situation. in order to control the disease, regional capacity should be strengthened for early detection, prevention, and management in developing countries, because vaccines and drugs are not readily available. currently, all efforts should be concentrated on preventing the entry of monkeypox into healthcare facilities that are still dealing with the effects of the ongoing covid-19 pandemic. finally, physicians need to keep a high index of clinical suspicion for the monkeypox disease and follow the standard protocols for diagnosis, reporting, and isolation. 9. declarations 9.1. acknowledgments not applicable. 9.2. conflict of interest the authors declare that they have no conflict of interest. 9.3. funding information none. 9.4. authors contribution reza mahmoud robati and hamideh moravvej contributed to the study’s conception and design. data collection was performed by zohreh tehranchinia and hamideh moravvej. the first draft of the manuscript was written by mojtaba memariani, zohreh tehranchinia, and hamed memariani and revised by reza mahmoud robati. all authors read and approved the final manuscript. references 1. memariani h, memariani m. therapeutic and prophylactic potential of anti-microbial peptides against coronaviruses. ir j med sci. 2020;189(4):1153-4. 2. world health organization. who director-general declares the ongoing monkeypox outbreak a public health emergency of international concern. 2022. 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2022;12(17):2190. 9. sklenovská n. monkeypox virus. in: malik ys, singh, r.k., dhama, k., editor. animal-origin viral zoonoses livestock diseases and management. singapore: springer; 2020. p. 39-68. 10. kannan s, shaik syed ali p, sheeza a. monkeypox: epidemiology, mode of transmission, clinical features, genetic clades and molecular properties. eur rev med pharmacol sci. 2022;26(16):5983-90. 11. isidro j, borges v, pinto m, sobral d, santos jd, nunes a, et al. phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus. nat med. 2022;28(8):1569-72. 12. quarleri j, delpino mv, galvan v. monkeypox: considerations for the understanding and containment of the current outbreak in non-endemic countries. geroscience. 2022;44(4):2095-103. 13. reynolds mg, doty jb, mccollum am, olson va, nakazawa y. monkeypox re-emergence in africa: a call to expand the concept and practice of one health. expert rev anti infect ther. 2019;17(2):129-39. 14. bunge em, hoet b, chen l, lienert f, weidenthaler h, baer lr, et al. the changing epidemiology of human monkeypox-a potential threat? a systematic review. plos negl trop dis. 2022;16(2):e0010141. 15. salcedo rm, madariaga mg. monkeypox (hmpxv infecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e19 tion): a practical review. am j med. 2022; [forthcoming]. 16. kaler j, hussain a, flores g, kheiri s, desrosiers d. monkeypox: a comprehensive review of transmission, pathogenesis, and manifestation. cureus. 2022;14(7):e26531. 17. ligon bl. monkeypox: a review of the history and emergence in the western hemisphere. semin pediatr infect dis. 2004;15(4):280-7. 18. nguyen py, ajisegiri ws, costantino v, chughtai aa, macintyre cr. reemergence of human monkeypox and declining population immunity in the context of urbanization, nigeria, 2017-2020. emerg infect dis. 2021;27(4):1007-14. 19. zumla a, valdoleiros sr, haider n, asogun d, ntoumi f, petersen e, et al. monkeypox outbreaks outside endemic regions: scientific and social priorities. lancet infect dis. 2022;22(7):929-31. 20. who recommends new name for monkeypox disease 2022 [available from: https://www.who.int/news/item/28-11-2022-whorecommends-new-name-for-monkeypox-disease]. 21. otu a, ebenso b, walley j, barcelo jm, ochu cl. global human monkeypox outbreak: atypical presentation demanding urgent public health action. lancet microbe. 2022;3(8):e554-e5. 22. cheema ay, ogedegbe oj, munir m, alugba g, ojo tk. monkeypox: a review of clinical features, diagnosis, and treatment. cureus. 2022;14(7):e26756. 23. singhal t, kabra sk, lodha r. monkeypox: a review. indian j pediatr. 2022;89(10):955-60. 24. patel a, bilinska j, tam jch, da silva fontoura d, mason cy, daunt a, et al. clinical features and novel presentations of human monkeypox in a central london centre during the 2022 outbreak: descriptive case series. bmj. 2022;378:e072410. 25. koenig kl, bey ck, marty am. monkeypox 2022: a primer and identify-isolate-inform (3i) tool for emergency medical services professionals. prehosp disaster med. 2022;37(5):687-92. 26. van nispen c, reffett t, long b, gottlieb m, frawley tc. diagnosis and management of monkeypox: a review for the emergency clinician. ann emerg med. 2023;81(1):2030. 27. huang ya, howard-jones ar, durrani s, wang z, williams pc. monkeypox: a clinical update for paediatricians. j paediatr child health. 2022;58(9):1532-8. 28. adler h, gould s, hine p, snell lb, wong w, houlihan cf, et al. clinical features and management of human monkeypox: a retrospective observational study in the uk. lancet infect dis. 2022;22(8):1153-62. 29. see kc. vaccination for monkeypox virus infection in humans: a review of key considerations. vaccines (basel). 2022;10(8):1342. 30. tiecco g, degli antoni m, storti s, tomasoni lr, castelli f, quiros-roldan e. monkeypox, a literature review: what is new and where does this concerning virus come from? viruses. 2022;14(9):1894. 31. di gennaro f, veronese n, marotta c, shin ji, koyanagi a, silenzi a, et al. human monkeypox: a comprehensive narrative review and analysis of the public health implications. microorganisms. 2022;10(8):1633. 32. pastula dm, tyler kl. an overview of monkeypox virus and its neuroinvasive potential. ann neurol. 2022;92(4):527-31. 33. sherwat a, brooks jt, birnkrant d, kim p. tecovirimat and the treatment of monkeypox past, present, and future considerations. n engl j med. 2022;387(7):579-81. 34. ajmera km, goyal l, pandit t, pandit r. monkeypox an emerging pandemic. idcases. 2022;29:e01587. 35. petersen e, zumla a, hui ds, blumberg l, valdoleiros sr, amao l, et al. vaccination for monkeypox prevention in persons with high-risk sexual behaviours to control ongoing outbreak of monkeypox virus clade 3. int j infect dis. 2022;122:569-71. 36. memariani m, memariani h. multinational monkeypox outbreak: what do we know and what should we do? ir j med sci. 2022:1-2. 37. rizk jg, lippi g, henry bm, forthal dn, rizk y. prevention and treatment of monkeypox. drugs. 2022;82(9):957-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction virology a brief history of monkeypox the ongoing global outbreak clinical features and differential diagnosis clinical management prevention conclusions declarations references archives of academic emergency medicine. 2023; 11(1): e26 rev i ew art i c l e clinical characteristics, course, and outcomes of vertebral artery dissections in the postpartum period; a pooled analysis of published case reports rehab adel diab1,6∗, nour shaheen2, abdelrahman mohamed2, mahmoud tarek hefnawy3,6, dilawer chofan charo4,6, mostafa meshref5,6 1. faculty of medicine, al-azhar university, cairo, egypt. 2. faculty of medicine, alexandria university, alexandria, egypt. 3. faculty of medicine, zagazig university, medical research group of egypt, cairo, egypt. 4. general surgery department, national hospital in latakia, latakia, syria. 5. neurology department, faculty of medicine, al-azhar university, cairo, egypt. 6. medical research group of egypt (mrge), research department, cairo, egypt. received: december 2022; accepted: january 2023; published online: 4 march 2023 abstract: introduction: vertebral artery dissection (vad) is a rare, but life-threatening condition. compared to the general population, pregnant and postpartum women are more likely to develop vad. spontaneous arterial dissections have an ambiguous pathophysiology and may be difficult to manage. this study aimed to pool and analyze the data of published cases in this regard. methods: we conducted a literature search on february 24, 2022, using mesh terms of interest in pubmed, google scholar, ovid, web of science, and scopus databases to find studies on vad following childbirth. results: a total of 28 studies were included in this review based on a database search. in the studies, 44 postpartum vad (ppvad) patients with a mean age of 34.26 ± 3.5 years were included. it took an average of 24.37± 13.7 days from delivery to dissection. 64% of the patients had developed unilateral dissection and 36% had developed bilateral dissection; 70% reported full recovery, and 9% did not achieve full recovery. the most common symptoms were headaches (89%), neck pain (64%), and hypertension (52%). the most common methods of diagnosis were magnetic resonance imaging (mri) (64%) and computed tomography (ct) angiography (cta) scan (66%). only 8 (18%) cases reported the use of electrocardiography (ecg). the recorded outcomes of the patients with unilateral and bilateral postpartum vad showed no statistical difference. most of the included studies recommend early suspension and management for a better prognosis and prevention of complications. conclusion: ppvad is a severe medical condition but most cases were fully recovered after an early and proper antithrombotic plan for each case scenario. keywords: vertebral artery; vertebrobasilar insufficiency; postpartum period; vertebral artery dissection cite this article as: adel diab r, shaheen n, mohamed a, tarek hefnawy m, chofan charo d, meshref m. clinical characteristics, course, and outcomes of vertebral artery dissections in the postpartum period; a pooled analysis of published case reports. arch acad emerg med. 2023; 11(1): e26. https://doi.org/10.22037/aaem.v11i1.1814. 1. introduction vertebral artery dissection (vad) can be extracranial or intracranial and unilateral or bilateral with different prognoses ranging from complete healing to serious neurological sequels (1). dissection of cervical, vertebral, or carotid arter∗corresponding author: rehab adel diab; faculty of medicine, al-azhar university, cairo, egypt. postal code: 44718 email: rehab_diab97research@outlook.com. tel: +20 127 245 1274, orcid: https://orcid.org/0000-0002-6552-4900. ies is rare, but once occurring, it can be fatal. vads commonly occur in young poststroke patients but rarely affect patients in the postpartum period (2, 3). the postpartum period is a distressing period associated with headaches and other symptoms that make the diagnosis of postpartum vertebral artery dissection (ppvad) challenging due to common symptoms between both. the incidence of headache reporting in the postpartum period is ranging from 11% to 80% (4), so the vertebral artery dissection should be considered in differential diagnosis for patients suffering from headaches in the postpartum period for early diagnosis and better outthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. adel diab et al. 2 come. the incidence of spontaneous vertebral artery dissection ranges from 1 to 1.5 per 100.00, annually (5). 2.4% of symptomatic spontaneous vad cases presented in the postpartum period and women are 2.5 times more likely than men to get vad (3, 6). vad can lead to stroke with an estimated incidence of one per 100,000 individuals annually (7), and stroke can lead to vad (7, 8). the etiology of spontaneous postpartum vertebral artery dissection is still unknown, but there are potential risk factors that can be considered to predispose it in the postpartum period, like hormonal and hemodynamic changes occurring during pregnancy and valsalva maneuver (9). due to the lack of literature about the clinical picture and management of ppvad, our study aimed to pool and analyze the most frequent symptoms, signs, complications, and the strategies that are widely used in management of these cases. 2. methods 2.1. search strategy the literature review was conducted on feb 24, 2022, using the terms (("vertebral artery"[mesh]) or ("vertebral artery dissection"[mesh] or "vertebrobasilar insufficiency"[mesh] or "pica syndrome" [supplementary concept]) and ("postpartum*"[mesh]). using pubmed, google scholar, ovid, web of science, and scopus databases, we searched for case series and case reports on vad following childbirth. researchers independently conducted the search to find the studies matching the keywords. all studies reporting cases of vertebral artery dissection after childbirth were included in the search (figure 1). the analysis did not include review articles or consensus statements. preferred reporting items for systematic reviews and meta-analyses (prisma) was used to present inclusions and exclusions (10). 2.2. study selection, data extraction, and data analysis articles were selected based on predetermined criteria after title and abstract screening by two independent reviewers. the inclusion criteria were clinical case reports or series that reported the clinical characteristics, treatment protocol, and outcomes of ppvad. based on the following exclusion criteria, several steps were taken to select included studies. 1) studies that are not tailored for humans (such as in vitro or animal studies), 2) research not collecting original primary data (review, protocol, editorial, letter, etc.), 3) no full text of the research results was provided (i.e., abstracts of conference posters), and 4) studies in a language other than english. 2.3. quality assessment the overall quality of the case series and the case reports was assessed. the joanna briggs institute ( jbi) critical appraisal checklist was used in the quality assessment of case reports (11), while the nih quality assessment tool was used for case series (12) (appendix 1 & 2). 2.4. data analysis python 3.0 was used for data management and cleaning as well as statistical analysis. a comparison was made between patients that suffered from unilateral dissection and patients that faced a bilateral dissection. other variables were investigated as well, like whether having multiple previous pregnancies affected the final outcome or time to dissection. the mann-whitney test was used for numerical data, and fischer’s exact test was used for categorical data. 3. results 3.1. characteristics of included studies in total, 163 studies were found in pubmed, google scholar, ovid, web of science, and scopus using our search criteria. a total of 74 full-text articles were reviewed after excluding duplicate studies, studies lacking clinical data, review articles, and articles unrelated to our study objective. based on the review, 32 studies met our inclusion criteria; therefore, 32 studies about vertebral artery dissection after birth were reviewed and analyzed (figure 1). characteristics of included studies are summarized in tables 1 and 2. studies most commonly reported diagnosis via mri with 28 (64%) and ct-angiography with 29 (66%) case. only 8 (18%) cases reported the use of ecg as a diagnostic tool for vad alongside one or more of the main modalities mentioned. based on the reported data, most studies used anticoagulant and antiplatelet drugs to treat vad, including warfarin, aspirin, and enoxaparin as well as antihypertensive drugs. 3.2. pooled analysis of reported cases pooled analysis of cases is presented in table 3. the studies included a total of 44 patients who suffered from postpartum vertebral dissection with a mean age of 34.26 ± 3.50 years. the average time between delivery and dissection was 24.37 ± 13.7 days. 28 (64%) of the patients developed unilateral dissection, whereas the remaining 16 (36%) developed bilateral dissection. 20 (45%) of the patients reported delivering via vaginal delivery, 16 (36%) reported delivering via csections, whereas the remaining 8 (19%) did not report a specific delivery type. the most frequent signs and symptoms were headache 39 (89%) and neck pain 28 (64%). 23 (52%) of the patients had high blood pressure after pregnancy, whereas only 4 (9%) pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e26 table 1: summary of the included studies; number of patients, mean age (years), obstetric code, delivery type, and vessels affected study id no. mean age (years) obstetric code delivery type affected vessels (side) azad, 2021(19) 12 31.8 na 9 vaginal 3 cesarean 2 vertebral (r), 4 vertebral (l),6 vertebral (both) borelli, 2012(31) 1 32 g2p2 cesarean vertebral (l) brantley, 2012(14) 1 32 g3p3 vaginal vertebral (l), lad, im(l) cenkowski, 2012(36) 1 35 g2p2 na vertebral (r), obtuse marginal coronary artery drazin, 2012(24) 1 37 pg vaginal vertebral (both) drăghici, 2021(6) 1 37 g3p3 cesarean vertebral (r), basilar feldman, 2019(19) 1 41 g5p4 cesarean vertebral (r), rsca finley, 2015(9) 1 35 g5p5 cesarean vertebral (r) gasecki,1999(42) 4 32.5 g6p4 3 vaginal 1 cesarean one vertebral, three internal carotids gomez-rojas, 2020(44) 1 37 na na vertebral (both) jeannie, 2014(41) 5 33.4 na 4 vaginal 1 cesarean 1 vertebral (r ), 3 vertebral (both), 2 internal carotid (l) kaplan, 1993(38) 1 41 g4p4 vaginal vertebral (l) keane, 2019(26) 1 30 g2p2 cesarean vertebral (l), internal carotid (l), pica kelft, 1992(27) 1 31 pg vaginal delivery vertebral (r) basilar artery levy, 2011(32) 1 32 g2p3 vaginal vertebral, transverse, and sigmoid sinuses (l) manasewitsch, 2020(25) 1 31 na cesarean vertebral (l) mckinney, 2010(34) 1 41 na cesarean vertebral (both), basilar, pca mikeal levey 2011(32) 1 32 p3g3 vaginal vertebral (r), transverse and sigmoid sinus (l) mitchell, la. 2014(39) 1 na na na vertebral (both) monari,2021(45) 1 39 na cesarean vertebral (r) nehme, 2020(23) 1 36 g2p2 cesarean vertebral (both) nishimura, 2015(29) 1 35 g1p1 na vertebral (r) pires, 2011(33) 1 31 g1p1 cesarean vertebral (both) previtra, 2012(37) 1 34 na na vertebral (r) sano, k. 2021(40) 1 38 g2p2 vaginal vertebral (l), mca (both), pca (both) shanmugalingam, 2016(43) 4 31.25 g2p2 cesarean 1 vertebral (r), 3 vertebral intramural thrombus simon, 2015(30) 1 31 g4p4 vaginal vertebral (l), internal carotid (both) spence, 2016(35) 1 33 g2p2 na vertebral (both), lad, lcx, celiac, sma, ima not applicable (na), right (r), left (l), gravida 2 /para 2 (g2p2), pg: primigravida, lad: left anterior descending artery; ima: internal mary artery; rsca: right subclavian artery; pica: posterior inferior cerebellar artery; pca: posterior cerebral artery; mca: posterior cerebral artery; lcx: left circumflex artery ; sma: superior mesenteric artery. tients reported hypertension during pregnancy as well. additionally, 14 (32%) of the patients had associated syndromes including opal ski syndrome, help syndrome, horner syndrome, and postpartum angiopathy. based on the reported data, 2 (5%) patients had at least one failed pregnancy, 5 (11%) patients had trauma injury, 7 (16%) patients had surgical history (3 caesareans, 1 vacuumassisted vaginal delivery, 1 thyroidectomy, and 2 diagnostic laparoscopies. as for the final outcome, 31 (70%) reported being fully recovered, 4 (9%) did not undergo full recovery and the remaining 9 (21%) did not provide data for follow-up final outcomes. there was no statistical difference between unilateral and bilateral cases and also gravid 1 or >1 regarding age distribution, time from delivery to dissection, and final outcomes (table 4). 4. discussion vad is a rare and serious condition in the postpartum period. according to literature, cervical dissection represents 6% of spontaneous dissections in females under 50 years of age (8). using our results, we found that the mean age of the patients was 34.26 ± 3.50 years. cervical dissections in the postpartum period mainly include vertebral and carotid artery dissections; both are reported to occur unilaterally or bilaterally (9, 13). our study showed that 64% of the included patients developed unilateral vertebral artery dissection while this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. adel diab et al. 4 table 2: summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome study id time from delivery (days) clinical presentation comorbidities investigation treatment outcome azad, 2021(19) 12 headache was reported in all cases and some reported neck pain, weakness, and stroke, and a single case reported sah htn of pregnancy in all cases, some reported hellp syndrome, loeys-dietz syndrome, factor v ledin syndrome, reversible vasoconstriction syndrome and mthfr mutation mri showed the affected arteries in each patient anticoagulants and endovascular surgery full recovery borelli, 2012(31) 10 headache, hypertension, dizziness, and mild right-side weakness hellp syndrome and preeclampsia mri showed bilateral left predominant thalamic infarction, and ct angiogram showed left vertebral artery dissection at v3 and v4 segments antiplatelet (aspirin) na brantley, 2012(14) 7 hypertension and neck pain acs ecg with cardiac biomarkers: suggestive for nstemi mri: not done ct-angiogram: dissection of the left vertebral artery at the level of c6 to c7 and dissection involving the lad, not the main coronary echo 6 days later: no motion, valvular abnormalities with the normal system, ic function anticoagulant therapy (heparin), antiplatelets (aspirin, clopidogrel) and cabg for coronary dissection full recovery cenkowski 2012(36) 210 nausea, vomiting, chest pain with elevated cardiac enzymes, and one month later presented with numbness in her left arm and face. na ecg: inferior stemi ct angiogram: dissection of r.t vertebral v1 segment with aneurysmal dilatation and obtuse marginal coronary artery. echo: ef= 50-55%. antiplatelet (warfarin) and antiplatelet (aspirin, clopidogrel), statins, metoprolol, ramipril, nitroglycerin na drazin, 2012(24) immediately headache, neck pain, hypertension, photophobia and sah na mri: beaded appearance along cervical segments of both vertebral arteries. ct-angiogram: narrowed vertebral arteries. anticoagulants therapy full recovery drăghici, 2021(6) 56 headache, neck pain dizziness, palsies, stroke, dysphagia, and extracranial stroke autoimmune thyroiditis mri: bilateral infarction of the pons. ct-angiogram: filling defect of the basilar artery with narrowing of the right vertebral artery suggesting dissection anticoagulant therapy (heparin with enoxaparin) and antiplatelets (aspirin) na feldman, 2019(28) 3 visual symptoms, sensory deficit, intracranial stroke na mri: restricted diffusion in r.t cerebellum, right pons, and midbrain ct-angiogram: areas of narrowing and dilatation artery vertebral artery aspirin full recovery finley, 2015(9) 21 headache, hypertension, dizziness, vertigo, nausea, vomiting, and visual symptoms na mri: diffusion defect within the cerebellar hemispheres bilateral more in the r.t ct-angiogram: r.t vad with variations in the l.t vertebral artery at the junction with the proximal aorta. anticoagulant therapy (oral warfarin) full recovery this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e26 table 2: summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome study id time from delivery (days) clinical presentation comorbidities investigation treatment outcome gasecki, 1999(42) 14 headache, vertigo, visual symptoms, cranial nerves palsies, horner, right side ataxia, sensory deficit, and speech abnormalities na mri: some cases show no brain abnormalities, and the others show diffusion defect at areas supplied by the occluded artery ct-angiogram: suggestive of dissection of either vertebral or carotid artery anticoagulant therapy (heparin) 3 full recoveries and one death gomezrojas. 2020(44) na headache, dizziness, vertigo, hypertension, nausea, vomiting, sensory deficit, and neck pain na mri: showed a large area of ischemia at pica territory and smaller areas at the left superior parasagittal cerebellum ct-angiogram: narrowing of the caliber diameter suggesting dissection of both vertebral arteries anticoagulants (warfarin and solitary case used heparin) full recovery jeannie, 2014(41) 23 headache, hypertension, neck pain, visual symptoms, intracranial sah na mri, mra and ct-angiogram: suggesting dissection of vertebral and carotid arteries for each corresponding case anticoagulant therapy (oral or heparin) and dual antiplatelets full recovery kaplan, 1993(38) 17 headache, hypertension, nausea, neck pain, visual symptoms, extracranial stroke na mri: infarction in the left medulla and cerebellar hemisphere. ct-angiogram: dissection of the left vertebral and left pica antiplatelet (aspirin), statins and amlodipine not fully recovered keane, 2019(26) 3 hypertension, headache, neck pain and subarachnoid hemorrhage na mri: na ct-angiogram left vertebral artery dissection with pseudoaneurysm balloon occlusion of the vertebral artery with anticoagulant (warfarin) na kelft, 1992(27) 1 headache, confusion, ataxia, horner sign, confusion, ipsilateral ataxia, nystagmus, hpa glesia on right side of face and left side of the body. na mri: r.t thalamic, post limb of internal capsule and occipital lobe ischemia. ct-angiogram: normal vertebral artery -angiogram: dissection of the basilar artery with right vertebral affection with proximal thrombosis antiplatelets (ticlopidine) fully recovered levy, 2011(32) na headache, hypertension, dizziness, nausea, vomiting, sensory deficit, cranial nerve palsies and intracranial stroke opalski syndrome mri: infarction in the brainstem and cerebellum. ct-venogram: cvst in the transverse and sigmoid sinus echo: mild tr anticoagulant therapy (heparin) full recovery manasewitsch, 2020(3) 10 headache, vertigo, nausea, vomiting, gait abnormalities, ataxia, and stroke chorioamnionitis, ida mri: infarction at the left cerebellar hemisphere ct-angiogram: dissection of the left vertebral artery and left pica anticoagulant therapy (enoxaparin) na this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. adel diab et al. 6 table 2: summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome study id time from delivery (days) clinical presentation comorbidities investigation treatment outcome mckinney, 2010(34) 6 hypertension and headache, visual symptoms, and stroke na mri: multiple infarctions at areas supplied by post circulation. ct-angiogram: dissection of both vertebral and basilar arteries with proximal segments dilatation of the posterior circulation. anticoagulants (heparin), antiplatelet (aspirin), nicardipine infusion and levetiracetam not fully recovered mikeal levey, 2011(32) 14 headache, neck pain, hypertension, vomiting, dizziness, vertigo, visual symptoms, sensory deficit, and intracranial and extracranial stroke opalski syndrome mri: infarction of medulla, cerebellum, and pyramidal dissection ct-angiogram not done echo: mild tr anticoagulants (heparin) full recovery mitchell, 2014(39) 10 headache, dizziness, visual symptoms, sensory deficit, and stroke na mri: intramedullary infarction. ct-angiogram: the abnormal appearance of the right vertebral artery antiplatelet (aspirin and clopidogrel) not fully recovered monari, 2021(5) na headache, nausea, vomiting, dizziness, vertigo, visual symptoms, gait abnormalities and stroke na mri: infarction of the posterolateral portion of the brain bulb. ct-angiogram: right vertebral artery dissection. anticoagulant therapy (heparin and enoxaparin) and antiplatelet (aspirin and clopidogrel) na nehme, 2020(23) 10 headache, neck pain, hypertension, visual symptoms, gait abnormalities, sah na mri: hematomas at dissection sites ct-angiogram: dissection of both vertebral arteries endovascular surgery with ccb and antiplatelets (aspirin) na nishimura, 2015(29) 5 headache, neck pain, hypertension, and seizures pres mri: infarction in the subcortical white matter ct-angiogram: stenosis of the right vertebral artery magnesium sulfate and nicardipine full recovery pires, 2011(33) 18 headache, neck pain, migraine, anosognosia, dysarthria, na mri: contraindicated. digital subtraction angiogram: dissection of both ica and left vertebral artery (string beads) anticoagulant therapy not fully recovered previtra, 2012(37) 14-21 headache, neck pain, vertigo, nausea, vomiting, right faciobrachial syndrome, intracranial stroke history of cervical manipulation brain mri was normal, sat mri did not show dissection in vertebral (r) anticoagulants, rehabilitation full recovery sano, 2021(40) 18 headache, neck pain and subarachnoid hemorrhage na mri: infarction in both basal ganglia and right occipital cortex ct-angiogram: na lowering bp without any thrombolytic therapy full recovery shanmugalingam, 2016(43) 5.3 headache, hypertension, dizziness, and neck pain na mri: no evidence of post circulation infarction. ct-angiogram: features suggesting dissection or intramural thrombus of vertebral arteries anticoagulant therapy or antiplatelets full recovery this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e26 table 2: summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome study id time from delivery (days) clinical presentation comorbidities investigation treatment outcome simon, 2015(30) 21 headache with mildly decreased facial sensation endometriosis and anemia mri: increased intensity of the vertebral and carotid arteries bilaterally with near occlusion of the r.t internal carotid ct-angiogram: dissection of the left vertebral and bilateral internal carotid anticoagulant therapy (heparin and transferred to another hospital) na spence, 2016(35) 21 hypertension and headache and neck pain repaired sinus venous asd, acs ecg: anterior and inferior ste with reciprocal std in the lateral leads mri: na ct-angiogram: dissection of both vertebral arteries, lad, lcx, celiac, sma, and ma echo: no abnormalities detected. revascularization and antiplatelet (aspirin, clopidogrel), statins, bb, amlodipine, ramipril, nitroglycerin full recovery sah: subarachnoid hemorrhage; htn: hypertension; hellp: hemolysis, elevated liver enzymes and low platelets; mthfr: methylenetetrahydrofolate reductase; mri: magnetic resonance imaging; ct: computed tomography; ecg: electrocardiography; nstemi: non-st-segment elevation myocardial infarction; lad: left anterior descending artery; echo: echocardiography. 36% developed bilateral vertebral artery dissection. some studies reported the extension of vad to include the basilar artery and other studies presented multiple vessel dissections as reported in a previous study (14) in which there was a rare case of postpartum multi-arterial dissection, involving the vertebral artery, coronary artery, and the internal mammary artery (6, 15). the exact incidence rate of cervical dissection is unknown; however, it has an estimated incidence of 2.6–3.0 cases per 100,000 population per year, with vad being 3–5 times less frequent than carotid artery dissection (16, 17). females are 2.5 times more likely to get vad than males (17). moreover, it has been reported that 2.4% of cervical dissections occur in females in the postpartum period (18). in addition, vad is a leading cause of ischemic stroke among young people (19). postpartum cervical dissection can be caused by a variety of underlying factors, but the mechanisms are unclear. there are several hypotheses in literature regarding the effects of pregnancy hormones, especially progesterone, on collagen synthesis in the tunica media of vessels, increasing its sensitivity to systemic stressors like hypertension (6, 7, 9, 19). approximately 31 (70%) of patients presented with neurological symptoms. the main clinical presentation of vad is typically acute, severe neck pain in the occipito-cervical region, either with or without headache (20). our results showed that vad in females in the postpartum period was mainly presented with headache as the commonest presentation in 39 (89%) of the cases followed by neck pain in 28 (64%), hypertension in 23 (52%) and visual defects symptoms in 17 (39%) of the cases. physical examination in vad may reveal nystagmus, truncal ataxia, loss of taste, impairment in pain and thermal sensation, and ophthalmoplegia; however, that clinical picture may be vague, and symptoms overlap with that of the postpartum period making the differential diagnosis even more difficult (20). investigations used to diagnose vad are ct, cta, and mri. ct scan can show the ischemia in the posterior fossa, subarachnoid hemorrhage, vertebral artery occlusion and mural thrombus. mri can also prove the diagnosis but is not always available. cta can easily show any regularity or thickening in the vascular wall, this makes the cta the investigation of choice in the case of vad (20). our finding showed that two or more of these investigations are usually used to establish the diagnosis or complications and ct was the commonest investigation used with 66% and mri with 64% of cases. regarding the management of vad, antithrombotic therapy should be started as soon as possible. both antiplatelets and anticoagulants are the main lines in treatment, in a previous randomized trial (cadiss trial) there was no difference in the efficacy of anticoagulants and antiplatelets in preventing stroke in patients suffering from vertical artery dissections including carotid and vertebral arteries (21). additionally, this conclusion was supported by a case series study of twelve patients who suffered cervical dissections, in which there was no difference in prognosis or complications (19). anticoagulation is to be started with low-molecular-weight or unfractionated heparin followed by oral anticoagulation, while antiplatelets are applied for mono or dual therapy (10). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. adel diab et al. 8 figure 1: prisma flow diagram of study screening and inclusion. antiplatelets are widely preferred because of their availability and low cost. according to existing guidelines, antithrombotics should be continued for about three to six months, with no clear clinical evidence of the exact duration yet (1, 9). in the absence of exact duration and choice of antithrombotic strategy, it is recommended to be individually adapted according to each case scenario (22). clearly, this was evident from the management strategies in our included reports, in which antithrombotic choice was respected. 31 patients (70%) showed a full recovery after proper management while 4 cases (9%) showed incomplete recovery and the rest were not reported. although postpartum vad can carry a good prognosis it can cause permanent damages if complicated with stroke and infarction. vad can develop complications such as cerebellar and brain stem infarctions, subarachnoid hemorrhage, pseudoaneurysm and cranial nerves affection (20). and all of these complications are reported in postpartum vad in the included cases, either as a sign or a complication, along with stroke that developed in 10 patients (23%) and the subarachnoid hemorrhage that developed in 6 patients (14%); thus, early diagnosis and management of vad are required, the sooner the better. 5. limitations and recommendations this study should be considered in light of several limitations. the first limitation is that there is a small number this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e26 table 3: pooled analysis of data of patients with post-partum vertebral artery dissection (n = 44) variables number (%) age (year) mean ± sd 34.26 ± 3.50 previous deliveries no 30 (68.1) signs and symptoms headache 39 (88.3) neck pain 28 (63.6) hypertension 23 (52.2) visual symptoms 17 (38.6) stroke 10 (22.7) dizziness 10(22.7) nausea 10 (22.7) vomiting 9 (20.4) vertigo 8 (18.2) sensory deficits 7 (15.9) subarachnoid hemorrhage 6 (13.6) dysphagia 5 (11.3) ataxia 4 (9.0) cranial nerve 3 (6.8) gait problems 3 (6.8) palsies 3 (6.8) hearing changes 2 (4.5) weakness 1 (2.2) delivery type vaginal 20 (45.4) cesarean 16 (36.4) arteries dissected unilateral dissection 28 (63.6) bilateral dissection 16 (36.4) pseudo-aneurysm 4 (9.0) recovery status full recovery 31 (70.4) not fully recovered 4 (9.0) data are presented as frequency (%). sd: standard deviation. of cases, there is also lack of follow-up data. the specific dose of antithrombotic is different in each case scenario and cannot be generalized. secondly, some clinical pictures are not completely reported when the cases are transported from one center to another or in case of long duration of hospital admission, in which not all the complications or side effects are fairly mentioned. the lack of literature about postpartum dissections is a remarkable limitation so further reports and high-quality evidence-based studies are strongly recommended. 6. conclusions ppvad is a severe medical condition; most cases were fully recovered after an early and proper antithrombotic plan for each case scenario. headache and neck pain were the commonest ppvad presentations. age, type of delivery, and gravida were not statistically associated with ppvad. unilateral and bilateral postpartum vad showed no statistical difference in the recorded outcomes of the patients. most of the included studies recommend early suspicion and management for a better prognosis and prevention of complications. 7. declarations 7.1. acknowledgments we would to express our sincere thanks to all authors of the included studies and to medical research group of egypt under supervision of dr. ahmed negida for their support and encouragement in carrying out this project. 7.2. conflict of interest the authors have no conflict of interest to declare. 7.3. fundings and supports none. 7.4. authors’ contribution rehab adel diab: conceptualization, writing-original draft, review, and editing. nour shaheen: methodology, writingoriginal draft, review, and editing. abdelrahman mohamed: formal analysis mahmoud tarek hefnawy: writing-original draft, review, and editing dilawer chofan charo: writingoriginal draft, review, and editing mostafa meshref: writingoriginal draft, review, and editing. all authors read and approved final version of the manuscript. 7.5. ethics approval not applicable. 7.6. data availability statement the data was extracted from online published articles. references 1. debette s, leys d. cervical-artery dissections: predisposing factors, diagnosis, and outcome. the lancet neurology. 2009;8(7):668-78. 2. sances g, granella f, nappi r, 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associated with pregnancy and puerperium: a study in public hospitals of ile de france. stroke. 1995;26(6):930-6. 9. finley a, rogers b, richards t, vogel h. postpartum vertebral artery dissection. case reports. 2015;2015:bcr2015211872. 10. peng j, liu z, luo c, chen l, hou x, xiao l, et al. treatment of cervical artery dissection: antithrombotics, thrombolysis, and endovascular therapy. biomed research international. 2017;2017. 11. moola s, munn z, tufanaru c, aromatari se sk, sfetcu r. chapter 7: systematic reviews of etiology and risk. jbi manual for evidence synthesis. 2020. 2020. 12. nhlbi n. study quality assessment tools national heart lung and blood institute | nhlbi, nih: u.s. department of health and human services; 2021 [available from: http://nhlbi.nih.gov/. 13. shin jh, suh dc, choi cg, lee hk. vertebral artery dissection: spectrum of imaging findings with emphasis on angiography and correlation with clinical presentation. radiographics. 2000;20(6):1687-96. 14. brantley hp, cabarrus br, movahed a. spontaneous multiarterial dissection immediately after childbirth. texas heart institute journal. 2012;39(5):683. 15. iltumur k, karahan z, ozmen s, danis r, toprak n. spontaneous coronary artery dissection during hemodialysis in the post-abortion period. international journal of cardiology. 2008;127(2):e45-e7. 16. kim y-k, schulman s. cervical artery dissection: pathology, epidemiology and management. thrombosis research. 2009;123(6):810-21. 17. chang aj, mylonakis e, karanasias p, douglas f, gold r, editors. spontaneous bilateral vertebral artery dissections: case report and literature review. mayo clinic proceedings; 1999: elsevier. 18. arnold m, camus-jacqmin m, stapf c, ducros a, viswanathan a, berthet k, et al. postpartum cervicocephalic artery dissection. stroke. 2008;39(8):2377-9. 19. azad ha, prasad n, shlobin na, mitra a, cloney mb, hopkins bs, et al. clinical characteristics, course, and outcomes of vertebral artery dissections in the postpartum period. neurosurgery. 2021;89(5):792-9. 20. rathbun s. the surgeon general’s call to action to prevent deep vein thrombosis and pulmonary embolism. circulation. 2009;119(15):e480-e2. 21. investigators ct. antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (cadiss): a randomised trial. the lancet neurology. 2015;14(4):361-7. 22. kennedy f, lanfranconi s, hicks c, reid j, gompertz p, price c, et al. antiplatelets vs anticoagulation for dissection: cadiss nonrandomized arm and meta-analysis. neurology. 2012;79(7):686-9. 23. nehme a, létourneau-guillon l, odier c, poppe ay. clinical reasoning: a 36-year-old woman presenting with headache postpartum. neurology. 2021;96(11):e1585-e9. 24. drazin d, rosner j, shirzadi a, phuphanich s. postpartum extracranial bilateral vertebral artery dissection mimicking subarachnoid hemorrhage. the neurologist. 2012;18(3):149-51. 25. manasewitsch nt, hanfy aa, beutler bd, antwiamoabeng d, taha m, elnaggar m, et al. postpartum vertebral artery dissection: case report and review of the literature. thrombosis journal. 2020;18(1). 26. keane jl, liew lp. postpartum cervical manipulation, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e26 vertebral artery dissection and reversible cerebral vasoconstriction: a case report. journal of clinical gynecology and obstetrics. 2019;8(3):97-102. 27. van de kelft e, kunnen j, truyen l, heytens l. postpartum dissecting aneurysm of the basilar artery. stroke. 1992;23(1):114-6. 28. feldman jb, kumaraswami s. cesarean hysterectomy in a parturient with morbidly adherent placenta complicated by postoperative ischemic stroke secondary to vertebral artery dissection: a case report. a&a practice. 2019;12(1):9-14. 29. nishimura m, hiraoka e, kanazawa k, akita h. postpartum vertebral artery dissection with posterior reversible encephalopathy syndrome. bmj case reports. 2015:bcr2014207332. 30. simon el, griffin g, bosman e. bilateral carotid and vertebral artery dissection: a life-threatening cause of postpartum headache. am j emerg med. 2015;33(4):600.e1-3. 31. borelli p, baldacci f, vergallo a, del dotto p, lucetti c, nuti a, et al. bilateral thalamic infarct caused by spontaneous vertebral artery dissection in pre-eclampsia with hellp syndrome: a previously unreported association. journal of stroke and cerebrovascular diseases. 2012;21(8):914. e9-. e10. 32. levy m, levy e, maimon s. atypical postpartum stroke presenting as opalski syndrome: case report and review of the literature. case reports in neurology. 2011;3(2):191-8. 33. pires c, geraldes r, neto l, melo tp. spontaneous multiple cervical artery dissection in the puerperium. cerebrovascular diseases. 2011;32(5):511-2. 34. mckinney js, messé sr, pukenas ba, satti sr, weigele jb, hurst rw, et al. intracranial vertebrobasilar artery dissection associated with postpartum angiopathy. stroke research and treatment. 2010;2010:1-5. 35. spence s, sud m, bajaj r, zavodni a, sandhu s, madan m. postpartum spontaneous coronary, vertebral, and mesenteric artery dissections: a case report. journal of medical case reports. 2016;10(1). 36. cenkowski m, dasilva m, bordun k-a, hussain f, kirkpatrick id, jassal ds. spontaneous dissection of the coronary and vertebral arteries post-partum: case report and review of the literature. bmc pregnancy and childbirth. 2012;12(1):1-4. 37. antonino m. previtera rp. vertebral artery dissection after cervical manipulation in postpartum period: a case report. congress of the italian neurological society: air.unimi.it; 2012. 38. kaplan ss, ogilvy cs, gonzalez r, gress d, pilespellman j. extracranial vertebral artery pseudoaneurysm presenting as subarachnoid hemorrhage. stroke. 1993;24(9):1397-9. 39. mitchell la, santarelli jg si, et al. reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section. j neurointervent surg. 2014;6(5). 40. sano k, kuge a, kondo r, yamaki t, homma h, saito s, et al. postpartum reversible cerebral vasoconstriction with cortical subarachnoid hemorrhage and posterior reversible encephalopathy syndrome concomitant with vertebral artery dissection diagnosed by <scp>mri msde</scp> method: a case rep. clinical case reports. 2022;10(9). 41. kelly jc, safain mg, roguski m, edlow ag, malek am. postpartum internal carotid and vertebral arterial dissections. obstetrics & gynecology. 2014;123(4):848-56. 42. gasecki ap, kwiecinski h, lyrer pa, lynch tg, baxter t. dissections after childbirth. journal of neurology. 1999;246(8):712-5. 43. shanmugalingam r, reza pour n, chuah sc, vo tm, beran r, hennessy a, et al. vertebral artery dissection in hypertensive disorders of pregnancy: a case series and literature review. bmc pregnancy and childbirth. 2016;16(1). 44. gomez-rojas o, hafeez a, gandhi n, berghea r, halalau a. bilateral vertebral artery dissection: a case report with literature review. case reports in medicine. 2020;2020:1-16. 45. monari f, busani s, imbrogno mg, neri i, girardis m, ghirardini a, et al. vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature. journal of medical case reports. 2021;15(1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. adel diab et al. 12 appendix 1: the joanna briggs institute ( jbi) critical appraisal checklist for case reports (11) study id were patient’s demographic characteristics clearly described? was the patient’s history clearly described and presented as a timeline? was the current clinical condition of the patient on presentation clearly described? were diagnostic tests or assessment methods and the results clearly described? was the intervention(s) or treatment procedure(s) clearly described? was the postintervention clinical condition clearly described? were adverse events (harms) or unanticipated events identified and described? does the case report provide takeaway lessons? total yes, (maximum = 8) nehme, 2020(23) yes yes yes yes yes yes yes yes 8 drazin, 2012(24) yes yes yes yes yes unclear no yes 6 manasewitsch, 2020(25) yes yes yes yes yes unclear unclear yes 6 monari, 2021(5) yes yes yes yes yes yes yes yes 8 drăghici, 2021(6) yes yes yes yes yes yes no yes 7 keane, 2019(26) yes yes yes yes unclear yes yes yes 7 van de kelft, 1992(27) yes yes yes yes unclear yes yes no 6 feldman, 2019(28) yes yes yes no yes yes yes yes 7 finley, 2015(9) yes yes yes yes no yes yes yes 7 nishimura, 2015(29) yes yes yes yes yes yes yes yes 8 simon, 2014(30) yes yes yes yes no yes no no 5 borelli, 2012(31) yes no yes yes unclear yes no yes 5 levey, 2011(32) yes yes yes yes yes yes yes yes 8 hutton p, 2010(14) unclear yes yes yes unclear yes no yes 5 pires, 2011(33) unclear no yes yes unclear unclear yes yes 4 mckinney, 2010(34) yes unclear yes yes yes yes yes yes 7 levy, 2011(32) yes yes yes yes yes yes yes yes 8 spence, 2016(35) yes yes yes yes yes yes yes yes 8 keane, 2019(26) yes yes yes yes yes yes yes yes 8 cenkowski, 2012(36) yes no yes yes yes yes yes yes 7 previtra, 2012(37) yes unclear yes yes yes yes yes yes 7 kaplan, 2016(38) yes yes yes yes yes unclear yes yes 7 mitchell, 2014(39) no yes yes yes yes yes yes yes 7 sano, 2021(40) yes yes yes yes no yes yes yes 7 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e26 appendix 2: the nih quality assessment tool for case series, good: met 7-9 criteria, fair: met 4-6 criteria, poor: met 0-3 criteria (12) study id was the study question or objective clearly stated? was the study population clearly and fully described, including a case definition? were the cases consecutive? were the subjects comparable? was the intervention clearly described? were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? was the length of follow-up adequate? were the statistical methods welldescribed? were the results welldescribed? total quality score quality jeannie, 2014(41) yes yes yes na yes yes yes nr yes 7 good gasecki, 1999(42) yes yes nr na no yes yes nr yes 5 fair shanmugalingam, 2016(43) yes yes no na yes yes yes nr yes 6 fair azad, 2021(19) yes yes yes yes yes no yes yes yes 8 good na: not applicable, nih: national institutes of health, nr: not reported. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations and recommendations conclusions declarations references emergency. 2017; 5 (1): e61 or i g i n a l re s e a rc h diagnostic accuracy of computed tomography scan in detection of upper gastrointestinal tract injuries following caustic ingestion hooman bahrami-motlagh1, mohammad hadizadeh-neisanghalb2, hassan peyvandi2, 3∗ 1. radiology department, loghman hakim hospital, shahid beheshti university of medical sciences, school of medicine, tehran, iran. 2. general surgery department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. hearing disorders research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: february 2017; accepted: march 2017; published online: 10 march 2017 abstract: introduction: endoscopy is an invasive procedure and finding noninvasive alternative tools in detection of probable upper gastrointestinal (gi) tract injuries following caustic ingestion is an area of interest. the present study aimed to evaluate the screening performance characteristics of thoraco-abdominal computed tomography (ct) scan in this regard. methods: this prospective cross sectional study was conducted on patients presenting to emergency department following acute caustic ingestion. the findings of ct scan and endoscopy regarding the presence of upper gi tract damage were compared and screening performance characteristics of ct scan were calculated using medcalc software. results: 34 patients with the mean age of 35.38±13.72 years were studied (58.8% male). the agreement rate between ct scan and endoscopy regarding the grade of esophageal and gastric injuries was moderate (k= 0.38; p = 0.001) and fair (k= 0.17; p = 0.038), respectively. the sensitivity and specificity of ct scan in detection of esophageal damage were 96.29) 79.1199.80) and 57.14 (20.23 88.19), respectively. these measures were 89.65 (71.50 97.28) and 40.00 (7.25 82.95), respectively for gastric damage. the area under the roc curve of ct scan in detection of esophageal and gastric damages was 0.76 (95% ci: 0.52 – 1.00) and 0.64 (95% ci: 0.35 – 0.94), respectively. conclusion: based on the findings of the present study, ct scan could be considered as a sensitive tool in ruling out upper gastrointestinal mucosal injuries following acute caustic ingestions. however, the correlation between endoscopy and ct scan findings regarding the grading of injury is not high enough to eliminate the need for endoscopy. keywords: caustics; eating; burns, chemical; tomography, x-ray computed; endoscopy © copyright (2017) shahid beheshti university of medical sciences cite this article as: bahrami-motlagh h, hadizadeh-neisanghalb m, peyvandi h. diagnostic accuracy of computed tomography scan in detection of upper gastrointestinal tract injuries following caustic ingestion. emergency. 2017; 5(1): e61. 1. introduction i ngestion of caustic substances is one of the toxicology emergencies that are associated with relatively high morbidity and mortality (1). the severity of tissue damage depends on the type, concentration, volume of ingestion, and contact duration (2, 3). the gold standard tool in assessment of mucosal damage is esophagogastroduodenoscopy (egd) within the first 12 hours of the incident (4, 5). 4 days af∗corresponding author: hassan peyvandi; hearing disorders research center, loghman hakim hospital, makhsus st., qazvin st., tehran, iran. email: hassan.peyvandi@gmail.com tel: +98-912-3260870; fax: +98-21-55416130 ter the incident, egd is not recommended due to the risk of perforation (6, 7). some believe that, egd should be performed in all patients except those who have indication of emergent surgery (6, 8, 9). however, it is an invasive procedure and there are contradicting opinions about performing endoscopy in asymptomatic patients. thoraco-abdominal computed tomography (ct) scan has been widely used in cases of caustic ingestion to gather more details about the surrounding tissues injury (10, 11). lurie et al. showed that ct scan underestimates the severity of caustic-related gastrointestinal injuries compared to egd (12). however, there is little evidence about the diagnostic accuracy of ct scan in detection of upper gastrointestinal mucosal injuries following caustic ingestion. the present study aimed to evalthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. bahrami-motlagh et al. 2 uate the screening performance characteristics of thoracoabdominal ct scan in this regard. 2. methods 2.1. study design and setting this prospective cross sectional study was conducted on patients presenting to emergency department of loghman hakim hospital, tehran, iran, in 2015, following acute caustic ingestion. all participants provided written informed consent, and the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences. researchers adhered to the helsinki recommendations throughout the study period. 2.2. participants all adult (> 15 years old) patients, presented to the emergency department of the mentioned hospital during the study period were enrolled. this hospital is the biggest poisoning center of tehran, iran capital. patients with unstable hemodynamics, third degree burns of the hypopharynx, respiratory distress, and positive history of a chronic disease or lesion in stomach or esophagus as well as those suspected to gastrointestinal perforation were excluded. 2.3. procedures upper gastrointestinal tract endoscopy was performed by expert gastroenterologists within 24 hours of admission to hospital. concurrently, thoraco-abdominal ct scan with intravenous urografin 76% contrast material was carried out for all patients. ct scan slides were reviewed by an expert radiologist who was blinded to endoscopic and clinical findings of patients. the endoscopy and ct scan grading of gastrointestinal mucosal injury were done based on appendix 1 (13, 14). 2.4. data gathering a checklist that consisted of demographic data (sex, age), type of ingested substance (acid, alkaline), volume of ingestion, duration of hospital stay, and time from event to arriving at the hospital as well as endoscopy and ct scan grading of upper gastrointestinal injuries was used for data gathering. a trained surgery resident was responsible for collection of patients’ data. 2.5. statistical analysis data were analyzed using spss version 21. continuous variables were presented as mean ± standard deviation and qualitative ones as frequency and percentage. the correlation between esophagus and stomach grading of injuries was calculated using spearman rank correlation coefficient. the inter-rater agreement between ct scan and endoscopy grading was measured using calculation of cohen’s kappa coefficient (k). k=0 defined as no agreement; 0<k≤0.2 as fair; 0.2<k≤0.45 as moderate;0.45<k≤0.75 as substantial; 0.75<k≤ 1 as almost perfect; and k=1 as perfect agreement (15). for measuring the screening performance characteristics (sensitivity, specificity, positive and negative predictive values and likelihood ratios, and area under the receiver operating characteristic (roc) curve) of ct scan in detection of gastrointestinal tract mucosal injuries following caustic ingestion, the endoscopy findings were considered as reference standard (5, 16). the endoscopy and ct scan findings were divided into normal or abnormal (with any grade of injury) groups. medcalc software version 15.0 was used for calculating the screening characteristics with 95% confidence interval (ci). p < 0.05 was considered as statistically significant. 3. results 34 patients with the mean age of 35.38±13.72 years (17 – 69) were studied (58.8% male). table 1 summarizes the baseline characteristics of studied patients. 20 (58.8%) cases were in 25 – 45 year age group and minimum and maximum volumes of caustic ingestion were 5 and 250 ml, respectively. table 2 shows the endoscopy and ct scan grading of upper gastrointestinal tract injuries. there was a significant correlation between esophagus and stomach grading of mucosal injuries based on endoscopy (r = 61.5; p = 0.001) and ct scan findings (r = 0.36; p = 0.036). the agreement between ct scan and endoscopy regarding the grade of esophageal and gastric injuries was moderate (k= 0.38; p = 0.001) and fair (k= 0.17; p = 0.038), respectively. table 3 shows the screening performance characteristics of ct scan in detection of upper gastrointestinal tract injuries following caustic ingestion. the area under the roc curve of ct scan in detection of esophagus and stomach mucosal injuries following caustic ingestion were 0.76 (95% ci: 0.52 – 1.00) and 0.64 (95% ci: 0.35 – 0.94), respectively. 4. discussion based on the findings of the present study, ct scan could be considered as a sensitive tool in screening of upper gastrointestinal mucosal injuries following caustic ingestions. in other words, ct scan could be used for ruling out mucosal injury in this setting. however, the correlation between endoscopy and ct scan findings regarding the grading of injury is not high enough to eliminate the need to perform endoscopy. currently, final decision regarding the severity of mucosal involvement of caustic ingestion is based on endoscopic findings. endoscopy is an invasive diagnostic tools and finding noninvasive alternatives for detection of probable mucosal injuries following caustic ingestion is an area of researchers’ interest. bhoil’s study showed tc99mthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e61 appendix 1: endoscopy and ct scan grading of upper gastrointestinal tract injuries endoscopic classification based on zargar’s grading system (14) grade 0 normal grade 1 superficial mucosal edema and erythema grade 2 mucosal and sub mucosal ulcerations (2a: superficial ulcerations, erosions, exudates and 2b: deep discrete or circumferential ulcerations) grade 3 transmural ulcerations with necrosis (3a: focal necrosis and 3b: extensive necrosis) grade 4 perforations computed tomography grading system (13, 19, 21) grade 1 no definite swelling grade 2 edematous wall thickening without soft tissue involvement grade 3 edematous wall thickening with soft tissue infiltration plus well-demarcated tissue interface grade 4 edematous wall thickening with soft tissue infiltration plus blurring of tissue interface or localized fluid collection around the esophagus or descending aorta table 1: baseline characteristics of studied patients variables values age (year) 15 25 7 (20.6) 25 35 10 (29.4) 35 45 10 (29.4) 45 55 2 (5.9) >= 55 5 (14.7) sex male 20(58.8) female 14(41.2) type of substance acid 30(88.2) alkaline 3(8.8) volume of ingestion (ml) 92.42 ± 89.78 hospital stay (day) 3.88 ± 2.11 time to hospital (hours) 9.69 ± 15.04 data were presented as mean ± standard deviation or frequency and percentage. pertechnetate has high agreement with egd in detection of gastric injury, but this method is not affordable and available in all health centers (17). there is little evidence regarding the accuracy of ct scan in this regard (6). some studies have mentioned various advantages of ct scan like its availability, feasibility and ability to specify the extension of extra gastrointestinal tract involvement (10, 11, 13). ct scan has been more valuable in the evaluation and approval of endoscopic gastric perforation (13, 18). ryu et al. showed that ct scan has high sensitivity and specificity in predicting complications such as esophageal stricture in patients with caustic substances ingestion (19). lurie and their colleagues assessed the role of ct scan in detecting the severity of mucosal injury due to corrosive ingestion and concluded that, decision regarding the need for surgery should not be made solely based on ct scan findings (12). in a recent review by chirica et al. 2016, ct scan was superior to endoscopy in screening of patients in need for emergent surgery (20). in this study, screening performance characteristics of ct scan for detection of esophageal and gastric injuries were about the same range. despite the high sensitivity and negative predictive value, specificity and positive predictive value of the test were not that high and therefore, this introduces ct scan as a tool for ruling out injury and not for ruling in it. the overall accuracy of the test based on area under the roc curve is poor to moderate. these findings are in line with the results of the study by lurie et al. (12). in addition to being a less invasive, easy and fast method, ct scan can give important information in the field of pulmonary infiltration and surrounding thoracic soft tissue involvement. additionally, in some situations such as upper airway inflammation, delayed visit (after 4 days and the risk of perforation), and absence of a skilled endoscopist, ct scan could be the right choice for ruling out upper gastrointestinal tract injuries. 5. limitation low sample size was one of the limitations of this study. all ct scans were interpreted by one expert radiologist, while it was better if two radiologists reviewed the ct slides and cases of disagreement were discussed with a third radiologist. 6. conclusion based on the findings of the present study, ct scan could be considered as a sensitive tool in screening upper gastrointestinal mucosal injuries following caustic ingestions. in other words, ct scan could be used for ruling out mucosal injury in this setting. however, the correlation between endoscopy and ct scan findings regarding the grading of injury is not high enough to eliminate the need to endoscopy. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. bahrami-motlagh et al. 4 table 2: endoscopy and ct scan grading of patients’ upper gastrointestinal tract injuries location grading of injuries number (%) normal i ii iii iv endoscopy esophagus 7 (20.6) 15 (44.1) 10 (29.4) 2 (5.9) 0 (0) stomach 5 (14.7) 5 (14.7) 21 (61.8) 3 (8.8) 0 (0) ct scan esophagus (proximal) 17 (50.0) 11 (32.4) 6 (17.6) 0 (0) esophagus (distal) 14 (41.2) 12 (35.3) 8 (23.5) 0 (0) stomach (fundus) 15 (41.64) 12 (35.3) 5 (14.7) 2 (5.9) stomach (body) 13 (38.2) 12 (35.3) 9 (26.5) 0 (0) stomach (antrum) 13 (38.2) 18 (52.9) 3 (8.8) 0 (0) table 3: screening performance characteristics of ct scan in detection of upper gastrointestinal tract injuries following caustic ingestion characteristics esophagus (95% ci) stomach (95% ci) true positive 26 (76.47) 26 (76.47) true negative 4 (11.76) 2 (5.88) false positive 3 (8.82) 3 (8.82) false negative 1 (2.94) 3 (8.82) sensitivity 96.29(79.1199.80) 89.65 (71.50 97.28) specificity 57.14 (20.23 88.19) 40.00 (7.25 82.95) positive predictive value 89.65 (71.5097.28) 89.65 (71.50 97.10) negative predictive value 80.00 (29.87 98.94) 40.00 (7.25 82.95) positive likelihood ratio 8.66 (2.94 25.43) 8.66 (2.94 25.43) negative likelihood ratio 0.25 (0.03 1.59) 1.50 (0.41 5.52) ci: confidence interval. 7. appendix 7.1. acknowledgements the authors would like to acknowledge the clinical research development center (crdc) of loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran, for consultation. 7.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. quingking cg, dioquino c, pascual j. predictive factors of gastrointestinal caustic injury according to clinical and endoscopic findings. asia pacific journal of medical toxicology. 2013;2(1):19-22. 2. alipour faz a, arsan f, peyvandi m, oroei m, shafagh o, yousefi m, et al. epidemiologic features and outcomes of caustic ingestions; a 10-year cross-sectional study. emergency. 2017;5(1): e56. 3. cheng h-t, cheng c-l, lin c-h, tang j-h, chu y-y, liu n-j, et al. caustic ingestion in adults: the role of endoscopic classification in predicting outcome. bmc gastroenterology. 2008;8(1):31. 4. cello jp, fogel rp, boland cr. liquid caustic ingestion spectrum of injury. archives of internal medicine. 1980;140(4):501-4. 5. mittal br, bhoil a, kashyap r, bhattacharya a, dutta u, kochhar r. 99mtc-pertechnetate scintigraphy and endoscopy in assessment of caustic-induced gastric mucosal injury. clinical nuclear medicine. 2013;38(3):e146e7. 6. bonnici k, wood d, dargan p. should computerised tomography replace endoscopy in the evaluation of symptomatic ingestion of corrosive substances? clinical toxicology. 2014;52(9):911-25. 7. tewfik t, schloss m. ingestion of lye and other corrosive agents–a study of 86 infant and child cases. the journal of otolaryngology. 1980;9(1):72-7. 8. azadegan m, ranjbar h. clinical signs and endoscopic findings of the upper gastro intestinal tract in patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e61 admitted at toxication department of loghman hakim hospital in tehran with the history of caustic substances ingestion (acid or alkaline) in 2007. pejouhandeh. 2009;14(3). 9. celik b, nadir a, sahin e, kaptanoglu m. is esophagoscopy necessary for corrosive ingestion in adults? diseases of the esophagus. 2009;22(8):638-41. 10. ananthakrishnan n, parthasarathy g, kate v. acute corrosive injuries of the stomach: a single unit experience of thirty years. isrn gastroenterology. 2010;2011. 11. keh sm, onyiioc n, mcmanus k, mcguigan j. corrosive injury to upper gastrointestinal tract: still a major surgical dilemma. world journal of gastroenterology. 2006;12(32):5223. 12. lurie y, slotky m, fischer d, shreter r, bentur y. the role of chest and abdominal computed tomography in assessing the severity of acute corrosive ingestion. clinical toxicology. 2013;51(9):834-7. 13. contini s, scarpignato c. caustic injury of the upper gastrointestinal tract: a comprehensive review. world j gastroenterol. 2013;19(25):3918-30. 14. zargar sa, kochhar r, mehta s, mehta sk. the role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. gastrointestinal endoscopy. 1991;37(2):165-9. 15. munoz sr, bangdiwala si. interpretation of kappa and b statistics measures of agreement. journal of applied statistics. 1997;24(1):105-12. 16. palao r, monge i, ruiz m, barret j. chemical burns: pathophysiology and treatment. burns. 2010;36(3):295304. 17. bhoil a, mittal b, kashyap r, bhattacharya a, kochhar r. meckel’s scan for triage in caustic injury patients: alternative to endoscopy. journal of nuclear medicine. 2012;53(supplement 1):2128-. 18. ramasamy k, gumaste vv. corrosive ingestion in adults. journal of clinical gastroenterology. 2003;37(2):119-24. 19. ryu hh, jeung kw, lee bk, uhm jh, park yh, shin mh, et al. caustic injury: can ct grading system enable prediction of esophageal stricture? clinical toxicology. 2010;48(2):137-42. 20. chirica m, bonavina l, kelly md, sarfati e, cattan p. caustic ingestion. lancet (london, england). 2016. 21. billiar t, andersen d, hunter j, brunicardi f, dunn d, pollock re. schwartz’s principles of surgery: mcgraw-hill professional; 2004. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 40 emergency (2015); 3 (1): 40-44 original research independent predictive factors of hospitalization in a north-west burn center of iran; an epidemiologic study samad shams vahdati1*, bita hazhir karzar2, negar momen2 1. road traffic injury research center, assistant professor of emergency medicine, tabriz university of medical science, tabriz, iran. 2. education development center and talented students’ office, tabriz university of medical science, tabriz, iran. *corresponding author: samad shams vahdati; assistant professor of emergency medicine, tabriz university of medical sciences, tabriz, iran. tel: +989141156941; email: sshamsv@yahoo.com; shams@tbzmed.ac.ir received: july 2014; accepted: september 2014 abstract introduction: a high-grade burn is one of the most devastating injuries with several medical, social, economic, and psychological effects. these injuries are the most common cause of accidental deaths after traffic injuries in both the developed and developing countries. therefore, this research was aimed to determine demographic characteristics of patients with burn injury admitted to the emergency department and identify predictive factors of hospitalization. methods: this is a cross sectional descriptive study, which is done in 20 march up to 20 september 2011 in emergency department of sina hospital, tabriz, iran. patients’ information including demographic characteristic, cause of burn, place of accident, anatomical areas burned, grading and percent of burning and disposition were gathered and analyzed using spss version 18.0 statistical software. stepwise multivariate regression analysis was used for recognition of independent predictive factors of hospitalization in burned patients . results: one hundred and sixty patients were enrolled (54.4% female). the average age of those was 20.47±13.5 years. the prevalence of burn was significantly higher in ages under 20 years (p<0.001). lower limb (37.5%), head and neck (21.25%) and upper limb (17.5%) were three frequent site of burn. the most common cause of burns was boiling water scalding (34.4%). home related burn was significantly higher than other place (p<0.001). the most frequent percent of burn was <5% (46.25%). finally, 50 (31.25%) cases hospitalized. univariate analysis demonstrated that age under 20 years old (p=0.02) female gender (p=0.02), burning site (p=0.002), cause (p=0.005), place (p<0.001), grade (p<0.001), and percent (p<0.001) was related to disposition of patients. stepwise multiple logistic regression showed female gender (or=3.52; 95% ci: 1.57-7.88; p=0.002), work related burning (or=1.78; 95% ci: 1.26-2.52; p=0.001), and burning over 5 percent (or=2.15; 95% ci: 1.35-3.41; p=0.001) as independent predictive factors of hospitalization. conclusion: the results of present study showed that burns injury are most frequent in age under 20 year old, lower limbs, with boiling water, and at home. in addition, the most frequent type and percentage of burned area were second degree and <5% of total body surface area, respectively. among age under 20 years old, female gender, burning site, cause, place, grade, and percent only female gender, work related burning, and burning over 5% were detected as independent predictive factors of hospitalization. key words: epidemiology; burn units; hospitalization; risk factors; emergency department cite this article as: shams vahdati s, hazhir karzar b, momen n. independent predictive factors of hospitalization in a northwest burn center of iran; an epidemiologic study. emergency. 2015;3(1):40-4. introduction: high grade burn is one of the most devastating injuries with several medical, social, economic, and psychological effects (1). these injuries are the most common cause of accidental deaths after traffic injuries in both developed and developing countries (2). the patients with widespread burning damage die, but others suffer from prolonged recoveries (3). the survived patients require various operations with a long-term hospitalization and readmission. understanding the relationship between the hostenvironment and harmful agent can help designing preventive programs (4). such injuries occur in specific geographic and demographic patterns (5, 6). in all age groups men had higher percentage of admission than women (2, 7). in some studies most of burn events appeared in children under 5 years (7, 8). home was the most common place of the events and scalding as well a mailto:sshamsv@yahoo.com mailto:shams@tbzmed.ac.ir this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 41 emergency (2015); 3 (1): 40-44 as flame the most frequent cause (2, 7-10). no burn study has yet been performed in the north-west of iran. therefore, this research was undertaken to determine demographic characteristics of patients with burn injury admitted to the emergency department of sina hospital, the burn center of north-west of iran and identify populations at increased risk. methods: this cross sectional study was done through 20 march to 20 september 2011 in the emergency department of sina hospital, tabriz, iran. sina hospital is a burning center of north-west of iran and the only burning hospital of tabriz. data of patients attending the hospital with any burn injury were collected on a checklist included: patient characteristic, cause of burn, place of accident, disposition, anatomical areas, and grading and percent of injury. burning grading was divided into i, iia, iib, iii and iv degrees (11). types of injuries included were boiling water, gas, electrical, oil, chemical and other burns were treated on an inpatient or outpatient basis in the hospital. the protocol of study was approved by ethical committee of tabriz university of medical sciences. authors were adhered to ethical principles of helsinki declaration in all parts of study. informed consent forms were fulfilled for all participants. statistical analysis data were analyzed using spss version 18.0 statistical software. descriptions of qualitative and quantitative variables were respectively performed by frequency tables and calculation of mean± standard deviation. chisquared test was used to compare qualitative variables and independent t-test for quantitative. univariate analysis was applied to evaluation of predictive factors of hospitalization. stepwise multivariate regression analysis was used for recognition of independent predictive factors of hospitalization in burned patients. statistical significance was defined as p<0.05. results: one hundred and sixty patients were enrolled (54.4% female). table 1 shows baseline characteristics of studied patients. the average age of cases was 20.47±13.5 years. most of the patients were under 20 years old (56.9%). the multinomial logistic regression showed a significant difference among burn prevalence in age groups (p<0.0001). based on this analysis, the prevalence of burn was significantly higher in ages under 20 years (p<0.001). lower limb (37.5%), head and neck (21.25%), and upper limb (17.5%) were three frequent sites of burn. lower limb burn was significantly higher than other organs (p<0.001). the most common cause of burns was boiling water scalding (34.4%), followed by hot oil (16.9%) and gas contact (16.9%) (p=0.001). seventy-three (45.6%) cases of burns occurred at home, 39 (24.4%) outdoors, and 30 (18.75%) workplace. home related burn was significantly higher than other places (p<0.001). forty-nine (30.6%) patients have first-degree of burn, 67 (41.9%) second-degree, 36 (22.5%) third degree, and 8 (5.0%) fourth-degree. multinomial logistic regression showed that the prevalence of second-degree burns were significantly higher than third degree (p=0.003) and fourth degree (p<0.001). the most frequent percentage of burn was <5% (46.25%) that is significantly more than 5-10% (p=0.009) and >10% (p=0.002). finally, 50 (31.25%) cases were hospitalized. table 2 shows the relation between disposition of patients and clinical and demographical variables. univariate analysis demonstrated that age under 20 years old (p=0.02), female gender (39.1; p=0.02), burning site (p=0.002), burning cause (p=0.005), burning place (p<0.001), grade of burning (p<0.001), and the percent of burning (p<0.001) were related to disposition of patients. stepwise multiple logistic regression showed female gender (or=3.52; table 1: the baseline variable of studied patients variable n (%) age (year) 1-10 44 (27.5) 11-20 47 (29.4) 21-30 36 (22.5) 31-40 21 (13.1) >40 12 (7.5) gender male 73 (45.6) female 87 (54.4) site of burn lower limb 60 (37.5) head and neck 34 (21.25) upper limb 28 (17.5) thoraces 25 (15.6) back trunk 7 (4.4) abdomen 6 (3.75) cause of burn boiling water 55 (34.4) oil 27 (16.9) gas 27 (16.9) electrical burning 23 (14.4) others 28 (17.5) place of injury home 73 (45.6) work 30 (18.75) out door 39 (24.4) others 18 (11.25) grade i 49 (30.6) ii 67 (41.9) iii 36 (22.5) iv 8 (5.0) percent of burn < 5% 74 (46.3) 5-10 % 45 (28.1) >10% 41 (25.6)  total body surface area this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shams vahdati et al 42 95% ci: 1.57-7.88; p=0.002), work related burning (or=1.78; 95% ci: 1.26-2.52; p=0.001), and percent of burning over 5% (or=2.15; 95% ci: 1.35-3.41; p=0.001) as independent predictive factors of hospitalization (table 3). discussion: the results of present study showed that burn injuries are more common in age less than 20 years old, in lower limbs, with boiling water, and at home. in addition, the most frequent type and percentage of burned area were second degree and <5% of total body surface area, respectively. among age under 20 years old, female gender, burning site, burning cause, burning place, grade of burning, and percent of burning only female gender, work related burning, and percentage of burning over 5% were identified as independent predictive factors of hospitalization. burns are one of the serious preventable events (12, 13). this study was the first research on burn injury in the north-west of iran. we focused on those patients who attended to the emergency department of sina hospital. the findings of present study revealed that most of burn patients were aged 20.47±13.5 years. the mean age of burn patients is different from 19 to 35 years in various studies. in most papers this age was reported between 21 and 23 years old (14). generally, young adults are active both at home and at work and this may be susceptible them to hazardous situations. most of cookers with 20-47years old are not expert, one of the reasons that this age group is more disposed to burn events. because of social structure in our country, older people usually live with their family and thus their exposure to hazardous situations has been greatly reduced. this might be explained why they have low percentage of accidents in the present study. females had higher incidence in this study as other ones (3, 15, 16) contrasts with others (17-21). it seems that some of factors such as culture and career have more effects on table 2: relation of baseline variable of studied patients and disposition variable disposition p-value discharged hospitalized age (year) 1-10 34 (77.3) 10 (22.7) 0.02 11-20 28 (59.6) 19 (40.4) 21-30 21 (58.3) 15 (41.7) 31-40 15 (71.4) 6 (28.6) >40 12 (100.0) 0 (0.0) gender male 57 (78.1) 16 (21.9) 0.02 female 53 (60.9) 34 (39.1) site of burn lower limb 44 (73.3) 16 (26.7) 0.002 head and neck 21 (61.8) 13 (38.2) upper limb 21 (75.0) 7 (25.0) thoraces 18 (72.0) 7 (28.0) back trunk 0 (0.0) 7 (100.0) abdomen 6 (100.0) 0 (0.0) cause of burn boiling water 45 (81.8) 10 (18.2) 0.004 oil 12 (44.4) 15 (55.6) gas 15 (55.6) 12 (44.4) electrical burning 16 (69.6) 7 (30.4) others 22 (78.6) 6 (21.4) place of injury home 61 (83.6) 12 (16.4) <0.001 work 13 (43.3) 17 (56.7) out door 29 (74.4) 10 (25.6) others 7 (38.9) 11 (61.1) grade i 46 (93.9) 3 (6.1) ii 33 (48.25) 34 (50.75) iii 27 (75.0) 9 (25.0) <0.001 iv 4 (50.0) 4 (50.0) percent of burn < 5% 64 (86.5) 10 (13.5) 5-10 % 21 (46.7) 24 (53.3) <0.001 >10% 25 (61.0) 16 (39.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 43 emergency (2015); 3 (1): 40-44 the gender predominance in burn injuries. home was the most common sites of burns. similar to most iranian studies (14), the highest percentage of burning place in this research was at home as well. this findings are comparable to other reports from developing countries (22, 23). in developed countries because of safer cooking devices this results are lower than developing countries. developed countries have more occupational burn events (24, 25). this study showed that the most common cause of burn is scalding like other studies (4, 7, 17, 19, 26-29) unlike other researches (2, 3, 8, 9, 3033). cooking and repairing the car radiator is more frequent cause of burning, occur with boiled water. in poor countries electricity and scalding are common causes of burn events (18). burning under 5% is more common than other types (4), dissimilar to other studies (7-9, 17). because patients are not in danger to have high grade and high percent burning illness, and of course outpatient is more frequent than disposition. in this study the most common anatomical area burned is lower limb unlike previous reports (7, 26). since using boiled water either in cooking or repairing the car radiator is in standing position, the most common burning site is lower limb. thus, for such cases it was suggested to change the life style and manage oil and heat resources of houses (34). conclusion: the results of present study showed that burns injury are most frequent in age under 20 year old, lower limbs, with boiling water, and at home. in addition, the most frequent type and percentage of burned area were second degree and <5% of total body surface area, respectively. female gender, work related burning, and percentages of burning over 5% were detected as independent predictive factors of hospitalization. acknowledgments: none. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. königová r. factors influencing survival and quality of life in burns. acta chir plast. 1995;38(4):116-8. 2. asuquo me, ekpo r, ngim o. a prospective study of burns trauma in children in the university of calabar teaching hospital, calabar, south–south nigeria. burns. 2009;35(3):433-6. 3. akther j, nerker n, reddy p, khan m, chauhan m, shahapurkar v. epidemiology of burned patients admitted in burn unit of a rural tertiary teaching hospital. pravara med rev. 2010;5:11-7. 4. feck g, baptiste ms. the epidemiology of burn injury in new york. public health rep. 1979;94(4):312-9. 5. wigglesworth e. injury control: a state-of-the-art review. aust n z j surg. 1977;47(2):248-51. 6. haddon w. energy damage and the ten countermeasure strategies. hum factors. 1973;15(4):355-66. 7. xin w, yin z, qin z, et al. characteristics of 1494 pediatric burn patients in shanghai. burns. 2006;32(5):613-8. 8. rouzbahani r, omranifard m, rouzbahani a, barkhordari m. an epidemiological study on burned patients admitted in the burn hospital in isfahan province, iran in 2002. rawal med j. 2004;29:13-7. 9. dongo ae, irekpita ee, oseghale lo, ogbebor ce, iyamu ce, onuminya je. a five-year review of burn injuries in irrua. bmc health serv res. 2007;7(1):171-7. 10. aksoy n, arli s, yigit o. a retrospective analysis of the burn injury patients records in the emergency department, an epidemiologic study. emergency. 2014;2(3):115-20. 11. tintinalli je, stapczynski js, cline dm, ma oj, cydulka rk, gd. m. tintinalli’s emergency medicine, a comprehensive study guide. 7th ed. china: mcgrew hill; 2011. p. 201-3. 12. cronin k, butler p, mchugh m, edwards g. a 1-year prospective study of burns in an irish paediatric burns unit. burns. 1996;22(3):221-4. 13. ytterstad b, søgaard a. the harstad injury prevention study: prevention of burns in small children by a communitybased intervention. burns. 1995;21(4):259-66. 14. sadeghi-bazargani h, mohammadi r. epidemiology of burns in iran during the last decade (2000–2010): review of literature and methodological considerations. burns. 2012;38(3):319-29. 15. fernández-morales e, gálvez-alcaraz l, fernándezcrehuet-navajas j, gómez-gracia e, salinas-martínez j. epidemiology of burns in málaga, spain. burns. 1997;23(4):323-32. 16. hemeda m, maher a, mabrouk a. epidemiology of burns admitted to ain shams university burns unit, cairo, egypt. burns. 2003;29(4):353-8. 17. coban yk, erkiliç a, analay h. our 18-month experience at a new burn center in gaziantep, turkey. ulus travma acil cerrahi derg. 2010;16(4):353-6. 18. haberal m, uçar u, bilgin n. epidemiological survey of table 3: independent predictive factors of hospitalization in studied patients variable odd ratio 95% confidence interval p-value female gender 3.52 1.57-7.88 0.002 work related burning 1.78 1.26-2.52 0.001 percent of burning > 5 % 2.15 1.35-3.41 0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shams vahdati et al 44 burns treated in ankara, turkey and desirable burnprevention strategies. burns. 1995;21(8):601-6. 19. tang k, jian l, qin z, zhenjiang l, gomez m, beveridge m. characteristics of burn patients at a major burn center in shanghai. burns. 2006;32(8):1037-43. 20. edlich r, glasheen w, attinger e, anne a, haynes b, hiebert j. epidemiology of serious burn injuries. surg gynecol obstet. 1982;154(4):505-9. 21. libber sm, stayton dj. childhood burns reconsidered: the child, the family, and the burn injury. j trauma. 1984;24(3):245-52. 22. el sonbaty m, el oteify m. epidemiology of burns in assiut province, egypt, during the last two years. ann burns and fire disasters. 1991;14:106-9. 23. jha ss. burns mortality in bombay. burns. 1981;8(2):11822. 24. adesunkanmi k, oyelami o. the pattern and outcome of burn injuries at wesley guild hospital, ilesha, nigeria: a review of 156 cases. j trop med hyg. 1994;97(2):108-12. 25. el-muhtaseb h, qaryoute s, ragheb sa. burn injuries in jordan: a study of 338 cases. burns. 1983;10(2):116-20. 26. khan a, rawlins j, shenton a, sharpe d. the bradford burn study: the epidemiology of burns presenting to an inner city emergency department. emerg med j. 2007;24(8):564-6. 27. mackay a, halpern j, mcloughlin e, locke j, crawford jd. a comparison of age-specific burn injury rates in five massachusetts communities. am j public health. 1979;69(11):1146-50. 28. čelko am, grivna m, dáňová j, barss p. severe childhood burns in the czech republic: risk factors and prevention. bull world health organ. 2009;87(5):374-81. 29. tung k-y, chen m-l, wang h-j, et al. a seven-year epidemiology study of 12,381 admitted burn patients in taiwan—using the internet registration system of the childhood burn foundation. burns. 2005;31(1):s12-s7. 30. lari ar, alaghehbandan r, nikui r. epidemiological study of 3341 burns patients during three years in tehran, iran. burns. 2000;26(1):49-53. 31. quayle ks, wick n, gnauck ka, schootman m, jaffe dm. description of missouri children who suffer burn injuries. inj prev. 2000;6(4):255-8. 32. lundgren rs, kramer cb, rivara fp, et al. influence of comorbidities and age on outcome following burn injury in older adults. j burn care res. 2009;30(2):307-11. 33. pavoni v, gianesello l, paparella l, buoninsegni lt, barboni e. original research outcome predictors and quality of life of severe burn patients admitted to intensive care unit. medicine. 2010;18:24-30. 34. vahdati ss, moradi n, 4:191 gj. burn in north-west of iran, prevalence of burning in east azarbaijan. emerg med. 2014;4:191-7. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 43 emergency (2014); 2 (1): 43-45 case report a young man with myocardial infarction due to trenbolone acetate; a case report kavous shahsavari nia1, farzad rahmani2*, hanieh ebrahimi bakhtavar3, yashar hashemi aghdam4, moloud balafar1 1. road traffic injury research center, tabriz university of medical sciences, tabriz, iran 2. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 3. department of emergency medicine, ardabil university of medical sciences, ardabil, iran 4. young researchers club, islamic azad university, tabriz, iran abstract over the four decades, a significant decrease has been observed in age-related mortality caused by cardiovascular disease. people in developing countries suffer from cad at a relatively younger age and about half of mi occurs under the age of fifty years. abuse of anabolic steroids is one of the less common causes of atherosclerosis. in this report, a 23-year-old body builder male referred to emergency department (ed) with myocardial infarction (mi) following chronic trenbolone acetate consumption. it seems that a comprehensive history of steroid consumption in young patients referred to ed with the chief complaint of chest pain or its equivalents is necessary in adjunct to other cardiac risk factors. key words: chest pain; anabolic agents; myocardial infarction; young adult cite this article as: shahsavari nia k, rahmani f, ebrahimi bakhtavar f, hashemi aghdam y, balafar m. a young man with myocardial infarction due to trenbolone acetate; a case report. emergency. 2014;2(1):43-5. introduction:1 oronary artery disease (cad) is a leading cause of death throughout the world (1). over the four decades, a significant decrease has been observed in age-related mortality caused by cardiovascular disease (2). people in developing countries suffer from cad at a relatively younger age and about half of mi occurs under the age of fifty years (3). inadequate perfusion due to atherosclerosis is a common cause of coronary artery stenosis (2). ischemic chest pain in young adults is usually related to hypertrophic cardiomyopathy, congenital coronary abnormalities, tachyarrhythmia, myocarditis, aortic stenosis, dissection, or coarctation (4). age, male sex, hypertension, smoking, diabetes, dyslipidemia, and obesity are considered as established risk factors for cardiovascular diseases and atherosclerosis (5, 6). abuse of anabolic steroids is one of the less common causes of atherosclerosis. these agents are used currently to increase protein synthesis and muscle growth in athletes (7). since the use of anabolic steroids has been increased, different types of them produced (8). mostly people start using the anabolic steroids in school time (9). according to the statistics, 0.9% of men and 0.1% of women use these agents during their lifetime (10). in this review, a 23-year-old male body builder was reported, with myocardial infarction (mi) following use of trenbolone acetate. *corresponding author: farzad rahmani, md. emergency medicine department, imam reza hospital, tabriz university of medical sciences, golgasht avenue, tabriz, iran. postal code: 5166614756. fax number: 00984113352078. email: farzadrhn88@gmail.com. received: 12 january 2013; accepted: 13 january 2014 case report: a 23-year-old man was referred to the emergency room with epigastric pain since the last day. he was an athlete and his previous medical history was negative. due to the absence of risk factors for heart disease, symptomatic treatment was done for him and his pain decreased so that the patient was discharged from the emergency department. but, after 3 days the patient presented again to ed with the same complaint. the pain radiated to the left arm accompanied by nausea. after obtaining the accurate history of the patient, it was elucidated that he has been using the trenbolone acetate in his daily diet since last year. the patient's vital signs were included blood pressure 130/80 mmhg, heart rate 105 per minute, respiratory rate 25 per minute, o2 sat 98% (on room air). in physical examination, the patient had sweated and the lungs were clear on auscultation. s1 and s2 sounds of heart were normal and s3 sound was heard, too. the abdomen was soft but not tender. according to the examination and history of the patient, electrocardiogram (ecg) was obtained and showed that st elevation on v1-v6 leads (figure 1). his portable chest radiograph was normal. cardiac markers (creatine kinase mb and troponin i) were elevated. due to the unavailability of a heart center for doing an emergency percutaneous coronary intervention (pci), the patient was treated with fibrinolysis (streptokinase). then, the patient was transferred to the cardiac center. he was admitted to the cardiology ward and after a week, angiography was done for him. the patient’s angiography showed the stenosis of the left anterior dec this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 44 shahsavari nia et al scending (lad) and left circumflex (lcx) arteries (figure 2). discussion: anabolic steroids can cause many problems such as cardiovascular which includes hypertension, left ventricular hypertrophy, impaired diastolic filling, polycythemia and thrombosis (7). the effects of steroids on lipid profile include decreasing in high density lipoprotein (hdl), increasing in low density lipoprotein (ldl) and total cholesterol. these changes are leaded to increase the risk of atherosclerosis in the coronary arteries (11-13). indirectly, increasing the concentrations of ldl due to the abuse of anabolic steroids may lead to an increase in sensitivity of platelets (14). long-term effects of these agents can be observed in the cardiovascular system, mental health, and increasing the risk of neoplasm (15). the mortality rate is higher in abusers of these agents (7). trenbolone acetate is a synthetic anabolic steroid (16) often referred to as "fina" by users, because the injectable trenbolone acetate was originally adapted for use by bodybuilders from the dissolution of finaplix h pellets; it is an ear implant used by cattle ranchers to maintain the weight of cattle during shipping to slaughter. trenbolone is a steroid used by veterinarians on livestock to increase muscle growth and appetite (17, 18). because these drugs have remarkable effects on bulking muscle mass and burning fats, illicit use of them have been increased among bodybuilders(18). therefore, it seems to be necessary that a comprehensive history of steroid consumption in young patients present to the emergency department with the chief complaint of chest pain or its equivalents should adjunct to other cardiac risk factors. conclusion: when young athletes with a history of anabolic drugs refer to the emergency department with complaints of chest pain, ischemic heart issues must be considered. without the necessary symptoms to exclude ischemic heart problems, lower age is not an enough criterion for such an exclusion. acknowledgments: the authors would like to express our sincere appreciation to mrs. farnoosh rahmani for scientific editing of this manuscript. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. figure 1: the 12lead patient’s electrocardiogram.  figure 2: patient’s angiography views. a) upper arrow: left anterior descending artery (lad), lower arrow: left circumflex artery (lcx); b) after percutaneous coronary intervention (pci) and stent placement in lad. references: 1. murray cj, lopez ad. mortality by cause for eight regions of the world: global burden of disease study. the lancet. 1997; 349(9061):1269-76. 2. marx ja, hockberger rs, walls rm, adams ga. concepts and clinical practice. rosen's emergency medicine. 8ed. philadelp hia, pa: elsevier saunders; 2014. p. 997-1033. 3. enas ea, senthilkumar a. coronary artery disease in asian indians: an update and review. coron artery dis. 2005;3:2157. 4. maron bj. the young competitive athlete with cardio vascular abnormalities: causes of sudden death, detection by preparticipation screening, and standards for disqualification. card electrophysiol rev. 2002;6(1):100-3. 5. balagopal pb, de ferranti sd, cook s, et al. nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth a scientific statement from the american heart association. circulation. 2011;123(23):2749-69. 6. libby p, theroux p. pathophysiology of coronary artery disease. circulation. 2005;111(25):3481-8. 7. kam p, yarrow m. anabolic steroid abuse: physiological and anaesthetic considerations. anaesthesia. 2005;60(7):685-92. 8. korkia p. use of anabolic steroids has been reported by 9% http://en.wikipedia.org/wiki/acetate http://en.wikipedia.org/wiki/implant_(medicine) http://en.wikipedia.org/wiki/steroid http://en.wikipedia.org/wiki/veterinarian this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 45 emergency (2014); 2 (1): 43-45 of men attending gymnasiums. brit med j. 1996;313(7063): 1009-14. 9. buckley we, yesalis iii ce, friedl ke, anderson wa, streit al, wright je. estimated prevalence of anabolic steroid use among male high school seniors. jama. 1988;260(23):3441-5. 10. dawson r. drugs in sport-the role of the physician. j endocrinol. 2001;170(1):55-61. 11. dickerman rd, mcconathy wj, zachariah ny. testosterone, sex hormone-binding globulin, lipoproteins, and vascular disease risk. j cardiovasc risk. 1997;4(5-6):363-6. 12. glazer g. atherogenic effects of anabolic steroids on serum lipid levels: a literature review. arch intern med. 1991;151 (10):1925-31. 13. hartgens f, rietjens g, keizer h, kuipers h, wolffenbuttel b. effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). brit j sports med. 2004;38(3):253-9. 14. rockhold r. cardiovascular toxicity of anabolic steroids. annu rev pharmacol toxicol. 1993;33(1):497-520. 15. pärssinen m, seppälä t. steroid use and long-term health risks in former athletes. sports med. 2002;32(2):83-94. 16. zarkawi m, galbraith h, hutchinson j. the action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function in the guineapig. lab anim. 1991;25(2):117-21. 17. skarberg k, nyberg f, engstrom i. multisubstance use as a feature of addiction to anabolic-androgenic steroids. eur addict res. 2009;15(2):99-106. 18. wilson vs, lambright c, ostby j, gray le, jr. in vitro and in vivo effects of 17beta-trenbolone: a feedlot effluent contaminant. toxicol sci. 2002;70(2):202-11. emergency. 2016; 4 (4): 169-170 let ter tarantula bite in iran; a letter to the editor hossein sanaei-zadeh1∗ 1. medical school, shiraz university of medical sciences, shiraz, iran. received: october 2015; accepted: november 2015 cite this article as: sanaei-zadeh h. tarantula bite in iran; a letter to the editor. emergency. 2016; 4(4):169-170. figure 1: tarantula; picture from wikipedia. dear editor i read with great interest the case report titled “periumbilical pain with radiation to both legs following tarantula bite; a case report” published in emergency journal (1). the authors introduce a male patient presenting with periumbilical pain radiating to both legs. they performed paraclinical evaluations to rule out large vessel insult and herniated disk; however, he discharged himself against medical advice and was re-admitted after 24 hours with right leg swelling and erythema. this time, several bite-like sites were detected on his leg. the authors expected the patient’s signs and symptoms to be due to the tarantula bites. it should be mentioned ∗corresponding author: hossein sanaei-zadeh; medical school, shiraz university of medical sciences, emergency room/division of medical toxicology, hazrat ali-asghar (p) hospital, meshkinfam street, 7143918796 shiraz, iran, email: sanaiezadeh@sums.ac.ir . figure 2: solifugid or rotailas as called in iran; picture from wikipedia. that to date, no study has reported the existence of tarantula species in iran, where they are mistakenly named rotails (in persian) (figure 1). tarantulas are from the theraphosidae family. they are big and hairy and as the authors mentioned since they are not dangerous, they are even considered as pets (2). tarantula spiders are not medically important except for some very limited species, which do not exist in iran. solifugae -or rotails as they are called in iranare in fact another group of animals also called camel spiders (figure 2). they are also venom-free and generally cause secondary infections in the site of their bites. thus, it seems that the patient’s signs and symptoms cannot be due to the rotail or tarantula bites. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. sanaei-zadeh 170 references 1. pouraghaei m, shams vahdati s, mashhadi i, mahmoudieh t. periumbilical pain with radiation to both legs following tarantula bite; a case report. emergency. 2015;3(3):120-1 2. de haro l, jouglard j. the dangers of pet tarantulas: experience of the marseilles poison centre. clin toxicol. 1998;36(1-2):51-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references archives of academic emergency medicine. 2023; 11(1): e54 editorial journal citation report 2023 of emergency medicine journals; new players in the impact factor ranking saeed safari1,2∗, mahmoud yousefifard3,4 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. chairman and deputy editor in chief of archives of academic emergency medicine. 3. medical physiology research center, iran university of medical sciences, tehran, iran. 4. editorial manager of archives of academic emergency medicine. received: may 2023; accepted: june 2023; published online: 26 july 2023 cite this article as: safari s, yousefifard m. journal citation report 2023 of emergency medicine journals; new players in the impact factor ranking. arch acad emerg med. 2023; 11(1): e54. https://doi.org/10.22037/aaem.v11i1.2107. commenced from 1975 and calculated based on the number of overall journal citations in a year divided by the number of citable publications in the preceding two years, journal impact factor ( jif) became a convenient and conventional proxy to appraise a journal’s trustworthiness and its scholarly impact in a given field (1). nearly a year ago, clarivate analytics promised refinements in the provision of metrics of scholarly journals of the web of science (wos) database. the 2023 edition of the annual journal citation reports ( jcr) finally debuted these appealing changes. addressing their commitment to more stringent research integrity, they inaugurated the policy to assign jif to all of their registered journals, including those indexed in the emerging source citation index (esci) and arts & humanities citation index (ahci). previously, jcr assigned jif merely to journals in the science citation index expanded (scie) or the social sciences citation index (ssci) edition of wos core collections. the expansion of jif is commended as it is a decent solution to surmount hurdles associated with a lack of a consistent tool to evaluate all scholarly journals, especially contemporary ones that have emerged from the developing world and recently launched small publishers. regarding the emergency medicine (em) category, 22 journals in the emerging sources citation index (esci) attained jif, adding up to the 32 journals of scie. for its first jif allocation, the journal “archives of academic emergency medicine” (aaem) was designated with a jif of 5.4 and acceded to the 5th position in em journals, standing after the ∗corresponding author: saeed safari; emergency department, shohadaye tajrish hospital, tajrish square, tehran, iran. email: safari266@gmail.com, tel: 009822721155, orcid: https://orcid.org/0000-0002-7407-1739. highly prestigious journals of “world journal of emergency surgery” (if:8), “resuscitation” (if:6.5), “annals of emergency medicine” (if:6.2), and “emergencias” (if:5.5) and ranked as the first em journal in asia (table 1 and 2)(2). moreover, its position would rise to 4th em journal worldwide when considering jif without self-citation of 5.0, which exempts this journal from the probable nefarious editorial policies to increase its jif bogusly (3). congruous with the jcr recommendation to adopt a multifaceted approach in appraising journals rather than solely relying on crude jif, multiple indices should be contemplated when one attempts to gauge a journal’s performance (4). the immediacy index indicates how rapidly an article is published in a jcr year, thus providing a glance at journal practices for augmenting publicity of its publication. the low rank of aaem with an immediacy index of 0.3 alludes to the indispensable role of active presence in academic social networks (e.g., linkedin, researchgate, and semantic scholar). nevertheless, caution should be exercised when comparing esci journals with senior scie counterparts in employing some parameters. for instance, the cited half-life, defined as the median age of cited articles in a jcr year, is foreseeable to be lower for the nascent esci journals compared with the mature scie journals. hence, we propose instituting a modified parameter adjusted for the journals’ date of establishment or the history of indexing in main databases to sustain an impartial ranking of journals and avert biased decisions by researchers, institutes, or publishers when evaluating a journal. finally, in order to draw attention to the potential future developments, we want to point out a consideration that might stay out of sight. during the covid-19 pandemic, the prime concern of research was to shed light on this disease’s prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. safari & m. yousefifard 2 table 1: top 10 emergency medicine journals sorted by 2022 journal impact factor journal name 2022 jif jif without self cites 2022 jci jci quartile ais quartile article influence score immediacy index cited halflife total citations citable items % of articles in citable items world journal of emergency surgery 8.0 7.6 2.41 q1 q1 1.970 1.0 4.6 3,207 57 66.67 resuscitation 6.5 5.3 1.87 q1 q1 1.913 1.5 6.7 18,032 224 90.18 annals of emergency medicine 6.2 5.9 2.30 q1 q1 2.222 1.5 11.1 13,098 92 84.78 emergencias 5.5 3.8 1.40 q1 q3 0.562 1.6 2.9 944 38 94.74 archives of academic emergency medicine 5.4 5.0 1.51 q1 q1 1.035 0.3 2.4 827 80 76.25 burns & trauma 5.3 4.8 1.70 q1 q1 1.080 1.4 3.9 1,643 54 61.11 academic emergency medicine 4.4 4.1 1.56 q1 q1 1.459 0.8 10.4 10,838 95 72.63 european journal of emergency medicine 4.4 3.2 1.03 q2 q2 0.849 1.3 6.9 2,176 45 82.22 american journal of emergency medicine 3.6 3.4 1.46 q1 q2 0.834 0.8 4.5 15,437 534 93.63 scandinavian journal of trauma resuscitation & emergency medicine 3.3 3.1 1.32 q1 q1 1.044 0.5 5.5 3,826 72 91.67 jif: journal impact factor; jci: journal citation indicator; ais: article influence score. table 2: top 10 emergency medicine journals sorted by 2022 journal impact factor journal name 5-year jif 5-year jif quartile 2022 jci jci quartile ais quartile article influence score immediacy index cited halflife total citations citable items % of articles in citable items world journal of emergency surgery 7.7 q1 2.41 q1 q1 1.970 1.0 4.6 3,207 57 66.67 burns & trauma 5.9 q1 1.70 q1 q1 1.080 1.4 3.9 1,643 54 61.11 annals of emergency medicine 5.8 q1 2.30 q1 q1 2.222 1.5 11.1 13,098 92 84.78 resuscitation 5.4 q1 1.87 q1 q1 1.913 1.5 6.7 18,032 224 90.18 archives of academic emergency medicine 4.5 n/a 1.51 q1 q1 1.035 0.3 2.4 827 80 76.25 turkish journal of emergency medicine 4.5 n/a 0.38 q3 q1 1.116 0.2 4.5 1,015 40 82.50 academic emergency medicine 4.0 q1 1.56 q1 q1 1.459 0.8 10.4 10,838 95 72.63 scandinavian journal of trauma resuscitation & emergency medicine 3.5 q1 1.32 q1 q1 1.044 0.5 5.5 3,826 72 91.67 emergency medicine journal 3.2 q1 1.20 q1 q1 1.042 0.9 8.8 6,320 83 75.90 western journal of emergency medicine 3.1 q1 1.06 q1 q1 1.023 0.6 5.1 4,170 65 96.92 jif: journal impact factor; jci: journal citation indicator; ais: article influence score; n/a: not applicable. vention, diagnosis, treatment, and prognosis. consequently, the overall number of publications and subsequent citations soared, contributing to the inevitable high if of journals during the pandemic, and the field of emergency medicine is not an exception (5). this claim is authenticated by the evident rise and subsequent piecemeal decline in the jifs of the mathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e54 jority of journals in the scie collection before and after the pandemic. as support to this assertion, one can note the ongoing decrease in the proportion of articles about covid-19 in eminent, highly cited journals such as the lancet and new england journal of medicine, which further evince the impending drop of jif for all journals in this field. ultimately, we encourage all journals’ editorial teams around the globe to apprehend the imminent fall in their jif and avert the misperception that they ought to adopt more strict criteria in assessing submissions to maintain their jif. instead, they should devise strategies such as opting for and investing in trending topics in the post-covid era and motivating other researchers to submit their valuable non-covid studies. declarations acknowledgments we kindly appreciate dr. amir mohammad tolouei and dr. shayan roshdi dizaji for their valuable input and contributions to drafting this editorial. conflict of interest none. funding none. references 1. garfield e. the history and meaning of the journal impact factor. jama. 2006;295(1):90-3. 2. web of sciences. journal citation reports 2023 [available from: https://jcr.clarivate.com/jcr/home. 3. myers pl, rohrich rj, weinstein a, chung kc. beyond the impact factor in peer-reviewed literature: what really matters. plastic and reconstructive surgery. 2022;149(2):525-8. 4. daugherty a, hegele ra, lu hs, mackman n, rader dj, weber c. web of science’s citation median metrics overcome the major constraints of the journal impact factor. arterioscler thromb vasc biol. 2022;42(4):367-71. 5. delardas o, giannos p. how covid-19 affected the journal impact factor of high impact medical journals: bibliometric analysis. j med internet res. 2022;24(12):e43089. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index declarations references archives of academic emergency medicine. 2022; 10(1): e88 or i g i n a l re s e a rc h identifying situational awareness behaviors in trauma teams; a nominal group technique study azadeh rooholamini1, roghayeh gandomkar1∗, kamal basiri2, mohammad jalili3,4, ali jafarian1,5,6 1. department of medical education, school of medicine, tehran university of medical sciences, tehran, iran. 2. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 3. health professions education research center, tehran university of medical sciences, tehran, iran. 4. department of emergency medicine, school of medicine, tehran university of medical sciences, tehran, iran. 5. department of general surgery, school of medicine, tehran university of medical sciences, tehran, iran. 6. liver transplantation research center, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. received: september 2022; accepted: october 2022; published online: 7 november 2022 abstract: introduction: situational awareness (sa), as a nontechnical human factor, is critical to the success of a trauma team. this study aimed to identify representatives of behaviors supporting (desirable) and diminishing (undesirable) sa for trauma teams while performing the initial assessment of multi-trauma patients. methods: this nominal group technique study was conducted on twenty attending physicians from various specialties affiliated with tehran university of medical sciences, who were invited to a nominal group technique meeting in 2020. participants were asked to write down their proposed behaviors in silence. subsequently, each participant shared their list with the group in a round-robin format, and clarifications were made through discussion. after categorizing the ideas, we asked participants to rate each behavior’s importance on a five-point likert scale. the consensus was defined as ≥70% agreement on a rating of 4 and 5. results: the final sa behaviors for the trauma team consisted of 29 (22 desirable and 7 undesirable) behaviors arranged in seven dimensions: resource allocation, anticipate and plan, avoid fixation errors, call for help if needed, prioritize attention, reassess patient, and shared mental model. the most important desirable and undesirable behaviors were identified in resource allocation (n=8) and avoid fixation errors (n=7) dimensions, respectively. resource allocation behaviors consist of ’checking necessary equipment’, ’allocating an alternative person(s) to do the required task if needed’, ’assigning tasks to the right person(s)’, and ’addressing each team member with a requested task’. avoid fixation errors behaviors were ’insisting on performing the procedure’, ’making decisions without considering all available information’, and ’emphasizing others’ expertise in the diagnostic process’. conclusion: the proposed team sa behaviors may be used in assessing the trauma team performance and training program to promote trauma team sa. keywords: awareness; multiple trauma; patient care team; behavior cite this article as: rooholamini a, gandomkar r, basiri k, jalili m, jafarian a. identifying situational awareness behaviors in trauma teams; a nominal group technique study. arch acad emerg med. 2022; 10(1): e88. https://doi.org/10.22037/aaem.v10i1.1826. 1. introduction trauma continues to be an important cause of morbidity and mortality worldwide (1). trauma was introduced as the leading cause of death (cod) for individuals aged 46 years and ∗corresponding author: roghayeh gandomkar; third floor, no. 57, hojatdoust st., keshavarz blvd., tehran, iran. postal code: 141669591. email: rgandomkar@tums.ac.ir, tel: 021889757, orcid: https://orcid.org/0000-00027262-6243. less between 2000 and 2010 in the us (2). on the other hand, more than 90% of injury-related deaths occur in lowand middle-income countries (3). in iran, trauma is ranked second among cods (4). although these findings are discouraging, effective teamwork and making accurate decisions in the trauma teams are significant factors in reducing the rate of preventable trauma deaths (5). non-technical human factors including leadership, communication, teamwork, and situational awareness (sa) are critical to the management of a complex trauma patient and the success of trauma teams this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rooholamini et al. 2 (6, 7). sa, in particular, seems to be necessary for decisionmaking, task management, and effective performance within the dynamic and complex situations of trauma teams (8). endsely (1995) described sa as three hierarchical levels of the "perception of the elements in the environment within a volume of time and space, the comprehension of their meaning, and a projection of their status in the near future" at the level of individuals and teams (9). individual sa refers to each team member’s awareness and understanding of the dynamic information related to the current environment and task, while team sa denotes the shared understanding of a situation among team members at one point in time that facilitates their interactions, teamwork processes, and task performance (10-15). team sa has been demonstrated to be a strong predictor of team performance in healthcare, including a multidisciplinary operating room, emergency response teams, and trauma teams (16-21). studies conducted in iran showed the importance of teamwork, barriers and facilitators, and teamwork training methods in the health care delivery system (22-28). to improve teamwork and team decision-making, challenges have been reported in communication and coordination between teammates, which emphasize the importance of cognitive and social skills in improving team performance (29-31). several studies suggested the use of different educational strategies to enhance the non-technical skills among healthcare staff members to improve teamwork (32-36). in an integrated review in 2020, hosseini et al. identified situational awareness as the most common element of teamwork in resuscitation (7). gurbanpour et al., in 2020, examined the factors affecting the situational awareness of health staff in the operating room and considered training through practical experience as the main factor in increasing the level of situational awareness (37). in iran, sa studies have been done on transportation, pilots, firefighter, shooting, etc (38-42). so far, no studies have been performed on training and assessing situational awareness in complex therapeutic environments, including trauma, in iran. walshe et al. (2021) in their review highlighted that the literature about team sa in healthcare has been mainly focused on understanding how multidisciplinary healthcare teams acquire and maintain sa or how team sa influences clinical performance and patient safety (43). there are few reports about quantifiable behaviors representing team sa in healthcare multidisciplinary teams (7). meanwhile, measurable indicators of team sa are required for precision assessment to capture the complexity of team sa. another challenge associated with sa is that it is a highly contextual concept, which makes it difficult to determine a general set of behavioral indicators to operationalize it (44, 45). team sa can be characterized as teamwork behaviors that are the product of the team’s cognitive process of evaluating the current situation. such behaviors are observable and can be assessed, practiced, and trained (10-14). o’neill et al. (2018) offered a multidimensional framework of observable behaviors of team sa for an emergency (resuscitation task) and provided evidence regarding its reliability and validity then compatibilized the framework with endsley’s three-dimensional model in the context of team effectiveness (9). the framework consisted of seven dimensions: resource allocation, anticipate and plan, avoid fixation errors, call for help if needed, prioritize attention, reassess patient, and shared mental model (46). given the importance of sa for effective trauma teams, this study aimed to identify and reach a consensus on desirable and undesirable behaviors that represent the sa for trauma teams while performing the initial assessment of multiple trauma patients. we focused on the initial assessment task since it is the first and the most critical step toward decreasing both morbidity and mortality in trauma patients (47). this study aimed to identify representatives of behaviors supporting (desirable) and diminishing (undesirable) sa for trauma teams while performing the initial assessment of multi-trauma patients. 2. methods 2.1. study design and settings this nominal group technique study was conducted on twenty attending physicians from various specialties affiliated with the tehran university of medical sciences (tums), who were invited to a nominal group technique meeting in 2020. participants were asked to write down their proposed behaviors in silence. subsequently, each participant shared their list with the group in a round-robin format, and clarifications were made through discussion. the institutional review board of tehran university of medical sciences approved the study (ir.tums.ikhc.rec.1400.302). 2.2. participants twenty attending physicians with a specialty in emergency medicine (n=5), general surgery (n=5), anesthesia (n=5), orthopedics (n=3), and neurosurgery (n=2) were invited to participate in this study if they had at least five years of experience working in trauma teams (48, 49). 2.3. data collection a nominal group technique (ngt) proposed by humphrey morto et al. (2017) was used with modifications of step four (voting) to identify and reach a consensus on the most important behaviors representing the trauma team sa during the initial assessment of a multi-trauma patient (48). participants who agreed were provided with explanations about the concept of sa and its examples at the team level as well as inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e88 formed consent form via email. the ngt meeting was conducted at one of the hospitals affiliated with tums in february 2020 and moderated by a medical education specialist (rg) and a surgery attending physician (aj). in the first step (i.e. a silent listing of items), the aim and procedures of the meeting, and a brief overview of the team sa concept was presented by one of the authors (ar). then two questions were asked about the desirable and undesirable behaviors representing team sa during the initial assessment of multiple trauma patients and participants were asked to write down their ideas, independently and silently, in response to questions without any permission to discuss their responses with others. desirable and undesirable behaviors were defined as those that support (desirable) or diminish (undesirable) trauma team sa. in the next step, these responses were shared with all participants in a round-robin format without discussion or explanation. participants were encouraged to use other participants’ responses to write down new ideas that may not have been considered in the previous round. round-robin was continued until no new information was generated. all responses were typed word by word on the word office@ 2016 (microsoft corporation, redmond, washington) by ar and displayed to the participants simultaneously using a video projector. during these steps, the number of responses was not limited and participants could list as many behaviors as they wanted. after the round-robin portion, moderators briefly discussed each proposed item for clarification in terms of ideas representing team sa for the initial assessment task and consolidating similar responses, without any judgment or criticism. since participants’ responses were mainly narrations of their experiences (instead of behaviors) and appreciating the participants’ limited time, the remainder of the meeting was performed off-site. we consequently, analyzed the narrations, qualitatively, to extract and categorize team sa behaviors. during the voting step, the classified behaviors were provided online to the participants of the ngt meeting and they were asked to rate the importance of each of the behaviors based on a five-point likert scale from five (very important) to one (not important). 2.4. data analysis we utilized qualitative and quantitative methods to analyze data collected during the ngt meeting. for qualitative analysis, the first author (ar) read and re-read the narrations and extracted the related behaviors, and then, another author (rg) reviewed the initial coding, independently. the two authors discussed extracted behaviors and agreed on them. behaviors were merged based on similarities and then grouped into dimensions using a framework previously described (46). table 1 describes each sa dimension and provides example quote(s) corresponding to extracted behaviors. behaviors and dimensions were finalized by receiving other authors’ (aj and mj) comments. during the quantitative analysis, descriptive statistics, including frequencies, means, and standard deviations were calculated using microsoft excel@ 2016 (microsoft corporation, redmond, washington) for raw data derived from the voting step. we calculated the frequency of votes for reporting the level of agreement and calculated the mean based on the number of participants as well as a measure of dispersion for reporting the importance rating of each behavior. we defined consensus as ≥70% agreement for a rating of 4 (important) and 5 (very important) (48). we used an existing validated frame (o’neill’s framework) to classify the behaviors and to examine if the domains apply to another task in an emergency. 3. results 3.1. participants table 2 presents the descriptive data of the study participants. seventeen attending physicians, who were specialists in emergency medicine, general surgery, orthopedics, and anesthesia, voluntarily participated in the three-hour ngt meeting. two invited neurosurgeons did not attend. thirteen completed the questionnaire in the voting step. fourteen (82.35%) and 10 (76.93%) participants were male in the ngt meeting and voting step, respectively. emergency medicine specialists had the highest experience working in trauma teams among participants. 3.2. team sa behaviors for initial assessment of multiple trauma patients throughout the qualitative analysis, a total of 38 behaviors (27 desirable and 11 undesirable) were categorized into the seven dimensions described above. after quantitative analysis, 29 behaviors (22 desirable behaviors and seven undesirable behaviors) in the same seven dimensions were agreed upon by ≥70% of participants. most of the desirable and undesirable behaviors were identified in resource allocation (n=8) and avoid fixation errors (n=7) dimensions, respectively. no undesirable behavior was reported for the four dimensions of resource allocation, call for help if needed, patient reassess, and a shared mental model (table 3). table 4 demonstrates the levels of agreement per behavior. further details on identified desirable and undesirable behaviors in each of the seven behavioral dimensions of team sa are described below. 3.3. resource allocation four desirable behaviors scored 100% agreement in this dimension: ’checking necessary equipment for monitoring and diagnosis’, ’allocating an alternative person(s) to do the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rooholamini et al. 4 required task if needed’, ’assigning tasks to the right person(s) with relevant expertise’, and ’addressing each team member with a requested task’. 3.4. anticipate and plan the most important desirable behaviors were ’preparing facilities and required drugs before performing the procedure’ and ’announcing clinical findings and corresponding therapeutic interventions’, which scored 100% and 92.30% agreement, respectively. the most important undesirable behavior was ’making equipment and medications available with a delay’, with 92.30% consensus. 3.5. avoid fixation errors 92.30% of the specialists agreed with two desirable behaviors ’using new data to consider other clinical findings’ and ’suggesting possible alternative diagnosis or differential diagnosis’. undesirable behaviors were ’insisting on performing the procedure of their choice when unnecessary’, ’making decisions without considering all available information’, and ’emphasizing others’ expertise in diagnostic or therapeutic actions’ with a 92.30% consensus. 3.6. call for help if needed in this dimension, the most important desirable behaviors including ’consulting the senior resident’ and ’consulting other specialties as needed’ were agreed upon by 92.30% and 76.92% of the specialists, respectively. 3.7. prioritize attention ’preventing and minimizing distractions by the team leader’ acquired 92.30% agreement as a desirable behavior. the ’direct engagement by the team leader to accomplish teammates’ tasks’ was identified as undesirable behavior with 92.3% consensus. 3.8. reassess the patient the most important desirable behavior was ’reassessing and reporting changes in patient condition’ with 100% consensus. 3.9. shared mental model the most important desirable behaviors that were identified with 84.62% consensus were ’reviewing the patient’s condition from the beginning of the trauma code’, ’reviewing all suggested and conducted measures’, and ’sharing all information and the anticipated course with team members’. 4. discussion the consensus on important desirable and undesirable behaviors representing team sa during the initial assessment of the multi-trauma patients from the perspective of attending physicians was identified. the predetermined team sa dimensions (i.e. resource allocation, anticipate and plan, avoid fixation errors, call for help if needed, prioritize attention, reassess patient, and shared mental model) proposed for resuscitation were employed so that apply to another task in an emergency. our findings support the notion of operationalization of a common core of sa dimensions for specific tasks (50). these findings indicated that the highest number of desirable and undesirable behaviors for supporting and diminishing trauma team sa were related to resource allocation and fixation errors dimensions, respectively. the main reason lies in the definition of the team. according to baker et al. (2006), the team consists of two or more individuals, who have specific roles, perform interdependent tasks, are adaptable, and share a common goal (51). therefore, the multidisciplinary trauma teams should be switching simultaneously between abcd (airway, breathing, circulation, and disability) sequences by focusing effectively on priorities in both evaluation and treatment of the critical condition under the intense time pressure (47). based on our knowledge, in teaching team sa to multidisciplinary teams, while performing a systematic task, two dimensions including resource allocation and avoid fixation errors should be considered. therefore, identifying team sa behaviors allows us to capture educational content that could then be designed to improve teamwork behaviors and reduce sa problems. fixation error can be the source of most sa errors in multidisciplinary teams, but no studies have previously presented this type of cognition error. accordingly, nikouline et al. (2021), in a systematic review of the errors in adult trauma resuscitation, reported that the well-identified behaviors in resource allocation help correct errors related to patient monitoring, team communication/dynamics, and performing procedures (52). desirable behaviors considered by specialists for the “resource allocation” dimension were mainly focused on managing the task, team composition, and crisis resources by the team leader. another study has shown the task management role in reducing the workload of leaders and team members throughout the induction of general anesthetics (53). team composition management has been demonstrated effective in forming the transactive memory system and subsequently, in improving the performance of teams (54); it has also been included as one of the organizational factors that influence trauma teamwork and facilitate the implementation of the non-technical skills (situational awareness, leadership, and teamwork) during trauma emergencies (55). finally, in crisis resource management (crm), determining a replacement person(s) due to the limited ability of other members to perform specific skills, and equipment availability (location and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e88 storage) has been indicated as an influential human factor (56, 57). for the “anticipate and plan” dimension, most of the desirable behaviors that were identified and agreed upon by experts were those with the use of verbal actions such as announcing the possible facilities and drugs, patient clinical findings, and treatment measures between team members, which are in line with parush et al.’s (2011) findings. their study identified situation-related speech acts as verbal communication behaviors (request, announcement, question, reply, etc.) that enabled sharing of information among healthcare workers in the operating room (58). the identified behavior of ’preparing facilities and required drugs’ before performing a procedure or with a delay is similar to the reported behavior in o’neill’s framework (46). this behavior with a delay may indicate a lack of implicit coordination in the presentation of the action based on shared knowledge and action anticipation and team members’ needs (58-60). desirable and undesirable behaviors for the “avoid fixation errors” dimension highlight the importance of a person’s awareness to gather information by noticing other symptoms, even if they are quite prominent, and also by understanding each other’s actions in the team and respecting the roles of other team members in team performance (61, 62). one critical feature in the behavior of the fixated person or team is a form of persistence over time that has been considered by specialists as undesirable behavior. they are consistent with de keyser and woods (1990) patterns of behavior that have been observed in cases of practitioner fixation such as “this and nothing else”, “everything but that” and “everything is ok” (63). the above behaviors are essential for excellent team performance in stressful situations and support team adaptation to sudden changes in patient status (64-66). a fixation occurs when a situation assessment or course of action has failed to revise more evidence about problems in attentional dynamics. in this dimension, attention is a critical factor that moderates situational awareness; and training in mental skills is needed to enhance attention management and reduce the impact of stress (63, 67). for the “call for help if needed” dimension, desirable behaviors were concentrated on seeking help and consultation from an experienced colleague or experts outside the team. these behaviors are one of the main factors that influence clinical practice and problem-solving strategies (68). helpseeking and consulting have been reported as backup behavior that team leaders employ for team adaptation and coordination, particularly in high-risk situations (69, 70). in “prioritizing the attention” dimension, two undesirable behaviors were found in relation to the leader being directly engaged in tasks that can be accomplished by other team members. the only agreed upon desirable behavior was in line with managing distractions, i.e. unnecessary phone calls, the presence of disabled people, etc., while maintaining calm and attentiveness as a team leader. this behavior is consistent with the results of fernandez et al. (2020) on team leadership behavior during actual trauma resuscitations (71). although resource allocation and priority attention were among the studied dimensions in this study, ’determining the team leader’ has not been identified as an important teamwork behavior, possibly, because of the senior level and high experience of the specialists in the nominal group. in the “patient reassess” dimension, desirable behaviors such as reporting or asking about patients’ status (airway, respiration, blood circulation, etc.) are similar to the reported behavior in o’neill’s framework (46). consistent with our findings, parush et al. (2011) indicated that the implicit and explicit coordination of information exchange in the form of providing situation-related information without request and obtaining the required information about the situation is in the team adaptability direction (58). fixation error has been avoided by actively reassessing the situation (63). in the shared mental model, the desirable behaviors with the highest importance are consistent with team sa mechanisms that facilitate the process of achieving shared sa among team members to similarly interpret information and support accurate anticipating of each other’s actions (72). according to mohammed et al.’s study results (2001), team members activate the implicit communication that characterizes highly effective teams by sharing the correct mental models (73). the emergency process team model of fernandez et al. (2008) indicated teamwork dynamics in three phases: planning, action, and reflecting (74). in our study, behaviors indicating the teamwork reflecting phase, including the debriefing process after the task and team performance evaluation, were not identified. behaviors representing the team sa are cognitive and behavioral processes that provide all members with sufficient information and share information about other members to achieve the team sa by knowing about each other, the team plans the work more reasonably and assigns tasks to the people who perform best. this explicitly improves coordination because team members can predict each other’s behaviors (implicit coordination) rather than simply reacting (53, 54). teaching these behaviors should be indirect and trigger selfreflection. however, lecture-based training is recommended to develop an understanding of team sa’s importance in clinical teaching and establish a knowledge foundation. team sa learning needs sufficient opportunities to experience interactions between individuals, equipment, and the environment (75). literature shows that movie-based teaching courses and practices using simulation promote visualizing concepts and engage learners in real scenarios to improve their abstract this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rooholamini et al. 6 conceptualizations and behavior in the future, respectively (76-78). in addition, reflecting upon the experiences and receiving feedback after practice can enhance knowledge integration (79). assessing and providing feedback based on observation of team sa behaviors has been addressed by the behavioral markers (46). our findings not only highlight the identified behaviors of team situational awareness in the context of trauma for practitioners, but also consider behaviors that could have delayed the diagnosis. therefore, understanding these human behaviors is essential for error reduction and improving patient safety (80). 5. limitation in the present study, participants imagined a hypothetical situation in identifying team sa behaviors that cause the loss of several behaviors in the real environment while performing the task. thus future research should consider observing teamwork in a simulated environment based on event-based scenarios that can complement this set of behaviors during the task. the absence of other team members like nurses, respiratory therapists, and technicians, as well as only senior and experienced clinicians participating in the ngt can be a factor in not identifying different behaviors from different views. this matter should be considered in future research to design team sa training based on different levels such as senior and junior clinicians. gender inequity and the lack of complete response rates are the other limitations that should be addressed in future research. 6. conclusion this study identified team sa behaviors during the initial assessment of multi-trauma patients by gaining consensus among multidisciplinary specialists. identifying and analyzing resource allocation and the avoid fixation errors can be considered the basis for training and assessing team sa in the trauma context. 7. declarations 7.1. acknowledgments we thank the faculty members who participated in the nominal group for their support and involvement in the study. we also thank tehran university of medical sciences for supporting this paper as a part of a ph.d. thesis. 7.2. financial support this study was part of a ph.d. dissertation in medical education at tehran university of medical sciences and conducted by its financial support with the number 50674-379-1-1400. 7.3. conflict of interest disclosure the authors have no potential conflicts to disclose. 7.4. authors’ contribution aj, rg, and ar, formulated the research idea. aj, rg, and ar facilitated the nominal group meeting. aj, rg, mj, kb, and ar performed the analysis and interpretation of the data. rg and ar wrote the manuscript and critically edited the draft of the paper. all authors approved the final manuscript. 7.5. ethics approval and consent to participate the institutional review board of tehran university of medical sciences approved the study (ir.tums.ikhc.rec.1400.302). references 1. james sl, castle cd, dingels zv, fox jt, hamilton eb, liu z, et al. global injury morbidity and mortality from 1990 to 2017: results from the global burden of disease study 2017. inj prev. 2020;26(suppl 2):i96-i114. 2. rhee p, joseph b, pandit v, aziz h, vercruysse g, kulvatunyou n, et al. increasing trauma deaths in the united states. ann surg. 2014;260(1):13-21. 3. world health organization. the injury chart book: a graphical overview of the global burden of injuries. department of injuries, and violence prevention. who, 2002. 4. saadat s, yousefifard m, asady h, moghadas jafari a, fayaz 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2009;14(4):595621. 81. husson n, carreira c, babo n. one shock after another; simulation can prevent fixation errors: a case report. apicare. 2019:23(4):401-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rooholamini et al. 10 table 1: describing situational awareness (sa) dimensions and examples of quotes corresponding to extracted behaviors of the trauma team sa regarding multiple trauma patients behavior dimensions examples of quotes allocate resources effective use of all team members to perform tasks as well as access to the necessary equipment “the surgery resident anxiously transfers the patient from the emergency room to the operating room before having been stabilized. a leader needs to be appointed first; then he/she assigns tasks. sometimes the neurosurgeon insists on performing a head ct scan before transferring the patient to the operating room.” “take intubation for instance. everyone can do it, but there is always a person who can do it better. it is advisable that those who are not experts leave the task to the most skilled person to avoid causing iatrogenic damages and making the situation worse.” “as soon as the trauma code is announced, all the necessary equipment (such as the airway) should be prepared before the patient enters the shock room.” “the team leader calls someone to obtain a good iv line for the patient.” “a surgical resident leaves the trauma room to resuscitate another patient coded in the ward, but other team members are unaware of this.” anticipate and plan inform team members of the patient’s leading position and potential needs and prepare for what will be needed “here are examples of what we explicitly announce to the other team members: the patient has low blood pressure so we asked for uncross-matched blood transfusions; we are going to intubate the patient; we inserted a chest tube in the left hemithorax; there is a hemothorax on the left side but we are going to obtain an imaging before we insert a chest tube; the patient’s sonographic exam is positive.” “due to heavy bleeding, it would probably be necessary to transfuse a lot of blood and fluids, so put them in the warmer.” avoid fixation errors use all information to revise the diagnosis or schedule as needed “the patient’s unresponsiveness to stimulation is attributed to the use of sedatives for an intubating patient, who later turns out to be suffering from an epidural hematoma.” “the patient in shock has several fractures in the legs and arms, the orthopedic surgeon, based on her experience, insists that these fractures are the cause of the patient’s low blood pressure. further evaluation reveals that the patient has a ruptured spleen as well. ” call for help when needed awareness of the team of the need for the necessary expertise to address the patient’s current condition and requesting the necessary help or support from other specialists “. . . .we are not sure about the result of the point of care ultrasound, and we are getting help from a radiologist.” prioritize attention with so much information simultaneously, team members decide to focus on information that will change over time. “given that several patients will be entering at the same time, the previous patients will be sent out of the trauma room so that there is enough space. . . as soon as the trauma code is announced, all people who are not directly involved in the care of the patients, including the patient’s companions are asked to leave the room. a member of the team provides the necessary information to the patient’s companions and informs them of the patient’s condition.” reassess patient awareness of team members of dynamic changes in the patient’s clinical condition to decide on diagnosis and treatment “in a previously normotensive patient, the orthopedic surgeons warn that the distal limb pulse in the broken leg is impalpable. reassessment of the vital signs reveals that the patient is at present hypotensive and that the peripheral pulses are weak or impalpable throughout the body.” shared mental model keep all team members up to date on what has happened, what is happening, and what will happen. the team leader announces that “the patient has no airway or breathing problems but is in shock, and no source of external or intra-abdominal bleeding has been found so far.” the team leader announces that “the result of the patient’s abdominal ultrasound is positive. the patient may have a pelvic fracture and posterior peritoneal bleeding.” ct: computed tomography; iv: intravenous. table 2: characteristics of studied participants specialty ngt meeting ngt voting step number (m/f) experience* number (m/f) experience* emergency medicine 5 (3/2) 12 ± 5.05 4 (2/2) 12.5 ± 5.54 surgery 5 (4/1) 9.4 ± 5.31 4 (3/1) 6.75 ± 0.43 anesthesia 5 (5/0) 10.8 ± 3.65 4 (4/0) 10.5 ± 4.03 orthopedics 2 (2/0) 9.0 ± 5.65 1 (1/0) 5.0 ± 0.00 data are presented as mean ± standard deviation. m: male; f: female; ngt: nominal group technique. *: year. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e88 table 3: numbers of team situational awareness behaviors generated and agreed upon during the nominal group technique by dimensions behavior dimensions generated behaviors agreed-upon behaviors desirable undesirable desirable undesirable allocate resources 9 2 8 0 anticipate and plan 5 3 3 2 avoid fixation errors 3 4 3 4 call for help when needed 2 0 2 0 prioritize attention 2 2 1 1 reassess patient 2 0 2 0 shared mental model 4 0 3 0 total 27 11 22 7 data are presented as number. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rooholamini et al. 12 table 4: the levels of agreement (behavior’s importance) per team situational awareness behaviors dimensions* behaviors agreement level (%) mean (sd) 1. addressing each team member with a requested task 100 4.30±0.11 2. assigning tasks to the right person(s) with relevant expertise 100 4.46 ±0.51 3. assigning tasks to the most qualified person(s) for the role 69.23 3.69 ±1.18 1 desirable 4. giving orders to the specific individual(s) if needed 78.58 4.07 ±0.64 5. allocating an alternative individual(s) to do the required task if needed 100 4.53 ±0.51 6. commanding other teammates to perform sequential actions 84.62 4.23 ±0.92 7. activating the trauma code 86.62 4.30 ±0.75 8. assessing the initial patient condition 86.62 4.30 ±0.75 9. checking necessary equipment for monitoring and diagnosis 100 4.61 ±0.50 undesirable 10. not notifying team members that one of the members is leaving 69.23 3.53 ±1.12 11. not assigning tasks to the specific individual(s) 61.54 3.53 ±0.87 12. announcing needs or treatment modalities, including patient transfer 84.62 4.07 ±0.64 13. announcing clinical findings and corresponding therapeutic interventions 92.30 4.23 ±0.59 desirable 14. preparing facilities and required drugs before performing the procedure 100 4.46 ±0.51 2 15. passing on recorded information to the others 53.85 3.76 ±0.83 16. obtaining information about the accident scene 69.23 3.76 ±0.59 17. preparing equipment and medications with a delay 92.30 4.07 ±0.75 undesirable 18. not receiving reports from ems personnel and/ or accompanying people 69.23 3.69 ±1.18 19. avoiding announcing readiness to act before performing the procedure 84.62 4.38 ±0.76 20. suggesting possible alternative diagnoses or differential diagnosis 92.30 4.30 ±0.63 desirable 21. considering inconsistent information 76.92 4.00 ±0.70 22. using new data to consider other clinical diagnoses 92.30 4.46 ±0.66 3 23. insisting and emphasizing diagnostic or therapeutic measures related to the team member’s specialty 84.62 4.07 ±0.86 undesirable 24. emphasizing other teammates’ expertise in diagnostic or therapeutic actions 92.30 4.15 ±0.55 25. making decisions without considering all available information 92.30 4.15 ±1.06 26. insisting on performing the procedure of their choice in case of unnecessary 92.30 4.53 ±0.66 desirable 27. consulting senior resident 92.30 4.53 ±0.66 4 28. consulting other specialties as needed 76.92 4.30 ±0.85 undesirable —desirable 29. preventing and minimizing distractions by the team leader 92.30 4.38 ±0.65 5 30. controlling environmental and systemic factors 69.23 3.76 ±0.83 undesirable 31. managing the multi-trauma patient by non-related activities 61.53 3.76 ±1.09 32. direct engagement to accomplish teammates’ tasks by the team leader 92.30 4.38 ±0.65 desirable 33. assessing and reporting changes in patient condition 100 4.61 ±0.50 34. enquiring about changes in patient condition 84.62 4.07 ±0.64 undesirable —— 35. reviewing patient’s condition from the beginning of the trauma code 84.62 4.30 ±0.75 7 desirable 36. reviewing all suggested and conducted measures 84.62 4.07 ±0.64 37. reviewing explicitly the differential diagnoses 69.23 3.92 ±0.75 38. sharing all information and the anticipated course with team members 84.62 4.07 ±0.64 undesirable —– *: the list of dimentions are presented in table 3. tsa: team situational awareness; sd: standard deviation; ems: emergency medical service. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e84 rev i ew art i c l e effect of virtual reality-based interventions on pain during wound care in burn patients; a systematic review and meta-analysis narges norouzkhani1, raziyeh chaghian arani2, hamidreza mehrabi3, parissa bagheri toolaroud4, pooyan ghorbani vajargah5,6, amirabbas mollaei5,6, seyed javad hosseini7, mahbobeh firooz7, atefeh falakdami5,6, poorya takasi5,6, alireza feizkhah5,8, hessamoddin saber5, haniye ghaffarzade5, ava nemalhabib5, alborz ghaffari5, joseph osuji9, mohammadreza mobayen5∗, samad karkhah5,6,10 † 1. department of medical informatics, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. student research committee, school of medicine, kashan university of medical sciences, kashan, iran. 3. student research committee, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 4. health information management research center, kashan university of medical sciences, kashan, iran. 5. burn and regenerative medicine research center, guilan university of medical sciences, rasht, iran. 6. department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 7. department of nursing, esfarayen faculty of medical sciences, esfarayen, iran. 8. department of medical physics, school of medicine, guilan university of medical sciences, rasht, iran. 9. school of nursing and midwifery, faculty of health, community, and education, mount royal university, calgary, ab, canada. 10.quchan school of nursing, mashhad university of medical sciences, mashhad, iran. received: july 2022; accepted: august 2022; published online: 24 october 2022 abstract: introduction: burn patients undergo daily painful wound care procedures, including washing, debridement, and dressing. this systematic review and meta-analysis aimed to examine the effect of virtual reality (vr)-based interventions on pain during wound care in burn patients. methods: a comprehensive systematic search was conducted on international electronic databases such as scopus, pubmed, and web of science with keywords extracted from medical subject headings such as "virtual reality", "virtual reality therapy", "virtual reality exposure therapy", "virtual reality immersion therapy", "exergaming”, “active-video gaming”, “burns”, “wound healings”, “pain”, and “pain management” from the earliest to may 6, 2022. the joanna briggs institute ( jbi) critical appraisal checklist was used to assess the quality of randomized control trials and quasi-experimental studies. results: 1,293 patients with burns were included in 30 studies, and their mean age was 22.89 (sd=7.63) years. 70.72% of the participants were male, and 67.05% were in the intervention group. this meta-analysis showed that vr significantly decreased pain severity in the intervention group compared to the control group (standard mean difference (smd): -0.70, 95%ci: -0.97 to -0.43, z=5.05, p<0.001, i2:82.0%). immersive vr intervention showed statistically significant effects in reducing pain intensity among the intervention group, compared to the control group (smd: -0.73, 95%ci: -0.97 to -0.49, z=5.88, p<0.001, i2:69.3%); however, this finding was not the same for non-immersive vr (smd: -0.62, 95%ci: -1.43 to 0.19, z=1.51, p=0.132, i2:91.2%). conclusion: it is suggested that health policymakers and managers equip burn wards with immersive vr devices to provide the basis for this intervention when caring for patients with burn wounds. keywords: virtual reality; burns; wound healing; pain; pain management; systematic review; meta-analysis cite this article as: norouzkhani n, chaghian arani r, mehrabi h, bagheri toolaroud p, ghorbani vajargah p, mollaei a, et al. effect of virtual reality-based interventions on pain during wound care in burn patients; a systematic review and meta-analysis. arch acad emerg med. 2022; 10(1): e84. https://doi.org/10.22037/aaem.v10i1.1756. ∗corresponding author: mohammadreza mobayen; burn and regenerative medicine research center, guilan university of medical sciences, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 2 1. introduction based on the latest data from the world health organization, it is estimated that approximately 11 million people suffer severe burns that require medical care each year (1). patients with severe burns suffer irreversible physical and psychological consequences. they also undergo daily painful wound care procedures, including washing, debridement, and dressing changes (2). proper burn wound management requires an accurate examination of the burn patient and appropriate treatment decisions (3-18). patients describe burn pains as excruciating, sharp, tender, or aching during wound care, which causes the patient to remain quiet and not respond verbally or even complain of pain (19). lack of adequate pain control impacts burn patients’ recovery negatively and is detrimental to the patient’s physical and mental health, confidence, and adherence to the treatment regimen. (20). pharmacological intervention, such as use of opioid analgesics, is the first method of controlling pain in burn patients (21). close monitoring of the intensity of pain, dose adjustment according to pain, and regular patient evaluation are necessary for the administration of opioids because of the different side effects and the possibility of physiological dependence or addiction (22). therefore, in addition to pharmacotherapy, it is necessary to use cognitive and behavioural approaches, such as distraction, reappraisal, information provision, relaxation training, and operant conditioning to reduce the need to use more opioids. distraction can be used in various ways, such as through illustration, music, games, and attention tasks (23). numerous theories have been proposed to explain how distraction affects the control or reduction of pain perception (24). virtual reality (vr) is innovative, and one of the novel methods used to distract patients from pain (25). vr technology, which can provide a comprehensive experience of the computer world, was originally built for gaming purposes but it now has expanded applicability in the health care industry and other sectors of the economy (26). immersion in the virtual world allows patients to be distracted from painful procedures (27). studies in the united states and europe rasht, iran. tel: +98-9125139506; +98-13-33552088; email: mohammadreza.mobayen@yahoo.com, orcid: https://orcid.org/0000-0001-93174955. † corresponding author: samad karkhah; nursing and midwifery school of shahid dr beheshti, hamidyan shahrak, shahid dr beheshti ave., rasht, guilan, iran. fax: +98-13-33550097; postal code: 41469-39841, tel: +989032598167; +98-13-33552088; email: sami.karkhah@yahoo.com, orcid: https://orcid.org/0000-0001-9193-9176. have shown that combining vr therapy and analgesics significantly reduces pain perception (28-30). the availability of inexpensive vr technology has provided a good opportunity for its use in healthcare environments (23). it is impossible to consider technology’s advantages without considering its disadvantages and side effects. major disadvantages of vr include the need to teach the patient and provider how to use it, nausea, and motion sickness (31). previous studies on the effectiveness of vr technology for reducing the pain of burn patients have reported conflicting results. a study by hoffman et al. (2019) showed that using of vr intervention significantly reduced the pain of burn wound debridement, while another study by konstantatos et al. (2009) found that vr had no effect on reducing the pain intensity during dressing change on a burn patient (25, 32). previous systematic reviews and meta-analyses had some limitations. one meta-analysis evaluated the effect of vr on pain during burn wound care procedures and excluded cross-over and parallel study designs in the analysis. the overall effect was reported in six studies (33). another meta-analysis reported the effect of fully immersive vr on pain experienced during dressing changes in hospitalized children and adolescents with severe burns based only on four studies (34). the present meta-analysis included parallel, cross-over or within-subjects studies on paediatric and adult populations to report the overall effect. comprehensive sub-group and sensitivity analyses were also conducted in the present study. this study provides a systematic review and meta-analysis of vr-based interventions for pain control in burn patients during wound care. 2. methods 2.1. study registration and reporting this systematic review and meta-analysis was performed based on the preferred reporting items for systematic reviews and meta-analysis (prisma) checklist (35). 2.2. search strategy a comprehensive systematic search was conducted on international electronic databases such as scopus, pubmed, web of science, and iranian electronic databases such as iranmedex, and scientific information database (sid) with keywords extracted from medical subject headings such as "virtual reality", "virtual reality therapy", "virtual reality exposure therapy", "virtual reality immersion therapy", "exergaming”, “active-video gaming”, “burns”, “wound healings”, “pain”, and “pain management” from the earliest to may 6, 2022. for example, the search strategy in pubmed/medline database included search terms such as ((“virtual reality”) or (“virtual realities”) or (“virtual reality therapy”) or (“virtual reality therapies”) or (“virtual realthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e84 ity exposure therapy”) or (“virtual reality immersion therapy”) or (“computer simulation”) or (“computer simulations”) or (“exergaming”) or (“multimedia”) or (“multimedium”) or (“mobile applications”) or (“mobile apps”) or (“portable software apps”) or (“computer-assisted therapy”) or (“computer-assisted therapies”) or (“active-video gaming”)) and ((“wounds”) or (“wound healings”) or (“dressing change”)) and ((“pain”) or (“pain management”)) and ((“burns”) or (“burns patients”) or (“patients”) or (“clients”)). keywords were combined with boolean operators "and" and "or". persian keywords equivalent to the mentioned words were searched in persian databases. two researchers performed the search processes, separately. this review does not include gray literature such as expert opinions, conference presentations, dissertations, research and committee reports, and ongoing research. gray literature includes articles produced in print and electronic formats but not evaluated by a commercial publisher (36). 2.3. inclusion and exclusion criteria in this review, randomized control trials (rcts) that were published in english and persian languages and utilized parallel, cross-over or within-subjects designs focusing on the effect of different vr methods on pain of burn patients during burn wound care were included. letters to the editor, case reports, conference proceedings, qualitative studies, and reviews were excluded. 2.4. study selection data management was conducted using endnote 8x software. strategies included eliminating duplicate studies, evaluating the title and abstract, and evaluating the full text of articles. the selection criteria of the studies were evaluated by two researchers, separately, based on the inclusion and exclusion criteria. disagreements between the two researchers were examined and resolved by a third researcher. finally, the resource list was evaluated manually to prevent data loss. 2.5. data extraction and quality assessment the researchers extracted information from the studies used in this systematic review and meta-analysis, including first author’s name, year of publication, location, design, sample size, type of intervention, duration of the study, duration of intervention and follow-up, male/female ratio, age, type of control group, tool characteristics, specific statistical tests, and key results of studies. the joanna briggs institute ( jbi) critical appraisal checklist was used to assess the quality of rcts and quasi-experimental studies (37). jbi assesses the internal validity, the similarity of participants of compared groups, the reliability of outcomes measured, and the appropriateness of statistical analysis of rct and quasiexperimental studies in 13 and 9 items, respectively. the quality of the studies in the systematic review and metaanalysis was evaluated by two researchers, separately, using a three-point reading range including "yes" (score 1), "no" (score 2), and "not applicable / not clear" (score 0). (38). the quality assessment levels of the studies in the jbi checklists were good (8), fair (6-7), and poor (5) (37). 2.6. statistical analysis data required for meta-analysis such as sample size of each intervention and control group, standard deviation (sd), study design (parallel, cross-over), type of intervention (immersive and non-immersive), risk of bias with jbi tool (good, fair, and poor), age group (paediatrics, adults, and both) of participants, and type of painful procedure (dressing, physiotherapy and debridement) were entered into excel software. data of studies that reported confidence interval, range, standard error and interquartile range (iqr) were converted to sd. to calculate the overall effect, the sample size, mean change and sd change were used in both intervention and control groups. the forest-plot chart reported the standard mean difference (smd) with the random-effect model (inverse-variance heterogeneity). a 95% confidence interval (ci) was used to determine the significance level (pvalue<0.05). the overall negative effect was considered an indicator of the effectiveness of the vr intervention. heterogeneity was investigated with i2 value. i2 above 50% was considered as substantial heterogeneity (39). sub-group analysis based on study design, type of intervention, risk of bias based on jbi tool, age group of participants, and type of painful procedure was performed. publication bias was checked using the funnel plot, and then egger’s and begg’s tests were used to measure the statistical significance. the trim and fill test was performed according to the significance of these two tests. sensitivity analysis was performed to determine the dependence of "overall effect size" on each study included in the meta-analysis. 3. results 3.1. study selection a total of 3,936 studies were obtained through a comprehensive search of electronic databases. after removing duplicate articles, 3,180 articles remained. 2,856 studies were deleted after reviewing the title and abstract of the articles due to inconsistencies with the purpose of the present review. 226 studies were excluded due to their non-experimental design. after evaluating the full texts of 88 studies, thirty-eight were excluded due to issues in design. in addition, twenty studies were excluded due to a lack of required information. finally, thirty studies (25, 28-30, 32, 40-64) were used in this systematic review. meta-analysis was performed on 23 rcts with parallel, cross-over or within-subjects designs. the results of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 4 another seven quasi-rcts were qualitatively reported (figure 1). 3.2. study characteristics a total of 1,293 patients with burns were included in 30 studies (25, 28-30, 32, 40-64), and their mean age was 22.89 (sd=7.63) years. 70.72% of the participants were male, and 67.05% were in the intervention group. twenty-three studies (25, 28, 30, 32, 41-50, 52-54, 56, 59, 60, 62-64) were rcts with parallel, cross-over or within-subjects designs, while seven studies (29, 40, 51, 55, 57, 58, 61) had quasi-experimental designs. of the studies in this systematic review and metaanalysis, twelve (25, 43, 47, 50-53, 55, 56, 59, 60, 62) reported the duration of the study with an average of 19.58 months. eighteen studies (25, 28-30, 32, 41-44, 46-49, 52, 55, 58, 60, 63) reported duration of intervention with an average of 18.22 minutes. of the studies in this systematic review and metaanalysis, thirteen (25, 30, 40, 42, 44, 46, 48, 49, 52, 56, 59, 62, 64) were conducted in the usa, and four (32, 41, 45, 50) in australia, two (43, 51) in the netherlands, two (54, 61) in iran, two (28, 55) in canada, two (57, 63) in egypt, two (29, 58) in the uk, one (47) in south africa, one (53) in china, and a study (60) in south korea. twenty-seven studies (25, 28-30, 32, 40-50, 52-54, 56, 57, 59-64) had a control group. eleven studies (29, 40, 45, 50, 53, 54, 57, 58, 62-64) used vas (visual analog scale), nine (25, 30, 42, 44, 46, 48, 49, 59, 61) studies grs (graph rating scale), and seven (28, 45, 50, 53, 55, 57, 62) studies utilized flacc (faces, legs, activity, cry and consolability) to measure pain in participants (table 1). 3.3. methodological quality assessment of eligible studies of the thirty studies (25, 28-30, 32, 40-64), twenty (25, 28, 29, 32, 40, 42, 43, 45, 47, 50, 52-54, 57, 59-64) had good quality, while ten studies (30, 41, 44, 46, 48, 49, 51, 55, 56, 58) had fair quality (figures 2 & 3). 3.4. effect of vr methods on pain of burn patients during wound care thirty studies (25, 28-30, 32, 40-64) in the present systematic review examined the effect of different vr methods on reducing pain during wound care in burn patients. the characteristics of the interventions in the included studies are presented in table 2. overall, the results of twenty-two studies (25, 28-30, 40-46, 48, 49, 51, 53, 57-60, 62-64) showed that different vr methods reduced pain, while one study (32) showed that it increased pain when caring for burn wounds. however, the results of seven studies (47, 50, 52, 54-56, 61) showed that different vr methods did not affect patients’ pain when caring for burn wounds. 3.5. a meta-analysis of the effect of different vr methods on reducing pain during wound care in burn patients the result of the meta-analysis demonstrated that the use of vr intervention, compared to the control group, led to a significant reduction in pain intensity (smd: -0.70, 95%ci: -0.97 to -0.43, z=5.05, p<0.001, i2:82.0%) (figure 4). the results of the subgroup analysis showed that immersive vr intervention significantly reduces pain intensity (smd: 0.73, 95%ci: -0.97 to -0.49, z=5.88, p<0.001, i2:69.3%). however, non-immersive vr intervention did not show a statistically significant effect on pain intensity (smd: -0.62, 95%ci: -1.43 to 0.19, z=1.51, p=0.132, i2:91.2%) (figure 4). the sub-group analyses showed that the included studies with different levels of bias (good and fair) significantly reduced pain intensity in the vr intervention groups. other results from sub-group analysis showed that vr intervention had significant effects on pediatrics and both age groups (pediatrics and adults); however, it was not statically significant in the adults. also, sub-group analysis indicated that vr intervention significantly reduced pain intensity in different burn procedures, such as dressing changes, wound debridement, and physical therapy. studies with parallel and cross-over designs showed that vr significantly affected intervention groups (table 3). sensitivity analysis showed that the overall effect of vr on pain severity levels did not depend on a single study (95%ci: -1.03 to -0.35). based on the visual inspection of the funnel plot, we found an asymmetry (figure 5). we did not observe any change in the overall effect size (smd: -0.62, 95%ci: -0.88 to -36). begg’s (p=0.02) and egger’s regression tests (p=0.04) indicated a significant publication bias. therefore, meta-trim with fill-andtrim method was used to correct probable publication bias. 4. discussion in the present systematic review, the effects of various vr methods were evaluated on patients’ pain when undergoing care for burn wounds. findings delineated that twenty-two interventions reduced pain and one intervention increased pain. meanwhile, seven interventions did not affect patients’ pain. a meta-analysis was performed on 23 studies with parallel and cross-over rct designs, which showed that vr intervention significantly reduced pain intensity. one of the most important outcomes for burn patients is pain relief when caring for burn wounds. pain in these patients is due to hypersensitivity of the pain pathways in the central and peripheral nervous systems (65). lack of proper pain management can provoke a reaction and arousal in the later stages of burn wound care (66-78). therefore, proper pain management is particularly important in these patients. in recent years, non-pharmacological approaches to relievthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e84 ing pain in burn patients have been considered. one of these approaches is vr, which has rare side effects (62). in the present review, various vr methods were used in addition to conventional therapies to reduce pain during wound care in burn patients. a systematic review and meta-analysis was performed by chan et al. on the clinical efficacy of vr in managing acute pain in various procedures. the chan et al. study showed that vr could effectively relieve procedural pain, but its statistical analyses had issues with heterogeneity (79). another review study examined the effect of vr interventions on procedural pain in paediatrics, which showed that vr interventions reduced pain in children more than standard care (80). a narrative review study examined the effect of vr on acute and chronic pain in adult patients. one of the topics studied in this study was the effect of vr on pain when changing dressings. this study showed that in 12 out of the eighteen studies reviewed, vr significantly reduced pain (81). another review examined vr as a pain management tool and demonstrated that vr therapy could be suitable for distracting the patient while creating painful stimuli (82). another systematic review and meta-analysis study examined the effect of vr on acute and chronic pain in adults. the results showed that vr effectively reduced acute pain in these patients. however, some studies have shown that vr can also reduces chronic pain, so more research is needed on the effect of vr on reducing chronic pain (83). another systematic review also examined the effect of interactive vr on pain perception in patients, which showed that this intervention effectively reduced pain. however, more intervention studies are needed to confirm the effectiveness of vr intervention in reducing pain (84). results of a meta-analysis based on 23 studies with parallel and cross-over rcts design showed that vr intervention significantly reduced pain intensity. the results of the present study were consistent with the results of previous metaanalyses. one meta-analysis (2022) was performed with six studies to evaluate the effects of vr on pain intensity and other outcomes. sub-group analysis results of this particular study showed that immersive vr (4 studies) significantly decreased pain intensity, and non-immersive vr (2 studies) had no effect on patients’ pain perception (33). based on the results of the current meta-analysis, immersive vr intervention (18 studies) significantly decreased pain intensity in the intervention group. however, non-immersive vr (7 studies) did not cause a statistically significant difference between intervention and control groups. in the non-immersive vr technique, the least interactive activities, such as interaction with the keyboards and mice without fully immersing into the environment, occurred. in immersive vr, the interaction is the highest and subjects are fully immersed in and interact with the vr environment (85). the current meta-analysis showed that vr intervention had a statistically significant effect on pediatric patients; however, it was ineffective among the adult age group. various factors, such as different contextual factors in pain perception in each age group and measurement scales, can affect pain intensity. also, one metaanalysis on paediatrics revealed that immersive vr significantly decreased pain intensity (34). future studies should compare vr effects on adults and paediatrics. the present systematic review results showed that out of thirty vr interventions, twenty-two interventions reduced patients’ pain during burn wound care procedures. the meta-analysis found that vr can statistically decrease pain intensity in the intervention group compared to the control group. according to the results of previous studies and the present systematic review and meta-analysis, it is suggested that health policymakers and managers consider equipping burn wards/units with vr devices to provide the basis for this intervention when caring for burn patients. to compare the effects of vr intervention among different age groups and immersive vs non-immersive vr, it is recommended that future research be focused on this area. 5. limitations there are limitations in this study that are noteworthy. this systematic review and meta-analysis is based on the prisma checklist but is not listed in the international prospective register of systematic reviews database (prospero). although two researchers completed the search of electronic databases, all studies on this subject may not have been found. finally, only studies in english and persian have been included, and studies in other languages have not been included. 6. implications for health managers and policymakers considering the importance of pain management when caring for burn patients using various interventions, including vr methods, and also considering the results of this systematic review and meta-analysis, it is suggested that health policymakers and managers equip burn wards with vr devices to provide the basis for this intervention when caring for the wounds of these patients, as well as develop policies and guidelines regarding the use and deployment of vr technology in the management of pain in burn patients. 7. implications for future research in the results of this meta-analysis study, studies that applied the immersive vr or performed on pediatric patients showed a more significant effect on the intervention than the control group. however, studies that applied non-immersive vr or included adults; demonstrated no significant difference bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 6 tween intervention and control groups. therefore, it is suggested that future studies focus on comparing immersive and non-immersive vr interventions in paediatrics with adults. 8. conclusion in the present systematic review, the effects of various vr methods were evaluated on patients’ pain when undergoing care for burn wounds, which showed that immersive vr intervention significantly decreased pain intensity in the intervention group. health policymakers and managers should equip burn wards with immersive vr devices to provide the basis for this intervention when caring for these patients’ wounds. 9. declarations 9.1. acknowledgments none. 9.2. authors’ contributions study concept and design by all authors; 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simmonds m. use of virtual reality (immersive vs. non immersive) for pain management in children and adults: a systematic review of evidence from randomized controlled trials. euro j exp bio. 2012;2:1408-22. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 10 figure 1: flow diagram of the study selection process. figure 2: methodological quality assessment of rct studies using joanna briggs institute ( jbi) checklist. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e84 figure 3: methodological quality assessment of quasi-experimental studies using joanna briggs institute ( jbi) checklist. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 12 figure 4: sub-group analysis based on immersive and non-immersive vr intervention. smd: standard mean difference; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2022; 10(1): e84 figure 5: funnel plot for asymmetry evaluation in included studies. smd: standard mean difference. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 14 table 1: basic characteristics of the studies included in this systematic review and meta-analysis first author/year location study characteristics 1. design 2. sample size (i/c) 3. intervention 4. duration of study 5. duration of intervention 6. duration of follow-up m/f ratio (%) age (mean±sd) control group tool characteristics 1. name of the questionnaire 2. number of items 3. overall scoring of items intervention type key results jbi score hoffman et al., 2001 (40) usa 1. quasiexperimental 2. 7 3. vr 4. n/a 5. n/a 6. 3 days 85.71/14.29 21.90 all participants served as their own control when had not received vr distraction. 1. vas 2. 100 3. 0 to 100 immersive the mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (p< 0.010). good das et al., 2005 (41) australia 1. rct (crossover) 2. 7 3. vr 4. n/a 5. 27.5 minutes 6. 0 n/a 11.10 (sd=3.50) all participants served as their own control when had not received vr. 1. face scale 2. 10 3. 0 to 10 immersive the mean score of pain in patients was decreased after the intervention in the intervention group compared to the control group (p<0.01). fair sharar et al., 2007 (42) usa 1. rct 2. 234 (88/146) 3. vr 4. n/a 5. 15 minutes 6. 0 82.91/17.09 n/a participants in the control group had not received vr. 1. grs 2. 100 mm 3. 0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good van twillert et al., 2007 (43) netherland 1. rct 2. 19 3. vr 4. 13 months 5. 19.2 minutes 6. 2 days 63.16/36.84 30.00 all participants served as their own control when had not received vr. 1. vat 2. 100 mm 3. 0 to 100 immersive the mean score of pain in participants was decreased during and a day after the intervention in the intervention group compared to the control group (p<0.05). good hoffman et al., 2008 (44) usa 1. rct (crossover) 2. 11 3. vr 4. n/a 5. 3 minutes 6. n/a 100/0 27.00 all participants served as their own control when had not received vr. 1. grs 2. 10 cm 3. 0 to 10 immersive the mean score of pain in patients was decreased during the intervention in the intervention group compared to the control group (p=0.015). fair mott et al., 2008 (45) australia 1. rct 2. 42 (20/22) 3. ar 4. n/a 5. n/a 6. 0 69.05/30.95 n/a participants in the control group had not received the ar. 1. flacc pain assessment tool 2. 5 items 3. 0 to 10 1. fps-r 2. n/a 3. n/a 1. vas 2. 5 cm 3. 0 to 5 nonimmersive the mean score of pain in participants (long dressing times) was decreased during the intervention in the intervention group compared to the control group (p=0.006). good this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2022; 10(1): e84 table 1: basic characteristics of the studies included in this systematic review and meta-analysis carrougher et al., 2009 (46) usa 1. rct (crossover) 2. 39 3. vr 4. n/a 5. 10 minutes 6. 0 89.74/10.26 35.00 (sd=11.00) participants in the control group had not received vr. 1. grs 2.100 mm 3.0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p=0.004). fair konstantatos et al., 2009 (32) australia 1. rct 2. 86 (43/43) 3. vr 4. n/a 5. 18 minutes 6. 0 n/a 38.60 (sd=15.95) participants in the control group had not received vr. 1. bsar 2.10 cm 3.0 to 10 nonimmersive the mean score of pain in participants was increased during and after the intervention in the intervention group compared to the control group (p<0.05). good morris et al., 2010 (47) south africa 1. rct (crossover) 2. 11 3. vr 4. 4 months 5. 18 minutes 6. 0 n/a n/a all participants served as their own control when had not received vr. 1.nprs 2.n/a 3.n/a 1.bspas 2.100 mm 3.0 to 100 nonimmersive there was no significant difference in pain scores during the intervention between the intervention and control groups (p=0.13). good maani et al., 2011 (48) usa 1. rct (crossover) 2. 12 3. vr 4. n/a 5. 12 minutes 6. 0 100/0 n/a all participants served as their own control when had not received vr. 1. grs 2.100 mm 3.0 to 100 immersive the mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (p<0.05). fair schmitt et al., 2011 (49) usa 1. rct (crossover) 2. 54 3. vr 4. n/a 5. 6.5 minutes 6. 0 81.48/18.52 12.00 (sd= 3.90) all participants served as their own control when had not received vr. 1. grs 2.100 mm 3.0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p< 0.05). fair kipping et al., 2012 (50) australia 1. rct 2. 41 (20/21) 3. vr 4. 15 months 5. n/a 6. 0 68.29/31.71 13.05 (sd=1.55) participants in the control group had not received the vr. 1. flacc pain assessment tool 2.5 items 3. 0 to 10 1. vas 2.10 cm 3. 0 to 10 immersive there was no significant difference between the intervention and the control group in pain score during dressing removal and application (p>0.05). good faber et al., 2013 (51) netherlands 1. quasiexperimental 2. 36 3. vr 4. 40 months 5. n/a 6. 7 days 83.33/16.67 27.70 (sd=15.20) n/a 1. vat 2.10 cm 3.0 to 10 immersive the mean score of pain in participants was decreased during the intervention on days one, two, and three (p< 0.05). fair jeffs et al., 2014 (52) usa 1. rct 2. 28 (18/10) 3. vr 4. 22 months 5. 52.5 minutes 6. 0 32.14/67.86 13.50 (sd=2.30) participants in the control group had not received the vr. 1.appt 2.115 mm 3.0 to 115 immersive there was no significant difference in pain scores between the intervention and control groups during the intervention (p=0.32). good this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 16 table 1: basic characteristics of the studies included in this systematic review and meta-analysis hua et al., 2015 (53) china 1. rct 2. 65 (33/32) 3. vr 4. 12 months 5. n/a 6. 0 47.69/52.31 8.72 (sd=3.38) participants in the control group had not perceived the vr. 1. faces picture scale 2.10 items 3.0 to 10 1. flacc pain assessment tool 2.5 items 3. 0 to 10 1. vas 2.10 cm 3. 0 to 10 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good ebrahimi et al., 2017 (54) iran 1. rct 2. 60 (40/20) 3. vr 4. n/a 5. n/a 6. 5 days 56.67/43.33 35.00 (sd=10.00) participants in the control group had not received the vr. 1. vas 2.10 cm 3.0 to 10 nonimmersive there was no significant difference in pain scores before and after the intervention between intervention and control groups from day one to five (p>0.05). good khadra et al., 2018 (55) canada 1. quasiexperimental 2. 15 3. vr 4. 7 months 5. 18.4 minutes 6. 0 40.00/60.00 2.20 (sd=2.10) n/a 1. flacc pain assessment tool 2.5 items 3. 0 to 10 nonimmersive there was no significant difference in pain scores before and after the intervention in the intervention group (p>0.05). fair mcsherry et al., 2018 (56) usa 1. rct (crossover) 2. 18 3. vr 4. 29 months 5. n/a 6. 0 72.22/27.78 38.40 (sd=15.50) all participants served as their own control when had not received vr. 1. vns 2.10 cm 3.0 to 10 immersive there was no significant difference in pain intensity between intervention and control groups after intervention (p>0.05). fair soltani et al., 2018 (30) usa 1. rct (crossover) 2. 39 3. vr 4. n/a 5. 6 minutes 6. 0 n/a 36.00 all participants served as their own control when performing rom exercises without vr distraction. 1. grs 2.100 mm 3.0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p< 0.005). fair fatma & ghada, 2019 (57) egypt 1. quasiexperimental 2. 60 (30/30) 3. vr 4. n/a 5. n/a 6. 0 60.00/40.00 n/a participants in the control group had not received vr. 1. faces picture scale 2.10 items 3.0 to 10 1. flacc pain assessment tool 2.5 items 3. 0 to 10 1. vas 2.10 cm 3. 0 to 10 immersive the mean score of pain in participants was decreased during and after the intervention in the intervention group compared to the control group (p<0.001). good hoffman et al., 2019 (25) usa 1. rct 2. 48 3. vr 4. 35 months 5. 5 minutes 6. n/a 70.83/29.17 12.00 all participants served as their own control when had not received vr. 1. grs 2.10 cm 3.0 to 10 immersive the mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (p<0.001). good this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2022; 10(1): e84 table 1: basic characteristics of the studies included in this systematic review and meta-analysis phelan et al., 2019 (58) uk 1. quasiexperimental 2. 15 3. vr 4. n/a 5. 5 minutes 6. 0 66.67/33.33 25.00 n/a 1. vas 2.100 3.0 to 100 immersive and nonimmersive • the pain threshold time was increased after the intervention in participants (p=0.003). • the pain tolerance time was increased after intervention in participants (p<0.001). • the pain tolerance time was significantly different between vr scenarios in participants (p<0.05). • the mean score of maximum pain in participants was significantly different in vr scenarios (p=0.002). fair hoffman et al., 2020 (59) usa 1. rct 2. 50 3. vr 4. 29 months 5. n/a 6. 10 days 84.00/16.00 n/a participants in the control group had not received vr. 1. grs 2.10 cm 3. 0 to 10 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good joo et al., 2020 (60) south korea 1. rct 2. 57 (28/29) 3. vr 4. 4 months 5. 30 minutes 6. 0 94.74/5.26 44.88 (sd=11.09) participants in the control group had not received vr. 1. mhq 2. n/a 3.0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p=0.002). good khadra et al., 2020 (28) canada 1. rct 2. 38 3. vr 4. n/a 5. 25 minutes 6. 0 71.05/28.95 1.82 (sd=1.32) all participants served as their own control when had not received vr. 1. flacc 2.5 items 3.0 to 10 1. nrs-obs 2.n/a 3.n/a nonimmersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good kiani et al., 2020 (61) iran 1. quasiexperimental 2. 45 (30/15) 3. vr 4. n/a 5. n/a 6. 0 n/a 31.38 (sd=8.47) participants in the control group had not received vr. 1. grs 2.100 mm 3.0 to 100 1.bspas 2.100 mm 3.0 to 100 immersive there was no significant difference in pain intensity between intervention and control groups during the intervention (p>0.05). good phelan et al., 2021 (29) uk 1. quasiexperimental 2. 20 (15/5) 3. vr 4. n/a 5. 36.9 minutes 6. 0 60.00/40.00 48.20 (sd= 19.68) participants in the control group had not received the vr. 1. vas 2.100 mm 3.0 to 100 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p= 0.007). good this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 18 table 1: basic characteristics of the studies included in this systematic review and meta-analysis xiang et al., 2021 (62) usa 1. rct 2. 90 (61/29) 3. vr 4. 25 months 5. n/a 6. 0 50.00/50.00 11.30 participants in the control group had not received the vr. 1. vas 2.100 3.0 to 100 1. flacc 2.5 items 3.0 to 10 immersive and nonimmersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good ali et al., 2022 (63) egypt 1. rct 2. 22 (11/11) 3. vr 4. n/a 5. 20 minutes 6. 0 59.09/40.91 13.18 (sd=1.73) participants in the control group had not received the vr. 1. vas 2.10 cm 3.0 to 10 immersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.001). good armstrong et al., 2022 (64) usa 1. rct 2. 24 (11/13) 3. vr 4. n/a 5. n/a 6. 7 days 79.17/20.83 11.50 (sd=3.10) participants in the control group had not received the vr. 1. vas 2.10 cm 3.0 to 10 nonimmersive the mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (p<0.05). good rct: randomized clinical trial; anova: analysis of variance; vas: visual analog scale; vr: virtual reality; ar: augmented reality; flacc: faces, legs, activity, cry and consolability; fps-r: faces pain scale-revised; grs: graph rating scale; vrpat: virtual reality pain alleviation tool; bsar: burns specific anxiety rating; vns: verbal numeric scale; mhq: michigan hand outcomes questionnaire; bspas: burn specific pain anxiety scale; appt: adolescent pediatric pain tool; nprs: numeric pain rating scale; vat: visual analog thermometer; nrs-obs: numeric rating scale-observational; n/a: not applicable; sd: standard deviation; jbi: joanna briggs institute; rom: range of motion. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 19 archives of academic emergency medicine. 2022; 10(1): e84 table 2: interventions of the studies included in the systematic review and meta-analysis first author/year intervention program description hoffman et al., 2001 (40) vr participants received vr distraction. the intervention was as follows: patients underwent active-assisted physical therapy exercises with a vr helmet. a motion-sensing system was used with a vr helmet to measure the position of the participant’s head. the first participant was placed in the virtual environment of the spider world where she/he could move virtual objects with her/his cyber hands. other participants were placed in the snow world where they could move and throw snowballs. the pain was measured via vas during the intervention. das et al., 2005 (41) vr participants received 10 to 45 minutes of vr. the intervention was as follows: coin toss was used to sequence the analgesic test using medication or using medication and vr. the content in vr was a game based on the age group of the participants. participants could shoot monsters using a pointer. the game was designed so that participants could play with minimal movement during dressing changes. the pain was measured via the face scale immediately after the intervention. sharar et al., 2007 (42) vr participants received immersive vr distraction for 15 minutes during physical therapy. the vr intervention was such that using a large screen above the patient’s head with sound effects and moving explosions of blue, white, and green, the patient’s communication with the environment was blocked. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via the grs immediately after the intervention. van twillert et al., 2007 (43) vr participants received 19.2 minutes of vr during wound dressing change. vr intervention consisted of a pair of 3d glasses and an integrated audio system. the snow world content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the mouse and keyboard. there were special effects such as river and sky along with sound effects in this intervention. the pain was measured via the vat one day before, during, and after wound dressing. hoffman et al., 2008 (44) vr participants received 3 minutes of vr distraction. the intervention was as follows: patients underwent wound debridement for three minutes with a vr waterproof cap. in immersive vr intervention, helmets, headphones, and joysticks were used to control the movement of snowballs and their launch. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via grs during the intervention. mott et al., 2008 (45) ar participants received ar during dressing change. ar is a device that has several sculptures on top of it and is lifted by a camera, creating a three-dimensional character called hospital harry. a voice or the child’s parents encouraged the child to continue and change the animation. by manipulating the camera, the child can visualize the existing character from different angles. the pain was measured via the flacc pain assessment tool, the fps-r, and the vas before, during, and after the intervention. carrougher et al., 2009 (46) vr participants received vr during physical therapy for 10 minutes. vr intervention consisted of a pair of 3d glasses and an integrated audio system. the snow world content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the mouse and keyboard. there were special effects such as river and sky along with sound effects in this intervention. the pain was measured via grs immediately after the intervention. konstantatos et al., 2009 (32) vr participants received vr relaxation with intravenous morphine patient-controlled analgesia during dressing change. vr relaxation intervention includes vr glasses, a headset, a dvd player, and a relaxing dvd. the content of the dvd includes the sequence "snow world", which is based on the theory of hypnotherapy. the program includes videos of soothing scenery that end with a spiral, and participants are asked to focus on the spiral. the pain was measured via the bsar before, during, and after the intervention. morris et al., 2010 (47) vr participants received a low-cost vr system with analgesia during physiotherapy for 18 minutes. the order of the meetings was determined using a coin toss. low-cost vr system intervention used a vr display on the patient’s head and contained a game called "walt disney’s chicken little". the pain was measured via the bspas, and nprs by a blinded assessor during physiotherapy. maani et al., 2011 (48) vr participants received robot-like arm-mounted vr goggles during wound care for 12 minutes. a random number generator was used to determine the order of intervention. the vr intervention consisted of a vr glass, a spectacle holding system, and a custom robot-like arm. the snow world content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the arm. there were special effects such as river and sky along with sound effects in this intervention. the pain was measured via the grs during wound care. schmitt et al., 2011 (49) vr participants received 3-10 minutes of vr distraction during physical therapy. the intervention was as follows: patients underwent post-burn physical therapy with a vr helmet. a motion-sensing system was used with a vr helmet to measure the position of the participant’s head. the participants were placed in the virtual environment of the snow world where they could move and throw snowballs. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via grs immediately after the intervention. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 20 table 2: interventions of the studies included in the systematic review and meta-analysis first author/year intervention program description kipping et al., 2012 (50) vr participants received an off-the-shelf vr system during dressing removal and application. the intervention was performed using a vr display on the head with a tracker and manual joystick control. the vr content displayed for patients was “chicken little” and “need for speed” games. the pain was measured via the flacc pain assessment tool and the vas before and during the intervention. faber et al., 2013 (51) vr participants received vr distraction in daily wound care. the intervention was as follows: patients underwent wound care with a vr helmet. motion-sensing system and integrated audio system were used with a vr helmet to place participants in the virtual environment of the snow world where they could move and throw snowballs. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via vat during and after interventions. jeffs et al., 2014 (52) vr participants received vr distraction during burn wound care. vr distraction intervention was performed using a vr helmet, a tripod with a hinged arm, headphones, and interaction with a trackball. the vr content of the game was snow world. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via the vas during the intervention. hua et al., 2015 (53) vr participants received vr distractions during dressing changes. vr distractions intervention was performed using a vr headset and headphones. the content of vr distraction was a third-person game called ice age 2: the meltdown, in which participants control the game character in a snowy environment to reach the oak. the pain was measured via the flacc pain assessment tool, the faces picture scale, and the vas before, during, and after the intervention. ebrahimi et al., 2017 (54) vr participants received vr for five days during dressing changes. the vr intervention was performed with a vr goggle and headset through which audio and video were streamed. the pain was measured via the vas. khadra et al., 2018 (55) vr participants received a vr dome environment during hydrotherapy for a mean of 18.4 minutes. the vr dome intervention consists of a curved plate located at the end of the hydrotherapy reservoir. the content of this intervention includes a game called bubbles in which there is a mouse and the child presses it to produce bubbles. also, animals appear on the screen, which produce funny sounds and emoticons and the child is inside a wagon that passes between/through them. the pain was measured via the flacc pain assessment tool, one hour before, immediately before, 10 minutes after onset, immediately after, and 30 minutes after hydrotherapy. mcsherry et al., 2018 (56) vr participants received immersive vr during dressing changes. the vr intervention was such that using a large screen above the patient’s head with sound effects and moving explosions of blue, white, and green, the patient’s communication with the environment was blocked. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via the vns before and after the intervention. soltani et al., 2018 (30) vr participants received 3 minutes of vr distraction. the intervention was as follows: patients underwent active physical therapy exercises with vr goggles. participants were randomly divided into two groups with/without vr treatment orders. the participants were placed in the virtual environment of the snow world where they could move and throw snowballs. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via grs immediately after the intervention. fatma & ghada, 2019 (57) vr participants received vr technology during dressing change. vr technology intervention involves a mobile phone with a 3d animation that sits on a device with 3d glasses on the head that also has headphones. the pain was measured via the flacc pain assessment tool, the faces picture scale, and the vas before, during, and after the intervention. hoffman et al., 2019 (25) vr participants received 5 minutes of vr distraction during wound cleaning. the intervention was as follows: patients underwent wound care with waterproof vr goggles that were fixed near their eyes. participants were randomly divided into two groups with/without vr treatment orders. the participants explored the virtual environment of the snow world, with a mouse, where they could move and throw snowballs. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via grs during the intervention. phelan et al., 2019 (58) vr participants received four different vr scenarios, each lasting an average of 5 minutes. the four vr scenarios were as follows: • henry scenario: a passive scenario based on a hedgehog’s birthday party. • flocker: an active scenario in which the participant is tasked with collecting sheep using special obstacles. • blindness: it was a passive scenario based on the story of a blind person. • basket: it was an active scenario in which the participant received a variety of feedback based on entering the ball into the basketball hoop. pain experienced by participants was measured using a cold compressor test that included a 4 °c cold water tank. the pain was measured via the vas. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 21 archives of academic emergency medicine. 2022; 10(1): e84 table 2: interventions of the studies included in the systematic review and meta-analysis first author/year intervention program description hoffman et al., 2020 (59) vr participants received vr distraction during wound debridement. the intervention was as follows: patients underwent wound care with waterproof vr goggles that were fixed near their eyes. the participants explored the virtual environment of the snow world, with a mouse, where they could move and throw snowballs. the snow world content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. the pain was measured via grs after the intervention. joo et al., 2020 (60) vr participants received vr-based rehabilitation for 30 minutes. the intervention involved using a system called rapael smart glove, which was a combination of a glove and a vr system. this system collects the patient’s active movements with gloves. the training program in using this glove included the following: • pronation and supination of the forearm • bending and stretching of the wrist • radial deviation and ulnar of the wrist • bending and stretching of the fingers patient pain was measured via using visual and auditory feedback and also measured based on mhq using a squeeze dynamometer. khadra et al., 2020 (28) vr participants received 10 minutes of vr distraction during hydrotherapy. the intervention was as follows: patients underwent wound care in the hydrotherapy tank with projector-based hybrid vr. participants were randomly divided into two groups with/without vr treatment orders. the participants played the bubbles video game with a mouse or automatic mode. patient pain was measured via flacc scale and nrs at the following times: t1: before the intervention, t2: first 5 minutes of intervention, t3: end of the first phase of wound care session, t4: end of the second phase of wound care session, and t5: 30 minutes after end of wound care session. kiani et al., 2020 (61) vr participants received vr. the vr intervention consisted of vr glasses with a helmet that had two speakers inside the helmet to hear the sound, as well as gloves with a sensor. to detect the movement of the head, there was a tracker sensor inside the helmet that signaled the participants’ movements to the computer. the content of this intervention included a game that had a cold and snowy atmosphere and the user threw snowballs at the snowmen to get points. the pain was measured via the grs and bspas before and after the intervention. phelan et al., 2021 (29) participants received four different vr scenarios. in this intervention, an oculus rift vr display system on the patient’s head, a remote control, and a head tracker were used to monitor and detect movement. the four different vr scenarios were as follows: • birthday celebration of a hedgehog • documentary on visual impairments • puzzle-based experience • basketball experience xiang et al., 2021 (62) vr participants received two types of vr-pat. the intervention was performed using an iphone and headphones. two types of vr-pat were as follows: • active vr-pat: the content of this intervention includes a game called virtual river cruise. the game involved guiding a boat to shore, with snow sculptures in the middle of the road where the participants could guide the boat by shaking their head and receiving the sculptures. • passive vr-pat: the content of this intervention is the same as the active intervention, but the participants do not interact in it. the pain was measured via the flacc pain assessment tool and the vas. ali et al., 2022 (63) vr participants received vr oculus with physical therapy seasons, each season lasting for 20 minutes. vr oculus uses a vr goggle to restrict children’s vision of the hospital environment. children can choose their favorite video from the beginning of the intervention. in addition to vr glasses, headphones are also provided to play audio. the pain was measured via the vas before and after the intervention. armstrong et al., 2022 (64) vr participants received vr-pat for 7 days during the dressing change. the vr-pat intervention includes a vr headset with a virtual river cruise game that runs on smartphones. the game involved guiding a boat to shore, with snow sculptures in the middle of the road where the participant could guide the boat by shaking its head and receiving the sculptures. the pain was measured via the appt. vr: virtual reality; vas: visual analog scale; grs: graph rating scale; vat: visual analog thermometer; augmented reality; flacc: faces, legs, activity, cry and consolability; fps-r: faces pain scale-revised; bsar: burns specific anxiety rating; bspas: burn specific pain anxiety scale; nprs: numeric pain rating scale; vns: verbal numeric scale; mhq: michigan hand outcomes questionnaire; nrs: numeric rating scale; vr-pat: virtual reality pain alleviation tool; appt: adolescent pediatric pain tool. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. norouzkhani et al. 22 table 3: sub-group analysis of included studies sub-categories number* effect size** 95%ci z p i2 bias good 19 -0.69 -1.03 to -0.35 3.97 <0.001 85.4% fair 6 -0.74 -1.06 to -0.43 4.59 <0.001 37.5% age group pediatric 14 -0.81 -1.22 to -0.39 3.83 <0.001 82.9% adult 7 -0.45 -1.01 to 0.10 1.59 0.11 84.0% both 4 -0.53 -0.81 to -0.26 3.0 0.003 77.7% design parallel 15 -0.59 -1.04 to -0.13 2.51 0.01 85.5% cross-over 10 -0.85 -1.13 to -0.57 5.96 <0.001 68.2% procedure dressing 12 -0.66 -1.20 to -0.11 2.37 0.02 87.1% physical therapy 8 -0.63 -0.95 to -0.31 3.84 <0.001 72.2% debridement 3 -0.91 -1.55 to -0.28 2.81 0.005 77.7% wound care 0 -0.35 -1.29 to 0.59 0.73 0.46 0 *: number of studies, **: standard mean difference. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations implications for health managers and policymakers implications for future research conclusion declarations references emergency. 2016; 4 (3): 155-158 brief report proper angle of sono-guided central venous line insertion hassan barzegari1, arash forouzan1, mohammad ali fahimi1∗, behzad zohrevandi2, mandana ghanavati1 1. department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. road trauma research center, guilan university of medical sciences, rasht, iran. received: november 2015; accepted: february 2016 abstract: introduction: determining the proper angle for inserting central venous catheter (cv line) is of great importance for decreasing the complications and increasing success rate. the present study was designed to determine the proper angle of needle insertion for internal jugular vein catheterization. methods: in the present case series study, candidate patients for catheterization of the right internal jugular vein under guidance of ultrasonography were studied. at the time of proper placing of the catheter, photograph was taken and auto cad 2014 software was used to measure the angles of the needle in the sagittal and axial planes, as well as patient’s head rotation. results: 114 patients with the mean age of 56.96 ± 14.71 years were evaluated (68.4% male). the most common indications of catheterization were hemodialysis (55.3%) and shock state (24.6%). the mean angles of needle insertion were 102.15 ± 6.80 for axial plane, 36.21 ± 3.12 for sagittal plane and the mean head rotation angle was 40.49 ± 5.09. conclusion: based on the results of the present study it seems that cv line insertion under the angles 102.15 ± 6.80 degrees in the axial plane, 36.21 ± 3.12 in the sagittal plane and 40.49 ± 5.09 head rotation yield satisfactory results. keywords: central venous catheters; vascular access devices; ultrasonography; emergencies; catheterization © copyright (2016) shahid beheshti university of medical sciences cite this article as: barzegari h, forouzan a, fahimi ma, zohrevandi b, ghanavati m. proper angle of sono-guided central venous line insertion. emergency. 2016; 4 (3): 155-158. 1. introduction insertion of central venous catheter (cv line) is a common procedure to reach the central veins with the aim of monitoring the patients regarding hemodynamic status, measuring central venous pressure (cvp), fluid therapy, infusion of vasoactive agents, etc. (1, 2). cv line insertion may be done either with the guidance of anatomic landmarks or ultrasonography. one of the problems caused by this procedure is the risk of pneumothorax and arterial puncture, which usually occur due to improper selection of angle and depth of needle insertion. the angle for needle insertion in both methods is suggested to be 30 45 degrees. yet, determining the angle, which minimizes the mentioned complications, is still needed (3-5). in a study, the proper needle tilt angle for internal jugular vein catheterization was shown to be 75 degrees ∗corresponding author: mohammad ali fahimi; department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, azadegan avenue, ahvaz, khuzestan province, iran. postal code: 6193673166 tel/fax: +986112229166 email:fahimi76@yahoo.com and higher (6). the present study aimed to determine the proper angle of needle insertion for right internal jugular vein catheterization. 2. methods 2.1. study design and settings the present case series study was designed to determine the proper angle of cv line insertion in internal jugular vein. patients admitted to imam khomeini and golestan hospitals, ahvaz, iran were included. based on the principles of helsinki declaration, researchers adhered to confidentiality of patient information and used the information only for research purposes. the study was approved by the ethical committee of ahvaz jondi shapour university of medical sciences, ahvaz, iran. written informed consent was obtained from all participants. 2.2. participants the participants were patients in need for catheterization of the right internal jugular vein, who were free of any evthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. barzegari et al. 156 ident deformity in chest and neck. unsuccessful insertion of catheter, change in hemodynamic status or occurrence of dysrhythmia during procedure, and not permitting frequent photography and venipuncture, were among the most important exclusion criteria. 2.3. procedure after screening the cases in need of cv line insertion based on common standards (not being able to reach a peripheral vein, cvp monitoring, need to vasopressor agent, and . . . ), patients underwent cardiopulmonary monitoring, pulseoximetry, and nasal oxygen therapy. then cv lines were inserted using the seldinger method, under sterilized conditions, under ultrasonography guidance, and local anesthesia with lidocaine 1%. all patients were in supine or trendelenburg position. sonography was done using a 7.5 mhz linear superficial probe under a sterilized nylon covering with a short axis approach on the right side of the neck in the anatomical position of internal jugular vein. catheter needle was aimed at the apex of a triangle made from the crossing of the medial one-third of the clavicle bone in the base and 2 sternal and clavicular heads of sternocleidomastoid muscle towards the right nipple. after blood aspiration and ensuring the needle has entered the jugular vein, the needle and patient’s head position were kept fixed and photographs were taken from two perpendicular views, patient’s right side (sagittal plane) and patient’s down side (axial plane) (figure 1). the camera was equipped with a protractor application and the camera lens was in horizontal state. taking a photo from the sagittal plane: while the patient was in supine position, the protractor was set to be parallel with the sagittal plane and when the needle entered the jugular vein and blood was aspirated, the center mark of the protractor was set at the place of needle insertion and the angle of needle with the horizontal line was measured. taking a photo from the axial plane: while the patient was in supine position, the protractor was set to be parallel with the axial plane on the thoracic area and the center mark of the protractor was set at the place of needle insertion. finally, when the needle entered the jugular vein and blood was aspirated, the angle of needle with horizontal line was measured. in addition, head rotation angle was measured in this plane by setting the zero point of the protractor on the mid sagittal line and measuring the angle of the line crossing the middle of the patient’s chin and the center mark of the protractor with vertical line. chest imaging was done to verify the place of the catheter and evaluate complications such as pneumothorax and hemothorax. all imaging and photography was performed by a trained emergency resident and 2 nurses. the angles were measured using auto cad 2014 software. demographic data of participants as well as duration of procedure and measured angles were collected via a predesigned checklist. in the end, data table 1: baseline characteristics of studied patients variables age (year) mean 56.96 ± 14.71 range 19 88 sex number (%) male 78 (68.4) female 36 (31.6) body mass index > 30 102 (89.5) < 30 12 (10.5) cause of catheterization shock 28 (24.6) post resuscitation 13 (11.4) hemodialysis 63 (55.3) inaccessible peripheral vein 8 (7) catheter change 1 (0.9) cvp measurement 1 (0.9) number of performers 1 103 (90.4) 2 11 (9.6) procedure time (minutes) mean 18.73 ± 1.51 range 15 23 cvp: central venous pressure. table 2: measured angles of head and needle in sagittal and axial planes angles mean ± sd (range) needle tilt (degree) in sagittal plane 36.21 ± 3.12 (28-45) in axial plane 102.15 ± 6.80 (90-115) head rotation (degree) in axial plane 40.49 ± 5.09 (29-52) sd: standard deviation. were presented as mean ± standard deviation and frequency and percentage using spss version 20. 3. results 120 patients were evaluated, 6 of which were excluded due to complications such as hematoma (4 cases) and carotid artery perforation (2 cases). the mean age of participants was 56.96 ± 14.71 years (68.4% male). the most common indications of catheterization were dialysis (55.3%) and shock state (24.4%). table 1 depicts the baseline characteristics of studied patients. table 2 shows the measured angles of head and needle in sagittal and axial planes. 4. discussion the findings of the present study showed that cv line insertion under the angles 102.15 ± 6.80 degrees in the axial plane, 36.21 ± 3.12 in the sagittal plane, and 40.49 ± 5.09 head rotation may yield good results. in recent years, the number this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 157 emergency. 2016; 4 (3): 157-158 figure 1: sample photographs taken. of patients in need of cv line insertion has increased due to various reasons (7). arterial puncture, hematoma, pneumothorax, hemothorax, nerve injury, arrhythmia, air embolism, cardiac tear, tamponade, and probability of infection after surgery, are among the most important complications of catheterization (8). catheterization, based on superficial landmarks is done in 1 attempt in about 20% of the time, while with the help of bedside ultrasonography, catheterization can be done with fewer complications and higher success rate (8). in a study aiming to determine the proper angle of needle insertion in the sagittal plane on the internal jugular vein, it was determined that a 16 degree insertion angle from the sagittal plane results in an increase in the probability of successful catheterization (9). in our study, mean sagittal angle of needle tilt from the horizontal line was about 36 degrees, which is vastly different from the mentioned study. in another study, the best angle for head rotation in internal jugular vein catheterization was reported to be ≥ 75 degrees (6). head rotation in the present study was found to be 40 degrees from vertical line. to date, few studies have been carried out for determining the accurate axial angle of the needle. considering the importance of this matter, it is suggested to design studies with proper sample size calculated based on existing data in the future. 5. conclusion based on the results of the present study it seems that cv line insertion under the angles 102.15 ± 6.80 degrees in the axial plane, 36.21 ± 3.12 in the sagittal plane and 40.49 ± 5.09 head rotation yield satisfactory results. 6. appendix 6.1. acknowledgements the authors wish to thank the staff of imam khomeini and golestan hospitals, ahvaz, iran, for their valuable assistance. 6.2. author contribution all authors pass the four criteria for authorship contribution based on the international committee of medical journal editors (icmje) recommendations. 6.3. conflict of interest none 6.4. funding/ support none references 1. o’grady np, alexander m, burns la, dellinger ep, garland j, heard so, et al. guidelines for the prevention of intravascular catheter-related infections. american journal of infection control. 2011;39(4):s1-s34. 2. troianos ca, hartman gs, glas ke, skubas nj, eberhardt rt, walker jd, et al. guidelines for performing ultrasound guided vascular cannulation: recommendations of the american society of echocardiography and the society of cardiovascular anesthesiologists. journal of the american society of echocardiography. 2011;24(12):1291-318. 3. warkentine fh, pierce mc, lorenz d, kim ik. the anatomic relationship of femoral vein to femoral artery in euvolemic pediatric patients by ultrasonography: implications for pediatric femoral central venous access. academic emergency medicine. 2008;15(5):426-30. 4. stone mb, moon c, sutijono d, blaivas m. needle tip visualization during ultrasound-guided vascular access: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. barzegari et al. 158 short-axis vs long-axis approach. the american journal of emergency medicine. 2010;28(3):343-7. 5. karakitsos d, labropoulos n, de groot e, patrianakos ap, kouraklis g, poularas j, et al. real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients. critical care. 2006;10(6):r162. 6. deangelis v, denny j, chyu d, jan t, lemaire a, chiricolo a, et al. the optimal angle of head rotation for internal jugular cannulation as determined by ultrasound evaluation. journal of cardiothoracic and vascular anesthesia. 2015. 7. ibrik o, samon r, roca r, viladoms j, mora j. tunneled catheters for hemodialysis of the type “twin tesio catheters system” by ultrasound-guided technique. retrospective analysis of 210 catheters. nefrologia. 2006;26(6). 8. roberts jr, hedges jr. clinical procedures in emergency medicine: elsevier health sciences; 2009. 9. ozbek s, apiliogullari s, erol c, kivrak as, kara i, uysal e, et al. optimal angle of needle entry for internal jugular vein catheterization with a neutral head position: a ct study. renal failure. 2013;35(4):492-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 83 emergency (2016); 4 (2): 83-87 original research correlation between central venous pressure and inferior vena cava sonographic diameter; determining the best anatomic location bahman naghipour1, gholamreza faridaalaee2* 1. department of anesthesiology, tabriz university of medical sciences, tabriz, iran. 2. emergency department, maragheh university of medical sciences, maragheh, iran. *corresponding author: gholamreza faridaalaee, emergency department, amiralmomenin hospital, amiralmomenin avenue, maragheh, iran. tel: 00989146677876 email: gholamrezafaridaalae@yahoo.com received: may 2015; accepted: june 2015 abstract introduction: the correlation of central venous pressure (cvp) with inferior vena cava (ivc) sonographic diameter has been reported in several studies. however, few studies have attempted to find the best anatomic location of measurement. therefore, the purpose of this study was determining the best anatomic location to find precise correlation between cvp and ivc diameter using transesophageal echocardiography (tee). methods: in the present diagnostic accuracy study, patients in need of central venous catheterization and tee were enrolled. maximum diameter of ivc were measured during expiratory phase of respiratory cycle at the level of diaphragm, 2cm above the diaphragm and at the point of entry into the right atrium using sonosite tee device. cvp was measured using an electronic transducer connected to the central venous line. the best location for sonography was determined via calculating and comparing area under the receiver operating characteristics (roc) curve (auc). results: 39 patients were enrolled (53.8% female). mean cvp was 6.8 ± 1.4 mmhg and 25 (64.1%) patients had normal cvp, while 14 (35.9%) showed elevated cvp (> 6 mmhg). evaluating auc showed that ivc diameter (p = 0.01), aorta diameter (p = 0.01) and ivc / aorta ratio (p = 0.004) had acceptable correlation with cvp. point of entry of ivc into the right atrium with auc of 0.98 (95% ci: 0.95 – 1.00) was the location of highest correlation with cvp. conclusion: based on the present findings, the ivc sonographic diameter and ivc / aorta ratio had acceptable correlation with cvp at the level of ivc entry into the right atrium. keywords: central venous pressure; vena cava, inferior; aorta, thoracic; echocardiography, transesophageal cite this article as: naghipour b, faridaalaee g. correlation between central venous pressure and inferior vena cava sonographic diameter; determining the best anatomic location. emergency. 2016; 4(2):83-87. introduction: ehydration is the main cause of morbidity and mortality in critically ill patients and assessment of intravascular volume status (ivs) is essential for their management (1, 2). however, diagnosis of dehydration and intravascular volume loss is sometimes difficult (3). some clinical signs and symptoms are assessed for determining ivs but they have low sensitivity and specificity (4). it could be determined by measuring peripheral blood pressure, but in many conditions, it does not reflect accurate intravascular volume status. hypotension is detected in late stage of shock, especially when compensatory mechanisms fail (5). central venous pressure (cvp) is one of the indices of ivs and early goals of goal-directed therapy approach (6, 7). a common and conventional procedure for measuring cvp is inserting a catheter in a central vein such as internal jugular, subclavian, and femoral veins. however, the major problem with this procedure is the probability of some dangerous and sometimes lethal complications such as arterial puncture, pneumothorax, hemothorax, misplacement in carotid artery, infection, and other rare complications such as cardiac tamponade etc. in addition, central venous catheter insertion is a time consuming and invasive procedure (8-12). recently, researchers and physicians have attempted to measure cvp with non-invasive procedures such as ultrasonography, transthoracic echocardiography, and transesophageal echocardiography (tee). they have reported a correlation between sonographic inferior vena cava (ivc) diameter and cvp (1, 9, 13-16). donahue et al. found a direct correlation between internal jugular vein sonographic diameter and cvp (17). however, few studies have attempted to find d this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com naghipour et al 84 the best anatomic location and cut points. therefore, the purpose of this study was determining the best anatomic location to find precise correlation between cvp and ivc diameter using tee. methods: study design and setting in the present prospective cross-sectional study, the correlation of sonographic ivc diameter, aorta diameter, and ivc / aorta ratio with cvp were evaluated. patients in need of catheterization and tee who were referred to a teaching hospital in tabriz, iran, from 2013 to 2015 were enrolled. this study was approved by the ethics committee of tabriz university of medical sciences. the patients or their relatives had signed the informed written consent form before initiation of the study and the researchers adhered to the principles of helsinki declaration. participants: over the course of the study, all patients over 18 years old who needed central venous catheterization and tee were included. consecutive sampling was used and the patients’ need for catheterization and tee was determined by an independent cardiologist. those who were prohibited from assuming a supine position (severe orthopnea, intracerebral pressure rising), patients who had moderate-to-severe tricuspid regurgitation, congestive heart failure, broncho-pulmonary dysplasia, body mass index > 30, and renal and liver diseases were excluded. measurements: central venous catheterization and tee were done in the operating room. after central catheterization using seldinger technique, cvp was measured using electronic transducer connected to the cv line inserted in the right internal jugular vein by central approach while the patient was placed in a 15-degree trendelenburg position (18). ivc and aorta diameter were measured using tee (sonos 5500; philips medical systems, andover, ma) and a 3.5 mhz probe. all the ultrasonographies were done by a trained cardiology fellow who was blind to the patients’ cvp. ivc and aorta diameter were measured at end-expiration and end-diastole in 2-dimensional longaxis mid-esophageal bicaval view. measurements were done in the level of diaphragm, 2 centimeters above the diaphragm and at the point of entry into the right atrium and recorded in millimeter. all evaluations were done in the supine position. statistical analysis sample size was determined to be about 45 patients considering minimum correlation coefficient of ivc diameter and cvp to be 0.48 with 95% confidence interval (ci) (α = 0.05) and 90% power (β = 0.1). analyzes were done with spss 20. spearman’s rank correlation test was used to determine the relationship between sonographic ivc diameter and cvp. best index (ivc diameter, aorta diameter, or ivc / aorta ratio) and best measurement location (the level of diaphragm, 2cm above the diaphragm and at the point of entry into the right atrium) were determined via calculating and comparing area under the receiver operating characteristics (roc) curve (auc). normal cvp was considered 2-6 mmhg for this purpose (19). in all analyses, p < 0.05 was considered as significance level. table 1: baseline characteristics of the patients variable mean (sd) median minimum maximum age (year) 62.1 (5.8) 61 54 83 weight (kg) 69.5 (11.0) 68 53 94 height (cm) 161.3 (7.3) 160 145 178 sbp (mmhg) 110 (9.6) 110 95 130 dbp (mmhg) 63.8 (6.9) 63 45 80 hr (beat/min) 71.3 (12.4) 73 45 90 cvp (mmhg) 6.8 (1.04) 7 4 9 ivc diameter (mm) point of entry into the right atrium 23.2 (3.6) 22 18 31 2cm above the diaphragm 18.6 (2.6) 19 12 23 level of diaphragm 17.1 (3.4) 17 10 25 aorta diameter (mm) point of entry into the right atrium 24.6 (2.1) 25 21 29 2cm above the diaphragm 22.4 (1.6) 23 19 27 level of diaphragm 21.3 (1.6) 21 19 27 ivc/aorta ratio point of entry into the right atrium 0.94 (0.09) 0.96 0.78 1.12 2cm above the diaphragm 0.83 (0.13) 0.86 0.52 1.05 level of diaphragm 0.81 (0.16) 0.81 0.48 1.09 sbp: systolic blood pressure, dbp: diastolic blood pressure, hr: heart rate, cvp: central venous pressure, ivc: inferior vena cava. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 85 emergency (2016); 4(2): 83-87 results: over the course of the study, 39 patients were included (53.8% male; mean age 62.1 ± 5.8 years). baseline characteristics of the patients are summarized in table 1. mean cvp was 6.8 ± 1.4 mmhg and 25 (64.1%) patients had normal cvp, while 14 (35.9%) showed elevated cvp (> 6 mmhg). the relationship of cvp with ivc and aorta diameter table 2 shows the relationship of cvp with sonographic ivc diameter, aorta diameter, and ivc / aorta. as can be seen, cvp had a significant correlation with ivc diameter at the point of entry into the right atrium (r = 0.85; p < 0.001), 2cm above the diaphragm (r = 0.48; p = 0.002), and in the level of diaphragm (r = 0.85; p < 0.001). at the same time, aorta diameter showed a significant correlation with cvp at the point of entry into the right atrium (r = 0.68; p < 0.001) and 2cm above the diaphragm (r = 0.44; p = 0.005). ivc / aorta ratio also had a significant correlation with cvp at all 3 points. comparing diagnostic values of ivc and aorta diameter evaluation of area under the roc curve showed that the best point for determining cvp was at the point of entry into the right atrium for ivc diameter (p = 0.01), aorta diameter (p = 0.01), and ivc / aorta ratio (p = 0.004) (figure 1a-c). therefore, to identify the best index among the 3, their area under the roc curve was compared at this point (table 3 and figure 1-d). based on the findings, ivc diameter (auc = 0.98; 95% ci: 0.95-1.0) and ivc / aorta ratio (auc = 0.96; 95% ci: 0.92-1.0) had higher diagnostic values compared to aorta diameter (auc = 0.89; 95% ci: 0.79-0.98) at this point (p = 0.01). discussion: this study was conducted to find the precise anatomic location with the best correlation between cvp and ivc diameter, aorta diameter, or ivc/aorta ratio. based on the present findings, the ivc diameters and ivc / aorta ratio had acceptable correlation with cvp. in addition, the point of ivc entry into the right atrium was the best anatomic location to estimate cvp. ultrasound is a noninvasive, easy, available, and useful tool for assessment of volume status (20). wiwatworapan et al. showed that when end-expiratory ivc diameter was lower than 10 mm, the cvp would be 10 cmh2o, (sensitivity 77% and specificity 91%) and when end-expiratory ivc diameter was 15 mm, cvp would be 15 cmh2o (sensitivity 90% table 2: correlation of cvp with ivc and aorta diameters, and ivc/aorta ratio index r 95 % ci p ivc point of entry into the right atrium 0.85 0.73-0.92 <0.001 2cm above the diaphragm 0.48 0.19-0.69 0.002 level of diaphragm 0.68 0.47-0.82 <0.001 aorta point of ivc entry into the right atrium 0.68 0.45-0.81 <0.001 2cm above the diaphragm 0.44 0.15-0.66 0.005 level of diaphragm 0.15 -0.17-0.44 0.37 ivc/aorta ratio point of ivc entry into the right atrium 0.69 0.48-0.83 0.001 2cm above the diaphragm 0.43 0.16-0.68 0.007 level of diaphragm 0.53 0.26-0.72 0.001 ivc: inferior vena cava; ci: confidence interval. table 3: area under roc curve of ivc and aorta diameters, and ivc/aorta ratio in estimation of cvp index auc 95 % ci p ivc point of entry into the right atrium 0.98 0.95-1.0 0.01 2cm above the diaphragm 0.78 0.62-0.93 level of diaphragm 0.81 0.66-0.96 aorta point of ivc entry into the right atrium 0.89 0.79-0.98 0.01 2cm above the diaphragm 0.64 0.45-0.84 level of diaphragm 0.53 0.45-0.84 ivc/aorta ratio point of ivc entry into the right atrium 0.96 0.92-1.0 0.004 2cm above the diaphragm 0.67 0.48-0.85 level of diaphragm 0.80 0.66-0.94 ivc: inferior vena cava; auc: area under curve; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com naghipour et al 86 and specificity 89%) (21). baumann et al. measured cvp using ultrasound and concluded that although estimation of cvp by ultrasound is easy, but absolute values differ from invasive measurements of cvp and ivc indices alone can’t be used to accurately estimate intravascular volume status (22). in line with our study, arthur et al. reported a statistically significant correlation between ivc diameter and cvp (16). in addition, de lorenzo et al. compared different anatomic locations such as subxiphoid, mid-abdomen and suprailiac to find best anatomic location for calculating the correlation between cvp and ivc diameter. they reported that suprailiac view had better correlation with cvp compared to other anatomic locations but measurement of cvp using ultrasound had low yield (23). yet, some studies demonstrate that an increase or decrease in the collapsibility of ivc can be helpful in management of patients in poor condition. based on the findings of those studies, the combination of absolute ivc diameter and collapsibility level, which is known as caval index, is a better estimation of cvp compared to absolute ivc diameter and can be a good replacement for invasive tests (24-26). the mechanism of this method is based on the fact that the negative pressure generated while inhalation leads to an increase in venous return to heart and ivc collapse. while exhaling, venous return decreases and ivc diameter goes back to the basic state (25, 27, 28). in the present study, caval index could not be assessed, as the ultrasonography film could not be recorded in the device used. therefore, it is recommended to take this into account in future studies. another limitation of this study was the little sample size, yet the minimum power calculated for this study was 85%; so it seems that little sample size has not affected the results of this study. conclusion: based on the present findings, the ivc sonographic diameter and ivc / aorta ratio had acceptable correlation with cvp at the level of ivc entry into the right atrium. acknowledgments: authors would like to thank all the staff of operating a b c d figure 1: comparison of area under the curve of inferior vena cava (ivc) diameter (a), aorta diameter (b), and ivc / aorta ratio (c) in different points in estimation of central venous pressure and comparison between the three indices (d). p = 0.01 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1-specificity auc of ivc at right atrium= 0.98 auc of ivc at 2 cm above diaphragm= 0.78 auc of ivc diaphragm level=0.81 p = 0.01 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1-specificity auc of aorta at right atrium = 0.89 auc of aorta at 2 cm above diaphragm= 0.64 auc of aorta at diaphragm level=0.53 p=0.004 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1-specificity auc ivc/aorta at right atrium= 0.96 auc of ivc/aorta at 2 cm above diaphragm= 0.67 auc of ivc/aorta at diaphragm level= 0.80 p = 0.01 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1-specificity auc of ivc= 0.983 auc of aorta= 0.89 auc of ivc/aorta= 0.96 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 87 emergency (2016); 4(2): 83-87 room in shahid madani hospital. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. thanakitcharu p, charoenwut m, siriwiwatanakul n. inferior vena cava diameter and collapsibility index: a practical noninvasive evaluation of intravascular fluid volume in criticallyill patients. j med assoc thai. 2013;96:s14-22. 2. control cfd, prevention. managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. pediatrics. 2004;114(2):507. 3. riccardi a, chiarbonello b, minuto p, guiddo g, corti l, lerza r. identification of the hydration state in emergency patients: correlation between caval index and bun/creatinine ratio. eur rev med pharmacol sci. 2013;17(13):1800-3. 4. gorelick mh, shaw kn, murphy ko. validity and reliability of clinical signs in the diagnosis of dehydration in children. pediatrics. 1997;99(5):e6. 5. pershad j, myers s, plouman c, et al. bedside limited echocardiography by the emergency physician is accurate during evaluation of the critically ill patient. pediatrics. 2004;114(6):e667-71. 6. marcelino p, fernandes a, marum s, ribeiro j. non-invasive evaluation of central venous pressure by echocardiography. rev port cardiol. 2002;21(2):125-33. 7. rivers e, nguyen b, havstad s, et al. early goal-directed therapy in the treatment of severe sepsis and septic shock. n engl j med. 2001;345(19):1368-77. 8. gong p, huang x-e, chen c-y, liu j-h, meng a-f, feng j-f. comparison of complications of peripherally inserted central catheters with ultrasound guidance or conventional methods in cancer patients. asian pac j cancer prev. 2012;13(5):18735. 9. jardim jm, lacerda ra, soares ndjd, nunes bk. evaluation of practices for the prevention and control of bloodstream infections in a government hospital. rev esc enferm usp. 2013;47(1):38-45. 10. kaye c, smith d. complications of central venous cannulation. bmj. 1988;297(6648):572-3. 11. mcgee dc, gould mk. preventing complications of central venous catheterization. n engl j med. 2003;348(12):1123-33. 12. pivalizza eg, gumbert sd, marasigan b, guzman-reyes s. 'evidence'for practice guidelines for central venous access? anesthesiology. 2012;117(4):916-7. 13. chen l, kim y, santucci ka. use of ultrasound measurement of the inferior vena cava diameter as an objective tool in the assessment of children with clinical dehydration. acad emerg med. 2007;14(10):841-5. 14. chen l, hsiao a, langhan m, riera a, santucci ka. use of bedside ultrasound to assess degree of dehydration in children with gastroenteritis. acad emerg med. 2010;17(10):1042-7. 15. bailey jk, mccall j, smith s, kagan rj. correlation of internal jugular vein/common carotid artery ratio to central venous pressure: a pilot study in pediatric burn patients. j burn care res. 2012;33(1):89-92. 16. arthur me, landolfo c, wade m, castresana mr. inferior vena cava diameter (ivcd) measured with transesophageal echocardiography (tee) can be used to derive the central venous pressure (cvp) in anesthetized mechanically ventilated patients. echocardiography. 2009;26(2):140-9. 17. donahue sp, wood jp, patel bm, quinn jv. correlation of sonographic measurements of the internal jugular vein with central venous pressure. am j emerg med. 2009;27(7):851-5. 18. ely ew, smith ac, chiles c, et al. radiologic determination of intravascular volume status using portable, digital chest radiography: a prospective investigation in 100 patients. crit care med. 2001;29(8):1502-12. 19. jeremias a, brown d. cardiac intensive care. 2 ed. philadelphia: elsevier health sciences; 2010. p. 384. 20. zengin s, al b, genc s, et al. role of inferior vena cava and right ventricular diameter in assessment of volume status: a comparative study: ultrasound and hypovolemia. am j emerg med. 2013;31(5):763-7. 21. wiwatworapan w, ratanajaratroj n, sookananchai b. correlation between inferior vena cava diameter and central venous pressure in critically ill patients. j med assoc thai. 2012;95(3):320-4. 22. baumann ua, marquis c, stoupis c, willenberg ta, takala j, jakob sm. estimation of central venous pressure by ultrasound. resuscitation. 2005;64(2):193-9. 23. de lorenzo ra, morris mj, williams jb, et al. does a simple bedside sonographic measurement of the inferior vena cava correlate to central venous pressure? j emerg med. 2012;42(4):429-36. 24. goldflam k, saul t, lewiss r. focus on: inferior vena cava ultrasound. acep news. 2011;6:24-5. 25. nagdev ad, merchant rc, tirado-gonzalez a, sisson ca, murphy mc. emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure. ann emerg med. 2010;55(3):290-5. 26. sridhar h, mangalore p, chandrasekaran v, manikam r. caval aorta index and central venous pressure correlation in assessing fluid status!“ultrasound bridging the gap”. isrn emerg med. 2012;2012:1-5. 27. tayal v, blaivas m. american college of emergency physicians: acep emergency ultrasound guidelines-2001. ann emerg med. 2009;53:470-81. 28. blehar dj, dickman e, gaspari r. identification of congestive heart failure via respiratory variation of inferior vena cava diameter. am j emerg med. 2009;27(1):71-5. archives of academic emergency medicine. 2019; 7 (1): e12 ca s e re p o rt conservative management of asymptomatic pneumoperitoneum; report of two cases leila alizadeh1, mahdieh shakeri-darzekonani1, amin sadrazar1, masoud nouri-vaskeh2,3∗, sedigheh basirjafari4 1. liver and gastrointestinal diseases research center, tabriz university of medical sciences, tabriz, iran. 2. connective tissue diseases research center, tabriz university of medical sciences, tabriz, iran. 3. medical philosophy and history research center, tabriz university of medical sciences, tabriz, iran. 4. department of radiology, tabriz university of medical sciences, tabriz, iran. received: november 2018; accepted: december 2018; published online: 3 january 2019 abstract: peptic ulcer disease is a common gastrointestinal disorder, the prevalence of which has reduced in recent years due to effective new treatments. peptic ulcer perforation is an emergent life-threatening condition that causes pneumoperitoneum and septic shock. it often requires surgical procedures. we describe two cases of peptic ulcer perforation with only mild discomfort on the epigastric region since several months before. the patients were treated with a high dose proton pump inhibitor and conservative treatment without surgical procedures. weekly follow up of the cases showed that the clinical condition of patients remained stable without any new signs and symptoms. this report shows that noninvasive treatment alone can be effective in some cases with mild symptoms. keywords: peptic ulcer perforation; pneumoperitoneum; proton pump inhibitors; conservative treatment cite this article as: alizadeh l, shakeri-darzekonani m, sadrazar a, nouri-vaskeh m, basirjafari s. conservative management of asymptomatic pneumoperitoneum; report of two cases. arch acad emerg med. 2019; 7 (1): e12. 1. introduction peptic ulcer diseases (pud) is one of the common gastroduodenal disorders that affects about 4 million people per year (1). gastrointestinal (gi) perforation is a life-threatening complication of pud (2). it causes about 5% of abdominal emergencies with up to 30% mortality and up to 50% morbidity rates (3, 4). due to h. pylori eradication by effective antibiotic therapy and widespread use of protein pump inhibitors (ppis), the prevalence of pud has decreased. however, the life-threatening complications of pud have not decreased (5). peptic ulcer perforation presents as an acute abdomen with peritonitis, which can lead to septic shock and death. radiological examination has a basic role in diagnosis of gastric ulcer perforation (6). medical therapy, endoscopic and other non-surgical managements have decreased the role of surgery; nevertheless, the prevalence ∗corresponding author: masoud nouri-vaskeh, connective tissue diseases research center, tabriz university of medical sciences, tabriz, iran. postal code: 5166614756 email: mnvaskeh@tbzmed.ac.ir tel: (+98) 4133259778 fax: (+98) 4133345591 of peptic ulcer perforation is in a stable range and surgery has an important role in its treatment (7). however, due to the risk of complications after peptic ulcer perforation surgeries, sometimes other modalities other than open surgery should be considered (8). in the present paper, we report two asymptomatic pneumoperitoneum cases due to perforated peptic ulcer, which were treated with high dose ppi and conservative treatment without surgical procedures. 2. case presentation: 2.1. case 1 a 34-year-old man with a 2-year history of peptic ulcer was admitted to the gastrointestinal (gi) ward in a tertiary referral hospital. the patient’s chief complaints were one episode of hematemesis 4 days ago and persistent mild abdominal pain in the epigastric region. the patient was addicted to 2.5 mg methadone per day. vital signs were in normal ranges. physical examination was normal and did not demonstrate any tenderness and guarding in the abdomen. upper gi endoscopy was performed after 12 hours of fasting. a clean base this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. alizadeh et al. 2 gastric ulcer in the gastric outlet with gastric outlet obstruction pattern and grade a esophagitis were seen in the upper gi endoscopy. the baseline laboratory analysis revealed the following: white blood cell (wbc) count: 6100/µl (segment: 60.4%), hemoglobin: 15.6g/dl; platelet count: 176000/µl; ldh: 260 iu/ml and, other lab tests including liver tests, creatinine, and blood urea nitrogen, were within the normal range. serial laboratory test measurements did not show any out of range changes. non-contrast abdominal computed tomography (ct) revealed pneumoperitoneum around the stomach and liver (figure 1). ct scan with contrast revealed hydro pneumoperitoneum at porta hepatis and aortocaval regions. the consultant surgeon recommended follow up by endoscopy and antibiotic therapy. the patient was treated with high dose pantoprazole, hydration and bowel rest and intravenous ceftriaxone and, metronidazole. during hospitalization, abdominal pain resolved and no abdominal tenderness and guarding developed. finally, he was discharged in good health with high dose oral pantoprazole, metronidazole and cefixime, and was also advised to refer to the gi clinic after a week. four-month weekly follow up showed no abdominal symptoms and normal quality of life. 2.2. case 2 a 52-year-old man with a history of dyspepsia from 6-8 months before with chief complaint of three hematemesis episodes 3 days before was admitted to the gi ward. he had no history of melena, hematochezia, dyspnea, fatigue, syncope and orthostatic dizziness. he had no history of pud and had not reported taking non-steroidal anti-inflammatory drugs (nsaids), ppis or histamine receptor antagonists. he was not an alcoholic or smoker. he was addicted to opiates. the patient’s familial history was negative. physical examination on admission revealed stable vital signs and normal abdominal examination. rectal examination was normal and no visible hemorrhoid was observed. his endoscopy showed scar and ulcer in the duodenal bulb and, duodenal bulb deformity due to a chronic ulcer. abdominal ct scan revealed a pneumoperitoneum (figure 2). consultant surgeon recommended follow up. the baseline laboratory analysis during admission revealed the following: wbc count: 7200/µl (segment: 63.8%); hemoglobin: 13.0g/dl; platelet count: 228000/µl; creatinine: 1.03mg/dl; esr: 9 mm/hr; crp: 40 mg/l. liver function tests and coagulation panel were within normal limits. during hospitalization, there were no out of rage changes in laboratory findings. he was treated with intravenous ceftriaxone and, metronidazole and also high dose pantoprazole. after 10 days, the patient was discharged from the hospital with oral pantoprazole, metronidazole and cefixime. five-month weekly follow up showed that during that time there were only a few problems due to the dyspepsia he already had. figure 1: pneumoperitoneum in pararenal space and right perihepatic space. figure 2: oral and intravenous contrast abdominal computed tomography scan. the leak of the contrast material from gastrointestinal tract and its extension to the left pararenal space was seen. ascites and pneumoperitoneum were seen in subhepatic space. 3. discussion perforated peptic ulcer is a condition, which causes the leakage of gas and gastroduodenal content into the peritoneal cavity. peptic ulcer perforation mostly affects the anterior wall of the duodenum, and the antral and lesser curvature of stomach (9). an accurate history, physical examination, and ct scan as a more sensitive method are required for diagnosis of pneumoperitoneum (10). the patient’s history and endoscopy observations along with imaging findings most probably help distinguish the free air in the abdomen cavity due to peptic ulcer perforation. when there is no sign of peritonitis and the patient’s general condition is well, conservative treatment should be considered (11, 12). multidetector ct scan is more helpful for detecting the origin of gi tract perforation (13). proximal gi perforation is probable when free air is present just around the liver, stomach, duodenum and not in the pelvis (14). in these cases abdominal ct scan should be performed. in case 1, on ct scan, incidentally, pneumoperitoneum was found around the stomach, which was probably related to gastric perforation. in case 2, ct scan showed pneumoperitoneum around the duodenum, which was likely related to duodenal perforation. patients with pneumoperitoneum in the upper abdomen (such as the two cases in this report), who have mild symptoms, stable hemodynamics and no signs of acute abdomen might have micro perforation in their stomach (like case 1) and duodenum (like case 2), in which case they should initiate conservative therapy with anti-ulcer agents such as ppi, h2 blocker, and intravenously administered antibiotics. the pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e12 tient should be followed carefully (15). the follow up of these two cases showed that their condition remained stable. in conclusion, we reported two pneumoperitoneum cases due to peptic ulcer perforation with mild symptoms and stable conditions, which were managed without the need for surgical procedures. more similar cases and further evaluations are needed for better comprehension of the outcome of conservative treatment in asymptomatic peptic ulcer perforations. 4. appendix 4.1. acknowledgements the authors would like to express their special thanks to the endoscopy ward staff. 4.2. authors contribution la, as managed the patients. ms and mn followed the patients. sb reported images. mv and ms wrote the draft. all authors revised and approved the final version of the manuscript. authors’ orcids leila alizadeh: 0000-0001-9764-7713 mahdieh shakeri-darzekonani: 0000-0002-4015-4392 amin sadrazar: 0000-0003-3703-1508 masoud nouri-vaskeh: 0000-0002-6656-0292 sedigheh basirjafari: 0000-0003-4980-2648 4.3. conflict of interest none declared. 4.4. funding no funding was received for this study. references 1. zelickson ms, bronder cm, johnson bl, et al. helicobacter pylori is not the predominant etiology for peptic ulcers requiring operation. the american surgeon. 2011;77(8):1054-60. 2. avila alvarez aa, parra jf, buitrago da, rodriguez f, moreno a. gastric perforation and phlegmon formation by foreign bodyingestion. emerg (tehran). 2014;2(3):141-3. 3. suriya c, kasatpibal n, kunaviktikul w, kayee t. diagnostic indicators for peptic ulcer perforation at a tertiary care hospital in thailand. clin exp gastroenterol. 2011;4:2839. 4. soreide k, thorsen k, harrison em, et al. perforated peptic ulcer. lancet. 2015;386(10000):1288-98. 5. lanas a, carrera-lasfuentes p, garcia-rodriguez la, et al. outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with highor low-risk stigmata. scand j gastroenterol. 2014;49(10):1181-90. 6. baghdanian ah, baghdanian aa, puppala s, tana m, ohliger ma. imaging manifestations of peptic ulcer disease on computed tomography. semin ultrasound ct mr. 2018;39(2):183-92. 7. eisner f, hermann d, bajaeifer k, glatzle j, konigsrainer a, kuper ma. gastric ulcer complications after the introduction of proton pump inhibitors into clinical routine: 20-year experience. visc med. 2017;33(3):221-6. 8. smith rs, sundaramurthy sr, croagh d. laparoscopic versus open repair of perforated peptic ulcer: a retrospective cohort study. asian j endosc surg. 2018. 9. ramakrishnan k, salinas rc. peptic ulcer disease. am fam physician. 2007;76(7):1005-12. 10. hainaux b, agneessens e, bertinotti r, et al. accuracy of mdct in predicting site of gastrointestinal tract perforation. ajr am j roentgenol. 2006;187(5):1179-83. 11. tanaka r, kameyama h, nagahashi m, et al. conservative treatment of idiopathic spontaneous pneumoperitoneum in a bedridden patient: a case report. surg case rep. 2015;1(1):69. 12. shibukawa n, ouchi s, wakamatsu s, wakahara y, tatsumi n, kaneko a. a rare case of gastric ulcer penetrating the pancreas that was successfully managed by conservative therapy. intern med. 2017;56(17):2277-9. 13. sheikh mt, sheikh mt, jan m, khan ha, vashisht gp, wani ml. role of multi-detector ct (mdct) in evaluation of bowel diseases. j clin diagn res. 2017;11(7):tc11tc3. 14. oguro s, funabiki t, hosoda k, et al. 64-slice multidetector computed tomography evaluation of gastrointestinal tract perforation site: detectability of direct findings in upper and lower gi tract. eur radiol. 2010;20(6):1396403. 15. mularski ra, sippel jm, osborne ml. pneumoperitoneum: a review of nonsurgical causes. crit care med. 2000;28(7):2638-44. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation: discussion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 136 emergency (2016); 4 (3): 136-139 original research outcome of blunt abdominal traumas with stable hemodynamic and positive fast findings firooz behboodi1, zahra mohtasham-amiri2, navid masjedi1*, reza shojaie1, peyman sadri3 1. department of general surgery, guilan university of medical sciences, rasht, ir iran. 2. department of preventive & social medicine, guilan university of medical science, rasht, ir iran. 3. department of general surgery, zanjan university of medical science, zanjan, ir iran. *corresponding author: navid masjedi. department of general surgery, guilan university of medical science, tehran road km6, rasht, guilan; iran; e-mail: navid.masjedi1983@gmail.com; tel: 00981333690884; fax: 00981333690036 received: june 2015; accepted: september 2015 abstract introduction: focused assessment with sonography for trauma (fast) is a highly effective first screening tool for initial classification of abdominal trauma patients. the present study was designed to evaluate the outcome of patients with blunt abdominal trauma and positive fast findings. methods: the present prospective cross-sectional study was done on patients over 7 years old with normal abdominal examination, positive fast findings, and available abdominopelvic computed tomography (ct) scan findings. the frequency of need for laparotomy as well as its probable risk factors were calculated. results: 180 patients were enrolled (mean age: 28.0 ± 11.5 years; 76.7% male). fast findings were confirmed by abdominopelvic ct scan in only 124 (68.9%) cases. finally, 12 (6.6%) patients needed laparotomy. mean age of those in need of laparotomy was significantly higher than others (36.75 ± 11.37 versus 27.34 ± 11.37, p = 0.006). higher grading of spleen (p = 0.001) and hepatic (p = 0.038) ruptures increased the probability of need for laparotomy. conclusion: 68.9% of the positive fast findings in patients with blunt abdominal trauma and stable hemodynamics was confirmed by abdominopelvic ct scan and only 6.6% needed laparotomy. simultaneous presence of free fluid and air in the abdominal area, old age, and higher grading o solid organ injuries were factors that had a significant correlation with need for laparotomy. keywords: abdominal injuries; wounds, nonpenetrating; patient outcome assessment; ultrasonography; tomography, x-ray computed cite this article as: behboodi f, mohtasham-amiri z, masjedi n, shojaie r, sadri p. outcome of blunt abdominal traumas with stable hemodynamic and positive fast findings. emergency. 2016; 4(3):136-139. introduction: raumatic injuries are the major cause of mortality in the under 40 year old population and abdominal trauma is the third common trauma with a high rate of morbidity and mortality (1-3). rapid diagnosis and treatment can decrease the rate of abdominal trauma related mortality, up to 50% (4). immediate referral of the victim to a trauma center and timely diagnosis and treatment play a key role in improvement of patient outcome. when a patient with suspected blunt abdominal trauma is presented to emergency department (ed), the physicians look to determine the presence of intra-abdominal injuries and predict patient outcome (5). focused assessment with sonography for trauma (fast) is a highly effective first screening tool for initial classification of abdominal trauma patients (6). yet, like all sonography techniques, its diagnostic value depends on the operator’s skill. therefore, the findings of the studies are sometimes contradictory (7-9). the results of most existing studies show that fast has average sensitivity and high specificity in detection of abdominal traumatic injuries (8, 10, 11). the effect of using this diagnostic test on improvement of patient management is still a matter of debate. the present study was designed to evaluate the outcome of patients with blunt abdominal trauma and positive fast findings. methods: the present prospective cross-sectional study was done with the aim of evaluating the outcome of patients with blunt abdominal trauma and positive fast results. 180 patients presented to the ed of poursina hospital, rasht, iran, during 2013 and 2014 were enrolled using convenience sampling. the protocol of the present study was approved by the ethics committee of guilan university of medical sciences. all the researchers adhered to the t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 137 emergency (2016); 4 (3): 136-139 principles of helsinki declaration. inclusion criteria consisted of age over 7 years, normal abdominal examination and positive fast findings. hemodynamic unstability, abnormal abdominal examination, pregnancy, lost to follow-up were among the exclusion criteria. the patients underwent abdominal sonography by a trained (for 8 hours) senior emergency medicine resident and in case of positive fast findings, abdominopelvic computed tomography (ct) scan with intravenous (iv) contrast was performed. demographic data (age, sex) as well as sonography and ct scan findings, and need for laparotomy were recorded. need for laparotomy was considered the final outcome of the present study. fast was carried out using a sonoscape ssi-5500bw ultrasonography machine with a 3.5 – 5 mhz probe. ct scan was done using a toshiba asteion 16 slice scanner and interpreted by a radiologist blind to fast and clinical findings. positive fast was defined as presence of solid organ injury or free abdominal fluid in at least one of the morison's, spleno-renal or retro-vesical pouches. the sample size was calculated to be 170 cases, considering the 20% prevalence of need for laparotomy in positive fast cases (12), α = 0.05, and d = 0.06. data were analyzed using stata 11.0. quantitative data were reported as mean and standard deviation (sd) and qualitative ones as frequency and percentage. independent ttest was used to compare the average age and hemoglobin level of operated and non-operated patients. in addition, chi square or fisher’s exact tests were used to compare frequency. in all analyses p < 0.05 was considered as significance level. results: 180 patients with blunt abdominal trauma, stable hemodynamic and positive fast findings were enrolled (mean age: 28.0 ± 11.5 years; 76.7% male). table 1 shows age and sex distribution of the participants. fast findings were confirmed by abdominopelvic ct scan in only 124 (68.9%) cases (figure 1). hepatic (26.7%) and spleen (7.8%) ruptures, and presence of free fluid (12.8%) were the most common ct findings. finally, 12 (6.6%) patients needed laparotomy, 7 (58.33%) of which had free abdominal fluid and air, 1 (8.33%) had ruptured liver, and 4 (33.34%) had ruptured spleen. mean age of those in need of laparotomy was significantly higher than others (36.75 ± 11.37 versus 27.34 ± 11.37, p = 0.006). higher grading of spleen (p = 0.001) and hepatic (p = 0.038) ruptures increased the probability of need for laparotomy (table 2). discussion: based on the results of the present study, only 68.9% of the positive fast findings in patients with blunt abdominal trauma and stable hemodynamics was confirmed by abdominopelvic ct scan. finally, only 6.6% of these patients needed laparotomy. simultaneous presence of free fluid and air in the abdominal area, old age, and higher grading of solid intra-abdominal organ injuries were factors that had a significant correlation with need for laparotomy. cunningham et al. express that all patients with evidence of free abdominal fluid in ct scan need laparotomy (13). in a study by yanar et al. only 33% of the patients needed laparotomy. they believe that non-operative treatment will be efficient in 75% of cases. this study showed that solid viscus score, more than 20% decrease in hematocrit, and level of serum lactate on admission are the most important predictive factors of non-operative management failure (14). the present study showed that simultaneous presence of free abdominal fluid and air is directly related to need for laparotomy. in addition, 93.3% of non-operative treatments were successful. this high rate might be due to the high percentage of solid organ injury cases, as a high percentage of solid organ injury table 1: age and sex distribution of the patients variable frequency (%) sex male 138 (76.7) female 42 (23.3) age (years) < 10 13 (7.2) 11-20 42 (23.3) 21-30 49 (27.2) 31-40 54 (30.0) 41-50 15 (8.3) 51-60 7 (3.9) figure 1: abdominopelvic computed tomography scan findings of fast positive patients. 31.11 26.66 13.89 12.78 7.78 3.89 3.89 0 20 40 normal hepatic rupture ruptured spleen free fluid kidney rupture free fluid and free air multi-organ damage percentage of patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com behboodi et al 138 patients, even those with higher grading, are successfully treated with non-operative treatments (15). the existing studies show that fast has low sensitivity and high specificity in identifying traumatic abdominal injuries. fox et al. showed that the presence of positive fast findings is a proper predictor for presence of intra-abdominal injury (16). additionally, kelley et al. showed a 73% sensitivity and 100% specificity for fast in identification of intra-abdominal traumatic injuries (17). in the present study, the number of false positive cases of fast was high (31.1%). one of the reasons might be that accuracy of sonography has a significant correlation with the operator’s skill. since in this study, fast was performed by an emergency medicine resident, his skill and experience might have affected the interpretation of fast data. one of the limitations of this study was its short followup duration. if long-term follow-up for 1, 6, or 12 months was done, factors affecting long-term outcome such as mortality or need for delayed surgery could be evaluated. another limitation was performance of sonography by an emergency medicine resident. although a sonography workshop was held for the resident, his lack of skill could affect the results. conclusion: based on the results of the present study, only 68.9% of the positive fast findings in patients with blunt abdominal trauma and stable hemodynamics was confirmed by abdominopelvic ct scan. finally, only 6.6% of these patients needed laparotomy. simultaneous presence of free fluid and air in the abdominal area, old age, and higher grading o solid organ injuries were factors that had a significant correlation with need for laparotomy. acknowledgments: authors would like to thank all the staff of ed of poursina hospital, rasht, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. miniño am, heron mp, murphy sl, kochanek kd. deaths: final data for 2004. natl vital stat rep. 2007;55:1-119. 2. hofman k, primack a, keusch g, hrynkow s. addressing the growing burden of trauma and injury in low-and middleincome countries. am j public health. 2005;95(1):13-7. 3. sabzghaba a, shojaee m, safari s, hatamabadi hr, shirvani r. the accuracy of urinalysis in predicting intra-abdominal injury following blunt traumas. emergency. 2015;3:[in press]. 4. chardoli m, rahimi-movaghar v. analysis of trauma outcome at a university hospital in zahedan, iran using the triss method. east afr med j. 2006;83(8):440-2. 5. shojaee m, faridaalaee g, yousefifard m, et al. new scoring system for intra-abdominal injury diagnosis after blunt table 2: the relationship of baseline characteristics and clinical findings with need for laparotomy factors laparotomy p yes (n = 12) no (n = 168) age 36.8±11.4 27.3±11.4 0.006 sex male 10 (83.3) 128 (76.2) 0.57 female 2 (16.7) 40 (23.8) hemoglobin (mg/dl) 13.0±1.8 12.2±1.7 0.12 grade of ruptured spleen i 0 (0.0) 18 (64.3) 0.001 ii 1 (25.0) 9 (32.1) iii 1 (25.0) 1 (3.5) v 2 (50.0) 0 (0.0) grade of hepatic rupture i 0 (0.0) 7 (13.7) 0.038 ii 0 (0.0) 32 (62.8) iii 0 (0.0) 11 (21.6) iv 1 (100.0) 1 (2.0) presence of air and fluid no 5 (41.7) 168 (100.0) <0.001 yes 7 (58.3) 0 (0.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 139 emergency (2016); 4 (3): 136-139 trauma. chin j traumatol. 2014;17(1):19-24. 6. scalea tm, rodriguez a, chiu wc, et al. focused assessment with sonography for trauma (fast): results from an international consensus conference. j trauma acute care surg. 1999;46(3):466-72. 7. soundappan s, holland a, cass d, lam a. diagnostic accuracy of surgeon-performed focused abdominal sonography (fast) in blunt paediatric trauma. injury. 2005;36(8):970-5. 8. patel jc, tepas j. the efficacy of focused abdominal sonography for trauma (fast) as a screening tool in the assessment of injured children. j pediatr surg. 1999;34(1):447. 9. chiu wc, cushing bm, rodriguez a, et al. abdominal injuries without hemoperitoneum: a potential limitation of focused abdominal sonography for trauma (fast). j trauma acute care surg. 1997;42(4):617-25. 10. allen cj, tashiro j, sola je. role of fast or abdominal ultrasound to limit ct imaging in evaluation of the pediatric abdominal trauma patient. curr surg report. 2014;2(6):1-5. 11. ben-ishay o, daoud m, peled z, brauner e, bahouth h, kluger y. focused abdominal sonography for trauma in the clinical evaluation of children with blunt abdominal trauma. world j emerg surg. 2015;10(1):27. 12. wu c-y, yang s-j, fu c-y, et al. the risk factors of concomitant intraperitoneal and retroperitoneal hemorrhage in the patients with blunt abdominal trauma. world j emerg surg. 2015;10(1):4. 13. cunningham ma, tyroch ah, kaups kl, davis jw. does free fluid on abdominal computed tomographic scan after blunt trauma require laparotomy. j trauma acute care surg. 1998;44(4):599-603. 14. yanar h, ertekin c, taviloglu k, kabay b, bakkaloglu h, guloglu r. nonoperative treatment of multiple intraabdominal solid organ injury after blunt abdominal trauma. j trauma acute care surg. 2008;64(4):943-8. 15. haan jm, bochicchio gv, kramer n, scalea tm. nonoperative management of blunt splenic injury: a 5-year experience. j trauma acute care surg. 2005;58(3):492-8. 16. fox jc, boysen m, gharahbaghian l, et al. test characteristics of focused assessment of sonography for trauma for clinically significant abdominal free fluid in pediatric blunt abdominal trauma. acad emerg med. 2011;18(5):477-82. 17. kelley sr, tsuei bj, bernard ac, boulanger br, kearney pa, chang pk. the effectiveness of focused assessment with sonography for trauma in evaluating blunt abdominal trauma with a seatbelt mark sign. j curr surg. 2014;4(1):17-22. archives of academic emergency medicine. 2022; 10(1): e60 le t t e r to ed i to r monkeypox outbreak in non-endemic areas: will it cause a new pandemic? a letter to editor mostafa alavi-moghaddam1∗ 1. emergency medicine department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. received: june 2022; accepted: june 2022; published online: 25 july 2022 cite this article as: alavi-moghaddam m. monkeypox outbreak in non-endemic areas: will it cause a new pandemic? a letter to editor. arch acad emerg med. 2022; 10(1): e60. https://doi.org/10.22037/aaem.v10i1.1706. dear editor; monkeypox (mp) is a rare endemic infection found in tropical rainforest areas of west or central africa. the recent world health organization (who) reports of confirmed mp cases from non-endemic areas have raised global concern over the risk of a new pandemic. monkeypox is a misnomer, as the first confirmed case of mp was diagnosed in a monkey in 1958; however, mp virus is a viral zoonosis that belongs to orthopoxvirus genus of the poxviridea family and in addition to old and new world monkeys and apes, it can infect rats, mice, squirrels, prairie dogs, and rabbits (1). mp virus can be transmitted through touching blood, body fluids, spots, blisters or scabs of infected animals or infected persons. mp virus is also spread through touching the clothing, bedding, or towels of infected persons. face to face exposure to infected persons and eating raw or under-cooked meat from infected animals are other sources of infection (2). according to the report of european center for disease prevention and control (ecdc) on 15 june 2022, confirmed non-endemic cases of mp have increased to 1158 cases in 22 eu/eea countries and 724 cases in 13 non-eu/eea countries. most of those cases have been found in young men and almost all of the patients are men who have had sex with men (1). monkeypox is usually a mild and self-limiting disease. the symptoms usually present within 2 weeks of exposure to the sources of infection and typically include fever, headache, sore throat, swollen lymph nodes, and rash evolving from macules to vesicles and eventually becoming pustules. the symptoms last from 2-4 weeks. mild mp cases only need to be isolated at home to prevent transmission of disease to the healthy people. in special hosts (immunocompromised in∗corresponding author: mostafa alavi-moghaddam; emergency medicine department, imam hossein hospital, shahid madani ave., tehran, iran. email: mosalavi@sbmu.ac.ir, tel: 00989122967248, orcid: https://orcid.org/0000-0002-7176-023x. dividuals, pregnant women, infants, and young children) the severity of mp symptoms is higher and the outcome may be poor. the severe cases of mp may need antiviral treatment (i.e. tecovirimat), which is not globally affordable yet (3). the health care workers (hcws) who examine or practice with a suspected case of mp should appropriately use infection prevention and control measures including personal protective equipment (ppe) (medical mask, gloves, gown, eye protection by goggle or face shield) and hand hygiene. ppe should be disposed prior to leaving the isolation area, where the patient is admitted. hcws must use a respirator (ffp2 or n95) if the patient needs urgent aerosol generating procedures (i.e. aspiration or open suctioning of respiratory tract specimen, bronchoscopy, intubation, cardiopulmonary resuscitation). those who have unprotected exposures to patients with monkeypox do not need to leave work duty if asymptomatic, but should undergo close examination for symptoms, which includes measurement of temperatures at least twice daily for 21 days following the exposure. each day, these hcws should be checked regarding evidence of any relevant signs/symptoms as mentioned above. post-exposure mp vaccination (ideally within 4 days of exposure) may be considered in immunocompromised or pregnant hcws. prompt isolation of suspected or confirmed cases in a single room with adequate ventilation, dedicated bathroom, and staff using appropriate protection gear is recommended. grouping (confirmed with confirmed, suspected with suspected) can be implemented if single rooms are not available, ensuring minimum of 1-meter distance between patients. isolation and transmission-based precautions should be continued until resolution of symptoms. in the current epidemiologic context of mp, clinicians should immediately report suspected cases of mp to the national or local public health authorities and probable and confirmed cases should immediately be reported to who by national health authorities. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. alavi-moghaddam 2 monkeypox does not spread easily between people without close contact and that is why the mp threat is potentially low (4); thus, at this time, who does not recommend any international travel-related measures for incoming or outgoing travelers. however, who and ecdc have recently published a joint technical report and guidance on navigating monkeypox during the summer season for national health authorities (5). 1. declarations 1.1. acknowledgments none. 1.2. funding and supports none to declare. 1.3. conflict of interest none to declare. references 1. ecdc. monkeypox multi-country outbreak 15 june 2022 [available from: https://www.ecdc.europa.eu. 2. uk nhs. monkeypox 2022 [available from: https://www.nhs.uk/conditions/monkeypox/. 3. beusekom mv. antivral drug may limit monkeypox symptom duration, infectiousness. cidrap news [internet]. 2022. available from: https://www.cidrap.umn.edu/newsperspective/2022/05/antiviral-drug-maylimit-monkeypox-symptom-durationinfectiousness#: :text=a%20study%20on%20the%20use,of %20monkeypox%20outside%20of%20africa. 4. cdc. monkeypox 2022 [available from: https://www.cdc.gov/poxvirus/monkeypox/index.html. 5. who. multi-country monkeypox outbreak in nonendemic countries 2022 [21 may 2022:[available from: https://www.who.int/emergencies/disease-outbreaknews/item/2022-don385. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency 2016; 6 (4): 192-195 or i g i n a l re s e a rc h comparing two different doses of intravenous midazolam in pediatric sedation and analgesia hassan barzegari1, arash forouzan1, kambiz masoumi1∗, hassan motamed1, behzad zohrevandi2, shima zeynadini meymand1 1. department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. road trauma research center, guilan university of medical sciences, rasht, iran. received: may 2015; accepted: september 2015 abstract: introduction: midazolam has turned into a common drug for pediatric procedural sedation and analgesia. however, there is not much data regarding its proper dose and potential side effects in the iranian children population. therefore, the present study was done to compare 2 doses of iv midazolam in this regard. methods: the present clinical trial was performed to compare 0.1 and 0.3 m g /k g doses of iv midazolam in induction of sedation for head trauma infant patients in need of brain computed tomography (ct) scan. conscious infants under 2 years old, with stable hemodynamics were included. onset and duration of action as well as probable side effects were compared between the two groups using spss version 22. results: 110 infants with the mean age of 14.0 ± 5.9 months (range: 4–24) and mean weight of 9.7 ± 2 k g (range: 5–15) were randomly allocated to one of the 2 study groups (54.6% female). success rate in 0.1 and 0.3 m g /k g groups were 38.2% (21 patients) and 60% (33 patients), respectively (p = 0.018). overall, 56 (50.9%) patients did not reach proper sedation and were sedated receiving ketamine (22 patients) or another dose of midazolam (34 patients, mean additional dose needed was 2.1±1.1 m g ). conclusion: the results of the present study demonstrated the higher success rate and longer duration of action for 0.3 m g /k g midazolam compared to 0.1 m g /k g . the groups were equal regarding onset of action, effect on vital signs and probable side effects. keywords: midazolam; conscious sedation; dose-response relationship, drug; infant; emergency service, hospital © copyright (2016) shahid beheshti university of medical sciences cite this article as: barzegari h, forouzan a, masoumi k, motamed h, zohrevandi b, zeynadini meymand sh. comparing two different doses of intravenous midazolam in pediatric sedation and analgesia. emergency. 2016; 4(4):192-195. 1. introduction s edation induction is one of the most important and sometimes most difficult stages of carrying out a diagnostic or therapeutic procedure in children (1). children not cooperating for diagnostic evaluations such as computed tomography (ct) scan and magnetic resonance imaging are among the most common cases of using procedural sedation and analgesia (psa) in emergency departments (ed). an ideal sedative drug should be rapid and shortacting, with minimum side effects on the patients respiratory condition and hemodynamic. various drugs such as chloral hydrate, phenobarbital, propo∗corresponding author: department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, azadegan avenue, ahvaz, khuzestan province 6193673166, iran; tel/fax: +986112229166; email: emdajums@yahoo.com. fol, midazolam, and etomidate are among the available drugs for this purpose yet, selection of the safest and most efficient drug and its proper dose for sedation are a matter of debate (1–4). many of pediatric patients do not receive enough drug due to concerns about probable side effects of the drug (5). midazolam has turned into a common drug for induction of sedation in eds as a result of its short half-life, various methods of prescription and less pain at the time of injection. this relatively short-acting benzodiazepine has anti-stress, sedative, anti-seizure, and muscle relaxant effects. singh et al. showed that use of intravenous (iv ) midazolam with a 0.2 m g /k g dose, can induce proper sedation with minimum side effects for pediatric imaging (6). however, there is not much data regarding its proper dose and potential side effects especially in the iranian children population. therefore, the present study was done to compare 2 doses of iv midazolam in sedation induction for doing brain imaging in infants. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com emdajums@yahoo.com 193 emergency 2016; 6 (4): 193-195 2. methods 2.1. study design the present clinical trial was performed to compare 0.1 and 0.3 m g /k g doses of iv midazolam in induction of sedation for infants in need of brain ct scan following head trauma. the infants presented to the ed of golestan and imam khomeini hospitals, ahvaz, iran, during april 2014 to march 2015 were studied. after completely explaining the study protocol to the parents, informed consent form was filled for each participant to enter the study. all the researchers adhered to helsinki declaration. if the parents were not content with the study process or did not want their infant to continue participating at any stage, the infant was excluded. the present study has been registered on the iranian registry of clinical trials (irct) under the number irct201592121289n2 and approved by the ethics committee of ahvaz jundishapour university of medical sciences. 2.2. participants infants presented to the ed following head trauma in need of sedation induction for undergoing brain ct scan were enrolled. conscious infants under 2 years old, with stable hemodynamics were included. exclusion criteria consisted of high probability of difficult airway, history of uremia and allergy to benzodiazepine, presence of hemodynamic instability, congestive heart failure, liver diseases, decreased level of consciousness, uncontrolled vomiting, history of reflux, and simultaneous use of opioids. 2.3. procedure all patients were prepared with a proper peripheral iv line and continuous heart, blood pressure, pulse rate, and pulse oximetry monitoring. participants underwent low-flow oxygen therapy via nasal cannula during the procedure. they were divided into equal groups of a and b, using 4-block randomization. group a, received iv midazolam with 0.1 m g /k g dose, while the dose was 0.3 mg/kg for group b. the goal was reaching sedation level of 3 or 4 based on ramsay scale (7). not reaching the desired level of sedation was considered as sedation failure. in these cases iv ketamine with 1 m g /k g dose or another dose of midazolam was used. all injections were done via the peripheral vessel using a blue or yellow angiocatheter, and slowly during 10 seconds. brain ct scan indication was decided by an emergency medicine specialist based on the standard protocols of advanced trauma life support (atls). injections were done by trained nurses under supervision of a senior emergency medicine resident. over the course of the procedure, all the required equipment for probable need for airway management were present at the patients bedside. midazolam ampule containing 5 m g /c c was used. we should note that the physician prescribtable 1: baseline characteristics of studied patients variable groups p value 0.1 m g /k g 0.3 m g /k g sex boy 26 (47.3) 24 (43.6) < 0.424 girl 29 (52.7) 31 (56.4) age (month) 15.7 ± 5.4 12.4 ± 6.0 0.003 weight (k g ) 9.8 ± 1.9 9.5 ± 2.0 0.465 the number of patients in each group = 55; measures presented as number (%) or mean ± standard deviation. ing the drugs and the patientsâăź parents were blinded to the drug dose. 2.4. data gathering a checklist consisting of demographic data and pharmacodynamics (onset and duration of action and side effects) was filled for all the patients in both groups. drop of oxygen saturation to < 95, decreased blood pressure, inconsolable crying, restlessness and anxiety, hiccup, opisthotonus, seizure, nausea and vomiting, and respiratory depression and apnea were among the studied side effects. 2.5. statistical analysis data were analyzed using spss statistical software version 22. quantitative data were reported as frequency and percentage, and qualitative ones as mean ± standard deviation. chisquare and independent sample t-test were used for comparing data between two groups. p < 0.05 was considered as significance level. 3. results 110 infants with the mean age of 14.0 ± 5.9 months (range: 4–24) and mean weight of 9.7 ± 2 k g (range: 5–15) were randomly allocated to one of the 2 study groups (54.6% female). table 1 shows the baseline characteristics of the patients. success rate in 0.1 and 0.3 m g /k g groups were 38.2% (21 patients) and 60% (33 patients), respectively (p = 0.018). overall, 56 (50.9%) patients did not reach proper sedation and were sedated receiving ketamine (22 patients) or another dose of midazolam (34 patients, mean additional dose needed was 2.1 ± 1.1 m g ). table 2 compares the therapeutic characteristics and side effects of the 2 doses of midazolam. 4. discussion the results of the present study demonstrated the higher success rate and longer duration of action for 0.3 m g /k g midazolam compared to 0.1 m g /k g . the groups were equal regarding onset of action, effect on vital signs and probable side effects. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com barzegari et al. 194 table 2: baseline characteristics of studied patients variable groups p value 0.1 m g /k g 0.3 m g /k g sex boy 26 (47.3) 24 (43.6) < 0.424 girl 29 (52.7) 31 (56.4) age (month) 15.7 ± 5.4 12.4 ± 6.0 0.003 weight (k g ) 9.8 ± 1.9 9.5 ± 2.0 0.465 the number of patients in each group = 55; measures presented as number (%) or mean ± standard deviation. facing children in ed has always been special. presentation of a pediatric trauma patient, accompanied by restless parents, to an overcrowded ed has been a nightmare for emergency medicine physicians, especially if a diagnostic and therapeutic procedure is required. the need for keeping the child motionless during procedures, has made using psa inevitable for this age group. being familiar with various kinds of available drugs and their dosage is a necessary skill for all emergency physicians. therefore, the present study was designed and carried out to compare the effectiveness and side effects of two different iv midazolam doses. in the study by singh et al., midazolam’s onset of action was shorter than this study (6). this difference may be due to the differences in age distribution of the participants in the 2 studies and the chief complaints on admission. in both studies, a relatively significant number of the patients needed additional doses to reach proper sedation and a single dose of the drug had a significant failure rate. in addition, in a study by sutherland et al., use of 0.2 m g /k g alone was not enough to induce proper sedation for undergoing ct scan in most children; it was efficient for only 19% of them (2). regarding onset of action, the results of the present study were in line with those of jevdjic et al. in their 2011 study, especially in the 0.1 m g /k g dose (8). additionally, regarding probable side effects and effects on vital signs a thorough correlation was seen between the results of this study and rahman study (9). treatment success rate in this study was less than 50% for both doses. this means that about half the patients need higher doses of midazolam or other drugs such as ketamine to reach the proper level of sedation. the results of a review study in 2007 showed that despite the similar effects of midazolam and ketamine, ketamine was the drug of choice for both parents and physicians to sedate children (10). therefore, it seems that although midazolam is safe and emergency physicians are familiar with its probable side effects, its success rate, at least with the doses mentioned in the present study, is not high. therefore, we should either revise the dose of this drug, or use other drugs with higher success probability. the importance of this matter is that most of the time, when children are not sedated with the initial injection, it makes the parents more anxious and therefore makes the atmosphere more chaotic. it is suggested to carry out other trials with various doses and bigger sample size, to find the proper dose of drug. parents not being content about their children participating in the study was among the limitations of the present study, which made case collection somehow difficult. 5. conclusion the results of the present study demonstrated the higher success rate and longer duration of action for 0.3 m g /k g midazolam compared to 0.1 m g /k g . the groups were equal regarding onset of action, effect on vital signs and probable side effects. 6. appendix 6.1. acknowledgements this article was extracted from the emergency medicine residency thesis of dr. shima zeynadini meymand. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding this article is extracted from a project funded by jundishapour university of medical sciences, which was registered under the number gp93044. 6.4. conflict of interest none. references 1. lgren jt, algren cl. sedation and analgesia for minor pediatric procedures. pediatric emergency care. 1996;12(6):435–41. 2. moro-sutherland dm, algren jt, louis pt, kozinetz ca, shook je. comparison of intravenous midazolam with pentobarbital for sedation for head computed tomography imaging. academic emergency medicine. 2000;7(12):1370–5. 3. thompson j, schneider s, ashwal s, holden b, hinshaw jr d, hasso a. the choice of sedation for computed tomography in children: a prospective evaluation. radiology. 1982;143(2):475–9. 4. yaster m, nichols dg, deshpande jk, wetzel rc. midazolam-fentanyl intravenous sedation in chilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 195 emergency 2016; 6 (4): 195-195 dren: case report of respiratory arrest. pediatrics. 1990;86(3):463–7. 5. sievers td, yee jd, foley me, blanding pj, berde cb. midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters. pediatrics. 1991;88(6):1172–9. 6. singh r, kumar n, vajifdar h. midazolam as a sole sedative for computed tomography imaging in pediatric patients. pediatric anesthesia. 2009;19(9):899–904. 7. ramsay m, savege t, simpson b, goodwin r. controlled sedation with alphaxalone-alphadolone. british medical journal. 1974;2(5920):656. 8. jevd̄ić j, šurbatović m, drakulić-miletić s, žunić f. deep sedation with midazolam and propofol in children undergoing ambulatory magnetic resonance imaging of the brain. vojnosanitetski pregled. 2011;68(10):842–5. 9. ab rahman nhn, hashim a. is it safe to use propofol in the emergency department? a randomized controlled trial to compare propofol and midazolam. international journal of emergency medicine. 2010;3(2):105–13. 10. munro a, machonochie i. midazolam or ketamine for procedural sedation of children in the emergency department. emergency medicine journal. 2007;24(8):579– 80. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency. 2017; 5 (1): e51 le t t e r to ed i to r urgent need to strengthen the chain of survival in the united arab emirates; a letter to the editor alan michael batt1∗, ahmed saleh mohamed al-hajeri 1, fergal henry cummins1 1. national ambulance llc, abu dhabi, united arab emirates. received: october 2016; accepted: october 2016; published online: 14 january 2017 cite this article as: michael batt a, al-hajeri a, cummins f. urgent need to strengthen the chain of survival in the united arab emirates; a letter to the editor. emergency. 2017; 5(1): e51. f urther to our recently published findings, we have completed the analysis of our second year of prehospital data collection for the same service (1). we wish to expedite the availability of this data to clinicians, researchers and policy makers in the region. our 2015/2016 out-of-hospital cardiac arrest (ohca) data displayed the following demographic results: 514 ohca resuscitation attempts were attended by national ambulance (na) emergency medical services (ems) in the northern emirates region (75% male). male patients continued on average to be younger than female ones (50 vs. 61 years), and the median age of ohca cases in the united arab emirates remains well below that of cases in western countries (52 years, interquartile range: 38; 69). over half of these cases occurred at a home residence, with the next most common location being a street or highway. a total of 282 incidents were witnessed by a bystander, 43 events by na crew, and 189 incidents were not witnessed. bystander cardiopulmonary resuscitation (cpr) was attempted in 135 (28.6%) of non-ems-witnessed cases (n=471). a bystander or public access defibrillator was applied in only five cases (1%) and no shocks were delivered by bystanders in any case. a total of 34 (6.6%) patients had a return of spontaneous circulation in the pre-hospital setting, over twice the rate demonstrated in the first year of our study. survival to discharge data has been collected for the first time by our hospital partners, and the publication of these results in the near future will contribute greatly to our understanding of the ohca issue in the region. the increase in the number of ohca responses by na crew is notable in our findings. this may be attributable to several reasons, including greater public awareness of ems capabili∗corresponding author: alan michael batt; etihad towers, level 6 tower 3, abu dhabi, united arab emirates. email: batt.alan@gmail.com, tel: +971-25968600 ties, and improved access to ems via the dedicated 998 emergency number and the na mobile application. this trend is to be welcomed, as implementation of the chain of survival increases the odds for survival (2). however, similar to our previous findings, a large number of the cases that were witnessed still had a significant time lapse before ems was activated. a chain is only as strong as its weakest link. as such, increasing public awareness of the need for early ems activation, improving bystander cpr rates, and increasing the availability of public access defibrillators still remain significant challenges in implementing the chain of survival in full to address this public health issue in the united arab emirates. references 1. batt a, al-hajeri a, cummins f. a profile of out-ofhospital cardiac arrests in northern emirates, united arab emirates. saudi med j. 2016;37(11):179–86. 2. cummins ro. emergency medical services and sudden cardiac arrest: the “chain of survival” concept. annu rev public health. 1993;14:313–33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references emergency. 2017; 5 (1): e71 ca s e re p o rt concurrent hand and penile gangrene following prolonged warfarin use; a case report fatemeh mahdizadeh1, saeed safari2∗ 1. department of emergency medicine, ilam university of medical sciences, ilam, iran. 2. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. received: march 2017; accepted: june 2017; published online: 21 june 2017 abstract: warfarin induced skin necrosis (wisn) is a rare but important side effect of warfarin. early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. so, physicians should be aware of such a complication. screening for protein c or s or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (inr). here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin. keywords: warfarin; penile diseases; gangrene; anticoagulants; necrosis; extremities © copyright (2017) shahid beheshti university of medical sciences cite this article as: mahdizadeh f, safari s. concurrent hand and penile gangrene following prolonged warfarin use; a case report. emergency. 2017; 5 (1): e71. 1. introduction warfarin is widely used as an anticoagulant agent. warfarin induced skin necrosis (wisn) is an uncommon but serious condition, occurring in 1:10000 patients who receive this drug, with a female/male ratio of 1:4 (1). skin necrosis has been reported in 0.17% of patients affected with side effects of warfarin (2, 3). the majority of cases present in the first month of treatment, but late onset wisn may also occur up to 15 years after starting the treatment (4, 5). in this report we describe a patient who had developed late onset warfarininduced skin necrosis, concurrently in acral and penile area. 2. case presentation: the patient was a 54-years-old male presented with penis and right upper extremity pain, black discoloration and swelling for the past two days. the patient was a known and treated case of deep vein thrombosis from 6 years before and he was taking warfarin intermittently during this time. he was opium addicted. the patient was a cachectic man. he was completely alert (gcs =15). on ar∗corresponding author: saeed safari; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel: +989128251535; email: safari266@gmail.com rival to the emergency department, pulse rate was 90 per minute, respiratory rate was 18 per minute, blood pressure was 115/70 mmhg and body temperature was 37.8 ◦c. distal part (about one third) of his right forearm was swollen, tender and black discolored and a bulla around the wrist was seen. right lower extremity was edematous. distal pulses of lower limbs were palpable but diminished because of edema. also the penis was extremely tender, swollen, erected and dark discolored. figure 1 shows the patient’s lesions. his primary lab results were as follows: white blood cell=6500 cells/µl, hemoglobin=6.8 gr/dl, hematocrit =20.3, platelet=269000 cells/µl, prothrombin time (pt) =28 s, partial thromboplastin time (ptt)=43 s, international normalized ratio (inr)=4.6, blood urea nitrogen=10 mg/dl, creatinine=0.7 mg/dl, calcium=8 mg/dl, phosphorous=2.7 mg/dl, total protein=3.9 mg/dl, albumin=1.8 mg/dl, aspartate aminotransferase (ast)=16 u/l, alanine aminotransferase (alt)=13 u/l, lactate dehydrogenase (ldh)=429 u/l, creatine phosphokinase (cpk)=83 u/l. hbs-ag, hcvab and hiv-ab were all reported as negative. ultrasonography of right hand revealed subcutaneous edema and fluid collection. a hematoma was reported in dorsal area at the level of first metacarpophalangeal joint. arterial and venous duplex of right upper extremity were normal. also ct angiography of aorta to distal of right upper limb was normal without cut off. ultrasonography of testicles revealed right this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. mahdizadeh and s. safari 2 figure 1: patient’s lesions in the right upper and lower extremities as well as penis. extra-testicular hematoma, left atrophic testis and edema of scrotum. duplex of both testicles were normal. warfarin was discontinued and correction of coagulation tests was done by replacement of fresh frozen plasma and vitamin k. also cefazolin was ordered intravenously every 8 hours and 16-french foley catheter was fixed. partial penectomy and urethroplasty of anterior duct was done approximately two months after admission and then amputation of right hand above the wrist was performed. histological findings of portion of penile shaft confirmed subtotal necrosis and areas of old and fresh hemorrhage and hematoma. the patient was stable and discharged four days after surgery. surgeons advised him to follow up in clinic. in our patient neither antiphospholipid antibodies nor low levels of protein c or s were measured and nor heparin induced thrombocytopenia (hit) was considered. 3. discussion wisn begins as localized paresthesia with an erythematous flush, progresses to petechial and hemorrhagic bulla and may eventually result in full thickness necrosis (6). it usually involves areas with more subcutaneous fat content such as breasts, thighs, and buttocks (5, 7). although the pathogenesis of the disease is still unknown, there were numerous reports of inherited or functional deficiency of protein c, protein s or factor v leiden, antithrombin iii, hyperhomocysteinemia or in association with hit and anti-phospholipid syndrome. another theory for explaining the pathophysiology of wisn is hypersensitivity reaction or a direct toxic effect (1, 2, 8). obesity, premenopausal age, viral infections, hepatic disease, and drug interactions are mentioned as predisposing factors (1). the lesions must be differentiated from necrotizing fasciitis, venous gangrene, decubitus ulcer, and hematoma that are more common (1, 2). wisn is usually diagnosed clinically, based on patient’s symptoms, lesion appearance and history of recent warfarin therapy (4). determining protein c and s levels for assessing predisposing factors and skin biopsy can aid in diagnosis. histology typically shows diffuse microthrombosis within dermal and subcutaneous capillaries, venules and deep veins, with endothelial cell damage resulting in ischemic skin necrosis and red blood cell extravasation (9). the lack of perivascular inflammation and arteriolar thrombosis, differentiates wisn from the vasculitis (4, 9). treatment includes discontinuing warfarin, although it has not been shown to alter outcome, starting heparin, administrating vitamin k, fresh frozen plasma (ffp) or pure activated protein c because of its low level. longterm treatment includes local wound care and observation of the wound until healing. skin grafting, surgical debridement and amputation may be necessary in severe limb gangrene (4, 8). wisn should be suspected in all patients who undergo over-warfarinization, even with an initially normal coagulation profile. prompt diagnosis and discontinuation of warfarin are crucial for the prognosis (1, 3). necrosis may be prevented by identifying high risk patients and avoiding high dose of warfarin in high risk patients (1, 10). several recommendations for preventing wisn have been advanced: 1) heparin should be continued until the inr is near the therapeutic range as a result of the warfarin therapy and vitamin k dependent clotting factors have been consumed; 2) standard or low dose warfarin should be used instead of initial large loading doses; 3) a clinician should be cautious when advancing the dosage of warfarin (6). 4. conclusion: wisn, while rare, is an important complication following warfarin administration. therefore, physicians should be aware. screening for protein c or s or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, avoiding high inr level and finally, early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e71 5. appendix 5.1. acknowledgements the authors would like to thank the emergency department staff of shohadaye tajrish hospital, tehran, iran. 5.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest none. 5.4. funding none. references 1. kakagia d, papanas n, karadimas e, polychronidis a. warfarin-induced skin necrosis. annals of dermatology. 2014;26(1):96-8. 2. chan y, valenti d, mansfield a, stansby g. warfarin induced skin necrosis. british journal of surgery. 2000;87(3):266-72. 3. murad aa, daly t, mulligan n, lenane p. extensive warfarin-induced skin necrosis successfully treated with negative pressure wound therapy. bmj case reports. 2014;2014:bcr2013203510. 4. choudhary s, madnani a, singh a. late onset warfarin induced skin necrosis in human immunodeficiency virus infected patient with pulmonary tuberculosis. indian journal of sexually transmitted diseases. 2013;34(1):47-9. 5. kozac n, schattner a. warfarin-induced skin necrosis. journal of general internal medicine. 2014;29(1):248-9. 6. alves d, chen i. warfarin-induced skin necrosis. hospital physician. 2002;38(8):39-42. 7. miura y, ardenghy m, ramasastry s, kovach r, hochberg j. coumadin necrosis of the skin: report of four patients. annals of plastic surgery. 1996;37(3):332-7. 8. khalid k. warfarin-induced necrosis of the breast: case report. journal of postgraduate medicine. 2003;50(4):268-9. 9. nazarian r, van cott e, zembowicz a, duncan l. warfarin-induced skin necrosis. journal of the american academy of dermatology. 2009;61(2):325. 10. pourdeyhimi n, bullard z. warfarin-induced skin necrosis. hospital pharmacy. 2014;49(11):1044-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion conclusion: appendix references archives of academic emergency medicine. 2022; 10(1): e67 le t t e r to ed i to r is monkeypox a concern in multiple sclerosis patients? a letter to editor elnaz asadollahzadeh1, fereshteh ghadiri1, zahra ebadi1, abdorreza naser moghadasi1∗ 1. multiple sclerosis research center, neuroscience institute, tehran university of medical sciences, tehran, iran. received: june 2022; accepted: july 2022; published online: 18 august 2022 cite this article as: asadollahzadeh e, ghadiri f, ebadi z, naser moghadasi a. is monkeypox a concern in multiple sclerosis patients? a letter to editor. arch acad emerg med. 2022; 10(1): e67. https://doi.org/10.22037/aaem.v10i1.1729. dear editor: individuals with autoimmune conditions have been characterized as the population very much prone to illness. this is because of the way various diseases impact their immune system, and because immunosuppressant medications were employed to cure the majority of these ailments (1). by weakening the immune system, these drugs allow the control of many autoimmune disorders such as multiple sclerosis. patients with multiple sclerosis who use these drugs are in danger of developing a weak immune system and a wide range of infectious diseases such as herpesvirus infections (2). viral, bacterial, and fungal infections can cause ms exacerbations (3). monkeypox, a virus that resembles smallpox, was first found in captive primates in 1958 and in individuals in the republic of congo in 1970 (4). monkeypox virus is an evolving zoonotic orthopoxvirus (opxv ) that can cause a severe and transmittable human disease, potentially posing threats to public health (5). the most prevailing reason for the emergence of monkeypox cases has been diminishing immunity. there are currently no specific treatments for monkeypox disease, yet outbreaks can be managed (6). those with a compromised immune system, may be at a higher risk for complications if infected, in spite of vaccination (7). people with weakened immune systems are much more susceptible to lethal forms of the disease. when compared to other people, patients with autoimmune conditions, such as ms, have a 3-20-fold greater risk of catching smallpox (8). in the meantime, people with extreme immunodeficiency should not be analyzed or clinically treated for symptoms suggestive of monkeypox (9). the authors’ examination of the literature on past and ∗corresponding author: abdorreza naser moghadasi; multiple sclerosis research center, sina hospital, hassan abad square, tehran, iran. e-mail: abdorrezamoghadasi@gmail.com, tel: +98 21 66348571, fax: +98 21 66348571, orcid: https://orcid.org/0000-0002-8598-0911. present experiences with monkeypox in multiple sclerosis patients was spurred by the recent epidemic of monkeypox. while the consequences of monkeypox in patients with ms are unknown, the danger of contracting this lethal illness surpasses the chance of ms relapse. there is compelling evidence that an infectious episode increases the chance of ms aggravation. as a result, it is preferable to keep track of ms patients on a frequent basis in order to avoid problems. evidence backs up 1) methods to reduce the risk of contracting infectious diseases that might cause ms exacerbations, and 2) the safety of vaccinations in ms patients. the mandated precautions should be observed in ms patients to avoid this infection. despite the fact that this virus is conveyed through contact with suspected cases, people on immunosuppressive medicines are still at risk of the illness. the high rate of infections when taking immunesuppressants highlights the significance of carefully weighing the risks and benefits of various immune-modifying medications. adverse events due to infections were reduced in patients taking immunosuppressant medications for ms after a risk mitigation program that included infectious disease consulting and standardized screening and preventive measures. declarations acknowledgments none. authors’ contributions elnaz asadollahzadeh and abdorreza naser moghadasi: literature search, manuscript preparation, manuscript editing and manuscript review. fereshteh ghadiri and zahra ebadi: manuscript preparation and manuscript editing. all authors read and approved final version of manuscript. funding and supports none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. asadollahzadeh et al. 2 conflict of interest the authors declare that they have no conflict of interest. references 1. assessment rr. monkeypox multi-country outbreak. 2022. http://www.sepexpal.org/wpcontent/uploads/2022/05/23-mayo.-ecdc.-monkeypoxmulti-country-outbreak.pdf 2. lebrun c, vukusic s. immunization and multiple sclerosis: recommendations from the french multiple sclerosis society. mult scler relat disord. 2019;31:173-88. 3. castelo-branco a, chiesa f, conte s, bengtsson c, lee s, minton n, et al. infections in patients with multiple sclerosis: a national cohort study in sweden. mult scler relat disord. 2020;45:102420. 4. rezza g. emergence of human monkeypox in west africa. lancet infect dis. 2019;19(8):797-9. 5. yinka-ogunleye a, aruna o, ogoina d, aworabhi n, eteng w, badaru s, et al. reemergence of human monkeypox in nigeria, 2017. emerg infect dis. 2018;24(6):1149. 6. vaughan a, aarons e, astbury j, balasegaram s, beadsworth m, beck cr, et al. two cases of monkeypox imported to the united kingdom, september 2018. euro surveill. 2018;23(38):1800509. 7. rao ak, petersen bw, whitehill f, razeq jh, isaacs sn, merchlinsky mj, et al. use of jynneos (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the advisory committee on immunization practices—united states, 2022. mmwr morb mortal wkly rep. 2022;71(22):734. 8. bisanzio d, reithinger r. keep calm and carry on: projected case burden and duration of the 2022 monkeypox outbreak in non-endemic countries. medrxiv. 2022. 9. mahase e. monkeypox: healthcare workers will be offered smallpox vaccine as uk buys 20 000 doses. bmj.2022;377:o1379. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 29 emergency (2016); 4 (1): 29-33 original research diagnostic accuracy of ultrasonography and radiography in initial evaluation of chest trauma patients ali vafaei1, hamid reza hatamabadi2, kamran heidary1, hosein alimohammadi2, mohammad tarbiyat2* 1. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine , imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mohammad tarbiyat; emergency department, loghman hakim hospital, kamali street, karegar avenue, tehran, iran. tel: +989133089597 / fax: +982155415539 / e-mail: mohammadtarbiat@yahoo.com received: april 2015; accepted: june 2015 abstract introduction: application of chest radiography for all multiple trauma patients is associated with a significant increase in total costs, exposure to radiation, and overcrowding of the emergency department. ultrasound has been introduced as an alternative diagnostic tool in this regard. the aim of the present study is to compare the diagnostic accuracy of chest ultrasonography and radiography in detection of traumatic intrathoracic injuries. methods: in the present prospective cross-sectional study, patients with traumatic intrathoracic injuries, who were referred to the emergency department from december 2013 to december 2014, were assessed. the patients underwent bedside ultrasound, radiographic and computed tomography (ct) scan examinations based on atls recommendations. screening performance characteristics of ultrasonography and radiography were compared using spss 21.0. chest ct scan was considered as gold standard. results: 152 chest trauma patients with a mean age of 31.4 ± 13.8 years (range: 4 ‒ 67), were enrolled (77.6% male). chest ct scan showed pulmonary contusion in 48 (31.6%) patients, hemothorax in 29 (19.1%), and pneumothorax in 55 (36.2%) cases. area under the roc curve of ultrasonography in detection of pneumothorax, hemothorax, and pulmonary contusion were 0.91 (95% ci: 0.86‒0.96), 0.86 (95% ci: 0.78‒0.94), and 0.80 (95% ci: 0.736‒0.88), respectively. area under the roc curve of radiography was 0.80 (95% ci: 0.736‒0.87) for detection of pneumothorax, 0.77 (95% ci: 0.68‒0.86) for hemothorax, and 0.58 (95% ci: 0.5‒0.67) for pulmonary contusion. comparison of areas under the roc curve declared the significant superiority of ultrasonography in detection of pneumothorax (p = 0.02) and pulmonary contusion (p < 0.001). however, the diagnostic value of the two tests was equal in detection of hemothorax (p = 0.08). conclusion: the results of the present study showed that ultrasonography is preferable to radiography in the initial evaluation of patients with traumatic injuries to the thoracic cavity. key words: thoracic cavity; wounds and injuries; diagnostic imaging; ultrasonography; radiography cite this article as: vafaei a, hatamabadi hr, heidary k, alimohammadi h, tarbiyat m. diagnostic accuracy of ultrasonography and radiography in initial evaluation of chest trauma patients. emergency. 2016;4(1):29-33. introduction: trauma is the most important cause of death during the first four decades of life (1). in this context, traumatic intrathoracic injuries comprise 25-40% of mortalities (2). prompt diagnosis of such injuries can decrease mortality and the resultant burden. computed tomography (ct) scan is the gold standard for this diagnosis (3-5). although this diagnostic tool is highly accurate in detection of intrathoracic injuries, patients undergoing ct scan examination receive a high radiation dose (6-8). currently, chest radiography is used as the initial diagnostic tool in these cases. although these techniques are inexpensive and non-invasive, their application for all multiple trauma patients is associated with a significant increase in total costs, exposure to radiation, and overcrowding of the emergency department (9). some recent studies have reported not very high sensitivity and specificity of chest radiography in this regard (10-13). these studies have shown the low diagnostic yield of chest x-rays (6.3‒ 12.4%) in identifying intrathoracic injuries (9, 14-16). during recent years, chest ultrasonography has been introduced as a portable, inexpensive, safe, and fast alternative for radiography in detection of traumatic intrathoracic injuries (17). however, this tool is largely dependent on the experience and expertise of the operator and its results are not very reliable in identifying parenchymal injuries and where no fluid is present (18). based on the above-mentioned points, the present study was designed to compare the diagnostic accuracy of chest ultrasonography and radiography in identifying traumatic intrathoracic injuries. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com vafaei et al 30 methods: study design and setting in the present prospective cross-sectional study, patients with traumatic intrathoracic injuries, who were referred to the emergency department of imam hossein hospital, from december 2013 to december 2014, were assessed. the study was done to calculate the diagnostic accuracy of chest ultrasonography and radiography in the initial evaluation of patients with chest trauma. thoracic ct scan was used as the gold standard. all patients in need for chest ct scan based on standard indications of advanced trauma life support (atls) guidelines were included in a consecutive manner. exclusion criteria consisted of pregnancy, hemodynamic instability, and lack of interest in participating in the study. chest ultrasonography and data collection were carried out by an emergency medicine specialist. chest x-ray and ct scan were reported by two radiologists separately, who were blinded to the clinical findings of patients and aim of study. the protocol of the study was approved by the ethics committee of shahid beheshti university of medical sciences. the researchers adhered to the guidelines of helsinki declaration throughout the study procedures. the protocol of the study did not interfere with the patients’ therapeutic and diagnostic procedures and the patients were not exposed to any risks. the data collection forms were anonymous and a code was assigned to each patient. all the patients submitted an informed consent form before being included in the study. measurements demographic (age, gender, and mechanism of trauma) and clinical data, as well as imaging findings of each patient were recorded using a checklist. immediately after collection of data, the patients underwent chest ultrasonography, which was carried out using a bedside ultrasonography unit (honda, hs 2100) and 3.5-7 mhz linear and curvilinear transducers. examinations were carried out at 2‒6 intercostal spaces on both sides of para-sternal, mid-clavicular, anterior axillary and mid-axillary lines. then, the patients underwent an anterior posterior (ap) chest x-ray examination using a portable x-ray machine (poxible, 100 bp-op) and chest ct scan (siemens, emotion-16, 5-mm-thick slices) in supine position. pneutable 1: baseline characteristics of the studied participants variable frequency percentage age under 18 24 15.8 19‒40 92 60.5 41‒60 27 17.8 over 60 9 6.9 gender male 118 77.6 female 34 22.4 mechanism of trauma penetrating wound 22 14.5 blunt trauma due to accident 93 61.2 blunt trauma due to falling 23 15.1 blunt trauma due to direct impact 14 9.2 subcutaneous emphysema no 133 86.2 yes 21 13.8 crepitation no 131 86.2 yes 21 13.8 trauma to thoracic spinal no 137 90.1 yes 15 9.9 glasgow coma scale 14‒15 96 63.1 9‒13 39 25.7 3‒8 17 11.2 hemodynamic status stable 125 82.2 unstable 27 17.8 this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 31 emergency (2016); 4 (1): 29-33 mothorax, hemothorax, rib fracture, and pulmonary contusion were considered as traumatic intrathoracic injuries. statistical analysis the sample size was calculated to be 139 cases by considering a minimum sensitivity of 98% for the ultrasonography in detection of traumatic intrathoracic injuries and a 30% prevalence rate of pneumothorax in patients with chest trauma (19), at 95% confidence interval (α = 0.05), a power of 90% (β = 0.1) and maximum error of 1% (d = 0.12). data were analyzed with spss 21.0. in order to evaluate the adequacy of radiography and ultrasonography, receiver operating characteristic (roc) curves were drawn and sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive values of radiography and ultrasonography were calculated. significance level was set at p < 0.05. results: 152 chest trauma patients with a mean age of 31.4 ± 13.8 years (range: 4 ‒ 67), were enrolled (77.6% male). table 1 presents baseline characteristics of patients. chest ct scan showed pulmonary contusion in 48 (31.6%) patients, hemothorax in 29 (19.1%), and pneumothorax in 55 (36.2%) cases. table 2 summarizes the screening performance characteristics of chest ultrasonography and radiography in detection of traumatic intrathoracic injuries (pneumothorax, hemothorax, contusion). area under the roc curve of ultrasonography in detection of pneumothorax, hemothorax, and pulmonary contusion were 0.91 (95% ci: 0.86‒0.96), 0.86 (95% ci: 0.78‒ 0.94), and 0.80 (95% ci: 0.736‒0.88), respectively. area under the roc curve of radiography was 0.80 (95% ci: 0.736‒0.87) for detection of pneumothorax, 0.77 (95% ci: 0.68‒0.86) for hemothorax, and 0.58 (95% ci: 0.5‒ 0.67) for pulmonary contusion. comparison of areas under the roc curve declared the significant superiority of ultrasonography in detection of pneumothorax (p = 0.02) and pulmonary contusion (p < 0.001). however, the diagnostic value of the two tests was equal in detection of hemothorax (p = 0.08). discussion: the results of the present study showed that chest ultrasonography had higher diagnostic value in detection of pneumothorax and pulmonary contusion compared to radiography. this value in detection of hemothorax for two studied tools was equal. various studies have evaluated the diagnostic accuracy of ultrasonography in trauma patients (20, 21). in this context, hyacinthe et al. showed that the diagnostic accuracy of ultrasonography was higher than that of chest x-ray. the study showed that the sensitivity and specificity of ultrasonography, compared to ct scan as the gold standard, in diagnosis of thoracic cavity lesions were in the 37‒61% and 61‒ 96% ranges, respectively (22). in the present study, the emergency medicine specialist who carried out ultrasonography examinations was aware of clinical findings table 2: screening performance characteristics of chest ultrasonography and radiography in detection of traumatic intrathoracic injuries in comparison to ct scan index ultrasonography chest x-ray pneumothorax sensitivity 83.6 (70.7‒91.8) 67.3 (53.2‒78.95) specificity 97.9 (92.0‒99.6) 92.7 (85.1‒96.8) positive predictive value 95.8 (84.6‒99.3) 84.1 (69.3‒92.8) negative predictive value 91.3 (83.8‒95.7) 83.2 (74.5‒89.5) positive likelihood ratio 45.6 (10.2‒160.7) 9.2 (4.4‒19.3) negative likelihood ratio 0.17 (0.09‒0.3) 0.35 (0.24‒0.52) hemothorax sensitivity 75.9 (56.1‒90.0) 58.6 (39.1‒75.9) specificity 95.9 (90.3‒98.5) 95.1 (89.2‒98.0) positive predictive value 81.5 (88.4‒97.5) 73.9 (51.3‒88.9) negative predictive value 94.4 (88.4‒97.5) 90.7 (84.0‒94.9) positive likelihood ratio 18.7 (7.7‒45.1) 12.0 (5.2‒27.8) negative likelihood ratio 0.25 (0.13‒0.48) 0.1 (0.06‒0.18) pulmonary contusion sensitivity 68.8 (53.6‒80.9) 43.8 (29.8‒58.7) specificity 92.3 (84.9‒96.4) 73.1 (63.3‒81.1) positive predictive value 80.5 (64.6‒90.6) 42.8 (29.1‒57.7) negative predictive value 86.5 (78.4‒92.0) 73.7 (64.0‒81.7) positive likelihood ratio 8.9 (4.5‒17.7) 1.6 (1.0‒2.55) negative likelihood ratio 0.34 (0.2‒0.52) 0.77(0.6‒0.99) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com vafaei et al 32 and could, concentrate on areas with higher odds of injuries to some extent. however, in the hyacinthe et al. study a blinded specialist carried out ultrasonography, which might be the reason for the higher sensitivity rate in the present study. wilkerson and stone meta-analysis reported a sensitivity of 85‒100% for ultrasonography in diagnosis of thoracic cavity injuries (10). other studies, have also reported similar findings (23, 24). the differences might be attributed to inclusion and exclusion criteria of the studies. those studies have excluded patients with subcutaneous emphysema and intubated patients. subcutaneous emphysema interferes with examination of the parietal pleura using ultrasonography, making it difficult to identify hemothorax or pneumothorax in these areas. on the other hand, in the present study there was about 1‒2-hour time interval between ultrasonography and ct scan examinations. during this time, the lesions might have extended to reach a size that could make diagnose them easier. an attempt was made in this study to evaluate the diagnostic accuracy of ultrasonography as an alternative to x-ray. comparison of the results of these two techniques with those of ct scan showed that ultrasonography is superior to chest x-ray in initial evaluations. however, ultrasonography alone has a lower diagnostic value. therefore, it is advisable to find ways to increase the efficacy and accuracy of the ultrasonography technique. one of these ways is to combine ultrasonography with other indexes used for the diagnosis of traumatic lesions (25). this needs to be studied further. conclusion: the results of the present study showed that ultrasonography is preferable to radiography in the initial evaluation of patients with traumatic injuries to the thoracic cavity. however, the low sensitivity of the ultrasonography technique in comparison to ct scan, its reliance on operator skill, and some other limitations have made it only an initial test, necessitating confirmation using other techniques. acknowledgments: we are pleased to acknowledge from all staff of imam hossein hospital for their contribution in the present study. conflict of interest: we declare that the authors of this article have no competing interests. funding support: none. authors’ contributions: all authors met four criteria for authorship contribution based on recommendations of the 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department of neurology, faculty of medicine, al-azhar university, cairo, 11651, egypt. 2. department of neurology, al-araby international hospital, monufia, 32951, egypt. 3. department of internal medicine, faculty of medicine, al-azhar university, cairo, 11651, egypt. 4. department of pediatrics, faculty of medicine, tanta university, 31511, egypt. 5. department of neurology, shebin elkom teaching hospital, monufia, 32951, egypt. 6. egyptian intensive care fellowship, shebin elkom teaching hospital, monufia, 32951, egypt. received: july 2022; accepted: august 2022; published online: 13 september 2022 abstract: porphyria is a challenging metabolic disease due to its heterogeneous presentation symptoms and its difficult diagnosis. many affected individuals can complain of recurrent neuro-visceral attacks per year, some of which may be persistent and life-threatening, which is confusing if there is no established diagnosis. although the motor manifestations, autonomic changes and seizure are highly suggestive, the diagnosis is often overlooked and needs confirmatory genetic testing. to the best of our knowledge, the acute intermittent porphyria (aip) reported in this case, involving severe electrolyte disturbances and rapid severe weakness is a challenging neurometabolic case and is extremely rare worldwide. here, we reported a case of aip in a young girl who presented to the emergency department of al-araby international hospital, monufia, egypt with severe abdominal pain, constipation, and headache which had started 10 days ago. it seems that the diagnosis of porphyria should be considered particularly in those patients with abdominal complaints associated with electrolyte disturbances, seizures, and severe progressive neuropathy. keywords: electrolyte imbalance; porphyria, acute intermittent; polyneuropathies cite this article as: abed e, saeed mo, el-hamid ba, elsayed am, dawoud h, heikal nm, et al. acute intermittent porphyria as a rare challenging neuro-metabolic disease; a case report. arch acad emerg med. 2022; 10(1): e74. https://doi.org/10.22037/aaem.v10i1.1780. 1. introduction porphyrias are a group of rare metabolic disorders presenting a wide range of clinical manifestations. as a result of the genetic mutation in the enzymatic pathway involved in heme biosynthesis, a specific subtype of acute porphyrias can arise (1). the acute porphyrias can be either autosomal dominant, such as acute intermittent porphyria (aip), variegate porphyria, and hereditary coproporphyria, or autosomal recessive, such as delta-aminolevulinic acid (ala) dehydratase ∗corresponding author: elsayed abed; department of neurology, faculty of medicine, al-azhar university, cairo, 11651, egypt. email: elsayedabed.226@azhar.edu.eg, tel: 00201062635615, orcid: https://orcid.org/00000001-6494-3874. deficiency. enzymatic defect in the porphobilinogen deaminase (pbgd) can cause aip; a rare autosomal dominant disease that can be easily confused with other diseases (2). clinical presentation of aip is rare before puberty and the diagnosis is suggested by a triad of symptoms; severe abdominal pain, quadriparesis due to peripheral nerve involvement, delirium, and depression as the most common neuropsychiatric manifestation, which dominates the clinical picture. despite the rarity of the disease, the diagnosis may be confirmed by a decreasing level of porphobilinogen in the erythrocytes. however, although the autonomic changes and seizure are highly suggestive, the diagnosis is often overlooked and needs confirmatory genetic testing (3). moreover, early diagnosis may considerably improve patients’ prognosis through proper management. here we reported a case of aip presenting to emergency department with severe electhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. abed et al. 2 table 1: the laboratory findings as well as cerebrospinal fluid and genetic analyses of the patient variable value complete blood count red blood cells (cells/mcl) 4 million white blood cells (cells/mcl) 55000 platelets count (/mcl) 226,000 hemoglobin (gm/dl) 13 venus blood gas analysis ph 7.31 pco2 (mm hg) 42 po2(mm hg) 40 electrolyte sodium (meq/l) 108 potassium (meq/l) 2.7 total calcium (mg/dl) 4.9 ionized calcium (mg/dl) 3.5 magnesium (meq/l) 0.7 phosphorus (meq/l) 2.1 osmolality urine osmolality (moml/kg) 277 serum osmolality (moml/kg) 252 serum chloride (meq/l) 73 urinary calcium/creatinine ratio 1.053 csf analysis csf appearance clear, colorless csf protein (mg/100 ml) 35 csf glucose (mmol/l) 4.2 csf chloride (mmol/l) 125 csf lactate (mmol/l) 2.1 csf culture and sensitivity negativ gene analysis hbms gene nm_000190.3:c.76c>t csf: cerebrospinal fluid. trolyte disturbances and rapid severe weakness. it seems that, the diagnosis of aip should be considered when patients present with severe electrolyte imbalance and progressive neuropathy. 2. case presentation a 13-year-old girl with no history of medical or familial diseases presented to the emergency department of al-araby international hospital, monufia, egypt with severe abdominal pain, constipation, and headache, which had started 10 days ago. within the next few days following admission, the patient developed an attack of generalized tonic-clonic seizure associated with low-grade fever. on examination, the patient was confused in post ictal state. otherwise, the neurological and general examination was unremarkable. patient was hemodynamically stable. urgent brain computed tomography (ct) scan showed brain edema (figure 1). cerebrospinal fluid (csf) analysis, routine blood chemistry tests, blood culture, and serum electrolyte evaluation were performed. on a clinical basis, central nervous system infection was suspected and the patient started to receive acyclovir. due to severe abdominal pain, abdominopelvic ct scan with contrast was done, which revealed marked distention of large bowel, and no definite air-fluid level or obstructing masses (figure 1). the initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level: 108 milliequivalents per liter (meq/l), potassium level: 2.7 meq/l, total calcium level: 4.9 mg/dl, ionized calcium level: 3.5 mg/dl, magnesium level: 0.7 meq/l, and phosphorus level: 2.1 meq/l (table 1). within the next few days, the patient began to become agitated and developed generalized muscle pain despite proper correction of resistant hyponatremia with hypertonic saline 3%. in addition, the patient started to develop polyuria, and polydipsia, despite the normovolemic state, confirmed by clinical examination and central venous pressure monitoring. high suspicion to bartter-like syndrome was raised as the renal tubular defect with increased renal loss of electrolyte was confirmed by the following laboratory investigation: urine osmolarity 277moml/kg, serum osmolality 252 mmol/kg, serum chloride 73 meq/l, and urinary calcium/creatinine ratio 1.053 (table 1). within the next few days, she developed weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic. the rest of the examination was normal. our opinion about the case changed and we had a rising concern about genetic disease. at that time, the whole-exome sequencing was sent abroad to centogene gmbh (rostock, germany) for genetic analysis. electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy (prolonged first time (f) wave latencies with reduced amplitude of compound motor action potentials). unfortunately, the condition worsened till the patient became intubated and mechanically ventilated due to respiratory muscle involvement. the csf examination showed cytoalbuminous dissociation, and this made the diagnosis more in favor of guillain-barre syndrome (gbs). the patient received intravenous immunoglobulin (iv ig) (2gm per kg divided over 5 days) with partial improvement. due to the failure of multiple trials for weaning from mechanical ventilation, tracheostomy was performed. genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase (hmbs) gene, which confirmed the diagnosis of autosomal dominant aip (figure 2). the patient received dextrose 25% and 2 doses of hemin 250 mg once daily for four days, 2 weeks apart followed by another dose after 2 months. there was a marked improvement regarding the weakness, and abdominal pain, and we managed to wean her from mechanical ventilation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e74 figure 1: left image: brain computed tomography scan without contrast showed grey-white matter differentiation of the cerebrum and cerebellum is preserved, however there is subtly reduced density of the cerebrum relative to the cerebellum, suggesting mild/early diffuse edema. no sulcal effacement and ventricles are normal in appearance. right and middle image: abdominal computed tomography scan with intravenous contrast reveals marked distension of stomach and duodenum. figure 2: summary of genetic testing findings (left) and its interpretation (right). 3. discussion porphyria is a challenging metabolic disease due to its heterogeneous presentation symptoms and its difficult diagnosis. it is a common term incorporating many inborn metabolic diseases affecting heme biosynthesis. for each of the eight enzymes included in this pathway, there is an associated known defect. due to these defects, an intermediate precursor is accumulated (1, 4). there are multiple classifications for porphyria but distinctly it is attributed to either the site of accumulation of the metabolite or the phenotypically dominant manifestations (5). the commonest type was aip (3). it occurs mainly due to an autosomal dominant enzymatic defect in the third cascade of the heme synthesis pathway. defects of the hmbs gene, which encodes pbgd enzyme, lead to the accumulation of porphyrin precursors such as ala and porphobilinogen. these toxic metabolites accumulate in the liver and become deposited in many systems causing problems with a wide range of severity and affecting different organs. renal failure and electrolyte imbalances are also among the possible emerging heterogeneous presentation sequelae. in the present report, we introduced a case of aip, in which a young girl presented with a rare presentation. due to the strong association between hormonal changes and precipitation of attacks, aip is more prevalent in females. our case showed severe weakness in both upper and lower limbs that progressed to involve the respiratory muscles due to severe peripheral neuropathy. this could be attributed to axonal dysfunction due to na+/k+ pump energy dysfunction resulting from the lack of heme availability and the direct neurotoxic effect of porphyrin precursors (6). severe resistant hyponatremia was observed in our case either due to primary salt wasting or the syndrome of inappropriate antidiuretic hormone secretion as reported in a previous study (7). the degree of axonal damage probably predicts the ultimate prognosis. however, some patients with the gbs variant remain permanently quadriparetic (8). once a porphyria attack is diagnosed, precipitating factors or provoking agents such as dietary changes with low caloric intake, certain drugs, stressful conditions, and infections should be avoided (4, 5). treatment for aip includes both supportive and specific therapies. in addition, glucose supplements or parenteral administration of hematin are suggested (8). clinical evaluation and parental targeted testing are recommended to establish whether the detected variant is inherited or de novo. although some attacks may be persistent and life-threatening, early diagnosis may considerably improve this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. abed et al. 4 patient prognosis through proper management. 4. conclusion porphyric neuropathy is a predominantly motor neuropathy with different clinical presentations that may mimic various neuropathies, such as gbs with diffuse axonal involvement, or lead neuropathy with specific nerve involvement, or bilateral radial neuropathy. a diagnosis of porphyria should be considered particularly in patients with abdominal complaints associated with electrolyte disturbances, seizures, and severe progressive neuropathy. moreover, early diagnosis may considerably improve patient prognosis through proper management. 5. declarations 5.1. acknowledgments the authors would like to express their gratitude to the department of neurology, faculty of medicine, al-azhar university, cairo, egypt. 5.2. authors’ contributions all authors participated in manuscript writing and editing. all authors have read and approved the manuscript. 5.3. funding and supports this study was self-funded by the authors. 5.4. competing interests the authors declare that they have no competing interests. 5.5. ethics approval and consent to participate this study was conducted in concordance with declaration of helsinki and the participant signed a written informed consent before the submission of the case report. the institutional review board (irb) approval was obtained from the ethical committee of faculty of medicine, al-azhar university, cairo, egypt. references 1. spiritos z, salvador s, mosquera d, wilder j. acute intermittent porphyria: current perspectives and case presentation. ther clin risk manag. 2019;15:1443-51. 2. ma y, teng q, zhang y, zhang s. acute intermittent porphyria: focus on possible mechanisms of acute and chronic manifestations. intractable rare dis res. 2020;9(4):187-95. 3. phillips jd. heme biosynthesis and the porphyrias. mol genet metab. 2019;128(3):164-77. 4. cardenas jl, guerrero c. acute intermittent porphyria: general aspects with focus on pain. curr med res opin. 2018;34(7):1309-15. 5. bustad hj, kallio jp, vorland m, fiorentino v, sandberg s, schmitt c, et al. acute intermittent porphyria: an overview of therapy developments and future perspectives focusing on stabilisation of hmbs and proteostasis regulators. int j mol sci. 2021;22(2):675. 6. alqwaifly m, bril v, dodig d. acute intermittent porphyria: a report of 3 cases with neuropathy. case rep neurol. 2019;11(1):32-6. 7. hift rj, meissner pn. an analysis of 112 acute porphyric attacks in cape town, south africa: evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity. medicine. 2005;84(1):48-60. 8. schutte c-m, van der meyden ch, van niekerk l, kakaza m, van coller r, ueckermann v, et al. severe porphyric neuropathy-importance of screening for porphyria in guillain-barre syndrome: clinical alert. s afr med j. 2016;106(1):44-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 47 emergency (2016); 4 (1): 47 letter to editor management of deep vein thrombosis in emergency departments; time to change the viewpoint gholamreza faridaalaee1, mohammad shafe shakori2* 1emergency medicine department, maragheh university of medical sciences, maragheh, iran. 2internal medicine department, urmia university of medical sciences, urmia, iran. *corresponding author: mohammad shafe shakori; internal medicine department, imam khomeini hospital, urmia university of medical sciences, urmia, iran. tel: +989111310448, fax: +984433457286, e-mail: shafe448@yahoo.com received: july 2015; accepted: august 2015 to the editor: lot formation within a deep vein is called deep vein thrombosis (dvt). it occurs in about 100 persons per 100,000 population each year in the united states and leads to about 600,000 pulmonary thromboembolism (pte) cases and also causes 60,000 deaths annually (1, 2). for many years, unfractionated heparin (ufh) and warfarin have been used for treatment of dvt and prevention of pte (3). this approach needs hospitalization and necessitates close monitoring by partial thromboplastin time (ptt) measurement (4). by development of low molecular weight heparin (lmwh) the need for laboratory monitoring was resolved. in addition, some investigators also claimed that it is accompanied with less bleeding risk and better outcome (5). accordingly, outpatient management of dvt became possible and nowadays american college of chest physicians (accp) advocates outpatient therapy for dvt. this method has been shown to be safe and effective in presence of home adequacy criteria (6). home adequacy is defined by accp as “well-maintained living conditions, strong support from family or friends, phone access, and ability to quickly return to the hospital if there is deterioration” (7). yet, many physicians in iran prefer to hospitalize all dvt patients because of their belief in the impossibility of outpatient treatment. in the current study, we evaluated outpatient therapy of 10 patients with lower extremity dvt in emergency department (ed) of imam khomeini hospital of urmia, iran from 21 july 2014 to 15th march 2015. dvt was confirmed by ultrasound in all 10 patients. none of them had previous history of dvt, pte, use of anticoagulant, allergy to heparin or warfarin, hemodynamic instability, home inadequacy, and comorbidity that mandate hospitalization. patients received first dose of subcutaneous lmwh (enoxaparin) and oral warfarin, and were discharged from ed on the same day. the home medical prescription included subcutaneous lmwh 1mg/kg twice daily, plus 5 mg oral warfarin daily. the dose of warfarin was adjusted based on international normalized ratio (inr). the goal inr was considered 2-2.5. bleeding, pte, recurrent dvt and mortality had not happened in 2, 4, 6, and 30 days follow-up after ed discharge. it seems that it is time to change our viewpoint in this regard. the importance of this matter is duplicated when we are confronted with overcrowding of emergency departments and loss of hospital beds following implementation of health sector evolution plan in iran. references: 1. mackman n, becker rc. dvt: a new era in anticoagulant therapy. arterioscler thromb vasc biol. 2010;30(3):369-71. 2. baratloo a, safari s, rouhipour a, et al. the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis. emergency. 2014;2(1):1-11. 3. ansell j, hirsh j, poller l, bussey h, jacobson a, hylek e. the pharmacology and management of the vitamin k antagonists: the seventh accp conference on antithrombotic and thrombolytic therapy. chest. 2004;126(3_suppl):204s-33s. 4. zidane m, schram mt, planken ew, et al. frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. arch intern med. 2000;160(15):2369-73. 5. erkens pm, prins mh. fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. cochrane database syst rev. 2010 (9):cd001100. 6. zidane m, van hulsteijn lh, brenninkmeijer bj, huisman mv. out of hospital treatment with subcutaneous low molecular weight heparin in patients with acute deep-vein thrombosis: a prospective study in daily practice. haematologica. 2006;91(8):1052-8. 7. kearon c, akl ea, comerota aj, et al. antithrombotic therapy for vte disease: antithrombotic therapy and prevention of thrombosis: american college of chest physicians evidencebased clinical practice guidelines. chest. 2012;141(2_suppl):e419s-e94s. c emergency. 2016; 4 (4): 207-210 br i e f re p o rt the reasons of renal transplant recipients’ admission to the emergency department; a case series study erdal uysal1∗, mehmet dokur2, hasan bakir1, mehmet ali ikidag3, turkay kirdak4, hatem kazimoglu5 1. department of general surgery, sanko university school of medicine, gaziantep, turkey. 2. department of emergency, sanko university school of medicine, gaziantep, turkey. 3. department of radiology, sanko university hospital, gaziantep, turkey. 4. department of general surgery, uludag universtiy school of medicine, bursa, turkey. 5. department of urology, sanko university school of medicine, gaziantep, turkey. received: december 2015; accepted: february 2016 abstract: introduction: renal transplantation are admitted to emergency department (ed) more than normal population. the present brief report aimed to determine the reasons of renal transplant patient’s ed visits. methods: this retrospective case series study analyzed the reasons of renal transplant recipients admission to one ed between 2011 and 2014. the patient data were collected via a checklist and presented using descriptive statistics tools. results: 41 patients with the mean age of 40.63 ± 10.95 years were studied (60.9% male). the most common ed presenting complaints were fever (36.6%) and abdominal pain (26.8%). infections were the most common final diagnosis (68.3%). among non-infectious causes, the most common was acute renal failure (9.7%). 73.2% of the patients were hospitalized and no cases of graft loss and mortality were seen. conclusion: the most common reason for ed admission was fever, and infections were the most common diagnosis. acute gastroenteritis being the most frequent infection and among non-infectious problems, acute renal failure was the most frequent one. keywords: kidney transplantation; patient readmission; emergency service, hospital; epidemiologic studies © copyright (2016) shahid beheshti university of medical sciences cite this article as: uysal e, dokur m, bakir h, ikidag ma, kirdak t, kazimoglu h. the reasons of renal transplant recipients admission to the emergency department; a case series study. emergency. 2016; 4 (4): 207-210. 1. introduction since the introduction of highly effective immunosuppressive agents, organ transplant patients survive significantly longer and the number of patients with successful kidney transplantation is increasing worldwide. however, immunosuppressive therapies raise other distinct health problems that necessitate such patients visiting emergency departments (ed) with a variety of presentations. they are admitted to eds more frequently and with more complex issues (1). lack of sufficient knowledge and experience of approach to renal transplant recipients in ed poses a major problem in management of these patients (2). emergency physicians ∗corresponding author: erdal uysal; sanko university school of medicine, department of general surgery incilipinar mah ali fuat cebesoy bulv. no: 45 27090, sehitkamil gaziantep, turkey. phone: 00903422115000, fax: 0090 3422115010 email:drerdaluysal@hotmail.com should be familiarized with major complications and ways to manage the emergent problems of the mentioned patients (2). they may admit to ed for issues either related or not related to renal transplantation including acute rejection episodes, infections, cardiovascular diseases, side effects of immunosuppressive drugs, and the problems of renal transplant surgery (1-3). it is important to distinguish transplantation related issues due to their vital importance in protection of graft. surprisingly, there are very few studies on the subject, most of which emphasize the importance of infections in renal, liver and heart/lung transplant recipients (2, 4, 5). in a study, the causes of renal transplant patients death were found to be infections with 69.6%, cardiovascular diseases with 12.7% and acute rejection with 6.9%, respectively (6). based on the above-mentioned, the aim of the present brief report is to determine the reasons of renal transplant patient’s ed visits and highlight the importance of preparedness for dealing with them. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. uysal et al. 208 2. methods this retrospective case series study analyzed the reasons of renal transplant recipient’s admission to the ed of sanko university hospital, gaziantep, turkey. 41 patients, who underwent renal transplantation between 2011 and 2014 were enrolled. the patient data were collected from clinical files and electronic medical records via filling out the initially prepared checklist including demographic characteristics (age, sex), ed presenting complaints, number of ed admissions, donor type, consulting services, as well as patient disposition and final diagnosis and outcome (mortality, graft loss). the data were entered to a pre-designed database and analyzed with spss 13.0 statistical software. data are presented as mean ± standard deviation or frequency and percentage. the researchers adhered to the principles of helsinki declaration and research ethics and kept patient information confidential. 3. results 160 renal transplants were performed during the study period in the studied center. among which, 41(26%) patients with the mean age of 40.63 ± 10.95 years visited the ed at least once (60.9% male). the range of time interval between renal transplantation to ed admission was 1-36 months. the mean duration of ed stay was 2.1 ± 0.69 (1.2 3.4) hours. table 1 presents the characteristics of studied patients. the most common ed presenting complaint was fever, followed by abdominal pain, nausea and vomiting. table 2 summarizes the final diagnosis of studied patients based on infectious and non-infectious causes. infections were the most common final diagnosis (28 (68.3%) patients) and the most common infection was acute gastroenteritis detected in 11 (26.8%) patients. among non-infectious causes, the most common was acute renal failure observed in 4 (9.7%) patients. the mean time interval between ed presentation and disposition was 1.9 ± 0.46 (1.1 2.3) hours and 73.2% (30) of the patients were hospitalized. no cases of graft loss and mortality were seen. 4. discussion in this retrospective case series, 26% of renal transplant recipients of the hospital visited the ed during 3 years. the most common reason for ed admission was fever, and infections were the most common diagnosis. acute gastroenteritis being the most frequent infection and among non-infectious problems, acute renal failure was the most frequent one. infections are among the usual complications of immunosuppressive therapy (7). previous studies table 1: characteristics of studied patients characteristics number (%) gender male 25 (61.0) female 16 (39.0) number of ed admissions 1 22 (53.7) 2 11 (26.8) 3 8 (19.5) disposition discharge from ed 11 (26.8) hospitalization 30 (73.2) donor type cadaveric 21 (51.2) living 20 (48.8) ed presenting complaint fever 15 (36.6) abdominal pain 11 (26.8) nausea and vomiting 9 (21.9) diarrhea 6 (14.6) headache 4 (9.8) dyspnea 3 (7.3) hematuria and dysuria 3 (7.3) low back pain 2 (4.9) extremity pain 2 (4.9) palpitation 1 (2.4) hypertension 1 (2.4) consultation nephrology 29 (70.7) infectious diseases 13 (31.7) transplant surgeon 6 (14.6) orthopedics 2 (4.9) cardiology 1 (2.4) ed: emergency department. table 2: final diagnosis of studied patients diagnosis number (%) infectious acute gastroenteritis 11 (26.8) upper respiratory tract infection 9 (21.9) urinary tract infection 4 (9.7) pneumonia 2 (4.8 ) herpes infection 1 (2.4) soft tissue infection ∗ 1 (2.4) non-infectious acute renal failure 4 ( 9.7) acute graft rejection 3 (7.3) acute cholecystitis∗ 2 (4.8) wrist fractures∗ 2 (4.8) cardiovascular disease ∗ 1 (2.4) anxiety ∗ 1 (2.4) * unrelated to transplantation. have declared infection as the most frequent cause of renal transplant patient’s ed visits (2, 3). the most common post-renal transplantation sources of infections are reported to be urinary tract, followed by muco-cutaneous and upper respiratory tract (2, 3, 8-10). however, in the present case this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 209 emergency. 2016; 4 (4): 209-210 series gastroenteritis was the most frequent infection and about twice tokalak et al. study (2). this may be due to dietary habits of our patients or quality of food and water they used. however, neither sepsis nor graft loss was developed in any of these patients. pneumonia was diagnosed in two patients, pneumococcal in one case and atypical in the other. acute renal failure is a major risk factor of rejection among renal transplant recipients (11). in our study, 4 patients were diagnosed with acute renal failure, 2 of them were diagnosed with acute graft rejection and the other two with immunosuppressive drug toxicity. acute graft rejections were successfully treated and the patient’s blood urea nitrogen and creatinine values reversed to normal and for the two intoxicated patients, immunosuppressive dose adjustment was made. no case of graft loss and mortality was seen. one of the most important causes of mortality in renal transplant patients is cardiovascular diseases (2)(12). the risk of cardiovascular disease in patients with renal transplantation has been reported to be 5 times higher than normal population (1). in this study, one patient presented with chest pain and palpitations, which was diagnosed as supraventricular tachycardia and treated in the coronary intensive care unit. hospitalization rate of 73.1% in the present case series was high compared to previous studies (2, 13). the reason was the preference of studied center clinicians for inpatient management of renal transplant patients. this study has methodological restrictions, as it is a retrospective case-series with low sample size. in addition, some of the renal transplant patients of the hospital might have been admitted to the eds of other hospitals and were missed. despite the mentioned limitations, the findings of this study could be helpful in raising awareness regarding renal transplant complications among emergency physicians. 5. conclusion the most common reason for ed admission was fever, and infections were the most common diagnosis. acute gastroenteritis being the most frequent infection and among non-infectious problems, acute renal failure was the most frequent one. 6. appendix 6.1. acknowledgements the authors would like to thank prof. dr. m. fatih yuzbasioglu for assisting in preparation of the manuscript. 6.2. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. conflict of interest none 6.4. funding/ support none references 1. venkat kk, venkat a. care of the renal transplant recipient in the emergency department. annals of emergency medicine. 2004;44(4):330-41. 2. tokalak i, basaran o, emiroglu r, karakayali h, bilgin n, haberal m. problems in postoperative renal transplant recipients who present to the emergency unit: experience at one center. transplantation proceedings. 2004;36(1):184-6. 3. kartal m ge, eray o, gungor f. factors affecting to hospital admission for renal transplant patients in the emergency department. turkish journal of emergency medicine. 2009;9(4):159-62. 4. sternbach gl, varon j, hunt sa. emergency department presentation and care of heart and heart/lung transplant recipients. annals of emergency medicine. 1992;21(9):1140-4. 5. savitsky ea, votey sr, mebust dp, schwartz e, uner ab, mccain s. a descriptive analysis of 290 liver transplant patient visits to an emergency department. academic emergency medicine : official journal of the society for academic emergency medicine. 2000;7(8):898-905. 6. reis ma, costa rs, ferraz as. causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991. journal of the royal society of medicine. 1995;88(1):24-7. 7. fishman ja, rubin rh. infection in organ-transplant recipients. the new england journal of medicine. 1998;338(24):1741-51. 8. becker s, witzke o, rubben h, kribben a. [urinary tract infections after kidney transplantation: essen algorithm for calculated antibiotic treatment]. der urologe ausg a. 2011;50(1):53-6. 9. trzeciak s, sharer r, piper d, chan t, kessler c, dellinger rp, et al. infections and severe sepsis in solid-organ transplant patients admitted from a university-based ed. the american journal of emergency medicine. 2004;22(7):530-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. uysal et al. 210 10. schmaldienst s, dittrich e, horl wh. urinary tract infections after renal transplantation. current opinion in urology. 2002;12(2):125-30. 11. koo eh, jang hr, lee je, park jb, kim sj, kim dj, et al. the impact of early and late acute rejection on graft survival in renal transplantation. kidney research and clinical practice. 2015;34(3):160-4. 12. rigatto c. clinical epidemiology of cardiac disease in renal transplant recipients. seminars in dialysis. 2003;16(2):106-10. 13. kim hc, park sb. infection in the renal transplant recipient. transplantation proceedings. 2000;32(7):1974-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 48 emergency (2014); 2 (1): 48-49 case report epidural hematoma following hemodialysis in a methanol poisoned patient; a case report payman moharamzadeh1, farzad rahmani1*, mahboob pouraghaei1, hanieh ebrahimi bakhtavar2, ehsan mohammadzadeh abachi3 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. department of emergency medicine, ardabil university of medical sciences, ardabil, iran 3. faculty of medicine, tabriz university of medical sciences, tabriz, iran abstract brain injury associated with methanol toxicity can be ischemic, necrotic or hemorrhagic in nature. it most commonly affects the putamen area bilaterally; however, it can be seen in other locations. this report describes a 22year-old intoxicated patient who developed an epidural hematoma following hemodialysis. heparinization during hemodialysis may contribute to cerebral hemorrhagic complications in methanol poisoning. in addition, a history of head trauma may raise the incidence of post-hemodialysis hemorrhagic brain insults. heparin-free dialysis or peritoneal dialysis can be a good option in these cases. key words: hemodialysis; epidural hematoma; methanol; alcoholic intoxication cite this article as: moharamzadeh p, rahmani f, pouraghaei m, ebrahimi bakhtavar h, moharramzadeh abachi h. epidural hematoma following hemodialysis in a methanol poisoned patient; a case report. emergency. 2014;2(1):48-9. introduction:1 rain injury associated with methanol toxicity can be ischemic, necrotic or hemorrhagic in nature. it most commonly affects the putamen area bilaterally; however, it can be seen in other locations. the exact mechanism of these pathologies remains unknown. possible hypotheses include a direct toxic effect of methanol or its metabolites, injury secondary to anoxia and acidosis and, more recently proposed, cerebral vasospasm induced by a large rise in intracellular calcium (1, 2). this report describes an intoxicated patient who developed an epidural hematoma and loss of consciousness following hemodialysis. case report: a 22-year-old man presented to the emergency department (ed) with a history of tonic-clonic generalized seizures, loss of consciousness, and head trauma following consumption of 800 mg tramadol. on admission the patient's vital signs were as follows: systolic blood pressure = 160 mm hg, diastolic blood pressure = 80 mm hg, o2 saturation = 85%, pulse rate = 106/min, respiratory rate = 24/min and axillary temperature = 37.4°c. initial examination revealed agitation and bilateral pupil mydriasis with positive pupillary response to light. arterial blood gas (abg) analysis showed a high anion gap metabolic acidosis: ph = 6.80, paco2 = 30.4 mm hg, hco3 = 4.6 meq/l, na = 139 meq/l, cl = 108 meq/l. the metabolic acidosis in this patient could not be explained solely by lactic acidosis following seizure *corresponding author: farzad rahmani, emergency department, imam reza hospital, golgasht avenue, tabriz, iran. postal code: 5166614756. phone/fax: 00984113352078. email: farzadrhn88@gmail.com. received: 08 january 2014; accepted: 03 february 2014 activity so other potential causes were explored. a thorough history of the patient’s family revealed that the patient drank homemade alcohol three days prior to presentation. methanol poisoning was diagnosed on the basis of the previously mentioned history and initial evaluation and the decision was made to begin hemodialysis. due to the history of head trauma, a computed tomography scan (ct scan) of the brain was performed prior to sending the patient to the dialysis unit (figure 1). protective measures including ethanol gavage, folic acid, and sodium bicarbonate were administered to the patient while waiting to begin hemodialysis. hemodialysis was then performed for four hours. following hemodialysis, the patient’s acidosis was reduced, and the clinical features were improved. approximately one hour later, the patient’s level of consciousness decreased and unilateral mydriasis with negative pupillary light response (anisocoria) developed in the right eye. the patient was immediately intubated and brain ct scan was repeated (figure 2). a large epidural hematoma was seen in the right fronto-parietal lobe with evidence of mass effect. the patient was taken to the operating room for hematoma evacuation. discussion: substance abuse is currently a worldwide problem. tramadol and homemade alcohols are among the most commonly abused substances and each can result in several harmful consequences. brain injury in methanol toxicity can be ischemic, necrotic or hemorrhagic in nature. the exact mechanism of these pathologies remains unknown. extracorporeal removal plays a fundamental role in the management of methanol poisoning, though specific techniques and indications are not b this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com moharamzadeh et al 49 yet determined. conventional hemodialysis is typically the best method to rapidly remove both alcohol and its toxic metabolites because of its widespread availability and known efficacy (3, 4). peritoneal dialysis and other forms of continuous renal replacement therapy are inefficient and are not recommended except in specific rare situations such as cerebral hemorrhagic complications following regular hemodialysis (3, 5). systemic heparinization during hemodialysis may contribute to the hemorrhage observed in the necrotic areas of the brain in these poisoned patients. awareness of the potential complications of hemodialysis may assist in their prevention (6). there are numerous reports about both the different types of cerebral hemorrhagic insults in methanol poisoning and following hemodialysis, but reports of epidural hematoma (edh) are rare (7). most edhs are caused by direct impact injuries to the skull (8). while it is unlikely that a false negative primary interpretation of a brain ct scan in a crowded emergency department may contribute to the occurrence of edh secondary to hemodialysis, it is possible (9). a review of the published literature reveals that heparinization during hemodialysis may contribute to cerebral hemorrhagic complications in methanol poisoning (10, 11). considering a positive history of head trauma even with a normal brain ct scan may also raise the incidence of this complication, though further research is needed. heparin-free dialysis or peritoneal dialysis may be a good option in these cases. figure 1: brain ct scan of patient before hemodialysis.  figure 2: brain ct scan of patient after hemodialysis.  acknowledgments: we acknowledge the entire staff of the emergency department and dialysis unit of imam reza hospital, tabriz, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. references: 1. blanco m, casado r, vazquez f, pumar j. ct and mr imaging findings in methanol intoxication. am j neuroradiol. 2006;27(2):452-4. 2. feany mb, anthony dc, frosch mp, zane w, de girolami u. august 2000: two cases with necrosis and hemorrhage in the putamen and white matter. brain pathol. 2001;11(1):121-5. 3. bayliss g. dialysis in the poisoned patient. hemodial int. 2010;14(2):158-67. 4. goodman jw, goldfarb ds. the role of continuous renal replacement therapy in the treatment of poisoning. sem dial. 2006;19(5):402-7. 5. kan g, jenkins i, rangan g, woodroffe a, rhodes h, joyce d. continuous haemodiafiltration compared with intermittent haemodialysis in the treatment of methanol poisoning. nephrol dial transpl. 2003;18(12):2665-7. 6. askar a, al-suwaida a. methanol intoxication with brain hemorrhage: catastrophic outcome of late presentation. saudi j kidney dis transpl. 2007;18(1):117-9. 7. taheri ms, noori m, shakiba m, jalali ah. brain ct-scan findings in unconscious patients after poisoning. int j biomed sci. 2011;7(1):1-5. 8. taussky p, widmer hr, takala j, fandino j. outcome after acute traumatic subdural and epidural haematoma in switzerland: a single-centre experience. swiss med wkly. 2008;138(19-20):281-5. 9. dolatabadi aa, baratloo a, rouhipour a, et al. interpretation of computed tomography of the head: emergency physicians versus radiologists. trauma mon. 2013;18(2):86-9. 10. phang p, passerini l, mielke b, berendt r, king eg. brain hemorrhage associated with methanol poisoning. crit care med. 1988;16(2):137-40. 11. janssen m, van der meulen j. the bleeding risk in chronic haemodialysis: preventive strategies in high-risk patients. neth j med. 1996;48(5):198-207. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 3 emergency (2015); 3 (1): 3-7 review article ebola hemorrhagic fever as a public health emergency of international concern; a review article saeed safari1, alireza baratloo1*, alaleh rouhipour2, parisa ghelichkhani3, mahmood yousefifard4 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of pediatrics, valeeasr hospital, ghazvin university of medical sciences, abyek, iran. 3. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. *corresponding author: alireza baratloo; department of emergency medicine, shohadaye tajrish hospital, tehran, iran. postal code: 1989934148; tel: +989122884364; fax: +982122721155; email: alirezabaratloo@yahoo.com received: 18 sep 2014; accepted: 10 nov 2014 abstract ebola hemorrhagic fever (ehf) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in yambuku (near the ebola river), democratic republic of congo, and in nzara, sudan. the current outbreak of the ebola virus was started by reporting the first case in march 2014 in the forest regions of southeastern guinea. due to infection rates raising over 13,000% within a 6-month period, ebola is now considered as a global public health emergency and on august 8th, 2014 the world health organization (who) declared the epidemic to be a public health emergency of international concern. with more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous ebola virus outbreak in the world. based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of ebola virus disease. key words: hemorrhagic fever, ebola; health; emergency responders; virology; infection control cite this article as: safari s, baratloo a, rouhipour a, ghelichkhani p, yousefifard m. ebola hemorrhagic fever as a public health emergency of international concern; a review article. emergency. 2015;3(1):3-7. introduction: bola hemorrhagic fever (ehf) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in yambuku (near the ebola river), democratic republic of congo, and also in nzara, sudan. there have been almost 20 other outbreaks that involve nearly 2500 cases happened before 2014. with the exception of a single case identified in the republic of ivory coast in the 1990s, all of them were reported in sub-saharan africa involving the sudan, gabon, uganda, and democratic republic of congo (1). but the current outbreak (2014), which is the largest one ever documented, is the first recorded outbreak of ebola in west africa (2). the previous largest outbreaks of ebola virus was identified in uganda in 2000–2001, which was caused by sudan ebola virus (sudv) subtype. this outbreak resulted in nearly 400 cases, 216 of which were laboratory confirmed and had 53% overall case-fatality rate (3). the 25th known outbreak of the ebola virus was started by reporting the first case in march 2014 in the forest regions of southeastern guinea. its infection rates reached 13,000% within a 6-month period. in august 8, 2014 the world health organization (who) declared the epidemic to be a public health emergency of international concern (2, 4). thereafter, ebola virus has spread through the west africa and appeared in senegal, sierra leone, liberia, nigeria, and now it has been reported in spain and united states of america, too. with more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous ebola virus outbreak all around the world (5). based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of ebola virus disease. virologic characteristics ebola virus is a lipid-enveloped ribonucleic acid (rna) virus, which belongs to the flavivirus family and known since 1976. it consists of five different sub-types and ebola virus zaire sub-type (zebov) was the first one to be recognized in the democratic republic of congo. the current ebola virus has 97% homology with zebov (6, 7). other subtypes include bundibugyo (bdbv), sudv, côte d'ivoire or tai forest (tafv) and reston ebola viruses (restv). ebola hemorrhagic fever (ehf), caused by zebov, has the highest fatality (57%–90%), followed e http://www.ncbi.nlm.nih.gov/mesh/68019142 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (1): 3-7 4 by sudv (41%–65%) and bdbv (40%) and these 3 subtypes are responsible for the large outbreaks that recently occurred in africa. however to date, restv infection has been observed in animals in asia and as an asymptomatic disease in humans, while tafv has only been identified in 2 human cases, both of which were nonfatal (4, 8, 9). transmission some authors claimed that a 44-year-old man suffering from malaria was the first identified fatal case of ehf who was infected using a contaminated needle for administration of parenteral chloroquine in the democratic republic of congo (previously named zaire) in 1976 (1). on the other hand, some researches indicated that the first person became infected through contact with an infected animal (4). fruit bats that live in guinea and its neighboring countries are considered as the natural hosts of ebola viruses, and other mammals serve as accidental hosts. this virus has been implicated as one of the major causes of decreasing african chimpanzee and gorilla populations in recent decades (1, 10, 11). ebola is one of the zoonotic viruses that can lead to a highly fatal disease in human beings. humans are also one of the accidental hosts and can be infected through close contact with blood and bodily fluids of another infected case (including humans and animals), either by direct contact or indirectly from a contaminated environment. it seems that mosquitoes and other insects do not play a role in virus transmission and also it is not spread through the air (1, 4, 10). ebola virus has high transmissibility and virulence and less than 10 viral particles are enough for becoming infected. the incubation period range is 2-21 days (average 5-6). fortunately, the disease is not transmissible until the patient becomes symptomatic, but it continues to be contagious, even postmortem (2, 12). family and healthcare providers caring for ebola patients are at the highest risk for becoming infected because of their possible contact with contaminated blood or body fluids. so the virus can easily spread if reasonable preventive precautions are not taken (4). clinical manifestation the patients with suggestive symptoms, including unexplained hemorrhage and risk factors within the last 3 weeks such as contact with suspected or confirmed ehf cases, or travel to an endemic area should be evaluated for ehf (2). ehf is a fatal disease (mortality rate 50%70%) that can occur 2-21 days after exposure to the virus. the initial clinical presentation is non-specific. early clinical symptoms of ehf include abrupt onset of fever, fatigue, myalgia and headache followed by progressive gastrointestinal symptoms such as anorexia, nausea, and abdominal discomfort accompanied by vomiting and diarrhea within 1-2 days. this process can lead to intravascular volume depletion and also profound electrolyte disorders, hypoperfusion, shock, and multi-organ failure (acute respiratory, liver, and renal failure) within a few days. the “hemorrhage” in the phrase “ebola hemorrhagic fever” is a late manifestation, which usually occurs as gastrointestinal bleeding, conjunctival hemorrhage, epistaxis, and hemorrhagic rash. some others believe that these symptoms occur only in a minority of patients, that is why they use “ebola virus disease” instead (1, 2, 5, 9, 10, 12-16). complete blood count usually shows leucopenia and thrombocytopenia, but hemoglobin levels almost never decrease significantly. intravascular volume depletion and hypoperfusion are manifested by metabolic lactic acidosis and renal insufficiency. massive diarrhea associates with profound hypokalemia and hematogenous spread of virus to the liver and spleen and leads to hepatocellular injury marked by elevated liver enzymes (2, 5, 12-14). analysis of coagulation profile shows increased prothrombin and partial thromboplastin times (pt and ptt) accompanied by detection of fibrin degradation products in the occurrence of disseminated intravascular coagulation (dic) (6). diagnosis apart from ebola virus, there are other types of viruses that can cause hemorrhagic fever, including crimeancongo hemorrhagic fever virus, marburg virus, lassa virus, and emerging ones such as lujo virus. these viruses have particular public health importance because of their spreading ability to healthcare workers, difficulties in their rapid recognition, lack of effective specific therapeutics, and high fatality rate (10). definite diagnosis of a clinically suspected case of ebola virus infection requires laboratory confirmation. in ehf, viremia develops after the fever and takes up to 3 days to confirm the diagnosis by proper laboratory evaluation. it is necessary to collect serum, plasma, or whole blood samples of at least 4 milliliters, and take them to the appropriate health department, refrigerated or on ice, for further testing. early diagnosis is confirmed via detecting viral antigens by using polymerase chain reaction (pcr) or enzyme-linked immunosorbent assay (elisa) on the blood sample. later in the disease course, antibodies against the virus such as immunoglobulin m (igm) and immunoglobulin g (igg) can also be detected. if the test results were positive, local and state health departments should be notified immediately. however, because of the extreme biohazard risk, using antigenor antibodybased assays or pcr testing should be performed in level 4 biosafety laboratories, which is more possible in developed countries where such laboratories are available (1, 2, 17). centers of disease control and prevention (cdc) have performed standardized enzyme-linked immunosorbent assay (elisa) for detection of ebola virus specific antibodies. this test has high sensitivity and can be used for detecting antibodies in human beings even 10 years after exposure to the virus (6). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 5 safari et al emergency (2014); 2 (3): ***-*** treatment there is no specific antiviral agent or vaccine against ebola viruses. therefore, supportive care is the most important aspect of its management. aggressive prevention of intravascular volume depletion is critical to avoid life-threatening complications by using proper fluid therapy, oxygen therapy, correcting profound electrolyte abnormalities, and preventing the complications of shock such as acid–base derangements. treatment of other infections, if they occur, and close monitoring of vital signs and regular biochemical and blood gas checks should be done. these proceedings are considered as the foundation of critical care medicine and should be applied to both resource-rich and resource-constrained settings. with improving supportive cares, ehf outcomes may also improve. symptom control with taking narcotics and benzodiazepines were often reported as the end-of-life therapy in some patients (2, 5, 14). a variety of chemotherapeutic agents have been tested for different stages of development. recombinant human activated protein c and recombinant nematode anticoagulant protein c2 are also among them. one drug identified as zmapp, has been used on several patients, however it remains unclear if it is effective or not. therefore, no food and drug administration (fda) approved agent exists against ebola (4, 6, 18-23). figure 1 shows the latest cdc algorithm regarding emergency department evaluation and management for possible ebola infected patients. prevention the current outbreak of ehf highlighted the importance of prevention strategies. health care workers have represented a considerable proportion of all infected cases. so educating and training the medical staff on universal precautions, risk assessment, and use of personal protective equipment is crucial. patients initially identified as having a possible viral hemorrhagic fever should be isolated until the results of their specific diagnosis are obtained from reference laboratories. it is important not to delay diagnosis and treatment of more common diseases, such as malaria or typhoid, during this period. follow-up of contact cases is essential for infection containment in case the patient tests are positive. specially equipped ambulances and trained staff should be prepared to do the transferring when needed (1, 10, 24). early diagnosis and rapid laboratory confirmation along with isolation of patients and following their contacts, as well as access to protective equipment and environmental decontamination are the mainstay of prevention. acknowledgments: we would like to thank centers of disease control and prevention (cdc) for investment of its algorithm regarding emergency department evaluation and management for possible ebola infected patients based on inquiry number: [ref:_00du0ycbu._500u0fpuod:ref]. conflict of interest: none funding support: none authors’ contributions: all authors met four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. laupland kb, valiquette l. ebola virus disease. can j infect dis med microbiol. 2014;25(3):128-9. 2. koenig kl, majestic c, burns mj. ebola virus disease: essential public health principles for clinicians. west j emerg med. 2014;[in press]. 3. okware s, omaswa f, zaramba s, et al. an outbreak of ebola in uganda. trop med int health. 2002;7(12):1068-75. 4. mccoy ce, lotfipour s, chakravarthy b, schultz c, barton e. emergency medical services public health implications and interim guidance for the ebola virus in the united states. west j emerg med. 2014; 15(7):723-7. 5. fowler ra, fletcher t, fischer wa, et al. caring for critically ill patients with ebola virus disease. perspectives from west africa. am j respir crit care med. 2014;190(7):733-7. 6. ansari aa. clinical features and pathobiology of ebolavirus infection. j autoimmun. 2014;55:1-9. 7. stahelin rv. membrane binding and bending in ebola vp40 assembly and egress. front microbiol. 2014;5:300. 8. macneil a, farnon ec, wamala j, et al. proportion of deaths and clinical features in bundibugyo ebola virus infection, uganda. emerg infect dis. 2010;16(12):1969-72. 9. roddy p, howard n, van kerkhove md, et al. clinical manifestations and case management of ebola haemorrhagic fever caused by a newly identified virus strain, bundibugyo, uganda, 2007–2008. plos one. 2012;7(12):e52986. 10. fletcher te, brooks tj, beeching nj. ebola and other viral haemorrhagic fevers. bmj. 2014;349:g5079. 11. leroy em, kumulungui b, pourrut x, et al. fruit bats as reservoirs of ebola virus. nature. 2005;438(7068):575-6. 12. fauci as. ebola—underscoring the global disparities in health care resources. n engl j med. 2014;371:1084-6. 13. bausch dg, towner js, dowell sf, et al. assessment of the risk of ebola virus transmission from bodily fluids and fomites. j infect dis. 2007;196(supplement 2):s142-s7. 14. feldmann h, geisbert tw. ebola haemorrhagic fever. the lancet. 2011;377(9768):849-62. 15. kortepeter mg, bausch dg, bray m. basic clinical and laboratory features of filoviral hemorrhagic fever. j infect dis. 2011;204(suppl 3):s810-s6. 16. paessler s, walker dh. pathogenesis of the viral hemorrhagic fevers. annu rev pathol. 2013;8:411-40. 17. saijo m, niikura m, ikegami t, kurane i, kurata t, morikawa s. laboratory diagnostic systems for ebola and marburg hemorrhagic fevers developed with recombinant proteins. clin vaccine immunol. 2006;13(4):444-51. 18. hensley le, stevens el, yan sb, et al. recombinant human activated protein c for the postexposure treatment of ebola hemorrhagic fever. j infect dis. 2007;196(supplement 2):s390s9. 19. geisbert tw, hensley le, jahrling pb, et al. treatment of ebola virus infection with a recombinant inhibitor of factor this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (1): 3-7 6 viia/tissue factor: a study in rhesus monkeys. the lancet. 2003;362(9400):1953-8. 20. choi jh, croyle ma. emerging targets and novel approaches to ebola virus prophylaxis and treatment. biodrugs. 2013;27(6):565-83. 21. warren tk, wells j, panchal rg, et al. protection against filovirus diseases by a novel broad-spectrum nucleoside analogue bcx4430. nature. 2014;508(7496):402-5. 22. elshabrawy ha, fan j, haddad cs, et al. identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and ebola, hendra, and nipah viruses by using a novel high-throughput screening assay. j virol. 2014;88(8):4353-65. 23. oestereich l, lüdtke a, wurr s, rieger t, muñoz-fontela c, günther s. successful treatment of advanced ebola virus infection with t-705 (favipiravir) in a small animal model. antiviral res. 2014;105:17-21. 24. woodrow cj, eziefula ac, agranoff d, et al. early risk assessment for viral haemorrhagic fever: experience at the hospital for tropical diseases, london, uk. j infect. 2007;54(1):6-11. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 7 safari et al emergency (2014); 2 (3): ***-*** figure 1: shows the latest cdc algorithm regarding emergency department evaluation and management for possible ebola infected patients. archives of academic emergency medicine. 2023; 11(1): e25 rev i ew art i c l e prognostic value of the leuko-glycemic index in acute myocardial infarction; a systematic review and metaanalysis roxana sadeghi1,2, shayan roshdi dizaji3, mohammadhossein vazirizadeh-mahabadi3, arash sarveazad4,5∗, seyed ali forouzannia3 † 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. physiology research center, iran university of medical sciences, tehran, iran. 4. colorectal research center, iran university of medical sciences, tehran, iran. 5. nursing care research center, iran university of medical sciences, tehran, iran. received: january 2023; accepted: february 2023; published online: 1 march 2023 abstract: introduction: in recent years, studies have provided evidence on the prognostic value of the leuko-glycemic index (lgi) in acute myocardial infarction (mi), but there is a lack of consensus. in addition, various reported cut-offs for lgi have raised concern regarding its clinical applicability. so, to conclude, through this systematic review and meta-analysis, we aimed to investigate all available evidence on the prognostic value of lgi in acute mi. methods: two independent researchers summarized records available in the four main databases of medline (via pubmed), embase, scopus, and web of science until 15 sep 2022. articles studying the prognostic value of the lgi in acute mi were included. finally, sensitivity, specificity, prognostic odds ratio, and the area under the curve (auc) for lgi were analyzed and reported. results: eleven articles were included (3701 patients, 72.1% male). based on the analyses, auc, sensitivity, and specificity for lgi in prediction of mortality following acute mi were 0.77 (95% ci: 0.73 to 0.80), 0.75 (95% ci: 0.62 to 0.84), and 0.66 (95% ci: 0.51 to 0.78), respectively. positive and negative post-test probability of lgi in prediction of mortality were 21% and 5%, respectively. auc, sensitivity, and specificity for lgi in prediction of major cardiac complications after acute mi were 0.81 (95% ci: 0.77 to 0.84), 0.84 (95% ci: 0.70 to 0.92), and 0.64 (95% ci: 0.49 to 0.84), respectively. also, the positive and negative post-test probability of lgi in this regard were 59% and 13%, respectively. conclusion: although the results demonstrated that the lgi could predict mortality and acute cardiac complication after mi, the low post-test probability of lgi in risk stratification of patients raises questions regarding its applicability. nevertheless, as most of the available studies have been conducted in the latino/hispanic population, further evidence is warranted to generalize the validity of this tool to other racial populations. keywords: glycemic index; prognosis; acute coronary syndrome; myocardial ischemia; death; myocardial infarction cite this article as: sadeghi r, roshdi dizaji s, vazirizadeh-mahabadi m, sarveazad a, forouzannia sa. prognostic value of the leukoglycemic index in acute myocardial infarction; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e25. https://doi.org/10.22037/aaem.v11i1.1915. ∗corresponding author: arash sarveazad, colorectal research center, rasool-e-akram hospital, nyayesh st., satarkhan st., tehran, iran. email: arashsarveazad@gmail.com, orcid: https://orcid.org/0000-0001-9273-1940. † corresponding author: seyed ali forouzannia, physiology research center, hemmat highway, p.o box: 14665-354, tehran, iran. email: s.ali.forouzannia@gmail.com, orcid: https://orcid.org/0000-0003-13717820. 1. introduction cardiovascular disease stands as the leading cause of death worldwide. the latest estimates in 2019 revealed an incidence of 523 million cardiovascular events, accounting for more than 18 million deaths and causing 32% of mortalities, globally. more than 75% of cardiovascular mortality is reported in middleand low-income countries, with myocardial infarction (mi) being the etiology in about half of cases (1, 2). identifying high-risk patients with poor prognoses suffering this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 2 from ischemic heart disease can assist physicians in providing the most appropriate care and implementing preventive measures (3, 4). utilizing blood biomarkers and decision tools has been demonstrated to be promising in the risk stratification of patients (5-10). the temporal profile of inflammatory markers released as the primary systemic response to ischemic heart disease can be helpful in diagnosing and estimating the severity of the ischemic injury. in this regard, multiple studies have revealed that increased concentration of specific inflammatory biomarkers is associated with the outcome of patients following acute mi (1113). however, low specificity, high cost, and unavailability of these biomarkers in some settings, hinder their clinical applicability. in 2010, quiroga castro et al. introduced the leuko-glycemic index (lgi) as a prognostic model for acute mi (14). synthesized through multiplying blood glucose level by leukocyte count, the lgi gained popularity for risk stratification of mi patients (15-17). the simplicity of calculation and routine measurement of involved variables on admission among mi patients made the leuko-glycemic index an accessible and easily interpretable test with no significant costs for patients and health systems. although, in recent years, studies have been conducted to validate the prognostic value of lgi among acute mi patients, there is still a lack of consensus (15-19). furthermore, the diversity of reported cut-offs among studies results in difficulty and uncertainty in the clinical use of this index. so, intending to determine the prognostic value of this index in acute mi patients, we ran a systematic review and meta-analysis of all available studies in the literature. 2. methods 2.1. study design the present systematic review and meta-analysis comprehensively explored all available studies on the prognostic value of the lgi among acute mi patients. based on the study aims, the pico has been defined as follows: p (population): patients with acute myocardial infarction i (intervention): the leuko-glycemic index c (comparison): comparison with the non-outcome group o (outcome): mortality and major cardiac complications the protocol of the current meta-analysis was registered in the online management systems of research project for shahid beheshti university of medical science. the local ethics committee approved the protocol of the current metaanalysis (ir.sbmu.retech.rec.1401.533). 2.2. search strategy in the beginning, relevant keywords were selected by experts in this field. emtree and mesh databases were extensively explored to find synonyms and other keywords. in addition, the title and abstract of related articles were screened to explore further keywords and synonyms. ultimately, using the acquired keywords, a comprehensive search in online databases of medline (via pubmed), embase, scopus, and web of science was conducted until sep 15, 2022. besides the systematic search, a manual search was performed on google, google scholar, and semantic scholar search engines for preprints and other probable records not found during the systematic search. we didn’t apply any language restrictions for selecting studies. the search queries of all explored databases are provided in supplementary material 1. 2.3. selection criteria inclusion criteria consisted of human studies on prognostic value of lgi in acute mi patients, published in peerreviewed journals, which calculated the leuko-glycemic index for risk stratification. studies on patients with other chief complaints rather than acute mi such as heart failure and covid-19, reporting data or patients undergoing surgical interventions such as coronary artery bypass graft (cabg) and other cardiac surgeries, studies without primary outcome measurements or existence of the outcomes at baseline were excluded. the other exclusion criteria were animal studies, duplicated studies, retracted or withdrawn studies, reviews, and case reports. 2.4. screening and data collection records collected through systematic and manual searches were exported to endnote software version 19.0 (clarivate analytics, philadelphia, pa, usa), and duplicates were removed. two independent reviewers screened the titles and abstracts of studies and retrieved the full texts of possibly related articles. then, based on the predefined inclusion and exclusion criteria, eligible articles were included in the present study. reviewer disagreements were addressed through discussion and consultations with a third expert. reporting data on study characteristics (first author name, publication and study year, country), type of study, sample size, age and gender distribution, reported outcomes, the timing of blood glucose and leukocyte measurements, reported cut-offs for the lgi, prognostic value indicators like sensitivity, specificity, and false and true positives and negatives (fp, tp, fn, tn) were extracted. before the study initiation, we considered collecting odds ratio (or), hazard ratio (hr), relative risk (rr), and the area under the curve (auc) of lgi in prognostication of acute mi in patients. however, we didn’t enter these values in our meta-analysis due to few studies reporting the above data and the inability to do pooled analysis on hr, or, and rr of included studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e25 table 1: characteristics of included articles study data study design language sample size mean age male (n) timing of lgi (hrs) patients setting outcome cut off of lgi tp tn fp fn cuestamero, 2021, ecuador 2015 to 2016 pcs spanish 205 62.99± 12.2 142 24 stand non-stelevated mi in-hospital mortality 851.6 23 116 65 1 in-hospital mcc (cardiac arrest, hf, cardiogenic shock, severe dysrhythmia, re-mi, ventricular thrombus, angina) 656.8 117 42 17 6 stand non-stelevated mi (all patients) 30-day mortality 1443 16 19 2 3 diaz benitez, 2016, cuba 2012 to 2013 cross spanish 142 68.2± 10.3 83 24 stand non-stelevated mi (nondiabetic patients) 30-day mcc 1443 28 56 17 1 stand non-stelevated mi (diabetic patients) 30-day mcc 1443 16 19 2 3 in-hospital mortality 738 23 53 329 0 in-hospital mortality 975 17 184 198 6 hirschson prado, 2014, argentina 2011 pcs english 405 61±12 348 8 st-elevated mi in-hospital mortality 1401 13 301 81 10 in-hospital mcc (cardiac death and hf) 738 50 53 302 0 in-hospital mcc (cardiac death and hf) 975 40 180 175 10 in-hospital mcc (cardiac death and hf) 1401 29 290 65 21 leon-aliz, 2014, cuba 2009 to 2010 rcs spanish 128 68± 11.5 96 24 st-elevated mi in-hospital mortality 1158 11 90 24 3 in-hospital mcc (cardiac arrest, hf, cardiogenic shock, severe dysrhythmia, re-mi, ventricular thrombus, angina) 1158 35 53 24 16 martínez garcía, 2021, cuba 2013 to 2020 pcs spanish 507 68± 11.7 347 24 st-elevated mi in-hospital mcc (cardiac arrest, hf, cardiogenic shock, severe dysrhythmia, re-mi, ventricular thrombus, angina) 1188 160 130 149 68 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 4 table 1: characteristics of included articles study data study design language sample size mean age male (n) timing of lgi (hrs) patients setting outcome cut off of lgi tp tn fp fn martínez saldaña, 2018, mexico 2016 to 2017 cross spanish 34 59.7± 13.2 29 0 stand non-stelevated mi 3-day mortality 1601 4 10 16 4 padillacueto, 2019, cuba 2011 to 2015 cross english 344 68 (5876) 226 0 st-elevated mi one-year mortality 2200 44 219 37 44 qi, 2022, china 214 to 2019 pcs english 1256 67 (53 to 78) 930 0 stand non-stelevated mi in-hospital mortality 1402 51 590 263 26 in-hospital mortality 3593 15 256 42 13 quiroga castro-a, 2010, argentina 2006 to 2007 pcs spanish 101 60 85 0 st-elevated mi in-hospital mcc (cardiac death and hf) 1600 25 50 16 10 quiroga castro-b, 2010, argentina 2007 to 2009 cross english 155 nr nr 0 st-elevated mi in-hospital mcc (cardiac death and hf) 1600 26 73 46 10 rodríguez jiménez, 2019, cuba 2012 to 2015 pcs spanish 424 67.8±14.5271 4 st-elevated mi in-hospital mortality 2122 44 220 147 13 cross: cross-sectional; fn: false negative; fp: false positive; hf: heart failure; lgi: leuko-glycemic index; mcc: major cardiac complications; mi: myocardial infarction; pcs: prospective cohort study; rcs: retrospective cohort study st: st segment; tn: true negative; tp: true positive table 2: risk of bias assessment of included studies author risk of bias applicability overall patient selection index test reference standard flow and timing patient selection index test reference standard cuesta-mero, 2021 low low low low low low low low risk diaz benitez, 2016 low low unclear low low low unclear some concern hirschson prado, 2014 low low low low low low low low risk leon-aliz; 2014 unclear low low low low low low low risk martínez garcía, 2021 low low low low low low low low risk martínez saldaña, 2018 unclear low unclear low low low low some concern padilla-cueto, 2019 unclear low low low low low low low risk qi, 2022, china low low low low low low low low risk quiroga castro-a, 2010 low low low low low low low low risk quiroga castro-b, 2010 low low low unclear low low low low risk rodríguez jiménez, 2019 low low low low low low low low risk 2.5. outcomes the sought outcomes were mortality and major cardiac complications following acute mi. the definition of major cardiac complications varied upon studies and included cardiac arrest, cardiac death, heart failure, cardiogenic shock, severe dysrhythmia, re-mi, ventricular thrombus, and angina. 2.6. risk of bias assessment since all the included studies were observational and our aim was to investigate the prognostic value of the lgi using sensitivity and specificity, the risk of bias was assessed using the quadas-2 tool (20). two reviewers independently evaluated the studies based on the items provided in the quadas-2 questionnaire and scored them as low, high, or unclear on each item. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e25 2.7. level of evidence the level of evidence was determined utilizing the grading of recommendations, assessment, development, and evaluations (grade) framework (21). through evaluation of the risk of bias, imprecision, inconsistency, indirectness, and publication bias as the items provided in the grade framework, the level of evidence was determined for each outcome. 2.8. statistical analysis the extracted data were analyzed in stata 14.0 statistical program (stata corp, college station, tx, usa). the entered data in tp, tn, fp, and fn format were analyzed using the “midas” command. all analyses were outcome-based. the prognostic value of the lgi in predicting mortality and major cardiac complications was evaluated by reporting the sensitivity, specificity, positive and negative likelihood ratio, and prognostic odds ratio with a 95% confidence interval. to assess the heterogeneity among included studies, the i2 statistic and q-test were used. publication bias was evaluated using deek’s funnel plot test. ultimately, the fagan plot diagram was depictured for the lgi in predicting mortality and major cardiac complications to assess the post-test probability and its clinical importance. we estimated pre-test probability based on pooled prevalence of mortality or major cardiac complication among included studies. 3. results 3.1. article selection a systematic search in four databases yielded 1073 nonduplicated records. following the primary screening of title and abstracts, 30 full-text articles were retrieved. in the second step, 19 articles were excluded, and the remaining 11 were selected as eligible for the meta-analysis (15, 16, 19, 2228). moreover, in a manual search, 13 potentially relevant manuscript were found. all these 13 papers were theses and did not provide sufficient data. for example, some of the 13 theses had not reported data on acute mi, not measured the primary endpoints, and not reported the required data concerning our study aims. the reasons for excluding articles are provided in figure 1. 3.2. summary of included studies among 11 eligible studies, there were 6 prospective and 1 retrospective cohort studies, along with 4 cross-sectional studies. there were 7 studies in spanish, and the remaining 4 were published in english. these studies included 3701 patients suffering from acute mi. 72.1% of enrolled patients were male. the mean age of recruited patients ranged from 59.7 years to 68.2 years. in all included studies, the lgi measurement was performed within the first 24 hours following symptoms and prior to initiation of treatments. mortality was reported in 9 studies, and the combination of major cardiac complications was present in 7 studies. the determined cut-offs for the lgi varied from 656.6 to 3593 among studies. most of the studies reported a cut-off between 1000 to 2000. the characteristics of all eligible studies have been presented in table 1. 3.3. value of the lgi in prediction of mortality analysis showed that the area under the receiver operating characteristic (roc) curve for the lgi in the prediction of mortality following acute mi was 0.77 (95% ci: 0.73 to 0.80), implicating the good value of this index (figure 2). the sensitivity and specificity of the lgi in predicting mortality were 0.75 (95% ci: 0.62 to 0.84) and 0.66 (95% ci: 0.51 to 0.78), respectively (supplementary figure 1). positive and negative likelihood ratios (positive lr and negative lr) and prognostic odds ratio were 2.20 (95% ci: 1.59 to 3.04), 0.38 (95% ci: 0.27 to 0.53), and 5.76 (95% ci: 3.60 to 9.22), respectively (supplementary figure 2 and figure 3). drawn fagan plot, based on the assumption of pre-test probability of 11% for mortality derived from the studies, revealed that the lgi’s positive and negative post-test probability were 21% and 5%, respectively (figure 4). 3.4. value of the lgi in the prediction of major cardiac complications in this section, 10 studies were included in the analysis since one study reported all-cause mortality as outcome. our analyses demonstrated that the area under the roc curve for the lgi in the prediction of major cardiac complications following acute mi was 0.81 (95% ci: 0.77 to 0.84), indicating an acceptable prognostic value for this index (figure 2). the sensitivity and specificity of the lgi in predicting major cardiac complications were 0.84 (95% ci: 0.70 to 0.92) and 0.64 (95% ci: 0.49 to 0.84), respectively (supplementary figure 3). positive lr, negative lr and prognostic odds ratio were 2.34 (95% ci: 2.21 to 3.34), 0.25 (95% ci: 0.13 to 0.45) and 9.52 (95% ci: 4.48 to 20.26), respectively (supplementary figure 4 and figure 5). drawn fagan plot based on the assumption of pre-test probability of 38% for mortality derived from the studies indicated that the lgi’s positive and negative post-test probability were 59% and 13%, respectively (figure 4). 3.5. risk of bias assessment quality assessment of included studies showed that 3 studies had unclear risk of bias regarding patient selection because of their retrospective nature. there was no clear definition of the reference standard in 2 studies, which made their status unclear in this item. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 6 figure 1: flow diagram of the current study. cabg: coronary artery bypass graft; mcc: major cardiac complications. figure 2: summary receiver operating characteristics (sroc) curves of leuko-glycemic index in predication of mortality and major cardiac complications following acute myocardial infarction. auc: area under the curve; spec: specificity; sens: sensitivity. moreover, flow and timing could not be deduced from one study, causing it to be regarded as unclear. finally, one study had not presented adequate data about the applicability of reference standards, which is thus considered unclear. in all remaining items, studies were low-risk. the overall risk of bias assessment was concluded as low in 9 studies and some concern in 2 studies (table 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e25 figure 3: odds ratio of leuko-glycemic index in predication of mortality following acute myocardial infarction. ci: confidence interval. table 3: certainty of evidence based on grade framework outcome sample size prognostic odds ratio risk of bias imprecision inconsistency (i2) indirectness publication bias judgment and level of evidence mortality 3646 5.76 (95% ci: 3.60, 9.22) not serious not serious serious not serious not present moderate: rated down 1 point • presence of serious inconsistency rated up 2 points • very large magnitude of effect* major cardiac complications 2430 9.52 (95% ci: 4.48, 20.26) not serious not serious serious not serious likely low: rated down 2 points • presence of serious inconsistency • possible publication bias rated up 2 points • very large magnitude of effect* *, according to prognostic odds ratio. grade: grading of recommendations, assessment, development, and evaluations; ci: confidence interval. 3.6. publication bias deek’s funnel plot revealed no publication bias among studies reporting the value of the lgi in predicting mortality following acute mi (p=0.48). however, there was evidence of publication bias in articles that surveyed major cardiac complications (p=0.03) (supplementary figure 5). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 8 figure 4: fagan plots of leuko-glycemic index in predication of mortality and major cardiac complications following acute myocardial infarction. lr: likelihood ratio; prob: probability; post-prob-pos: positive post-test probability; post-prob-neg: negative post-test probability. 3.7. certainty of evidence there was serious inconsistency in assessment of the prognostic value of lgi in prediction of mortality, while a very large magnitude of effect was observed (prognostic odds ratio=5.76). therefore, level of evidence was graded as moderate. presence of serious inconsistency and possible publication bias rated down certainty of evidence two points in assessment of prognostic value of lgi in predicting major cardiac complication. however, a very large magnitude of effect was observed (prognostic odds ratio=9.52). therefore, the level of evidence was deemed low (table 3). 4. discussion previous studies implicated a close link between admission hyperglycemia, regardless of diabetic status, and the shortterm and long-term mortality among patients suffering from myocardial infarction (29, 30). similarly, a greater leukocyte count on admission, which is representative of inflammation in the body, was associated with poor outcomes in st segment elevation mi (stemi) patients (31). with the backbone of mentioned findings, in 2010, quiroga castro et al. introduced the combination of two variables of blood glucose and leukocyte count as the leuko-glycemic index for predicting mortality and complications among mi patients (14). since then, multiple studies have been conducted to survey the predictive value of the leuko-glycemic index. hence, for the first time, we conducted a systematic review and metaanalysis to assess all studies available on this subject. the present study demonstrated that the leuko-glycemic index has favorable sensitivity and accepted specificity in predicting in-hospital mortality among mi patients, irrespective of diabetes status. these results should be interpreted cautiously since the leuko-glycemic index is subject to limitations. some studies demonstrated a difference in the predictive value of the leuko-glycemic index in diabetic and nondiabetic patients (15). even though diabetes, per se, is asthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e25 figure 5: odds ratio of leuko-glycemic index in predication of major cardiac complications following acute myocardial infarction. ci: confidence interval. sociated with a higher burden of cardiovascular morbidity and mortality, it would be reasonable to use different cutoff points as baseline average blood glucose and its alteration in diabetic patients differ from nondiabetic patients. nevertheless, the detrimental effect of hyperglycemia, regardless of diabetic status, persists even in response to treatment (32). according to the estimated results, the lgi had 84% sensitivity and 64% specificity in predicting major cardiac complications in patients suffering from myocardial infarction. but based on the pre-test and post-test probability, the leuko-glycemic index does not significantly impact clinical decision-making. in a systematic review and meta-analysis, admission hyperglycemia was associated with a higher risk of overall arrhythmias, which is the cause of early complications following mi in diabetic and nondiabetic patients (35). blood glucose levels and inflammatory markers are tethered together. hyperglycemia is associated with higher concentrations of inflammatory cytokines that play a significant role in the secondary perpetuation of myocardial damage after mi (16, 19, 34). inflammatory markers’ increase after mi is linked to hypercoagulability, myocardial remodeling, and oxidative stress, culminating in adverse clinical events (35). we acknowledge the presence of limitations in our study. primary endpoints of major cardiac complications and their follow-up periods varied among studies, and there was a lack of consensus. this heterogeneity in the definition of measured outcomes contributes to the wide range of reported cutoff points among referred studies. the majority of studies included in the meta-analysis have a small sample size, with a maximum of 1256 patients in the most recent one. during our investigations, we found a sparsity of studies comparing the leuko-glycemic index with other prognostic indicators such as the timi, heart, and grace scores. in addition, most of the studies found in the literature were conducted on the hispanic/latino populations, which raised concerns about geographical and ethnic bias. further studies with robust methodology and racial diversity are warranted to address these limitations. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 10 5. conclusion in the absence of advanced diagnostic modalities, the leukoglycemic index could be an assistive tool for predicting inhospital mortality of mi patients due to its availability, routine measurement, and low cost. however, the calculation of the leuko-glycemic index would not be clinically impressive regarding the major cardiac complications after mi. these conclusions are made on studies mainly investigating latino/hispanic populations, and their applicability to other populations is under question. future studies are required to compare the other well-known predictive scores with the leuko-glycemic index. 6. declarations 6.1. acknowledgments none. 6.2. conflict of interest the authors declare that there is no conflict of interest. 6.3. fundings and supports this study has been funded and supported by shahid beheshti university of medical sciences. 6.4. authors’ contribution study design: as, rs, saf dara gathering: saf, mv, sr analysis: saf interpreting the results: as, rs drafting: rs, saf, sr critically revised: all authors read and approve final version: all authors references 1. roth ga, mensah ga, johnson co, addolorato g, ammirati e, baddour lm, et al. global burden of cardiovascular diseases and risk factors, 1990-2019: update from the gbd 2019 study. j am coll cardiol. 2020;76(25):29823021. 2. khan ma, hashim mj, mustafa h, baniyas my, al suwaidi s, alkatheeri r, et al. global epidemiology of 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the american heart association diabetes committee of the council on nutrition, physical activity, and metabolism. circulation. 2008;117(12):1610-9. 31. terlecki m, bednarek a, kawecka-jaszcz k, czarnecka d, bryniarski l. acute hyperglycaemia and inflammation in patients with st segment elevation myocardial infarction. kardiol pol. 2013;71(3):260-7. 32. singh k, hibbert b, singh b, carson k, premaratne m, le may m, et al. meta-analysis of admission hyperglycaemia in acute myocardial infarction patients treated with primary angioplasty: a cause or a marker of mortality? eur heart j cardiovasc pharmacother. 2015;1(4):220-8. 33. trongtorsak a, kewcharoen j, thangjui s, yanez-bello ma, sous m, prasai p, et al. admission hyperglycemia in acute myocardial infarction is associated with an increased risk of arrhythmias: a systematic review and meta-analysis. j arrhythm. 2022;38(3):307-315. 34. esposito k, nappo f, marfella r, giugliano g, giugliano f, ciotola m, et al. inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. circulation. 2002;106(16):2067-72. 35. granger cb, kochar a. understanding and targeting inflammation in acute myocardial infarction: an elusive goal. j am coll cardiol. 2018. p. 199-201. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 12 supplementary material 1: full search syntax of the current study pubmed 1"glycemic index"[mesh terms] or ("leuko*"[all fields] and "glycemic"[title/abstract]) or "leuko-glycemic"[title/abstract] or "leuko-glycemic"[title/abstract] or "leukoglycemic"[title/abstract] 2“myocardial ischemia”[mesh terms] or “acute coronary syndrome”[mesh terms] or “angina pectoris”[mesh terms] or “angina, stable”[mesh terms] or “angina, unstable”[mesh terms] or “coronary artery disease”[mesh terms] or “coronary occlusion”[mesh terms] or “coronary stenosis”[mesh terms] or “coronary thrombosis”[mesh terms] or “coronary vasospasm”[mesh terms] or “myocardial infarction”[mesh terms] or “anterior wall myocardial infarction”[mesh terms] or “inferior wall myocardial infarction”[mesh terms] or “non-st elevated myocardial infarction”[mesh terms] or “st elevation myocardial infarction”[mesh terms] or “myocardial reperfusion injury”[mesh terms] or “myocardial ischemia”[title/abstract] or “ischemic heart disease”[title/abstract] or “acute coronary syndrome”[title/abstract] or “unstable angina”[title/abstract] or “angina pectoris”[title/abstract] or “angina pectori”[title/abstract] or “preinfarction angina”[title/abstract] or “coronary heart disease”[title/abstract] or “coronary artery disease”[title/abstract] or “coronary arteriosclerosis”[title/abstract] or “coronary atherosclerosis”[title/abstract] or “coronary occlusion”[title/abstract] or “coronary stenosis”[title/abstract] or “coronary thrombosis”[title/abstract] or “coronary vasospasm”[title/abstract] or “myocardial infarction”[title/abstract] or “myocardial infarct”[title/abstract] or “heart attack”[title/abstract] or “myocardial reperfusion injury”[title/abstract] or “myocardial ischemic reperfusion injury”[title/abstract] or “heart infarction”[title/abstract] or “acute heart infarction”[title/abstract] or “anterior myocardial infarction”[title/abstract] or “dressler syndrome”[title/abstract] or “heart muscle necrosis”[title/abstract] or “inferior myocardial infarction”[title/abstract] or “minoca”[title/abstract] or “non st segment elevation myocardial infarction”[title/abstract] or “posterior myocardial infarction”[title/abstract] or “silent myocardial infarction”[title/abstract] or “st segment elevation myocardial infarction”[title/abstract] or “acute coronary syndrome”[title/abstract] or “non st segment elevation acute coronary syndrome”[title/abstract] or “acute coronary syndrome”[title/abstract] or “angina pectoris”[title/abstract] or “cardiac allograft vasculopathy”[title/abstract] or “coronary artery atherosclerosis”[title/abstract] or “coronary artery constriction”[title/abstract] or “coronary artery obstruction”[title/abstract] or “coronary artery thrombosis”[title/abstract] or “coronary subclavian steal syndrome”[title/abstract] or “heart infarction”[title/abstract] or “ischemic cardiomyopathy”[title/abstract] or “kounis syndrome”[title/abstract] or “myocardial hibernation”[title/abstract] or “no reflow phenomenon”[title/abstract] or “silent myocardial ischemia”[title/abstract] or “takotsubo cardiomyopathy”[title/abstract] 3#1 and #2 embase 1’glycemic index’/exp or ’leuko*glycemic’:ab,ti or ’leuko-glycemic’:ab,ti or ’leukoglycemic’:ab,ti 2‘heart infarction’/exp or ‘acute heart infarction’/exp or ‘anterior myocardial infarction’/exp or ‘dressler syndrome’/exp or ‘heart atrium infarction’/exp or ‘heart infarction size’/exp or ‘heart muscle necrosis’/exp or ‘heart reinfarction’/exp or ‘heart ventricle infarction’/exp or ‘impending heart infarction’/exp or ‘inferior myocardial infarction’/exp or ‘minoca’/exp or ‘non st segment elevation myocardial infarction’/exp or ‘posterior myocardial infarction’/exp or ‘silent myocardial infarction’/exp or ‘st segment elevation myocardial infarction’/exp or ‘acute coronary syndrome’/exp or ‘non st segment elevation acute coronary syndrome’/exp or ‘acute coronary syndrome’/exp or ‘angina pectoris’/exp or ‘cardiac allograft vasculopathy’/exp or ‘coronary artery atherosclerosis’/exp or ‘coronary artery constriction’/exp or ‘coronary artery obstruction’/exp or ‘coronary artery thrombosis’/exp or ‘coronary subclavian steal syndrome’/exp or ‘heart infarction’/exp or ‘heart muscle ischemia’/exp or ‘ischemic cardiomyopathy’/exp or ‘kounis syndrome’/exp or ‘myocardial hibernation’/exp or ‘no reflow phenomenon’/exp or ‘silent myocardial ischemia’/exp or ‘takotsubo cardiomyopathy’/exp or ‘myocardial ischemia’:ab,ti or ‘ischemic heart disease’:ab,ti or ‘acute coronary syndrome’:ab,ti or ‘unstable angina’:ab,ti or ‘angina pectoris’:ab,ti or ‘angina pectori’:ab,ti or ‘preinfarction angina’:ab,ti or ‘preinfarction anginas’:ab,ti or ‘coronary heart disease’:ab,ti or ‘coronary artery disease’:ab,ti or ‘coronary arteriosclerosis’:ab,ti or ‘coronary atherosclerosis’:ab,ti or ‘coronary occlusion’:ab,ti or ‘coronary stenosis’:ab,ti or ‘coronary thrombosis’:ab,ti or ‘coronary vasospasm’:ab,ti or ‘myocardial infarction’:ab,ti or ‘myocardial infarct’:ab,ti or ‘heart attack’:ab,ti or ‘myocardial reperfusion injury’:ab,ti or ‘myocardial ischemic reperfusion injury’:ab,ti or ‘heart infarction’:ab,ti or ‘acute heart infarction’:ab,ti or ‘anterior myocardial infarction’:ab,ti or ‘dressler syndrome’:ab,ti or ‘heart atrium infarction’:ab,ti or ‘heart infarction size’:ab,ti or ‘heart muscle necrosis’:ab,ti or ‘heart reinfarction’:ab,ti or ‘heart ventricle infarction’:ab,ti or ‘impending heart infarction’:ab,ti or ‘inferior myocardial infarction’:ab,ti or ‘minoca’:ab,ti or ‘non st segment elevation myocardial infarction’:ab,ti or ‘posterior myocardial infarction’:ab,ti or ‘silent myocardial infarction’:ab,ti or ‘st segment elevation myocardial infarction’:ab,ti or ‘acute coronary syndrome’:ab,ti or ‘non st segment elevation acute coronary syndrome’:ab,ti or ‘acute coronary syndrome’:ab,ti or ‘angina pectoris’:ab,ti or ‘cardiac allograft vasculopathy’:ab,ti or ‘coronary artery atherosclerosis’:ab,ti or ‘coronary artery constriction’:ab,ti or ‘coronary artery obstruction’:ab,ti or ‘coronary artery thrombosis’:ab,ti or ‘coronary subclavian steal syndrome’:ab,ti or ‘heart infarction’:ab,ti or ‘heart muscle ischemia’:ab,ti or ‘ischemic cardiomyopathy’:ab,ti or ‘kounis syndrome’:ab,ti or ‘myocardial hibernation’:ab,ti or ‘no reflow phenomenon’:ab,ti or ‘silent myocardial ischemia’:ab,ti or ‘takotsubo cardiomyopathy’:ab,ti 3#1 and #2 scopus 1title-abs-key(“glycemic index” or “leuko*glycemic” or “leuko-glycemic” or “leukoglycemic”) 2title-abs-key(“myocardial ischemia” or “ischemic heart disease” or “acute coronary syndrome” or “unstable angina” or “angina pectoris” or “angina pectori” or “preinfarction angina” or “preinfarction anginas” or “coronary heart disease” or “coronary artery disease” or “coronary arteriosclerosis” or “coronary atherosclerosis” or “coronary occlusion” or “coronary stenosis” or “coronary thrombosis” or “coronary vasospasm” or “myocardial infarction” or “myocardial infarct” or “heart attack” or “myocardial reperfusion injury” or “myocardial ischemic reperfusion injury” or “heart infarction” or “acute heart infarction” or “anterior myocardial infarction” or “dressler syndrome” or “heart atrium infarction” or “heart infarction size” or “heart muscle necrosis” or “heart reinfarction” or “heart ventricle infarction” or “impending heart infarction” or “inferior myocardial infarction” or “minoca” or “non this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e25 supplementary material 1: full search syntax of the current study st segment elevation myocardial infarction” or “posterior myocardial infarction” or “silent myocardial infarction” or “st segment elevation myocardial infarction” or “acute coronary syndrome” or “non st segment elevation acute coronary syndrome” or “acute coronary syndrome” or “angina pectoris” or “cardiac allograft vasculopathy” or “coronary artery atherosclerosis” or “coronary artery constriction” or “coronary artery obstruction” or “coronary artery thrombosis” or “coronary subclavian steal syndrome” or “heart infarction” or “heart muscle ischemia” or “ischemic cardiomyopathy” or “kounis syndrome” or “myocardial hibernation” or “no reflow phenomenon” or “silent myocardial ischemia” or “takotsubo cardiomyopathy”) 3#1 and #2 web of science (ts=(“glycemic index” or “leuko*glycemic” or “leuko-glycemic” or “leukoglycemic”)) and ts=( “myocardial ischemia” or “ischemic heart disease” or “acute coronary syndrome” or “unstable angina” or “angina pectoris” or “angina pectori” or “preinfarction angina” or “preinfarction anginas” or “coronary heart disease” or “coronary artery disease” or “coronary arteriosclerosis” or “coronary atherosclerosis” or “coronary occlusion” or “coronary stenosis” or “coronary thrombosis” or “coronary vasospasm” or “myocardial infarction” or “myocardial infarct” or “heart attack” or “myocardial reperfusion injury” or “myocardial ischemic reperfusion injury” or “heart infarction” or “acute heart infarction” or “anterior myocardial infarction” or “dressler syndrome” or “heart atrium infarction” or “heart infarction size” or “heart muscle necrosis” or “heart reinfarction” or “heart ventricle infarction” or “impending heart infarction” or “inferior myocardial infarction” or “minoca” or “non st segment elevation myocardial infarction” or “posterior myocardial infarction” or “silent myocardial infarction” or “st segment elevation myocardial infarction” or “acute coronary syndrome” or “non st segment elevation acute coronary syndrome” or “acute coronary syndrome” or “angina pectoris” or “cardiac allograft vasculopathy” or “coronary artery atherosclerosis” or “coronary artery constriction” or “coronary artery obstruction” or “coronary artery thrombosis” or “coronary subclavian steal syndrome” or “heart infarction” or “heart muscle ischemia” or “ischemic cardiomyopathy” or “kounis syndrome” or “myocardial hibernation” or “no reflow phenomenon” or “silent myocardial ischemia” or “takotsubo cardiomyopathy”) supplementary figure 1: sensitivity and specificity of leuko-glycemic index in predication of mortality following acute myocardial infarction. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 14 supplementary figure 2: positive and negative likelihood ratio (lr) of leuko-glycemic index in predication of mortality following acute myocardial infarction. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e25 supplementary figure 3: sensitivity and specificity of leuko-glycemic index in predication of major cardiac complications following acute myocardial infarction. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. sadeghi et al. 16 supplementary figure 4: positive and negative likelihood ratio (lr) of leuko-glycemic index in predication of major cardiac complications following acute myocardial infarction. ci: confidence interval. supplementary figure 5: publication bias in assessment of leuko-glycemic index in prediction of mortality and major cardiac complications following acute myocardial infarction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e53 or i g i n a l re s e a rc h determinants of prolonged length of stay in the emergency department; a cross-sectional study seyed mohammad hosseininejad1, hamed aminiahidashti2∗, seyede masoume pashaei2, iraj goli khatir2, seyed hosein montazer2, farzad bozorgi3, fahime mahmoudi4 1. department of emergency medicine, diabetes research center, faculty of medicine, mazandaran university of medical sciences, sari, iran. 2. department of emergency medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran. 3. emergency department, orthopedic research center, faculty of medicine, mazandaran university of medical sciences, sari, iran. 4. faculty of medicine, mazandaran university of medical sciences, sari, iran. received: august 2016; accepted: november 2016; published online: 18 january 2017 abstract: introduction: timeliness has been considered as a key domain in quality of emergency department (ed) care and delay in care providing is influential determinants of patient’s outcomes. the present study, aimed to evaluate the determinants of prolonged ed length of stay (los). methods: in this cross-sectional study, using adopted version of the latest form for external evaluation and accreditation of eds introduced by iranian ministry of health, determinants of prolonged los were evaluated in the ed of an educational hospital. using spss 11, multivariate binary logistic regression was applied to estimate adjusted odds ratios (or) for determining factors associated with prolonged los. results: 162 (10.2%) cases with prolonged los were detected. based on univariate analysis, female gender (or: 1.42, 95% ci: 1.14-1.75, p = 0.001), older age (or: 1.05, 95% ci: 1.02-1.08, p < 0.0001), admission on evening shifts (or: 4.0; 95% ci: 1.84-8.68, p < 0.001), triage level i (or: 1.76, 95% ci: 1.21-2.57, p = 0.003), lack of insurance support (or: 1.56, 95% ci: 1.12-2.19, p = 0.010), higher number of ordered para-clinical tests (or: 1.23, 95% ci: 1.11-1.37, p = 0.016), and disposition time > 6 hours (or, 0.13, p < 0.0001), were significant risk factors of prolonged los. conclusion: older age, lack of insurance support, disposition time > 6 hours due to complexity of patients’ complaint, and the necessity of repeated para-clinical measures were the most important reasons for failed provision of timely services. from the view point of ed personnel, a small part of prolonged los in ed was concerned with defective ed workflow, while, the most important cause of such delays was the delayed response of the consultancy services. keywords: emergency service, hospital; length of stay; quality of health care; risk factors; iran © copyright (2017) shahid beheshti university of medical sciences cite this article as: hosseininejad sm, aminiahidashti h, pashaei s-m, goli khatir i, montazer sh, bozorgi f, mahmoudi f. determinants of prolonged length of stay in the emergency department; a cross-sectional study. emergency. 2017; 5(1): e53. 1. introduction e mergency department (ed) crowding is a chronic health challenge worldwide (1). this growing challenge could results in curtailed and dysfunctional emergency activities (2, 3). it has bidirectional synergic association with delayed emergency care (2). both crowding and delays in ed cares are influential determinants of patient’s outcome (4). therefore, they affect ed performance, mainly ∗corresponding author: hamed aminiahidashti; department of emergency medicine, imam khomeini hospital, amir mazandarani bolivar, sari, iran. tel: +989113540546; email: hamedaminiahidashti@yahoo.com regarding timeliness (5). timeliness has been considered as a key domain in quality of emergency care. by timely we mean that eds should continuously move toward “reducing waits and sometimes harmful delays for both those who receive and those who give care”(5). to achieve acceptable timeliness and high quality emergency care, the period from patient’s arrival to discharge could be segmented, determinants of each segment should be identified, and then evidencebased interventions may be introduced. in recent years, several interventions including employing emergency specialists, holding formal interdisciplinary team-work training programs, use of triage systems, fast-track units, and maximum length of stay (los) rules, e.g. 4-hour rule in the uk, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. hosseininejad et al. 2 have been introduced to reduce waits and delays in ed (69). in iran, population aging has resulted in a rising number of admissions to eds (3, 10). accordingly, improvement of performance in eds is an urgent challenge. recently, a set of rules have been introduced by iranian ministry of health and medical education (imoh), regarding waiting times or los in ed, and eds are encouraged to achieve these targets (11). in addition, iranian researchers have focused on the los and shown that the average los of patients admitted to teaching eds has been much more than the maximum targeted los (los<6 hours), introduced by imoh as a safe los (11, 12). however, a growing body of evidence demonstrated that focusing on a set of pre-specified time rules could lead to unintended detracts from clinical priorities and, consequently, attenuation of patient-centeredness and poor outcomes (1315). in spite of dozens of reports on ed performance evaluation from iran, data on the causes of lower ed performance and, specially, prolonged los are scarce. therefore, this study aimed to evaluate determinants of prolonged los in emergency department. 2. methods 2.1. study design and setting in this cross-sectional study, using adopted version of the latest form for external evaluation and accreditation of eds introduced by imoh, determinants of prolonged los were evaluated in ed of imam khomeini educational hospital, sari, iran, during three months from november 2014 to february 2015. applied procedures and data collection methods in this study were approved by the ethics committee of mazandaran university of medical sciences (ethical approval number: 854). authors adhered to the all ethical principles of helsinki declaration and confidentiality of patients’ records. 2.2. participants patients who had stayed in the ed for more than 6 hours were considered as cases of prolonged los and were enrolled to the study using a sequential convenience sampling. eligible patients were selected from the lists of all patients admitted to the ed, every 60 hours. los was calculated according to the following equation: los = time of medical record review time of admission. imam khomeini hospital is a teaching hospital affiliated to mazandaran university of medical sciences. it is the most equipped hospital throughout mazandaran province, and consequently, emergency patients are admitted to its ed, either by pre-hospital emergency teams, by themselves or their caregivers, or by other hospitals or clinics. this ed has been administered by an experienced emergency specialist and benefited from highly competent nurses and staff. according to guidelines provided by imoh, the emergency severity index (esi) is used for patients’ triage in this ed. 2.3. data gathering data gathering was done using an adopted version of the latest form for external evaluation and accreditation of eds at teaching hospitals introduced by imoh. the adoption process was done in a team including emergency specialists and highly competent ed staff. the first version of this checklist was used in two pilot studies and some corrections were made according to field experiences. the final version was designed in three sections including the demographic and background section, a section for indices of timely care, and a section for measuring causes of prolonged los. its face validity was confirmed by a team of experts in emergency medicine. regarding its reliability, we estimated cronbach’s alpha as 77.0, which revealed an acceptable reliability. the data were extracted by retrospective review of medical records, interview with the patient’s doctor, and also supervisor nurses at the time of presence of the patient in the ed. first and second sections of the study checklist were completed according to medical records, while causes of prolonged los were determined by in-depth interviews. interviewees were asked to select causes of prolonged los of each patient according to the study checklist. a prolonged los could be considered owing to more than one cause. the number of prolonged los assigned to each cause was counted and then categorized during a review session by the research team. data were collected by three medical students who were trained through a series of educational sessions. during the first session, the study checklist was introduced to students and completed for selected patients. in the next role playing sessions, they were asked to complete the checklists for several complicated patients who were purposefully assigned. then, the completed checklists were discussed and students’ competency was assessed by the principal investigator, smh. the data were reviewed by our principal investigator in weekly sessions. missing and inconsistent data were specified and corrected according to medical records or ad hoc interviews, if applicable. 2.4. statistical analysis data were computerized and analyzed using statistical package for social sciences (spss) version 11.0. data was cleaned and prepared according to recommended procedures (16) and descriptive statistics was applied to describe the data. variable reduction was conducted using univariate statistical tests, considering p value ≤ 0.25 (17). then, multivariate binary logistic regression was applied to estimate adjusted odds ratios (or) and its 95% confidence intervals (ci) for associated factors with prolonged los. in this step, a p-value less than 0.05 was considered as statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e53 figure 1: reasons for visiting the emergency department among patients with prolonged length of stay (n = 162). table 1: baseline characteristics of patients with prolonged length of stay in the emergency department variable n (%) gender male 71(43.8) female 91(56.2) transferred by ambulance 130(80.2) caregivers 26(16.1) referred 6(3.7) insurance support yes 141(87.0) no 21(13.0) triage level* i 2(1.2) ii 7(4.3) iii 127(78.4) iv 12(7.4) missing 14(8.6) admission work shift night 88(54.3) evening 40(24.7) morning 34(21.0) *: based on emergency severity score (esi). 3. results 3.1. baseline characteristics 1581 patients were admitted to the ed during the study period. 162 (10.2%) cases of prolonged los with the mean age of 58.5 ± 20.2 (range: 12-98) years were detected (56.2% female). table 1 shows the baseline characteristics of these 162 cases. 80.2% patients had been brought to the ed by caregivers and 78.4% had triage level of iii. figure 1 displays the reasons for visiting ed among patients with prolonged los. mean waiting time from arrival to the first nursing visit was 2.85 ± 1.75 minutes (1 – 8), while mean time before the first visit by a doctor was 3.4 ± 2.7 minutes (1 – 11). 153 (94.4%) cases had disposition order within the first 6 hours of admission. 3.2. determinants of prolonged los based on univariate analysis, female gender (or: 1.42, 95% ci: 1.14-1.75, p = 0.001), older age (or: 1.05, 95% ci: 1.021.08, p < 0.0001), admission on evening shifts (or: 4.0; 95% ci: 1.84-8.68, p < 0.001), triage level i (or: 1.76, 95% ci: 1.212.57, p = 0.003), lack of insurance support (or: 1.56, 95% ci: 1.12-2.19, p = 0.010), higher number of ordered para-clinical tests (or: 1.23, 95% ci: 1.11-1.37, p = 0.016), and disposition time > 6 hours (or, 0.13, p < 0.0001), were significant risk factors of prolonged los. patients had a 5% higher risk of prolonged los for every 5-year increase in their age. based on the results of multivariate analysis, older age (p = 0.019), lack of insurance support (p = 0.024), disposition time > 6 hours (p = 0.003), and higher number of ordered para-clinical tests (p = 0.029) were significantly associated with prolonged los (table 2). 3.3. causes of prolonged los based on ed personnel’s view point according to ed physicians and supervisor nurses, causes of prolonged los in these 162 cases could be categorized into ed-related factors, poor cooperation of other departments, and factors outside of the hospital (table 3). 4. discussion according to the findings of the present study, older age, lack of insurance support, disposition time > 6 hours, and higher number of ordered para-clinical tests were among the most important determinants of prolonged los. on the view point of ed personnel poor cooperation of other departments in providing proper consultancy and patients’ disposition, as well as some factors inside the ed, such as delayed consult request, complicated cases, untimely admission, and crowding, were among the most frequent causes of prolonged los in the studied ed. more precisely, according to the medical and nursing staff reports, the cause of prolonged los, in many cases, is the delayed response by the departments with which the ed maintains interactions in order to provide proper services. meanwhile, 6 percent of the prolonged los was caused as a result of defects in the ed’s workflow and ed crowding. however, this may be due to the bias of interviewees (18). yet, considering the fact that they were asked to be honest in their statements, this bias is unlikely to be significant. although, at first glance, the quantitative results differed from the causes stated by the medical and nursing staff, when we look closer, the two have largely this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. hosseininejad et al. 4 table 2: determinants of prolonged length of stay in the emergency department based on multivariate analysis factors crude or adjusted or p older age 1.05(1.02-1.08) 1.10(1.02-1.20) 0.019 having insurance support 0.64(0.46-0.89) 0.29(0.10-0.85) 0.024 disposition time ≤ 6 hours 0.13(0.02-0.99) 0.03(0.003-0.30) 0.003 higher number of para-clinical tests 1.23(1.11-1.37) 1.3(1.03-1.64) 0.029 odds ratios (or) were presented with 95% confidence interval. table 3: sources of prolonged length of stay based on the emergency department personnel’s view point factors number (%)1 inside the emergency department (n = 20) delayed request for consult 15 (75.0) complicated cases 5 (25.0) untimely admission 16 (80.0) crowding 2 (10.0) poor cooperation of other departments2 (n=114 ) gastroenterology 21 (18.4) respiratory 12 (10.5) nephrology 9 (7.8) surgery 9 (7.8) orthopedic 3 (2.6) internal medicine 35 (30.7) oncology 7 (6.1) endocrinology 12 (10.5) neurosurgery 7 (6.1) cardiovascular 6 (5.3) outside the hospital (n=28 ) outside consult3 23 (82.1) imaging4 17 (60.7) 1: length of stay could be prolonged due to more than onesource. 2: for patients disposition. 3: consulting with department outside the hospital such as neurology, infectious diseases, cardiovascular, and toxicology. 4: computed tomography scan (ct), magnetic resonanceimaging (mri), and ultrasonography. confirmed each other. for instance, older age can increase the risk of co-morbidity and complexity of clinical decisionmaking (19), and may, eventually, delay the response by the consultancy services. also, lack of insurance coverage can indicate lower socioeconomic status, increasing the risk of co-morbidity and complexity of clinical decision-making (20, 21), and eventually, delaying the response by the consultancy services. as for patients in need of repeated paraclinical measures, the consultancy services couldn’t provide proper consultation prior to receiving the respective results, hence, the delayed response by the mentioned services. on the other hand, a part of the delayed response of the consultancy services can be associated with the reasons other than what had entered the quantitative analysis. it is possible, for instance, that defective capabilities of the staff in constructive interdisciplinary interaction (22), crowding of public medical centers while implementing the healthcare reform initiative (23), technical problems of the employed equipment in paraclinical centers, and shortage of the required materials in such centers, had seriously influenced the delay of different services for timely response to the ed. it is, therefore, suggested that the reasons for delayed response of the consultancy services be examined in a study. our results showed that the los of a few patients has been prolonged due to ed crowding. this might indicate the insufficiency of the number of the staff and their adequate skills in providing timely services. that being the case, establishing a new ed in the study site is not necessary for the time being, however, designing proper interventions to obviate ed crowding can definitely prove helpful. yet, considering the aging population in iran (10), the effect of older age in prolonged los can be a warning for an increase in ed crowding (24), followed by increased ratio of patients with prolonged los in near future. although the generalizability of our results can be influenced by regional differences concerning the staff’s capabilities for interdisciplinary interaction and cooperation (25), regional infrastructures and development, population care patterns, and patient distribution, but since sari, is among the fairly developed iranian cities, we hope that the results of this study are generalizable to most iranian eds, especially this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e53 those situated in areas with populations below one million. in any case, further studies can reveal the generalizability of our findings. 5. limitation unfortunately, we couldn’t manage to conduct prospective follow-up of the patients admitted to the ed to determine the outcome of patients with prolonged los, as well as, their distribution by time of discharge. considering the conditions of the patients and also the nature and limitations of the study, we failed to contact the patients to collect more data. we also couldn’t examine, with adequate accuracy, the contributing factors and causes of disposition after 6 hours from admission. we believe these limitations can be objectives for further studies. 6. conclusion older age, lack of insurance support, disposition time > 6 hours due to complexity of patients’ complaint, and the necessity of repeated para-clinical measures were the most important reasons for failed provision of timely services. on the view point of ed personnel, a small part of prolong ed length of stay was concerned with defective ed workflow, while, the most important cause of such delays was the delayed response of the consultancy services. 7. appendix 7.1. acknowledgements: the authors wish to thank the staff of emergency department of imam khomeini hospital of sari for their valuable contribution in data gathering. 7.2. author contribution: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding: this study was funded by mazandaran university of medical sciences. 7.4. conflict of interest: none. references 1. higginson i. emergency department crowding. emergency medicine journal. 2012;29(6):437-43. 2. hoot nr, aronsky d. systematic review of emergency department crowding: causes, effects, and solutions. annals of emergency medicine. 2008;52(2):126-36. e1. 3. pines jm, mullins pm, cooper jk, feng lb, roth ke. national trends in emergency department use, care patterns, and quality of care of older adults in the united states. journal of the american geriatrics society. 2013;61(1):12-7. 4. pines jm, hollander je. emergency department 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dukes ka, et al. error reduction and performance improvement in the emergency department through formal teamwork training: evaluation results of the medteams project. health services research. 2002;37(6):1553-81. 23. hashemi b, baratloo a, forouzafar mm, motamedi m, tarkhorani m. patient satisfaction before and after executing health sector evolution plan. iranian journal of emergency medicine. 2015;2(3):127-33. 24. naughton c, drennan j, treacy p, fealy g, kilkenny m, johnson f, et al. the role of health and non-healthrelated factors in repeat emergency department visits in an elderly urban population. emergency medicine journal. 2010;27(9):683-7. 25. moss je, flower cl, houghton lm, moss dl, nielsen da, taylor dm. a multidisciplinary care coordination team improves emergency department discharge planning practice. medical journal of australia. 2002;177(8):435-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e75 or i g i n a l re s e a rc h saline flush versus chest x ray in confirmation of central venous catheter placement; a diagnostic accuracy study mehrdad esmailian1∗, reza azizkhani1, nazila najafi2 1. emergency medicine research center, department of emergency medicine, al-zahra research institute, isfahan university of medical sciences, isfahan, iran. 2. emergency department, student research committee, faculty of medicine, isfahan university of medical sciences, isfahan, iran. received: july 2017; accepted: august 2017; published online: 8 august 2017 abstract: introduction: central venous catheterization (cvc) is a commonly performed procedure in critically ill patients of emergency department. this study was designed to compare the diagnostic accuracy of saline flush with cxr in confirmation of above-the-diaphragm cvc placement. methods: this prospective cross sectional study was conducted on adult patients in need of cvc placement in emergency department. placement confirmation was performed with saline flush method and cxr, then chest computed tomography (ct) was performed as the gold standard. the screening performance characteristics of the two methods were calculated and compared using spss 21 and stata 11. results: 103 cases with the mean age of 57.18±9.3 (35 -80) years were studied (52.4% male). the mean duration of procedure was 2.5±1.24 in saline flush and 32.11±5.52 minutes in cxr method (p<0.001(. the area under the roc curves for saline flush and cxr in confirmation of cvc placement were 0.90 (95%ci: 0.70 0.100) and 0.80 (95%ci: 0.55 0.100), respectively (p = 0.317). the sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of saline flush were 80%, 100%, 100, 98.9%, infinity, and 0.01, respectively. these measures were 60%, 100%, 100%, 98%, infinity, and 0.02 for cxr, respectively. conclusion: it seems that saline flush method could be considered as a safe, rapid, and accurate bedside method for cvc placement confirmation in emergency department. keywords: catheterization, central venous; sensitivity and specificity; ultrasonography, interventional; diagnostic imaging; chest x ray © copyright (2017) shahid beheshti university of medical sciences cite this article as: esmailian m, azizkhani r, najafi n. saline flush versus chest x ray in confirmation of central venous catheter placement; a diagnostic accuracy study. emergency. 2017; 5(1): e75. 1. introduction c entral venous catheter (cvc) placement is a commonly performed procedure for critically ill patients in emergency department. it is indicated for different purposes including central venous pressure (cvp) monitoring, infusion of vasoactive agents, administration of blood products, parenteral nutrition, and etc. cvc placement requires training and experience and is not risk-free for patients, even when performed by skilled professionals. cvc misplacement is a well-known technical error that has been described in approximately 7% of cases and causes serious complications such as haematoma, pneumothorax, catheter ∗corresponding author: mehrdad esmailian; emergency department, al-zahra hospital, soffeh boulevard, isfahan, iran. email: mehrdad13972@yahoo.com tel: 00989133277884 wedging, erosion or perforation of vessel walls, local venous thrombosis, catheter dysfunction, and cranial retrograde injection (1, 2). several techniques have been proposed to detect cvc placement. most of the techniques require equipment such as fluoroscopy (3), electrocardiography (4), or invasive pressure monitoring (5), which may not be available in all hospitals. misplacement of cvc is often diagnosed on post procedure chest x-ray (cxr) (6, 7). confirmation of cvc placement with cxr is time-consuming and will expose the patient to radiation (8, 9). saline flush test is another way for detection of cvc misplacement (10). rath et al. showed that saline flush test had 100% sensitivity and specificity to detect misplacement of subclavian vein catheter into ipsilateral internal jugular vein (11). while weekes et al. showed that rapid atrial swirl sign for subclavian and internal jugular cvc placement yielded 75% sensitivity and 100% specificity (12). based on above this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. esmailian et al. 2 figure 1: (a) ultrasound view of the heart in the subxiphoid window during saline flush of distal central venous catheter (cvc) port. the right atrium (ra) and right ventricle (rv ) are noted at time 0, at start of saline flush. (b) microbubbles visible within the ra (bold arrow) and leading into the rv (small arrow) during the saline flush at the 1-second mark indicating cvc tip in correct position in the svc. mentioned discrepancy, this study was designed to compare the diagnostic accuracy of saline flush with cxr in confirmation of above-the-diaphragm cvc placement. 2. methods 2.1. study design and setting this diagnostic accuracy study was conducted to compare two different methods of cvc confirmation in emergency departments of alzahra and kashani hospitals, isfahan, iran, from january 2015 to march 2016. the study was approved by the ethics committee of isfahan university of medical sciences and authors adhered to the principles introduced in declaration of helsinki during the study period. 2.2. participants adult patients in need of internal jugular or subclavian cvc in emergency department based on clinical indications such as cvp monitoring, infusion of vasoactive agents, administration of blood products, and etc. were enrolled. indication of cvc had been diagnosed by the emergency medicine specialist in charge of the patient’s treatment. patients with infection on puncture site, thrombosis of the target vein, right atrial mass, clavicle or proximal rib fractures, significant high-acuity traumatic conditions, pre-existing internal jugular catheter or indwelling subclavian device, svc syndrome, inability to obtain adequate subcostal or apical fourchamber images were excluded. 2.3. procedure: the neck and insertion region of target vein were cleaned with antiseptic solutions and isolated by sterile drapes when patient was in the supine position. an 18 gauge introducer needle was inserted at the predetermined puncture point. after aspirating free flow of venous blood, j-tipped guide wire was inserted and the introducer needle was removed. skin and subcutaneous tissue overlying the guide wire were dilated then cvc was railroaded over the guide wire 11-14 cm into the vein. a 10-ml sterile saline flush of the distal cvc port was performed simultaneously until the initiation of prospective recording of a 6-second digital video clip of either a standard subcostal or an apical four-chamber transthoracic cardiac window (figure 1) with ultrasound device (fukuda denshi uf-750xt class i). ultrasonography was performed by one emergency medicine resident who had undergone 6 hours of training by a radiologist using pictures and videos. proper placement of cvc tip was defined as seeing the saline swirl entering the right atrium within 2 seconds of starting the saline flush. the 2-second cut-off was chosen based on a previous investigation by vezzani et al. (9) that used this cut-off for seeing the entrance of agitated saline into the right atrium via echocardiography. by using contrast-enhanced echo to visualize the saline flush, they found that sensitivity and specificity of this method for detecting catheter misplacement were 96% and 93%, respectively (9), which inspired us to use this cut-off. when in doubt, saline flush was repeated during real-time monitoring of the right atrium. both onset and appearance of the turbulence were subjectively rated at the bedside by one emerthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e75 figure 2: study flowchart (consort format) gency physician. post-procedural cxrs were obtained in anterior-posterior view using a portable x ray machine. all cxrs were interpreted regarding the position of cvc tip and probable complications such as hemothorax, pneumothorax or pneumo-mediastinum, by the in-charge emergency medicine specialist. then, chest computed tomography (ct) was performed, as the gold standard test, in order to confirm cvc placement in all cases. chest cts were interpreted by another emergency medicine specialist who was blinded to the patients’ data. all cxr and chest ct interpretations were double checked by a radiologist. 2.4. data analysis statistical analysis was performed using spss version 21 and stata 11 software and data were reported as mean ± standard deviation or frequency and percentage. paired samples t test was used to compare the mean duration of saline flush and cxr methods for cvc confirmation. sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios as well as area under the roc curve were calculated for each method considering ct scan as the reference test and using vassarstats medical calculator. area under the roc curves of the two methods was compared using chi-square test. all data were presented with 95% confidence intervals and two-tailed p<0.05 was considered significant. accuracy of 0.90-0.100 was considered as excellent, 0.80-0.90 as good, 0.70-0.80 as fair, 0.60-0.70 as poor, and 0.50-.60 as fail. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. esmailian et al. 4 table 1: screening performance characteristics of saline flush and chest x-ray (cxr) in confirmation of central venous catheter placement characteristics saline flash cxr true positive 4 3 true negative 98 98 false positive 0 0 false negative 1 2 sensitivity 80 (29.87 98.94) 60 (17.04 92.74) specificity 100 (95.29 100) 100 (95.29 100) positive predictive value 100 (30.99 100) 100 (30.99 100) negative predictive value 98.98 (93.69 99.94) 98 (92.26 99.65) positive likelihood ratio infinity (nan infinity) infinity (nan infinity) negative likelihood ratio 0.01 (0.001 0.07) 0.02 (0.005 0.08) data were presented with 95% confidence interval; nan: calculation cannot be performed because the values entered include one or more instances of zero. figure 3: the area under the receiver operating characteristic (roc) curves of saline flush and chest x-ray (cxr) in confirmation of central venous catheter (cvc) placement (p = 0.317). 3. results 3.1. baseline characteristics 103 cases of cvc were studied (95.1% jugular vein and 4.9% subclavian vein). study flowchart is shown in figure 2. the mean age of studied patients was 57.18 ± 9.3 (35 -80) years (52.4% male). the mean duration of procedure was 2.5±1.24 minutes in saline flush method and 32.11±5.52 minutes in cxr method (p<0.001(. serious complications such as hemothorax and pneumothorax were not observed in any cases. 3.2. accuracy of methods in ct scan, 5 (4.9%) patients had cvc misplacement (3 cases of internal jugular approach and 2 cases of subclavian approach). saline flush method confirmed 4 of the 5 (80%) mentioned cases and cxr confirmed 3 of the 5 (60%) misplacement cases. table 1 and figure 3 compare the screening performance characteristics of the two methods considering the ct scan findings as the standard. the area under the roc curves for saline method and cxr in confirmation of cvc placement were 0.90 (95%ci: 0.70 0.100) and 0.80 (95%ci: 0.55 0.100), respectively (p = 0.317). 4. discussion based on the findings of the present study, the overall accuracies of saline flush and cxr in cvc placement confirmation were in the same range (good: 0.80-0.90). however, saline flush method took significantly less time and had a higher specificity in this regard. therefore, it seems that saline flush method could be considered as a safe, rapid, and accurate bedside method of cvc placement confirmation in emergency department. in gekle r et al. study the mean confirmation time of cvc placement was 8.80 minutes with ultrasonography and 45.78 minutes with cxr (13). moreover, duran-gehring pe et al. showed the mean total ultrasonography time was 5.0 minutes compared to 28.2 minutes for cxr (14). maury et al. showed the mentioned times to be 6.8±3.5 and 80.3±66.7 minutes, respectively (8). all of these results are in line with our findings. on the other hand, studies have clarified that cxr is associated with radiation exposure and additional costs (8, 9). however, using ultrasonography for confirmation of cvc placement has some limitations, including being dependent on operator performance. in evaluation of 83 cvc placements with ultrasonography, matsushima and frankel showed its poor sensitivity (50%) (15). weekes et al. (12) compared contrast-enhanced ultrasonography alone with cxr for confirmation of proper catheter tip placement in 135 emergency department patients, and reported 75% sensitivity and 100% specificity for this method. it has been suggested that performing cxr is not necessary when cvc placement is uncomplicated (16, 17). in one study it was concluded that when right internal jugular cvc placement was uncomplicated cxr could be safely skipped (18). therefore, according to proven benefits of saline flush this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e75 tests in detecting cvc placement compared to cxr (lower time, higher sensitivity, radiation free), it is a more effective method. however, saline flush test requires equipment such as ultrasonography and a person who is expert in performing the test. therefore, teaching this method to emergency physicians should be considered in educational courses. 5. limitation since the studied patients were all critically ill, all the cxrs have been performed in the anterior-posterior view, which can affect its accuracy. duration of training for the ultrasonography performer and his/her skill in interpretation and performing ultrasonography are also among other limitations that can affect the accuracy of this method to a great extent. 6. conclusion based on the findings of the present study, the overall accuracies of saline flush and cxr in cvc placement conformation were in same range (good: 0.80-0.90) without any significant difference. however, saline flush method took significantly less time and had higher specificity in this regard. therefore, it seems that saline flush method could be considered as a safe, rapid, and accurate bedside method of cvc placement confirmation in emergency department. 7. appendix 7.1. acknowledgements we gratefully acknowledge the dedicated efforts of the investigators, the coordinators, the volunteer patients who participated in this study, and the clinical research development units (crdu) of isfahan alzahra hospital. 7.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support this study was financially supported by isfahan university of medical sciences. 7.4. conflict of interest the authors have indicated that they have no conflict of interest regarding the content of this article. references 1. schummer w, schummer c, rose n, niesen w-d, sakka sg. mechanical complications and malpositions of central venous cannulations by experienced operators. intensive care medicine. 2007;33(6):1055-9. 2. walshe c, phelan d, bourke j, buggy d. vascular erosion by central venous catheters used for total parenteral nutrition. intensive care medicine. 2007;33(3):534-7. 3. boardman p, hughes j. pictorial review: radiological evaluation and management of malfunctioning central venous catheters. clinical radiology. 1998;53(1):10-6. 4. starr ds, cornicelli s. ekg guided placement of subclavian cvp catheters using j-wire. annals of surgery. 1986;204(6):673. 5. ambesh sp, pandey jc, dubey pk. internal jugular vein occlusion test for rapid diagnosis of misplaced subclavian vein catheter into the internal jugular vein. the journal of the american society of anesthesiologists. 2001;95(6):1377-9. 6. bowdle a. vascular complications of central venous catheter placement: evidence-based methods for prevention and treatment. journal of cardiothoracic and vascular anesthesia. 2014;28(2):358-68. 7. costello jm, clapper tc, wypij d. minimizing complications associated with percutaneous central venous catheter placement in children: recent advances. pediatric critical care medicine. 2013;14(3):273-83. 8. maury e, guglielminotti j, alzieu m, guidet b, offenstadt g. ultrasonic examination: an alternative to chest radiography after central venous catheter insertion? american journal of respiratory and critical care medicine. 2001;164(3):403-5. 9. vezzani a, brusasco c, palermo s, launo c, mergoni m, corradi f. ultrasound localization of central vein catheter and detection of postprocedural pneumothorax: an alternative to chest radiography. critical care medicine. 2010;38(2):533-8. 10. toshniwal gr, rath gp, bithal pk. flush test–a new technique to assess the malposition of subclavian central venous catheter position in the internal jugular vein. journal of neurosurgical anesthesiology. 2006;18(4):2689. 11. rath g, bithal p, toshniwal g, prabhakar h, dash h. saline flush test for bedside detection of misplaced subclavian vein catheter into ipsilateral internal jugular vein. british journal of anaesthesia. 2009;102(4):499-502. 12. weekes aj, johnson da, keller sm, efune b, carey c, rozario nl, et al. central vascular catheter placement evaluation using saline flush and bedside echocardiography. academic emergency medicine. 2014;21(1):65-72. 13. gekle r, dubensky l, haddad s, catlin t, stickles s, d’amore j, et al. can bedside sonography replace conventional radiography for confirmation of above-thediaphragm central venous catheter placement? annals of emergency medicine. 2013;62(4):s34-s5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. esmailian et al. 6 14. duran-gehring pe, guirgis fw, mckee kc, goggans s, tran h, kalynych cj, et al. the bubble study: ultrasound confirmation of central venous catheter placement. the american journal of emergency medicine. 2015;33(3):315-9. 15. matsushima k, frankel hl. detection of central venous catheter insertion-related complication using bedside ultrasound: the cvc sono. journal of trauma and acute care surgery. 2011;70(6):1561-3. 16. puls le, twedt ca, hunter je, langan em, crane m. confirmatory chest radiographs after central line placement: are they warranted? southern medical journal. 2003;96(11):1138-42. 17. sanabria a, henao c, bonilla r, castrillon c, cruz h, ramirez w, et al. routine chest roentgenogram after central venous catheter insertion is not always necessary. the american journal of surgery. 2003;186(1):35-9. 18. lessnau k-d. is chest radiography necessary after uncomplicated insertion of a triple-lumen catheter in the right internal jugular vein, using the anterior approach? chest. 2005;127(1):220-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction archives of academic emergency medicine. 2023; 11(1): e3 editorial analysis of articles in the journal of archives of academic emergency medicine in 2022 somayeh saghaei dehkordi1∗, mehrnoosh yazdanbakhsh1 1. journal office, emergency ward, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: november 2022; accepted: december 2022; published online: 1 january 2023 cite this article as: saghaei dehkordi s, yazdanbakhsh m. analysis of articles in the journal of archives of academic emergency medicine in 2022. arch acad emerg med. 2023; 11(1): e3. https://doi.org/10.22037/aaem.v11i1.1882. in 2022, archives of academic emergency medicine (aaem) has published 90 articles, all of which are indexed by scopus, web of sciences, pubmed and some other databases. they have been authored by more than four hundred researchers from various countries, including but not limited to the united states, japan, korea, canada, ghana, france, norway, india, china, thailand, malaysia, pakistan, greece, viet nam and iran. in this editorial, we intend to provide an overview of the journal’s flow in 2022, like we did in 2021 (1), so that we can identify our strengths and weaknesses and provide a brief report on our performance to readers and authors, which they might find useful in becoming more familiar with the journal. this article could help the authors who are interested in publishing with us to become more familiar with the journal’s aim and scope, and also the editorial priorities and preferences. the scopus citescore for the journal improved from 4.5 in 2021 to 5.5 (as calculated in november 2022) (https://www.scopus.com/sourceid/21101017909?origin=re sultslist). aaem has been ranked as a q1 journal in the field of emergency medicine in 2021 with an sjr of 0.651 based on the ranking published on scimagojr website (reported in 2022). https://www.scimagojr.com/journalrank.php?area=2700&ca tegory=2711. aaem is indexed in the ici journals master list database, has positively passed the evaluation process for 2021, and received an icv of 125.25 (reported in 2022). of all the submitted articles in 2022, 30.03% were published and 69.97% were rejected (61.27% of the submitted articles were desk rejected, 8.41% were declined after peer review, and rate of rejection due to other reasons was 0.29%) (table ∗corresponding author: somayeh saghaei dehkordi; emergency ward, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. email: ma.saghaei63@gmail.com, tel: +982122721155, orcid: https://orcid.org/0000-0003-0954-5202. 1). average days to acceptance was 75 and average days to rejection was 11. all articles that passed the initial evaluation were reviewed by two or three referees and more than 300 reviewers helped us improve the quality of the articles published by the journal through reviewing the articles. we appreciate their contribution and would like to thank them here. out of the 90 published papers, 50 (55.55%) were original articles, 17 (18.9%) were review articles, 10 (11.11%) were case reports, 2 (2.22%) were photo quizzes, 5 (5.55%) were brief reports, and 6 (6.66%) were letters to editor (including one editorial). despite the reduction of covid-19 incidence, researches were still conducted on issues related to this disease, for example, checking the results of vaccination, vaccines & booster doses and summarizing the results. we also played our role by publishing relevant and useful articles that we believed could help health care systems and present valuable findings from iran to the world. 16 articles were original research papers (2-17) and 5 articles were review papers (1822). among original articles, 13 articles were published on the topic of emergency medicine, which were aimed at planning and improving the quality of service delivery (6, 14, 23-33). there were 5 clinical trials among the published original articles, which dealt with issues such as treatment of acute migraine headache (34, 35), impact of 3% hypertonic saline on electrocardiogram changes due to tramadol poisoning (36), ethanol sclerotherapy in the management of ovarian endometrioma (37), and aromatherapy (38). among the case reports, 2 were on possible complications arising after treatments (39, 40) and 8 reported unusual presentations of diseases (41-48). two letters were published on monkeypox (49, 50) and one letter was written in response to an article previously published in the journal (51). we believe that publishing articles in response to previous articles can help raise the awareness this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. saghaei dehkordi et al. 2 table 1: comparison of articles in 2022 with total articles 2022 year (%) total (%) submissions accepted 30.03 41.89 submissions declined 69.97 58.11 desk-rejected 61.27 35.14 declined (post-review) 8.41 17.54 other reasons 0.29 5.43 of our audience and help them be more careful when conducting research in the future, and we welcome such articles. the journal team strives to provide useful and valuable research results of doctors and researchers to be a resource for doctors and researchers who can improve the public health of all societies. therefore, we would like to thank all the authors who trusted us and provided us with their valuable manuscripts throughout 2022. our goal is to continue to improve and continue to publish quality articles from authors around the world, and everyone is invited to join us. references 1. yazdanbakhsh m, saghaei dehkordi s. an overview of published articles in archives of academic emergency medicine in 2021. archives of academic emergency medicine. 2022;10(1):e18. 2. zare dehnavi a, salehi m, arab ahmadi m, asgardoon mh, ashrafi f, ahmadinejad n, et al. clinical, laboratory and imaging characteristics of hospitalized covid-19 patients with neurologic involvement; a cross-sectional study. archives of academic emergency medicine. 2022;10(1):e10. 3. maher a, dehnavi h, salehian e, omidi m, hannani k. relationship between income level and hospitalization rate in covid-19 cases; an example of social factors affecting health. archives of academic emergency medicine. 2022;10(1):e23. 4. singh a, soni kd, singh y, aggarwal r, venkateswaran v, ashar ms, et al. alveolar arterial gradient and respiratory index in predicting the outcome of covid-19 patients; a retrospective cross-sectional study. archives of academic emergency medicine. 2022;10(1):e28. 5. khari s, salimi akin abadi a, pazokian m, yousefifard m. curb-65, qsofa, and sirs criteria in predicting inhospital mortality of critically ill covid-19 patients; a prognostic accuracy study. archives of academic emergency medicine. 2022;10(1):e36. 6. ansari djafari a, javanmard b, rahavian a, rafiezadeh arr, borumandnia n, hojjati sa, et al. impact of covid19 pandemic on emergency department referrals with urologic complaints; a retrospective cross-sectional study. archives of academic emergency medicine. 2022;10(1):e37. 7. tavakolian a, ashrafi shahri sh, jafari ma, pishbin e, zamani moghaddam h, foroughian m, et al. an 18month epidemiologic survey of 3364 deceased covid19 cases; a retrospective cross-sectional study. archives of academic emergency medicine. 2022;10(1):e42. 8. rayegani sm, bozorgmehr r, angooti oshnari l, mahdi kaghazi ah. the effect of exercise-based pulmonary rehabilitation on quality of life in recovered covid-19 patients; a quasi-experimental study. archives of academic emergency medicine. 2022;10(1):e45. 9. bozorgmehr r, amiri f, hosein zade m, ghorbani f, khameneh bagheri a, yazdi e, et al. effect of sofosbuvir on length of hospital stay in moderate covid-19 cases; a randomized controlled trial. archives of academic emergency medicine. 2022;10(1):e46. 10. haji aghajani m, miri r, sistanizad m, toloui a, madani neishaboori a, pourhoseingholi a, et al. risk factors of readmission in covid-19 patients; a retrospective 6month cohort study. archives of academic emergency medicine. 2022;10(1):e48. 11. mohammadi z, faghih dinevari m, vahed n, ebrahimi bakhtavar h, rahmani f. clinical and laboratory predictors of covid-19-related in-hospital mortality; a crosssectional study of 1000 cases. archives of academic emergency medicine. 2022;10(1):e49. 12. sistanizad m, haji aghajani m, haghighi m, amini h, pourhoseingholi a, taherpour n, et al. comparing the characteristics of mucormycosis between cases with and without covid-19; a cross-sectional study. archives of academic emergency medicine. 2022;10(1):e56. 13. alizadeh n, tabatabaei f-s, azimi a, faraji n, akbarpour s, dianatkhah m, et al. lactate dehydrogenase to albumin ratio as a predictive factor of covid-19 patients’ outcome; a cross-sectional study. archives of academic emergency medicine. 2022;10(1):e63. 14. huabbangyang t, klaiangthong r, prasittichok k, koikhunthod s, wanna j, sudajun n, et al. comparing emergency medical services processing times for stroke patients before and during covid-19 pandemic; a cross-sectional study. archives of academic emergency medicine. 2022;10(1):e65. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e3 15. samimiardestani s, irani s, hasibi m, seyedahadi m, bastaninejad s, firouzifar m, et al. distinguishing characteristics of covid-19-associated mucormycosis; a case series. archives of academic emergency medicine. 2022;10(1):e66. 16. heydari f, zamani m, masoumi b, majidinejad s, nasresfahani m, abbasi s, et al. physiologic scoring systems in predicting the covid-19 patients’ one-month mortality; a prognostic accuracy study. archives of academic emergency medicine. 2022;10(1):e83. 17. mosallami aghili sm, khoshfetrat m, asgari a, arefizadeh r, mohsenizadeh a, mousavi sh. association of echocardiographic findings with in-hospital mortality of covid-19 patients and their changes in one-month follow-up; a cohort study. archives of academic emergency 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mohssenipour m, saeidi s, habibi p, dashti m, nazarian n, et al. complications of covid-19 vaccines during pregnancy; a systematic review. archives of academic emergency medicine. 2022;10(1):e76. 23. asadabadi l, soltani nejad k, zolfagharnasab a, mobasher m. proposing an emergency medicine ethical guideline; a qualitative study. archives of academic emergency medicine. 2022;10(1):e1. 24. katsomboon k, sindhu s, utriyaprasit k, viwatwongkasem c. factors associated with 24-hour clinical outcome of emergency patients; a cohort study. archives of academic emergency medicine. 2022;10(1):e30. 25. rosenow c, aguirre s, polveroni t, ginsberg z, pollock j, traub s, et al. resident productivity in the emergency department after implementation of an automated patient assignment system; a brief report. archives of academic emergency medicine. 2022;10(1):e33. 26. pouraghaei m, babaie j, rad saeed l. the challenges of emergency medical services response to arasbaran twin earthquakes; a content 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metoclopramide in symptom management of acute migraine headache; a double-blind randomized clinical trial. archives of academic emergency medicine. 2022;10(1):e19. 35. farahmand rad r, zolfaghari sadrabad a, jafari m, ghilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. saghaei dehkordi et al. 4 ian m. efficacy of sumatriptan/placebo versus sumatriptan/propofol combination in acute migraine; a randomized clinical trial. archives of academic emergency medicine. 2022;10(1):e27. 36. omraninava a, mehdizade a, karimi e, ghabousian a. potential impact of 3% hypertonic saline infusion on tramadol poisoning-induced electrocardiogram changes; a randomized clinical trial. archives of academic emergency medicine. 2022;10(1):e26. 37. ghasemi tehrani h, tavakoli r, hashemi m, haghighat s. ethanol sclerotherapy versus laparoscopic surgery in 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bagherzadeh aa, zandbaf t. jejunal dieulafoy’s lesion as a rare cause of massive gastrointestinal bleeding; a case report and literature review. archives of academic emergency medicine. 2022;10(1):e61. 47. yamashita k, hongo t, nojima t, yumoto t, nakao a, naito h. hamman’s syndrome accompanied by diabetic ketoacidosis; a case report. archives of academic emergency medicine. 2022;10(1):e68. 48. abed e, saeed o, abd el-hamid b, elsayed m, dawoud h, heikal n, et al. acute intermittent porphyria as a rare challenging neuro-metabolic disease; a case report. archives of academic emergency medicine. 2022;10(1):e74. 49. alavi-moghaddam m. monkeypox outbreak in nonendemic areas: will it cause a new pandemic? a letter to editor. archives of academic emergency medicine. 2022;10(1):e60. 50. asadollahzadeh e, ghadiri f, ebadi z, naser moghadasi a. is monkeypox a concern in multiple sclerosis patients? a letter to editor. archives of academic emergency medicine. 2022;10(1):e67. 51. megarbane b, gouda as. intravenous lipid emulsion for treating tramadol-induced seizures: surprising but worth considering for future studies; a letter to editor. archives of academic emergency medicine. 2022;10(1):e14. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index references archives of academic emergency medicine. 2023; 11(1): e51 or i g i n a l re s e a rc h periosteal nerve block vs. intravenous morphine in pain relief of distal radius and ulna fracture; a double-blind randomized clinical trial shadi ashtari1, alireza hasanzadeh1, alireza bahmani2, ali abdolrazaghnejad2,3∗ 1. medical school, tehran university of medical sciences, tehran, iran. 2. department of emergency medicine, khatam-al-anbia hospital, zahedan university of medical sciences, zahedan, iran. 3. infectious diseases and tropical medicine research center, research institute of cellular and molecular sciences in infectious diseases, zahedan university of medical sciences, zahedan, iran. received: may 2023; accepted: june 2023; published online: 23 july 2023 abstract: introduction: distal forearm fractures’ realignment and fixation is a painful procedure. this study aimed to compare the efficacy of periosteal nerve block and intravenous morphine in distal radius and ulna fractures’ pain management. methods: in the present randomized, parallel, double-blind, controlled clinical trial, patients with distal radius or ulna fractures were divided into two groups. in the first group, for periosteal nerve block, 1% lidocaine was injected at a distance of 6 to 8 cm near the wrist from the lateral radius and medial ulna. in the second group, morphine sulfate at a dose of 0.1 mg/kg was slowly injected through the peripheral vein within 5 minutes. the visual analog scale (vas) score was evaluated before the intervention and every 15 minutes until 90 minutes after the intervention and was compared between the two groups. results: 75 subjects were studied (39 in the periosteal nerve block and 36 in the intravenous morphine group). there were no significant differences between the groups in terms of mean age (p = 0.384), gender distribution (p = 0.464), past medical history (p = 0.106), trauma type (p = 0.836), fracture type (p = 0.613), and baseline pain severity on vas (p = 0.987). both methods reduced the vas scores during the 90 minutes of the study. the mean pain scores of the patients in the periosteal nerve block group with 2.56±1.44, 2.15±1.11, 2.66±1.26, and 3±1.27 at 15, 30, 45, and 60 minutes after the analgesic injection, respectively, were significantly lower than those of the intravenous morphine group with 4.75±1.27, 4.22±1.22, 3.97±1.27, and 4.13±1.35, respectively (p < 0.001 for all comparisons). in the present study, no local or systemic complications were observed in the periosteal nerve block group, while the complications of dyspnea, vomiting, and pruritus were reported by 5.5%, 2.8%, and 2.8%, respectively, in the intravenous morphine group. moreover, the percentage of need for additional analgesia in the intravenous morphine group was higher than that of the periosteal nerve block group. conclusion: in the first hour after the intervention, pain reduction in periosteal block was significantly higher than intravenous morphine administration. also, the incidence of complications and the need for additional analgesia were lower in the periosteal block group compared to intravenous morphine administration. keywords: wrist fractures; pain; visual analog scale; nerve block; morphine cite this article as: ashtari s, hasanzadeh a, bahmani a, abdolrazaghnejad a. periosteal nerve block vs. intravenous morphine in pain relief of distal radius and ulna fracture; a double-blind randomized clinical trial. arch acad emerg med. 2023; 11(1): e51. https://doi.org/10.22037/aaem.v11i1.2056. ∗corresponding author: ali abdolrazaghnejad; department of emergency medicine, khatam-al-anbia hospital, zahedan university of medical sciences, zahedan, iran. email: ali.abdolrazaghnejad@zaums.ac.ir, orcid: https://orcid.org/0000-0002-4121-1643. 1. introduction forearm fractures account for up to 44% of total bone fractures and affect almost the entire age range of the population (1). in approximately 20% of cases, more commonly in elderly ones, the treatment requires hospitalization and invasive surgical procedures (2). the primary approach to this fracture is a crucial determinant of the need for surgery and further hospitalization. most of these patients need maniputhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. ashtari et al. 2 lation, usually consisting of bone realignment and fixation, in the emergency departments (eds) (3). to perform the manipulation, patients must be anesthetized. different systemic and local anesthesia techniques have been applied to reduce pain in these patients. the most common methods employed for manipulating these fractures include, but are not limited to, using intravenous morphine sulfate (for systemic anesthesia) and the hematoma block, the bier block, and the brachial plexus block (for local anesthesia). all these methods have their advantages and disadvantages. in distal forearm fractures, the local anesthetics could spread out into the volar periosteum, because of the fracture’s location, and consequently reduce the efficacy of the hematoma block (4). furthermore, there is the risk of adverse events due to the diffusion of the regional drugs into the circulatory system, both in the hematoma and bier blocks. these complications include arrhythmia, hypotension, and central nervous system (cns) complications such as tinnitus, confusion, drowsiness, and seizure (5). also, the brachial plexus block requires hospitalization and skilled practitioners, making this method infrequent. there is no consensus on the most efficient method for manipulating distal radius and ulna fractures (6-9). on the other hand, the periosteal nerve block is a recent method that seems to have fewer complications due to the site of injection and the procedural method, which results in a less unpleasant vascular and systemic involvement. it has also been hypothesized that it might better reduce the pain as this method is performed closer to the nerve origin. tageldin et al. conducted a clinical study on the effects of the periosteal nerve block on the pain intensity and the success rate of manipulating the closed distal radius and ulna fractures. they showed that this method could yield promising results and be effective in these patients (10). in fact, a complicated sensory and autonomic nerve supply is present in bones. the nutrient arteries are accompanied with nerves within the perivascular spaces inside the haversian systems and provide osteocytes with polypeptides, which contribute to regulate the osteoblastic and osteoclastic activity. however, it must be noted that proposing the precise location for applying the anesthesia could be challenging due to the lack of knowledge about the exact mechanism of periosteal pain sensation. based on the above-mentioned points, the current study aimed to compare the efficacy of periosteal nerve block and intravenous morphine in distal radius and ulna fractures’ pain management. 2. methods 2.1. study design and setting the present study was a randomized, parallel, double-blind, controlled clinical trial conducted from 2018 to 2019 in sina hospital to compare the efficacy and complications of the two mentioned methods in distal radius and ulna fractures’ pain management. this trial was in concordance with the declaration of helsinki and its later amendments. the ethics committee of tehran university of medical sciences approved this trial (ir.tums.medicine.rec.1396.2838), and all patients provided informed consent before entering the study. this study was registered in the iranian registry of clinical trials (registry code: irct20131203015640n6). 2.2. participants we included patients older than 18 years old with closed distal radius or ulna fractures who needed manipulation in ed. the exclusion criteria were open fractures or fractures associated with evidence of neurovascular damage or compartment syndrome, patients with head or multiple trauma, patients with the loss of consciousness, and patients with contraindication for lidocaine or morphine use. 2.3. data gathering at the beginning of the study, the primary demographic and clinical data (age, gender, and the fracture site) were recorded. a visual analog scale (vas) was used to estimate the amount of pain during the trial. the vas score is a broadly used instrument that consists of a 10-cm ruler extending longitudinally between zero to ten, with zero indicating no pain or discomfort and ten indicating pain too intense to be tolerated. patients were asked to mark their inconvenience on this ruler. we recorded vas just before the injection and at 15, 30, 45, 60, 75, and 90 minutes after the injection in both groups. the diagnosis by the emergency medicine specialist was based on the clinical examination and radiological findings (anterior and lateral x-ray images of the distal forearm). these patients were classified, based on the guidelines of american society of anesthesiologists, either as class-i (normal healthy patients) or class-ii (patients with mild systemic disease). 2.4. randomization and blinding the participants were equally randomized into two groups in a 1:1 ratio. the randomization method was based on permuted block randomization with block sizes of four. in addition, lidocaine and distilled water were prepared in 10cc syringes and labeled b1 and b2 before the intervention in order to comply with blinding conditions. moreover, morphine sulfate with the dose of 0.1mg was diluted with distilled water in 5cc syringes such that each cc contained 1mg of morphine (5mg in total). other 5cc syringes containing placebo were prepared and coded with labels m1 and m2. then, a 10cc syringe containing lidocaine (b1) and a 5cc syringe containing distilled water (m1) were placed in 46 enthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e51 velopes (as the periosteal nerve block group). furthermore, a 10cc syringe containing distilled water (b2) and a a 5cc syringe containing placebo (m2) were placed in the other 46 envelopes (as the intravenous morphine group). the envelopes were provided to the emergency medicine specialist daily to administer 10cc syringes in the periosteal nerve and 5cc syringes intravenously. thus, the interventionist, the patient, the evaluator, and the statistical analyst had no knowledge of the type of intervention in each group until the end of the study. 2.5. intervention to perform periosteal nerve block, an injection was performed in the first intervention group using a 10cc syringe with a 22-gauge needle containing 1% lidocaine at a distance of 6-8 cm proximal to the wrist from the lateral radius and medial ulna. in this group, 5cc of distilled water was injected intravenously as placebo instead of morphin. it is necessary to mention that the periosteal nerve block was performed in the same way as described in tagelbin et al.’s study (10). the patients were positioned supine on the procedural table with the affected hand on a pillow placed on the dressing table, which was considered to cause the least vascular or neurological complications. afterward, the 22-gauge needle was directed towards the radius at a right angle until the needle tip leaned on the lateral aspect of the radius. then, lidocaine solution was injected centrally, slightly anteriorly, and posteriorly to cover the entire lateral surface of the radius. next, the needle was withdrawn and replaced by another needle at the same entry point. after touching the bone, the injection continued side to side with radius by inserting 0.5 ml of lidocaine solution for every 0.5 cm advancement of the needle. this process continued until the bone could no longer be felt with the needle tip. after withdrawing the needle, the skin was rotated posteriorly, and the needle tip was inserted towards the dorsal surfaceby using the same entry point. the mentioned procedure was repeated for the ventral side. moreover, this nerve block protocol was also performed for ulnar fracture in the same way (figure 1). in the second intervention group, morphine sulfate was calculated at the dose of 0.1mg per kilogram of body weight and diluted with distilled water in pre-prepared syringes such that each cc contained 1mg of morphine. this amount was slowly infused through the peripheral vein within 5 minutes. block operation was also done using distilled water. the manipulation procedure was performed 15 minutes after performing periosteal nerve block or intravenous morphine injection. it should be noted that in both methods, if the patient’s pain score did not reach less than 5 within 30 minutes after the intervention, fentanyl at the dose of 1mcg/kg after dilution with 5cc of distilled water was administered intravenously as the additional analgesia. 2.6. outcomes change in pain severity at 15, 30, 45, 60, 75, and 90 minutes after the injection (based on vas score) and systemic or local complications were considered as outcomes of this study. 2.7. statistical analysis the sample size was estimated to be 46 patients in each group, considering the confidence level of 95% and the test power of 80%, as well as the assumption of equal variance of pain in the two groups, and the mean difference of pain equal to 0.6. the statistical package of social science software (spss inc., chicago, il, usa) was used to compare the two study groups. continuous variables were represented using mean and standard deviation, while categorical variables were demonstrated as frequency and percentage. a chi-squared test was performed to evaluate the differences between categorical parameters. considering the result of the kolmogorovsmironov test indicating the normal distribution of data, univariate analysis was used to compare the mean pain score between the two groups by adjusting need for additional analgesia. moreover, independent samples t-test was used to compare other quantitative variables between the two groups. the significance level of p-value less than 0.05 was considered in all analyses. 3. results 3.1. baseline characteristics of studied cases from a total of 92 patients, 17 subjects were excluded due to patients’ refusal to continue the trial, and finally 75 subjects, including 39 patients in the periosteal nerve block group and 36 patients in the intravenous morphine group, remained for the final analysis (figure 2). the periosteal nerve block group comprised 9 (23.1%) female and 30 (76.9%) male patients with the mean age of 35.53±17.13 years, and the intravenous morphine group consisted of 11 (30.6%) females and 25 (69.4%) males with the mean age of 36.22±13,71 years. table 1 compares the baseline characteristics of studied cases between groups. there were no significant differences between the groups in terms of mean age (p = 0.384), gender distribution (p = 0.464), past medical history (p = 0.106), trauma type (p = 0.836), fracture type (p = 0.613), and baseline pain severity on vas (p = 0.987). 3.2. comparing the outcomes pain management table 2 and figure 3 compare the vas scores between groups 15, 30, 45, and 60 minutes after the intervention. both methods reduced the vas scores during the 90 minutes of the study. the mean pain scores of the patients in the periosteal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. ashtari et al. 4 nerve block group with 2.56±1.44, 2.15±1.11, 2.66±1.26, and 3±1.27 at 15, 30, 45, and 60 minutes after the analgesic injection, respectively, were significantly lower than those of the intravenous morphine group with 4.75±1.27, 4.22±1.22, 3.97±1.27, and 4.13±1.35, respectively (p < 0.001 for all comparisons). however, this difference became insignificant 75 (p = 0.062) and 90 (p = 0.138) minutes after the intervention. as shown in figure 3, these analgesic effects were attenuated over time. it should also be noted that the slightest pain perception was reported 30 minutes after the intervention in the periosteal nerve block group and 45 minutes after the intervention in the intravenous morphine group; thus, these were probably the best times for performing the reduction. complications in the present study, no local or systemic complications were observed in the periosteal nerve block group, while dyspnea, vomiting, and pruritus were reported by 5.5%, 2.8%, and 2.8%, respectively, in the intravenous morphine group. moreover, the percentage of need for additional analgesia in the intravenous morphine group was higher than that of the periosteal nerve block group. these differences were at a statistically borderline significance (table 2). 4. discussion the results of the present study showed that from fifteen minutes after the intervention, the periosteal nerve block method was more effective than intravenous morphine administration in reducing patients’ pain. in this regard, frenkel et al. (2011) reported an 18-year-old woman referring to the ed with an angular fracture towards the dorsal and distal radius (colles’s fracture). as the alternative sedation procedure, the supra-condylar block of the radial nerve (proximal to its branching position) was performed under ultrasonography guidance. the procedural pain was minimal, and the result of manipulation was successful (11). it should be noted that ultrasound was not used to accurately reach the injection site for injecting lidocaine in the periosteal nerve around the radius and ulnar bone in the present study. one reason for the limited use of local anesthesia in the treatment of forearm fractures is concerns about its effectiveness and the degree of sedation during manipulation (12). different methods such as hematoma block, bier block, and cubital nerve block are used for local analgesia in ractures. some studies have reported the effectiveness of the bier block, as compared to the hematoma block, in pain relief (13-15), even though the problems associated with bier block included more extended preparation and administration time. the periosteal nerve block is a relatively new method to overcome the pain induced by fracture and manipulation. for the first time, tageldin et al.’s (2015) study on 42 patients with closed distal fractures and ulna fractures under periosteal nerve block with 1% lidocaine showed that the reduction procedure was painless in 35 patients (83%) (vas = 0) and had minor pain in 6 patients (14%) (vas = 1-3). in the age range of 12 to 16 years, the reduction procedure was painless in 15 (94%) patients, and the pain was mild in 1 patient. forty patients who had a successful manipulation procedure with a periosteal nerve block did not require any other method of analgesia. moreover, the periosteal nerve block group showed no local or systemic complications (10). similar to the above-presented study, there were no complications in the periosteal nerve block group in our study, and the complication rate of only 11.1% was reported in the intravenous morphine group. furthermore, 2.6% and 16.7% of patients in the periosteal nerve block group and the intravenous morphine group, respectively, needed an additional analgesia. however, this difference was at a statistically borderline significance. in the most recent study, published in 2021, on pain management with periosteal nerve block for reducing distal radius fracture, as mentioned in the results, the periosteal nerve block was found to be an effective method providing satisfactory analgesia to reduce pain in distal radial and ulnar fractures. it had no complications and was free from complications associated with the conventional sedation method (16). in a case report by ahmad et al. (2017), a 46-year-old man with ulna fracture after a motorcycle accident underwent periosteal nerve block with lidocaine, after which, the treatment of the fracture was started. it was found that this method reduced the pain in the patient, did not need any additional analgesia, and had no reports of local and systemic complications (17). the most commonly used drug in local anesthesia is lidocaine, which was also used in this study. in a study by shaik et al. (18), the effect of butorphanol was evaluated as an adjuvant treatment with lidocaine in periosteal nerve block and hematoma block. according to the hypothesis of this study, pain-bearing peripheral nerves contain opioid receptors, and the block of these receptors during hematoma block or a periosteal nerve block can provide better analgesia. one hundred-fifteen patients with closed fractures were randomly assigned to two groups as follows: the first group as the periosteal nerve block group received only lidocaine 1% (2mg /kg), and the second group received lidocaine 1% (2mg/kg) and also butorphanol (0.02mg/kg). after performing the block procedure, the amount of pain was measured before, during, and after the manipulation using the vas score. the results revealed that the onset time of anesthesia was significantly lower in the patients receiving the combination therapy, compared to those reveiving only lidocaine. besides, the need for additional analgesic method was signifthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e51 icantly lower in the butorphanol group, compared to the lidocaine group. the mean vas score in the butorphanol adjunction group was significantly less than that of the lidocaine only group during and after the reduction. the difference between hematoma block and periosteal nerve block in reducing the amount of pain and success of manipulation in the studied groups was not investigated. our study confirmed the findings of these published studies and showed the advantage of the periosteal nerve block concerning pain relief and adverse events. 5. strengths and limitations the small sample size was one of the most important limitations of the present study. since the periosteal nerve block is a new method, the researchers in the present study tried to get patients’ consent to participate in the study by expressing its significance and effectiveness in the possible pain reduction. in addition, although the use of adjacent saline (instead of lidocaine) near a fracture site can cause pain, the degree of this pain was not much different from that of the lidocaine injection. in general, the additional prescription of placebo or adjacent saline injection can be one of the weaknesses of this study. however, the prevention of bias and conformity to the blinding conditions in this study can be the strong points of the study. another limitation of this study was not comparing the effect of periosteal nerve block with other types of blocks such as a hematoma block/other peripheral nerve block, or procedural sedation. making such a comparison is recommended to be addressed in future studies. furthermore, lidocaine and morphine were the only drugs used in this trial. therefor, the effectiveness of lidocaine, compared with other pain relievers should be examined in future studies. finally, since periosteal nerve block was found to be a promising approach for pain relief based on these results, it is suggested to consider the mentioned limitations and conduct further prospective studies with larger sample sizes and different settings to validate the obtained results. 6. conclusion in the first hour after the intervention, pain reduction in periosteal block was significantly higher than intravenous morphine administration. also, the incidence of complications and the need for additional analgesia were lower in the periosteal block group compared to intravenous morphine administration. additional trials could help validate the obtained results and reach a more comprehensive decision on the preferred method for analgesia in distal forearm fractures. 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest the authors declare that they have no conflict of interest in this trial. 7.3. funding and support none declared. 7.4. authors’ contribution ?????????????? 7.5. using artificial intelligence chatbots none. 7.6. informed consent informed consent was obtained from all patients included in the study. references 1. chung kc, spilson sv. the frequency and epidemiology of hand and forearm fractures in the united states. j hand surg am. 2001;26(5):908-15. 2. o’neill tw, cooper c, finn jd, lunt m, purdie d, reid dm, rowe r, woolf ad, wallace wa, uk colles’ fracture study group. incidence of distal forearm fracture in british men and women. osteoporos int. 2001;12:555-8. 3. azizkhani r, hassan s, boroumand a, rastin g, ghasemi a, shahbazi a. analgesic effects of ketamine nebulizer vs. intravenous morphine in limb trauma patients in pre-hospital emergency setting; a randomized doubleblinded clinical trial. advanced journal of emergency medicine. 2020;4(4):e84. 4. s sankar b, ng ab. circumferential periosteal block in the reduction of distal radius fractures. ann r coll surg engl. 2005;87(2):141. 5. el-boghdadly k, pawa a, chin kj. local anesthetic systemic toxicity: current perspectives. local and regional anesthesia. 2018;11:35-44. 6. abdolrazaghnejad a, banaie m, tavakoli n, safdari m, rajabpour-sanati a. pain management in the emergency department: a review article on options and methods. advanced journal of emergency medicine. 2018;2(4):e45. 7. handoll hh, madhok r, dodds c. anaesthesia for treating distal radial fracture in adults. cochrane database syst rev. 2002(3):cd003320. 8. mohammadshahi a, abdolrazaghnejad a, nikzamir h, safaie a. intranasal ketamine administration for narcotic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. ashtari et al. 6 dose decrement in patients suffering from acute limb trauma in emergency department: a double-blind randomized placebo-controlled trial. advanced journal of emergency medicine. 2018;2(3):e30. 9. janati m, kariman h, memary e, davarinezhadmoghadam e, arhami-dolatabadi a. educational intervention effect on pain management quality in emergency department; a clinical audit. advanced journal of emergency medicine. 2018;2(2):e16. 10. tageldin me, alrashid m, khoriati aa, gadikoppula s, atkinson hd. periosteal nerve blocks for distal radius and ulna fracture manipulation–the technique and early results. j orthop surg res. 2015;10:134. 11. frenkel o, herring aa, fischer j, carnell j, nagdev a. supracondylar radial nerve block for treatment of distal radius fractures in the emergency department. j emerg med. 2011;41(4):386-8. 12. constantine e, steele dw, eberson c, boutis k, amanullah s, linakis jg. the use of local anesthetic techniques for closed forearm fracture reduction in children: a survey of academic pediatric emergency departments. pediatr emerg care. 2007;23(4):209-11. 13. abbaszadegan h, jonsson u. regional anesthesia preferable for colles’ fracture: controlled comparison with local anesthesia. acta orthop scand. 1990 jan 1;61(4):3489. 14. cobb ag, houghton gr. local anaesthetic infiltration versus bier’s block for colles’ fractures. bmj (clinical research ed.). 1985;291(6510):1683. 15. wardrope j, flowers m, wilson dh. comparison of local anaesthetic techniques in the reduction of colles’ fracture. emerg med j. 1985;2(2):67-72. 16. ali wa, soh ez, abdullah s, singh ps, ahmad aa, sapuan j. pain perception during the phases of manual reduction of distal end radius fracture with a periosteal block. cureus. 2021;13(1). 17. ahmad aa, ikram ma. plating of an isolated fracture of shaft of ulna under local anaesthesia and periosteal nerve block. trauma case rep. 2017;12:40-4. 18. sshaik na, rao ss, chiruvella s, rao ms, reddy sv. effectiveness of butorphanol as an adjuvant to lidocaine for haematoma or periosteal block: a prospective, randomised, double blind study. indian j anaesth. 2013;57(2):150. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e51 table 1: comparing the baseline characteristics of studied cases between periosteal nerve block and intravenous morphine groups variables groups p value nerve block (n= 39) morphine (n= 36) age (years) mean ± sd 35.53±17.13 36.22±13,71 0.384 gender female 9(23.1) 11(30.6) 0.464 male 30(76.9) 25(69.4) past medical history diabetes mellitus 3 (7.7) 2 (5.6) 1.000 hypertension 3 (7.7) 3 (8.3) 1.000 ischemic heart disease 1 (2.6) 1 (2.8) 1.000 history of surgery 0 (0.0) 3 (8.3) 0.106 type of trauma car accident 19(48.7) 20(55.6) physical fight 4(10.3) 3(8.3) 0.836 falling 16(41) 13(36.1) type of fracture distal radius 26(66.7) 20(55.6) distal ulna 4(10.3) 5(13.0) 0.614 both distal radius and ulna 9(23.1) 11(30.6) pain severity on vas mean ± sd 7.33±1.19 7.38±1.1 0.987 data are presented as mean ± standard deviation (sd) or frequency (%). vas: visual analogue scale. table 2: comparing the outcomes between periosteal nerve block and intravenous morphine groups after intervention outcomes groups p value nerve block (n= 39) morphine (n= 36) pain severity on vas before the study 7.33±1.19 7.38±1.1 0.987 15 minutes 2.56±1.44 4.75±1.27 <0.001 30 minutes 2.15±1.11 4.22±1.22 <0.001 45 minutes 2.66±1.26 3.97±1.27 <0.001 60 minutes 3±1.27 4.13±1.35 <0.001 75 minutes 3.79±1.52 4.55±1.46 0.062 90 minutes 5.05±1.57 4.61±1.47 0.138 complications dyspnea 0 (0%) 2 (5.5) vomiting 0 (0%) 1 (2.8) 0.048 pruritus 0 (0%) 1 (2.8) need for additional analgesia 1(2.6%) 6(16.7%) 0.050 data are presented as mean ± standard deviation (sd) or frequency (%). vas: visual analogue scale. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. ashtari et al. 8 figure 1: performing a periosteal nerve block as a schematic section of the distal radius or ulna of the forearm 6-8 cm proximal to the wrist joint. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e51 figure 2: flow diagram of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. ashtari et al. 10 figure 3: visual analogue scale (vas) score changes in the two groups during the trial. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion strengths and limitations conclusion declarations references emergency. 2017; 5 (1): e48 ca s e re p o rt a 5-month-old infant with right scrotum swelling; a case report shih-wen hung1,3, kuo-chih chen1,3, chin-chu wu2, tzong-luen wang1,3, aming chor-ming lin1,3∗ 1. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. department of medical imaging, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. school of medicine, fu-jen catholic university, new taipei city, taiwan. received: september 2016; accepted: september 2016; published online: 14 january 2017 abstract: migration of the distal catheters of ventriculoperitoneal (vp) shunt is a rare event. here, we report an unusual case of a 5-month-old infant with post-hemorrhagic hydrocephalus, who developed right scrotum swelling soon after vp shunting. plain abdominal x-ray showed the shunt tubing, which was twisted and kinked in its distal portion and coiled in the right scrotum. the infant was operated on and managed with successful outcome. keywords: ventriculoperitoneal shunt; equipment failure; hydrocephalus; radiography, abdominal; case reports © copyright (2017) shahid beheshti university of medical sciences cite this article as: hung sw, chen kc, wu cc, wang tl, lin ac. a 5-month-old infant with right scrotum swelling; a case report. emergency. 2017; 5 (1): e48. 1. introduction ventriculoperitoneal (vp) shunting is one of the most common pediatric neurosurgery operations performed for dealing with hydrocephalus (1). following the performance of this procedure, excess cerebrospinal fluid (csf) will be diverted from the brain ventricles to the peritoneal cavity of the abdomen via a catheter (2). however, it can be associated with numerous complications and consequences such as infection, knotting, malfunction and etc. that are reported to have a rate as high as 70% in the first year after placement and an annual occurrence rate of about 5% thereafter (2, 3). migration of the distal tube of vp shunt into several body compartments are among rare complications of vp shunting, which have been reported as case reports in existing literature (4-7). here we report a case of distal portion migration of vp shunt through the processus vaginalis into the scrotum. ∗corresponding author: aming chor-ming lin; emergency department, shin kong wu ho-su memorial hospital, 95 wen chang rd, shih lin district, taipei 111 taiwan. tel: 886-02-28332211 ext 2082; fax: 886-02-28353547; email: amingphd@yahoo.com.tw; m002001@ms.skh.org.tw 2. case presentation: a five-month-old male infant was referred to the emergency department with history of right scrotal swelling, which had slowly grown over several days. there was no history of vomiting, diarrhea, hematuria, irritability or scrotum trauma. the patient was born at 28 weeks gestational age, with birthweight of 1020 gr. as a result of prematurity, he had posthemorrhagic hydrocephalus and a left sided vp shunt was placed 3 months after birth. check-up frontal radiography of the chest and abdomen performed after operation is shown in figure 1. on arrival, vital signs were as follows: temperature 36◦c, pulse rate 120 beats/minute, respiratory rate 30 breaths/min, blood pressure 100/62 mmhg and sao2 99%. in physical examination, he appeared malnourished. the right scrotum was found to be distended. bilateral testicles were palpable on both sides. there were no features of shunt malfunction. a complete blood cell count showed the following: leukocyte count 7900/mm3; segmented neutrophils 65%; hemoglobin level 9.3 mg/dl; hematocrit 25.9%; and platelet 190000/ul. other laboratory studies included: glucose 92 mg/dl; serum urea nitrogen 10 mg/dl; serum creatinine 0.2 mg/dl; sodium 140 meq/l; potassium 3.9 meq/l; c-reactive protein 2.9mg/l; and prothrombin time with an international normalized ratio of 1.2. the patient underwent an abdomen x-ray that is shown in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. hung et al. 2 figure 1: abdominal radiography of patients after ventriculoperitoneal shunt placement. figure 2. abdomen x-ray showed the shunt tube in the abdomen, which was twisted and kinked in its distal portion and coiled in the right scrotum. operation was performed by right groin incision. the peritoneal end of the shunt was repositioned in the peritoneal cavity, and the processus vaginalis was closed. the patient had an uneventful postoperative recovery and was discharged four days later. 3. discussion: vp shunts are catheters that are inserted into the ventricles within the brain and threaded under the skin from the skull to the peritoneum, where excess csf is drained (2). vp shunting for hydrocephalus is one of the most common operations in pediatric neurosurgery. shunt is placed to divert csf from the dilated ventricles to the peritoneal cavity, where it is absorbed. vp shunting is associated with well-known complications including over drainage, obstruction or malfunction, infection, coiling, migration, knotting and viscous perforation (8-11). vp shunt complications are classified as mechanfigure 2: abdominal radiography of patient in emergency department. ical, functional and infective. shunt infection is the most common post-operative complication. another common complication of a vp shunt is shunt obstruction or malfunction. the definitive treatment for both infection and shunt obstruction is surgical shunt revision. a proper clinical assessment leads to timely identification of complications and their prompt treatment. infants with vp shunts should be monitored lifelong by neurosurgeons. migration of the distal catheters of vp shunt is a rare complication. the distal catheter of vp shunt can migrate into various body parts. migration of vp shunt has been reported in several body compartments, including the mediastinum, chest, abdominal wall, gastrointestinal tract, and pelvic cavity (11, 12). common presentations of vp shunt malposition complications include peritonitis, gastrointestinal perforation, ileus, inguinal hernia, peritoneal pseudocysts, loss of catheter into the peritoneal cavity, and abscesses. most of these patients present with abdominal signs. migration occurs when the shunt tube moves from its original position to a location that inhibits proper drainage. migration of the distal portion of the shunt through the processus vaginalis into the scrotum is a very rare complication (13). the migration of a tube into the scrotum also requires a patent processus vaginalis. this event can be subsequent to high intra-abdominal pressure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e48 causing migration of the catheter into scrotum. the length of the distal catheter in peritoneal cavity raises the probability of migration. migration can occur due to improper length. in our case, the plain abdominal x-ray showed the shunt tube, which was twisted and kinked in its distal portion and coiled in the right scrotum. gupta m et al. investigated 30 children with full-length peritoneal shunts to recognize the rate of complications. out of the 30 children, the minimum length of the distal catheter placed in peritoneal cavity was 44 cm and the maximum length was 52 cm. it was shown that use of an extended length peritoneal shunt catheter was not associated with an increase in complications and eliminated the need to lengthen the peritoneal catheter for growth of the patient (14). long-term outcome of vp shunt placement in infants revealed a relatively high rate of complications requiring shunt revision as late as 30 years after initial placement (15). usually the primary image is easily accessible and frequently compared to newly taken images to diagnose migration of the distal catheter of vp shunt. a high index of suspicion is required when making the diagnosis. diagnosis can be established by plain x-ray of the abdomen, which identifies the distal portion of the shunt tube in the scrotum. prompt surgical management for catheter repositioning is recommended in these cases to avoid the risk of further complications. 4. appendix 4.1. acknowledgements we would like to express our special thanks to shin kong wu ho-su memorial hospital staff. 4.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. conflict of interest none declared. 4.4. funding none declared. references 1. stone jj, walker ct, jacobson m, phillips v, silberstein hj. revision rate of pediatric ventriculoperitoneal shunts after 15 years: clinical article. journal of neurosurgery: pediatrics. 2013;11(1):15-9. 2. woo p, wong h, pu j, wong w, wong l, lee m, et al. primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors. hong kong medical journal= xianggang yi xue za zhi. 2016;22(5):410. 3. wu y, green nl, wrensch mr, zhao s, gupta n. ventriculoperitoneal shunt complications in california: 1990 to 2000. neurosurgery. 2007;61(3):557-63. 4. karaosmanoglu d, metin y, akata d, haliloglu m. an unusual cause of hydrocele: malpositioned ventriculoperitoneal shunt in the scrotum. journal of ultrasound in medicine. 2008;27(1):159-60. 5. acharya r, bhutani a, saxena h, madan v. complete migration of ventriculoperitoneal shunt into the ventricle. neurological sciences. 2002;23(2):75-7. 6. hermann ej, zimmermann m, marquardt g. ventriculoperitoneal shunt migration into the pulmonary artery. acta neurochirurgica. 2009;151(6):647-52. 7. borkar sa, satyarthee g, khan rn, sharma b, mahapatra a. spontaneous extrusion of migrated ventriculoperitoneal shunt catheter through chest wall: a case report. turkish neurosurgery. 2008;18(1):95-8. 8. mohammadi a, hedayatiasl a, ghasemi-rad m. scrotal migration of a ventriculoperitoneal shunt: a case report and review of literature. medical ultrasonography. 2012;14(2):158-60. 9. ul-haq a, al-otaibi f, alshanafey s, sabbagh m, al shail e. ventriculoperitoneal shunt peritoneal catheter knot formation. case reports in neurological medicine. 2012;2013:628493-. 10. mohindra s, sharma m. spontaneous knotting of peritoneal catheter: a report of an asymptomatic patient. journal of pediatric neurosciences. 2012;7(2):151-3. 11. chung j, yu j, kim j, nam s, kim m. intraabdominal complications secondary to ventriculoperitoneal shunts: ct findings and review of the literature. ajr american journal of roentgenology. 2009;193(5):1311-7. 12. oktem i, akdemir h, koc k, menku a, tucer b, selcuklu a, et al. migration of abdominal catheter of ventriculoperitoneal shunt into the scrotum. acta neurochirurgica. 1997;140(2):167-70. 13. karaosmanoglu d, metin y, akata d, haliloglu m. an unusual cause of hydrocele: malpositioned ventriculoperitoneal shunt in the scrotum. journal of ultrasound in medicine: official journal of the american institute of ultrasound in medicine. 2008;27(1):159-60. 14. gupta m, digra nc, sharma n, goyal s, agrawal a. length of peritoneal end of shunt catheters in hydrocephalus in children and rate of complications. journal of cranio-maxillary diseases. 2012;1(1):12. 15. bir, s.c., konar, s., t.k. et al. outcome of ventriculoperitoneal shunt and predictors of shunt revision in infants with posthemorrhagic hydrocephalus. childs nerv syst 2016; 32:1405-14. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 18 emergency (2014); 2 (1): 18-21 original research short-term outcome of discharged low-risk chest pain without provoke ischemia study anita sabzghabaei 1, setareh asgarzadeh2*, reza miri3, majid shojaee2, hossein alimohammadi2, kamran heidari1 1.department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran 2.department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of cardiology, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: chest pain is a common problem in patients referring to emergency units. the present study was undertaken to evaluate the short-term outcome of patients presenting with a low risk chest pain and discharging without provoke ischemia study during emergency department admission. methods: in the present prospective cohort study, patients with low-risk chest pain, referring to the emergency department of imam hossein hospital, tehran, during the first half of 2012, were evaluated. all the patients underwent electrocardiogram (ecg) and cardiac enzyme tests, including cardiac isoenzymes creatine kinase mb and troponin i. one week after referring to the emergency department, the patients underwent an exercise test and were followed for a month. data were analyzed with chi-squared test at a significant level of p<0.05. results: a total of 252 patients were included. the mean and standard deviation of patient ages was 56±7.7 years (47.5% male). the results of exercise tests for 47 (26.3%) subjects were positive [32 (28.8%) patients in the 41-60 year age group and 15 (22.7%) over 60 years of age].the angiography examination results of 5 patients (2.8%) were abnormal. there were no significant relationships between the age and gender and the results of exercise test and angiography (p>0.05). during the onemonth follow-up no cases of mortality, cardiac problems, or referring again to the hospital were recorded. conclusion: based on the results of the present study, prevalence of cardiac etiology in patients with low risk chest pain was 2.8% and one-month follow-up did not reveal any complications or serious problems in such cases. key words: chest pain; coronary artery disease; exercise test; risk; emergency cite this article as: sabzghabaei a, asgharzade s, miri r, shojaee m, alimohammadi h, heidari k. short-term outcome of discharged low-risk chest pain without provoke ischemia study. emergency. 2014;2(1):18-21. introduction:1 hest pain is a common complaint of patients referring to emergency units and might be the only symptom of a life-threatening cardiovascular problem (1). it is so important that even in atypical cases, the initial examinations are necessary to rule out a cardiac etiology (2). studies have shown that 2-5% of patients suffering acute myocardial infarction are not properly monitored and are erroneously discharged from emergency units (3). therefore, physicians prefer to take measures to prevent such mistakes. on the other hand, two-thirds of patients presenting with chest pain are ultimately discharged from the hospital without the need for hospitalization or a specific therapeutic intervention (4). however, a sizeable proportion of patients presenting with a chief compliant of chest pain, who have normal electrocardiogram (ecg), are finally diagnosed with acute coronary syndrome after further *corresponding author: setareh asgarzadeh, department of emergency medicine, imam hossein hospital, shahid madani avenue, tehran, iran. telefax: 00982177558081; email address: asgarzade_s_md@yahoo.com received: 7 december 2013; accepted: 8 january 2014 evaluations (5). to prevent such problems, it is necessary to prepare systematic and standard therapeutic protocols based on which it would be possible to discharge patients with greater confidence. initial research studies indicated that morbidity and mortality are rare in low-risk patients; therefore, such patients do not need aggressive treatment modalities and long-term hospitalization, because one-year mortality rate in such patients is approximately 3% and none of them are due cardiac reasons (6, 7). based on the latest recommendation of american heart association in 2010 (8) patients with possible acute coronary syndrome could be discharged from emergency unit if they had normal serial electrocardiography, cardiac enzyme, and negative result of provoke ischemia study (for example the exercise test). since in our country the facility of provoke ischemia study is not available in emergency departments, the low-risk patients, referring to the studied hospital clinic for further evaluation, has been discharged. accordingly, the present study was undertaken to evaluate the short-term outcome of patients presenting with a low risk chest pain and discharging c mailto:asgarzade_s_md@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 19 sabzghabaei et al without provoke ischemia study during emergency department admission. methods: study design and setting the present prospective cohort study was carried out during the first half of 2012 in patients with low-risk chest pain, referring to the emergency department of imam hossein third-level educational hospital in tehran. the protocol of the study was approved by the ethics committee of shahid beheshti university of medical sciences (code: 90-1-134-8723-8303). before the study was instituted, the patients and the people accompanying them received full explanation about the study and those wanted to be volunteer in the study, signed a consent form and were included. participants the subjects in the present study consisted of patients with a chief complaint of chest pain, who had referred to the emergency department and were placed in group iv cardiac risk (low risk) based on classification of the american heart association (9). the included criteria consisted of chest pain with low risk (group iv) and normal ecg and cardiac enzymes. excluded criteria were age >70, persistent angina, history of myocardial infarction, diabetes mellitus, history of heart failure, prior coronary revascularization within five years, hypertension, vascular disease, patients with arrhythmias and heart conduction defects, patients with permanent pacemakers and implantable cardioverterdefibrillators, pulmonary arterial disease, hypertrophic cardiomyopathy, patients with morbid obesity, pregnancy, and lack of interest in participating in the study. data collection serial evaluation of ecgs was carried out and the cardiac enzymes, including troponin i and cardiac isoenzymes creatine kinase mb, were checked. cardiac enzymes were evaluated every six hours up to three times. in addition, ecgs were evaluated whenever chest pain recurred. the age, gender, marital status, occupation, living place, and phone number of patients were questioned and registered. they were asked to refer to the exercise test unit of imam hossein hospital during one week after discharging. when the patients returned to the exercise test unit they were asked about the incidence of cardiac symptoms and signs, recurrence of chest pain or referring to the treatment center again. after the exercise test, the results were collected and patients with positive test underwent angiography. then, the patients were followed for a month. at the time of discharge, the patients or their relatives received instructions in relation to the symptoms and signs of cardiac diseases. endpoints primary endpoints of the study were cardiac etiology of chest pain and mortality during the first week of follow up. also, secondary endpoints were defined as the occurrence of any dysrhythmia, the recurrence of chest pain, cardiac problem, requiring coronary intervention, and repeated emergency department presentation with a complaint of chest pain or other hospitalization as well as mortality during follow-up period. statistical analysis sample size was determined based on the prevalence of cardiovascular complications in patients presenting with low-risk chest pain. since, the lowest prevalence of cardiovascular complications in these patients was 0.2% (19), the minimum samples size was calculated to be 120 subjects by considering α=0.05 and a power of 90% (β=0.1). data were analyzed using spss 21.0. after descriptive evaluation of data, chi-squared and fisher’s exact tests were used to evaluate the outcome of patients. statistical significance was defined as p <0.05. results: a total of 252 patients were included in the present study, with 179 (71.0%) returning to the exercise test unit of imam hossein hospital after a week. the mean and standard deviation of patient ages was 56±7.7 years (47.5% male). the majority of patients were high school graduates (45.0%). patient outcomes of 179 patients referring to the exercise test unit, 47 patients (26.3%) had positive test results [22 (25.9%) male and 25 (26.6%) female]. statistical analysis did not reveal a relationship between age (p=0.4) and gender (p=0.91) of the patients and the results of exercise test. no positive exercise test results were observed in the 20-40-year age group. however, 32 patients (28.8%) in the 41-60-year age group and 15 patients (22.7%) over 60 years of age had positive exercise test results (table 1). the angiography results of 5 patients (2.8%) were abnormal. there was no significant relationship between age (p=0.52), gender (p=0.22), occupational status (p=0.17), and educational level (p=0.13) with the results of angiography. one-month follow-up of patients referring to the exercise test unit showed that there were no complications, such as pain with cardiac origin, infarction, mortality, and dysrhythmia. in addition, 73 patients, not referring to the exercise test unit, were followed. sixty-one of these patients (83.6%) reported that their chest pain had subsided without recurrence. however, 12 patients (16.4%) reported the recurrence of chest pain without hospital re-admission. discussion: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (1): 18-21 20 the results showed that more than a quarter of disposed patients (26.3%) based on the study protocol had positive provoke ischemia study (exercise test) on oneweek follow up and 2.8% of them had positive cardiac angiography findings. none of them exhibited lifethreatening complications during a one-month followup. it can be concluded that, in spite of sizeable number of positive exercise tests in low-risk patients, cardiac etiology has a low prevalence. the results of the present study are consistent with those of other studies. they showed a low prevalence rate of cardiac etiology in patients with low-risk chest pain. for example, brush et al. concluded that only 6% of patients presenting chest pain and normal ecg developed life-threatening complications (10). also, the results of a study by kelly et al. indicated a low prevalence rate of cardiac outcomes in such patients (11). amsterdam et al. did not report any case of mortality during a one-month follow-up in patients whose exercise test results were negative; they reported only one case of myocardial infarction (0.01%). in addition, in patients with positive exercise test results four cases (0.04) of myocardial infarction and 12 cases (0.12) of myocardial revascularization were observed (2). holly et al. reported that patients with a moderate risk, compared to low-risk patients, exhibited higher rates of myocardial infarction, stenting, coronary artery bypass graft (cabg), and hospitalization (12). the results of long-term studies were not significantly different from those of the present study. for example, a six-month follow-up in a study by meyer et al. showed that the etiology of 98% of patients presenting with chest pain was non-cardiac (13), consistent with the results of other studies (14, 15). a study by hollander et al. showed that the prevalence of a cardiac etiology in low-risk patients was 15%; however, despite the high prevalence of cardiac etiology, no deaths or serious complications were reported. the researchers concluded that even if the cardiac etiology prevalence in low-risk patients is high in relation to the incidence of cardiac complication, the incidence of lifethreatening complications would be very rare (16). based on what was discussed, it is hypothesized that the incidence of serious complications in low-risk patients with chest pain is rare and it might be possible to discharge such patients without therapeutic intervention. however, the risk of myocardial infarction should not be overlooked in such cases; because there is a high risk for silent myocardial infarction in young patients with atypical symptoms and signs without a history of angina or coronary heart disease (17-21). conclusion: based on the results of the present study, the prevalence of cardiac etiology in low-risk patients, presenting with chest pain, was 2.8% and a one-month follow-up did not reveal any serious problems and complications in such cases. acknowledgments: we would like to thank the emergency department staffs of imam hossein hospital for helping us in conducting this study. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of international committee of medical journal editors. references: 1. nasrallah n, steiner h, hasin y. the challenge of chest pain in the emergency room: now and the future. eur heart j. 2011;32:656. 2. amsterdam ea, kirk jd, bluemke da, et al. testing of lowrisk patients presenting to the emergency department with chest pain a scientific statement from the american heart association. circulation. 2010;122(17):1756-76. 3. savitz si, caplan lr, edlow ja. pitfalls in the diagnosis of cerebellar infarction. acad emerg med. 2007;14(1):63-8. 4. goodacre s, cross e, arnold j, angelini k, capewell s, nicholl j. the health care burden of acute chest pain. heart. 2005;91(2):229-30. 5. moe kt, wong p. current trends in diagnostic biomarkers of acute coronary syndrome. ann acad med singapore. 2010;39(3):210-5. 6. potts s, bass c. psychosocial outcome and use of medical resources in patients with chest pain and normal or nearnormal coronary arteries: a long-term follow-up study. q j med. 1993;86(9):583-93. 7. wielgosz at, fletcher rh, mccants cb, mckinis ra, haney tl, williams rb. unimproved chest pain in patients with table 1: patients’ demographic data stratified by exercise test  variable negative positive p number (%) number (%) age 0.47 20-40 2 (100.0) 0 (0.0) 41-60 79 (71.2) 32 (28.8) >60 51 (77.3) 15 (22.7) gender male 63 (74.1) 22 (25.9) 0.91 female 69 (73.4) 25 (26.6) occupation housewife 38 (71.7) 15 (28.3) 0.76 employee 37 (75.5) 12 (24.5) selfemployed 42 (77.8) 12 (22.2) education level high school 26 (66.7) 13 (33.3) 0.34 high school graduate 54 (71.1) 22 (28.9) academic 43 (79.6) 11 (20.4) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 21 sabzghabaei et al minimal or no coronary disease: a behavioral phenomenon. am heart j. 1984;108(1):67-72. 8. lloyd-jones d, adams rj, brown tm, et al. heart disease and stroke statistics—2010 update a report from the american heart association. circulation. 2010;121(7):e46e215. 9. tintinalli je, stapczynski js, ma oj, cline d, cydulka r, meckler g. tintinalli's emergency medicine: a comprehensive study guide: mcgraw-hill medical; 2011. p. 392. 10. brush jr je, brand da, acampora d, chalmer b, wackers fj. use of the initial electrocardiogram to predict in-hospital complications of acute myocardial infarction. n engl j med. 1985; 313(11):692-4. 11. kelly a-m. what is the incidence of major adverse cardiac events in emergency department chest pain patients with a normal ecg, thrombolysis in myocardial infarction score of zero and initial troponin≤ 99th centile: an observational study? emerg med j. 2013;30(1):15-8. 12. holly j, hamilton d, bledsoe j, et al. prospective evaluation of the treatment of intermediate-risk chest pain patients in an emergency department observation unit. crit pathw cardiol. 2012;11(1):10-3. 13. meyer mc, mooney rp, sekera ak. a critical pathway for patients with acute chest pain and low risk for short-term adverse cardiac events: role of outpatient stress testing. ann emerg med. 2006; 47(5):427-35. 14. lai c, noeller tp, schmidt k, king p, emerman cl. shortterm risk after initial observation for chest pain. j emerg med. 2003;25(4):357-62. 15. may jm, shuman wp, strote jn, et al. low-risk patients with chest pain in the emergency department: negative 64mdct coronary angiography may reduce length of stay and hospital charges. am j roentgenol. 2009;193(1):150-4. 16. hollander je, litt hi, chase m, brown am, kim w, baxt wg. computed tomography coronary angiography for rapid disposition of low‐risk emergency department patients with chest pain syndromes. acad emerg med. 2007;14(2):112-6. 17. thygesen k, alpert js, jaffe as, et al. third universal definition of myocardial infarction. j am coll cardiol. 2012;60(16):1581-98. 18. toma m, fu y, ezekowitz ja, et al. does silent myocardial infarction add prognostic value in st-elevation myocardial infarction patients without a history of prior myocardial infarction? insights from the assessment of pexelizumab in acute myocardial infarction (apex-ami) trial. am heart j. 2010;160(4):671-7. 19. davis tm, coleman rl, holman rr. prognostic significance of silent myocardial infarction in newly diagnosed type 2 diabetes mellitus clinical perspective united kingdom prospective diabetes study (ukpds) 79. circulation. 2013;127(9):980-7. 20. arenja n, mueller c, ehl nf, et al. prevalence, extent, and independent predictors of silent myocardial infarction. am j med. 2013;126(6):515-22. 21. valensi p, lorgis l, cottin y. prevalence, incidence, predictive factors and prognosis of silent myocardial infarction: a review of the literature. arch cardiovasc dis. 2011;104(3):178-88. archives of academic emergency medicine. 2023; 11(1): e8 rev i ew art i c l e value of n-terminal pro-brain natriuretic peptide for embolic events risk prediction in patients with atrial fibrillation; a systematic review and meta-analysis koohyar ahmadzadeh1, amirali hajebi2, hamzah adel ramawad3, yaser azizi1,4∗, mahmoud yousefifard1,5 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. non-communicable diseases research center, endocrinology and metabolism population sciences institute, tehran university of medical sciences, tehran, iran. 3. department of emergency medicine, nyc health & hospitals coney island, new york. 4. department of physiology, school of medicine, iran university of medical sciences, tehran, iran. 5. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: a comprehensive conclusion has yet to be made about the predictive value of serum n-terminal pro-brain natriuretic peptide (nt-probnp) for stroke/systemic embolic events (see) in patients with atrial fibrillation (af). this study aims to review the evidence for evaluating the value of nt-probnp in predicting the risk of stroke/see in patients with af through a systematic review and meta-analysis. methods: two independent reviewers screened all relevant studies that were retrieved from the database of medline, embase, scopus, and web of science until december 7th, 2021. the predictive value of nt-probnp in the prediction of stroke/see was recorded as hazard ratio (hr) and 95% confidence interval (95% ci). results: nine articles (38,093 patients, 3.10% stroke/see) were included in our analysis. there was no publication bias in these studies (p=0.320). our analysis showed that nt-probnp can be a good predictor of stroke/see risk in af patients, even at different cut-off values (hr=1.76; 95% ci: 1.51, 2.02; p < 0.001). subgroup analysis showed that diabetes could have a possible effect on the predictive value of nt-probnp (meta-regression coefficient = 0.042; p = 0.037). conclusion: measurement of nt-probnp during the first admission could be used to assess the shortor long-term risk of stroke/see in patients with af. further studies are needed to evaluate the possible applicability of serum nt-probnp measurement in the settings in which stroke is the sole outcome of the investigation. keywords: pro-brain natriuretic peptide; stroke; embolism, paradoxical; atrial fibrillation; meta-analysis cite this article as: ahmadzadeh k, hajebi a, ramawad ha, azizi y, yousefifard m. value of n-terminal pro-brain natriuretic peptide for embolic events risk prediction in patients with atrial fibrillation; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e8. https://doi.org/10.22037/aaem.v11i1.1808. 1. introduction stroke and thromboembolic events are considered as one of the leading causes of death and disability worldwide (1, 2). in the past, stroke was believed to be a disease that mostly af∗corresponding author: yaser azizi; physiology research center, iran university of medical sciences, tehran, iran. tel: +982188622709; email: azizi.y@iums.ac.ir, orcid: https://orcid.org/???. † corresponding author: mahmoud yousefifard; physiology research center, school of medicine, iran university of medical sciences, shahid hemmat highway, tehran 14496-14535, iran. tel: +98 (21) 86704771; email: yousefifard.m@iums.ac.ir / yousefifard20@gmail.com, orcid: https://orcid.org/???. fected the elderly population. however, recent studies have shown that the incidence of stroke in the younger population is increasing (3-5). regardless of the age group, there is a high prevalence of cardiovascular accidents worldwide, which results in lifelong disabilities and death in severe cases (6, 7). there are many risk factors associated with a higher occurrence of stroke, such as hypertension, diabetes, old age, smoking, and sedentary lifestyle (8, 9). atrial fibrillation (af), an irregular rapid beating of the atriums (10), increases the risk of strokes and other thromboembolic events. it is well established that patients with atrial fibrillation are at higher risk for strokes and systemic thromboembolic events compared to patients without af (11, 12). the identification of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index k. ahmadzadeh et al. 2 high-risk patients for stroke is commonly made by using a clinical score such as the chads2, a scoring system designed to predict the risk of stroke in patients with atrial fibrillation based on their risk factors (heart failure, hypertension, age > 75, diabetes, prior stroke/ transient ischemic attack (tia), vascular disease, ages 65-75, and sex category) (13, 14). in addition to the availability of clinical scoring tools, there is still a need for additional simple, accurate, and reliable markers for the identification of patients with a higher risk of stroke in the clinical setting. in recent years, serum biomarkers such as natriuretic peptides have been mentioned as a suitable marker for predicting stroke and systemic embolic events (see) in patients with af (15, 16). studies have shown that nt-probnp levels are often elevated in patients with af, which can be used as a tool for predicting the risks of adverse outcomes such as strokes (11). there are various isoforms and metabolites of natriuretic peptides, including natriuretic brain peptide, atrial natriuretic peptide, and n-terminal pro-brain natriuretic peptide (nt-probnp). nt-probnp is an inactive prohormone secreted primarily by cardiac cells (17). an increase in this prohormone has been reported in patients with af, and elevated levels of this protein are associated with an increased risk of stroke and mortality (16, 18, 19). despite various existing studies, a conclusion has not yet been reached about the possible use of serum nt-probnp levels for predicting the occurrence of stroke/see in patients with af. this study aims to review the evidence for evaluating the value of n-terminal pro b-type natriuretic peptide in predicting stroke/see in patients with atrial fibrillation through a systematic review and meta-analysis study. 2. methods 2.1. study design and settings the present study is a systematic review and meta-analysis designed to evaluate the predictive value of serum ntprobnp levels for the occurrence of stroke/see in patient with af. in this study, pico was defined as: patients (p): patients with atrial fibrillation, index test (i): serum nt-probnp levels, comparison (c): af patients who did not develop stroke/see outcome (o): occurrence of stroke/see. 2.2. search strategy the keywords for our search were extracted with the help of experts in the field and by reviewing the titles of relevant papers. synonyms and equivalent words were identified using mesh and emtree databases. the search strategy was modified based on the standard boolean operators and standard tags of the medline, embase, scopus, and web of science databases. extensive searches were performed on each of the mentioned databases for papers published until december 7th, 2021 (online resources). additionally, google and google scholar search engines were used to search for gray literature and non-indexed material. finally, the citations and bibliography of the eligible articles were reviewed to find any papers that might have been missed. 2.3. selection criteria all observational or trial studies investigating the relationship between serum nt-probnp levels and the occurrence of stroke/see in patients with af were included. exclusion criteria were: not having a non-stroke/non-see group, not having a stroke/see as an outcome, not reporting data for nt-probnp, not having af as the etiology of stroke/see, not reporting a hazard ratio (hr), not reporting original data, not having any valuable data, study protocol publications, editorials, letter to editors, duplicates, and reviews. 2.4. data collection two independent reviewers performed title and abstract screening of the potentially related articles, after which the retrieved full texts were studied, and the applicable studies were included. finally, the information provided by the included studies was extracted into a checklist. any dispute in this process was resolved using the opinion of a third reviewer. the extracted data comprised study characteristics (name of the first author, year of publication, and country), study type, setting of included patients, sample size, age, gender distributions, the prevalence of underlying diseases, follow-up duration, and number of stroke/see patients. the predictive value of nt-probnp in prediction of stroke/see was recorded as hazard ratio (hr) and 95% confidence interval (95% ci). 2.5. risk of bias and certainty of evidence assessment the included articles were designed as cohort studies and randomized clinical trials (rcts). all the included articles were considered prognostic studies and thus their quality was evaluated using the quality in prognosis studies (quips) guidelines (20). grading of recommendations, assessment, development and evaluations (grade) framework was used to evaluate the level of evidence of the included articles (21). all the evaluations were done independently by two researchers and in cases of disagreement, the third reviewer was consulted. 2.6. statistical analysis all analyses were performed using stata 17.0 statistical program. the relationship between nt-probnp serum values and occurrence of stroke/see was evaluated by reporting a pooled hr using the “meta” command. heterogeneity between the included studies was assessed by using i2 statisthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 3 archives of academic emergency medicine. 2023; 11(1): e8 tics, and while there was no heterogeneity, meta-regression was performed to analyze the data further. the effect of different cut-off values, follow-up duration, prevalence of diabetes, hypertension, heart failure and other underlying diseases of the population on the predictive value of nt-probnp for stroke/see in patients with af was investigated. a sensitivity analysis was also performed according to the quality of the included studies. lastly, publication bias was examined using egger’s test. 3. results 3.1. study characteristics the systematic search in four online databases of pubmed, embase, scopus and web of science resulted in 3,902 articles, from which 2,356 were non-duplicates. title and abstract screening were performed on the remaining articles, 144 of which were potentially eligible. a total of 8 articles were included in this meta-analysis after the full-text screening. a manual search resulted in an additional article. therefore, a total of 9 papers were included in our analysis (15, 22-29) (figure 1). four articles had a randomized clinical trial design, and five were designed as prospective cohort studies. the studies compromised data on 38,093 patients, 21,972 of which were male. during the average follow-up time of roughly three years, 3.10% of patients experienced a stroke/see. the general characteristics of the included papers are summarized in table 1. 3.2. risk of bias and publication bias the quality of the studies was assessed using the quips assessment tool for the prognostic studies. two studies were found to have moderate risk of bias in study participation domain due to small sample size, two studies were found to have moderate risk in study attrition domain due to no reports of samples lost to follow-up and in domain of outcome measurement two studies were found to have moderate risk and the risk of one study was classified as unclear, due to unspecific description of outcome assessment method. risk of bias was low in all the remaining domains of the guideline (table 2). as for the publication bias, egger’s test was used, and the results showed that there was no publication bias in the studies regarding the prognostic use of nt-probnp in prediction of stroke/see in af patients (p= 0.320) (figure 2). 3.3. meta-analysis relationship between nt-probnp serum values and occurrence of stroke/see in patients with af our analysis showed that serum levels of nt-probnp can be a good predictor of stroke/see occurrence in patients with af, even at different cut-off values (hr= 1.76; 95% ci: 1.51, 2.02; p < 0.001). a detailed presentation of the effect size for each study is shown in figure 3. also, no heterogeneity was reported between the included studies using the i2 statistic (i2 = 15.2%, p = 0.50) meta-regression although there was no heterogeneity between the included studies, meta-regression was done to investigate the possible effects of confounders on the predictive value of ntprobnp (table 3). the analysis showed that from all the investigated factors, only diabetes could have a possible effect on the predictive value of nt-probnp (meta-regression coefficient=0.042; p = 0.037). other factors such as cut-off values (p = 0.970), follow-up duration (p = 0.392), hypertension (p = 0.052), heart failure (p = 0.140), prior myocardial infarction (mi) (p = 0.245), history of stroke or tia or systemic embolism (p = 0.329), previous peripheral artery disease (p = 0.591), previous coronary artery disease (p = 0.638) and sample size (p = 0.761) did not have any noticeable effect on the predictive value of nt-probnp for occurrence of stroke/see in af patients (figure 4). certainty of evidence level of evidence were evaluated using the grade framework. since the nature of assessments in the included papers were observations of prognostic value of nt-probnp, despite the rct design of some of them, the initial level of evidence was considered to be low. evidence for stroke/see was rated to be moderate, one point increase due to the dose-response gradient effect was observed. however, evidence for stroke alone was rated as low, one point increases due to the doseresponse gradient effect, and one point decrease due to the small sample size of the studies were observed. (table 4). summary of findings is demonstrated in table 5. sensitivity analysis to assess the effects of the overall quality of the included studies on the reported effect size, we divided the studies into 2 groups of “low risk” and “unclear”. the analysis showed that the reported effect size for “low risk” articles (hr = 1.774; 95% ci: 1.50, 2.05; i2 = 19.41) did not have a significant difference with the effect size reported for “unclear” articles (hr = 1.731: 95% ci: 1.02, 2.44; i2 = 20.10) (meta-regression coefficient = -0.06; 95% ci: -0.77, 0.65; p = 0.864). 4. discussion the current study aimed to review and summarize existing literature regarding the possible predictive applicability of serum nt-probnp levels for predicting the occurrence of stroke/see in patients with af. our analysis showed that abnormally high serum levels of nt-probnp, at any of the cutoff points and at any follow-up duration used by the included studies, had a significant correlation with stroke/see occurthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index k. ahmadzadeh et al. 4 rence in patients with af. although no heterogeneity was observed between the studies, we conducted a meta-regression to evaluate our results further. the value of nt-probnp in predicting stroke/see in patients with af was shown to be affected by diabetes. therefore, diabetic patients with af and high levels of ntprobnp are at higher risk of stroke/see compared to af patients without diabetes. it has been reported that higher levels of nt-probnp is associated with higher rates of vascular complications among individuals who developed type 2 diabetes (30). this is a possible explanation for the confounding effect of diabetes on the predictive value of serum ntprobnp. various cut-off points used by the studies did not affect the capability of serum nt-probnp levels for prediction of stroke/see in patients with af. nt-probnp levels could be measured even with the lowest cut-off value and still be helpful in stroke/see prediction. the lowest cut-off used in the included studies was 169 pg/ml. appropriately, this cut-off can be used to evaluate the risk of stroke/see in patients with af. the follow-up duration in the included studies varied between 1 and 5 years. our results show that serum levels of ntprobnp is a good predictor of stroke/see in patients with af at any follow-up duration. therefore, a one-time measurement of serum nt-probnp levels during the first admission to the hospital can be a good predictor of stroke/see even at longer follow-ups. considering that neither cut-off values nor follow-up duration differences influenced the predicting capabilities of serum nt-probnp, it can be implied that measurement of nt-probnp can be a helpful risk assessment tool in clinical settings. to the best of our knowledge one meta-analysis has studied the association between natriuretic peptides (bnp and ntprobnp) and atrial fibrillation (31). in their study, hong et. al, have reported a hazard ratio of 2.53 (95% ci 2.00, 3.19) for the pooled value of bnp and nt-probnp in prediction of stroke/see in af patients; however, the predictive value of nt-probnp alone has only been evaluated with four included studies with a reported risk ratio of 2.43 (95% ci 1.90, 3.11). our study further solidifies the predictive value of ntprobnp in evaluation of stroke/see in af patients with a larger number of included articles and a larger sample size. additionally, we have also considered the medical characteristics of the included populations and have provided a possible cut-off for the use of nt-probnp in the evaluation of the risk of stroke/see in patients with af. 5. limitation this systematic review and meta-analysis has its limitations. the primary goal of the study was to investigate the possible predictive value of serum nt-probnp for stroke as the sole outcome; but only three studies met this criterion, while other studies had pooled the data of stroke with see. as a result, this study should be used cautiously in the setting of stroke alone. further studies could shed more light on the predictive applicability of nt-probnp for stroke as the sole outcome. another limitation of this study was the incomplete report of some of the demographic information and the fact that the full text of one of the included articles could not be found, even after multiple email inquiries to their corresponding authors. as for the strength of this study, it is worth noting that no heterogeneity and no publication bias were observed in the included studies. different sample sizes of the included studies did not affect the predictive value reported by the articles; this shows that none of the included articles had insufficient sample size. 6. conclusion the results of our study show that there is a significant association between serum levels of nt-probnp and the risk of stroke/see in patients with af. measurement of serum ntprobnp can be used as a clinical tool to assess the short term or long-term risk of stroke/see in patients with af during first the admission to the hospital. despite our findings, further studies are needed to evaluate the possible applicability of serum nt-probnp measurement in settings with stroke as the sole outcome of the investigation. 7. declarations 7.1. acknowledgments not applicable. 7.2. conflict of interest the authors declare that there is no conflict of interest. 7.3. fund this study has been funded and supported by the iran university of medical sciences (iums); [grant no: 1400-1-3220043.] 7.4. authors’ contribution study design and conception: yousefifard m, azizi y; data gathering: all authors; analysis: yousefifard m; drafting and revising: all authors. 7.5. data availability data can be shared at the request of any qualified investigator for purposes of replicating procedures and results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 5 archives of academic emergency medicine. 2023; 11(1): e8 references 1. johnson co, nguyen m, roth ga, nichols e, alam t, abate d, et al. global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the global burden of disease study 2016. lancet neurol. 2019;18(5):439-58. 2. wendelboe am, raskob ge. global burden of thrombosis. circ res. 2016;118(9):1340-7. 3. smajlović d. strokes in young adults: epidemiology and prevention. vasc health risk manag. 2015;11:157-64. 4. george mg. risk factors for ischemic stroke in younger adults: a focused update. stroke. 2020;51(3):729-35. 5. renna r, pilato f, profice p, della marca g, broccolini a, morosetti r, et al. risk factor and etiology analysis of ischemic stroke in young adult patients. j 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2021;10(15):e020157. 29. tomasdottir m, hijazi z, lindback j, benz a, connolly sj, eikelboom jw, et al. abstract 10162: nt-probnp is associated with stroke, heart failure hospitalizations, and death in patients with atrial fibrillation without oral anticoagulation regardless of heart rhythm. circulation. 2021;144(suppl_1):a10162. 30. birukov a, eichelmann f, kuxhaus o, polemiti e, fritsche a, wirth j, et al. opposing associations of nt-probnp with risks of diabetes and diabetes-related complications. diabetes care. 2020;43(12):2930-7. 31. du h, yang l, zhang h, zhang x, shao h. association of natriuretic peptide and adverse outcomes in patients with atrial fibrillation: a meta-analysis. clin exp pharmacol physiol. 2020;48(2):161-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 7 archives of academic emergency medicine. 2023; 11(1): e8 table 1: characteristics of included studies study, year, registry, country design participants no. cases age* male medical history followup (year) outcome n event hf htn dm stroke/ tia/se mi cad pad berg, 2018, engage af-timi 48, multinational rct af and chads2 score ≥2. 8705 72 (64-78) 5330 59.4 95.5 37 28 nr 34.8 4.4 2.8 stroke/ see 139 ha, 2011, na, korea pcs af patients 200 68.9 ± 11.7 38 nr 49 18.5 15 nr nr nr 1.26 stroke 14 hamatani, 2021, fushimi, japan pcs af patients w/o hf 1159 72.1 ± 10.2 718 nr 69.7 20.2 14.3 nr 13.2 8.2 5 stroke/ see 113 hijazi, 2012, rely, multinational rct af patients + at least one of the following risk factors: previous stroke or tia, chf or reduced lvef <40%, age > 75, age > 65 with dm or htn or cad 6189 72 (67-77) 3944 30 78.4 21.4 19.6 17.4 24.9 nr 2.2 stroke/ see 183 hijazi, 2013, aristotle, multinational rct af and at least 1 chads2 risk factor 14892 69 (62-75) 9590 35.9 87.5 30.9 18.7 12.8 nr 4.9 1.9 stroke/ see 393 kuronuma, 2020, sakura, japan pcs non-valvular af, >20 year, receiving oral anticoagulant 2417 72 (66-79) 1777 25.9 72.3 23.5 11.4 nr nr nr 3.25 stroke/ see 107 roldan, 2014, na, spain pcs permanent or paroxysmal af patients, taking oac with stable inr for > 6 months 1172 76 (71-81) 575 30 82 26 19 nr 19 nr 2.75 stroke/ see 51 singleton, 2019, regards, usa pcs af patients 175 66 ± 9 nr nr nr nr nr nr nr nr 5.2 stroke 81 tomasdottir, 2021, averoes & active a, multinational rct af patients, receiving aspirin with no oral anticoagulation 3184 nr nr nr nr nr nr nr nr nr 2.5 stroke nr * age was reported as mean ± sd or median (interquartile range). data of medical history were reported as a percentage of the whole population. rct: randomized clinical trial, pcs: prospective cohort study, hf: heart failure, htn: hypertension, dm: diabetes mellitus, tia: transient ischemic attack, see: systemic embolic event, mi: myocardial infarction, cad: coronary artery disease, pad: peripheral artery disease; nr: not reported; af: atrial fibrillation; chads: congestive heart failure, hypertension, age, diabetes, prior stroke; chf: congestive heart failure; lvef: left ventricular ejection fraction; oac: oral anticoagulant; inr: international normalized ratio. table 2: risk of bias assessment study study participation study attrition prognostic factor measurement outcome measurement study confounding statistical analysis/ reporting berg, 2018 low low low low low low ha, 2011 moderate low low moderate low low hamatani, 2021 low moderate low moderate low low hijazi, 2012 low low low low low low hijazi, 2013 low low low low low low kuronama, 2020 low moderate low unclear low low roldan, 2014 low low low low low low singleton, 2019 moderate low low low low low tomasdottir, 2021 low low low low low low this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index k. ahmadzadeh et al. 8 figure 1: prisma flow diagram of the present study. see: systemic embolic event; af: atrial fibrillation. figure 2: assessment of publication bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 9 archives of academic emergency medicine. 2023; 11(1): e8 figure 3: effect size of the predictive effect of nt-probnp in different cut-off values for the occurrence of stroke/see in af patients. table 3: meta-regression analysis for the effect of confounding factors on the predictive value of nt-probnp for the occurrence of stroke/systemic embolic events (see) in patients with atrial fibrillation variable meta-regression coef. 95% ci p value cut-off point 0.00001 -0.00055, 0.00057 0.970 follow-up duration 0.11156 -0.14374, 0.36687 0.392 diabetes 0.04203 0.00253, 0.08153 0.037 hypertension 0.02357 -0.00023, 0.04738 0.052 heart failure 0.01932 -0.00635, 0.04500 0.140 prior mi -0.08606 -0.23119, 0.05907 0.245 stroke/tia/see 0.02979 -0.03008, 0.08967 0.329 peripheral artery disease -0.07108 -0.33050, 0.18833 0.591 coronary artery disease 0.01336 -0.04233, 0.06906 0.638 sample size 0.00001 -0.00004, 0.00005 0.761 ci: confidence interval; coef.: coefficient; tia: transient ischemic attack; mi: myocardial infarction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index k. ahmadzadeh et al. 10 figure 4: meta-regression for assessment of the effect of cut-off values (a) and percentage of diabetic patients (b) in included studies on the occurrence of stroke/see following atrial fibrillation. table 4: certainty of evidence outcome number of studies (analysis) n n event quality of evidence stroke/see 6 (14) 34534 986 moderate ⊕⊕⊕⊕⊕ + dose-response gradient stroke 3 (5) 375 (+3184) 95 (+nr) low ⊕⊕⊕⊕⊕ª +dose-response gradient small sample size see: systemic embolic events; nr: not reported; n: sample size. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e1 or i g i n a l re s e a rc h the correlation between serum level of vitamin d and outcome of sepsis patients; a cross-sectional study majid shojaei1, anita sabzeghabaei2, helia valaei barhagh1∗, soheil soltani1 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: september 2018; accepted: september 2018; published online: 10 january 2019 abstract: introduction: the effect of vitamin d deficiency in manifestation of sepsis and its role as an important mediator in the immune system has received attention. the present study was done with the aim of evaluating the correlation between serum levels of vitamin d and outcome of sepsis patients. methods: the present cross-sectional study was performed on patients over 18 years of age suspected to sepsis presenting to an emergency department during 1 year using non-probability convenience sampling. for all eligible patients, blood sample was drawn for measurement of serum level of vitamin d3 and the correlation of this vitamin with outcomes such as mortality, renal failure, liver failure and etc. was assessed. results: 168 patients with the mean age of 70.8 ± 13.3 (43.0 – 93.0) years were studied (56.0% male). mean serum level of vitamin d3 in the studied patients was 19.03 ± 13.08 (4.0 – 85.0) ng/ml. by considering 20 – 50 ng/ml as the normal range of vitamin d, 61.6% of the patients had vitamin d deficiency. only age (r=-0.261, p=0.037) and mortality (r=-0.426, p=0.025) showed a significant correlation with mean vitamin d. sepsis patients with older age and those who died had a lower level of vitamin d. area under the roc curve of serum vitamin d level regarding 1-month mortality of the sepsis patients was 0.701 (95%ci: 0.439 – 0.964). conclusion: based on the results of the present study, the prevalence of vitamin d deficiency in sepsis patients presenting to the ed was estimated as 61.6%. a significant and indirect correlation was found between the serum level of vitamin d3 and mortality as well as older age. it seems that consumption of vitamin d supplements might be helpful in decreasing the prevalence of infection, sepsis, and mortality caused by it, especially in older age. keywords: systemic inflammatory response syndrome; sepsis; patient outcome assessment; 24, 25-dihydroxyvitamin d3; mortality cite this article as: shojaei m, sabzeghabaei a, valaei barhagh h, soltani s. the correlation between serum level of vitamin d and outcome of sepsis patients; a cross-sectional study. arch acad emerg med. 2019; 7(1): e1. 1. introduction sepsis is a clinical syndrome caused by immune response to various infections. despite the existence of proper antimicrobial and palliative care, due to the high prevalence of multiple organ failure, being affected with sepsis is associated with a high rate of mortality. more than 31 million sepsis cases, 19 million severe sepsis cases, and 5.3 million deaths a year is a rough estimation of the burden of this disease in high-income countries (1-3). recent studies have shown the correlation between vitamin d deficiency and severe infections and sepsis. in addition, it has been confirmed that vita∗corresponding author: helia valaei barhagh; emergency department, imam hossein hospital, madani avenue, imam hossein square, tehran, iran. tel: 00989111325336 e-mail: valaeebarhagh@gmail.com min d is an important mediator in the immune system and its inhibitory role in sepsis pathogenesis has been evaluated (4-6). vitamin d can regulate acquired and innate immune responses (7). this vitamin prevents overexpression of inflammatory cytokines and is an important mediator in aggregation of leukocytes, formation of local inflammation, and anti-bacterial responses in innate immunity. vitamin d deficiency has been linked to an increase in the risk of initiation and development of viral and bacterial infections (8-10). low serum level of vitamin d on admission of patients to the intensive care unit has correlated with an increase in mortality risk and blood infections (11). additionally, a higher risk of developing sepsis has been shown in patients who have had vitamin d deficiency before hospital admission (7, 10). however, studies in this regard are still ongoing to reach a final decision and the correlation between vitamin d and decrease in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shojaei et al. 2 mortality has not been confirmed in all studies (12-14). iran is among the countries that have a considerable prevalence of vitamin d deficiency in all age groups. iran’s ministry of health has strongly advised using vitamin d supplements for all age groups (15, 16). on the other hand, we are faced with a day by day increase in the number of sepsis patients in emergency departments (ed) and intensive care units. therefore, the present study was designed and performed with the aim of evaluating the correlation between serum levels of vitamin d and outcome of sepsis patients presenting to ed. 2. methods 2.1. study design and setting the present cross-sectional study was performed on patients suspected to sepsis presenting to the ed of imam hossein hospital, tehran, iran, from 2015 to 2016. for all the eligible patients, blood sample was drawn for measuring serum level of vitamin d and finally the correlation between the level of this vitamin and the studied outcomes was evaluated. the study was performed by adhering to the principles of helsinki declaration and approval of the ethics committee of shahid beheshti university of medical sciences. inclusion of patients was done after obtaining informed consent from the patient or their relative. keeping patient data confidential and publishing findings anonymously were among other measures for ethical conduct in this study. 2.2. participants the studied sample included patients over 18 years of age suspected with sepsis presenting to the emergency department in various working shifts, who were selected via nonprobability convenience sampling. sepsis diagnosis was confirmed after clinical examinations, meeting the required criteria and performance of laboratory tests. patients with a history of neuroendocrine diseases, history of mental disorders, shock due to reasons other than sepsis, consumption of corticosteroid drugs, recent and constant use of vitamin d or other supplements including it, pregnant women, those who did not give their consent for participation in the study, and those whose sepsis diagnosis was not confirmed in the end based on the mentioned criteria were eliminated from the study. sepsis was defined as the presence of at least 2 of the symptoms of systemic inflammatory response syndrome (sirs) with the origin of a suspected or confirmed infectious source (17). 2.3. sampling venous blood was drawn from the median cubital vein of the patients for measuring the serum level of vitamin d. blood samples were kept in room temperature for 15-30 minutes and centrifuged (1500 rpm) for 10-15 minutes. consequently, serums were separated and kept in -20◦c until the time of evaluation. after completion of samples, the concentration of serum 25-hydroxy vitamin d3 was measured. measurement of serum concentration of 25-hydroxy vitamin d3 was done with radioimmunoassay method using diasource kit made in belgium and based on the guidelines of the kit. 2.4. data gathering data gathering was done by a trained senior emergency medicine resident using a pre-designed checklist including demographic data (age, sex), laboratory findings, vital signs, level of consciousness, origin of the infection, sepsis severity based on mortality in emergency department sepsis (meds) score, and finally, the outcome of patients (death, renal failure, liver failure, need for mechanical ventilation and etc.). 30-day outcome of the patients (mortality) was gathered by follow-up via phone calls. based on meds score, the patients were divided into 5 groups based on the probability of death including: 1very low probability, 2low probability, 3moderate probability, 4high probability, and 5very high probability. 2.5. statistical analysis sample size required for the present study was determined to be 195 cases, based on the study by rech et al. (6), and considering 54% prevalence of vitamin d deficiency in sepsis patients, 95% confidence interval (ci) and maximum acceptable error in estimation of prevalence as 7%. to describe data, frequency and percentage or mean ± standard deviation were reported. to assess the correlation between various factors and vitamin d deficiency, chi-square, fisher’s exact and anova tests were applied. all analyses were performed using spss 21.0 statistical software. calculation of area under the receiver operating characteristic (roc) curve was applied for determining the cut-off point of serum level of vitamin d in correlation with mortality. in this study, p<0.05 was considered as the level of significance. 3. results 168 patients with the mean age of 70.8 ± 13.3 (43.0 – 93.0) years were studied (56.0% male). tables 1 and 2 depict the baseline characteristics and laboratory findings of the studied patients. mean serum level of vitamin d3 in the studied patients was 19.03 ± 13.08 (4.0 – 85.0) ng/ml. by considering 20 – 50 ng/ml as the normal range of vitamin d, 61.6% of the patients had vitamin d deficiency. crp (p=0.176) and platelet (p=0.951) levels, as 2 important inflammatory indices, were not significantly different between the patients with vitamin d deficiency and others. table 3 shows the correlation between mean serum level of vitamin d and different variables. only age (r=-0.261, p=0.037) and mortality (r=this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e1 table 1: baseline characteristics of studied patients variable value sex male 94.0 (56.0) female 74.0 (44.0) age (year) 40 – 60 39 (23.0) ≥ 60 129 (77.0) vital signs systolic blood pressure (mmhg) 89.41 ± 18.63 pulse rate (/minute) 103.6 ± 9.5 temperature (c) 38.4 ± 0.7 saturation o2 (%) 85.1 ± 9.4 gcs 3 7 16 (9.6) 8 14 87 (50.7) 15 67 (39.7) source of infection pneumonia 46 (31.1) urinary tract infection (ui) 44 (29.7) pneumonia + ui 32 (21.6) bed sore 14 (9.5) multi source 10 (6.9) gastrointestinal 2 (1.2) mechanical ventilation yes 56 (43.1) no 74 (56.9) septic shock yes 28 (26.9) no 76 (73.1) 30-day mortality yes 106 (63.1) no 62 (36.9) meds score 1 31 (18.5) 2 25 (14.9) 3 62 (36.9) 4 33 (19.6) 5 17 (10.1) data are presented as mean ± standard deviation or number (%). there is missing data in some variables. gcs: glasgow coma scale. 0.426, p=0.025) showed a significant correlation with mean serum vitamin d level. sepsis patients with older age and those who died had a lower level of vitamin d. area under the roc curve of vitamin d regarding 1-month mortality of the sepsis patients was 0.701 (95%ci: 0.439 – 0.964) (figure 1). patients whose vitamin d level was less than 25 ng/ml were significantly more at risk of death (p=0.016). relative risk of mortality in patients with a vitamin d level less than 25 ng/ml was estimated to be 1.42 (95%ci: 1.0271.970). 4. discussion based on the results of the present study, the prevalence of vitamin d deficiency among sepsis patients presenting to the figure 1: area under the curve of serum level of vitamin d and 1month mortality of the sepsis patients presenting to emergency department. ed was estimated as 61.6%. a significant indirect correlation was observed between the serum level of vitamin d and mortality as well as older age. in line with the present study, previous studies have suggested that vitamin d concentration correlates with the rate of mortality in patients (4-6). in the study by parekh et al. there was a significant correlation between mean serum level of vitamin d in patients with sepsis who died and those who survived (18). the results of a study by rech et al. showed that vitamin d deficiency in patients with severe sepsis or septic shock was significantly associated with increase in 30-day mortality (6). in the study by nguyen et al. also low serum level of vitamin d was considered related to increase in 23-day mortality among 91 patients with sepsis (5). in arnson et al. study the correlation between vitamin d deficiency and mortality rate was confirmed in critically ill patients (11). in 2399 patients, vitamin d deficiency from 365 days before hospitalization was reported as a reliable predictor for both short term and long term mortality and positive blood culture for microorganism growth (19). the correlation between sufficient vitamin d and reduced mortality has not been reported in all studies (13, 14). in one study, the rate of mortality in sepsis patients correlated with vitamin d level upon admission, but this correlation was not significant (20). based on the national health and nutrition examination survey, level of 25-hydroxy vitamin d had an inverse correlation with occurrence of upper respiratory tract infection (21). the evidence is also indicative of the effect of vitamin d level on influenza and invasive pneumococcal disease (22). two meta-analyses performed on observational studies have confirmed that there is a significant correlation between vitamin d status and risk of being affected with sepsis, infection severity and 30-day mortality (23, 24). an important limitathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shojaei et al. 4 table 2: laboratory findings of studied patients variable mean ± sd ph 7.38 ± 0.08 hco3 (meq/l) 23.81 ± 6.58 paco2 (mmhg) 38.52 ± 11.51 hemoglobin (g/dl) 11.02 ± 2.21 hematocrit (%) 34.21 ± 7.90 white blood cell (109 /l) 12256.46 ± 8597.33 platelet count (109 /l) 234675.67 ± 136736.51 polymorphonuclear (%) 80.62 ± 8.33 blood urea nitrogen (mg/dl) 81.59 ± 47.09 creatinine (mg/dl) 1.49 ± 1.26 aspartate aminotransferase (u/l) 44.61 ± 89.99 alanine aminotransferase (u/l) 53.77 ± 109.80 alkaline phosphatase (u/l) 266.41 ± 134.47 bilirubin total (mg/dl) 0.77 ± 0.40 bilirubin direct (mg/dl) 0.34 ± 0.28 vitamin d3 (ng/ml) 19.03 ± 13.08 c-reactive protein (mg/dl) 66.69 ± 28.57 sd: standard deviation. tion present in all observational studies is also present in our study and it is not known if vitamin d deficiency is a marker for sepsis or if it causes sepsis, in other words if vitamin d deficiency is the cause for sepsis or its effect. in an experimental study on mice the causality of vitamin d as the reason for mortality in sepsis was evaluated. the findings of this experimental study showed that imposing vitamin d deficiency on the mice through their diet led to sepsis and increase in inflammation and cellular disorders and bacterial growth as well as disturbing the balance of apoptotic neutrophil aggregation. these experimental studies support the hypothesis that vitamin d deficiency might be a major cause in manifestation of sepsis (18, 25). it seems that with all the present evidence, consumption of vitamin d supplement might be able to reduce infection, sepsis and mortality caused by it, especially in older ages. 5. limitation controlling all the probable confounding factors in observational studies such as the present one is not possible and this can affect the findings of the study. in addition, this study was a single centered one with a relatively small sample size, which makes data generalization hard. another limitation of the study was that some data affecting the level of vitamin d such as cytokine level could not be recorded. 6. conclusion based on the results of the present study, the prevalence of vitamin d deficiency in sepsis patients presenting to the ed was estimated as 61.6%. a significant and indirect correlation was found between the serum level of vitamin d and mortaltable 3: relationship between mean serum vitamin d3 level and different factors variable vitamin d3 p sex male 18.67 ± 13.62 0.726 female 19.43 ± 12.54 age (year) 40 – 60 14.44 ± 7.08 0.037 ≥ 60 20.18 ± 14.40 30-day mortality yes 17.4 ± 9.9 0.025 no 21.4 ± 11.5 source of infection pneumonia 20.3 ± 13.0 urinary tract infection (ui) 18.1 ± 17.0 pneumonia + ui 18.1 ± 9.4 0.825 bed sore 18.1 ± 10.1 others 18.3 ± 3.4 meds score 1 18.9 ± 7.7 2 21.6 ± 11.2 3 18.4 ± 11.7 0.642 4 18.8 ± 11.5 5 16.7 ± 8.8 septic shock yes 21.53± 4.70 0.375 no 18.83 ± 12.87 mechanical ventilation yes 20.09 ± 15.73 0.428 no 18.01 ± 12.71 acute renal failure (cr>1.6 mg/dl) yes 21.92 ± 18.20 0.109 no 17.95 ± 10.66 liver failure (ast>45 u/l) yes 20.07 ± 15.87 0.613 no 18.66 ± 12.86 meds: mortality in emergency department sepsis. ity as well as older age. it seems that consumption of vitamin d supplements might be helpful in decreasing the prevalence of infection, sepsis, and mortality caused by it, especially in older age. 7. appendix 7.1. acknowledgements the staff of emergency department and laboratory of imam hossein hospital are thanked for their cooperation in carrying out this project. this article is derived from the thesis of dr. helia valaei to achieve her specialist degree in emergency medicine. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e1 authors orcids majid shojaei: 0000-0001-6819-9237 7.3. funding/support all the expenses of this research were paid by the researchers. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. lever a, mackenzie i. sepsis: definition, epidemiology, and diagnosis. bmj. 2007;335(7625):879-83. 2. jawad i, luksic i, rafnsson sb. assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. journal of global health. 2012;2(1). 3. fleischmann c, scherag a, adhikari nk, hartog cs, tsaganos t, schlattmann p, et al. assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. american journal of respiratory and critical care medicine. 2016;193(3):259-72. 4. jones b, heldwein k, means t, saukkonen j, fenton m. differential roles of toll-like receptors in the elicitation of proinflammatory responses by macrophages. annals of the rheumatic diseases. 2001;60(suppl 3):iii6-iii12. 5. nguyen hb, eshete b, lau kw, sai a, villarin m, baylink d. serum 1, 25-dihydroxyvitamin d: an outcome prognosticator in human sepsis. plos one. 2013;8(5):e64348. 6. rech ma, hunsaker t, rodriguez j. deficiency in 25hydroxyvitamin d and 30-day mortality in patients with severe sepsis and septic shock. american journal of critical care. 2014;23(5):e72-e9. 7. liu pt, stenger s, tang dh, modlin rl. cutting edge: vitamin d-mediated human antimicrobial activity against mycobacterium tuberculosis is dependent on the induction of cathelicidin. the journal of immunology. 2007;179(4):2060-3. 8. reiter rj, acuna-castroviejo d, tan dx, burkhardt s. free radical-mediated molecular damage. annals of the new york academy of sciences. 2001;939(1):200-15. 9. aranow c. vitamin d and the immune system. journal of investigative medicine. 2011;59(6):881-6. 10. cannell j, vieth r, umhau j, holick m, grant w, madronich s, et al. epidemic influenza and vitamin d. epidemiology & infection. 2006;134(6):1129-40. 11. arnson y, gringauz i, itzhaky d, amital h. vitamin d deficiency is associated with poor outcomes and increased mortality in severely ill patients. qjm: an international journal of medicine. 2012;105(7):633-9. 12. autier p, gandini s. vitamin d supplementation and total mortality: a meta-analysis of randomized controlled trials. archives of internal medicine. 2007;167(16):1730-7. 13. higgins dm, wischmeyer pe, queensland km, sillau sh, sufit aj, heyland dk. relationship of vitamin d deficiency to clinical outcomes in critically ill patients. journal of parenteral and enteral nutrition. 2012;36(6):71320. 14. flynn l, zimmerman lh, mcnorton k, dolman m, tyburski j, baylor a, et al. effects of vitamin d deficiency in critically ill surgical patients. the american journal of surgery. 2012;203(3):379-82. 15. heshmat r, mohammad k, majdzadeh s, forouzanfar m, bahrami a, ranjbar omrani g. vitamin d deficiency in iran: a multi-center study among different urban areas. iran j public health. 2008;37(suppl). 16. bassir m, laborie s, lapillonne a, claris o, chappuis mc, salle b. vitamin d deficiency in iranian mothers and their neonates: a pilot study. acta paediatrica. 2001;90(5):577-9. 17. davies m, hagen po. systemic inflammatory response syndrome. british journal of surgery. 1997;84(7):920-35. 18. parekh d, patel jm, scott a, lax s, dancer rc, d’souza v, et al. vitamin d deficiency in human and murine sepsis. critical care medicine. 2017;45(2):282. 19. braun a, chang d, mahadevappa k, gibbons fk, liu y, giovannucci e, et al. association of low serum 25hydroxyvitamin d levels and mortality in the critically ill. critical care medicine. 2011;39(4):671. 20. cecchi a, bonizzoli m, douar s, mangini m, paladini s, gazzini b, et al. vitamin d deficiency in septic patients at icu admission is not a mortality predictor. minerva anestesiologica. 2011;77(12):1184-9. 21. ginde aa, mansbach jm, camargo ca. association between serum 25-hydroxyvitamin d level and upper respiratory tract infection in the third national health and nutrition examination survey. archives of internal medicine. 2009;169(4):384-90. 22. white an, ng v, spain cv, johnson cc, kinlin lm, fisman dn. let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in philadelphia, pennsylvania. bmc infectious diseases. 2009;9(1):196. 23. upala s, sanguankeo a, permpalung n. significant association between vitamin d deficiency and sepsis: a systematic review and meta-analysis. bmc anesthesiology. 2015;15(1):84. 24. moromizato t, litonjua aa, braun ab, gibbons fk, giovannucci e, christopher kb. association of low serum 25hydroxyvitamin d levels and sepsis in the critically ill. critical care medicine. 2014;42(1):97-107. 25. moller s, laigaard f, olgaard k, hemmingsen c. effect of 1, 25-dihydroxy-vitamin d3 in experimental sepsis. interthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. shojaei et al. 6 national journal of medical sciences. 2007;4(4):190. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e28 rev i ew art i c l e late complications of covid-19; an umbrella review on current systematic reviews seyedahmad seyedalinaghi1, amirbehzad bagheri2, armin razi3, paniz mojdeganlou4, hengameh mojdeganlou5, amir masoud afsah6, arian afzalian3, parinaz paranjkhoo7, ramin shahidi8, pegah mirzapour1, zahra pashaei1, mohammad amin habibi9, parmida shahbazi10, sahar nooralioghli parikhani3, narjes sadat farizani gohari11, yusuf popoola12, esmaeil mehraeen13∗, daniel hackett14 1. iranian research center for hiv/aids, iranian institute for reduction of high risk behaviors, tehran university of medical sciences, tehran, iran. 2. interdisciplinary consortium on advanced motion performance, division of vascular surgery and endovascular therapy, michael e. debakey department of surgery, baylor college of medicine, houston, texas. 3. school of medicine, tehran university of medical sciences, tehran, iran. 4. shahid beheshti university of medical sciences, tehran, iran. 5. department of pathology, the johns hopkins university school of medicine, baltimore, md, usa. 6. department of radiology, school of medicine, university of california, san diego (ucsd), california, usa. 7. turpanjian college of health sciences, american university of armenia, yerevan 0019, armenia. 8. school of medicine, bushehr university of medical sciences, bushehr, iran. 9. clinical research development center, qom university of medical sciences, qom, iran. 10.orthopedic department, orthopedic surgery research center (osrc), sina hospital, tehran university of medical sciences, tehran, iran. 11.school of medicine, shahid sadoughi university of medical sciences, yazd, iran. 12.health information management unit, department of computer science, adeleke university, ede, nigeria. 13.department of health information technology, khalkhal university of medical sciences, khalkhal, iran. 14.physical activity, lifestyle, ageing and wellbeing faculty research group, school of health sciences, faculty of medicine and health, the university of sydney, sydney, new south wales, australia. received: january 2023; accepted: february 2023; published online: 12 march 2023 abstract: introduction: several clinical manifestations have been discovered for covid-19 since the emergence of sars-cov-2, which can be classified into early, medium, and long-term complications. however, late complications can be present after recovery from acute covid-19 illness. the present study aims to comprehensively review the available evidence of late complications related to covid-19. methods: a search was conducted, using keywords, through electronic databases, which included scopus, web of science, pubmed, and embase up to august 29, 2022. study selection was performed according to a strict inclusion and exclusion criteria. the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist was followed, and studies were appraised using the national institute of health (nih) quality assessment and risk of bias tool. results: in total, 50 studies were included, and nine distinct covid-19 late complication categories were identified. a review of these studies revealed that neurologic and psychiatric (n=41), respiratory (n=27), musculoskeletal and rheumatologic (n=22), cardiovascular (n=9), and hepatic and gastrointestinal (n=6) complications were the most prevalent complications of long covid-19. conclusion: almost all human body systems are affected by late complications of covid-19 with different severity and prevalence. fatigue and some other neuropsychiatric symptoms are the most common late complications among long covid-19 patients. respiratory symptoms including dyspnea (during exercise), cough, and chest tightness were the next most prevalent long-term complications of covid-19. since these complications are persistent and late, being aware of the signs and symptoms is essential for the healthcare providers and patients. keywords: covid-19; sars-cov-2; post-acute covid-19 syndrome; patient outcome assessment cite this article as: seyedalinaghi sa, bagheri ab, razi a, mojdeganlou p, mojdeganlou h, et al. late complications of covid-19; an umbrella review on current systematic reviews. arch acad emerg med. 2023; 11(1): e28. https://doi.org/10.22037/aaem.v11i1.1907. ∗corresponding author: esmaeil mehraeen, department of health information technology, khalkhal university of medical sciences, khalkhal, iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 2 1. introduction in relation to the groundbreaking emergence of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) in late december 2019, several concepts were presented regarding the clinical aspects of covid-19 caused by sars-cov-2 (1, 2). sars-cov-2 uses angiotensin-converting enzyme 2 (ace2) receptors to invade the host cells (3). due to the widespread expression of ace2 in human organs, covid-19 can present with different clinical manifestations, including pneumonia, myocarditis, cardiac infarction, kidney injuries, neurologic manifestations, gastrointestinal disorders, etc. (4). sarscov-2 is still spreading worldwide, and growing evidence reports the de novo manifestations of covid-19. the duration of symptoms of covid-19 is not fully understood and the complications of covid-19 present in different timelines and can be categorized into early (5), medium (6), and late (7) manifestations after covid-19 infection. manifestations and clinical and para-clinical indicators remaining different from healthy baseline level days to months after covid-19 infection are considered post-covid-19 complications (8). according to national institute for health and care excellence (nice), post-covid-19 infection is characterized by manifestations that are sustained for more than 12 weeks after covid-19 infection, and other diagnoses cannot be made for such complications (9). although the majority of complications arise from the onset of covid-19, a body of evidence reported the late complications related to covid-19, which are present in the survivors of covid-19 several weeks to months after the elimination of sars-cov-2, which can be attributed to the indirect damage of organs. some pathways, including immune dysregulation, coagulopathy, and endothelial damage are introduced for late complications of covid-19 (10). consequently, it was shown that almost all human body systems are affected by covid-19 and can show late complications. however, the percentage, severity, and duration of such late manifestations are different. additionally, late complications are associated with an abnormal level of some laboratory parameters such as inflammatory and anti-inflammatory parameters that can indicate organ dysfunction (11, 12). several systematic reviews and meta-analyses documented the late complications of covid-19, including a broad range of organ injuries. in this umbrella review, we sought to provide comprehensive evidence on the late complications of covid-19 to improve the clinical insight of physicians and postal code: 5681761351, tel: +98-45-32426801, fax: +98-45-32422305, e-mail: es.mehraeen@gmail.com, orcid: https://orcid.org/0000-0003-4108-2973. summarize the post-covid-19 complications and highlight the importance of follow-up in patients with covid-19. 2. methods in this study we comprehensively reviewed current systematic review studies about late and long-term complications of covid-19. to optimize validity and authenticity, we utilized items of the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist. studies were appraised using the national institute of health (nih) quality assessment and risk of bias tool. 2.1. data sources an extensive search of four online databases was performed, which included web of science, pubmed, scopus, and embase. articles were restricted to english language and the search was conducted up to august 29, 2022. the following is the search strategy we have used on pubmed database, whereas search strategies for other databases are provided in supplemental material 1. ("covid-19" [mesh] or "sars-cov-2" [mesh] or covid19 [tiab] or sars-cov-2 [tiab] or coronavirus disease 2019 [tiab] or severe acute respiratory syndrome coronavirus 2 [tiab]) and (long-term outcome*[tiab] or long-term complication*[tiab] or late complication*[tiab] or chronic complication*[tiab] or long-term effect*[tiab] or longterm impact*[tiab] or consequence*[tiab] or sequelae [tiab] or long covid [tiab] or sequel [tiab] or post-acute covid syndrome [tiab] or long-covid [tiab] or post-acute covid19 syndrome [tiab]) and (systematic review [tiab] or meta-analysis [tiab]). besides searching through databases, several journals were searched in a manual search. 2.2. study selection to improve the study selection process, a two-step method was employed. two researchers screened articles with regard to titles and abstracts. the second step involved screening of full texts that were potentially eligible. articles that met the inclusion/ exclusion criteria were advanced to the next step of data extraction. in other words, articles were included if they had a systematic review nature, were peer-reviewed, and assessed long-term complications of covid-19. on the other hand, studies were excluded if they were non-human research studies, lacking the required data, duplications, narrative reviews, umbrella reviews, abstracts with deficient full texts, preprint articles, editorial letters, conference abstracts, case series, and case reports. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e28 2.3. data extraction four researchers were involved in extraction of data from articles that met the eligibility criteria. a preformatted spreadsheet was used to gather the extracted data. potential complications of long covid-19 were categorized into the following nine groups: cardiovascular, renal, hepatic and gastrointestinal, respiratory, neurologic and psychiatric, musculoskeletal and rheumatologic, stroke, ocular, thrombosis, and embolism. information concerning late complication assessment methods, late complication onset, and time of recovery from sequelae was also extracted. any duplicates were removed, and the accuracy of the extracted data was checked. 2.4. quality and bias risk assessment the quality and authenticity of the selected articles, as stated before, were evaluated by conforming to the prisma checklist. we also addressed bias risk by utilizing national institute of health (nih) questionnaire for quality assessment. table 1 illustrates the application of this tool to our study. each study was assessed and rated by two independent researchers. last two columns show their ratings of individual papers. details of this questionnaire are available at the bottom of this table. 3. results the database search yielded 727 potential studies (after removing duplicates), and following the screening and quality control according to nih quality assessment tool (table 1), a total of 50 articles met the inclusion criteria (figure 1). the included studies were carried out in an extensive range of countries including usa (n=9), uk (n=8), italy (n=4), canada (n=3), china (n=3), australia (n=2), germany (n=2), ireland (n=2), saudi arabia (n=2), spain (n=2), and switzerland (n=2). the following countries were each subject to one study: brazil, denmark, india, indonesia, iran, iraq, mexico, pakistan, south africa, and uae. in total 1,833 studies were included in our enrolled systematic reviews, and they had included a total of 5,425,998 covid-19 patients. two studies were conducted on children (103,212 children and adolescent covid-19 patients), and the remaining 48 papers were carried out on adults. in regard to level of evidence, 19 studies were meta-analyses and had quantitative synthesis while, the remaining 31 studies were systematic reviews, two of which were conducted involving case-reports and case-series and 29 studies had included case-control, cross-sectional, and cohort studies in their qualitative synthesis. review of included studies demonstrated that neurologic and psychiatric (n=41), respiratory (n=27), musculoskeletal and rheumatologic (n=22), cardiovascular (n=9), and hepatic and gastrointestinal (n=6) complications were the most prevalent complications of long covid-19. moreover, renal, ocular, and stroke sequelae were also reported by a few studies (n=2 for each sequela). there was one study that reported thrombosis or embolism as a complication of long covid19. finally, the onset of complications ranged between 10 days up to 13 months. the thorough details of included studies are provided in table 2. 4. discussion almost all human body systems are affected by late complications of covid-19 with different severities and prevalences. this systematic umbrella review found that late complications of long covid-19 infection could be classified into nine groups. a discussion of each of these groups is covered below. neurologic and psychiatric it seems that late neurologic and psychiatric manifestations of the covid-19 infection are the main and most prevalent features of this disease, and fatigue is the most prevalent symptom in long-covid patients. premraj l et al., (13) reviewed 18 studies and more than 10000 covid-19 patients. they concluded that some late covid-19 manifestations may last for more than 3 months after infection. these symptoms include psychiatric symptoms such as fatigue, cognitive impairment (memory problems, attention deficit), and sleep disorders. these symptoms and others like depression, post-traumatic stress disorder (ptsd), anxiety, anger, fear, dizziness, and mood change were reported in most studies (7, 13-46). however, covid-19 severity in the acute phase of the infection was not correlated with increased symptoms in the post-acute phase of covid-19 (47). there was some evidence inferring that identification of the long-term psychological consequences during the pandemic is critical to ensuring proper care provision (18, 48). neurologic manifestations like headache, myelitis, neuropathies, paresthesia, parkinsonism, cogwheel rigidity (49), optic neuritis, altered smell, olfactory dysfunction (anosmia, ageusia), encephalitis (50), epilepsy, bell’s palsy, and myoclonus were also reported in some studies. guillain-barre syndrome was the most prevalent neurological condition of long covid-19 reported in the study by ahmed jo et al. (50). headache was also one of the common symptoms of long covid-19 during the first six months after recovery in the study by fernández-de-las-peñas, césar et al. (51). respiratory the lung is the most commonly affected organ in acute severe covid-19 infection and its involvement is not unusual in long-term covid-19. some patients reported shortness of breath, cough, and chest tightness during the post-covid19 phase for an extended period of time. dyspnea usually worsens with increased physical exertion such as during exthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 4 ercise. treatment has not been very effective in eliminating these symptoms, but the intensity of the symptoms usually reduces over time. some studies like the one by so et al., (52) showed that the radiographic feature was ground glass opacity (44%) and parenchymal band or fibrous stripe (33.9%). restrictive (16%) and obstructive (8%) patterns were also reported in their systematic review. these abnormalities lasted for a long period of time (15, 53). musculoskeletal and rheumatologic as mentioned in the studies by pinzon rt et al. (14) and salamanna f et al. (29), manifestations like musculoskeletal, joint, and body pain have also been reported among long covid-19 sufferers. gracia-ramos et al., (54) studied 90 systematic reviews and reported that vasculitis, including small, medium and large vasculitis, have been seen among long covid-19 patients. inflammatory myopathies, systemic lupus erythematosus (sle), sarcoidosis, and arthritis were also reported. cutaneous vasculitis following covid-19 is usually resistant to treatment and subsides over time. cardiovascular the heart can also be involved in long covid-19. alosaimi et al. (55) concluded that the late cardiac involvements are pericardial effusion, myocarditis, pericarditis, elevated troponin levels, and myocardial edema. ramadan et al. (56) reviewed 35 studies in relation to cardiac involvement in long covid-19. chest pain, dyspnea, and palpitations were usually reported by these patients. t-wave changes, st-segment elevation/depression, and right bundle branch block were seen in the electrocardiogram (ecg) of these patients. using echocardiography, there are reports of reduced left ventricular ejection fraction, pericardial effusion, global hypokinesis, left ventricular hypertrophy, diastolic dysfunction, and pulmonary hypertension. the researchers concluded that increased t1 intensity, late gadolinium enhancement, increased t2 intensity, pericardial effusion, decreased global longitudinal strain, decreased left ventricular ejection fraction, myocardial enhancement, pericardial enhancement, myocarditis, myopericarditis, pericarditis, and myocardial infarction may be seen in the cardiac magnetic resonance imaging (mri) of these patients. other reported cardiac involvements in long covid-19 were elevated nt-pro-bnp levels, and arterial occlusion (in angiogram). patients with long covid-19 were more susceptible to heart failure, myocardial infarction, stroke, and arrhythmia. hepatic and gastrointestinal choudhury et al. (57) studied 50 systematic reviews. this research reported that long covid-19 patients were more susceptible to complaints of gastrointestinal manifestations like loss of appetite, dyspepsia, constipation, loss of taste, irritable bowel syndrome (ibs), abdominal pain, diarrhea, and nausea/vomiting. renal urinary problems including urinary tract infections are rare but may be seen among long covid-19 patients (40, 58). ocular ophthalmologic problems among long covid-19 patients, including conjunctivitis, dry eye, trouble seeing/blurred vision, photophobia, sore eyes, and pain were rarely reported (54, 59). thrombosis or embolism and stroke seyedalinaghi et al. (40) reviewed 65 studies. they concluded that venous/arterial thrombosis and cardiac/brain stroke may also be seen among long covid-19 patients. others other late and less common complications of covid-19 include sputum/nasal congestion, hyperhidrosis, rhinorrhea, cough, myalgia/arthralgia, body weight changes, otalgia, sore throat, variations in heart rate, dysphonia, fever palpitations, hair loss, dysphagia, speech disturbances, hypoproteinemia and menstrual problems. 5. conclusion covid-19 patients may have late and chronic manifestations. these symptoms are known as long covid-19 and can last for more than 6 months. additionally, long covid19 is usually resistant to treatment but may resolve over time. fatigue and other neuropsychiatric symptoms are the most common late complications among patients with long covid-19. respiratory symptoms including dyspnea (during exercise), cough, and chest tightness were the next most prevalent long-term complications of covid-19. since these complications are persistent and late, being aware of the signs and symptoms is essential for the health care providers and patients. 6. declarations 6.1. acknowledgments the present study was conducted in collaboration with khalkhal university of medical sciences, iranian research center for hiv/aids, tehran university of medical sciences, and the university of sydney. 6.2. conflict of interest the authors declare that there is no conflict of interest regarding the publication of this manuscript. 6.3. fundings and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e28 6.4. authors’ contribution (1) the conception and design of the study: esmaeil mehraeen, seyedahmad seyedalinaghi (2) acquisition of data: amirbehzad bagheri, armin razi, hengameh mojdeganlou, paniz mojdeganlou (3) analysis and interpretation of data: amir masoud afsahi, arian afzalian (4) drafting the article: esmaeil mehraeen, parinaz paranjkhoo, ramin shahidi, pegah mirzapour, zahra pashaei, mohammad amin habibi, parmida shahbazi, sahar nooralioghli parikhani, narjes sadat farizani gohari, yusuf popoola (5) revising it critically for important intellectual content: seyedahmad seyedalinaghi, daniel hackett (6) final approval of the version to be submitted: seyedahmad seyedalinaghi, esmaeil mehraeen, daniel hackett final version was read and approved by all author. 6.5. ethics approval and consent to participate not applicable 6.6. consent to publication not applicable 6.7. availability of data and material the authors stated that all information provided in this article could be shared. references 1. mehraeen e, oliaei s, seyedalinaghi s, karimi a, mirzapour p, 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martimbianco al, pacheco rl, bagattini âm, riera r. frequency, signs and symptoms, and criteria adopted for long covid-19: a systematic review. int j clin pract. 2021;75(10):e14357. 45. sanchez-ramirez dc, normand k, zhaoyun y, torrescastro r. long-term impact of covid-19: a systematic review of the literature and meta-analysis. biomedicines. 2021;9(8):900. 46. sandler cx, wyller vbb, moss-morris r, buchwald d, crawley e, hautvast j, katz bz, knoop h, little p, taylor r, wensaas ka, lloyd ar. long covid and post-infective fatigue syndrome: a review. open forum infect dis. 2021 sep 9;8(10):ofab440. doi: 10.1093/ofid/ofab440. pmid: 34631916; pmcid: pmc8496765. 47. renaud-charest o, lui lm, eskander s, ceban f, ho r, di vincenzo jd, et al. onset and frequency of depression in post-covid-19 syndrome: a systematic review. j psychiatr res. 2021;144:129-37. 48. zürcher sj, banzer c, adamus c, lehmann ai, richter d, kerksieck p. post-viral mental health sequelae in infected persons associated with covid-19 and previous epidemics and pandemics: systematic review and meta-analysis of prevalence estimates. j infect public health. 2022 may;15(5):599-608. doi: 10.1016/j.jiph.2022.04.005. epub 2022 apr 20. pmid: 35490117; pmcid: pmc9020842. 49. mehraeen e, dadras o, afsahi am, karimi a, pour mm, mirzapour p, et al. vaccines for covid-19: a systematic review of feasibility and effectiveness. infect disord drug targets. 2022;22(2):e230921196758. 50. ahmed jo, ahmad sa, hassan mn, kakamad fh, salih rq, abdulla ba, rahim fattah fh, mohammed sh, ali rk, salih am. post covid-19 neurological complications; a meta-analysis. ann med surg (lond). 2022 apr;76:103440. doi: 10.1016/j.amsu.2022.103440. epub 2022 mar 3. pmid: 35261766; pmcid: pmc8891214. 51. fernández-de-las-peñas c, navarro-santana m, gómezmayordomo v, cuadrado ml, garcía-azorín d, arendtnielsen l, et al. headache as an acute and post-covid19 symptom in covid-19 survivors: a meta-analysis of the current literature. eur j 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recovery: a systematic review. clin microbiol infect. 2021;27(9):1250-61. 57. choudhury a, tariq r, jena a, vesely ek, singh s, khanna s, et al. gastrointestinal manifestations of long covid: a systematic review and meta-analysis. therap adv gastroenterol. 2022;15:17562848221118403. 58. lopez-leon s, wegman-ostrosky t, ayuzo del valle nc, perelman c, sepulveda r, rebolledo pa, et al. longcovid in children and adolescents: a systematic review this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 8 and meta-analyses. sci rep. 2022;12(1):9950. 59. behnood sa, shafran r, bennett sd, zhang axd, o’mahoney ll, stephenson tj, et al. persistent symptoms following sars-cov-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies. j infect. 2022;84(2):158-70. 60. de luca p, di stadio a, colacurcio v, marra p, scarpa a, ricciardiello f, et al. long covid, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence. acta otorhinolaryngol ital. 2022;42(suppl 1):s87. 61. ali ss, mumtaz a, qamar ma, tebha ss, parhin a, butt m, essar my. new-onset parkinsonism as a covid19 infection sequela: a systematic review and metaanalysis. ann med surg (lond). 2022 aug;80:104281. doi: 10.1016/j.amsu.2022.104281. epub 2022 aug 8. pmid: 35971509; pmcid: pmc9359766. 62. willi s, lüthold r, hunt a, hänggi nv, sejdiu d, scaff c, et al. covid-19 sequelae in adults aged less than 50 years: a systematic review. travel med infect dis. 2021;40:101995. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e28 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) 2020 flow diagram of study retrieval process. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 10 table 1: quality ratings of included studies in accordance with nih quality assessment tool first autor *question rating by reviewers 1 2 3 4 5 6 7 8 9 #1 #2 fernández-de-las-peñas c (51) yes yes cd cd na yes cd yes yes fair fair de luca p (60) yes yes cd na na yes cd yes yes fair fair ahmed jo (50) yes yes cd na na yes cd yes yes fair fair ali ss (61) yes yes na cd na yes cd na yes fair fair premraj l (13) yes yes cd cd na yes cd yes yes fair fair pinzon rt (14) yes yes na cd na yes cd yes yes fair fair so m (52) yes yes cd na na yes cd yes yes fair fair long q, li j (15) yes yes cd cd na yes cd yes yes fair fair patria yn (53) yes yes na na na yes cd yes yes fair fair vanderlind wm (16) yes yes nr na na yes cd yes yes fair fair renaud-charest o (47) yes yes na na na yes cd na yes fair fair schou tm (17) yes yes na cd na yes cd na yes fair fair arora t (18) yes yes cd cd na yes cd yes yes fair fair zürcher sj (48) yes yes na cd na yes cd yes yes fair fair bourmistrova nw (20) yes yes cd cd na yes cd yes yes fair fair badenoch jb (19) yes yes cd cd na yes cd yes yes fair fair khraisat b (21) yes yes nr cd na yes cd yes yes fair fair alosaimi b (55) yes yes na na na yes cd yes yes fair fair ramadan ms (56) yes yes na cd na yes cd yes yes fair fair choudhury a (57) yes yes cd na na yes cd yes yes fair fair gracia-ramos ae (54) yes yes cd na na yes cd yes yes fair fair behnood sa (59) yes yes cd cd na yes cd yes yes fair fair lopez-leon s (58) yes yes na na na yes cd yes yes fair fair ahmed h (22) yes yes cd cd na yes cd yes yes fair fair alkodaymi ms (23) yes yes nr cd na yes cd na yes fair fair ceban f (24) yes yes cd cd na yes cd yes yes fair fair chen c, haupert sr (25) yes yes na na na yes cd yes yes fair fair fernández-de-las-peñas c (26) yes yes na na na yes cd yes yes fair fair lopez-leon s (7) yes yes cd cd na yes cd yes yes fair fair michelen m (27) yes yes cd cd na yes cd yes yes fair fair nguyen nn (28) yes yes na cd na yes cd yes yes fair fair salamanna f (29) yes yes na cd na yes cd yes yes fair fair sandra willi (62) yes yes nr na na yes cd yes yes fair fair yang t (30) yes yes nr cd na yes cd yes yes fair fair zeng n (31) yes yes cd cd na yes cd yes yes fair fair almas t (32) yes yes na na na yes cd yes yes fair fair ahmad ms (33) yes yes cd cd na yes cd yes yes fair fair healey q (34) yes yes cd na na yes cd yes yes fair fair d’ettorre g (35) yes yes na na na yes cd yes yes fair fair groff d (36) yes yes na na na yes cd yes yes fair fair han q (37) yes yes na cd na yes cd yes yes fair fair iwu cj (38) yes yes cd cd na yes cd yes yes fair fair iqbal fm (39) yes yes cd cd na yes cd yes yes fair fair seyedalinaghi s (40) yes yes cd cd na yes cd yes yes fair fair jennings g (41) yes yes cd na na yes cd yes yes fair fair ma y (42) yes yes nr cd na yes cd yes yes fair fair malik p (43) yes yes na cd na yes cd yes yes fair fair cabrera martimbianco al (44) yes yes na cd na yes cd yes yes fair fair sanchez-ramirez dc (45) yes yes cd cd na yes cd na yes fair fair sandler cx (46) yes yes cd na na yes cd yes yes fair fair nih = national institutes of health; cd = cannot determine; nr = not reported; na = not applicable. *the nih quality assessment tool for case series studies (https://www.nhlbi.nih.gov/health-topics/studyquality-assessment-tools) contains nine questions: 1 = was the study question or objective clearly stated?, 2 = was the study population clearly and fully described, including a case definition?, 3 = were the cases consecutive?, 4 = were the subjects comparable?, 5 = was the intervention clearly described?, 6 = were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?, 7 = was the length of follow-up adequate?, 8 = were the statistical methods well-described?, 9 = were the results well-described? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e28 table 2: characteristics of 50 included studied in the umbrella review f irst a u th o r a n d c o u n try in clu d ed stu d ies s tu d y p o p u la tio n late complication c o m p lica tio n a ssessm en t m eth o d s t im e o f la te co m p lica tio n o n set t im e o f reco very fro m m en tio n ed s eq u ela e l a te co m p lica tio n s c a rd io va scu la r r en a l h ep a tic a n d g a stro in testin a l r esp ira to ry n eu ro lo g ic a n d p sych ia tric m u scu lo sk eleta la n d r h eu m a to lo g ic s tro k e o cu la r t h ro m b o sis o r e m b o lism fernándezde-laspeñas c (51) spain 35 28, 438 * 47.1% at onset or hospital admission, 10.2% at 30 days, 16.5% at 60 days, 10.6% at 90 days, and 8.4% at ≥180 days after onset/hospital discharge post-covid headaches seems to be stable during the first 180 days. de luca p (60) italy 16 5582 * association between sars-cov-2 infection and persistent hearing or chemosensory problems in patients with covid-19 ahmed jo (50) iraq 40 55 * * average interval between covid-19 infection to the onset of neurological sequelae was 33.2 days. guillain-barre syndrome was the most commonly reported neurological condition. transverse myelitis, critical illness neuromyopathy/neuropathy, encephalopathy, parkinsonism, optic neuritis, status epilepticus, encephalitis, bell’s palsy, vestibulocochlear neuritis, opsoclonus myoclonus syndrome, and myopathy were also reported. ali ss (61) pakistan 10 13 * magnetic resonance imaging (mri): 6(46.2%) cases, electroencephalography (eeg): 3(23.1%) cases, fluorodeoxyglucose (fdg): 3(23.1%) cases, positron emission tomography (pet): 3(23.1%) cases. cogwheel rigidity was the most common symptom of parkinsonism in patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 12 table 2: characteristics of 50 included studied in the umbrella review premraj l (13) australia 18 10, 530 * 3 or more months postinfection fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder), and psychiatric manifestations (sleep disturbances, anxiety, and depression) pinzon rt (14) indonesia 36 9944 * chest ct: 13 studies, pulmonary function test (pft): 10 studies during the first six months after the onset of illness fatiguecognitive disorder; paresthesia; sleep disorder; musculoskeletal pain; and dizziness so m (52) usa 15 3066 * lung function pulmonary function tests (including spirometry, lung volume, and diffusion capacities): 20% (95% ci 13–17%) chest ct abnormalities: glass opacity in 44.1%, parenchymal band or fibrous stripe in 33.9%. abnormal pulmonary function test: 44.3%, impaired diffusion capacity 34.8%. restrictive and obstructive patterns:16.4% and 7.7%, respectively. long q, li j (15) china 16 4478 * fatigue, weakness, psychosocial symptoms, and abnormalities in lung function patria yn (53) indonesia 7 378 * lung function test: (77.56, 95% ci: 47.83–107.29) abnormal lung function for at least several weeks in the recovery period. vanderlind wm (16) usa 33 9676 * sleep difficulties, fatigue, anxiety, acute and posttraumatic stress, depression, self-reported cognitive functioning, psychiatric sequalae renaudcharest o (47) canada 8 1058 * the dsm-v criteria (n = 1),13-items beck’s depression inventory (bdi-13) (n = 2), zung self-rating depression scale (zsds) (n = 1), depression, anxiety and stress scale (dass-21) (n = 1), hospital anxiety and depression scale (hads) (n = 3), patient health questionnaire (phq-9) (n = 1), and quality of life in neurological disorders (neuro-qol) (n = 1). depressive symptoms this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e28 table 2: characteristics of 50 included studied in the umbrella review schou tm (17) denmark 6 751955 * anxiety and/or depression, post-traumatic stress disorder (ptsd), cognitive deficits, fatigue, and sleep disturbances arora t (18) uae 28 97173 * anxiety, ptsd, stress/distress, depression, anger, fear, worry, sleep quality/insomnia zürcher sj (48) switzerland 59 11248 * high zsds scores: (symbol coding test: wald = 8.37, p = 0.003), dass-21 depression scores (mini-mental state examination: β = – 0.039, p = 0.007), performance on tests assessing immediate recall in verbal memory (california verbal learning test: β = – 0.432, p = 0.016), visual reaction times (test of everyday attention: β = 6.298, p = 0.007), executive abilities (tower of london test: β = – 0.149, p = 0.008) and visuospatial abilities (rey figure copy and recall: β = – 0.096, p = 0.044). mental health problems bourmistrova nw (20) uk 33 4935 * sleep disturbances (primarily insomnia), ptsd, anxiety, and depression badenoch jb (19) uk 51 18917 * sleep problems and fatigue appear to affect roughly one-quarter of survivors. cognitive impairment, anxiety, post-traumatic symptoms, and depression are also common in the first 6 months. khraisat b (21) usa 27 9605 * ptsd, anxiety, psychological distress, depression, and sleeping disorders alosaimi b (55) saudi arabia 15 6229 * cardiac mri, ecg, echocardiography, cardiac enzyme (troponin i or t), and holter monitoring pericardial effusion, myocarditis, pericarditis, elevated troponin levels, and myocardial edema ramadan ms (56) italy 35 52, 609 * cardiac mri, echocardiography, troponin, questionnaires, n-terminal prob-type natriuretic peptide (nt-probnp), endomyocardial biopsy, 24-hour ecg, clinical assessment, coronary angiography, and registry analysis. 41 to 71 days cardiovascular findings in mri were: increased t1 intensity, late gadolinium enhancement, increased t2 intensity, pericardial effusion, decreased global longitudinal strain, decreased left ventricular ejection fraction, myocardial enhancement, pericardial enhancement, myocarditis, myopericarditis, pericarditis, and myocardial infarction as cardiac sequelae. studies using echocardiography reported reduced left ventricular ejection fraction, pericardial effusion, global hypokinesis, left ventricular hypertrophy, diastolic dysfunction, and pulmonary hypertension. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 14 table 2: characteristics of 50 included studied in the umbrella review ecg changes: t-wave changes, st segment elevation/depression, right bundle branch block, and sinus tachycardia. elevated troponin and nt-pro-bnp levels were also observed. angiography reports: two-vessel coronary artery disease including left anterior descending artery occlusion and left anterior descending artery occlusion. cardiac symptoms: chest pain, dyspnea, and palpitations, heart failure, myocardial infarction, stroke, and arrhythmia choudhury a (57) india 50 401, 289 * covid-19 patient follow-up time: from 4 weeks up to 8.4 months gastrointestinal (gi) symptoms among covid-19 patients was 12%, while, the overall frequency of gi symptoms among long-covid-19 patients was 22%. gi symptoms among severe cases of covid-19, was 13%, while this was 20% for long-covid-19 patients after severe covid-19 infection. gi symptoms: loss of appetite, dyspepsia, constipation, loss of taste, irritable bowel syndrome (ibs), abdominal pain, diarrhea, and nausea/vomiting graciaramos ae (54) mexico 90 99 cases of newonset rheumatic autoimmune diseases (rad) * organ biopsy, clinical criteria, immunologic blood tests, imaging modalities, synovial fluid analysis, electromyography, and muscle biopsy. 19 to 44 days. 46 new-onset vasculitis sorted by prevalence: small-vessel vasculitis, medium-vessel vasculitis, and large-vessel vasculitis 32 new-onset sorted by prevalence: spondylarthritis, reactive arthritis 9 new-onset inflammatory myopathies 6 new-onset systemic lupus erythematosus (sle) behnood sa (59) uk 22 23,141 children and young people * * * * from 28 to 324 days with median duration of 125 days fatigue, dyspnea, headache, cognitive difficulties, myalgia, abdominal pain, fever, loss of smell, cough, and diarrhea developing persistent symptoms: cognitive difficulties, headache, loss of smell, sore throat, and sore eyes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e28 table 2: characteristics of 50 included studied in the umbrella review lopezleon s (58) usa 21 80, 071 children and adolescents * * * * * * * from 1 to 13 months. general prevalence of long-covid-19 in children and adolescents was 25.24%. for hospitalized patients, the prevalence of long-covid-19 was 29.19%. mood changes, fatigue, sleep disorders, headache, respiratory symptoms, sputum/nasal congestion, cognition difficulties, loss of appetite, exercise intolerance, altered smell, hyperhidrosis, chest pain, dizziness, rhinorrhea, cough, myalgia/arthralgia, body weight changes, altered taste, otalgia, ophthalmologic problems, abdominal pain, dermatologic problems, sore throat, chest tightness, variations in heart rate, constipation, dysphonia, fever, diarrhea, vomiting, palpitations, hair loss, neurological abnormalities, urinary symptoms, dysphagia, and speech disturbances compared to controls, children with long-covid-19 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever. ahmed h (22) uk 28 2,854 * * * * sf-36 for health-related quality of life, george’s respiratory questionnaire (sgrq), chest ct up to 6 months after discharge post-traumatic stress disorder, depression, and anxiety were considerable beyond 6 months after discharge. alkodaymi ms (23) usa 63 257, 348 * physical assessment, icd-10 codes, electronic medical records 3-12 months after recovery from covid-19 fatigue. ceban f (24) canada 81 29, 128 * mesoscale-discovery (msd) multiplexed immunoassay (immunological parameters), self-report, tics-m (cognitive function), eq-5d-5l (quality of life), moca (cognitive function), sf-20 (quality of life) 3-6 months after testing positive for covid-19 median 85 days fatigue chen c, haupert sr (25) usa 50 1, 680, 003 * * 3-9 months after diagnosis fatigue and joint pain this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 16 table 2: characteristics of 50 included studied in the umbrella review fernándezde-laspeñas c (26) spain 29 24, 255 * * * * median 82 days palpitation, fatigue, depression, apnea, throat ache, joint pain lopezleon s (7) usa 15 47, 910 * * chest x-ray, chest ct, d-dimer, crp fatigue, depression, shortness of breath michelen m (27) uk 32 10, 951 * * self-report, physical assessment median 221 days fatigue, depression, shortness of breath, lung abnormalities nguyen nn (28) germany 37 n/a * * * self-report, physical assessment 35-90 days fatigue, depression, apnea, joint pain salamanna f (29) italy 145 22, 254 * * * abnormal lung functions up to 6 months, cardiovascular up to 8 months palpitation, cardiovascular injury, anxiety, depression, fatigue, body aches, olfactory dysfunction, sandra willi (62) switzerland 31 48, 246 * * * chest ct, radiological findings 11-90 days respiratory up to 12 weeks after hospital admission cardiovascular 11 weeks after onset of covid-19 symptoms impaired pulmonary function, breathlessness, decrease in quality of life, pulmonary fibrosis, myocarditis, fatigue yang t (30) germany 72 88, 769 * * * * average 95 days average after more than 9 months fatigue, depression, joint pain, arthralgia, dyspnea, alopecia, anxiety zeng n (31) china 151 1, 285, 407 * * chest ct, radiological findings mental sequela up to 12 months abnormal pulmonary function tests, fatigue, memory impairment, depression, ptsd almas t (32) ireland 21 54730 * * * chest pain after 60 days of illness, ongoing palpitations after 6-months 60 days – 6 months fatigue, dyspnea, arthralgia, alopecia, anxiety, hyperhidrosis, insomnia ahmad ms (33) saudi arabia 20 14146 * * * * standard questionnaires, pfts, qol assessment parameters, chest ct, mri, spirometry from 4 weeks – 6 months fatigue, dyspnea, cough, sore throat, joint pain, chest pain, loss of smell/taste, depression, headache, diarrhea, anxiety, loss of memory healey q (34) uk 19 10643 * * * * chest ct, biomarkers up to 4 weeks after acute infection fatigue, dyspnea, gustatory dysfunction, cough, olfactory dysfunction, myalgia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 17 archives of academic emergency medicine. 2023; 11(1): e28 table 2: characteristics of 50 included studied in the umbrella review d’ettorre g (35) italy 13 4395 * * * chest ct, mri, 6mwt, d-dimer, pfts from 9 – 291 days sleep difficulties, dyspnea, chest pain, loss of smell, ptsd, anxiety, depression, headache, pulmonary fibrosis, muscle weakness, brain fog, dizziness groff d (36) usa 57 250351 * * pfts , ct, mri, phq, mmrc, 6mwt, body plethysmography, echo, gad-7, sgrq, eq-5d-5l, hads, mmse, sf-12, scip, wais-iii, ptsd (dts), cfq-11 30 days after illness and beyond up to 6 months difficulty concentrating, generalized anxiety disorder, memory deficits, fatigue, cognitive impairment, anosmia, dysgeusia han q (37) uk 18 8591 * * * validated questionnaires, mmrc, hads, insomnia severity index up to 12 months from 3-12 months fatigue, dyspnea, depression, arthromyalgia, anxiety, insomnia, memory loss, concentration difficulties iwu cj (38) south africa 11 86 * * * ct, biomarkers, laboratory tests, pfts, validated survey instruments, vascular changes up to 6 weeks after infection 12th week after discharge fatigue, cough, sleep disorders, shortness of breath, depression, anxiety iqbal fm (39) uk 43 12974 * * * mri, sf-36, wemwbs, pet scan, ct scan, lmmrc scale, cfs, sf-36, ptsd, hads questionnaires up to 12 weeks and beyond fatigue, sleep disturbance, dyspnea, anxiety seyedalinaghi s (40) iran 65 n/a * * * * * * * mri up to 8-10 weeks and beyond lung, liver, kidney, and heart injuries, neurological injuries, cardiac/brain stroke, hypoproteinemia, encephalopathy, thromboembolism, septic shock, multiple organ dysfunction syndromes, psychological distress jennings g (41) ireland 39 8293 * * * spirometry, ct, hrct, cxr, mri, pfts, eq-5d-5l up to 31 weeks fatigue, sleep disorder, depression, cognitive impairments, confusion, cough, dyspnea, anxiety, arthralgia, myalgia, headache, chest pain, throat pain, fever, expectoration, weight loss, skin problems, anosmia, ageusia, hair loss ma y (42) china 40 10, 945 * * * ct, pfts, mmrc, gad-7 scores, 6mwt, eq-5d-5l up to 6 months and above at 12 months and beyond fatigue, mild dyspnea, anxiety, depression, sleep difficulty, difficulty concentrating, myalgia, joint pain, rhinorrhea malik p (43) usa 12 4828 * * * eq-5d-5l, vas scale fatigue, cough, chest pain, dyspnea, anosmia, arthralgia, headache, sleep disturbances, mental health problems, poor qol this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index sa. seyedalinaghi et al. 18 table 2: characteristics of 50 included studied in the umbrella review cabrera martimbianco al (44) brazil 25 5440 * * * from 3 to 24 weeks chest pain, arthralgia, dyspnea, cough, fatigue, sputum production, sleep disorders, cognitive and memory impairment, myalgia, functional impairment sanchezramirez dc (45) canada 24 5323 * * ct, pfts, mmrc, wpai, performance-based tests, sppb, 1-mstst, 2mwt, 6mwt, eq-5d-5l, sf-36 up to 6 months after infection fatigue, chest pain, cough, dyspnea, poor qol sandler cx (46) australia 21 7639 * blood count, cxr, ct, pfts, ecg, echo, validated multi-item fatigue questionnaire up to 16–20 weeks from 8 weeks and beyond fatigue abbreviations: chest x-ray (cxr), chronic fatigue syndrome (cfs), computed tomography (ct), george’s respiratory questionnaire (sgrq), high-resolution computed tomography (hrct), hospital anxiety and depression (hads), magnetic resonance imaging (mri), mini-mental state examination (mmse), modified medical research council (mmrc), positron emission tomography (pet), posttraumatic stress disorder (ptsd), pulmonary function tests (pfts), quality of life (qol), the 36-item short form survey (sf-36), the short physical performance battery (sppb), the warwick-edinburgh mental wellbeing scale (wemwbs), work productivity and activity impairment (wpai) supplementary 1: the study search strategy in different databases pubmed search query; time of search: 29 august 2022; results: 453 ("covid-19"[mesh] or "sars-cov-2"[mesh] or covid-19[tiab] or sars-cov-2[tiab] or coronavirus disease 2019[tiab] or severe acute respiratory syndrome coronavirus 2[tiab]) and (long-term outcome*[tiab] or long-term complication*[tiab] or late complication*[tiab] or chronic complication*[tiab] or long-term effect*[tiab] or long-term impact*[tiab] or consequence*[tiab] or sequelae[tiab] or long covid[tiab] or sequel[tiab] or post-acute covid syndrome[tiab] or long-covid[tiab] or post-acute covid19 syndrome[tiab]) and (systematic review[tiab] or meta-analysis[tiab]) embase search query; time of search: 29 august 2022; results: 496 (’coronavirus disease 2019’/exp or ’severe acute respiratory syndrome coronavirus 2’/exp or ’covid-19’:ab,ti or ’sars-cov-2’:ab,ti or ’coronavirus disease 2019’:ab,ti or ’severe acute respiratory syndrome coronavirus 2’:ab,ti) and (‘long covid’/exp or ‘long-term outcome*’:ab,ti or ‘long-term complication*’:ab,ti or ‘late complication*’:ab,ti or ‘chronic complication*’:ab,ti or ‘long-term effect*’:ab,ti or ‘long-term impact*’:ab,ti or ‘consequence*’:ab,ti or ‘sequelae’:ab,ti or ‘long covid’:ab,ti or ‘sequel’:ab,ti or ‘postacute covid syndrome’:ab,ti or ‘long-covid’:ab,ti or ‘post-acute covid19 syndrome’:ab,ti) and (‘systematic review’:ab,ti or ‘metaanalysis’:ab,ti) scopus search query; time of search: 29 august 2022; results: 495 (title-abs (“covid-19” or “sars-cov-2” or “coronavirus disease 2019” or “severe acute respiratory syndrome coronavirus 2”)) and (title-abs (“long-term outcome*” or “long-term complication*” or “late complication*” or “chronic complication*” or “longterm effect*” or “long-term impact*” or “consequence*” or “sequelae” or “long covid” or “sequel” or “post-acute covid syndrome” or “long-covid” or “post-acute covid19 syndrome”)) and (title-abs (“systematic review” or “meta-analysis”)) web of science search query; time of search: 29 august 2022; results: 452 (ts= (“covid-19” or “sars-cov-2” or “coronavirus disease 2019” or “severe acute respiratory syndrome coronavirus 2”)) and (ts= (“long-term outcome*” or “long-term complication*” or “late complication*” or “chronic complication*” or “long-term effect*” or “long-term impact*” or “consequence*” or “sequelae” or “long covid” or “sequel” or “post-acute covid syndrome” or “longcovid” or “post-acute covid19 syndrome”)) and (ts= (“systematic review” or “meta-analysis”)) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e22 or i g i n a l re s e a rc h short-term side effects of mrna-based covid-19 vaccine among jordanian population; a cross-sectional study razan i. nassar1∗ 1. department of clinical pharmacy and therapeutics, faculty of pharmacy, applied science private university, amman, jordan. received: october 2022; accepted: december 2022; published online: 12 february 2023 abstract: introduction: one type of the developed covid-19 vaccines that received emergency permission and was approved by the food and drug administration (fda) is the mrna-based vaccine. the aim of this study is to gather information on the jordanian population’s experience with the vaccine’s side effects. methods: the study objectives were addressed through a cross-sectional study, which collected information regarding the short-term side effects experienced by the vaccinated individuals within one month following the injection of an mrna-based covid-19 vaccine. data collection was carried out in august 2021. participants were invited to take part in a self-administered web-based survey created using google forms. results: among the study’s participants (n= 533), about 56% experienced side effects after the first dose of the mrna-based covid-19 vaccine. the most commonly reported side effects after the first dose were sore arm at the injection site (91.6%), and fatigue (83.06%). the female gender was significantly associated with experiencing fatigue, discomfort, chills, and hair loss. being over 30 years old was significantly associated with experiencing cough. being a smoker was significantly associated with experiencing shortness of breath and gastrointestinal symptoms. conclusion: the mrna-based covid-19 vaccine side effects were common, yet, mild, local, and self-limited. the local pain at the injection site was the most commonly reported side effect. hopefully, the study’s findings will aid in lowering resistance to vaccination. keywords: coronavirus; covid-19; adverse effects; vaccines; mrna vaccine; covid-19 vaccines; jordan cite this article as: i. nassar r. short-term side effects of mrna-based covid-19 vaccine among jordanian population; a cross-sectional study. arch acad emerg med. 2023; 11(1): e22. https://doi.org/10.22037/aaem.v11i1.1850. 1. introduction in december 2019, the novel coronavirus (sars-cov-2) was first recognized in wuhan, china. it causes a highly infectious disease referred to as covid-19 (1). the covid-19 has spread globally to turn into a worldwide pandemic (2). healthcare providers, policymakers, governments, and researchers were eagerly working around the clock to provide sufficient prevention and treatment modalities to fight the pandemic (3). worldwide, several preventive measures were imposed by the governments in order to reduce the spread of the virus and the burden on the healthcare sector; for example, quarantine and social distancing were imposed, also wearing a face mask was made mandatory in public places (4, 5). the public health emergency needed urgent efforts to develop and test the vaccines to combat the covid-19 pan∗corresponding author: razan i. nassar; applied science private university, amman 11931, jordan, p. o. box 166, email: r_nassar@asu.edu.jo, phone: w +9626 5609999, m +962 799770094, orcid: https://orcid.org/0000-0001-89520376. demic (3). thus, several vaccines were developed and granted emergency approval (6). one type of the developed vaccines is the mrna-based covid-19 vaccine, which was approved by the united states food and drug administration in december 2020 (7). to get fully vaccinated with the mrnabased vaccine, two doses are required; the second dose must be administered at least three weeks after the first dose. the vaccine can provide efficient protection one week after the second dose (8). in january 2021, jordan was one of the first countries to launch vaccination campaigns, giving emphasis to healthcare professionals and the elderly (9). despite the government’s continuous attempts to guarantee that most of the population is vaccinated; myths, fear, safety concerns, and negative beliefs have adversely shaped the perception of the public, which in turn affected the percentage of infected individuals. variation in public awareness and perception toward vaccines is generally documented (10-12). furthermore, hesitancy is another major factor that influenced the decision of the individual whether to receive the vaccine or not (11, 12). hesitancy associated with getting vaccinated is comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. i. nassar 2 mon, partly due to the fact that the covid-19 vaccines were rapidly developed (13). concerns and fears of individuals who are hesitant to vaccinate should be addressed. this calls for urgent public transparency and engagement (12). thus, it is crucial to collect data regarding covid-19 vaccines’ side effects in order to educate and clarify to the public what to anticipate post-vaccination. this information may contribute to increasing confidence in covid-19 vaccines, as well as, decreasing hesitancy. hence, the aim of this study is to gather information on the jordanian population’s experience with the covid-19 vaccine’s immediate side effects. 2. methods 2.1. study design and settings the study objectives were addressed through a crosssectional study, which was performed to collect information regarding the short-term side effects experienced by the vaccinated individuals within one month following the injection of an mrna-based covid-19 vaccine. data collection was carried out in august 2021. participants were invited to take part in a self-administered web-based survey created using google forms. the survey was adjusted in a way that allows the participant to send one response only. ethical approval for this study was obtained from the institutional review board committee at the faculty of pharmacy, applied science private university (ethics code: 2021-pha31). participation in the study was voluntary. informed consent to participate in the study was provided by participants. 2.2. participants eligibility criteria included residing in jordan, and having received at least one dose of the mrna-based covid-19 vaccine. individuals living in any geographic area were allowed to participate in the study. participants should have the ability to provide their information by completing the online survey. 2.3. data gathering the survey items were selected based on the existing information regarding the side effects of the mrna-based covid19 vaccine (pfizer-biontech®). following an extensive review of the literature on pubmed, google scholar, and other databases, the first draft of the survey was developed (8, 14, 15). the survey questions were reviewed to merge concepts and eliminate unrelated items. three experts in the field reviewed the first draft to ensure its face and content validity, then the survey was updated based on their feedback. assessment criteria were sent to them (appropriateness of the words used, clarity of items, suitability of content, consistency of survey style and its layout). they informed the research team that the survey is clear, comprehensive, the items are relevant to the study objectives and suitable for the study’s aim. moreover, they confirmed that the study survey is free from difficult terminology and medical jargon. to assess the clarity of words and item comprehension, a pilot study was conducted. the pilot study participants were excluded from the analysis of the current study, and additional amendments were conducted based on their suggestions. to finalize, the questions were re-evaluated to make them concise and suitable for online administration (format, sequencing, general clarity, and graphic layout). the final developed survey was organized into two major sections addressing the domains of interest. the first section included items to collect participants’ demographic data, such as gender, age, marital status, educational level, employment, living place, and nationality. additionally, the following information was also collected; whether they were smokers, had any chronic disease(s), whether they were using any medication(s), and if they were previously infected with covid-19. the second section included items that aimed to collect information regarding the side effects experienced following the injection of mrna-based covid-19 vaccine; the following data were collected: the date of vaccination (month), the number of doses that were taken (one or two doses), and the side effects that were experienced after receiving each dose. additionally, in this section, participants were asked if they needed hospitalization within a month of receiving the vaccine, and they were requested to select the dose that caused the most severe side effects. 2.4. survey implementation study participants were recruited through social media (mainly facebook and whatsapp). as the first step in participants’ selection, they were asked if they had received the first dose of the mrna-based covid-19 vaccine. this question should be answered with ‘yes’ in order to be able to open the survey. eligible participants who indicated a willingness to participate in this study were also able to open a link to see the study’s ethics committee approval letter, and afterward, they were able to complete the survey. communication between the researcher and the participants was established via e-mail when needed. the survey was designed to take less than five minutes to be completed. 2.5. statistical analyses the sample size was determined based on population and the number of vaccinated individuals in jordan. it was calculated to be a minimum of 384 participants, using a margin of error of 5%, a confidence level of 95%, and a response distribution of 50% (16). the survey responses were coded and entered into a custhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e22 table 1: demographic characteristics of the studied participants (n= 533) parameter number (%) gender male 119 (22.3) female 414 (77.7) age (year) < 18 8 (1.5) 18-29 219 (41.1) 30-39 195 (36.6) 40-49 75 (14.1) 50-59 27 (5.1) ≥ 60 9 (1.7) marital status married 294 (55.0) single 217 (40.7) divorced 20 (3.8) widowed 2 (0.4) living place amman (the capital) 403 (75.6) other cities 130 (24.4) nationality jordanian 491 (92.1) non-jordanian 42 (7.9) educational level primary school 6 (1.1) some high school 27 (5.1) high school diploma 35 (6.6) bachelor’s degree 367 (68.9) postgraduate degree (master’s or phd) 98 (18.4) employment employed 282 (52.9) not employed 236 (44.3) retired 15 (2.8) smoker yes 154 (28.9) no 365 (68.5) previous smoker 14 (2.6) tomized database using the statistical package for the social sciences (spss), version 24.0 (ibm corp., armonk, new york, usa). qualitative variables were presented as percentages. fisher’s exact test was used to assess the association between each side effect after the first dose of the mrna-based covid-19 vaccine and participants’ gender, age, and smoking status. the p-value cutoff for significance was established at 0.05. 3. results 3.1. baseline characteristics of studied cases the survey was distributed to 545 participants; however, 12 individuals refused to participate in the current study leaving a response rate of 97.8%. the detailed demographic characteristics of the participants are listed in table 1. the majority of the study’s participants were female (77.7%), about 43% of the participants were less than 30 years old, more than half of the participants (55.0%) were married, 92.1% had a jordanian nationality, and 87.3% had a bachelor’s or postgraduate degree. more than half of the participants were employed (52.9%), and about one-third of the participant were smokers (28.9%). the most common comorbidity among the participants was allergy (19.5%). the percentages of other comorbidities were low, ranging from 0.4% (chronic obstructive pulmonary disease) to 6.6% (thyroid diseases). more than half of the participants (52.7%) were not infected prior to receiving the mrna-based covid-19 vaccine, whereas, 37.9% had been affected with covid-19 prior to vaccination, and the remaining (9.4%) were unsure. in may 2021, 26.1% of the study’s participants had received the first dose of the mrna-based covid-19 vaccine, while the lowest percentage was reported in january 2021 (2.1%). 3.2. side effects regarding the side effects after the first dose of the mrnabased covid-19 vaccine, 300 (56.3%) cases reported experiencing various side effects. the most common side effect that was reported by the participants was sore arm at the site of injection (91.6%). fatigue and tiredness (83.6%), discomfort (69.6%), muscle/joint pain (60.3%), drowsiness (59.0%), and headache (57.6%) were reported by more than half of the participants (figure 1). association between side effects after the first dose of the mrna-based covid-19 vaccine and participants’ gender, age, and smoking status were investigated. as shown in figure 2, there is a significant association between the female gender and experiencing fatigue (p = 0.033), discomfort (p = 0.013), chills (p = 0.003), and hair loss (p-value= 0.017). a significant association was found between being older than 30 and experiencing cough (p = 0.046). furthermore, a significant association was found between being a smoker and experiencing shortness of breath (p = 0.042), and gastrointestinal symptoms (p = 0.049). out of the 533 participants, 402 (75.4%) had received the second dose of the mrna-based covid-19 vaccine. among those participants (n= 402), about 66.0% (n= 267) experienced side effects after the second dose of the mrna-based covid-19 vaccine. the most common side effect that was reported by the participants after the second dose was a sore arm at the site of injection (88.8%). fatigue, discomfort, muscle/joint pain, headache, and drowsiness were also reported by more than half of the participants (figure 1). more than half (58.8%) of the study participants who had side effects after both doses stated that the second dose was accompanied by more severe side effects; in contrast, 24.7% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. i. nassar 4 figure 1: side effects reported by the study’s participants after receiving the first dose (n= 300) and the second dose (n= 267) of the mrnabased covid-19 vaccine (the difference was only significant for drowsiness (p = 0.033)). chose the first dose, and 16.5% said there was no difference between the two doses. a statistically significant increase (p < 0.000) was found in the proportion of the participants who experienced side effects after the second dose (66.4%) compared to the first dose. moreover, as shown in figure 1, drowsiness was the only side effect that showed a significant difference in the proportion of participants who experienced it following the first and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e22 figure 2: association between experiencing side effects and gender, age, and smoking status among the study’s participants. the second dose of the mrna-based covid-19 vaccine (p = 0.033). 4. discussion this is the first cross-sectional study conducted on the jordanian population to specifically assess the side effects of mrna-based covid-19 vaccine. receiving the covid-19 vaccine is a major intervention toward containing the pandemic. however, it has been faced with hesitancy (17-19). limited data about the covid-19 vaccines development account for the high level of uncertainty and hesitancy toward covid-19 vaccine acceptance (17). hesitancy toward receiving the covid-19 vaccine should be addressed. thus, similar to the current study, several studies were conducted to reveal side effects associated with covid-19 vaccines in order to provide the general public with data regarding covid19 vaccines, which in turn would decrease hesitancy and explain to the public what to expect after the vaccination (8, 13, 15, 20-26). global vaccination campaigns have been launched to stop the covid-19 pandemic. real-world observing of covid-19 vaccine safety is still crucial even though clinical trial studies revealed that the majority of covid-19 vaccines have excellent safety and efficacy profiles. in the current study, sore arm at the injection site, fatigue, discomfort, muscle/joint pain, drowsiness, and headache were reported by more than half of the participants who experienced side effects (300 out of 533 participants for the first dose, and 267 out of 402 participants for the second dose) after both doses. these findings are in line with several published studies, and are consistent with the side effects listed by the united states centers for disease control and prevention (cdc) (27). for example, in saudi arabia, a survey-based study was conducted to assess the side effects of mrna-based covid-19 vaccine, 386 participants completed the survey. the most commonly reported side effects were local pain, fatigue, and muscle pain (79.3%, 42.0%, 39.1%, respectively) (28). another crosssectional study conducted in saudi arabia documented that the most common side effects reported by the participants were injection site pain, and headache (8). moreover, a crosssectional study was conducted among healthcare workers in czech republic (15). injection site pain (89.8%), fatigue (62.2%), headache (45.6%), muscle pain (37.1%), and chills (33.9%) were the most frequently reported side effects experienced by the study participants (n= 877). moreover, the side effects were more common among older participants (≤/≥43-year-old group) (15). another cross-sectional study was conducted among healthcare workers (n= 803 received the mrna-based covid-19 vaccine), and the most common side effects reported by more than half of the participants this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. i. nassar 6 were localized, generalized, and musculoskeletal symptoms (89.5%, 76.0%, 53.3%, respectively) (29). the reported rates of side effects have varied between conducted studies due to differences in race, age, and underlying conditions. a recent systemic review was undertaken to assess the mrna-based covid-19 vaccine side effects. the most frequently reported side effects among the total number of the participants (n= 10,632) in all articles (107 were screened, and 14 were included) were injection site pain, fatigue, muscle pain, local swelling, and headache (77.3%, 43.0%, 39.7%, 33.6%, 33.3%, respectively) (30). the review findings were in line with the current study findings, as the most commonly reported side effect among the current study’s population was sore arm at the injection site. it is obvious that injection site pain was the most commonly reported side effect among most of the studies conducted on different populations (31-33). moreover, local pain continues to be the most frequent side effect observed in multiple vaccine trials conducted in the past (34). the reason behind this finding may be explained by the fact that several factors contribute to the pain at the injection site such as the technique used for injection, injection velocity, and vaccine temperature. these factors are challenging to standardize and will have a significant impact on a person’s experience (35). it is advised to lower the arm that will be receiving the injection in order to reduce the pain, as an injection into a relaxed muscle causes less pain. furthermore, it is recommended that the medical staff participating in the vaccination process acquire proper training on the best injection technique to lessen differences in the way individuals experience pain after vaccination (36). males and females react to vaccination differently. as documented in a systemic review, the rate of experienced side effects is usually higher in females compared to males (69.8%, 30.2%, respectively) (30). being female, was a statistically significant factor for experiencing higher number of side effects in two cross-sectional studies conducted in saudi arabia (8, 28). various other published studies observed a gender difference, with females experiencing significantly more side effects compared to males (37, 38). this is consistent with the current study’s findings. moreover, the current study revealed that the female gender is significantly associated with experiencing fatigue, discomfort, chills, and hair loss. this is probably due to a combination of biological factors, such as hormones and genes. additionally, sex variation in pharmacodynamics and pharmacokinetics have been examined, with females being more susceptible to side effects (39). a medical officer at the cdc’s immunization safety office stated that women have more reactions to a range of vaccines. this covers both adult influenza and some childhood vaccinations, such as the hepatitis b, and measles, mumps, and rubella (mmr) vaccines (40). on the other hand, these findings should not be deemed bad news for women, as firstly, the side effects were mild, and self-limited, and secondly, interestingly, these physical responses indicate that the vaccine is effective and working. according to the results of the current study, experiencing cough was significantly associated with being older than 30. several studies assessed the relationship between age and side effects. baden et al. found that younger participants (18-64 years old) experienced side effects more frequently than participants over the age of 65 (41). another surveybased study conducted among german healthcare workers revealed that younger participants were more affected by the systemic side effects compared to the older age participants following receiving the mrna-based covid-19 vaccine (67.4% vs. 54.5%) (26). the authors’ decision to use a different age cutoff in each study may account for the variance in the studies’ findings. more than half of the current study’s participants stated that the second dose was accompanied by more severe side effects. two cross-sectional studies conducted in saudi arabia documented similar results, the first one recorded that after the second dose, higher numbers of side effects were reported by the participants compared to the first dose (28), and the second one indicated a significant increase in the proportion of respondents who experienced side effects after receiving the second dose compared to the first dose (8). according to the data collected by the cdc from mrna-based covid-19 vaccine recipients in the united states, more side effects were recorded after the second dose. furthermore, equivalent findings were generated by the fda (42), and several other studies (37). 5. limitations this study comes with some limitations. the study was based on an online survey, and this might be a source of selection bias. however, web-based recruitment of participants was found to be cost-effective, facilitating the reach of people who are otherwise difficult to reach, and representative (43, 44). in jordan, around 90% of the population have internet access, which makes them easy to reach using online-based questionnaires. another limitation of this study is that it was conducted while the vaccination campaign was still ongoing in jordan; therefore, the delayed side effects may not have been reported. 6. conclusions the current study reveals the side effects associated with the mrna-based covid-19 vaccine, which were common, yet, mild, local, and self-limited. the local pain at the injection site was the most commonly reported side effect. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e22 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest the author declares no relevant conflicts of interest or financial relationships. 7.3. fundings and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution r.n: conceptualization, methodology, validation, formal analysis, investigation, data curation, writing original draft preparation, writingreview and editing. references 1. sharma o, sultan aa, ding h, triggle cr. a review of the progress and challenges of developing a vaccine for covid-19. frontiers in immunology. 2020;11:585354. 2. covid live coronavirus statistics worldometer. 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the new york times. women report worse side effects after a covid vaccine 2021 [available from: https://www.nytimes.com/2021/03/08/health/vaccineside-effects-women-men.html. 41. baden lr, el sahly hm, essink b, kotloff k, frey s, novak r, et al. efficacy and safety of the mrna-1273 sars-cov-2 vaccine. new england journal of medicine. 2021;384(5):403-16. 42. u.s. food and drug administration. fda review of efficacy and safety of pfizer-biontech covid-19 vaccine emergency use authorization request 2020 [available from: https://www.fda.gov/media/144337/download. 43. fenner y, garland sm, moore ee, jayasinghe y, fletcher a, tabrizi sn, et al. web-based recruiting for health research using a social networking site: an exploratory study. journal of medical internet research. 2012;14(1):e1978. 44. cantrell ma, lupinacci p. methodological issues in online data collection. journal of advanced nursing. 2007;60(5):544-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references emergency. 2017; 5 (1): e50 le t t e r to ed i to r the australasian triage scale level 5 criteria may need to be revised; a commentary amir mirhaghi1∗, mohsen ebrahimi2 1. evidence-based caring research center, department of medical-surgical nursing, school of nursing and midwifery, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, imam reza hospital, mashhad university of medical sciences, mashhad, iran. received: march 2016; accepted: august 2016; published online: 14 january 2017 cite this article as: mirhaghi a, ebrahimi m.the australasian triage scale level 5 criteria may need to be revised; a commentary. emergency. 2017; 5(1): e50. dear editor australasian triage scale (ats) is used to prioritize incoming patients in the emergency department (ed) according to patient acuity. it’s a five-level triage scale endorsed by the australasian college for emergency medicine (acem). the ats categories are defined by physiological predictors (airway, breathing, circulation, and disability) and maximum waiting time to treatment (1: immediate, 2: 10 minutes, 3: 30 minutes, 4: 60 minutes and 5: 120 minutes) (1). triage scales should be valid and reliable to ensure safe practice and promote clinical applicability in ed (2). ebrahimi et al. reported that the pooled coefficient for ats is fair: 0.390 (95% ci 0.307–0.466) (3). i’d like to bring your attention to the fact that ats has used the same criteria for level 4 and 5. patients with normal glasgow coma scale (gcs), patent airway and no respiratory distress and haemodynamic compromise may be allocated either to level 4 or 5 (1). therefore, it has to be said that a source of confusion may exist in ats level 4 and 5. studies have also reported that ats level 5 patients have not been recognized accurately and consistently by triage nurses (3, 4), despite the fact that ats level 5 patient presentations are less urgent and usually easily distinguishable. however, these kinds of patients are not critically ill, their number is usually higher than patients of other categories and they may also be over triaged into upper categories by triage nurses and so urgent patients may encounter significant delay and harm. the reason may lay in adult physiological predictors (app) in ats that do not significantly differentiate between category 4 and 5 criteria (1). it’s also worth mentioning that contrary to emergency severity scale (esi), ats does not have ∗corresponding author: amir mirhaghi; evidence-based caring research center, department of medical-surgical nursing, school of nursing and midwifery, mashhad, iran. email: mirhaghia@mums.ac.ir . a tendency to allocate patients into a specific category (5). a recent study on validity and reliability of ats has reported an overall inter-rater agreement of 0.40 using fleiss’ kappa coefficient, representing a fair-to-good level of inter-rater agreement, as well as the fact that the lowest coefficient of reliability belongs to level 5 (0.47) (4). although, 65% of the participant responses to all triage scenarios were accurate, only 40% of triage decisions in level 5 has been accurate, representing the least value among triage categories (4). therefore, fair consistency and low accuracy in category 5 raises serious questions that category 5 criteria may lack sufficient clarity, precision or accuracy. finally, since ats needs to be modified periodically, like any other triage scale (6), it’s recommended that level 5 criteria should be revised to ensure safe practice in ed. references 1. aging doha. emergency triage education kit: workbook 2009. available from: http://www.health.gov.au/internet/main/publishing.nsf/ content/casemix-ed-triage+review+fact+sheet+docum ents. 2. esmailian m, zamani m, azadi f, ghasemi f. interrater agreement of emergency nurses and physicians in emergency severity index (esi) triage. emergency. 2014;2(4):158. 3. ebrahimi m, heydari a, mazlom r, mirhaghi a. the reliability of the australasian triage scale: a meta-analysis. world j emerg med. 2015;6(2):94-9. 4. ekins k, morphet j. the accuracy and consistency of rural, remote and outpost triage nurse decision making in one western australia country health service region. australasian emergency nursing journal. 2015;18(4):227-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. mirhaghi and m. ebrahimi. 2 5. mirhaghi a, kooshiar h, esmaeili h, ebrahimi m. outcomes for emergency severity index triage implementation in the emergency department. journal of clinical and diagnostic research: jcdr. 2015;9(4):oc04. 6. considine j, shaban rz, fitzgerald gj, thomas s, graham ca. triage and ats: collateral damage in the quest to improve ed performance. australasian emergency nursing journal. 2012;15(4):185-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references archives of academic emergency medicine. 2023; 11(1): e42 or i g i n a l re s e a rc h the value of complete blood count parameters in predicting complicated acute appendicitis; a prognostic accuracy study natchanok mekrugsakit1, thawatchai tullavardhana1∗ 1. department of surgery, faculty of medicine, srinakharinwirot university, ongkharak nakhon-nayok, thailand. received: march 2023; accepted: april 2023; published online: 3 june 2023 abstract: introduction: low accuracy of clinical variables can result in delayed diagnosis and increase the incidence of complicated appendicitis in some cases. this study aimed to determine the value of simple complete blood count (cbc) biomarkers in predicting complicated appendicitis. methods: this is a single-center retrospective cross-sectional study, which was conducted on cases referred to emergency department following acute appendicitis who underwent appendectomy, to evaluate the accuracy of some cell blood count variables (white blood cell count (wbc), neutrophil percent, neutrophil to lymphocyte ratio (nlr), platelet to lymphocyte ratio (plr), mean platelet volume (mpv )) in predicting complicated cases (gangrenous and ruptured appendicitis). results: there were 252 (68.3%) patients in the uncomplicated appendicitis group and 117 (31.7%) patients in the complicated appendicitis group. the mean age of patients was 34.1 ± 1.09 (range: 18 -79) years (55.3% male). there were no differences between groups regarding the mean age (p = 0.053), gender distribution (p=0.07), alvarado score (p = 0.055), platelet count (p =0.204), plr (p = 0.115), and mpv (p = 0.205). the complicated appendicitis cases had longer onset of symptoms (p <0.001), higher wbc count (p = 0.011), higher neutrophil count (p < 0.001), and higher nlr (p < 0.001). neutrophil count (area under the curve (auc) = 0.61, 95% confidence interval (ci) = 0.56-0.66; p = 0.001) and nlr (auc = 0.65, 95% ci = 0.60-0.69; p = 0.001) had higher level of accuracy in this regard. in contrast, the area under the curve of wbc count (auc = 0.57, 95% ci = 0.52-0.63; p = 0.22), platelet count (auc = 0.44, 95% ci = 0.38-0.49; p = 0.049), plr (auc = 0.57, 95% ci = 0.52-0.62; p = 0.026), and mpv (auc = 0.54, 95% ci = 0.49-0.60; p = 0.193) showed low accuracy in predicting complicated acute appendicitis. conclusion: based on the findings of present study it seems that wbc, neutrophil percent, nlr, plr, and mpv have failed to poor accuracy in predicting cases with complicated appendicitis in emergency department. keywords: appendicitis; biomarkers; leukocyte count; emergencies cite this article as: mekrugsakit n, tullavardhana t. the value of complete blood count parameters in predicting complicated acute appendicitis; a prognostic accuracy study. arch acad emerg med. 2023; 11(1): e42. https://doi.org/10.22037/aaem.v11i1.2020. 1. introduction acute appendicitis is the most common emergency surgical condition, with a 229 per 10,000-person incidence and a lifetime risk of 6.7% to 8.6%. peak incidence is usually between the ages of 15 and 20 (1, 2). the clinical diagnosis of acute appendicitis has a sensitivity of 54%, specificity of 75%, positive and negative predictive values of 92.3% and 83.3%, respectively, and an accuracy of 89.8%, according to the alvarado score (3). however, the diagnostic accuracy is relatively low in women of reproductive age, which can result in diagnostic ∗corresponding author: thawatchai tullavardhana; department of surgery, faculty of medicine, srinakharinwirot university, ongkharak, nakhonnayok, thailand. 26120, phone number: 66-37395085-11201, 66-879791989, e-mail:thawatchait@g.swu.ac.th, orcid: https://orcid.org/0000-0002-4607983x. delays (4, 5). delayed or missed diagnosis of acute appendicitis can occur in 15-24% of cases, leading to complicated appendicitis (such as gangrenous, ruptured appendicitis and appendiceal abscess) and an increase in postoperative morbidity and mortality (6, 7). currently, computed tomography (ct) scans play an important role in the diagnosis of acute appendicitis, with sensitivity and specificity of 96.7% and 95.5%, respectively (8). however, ct scans may not be available in rural hospitals in developing countries. white blood cell count (wbc), neutrophil percent, neutrophil to lymphocyte ratio (nlr), platelet to lymphocyte ratio (plr), and mean platelet volume (mpv ) are all cbc biomarkers that are important in the response to acute inflammation and useful in the diagnosis of acute appendicitis. nevertheless, the value of those biomarkers in predictthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. mekrugsakit & t. tullavardhana 2 ing complicated appendicitis is uncertain, as the sensitivity and specificity of wbc were reported as 53% and 67%, respectively and the sensitivity and specificity of nlr were reported as 70.7% and 56.3% (9, 10). the goal of this study was to assess the value of simple cbc biomarkers such as wbc, neutrophils, nlr, plr, and mpv in predicting complicated appendicitis. 2. methods 2.1. study design and setting this is a single-center retrospective cross-sectional study, which was conducted on cases referred to emergency department following acute appendicitis who underwent appendectomy to evaluate the accuracy of some blood cell count variables (wbc, neutrophil percent, nlr, plr, mpv ) in predicting the complicated cases with peritonitis. the study was done in emergency surgical unit, department of surgery, faculty of medicine, srinakarinwirot university, ongkharak nakhon-nayok, thailand, between january 1, 2016 and march 31, 2022. the method of research was approved by the institutional ethics committee of srinakharinwirot university (ethics code: swuec/e-253/2564). patient information was gathered in accordance with the standards for the protection of personally identifiable health information. 2.2. participants the study included participants aged 18 to 70 who had acute appendicitis and were treated at our institute with an appendectomy (both open and laparoscopic surgery). those with advanced age, pregnancy, atherosclerotic disease, diabetes mellitus, hematologic disease, or use of steroids or immune-suppressants, which can affect serum biomarker interpretation, were excluded. patients who had previous laparotomies were not excluded from the study. 2.3. data gathering from april 1 to november 1, 2022, the patient’s data were obtained from an institutional computerized database program using the keywords acute appendicitis, appendicitis with peritonitis, and appendectomy for potential recruitment. acute appendicitis was confirmed by clinical, laboratory, and imaging tests, such as ultrasonography and computed tomography. prior to administering antibiotics, a blood sample was drawn at the time of admission to evaluate the patient’s wbc, neutrophils, lymphocytes, platelet count, and mpv. laboratory data was used to calculate the nlr and plr. the patients were operated on by our department’s surgical staff, and 98.7% of the patients were approached using the open appendectomy technique. both authors extracted patient information from the electronic database of the institution. for each patient, demographic data, intraoperative findings, and treatment outcomes (including postoperative complications and length of stay) were collected. patients were divided into two groups based on pathologic and intraoperative findings: uncomplicated acute appendicitis (acute focal and suppurative appendicitis) and complicated acute appendicitis (gangrenous and ruptured appendicitis). the postoperative outcomes were assessed during a 14–30-day follow-up period. 2.4. statistical analysis spss 22.0 (spss inc., chicago, il, usa) was used for statistical analysis. clinical and demographic factors were assessed using descriptive analysis (percentage, mean, standard deviation, minimum-maximum), and compared between groups using student t-tests for continuous variables, and mann whitney-u tests for non-normal parameters. p-value less than 0.05 was considered statistically significant. the receiver operating characteristic (roc) curve was used to determine the diagnostic value of studied serum biomarkers for complicated appendicitis considering the operative findings as gold standard. the best cut-off point for each biomarker was calculated using the area under the roc curve (auc) and specificity, sensitivity, positive and negative predictive values; in addition, positive and negative likelihood ratio of studied markers were calculated and reported with 95% confidence interval (ci). the area under the roc curves were classified as excellent (0.90-1), good (0.80-0.89), fair (0.70-0.79), poor (0.60-0.69) or fail (0.50-0.59). 3. results 3.1. baseline characteristics of studied cases appendectomy procedures were performed on 390 patients, but only 369 consecutive patients were recruited for the study. twenty-one cases were excluded since they met the exclusion criteria or lacked sufficient data. there were 252 (68.3%) patients in the uncomplicated appendicitis group and 117 (31.7%) patients in the complicated appendicitis group. the mean age of patients was 34.1 ± 1.09 (range: 18 -79) years (55.3% male). almost all of the procedures were performed via the open approach. table 1 compares the baseline characteristics of the patients between studied groups. there were no differences between the groups regarding mean age (p = 0.053), gender distribution (p=0.07), alvarado score (p = 0.055), platelet count (p =0.204), plr (p = 0.115), and mpv (p = 0.205). the complicated appendicitis cases had longer onset of symptoms (p <0.001), higher wbc count (p = 0.011), higher neutrophil count (p < 0.001), and higher nlr (p < 0.001). the length of stay for patients with complicated appendicithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e42 tis was significantly longer (4.67± 0.22 days versus 2.29± 0.70 days; p < 0.001). there was no statistically significant difference between groups in operative time (p = 0.069) or postoperative complication rate (p = 0.523). 3.2. screening performance characteristics of studied parameters the area under the roc curve of studied parameters in predicting the cases with complicated appendicitis are shown in table 2 and figure 1. neutrophil count (auc = 0.61, 95% ci = 0.56-0.66; p = 0.001) and nlr (auc = 0.65, 95% ci = 0.600.69; p = 0.001) had higher level of accuracy in this regard. in contrast, the area under the curve of wbc count (auc = 0.57, 95% ci = 0.52-0.63; p = 0.22), platelet count (auc = 0.44, 95% ci = 0.38-0.49; p = 0.049), plr (auc = 0.57, 95% ci = 0.520.62; p = 0.026), and mpv (auc = 0.54, 95% ci = 0.49-0.60; p = 0.193) showed low accuracy in predicting the complicated acute appendicitis. the sensitivity and specificity of neutrophil count in predicting complicated appendicitis in cut-off point of 83% were 64.02% (95% ci = 0.52-0.70) and 52.37% (95% ci = 0.48-0.61), respectively. these measures for nlr in cut-off point of 7.4 were 62.54% (95% ci = 0.52-0.70) and 58.92% (95% ci = 0.540.66), respectively. 4. discussion appendectomy is currently the gold standard in the treatment of acute appendicitis, with a 0.09-0.24 percent mortality rate. a delayed diagnosis may result in complicated appendicitis, requiring more complex surgery and increasing morbidity by 35%. (e.g., wound infection and intraabdominal abscess) (11, 12). even in this study, there was no difference in the rate of postoperative complications between the two groups; however, complicated appendicitis required a longer hospital stay. according to the results of a study, delayed presentation is a strong risk factor for developing complicated appendicitis; other risk factors included pediatric patients, those over the age of 70, male sex, and more than three comorbidities (13). thereby, basic biomarkers in the cbc that can be collected in the emergency department become a potential predictor of complicated appendicitis, encouraging the decision to perform emergency surgery in this group of patients. the primary goal of this study was to determine the value of cbc biomarkers in predicting complicated appendicitis. however, the results of this study indicate that complete blood counts parameters, including wbc, neutrophil count, nlr, platelet counts, plr, and mpv, failed to accurately predict cases of complicated appendicitis in the emergency department. previous studies demonstrated that wbc > 15,000/mm3 can predict acute appendicitis, whereas wbc > 18,000/mm3 can predict complicated appendicitis (14, 15). however, the results of this study indicate that a neutrophil with a cut-off value of 83% was unable to predict complicated appendicitis with adequate sensitivity and specificity. similarly, the results demonstrated that wbc was incapable of predicting complicated appendicitis. wbc has a sensitivity of 67% and a specificity of 43% in the diagnosis of complicated appendicitis, according to a study by sevinç et al. (16). nlr and plr are biomarkers associated with systemic inflammation. several studies have demonstrated that nlr has diagnostic value for acute appendicitis (17). in addition, hajibandeh et al. discovered that nlr > 4.7 and > 8.8 were independent predictors of simple and complicated appendicitis, respectively (18). in contrast to the study’s findings, nlr at a cut-off level of 7.4 has a low predictive potential for complicated appendicitis, with a sensitivity and specificity of 62% and 58%, respectively. previous studies demonstrated that plr at a cut-point value of 284 (auc: 0.647; sensitivity: 42%; specificity: 86%) has predictive capabilities in pediatric patients for the diagnosis of complex appendicitis (19). according to the findings of the present study, plr did not demonstrate value as a diagnostic biomarker for complicated appendicitis in adult populations. a recent meta-analysis found that a lower mvp value could be used to predict acute appendicitis but failed to demonstrate the diagnostic value of mpv for complicated appendicitis (20). consistent with the findings of the study, this can be explained by increase in mpv during the period of severe infection or sepsis as a result of platelet activation, due to an increase in the production of young platelets, which could affect mpv interpretation (21). given that there is currently no clinical scoring system to predict complicated appendicitis, future research may use the findings of this study to develop a clinical score that uses serum biomarkers as parameters to encourage early surgical management of complicated appendicitis patients, potentially improving their postoperative outcomes. 5. limitations the current study has two limitations: 1) it was retrospective, and 2) pregnant women and patients over 70 were excluded since they may present with unusual symptoms, delaying appendicitis diagnosis. however, this study’s large patient population provides accurate data for analysis. furthermore, if blood test was delayed, the progression of the disease could have exacerbated the inflammatory response, affecting the interpretation of serum biomarkers. this may lead to data bias or imprecision. in this study, if the patient was suspected to have acute appendicitis, a blood samthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. mekrugsakit & t. tullavardhana 4 figure 1: receiver operating characteristics (roc) curves of the studied biomarkers in predicting complicated appendicitis cases. table 1: comparing the baseline characteristics as well as outcomes of studied patients between cases with complicated and uncomplicated appendicitis parameters appendicitis group p-value complicated uncomplicated age (year) mean ± sd 38.3±1.27 35.22±1.17 0.053 gender male/female ratio 128/124 77/40 0.07 alvarado score mean ± sd 7.67 ± 1.44 7.14 ± 2.11 0.055 onset of symptom (hour) mean ± sd 30.13 ± 2.15 15.15 ± 1.22 < 0.001 wbc (cell/mm3 ) mean ± sd 16507 ± 403 15394 ± 389 0.011 wbc differential pmn (%) 85.00 ± 0.45 81.10 ± 0.66 < 0.001 platelet count (cell/mm3 ) 264333±6064.2 280581±6020 0.204 nlr 13.3±1.27 8.2±0.51 < 0.001 plr 267.9 ± 35.0 204.8 ± 22.2 0.115 mpv 9.98 ± 0.08 9.80 ± 0.07 0.205 treatment outcomes operative times (minutes) 67.38 ± 2.70 61.25 ± 2.60 0.069 length of stay (days) 4.67± 0.22 2.29 ± 0.70 <0.001 overall post-operative complications 4 (1.60) 3 (2.610) 0.523 data are presented as mean ± standard deviation (sd) or frequency (%). wbc = white blood cell count; pmns = polymorph nuclear neutrophils; nlr = neutrophil to lymphocyte ratio; plr = platelet to lymphocyte ratio; mpv = mean platelet volume. ple was drawn immediately and results were provided within 30–45 minutes. the patient’s biomarker-affecting comorbidities were eradicated, and surgical care was administered within 24 hours of diagnosis, this could mimic the risk of bias in this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e42 table 2: screening performance characteristics of studied markers in predicting the complicated cases of acute appendicitis variable cut-off sensitivity specificity ppv npv +lr -lr accuracy wbc 15150 62 (0.53-0.71) 50 (0.43-0.55) 36.13 (0.30-0.43) 73.66 (0.660.80) 1.22 (1.01-1.47) 0.77 (0.59-1.00) 53.12 (0.45-0.58) neutrophil 83 64 (0.52-0.70) 52 (0.48-0.61) 38.89 (0.31-0.46) 75.03 (0.68-0.81) 1.34 (1.10-1.63) 0.72 (0.56-0.92) 56.47 (0.51-0.62) platelet 242500 61 (0.52-0.70) 50 (0.45-0.57) 28.12 (0.23-0.34) 60.19 (0.51-0.69) 0.84 (0.72-0.99) 1.43 (1.05-1.94) 37.94 (0.33-0.43) nlr 7.4 62 (0.53-0.70) 58 (0.54-0.66) 41.61 (0.34-0.49) 77.05 (0.70-0.83) 1.54 (1.25-1.89) 0.64 (0.50-0.82) 60.43 (0.55-0.65) plr 144.4 55 (0.46-0.64) 44 (0.37-0.50) 34.58 (0.28-0.41) 72.41 (0.65-0.73) 1.14 (0.96-1.35) 0.82 (0.62-1.08) 50.15 (0.45-0.55) mpv 10 61 (0.55-0.66) 47 (0.37-0.56) 35.25 (0.28-0.43) 70.90 (0.64-0.70) 1.17 (0.92-1.50) 0.83 (0.73-1.08) 55.83 (0.51-0.61) data are presented with 95% confidence interval. wbc = white blood cell count; nlr = neutrophil to lymphocyte ratio; plr = platelet to lymphocyte ratio; mpv = mean platelet volume; ppv: positive predictive value; npv: negative predictive value; +lr: positive likelihood ratio; -lr: negative likelihood ratio. 6. conclusion based on the findings of present study it seems that cell blood count parameters such as wbc, neutrophil percent, nlr, plr, and mpv have failed to poor accuracy in predicting the cases with complicated appendicitis in emergency department. 7. declarations 7.1. acknowledgments the authors thank the surgical staff at department of surgery, faculty of medicine, srinakahrinwirot university for the acquisition of data. 7.2. conflict of interest the authors declare no conflict of interest in this study. 7.3. fundings none. 7.4. authors’ contribution dr. thawatchai tullavardhana worked on study conception and design, acquisition, analysis, interpretation of data, editing. dr. natchanok mekrugsakit worked on study design, data collection, data analysis, the preparation of a manuscript. all authors read and approved the final version of manuscript. 7.5. data availability the standards for the protection of personally identifiable health information were used to safeguard patient information. 7.6. disclosure the findings of this study are presented at annual scientific congress of the international college of surgeons, thailand. 21-22 november 2022. 7.7. using artificial intelligence chatbots this study made no use of artificial intelligence chatbots. references 1. wickramasinghe dp, xavier c, samarasekera dn. the worldwide epidemiology of acute appendicitis: an analysis of the global 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p, rinta-kiikka i, paajanen h, rautio t, nordström p, et al. the accuracy of the computed tomography diagnosis of acute appendicitis: does the experience of the radiologist matter? scand j surg. 2018;107(1):43-7. 9. acharya a, markar sr, ni m, hanna gb. biomarkers of acute appendicitis: systematic review and cost-benefit trade-off analysis. surg endosc. 2017;31(3):1022-31. 10. aydin ou, soylu l, dandin o, uysal aydin e, karademir s. laboratory in complicated appendicitis prediction and predictive value of monitoring. bratisl lek listy. 2016;117(12):697-701. 11. liao yt, huang j, wu ct, chen pc, hsieh tt, lai f, et this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. mekrugsakit & t. tullavardhana 6 al. the necessity of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy: a retrospective 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et al. diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. ulus travma acil cerrahi derg. 2016;22(2):155-62. 17. shimizu t, ishizuka m, kubota k. a lower neutrophil to lymphocyte ratio is closely associated with catarrhal appendicitis versus severe appendicitis. surg today. 2016;46(1):84-9. 18. hajibandeh s, hobbs n, mansour m. neutrophil-tolymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: a systematic review and meta-analysis. am j surg. 2020;219(1):154-63. 19. celik b, nalcacioglu h, ozcatal m, altuner torun y. role of neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. ulus travma acil cerrahi derg. 2019;25(3):222-8. 20. tullavardhana t, sanguanlosit s, chartkitchareon a. role of platelet indices as a biomarker for the diagnosis of acute appendicitis and as a predictor of complicated appendicitis: a meta-analysis. ann med surg (lond). 2021;66:102448. 21. boshnak n, boshnaq m, elgohary h. evaluation of platelet indices and red cell distribution width as new biomarkers for the diagnosis of acute appendicitis. j invest surg. 2018;31(2):121-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e29 or i g i n a l re s e a rc h association between neutrophil density and survival in trauma patients admitted to the intensive care unit; a retrospective cohort study mohebat vali1, shahram paydar2, mozhgan seif3, maryam hosseini2, pardis basiri5, golnar sabetian6, haleh ghaem3∗ 1. student research committee, shiraz university of medical sciences, shiraz, iran. 2. trauma research center, shahid rajaee (emtiaz) trauma hospital, shiraz university of medical sciences, shiraz, iran. 3. non-communicable diseases research center, department of epidemiology, school of health, shiraz university of medical sciences, shiraz, iran. 4. trauma research center, shahid rajaee (emtiaz) trauma hospital, shiraz university of medical sciences, shiraz, iran. 5. department of computer science and engineering and it school of electrical engineering and computer, shiraz university, shiraz, iran. 6. anesthesiology and critical care trauma research center, shiraz university of medical sciences, shiraz, iran. received: january 2023; accepted: february 2023; published online: 3 april 2023 abstract: introduction: altered immune responses, in particular neutrophil changes, are perceived to play a key role in immune responses to trauma. this study aimed to evaluate the association of neutrophil changes with patients’ survival in severe trauma cases. methods: the current retrospective cohort study was conducted using data from patients admitted in the intensive care unit (icu) of a trauma center in shiraz, iran, between 2016 and 2021. patients were divided into three groups (i.e., normal, neutropenia, and neutrophilia) based on neutrophil count at the time of icu admission, and the association of neutrophil count with in-hospital mortality was analyzed. results: 2176 patients with the mean age of 37.90 ± 18.57 years were evaluated (84.04% male). the median trauma severity based on injury severity score (iss) in this series was 9 (4 -17). patients were divided in to three groups of neutrophilia (n = 1805), normal (n = 357), and neutropenia (n = 14). there were not any significant differences between groups regarding age distribution (p = 0.634), gender (p = 0.544), and trauma severity (p = 0.197). the median survival times for the normal, neutropenia, and neutrophilia groups were 49 (iqr: 33 -47) days, 51 (iqr: 851) days, and 38 (iqr: 26 52) days, respectively (p = 0.346). the log-rank test showed a statistically significant difference between the three groups adjustment for iss (p ≤ 0.001). for each unit increase in iss, the hazard ratio increased by 2%. in iss 9-17, the hazard ratio increased by 11% compared to iss<4. also, in iss>17, the hazard ratio increased by 76% compared to iss<4 in icu-hospitalized patients. conclusion: in general, the findings of the present study showed that the survival rate of patients in the normal group after iss adjustment was higher than the other two groups. also, the cox model showed that the mortality risk ratio in the neutropenia group was 15 times higher than the normal group. keywords: neutrophils; survival; neutropenia; wounds and injuries; multiple trauma; trauma severity indices cite this article as: vali m, paydar s, seif m, hosseini m, basiri p, sabetian g, ghaem h. association between neutrophil density and survival in trauma patients admitted to the intensive care unit; a retrospective cohort study. arch acad emerg med. 2023; 11(1): e29. https://doi.org/10.22037/aaem.v11i1.1990. ∗corresponding author: haleh ghaem; department of epidemiology, school of health, shiraz university of medical sciences, shiraz, iran. tel: +98 71 37256007, email: ghaemh@sums.ac.ir, orcid: https://orcid.org/0000-00019564-392x. 1. introduction recently, who has estimated that trauma accounts for 5.8 million mortalities, annually (1, 2). in recent years, traumacaused mortalities have substantially declined owing to advances in treatment approaches, particularly in patients under blood clot and blood loss treatments. however, secondary complications such as sepsis, multiple organ failure (mof), and nosocomial infections may harm trauma pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vali et al. 2 tients or even cause death (3). neutrophils constitute 60-70% of circulatory leukocytes in the body, playing a key role in innate immunity and host defense against invading pathogens, as well as eliciting inflammation-induced tissue damage (4). in healthy individuals, circulatory neutrophils are primarily naïve cells, which are subsequently activated by recognizing damage-associated molecular patterns (damps) through their pathogen-associated molecular patterns (pamps), thereby maintaining the immune system homeostasis (5). upon inflammation, neutrophils properly respond to microenvironmental signals and obtain distinct functional phenotypes, commonly referred to as neutrophil heterogeneity (6, 7). besides, trauma can affect neutrophils (8). indeed, neutrophils are the first line of defense against microbial pathogens and trauma and commence inflammatory responses. trauma-induced modulations in neutrophils, ultimately lead to post-traumatic complications e.g., multiple organ failure and acute respiratory distress syndrome (8). at a wide range of time points after traumatic injury, ex vivo studies have reported significant changes in many neutrophil functions (9-14) that probably contribute to the development of secondary complications. experimental studies indicate a direct relationship between trauma severity and the consequent tissue impairment and/or neutrophil dysfunction (15). in addition, depending on the stage of injury, neutrophils can contribute to repair mechanisms or exacerbate the pathophysiology of trauma (16). a retrospective study (17) explored neutrophils’ involvement in severe trauma to uncover the link between trauma severity and neutrophils’ phenotype/function. however, given that we only obtained the basic blood test information on neutrophils’ percentage from patients at the time of admission, we were encouraged to investigate the impact of neutrophil density on trauma patients’ survival. for this purpose, we attempted to evaluate neutrophil counts in patients with adjusted injury severity to determine neutrophils’ overall effects. as mentioned, there is an important balance between proinflammatory and anti-inflammatory systems in the immune response to trauma. the imbalance between these systems plays an important role in the post-injury outcomes of critically ill patients (18, 19). understanding the link between neutrophil dysfunction (neutropenia, or neutrophilia) and patients’ survival may yield appropriate early biomarkers for clinical applications and treatment of trauma patients. therefore, this study aimed to evaluate the association of neutrophil changes with patients’ survival in severe trauma cases admitted to intensive care unit (icu). 2. methods 2.1. study design and setting the current retrospective cohort study was carried out using data from trauma patients admitted to icu of shahid rajaee hospital (imtiaz), shiraz, iran, between 2016 and 2021. patients were divided into three groups (i.e., normal, neutropenia, and neutrophilia) based on neutrophil count at the time of icu admission and the association of neutrophil count with in-hospital mortality were analyzed. the ethics committee approved this study at shiraz university of medical sciences (ir.sums.scheanut.rec.1400.006). this information was collected for the purpose of research by the trauma research center of shahid rajaei hospital using the patients’ files; therefore, due to the nature of the research, informed consent was obtained from the patients themselves or their legal guardians upon the arrival of the patients. in addition, the private medical information of the patients remained confidential, and the researchers were not provided with the name, surname, and national code for the confidentiality of the patients’ information 2.2. participants all trauma patients over 18 years old, who presented to the icu of the mentioned hospital were enrolled. patients who were transferred to another hospital or whose final outcomes regarding in-hospital mortality or survival was not available were exclude. additionally, all women regardless of pregnancy status were included in the study, but those who died in the emergency department and patients who died within 6 hours of hospital admission were excluded from the study. also, patients were followed for the duration of their hospital stay or at subsequent hospital visits, but were not specifically followed for post-discharge trauma deaths. 2.3. data gathering the variables included the demographic information (age and gender), hospitalization information (date and time of icu admission and discharge), patients’ outcome at the time of discharge from icu (in-hospital mortality), injury mechanism (accidents or others), patients’ consciousness status at the time of icu admission (glasgow coma scale (gcs), pupil 1 and 2), the injury severity score )iss), patients’ vital signs (heart rate [hr], respiratory rate [rr], systolic blood pressure [sbp], and diastolic blood pressure [dbp]), and arterial blood gas analysis (blood acidity [ph], arterial blood carbon dioxide [pco2], arterial blood oxygen [pao2] levels and using artificial respiration device, fio2), as well as laboratory information (blood sugar [bs], blood urea nitrogen [bun], creatinine [cr], sodium [na], potassium [k], prothrombin time pt], partial thromboplastin time [ptt], international normalized ratio [inr], hemoglobin, lymphocyte, fibrinogen, white blood this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e29 table 1: patients’ baseline characteristics characteristic neutropenia n = 14 normal n = 357 neutrophilia n =1805 pa age (year) mean ± sd 33.50 ± 15.35 38.21 ± 18.43 38.26 ± 18.68 0.634 gender female 1 (0.29) 61 (17.63) 284 (82.08) 0.544 male 13 (0.71) 296 (16.17) 1521 (83.11) cause of injury accidentsd 10 (0.61) 261 (16.00) 1360 (83.38) 0.610 othere 4 (0.74) 96 (17.71) 442 (81.55) length of stay, median (iqr) icu 3 (0.75 8.25) 3 (1 9) 6 (2 12) 0.0001 hospital 2.5 (1.75 6.25) 7 (2 17) 10 (4 38) 0.0001 vital signs on arrival, median (iqr) o2 saturation (%) 93 (90.75 96.25) 93 (89 96) 93 (90 96) 0.917 sbp (mmhg) 116.5 (103 137.75) 123 (107 138.75) 127 (110 139) 0.037 dbp (mmhg) 75 (59.5 87.5) 78 (65.5 87) 80 (70 88) 0.063 gcs 13 (7 15) 13 (7 15) 12 (7 15) 0.318 rr (/minute) 19.5 (17.75 21.25) 20 (17 22) 20 (17 22) 0.974 pr (/minute) 104.14 (21.73) 104.04 (23.64) 101.45 (24.42) 0.174 pupils (first hour) responsive 13 (0.71) 314 (17.05) 1515 (82.25) 0.314 unresponsive 0 (0.00) 24 (14.04) 147 (85.96) iss median (iqr) 9 (8 16.5) 9 (4 17.25) 12 (5 18) 0.197 intubated yes 4 (0.54) 113 (15.13) 630 (84.34) 0.863 no 8 (0.71) 175 (15.57) 941 (83.72) a: comparison of the three groups (one-way anova or kruskal–wallis) or chi square d: traffic accidents and accidents include: pedestrian accident, motorcyclist accident, and car accident. e: others include: falling from a height, being hit by a sharp object, being hit by a bullet, assault, falling to the ground, continuing treatment, suicide, and self-mutilation. iqr: interquartile range; iss: injury severity score; sbp: systolic blood pressure, dbp: diastolic blood pressure; gcs: glasgow coma scale; rr: respiratory rate; pr: pulse rate; icu: intensive care unit; sd: standard deviation. for neutrophils, 45-75% of white blood cell count was considered normal, while less than 4% and more than 75% were considered neutropenia and neutrophilia, respectively. table 2: multiple cox regression of survival in trauma patient variable hazard ratio 95% ci p value injury severity score 1.02 (1.00,1.05) 0.042 ph 0.42 (0.21,0.82) 0.011 o2 saturation 0.990 (0.982,0.999) 0.044 groups normal (ref ) neutropenia 15.06 (1.809,125.40) 0.012 neutrophilia 0.92 (0.42, 2.00) 0.843 ci: confidence interval. test of proportional hazards assumption based on schoenfeld residuals (phtest) = 0.726. count [wbc], and neutrophils count) based on patients’ profile. patients were divided into three groups based on their circulatory neutrophil count. for neutrophils, 45-75% of wbc was considered normal, while less than 45% and more than 75% were considered neutropenia and neutrophilia, respectively. to determine the final status of the patients as our preferred outcome, the patients were followed up until the last day of hospitalization and if the patients were discharged from the hospital alive, we considered them "alive" and if the doctor diagnosed and issued a death certificate, we considered them "dead". in addition, we excluded the patients who were transferred to another treatment center due to the inability to follow up their condition. mv, in collaboration with trauma research center, was responsible for data gathering. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vali et al. 4 figure 1: kaplan-meier diagram in trauma patients adjusted for injury severity score (iss) in three groups of neutropenia, normal and neutrophilia. ais: abbreviated injury scale. 2.4. statistical analysis we analyzed the data normality using the kolmogorovsmirnov test and related graphs. for quantitative variables with normal distribution, mean and standard deviation (sd) were employed, and for non-normal data, the median and percentiles were reported. besides, for qualitative variables, frequency and percentage were utilized. analysis of variance (anova) or kruskal–wallis test was also exploited to compare quantitative variables between the normal, neutropenia, and neutrophilia groups. furthermore, sidak post hoc or mann–whitney u test was used for subsequent comparison between the groups. in addition, the chi-square test was utilized to compare qualitative variables between the groups. to draw graphs. in addition, for survival analysis, kaplan-meier adjusted for the iss and log-rank were employed to compare the groups. finally, both simple and multiple cox regression analyses were utilized to explore factors associated with the survival of icu-hospitalized trauma patients. then, the proportional hazards assumption test based on the schoenfeld residuals (phtest) was utilized to determine the proportional hazards assumption. all analyses were performed using stata 12 software with a significance level of p ≤ 0.05. 3. results 3.1. baseline characteristics of studied cases data was collected from 3782 trauma patients hospitalized in the intensive care unit. after the exclusion of patients under 18 years of age, patients transferred to another hospital, patients whose final status (death or aliveness) was not known, and patients with missing data, 2176 patients were finally evaluated. table 1 depicts the participants’ characteristics. patients’ average age was 37.90±18.57 (range 18-100) years (84.04% male). the median trauma severity based on iss in this series was 9 (4 -17) and the main cause of hospitalization in more than 70% of the patients was traffic accidents (pedestrian, motorcyclist, and car accidents). patients were divided in to three groups of neutrophilia (n = 1805), normal (n = 357), and neutropenia (n = 14) based on total neutrophil count at the time of admission to icu. there were not any significant differences between groups regarding age distribution (p = 0.634). gender (p = 0.544), and trauma severity (p = 0.197). in laboratory data, a statistically significant difference was observed between the groups only regarding the amount of k (p = 0.002), ptt (p = 0.0022), wbc (p ≤ 0.001), hb (p = 0.0026), and lymphocytes (p ≤ 0.001). 3.2. survival analysis the median overall survival time was 40 (iqr: 22-51) days. also, the median survival time for the normal, neutropethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e29 nia, and neutrophilia groups was 49 (iqr: 33 -47) days, 51 (iqr: 851) days, and 38 (iqr: 26 52) days, respectively (p = 0.346). figure 1 shows the kaplan-meier diagram for the groups adjusted for the iss. also, the log-rank test did not exhibit a statistically significant difference between the normal and neutropenia groups (p = 0.581). likewise, no statistically significant difference was shown between the normal and neutrophilia groups (p = 0.437). however, the log-rank test showed a statistically significant difference between the three groups despite adjustment for iss (p ≤ 0.001). multiple cox analysis results are shown in table 2. as the table depicts, for each unit increase in iss, the hazard ratio increased by 2%. in iss 9-17, the hazard ratio increased by 11% compared to iss<4. also, in iss>17, the hazard ratio increased by 76% compared to iss<4 in icu-hospitalized patients. in addition, for each unit increase in blood ph, the hazard ratio decreased by 58%. in this sense, neutropenia had 15.06 times higher hazard ratio than the normal group. 4. discussion this retrospective study evaluated trauma patients’ survival rate based on their neutrophil count (i.e., normal, neutropenia, and neutrophilia). our findings denoted that after adjustment for iss, the normal group’s survival rate is greater than the neutropenia and neutrophilia groups. furthermore, the cox model revealed that each unit increase in the iss increases the hazard ratio. consistently, this model revealed that neutropenia increases the hazard ratio up to 15 times. neutrophils play a major role in inflammatory responses upon the occurrence or following traumatic injuries. ensuing the trauma, neutrophils undergo significant functional changes, causing a rapid efflux of neutrophils from the bone marrow into the circulation (20). in compliance with previous studies, we showed that neutrophilia is more prevalent in the first 24 hours’ post-trauma compared to neutropenia. indeed, neutrophilia is the first post-trauma event due to the endogenous release of cortisol and catecholamine, resulting in neutrophil production and subsequent release from the bone marrow (21, 22). however, numerous studies have proposed that the increased release of neutrophils into the circulation may lead to the emergence of immature and dysfunctional neutrophil s(21-25), ultimately, resulting in peripheral tissue damage and multiple organ dysfunctions (mods) (26-29). hence, neutrophilia might not be correlated with the improved survival of traumatic patients as it was revealed that the normal group patients lived much longer than the neutrophilia group patients. on the other hand, neutropenia increased mortality more than 15 times in critical trauma patients. the low survival of neutropenia patients could be attributed to neutrophil dysfunction, thereby enhancing hospitalized trauma patients’ sensitivity to healthcare-associated infections (30). also, in a previous review study, by investigating the effect of trauma on neutrophil phenotype with the main purpose of using this knowledge to investigate the predictive potential of neutrophil changes on secondary complications in patients with traumatic injuries, they came to the same conclusion that changes in the markers and functions of neutrophils may be potential biomarkers that predict the outcome of trauma patients (17). in this sense, manipulating neutrophil frequency to improve patients’ survival might be controversial. however, boosting neutrophils’ germicidal and anti-infective capacity could be quite appealing. of note, uncontrolled neutrophil hyperactivation may lead to significant tissue impairment, thereby contributing to development of acute respiratory distress syndrome (ards) and mof. on the contrary, suppressing neutrophils’ inflammatory response shortly after a traumatic insult to reduce immunity-induced tissue impairment may predispose patients to microbial infections. therefore, developing strategies to create an equilibrium between these issues is urgently required to assist patients’ recovery by modifying the immune response. 5. limitations the current study has several strengths such as including a large number of trauma patients. in addition, this study was conducted in the largest trauma center in southern iran, which is a specialized center for trauma. taking potential confounders into account (e.g., the iss), as well as using laboratory information and abg are other advantages of the current study. nonetheless, the shortcomings of the current study should not also be neglected. for example, the retrospective design of study has its limitations. in this regard, we suggest the prospective investigation of neutrophils’ effects on patients’ survival in future studies. also, we were not able to study neutrophil phenotypes, therefore, investigating their phenotypes is encouraged. furthermore, our data on neutrophils was based on wbc percentages, hence, we suggest these data to be analyzed based on wbc number/l. also, we reported neutrophils’ normal range from different sources, which might have affected the results. however, we chose neutrophils’ normal range based on hospital kits, which are used for correcting differential reports. also, for neutrophil measurement, we did not have data on neutrophil counts at different time points after trauma, which should be taken into account in future studies. finally, neutrophil changes in icu-hospitalized patients also require further investigation. 6. conclusion overall, the findings of the current study revealed that patients’ survival rate in the normal group after adjustment for iss was higher than the neutropenia and neutrophilia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. vali et al. 6 groups. also, the cox model showed that the hazard ratio in the neutropenia group was 15 times higher than that of the normal group. hence, fixing neutrophil disorder may plummet the hazard ratio in trauma patients. indeed, one of the core findings of the current review is that the survival rate can be predicted using neutrophil count, which can be measured using a simple blood sample. in addition, neutrophil count could have a predictive value for the risk assessment of trauma patients. moreover, we suggest neutrophil changes during patients’ icu hospitalization to be further investigated. 7. declarations 7.1. acknowledgments this article was a part of mohebat vali’s ph.d. thesis, approved and financially supported by the research vice-chancellor of shiraz university of medical sciences (grant no. 1400-10-5-23391). the ethics committee approved this study at shiraz university of medical sciences (ir.sums.scheanut.rec.1400.006). we would also like to express our special thanks to the efforts and cooperation of the staff of rajaei hospital, including mrs. mrs. saadat jo, mrs. shayan, and mrs. mohammadi who helped us a lot in collecting data. 7.2. competing interests statement the authors of this study declared no competing interests. 7.3. fundings and supports this article was a part of mohebat vali’s ph.d. thesis, approved and financially supported by the research vicechancellor of shiraz university of medical sciences (grant no. 1400-10-5-23391). 7.4. authors’ contribution hg is the lead author and guarantor and contributed to interpreting the data and revising the manuscript. mv and shp planned the study and led the drafting and revising of the manuscript. mv, ms, mh, shp, pb and gs contributed to interpreting the data and drafting and revising the manuscript. all authors approved the submitted version of the manuscript. all authors have contributed to the preparation of the manuscript, have read, and approved the submitted manuscript. all authors listed meet the authorship criteria according to the latest guidelines of the international committee of medical journal editors and agree with the manuscript. the work is original and not under consideration by any other journal. 7.5. data availability the data that support the findings of this study are available from the corresponding author, [hgh], upon reasonable request. 7.6. ethics approval and consent to participate the ethics committee approved this study at shiraz university of medical sciences (ir.sums.scheanut.rec.1400.006). informed consent was obtained from all subjects or their legal guardians to use their data for research. references 1. lord jm, midwinter mj, chen y-f, belli a, brohi k, kovacs ej, et al. the systemic immune response to trauma: an overview of pathophysiology and treatment. lancet. 2014;384(9952):1455-65. 2. rossaint r, bouillon b, cerny 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brohi k, kovacs ej, et al. the systemic immune response to trauma: an overview of pathophysiology and treatment. lancet. 2014;384(9952):1455-65. 28. botha aj, moore fa, moore ee, sauaia a, banerjee a, peterson vm. early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. j trauma. 1995;39(3):411-7. 29. visser t, pillay j, koenderman l, leenen lp. postinjury immune monitoring: can multiple organ failure be predicted? curr opin crit care. 2008;14(6):666-72. 30. papia g, mclellan ba, el-helou p, louie m, rachlis a, szalai j-p, et al. infection in hospitalized trauma patients: incidence, risk factors, and complications. j trauma. 1999;47(5):923. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 26 emergency (2014); 2 (1): 26-29 original research synergistic effects of citalopram and morphine in the renal colic pain relief; a randomized clinical trial mehrdad esmailian, mehdi keshavarz* department of emergency medicine, isfahan university of medical sciences, isfahan, iran abstract introduction: although the synergistic effects of opioids and other analgesic drugs such as non-steroidal antiinflammatory drugs (nsaids) have been established in relieving acute pain due to renal calculi, no studies today have evaluated the concomitant administration of opiates and other drugs with analgesic effects, such as serotonin re-uptake inhibitors. considering the high prevalence of renal colic, the present study was carried out to compare the effect of concomitant prescription of morphine and a placebo with that of morphine and citalopram on the management of acute pain due to renal calculi. methods: the present double-blind randomized clinical trial was carried out from october 2012 to march 2013 in the al-zahra educational hospital in isfahan, iran. 90 patients with acute renal colic pain were randomly divided into two groups of 45 subjects. the subjects in one group received morphine/ placebo and another one morphine/citalopram. the patients’ pain severity was determined by visual analogue scale (vas) before and 20 minutes after administration of medications. in case of persistent pain, the second or even third dose was administered and the pain severity was once again determined. data were analyzed with stata 11.0 using chi-squared, two-way anova, bonferroni post hoc test, and log rank test. results: the decrease in pain severity in the morphine/citalopram group was significantly compared to the morphine/placebo group and the time before administration of the medications (p<0.001). in contrast, administration of morphine/placebo did not have a significant effect on pain severity at this interval (p=0.32). kaplan-meier curve showed that the first injection was successful in relieving pain in 15 (33.3%) and 26 (57.8%) subjects in the morphine/placebo and morphine/citalopram groups, respectively. the second injection of these medications resulted in therapeutic success in 35 (87.8%) and 42 (95.6%) subjects in the above groups, respectively. log rank test showed a significant difference in the treatment success between the two groups (p=0.001). conclusion: it seems that the combination of citalopram and morphine sulfate causes increased efficacy and higher success rate in pain control of patients presented to the emergency department with a complaint of renal colic. key words: pain management; renal colic; morphine; citalopram; emergencies cite this article as: esmailian m, keshavarz m. synergistic effects of citalopram and morphine in the renal colic pain relief; a randomized clinical trial. emergency. 2014;2(2):26-9. introduction:1 enal colic is usually manifested clinically as a very painful and troublesome condition which appears unilaterally on the flank to the groin suddenly or periodically (1, 2). the condition afflicts 512% of the population in industrial societies at least once in their life and its recurrence rate is approximately 50% (1). the pain is usually attributed to contraction of ureter soft muscles in response to the presence of stone (3-5). therefore, the most important consideration in the emergency management of renal colics is pain control/relief (5, 6). various therapeutic strategies are employed to alleviate the pain due to renal calculi and some studies have recommended the use of nsaid, *corresponding author: mehdi keshavarz; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989136470851; fax:+983117923445 email: drmke2024@gmail.com received: 14 january 2014; accepted: 5 february 2014 especially ketorolac, as the first analgesic for renal calculi (5, 7-10). however, disadvantages such as lack of availability, high cost, the risk of gastrointestinal hemorrhage, and acute renal insufficiency have led to a greater use of opioids such as meperidine and morphine or their concomitant use in clinical settings compared to nsaids (1, 11, 12). on the other hand, there is an ample evidence in relation to pain relief with the use of serotonin re-uptake inhibitors such as citalopram in patients with acute and chronic renal insufficiency, in cases of visceral pain, heat sensitivity, thermal pain, peritoneal dialysis, peritonitis and neuropathic injuries (13, 14). although the synergistic effects of opioids such as morphine and the group of analgesics such as nsaids have been established on relieving acute pain due to renal stones, no studies today have evaluated the effects of concomitant administration of opioids and other analgesic agents, such as serotonin re-uptake inr this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 27 esmailian et al hibitions. therefore, the present study was undertaken to evaluate the presence or absence of synergistic or additive analgesic effect of morphine and citalopram on relieving acute renal stone pain. methods: study design and setting the present double-blind randomized clinical trial was carried out during a six-month period from october 2012 to march 2013 in the emergency department of al-zahra hospital, isfahan, iran. the protocol of the study was prepared based on helsinki declaration and approved by ethics committee of isfahan university of medical sciences. the study was registered in iranian registry of clinical trial (irct2014020812072n1). all patients signed consent form before including to the study. participants the subjects were patients with acute renal colic, referring to the emergency department of al-zahra hospital. the inclusion criteria consisted of an age range of 1855, a clinical diagnosis of acute colicky pain, pain severity of 7-10 based on visual analogue scale (vas), and patients’ consent form to participate in the study. the exclusion criteria consisted of pregnancy or suspected of being pregnant, contraindication in relation to taking morphine and citalopram based on drug catalog, a history of dependence on opioids or ssris, receiving an analgesic during a six-hours period before presentation, peritonitis or peritoneal symptoms and signs, any disease preventing communication, and patient’s decision to leave the study. intervention all the patients underwent a urine analysis and an ultrasound examination. the final diagnosis was reached in each patient based on initial clinical diagnosis using the examinations above. the patients were randomly assigned to two groups. the subjects in group one received an intravenous injection consisting of 5 mg of morphine sulfate plus placebo (normal saline with the same volume as that in group two) and subjects in group two received an intravenous injection consisting of 5 mg of morphine sulfate plus 20 mg of citalopram. during the study period, none of the patients, physicians and nurses, and the medical care team members were aware of the study procedures. preparation and injection of medications were carried out by two nurses; the nurses prepared the medications were blind to drugs of each patient. all the syringes had the same shape. randomization and registration of data were carried out by the chief researcher who was the only person aware of the study procedures. in order to confirm the diagnosis, all the patients were subjected to an ultrasound examination of kidneys and the urinary tract. the ultrasonography was not performed for patients with a documented history of renal calculi or patients recovering from renal calculi and referring with a similar episode. visualization of a renal stone by a radiologist during ultrasound examination or a report of hydronephrosis on the painful side confirmed the diagnosis. passage of stone through the urethra and direct visualization of stone confirmed the diagnosis, too. the medications were administered intravenously in the same manner for all the patients and each of them received a proper medications dose based on a timetable. any drug side effect was managed by standard protocols of the emergency department. statistical analyses the sample size in the present study was calculated at 45 subjects in each group, by considering a 95% confidence interval, an 80% power of the test, the variance of pain severity 1.7, and the minimum significant difference 0.8. data were analyzed using stata ver. 11.0. independent t-test and chi-squared test were used to evaluate the quantitative and qualitative variables, respectively. two-way anova and bonferroni post hoc test were applied to assess interand intra-group differences in pain severity based on vas at study intervals. kaplan-meier estimates were used to evaluate treatment success and log rank test to compare the treatment regiments. to this end, treatment success was defined as a decrease in pain severity at least three points on vas. statistical significance was defined at p<0.05. results: ninety patients with acute colicky pain were equally assigned to two groups for treatment with morphine + placebo and morphine/citalopram. the mean ages of the subjects in two groups were 35.36±9.5 and 35.56±10.4 years, respectively (p=0.92). in the morphine/placebo and morphine/citalopram groups, 33 (73.3%) and 32 (71.1%) subjects were male, respectively (p=0.92). the mean vas at the time of admission in the morphine/placebo and morphine/citalopram groups were 7.53±1.66 and 7.07±1.85, respectively (p=0.22). twenty minutes after the first injection, the mean vas decreased to 6.4±2.3 and 4.0±3.1 in the morphine/placebo and morphine/citalopram groups, respectively. the decrease in pain severity in the morphine/citalopram group was significantly compared to the morphine/placebo group and the time before administration of the medications (baseline) (p<0.001). in contrast, administration of morphine and placebo did not have a significant effect on pain severity at this interval (p=0.32). the mean pain severity 20 minutes after the second injection meaningfully decreased (40 minutes after the first injection) in the morphine/citalopram group [mean (sd)= 1.6 (1.6); p< 0.001] and in the morphine/placebo group [mean (sd)= 2.31 (1.72); p<0.001]. pain severity was not considerably different between the two study groups (p>0.99). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 28 emergency (2014); 2 (1): 26-29 the third injection did not have any extra effect on pain intensity in both groups (p>0.99) (figure 1). two-way anova showed that the therapeutic interventions resulted in a significant decrease in pain severity (df: 1.7; f=66.9; p<0.001). kaplan-meier curve showed that the first injection was successful in relieving pain in 15 (33.3%) and 26 (57.8%) subjects in the morphine/ placebo and morphine/citalopram groups, respectively. the second injection of these medications resulted in therapeutic success in 35 (87.8%) and 42 (95.6%) subjects in the above groups, respectively. log rank test showed a remarkable difference in the treatment success between the two groups (p=0.001) (figure 2). discussion: based on the findings of present study, combination of morphine sulfate and citalopram has significantly higher success rate in pain control of renal colic during the first 20-minute period in comparison to morphine alone. however, administration of morphine and placebo did not have a noteworthy effect on pain severity at this interval. there were no meaningful differences in the second and third dose administrations between two groups regarding changes in pain severity (figure 1). but, the results of the log rank test revealed a significantly higher success rate in morphine/citalopram group at the same time. it means that, although the two groups were able to equal changes in pain severity during a 60-minute period, but the failure rate was considerably higher in patients received morphine alone. previous studies have shown that use of morphine results in an increase of serotonin levels in the brain; also, use of citalopram increases serotonin concentration by inhibiting its re-uptake (15). on the other hand, the tranquilizing effect of citalopram helps relieving pain in these patients. sacerdote et al. concluded that the analgesic effect of some antidepressant seems to be related to an activation of the endogenous opioid system mediated by serotonin (16). therefore, it seems that the combination of a serotonin re-uptake inhibitor and morphine sulfate have synergistic effects regarding pain control. since citalopram has a minimum side effects compared to other inhibitors of serotonin reuptake inhibitors, it could be considered as a suitable choice for this object. campo and their colleague revealed the potential effects of citalopram for functional pediatric recurrent abdominal pain control (17). a randomized double-blind study showed a moderate analgesic effect of citalopram in patients with pain disorder and declared that it appears to be not correlated to changes in depressive scores (18). also, citalopram had a positive effect on chronic pelvic pain control and relieving peripheral neuropathic pain in diabetic patients (19, 20). the present study showed that citalopram in combination with morphine causes to increase the efficacy of morphine in relieving the pain of renal colic. further studies are needed to evaluate of action mechanisms and potential complications limitation although the vas is a standard scoring system for evaluation of pain severity, the use of functional (21) and behavioral (22) indices, as an adjunct to vas, could be more accurate. however, the study power of 99% made the findings of the study valid. conclusion: it seems that the combination of citalopram and mor figure 1: time trend of pain severity in the morphine/placebo and morphine/citalopram groups. data were presented as means and standard errors. * significant difference compared to the period before treatment at p<0.001; # significant difference with same time in the morphine/placebo group at p<0.001.  figure 2: the kaplan-meier curve to show the success rate in patients’ underling treatment with two drug regimens of morphine + placebo and morphine + citalopram. log rank test showed a significant difference in treatment success between the two groups (p=0.001).  *# * * 0 1 2 3 4 5 6 7 8 9 before treatment 20 minute 40 minute 60 minute p a in s c o r e ( v a s ) time morphine + placebo morphine + citalopram 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 p e r c e n ta g e o f fa il u r e 45 19 (42.2%) 2 (4.4%) 2 (4.4%)morphine + citalopram 45 30 (66.7%) 10 (22.2%) 10 (22.2%)morphine + placebo number of failure 0 20 40 60 time (minute) morphine + placebo morphine + citalopram kaplan-meier failure estimates this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 29 esmailian et al phine sulfate causes to an increased efficacy and higher success rate in pain control of patients presented to the emergency department with a complaint of renal colic. acknowledgments: we acknowledge all staffs of emergency department and dialysis unit of al-zahra hospital, isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of international committee of medical journal editors. references: 1. curhan gc, willett wc, rimm eb, stampfer mj. family history and risk of kidney stones. j am soc nephrol. 1997;8(10):1568-73. 2. safdar b, degutis lc, landry k, vedere sr, moscovitz hc, d’onofrio g. intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. ann emerg med. 2006;48(2):173-81. 3. labrecque m, dostaler l-p, rousselle r, nguyen t, poirier s. efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic: a meta-analysis. arch intern med. 1994;154(12):1381-7. 4. segura jw, preminger gm, assimos dg, et al. ureteral stones clinical guidelines panel summary report on the management of ureteral calculi. j urol. 1997;158(5):1915-21. 5. holdgate a, pollock t. nonsteroidal anti-inflammatory drugs (nsaids) versus opioids for acute renal colic. cochrane database syst rev. 2004;1:cd004137. 6. teichman jm. acute renal colic from ureteral calculus. n engl j med. 2004;350(7):684-93. 7. tramŕr dm, williams j, carroll d, wiffen p, moore r, mcquay h. comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. acta anaesthesiol scand. 1998;42(1):71-9. 8. cevik e, cinar o, salman n, et al. comparing the efficacy of intravenous tenoxicam, lornoxicam, and dexketoprofen trometamol for the treatment of renal colic. am j emerg med. 2012;30(8):1486-90. 9. hemrika d, bossuyt p. ketorolac versus morphine for severe pain. trial. 1997;350:774-9. 10. schröder w, vry j, tzschentke tm, jahnel u, christoph t. differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. eur j pain. 2010;14(8):814-21. 11. bomholt sf, mikkelsen jd, blackburn-munro g. antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. neuropharmacology. 2005;48(2):252-63. 12. o'connor a, schug sa, cardwell h. a comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. j accid emerg med. 2000;17(4):261-4. 13. tartau l. the effects of citalopram and escitalopram in visceral pain and behavioral models in mice: experimental researches. eur j pain. 2009;13:s56. 14. reinhart dj. minimising the adverse effects of ketorolac. drug saf. 2000;22(6):487-97. 15. rafieian-kopaei m, gray am, spencer ps, sewell rd. contrasting actions of acute or chronic paroxetine and fluvoxamine on morphine withdrawal-induced place conditioning. eur j pharmacol. 1995;275(2):185-9. 16. sacerdote p, brini a, mantegazza p, panerai ae. a role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs. pharmacol biochem behav. 1987;26(1):153-8. 17. campo jv, perel j, lucas a, et al. citalopram treatment of pediatric recurrent abdominal pain and comorbid internalizing disorders: an exploratory study. j am acad child adolesc psychiatry. 2004;43(10):1234-42. 18. aragona m, bancheri l, perinelli d, et al. randomized double-blind comparison of serotonergic (citalopram) versus noradrenergic (reboxetine) reuptake inhibitors in outpatients with somatoform, dsm-iv-tr pain disorder. european journal of pain. 2005;9(1):33-8. 19. brown cs, franks as, wan j, ling fw. citalopram in the treatment of women with chronic pelvic pain: an open-label trial. j reprod med. 2008;53(3):191-5. 20. qinying c, zhixiong t, jinwei w. therapeutic effects of citalopram on alleviating pain of peripheral neuropathy in type 2 diabetic patients. med j chin pla. 2008;3:32-8. 21. jensen mp, smith dg, ehde dm, robinsin lr. pain site and the effects of amputation pain: further clarification of the meaning of mild, moderate, and severe pain. pain. 2001;91(3): 317-22. 22. farrar jt, portenoy rk, berlin ja, kinman jl, strom bl. defining the clinically important difference in pain outcome measures. pain. 2000;88(3):287-94. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 106 emergency (2016); 4 (2): 106-107 casr report peganum harmala (aspand) intoxication; a case report rezvan sadr mohammadi1, reza bidaki 2*, fazlollah mirdrikvand3, seyyed nader mostafavi yazdi 4, pouria yazdian anari5 1. department of psychology, kar higher education institute, rafsanjan, iran. 2. department of psychiatry, research center of addiction and behavioral sciences, shahid sadoughi university of medical sciences, yazd, iran. 3. department of psychology, lorestan university, khorram abad, iran. 4. department of toxicology and legal psychiatry, shahid sadoughi university of medical sciences, yazd, iran. 5. research committee, shahid sadoughi university of medical science, yazd, iran. *corresponding author: reza bidaki; department of psychiatry, shahid sadoughi university of medical sciences, yazd, iran. tel: +983532632004; fax: +983532623555; email: reza_bidaki@yahoo.com received: june 2015; accepted: august 2015 abstract there are several reports in the literature indicating a great variety of pharmacological effects for peganum harmala or aspand such as sedative anti-bacterial, anti-fungal, antiviral and antiprotozoal. some people believe that can be used for treatment of some organic or psychiatric disorders. we introduce a woman with history of long time constipation that was disappointed in novel medical treatment and decided to use comminuted aspand to relieve her problem .two hours after use, the intoxication symptoms manifested as blurred vision, phonophobia, floating feeling, and tinnitus ringing. here we report the treatment process and outcome of this case. keywords: peganum; harmine; poisoning; emergency department cite this article as sadr mohammadi r, bidaki r, mirdrikvand f, mostafavi yazdi sn, yazdian anari p. peganum harmala (aspand) intoxication; a case report. emergency. 2016; 4(2):106-107. introduction: eganum harmala commonly known as syrian rue or “aspand” is widely used in middle east and north africa (1, 2). various parts of harmala are used in traditional medicine. the pharmacologically active compounds of this herb are several alkaloids, which are found especially in the seeds and roots (3). it was used as sedative in restless and agitated patients. its seeds are known to possess hypothermic, hallucinogenic and anti-oxidative properties (3, 4). there are several reports in the literature indicating a great variety of pharmacological effects for this plant such as sedative anti-bacterial, anti-fungal, antiviral and antiprotozoal (5, 6). it is also used illegally as an abortifacient agent (4). aspand intoxication is among very rare causes of intoxication, with a mortality rate of about 6%. nevertheless in some countries, it makes up 4.6% of all plant intoxications (7). ingestion is the main route of intoxication, but inhalation and fumigation are also mentioned (8). there are few studies on related symptoms following consumption and intoxication with aspand (9-11). here we report a case of harmala intoxication presented to emergency department with psychiatric complaint. case presentation: the patient was a 54-year-old woman presented to the emergency department with severe vomiting and abrupt onset of various neuropsychological symptoms. she was a housewife with low socioeconomic level. her relatives mentioned that she had suffered from chronic constipation that did not respond to the common medicine. therefore, following the recommendation of a friend, she had made a mixture of 50 grams of grinded aspand, water and sugar. two hours after taking the cocktail, the symptoms were manifested as blurred vision, phonophobia, floating feeling, tinnitus ringing, and repetitive moving backward or forward. family history for psychiatric disorders was negative. she had controlled hypertension from some years ago treated with atenolol tablet 100 mg/per day. on admission, she was lethargic and also disoriented to person, time and place. the patient had mild tachycardia (heart rate: 105/minute) and increased blood pressure (blood pressure: 160/90 mmhg) with oral temperature of 37.8 ◦c. physical examination of the head, neck, chest, abdomen, and extremities did not show any positive finding. the neurological examination revealed somnolence, p copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 107 emergency (2016); 4 (2): 106-107 depersonalization, derealization, poor concentration, and ataxia. blood glucose level, blood gas analysis, biochemistry profile, and brain imaging were reported as normal. 12 leads electrocardiography revealed normal sinus tachycardia. since the patient history was reliable, harmala intoxication was the definite diagnosis. she was treated with intravenous fluid of dextrose/saline, metoclopramide and antacid. after 12 hours of conservative management, signs and symptoms of toxicity were relieved and she left the hospital in a stable condition. outpatient follow-up revealed full recovery with no complication. discussion: aspand intoxication usually is transient and self-limited and improves with supportive therapy. but consuming a high dose of it accidentally, intentionally, or for suicidal attempt may cause mortality. aspand intoxication can cause various symptoms like misperception, impairment in sensorium and cognition, mild hyperthermia, or on the contrary, autonomic dysfunction like bradycardia and hypotension (7, 12). the symptomatology is dominated as neurological, gastrointestinal, and cardiovascular, respectively . in a study by mahmoudian et al., tremor and seizure without increased spinal reflex, respiratory paralysis, hypothermia, and central nervous system suppression were reported as main manifestations of the mentioned intoxication (2). yet, our patient had tremor and increase in deep tendon reflexes. it is suggested that this herb can imitate a monoamine oxidase inhibitor effect (6). the manifestations are dose dependent and higher dosage may increase probability of poisoning. drug substance and metal poisoning can have the same presentation (4, 13). since there is no specific anti-dote for this type of poisoning, the standard treatment is control of vital signs and supportive therapy. there are dissociative, psychotic and anxiety states that need special symptomatic treatment. conclusion: aspand may be used for various purposes, but ingestion can be so dangerous and life threatening. it imitates psychiatric and neurological presentation and can cause morbidity and mortality especially in higher doses. acknowledgment we acknowledge all the staff of internal medicine service and emergency unit of shahid beheshti hospital of taft for handling this patient. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. rezvan sadr mohammadi and reza bidaki wrote the manuscript, fazlollah mirdrikvand revised a part of it, nader mostafavi and reza bidaki designed it, reza bidaki and pouria yazdian revised and submitted it. references: 1. bahmani m, rafieian-kopaei m, parsaei p, mohsenzadegan a. the anti-leech effect of peganum harmala l. extract and some anti-parasite drugs on limnatis nilotica. afr j microbiol res. 2012;6(10):2586-90. 2. mahmoudian m, jalipour h, dardashti ps. toxicity of peganum harmala: review and a case report. iranian journal of pharmacology & therapeutics. 2002;1(1):1-4. 3. moloudizargari m, mikaili p, aghajanshakeri s, asghari mh, shayegh j. pharmacological and therapeutic effects of peganum harmala and its main alkaloids. pharmacogn rev. 2013;7(14):199. 4. berdai ma, labib s, harandou m. peganum harmala l. intoxication in a pregnant woman. case reports in emergency medicine. 2014;2014. 5. aqel m, hadidi m. direct relaxant effect of peganum harmala seed extract on smooth muscles of rabbit and guinea pig. pharm biol. 1991;29(3):176-82. 6. shi c-c, chen s-y, wang g-j, liao j-f, chen c-f. vasorelaxant effect of harman. eur j pharmacol. 2000;390(3):319-25. 7. aarons dh, victor rossi g, orzechowski rf. cardiovascular actions of three harmala alkaloids: harmine, harmaline, and harmalol. j pharm sci. 1977;66(9):1244-8. 8. rhalem n, khattabi a, soulaymani a, ouammi l, soulaymani-bencheikh r. etude rétrospective des intoxications par les plantes au maroc: expérience du centre anti poison et de pharmacovigilance du maroc (1980-2008). toxicologie maroc. 2010;5:5-8. 9. casey r. 298 alleged anti-fertility plants of india. 1960. 10. saha j, savini e, kasinathan s. ecbolic properties of indian medicinal plants. 1961. 11. boulos l. medicinal plants of north africa. medicinal plants of north africa. 1983. 12. abdel-fattah a, matsumoto k, murakami y, el-hady k, mohamed m, watanabe h. inhibitory effects of harmaline on the tryptophan induced 5-hvdroxyt syndrome and body temperature changes in pargyline-pretreated rats. jpn j pharmacol. 1996;27:39-47. 13. achour s, rhalem n, khattabi a, et al. [peganum harmala l. poisoning in morocco: about 200 cases]. therapie. 2011;67(1):53-8. archives of academic emergency medicine. 2023; 11(1): e9 rev i ew art i c l e serum glial fibrillary acidic protein in detecting intracranial injuries following minor head trauma; a systematic review and meta-analysis sajjad ahmadi1, shayan roshdi dizaji2, asrin babahajian3, mohammadreza alizadeh2, arash sarveazad4,5∗, mahmoud yousefifard2,6 † 1. emergency medicine research team, faculty of medicine, tabriz university of medical sciences, tabriz, iran. 2. physiology research center, iran university of medical sciences, tehran, iran. 3. liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 4. colorectal research center, iran university of medical sciences, tehran, iran. 5. nursing care research center, iran university of medical sciences, tehran, iran. 6. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: developing novel diagnostic and screening tools for exploring intracranial injuries following minor head trauma is a necessity. this study aimed to evaluate the diagnostic value of serum glial fibrillary acidic protein (gfap) in detecting intracranial injuries following minor head trauma. methods: an extensive search was performed in medline, embase, scopus, and web of science databases up to the end of april 2022. human observational studies were chosen, regardless of sex and ethnicity of their participants. pediatrics studies, report of diagnostic value of gfap combined with other biomarkers (without reporting the gfap alone), articles including patients with all trauma severity, defining minor head trauma without intracranial lesions as the outcome of the study, not reporting sensitivity/specificity or any other values essential for computation of true positive, true negative, false positive and false-negative, being performed in the prehospital setting, assessing the prognostic value of gfap, duplicated reports, preclinical studies, retracted articles, and review papers were excluded. the result was provided as pooled sensitivity, specificity, diagnostic score and diagnostic odds ratio, and area under the summary receiver operating characteristic (sroc) curve with a 95% confidence interval (95% ci). results: eventually, 11 related articles were introduced into the meta-analysis. the pooled analysis implies that the area under the sroc curve for serum gfap level in minor traumatic brain injuries (tbi) was 0.75 (95% ci: 0.71 to 0.78). sensitivity and specificity of this biomarker in below 100 pg/ml cut-off were 0.83 (95% ci: 0.78 to 0.89) and 0.39 (95% ci: 0.24 to 0.53), respectively. the diagnostic score and diagnostic odds ratio of gfap in detection of minor tbi were 1.13 (95% ci: 0.53 to 1.74) and 3.11 (95% ci: 1.69 to 5.72), respectively. the level of evidence for the presented results were moderate. conclusion: the present study’s findings demonstrate that serum gfap can detect intracranial lesions in mild tbi patients. the optimum cut-off of gfap in detection of tbi was below 100 pg/ml. as a result, implementing serum gfap may be beneficial in mild tbi diagnosis for preventing unnecessary computed tomography (ct) scans and their related side effects. keywords: brain injuries, traumatic; diagnosis; biomarkers cite this article as: ahmadi s, roshdi dizaji s, babahajian a, alizadeh m, sarveazad a, yousefifard m. serum glial fibrillary acidic protein in detecting intracranial injuries following minor head trauma; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e9. https://doi.org/10.22037/aaem.v11i1.1682. ∗corresponding author: arash sarveazad; colorectal research center, rasoul-e-akram hospital, nyaiesh ave., tehran, iran; tel/fax: +982166554790; email: arashsarveazad@gmail.com, orcid: https://orcid.org/0000-00019273-1940. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index s. ahmadi et al. 2 1. introduction traumatic brain injury (tbi) is the leading cause of death and debilitation among the young population worldwide (1). statistics demonstrate its worldwide prevalence at 8.4%, which has been considered a major health concern in developing countries. the incidence rate and disability-adjusted life years (daly) of tbi increased significantly from 1990 to 2016. tbi is a significant burden on the healthcare system and constitutes a large portion of hospital visits and admissions (2). based on clinical assessments, and typically, the glasgow coma scale (gcs), tbi patients are commonly classified into three subgroups: mild (gcs:13-15), moderate (gcs:9-12), and severe (gcs:8-12), with mild tbi accounting for more than 85% of cases (3, 4). the intracranial lesions caused by tbi are conventionally detected using imaging techniques, in particular, non-contrastenhanced computed tomography (ct) scan and rarely, magnetic resonance imaging (mri) (5, 6). however, the role of imaging techniques has been debated due to negative findings in a vast majority of mtbi patients and the considerable amount of hazardous ionizing radiation associated with it and cost implications imposed by it (7). according to available data, only 16% of mild tbi patients have demonstrable intracranial lesions on computed tomography (ct) imaging (8). to prevent unnecessary imaging, multiple clinical decision rules with varied diagnostic values have been developed to identify those who are at risk of having pathoanatomical intracolonial lesions (9). one limitation with current decision rules is the presence of clinical criteria, including headache, post-traumatic amnesia, nausea, vertigo, dizziness, and consciousness assessment that are self-reporting or non-specific and subject to clinical examiner bias. the demand for minimally invasive objective parameters in detecting brain injury has led to increasing attention toward serum biomarkers serving as supplementary screening tools. in light of advancements in understanding the molecular biology and pathways involved in neuronal damage, s100-b and neuron specific-enolase (nse), two brain-enriched cytoplasmic markers, were widely studied to aid in diagnosing central nervous system injuries (1, 10, 11). although demonstrated to pose promising efficacy in providing insight into injury severity and progression, these biomarkers are subject to some drawbacks. studies on multiple trauma have revealed that extracranial sources of nse and s100-b release confound its interpretation and impede its practical clinical † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; email: yousefifard.m@iums.ac.ir, orcid: https://orcid.org/0000-0001-5181-4985. utility in acute settings (12, 13). among emerging serum biomarkers, studies outlined glial fibrillary acidic protein (gfap) as a brain-specific astroglia cytoskeleton filament that is released into peripheral circulation upon neuronal injuries due to patency of the bloodbrain barrier (bbb) (14). clinical investigations have demonstrated that the gfap serum level has a high correlation with the lesion volume and severity in traumatic brain injuries. this made gfap a potential candidate for diagnostic and prognostic purposes in tbi evaluation. although the evidence has supported that gfap holds the potential to predict intracranial injuries in tbi patients, there is yet considerable heterogeneity among the available studies (9, 15, 16). given the inconsistencies found between studies and the lack of a consensus, this systematic review with meta-analysis has been carried out to draw a conclusion on the diagnostic utility of gfap in detecting intracranial lesions following mild tbi. 2. methods 2.1. study design the present study is a systematic review to investigate the diagnostic value of gfap in detecting traumatic intracranial lesions following tbi. an extensive search was performed in available electronic resources and databases to achieve this aim and discover all the relevant papers. the current study design adhered to moose guidelines (17). the pico description of the present study is shown below: the problem or population (p) consists of human studies performed on patients with mild tbi. mild tbi was defined as a gcs between 13 to 15. the index test (i) was the venous serum value of gfap. the comparison (c) was done with reference standards such as ct scans, mri, and standard guidelines for detecting sport-related concussions. the outcome (o) was intracranial lesions. we have not previously registered our study protocol in any registries. 2.2. search strategy the keywords were selected by reviewing the mesh and emtree terms for medline (via pubmed) and embase databases, respectively. other possibly related keywords were found by consulting the experts in the field and scrutinizing the jargon and related article titles and keywords. subsequently, using the appropriate combination of the keywords, the exploration was executed in medline, embase, scopus, and web of science databases from their inception to the end of april 2022. the detailed search queries on each database are presented in appendix 1. in addition, a manual search was done on the bibliography of related articles this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 3 archives of academic emergency medicine. 2023; 11(1): e9 and results obtained from google and google scholar motor search engines. 2.3. eligibility criteria diagnostic accuracy studies performed on the serum value of gfap in mild tbi patients were considered relevant. human studies on adult patients (age>15 years old) were chosen, regardless of participants’ sex and ethnicity. exclusion criteria included pediatrics studies, report of diagnostic value of gfap combined with other biomarkers (without reporting the gfap alone), no discrimination of tbi severity based on gcs, mild tbi without intracranial lesions as the outcome of the study, being performed in the prehospital setting, assessing the prognostic value of gfap, and preclinical studies. we also excluded duplicated reports, reports with inadequate data on sensitivity/specificity or any corresponding values essential for computation of true positive (tp), true negative (tn), false positive (fp), and false-negative (fn), retracted articles, and reviews. we applied no restrictions on the language, geographical location, or publication year during our survey. we also excluded studies assessing the biomarker of interest qualitatively. if the serial serum level of gfap was evaluated in a study, the first observation was included in the meta-analysis. 2.4. screening and data extraction records collected during systematic and manual searches were exported to endnote version 20.0 software (clarivate analytics, philadelphia, pa, usa), and duplicates were removed. two independent researchers screened the records by their titles and abstracts and determined those deemed as possibly related and retrieved the full text of relevant articles. any discordances were resolved by discussion or consulting the third researcher. eligible studies based on the abovementioned inclusion and exclusion criteria were included for data collection. we extracted the data on study information (design, first author name, study time and location, publication year), patients’ characteristics (sample size and demographics, level of consciousness based on gcs), outcome definition and standard reference, overall number and demographics of outcome and non-outcome groups, serum gfap assay method, the time elapsed from the traumatic accident until blood acquisition, recommended gfap cut-off points and associated sensitivity and specificity. whenever two or more articles were extracted from the same registry, the article with larger sample size or longer follow-up duration was selected to be included. additionally, if evaluated values were reported in distinct subgroups (e.g., age groups, sex groups, etc.), the data was documented and analyzed corresponding to that group. reviewers manually entered all the extracted data into a predefined checklist in an excel sheet (microsoft, redmond, washington, usa). 2.5. risk of bias assessment the methodological quality of included articles was assessed using the quality assessment of diagnostic accuracy studies version 2 (quadas-2) tool (18). this implementation involves risk of bias and applicability, which were evaluated and reported in each article by two independent researchers. quadas-2 instruction classifies scores into three levels: low risk, high risk, and unclear. any disagreements were addressed by discussion or consulting with the third researcher. 2.6. level of evidence two independent reviewers determined the level of evidence for our primary interest outcome using the grading of recommendations, assessment, development, and evaluations (grade) framework (19). the grade framework consists of subjective evaluation of five domains of risk of bias, imprecision, inconsistency, indirectness, and publication bias. 2.7. statistical analysis analyses were performed using stata 17.0 statistical software. the studies were summarized and sorted based on their diagnostic value. attaining the tp, tn, fp, and fn values was the priority in the data collection process. if the aforementioned data was not reported in the articles, the authors were contacted through email and asked to provide the required data. finally, in the case of the authors’ unresponsiveness, the data were extracted by employing analytics on reported sensitivity and specificity. analyses were performed using the "midas" package of stata, which pools article diagnostic value data using a bivariate mixed-effects binary regression modeling framework. the result was provided as pooled sensitivity, specificity, diagnostic score and diagnostic odds ratio, and area under the summary receiver operating characteristic curve (sroc) with a 95% confidence interval (95% ci). to measure the heterogeneity between studies, i2 statistics were performed. whenever heterogeneity (i2>50%) was found, subgroup analysis was carried out to investigate the source of heterogeneity. since three studies included a small portion of moderate tbi patients (1.0% to 3.6% of their total sample size), a sensitivity analysis was applied to studies that included only mild tbi patients. in addition, a sensitivity analysis was performed according to the definition of the non-tbi group and the setting of patients (mild-tbi vs. sport-related concussion). meta-analysis was performed when the required data were reported in at least four distinct analyses. publication bias was assessed using deek’s asymmetry funnel plot test. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index s. ahmadi et al. 4 3. results 3.1. screening and specificity of included papers the search in databases led to 4475 articles. after removing the duplicate items, abstracts of 2352 papers were screened. in the next step, full texts of 84 articles were obtained for a more thorough evaluation. eventually, 11 related articles (2030) were introduced into the meta-analysis. figure 1 represents the inclusion process and reasons for exclusions. the eventual eligible papers included 8 cohort studies, 2 clinical trials, and 1 cross-sectional study. all studies were conducted on suspected or confirmed tbi patients who attended the hospital. the control group was composed of ct-negative patients in 10 papers, and both ct-negative and healthy individuals in 1 study. these studies included 4978 individuals (907 tbi patients and 4071 non-tbi subjects). the average age of included patients was 24 to 56.0 years old. diagnosis of tbi was achieved employing ct scan or mri in all studies. in all studies, the time interval between head trauma and gfap measurement was less than 24 hours post-injury. eight studies investigated mild tbi (21-25, 27, 28, 30), and 3 explored mild to moderate injuries (20, 26, 29). it is worth mentioning that moderate tbi cases comprised a small portion of all participants (1-3.6% of the whole population), so the study was mainly performed on mild tbi cases. it must be noted that in the included studies, data were reported in various subgroups and different gfap cut-off points; therefore, data were formulated into 30 distinctive analyses in the current meta-analysis. table 1 depicts a summary of included studies’ characteristics. 3.2. risk of bias to investigate the risk of bias, the quadas-2 instrument was utilized. the risk of bias in all articles was categorized as low risk (table 2). in conclusion, the overall risk of bias score was low. 3.3. diagnostic value of gfap in detecting intracranial lesions in mild tbi the pooled analysis implies that the area under the sroc curve for gfap serum level in mild tbi is 0.75 (95% ci: 0.71 to 0.78) (figure 2). sensitivity and specificity of this biomarker were calculated as 0.83 (95% ci: 0.78 to 0.87) and 0.38 (95% ci: 0.27 to 0.59), respectively (figure 3). diagnostic score and diagnostic odds ratio of gfap in the detection of intracranial lesions in mild tbi were calculated to be 1.13 (95% ci: 0.53 to 1.74) and 3.11 (95% ci: 1.69 to 5.72), respectively (figure 4). 3.4. subgroup analysis subgroup analyses were performed in response to apparent heterogeneity among articles in analyses (i2 value between 91.55% and 100%). the findings of this analysis are presented in table 3. as was speculated, the type of the study had a profound impact on the findings. after performing separate analyses based on study type, the heterogeneity between studies decreased significantly and was figured to be 0.0%. over and above that, the value for gfap sensitivity in detection of intracranial lesions in mild tbi was evaluated as 0.62 (95% ci: 0.25, 1.00) for cross-sectional studies and 0.84 (95% ci: 0.79, 0.89) for cohorts, which can be concluded that crosssectional studies had the least reported value among other studies. another subgroup analysis was performed based on reported gfap cut-off points. the reported cut-off points varied from 3.0 to 848 pg/ml. as a result, they were grouped into three sets with values of less than 100 pg/ml, 100-300 pg/ml, and above 400 pg/ml. analyses revealed that another source of heterogeneity among studies was variability in cut-off points recommended by studies. grouping of analyses based on cut-off points led to a reduction in the heterogeneity to 0%. the sensitivity and specificity of gfap in cut-offs below 100 pg/ml were estimated to 0.83 (95% ci: 0.78 to 0.89) and 0.39 (95% ci: 0.24 to 0.53), respectively. additionally, the sensitivity and specificity of this biomarker in cut-offs between 100-300 pg/ml were 0.79 (95% ci: 0.67 to 0.90) and 0.32 (95% ci: 0.08 to 0.57), respectively. finally, in cut-offs above 400 pg/ml the sensitivity and specificity were measured as 0.89 (95% ci: 0.81 to 0.96) and 0.43 (95% ci: 0.15 to 0.71), respectively. seemingly, in cut-offs below 100 pg/ml and above 400 pg/ml, gfap has the optimum performance in detecting intracranial lesions among mild tbi patients. there were 17 vs. 5 analyses in the group with cut-offs below 100 pg/ml and above 400 pg/ml, respectively. as a result, a cut-off below 100 pg/ml seems to be associated with more reliable diagnostic accuracy for gfap in identifying intracranial lesions in mild tbi cases (table 3). 3.5. sensitivity analysis in addition to subgroup analysis, sensitivity analysis was performed in the current study. sensitivity analysis on studies in which the control group consisted of ct-negative patients revealed that the difference in the control group also does not influence sensitivity (sensitivity=0.84; p=0.16) and specificity (specificity=0.40; p=0.86) of gfap in diagnosis of intracranial lesions of mild tbi patients. on the contrary, sensitivity analysis indicated that the studies that exclusively recruited mild tbi cases have reported significantly lower sensitivity than studies on mild to moderate tbi patient populations (0.80 vs. 0.95; p<0.001). however, it has no effect on specificity of gfap (0.38 vs. 0.42; p=0.93) (table 4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 5 archives of academic emergency medicine. 2023; 11(1): e9 3.6. publication bias deek’s asymmetry funnel plot test was performed to assess publication bias. the analysis implied no possible publication bias in the included studies (p=0.97) (figure 5). 3.7. certainty of evidence there was high heterogeneity among included study, but our subgroup analysis could find the sources of heterogeneity. the overall grade was rated up one point due to large magnitude of effect size (based on diagnostic odds ratio). so, the level of evidence was graded moderate (table 4). 4. discussion our findings demonstrated that gfap serum level is capable of detecting intracranial lesions in mild tbi patients (auc:0.75 with 95% ci: 0.71 to 0.78). our pooled analysis indicated that gfap has a promising diagnostic value with 83% sensitivity and 39% specificity in cut-offs below 100 pg/ml. utilizing serum gfap measurement may aid healthcare providers in being more selective in imaging acquisition, while providing safe and efficient care in the emergency department and acute care settings. measuring serum gfap as a traumatic brain injury signature would lower the rate of unnecessary ionizing imaging and shorten the time spent for in-patient observation in the high-burden ed. based on our investigations, the proposed cut points for gfap among studies varied in a range of 3-848 pg/ml. as a result, we categorized these cut points into 3 groups with values of less than 100 pg/ml, 100-300 pg/ml, and above 400 pg/ml based on the fact that the increase in cut point results in lower sensitivity and higher specificity (31). the analyses indicated that the serum level of gfap has the optimum performance in cut-offs below 100 pg/ml and above 400 pg/ml. however, only 5 studies reported cut-offs above 400 pg/ml, compared to 17 studies on cut-offs below 100 pg/ml. therefore, we can only rely on findings of cut-offs below 100 pg/ml, and there is a need to investigate the optimum cut-offs in future studies. application of imaging for diagnosis of sport-related concussion is limited when considering the fact that athletes sustain multiple head traumas during their sport career. so, diagnosis of this type of mild tbi is based on clinical judgment of team physicians and recommended guidelines. meier et al. reported that gfap is not significantly elevated from baseline preinjury level following sport-related concussion in football players, except for athletes with loss of consciousness and amnesia (32). asken et al. concordantly showed moderate diagnostic accuracy of gfap (auc:0.67, 95%ci:0.57–0.78) for sport-related concussion and demonstrated superiority of s100b (auc:0.72, 95%cu:0.63–0.81) in this regard (33). it can be concluded that this biomarker holds moderate potential in detecting clinically diagnosed sports-related concussions. nevertheless, addition of objective brain biomarkers would be beneficial in diagnosis of concussion among athletes who have minimal or less severe self-reporting symptoms and thus, imposing a challenge for physicians. objective assessment of biomarkers can reduce the reliance on symptoms for diagnosis of concussion as some athletes may deliberately not report them to avoid being prohibited from participation in the competitions (32). also, the rise of biomarkers following concussion can represent the pathophysiological responses underlying the concussion and could provide prognostic information regarding the required time before clearance for full return to sport even when symptoms are alleviated. however, only 2 articles on the diagnostic accuracy of gfap in sport-related concussion were found in our search, and further investigations are suggested in this regard. the reference standard imaging in many studies was the ct scan, and this would affect the judgment of the sensitivity and specificity of gfap, as some forms of brain damage, such as micro-injuries and diffuse axonal injury (dai), are not conspicuously visible in ct scans and require more advanced neuroimaging modalities such as mri (34). moreover, in the current meta-analysis, there were 3 studies on mild to moderate tbi patients. however, there were 1%, 1.6%, and 3.6% of patients in the moderate tbi group. seemingly, a significant proportion of patients were in the mild tbi group; hence, including these studies in the pooled analysis is justifiable. we believe that akin to cardiac troponin for diagnosis of myocardial damage, a singular value of initial post-traumatic gfap may not be able to provide concise and valid information on the extent of the patient’s central nervous system (cns) damage. serial measurements of gfap could be more informative since its concentration pattern, and bulk release can shed light on the dynamics of brain injury evolution and identification of delayed injuries. additionally, the mere serum value of gfap is not capable of characterizing different types of brain lesions (i.e., skull fractures, subdural hematoma, contusion, sub-arachnoid hemorrhage, etc.) and development of a model consisting of a panel of blood biomarkers originating from multiple types of cells engaged in tbi is under investigation. in 2018, the food and drug administration (fda) approved the clinical application of a semiquantitative kit developed by banyan biomarkers, inc. for the measurement of gfap and uch-l1 to reduce the overuse of ct imaging in tbi (13). the concurrent measurement of uch-l1 and gfap enhanced their separate diagnostic values and 97.6% sensitivity and 37.4% specificity were reported when a combination assessment was performed (20). other studies evaluated the incorporation of inflammatory, endothelial, and neural damage markers to reach a more favorable diagnostic accuracy. however, this multiplex assessment is associated with higher costs compared to the ct scan this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index s. ahmadi et al. 6 and constrains health resources (24, 35). the value of integrating blood biomarkers into the existing clinical decision rules also deserves further research. kinetically, gfap rises immediately after tbi with a peak level reached during the first 24 hours following injury and declines to near normal value in the next 14 to 30 days postinjury (22, 36). although gfap persists in circulation for a long time, the majority of studies included in this review had a time interval of less than 24 hours between traumatic accident and blood draw; hence, it is speculated that the delayed measurement of gfap may yield different diagnostic value (4, 37). moreover, the primary laboratory technique for gfap assay was reported to be ellsa, which could take time for results to be prepared. further studies are required to endorse the clinical utility of gfap at bedside evaluation by introducing easy and rapid measurement techniques. it should be noted that the presented cut-offs and associated sensitivity and specificity cannot be adopted for pediatric tbi or birth-inflicted brain injuries, since we primarily focused on adults. additionally, caution should be implemented on the approach to gfap values in patients with neuropsychological or renal function impairment, as these two disease categories may impact the serum gfap concertation as a source of production and excretion, respectively. this brought up concerns about the reduced accuracy of gfap in the diagnosis of intracranial injuries among the geriatric population, who suffer a higher rate of comorbidities and, are significantly more prone to harbor traumatic lesions yet symptomatically silent on presentation. to overcome this challenge, gardner et al. recommended the integration of tau level measurement to improve the diagnostic accuracy of gfap in elder patients (38). finally, we didn’t aim to explore the cost-effectiveness of the proposed biomarker assessment, but it is worth stating that some studies reported controversial results on the costs of tbi biomarkers, and further studies in different contexts and healthcare systems are warranted to reach a common conclusion (38, 39). 5. conclusions the findings of the current review demonstrated that with a moderate level of evidence, gfap serum level is capable of detecting intracranial lesions in mild tbi patients and might facilitate the clinical decision-making and delivery of targeted therapeutic care. additionally, sensitivity and specificity of gfap in cut-offs below 100 pg/ml were measured to be 0.83 and 0.42, respectively. taken together, the measurement of gfap after injury may be beneficial in mild tbi diagnosis and prevents unnecessary ct scans if used as a complementary indicator to individual patient clinical characteristics and examinations. 6. declarations 6.1. acknowledgments not applicable. 6.2. ethics approval not applicable. 6.3. patient consent not applicable 6.4. informed consent not applicable. 6.5. availability of data and materials all data generated or analyzed during this study are included in this published article and its supplementary information file. 6.6. permission to reproduce material from other sources not applicable. 6.7. clinical trial registration not applicable. 6.8. conflicting interests the authors declare that they have no competing interests. 6.9. funding maragheh university of medical sciences supported this research. 6.10. author contributions ideation and design: my, and sa. data collection: my, sa, ab, as, srd. analysis: my, ma. interpretation of results: all authors. drafting the work: my, sa, ma. revising draft critically for important intellectual content: all authors. the authors read and approved the final manuscript. references 1. gutierre mu, telles jpm, welling lc, rabelo nn, teixeira mj, figueiredo eg. biomarkers for traumatic brain 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biomarkers for monitoring human traumatic brain injury dynamics: a systematic review. front neurol. 2017;8:300. 38. calcagnile o, anell a, undén j. the addition of s100b to guidelines for management of mild head injury is potentially cost saving. bmc neurol. 2016;16(1):200. 39. ruan s, noyes k, bazarian jj. the economic impact of s100b as a pre-head ct screening test on emergency department management of adult patients with mild traumatic brain injury. j neurotrauma. 2009;26(10):1655-64. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 9 archives of academic emergency medicine. 2023; 11(1): e9 table 1: summary characteristics of included studies author, year, country study type gcs1 sample size mean age (year) male (n) assay tbi criteria timing (hrs) tbi patients (n) non-tbi patients (n) cut-offs (pg/ml) bazarian, 2018, multiple countries trial 9 to 15 1780 49.9 1107 elisa ct <12 107 1673 22 cevik, 2019, turkey crosssectional 14 to 15 48 24 38 elisa ct <4 24 24 230 clarke, 2021, norway cohort 13 to 15 343 32.5 206 elisa ct and mri <24 76 267 57.5 gardner, 2018, usa cohort 13 to 15 169 41.88 127 elisa ct <24 56 113 430 lagerstedt, 2018, spain and switzerland cohort 15 241 48.7 to 52.4 96 and 67 elisa ct <6 38 203 97.3 okonkwo, 2020, usa trial 13 to 15 1137 40.12 435 elisa ct <24 358 779 13.1, 37.8, 113.3, 190.1 papa, 2012, usa cohort 9 to 15 117 38 elisa ct <4 32 85 35 papa, 2022, usa cohort 13 to 15 349 40 240 elisa ct <4 23 326 67 posti, 2019, finland cohort 13 to 15 93 56 37 elisa ct <24 37 56 66.62, 132, and 540 welch, 2016, multiple countries cohort 9 to 15 251 45.6 151 elisa ct 6 36 215 15 yue, 2019, usa cohort 13 to 15 450 36.3 285 elisa mri <24 120 330 4.4, 12.95, 25.15, 71.95, 282.7, and 848.75, 1data was presented as range. ct: computed tomography scan; elisa: enzyme-linked immunosorbent assay; gcs: glasgow coma scale; n: number; tbi: traumatic brain injury; mri: magnetic resonance imaging. table 2: risk of bias assessment of included studies based on quadas-2 tool study risk of bias applicability patients’ selection index test reference standard flow and timing patients’ selection index test reference standard overall bazarian, 2018 , , , , , , , , cevik, 2019 , , , , , , , , clarke, 2021 , , , , , , , , gardner, 2018 , , , , , , , , lagerstedt, 2018 , , , , , , , , okonkwo, 2020 , , , , , , , , papa, 2012 , , , , , , , , papa, 2022 , , , , , , , , posti, 2019 , , , , , , , , welch, 2016 , , , , , , , , yue, 2019 , , , , , , , , ,: low risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index s. ahmadi et al. 10 table 3: subgroup and sensitivity analyses for identification of source of heterogeneity among included studies parameter no. of analyses sensitivity p specificity p2 i2(%) study type cohort 21 0.84 [0.79, 0.89] 0.03 0.42 [0.29, 0.55] 0.16 0.0 cross-sectional 1 0.62 [0.25, 1.00] 0.14 0.39 [0.27, 0.50] 0.64 0.0 trial 5 0.83 [0.73, 0.92] 0.01 0.27 [0.06, 0.47] 0.65 0.0 gfap cut-offs (pg/ml) <100 17 0.83 [0.78, 0.89] <0.001 0.39 [0.24, 0.53] 0.60 0.0 100 to 300 5 0.79 [0.67, 0.90] <0.001 0.32 [0.08, 0.57] 0.94 0.0 >400 5 0.89 [0.81, 0.96] 0.12 0.43 [0.15, 0.71] 0.60 0.0 control group ct negative patients 25 0.84 [0.79, 0.89] 0.16 0.40 [0.28, 0.52] 0.86 0.0 healthy control 2 0.79 [0.61, 0.97] 0.15 0.22 [0.00, 0.52] 42 0.0 severity of tbi mild 24 0.80 [0.76, 0.84] <0.001 0.38 [0.25, 0.50] 0.93 82.0 moderate to mild 3 0.95 [0.92, 0.99] 0.95 0.42 [0.08, 0.77] 0.74 82.0 gfap: glial fibrillary acidic protein; ct: computed tomography scan; tbi: traumatic brain injuries. table 4: certainty of evidence based on grade framework outcome sample size diagnostic odds ratio risk of bias imprecision inconsistency (i2) indirectness publication bias judgment and level of evidence* intracranial lesion 4978 3.11 (95% ci: 1.69 to 5.72) not serious not present not present not present not present moderate: ⊕⊕⊕⊕⊕ rated up one point: • large magnitude of effect** *, based on our judgment **, based on diagnostic odds ratio figure 1: flow diagram of screening in current meta-analysis. gfap: glial fibrillary acidic protein; ct: computed tomography scan; mri: magnetic resonance imaging; tbi: traumatic brain injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 11 archives of academic emergency medicine. 2023; 11(1): e9 figure 2: summary receiver operating characteristics (sroc) of glial fibrillary acidic protein )gfap( in diagnosis of mild traumatic brain injuries. auc: area under the curve; sens: sensitivity; spec: specificity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index s. ahmadi et al. 12 figure 3: sensitivity and specificity of glial fibrillary acidic protein )gfap( in diagnosis of mild traumatic brain injuries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index 13 archives of academic emergency medicine. 2023; 11(1): e9 figure 4: diagnostic score and diagnostic odds ratio of glial fibrillary acidic protein )gfap( in diagnosis of mild traumatic brain injuries. figure 5: publication bias in assessment of diagnostic accuracy of glial fibrillary acidic protein )gfap( in detection of mild traumatic brain injuries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/tem/index introduction methods results discussion conclusions declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 55 emergency (2016); 4 (2): 55-64 review article comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis mahmoud yousefifard1, masoud baikpour2, parisa ghelichkhani3, hadi asady4, abolfazl darafarin5, mohammad reza amini esfahani5, mostafa hosseini6, 7*, mehdi yaseri6, saeed safari5 1. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. 2. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 3. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. department of occupational health engineering, faculty of public health, tehran university of medical sciences, tehran, iran. 5. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 6. sina trauma and surgery research center, tehran university medical sciences, tehran, iran. 7. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. *corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical scienc es, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127. received: june 2015; accepted: august 2015 abstract introduction: the potential benefit of ultrasonography for detection of thoracic bone fractures has been proven in various surveys but no comprehensive conclusion has been drawn yet; therefore, the present study aimed to conduct a thorough meta-analytic systematic review on this subject. methods: two reviewers independently carried out a comprehensive systematic search in medline, embase, isi web of knowledge, scopus, cochrane library, and proquest databases. data were summarized as true positive, false positive, true negative and false negative and were analyzed via stata 11.0 software using a mixed-effects binary regression model. sources of heterogeneity were further assessed through subgroup analysis. results: data on 1667 patients (807 subjects with and 860 cases without thoracic fractures), whose age ranged from 0 to 92 years, were extracted from 17 surveys. pooled sensitivity and specificity of ultrasonography in detection of thoracic bone fractures were 0.97 (95% ci: 0.90-0.99; i2= 88.88, p<0.001) and 0.94 (95% ci: 0.86-0.97; i2= 71.97, p<0.001), respectively. the same measures for chest radiography were found to be 0.77 (95% ci: 0.56-0.90; i2= 97.76, p<0.001) and 1.0 (95% ci: 0.91-1.00; i2= 97.24, p<0.001), respectively. the sensitivity of ultrasonography was higher in detection of rib fractures, compared to fractures of sternum or clavicle (97% vs. 91%). moreover, the sensitivity was found to be higher when the procedure was carried out by a radiologist in comparison to an emergency medicine specialist (96% vs. 90%). conclusion: base on the findings of the present meta-analysis, screening performance characteristic of ultrasonography in detection of thoracic bone fractures was found to be higher than radiography. however, these characteristics were more prominent in detection of rib fractures and in cases where was performed by a radiologist. key words: thoracic fractures; ultrasonography; radiography; diagnostic tests, routine cite this article as: yousefifard m, baikpour m, ghelichkhani p, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. emergency. 2016; 4(2):55-64. introduction: arly diagnosis of rib fractures can rapidly indicate the source of thoracic pain and be helpful in pain management of trauma patients. other than pain, rib fractures have been reported to be associated with morbidity and mortality in elderly patients (3-5). in most emergency departments, ultrasonography is considered as one of the most useful screening tools for rapid evaluation of trauma patients (6). application of ultrasonography for assessment of chest wall injuries has been reported from 1980s (7). since then the technology of ultrasound devices has significantly improved so that images with higher resolutions are obtained. in light of these improvements, the diagnostic value of this modality has been considerably enhanced (9). in this regard, studies have illustrated a considerably high diagnostic value of ultrasonography in detection of thoracic fractures, even higher than that of chest radiography (8, 10-12). for instance in his narrative review, chan referred to ultrasonography as a reliable diagnostic tool e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 56 for detection of thoracic bone fractures (13). nevertheless, still no comprehensive review has been carried out comparing the diagnostic values of chest ultrasonography and radiography in detection of thoracic fractures. one solution is to perform a meta-analysis on the available evidence (15, 16). accordingly, the present systematic review and meta-analysis aimed to determine the diagnostic values of chest ultrasonography and radiography in detection of thoracic bone fractures. methods: search strategy and selection criteria the study protocol was established based on the guidelines of meta-analysis of observational studies in epidemiology statement (moose) (19). after selection of keywords from medical subject heading (mesh) terms and emtree, two reviewers (m.y, p.g) independently carried out an extended systematic search in databases of medline (via pubmed), embase (via ovidsp), isi web of knowledge, scopus, cochrane library, and proquest without any time or language limitations. the keywords included “ultrasonography” or “sonography” or “ultrasound” or “radiography” or “chest film” or “chest radiograph” combined with “rib fractures” or “chest wall fracture” or “sternum fracture” or “sternal fracture” or “clavicle fracture” or “scapula fracture”. additionally, the bibliographies of original and review articles as well as google scholar were also searched. all the studies evaluating the diagnostic accuracy of ultrasonography or chest radiography in detection of chest wall fractures were assessed. review and editorial articles, case reports and studies with sample populations of less than 10 patients were excluded. data extraction two reviewers (m.y, p.g) independently worked on summarizing the data regarding assessing quality of studies, baseline characteristics of patients (age, gender, the number of patients with and without hemothorax, the etiology of hemothorax), the characteristics of ultrasonography device (transducer, frequency), physicians in charge of imaging interpretation, blinding status, sampling method (consecutive, convenience), study design figure 1: flowchart of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 57 emergency (2016); 4 (2): 55-64 t a b le 1 : c h a re ct e ri st ic s o f in cl u d e d s tu d ie s s tu d y n o . o f p a ti e n t (+ / ) a g e 1 ( y e a r s ) m a le ( % ) r e fe r e n c e / in d e x t r a n s d u c e r / o p e r a to r s a m p li n g / f r a c tu r e w e a k n e s s e s h e n d r ic h 1 9 9 5 ( 1 ) 1 5 / 3 0 4 5 ( 2 9 -6 1 ) 5 7 .8 c x r / u s 7 .5 m h z / r a d io lo g is t c o n v e n ie n ce / st e rn u m l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s e n g in 2 0 0 0 (2 ) 1 8 / 5 3 5 .4 ( 1 8 -7 5 ) 8 2 .6 c x r / u s 7 .5 m h z / r a d io lo g is t c o n v e n ie n ce / s te rn u m r e tr o sp e ct iv e d e si g n l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s h u r le y 2 0 0 4 (8 ) 1 5 / 5 3 1 ( 1 6 -5 5 ) 7 8 .6 c t / u s , c x r 1 2 .5 m h z / r a d io lo g is t c o n se cu ti v e / r ib l o w s a m p le s iz e r a in e r 2 0 0 4 (1 1 ) 7 6 / 1 2 5 1 ± 1 9 5 9 c t / u s , c x r 5 -t o 1 0 -m h z / r a d io lo g is t c o n v e n ie n ce / s te rn u m ji n 2 0 0 6 (1 0 ) 2 3 / 1 6 4 5 .2 ( 1 5 -8 2 ) 5 2 c t / u s , c x r 5 -t o 9 -m h z / r a d io lo g is t c o n v e n ie n ce / m u lt ip le l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s t r a u b 2 0 0 7 (1 4 ) 6 8 / 7 3 4 7 .2 ( 1 8 -8 9 ) 7 5 c t / c x r n a / r a d io lo g is t c o n v e n ie n ce / r ib r e tr o sp e ct iv e d e si g n p o ss ib il it y o f se le ct io n b ia s w o o tt o n g o r g e s 2 0 0 8 ( 1 7 ) 1 3 1 / 9 4 0 .2 ( 0 .1 -0 .5 ) 4 1 .7 c t / c x r n a / r a d io lo g is t c o n se cu ti v e / r ib r e tr o sp e ct iv e d e si g n p o ss ib il it y o f se le ct io n b ia s l o w s a m p le s iz e c r o s s 2 0 1 0 (1 8 ) 4 3 / 5 7 1 0 .7 ( 1 -1 7 ) 8 7 .3 c x r / u s 1 0 to 1 5 -m h z / e p c o n v e n ie n ce / c la v ic le p o ss ib il it y o f se le ct io n b ia s w e in b e r g 2 0 1 0 ( 2 0 ) 2 5 / 1 8 7 1 3 ( 3 -2 3 ) n r c t / u s 7 .5 to 1 0 -m h z / e p c o n v e n ie n ce / c la v ic le a n d r ib p o ss ib il it y o f se le ct io n b ia s y o u 2 0 1 0 (2 1 ) 2 4 / 1 2 4 3 ( 8 -7 3 ) 5 2 .8 c t / u s 7 -t o 1 2 -m h z / r a d io lo g is t c o n se cu ti v e / r ib l o w s a m p le s iz e s z u c s -f a r k a s 2 0 1 1 (2 2 ) 3 9 / 2 4 6 4 .4 ± 1 4 .7 7 3 c t / c x r n a / r a d io lo g is t c o n v e n ie n ce / r ib r e tr o sp e ct iv e d e si g n l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s y a z k a n 2 0 1 2 ( 2 3 ) 8 3 / 8 3 4 0 .8 ( 1 6 -9 2 ) 7 3 .5 c t / c x r n a / s u rg e o n c o n se cu ti v e / r ib r e tr o sp e ct iv e d e si g n b ła s iń s k a 2 0 1 3 ( 2 4 ) 3 4 / 2 6 n r n r c t / c x r n a / r a d io lo g is t c o n se cu ti v e / m u lt ip le l o w s a m p le s iz e c h a r d o li 2 0 1 3 ( 2 5 ) 5 1 / 1 4 9 3 7 .9 ( 1 6 9 0 ) 8 4 c t / c x r n a / e p c o n v e n ie n ce / r ib t h e i n te rp re ta ti o n o f th e c x r a n d c t w e re n o t in b li n d f a sh io n p o ss ib le s e le ct io n b ia s u z u n 2 0 1 3 (1 2 ) 9 2 / 8 2 8 ( 1 5 4 0 ) 7 3 c t / u s , c x r n r / r a d io lo g is t c o n se cu ti v e / r ib p o ss ib il it y o f re p o rt in g b ia s h o ff s te tt e r 2 0 1 4 ( 2 6 ) 1 5 / 2 4 6 1 ( 2 4 -8 7 ) 6 0 .7 c t / c x r n a / r a d io lo g is t c o n se cu ti v e / m u lt ip le r e tr o sp e ct iv e d e si g n l o w s a m p le s iz e p a r k 2 0 1 5 (2 7 ) 5 5 / 5 5 5 6 .2 ( 1 6 .9 ) 5 7 .4 c t / c x r n a / r a d io lo g is t c o n se cu ti v e / r ib l o w s a m p le s iz e 1 , ( + / ): n u m b e r o f p a ti e n t w it h f ra ct u re / n u m b e r o f p a ti e n t w it h o u t fr a ct u re ; 2 , n u m b e r a re p re se n te d a s m e a n ± s ta n d a rd d e v ia ti o n o r (r a n g e ). c t : c o m p u te d t o m o g ra p h y ; c x r : c h e st r a d io g ra p h y ; e p : e m e rg e n cy p h y si ci a n ; n a : n o t a p p li ca b le ; n r : n o t r e p o rt e d ; u s : u lt ra so n o g ra p h y . this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 58 (retrospective, prospective). finally the number of true positive (tp), true negative (tn), false positive (fp), and false negative (fn) cases were extracteded. disagreements were discussed with the third reviewer (m.h) and a solution was proposed. in cases of data inaccessibility, the corresponding authors of the articles were contacted. data presented as charts were extracted via the method proposed by sistrom and mergo (28). in cases where only the sensitivity and specificity were presented, reliable web-based programs were used to calculate the number of tp, tn, fp, and fn cases. quality assessment quality of the studies were assessed based on the guidelines of 14-item quality assessment of diagnostic accuracy studies (quadas2) tool (29). the quality assessment were performed based on following items: acceptable reference tests, accounting for indeterminate results, avoiding differential verification bias, disease progression bias, incorporation bias and verification bias, blind index test interpretation, blind interpretation of reference test, explained withdrawal, relevant clinical data available, and representative spectrum. a total grading of poor, fair, and good was attributed to each survey and only the fair and good studies were included in the meta-analysis. statistical analysis analysis was performed using stata 11.0 statistical software via midas module. to evaluate the screening performance characteristics of ultrasonography and radiography in detection of chest wall fractures, summary receiver operative curves (srocs) were drawn and pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio with 95% confidence interval (95% ci) were calculated. due the high heterogeneity between the included studies, mixed-effects binary regression model was used. heterogeneity was evaluated through calculations of i2 and χ2 tests and a p value of less than 0.1 together with an i2 greater than 50% were considered as positive heterogeneity (30). subgroup analysis was performed to identify the source of heterogeneity. deek’s asymmetry funnel plot was used to search for publication bias. in all the analyses, p value of less than 0.05 was considered as statistically significant. results: study characteristics 17 out of 3894 studies found in the comprehensive search were included in the systematic review and metaanalysis (1, 2, 8, 10-12, 14, 17, 18, 20-27). 5 studies had assessed the diagnostic accuracy of ultrasonography in detection of thoracic bone fractures (1, 2, 18, 20, 21), 8 diagnostic value of chest radiography (14, 17, 22-27), and 4 diagnostic values of ultrasonography and radiography simultaneously (8, 10-12). 1667 cases (807 with and 860 without fractures) were extracted from the 17 mentioned articles, whose age ranged from 0 to 92 years old. figure 1 shows the inclusion process of articles and table 1 summarizes the characteristics of included studies. no publication bias was observed (figure 2). meta-analysis the results of the analyses are presented as srocs and funnel plots in figures 3 to 5. the area under the curve of sroc for ultrasonography and radiography in detection of chest wall fractures were found to be 0.99 (95% ci: 0.97-0.99) and 0.97 (95% ci: 0.96-0.99), respectively (figure 3). pooled sensitivity and specificity of ultrasonography in detection of thoracic bone fractures were 0.97 (95% ci: 0.90-0.99; i2= 88.88, p<0.001) and 0.94 (95% ci: 0.86-0.97; i2= 71.97, p<0.001), respectively (figure 4-a). these characteristics for radiography were found to be 0.77 (95% ci: 0.56-0.90; i2= 97.76, p<0.001) and 1.0 (95% ci: 0.91-1.00; i2= 97.24, p<0.001), respectively (figure 5-a). in addition, pooled positive and negative likelihood ratios of ultrasonography were 16.26 (95% ci: 6.26-38.87; i2= 59.14, p<0.001) and 0.03 (95% ci: 0.01-0.11; i2= 86.76, p<0.001), respectively (figure 4-b), while these measures for radiography were reported to be 774.63 (95% ci: 7.0-8573.0; i2= 96.62, p<0.001) and 0.23 (95% ci: 0.11-0.48; i2= 96.94, p<0.001), respectively (figure 5-b). subgroup analysis there were significant heterogeneity between the articles (figure 4 and 5). subgroup analysis was performed to remove its effects and find its probable sources. table 2 presents the results of this analysis. specificity of ultrasonography in detection of thoracic bone fractures was directly correlated with frequency of transducer (90% vs. 95%). the sensitivity of this modality was found to be higher in detection of rib fractures rather than fractures of clavicle or sternum (97% vs. 91%). moreover it was found that the sensitivity would be higher if the procedure is performed by a radiologist (96%) compared to an emergency medicine specialist (90%). sample size was another source of heterogeneity. studies with sample sizes of greater than 100 patients reported higher diagnostic accuracies for ultrasonography in detection of thoracic bone fractures (97% vs. 91%). as can be seen in table 2, the most important factor affecting sensitivity of chest radiography is the interpreting physician. the sensitivity was found to be 66% when the radiogram was interpreted by an emergency medicine specialist while it was 80% when interpreted by a radiologist. furthermore, consecutive sampling method compared with convenience (80% vs. 73%) and sample size of more than 100 patients (82% vs. 73%) were also found to be sources of heterogeneity. discussion: base on the results of the present meta-analysis sensitivity of chest ultrasonography in detection of thoracic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 59 emergency (2016); 4 (2): 55-64 t a b le 2 : s u b g ro u p a n a ly si s o f d ia g n o st ic a cc u ra cy f o r ch e st r a d io g ra p h y a n d u lt ra so n o g ra p h y i n d e te ct io n o f th o ra ci c b o n e f ra ct u re s n o . o f s tu d ie s b iv a r ia te r a n d o m -e ff e c t m o d e l s e n s it iv it y ( 9 5 % c i) p s p e c if ic it y ( 9 5 % c i) p h e te r o g e n e it y , i 2 p * u lt r a s o n o g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 3 0 .9 8 ( 0 .9 5 -1 .0 0 ) 0 .0 1 0 .9 0 ( 0 .7 7 -1 .0 0 ) 0 .5 5 4 3 .0 % 0 .1 8 c o n v e n ie n c e 6 0 .9 5 ( 0 .9 0 -0 .9 9 ) 0 .9 1 ( 0 .8 6 -0 .9 6 ) o p e r a to r e m e rg e n cy p h y si ci a n 3 0 .9 0 ( 0 .8 1 -0 .9 8 ) < 0 .0 0 1 0 .9 0 ( 0 .8 3 -0 .9 7 ) 0 .0 9 2 1 .0 % 0 .2 8 o th e r p h y si ci a n 6 0 .9 6 ( 0 .9 3 -0 .9 9 ) 0 .9 1 ( 0 .8 4 -0 .9 8 ) s a m p le s iz e < 1 0 0 6 0 .9 1 ( 0 .8 4 -0 .9 7 ) 0 .0 1 0 .9 0 ( 0 .8 3 -0 .9 7 ) 0 .0 4 1 2 .0 % 0 .3 2 ≥ 1 0 0 3 0 .9 7 ( 0 .9 4 -1 .0 0 ) 0 .9 3 ( 0 .8 7 -0 .9 8 ) f r e q u e n c y o f tr a n s d u c e r 5 -1 0 m h z 6 0 .9 4 ( 0 .8 9 -0 .9 9 ) 0 .6 2 0 .9 0 ( 0 .8 5 -0 .9 5 ) 0 .0 3 0 .0 % 0 .5 1 1 0 -1 5 m h z 3 0 .9 5 ( 0 .8 8 -1 .0 0 ) 0 .9 5 ( 0 .8 9 -1 .0 0 ) t y p e o f fr a c tu r e r ib 4 0 .9 7 ( 0 .9 3 -1 .0 0 ) 0 .0 1 0 .8 9 ( 0 .8 3 -0 .9 6 ) 0 .0 1 4 5 .0 % 0 .1 6 s te rn u m / c la v ic le 5 0 .9 1 ( 0 .8 4 -0 .9 7 ) 0 .9 3 ( 0 .9 4 -0 .9 8 ) r a d io g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 7 0 .8 0 ( 0 .5 9 1 .0 0 ) 0 .7 0 1 .0 0 ( 1 .0 0 1 .0 0 ) 0 .9 9 0 .0 % 0 .7 0 c o n v e n ie n c e 5 0 .7 3 ( 0 .4 5 1 .0 0 ) 1 .0 0 ( 0 .9 8 1 .0 0 ) o p e r a to r e m e rg e n cy p h y si ci a n 3 0 .6 6 ( 0 .2 7 1 .0 0 ) 0 .5 3 1 .0 0 ( 1 .0 0 1 .0 0 ) 0 .9 9 0 .0 % 0 .7 8 o th e r p h y si ci a n 9 0 .8 0 ( 0 .6 3 0 .9 8 ) 1 .0 0 ( 1 .0 0 1 .0 0 ) s a m p le s iz e < 1 0 0 7 0 .7 3 ( 0 .4 9 0 .9 7 ) 0 .4 4 1 .0 0 ( 1 .0 0 1 .0 0 ) 0 .9 9 0 .0 % 0 .5 7 ≥ 1 0 0 5 0 .8 2 ( 0 .6 1 1 .0 0 ) 1 .0 0 ( 1 .0 0 1 .0 0 ) t y p e o f fr a c tu r e r ib 8 0 .7 7 ( 0 .5 7 0 .9 7 ) 0 .5 6 1 .0 0 ( 1 .0 0 1 .0 0 ) 0 .9 9 0 .0 % 0 .9 8 s te rn u m / c la v ic le 4 0 .7 7 ( 0 .4 8 1 .0 0 ) 1 .0 0 ( 1 .0 0 1 .0 0 ) *, p v a lu e < 0 .1 w a s co n si d e re d a s si g n if ic a n t fo r h e te ro g e n e it y ; c i: c o n fi d e n c e i n te rv a l. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 60 bone fractures following trauma was prominently higher than radiography (97% vs. 77%). yet, the specificity of radiography was found to be significantly higher than ultrasonography in this regard (100% vs. 94%). on this basis and according to calculated likelihood ratios, a negative result of ultrasonography in detection of thoracic fracture is more reliable than radiography (negative likelihood ratio=0.03), while a positive result of chest radiography is more reliable than ultrasonography (positive likelihood ratio=774.63). ultrasonography had a higher sensitivity in diagnosis of rib fractures rather than other chest wall bones, while the type of fracture had no effect on diagnostic value of radiography. this finding can be ascribed to the higher attention that physicians pay to rib fractures rather than other chest wall bones such as scapula and sternum. fractures are diagnosed via ultrasonography based on observation of cortical bone disruption. in cases of small fractures, detection of this sign in sonogram and distinguishing it from other findings is highly dependent on the skills of the operator. the role of operator’s skills in detection of injuries via ultrasonography was verified in the present study as well (31-34). ultrasonography by a radiologist has a higher sensitivity compared to emergency medicine specialist. the present study found that the specificity of this modality increased with frequencies of higher than 10mhz which might be due to the higher resolution obtained with higher frequencies (35), making it easier to detect the signs of fracture. some narrative review articles and qualitative systematic reviews are indicative of the potential benefit of ultrasonography in detection of chest wall fractures. in this regard, chan, in his systematic review conducted on studies indexed in medline, declares that ultrasonography has a higher sensitivity in detection of thoracic bone fractures compared to radiography (13). finding the diagnostic accuracy of ultrasonography to be two times the ability of radiography in fracture diagnosis, dietrich et al. also referred to ultrasonography as a useful diagnostic tool for detection of rib fractures (36). the results of the present meta-analysis were congruent with these findings. presence of considerable heterogeneity between the included articles and simultaneous inclusion of retrospective and prospective studies in the meta-analysis were major limitations of this study. subgroup analysis was performed to overcome the heterogeneity problem. conclusion: base on the findings of the present meta-analysis, screening performance characteristic of ultrasonography in detection of thoracic bone fractures was found to be higher than radiography. however, these characteristics were more prominent in detection of rib fractures and in cases where was performed by a radiologist. acknowledgments: none conflict of interest: none funding support: this research has been supported by tehran university of medical sciences & health services grant number: 9302-38-25618. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. hendrich c, finkewitz u, berner w. diagnostic value of ultrasonography and conventional radiography for the assessment of sternal fractures. injury. 1995;26(9):601-4. 2. engin g, yekeler e, güloǧlu r, acunaş b, acunaş g. us versus conventional radiography in the diagnosis of sternal fractures. 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ann intern med. 2011;155(8):529-36. 30. higgins jp, thompson sg, deeks jj, altman dg. measuring inconsistency in meta-analyses. bmj. 2003;327(7414):557. 31. abbasi s, farsi d, hafezimoghadam p, fathi m, zare ma. accuracy of emergency physician-performed ultrasound in detecting traumatic pneumothorax after a 2-h training course. eur j emerg med. 2013;20(3):173-7. 32. bui-mansfield lt, chen dc, o'brien sd. accuracy of ultrasound of musculoskeletal soft-tissue tumors. am j roentgenol. 2015;204(2):w218. 33. fine d, perring s, herbetko j, hacking c, fleming j, dewbury k. three-dimensional (3d) ultrasound imaging of the gallbladder and dilated biliary tree: reconstruction from realtime b-scans. br j radiol. 1991;64(767):1056-7. 34. lee jh, jeong yk, park kb, park jk, jeong ak, hwang jc. operator-dependent techniques for graded compression sonography to detect the appendix and diagnose acute appendicitis. am j roentgenol. 2005;184(1):91-7. 35. majumdar s, kumar ps, pandit a. effect of liquid-phase properties on ultrasound intensity and cavitational activity. ultrason sonochem. 1998;5(3):113-8. 36. dietrich cf, mathis g, cui xw, ignee a, hocke m, hirche to. ultrasound of the pleurae and lungs. ultrasound med biol. 2015;41(2):351-65. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 62 a b figure 2: deeks’ funnel plot asymmetry test for assessment of publication bias. p values < 0.05 was considered as significant. ultrasonography (a); radiography (b). ess: effective sample sizes. a b figure 3: summary receiver operative curves (sroc) for ultrasound (a) and chest radiography (b) in detection of thoracic bone fractures. auc: area under the curve; sens: sensitivity; spec: specificity. 1 2 3 4 5 6 7 8 9 .1 .15 .2 .25 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.68 1 2 3 4 5 6 7 8 9 10 11 12 .05 .1 .15 .2 .25 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.39 12 3 4 5 6 7 8 9 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.97 [0.90 0.99] spec = 0.94 [0.86 0.97] sroc curve auc = 0.99 [0.97 0.99] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours 1 2 3 4 5 6 7 8 9 10 11 12 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.77 [0.56 0.90] spec = 1.00 [0.91 1.00] sroc curve auc = 0.97 [0.96 0.99] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 63 emergency (2016); 4 (2): 55-64 a b figure 4: forest plot of screening performance characteristics of chest ultrasonography in detection of thoracic bone fractures. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q = 71.95, df = 8.00, p = 0.00 i2 = 88.88 [82.99 94.77] 0.97[0.90 0.99] 1.00 [0.96 1.00] 1.00 [0.86 1.00] 0.93 [0.76 0.99] 0.95 [0.84 0.99] 1.00 [0.85 1.00] 0.80 [0.70 0.89] 0.93 [0.68 1.00] 0.89 [0.65 0.99] 1.00 [0.78 1.00]1.00 [0.78 1.00] author / year combined uzun 2013 you 2010 weinberg 2010 cross 2010 jin 2006 rainer 2004 hurley 2004 engin 2000 hendrich 1995 0.7 1.0 specificity (95% ci) q = 28.54, df = 8.00, p = 0.00 i2 = 71.97 [52.99 90.95] 0.94[0.86 0.97] 0.89 [0.52 1.00] 1.00 [0.74 1.00] 0.88 [0.80 0.94] 0.96 [0.88 1.00] 1.00 [0.79 1.00] 0.83 [0.52 0.98] 1.00 [0.48 1.00] 0.60 [0.15 0.95] 0.97 [0.83 1.00]0.97 [0.83 1.00] author / year combined uzun 2013 you 2010 weinberg 2010 cross 2010 jin 2006 rainer 2004 hurley 2004 engin 2000 hendrich 1995 0.1 1.0 dlr positive (95% ci) q = 32.43, df = 8.00, p = 0.00 i2 = 59.14 [59.14 91.52] 16.26[6.80 38.87] 6.63 [1.52 29.00] 25.48 [1.68 386.24] 7.89 [4.59 13.56] 27.17 [6.95 106.19] 33.29 [2.17 511.15] 4.82 [1.35 17.15] 10.88 [0.76 155.24] 2.22 [0.75 6.58] 20.02 [4.19 95.62]20.02 [4.19 95.62] author / year combined uzun 2013 you 2010 weinberg 2010 cross 2010 jin 2006 rainer 2004 hurley 2004 engin 2000 hendrich 1995 0.8 511.2 dlr negative (95% ci) q = 60.44, df = 8.00, p = 0.00 i2 = 86.76 [79.40 94.13] 0.03[0.01 0.11] 0.01 [0.01 0.10] 0.02 [0.01 0.32] 0.08 [0.02 0.31] 0.05 [0.01 0.19] 0.02 [0.01 0.33] 0.24 [0.14 0.40] 0.10 [0.02 0.48] 0.19 [0.04 0.82] 0.03 [0.01 0.50]0.03 [0.01 0.50] author / year combined uzun 2013 you 2010 weinberg 2010 cross 2010 jin 2006 rainer 2004 hurley 2004 engin 2000 hendrich 1995 0 1 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 64 a b figure 5: forest plot of screening performance characteristics of chest radiography in detection of thoracic bone fractures. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q =438.10, df = 11.00, p = 0.00 i2 = 97.49 [96.76 98.21] 0.77[0.56 0.90] 0.65 [0.61 0.68] 0.47 [0.21 0.73] 1.00 [0.96 1.00] 0.49 [0.35 0.63] 0.47 [0.30 0.65] 0.81 [0.71 0.89] 0.34 [0.28 0.41] 0.60 [0.51 0.69] 0.69 [0.57 0.80] 1.00 [0.85 1.00] 0.80 [0.70 0.89] 0.93 [0.68 1.00]0.93 [0.68 1.00] author / year combined park 2015 hoffstetter 2014 uzun 2013 chardoli 2013 blasinska 2013 yazkan 2012 szucs-farkas 2011 wootton 2008 traub 2007 jin 2006 rainer 2004 hurley 2004 0.2 1.0 specificity (95% ci) q =399.03, df = 11.00, p = 0.00 i2 = 97.24 [96.42 98.06] 1.00[0.91 1.00] 0.94 [0.90 0.96] 1.00 [0.86 1.00] 1.00 [0.63 1.00] 1.00 [0.98 1.00] 1.00 [0.87 1.00] 1.00 [0.96 1.00] 0.55 [0.38 0.71] 1.00 [0.96 1.00] 1.00 [0.96 1.00] 1.00 [0.79 1.00] 0.83 [0.52 0.98] 1.00 [0.48 1.00]1.00 [0.48 1.00] author / year combined park 2015 hoffstetter 2014 uzun 2013 chardoli 2013 blasinska 2013 yazkan 2012 szucs-farkas 2011 wootton 2008 traub 2007 jin 2006 rainer 2004 hurley 2004 0.4 1.0 dlr positive (95% ci) q =420.69, df = 11.00, p = 0.00 i2 = 96.62 [96.62 98.15] 774.63[7.00 85753.00] 10.50 [6.60 16.69] 23.44 [1.44 382.77] 17.90 [1.21 264.74] 147.12 [9.12 1000] 25.46 [1.60 405.59] 135.00 [8.50 1000] 0.76 [0.52 1.13] 114.43 [7.19 1000] 136.30 [8.55 1000] 33.29 [2.17 511.15] 4.82 [1.35 17.15] 10.88 [0.76 155.24]10.88 [0.76 155.24] author / year combined park 2015 hoffstetter 2014 uzun 2013 chardoli 2013 blasinska 2013 yazkan 2012 szucs-farkas 2011 wootton 2008 traub 2007 jin 2006 rainer 2004 hurley 2004 0.5 85753.0 dlr negative (95% ci) q =359.29, df = 11.00, p = 0.00 i2 = 96.94 [96.00 97.88] 0.23[0.11 0.48] 0.37 [0.34 0.42] 0.54 [0.34 0.86] 0.01 [0.01 0.09] 0.51 [0.39 0.67] 0.54 [0.39 0.74] 0.20 [0.13 0.30] 1.19 [0.89 1.00] 0.40 [0.32 0.49] 0.31 [0.22 0.44] 0.02 [0.01 0.33] 0.24 [0.14 0.40] 0.10 [0.02 0.48]0.10 [0.02 0.48] author / year combined park 2015 hoffstetter 2014 uzun 2013 chardoli 2013 blasinska 2013 yazkan 2012 szucs-farkas 2011 wootton 2008 traub 2007 jin 2006 rainer 2004 hurley 2004 0 1 archives of academic emergency medicine. 2023; 11(1): e56 or i g i n a l re s e a rc h effects of pre-hospital dexamethasone administration on outcomes of patients with copd and asthma exacerbation; a cross-sectional study thongpitak huabbangyang1, agasak silakoon1∗, chunlanee sangketchon1, jareeda sukhuntee1, jukkit kumkong2, tanut srithanayuchet2, parinya chamnanpol2, theeraphat meechai2 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. received: june 2023; accepted: july 2023; published online: 12 august 2023 abstract: introduction: chronic obstructive pulmonary disease (copd) and asthma exacerbation are two common emergency situations. this study aimed to investigate the impact of pre-hospital dexamethasone initiation on treatment outcomes of these patients. methods: in this retrospective cross-sectional and comparative study, data from the emergency medical service (ems) care report of patients with a final diagnosis of asthma or copd, coded with thailand’s emergency medical triage protocol, collected between january 1, 2021, and october 31, 2022, were used. data on baseline characteristics, emergency department length of stay (ed-los), and hospital admission rates were collected from electronic medical records and compared between cases with and without pre-hospital dexamethasone administration by ems. results: 200 patients with copd (n = 93) and asthma (n = 107) exacerbation were enrolled. the dexamethasone-treated group had a lower but statistically non-significant hospital admission rate (71.0% versus 81.0%, absolute difference: 10%, 95% confidence interval (ci): 21.76, 1.76; p = 0.100). in patients with asthma, the dexamethasone-treated had lower median ed-los time (235 (iqr: 165.5–349.5) versus 322 (iqr: 238–404) minutes; p = 0.003). dexamethasone-treated asthma patients had lower but statistically non-significant hospital admission rates (60.4% versus 78.0%, absolute difference: 17.55%, 95% ci: 34.96, 0.14; p = 0.510). in copd patients the dexamethasone-treated and untreated groups had non-significantly lower hospital admission rates (80.8% versus 85.40%, absolute difference: 4.60%, 95% ci: 19.82, 10.63; p = 0.561) and non-significantly lower ed-los (232 (iqr: 150 – 346) versus 296 (iqr: 212 – 330) minutes, absolute difference: 59 (130.81, 12.81); p = 0.106). conclusion: the dexamethasone administration by ems in pre-hospital setting for management of asthma and copd patients is beneficial in reducing the ed-los and need for hospital admission but its effects are not statistically significant, except regarding the ed-los of asthma exacerbation cases. keywords: asthma; pulmonary disease, chronic obstructive; dexamethasone; emergency medical services; length of stay cite this article as: huabbangyang t, silakoon a, sangketchon c, sukhuntee j, et al. effects of pre-hospital dexamethasone administration on outcomes of patients with copd and asthma exacerbation; a cross-sectional study. arch acad emerg med. 2023; 11(1): e56. https://doi.org/10.22037/aaem.v11i1.2037. 1. introduction chronic respiratory diseases are defined by the world health organization as diseases that affect the respiratory tract and other pulmonary structures and have acute exacerbations. aside from smoking, other risk factors include air pollution, occupational chemicals and dust, and incurable infections ∗corresponding author: agasak silakoon; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok 10400, thailand. tel: +66 2-244-3000, email: agasak@nmu.ac.th, orcid: https://orcid.org/0000-0002-7817-7944. (1). the most common types of chronic respiratory diseases seen in the emergency department (ed) include asthma and chronic obstructive pulmonary disease (copd). in the united states of america alone, approximately 4 million patients visit the ed each year due to asthma and copd, which reduce health-related quality of life and significantly increase mortality risk (2). according to an australian study, asthma and copd were found to be associated with an increased mortality rate, and one million patients died from asthma or copd exacerbations while being frequently served by emergency medical services (emss) (3), which were able to initiate diagnosis and treatment at the scene (4). in patients with acute copd exacerbations who called on ems, prompt treatthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 2 ment by the advanced life support (als) team influenced the ed length of stay (ed-los) and the hospital admission rate (5). according to standard treatment guidelines, the treatment of patients with asthma and copd in the context of ems differed in each area. in hospitals, corticosteroids are used to treat patients with asthma and copd, and their benefits have been widely accepted (6). since the main pathophysiologic mechanisms are airway inflammation in asthma (7) and mucus hypersecretion, airflow obstruction and hyperinflation, and an abnormal inflammatory response in the lungs in copd (8), corticosteroids are the medications of choice for these disorders (9, 10). early corticosteroid administration would help reduce the need for hospitalization and improve outcomes (5). a systematic review found that initiating corticosteroids within one hour of arrival at the ed was associated with a lower need for hospitalization (11). corticosteroids are natural hormones secreted from the adrenal cortex that have anti-inflammatory, metabolic, and immunological effects (3). in thai ems, dexamethasone was used as an alternative to treat patients with acute asthma and copd exacerbations (12). the present study aimed to evaluate the outcomes of initiating dexamethasone injection in pre-hospital setting on ed-los and hospital admission rates in patients with asthma and copd. 2. methods 2.1. study design and settings the retrospective cross-sectional comparative study was conducted at the vajira emergency medical service (v-ems) unit, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. of nine ems areas in bangkok, v-ems was the leader of ems unit zone area 1, dispatched from erawan center, bangkok, networking with a total of six public and private hospitals in the entire responsible area, which was 50 square kilometers and included 500,000 people (13, 14). in patient-managing operations, the ems team of v-ems in the area included at least three staff members who were paramedics or emergency nurse practitioners (enps) as operation team leaders and emergency medical technicians for each operation. in each operation, paramedics, or enps followed offline, and online medical protocols as directed by emergency physicians. in the study area, there were standard prehospital patient management guidelines endorsed by the national institute for emergency medicine for patients with asthma and copd (12). these guidelines allowed paramedics or enps to diagnose copd or asthma exacerbations based on pertinent symptoms, wheezing lung sounds, shortness of breath, poor air entry, and underlying copd, or asthma. they also allowed for the evaluation of initial management, including airway, breathing, and circulation, and the monitoring of vital signs, oxygen saturation, and end-tidal co2, as well as the administration of salbutamol or ipratropium bromide (berodual) via nebulization or a metered dose inhaler (mdi) with a spacer. furthermore, they allowed immediate intravenous (iv ) administration one dose of 8 mg iv dexamethasone at the scene. if patients did not respond to treatments and their symptoms worsened, a prehospital intubation was considered under the online medical protocol. in this study, we compared the outcomes of copd and asthma cases with and without pre-hospital administration of dexamethasone by ems between january 1, 2021, and october 31, 2022. 2.2. ethical statement this study was conducted in accordance with the tenets of the helsinki declaration of 1975 and its revisions in 2000. it was approved by the institutional review board of the faculty of medicine, vajira hospital, navamindradhiraj university (coa no. 006/2566). the informed consent requirement was waived because of the retrospective nature of the study and anonymity of all patient data. 2.3. participants data of patients with acute copd and asthma exacerbations were collected from ems patient care reports. adult patients over the age of 18 with a final diagnosis of acute copd or asthma exacerbations, symptom group 5 red 1 – 5 red 9, treated by v-ems, and transported to the ed, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand, were eligible to participate. patients who refused treatment or transportation to the hospital, were unable to provide medical history by themselves or had no relatives to provide previous medical history, had incomplete or missing data, or were receiving end-of-life, or palliative care were excluded from this study. 2.4. data collection the data were collected from the ems patient care report, which was a standard form used for recording the data of advanced ems operations in the bangkok ems (erawan center) and the bangkok advanced emergency operation unit. this form included data on ems operation units, patients, vital signs, and all ems treatments as recorded by dispatchers and paramedics, or enps, at the scene. these data were part of the remuneration for ems operation units. all data were filled in microsoft excel, including patients’ general characteristics (gender, age, prehospital diagnosis, comorbidities, treatment period, smoking history, bronchodilator use prior to ems arrival, and history of severe exacerbation), patients’ prehospital parameters (systolic blood pressure [sbp], diastolic blood pressure [dbp], heart rate [hr], respiratory rate [rr], temperature, pulse oximetry, wheezthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e56 ing, prehospital intubation, fluid resuscitation, bronchodilator type, bronchodilator dose, and bronchodilator administration method), patients’ ed parameters (sbp, dbp, hr, rr, temperature, pulse oximetry, wheezing, intubation, bronchodilator), and patient disposition (ed-los time in minutes and hospital admission). all data were reviewed by a principal investigator from the vajira hospital’s electronic medical records (emrs). 2.5. outcome measures the primary outcome was ed-los, while the secondary outcome was hospital admission rate. 2.6. definitions thailand’s emergency medical triage protocol and criteriabased dispatch code were severity codes derived from data on prehospital situation evaluation and patients’ symptoms at the scene. it includes 26 symptom groups. ed-los was defined as the time between patient arrival and discharge from the ed, whereas hospital admission rate was defined as rate of hospitalization following ed treatment (15). comorbidities are coexistent diseases in patients with copd and asthma. the data were collected from history taking from patients or patients’ relatives. history of severe exacerbation is having a history of emergency department visit by themselves or being transported by emergency medical service with acute asthma and copd exacerbations before the emergency call. 2.7. statistical analysis the sample size in the present study was estimated using sample size estimation from g power version 3.1.9.4, with an alpha confidence level of 0.05 and a power of 90%. the allocation ratio was 1 and the effect size (d) was 0.5 (medium) (16) because there have been no studies referring to the statistical data used to calculate the effect size. thus, the calculated sample size from the program was at least 86 per group, and after 10% of the sample size was added, the sample size was at least 96. therefore, in the present study, the sample size of patients with acute copd and asthma exacerbation was 200 in total, where the ems had administered dexamethasone for 100 and 100 had not received dexamethasone at the scene. continuous variables were presented as means and standard deviations, or medians and interquartile ranges (iqrs), while categorical variables were presented as frequencies and proportions. the two groups were compared using the independent t-test or mann-whitney u test for numeric variables and the chi-squared test or fisher’s exact test for categorical variables. ed-los and vital sign changes were compared between dexamethasone-treated and untreated groups using the independent t-test or mann-whitney u test, as appropriate, and were analyzed using multivariable logistic regression analysis. hospital admission rates were compared between dexamethasone-treated and untreated groups using the chi-squared test or fisher’s exact test, as appropriate, and were analyzed using the multivariable logistic regression analysis and median regression model. ibm statistical package for the social sciences software (ibm spss statistics for windows, version 26.0; armonk, ny, usa: ibm corp.) was used for statistical analysis. all statistical tests were considered statistically significant if the p-value was less than 0.05. 3. results 3.1. patients’ baseline characteristics 200 patients with copd (n = 93) and asthma (n = 107) exacerbation were enrolled. table 1 compares the baseline characteristics of patients between cases with and without prehospital dexamethasone administration. copd cases copd cases treated with dexamethasone (n = 52) in prehospital setting had lower mean ages (p = 0.016), higher male/female ratio (p = 0.035), higher comorbidity (p = 0.006), higher smoking history (p = 0.001), higher mean sbp (p = 0.002), higher mean dbp (p = 0.003), higher mean heart rate (p = 0.024), higher wheezing frequency (p < 0.001), and received more than one dose of the bronchodilator (p = 0.043). asthma cases in patients with asthma exacerbation, the dexamethasonetreated group had higher male to female ratio (p = 0.034), higher rate of received a bronchodilator prior to ems arrival (p = 0.004), higher mean sbp (p < 0.001), higher mean dbp (p < 0.001), lower mean temperature (p = 0.046), lower median pulse oximetry (p = 0.015), higher wheezing frequency (p < 0.001), higher median bronchodilator dose received (p < 0.001), and lower bronchodilator administration via a nebulizer (p < 0.001). 3.2. patient outcomes table 2 compares the ed-los and need for hospital admission between cases with and without prehospital dexamethasone administration by ems. overall, the dexamethasonetreated group had a lower but statistically non-significant hospital admission rate (71.0% versus 81.0%, absolute difference: 10%, 95% ci: 21.76, 1.76; p = 0.100) and significantly lower ed-los (235 versus 313.5 minutes; absolute difference: 77%, 95% ci: 118.55, 35.45; p = 0.100). in patients with asthma, the dexamethasone-treated had lower median ed-los time (235 (iqr: 165.5–349.5) versus 322 (iqr: 238–404) minutes; p = 0.003). dexamethasonethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 4 table 1: comparing the baseline characteristics of patients with chronic obstructive pulmonary disease (copd) and asthma exacerbation between cases with and without prehospital dexamethasone administration variables copd (n = 93) asthma (n = 107) treated (n = 52) untreated (n = 41) p-value treated (n = 48) untreated (n = 59) p-value gender male 44 (84.6) 27 (65.9) 0.035 31 (64.6) 26 (44.1) 0.034 female 8 (15.4) 14 (34.1) 17 (35.4) 33 (55.9) age (years) mean ± sd 69.79 ± 11.79 75.73 ± 11.35 0.016 68.67 ± 14.30 70.73 ± 15.74 0.484 comorbidities no 0 (0.0) 6 (14.6) 0.006 10 (20.8) 7 (11.9) 0.207 yes 52 (100) 35 (85.4) 38 (79.2) 52 (88.1) treatment period from 8 a.m. to 4 p.m. 18 (34.6) 16 (39.0) 0.760 18 (37.5) 20 (33.9) 0.920 from 4 to 12 p.m. 19 (36.5) 12 (29.3) 18 (37.5) 24 (40.7) from 12 p.m. to 8 a.m. 15 (28.8) 13 (31.7) 12 (25.0) 15 (25.4) smoking history no 10 (19.2) 21 (51.2) 0.001 35 (72.9) 49 (83.1) 0.204 yes 42 (80.8) 20 (48.8) 13 (27.1) 10 (16.9) bronchodilator use prior to ems arrival no 21 (40.4) 21 (51.2) 0.279 20 (41.7) 41 (69.5) 0.004 yes 31 (59.6) 20 (48.8) 28 (58.3) 18 (30.5) history of severe exacerbation no 39 (75.0) 30 (73.2) 0.841 30 (62.5) 42 (71.2) 0.341 yes 13 (25.0) 11 (26.8) 18 (37.5) 17 (28.8) vital signs at ed sbp (mmhg) 153.46 ± 31.17 133.39 ± 27.42 0.002 161.10 ± 30.97 128.58 ± 30.28 <0.001 dbp (mmhg) 90.33 ± 25.05 77.27 ± 16.74 0.003 94.58 ± 23.69 75.36 ± 21.68 <0.00 hr (bpm) 115.88 ± 23.82 104.44± 23.99 0.024 112.48 ± 18.96 109.78 ± 24.63 0.534 temperature (°c) 37.05 ± 0.48 37.15 ± 0.61 0.383 36.96 ± 0.57 37.23 ± 0.79 0.046 rr (bpm) 31.98 ± 5.70 30.15 ± 7.20 0.173 32.42 ± 4.59 30.58 ± 6.66 0.095 pulse oximetry median (iqr) 94 (90–96) 93 (88–96) 0.352 92 (88–94) 94 (90–97) 0.015 > 94% 24 (46.2) 15 (36.6) 0.353 10 (20.8) 28 (47.5) 0.004 <94% 28 (53.8) 26 (63.4) 38 (79.2) 31 (52.5) wheezing no 10 (19.2) 26 (63.4) <0.001 10 (20.8) 48 (81.4) <0.001 yes 42 (80.8) 15 (36.6) 38 (79.2) 11 (18.6) intubation in the prehospital setting no 46 (88.5) 39 (95.1) 0.459 48 (100.0) 55 (93.2) 0.126 yes 6 (11.5) 2 (4.9) 0 (0.0) 4 (6.8) fluid resuscitation no 20 (38.5) 24 (58.5) 0.054 22 (45.8) 19 (32.2) 0.149 yes 32 (61.5) 17 (41.5) 26 (54.2) 40 (67.8) bronchodilator type berodual 50 (96.2) 37 (90.2) 0.400 42 (87.5) 51 (86.4) 0.872 salbutamol 2 (3.8) 4 (9.8) 6 (12.5) 8 (13.6) bronchodilator dosage (dose) median (iqr) 2 (1–2.5) 1 (1–2) 0.101 2 (1–3) 1 (1–1) <0.001 1 dose 22 (42.3) 26 (63.4) 0.043 15 (31.3) 47 (79.7) <0.001 > 1 dose 30 (57.7) 15 (36.6) 33 (68.8) 12 (20.3) bronchodilator administration method nebulizer 36 (69.2) 30 (73.2) 0.678 30 (62.5) 54 (91.5) <0.001 mdi 16 (30.8) 11 (26.8) 18 (37.5) 5 (8.5) data are presented as numbers (%), means ± standard deviations, or medians (interquartile ranges). sbp: systolic blood pressure; dbp: diastolic blood pressure; hr: heart rate; rr: respiratory rate; mdi: metered dose inhaler; sd: standard deviation; ems: emergency medical service; iqr: interquartile range; ed: emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e56 table 2: comparing the emergency department length of stay and need for hospital admission between asthma and copd cases with and without prehospital dexamethasone administration outcomes treated untreated absolute difference (95% ci) effect estimate (95% ci) p-value copd (n = 93) ed-los (minutes) 232 (150 – 346) 296 (212 – 330) 59 (130.81, 12.81) 0.106 hospital admission 42 (80.8) 35 (85.4) 4.6 (19.82, 10.63) 0.72 (0.24–2.18) 0.561 asthma (n = 107) ed-los (minutes) 235 (165.5 – 249.5) 322 (238 – 404) 85 (139.53, 30.47) 0.003 hospital admission 29 (60.4) 46 (78.0) 17.55 (34.96, 0.14) 0.43 (0.19–1.00) 0.510 total ed-los (minutes) 235 (158–324.5) 313.5 (222–375) 77 (118.55, 35.45) 0.003 hospital admission 71 (71.0) 81 (81.0) 10.00 (21.76, 1.76) 0.57(0.30–1.11) 0.510 data are presented as numbers (%) or medians (interquartile ranges). ed-los: emergency department length of stay; ci: confidence interval; copd: chronic obstructive pulmonary disease. treated asthma patients had lower but statistically nonsignificant hospital admission rates (60.4% versus 78.0%, absolute difference: 17.55%, 95% ci: 34.96, 0.14; p = 0.510). in copd patients the dexamethasone-treated and untreated groups had non-significantly lower hospital admission rates (80.8% versus 85.40%, absolute difference: 4.60%, 95% ci: 19.82, 10.63; p = 0.561) and non-significantly lower ed-los (232 (iqr: 150 – 346) versus 296 (iqr: 212 – 330) minutes, absolute difference: 59 (130.81, 12.81); p = 0.106). 4. discussion dexamethasone administration by ems in pre-hospital setting for management of asthma and copd patients is beneficial in reducing the ed-los and need for hospital admission but its effects are not statistically significant, except regarding the ed-los of asthma exacerbation cases. the present study found that immediate initiation of iv dexamethasone administration by ems at the scene could reduce ed-los only in patients with asthma. patients with asthma exacerbations who received iv dexamethasone had a significantly shorter median ed-los time than those who did not. these findings were consistent with a previous study finding that patients receiving corticosteroid injections, such as dexamethasone, or hydrocortisone, in the ed had a lower risk of hospitalization and exacerbation recurrence (17, 18). in patients with asthma, copd, and anaphylaxis, offline protocols in some areas, such as australia (3), thailand (12), and florida (19), allowed ems personnel to initiate iv administration of systemic corticosteroids, such as dexamethasone, methylprednisolone, or prednisolone. however, there have been limited studies on the initiation of iv systemic corticosteroids in the ed for patients with asthma exacerbations, as recommended by the latest global initiative for asthma (gina) update 2023, because the anti-inflammatory effect can relieve the symptoms more quickly and reduce the risk of exacerbation recurrence (20). a previous study demonstrated that patients with asthma who received iv dexamethasone had a lower risk of disease exacerbation after ed discharge and a lower ed-los time (21). similarly, a systematic review and meta-analysis reported that children under the age of 18 years with asthma exacerbations, who received a two-dose regimen of dexamethasone in the ed had a shorter ed-los time, less symptom persistence, a lower risk of return visits or hospital readmissions, and a higher quality of life. these findings suggested that dexamethasone be administered immediately in the ed (22). however, studies on the outcomes of initiating corticosteroids, such as dexamethasone, by ems in patients with asthma exacerbations are scarce. a study on ems found that administering corticosteroids as part of the ems protocol was not associated with vital sign changes or ed-los time in pediatric patients with asthma. protocols in the area allowed only iv methylprednisolone administration, which was usually reserved for patients with severe asthma (19). the ems protocol in the study area allowed paramedics or enps to use iv dexamethasone (8 mg) as an alternative for adult patients with asthma and copd exacerbations at the scene. although no benefit was found for systemic use of corticosteroids in the present study, thai ems used dexamethasone in patients with copd exacerbations to decrease ed-los time. despite this, the global initiative for chronic obstructive lung disease (gold) (the 2020 gold science committee report) supports the initiation of systemic corticosteroids in the acute phase or in the ed, and corticosteroids are regularly used in clinical practice for the management of copd exacerbations, as previously recommended (23). a previous randomized clinical trial compared the efficacy of methylprednisolone with that of dexamethasone in management of copd exacerbations and found no significant difference in terms of ed-los time. patients receiving dexamethasone had better dyspnea control (p = 0.02), but the group receiving methylprednisolone had better cough control (p = 0.035). there was no significant difference between the two this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 6 drugs in terms of side effects on the 7th and 14th days. furthermore, the authors suggested that physicians should consider the most prominent symptoms of copd patients under treatment when selecting each type of corticosteroid (24). the present study was consistent with a previous study in a thai province that compared patients with copd exacerbations in the ed and found that patients receiving iv dexamethasone had no difference in terms of ed-los time (25). a narrative review reported that both shortand long-term corticosteroid use had relatively high side effects, including new or aggravated diabetes, hypertension, fractures, particularly in the elderly, venous thrombosis, sepsis, and gastrointestinal hemorrhage. accordingly, corticosteroid administration should be reduced, particularly in patients with copd exacerbations (26). the use of corticosteroids, such as dexamethasone, in patients with copd exacerbations may not be beneficial in the prehospital setting in terms of reduced edlos time. furthermore, drug administration should be initiated on a case-by-case basis and with the permission of the local ems protocol in each area. in the present study, initiating prehospital iv dexamethasone administration by ems in patients with asthma and copd exacerbations had no beneficial effect on hospital admission rates. this was consistent with a previous ed study that reported a significantly lower rate of hospitalization in pediatric patients with mild and moderate asthma who received corticosteroids (27). in addition, a previous study in the ambulance setting on pediatric patients aged 2–18 years with asthma exacerbations found that hospital admission rates were significantly lower in those who received corticosteroids by paramedics than in those who did not. besides, initiating prehospital corticosteroid administration by ems has been suggested to reduce hospital expenses for treating patients with acute asthma (26). furthermore, a previous study comparing the administration of iv methylprednisolone (125 mg) by ems to iv methylprednisolone in the ed found that initiating methylprednisolone administration by ems helped decrease hospital admission rates in patients with moderate to severe asthma (28). according to the present standard recommendations of global initiative for asthma (gina) update 2023, iv systemic corticosteroid administration should be initiated immediately in patients with asthma exacerbations because it could reduce hospital and intensive care unit admission rates (20). in patients with copd exacerbations, the present study reported a reduced risk of hospitalization with iv dexamethasone administration by ems. this was in contrast with a previous study demonstrating that patients with copd exacerbations at the ed receiving iv dexamethasone did not reduce overall hospital and intensive care unit admission rates (25), which may be due to the fact that patients with copd and asthma exacerbations serviced by ems mostly have severe symptoms. according to the present study, the incidence of prehospital intubation in patients with copd was 16.4%, while it was only 6.8% in patients with asthma. in addition, no asthmatic patients receiving iv dexamethasone administered by ems required prehospital intubation. furthermore, in patients with copd, and asthma, vital signs, such as rr, oxygen saturation levels, hr, and wheezing, did not differ between groups that received and did not receive iv dexamethasone administered by ems. this is because all of these patients were treated with a bronchodilator, salbutamol, or ipratropium bromide + fenoterol (berodual) via nebulizer or mdi with a spacer before initiating dexamethasone administration, as well as a relatively delayed dexamethasone effect that would take an hour (29), resulting in no clear difference in prehospital and ed vital signs. 5. limitations this study has some limitations. first, the present study was a retrospective single-center study that used two data sources: the ems patient care report and the emr database, which could introduce a selection bias. second, there may be unmeasured confounding factors associated with ed-los times and hospital admission rates, such as emergency room triage severity, patient overcrowding at the ed, the order of medical investigation, the order of additional laboratory tests, and so on, that influenced the outcomes. third, patients in this study were only transported to the vajra hospital’s ed. patients delivered to other hospitals’ eds should be collected because the level of the hospital ed may potentially affect ed-los times and hospital admission rates. fourth, in the present study, there was no classification of severity level of patients with asthma attacks and copd exacerbations (classified as mild, moderate, and severe) due to the retrospective nature of this observational study. paramedics or enps did not record the data regarding severity level in prehospital patient record. fifth, there was no data collection about receiving systemic corticosteroid before acute exacerbation, which was believed to affect results of the study. sixth, for copd patients in dexamethasone group, there was higher prevalence of smoking history and also significantly lower age in dexamethasone group. these were believed to affect the results of the study and may cause bias. finally, since not all patients, or relatives could provide a clear medical history, it was difficult for paramedics or enps to distinguish between asthma and copd in the prehospital setting, particularly, in patients without treatment history or new patients. hence, the final diagnosis in the hospital was chosen as the criterion for differentiating these two diseases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e56 6. conclusion dexamethasone administration by ems in pre-hospital setting for management of asthma and copd patients is beneficial in reducing the ed-los and need for hospital admission but its effects are not statistically significant, except regarding the ed-los of asthma exacerbation cases. 7. declarations 7.1. acknowledgments the authors are grateful to the navamindradhiraj university research fund for pub. we would like to thank the paramedics at v-ems, faculty of medicine vajira hospital, navamindradhiraj university, for facilitating in data collection and access in the present study, gawin tiyawat, md., chief of department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, and chunlanee sangketchon, md., deputy dean of faculty of science and health technology, navamindradhiraj university, for support and suggestions in the research development and aniwat berpan, md. for suggestions on english for the present study. 7.2. conflict of interest the authors have no conflicting interests to declare. 7.3. funding and support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution conceptualization: thongpitak huabbangyang, jukkit kumkong, tanut srithanayuchet, parinya chamnanpol and theeraphat meechai; methodology: thongpitak huabbangyang and agasak silakoon; software: thongpitak huabbangyang; validation: thongpitak huabbangyang; agasak silakoon and jareeda sukhuntee; formal analysis: thongpitak huabbangyang; investigation: thongpitak huabbangyang, jukkit kumkong, tanut srithanayuchet, parinya chamnanpol and theeraphat meechai; resources: thongpitak huabbangyang, jukkit kumkong, tanut srithanayuchet, parinya chamnanpol and theeraphat meechai; data curation: thongpitak huabbangyang; writing – original draft: thongpitak huabbangyang; writing review editing: thongpitak huabbangyang and agasak silakoon; visualization: thongpitak huabbangyang and jareeda sukhuntee; supervision: thongpitak huabbangyang and chunlanee sangketchon; project administration: thongpitak huabbangyang; funding acquisition: thongpitak huabbangyang. all authors read and approved the final version of manuscript. 7.5. data availability not applicable. 7.6. using artificial intelligence chatbots none. references 1. who. chronic respiratory 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exacerbation in the emergency department, chiangrai prachanukroh hospital. cmj. 2022;13(3):117-31 [thai]. 26. fishe jn, hendry p, brailsford j, salloum rg, vogel b, finlay e, et al. early administration of steroids in the ambulance setting: protocol for a type i hybrid effectivenessimplementation trial with a stepped wedge design. contemp clin trials. 2020;97:106141. 27. tyler a, cotter jm, moss a, topoz i, dempsey a, reese j, et al. outcomes for pediatric asthmatic inpatients after implementation of an emergency department dexamethasone treatment protocol. hosp pediatr. 2019;9(2):92-9. 28. knapp b, wood c. the prehospital administration of intravenous methylprednisolone lowers hospital admission rates for moderate to severe asthma. prehosp emerg care. 2003;7(4):423-6. 29. moore sg. intravenous dexamethasone as an analgesic: a literature review. aana j. 2018;86(6):488-93. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e68 ca s e re p o rt hamman’s syndrome accompanied by diabetic ketoacidosis; a case report koya yamashita1, takashi hongo1, tsuyoshi nojima1, tetsuya yumoto1∗, atsunori nakao1, hiromichi naito1 1. department of emergency, critical care, and disaster medicine, okayama university graduate school of medicine, dentistry, and pharmaceutical sciences, okayama, japan. received: june 2022; accepted: july 2022; published online: 21 august 2022 abstract: hamman’s syndrome is an uncommon clinical entity characterized by an idiopathic spontaneous pneumomediastinum as a result of a sudden increase in intra-alveolar pressure. it can be triggered by repeated vomiting or kussmaul breathing associated with diabetic ketoacidosis (dka). careful attention to this particular condition is needed to avoid under-diagnosis and to provide optimal management. herein, we report a case of an 18-yearold man complaining of chest discomfort and progressive weight loss, ultimately diagnosed with hamman’s syndrome secondary to dka. the patient’s symptoms disappeared after intravenous fluid and insulin administration, while his pneumomediastinum resolved following conservative treatment. our report highlights the importance of recognition of the links between pneumomediastinum as a cause of chest pain in patients with dka. keywords: hamman’s syndrome; diabetic ketoacidosis; mediastinal emphysema cite this article as: yamashita k, hongo t, nojima t, yumoto t, nakao a, naito h. hamman’s syndrome accompanied by diabetic ketoacidosis; a case report. arch acad emerg med. 2022; 10(1): e68. https://doi.org/10.22037/aaem.v10i1.1709. 1. introduction hamman’s syndrome, a spontaneous pneumomediastinum and pneumopericardium, accompanied by diabetic ketoacidosis (dka), is a rare clinical entity (1). although the pathogenesis of hamman’s syndrome caused by dka is multifactorial, intra-alveolar pressure can be increased by kussmaul breathing or repeated vomiting, which may lead to alveolar rupture (2,3). the vulnerability of alveolar walls due to malnutrition may influence the development of pneumomediastinum (3). lack of knowledge about hamman’s syndrome secondary to dka may lead to underdiagnose or unnecessary workups and surgical treatment (3,4). herein, we report an 18-year-old man who was diagnosed with hamman’s syndrome accompanied by dka. we share our experience and a literature review on etiology and pathogenesis to increase familiarity with this syndrome among physicians. physicians should be aware of the possibility that pneumomediastinum ∗corresponding author: tetsuya yumoto; department of emergency, critical care, and disaster medicine, okayama university graduate school of medicine, dentistry, and pharmaceutical sciences, 2-5-1 shikata-cho, kita-ku, okayama 700-8588, japan. phone: +81-86-235-7426, fax: +81-86-235-7427, e-mail: tyumoto@cc.okayama-u.ac.jp, orcid: https://orcid.org/0000-00031766-8026. can be induced by dka associated with type i diabetes mellitus. 2. case presentation an 18-year-old man, a college student with no medical history, came to the emergency department with two days of chest discomfort and history of marked body weight loss of 10 kg in two months. he did not take sugar-sweetened soft drinks daily. the patient reported polyuria and general fatigue for one week prior to admission. his height and weight were 165.0 cm and 63.9 kg, respectively. the patients’ vital signs were as follows: blood pressure 153/104 mmhg, heart rate 121 beats/minute, and respiratory rate of 26 breaths/minute. he had no cold sweating, no pallor, and no cyanosis. on physical examination, his chest was clear on auscultation with normal heart sound, and without chest wall tenderness on his abdomen. subcutaneous emphysema was not observed. he was severely dehydrated with poor skin turgor and marked delay in capillary refill >2s. significant laboratory results included a blood ph of 7.055, a blood glucose level of 901 mg/dl, white blood cells (wbc) 20,320 cells/µl, hemoglobin 16.2 g/dl, hemoglobin a1c 18%, serum potassium level of 6.1 mmol/l, blood urea nitrogen 20.6 mg/dl, and serum creatinine 0.93 mg/dl, antithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. yamashita et al. 2 insulin, anti-islet antigen-2, and antiglutamic acid decarboxylase antibody tests were negative. ketone bodies in his serum and urine were strongly positive. the other laboratory test results were unremarkable. chest x-ray revealed pneumomediastinum and supraclavicular subcutaneous emphysema without pneumothorax. a chest computed tomography (ct) revealed a few air bubbles inpneumomediastinum without pneumothorax or esophageal rupture (figure 1a). no abnormal findings were noted in in the trachea, bronchi, or lung parenchyma. the patient was diagnosed with dka associated with type i diabetes mellitus and pneumomediastinum. it was not known that our patient was diabetic until dka and pneumomediastinum were found. the patient was admitted to the intensive care unit for glycemic control, and hydration with normal saline and an intravenous regular insulin infusion were initiated. intravenous insulin was transitioned to a subcutaneous insulin regimen within 24 hours of initiation due to improvement of glycemic control and the recalcitrant acidosis. we arranged a consultation with a diabetologist to review and control the disease. the pneumomediastinum was treated conservatively. his chest discomfort disappeared and chest x-ray showed no signs of worsening amount of gas in the neck and mediastinum on day 2 of hospitalization. following resolution of dka, ct scan showed that the pneumomediastinum had disappeared on day 12 of hospitalization (figure 1b). he was discharged from the hospital on day 13 with an appointment for diabetic follow-up, including a chest radiograph. since his discharge from hospital, he has not experienced a recurrence of pneumomediastinum during the one-month follow-up, having fully recovered with adequate education regarding the management of insulin at home. 3. discussion the average age of hamman’s syndrome patients with dka is 20 years old. the average time period since diagnosis of diabetes mellitus is 7.2 years with average blood glucose levels of 638 mg/dl on presentation (2). pneumomediastinum is rare and happens when air leaks into the connective tissue and finally enters the mediastinal space into the chest cavity from the bowel, airways, or lungs. it can result from physical trauma or other events including mechanical ventilation, esophageal perforation, hyperemesis, dental extraction, and obstetric delivery. these conditions sometimes become very severe and fatal. although rare, pneumomediastinum accompanied by dka is a benign, self-limiting condition (2). in general, patients with pneumomediastinum usually figure 1: chest computed tomography (ct) scan on admission demonstrated pneumopericardium (white arrow) and pneumomediastinum (arrowhead) (a). ct showed that pneumomediastinum disappeared on day 12 of hospitalization (b). manifest extreme pain in the central chest. other symptoms include voice distortion, labored breathing, and subcutaneous emphysema, specifically affecting the chest, neck, and face. however, most of the clinical signs of pneumomediastinum complicated with dka are likely to have subsided by the time metabolic control has been achieved (2). since the symptoms of pneumomediastinum caused by esophageal rupture are similar to those of dka with pneumomediastinum, the exclusion of esophageal rupture, which has a high mortality rate, is the primary task in the diagnosis of dka complicated by pneumomediastinum (5). of note, perforation of the esophagus due to increased intraluminal pressures following violent vomiting is sometimes seen in dka (1,6). the precise pathophysiology of pneumomediastinum associated with dka remains to be explained. mainly, kussmaul breathing, the compensatory respiratory mechanism in metabolic acidosis, raises alveolar pressure, predisposing the alveoli to rupture. dka is often linked to severe vomiting caused by acidosis, which also increases intrathoracic pressures. gastroparesis accompanied by diabetic mellitus may exacerbate vomiting. our patient presented tachypnea, which may have been caused by increased expiratory efforts related to acidosis and ketotic hyperventilation. however, our patient did not complain of vomiting. hu et al. recently reported that fibrotic changes in the lungs of individuals with poorly-controlled diabetes predispose the alveoli to rupture at lower intrathoracic pressures (7). in addition, diabetic malnutrition may influence lung mechanics by increasing surface forces and decreasing tissue elasticity (8). a previous experimental study indicated that starvation resulted in decreased surface density of lamellar bodies and mitochondria in a rat model (8). although speculative, all this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e68 these phenomena might be involved in the development of hamman’s syndrome. of interest, there is a slight predominance of male patients with hamman’s syndrome (71%) due to men’s greater average muscle mass and their ability to create intrathoracic pressures higher than those of women (2). pneumomediastinum can be diagnosed based on chest radiography. chest ct is required to see mediastinitis or esophageal rupture. conservative management is required with follow-up. drainage of subcutaneous air or skin incisions may be needed in symptomatic patients with respiratory distress. gastroesophageal endoscopy is only indicated when other pathologies are being considered (6). in general, hamman’s syndrome is a benign entity with good prognosis. this case had several important points worth discussing. we reached an early diagnosis using non-invasive and inexpensive examinations by avoiding gastroesophageal endoscopy and/or surgical interventions. the clinical symptoms improved spontaneously after the intensive intravenous insulin therapies without invasive management. however, this disorder can have significant mortality if misdiagnosed or mistreated, which is almost 100% without insulin therapy (9). our report highlights the importance of recognition and management of pneumomediastinum induced by dka associated with type i diabetes mellitus. 4. conclusion emergency physicians should be aware of the possibility that pneumomediastinum can be induced by dka associated with type i diabetes mellitus. 5. declarations 5.1. acknowledgments none. 5.2. authors’ contributions all authors met the criteria for authorship based on the international committee of medical journal editors’ recommendations. 5.3. consent for publication written informed consent was obtained from the patient for the publication of this case report and the accompanying images. a copy of the consent form is available for review by the editor-in-chief of this journal. 5.4. funding and supports there is no funding to declare. 5.5. competing interests the authors declare that they have no competing interests. 5.6. data availability the data used and/or analyzed during the current study are available from the corresponding author upon reasonable request. references 1. alkhuja s, gazizov n, charles g. pneumomediastinum complicating diabetic ketoacidosis and boerhaave’s syndrome. case rep med. 2013;2013:598720. 2. pooyan p, puruckherr m, summers ja, byrd rp, roy tm. pneumomediastinum, pneumopericardium, and epidural pneumatosis in dka. journal of diabetes and its complications. 2004;18(4):242-7. 3. gill i, edhi ai, cappell ms. proposed characterization of the syndrome of epidural pneumatosis (pneumorrhachis) in patients with forceful vomiting from diabetic ketoacidosis as a clinico-radiologic pentad based on systematic literature review an illustrative case report. medicine (baltimore). 2020;99(35):e21001. 4. hayashi h, nagao n, yamazaki k, asai r, tanaka c, kawai m. spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip: a case report. int j surg case rep. 2021 mar;80:105691. 5. pain ar, pomroy j, benjamin a. hamman’s syndrome in diabetic ketoacidosis. endocrinol diabetes metab case rep. 2017;17-0135. 6. pauw rg, van der werf ts, van dullemen hm, dullaart rp. mediastinal emphysema complicating diabetic ketoacidosis: plea for conservative diagnostic approach. neth j med. 2007;65(10):368-71. 7. hu y, ma z, guo z, zhao f, wang y, cai l, et al. type 1 diabetes mellitus is an independent risk factor for pulmonary fibrosis. cell biochemistry and biophysics. 2014;70(2):1385-91. 8. sahebjami h, vassallo cl, wirman ja. lung mechanics and ultrastructure in prolonged starvation. am rev respir dis. 1978;117(1):77-83. 9. kitabchi ae, wall bm. diabetic ketoacidosis. med clin north am. 1995;79(1):9–37. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 1 emergency (2016); 4 (1): 1-10 review article screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis mahmoud yousefifard1, masoud baikpour2, parisa ghelichkhani3, hadi asady4, kavous shahsavari nia5, ali moghadas jafari6, mostafa hosseini7, 8*, saeed safari9 1. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. 2. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 3. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. department of occupational health engineering, faculty of public health, tehran university of medical sciences, tehran, iran. 5. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. 6. department of emergency medicine, bushehr university of medical sciences, bushehr, iran. 7. sina trauma and surgery research center, tehran university medical sciences, tehran, iran. 8. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 9. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical sciences , poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127. received: june 2015; accepted: august 2015 abstract introduction: the role of ultrasonography in detection of pleural effusion has long been a subject of interest but controversial results have been reported. accordingly, this study aims to conduct a systematic review of the available literature on diagnostic value of ultrasonography and radiography in detection of pleural effusion through a meta-analytic approach. methods: an extended search was done in databases of medline, embase, isi web of knowledge, scopus, cochrane library, and proquest. two reviewers independently extracted the data and assessed the quality of the articles. meta-analysis was performed using a mixed-effects binary regression model. finally, subgroup analysis was carried out in order to find the sources of heterogeneity between the included studies. results: 12 studies were included in this meta-analysis (1554 subjects, 58.6% male). pooled sensitivity of ultrasonography in detection of pleural effusion was 0.94 (95% ci: 0.88-0.97; i2= 84.23, p<0.001) and its pooled specificity was calculated to be 0.98 (95% ci: 0.92-1.0; i2= 88.65, p<0.001), while sensitivity and specificity of chest radiography were 0.51 (95% ci: 0.33-0.68; i2= 91.76, p<0.001) and 0.91 (95% ci: 0.68-0.98; i2= 92.86, p<0.001), respectively. sensitivity of ultrasonography was found to be higher when the procedure was carried out by an intensivist or a radiologist using 5-10 mhz transducers. conclusion: chest ultrasonography, as a screening tool, has a higher diagnostic accuracy in identification of plural effusion compared to radiography. the sensitivity of this imaging modality was found to be higher when performed by a radiologist or an intensivist and using 5-10mhz probes. key words: pleural effusion; ultrasonography; radiography; diagnostic tests, routine cite this article as: yousefifard m, baikpour m, ghelichkhani p, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. emergency. 2016;4(1):1-10. introduction: the role of ultrasonography in detection of pleural effusion was first discovered in the 1960s (1). one decade later the diagnostic value of a-mode ultrasonography in identification of pleural effusion was reported to be 95% (2). thus, the impression that ultrasonography is not a suitable modality for detection of chest lesions was rejected at that time. afterwards, various surveys were conducted evaluating the diagnostic accuracy of ultrasonography and radiography in identification of pleural effusion and most of them found a higher diagnostic value for ultrasonography compared to radiography (3-5). however, ultrasonography is still not considered as the first diagnostic tool for detection of pleural effusion and the majority of physicians use radiography for this propose (6). although a radiogram captured in lateral decubitus position with horizontal rays has a high sensitivity and specificity in detection of pleural effusion but it cannot be obtained from all the patients especially critically ill and trauma victims (4). other views of chest radiogram this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 2 have low sensitivities in this regard (7, 8). vast improvements of technology have led to development of handheld and pocket-size ultrasound devices (9, 10). a metaanalysis was performed in 2010 on four studies that reported the sensitivity and specificity of ultrasonography in detection of pleural effusion to be 93% and 96%, respectively (11). yet, inclusion of few surveys and lack of sensitivity analysis and publication bias confirm the necessity of an update on this subject. therefore, this study aims to conduct a systematic review of the available literature determining the diagnostic value of ultrasonography and radiography for detection of pleural effusion through a meta-analytic approach. methods: search strategy and selection criteria this study was designed according to the consensus statement of meta-analysis of observational studies in epidemiology (moose) (12). extended systematic search was carried out in databases of medline (via pubmed), embase (via ovidsp), isi web of knowledge, scopus, cochrane library, and proquest based on the keywords obtained from medical subject heading (mesh) terms and emtree. the keywords included “ultrasonography” or “sonography” or “ultrasound” or “chest film” or “chest radiograph” combined with “pleural effusion” or “effusion” or “pleural free fluid”. the directive was to find prospective and retrospective studies assessing the diagnostic value of ultrasonography or chest radiography in detection of pleural effusion. two of the authors (m.y, p.g) independently searched for sources and contacted the authors of relevant articles to figure 1: flowchart of the study. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 3 emergency (2016); 4 (1): 1-10 t a b le 1 : c h a re ct e ri st ic s o f in cl u d e d s tu d ie s s tu d y n o . o f p a ti e n t (+ / )1 a g e 2 (y e a r s ) m a le (% ) r e fe r e n c e / in d e x t r a n s d u c e r / o p e r a to r s a m p li n g w e a k n e s s e s m a 1 9 9 7 (5 ) 2 6 / 2 1 4 ≥ 1 8 n r c t / u s , c x r 3 .5 -t o 2 .5 -m h z / e p c o n se cu ti v e / t ra u m a r e tr o sp e ct iv e d e si g n k a ta o k a 2 0 0 0 ( 3 ) 6 0 / 2 2 7 6 .0 ± 1 2 .9 3 8 c t / u s , c x r 3 .5 m h z / in te rn is t c o n se cu ti v e / c ri ti ca ll y i ll l o w s a m p le s iz e o n ly e v a lu a ti n g o f c h f p a ti e n t l ic h te n s te in 2 0 0 4 ( 4 ) 1 0 0 / 2 8 4 5 8 ± 1 5 n r c t / u s , c x r 5 m h z / in te n si v is t c o n se cu ti v e / c ri ti ca ll y i ll r o c c o 2 0 0 8 ( 8 ) 3 8 / 1 4 2 4 2 ± 1 4 6 6 .7 c t / u s , c x r 3 .5 m h z / in te n si v is t c o n se cu ti v e / t ra u m a l o w s a m p le s iz e k it a z o n o 2 0 1 0 ( 7 ) 1 1 7 / 8 3 5 4 ( 1 4 -9 1 ) 6 0 c t / c x r n a / r a d io lo g is t c o n se cu ti v e / c ri ti ca ll y i ll r e tr o sp e ct iv e d e si g n z a n o b e tt i 2 0 1 1 ( 1 3 ) 2 5 / 1 1 7 3 ( 2 1 -1 0 1 ) 5 1 c t / u s , c x r 5 – t o 8 -m h z / e p c o n se cu ti v e / c ri ti ca ll y c t w a s p e rf o rm e d i n s o m e p a ti e n ts x ir o u c h a k i 2 0 1 1 ( 1 4 ) 6 3 / 2 1 5 7 .1 ± 2 1 .5 8 1 c t / u s , c x r 5 – t o 9 -m h z / in te n si v is t c o n v e n ie n c e / c ri ti ca ll y i ll l o w s a m p le s iz e s c h le d e r 2 0 1 2 ( 1 5 ) 3 5 / 1 3 n r n r o u tc o m e / u s , c x r 5 to 9 -m h z / r a d io lo g is t c o n se cu ti v e / c ri ti ca ll y i ll l o w s a m p le s iz e k a s r a e i 2 0 1 4 ( 1 6 ) 2 7 / 7 1 8 -7 0 5 3 .8 c t / u s , c x r 5 to 9 -m h z / r a d io lo g is t c o n se cu ti v e / c ri ti ca ll y i ll l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s p o c k e ts iz e u lt r a s o n o g r a p h y d a le n 2 0 1 5 ( 1 0 ) 3 9 / 8 5 7 4 ( 3 5 – 9 1 ) 5 2 h ig h -e n d u s / u s 1 .7 to 3 .8 -m h z / n u rs e c o n se cu ti v e / h e a rt f a il u re l o w s a m p le s iz e g r a v e n 2 0 1 5 ( 9 ) 9 5 / 2 3 6 7 ( 3 5 -8 6 ) 6 6 h ig h -e n d u s / u s , c x r 1 .7 to 3 .8 -m h z / n u rs e c o n v e n ie n c e / c a rd ia c su rg e ry l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s s to c k 2 0 1 5 (1 7 ) 2 1 / 7 6 8 ( 2 4 -9 4 ) 4 2 .8 h ig h -e n d u s / u s 2 to 4 -m h z / in te rn is t c o n v e n ie n c e / s u rg e ry l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s 1 , ( + / ): n u m b e r o f p a ti e n t w it h p le u ra l e ff u si o n / n u m b e r o f p a ti e n t w it h o u t p le u ra l e ff u si o n ; 2 , n u m b e r a re p re se n te d a s m e a n ± s ta n d a rd d e v ia ti o n o r (r a n g e ). c t : c o m p u te d t o m o g ra p h y ; c x r : c h e st r a d io g ra p h y ; e p : e m e rg e n cy p h y si ci a n ; n a : n o t a p p li ca b le ; n r : n o t r e p o rt e d ; u s : u lt ra so n o g ra p h y . http://acr.sagepub.com/search?author1=stephan+schleder&sortspec=date&submit=submit http://tumj.tums.ac.ir/search.php?slc_lang=en&sid=1&auth=kasraei this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 4 obtain further articles and data. only original articles were included. the studies that had used radiography as their reference test were excluded and only surveys in which a final diagnosis of pleural effusion had been confirmed by computed tomography scan or surgery were included. the search yielded three surveys which had compared the diagnostic value of pocket-size ultrasonography machines with high-end ones. since these high-end ultrasonography machine had been performed by cardiologists and their results had been assessed by the final diagnosis proposed by two specialists as the reference test, these three surveys were also included in the meta-analysis. data extraction the articles were entered into endnote x7 software and after elimination of duplicates, two reviewers (m.y, p.g) independently screened the articles. full texts of the articles were studied and summarization was done. quality of the surveys were evaluated according to the guidelines proposed by 14-item quality assessment of diagnostic accuracy studies (quadas2) tool (18). each article was assessed regarding presence of various biases including selection, performance, recording, and reporting and they were classified as three grades of poor, fair or good. only fair and good surveys were included in metaanalysis. data on distribution of the study population regarding age and gender, sample size, the number of patients with/without pleural effusion according to reference tests, technique of ultrasonography, the specialty of the ultrasound device’s operator, sonographic definition of pleural effusion, probe’s frequency, blinding status, sampling method (consecutive, convenience) and finally number of true and false, positive and negative cases were gathered. a third author (m.h) was in charge of solving disagreements. in cases where data were not presented in the article web-based programs were used to compute true positive, false positive, true negative and false negative figures according to sensitivity and specificity. when available, data for each hemi-thorax were included in the analysis separately. statistical analysis stata 11.0 statistical software was used to analyze the data via midas module. to evaluate the adequacy of ultrasonography and radiography in detection of pleural effusion, summary receiver operative curves (sroc), sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (95% ci) were calculated using a mixed-effects binary regression model. heterogeneity between the included surveys was assessed through utilization of i2 and χ2 tests and a p value of less than 0.1 along with an i2 greater than 50% were considered as positive heterogeneity (19). consequently, subgroup analysis was performed on sampling method (consecutive/ convenience), operator (emergency physician/ other specialists) or interpreting physician, frequency of the probe (1-5 mhz/ 5-10 mhz), type of ultrasound device (pocket-size/other) and sample size (less than 100 patients/ more than 100 patients). results: study characteristics search process and the number of articles obtained in each step are presented in figure 1. twenty one studies met the inclusion criteria. one survey was also found through manual search. after detailed evaluation of these surveys 12 studies were included in meta-analysis (3-5, 7-10, 13-17). the characteristics of included studies are presented in table 1. the mean age of the subjects was 63.3 years (ranging from 14 to 101 years old) and 58.6% were male. all the studies were single-center (35, 7-10, 14-17)except one which was performed in two center (13). a total of 646 patients with pleural effusion and 912 subjects without it were evaluated. diagnostic accuracy of both these modalities was assessed in nine surveys (3-5, 8-10, 13-17), radiography was evaluated individually in one study (7) and ultrasonography was assessed individually in two articles (10, 17). 11 articles were in english (3-5, 7-10, 13-15, 17) and one was in farsi (16). the presence of heterogeneity was confirmed between the studies (p<0.1), but no publication bias was detected (figure 2). meta-analysis area under the curve of srocs for ultrasonography and chest radiography in detection of pleural effusion were 0.98 (95% ci: 0.97-0.99) and 0.73 (95% ci: 0.69-0.77), respectively (figure 3). pooled sensitivity and specificity of ultrasonography in detection of pleural effusion were 0.94 (95% ci: 0.88-0.97; i2= 84.23, p<0.001) and 0.98 (95% ci: 0.92-1.0; i2= 88.65, p<0.001), respectively. also, its pooled positive and negative likelihood ratios were calculated to be 53.96 (95% ci: 11.46-254.05; i2= 88.12, p<0.001) and 0.06 (95% ci: 0.03-0.12; i2= 84.44, p<0.001), respectively (figure 4). pooled sensitivity and specificity of radiography in pleural effusion diagnosis were 0.51 (95% ci: 0.33-0.68; i2= 91.76, p<0.001) and 0.91 (95% ci: 0.68-0.98; i2= 92.86, p<0.001), respectively. in addition, its pooled positive and negative likelihood ratios were also found to be 5.60 (95% ci: 1.14-27.42; i2= 88.14, p<0.001) and 0.54 (95% ci: 0.35-0.84; i2= 84.44, p<0.001), respectively (figure 5). subgroup analysis subgroups analyses were performed regarding study design, patients’ type (critically ill / other), operator of ultrasound machine, ultrasound model and sample size. the results showed that the sensitivity was higher when the procedure was performed via an intensivist or a radiologist, using 5-10 mhz transducers, whereas it was this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 5 emergency (2016); 4 (1): 1-10 t a b le 2 : s u b g ro u p a n a ly si s o f d ia g n o st ic a cc u ra cy f o r ch e st r a d io g ra p h y a n d u lt ra so n o g ra p h y i n d e te ct io n o f p lu ra l e ff u si o n c o v a r ia te n o . o f s tu d ie s b iv a r ia te r a n d o m -e ff e c t m o d e l s e n s it iv it y (9 5 % c i) p s p e c if ic it y (9 5 % c i) p h e te r o g e n e it y , i 2 p * u lt r a s o n o g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 8 0 .9 5 ( 0 .9 0 -0 .9 9 ) 0 .0 8 0 .9 7 ( 0 .9 2 -1 .0 0 ) < 0 .0 0 1 1 5 .0 % 0 .3 1 n o n co n se cu ti v e 4 0 .9 2 ( 0 .8 4 -1 .0 0 ) 1 .0 0 ( 0 .9 8 -1 .0 0 ) o p e r a to r r a d io lo g is t/ in te n si v is t 6 0 .9 7 ( 0 .8 3 -0 .9 6 ) < 0 .0 0 1 0 .9 9 ( 0 .9 8 -1 .0 0 ) 0 .3 4 6 8 .0 % 0 .0 5 o th e r p h y si ci a n 6 0 .9 0 ( 0 .8 3 -0 .9 6 ) 0 .9 4 ( 0 .8 6 -1 .0 0 ) s a m p le s iz e < 1 0 0 8 0 .9 4 ( 0 .8 9 -0 .9 9 ) 0 .2 2 0 .9 6 ( 0 .9 0 -1 .0 0 ) < 0 .0 0 1 0 .0 % 0 .3 8 ≥ 1 0 0 4 0 .9 4 ( 0 .8 8 -1 .0 0 ) 0 .9 9 ( 0 .9 8 -1 .0 0 ) f r e q u e n c y 1 -5 m h z 9 0 .9 2 ( 0 .8 6 -0 .9 7 ) 0 .0 4 0 .9 8 ( 0 .9 5 -1 .0 0 ) 0 .1 4 4 2 .0 % 0 .1 8 5 -1 0 m h z 3 0 .9 8 ( 0 .9 5 -1 .0 0 ) 0 .9 9 ( 0 .9 6 -1 .0 0 ) p a ti e n ts c ri ti ca ll y i ll 7 0 .9 4 ( 0 .8 9 -0 .9 9 ) 0 .2 9 0 .9 8 ( 0 .9 5 -1 .0 0 ) 0 .1 2 1 5 .0 % 0 .3 1 o th e r 5 0 .9 3 ( 0 .8 7 -1 .0 0 ) 0 .9 8 ( 0 .9 4 -1 .0 0 ) m a c h in e t y p e p o ck e tsi z e 3 0 .9 0 ( 0 .8 0 -1 .0 0 ) 0 .0 9 0 .9 2 ( 0 .7 6 -1 .0 0 ) 0 .5 5 1 6 .0 % 0 .3 0 o th e r 9 0 .9 5 ( 0 .9 1 -0 .9 9 ) 0 .9 7 ( 0 .9 7 -1 .0 0 ) r a d io g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 7 0 .5 0 ( 0 .3 0 -0 .7 1 ) 0 .9 3 0 .8 1 ( 0 .3 1 -1 .0 0 ) 0 .9 4 0 .0 % 0 .7 7 n o n co n se cu ti v e 3 0 .5 3 ( 0 .1 3 -0 .9 2 ) 0 .9 3 ( 0 .8 1 -1 .0 0 ) o p e r a to r r a d io lo g is t/ in te n si v is t 6 0 .5 0 ( 0 .2 7 -0 .7 3 ) 0 .9 5 0 .8 7 ( 0 .6 5 -1 .0 0 ) 0 .9 5 0 .0 % 0 .7 3 o th e r 4 0 .5 1 ( 0 .2 2 -0 .8 1 ) 0 .9 6 ( 0 .8 4 -1 .0 0 ) s a m p le s iz e < 1 0 0 6 0 .4 5 ( 0 .2 2 -0 .6 7 ) 0 .4 4 0 .7 9 ( 0 .5 1 -1 .0 0 ) 0 .9 9 8 .0 % 0 .3 4 ≥ = 1 0 0 4 0 .6 0 ( 0 .3 3 -0 .8 7 ) 0 .9 7 ( 0 .9 0 -1 .0 0 ) p a ti e n ts c ri ti ca ll y i ll 7 0 .4 8 ( 0 .2 6 -0 .6 9 ) 0 .6 2 0 .8 2 ( 0 .5 9 -1 .0 0 ) 0 .2 9 1 2 .0 % 0 .3 2 o th e r 3 0 .5 8 ( 0 .2 5 -0 .9 1 ) 0 .9 8 ( 0 .9 3 -1 .0 0 ) *, p v a lu e < 0 .1 w a s co n si d e re d a s si g n if ic a n t fo r h e te ro g e n e it y ; c i: c o n fi d e n c e i n te rv a l. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 6 lower when carried out via pocket-size devices. on the other hand, the specificity of this modality was not influenced by any of these factors. the diagnostic value of radiography was affected by the sample size and type of patients. in this regard, the sensitivity and specificity of chest radiography was found to be higher in studies with sample sizes of greater than 100 patients while both of these measures were calculated to be lower in critically ill patients (table 2). discussion: the present meta-analysis showed that ultrasonography has high sensitivity (94%) and specificity (98%) in detection of pleural effusion. when the analysis was limited to the surveys in which the procedure was carried out by an intensivist or a radiologist, the presented sensitivity increased (98%). while, the diagnostic value of radiography was reported to be lower than ultrasonography (sensitivity 51%, specificity 91%). when we limited the analyses to studies in which the etiology of pleural effusion was trauma, surgery or congestive heart failure, sensitivity of radiography slightly increased (58%). on this basis it can be concluded that ultrasonography is a better diagnostic tool for pleural effusion compared to radiography. in comparison with the results of the present study, grimberg et al. reported similar results in their review of four articles. they found the sensitivity and specificity of ultrasonography to be 93% and 96% respectively while these figures for radiography were calculated to be 24% and 100% (11). our results were almost similar to grimberg’s et al. study. the higher sensitivity of radiography presented in this study might be due to inclusion of more surveys in the analyses. grimberg’s survey lacked subgroup analysis which prevents us from further comparisons. in another meta-analysis chavez et al. reviewed 10 articles aiming to evaluate the diagnostic value of ultrasonography in detection of pneumonia and they found a sensitivity of 94% and a specificity of 96% for this modality (20). these researchers stated that ultrasonography is a suitable diagnostic tool for ruling out pneumonia in patients referring to medical centers and emergency departments. congruent with this survey we also found a considerable diagnostic value for ultrasonography in detection of pleural effusion. one of the factors that influence sensitivity of ultrasonography is the operator of ultrasound device which has been verified by various surveys in the past years (2124). an ultrasonography carried out by an intensivist or a radiologist is able to detect pleural effusion more effectively and precisely. pocket-size ultrasonography is a new technology recently being used in some medical centers and reported to be an effective modality in diagnostic procedures (2527). this machine transmits high resolution pictures that help physicians to make more precise decisions regarding the patients’ pathology (28, 29). accordingly, we found three studies which assess the diagnostic accuracy of pocket-size ultrasonography for pleural effusion (9, 10, 17), in two of which the procedure was performed by a trained nurse (9, 10) and in one it was carried out by an internal medicine specialist (17). the first two reported a sensitivity of approximately 92-98% and the latter survey found a sensitivity of 62% in detection of pleural effusion. this inconsistency might have been due to the different study populations. graven et al. and dalen et al. only included cardiac patients while stock et al. evaluate patients with various diseases. nevertheless, the sample sizes of all the three surveys were small and so further investigation is required for application of this ultrasonography device in clinical settings. in this meta-analysis the extended search in databases and bibliographies yielded 12 relevant articles. although few studies were included in this study, but the large sample population of 1554 subjects assured the validity of performed analyses to a great extent. presence of no publication bias confirms this declaration. heterogeneity between the articles was another limitation of this survey which was attempted to overcome through application of mixed-effects binary regression model and subgroup analysis. simultaneous inclusion of retrospective and prospective surveys was probable limitation of this study, but the scatterplot developed to evaluate the outlier studies according to standardized predicted random effects showed that retrospective surveys were not the source of diversity between the included articles. conclusion: the present meta-analysis found chest ultrasonography to have a considerably higher screening value in detection of pleural effusion compare to radiography. being performed by an intensivist or a radiologist and using probes with frequencies of 5-10mhz improves the sensitivity of this imaging modality. acknowledgments: none conflict of interest: none funding support: this research has been supported by tehran university of medical sciences & health services grant number: 9302-38-25618. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 7 emergency (2016); 4 (1): 1-10 references: 1. rozycki gs, pennington sd, feliciano dv. surgeonperformed ultrasound in the critical care setting: its use as an extension of the physical examination to detect pleural effusion. j trauma. 2001;50(4):636-42. 2. rozycki gs, cava ra, tchorz km. surgeon-performed ultrasound imaging in acute surgical disorders. curr probl surg. 2001;38(3):141-212. 3. kataoka h, takada s. the role of thoracic ultrasonography for evaluation of patients with decompensated chronic heart failure. j am coll cardiol. 2000;35(6):1638-46. 4. lichtenstein d, goldstein i, mourgeon e, cluzel p, grenier p, rouby jj. comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome. anesthesiology. 2004;100(1):9-15. 5. ma oj, mateer jr. trauma ultrasound examination versus chest radiography in the detection of hemothorax. ann emerg med. 1997;29(3):312-6. 6. villena garrido v, cases viedma e, fernandez villar a, et al. recommendations of diagnosis and treatment of pleural effusion. update. arch bronconeumol. 2014;50(6):235-49. 7. kitazono mt, lau ct, parada an, renjen p, miller jr wt. differentiation of pleural effusions from parenchymal opacities: accuracy of bedside chest radiography. am j roentgenol. 2010;194(2):407-12. 8. rocco m, carbone i, morelli a, et al. diagnostic accuracy of bedside ultrasonography in the icu: feasibility of detecting pulmonary effusion and lung contusion in patients on respiratory support after severe blunt thoracic trauma. acta anaesthesiol scand. 2008;52(6):776-84. 9. graven t, wahba a, hammer am, et al. focused ultrasound of the pleural cavities and the pericardium by nurses after cardiac surgery. scand cardiovasc j. 2015;49(1):56-63. 10. dalen h, gundersen gh, skjetne k, et al. feasibility and reliability of pocket-size ultrasound examinations of the pleural cavities and vena cava inferior performed by nurses in an outpatient heart failure clinic. eur j cardiovasc nurs. 2015;14(4):286-93. 11. grimberg a, shigueoka dc, atallah an, ajzen s, iared w. diagnostic accuracy of sonography for pleural effusion: systematic review. sao paulo med j. 2010;128(2):90-5. 12. stroup df, berlin ja, morton sc, et al. meta-analysis of observational studies in epidemiology: a proposal for reporting. meta-analysis of observational studies in epidemiology (moose) group. jama. 2000;283(15):2008-12. 13. zanobetti m, poggioni c, pini r. can chest ultrasonography replace standard chest radiography for evaluation of acute dyspnea in the ed? chest. 2011;139(5):1140-7. 14. xirouchaki n, magkanas e, vaporidi k, et al. lung ultrasound in critically ill patients: comparison with bedside chest radiography. intensive care med. 2011;37(9):1488-93. 15. schleder s, dornia c, poschenrieder f, et al. bedside diagnosis of pleural effusion with a latest generation handcarried ultrasound device in intensive care patients. acta radiol. 2012;53(5):556-60. 16. kasraei m, abtahi h, eyoobi yazdi n, safavi e, firoozbakhsh s, mohammady m. diagnosis of pleural effusion by portable ultrasound and chest radiography in intensive care unit. tehran uni med j. 2014;72(7):463-70. [persian]. 17. stock kf, klein b, steubl d, et al. comparison of a pocketsize ultrasound device with a premium ultrasound machine: diagnostic value and time required in bedside ultrasound examination. abdom imaging. 2015:[in press]. 18. whiting pf, rutjes aw, westwood me, et al. quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies. ann intern med. 2011;155(8):529-36. 19. higgins jp, thompson sg, deeks jj, altman dg. measuring inconsistency in meta-analyses. bmj. 2003;327(7414):557. 20. chavez ma, shams n, ellington le, et al. lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. respir res. 2014;15:50-9. 21. abbasi s, farsi d, hafezimoghadam p, fathi m, zare ma. accuracy of emergency physician-performed ultrasound in detecting traumatic pneumothorax after a 2-h training course. eur j emerg med. 2013;20(3):173-7. 22. bui-mansfield lt, chen dc, o'brien sd. accuracy of ultrasound of musculoskeletal soft-tissue tumors. am j roentgenol. 2015;204(2):w218-22. 23. fine d, perring s, herbetko j, hacking c, fleming j, dewbury k. three-dimensional (3d) ultrasound imaging of the gallbladder and dilated biliary tree: reconstruction from realtime b-scans. br j radiol. 1991;64(767):1056-7. 24. lee jh, jeong yk, park kb, park jk, jeong ak, hwang jc. operator-dependent techniques for graded compression sonography to detect the appendix and diagnose acute appendicitis. am j roentgenol. 2005;184(1):91-7. 25. kobal sl, trento l, baharami s, et al. comparison of effectiveness of hand-carried ultrasound to bedside cardiovascular physical examination. am j cardiol. 2005;96(7):1002-6. 26. skjetne k, graven t, haugen bo, salvesen o, kleinau jo, dalen h. diagnostic influence of cardiovascular screening by pocket-size ultrasound in a cardiac unit. eur j echocardiogr. 2011;12(10):737-43. 27. tofield a. the use of pocket size imaging devices: a position statement by the european association of echocardiography. eur heart j. 2011;32(4):385-6. 28. andersen gn, haugen bo, graven t, salvesen o, mjolstad oc, dalen h. feasibility and reliability of point-of-care pocketsized echocardiography. eur j echocardiogr. 2011;12(9):66570. 29. mjolstad oc, andersen gn, dalen h, et al. feasibility and reliability of point-of-care pocket-size echocardiography performed by medical residents. eur heart j cardiovasc imaging. 2013;14(12):1195-202. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 8 a b figure 2: deeks’ funnel plot asymmetry test for assessment of publication bias. p values < 0.05 were considered as significant. ultrasonography (a); radiography (b). ess: effective sample sizes. a b figure 3: summary receiver operative curves (sroc) for ultrasound (a) and chest radiography (b) in detection of plural effusion. auc: area under the curve; sens: sensitivity; spec: specificity. 1 2 3 4 5 6 7 8 9 10 11 12 .05 .1 .15 .2 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.80 1 2 3 4 5 6 7 8 9 10 .05 .1 .15 .2 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.76 1 2 3 4 5 6 7 8 9 10 11 12 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.94 [0.88 0.97] spec = 0.98 [0.92 1.00] sroc curve auc = 0.98 [0.97 0.99] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours 1 2 3 4 5 6 7 8 9 10 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.51 [0.33 0.68] spec = 0.91 [0.68 0.98] sroc curve auc = 0.73 [0.69 0.77] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 9 emergency (2016); 4 (1): 1-10 a b figure 4: forest plot of screening performance characteristics of chest ultrasonography in detection of plural effusion. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q = 69.76, df = 11.00, p = 0.00 i2 = 84.23 [76.34 92.13] 0.94[0.88 0.97] 0.62 [0.38 0.82] 0.92 [0.79 0.98] 0.98 [0.93 1.00] 1.00 [0.87 1.00] 0.91 [0.77 0.98] 1.00 [0.94 1.00] 0.84 [0.64 0.95] 0.95 [0.82 0.99] 0.92 [0.85 0.96] 0.90 [0.83 0.96] 0.90 [0.79 0.96] 0.96 [0.80 1.00]0.96 [0.80 1.00] author / year combined stock 2015 dalen 2015 graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 rocco 2008 lichtenstein 2004 rozycki 2001 kataoka 2000 ma 1997 0.4 1.0 specificity (95% ci) q = 96.90, df = 11.00, p = 0.00 i2 = 88.65 [83.46 93.83] 0.98[0.92 1.00] 0.89 [0.52 1.00] 0.99 [0.94 1.00] 0.70 [0.47 0.87] 1.00 [0.59 1.00] 1.00 [0.75 1.00] 1.00 [0.84 1.00] 0.73 [0.39 0.94] 0.99 [0.96 1.00] 0.93 [0.89 0.96] 1.00 [0.92 1.00] 0.95 [0.77 1.00] 1.00 [0.98 1.00]1.00 [0.98 1.00] author / year combined stock 2015 dalen 2015 graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 rocco 2008 lichtenstein 2004 rozycki 2001 kataoka 2000 ma 1997 0.4 1.0 dlr positive (95% ci) q = 88.12, df = 11.00, p = 0.00 i2 = 81.66 [81.66 93.37] 53.96[11.46 254.05] 5.57 [0.85 36.44] 78.46 [11.16 551.76] 3.22 [1.73 5.97] 15.71 [1.07 230.17] 25.28 [1.66 385.25] 43.66 [2.82 676.25] 3.08 [1.16 8.21] 134.53 [19.05 949.80] 13.06 [8.53 20.01] 84.60 [5.37 1000] 19.80 [2.91 134.62] 406.11 [25.45 1000]406.11 [25.45 1000] author / year combined stock 2015 dalen 2015 graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 rocco 2008 lichtenstein 2004 rozycki 2001 kataoka 2000 ma 1997 0.9 1000.0 dlr negative (95% ci) q = 70.67, df = 11.00, p = 0.00 i2 = 84.44 [76.67 92.20] 0.06[0.03 0.12] 0.43 [0.24 0.77] 0.08 [0.03 0.23] 0.03 [0.01 0.12] 0.02 [0.01 0.30] 0.10 [0.04 0.27] 0.01 [0.01 0.13] 0.22 [0.08 0.58] 0.05 [0.01 0.20] 0.09 [0.04 0.17] 0.10 [0.06 0.18] 0.10 [0.05 0.23] 0.06 [0.01 0.26]0.06 [0.01 0.26] author / year combined stock 2015 dalen 2015 graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 rocco 2008 lichtenstein 2004 rozycki 2001 kataoka 2000 ma 1997 0 1 this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com yousefifard et al 10 a b figure 5: forest plot of screening performance characteristics of chest radiography in detection of plural effusion. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q =106.76, df = 9.00, p = 0.00 i2 = 91.57 [87.67 95.47] 0.51[0.33 0.68] 0.40 [0.30 0.51] 0.33 [0.17 0.54] 0.74 [0.57 0.88] 0.65 [0.52 0.77] 0.16 [0.05 0.36] 0.66 [0.61 0.70] 0.24 [0.11 0.40] 0.39 [0.29 0.49] 0.43 [0.31 0.57] 0.96 [0.80 1.00]0.96 [0.80 1.00] author / year combined graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 kitazono 2010 rocco 2008 lichtenstein 2004 kataoka 2000 ma 1997 0.0 1.0 specificity (95% ci) q =126.09, df = 9.00, p = 0.00 i2 = 92.86 [89.72 96.00] 0.91[0.68 0.98] 0.78 [0.56 0.93] 1.00 [0.59 1.00] 0.31 [0.09 0.61] 0.81 [0.58 0.95] 0.27 [0.06 0.61] 0.89 [0.85 0.92] 0.96 [0.91 0.98] 0.85 [0.81 0.89] 1.00 [0.85 1.00] 1.00 [0.98 1.00]1.00 [0.98 1.00] author / year combined graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 kitazono 2010 rocco 2008 lichtenstein 2004 kataoka 2000 ma 1997 0.1 1.0 dlr positive (95% ci) q =110.63, df = 9.00, p = 0.00 i2 = 88.14 [88.14 95.59] 5.60[1.14 27.42] 1.84 [0.82 4.15] 5.43 [0.35 83.50] 1.07 [0.71 1.62] 3.42 [1.39 8.40] 0.22 [0.08 0.58] 5.96 [4.35 8.17] 5.61 [2.13 14.77] 2.64 [1.82 3.82] 19.98 [1.27 314.61] 406.11 [25.45 1000]406.11 [25.45 1000] author / year combined graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 kitazono 2010 rocco 2008 lichtenstein 2004 kataoka 2000 ma 1997 0.1 1000.0 dlr negative (95% ci) q = 87.40, df = 9.00, p = 0.00 i2 = 89.70 [84.66 94.75] 0.54[0.35 0.84] 0.77 [0.58 1.00] 0.70 [0.51 0.97] 0.84 [0.31 1.00] 0.43 [0.29 0.64] 3.08 [1.16 1.00] 0.39 [0.34 0.44] 0.80 [0.67 0.95] 0.72 [0.61 0.84] 0.58 [0.46 0.73] 0.06 [0.01 0.26]0.06 [0.01 0.26] author / year combined graven 2015 kasraei 2014 schleder 2012 xirouchaki 2011 zanobetti 2011 kitazono 2010 rocco 2008 lichtenstein 2004 kataoka 2000 ma 1997 0 3 emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 16 emergency (2016); 4 (1): 16-20 original research knowledge and attitude of iranian red crescent society volunteers in dealing with bioterrorist attacks seyed ali bahreini moghadam1, siavash hamzeh pour2*, mahmoud toorchi3, youssof sefidi heris2 1. department of hospital management, shohadaye tajrish hospital, tehran, iran. 2. department of biology, higher education institute of rabe – rashid, tabriz, iran. 3. department of biotechnology, university of tabriz, tabriz, iran. *corresponding author: siavash hamzeh pour, bs. of biochemistry, department of biology, higher education institute of rabe – rashid, tabriz, iran. tel: +98444-2334788; cell phone: +989362477193; email: hseavash@yahoo.com received: march 2015; accepted: may 2015 abstract introduction: bioterrorism is a worldwide problem and has been the focus of attention during recent decades. there is no precise information on the knowledge, attitude, and preparedness of iranian red crescent volunteers in dealing with bioterrorism. therefore, the present study aimed to evaluate the above-mentioned parameters in mahabad red crescent society volunteers. methods: in this prospective cross-sectional study, the knowledge of 120 volunteers was evaluated and rated as poor, moderate, and good. in addition, attitude of the volunteers and preparedness of mahabad red crescent society was rated as inappropriate and appropriate using a questionnaire. results: the mean age of volunteers was 32.0 ± 8.2 years (62.5% male). 2 (1.7%) volunteers had good knowledge while 94 (78.3%) had no knowledge regarding bioterrorist attack management. only 1 (0.8%) volunteer had appropriate attitude and 6 (5.0%) stated their preparedness for being sent out to the crisis zone. 116 volunteers (96.7%) indicated that mahabad red crescent society has an inappropriate level of preparedness to encounter bioterrorist attacks. conclusion: the findings of the present study showed poor knowledge and inappropriate attitude of mahabad red crescent society volunteers in encountering probable bioterrorist attacks. furthermore, the red crescent society of this town had an inappropriate level of preparedness in the field of bioterrorism from the viewpoint of the studied volunteers. key words: bioterrorism; knowledge; civil defense; rescue work cite this article as: bahreini moghadam sa, hamzeh pour s, toorchi m, sefidi heris y. knowledge and attitude of iranian red crescent society volunteers in dealing with bioterrorist attacks. emergency. 2016;4(1):16-20 introduction: ioterrorism can be generally defined as the abuse of biological and microbial agents or their products to terrify or kill humans or animals. limited bioterrorist actions are precedent from a long time ago, but recently it has been broadly introduced into medical and hygienic circles (1-3) and has compelled researchers to prioritize preventive measures in this regard (4-7). despite the rare probability of a biological war, it cannot be ignored (8, 9). biological terrorist attack of tokyo subway, 1995, caused 11 cases of death and thousands of hospitalization cases (10). following the event of september 11, 2001, the risk of a bioterrorist attack has become a real concern among rescue task forces. one theoretical model in the united states declared that if a terrorist attack with biologic agents happened in a crowded city, it could lead to a mortality rate up to 32000/100000 (11). decreasing post-disaster morbidity and mortality depends on sufficient resources and acceptable level of knowledge, attitude, and preparedness among rescue task forces (1214). in iran, red crescent society is the most important organization in dealing with probable terrorist attacks. nevertheless, at the time of bioterrorist attacks, its volunteers may have to confront difficulties such as identification of unknown microbial agents as well as working with limited equipment and in unknown environments (15). to date, there is no precise information regarding knowledge, attitude, and preparedness of iranian relief task force volunteers in management of probable bioterrorist attacks. therefore, the aim of this study was to evaluate knowledge, attitude, and preparedness level of iranian red crescent society volunteers in biological and bioterrorist attack. b this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 17 emergency (2016); 4 (1): 16-20 methods: study design and setting the present study is a prospective cross-sectional study on knowledge, attitude, and preparedness level of mahabad (northwest iran) red crescent society volunteers, in 2014. the required information was collected through a questionnaire, reliability of which was verified using a 40-case pilot study and test-retest method (r = 0.78). expert panel confirmed face, criterion, and content validity of the questionnaire. the first part of the questionnaire included three questions regarding demographic data such as age, sex, and education. the second part of it included 18 two-choice questions in three fields: volunteers’ knowledge (four questions), volunteers’ attitude to participate in rescue teams at the time of bioterrorist attacks (six questions), and the preparedness of red crescent society in dealing with bioterrorist attacks from volunteers’ viewpoint (eight questions) (table 1). table 1: the questions queried about the volunteers’ knowledge, attitude, and the preparedness of respective organization about bioterrorist attacks the question no (%) yes (%) knowledge 1are you familiar with bioterrorism threats (biological disasters)? 111 (62.5) 9 (7.5) 2are you familiar with causative and pathogenic bioterrorism agents? 114 (95.0) 6 (5.0) 3are you familiar with diagnostic and therapeutic methods at the event of encountering bioterrorism agents? 120 (100) 0 (0.0) 4do you believe the central upper management is partly responsible for the lack of education and consequently lack of intervention in urgent biological disasters? 45 (35.0) 75 (62.5) attitude 1are you committed to staying at work at the event of a bioterrorist or biological attack? 113 (94.2) 7 (5.8) 2do you tend to care and treat the probable victims at the event of a bioterrorist or biological attack? 117 (97.5) 3 (20.5) 3do you tend to cooperate with your respective organization in biological defense (anti-bioterrorism) plans? 115 (95.8) 5 (4.2) 4if the personal protective clothing and complete isolation equipment are supplied, do you tend to work (able to take a role) in the area contaminated with pathogenic agent? 108 (90) 12 (10) 5do you tend to participate in workshops and conferences related with bioterrorism? 104 (86.7) 16 (13.3) 6do you tend to pass university courses or in-service training courses with the content of anti-bioterrorism defense? 117 (97.5) 3 (2.5) organization preparation 1has your organization held retraining workshops and seminars in the field of biological defense and bioterrorism? 100 (100) 0 (0.0) 2has a recorded and official instruction, proclamation, or training course been explained on how to intervene in biological and bioterrorist attacks? 118 (98.3) 2 (1.7) 3does the organization you serve, provide the required financial supports for you at the time of encountering biological and bioterrorist attacks? 119 (99.2) 1 (0.8) 4does the organization you serve, consider your worries and concerns about the security of yourself and your family at the time of facing biological and bioterrorist attacks? 110 (91.7) 10 (8.3) 5does the central organization (in tehran) consider your concerns and needs at the time of educational and strategic planning for preparedness against bioterrorist attacks? 97 (80.8) 23 (19.2) 6do you believe material and spiritual encouragements by the upper management are necessary for better performance (quantitatively and qualitatively) at the event of bioterrorist attacks? 95 (79.2) 25 (20.8) 7what is your general attitude toward the preparedness level of relief and intervention teams at the event of a biological emergency? 120 (100) 0 (0.0) 8do you have the required preparedness to be sent out to the zone of crisis if you are needed at the event of a biological attack in any part of the country? 114 (95.0) 6 (5.0) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com bahreini moghadam et al 18 the protocol of this study was approved by the local ethics committee of red crescent society. the investigators adhered to the principles of helsinki declaration. the informed written consent form was signed by the volunteers. participants: the studied population included volunteers who had passed at least one rescue course (consisting of 4 different 2-day workshops) in disaster management. 120 volunteers were selected using simple random sampling. volunteers who did not want to participate or filled the forms incompletely were excluded. statistical analysis the required sample size was determined to be at least 77 cases considering the 72% prevalence (p = 0.72) of poor knowledge (12), α = 0.05, and desired precision of 0.1 (d = 0.1). the data were analyzed using spss 21.0. the quantitative data were reported as mean and standard deviation, and the qualitative ones were reported as frequency and percentage. each positive answer to the questions gained 1 point, while negative answers received 0 points. therefore, the maximum achievable scores for knowledge, attitude, and preparedness were 4, 6, and 8, respectively. the knowledge score 0 was considered as poor, 1 and 2 as moderate, and 3 and 4 as good knowledge. in addition, the attitude score ≤ 3 was defined as inappropriate and score > 3 as appropriate attitude. the preparedness level was rated inappropriate if preparedness score was 0-4 and appropriate if it was 5-8. results: 120 volunteers of iranian red crescent society were questioned (62.5% male). mean age of the volunteers was 32 ± 8.2 years (range: 20-51 years). 34 (28.3%) of the participants had diploma, 25 (20.8%) had associate degree, 52 (43.3%) had bachelor’s degree, and 9 (7.5%) had master’s degree or higher. none of the volunteers had any information regarding management of biologic agents. table 1 summarizes the frequency of positive and negative responses to the 18 mentioned questions. knowledge: 9 (7.5%) cases had knowledge about bioterrorism threats. 6 (5.0%) cases had knowledge about causative and pathogenic characteristics of biologic agents. 2 (1.7%) cases had good knowledge about bioterrorist attacks and their management (figure 1). while 94 (78.3%) cases had no knowledge about how to encounter and manage bioterrorist attacks. attitude: 7 (5.8%) cases would stay at work during a bioterrorist attack. five (4.2%) cases had the tendency to cooperate with the responsible organizations and 12 (10.0%) cases declared that they would participate if protective equipment were available. three (2.5%) cases were willing to take care of the probable victims of bioterrorist attacks. figure 1: the volunteers’ knowledge regarding management of bioterrorist attacks. only one (0.8%) volunteer had an appropriate attitude and 119 (99.2%) had inappropriate attitude toward participation in bioterrorism relief task forces. preparedness: based on volunteers’ answers, no training workshops and seminars had been held so far regarding biological and bioterrorist attacks. one (0.8%) case stated that the red crescent society provided the required financial supports for facing biological and bioterrorist attacks. two (1.7%) cases declared that recorded instructions, guideline, or training courses had been explained by the central organization. ten (8.3%) cases expressed that the respective organization had considered their worries and concerns about the security of their own selves and their families at the time of facing biological and bioterrorist attacks. 23 (19.2%) cases said that the central organization considered the personal requirements during educational planning for preparedness against bioterrorist attacks. from the viewpoint of 116 (96.7%) volunteers, mahabad red crescent society had inappropriate preparedness to encounter bioterrorist attacks (figure 2). figure 2: the preparedness of mahabad red crescent society to encounter bioterrorist attacks from the volunteers’ viewpoint. 78.3 12.5 5 3.4 0.8 0 10 20 30 40 50 60 70 80 90 0 1 2 3 4 p e rc e n ta g e o f v o lu n te e rs knowledge score 70.83 13.33 10 2.5 1.67 1.67 0 10 20 30 40 50 60 70 80 0 1 2 3 4 5 p e rc e n ta g e o f v o lu n te e rs preparedness score this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 19 emergency (2016); 4 (1): 16-20 discussion: the findings of this study showed that only 1.7% of the iranian red crescent society volunteers had good knowledge about management of bioterrorist attacks. 99.2% had inappropriate attitude, and 96.7% believed that preparedness of mahabad red crescent society is poor about encountering bioterrorist attacks. the findings of present study is in line with previous investigations in this regard (13, 14). in an evaluation of nurses’ awareness about bioterrorism agents, 72.5% had poor knowledge in this field (12). in addition, an investigation in 2002 concluded that physicians did not have the necessary and satisfactory level of knowledge in bioterrorism management and declared the necessity of training courses in this regard (16). one study showed that higher knowledge of rescuers increased their tendency to respond in bioterrorist attacks (17). thus, training the volunteers is of high importance in order to increase their willingness for relief in contaminated areas. holding different scientific seminars and symposiums and fitting different training plans in the field of bioterrorism as optional courses into syllabuses of universities and responsible organizations, can be a worthy donation to elevate the knowledge level of society’s experts. in iran, red crescent society along with military forces are on the frontline of biological and anti-bioterrorist defense. they must provide necessary resources such as antidotes, antibiotics, antitoxins, and intensive care equipment like ventilators. at the time of bioterrorist attacks, quick and timely response is so important that even seconds can save thousands of lives. the required facilities and equipment for combating against bioterrorist attacks must always be prepared and ready to work to prevent waste of time in such events. during such disasters, there is an increase in consumption of resources and some rarely-used equipment, which causes shortage of equipment during a bioterrorist attack (18). unfortunately, based on the viewpoint of the study participants, we are faced with inappropriate preparedness of mahabad red crescent society in dealing with bioterrorist attacks, which requires special attention to improve. finally, it is thought that elevating the knowledge and attitude of health care providers and training them in the backbone field of biological defense can result in a better and more efficient battle against probable bioterrorist attacks. conclusion: the findings of the present study showed poor knowledge and inappropriate attitude of mahabad red crescent society volunteers in encountering with probable bioterrorist attacks. furthermore, the red crescent society of this town had an inappropriate level of preparedness in the field of bioterrorism from the viewpoint of the studied volunteers. acknowledgments: the authors appreciate the insightful cooperation of dr. mahmoud yousefifard; department of physiology, school of medicine, tehran university of medical sciences, for developing the final draft of this article. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. bravata dm, mcdonald km, smith wm, et al. systematic review: surveillance systems for early detection of bioterrorism-related diseases. ann intern med. 2004;140(11):910-22. 2. henderson da. bioterrorism as a public health threat. emerg infect dis. 1998;4(3):488-92. 3. osterholm mt, scheld w, craig wa, hughes jm. bioterrorism: a real modern threat. emerg infect. 2001;5(1):213-22. 4. gershon rr, qureshi ka, sepkowitz ka, gurtman ac, galea s, sherman mf. clinicians’ knowledge, attitudes, and concerns regarding bioterrorism after a brief educational program. j occup environ med. 2004;46(1):77-83. 5. anderson pd. bioterrorism: toxins as weapons. j pharm pract. 2012;25(2):121-9. 6. longo dl, adalja aa, toner e, inglesby tv. clinical management of potential bioterrorism-related conditions. n engl j med. 2015;372(10):954-62. 7. greub g, grobusch mp. bioterrorism: myth or reality? clin microbiol infect. 2014;20(6):485-7. 8. goodier j. encyclopedia of bioterrorism defence. ref rev. 2012;26(3):34-5. 9. van courtland moon je. pathogens for war: biological weapons, canadian life scientists, and north america biodefence by donald avery (review). bull hist med. 2014;88(2):395-7. 10. riedel s. biological warfare and bioterrorism: a historical review. proc (bayl univ med cent). 2004;17(4):400-6. 11. wetter dc, daniell we, treser cd. hospital preparedness for victims of chemical or biological terrorism. am j public health. 2001;91(5):710-6. 12. rebmann t, mohr lb. bioterrorism knowledge and educational participation of nurses in missouri. j contin educ nurs. 2010;41(2):67-76. 13. brown c, editor are nurses prepared for a radiological disaster?: assessing the knowledge of nursing students to support the need of integrating radiological/disaster content into nursing curricula. sigma theta tau international's 25th international nursing research congress; 2014; hong kong: sigma theta tau international. 14. aghaei n, nesami mb. bioterrorism education effect on knowledge and attitudes of nurses. j emerg trauma shock. 2013;6(2):78-82. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com bahreini moghadam et al 20 15. eitzen em. education is the key to defense against bioterrorism. ann emerg med. 1999;34(2):221-3. 16. herold jm, peavy jv. bioterrorism: a survey assessing the level of awareness among alachua county's physicians. oxford, uk: oxford university press; 2002. p. 479-91. 17. rokach a, cohen r, shapira n, einav s, mandibura a, bardayan y. preparedness for anthrax attack: the effect of knowledge on the willingness to treat patients. disasters. 2010;34(3):637-43. 18. pesik n, keim me, iserson kv. terrorism and the ethics of emergency medical care. ann emerg med. 2001;37(6):642-6. archives of academic emergency medicine. 2022; 10(1): e80 rev i ew art i c l e epidemiology of traumatic spinal cord injuries in iran; a systematic review and meta-analysis mohsen saheban maleki1, behzad khedri2, maryam ebrahimpour roodposhti3, hesamedin askari majdabadi4,5, seyedeh omolbanin seyedrezaei6, nasir amanat4,5, mohsen poursadeqiyan7, farahnaz khajehnasiri8∗, roya amiri9 † 1. department of anesthesia, clinical research developmental unit bohlool hospital, gonabad university of medical science, gonabad, iran. 2. department of social work, social studies faculty, hanze university of applied science, groningen, netherlands. 3. trauma research center, faculty of nursing and midwifery, kashan university of medical sciences, kashan, iran. 4. nursing care research center, semnan university of medical sciences, semnan, iran. 5. department of emergency nursing, faculty of nursing & midwifery, semnan university of medical sciences, semnan, iran. 6. department of emergency medicine, school of medicine, shahroud university of medical sciences, shahroud, iran. 7. social determinants of health research center, ardabil university of medical sciences, ardabil, iran. 8. department of community medicine, school of medicine, tehran university of medical sciences, tehran, iran. 9. department of intensive care nursing, kish free zone, kish specialty & sub specialty hospital, kish, iran. received: july 2022; accepted: august 2022; published online: 6 october 2022 abstract: introduction: understanding the epidemiology of traumatic spinal cord injuries (tscis) can be helpful for policymakers and planners to consider appropriate strategies to control and prevent these injuries. this study aimed to determine the epidemiological characteristics of tsci in iran in order to increase knowledge and awareness of these injuries. methods: a systematic literature search was conducted up to january 2022 in the electronic databases, including pubmed, scopus, web of science, google scholar, sid, iranmedex, and magiran. the quality of included studies was evaluated using the storbe checklist. comprehensive meta-analysis was used to analyze the data. results: nineteen studies involving 9416 cases were included in the study. participants’ pooled mean age was 35.80 ± 1.07 years (95% ci: 33.69 to 37.91), of whom 69% (95% ci: 68% to 70%; p<0.05) were male. the most frequent tsci occurred in the age group of less than 30 years. motor vehicle collisions (mvcs) was the most common cause of tsci (57%; 95% ci: 25% to 63%), followed by falls (32%; 95% ci: 26% to 38%). most participants had thoracolumbar (27%; 95% ci: 10% to 55%) and cervical injuries (23%; 95% ci: 16% to 31%), respectively. the incidence of tsci was estimated at 10.5 per million people. the prevalence of tsci was 3 per 10000 people. the mortality rate due to tsci was 3.9% (95% ci: 0.02 to 0.06; p<0.05). conclusion: based on the findings of this meta-analysis, the pooled incidence and prevalence of tsci in the iranian population were 10.5/1000.000 people and 4.4/10.000 people, respectively. tscis had occurred more frequently in males following mvcs, and in the age group under 30 years. the pooled mortality rate due to tsci was 3.9% (95% ci: 0.02 to 0.06; p<0.05). keywords: spinal cord injuries; epidemiology; prevalence; incidence; iran cite this article as: saheban maleki m, khedri b, ebrahimpour roodposhti m, askari majdabadi h, omolbanin seyedrezaei s, et al. epidemiology of traumatic spinal cord injuries in iran; a systematic review and meta-analysis. arch acad emerg med. 2022; 10(1): e80. https://doi.org/10.22037/aaem.v10i1.1720. ∗corresponding author: farahnaz khajehnasiri, department of community medicine, school of medicine, tehran university of medical sciences, tehran, iran. e-mail: khajenasiri@tums.ac.ir, telefax: 98.21-88962357, orcid: https://orcid.org/0000-0002-4217-3685. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. saheban maleki et al. 2 1. introduction spinal cord injuries are classified into two types, traumatic and non-traumatic (1). traumatic spinal cord injuries (tsci) are one of the most severe conditions in terms of morbidity and disability (2, 3). the mortality rate in people with tsci is higher than that of normal people (4). the in-hospital mortality rate of spinal cord injuries varies from region to region (4). the most common causes of tsci are motor vehicle collisions (mvcs), falls, violence, and sports/leisure activities (5). tscis predominantly occur in males younger than 30 years old (6), and most frequently at the level of the cervical spine, followed by thoracic, and lumbosacral (7). in 2016, there were 0.93 million (0.78-1.16 million) new cases of sci, with age-based standardized incidence rates of 13 (11-16) per 100 000 people for sci (8). the incidence rate is different from one country to another (9). tsci is a costly injury for patients as the average cost for the initial injury and recovery phase of sci can be $142,366 (10). the most common symptoms in patients with tsci include pain, weakness, fatigue, and numbness (11). the most common outcomes after tsci are paralysis (12), depression (13), anxiety (14), osteoporosis (15), adverse events, including urinary tract infections, pneumonia, neuropathic pain, delirium, pressure ulcers (16), hydronephrosis, bladder stones, vesicoureteral reflux (17), hypothermia (18), cardiovascular complications, and autonomic dysreflexia (19). given that tscis vary by country and region (20), and there is no meta-analysis regarding these injuries in iran, there is an urgent need to determine the epidemiological characteristics of tscis in order to implement appropriate control and prevention strategies. this study aimed to investigate the epidemiological characteristics of tsci in the iranian population. 2. methods the meta-analysis of observational studies in epidemiology (moose) guidelines (21) were used when writing the report, and the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist was used when preparing the report (22). 2.1. literature search strategy two authors, independently, carried out a systematic literature search in the most important electronic databases, including pubmed, scopus, web of science, google scholar, † corresponding author: roya amiri; department of intensive care nursing, kish free zone, kish specialty &sub specialty hospital, kish, iran. e-mail: r.a_amiri@yahoo.com, tel: 98-76-44459400-10, fax: 98-76-44459409, orcid: https://orcid.org/0000-0003-3153-7778. sid, iranmedex, and magiran to identify the studies published in english or persian languages up to january 2022 using keywords. furthermore, the list of references of records included in the final analysis was scanned for more articles. the key search terms included traumatic spinal cord injuries, epidemiology, prevalence, incidence, risk factors, and iran. the search strategy by database was: pubmed #1. spinal cord injur* [title/abstract] or spinal cord injuries [mesh terms] #2. epidemiolog* [title/abstract] or epidemiology [mesh terms] #3. incidence [title/abstract] or incidence [mesh terms] #4. risk factor* [title/abstract] or risk factor [mesh terms] #5. prevalence [title/abstract] or prevalence [mesh terms] #6. iran [title/abstract] #7. 2 or 3 or 4 or 5 #8. 1 and 7 and 6 web of science #1. ti= (spinal cord injur*) #2. ti= (epidemiolog *) #3. ti= (incidence) #4. ti= (prevalence) #5. ti= (risk factor*) #6. ti= (iran) #7. 2 or 3 or 4 or 5 #8. 1 and 7 and 6 scopus #1. title-abs-key (spinal cord injur*) #2. title-abs-key = (epidemiolog *) #3. title-abs-key = (incidence) #4. title-abs-key = (prevalence) #5. title-abs-key = (risk factor*) #6. title-abs-key = (iran) #7. 2 or 3 or 4 or 5 #8. 1 and 7 and 6 2.2. study selection epidemiological studies conducted on the iranian population with tsci were included, and those conducted on individuals with non-traumatic spinal cord injuries, with irrelevant outcomes, case series, case reports, and the letters to the editor were excluded. 2.3. data extraction and quality assessment the methodological quality of included studies was assessed using robins-i tool (23). two authors extracted the epidemiological and demographic data, independently, using the same extraction form. the extracted information included 1) study characteristics (first author, year, place, period, and type), demographic characteristics (sample size, mean age, and sex), and epidemiological outcomes (prevathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e80 table 1: characteristics of included studies study province period n ratio (m:f) mean age incidence /1000000 prevalence /10000 leading causes second causes andalib, 2018 (24) guilan 2015-2018 127 3.5: 1 38.27 nr nr mvcs derakhshanrad, 2016 (25) tehran 2011-2015 1137 3.8:1 29.1 nr 2.36 mvcs falling fakharian, 2004 (27) isfahan 1995-1999 225 3.6:1 39 nr nr falling mvcs fakharian, 2019 (26) isfahan 2014-2017 986 3.3:1 39.5 nr nr mvcs falling ghajarzadeh, 2019 (28) tehran 2013-2017 830 4.3:1 29 nr nr mvcs falling haddadi, 2015 (29) mazandaran 2012-2014 906 1.3:1 nr nr nr mvcs falling jazayeri, 2015(30) tehran, alborz 2015 nr nr nr nr 2.96 nr nr kamravan, 2014 (31) fars 2009-2012 261 3:1 37.2 nr nr mvcs falling khazaeipour, 2017 (32) tehran 2012-2013 140 2.5:1 nr nr nr mvcs falling rahimi-movaghar, 2009 (35) tehran 2007-2008 4 1:1 31.7 nr 4.4 mvcs falling ramezani, 2019 (36) guilan 2015-2017 170 2.3:1 40.2 nr nr mvcs falling rasouli, 007 (33) southeastern iran 1994-2005 64 18:1 27.42 nr nr mvcs saatian, 2020 (37) hamadan 2007-2017 3219 2:1 41.7 nr nr mvcs falling sharif-alhoseini, 2014 (38) tehran 2010-2011 138 5.5:1 33.2 10.5 nr falling mvcs tabesh, 2018 (34) isfahan 2012-2018 510 2.3:1 42.31 nr nr mvcs falling yousefzadeh-chabok, 2010 (41) guilan 2005-2006 245 2.5:1 38.2 nr nr mvcs falling yousefzadeh-chabok, 2015 (42) guilan 2015 76 8.5:1 35.2 nr nr mvcs falling yadollahi, 2018 (39) fars 2017 171 4.9:1 38.2 nr nr mvcs falling yazdani, 2021 (40) hormozgan 2017 207 2.5:1 40.2 nr nr mvcs falling n: number of participants, m: male, f: female, nr: not reported, mvcs: motor vehicle collisions. table 2: risk of bias (robins-i) study confounding selection intervention measurement missing data outcome measurement reported result overall andalib, 2018 moderate low low low low moderate moderate derakhshanrad, 2016 moderate low low low low moderate moderate fakharian, 2004 moderate low low low low moderate moderate fakharian, 2019 moderate low low low low moderate moderate ghajarzadeh, 2019 moderate low low low low moderate moderate haddadi, 2015 moderate low low low low moderate moderate jazayeri, 2015 moderate low low low low moderate moderate kamravan, 2014 moderate low low low low moderate moderate khazaeipour, 2017 moderate low low low low moderate moderate rahimi-movaghar, 2009 moderate low low low low moderate moderate ramezani, 2019 moderate low low low low moderate moderate rasouli, 2007 moderate low low low low moderate moderate saatian, 2020 moderate low low low low moderate moderate sharif-alhoseini, 2014 moderate low low low low moderate moderate tabesh, 2018 moderate low low low low moderate moderate yousefzadeh-chabok, 2010 moderate low low low low moderate moderate yousefzadeh-chabok, 2015 moderate low low low low moderate moderate yadollahi, 2018 moderate low low low low moderate moderate yazdani, 2021 moderate low low low low moderate moderate note: moderate=the study is sound for a non-randomized study with regard to this domain but cannot be considered comparable to a well-performed randomized trial; low=the study is comparable to a well-performed randomized trial with regard to this domain. lence and incidence rate, risk factors, level of injuries, and mortality rate). 2.4. evidence synthesis the epidemiological and demographic findings of included studies were summarized. the comprehensive metaanalysis software was used to analyze the data. the mean difference (md) and the risk ratio (rr) with a 95% confidence this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. saheban maleki et al. 4 interval (ci) were used for continuous and dichotomous variables, respectively. the random-effect model was used for studies with i2>50% or p <0.1. otherwise, the fixed-effect model was used. 3. results 3.1. search results prisma flow diagram of the study selection process is shown in figure 1. in total, 265 records were identified after duplicate removal by searching the databases and resources. after screening the records by their titles and abstracts, 36 studies were screened for eligibility. finally, nineteen studies (24-42) involving 9416 cases were included in our analysis. the main characteristics of the included studies are presented in table 1. 3.2. assessment of risk of bias the results of assessing risk of bias of included studies are presented in table 2. the methodological quality of included studies was acceptable. 3.3. demographic characteristics the included studies reported the mean age of tsci patients in the range of 27.42 to 42.31 years. the pooled mean age of the participants was 35.80 ± 1.07 (ci: 33.69 to 37.91) years. a small number of studies reported the frequency of tsci by age groups. according to the findings of the studies, the largest age group was under 30 years. the majority of participants were male (69%; 95% ci: 68% to 70%) and the maleto-female ratio was 2.4:1. the lowest and highest male-tofemale ratios were 1.3:1 and 18:1 in the north and south-east of iran, respectively. 3.4. etiology mvcs were the leading cause of tsci in iran (57.9%; ci: 25% to 63%), followed by falls (32 %; ci: 26% to 38%), assaults (7%; ci: 3% to 14%), and other causes (8% ci: 6% to 11%), respectively ((figure 2). however, in two studies (27, 38), falls were presented as the main cause of tsci. 3.5. prevalence and incidence three studies (25, 30, 35) reported the prevalence of tsci in the iranian population. the meta-analysis result showed the prevalence of tsci in the iranian population was 4.4 per 10000 people (figure 3). only one study (38) examined the incidence of tsci, according to which the incidence rate of tsci among the iranian population was estimated at around 10.5 per million people. 3.6. mortality rate nine studies involving 6744 cases reported the mortality rate among people with tsci. the findings of meta-analysis revealed that mortality rate due to tsci was 3.9 % (95% ci: 0.02 to 0.06; p<0.05) (figure 4). 3.7. injury level anatomical most common sites of tsci were thoracolumbar (27%; ci: 10% to 55%), cervical (23%; ci: 16% to 31%), thoracic (20%; ci: 9% to 40%), lumbar (20%; ci: 12% to 31%), and other multiple traumas (16%; ci: 7% to 32%), respectively (figure 5). 3.8. sensitivity analysis a sensitivity analysis was performed to compare the fixedand random-effect estimates of the effect size. the result showed no change in the effect size. 4. discussion according to the present study’s findings, the overall mean age of tsci in the iranian population was 35.80 ± 1.07 years. the results of a systematic review conducted in the middle east and north africa showed that the mean age of the patients with tsci was 31.32 years (43), which was similar to our finding. in addition, the most commonly affected people were in the 20-29 years age group (43). this result is also in line with our findings. a systematic review of the epidemiology of tsci in asian countries indicated that the mean age of injured people ranged from 26.8 to 56.6 years (44). our study also revealed that most tscis (69%) occurred in males, and tsci rate in men was almost 2.4 times greater than women. the pooled proportion of male gender in the middle east and north africa (43) was 77% of all cases, which was similar to our results. the evidence showed that in developing countries (45), males comprised most tsci cases. furthermore, a global study showed that the majority of tsci occurred in males and mostly in individuals aged under 30 years (9). our study demonstrated that mvcs were the leading cause of tsci in iran. a similar pattern was found in the middle east and north africa regions (43), in which mvcs were introduced as the main cause of injuries, followed by falls. moreover, a systematic review (45) conducted in developing countries showed that mvcs and falls were the most common mechanisms of tsci. similar findings were observed in asia (44) and around the world (9), which were in line with our results. however, in europe, the most common causes of injuries were falls and mvcs, respectively (46). the incidence and prevalence of tsci varied between developing and developed countries (9). based on the present study, the prevalence of tsci in iran was 4.4 per 10000 people, and the incidence rate of tsci among the iranian poputhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e80 lation was estimated at 10.5 per million people. the pooled annual incidence of tsci in the middle east and north africa (43) was 23.24 per million people, which was higher than that of iran. according to the meta-analysis, the mortality rate due to tsci among the iranian population was 3.9%. a metaanalysis (4) conducted by chamberlain et al. showed that tsci-related mortality rates ranged from 2.1%, 7.0%, 7.6%, to 24.1% in the who regions of western pacific, europe, the americas, and africa, respectively. the result of research conducted in europe (46) showed that most deaths occurred in the older age groups, especially in the female population. the most common causes of death were falls (53%) and mvcs (23%) with the same proportions in both sexes. generally, older age, injuries related to tsci, tetraplegia, and tracheostomy have been suggested as the risk factors associated with mortality due to tsci (47, 48). since environmental, behavioral, and health factors can play a key role in mortality after tsci (49), intervention strategies focusing on these factors may lead to reduction in mortality due to tsci (50). based on the findings of the current study regarding injury levels, most participants had thoracolumbar cord and cervical injuries. a literature review of worldwide epidemiology (51) showed that cervical level of the spine was the most common part to get injured. it seems that appropriate prevention and control strategists for tsci in iran should focus on males, mvcs, and the age group under 30 years. these findings can be helpful for health researchers and policymakers to plan strategies for controlling and preventing these injuries. however, further detailed studies with large sample sizes and subgroup data are required to investigate the factors affecting tsci in iran. 5. limitations this study had some limitations. first, not all studies in the meta-analysis reported the outcomes of interest, including standard deviation of mean age, male to female ratio, injury mechanisms, and injury levels. second, most studies have been conducted in the central part of iran, which can be considered as a problem for the generalizability of our findings. finally, we could not perform a meta-analysis on tsci-related mortality rates based on injury mechanisms, age groups, and sex due to lack of data. 6. conclusion based on the findings of this meta-analysis, the pooled incidence and prevalence of tsci in the iranian population was 10.5/1000.000 people and 4.4/10.000 people, respectively. tscis had occurred more frequently in males following mvcs, and in the age group under 30 years. the pooled mortality rate due to tsci was 3.9% (95% ci: 0.02 to 0.06; p<0.05). 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions study design: roya amiri, mohsen saheban maleki designing search strategy and performing the search: seyedeh omolbanin seyedrezaei, mohsen saheban maleki, farahnaz khajehnasiri data gathering: maryam ebrahimpour roodposhti, hesamedin askari majdabadi analysis and interpreting the result: behzad khedri, mohsen poursadeqiyan, nasir amanat drafting the manuscript: roya amiri, farahnaz khajehnasiri critical review of the paper: all authors all authors approved the final manuscript version and are accountable for all work aspects. 7.3. funding source none. 7.4. conflict of interest there is no conflict of interest. references 1. sabapathy v, tharion g, kumar s. cell therapy augments functional recovery subsequent to spinal cord injury under experimental conditions. stem cells int. 2015; 1-12. 2. davari m, amani b, amani b, khanijahani a, akbarzadeh a, shabestan r. pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis. korean j pain. 2020;33(1):3-12. 3. van den berg m, castellote j, mahillo-fernandez i, de pedro-cuesta j. incidence of spinal cord injury worldwide: a systematic review. neuroepidemiology. 2010;34(3):184-92. 4. 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m, et al. epidemiology of traumatic spinal cord injury in developing countries: a systematic review. neuroepidemiology. 2013;41(2):65-85. 46. majdan m, plancikova d, nemcovska e, krajcovicova l, brazinova a, rusnak m. mortality due to traumatic spinal cord injuries in europe: a cross-sectional and pooled analysis of population-wide data from 22 countries. scand j trauma resusc emerg med. 2017;25(1):110. 47. chhabra hs, sharawat r, vishwakarma g. in-hospital mortality in people with complete acute traumatic spinal cord injury at a tertiary care center in india—a retrospective analysis. spinal cord. 2022;60(3):210-5. 48. higashi t, eguchi h, wakayama y, sumi m, saito t. risk factors associated with mortality after traumatic cervical spinal cord injury. ota int. 2018;1(1): 1-4. 49. cao y, krause j, dipiro n. risk factors for mortality after spinal cord injury in the usa. spinal cord. 2013;51(5):413-8. 50. krause js, cao y, devivo mj, dipiro nd. risk and protective factors for cause-specific mortality after spinal cord injury. arch phys med rehabil. 2016;97(10):1669-78. 51. kang y, ding h, zhou h, wei z, liu l, pan d, et al. epidemiology of worldwide spinal cord injury: a literature review. j neurorestoratology. 2018;6(1):1-9. 52. ahuja cs, wilson jr, nori s, kotter m, druschel c, curt a, et al. traumatic spinal cord injury. nat rev dis primers. 2017;3(1):1-21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. saheban maleki et al. 8 figure 1: the prisma flow diagram of study selection process. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e80 figure 2: forest plot of mechanism of injury: motor vehicle collisions (a), falls (b), assault (c), other causes (d). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. saheban maleki et al. 10 figure 3: forest plot of prevalence rate of traumatic spinal cord injuries. figure 4: forest plot of rate of mortality due to traumatic spinal cord injuries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e80 figure 5: forest plot of the level of the injury: cervical (a), thoracic (b), thoracolumbar (c), lumbar (d), multiple traumas (e). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2017; 5 (1): e47 ca s e re p o rt recurrent syncope following substance abuse; a case report forod salehi1, mohammad mehdi hassanzadeh taheri2, hamidreza riasi3, omid mehrpour4,5∗ 1. department of pediatric, birjand university of medical sciences, birjand, iran. 2. department of anatomical sciences, faculty of medicine, birjand university of medical sciences, birjand, iran. 3. neurology department, birjand university of medical sciences, birjand, iran. 4. atherosclerosis and coronary artery research center, birjand university of medical sciences, birjand, iran. 5. medical toxicology and drug abuse research center, birjand university of medical sciences, birjand, iran. received: may 2016; accepted: july 2016; published online: 14 january 2017 abstract: drug abuse is considered as the most common poisoning in the world. stimulants agent especially amphetamines and methamphetamines are among important abused substances. different types of neurologic, psychiatric, respiratory, gastrointestinal, and cardiogenic complications have been reported to be related to methamphetamine consumption. some of these substances could cause dysrhythmias which is the most prevalent etiology of cardiogenic syncope. ecstasy, as one of the most commonly abused drugs, is known as a cause of cardiac dysrhythmias. here we report a young boy who was admitted into the emergency department following three syncope attacks. all cardiac and neurologic assessments were normal; and finally ecstasy abuse was detected as the main etiology of syncopes. keywords: substance-related disorders; syncope; amphetamine; n-methyl-3,4-methylenedioxyamphetamine; case report © copyright (2017) shahid beheshti university of medical sciences cite this article as: salehi f, hassanzadeh taheri m, riasi h, mehrpour o. recurrent syncope following substance abuse; a case report. emergency. 2017; 5 (1): e47. 1. introduction drug abuse is considered as the most common poisoning in the world and about 2 to 5 million of such poisoning occur annually in the united states (1). stimulants agent especially amphetamines and methamphetamines are among important abused substances (2). different types of neurologic, psychiatric, respiratory, gastrointestinal, and cardiogenic complications have been reported to be related to methamphetamine consumption (3-7). some of these substances could cause dysrhythmias which is the most prevalent etiology of cardiogenic syncope (8). to emphasize the importance of this topic, here we report a case of recurrent syncope following amphetamine abuse. ∗corresponding author: omid mehrpour; medical toxicology and drug abuse research center, birjand university of medical sciences, moallem avenue, birjand, iran. tel: +985632381270; email: omehrpour@yahoo.com.au 2. case presentation: an 18-year-old boy was admitted to the emergency department of markaze–tebi–koodakan hospital, tehran, iran with chief complaint of sudden weakness, transient loss of consciousness and falling down at home. a meticulous history of the patient revealed 2 similar attacks in last 3 months. further evaluations in previous attacks including brain imaging, cardiac stress test were all negative and genetic testing revealed no evidence of channelopathies. there was no history of head trauma, cardiac disease or regular medication use. the patient denied any substance abuse and family history revealed no sudden cardiac death. the patient’s vital signs on admission were stable, neurological and cardiac examinations were normal. his glasgow coma score (gcs) was 15/15, pupils responded normally to light, deep tendon reflex (dtr) and cranial nerves examinations did not revealed any abnormality. electrolytes, blood sugar level, and thyroid function tests were performed and all were reported in normal range. the patient’s electrocardiogram (ecg) on arrival was normal. echocardiographic evaluation showed no this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. salehi et al. 2 figure 1: 24 hours cardiac holter monitoring. a uniform, sustained ventricular tachycardia. structural heart disease. brain magnetic resonance imaging (mri) and electroencephalography (eeg) were normal and the tilt test result was negative. twenty-four hour cardiac holter monitoring was performed in which a uniform, sustained ventricular tachycardia (vt) was revealed (figure 1). psychiatric consultation was carried out due to poor family support and chaotic family interactions. psychiatric consultation revealed that the patient had two previous suicide attempts and history of ecstasy abuse. based on history, he had used ecstasy a night before, thereby resulting in syncope attacks. an evaluation of serum toxins level revealed a methamphetamine serum level of 12 mg/dl. the patient was discharged with a diagnosis of syncope caused by vt due to methamphetamine abuse. psychiatric follow-up was advised for 6 months. during this period, ecstasy usage was discontinued and he did not experience any episode of syncope attacks. 3. discussion: although, intoxication and their complications are usually associated with overdose consumption of abuse drugs, but the use of actual dose of amphetamine may lead to cardiovascular events (9). palpitation, premature ventricular and supraventricular contraction, accelerated atrioventricular conduction, atrioventricular block, bundle branch block, supraventricular tachycardia, ventricular tachycardia and fibrillation are among the most prevalent cardiogenic complications (10). in a study by fabrizio et al. it was shown that methylenedioymethamphetamine (mdma) induces arrhythmia through the release of serotonin and catecholamine (especially noradrenaline), which are responsible for most severe accidents in the cardiovascular system (4). elevated catecholamine level causes tachycardia and hypertension that lead to increased oxygen demand and vasospasm. myocardial ischemia occurs in response to decreasing oxygen supply and increasing oxygen demand in the myocardium that leads to increasing the potential risk of cardiac arrhythmia (11). zhuo et al. demonstrated the mechanism of reduction of connexin 43 and n-cadherin (myocardial gap junction proteins) in the pathophysiology of cardiovascular arrhythmia due to mdma exposure. mdma reduces both connex in 43 and n-cadherin. these forms of proteins are multiprotein complexes that could allow the assemblage of both gap and fascia adherens junctions. loss or decreased gap junction-proteins may disrupt cardiac impulse propagation and result in ventricular arrhythmia (12). after cannabis, methamphetamines and their compounds have become the most widely abused illicit drugs all over the world (8, 13). ecstasy is an easily available drug and used mainly by young individuals in parties. this case study presents a young man with recurrent syncope further diagnosed as ecstasy abuse as the main cause. in syncope with unknown etiology, history of the patient must be suspected and accurately examined. 4. appendix 4.1. acknowledgements the author thanks dr. toba kazemi, for editing this manuscript. 4.2. author’s contribution f.s managed the patient. h.m and m ht followed the patient and wrote the draft. om completed, revised and approved the article. 4.3. conflict of interest the authors declare that there is no conflict of interest. 4.4. funding none. references 1. litovitz tl, klein-schwartz w, rodgers gc, cobaugh dj, youniss j, omslaer jc, et al. 2001 annual report of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e47 american association of poison control centers toxic exposure surveillance system. the american journal of emergency medicine. 2002;20(5):391-452. 2. mehrpour o. methamphetamin abuse a new concern in iran. daru journal of pharmaceutical sciences. 2012;20(1):1. 3. albertson te, derlet rw, van hoozen be. methamphetamine and the expanding complications of amphetamines. western journal of medicine. 1999;170(4):214. 4. schifano f. a bitter pill. overview of ecstasy (mdma, mda) related fatalities. psychopharmacology. 2004;173(3-4):242-8. 5. lewis da, dhala a. syncope in the pediatric patient: the cardiologist’s perspective. pediatric clinics of north america. 1999;46(2):205-19. 6. liechti me, kunz i, kupferschmidt h. acute medical problems due to ecstasy use. case-series of emergency department visits. swiss medical weekly. 2005;135(4344):652-7. 7. al shehri ma, youssef aa. acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines. journal of the saudi heart association. 2015. 8. wijetunga m, seto t, lindsay j, schatz i. crystal methamphetamine-associated cardiomyopathy: tip of the iceberg? journal of toxicology: clinical toxicology. 2003;41(7):981-6. 9. olfson m, huang c, gerhard t, winterstein ag, crystal s, allison pd, et al. stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. journal of the american academy of child & adolescent psychiatry. 2012;51(2):147-56. 10. vearrier d, greenberg mi, miller sn, okaneku jt, haggerty da. methamphetamine: history, pathophysiology, adverse health effects, current trends, and hazards associated with the clandestine manufacture of methamphetamine. disease-a-month. 2012;58(2):38-89. 11. karlovsek mz, alibegovic a, balazic j. our experiences with fatal ecstasy abuse (two case reports). forensic science international. 2005;147:s77-s80. 12. zhuo l, liu q, liu l, sun t-y, wang r-s, qu g-q, et al. roles of 3, 4-methylenedioxymethamphetamine (mdma)-induced alteration of connexin43 and intracellular ca 2+ oscillation in its cardiotoxicity. toxicology. 2013;310:61-72. 13. won s, hong ra, shohet rv, seto tb, parikh ni. methamphetamine-associated cardiomyopathy. clinical cardiology. 2013;36(12):737-42. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion: appendix references emergency. 2016; 4 (3): 159-162 br i e f re p o rt focal myopericarditis as a rare but important differential diagnosis of myocardial infarction; a case series younes nozari1, masih tajdini1∗, mehdi mehrani1, rosa ghaderpanah 1 1. tehran heart center, tehran university of medical sciences, tehran, iran. received: january 2016; accepted: march 2016 abstract: distinguishing st-elevation myocardial infarction (stemi) differential diagnoses is more challenging. myopericarditis is one of these differentials that results from viral involvement of myocardium and pericardium. myopericarditis in focal form can mimic electrocardiogram (ecg) features of acute stemi and elevate cardiac enzymes. myocarditis patients may face thrombolytic related complications such as intracranial bleeding, myocardial rupture, and hemorrhagic cardiac tamponade. furthermore, re-administration of streptokinase (a common thrombolytic agent in our country) is banned for at least six months of previous administration; however, it can save patients lives in emergency conditions such as massive pulmonary embolism. it seems that, when dealing with a young patient presenting to emergency department with acute chest pain and st segment elevation on ecg, we should consider focal myocarditis as an important but rare differential diagnosis of stemi. in this report, we describe three cases of focal myocarditis, primarily misdiagnosed as stemi. keywords: coronary angiography; electrocardiography; myocardial infarction; myocarditis; emergency medicine © copyright (2016) shahid beheshti university of medical sciences cite this article as: nozari y, tajdini m, mehrani m, ghaderpanah r. focal myopericarditis as a rare but important differential diagnosis of myocardial infarction; a case series. emergency. 2016; 4 (3): 159-162. 1. introduction determining the necessity and timing of urgent revascularization are important matters in patients who present with chest pain accompanied by st segment elevation and possible myocardial infarction. distinguishing differential diagnoses of st-elevation myocardial infarction (stemi) is even more challenging. myopericarditis is one of these differentials that results from viral involvement of myocardium and pericardium of the heart. pleuritic chest pain, fatigue and decreased exercise capacity with history of a febrile syndrome are its common manifestations (1). myopericarditis in focal form can mimic acute stemi in its electrocardiogram (ecg) features and elevated cardiac enzymes (2). endomyocardial biopsy (emb) with the histological dallas criteria is the gold standard for diagnosing myocarditis. however, when we have focal involvement, emb is limited by high variability and sampling error (3, 4). recently, cardiac magnetic resonance (cmr) with gadolinium has been introduced ∗corresponding author: masih tajdini; tehran heart center, tehran university of medical sciences, tehran, iran. tel: 00989125645406 / fax: 00982188029731; email: drmasih84@yahoo.com as an accurate technique to differentiate acute myocarditis from acute myocardial infarction (5, 6). myocarditis patients may face thrombolytic related complications such as intracranial bleeding, myocardial rupture, and hemorrhagic cardiac tamponade. furthermore, re-administration of streptokinase (a common thrombolytic agent in our country) is banned for at least six months of previous administration; however, it can save patients lives in emergency conditions such as massive pulmonary embolism, ischemic stroke and stemi (7, 8). in this report, we describe three cases of focal myocarditis, primarily misdiagnosed as stemi. 2. case presentation all three cases reported in this series are young patients presented to emergency department following 2-3 hours of constant severe retrosternal chest pain and ecg findings in favor of stemi. table 1 summarizes clinical and diagnostic findings of patients and figure 1 shows 12 leads ecgs of cases. all three patients were sent to catheterization laboratory and were diagnosed with focal myocarditis, based on collective evidence. patients were treated with 600 mg ibuprofen three times a day along with 0.5 mg colchicine twice daily for two this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com y. nozari et al. 160 figure 1: 12-leads electrocardiogram of reported patients. weeks. abnormal ecg findings were reversed after three days of treatment. ejection fractions of patients at one-month follow up echocardiography were 50-55%, 50%, and 50% for cases 1 3, respectively. no evidence of regional wall motion abnormality was detected on one-month follow up echocardiography of the studied patients. for all of these patients, secondary causes of myopericarditis were assessed. all serologic markers were in normal range. 3. discussion chest pain accompanied by elevated cardiac enzymes and normal coronary arteries are in favor of myocarditis diagnosis. although, our patients were young and had history of preceding viral illness, stsegment elevation, which supports involvement of one vessel territory, raised the possibility of an acute coronary syndrome. myocarditis is caused by diffuse inflammatory process of immune system in response to an etiologic factor. the etiologic factor is usually one of the following: infectious, post viral autoimmune-related, autoimmune-mediated (lupus myocarditis, giant-cell myocarditis [gcm]) or drug-associated (hypersensitivity myocarditis, toxic myocarditis). overlap of virus-mediated damage, inflammation and autoimmune dysregulation leads to myocardial injury and necrosis. thus, in generalized form of myocarditis, left ventricular dysfunction occurs and may proceed to end stage heart failure (9). it seems that in focal myocarditis just a small section of myocardium is involved, so there is less myocardial damage and it is reversible. differential diagnosis stemi is the most important differential diagnosis of focal myocarditis. eosinophilic endomyocardial disease (loeffler syndrome) is another differential diagnosis that is characterized by extensive necrosis, mural and intravascular thrombi without pathologic or clinical myocarditis. hypersensitivity myocarditis is an important differential diagnosis that should be ruled out, because cardiac function may improve by cessation of offending drug. cardiac sarcoidosis (cs), which is characterized by the presence of epithelioid granulomas formation, should also be considered in differential diagnosis (10). emergency department management cardiac monitoring for detecting dysrhythmias is necessary for these patients. supplemental oxygen and fluid should be considered based on the patient’s condition. myocarditis with reduced ejection fraction should be approached the same as other causes of congestive heart failure (chf). sympathomimetic drugs should be avoided due to their role in increasing the extent of myocardial necrosis and mortality. in addition, beta-blockers should not be administered in the acutely decompensated phase of illness. temporary pacemaker placement is required in symptomatic high degree atrioventricular blocks but very few patients may need permanent pacer or implantable cardioverter defibrillator (icd) placement (11). diagnostic approach definitive diagnosis can be confirmed by different techniques. endomyocardial biopsy is the gold standard method with high specificity and low sensitivity. however, complications such as myocardial perforation and death have been reported. in focal myocarditis, myocardial biopsy is not so helpful because the involvement is local and biopsy may be taken from the unaffected part (7, 8). edema and myocyte inflammation can be detected by cardiac magnetic resonance imaging (mri). unlike mi, in which subendocardial enhancement is the characteristic finding, in myocarditis enhancement is originated from epicardium with subendocardial sparing. in a study, biopsy specimens taken from areas of gadolinium enhancement had myocarditis features on pathologic findings in 90% of cases (4, 5). in addition, cardiac computed tomography (ct) scan can be used for diagnosis. recent studies showed that findings were similar between cardiac ct and mri. considering that ct has some superiority in comparison to mri, including feasibility of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 161 emergency. 2016; 4 (3): 161-162 table 1: clinical and diagnostic findings of studied patients findings case 1 case 2 case 3 age (years) 41 20 26 sex male male female cardiac risk factor cigarette smoker negative cigarette smoker history of febrile disease uri 2 weeks ago uri 4 days ago negative physical examination normal normal normal vital signs systolic bp (mmhg) 110 diastolic bp (mmhg) 70 pulse rate / minute 90 respiratory rate / minute 24 temperature (c) 37 electrocardiographic st elevation π, iπ, avf i, avl π, iπ, avf st depression i, avl iπ, avf avl echocardiographic wall motion abnormality base and mid-inferior posterior no ejection fraction (%) 45 35-40 50 hs-ctnt (pg/ml)# baseline 450 83 177 3 hours later 711 1026 1395 angiography normal normal normal *normal range: < 14 pg/ml. #hs-ctnt: high-sensitive cardiac troponin t. uri:upper respiratory tract infection. coronary artery anatomy investigation, better evaluation of myocardial inflammation and lower costs (11, 12). speckle tracking echocardiogram (ste) is a precise method for evaluation of myocarditis patients. in a study, strain (s) and strain rate (sr) imaging were compared in acute myocarditis patients with preserved left ventricular ejection fraction. septal thickness, left ventricular end-systolic dimension (lvesd), and ejection fraction were different between them. therefore, this technique helps us thoroughly evaluate patients who initially present with acute myocarditis (13). in addition to cardiac injury markers, the level of brain natriuretic peptide (bnp) can also be measured. prognosis in contrast to generalized myocarditis that can proceed to congestive heart failure and death due to arrhythmia or severe left ventricular dysfunction, it seems that prognosis is better in focal form (14-16). high concentrations of bnp are correlated with poor prognosis in patients with myocarditis (14). 4. conclusion when dealing with a young patient presenting to emergency department with acute chest pain and st segment elevation on ecg, we should consider focal myocarditis as an important but rare differential diagnosis of stemi. 5. appendix 5.1. acknowledgements we express our thanks to all staff at tehran heart center for their help and assistance in management of these cases. 5.2. conflict of interest none declared. 5.3. funding support none declared. 5.4. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. tajdini m. spontaneous myopericarditis in a patient under dexamethasone: a double-edged sword? journal of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com y. nozari et al. 162 the saudi heart association. 2015;27(4):292-4. 2. testani jm, kolansky dm, litt h, gerstenfeld ep. focal myocarditis mimicking acute st-elevation myocardial infarction. texas heart institute journal. 2006;33(2). 3. chow lh, radio sj, sears td, mcmanus bm. insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. journal of the american college of cardiology. 1989;14(4):915-20. 4. deckers jw, hare jm, baughman kl. complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center. journal of the american college of cardiology. 1992;19(1):43-7. 5. gahide g, bertrand d, roubille f, tron c, skaik s, piot c, et al. mr delayed enhancement imaging findings in suspected acute myocarditis. european radiology. 2010;20(1):65-72. 6. mahrholdt h, wagner a, judd rm, sechtem u, kim rj. delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. european heart journal. 2005;26(15):1461-74. 7. ohman em, topol ej, califf rm, bates er, ellis sg, kereiakes dj, et al. an analysis of the cause of early mortality after administration of thrombolytic therapy. coronary artery disease. 1993;4(11):957-64. 8. califf rm, fortin df, tenaglia an, sane dc. clinical risks of thrombolytic therapy. the american journal of cardiology. 1992;69(2):a12-a20. 9. dennert r, crijns hj, heymans s. acute viral myocarditis. european heart journal. 2008. 10. schultz jc, hilliard aa, cooper lt, rihal cs, editors. diagnosis and treatment of viral myocarditis. mayo clinic proceedings; 2009: elsevier. 11. brady wj, ferguson jd, ullman ea, perron ad. myocarditis: emergency department recognition and management. emergency medicine clinics of north america. 2004;22(4):865-85. 12. mahrholdt h, goedecke c, wagner a, meinhardt g, athanasiadis a, vogelsberg h, et al. cardiovascular magnetic resonance assessment of human myocarditis a comparison to histology and molecular pathology. circulation. 2004;109(10):1250-8. 13. axsom k, lin f, weinsaft jw, min jk. evaluation of myocarditis with delayed-enhancement computed tomography. journal of cardiovascular computed tomography. 2009;3(6):409-11. 14. hsiao j-f, bonnichsen cr, koshino y, saleh hk, yu y, pellikka pa, et al. left ventricular deformation by 2-d speckle tracking echocardiogram for the diagnosis of acute myocarditis with preserved lv ejection fraction. circulation. 2010;122(21 supplement):a20570. 15. zhang c, shen d, sun h, zhang l, ma y, huang d. [prognostic value of brain natriuretic peptide in people with viral myocarditis]. zhonghua shi yan he lin chuang bing du xue za zhi= zhonghua shiyan he linchuang bingduxue zazhi= chinese journal of experimental and clinical virology. 2012;26(2):125-6. 16. caforio al, pankuweit s, arbustini e, basso c, gimenoblanes j, felix sb, et al. current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the european society of cardiology working group on myocardial and pericardial diseases. european heart journal. 2013;34(33):263648. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 45 emergency 2015; 3 (1): 45-47 case report rupture of hydatid liver cyst into peritoneal cavity following blunt abdominal trauma; a case report narges kalantari1, 2, masomeh bayani3*, mina abbas-zadeh3 1. cellular and molecular biology research center, babol university of medical sciences, babol, iran. 2. department of laboratory sciences, faculty of paramedical sciences, babol university of medical sciences, babol, iran. 3. infectious disease and tropical medicine research center, babol university of medical sciences, babol, iran. *corresponding author: bayani masomeh; infectious disease and tropical medicine research center, ganjafrouz avenue, babol university of medical sciences, babol city, mazandaran province, iran. tel/fax: +98 11 32238284; email: m_baiany@yahoo.com; received: august 2014; accepted: september 2014 abstract hydatid cyst is a serious parasitic infection in places, which people has a close contact with dogs or sheep. they may be found as an incidental findings during routine clinical examination or even followed by radiographic or ultrasonography evaluation. the disease becomes more complicated if rupture of the cysts occurs due to blunt trauma or spontaneously increases of intra-cystic pressure. here, we reported a case of hydatid liver cyst that ruptured into the peritoneal cavity after blunt abdominal trauma. key words: hydatid cyst; echinococcosis, hepatic; wounds, nonpenetrating; rupture; anaphylaxis cite this article as: kalantari n, bayani m, abbas-zadeh m. rupture of hydatid liver cyst into peritoneal cavity following blunt abdominal trauma; a case report. emergency. 2015;3(1):45-7. introduction: hydatid cyst is a serious parasitic infection in places which people has a close contact with dogs or sheep (1). mehmet yilmaz and et al. mentioned that these cysts ordinary have a chronic, latent, and asymptomatic course which are developed more frequently in liver (50%–77%) and lungs (18%–35%), while may be formed in other organs. they may be found as an incidental findings during routine clinical examination or even followed by radiographic or ultrasonography (us) evaluation (2). the disease becomes more complicated if rupture of the cysts occurs due to blunt trauma or spontaneously increases of intra-cystic pressure (3-6). hydatid cysts may be directly ruptured into the peritoneal cavity or via the diaphragm into the pleural cavity. ruptures can also occur into the hollow viscous or even biliary tract (7). however, hydatid cyst rupture requires proper treatment consists of emergency surgery and also special postoperative care. here, we reported a case of hydatid liver cyst (hlc) that ruptured into the peritoneal cavity after blunt abdominal trauma. case presentation: a 17-year-old man referred to the emergency department after falling from motorcycle. he also complained from abdominal pain and vomiting. he was admitted just 30 minutes following the accident. his blood pressure was 100/60 mmhg, heart rate of 80 per minute, respiratory rate 23 breath per minute and axillary temperature of 37.2 ºc, and oxygen saturation of 96% on room air. on physical examination (pe) only right upper abdominal pain and rebound tenderness were observed. pe on other organs did not reveal any positive findings. chest and abdominal x-ray were normal. initial blood investigation showed leukocytosis (15700/mm3) and other indexes were normal. twenty minutes after admission, a diffuse urticarial rash on the whole body, mainly on his face and trunk, and generalized tenderness were noted. the patient received oxygen, intravenous fluid (ringer and dexter an -saline serum) in addition to intravenous steroids (hydrocortisone 200mg) and antihistamines (chlorpheniramine 20mg) as the supportive treatment. focused abdominal sonography for trauma (fast) of his abdomen demonstrated on the presence of free fluid noted in all abdominal quadrants, especially in the morison pouch (figure 1). also by using ultrasonography a large hyperechogenic area with local cystic (40 mm diameter) in the right lobe of the liver was showed. based on the above information a diagnostic laparotomy was performed. laparotomy revealed a ruptured cystic mass within the right lobe of the liver and yellow fluid containing daughter cysts and liver laceration. the cyst was removed by an open right partial hepatectomy, the peritoneal cavity washed out with hypertonic saline, and a tube drain placed in right the sub-hepatic space. he was managed in intensive care unit (icu) and received oral albendazole 15mg/kg/day. the drain was detached on the 7th day after operation. he was discharged ten days post-operation with a prescription of albendazole tablet 15mg/kg/day in divided dose for six months. he was followed up on 6th and 12th months post operation. he this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 46 kalantari et al was kept well and control trans-abdominal ultrasonography demonstrated no recurrences of the disease. discussion: hydatid disease is presented commonly in the liver caused by ecchinococcus granulosus. this disease is endemic in sheep farming areas including the middle east and some sub-saharan countries, western europe, south and central america. hydatid cyst is also endemic in iran and is responsible for about 1% admission in surgical wards (8). twenty-four hydatid cyst operations were performed in babol, iran, from 1991 to 1996 (9). in e. granulosus life cycle, human is an accidental intermediate host considered as a dead end host. generally, the disease in most cases remains silent for many years but it becomes problematic when it getting large enough or ruptured. rupture into the peritoneal cavity can be accompanied by abdominal pain, urticaria, anaphylaxis reaction, and sometimes sudden death (2). ruptures occur spontaneously or even due to trauma which causes severe clinic presentation. rupture of a hydatid cyst particularly after blunt abdominal trauma has been rarely reported. based on our best knowledge, there are a few reports on rupture of hydatid cyst after blunt trauma in iran. for example, a ruptured hydatid cyst was reported in 23-year-old man who was presented to the emergency unit after blunt trauma to his abdomen. he had abdominal pain, vomiting, and nausea with generalized itching without urticaria rash (10). hossinian and colleagues reported a giant cardiac hydatid cyst, which ruptured left ventricular free wall in a 24-year-old man admitted to the department of cardiothoracic. he complained of chest pain which started suddenly and became progressively intense during the time in addition to periodic thoracic pains during regular activities in the past 6 months (11). transabdominal ultrasonography is a very sensitive method to demonstrate the hydatid cyst rupture (12). however, primary suspicions of intra-peritoneal ruptured hydatid cyst obtained by clinical manifestation and transabdominal ultrasonography was further confirmed by laparotomy. the main method in the treatment of hydatidosis is surgery classified to radical and non-radical (conservative) methods. each method has some advantages and disadvantages and there is no information about the most efficient surgical approach in intra-peritoneal perforation of hydatid cysts. but some authors mentioned that conservative methods may have satisfactory results in an emergency situation. however, choosing of a surgical method depends on patient’s condition and preference of the surgeon (13). recurrence is an important risk in hydatidosis and may occur frequently after treatment of ruptured hydatid cysts; therefore, all patients should be followed-up carefully in postoperative period (4). intra-peritoneal rupture of hydatid cysts should be considered in the differential diagnosis of acute abdominal pain with vomiting and urticarial rash in the endemic areas. clinicians working at the emergency department should be alert regarding the rupture of hydatid cyst in the patients with acute post traumatic peritonitis and its related signs and symptoms. acknowledgments: we thank to dr. shokri and all staffs at the shafa hospital, babolsar, for their help and assistance. conflict of interest: none. funding support: none. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. aydin bk, acar ma, sumer s, demir na, erkocak of, ural o. primary hydatid disease of brachialis and biceps brachii muscles: a case report. trop doct. 2014;44(1):53-5. 2. yilmaz m, akbulut s, kahraman a, yilmaz s. liver hydatid cyst rupture into the peritoneal cavity after abdominal trauma: case report and literature review. int surg. 2012;97(3):239-44. 3. tinsley b, abbara a, kadaba r, sheth h, sandhu g. spontaneous intraperitoneal rupture of a hepatic hydatid figure 1: trans-abdominal ultrasound images show a ruptured hydatid cyst. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 47 emergency 2015; 3 (1): 45-47 cyst with subsequent anaphylaxis: a case report. case rep hepatol. 2013;2013:1-4. 4. dirican a, yilmaz m, unal b, tatli f, piskin t, kayaalp c. ruptured hydatid cysts into the peritoneum: a case series. eur j trauma emerg surg. 2010;36(4):375-9. 5. derici h, tansug t, reyhan e, bozdag ad, nazli o. acute intraperitoneal rupture of hydatid cysts. world j surg. 2006;30(10):1879-83. 6. arikanoglu z, taskesen f, aliosmanoğlu i̇, et al. spontaneous intraperitoneal rupture of a hepatic hydatid cyst. int surg. 2012;97(3):245-8. 7. erel s, kilicoglu b, kismet k, gollu a, akkus ma. peritoneal hydatid cyst perforation: a rare cause of emergency abdominal surgeries. adv ther. 2008;25(9):943-50. 8. rokni m. the present status of human helminthic diseases in iran. ann trop med parasitol. 2008;102(4):283-95. 9. ghaffari s. survey of surgery cases of hydatidosis in three educational treatment centers of babol. j babol uni med sci. 1999;1(1):27-33. 10. shahidi dadras m, gheysari m, rahimi h, lotfi s, sobhiyeh mr. pruritus after abdominal blunt trauma: early presentation of rupture of hydatid cyst. pejouhesh. 2009;33(2):123-5. [persian]. 11. hosseinian a, mohammadzadeh a, shahmohammadi g, et al. rupture of a giant cardiac hydatid cyst in the left ventricular free wall: successful surgical management of a rare entity. am j cardiovasc dis. 2013;3(2):103-6. 12. gunay k, taviloglu k, berber e, ertekin c. traumatic rupture of hydatid cysts: a 12-year experience from an endemic region. j trauma. 1999;46(1):164-7. 13. ozturk g, aydinli b, yildirgan mi, et al. posttraumatic free intraperitoneal rupture of liver cystic echinococcosis: a case series and review of literature. am j surg. 2007;194(3):313-6. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 46 emergency (2014); 2 (1): 46-47 case report atypical presentation of massive pulmonary embolism, a case report alireza majidi1, sadrollah mahmoodi2, alireza baratloo1, sahar mirbaha1* 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, baghiatollah hospital, imam hossein university, tehran, iran abstract the lack of pathognomonic signs and symptoms makes the diagnosis of pulmonary embolism (pe) difficult. here, we report a case of a 42-year-old man presented to the emergency department with worsening epigastric pain, hypotension, frank bradycardia, and final diagnosis of pe. although previous studies have indicated that abdominal pain was observed in 6.7% of patients with pe, the exact reason for abdominal pain in pe still remains unknown. tension on the sensory nerve endings, hepatic congestion, and distention of gilson’s capsule are some of the possible mechanisms of abdominal pain in pe. we conclude that emergency physicians should pay more attention to pe, which is an important differential diagnosis of shock state. in this context, rapid ultrasound in shock (rush) should be considered as a vital sign that needs to be evaluated when recording the history of patients presented to the emergency department with signs and symptoms of shock. key words: pulmonary embolism; ultrasonography; shock; abdominal pain; bradycardia cite this article as: majidi a, mahmoodi s, baratloo a, mirbaha s. atypical presentation of massive pulmonary embolism, a case report. emergency. 2014;2(1):46-7. introduction:1 he lack of pathognomonic signs and symptoms makes the diagnosis of pulmonary embolism (pe) difficult. a well-timed diagnosis and management of pe are necessary to decrease mortality. it has been reported that, annually, 50,000–200,000 deaths occur as a result of pe, with a mortality rate of 30% without treatment (1). postmortem studies have revealed that up to 70% of pes have been misdiagnosed. moreover, 40% of the dying patients had visited a clinician for ambiguous symptoms in the weeks prior to their death (1, 2). this significant amount of misdiagnosis highlights the importance of reviewing the different possible presentations of this fatal medical condition. here, we report a case of a patient presented to the emergency department (ed) with worsening epigastric pain, hypotension, frank bradycardia, and final diagnosis of pe. case report: the patient was a 42 year-old man, admitted to the ed with chief complaint of severe abdominal pain begun from the morning. the pain was sensed prominently in epigastric area with acceleration/deceleration pattern, and also crusher/vague quality that increased after eating. the pain was not positional and had neither transition nor shifting. he had no significant past medical history or previous surgery. but should mention that was *corresponding author: sahar mirbaha, resident, department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. postal code: 1989934148, phone/fax: 009822721155, email: mirsa317@yahoo.com received: 1 december 2013; accepted: 17 january 2014 addicted to methadone and was a heavy smoker (30 pack cigarettes per year) for many years. on admission to ed, he was so agitated with 28/min respiratory rate, 68/min pulse rate, 85/65 mmhg blood pressure, 88% oxygen saturation in room air, and 37°c axillary temperature. electrocardiogram (ecg) showed frank bradycardia that not matches with other vital signs (figure1). the patient was pale, had dry mucosa, presented marked epigastric tenderness on deep palpation, and had neither rebound tenderness nor guarding. the pulses in the extremities were filiform, lung examination was normal, and there were multiple red rushes (red macules) on the chest and extremity skin. focused assessment with sonography for trauma (fast) revealed mild, free fluid in morison’s pouch. with the impression of perforated hollow viscous organs, the emergency surgical consultant performed an upright chest x-ray (cxr) examination after primary resuscitation, but noted no specific finding. this examination was repeated after pushing 500 ml of air via nasogastric (ng) tube, but no specific observation could be found. double contrast abdominal and pelvic spiral computed tomography (ct) scan revealed intraperitoneal infiltration with increased intestinal wall diameter and ascites. the white blood cell count was 16200/mm3, arterial blood ph was 7.3, pco2 was 18.6 mmhg, hco3 was 11.2 meq/l, and be was −10.7. all other laboratory data, including serum amylase and lipase, urine analysis, hepatic and renal function tests, and coagulation profile were normal. during admission t mailto:mirsa317@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidi et al 47 to ed, the patient’s blood pressure was low and did not get better with fluid therapy. hence, rapid ultrasound in shock (rush) examination was performed. rush examination showed weak heart ventricles contractibility, right ventricular (rv) strain, and a clot in the apex of rv; hence, pulmonary ct angiography of the chest was immediately performed (figure 2). spiral pulmonary ct angiography showed massive emboli in the distal right pulmonary artery, hypodense clot in the right atrium with increased diameter, and also a hypodense clot in the rv apex. with the diagnosis of massive pulmonary emboli, high dose of heparin was initiated and cardiac surgery intervention was accomplished. the patient was transferred to the intensive care unit (icu), but unfortunately died. discussion: a well-timed diagnosis and management of pe are necessary with the aim of decreasing mortality. because of the lack of pathognomonic signs or symptoms, the diagnosis of pe remains vague. the classic symptoms of dyspnea, tachypnea, and decreased oxygen saturation may occur in up to 92% of cases. however, because of numerous atypical presentations, physicians must focus on other clinical features to include or exclude them as possible diagnosis. although previous studies have demonstrated that abdominal pain was observed in 6.7% of patients with pe (1, 3). the exact reason for abdominal pain in pe still remains unknown. tension on sensory nerve endings, infarctions within the microvasculature of the mesentery, hepatic congestion, distention of gilson’s capsule, or diaphragmatic pleurisy resulting from pulmonary infarction are some of the possible reasons for abdominal pain in pe, which have neither been proved nor refuted (1, 4). in contrast, syncope and bradyarrhythmia may cause parasympathetic reflex, because simultaneous slowing of the sinus rate with concomitant arteriovenous block is a common presentation of increased vagal tone. such reflex may be a mechanism for syncope in patients with pe (5). in addition, bradycardia is also a side effect of methadone hydrochloride (6). therefore, addiction to methadone, pump failure owing to massive emboli, and activation of vagal tone may explain the absence of tachycardia that we expected in our case. bedside ultrasound allows direct visualization of pathology or abnormal physiological states, and thus has become an essential and useful component in the evaluation of hypotensive patients via rush protocol, which was clearly the key point in the diagnosis of our patient (7). conclusion: pe is an important differential diagnosis of shock state, and hence, emergency physicians should pay more attention to it. in this context, rush should be considered as one of the vital signs (such as blood pressure or temperature), which needs to be evaluated when recording the history of patients presented to ed with signs and symptoms of shock. acknowledgments: the authors would like to thank the emergency ward staff for their invaluable help. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. gantner j, keffeler je, derr c. pulmonary embolism: an abdominal pain masquerader. j emerg trauma shock. 2013;6 (4):280-2. 2. stein pd, beemath a, matta f, et al. clinical characteristics of patients with acute pulmonary embolism: data from pioped ii. am j med. 2007;120(10):871-9. 3. courtney dm, kline ja. identification of prearrest clinical factors associated with outpatient fatal pulmonary embolism. acad emerg med. 2001;8(12):1136-42. 4. stein pd, terrin ml, hales ca, et al. clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. chest journal. 1991;100 (3):598-603. 5. arthur w, kaye g. the pathophysiology of common causes of syncope. postgrad med j. 2000;76(902):750-3. 6. ehret gb, desmeules ja, broers b. methadone-associated long qt syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology. expert opin on drug saf. 2007;6(3):289-303. 7. perera p, mailhot t, riley d, mandavia d. the rush exam: rapid ultrasound in shock in the evaluation of the critically lll. emerg med clin north am. 2010;28(1):29-56. figure 1: electrocardiogram of patient at the time of admission. figure 2: pulmonary computed tomography angiography of the patient.  archives of academic emergency medicine. 2023; 11(1): e57 or i g i n a l re s e a rc h associated factors of under and over-triage based on the emergency severity index; a retrospective crosssectional study thongpitak huabbangyang1, rapeeporn rojsaengroeng2∗, gawin tiyawat1, agasak silakoon1, alissara vanichkulbodee2, jiraporn sri-on2, siriwimol buathong3 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. department of emergency medicine, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. 3. phetchabun hospital, phetchabun province, thailand received: june 2023; accepted: july 2023; published online: 21 august 2023 abstract: introduction: under-triage increases patients’ risks for morbidity and mortality, whereas over-triage limits the resources available to sicker patients. this study aimed to determine the rates as well as associated factors of under-triage and over-triage in emergency department (ed), based on emergency severity index (esi) triage system. methods: in this retrospective cross-sectional study, triage level of ed patients based on the esi version 4, was studied during a 9-month period in 2019. patients’ esi level, which were examined by triage nurses were reevaluated by 3 emergency physicians and the rate of correct, under-, and over-triage as well as their associated factors were analyzed. results: 1000 cases of triage were evaluated. triage was correct in 69.1% of cases. the rate of under-triage was 4.9%, and that of overtriage was 26.0%. over-triage was significantly more common among patients aged 18–30 years than for those aged ≥65 years (adjusted odds ratio [or] = 1.73; 95% confidence interval [ci]: 1.07–2.81; p = 0.026); those with traumatic injuries (adjusted or = 1.80; 95% ci: 1.29–2.52; p = 0.001); those arriving at the hospital during the evening shift (adjusted or = 1.42; 95% ci: 1.01–2.0; p = 0.046); patients who were hospitalized (adjusted or = 0.35; 95% ci: 0.22–0.54; p < 0.001); and those with severe pain (adjusted or = 0.28; 95% ci: 0.10–0.84; p = 0.023). younger age was also significantly associated with under-triage. patients aged 18–30 years were under-triaged more often than those aged ≥65 years (adjusted or = 3.05; 95% ci: 1.16–8.00; p = 0.023). conclusion: over-triage was substantially more common than under-triage in vajira hospital. factors associated with over-triage were younger age, traumatic injury, arrival time, hospital admission, and severe pain. younger age was the only factor related to under-triage. keywords: emergency service, hospital; triage; emergency medicine; nurses; physician-nurse relations cite this article as: huabbangyang t, rojsaengroeng r, tiyawat g, silakoon a, vanichkulbodee a, sri-on j, buathong s. associated factors of under and over-triage based on the emergency severity index; a retrospective cross-sectional study. arch acad emerg med. 2023; 11(1): e57. https://doi.org/10.22037/aaem.v11i1.2076. 1. introduction triage is a main task in emergency departments (eds), performed to identify and clinically prioritize patients who have life-threatening conditions and require urgent medical service over patients with no severe conditions who are able to wait for an examination (1, 2). the ed functions around the clock, and many patients ar∗corresponding author: rapeeporn rojsaengroeng; department of emergency medicine, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. tel: +66 2-244-3000, email: rapeeporn@nmu.ac.th, orcid: https://orcid.org/0000-0002-7365-3948. rive without an appointment; queues are not used to prioritize examination and treatment (3). the numbers of patients treated at eds are likely to rise, because increasing numbers of patients have progressive diseases and are injured in accidents; however, the numbers of medical personnel and resources are typically limited, even in industrialized countries. according to research evidence, correct levels of triage help ameliorate this issue and reduce disability and mortality rates significantly (4). a recent systematic review of current and popular triage patterns in eds revealed that these patterns are based on many measures, such as the australian triage scale, canadian emergency department triage and acuity scale, manchester this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 2 triage scale, emergency severity index (esi), soterion rapid triage scale, and taiwan triage system (2). the five-level esi is currently the most popular measure for determining triage; it is used extensively worldwide, including in industrialized countries such as the united states (5), and in thailand. according to the national institute for emergency medicine in thailand, eds nationwide use version 4 of the esi. in this system, developed in 1999 in the united states, disease severity and the number of resources needed for treatment are evaluated to determine urgency. use of this screening system requires experience and expertise in triage. the task of initial triage is performed by triage nurses based on the esi in the ed (6, 7). according to a previous study, the knowledge and skills of triage nurses affected the accuracy of triage; therefore, specialized training might help increase the accuracy of triage and decrease rates of over-triage and under-triage (8). a previous large study of eds in england revealed that triage was correct in 67.8% of cases, over-triage in 28.9%, and under-triage in 3.3%. another study showed that over-triage was more common for black patients than for white patients, children were at higher risk for over-triage than were adults, and patients who used high-risk medications were at increased risk for under-triage (9). in eds in brazil, the rate of over-triage in high-acuity cases (esi level 1 or 2) was 8.7%, and in cases of moderate acuity (esi level 3) it was 13.6%; the rate of under-triage among high-acuity cases was 5.8%, and for low-acuity cases (esi level 4 or 5) it was 18.4% (10). in an ed in thailand, the accuracy of triage according to esi, performed by nurses, was 52.4% (11). in a large observational study of eds in thailand in 2016, the rate of under-triage was 34.71%, and that of over-triage was 28.35% (12). in thailand, accurate triage for patients presenting with diseases and those injured in accidents is challenging for triage nurses. the purposes of this study were to examine rate of under-triage and over-triage in an ed in thailand and to clarify factors leading to under-triage and over-triage. the findings could help improve triage according to the esi and help clinicians monitor risk factors for mistriage. 2. methods 2.1. study design and setting this retrospective, single-center, cross-sectional study was conducted in the ed of vajira hospital, navamindradhiraj university, a large tertiary care hospital in bangkok, thailand. approximately 500,000 patients visit this ed every year (13). triage is based on version 4 of the esi (6). nurses who perform initial triage have >5 years of working experience and had previous training in triage according to the esi. to maintain knowledge and skills, they annually undergo further training in triage according to the esi. this study was conducted according to the standards for the reporting of observation studies in epidemiology (strobe) statement (14) and the tenets of the 1975 declaration of helsinki and its revisions in 2000. it was approved by the institutional review board of the faculty of medicine vajira hospital, navamindradhiraj university (coa no. 93/2561), amendment 4/2023. the informed consent requirement was waived because of the retrospective nature of the study and because all patient data were anonymized. 2.2. participants the medical charts of patients who visited the ed between 1 january and 31 december 2019 were reviewed retrospectively. data were used if patients were older than 18 years, if triage was performed by triage nurses according to the esi, if triage levels were documented in medical records, and if the data could be searched in and extracted from the electronic medical record system of the hospital. patients with incomplete or missing data were not included. 2.3. data gathering in this study, triage accuracy was evaluated by two emergency physicians (eps) to finalize the triage decision. before the data were collected, interrater reliability was verified by a patient triage test. the accepted error coefficient was 20%, and the interrater reliability was analyzed using fleiss’s kappa. the principal investigator (th) randomly chose 40 medical records for the two eps (rr and gt) to compare triaging, which showed a kappa coefficient of 0.887. in a previous study, the kappa coefficient ranged from 0.81 to 1.00 (15). if the two eps disagreed about triage, a third ep (av ) was consulted to finalize triage. the principal investigator used microsoft excel to record all data, which included gender, age, comorbidities, chief complaint (injury or illness), method of transportation to ed, arrival time, chief complaints, hospital admission, critical outcomes, systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, oxygen saturation, body temperature, pain severity (based on the visual analog scale [vas]), glasgow coma scale score, capillary blood glucose concentration, and triage level. to evaluate the accuracy of triage, the eps examined each patient’s treatment data: results of blood tests, urine tests, electrocardiography, and imaging studies; administration of intravenous fluids and intravenous, intramuscular, or nebulized medication; and specialist consultation. each of these items counted as one resource. vital signs were measured during triage, and the measurements were compared between those with correct triage and those with under-, and over-triage. 2.4. outcome measures the primary objective was to study the rates of under-triage and over-triage in the ed according to the esi. the secondary this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e57 objective was to analyze factors related to under-triage and over-triage. 2.5. definitions “correct triage” was defined by a match between the triage level determined by nurses and that determined by the three eps (9, 10). “under-triage” was defined as when the first triage level determined by nurses was lower than that determined later by the eps (9, 10). “over-triage” was defined as when the first triage level determined by nurses was higher than that determined later by the eps (9, 10). triage is divided into five levels according to version 4 of the esi. esi level 1 reflects a critical emergency, such as life-threatening injury or illness; unless respiratory, cardiovascular, or neurological systems are managed immediately, the patient has a high chance of mortality, the severity of the injury or illness can increase, or complications can happen abruptly. esi level 2 reflects injury or severe illness that probably necessitates emergency treatment; without treatment, the injury or illness could become more severe or lead to complications, resulting in mortality or disability later. esi level 3 reflects no severe injury or illness, for which treatment can be delayed; affected patients can commute to the ed by themselves, but if they do not receive treatment within a certain time, the severity of injury or illness could increase, or complications could occur. esi level 4 reflects general sickness that is not an emergency, for which treatment can probably be delayed without increased severity of symptoms or later development of complications. esi level 5 reflects the need for other public health services, which do not necessitate the use of resources (6). the resource utilization checklist includes clinical laboratory studies; imaging studies; electrocardiographic monitoring; special studies; administration of fluids, parenteral medications, and intramuscular medications; and specialist consultations, as defined in the esi handbook (6). 2.6. sample size determination to explore the rates of under-triage and over-triage in the ed with regard to esi, sample size was estimated according to a formula for proportional value (16); = 0.05, and the proportional value in a referred population from a previous study was considered (10). the proportion of patients receiving under-triage and over-triage was 17% (proportional value = 16,426/96071 = 0.17); d was defined as 0.05, and the necessary sample size was therefore 217. to determine which factors led to under-triage and overtriage with regard to esi, multiple logistic regression analysis was used. the number of events per variable thus needed to be calculated (17), and the sample size needed to reflect a limited time period. according to a previous study (18), the number of events per variable could be decreased but not to fewer than 5, which meant that each predictive factor would have at least five studied outcome events. in this way, the sample size in this study could be reduced. a literature review revealed that 26 factors or variables were predictive of the level of triage selected, which reflected 130 outcome events; the rate of under-triage and over-triage in eds was calculated to be 17% (10). thus, to determine which factors led to under-triage and over-triage, the sample size needed in this study was 100 × 130/17 = 746.70. because data were retrospectively collected from medical records, an additional 20% was calculated according to a sample size adjustment formula (nnew = 746.70/[1 0.20]), which yielded 933.38. therefore, the sample size needed for this study was determined to be 1000. sampling was performed in accordance with simple random sampling among patients visiting the ed between 1 january and 31 december 2019. 2.7. statistical analysis a descriptive analysis was performed to examine variable distribution. values of continuous variables were calculated as means ± standard deviations or as medians and interquartile ranges (iqrs), and those of categorical variables were calculated as frequencies and proportions. in comparisons of two groups, differences were evaluated using independent t test or mann–whitney u test for continuous variables and using chi-square test or fisher’s exact test for categorical variables. to determine factors associated with under-triage or overtriage, multinomial logistic regression analysis was performed. ibm spss statistics for windows, version 28.0 (ibm corporation, armonk, ny, usa), was used. all statistical tests were considered statistically significant at a p level of 0.05. 3. results 3.1. baseliner characteristics of the sample of the 1000 participants triaged during the study period, 52.4% were male. the mean age was 47.94 ± 21.81 years, and the largest age group consisted of patients aged 18–30 years (29.5%). comorbidities were present in 42.7%, and 33.4% had traumatic injuries. most participants (91.5%) were walk-in patients, and 45.2% visited the hospital during the evening shift (4:00–11:59 pm). the most common chief complaint was trauma (in 25.4% of patients), followed by abdominal pain (9.9%) and fever (7.2%). the hospital admission rate was 28.7%, and 66.8% of hospitalized patients were discharged within 24 hours. table 1 summarizes the baseline characteristics of studied cases. 3.2. triage results among the triage levels determined initially, 4.3% were esi 1, 21.7% were esi 2, 59.1% were esi 3, 12.9% were esi 4, and 2% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 4 were esi 5. among the triage levels determined by the eps, 3.8% were esi 1, 16.7% were esi 2, 52.1% were esi 3, 17.9% were esi 4, and 9.5% were esi 5. the triage level was correct in 69.1% of cases. the rate of under-triage was 4.9%, and that of over-triage was 26.0%. 3.3. associated factors of over-triage and undertriage table 1 shows the results of univariate analysis. over-triage was significantly more common among patients aged 18–30 years (or = 2.19; 95% ci: 1.47–3.26; p < 0.001); patients with traumatic injuries (or = 2.11, 95% ci: 1.57–2.83, p < 0.001); patients who were hospitalized (or = 0.27, 95% ci: 0.18–0.41, p < 0.001); patients with abnormal respiratory rates (or = 0.64, 95% ci: 0.44–0.92, p = 0.016); patients with <90% oxygen saturation (or = 0.09, 95% ci: 0.01–0.66, p = 0.018); patients with severe pain (vas score of 8–10) (vas score of 0–7; or = 0.23, 95% ci: 0.08–0.65, p = 0.006); and patients with a glasgow coma scale score of <15 (or = 0.30, 95% ci: 0.13–0.66, p = 0.003). however, no factor was significantly associated with undertriage. based on multivariate analysis and when the influence of confounders was controlled, factors significantly associated with over-triage included age, chief complaint (injury or illness), arrival time, hospital admission, and pain severity. patients aged 18–30 years were over-triaged more often than patients aged ≥65 years (adjusted or = 1.73; 95% ci: 1.07–2.81; p = 0.026). patients with traumatic injuries were over-triaged more often than those without such injuries (adjusted or = 1.80, 95% ci: 1.29–2.52, p = 0.001). patients who visited the hospital during the evening shift (4:00–11:59 pm) were overtriaged more often than those who visited during the morning shift (8.00 am to 3.59 pm; adjusted or = 1.42, 95% ci: 1.01–2.00, p = 0.046). patients who were eventually hospitalized were over-triaged more often than those who were not hospitalized (adjusted or = 0.35, 95% ci: 0.22–0.54, p < 0.001), and patients with severe pain (vas scores of 8–10) were over-triaged more often than those with mild or moderate pain (vas scores of 0–7; adjusted or = 0.28, 95% ci: 0.10–0.84, p = 0.023). with regard to under-triage, age was a significant factor, when influence of confounders was controlled in analysis. patients aged 18–30 years were under-triaged more often than those aged ≥65 years (adjusted or = 3.05, 95% ci: 1.16–8.00, p = 0.023; table 3). 4. discussion this study revealed that in the ed of a university hospital in bangkok, thailand, the rate of under-triage was 4.9% and that of over-triage was 26.0%, using version 4 of the esi. these findings are consistent with those of a study of eds in england, in which the rate of under-triage was 3.3% and that of over-triage was 28.9% (9), and comparable with those of a study in an ed in a tertiary hospital in bangkok, in which the rate of correct triage was 68.7%, that of under-triage was 10.5%, and that of over-triage was 20.8% (19). however, these findings are not consistent with those of a previous large study of eds in 15 hospitals operated by the ministry of health and prevention of the united arab emirates, in which the rate of under-triage was 20.5% and that of over-triage was 79.5% (20). in 2014, the american college of surgeons committee on trauma defined proper criteria for evaluating the severity of injury from accidents, which are considered international standards. in one study in which these standards were used, rates of under-triage and over-triage were determined to be 5% at most and 25%–35%, respectively (21). these recommended standards were followed in the ed in which this study was conducted. the triage process is the first step in rendering health care. quality assurance of triage in the ed in our study starts with the selection of triage nurses who have worked in the ed for >5 years. they need to pass training in triage according to version 4 of the esi and to review knowledge about triage at least once a year. according to one study, the number of years of work as triage nurses in the ed was related to inaccuracy in determining the level of triage: nurses with <5 years of such experience were more likely to make errors in determining triage level (11). the number of hours spent in triage training was also significantly related to under-triage and over-triage (22). in the ed in this study, monthly triage quality assurance and case study review meetings could decrease rates of mistriage, which would be consistent with the findings of a literature review, in which nurses in patient triage needed nursing review activities to maintain triage accuracy (23). this study showed that five factors were associated with overtriage. first, patients aged 18–30 years were over-triaged more often than those aged ≥65 years. this finding was comparable with that in a previous study, in which over-triage usually occurred in patients aged ≥ 18 years (9), and was consistent with another study in this regard (10), in which patients aged 18–30 years were more likely than patients aged ≥65 years to be over-triaged for high-acuity conditions (esi levels 1 and 2) and for moderate-acuity conditions (esi level 3). this finding could be explained by the fact that the younger patients were at higher risk for injuries in traffic accidents and occupational accidents. teenagers in this age group had complicated chief complaints similar to those in adults; moreover, injuries to their organs caused more radical physical and physiological changes, such as abdominal pain and dyspnea (24). for these reasons, triage nurses may have selected over-triage. second, patients with traumatic injuries were over-triaged this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e57 more often than those without such injuries. this finding was consistent with that of a previous study, in which the rate of over-triage for patients with traumatic injuries involving the chest or abdomen was as high as 87.50% (25). a possible explanation was that patients with traumatic injuries usually presented with complicated symptoms and required many laboratory tests. in addition, the eps needed to consult specialists in other departments, such as surgeons, orthopedic surgeons, and plastic surgeons. third, patients visiting the ed during the evening shift (4:00–11:59 pm) were over-triaged more often than patients visiting during the morning shift (8.00 am–3.59 pm). this finding was comparable with that of a previous study (10). a possible explanation was that many hospital departments were closed during the evening shift, and the ed, which was therefore responsible for both emergency and non-emergency patients during the evening shift, became crowded. for non-emergency patients, laboratory tests and specialty consultation were required, but such resources were insufficient during the evening shift (26). fourth, hospitalized patients were over-triaged more often than non-hospitalized patients. this finding was consistent with that of a previous study of eds in the united states, in which hospitalized patients were over-triaged 85% more often than non-hospitalized patients (9), and with that of a study in which hospitalized patients classified as having esi levels 1 and 2 conditions were over-triaged more often than their non-hospitalized counterparts (25). hospitalization was also identified as the reason why length of stay in the emergency department was ≥4 h (27). a possible explanation of this finding was that for most hospitalized patients, triage nurses usually assessed chief complaints, vital signs, and laboratory test results and consulted with specialists (27). most admitted patients had comorbidities. triage nurses might decide to over-triage such patients because they require dedicated management, special tests, pathological examinations, and radiological tests (28). because triage nurses might anticipate whether patients’ symptoms, comorbidities, and results of special tests indicate the need for hospital admission, they might be more likely to overtriage. fifth, patients with severe pain (vas scores of 8–10) were over-triaged more often than patients with mild or moderate pain (vas scores of 0–7). this finding was consistent with that of a previous study in which patients with severe pain were 79% more likely than those with less pain to be overtriaged (9, 10). vas score might be considered abstract, and patients’ pain scores might not represent the actual pain that they feel; for this reason, triage nurses may perform overtriage. the use of only a numerical scale of 1–10 to rate pain might result in more mistriage than would the additional use of pictures to rate pain (9). with regard to under-triage, patients aged 18–30 years were under-triaged more often than patients aged ≥65 years. this finding was similar to that of a previous study (29) in which patients aged 18–30 years were under-triaged 78% more often than patients aged ≥65 years for high-acuity conditions (esi level 1 or 2) and were more likely to be under-triaged for moderate-acuity conditions (esi level 3). in that study, 34% of patients received under-triage. in another study, patients younger than 30 years were at higher risk for under-triage than were patients of other ages (30). in this study, patients aged 18–30 years were at higher risk for both over-triage and under-triage; therefore, triage nurses must be more careful in determining triage level for patients in this age range. the results of this study imply that nurses should perform triage according to triage guidelines based on the esi and should review triage criteria regularly. they should also be aware of factors associated with mistriage: age, chief complaint, arrival time, hospital admission, and pain severity. 5. limitation this study had many limitations. first, it was a single-center study in which data were collected from the ed of a university hospital in bangkok, thailand; therefore, the results might not apply to other areas, and the external validity of data may be poor. second, the study was a retrospective review of medical records; although neutrality was maintained in every way possible, selection bias might have existed. third, data were unavailable for multiple variables, including respiratory rate, oxygen saturation, body temperature, pain severity (vas score) and capillary blood glucose concentration. last, unmeasured confounding factors may have been present. the only measure used to triage was the esi, and esi levels 1–5 were not analyzed separately. in future studies, rates of and factors affecting under-triage and over-triage should be analyzed separately for the different esi levels. 6. conclusion over-triage occurs at a substantially higher rate than does under-triage. five factors associated with over-triage were age, chief complaint (trauma or non-trauma), arrival time, hospital admission, and pain score, whereas age was the only factor related to under-triage. 7. declarations 7.1. acknowledgments the authors are grateful to the navamindradhiraj university research fund for pub. we would like to thank all participating staff at ed, faculty of medicine vajira hospital, navamindradhiraj university, for facilitating data collection and access in the present study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 6 7.2. conflict of interest the authors have no conflicting interests to declare. 7.3. funding and support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution conceptualization: thongpitak huabbangyang, siriwimol buathong and rapeeporn rojsaengroeng; methodology: thongpitak huabbangyang, siriwimol buathong, agasak silakoon, gawin tiyawat, alissara vanichkulbodee, jiraporn srion and rapeeporn rojsaengroeng; software: thongpitak huabbangyang; validation: thongpitak huabbangyang and rapeeporn rojsaengroeng; formal analysis: thongpitak huabbangyang; investigation: thongpitak huabbangyang, siriwimol buathong and rapeeporn rojsaengroeng; resources: thongpitak huabbangyang, siriwimol buathong and rapeeporn rojsaengroeng; data curation: thongpitak huabbangyang; writing – original draft: thongpitak huabbangyang; writing review & editing: thongpitak huabbangyang and rapeeporn rojsaengroeng; visualization: thongpitak huabbangyang and rapeeporn rojsaengroeng; supervision: thongpitak huabbangyang; project administration: thongpitak huabbangyang; funding acquisition: thongpitak huabbangyang. all authors read and approved the final version of manuscript. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. 7.6. using artificial intelligence chatbots none. references 1. raita y, goto t, faridi mk, brown df, camargo ca, hasegawa k. emergency department triage prediction of clinical outcomes using machine learning models. crit care. 2019;23(1):64. 2. farrohknia n, castrén m, ehrenberg a, lind l, oredsson s, jonsson h, et al. emergency department triage scales and their components: a systematic review of the scientific evidence. scand j trauma resusc emerg med. 2011;19:42. 3. fernandes m, vieira sm, leite f, palos c, finkelstein s, sousa jm. clinical decision support systems for triage in the emergency department using intelligent systems: a review. artif intell med. 2020;102:101762. 4. af ugglas b, lindmarker p, ekelund u, djärv t, holzmann mj. emergency department crowding and mortality in 14 swedish emergency departments, a cohort study leveraging the swedish emergency registry (svar). plos one. 2021;16(3):e0247881. 5. mistry b, de ramirez ss, kelen g, schmitz ps, balhara ks, levin s, et al. accuracy and reliability of emergency department triage using the emergency severity index: an international multicenter assessment. ann emerg med. 2018;71(5):581-7. e3. 6. gilboy n, tanabe p, travers da, rosenau am, eitel dr. emergency severity index, version 4: implementation handbook. rockville, md: agency for healthcare research and quality; 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[accuracy of emergency triage system in emergency room at chiangrai prachanukroh hospital: emergency severity index (esi) compared to canadian triage and acuity cale (ctas)]. crmj. 2021;13(3):147-59. thai. 26. ye l, zhou g, he x, shen w, gan j, zhang m. prolonged length of stay in the emergency department in highacuity patients at a c hinese tertiary hospital. emerg med australas. 2012;24(6):634-40. 27. sankham p, utriyaprasit k, tankumpuan t, khruekarnchana p. [predictors of older patients’ stay in the emergency department]. jtnmc. 2022;37(1):125-45. thai. 28. sweeny a, keijzers g, o’dwyer j, arendts g, crilly j. predictors of a long length of stay in the emergency department for older people. intern med j. 2020;50(5):572-81. 29. rashid k, ullah m, ahmed st, sajid mz, hayat ma, nawaz b, et al. accuracy of emergency room triage using emergency severity index (esi): independent predictor of under and over triage. cureus. 2021;13(12):e20229. 30. benjamin er, khor d, cho j, biswas s, inaba k, demetriades d. the age of undertriage: current trauma triage criteria underestimate the role of age and comorbidities in early mortality. j emerg med. 2018;55(2):278-87. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 8 table 1: patient demographics and clinical characteristics variables overall (n = 1000) triage result correct (n = 691) over-triage (n = 260) under-triage (n = 49) gender n % n % n % n % male 524 (52.4) 356 (51.5) 146 (56.2) 22 (44.9) female 476 (47.6) 335 (48.5) 114 (43.8) 27 (55.1) age (years) 47.94 ± 21.81 49.59 ± 21.92 44.15 ± 20.82 44.67 ± 23.00 18–30 years 295 (29.5) 180 (26.0) 95 (36.5) 20 (40.8) 30–49 years 223 (22.3) 159 (23.0) 55 (21.2) 9 (18.4) 50–65 years 219 (21.9) 149 (21.6) 61 (23.5) 9 (18.4) ≥65 years 263 (26.3) 203 (29.4) 49 (18.8) 11 (22.4) comorbidities no 573 (57.3) 386 (55.9) 162 (62.3) 25 (51.0) yes 427 (42.7) 305 (44.1) 98 (37.7) 24 (49.0) type of patients non-trauma 666 (66.6) 489 (70.8) 139 (53.5) 38 (77.6) trauma 334 (33.4) 202 (29.2) 121 (46.5) 11 (22.4) transportation to ed walk in 915 (91.5) 625 (90.4) 243 (93.5) 47 (95.9) ambulance 85 (8.5) 66 (9.6) 17 (6.5) 2 (4.1) arrival time morning shift (8.00–15.59) 346 (34.6) 251 (36.3) 82 (31.5) 13 (26.5) evening shift (16.00–23.59) 452 (45.2) 297 (43.0) 126 (48.5) 29 (59.2) night shift (0.00–7.59) 202 (20.2) 143 (20.7) 52 (20.0) 7 (14.3) chief complaints abdominal pain 99 (9.9) 74 (10.7) 22 (8.5) 3 (6.1) allergic 17 (1.7) 12 (1.7) 5 (1.9) 0 (0.0) altered mental status 34 (3.4) 29 (4.2) 3 (1.2) 2 (4.1) animal bites 38 (3.8) 20 (2.9) 18 (6.9) 0 (0.0) chest pain 31 (3.1) 27 (3.9) 1 (0.4) 3 (6.1) dizziness 38 (3.8) 30 (4.3) 7 (2.7) 1 (2.0) dysrhythmia 6 (0.6) 5 (0.7) 1 (0.4) 0 (0.0) edema 3 (0.3) 3 (0.4) 0 (0.0) 0 (0.0) ear, nose, and throat 24 (2.4) 11 (1.6) 12 (4.6) 1 (2.0) fever 72 (7.2) 48 (6.9) 19 (7.3) 5 (10.2) genitourinary 20 (2.0) 19 (2.7) 0 (0.0) 1 (2.0) gastrointestinal bleeding 19 (1.9) 12 (1.7) 6 (2.3) 1 (2.0) headache 10 (1.0) 7 (1.0) 2 (0.8) 1 (2.0) hypertension 5 (0.5) 4 (0.6) 1 (0.4) 0 (0.0) labor pain 29 (2.9) 25 (3.6) 1 (0.4) 3 (6.1) lower respiratory tract infection 7 (0.7) 6 (0.9) 0 (0.0) 1 (2.0) musculoskeletal (atraumatic) 31 (3.1) 24 (3.5) 3 (1.2) 4 (8.2) musculoskeletal (isolated trauma) 29 (2.9) 19 (2.7) 7 (2.7) 3 (6.1) neurologic 29 (2.9) 19 (2.7) 9 (3.5) 1 (2.0) nausea, vomiting, and diarrhea 42 (4.2) 25 (3.6) 14 (5.4) 3 (6.1) seizure 13 (1.3) 10 (1.4) 2 (0.8) 1 (2.0) shortness of breath 68 (6.8) 50 (7.2) 14 (5.4) 4 (8.2) skin, nails, and hair 4 (0.4) 0 (0.0) 4 (1.5) 0 (0.0) substance abuse 4 (0.4) 2 (0.3) 2 (0.8) 0 (0.0) syncope 21 (2.1) 15 (2.2) 6 (2.3) 0 (0.0) trauma 254 (25.4) 155 (22.4) 91 (35.0) 8 (16.3) upper respiratory tract infection 29 (2.9) 20 (2.9) 7 (2.7) 2 (4.1) weakness 7 (0.7) 5 (0.7) 1 (0.4) 1 (2.0) wound 1 (0.1) 1 (0.1) 0 (0.0) 0 (0.0) other 16 (1.6) 14 (2.0) 2 (0.8) 0 (0.0) hospital admission no 713 (71.3) 452 (65.4) 227 (87.3) 34 (69.4) yes 287 (28.7) 239 (34.6) 33 (12.7) 15 (30.6) critical outcomes discharge 668 (66.8) 415 (60.1) 220 (84.6) 33 (67.3) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e57 table 1: patient demographics and clinical characteristics variables overall (n = 1000) triage result correct (n = 691) over-triage (n = 260) under-triage (n = 49) hospital admission 287 (28.7) 239 (34.6) 33 (12.7) 15 (30.6) hospital transfer 39 (3.9) 31 (4.5) 7 (2.7) 1 (2.0) death 4 (0.4) 4 (0.6) 0 (0.0) 0 (0.0) against advice 2 (0.2) 2 (0.3) 0 (0.0) 0 (0.0) systolic blood pressure (mmhg) mean ± sd 137.98±26.74 138.38 ± 27.37 137.86 ± 25.32 132.92 ± 25.14 <90 mmhg 10 (1.0) 10 (1.4) 0 (0.0) 0 (0.0) 90-160 mmhg 817 (81.7) 559 (80.9) 214 (82.3) 44 (89.8) >160 mmhg 173 (17.3) 122 (17.7) 46 (17.7) 5 (10.2) diastolic blood pressure (mmhg) mean ± sd 82.23 ± 16.73 82.12 ± 17.32 83.15 ± 15.26 78.94 ± 15.66 <60 61 (6.1) 44 (6.4) 13 (5.0) 4 (8.2) 60-110 888 (88.8) 610 (88.3) 234 (90.0) 44 (89.8) >110 51 (5.1) 37 (5.4) 13 (5.0) 1 (2.0) heart rate (beats/min) 88.15 ± 19.4 88.23 ± 19.85 87.97 ± 18.67 87.98 ± 16.97 <60 34 (3.4) 25 (3.6) 9 (3.5) 0 (0.0) 60-100 765 (76.5) 523 (75.7) 201 (77.3) 41 (83.7) >100 201 (20.1) 143 (20.7) 50 (19.2) 8 (16.3) respiratory rate (cycles/min) 20.24 ± 4.08 20.51 ± 4.44 19.59 ± 3.02 19.98 ± 3.28 <12 2 (0.2) 2 (0.3) 0 (0.0) 0 (0.0) 12-20 768 (76.8) 512 (74.1) 215 (82.7) 41 (83.7) >20 214 (21.4) 163 (23.6) 44 (16.9) 7 (14.3) unmeasurable 16 (1.6) 14 (2.0) 1 (0.4) 1 (2.0) oxygen saturation (%) median (iqr) 98(97 100) 98(96 100) 99(97.5 100) 98(96 99) <90 31 (3.1) 30 (4.3) 1 (0.4) 0 (0.0) >90 687 (68.7) 478 (69.2) 179 (68.8) 30 (61.2) unmeasurable 282 (28.2) 183 (26.5) 80 (30.8) 19 (38.8) body temperature (°c) 37.16 ± 1.08 37.15 ± 1.07 37.23 ± 1.11 36.94 ± 1.02 <37.5 462 (46.2) 331 (47.9) 105 (40.4) 26 (53.1) ≥37.5 176 (17.6) 130 (18.8) 39 (15.0) 7 (14.3) unmeasurable 362 (36.2) 230 (33.3) 116 (44.6) 16 (32.7) pain score mean ± sd 6.90 ± 2.45 7.12 ± 2.48 5.88 ± 2.26 7.67 ± 1.86 mild (0–3) 13 (1.3) 10 (1.4) 3 (1.2) 0 (0.0) moderate (4–7) 54 (5.4) 35 (5.1) 17 (6.5) 2 (4.1) severe (8–10) 59 (5.9) 50 (7.2) 5 (1.9) 4 (8.2) none (missing) 874 (87.4) 596 (86.3) 235 (90.4) 43 (87.8) glasgow coma scale median (iqr) 15(15 15) 15(15 15) 15(15 15) 15(15 15) <15 70 (7.0) 59 (8.5) 7 (2.7) 4 (8.2) 15 930 (93.0) 632 (91.5) 253 (97.3) 45 (91.8) capillary blood glucose (%) mean ± sd 168.67±89.13 167.87 ± 89.39 170.3 ± 90.27 175.9 ± 89.87 <100 29 (2.9) 21 (3.0) 7 (2.7) 1 (2.0) ≥100 173 (17.3) 138 (20.0) 26 (10.0) 9 (18.4) none (missing) 798 (79.8) 532 (77.0) 227 (87.3) 39 (79.6) data are presented as number (%), mean ± standard deviation or median (interquartile range). sd: standard deviation; iqr: interquartile range; ed: emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 10 table 2: univariable analysis for factors associated with under-triage and over-triage variables over-triage under-triage or 95%ci p-value or 95%ci p-value gender male 1.00 reference 1.00 reference female 0.83 (0.62 1.11) 0.202 1.30 (0.73 2.33) 0.371 age (years) 18–30 years 2.19 (1.47 3.26) <0.001* 2.05 (0.96 4.4) 0.065 30–49 years 1.43 (0.93 2.22) 0.107 1.04 (0.42 2.58) 0.925 50–65 years 1.70 (1.10 2.61) 0.016* 1.11 (0.45 2.76) 0.814 ≥65 years 1.00 reference 1.00 reference comorbidities no 1.00 reference 1.00 reference yes 0.77 (0.57 1.03) 0.073 1.21 (0.68 2.17) 0.510 type of patients non-trauma 1.00 reference 1.00 reference trauma 2.11 (1.57 2.83) <0.001* 0.70 (0.35 1.40) 0.313 transportation to ed walk in 1.00 reference 1.00 reference ambulance 0.66 (0.38 1.15) 0.145 0.40 (0.10 1.70) 0.215 arrival time morning shift (8.00–15.59) 1.00 reference 1.00 reference evening shift (16.00–23.59) 1.30 (0.94 1.80) 0.115 1.89 (0.96 3.7) 0.066 night shift (0.00–7.59) 1.11 (0.74 1.67) 0.603 0.95 (0.37 2.42) 0.906 hospital admission no 1.00 reference 1.00 reference yes 0.27 (0.18 0.41) <0.001* 0.83 (0.45 1.56) 0.572 systolic blood pressure (mmhg) normal 1.00 reference 1.00 reference abnormal 0.91 (0.63 1.32) 0.619 0.48 (0.19 1.24) 0.129 diastolic blood pressure (mmhg) normal 1.00 reference 1.00 reference abnormal 0.84 (0.52 1.33) 0.454 0.86 (0.33 2.22) 0.749 heart rate (beats/min) normal 1.00 reference 1.00 reference abnormal 0.91 (0.65 1.28) 0.601 0.61 (0.28 1.32) 0.209 respiratory rate (cycles/min) normal 1.00 reference 1.00 reference abnormal 0.64 (0.44 0.92) 0.016* 0.53 (0.23 1.20) 0.129 oxygen saturation (%) <90 0.09 (0.01 0.66) 0.018* na >90 1.00 reference 1.00 reference body temperature (°c) <37.5 1.00 reference 1.00 reference ≥37.5 0.95 (0.62 1.44) 0.794 0.69 (0.29 1.62) 0.389 pain score mild/moderate (0–7) 1.00 reference 1.00 reference severe (8–10) 0.23 (0.08 0.65) 0.006* 1.80 (0.31 10.30) 0.509 glasgow coma scale <15 0.30 (0.13 0.66) 0.003* 0.95 (0.33 2.74) 0.928 15 1.00 reference 1.00 reference capillary blood glucose (%) <100 1.00 reference 1.00 reference ≥100 0.57 (0.22 1.47) 0.240 1.37 (0.16 11.37) 0.771 or: odds ratio; ci: confident interval; ed: emergency department; na: data not applicable. *: significant difference; crude odds ratio estimated by multinomial logistic regression. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e57 table 3: multivariable analysis for factors associated with under-triage and over-triage variables over-triage under-triage ora d j 95%ci p-value ora d j 95%ci p-value age (years) 18–30 1.73 (1.07 2.81) 0.026* 3.05 (1.16 8.00) 0.023* 30–49 1.24 (0.76 2.01) 0.391 1.40 (0.52 3.81) 0.506 50–65 1.49 (0.93 2.38) 0.094 1.23 (0.47 3.22) 0.675 ≥65 1.00 reference 1.00 reference type of patients non-trauma 1.00 reference 1.00 reference trauma 1.80 (1.29 2.52) 0.001* 0.73 (0.34 1.57) 0.424 arrival time morning shift (8.00–15.59) 1.00 reference 1.00 reference evening shift (16.00–23.59) 1.42 (1.01 2.00) 0.046* 1.68 (0.84 3.36) 0.142 night shift (0.00–7.59) 1.21 (0.79 1.86) 0.383 0.83 (0.32 2.17) 0.705 hospital admission no 1.00 reference 1.00 reference yes 0.35 (0.22 0.54) <0.001* 0.95 (0.46 1.95) 0.890 pain score mild/moderate (0–7) 1.00 reference 1.00 reference severe (8–10) 0.28 (0.10 0.84) 0.023* 1.81 (0.30 10.8) 0.514 oradj: adjusted odds ratio; ci: confident interval; na: data not applicable. variables were included in multivariable model due to having p-value < 0.200 in uni-variable analysis. *: significant difference; adjusted odds ratio estimated by multinomial logistic regression. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references emergency. 2017; 5 (1); e60 rev i ew art i c l e pregnancy screening before diagnostic radiography in emergency department; an educational review abdelrahman ibrahim abushouk1, morteza sanei taheri2, parichehr pooransari3, sahar mirbaha4, alaleh rouhipour5, alireza baratloo6 ∗ 1. faculty of medicine, ain shams university, cairo, egypt. 2. department of radiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of ob&gyn, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. 5. pediatric specialist, private researcher, tehran, iran. 6. department of emergency medicine, tehran university of medical sciences, tehran, iran. received: december 2016; accepted: february 2017; published online: 28 february 2017 abstract: in modern medical practice, there is an increasing dependence on imaging techniques in most medical specialties. radiation exposure during pregnancy may have serious teratogenic effects to the fetus. therefore, checking the pregnancy status before imaging women of child bearing age can protect against these effects. lack of international regulations and standard protocols exposes the patient to unexpected fetal radiation effects and the health professionals to medicolegal suits. recently, the american academy of radiology and the european community of medical ionizing radiation protection released national guidelines regarding pregnancy screening before imaging potentially pregnant females. however, different methods of pregnancy screening exist among different radiology centers. this review aims to discuss the most recent guidelines for imaging females of childbearing age and highlight the need for an international regulation to guide pregnancy screening before diagnostic radiation exposure. keywords: radiation; imaging; pregnancy; screening; emergency department. © copyright (2017) shahid beheshti university of medical sciences cite this article as: abushouk a, sanei taheri m, pooransari p, mirbaha s, rouhipour a, baratloo a. pregnancy screening before diagnostic radiography in emergency department; an educational review. 2017; 5(1): e60. 1. introduction i n modern medical practice, there is an increasing dependence on imaging techniques in most medical specialties, especially emergency medicine (1). radiation exposure during pregnancy may have serious teratogenic effects to the fetus. in 2000, the international commission on radiation protection published a statement, which indicated that thousands of pregnant women are unintentionally exposed to ionizing radiation annually (2). it was reported that 1% of reproductive age females who had an abdominal imaging procedure were pregnant in their first trimester (3-5). ∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. tel: +989122884364; email: alirezabaratloo@yahoo.com therefore, checking the pregnancy status before imaging women of child bearing age can protect against radiation teratogenic effects. lack of international regulations and standard protocols exposes the patients to unexpected radiation effects and the health professionals to medicolegal suits. however, there are different approaches in this regard. some centers offer a costless urine pregnancy test. others obtain an informed written consent or a signed questionnaire indicating women’s awareness of any imaging risks and acknowledging the lack of a pregnancy probability before radiation exposure (6). due to lack of resources, some centers acts according to the patient’s trust (7). despite the absence of a standard regulation to guide radiological testing in these situations, several organizations such as the national academy of sciences, national institute of environmental health, and the international committee on radiological protection recthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. abushouk et al. 2 ommended radiologists to ask women about their pregnancy status and menstrual date before radiological testing (2). in 2007, applegate initially clarified the need for such guideline and stated what aspects it should include. according to his statement, this guideline should address the method of screening, documentation of the results, protection of patient’s privacy, and situation management in case of emergency radiological testing (7). the evidence regarding the physicians’ awareness of possible radiation risks to the fetus is controversial. in surveys by ratnaplan et al., and bentur et al., physicians had a strong perception of high radiation associated teratogenic risk; therefore, they limited requesting ionizing radiation procedures for pregnant women (8). in another survey by ikpeme et al., 98.8% of physicians supplied radiological practitioners with lacking information regarding the pregnancy status of reproductive age women, which could be attributed to lack of awareness or underestimation of radiation-induced fetal risks (9). this review discusses the current literature trend towards pregnancy screening before radiological imaging of reproductive age women and highlights the need to establish an international regulation to guide these diagnostic procedures. a) patients and physicians awareness: risks of radiation to the fetus as illustrated in table 1, exposure within the first two weeks of conception is only associated with a risk of pregnancy loss at high radiation doses above 0.1 gy (10 rad). later exposure until the 15th week is associated with developmental anomalies, only at doses exceeding 0.1 gy (10). exposure after the first 15 weeks of pregnancy only poses risk of central nervous system deficits at extremely high doses of more than 0.2 gy (20 rad) (2, 11). the overall lifetime radiation-induced cancer for an exposed fetus to 0.05 gy (5 rad) in the period following the 15th week of pregnancy is estimated to be 2% (12, 13). a detailed correlation between the fetal radiation dose and the risk of childhood cancer is illustrated in table 2. -medicolegal issues defining the pregnancy status and supplying radiological practitioners with all relevant information before radiological imaging is the prime responsibility of the physician recommending the procedure. on the other hand, the role of the medical physicist is calculating the absorbed dose of radiation in a diagnostic procedure that may potentially reach an unexpected conceptus. it is the duty of the radiologist to estimate the risk of these doses and find means to minimize the associated risk (14). few policies exist to determine the legal liability of both clinicians and radiologists in case of harmful radiation exposure, leaving medical professionals vulnerable to malpractice suits and patients liable to risks of radiation exposure (7). this was adequately stated by berlin in 1996 that highlighted the absence of a governmental regulation or a national guideline, which obligates radiologists to investigate the pregnancy status of women in childbearing age before radiation exposure (15). later, in 2000, the international committee on radiological protection published a recommendation that encourages physicians to inform radiologists regarding the pregnancy status of referred patients and advises radiologists to adequately verify the pregnancy status of women before radiation exposure (2). safety measures different radiation procedures have different precautions, depending on the type of radiation and the body area to be imaged (7). there is a defined threshold radiation dose of 0.1gy (10 rad), below which there is no practical risk of radiation-induced abortion or congenital malformations. the usual radiation dose, delivered during plain x-ray imaging, is usually less than 0.02 gy (2 rad), while it rises to 0.02-0.035 gy (2-3.5 rad) during computed tomography (ct). based on these calculations, even repeated abdominal or pelvic ct imaging should pose no theoretical risk to the fetus (16). however, the national council on radiation protection and measurements stated a principle entitled "as low as reasonably achievable" or "alara" which highlighted that no radiation exposure level is entirely free of risk and that the safety of the procedure should be evaluated in terms of benefit versus risk (17). in 2006, the national academy of sciences issued a report which highlighted the link between low levels of radiation exposure and the risk of teratogenesis and cancer induction (18). imaging other body areas as the chest or extremities holds lower risk to the fetus as long as the woman is positioned properly and the diagnostic procedure is medically justified (19, 20). to further minimize fetal exposure, the 10-day and 28-day rules were introduced. they state that radiological procedures that deliver low doses to the fetus should be restricted to the first 28 days of last menstrual cycle, while those that deliver high fetal doses (> 0.01gy to the fetus) as pelvic computed tomography (ct) and contrast radiological procedures should be restricted to the first 10 days of the menstrual cycle. these rules apply to patients with a regular cycle length of 28 days and should be modified according to cycle length (21, 22). despite the potential benefits of applying this rule, it creates some difficulty scheduling diagnostic tests; therefore, it is no longer applied in most radiology centers (7). b) what to do? despite the absence of a standard regulation to guide imaging testing in these situations, several respected authorities released non-regulatory national guidelines for imaging potentially pregnant women. these recommendations are primarily based on expert committee reports or the clinical experience of respected authorities (grade d recommendation; appendix b). further studies with stronger evidence are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1); e60 table 1: risk of teratogenic malformations according to dose of radiation and gestational age on exposure gestational age (week) radiation dose < 5 rad 5 10 rad > 10 rad prior to conception none none none 1s t -2n d none none possible spontaneous abortion 3r d 8t h none subclinical effects possible malformation 9t h 15t h none subclinical effects increased risk of iq deficits 16t h 25t h none none iq deficits not detectable at diagnostic doses >25t h none none none applicable to diagnostic medicine table 2: fetal radiation dose correlation with risk of childhood cancer as stated by the health protection agency centre for radiation chemical and environmental hazards estimated fetal dose (rad) radiological examination risk of childhood cancer 0.0001-0.001 x-ray (head and thoracic spine) ct scan (head and neck). breast mammography < 1 in 1,000,000 0.001-0.01 ct pulmonary angiogram lung ventilation scans 1 in 1,000,000 to 1 in 100,000 0.01-0.1 x-ray (abdomen, pelvis, hip, and barium meal) ct scan (chest and liver) 1 in 100,000 to 1 in 10,000 0.1-1 x-ray (lumbar spine and barium enema) ct scan (abdomen and lumbar spine) myocardial scan, bone scan, and tumor scan 1 in 10,000 to in 1,000 1-5 ct scan (pelvis and abdomen) whole body scan 1 in 1,000 to 1 in 200 figure 1: american college of radiology (acr) practice guidelines for imaging pregnant and potentially pregnant women. needed to establish a higher grade guideline for imaging potentially pregnant females. some of the available recommendations in this regard are as follow: recommendations of american college of radiology (acr) in 2008, the acr released a national guideline for imaging potentially pregnant women (figure 1). however, acr strongly recommended that each institution should develop its own policy because every individual case may require modification of the highest grade guidelines (16). aar recommendation composes different steps: history taking obtaining history from the patient’s record or direct questioning may be feasible and reliable for the inpatients. further assessment of the reproductive status of these females can further minimize the risk of unintended fetal exposure to radiation (16). defining the type of the imaging procedure is essential to determine the risk it poses to a potential conceptus. some imaging procedures result in a low level of uterine exposure that the decision to proceed with the imaging test is not influenced by the pregnancy status. these procedures include radiographic imaging of the head, the chest (with the possible exception of the third trimester), and extremities (18, 22). performing mammography is not contraindicated during pregnancy (23). in these cases, determining pregnancy status as a routine part of medical history is recommended through direct questioning of the patient (16). obtaining information from patients in the reproductive age can be performed through direct verbal questioning or written formats. the advantages of written formats include standardizing the questions and further benefits of documentation (7). questions should extend beyond pregnancy status to assess the menstrual and reproductive history of the female because this may enhance the probability of detecting an unexpected pregnancy (16). the last menstrual period should have been completed within 4 weeks from the radiological examination because radiation exposure within this period holds no significant risk to the embryo (24). the use of contraceptive methods should not rule out pregnancy. while contraceptive use decreases the probability of pregnancy, the efficacy of the used method is a matter of professional judgment. therefore, if doubt exists, these guidelines should be followed (14, 16). pregnancy testing some radiological tests are associated with a high level of radiation exposure to the uterus as direct imaging of the pelvis, abdominal/pelvic computed tomography, hysterosthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. abushouk et al. 4 alpingography, and diagnostic/ interventional pelvic angiography (25). in these cases, documenting the pregnancy status, preferably through urine pregnancy test (within 72 hours before the imaging), is strongly recommended (26, 27). the results of a urine pregnancy test should be interpreted carefully. a positive result may require delaying, modification or cancelling of the procedure as long as no emergency state is present. on the other hand, a negative result should not substitute verbal or written questioning of the patient about her menstrual history and possibility of pregnancy (16). in case of high-risk procedures, external monitoring of radiation dose, using monitors placed around the patient’s pelvis, should be considered. documentation of the results may be helpful in planning future imaging procedures (14). while positive pregnancy tests are useful in directing further justification, negative pregnancy tests (performed before the period is due) should be interpreted carefully. in particular, a negative urinary pregnancy test, taken at the point of care, should be confirmed with a more sensitive laboratory test (16, 28). final decision if pregnancy could be excluded through the earlier steps, a medically indicated radiological procedure can be performed. if pregnancy is established, the patient should be informed and the clinician should be consulted about delaying, modifying or cancelling the test upon reviewing the justification for radiological procedure and assessment of the possible risk versus the desired benefit (16). however, if uncertainty prevails, the medical physicist should consult the radiologist and the clinician to determine the best management plan according to the protocol of the host institution. if the situation is urgent, the clinician should wave pregnancy screening and the physicist should document the emergency condition that indicated waiving the test in the patient record (14). recommendations of european community of ionizing radiation exposure the european community of medical ionizing radiation protection released its guidelines for protecting women of childbearing age in 2002, with a special amendment in 2007. the main headings of this recommendation are: in case of a female in childbearing age, the clinician and radiologist should ask the patient directly if she is pregnant. if pregnancy cannot be excluded, the female should be treated as pregnant. if there is an emergency indication for imaging, justification of radiation exposure should be documented and optimization of exposure of the mother and her fetus should be considered (24, 29, 30). c) special situations: pregnancy screening in adolescent girls in case of pregnancy testing in unmarried girls under the age of 18 years, whose healthcare is the responsibility of the parent or the guardian (7), the radiologist must obtain the parent/guardian’s consent to assess the pregnancy status of his/her minor (31). in case of approval, the radiologist can directly ask the girl about her menstrual history or pregnancy status (32). the difficulties associated with questioning minors about their pregnancy status should be addressed by a local protocol that considers associated legal issues (14, 16). -radiological testing in emergency situations if the medical condition is urgent, the clinician should wave the screening and the justification for this waiver should be documented (33). radiological examination of anaesthetized patients should be determined by a local institutional policy where pregnancy condition is established before anesthesia (16). other cases that may require waiving pregnancy screening may include sexually inactive females and females with infertility (14). d) managing missed cases: if a patient went through a radiological test while being pregnant, the clinician should counsel the patient regarding the event and perform a prospective risk assessment (16). as the possible effects depend on the absorbed dose and conception age, these data need to be known to offer an accurate risk assessment. although most radiological examinations pose a small risk to the fetus, the patient should be informed in a non-alarming way about the possible risks of radiation (14). in case of exposure to a dose exceeding 0.1gy (10 rad) in the first 15 weeks of pregnancy, counseling regarding the risks of radiation exposure during pregnancy is a must (11). otherwise, the woman should be advised to seek standard obstetric care. e) administration of contrast media: low molecular weight contrast media cross the human placenta and appear in the fetal circulation few minutes after maternal injection with clinical doses. interestingly, the acr does not recommend routine pregnancy screening before the use of iodinated contrast media, which are classified by the fda as category b medications (34). although no case of teratogenesis have been recorded with gadolinium based substances, the acr recommends using gadolinium contrast media with caution at the lowest diagnostic doses, and only when critically justified (34, 35). 2. conclusion: pregnancy screening before radiation exposure in reproductive age females is essential. establishing an international regulation or standard protocols is essential to guide clinicians and radiologists through the appropriate interventions to detect pregnancy in these situations. in the light of the current evidence, urine pregnancy testing should not be perthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1); e60 formed in every female, applying for radiological examination. 3. appendix 3.1. acknowledgements we express our acknowledgment to the emergency medicine faculty members of shahid beheshti university of medical sciences. 3.2. authors contributions all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data collection and interpretation. 3.3. funding support none. 3.4. conflict of interest none. references 1. linton ow, mettler jr fa. national conference on dose reduction in ct, with an emphasis on pediatric patients. american journal of roentgenology. 2003;181(2):321-9. 2. pregnancy i. medical radiation icrp publication 84. ann icrp. 2000;30(1). 3. mccollough ch, schueler ba, atwell td, braun nn, regner dm, brown dl, et al. radiation exposure and pregnancy: when should we be concerned? 1. radiographics. 2007;27(4):909-17. 4. hennrikus wl, shaw ba, gerardi ja. prevalence of positive preoperative pregnancy testing in teenagers scheduled for orthopedic surgery. journal of pediatric orthopaedics. 2001;21(5):677-9. 5. wheeler m, cote cj. preoperative pregnancy testing in a tertiary care children’s hospital: a medico-legal conundrum. survey of anesthesiology. 2000;44(2):123-4. 6. el-khoury gy, madsen mt, blake me, yankowitz j. a new pregnancy policy for a new era. american journal of roentgenology. 2003;181(2):335-40. 7. applegate k. pregnancy screening of adolescents and women before radiologic testing: does radiology need a national guideline? journal of the american college of radiology. 2007;4(8):533-6. 8. ratnapalan s, bona n, chandra k, koren g. physicians’ perceptions of teratogenic risk associated with radiography and ct during early pregnancy. american journal of roentgenology. 2004;182(5):1107-9. 9. akintomide a, ikpeme a. radiation safety of women of the reproductive age: evaluation of the role of referring physicians. journal of family medicine and primary care. 2014;3(3):243-6. 10. wang pi, chong st, kielar az, kelly am, knoepp ud, mazza mb, et al. imaging of pregnant and lactating patients: part 1, evidence-based review and recommendations. american journal of roentgenology. 2012;198(4):778-84. 11. valentin j. biological effects after prenatal irradiation (embryo and fetus): icrp publication 90 approved by the commission in october 2002. annals of the icrp. 2003;33(1):1-206. 12. schauer da, linton ow. national council on radiation protection and measurements report shows substantial medical exposure increase 1. radiology. 2009;253(2):2936. 13. wakeford r, little m. risk coefficients for childhood cancer after intrauterine irradiation: a review. international journal of radiation biology. 2003;79(5):293-309. 14. wagner l, applegate k, radiology aco. acr practice guideline for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation. american college of radiology practice guideline. 2011. 15. berlin l. radiation exposure and the pregnant patient. ajr american journal of roentgenology. 1996;167(6):1377-9. 16. radiology aco. acr practice guideline for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation. reston, va: american college of radiology. 2008. 17. edwards m. implementation of the principle of as low as reasonably achievable (alara) for medical and dental personnel: recommendations of the national council on radiation protection and measurements; issued december 31, 19901990. 18. ctahrfetlloi r. health risks from exposure to low levels of ionizing radiation: beir vii phase 2. the national academies press; 2006. 19. damilakis j, perisinakis k, prassopoulos p, dimovasili e, varveris h, gourtsoyiannis n. conceptus radiation dose and risk from chest screen-film radiography. european radiology. 2003;13(2):406-12. 20. winer-muram ht, boone jm, brown hl, jennings sg, mabie wc, lombardo gt. pulmonary embolism in pregnant patients: fetal radiation dose with helical ct 1. radiology. 2002;224(2):487-92. 21. chandra v, dorsey c, reed ab, shaw p, banghart d, zhou w. monitoring of fetal radiation exposure during pregnancy. journal of vascular surgery. 2013;58(3):710-4. 22. shaw p, duncan a, vouyouka a, ozsvath k. radiation exposure and pregnancy. journal of vascular surgery. 2011;53(1):28s-34s. 23. sechopoulos i, suryanarayanan s, vedantham s, d’orsi this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. abushouk et al. 6 c, karellas a. weâăřeâăřl100jâăř05: radiation dose to tissues from mammography. medical physics. 2007;34(6):2606-. 24. valentin j. the 2007 recommendations of the international commission on radiological protection: elsevier oxford, uk; 2007. 25. raabe a, muller w-u. radiation exposure during pregnancy. neurosurgical review. 2008;31(3):351-2. 26. james dj, cardew p, warren-forward hm. determining the pregnancy status of patients before diagnostic nuclear medicine procedures: the australian experience. journal of nuclear medicine technology. 2011;39(3):2205. 27. james dj, cardew p, warren-forward hm. pregnancy screening strategies for potentially challenging patients before diagnostic nuclear medicine procedures: qualitative survey analysis. journal of nuclear medicine technology. 2013;41(4):292-8. 28. wilcox aj, baird dd, dunson d, mcchesney r, weinberg cr. natural limits of pregnancy testing in relation to the expected menstrual period. jama. 2001;286(14):1759-61. 29. no s. 478. european communities (medical ionising radiation protection) regulations. dublin stationery office, dublin. 2002. 30. amis es, butler pf, applegate ke, birnbaum sb, brateman lf, hevezi jm, et al. american college of radiology white paper on radiation dose in medicine. journal of the american college of radiology. 2007;4(5):272-84. 31. malviya s, d’errico c, reynolds p, huntington j, voepellewis t, pandit ua. should pregnancy testing be routine in adolescent patients prior to surgery? anesthesia & analgesia. 1996;83(4):854-8. 32. polaneczky m, o’connor k. pregnancy in the adolescent patient: screening, diagnosis, and initial management. pediatric clinics of north america. 1999;46(4):649-70. 33. thompson sk, goldman sm, shah kb, chen pc, wagner lk, corl fm, et al. acute non-traumatic maternal illnesses in pregnancy: imaging approaches. emergency radiology. 2005;11(4):199-212. 34. cohan r, matsumoto j, quagliano p. acr manual on contrast media. am coll radiol. 2012:59-63. 35. thomsen hs, morcos sk, almen t, bellin m-f, bertolotto m, bongartz g, et al. nephrogenic systemic fibrosis and gadolinium-based contrast media: updated esur contrast medium safety committee guidelines. european radiology. 2013;23(2):307-18. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction conclusion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 88 emergency (2016); 4 (2): 88-91 original research acute physiology and chronic health evaluation (apache) iii score compared to trauma-injury severity score (triss) in predicting mortality of trauma patients parvin darbandsar mazandarani1, kamran heydari1, hamidreza hatamabadi2, 3, parvin kashani1, yasin jamali danesh2* 1. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3. safety promotion and injury prevention research center, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: yasin jamali danesh; emergency department, imam hossein hospital, shahid madani avenue, tehran, iran. tel/fax: 00989125392962, email: yasindanesh@yahoo.com received: june 2015; accepted: august 2015 abstract introduction: more than 50 scoring systems have been published for classification of trauma patients in the field, emergency room, and intensive care settings, so far. the present study aimed to compare the ability of trauma injury severity score (triss) and acute physiology and chronic health evaluation (apache) iii in predicting mortality of intensive care unit (icu) admitted trauma patients. methods: this prospective cross-sectional study included icu admitted multiple trauma patients of imam hossein and hafte-tir hospitals, tehran, iran, during 2011 and 2012. demographic data, vital signs, mechanism of injury and required variables for calculating apache iii score and triss were recorded. the accuracy of the two models in predicting mortality of trauma patients was compared using area under the roc curve. results: 152 multiple trauma patients with mean age of 37.09 ± 14.60 years were studied (78.94% male). 48 (31.57%) cases died. for both apache iii and triss, predicted death rates significantly correlated with observed death rates (p < 0.0001). the mean age of dead patients was 37.21 ± 14.07 years compared to 37.03±14.96 years for those who survived (p = 0.4). the area under roc curve was 0.806 (95% ci: 0.663-0.908) for triss and 0.797 (95% ci: 0.652-0.901) for apache iii (p = 0.2). conclusion: based on the results of this study, both triss and apache models have the same accuracy in predicting mortality of icu admitted trauma patients. therefore, it seems that triss model would be more applicable in this regard because of its easier calculation, consideration of trauma characteristics, and independency of patient care quality. keywords: trauma severity indices; apache; injury severity score; multiple trauma cite this article as: darbandsar mazandarani p, heydari k, hatamabadi h, kashani p, jamali danesh y. acute physiology and chronic health evaluation (apache) iii score compared to trauma-injury severity score (triss) in predicting mortality of trauma patients. emergency. 2016; 4(2):88-91. introduction: trauma-scoring system converts the severity of injury into a number (1). scoring systems have been continuously developed to predict outcomes in patients with severe illness, improve resource allocation, and assist in clinical decision-making (2-4). moreover, the ability to predict the outcome of trauma (i.e., mortality) is perhaps the most fundamental use of injury severity scoring, which arises from the patients and their families' desires to know the prognosis (5). in recent years, several trauma scoring systems have been developed and validated for use in prediction of outcome, quality assurance and research (6). characterization of injury severity emerged in the 1950s. more than 50 scoring systems have been published for the classification of trauma patients in the field, emergency room, and intensive care settings, so far (5). there are three main groups of scoring systems for risk prediction in trauma patients. anatomical scores, which provide an overall score based on grades of multiple injuries; physiological scores are calculated by evaluating the physiological variables of the patient without considering the anatomical injuries; and comorbidity scores that assess both anatomical injury variables and physiological parameters to increase the predictive power (5, 7). trauma injury severity score (triss), the most widely used combined system, a this open-access article distributed under the terms of the creative commons attribution non-commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 89 emergency (2016); 4 (2): 88-91 provided improvements in the ability to predict outcome after trauma (1). triss method had its inception in 1981, followed by further consolidation of the concept with the major trauma outcome study. this method provided improvements in the ability to predict trauma outcome, especially mortality, and therefore acquired worldwide popularity despite its limitations being recognized later (1). the need to collect information on patients in the intensive care units (icu) and use that information to improve outcomes, led to the development of acute physiology, age, and chronic health evaluation system, known by its acronym apache (8). in 1991 apache iii was introduced, which consisted of a set of equations for predicting hospital mortality, icu mortality, hospital length of stay, icu length of stay, risk of active treatment, duration of mechanical ventilation, and therapeutic intervention scoring system (tiss) (8). practitioners do not widely accept apache iii, partly because it is proprietary and expensive. in addition, its accuracy needs to be validated in trauma patients (1). therefore, the aim of this research was to assess the ability of triss and apache iii in predicting mortality rate of multiple trauma patients. methods: study design and setting this prospective cross-sectional study included 152 multiple trauma patients admitted to the icu of imam hossein and hafte-tir hospitals, tehran, iran, in 2011 and 2012. patients younger than 14 years old and those who died within less than 4 hours of arrival in icu were excluded. each patient’s demographic data, vital signs (systolic blood pressure (sbp), heart rate, respiratory rate (rr)), mechanism of injury, level of consciousness (based on glasgow coma scale (gcs)), and other required variables for calculation of triss and apache iii scores were recorded. triss combines physiologic (revised trauma score: rts) and anatomic (injury severity score: iss) components of injury with age (9). data collected on admission to the emergency department, were used for calculation of rts and iss. the protocol of this study was approved by the ethical committee of shahid beheshti university of medical sciences. the authors adhered to confidentiality of patient information during the study period. definitions: rts: rts is the sum of the coded value multiplied of gcs, sbp, and rr (6). it is calculated by the following formula (6): rts = 0.9368 gcs +0.7326 sbp +0.2908 rr rts values range from 0 to 7.84. iss: iss is an index of severity and location of anatomy injury. it correlates reasonably well with mortality probability, and is calculated by adding the square of each of the coded values of the three most severely injured body regions and has a range from 0 to 75. rts, iss, and patient age, were placed in a logistic transformation to yield a survival probability (ps) ranging from 0 to 1 and death probability (pod) is 1-ps. apache: apache iii scores were calculated for each patient from data collected during the first 24 hours of icu admission. the apache iii score consists of several parts including the primary reason for icu admission, age, sex, race, preexisting comorbidities, and location prior to icu admission (10). the range of apache iii score is from 0 to 299 points. statistical analysis data were analyzed using spss 21 software. continuous variables were expressed as mean ± standard deviation and categorical ones were expressed in frequencies and percentages. the area under the roc curve for each scale was used to compare the accuracy of the studied models (11). chi square and fisher exact test were used to compare categorical measures and student‘s t-test was used to compare means. p > 0.05 was considered as statistically non-significant. results: 152 multiple trauma patients were studied. 120 of them were male (78.94%) and 32 (21.05%) were female. mean age was 37.09 ± 14.60 years (range: 16-70 years). the most common cause of trauma was traffic accidents involving: pedestrian-car accidents (23.36%), car-car accidents (17.76%), motorcycle-car accidents (14.47%), car rollover (11.84%), pedestrianmotorcycle accidents (9.21%) and motor rollover (2.06%). the others were falling down (16.44%), assault (3.64%) and hanging (1.31%). in the end, 48 (31.57%) died (75% male). for both apache iii and triss predicted death rates significantly correlated with observed death rates (p < 0.0001). the mean age of dead patients was 37.21 ± 14.07 years compared to 37.03±14.96 years for those who survived (p = 0.4). table 1 compares alive and dead patients’ trauma severity based on iss, rts, triss, and apache iii scores. the area under roc curve was 0.806 (95% ci: 0.663-0.908) for triss and 0.797 (95% ci: table 1: comparison of alive and dead patients’ trauma severity based on iss, rts, triss and apache iii scores scores* alive (n=104) dead (n=48) p-value injury severity score (iss) 37.88 ± 12.77 50.69 ± 11.61 <0.0001 revised trauma score (rts) 6.71 ± 1.18 5.52 ± 1.33 <0.0001 trauma injury severity score (triss) 25.36 ± 24.80 56.01 ± 32.30 <0.0001 apache iii 41.92 ± 22.67 70.04 ± 24.48 <0.0001 *mean ± standard deviation; apache: acute physiology and chronic health evaluation. this open-access article distributed under the terms of the creative commons attribution non-commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com darbandsar mazandarani et al 90 0.652-0.901) for apache iii (figure 1 and 2, p = 0.2). the best cut-off points for mortality prediction were 13.2 (sensitivity = 76.52%; specificity = 95.65%) and 51 (sensitivity = 73.91%; specificity = 78.26%) for triss and apache iii, respectively. discussion: according to results of our study, both triss and apache iii scores accurately predict mortality of multiple trauma patients. the area under roc curve for triss and apache iii were not significantly different (p = 0.2), which means they are equally accurate in this regard. there are several scoring systems and prognostic models in general use for outcome prediction in hospitalized patients. the rationale behind using these scales commonly, is to rate illness severity to yield comparison between patients (12, 13). objective risk estimates are particularly important in the high-cost, emotional, and technologically demanding environments of icu. because of the high costs of icu, precise quality assurance and utilization management strategies are essential (10). outcome prediction systems have become key tools to evaluate the care quality and the icu performance. triss and apache iii are two systems currently in common use for measuring the condition of icu patients (14). triss has been used in quality assurance programs for evaluating trauma care and identifying unexpected deaths (15, 16). it has been widely used in outcome prediction of trauma patients. the basis for the development of apache is the hypothesis that the severity of acute diseases can be measured by quantifying the degree of abnormality from multiple physiologic variables (17). the development of apache iii was based on the association between acute changes in a patient’s physiologic balance and shortterm risk of death (10). apache iii is widely used to assess illness severity of patients admitted to icu and to compare risk-adjusted outcomes between icus. age, level of consciousness, biochemical, physiological, and chronic health variables in the first 24 hours of icu admission are incorporated into the score (18). in line with the findings of the present study, thanapaisal and saksaen declared the ability of triss system in predicting mortality in intensive care unit (icu) trauma patients (18). safavi and honarmand found that apache iii provides more information than apache ii regarding determining factors of trauma severity (19). knaus et al. found that the overall explanatory power of apache iii on the first day of icu treatment (r2 = 041 and roc = 0.90) compares well to that of previous versions of apache (10). however, in contrast to our results, some showed that trauma score or iss did not predict survival (20). vassar et al. evaluated the ability of triss to predict mortality in 1,000 icu admitted trauma patients and reported that triss overestimates mortality in patients whose predicted risk ranges were high (21). likewise, wong et al. (1996) found that triss was a poor predictor of hospital death risk among icu admitted trauma patients (22). it seems that, triss has several advantages over apache for application on trauma patients. first, triss has a detailed description of severity and location of anatomic injury, but apache does not include an assessment of trauma mechanism or the specific anatomical injury. second, apache assesses the most abnormal physiologic data in the first 24 hours and is highly dependent on the quality of care given to the patient. third, triss is easier to calculate than apache. the results of our study figure 1: receiver operating characteristic (roc) curve for triss model. figure 2: receiver operating characteristic (roc) curve for apache iii model. 0 20 40 60 80 100 0 20 40 60 80 100 100-specificity s e n si ti v it y 0 20 40 60 80 100 0 20 40 60 80 100 100-specificity s en si ti vi ty this open-access article distributed under the terms of the creative commons attribution non-commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 91 emergency (2016); 4 (2): 88-91 give us the support to use both combined scores for mortality prediction in critically ill trauma patients. however, the simplicity of triss calculation makes it easier and more applicable than apache iii (23, 24). conclusion: based on the results of this study, both triss and apache models have the same accuracy in predicting mortality of trauma patients. therefore, it seems that triss model would be more applicable in this regard because of its easier calculation, consideration of trauma characteristics, and independency of patient care quality. acknowledgment: the authors wish to thank all the staff of imam hossein and hafte-tir hospitals. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. chawda m, hildebrand f, pape hc, giannoudis pv. predicting outcome after multiple trauma: which scoring system? injury. 2004;35(4):347-58. 2. balestreri m, czosnyka m, chatfield d, et al. predictive value of glasgow coma scale after brain trauma: change in trend over the past ten years. j neurol neurosurg psychiatry. 2004;75(1):161-2. 3. forouzanfar mm, safari s, niazazari m, et al. clinical decision rule to prevent unnecessary chest x‐ray in patients with blunt multiple traumas. emerg med australas. 2014;26(6):561-6. 4. shojaee m, faridaalaee g, yousefifard m, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chin j traumatol. 2014;17(1):19-24. 5. hamed g, omar e, el-bary aa. the utility of trauma scoring systems in outcome prediction of critical patients. med j cairo univ. 2010;78(2). 6. thanapaisal c, saksaen p. a comparison of the acute physiology and chronic health evaluation (apache) ii score and the trauma-injury severity score (triss) for outcome assessment in srinagarind intensive care unit trauma patients. j med assoc thai. 2012;95(11):s25-s33. 7. köseoğlu z, kuvvetli a, kösenli o, et al. increased nutritional risk in major trauma: correlation with complications and prolonged length of stay. ulus travma acil cerrahi derg. 2011;17(6):521-4. 8. zimmerman je, wagner dp, draper ea, wright l, alzola c, knaus wa. evaluation of acute physiology and chronic health evaluation iii predictions of hospital mortality in an independent database. crit care med. 1998;26(8):1317-26. 9. champion hr, sacco wj, carnazzo aj, copes w, fouty wj. trauma score. crit care med. 1981;9(9):672-6. 10. knaus wa, wagner dp, draper ea, et al. the apache iii prognostic system. risk prediction of hospital mortality for critically ill hospitalized adults. chest. 1991;100(6):1619-36. 11. champion hr, sacco wj, copes ws, gann ds, gennarelli ta, flanagan me. a revision of the trauma score. j trauma acute care surg. 1989;29(5):623-9. 12. blackburn g, benotti p, bistrian b, et al. nutritional assessment and treatment of hospital malnutrition. transfus med hemother. 1979;6(4):238-50. 13. boyd o, jackson n. clinical review: how is risk defined in high-risk surgical patient management. crit care. 2005;9(4):390-6. 14. zali ar, seddighi as, seddighi a, ashrafi f. comparison of the acute physiology and chronic health evaluation score (apache) ii with gcs in predicting hospital mortality of neurosurgical intensive care unit patients. glob j health sci. 2012;4(3):179-84. 15. boyd cr tm, copes ws. evaluation trauma care: the triss method. j trauma. 1987;27(4):370-8. 16. champion hr, copes ws, sacco wj, lawnick mm, keast sl, frey cf. the major trauma outcome study: establishing national norms for trauma care. j trauma acute care surg. 1990;30(11):1356-65. 17. dalgic a, ergungor fm, becan t, elhan a, okay o, yuksel bc. the revised acute physiology and chronic health evaluation system (apache ii) is more effective than the glasgow coma scale for prediction of mortality in head-injured patients with systemic trauma. ulus travma acil cerrahi derg. 2009;15:4538. 18. mcnamee jj, pilcher dv, bailey mj, moore ec, cleland hj. mortality prediction and outcomes among burns patients from australian and new zealand intensive care units. crit care resusc. 2010;12:196-201. 19. safavi m, honarmand a. comparison of infection probability score, apache ii, and apache iii scoring systems in predicting need for ventilator and ventilation duration in critically ill patients. arch iran med. 2007;10(3):354-60. 20. rocca b, martin c, viviand x, bidet p, saint-gilles hl, chevalier a. comparison of four severity scores in patients with head trauma. j trauma acute care surg. 1989;29(3):299305. 21. vassar mj, wilkerson cl, duran pj, perry ca, holcroft jw. comparison of apache ii, triss, and a proposed 24-hour icu point system for prediction of outcome in icu trauma patients. j trauma acute care surg. 1992;32(4):490-500. 22. wong dt, barrow pm, gomez m, mcguire gp. a comparison of the acute physiology and chronic health evaluation (apache) ii score and the trauma-injury severity score (triss) for outcome assessment in intensive care unit trauma patients. crit care med. 1996;24(10):1642-8. 23. rabbani a, moini m, rabbani a, moini m. application of" trauma and injury severity score" and" a severity characterization of trauma" score to trauma patients in a setting different from" major trauma outcome study. arch iran med. 2007;10(3):383-6. 24. siritongtaworn p, opasanon s. the use of trauma scoreinjury severity score (triss) at siriraj hospital: how accurate is it? j med assoc thai. 2009;92(8):1016-21. archives of academic emergency medicine. 2023; 11(1): e48 or i g i n a l re s e a rc h pre-hospital prognostic factors of 30-day survival in sepsis patients; a retrospective cohort study thongpitak huabbangyang1, rossakorn klaiangthong1∗, fahsai jaibergban1, chanathip wanphen2, thanakorn faikhao2, passakorn banjongkit2, ratchaporn kuchapan2 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. received: may 2023; accepted: june 2023; published online: 13 july 2023 abstract: introduction: according to excising findings, if the emergency management system (ems) operation will be developed, the survival outcome of sepsis patients might improve. this study aimed to evaluate the pre-hospital associated factors of survival in sepsis patients. methods: this retrospective cohort study was conducted on patients diagnosed with sepsis, coded with the thailand emergency medical triage protocol and criteria-based dispatch symptom group 17. information on the 30-day survival rate of patients was obtained from the electronic medical records. pre-hospital factors associated with 30-day survival were analyzed using univariate and multivariate logistic regression analyses and were reported using odds ratio (or) with 95% confidence interval (ci). results: 300 patients diagnosed with sepsis were enrolled. among them, 232 (77.3%) survived within 30 days. non-survived cases had significantly older age (p = 0.019), lower oxygen saturations (92.5% vs. 95.0%; p = 0.003), higher heart rate (p = 0.001), higher respiratory rate (p < 0.001), lower level of consciousness (p < 0.001), higher disease severity based on qsofa score (p = 0.001), and higher need for invasive airway management (p = 0.001) and supplementary oxygen (p = 0.001). the survival rate improved by 3.5% with every 1% increase in pre-hospital oxygen saturation (adjusted or = 1.035, 95% ci: 1.005–1.066, p = 0.020) and the survival probabilities of patients who responded to voice (adjusted or = 0.170, 95% ci: 0.050–0.579, p = 0.005), those who responded to pain (adjusted or = 0.130, 95% ci: 0.036–0.475, p = 0.002), and those who were unresponsive (adjusted or = 0.086, 95% ci: 0.026–0.278, p-value < 0.001) were lower than patients who were alert. conclusion: the 30-day survival rate of patients with sepsis managed by the ems team was 77.3%. pre-hospital oxygen saturation and level of consciousness were associated with the survival of patients with sepsis who were managed in the pre-hospital setting. keywords: emergency medical services; emergency treatment; sepsis; survival cite this article as: huabbangyang t, klaiangthong r, jaibergban f, wanphen c, faikhao t, banjongkit p, kuchapan r. pre-hospital prognostic factors of 30-day survival in sepsis patients; a retrospective cohort study. arch acad emerg med. 2023; 11(1): e48. https://doi.org/10.22037/aaem.v11i1.2029. 1. introduction sepsis is a leading cause of death worldwide. its incidence rate is approximately 48.9%, which is lower than that of accident-related mortality. based on previous studies worldwide, variations in the reported incidence of sepsis are caused by differences in disease definitions, study periods, types of data collected, patient groups, and public health systems in each area (1). a study in the united states of amer∗corresponding author: rossakorn klaiangthong; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok 10400, thailand. tel: +66 2244-3000, email: rossakorn@nmu.ac.th, orcid: https://orcid.org/0000-00025846-5754. ica revealed that the mortality rate of sepsis decreased from 28.6%–45.0% in 2001 to 12.3% in 2019, due to improvement in medicine and public health within 20 years (2, 3). in addition, a study with long-term follow-up found that the mortality rate of patients with severe sepsis or those with delayed evaluation and treatment is higher (3). a previous metaanalysis on studies from seven countries revealed that the mortality rate of sepsis was 17.0% and the mortality rate of severe sepsis was higher, at 26.0% (4). research on southeast asian countries, including thailand, malaysia, and vietnam, reported that the 28-day mortality rates of sepsis were 7.0% in patients without signs of organ dysfunction and 47.0% in those with at least four signs (5). according to the index statistics on the rate of mortality due to sepsis in the ministry this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 2 of public health hospitals of thailand, more than 452,480 patients presented with sepsis, and there were over 153,324 deaths recorded from 2018 to 2022 (6). based on the surviving sepsis campaign in 2016 guidelines, sepsis is an actual medical emergency condition (7). it commonly requires emergency medical service (ems) in the prehospital setting (8). therefore, patients with sepsis should be managed during the pre-hospital period, and the window for the hour-1 sepsis bundle must be reduced. sepsis can be screened and diagnosed in the pre-hospital setting. thus, patients can receive treatment more quickly, which can consequently increase the survival rate (9, 10). if the ems team can immediately initiate a provisional diagnosis of sepsis, perform appropriate evaluation, provide treatment, and monitor vital signs continuously at the scene and during transportation, the survival rate can increase (11). a study in brazil showed that oxygen depletion and sequential organ failure assessment (sofa) score of ≥3 was associated with a lower survival rate in sepsis patients (12). a study that aimed to evaluate the epidemiology of sepsis in the pre-hospital context found that an abnormal respiratory rate and decreased level of consciousness are significantly associated with a high mortality rate (13). based on the above-mentioned points, this study aimed to assess the 30-day survival rate and its pre-hospital associated factors in patients with sepsis whose managements were started by ems in the pre-hospital setting in thailand. 2. methods 2.1. study design and settings this retrospective cohort study was conducted at the vajiraems (v-ems) unit, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand to evaluate the pre-hospital associated factors of survival in sepsis patients whose managements were started by ems, from january 1, 2019 to october 31, 2022. the v-ems unit is the leading ems center among nine zone areas in bangkok, dispatched from erawan center, bangkok, networking with both public and private hospitals, with six hospitals in the responsible area, which was 50 square kilometers and a population of 500,000 (14, 15). the ems team of the v-ems unit comprises at least three staff, which include paramedics or emergency nurse practitioners (enps), which act as the operation team leader, and emergency medical technicians. during each operation, the paramedics or enps can operate under offand on-line medical protocols based on the orders of emergency physicians. in the study area, the sepsis management guidelines include the use of the quick sepsis-related organ failure assessment (qsofa) score in the pre-hospital setting. patients should have a score of at least 2 for the following parameters: respiratory rate (at least 22 cycles/min), systolic blood pressure (approximately 90 mmhg), and glasgow coma scale (gcs) score (13) or decreased level of consciousness, and sepsis diagnosis. a diagnosis of sepsis is made based on the presence of at least two items of systemic inflammatory response syndrome (sirs) criteria (16). according to the offline protocol for patients with sepsis, paramedics or enps should start oxygen supplementation with a cannula or mask with a reservoir bag and endotracheal intubation according to pre-hospital guidelines. oxygen saturation should be maintained at ≥94%. venous catheterization must be performed to administer at least 30 ml/kg of crystalloid solutions (e.g., lactated ringer’s solution [lrs] and acetar) if there are no contraindications such as crepitation in both lungs and edema in both legs (systolic blood pressure maintained at ≥90 mmhg). moreover, reassessment is performed after every administration of 300–500 ml of fluid. 2.2. participants adult patients with final diagnosis of sepsis, symptom group 17red1 – 17red9, dispatched to v-ems, aged more than 18 years, coded with thailand emergency medical triage protocol and cbd symptom group 17, which is sepsis or septic shock and transported to emergency department, were enrolled in the study. patients who refused treatment or transportation to the hospital, those with incomplete or missing data, and those receiving end-of-life or palliative care were excluded from the analysis. 2.3. data collection the data of patients finally diagnosed with sepsis or septic shock were collected from the ems patient care report, which is a record of advanced ems operation. this form comprised data on ems operation units, patients, and all treatments provided by the ems teams. all data were recorded by dispatchers and paramedics or enps at the scene. further, these data were a part of remuneration for the ems operation units. data on 30-day survival were extracted from the electronic medical records of vajira hospital. we collected information including demographic and clinical characteristics of the participants (such as gender; age; underlying disease; location; sepsis category; pre-hospital systolic and diastolic blood pressures, heart and respiratory rates, oxygen saturation, body temperature, level of consciousness [alert, responds to pain, responds to voice, and unresponsive], airway management, oxygen supplementation with a cannula, mask with a reservoir bag, and bag valve mask, fluid supplementation, and blood glucose level; qsofa score; response time; on-scene time; distance from the base station to the scene; and distance from the scene to the hospital, and data on 30-day survival outcome), which were reviewed by the primary investigator from the electronic medical records. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e48 2.4. outcome measures the primary outcome was 30-day survival. 2.5. definition of terms sepsis is a life-threatening condition caused by the host’s abnormal response to infection. septic shock is defined as a systolic blood pressure of <90 mmhg and arrhythmia with a heart rate of >100 beats/min (17). in our study area, paramedics or enps suspect infection in patients with fever or a history of fever and those with symptoms indicative of infection or organ dysfunction. further, they assess qsofa score. if the score is at least 2, a diagnosis of sepsis is made, and the management guidelines for patients with sepsis or septic shock can be applied immediately at the scene. the thailand emergency medical triage protocol and cbd severity code was used at the scene. it utilizes data obtained by evaluating the situation and symptoms of patients at the scene. further, it uses 26 symptom groups. symptom group 17 is defined as a diagnosis of sepsis or septic shock using 17 code red 1–9. response time (min) was defined as the duration from emergency call to ambulance arrival at the scene. on-scene time (min) was defined as the duration from ambulance arrival at the scene to departure from the scene. thirty-day survival was defined as the survival of patients with sepsis or septic shock (rc code 17 red) who were managed by ems in the pre-hospital setting and evaluated within 30 days (from day 1 [service day] to day 30). 2.6. sample size the sample size was estimated using the formula for infinite population proportion. a normal curve was defined as a pvalue of 0.05 and an error rate of 4%. the proportion of patients was based on a previous study. the 30-day survival rate of patients with sepsis managed by ems at the pre-hospital setting was 89.3% (10). the sample size was at least 230. thereafter, 288 patients were added based on the following formula: nnew = 230/(1 0.20). hence, the final sample size was 300. simple random sampling was performed to obtain a sample including patients diagnosed with sepsis in the prehospital setting and dispatched to the v-ems unit. 2.7. statistical analysis a descriptive analysis was performed to examine variable distribution. continuous variables were expressed as mean ± standard deviation or median and inter-quartile range (iqr) and categorical variables as frequencies and percentages. between-group differences were evaluated using the independent t-test or the mann–whitney u test for numeric variables and the chi-square test or the fisher’s exact test for categorical variables. the 30-day survival rate of patients with sepsis whose management was started at the pre-hospital setting was expressed as frequency distribution and percentage. to evaluate factors associated with the 30-day survival of patients with sepsis managed in the pre-hospital setting, crude analysis was performed using the chi-square test or the fisher’s exact test based on data appropriateness and multivariate logistic regression analysis, the result were reported as odds ratio (or) and 95% confidence interval (ci). the statistical package for the social sciences software for windows, version 28.0 (ibm spss statistics for windows, version 26.0; ibm corp., armonk, ny, the usa) was used. a pvalue of <0.05 was considered statistically significant. 2.8. ethical statement this study was conducted in accordance with the 1975 declaration of helsinki and its 2000 revised version. it was approved by the institutional review board of the faculty of medicine vajira hospital, navamindradhiraj university (coa no. 220/2565). the need for informed consent was waived due to the retrospective nature of the study and anonymity of all patient data. 3. results 3.1. baseline characteristics of the participants 300 patients diagnosed with sepsis were enrolled. among them, 232 (77.3%) survived within the 30 days of follow-up. the mean age of patients was 73.40 ± 16.00 years (53.7% male). table 1 compares the baseline characteristics of studied cases between survived and non-survived cases. the mean ages of the survivors and non-survivors were 72.34 ± 16.51 and 77.01 ± 13.63 years, respectively (p = 0.019). the two groups had similar conditions regarding gender distribution (p = 0.488), underlying diseases (p = 0.331), location of residence (p = 1.000), disease category (p = 0.167), prehospital systolic blood pressure (p = 0.111), diastolic blood pressure (p = 0.389), body temperature (p = 0.389), blood glucose (p = 0.359), the median response time (p = 0.688), the median on-scene times (p = 0.925), the median distance from the base station to the scene (p = 0.973), the median distance from the scene to the hospital (p = 0.442), and volume of hydration therapy in pre-hospital setting (p = 0.098). non-survived cases had significantly lower oxygen saturations (92.5% vs. 95.0%; p = 0.003), higher heart rate (p = 0.001), higher respiratory rate (p < 0.001), lower level of consciousness (p < 0.001), higher disease severity based on qsofa score (p = 0.001), and higher need for invasive airway management (p = 0.001) and supplementary oxygen (p = 0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 4 table 1: comparing the baseline characteristics of the participants between survivors and non-survivors factors survivors (n = 232) non-survivors (n = 68) p-value age (years) mean ± sd 72.34 ± 16.51 77.01 ± 13.63 0.019t gender male 122 (52.6) 39 (57.4) 0.488c female 110 (47.4) 29 (42.6) underlying disease no 83 (35.8) 20 (29.4) 0.331c yes 149 (64.2) 48 (70.6) location home 225 (97.0) 66 (97.1) 1.000f public 7 (3.0) 2 (2.9) disease category sepsis 203 (87.5) 55 (80.9) 0.167c septic shock 29 (12.5) 13 (19.1) pre-hospital vital signs sbp (mmhg) 129.95 ± 31.80 122.79 ± 34.82 0.111t dbp (mmhg) 73.29 ± 19.69 73.90 ± 27.12 0.839t heart rate (/min) 102.22 ± 21.9 112.66 ± 25.71 0.001t respiratory rate (/min) 25.30 ± 6.67 28.82 ± 8.06 <0.001t oxygen saturation (%) 95 (92–98) 92.5 (81–97) 0.003m body temperature (°c) 37.79 ± 1.05 37.85 ± 0.99 0.671t blood glucose level (mg/dl) 144 (115–181) 145 (119.5–190.5) 0.359m pre-hospital level of consciousness alert 97 (41.8) 6 (8.8) <0.001c respond to pain 49 (21.1) 32 (47.1) respond to voice 56 (24.1) 13 (19.1) unresponsive 30 (12.9) 17 (25.0) qsofa score < 2 118 (50.9) 19 (27.9) 0.001c ≥ 2 114 (49.1) 49 (72.1) ems management response time (min) 12 (7–16) 12 (8.5–16.5) 0.688m on-scene time (min) 16 (12–24) 17 (13–23) 0.925m base station to the scene (km) 3 (2–5) 4 (2–5) 0.973m scene to the hospital (km) 3 (2–5) 4 (2–6) 0.442m pre-hospital airway management no 220 (94.8) 55 (80.9) 0.001f endotracheal tube 10 (4.3) 7 (10.3) oropharyngeal airway 2 (0.9) 5 (7.4) nasopharyngeal airway 0 (0.0) 1 (1.5) pre-hospital oxygen supplementation no 115 (49.6) 16 (23.5) 0.001c cannula 62 (26.7) 21 (30.9) mask with a reservoir bag 47 (20.3) 25 (36.8) bag valve mask 8 (3.4) 6 (8.8) pre-hospital fluid supplementation no 83 (35.8) 14 (20.6) 0.098f normal saline 71 (30.6) 26 (38.2) ringer lactate 73 (31.5) 27 (39.7) 10% dn/2 5 (2.2) 1 (1.5) data are presented as mean ± standard deviation (sd), number (%), or median (interquartile range). sbp: systolic blood pressure; dbp: diastolic blood pressure ems: emergency medical services; qsofa: quick sepsis-related organ failure assessment. p-value corresponds to the tindependent samples t-test, mmann–whitney u test, cchi-square test, or ffisher’s exact test. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e48 table 2: multivariate logistic regression analysis of associated factors of survival in sepsis patients factors oradj1 95% ci p-value age (years) 0.980 (0.959–1.002) 0.080 prehospital vital sign heart rate (beats/min) 0.988 (0.973–1.004) 0.143 respiration rate (cycles/min) 0.976 (0.926–1.029) 0.372 oxygen saturation (%) 1.035 (1.005–1.066) 0.020 prehospital level of consciousness alert 1.000 reference responds to voice 0.170 (0.050–0.579) 0.005 responds to pain 0.130 (0.036–0.475) 0.002 unresponsive 0.086 (0.026–0.278) <0.001 qsofa score <2 0.531 (0.228–1.238) 0.143 ≥2 1.000 reference prehospital airway management no 1.000 reference 0.383 yes 0.621 (0.213–1.812) prehospital oxygen supplementation no 1.000 reference 0.362 yes 0.697 (0.321–1.513) prehospital fluid supplementation no 1.000 reference 0.660 yes 0.843 (0.395–1.8) abbreviations: or, odds ratio; oradj, adjusted odds ratio; ci, confidence interval; na, not applicable; qsofa: quick sepsis-related organ failure assessment. variable with a p-value of <0.050 in the univariate analysis were included in the multivariate analysis. 1adjusted odds ratio estimated using the multiple logistic regression model. 3.2. multivariate analysis of factors associated with 30-day survival age, qsofa score, and pre-hospital heart and respiratory rate, oxygen saturation, level of consciousness, airway management, and oxygen supplementation were significantly associated with 30-day survival of sepsis patients based on the univariate analysis. table 2 shows the findings of multivariate logistic regression analysis of factors associated with 30-day survival. based on this analysis pre-hospital oxygen saturation level and level of consciousness were found to be the independent predictors of 30-day survival in sepsis patients. with every 1% increase in pre-hospital oxygen saturation, the survival rate improved by 3.5% (adjusted or = 1.035, 95% ci: 1.005–1.066, p = 0.020). the survival probabilities of patients who responded to voice in the pre-hospital settings, those who responded to pain, and those who were unresponsive were 0.170 (adjusted or = 0.170, 95% ci: 0.050–0.579, p = 0.005), 0.130 (adjusted or = 0.130, 95%ci: 0.036–0.475, p = 0.002), and 0.086 (adjusted or = 0.086, 95%ci: 0.026–0.278, p < 0.001) times lower than patients who were alert. 4. discussion the 30-day survival rate of patients diagnosed with sepsis or septic shock was 77.3%. this finding is consistent with that of a previous study in the netherlands. that is, the survival rate of patients with sepsis who received ems care was 79.0%, and the mean hospitalization period was 13.5 days (18). another study revealed that the overall 30-day survival of patients with sepsis and septic shock in the emergency department of mexico was 83.07%. although the survival rate decreased in the septic shock group (19), the 28-day survival rate of patients with sepsis was 53.0% in southeast asian countries, such as malaysia (5). according to previous research, if the ems operation is performed, the survival outcome of patients with sepsis might improve. further, assistance can be provided in various processes, which include the development of appropriate and convenient pre-hospital sepsis screening tools, fluid replacement, and antibiotic initiation, which might improve patient survival (20). nevertheless, a previous study showed that the mortality rate and length of hospital stay are different in survived cases (21). the current study showed that pre-hospital oxygen saturation and level of consciousness were associated with 30-day survival in patients with sepsis managed by ems. this finding is consistent with that of a previous study on the ems of a tertiary care institution in north-western india. results showed that oxygen saturation was a predictive factor of survival outcome in patients with sepsis and septic shock. moreover, patients with hypoxia had a higher mortality rate (average: 26.92%) than those with normoxia (22). a study conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 6 ducted in the intensive care unit showed that patients who were treated at the intensive care unit and survived sepsis had a higher oxygen saturation level than those who did not survive. moreover, patients with sepsis should receive appropriate oxygen therapy to improve survival outcome (23). with every 1% increase in pre-hospital oxygen saturation, the survival rate improved by 3.5%. therefore, appropriate and adequate pre-hospital oxygen supplementation was recommended. further, indirect noninvasive oxygen delivery, which can be easily performed by the emergency medical staff, must be considered. that is, capillary refill time and cyanosis assessment is required to improve the quality of management in patients with sepsis who were managed in the pre-hospital setting. this finding was consistent with the latest standard guidelines for managing patients with sepsis or septic shock. that is, patients with septic shock must undergo regular capillary refill time assessment (24). patients with sepsis who had low pre-hospital level of consciousness might have a significantly lower survival rate. this finding was similar to that of a previous observational study using gcs as a predictive tool for survival rate, which showed that patients with decreased level of consciousness had a significantly higher mortality rate (25). moreover, it is comparable to two studies in the emergency departments. the first study reported a high 30-day mortality rate after sepsis diagnosis at the emergency department among patients with a low level of consciousness. unresponsive patients could have a higher mortality rate than responsive patients (26). the second study found that an altered mental state could classify the mortality rate in septic patients in the emergency department at 28 days and could be a predictor of survival (27). based on the standard guidelines for managing patients with sepsis in the pre-hospital setting, the ems staff should emphasize and focus on assessing the level of consciousness using either the gcs or the avpu (alert, voice, pain, unresponsive) scale, whichever is appropriate in each area. proper neurological assessment and maintenance of level of consciousness at the scene and during hospital transport were important in improving survival outcomes in patients with sepsis. regarding suggestions for future research, since the present study only focused on pre-hospital factors affecting septic patients’ survival at 30 days, the future research should study factors affecting the patients’ survival in pre-hospital and hospital, as well as definitive care contexts, such as emergency department or intensive care unit. for health managers and policymakers, the present study presented factors important for pre-hospital management by ems team, which affected 30-day survival of septic patients and sepsis. this type of study is substantially necessary for policy making in pre-hospital management system for specific diseases that are time-sensitive and have pretty high mortality rates, such as sepsis. 5. study limitations the current study had several limitations. first, it was retrospective in nature and was conducted at a single center with two data sources. although neutrality was tried to be maintained in every way, there might still be a risk for potential selection bias, such as biases from population selection of patients with sepsis and septic shock, selection of qsofa score in pre-hospital diagnosis of sepsis, which were believed that these potential biases did not have a significant impact on results important for septic patients’ survival. second, some confounding factors associated with outcomes of interest might not have been evaluated. only data on pre-hospital management were analyzed. nonetheless, data from the emergency department or intensive care unit in the hospital should also be considered and analyzed because they might affect survival. third, only patients diagnosed with sepsis or septic shock who were transported to the emergency department of vajira hospital were analyzed. however, patients brought to the emergency departments of other hospitals should also be considered because the capability of a hospital’s emergency department can affect survival outcome. fourth, the study was conducted in a single ems unit, which was an academic center. the present study results might not be generalizable. further studies are needed to test the external validity of the present study results. finally, in the study area, only qsofa was used as a screening tool. nevertheless, bias was tried to be reduced from the screening tool by using final diagnosis at ed as inclusion criteria, which is in accordance with the surviving sepsis campaign: international guidelines for the management of sepsis and septic shock 2021. the application of qsofa was not recommended for screening patients with sepsis and septic shock. however, in the study area, only qsofa was used, and an accurate provisional diagnosis by paramedics or enps at the scene could substantially affect decision-making. 6. conclusion the 30-day survival rate of patients with sepsis managed by the ems team was substantially high (77.3%). pre-hospital oxygen saturation and level of consciousness were associated with the survival of patients with sepsis who were managed in the pre-hospital setting. hence, guidelines on the prehospital management of sepsis, which emphasize the need to evaluate oxygen saturation and level of consciousness during hospital transport, should be developed. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e48 7. declarations 7.1. acknowledgments the authors are grateful to the navamindradhiraj university research fund for publication. we would like to thank the paramedics at v-ems, faculty of medicine vajira hospital, navamindradhiraj university, for facilitating data collection and access in the present study, gawin tiyawat, md., chief of department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, and chunlanee sangketchon, md., deputy dean of faculty of science and health technology, navamindradhiraj university, for support and suggestions in the research development and aniwat berpan, md. for suggestions on english for the present study. 7.2. conflict of interest the authors have no conflicting interests to declare. 7.3. funding and support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution conceptualization: thongpitak huabbangyang, chanathip wanphen, thanakorn faikhao, passakorn banjongkit and ratchaporn kuchapan; methodology: thongpitak huabbangyang, rossakorn klaiangthong and fahsai jaibergban; software: thongpitak huabbangyang; validation: thongpitak huabbangyang; formal analysis: thongpitak huabbangyang; investigation: thongpitak huabbangyang; resources: thongpitak huabbangyang, chanathip wanphen, thanakorn faikhao, passakorn banjongkit and ratchaporn kuchapan; data curation: thongpitak huabbangyang; writing – original draft: thongpitak huabbangyang; writing review & editing: thongpitak huabbangyang; visualization: thongpitak huabbangyang, rossakorn klaiangthong and fahsai jaibergban; supervision: thongpitak huabbangyang; project administration: thongpitak huabbangyang; funding acquisition: thongpitak huabbangyang. all authors read and approved the final version of manuscript. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. 7.6. using artificial intelligence chatbots none. references 1. rudd ke, johnson sc, agesa km, shackelford ka, tsoi d, kievlan dr, et al. global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the global burden of disease study. lancet. 2020;395(10219):20011. 2. stoller j, halpin l, weis m, aplin b, qu w, georgescu c, et al. epidemiology of severe sepsis: 2008-2012. j crit care. 2016;31(1):58-62. 3. alberti c, brun-buisson c, goodman sv, guidici d, granton j, moreno r, et al. influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients. am j respir crit care med. 2003;168(1):77-84. 4. fleischmann c, scherag a, adhikari nk, hartog cs, tsaganos t, schlattmann p, et al. assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. am j respir crit care med. 2016;193(3):259-72. 5. lie kc, lau c-y, van vinh chau n, west te, limmathurotsakul d. utility of sofa score, management and outcomes of sepsis in southeast asia: a multinational multicenter prospective observational study. j intensive care. 2018;6:9. 6. health mop. indicator 036: mortality in sepsis patients community –acquired [available from: http://healthkpi.moph.go.th/kpi2/kpi/index2/. 7. rhodes a, evans le, alhazzani w, levy mm, antonelli m, ferrer r, et al. surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. intensive care med. 2017;43(3):304-77. 8. seymour cw, rea td, kahn jm, walkey aj, yealy dm, angus dc. severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome. am j respir crit care med. 2012;186(12):1264-71. 9. studnek jr, artho mr, garner jr cl, jones ae. the impact of emergency medical services on the ed care of severe sepsis. am j emerg med. 2012;30(1):51-6. 10. borrelli g, koch e, sterk e, lovett s, rech ma. early recognition of sepsis through emergency medical services prehospital screening. am j emerg med. 2019;37(8):1428-32. 11. andersson h, axelsson c, larsson a, bremer a, gellerstedt m, bång a, et al. the early chain of care in bacteraemia patients: early suspicion, treatment and survival in prehospital emergency care. am j emerg med. 2018;36(12):2211-8. 12. silva e, duarte v, soares m, melo a, calife e, rebouças g, et al. survival analysis of patients with sepsis in brazil. rev soc bras med trop. 2019;52:e20180121. 13. lane dj, wunsch h, saskin r, cheskes s, lin s, morrison lj, et al. epidemiology and patient predictors of infection this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 8 and sepsis in the prehospital setting. intensive care med. 2020;46(7):1394-403. 14. huabbangyang t, sangketchon c, piewthamai k, saengmanee k, ruangchai k, bunkhamsaen n, et al. perception and satisfaction of patients’ relatives regarding emergency medical service response times: a crosssectional study. open access emerg med. 2022;14:15563. 15. huabbangyang t, sangketchon c, ittiphisit s, uoun k, saumok c. predictive factors of outcome in cases of out-of-hospital cardiac arrest due to traffic accident injuries in thailand; a national database study. arch acad emerg med. 2022;10(1):e64. 16. dankert a, kraxner j, breitfeld p, bopp c, issleib m, doehn c, et al. is prehospital assessment of qsofa parameters associated with earlier targeted sepsis therapy? a retrospective cohort study. j clin med. 2022;11(12):3501. 17. singer m, deutschman cs, seymour cw, shankar-hari m, annane d, bauer m, et al. the third international consensus definitions for sepsis and septic shock (sepsis-3). jama. 2016;315(8):801-10. 18. van der wekken l, alam n, holleman f, van exter p, kramer m, nanayakkara p. epidemiology of sepsis and its recognition by emergency medical services personnel in the netherlands. prehosp emerg care. 2015;20(1):90-6. 19. gorordo-delsol la, merinos-sánchez g, estradaescobar ra, medveczky-ordoñez ni, amezcua-gutiérrez ma, morales-segura ma, et al. sepsis and septic shock in emergency departments of mexico: a multicenter point prevalence study. gac med mex. 2020;156(6):486-92. 20. smyth ma, brace-mcdonnell sj, perkins gd. identification of adults with sepsis in the prehospital environment: a systematic review. bmj open. 2016;6(8):e011218. 21. loza-gomez a, hofmann e, noklam c, menchine m. severe sepsis and septic shock in patients transported by prehospital services versus walk in patients to the emergency department. am j emerg med. 2021;45:173-8. 22. kumar s, jangpangi g, bhalla a, sharma n. role of central venous oxygen saturation in prognostication of patients with severe sepsis and septic shock in emergency medical services. int j crit illn inj sci. 2019;9(4):164. 23. gheorghita m, wikner m, cawthorn a, oyelade t, nemeth k, rockenschaub p, et al. reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis. physiol rep. 2022;10(24):e15546. 24. evans l, rhodes a, alhazzani w, antonelli m, coopersmith cm, french c, et al. surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. intensive care med. 2021;47(11):1181247. 25. chen s-h, wang y-c, chao a, liu c-m, chiu c-t, wang m-j, et al. early prediction of survival at different time intervals in sepsis patients: a visualized prediction model with nomogram and observation study. tzu chi med j. 2021;34(1):55-61. 26. brink a, alsma j, verdonschot rjcg, rood ppm, zietse r, lingsma hf, et al. predicting mortality in patients with suspected sepsis at the emergency department; a retrospective cohort study comparing qsofa, sirs and national early warning score. plos one. 2019;14(1):e0211133. 27. nupaw j, surasit k, samuthtai w. evaluation of a nakornping early warning scores (news) at emergency department to predict 24 hours mortality of sepsis patients. j nakornping hosp. 2020;11(1):28-44. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion study limitations conclusion declarations references emergency. 2016; 4 (4): 211-213 photo quiz a 48-year-old man with epigastric pain and melena narvir singh chauhan1∗ 1. department of radiology, dr. rajendra prasad government medical college, tanda kangra, himachal pradesh, india. received: february 2016; accepted: july 2016 cite this article as: a 48-year-old man with epigastric pain and melena. emergency. 2016; 4(4):211-213. figure 1: abdominal plain x ray (a), axial plain abdominal ct scan (b), sagittal multiplanar reconstruction ct scan (c), and axial ct angiography (d). 1. case presentation a 48-year-old male patient was presented to the emergency department with complaint of epigastric pain and melena that had started 3 days ago. the pain had started suddenly and progressed and after a while, he had passed melena stool. he also mentioned some episodes of vomiting that was not bloody. the pain score was about 8/10 (based on verbal quantitative scale) and slightly radiated to his back. he lost his appetite and the pain aggravated by meal. he did not use any drug regularly and had no positive medical history of any specific disease or prior hospital admission. the patient was slightly pale and sweaty. his pulse rate was 80/minute and blood pressure was elevated to 180/100 ∗corresponding author: narvir singh chauhan; department of radiology, dr. rajendra prasad government medical college, tanda kangra, himachal pradesh, india. tel: 9418476622 / fax: 01892267115; email: narvirschauhan@yahoo.com . mmhg. routine blood tests such as liver enzyme and serum amylase levels were normal. complete blood cell count showed mild anemia (haemoglobin =10 g/dl) and leucocytosis (16600/mm3). on physical examination, there were not any positive findings except mild epigastric tenderness without rebound or guarding. electrocardiography revealed normal sinus rhythm without any pathologic findings. the patient was admitted to surgical ward and plain abdominal computed tomography (ct) scan and abdominal ct angiogram was done. the findings of ct are shown in figures 1a-d. what is your diagnosis? . 2. diagnosis ct angiography revealed a dissection in the superior mesenteric artery (sma) starting approximately 7 cm from its origin from aortic orifice. it was distal to the origin of pancreaticoduodenal, middle and right colic branches of sma. the flap measured approximately 3.0 cm in length and one of the jejunal branches of sma was seen to originate from the false lumen. the segments of jejunal loops supplied by this branch showed evidence of pneumatosis suggestive of transmural infarction (figures 2). 3. case fate the patient underwent emergent surgery with resection of the ischemic gut and repair of the dissection. the recovery was uneventful and he was discharged after 3 weeks. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. singh chauhan 212 figure 2: abdominal plain x ray (a), axial plain abdominal ct scan (b), sagittal multiplanar reconstruction ct scan (c), and axial ct angiography (d). location of dissection and intramural air (pneumatosis intestinalis) have been shown with arrows. 4. discussion dissection of visceral artery (idva) is an uncommon event and sma is the commonest site followed by celiac artery (ca) (1, 2). most cases of idva are conservatively managed due to absence of gut ischemia (2, 3). cases of isolated sma dissection resulting in mesenteric ischemia are exceedingly rare and can be potentially fatal. uncontrolled hypertension, arteriosclerosis, cystic medial necrosis, fibromuscular dysplasia, marfans syndrome, ehler-danlos syndrome, trauma and pregnancy have been implicated as possible risk factors in this disease (2, 4). the dissection occurs 3-4 cm distal to its origin from aorta presumably due to large shear stress at this site (5, 6). most of the patients present with acute epigastric pain, nausea, vomiting or melena (4). a vascular murmur may sometimes be heard (5). however, a significant number of patients may remain asymptomatic and the condition may be detected incidentally on cross-sectional imaging (7). contrast enhanced ct (preferably ct angiography) shows the intimal flap or mural thrombus within the true/false lumen. in case of bowel ischemia, associated findings of ischemia such as lack of bowel wall enhancement, intramural air, mesenteric or portovenous air may additionally be present, as seen in our case. ischemia is reported to occur due to occlusion of false lumen and it is estimated that invasive treatment is required in 8.6-34.8% cases of sma dissection due to bowel ischemia and aneurysm enlargement (5). emergency laparotomy with operative repair of dissection is indicated in such cases (5, 8). many surgical procedures have been described for sma dissection including intemectomy, right gastroepiploic artery bypass, graft interposition, arteriotomy with thrombectomy, reimplantation of sma on aorta, fixation of media-intima, and aneurysmorrhaphy (9). the surgical approach has good short term results but its long term outcomes are not yet known (8). endovascular treatment options include thrombolysis, thrombus suction, balloon dilation, stent graft placement and stenting. it is indicated in asymptomatic cases with evidence of progress of dissection or aneurysmal dilatation on surveillance imaging or as first line treatment option in symptomatic and inoperable cases (7, 8). limitations of this approach include risk of re-occlusion, obstruction of side branches in the stented portion, rupture or stent migration (8). conservative approach has been advocated in asymptomatic cases in which ct doesn’t show signs of ischemia and aneurysmal enlargement (8). the therapy includes drug administration for anticoagulation, antiplatelets, blood pressure and pain control. the use of anti-coagulation is suggested when there is clot confinement or constriction of true lumen. these subset of patients require close follow up as treatment failure may occur (8, 9). it is clear that each management option has its own advantages and disadvantages and the optimal treatment varies from patient to patient depending on the symptoms, gut viability, associated co-morbidities, and age. as our patient had clear cut features of gut ischemia on ct angiography, he underwent a potentially lifesaving emergent surgery with resection of the gangrenous small gut loops and repair of dissection. this case highlights the pivotal importance of ct in diagnosis of sma dissection and detection of bowel ischemia. an early and accurate diagnosis is crucial in this subset of cases for selection of optimal treatment protocol as timely surgical intervention in patients with bowel gangrene may be lifesaving. 5. appendix 5.1. acknowledgements none declared. 5.2. conflict of interest none declared. 5.3. funding and support none declared. 5.4. authors’ contributions the authors meet the four criteria for authorship based on the icmje recommendations of medical journal editors. references 1. aydin s, ergun e, fatihoglu e, durhan g, kosar pn. spontaneous isolated celiac artery and superior mesenteric artery dissections: a rare case. polish journal of radiology. 2015;80:470. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 213 emergency. 2016; 4 (4): 213-213 2. tokue h, tsushima y, endo k. imaging findings and management of isolated dissection of the visceral arteries. japanese journal of radiology. 2009;27(10):430-7. 3. verde f, bleich kb, oshmyansky a, black jh, fishman ek, johnson pt. isolated celiac and superior mesenteric artery dissection identified with mdct: imaging findings and clinical course. journal of computer assisted tomography. 2012;36(5):539-45. 4. katsura m, mototake h, takara h, matsushima k. management of spontaneous isolated dissection of the superior mesenteric artery: case report and literature review. world j emerg surg. 2011;6:16. 5. satokawa h, takase s, seto y, yokoyama h, gotoh m, kogure m, et al. management strategy of isolated spontaneous dissection of the superior mesenteric artery. annals of vascular diseases. 2014;7(3):232. 6. mousa ay, coyle bw, affuso j, haser pb, vogel tr, graham am. nonoperative management of isolated celiac and superior mesenteric artery dissection: case report and review of the literature. vascular. 2009;17(6):359-64. 7. gobble rm, brill er, rockman cb, hecht em, lamparello pj, jacobowitz gr, et al. endovascular treatment of spontaneous dissections of the superior mesenteric artery. journal of vascular surgery. 2009;50(6):1326-32. 8. takahashi b, nakayama y, shiroma s, ido k. three case report of spontaneous isolated dissection of the superior mesenteric artery-with an algorithm proposed for the management. annals of vascular diseases. 2015;8(2):120. 9. lv p-h, zhang x-c, wang l-f, chen z-l, shi hb. management of isolated superior mesenteric artery dissection. world journal of gastroenterology: wjg. 2014;20(45):17179. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com case presentation diagnosis case fate discussion appendix references archives of academic emergency medicine. 2023; 11(1): e21 or i g i n a l re s e a rc h effect of out-of-hour admission on fluid treatment of emergency department patients with suspected infection; a multicenter post-hoc analysis marie kristine jessen1,2,3∗, anna drescher petersen1, hans kirkegaard1,2 1. research center for emergency medicine, department of clinical medicine, aarhus university and aarhus university hospital, aarhus, denmark. 2. department of emergency medicine, aarhus university hospital, aarhus, denmark. 3. department of anesthesiology and intensive care, aarhus university hospital, aarhus, denmark. received: october 2022; accepted: december 2022; published online: 31 january 2023 abstract: introduction: sepsis is a life-threatening and common cause of emergency department (ed) referrals. out-of-hour staffing is limited in ed, which may potentially affect fluid administration. this study aimed to investigate fluid volume variation in out-of-hour vs. routine-hour admissions. methods: the present study is a post-hoc analysis of a multicentre, prospective, observational study investigating fluid administration in ed patients with suspected infection, from jan 20th march 2nd, 2020. patient groups were “routine-hours” (rh): weekdays 07:00-18:59 or “out-of-hours” (ooh): weekdays 19:00-06:59 or friday 19:00-monday 06:59. primary outcome was 24-hour total fluid volumes (oral + intravenous (iv )). secondary outcomes were total fluids 0-6 hours, oral fluids 0-6 and 0-24 hours, and iv fluids 0-6 and 0-24 hours. linear regression adjusted for site and illness severity was used. results: 734 patients had suspected infection; 449 were admitted during rh and 287 during ooh. mean (95% ci) total 24-hour fluid volumes were equal in simple infection and sepsis regardless of admission time: simple infection rh: 3640 (3410 3871) ml and ooh: 3681 (3451 3913) ml. sepsis rh: 3671 (3443;3898) ml and ooh: 3896 (3542;4250) ml. oral fluids 0-6h were reduced in simple infection and sepsis among ooh vs. rh. sepsis patients received more 0-6-hour iv fluid when admitted ooh vs. rh. there were no associations between admission time and 0-24-hour oral or iv volumes in simple infection or sepsis. conclusion: admission time did not have an association with 24-hour total fluid volumes. sepsis patients admitted during ooh received more 0-6-hour iv fluids than rh patients, and simple infection and sepsis patients received less oral fluid in 0-6 hours if admitted during ooh vs. rh. keywords:emergency service, hospital; fluid therapy; sepsis; infections; time factors; periodicity cite this article as: kristine jessen m, drescher petersen a, kirkegaard h. effect of out-of-hour admission on fluid treatment of emergency department patients with suspected infection; a multicenter post-hoc analysis. arch acad emerg med. 2023; 11(1): e21. https://doi.org/10.22037/aaem.v11i1.1839. 1. introduction suspected infection and sepsis are very common in emergency department (ed) patients (1-3). despite the overall decrease in sepsis-related mortality rates along with implementation of guidelines (4-7), rates of deterioration, morbidity and mortality remain significant (8-12). early targeted treatment to reduce mortality and morbidity, including in∗corresponding author: marie kristine jessen; research center for emergency medicine, department of clinical medicine, aarhus university and aarhus university hospital, palle juul-jensens boulevard 99, j103, dk-8200 aarhus n, denmark. telephone: 0045-25333286, email: marie.jessen@rm.dk, orcid: https://orcid.org/0000-0001-9445-7690. travenous (iv ) fluid resuscitation, is important (13). for patients with sepsis-induced hypoperfusion, the surviving sepsis campaign (ssc) guideline recommends giving at least 30 ml/kg of iv crystalloid fluid within the first 3 hours. ssc does not give any recommendations on fluid administration in sepsis patients without hypotension or shock. fluid treatment in sepsis patients not in shock is guided only by weak recommendations and fluid administration practice varies (13-16). caring for sepsis patients – including administration of iv fluids – is time-consuming and requires close monitoring of disease progression, which might sometimes be challenging in an ed setting. the organisation and staffing in the ed setting often changes according to time of day and between weekdays and weekthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. kristine jessen et al. 2 ends (17). the out-of-hour (ooh) patient intake and referrals (i.e., ooh primary care) affects the admitted population with increased illness severity, other chief complaints and presentations, etc. (18-20). extensive research has stated a weekend effect, for example, an increased mortality among patients admitted to hospitals in general and in the eds during weekends (21-26). also, ooh (sometimes also called “after-hour”) admission on weekdays (during evening and night-time) is associated with higher mortality (19, 26). for sepsis patients, the weekend effect and ooh admission seem to affect outcomes such as risk of icu admission, risk of intubation, and mortality (26-29). the underlying causes of these effects and the ooh phenomenon have never been clearly established, although both severity of illness and staffing levels have been suggested to be causal in ed studies (19, 20). whether associations exist between fluid administration practice and patient admission time is unknown. we hypothesized, that patients admitted during “routine-hours” received more total fluid than patients admitted during “outof-hours”. if such differences exist, it may be important knowledge to potentially change or uniform practice. this study aimed to assess the effect of varying admission times on fluid administration practice, volume, and iv versus oral administration in ed patients with simple infection and sepsis in the first 6 and 24 hours following admission. 2. methods 2.1. study design and settings this was a post-hoc analysis of a prospective, observational, multicentre study consecutively enrolling patients with suspected infection admitted to any of three eds in central denmark region: regional hospital herning, region hospital randers, and aarhus university hospital from january 20th, 2020, to march 2nd, 2020 (2). the three eds serve a mixed rural–urban population of 0.9 million people and provide 24-hour emergency care to all adult acute patients, except those transferred directly to catheterization laboratories, and stroke units, and women in labor. ed patients are either referred by a general practitioner or brought in by ambulance after an emergency call. in the three eds, patient contacts vary between 15,000 and 63,000 per year. emergency health care in denmark is publicly funded. the original study aimed at describing current 24-hour fluid administration to all ed patients admitted with suspected infection of any severity. the study was approved by the danish patient safety authority (case no.: 31-1521188). approval from an ethics committee was not required according to danish law. 2.2. participants all ed patients at the three sites were screened for eligibility during the study period. we consecutively included all patients who fulfilled all of the following inclusion criteria: age ≥ 18 years, admitted through the ed with suspected infection defined as drawing of a blood culture and/or administration of iv antibiotics within 6 hours of arrival (2). we only included danish citizens with a personal identificationnumber to be able to track them in the electronic patient record. only patients who first presented within the study period and fulfilled all the inclusion criteria were included. we only included patients who were admitted for the entire 24-hour time-period with fluid administration registered. we excluded 1) patients who were admitted due to trauma, 2) patients with serious bleeding defined by the use of more than two units of red blood cells or the need for an invasive intervention for bleeding, and 3) patients, who only received prophylactic antibiotics (e.g., patients scheduled for surgery) who did not have a blood culture drawn. all intravenous fluids ≥ 50 ml were registered. 2.3. fluid registration all included patients had oral and iv fluids registered on a paper case report form (crf) (see original article(2) for the first 24 hours of their hospital stay; including fluids administered in the prehospital setting. all intravenous fluids ≥ 50 ml were registered. intravenous fluids included crystalloids, glucose, albumin, parenteral nutrition, and blood products. oral fluids were registered by the treating nurses and/or by the patient if deemed fully conscious and cooperative. tube feeding was registered as part of oral fluids. for all fluids – oral and intravenous the administration start time was noted. the crf followed the patient for 24 hours or until discharge within 24 hours. in the analyses, we only included patients who were admitted for the entire 24-hour time-period with fluid administration registered. patients were divided into groups of illness severity within 6 hours of ed arrival: simple infection (sequential organ failure assessment (sofa)-score < 2), sepsis (increase in sofascore ≥ 2 from baseline), and septic shock (mean arterial pressure (map) of 65mmhg or greater and serum lactate level > 2 mmol/l (>18mg/dl)) based on the sepsis-3 guidelines using sofa-score (30). descriptive data on vital signs, organ dysfunction, receipt and timing of intravenous antibiotics, comorbidities, mortality, ed length of stay, and in-hospital length of stay were automatically retrieved from the electronic patient record at each hospital. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e21 2.4. outcomes the main outcome of both the original and this post-hoc analysis was the total volume of oral and intravenous (combined) fluids administered within the first 24 hours of admission stratified by illness severity (simple infection or sepsis) and admission time. we also report administered fluid in the following categories: total fluid 0-6 hours, oral fluids 0-6 and 0-24 hours, and iv fluids 0-6 and 0-24 hours, stratified by illness severity (simple infection or sepsis). 2.5. statistical analyses this post-hoc analysis investigated the effect of out-of-hour admission vs. routine-hour-admission on fluid treatment in patients with suspected infection. all inclusion and exclusion criteria were the same as for the original study. for this sub-study, we only included patients with simple infection or sepsis (i.e. a sofa-score ≥ 2 (31)), and excluded patients with septic shock (need for vasopressor to maintain map > 65 mmhg and lactate > 2 mmol/l), since this group only included eight patients. the admission time was registered by a secretary at the time of patients’ presentation to the ed. we subsequently divided patients into two groups according to the admission time: “routine-hours” and “out-of-hours”. “routine-hours” was considered weekdays working hours and defined as monday to friday 07:00-18:59. “out-of-hours” included both weekday nights defined as monday to friday 19:00-06:59 and weekends from friday 19:00 to monday 06:59. the intervals were chosen according to staffing levels; “routine hours” reflected hours with higher staffing levels and “out-of-hours” reflected hours with lower staffing levels in the eds. for the original study, we did not calculate a formal sample size a priori, but based on unpublished data from aarhus university hospital, we anticipated that approximately 1600 patients with suspected infection would present at the three sites within the study period. this anticipated sample size was deemed adequate for the descriptive goal of the original study and for this post-hoc analysis. categorical data are reported as counts and proportions (%) and continuous data as means with standard deviations or medians with interquartile range (iqr, first and third quartile), as appropriate. distributions were assessed for normality using visual inspection of histograms. to assess the association between patient and disease characteristics and fluid administration, we used linear regression models with the amount of fluid within the first 24 hours as the primary outcome; these analyses were adjusted for site and sofa-score (31) and reported with 95% confidence intervals (ci). the decision to adjust for sofascore was based on the assumption that the illness severity of patients admitted during routine-hours and out-of-hours would vary. for all analyses on fluid volumes and differences in these, we included all patients with simple infection or sepsis (n= 726). there was no missing data on neither exposure (admission time), primary or secondary outcomes, nor the adjusting variable for any patients. data was analyzed using stata version 17 (statacorp lp, college station, tx, usa). p < 0.05 was considered as level of significance. 3. results 3.1. characteristics of the study population of all ed patients (9,992 unique patients during the inclusion period at all three sites), 1924 patients fulfilled all inclusion criteria. 24-hour fluid administration was available for 734 (38%) patients. we excluded the eight septic shock patients from further analyses. finally, 726 patients with simple infection or sepsis, a minimum of 24-hour hospital admission, and 24-hour fluids available were included in this study. of these, 443 (61%) were admitted during “routine-hours” and 283 (39%) were admitted during “out-of-hours” (figure 1). baseline characteristics of the included population (n=726) are shown in table 1 based on the admission time. there were no differences in baseline characteristics between patients admitted during “routine-hours” and “out-of-hours”. c-reactive protein (crp) levels were lower in patients admitted during afterhours. 3.2. primary outcome 24-hour total oral and intravenous fluid administration the mean total, combined, oral and intravenous fluid volume administered during the first 24 hours of admission to patients admitted with simple infection during “routine-hours” was 3640 (95% ci: 3410 3871) ml and it was 3681 (95% ci: 3451 3913) ml for patients admitted during “out-of-hours”, with an adjusted mean difference (for site and sofa-score) of 50 (95% ci: -29 398) ml. for patients with sepsis admitted during “routine-hours”, the total volume was 3671 (95% ci: 3443 3898) ml and for sepsis patients admitted during “out-ofhours” 3896 (95% ci: 3542 4250) ml with an adjusted mean difference of 226 (95% ci: -165 616) ml (table 2). 3.3. secondary outcomes 6-hour total oral and intravenous fluid administration total fluid administration of oral and intravenous fluids combined administered during the first 0-6 hours were not statistically significant different between “routine-hours” and “out-of-hours” for patients with simple infection or sepsis patients, with adjusted mean differences of -49 (95% ci: -238 139) and 130 (95% ci: -83 343), respectively (table 2). 3.4. oral and intravenous fluids we found a difference in oral fluid administration during the first 6 hours of admission. patients with simple infection rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. kristine jessen et al. 4 table 1: baseline characteristics of study participants variables simple infection (n=387) p sepsis (n=339) p rh (n=241) oh (n=146) rh (n=202) oh (n=137) age (years) median (iqr) 73 (56 82) 69 (55 81) 0.29 73 (65 83) 73 (68 83) 0.71 gender male, n (%) 113 (47%) 73 (50%) 0.55 116 (57%) 80 (58%) 0.86 anthropometrics height (cm) 170 (163 -177) 171 (164 -179) 0.15 172 (165 -177) 172 (165 -178) 0.91 weight (kg) 74 (62 -87) 76 (64 -88) 0.66 76 (63 -87) 75 (61 -90) 0.77 bmi (kg/m2) 25 (22 -29) 25 (22 -29) 0.98 25 (23 -28) 25 (21 -30) 0.50 do-not-resuscitate/do-not-intubate-orders number (%) 29 (12) 18 (12) 0.93 47 (23) 38 (28) 0.35 vital signs# respiratory rate (/min) 20 (18 -24) 20 (18 -24) 0.93 22 (20 -26) 24 (20 -28) 0.16 saturation (%) 96 (94 -97) 95 (94 -97) 0.23 92 (88 -94) 93 (90 -95) 0.001 heart rate (/min) 92 (80 -103) 94 (85 -110) 0.03 98 (85 -115) 98 (85 -115) 0.93 sbp (mmhg) 130 (113 -144) 136 (118 -148) 0.05 120 (103 -135) 119 (99 -133) 0.47 map (mmhg) 91 (81 -101) 94 (84 -104) 0.05 85 (73 -98) 84 (72 -95) 0.41 temperature (◦c) 38.0(37.5 -38.4) 38.3(37.7 -39.0) 0.04 38.1(37.4 -38.8) 38.4(37.6 -39.1) 0.15 gcs 15 (15 -15) 15 (15 -15) 0.90 15 (15 -15) 15 (13 -15) 0.03 sofa-score total 0 (0 -1) 0 (0 -1) 0.36 2 (2 -4) 3 (2 -4) 0.27 respiration 0 (0 -0) 0 (0 -0) 2 (0 -2) 2 (0 -2) coagulation 0 (0 -0) 0 (0 -0) 0 (0 -0) 0 (0 -0) liver 0 (0 -0) 0 (0 -0) 0 (0 -1) 0 (0 -0) cardiovascular 0 (0 -0) 0 (0 -0) 0 (0 -0) 0 (0 -0) central nervous system 0 (0 -0) 0 (0 -0) 0 (0 -0) 0 (0 -1) renal 0 (0 -0) 0 (0 -0) 0 (0 -1) 0 (0 -0) laboratory findings creatinine (µmol/l) 72 (57 -95) 71 (57 -91) 0.64 85 (62 -123) 88 (64 -126) 0.98 platelets (× 109/l) 267 (215 -37) 253 (193 -16) 0.07 218 (174 -70) 220 (154 -03) 0.72 bilirubin (µmol/l) 9 (7 -14) 9 (7 -14) 0.93 12 (8 -23) 11 (7 -20) 0.46 leukocytes (× 109 /l) 11.3 (8.6 -4.7) 11.0 (8.4 -4.6) 0.59 11.7 (8.6 -5.7) 12.1 (8.6 -7.4) 0.53 crp (mg/l) 112 (42 -194) 61 (23 -150) 0.002 79 (23 -203) 68 (25 -127) 0.33 lactate (mmol/l) 1.4 (0.9 -1.9) 1.6 (0.8 -2.9) 0.54 1.6 (1.1 -2.5) 1.5 (1.0 -2.4) 0.53 time to blood culture (hours) 0.6 (0.4 -0.8) 0.5 (0.3 -0.7) 0.06 0.5 (0.2 -0.7) 0.5 (0.3 -0.8) 0.75 antibiotics (hours) 2.3 (1.1 -4.7) 1.8 (0.7 -3.4) 0.15 1.5 (0.4 -3.3) 1.6 (0.8 -2.9) 0.88 infectious source* respiratory 66 (27) 34 (23) 91 (46) 50 (37) urinary 55 (23) 26 (18) 26 (13) 28 (20) skin/soft tissue 34 (14) 14 (10) 11 (5) 3 (2) abdominal 34 (14) 28 (19) 20 (10) 20 (15) bacteriaemia 1 (0.4) -** -** 1 (1) viral 5 (2) 11 (8) 6 (3) 7 (5) other 9 (4) 9 (6) 7 (3) 4 (3) unknown 14 (6) 13 (9) 23 (11) 9 (7) length of stay ed (hours) 11.5 (6.7 -5.0) 15.6 (7.4 -5.5) 0.47 10.3 (6.0 -5.6) 16.0 (6.7 -1.8) 0.06 in-hospital (hours) 78 (49 -147) 96 (56 -157) 0.53 131 (71 -190) 120 (75 -181) 0.52 mortality in-hospital 5 (2) 4 (3) 0.67 14 (7) 7 (5) 0.50 90-day 23 (10) 17 (12) 0.65 42 (21) 27 (20) 0.81 all data are presented as medians with (interquartile range; iqr) or frequency (%). bmi: body mass index; ed: emergency department; gcs: glasgow coma scale; map: mean arterial pressure; sbp: systolic blood pressure; sofa score: sequential organ failure assessment score (30); crp: c-reactive protein; rh: routine-hour admission; oh: out-of-hour admission. p-values are based on wilcoxon rank-sum test and pearson’s x2 . *numbers do not sum up to 100%, since it was possible to have more than one infectious source. therefore, it was not possible to add p-values. **represents no patients in this category # worst within 6h. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e21 table 2: comparing the received fluid volumes between patients admitted to emergency department during the routine hours and out-ofhours variables fluid volumes (ml) mean difference (95% ci) p value total sofa adjusted simple infection oral fluids 0-6 hours routine-hours 653 (584 721) 0.036 out-of-hours 526 (442 – 611) -126 (-235 -17) -117 (-227 -8) oral fluids 0-24 hours routine-hours 1897 (1763 – 2031) 0.27 out-of-hours 1758 (1597 – 1919) -139 (-351 – 73) -117 (-329 – 95) iv fluids 0-6 hours routine-hours 925 (819 – 1032) 0.44 out-of-hours 1006 (874 – 1138) 80 (-90 – 251) 67 (-104 – 239) iv fluids 0-24 hours routine-hours 1744 (1529 – 1958) 0.30 out-of-hours 1923 (1716 – 2132) 180 (-139 – 499) 167 (-152 – 487) oral and iv fluids 0-6 hours routine-hours 1577 (1460 – 1695) 0.60 out-of-hours 1532 (1388 – 1675) 46 (233 – 142) -49 (-238 – 139) oral and iv fluids 0-24 hours routine-hours 3640 (3410 – 3871) 0.78 out-of-hours 3681 (3451 – 3913) -41 (305 – 387) 50 (-298 – 398) sepsis oral fluids 0-6 hours routine-hours 428 (370 – 487) 0.002 out-of-hours 285 (223 – 346) -144 (-231 -56) -139 (-225 -54) oral fluids 0-24 hours routine-hours 1366 (1247 1485) 0.23 out-of-hours 1248 (1098 1398) -118 (-307 72) -113 (-299 73) iv fluids 0-6 hours routine-hours 1207 (1077 1337) 0.009 out-of-hours 1468 (1290 1647) 261 (46 477) 270 (68 471) iv fluids 0-24 hours routine-hours 2305 (2079 2531) 0.067 out-of-hours 2648 (2312 2983) 343 (-45 731) 338 (-23 701) oral and iv fluids 0-6 hours routine-hours 1636 (1505 1766) 0.23 out-of-hours 1754 (1565 1942) -118 (-103 338) -130 (-83 343) oral and iv fluids 0-24 hours routine-hours 3671 (3443 3898) 0.26 out-of-hours 3896 (3542 4250) 225 (175 626) 226 (-165 616) data are presented with 95% confidence interval (ci). p-value for the adjusted analyses are reported. iv: intravenous; sofa: sequential organ failure assessment. ceived a mean of 653 (95%ci: 584 721) ml in the first 6 hours of admission if admitted during “routine-hours”, whereas patients with simple infection admitted during “out-of-hours” received a mean of 526 (95%ci: 442 611) ml, (adjusted mean difference: -117 (95% ci: -227 -8)) ml. a similar difference was seen in patients with sepsis. for patients with sepsis admitted during “routine-hours” the mean oral fluid in the first 6 hours was 428 (95%ci: 370 487) ml and for “out-of-hours” 285 (95%ci: 223 346) ml, (adjusted mean difference: -139 (95% ci: -225 -54)) (table 2). looking at 0-24 hours, the variation in oral fluid treatment associated with admission time was no longer present (table 2). for iv fluids administered in the initial 6 hours of admission, we found that iv fluid volumes were the same for patients with simple infection admitted during “routine-hours” and “out-of-hours”: 925 (95%ci: 819 1032) ml for “routinehours” and 1006 (95% ci: 874 1138) ml for “out-of-hours”, (adjusted mean difference: 67 (95% ci: 67 (-104 239)). patients with sepsis admitted during “routine-hours” had significantly less iv fluids administered in the first six hours compared to patients admitted during “out-of-hours”. they received a mean of 1207 (95% ci: 1077 1337) ml if admitthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. kristine jessen et al. 6 figure 1: patient selection flow chart. * septic shock patients were not included in analyses since only 8 patients had septic shock. ted during “routine-hours” and 1468 (95% ci: 1290 1647) ml if admitted during “out-of-hours” (adjusted mean difference: 270 (95% ci: 68 471)). as with oral fluid treatment, the variation found in iv fluid treatment of sepsis patients was limited to the first 6 hours and no differences were found in 24-hour iv fluid volumes according to admission time in simple infection or sepsis (table 2). 4. discussion we found no association between total fluid administration practice and time of admission, neither looking at the first 0-6 hours or 0-24 hours of admission regardless of severity of illness. however, we found that patients with simple infection and sepsis both received less oral fluid and patients with sepsis received more intravenous fluids during the first 6 hours, when admitted during “out-of-hours” compared to “routinehours”. these differences, however, were not present after 24 hours. since we hypothesized that patients admitted during “routine-hours” received more total fluid than patients admitted during “out-of-hours”, for example due to lower staffing levels during out-of-hours, it was rather surprising that total fluid volumes were the same: total fluid administration practise does not appear to be affected by organisational changes or staffing in the ed depending on day of week and time of day in the three danish eds. a korean study of ed patients with septic shock, found an even higher sepsis bundle compliance and adherence to fluid resuscitation recommendations for patients admitted during this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e21 the night (32), whereas a brazilian study found lower total bundle adherence, but the same adherence to fluid resuscitation goals in night versus day admissions (33). an australian study found no association between admission time and receiving fluids at all or time to fluid administration (34). the increased attention towards sepsis patients and the necessity of early therapy and delivering (time-consuming) care to improve clinical outcome for these patients in recent years may have contributed to the uniformity of the total fluid treatment regardless of time of admission, which we found. the surviving sepsis campaign guideline recommends giving at least 30 ml/kg of iv crystalloid fluid to patients with sepsis induced hypoperfusion or shock within the first 3 hours. this does not apply to patients without hypotension or septic shock (35). we found small differences in the preferred administrative route used in the initial 6 hours and found, that sepsis patients admitted during “out-of-hours” received significantly more intravenous fluids and less oral fluids, than patients admitted during “routine-hours” with sepsis. this could be explained by an intention to spare time or not to awaken and disturb sleeping patients during late hours/night-time to give oral fluids and instead use intravenous fluid treatment during the initial 6 hours of “out-ofhour” admissions. since intravenous fluids have been suggested to destroy glycocalyx, this strategy may be unfortunate, especially if administered rapidly (15, 36). however, the association was non-existing when exceeding the first 6 hours of admission. due to the organisation of the danish healthcare system, all danish citizens are assigned a general practitioner (gp). in daytime, the gp refers the patient in need of hospital care; yet, in out-of-hours and weekends referrals go through outof-hour gps (who do not know the patient) or emergency service dispatch centres after emergency calls. because of this, we expected patients admitted during “out-of-hours” to have more severe illness than during “routine-hours” and chose to adjust for illness severity in terms of sofa-score in our analyses before conducting our analyses. according to the blood test results, vital signs and illness severity scores, this was not the case. no apparent differences in baseline characteristics were found between patients admitted during “routinehours” and “out-of-hours” except for differences in crp level (table 1). when adjusting for illness severity in our analyses to decrease the impact of potential baseline differences, it did not change the mean fluid administration differences, but there may be unmeasured significant differences in the patient groups that we were not able to describe with the collected data and, therefore, also did not adjust for in our analyses. a substantial part of the study population was excluded from the analyses (figure 1). we especially suspected the group where fluid registration was not possible or available for the full 24 hours (n=214) to have an overrepresentation of patients admitted during “out-of-hours”. one could assume that lower staffing would limit inclusion in a descriptive study of patients fulfilling inclusion criteria, i.e., patients not starting the crf (timely) due to limited staffing. this could affect a considerable part of the non-included patients, who would have been in the “out-of-hour” category. however, the pattern of patient admission during “routine-hour” and “outof-hour” for excluded patients was similar to that of the included patients, described in the results section, eliminating this concern. 5. strengths and limitations this study was a multicentre study, which made it possible to enrol a large proportion of patients during a relatively short period of time, generating a solid basis for comparison. patients had 24-hour fluids registered on a paper crf, so we were also able to include oral fluids, which is a strength. also, we included all eligible patients regardless of do-notresuscitate/-intubate orders or limitations in care. adjusting for illness severity, using sofa-score, as a potential confounder of fluid volumes may not be the most appropriate approach in this less sick population, since it may not cover the entire differences in illness severity in for example patients who will never be invasively ventilated or receive vasopressors, although this approach is suggested in sepsis-3 (30). also, we could have considered adjusting for age, since age could decrease fluid volumes to avoid fluid overload in elderly patients with an increased risk of heart failure. all patients were enrolled during winter season, so no seasonal variations may have influenced the results, however, this limits generalizability to other seasons. of note, the inclusion period ended before the first covid-19 patient in central denmark region was admitted on march 6, 2020. the “time-of-admission” categories were arbitrarily defined but in accordance with staffing at the largest site. other studies have varying definitions of “out-of-hours” (19, 37, 38). in this study, time of admission categories were limited to “routine-hours” and “out-of-hours”, further subdivisions could be of interest, including weekdays vs. weekends. the study only included patients who were admitted for 24 hours or more and for whom fluid registration was available for the full 24 hours. for patients admitted during late “routine-hours” the administered fluid for the first 6 hours was for the most part administered during “out-of-hours” and for patients admitted during late “out-of-hours” the administered fluid during the first 6 hours happened during “routine-hours”, which might level differences between the groups. although this post-hoc analysis investigated patients admitted to three relatively large emergency departments in centhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. kristine jessen et al. 8 tral denmark region, we are not able to conclude anything about generalizability to other countries. however, the care given both during routine-hours and out-of-hours must depend on staffing, triage and prioritization of recourses in general. these factors did not seem to affect total fluid volumes in 24 hours, at least in the three included sites. 6. conclusions no association was found between total fluid administration practice and time of admission in this post-hoc analysis looking at combined oral and intravenous fluid volumes in 0-6 hours or 0-24 hours of admission, regardless of severity of infection. however, we found differences in distributions between oral and intravenous fluids within the first 6 hours of admission; patients with simple infection and sepsis admitted during “routine-hours” received more oral fluids and patients with sepsis received less intravenous fluids than patients admitted during “out-of-hours”. these differences were, however, limited to the initial 6 hours of admission. 7. declarations 7.1. acknowledgments we are very grateful to the clinical staff of doctors and nurses at the participating departments for their important contribution. 7.2. conflict of interest none of the authors have any conflicts of interest in regard to this manuscript 7.3. fundings and supports there was no funding support applicable to this project but the primary project received grants from carl and ellen hertz foundation, frimodt-heineke foundation, ruth & holger hesses memorial fund, aarhus university, “akutpuljen” central denmark region and health research foundation of central denmark region. the funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. 7.4. authors’ contribution 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admission rates and 30-day mortality for 20 common medical conditions. bmj open. 2015;5(3):e006731. 20. duvald i, moellekaer a, boysen ma, vest-hansen b. linking the severity of illness and the weekend effect: a cohort study examining emergency department visits. scand j trauma resusc emerg med. 2018;26(1):72. 21. aylin p, yunus a, bottle a, majeed a, bell d. weekend mortality for emergency admissions. a large, multicentre study. qual saf health care. 2010;19(3):213-7. 22. barba r, losa je, velasco m, guijarro c, garcía de casasola g, zapatero a. mortality among adult patients admitted to the hospital on weekends. eur j intern med. 2006;17(5):322-4. 23. bell cm, redelmeier da. mortality among patients admitted to hospitals on weekends as compared with weekdays. n engl j med. 2001;345(9):663-8. 24. sharp al, choi h, hayward ra. don’t get sick on the weekend: an evaluation of the weekend effect on mortality for patients visiting us eds. am j emerg med. 2013;31(5):835-7. 25. cram p, 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bauer m, et al. the third international consensus definitions for sepsis and septic shock (sepsis-3). jama. 2016;315(8):801-10. 31. seymour cw, liu vx, iwashyna tj, brunkhorst fm, rea td, scherag a, et al. assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). jama. 2016;315(8):762-74. 32. you js, park ys, chung sp, lee hs, jeon s, kim wy, et al. relationship between time of emergency department admission and adherence to the surviving sepsis campaign bundle in patients with septic shock. crit care. 2022;26(1):43. 33. ranzani ot, monteiro mb, besen b, azevedo lcp. association of sepsis diagnosis at daytime and on weekdays with compliance with the 3-hour sepsis treatment bundles. a multicenter cohort study. ann am thorac soc. 2020;17(8):980-7. 34. kabil g, frost sa, mcnally s, hatcher d, saavedra a, suster cje, et al. identifying factors associated with intravenous fluid administration in patients with sepsis presenting to the emergency department: a retrospective this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. kristine jessen et al. 10 cohort study. bmc emerg med. 2022;22(1):98. 35. rhodes a, evans le, alhazzani w, levy mm, antonelli m, ferrer r, et al. surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. crit care med. 2017;45(3):486-552. 36. byrne l, obonyo ng, diab sd, dunster kr, passmore mr, boon ac, et al. unintended consequences: fluid resuscitation worsens shock in an ovine model of endotoxemia. am j respir crit care med. 2018;198(8):1043-54. 37. maggs f, mallet m. mortality in out-of-hours emergency medical admissions–more than just a weekend effect. j r coll physicians edinb. 2010;40(2):115-8. 38. khanna r, wachsberg k, marouni a, feinglass j, williams mv, wayne db. the association between night or weekend admission and hospitalization-relevant patient outcomes. j hosp med. 2011;6(1):10-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion strengths and limitations conclusions declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 140 emergency (2016); 4 (3): 140-144 original article bedside ultrasonography versus brain natriuretic peptide in detecting cardiogenic causes of acute dyspnea keihan golshani, mehrdad esmailian, aniseh valikhany*, majid zamani emergency department, al-zahra hospital, isfahan university of medical sciences, isfahan, iran. *corresponding author: aniseh valikhany; emergency department, al-zahra hospital, soffeh blvd, isfahan, iran. emaildr.valikhany@yahoo.com, tel: 09135342151. received: may 2015; accepted: september 2015 abstract introduction: acute dyspnea is a common cause of hospitalization in emergency departments (ed).distinguishing the cardiac causes of acute dyspnea from pulmonary ones is a major challenge for responsible physicians in eds. this study compares the characteristics of bedside ultrasonography with serum level of blood natriuretic peptide (bnp) in this regard. methods: this diagnostic accuracy study compares bedside ultrasonography with serum bnp levels in differentiating cardiogenic causes of acute respiratory distress. echocardiography was considered as the reference test. a checklist including demographic data (age and sex), vital signs, medical history, underlying diseases, serum level of bnp, as well as findings of chest radiography, chest ultrasonography, and echocardiography was filled for all patients with acute onset of dyspnea. screening characteristics of the two studied methods were calculated and compared using spss software, version 20. results: 48 patients with acute respiratory distress were evaluated (50% female). the mean age of participants was 66.94 ± 16.33 (28-94) years. based on the results of echocardiography and final diagnosis, the cause of dyspnea was cardiogenic in 20 (41.6%) cases. bedside ultrasonography revealed the cardiogenic cause of acute dyspnea in 18 cases (0 false positive) and bnp in 44 cases (24 false positives). the area under the roc curve for bedside ultrasonography and bnp for differentiating the cardiogenic cause of dyspnea were 86.4 (95% ci: 74.6-98.3) and 66.3 (95% ci: 49.8-89.2), respectively (p = 0.0021). conclusion: it seems that bedside ultrasonography could be considered as a helpful and accurate method in differentiating cardiogenic causes of acute dyspnea in emergency settings. nevertheless, more study is needed to make a runaway algorithm to evaluate patients with respiratory distress using bedside ultrasonography, which leads to rapid therapeutic decisions in a short time. keywords: ultrasonography; natriuretic peptide, brain; dyspnea; echocardiography; emergency service, hospital cite this article as: golshani k, esmailian m, valikhany a, zamani m. bedside ultrasonography versus brain natriuretic peptide in detecting cardiogenic causes of acute dyspnea. emergency. 2016; 4(3):140-144. introduction: cute dyspnea is a common cause of hospitalization in emergency departments (ed) (1). there are some clinical and para clinical measures such as patients’ history, physical examination and bedside ultrasonography that help physicians differentiate cardiac causes of acute respiratory distress from pulmonary ones. some have introduced diagnostic rules such as the framingham heart failure criteria. but, due to their low sensitivity and high specificity, they cannot distinguish acute heart failure from non-cardiac causes well (2). on the other hand, the sensitivity of electrocardiography (ecg) and bedside ultrasonography are not high enough to exclude the presence of cardiogenic pulmonary edema, as well (2, 3). conventional echocardiography is an important diagnostic tool for screening and diagnosing heart failure but it is not available 24 hours a day and 7 days a week, additionally it needs many training time for skillful application. brain natriuretic peptide (bnp) or n-terminal of the pro-hormone brain natriuretic peptide (nt-pro-bnp) has been shown to be able to rule out or establish the diagnosis of cardiogenic causes of acute respiratory distress (1). but, some diseases such as renal failure, critical illness, pulmonary heart disease, arrhythmia, anemia, valvular heart diseases and muscular diseases can affect the results of bnp measures (1, 4). nowadays, bedside ultrasonography is integrated into the daily practice of emergency physicians, which helps them ameliorate the accuracy of their diagnoses and managements. pulmonary ultrasonography helps us find a mailto:dr.valikhany@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 141 emergency (2016); 4 (3): 140-144 lung pathologies in a short period of time, by interpreting the artifacts such as comet tails. these artifacts have high sensitivity, but low specificity in diagnosing pulmonary edema (5-7). in this study, we compare bedside ultrasonography with bnp in differentiating cardiogenic causes of acute dyspnea. methods: study design this diagnostic accuracy study compares bedside ultrasonography with serum bnp levels in differentiating cardiogenic cause of acute respiratory distress from pulmonary sources. echocardiography was considered as the reference test. the study was conducted in the emergency department of al-zahra hospital, isfahan, iran, with more than 80000 patients admitted to the ed annually and a 40% admission rate. before the initiation of the study, a 10-day local workshop was taught by a board-certified attending emergency medicine physician and a cardiologist, focusing on bedside ultrasonography with both didactic and hands-on trainings. at the time of admission, we obtained a written informed consent from participants or their legal guardians. the research was approved by institutional review board of ethic committee. participants the study population consisted of those who were admitted to the ed with acute onset of dyspnea between november 2013 and april 2014. intubated and traumatic patients as well as patients with myocardial infraction and history of end stage renal disease were excluded. in addition, cases with the serum creatinine level above the normal range during laboratory evaluation were excluded. a checklist including demographic data (age and sex), vital signs, medical history, underlying diseases, serum level of bnp, as well as findings of chest radiography, chest ultrasonography, and echocardiography was filled for all participants. procedure patients were enrolled with convenience sampling method. on admission, after history taking and physical examination, an echocardiogram and a bedside ultrasonography were performed, and a blood sample was drawn for laboratory examinations (including bnp levels) during the first 15 minutes of admission. for measuring bnp level (by bayer diagnostic advia centaur bnp assay method) 2 ml of peripheral venous blood sample was sent to the laboratory in a vacuum tube containing edta. bedside ultrasonography was done with an (mylab 25 gold 2009) ultrasound machine (biosound esaote, inc., indianapolis, in) using a ca430 curved array (3.5-5 mhz) and a la523 linear array transducer (5.0 to 13.0 mhz) by trained emergency medicine residents within 30 minutes of admission. the majority of patients were in sitting or supine position in accordance with their comfort position. at first, ejection fraction (ef) of heart was estimated visually, via four-chamber, two-chamber, long axis and short axis views of the heart. ef was classified as good in case of ef ≥ 40% and low when ef was less than 40%. for performing ultrasonography, each hemi thorax was divided into 2 anterior (upper and lower) and 2 lateral zones. anterior zone was the area between sternum and anterior axillary line while lateral zone was between anterior and posterior axillary lines. these zones were divided into upper and lower zones by the third intercostal space as a border. lungs were scanned for presence of pleural sliding, b-lines and a-lines. pleural sliding is the back and forth movement of visceral and parietal pleura. b-lines are vertical pleural-based discrete, laser-like, hyper-echoic reverberation artifacts. they move with respiration simultaneously and extend to the bottom of the screen without fading. a -lines are horizontal hyper-echoic reverberation lung artifacts that are separated from each other by an equal distance. for differentiating diastolic heart failure from pulmonary causes of acute respiratory distress, inferior vena cava (ivc) collapsibility index was measured. ivc collapsibility was defined as follows: maximum axial diameter of ivc minus minimum axial diameter of ivc divided by maximum axial diameter of ivc (ivc max ivcmin/ivcmax). ivc diameters were measured at 2-3 centimeters from the right atrium, during expiration (ivcmax) and inspiration (ivcmin) with a curvilinear probe located longitudinally on sub-xyphoid area. diastolic dysfunction was considered as source of acute dyspnea if ef was lower than 40% or ef was more than 40% but ivc collapsibility index was lower than 50%. ultrasonography performance took 6 minutes for each patient. all echocardiography were performed by an expert cardiologist, who was blinded to clinical situation of patients. final diagnosis of patients was decided based on clinical, laboratory, imaging and response to treatment findings by an expert cardiologist together with an internist. statistical analysis total sample size of this study was estimated 48 cases (zα = 95%, p= 50%, d =15%). data analysis was performed using spss software, version 20. quantitative data were reported as frequency and percentage, and qualitative ones as mean and standard deviation. sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) of bedside ultrasonography compared to bnp in differentiating cardiogenic causes of acute dyspnea were calculated. in addition, area under the receiver operating characteristic (roc) curve with 95% confidence interval (ci) was calculated for the two diagnostic tests. chi-square, fisher’s exact test, and t-test were used for comparing the discrete this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com golshani et al 142 and continuous variables. p-value < 0.05 was considered statistically significant. results: 48 patients with acute respiratory distress were evaluated (50% female). the mean age of participants was 66.94 ± 16.33 (28-94) years. table 1 compares baseline characteristics of the studied patients. based on the results of echocardiography and final diagnosis, the cause of dyspnea was cardiogenic in 20 (41.6%) cases. bedside ultrasonography revealed the cardiogenic cause of acute dyspnea in 18 cases (0 false positive) and bnp in 44 cases (24 false positives). table 2 summarizes final diagnosis of patients based on imaging, laboratory, and clinical findings. final diagnosis of patients regarding the source of dyspnea was 100% compatible with echocardiographic results. the area under the roc curve for bedside ultrasonography and bnp for differentiating the cardiogenic cause of dyspnea were 86.4 (95% ci: 74.6-98.3) and 66.3 (95% ci: 49.8-89.2), respectively (figure 1, p = 0.0021). table 3 summarizes the screening performance characteristics of the two studied diagnostic tests. discussion: based on the results of the present study, bedside ultrasonography had better screening performance characteristics compared to bnp in detection of cardiogenic causes of dyspnea. the comparison of area under the roc curve for the two tests showed significant accuracy of bedside ultrasonography in this regard. the causes of acute dyspnea divide into major categories of cardiac and non-cardiac. distinguishing between these two categories is the first step in choosing therapeutic approach and still remains as one of the frequent challenges of emergency physicians. in this regard, some facilities such as bnp measurement and echocardiography can be helpful (8). multiple studies have shown high diagnostic accuracy of serum bnp in ruling out heart failure as a cause of acute dyspnea (9-12). yet, the high rate of cardiac and renal dysfunction in critically ill patients limits the discriminative role of bnp. in the present study, the sensitivity of bnp in 703 pg/ml cut-off was 70% while arques et al. showed 86.4% and 68% sensitivity of bnp in 253 pg/ml and 480 pg/ml cut-offs, respectively (13). serum bnp ≥ 22 pmol/l precisely reflected the final diagnosis of heart failure with 93% sensitivity and 90% specificity in davis et al. study (14). in contrast to several studies in this regard, the accuracy of bnp in the present study was slightly low (15-18). this could be explained by the different cut-offs used for bnp in different studies. the accuracy of bedside ultrasonography in prediction of cardiac origin of dyspnea was known to be high (1). table 1: baseline characteristics of participants based on cause of dyspnea characteristics cause of dyspnea p-value cardiogenic non-cardiogenic age (year) 64.7±21.2 68.1±13.8 0.6 sex male 9 (37.5) 15 (62.5) 0.55 female 11 (45.8) 13 (54.2) history of chf* yes 5 (35.7) 9 (64.3) 0.748 no 15 (45.5) 18 (54.5) coronary artery disease yes 14 (43.8) 18 (56.3) 0.763 no 6 (37.5) 10 (62.5) copd* yes 4 (44.4) 5 (55.6) 1.000 no 16 (41) 23 (59) asthma yes 1 (33.3) 2 (66.7) 1.000 no 19 (42.2) 26 (57.8) hypertension yes 6 (40) 9 (60) 1.000 no 14 (42.4) 19 (57.6) jugular venous distension yes 3 (30) 7 (70) 0.488 no 17 (44.7) 23 (55.3) brain natriuretic peptide (pg/ml) 2819±4095 1433±3029 0.184 ejection fraction (%) 48±12 40±13 0.04 table 2: final diagnosis of patients based on imaging, laboratory, clinical findings, and response to treatment diagnosis number (%) asthma 3 (3.6) pulmonary edema 19 (39.6) pulmonary thromboembolism 10 (20.8) pneumonia 4 (8.3) myocardial infraction 3 (6.3) copd* 5 (10.4) pleural effusion 1 (2.1) emotional 1 (2.1) *copd: chronic obstructive pulmonary disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 143 emergency (2016); 4 (3): 140-144 ultrasonography is more accurate in distinguishing free pleural effusion (19). in the majority of studies, bedside ultrasonography was performed by experienced operators within 10 minutes, and many studies claim completion of the exam within 3-5 minutes (20). in a study by gargani et al. bedside ultrasonography in patients with acute dyspnea significantly correlated with their bnp values (1). ultrasonography was shown to be accurate for differentiating cardiogenic acute dyspnea from those caused by primary pulmonary disease in the emergency setting (21). multiple b-lines have been 100% sensitive and 92% specific in the diagnosis of pulmonary edema (22). in addition, the finding of diffuse multiple b-lines in bedside ultrasonography has had 95% specificity and 97% sensitivity in diagnosis of cardiogenic pulmonary edema (23). if these findings are confirmed in a large number of patients, bedside ultrasonography could become a valuable tool for situations where bnp is not available or in settings where other techniques are not readily available such as remote area, or even in out-of-hospital settings. if we use bnp along with bedside ultrasonography in order to optimize its diagnostic potential, we could reach the final diagnosis in less time. yet, in addition to operator dependency, ultrasonography has some limitations such as application difficulties in obese patients, ribcage, and presence of subcutaneous emphysema (24). conclusion: it seems that bedside ultrasonography could be considered as a helpful and accurate method in differentiating cardiogenic causes of acute dyspnea in emergency settings. nevertheless, more study is needed to make a runaway algorithm to evaluate patients with respiratory distress using bedside ultrasonography, which leads to rapid therapeutic decisions in a short time. acknowledgment: the contributions of all emergency department staffs of alzahra hospital, isfahan, is appreciated. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. gargani l, frassi f, soldati g, tesorio p, gheorghiade m, picano e. ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides. european journal of heart failure. 2008;10(1):70-7. 2. fonseca c, oliveira ag, mota t, et al. evaluation of the performance and concordance of clinical questionnaires for the diagnosis of heart failure in primary care. european journal of heart failure. 2004;6(6):813-20. 3. peacock wf. the evolving role of bnp in the diagnosis and treatment of chf: a summary of the bnp consensus panel report. emergency medicine cardiac research and education group international (1). 2005. 4. copetti r, soldati g, copetti p. chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome. cardiovascular ultrasound. 2008;6(1):16. 5. lichtenstein d, meziere g, biderman p, gepner a, barre o. the comet-tail artifact: an ultrasound sign of alveolar figure 1: the area under the receiver-operating characteristic (roc) curve for bedside ultrasonography and brain natriuretic peptide (bnp) for differentiating the cardiogenic causes of acute dyspnea (p = 0.0021). 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1-specificity bnp roc area: 0.6634 ultrasonography roc area: 0.8643 reference table 3: screening performance characteristics of bedside ultrasonography and brain natriuretic peptide (bnp) characteristics test (95% confidence interval) p-value ultrasonography bnp5 sensitivity 80 (55.7-93.4) 70 (50.5-90.4) 0.0021 specificity 92.8(75-98.7) 75 (54.7-88.5) ppv1 88.9 (63.9-98) 68.1 (45.1-85.2) npv2 86.7 (68.3-95.6) 80.7 (60-92.6) plr3 8 (2.1-29.8) 2.1 (1.09-4.2) nlr4 0.15(0.06-0.36) 0.23 (0.1-0.53) accuracy 87.5 (74.75-95.27) 75 (60.4-86.36) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. 5. bnp’s characteristics were calculated in 703 pg/ml cut-offs. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com golshani et al 144 interstitial syndrome. american journal of respiratory and critical care medicine. 1997;156(5):1640-6. 6. stevenson lw, perloff jk. the limited reliability of physical signs for estimating hemodynamics in chronic heart failure. jama. 1989;261(6):884-8. 7. soldati g, copetti r, sher s. sonographic interstitial syndrome the sound of lung water. journal of ultrasound in medicine. 2009;28(2):163-74. 8. ziskin m, thickman d, goldenberg n, lapayowker m, becker j. the comet tail artifact. journal of ultrasound in medicine. 1982;1(1):1-7. 9. wang cs, fitzgerald jm, schulzer m, mak e, ayas nt. does this dyspneic patient in the emergency department have congestive heart failure? jama. 2005;294(15):1944-56. 10. maisel as, krishnaswamy p, nowak rm, et al. rapid measurement of b-type natriuretic peptide in the emergency diagnosis of heart failure. n engl j med. 2002;347(3):161-7. 11. mccullough pa, nowak rm, mccord j, et al. b-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from breathing not properly (bnp) multinational study. circulation. 2002;106(4):416-22. 12. doust ja, glasziou pp, pietrzak e, dobson aj. a systematic review of the diagnostic accuracy of natriuretic peptides for heart failure. arch intern med. 2004;164(18):1978-84. 13. arques s, roux e, sbragia p, et al. usefulness of bedside tissue doppler echocardiography and b-type natriuretic peptide (bnp) in differentiating congestive heart failure from noncardiac cause of acute dyspnea in elderly patients with a normal left ventricular ejection fraction and permanent, nonvalvular atrial fibrillation: insights from a prospective, monocenter study. echocardiography. 2007;24(5):499-507. 14. davis m, espiner e, yandle t, et al. plasma brain natriuretic peptide in assessment of acute dyspnoea. the lancet. 1994;343(8895):440-4. 15. morrison lk, harrison a, krishnaswamy p, kazanegra r, clopton p, maisel a. utility of a rapid b-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. journal of the american college of cardiology. 2002;39(2):202-9. 16. cabanes l, richaud-thiriez b, fulla y, et al. brain natriuretic peptide blood levels in the differential diagnosis of dyspnea. chest journal. 2001;120(6):2047-50. 17. berdagué p, caffin p-y, barazer i, et al. use of n-terminal prohormone brain natriuretic peptide assay for etiologic diagnosis of acute dyspnea in elderly patients. american heart journal. 2006;151(3):690-8. 18. lainchbury jg, campbell e, frampton cm, yandle tg, nicholls mg, richards am. brain natriuretic peptide and nterminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. journal of the american college of cardiology. 2003;42(4):728-35. 19. zanobetti m, poggioni c, pini r. can chest ultrasonography replace standard chest radiography for evaluation of acute dyspnea in the ed? chest journal. 2011;139(5):1140-7. 20. ang s-h, andrus p. lung ultrasound in the management of acute decompensated heart failure. current cardiology reviews. 2012;8(2):123. 21. kajimoto k, madeen k, nakayama t, tsudo h, kuroda t, abe t. rapid evaluation by lung-cardiac-inferior vena cava (lci) integrated ultrasound for differentiating heart failure from pulmonary disease as the cause of acute dyspnea in the emergency setting. cardiovasc ultrasound. 2012;10(1):49. 22. lichtenstein d, meziere g. a lung ultrasound sign allowing bedside distinction between pulmonary edema and copd: the comet-tail artifact. intensive care med. 1998;24(12):1331-4. 23. lichtenstein da, meziere ga. relevance of lung ultrasound in the diagnosis of acute respiratory failure: the blue protocol. chest. 2008;134(1):117-25. 24. gargani l. lung ultrasound: a new tool for the cardiologist. cardiovascular ultrasound. 2011;9(1):6. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 34 emergency (2016); 4 (1): 34-37 brief report patients’ attitude toward breaking bad news; a brief report hamed aminiahidashti1, seyed jaber mousavi2, mohammad mehdi darzi3* 1. department of emergency medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran. 2. department of community medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran. 3. faculty of medicine, mazandaran university of medical sciences, sari, iran. *corresponding author: mohammad mehdi darzi, student of medicine, department of emergency medicine, imam khomeini hospital, amir mazandarani bolivar, sari, iran. tel: +989113540546; email: samandarzi@yahoo.com. received: may 2015; accepted: september 2015 abstract introduction: delivering bad news is a stressful moment for both physicians and patients. the purpose of this investigation was to explore the patients’ preferences and attitudes toward being informed about the bad news. methods: this cross-sectional study was done on patients admitted to imam khomeini hospital, sari, iran, from september 2014 to february 2015. patient attitude regarding breaking bad news was evaluated using a reliable and valid questionnaire. results: 130 patients were evaluated (61.5% male, mean age = 46.21 ± 12.1 years). 118 (90.76%) participants believed that the patient himself/herself should be informed about the disease’s condition. 120 (92.30%) preferred to hear the news from a skillful physician and 105 (80.76%) believed that emergency department is not a proper place for breaking bad news. conclusion: based on the results of the present study, most participants believed that the most experienced and skillful physician should inform them completely regarding their medical condition. at the same time they declared that, it is best to hear bad news in a calm and suitable place and time rather than emergency department or hospital corridors during teaching rounds. keywords: truth disclosure; attitude; patient rights; ethics; physician-patient relations cite this article as: aminiahidashti h, mousavi sj, darzi mm. patients’ attitude toward breaking bad news; a brief report. emergency. 2016;4(1):34-37. introduction: he most famous and common definition of the bad news has been presented as “any news that adversely and seriously affects an individual’s view of his or her future”. a physician is expected to be able to disclose bad news and be responsible for patients’ request in this regard. how the bad news is given to the patients affects their interpretation of the disease (1). most physicians do not have previous experience in talking to patients about death or end-stage diseases and are required almost daily to give unwelcome news without being properly prepared for such instances (2). delivering bad news is a stressful moment for both physicians and patients (3, 4). people with different cultural backgrounds may show different attitudes toward disclosing bad news. in north america and europe, most physicians express the diagnosis obviously, but in south and east europe and china, some patients are excluded from receiving information about their disease (5, 6). the purpose of this investigation was to explore the patients’ preferences and attitudes toward being informed about the bad news. methods: this cross-sectional study was done on patients admitted to imam khomeini hospital, sari, iran, from september 2014 to february 2015. before beginning the project, questionnaire and the aim of study were explained to the participants and informed consent was obtained from them. the study protocol was confirmed by ethical committee of mazandaran university of medical sciences and researchers adhered to helsinki declaration during the study period. the studied population consisted of all patients above the age of 18 who were admitted with definite diagnosis of a malignant or chronic disease. exclusion criteria were refusing participation, disability to talk and communicate, and presence of cognitive disorders. the sample size was estimated to be 102 persons considering d = 0.1, z = 1.96, and p = 0.5 (7). a valid (cronbach’s alpha coefficient was 0.88) and reliable questionnaire consisting of demographic data and 30 questions was used for data gathering (table1). results: 138 patients participated in this study and 130 patients t this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 35 emergency (2016); 4 (1): 34-37 completed the questionnaire and returned it (61.5% male). the mean age of the included patients was 46.21 ± 12.1 years. 93 patients (71.5%) were married, 18 (13.84%) widowed, 12 (9.23%) single, and 7 (5.8%) divorced. among the patients, 67 (51.53%) had cancer, 21 (16.15%) end-stage renal disease (esrd), 18 (13.84%) hepatic cirrhosis, 17 (13. 07%) chronic obstructive pulmonary disease (copd) and 7 (5.38%) had other chronic diseases. the attitudes of patients toward breaking bad news is shown in table 1. discussion: in this study, 90.76% of patients believed they should be informed about their ongoing medical condition and receive the unwelcome news. similarly, in other studies done in china and australia, 83% and 77% of patients, respectively, believed they should be completely aware of their medical condition (8, 9). in our study, 56.15% of the patients were eager to be accompanied by someone while receiving bad news. furthermore, 45.38% of our participants preferred receiving bad news from their families while only 15.38% wanted to hear it from their second degree relatives or friends. studies in japan showed that 78% of patients prefer to share the bad news with their families (1). in australia, 57% of patients liked to have their families beside them while unwelcome news is disclosed (9). in contrast, some other studies showed that many patients prefer not to tell their families about having cancer (8). it was revealed that 81% of american patients like to be alone while receiving bad news (10). this study also showed that families have a helpful and supportive role at the time of unwelcome news disclosure and they can help patients accept the situation (7). moreover, our patients generally deemed a highly experienced rendering specialist to be the best person to break the bad news to them and they did not accept other medical staff or medical students for this purpose. this result is similar to findings of researches done in australia and portugal, which showed that only 13% and 0% agreed to receiving bad news from nurses or hospital staff, respectively (5, 9). similar to our findings, most studies showed that the treating table 1: patients’ attitude toward breaking bad news questions answers n (%) agree no idea disagree the patient should be completely aware of his/her medical condition. 118 (90.76) 6 (4.61) 6 (4.61) people accompanying the patient should be informed about the medical condition. 73 (56.15) 23 (17.69) 34 (26.15) family physician is the most suitable person for breaking the bad news. 14 (10.76) 59 (45.38) 57 (43.84) it is better if family members disclose the bad news (brother, sister, …) 59 (45.38) 26 (20) 45 (34.61) it is better if patient’s relatives or friends disclose the bad news. 20 (15.38) 25 (19.23) 85 (65.38) it is better if nurses or other medical staff disclose the bad news. 3 (2.30) 13 (10) 114 (87.76) specialist physician is the appropriate person to break the bad news. 115 (88.46) 9 (6.92) 6 (4.61) medical students are the appropriate people to break the bad news. 1 (0.76) 16 (12.30) 113 (86.92) giving the bad news during medical teaching round is suitable. 1 (0.76) 18 (13.84) 111 (85.38) hospital corridor is a suitable place for giving bad news. 3 (2.30) 19 (14.61) 108 (83.07) a private retired room is suitable for giving bad news. 68 (52.30) 51 (29.23) 11 (8.46) it is better to disclose bad news right after confirmation of diagnosis. 33 (25.38) 55 (42.30) 42 (32.30) emergency room is a suitable place for giving bad news. 8 (6.15) 17 (13.07) 105 (80.76) an aged physician is a more appropriate person to break the bad news. 102 (78.46) 16 (12.30) 12 (9.23) i like to be informed about the cause of my disease. 85 (65.38) 34 (26.15) 11 (8.46) i like to be totally informed about my ongoing medical condition and its prognosis. 76 (58.46) 47 (36.15) 7 (5.38) it is good to have some information about a medical condition before hearing bad news. 81 (62.30) 38 (29.23) 11 (8.46) it is better for the doctor to know how much the patient knows about that medical condition. 87 (66.92) 38 (29.23) 5 (3.84) receiving bad news about a common disease is much easier than hearing about a rare disease. 108 (82.30) 20 (15.38) 3 (2.30) physician’s skill in treatment affects compliance of receiving bad news. 120 (92.30) 9 (6.92) 1 (0.76) medical condition awareness positively influences continuing a medical treatment. 102 (78.46) 27 (20.76) 1 (0.76) it is better to educate doctors about how to disclose bad news. 66 (50.76) 63 (48.46) 1 (0.76) availability of psychology consultant is necessary at the time or after disclosure of bad news. 80 (61.53) 45 (34.61) 5 (3.84) i would like to talk with a religious consultant after hearing a bad news. 66 (50.76) 50 (38.46) 14 (10.76) doctors should consider the psychological status of patients while breaking bad news. 100 (76.92) 21 (16.15) 9 (6.92) doctors should consider patients’ religious beliefs while breaking bad news. 90 (69.23) 26 (20) 14 (10.76) breaking of bad news by doctors makes patients pessimistic about their treatments. 31 (23.84) 80 (61.53) 19 (14.61) it is the patient’s right to know everything about his/her medical condition. 98 (75.38) 30 (23.07) 2 (1.53) cancer patients should be informed about their disease. 70 (53.84) 17 (13.07) 43 (33.07) cancer patients should be completely informed about their ongoing medical condition and their life expectancy. 84 (64.61) 16 (12.30) 30 (23.07) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com aminiahidashti et al 36 physician is the best person to convey unwelcome messages (5, 11). a proper doctor-patient relationship in breaking bad news can enhance patient’s compliance in treatment and stress management (12, 13). many studies showed that doctors did not have enough self-confidence and skill for breaking unwelcome news and were unable to handle patients’ reactions and emotions (14, 15). in this survey, 50.76% of patients believed that doctors needed education about bad news disclosure, which shows the necessity of skill achievement for doctors and medical students regarding this issue. therefore, it is highly recommended to make a plan and educate doctors for becoming skillful in communicating with patients especially for giving bad news and handling their different reactions toward the news. this study demonstrated that 83.07% and 80.76% of patients did not want to receive bad news in hospital corridors and emergency room, respectively. also, 52.30% of them emphasized that this should be done in a private retired room. in a study by alrukban et al. 68% of people believed it was necessary to convey unwelcome messages in a private place (16). other studies have also emphasized this issue (17, 18). the participants of our study stated that they needed psychological and religious consultations after receiving unwelcome messages and physicians should pay attention to their religious and emotional conditions in this situation. few studies have been done regarding this point (19, 20). in our study, 75.38% of patients affirmed that they should be thoroughly informed about their disease and the majority of them desired to know the cause, progress and prognosis of their disease. knowing life expectancy was crucial for cancer patients. participants of all the studies done in asia and western countries declared that it is their right to know all details of their diseases (5, 10, 16). breaking bad news to patients demands more consideration for cultural and personal status of patients and it should be done by the treating specialist privately. educational workshops are needed for medical staff concerning this topic. it is recommended to design a standard questionnaire considering numerous factors cultural status of the area and status of medical services to achieve more accurate results. conclusion: based on the results of the present study, most participants believed that the most experienced and skillful physician should inform them completely regarding their medical condition while considering patients’ psychological status. at the same time they declared that, it is best to hear bad news in a calm and suitable place and time rather than emergency department or hospital corridors during teaching rounds. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. fujimori m, akechi t, morita t, et al. preferences of cancer patients regarding the disclosure of bad news. psychooncology. 2007;16(6):573-81. 2. orlander jd, graeme fincke b, hermanns d, johnson ga. medical residents' first clearly remembered experiences of giving bad news. journal of general internal medicine. 2002;17(11):825-40. 3. buckman r. breaking bad news: why is it still so difficult? bmj. 1984;288(6430):1597-9. 4. ptacek j, eberhardt tl. breaking bad news: a review of the literature. jama. 1996;276(6):496-502. 5. gonçalves f, marques á, rocha s, leitão p, mesquita t, moutinho s. breaking bad news: experiences and preferences of advanced cancer patients at a portuguese oncology centre. palliative medicine. 2005;19(7):526-31. 6. tse c, chong a, fok s. breaking bad news: a chinese perspective. palliative medicine. 2003;17(4):339-43. 7. managheb se, hosseinpour m, mehrabi f. patient’s viewpoints about how to break bad news. iranian journal of medical ethics and history of medicine. 2013;6(4):68-79. 8. li j, gao xh, yang xm, jing p, yu sy. whether, when, and who to disclose bad news to patients with cancer: a survey in 150 pairs of hospitalized patients with cancer and family members in china. psycho-oncology. 2012;21(7):778-84. 9. butoco p, kazemi u, beeney i. when the diagnosis is cancer: patient communication experience and preferences. cancer. 1996;77:2630-7. 10. kim mk, alvi a. breaking the bad news of cancer: the patient's perspective. the laryngoscope. 1999;109(7):1064-7. 11. tang st, liu t-w, lai m-s, liu l-n, chen c-h, koong s-l. congruence of knowledge, experiences, and preferences for disclosure of diagnosis and prognosis between terminally-ill cancer patients and their family caregivers in taiwan. cancer investigation. 2006;24(4):360-6. 12. ptacek j, ptacek jj. patients’ perceptions of receiving bad news about cancer. journal of clinical oncology. 2001;19(21):4160-4. 13. cameron c. patient compliance: recognition of factors involved and suggestions for promoting compliance with therapeutic regimens. journal of advanced nursing. 1996;24(2):244-50. 14. thomsen oo, wulff hr, martin a, singer p. what do gastroenterologists in europe tell cancer patients? the lancet. 1993;341(8843):473-6. 15. konstantis a, exiara t. breaking bad news in cancer patients. indian journal of palliative care. 2015;21(1):35. 16. alrukban mo, albadr bo, almansour m, et al. preferences and attitudes of the saudi population toward receiving medical bad news: a primary study from riyadh city. journal of family & community medicine. 2014;21(2):85. 17. sutherland hj, llewellyn-thomas ha, lockwood ga, tritchler dl, till je. cancer patients: their desire for this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 37 emergency (2016); 4 (1): 34-37 information and participation in treatment decisions. journal of the royal society of medicine. 1989;82(5):260-3. 18. fujimori m, uchitomi y. preferences of cancer patients regarding communication of bad news: a systematic literature review. japanese journal of clinical oncology. 2009;39(4):20116. 19. ford s, fallowfield l, lewis s. can oncologists detect distress in their out-patients and how satisfied are they with their performance during bad news consultations? british journal of cancer. 1994;70(4):767. 20. girgis a, sanson-fisher rw. breaking bad news: consensus guidelines for medical practitioners. journal of clinical oncology. 1995;13(9):2449-56. emergency. 2017; 5 (1): e49 le t t e r to ed i to r predatory journals and perished articles; a letter to editor mashallah narimani1, mehdi dadkhah2∗ 1. independent researcher on library and information science, isfahan, iran. 2. independent scientist, information science and publication ethics scholar, isfahan, iran. received: june 2016; accepted: june 2016; published online: 14 january 2017 cite this article as: nariman m, dadkhah m. predatory journals and perished articles; a letter to editor. emergency. 2017; 5(1): e49. in recent years, academic publishing has been faced with many destructive phenomena. “predatory publishers” (or journals) are one challenge for scholarly publishing. this term was introduced to academic societies for the first time by jeffrey beall in 2010 (1). a predatory journal is a journal which publishes papers without peer review, or by an unfair review process and charging publication fees (2). according to beall’s definition, questionable peer review process and unknown location of the real controlling entity are among the most important criteria for detecting predatory journals (3). in 2016, beall announced that the number of predatory publisher was growing (4) from 18 in 2011 to 923 in 2016 (figure 1). these statistics convince researchers of the need for more research into dealing with predatory journals. predatory journals have little or no peer review, thus they will be a repository for false principles and bogus research (1). these bogus researches may be dangerous in some domains such as medical sciences, especially emergency medicine. in some countries, the number of published papers are more important than their quality (5). in this situation, predatory authors will publish bogus papers in such journals. unwary researchers may use published papers in predatory journals for their research and it will lead to establishing their own research based on such previous bogus research. by mining the most recent beall’s list of predatory journals (6), we found that there are 56/1080 (5%) predatory medical journals in his list. it is necessary to state that many fraudulent journals have general domains and publish papers in the medical science domain as well, so we can find many predatory journals and bogus research related to emergency medicine. however, some predatory journals have reputable indexing and their published papers will be indexed in scientific databases. ∗corresponding author: mehdi dadkhah; isfahan, iran. email: dadkhah80@gmail.com, tel: +989397379692 . figure 1: number of predatory publisher from 2011 until 2016 (4). predatory publishers are in the habit of sending huge number of “call for papers” emails to receive papers from authors. in this condition, naive authors will submit their paper to these journals and, as a consequence, predatory journals grow every day. it is necessary to establish a suitable educational plan for confronting fraudulent journals. in recent years, the growth rate of such journals has increased, but the number of new registered journals do not appear to have high growth. figure 2 shows the number of predatory publishers, standalone predatory journals and predatory medical journals (specifically publishing papers about emergency medicine) from 2011 until 2016 (7). according to this figure, we can conclude that predatory journals and publishers have rapid growth. in conclusion, the best method for dealing with predatory journals is a good educational plan and increasing the awareness of authors about the problem (8). authors must avoid submitting papers to journals that promise fast publishing by receiving publication charges. table 1 shows the main criteria for detection of predatory medical journals. to that end, we extracted these main criteria from beall’s criteria for predatory journal detection (3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. dadkhah et al. 2 table 1: main criteria for detection of predatory medical journals no. criteria description 1 contact information email addresses of editors are not available and journal uses general email services such as yahoo or google. 2 publication charges journal uses different types of charges such as publication charges, page charges, author’s charges, fast track charges. 3 similar names journal uses a name similar to standout and popular medical journals to confuse authors and cheat them. 4 bogus metric journal claims that it has an impact factor, but it is not indexed in thomson reuters web of science and uses bogus metrics such as global impact factor (gif), scientific indexing service (isi), etc. 5 call for paper journal sends a huge number of spam emails to receive paper from authors. in these call for papers, journal claims that it has a high impact factor and is indexed in valid databases. some journals have a general name such as “academic research. ..” and publish papers in medical sciences. 6 review and publishing process the process of review and publishing is not clear and paying publication charges is more important than quality and publishing standards. 7 number of published papers the journal publishes many papers in each issue and most of them are outside of journal’s aim and scope. figure 2: number of predatory publishers, standalone predatory journals and predatory medical science journals from 2011 until 2016 (7). references 1. beall j. medical publishing triage-chronicling predatory open access publishers. annals of medicine and surgery. 2013;2(2):47-9. 2. lukic t, blesic i, basarin b, ivanovic b, milosevic d, sakulski d. predatory and fake scientific journals/publishers-a global outbreak with rising trend: a review. geographica pannonica. 2014;18(3):69-81. 3. beall j. criteria for determining predatory open-access publishers. scholarly open access https://scholarlyoa files wordpress com/2015/01/criteria-2015 pdf,(accessed 2015-02-14). 2015. 4. beall j. beall’s list of predatory publishers, scholarly open access [cited 2016 14 april]. available from: https://scholarlyoa.com/2016/01/05/bealls-list-ofpredatory-publishers-2016/. 5. simon a. pitfalls of predatory journals: a personal account. comprehensive psychology. 2016;5:1-5. 6. harzing a-w. publish or perish. 2007. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e49 7. beall j. beall’s list of stand alone journals, scholarly open access [cited 2016 14 april]. available from: https://scholarlyoa.com/individual-journals/. 8. clark j, smith r. firm action needed on predatory journals. bmj. 2015;350:h210. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com references emergency. 2017; 5 (1): e67 ca s e re p o rt accidental chronic poisoning with methotrexate; report of two cases reza bidaki11,2∗, mojgan kian3, hamid owliaey4, mojtaba babaei zarch5, masoud feysal6 1. research center of addiction and behavioral sciences, shahid sadoughi university of medical sciences, yazd, iran. 2. diabetes research center, shahid sadoughi university of medical sciences, yazd, iran. 3. department of psychiatry, shahid sadoughi university of medical sciences, research center of addiction and behavioral sciences, yazd, iran. 4. fellowship of toxicity, assistant professor of islamic azad university of yazd, yazd, iran. 5. student research committee, shahid sadoughi university of medical sciences, yazd, iran. 6. school of medicine. shahid sadoughi university of medical sciences, yazd, iran. received: december 2016; accepted: february 2017; published online: 21 may 2017 abstract: methotrexate has been used widely in dermatology, oncology and rheumatology fields. however, methotrexateinduced mucocutaneous lesions may occur in rare cases. in this case presentation, we report two cases of accidental poisoning with methotrexate. they had accidentally used methotrexate instead of digoxin. this case report emphasizes that early diagnosis and appropriate management is critical in order to improve outcome. keywords: methotrexate; skin ulcer; toxicity; poisoning; case reports; emergency treatment © copyright (2017) shahid beheshti university of medical sciences cite this article as: bidaki r, kian m, owliaey h, babaei zarch m, feysal m. accidental chronic poisoning with methotrexate; report of two cases. emergency. 2017; 5 (1): e67. 1. introduction methotrexate (mtx) is a systemic immunosuppressive agent that was introduced in the 1950s (1, 2). it is a folate antimetabolite that binds to an enzyme named dihydrofolate reductase, which ultimately leads to inhibition of dna synthesis (3, 4). mtx is a drug used in treatment of various malignancies, early ectopic pregnancy or chronic inflammatory diseases such as some types of carcinoma, rheumatoid arthritis, psoriasis and etc. (5, 6). accidental poisoning with mtx is not a common condition and was rarely reported in the literature (7). most of our knowledge regarding mtx poisoning were derived from serious adverse reactions at therapeutic doses or reports about acute oral overdose (8). unlike previously reported cases, here we report two cases of accidental chronic poisoning with mtx. ∗corresponding author: reza bidaki; research center of addiction and behavioral sciences, shahid sadoughi university of medical sciences, yazd, iran; tel: +983532633555; email: reza_bidaki@yahoo.com 2. case report 2.1. case 1 the patient was an 88-year-old woman. she was admitted to the emergency department with weakness as main chief complaint. she had dyspnea, gastrointestinal symptoms such as nausea and vomiting, abdominal pain, dyspepsia, pruritus, epistaxis, and mouth sores from 3 days ago. the symptoms were progressive. in evaluation of consumed drugs it was determined that she has been continuously taking mtx for about 5 months. in search for the cause of taking mtx and checking the prescriptions, it was revealed that the drug store had mistakenly given the patient mtx instead of digoxin. she had used mtx 1.25 mg for 5 consecutive months and 2.5 mg five days a week in the last month. on admission, her vital signs were as follows: blood pressure = 90/60 mmhg, pulse rate = 82/minutes, respiratory rate = 12/minutes and temperature = 38.2◦c. on physical examination, generalized erythema involving back and leg, face edema, mucositis, stomatitis and difficulty in gait were apparent. examination of other organs did not reveal any positive findings. figure 1 shows her mucocutaneous lesions at presentathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. bidaki et al. 2 figure 1: mucocutaneous lesions in case number 1. tion. laboratory test results on admission were as follows: hemoglobin=9.1 g/dl, wbc=3200/mm3, platelet counts = 50000/mm3, bun = 81 mg/dl, creatinine=1.8 mg/dl, ast=18 iu/l, alt=17 iu/l, pt=14s, ptt=36s, inr=1.14, bilirubin total=1.2 mg/dl and bilirubin direct=0.3 mg/dl. she was admitted to intensive care unit (icu). platelets, folinic acid (as mtx antidote), antibiotics and granulocyte colony stimulating factor (g-csf) were administered and dermatology cares were considered for her. finally, she died due to pulmonary edema resulting from her underlying cardiac disease 4 days after admission. 2.2. case 2 the patient was a 68-year-old woman, who was referred to the emergency department because of oral ulcer, limb paresthesia and difficulty initiating movement from one week ago. muscular force was reduced gradually. the patient didn’t have any history of trauma. the patient had accidentally used one mtx tablet each day, instead of digoxin, since one month ago (due to a mistake in the drug store, she was given mtx instead of digoxin). in the past medical history, the patient had a history of diabetes mellitus, hypertension, heart failure and hyperlipidemia. other drugs used by the patient included losartan, aspirin, carvedilol, l-carnitine and triamterene-h. on admission, she was alert and her vital signs were as follows: blood pressure = 110/70 mmhg, pulse rate = 74/minute, respiratory rate =16/minute and temperature = 36.8◦c. on physical examination, level of consciousness was normal. there was no evidence of respiratory distress. neurological examinations revealed normal cerebellar tests. upper limb muscular force was normal and lower limb force was 4/5 in proximal and 3/5 in distal. hemorrhagic ulcers were seen in palate and lips. figure 2 shows her mucocutaneous lesions at presentation. laboratory tests were as follows: hemoglobin=11.2 g/dl, wbc=10.9/mm3, platelet counts = 20000/mm3, natrium = 140 meq/l, potassium = 3.5 meq/l, urea=36 mg/dl, creatinine=0.85 mg/dl, pt=13 s, ptt=27 s, inr=1.3, alt=43 iu/l, ast=34 iu/l, alp=200 iu/l. magnetic resonance imaging (mri) and also electromyogram/nerve conduction velocity (emg/ncv ) tests were normal. echocardiography revealed ejection fraction (ef) of 20%. with diagnosis of mtx poisoning, the patient underwent treatment with folinic acid for 10 days. the patient was discharged with good general condition and improvement of weakness and lower limb paresthesia 5 days later. 3. discussion mtx toxicity is characterized by nausea, vomiting, diarrhea, myelosuppression, pancytopenia, liver dysfunction, acute renal failure (arf), pulmonary symptoms, mucositis, stomatitis, ulceration/erosion of the gastrointestinal system and cutaneous ulcerations (9-11). although methotrexate toxicity can cause kidney injury and change the renal function, sometimes renal dysfunction like an acute renal failure can also induce methotrexate toxicity (4, 12-14). however, cutaneous ulceration may be considered as an early clinical sign of imminent systemic toxicity and patients may only present with isolated cutaneous lesions (15-17). the side effects of mtx may occur through dose dependent or idiosyncratic mechanisms. interestingly, dose dependent mechanism occurs in bone marrow cells, epidermal cells and epithelial gastrointestinal system. some factors such as drug interactions and incorrect administration of drugs are triggers for appearance of side effects (9). simultaneous use of mtx with drugs interacting with it such as proton-pump inhibitors, trimethoprim/sulfamethoxazole, doxycycline, non-steroidal anti-inflammatory drugs (nsaids), and salicylates that decrease protein binding or reduce renal clearance, as well as excessive alcohol consumption could play an important role in this regard (18). elevation of serum aminotransferase levels, elevation in serum uric acid, leukopenia, thrombocytopenia, and anemia may be noticed in laboratory tests of mtx poisoned patients (19). measurement of methotrexate concentration via radioimmunoassay in plasma, serum, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e67 figure 2: mucocutaneous lesions in case number 2. or urine samples could lead to definite diagnosis (19). diagnostic biopsy from ulceration sites is rarely required, but helpful (2). withdrawal of mtx and administration of intravenous folinic acid (leucovorin) as early as possible after exposure is the most effective initial treatment that should not be delayed for any reason (2, 19). treat persistent nausea and vomiting with several antiemetic agents such as metoclopramide, ondansetron, promethazine, haloperidol, benzodiazepines, or even corticosteroids. intravenous fluids and urine alkalization via bicarbonate infusion are highly advised. administration of colony stimulating factors is necessary if severe neutropenia exists. transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia, or hemorrhage. the patient should be closely monitored for signs of bleeding, clinical evidence of infection, abnormalities in serum electrolytes, renal failure and hepatic function. a chest radiograph should be obtained in patients with respiratory symptoms and skindirected therapy must to be applied (19). in patients with impaired renal function who develop toxicity and in cases of acute overdose, glucarpidase has been used to rapidly catabolize mtx to an inactive metabolite, aiding its clearance (2, 19, 20). although mtx toxicity can be a fatal poisoning, proper management, early diagnosis and follow-up of the patients in emergency department as well as in icu can resolve the complications and save the patients’ lives. it seems that computerized prescription system is a promising method to reduce human errors. 4. appendix 4.1. acknowledgements the authors thank the families of patients and nurses of internal medicine department and icu of shahid beheshti hospital, taft, iran for their cooperation. 4.2. authors contribution all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data collection and interpretation. 4.3. conflict of interest all authors declare that there is no conflict of interest in this study. 4.4. funding all authors declare that this study was accomplished without any funding or support. references 1. shen s, o’brien t, yap lm, prince hm, mccormack cj. the use of methotrexate in dermatology: a review. australasian journal of dermatology. 2012;53(1):1-18. 2. weidmann a, foulkes ac, kirkham n, reynolds n. methotrexate toxicity during treatment of chronic plaque psoriasis: a case report and review of the literature. dermatology and therapy. 2014;4(2):145-56. 3. tripathi r, chugh pk, verma v, mala ym. fatal methotrexate toxicity: could it have been avoided? bmj case reports. 2013;2013. 4. cudmore j, seftel m, sisler j, zarychanski r. methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur. canadian family physician medecin de famille canadien. 2014;60(1):53-6. 5. czarnecka-operacz m, sadowska-przytocka a. the possibilities and principles of methotrexate treatment of psoriasis the updated knowledge. postepy dermatologii i alergologii. 2014;31(6):392-400. 6. drug information for the health care professional. 24 ed: thomson micromedex; 2004. 1911 p. 7. souza c, suarez o, silva t, gorenstein a, quintella l, avelleira j. ulcerations due to methotrexate toxicity in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. bidaki et al. 4 a psoriasis patient. anais brasileiros de dermatologia. 2015;91(3):375-7. 8. chan bs, dawson ah, buckley na. what can clinicians learn from therapeutic studies about the treatment of acute oral methotrexate poisoning? clinical toxicology. 2017;55(2):88-96. 9. tan kw, tay yk. a case of acute methotrexate toxicity. annals of the academy of medicine, singapore. 2011;40(2):97-9. 10. jakubovic bd, donovan a, webster pm, shear nh. methotrexate-induced pulmonary toxicity. canadian respiratory journal : journal of the canadian thoracic society. 2013;20(3):153-5. 11. shiver mb, hall la, conner kb, brown ge, cheung wl, wirges ml. cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity. dermatology online journal. 2014;20(7). 12. chatham ww, morgan sl, alarcon gs. renal failure: a risk factor for methotrexate toxicity. arthritis and rheumatism. 2000;43(5):1185-6. 13. soon c, ilchyshyn a. methotrexate toxicity induced by acute renal failure. journal of the royal society of medicine. 2005;98(2):83-4. 14. strang a, pullar t. methotrexate toxicity induced by acute renal failure. journal of the royal society of medicine. 2004;97(11):536-7. 15. lawrence c, dahl m. two patterns of skin ulceration induced by methotrexate in patients with psoriasis. journal of the american academy of dermatology. 1984;11(6):1059-65. 16. caliskan e, tunca m, acikgoz g, arca e, akar a. accidental high-dose methotrexate toxicity due to an electronic prescribing error. indian journal of dermatology, venereology and leprology. 2013;80(3):268-9. 17. kocak a, kocak o, aslan f, tektas m. methotrexate toxicity presenting as cutaneous ulcerations on psoriatic plaques. cutaneous and ocular toxicology. 2013;32(4):333-5. 18. bourre-tessier j, haraoui b. methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. the journal of rheumatology. 2010;37(7):1416-21. 19. hsdb: methotrexate u.s. national library of medicine: toxnet. available from: https://toxnet.nlm.nih.gov/cgibin/sis/search2/r?dbs+hsdb:@term+@docno+3123. 20. tuffaha h, al omar s. glucarpidase for the treatment of life-threatening methotrexate overdose. drugs of today (barcelona, spain: 1998). 2012;48(11):705-11. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 40 emergency (2014); 2 (1): 40-42 original research treatment costs of traffic accident casualties in a third-level hospital in iran; a preliminary study mohammad manouchehrifar1, hamid reza hatamabadi2, niloufar derakhshandeh3* 1. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran 3. department of pediatrics, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: the costs of traffic accidents in lowand middle-income countries are estimated to add up to $65 billion annually, which is a little higher than the amount they receive as a final aid for development. the present retrospective study aims to evaluate the treatment costs of the hospitalized injured individuals in traffic accidents. methods: the present study was carried out in imam hossein hospital, tehran, iran. the study population consisted of all the individuals injured in traffic accidents, admitted to the hospital wards. data were collected by a trained emergency physician. demographic data, injury mechanism, the type of vehicle, the admission ward of the patient, and treatment costs were collected. results: 200 patient files were evaluated (males: 89%). the results showed that 54% of the patients were in the 18-40-year age group and collisions between cars and motorcycles were the most frequent accidents (47%). the mean hospitalization cost for each patient was estimated to be $1622.1. statistical analyses showed that treatment costs in the neurosurgery ward was significantly higher than orthopedic and general surgery (df: 3; f=9.5, p=0.008). conclusion: the results of the present study showed that the mean cost of each traffic accident victim in tehran is approximately $1622.1 and these patients sustain significantly higher costs in neurosurgery ward. key words: health care costs; traffic accidents; hospitalization cite this article as: manouchehrifar m, hatamabadi hr, derakhshandeh n. treatment costs of traffic accident casualties in a third-level hospital in iran; a preliminary study. emergency. 2014;2(1):40-2. introduction: 1 oad traffic injuries (rti) are one of the most important health care problems all over the world; in this context, such accidents result in the death of 1.2 million people and the injury of 50 million ones annually. unfortunately, more than 90% of deaths due to road traffic accidents occur in lowand middleincome countries (1, 2). it is predicted that if such a trend continues, in the next five years road traffic accidents will result in the death of 6 million people and the injury of 60 million individuals only in developing countries. in 1990, road accidents ranked ninth in the list of the most important factors threatening the health of the community; but it is predicted that by 2020 they will rank the third cause of mortality and morbidity. another bitter fact about these reports is that 50% of the killed are individuals aged between 15‒43 years-old, who are the most important group in the economic development of societies (3). social and economic costs of road accidents and their physical and psychological adverse effects on individuals and communities are the most important problems encountered by specialists, *corresponding author: niloufar derakhshandeh; department of pediatrics, loghman hakim hospital, makhsoos ave, tehran, iran. tel: +989136470851; fax:+982122721155 email: arashmanouchehrifar@yahoo.com received: 5 january 2014; accepted: 7 february 2014 authorities of transportation industry, and health systems. the number of road accidents rises in developing countries and the direct and indirect costs are higher compared to those in developed countries (4). unfortunately, iran has a high rate of road traffic accidents and the incidence of fatal rtis in iran is 33 in 100,000 of the population (5). this high incidence rate shows the importance of more research and adoption of efficacious preventive and therapeutic measures in the management of road traffic accidents. based on estimations, the global costs of road traffic accidents is $518 billion annually, with $65 billion in lowand middle-income countries, which is a little higher than the financial aid they receive for development (6). studies by the world bank show that the number of people dying due to road traffic accidents in iran has increased by 10%, which is higher than that in many developing countries and is very undesirable and worrying based on world standards (1). a correct estimate of the economic and social consequences of road traffic accidents is not available in lowand middle-income countries. thus, based on world health organization (who) latest report, further research is necessary on the epidemiologic pattern of road traffic accidents in such countries to determine the extent of the problem and identify individuals susceptible to traffic accidents. in this regard, iran is not an exception as a lowand middle-income country (2). altr mailto:arashmanouchehrifar@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 41 manouchehrifar et al hough valuable efforts have been made in recent years in iran to estimate the burden of such accidents and their consequences (7-9), there are still insufficient data in this respect. therefore, the present retrospective study was undertaken to evaluate the therapeutic costs of road traffic accidents and injuries in individuals admitted into hospital wards in a third-level hospital in iran. methods: study design the present cross-sectional study was carried out in the third-level imam hossein hospital in tehran, iran, retrospectively. tehran is the capital and largest city in iran with a population of approximately 13 million people. the study was carried out from august 2008 to august 2009. the study population consisted of all the road traffic victims hospitalized in imam hossein hospital during the one-year period mentioned above, who had an accident with at least one vehicle. the exclusion criteria were the lack of access to the patient data on age, deficiencies in patient file, and pedestrians’ falls without involvement of a vehicle. selection of samples was carried out randomly from the files of hospitalized patients. to this end, the list of all the road accident victims were sorted based on hospitalization code and then randomization table was used to select 200 patient files, randomly. data collection data were collected using a checklist consisted of demographic data (age and gender), the mechanism of injury, the type of vehicle, the hospitalization ward, and the patient’s treatment costs. data were collected by a trained emergency physician. the instructions were given to the physician included the management of research tools (how to complete the checklist, registration of data), and summarization of medical data. the traffic accident victims, included in the study, were irrespective to the severity of injuries. data were extracted from the files of hospitalized patients. statistical analysis data were analyzed with spss 20. quantitative data were reported as means and standard deviations; qualitative data as frequencies and percentages. one-way anova and tukey post hoc were used to compare treatment costs separately in each ward. statistical significance was defined as p<0.05. results: 200 patient files were evaluated in the present study (male: 89%), with 54% of the victims in the 18‒40age group. motorcycle accidents (47%) were the most frequent accidents (figure 1), with 66% of the patients hospitalized in the orthopedic ward, 20% in the neurosurgery and 14% in the general surgery (table 1). the mean hospitalization cost was estimated at $1622.1, with the highest hospitalization costs in the neurosurgery ward ($2192.1), followed by orthopedic ($1487.4) and general surgery ($1186.85) (figure 2). the therapeutic costs of hospitalized patients in the neurosurgery ward were significantly higher than those in other wards (df: 3; f=9.5; p=0.008). discussion: the results of the present study showed that the mean treatment cost for patients injured in road traffic accidents is $1622.1 for each patient in a third-level educational hospital with 5000 admissions monthly in tehran. the cost is significantly higher in the neurosurgery ward compared to other wards. in addition, motorcycle accidents were the most frequent events leading to hospitalization. in this context, a study by razaei et al. can be mentioned in which the mean hospital cost for traffic accident victims was reported to be $1370 for each patient (9). in relation to patients’ treatment costs it should be pointed out that even patients succumbing to death, inflict high hospital costs on health systems. the annual mortality rate of traffic accidents in iran has been reported to be 44 in 100,000 of the population, which is higher than the death toll of an earthquake in bam in 2003 (10, 11). data available in iran show that the treatment costs of an injured individual who finally succumbs to death is $2410 on the average (9). therefore, a high rate of mortality and treatment costs of the victims impose heavy financial burdens on health service systems. on the other hand, costs related to physiotherapy and rehabilitation of victims and incidence of persistent debilities result in direct and indirect financial burdens (9). however, since the health system in iran should pay all the costs of traffic accident victims, the overall treatment costs of these patients are very high. for example, rezaei et al. showed that the treatment costs inflicted by traffic accident victims in tehran is around $336 million annually (9). in addition, a study in barcelona showed that treatment costs of road traffic accidents are almost $329 million annually (12). therefore, programming and preparation of preventive strategies for road accidents should be pursued as fast as possible. finally, it is suggested that a registry of road table 1: the variables evaluated in the patients  variable frequency )%( age (year) 18≤ 30 (15) 19-40 108 (54) 41-59 44 (22) 60≥ 18 (9) gender male 178 (89) female 22 (11) hospitalization ward orthopedic 132 (66) neurosurgery 40 (20) general surgery 28 (14) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 42 emergency (2014); 2 (1): 40-42 traffic deaths and injuries should devised and created to determine risk factors, conditions, and chain of events leading to accidents. such comprehensive descriptions are seldom achievable with local reporting systems (13, 14). this will help determine the country’s health system priorities. conclusion: the results of the present study showed that the mean treatment cost of a traffic accident victim in a thirdlevel hospital in tehran is around $1622.1, with the highest costs for patients in the neurosurgery ward. acknowledgments: we acknowledge all staffs of imam hossein hospital, tehran, iran. conflict of interest: none funding support: none authors’ contributions: manouchehri m and drakhshandeh n had contributed in all parts of study as designing, data gathering, data analysis, and development of the article. references: 1. peden m, scurfield r, sleet d, et al. world report on road traffic injury prevention. geneva: world health organization 2004. 2. world health organization. global status report on road safety: time for action. geneva: world health organization. 2009. 3. world health organization. world health statistics 2009. genova: world health organization; 2009. 4. ghaffar a, hyder aa, masud ti. the burden of road traffic injuries in developing countries: the 1st national injury survey of pakistan. public health. 2004;118(3):211-7. 5. saadat s, soori h. epidemiology of traffic injuries and motor vehicles utilization in the capital of iran: a population based study. bmc public health. 2011;11(1):488. 6. dueck a, poenaru d, pichora dr. cost factors in canadian pediatric trauma. canadian journal of surgery. 2001;44(2): 117-23. 7. maracy m, isfahani mt. the burden of road traffic injuries in isfahan, iran in 2010. j kerman univer med sci. 2013;20 (5):505-19 [persian]. 8. moafian g, aghabeigi mr, heydari st, hoseinzadeh a, lankarani kb, sarikhani y. an epidemiologic survey of road traffic accidents in iran: analysis of driver-related factors. chinese j traumatol. 2013;16(3):140-4. 9. rezaei s, akbari sa, arab m, ghasempour s. economic burden of road traffic crashes in tehran province, iran in 2009. health inf manage. 2013;10(3):498-509 [persian]. 10. bhalla k, naghavi m, shahraz s, bartels d, murray c. building national estimates of the burden of road traffic injuries in developing countries from all available data sources: iran. inj prev. 2009;15(3):150-6. 11. najafi i, safari s, sharifi a, et al. practical strategies to reduce morbidity and mortality of natural catastrophes: a retrospective study based on bam earthquake experience. arch iran med. 2009;12(4):347-52. 12. garcía-altés a, pérez k. the economic cost of road traffic crashes in an urban setting. inj prev. 2007;13(1):65-8. 13. hatamabadi hr, vafaee r, haddadi m, abdalvand a, soori h. necessity of an integrated road traffic injuries surveillance system: a community-based study. traffic inj prev. 2011;12 (4):358-62. 14. hatamabadi h, vafaee r, haddadi m, abdalvand a, esnaashari h, soori h. epidemiologic study of road traffic injuries by road user type characteristics and road environment in irán: a community-based approach. traffic inj prev. 2012;13(1):61-4. figure 1: mechanisms of trauma in patients under study, consisting of vehicle turning over, mechanical and road faults, and driver fatigue.  figure 2: treatment costs separately for each ward. * shows significant difference from other groups at p<0.01.  47% 31% 16% 6% 0 10 20 30 40 50 60 motor-car accidents car-car accident pedestrian accident other p e r c e n ta g e o f p a ti e n ts mechanism of trauma * 0 500 1000 1500 2000 2500 3000 neurosurgery orthopedic general surgical c o s t (u s d o ll a r ) ward emergency. 2017; 5 (1): e65 ph oto qu i z a 41-year-old woman with seizure fatemeh mohammadi1, reza mosaddegh1, samira vaziri1∗ 1. emergency medicine management research center, iran university of medical sciences, tehran, iran. received: marchl 2017; accepted: april 2017; published online: 15 april 2017 cite this article as: mohammadi f, mosaddegh r, vaziri s. a 41-year-old woman with seizure. emergency. 2017; 5(1): e65 figure 1: axial cuts of brain ct scan without contrast. 1. case presentation the patient was a 41 year old woman that was brought to the emergency department (ed) by her husband following seizure. according to the relatives accompanying her, the seizure was of tonic-clonic type, had occurred one hour before presentation to ed, and had lasted 3 minutes. the patient had been drowsy for about 15 minutes after the end of the seizure. she had no history of head trauma and did not mention headache, nausea and vomiting, fever, vision problems or others. on presentation, amnesia regarding the things that happened was evident. in her history, she had a generalized tonic-clonic seizure 4 years back, regarding which she had not done proper follow up for taking necessary diagnostic measures and had not been treated with anti-epileptic medication. she had a history of surgery for removing cold thyroid nodule 20 years ago and was under calcium treatment for 15 years but she had decided to stop taking her medications since 5 year ago. she did not have a history of alcohol or drug abuse. the patient was conscious ∗corresponding author: samira vaziri; department of emergency medicine, firoozgar hospital, karimkhan street, valiasr square, tehran, iran. tel: 00989123546849; email: samira.vaziri@yahoo.com and awake on presentation and did not have any specific clinical complaints. her vital signs on presentation were as follows: blood pressure = 120/70mmhg, pulse rate = 68/minute, respiratory rate = 16/minute, o2saturation= 98% at air room, oral temperature= 37◦c, and bedside blood sugar in the normal range. in head and neck examination, the surgery scar was seen in the thyroid region. examination of the thyroid also showed a nodular surface in palpation. examination of the heart, lungs, abdomen and extremities did not have pathologic findings. neurologic examinations including evaluation of cranial nerves, sense and power of the muscles, cerebellar examination and deep tendon reflexes were normal. based on the opinion of the in-charge physician, anti-epileptic drugs were not prescribed at this stage. laboratory tests including complete blood cell count, liver function tests (lft), and level of blood sugar (bs), sodium, potassium, calcium, phosphorus, magnesium, urea and creatinine electrolytes were ordered. considering the full consciousness of the patient and stability of vital signs and clinical examinations, by taking safety measures and accompanied by a nurse, the patient was referred to the radiology unit to undergo a brain computed tomography (ct) scan, the results of which are shown in figure 1. what is your diagnosis? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. mohammadi 2 2. diagnosis in the patient’s ct scan, numerous calcifications were detected in the sub-cortical region, cerebellum, and basal ganglia. results of the laboratory tests of magnesium, potassium, sodium, creatinine, urea, lft, and bs were in the normal range. however, calcium = 5.9 mg/dl and phosphorus = 7.8 mg/d were reported. serum level of parathyroid hormone (pth) was measured and pth = 5.2 pg/ml was reported. considering the history of thyroid surgery and brain calcinosis in ct scan images as well as hypocalcemia, hyperphosphatemia, and low serum level of parathyroid hormone in the tests, iatrogenic hypoparathyroidism was confirmed. 3. case fate treatment started with prescription of calcium and the patient received consultation with neurology and endocrinology services. in thyroid ultrasonography, a hyperechoic nodule that measured 13×14 with coarse calcification was seen in the right lobe of the thyroid and a 15×20 nodule was found in the left lobe of the thyroid. during the hospitalization the patient did not have another seizure and was finally discharged with good general condition and hypopatathyroidism diagnosis. she underwent outpatient follow up and was also put in line for thyroidectomy surgery. 4. discussion hypoparathyroidism is an endocrine disorder that occurs due to various reasons including genetic, autoimmune, idiopathic, or iatrogenic causes (1). damage to parathyroid glands following surgery in the neck area and particularly thyroidectomy, is the most common etiology detected for this problem that despite taking all the precautious measures and proper skill of the surgeon happens temporarily in 2030% of the cases and permanently in 1-7% (2). hypoparathyroidism after thyroid surgery happens due to direct damage to the parathyroid glands or as a result of damage to its blood supplying vessels (3, 4). neuromuscular symptoms are the most common clinical manifestations of hypoparathyroidism. patients usually present with complaints of paresthesia, muscle cramps, tetany, and carpopedal spasm. however, it may also manifest as seizure, neurocognitive disorder, bronchospasm, laryngospasm, or cardiac rhythm disorders (3, 5). chronic hypocalcemia due to hypoparathyroidism caused by surgery can be subclinical for long periods of time (6). seizure and psychological disorders in this disease occur due to hypocalcemia and are reversible after correction of calcium. cognitive and extrapyramidal disorders are seen due to advanced calcification of brain tissue, usually in late diagnosis cases. manifestation of hypocalcemia symptoms in patients who undergo total thyroidectomy occurs more rapidly compared to those who undergo sub-total thyroidectomy and due to removal of more thyroid tissue and more damage to parathyroid glands, the drop in calcium is also more rapid (7). hyperphosphatemia caused by hypoparathyroidism can lead to ectopic calcification in kidney, eye, vessels, and brain in the long run (2). observation of calcinosis in brain imaging of a patient with a history of thyroidectomy should make the physician suspicious of hypoparathyroidism and guide them towards doing more evaluations (6). however, calcification of basal ganglion has numerous causes; the most common of which is calcium and phosphorus imbalance, yet some people develop this problem without an apparent cause, which is called fahr syndrome (8). initially, serum levels of calcium, phosphorus, and parathormone hormone should be measured. if hypocalcemia, hyperphosphatemia and low level of parathormone are detected, it is necessary to measure serum levels of ionized calcium and magnesium in the next step. if serum magnesium level is normal and serum level of ionized calcium is low, the diagnosis is confirmed (9). hypomagnesiumia is one of the rarest and reversible causes of hypothyroidism that has a completely different treatment compared to post-surgery hypoparathyroidism (2). the treatment for this problem in ed is prescription of calcium. for this purpose it has been recommended to use calcium gluconate and avoid injection of calcium chloride due to potentially sclerosing to veins (9). anti-epileptic drugs alone are not effective in controlling the seizure caused by electrolyte imbalances and rapid identification and correction of these imbalances, if present, is necessary for controlling seizure and preventing brain disorders (10). about 54% of the patients need anti-epileptic drugs for controlling seizure. phenytoin is epileptogenic in presence of hypocalcemia, since it induces liver enzymes and increases metabolism of vitamin d to its inactive form. therefore, it is better to use other anti-epileptic drugs in these patients if needed (5, 11). when encountering patients with seizure presenting to ed, taking accurate history and especially asking about their history of thyroid surgery can lead to clinical suspicion to hypoparathyroidism. confirming or ruling out this diagnosis can be easily and rapidly done via measuring serum levels of calcium and phosphorus. by detecting hypocalcemia and hyperphosphatemia, instead of unnecessary prescription of anti-epileptic drugs, proper treatment can be done. 5. appendix 5.1. acknowledgements we would like to express our special thanks to emergency and neurology department staff of firoozgar hospital, tehran, iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e65 5.2. conflict of interest none declared. 5.3. funding and support none declared. 5.4. authors’ contributions the authors meet the four criteria for authorship all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references 1. agarwal r, lahiri d, biswas a, mukhopadhyay j, maity p, roy m. a rare cause of seizures, parkinsonian, and cerebellar signs: brain calcinosis secondary to thyroidectomy. north american journal of medical sciences. 2014;6(10):540-2. 2. shoback dm, bilezikian jp, costa ag, dempster d, dralle h, khan aa, et al. presentation of hypoparathyroidism: etiologies and clinical features. the journal of clinical endocrinology & metabolism. 2016;101(6):2300-12. 3. kakava k, tournis s, papadakis g, karelas i, stampouloglou p, kassi e, et al. postsurgical hypoparathyroidism: a systematic review. in vivo (athens, greece). 2015;30(3):171-9. 4. zhou hy, he jc, mchenry cr. inadvertent parathyroidectomy: incidence, risk factors, and outcomes. journal of surgical research. 2016;205(1):70-5. 5. bhadada s, bhansali a, upreti v, subbiah s, khandelwal n. spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism. neurology india. 2010;59(4):586-9. 6. zisimopoulou v, siatouni a, tsoukalos g, tavernarakis a, gatzonis s. extensive bilateral intracranial calcifications: a case of iatrogenic hypoparathyroidism. case reports in medicine. 2012;2013:932184-. 7. hosseini m, otaghvar h, tizmaghz a, shabestanipour g, vahid p. evaluating the time interval for presenting the signs of hypocalcaemia after thyroidectomy. journal of clinical and diagnostic research: jcdr. 2016;10(3):pc1922. 8. rossi m, morena m, zanardi m. calcification of the basal ganglia and fahr disease. report of two clinical cases and review of the literature. recenti progressi in medicina. 1993;84(3):192-8. 9. bilezikian jp, khan a, potts jt, brandi ml, clarke bl, shoback d, et al. hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, targetâăřorgan involvement, treatment, and challenges for future research. journal of bone and mineral research. 2011;26(10):2317-37. 10. nardone r, brigo f, trinka e. acute symptomatic seizures caused by electrolyte disturbances. journal of clinical neurology (seoul, korea). 2016;12(1):21-33. 11. el otmani h, lahlou i, raji l, omari s, belmansour y, moutaouakil f, et al. striatopallidodentate calcinosis, hypoparathyroidism and neurological features: a case series study. revue neurologique. 2012;169(6-7):495-501. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com case presentation diagnosis case fate discussion appendix references archives of academic emergency medicine. 2023; 11(1): e14 or i g i n a l re s e a rc h effect of ticagrelor compared to clopidogrel on shortterm outcomes of covid-19 patients with acute coronary syndrome undergoing percutaneous coronary intervention; a randomized clinical trial reza arefizadeh1∗, seyed hossein moosavi1, sayied towfiqie1, seyed abolfazl mohsenizadeh1, mehdi pishgahi2 † 1. department of cardiology, school of medicine, aja university of medical sciences, tehran, iran. 2. department of cardiology, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: acute covid-19 infection is associated with increased adverse clinical outcomes in patients with acute coronary syndromes (acs). given that some studies suggested improved pulmonary function with ticagrelor, this clinical trial aimed to compare the effects of ticagrelor versus clopidogrel on the short-term outcomes of these patients. methods: in this multicenter clinical trial, 180 covid-19 patients with acs who underwent urgent percutaneous coronary intervention (pci) were randomized to receive ticagrelor (180mg loading dose followed by 90mg twice daily, n=90) or clopidogrel (600mg loading dose with 75mg daily, n=90), and then followed for one month after their procedure. the primary composite endpoint was a combination of all-cause mortality, myocardial infarction, and early stent thrombosis within the first month after stent implantation. results: after thirty days of follow-up, the primary composite endpoint was non-significantly lower in the ticagrelor compared to the clopidogrel group (18.5% vs 23.5% respectively, p = 0.254). based on the time-to-event analysis, the mean survival rate was 26.8 ±7.7 and 24.7 ±9.9 days, respectively, for the ticagrelor and the clopidogrel arms (log-rank p = 0.275). secondary endpoints were similar in the two trial arms, except for the mean oxygen saturation, which was higher in the ticagrelor group (95.28 ±2.68 % vs. 94.15 ± 3.55 %, respectively; p = 0.021). conclusion: among covid-19 patients with concomitant acs, who were treated with urgent pci, the composite outcome of death, myocardial infarction, and early stent thrombosis was not different between ticagrelor and clopidogrel groups. however, administration of ticagrelor was associated with a slight but statistically significant increase in oxygen saturation compared to clopidogrel, but this difference wasn’t clinically important. keywords:covid-19; myocardial infarction; percutaneous coronary intervention; ticagrelor cite this article as: arefizadeh r, moosavi sh, towfiqie s, mohsenizadeh sa, pishgahi m. effect of ticagrelor compared to clopidogrel on short-term outcomes of covid-19 patients with acute coronary syndrome undergoing percutaneous coronary intervention; a randomized clinical trial. arch acad emerg med. 2023; 11(1): e14. https://doi.org/10.22037/aaem.v11i1.1870. 1. introduction the novel coronavirus disease, known as covid-19 (coronavirus disease of 2019), is caused by the sars-cov-2 virus. it supposedly originated in wuhan, china in december 2019, ∗corresponding author: reza arefizadeh; aja university of medical sciences, etemad-zadeh st., fatemi-gharbi st., tehran, iran. email: r.arefizadeh@gmail.com, tel: +982186096356, orcid: https://orcid.org/00000002-0369-164x. † corresponding author: mehdi pishgahi; department of cardiology, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran.tel:00989123387486, email: mpishgahi.cr@gmail.com, orcid: https://orcid.org/0000-0002-1196-6535. and since then, has led to a pandemic in the whole world, with significant medical, social, economic, and political consequences for almost all countries (1). covid-19 mainly affects the lungs and leads to interstitial pneumonitis, which may be followed by respiratory distress syndrome. however, in more severe cases, it may lead to multi-organ failure and death (2). the cardiovascular system has demonstrated an important role in the disease course. while preexisting cardiovascular disease worsens the outcomes of the covid-19 infection and increases its morbidity and mortality rates, it can also result in serious cardiovascular problems by itself, such as acute coronary syndrome (acs), cardiac arrhythmia, heart failure, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. arefizadeh et al. 2 myocarditis, etc. (3, 4). among these, st-elevation myocardial infarction (stemi) is specifically important due to its high burden of adverse outcomes. according to studies in many countries, during the pandemic, different aspects of stemi, including time from symptoms to arrival at the hospital, first medical contact to wiring time, periprocedural complications, and short-term and long-term cardiovascular outcomes have changed (511). multiple studies have shown that covid-19 increases hypercoagulability in both arterial and venous systems (1215). stent thrombosis, a serious post-percutaneous coronary intervention (pci) complication with a high rate of cardiac events and mortality, is frequently reported in these studies. therefore, the selection of the p2y12 inhibitor agent (a drug that inhibits the adenosine diphosphate receptor in the platelet membrane) in such circumstances would be a crucial factor. as shown in the plato trial, in acs patients, subjects who were treated with ticagrelor, had significantly lower rates of death, myocardial infarction, and cerebrovascular events in comparison with clopidogrel, without an increased rate of major bleeding (16). these results were also demonstrated in a study of the swedeheart registry (17). furthermore, in a subgroup analysis of the plato trial, performed on the patients with pulmonary events and sepsis, the authors concluded that mortality risk after pulmonary events and sepsis in acs patients tends to be lower in the ticagrelor group compared to the clopidogrel group (18). since covid-19 mainly affects the lungs and in severe cases, leads to pulmonary-related sepsis, this interesting result encouraged us to design a randomized clinical trial to investigate the potential benefits of ticagrelor over clopidogrel, including lower rates of mortality and morbidity (myocardial infarction, stent thrombosis, hospitalization duration) and also improved pulmonary function parameters such as arterial oxygen saturation, in concomitant acs and covid-19 patients. based on this, we decided to conduct a study to compare cardiovascular outcomes, especially stent thrombosis, after pci for acs patients with concomitant covid19, between groups that took clopidogrel, versus ticagrelor as p2y12 inhibitors. 2. methods 2.1. study design and setting this randomized controlled trial was designed to compare dual antiplatelet therapy after pci in subjects who had covid-19 infection at the time, and presented to the emergency departments of artesh 501, artesh 502, and be’sat hospitals, affiliated to aja university of medical sciences, tehran, iran. subjects were randomized with a 1:1 ratio to receive either ticagrelor or clopidogrel, as their second antiplatelet drug. during the study, patients were aware of the prescribed drugs, but the physicians and investigators who analyzed the data were blinded to the trial groups and interventions. the scheme of this trial was approved by the research ethics committee of the school of medicine, aja university of medical sciences (ir.ajaums.rec.1400.233). written informed consent was obtained for participation in the study. the study protocol and design have been registered in the iranian registry of clinical trials (irct20220813055675n1). 2.2. participants subjects with the diagnosis of acs (st-elevation mi or nonst-elevation mi) who were scheduled for emergent invasive strategy treatment (coronary angiography and angioplasty), and had concurrent active covid-19 infection, were enrolled in the study. the covid-19 disease was confirmed either by a positive ct scan of the lungs, or a positive pcr test. the exclusion criteria of the participants were: 1age<18 years, 2lack of patient consent to perform coronary angiography, 3severe heart failure (left ventricular ejection fraction<30%), 4severe renal failure (glomerular filtration rate (gfr)<15), 5severe liver failure, 6history of any malignancy, chemotherapy, or radiotherapy, 7history of any intracranial or intraspinal hemorrhage, 8pregnancy or suspicion of pregnancy, 9chronic consumption of any anticoagulation drug by the patient, and 10critical covid-19 disease, which inhibits us to perform invasive treatment due to moribund condition. since this was the first trial to compare the differences between ticagrelor and clopidogrel in the setting of acs and covid-19 and specially to investigate the potential benefits of ticagrelor in acute pulmonary-induced sepsis, it was designed based on a pilot study and conducted with a sample size of 80 subjects in each group. regarding possible missing data or patient loss to follow-up, a safety margin of 10% was adopted, so eventually, a total of 176 patients (88 in each trial arm) were considered to enroll in the study. in terms of the covid-19 status, the determination of pulmonary disease severity was based on the 2022 cdc covid19 guidelines, which define severe illness as having arterial oxygen saturation < 94% on room air, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (pio2/fio2) < 300 mmhg, a respiratory rate > 30 /min, or lung infiltrate > 50%. in the absence of all of these criteria, the disease status was rated as a non-severe illness. 2.3. interventions except for the p2y12 inhibitor drug, all individuals regardless of their group received the standard guideline-directed medical treatment for acs, and the coronary interventions were done in the same way for both groups. two arms of the trial consisted of one group who were taking 180 milligrams of ticagrelor (brilavus®, abidi pharmaceutical co.) at the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e14 time of admission, followed by a daily dose of 90 milligrams every 12 hours for one year; and the other group who received 600 milligrams of clopidogrel (plavix®, abidi pharmaceutical co., licensed by sanofi) for loading dose, followed by a maintenance dose of 75 milligrams every 24 hours for one year. all the other prescription drugs and interventions were identical in both trial groups. all medications were administered in the emergency department by an expert nurse under the supervision of an emergency medicine specialist. therefore, patients were divided into their groups before the entrance to the catheterization laboratory, and the interventional cardiologist who performed pci procedures was unaware of the premedication drugs, also the person who was in charge of statistical analysis was blind to the type of drugs used. the simple randomization process was done using a random numbers table, that was generated via the research randomizer website “https://www.randomizer.org/”. 2.4. study protocol participants in placebo (n=42) and citrulline (n=40) groups received 10 gram/day microcrystalline cellulose and lcitrulline powder (karen pharma & food supplement co., iran) for 7 days, respectively. blood samples were drawn before and after the 7-day intervention. acute-phase proteins (apps) as immunology factors, complete blood count (cbc), blood urea nitrogen (bun), creatine, albumin, glycemic status, lipid profile, and liver function were determined before and after the intervention. demographic characteristics, physiological variables, and other clinical and laboratory data were collected. data on the days with mechanical ventilation were collected within 28 days. enteral feeding started for all patients within 24-48 hours of admission in hospital. all subjects received the same hospital prepared enteral formulation (hpf), which contained 42.8% carbohydrates, 16.6% protein, and 34.2% fat. 2.5. outcomes the primary efficacy endpoint was the composite of allcause mortality, the occurrence of myocardial infarction, or stent thrombosis during the index hospitalization or followup period (one month). the secondary efficacy endpoints were death from any cause alone, the occurrence of myocardial infarction alone, acute or subacute stent thrombosis (defined as occurring 0-24 hours and within 30 days after pci, respectively), the duration of the patient’s hospitalization, the mean of arterial oxygen saturation during the main admission, the “neutrophil-to-lymphocyte ratio” (nlr) and the “platelet-to-lymphocyte ratio” (plr), two indices that are considered to be related with covid-19 infection severity. subjects were followed for one month after their hospital admission. 2.6. blinding in this clinical trial, blinding was applied on two levels: the researchers and the data analyzer. the researchers included an interventional cardiologist who performed pci procedures and a general cardiologist who was in charge of the randomization process and assigned participants to the interventions. the patients were aware of the types of drugs that were prescribed because they used them at least for one year on a daily basis. the data processor was blind to the type of drug administered for each trial arm. 2.7. statistical analysis the statistical analysis was done based on the intention-totreat method and applied to all the subjects who were initially randomized, but also, performed a per-protocol analysis, which had the same findingss, because of the small number of total missed subjects. the kolmogorov-smirnov test was used to evaluate the distribution of the continuous numerical variables. the normally distributed variables were reported as the mean and standard deviation and nonnormal variables as the median with 25th, and 75th quartiles. to examine the difference of continuous variables between the two groups, the student’s t-test, and the non-parametric two independent samples test were used, respectively, for the normal and the skew-distributed variables. qualitative variables were reported as frequencies in their related group, and the chi-square or fisher’s exact tests were performed to analyze their inter-group differences. the mann-whitney u test was applied to compare the primary composite endpoint between two trial arms. the time to death was reported using the kaplan-meier method and the difference was evaluated via the log-rank test. all of the statistical analyses were performed with the ibm spss statistics software for windows, version 26. the significance level was determined at a p-value<0.05. 3. results 3.1. trial population a total of 256 patients were considered to enroll in this study, from june 2022 to september 2022, of whom 76 individuals had the exclusion criteria, and finally, 180 patients were assigned to randomized trial groups (figure 1). during followup, ten subjects were excluded from the study due to loss to follow (one in the clopidogrel group and nine in the ticagrelor group). the baseline and procedural characteristics of the patients are shown in table 1. the mean age of the participants was 59.4±12.5 and 60.9±12.4 years in the clopidogrel and ticagrelor groups, respectively. there was a male predominance in both groups, with 73% of patients in the clopidogrel and 79% of people in the ticagrelor group being this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. arefizadeh et al. 4 table 1: baseline characteristics of the total population age (years) 59.4 ± 12.5 60.9 ± 12.4 0.460 gender male 65 (73.0) 64 (79.0) 0.363 bmi (kg/m2 ) 28.6 ± 4.9 27.6 ± 4.3 0.179 ejection fraction (%) 37.4 ±5.9 39.0 ± 6.5 0.158 covid-19 status non-severe disease 68 (76.4) 62 (76.5) 0.983 severe disease 21 (23.6) 19 (23.5) cardiovascular risk factor diabetes 40 (44.9) 46 (56.8) 0.123 hypertension 44 (49.4) 37 (45.7) 0.624 dyslipidemia 45 (50.6) 41 (50.5) 0.994 family history 43 (48.3) 45 (55.6) 0.345 cigarette smoker 33 (37.1) 31 (38.3) 0.873 opium addiction 13 (14.6) 18 (22.2) 0.199 laboratory tests triglyceride (mg/dl) 129.2 ± 73.4 151.4 ± 104.2 0.132 total cholesterol (mg/dl) 155.6 ± 43.0 158.5 ± 45.3 0.668 hdl cholesterol (mg/dl) 40.1 ± 10.4 40.4 ± 9.4 0.873 ldl cholesterol (mg/dl) 96.8 ± 34.0 97.0 ± 35.0 0.960 fasting bs (mg/dl) 141.1 ± 77.8 155.6 ± 73.6 0.190 creatinine (mg/dl) 1.2 ± 0.7 1.1 ± 0.2 0.519 hemoglobin (g/dl) 14.70 ± 2.0 14.75 ± 1.8 0.849 white blood cells (*106 /l) 11937.6 ± 3487.3 10941.1 ± 3503.2 0.065 lymphocyte (%) 21.7 ± 11.5 23.1 ± 12.7 0.555 platelet (*106 /l) 247321.3 ± 61704.3 234839.5 ± 65281.4 0.116 physical examination systolic bp (mmhg) 135.4 ± 27.9 138.2 ± 25.9 0.505 diastolic bp (mmhg) 86.0 ± 16.9 88.1 ± 18.8 0.447 heart rate (beat/min) 83.8 ± 16.5 86.7 ± 18.2 0.398 procedural properties stent length (mm) 32.8 ± 9.9 30.4 ± 8.8 0.304 iib/iiia inhibitors 58 (65.2) 44 (54.3) 0.149 slow flow cad 25 (28.1) 18 (22.2) 0.379 thrombo-suction 10 (11.2) 6 (7.4) 0.393 baseline timi 0 60 (67.4) 54 (66.7) 1 1 (1.1) 2 (2.5) 0.312 2 10 (11.2) 15 (18.5) 3 18 (20.2) 10 (12.3) final timi 0 1 (1.1) 1 (1.2) 1 2 (2.2) 4 (4.9) 0.713 2 22 (24.7) 16 (19.8) 3 64 (71.9) 60 (74.1) blush grade 0 6 (6.7) 8 (9.9) 1 18 (20.2) 14 (17.3) 0.873 2 31 (34.8) 28 (34.6) 3 34 (38.2) 31 (38.3) thrombus burden 0 9 (10.1) 4 (4.9) 1 13 (14.6) 13 (16.0) 2 14 (15.7) 21 (25.9) 0.502 3 26 (29.2) 22 (27.2) 4 4 (4.5) 2 (2.5) 5 23 (25.8) 19 (23.5) data are presented as mean ± standard deviation or frequency (%). bmi: body mass index; hdl: high-density lipoprotein; ldl: low-density lipoprotein; bs: blood sugar; bp: blood pressure; cad: coronary artery disease; timi: thrombolysis in myocardial infarction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e14 table 2: rates of the primary and secondary endpoints during follow-up outcomes clopidogrel (n=89) ticagrelor (n=81) p-value primary composite endpoint* frequency (%) 23 (25.8) 15 (18.5) 0.254 secondary endpoints all-cause mortality 21 (23.6) 14 (17.3) 0.309 myocardial infarction 3 (3.4) 1 (1.2) 0.359 stent thrombosis 3 (3.4) 1 (1.2) 0.359 hospitalization duration (days) 4.84 ± 2.34 4.30 ± 2.08 0.161 oxygen saturation (%) 94.15 ± 3.55 95.28 ± 2.68 0.021 nlr 4.98 ± 4.31 4.54 ± 3.65 0.585 plr 133.02 ± 91.4 135.70 ± 97.16 0.904 data are presented as mean ± standard deviation or frequency (%). *: all-cause mortality, myocardial infarction, or stent thrombosis; nlr: neutrophil to lymphocyte ratio; plr: platelet to lymphocyte ratio. male. about 76.5% of all subjects in both groups were at the non-severe stage of covid-19 disease at the time of randomization. as illustrated in table 1, there was no statistical difference between trial arms in any of the characteristics. 3.2. primary endpoint as seen in table 2, at 30 days of follow-up, the primary endpoint (composite of all-cause mortality, myocardial infarction, or stent thrombosis) occurred in 24 (25.8%) subjects in the clopidogrel arm, compared to 15 (18.5%) cases in the ticagrelor arm (p = 0.254). furthermore, the mean survival rate during the first month after the patient’s admission was 24.7 (95% ci=22.6, 26.7) and 26.8 (95% ci= 25.1, 28.5) days, respectively, for the clopidogrel and the ticagrelor groups (figure 2; p = 0.275). 3.3. secondary endpoints according to table 2, all-cause mortality occurred more frequently in the clopidogrel arm than in the ticagrelor arm (23.6% versus 17.3%, p=0.309). moreover, the occurrence of myocardial infarction was lower in the ticagrelor group (1.2% versus 3.4%, p=0.359). since all myocardial infarctions in both trial arms were due to stent thrombosis, the results for stent thrombosis were the same as the results of myocardial infarction. yet, all these inter-group differences were not statistically significant. this also applies to the other secondary endpoints including the duration of hospitalization (p=0.161), the nlr (p=0.585), and the plr (p=0.904) indices. however, the arterial oxygen saturation differed, as patients in the ticagrelor group had a statistically significant higher mean oxygen saturation during their hospitalization compared to the clopidogrel group, nevertheless, the difference wasn’t clinically remarkable (95.28 ± 2.68 % versus 94.15 ± 3.55 %, respectively, p=0.021). 4. discussion in this randomized clinical trial, we found that in patients who presented with acs and had been treated with pci, while concomitantly having active covid-19 infection, ticagrelor was associated with statistically non-significant lower rates of combined all-cause mortality, myocardial infarction, and stent thrombosis one month after the procedure. however, despite individuals in the ticagrelor group having statistically significant higher mean arterial oxygen saturation during the index hospitalization, this difference was not clinically important. many reports indicate early (within the first month), late (30 days to one year), and very late (beyond the first year) stent thrombosis after pci in patients with concomitant covid-19 disease (15, 19-27). a study by hamadeh et al. showed that early stent thrombosis occurred in 21% (5 out of 24) of stemi patients who were treated with primary pci (28). hypothetically, the higher incidence of thrombotic events during systemic viral inflammatory states may be related to hypercoagulability mechanisms such as immunemediated thrombotic conditions, macrophage activation, complement activation, anti-phospholipid syndrome, and dysregulation of the renin-angiotensin-aldosterone system (13). however, stent thrombosis could lead to an increased rate of morbidity and mortality. in our study, one of the three patients who had early stent thrombosis in the clopidogrel arm died due to unsuccessful revascularization and following persistent cardiogenic shock; the two other patients and one subject with stent thrombosis in the ticagrelor group underwent successful urgent coronary angioplasty and survived. even though ticagrelor decreased early stent thrombosis in our study, it was not statistically significant, maybe due to the small number of events. covid-19 patients experience flu-like symptoms such as fever, fatigue, and cough. as the disease progresses, shortness of breath, dyspnea, and in severe cases, decreased arterial oxygen saturation, lymphopenia, and ground glass opacthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. arefizadeh et al. 6 figure 1: consort flowchart of enrollment, randomization, and follow-up of the patients. ities in chest ct scans may occur, eventually leading to acute respiratory distress syndrome (ards) (29). an important aim of this trial was to investigate if ticagrelor could improve pulmonary function in our patients or not. in a study by storey et al. on the results of the previous large plato clinical trial, they compared the incidence of pulmonary adverse events or mortality in 18,421 patients with acs, between two groups of ticagrelor and clopidogrel. the adverse events in the ticagrelor group occurred less than in the clopidogrel group (275 versus 331; p= 0.019), also deaths were significantly fewer in ticagrelor than in clopidogrel group (33 versus 71; p<0.001). eventually, they concluded that the mortality related to pulmonary adverse events in patients with acs decreases when the patients were on ticagrelor compared to clopidogrel treatment (18). sexton and colleagues developed a study to investigate whether ticagrelor has possible beneficial effects on pneumonia patients. finally, they showed that ticagrelor improved pulmonary function during pneumothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e14 figure 2: kaplan-meier curve comparing survival rates between the two trial arms during follow-up. sepsis compared to placebo (free from supplemental oxygenation period: or=1.08; 95% ci= 1.01 to 1.15) (30). they also realized that ticagrelor administration in patients with pneumonia and sepsis lowered platelet-leukocyte aggregation and reduced interleukin-6 levels, which are associated with an anti-inflammatory effect. as mentioned before, in our clinical trial, we found that individuals in the ticagrelor arm had significantly higher mean oxygen saturation in comparison with those in the clopidogrel arm. (95.26±2.68% versus 94.29±3.55%, p=0.028). xie et al. studied the association between hypoxemia and covid-19 mortality. they found that hypoxemia is independently related to higher inhospital mortality, and an oxygen saturation cut-off value of 90.5%, had 84.6% sensitivity and 97.2% specificity in the prediction of survival (31). thus, our findings could lead to conducting further studies that survey the potential beneficial effects of ticagrelor on covid-19 patients to decrease overall mortality. solano-lópez et al., demonstrated that in patients with acute stemi, all-cause mortality, and cardiovascular mortality are remarkably increased when the concomitant covid-19 infection is present, compared to covid-19-negative individuals (25% versus 3.8% (p < 0.001), and 15.2% versus 1.8% (p = 0.001), respectively) (32). in the study by mohsenizadeh et al., the presence of covid-19 in patients undergoing primary pci was associated with significantly higher duration of hospitalization and in-hospital mortality (33, 34). in our study, the overall 30-day mortality in the total population was 20.58% (35 out of 170), while people in the ticagrelor group died less than those in the clopidogrel group, the difference was not statistically significant. furthermore, the overall period of hospitalization was not different between the two trial arms. 5. limitations although this study was designed based on a clinical trial, some limitations should be considered when interpreting the results. since this was the first trial that compared the therapeutic effects of ticagrelor on covid-19 outcomes in acs patients, the total sample size and follow-up duration were limited. a study with a larger sample size and a longer followup duration might be more confidently conclusive. to the best of our knowledge, this was the first trial develthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index r. arefizadeh et al. 8 oped to investigate the beneficial effects of ticagrelor compared to clopidogrel, in patients with concomitant acs and covid-19 infection who had undergone urgent coronary angioplasty. as previously said, we assessed the early (acute and subacute) stent thrombosis, while it’s shown that covid-19 could be associated with late (within the first year after pci) and even very late (beyond the first year) stent thrombosis, so future studies should be designed with longer follow-up duration and include more subjects so it would be possible that the non-significant results from this study become statistically significant and indicate the administration of ticagrelor in such patients with more emphasis. 6. conclusions we found that in patients who presented with acute coronary syndromes and active covid-19, who were treated with urgent coronary angioplasty, ticagrelor in comparison with clopidogrel did not significantly decrease all-cause mortality, myocardial infarction, or early stent thrombosis in 30day follow-up. although ticagrelor administration was associated with a statistically significant higher mean arterial oxygen saturation during admission, but this difference was not clinically remarkable. however, this finding might be indicative of ticagrelor’s potential benefits for improving pulmonary function in such patients. 7. declarations 7.1. acknowledgments the authors would like to acknowledge the staff of “artesh 501”, “artesh 502”, “golestan” and “be’sat” hospitals in tehran, iran. 7.2. conflict of interest the authors declare no potential conflict of interest regarding this manuscript’s study design, writing, or publication. 7.3. fundings and supports this trial was supported by aja university of medical sciences. the funding source did not play any role in the collection of data or analysis and interpretation of the results, nor the design of the study or publication of the article. 7.4. authors’ contribution reza arefizadeh: the concept and design of the clinical trial, and patient allocation. seyed hossein moosavi: the patient allocation and supervising of the team. sayiied tufeeqee: patient follow-up and writing the manuscript. seyed abolfazl mohsenizadeh: statistical analysis and writing the manuscript. mehdi pishgahi: trial design and analysis of the results. all authors read and approved final version of manuscript. references 1. zhou p, yang x-l, wang x-g, hu b, zhang l, zhang w, et al. a pneumonia outbreak associated with a new coronavirus of probable bat origin. nature. 2020;579(7798):270-3. 2. guzik tj, mohiddin sa, dimarco a, patel v, savvatis k, marelli-berg fm, et al. covid-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. cardiovasc res. 2020;116(10):166687. 3. driggin e, madhavan mv, bikdeli b, chuich t, laracy j, biondi-zoccai g, et al. cardiovascular considerations for patients, health care workers, and health systems during the covid-19 pandemic. j am coll cardiol. 2020;75(18):2352-71. 4. bansal m. cardiovascular disease and covid-19. diabetes & metabolic syndrome: clinical research & reviews. 2020;14(3):247-50. 5. tomasoni d, adamo m, italia l, branca l, chizzola g, fiorina c, et al. impact of covid-2019 outbreak on prevalence, clinical presentation and outcomes of st-elevation myocardial infarction. j cardiovasc med. 2020;21(11):874-81. 6. wu j, mamas ma, mohamed mo, kwok cs, roebuck c, humberstone b, et al. place and causes of acute cardiovascular mortality during the covid-19 pandemic. heart. 2021;107(2):113-9. 7. jain v, gupta k, bhatia k, bansal a, arora s, khandelwal ak, et al. management of stemi during the covid-19 pandemic: lessons learned in 2020 to prepare for 2021. trends cardiovasc med. 2021;31(3):135-40. 8. chew nw, sia c-h, wee h-l, jia-da benedict l, rastogi s, kojodjojo p, et al. impact of the covid-19 pandemic on door-to-balloon time for primary percutaneous coronary intervention—results from the singapore western stemi network—. circ j. 2021;85(2):139-49. 9. de luca g, cercek m, jensen lo, vavlukis m, calmac l, johnson t, et al. impact of covid-19 pandemic and diabetes on mechanical reperfusion in patients with stemi: insights from the isacs stemi covid 19 registry. cardiovasc diabetol. 2020;19(1):215. 10. rodriguez-leor o, cid-álvarez b, ojeda s, martínmoreiras j, rumoroso jr, lópez-palop r, et al. impact of the covid-19 pandemic on interventional cardiology activity in spain. rec interv cardiol. 2020;2(2):82-9. 11. scholz kh, lengenfelder b, thilo c, jeron a, stefanow s, janssens u, et al. impact of covid-19 outbreak this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e14 on regional stemi care in germany. clin res cardiol. 2020;109(12):1511-21. 12. choudhary r, kaushik a, sharma jb. covid-19 pandemic and stent thrombosis in a post percutaneous coronary intervention patient-a case report highlighting the selection of p2y12 inhibitor. cardiovascular diagnosis and therapy. 2020;10(4):898. 13. hanff tc, mohareb am, giri j, cohen jb, chirinos ja. thrombosis in covid-19. am j hematol. 2020;95(12):1578-89. 14. miesbach w, makris m. covid-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. clin appl thromb hemost. 2020;26:1076029620938149. 15. prieto-lobato a, ramos-martínez r, vallejo-calcerrada n, corbí-pascual m, córdoba-soriano jg. a case series of stent thrombosis during the covid-19 pandemic. case reports. 2020;2(9):1291-6. 16. wallentin l, becker rc, budaj a, cannon cp, emanuelsson h, held c, et al. ticagrelor versus clopidogrel in patients with acute coronary syndromes. n engl j med. 2009;361(11):1045-57. 17. sahlén a, varenhorst c, lagerqvist b, renlund h, omerovic e, erlinge d, et al. outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from swedeheart registry. eur heart j. 2016;37(44):3335-42. 18. storey rf, james sk, siegbahn a, varenhorst c, held c, ycas j, et al. lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the plato study. platelets. 2014;25(7):51725. 19. skorupski wj, grygier m, lesiak m, kałużna-oleksy m. coronary stent thrombosis in covid-19 patients: a systematic review of cases reported worldwide. viruses. 2022;14(2):260. 20. hinterseer m, zens m, wimmer rj, delladio s, lederle s, kupatt c, et al. acute myocardial infarction due to coronary stent thrombosis in a symptomatic covid-19 patient. clin res cardiol. 2021;110(2):302-6. 21. kunal s, pathak v, pathak k, mishra m, sharma sm, bhandari s. very late stent thrombosis associated with covid19 infection: a case report and review of the literature. monaldi archives for chest disease. 2022;92(2):1960. 22. ayan m, kovelamudi s, al-hawwas m, editors. subacute stent thrombosis in a patient with covid-19 pneumonia. baylor university medical center proceedings; 2021;34(1):175-177. taylor & francis. 23. kermani-alghoraishi m. a review of coronary artery thrombosis: a new challenging finding in covid-19 patients and st-elevation myocardial infarction. curr probl cardiol. 2021;46(3):100744. 24. elkholy ko, khizar a, khan a, hakobyan n, sahni s. subacute stent thrombosis in a patient with covid-19 despite adherence to antiplatelets. cureus. 2021;13(2): e13194. 25. antuña p, rivero f, del val d, cuesta j, alfonso f. late coronary stent thrombosis in a patient with coronavirus disease 2019. jama cardiology. 2020;5(10):1195-8. 26. galeazzi gl, loffi m, di tano g, danzi gb. severe covid-19 pneumonia and very late stent thrombosis: a trigger or innocent bystander? korean circulation journal. 2020;50(7):632. 27. montaseri m, golchin vafa r, attar a, ali hosseini s, kojuri j. stent thrombosis during covid-19 pandemic: a case series. clinical case reports. 2022;10(5):e05872. 28. hamadeh a, aldujeli a, briedis k, tecson km, sanzsánchez j, al-obeidi a, et al. characteristics and outcomes in patients presenting with covid-19 and stsegment elevation myocardial infarction. the american journal of cardiology. 2020;131:1-6. 29. batah ss, fabro at. pulmonary pathology of ards in covid-19: a pathological review for clinicians. respir med. 2021;176:106239. 30. sexton tr, zhang g, macaulay te, callahan la, charnigo r, vsevolozhskaya oa, et al. ticagrelor reduces thromboinflammatory markers in patients with pneumonia. jacc: basic to translational science. 2018;3(4):435-49. 31. xie j, covassin n, fan z, singh p, gao w, li g, et al., editors. association between hypoxemia and mortality in patients with covid-19. mayo clin proc; 2020:95(6): 1138-1147 elsevier. 32. solano-lópez j, zamorano jl, sanz ap, amat-santos i, sarnago f, ibañes eg, et al. risk factors for in-hospital mortality in patients with acute myocardial infarction during the covid-19 outbreak. revista española de cardiología (english edition). 2020;73(12):985-93. 33. mohsenizadeh sa, alidoosti m, jalali a, tofighi s, salarifar m, poorhosseini h, et al. comparison of angiographic and clinical outcomes after primary percutaneous coronary intervention for st-elevation myocardial infarction between patients with and without concomitant covid-19 infection. crit pathw cardiol. 2022;21(3):141-6. 34. namazi mh, saemifard f, pishgahi m. one-month outcomes of cases receiving ticagrelor after percutaneous coronary intervention; a case series. arch acad emerg med [internet]. 2020;8(1):e42. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusions declarations references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 50 emergency (2014); 2 (1): 50-52 photo quiz a 16-year-old girl with acute onset respiratory distress saeed safari1, ebrahim karimi2, alireza baratloo1, mostafa alavi-moghaddam3, mohammad kalantarimeibodi4* 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, besat hospital, aja university of medical sciences, tehran, iran 3. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 4. trauma research center, shiraz university of medical sciences, shiraz, iran figure1: lateral neck x-ray.  figure2: posterior anterior upright chest x-ray.  cite this article as: safari s, karimi e, baratloo a, alavimoghadam m, kalantarimeibodi m. a 16-year-old girl with acute onset respiratory distress. 2014;2(1): 50-2. case presentation:1 16-year-old girl with an intellectual disability (known case of down syndrome) arrived in the emergency department with complaints of severe breathlessness, bloody salivation (bright red blood or clots), and difficulty in speaking and swallowing of liquids and solids. the patient gradually developed progressive bloody salivation and hoarseness, never had any history of trauma to the head and neck and respiratory problems, and was symptomatic from the previous 48 h. furthermore, the patient had a positive history of peptic ulcer, chronic consumption of non-steroidal antiinflammatory drugs, and traveled out of town and drank water from a well in the mentioned period. on admission, the patient had a respiratory rate of *corresponding author: mohammad kalantarimeibodi; department of emergency medicine, namazi hospital, namazi square, zand avenue, shiraz, iran. mobile phone: +989151132998; phone/fax: +982122721155. email: kalantari_meibodi@yahoo.com received: 22 december 2013; accepted: 20 january 2014 17 per min, pulse rate of 89 per min, blood pressure of 120/80 mmhg, 90% o2 saturation in room air, and 38°c axillary temperature. the only positive finding on physical examination was inspiratory stridor. the auscultation of lung and heart sounds was normal. digital rectal examination revealed brown feces. throat examination was not possible owing to lack of patient cooperation. after initial assessment and essential consideration, electrocardiography (ecg) and imaging was performed. the ecg showed normal sinus rhythm, and analysis of arterial blood gas revealed the following: ph = 7. 35, pa-co2 = 39 mmhg, hco3 = 24 meq/l, pao2 = 89 mmhg, and o2 saturation = 92%. all other laboratory data, including complete blood counts (cbc), urine analysis, hepatic and renal function tests, and coagulation profile were in the normal range. figure 1 and 2 show the lateral neck and chest x-ray of the patient, respectively. what is your diagnosis? a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 51 emergency (2014); 2 (1): 50-52 diagnosis: live foreign body in oropharynx case fate: based on history and presentation, a foreign body in the oropharynx was suspected, and hence, a lateral neck x-ray was taken (figure 1). imaging revealed an occupant mass in the oropharynx (figure 3, dash triangle). owing to the progress of the patient’s respiratory problem, direct laryngoscopy was performed under mild sedation and local anesthesia (recurrent laryngeal nerve block with 1% lidocaine). a massive brown-reddish mobile mass was observed protruding in the oropharynx, which was found to be a live leech that ingested blood. after injection of 3 ml of 2% lidocaine of the mobile mass, suctioning was performed and the foreign body was removed. the patient was asymptomatic after regaining complete baseline consciousness. discussion: for the diagnosis of patients with respiratory distress, perfect and detailed history taking and systematic examination followed by relevant investigations are the key points. respiratory distress is an emergency condition that requires immediate attention, because an ensuing airway obstruction may cause hypoxia and death. foreign body, rarely the live ones, should be included as a differential diagnosis of these patients. the patients can present with acute onset respiratory distress, hoarseness, hemoptysis, and suffocation sensation, and even oral bleeding and dysphagia. the diagnosis of live foreign body as a cause of respiratory distress should be considered in areas where drinking of water from pond, pit, and river is common (1-5). among these scarce entities, leeches are one of the well-known ones. these parasites attach themselves to the vertebrate hosts and suck out the blood (4, 6). a medical center in pakistan, in a period of 10 years, had reported 28 treated cases of foreign body infestation with leeches. in all of these cases, the complaints included recurrent episodes of epistaxis, blood-spitting, dysphagia, dyspnea, odynophagia, and hemoptysis, several days before admission. examination of the cases showed blood-engorged leech in green-brown mass protruding from different nasopharyngeal or oropharyngeal areas (7). leeches generally live in streams and puddles. hence, drinking of contaminated water could lead to infestation of leech anywhere in the gastrointestinal and upper respiratory tract, resulting in various presentations. when a leech is settled in the nasal cavity or nasopharynx, the patients may present with complaints of epistaxis and nasal fullness or even sensation of a mobile foreign body in the nasal cavity. in contrast, attachment of leech to the oral cavity could result in the patients spitting blood and feeling the presence of a foreign body, whereas attachment to the larynx could lead to airway obstruction and voice change (8, 9). because of dispersed data, there are still considerable controversies over the most suitable treatment option. however, direct laryngoscopy under general anesthesia is necessary for both diagnosis and removal of the leech. some studies have reported that rapid and careful surgical intervention by applying a forcep to the middle of the leech's body and providing a quick pull under local anesthesia is a successful treatment procedure in adults, and that bleeding in the attached site immediately stops after removal of the leech (7, 8). conclusion: with the available sporadic reported cases of leech as a live foreign body from around the world, it appears that the sudden onset of respiratory symptoms along with a history of possible drinking of contaminated water are the most helpful clues for consideration of this diagnosis. future studies on treatment of this condition are necessary to develop a globally acceptable approach. figure3: lateral neck x ray. the location of foreign body is marked with dash triangle.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 52 safari et al acknowledgment: we would like to express our special thanks to the emergency department staffs. conflict of interest: there was no conflict of interest. author’s contribution: all the authors have contributed to drafting/ revising the manuscript, study concept, or design, as well as data interpretation. references: 1. yazc h, dogan s, sunter av, ylmaz e, daskaya h. surprising cause of respiratory distress in child: laryngeal leech. j craniofac surg. 2012;23(3):e272-e3. 2. rahimi-rad m, alizadeh e, samarei r. aquatic leech as a rare cause of respiratory distress and hemoptysis. pneumologia. 2011;60(2):85-8. 3. al-hadrani a, debry c, faucon f, fingerhut a. hoarseness due to leech ingestion. j lar otol. 2000;114 (2):1456. 4. uygur k, yasan h, yavuz l, dogru h. removal of a laryngeal leech: a safe and effective method. am j otolaryngol. 2003;24(5):338-40. 5. kuehnemund m, bootz f. rare living hypopharyngeal foreign body. head neck. 2006;28(11):1046-8. 6. saki n, rahim f, nikaghlagh s, saki g. meta analysis of the leech as a live foreign body: detection, precaution and treatment. pak j biol sci. 2009;12(24):1556-63. 7. guerrant rl, walker dh, weller pf. tropical infectious diseases: principles, pathogens and practice. 2nd ed: saunders; 2011. p. 1341. 8. kaygusuz i, yalçin ş, keleş e. leeches in the larynx. eur arch otorhinolaryngol. 2001;258(9):455-7. 9. kumar s, kishore k, sharma m. live leech in the larynx. indian j med special. 2013;4(2): 315-6. archives of academic emergency medicine. 2022; 10(1): e82 rev i ew art i c l e point-of-care tests’ role in time metrics of urgent interventions in emergency department; a systematic review of literature sara rahsepar1, mohammad sadegh sanie jahromi2, samaneh abiri2, reza akhavan3, hossein akhavan4, bita abbasi5, fatemeh maleki6, somayyeh ahmadnezhad7, behrang rezvani kakhki3, navid kalani8∗, pourya adibi9 † 1. department of dermatology, mashhad university of medical sciences, mashhad, iran. 2. research center for non-communicable diseases, jahrom university of medical sciences, jahrom, iran. 3. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 4. department of pediatrics, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 5. department of radiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 6. department of emergency medicine, school of medicine, birjand university of medical sciences, birjand, iran. 7. department of emergency medicine, ramsar campus, mazandaran university of medical sciences, ramsar, iran. 8. research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. 9. anesthesiology, critical care and pain management research center, hormozgan university of medical sciences, bandar abbas, iran. received: july 2022; accepted: august 2022; published online: 10 october 2022 abstract: introduction: point-of-care testing (poct) could be helpful in clinical decisions, treatment selection, monitoring, prognostication, operational decision-making, and resource utilization. this study aimed to review the role of poct in time metrics of performing urgent interventions in the emergency department (ed) or disposition time to proper care. methods: this was a systematic review of the literature based on the prisma statement. pubmed, scopus, web of science, and embase databases were searched for studies reporting the application of the poct in the ed with outcomes of the time to intervention or disposition. results: after reviewing 3708 articles, 16 studies with 100,224 participants were included in this systematic review. there were 5 randomized clinical trials (rcts), 5 retrospective cohorts, 2 prospective cohorts, and 4 before-after studies. all studies were performed in an ed setting except for one study of prehospital ems air medical transport. different panels, ultrasound, cardiac parameters, echocardiography, and polymerase chain reaction (pcr) pocts were used in the studies. regarding the outcome measures, studies with many types of patients referring to ed used different indices of time to intervention or time to disposition. studies on different shock circumstances used the time to the first bolus of hydration or vasopressor or intravenous antibiotics for septic shock patients and central venous catheterization (cvc) placement time in one study. time to imaging was considered as the outcome in some studies. overall, there was a high risk of bias, especially in case of the randomization methods, and non-blinded designs in rcts. there was lower possibility of bias in non-randomized studies but the studies did not have enough follow-ups and in case of studies using advanced panels of poct, results do not seem to be easily applicable to public health care in many countries. conclusion: in synthesis of the evidence, all included studies were reporting the benefits of the poct in decreasing the time to proper interventions and increasing the time to negative interventions in the last lines of critical care as well as the intubation and cvc placement. keywords: emergency medicine; point-of-care systems; point-of-care testing; emergency treatment cite this article as: rahsepar s, sanie jahromi ms, abiri s, akhavan r, akhavan h, abbasi b, et al. point-of-care tests’ role in time metrics of urgent interventions in emergency department; a systematic review of literature. arch acad emerg med. 2022; 10(1): e82. https://doi.org/10.22037/aaem.v10i1.1817. ∗corresponding author: navid kalani; research center for social determinants of health, jahrom university of medical sciences, jahrom, iran. email: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. rahsepar et al. 2 1. introduction traditional public health systems are suffering from limited, delayed, and inefficient medical services, especially when confronted with crowdedness, disasters, and the aging population (1). in the face of ever-increasing public demand, emergency departments (eds) face many challenges in maintaining consistent quality care (2, 3). improved survival of critically ill patients in the emergency department is directly related to advances in early identification and treatment (4). frequent overcrowding and extended waiting times strain emergency departments’ capacity and compromise patient care. until a few decades ago, the patient or his/her sample had to be sent to the laboratory, and it took hours or days for the results to reach the physician, and during this time, the patient’s care had to continue without the information needed by the physician (5). bedside tests are simple medical diagnostic tests that can be performed at the time and place of patient care. their simplicity is due to the advancement in technology. in recent decades, more and more trials have been performed on point-of-care testing (poct). poct enables faster clinical decisions during diagnosis, treatment selection and monitoring, prognostication and operational decision-making, and resource utilization (6, 7). poct has been shown to decrease the time to thrombolysis in stroke by as much as half an hour (8). also, as its aim of creation was, poct improves test turnaround times in emergency departments (9). therefore, with regard to all of the above, the role of poct can be considered to help cope with the stress of overcrowding of ed (10). while many review studies have been conducted on the efficacy of different commercially available pocts in case of diagnostic accuracy of different medical conditions (11-13), and logically it should provide faster results and better test turnaround times, no previous study has evaluated its final effects on the time-critical patients of emergency department. alter et al. evaluated the effect of applying poct on the destination of the ed patients and drew a conclusion that these devices decreased the total length of hospital stay (14). but no inhospital timing studies are provided in the literature. so, the aim of this study was to review the role of poct in time metrics for performing urgent interventions in the ed or disposition time to proper care. navidkalani@ymail.com, orcid: https://orcid.org/0000-0003-1900-4215. † corresponding author: pourya adibi; anesthesiology, critical care and pain management research center, hormozgan university of medical sciences, bandar abbas, iran. email: adibip@hums.ac.ir , orcid: https://orcid.org/0000-0003-2296-2166. 2. methods 2.1. study design and setting the present study is a systematic review that was carried out in accordance with the items mentioned in the preferred reporting items for systematic reviews and meta-analyses (prisma) (15). a pico model was used to structure the study question. population of interest was patients referring to ed. patients referring to ed are classified based on various triage models to address the urgency of the medical condition in literature. siegfried et al. classified patients of ed into 3 groups; simple, complex, and critical (16). simple group would receive only simple care and point-of-care tests along with only oral medications. complex patients would undergo laboratory and imaging studies, receive intravenous medications, and remain under observation in ed or be admitted to a ward. critical patients would be admitted to intensive care unit (icu) from the ed and receive resuscitative care in ed, urgent cardiac interventions, gastrointestinal bleeding care, and other urgent surgeries or invasive diagnostic studies. intervention/exposure of interest was poct application in ed. comparison was done with the main standard of care test. outcome was considered as time to critical care intervention. critical care intervention included admission to icu, cardiac interventions, urgent gastrointestinal (gi) interventions, and urgent surgeries. 2.2. search strategy a systematic electronic search in pubmed, scopus, web of science and embase databases using the keywords "emergency medicine", "point of care", " "point of care testing", "poct", "rapid testing", "bedside testing", "emergency care" and all selected pocts was done. a detailed search strategy of “((emergency medicine) or (ems) or (emergency care) or (emergency department) or (emergency room) or (ed) or (pre-hospital) ) and ((point of care testing) or (poct) or (bedside testing) or (lactate poct) or (rapid testing))” was conducted in pubmed. if there was a systematic review about poct in the emergency setting, that study was also included in our review and the years after the search conducted in the included study were searched. this was used when the review focused on a single poct item. the main text of the articles was also evaluated for additional references. in case of need for further data, contact with study authors to identify additional data was planned, which was not performed/needed. all searches were conducted from inception to august 2022. 2.3. eligibility criteria all observational or interventional clinical studies that were done in the emergency room and pre-hospital research envithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e82 ronment were included in the study, when applying pocts in the treatment process of time-critical diseases. only studies on non-trauma patients were considered, as the classification of the severity of the trauma cannot be merged with classifications of nontraumatic referrals of the ed due to the different pathways of management. applying the abcd rule in traumatic patients, most time-critical interventions should be performed in seconds to minutes; in addition, the airway management and laboratory data are less diagnostic and are mostly used for disease severity evaluation. studies were limited to adult populations to increase the homogeneity between studies to be able to synthesize the results. studies conducted in various other departments in the hospital and at home or outside the hospital (except ems) were not included in the study. gray literature studies were not included as results that are not peer-reviewed might bias the final findings. studies written in a language other than english were also excluded. studies reporting accuracy and time to results of the test were not sought in this study as we were planning to evaluate the role of poct in decreasing the test turnaround times. 2.4. data collection after removing the duplicates, the remaining studies were independently reviewed by two reviewers for eligibility to be included in the study. any disagreement regarding study selection was resolved by consensus. the process of extracting data from included studies was done independently by two reviewers using the previously specified excel form. the data extracted from each study included the name of the first author, the country, the number of subjects under investigation, the disease of the population under investigation, and the type of poct test and the final result. 2.5. quality assessment the quality check was done using the appropriate checklist from the scottish intercollegiate guidelines network (sign) methodology checklist and risk of bias 2 (rob 2) tool checklist for rcts (17). two independent reviewers evaluated the studies based on the checklists and in case of non-agreement a third reviewer judged. 3. results after reviewing 3708 article titles and removing 1035 items due to duplication, 2673 article titles were examined. after removing 1007 unrelated titles, among the remaining 666 articles that were reviewed in terms of abstracts, 487 cases were removed due to irrelevance. the full texts of the 179 remaining articles were reviewed. studies that met the inclusion criteria of this study were selected. finally, 16 studies were included in this systematic review (18-33). figure 1 shows how the studies were selected. the baseline characteristics of these studies are shown in table 1. there were 5 rct studies (18, 21, 25, 28, 29), 5 retrospective cohorts (22, 23, 30, 32, 33), 2 prospective cohorts (24, 31), and 4 before-after studies (19, 20, 26, 27). a total number of 100,224 participants were evaluated in these studies. all studies were conducted in the ed setting, except for one study of prehospital ems air medical transport. five studies used panels of poct and 3 had evaluated poct ultrasound for diagnosis of pericardiocentesis and hemodynamic instability. three studies evaluated lactate as the poct for diagnosis of sepsis and critically ill circumstances. cardiac parameters were used in 4 studies (20, 21, 26, 29). renal function was assessed as poct in 4 studies (25, 27, 28, 31) and poct echocardiography was used in one study (23). we only found one study about the poct influenza pcr that had reported the outcome of time to intervention (24). regarding the outcome measures, studies with many types of patients referring to ed had used different indices of time to intervention or time to disposition. studies on different shock circumstances had used time to first bolus of hydration or vasopressor or iv antibiotics for septic shock patients and central venous catheterization (cvc) placement time. time to imaging was considered as the outcome in some studies on the poct echocardiography. although there were no comparisons to non-poct, since it is not possible in the setting of the resuscitation, we included the study and outcome was the occurrence of intracardiac thrombus during cardiac arrest, which can be considered as the time of the end of resuscitation. in synthesis of the evidence, all included studies were reporting the benefits of the poct on decreasing the time to proper interventions ad increasing the time to negative interventions in the last lines of critical care as well as intubation and cvc placement. overall, time to intervention was not homogenously reported in the literature but all poct utilizations were associated with more rapid decision-making. the possibility of adverse events or complications due to the unnecessary interventions in cases of false positive or negative results of the poct remains the major problem in drawing the final conclusion in the review. this raises the question whether samples should be sent for laboratory testing at the same time as performing the poct or after a positive poct. 3.1. quality assessment risk of bias 2 (rob 2) tool checklist was used for 5 rct studies (table 2). none of these rcts were blinded. there was an overall high risk of bias, especially in case of the randomization methods, and non-blinded designs. the effects of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. rahsepar et al. 4 the false negative poct care were not accurately addressed in the evaluated literature, increasing the possibility of noninvestigated potential harms. sign checklist was used for other cohorts and before-after studies (table 3). most studies’ quality was compromised by some points. diagnosis of most diseases is/was made based on clinical findings, imaging, and laboratory findings. in studies with mixed types of patients, study results might have been affected by the diagnosis based on other clinical findings, rather than the laboratory finding alone (bias of having an outcome in enrolment). only singer et al. b, lau et al. (predict study), perlitz et al., deledda et al., and hoch et al. had homogenous patients regarding the type of the disease. 4. discussion many systematic review studies have focused on the advantages and disadvantages of using poct in the emergency room. the belief that drives poct is to make the test convenient and fast for the patient. these devices make it more likely that the patient, physician, and care team will receive results more quickly, thus allowing "clinical management" decisions to be made immediately. this assumption was assessed in our study. various pocts have been marketed: glucometers, blood gas and electrolyte analyzers, etc. pocts are cheaper, faster, and smarter and, by making poct more affordable, the tendency to use them for many diseases has increased (6, 7). the accuracy of established diagnoses based on poct was not taken into account in our investigation, but overall, outcomes of interest, i.e. times to the intervention, were not consistently reported by literature. however, all poct utilizations were associated with a quicker decision-making process, which would be highly interesting to both healthcare providers and policy-makers. the likelihood of adverse events or consequences from unneeded procedures when poct findings are falsely positive or negative still poses a serious obstacle to making a definitive decision. this raises the question whether samples should be sent for laboratory testing at the same time as performing the poct or following a positive poct. this problem raises questions regarding the treatment’s ultimate results, but it should be evaluated according to each patient’s unique medical situation and the available poct. these results were not comparable to any study as there was no study with similar objectives. major benefits are achieved when poct device output is readily available to the care team in an electronic medical record (reduced turnaround time or tat), and mortality is reduced when goal-directed therapy (gdt) is combined with poct and use of electronic medical records. but our review has indicated the need for treatment confirmation as a factor limiting the application of poct, especially in new pocts. singer et al. (2015) provided the evidence that in timecritical patients with severe conditions, using the poct of hemoglobin (hb), international normalized ratio (inr), troponin, and some other tests decreased the time to computed tomography (ct) with intravenous contrast injection, while their utilized poct did not included any parameters needed for the estimation of the kidney function. but other studies that had evaluated renal function pocts had not evaluated the time to ct scan metrics except for bargnoux et al. (27). in addition, poct has become established worldwide and plays a vital role in critical care. best poct known to the public is the blood sugar (bs) assessment tool. a review by beik et al. evaluated the poct in hyper/hypoglycemic state. their results were supporting the application of the poc β-hydroxybutyrate and bs tests in patients with suspected diabetes-related ketoacidosis (34). assessment of blood sugar is one of the vitals of the critical care, for which poct has been routinely made available. but the application of the other new pocts is also growing. our review included many new poct items, all of which satisfied the needs of the ed for quick disposition and decisionmaking for patients. we compared the care with and without the poct in the ed setting. some ongoing trials with good power were not included in our study due to being limited to the comparison framework; a trial of the laphsus was not included in our study as they had not compared poct with non-poct-based care (35, 36). one of the most common uses of poct in ed is for patients with suspected sepsis, for whom timely intervention is of great importance. while we did not assess the safety issues, the systematic review of kruse et al. only focused on the accuracy of lactate poct in sepsis care and showed promising results (37). morris et al. conducted the most similar review to our study. they included 8 studies about sepsis but only 2 of the studies had reported time to intervention indices (38). while our review showed positive results in decreasing the time to intervention of almost all evaluated interventions in different medical circumstances of poct application, a study showed that accelerating the speed of the laboratory analysis in stroke care did not change door-to-needle time (39); yet, there were not using the bedside tests and only the laboratory works were speeded up. our review included many new poct items, all of which satisfied the needs of the ed for quick disposition and decisionmaking for patients. this study revealed the methodological and conceptual limitations of the poct literature in the time metric studies in the ed. 5. limitations since there were multiple diverse reported outcomes based on utilizing different pocts in diverse types of diseases, we this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e82 were not able to conduct any meta-analysis. also, the quality of the included studies was not satisfactory and most studies suffered from significant methodological limitations that warrant the need for randomized trials or protocols for standard evaluation of the exposure and outcomes in the cohorts, for minimizing the risk of bias. outcome level risk of bias assessment in this study is complex due to diverse outcomes. most studies’ quality was compromised by some points. diagnosis of most diseases was made based on clinical findings, imaging, and laboratory findings. in studies with mixed types of patients, study results might have been affected by the diagnosis based on other clinical findings, rather than the laboratory finding alone (bias of having an outcome in enrolment). only singer et al. b, lau et al. (predict study), perlitz et al., deledda et al., and hoch et al. had homogenous patients regarding the type of the disease. although we used a comprehensive literature review, there might be some studies that were not found by our study due to incomplete retrieval of identified research or some studies might not have been published due to negative results or any other publishing issues, causing reporting bias. 6. conclusion in synthesis of the evidence, all included studies were reporting the benefits of poct in decreasing the time to proper interventions and increasing the time to negative interventions in the last lines of critical care as well as the intubation and cvc placement. 7. declarations 7.1. acknowledgments we appreciate clinical research development unit of peymanieh educational and research and therapeutic center of jahrom university of medical sciences for providing facilities for this work. 7.2. authors’ contribution sr and pa designed the study. sr, msj, sa, and ra wrote the protocol. ha, pa, ba, and fm conducted the literature review and data extraction. sah, brk, nk, and sr wrote the draft of the article. all authors contributed to revisions and confirmed the final version of the article. 7.3. funding none. 7.4. conflict of interest none. references 1. luppa pb, müller c, schlichtiger a, schlebusch h. pointof-care testing (poct): current techniques and future perspectives. trac trend in anal chem. 2011 jun 1;30(6):887-98. 2. quinn ad, dixon d, meenan bj. barriers to hospitalbased clinical adoption of point-of-care testing (poct): a systematic narrative review. crit rev clin lab sci. 2016 jan 2;53(1):1-2. 3. wiencek j, nichols j. issues in the practical implementation of poct: overcoming challenges. expert rev mol diagn. 2016 apr 2;16(4):415-22. 4. tideman p, simpson p, tirimacco r. integrating poct into clinical care. the clinic biochem rev. 2010 aug;31(3):99. 5. francis aj, martin cl. a practical example of poct working in the community. the 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jp. pointof-care creatinine testing in patients receiving contrastenhanced computed tomography scan. clinic chim acta. 2018 mar 1;478:111-3. 28. chaisirin w, wongkrajang p, thoesam t, praphruetkit n, nakornchai t, riyapan s, ruangsomboon o, laiwejpithaya s, rattanathummawat k, pavichai r, chakorn t. role of point-of-care testing in reducing time to treatment decision-making in urgency patients: a randomized controlled trial. west j of emerg med. 2020 mar;21(2):404. 29. mogensen cb, borch a, brandslund i. point of care technology or standard laboratory service in an emergency department: is there a difference in time to action? a randomised trial. scand j trauma resusc emerg med. 2011 dec;19(1):1-6. 30. kankaanpää m, holma-eriksson m, kapanen s, heitto m, bergström s, muukkonen l, harjola vp. comparison of the use of comprehensive point-of-care test panel to conventional laboratory process in emergency department. bmc emerg med. 2018 dec;18(1):1-6. 31. jarvis p, davies m, mitchell k, taylor i, baker m. can the introduction of point-of-care testing for renal function in the emergency department reduce overcrowding?. point of care. 2015 mar 1;14(1):42-4. 32. mosier jm, stolz u, milligan r, roy-chaudhury a, lutrick k, hypes cd, billheimer d, cairns cb. impact of pointof-care ultrasound in the emergency department on care processes and outcomes in critically ill nontraumatic patients. crit care explor . 2019 jun 26;1(6):e0019. doi: 10.1097/cce.0000000000000019. ecollection 2019 jun. 33. hall mk, taylor ra, luty s, allen ie, moore cl. impact of point-of-care ultrasonography on ed time to disposition for patients with nontraumatic shock. am j emerg med . 2016 jun;34(6):1022-30. doi: 10.1016/j.ajem.2016.02.059. epub 2016 feb 27. 34. beik n, terry k. improving glucose management with point-of-care testing in the emergency department. cur emrg and hosp med rep. 2014 sep;2(3):166-71. 35. jouffroy r, léguillier t, gilbert b, tourtier jp, blochlaine e, ecollan p, bounes v, boularan j, gueye-ngalgou p, nivet-antoine v, beaudeux jl. pre-hospital lactatemia predicts 30-day mortality in patients with septic shock—preliminary results from the laphsus study. j clinic med. 2020 oct 14;9(10):3290. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e82 36. jouffroy r, leguillier t, gilbert b, tourtier jp, bloch-laine e, ecollan p, bounes v, boularan j, gueye-ngalgou p, nivet-antoine v, beaudeux jl. prehospital lactate clearance is associated with reduced mortality in patients with septic shock. am j emerg med. 2021 aug 1;46:36773. 37. kruse o, grunnet n, barfod c. blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. scand j trauma resusc emerg med. 2011 dec;19(1):1-2. 38. morris e, mccartney d, lasserson d, van den bruel a, fisher r, hayward g. point-of-care lactate testing for sepsis at presentation to health care: a systematic review of patient outcomes. brit j of genral pract. 2017 dec 1;67(665):e859-70. 39. trongnit s, reesukumal k, kost gj, nilanont y, pratumvinit b. reducing laboratory turnaround time in patients with acute stroke and the lack of impact on time to reperfusion therapy. arch pathol lab med. 2021 may 2. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. rahsepar et al. 8 table 1: the basic characteristics of included studies id design setting n poct type patients comparison result of time to intervention mullen et al. (18) rct pre hospital 59 fingerstick lactate critically ill poct vs. no test higher time to central venous catheter (cvc) placement singer et al. a (19) before-after study ed 160 hand-held lactate poct (i-stat) sepsis suspected poct vs. standard care lower time to iv fluids, icu admissions; similar time to iv antibiotics singer et al. b (20) before-after study ed 23 86 panel of hb and hct, troponin i, bnp, lactate, and inr critical patients poct vs. standard care lower time to contrast ct (only for hb and hct) goodacre et al. (21) rct ed 22 43 ck-mb, myoglobin, troponin i [siemens] mi suspected poct vs. standard care higher rate of cardiac intervention in first 24 hours hoch et al. (22) retrospective cohort ed 25 7 ultrasound pericardiocentesis poct vs. no test lower time to intervention lau et al. (predict study) (23) retrospective cohort ed 56 resuscitative echocardiography intracardiac thrombus during cardiac arrest poct positive vs. negative immediate termination of resuscitation perlitz et al. (24) cross-over design, prospective ed 82 8 influenza pcr influenza suspected poct vs. standard care lower admission time to antiviral therapy lee et al. (25) rct ed 23 23 liver, renal, pancreas enzymes, and lipid panels, electrolytes, and blood gases ed patients poct vs. standard care lower time to intervention in almost all interventions deledda et al. (26) before-after study ed 54,41 9 cardiac troponin i mi suspected poct vs. standard care lower disposition time bargnoux et al. (27) before-after study ed 17 8 creatinine contrastenhanced computed tomography scan poct vs. standard care lower waiting time for imaging chaisirin et al. (28) rct ed 26 0 panel of metabolic, electrolyte, bun, creatinine, co2 ed patients poct vs. standard care lower disposition time mogensen et al. (29) rct ed 22 2 d-dimer, troponin i, ck-mb, crp ed patients poct vs. standard care lower time to intervention only for acute bacterial infection (crp) kankaanpää et al. (30) retrospective cohort ed 17 59 blood gases and chemistry panel, cbc, and crp non-ambulatory ed patients poct vs. standard care lower time to imaging jarvis et al. (31) prospective cohort ed 25 70 9 renal function analysis ed patients poct vs. standard care lower time to intervention mosier et al. (32) retrospective cohort ed 5,4 41 ultrasound hemodynamic instability poct before iv therapy or vasopressor vs. no poct no poct group had the least time of intubation, followed by group of poct after bolus water or vasopressor hall et al. (33) retrospective cohort ed 38 34 ultrasound shock poct vs. standard care lower disposition time poct: point-of-care testing; rct: randomized clinical trial; n: sample size; ed: emergency department; hb: hemohlobolin; inr: the international normalized ratio; ck-mb: creatine kinase mb; bun: blood urea nitrogen; ct: computed tomography; icu: intensive care unit; iv: intravenous; pcr: polymerase chain reaction; hct: hematocrit; mi: myocardial infarction; bnp: b-type natriuretic peptide; crp: c-reactive protein; cbc: complete blood count. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e82 figure 1: prisma flowchart of articles included in the review study. poct: point-of-care testing. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. rahsepar et al. 10 table 2: critical appraisal of randomized clinical trials included in the review study randomization concealment imbalance suggest problem? risk of bias mullen et al. probably no no yes high goodacre et al. yes yes yes low lee et al. yes probably no yes some concerns chaisirin et al. yes yes yes low mogensen et al. yes yes yes low table 3: critical appraisal of cohort studies included in the review character singer et al. singer et al. singer et al. hoch et al. lau et al. perlitz et al. deledda et al. bargnoux et al. kankaanpää et al. jarvis et al. mosier et al. hall et al. clear question y y y y y y y y y y y y comparable source populations y y y y y y y y y y y y bias of having outcome in enrolment y y y y y y y y y y y y lost to follow-up reported and compared? n n n y n n n n n n n n clear outcomes y y y y y y y y y y y y blinding n n n n n n n n n n n n knowledge of exposure status y y y y y y y y y y y y reliable exposure assessment y y y y y y y y y y y y validity and reliability of assessment based on other sources n n n n y n n n n n n n exposure repeated assessment n n n n y n n n n n n n identified confounders y y y y y n y y y y y y confidence intervals reported? y n y y y n y n y y y y risk of bias? ** * 0 0 0 ** 0 ** ** ** 0 0 association between exposure and outcome? y y y y y y y y y y y y clinical application y y y y y n y y y y y y n: no; y: yes. risk of bias has 3 levels of 0, *, **, where ** is showing the highest risk of bias and 0 for low source of bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e39 rev i ew art i c l e needle direction and distance of arteriovenous fistula cannulation in hemodialysis adequacy; a systematic review and meta-analysis samad karkhah1,2, majid pourshaikhian3, pooyan ghorbani vajargah1,2, morteza zaboli mahdiabadi4, amirabbas mollaei1,2, saman maroufizadeh5, seyed javad hosseini6, joseph osuji7, mohammad taghi moghadamnia3∗ 1. department of medical-surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 2. burn and regenerative medicine research center, guilan university of medical sciences, rasht, iran. 3. department of prehospital emergency medicine, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 4. student research committee, shahid sadoughi university of medical sciences, yazd, iran. 5. department of biostatistics and epidemiology, school of health, guilan university of medical sciences, rasht, iran. 6. department of nursing, esfarayen faculty of medical sciences, esfarayen, iran. 7. school of nursing and midwifery, faculty of health, community, and education, mount royal university, calgary, ab, canada. received: march 2023; accepted: april 2023; published online: 20 may 2023 abstract: introduction: this systematic review and meta-analysis aimed to summarize the evidence regarding the impact of needle direction and distance of arteriovenous fistula (avf) cannulation on kt/v (where k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea) and access recirculation (ar) as hemodialysis (hd) adequacy criteria. methods: a comprehensive systematic search was performed on international and domestic electronic databases from the earliest to june 4, 2022 using keywords. analysis was performed in stata software v.14. results: three randomized control trials (rcts) and four non-rct articles were included in the final review. six studies reported the effects of direction, while four mentioned the effects of distances of avf cannulation on outcomes of hd adequacy based on kt/v or ar. results of three non-rct studies showed that retrograde direction decreased kt/v more than antegrade direction (es: 0.44, 95% ci: -0.38 to 1.27). two non-rct studies showed that antegrade decreased ar compared to the retrograde direction (es: -0.64, 95%ci: -1.94 to 0.67). however, the results of two rcts indicated uncertainty about this issue. two of the four studies suggested that a distance of 5 cm or more in arterial and venous needles had greater adequacy than a distance of less than 5 cm. however, other studies did not confirm this finding. conclusion: overall comparison of the results qualitatively and quantitatively indicated uncertainty about the effects of direction and distance of avf cannulation on hd adequacy outcomes. more studies with high-quality designs, such as rcts, are required to better understand and adjudicate the effects of needle direction and distance of avf cannulation on hd adequacy outcomes. keywords: vascular access devices; arteriovenous fistula; catheterization; renal dialysis cite this article as: karkhah s, pourshaikhian m, ghorbani vajargah p, zaboli mahdiabadi m, et al. needle direction and distance of arteriovenous fistula cannulation in hemodialysis adequacy; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e39. https://doi.org/10.22037/aaem.v11i1.1943. ∗corresponding author: mohammad taghi moghadamnia; department of prehospital emergency medicine, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. email: moghadamnia@gums.ac.ir, tel: +989113312939, orcid: https://orcid.org/0000-0002-3380-5142. 1. introduction as chronic renal failure progresses to end-stage renal disease (esrd), maintaining the quality of life and survival depend on the effectiveness of kidney replacement therapies (krt), including hemodialysis (hd), peritoneal dialysis, and kidney transplantation (1). it was estimated that 4.9-9.7 million people required krt in 2010 (2). the main objective of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 2 these treatments (hd or kidney transplantation) is to reduce life-threatening consequences and ultimately reduce deaths from uremia (3). transplantation is superior to hd in improving quality of life, ensuring more prolonged survival, and lowering costs. however, hd is widely used in cases where transplantation is impossible and as a maintenance krt (1, 4). hd accounts for 89% of treatments for esrd patients worldwide (5). adequate hd requires reliable vascular access (va). if proper va is not possible, the consequence will be prolonged hospitalisation and increased costs (6). there are three types of va for hd: arteriovenous fistulas (avfs), arteriovenous grafts, and central venous catheters (7). avf is the optimal method for va due to its fewer complications, reduced mortality rate, and increased durability compared to other va types (8). for each hd, two needles are used to cannulate the fistula (9). the arterial needle is responsible for drawing blood from the patient, while the venous needle is used to return the purified blood (10). in the usual approach, the arterial needle is placed at least 3 cm from the anastomosis site with the flow towards the end of the limb (retrograde) or heart (antegrade) and should be at least 5 cm away from the venous needle (11). proper distance and direction of needles inserted into the avf can reduce recirculation and thus, increase hd quality (8, 11). proper needle placement, prevents increased frequency or duration of hd, which puts patients at a lower risk of infections and incurs increased costs (12). hd access recirculation (ar), in any case, reduces the quality of hd (13). therefore, ar measurement can be considered an acceptable method for evaluating the quality of hd (14). ar is detected in hd when dialyzed blood returns to the dialysate through an arterial needle instead of entering the systemic circulation after returning by the venous needle (15). various factors can cause ar, including improper needle insertion, fistula stenosis, and mechanical stenosis at the end of the vein (16). there are conflicting findings on the effect of the direction and distance of needles on the quality of hd. a study by lim et al. showed no significant difference between the antegrade and retrograde cannulation methods and their needle distance regarding the amount of ar (17). on the other hand, the results of another study by vahedi et al. showed that ar in antegrade cannulation and a 3 cm needle distance was significantly higher than in a retrograde manner with a 6 cm needle distance (13). therefore, given the importance of the subject and the contradictory findings in this regard, this systematic review and meta-analysis aimed to summarize the evidence regarding the impact of needle direction and distance of avf cannulation on hd adequacy. 2. methods 2.1. study registration and reporting the present systematic review and meta-analysis was conducted based on the preferred reporting items for systematic reviews and meta-analysis (prisma) checklist (18). however, this review study has not been registered in the international prospective register of systematic reviews (prospero) database. 2.2. patient/population, intervention, comparison, and outcomes (pico) framework the pico framework was used to clarify the purpose of the study. accordingly, population (articles in which patients with avf cannulation were examined), intervention (studies that compared needle direction and distance of avf cannulation), and comparison (studies that had control or placebo groups to compare with the intervention groups), and finally, outcome (studies that measured the adequacy of hd based on kt/v and ar in relation to the insertion of the catheter in the avf), were considered when including studies in the systematic review and meta-analysis. 2.3. search strategy a comprehensive systematic search was performed on international electronic databases such as scopus, pubmed, web of science, and iranian electronic databases such as iranmedex, and scientific information database (sid) with keywords extracted from medical subject headings such as "vascular access", "arteriovenous fistula", "graft", "catheterizations", "puncture”, “cannulation”, “hemodialysis”, “dialysis adequacy”, and “recirculation” from the earliest to june 4, 2022. for example, the search strategy in pubmed/medline database included such search terms as ((“vascular access”) or (“arteriovenous fistula”) or (“graft”) or (“catheterizations”) or (“puncture”) or (“cannulation”) or (“needle distance”) or (“needle direction”)) and ((“hemodialysis”) or (“renal dialysis”) or (“hd”)) and ((“renal circulation”) or (“dialysis adequacy”) or (“recirculation”)). keywords were combined with boolean operators "and" and "or". similar to the method mentioned in the keyword search, persian equivalents of the words were searched in iranian electronic databases. the search was performed by two researchers, independently. items such as expert opinions, conference presentations, dissertations, research and committee reports, and ongoing research, known as the gray literature, were not included in this systematic review. gray literature includes articles produced in print and electronic formats but not peer-reviewed or evaluated by a commercial publisher (19). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e39 2.4. inclusion and exclusion criteria rcts and non-rct studies in english and persian, focusing on the effect of direction of avf cannulation or needle distance on hd adequacies such as kt/v, urea reduction ratio (urr), and recirculation in the hd patients were included in this study. letters to the editor, case reports, qualitative studies, and reviews were excluded. 2.5. study selection data management was performed using endnote 8x software. two researchers independently evaluated the eligibility of studies for inclusion based on pre-determined inclusion and exclusion criteria. studies included in this review were selected after eliminating duplicates, evaluating titles and abstracts, and reviewing the full texts of the selected articles. a third researcher resolved any differences and contradictions between the other two researchers. finally, the resource list was evaluated manually to prevent data loss. 2.6. data extraction and quality assessment the joanna briggs institute ( jbi) critical appraisal checklist was used to assess the quality of randomized control trials (rcts) and non-rcts studies (20). this tool assesses the internal validity, the similarity of participants of compared groups, the reliability of outcomes measured, and the appropriateness of statistical analysis of rct and non-rct studies in 13 and 9 items, respectively. in this systematic review and meta-analysis, researchers extracted information including first author name, year of publication, location, design, sample size, type of intervention, duration of the study, duration of intervention and follow-up, male/female ratio, age, type of control group, tool characteristics, specific statistical tests, and key results of studies. the quality of the studies in this systematic review and meta-analysis was evaluated by two researchers, separately, using a three-point reading range that included "yes" (score 1), "no" (score 2), and "not applicable / not clear" (score 0) (20). the quality assessment levels of the studies in the jbi checklists were good (≥8), fair (6-7), and poor (≤5) (21). 2.7. hd adequacy assessment techniques 2.7.1. kt/v kt/v, where k is the dialyzer urea clearance (expressed in liters per hour), t is the duration of dialysis (expressed in hours), and v is the volume of distribution of urea, is a dimensionless ratio that represents fractional urea clearance (expressed in liters) (22). a level less than 0.8 indicates insufficient hd (23). 2.7.2. ar blood is typically pumped from the dialysis access at 300 to 500 cc/min during hd. a failing av access can significantly reduce flow to less than the hd machine’s blood pump rate. this situation can result in some dialyzed blood exiting the dialyzer through the venous needle and then reentering the dialyzer through the arterial side to support the extracorporeal blood flow rate set by the blood pump. this condition is known as ar (24, 25). 2.7.3. urr another method of measuring hd adequacy is urr. this method is calculated using the formula (pre-urea – posturea/pre-urea) in hd (26). the acceptable level of urr is 65% and above (23). a urr of less than 65% is linked to higher patient morbidity and mortality. the mortality rate was observed to drop by up to 11% for every 5% rise in urr (27). 2.7.4. ultrasound-based technique the ultrasound dilution (usd) method measures access flow (qa) during hd. the advantages of the usd technique include being easy to use and providing an immediate response. qa is measured through usd using the formula (qa=qb(1-r/r)), where qb is the dialyzer blood flow rate and r is the fraction of recirculated blood entering the dialyzer (28). 2.8. statistical analysis analysis was performed using stata software v.14. heterogeneity was measured using i2 statistic. 0% to 40% was considered unimportant; 30% to 60%: may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; and 75% to 100% considerable heterogeneity. due to the considerable heterogeneity between studies, the random effect model and inverse-variance method were used to estimate the mean difference. since rcts and non-rct studies have different weights in the evidence hierarchy pyramid, each should be analysed separately. a confidence interval of 95% was considered a significant level. pooled effect size related to the effects of needle direction on the kt/v and ar was reported on a forest plot. 2.9. publication bias although the number of effect sizes related to the effect of needle direction on the kt/v and ar was less than 10, a publication bias test was performed. the funnel plot and result of the egger’s test were used to assess publication bias. 2.10. sensitivity analysis sensitivity analysis was performed to determine the pooled effect sizes related to the effect of needle direction on the kt/v and ar. 2.11. certainty of evidence the certainty of the evidence was assessed through the grade of recommendation, assessment, development, and evaluation (grade) approach. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 4 table 1: basic characteristics of the studies included in this systematic review first author/year location study characteristics* male/ female ratio (%) age (year) mean(sd) control group tool characteristics specific statistical tests key results jbi score dias et al., 2008 (29) brazil 1. quasiexperimental 2. 174 3. antegrade vs. retrograde cannulation with distance between needles more than 5 cm vs. less than 5 cm 4. n/a 5. 4 hours 6. 0 59.77/ 40.23 51.90 (15.57) n/a • kt/v • ar • anova • pearson linear correlation • kt/v in the group of retrograde cannulations with 5 cm or more distance between needles was higher than in other groups (except temporary double lumen catheter group) (p<0.05). • ar in the group of retrograde cannulations with 5 cm or more distance between needles was lower than in other groups (p<0.05). fair ozmen et al., 2008 (30) turkey 1. quasiexperimental 2. 22 3. antegrade vs. retrograde cannulation 4. 8 weeks 5. n/a 6. 0 n/a n/a n/a kt/v t-test there was no significant difference between antegrade and retrograde cannulation in the amount of kt / v (p=0.123). fair rothera et al., 2011 (10) uk 1. rct (crossover) 2. 12 3. cannulation with distance between needles 5 cm vs. 2.5 cm 4. n/a 5. n/a 6. 0 n/a n/a the distance between the two needles in five consecutive hd sessions was 5 cm in half of the participants and 2.5 cm in the same number of hd patients. • ar • blood access flow rate • eid • kolmogorov– smirnov normality test • shapiro– wilk normality test • paired ttest • the blood access flow rate was significantly higher when the distance between the two needles was 2.5 cm than when the distance between the two needles was 5 cm (p=0.014). • there were no significant differences between 2.5 and 5 cm needle distances in the amount of eid (p=0.139). good reyes, 2016 (31) philippines1. rct 2. 20 (10/10) 3. antegrade vs. retrograde cannulation 4. n/a 5. n/a 6. 0 n/a n/a arterial needles in avfs were implanted in this group as antegrade. • urr • kt/v • ar n/a • the urr in antegrade cannulation was significantly higher than in retrograde cannulation (p<0.05). • the kt/v in antegrade cannulation was significantly higher than in retrograde cannulation (p<0.05). • there was no significant difference between antegrade and retrograde cannulation in the amount of ar (p>0.05). good elias et al., 2018 (11) france 1. quasiexperimental 2. 14 3. antegrade vs. retrograde cannulation in distance between needles 2.5 cm 4. n/a 5. n/a 6. 0 57.14/42.86 62.30 (15.57) participants underwent hd three times with arterial needles in antegrade cannulation and then with arterial needles in retrograde cannulation. • kt/v • ar • nonparametric paired test • signed rank test • there was no significant difference between the antegrade and retrograde cannulation with a 2.5 cm distance between needles in the amount of kt/v (p=0.20). • there was no significant difference between the antegrade and retrograde cannulation with a 2.5 cm distance between needles in the amount of ar (p>0.05). fair this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e39 table 1: basic characteristics of the studies included in this systematic review first author/year location study characteristics* male/ female ratio (%) age (year) mean(sd) control group tool characteristics specific statistical tests key results jbi score lim et al., 2018 (17) south korea 1. quasiexperimental 2. 30 7. antegrade vs. retrograde cannulation with distance between needles 7 cm vs. 5 cm 4. 3 weeks 5. n/a 6. 0 43.33/56.67 55.50 (13.21) n/a ar anova there was no significant difference between the antegrade and retrograde cannulation and their needle distance in the amount of ar (p=1.00). fair vahedi et al., 2018 (13) iran 1. rct 2. 22 8. antegrade vs. retrograde cannulation with distance between needles 3 cm vs. 6 cm 4. n/a 5. 4 hours 6. 0 54.55/45.45 53.00 (16.75) n/a ar • generalized estimating equations • odds ratio the ar in antegrade cannulation and 3 cm needles distance was significantly higher than in retrograde manner and 6 cm needles distance (p<0.05). good rct: randomized clinical trial; hd: hemodialysis; ar: access recirculation; eid: effective ionic dialysance; urr: urea reduction rate; anova: analysis of variance; jbi: joanna briggs institute; kt/v: k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea; avf: arteriovenous fistula; n/a: not available. *:1. design; 2. sample size (i/c); 3. intervention; 4. duration of study; 5. duration of intervention; 6. duration of follow-up. 3. results 3.1. study selection as shown in figure 1, after a thorough search of electronic databases, 2,228 articles were obtained. after deleting 402 duplicate articles, 1,826 articles remained. after reviewing the titles and abstracts of the articles, 1,634 articles were excluded from the study due to discrepancies with the research purpose. then another 126 articles were excluded due to their non-experimental design. full-text evaluation of the remaining 56 articles led to the elimination of another thirtyfour due to poor design and results. another fifteen articles were excluded due to a lack of appropriate information. finally, this systematic review and metaanalysis utilized seven studies (10, 11, 13, 17, 29-31). 3.2. study characteristics as mentioned in tables 1 & 2, a total of 294 hd patients entered this systematic review and meta-analysis in seven studies (10, 11, 13, 17, 29-31). their mean age was 55.67 (sd = 15.27) years. 53.69% of the patients were male, and 96.60% were in the intervention group. four studies (11, 17, 29, 30) had non-rct, and three (10, 13, 31) had rct designs. of the studies in this systematic review, two (17, 30) reported an average study duration of 5.5 weeks. two studies (13, 29) also reported a duration of intervention that averaged 4 hours. to assess hd adequacy, six studies (10, 11, 13, 17, 29, 31) used ar, 4 articles (11, 29-31) used kt/v, one study (10) used blood access flow rate, while one other study (10) used effective ionic dialysance (eid). also, one study (31) used urea reduction rate (urr). the studies included in this review were conducted in brazil (29), france (11), iran (13), the philippines (31), south korea (17), turkey (30), and the uk (10). three studies (10, 11, 31) had control groups. 3.3. methodological quality assessment of eligible studies as shown in figures 2 and 3, of the seven studies (10, 11, 13, 17, 29-31), two (10, 11) had a good quality level, while five (13, 17, 29-31) had an acceptable quality level. 3.4. effect of needle direction in avf cannulation on hd adequacy based on kt/v four studies (11, 29-31) (one rct (31) and three non-rcts (11, 29, 30)) reported the effects of direction on hd adequacy based on kt/v. the rct study (31) indicated that antegrade direction improved hd adequacy. this study did not report a standard deviation (31). therefore there was insufficient data to report the effects of direction on kt/v and ar based this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 6 table 2: interventions of the studies included in the systematic review first author/ year intervention program description dias et al., 2008 (29) antegrade and retrograde cannulation patients undergoing hd were divided into the following five groups: • group 1: the placement of the needles in this group was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other in this group was 5 cm or more. • group 2: the placement of the needles in this group was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other in this group was less than 5 cm. • group 3: the placement of the needles in this group was antegrade, with both arterial and venous sets pointing toward the heart. the distance of the needles from each other in this group was 5 cm or more. • group 4: the placement of the needles in this group was antegrade, with both arterial and venous sets pointing toward the heart. the distance of the needles from each other in this group was less than 5 cm. • group 5: in this group, patients had a temporary double lumen catheter. to evaluate kt / v, five blood samples of 3 to 5 ml were taken before and after hd. also, to evaluate ar, three blood samples were taken from arterial and venous sets and limb contralateral to va. ozmen et al., 2008 (30) antegrade and retrograde cannulation participants underwent two different interventions for hd, as follows: • month 1: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. • month 2: the placement of the needles was antegrade, with both arterial and venous sets pointing toward the heart. blood samples were taken before and after hd in the middle of the treatment week and four times a month in each direction. rothera et al., 2011 (10) antegrade cannulation the distance between the two needles in five consecutive hd sessions was 5 cm in half of the participants and 2.5 cm in the same number of hd patients. in the other overall, a maximum of 60 hd sessions were performed for each group. during each hd, ar was measured as a percentage, eid as an ml/min, and blood flow rate as an ml/min. eid was measured in the first half hour, one and a half hours, and the last half hour of hd. ar and blood flow rate were measured in the first half hour of hd. reyes, 2016 (31) antegrade and retrograde cannulation patients participating in this study were divided into two groups, as follows: • intervention group: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. • control group: the placement of the needles was antegrade, with both arterial and venous sets pointing toward the heart. blood samples were taken before hd, the first 30 minutes of hd, and after hd. urr, kt / v, and ar were used to evaluate the adequacy of hd. elias et al., 2018 (11) antegrade and retrograde cannulation participants underwent hd three times with arterial needles in antegrade cannulation and then with arterial needles in retrograde cannulation. the distance between hd needles was 2.5 cm. in general, a maximum of 84 hd sessions were performed on these patients. ar was measured in the first 30 minutes of hd and kt / v in the last 30 minutes of hd. lim et al., 2018 (17) antegrade and retrograde cannulation participants underwent three different interventions for hd, as follows: • week 1: the placement of the needles was antegrade, with both arterial and venous sets pointing toward the heart. the distance of the needles from each other was 7 cm. • week 2: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other was 5 cm. • week 3: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other was 7 cm. vahedi et al., 2018 (13) antegrade and retrograde cannulation participants underwent four different interventions for hd, as follows: • session 1: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other was 3 cm. • session 2: the placement of the needles was antegrade, with both arterial and venous sets pointing toward the heart. the distance of the needles from each other was 3 cm. • session 3: the placement of the needles was retrograde, with the arterial set toward the extremity of the arm and the venous set toward the heart. the distance of the needles from each other was 6 cm. • session 4: the placement of the needles was antegrade, with both arterial and venous sets pointing toward the heart. the distance of the needles from each other was 6 cm. to assess ar, a blood sample was taken 30 minutes after the start of hd, after the device was turned off, a blood sample was taken from the arterial line and a blood sample was taken from the venous line of the filter. hd: hemodialysis; eid: effective ionic dialysance; kt/v: k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea; ar: access recirculation; va: vascular access; urr: urea reduction rate. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e39 table 3: grade of recommendation, assessment, development, and evaluation (grade) approach summary for this study -outcome -number of included effect sizes number of participants risk of bias consistency directness precision publication bias summary of findings (effect size) quality -ar -3 -182 non-rct studies were included analysis considerable heterogeneity + was not detected* -0.64 (-1.94, 2.65) low -kt/v -4 -226 non-rct studies were included analysis considerable heterogeneity + was not detected * 0.44 (-0.38,1.27) low *: number of studies was less than 10. rct: randomized clinical trial; ar: access recirculation; kt/v: k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea. on rct studies. the results of three non-rct studies (11, 29, 30) showed that retrograde direction decreased kt/v more than antegrade direction. however, this difference was statistically insignificant (es: 0.44, 95%ci: -0.38 to 1.27, z=1.05, i2:87.0%, p=0.29, figure 4). 3.5. effect of needle direction in avf cannulation on hd adequacy based on ar five studies (11, 13, 17, 29, 31) (two rcts (13, 31) and three non-rcts (11, 17, 29)) reported the effects of direction on hd adequacy based on the ar. the results of two studies (one rct and one non-rct) (13, 29) showed that ar in the retrograde cannulation method is less than in the antegrade cannulation method. also, three studies (one rct and two nonrct) (11, 17, 31) did not show a significant difference in ar in the two antegrade and retrograde cannulation methods. one rct study (13) did not report sufficient data. therefore meta-analysis was not performed based on rcts. also, the results of three non-rct studies (11, 17, 29) showed that the antegrade direction decreased ar when compared to the retrograde direction, but it was not statistically significant (es: -0.64, 95%ci: -1.94 to 0.67, z=0.96, i2:92.5%, p=0.34, figure 5). 3.6. effect of needles’ distance in avf cannulation on hd adequacy based on kt/v of the studies included in this review, one non-rct study (29) reported the effect of needle distance in avf cannulation on hd adequacy based on kt/v. this study (29) suggested that a distance of 5 cm or more between arterial and venous needles had greater adequacy than a distance of less than 5 cm. 3.7. effect of needles’ distance in avf cannulation on hd adequacy based on ar of the studies included in this review, four studies (10, 13, 17, 29) reported the effect of needle distance in avf cannulation on hd adequacy based on ar. two studies (one rct and one non-rct) (13, 29) demonstrated that a distance of 5 cm or more between arterial and venous needles had greater adequacy and lower ar than a distance of less than 5 cm. however, one rct study (10) showed that a distance of 2.5 cm between arterial and venous needles had greater adequacy and lower ar than a distance of 5 cm. one non-rct study (17) did not show a significant difference between 5 cm and 7 cm needle distances in hd adequacy based on ar. 3.8. publication bias funnel plots indicated asymmetric views (figure 6); however, the results of the egger’s test did not confirm the presence of publication bias for effect sizes of ar (p=0.99) and kt/v (p=0.74). 3.9. sensitivity analysis sensitivity analysis showed that pooled effect size regarding the effect of directions on the kt/v was not dependent on a single study (95% ci: -0.62 to 1.77). in addition, pooled effect size regarding the effect of directions on the ar was not dependent on a single study, either (95% ci: -3.32 to 2.37). 3.10. certainty of the evidence the body of evidence assessed using the grade approach received an overall certainty rate of low for both outcomes (table 3). 4. discussion meta-analysis showed that retrograde direction decreased kt/v more than antegrade, but it was not statistically significant. also, the antegrade direction decreased ar compared to the retrograde; however, this was not statistically significant. one cross-sectional study showed that antegrade cannulation increases kt/v in hd patients (32). another crosssectional research found that the frequency of ar in the retrograde cannulation method was higher than in the antegrade method (33). in a study with 7,058 patients, parisotto et this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 8 figure 1: flow diagram of the study selection process. figure 2: methodological quality assessment of randomized clinial trial (rct) studies using joanna briggs institute ( jbi) checklist. al. (2014) indicated that the retrograde cannulation method would increase the risk of failure in hd (34). these findings were in line with the results of the current meta-analysis. another study found that most hd staff used the antegrade direction to access avf (35). the two rct studies included in the study showed controversial results. however, the results of other studies showed that direction has some impact on hd adequacy. therefore, the recommendation to use one particular direction is unsettled due to a lack of definitive evidence and guidelines on va give little importance to cannulation techniques . more studies with goodquality designs such as rcts are suggested. rct study design, after meta-analysis and systematic review studies, produce valid and reliable findings and researchers should conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e39 figure 3: methodological quality assessment of quasi-experimental studies using joanna briggs institute ( jbi) checklist. figure 4: effect size (es) comparison for the effect of antegrade and retrograde directions on kt/v. kt/v: k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea; ci:confidence interval. sider this characteristic. however, when there is limited evidence in studies with rct design, assessment of other designs, such as non-rct, becomes inevitable. we did not perform quantitative analysis to evaluate the efthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 10 figure 5: effect size (es) comparison for the effect of antegrade and retrograde directions on ar. ar: access recirculation; ci:confidence interval. figure 6: funnel plots of effect sizes (es) for ar (left) and kt/v (right). ar: access recirculation; kt/v: k is the dialyzer urea clearance, t, the duration of dialysis, and v, the volume of distribution of urea. fect of distance on dialysis adequacy criteria due to insufficient data in the articles. however, qualitative comparison of the results of the two rct and two non-rct studies indicated contradictory findings. one cause of ar is the lack of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e39 correct placement of avf, so reducing the distance between two needles can increase returning of dialyzed blood to the arterial line and thereby decrease hd adequacy (33). one cross-sectional study in iran showed that cannulation with a needle distance less than 5 cm had more ar and lower hd adequacy than other methods (33). heterogeneity between studies was considered significant based on i2 value. the source of heterogeneity can be related to the distance of needles, the number of sessions, and patients’ demographic characteristics in each study. certainty of evidence was evaluated and found to be at a low level based on the grade approach. results related to ar and kt/v based on the non-rcts studies showed that there are heterogeneity and wide confidence interval between studies. this finding again confirms the need for vigorous studies to better adjudicate the effects of distance and direction of the needle on hd adequacy. one of the most common ways of accessing blood vessels in patients with hd is an avf (36). patients under hd require va with proper functioning to survive (37). incorrect procedures in avf cannulation can reduce hd adequacy and increase ar (38). the current study showed that there are ambiguous issues about the effects of direction and distance of avf cannulation in hd patients. as a result, it is recommended that researchers pay more attention to this vital issue. 4.1. limitations this study had some limitations. meta-analysis was performed on the effects of direction on kt/v and ar based on non-rct studies since some of the included rct studies had insufficient data. we described the result of rcts qualitatively. although only seven articles were included in the review and analysis, this study can attract the attention of researchers and motivate them to conduct more studies with higher-quality designs on this topic. despite a comprehensive search of databases, not all studies on this subject may have been found, so it may have reporting bias. finally, only studies in english and persian were included in the present study, so it may have language bias. 4.2. implications for health managers and policymakers although the results of the meta-analysis suggested antegrade was more effective than retrograde, making any definitive recommendation based on this finding is problematic because of the low strength of the evidence. also, findings showed controversy and uncertainty about the effect of needle distance on hd adequacy outcomes. more rct studies and more data are required to make better evidence-based decisions regarding the effect of needle direction on hd efficacy. 4.3. implications for future research due to the heterogeneous nature of the results in this systematic review, it is suggested that researchers conduct more interventional studies to investigate the effect of antegrade and retrograde cannulation methods and needle distance on hd adequacy and ar. 5. conclusion overall, the findings from this study are inconclusive and support the uncertainty regarding the effects of directions and distances of avf cannulation. however, a meta-analysis based on non-rcts showed that antegrade direction had insignificant positive effects on hd adequacy, decreasing ar and improving kt/v. future rct studies are suggested to increase knowledge about the issue of needle direction and distances and their impacts on avf cannulation. 6. declarations 6.1. acknowledgments none. 6.2. conflict of interest the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. 6.3. fundings and supports this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. 6.4. authors’ contribution all authors have agreed on the final version of this manuscript. those listed as authors are qualified for authorship according to the following criteria: they have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; been involved in drafting the manuscript or revising it critically for important intellectual content; and have given final approval of the version to be published. each author participated sufficiently in the work, has taken public responsibility for appropriate portions of the content, and has agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 6.5. ethics approval this review study has not been registered in the international prospective register of systematic reviews (prospero) database. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. karkhah et al. 12 6.6. data availability the datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. references 1. van der tol a, lameire n, morton rl, van biesen w, vanholder r. an international analysis of dialysis services reimbursement. clin j am soc nephrol. 2019;14(1):84-93. 2. thurlow js, joshi m, yan g, norris kc, agodoa ly, yuan cm, et al. global epidemiology of end-stage kidney disease and disparities in kidney replacement therapy. am j nephrol. 2021;52(2):98-107. 3. gaudry s, palevsky pm, dreyfuss d. extracorporeal kidney-replacement therapy for acute kidney injury. n engl j med. 2022;386(10):964-75. 4. steinwandel u, davies h, gibson n. haemodiafiltration and haemodialysis should be reported separately by kidney replacement therapy registries. clin kidney j. 2022;15(6):1211-2. 5. sahathevan s, khor b-h, ng h-m, abdul gafor ah, mat daud za, mafra d, et al. understanding development of malnutrition in hemodialysis patients: a narrative review. nutrients. 2020;12(10):3147. 6. balamuthusamy s, miller le, clynes d, kahle e, knight ra, conway pt. american association of kidney patients survey of patient preferences for hemodialysis vascular access. j vasc access. 2020;21(2):230-6. 7. allon m. vascular access for hemodialysis patients: new data should guide decision making. clin j am soc nephrol. 2019;14(6):954-61. 8. gameiro j, ibeas j. factors affecting arteriovenous fistula dysfunction: a narrative review. j vasc access. 2020;21(2):134-47. 9. marticorena rm, dacouris n, donnelly sm. randomized pilot study to compare metal needles versus plastic cannulae in the development of complications in hemodialysis access. j vasc access. 2018;19(3):272-82. 10. rothera c, mccallum c, huang s, heidenheim p, lindsay rm. the influence of between-needle cannulation distance on the efficacy of hemodialysis treatments. hemodial int. 2011;15(4):546-52. 11. elias m, nnang-obada e, charpentier b, durrbach a, beaudreuil s. impact of arteriovenous fistula cannulation on the quality of dialysis. hemodial int. 2018;22(1):45-9. 12. ashoori m. a model to predict hemodialysis buffer type using data mining techniques. j health adm. 2017;20(67):99-110. 13. vahedi sa, aghaali m, ghanbari afra l, asayesh h, mashhadi f, saghafi h, et al. the effect of distance and direction of needle cannulation on the recirculation of arteriovenous fistula: a clinical trial. hayat. 2018;24(2):102-10. 14. trakarnvanich t, chirananthavat t, ariyakulnimit s, maneerat p, chabsuwan s. the efficacy of single-needle versus double-needle hemodialysis in chronic renal failure. j med assoc thai. 2006;89(suppl 2):s196-s206. 15. fakhry mm, khedr l, nour el din e. prevalence of access recirculation in prevalent arterio-venous (av ) fistula hemodialysis patients and its effect on hemodialysis adequacy. egypt j hosp med. 2018;72(6):4602-9. 16. mohseni r, ilali es. assessment of adequacy of dialysis in patients undergoing dialysis with bicarbonate solution. hayat. 2012;17(4):63-72. 17. lim hj, choi eh, kim ej, jeong jy, ban ss. the effect of arteriovenous fistula cannulation direction and puncture distance on the recirculation rate of hemodialysis patients. j korean crit care nurs. 2018;11(1):28-34. 18. page mj, mckenzie je, bossuyt pm, boutron i, hoffmann tc, mulrow cd, et al. the prisma 2020 statement: an updated guideline for reporting systematic reviews. bmj. 2021;372:n71. 19. corlett rt. trouble with the gray literature. biotropica. 2011;43(1):3-5. 20. fernández-férez a, ventura-miranda mi, camachoávila m, fernández-caballero a, granero-molina j, fernández-medina im, et al. nursing interventions to facilitate the grieving process after perinatal death: a systematic review. int j environ res public health. 2021;18(11):5587. 21. john jr, jani h, peters k, agho k, tannous wk. the effectiveness of patient-centred medical home-based models of care versus standard primary care in chronic disease management: a systematic review and meta-analysis of randomised and non-randomised controlled trials. int j environ res public health. 2020;17(18):6886. 22. mehta an, fenves az. hemodialysis adequacy: a review. dial transplant. 2010;39(1):20-2. 23. hojjat m. hemodialysis adequacy in patients with chronic renal failure. iran j crit care nurs. 2009;2(2):61-6. 24. zeraati a, mousavi ssb, mousavi mb. a review article: access recirculation among end stage renal disease patients undergoing maintenance hemodialysis. nephrourol mon. 2013;5(2):728. 25. gilmore j. kdoqi clinical practice guidelines and clinical practice recommendations–2006 updates. nephrol nurs j. 2006;33(5):487-9. 26. moist lm, hemmelgarn br, lok ce. relationship between blood flow in central venous catheters and hemodialysis adequacy. clin j am soc nephrol. 2006;1(5):965-71. 27. rezaiee o, shahgholian n, shahidi s. assessment of hemodialysis adequacy and its relationship with individual and personal factors. iran j nurs midwifery res. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e39 2016;21(6):577-82. 28. garland js, moist lm, lindsay rm. are hemodialysis access flow measurements by ultrasound dilution the standard of care for access surveillance? adv renal replace ther. 2002;9(2):91-8. 29. dias ts, neto mm, cardeal da costa ja. arteriovenous fistula puncture: an essential factor for hemodialysis efficiency. ren fail. 2008;30(9):870-6. 30. ozmen s, kadiroglu ak, ozmen ca, danis r, sit d, akin d, et al. does the direction of arterial needle in av fistula cannulation affect dialysis adequacy? clin nephrol. 2008;70(3):229-32. 31. reyes o. effects of arterial needle placement in arteriovenous fistula on dialysis adequacy of end-stage renal disease patients undergoing maintenance hemodialysis. j nurs healthc. 2016;1(2):1-10. 32. ozen n, aydin sayilan a, sayilan s, mut d, akin eb, ecder st. relationship between arteriovenous fistula cannulation practices and dialysis adequacy: a prospective, multicenter study. j ren care. 2022;48(1):41-8. 33. abasi m, lesanpezeshki m, asadi n. study of the relationship between vascular access types and recirculation in chronic hemodialysis. j ilam univ med sci. 2015;23(5):81-90. 34. parisotto mt, schoder vu, miriunis c, grassmann ah, scatizzi lp, kaufmann p, et al. cannulation technique influences arteriovenous fistula and graft survival. kidney int. 2014;86(4):790-7. 35. castro mcm, carlquist fty, silva cdf, xagoraris m, centeno jr, souza jacd. vascular access cannulation in hemodialysis patients: technical approach. j bras nefrol. 2019;42(1):38-46. 36. karkhah s, ghazanfari mj, emami zeydi a. what is the best between needles distance and direction for arteriovenous fistula cannulation in hemodialysis patients? an important yet challenging issue. j vasc access. 2021;23(3):490-1. 37. parisotto mt, pelliccia f, grassmann a, marcelli d. elements of dialysis nursing practice associated with successful cannulation: result of an international survey. j vasc access. 2017;18(2):114-9. 38. quicken s, huberts w, tordoir j, van loon m, delhaas t, mees b. computational modelling based recommendation on optimal dialysis needle positioning and dialysis flow in patients with arteriovenous grafts. eur j vasc endovasc surg. 2020;59(2):288-94. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references emergency. 2017; 5 (1): e55 br i e f re p o rt baseline characteristics of fall from height victims presenting to emergency department; a brief report hamidreza hatamabadi1, ali arhami dolatabadi2, batoul atighinasab3∗, saeed safari4 1. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, emdade shahid beheshti hospital, sabzevar university of medical sciences, sabzevar, iran. 4. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: december 2016; accepted: january 2017; published online: 31 january 2017 abstract: introduction: trauma due to accidents or fall from height is a major cause of disability and mortality. the present study was designed aiming to evaluate the baseline characteristics of fall from height victims presenting to emergency department (ed). methods: this prospective cross-sectional study evaluates the baseline characteristics of fall from height cases presenting to eds of three educational hospitals, tehran, iran, during one year. data were analyzed using spss 21 and presented using descriptive statistics. results: 460 patients with the mean age of 27.89 ± 20.95 years were evaluated (76.5% male). 191 (41.5%) falls occurred when working, 27 (5.9%) during play, and 242 (52.6%) in other times. among construction workers, 166 (81.4%) had not used any safety equipment. fracture and dislocation with 180 (39.1%) cases and soft tissue injury with 166 (36.1%) were the most common injuries inflicted. mean height of falling was 3.41 ± 0.34 (range: 0.5 – 20) meters. finally, 8 (1.7%) of the patients died (50% intentional) and 63% were discharged from ed. a significant correlation was detected between mortality and the falls being intentional (p < 0.0001) as well as greater height of fall (p < 0.0001). conclusion: based on the findings, most fall from height victims in the present study were young men, single, construction workers, with less than high school diploma education level. intentional fall and greater height of falling significantly correlated with mortality. keywords: accidental falls; multiple trauma; emergency service, hospital; population characteristics; patient outcome assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: hatamabadi h, arhami dolatabadi a, atighinasab b, safari s. baseline characteristics of fall from height victims presenting to emergency department; a brief report . 2017; 5(1): e55. 1. introduction t rauma due to accidents or fall from height is a major cause of disability and mortality among individuals aged less than 45 years in the united states of america, europe and third world countries (1). the cost of treatment and rehabilitation of these patients is estimated to be more than 33 billion dollars in the united states of america (2, 3). prevention is the most important solution for facing this phenomenon, which requires knowing the epidemiology of trauma (4-7). falling from height, happens at least once ∗corresponding author: batoul atighinasab; emergency department, emdade shahid beheshti hospital, sabzevar, razing avenue, sabzevar, iran. tel: 0098514464011520 ; email: ended@medsab.ac.ir. for about one third of housekeepers over 65 years old (8, 9). in a study by amani et al., fall from height was among the most common trauma mechanisms in their studied population with 38.5% prevalence (6). usually, the elderly are affected with this type of trauma following every-day activities and adults face it due to occupational accidents (10). in a study by zamani et al., evaluating hospitals of isfahan, fall from height was the second most common trauma mechanism after traffic accidents (7). fall from height has been the major cause of trauma related hospitalization for both male and female individuals in ireland (11). based on the statistics by the united states department of labor, approximately 150000 construction accidents happen annually. any injuries after falling can cause serious and permanent disabilities and increase the patient’s need for receiving treatment (12). falls this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com ended@medsab.ac.ir h. hatamabadi et al. 2 from more than 6 meters are usually counted as high-energy trauma and are referred to trauma centers (13). identifying the epidemiologic characteristics of fall from height victims can be beneficial in prevention and treatment of these patients. therefore, the present study was designed aiming to evaluate the baseline characteristics of fall from height victims presenting to emergency department (ed). 2. methods 2.1. study design and setting the present study is a prospective cross-sectional one that evaluates the baseline characteristics of fall from height cases in patients presenting to ed of imam hossein, shohadaye tajrish, and loghmane hakim hospitals, tehran, iran, from march 2012 to march 2013. protocol of the present study was approved by the ethics committee of shahid beheshti university of medical sciences and in agreement with the declaration of helsinki, the researchers adhered to protecting patients’ privacy and keeping their information confidential. informed consent form was signed by the patients before participating in the study. 2.2. participants census method was used for enrolling the participants and all victims of fall from height presenting to the 3 mentioned hospitals during one year were evaluated. no age or sex limitation was considered for this study. 2.3. data gathering by referring to the clinical profile and/or directly interviewing the patient or their relatives a checklist including demographic data (age, sex, marital status, occupation, level of education), route of transportation (ambulance or private vehicle), being intentional or unintentional, falling location (staircase, scaffold, rooftop, ladder), presence or absence of safety equipment, and outcome (discharge from ed, transfer to another hospital, admission to either surgery or neurosurgery ward, death) was filled for every patient. data were gathered by a senior emergency medicine resident under supervision of an emergency medicine specialist. 2.4. statistical analysis data were analyzed using spss statistical software version 21. for reporting quantitative variables mean ± standard deviation (sd) was used and for qualitative findings, frequency and percentage were described. chi-square or fisher’s exact tests were used for comparing qualitative variables and t-test was applied for comparing means. p < 0.05 was considered as significance level. 3. results: 3.1. demographic data 460 patients with the mean age of 27.89 ± 20.95 years (2 months – 94 years) were evaluated (76.5% male). 413 (89.8%) cases presented to imam hossein hospital, 26 (5.7%) to shohadaye tajrish hospital, and 21 (4.6%) to loghmane hakim hospital. table 1 shows the baseline characteristics of the patients. 191 (41.5%) falls occurred when working, 27 (5.9%) during play, and 242 (52.6%) in other times. mean time to ambulance arrival was 16.9 ± 9.26 minutes and mean time to reach hospital was 27.11 ± 16.7 minutes. among construction workers, 166 (81.4%) had not used any safety equipment. table 2 depicts clinical findings of the patients on arrival. fracture and dislocation with 180 (39.1%) cases and soft tissue injury with 166 (36.1%) were the most common injuries inflicted. mean height of falling was 3.41 ± 0.34 (range: 0.5 – 20) meters. table 1: baseline characteristics of studied patients age (year) < 18 150 (32.6) 18 60 246 (57.4) > 60 46 (10) sex male 352 (76.5) female 108 (23.5) marital status married 197 (42.8) single 263 (57.2) occupation construction worker 204 (44.3) housekeeper 55 (12) student 30 (6.5) others 171 (37.2) education level illiterate 229 (49.8) < diploma 159 (34.5) ≥ diploma 72 (15.7) route of transportation ambulance 195 (42.4) private vehicle 265 (57.6) intention intentional 13 (2.8) unintentional 447 (97.2) location staircase 122 (27.3) scaffold 94 (21) roof top 37 (8.3) ladder 36 (8.1) safety measures yes 422 (91.7) no 38 (8.3) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e55 table 2: clinical findings of studied patients when presenting to emergency department variable number (%) vital sign systolic blood pressure (mmhg) 111.4 ± 20.6 respiratory rate (/minute) 17.2 ± 4.8 pulse rate (/minute) 87.5 ± 15.3 o2 saturation (%) 95.4 ± 8.2 level of consciousness (gcs) 15 409 (88.8) 13-15 38 (8.3) 9-12 4 (0.9) 3-8 9 (2) location of injury head and face 198 (43.1) spinal column 85 (18.5) upper extremity 85 (18.5) lower extremity 50 (10.8) thorax 24 (5.2) abdomen and pelvic 18 (3.9) time of presentation morning (8 –14) 139 (30.2) evening (14 – 2) 295 (64) night (2 – 8) 27 (5.8) gcs: glasgow coma scale. table 3: emergency department outcome of studied patients variable number (%) vital sign discharge from ed 293 (63.7) admission to other wards 153 (33.3) transfer to other hospitals 6 (1.3) death 8 (1.7) ed: emergency department 3.2. outcome table 3 shows the ed outcome of the patients. finally, 8 (1.7%) of the patients died, 4 (50%) of which were intentional cases. mean height of falling was 6.77 ± 4.11 meters for intentional cases, which was significantly higher than unintentional accidents with the mean height of 3.23 ± 2.96 (p < 0.0001). a significant correlation was detected between mortality and the falls being intentional (p < 0.0001) as well as greater height of fall (p < 0.0001). 4. discussion based on the findings, most fall from height victims in the present study were young men, single, construction workers, with less than high school diploma education level who were presented to ed following fall from a staircase or scaffold. 63% of the patients were discharged from ed after receiving diagnostic and treatment services and reaching full recovery, while 1.7% of them died. intentional fall and greater height of falling significantly correlated with mortality. in a study by salimi et al. on 1141 trauma patients in ahwaz, 83.4% of the trauma patients were male (14). studies in ardabil and isfahan provinces also showed that about 70% of fall from height patients were male (6, 15). the reason for the high male to female ratio could be that construction workers are mostly men and they are more at risk of falling due to the type of their activity. in this study, 57.4% of the patients had a mean age of 27 years. in other words, most trauma patients were young individuals less than 30 years old, which is in line with findings of numerous other studies (6, 14, 15). in the current study, about 150 patients were under 18 years old. most children had falling accidents by falling from the arms of their parents or as a result of their neglect. therefore, by paying more attention and taking safety measures, these accidents can be prevented. similar to the results of zargar and amani, most participants of this study had education level of less than high school diploma and were construction workers (4, 6). in the amani et al. study, 29.3% of the patients were self-employed, 28.1% were unemployed , 17.3% were housekeepers, 10% had no job and 9.3 were construction workers (6). considering that our study only evaluated a specific type of trauma, it was expected to mostly include construction workers and housekeepers. the route of transportation to hospital was private vehicle in most cases and was ambulance in only 42%. in the study in isfahan, 49.6% of the patients were transported via ambulance, while in ahwaz only 11.8% of the patients were transported via an ambulance (14, 15). mean time of ambulance arriving and transportation to hospital were 16.9 and 27.11 minutes, respectively; which are similar to findings of zamani et al. study (15). head and face, spinal column and upper extremities were the most vulnerable body parts in this study, which is in line with the study by hatamabadi et al. (16). however, in the amani et al. study, head and face trauma was in second place after hands (6). in another study, head and face was in second place after extremities (15). outpatient treatment and discharge of trauma patients was reported to be more than 90% in zargar et al. study (4). in victims of traffic accident in abali road, outpatient treatment was more than 60%, hospitalization rate was 22.1%, rate of transfer to other hospitals was 1.5%, and discharge against medical advice was reported to be 16.1% (16). in another study, rate of discharge from ed was 49.3%, hospitalization in other wards was 43.2%, discharge against medical advice was 6.8% and death rate was reported as 0.7% (15). in total, fall from height is the second cause of trauma after traffic accidents in iran, which confirms that these accidents should be considered and evaluated more and preventive measures such as using helmet, safety belt, and gloves should be mandatory for construction workers. therefore, it is suggested to plan for further education and take more serious measures for these 2 types of trauma. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. hatamabadi et al. 4 4.1. limitations and suggestions since fall from height trauma patients were evaluated in 3 hospitals, namely imam hossein, shohadaye tajrish and loghmane hakim, it is possible that the participants do not fully represent the population of trauma patients in the society and it is suggested to carry out future studies in all hospitals around tehran or even iran. in addition, this study evaluates ed outcomes; therefore, the final outcome of the patients might be different than what has been reported. it is suggested to evaluate the outcome of the patients after discharge in a similar study. considering the fact that many of the construction workers in this study had not used proper safety equipment for working in heights, it is suggested to plan for further education and supervision in this area. 5. conclusion based on the findings, most fall from height victims in the present study were young men, single, construction workers, with less than high school diploma education level who were presented to ed following fall from a staircase or scaffold. intentional fall and greater height of falling significantly correlated with mortality. 6. appendix 6.1. acknowledgements this article is extracted from the thesis of dr. batoul atighinasab to earn his specialist degree in emergency medicine, registered in the research and technology department of shahid beheshti university of medical sciences. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding none. 6.4. conflict of interest none. references 1. jennett b. epidemiology of head injury. journal of neurology, neurosurgery & psychiatry. 1996;60(4):362-9. 2. ommaya ak, thibault l, bandak fa. mechanisms of impact head injury. international journal of impact engineering. 1994;15(4):535-60. 3. watson wl, ozanne-smith j. injury surveillance in victoria, australia: developing comprehensive injury incidence estimates. accident analysis & prevention. 2000;32(2):277-86. 4. zargar m, zafarghandi m, mdaghgh h, abasi k, rezai shirazi h. significance of trauma mechanism and its effect on the outcome of trauma patients. tehran university medical journal tums publications. 1998;56(5):101-8. 5. hatamabadi h, soori h, vafaee r, hadadi m, ainy e, asnaashari h. epidemiological pattern of road traffic injuries in tehran-abali axis in 2008: a prospective study. 2012. 6. amani f, habibzadeh s, rostami k. specifications of traumatized patients referring to fatemi hospital of ardabil, 2007-8. journal of ardabil university of medical sciences. 2009;9(1):13-22. . (full text in persian). 7. zamani m, esmailian m, mirazimi ms, ebrahimian m, golshani k. cause and final outcome of trauma in patients referred to the emergency department; a cross sectional study. iranian journal of emergency medicine. 2014;1(1):22-7. 8. lehtola s, koistinen p, luukinen h. falls and injurious falls late in home-dwelling life. archives of gerontology and geriatrics. 2006;42(2):217-24. 9. iida s, hassfeld s, reuther t, schweigert h-g, haag c, klein j, et al. maxillofacial fractures resulting from falls. journal of cranio-maxillofacial surgery. 2003;31(5):27883. 10. tinetti me, speechley m, ginter sf. risk factors for falls among elderly persons living in the community. new england journal of medicine. 1988;319(26):1701-7. 11. scallan e, staines a, fitzpatrick p, laffoy m, kelly a. injury in ireland. 2001. 12. tinetti me. prevention of falls and fall injuries in elderly persons: a research agenda. preventive medicine. 1994;23(5):756-62. 13. jeong by. occupational deaths and injuries in the construction industry. applied ergonomics. 1998;29(5):35560. 14. salimi j zm. an epidemiologic study of trauma patients admitted to the hospital ahwaz golestan. payesh quarterly. 2008;7(2):115-20. (full text in persian). 15. zamani m, esmailian m, mirazimi ms, ebrahimian m, golshani k. cause and final outcome of trauma in patients referred to the emergency department: a cross sectional study. iranian journal of emergency medicine. 2014;1(1):22-7. 16. hatamabadi h, vafaee r, haddadi m, abdalvand a, esna–ashari h, soori h. epidemiologic study of road traffic injuries by road user type characteristics and road environment in iran: a community-based approach. traf inj prev. 2012;13(1):61-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e4 or i g i n a l re s e a rc h level of self-care and patient care against covid-19 among emergency medical services personnel; a crosssectional study sirvan abbasi ghocham1, sina valiee2, naser kamyari3, salam vatandost2∗ 1. student research committee, kurdistan university of medical sciences, sanandaj, iran. 2. clinical care research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 3. department of biostatistics and epidemiology, school of health, abadan university ofmedical sciences, abadan, iran. received: october 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: provision of pre-hospital care by emergency medical services (ems) requires paying attention to self-care and patient care against possible infections. the present study was conducted with the aim of determining the level of self-care and patient care against covid-19. methods: the present correlational, descriptive, analytical study was carried out on 301 ems personnel in iran. data were collected using a demographic information form and questionnaires made by the researcher on the level of self-care and patient care against covid-19. results: the results showed that more than half of the participants (55%) were aged 27 to 34 years. the majority of the participants had an experience of participating in self-care (88.7%) and patient care (83.7%) training courses against covid-19. the overall score of self-care was 55.96 ± 6.97 out of 72 and that of patient care was 26.86± 3.39 out of 32, both of which revealed a favorable level. however, in some questions, the mean score was lower than the optimal level. the lowest mean score among items related to self-care against covid19 was allocated to wearing protective clothing (1.77±1.19). among items related to patient care against covid19, the lowest mean score was related to training the patient about hand hygine after touching contaminated equipment (2.83±1.08 out of 4). there was a positive (r=0.491) and significant correlation between self-care and patient care against covid-19 (p=0.001) based on our findings. conclusion: although the general level of selfcare and patient care against covid-19 was favorable, due to the undesired level of some domains, it seems necessary to implement corrective planning through periodical training and monitoring the performance of the personnel. keywords: covid-19; emergency medical services; infection control; patient care; self care cite this article as: abbasi ghocham s, valiee s, kamyari n, vatandost s. level of self-care and patient care against covid-19 among emergency medical services personnel; a cross-sectional study. arch acad emerg med. 2023; 11(1): e4. https://doi.org/10.22037/aaem.v11i1.1771. 1. introduction the outbreak of coronavirus disease 2019 (covid-19) caused an excessive increase in the workload of different groups of healthcare providers. one of these groups was emergency medical services (ems) personnel. ems personnel are one of the primary healthcare groups that have direct contact with all groups of patients. therefore, they are classified as frontline healthcare workers (1, 2). in iran, people ∗corresponding author: salam vatandost; kurdistan university of medical sciences campus, pasdaran blvd, sanandaj, iran. tel: +988783801405, fax: + 98 38380448, email: vatandost1366@gmail.com, orcid: https://orcid.org/ 0000-0003-4189-0954. who need immediate medical care call "115". based on the condition of the patients, they are either treated at the scene or transferred to medical centers (3). one of the important things in providing care to patients in each of the treatment groups is observing safe-care, which includes maintaining the health of personnel and preventing harm to the patient due to non-compliance with scientific and standard protocols. since covid-19 disease is highly contagious and has a notable incubation period and there is the possibility of the absence of evident symptoms in some patients, the possibility of transmission of this disease is high (4). adherence to infection control and protecting patients receiving services from ems for medical reasons other than covid-19 is important and can be considered as part of prothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. abbasi ghocham et al. 2 viding safe care to the patients (5). in addition to the general conditions mentioned, ems personnel are faced with various patients and numerous missions, emergency conditions, and limited time and equipment. therefore, the possibility of being infected with this virus is high among ems personnel. in addition to the contamination of personnel, if infection control standards are not followed, the risk of infecting non-covid-19 patients who need to receive medical services from ems personnel is high. in addition, the closed and limited space of the ambulance cabin and sharing medical equipment among patients are other predisposing factors, and failure to pay attention to infection control standards in this field also increases the risk of cross-infection between staff and patients (6). bledsoe et al., (2014) in america, showed that compliance with infection control standards among ems personnel was lower than the optimal level (7). in iran, mohammad khani et al., (2017) showed that the majority of ems personnel did not have good knowledge and performance regarding compliance with infection control standards (8). however, it has been found that compliance with standard precautions has a significant effect on reducing cross-infection between personnel and patients (9). the present study was conducted with the aim of determining the status of self-care and patient care for preventing the spread of covid-19 from the perspective of ems personnel. 2. methods 2.1. study design and settings the present correlational, descriptive, analytical study was carried out on emergency medical services (ems) personnel in kurdistan university of medical sciences iran, from january to march 2022. data was collected using a demographic information form and questionnaires made by the researcher on the level of self-care and patient care against covid-19. the present article was part of a master’s thesis approved by the school of nursing and midwifery and research and technology deputy of kurdistan university of medical sciences (ethics code: ir.muk.rec.1400.239). the patients were informed about the study objectives, informed consent was obtained from all the patients, and the patients were assured about the confidentiality of information they provided. 2.2. participants the study population included ems personnel working in urban and interurban medical emergency departments in emergency medical services (ems) affiliated to kurdistan university of medical sciences, iran. a total of 301 participants were included in the study. the inclusion criteria included willingness to participate in the study and the experience of providing care during covid-19 pandemic in medical emergencies. the exclusion criterion was not completing the questionnaires. 2.3. data gathering data collection was done by means of a demographic information form and a two-part researcher-made questionnaire on the level of compliance with self-care standards against covid-19 (section 1) and the level of compliance with patient care standards against covid-19 (section 2). section 1 included 18 questions. the questions were scored using a five-point likert scale ranging from 0 (never) to 4 (always). the total score was from 0 to 72. the results were reported as the mean score of each question (a score of 3 and above indicated a favorable level) and the total score of the questionnaire (a score of 50 and above indicated a favorable situation). the second section on the level of compliance with patient care standards against covid-19 included 8 questions. the questions were scored using a five-point likert scale ranging from 0 (never) to 4 (always). the range of scores was from 0 to 32. the results were reported as the mean score of each question (a score of 3 and above indicated a favorable situation) and the total score of the questionnaire (a score of 22 and above indicated a favorable situation). to perform psychometric evaluation of the questionnaires made by the researcher, the validity of each section was first tested using qualitative method (content validity and face validity) and experts’ opinions. qualitative evaluation of each section was carried out by another 10 new experts. the cvi (content validity index) was 0.85 and cvr (content validity ratio) was 0.81, indicating acceptable content validity. in addition, face validity was measured using a qualitative method, through receiving feedback from 30 ems personnel on the comprehensibility and clarity of the questions. cronbach’s alpha coefficient was used to measure the reliability of sections. cronbach’s alpha coefficient was 0.79, confirming the reliability of the sections. the participants were informed about the objectives of the study, and informed consent was obtained from each participant. the questionnaires were completed by the participants through self-report technique. 2.4. statistical analysis for the descriptive analysis of the data, frequency distribution (frequency and percentage), central tendency, and dispersion index (mean and standard deviation) were used. to do inferential analysis of data, kolmogorov-smirnov test was used to examine if data were normally distributed, and pearson’s correlation coefficient was used to check the possible relationship between mean scores. spss (version 26) was used for statistical analysis of data. a significance level of 0.05 was considered in all analyses. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e4 table 1: baseline characteristics of the participants (n=301) variables number (%) age (year) ≤26 68 (22.6) 34 – 27 166 (55.1) ≥35 67 (22.3) clinical work experience (year) ≤5 144 (47.8) 15 – 6 136 (45.2) ≥16 21 (7) education level associate degree 138 (45.8) bachelor’s degree 156 (51.8) master’s degree 7 (2.3) participation in infection control courses yes 197 (65.4) no 104 (34.6) getting covid-19 never 90 (29.9) once 146 (48.5) more than once 65 (21.6) receiving covid-19 vaccine no 10 (3.3) one dose 11 (3.7) two doses 168 (55.8) three doses 112 (37.2) receiving training related to self-care against covid-19 yes 267 (88.7) no 34 (11.3) receiving training related to patient care against covid-19 yes 252 (83.7) no 49 (16.3) 3. results 3.1. baseline characteristics of participants according to the findings, all the participants were male. 55.1% of the participants were in the 27 to 34 years age group. most of the participants had work experience less than 5 years. more than half of the participants had a bachelor’s degree (51.8%). about 96% of the participants had received covid-19 vaccine. the majority of the participants had a history of participating in infection control courses (65.4%) and received training on self-care (88.7%) and patient care (83.7%) against covid-19 (table 1). 3.2. level of self-care the total score of self-care against covid-19 was favorable (55.96±6.97out of 72). the results showed that 11 out of 18 items revealed a good condition (score greater than 3). the most favorable score was related to wearing a mask (3.95 ± 0.3 out of 4). seven items had a score lower than the desired level (less than 3). the lowest scores were allocated to wearing protective clothing (1.77±1.19 out of 4) and using face shield (1.86±1.35 out of 4) (table 2). 3.3. level of patient care the results indicated that the level of patient care against covid-19 was favorable (26.86±3.39 out of 32). out of 8 items, 7 had a favorable condition (score greater than 3), and the highest scores were related to the use of masks by personnel (3.69±0.62 out of 4) and use of nasal cannulas and face masks for the patients (3.68 ± 0.62 out of 4). according to table 3, the only unfavorable score was related to patient training about performing hand hygiene after touching contaminated equipment (2.83±1.08 out of 4). the results of the pearson correlation test showed a positive and significant correlation between the level of compliance with self-care standard and the level of compliance with patient care standard against covid-19 (r = 0.491, p = 0.001). 4. discussion the findings of present study showed that, general level of self-care and patient care against covid-9 was favorable, but level of some domains of self-care and patient care against covid-19, such as using protective clothing and face shields as measures related to self-care and training patients about hand hygine as measures related to patient care did were not at a good level. a significant number of the participants of the present study had an experience of participating in the infection control courses (65.4%). this statistic was higher than that revealed by wang et al., (2020) in china reporting 48% (11), martin et al., (2020) in latin america reporting 49% (12), and olsson et al., in sweden reporting 38% (13). the reason for this difference, in addition to the professional motives of people to increase their awareness in the field of infection control, can be the influential impact of participating in in-service courses and provision of relevant documentation in the annual evaluation and promotion of ems personnel in iran. the current study showed that 70% of the personnel were infected with covid-19 at least once, which was a high number. although no accurate reports on the rate of infection among ems personnel in other countries were found, it was significantly higher in our study compared to the infection rate of other groups of healthcare workers (hcws). for instance, it was 19% in ethiopia, 20% in italy and in the united states, and 15% in spain according to a study done by atnafie et al (14). given the acceptable overall score of self-care against covid-19, the reasons justifying the higher prevalence of infection compared to other health treatment groups can be emergency working conditions and time limit to fully protect oneself before close contact with patients. due to the time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. abbasi ghocham et al. 4 table 2: the level of self-care against covid-19 item mean sd 1. do you wear protective clothing that is resistant to the penetration of secretions when caring for a patient suspected of covid-19? 1.77 1.19 2. do you use gloves when caring for a patient suspected of covid-19? 3.74 0.65 3. do you use a face shield when caring for a suspected patient? 1.86 1.35 4. do you use a mask when caring for a suspected patient? 3.95 0.30 5. do you examine the patient for signs of fever, cough, and shortness of breath to prevent possible transmission of covid-19? 3.74 0.61 6. do you touch your face during the mission? 2.58 1.37 7. do you adhere to hand hygiene after the mission? 3.82 0.59 8. do you avoid unnecessary contact with patients? 3.61 0.62 9. on missions, if you wear protective clothing, do you take off your personal protective clothing before getting back to the ambulance and start transferring the patient? 2.38 1.43 10. on missions, do you take off your gloves before starting to drive the ambulance and transport the patient? 3.11 1.14 11. do you let the patient’s companions to get into the ambulance cabin? 2.70 1.13 12. do you turn on the patient’s cabin ventilation fan during patient transfer? 3.23 0.95 13. do you leave the rear doors of the ambulance open after completing the mission? 2.86 1.17 14. do you put clothes and personal protective equipment in an infected trash can after completing the mission? 3.64 0.73 15. do you care about the patient’s companion wearing a mask? 3.58 0.73 16. before going on a mission, are you informed if the patient is suspected to have covid-19 infection or about the possible risk of transferring the patient by the dispatch control center? 2.76 0.96 17. do you give a bag to a patient who has nausea and vomiting to prevent infection? 3.59 0.67 18. do you minimize airway interventions that may cause coughing (e.g. suctioning)? 3.03 1.02 total 55.96 6.97 sd: standard deviation. table 3: the level of patient care against covid-19 item mean sd 1. in the absence of any restrictions, do you use a facemask for the patient? 3.29 0.84 2. do you adhere to hand hygiene before starting to care for a patient? 3.30 0.86 3. do you use disposable care equipment if you need care equipment such as oxygen mask and nasal catheter? 3.68 0.62 4. do you disinfect equipment between missions? 3.37 0.82 5. do you minimize your contact with the patient to prevent possible infection? 3.39 0.69 6. do you consider not exposing the patient to unprotected staff, patients, and companions to prevent the patient from becoming infected? 3.30 0.72 7. do you use a facemask when providing care for the patient to prevent the transmission of possible infection to the patient? 3.69 0.62 8. do you train the patient about hand disinfection after touching infected equipment? 2.83 1.08 total 26.86 3.39 sd: standard deviation. constraints and the stress of the companions while reaching the patient’s bedside, one of the important measures to manage the health of personnel can be doing the preparations on the way to the mission and before coming into contact with patients. the overall results showed the good state of self-care against covid-19, which was in line with a study by zhang et al., (2021) on healthcare workers in china (15). however, the aforementioned study was conducted on all healthcare workers. comparing the results of studies done before the covid19 pandemic with those of current study regarding self-care against the infectious agent, it can be found that self-care was at an unfavorable level among ems personnel before the pandemic (7, 8, 16). this difference can be caused by the feeling of less danger by the personnel in the non-epidemic situation compared to epidemic one. nevertheless, self-care against infectious agents should be considered according to the working conditions of the personnel. it should be noted that providing medical services to infectious patients, especially those without obvious clinical symptoms, in nonepidemic conditions is possible although less likely. therefore, considering the importance of personnel’s health, reducing days away from work, and providing better quality services, it is necessary that the issue of self-care against facthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e4 tors that threaten the health of ems personnel be considered by personnel and evaluated by superiors even after the normalization of the covid-19 epidemic. in separate examination of each of the questions related to self-care against covid-19, the results of the present study showed that the mean score of the item related to wearing protective clothing when caring for a patient suspected of covid-19 was at an unfavorable level, which was in line with the results of a study done by lai et al., (2020) on hcws in china (17). however, tabah et al., (2020) in their study on australian hcws showed a favorable situation in this regard (18). lack of using protective clothing resistant to penetration of secretions can be due to the personnel’s low knowledge and negative attitude about this issue, the limited access due to the high demand for the use of protective equipment during the covid-19 pandemic, and unwillingness to use this clothing due to warm environments. the findings of this study also indicated that the mean score of the item related to wearing a face shield when caring for a patient suspected of covid-19 was at an unfavorable level, which was consistent with the results of studies done by zhang et al., (2021) (15) and lai et al. (2020) on hcws in china (17). in contrast, tabah et al., (2020) on australian hcws (18) reported a favorable condition in this regard. considering that the main route of transmission of respiratory diseases, including covid-19, is through the organs of the head and face (mouth, nose, and eyes) and the close contact of the personnel with the patient, the use of face shield is important to reduce the spread of infection. the results on the mean score of touching the head and face revealed unfavorable level, which was in line with the results of the study done by wang (11). since most of the patients receiving medical services have acute conditions, one of the obstacles against complying with infection control standards is time limit. therefore, not disinfecting or washing hands before touching the face can be associated with the risk of infection transmission, and it can be considered as one of the causes of high incidence of covid-19 in the present study. the mean score of the item related to taking off protective equipment after completing the mission and before getting into the ambulance showed an unfavorable condition. however, related studies emphasized the removing of used equipment after completing the mission (19-21). not removing contaminated clothes after completing the mission, in addition to the possibility of contaminating the ambulance driver’s cabin, can increase the risk of infection transmission to other personnel. the results indicated that compliance with opening the ambulance door after completing the mission was low. however, based on the protocols for decontamination of the ambulance environment, establishing proper ventilation, and disinfecting the environment inside the rear cabin after completing the mission and before starting the next mission is necessary to reduce the risk of infection transmission to personnel or other patients (22). considering aerosol production by patients infected with covid-19 and given that covid-19 virus is primarily transmitted between people through respiratory droplets, it is more important to observe this item. in the present study, the mean score related to being informed about suspition to or definitive infection and the possible risks of transferring the patient by the dispatch control center was less than the optimal level. however, studies showed that for the safe transfer of patients with suspected infection, reducing the risk of disease transmission during medical rescue operations at the scene and during patient transfer, and the information collected by the emergency dispatcher is of key importance (23). having previous information about the patient before dispatching is vital for a more successful mission for the patient and the personnel (24). on the other hand, given the spread of covid19 and the possibility that patients infected with this disease may ask for medical services due to other medical problems, it is necessary to obtain and pay attention to information about possible symptoms of communicable infectious diseases, such as covid-19, to take self-protection measures more seriously. the results indicated that the overall condition of patient care against covid-19 was favorable. however, only the mean score of the item related to training the patient about hand hygiene after touching contaminated equipment was lower than the desired level. hand hygiene is one of the most important aspects of controlling various infections, including covid-19 (25). however, patients, due to different reasons such as lack of awareness about hand hygiene control, lack of information about potential contamination of ambulance equipment and environment, or emergency situation, do not pay much attention to hand hygiene during their transfer to the hospital. therefore, lack of training and reminding patients increases the risk of getting infected. the results also indicated a positive and significant correlation between the level of self-care and patient care against covid-19. hence, it can be concluded that people who follow infection control protocols play an important role in reducing the transmission of infection to themselves and the patient, subsequently reducing the spread of the disease in general. similarly, gulsen et al., in their study done in turkey, showed that ems personnel who used a protective mask for the patients were at a lower risk of getting covid-19 (26). 5. limitation considering that the samples are limited to one province, it is necessary to conduct a study in a larger research environthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s. abbasi ghocham et al. 6 ment in order to obtain more comprehensive information. on the other hand, it is necessary to pay attention to the time of conducting the study, which was during the outbreak of covid-19, because the infection control status may be under the influence of this epidemic situation. further studies are needed in order to confirm these findings. 6. conclusion based on the results of this study, some aspects related to self-care and patient care were not at a desirable level, although the general status of self-care and patient care against covid-19 was favorable. therefore, it is necessary to pay attention to reform programs such as infection control training in university studies, in-service training courses, monitoring the performance of personnel through field observations, and praising people who comply with infection control standards. 7. declarations 7.1. acknowledgments the present study was extracted from a master’s thesis approved by the research deputy of kurdistan university of medical sciences (ir.muk.rec.1400.239). we would like to express our gratitude to the officials of the university’s research deputy and all the study participants who cooperated with us in conducting this research. 7.2. conflict of interest the authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. 7.3. fundings and supports this work was financially supported by the vice-chancellor for research and technology affiliated with kurdistan university of medical sciences, iran. 7.4. authors’ contribution study design: salam vatandost, sina valiee, and naser kamyari. data collection: sirvan abbasi data analysis: naser kamyari and salam vatandost. study supervision: salam vaandost. manuscript writing: sina valiee, sirvan abbasi, and salam vatandost. critical revisions for important intellectual content: sina valiee, sirvan abbasi, naser kamyari and salam vatandost. references 1. nohl a, afflerbach c, lurz c, brune b, ohmann t, weichert v, et al. acceptance of covid-19 vaccination among front-line health care workers: a nationwide survey of emergency medical services personnel from germany. vaccines (basel). 2021;9(5):1-12. 2. pereira er, 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a crosssectional study in brazil, colombia, and ecuador. plos one. 2020;15(11): doi: 10.1371/journal.pone.0242185. 13. olsson h, olsson s, sturesson l, lindström v. do we need this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e4 a pandemic to improve hygiene routines in the ambulance service? a cross-sectional study. int emerg nurs. 2022;62: https://doi.org/10.1016/j.ienj.2022.101171. 14. atnafie sa, anteneh da, yimenu dk, kifle zd. assessment of exposure risks to covid-19 among frontline health care workers in amhara region, ethiopia: a cross-sectional survey. plos one. 2021;16(4): https://doi.org/10.1371/journal.pone.0251000 15. zhang yg, shen l, zhang sj, wang hz, zhang xh, huang yg. 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[available from: https://www.cdc.gov/coronavirus/2019ncov/hcp/guidance-for-ems.html]. 22. lindsley wg, blachere fm, mcclelland tl, neu dt, mnatsakanova a, martin sb, jr., et al. efficacy of an ambulance ventilation system in reducing ems worker exposure to airborne particles from a patient cough aerosol simulator. j occup environ hyg. 2019;16(12):804-16. 23. mikos m, dymura k, gałązkowski r, rzońca p, żurowskawolak m. transport safety concerning a patient infected with sars-cov-2 and emergency service officers in an ambulance accident a case study. disaster med public health prep. 2022:1-10. 24. medcalf ds. alhallaf m, "planning and facilitating the training of emergency medical services on the safe transport of patients with highly infectious diseases" (2020). theses & dissertations. 437. spring 5-9-2020. 25. mouajou v, adams k, delisle g, quach c. hand hygiene compliance in the prevention of hospital-acquired infections: a systematic review. j hosp infect. 2022;119:33-48. 26. gulsen mf, kurt m, kaleli i, ulasti a. personal protective equipment (ppe) using in antalya 112 emergency ambulance services during outbreak. medrxiv. 2020 jan 1. theses & dissertations. doi: 10.24966/ets-8798/s1002. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e86 or i g i n a l re s e a rc h predictors of postoperative outcome in emergency laparotomy for perforation peritonitis; a retrospective cross-sectional study ankit rai1, farhanul huda1∗, praveen kumar2, lena elizabath david1, chezhian s1, somprakas basu1, sudhir singh1 1. department of general surgery, all india institute of medical sciences, rishikesh, india. 2. department of surgery, himalayan institute of medical sciences, dehradun, india. received: august 2022; accepted: september 2022; published online: 31 october 2022 abstract: introduction: hollow viscus perforation is a significant cause of surgical mortality. various attempts have been made to identify high-risk patients preoperatively and optimize and manage such patients more aggressively. this study aimed to evaluate the predictors of outcome in patients undergoing emergency laparotomy for perforation peritonitis. methods: this retrospective cross-sectional study was conducted on perforation peritonitis cases admitted to the department of general surgery, all india institute of medical sciences, rishikesh, india. the association between preoperative patient variables with postoperative complications, anastomotic leaks, need for intensive care unit (icu) admission, and 30-day mortality were evaluated. results: tachycardia at the time of admission (t = 2.443, p = 0.020), hypotension (χ2 = 18.214, p = <0.001), lower haemoglobin (t = -4.134, p = <0.001), higher blood urea nitrogen levels (w = 1967.000, p = 0.012), international normalised ratio (inr) ≥ 1.5 (χ2 = 17.340, p = <0.001), the mean albumin level 2.89 ± 0.77 g/dl (t = -2.348, p = 0.027), and delay in surgery (χ2 = 28.423, p = 0.008) were significant associate factors of mortality. the association between need for icu admission and higher pulse rate on admission (w = 2782.500, p = 0.011), lower systolic blood pressure (w = 1627.500, p = 0.029), higher blood urea nitrogen (w = 2299.000, p = 0.030) and serum creatinine levels (w = 2192.500, p = 0.045), preoperative coagulopathy (χ2 = 6.773, p = 0.017), hypoalbuminemia (t = -2.515, p = 0.016), and delay in surgery (χ2 = 17.780, p = 0.016) was significant. conclusion: based on the results of this study, hypotension, azotaemia, coagulopathy, and delay in surgery, increase the risk of postoperative mortality of patients undergoing emergency laparotomy for perforation peritonitis. tachycardia, hypotension, azotaemia, hypoalbuminemia, and pre-operative coagulopathy were good predictors of need for icu admission. shock at presentation, deranged renal function and coagulopathy were associated with an increased risk of postoperative complications. keywords: emergencies; intestinal perforation; mortality; peritonitis cite this article as: rai a, huda f, kumar p, david le, chezhian s, basu s, singh s. predictors of postoperative outcome in emergency laparotomy for perforation peritonitis; a retrospective cross-sectional study. arch acad emerg med. 2022; 10(1): e86. https://doi.org/10.22037/aaem.v10i1.1827. 1. introduction gastrointestinal tract perforation is one of the most common surgical emergencies worldwide. peritonitis and the resultant sepsis and systemic complications due to the perfo∗corresponding author: farhanul huda, department of general surgery, all india institute of medical sciences, rishikesh, uttarakhand-249203, india. email: farhanul1973huda@gmail.com, tel: +91-9997533211, orcid: https://orcid.org/0000-0002-1309-1832. ration are still responsible for significant mortality despite the advent of newer antibiotics, safer operative and anaesthetic techniques, and an improved understanding of preand postoperative management (1). rapid source control through surgical exploration and prudent antimicrobial therapy is fundamental for treating intra-abdominal sepsis due to perforation (2). billing et al. proposed early prognostic assessment of patients with perforation peritonitis to allow triaging of patients for a more aggressive therapeutic approach (3). several scoring systems have since been developed to enable general and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 2 prognostic evaluation of patients with perforation peritonitis (2, 4). bohen et al. did an anatomical classification of intraabdominal infections into three groups (group iappendicitis and perforated duodenal ulcer; group iiperitonitis from all other intra-abdominal organs, not following surgery; and group iiipostoperative peritonitis) and showed a difference in outcomes between them (4). the acute physiology and chronic health evaluation (apache) system, on the other hand, is a non-specific physiologic scoring system that has been validated for risk stratification and has also been used in several studies for intra-abdominal infections (5). meakins and associates proposed an approach for the study and clinical management of intra-abdominal infections that combined functional and anatomical components (6). singh et al. did a prospective analysis of 84 patients with perforation peritonitis and identified laboratory indices, delay in presentation, and surgery as good predictors of postoperative mortality (7). most of these scoring systems are exhaustive and challenging to use in emergency departments. this study aimed to evaluate the predictive factors of postoperative outcome in patients undergoing emergency laparotomy for perforation peritonitis. 2. methods 2.1. study design and settings a retrospective cross-sectional study was conducted in the department of general surgery at the all india institute of medical sciences, rishikesh, a government-run medical university and tertiary-care hospital in northern india. the study period was from 01st july 2017 to 01st july 2020. the association between preoperative patient variables with postoperative complications, anastomotic leaks, need for intensive care unit (icu) admission, and mortality were studied. approval was obtained from the institute’s ethics committee before the study (aiims/iec/20/741). the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (tripod) statement was adhered to while reporting this study (8). 2.2. participants all adult patients admitted to general surgery department with the diagnosis of peritonitis due to perforation of the gastrointestinal (gi) tract were included on the basis of clinical findings, pneumoperitoneum on chest x-ray, or abdominal computed tomography (ct). all cases of primary peritonitis, perforations due to corrosive intake, trauma, postoperative peritonitis due to anastomosis leakage, pregnant patients, and patients whose records were not available were excluded. 2.3. data collection patient data were retrospectively collected from the electronic health records (ehr) of the hospital database. patient details such as demographic information (age, gender, co-morbidities/addictions), symptoms at the time of presentation (pain abdomen, vomiting, fever, ileus), vital signs at the time of presentation (heart rate, blood pressure), and preoperative blood parameters (haemoglobin, total leucocyte count, serum creatinine, blood urea, international normalised ratio (inr), serum albumin) were collected. the type of management (operative/non-operative), delay in surgery, and the anatomical site of perforation were also recorded. 2.4. outcomes postoperatively, data regarding complications (using the clavein-dindo classification)(9), anastomotic leaks, need for icu admission, and 30-day postoperative mortality were collected. 2.5. statistical analysis the sample size was based on a study by jhobta et al., who reported 10% mortality in patients with perforation peritonitis (10). it was calculated according to the formula by lemeshow et al., (11). with a precision (δ) of 0.05 (5%), and type i error (α) at 0.05 (5%), z was taken as 1.96. based on the above formula, the required sample size was calculated as, n = [1.962 x 0.10 x (1-0.10)] / 0.052 = 138.29 ≈ 139. thus, with a 95% confidence interval, the minimum sample size required for the study was 139. statistical analysis was done using the spss statistics package v23 (ibm corp., usa)(12). we tried to explore the association between the preoperative patient variables with the postoperative outcomes, as mentioned above. group comparisons for continuously distributed data were made using the independent sample t-test. for non-normally distributed data, an appropriate non-parametric test, such as the wilcoxon test, was used. chi-squared test was used for group comparisons of categorical data. in case the expected frequency in the contingency tables was found to be <5 for >25% of the cells, fisher’s exact test was used instead. linear correlation between the variables was explored using pearson’s and spearman’s correlation for normally and non-normally distributed data, respectively. statistical significance was kept at p<0.05. 3. results 3.1. baseline characteristics of studied cases one hundred eighty-three consecutive cases of perforation peritonitis with the mean age of 42.61 ± 15.99 (range: 18-85) years presenting during our study period were included in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e86 the study (80.5% male). 13% of patients had some comorbidity such as diabetes mellitus, hypertension, tuberculosis, etc. most of the patients also had some form of addiction, with smoking (52.4%), and alcohol intake (20.5%) being common. 3.2. associated factors of outcomes i. postoperative anastomotic leaks participants in the age group 41-50 years had the highest proportion of leaks (χ2 = 16.846, p = 0.026). among the presenting symptoms, ileus was significantly associated with anastomotic leaks (χ2 = 4.941, p = 0.043). the site of perforation was also associated with postoperative leaks (χ2 = 41.051, p = 0.045), with duodenum, caecum or ascending colon perforations contributing to the majority of leaks. table 1 shows the associated factors of postoperative anastomotic leak of studied cases. ii. postoperative complications vomiting as a presenting complaint was a predictor of postoperative complications (p = 0.005). the duration of ileus at presentation also predicted delayed complications (p = 0.027). shock (systolic blood pressure (sbp) < 100 mmhg) on admission correlated with poor prognosis (p = 0.013). among the blood parameters, raised serum creatinine (p = 0.043) and coagulopathy (inr > 1.5) (p = 0.017) predicted postoperative complications. table 2 shows the association between different grades of clavien-dindo postoperative complications (9) and preoperative variables. iii. icu admission table 3 summarizes the association between need for icu admission and preoperative parameters. patients who required icu admission had a higher pulse rate on admission (w = 2782.500, p = 0.011). the median (interquartile range; iqr) of systolic bp in the icu admission group was 103 (90120) mmhg. there was a significant difference in systolic bp (w = 1627.500, p = 0.029) between groups, with the median systolic bp being highest in the group that did not require icu admission. subgroup analysis revealed a significant difference between the groups, sbp < 100 and sbp ≥ 100 (χ2 = 12.194, p = <0.001). deranged renal function was significantly associated with icu admission, with both blood urea (w = 2299.000, p = 0.030) and serum creatinine levels significantly elevated (w = 2192.500, p = 0.045). preoperative coagulopathy also predicted icu admission (χ2 = 6.773, p = 0.017). hypoalbuminemia was also a strong predictor of icu admission (t = -2.515, p = 0.016), with 2.17 times higher chance of admission in those with albumin <2.5g/dl (95% ci= 0.79-5.94). the reason for delay in surgery was also a significant predictor of icu admission (χ2 = 17.780, p = 0.016). iv. postoperative mortality table 4 summarizes the association between 30-day mortality and preoperative parameters. tachycardia at the time of admission was associated with higher postoperative mortality (t = 2.443, p = 0.020). however, on subgroup analysis, no difference was observed between the groups, pulse rate (pr) < 100 and pr ≥ 100 (χ2 = 3.722, p = 0.054). hypotension was also associated with increased postoperative mortality (χ2 = 18.214, p = <0.001) with 4.55 times higher risk of mortality in the group with systolic bp ≤ 100 mmhg (95% ci = 2.19 9.22). diastolic bp was also significantly associated with postoperative mortality (w = 988.500, p = <0.001). the haemoglobin (hb) in the postoperative mortality group was significantly lower (t = -4.134, p = <0.001). however, no difference in the group hb ≤ 8 g/dl and hb > 8g/dl (χ2 = 4.925, p = 0.061) was evident on subgroup analysis. on the other hand, blood urea levels influenced postoperative mortality (w = 1967.000, p = 0.012). inr ≥ 1.5 was also associated with higher mortality (χ2 = 17.340, p = <0.001). the mean (standard deviation; sd) of albumin level in mortality group was 2.89 (0.77) g/dl and was significantly associated with postoperative mortality (t = -2.348, p = 0.027). no difference was evident on subgroup analysis between the groups, albumin ≤ 2.5 g/dl and > 2.5 g/dl (χ2 = 3.685, p = 0.089). there was a significant difference in mortality due to surgery delay (χ2 = 28.423, p = 0.008). delay due to initial resuscitation led to the highest rate of mortality. 4. discussion based on the results of this study, hypotension, azotaemia, coagulopathy, and delay in surgery increase the risk of postoperative mortality of patients undergoing emergency laparotomy for perforation peritonitis. tachycardia, hypotension, azotemia, hypoalbuminemia, and preoperative coagulopathy were good predictors of icu admission. shock at presentation, deranged renal function and coagulopathy were associated with an increased risk of postoperative complications. generalised peritonitis is a common surgical emergency. it is one of the leading causes of death in non-trauma surgical patients, with a mortality as high as 20% (2, 3). even with the advancement in diagnostic and therapeutic aspects over the years, a significant number of lives are being lost to this illness. several modifiable and non-modifiable factors can influence the clinical outcome in patients with perforation peritonitis. attempts must be made to identify and optimize the highrisk patient preoperatively, while simultaneously preparing for emergency surgery. multiple studies have tried to identify the factors that can influence the clinical outcome in these patients. certain factors and lab parameters can be used to predict the outcome, and several scoring systems have been devised using them, such as the acute physiology and chronic health evaluation (apache) score, the simplified acute physiology score (saps), the boey score, the multithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 4 organ failure (mof) score, and the mannheim peritonitis index (mpi) (2, 7). these scores are not simple to use and are time-consuming. preoperative functional status is also being used for predicting the postoperative outcome (13). it is, thus, more relevant to identify simple patient parameters that can predict postoperative complications and mortality. anastomotic leak is one of the major complications following bowel repair or anastomosis. the uk surgical infection study group defined an enteric leak as "leakage of luminal contents from a surgical join between two hollow viscera" (14). several factors have been linked to anastomotic leaks such as, malnutrition, steroids, tobacco use, leukocytosis, cardiovascular disease, alcohol use, lower gi anastomoses, suboptimal anastomotic blood supply, operative time of more than 2 hours, bowel obstruction, perioperative blood transfusion, and intra-operative septic conditions not conducive to a primary anastomosis (15, 16). we report the highest rate of anastomotic leaks between 41-50 years of age (χ2 = 16.846, p = 0.026). mcdermott et al. found that the mean age group was 60 years and that age did not correlate with postoperative leakage (17). we found preoperative ileus to be significantly associated with anastomotic leaks (χ2 = 4.941, p = 0.043). peter et al. observed similar findings in patients undergoing colorectal resection (15). multiple studies have shown that those with lower gi anastomoses are more prone to leaks than those having anastomoses in the upper gi tract, especially after emergency surgery (16, 18). we found the site of perforation to be associated with anastomotic leaks (χ2 = 41.051, p = 0.045). however, most leaks in our patients occurred following duodenal, caecal, and colonic perforations, in that order. in another study, gupta et al. observed that the size of the duodenal perforation determines the risk of postoperative leak (19). we report hypotension at the time of admission as an important predictor of postoperative mortality (χ2 = 18.214, p = 0.001) with 4.55 times higher risk in those with systolic bp ≤ 100 mmhg (95% ci = 2.19 9.22). diastolic bp was also significantly associated with postoperative mortality (w = 988.500, p =0.001). singh et al. also found that shock could predict poor postoperative outcomes, which is in line with our findings (7). in a study by wesselink et al., the authors observed that intraoperative mean arterial pressure (map) less than 60-65mm hg was associated with poor surgical outcomes (20). we conclude that deranged renal function and hypoalbuminemia are important predictors of postoperative complications. this is in concordance with studies conducted previously (3, 21). presence of coagulopathy (inr >5) was also related to postoperative mortality (t = -2.348, p = 0.027). this could be a result of sepsis-induced disseminated intravascular coagulopathy (dic). in a single-centre analysis, nakamura et al. found that preoperative dic score is a prognostic factor for colonic perforation associated with peritonitis (22). moreover, patients with deranged kidney function, hypoalbuminemia, and deranged inr were more likely to require icu admission post-surgery. however, the other important causes of raised creatinine in these patients, such as urinary tract obstruction (stones, neoplasms, prostatic hyperplasia), diabetes, and nephrotoxic drug intake, must also be kept in mind. it seems that preoperative variables such as tachycardia, hypotension, deranged renal function, coagulopathy, and hypoalbuminemia are strong predictors of poor prognosis in patients with perforation peritonitis. identifying one or more of these high-risk predictors calls for a more aggressive resuscitation with rapid source control for a favourable patient outcome. 5. limitation this study was a retrospective one, and data collection was record-based. a larger prospective study is, thus, required to generate more substantial evidence. this study was conducted at a tertiary-care referral centre, thus receiving the sickest patients from the state and outside. moreover, there was a significant delay in the presentation of patients due to the arduous himalayan terrain. all of these could potentially cause a systematic error in favour of the most critical patients, which may not be the case at other centres, and thus, result in an overestimation in our findings. age, and pre-existing systemic illnesses, are specific confounders that must also be individually matched for to generate more decisive evidence. the role of inflammatory markers such as c-reactive protein and procalcitonin in severity assessment in patients with perforation peritonitis and abdominal sepsis is well known (23, 24). however, due to the high costs of these tests and non-affordability by the majority of our patients, they could not be included in the present study. 6. conclusion based on the results of this study, hypotension, azotaemia, coagulopathy, and delay in surgery increase the risk of postoperative mortality of patients undergoing emergency laparotomy for perforation peritonitis. tachycardia, hypotension, azotaemia, hypoalbuminemia, and pre-operative coagulopathy were good predictors of icu admission. shock at presentation, deranged renal function, and coagulopathy were associated with an increased risk of postoperative complications. 7. declarations 7.1. acknowledgments we acknowledge the support of faculty and residents of the department of general surgery, all india institute of medical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e86 sciences, rishikesh (india). 7.2. funding and support nil. 7.3. conflict of interest the authors declare that they have no conflict of interest. 7.4. authors’ contribution dr. somprakas basu, dr. farhanul huda, dr. praveen kumar conceptualised the study; dr. ankit rai, dr. lena elizabath david, dr. chezhian s did the data collection; dr. ankit rai, and dr. lena elizabath david did the data analysis; dr. ankit rai, dr. lena elizabath david, dr. chezhian s prepared the first manuscript; dr. somprakas basu, dr. farhanul huda, dr. sudhir singh, dr. praveen kumar, dr. ankit rai, dr. lena elizabath david, dr. chezhian s reviewed the manuscript; dr. somprakas basu, dr. farhanul huda, dr. praveen kumar supervised the study at all stages. 7.5. data availability the data used and/or analyzed in the study are available with the corresponding author and can be provided on request. 7.6. ethical considerations this study was approved by the institute ethics committee of the all india institute of medical sciences, rishikesh (aiims/iec/20/741). the committee waived patient consent for this study as medical records were used for data collection and a statement on patient data confidentiality and compliance with the declaration of helsinki was provided. references 1. meshram s, lal m. 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ibm spss statistics for windows. 23 ed. armonk, new york: ibm corp.; 2015. 13. leung jm, dzankic s. relative importance of preoperative health status versus intraoperative factors in predicting postoperative adverse outcomes in geriatric surgical patients. j am geriatr soc. 2001;49(8):1080-5. 14. langell jt, mulvihill sj. gastrointestinal perforation and the acute abdomen. med clin north am. 2008;92(3):599625, viii-ix. 15. peters eg, dekkers m, van leeuwen-hilbers fw, daams f, hulsewé kwe, de jonge wj, et al. relation between postoperative ileus and anastomotic leakage after colorectal resection: a post hoc analysis of a prospective randomized controlled trial. colorectal dis. 2017;19(7):667-74. 16. calin md, bălălău c, popa f, voiculescu s, scăunas, u rv. colic anastomotic leakage risk factors. j med life. 2013;6(4):420-3. 17. mcdermott fd, heeney a, kelly me, steele rj, carlson gl, winter dc. systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. br j surg. 2015;102(5):462-79. 18. oheneh-yeboah m. postoperative complications after surgery for typhoid ileal perforation in adults in kumasi. west afr j med. 2007;26(1):32-6. 19. gupta s, kaushik r, sharma r, attri a. the management of large perforations of duodenal ulcers. bmc surgery. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 6 2005;5(1):15. 20. wesselink em, kappen th, torn hm, slooter ajc, van klei wa. intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. br j anaesth. 2018;121(4):706-21. 21. doklestić sk, bajec dd, djukić rv, bumbaširević v, detanac ad, detanac sd, et al. secondary peritonitis evaluation of 204 cases and literature review. j med life. 2014;7(2):132-8. 22. nakamura f, yui r, muratsu a, sakuramoto k, muroya t, ikegawa h, et al. study of the prognostic factor of the colon perforation case with the pan-peritonitis that needed emergency surgery: a single-center observational study. acute med surg. 2019;6(4):379-84. 23. mulari k, leppäniemi a. severe secondary peritonitis following gastrointestinal tract perforation. scand j surg. 2004;93(3):204-8. 24. reith hb, mittelkötter u, wagner r, thiede a. procalcitonin (pct) in patients with abdominal sepsis. intensive care med. 2000;26 (suppl 2):s165-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e86 table 1: associated factors of postoperative anastomotic leak in the studied patients parameters anastomotic leak p present (n = 7) absent (n = 178) age ( years) mean ± sd 50.14 ± 6.31 42.31 ± 16.19 0.133 41-50 years 5 (14.7) 29 (85.3) 0.026 51-60 years 2 (7.1) 26 (92.9) gender male 7 (4.7) 142 (95.3) 0.349 female 0 (0.0) 36 (100.0) co-morbidities addiction 6 (4.9) 116 (95.1) 0.426 symptoms pain 7 (3.8) 176 (96.2) 1.000 vomiting 3 (3.4) 85 (96.6) 1.000 fever 4 (8.5) 43 (91.5) 0.073 ileus 7 (6.4) 102 (93.6) 0.043 duration of symptoms (days) pain 4.43 ± 2.82 7.35 ± 18.24 0.591 vomiting 4.00 ± 2.00 3.66 ± 3.69 0.329 fever 3.75 ± 2.06 9.84 ± 17.45 0.589 ileus 2.71 ± 1.60 2.74 ± 1.85 0.924 vital signs systolic bp (mmhg) 113.57 ± 21.63 109.76 ± 18.31 0.635 pulse rate (bpm) 111.57 ± 19.23 104.74 ± 17.30 0.342 investigations haemoglobin (g/dl) 11.38 ± 2.23 12.66 ± 3.17 0.403 tlc (/cu.mm) 9663.3 ± 3447.4 12408.4 ± 9243.02 0.727 platelet count (/cu.mm) 187.67 ± 56.89 1471.42 ± 9188.72 0.384 blood urea (mg/dl) 80.60 ± 64.35 59.33 ± 45.46 0.269 serum creatinine (mg/dl) 1.63 ± 1.82 1.29 ± 0.90 0.604 inr 1.21 ± 0.11 1.41 ± 0.55 0.492 serum albumin (g/dl) 3.00 ± 0.43 3.29 ± 0.84 0.334 delay in surgery yes 6 (5.7) 99 (94.3) 0.251 site of perforation gastric (type i) 1 (20.0) 4 (80.0) 0.045 gastric (type iii) 4 (5.9) 64 (94.1) duodenum* 1 (100.0) 0 (0.0) jejunum 1 (33.3) 2 (66.7) management operative 7 (4.7) 141 (95.3) 1.000 non-operative 0 (0.0) 18 (100.0) data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure; inr: international normalised ratio; tlc: total leucocyte count. *: duodenum, caecum, and ascending colon. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 8 table 2: association between different grades of clavien-dindo postoperative complications and preoperative variables parameters post-operative complications based on clavien-dindo grade p i (n =1) ii (n = 21) iiia (n=15) iiib (n=7) iva (n=23) ivb (n = 4) v (n = 15) age ( years) mean ± sd 42.00 ± 0 35.81 ± 10.97 39.93 ± 15.81 43.57 ± 14.66 44.04 ± 16.83 51.75 ± 11.00 50.07 ± 18.80 0.199 gender male 1 (1.4) 14 (20.3) 12 (17.4) 7 (10.1) 20 (29.0) 4 (5.8) 11 (15.9) 0.448 female 0 (0.0) 7 (41.2) 3 (17.6) 0 (0.0) 3 (17.6) 0 (0.0) 4 (23.5) co-morbidity addiction 1 (1.9) 14 (25.9) 8 (14.8) 2 (3.7) 15 (27.8) 2 (3.7) 12 (22.2) 0.307 symptom pain 1 (1.2) 21 (24.7) 15 (17.6) 6 (7.1) 23 (27.1) 4 (4.7) 15 (17.6) 1.000 vomiting 1 (2.6) 16 (42.1) 6 (15.8) 1 (2.6) 7 (18.4) 3 (7.9) 4 (10.5) 0.005 fever 1 (3.6) 6 (21.4) 8 (28.6) 3 (10.7) 4 (14.3) 1 (3.6) 5 (17.9) 0.177 ileus 1 (1.8) 11 (19.3) 8 (14.0) 5 (8.8) 18 (31.6) 3 (5.3) 11 (19.3) 0.422 duration of symptoms (days) pain 2.00 ± 0 3.38 ± 1.75 16.40 ± 37.16 3.83 ± 3.25 4.22 ± 2.68 4.50 ± 1.29 13.87 ± 30.92 0.054 vomiting 2.00 ± 0 2.69 ± 1.40 5.67 ± 3.50 1.00 ± 0 4.43 ± 3.87 4.33 ± 1.53 4.50 ± 3.79 0.186 fever 2.00 ± 0 7.33 ± 6.25 5.62 ± 4.96 4.00 ± 1.73 4.25 ± 3.86 6.00 ± 0 10.00 ± 9.90 0.950 ileus 2.00 ± 0 2.27 ± 1.42 4.50 ± 2.98 1.20 ± 0.45 3.28 ± 1.96 3.67 ± 2.08 2.36 ± 1.29 0.027 vital signs pulse rate (bpm) mean ± sd 128.0 ± 0 107.6± 19.12 106.00 ± 11.50 115.5 ± 25.7 106.3 ± 16.1 110.2 ± 16.8 112.07 ± 17.1 0.758 systolic bp (mmhg) mean ± sd 128.0 ±0 109.50 ± 16.4 114.20 ± 20.8 118.4 ± 11.7 114.78 ± 10.43 110.5 ± 30.44 100.5 ± 23.06 0.167 <100 0 (0.0) 5 (29.4) 2 (11.8) 0 (0.0) 1 (5.9) 2 (11.8) 7 (41.2) 0.013 ≥100 1 (1.5) 15 (22.1) 13 (19.1) 7 (10.3) 22 (32.4) 2 (2.9) 8 (11.8) diastolic bp (mmhg) mean ± sd 70.00 ± 0 75.95 ± 11.27 76.27 ± 23.89 78.43 ± 8.83 69.30 ± 9.45 70.00 ± 14.14 61.87 ± 13.45 0.051 investigations haemoglobin (g/dl) 12.64 ± 3.15 11.65 ± 2.76 11.55 ± 3.66 12.36 ± 3.17 12.95 ± 2.52 9.34 ± 2.83 0.059 tlc (/cu.mm) 12395.1±7774.4 18355.6±11001.3 8580.0±6869.9 10847.4±7975.3 7480.6±5304.0 13102.5±15258.4 0.089 platelet count (/cu.mm) 282.05 ± 155.89 263.85 ± 244.21 280.29 ± 232.78 231.32 ± 105.79 202.67 ± 160.75 5508.55 ± 17409.69 0.597 blood urea (mg/dl) 51.38 ± 27.00 61.41 ± 51.76 48.57 ± 20.75 80.47 ± 62.90 170.82 ± 97.71 76.00 ± 47.52 0.103 cr (mg/dl) mean ± sd 1.21 ± 0.65 1.10 ± 0.53 0.78 ± 0.29 1.54 ± 1.37 3.09 ± 1.39 1.66 ± 1.20 0.058 ≤2 mg/dl 0 (0.0) 16 (26.2) 14 (23.0) 7 (11.5) 15 (24.6) 1 (1.6) 8 (13.1) 0.043 >2 mg/dl 0 (0.0) 3 (20.0) 1 (6.7) 0 (0.0) 4 (26.7) 3 (20.0) 4 (26.7) inr mean ± sd 1.40 ± 0.35 1.38 ± 0.20 1.23 ± 0.09 1.55 ± 0.81 1.25 ± 0.22 1.80 ± 0.50 0.154 ≤1.5 0 (0.0) 10 (25.0) 10 (25.0) 5 (12.5) 11 (27.5) 2 (5.0) 2 (5.0) 0.017 >1.5 0 (0.0) 6 (28.6) 3 (14.3) 0 (0.0) 4 (19.0) 0 (0.0) 8 (38.1) serum albumin (g/dl) 3.38 ± 0.89 3.18 ± 0.73 2.61 ± 0.38 2.95 ± 0.83 3.10 ± 0.46 2.86 ± 0.84 0.081 imaging 0.761 delay in surgery 1 (1.8) 15 (27.3) 9 (16.4) 3 (5.5) 14 (25.5) 3 (5.5) 10 (18.2) 0.879 site of perforation 0.367 management operative 1 (1.2) 21 (25.6) 13 (15.9) 7 (8.5) 21 (25.6) 4 (4.9) 15 (18.3) 0.682 non-operative 0 (0.0) 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure; cr: creatinine; inr: international normalised ratio; tlc: total leucocyte count; bpm: beat per minute. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e86 table 3: association between need for icu admission and preoperative parameters parameters need for icu admission p yes (n = 32) no (n = 138) age ( years) mean ± sd 46.59 ± 17.33 41.62 ± 15.51 0.141 gender male 28 (20.0) 112 (80.0) female 4 (13.3) 26 (86.7) co-morbidity addiction 23 (20.4) 90 (79.6) 0.472 symptom pain 32 (18.9) 137 (81.1) 1.000 vomiting 12 (15.4) 66 (84.6) 0.275 fever 9 (20.5) 35 (79.5) 0.765 ileus 21 (21.0) 79 (79.0) 0.409 duration of symptoms (days) pain 9.81 ± 24.18 6.91 ± 17.08 0.575 vomiting 2.83 ± 1.40 3.70 ± 3.85 0.723 fever 5.00 ± 6.00 10.86 ± 19.03 0.317 ileus 2.67 ± 1.32 2.77 ± 2.00 0.693 pulse rate (bpm) mean ± sd 111.41 ± 15.69 102.87 ± 16.72 0.011 <100 6 (9.8) 55 (90.2) 0.020 ≥100 26 (24.5) 80 (75.5) systolic bp (mmhg) mean ± sd 105.09 ± 22.42 112.01 ± 16.00 0.029 <100 12 (42.9) 16 (57.1) <0.001 ≥100 20 (14.4) 119 (85.6) diastolic bp (mmhg) mean ± sd 64.53 ± 13.75 72.67 ± 12.23 0.001 laboratory haemoglobin (g/dl) 12.26 ± 2.96 12.69 ± 3.27 0.505 tlc (/cu.mm) 11794.44 ± 9330.32 12709.10 ± 9307.87 0.406 platelet count (/cu.mm) 2390.15 ± 11114.30 968.27 ± 8028.70 0.224 blood urea (mg/dl) 77.87 ± 61.75 54.17 ± 40.04 0.030 serum creatinine (mg/dl) mean ± sd 1.70 ± 1.19 1.18 ± 0.84 0.045 ≤2 20 (15.2) 112 (84.8) 0.032 >2 8 (36.4) 14 (63.6) inr mean ± sd 1.69 ± 0.75 1.30 ± 0.31 0.018 ≤1.5 10 (10.9) 82 (89.1) 0.017 >1.5 9 (31.0) 20 (69.0) serum albumin (g/dl) mean ± sd 2.94 ± 0.79 3.37 ± 0.84 0.016 <2.5 g/dl 7 (30.4) 16 (69.6) 0.149 ≥2.5 g/dl 20 (16.8) 99 (83.2) delay in surgery yes 18 (17.1) 87 (82.9) 0.572 hours 14.78 ± 12.12 12.67 ± 22.15 0.191 reason for the delay unavailability of ot slot 14 (14.7) 81 (85.3) unavailability of icu/ventilator 0 (0.0) 1 (100.0) delay in diagnosis 0 (0.0) 3 (100.0) initial resuscitation 3 (100.0) 0 (0.0) 0.016 left against medical advice 0 (0.0) 0 (0.0) non-operative management 1 (50.0) 1 (50.0) delay in ct scan 0 (0.0) 1 (100.0) impending perforation 0 (0.0) 1 (100.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 10 table 3: association between need for icu admission and preoperative parameters parameters need for icu admission p yes (n = 32) no (n = 138) management operative 29 (19.6) 119 (80.4) 0.531 non-operative 2 (11.1) 16 (88.9) data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure; inr: international normalised ratio; tlc: total leukocyte count; icu: intensive care unit; ct: computed tomography; ot: operation theatre; bpm: beat per minute. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e86 table 4: association between postoperative 30-day mortality and preoperative parameters parameters mortality p present (n = 23) absent (n=162) age ( years) mean ± sd 49.00 ± 18.51 41.70 ± 15.45 0.072 gender male 17 (11.4) 132 (88.6) 0.403 female 6 (16.7) 30 (83.3) co-morbidity addiction 14 (11.5) 108 (88.5) 0.583 symptom pain 23 (12.6) 160 (87.4) 1.000 vomiting 9 (10.2) 79 (89.8) 0.358 fever 7 (14.9) 40 (85.1) 0.577 ileus 15 (13.8) 94 (86.2) 0.555 duration of symptoms (days) pain 14.43 ± 29.99 6.21 ± 15.29 0.534 vomiting 3.44 ± 2.65 3.70 ± 3.75 0.657 fever 7.86 ± 8.88 9.57 ± 17.87 0.844 ileus 2.40 ± 1.12 2.79 ± 1.91 0.706 pulse rate (bpm) mean ± sd 112.43 ± 15.33 103.92 ± 17.42 0.020 <100 4 (6.2) 60 (93.8) 0.054 ≥100 19 (16.2) 98 (83.8) systolic bp (mmhg) mean ± sd 98.26 ± 22.49 111.60 ± 17.15 0.002 <100 12 (34.3) 23 (65.7) <0.001 ≥100 11 (7.5) 135 (92.5) diastolic bp (mmhg) mean ± sd 61.70 ± 12.04 72.08 ± 12.96 <0.001 laboratory data haemoglobin (g/dl) mean ± sd 10.17 ± 2.62 12.94 ± 3.09 <0.001 <8 g/dl 3 (33.3) 6 (66.7) 0.061 ≥8 g/dl 15 (9.6) 141 (90.4) tlc (/cu.mm) 14282.7± 14684.3 12135.6 ± 8356.3 0.648 platelet count (/cu.mm) 3464.1 ± 13610.6 1197.4 ± 8415.4 0.165 blood urea nitrogen (mg/dl) 91.61 ± 68.97 55.63 ± 40.37 0.012 serum creatinine (mg/dl) mean ± sd 1.78 ± 1.22 1.24 ± 0.87 0.063 ≤2 mg/dl 14 (10.1) 125 (89.9) 0.094 >2 mg/dl 6 (23.1) 20 (76.9) inr mean ± sd 1.91 ± 0.80 1.35 ± 0.47 0.002 ≤1.5 4 (4.2) 92 (95.8) <0.001 >1.5 10 (30.3) 23 (69.7) serum albumin (g/dl) 2.89 ± 0.77 3.34 ± 0.83 0.027 mean ± sd 0.089 <2.5 g/d l 6 (24.0) 19 (76.0) ≥2.5 g/dl 13 (10.2) 115 (89.8) reason for the delay unavailability of ot slot 9 (9.5) 86 (90.5) unavailability of icu/ventilator 0 (0.0) 12 (100.0) delay in diagnosis 1 (33.3) 2 (66.7) 0.008 initial resuscitation 3 (100.0) 0 (0.0) left against medical advice 0 (0.0) 2 (100.0) non-operative management 0 (0.0) 2 (100.0) delay in investigations (ct) 0 (0.0) 1 (100.0) impending perforation 0 (0.0) 1 (100.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rai et al. 12 table 4: association between postoperative 30-day mortality and preoperative parameters parameters mortality p present (n = 23) absent (n=162) management operative 20 (13.5) 128 (86.5) 1.000 non-operative 2 (11.1) 16 (88.9) data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure; inr: international normalised ratio; tlc: total leukocyte count; icu: intensive care unit; ct: computed tomography; ot: operation theatre; bpm: beat per minute. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 27 emergency (2015); 3 (1): 27-32 original research epidemiology of alcohol poisoning and its outcome in the north-west of iran hamid reza morteza bagi1, mohammad tagizadieh2, payman moharamzadeh1, mahboob pouraghaei1, aynaz kahvareh barhagi3, kavous shahsavari nia4* 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran. 2. department of pathalogy, tabriz branch, islamic azad university, tabriz, iran. 3. department of medicine, islamic azad university, tabriz branch faculty of medicine, tabriz, iran. 4. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. *corresponding author: kavous shahsavari nia; road traffic injury research center, tabriz university of medical sciences, sina hospital, azadi ave, tabriz, iran. tel/fax: +984115412101. email: kavous.shahsavari@yahoo.com received: august 2014; accepted: september 2014 abstract introduction: alcohol poisoning is one of the main preventable causes of death, disability, and injury in many societies. ethanol and methanol are the most prevalent kinds of alcohol used. there is no any exact reports of alcohol poisoning and its outcome in iranian society. therefore, the present study was assessed the status of alcohol poisoning and its outcome in referees to the emergency department. methods: this is a cross-sectional study, which was done from july 2013 to 2014 in sina trauma center, tabriz, iran. the studied population included all alcoholpoisoning cases referred to this center. demographic variables, clinical evaluation, laboratory tests, and patient's outcome were evaluated. to assess the relation between evaluated factors and outcome of alcohol poisoning. after univariate analysis, a multivariate logistic regression was applied to evaluate independent risk factors for death. p<0.05 was considered as a significant level. results: lastly, 81 patients with alcohol poisoning were entered to the study (91.4% male) with the mean age of 27.9±10.4 years. ten (12.3%) subjects were dialyzed and 34 (42%) cases hospitalized that 3 (3.7%) of them died. the multivariate logistic regression test displayed that plasma creatinine level (or=2.2 95%cl: 1.8-2.5; p=0.015) and need for dialysis (or=6.4; 95%cl: 5.3-7.5; p<0.001) were the only risk factors of death among these patients. conclusion: the findings of the present study revealed that total mortality rate of referees to the emergency with alcohol poisoning was 3.7% all of whom related to methanol poisoning. based on this result, the mortality rate of methanol poisoning was estimated 20%. need for dialysis and increasing the creatinine level were accounted as independent risk factors of death. key words: ethanol; methanol; alcohol drinking; alcoholism; poisoning; mortality cite this article as: morteza bagi hr, tagizadieh m, moharamzadeh p, pouraghaei p, kahvareh barhagi a, shahsavari nia k. epidemiology of alcohol poisoning and its outcome in the north-west of iran. emergency. 2015;3(1):27-32. introduction: lcohol poisoning is one of the main preventable causes of death, disability, and injury in many societies. alcohol consuming is together with adverse social consequences, which include liver cirrhosis, mental illness, several cancers, pancreatitis, and fetal damage in pregnant women. also, alcohol consumption has a close relationship with social events such as drunk driving accidents, invasive and anti-social behaviors, family disruption, and dropping the individuals' performance (1-3). the prevalence of heavy alcohol use (at least 60 gram in each consumption) is variable in the world and reported as 7.5% in the general population (2). although heavy drinking in iran has been seen in less than 1% of alcoholics, it should be taken to account that most of alcohol consumption cases and their related outcome have not been reported because of the presence of social stigmas (4). thus, it is probable that the alcohol use have a higher rate than this number. world health organization (who) has put effort to monitoring health status and providing technical assistance as well as cash and non-cash supports in its priorities to control health problems of alcohol abuse. one of the most important proceedings of who is encouraging to data gathering regards to gaps of statistics especially in developing countries. this organization has launched for technical helps to members with the aim of assessing, monitoring of health problems, as well as related process of alcohol consumption and its harm effects (5). ethanol and methanol are the most prevalent kinds of ala this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com morteza bagi et al 28 cohol used. ethanol consumption causes to sleep disorders, stomach diseases (gastric ulcer), esophagus and liver involvements, malnutrition, increasing the blood pressure and risk of heart and brain failures, myasthenia, auditory hallucinations, amnesia lasting, increasing the risk of head and neck cancer and gastrointestinal cancer (6, 7). methanol consumption addition to all of these outcomes can also lead to blindness and even coma and death. methanol is a toxic alcohol, which is used in many liquids such as antifreezes, solvents, glass cleaners, etc.; but the main source of its abuse is homemade alcohols. during the process of ethanol production some methanol is also produced which cannot be removed in these places (8). in iran because of religious issues and legal and social inhibitions, production and consumption of alcohol is illegal. this issue causes that most parts of alcohol abuse in iran arise from homemade alcohols which in turn increase the probability of alcohol poisoning (9). in addition, fear of legal consequences causes that these cases often refer to health care centers after a long time. this causes that treatment proceedings would not effective enough and subsequently lead to a high rate of mortality from alcohol poisoning. however, in many of centers, the privacy of patients is kept secret and alcohol poisoning is not reported. consequently, there is no any exact report of alcohol poisoning and its outcome in iranian society. therefore, the present study was assessed the status of alcohol poisoning and its outcome in referees to the emergency department. methods: study design and setting this is a cross-sectional study, which was done in oneyear period from july 2013 to 2014 in sina trauma center, tabriz, iran. the main goal of this study was evaluating the alcohol poisoning and its consequences in admitted patients to the emergency department. this study was confirmed by ethical committee of tabriz university of medical sciences. the subjects participated to the study as voluntary and consent forms were given from them. subject the studied population included all alcohol-poisoning cases referred to the health centers. exclusion criteria were dissatisfaction from participation to the study and disability of patients to answer the questions. the strategy of determining the sample size was based on the studies with aim of assessing the frequency of an event. for this purpose and according to the previous studies, the prevalence of mortality in alcohol poisoning cases was estimated 28% (10). thus with taking the type one error equal to 5% (α=0.05) and accuracy of 10% (d=0.1), the least numbers of needed sample for the project were 77 patients. finally, 88 patients were evaluated. variables data of the present study was collected and registered in the checklist by a trained physician. evaluated information included demographic variables (gender, age, occupation, location, and the way of referring), clinical evaluation, laboratory tests, and patient's outcome. the time interval from consumption to admission to the emergency, medical history, drug history, alcohol consumption history among family members, relatives and friends, intention of use (recreational, addiction, economic or social problems, curiosity), and clinical signs on arrival (drunkenness, lung problems, heart problems, loss of consciousness, blurred vision and blindness) were evaluated. in addition, laboratory assessment included hematologic and biochemical tests, arterial blood gases, and urine tests were recorded, too. in this part, white blood cell (wbc), hemoglobin concentration (hb), and hematocrit level (hct) were evaluated as hematologic assessment. the level of sodium (na), potassium (k), blood urea nitrogen (bun), creatinine (cr), and blood sugar (bs) were also considered as biochemical tests. furthermore, blood acidity (ph), bicarbonate (hco3), partial pressure of carbon dioxide (paco2), chloride level, base excess, and anion gap in arterial blood gases were evaluated. evaluated outcomes primary outcome in the present study included need for dialysis, while secondary outcome contained with death of the patient and the occurrence of persistent symptoms. statistical analysis data were analyzed using stata version 11.0. quantitative data were reported as mean and standard deviation, qualitative data as frequency and percentage. to assess the relation between evaluated factors and outcome of alcohol poisoning, mann-whitney test (to compare quantitative and ordinal data), chi-square test, and fisher's exact test (for qualitative data) were used. to evaluate independent risk factors, a multivariate logistic regression was formulated to identify independent risk factors. in all analysis p<0.05 was considered as a significant level. results: finally, 81 patients with alcohol poisoning were entered to the study (91.4% male). the mean age of subjects was 27.9±10.4 years (range: 15-66). forty-four (61.1%) patients were self-employed, 11 (15.2%) student, and 9 (12.5%) unemployed. most of subjects were single (64.1%). forty-three (68.2%) of cases had diploma and 10 (15.9%) were under diploma. only 1 (1.2%) patient lived in the village. forty-nine (62.8%) cases by their relatives and 23 (29.5%) by emergency medical system (ems) were referred to the health care center. the mean of time interval between consumption to admission to the emergency ward was 7.8±16.4 hours (range: 1-96). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 29 emergency (2015); 3 (1): 27-32 in assessing of the medical history, 2 (2.6%) patients suffered from mental illness and 2 (2.6%) ones had hypertension. also, 3 (4%) of them had a history of using psychiatric drugs and 2 (2.6%) cases had consumed cardiac drugs. the history of alcohol consumption in 63 (79.8%) patients was positive. additionally, 50 (60.5%) patients had smoking history. only 18 (22.5%) subjects had a history of using opium as orally or by smoking. history of alcohol consumption was reported in 1 (1.5%) case by father, 10 (12.4%) by brother, 2 (2.5%) by sister, 1 table 1: the relationship between demographic and clinical factors with alcohol-related death evaluated factors patient's status p* dead alive age (mean±sd) 6.7±24.3 10.5±28.0 gender male 2 (2.7) 72 (90.3) 0.12 female 1 (14.3) 6 (85.7) occupation self-employed 0 (0) 44 (100) 0.02 high school students 0 (0) 11 (100) undergraduate students 1 (33.3) 2 (66.7) employee 0 (0) 3 (100) unemployed 1 (11.1) 8 (88.9) prisoned 0 (0) 1 (100) the way of referring by self 0 (0) 3 (100) by relatives 1 (2.0) 48 (98.0) ambulance 2 (8.7) 21 (91.3) police 0 (0) 3 (100) medical history without history 3 (4.3) 67 (95.7) 0.99 mental illness 0 (0) 2 (100) hypotension 0 (0) 1 (100) hypertension 0 (0) 2 (100) migraine 0 (0) 1 (100) asthma 0 (0) 1 (100) history of drug usage without history 3 (4.3) 67 (95.7) 0.99 cardiac 0 (0) 2 (100) psychiatry 0 (0) 3 (100) asthma 0 (0) 1 (100) smoking 1 (2) 49 (98) 0.99 drinking 2 (3.2) 61 (96.8) 0.5 opium use 0 (0) 18 (100) 0.42 symptoms drunkenness 0 (0) 26 (100) 0.55 lung problems 1 (33.3) 2 (66.7) 0.1 heart problems 0 (0.0) 0 (0.0) ----- loss of consciousness 2 (6.2) 30 (93.8) 0.56 blurred vision 1 (3.4) 28 (96.6) 0.99 blindness 0 (0.0) 0 (0.0) ----- nausea and vomiting 2 (5.6) 33 (94.4) 0.58 cause of use recreational 2 (4.2) 46 (95.8) 0.99 addiction 1 (7.7) 12 (92.1) 0.4 economic problems 0 (0) 2 (100) 0.99 social problems 0 (0) 8 (100) 0.99 curiosity 0 (0) 1 (100) 0.42* *based on fisher's test; sd: standard deviation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com morteza bagi et al 30 (1.25%) by spouse, and 47 (58%) by friends. the reason of alcohol consumption in 48 (59.3%) subjects was recreational, 13 (16%) addiction, 8 (10%) social problems, and 2 (2.5%) economic problems. nausea and vomiting were the most prevalent signs (44.4%). moreover, drunkenness in 26 (32.5%), loss of consciousness in 32 (39.5%), blurred vision in 29 (35.8%), and lung problems in 3 (3.7%) patients were observed (table 2). finally, 10 (12.3%) subjects were dialyzed. of 81 patients 34 (42%) cases were hospitalized that 3 (3.7%) of them died. the mean of patients' hospitalization was 1.4±2.7 days (range: 1-14). three (3.7%) patients also had complication, one case had wernicke-korsakoff syndrome and metabolic encephalopathy, one blurred vision, and one optic neuropathy. the relation between mortality and studied factors the mean age of died patients was 24.3±6.7 years which had no significant difference with living ones (28±10.5 years) (p=0.69). in addition no significant relation was seen between gender (p=0.12), level of education (p=0.32), occupation (p=0.1), and the type of referring (p=0.4) with patients' death. medical history (p=0.99), drug history (p=0.99), alcohol consumption history (p=0.5), time interval from consumption to admission (p=0.99), smoking (p=0.99), opium consumption (p=0.42) and its intention did not relate to patients' death, too. it is worth noting that none of symptoms had significant relationship with mortality of patients (table 1). while, need for dialysis had a significant relation with mortality (p<0.001). plasma sodium level (p=0.2), bun (p=0.29), wbc (p=0.37), hb (p=0.25), blood ph (p=0.12), bicarbonate (p=0.38), paco2 (p=0.7), chloride (p=0.9), base excess (p=0.11), and anion gap (p=0.64) had no relation with death. on the other hand, increasing the potassium level (p=0.04), creatinine (p=0.006), bs (p=0.04), dialysis (p<0.001), and hct (p=0.04) showed a significant relation with patients' mortality (table2). the multivariate logistic regression displayed that plasma creatinine level (or=2.2 95%cl: 1.8-2.5; p=0.015) and need for dialysis (or=6.4; 95%cl: 5.3-7.5; p<0.001) were the only risk factors of death among these patients (table 3). discussion the findings of this study showed that the mortality rate of alcohol poisoning in the studied population was 3.7% of whom 12.3% needed to have dialysis. in addition, 3 (3.7%) patients had neurologic complications. increasing the plasma creatinine level and need for dialysis were estimated as the only risk factors of alcohol poisoning related death. mortality of alcohol poisoning has shown different rate among various studies which arises from differences in geographical regions, race, pattern of alcohol drinking, and type of alcohol. for example, who report in 2014 showed that globally in population over 15 years old, each person consumes in average about 6.2 liters alcohol annually. the prevalence of heavy drinking is high in russia while in scandinavian countries the least drinking has been seen. this reports has shown that alcohol drinking is cause of deaths in 5% of cancers, 5.8% of cardiovascular and diabetes diseases, 23.6% of table 2: the relation between hematologic and biochemical finding with alcohol-related death factor* patient's status p** alive dead sodium (meq/l) 140.3 (9.7) 136.3 (5.7) 0.2 potassium (meq/l) 4.0 (0.6) 4.6 (0.4) 0.04 blood urea nitrogen (mg/dl) 29.2 (11.5) 51.3 (38.2) 0.3 creatinine (mg/dl) 1.0 (0.9) 3.8 (3.6) 0.006 blood sugar (mg/dl) 127.1 (61.3) 275 (206.4) 0.04 white blood cell (n/m3) 10001 (3802.7) 13750 (6717.5) 0.37 hemoglobin (g/dl) 14.9 (4.5) 16.2 (2.4) 0.25 hematocrit (%) 42.8 (6.6) 49.2 (3.2) 0.04 ph 7.28(0.2) 7.18 (0.12) 0.12 bicarbonate (meq/l) 21.1 (7.0) 16.6 (8.9) 0.37 paco2 (mm hg) 40.5 (10.6) 41.8 (16.2) 0.7 chloride (meq/l) 105.0 (8.3) 104.9 (5.1) 0.9 base excess -1.5 (6.7) -10.1 (10.0) 0.11 anion gap (meq/l) 18.3 (13.3) 19.5 (16.1) 0.64 *data was reported as mean (standard deviation); **all p were based on mann-whitney test table 3: the independent risk factors of alcohol-related death factors odds ratio 95% confidence interval p increasing the creatinine level 0.015 1.8-2.5 2.2 need for dialysis <0.001 5.3-7.5 6.4 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 31 emergency (2015); 3 (1): 27-32 gastrointestinal disease, and 35.2% of accidents (15.2% unintentional and 20% intentional events). totally, 5.9% of deaths are related to alcohol abuse (4). moghaddam and pajoumand stated that mortality rate of methanol poisoning was 48%; among survived persons 3 (23%) of them became blind and the rest discharged with full recovery. this study showed a significant relation between serum ph level and interval time between intake of methanol and admission with patients' death (11). the mortality rate in shadnia et al. was reported 30% (10). sanaee et al. declared 28% mortality in methanol poisoning, while kute and colleagues showed 3.3% (12, 13). additionally, in ghannoum et al. study mortality of methanol and ethylene glycol were reported 2.9% and 2.4%, respectively (14). as can be seen, there are many differences among various studies. in the present study, mortality rate was estimated 3.7%. when patients with anion gap above 10 meq per liter, osmolal gap above 11 meq per liter, and metabolic acidosis (three signs of methanol poisoning) were separated from others, it was determined that 15 patients were suspicious for methanol poisoning. three died patients were in this group, too. based on above findings, mortality rate of methanol poisoning was 20%, near to the results of other studies. moreover, the findings of the present project showed that increasing the plasma creatinine level and need to have dialysis are the only risk factors of alcohol-related death. whereas shadnia et al. stated that coma, blood levels of methanol, paco2, and bs are risk factors of death in these patients; in their research no relation was found between ph, bicarbonate, and time duration from poisoning to beginning the dialysis and death (10). sanaee et al. showed that the only independent predictive factor of methanol-related death is hyperglycemia (12). but, study of kute and colleagues presented that metabolic acidosis, need to use ventilator, and coma or seizure on admission are factors associated with mortality of methanol poisoning (13). as can be seen, there is a notable difference among studies in risk factors of death for alcohol poisoning cases. for instance, in some researches ph level was accounted, in others coma, etc. therefore, presenting a total conclusion has not yet been possible in this area. it is suggested that in future studies evaluation of risk factors related to alcohol poisoning to be performed by using an acceptable volume sample with assessing all the possible effective factors. several strategies have been presented for controlling adverse effects of alcohol consumption. however, they should totally be performed to reduce the harmful effects of alcohol consumption and its related problems for both the person and society. these policies can be designed in the national, regional, and universal levels (15). these strategies can be involved in different aspects of production, sales, and management of consumers, which concluded accessibility to alcohol, the way of its selling, its price, drunk driving, preventive interventions, and therapy in the health care system. for this purpose, government pressures can be used as an efficient tool (16); say, iran has executed strict laws regarding production as well as buy and sale of alcohol to prevent alcohol consumption. however, the present evidences revealed that these policies do not have appropriate preventive role. indeed, for decreasing the destructive effects of alcohol consumption, governments should be aware from economic and social effects. health system also has a critical role in confronting with problems related to alcohol by extending and providing health services for preventive goals. for instance, screening and brief intervention with referral to treatment could be representative the cost-effectiveness and usefulness of proceedings (17). to this end, the first step is increasing the capacity of health system and social welfare to present preventive, therapeutic, and care services regarding alcohol consumption (18, 19). increasing the capacity includes alcohol cessation, creating a committee in the health ministry to control the alcohol abuse and holding training classes, improving the knowledge and attitude of the society to prevent alcohol consumption especially homemade products, and informing people from risks of alcohol abuse specifically methanol. this is a crosssectional study performed by questioning from patients or their relatives about patients' history. however, because of two reasons the bias cannot be ignored; first cause is arisen from observational studies that recall bias cannot be completely removed, and another one origins from social stigma against alcohol consuming in iranian society. based on these statements, the information about the history of alcohol consumption and other substance abuse with their cause of using may be not accurate enough. on the other hand, lacking of laboratory equipment to measure the blood methanol level caused that methanol poisoning could not exactly separated from ethanol poisoning. conclusion: the findings of the present study revealed that total mortality rate of referees to the emergency with alcohol poisoning was 3.7% all of whom related to methanol poisoning. based on this result, the mortality rate of methanol poisoning was estimated 20%. in addition, 12.3% of patients needed to have dialysis and 42% were hospitalized. it is worth noting that 3.7% of cases had neurologic complications. need for dialysis and increasing the creatinine level were accounted as independent risk factors of death. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of sina hospital of tabriz, iran. conflict of interest: none this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com morteza bagi et al 32 funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. babor t. alcohol: no ordinary commodity: research and public policy: oxford university press; 2010. p. 12-7. 2. organization wh. global status report on alcohol and health2014: world health organization; 2014. p. 1-72. 3. coutelle c, ward p, fleury b, et al. laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione s-transferase m1 polymorphisms. hum genet. 1997;99(3):319-25. 4. poznyak v, fleischmann a, rekve d, rylett m, rehm j, gmel g. the world health organization’s global monitoring system on alcohol and health. alcohol res. 2014;35(2):244-9. 5. world health organization. alcohol epidemiology, monitoring, and information system. genova: 2014. 6. dennis lk, hayes rb. alcohol and prostate cancer. epidemiol rev. 2013;23(1):110-4. 7. bagnardi v, rota m, botteri e, et al. light alcohol drinking and cancer: a meta-analysis. ann oncol. 2013;24(2):301-8. 8. tramacere i, negri e, pelucchi c, et al. a meta-analysis on alcohol drinking and gastric cancer risk. ann oncol. 2011;23(1):28-36. 9. mostafazadeh b, eghbali h. an epidemiologic study on methyl alcohol poisoning in tehran, iran. asia pac j med toxicol. 2014;3(1):8-12. 10. shadnia s, rahimi m, soltaninejad k, nilli a. role of clinical and paraclinical manifestations of methanol poisoning in outcome prediction. j resmed sci. 2013;18(10):865-9. [persian]. 11. moghaddam sab, pajoumand a. prognostic factors including clinical manifestation and paraclinic finding in sever methanol toxicity. life sci j. 2014;11(2s):11-4. 12. sanaei-zadeh h, esfeh sk, zamani n, jamshidi f, shadnia s. hyperglycemia is a strong prognostic factor of lethality in methanol poisoning. j med toxicol. 2011;7(3):189-94. 13. kute v, godara s, shah p, et al. hemodialysis for methyl alcohol poisoning: a single-center experience. saudi j kidney dis transpl. 2012;23(1):37-42. 14. ghannoum m, hoffman rs, mowry jb, lavergne v. trends in toxic alcohol exposures in the united states from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments. semin dial. 2014;27(4):395-401. 15. ringwalt cl, paschall mj, gitelman am. alcohol prevention strategies on college campuses and student alcohol abuse and related problems. j drug educ. 2011;41(1):99-118. 16. paltzer j, black p, moberg dp. evaluating community readiness to implement environmental and policy-based alcohol abuse prevention strategies in wisconsin. j alcohol drug educ. 2013;57(3):27-32. 17. puskar k, gotham hj, terhorst l, et al. effects of screening, brief intervention, and referral to treatment (sbirt) education and training on nursing students’ attitudes toward working with patients who use alcohol and drugs. subst abus. 2013;34(2):122-8. 18. connor j. healthy alcohol policy as an injury prevention strategy. inj prev. 2012;18(suppl 1):a14. 19. chinman m, burkhart q, ebener p, et al. the premises is the premise: understanding off-and on-premises alcohol sales outlets to improve environmental alcohol prevention strategies. prev sci. 2011;12(2):181-91. archives of academic emergency medicine. 2022; 10(1): e87 br i e f re p o rt aromatherapy with isopropyl alcohol versus intravenous ondansetron in management of mild brain trauma nausea and vomiting; a randomized clinical trial behrang rezvani kakhki1∗, tahereh ghasemi1, elnaz vafadar moradi1, zahra abbasi shaye2, seyed mohammad mousavi1 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. clinical research development center, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: august 2022; accepted: september 2022; published online: 31 october 2022 abstract: introduction: nausea and vomiting are common complaints among patients who refer to the emergency department with head trauma. this study aimed to compare the effect of aromatherapy with isopropyl alcohol versus intravenous ondansetron in management of mild head trauma nausea and vomiting. methods: this randomized clinical trial was conducted on patients with isolated mild head trauma complaining of nausea and vomiting who were referred to emergency department during a 6-month period. patients were randomly divided into control (iv ondansetron + aromatherapy with saline) and intervention (iv saline + aromatherapy with isopropyl alcohol) groups. the frequency of vomiting and the severity of nausea (from 0 to 100 with the verbal scaling) were written before, and 10 and 30 minutes after intervention and compared between groups. results: a total of 210 patients (105 patients in each group) with a median age of 38 years were included in the study, 112 (54.3%) of which were male. ten minutes after aromatherapy, no significant difference was observed in nausea and vomiting between the two groups (p >0.05). nausea score after 30 minutes (p = 0.015) was significantly lower in the intervention group compared to the control group, but vomiting after 30 minutes (p <0.001) was higher in the intervention group. conclusion: aromatherapy using isopropyl alcohol significantly reduced nausea of patients with mild isolate head trauma after 30 minutes. regarding vomiting, no favorable result was observed in this study. however, the frequency of vomiting was reduced in both control and intervention groups. keywords: aromatherapy; odorants; head injuries, closed; brain injuries, traumatic; 2-propanol cite this article as: rezvani kakhki b, ghasemi t, vafadar moradi e, abbasi shaye z, mousavi sm. aromatherapy with isopropyl alcohol versus intravenous ondansetron in management of mild brain trauma nausea and vomiting; a randomized clinical trial. arch acad emerg med. 2022; 10(1): e87. https://doi.org/10.22037/aaem.v10i1.1792. 1. introduction one of the main causes of mortality and disability in persons between the ages of 1 and 45 is a traumatic brain injury (tbi). the most frequent triggers of tbi are trauma, falls, car accidents, and sports-related injuries (1, 2). driving accidents are the most significant and frequent cause of head injuries in iran and asia (3, 4). since the number of patients with head trauma complaints in the emergency room is high and nausea and vomiting are common complaints among these pa∗corresponding author: behrang rezvani kakhki; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. e-mail: rezvanikb@mums.ac.ir, tel: +989153114371, orcid: https://orcid.org/0000-0003-3715-6618. tients (5), finding a safe, fast and effective treatment solution in the emergency room is needed and many medications are presented in literature for nausea control, while evidence on post-head trauma nausea is less available (6-9). aromatherapy is a safe, low-cost, and non-invasive solution, which can complement existing therapeutic strategies. aromatherapy aims to use scents and aromatic oils by inhalation or even with massage and sometimes orally to eliminate various unpleasant conditions such as nausea, vomiting, pain, stress, mental restlessness, insomnia, and reaching the desired state (10). numerous tests have shown that isopropyl alcohol is effective in treating nausea and vomiting after surgery (10). several animal models have shown the safety of isopropyl alcohol (11, 12). human studies have not been conducted after inhalation of isopropyl alcohol (10). in a meta-analysis conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rezvani kakhki et al. 2 ducted by gong et al. with the aim of evaluating the effect of aromatherapy on anxiety in patients, the results showed that aromatherapy with different essential oils can significantly reduce anxiety regardless of the cause of anxiety. however, the proper dosage of essential oils needs more research (13). since anti-nausea injection treatments have their own concerns, such as lack or absence of drugs, and drug allergies, finding another solution to get rid of these symptoms is useful. in addition, with aromatherapy, the patient can control the symptoms of nausea and vomiting by him/herself, and there is no need for a nurse to be constantly present at the patient’s bedside in the emergency room. aromatherapy has been used to control nausea and vomiting for various reasons (14) but no article has been published about the control of nausea and vomiting caused by mild head trauma by aromatherapy, yet. this study aimed to compare the effect of aromatherapy with isopropyl alcohol versus intravenous ondansetron in management of nausea and vomiting following mild isolated head trauma. 2. methods 2.1. study design and setting the present study is a randomized, single-blind clinical trial that was conducted on patients with nausea and vomiting following isolated mild head trauma, who were referred to the emergency department of shahid hashminejad hospital, mashhad, iran, during a 6-month period from december 2019 to june 2020. before entering the patients in this study, the research process was explained and informed consent was obtained from them. in all stages of the study, the researchers adhered to the ethical principles of helsinki declaration and the confidentiality of patient information. all the costs of this project were covered by the researchers and no additional costs were incurred by the patients. this study was approved by the ethics committee of mashhad university of medical sciences under the ethical code "ir.mums.medical.rec.1398.840" and registered in the clinical trial center of iran with the code "irct20161226031577n3" 2.2. participants patients referring to the emergency room due to isolated head trauma who were complaining from nausea (with severity level 1) and/or vomiting were selected for inclusion. isolated head trauma could be due to reasons such as an accident where only the patient suffered head trauma, accidents at work, or head trauma with a hard object. patient non-cooperation; glasgow coma scale (gcs) <13; the presence of neurological defects; patient dissatisfaction; age below 14 years; the presence of olfactory defects before the trauma; prescribing medicine to the patient that causes nausea or vomiting (such as prescribing narcotics for the patient’s headache); the period of reduced level of consciousness less than 30 minutes; any forgetfulness of events before or after the accident (less than 24 hours after the accident); any change in the mental state at the scene of the accident (feeling lost, lack of awareness of time or place or person, confusion); were among the exclusion criteria. in addition, all subjects with missing data were excluded from the study and sampling was continued until reaching the required sample size. 2.3. intervention patients were divided into two groups, a and b, based on the table of random numbers. in group a (control), ondansetron was given intravenously and saline as aromatherapy, and in group b (intervention) saline was administered intravenously and isopropyl alcohol was applied for aromatherapy with 3 cc sprinkled on a gauze pad, which the patient used to inhale. 2.4. data gathering all demographic variables of the patient, vital signs of the patient at the time of visit, and the initial outcome after receiving ondansetron or isopropyl alcohol were recorded in a checklist. first, the frequency of vomiting and the severity of nausea was scored from 0 to 100 using verbal scaling criteria, and then the presence of vomiting and the degree of nausea were evaluated and scored from 0 to 100 using verbal scaling criteria on 2 other occasions, 10 and 30 minutes later. the difference in the score given by the patient showed the response to the treatment. the checklist included items such as age and gender of the patients, their medication history, the patient’s vital signs on arrival (o2 saturation (sat) and pulse rate (pr) measured by fingertip pulse oximeter, contec company, china; respiratory rate per minute; and blood pressure measured by omron blood pressure monitor, made in japan), the feeling of nausea before intervention based on verbal scaling (from zero to 100, zero showing no feeling of nausea and 100 indicating the worst nausea that the person can imagine), and the presence or absence of vomiting before intervention. vital signs and nausea were measured before and 10 minutes after intervention; presence or absence of nausea and vomiting were asked at 10 and 30 minutes after intervention. no further follow-ups were conducted after 30 minutes from intervention. 2.5. statistical analysis based on april et al.’s study (15) that reported mean nausea score of 16±19 in the aromatherapy group and 29±25 in the ondansetron group after intervention based on visual analogue scale (vas), and considering alpha 0.05 and power of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e87 table 1: baseline characteristics of studied participants at the time of admission to emergency department variable total intervention control p age (year) median (q1-q3) 38 (25.75-53.25) 35 (25-50) 41 (27-56) 0.122 gender male 112 (53.3) 55 (52.4) 57 (54.3) 0.782 female 98 (46.7) 50 (47.6) 48 (45.7) vital sign pulse rate (/min) 70 (64-84) 67 (61.78) 75 (64-86) 0.026 respiratory rate (/min) 20 (18-24) 22 (18-24) 20 (16-23) 0.003 oxygen saturation (%) 98 (97-100) 98 (97-100) 98 (97-99) 0.756 sbp (mmhg) 130 (110-140) 130 (110-145) 130 (112-140) 0.312 nausea score median (q1-q3) 40 (30-60) 50 (30-60) 40 (30-70) 0.916 vomiting yes 86 (40.95) 50 (47.6) 36 (34.3) 0.049 no 124 (59.05) 55 (52.4) 69 (65.7) data are presented as median (interquartile range; iqr) or frequency (%). sbp: systolic blood pressure. table 2: comparison of patients’ studied outcomes between the two groups 10 and 30 minutes after the intervention outcomes intervention control p value vomiting 10 min yes 45 (42.9) 32 (30.5) 0.63 no 60 (57.1) 73 (69.5) vomiting 30 min yes 40 (38.1) 6 (5.7) 0.001 no 65 (61.9) 99 (94.3) nausea score 10 min median (iqr) 40 (20-60) 30 (0-70) 0.95 nausea score 30 min median (iqr) 10 (0-30) 20 (0-65) 0.015 data are presented as median (inter quartile range; iqr) or frequency (%). min: minutes. 80% in the formula for estimating the mean in two independent communities, the required sample size was estimated to be 96 people in each group and considering 10% attrition, 105 people were included in each group (figure 1). after collecting the data, they were entered into spss version 22 software and described using appropriate tables, graphs, and indices, and then the chi-square or fisher test was used to compare qualitative variables in the two groups, if necessary. mann-whitney test was used to compare quantitative variables (according to variable distribution). the significance level in all tests was considered less than 0.05. 3. results 3.1. baseline characteristics of studied cases in total, 210 patients were included in the study, 112 (54.3%) were male and the rest were female with a mean age of 38 (iqr=27.5) years. baseline characteristics of all the study samples are provided in table 1. the vomiting rate had a lower incidence among the controls than among intervention group (p = 0.049). respiratory rate was lower in controls than in intervention group (p = 0.003) and the pulse rate was higher in the control group (p = 0.026). 3.2. comparing the studied outcomes nausea after 30 minutes (p = 0.015) in the intervention group was significantly less than = the control group. but vomiting after 30 minutes in the intervention group was more than the control group (p < 0.001). while 10 minutes after intervention, no significant differences were observed in case of vomiting rate or nausea score (p > 0.05). 32.38% (95% ci: 22.09 42.68) of patients experienced vomiting after 30 minutes under aromatherapy that they would not have under ondansetron. based on the number needed to harm (nnh), for every 3.1 (95% ci: 2.3, 4.5) patients treated with aromatherapy, 1 vomiting after 30 minutes will occur beyond those that would have happened under ondansetron. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rezvani kakhki et al. 4 figure 1: the study flowchart. 4. discussion the present study was conducted in order to investigate the effect of aromatherapy using isopropyl alcohol in comparison with intravenous ondansetron in controlling nausea and vomiting caused by mild head trauma in patients who referred to the emergency room with isolated head trauma. the results of our study showed that the rate of nausea of the patients, which was similar between the two groups at the beginning of the study, was significantly lower in the intervention group than in the control group after 30 minutes, and the aromatherapy performed in this group using isopropyl alcohol had significantly reduced nausea. of course, this reduction of nausea in the intervention group was not observed after 10 minutes, and probably more than 10 minutes was necessary for isopropyl alcohol inhalation to show its effect. regarding vomiting, as mentioned, the amount of vomiting at the beginning of the study and before aromatherapy or ondansetron administration was higher in the intervention group than in the control group. after 30 minutes of the study, this difference still existed between the two groups. however, the vomiting of the patients was reduced in both the intervention group and the control group; but in the control group, this decrease in the incidence of vomiting was more obvious (from 34% to 5.7%). apparently, in this study, isopropyl alcohol was not as effective as ondansetron in reducing vomiting. since we did not have a third group (a group without medication) in this study, it is not possible to comment on whether the use of isopropyl alcohol has an effect on reducing vomiting or not. there are similar studies that have shown that isopropyl alcohol has been effective in reducing vomiting, which will be discussed below. inhalation aromatherapy’s effect has been investigated for nausea control in different settings, ncluding the stem cell transplantation (15), stroke (16), and coronary bypass (17); this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e87 but most shreds of evidence are based on the trials of postoperative assessments (10). the literature review did not reveal any study with similar aromatherapy treatment for traumatic brain injury patients. in the case of traumatic brain injury, evidence was limited to some experimental animal models (18). on the other hand, clinical studies on aromatherapy in the emergency room have not separated different causes of nausea. isopropyl alcohol has been evaluated as the aromatherapy agent in some studies. in another study conducted in 2018 by lindblad et al. (19) in canada, the authors examined 122 adult patients presenting to the emergency department who complained of mild to moderate nausea and vomiting. in most patients, nausea and vomiting were caused by gastroenteritis. the results obtained from this study showed that on a scale of 1 to 100, the rate of nausea after 30 minutes from the start of treatment was 20 in the group of patients who inhaled isopropyl alcohol and 44 in the group of ondansetron patients. however, there was no significant difference between the two groups in the amount of vomiting and the length of hospital stay among the patients. no harmful side effects were observed in any of the groups. the results obtained in this study regarding the nausea of patients were similar to our study and showed the significant effect of isopropyl alcohol in reducing nausea of patients referred to the emergency room. of course, it is possible that the small sample size in lindblad et al.’s study has reduced the accuracy of their results. a clinical trial conducted by candemir et al. (20) showed fascinating results, the average score of nausea and vomiting in the intervention group after 2 minutes was significantly lower than the control group. also, the amount of nausea of the patients in the intervention group was reduced in each of the measured times compared to the previous time. in general, the results obtained from this study were similar to our study and indicate the significant effect of isopropyl alcohol in reducing nausea among emergency patients. however, the difference between the two studies is that in our study, more time was needed for the anti-nausea effects of isopropyl alcohol to develop. the reason for the difference in the results of the two studies may be related to the difference in the patients included in the study, because in candemir’s study, all patients referring to the emergency room with complaints of nausea and vomiting were included in the study, but in our study, only patients with head trauma were included in the study and the trauma patients included in our study may have delayed the use of gauzes impregnated with isopropyl alcohol to deal with the trauma situation by a few minutes, and this issue has led to the delayed appearance of nausea reduction results. in another study conducted in 2018 by april et al. in the united states, the authors divided 122 patients who referred to the emergency room with complaints of nausea and vomiting into three groups, which included oral ondansetron and inhaled isopropyl alcohol, oral placebo and inhaled isopropyl alcohol, and oral ondansetron and inhaled placebo. the obtained results showed that the average reduction of nausea after 30 minutes in patients of three groups (on a 100-point scale) was 30, 32 and 9 units, respectively. also, in the mentioned groups, 27.5%, 25% and 45% of patients needed to receive additional medicine to reduce nausea. in april et al. study, as in our study, the positive effect of using isopropyl alcohol to reduce nausea in emergency patients has been reported. however, this study did not measure the vomiting rate of the patients. also, in this study, similar to our study, the nausea of the patients decreased after 30 minutes. our study had a larger sample size than this study (21). in a 2016 study in the united states, beadle et al. (22) investigated the effects of inhaled isopropyl alcohol on nausea and vomiting in emergency room patients. in this study, isopropyl alcohol was used as a placebo in one group of patients, and normal saline was used as a placebo in another group, and their nausea was checked after 10 minutes. 80 patients were included in the final analysis of the study. median nausea among the patients of the isopropyl alcohol group was lower than that of the patients in the placebo group. also, intervention group patients reported more satisfaction. in general, the results of this study were consistent with our study and showed the positive effect of isopropyl alcohol in reducing nausea in patients. also, considering that in this study, unlike our study, ondansetron was not prescribed for any of the two groups, we can be sure that the effects of reducing nausea observed in the intervention group were due to the inhalation of isopropyl alcohol. 5. limitation this study faced some limitations. first of all, there is a need for a placebo aromatherapy like a device with no essential oils and no effect on humidity for a double blinded method of rct. second, this was a single center study the results of which should be generalized to clinic after further larger studies with feasibility studies on implanting aromatherapy devices in emergency department. third, this study’s sample size was powered for nausea and vomiting that might have affected the results of vital signs assessment. also, we only followed patients for 30 minutes, which does not seem sufficient. 6. conclusion aromatherapy using isopropyl alcohol significantly reduced nausea of patients with mild isolate head trauma after 30 minutes. regarding vomiting, no favorable result was observed in this study. however, the frequency of vomiting was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rezvani kakhki et al. 6 reduced in both control and intervention groups. 7. declarations 7.1. acknowledgments none. 7.2. authors’ contributions mohd idzwan and tan maw pin designed the protocol on methodology, ethical approval, writing, review and editing the manuscript. mohd idzwan also supervised the completion of the manuscript. nor hadila was involved in research literature review, gaining ethical approval, sample collection, data analysis, writing and editing the manuscript. all authors reviewed and edited the manuscript and approved the final version of the manuscript. 7.3. authors’ contribution brk has designed the study. brk, tg, and evm planned the study protocols, samplings, and the interventions. zas and smm collected the data. brk and tg analyzed data. brk, evm, zas, and smm provided the drafts of manuscript. all authors have contributed to revisions and have confirmed final version. 7.4. conflict of interest none declared. 7.5. sources of funding this work is funded by mashhad university of medical sciences under the code ir.mums.medical.rec.1398.840; however, the funder has not interfered in any stage of this project. references 1. werner c, engelhard k. pathophysiology of traumatic brain injury. brit j of anest, 2007;99(1):4-9. doi: 10.1093/bja/aem131. 2. tsang kk, whitfield pc. traumatic brain injury: review of current management strategies. brit j of oral and maxillofacl surg. 2012 jun 1;50(4):298-308. 3. khan m, yaqoob u, hassan z, uddin mm. emergency department referral profile of traumatic brain injury records at a tertiary care hospital of pakistan. updat in emerg med, 2021, 1(1), 21–27. retrieved from http://uiemjournal.com/index.php/main/article/view/5. 4. aghakhani k, eslami sh, khara a, bijandi m. epidemiologic study of fall-related head injury in iran and its comparison with other countries. teh uni med j tums pub. 2018 oct 10;76(7):437-45. http://tumj.tums.ac.ir/article1-9108-en.html. 5. sturm jj, simon hk, khan ns, hirsh da. the use of 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aug 18;6(1):1-2. doi: 10.1038/srep31866. 19. lindblad aj, ting r, harris k. inhaled isopropyl alcohol for nausea and vomiting in the emergency department. can fam physician. 2018;64(8):580. retrieved from https://www.ncbi.nlm.nih.gov/ pubmed/30108075. 20. candemir h, akoglu h, sanri e, onur o, denizbasi a. isopropyl alcohol nasal inhalation for nausea in the triage of an adult emergency department. amerc j of emerg med. 2021;41:9-13. doi: 10.1016/j.ajem.2020.12.052. 21. april md, oliver jj, davis wt, ong d, simon em, ng pc, hunter cj. aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: a randomized controlled trial. ann emerg med. 2018 aug 1;72(2):184-93. doi: 10.1016/j.annemergmed.2018.01.016. epub 2018 feb 17. 22. beadle kl, helbling ar, love sl, april md, hunter cj. isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial. ann emerg med. 2016;68(1):1-9.e1. doi: 10.1016/j.annemergmed.2015.09.031. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 116 emergency (2016); 4 (3): 116-126 review article application of ultrasonography and radiography in detection of hemothorax; a systematic review and meta-analysis vafa rahimi-movaghar1, mahmoud yousefifard2, parisa ghelichkhani3, masoud baikpour4, abbas tafakhori5,6, hadi asady7, gholamreza faridaalaee8, mostafa hosseini9*, saeed safari10 1. sina trauma and surgery research center, tehran university medical sciences, tehran, iran. 2. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. 3. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 5. department of neurology, school of medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 6. iranian center of neurological research, tehran university of medical sciences, tehran, iran. 7. department of occupational health engineering, faculty of public health, tehran university of medical sciences, tehran, iran. 8. department of emergency medicine, maragheh university of medical sciences, maragheh, iran. 9. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 10. department of emergency medicine, shohedaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127. received: june 2015; accepted: august 2015 abstract introduction: hemothorax is one of the most prevalent injuries caused by thoracic traumas. early detection and treatment of this injury is of utmost importance in prognosis of the patient, but there are still controversial debates on the diagnostic value of imaging techniques in detection of hemothorax. therefore, the present study aimed to evaluate the diagnostic value of chest ultrasonography and radiography in detection of hemothorax through a systematic review and meta-analysis. methods: two independent reviewers performed an extended systematic search in databases of medline, embase, isi web of knowledge, scopus, cochrane library, and proquest. data were extract and quality of the relevant studies were assessed. the number of true positive, false positive, true negative and false negative cases were extracted and screening performance characteristics of two imaging techniques were calculated using a mixed-effects binary regression model. results: data from 12 studies were extracted and included in the meta-analysis (7361 patients, 77.1% male). pooled sensitivity and specificity of ultrasonography in detection of hemothorax were 0.67 (95% ci: 0.41-0.86; i2= 68.38, p<0.001) and 0.99 (95% ci: 0.95-1.0; i2= 88.16, p<0.001), respectively. these measures for radiography were 0.54 (95% ci: 0.33-0.75; i2= 92.85, p<0.001) and 0.99 (95% ci: 0.94-1.0; i2= 99.22, p<0.001), respectively. subgroup analysis found operator of the ultrasonography device, frequency of the transducer and sample size to be important sources of heterogeneity of included studies. conclusion: the results of this study showed that although the sensitivity of ultrasonography in detection of hemothorax is relatively higher than radiography, but it is still at a moderate level (0.67%). the specificity of both imaging modalities were found to be at an excellent level in this regard. the screening characteristics of ultrasonography was found to be influenced of the operator and frequency of transducer. keywords: hemothorax; ultrasonography; radiography; diagnostic tests, routine cite this article as: rahimi-movaghar v, yousefifard m, ghelichkhani p, et al. application of ultrasonography and radiography in detection of hemothorax: a systematic review and meta-analysis. emergency. 2016; 4(3):116-126. introduction: hest traumas are one of the most important causes of mortality in the fourth decade of life (1, 2). 25% of trauma mortalities are due to these injuries (3). in this regard, imaging techniques play a vital role in management of these patients. although some thoracic traumas are treated according to clinical findings of the patient before performing any imaging studies, but in many cases application of various imaging modalities such as computed tomography (ct) scan, plain chest xray (cxr) and ultrasonography are necessary. among these modalities, ct scan is the gold standard for identification of intra thoracic injuries following trauma with a significantly high diagnostic value for occult and soft tissue injuries (4-9). however, limited availability of ct scan in all medical centers, limitations in patient transfer c this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 117 emergency (2016); 4 (3): 116-126 to radiology department and radiation exposure led the researchers to look for other diagnostic tools (10). cxr is the first diagnostic test for screening of thoracic traumas but the limitations of supine radiography in some traumatic injuries such as pneumothorax is confirmed in various studies (11, 12). moreover, low diagnostic yield of routine chest radiography in patients with thoracic injuries encouraged the researchers to search for alternative imaging techniques (11-14). accordingly, in recent years scoring systems such as thoracic injury rule out criteria (tirc) and national emergency x-radiography utilization study (nexus) have been developed to lower the burden of unnecessary imaging studies (15, 16). major attention has recently been drawn to ultrasonography as a quick screening tool with minimum complications (17). it has shown to have superior diagnostic value in detection of thoracic traumatic injuries compared to chest radiography (18-22). however, diagnostic accuracy of ultrasonography is highly dependent on the skills of the operator and is usually not reliable in detection of injuries without bleeding or free fluid (23-25). hemothorax is one the traumatic thoracic injuries caused by accumulation of blood in pleural cavity. this lesion along with pneumothorax is present in 83% of thoracic traumas (26). however, detection of this complication via chest radiography is not possible unless the volume of hemothorax exceeds 175 milliliters (27). moreover, the diagnostic value of ultrasonography for hemothorax is still a matter of debate as well (18, 19, 28, 29). recently multiple systematic reviews have been published to evaluate the diagnostic value of ultrasonography and chest radiography in detection of thoracic traumas, but almost all of them have assessed pneumothorax. these reviews showed a higher sensitivity of ultrasonography in identification of pneumothorax compared to chest radiography (29, 30). none of these surveys has taken a meta-analytic approach towards assessing diagnostic value of these imaging modalities in detection of hemothorax. therefore, the present study figure 1: flowchart of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahimi-movaghar et al 118 t a b le 1 : c h a re ct e ri st ic s o f in cl u d e d s tu d ie s s tu d y n o . o f p a ti e n t (+ / )1 a g e 2 ( y e a r s ) m a le (% ) r e fe r e n c e / in d e x t r a n s d u c e r / o p e r a to r s a m p li n g w e a k n e s s e s m a 1 9 9 7 (2 7 ) 2 6 / 2 1 4 n r n r c t / u s , c x r 3 .5 -t o 2 .5 -m h z / e p c o n se cu ti v e r e tr o sp e ct iv e d e si g n a b b o u d 2 0 0 3 ( 2 8 ) 1 4 / 1 2 6 3 8 ( 5 – 8 9 ) n r c t / u s 3 .7 5 m h z / e p c o n v e n ie n c e t im e i n te rv a l b e tw e e n u s a n d c t sc a n w a s v a ri e d ; b li n d in g w a s n o t p e rf o rm e d b r o o k s 2 0 0 4 (1 8 ) 1 2 / 4 9 n r n r c t / u s 4 to 2 -m h z / e p c o n v e n ie n c e s m a ll s a m p le s iz e ; p o ss ib il it y o f se le ct io n b ia s t r a u b 2 0 0 7 (3 1 ) 1 6 / 1 2 5 4 7 ( 1 8 -8 9 ) 7 5 c t / c x r n a / r a d io lo g is t c o n v e n ie n c e r e tr o sp e ct iv e d e si g n p o ss ib il it y o f se le ct io n b ia s h y a c in th e 2 0 1 2 ( 1 9 ) 3 5 / 2 0 2 3 9 ( 2 2 -5 1 ) 8 2 c t / u s 5 to 2 -m h z / e p c o n se cu ti v e p o ss ib il it y o f se le ct io n b ia s p o v e d a 2 0 1 2 (3 2 ) 4 7 / 2 1 3 9 ( 1 6 -7 0 ) 8 9 .7 s u rg e ry / u s 3 .7 5 m h z / r a d io lo g is t c o n v e n ie n c e p o ss ib il it y o f se le ct io n b ia s b ła s iń s k a 2 0 1 3 ( 3 3 ) 2 4 / 3 6 n r n r c t / c x r n a / r a d io lo g is t c o n se cu ti v e l o w s a m p le s iz e u z 2 0 1 3 (3 4 ) 2 1 / 8 6 3 7 ( 1 9 .8 ) 8 0 .4 c t / u s 1 0 -t o 5 -m h z / r a d io lo g is t c o n se cu ti v e l o w s a m p le s iz e c h a r d o li 2 0 1 3 ( 3 5 ) 1 4 / 1 8 6 3 8 ( 1 6 -9 0 ) 8 4 c t / c x r n a / e p c o n v e n ie n c e t h e i n te rp re ta ti o n o f th e c x r a n d c t w e re n o t in b li n d f a sh io n p o ss ib le s e le ct io n b ia s l e b la n c 2 0 1 4 ( 3 6 ) 1 9 / 2 6 3 6 ( 1 5 -5 6 ) 7 1 c t / u s , c x r 5 -t o 1 -m h z / in te n si v is t c o n v e n ie n c e l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s l a n g d o r f 2 0 1 5 ( 3 7 ) 2 3 0 / 5 6 8 2 ≥ 1 5 5 7 .4 c t / c x r n a / r a d io lo g is t c o n v e n ie n c e p o ss ib il it y o f se le ct io n b ia s v a ri a ti o n i n t im in g o f c t a n d c x r v a fa e i 2 0 1 5 (3 8 ) 2 9 / 1 2 3 3 1 ( 4 -6 7 ) 7 7 .6 c t / u s , c x r 3 .5 -t o 7 -m h z / e p c o n v e n ie n c e p o ss ib il it y o f se le ct io n b ia s 1 , ( + / ): n u m b e r o f p a ti e n t w it h h e m o th o ra x / n u m b e r o f p a ti e n t w it h o u t h e m o th o ra x ; 2 , n u m b e r a re p re se n te d a s m e a n ± s ta n d a rd d e v ia ti o n o r (r a n g e ). c t : c o m p u te d t o m o g ra p h y ; c x r : c h e st r a d io g ra p h y ; e p : e m e rg e n cy p h y si ci a n ; n a : n o t a p p li ca b le ; n r : n o t r e p o rt e d ; u s : u lt ra so n o g ra p h y . this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 119 emergency (2016); 4 (3): 116-126 aimed to evaluate the diagnostic accuracy of chest ultrasonography and radiography in detection of hemothorax through a systematic review of available literature and meta-analysis. methods: search strategy and selection criteria two independent reviewer (m.y, p.g) performed an extended systematic search in databases of medline (via pubmed), embase, isi web of knowledge, scopus, cochrane library, and proquest. we screened google scholar for further studies. the objective was to find surveys evaluating the diagnostic accuracy of ultrasonography or chest radiography in detection of hemothorax. keywords were chosen according to medical subject heading (mesh) terms and emtree. similar keywords were used for search in other databases. these keywords were terms related to ultrasonography and radiography including “ultrasonography” or “sonography” or “ultrasound” or “chest film” or “chest radiograph” combined with hemothorax related terms including “hemothorax” or “haemothorax” or “haemorrhagic pleural effusion”. in order to find further studies or unpublished surveys, hand-search was performed on the list of bibliography of relevant studies and the authors were contacted in cases where the data could not be extracted from the survey. only the original articles and the surveys conducted on human subjects were included. review and editorial articles, case reports, letters to editors, poster presentations, and meeting abstracts were excluded. studies were included only if they presented an evaluation of the diagnostic value of ultrasonography or chest radiography in hemothorax detection. other inclusion criteria were as follows: confirmation of injury via ct scan or surgery, performance of radiography or ultrasonography for all patients, presentation of true positive, true negative, false positive, and false negative cases (in the article, through contacting the authors, or using webbased calculators). no time or language limitations were applied. both retrospective and prospective studies were included. data extraction two of the authors (m.y, p.g) independently worked on summarizing the data including assessment of quality of studies, information related to the subjects (age, gender, the number of patients with/without hemothorax, the etiology of hemothorax), the characteristics of ultrasonography device (transducer, frequency), operators and the physicians in charge of interpreting the imaging, blinding status, sampling method (consecutive, convenience), study design (retrospective, prospective), reference test, and the number of true positive, false positive, true negative, and false negative cases. disagreements were discussed with the third author (m.h) and a solution was proposed. in cases of data inaccessibility, the corresponding authors of the articles were contacted. data presented as charts were extracted via the method proposed by sistrom and mergo (39). in cases where only the sensitivity and specificity were presented in the article, reliable web-based programs were used to calculate the number of true positive, false positive, true negative and false negative cases. quality of the studies were evaluated according to the quality assessment of diagnostic accuracy studies (quadas2) guideline (40). assessment was performed based on the criteria established for designing a diagnostic survey considering various biases including selection, performance, recording and reporting bias. statistical analysis analysis was performed via stata 11.0 statistical software through midas module. the number of false positive, false negative, true positive and true negative cases were recorded. then, pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of chest ultrasonography and radiography in detection of hemothorax were calculated with 95% confidence interval (95% ci). in cases of data presented for each hemithorax separately, we also included the information, separately. in the present study, mixed-effects binary regression model, a type of random effect model, was used because of the presence of significant heterogeneity between the studies. heterogeneity was assessed through application of i2 and χ2 tests. a p value of less than 0.1 along with an i2 greater than 50% were considered as positive heterogeneity (41). to identify the source of heterogeneity, subgroup analysis was carried out using a bivariate mixed-effects binary regression model. subgroup analyses were performed according to sampling method (consecutive / convenience), operator of the ultrasonography device (emergency physician/ other specialists) or the interpreting physician of cxr, the frequency of ultrasonography transducer (1-5 mhz/ 5-10 mhz) and sample size (less than 100 patients/ more than 100 patients). results: study characteristics in literature review, 178 potentially relevant studies were identified, of which 37 met the inclusion criteria. eventually 12 surveys were included in final meta-analysis (18, 19, 27, 28, 31-38) (figure 1). data on 7361 trauma patients including 487 with hemothorax and 6874 without were extracted (77.1% male). table 1 summarizes the baseline characteristics of included studies. diagnostic accuracy of ultrasonography and radiography were evaluated simultaneously in three studies (27, 36, 38), whereas the accuracy of ultrasonography and radiography were assessed individually in five this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahimi-movaghar et al 120 (18, 19, 28, 32, 34) and four (31, 33, 35, 37) surveys, respectively. significant heterogeneity was observed between the studies (p<0.001). no publication bias was found (figure 2). meta-analysis ultrasonography area under the curve of summary receiver operative curves (sroc) for ultrasonography in detection of hemothorax was 0.97 (95% ci, 0.95-0.98) (figure 3-a). its pooled sensitivity and specificity in detection of hemothorax were 0.67 (95% ci: 0.41-0.86; i2= 68.38, p<0.001) and 0.99 (95% ci: 0.95-1.0; i2= 88.16, p<0.001), respectively. in addition, positive and negative likelihood ratios were computed to be 52.88 (95% ci: 9.87-283.23; i2= 80.61, p<0.001) and 0.33 (95% ci: 0.16-0.68; i2= 95.66, p<0.001), respectively (figure 4). subgroup analysis found sampling method (consecutive/ convenience), operator (emergency physician/ other specialists), frequency of the transducer (1-5 mhz/ 5-10 mhz), and sample size (less than 100 patients/ more than 100 patients) to be important sources of heterogeneity among studies. sensitivity of the surveys with consecutive sampling methods were significantly higher than the other studies (0.76 vs. 0.61), but their specificity did not differ considerably (1.0 vs. 0.97). moreover the sensitivity of ultrasonography in detection of hemothorax was found to be significantly higher when the procedure was performed via an emergency physician (0.70 vs. 0.62) or using a 5-10 mhz transducer (0.75 vs. 0.64) (table 2). radiography as presented in figure 3-b, area under the sroc curve for radiography was 0.92 (95% ci: 0.89-0.94). pooled sensitivity and specificity of this modality in detection of hemothorax were 0.54 (95% ci: 0.33-0.75; i2= 92.85, p<0.001) and 0.99 (95% ci: 0.94-1.0; i2= 99.22, p<0.001), respectively. its positive and negative likelihood ratios were also 46.01 (95% ci: 10.17-208.14; i2= 96.10, p<0.001) and 0.46 (95% ci: 0.29-0.75; i2= 95.66, p<0.001), respectively (figure 5). subgroup analysis showed that sampling method (consecutive / convenience), the interpreting physician (emergency physician/ other specialists), and sample size (less than 100 patients/ more than 100 patients) were important sources of heterogeneity between the studies. sensitivity of radiography was significantly higher in surveys with consecutive sampling methods (0.61 vs. 0.51) and with sample sizes of less than 100 patients (0.69 vs.0.46). discussion: sonography, as one of the most available screening tools in emergency settings, is useful for various clinical applications but its diagnostic value in traumatic thoracic injuries is still a controversial subject. the present study is the first to conduct a systematic review with meta-analytic approach on one of the most important thoracic traumas. the results of this study illustrated the relatively higher sensitivity of ultrasonography in this regard, but it is still at a moderate level. the specificity and positive likelihood ratios calculated for both of these modalities were same and excellent. the results of subgroup analysis showed that the sensitivity of ultrasonography was influenced by the operator of the ultrasound device and frequency of transducer but the specificity of this modality is not affected by them. accordingly, as ultrasonography performed by an emergency physician has a higher diagnostic value compared to other physicians. this finding might be due to awareness of the emergency physician about the clinical condition of the patient. although in 8 studies the operators were blinded and in the other 4 the setting was not mentioned, a complete unawareness of the emergency physician about the patients’ clinical condition seems unlikely. since these physicians are the first line of the medical team responsible for treatment of trauma patients, based on their experience they might suspect the presence of hemothorax according to the history and clinical findings of the subjects and consequently pay much more attention to find sonographic evidence of this complication. the diagnostic value of chest radiography in detection of hemothorax is neither affected by the operator nor by the interpreting physician, since the physician or the radiologist is not in direct contact with the patients when interpreting their radiographs. ebrahimi et al. (29) found no significant relation between frequency of transducer and detection of pneumothorax but the present survey yielded opposite results regarding detection of hemothorax. this might be due to the fact that the sound wave emitted from the transducer easily moves through fluids (high penetrating power in fluids), since the amount of energy absorbed by the fluids is very low. therefore, ultrasonography with higher frequencies is able to produce clearer images with higher resolutions (42), an event that does not occur in pneumothorax because propagation of the sound wave through the air is associated with loss of energy and so pictures with higher resolutions are not necessarily yielded with higher frequencies. the minimum amount of fluid that can be detected by each of these modalities is different, 175 milliliters for radiography and only 20 milliliters for ultrasonography (27). according to subgroup analysis, diagnostic accuracy of radiography in detection of hemothorax is influenced by the sample size of the survey. the results showed that in the studies with sample sizes of less than 100 patients, the sensitivity of radiography was reported to be higher. this finding could be due to probable selection bias in studies with smaller sample sizes, which might have led this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 121 emergency (2016); 4 (3): 116-126 t a b le 2 : s u b g ro u p a n a ly si s o f d ia g n o st ic a cc u ra cy f o r ch e st r a d io g ra p h y a n d u lt ra so n o g ra p h y i n d e te ct io n o f h e m o th o ra x c o v a r ia te n o . o f s tu d ie s b iv a r ia te r a n d o m -e ff e c t m o d e l s e n s it iv it y ( 9 5 % c i) p s p e c if ic it y ( 9 5 % c i) p h e te r o g e n e it y , i2 p * u lt r a s o n o g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 3 0 .7 6 ( 0 .4 5 -1 .0 0 ) 0 .5 6 1 .0 0 ( 0 .9 9 -1 .0 0 ) 0 .8 6 1 0 .0 0 % 0 .3 3 c o n v e n ie n c e 5 0 .6 1 ( 0 .3 1 -0 .9 2 ) 0 .9 7 ( 0 .9 3 -1 .0 0 ) o p e r a to r e m e rg e n cy p h y si ci a n 5 0 .7 0 ( 0 .4 2 -0 .9 9 ) 0 .6 8 0 .9 9 ( 0 .9 8 -1 .0 0 ) 0 .0 2 0 .0 0 % 0 .5 9 o th e r p h y si ci a n 3 0 .6 2 ( 0 .2 3 -1 .0 0 ) 0 .9 7 ( 0 .9 0 -1 .0 0 ) s a m p le s iz e < 1 0 0 5 0 .7 0 ( 0 .4 1 -0 .9 8 ) 0 .7 2 0 .9 9 ( 0 .9 7 -1 .0 0 ) 0 .0 8 0 .0 0 % 0 .7 4 ≥ 1 0 0 3 0 .6 3 ( 0 .2 4 -1 .0 0 ) 0 .9 8 ( 0 .9 5 -1 .0 0 ) f r e q u e n c y o f tr a n s d u c e r 1 -5 m h z 5 0 .6 4 ( 0 .3 7 -0 .9 2 ) 0 .5 5 0 .9 9 ( 0 .9 7 -1 .0 0 ) 0 .1 2 0 .0 0 % 0 .9 4 5 -1 0 m h z 3 0 .7 5 ( 0 .3 7 -1 .0 0 ) 0 .9 9 ( 0 .9 5 -1 .0 0 ) r a d io g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 3 0 .6 1 ( 0 .2 4 -0 .9 8 ) 0 .6 5 0 .9 8 ( 0 .9 4 -1 .0 0 ) 0 .0 3 0 .0 0 % 0 .8 8 c o n v e n ie n c e 6 0 .5 1 ( 0 .2 3 -0 .7 8 ) 0 .9 9 ( 0 .9 7 -1 .0 0 ) o p e r a to r e m e rg e n cy p h y si ci a n 5 0 .5 4 ( 0 .2 4 -0 .8 4 ) 0 .9 6 0 .9 9 ( 0 .9 7 -1 .0 0 ) 0 .0 7 0 .0 0 % 0 .9 9 o th e r p h y si ci a n 4 0 .5 5 ( 0 .2 2 -0 .8 7 ) 0 .9 9 ( 0 .9 6 -1 .0 0 ) s a m p le s iz e < 1 0 0 3 0 .6 9 ( 0 .3 8 -1 .0 0 ) 0 .3 2 0 .9 4 ( 0 .8 1 -1 .0 0 ) 0 .3 8 0 .0 0 % 0 .9 9 ≥ 1 0 0 6 0 .4 6 ( 0 .2 1 -0 .7 2 ) 0 .9 9 ( 0 .9 9 -1 .0 0 ) *, p v a lu e < 0 .1 w a s co n si d e re d a s si g n if ic a n t fo r h e te ro g e n e it y ; c i: c o n fi d e n c e i n te rv a l. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahimi-movaghar et al 122 to evaluation of patients with greater volumes of free fluids that increases their chance of detection via radiography (43). limitations since all included studies were observational precise evaluation of causal relationships was not possible. the skills of the operator in performing ultrasonography were not considered in any of these surveys and the effect of this bias is not clear in the present study. finally a significant heterogeneity was found between the surveys whose effects were tried to be minimized by application of mixed random effect model and subgroup analysis. conclusion: the results of this study showed that although the sensitivity of ultrasonography in detection of hemothorax is relatively higher than radiography, but it is still at a moderate level (0.67%). the specificity of both imaging modalities were found to be at an excellent level in this regard. the screening characteristics of ultrasonography was found to be influenced of the operator and frequency of transducer. acknowledgments: none conflict of interest: none funding support: this research has been supported by tehran university of medical sciences & health services grant number: 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radiography in initial evaluation of chest trauma patients. emergency. 2015;3:[in press]. 39. sistrom cl, mergo pj. a simple method for obtaining original data from published graphs and plots. am j roentgenol. 2000;174(5):1241-4. 40. whiting pf, rutjes aw, westwood me, et al. quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies. ann intern med. 2011;155(8):529-36. 41. higgins jp, thompson sg, deeks jj, altman dg. measuring inconsistency in meta-analyses. bmj. 2003;327(7414):557. 42. majumdar s, kumar ps, pandit a. effect of liquid-phase properties on ultrasound intensity and cavitational activity. ultrason sonochem. 1998;5(3):113-8. 43. deeks jj, macaskill p, irwig l. the performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. j clin epidemiol. 2005;58(9):882-93. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahimi-movaghar et al 124 a b figure 2: deeks’ funnel plot asymmetry test for assessment of publication bias. p values < 0.05 were considered as significant. ultrasonography (a); radiography (b). ess: effective sample sizes. a b figure 3: summary receiver operative curves (sroc) for ultrasound (a) and chest radiography (b) in detection of hemothorax. auc: area under the curve; sens: sensitivity; spec: specificity. 1 2 3 4 5 6 7 8 .1 .12 .14 .16 .18 .2 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.56 1 2 3 4 5 6 7 8 9 0 .05 .1 .15 1 / ro o t( e s s ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.10 1 2 3 4 5 6 7 8 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.67 [0.41 0.86] spec = 0.99 [0.95 1.00] sroc curve auc = 0.97 [0.95 0.98] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours 1 2 3 4 5 6 7 8 9 0.0 0.5 1.0 s e n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.54 [0.33 0.75] spec = 0.99 [0.94 1.00] sroc curve auc = 0.92 [0.89 0.94] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 125 emergency (2016); 4 (3): 116-126 a b figure 4: forest plot of screening performance characteristics of chest ultrasonography in detection of hemothorax. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q = 68.38, df = 7.00, p = 0.00 i2 = 89.76 [84.11 95.42] 0.67[0.41 0.86] 0.76 [0.56 0.90] 0.37 [0.22 0.54] 0.71 [0.48 0.89] 0.72 [0.57 0.84] 0.37 [0.21 0.55] 0.92 [0.64 1.00] 0.13 [0.02 0.38] 0.96 [0.80 1.00]0.96 [0.80 1.00] author / year combined vafaei 2015 leblanc 2014 uz 2013 poveda 2012 hyacinthe 2012 brooks 2004 abboud 2003 ma 1997 0.0 1.0 specificity (95% ci) q = 59.13, df = 7.00, p = 0.00 i2 = 88.16 [81.35 94.97] 0.99[0.95 1.00] 0.96 [0.91 0.99] 0.75 [0.35 0.97] 1.00 [0.96 1.00] 0.95 [0.76 1.00] 0.97 [0.94 0.99] 1.00 [0.93 1.00] 0.98 [0.94 1.00] 1.00 [0.98 1.00]1.00 [0.98 1.00] author / year combined vafaei 2015 leblanc 2014 uz 2013 poveda 2012 hyacinthe 2012 brooks 2004 abboud 2003 ma 1997 0.3 1.0 dlr positive (95% ci) q = 57.09, df = 7.00, p = 0.00 i2 = 80.61 [80.61 94.86] 52.88[9.87 283.23] 18.66 [7.72 45.12] 1.47 [0.41 5.25] 122.59 [7.63 1000] 15.19 [2.23 103.71] 12.38 [5.04 30.40] 89.29 [5.63 1000] 7.87 [1.19 52.11] 406.11 [25.45 1000]406.11 [25.45 1000] author / year combined vafaei 2015 leblanc 2014 uz 2013 poveda 2012 hyacinthe 2012 brooks 2004 abboud 2003 ma 1997 0.4 1000.0 dlr negative (95% ci) q =161.26, df = 7.00, p = 0.00 i2 = 95.66 [93.80 97.52] 0.33[0.16 0.68] 0.25 [0.13 0.48] 0.84 [0.53 1.00] 0.30 [0.16 0.57] 0.29 [0.18 0.47] 0.65 [0.50 0.84] 0.11 [0.02 0.49] 0.89 [0.74 1.00] 0.06 [0.01 0.26]0.06 [0.01 0.26] author / year combined vafaei 2015 leblanc 2014 uz 2013 poveda 2012 hyacinthe 2012 brooks 2004 abboud 2003 ma 1997 0 1 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahimi-movaghar et al 126 a b figure 5: forest plot of screening performance characteristics of chest radiography in detection of hemothorax. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q =111.84, df = 8.00, p = 0.00 i2 = 92.85 [89.51 96.18] 0.54[0.32 0.75] 0.20 [0.15 0.26] 0.59 [0.39 0.76] 0.79 [0.54 0.94] 0.21 [0.05 0.51] 0.58 [0.37 0.78] 0.17 [0.07 0.34] 0.63 [0.35 0.85] 0.67 [0.35 0.90] 0.96 [0.80 1.00]0.96 [0.80 1.00] author / year combined langdorf 2015 vafaei 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 traub 2007 brooks 2004 ma 1997 0.0 1.0 specificity (95% ci) q =1019.98, df = 8.00, p = 0.00 i2 = 99.22 [99.04 99.40] 0.99[0.94 1.00] 1.00 [1.00 1.00] 0.95 [0.90 0.98] 0.62 [0.41 0.80] 1.00 [0.98 1.00] 0.97 [0.86 1.00] 0.94 [0.90 0.97] 0.99 [0.96 1.00] 0.98 [0.89 1.00] 1.00 [0.97 1.00]1.00 [0.97 1.00] author / year combined langdorf 2015 vafaei 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 traub 2007 brooks 2004 ma 1997 0.4 1.0 dlr positive (95% ci) q =277.37, df = 8.00, p = 0.00 i2 = 96.10 [96.10 98.13] 46.01[10.17 208.14] 536.60 [74.34 1000] 12.02 [5.20 27.79] 2.05 [1.20 3.52] 87.27 [4.72 1000] 21.58 [3.03 153.63] 2.89 [1.16 7.18] 78.75 [10.78 575.36] 33.33 [4.60 241.69] 206.73 [29.21 1000]206.73 [29.21 1000] author / year combined langdorf 2015 vafaei 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 traub 2007 brooks 2004 ma 1997 1.2 1000.0 dlr negative (95% ci) q =149.20, df = 8.00, p = 0.00 i2 = 94.64 [92.34 96.93] 0.46[0.29 0.75] 0.80 [0.75 0.85] 0.44 [0.28 0.67] 0.34 [0.14 0.86] 0.77 [0.58 1.00] 0.43 [0.27 0.69] 0.88 [0.75 1.00] 0.38 [0.20 0.71] 0.34 [0.15 0.76] 0.04 [0.01 0.26]0.04 [0.01 0.26] author / year combined langdorf 2015 vafaei 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 traub 2007 brooks 2004 ma 1997 0 1 archives of academic emergency medicine. 2022; 10(1): e57 or i g i n a l re s e a rc h effect of interposed abdominal compression on cardiopulmonary resuscitation outcomes; a randomized clinical trial atefeh ghanbari khanghah1, mohammad taghi moghadamnia2, latif panahi3∗, somaye pouy4, marjan aghajani nargesi5, ehsan kazemnezhad leyli6 1. professor, social determinants of health research center (sdhrc), department of nursing and midwifery (medicalsurgical), guilan university of medical sciences, rasht, iran. 2. department of medical surgical nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 3. master student of emergency nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 4. phd candidate in nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 5. clinical research development unit of razi hospital, department of emergency medicine, school of medicine, guilan university of medical sciences, rasht, iran. 6. associate professor, department of biostatistics, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. received: april 2022; accepted: may 2022; published online: 16 july 2022 abstract: introduction: standard cardiopulmonary resuscitation (std-cpr) is successful in only 10-15% of cases in emergency department (ed). this study aimed to determine the effect of interposed abdominal compression (iac) during resuscitation on outcomes of ed cardiac arrests. methods: in this randomized clinical trial study, nontrauma patients aged 18-85 years, patients with in-hospital cardiac arrest hospitalized in the ed were randomly assigned into two either std-cpr or iac-cpr group on a 1:1 basis and using computer-generated random numbers. participants in the intervention group, received abdominal compression during the diastole phase of stdcpr. the rate of return of spontaneous circulation (rosc), heart rate (hr), respiratory rate (rr), arterial blood gas (abg) indicators, and survival rate were compared between the two groups. results: ninety patients were enrolled (45 in each group). there were no differences between the two groups regarding age (p = 0.76), sex (p = 0.39), employment status (p = 0.62) and charlson comorbidity scale (p = 0.46). abdominal compression had a positive effect on heart rate (p < 0.001), mean arterial pressure (p = 0.003), arterial blood oxygen pressure (p = 0.001), and arterial blood carbon dioxide pressure (p = 0.001) as well as a negative effect on arterial blood oxygen saturation (p = 0.029) 30 minutes after resuscitation. out of the 90 cpr cases, 8 (17.7%) cases in intervention group and 8 (17.7%) cases in control group were successful, among which all of the 8 patients in the intervention group and 5 of the patients in the control group had been discharged from hospital without any complications. conclusion: the results showed that abdominal compression during cpr can improve resuscitation outcomes in patients with cardiac arrest. therefore, in order to use this technique, further research is recommended. keywords: heart arrest; cardiopulmonary resuscitation; treatment outcome; clinical trial cite this article as: ghanbari khanghah a, moghadamnia mt, panahi l, pouy s, aghajani nargesi m, kazemnezhad leyli e. effect of interposed abdominal compression on cardiopulmonary resuscitation outcomes; a randomized clinical trial . arch acad emerg med. 2022; 10(1): e57. https://doi.org/10.22037/aaem.v10i1.1678. ∗corresponding author: latif panahi; master student of emergency nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. email: latif_p2020@yahoo.com; tel: +98 (922) 4833167, orcid: http://orcid.org/0000-0001-5157-2613. 1. introduction sudden cardiac arrest is one of the main causes of death around the world (1, 2). according to global statistics, in the united states, about 350,700 adults over the age of 18 experience in-hospital cardiac arrest each year (3). standard cardiopulmonary resuscitation (std-cpr) is one of the meththis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ghanbari khanghah et al. 2 ods used to save the lives of these people. std-cpr involves applying pressure to the chest of a patient with cardiac arrest and ventilation with an ambu bag, which causes an increase in the patient’s probability of survival before performing advanced life-saving procedures (4, 5). according to the latest revision of the american heart association (aha) guidelines, rapid and effective chest massage is a key component of stdcpr (6, 7). but chest massage is less successful in some patients and in certain conditions, such as patients with pneumothorax or chest trauma, and other alternative methods should be used (8, 9). according to conducted studies, it has been found that although std-cpr is widely used, the survival rate of patients undergoing this method is not completely desirable (3). also, based on a study in iran, it has been found that following std-cpr, the mortality rate is over 90% and the discharge rate from hospital is less than 7% (10). for reasons such as presence of an underlying disease, patient’s age, or delay in starting cpr, the final result of stdcpr may not be desirable. therefore, it may be necessary to use more effective and alternative methods for resuscitation in some patients (10). interposed abdominal compression cpr (iac-cpr) is one of the methods that may be able to make up for existing std-cpr defects (11-13). some clinical studies have reported that using iac-cpr for patients with cardiopulmonary arrest is more effective than std-cpr (8, 9, 14). on the other hand, a number of studies have shown that there is no difference between these two techniques regarding patient consequences and conducting more research is required (10, 15). according to the aha guidelines for cpr and emergency cardiovascular care, iac-cpr can be an effective method of cpr when staff are adequately trained. the level of evidence for iac-cpr is divided as class iib13, which means that although using this technique is not certainly recommended, further research is suggested due to many benefits of iaccpr (15). the current study has been conducted with the purpose of determining the effect of interposed abdominal compression on outcome of cpr for patients with cardiac arrest in emergency department (ed). 2. methods 2.1. study design and setting this is a two-group randomized clinical trial, which was conducted from june 2021 to may 2022 on patients with cardiac arrest, referring to razi hospital in rasht, iran. before selecting patients to enter the study and due to the emergency nature of cpr, the necessary explanations were given to the patient’s family members and informed consent was obtained. all patients with cardiopulmonary arrest were transferred to the resuscitation room of ed and all medical procedures were performed for them in this room. our data collection was done in this room, too. this research has been approved by the ethics committee of guilan university of medical sciences (ethics code: ir.gums.rec.1399.665) and it complies with the statements of the declaration of helsinki. also, the trial has been registered in the iranian registry of clinical trials (code: irct20080901001174n14). 2.2. participants all adult patients aged 18-85 years with in-hospital cardiac arrest in ed were enrolled in this study. inclusion criteria were non-trauma patients hospitalized in the ed who had in-hospital cardiac arrest in the presence of a nurse and their cardiopulmonary arrest was confirmed by a doctor and the presence of a resuscitation team including nurses, anesthesiologists, emergency medicine specialists, and the main researcher after announcing cpr code. exclusion criteria were liver cirrhosis, abdominal surgery in the past two weeks, active gastrointestinal bleeding based on nurse and physician’s explanations or report of patient’s family, history of pulmonary embolism, abdominal aortic aneurysm, significant abdominal ascites, abdominal cirrhosis, and a history of coagulation disorders. our eligibility criteria were defined according to previous studies. it should be noted that our methods did not change after initiation of trial. the patient enrollment process is shown in figure 1. according to studies by reynolds and zhou (16, 17) and considering the α = 0.05, and power = 80% the sample size was calculated as 45 people in each group. 2.3. study protocol eligible patients were randomly assigned to either std-cpr or iac-cpr group on a 1:1 basis. randomization of patients into two groups was done using a computer-generated random allocation sequence. the co-researcher (s.p) enrolled patients in the study and allocated patients to either group according to the random allocation sequence. when a cardiac arrest happened, a code (99) was announced and the resuscitation team was notified by pocket beeper. the resuscitation team included two nurses, an anesthesiology nurse, and an emergency medicine physician. all of patients underwent resuscitation based on aha2020 advanced cardiac life support protocol. chest compression was performed at a rate of 100 times per minute at a depth of 5 cm and ventilation rate was 8-10 times per minute. cardiac arrest was confirmed by physician and endotracheal intubation was performed as soon as possible. the intervention group received std-cpr plus iac-cpr and the control group received stdcpr only. in patients who received iac-cpr, abdominal compression was performed with open hands, fused together in center of abdomen between the xiphoid and the umbilicus during the relaxation phase of chest compression. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e57 depth, rhythm, and rate of abdominal compressions were similar to chest compressions and force on the abdomen was maintained until the beginning of next chest compression. we used a bag-valve-mask apparatus attached to the endotracheal tube and performed ventilation at a rate of 8-10 breaths/minute. oxygen was delivered at 100% fio2 in both groups. during resuscitation, 1 mg of epinephrine was injected intravenously every 3-5 minutes and other drugs were injected as needed based on the aha2020 guideline (such as amiodarone or lidocaine, atropine, epinephrine) (6). in compliance with aha guidelines, termination of cpr was considered with the appearance of an autonomous carotid pulse, moist facial complexion, the appearance of autonomous respiration, and shrinking pupils and reappearance of a light reflex, or the appearance of eyeball motion and limb spasms (7). if after continued cpr for at least 30 minutes no carotid pulse or autonomous breathing was noted, cpr was terminated after obtaining informed consent from family members. all patients with successful cpr were followed for their 24hour survival. for evaluation of complications of iac-cpr, patients were followed for 24 hours and the presence of any abdominal pain, tenderness in abdomen, and need for abdominal surgery after cpr, which could be sings and symptom of internal bleeding, were assessed in these patients. also, all patients in both groups were monitored and assessed in terms of any complication such as rib fracture, arrythmia, or post-resuscitation syndrome. 2.4. data collection demographic (age, sex, body mass index (bmi), height, and weight) and clinical (charlson comorbidity index, underlying diseases) information of patients at the time of cardiac arrest were recorded. the charlson comorbidity index (cci) was used to examine the presence of comorbidities in patients. the cci assesses 19 diseases and conditions, and rates the probability of the patient’s mortality based on them. the scores obtained from cci can be adjusted with age, so that each decade of age (starting from the age of 50) is considered as an additional score. scores range from zero to 37 in case of age mismatch and from zero to 43 in case of age match. finally, the scores are ranked as four degrees of illness: zero, 1-2, 3-4 and 5, where a higher score indicates the presence of more comorbidities (18). primary outcome measured in this study was return of spontaneous circulation (rosc). rosc was defined as the presence of a palpable carotid arterial pulse and a systolic blood pressure above 80 mmhg for longer than 3 minutes. secondary outcomes were heart rate (hr), respiratory rate (rr), mean arterial pressure (map), peripheral capillary oxygen saturation (spo2), partial pressure of carbon dioxide (paco2) and potential of hydrogen (ph) of arterial blood gas (abg). all of the outcomes were measured in the intervention and control groups immediately and half an hour after the start of cpr. the presence of rosc was assessed based on the carotid pulse. the paco2, ph, and spo2 were measured via abg test. for abg test, one of co-researcher (s.p) took an arterial blood sample and sent it to laboratory department of hospital as soon as possible and they used medica easy blood gas analyzer for abg analysis. for calculating map of patients, we measured systolic and diastolic blood pressures of patients with a cuff that was attached to a monitor. then it was estimated using a formula in which the diastolic blood pressure is doubled and added to the systolic blood pressure and that composite sum is then divided by 3 (19). the heart rate and respiratory rate were measured by the monitoring device. it should be mentioned that all of the patients who received cpr, in either group, were monitored using omnicare monitoring device. before starting the study, monitoring and medica easy blood gas analyzer devices had been calibrated and approved by the medical engineering team of hospital. in addition, during cpr in both groups, the emergency medicine physician was present and in case of any problems such as presence of any signs of internal bleeding, abdominal pain or tenderness, organ injury or rib fracture, he immediately examined the patient and requested emergency surgical counseling. also, we followed survived patients after cpr and assessed the survival to hospital discharge in order to assess the long-term survival of patients with successful cpr in each group. all of the primary and secondary outcomes were measured and recorded by one of the co-researchers (s.p). 2.5. data analysis after entering data in the statistical package for the social sciences (spss) software (version 25.0, armonk, ny: ibmcorp.), data analysis was performed using descriptive statistics (mean, standard deviation, frequency) and inferential tests (independent t test, chi-square). the significance level of the tests was considered less than 0.05. 3. results 3.1. baseline characteristics initially, 105 patients with cardiac arrest were assessed for eligibility in the study. finally, 90 cardiac arrest victims were enrolled (50 male and 40 female) and allocated into iac-cpr or std-cpr (each group 45 patients) during the period of june 2021 to may 2022. out of the 90 cases, 74 (82.22%) of cpr attempts was unsuccessful and only 8 (17.77%) cases in each group had successful resuscitation (a total of 16 patients). the mean age of the patients in control and intervention this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ghanbari khanghah et al. 4 figure 1: patients’ enrollment and allocation. groups were 40.60±16.80 and 60.04±14.97 years, respectively (range=19-72 years; p = 0.76). the most common cause of cardiopulmonary arrest in both groups were cardiac, cerebrovascular accident (cva), and respiratory reasons. inhospital complications in both groups included: bruising and abrasions in the face and neck, airway injuries, rib fracture, sternal fracture, and pneumothoraxes. there were not any significant differences between the two groups regarding cause of cardiopulmonary arrest or in-hospital complications. the most common underlying diseases in both groups were hypertension (32.22%), diabetes (16.66%), and cva (14.44%). there were not significant differences between the groups regarding underlying disease. sex distribution was not different between the two groups (p = 0.396). bmi was not different between the two groups (p = 0.432). cci was not different between the two groups (p = 0.463). table 1 compares demographic and clinical characteristics between the two groups. 3.2. outcomes 3.2.1. rosc the number of patients who had rosc immediately after the start of resuscitation was zero in both groups (p = 0.999). comparison of rosc from immediately to half an hour after the start of resuscitation had a significant increase in both the intervention group (p < 0.001) and the control group (p < this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e57 table 1: comparing the baseline characteristics of patients between the two studied groups variable std-cpr (n=45) iac-cpr (n=45) p-value age (year) 40.60±16.80 60.04±14.97 0.916 * bmi (kg/m2) 25.2± 4.1 25.8± 3.6 0.432* height (cm) 167.01±5.1 166.12±6.2 0.674* weight (kg) 71.1±9.2 72.03±8.9 0.712* charlson comorbidity scale 3.13±2.25 3.49±2.35 0.463* sex male 27 (60.0) 23 (51.11) 0.396** female 18 (40.0) 22 (48.88) cause of cardiopulmonary arrest cardiac 24 (53.33) 20 (53.33) 0.912* cerebrovascular accident 6 (13.33) 8 (17.77) 0.916* respiratory 5 (11.11) 6 (13.33) 0.891* renal 4 (8.88) 5 (11.11) 0.456* cancer 3 (6.66) 3 (6.66) 0.876* bleeding 2 (4.44) 3 (6.66) 0.897* infection 1 (2.22) 0 (0.00) 0.345* in-hospital complications bruising and abrasions in face/neck 16 (35.55) 15 (33.33) 0.786* airway injuries 12 (26.66) 9 (22.22) 0.567* rib fracture 8 (17.77) 7 (15.55) 0.862* sternal fracture 3 (6.66) 2 (4.44) 0.457* pneumothoraxes 2 (4.44) 1 (2.22) 0.347* underlying disease hypertension 15 (33.33) 14 (31.11) 0.456** cancer 7 (15.55) 8 (17.77) 0.678** diabetes 7 (15.55) 6 (13.33) 0.377** mi 4 (8.88) 4 (8.88) 0.321** copd 4 (8.88) 4 (8.88) 0.561** renal failure 3 (6.66) 4 (8.88) 0.423** hepatitis 2 (4.44) 2 (4.44) 0.345** cva 2 (4.44) 3 (6.66) 0.423** asthma 1 (2.22) 0 (0.00) 0.781** data are presented as mean ± standard deviation or frequency (%). cpr: cardiopulmonary resuscitation; std-cpr= standard cpr; iac-cpr= interposed abdominal compression cpr; bmi= body mass index; copd = chronic obstructive pulmonary disease; cva = cerebral vascular accident; mi = myocardial infarction. * independent t test. ** chi-square 0.001) and in both groups, 8 patients (17.77%) had rosc (table 2). 3.2.2. vital signs after cpr, almost all patients in both groups had heart rate and map, but fewer patients in both groups had respiratory rate. patients in the iac-cpr group had higher heart rate and lower map compared to the std-cpr group. the two groups had the same mean respiratory rate immediately (p = 0.611) and half an hour (p = 0.476) after cpr. although the respiratory rate in the iac-cpr group increased slightly more than the std-cpr group, and the rate of increase was 0.31 ± 1.06 in the std-cpr group and 0.76± 33.40 in the iac-cpr group, the difference was not statistically significant (table 2). 3.2.3. change of blood gas measurements there was no significant difference in spo2 between control and intervention groups immediately (p = 0.887) and also half an hour (p = 0.292) after the start of cpr, but there was a significant increase in spo2 between these two times in both control (p < 0.001) and intervention (p < 0.001) groups. this increase was more in iac-cpr in comparison to stdcpr group. the mean pao2 was not significantly different between the two groups immediately after the start of cpr, but it was significantly different half an hour after the start of cpr. the rate of change in the control group was not significant for this variable from immediately to half an hour after cpr, but there was a significant increase in the intervention group (p <0.001). this increase was more in iac-cpr in comparison to std-cpr group. arterial blood ph was not significantly different between the two groups immediately after the start of cpr, but it was significantly different half an hour after the start of cpr (p <0.001). both groups had a significant decrease in ph from immediately to half an hour after the start of cpr (p <0.001), but the rate of decrease in arterial blood ph in the intervention group was greater than this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ghanbari khanghah et al. 6 table 2: comparing the vital signs and arterial blood gas parameters between the two groups at baseline and 30 minutes after cpr variable std-cpr (n=45) iac-cpr (n=45) p-value effect size heart rate (beat/minute) baseline 65.31±19.40 98.42±14.86 < 0.001 30 minutes after cpr 60.69±20.82 99.58±18.93 < 0.001 0.094 change from baseline -4.62±7.11 1.16±10.65 0.010 respiratory rate baseline 3.58±7.82 4.47±8.51 0.611 30 minutes after cpr 3.89±8.49 5.22±9.30 0.476 0.008 change from baseline 0.31±1.06 0.76±3.40 0.959 map baseline 51.04±11.61 65.60±8.17 < 0.001 30 minutes after cpr 48.24±10.41 63.87±8.56 < 0.001 0.009 change from baseline 2.80±5.81 1.73± 5.49 0.641 ph baseline 7.27±0.09 7.24±0.08 0.102 30 minutes after cpr 7.16±0.10 7/00±0.47 <0.001 0.037 change from baseline 0.11±0.06 -0.24± 0.47 <0.001 spo2 baseline 68.34±16.71 66.45±19.18 0.878 30 minutes after cpr 71.69±15.93 76.89±17.79 0.292 0.361 change from baseline 13.35±4.29 14.44±3.62 <0.001 pao2 baseline 55.76±38.91 55.43±25.65 0.373 30 minutes after cpr 59.21±38.92 68.71±26.16 0.002 0.361 change from baseline 3.45±7.52 13.28±3.45 <0.001 paco2 baseline 51.33±13.84 56.02± 10.99 0.106 30 minutes after cpr 51.33±13.21 51.80±10.96 0.932 0.383 change from baseline 0.01±2.85 4.22± 2.50 <0.001 data are presented as mean ±standard deviation; cpr: cardiopulmonary resuscitation; std-cpr= standard cpr; iac-cpr= interposed abdominal compression cpr; map=mean arterial pressure; ph= potential of hydrogen; spo2= peripheral capillary oxygen saturation; pao2= partial pressure of oxygen; paco2= partial pressure of carbon dioxide. the control group. the mean paco2 immediately after the start of cpr (p = 0.106) and half an hour after that (p = 0.932) was not significantly different between the two groups, but the changes in paco2 in the intervention group were greater than the control group (p <0.001). (table.2) 3.2.4. long-term outcomes after successful cpr, we followed survived patients (8 cases in intervention and 8 cases in control group) and all of the 8 patients in iac-cpr and 5 of the patients in std-cpr had long-term survival and were discharged from hospital without any complications such as dysrhythmia or cpr-related side effects, including fracture or internal bleeding. 4. discussion the quality of cpr, as assessed by appropriate cardiac output, is often low and less than desirable level (20). the amount of cardiac output after a desired std-cpr is usually more than 30% of the normal cardiac output, and coronary blood flow during cpr is often less than 35% of the normal coronary blood flow, because of different reasons (21). so, it is recommended to use alternative methods for cpr such as iac-cpr. the results of the current study showed that iac-cpr can improve cpr-related outcomes in patients with cardiopulmonary arrest. also, significant changes in arterial blood gas levels were observed in both groups and these outcomes were not affected by age, sex, and bmi. according to the results of the current study, no difference was found between the two groups regarding the number of people who had rosc, and in both groups, 8 people had rosc half an hour after the start of resuscitation. based on the study by movahedi et al., which was conducted for comparing the effect of std-cpr and iac-cpr on rosc and the amount of end-expiratory carbon dioxide in patients with in-hospital cardiopulmonary arrest, the results showed that rosc levels were significantly different between the two groups (10), which is not consistent with the present study. also, in the study by mateer et al., there was no significant difference in terms of rosc between the two groups (22), which is consistent with the current study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e57 in terms of respiratory rate, although its increase among patients in the intervention group was slightly greater than the control group, but they were not statistically significant. in the study by zhang et al., no significant difference was reported between the two groups (11), which is consistent with the findings of the present study. also, in the study by wang et al., it was found that iac-cpr increased the number of rr in patients with cardiopulmonary arrest (23), which is in line with the findings of the present study. considering that the rr in the intervention group increased more than the control group, it can be argued that in the iac-cpr method, applying intermittent pressure on the abdomen causes the diaphragm to move up and down, and the pressure in the chest changes, thus facilitating the entry and exit of air into the lungs. in this method, intermittent abdominal massage causes the diaphragm to move downward, allowing the lungs to expand, and the upward movement of the diaphragm also causes air to drain from the lungs. in terms of map, both groups had significant changes and these changes in the control group had a more decreasing course than the intervention group. however, this difference in decrease between the two groups was not statistically significant (p = 0.641). in the study by zhang et al., all patients and in both groups, map changes were negative, i.e., due to performing cpr in both groups, the amount of map was increased, but patients in the intervention group had lower map compared to the control group (p = 0.003), which is consistent with the findings of the current study. also, according to a study by gu et al., all patients had map after cpr in both intervention and control groups, but the amount of map in the intervention group was not different from the control group (23), which are inconsistent with the findings of the present study. to justify this finding, it can be argued that applying abdominal pressure in the intervention group increased blood circulation and blood pressure, and as a result, the amount of map in the intervention group decreased less than the control group. in terms of spo2 rate, there was no significant difference between the two groups immediately (p = 0.887) and also half an hour after (p = 0.292) the start of resuscitation, but the rate of change between these two times in the two groups was statistically significant and the control group had a higher increase in spo2 than the intervention group. in zhang et al.’s study, it was found that the level of spo2 after std-cpr increased more than iac-cpr (11), which is in line with the results of the present study. in terms of pao2 levels, there was no significant difference between the two groups immediately after the start of cpr, but there was a significant difference at half an hour after the start of cpr. the changes of pao2 in the control group from immediately to half an hour after cpr was not significant, but in the intervention group it had significantly increased (p <0.001). in the study by zhang et al. it was found that pao2 levels increased half an hour after iac-cpr (from 45.15 to 60.68), but no change was reported in the std-cpr method and the change in the intervention group was significant (11), which is consistent with the findings of the present study. in justifying this finding, it can be argued that by applying abdominal pressure in the intervention group, the rate of general and pulmonary circulation increased and, therefore, it caused a greater increase in arterial blood oxygen pressure in the intervention group compared to the control group. in terms of arterial blood ph immediately after cpr, there was no significant difference between the two groups (p = 0.102), but the difference was significant half an hour after the start of cpr (p <0.001) and both groups had a significant decrease and the rate of decrease was greater in the intervention group. according to the study by zhang et al., the ph level in both intervention and control groups had decreased after cpr and this decrease was more in the intervention group (p = 0.037). also, in this study, the intervention group’s ph (7.06) was lower than the control group (11); the findings of the current study are in line with their findings. to justify this finding, it can be argued that applying abdominal pressure in the resting phase of chest massage improves perfusion and blood flow to the heart muscle and increases cardiac output; therefore, by increasing cardiac output and blood flow to tissues, the amount of arterial blood co2 decreased, so the decrease in paco2 was compensated by the decrease in serum bicarbonate, as a result, arterial blood ph in the intervention group decreased more than the control group. in terms of paco2, it was found that there was no significant difference between the two groups immediately (p = 0.106) and half an hour (p = 0.932) after the start of cpr. in the control group, the change in paco2 from immediately to half an hour after the start of cpr was not statistically significant (p = 0.199), but in the intervention group it was significant and more than the control group (p <0.001). according to the study by zhang et al., the rate of paco2 had significantly reduced in the intervention group after cpr, while this parameter had not changed in the control group (p = 0.009) (11), which is in line with the findings of the current study. finally, all of the 8 patients who had survived after iaccpr had been discharged from hospital, but in the std-cpr group, only 5 out of the 8 patients had been discharged from hospital. 5. strength and limitations so far, very few studies in this field have been done in iran and doing this study was one of our strengths. also, our study had some limitations. firstly, since this study has been conducted on a limited number of samples, in order to generalize this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. ghanbari khanghah et al. 8 its results, it is necessary to conduct more studies in various centers and on a larger number of patients with cardiopulmonary arrest. secondly, no neurological assessment of survived patients had been done. 6. conclusion the findings of the current study show that iac-cpr has had a positive effect on cpr-related outcomes. so in this regard, it is recommended to conduct more extensive research and on a larger sample size to increase the generalizability of the present findings and include this technique in cpr guidelines in the future. 7. declarations 7.1. acknowledgments this study is a part of a msc dissertation in emergency nursing and all authors are very thankful to nurses, physicians, patients, and all those who helped us in this research. 7.2. authors’ 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resuscitation and resuscitation outcome during asystole and electromechanical dissociation. circulation. 1992;86(6):1692-1700. 22. mateer jr, stueven ha, thompson bm, aprahamian c, darin jc. pre-hospital iac-cpr versus standard cpr: paramedic resuscitation of cardiac arrests. am j emerg med. 1985;3(2):143-146. 23. gu c, liu s, liu k, xie y, wang l. effects of interposed abdominal pulling-pressing cardiopulmonary resuscitation on hemodynamics and oxygen metabolism in patients with cardiac arrest. zhonghua wei zhong bing ji jiu yi xue. 2019;31(11):1406-1410. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strength and limitations conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e47 or i g i n a l re s e a rc h basic life support (bls) knowledge among general population; a multinational study in nine arab countries nour shaheen1, ahmed shaheen1, rehab adel diab2,9∗, abdelrahman mohmmed1, abdelraouf ramadan3, sarya swed4, muhannad wael5, mrinmoy kundu6, sama soliman7, mohamed elmasry1, sheikh shoib8,10,11,12 1. alexandria university, alexandria faculty of medicine, alexandria, egypt. 2. al-azhar university, al-azhar faculty of medicine, cairo, egypt. 3. helwan university, faculty of medicine, cairo, egypt. 4. faculty of medicine, aleppo university, aleppo, syria. 5. an najah national university, faculty of medicine, nablus, palestine. 6. institute of medical sciences & sum hospital, bhubaneswar, india. 7. the pavlov first state medical university of st. petersburg, faculty of medicine, st. petersburg, russia. 8. department of psychiatry, jawahar lal nehru memorial hospital, srinagar, jammu & kashmir, india. 9. medical research group of egypt, cairo, egypt. 10.department of health services, srinagar, 190001 india. 11.sharda university, greater noida, india (ssh). 12.psychosis research centre, university of social welfare and rehabilitation sciences, tehran, iran. received: may 2023; accepted: june 2023; published online: 11 july 2023 abstract: introduction: basic life support (bls) is a medical treatment used in life-threatening emergencies until the sufferer can be properly cared for by a team of paramedics or in a hospital. this study aimed to assess the level of knowledge regarding bls and the contributing factors among the arab non-medical population. methods: an online survey-based cross-sectional study was conducted among non-medical populations in nine arab countries between april 13, 2022, and june 30, 2022. the utilized questionnaire consisted of two parts: part one included socio-demographic characteristics and part two measured knowledge of bls through an online survey. results: the research included a total of 4465 participants. 2540 (56.89%) of the participants were knowledgeable about bls. the mean basic life support knowledge scores of participants who received training were higher than those who had not (20.11 ± 4.20 vs. 16.96 ± 5.27; p< 0.01). according to the nations, yemen scored the highest, while morocco had the lowest levels of bls knowledge (19.86 ± 4.71 vs. 14.15 ± 5.10, respectively; p< 0.01). additionally, individuals who resided in urban areas scored on average higher than those who did in rural areas (17.86 ± 5.19 vs. 17.13 ± 5.24, p= 0.032) in understanding basic life support. age, information sources, and previous training with theoretical and practical classes were significant predictors of bls knowledge. conclusion: the level of bls knowledge among non-medical people in arab nations is moderate but insufficient to handle the urgent crises that we face everywhere. in addition to physicians being required to learn the bls principles, non-medical people should also be knowledgeable of the necessary actions to take in emergency events. keywords: awareness; basic life support; cardiopulmonary resuscitation cite this article as: shaheen n, shaheen a, adel diab r, mohmmed a, ramadan a, et al. basic life support (bls) knowledge among general population; a multinational study in nine arab countries. arch acad emerg med. 2023; 11(1): e47. https://doi.org/10.22037/aaem.v11i1.1975. ∗corresponding author: rehab diab; al-azhar university, al-azhar faculty of medicine, cairo, egypt. tel: +20 127 245 1274postal code: 44718, email: radledeab@gmail.com; rehab_diab97research@outlook.com, orcid: https://orcid.org/0000-0002-6552-4900. 1. introduction basic life support (bls) is the first line of management for an illness or injury, generally by any bystander, until medical intervention can be started (1). patients’ survival probability depends on early detection of symptoms, early access to emergency medical services, and early bls provided this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 2 by bystanders. additionally, studies have shown that bls can reduce recurrence and complications of the disease (2). bls standard includes recognition of sudden cardiac arrest (sca), heart attacks, strokes, and foreign body airway obstructions, as well as the use of automated external defibrillators for cardiopulmonary resuscitation (cpr) and defibrillation (3). certain illnesses or minor injuries can be treated with appropriate bls without requiring medical consultation or risk of life loss (4). so, bls knowledge should be adequate for individuals to deliver lifesaving measures in emergencies (5,6). in different communities, sudden cardiac arrest, the leading cause of death worldwide, is associated with varying survival rates (7,8). early recognition of cardiac arrest and initiating cpr reduce morbidity and mortality (7,9,10) in a previous study conducted in arizona, bystander cpr rates increased from 28.2% to 39.9%, and out-of-hospital cardiac arrest (ohca) survival rates increased from 3.7% to 9.8% following a statewide hands-only cpr campaign (11). in the united states, there are approximately 300,000 cases of ohca, with a 92% mortality rate (11). bls is performed by the first person to intervene, and using an aed doubles the chances of survival (11). there are several reasons bystanders have difficulty performing cpr: inadequate knowledge or training, a lack of skill or confidence, and a fear of legal action (11). in a study conducted in saudi arabia, which included 301 participants, only 39.2% passed the test that valued the theoretical knowledge of bls even though the percentage of participants with bachelor’s degrees exceeded 60% (12). researchers conducted an observational study with 121 participants, including dental personnel, house officers, and nurses, and found that the average health care worker lacked adequate cpr and bls knowledge (13). the same results were found in another study conducted at a medical school in oman. of 304 medical students, 53.6% had insufficient knowledge, and 64.5% had no previous bls training. however, the study stated that the students showed positive attitudes toward bls training and were not hesitant to provide bls to a stranger if needed (14). the community requires adequate training on bls, either in person or online, to provide proper care (15). increasing public awareness and understanding of how bls works is essential for a successful outcome following an emergency. the knowledge and perception of bls among the arab community have not been assessed. in general, non-medical individuals do not receive formal training in bls, leading to lack of knowledge. this study aimed to assess the level of knowledge regarding bls and the contributing factors among the arab non-medical population. 2. methods 2.1. study design and setting an online survey-based cross-sectional study was conducted among the non-medical population in most arab countries across social media ( jordan, iraq, egypt, palestine, bahrain, yemen, syria, sudan, algeria, and morocco) using an internet-based approach to communication (social media) such as facebook and twitter from april 13, 2022, to june 30, 2022, to assess their knowledge about bls. two national collaborators distributed the survey, and a secure platform was used (microsoft forms forms). only the lead investigator had access to the data; all responses were anonymous and devoid of identifying information. institutional review board (irb) approval was also obtained from the research ethics clearance committee of gadarif teaching hospital. consents were obtained from all participants before starting to fill out the online survey on the first page. all participating universities were provided with a report of data results and their interpretation, which may be used for educational program development. furthermore, the study was performed adhering to the ethical principles introduced in the declaration of helsinki. 2.2. participants the sample population was chosen through a convenience sampling method. only arab individuals over 18 who lived in the included countries and were not members of the medical field were included in our study; however, we excluded individuals under the age of 18 who did not reside in the included countries and members of the medical sector. after removing the duplicate entries, only fully completed replies were considered. 2.3. data gathering the study questionnaire was adopted from a similar study conducted in gondar town (16). the questionnaire was translated into arabic by a translator with a master’s degree. after three experts evaluated the arabic and original versions, the translation was finalized. cardiology professionals evaluated the questionnaire’s clarity and validity, followed by a pilot study with a 10% sample size (approximately 300 participants). the whole data set did not include the pilot study’s sample data. as determined by cronbach’s alpha, internal consistency was 0.841 (0.8 to 0.9: good reliability). participants could go back and change their answers. the questionnaire (supplementary file 1) was divided into two sections: a socio-demographic section: consisted of questions about personal information, including age, gender, nationality, education, marital status, residence, job status, and whether the participant had previously received bls training. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e47 knowledge of bls: this section comprised general questions related to bls definition and its principles including, the adequate time and person for performing it, knowledge of and recognizing the signs of cardiac arrest, such as being unconscious, absence of breathing, and absence of circulation, as well as the essential components of basic life support such as moving patients from accident site, stopping bleeding, applying splinting for fractures, contacting emergency medical service, and transporting patients to hospitals, and the signs of airway problems, including noisy breathing, fast breathing, slow breathing, and no breathing, and the procedures to open airway or giving breath, including jaw thrust, head tilt and chin left, mouth to mouth, mouth to nose, and the signs of bleeding, including bleeding from the injured site, victim collapsing, weak and fast pulse, and increase in respiratory rate, and preventive measures to stop the bleeding including, applying tourniquet, applying pressure and dress, and lift the injured part above the body level, and finally, the preventive measures that should be performed during transporting the patient from the accident site to the hospital. the right answer was coded as "1," whereas the wrong answer or “i don’t know” answer was coded as "0." following the addition of the right responses, individuals with scores above the mean were classified as having adequate knowledge of basic life support. in contrast, those with scores below the mean were categorized as having poor knowledge of basic life support. 2.4. statistical analysis a single population proportion formula [n = [(za/2)2. p (1p)]/d2] was used to estimate the minimum sample size. p = percentage of non-medical people in gondar town, ethiopia, who were knowledgeable about basic life support (44.4%) (16), assuming a 95% confidence level (z a/2 = 1.96), a margin of error of 5%, and a 5% addition for non-response rate. the recommended sample size was 380 individuals. participants were urged to fill out the online survey on microsoft forms, which received 4499 responses in total. after 34 participants indicated that they would not answer the questionnaire, the final sample size was 4465. after data collection, we used excel to check the data and convert the string into codes. then we exported the excel sheet to spss version 28. we ran a descriptive analysis to describe the frequency and percentages, and check if the data were normally distributed. statistical tests such as the shapiro-wilk test were used to test normality. analysis of variance (anova) was performed to investigate the difference in bls knowledge between groups defined by the independent variables. we used to compare the means between the dependent and independent variables to calculate the mean and standard deviation. finally, we used a stepwise multiple linear regression to define the best predictors of bls knowledge and the variables used were age, gender, residence (rural vs urban), education, marital status, nationality, information source, whether respondent faced an emergency, whether received training or not, type of training and number of sessions of training. a p-value below 0.05 was considered a statistically significant value. missing data is a common problem when conducting cross-sectional studies. therefore, we used complete case analysis method where we excluded participants with missing data from analysis. but to avoid bias that may occur if the missing data were not missed completely random, we conducted sensitivity analysis to evaluate the potential impact of missing data on our study results to avoid bias as much as possible and increase the validity of our finding. in order to minimize the impact of different bias to the results we took the following measures: firstly, we used a representative sampling method to select participants from a diverse range of socioeconomic backgrounds and geographic locations. this helped to reduce selection bias by ensuring that the study population was as representative as possible of the target population. second, we used standardized measurement tools and data collection procedures to ensure that all participants were evaluated in a consistent and uniform manner. this helped to reduce measurement bias and ensure that the results were comparable across participants. third, we carefully considered and controlled for potential confounding variables that may have influenced the relationship between the exposure and outcome variables. for example, we controlled for age, gender, education level, and other relevant demographic factors that may have impacted our results. finally, we conducted a sensitivity analysis to evaluate the potential impact of any unmeasured or residual confounding variables that may have influenced our results. 3. results 3.1. socio-demographic characteristics of participants among a total of 4465 study participants, the most frequent age group was 12-24 years (n= 2143 (48.0%)), while the least frequent age group was >65 years (n= 65 (1.5%)). study included 2657(59.5%) females, 3561(79.8%) urban residents, and 2867 (64.2%) single participants. a large proportion of study participants (3404 (76.2%)) did not take any training regarding bls. among participants, 2110 (47.3%) had heard about bls. furthermore, 1113 (29.2%) participants faced a case that required bls. the study included more than nine arab countries, with the largest proportion of respondents coming from jordan, 850 (19.0%) (table 1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 4 3.2. knowledge of basic life support (bls) among 4465 participants who took part in the study, 2540 (56.89%) were knowledgeable about bls. trained participants possessed higher bls knowledge scores than those who had not been trained (20.11 ± 4.20 vs. 16.96 ± 5.27; p =0.01). moreover, participants who resided in urban areas had a significantly higher mean score of bls knowledge than those from rural areas (17.86 ± 5.19 vs. 17.13 ± 5.24; p= 0.03). yemeni participants scored the highest mean score on bls knowledge, while morocco scored the least (19.86 ± 4.71 vs.14.15 ± 5.10; p <0.01). health-sector employees scored the highest mean of bls knowledge (20.27 ± 4.28). also, previous bls training sessions affected their score greatly to be significantly higher than those who did not get any previous training (20.11 ± 4.20 vs16.96 ± 5.27p= 0.02; table 2 and figure 1). furthermore, the individuals that are knowledgeable about the bls were mostly yemeni (19%) and jordanian (17%) participants (figure 2). 3.3. factors associated with knowledge of participants about bls a stepwise multiple linear regression analysis was performed to build a significant model with a p-value <0 .001 and an rsquared value of 0.91, which means the model can explain 91% of the variance in the bls knowledge score. no violations of linearity were detected. age, information sources, and previous training with theoretical and practical classes were significant predictors of bls knowledge. receiving information about bls from reading sources and health professionals was associated with better bls knowledge scores than other information sources. additionally, age groups 45-54 and 55-64 are better predictors of a higher bls knowledge score than other age groups (table 3). 4. discussion the present study aimed to evaluate the knowledge of bls among the general public in several arab countries. a total of 4465 participants were included in the study, representing a diverse range of socio-demographic characteristics. results of the study revealed that 56.89% of the participants had adequate knowledge about bls, with prior training and age being the most significant factors impacting the degree of knowledge. the study found that a large proportion of participants (76.2%) did not receive any training regarding bls, and only 47.3% of participants had previously heard about bls. additionally, only 30.1% of participants had faced a case that required bls. these findings suggest that there is a significant gap in the knowledge and understanding of bls among the general public in the arab countries included in the study. the results also revealed that urban dwellers and those who had previously received bls training had higher mean scores than those who did not. furthermore, being an employed male participant and residing in age groups (45-54) and (5564) were the factors contributing most to bls knowledge. older male participants and those who had more exposure to such situations had higher knowledge scores in bls. in terms of country-specific results, participants from yemen scored the highest mean score on bls knowledge, while participants from morocco scored the lowest. this suggests that there may be significant variation in the knowledge and understanding of bls among different arab countries, highlighting the need for targeted interventions to improve bls knowledge in specific countries. the study also found that receiving information about bls from reading sources and health professionals was associated with better bls knowledge scores than other information sources. this highlights the importance of providing accurate and accessible information about bls to the general public through various media sources. training raises awareness, which contributes to raising the degree of knowledge compared to individuals who never get training, as documented in previous research, and this may be confirmed by the fact that trained personnel performed better than untrained personnel in the study (12,15,17-20). a crucial argument is that, despite certain participants’ expertise and experience, it is unfair for them to get involved in the situation or administer cpr unless they have a legal obligation to do so (20). study results showed that older participants who aged more than 45 years had higher knowledge scores than younger participants. this finding is consistent with the findings of the saudi arabia research, which revealed that older participants had greater knowledge scores than younger participants, even though the majority of the samples gathered are from younger age groups. older persons have been exposed to more cases that need bls as they have aged (18). in this research, male participants had greater knowledge scores than females. even though there were more women than men in the population. the findings of this research may be attributed to the cultural and societal factors present in the middle eastern nations where the study was conducted. specifically, the conservative nature of these societies may have led to a higher level of knowledge and exposure to relevant scenarios among males, as compared to females. this is supported by the findings of a previous study conducted in portugal, which also highlighted the role of work environments in providing opportunities for exposure and the exchange of information related to these situations among males (21). the present study found that knowledge of basic life support (bls) is greater among urban inhabitants as compared to rural ones. this difference may be attributed to the fact that urthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e47 ban populations tend to have higher levels of education and better access to educational resources, including bls training programs. conversely, rural populations may have limited access to educational resources, and poor educational abilities, which can impede their ability to learn from various sources such as reading. furthermore, urban communities have greater access to shareable information, including media sources, which may have contributed to their increased knowledge of bls. additionally, the study found that individuals who were employed performed better on the bls knowledge test than those who were unemployed. this is likely due to the fact that those working earn greater wages, which allow them to afford to attend bls courses and receive training. however, the high tuition for these courses may prevent unemployed individuals from enrolling, highlighting the need for governmentfunded initiatives to provide bls training to fill the gap created by discrepancies in wages and educational levels (22). the study also found that participants in the healthcare industry performed better than those in other occupations, which may be due to the nature of their work and its impact on their knowledge of bls. furthermore, the study found that having access to the media and the internet may be a key factor in determining the response rate, which could explain why the response rate was greater in jordan and lower in iraq. however, yemen had the highest mean score, with only 8% of participants coming from yemen classified as having poor knowledge of bls. conversely, participants from egypt, jordan, and syria comprised 51% of this total. additionally, yemen had a higher mean score than any other nation because it is a war-torn nation with a greater need for basic life support than other nations (23). this study showed a higher percentage of the population who had knowledge regarding the bls compared to some studies conducted on non-medical staff such as those performed in addis ababa (17) among kindergarten teachers, iran (24) within a school environment, and saudi arabia over the general population (18), which reported 40.0%, 45.8%, 40.3% knowledgeable population, respectively; closer to percentages reported in other studies conducted in addis ababa (25) among medical and non-medical students and saudi arabia among rural mothers (26), which reported 50.3% and 50.0% knowledgeable population, respectively; in line with results reported in a study conducted in china among elderly population (27) with 57.3%; and lower than the percentage reported in egypt among rural mothers (19) with 74.3% of participants showing a considerable knowledge regarding bls. the variations are caused by different tools and cut-off points. variations in the educational backgrounds of included individuals also play an essential role in their awareness. 5. recommendations based on the findings of the present study, recommendations for improving bls knowledge and understanding among the general public in arab countries include: • providing affordable and accessible bls training courses to the general public • raising public awareness of the importance of bls through various media sources • targeted interventions to improve bls knowledge in specific countries with lower scores • encouraging health professionals to provide information and education on bls to the general public • promoting policies and initiatives that make it easier for people to access bls training. the present study highlights the need for targeted interventions to improve the knowledge and understanding of bls among the general public in arab countries. by making bls training more accessible and affordable, raising public awareness of the importance of bls, and providing accurate and accessible information about bls through various media sources, it is possible to improve bls knowledge and understanding among the general public, ultimately leading to better outcomes in emergency situations. 6. limitations the present study has several limitations that should be acknowledged. firstly, the study was conducted solely in arab countries and may not be generalizable to other populations or regions. additionally, the study relied on self-reported data, which may introduce bias and inaccuracies in the results. furthermore, the study did not assess the practical skills and abilities of the participants in performing bls, only their knowledge and understanding of the subject. it would be important to conduct further research to evaluate the practical skills and abilities of the general public in performing bls. additionally, the study only measured the knowledge and understanding of bls among the general public and did not assess the knowledge and understanding of bls among healthcare professionals. future research could also focus on evaluating the knowledge and understanding of bls among healthcare professionals in arab countries. finally, the study relied on online surveys, which may not have reached individuals without internet access or those who were not comfortable taking online surveys. this could have resulted in a selection bias and may have affected the representativeness of the sample. 7. conclusion results showed that 56.89% of participants had adequate knowledge about bls, and that factors such as previous this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 6 training and age were associated with higher bls knowledge scores. the study also found that urban residents and those who had received bls training had higher mean scores than those who had not. additionally, being an employed male participant and belonging to the age groups of 45-54 and 55-64 were found to be factors that contributed most to bls knowledge. the study highlights the need for measures such as making bls courses more accessible and affordable, and raising public awareness about the importance of bls through various media sources in order to increase the number of people with adequate knowledge about bls. overall, the study suggests that while the level of bls knowledge among non-medical individuals in arab countries is moderate, it is still insufficient to handle emergency situations, and there is a need for further education and training to ensure that individuals are prepared to respond in emergency situations. 8. declarations 8.1. acknowledgments we would like to express our gratitude to the data collection group for their valuable contribution to this project. their efforts in collecting and organizing the necessary data have been instrumental in the success of our research. we greatly appreciate their assistance and dedication throughout the data collection process. 8.2. conflict of interest the authors declare that they have no competing interests. 8.3. funding and support none. 8.4. authors’ contribution nour shaheen: conceptualization, methodology, formal analysis, writing-original draft, review, and editing. ahmed shaheen, rehab adel diab, abdelrahman mohmmed, abdelraouf ramadan, sarya swed, muhannad wael, mrinmoy kundu, sama soliman, mohamed elmasry, sheikh shoib: writing-review and editing. all authors read and approved the final manuscript. 8.5. data availability the data supporting this study’s findings are available from the first author, [nour shaheen], upon reasonable request. 8.6. ethical approval the study was performed in accordance with the ethical standards as 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gomes jcr. knowledge of the portuguese population on basic life support and availability to attend training. rev esc enferm usp. 2015;49(4):636–44. 22. gad s. health awareness campaigns on the egyptian ministry of health pages on social media. the egyptian journal of media research. 2021 oct 1;2021(77):1059–113. 23. gulland a. msf calls for urgent help for war torn yemen. bmj. . 2015 aug 11;351:h4366. 24. adib-hajbaghery m, kamrava z. iranian teachers’ knowledge about first aid in the school environment. chin j traumatol. 2019;22(4):240. 25. alsayali rm, althubaiti aqa, altowairqi rm. awareness, knowledge, attitude and practices of first aid skills among medical and non-medical students at taif university. wfm/ mejfm. 2019 ;17(11):34–43. 26. eldesouky r. home-related injuries among children: knowledge, attitudes and practice about first aid among rural mothers. east mediterr health j. 2012 oct;18(10):1021-7. 27. sun w, liu y, yan g, meng w, dong f. research on present situation of pre-hospital first-aid knowledge of the elderly in community in jilin. bio web of conferences. 2017;8:01010. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 8 table 1: socio-demographic characteristics of the studied samples (n=4465) variables values variables values age (years) nationality 12-24 2143 (48.0) jordanian 850 (19.0) 25-34 1213 (27.43) egyptian 553 (12.4) 35-44 570 (12.8) palestinian 473 (10.6) 45-54 344 (7.7) bahraini 420 (9.4) 55-64 130 (2.9) yemeni 633 (14.2) above 65 65 (1.5) syrian 488 (10.9) gender algerian 401 (9.0) male 1765 (39.5) sudani 490 (11.0) female 2657 (59.5) moroccan 60 (1.3) residency other 97 (2.2) urban 3561 (79.8) job status rural 904 (20.2) unemployed 511 (11.4) education entrepreneur/freelancer 992 (22.2) phd 9 (0.2) employed 1338 (30.0) masters 52 (1.2) health-sector employee 631 (14.1) university degree 3759 (84.2) student 898 (20.1) professional diploma 31 (0.7) retired 75 (1.7) high school 5 (0.1) bls training secondary education 582 (13.0) yes 1061 (23.8) primary education 17 (0.4) no 3404 (76.2) other 10 (0.2) ever heard about bls marital status yes 2110 (47.3) married 1514 (33.9) no 2355 (52.7) single 2867 (64.2) facing a person in need of bls widowed 84 (1.9) yes 1344 (30.1) data are presented as frequency (%). phd: doctorate of philosophy; bls: basic life support. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e47 figure 1: point-plots of association between age groups and score in the study taking into account whether the participant received training in (a) and faced an emergency requiring bls or not (b). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 10 figure 2: countries of people who had sufficient knowledge of basic life support among studied arab countries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e47 supplementary table 1: english version of the questionnaire part one: socio-demographic and general information q1. age ————— q 2. gender 1. male 2. female q3. residence? 1. urban 2. rural q4. educational status 1. no formal education 2. formal education q 5. marital status? 1. married 2. single 3. widowed 4. divorced q6. religious? 1. muslim 2. christian 3. jewish 5. others q 7. did you take basic life support training before? 1. yes 2. no q8. type of training? 1. theoretical training 2. practical training 3. both q9. the number of training sessions before? 1. one 2. two 3. three or more q10. if your answer to question no 9 ’is yes, ’where were you trained? q11. did you hear about basic life support? 1. yes 2. no q12. if yes, for q-11 source of information? 1. reading materials 2. media 3. health professionals 4. friends and relatives q13. did you get an emergency case that needs basic life support? 1. yes 2.no part two: knowledge questions q1. when should basic life support be given during an accident? 1. immediately 2. in hospital. 3. i don’t know q2. who should give basic life support during an accident? 1. health care worker 2. community policy 3. scene bystanders including community. 4. i don’t know q3. is being unconscious a sign of cardiac arrest? 1. yes 2. no 3. i don’t know q4. if you answered yes for q-3, how can you have recognized unconsciousness? 1. no reaction to voice 2. no reaction to touch 3. no movements 4. don’t know q5. is the absence of breathing a sign of cardiac arrest? 1. yes 2. no q6. if you yes for q-5, how can you recognize the absence of breathing? 1. no breathing moves 2. no breathing sound 3. no expired air 4. mirror in front of victim’s mouth 5. don’t know q7. is the absence of circulation a sign of cardiac arrest? 1. yes 2. no q8. if yes for q-7, how can you recognize absence of circulation? 1. palpation of neck arteries 2. palpation of arm arteries 3. i don’t know q9. moving patients from accident sites is a component of basic life support 1. yes 2. no 3. i don’t know q10. stopping bleeding is a component of basic life support. 1. yes 2. no 3. i don’t know q11. applying to splint for fractures is a component of basic life support 1. yes 2. no 3. i don’t know q12. communicate to emergency medical service -939 is a component of basic life 1. yes 2. no 3. i don’t know q13. transporting patients to hospitals is a component of basic life support 1. yes 2. no 3. i don’t know q14. noisy breathing is a sign of airway problem for the victim 1. yes 2. no 3. i don’t know q15. fast breathing is a sign of an airway problem for the victim 1. yes 2. no 3. i don’t know q16. slow breathing is a sign of airway problem for the victim 1. yes 2. no 3. i don’t know q17. no breathing is a sign of an airway problem for the victim 1. yes 2. no 3. i don’t know q18. jaw thrust is a procedure used to open the airway of victims 1. yes 2. no 3. i don’t know q19. head tilt and chin left is a procedure used to open the airway for accident victims 1. yes 2. no 3. i don’t know q20. mouth to mouth is used for giving breath 1. yes 2. no 3. i don’t know q21. the mouth to the nose is used for giving breath 1. yes 2. no 3. i don’t know q22. keep the person’s neck and back straight with your hand while shifting a patient to the hospital, a thing you should always assume if the cervical injury is present 1. yes 2. no 3. i don’t know q23. keep the person’s neck and back straight with a hardboard while shifting a patient to the hospital, a thing you should always assume if the cervical injury is present 1. yes 2. no 3. i don’t know q24. if there is only a limb injury, the patient is transferred in a sitting position while shifting a patient to the hospital, a thing you should always assume if the cervical injury is present 1. yes 2. no 3. i don’t know q25.bleeding from the injured site is a sign of hemorrhage 1. yes 2. no 3. i don’t know q26.victim becoming collapse is the sign of bleeding from the injured site 1. yes 2. no 3. i don’t know q27.weak and fast pulse and increased respiratory rate is the sign of bleeding from the injured site 1. yes 2. no 3. i don’t know q28.applying tourniquet is important to stop bleeding 1. yes 2. no 3. i don’t know q29. applying pressure and pressing are important to stop bleeding 1. yes 2. no 3. i don’t know q30. lifting the injured part above the body level is important to stop bleeding. 1. yes 2. no 3. i don’t know this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index n. shaheen et al. 12 table 2: the mean knowledge score of participants regarding basic life support (bls) based on different socio-demographic variables (n=4465) variables values p-value age (years) 18-24 17.38 ± 5.22 25-34 18.25 ± 5.30 35-44 17.53 ± 5.23 <0.001 45-54 18.03 ± 4.86 55-64 18.42 ± 4.70 ≥65 17.25 ± 4.58 gender female 17.54 ± 5.06 male 17.97 ± 5.35 <0.026 rather not say 17.63 ± 7.48 residency urban 17.86 ± 5.19 <0.001 rural 17.13 ± 5.24 education university degree 17.77 ± 5.20 secondary education 17.22 ± 5.08 master 17.96 ± 5.17 <0.222 professional diploma 17.32 ± 7.11 primary education 19.29 ± 6.36 other 18.20 ± 3.74 phd 19.56 ± 5.21 high school 19.60 ± 3.20 marital status single 17.62 ± 5.22 married 17.89 ± 5.19 <0.272 widowed 17.65 ± 4.77 country jordan 17.12 ± 4.92 yemen 19.86 ± 4.71 egypt 16.32 ± 5.55 sudan 18.60 ± 4.90 <0.001 syria 16.79 ± 5.00 palestine 17.33 ± 5.36 bahrain 18.74 ± 5.53 algeria 17.68 ± 4.52 other 16.82 ± 5.45 morocco 14.15 ± 5.10 job status employed 17.42 ± 5.31 entrepreneur/freelancer 17.32 ± 5.34 student 17.26 ± 5.21 health-sector employee 20.27 ± 4.28 <0.001 unemployed 16.88 ± 5.02 retired 17.48 ± 4.13 other 18.32 ± 2.15 bls training no 16.96 ± 5.27 <0.001 yes 20.11 ± 4.20 training type both 20.57 ± 3.95 theoretical training 19.07 ± 4.49 <0.001 practical training 19.36 ± 4.63 sessions of training three or more 20.68 ± 4.13 one 19.77 ± 4.30 two 19.70 ± 4.04 table 2: the mean knowledge score of participants regarding basic life support (bls) based on different socio-demographic variables (n=4465) variables values p-value heard about bls before no 16.25 ± 5.41 <0.001 yes 19.35 ± 4.43 bls information source health professionals 20.12 ± 3.91 media 18.18 ± 4.99 <0.001 reading materials 20.09 ± 4.10 friends and relatives 18.46 ± 4.35 facing a person in need of bls no 17.19 ± 5.32 <0.001 yes 18.92 ± 4.71 data are presented as mean ± standard deviation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e47 table 3: linear logistic regression analysis of the independent predictive factors regarding knowledge of basic life support among the studied participants variables coefficient 95 % ci p value lower upper information source friends and relatives 2.0545 1.407 2.702 <0.001 health professionals 2.6418 2.148 3.136 <0.001 age (year) 18-24 16.1967 15.946 16.447 <0.001 25-34 16.6735 16.342 17.005 <0.001 35-44 16.4983 16.051 16.945 <0.001 45-54 17.0346 16.463 17.606 <0.001 55-64 17.2053 16.282 18.129 <0.001 reading materials 3.3382 2.817 3.860 <0.001 training mode 1.9145 1.419 2.410 <0.001 data are presented with 95% confidence interval (ci). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion recommendations limitations conclusion declarations references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 125 emergency (2015); 3 (3): 125-126 photo quiz an 88-year-old man with sudden onset abdominal pain mohammad manouchehrifar, soheil soltani*, sona ziaei department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: soheil soltani; department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. tel: +989122196632; email: soheil_soltani@yahoo.com received: february 2015; accepted: march 2015 figure 1: us imaging of patient’s liver. figure 2: axial abdominal ct scan of patients. us: ultrasonography; ct: computed tomography cite this article as: manouchehrifar m, soltani s, ziaei s. an 88-year-old man with sudden onset abdominal pain. emergency. 2015;3(3): 125-6. case presentation: n 88-year-old man presented to the emergency department with sudden onset of abdominal pain since 6 hours before. he described his pain as an epigastric pain that had become generalized without any radiation. the pain was persistent and aggravated by meal. it was associated with nausea but not with vomiting, diarrhea, hematochezia, hematemesis or dysuria. he was a known case of chronic renal failure that underwent hemodialysis three times a week. he also suffered from hypertension and benign prostatic hyperplasia. the patient was under treatment with aspirin, atorvastatin, furosemide, finasteride, and tamsulosin. he did not use cigarette, opium or alcohol. the patients’ on-arrival vital signs were as follows: systolic blood pressure: 100/60 mmhg, pulse rate: 88/minute, respiratory rate: 25/minute, oral temperature: 36◦c, oxygen saturation 93% in room air. he had severely ill appearance on admission. lungs and heart auscultation was normal. distended abdomen was considerable but had normal bowel sound and clearly, pain was disproportionate to physical examination. rectal examination was unremarkable. pitting edema was observable on his lower limbs; however, symmetric peripheral pulses were detected. his electrocardiogram showed sinus rhythm and venous blood gas analysis revealed the following: ph=6.96, paco2=49 mmhg, hco3=11 meq/l, base excess= 20. by reviewing the biochemistry profile only urea=180 mg/dl and creatinine=4.8 mg/dl were notable and all others such as amylase, lipase, and liver function tests were reported in normal range. the bedside ultrasonography showed echogenic particles in hepatic parenchyma and same findings that were passing through the portal vein (figure 1). chest and abdominal x-rays were reported as normal. the patient underwent abdominal and pelvic computed tomography (ct) scan with oral contrast that showed in figure 2. what is your diagnosis? a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 126 manouchehrifar et al diagnosis: air in portal vein and its branches combined with air in intestinal wall that all are consistent with diagnosis of mesenteric ischemia and pneumatosis intestinalis. case fate: the patient admitted to the intensive care unit because of severe acidosis and worsening hemodynamic, but died after 3 days. discussion: abdominal pain is among the most frequent problems of patients referred to emergency department (1). hepatic portal venous gas (hpvg) is a rare condition that is associated with accumulation of gas in the portal venous circulation. this condition was historically linked to high morbidity and mortality in patients with acute abdomen (2, 3). case series have shown that overall mortality rate of hpvg is between 29-39%, depending on the underlying etiology (4, 5). most fatal cases with hpvg are secondary to development of mesenteric ischemia with extended bowel necrosis. however, there are some reports that have indicated the presence of hpvg in certain non-ischemic conditions with good prognosis (4). despite the fact that finding air in the portal vein is not a diagnosis by itself, hpvg may give clinicians some hints for the diagnosis of underlying medical conditions. without using advanced radiological techniques, detecting air in the portal vein is not an easy for clinicians, since abdominal plain x ray does not detect portal air in 80% of cases (2, 6). air in the portal vein is visible as echogenic bubbles in ultrasound imaging (7). abdominal ct scan is another imaging modality, which is more sensitive and maybe used in referral centres. abdominal ct scan and ultrasonography can also be used to investigate underlying conditions in such patients. based on published manuscripts, chronic renal failure might have a role in pathogenesis of hpvg (8-10). hpvg in patients with chronic renal failure might be linked with non-occlusive mesenteric ischemia (9). chronic kidney disease is a known cause of vascular calcification and mesenteric vascular complications (11). therefore, there is controversy regarding whether chronic renal failure cases are more vulnerable to present mesenteric ischemia accompanied with hpvg or not. this relationship needs further investigation in future studies. acknowledgment: we acknowledge all staff of emergency department of loghmane hakim hospital, tehran, iran. conflict of interest: there was no conflict of interest. author’s contribution: all the authors have contributed to drafting/ revising the manuscript, study concept, or design, as well as data interpretation. references: 1. forouzanfar m, hatamabadi h, hashemi b, et al. outcome of nonspecific abdominal pain in the discharged patients from the emergency department. j gorgan uni med sci. 2014;16(2):62-8. [persian]. 2. kesarwani v, ghelani dr, reece g. hepatic portal venous gas: a case report and review of literature. indian j crit care med. 2009;13(2):99-101. 3. baratloo a, rahmati f, rouhipour a, et al. correlation of blood gas parameters with central venous pressure in patients with septic shock; a pilot study. bull emerg trauma. 2014;2(2):77-81. 4. kinoshita h, shinozaki m, tanimura h, et al. clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature. arch surg. 2001;136(12):1410-4. 5. faberman rs, mayo-smith ww. outcome of 17 patients with portal venous gas detected by ct. am j roentgenol. 1997;169(6):1535-8. 6. yip c, ng v, man d, metreweli c. sonographic recognition of pneumatosis intestinalis and portal gas in an 11‐months‐old infant—case report. australas radiol. 1990;34(2):169-71. 7. lafortune m, trinh b, burns p, et al. air in the portal vein: sonographic and doppler manifestations. radiology. 1991;180(3):667-70. 8. morimoto y, yamakawa t, tanaka y, hiranaka t, kim m. recurrent hepatic portal venous gas in a patient with hemodialysis‐dependent chronic renal failure. j hepatobiliary pancreat surg. 2001;8(3):274-8. 9. iguchi s, alchi b, safar f, et al. hepatic portal venous gas associated with nonocclusive mesenteric ischemia in a hemodialysis patient. clin nephrol. 2005;63(4):310-2. 10. chang c-j, shun h-c, chuang c-c. hepatic portal venous gas induced by emphysematous pyelonephritis: a rare case in hemodialytic women. am j emerg med. 2009;27(9):1171. e1-. e3. 11. soriano s, carmona a, triviño f, et al. endothelial damage and vascular calcification in patients with chronic kidney disease. am j physiol renal physiol. 2014;307(11):f1302-f11. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 108 emergency (2016); 4 (2): 108-110 casr report eosinophilic gastroenteritis as a rare cause of recurrent epigastric pain mohammad taghi safari, shabnam shahrokh, mohammad bagher miri, mohammad javad ehsani ardakani* gastroenterology and liver diseases research center, research institute for gastroenterology and liver diseases, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mohammad javad ehsani ardakani; research institute for gastroenterology and liver diseases, velenjak street, shahid chamran highway, tehran, iran. tel: +98 21 22 43 99 82, email: mjehsani@yahoo.com received: july 2015; accepted: august 2015 abstract eosinophilic gastroenteritis (ege) is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. it can mimic many gastrointestinal disorders due to its wide spectrum of presentations. diagnose is mostly based on excluding other disorders and a high suspicion. here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of ege. keywords: eosinophilic enteropathy; abdominal pain; endoscopy, gastrointestinal; emergency department cite this article as: safari mt, shahrokh s, miri mb, ehsani ardakani mj. eosinophilic gastroenteritis as a rare cause of recurrent epigastric pain. emergency. 2016; 4(2):108-110. introduction: osinophilic gastroenteritis (ege) is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. it can mimic many gastrointestinal disorders due to its wide spectrum of presentations (1, 2). diagnose is mostly based on excluding other disorders and a high suspicion (3). despite of its low prevalence, ege should be considered as diagnosis in case of recurrent abdominal pains. lesion biopsies are inevitable for confirming diagnosis and corticosteroids are alternative treatment for remission (4). here we report a case of 26-yearold man with a history of sever epigastric pain followed by nausea, vomiting, and oral intake intolerance with final diagnosis of ege. case report: a 26-yearold man was seen in emergency department because of severe abdominal pain since one week before admission. his pain was localized to epigastric area, had burning type and aggravated with feeding without any radiation site and was associated with nausea, vomiting and food intolerance. he had no fever, chills, night sweeting, evidence of gastrointestinal bleeding, change in bowel habit, or icterus. on examination, his vital signs were stable and cardiopulmonary examination was normal. he had severe epigastric tenderness without rebound and guarding or distention and bowel sound was present. his past habitual and medical history has been unremarkable except for allergic rhinitis since five years ago. complete blood count, serum electrolytes, renal and liver function tests, amylase, lipase, and stool exam for parasites and occult blood were all in normal range. esophagogastroscopy revealed very severe patchy congestion and erosion along with superficial ulcers in proximal of body, as well as congestion and erythema in mucosa of entire stomach. bulb and d2 was severe congestive. multiple biopsies were taken from stomach and duodenum (figure1, 2). histology revealed portion of small intestinal mucosa with intact villous and corpus architecture. there are dens infiltration of eosinophilic inflammatory cells and evidence of their degranulation in lamina properia and submucosa. after ruling out of parasite infection and malignancy and involvement of other organs with negative studies including multiple stool examinations, serology for certain parasites, evaluation of biopsies for malignant cells and other infiltrations, chest and abdominopelvic computed tomography (ct) scan, and echocardiography diagnosis of ege was established. treatment with 25 mg prednisolone was began and after 2 days significant resolution of his symptoms was seen. in follow up, after one month, he was completely well, without complain of abdominal pain and nausea or vomiting. discussion: eosinophilic gastroenteritis (ege), is a rare inflammatory disorder characterized by eosinophilic infiltration of gi tract wall, especially stomach and duodenum (1). there are limited data on epidemiology of ege. the prevalence in us is 22-28 per 100000 cases. e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 109 emergency (2016); 4 (2): 108-110 it is mostly seen in white and to some extent asians and affects adults and children of both sexes with a slight male preponderance (2, 5). patients present clinically at any age with a peak between third to fifths decades (1, 5). depending on the location, depth and extent of bowel wall involvement, ege has a broad spectrum of clinical manifestations from abdominal pain, nausea and vomiting to gastrointestinal obstruction and ascites, which can mimic most of gastrointestinal and abdominal pathologies. high serum level of ige is common in these patients. eczema, atopic diseases, such as asthma, may be accompanied. it also runs a chronic relapsing course (1, 2, 4). the diagnosis is difficult and is mostly based on excluding other diagnoses and a high clinical suspicion. the presence of abnormal gastrointestinal symptoms, along with 20 or more eosinophil per high-power field in one or more areas of the gastrointestinal tract, absence of an identified cause of eosinophilia (parasites, drug use, and malignancy), exclusion of eosinophilic involvement in organs other than the gastrointestinal tract and a history of atopy or food allergies are often necessary for diagnosis (3, 4). the macroscopic appearance of tissue is nonspecific and lesion biopsies are inevitable for confirming diagnosis (6). gastrointestinal obstruction is the most common complication. treatment should be individualized, considering patient’s age and severity of the symptoms. there are several reports on the role of elemental or elimination diet on improvement in disease activity (1-3, 5). in patients in whom, diet restriction is not feasible or has failed, low dose steroid therapy is the main therapeutic alternative. antihistamines (ketotifen), mast cell stabilizer (oral chromoglycate), and leukotriene antagonists (montelukast) are also used in its treatment (7, 8). flare-ups can also be controlled with oral corticosteroids (9). in case of gastrointestinal obstruction, surgery may be inevitable. conclusion: eosinophilic gastroenteritis is a rare cause of epigastric pain but, should be considered as differential diagnosis in cases of recurrent abdominal pain. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. ingle sb, hinge cr. eosinophilic gastroenteritis: an unusual type of gastroenteritis. world journal of gastroenterology: wjg. 2013;19(31):5061. 2. lucendo aj, arias a. eosinophilic gastroenteritis: an update. 2012. 3. prussin c. eosinophilic gastroenteritis and related eosinophilic disorders. gastroenterology clinics of north america. 2014;43(2):317-27. 4. spera m, nicaud m, gupta m, raines d, editors. a case of subserosal eosinophilic gastroenteritis presenting with figure 1: endoscopy and microscopic views of lesion. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com safari et al 110 abdominal pain and distension. journal of investigative medicine; 2014: lippincott williams & wilkins 530 walnut st, philadelphia, pa 19106-3621 usa. 5. temiz t, yaylacı s, demir mv, kahyaoglu z, tamer a, uslan mi. eosinophilic gastroenteritis: a rare case report. north american journal of medical sciences. 2012;4(8):367. 6. kinoshita y, furuta k, ishimaura n, et al. clinical characteristics of japanese patients with eosinophilic esophagitis and eosinophilic gastroenteritis. journal of gastroenterology. 2013;48(3):333-9. 7. reed c, woosley jt, dellon es. clinical characteristics, treatment outcomes, and resource utilization in children and adults with eosinophilic gastroenteritis. digestive and liver disease. 2014. 8. mori a, enweluzo c, grier d, badireddy m. eosinophilic gastroenteritis: review of a rare and treatable disease of the gastrointestinal tract. case reports in gastroenterology. 2013;7(2):293. 9. dai y-x, shi c-b, cui b-t, wang m, ji g-z, zhang f-m. fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis. world journal of gastroenterology: wjg. 2014;20(43):16368. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 54 emergency (2015); 3 (2): 54-58 original research diagnostic accuracy of optic nerve ultrasonography and ophthalmoscopy in prediction of elevated intracranial pressure keihan golshani1, mehdi ebrahim zadeh2*, ziba farajzadegan3, fariborz khorvash4 1. department of emergency medicine, alzahra hospital, isfahan university of medical sciences, isfahan, iran. 2. department of emergency medicine, nemazi hospital, shiraz university of medical sciences, shiraz, iran. 3. community medicine department, faculty of medicine, isfahan university of medical sciences, isfahan, iran. 4. isfahan neurosciences research center, isfahan university of medical sciences, isfahan, iran. *corresponding author: mehdi ebrahim zadeh; nemazi hospital, zand st, nemazi sq, shiraz, iran. tel: +989121485224; email: drme.teb90@yahoo.com received: september 2014; accepted: november 2014 abstract introduction: elevated intracranial pressure (icp) is a major and potentially lethal disorder in patients admitted to the emergency department (ed). several methods are being used to investigate for elevated icp. here we assessed and compared the diagnostic accuracy of two existing tools of ophthalmoscopy and optic nerve ultrasonography in detection of elevated icp. methods: 131 participants with probable elevation of icp referred to the emergency department of al-zahra hospital, isfahan, iran, from 2012 to 2014, were enrolled. brain computed tomography (ct) scan, ultrasonography of optic nerve sheath, and ophthalmoscopy were performed for them. the optic nerves sheath with diameter more than 5 millimeters was considered as elevated icp. widening of optic nerve, ocular venous engorgement, blurring, hemorrhage over optic disk, elevation of optic disk, and retinal venous tortuosity were recorded as evidences of icp rising in ophthalmoscopy. diagnostic accuracy of the two tools in prediction of icp rising were compared with the results of brain ct scan as a gold standard. results: the mean age of participants was 46.29 ± 10 years (77% male). the number of diagnosed elevated icps with ophthalmoscopy and ultrasound were 98 (74.8%) and 102 (77.9%) cases, respectively. the calculated sensitivity and specificity of ophthalmoscopy and ultrasonography in detection of icp rising were 100.0% (95% ci: 88.6-100.0) and 35.4% (95% ci: 26.0-46.2), 100.0% (95% ci: 84.0-100.0) and 31.9% (95% ci: 23.0-41.7), respectively. conclusion: the present study revealed that bedside ultrasonography of optic nerve sheath and ophthalmoscopy have enough accuracy for the screening of patients with probable elevation of icp. of course, it should be considered that despite the high sensitivity of both tools, their specificity is low. key words: ultrasonography; ophthalmoscopy; diagnostic tests, routine; physical examination; optic disk cite this article as: ebrahim zadeh m, golshani k, farajzadegan z, khorvash f. diagnostic accuracy of optic nerve ultrasonography and ophthalmoscopy in prediction of elevated intracranial pressure. emergency. 2015;3(2): 54-8. introduction: ncreased intracranial pressure (icp) is a major and potentially lethal disorder in patients admitted to the emergency department (ed) (1-3). a normal icp varies from zero to 15 millimeters of water (mmh2o), while in a case of head trauma it rises up to 20 mmh2o or higher, leads to severe damage to the intracranial structures (4). brain parenchyma, cerebrospinal fluid (csf), and blood circulation are three main components in the skull that may cause an increased icp if their balance is disturbed (5). however, regardless of the etiology, elevated icp usually presents common signs and symptoms. patients with increased icp are often presented by headache, nausea, vomiting, and progressive decline in their consciousness. the well-known cushing triad defined as hypertension, bradycardia, and respiratory depression is the end-stage presentation in these patients (5). more precise and reliable methods are being used to diagnose patients with elevated icp (3). to label a patient definitely with elevated icp, a direct and invasive sampling of the csf, also known as spinal tap, is required. the measured pressure is then considered as the golden standard of icp (3, 6). it has been established that not all patients are eligible for such procedure and in cases of high icp levels, as the result of space-occupying lesions, spinal tap is contra indicated; therefore, the need for more applicable icp screening methods have yet existed. ct scan is an excellent way to study intra cranial i this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 55 emergency (2015); 3 (2): 54-58 structures. several imaging findings in ct scan are indicative of elevated icp, including cerebral edema, midline structural shift, ventricular collapse, and ventricular enlargement (7). ophthalmoscopy has also been used to promptly interpretation of icp status through ocular examination (8). another way to determine whether a patient has elevated icp is using the sonographic optic nerve sheath diameter (onsd). in this method, the optic nerve sheath diameter larger than 5 millimeters is the indirect indicator of elevated icp (3, 9, 10). based on the above-mentioned, the present study aimed to evaluate the diagnostic accuracy of ophthalmoscopy and ultrasonography of optic nerve sheath in compare to brain ct scan in prediction of elevated icp. methods: in the present diagnostic trial, we consecutively enrolled 131 patients suspected to icp elevation and referred to the emergency department of alzahra hospital, isfahan, iran, from 2012 to 2014. the protocol of this study was reviewed and approved by ethic committee of isfahan university of medical sciences. the study was designed and conducted according to the helsinki declaration and after complete explanation of the procedure for patients, written informed consent was obtained from all studied participants. all included subjects were positive for signs of elevated icp in their history and examination including nausea, vomiting, altered consciousness, and a compatible chief complaint for related diagnoses such as head trauma. in addition, age less than 18, direct trauma to the eye, ophthalmic diseases, and treatment with medications affecting intracranial pressure were defined as exclusion criteria. by considering the sensitivity of 0.9 and prevalence of 30% (11), α = 0.05, and precision of 10% (d = 0.1), a minimum sample size with 117 patients was considered to be appropriate. after the patients’ hemodynamic state was stabilized in the ed, ophthalmoscopy and brain ct scans were performed and findings recorded. cerebral edema, midline structural shift, ventricular collapse, ventricular enlargement, and cistern compression were desired signs of icp rising in brain ct scan. widening of optic nerve disk, ocular venous engorgement, blurring, hemorrhage over optic nerve disk, elevation of optic disk, and retinal venous tortuosity were recorded as the signs of icp rising in ophthalmoscopy. in addition, onsd more than 5 millimeters was considered as the sonographic sign of icp elevation. all ct scans were interpreted and reported by a skilled radiologist and direct ophthalmoscopy performed by ed physicians during the bedside examinations, too. ct scans were obtained by a helical ct scan machine (siemens somatom emotion 16-slice ct system) and the images taken from the entire skull at a transverse view. for measurement of sonographic diameter of optic nerve, participants were asked to close their eyes. the ultrasonography was done by the method described by amini et al. (12). briefly, a 7.5 mega hertz probe linear transducer (hs2000, honda, korea), sized 5.5 × 1 centimeter, was placed on the center of each eye. participants were asked to keep their eyes in supine position if they were looking ahead to minimize the rotation of imaging. each optic nerve was measured three times and the mean number recorded. the mean value of two right and left optic nerve sheaths were entered in the analysis. any patient who had an optic nerve with diameter greater than 5 millimeters was considered to have elevated icp. ultrasonography was performed before awareness from the result of brain ct and the operator was blind to the patient’s clinical condition to prevent diagnostic suspicion bias. statistical analysis data were analyzed using stata version 11.2 statistical software. brain ct was defined as a gold standard. receiver operating characteristic (roc) and computing of the area under curve (auc) were used to confirm the adequacy of model and select the optimum cut off for ophthalmoscopy. with assessing five ophthalmic signs in the present study, we designed a six score model (zero = no abnormal finding; five = five abnormality) for measurement of diagnostic accuracy of ophthalmoscopy. finally, sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of ultrasonography and ophthalmoscopy in prediction of icp rising were calculated. table 1: baseline characteristics of patients variable number (%) gender male 101 (77.1) female 30 (22.9) diagnosis pseudo-tumor cerebri 26 (20.2) epilepsy 15 (11.4) cerebral vein thrombosis 13 (9.9) loss of conciseness 11 (8.4) ich and ivh 11 (8.4) subarachnoid hemorrhage 10 (7.6) hydrocephaly 6 (4.6) other 39 (29.5) ct scan results normal 93 (71.0) elevated icp 38 (29.0) ophthalmoscopy widening of optic nerve 91 (69.5) blurring of optic disk 22 (16.9) elevation of optic disks 84 (64.6) hemorrhage over optic disk 3 (2.3) retinal venous tortuosity 14 (10.8) ct scan: computer tomography scan; icp: intracranial pressure; ivh: intraventricular hemorrhage; ich intracerebral hemorrhage. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com ebrahim zadeh et al 56 results: we enrolled 131 patients with positive ophthalmoscopy signs of icp rising (mean ± standard deviation of patients age 46.29 ± 10.0 years; 77.1% male). pseudo-tumor cerebri (20.2%), epilepsy (11.4%), cerebral vein thrombosis (9.9%), loss of conciseness (8.4%), intraventricular and intracerebral hemorrhage (8.4%), subarachnoid hemorrhage (7.6%), and hydrocephaly (4.6%) were the frequent etiology of icp rising. brain ct scan confirmed 38 (29.0%) cases of icp rising (table 1). auc of ophthalmoscopy was 0.68 (95% ci: 0.63-0.73). based on roc analysis, presence of at least one sign in ophthalmoscopy was defined as elevated icp. therefore, the number of diagnosed elevated icps with this criterion was 98 (74.8%) cases. the calculated sensitivity and specificity of ophthalmoscopy, with presence of at least one of the above-mentioned icp rising signs, were 100.0% (95% ci: 88.6-100.0) and 35.4% (95% ci: 26.046.2), respectively (figure 1). ultrasound examination revealed that mean right and left onsd were 5.5 ± 0.9 (range: 3.8 8.7) and 5.5 ± 1.0 (range: 2.0 8.6) millimeters, respectively. roc analysis of ultrasound examination revealed that auc of this method was 0.75 (95% ci: 0.66 0.84) (figure 2). considering the cutoff point of 5 millimeters, finally 102 patients (77.9%) were categorized in the elevated icp group, based on onsd. sensitivity and specificity of ultrasonography in prediction of elevated icp were 100.0% (95% ci: 84.0 100.0) and 31.9% (95% ci: 23.0 41.7), respectively (table 2). discussion: elevated icp is one of the main reasons of mortality in patients referred to the ed. regardless of its etiology, the immediate diagnosis and treatment of this condition can strongly improve the prognosis of the patients (2, 3). several methods are being used to evaluate patients with table 2: diagnostic accuracy of ultrasonography and ophthalmoscopy in prediction of elevated icp diagnostic value (%) test (95% confidence interval) ultrasonography ophthalmoscopy prevalence 29.0 (21.6 37.8) 29.0 (21.6 37.7) true positive 37.2 (28.0 47.4) 38.8 (29.3 49.2) true negative 100.0 (85.4 100.0) 100.0 (87.0 100.0) false positive 62.7 (52.6 71.9) 61.2 (50.8 70.7) false negative 0.0 (0.0 14.6) 0.0 (0.0 13.0) sensitivity 100.0 (88.6 100.0) 100.0 (88.6 100.0) specificity 31.2 (22.2 41.7) 35.5 (26.0 46.2) positive predictive value 37.3 (28.0 47.4) 38.8 (29.3 49.2) negative predictive value 100.0 (85.4 100.0) 100.0 (87.0 100.0) positive likelihood ratio 0.6 (0.4 0.8) 0.6 (0.5 0.9) negative likelihood ratio nan nan the entry "nan" in any of the above cells means that the calculation cannot be performed because entered values include one o r more instances of zero; icp: intracranial pressure. figure 1: receiver operating characteristic (roc) of ophthalmoscopy in detection of elevated intracranial pressure. figure 2: receiver operating characteristic (roc) of ultrasonography in detection of elevated intracranial pressure. cut off: the presence of at least one abnormal sign of icp rising 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n s it iv it y 0.00 0.25 0.50 0.75 1.00 1 specificity area under roc curve = 0.7162 cut off > 5 mm 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n s it iv it y 0.00 0.25 0.50 0.75 1.00 1 specificity area under roc curve = 0.7521 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 57 emergency (2015); 3 (2): 54-58 probable elevated icp, including clinical assessment and use of physical examination, laboratory studies, inspection of the ocular signs of increased icp, and imaging studies (7, 13, 14). based on the results of the present study, sensitivity of ultrasonography in prediction of icp elevation was 100.0%, while its specificity was low (23.7%). meanwhile, the diagnostic accuracy of onsd was similar to ophthalmoscopy (sensitivity=100.0; specificity=35.5). ophthalmodynamometry has been shown to be efficient for icp assessment, while for continuous monitoring of icp other measurements should be taken (15). in two of their studies, amini et al. demonstrated that ultrasonography examination of optic nerve sheath could be considered as an available, accurate, and noninvasive screening tool for determining the elevated intracranial pressure in cases with head trauma or cerebrovascular accident (12, 16). in contrast, caffery et al. showed that sensitivity of optic nerve sheath diameter in detection of elevated icp is 75%. these authors concluded that it is not an adequate screening tool for detection of non-traumatic causes of icp elevation (17). one explanation for the differences between our results and the findings of caffery et al. may be methodological. they only examined non-traumatic causes of icp rising, but we assessed patients with all causes. the meta-analysis suggested that ultrasonography of optic nerve had a good level of diagnostic accuracy for detecting icp rising. it may aid in clinical decision-making and triage of patients for transferring them to specialized centers (11). rajajee et al. suggested that optic nerve diameter, equal to or greater than 0.48 centimeter, has the greatest accuracy in diagnosis of raised icp (18). the present study revealed that presence of at least one of the ophthalmoscopy abnormalities, including widening of optic nerve disk, ocular venous engorgement, blurring, hemorrhage over optic disk, elevation of optic disk, and retinal venous tortuosity might predict the presence of icp elevation. similar to this results, mena et al. demonstrated that the rise in icp leads to marked hemorrhage within the optic nerve sheath as well as intraand preretinal hemorrhages (19). nevertheless, association of raised intracranial pressure with ophthalmic findings was not fully understood. therefore, further study is recommended to investigate and explain its exact mechanism. one limitation of our study was the fact that we used helical ct scan, which has less accuracy than spiral ones. moreover, the studied patients had various etiologies of icp rising including head trauma, subarachnoidal hemorrhage, space-occupying lesions, hydrocephalous, metabolic disorders, and electrolyte imbalance that could affect the outcomes. conclusion: the present study revealed that bedside ultrasonography of optic nerve sheath and ophthalmoscopy have enough accuracy for the screening of patients with probable elevation of icp. of course, it should be considered that despite the high sensitivity of both tools, their specificity is low. acknowledgments: the authors appreciate the insightful cooperation of the staff of the emergency department of alzahra hospital. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. kalantari h, jaiswal r, bruck i, et al. correlation of optic nerve sheath diameter measurements by computed tomography and magnetic resonance imaging. am j emerg med. 2013;31(11):1595-7. 2. arbour r. intracranial hypertension monitoring and nursing assessment. crit care nurse. 2004;24(5):19-32. 3. tayal vs, neulander m, norton hj, foster t, saunders t, blaivas m. emergency department sonographic measurement of optic nerve sheath diameter to detect findings of increased intracranial pressure in adult head injury patients. ann emerg med. 2007;49(4):508-14. 4. czosnyka m, pickard jd. monitoring and interpretation of intracranial pressure. j neurol neurosurg psychiatry. 2004;75(6):813-21. 5. schaller b, graf r. different compartments of intracranial pressure and its relationship to cerebral blood flow. j trauma. 2005;59(6):1521-31. 6. raboel p, bartek j, andresen m, bellander b, romner b. intracranial pressure monitoring: invasive versus noninvasive methods—a review. crit care res pract. 2012;2012:14. 7. rothwell p, gibson r, sellar r. computed tomographic evidence of cerebral swelling in benign intracranial hypertension. j neurol neurosurg psychiatry. 1994;57(11):1407-9. 8. kimberly hh, noble ve. using mri of the optic nerve sheath to detect elevated intracranial pressure. crit care. 2008;12(5):181. 9. mizrachi ib-b, trobe jd, gebarski ss, garton hj. papilledema in the assessment of ventriculomegaly. j neuroophthalmol. 2006;26(4):260-3. 10. malayeri aa, bavarian s, mehdizadeh m. sonographic evaluation of optic nerve diameter in children with raised intracranial pressure. j ultrasound med. 2005;24(2):143-7. 11. dubourg j, javouhey e, geeraerts t, messerer m, kassai b. ultrasonography of optic nerve sheath diameter for detection of raised intracranial pressure: a systematic review and metaanalysis. intensive care med. 2011;37(7):1059-68. 12. amini a, eghtesadi r, feizi am, et al. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. emergency. 2013;1(1):15-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com ebrahim zadeh et al 58 13. kimberly hh, shah s, marill k, noble v. correlation of optic nerve sheath diameter with direct measurement of intracranial pressure. acad emerg med. 2008;15(2):201-4. 14. hergenroeder gw, moore an, mccoy jp, et al. serum il-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury. j neuroinflammation. 2010;7(1):19. 15. motschmann m, müller c, kuchenbecker j, et al. ophthalmodynamometry: a reliable method for measuring intracranial pressure. strabismus. 2001;9(1):13-6. 16. amini a, kariman h, arhami dolatabadi a, et al. use of the sonographic diameter of optic nerve sheath to estimate intracranial pressure. am j emerg med. 2013;31(1):236-9. 17. caffery ts, perret jn, musso mw, jones gn. optic nerve sheath diameter and lumbar puncture opening pressure in nontrauma patients suspected of elevated intracranial pressure. am j emerg med.[in press]. 18. rajajee v, vanaman m, fletcher j, jacobs t. optic nerve ultrasound for the detection of raised intracranial pressure. neurocrit care. 2011;15(3):506-15. 19. mena oj, paul i, reichard rr. ocular findings in raised intracranial pressure: a case of terson syndrome in a 7month-old infant. am j forensic med pathol. 2011;32(1):55-7. archives of academic emergency medicine. 2023; 11(1): e60 le t t e r to ed i to r enhancing emergency response through artificial intelligence in emergency medical services dispatching; a letter to editor payam emami1∗, karim javanmardi2 1. department of emergency medical sciences, faculty of paramedical sciences, kurdistan university of medical sciences, sanandaj, iran. 2. education and research unit, emergency medical service and disaster management center, urmia, iran . received: june 2023; accepted: july 2023; published online: 22 august 2023 cite this article as: emami p, javanmardi k. enhancing emergency response through artificial intelligence in emergency medical services dispatching; a letter to editor. arch acad emerg med. 2023; 11(1): e60. https://doi.org/10.22037/aaem.v11i1.2097. dear editor the emergency medical dispatcher (emd) serves as a crucial link between individuals in need of emergency medical assistance and the emergency medical services (ems) resource delivery system. through their expertise and training, emds are able to accurately assess emergency situations, provide appropriate guidance over the phone, and dispatch the necessary ems personnel to the scene. with adequate training, program management, supervision, and medical guidance, the emd can accurately assess the caller’s needs, choose an appropriate response approach, furnish relevant information to responders, and offer suitable assistance and guidance to patients through the caller. by diligently adhering to a written and medically approved emd protocol, informed decisions regarding ems responses can be made in a reliable, replicable, and fair manner (1, 2). artificial intelligence (ai) is the concept of a computer program that utilizes existing information to make decisions and enhances its performance based on accumulated experience. machine learning (ml), a crucial aspect of ai, focuses on developing systems that learn from past data to create models for classification, clustering, or regression. ml algorithms excel at recognizing patterns in intricate datasets, making them valuable for interpreting outcomes and generating personalized clinical judgments (3). in recent years, advancements in ai have made a significant impact on various industries, and ems is no exception. ai has the potential to revolutionize the way emergency medical dispatching is conducted, improving response times, accuracy, and ultimately, ∗corresponding author: payam emami; department of emergency medical sciences, faculty of paramedical sciences, kurdistan university of medical sciences, sanandaj, iran. email: p.emami@muk.ac.ir, tel: +989188786115 , orcid: https://orcid.org/0000-0002-1892-7539. patient outcomes (4, 5). ai has the potential to revolutionize how emergency calls are managed and responded to, ultimately improving the quality and efficiency of emergency medical care. traditionally, ems dispatching has relied on human operators to receive emergency calls, assess the situation, and dispatch appropriate resources. however, this process can be time-consuming and prone to human error, especially during high-pressure situations like out-of-hospital cardiac arrest when quick decisions are crucial (5). ai-driven dispatching systems, equipped with natural language processing and machine learning capabilities, can analyze and prioritize incoming emergency calls based on the severity and urgency of the situation. these systems can identify key information, such as location, symptoms, and available resources, and provide real-time recommendations for dispatching appropriate medical teams or resources (6). by leveraging ai, emergency call centers can optimize resource allocation, leading to faster response times and improved patient outcomes. ai algorithms can analyze historical data and ongoing trends to predict demand patterns, enabling better deployment of ems units and reducing response time variability. additionally, ai can assist in identifying potential cardiac events, strokes, or other medical emergencies by analyzing voice patterns or vital signs shared during emergency calls, facilitating early intervention and potentially saving lives (7, 8). ml system is able to recognize a higher proportion of out-ofhospital cardiac arrest (ohca) cases within the first minute compared to human dispatchers. ml system has the potential to be a useful tool in emergency calls (9). it is important to emphasize that while ai can improve emergency dispatching, it should always complement, not replace, the human element. trained professionals will continue to play a critical role in decision-making and providing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index p. emami and k. javanmardi 2 empathetic support during emergencies. ai should be seen as a powerful tool to enhance their capabilities rather than a substitute for their expertise. as ai continues to advance, it is crucial for emergency medical services and policymakers to embrace these technologies responsibly. safeguards must be in place to ensure data privacy, transparency, and ongoing monitoring of ai systems to mitigate biases and ensure equitable emergency response (5, 6). 1. conclusion the integration of ai in ems dispatching has the potential to revolutionize emergency care by optimizing resource allocation, reducing response times, and ultimately saving lives. it is imperative that we invest in research, implementation, and ongoing evaluation to maximize the benefits of ai while upholding ethical guidelines and maintaining the human touch in emergency medical services. 2. declarations 2.1. acknowledgments none. 2.2. conflict of interest the authors declare that they have no conflict of interest. 2.3. funding and support this research received no specific grant from any funding agencies in the public, commercial, or non-profit sectors. 2.4. authors’ contribution pe and kj: conception and design of the work. pe: drafting the work and revising it critically for important intellectual content and translation. pe and kj: read and approved the final version and accountable for all aspects of the work. 2.5. data availability not applicable. 2.6. using artificial intelligence chatbots not used in this article. references 1. crabb db, elmelige yo, gibson zc, ralston dc, harrell c, cohen sa, et al. unrecognized cardiac arrests: a one-year review of audio from emergency medical dispatch calls. am j emerg med. 2022; 54:127-30. 2. dong x, ding f, zhou s, ma j, li n, maimaitiming m, et al. optimizing an emergency medical dispatch system to improve prehospital diagnosis and treatment of acute coronary syndrome: nationwide retrospective study in china. j med internet res. 2022;24(11): e36929. 3. ledziński ł, grześk g. artificial intelligence technologies in cardiology. j cardiovasc dev dis. 2023;10(5). 4. bajwa j, munir u, nori a, williams b. artificial intelligence in healthcare: transforming the practice of medicine. future health j. 2021;8(2): e188-e94. 5. scholz ml, collatz-christensen h, blomberg snf, boebel s, verhoeven j, krafft t. artificial intelligence in emergency medical services dispatching: assessing the potential impact of an automatic speech recognition software on stroke detection taking the capital region of denmark as case in point. scand j trauma resusc emerg med. 2022;30(1):36. 6. chenais g, lagarde e, gil-jardiné c. artificial intelligence in emergency medicine: viewpoint of current applications and foreseeable opportunities and challenges. j med internet res. 2023;25:e40031. 7. bohr a, memarzadeh k. the rise of artificial intelligence in healthcare applications. artificial intelligence in healthcare: elsevier; 2020:25-60. 8. chang i, lee sc, do shin s, song kj, ro ys, park jh, et al. effects of dispatcher-assisted bystander cardiopulmonary resuscitation on neurological recovery in paediatric patients with out-of-hospital cardiac arrest based on the prehospital emergency medical service response time interval. resuscitation. 2018;130:49-56. 9. byrsell f, claesson a, ringh m, svensson l, jonsson m, nordberg p, et al. machine learning can support dispatchers to better and faster recognize out-of-hospital cardiac arrest during emergency calls: a retrospective study. resuscitation. 2021;162:218-26. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 114 emergency (2015); 3 (3): 114-116 brief report diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report ali taghizadieh1, alireza ala2, farzad rahmani3*, akbar nadi4 1. tuberculosis and lung disease research center, tabriz university of medical sciences, tabriz, iran. 2. emergency medicine department, tabriz university of medical sciences, tabriz, iran. 3. road traffic injury research center, tabriz university of medical sciences, tabriz, iran 4. students’ research committee, tabriz university of medical sciences, tabriz, iran *corresponding author: farzad rahmani; emergency medicine department, imam reza hospital, tabriz university of medical sciences, 5166614756, tabriz, iran. tel:+984113352078; fax: +984113352078; email: rahmanif@tbzmed.ac.ir received: november 2014; accepted: january 2015 abstract introduction: chest x-ray (cxr) is the simplest diagnostic tool of community acquired pneumonia (cap), but it has some limitation. therefore, the aim of this study is comparing the diagnostic accuracy of cxr and chest ultrasonography (cus) in detection of cap. methods: in the present study, a consecutive sample of suspected patients with cap was underwent cus, cxr, and chest computed tomography (ct) scan. diagnostic accuracy of cus and cxr was assessed by calculating the sensitivity, specificity, predictive values, and likelihood ratios using spss 20 statistical software. results: 30 patients with cap were enrolled (93.3% male with mean age of 63.8 ± 18.3 years). sensitivity of cus and cxr in detection of cap were 100.0% (95% cl: 85.4-100.0) and 93.1% (95% cl: 75.8-98.8), respectively. specificity of cxr was 0.0 (95% cl: 0.0-94.5), while the cus specificity was not calculable. conclusion: findings of the present study demonstrated on the higher diagnostic accuracy of cus versus cxr in detection of pneumonia. key words: pneumonia; ultrasonography; emergency department; radiography, thoracic; tomography, x-ray computed cite this article as: taghizadieh a, ala a, rahmani f, nadi a. diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report. emergency. 2015;3(3):114-16 introduction: ommunity acquired pneumonia (cap) is one of the main concerns of health services which only causes to 1.7 million cases of hospitalization annually in the united states (1, 2). it is one of the most common infectious diseases and important causes of mortality and morbidity in worldwide (3). streptococcus pneumonia, hemophilic influenza, and moraxella catarrhalis are typical bacterial pathogens in approximately 85% of cap cases (4). the presentation of cap includes fever, cough, and pleuritic chest pain. beside the physical examination, chest x-ray (cxr), as the simplest diagnostic tool, is suggested to exclude conditions mimic cap (1). however, cxr findings may be negative in patients if cap presents at early stages of the disease. moreover, noticing to high costs and the need for more irradiation, the routine usage of computed tomography (ct) scan in diagnosis of pneumonia in emergency departments is not recommended (5). ultrasonography (cus) has been recently applied in detection of pulmonary diseases such as pulmonary edema, pulmonary embolisms, pericardial and pleural effusion, and pneumothorax (6, 7). however, only few data have been published to show its efficiency in detecting pneumonia. therefore, the aim of this study was evaluating diagnostic accuracy of cxr and cus in findings of pneumonia. methods: study design and setting the present study was conducted to evaluate diagnostic accuracy of cus and cxr in detection of pneumonia. it was performed in the emergency department (ed) of imam reza medical research and training hospital, tabriz, east azerbaijan, iran, through february to april 2014. the local ethical committee of tabriz university of medical sciences approved the protocol of the study and written consent was obtained from all patients after describing the aims and methods of the study. the consecutive samples of suspected cap patients were underwent cus, cxr, and ct scan. presence of fever, cough, pleuritic pain, sputum production, and dyspnea were considered as signs and symptoms of cap (8). patients with asthma, acute coronary syndrome, septic shock, c this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 115 emergency (2015); 3 (3): 114-116 pulmonary embolism, chronic obstructive pulmonary disease (copd), cardiac and pleural disorders were excluded. after clinical examinations, patients with clinical suspicion of cap underwent cxr, cus, and chest ct scan. clinical examinations and cus were done with bedside machine available in the ed (gh healthcare; logiq 200, pro series; korea) with a convex 3.5-mhz transducer by a trained emergency medicine specialist. then, patient referred to radiology unit to perform cxr and chest ct scan (as a gold standard) with toshiba asteion 16 slices scanner with considering one-millimeter distance between image slices. the radiography and ct scan findings were interpreted by a radiologist blinded to clinical examinations. data was analyzed using spss 20 software. diagnostic accuracy of cus and cxr were assessed by calculating the sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. results: we studied imaging findings of 30 patients with clinical suspicion of community-acquired pneumonia (93.3% male, mean age 63.8±18.3 years). ct scan findings showed 29 (96.7%) cases of pneumonia, while cus revealed the diagnosis of pneumonia for all 30 cases (1 case of false positive). cxr also showed 28 (93.3%) pneumonia cases (2 false negative and 1 false positive) (table1). the sensitivity of cus in pneumonia detection was calculated 100.0% (95% ci: 85.4-100.0), but its specificity was not calculable because of being positive of all subjects. however, sensitivity and specificity of cxr in pneumonia detection were 93.1% (95% ci: 75.898.8) and 0.0% (95% ci: 0.0-94.5), respectively. based on ct scan findings, finally 13 (43.3%) cases had evidence of pleural effusion. cus detected 12 (40%) subjects (1 false negative), while cxr could only detect 8 (26.7%) patients (4 false positive and 4 false negative). sensitivity and specificity of cus in detection of pleural effusion were 92.3% (95% ci: 62.1-99.6) and 100.0% (95% ci: 77.1-100.0), respectively. sensitivity and specificity of cxr were also 66.7% (95% ci: 35.4-88.7) and 77.8% (95% ci: 51.9-92.6), respectively (table 1). discussion: findings of the present study demonstrated that diagnostic accuracy of cus in detection of pneumonia and plural effusion were higher than cxr. several studies stated that cus is a simple, fast, and effective diagnostic tool for detection of pulmonary diseases. for example, in a study done by mathis and colleagues, authors recommended that ultrasonography is the simplest and most sensitive imaging tool for measurement of pleural fluid (9). bsrilleni and colleagues concluded that ultrasonography is a useful and reliable method in diagnosing the pulmonary diseases (10). in another study conducted by lichtenstein et al., it was stated that cus is a fast and cost effective method in detecting pulmonary diseases, without radiation exposure (11). neesse and colleagues evaluated the results of cxr in pulmonary diseases and concluded that ultrasonography is a rapid tool in detecting the pulmonary diseases, leads to accurate diagnosis in 68% of cases (12). these findings are along with advanced trauma life support (atls), represented that ultrasonography can be used in detection of abdominal free fluid, organ trauma, and pneumothorax. however, it should be considered that ultrasonography is highly operator dependent. one of the most important solving is the exact and long-term training of ed specialists regarding performing and interpreting of ultrasonography finding. the small sample size was the limitation of this study and consequently specificity of cus was not calculable. in addition, the small sample size caused that no true negative case was seen by cxr; therefore, the power of table 1: diagnostic accuracy of chest ultrasonography and radiography in detection of pneumonia and plural effusion (95% confidence interval) diagnostic test pneumonia plural effusion ultrasonography sensitivity 100.0 (85.4-100.0) 92.3 (62.1-99.6) specificity nan 100.0 (77.1-100.0) positive predictive value 100.0 (85.4-100.0) 100.0 (70.0-100.0) negative predictive value 0.0 (0.0-14.5) 94.4 (70.6-99.7) positive likelihood ratio nan nan negative likelihood ratio nan 0.08 (0.01-0.5) radiography sensitivity 93.1 (75.8-98.8) 66.7 (35.4-88.7) specificity 0.0 (0.0-94.5) 77.8 (51.9-92.6) positive predictive value 96.4 (79.8-99.8) 66.7 (35.4-88.7) negative predictive value 0.0 (0.0-80.2) 77.8 (51.9-92.6) positive likelihood ratio 0.93 (0.84-1.03) 3.0 (1.2-7.8) negative likelihood ratio nan 0.4 (0.2-1.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com taghizadieh et al 116 calculated specificity of cxr was week. the cus operator was not blind to the clinical presentation of patients, while the radiologist did not aware from the clinical presentation of patients and less diagnostic accuracy of cxr might be derived from that. conclusion: finding of the present study demonstrates that diagnostic accuracy of cus in detection of pneumonia and plural effusion were higher than cxr. acknowledgments: the authors are grateful to all the health personnel, data collectors, supervisors, administrative staff of the emergency department of imam reza hospital, and patients participated in the study. this article was written based on a dataset of medical doctor thesis, registered in tabriz university of medical sciences. conflict of interest: none funding support: none authors’ contributions: all authors have read and approved the manuscript .ali taghizadieh, alireza ala, and akbar nadi performed the data collection, literature review, and drafting of the manuscript. farzad rahmani undertook the major parts of the study design and performed the statistical analysis. references: 1. spellberg b. community-acquired pneumonia. n engl j med. 2014;370(19):1861-2. 2. file jr tm. streptococcus pneumoniae and communityacquired pneumonia: a cause for concern. am j med supp. 2004;117(3):39-50. 3. solomon cg, wunderink rg, waterer gw. communityacquired pneumonia. n engl j med. 2014;370(6):543-51. 4. ellis a, kinasewitz g, matousek s. morbidity and mortality of severe sepsis patients with community acquired vs. health care associated pneumonia. am j respir crit care med. 2014;189:a3130. 5. llinares p, menéndez r, mujal a, navas e, barberán j. guidelines for the management of community-acquired pneumonia in the elderly patient. rev esp quimioter. 2014;27(1):69-86. 6. shojaee m, faridaalaee g, yousefifard m, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chin j traumatol. 2014;17(1):19-24. 7. heydari f, esmailian m, dehghanniri m. diagnostic accuracy of ultrasonography in the initial evaluation of patients with penetrating chest trauma. emergency. 2014;2(2):77-80. 8. mandell la, wunderink rg, anzueto a, et al. infectious diseases society of america/american thoracic society consensus guidelines on the management of communityacquired pneumonia in adults. clin infect dis. 2007;44(supplement 2):s27-s72. 9. mathis g, gehmacher o. lung and pleural ultrasound. praxis. 2001;90(16):681-6. [german]. 10. barillari a, fioretti m. lung ultrasound: a new tool for the emergency physician. intern emerg med. 2010;5(4):335-40. 11. lichtenstein da. ultrasound in the management of thoracic disease. crit care med. 2007;35(5):s250-s61. 12. neesse a, jerrentrup a, hoffmann s, et al. prehospital chest emergency sonography trial in germany: a prospective study. eur j emerg med. 2012;19(3):161-6. emergency. 2017; 5 (1): e78 doi: http://dx.doi.org/10.22037/emergency.v5i1.18497 or i g i n a l re s e a rc h demographics of fall-related trauma among the elderly presenting to emergency department; a cross-sectional study hamid reza morteza bagi1, sajjad ahmadi2∗, maryam hosseini3 1. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. 2. emergency medicine department, maragheh university of medical sciences, maragheh, iran. 3. faculty of medicine, tabriz university of medical sciences, tabriz, iran. received: august 2017; accepted: august 2017; published online: 12 september 2017 abstract: introduction: falling is reported to be the most common cause of mortality due to trauma in individuals over the age of 75 years. the present study is designed with the aim of determining the demographics of fall-related trauma among the elderly presenting to emergency department (ed). methods: the present prospective crosssectional study was carried out on all elderly patients ≥ 60 years old presenting to ed of a major referral trauma center in north west of iran during 1 year. demographic data, location and height of falling, duration of hospitalization, trauma severity and in-hospital outcome of the patients were gathered and reported via descriptive statistics. results: 228 patients with the mean age of 70.96 ± 5.2 years were studied (53.9% female). most patients were in the 66-70 years age range (32.6%) and had a history of hypertension (22.3%), who had visited following a fall inside the house (69.3%), due to slipping (73.7%), and from a height equal to or less than 2m (71.9%). 6 (2.6%) patients died in the hospital. mean trauma severity of patients based on iss, rts, and triss were 10.65 ± 3.95 (3-19), 7.84 ±.21 (1.4-14.5) and 1.66 ±1.31 (-1.49-3.82), respectively. regarding need for hospitalization, only iss shows a significant difference between outpatients and inpatients (p = 0.023). patients who died had a significantly higher trauma severity based on iss (p < 0.0001) and rts (p < 0.0001). conclusion: based on the findings of the present study, slipping and syncope are the most common causes of falling in the studied elderly that had mostly happened inside the house and from a height less than 2m. therefore, most patients were in the mild to moderate range of trauma severity. iss and rts were significantly higher in the 6 (2.6%) patients who died. keywords: trauma severity indices; accidental falls; aged; demography; cross-sectional studies © copyright (2017) shahid beheshti university of medical sciences cite this article as: morteza bagi h, ahmadi s, hosseini m. demographics of fall-related trauma among the elderly presenting to emergency department; a cross-sectional study. emergency. 2017; 5(1): e78. 1. introduction i ncrease in life expectancy has led to a rise in the number of elderly individuals all over the world and aging has become one of the most important challenges of public health in various countries. due to their lower activity, old people are less likely to face injuries but if they get injured they have a higher mortality rate compared to young peo∗corresponding author: dr. sajjad ahmadi; department of emergency medicine, amiralmomenin hospital, north moallem _ nova road, maragheh, iran. postal code: 55391-41416 e-mail: dr.ahmadi96993@gmail.com tel: 009837241597 ple because of disorders in physiological functions and body systems as well as presence of other medical problems. currently, trauma is the 5th cause of death among elderly people and falling is the most common cause of mortality due to trauma in individuals over the age of 75 years (1-3). in total, falling leads to about 40% of deaths due to trauma in old people (4). 20% to 28% of the elderly in iran experience falling, and fear of falling leads to limited activity in 30% of old people (5, 6). falling makes up 10-15% of emergency department (ed) visits (4, 7, 8) and its outcome in old people varies from complete recovery to death. duration of hospitalization among the elderly also ranges from a few days to being permanently crippled (9-15). it seems that planning on this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. morteza bagi et al. 2 prevention of the accident is the best and most cost effective measure in this regard. however, any planning requires information on the epidemiologic characteristics and the situation of the subject of planning. therefore, the present study is designed with the aim of determining the demographics of fall-related trauma among the elderly presenting to ed. 2. methods 2.1. study design and setting the present prospective cross-sectional study was carried out on elderly patients (≥ 60 years old) presenting to ed of imam reza hospital, tabriz, iran, following trauma caused by falling, from april 2015 to march 2016 (during 1 year). this hospital is one of the major referral trauma centers in north west of iran. the study was approved by the ethics committee of tabriz university of medical sciences and the researchers adhered to principles of helsinki declaration and keeping patient data confidential. oral consent was obtained from the patients for participating in the study. 2.2. participants all patients, 60 years old or older, who had visited the trauma unit of the mentioned ed during the study period following falling and were willing to participate were included via consecutive sampling. patients who had died before arriving at the ed or were discharged against medical advice (71 patients), were excluded from the study. 2.3. data gathering a checklist consisting of baseline characteristics (age, sex, underlying illnesses), location of falling, height of falling, duration of hospitalization, data required for calculation of trauma severity based on injury severity score (iss), revised trauma score (rts), and trauma and injury severity score (triss), and in-hospital mortality was filled for all the patients. the person in charge of data gathering and calculation of trauma severity was a senior emergency medicine resident, under supervision of the corresponding attend. iss is calculated based on the severity of trauma to face, head, extremities, chest, and abdomen (13). if this score is equal to or higher than 16, the patient is deemed multiple trauma (14, 15). an iss lower than 7, indicates mild physical injury, 7-12 moderate injury and more than 12 shows severe injury. in rts, trauma severity is calculated based on level of consciousness, systolic blood pressure and respiratory rate and is also used for triage of the patients (16). triss indicates the prognosis of trauma patients and acts based on the physiologic and anatomic status of the patient on admission to ed. this system of determining trauma severity is in fact a combination of iss and rts (17). table 1: baseline characteristics of the studied patients variable number (%) sex male 105 (46.1) female 123 (53.9) age (year) 60 – 65 39 (17.1) 66 – 70 74 (32.6) 71 – 75 64 (28.1) 76 – 80 45 (19.7) > 80 6 (2.6) underlying disease hypertension 51 (22.3) ischemic heart disease 22 (9.6) osteoporosis 23 (10.1) diabetes 12 (5.2) neurologic disease 12 (5.2) none 125 (54.8) duration of hospitalization outpatient 88 (38.6) < 5days 98 (43.0) > 5 days 42 (18.4) table 2: accident characteristics of the studied patients variable number (%) location of fall outside the house 70 (30.7) bathroom 47 (20.6) kitchen 45 (19.7) steps 34 (14.9) other 32 (14.0) cause of fall slipping 168 (73.7) altered level of consciousness 51 (22.4) other 9 (3.9) height of fall (m) ≥ 2 134 (71.9) > 2 49 (21.5) unknown 15 (6.6) 2.4. statistical analysis data were analyzed by spss version 21. quantitative data are reported as mean and standard deviation and qualitative ones are reported as frequency and percentage. to compare 2 groups, t-test and chi square tests were used and to calculate trauma severity based on the mentioned indices, medical calculator was used. significance level in analyses was considered to be less than 0.05. 3. results 3.1. baseline characteristics 228 patients with the mean age of 70.96 ± 5.2 years were studied (53.9% female). tables 1 and 2 depict the baseline charthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e78 table 3: comparison of mean trauma severity between inpatients and outpatients as well as dead and alive patients based on iss, rts and triss indices variable trauma severity (mean ± standard deviation) iss p value rts p value triss p value hospitalization outpatient 9.9 ± 3.41 0.023 7.96 ± 2.42 0.295 1.52 ± 1.40 0.453 inpatient 11.12 ± 4.20 7.64 ± 1.83 1.65 ± 1.23 mortality alive 10.55 ± 3.92 0.0001 7.86 ± 2.23 0.0001 1.60 ± 1.31 0.406 dead 20.66 ± 6.68 13.50 ± 1.00 2.05 ± 0.91 acteristics of the patients and fall characteristics. according to these results, most patients were in the 66-70 years age range (32.6%) and had a history of hypertension (22.3%), who had visited following a fall inside the house (69.3%), due to slipping (73.7%), and from a height equal to or less than 2m (71.9%). 6 (2.6%) patients died in the hospital and others were discharged from ed (38.6%) or from surgery department after a few days of hospitalization (61.4%). 3.2. trauma severity mean trauma severity of patients based on iss, rts, and triss were 10.65 ± 3.95 (3-19), 7.84 ±.21 (1.4-14.5) and 1.66 ±1.31 (-1.49-3.82), respectively. trauma severity based on iss was less than 7 in 60 (26.3%) patients, between 7 and 12 in 98 (43.0%) and over 12 in 70 (30.7%) injured patients. table 3 compares mean trauma severity of the patients based on the 3 mentioned indices between patients who survived and those who died as well as outpatients and inpatients. as can be seen, only iss shows a significant difference between outpatients and inpatients (p = 0.023). in addition, patients who died had a significantly higher trauma severity based on iss (p < 0.0001) and rts (p < 0.0001). 4. discussion based on the findings of the present study, slipping and syncope were the most common causes falling in the studied elderly, who had mostly fallen from a height less than 2m and inside the house. most patients were in the mild to moderate range of trauma severity. iss and rts were significantly higher in the 6 (2.6%) patients who had died. statistics show that each year on average 28 to 35% of the elderly over 60 years old fall and in those over the age of 70 years this rate rises to 32 to 42% and in half of the cases, it happens recurrently. this emphasizes the necessity of taking preventive measures and applying plans to prevent this from happening again (18, 19). in a study carried out in 2004 by schoenfelder et al., falling rate was higher in women compared to men (82.10% versus 17.90%) (4). swanenburg et al. in 2010 also reported the higher prevalence of this problem in women (83% vs. 17%) (20). however, in the present study affected men and women were relatively equal. in corsinovi et al. study on 620 elderly patients that were treated following a fall, no correlation was found between age and falling rate (14). regarding quantitative trauma severity, findings showed that mean iss was 10.67 and most patients had moderate injury. in a study by zare et al. evaluating trauma in emergency patients whose mean age was 29.60 years, the results showed that quantitative trauma severity was 16.98, which can show the higher severity of trauma and risky behaviors in young people compared to the elderly (21). in 2009, hariharan et al. evaluated the clinical value of triss in 326 trauma patients. mean survival rate in adults was reported to be 98.50% in the study, which indicates 1.5% mortality in these patients. these researchers concluded that triss was not so accurate in predicting the prognosis of trauma patients (22). in addition in 2004, murlidhar et al. evaluated triss in a study of trauma patients’ outcome and reported that the predicted mortality rate in patients by this index was 10.89%. this rate was 61.60% and 16.60% for rts and iss, respectively but the real mortality rate was 21.26%. the researchers reported the cause of this vast difference to be the higher age of the patients studied compared to other studies (23). meanwhile, in another study conducted by mitchell et al. in 2007 in canada the ability of indices such as triss to predict the prognosis of trauma patients were evaluated and shown to be acceptable (24). the obtained results regarding trauma severity indices showed that triss did not correlate with hospitalization status and mortality of the patients; however, iss correlated with hospitalization status and both iss and rts correlated with mortality of the patients. studies show that falling happens following a complex interference of risk factors that affect the health status of an elderly individual, directly or indirectly. these factors are categorized in 4 groups: biological, behavioral, environmental, and socioeconomic factors (18). although in this study, these factors were not evaluated individually, the evidence shows that evaluating and controlling these factors is of great imthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. morteza bagi et al. 4 portance. 5. limitation small sample size, being single-centered and the evaluated variables being few could be counted as the limitations of this study. however, considering the limited number of these studies in iran, the findings of this study can help in understanding the conditions ruling trauma due to falling in the elderly. 6. conclusion based on the findings of the present study, slipping and syncope are the most common causes of falling in the studied elderly that had mostly happened inside the house and from a height less than 2m. therefore, most patients were in the mild to moderate range of trauma severity. iss and rts were significantly higher in the 6 (2.6%) patients who died. 7. appendix 7.1. acknowledgements all the ed staff members are acknowledged for cooperating during the project. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest hereby, 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2004;35(4):386-90. 24. mitchell ad, tallon jm, sealy b. air versus ground transport of major trauma patients to a tertiary trauma centre: a province-wide comparison using triss analysis. can j surg. 2007;50(2):129. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e1 or i g i n a l re s e a rc h extracting the factors affecting the survival rate of trauma patients using data mining techniques on a national trauma registry mehdi nasr isfahani1,2, nahid tavakoli3, hossein bagherian4, neda al sadat fatemi1,2, mohammad sattari4∗ 1. trauma data registration center, isfahan university of medical sciences, isfahan, iran. 2. department of health in disasters and emergencies, school of management and medical informatics, isfahan university of medical sciences, isfahan, iran. 3. health management and economics research center, isfahan university of medical sciences, isfahan, iran. 4. health information technology research center, isfahan university of medical sciences, isfahan, iran. received: november 2022; accepted: december 2022; published online: 1 january 2023 abstract: introduction: thousands of people die due to trauma all over the world every day, which leaves adverse effects on families and the society. the main objective of this study was to identify the factors affecting the mortality of trauma patients using data mining techniques. methods: the present study includes six parts: data gathering, data preparation, target attributes specification, data balancing, evaluation criteria, and applied techniques. the techniques used in this research are all from the decision tree family. the output of these techniques are patterns extracted from the trauma patients dataset (national trauma registry of iran). the dataset includes information on 25,986 trauma patients from all over the country. the techniques that were used include random forest, chaid, and id3. results: random forest performs better than the other two techniques in terms of accuracy. the id3 technique performs better than the other two techniques in terms of the dead class. the random forest technique has performed better than other techniques in the living class. the rules with the most support, state that if the injury severity score (iss) is minor and vital signs are normal, 98% of people will survive. the second rule, in terms of support, states that if iss is minor and vital signs are abnormal, 93% will survive. also, by increasing the threshold of the patient’s arrival time from 10 to 15 minutes, no noticeable difference was observed in the death rate of patients. conclusion: transfer time of less than ten minutes in patietns whose iss is minor, can increase the chance of survival. impaired vital signs can decrease the chance of survival in traffic accidents. also, if the iss is minor in non-penetrating trauma, regardless of vital signs and if the victim is transported in less than ten minutes, the patient will survive with 99% certainty. keywords: data mining; survival; mortality; trauma severity indices; injuries; injury severity score cite this article as: nasr isfahani m, tavakoli n, bagherian h, fatemi nas, sattari m. extracting the factors affecting the survival rate of trauma patients using data mining techniques on a national trauma registry. arch acad emerg med. 2023; 11(1): e1. https://doi.org/10.22037/aaem.v11i1.1763. 1. introduction nowadays, most people are exposed to various accidents. thousands of people die due to these accidents all over the world every day, which leaves adverse effects on families and the society. these accidents can include disasters (natural ∗corresponding author: mohammad sattari; isfahan university of medical sciences, salamat boulevard, school of management and information, room 324, tel: +9831-37925152; email: msattarimng.mui@gmail.com, orcid: https://orcid.org/0000-0002-6091-4248. ,man-made), traffic accidents, and falls from a height (ffh). the outcome of such incidents on humans is called trauma, in case that is inflicted on the body from outside (1, 2). acute trauma such as motor vehicle collision (mvc), stab wounds, falls, and similar events can be fatal (3). early identification of trauma patients who are at risk of death is very important for clinical decision-making (4). data mining is one of the approaches that is used in various fields of medicine, including trauma management (5, 6). various researches have been done in this field. yadalhi’s study showed that the injury severity score (iss) index depicts an increase in trauma this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. nasr isfahani et al. 2 patients mortality rate. yet, an increase in the glasgow coma scale (gcs), and the revised trauma score (rts) and trauma injury severity score (triss) indices reduces the risk of mortality. it is worth mentioning that the triss index is better than other indices in assessing the severity of injury caused by trauma (7). hassanzadeh examined 1043 trauma patients and identified the factors affecting the mortality of patients. he used data mining techniques such as decision trees, k-nearest neighbors, and neural networks (8). liu used a review study to compare data mining techniques in predicting trauma outcomes. outcomes included survival/mortality, length of hospital stay, and traumatic brain injuries (9). rao investigated a model for predicting mortality from severe and moderate brain injury. he used logistic regression, support vector machine, decision tree, naive-bayes, and neural networks. the neural network had the best performance for predicting mortality due to trauma (10). trauma registries are one of the important sources of information that help check the quality of provided health care services. it also provides valuable perspectives to improve the quality of care (11). the main purpose of this study was to identify the factors affecting the survival of patients following trauma. this study aimed to identify the factors affecting the mortality of trauma patients using data mining techniques. 2. methods 2.1. study setting and design the study includes six parts: information collection, data preparation, specifying target attributes, data balancing, evaluation criteria, and applied techniques. the output of these techniques are patterns extracted from the trauma patients dataset (national trauma registry of iran). the dataset includes information on 25,986 trauma patients from all over the country. the techniques that were used include random forest, chaid, and id3. this study does not contain any studies with human participants or animals performed by any of the authors. the protocol of study was approved by ethics committee of isfahan university of medical sciences (ethical code: ir.mui.nurema.rec.1400.044). 2.2. data gathering eligibility criteria and sources and methods of selection of participants were: 1. trauma patients who were hospitalized for more than 24 hours. 2. trauma patients who died in the emergency department and were hospitalized for less than 24 hours. 3. trauma patients transferred from the previous hospital intensive care unit (icu) to current hospital icu with length of stay of less than 24 hours. the dataset includes information on 25,986 trauma patients from all over the country. the dataset was imbalanced so that the number of people who died was approximately 2% of the dataset and 98% of the victims were alive. the dataset had 132 attributes. after consulting with an emergency medicine specialist, the number of attributes was reduced to 23 items. these attributes include the patient’s age at the time of injury, iss, vital signs, the time interval between the occurrence of the injury and arrival at the emergency department (minutes), history of hospitalization due to trauma, the initial diagnosis of injury, cause of trauma, number of hospitalizations due to trauma, approximate height of the fall in meters, the position of the injured person, and if the victim is a nonpassenger, select the role of the injured person and the type of accident. when the type of accident was a collision, select the type of opposite object. if the injured person was a passenger in a car or motorcycle/bicycle, were appropriate safety devices used at the time of the accident? were safety belts used? if the injured person was a child younger than 8 years old in a car or motorcycle/bicycle, child seats; were appropriate safety devices used at the time of the accident? if the injured person was a passenger of a car, were appropriate safety devices such asairbags used when the accident occurred? if the injured person was a passenger of a motorcycle/bicycle, were appropriate safety devices such as helmets used when the accident occurred? in case of transfer between centers, was the patient transferred from another intensive care unit by ambulance to the current facility icu? what was the primary eye score (at the scene of the accident), the primary verbal score (at the scene of the accident), the primary motor score (at the scene of the accident), and initial total gcs (at the scene of the accident). 2.3. data preparation the iss attribute has numerical values. the values between 1 and 8 were categorized as minor, values 9 to 15 as moderate, values 16 to 24 as severe, and 25 and above as very severe. the attribute of the time interval between the occurrence of injury and reaching the emergency department (minutes) was divided into two periods of less than 10 minutes and more than 10 minutes. also, the age of the patient at the time of injury was divided into three periods: less than 8 years (children) and 8 to 18 years (adolescents), and more than 18 years (adults). records with missing values in more than 25 percent of attributes were removed. 2.4. identification of target attributes the survival attribute, which was a binary attribute, was used as the target attribute. the survival attribute had two values: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e1 survival and death. 2.5. balancing data the dataset was imbalanced. in order to avoid this variance to a feasible extent, it was necessary to use the bootstrap sampling technique (adaboost). 2.6. evaluation criteria the target group contains a binary class with two values, alive and dead. various criteria were used for evaluation. one of these criteria was accuracy. the closer the accuracy of this criterion, the better the result would be. this criterion was calculated based on the following formula: accuracy = (tp+tn)/(tp+tn+fp+fn) the tp (true positive) identifies the number of records that the group has correctly placed as dead. tn (true negative) identifies records that have been correctly identified as survived individuals. fn (false negative) identifies records that have been incorrectly identified as survived, and fp (false positive) identifies the number of records that have been incorrectly identified as dead. sensitivity (true positive rate) is the ratio of true predicted positive instances to the total of actual positive instances. these parameters can be calculated using equations: sensitivity=tp/(tp+fn) precison (positive predictive value) is the ratio of true predicted positive to the total of predicted positive instances. precsion = tp/(tp+fp) the support criterion specifies the number of repetitions of the combination of assumptions of a rule. the confidence criterion indicates for how many percent of people with the mentioned assumptions, the result is valid. in the evaluation stage, 25986 samples and 23 attributes are considered. the 10-fold cross-validation method was used to divide the dataset into training and test sets. based on this, the 25986 existing samples are divided into 10 groups. during 10 repetitions of the experiment, each time 9 groups make up 90% of the original dataset as the training dataset, and one remaining group makes up 10% of the original dataset, which is considered a test dataset. the training dataset is used to generate input patterns to build the classification model and the test dataset was used to evaluate its accuracy. 2.7. data mining techniques the techniques used in this research are all from the decision tree family. the output of these techniques is a set of rules extracted from the dataset of trauma patients. in the structure of the decision tree, by moving deeply from the root node to the leaf node, the assumptions of the rules were extracted. the techniques that were used include random forest, chaid, and id3. the random forest technique is also one of the techniques applied in the field of data mining. the random forest technique is often more accurate than a single classifier. this technique can manage data without preprocessing, and the need for data reduction and transformation. it operates by constructing a multitude of decision trees at training time . for classification tasks, the output of the random forest is the class selected by most trees. chaid is a decision tree-based method, in which the data space is divided into similar subsets in different iterations. this algorithm uses the chi-2 test to decide on each partition for partitioning. chaid analysis builds a predictive model, or tree, to help determine how variables best merge to explain the outcome in the given dependent variable. 3. results 3.1. baseline characteristics of patients twenty-three attributes were considered predictors. table 1 shows attributes, values, and numbers. the number of adults was 4 times the number of children, and iss for the majority of people who were brought to the emergency department (ed) or icu was considered as minor. also, the number of people with normal and abnormal vital signs was almost equal. the attribute of the time interval between the occurrence of injury and reaching the emergency department (minutes) had a large number of missing values. among the people whose information was registered, 2732 people had reached the emergency department in less than 10 minutes. with regard to the cause of trauma, road traffic accidents were the most common reason. 3.2. fidings of data mining techniques as shown in table 2, in terms of accuracy, random forest performs better than the other two techniques. the id3 technique performs better than the other two techniques in terms of the dead class. the random forest technique has performed better than other techniques in the living class. table 3 shows rules derived from applying different data mining techniques to the data set. the confidence (10) column means that the confidence is computed based on a 10minute threshold for patient arrival. moreover, the confidence (15) column means that the confidence is computed based on a 15-minute threshold for patient arrival. the rules are arranged in descending order, based on the amount of support. as shown in table 3, the rule with the most support, states that if iss is minor and vital signs are normal, the patient will survive with 98% confidence. the second rule, in terms of support, states that if iss is minor and vital signs are abnormal, the patient will survive with 93% confidence. also, by increasing the threshold of the patient’s arrival time from 10 to 15 minutes, no noticeable difference was observed in the death rate of patients. we had just three changes in the confidence level, and in some cases, the confidence level rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. nasr isfahani et al. 4 table 1: attributes, values, and numbers extracted from trauma registry attributes value (number) age children (2558) adolescents (2326) adults (21054) injury severity score (iss) minor (21300) moderate (4342) severe (209) very severe (134) vital signs normal (13093) abnormal (12891) time interval between the occurrence of the injury and arrival at the emergency department (minutes) <10 minutes (2372) 10-20 minutes (99) 20-30 minutes (34) 30-60 minutes (28) >60 minutes (41) history of hospitalization due to trauma yes (4434) no (21434) initial diagnosis of damage amputation (59) fracture (8734) tearing (662) trauma (94) foreign body (101) dislocation (206) laceration (924) cause of trauma non-penetrating traumas (building collapse, crush injuries,...) (2176), electrical injuries (26), animal attack (bites, paws, horns, etc.) (93), road traffic accidents (10251), suffocation (any type of respiratory arrest) (7), direct burn (cigarette, fire, flame) (75), fall (8789), sharp force trauma (cut, ...) (3682), blast injuries (16), animal bites (4), indirect burns (contact with heat, boiling water) (117), poisoning (inhalation, drugs, etc.) (44), drowning and submersion (5), unknown factors (14) ), other transport accidents (non-road accidents: train, plane, ship) (201), and other (310) number of admissions due to trauma once (3532) twice (632) three times (164) four times (57) five times (24) six times (7) approximate height of fall in meters less than or equal to one meter (6274) between one and two meters (1063) between two and three meters (614) between three and four meters (264) more than four meters (408) the position of the injured person cyclists (160), bus passengers (31), car passengers (1614), van passengers (57), heavy vehicle passengers (63), pedestrians (2220), and motorcyclists (2375) if the position of the person is non-pedestrian, choose the role of the injured person passenger (1414) driver (2682) type of incident collision (crash) (4256) rollover (1205) if the incident type is a collision, select the object type bicycle (16), van (3073), fixed object (283), pedestrian / animal (43), train (1), motorcycle (501), and heavy transport vehicle (188) if the injured person is a passenger of a car or motorcycle/bicycle, were appropriate safety devices used during the accident? yes (660) no (25324) if the injured person is a passenger (less than 8 years) in a car, were appropriate safety devices used during the accident? child seat? yes (2) no (25982) if the injured person is a passenger in a car, were appropriate safety devices used during the accident? airbag? yes (54) no (25930) if the injured person is a passenger on a motorcycle/bicycle, were appropriate safety devices used during the accident? helmet? yes (472) no (25512) transfer between centers (was the patient transferred to your facility by ambulance from another intensive care unit?) yes (4086) no (13189) glasgow coma scale (gcs) or early eye gcs (at the scene of the accident) does not open the eyes (52) opens the eyes in response to pain (67) opens the eyes in response to sound (177) the eyes are open spontaneously and without external stimulation (6935) glasgow coma scale (gcs) or early verbal gcs (at the scene of the accident) no sound is produced (43) incomprehensible sound (45) using inappropriate words (86) confused conversation (237) the victim is fully aware of time and place (6811) glasgow coma scale (gcs) or early motor gcs (at the scene of the accident) complete relaxation and immobility of the limbs (25) extends the limbs in response to pain (22) flexes the limbs in response to pain (55) withdraws from the painful stimulus (72) localization of the painful stimulus (183) obeys the examiner’s commands (6870) glasgow coma scale or initial total gcs (at the scene of the accident) mild brain injury (14h15) (6949) moderate brain injury (9h13) (158) severe brain injury (less than 9) (8) survival state survived (228) died (25757) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e1 table 2: sensitivity, precision and accuracy of data mining techniques methods sensitivity (95% ci) accuracy (95% ci) dead alive 96.53 (96.02 -97.04) 98.75 (98.3-99.2) 20.35 (18.2522.45) random forest 95.96 (95.56-96.36) 98.22 (97.67-98.77) 38.10 (36.30-39.90) id3 96.12 (95.74-96.5) 98.53 (98.02-99.04) 25.52 (23.52-27.52) chaid 99.53 (99.32-99.74) 99.75 (99.68-99.82) 15 (13.5-16.5) random forest + adaboost 99.16 (98.82-99.5) 99.51 (99.34-99.68) 28.57 (25.48-31.66) id3 + adaboost 99.26 (98.95-99.57) 99.97 (99.95-99.99) 7.14 (6.78-7.5) chaid + boosting data are presented with 95% confidence interval (ci). table 3: rules derived from applying different data mining techniques to the data set conditions co10 su10 co15 su15 if iss is minor and vital signs are normal 0.98 11352 0.98 11352 if iss is minor and vital signs are abnormal 0.93 9948 0.93 9948 if iss is minor, the person is an adult, and vital signs are normal 0.98 9078 0.98 9078 if iss is moderate and vital signs are normal 0.97 2686 0.97 2686 if iss is moderate and vital signs are abnormal 0.92 1656 0.92 1656 if iss is minor, the person is an adult, and vital signs are abnormal 0.93 8271 0.92 8271 if the person is an adult, the vital signs are normal, and the patient’s arrival time is ≤10 minutes 0.96 8246 0.94 8257 if iss is minor, the person is an adult, vital signs are abnormal, and the patient’s arrival time is ≤10 minutes 0.94 7407 0.91 7416 if iss is minor, the person is an adult, vital signs are normal, and the patient’s arrival time is ≤10 0.98 7164 0.97 7167 if iss is minor and the person is a child 0.99 3951 0.99 3951 if iss is minor, the person is an adult, the cause of the trauma is a road traffic accident, vital signs are abnormal, and the patient’s arrival time is ≤10 minutes. 0.97 3754 0.95 3785 if iss is moderate and the patient’s arrival time is less than or equal to 10 minutes 0.92 3462 0.92 3481 if the person is an adult, the cause of the trauma is a road traffic accident, the vital signs are normal, and the patient arrives in ≤10 minutes. 0.99 3146 0.98 3234 if iss is moderate, the person is an adult and vital signs are abnormal 0.92 2435 0.92 2435 if iss is minor, the person is an adult, vital signs are normal and arrival time is more than 10 minutes 0.99 1914 0.99 1987 if iss is minor, the person is an adult, the cause of the trauma is blunt force trauma (cut), vital signs are normal, and the patient’s arrival time is ≤10 minutes 0.99 1585 0.99 1615 if iss is moderate, the person is an adult, and vital signs are normal 0.94 1358 0.94 1358 if the person is a teenager, the cause of the trauma is a blow (cut), vital signs are abnormal, and the patient reaches ≤10 minutes 0.99 1094 0.98 1213 if the person is an adult, the cause of the trauma is non-penetrating injuries, the vital signs are normal, and the patient reaches the destination in ≤10 minutes 0.99 788 0.99 829 data are presented as survival rate and number of cases. rules with more than 90% confidence were introduced. co: confidence; su: support; co10 and co15: means that the confidence is computed based on a 10and 15-minute threshold for patient arrival; su10 and su15: means that the support is computed based on a 10and 15-minute threshold for patient arrival. iss: injury severity score. mained constant. the biggest change was related to the rule (if iss is minor, the person is an adult, vital signs are abnormal and the patient’s arrival time is less than or equal to 10 minutes, then the person will survive). in this rule, the confidence changed from 94 to 91 percent. 4. discussion in this study the data of 25,986 trauma patients were analyzed in an imbalanced dataset. the applied techniques were random forest, chaid, and id3. among the 132 attributes of the examined patients, 23 were selected as the most relethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. nasr isfahani et al. 6 vant. according to the results, random forest performed better than the other two techniques, in terms of accuracy. in this study, the accuracy and sensitivity of random forest were 96.53% and 98.75%, respectively. we investigated the condition of trauma patients throughout the country (iran). so far, no such study has been conducted in iran on this dataset using this number of records. also, in this study, rules were extracted that can help doctors in diagnosing the survival of trauma patients based on confidence and support criteria. by applying data mining techniques to the dataset, 21 rules were extracted. to check the obtained rules and select the most effective rules, confidence and support criteria were used. in general, rules should be selected whose confidence and support values are higher than the threshold set by the user (12). in this study, despite setting a threshold limit of 50% for confidence, rules with more than 90% confidence were introduced. also, according to the rules obtained in this study, the most effective attributes in the mortality of patients were extracted. these attributes included iss, being an adult or a child, vital signs, falls, and arrival time. these rules indicate the existence of a significant relationship between the iss and the patient’s survival, regardless of clinical symptoms and whether the patient is an adult or a child so that if the patient’s iss is classified as minor or moderate, the patient will survive with 94% certainty. in this regard, champion et al. showed that mortality and morbidity rates increase significantly with increase in triss (13). the relationship between iss and mortality in trauma patients has been investigated by several studies (14, 15). these studies indicate a relationship between injury severity and mortality in trauma patients, which is similar to the findings of the present study. age is also an important factor in the outcome of trauma patients, as mortality increases with age (16). also, these rules indicate the existence of a relationship between the time of the patient’s transfer to a hospital and his/her survival, regardless of vital signs. the rules also showed that in road accidents or the cases of penetrating and non-penetrating (blunt) injuries, if the patient’s time to reach the emergency department is less than 10 minutes, regardless of the vital signs, the patient will survive with 97% certainty. a study of the transfer time to the center for patients with acute traumatic subdural hemorrhage showed that those who arrived quickly from the site of injury to a designated trauma center were more likely to survive (17). various studies have shown that reducing the time between injury and definitive treatment improves outcome and is known as the "golden time" in trauma (18, 19). in one of the rules, it was also stated that if the cause of the trauma is a fall and the vital signs are abnormal, the person will survive with 98% certainty. another rule also showed that if the patient’s iss is minor, the vital signs are normal, and the person is an adult, even if the time to reach the emergency department is more than 10 minutes, the patient will survive with 99% certainty. these rules should be interpreted considering that the data of the registries used in this dataset were extracted from the most advanced trauma centers in iran, in which specialized services are provided by experienced specialists. for this reason, the cases leading to death in the field of falls and other areas of trauma are less common in these centers. meanwhile, it is necessary to note that these results cannot be generalized to all trauma patients, because a percentage of patients died at the scene and were not transferred to the emergency department at all, so their information is not available in the dataset. pre-hospital communication, transport system, trained personnel, and qualified trauma care personnel are all of great importance for the success of a trauma system (20). therefore, in general, it seems that in terms of human resources and diagnostic and treatment modalities, if patients are transferred to trauma centers as soon as possible, the probability of their survival would be very high. for this reason, pre-hospital emergency medical services (ems) needs to be carefully examined to adopt new technologies, techniques, and tools to improve these systems, if necessary, which may in turn lead to improved quality of care in trauma patients (21). pre-hospital trauma care has a direct impact on survival. this system should ensure rapid access and dispatch of qualified personnel, appropriate on-scene care, and safe and rapid transfer of the patient to the nearest and most appropriate facility. the primary focus is on training paramedics to provide basic resuscitation, triage, and treatment for trauma patients. effective pre-hospital care requires coordination between various public safety agencies and hospitals to maximize efficiency, minimize duplicate services, and provide care at a reasonable cost (20). it is also suggested to pay attention to the improvement of the trauma transportation system and transportation times for severe trauma patients. several studies have shown that increase in the transportation time of trauma patients leads to increased mortality (22). as a result, complications due to long transportation and insufficient resuscitation can be predicted and a higher level of care can be considered for these patients. also, since studies show that for severe trauma patients with iss >12, air transportation is more effective than ground transportation (23), it is better to pay more attention to air transportation for these patients and improve the care for the area of trauma. 5. limitation among the limitations of this research, we can mention the imbalance of the dataset, so that the number of data of deceased people is almost 2% of the dataset, and 98% of the data were related to survived patients. in order for a provincial center to be included in the national trauma registry of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e1 iran, a minimum requirement of human resources, equipment, and level of health care service are considered by the strategic council held annually. moreover, this paper used bootstrap sampling technique to avoid the imbalance as much as possible. 6. conclusion in road traffic accidents, if the iss is minor or moderate and the vital signs are normal, the person will survive with 98% certainty, and if the vital signs are abnormal, the person will survive with 92% certainty. if iss is minor in penetrating trauma, regardless of vital signs and if the patient is transported in less than ten minutes, the person will survive with 98% certainty. also, if the iss is minor in non-penetrating trauma, regardless of vital signs and if the patient is transported in less than ten minutes, the person will survive with 99% certainty. as a result, complications due to long transportation and insufficient resuscitation can be predicted and a higher level of care can be considered for these patients. if the patient is tagged as iss-minor, the vital signs are normal and the person is an adult, even if the time to reach the emergency department is more than 10 minutes, the patient will survive with 99% certainty. if the person is an adult, has non-penetrating (blunt) injuries, the vital signs are normal, and the patient reaches the destination in less than or equal to 10 minutes, the person will survive with 99% certainty. 7. declarations 7.1. acknowledgments we thank national trauma registry of iran, affiliated with, sina trauma and surgery research center, and isfahan trauma registration center. we also appreciate the information and advice shared by professor peyman salamati. 7.2. author contributions the authors confirm contribution to the paper as follows: study conception and design: m.s, m.n.i; data collection: n.a.f, m.n.i; analysis and interpretation of results: m.s, m.n.i., h.b, n.t; draft manuscript preparation: m.s. all authors reviewed the results and approved the final version of the manuscript. 7.3. ethical permission this article does not contain any studies with human participants or animals. ethical code: ir.mui.nurema.rec.1400.044 7.4. informed consent not applicable. 7.5. conflicting interests authors declare that they have no conflict of interest 7.6. funding the research was funded by vice chancellery for research at isfahan university of 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technology( jact). 2018;12(2):119-26. 6. amin ms, chiam yk, varathan kd. identification of significant features and data mining techniques in predicting heart disease. telematics and informatics(ti). 2019;36:82-93. 7. yadollahi m. a study of mortality risk factors among trauma referrals to trauma center, shiraz, iran, 2017. chinese journal of traumatology(cjt). 2019;22(04):212-8. 8. hassanzadeh m fays. using data mining techniques to extract clinical disorders affecting mortality in trauma patients. guilan uni med sci(gums). 2015;24(95):62-52. 9. liu nt, salinas j. machine learning for predicting outcomes in trauma. shock: injury, inflammation, and sepsis: laboratory and clinical approaches(lca). 2017;48(5):504-10. 10. rau c-s, kuo p-j, chien p-c, huang c-y, hsieh hy, hsieh c-h. mortality prediction in patients with isolated moderate and severe traumatic brain injury using machine learning models. plos one(pso). 2018;13(11):e0207192. 11. gonzález-robledo j, martín-gonzález f, moreno-garcía m, sánchez-barba m, sánchez-hernández f. prognostic factors associated with mortality in patients with severe trauma: from prehospital care to the intenthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. nasr isfahani et al. 8 sive care unit. medicina intensiva(mi) (english edition). 2015;39(7):412-21. 12. arora j, bhalla n, rao s. a review on association rule mining algorithms. international journal of innovative research in computer and communication engineering(ijircce). 2013;1(5):1246-51. 13. champion hr, copes ws, sacco wj, lawnick mm, keast sl, frey cf. the major trauma outcome study: establishing national norms for trauma care. journal of trauma and acute care surgery( jtacs(. 1990;30(11):1356-65. 14. kuo sch, kuo p-j, chen y-c, chien p-c, hsieh h-y, hsieh c-h. comparison of the new exponential injury severity score with the injury severity score and the new injury severity score in trauma patients: a cross-sectional study. plos one(pso). 2017;12(11):e0187871. 15. lovely r, trecartin a, ologun g, johnston a, svintozelskiy s, vermeylen f, et al. injury severity score alone predicts mortality when compared to ems scene time and transport time for motor vehicle trauma patients who arrive alive to hospital. traffic injury prevention(tip). 2018;19(sup2):s167-s8. 16. chong s-l, liu n, barbier s, ong meh. predictive modeling in pediatric traumatic brain injury using machine learning. bmc medical research methodology(bmrm). 2015;15(1):1-9. 17. tien hcn, jung v, pinto r, mainprize t, scales dc, rizoli sb. reducing time-to-treatment decreases mortality of trauma patients with acute subdural hematoma. annals of surgery(as). 2011;253(6):1178-83. 18. mcnicholl bp. the golden hour and prehospital trauma care. injury. 1994;25(4):251-4. 19. murdock db. trauma: when there’s no time to count. association of perioperative registered nurses journal(aornj. 2008;87(2):322-8. 20. hoyt db, coimbra r, potenza bm. trauma systems, triage, and transport. trauma. 2008;6:57-82. 21. williamson k, ramesh r, grabinsky a. advances in prehospital trauma care. international journal of critical illness and injury science(ijciis(. 2011;1(1):44. 22. feero s, hedges jr, simmons e, irwin l. does out-ofhospital ems time affect trauma survival? the american journal of emergency medicine(ajem). 1995;13(2):133-5. 23. mitchell ad, tallon jm, sealy b. air versus ground transport of major trauma patients to a tertiary trauma centre: a province-wide comparison using triss analysis. canadian journal of surgery(cjs). 2007;50(2):129. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e18 ca s e re p o rt posterior lingual abscess; report of two cases miguel saro-buendía1,5∗, pedro suarez urquiza2, judit amigo gonzález3, maria josé lesmas navarro1, miguel mazón4, miguel armengot carceller1,5 1. department of otorhinolaryngology, la fe university and polytechnic hospital, valencia, spain. 2. department of microbiology, la fe university and polytechnic hospital, valencia, spain. 3. department of internal medicine, la fe university and polytechnic hospital, valencia, spain. 4. department of radiology, la fe university and polytechnic hospital, valencia, spain. 5. department of surgery, faculty of medicine, university of valencia, spain. received: october 2022; accepted: december 2022; published online: 14 january 2023 abstract: the lingual abscess is rare due to several protective mechanisms against infection in this location. concretely, the abscess in the base of the tongue (posterior lingual abscess) is even more exceptional. its prompt detection is crucial to avoid potentially fatal airway complications. to familiarize physicians with this condition, we report 2 cases of posterior lingual abscess. both were referred to our emergency department due to minor oropharyngeal complaints. finally, both were diagnosed and required surgical drainage. the clinical evolution was successful: both were discharged in less than 72 hours and follow-up one week later confirmed clinical recovery. keywords: abscess; tongue; airway management; emergency medicine cite this article as: sarobuendía m, suárez urquiza p, amigo gonzález j, lesmas navarro mj, mazón m, armengot carceller m. posterior lingual abscess; report of two cases. arch acad emerg med. 2023; 11(1): e18. https://doi.org/10.22037/aaem.v11i1.1860. 1. introduction the tongue is the most voluminous oral cavity structure and is a common disease site (1). however, abscesses in this location are rare due to several protective mechanisms against infection and knowledge about the condition is limited (2, 3). the lingual abscess might be anterior (ala; affects the anterior two thirds of the tongue or oral tongue) or posterior (pla; affects the posterior third of the tongue or tongue base). the differentiation is relevant, the pla is less frequent, its diagnosis is more challenging and implies a greater risk of airway compromise. also, the underlying causes and management differ (3, 4). the ala is traditionally caused by bite trauma or seizure and is evident on examination (5). the pla underlying causes might be lingual tonsillitis, infected thyroglossal duct cyst remnants, penetration of foreign objects, or extension from a dental infection (4). due to its rarity, little is known about epidemiological features of p-la (4, 5). here we report two cases of p-la, the objective is to enhance suspicion about this entity as a potentially fatal condi∗corresponding author: miguel sarobuendía; fernando abril martorell avenue, 106, postal code 46026. email: msarobuendia@gmail.com, phone: +34671 688 648, orcid: https://orcid.org/0000-0003-4794-3615. tion behind minor oropharyngeal complaints and findings. 2. case presentation 2.1. case 1 a previously healthy 26-year-old woman presented to our emergency department (ed) with odynophagia and oropharyngeal erythema on examination. she received an acute pharyngitis diagnosis. she was readmitted to the ed 24 hours later due to symptomatic worsening (fever, increased muffled voice, and halitosis). flexible endoscopy showed a left side tongue base tumefaction (figure 1). lab tests showed leucocytosis with left-deviation and raised c reactive protein levels of 92.8 mg/ l. contrast-enhanced neck computed tomography (ct) scan showed a left side tongue base abscess (figure 2). a p-la was diagnosed, and the patient was hospitalized for close clinical observation and intravenous therapy with broad-spectrum antibiotics (combination of ceftriaxone and clindamycin) and anti-inflammatory drugs (methylprednisolone, dexketoprofen). after 10 hours, due to the lack of clinical improvement, surgical drainage was required. the surgical technique consisted of a tongue base exploration with a glidescope® laryngoscope. then, a wide incision with cold instruments over the tumefaction was performed to drain the abscess. samples of purulent fluid revealed a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. saro-buendía et al. 2 figure 1: endoscopic visualization of tongue base at the emergency department before surgery and 1 week after surgery (at follow-up). case 1: left tongue base tumefaction obliterates the ipsilateral vallecula and contacts the epiglottis. case 2: left wellcircumscribed vallecula tumefaction contacting the epiglottis. normal tongue base findings are seen after surgery in the two cases. mixed infection including streptococcus spp. and fusobacterium spp. the patient showed clinical improvement and was discharged in 72 hours. she completed the treatment at home. at the follow-up visit one week later, she presented full clinical and endoscopic recovery (figure 1). 2.2. case 2 a previously healthy 47-year-old woman presented to the ed with a 72-hour history of odynophagia, muffled voice, and asthenia. direct visualization showed mild oropharynx erythema. flexible endoscopy showed a left well-circumscribed vallecula tumefaction (figure 1). lab tests showed leucocytosis with left-deviation and raised c reactive protein levels of 30.4 mg/l. contrast-enhanced neck ct scan showed a left side vallecula-tongue base abscess (figure 2). a p-la was diagnosed and the patient was hospitalized for close clinical observation and intravenous therapy (same as case 1). after 18 hours, due to the lack of improvement, surgical drainage was indicated. the surgical technique consisted of the p-la exposure with a kleinsasser laryngoscope and a wide incision with cold instruments to drain the abscess. culture of the purulent fluid revealed mixed flora. the patient showed clinical improvement and was discharged in 48 hours to complete the treatment at home. at the follow-up visit one week later, the patient presented full clinical and endoscopic recovery (figure 1). 3. discussion the prompt detection of a p-la is crucial and a diagnostic delay can result in sepsis, mediastinitis, and a fatal airway obthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e18 figure 2: contrast-enhanced neck computed tomography scan. left (case 1): left tongue base focal fluid collection of low attenuation with surrounding rim-enhancement and pre-epiglottic fat stranding. right (case 2): left vallecula-tongue base focal fluid collection of low attenuation with surrounding rim-enhancement. struction (5-8). diagnosis can be challenging because the p-la clinical presentation is usually vague and unspecific and, as happened with case 1, might lead to the misdiagnosis (6, 7). orolingual palpation helps to detect a p-la (5). however, we did not perform palpation and we believe this manoeuvre is not routinely required in patients referring with mild odynophagia. the posterior third of the tongue is visualized by direct or indirect laryngoscopy techniques (6). lab tests show normal levels of white blood cells or slight leucocytosis like in our cases (4, 5, 8). common pathogens are those corresponding to normal flora of oral cavity and oropharynx (4, 5). our samples presented streptococcus spp. and fusobacterium spp. imaging provides the key to confirm the p-la diagnosis and evaluate its extension (4, 5). contrast-enhanced ct scan might show the abscess as a low attenuation focal confined collection with capsular rimenhancement (figures 2) and might identify the underlying cause. however, in our cases the underlying cause was not identified. regarding management, three domains must be contemplated. first, maintaining the airway patency is crucial (6, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. saro-buendía et al. 4 8). there should be a low threshold for awake intubation and tracheostomy might be needed (8). second, the abscess must be drained, an exception to this rule can be sub centimetre collections, which might respond to isolated medical therapy (7). third, empirical broad-spectrum antibiotics should be administered to cover both aerobic and anaerobic bacteria arising in the oral cavity and oropharynx (5, 8, 9). the abscess drain can be performed using needle aspiration or, as we did, using transoral surgery (2, 4, 9). needle aspiration has advantages like the possibility to avoid general anaesthesia and endotracheal intubation (2, 9). however, transoral surgery may be the best option to assure a successful drainage and prevent reinfection (10). in our cases surgery was successful with no complications and, within a week, both patients presented a full clinical and endoscopic recovery. 4. conclusions the posterior lingual abscess is rare. however, it is relevant for physicians, because its prompt diagnosis and management should minimize the risk of potentially fatal airway complications. 5. declarations 5.1. acknowledgments none. 5.2. competing interests none. 5.3. funding source none. 5.4. authors contribution miguel sarobuendía: main contributor, study conception and design, acquisition and interpretation of data, draft of manuscript and preparation, final version approval. pedro suarez urquiza and judit amigo gonzález: study design, acquisition and interpretation of data, draft of manuscript and preparation, final version approval. maria josé lesmas navarro: data acquisition, interpretation of data, final version approval. miguel mazón: participated in the artworks and selection of figures. grammar review, final version approval. miguel armengot carceller: study conception and design, interpretation of data, final version approval. 5.5. patient consent statement both patients participated voluntarily and consented to the publication of clinical information related to their cases. the study follows the principles outlined in the declaration of helsinki and is in accordance with the ethics committee of our institution (code 2022-756-1). 5.6. sponsorships none. references 1. byrd ja. ba, rogers iii rs. . glossitis and other tongue disorders. dermatol. clin. 2003;21(1):123-34. 2. balatsouras dg., eliopoulos pn., kaberos ac. lingual abscess: diagnosis and treatment. head neck. 2004;26(6):550-4. 3. antoniades k, hadjipetrou l, antoniades v, antoniades d. acute tongue abscess. report of three cases. oral surg oral med oral pathol oral radiol endod. 2004;97(5):5703. 4. vellin jf, crestani s, saroul n, bivahagumye l, gabrillargues j, gilain l. acute abscess of the base of the tongue: a rare but important emergency. j emerg med. 2011;41(5):e107-10. 5. sands m. pj, & brown r.b. . tongue abscess: case report and review. clin. infect. dis. 1993;16(1):133-5. 6. schweigert j, christian r, kemp wl. challenges in the diagnosis of a posterior lingual abscess, a potential lethal disorder: a case report and review of the literature. am j forensic med pathol. 2020;41(1):64-6. 7. awai s, miller bj, dimitrov l, williamson aj. lingual tonsil abscess: a rare, life-threatening cause of acute sore throat. bmj case rep. 2019;12(5):e229555. 8. srivanitchapoom c, yata k. lingual abscess: predisposing factors, pathophysiology, clinical manifestations, diagnosis, and management. int j otolaryngol. 2018;2018:4504270. 9. barrueco ás. dm, huerta ij., juncos jmm., & álvarez ca. recurrent lingual abscess. acta otorrinolaringol. esp. 2012;63(4):318-20. 10. harrington at, hsia jc, mendez e, clarridge je. a lingual abscess caused by streptococcus intermedius. j med microbiol. 2012;61(pt 4):590-2. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction case presentation discussion conclusions declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 1 emergency (2015); 3 (1): 1 letter to editor description of a working day as a senior emergency medicine resident; burning candle at both ends! alireza baratloo, marzieh maleki* department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran *corresponding author: marzieh maleki; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. postal code: 1989934148; tel: +989123088257; fax: +982122721155; e-mail: marziehmaleki@yahoo.com received: 13 oct 2014; accepted: 5 nov 2014 to the editor: his text is a real-time description of an emergency medicine resident’s shift in an overcrowded emergency department (ed), tehran, iran. it is 3:35 pm of a warm afternoon; the emergency department is filled up with ill patients. carrying in hand the file of a patient who had three episodes of convulsive seizure, you have to writing an order for another patient with suspected pulmonary embolism. simultaneously, you are confronting with a pregnant woman complaining from loss of her baby’s movements and an addicted case with hangover feeling and low blood pressure. in addition, you have to provide a bed for the patient who is complaining from typical angina pectoris from the last night. when you decide to give the orders of the first patient to the nursing service, an intern informs you that another patient with st segment elevation myocardial infarction has been presented. meanwhile, the mother of the addicted patient requests you to attend to her boy. as you visit him, you find out his condition worsen than you thought; he is burning with fever accompanying with prominent respiratory distress and tachycardia. while you are completely being exhausted and stressed due to the work pressures, you have to control your anger to do not tearing the disastrous history sheet taken by the intern. as you ask the intern to rewrite the history, another patient presents with decompensated cardiac heart failure. when you leave the last patient, notice that no one has yet applied venipuncture to the addicted case because of fear from his positive history of acquired immune deficiency syndrome (aids). at this time, you are called for joining to grand round of ward’s patients by corresponding emergency medicine attending physician. you eventually feel the world are collapsing on your head. after about 12 hours uninterrupted presence in the ed, hand over the shift with lots of patients with unknown diagnoses and partial treatments. you may just satisfy because of the addict’s mother deeply praying for you! what is your judgment? in such aforementioned situation, is medical errors, delay in service presentation, and patients’ dissatisfaction avoidable? today, overcrowding in eds has turned out to be one of the most important problems in health systems around the world. the short and accessible solution in this regard could not be reached easily. in fact, several basic reasons play a role in such a problem and eliminating each of them would require a long-term planning. this issue not only has a negative effect on the quality of services, but also produces both psychological and physical effects on the ed staff. in addition, it also causes increased dissatisfaction among referees as well as excessive exhaustion among staffs (1, 2). an increase in the number of unnecessary referees in non-emergency cases is one of the major factors for overcrowding. another recognized factor responsible for overcrowding in emergencies is the lack of timely disposition. requesting the unnecessary paraclinical procedures and unrelated consultations are other defendants. lack of difference in the calculation of costs between emergent and non-emergent cases are considered as some of influencing factors that increase the expectation level of referees and overcrowding in state emergency centers (3, 4). references: 1. olshaker js. managing emergency department overcrowding. emerg med clin north am. 2009;27(4):593603. 2. baker we. evaluation of physician competency and clinical performance in emergency medicine. emerg med clin north am. 2009;27(4):615-26. 3. hashemi b, baratloo a, rahmati f, et al. emergency department performance indexes before and after establishment of emergency medicine. emergency. 2013;1(1): 20-3. 4. yu kt, green ra. critical aspects of emergency department documentation and communication. emerg med clin north am. 2009;27(4):641-54. t archives of academic emergency medicine. 2023; 11(1): e49 rev i ew art i c l e point-of-care ultrasonography for identification of skin and soft tissue abscess in adult and pediatric patients; a systematic review and meta-analysis erfan rahmani1, ehsan fayyazishishavan2, arian afzalian1, sanaz varshochi1, reza amani-beni3, seyed-amirabbas ahadiat4, zeynab moshtaghi5, seyyed-ghavam shafagh6, roya khorram7, elnaz asadollahzade8, raihaneh atbaei9, mohammad saeed kahrizi10, atoosa rahbari11, negar baharlouie3, farzaneh mostanbet12, bahamin amirabadiquchani13, moein kiani14, mozhdeh memarizadeh12, shahin keshtkar rajabi15, reza barati6, hengame hajinouri16, shahrzad najafi1, zeynab abdollahi17, nahid dadashzadehasl18, atousa moghadam fard26, mozhgan afshar19, atefeh abedi20, sara saeidi21, adeleh mansourirad22, pedram emami shahrezaei23, sepideh shah hosseini6, zahra rostami ghotbabadi12, reza vafadar24, roozbeh roohinezhad6, nogol ghalamkarpour25, mehrdad farrokhi26∗ 1. graduated, school of medicine, tehran university of medical sciences, tehran, iran. 2. department of biostatistics and data science, school of public health, the university of texas health science center at houston (uthealth), houston, tx 77030, usa. 3. school of medicine, isfahan university of medical sciences, isfahan, iran. 4. girona university, girona, spain. 5. graduated, faculty of nursing, bushehr university of medical sciences, bushehr, iran. 6. school of medicine, iran university of medical sciences, tehran, iran. 7. bone and joint diseases research center, department of orthopedic surgery, shiraz university of medical sciences, shiraz, iran. 8. multiple sclerosis research center, neuroscience institute, tehran university of medical sciences, tehran, iran. 9. school of medicine, jahrom university of medical sciences, jahrom, iran. 10.school of medicine, alborz university of medical sciences, karaj, iran. 11.islamic university of azad medical branch, tehran, iran. 12.school of medicine, shiraz university of medical sciences, shiraz, iran. 13.mashhad university of medical sciences, mashhad, iran. 14.school of medicine, zanjan university of medical sciences, zanjan, iran. 15.firoozabadi hospital clinical research development unit (fhcrdu), department of internal medicine, school of medicine, iran university of medical sciences (iums), tehran, iran. 16.school of medicine, islamic azad university, tehran, iran. 17.department of radiology, school of medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran. 18.legal medicine research center, iranian legal medicine organization, tehran, iran. 19.university of psychology sciences, south azad tehran, iran. 20.dental and periodontal research center, tabriz university of medical sciences, tabriz, iran. 21.students research committee, faculty of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran. 22.herman ostrow school of dentistry, university of southern california, los angeles, california, usa. 23.islamic azad university of najafabad, najafabad, iran. 24.department of orthopedic surgery, kerman university of medical sciences, kerman, iran. 25.department of clinical laboratory sciences, school of allied medicine, student research committee, lorestan university of medical sciences, khorramabad, iran. 26.eris research institute, tehran, iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 2 received: may 2023; accepted: june 2023; published online: 16 july 2023 abstract: introduction: differentiating the soft tissue abscess from other types of skin and soft tissue infections (sstis) poses a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. this meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments. methods: a comprehensive literature search of medline, scopus, web of science, embase, and google scholar, from inception to january 2023, was conducted to identify relevant studies investigating the diagnostic performance of point-of-care ultrasonography for identification of abscess. methodological quality of the included studies was assessed using a revised tool for the quality assessment of diagnostic accuracy studies (quadas-2). results: the pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% ci: 0.92–0.94); specificity, 0.87 (95% ci: 0.85–0.89), and the area under the summary receiver-operating characteristic (sroc), 0.95. the pooled sensitivity, specificity, and area under the sroc of studies in adult patients were 0.98 (95% ci: 0.92–1), 0.92 (95% ci: 0.86–0.95), and 0.99, respectively. the pooled sensitivity, specificity, and area under the sroc of studies in pediatric patients were 0.9 (95% ci: 0.87–0.92), 0.78 (95% ci: 0.73–0.82), and 0.91, respectively. conclusion: our meta-analysis demonstrated that the point-of-care ultrasonography has excellent diagnostic value for the abscess in the emergency department. furthermore, we found that the diagnostic performance of point-of-care ultrasonography for diagnosis of abscess was higher for adult cases than for pediatric patients. keywords: abscess; cellulitis; diagnostic imaging; meta-analysis; ultrasonography cite this article as: rahmani e, fayyazishishavan e, afzalian a, varshochi s, amani-beni r, et al. point-of-care ultrasonography for identification of skin and soft tissue abscess in adult and pediatric patients; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e49. https://doi.org/10.22037/aaem.v11i1.2021. 1. introduction skin and soft tissue infections (sstis) are a highly prevalent presenting complaint in the ambulatory setting and also emergency department (1, 2). recent investigations have shown that although the rise of methicillin-resistant staphylococcus aureus can lead to significant increase in admission rates, duration of hospitalizations, and ambulatory and emergency department visits, most patients with suspected abscess are treated in emergency departments using incision and drainage as the gold standard of care (3, 4). differentiating the soft tissue abscess from other types of sstis pose a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. indeed, cases with abscess are managed using drainage, whereas patients with cellulitis are commonly treated using systematic antibiotics (1). this misclassification can lead to unnecessary invasive interventions, exposure to sedation-related adverse events, and inappropriate management in patients with cellulitis (5). it has been shown that point-of-care ultrasonography as an adjunct to physical evaluations can improve the accuracy of diagnosis of skin abscess in cases with sstis and result in change in the decision to perform incision and drainage (6). a number of studies have in fact shown that point-of-care ultra∗corresponding author: mehrdad farrokhi; eris research institute, tehran, iran. email: dr.mehrdad.farrokhi@gmail.com, phone number: +989384226664, orcid: https://orcid.org/0000-0002-1559-2323. sonography is superior to physical evaluation alone for diagnosis of abscess, but there is limited evidence supporting its efficacy in the emergency departments (7-9). furthermore, conflicting findings have been reported in the literature regarding the accuracy of point-of-care ultrasonography for evaluation of sstis in the emergency departments (10, 11). in addition, previous investigations of point-of-care ultrasonography for diagnosis of abscess in pediatrics showed less consistency in comparison with data from investigations in adults, emphasizing the importance of further diagnostic studies (8, 11-13). although majority of previous studies suggest the point-of-care ultrasonography for evaluation of sstis in the emergency department, systematic reviews and meta-analyses are required to determine the exact diagnostic accuracy of this imaging modality. therefore, this systematic review and meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments and also the subgroup of pediatric patients. 2. methods 2.1. search strategy this systematic review and meta-analysis of diagnostic studies was carried out according to the preferred reporting items for systematic reviews and meta-analyses for diagnostic test accuracy (prisma-dta) guidelines. a comprehensive literature search of medline, scopus, web of science, embase, and google scholar, from inception to january 2023, was conducted to identify relevant studies investigating the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e49 diagnostic performance of point-of-care ultrasonography for diagnosis of abscess. our searches were limited to peerreviewed published papers and abstracts in english. moreover, the references of the relevant papers were manually screened for the potential studies. the systematic search was performed using medical subject heading (mesh) terms, keywords, and boolean operators: “ultrasound” or “ultrasonography” or “sonography” or “sono” or “ultrasonic” or “sonogram” and “skin and soft tissue infections” or “ssti” or “sstis” or “soft tissue infections” or “skin diseases, infectious” or “staphylococcal skin infections” or “soft tissue injuries” or “suppuration” or “suppurate” or “pus” or “abscess” or “cellulitis” or “gram positive infection” or “bacterial infection”. 2.2. study selection and eligibility criteria results from the electronic database search were assessed by two independent authors (mf and rab) based on the keywords included in title and abstract for relevance and evaluated for inclusion criteria based on full text. since screening process was managed using endnote software, any duplicate studies were initially removed from the results. any discrepancies and disagreements regarding studies evaluated for possible eligibility based on title and abstract or inclusion based on full text were resolved by discussion and consultation with a third author. the papers were included in the study if they evaluated the diagnostic accuracy of pointof-care ultrasonography for diagnosis of abscess, reported a 2 × 2 table containing true positive (tp), false positive (fp), true negative (tn), and false negative (fn), reported an original study or a case series with more than 10 cases, and published in english. we excluded systematic reviews and metaanalyses, case reports, case series with less than 10 patients, editorials, studies without extractable data to provide a 2 × 2 table, and papers published in languages other than english. 2.3. data extraction two independent authors (am and mf) extracted data from each included study using a standardized data extraction sheet. data extracted from each study included first author, publication year, sample size, country, study location, mean age, sex, study design, prevalence of abscess, study population, diagnostic performance of point-of-care ultrasonography (tp, tn, fp, fn, sensitivity, and specificity), and gold standard. any disagreements throughout data extraction were resolved through discussion with a third author. 2.4. methodological quality assessment two independent authors (mf and rab) separately assessed the methodological quality of the included studies using a revised tool for the quality assessment of diagnostic accuracy studies (quadas-2) tool. any discrepancies about the results of this tool were resolved through consultation with a third author. 2.5. statistical analysis statistical analysis was conducted using meta-disc software version 1.4 (ramona cajal hospital, madrid, spain) and stata statistical software package (stata corp., college station, tx, usa) (version 17.0). we used cochrane q-test and i2 to evaluate the heterogeneity among the included studies. a p-value less than 0.05 for q-test or i2 higher than 50% indicate a significant heterogeneity among the included studies and a random-effects model was used. on the other hand, if pvalue of q-test was higher than 0.05 and i2 was less than 50%, a fixed-effects model was used for estimation of diagnostic parameters. publication bias was investigated using funnel plot and begg’s test. we calculated spearman’s rank correlation coefficient to assess the threshold effects. 3. results 3.1. search results initial search of the electronic databases yielded a total of 2564 studies, after which 917 duplicate papers were excluded. from the 1647 nonduplicate studies, 1602 studies were excluded after title and abstract screening. fortyfive studies were chosen for full-text evaluation. afterwards, 30 studies were excluded due to having poor quality, nonextractable data, and being irrelevant. as a result, 15 studies met all eligibility criteria and were included in this metaanalysis. figure 1 shows the prisma flowchart of inclusion and exclusion of the studies. 3.2. characteristics of the included studies the included studies encompassed 2615 patients, ranging from a minimum of 23 to a maximum of 1216. these studies were published between 1997 and 2020. thirteen of the included studies were performed in usa, one in ireland, and one in lebanon. the reported mean age and the percentage of females ranged from 1.95 to 42 years and 31% to 64%, respectively. fourteen studies had prospective observational design and one study was a clinical trial. table 1 summarizes the main characteristics of the 15 included studies. 3.3. methodological quality of the included studies table 2 presents our evaluation of the risk of bias and applicability domains of the 15 included studies in this metaanalysis using quadas-2 tool. overall, the majority of the studies were considered to have low risk of bias and applicability concerns. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 4 3.4. screening performance characteristics of ultrasonography spearman’s correlation coefficient for ultrasonography was 0.11 with a p value of 0.7, demonstrating that there is no threshold effect. there was a significant betweenstudy heterogeneity for sensitivity (i2=74.4% and p<0.01), specificity (i2=81% and p<0.01), positive likelihood ratio (plr) (i2=83.8% and p<0.01), negative likelihood ratio (nlr) (i2=79% and p<0.01), and diagnostic odds ratio (dor) (i2=80.6% and p<0.01). the pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% ci: 0.92–0.94); specificity, 0.87 (95% ci: 0.85–0.89); positive likelihood ratio, 6.23 (95% ci: 3.91–9.92); negative likelihood ratio, 0.09 (95% ci: 0.05–0.15); and diagnostic odds ratio, 95.66 (95% ci: 40.46–226.18) (figures 2-6). the area under the sroc curve for the accuracy of ultrasonography to diagnose abscess in the emergency settings was 0.95 (fig. 7). 3.5. subgroup analysis the pooled sensitivity, specificity, plr, nlr, and area under sroc of studies (n=4) in adult patients were 0.98 (95% ci: 0.92–1), 0.92 (95% ci: 0.86–0.95), 9.02 (95% ci: 4.3118.87), 0.03 (95% ci: 0.01-0.08), and 0.99, respectively. the pooled sensitivity, specificity, plr, nlr, and area under sroc of studies (n=7) in pediatric patients were 0.9 (95% ci: 0.87–0.92), 0.78 (95% ci: 0.73–0.82), 4.08 (95% ci: 3.11-5.37), 0.14 (95% ci: 0.08-0.25), and 0.91, respectively. 3.6. publication bias results of begg’s test (p=0.58) and egger’s test (p=0.30) revealed that there was no significant publication bias in the included studies. similarly, the funnel plot of the studies showed no significant publication bias (fig. 8). 4. discussion in this systematic review and meta-analysis, we investigated the diagnostic accuracy of point-of-care ultrasonography for diagnosis of abscess in the emergency department and also the subgroups of pediatric and adult patients. the overall sensitivity, specificity, and accuracy of point-of-care ultrasonography for diagnosis of abscess were 0.93, 0.87, and 0.96, respectively. the sensitivity, specificity, and accuracy of point-of-care ultrasonography for diagnosis of abscess in adult patients were 0.98, 0.92, and 0.99, respectively. the meta-analysis of studies on pediatric cases found that the pooled sensitivity, specificity, and accuracy of point-of-care ultrasonography for diagnosis of abscess are 0.9, 0.78, and 0.91, respectively. these findings show that overall diagnostic performance of point-of-care ultrasonography for diagnosis of abscess is acceptable. however, the pooled estimates of diagnostic parameters revealed that sensitivity, specificity, and accuracy of point-of-care ultrasonography for diagnosis of abscess in pediatric patients is lower than those of adult cases. this may in part be clarified by differences between adult and pediatric cases with respect to the body habitus, as larger body sizes of adult patients may increase accuracy of point-of-care ultrasonography for detection of drainable abscesses. moreover, final diagnosis of abscess is confirmed by incision and drainage and this procedure may require not only pain control, but also conscious sedation. consequently, collaboration of the patients or their parents for further evaluations can be affected, which may reduce the accuracy of point-of-care ultrasonography for diagnosis of abscess. in a randomized clinical trial by gaspari et al. (14), 125 cases presenting to emergency department with soft tissue abscess were randomized to incision and drainage with physical examination or incision and drainage with point-of-care ultrasonography. the main assessed outcome in this study was failure of treatment at 10 days. the results of this study showed that point-of-care ultrasonography in addition to diagnosis of abscess, can reduce the rate of failure or need for repeated incision and drainage in patients with soft tissue abscess. however, since the vast majority of the included studies in our meta-analysis did not investigate the effect of point-of-care ultrasonography on the rate of treatment failure, we were not able to predict the pooled value of this outcome. in a similar systematic review and meta-analysis by subramaniam et al. (15), several electronic databases including embase, web of science, cinahl, cochran, and medline were systematically searched from inception to 2015 to find studies evaluating the diagnostic performance of point-ofcare ultrasonography for identification of abscess in emergency departments. they included four studies on adult patients and two studies on pediatric patients with a total number of 800 cases. they reported that sensitivity and specificity of point-of-care ultrasonography for diagnosis of abscess were 0.97 and 0.83, respectively. these parameters were higher than those calculated in our meta-analysis. one possible explanation for this inconsistency could be the difference between our meta-analysis and their study with respect to the number of included studies and the total number of assessed cases. moreover, since they only reported the overall sensitivity and specificity of point-of-care ultrasonography for diagnosis of abscess, their findings may not be generalizable to pediatric population. indeed, we found that the sensitivity and specificity of point-of-care ultrasonography for diagnosis of abscess are lower in pediatric cases compared to adult patients; therefore, we believe that this approach of subramanian et al. misrepresents the reported results for diagnostic performance of this imaging modality. the role this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e49 of point-of-care ultrasonography in diagnosis of abscess is particularly crucial for the pediatric cases because they may not tolerate sedation and incision and drainage. since we found that point-of-care ultrasonography has acceptable diagnostic characteristics for diagnosis of abscess in pediatric cases, its use may reduce the rate of unnecessary painful and anxiety-provoking treatment (16, 17). similar to the study of subramaniam et al., in another systematic review and meta-analysis by alsaawi et al. (18) the data of only four studies were pooled to estimate the diagnostic characteristics of point-of-care ultrasonography for diagnosis of abscess. however, this study described the range of diagnostic characteristics of point-of-care ultrasonography and the overall pooled estimates of these variables were not reported. 5. limitations we acknowledge some limitations in our systematic review and meta-analysis of the studies investigating the diagnostic characteristics of point-of-care ultrasonography for diagnosis of abscess. first, we found significant heterogeneity among the included studies. although this was in part addressed by conducting subgroup analysis on pediatric and adult’s patients, other factors such as lack of a common follow-up and difference in the use of index test may also contribute to heterogeneity. second, some of the included studies were rated as unclear or high risk of bias on the patient selection and flow and timing domains. third, the vast majority of the included studies had small sample sizes and the data of two studies were not extractable for meta-analysis. therefore, further original studies with improved methods of patient selection and higher sample sizes are required to establish the results of this metaanalysis. 6. conclusion our meta-analysis demonstrated that point-of-care ultrasonography has excellent diagnostic value for abscess diagnosis in emergency departments. furthermore, we found that the diagnostic performance of point-of-care ultrasonography in diagnosis of abscess was higher for adult cases than for pediatric patients. however, since the conclusion of this meta-analysis was based on a limited number of studies with small sample sizes, further investigations are required to establish point-of-care ultrasonography for diagnosis of abscess in all age groups. 7. declarations 7.1. acknowledgments the authors thank all those who contributed to this study. 7.2. conflict of interest none. 7.3. funding and support none. 7.4. authors’ contribution all authors contributed to study design, data collection, and writing the draft of the study. all authors read and approved the final version of manuscript. 7.5. data availability not applicable. 7.6. using artificial intelligence chatbots none. references 1. hersh al, chambers hf, maselli jh, gonzales r. national trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. arch intern med. 2008;168(14):1585-91. 2. ray gt, suaya ja, baxter r. incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a u.s. population: a retrospective population-based study. bmc infect dis. 2013;13:252. 3. knaysi g, ringelberg j, stadlberger n, soucy z. point of care ultrasound use by associate providers for differentiating abscess versus cellulitis skin and soft tissue infection in the emergency department. j emerg med. 2021;60(1):e1-e7. 4. singer aj, talan da. management of skin abscesses in the era of methicillin-resistant staphylococcus aureus. n engl j med. 2014;370(11):1039-47. 5. stevens dl, bisno al, chambers hf, dellinger ep, goldstein ej, gorbach sl, et al. practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. clin infect dis. 2014;59(2):e10-52. 6. barbic d, chenkin j, cho dd, jelic t, scheuermeyer fx. in patients presenting to the emergency department with skin and soft tissue infections what is the diagnostic accuracy of point-of-care ultrasonography for the diagnosis of abscess compared to the current standard of care? a systematic review and meta-analysis. bmj open. 2017;7(1):e013688. 7. chau cl, griffith jf. musculoskeletal infections: ultrasound appearances. clin radiol. 2005;60(2):149-59. 8. marin jr, dean aj, bilker wb, panebianco nl, brown nj, alpern er. emergency ultrasound-assisted examination this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 6 of skin and soft tissue infections in the pediatric emergency department. acad emerg med. 2013;20(6):545-53. 9. tayal vs, hasan n, norton hj, tomaszewski ca. the effect of soft-tissue ultrasound on the management of cellulitis in the emergency department. acad emerg med. 2006;13(4):384-8. 10. quraishi ms, o’halpin dr, blayney aw. ultrasonography in the evaluation of neck abscesses in children. clin otolaryngol allied sci. 1997;22(1):30-3. 11. levine mc, arroyo a, likourezos a, homel p, dickman e. the use of point of care ultrasound in the evaluation of pediatric soft tissue neck masses. am j emerg med. 2019;37(8):1466-9. 12. adams cm, neuman mi, levy ja. point-of-care ultrasonography for the diagnosis of pediatric soft tissue infection. j pediatr. 2016;169:122-7. e1. 13. lam sh, sivitz a, alade k, doniger sj, tessaro mo, rabiner je, et al. comparison of ultrasound guidance vs. clinical assessment alone for management of pediatric skin and soft tissue infections. j emerg med. 2018;55(5):693-701. 14. gaspari rj, sanseverino a, gleeson t. abscess incision and drainage with or without ultrasonography: a randomized controlled trial. ann emerg med. 2019;73(1):17. 15. subramaniam s, bober j, chao j, zehtabchi s. point-ofcare ultrasound for diagnosis of abscess in skin and soft tissue infections. acad emerg med. 2016;23(11):1298306. 16. uspal ng, klein ej, tieder js, oron ap, simon td. variation in the use of procedural sedation for incision and drainage of skin and soft tissue infection in pediatric emergency departments. hosp pediatr. 2015;5(4):185-92. 17. uspal ng, marin jr, alpern er, zorc jj. factors associated with the use of procedural sedation during incision and drainage procedures at a children’s hospital. am j emerg med. 2013;31(2):302-8. 18. alsaawi a, alrajhi k, alshehri a, ababtain a, alsolamy s. ultrasonography for the diagnosis of patients with clinically suspected skin and soft tissue infections: a systematic review of the literature. eur j emerg med. 2017;24(3):162-9. 19. mower wr, crisp jg, krishnadasan a, moran gj, abrahamian fm, lovecchio f, et al. effect of initial bedside ultrasonography on emergency department skin and soft tissue infection management. ann emerg med. 2019;74(3):372-80. 20. greenlund lj, merry sp, thacher td, ward wj. primary care management of skin abscesses guided by ultrasound. am j med. 2017;130(5):e191-e3. 21. berger t, garrido f, green j, lema pc, gupta j. bedside ultrasound performed by novices for the detection of abscess in ed patients with soft tissue infections. am j emerg med. 2012;30(8):1569-73. 22. iverson k, haritos d, thomas r, kannikeswaran n. the effect of bedside ultrasound on diagnosis and management of soft tissue infections in a pediatric ed. am j emerg med. 2012;30(8):1347-51. 23. sivitz ab, lam sh, ramirez-schrempp d, valente jh, nagdev ad. effect of bedside ultrasound on management of pediatric soft-tissue infection. j emerg med. 2010;39(5):637-43. 24. squire bt, fox jc, anderson c. abscess: applied bedside sonography for convenient evaluation of superficial soft tissue infections. acad emerg med. 2005;12(7):601-6. 25. page-wills c, simon bc, christy d, levitt ma. utility of ultrasonography on emergency department management of suspected cutaneous abscess. acad emerg med. 2000;7(5):493. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e49 table 1: the main characteristics of the studies included in the meta-analysis authors year# country type location population age (year) female % prevalence of abscess reference standard knaysi et al. (3) 2020 lebanon obs ed adults 46 * 46.8 42 i&d or follow-up gaspari et al. (14) 2019 usa ct ed adults 32.5 43 nr i&d or follow-up mower et al. (19) 2019 usa obs ed adults and pediatrics 36 52 68 i&d or follow-up levine et al. (11) 2019 usa obs ped pediatrics 5.3 37% 30 radiology department imaging lam et al. (13) 2018 usa obs ed pediatrics nr nr 58 i&d or follow-up greenlund et al. (20) 2017 usa obs clinic nr nr nr nr nr adams et al. (12) 2016 usa obs ped pediatrics 7* 54% 68 i&d or follow-up marin et al. (8) 2013 usa obs ped pediatrics 7* 57% 62 i&d berger et al. (21) 2012 usa obs ed adults nr nr 85 i&d iverson et al. (22) 2012 usa obs ped pediatrics 5.2 64% 62 i&d sivitz et al. (23) 2010 usa obs ped pediatrics 9.5 42% 44 i&d or follow-up tayal et al. (9) 2006 usa obs ed adults 42 47 43 i&d or follow-up squire et al. (24) 2005 usa obs ed adults 39 31% 60 i&d or follow-up page-wills et al. (25) 2000 usa obs ed nr nr nr 71 i&d quraishi et al. (10) 1997 ireland obs ped pediatrics 1.95 56% 74 i&d or follow-up all included studies had prospective design; age is presented as mean except in studies marked with “*” which is presented as median. #: year of publication; ed: emergency department; ped: pediatric ed; ct: clinical trial; obs: observational; i&d: incision and drainage; nr: not reported; usa: united states of america. table 2: quality assessment of the included studies using quadas-2 tool study risk of bias applicability concerns patient selection index test reference standard flow and timing patient selection index test reference standard knaysi et al. § § gaspari et al. ? ? mower et al. ? levine et al. ? ? lam et al. ? ? greenlund et al. ? ? ? adams et al. ? ? marin et al. ? ? berger et al. ? iverson et al. ? § § sivitz et al. ? ? tayal et al. ? ? squire et al. ? ? page-wills et al. ? § ? quraishi et al. ? ? : low risk; §: high risk; ?: unclear risk. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 8 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flowchart of the literature search and selection of studies that reported accuracy of point-of-care ultrasonography for diagnosis of abscess. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e49 figure 2: preferred reporting items for systematic reviews and meta-analyses (prisma) flowchart of the literature search and selection of studies that reported accuracy of point-of-care ultrasonography for diagnosis of abscess. figure 3: forest plot of the pooled specificity of point-of-care ultrasonography for diagnosis of abscess. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 10 figure 4: forest plot of the pooled positive likelihood ratio (lr) of point-of-care ultrasonography for diagnosis of abscess. ci: confidence interval. figure 5: forest plot of the pooled negative likelihood ratio (lr) of point-of-care ultrasonography for diagnosis of abscess. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e49 figure 6: forest plot of the diagnostic odds ratio (or) of point-of-care ultrasonography for diagnosis of abscess. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index e. rahmani et al. 12 figure 7: summary receiver-operating characteristic (sroc) curve of point-of-care ultrasonography for diagnosis of abscess. auc: area under the curve. se: standard error. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e49 figure 8: funnel plot of publication bias on the pooled diagnostic odds ratio of point-of-care ultrasonography for diagnosis of abscess. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 48 emergency (2015); 3 (2): 48-49 educational part 1: simple definition and calculation of accuracy, sensitivity and specificity alireza baratloo1, mostafa hosseini2, ahmed negida3*, gehad el ashal4 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 3. faculty of medicine, zagazig university, zagazig, egypt. 4. faculty of medicine, cairo university, cairo, egypt. *corresponding author: ahmed negida; faculty of medicine, zagazig university,el-kanayat, el-sharkia, zagazig, egypt. tel: +201125549087; email: ahmed01251@medicine.zu.edu.eg received: december 2014; accepted: february 2015 introduction: mergency physicians, like other specialists, are faced with different patients and various situations every day. they have to use ancillary diagnostic tools like laboratory tests and imaging studies to be able to manage them (1-8). in most cases, numerous tests are available. tests with the least error and the most accuracy are more desirable. the power of a test to separate patients from healthy people determines its accuracy and diagnostic value (9). therefore, a test with 100% accuracy should be the first choice. this does not happen in reality as the accuracy of a test varies for different diseases and in different situations. for example, the value of d-dimer for diagnosing pulmonary embolism varies based on pre-test probability. it shows high accuracy in low risk patient and low accuracy in high risk ones. the characteristics of a test that reflects the aforementioned abilities are accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios (9-11). in this educational review, we will simply define and calculate the accuracy, sensitivity, and specificity of a hypothetical test. definitions: patient: positive for disease healthy: negative for disease true positive (tp) = the number of cases correctly identified as patient false positive (fp) = the number of cases incorrectly identified as patient true negative (tn) = the number of cases correctly identified as healthy false negative (fn) = the number of cases incorrectly identified as healthy accuracy: the accuracy of a test is its ability to differentiate the patient and healthy cases correctly. to estimate the accuracy of a test, we should calculate the proportion of true positive and true negative in all evaluated cases. mathematically, this can be stated as: accuracy = tp + tn tp + tn + fp + fn sensitivity: the sensitivity of a test is its ability to determine the patient cases correctly. to estimate it, we should calculate the proportion of true positive in patient cases. mathematically, this can be stated as: sensitivity = tp tp + fn specificity: the specificity of a test is its ability to determine the healthy cases correctly. to estimate it, we should calculate the proportion of true negative in healthy cases. mathematically, this can be stated as: specificity = tn tn + fp examples: scenario 1 imagine we have a sample of 100 cases, 50 healthy and the others patient. if a test can be positive for all patients and be negative for all the healthy ones, it is 100% accurate. in figure 1, arrow shows the test and it has been able to differentiate the healthy and patient exactly. in this example, the sensitivity of the test is 50 divided by 50 or 100% and its specificity in determining the healthy people is 50 divided by 50 or 100%. taking into account the mentioned statistical characteristics, this test is appropriate for both screening and final verification of a disease. figure 1: a schematic presentation of an example test with 100% accuracy, sensitivity, and specificity. e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 49 baratloo et al figure 2: a schematic presentation of an example test with 75% accuracy, 50% sensitivity, and 100% specificity. scenario 2 if the test can only diagnose 25 out of the 50 patients and has reported the others as healthy (figure 2); accuracy, sensitivity, and specificity will be as follows: accuracy: of the 100 cases that have been tested, the test could determine 25 patients and 50 healthy cases correctly. therefore, the accuracy of the test is equal to 75 divided by 100 or 75%. sensitivity: from the 50 patients, the test has only diagnosed 25. therefore, its sensitivity is 25 divided by 50 or 50%. specificity: from the 50 healthy people, the test has correctly pointed out all 50. therefore, its specificity is 50 divided by 50 or 100%. according to these statistical characteristics, this test is not suitable for screening purposes; but it is suited for the final confirmation of a disease. scenario 3 this time we will assume that the test has been able to identify 25 of the 50 healthy cases and has reported the others as patients (figure 3). in this scenario accuracy, sensitivity and specificity will be as follows: accuracy: of the 100 cases that have been tested, the test could identify 25 healthy cases and 50 patients correctly. therefore, the accuracy of the test is equal to 75 divided by 100 or 75%. sensitivity: from the 50 patients, the test has diagnosed all 50. therefore, its sensitivity is 50 divided by 50 or 100%. specificity: from the 50 healthy cases, the test has correctly pointed out only 25. therefore, its specificity is 25 divided by 50 or 50%. according to these statistical characteristics, this test is suited for screening purposes but it is not suitable for the final confirmation of a disease. acknowledgments: we would like to thank dr. saeed safari and dr. mahmoud yousefifard for their invaluable helps. conflict of interest: none figure 3: a schematic presentation of an example test with 75% accuracy, 100% sensitivity, and 50% specificity. funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. aminiahidashti h, hosseininejad sm, montazer h, et al. diagnostic accuracy of ascites fluid gross appearance in detection of spontaneous bacterial peritonitis. emergency. 2014;2(3):138-40. 2. ojaghi haghighi sh, morteza begi hr, sorkhabi r, et al. diagnostic accuracy of ultrasound in detection of traumatic lens dislocation. emergency. 2014;2(3):121-4. 3. taghizadieh a, ala a, rahmani f, nadi a. diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report. emergency. 2015. [in press]. 4. amini a, eghtesadi r, feizi am, et al. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. emergency. 2013;1(1):15-9. 5. heydari f, esmailian m, dehghanniri m. diagnostic accuracy of ultrasonography in the initial evaluation of patients with penetrating chest trauma. emergency. 2014;2(2):81-4. 6. kariman h, joorabian j, shahrami a, alimohammadi h, noori z, safari s. accuracy of emergency severity index of triage in imam hossein hospital-tehran, iran (2011). j gorgan uni med sci. 2013;15(1):115-20. [persian]. 7. alavi-moghaddam m, safari s, najafi i, hosseini m. accuracy of urine dipstick in the detection of patients at risk for crushinduced rhabdomyolysis and acute kidney injury. eur j emerg med. 2012;19(5):329-32. 8. shojaee m, faridaalaee g, yousefifard m, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chin j traumatol. 2014;17(1):19-24. 9. šimundić a-m. measures of diagnostic accuracy: basic definitions. med biol sci. 2008;22(4):61-5. 10. altman d, bland j. statistics notes: diagnostic tests 1: sensitivity and specificity. bmj. 1994;308(6943):1552. 11. davidson m. the interpretation of diagnostic tests: a primer for physiotherapists. aust j physiother. 2002;48(3):227-32. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 83 emergency (2015); 3 (3): 83-86 editorial medical journalism and emergency medicine saeed safari1, alireza baratloo1*, mahmoud yousefifard2 1. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of physiology, school of medicine, tehran university of medical sciences, tehran iran. *corresponding author: alireza baratloo; department of emergency medicine, shohadaye tajrish hospital, tehran, iran. postal code: 1989934148; tel: +989122884364; fax: +982122721155; email: alirezabaratloo@yahoo.com received: may 2015; accepted: may 2015 introduction: owadays, many researches in the field of medicine are conducting all around the world and medical journalism is a way to share the results. in fact, dissemination of the related manuscripts can prevent the repetitive research or may even lead to conducting a better survey. therefore high quality medical journals are considered as up-to-date resources for further investigations (1, 2). medical journals are propagating their papers in various media including television programs, newspapers, internet websites and different social media. so they can influence the government policy makers, health-care professionals and even public (3-5). moreover, most researchers hear about medical discoveries for the first time through medical journals and their related social media. so as well a high quality journal can help to improve medical science, a journal of poor quality can be damaging and distorting. indeed, popular journals have the power of inventing a “communication storm” to draw attention to a certain topic. thus they have to respect the accepted international principles to prevent spreading inaccurate and misleading data (6, 7). this paper aims to review the previous and current situation of medical journalism by focus on field of emergency medicine. history of medical journalism: journalism was considered as an innovation in the field of medicine in late eighteenth and early nineteenth century. it was a way to share the researchers' experiences. with progression of the technology, medical journalism became a new element of disseminating medical information and help to accelerate the processes of medical changes (8). history of scientific journalism started by “journal des scavans” in paris, and “philosophical transactions” in london in 1665 and both are existing today, after three and a half centuries." journal des scavans" was edited by denis de sallo and included book reviews, while" philosophical transactions" was edited by henry oldenburg and involved scientific news (9). the first peer-review collection of medical articles was published by "royal society of edinburgh" in 1731, in scotland. it seems that it was the start point of the professional medical journalism. they named their journal as “medical essays and observation” which was published in five volumes. but in 1737 they spread their scope and covered the art, philosophy and particularly natural knowledge as well and were identified as philosophical society of edinburgh (10, 11). “medical repository” was the first american medical journal, which founded in 1797. it was published quarterly and ceased publication in 1824 after 27 years. loss of institutional support, prohibitive costs and lack of wishful editors were probably influenced factors on the journal breakdown (12, 13). john collins warren along with james jackson founded “new england journal of medicine and surgery and collateral branches of science" as a medical and philosophical journal in september 1811 and published the first issue in january 1812. after a series of events and because of financial difficulties finally, the massachusetts medical society purchased it in 1921 for 1 dollar and renamed it to “the new england journal of medicine” in 1928. this journal that named briefly as nejm, is still being published by the massachusetts medical society and is among the most n table 1: the first medical journals in all around the world journal name inception date medical essays and observation 1731 medical repository 1797 new england journal of medicine 1812 lancet 1823 british medical journal 1840 jama 1883 chinese medical journal 1887 journal of the american medical association http://en.wikipedia.org/wiki/united_states http://en.wikipedia.org/wiki/medical_journal http://en.wikipedia.org/wiki/john_collins_warren http://en.wikipedia.org/wiki/john_collins_warren http://en.wikipedia.org/wiki/massachusetts_medical_society this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com safari et al 84 reputable and trust worthy peer-reviewed medical jour nals and the oldest continuously published ones (14). after nearly two consecutive centuries, today a beautiful motto is inscribed with the name of this journal, "innovation today for the promise of tomorrow". “the lancet” is another senior medical journal that has rare reputation. it was established by an english surgeon named as thomas wakley in 1823 and has been owned by elsevier since 1991. in 2013 journal citation reports, the lancet s impact factor was ranked second among general medical journals (39.207) after the new england journal of medicine (54.420). 2013 journal citation report science edition, thompson reuters, 2014. some other famous journals have contributed in shaping the history of medical journals. their names, alongside with those previously mentioned and their date of inception are summarized in table 1. medical journalism in iran: journalism in iran was started by “mirza saleh shirazi” who published “kaghaz-e akhbar” in 1837 in tehran. thereafter “vaghaee-etefaghieh ”was started to publish in 1851, in tehran that included some medical news and public health topics along with the others(15). based on available resources, it seems that “hefz-o-sehheh” which was published by the society of public health (anjomane hefz-o-sehheh) in 1901, was the first medical journal in iran. dr. ali asghar nafisi was the first physician to establish a medical journal named as “hefz-o-sehheh” in 1906; also had the same name but differ from that published in 1901."iranian ministry of health and charity affairs" (vezarat-e sehhyeh va omuor-e kheiryyeh) started to publish the earliest state medical journal in 1921, named as "sehhyeh and omuor-e kheiryyeh". as an innovation, the physicians were invited to submit their papers in the first issue of this journal (15). there were some other medical journals before 1934, the date of foundation of tehran university medical school, which may be considered as a revolution in medicine and medical journalism in iran. their names and date of inception are summarized in table 2. based on the iranian medical journals database, www.research.ac.ir/journals, today 347 active medical journals are available in iran. table 3 shows the baseline features of these journals. table 2: the first medical journals in iran journal name date of inception founder hefz-o-sehheh 1901 society of public health hefz-o-sehheh 1906 dr. ali asghar nafisi tebabat 1908 mirza ebrahim khan sehhat 1909 seyyed hossein khan edalat tebb-e mossavar 1916 mozayyan-ol-soltan tebbi 1919 mohammad khan alim-0-doweleh tebbkonuni 1920 dr. fatah ali khan sehhyeh and omuore kheiryyeh 1921 ministry of sehhyeh &omuore kheiryyeh tebabat 1922 mirza ahmad khan tebbjadid 1923 unknown sehhat 1924 unknown red lion and sun journal 1925 red sun and lion society nedayesehhat 1927 dr. seyyed razi sehhat davasazi 1927 dr. fatolla farrahi sehhat nemaye iran 1933 dr. mohammad ali totiya table 3: baseline features of iranian medical journals characteristics n (%) indexing web of science 22 (5.1) pubmed 42 (9.8) scopus 103 (24) embase 111 (25.9) unknown 319 (74.2) language english 232 (54) persian 198 (46) frequency weekly 2 (0.5) monthly 21 (4.9) bimonthly 37 (8.6) quarterly 255 (59.3) biannually 30 (7) annually 2 (0.5) rank scientific/research 292 (67.6) http://en.wikipedia.org/wiki/peer-reviewed http://en.wikipedia.org/wiki/medical_journal http://en.wikipedia.org/wiki/medical_journal http://en.wikipedia.org/wiki/surgeon http://en.wikipedia.org/wiki/thomas_wakley http://en.wikipedia.org/wiki/elsevier http://en.wikipedia.org/wiki/elsevier http://en.wikipedia.org/wiki/journal_citation_reports http://en.wikipedia.org/wiki/impact_factor http://en.wikipedia.org/wiki/the_new_england_journal_of_medicine http://en.wikipedia.org/wiki/the_new_england_journal_of_medicine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 85 emergency (2015); 3 (3): 83-86 emergency medicine journals: on september 21, 1979 by positive vote of american board of medical specialties, emergency medicine was introduced as a medical specialty to the world. emergency medicine is the specialty that due to its nature faced with a variety of patients, so was able to convince medical journals to pay special attention to it. the story does not end here and special journals dedicated to the emergency medicine. top 10 active journals in the field of emergency medicine are summarized in table 4. iranian emergency medicine journals: iranian society of emergency medicine (isem) was developed in 2002. it is obvious that emergency medicine is a young field in iran and despite abundant oppositions continues to grow and progress. despite the youth field in iran, many of iranian journals have included this topic in their respective fields (table 5). our frequent problems in medical journalism: frequent problems and obstacles in progression and qualifying of medical journalism could be categorized to five headings: problems related to authors, reviewers, editors, editor-in-chief, and managing editor (table 6). despite of old history of medical journalism in the world, it is recently mentioned as a professional topic in iran. solving the above-mentioned problems should be considered as the most important way for improving and qualifying the medical journalism in iran. training courses of professional medical journalism for editorial boards, public and mandatory scientific writing educations for medical students and education of critical appraisal skills for reviewers can be helpful in this regard. conclusion: historically, iranian population have great defect in documentation of their findings and mostly rely on their memory. anything that is not written will be forgotten and anything that is forgotten, never been existed. so write to persist the knowledge, never late to mend. acknowledgment: the authors would like to thank dr. saeid safari, department of anesthesiology and pain medicine, iran university of medical sciences, tehran, iran for his valuable cooperation. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. table 4: top 10 emergency medicine journals rank title country 1 resuscitation ireland 2 annals of emergency medicine united states 3 academic emergency medicine united kingdom 4 shock united states 5 prehospital emergency care united kingdom 6 current heart failure reports united states 7 congestive heart failure united kingdom 8 injury united kingdom 9 scandinavian journal of trauma, resuscitation and emergency medicine united kingdom 10 critical care and resuscitation australia table 5: iranian emergency medicine journals journal name since frequency pubmed journal of military medicine 1999 quarterly trauma monthly 2006 quarterly √ journal of injury and violence research 2009 biannually √ archive of trauma research 2012 quarterly √ bulletin of emergency and trauma 2013 quarterly journal of safety promotion and injury prevention 2013 quarterly emergency 2013 quarterly √ journal of emergency practice and trauma 2014 quarterly iranian journal of emergency medicine 2014 quarterly http://isem.ir/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com safari et al 86 references: 1. godlee f, jefferson t, callaham m, et al. peer review in health sciences. london: bmj books london; 2003. p. 19. 2. phillips dp, kanter ej, bednarczyk b, tastad pl. importance of the lay press in the transmission of medical knowledge to the scientific community. n engl j med. 1991;325(16):1180-3. 3. larsson a, oxman ad, carling c, herrin j. medical messages in the media–barriers and solutions to improving medical journalism. health expect. 2003;6(4):323-31. 4. laurent mr, vickers tj. seeking health information online: does wikipedia matter? j am med inform assoc. 2009;16(4):471-9. 5. cassels ak. the media-medicine mix: quality concerns in medical reporting. open med. 2007;1(1):e52. 6. carducci a, alfani s, sassi m, cinini a, calamusa a. mass media health information: quantitative and qualitative analysis of daily press coverage and its relation with public perceptions. patient educ couns. 2011;82(3):475-8. 7. dentzer s. communicating medical news—pitfalls of health care journalism. n engl j med. 2009;360(1):1-3. 8. cassedy jh. the flourishing and character of early american medical journalism, 1797–1860. j hist med allied sci. 1983;38(2):135-50. 9. banks d. starting science in the vernacular. notes on some early issues of the philosophical transactions and the journal des sçavans, 1665-1700. asp la revue du geras. 2009;55:5-22. 10. awais sm. science and scope of peer review. annals. 2008;14(2):42. 11. campbell n, smellie rms, cameron p. the royal society of edinburgh(1783-1983). the first two hundred years. 1 ed. london: the royal society of edinburgh; 1983. p. 186. 12. kahn rj, kahn pg. the medical repository--the first us medical journal (1797-1824). n engl j med. 1997;337(26):1926-30. 13. billings js. iv. literature and institutions. am j med sci. 1876;144:439-80. 14. waters hf-g. the new england historical and genealogical register. london: new england historic genealogical society; 1934. p. 112. 15. azizi m-h, raees-jalali g-a, noroozi h. a brief history of the publication of biomedical journals in iran between 1901 and 1979. arch iran med. 2009;12(2):204. table 6: frequent problems in medical journalism problems related to authors  low quality articles  rejected manuscript from other journals  nonprofessional authors  submission errors  bad structures  no appropriate reply to reviewer problems related to reviewers  perfect review for bad articles  poor review for good articles  walking on a narrow edge of decision problems related to editors  solitary associate editors  non-strategic leaders  high expectations from primitive system  play in separate teams  understanding of real position and editors-inchief mission problems related to editor in chief  to be or not to be? that’s the question  unrealistic target  leader with no follower  setting time and human resource-oriented strategies  poor cooperation with system  not having rules  decision making problems related to managing editor  low scientific relation with journal title  unfamiliar with strategic planning  unfamiliar with potential power of the role  unable to connect all editors predefined strategy  lack of communication skills  monitoring of the play with information technology based modalities  poor time table  right plans will be wrong in action emergency 2016; 4 (2): 92-96 or i g i n a l re s e a rc h remifentanil versus fentanyl/midazolam in painless reduction of anterior shoulder dislocation; a randomized clinical trial mohammad gharavifard1, azadeh tafakori1∗, hamid zamani moghadam2 1. anesthesia department, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, mashhad university of medical sciences, mashhad, iran. received: may 2015; accepted: september 2015 abstract: introduction: performance of painful diagnostic and therapeutic procedures is common in emergency department (ed), and procedural sedation and analgesia (psa) is a fundamental skill for every emergency physician. this study was aim to compare the efficacy of remifentanil with fentanyl/midazolam in painless reduction of anterior shoulder dislocation. methods: in this randomized, double blind, clinical trial the procedural characteristics, patients satisfaction as well as adverse events were compared between fentanyl/midazolam and remifentanil for psa of 18–64 years old patients, which were presented to ed following anterior shoulder dislocation. results: 96 cases were randomly allocated to two groups (86.5% male). there were no significant difference between groups regarding baseline characteristics. remifentanil group had lower duration of procedure (2.5 ± 1.6 versus 4.6±1.8 minutes, p < 0.001), higher pain reduction (53.7±13.3 versus 33.5±19.6, p < 0.001), lower failure rate (1 (2.1%) versus 15 (31.3%), p < 0.001), higher satisfaction (p = 0.005). adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p = 0.122). conclusion: it seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulder dislocation. keywords: conscious sedation; midazolam; fentanyl; remifentanil [supplementary concept]; shoulder dislocation © copyright (2015) shahid beheshti university of medical sciences cite this article as: gharavifard m, tafakori a, zamani moghadam h. remifentanil versus fentanyl/midazolam in painless reduction of anterior shoulder dislocation; a randomized clinical trial. emergency. 2016; 4(2):92-96. 1. introduction p erformance of painful diagnostic and therapeutic procedures is common in emergency department (ed), and procedural sedation and analgesia (psa) is a fundamental and required skill for every emergency physician (1, 2). with the wide range of procedures and high patient population, the ability to individualize psa and maximize the risk/benefit ratio for each unique situation is essential (3). one of the common painful procedures in ed is reduction of dislocated shoulder joints. the glenohumeral joint is the most commonly dislocated major joint in the body. the an∗corresponding author: azadeh tafakori; emergency department, emam reza hospital, mashhad, iran; tel: +989173147528; email: dr.azadeh. tafakori@hotmail.com. nual incidence is 17 per 100,000, and two distinct age peaks are recognized, the first in men 20 to 30 years of age and the second in older women (4). analgesia and muscle relaxation through procedural sedation are often used to facilitate reduction (5). fentanyl combined with midazolam is frequently used as a safe psa agent in ed (3). however, caution must be exercised when using benzodiazepines and opioids together because the risk for hypoxia and apnea is signiïňącantly greater than when either is used alone (6, 7). remifentanil is a relatively new synthetic opioid with a potency comparable to fentanyl but an exceptionally short contextsensitive half-life of only 3–5 minutes (8, 9). however, currently there are insufficient published studies to warrant its routine use. efficacy of remifentanil in combination with other agents is supported by several clinical trials (10–14), but few studies have described the use of remifentanil alone during performing procedures (15–17). the aim of this ranthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com dr.azadeh.tafakori@hotmail.com dr.azadeh.tafakori@hotmail.com 93 emergency 2016; 4 (2): 92-96 domized clinical trial was to compare the efficacy of a pure analgesia-based sedation regimen with remifentanil with a conventional regimen consisting of fentanyl/midazolam for moderate sedation of patients with anterior shoulder dislocation. 2. materials and methods 2.1. study design and settings this study was a prospective, randomized, single-center, parallel group clinical trial, comparing fentanyl/midazolam to remifentanil alone for moderate sedation in patients aged 18–64 years with anterior shoulder dislocation, who were presented to the ed of imam reza hospital, mashhad for closed reduction. this study was approved by the ethics committee of our institute (91/570419 november 4, 2012) and registered in iranian registry of clinical trials under the number irct: 2013011312115n1. informed consent was obtained from all the selected patients after explaining the study. 2.2. participants the studied subjects were selected using convenience sampling among the patients presented to the ed of a universityaffiliated tertiary care medical center over a 9-month period between february 2013 and october 2013, with anterior shoulder dislocation and requiring closed reduction. those aged 18–64 years with physical condition i (healthy and normal patients without previous medical history) and ii (patients with mild systemic disease with no functional limitation) according to the classification of american society of anesthesiologists (asa) were enrolled. all subjects with history of allergy to benzodiazepines and narcotics; prolonged use of opioids or alcohol; consumption of sedative or analgesic drugs before presenting to ed; sleep obstructive apnea syndrome; maxillofacial malformations with high probability of airway maintenance failure; pregnant; anterior dislocation requiring referral to orthopedic operating room; severe trauma and unstable hemodynamics; advanced heart disease; kidney failure; pneumonia; uncontrolled seizures; and finally patients not willing to participate in the study were excluded. 2.3. intervention using convenience sampling 96 patients were randomized and included in the intention-to-treat analysis, 48 in fentanyl/midazolam group and 48 in remifentanil group. allocation assignments were generated by an online random number generator from http://www.randomizer.org/ and placed in sealed opaque envelopes to be opened in sequential order by research associates. physicians (trained senior emergency medicine residents) and patients were blinded to the type of medication. the investigators doing the analysis were not the same as those administering drugs and performing the procedures. on arrival to the intervention room, where the requirements to protect the airway and prevent aspiration as well as the suitable pulmonary ventilation facilities were predicted, intravenous access, supplementary oxygen via nasal cannula (2 liter/min), routine pulse oximetry and cardiac monitoring were established for all the patients. remifentanil hydrochloride (lyophilized powder in sterile vials each containing 1 m g of the compound) was reconstituted diluted with standard diluent. the pharmacy at the institute supplied the fentanyl and midazolam from commercial stock. the patients in group 1 received remifentanil (1 µg /k g body weight bolus intravenous administration at a concentration of 50 µl /ml , and repeated additional titrated to effect doses of 1 µg /k g administered every minute until the completion of reduction), while those in group 2 received 1.5 µg /k g fentanyl in combination with 0.1 m g /k g midazolam titrated to effect doses intravenously. it should be noted that in this study, the aim of giving the drugs was to achieve moderate sedation or conscious sedation (ramsay sedation score 3), which implied the following: patients only responded to commands; airway intervention was not necessary; spontaneous ventilation of the patients was adequate; and the patients cardiovascular function was maintained. the amount of drugs to give score 3 sedation, was determined by an attending emergency medicine specialist and the patient was judged to be sedated adequately to begin undergoing reduction by him. after sedation, reduction of anterior shoulder was performed by employing traction and counter traction method in both groups. our trained emergency medicine resident rated the pain perceived by the patient before and during the procedure using 100 mm visual analog scale (vas). demographic data were gathered for all patients. the incidence of adverse events was determined by a trained emergency medicine resident and was marked in a checklist that included the following: respiratory adverse events (the need for supplemental oxygen, ventilation with a bag-mask, maneuver practices for maintaining the airway open, insertion of airway, respiratory stimulation, and respiratory depression with spo2 < 92% at any time during intravenous administration of the drug until hospital discharge), and nonrespiratory complications (dysphoria, vomiting, headache, myoclonus, nausea, stiffness, rash, cough, bronchospasm, laryngospasm, stridor, apnea, seizures, restlessness, agitation, and aspiration). at the time of discharge, our trained emergency medicine resident recorded patient satisfaction rate using a likert scale with four options of excellent, good, average, and poor. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com http://www.randomizer.org/ gharavifard et al. 94 2.4. study end-points the primary end-points were pain reduction, procedure time, patient satisfaction, and incidence of respiratory adverse events. secondary end-points included nonrespiratory adverse events. 2.5. definitions a successful reduction was determined clinically by the presence of a palpable clunk, decrease in pain, and improvement in the range of motion. procedure time was defined as time from start of traction to completion of reduction. the timing was measured and recorded using a stopwatch. 2.6. data analysis ibm spss statistics 21 was used for statistical analyses. categorical variables were reported as number and percentage and continuous ones as mean ± standard deviation. chisquare and fisher exact tests were used for comparing categorical variables and t-test for comparing mean between groups. p value < 0.05 was considered statistically significant. 3. results 48 cases received remifentanil and 48 received a combination of fentanyl and midazolam (86.5% male). the mean age of remifentanil patients was 39.7 ± 10.3 years compared to 39.8±9.9 years for fentanyl and midazolam group (p = 0.952). in remifentanil group 41 (85.4%) and in fentanyl and midazolam group 42 (87.5%) cases were male (p = 0.5). the subjects in both groups were stable regarding hemodynamic status. the mean pain score at baseline was 70.3 ± 10.8 mm for fentanyl and midazolam and 76.6 ± 11.9 mm for remifentanil group (p = 0.008). since the minimum clinically significant difference of pain score was considered 30 mm for this study, the baseline difference of pain severity between two groups was not clinically significant. table 1 compares the 2 groups regarding procedure characteristics and observed complications. respiratory adverse event was not experienced in any of the groups. non-respiratory adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p = 0.122). 4. discussion when choosing a strategy for psa, it is important to consider the type of procedure being performed (painful or not), the length of the procedure, specific procedural requirements (anxiolysis vs. immobility), and whether sedation needs to be prolonged. a risk-benefit analysis should be conducted before performing psa and the benefits of reducing anxiety and pain versus the risk of respiratory depression and airway disorders should be measured. the results of the present study demonstrated a significantly lower duration of procedure and lower failure rate in patients that were sedated using remifentanil. on the other hand, the mean pain reduction was significantly higher in remifentanil group. two groups had the same condition regarding respiratory and non-respiratory adverse events. the level of patient satisfaction was significantly higher in remifentanil group. rai et al. studied remifentanil versus propofol for awake fiberoptic intubation and reported signifcantly shorter endoscopy and intubation times for remifentanil group (15). dunn et al. demonstrated that propofol and remifentanil provide excellent sedation and analgesia for the reduction of anterior glenohumeral dislocation (10, 11). in phillips et al. case series an initial bolus dosage of 0.5–3 mc g /k g intravenous remifentanil with subsequent 0.25–1 mc g /k g boluses resulted in mean pain severity of 1.1, mean procedure time of 4 minutes and 17% respiratory complications requiring temporary intervention during procedure (16). the lower mean pain severity during the procedure with remifentanil (9.4 ± 8.5 mm vs. 26.1 ± 20.2 mm) revealed greater effectiveness and potency of this drug. this finding was similar to dunn et al., phillips et al., swann et al., sacchetti et al., and cok oy et al. findings (10, 12, 13, 16, 17). some non-respiratory adverse events have been reported using combination of midazolam/fentanyl (18). application of remifentanil in combination with midazolam for performing painful procedures in children resulted in high and unacceptable rate of hypoxemia (14). the incidence of respiratory and non-respiratory adverse events was similar in both groups of the present study. in this study, significantly higher patient satisfaction was reported for patients sedated with remifentanil, which was compatible with findings of dunn et al. (10). in the present study, for eliminating further confounding factors, the same technique of reduction was performed for all patients in both groups. the study revealed that remifentanil works effectively in psa of patients with anterior shoulder dislocation without addition of any sedative agents. since only adults between the ages of 21 and 64 years were studied, our findings cannot be extrapolated to children and the elderly. 5. conclusion it seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination for procedural sedation and analgesia in anterior shoulder dislocation. the 2 groups had the same condition regarding respiratory and non-espiratory this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 95 emergency 2016; 4 (2): 92-96 table 1: comparison of the 2 studied groups regarding procedure characteristics and observed complications variable fentanyl + midazolam remifentanil p value mean procedure time (minute) 4.6 ± 1.8 2.5 ± 1.6 < 0.001 pain severity during procedure# 36.8 ± 22.9 22.9 ± 9.9 < 0.001 mean pain reduction 33.5 ± 19.6 53.7 ± 13.3 < 0.001 failure rate 15 (31.3) 1 (2.1) < 0.001 non-respiratory adverse events vomiting 2 (4.2) 0 (0) 0.247 nausea 5 (10.4) 1 (2.1) 0.102 itching 2 (4.2) 5 (10.4) 0.218 cough 2 (4.2) 1 (2.1) 0.5 agitation 1 (1.2) 0 (0) 0.5 dysphoria 4 (8.3) 2 (4.2) 0.339 total 12 (25) 8 (16.7) 0.122 patient satisfaction excellent 32 (66.7) 43 (89.6) < 0.005 good 16 (33.3) 5 (10.4) values are presented in mean ± standard deviation or number (%), pain severity was measured based on visual analogue scale (millimeter), failure rate: failure in pain reduction ≥ 30 mm. adverse events. 6. appendix 6.1. acknowledgements the authors appreciate the insightful cooperation of emergency department staff. 6.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 6.3. funding none. 6.4. conflict of interest none. references 1. cordell wh, keene kk, giles bk, jones jb, jones jh, brizendine ej. the high prevalence of pain in emergency medical care. the american journal of emergency medicine. 2002;20(3):165–9. 2. godwin sa, caro da, wolf sj, et al. clinical policy: procedural sedation and analgesia in the emergency department. annals of emergency medicine. 2005;45(2):177–96. 3. marx j, walls r, hockberger r. rosen’s emergency medicine-concepts and clinical practice: elsevier health sciences; 2013. p. 4. chalidis b, sachinis n, dimitriou c, papadopoulos p, samoladas e, pournaras j. has the management of shoulder dislocation changed over time? international orthopaedics. 2007;31(3):385–9. 5. fitch rw, kuhn je. intraarticular lidocaine versus intravenous procedural sedation with narcotics and benzodiazepines for reduction of the dislocated shoulder: a systematic review. academic emergency medicine. 2008;15(8):703–8. 6. mace se, barata ia, cravero jp, et al. clinical policy: evidence-based approach to pharmacologic agents used in pediatric sedation and analgesia in the emergency department. annals of emergency medicine. 2004;44(4):342–77. 7. panzer o, moitra v, sladen rn. pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. anesthesiology clinics. 2011;29(4):587–605. 8. scott l, perry m. remifentanil: a review of its use during the induction and maintenance of general anaesthesia (vol 65, pg 1793, 2005). drugs. 2005;65(16):2286. 9. glass ps, gan tj, howell s. a review of the pharmacokinetics and pharmacodynamics of remifentanil. anesthesia & analgesia. 1999;89(4s):7. 10. dunn m, mitchell r, souza c, drummond g. evaluation of propofol and remifentanil for intravenous sedation for reducing shoulder dislocations in the emergency department. emergency medicine journal. 2006;23(1):57–8. 11. dunn mj, mitchell r, desouza ci, drummond gb, waite a. recovery from sedation with remifentanil and propothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com gharavifard et al. 96 fol, compared with morphine and midazolam, for reduction in anterior shoulder dislocation. emergency medicine journal. 2011;28(1):6–10. 12. swann a, williams j, fatovich dm. recall after procedural sedation in the emergency department. emergency medicine journal. 2007;24(5):322–4. 13. cok oy, ertan a, bahadir m. remifentanil versus fentanyl in combination with midazolam for retrobulbar block in cataract surgery. saudi medical journal. 2008;29(4):544– 8. 14. litman rs. conscious sedation with remifentanil and midazolam during brief painful procedures in children. archives of pediatrics & adolescent medicine. 1999;153(10):1085–8. 15. rai m, parry t, dombrovskis a, warner o. remifentanil target-controlled infusion vs propofol target-controlled infusion for conscious sedation for awake fibreoptic intubation: a double-blinded randomized controlled trial. british journal of anaesthesia. 2008;100(1):125–30. 16. phillips wj, halpin j, jones j, mckenzie k. remifentanil for procedural sedation in the emergency department. annals of emergency medicine. 2009;53(1):163. 17. sacchetti a, jachowski j, heisler j, cortese t. remifentanil use in emergency department patients: initial experience. emergency medicine journal. 2012;29(11):928–9. 18. mamula p, markowitz je, neiswender k, et al. safety of intravenous midazolam and fentanyl for pediatric gi endoscopy: prospective study of 1578 endoscopies. gastrointestinal endoscopy. 2007;65(2):203–10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction materials and methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 8 emergency (2015); 3 (1): 8-15 review article infantile apparent life-threatening events, an educational review hamed aminiahidashti emergency medicine department, mazandaran university of medical sciences, sari, iran *corresponding author: hamed aminiahidashti, emergency department, imam khomeini hospital, amir mazandarani bololivar, sari, iran. tel: +89113540546; email: hamedaminiahidashti@yahoo.com received: october 2014; accepted: december 2014 abstract many physicians have received a frantic call from anxious parents stating that their child had stopped breathing, become limp, or turned blue but then had recovered quickly. an apparent life-threatening event (alte) is defined as “an episode that is frightening to the observer, and is characterized by some combination of apnea, color change, marked change in muscle tone, choking, gagging, or coughing”. the incidence of alte is reported to be 0.05% to 6%. the knowledge about the most common causes and factors associated with higher risk of alte could be resulted in a more purposeful approach, improving the decision making process, and benefiting both children and parents. the aim of this review article was to report the epidemiology, etiology, evaluation, management, and disposition of alte. infants with an alte might present no signs of acute illness and are commonly managed in the emergency settings that often require significant medical attention; hence, the emergency medicine personnel should be aware of the its clinical importance. there is no specific treatment for alte; th erefore, the clinical evaluations should be focused on the detection of the underlying causes, which will define the outcomes and prognosis. alte is a confusing entity, representing a constellation of descriptive symptoms and signs; in other words, it is not a diagnosis. there are multiple possible etiologies and difficulties in evaluating and managing infants with these events, which are challenges to primary care physicians, emergency medicine specialists, and subspecialty pediatricians. the evaluation of these events in infants includes a detailed history, appropriate physical examination, diagnostic tests guided by obtained clues from the history and physical examination, and observation in the emergency department. key words: infantile apparent life-threatening event; death, sudden; pediatrics; emergency medicine cite this article as: aminiahidashti h. apparent life-threatening events, an educational review. emergency. 2015;3(1):8-15. introduction: n apparent life-threatening event (alte) was defined as “an episode that is frightening to the observer and is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, gagging, or coughing” (1, 2). this definition replaced the term “near-miss sudden infant death syndrome” that implied a close association with sudden infant death syndrome (sids) but was subsequently dismissed based on scarce evidence of the overlap between alte and sids. whether sids and alte are strictly correlated is still a major argument among neonatologists (3, 4). although a number of alte risk factors are similar to those of sids, the differences warrant a separate focus on alte beyond that on sids (5). altes presenting to the emergency department (ed) might remain as a single, unexplained event or be attributable to numerous causes, ranging from minor to serious ones (6). knowledge about the most common causes and factors associated with higher risk of alte could result in a more purposeful approach, improving the decision-making process, and benefiting both the infants and their parents (6). infants with alte usually present with an acute and unexpected change in behavior that has alarmed the caregivers (5). they might present with signs of acute illness that usually mandates management in the emergency medicine settings. these patients often require significant medical attention as well as intervention; hence, the emergency medical service (ems) personnel should be aware of the clinical importance of these events to provide timely and thorough medical evaluation and treatment for infants meeting the criteria for an alte (7). demographic data of cases with alte are obtained from children admitted to hospitals or eds and because not all the children are brought for evaluation, the precise incidence of alte is not clear. the reported incidence ranges from 0.05% to 6% or is a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 9 aminiahidashti emergency (2014); 2 (3): ***-*** estimated at 2.4 in every 1000 live births (5, 8, 9). the incidence of alte among neonates is reported to range from 1.57 to 2.46 in every 1000 live births (4, 10). most of the altes occur in children younger than one year old (11, 12). in most published studies, a substantial portion of reported patients with alte were in neonate or at least younger than three months old with 50% to 80% being younger than two to three months old (9, 13-15). the median age was two months and 50% of infants showed normal findings on clinical examinations (16, 17). it has been reported that 2.27% of hospitalized children are the infants with alte (18). based on above-mentioned, the aim of this review was to present the epidemiology, etiology, evaluation, management, and disposition of alte. etiology the underlying etiology of alte varies and an episode of alte should be considered the manifestation of other conditions rather than a diagnosis. an etiology would be found in one-half of patients, implying a potential for an intervention that could eliminate further events. the most frequent problems associated with alte are gastrointestinal (50%), neurologic (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (< 5%), or other problems such as child abuse. despite through evaluations, no specific diagnosis would be made for the remaining patients, i.e. idiopathic cases (2, 19). the approach to investigate and manage an alte during admission is unstructured. a large number of patients are discharged from the ed and inpatient service with different diagnoses, mostly with convulsion, febrile convulsion, gastroesophageal reflux disease (gerd), and lower respiratory tract infection. the diagnosis changes in those attending more than once for alte (16). alte might occur in the first 24 hours of birth, particularly within the first two hours. events are often related to a potentially asphyxiating position. parents might be too fatigued or unable to assess their infant's condition correctly (20). of the infants with alte, 83.3% appeared to be in no distress, 13.3% mild, and 3.3% moderate distress. in most patients, findings of the general appearance and vital signs were not clinically abnormal (7). differential diagnosis the alte might be associated with a variety of underlying diseases (21). epidemiologic studies found that the most frequent causes of alte were consecutively gerd, respiratory infections, and seizures (22, 23). table1 lists the common, uncommon, and rare diagnoses assigned to patients with alte. common causes are discussed independently (19, 21-23)(table 1). gastroesophageal reflux disease gerd was the most common diagnosis among patients with alte (24). gerd induces significant histopathologic changes in larynx mucosa (25). given the temporal correlation between peak age of alte and that of gerd, and the fact that reflux of gastric contents into the hypopharynx can trigger laryngospasm, a diagnosis of gerd provides an easy explanation for an alte. however, researchers have been unable to demonstrate a temporal association between episodes of gerd on ph probe and altes or apneic events (26, 27). respiratory disorders respiratory disorders are another common diagnosis in patients with alte; however, the frequency of diagnosis is widely varied (28). this might be due to epidemic bronchiolitis, pertussis, or lower respiratory tract infections (29). up to 20% of infants younger than six months old, who were hospitalized due to infection with respiratory syncytial virus (rsv) had apnea and this association was strongest during the first month of life and in preterm neonates (30). apnea occurred in 0.5% to 12.0% of children younger than two years of age with pertussis (31, 32). in infants with alte, prolonged respiratory events are associated with ineffective esophageal motilities, characterized by frequent primary peristalsis and significant propagation failure, which is suggestive of dysfunctional regulation of swallow-respiratory junction interactions. hence, treatment should target the proximal aerodigestive tract rather than gerd (33). seizures seizures are diagnosed in 4% to 7% of infants with alte (34). alte might be the first sign of an epileptic seizure. diagnosis is often difficult because the interictal electroencephalogram (eeg) findings are usually normal or show nonspecific changes; moreover, gerd table 1: reported final diagnoses for patients with apparent life-threatening events common less common rare reported gastroesophageal reflux disease seizure/febrile seizure upper/lower respiratory tract infection misinterpretation of benign process such as periodic breathing vomiting/choking episode pertussis inflicted injury poisoning serious bacterial infection electrolyte abnormality arrhythmia or other cardiovascular diseases anemia breath-holding spell metabolic diseases anatomic maxillofacial obstruction this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (1): 8-15 10 might mimic these events (35). during the etiologic investigation of alte, first seizures and epilepsy should be included in the differential diagnosis and ictal recordings would be important tools to confirm these diagnoses (36-38). seizures are secondary to underlying causes such as congenital brain malformation, metabolic disorders, electrolyte abnormalities, prenatally acquired brain injury, or intracranial bleeding (including nonaccidental head trauma); therefore, these possibilities must be considered during assessments (39). trauma the diagnosis of child abuse should be considered in patients with alte. the evaluation of altes should include funduscopic examination as altes and retinal hemorrhages are associated with child abuse. retinal hemorrhage was detected in 1.4% of infants with altes (40). the diagnosis of inflicted traumatic head injury cannot rely on the finding of retinal hemorrhage alone, but the finding of severe bilateral retinal hemorrhage particularly with retinal folds or detachments is suggestive of the diagnosis (41). child abuse was detected in 2.3% of patients with alte (40). infant with inflicted head injury might appear well on presentation with no external signs of abuse (42, 43); hence, inflicted head injury must be considered in a patient who has an alte unless an alternative cause is readily apparent (14). poisoning a large number of children referred to the ed with alte had positive toxicology screening results. in particular, a number of these children were found to be given an over-the-counter cold medicine. the most frequently detected medications were acetaminophen, amphetamine, benzodiazepines, cocaine, codeine, meperidine, methadone, phenobarbital, and phenothiazine (44, 45). thus, toxicological screening tests should be included in routine evaluation of children with alte (44) and poisoning by a caregiver (munchhausen by proxy) should be added to the differential diagnosis of these infants. moreover, urine drug screening tests should be considered in the evaluation (45). induced illness is a severe form of abuse that might cause death or permanent neurologic impairment. it might be accompanied by other severe abuse forms, which results in behavioral disorders. detection of this abuse requires a closed and focused collaboration of hospitals and community’s child health professionals, child psychiatrists, social workers, and police officers (46). bacterial infection serious bacterial infections (sbis) must be considered in all febrile infants with alte. the reported rates range from 0% to 8.2% and the possibility of bacteremia, meningitis, or urinary tract infection should be considered in infant presenting with an afebrile alte. the concern is greatest for infants younger than 60 days of age who might show few other symptoms to indicate the possibility of sbis (47). in patients with alte who appear well without suggestive signs of sbi, it might be possible to forego routine sepsis evaluation beyond a chest radiograph and urine culture without risking a serious missed diagnosis (42). routinely, children who present to the ed with alte do not need to undergo a full evaluation of sbi, while infants with such situation require infectious evaluation for sbi (48, 49). breath holding spells breath holding spells (bhs) are among the common benign paroxysmal nonepileptic disorders occurring in otherwise healthy children (50). the pathogenesis of bhs is not understood well, but some studies suggested that imbalance between the sympathetic and parasympathetic activity could play role in developing such a manifestation (51). the reported prevalence ranges from 0.1% to 4.6% in the general population (52). the diagnosis is usually made through description or observation of typical attacks characterized by a sequence of clinical events, beginning with a provoking event such as minor trauma or emotional upset, followed by a noiseless state of expiration accompanied by skin color change (paleness or cyanosis), and finally, loss of consciousness and postural tone (51). based on the skin color change during the attacks, bhs has two types: pallid and cyanotic; however, some children might experience mixed-type attacks (53). overall, the cyanotic type is more common and the ratio of cyanotic to pallid type is 3:1. although these attacks were previously considered as benign and self-limited in children between six and eight years of age, recent studies have shown that many of these patients would develop syncope attacks in the future (54). rarely, these spells might be an initial symptom of long qt syndromes or paroxysmal cardiac rhythm abnormalities (53). therefore obtaining an electrocardiogram to evaluate prolonged qt syndrome is strongly recommended. although bhs should be a diagnosis of exclusion in younger patients, some altes might present by early manifestations of bhs (54). management specific information that should be obtained in the history and physical examination is outlined in table 2 (54, 55). table 3 reviews the medications type and doses that might be required for the treatment of these patients, depending on their clinical picture (55-57). patients with alte can be easily categorized into one of the following three groups. the first group consists of those with clear diagnosis of alte obtained from the history or physical examinations. the second group included the infants without immediately clear diagnosis but appearing unstable. the third group, which is the largest, consists of well -appearing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 11 aminiahidashti emergency (2014); 2 (3): ***-*** infants with a concerning history, but their physical examinations show normal or noncontributory results. patients with a clear diagnosis altes are heterogeneous disorders that might frighten infants' caregivers (57). altes are not a diagnosis and therefore, the attention must be turn to find the underlying diseases (2). with a careful history review, physical examination, and some basic laboratory investigations, the main causes of alte might be discovered. invasive investigations like lumbar puncture (lp) should be reserved for ill patients or for those with laboratory or clinical impressions suggestive of central nervous system infections. clinicians should alarm the parents about recurrence of these episodes and train them on the primary life support activities as well as on avoiding any harmful reactions (58). after an alte work-up, hospitalization would be required if the etiology was life-threatening (57). unstable patients without a clear diagnosis for unstable patients without a clear diagnosis, the priority is stabilization, which requires assisted ventilation for infants with persistent compromised ventilation or those with frequent apnea requiring monitoring and stimulation in the ed. in such a situation, head injury, sepsis, metabolic or electrolyte disorder, poisoning, complicated table 2: important information of patient with apparent life-threatening event past medical history prematurity (birth before 37 weeks) prior hospitalization, surgery, or ed visits history of apnea prior respiratory difficulties (snoring or stridor) prior feeding difficulties (choking, gagging, or coughing with feeds) immunization status (pertussis) history of urinary tract infection family history history of sids or sudden death cardiac arrhythmias or congenital heart disease seizure disorder metabolic diseases event history duration of event (< 1 min, 1-5 min, or > 5 min) required resuscitation (e.g., stimulation, mouth-to-mouth breath, chest compressions) temporal relationship of feeding, sleeping, crying, vomiting, choking, or gagging skin color (cyanosis, pallor, or flushing) change in tone (including seizure activity, flaccid, or spastic) central vs. obstructive pattern of apnea (i.e., apparent respiratory effort) number of altes experienced within 24 h of presentation episodic vs. sustained change in mental status (syncope, postictal phase, irritability, or obtundation) correlation with feeding (at feeding time, few minute after feeding, or not related feeding) seasonal distribution (spring, summer, autumn, or winter) asleep or awake (awake, asleep, or both) position of the neonate (supine or prone) place of attack occurrence (parent's lap or cradle) review of systems respiratory symptoms or other intercurrent illness period of fasting (e.g. recent onset of sleeping through night) medication use, medications in the home or used by breastfeeding parent possible trauma social history possibility of follow-up comfort level of parents parental concern for abuse parental psychiatric issues or marital stress (e.g. absentee parent) exposure to the infectious agents (pertussis, rsv, upper respiratory infection, lower respiratory tract infection) alte, apparent life-threatening event; ed, emergency department; sids, sudden infant death syndrome; and rsv, respiratory syncytial virus. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (1): 8-15 12 no  careful history and physical examination  is this the first, short, self-correcting episode with feeding? ye s  examination is normal  parentral anxiety is addressed  ensure availability for follow-up yes are there any features that could be consistent with shaken baby? no  discharge  discuss the option of a home monitor with the family  review stimulation technique, cpr technique and sids risk factors  ensure follow-up no  admit  observation and cardiopulmonary monitoring for a minimum duration of 24 hours  is this history or examination point to a likely cause? yes initiate focused work-up and treatment plan based on the presumptive diagnosis  perform baseline investigations and check child protection register  full blood count and differential count, creactive protein, sodium, potassium, urea, calcium, magnesium, glucose, blood gas analysis, ammonia, lactate, pyruvate, and blood culture  urinalysis and culture  toxicology screen  freeze for metabolic studies if no other diagnosis was made  investigations for respiratory tract infection  ecg with measurement of qtc interval  investigation of gastroesophageal reflux  eeg  ultrasonography of brain yes is there any positive findings in head ct and skeletal survey study? yes no  treat underlying disease  involve child protective services no clear diagnosis severe or recurrent episode  observation  refer for invasive investigations no yes figure 1: investigation plan for an apparent life-threatening event this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 13 aminiahidashti emergency (2014); 2 (3): ***-*** pertussis, and bronchiolitis (in the neonate or expreemie) are the most likely causes (59). infants with alte should be investigated for the presence of respiratory pathogens, particularly bordetella pertussis and rsv. these infections might be accompanied by clinically undetected baseline and episodic hypoxemia (60, 61). stable patients without precise diagnosis in the clinical situation, when the patients with alte are considered to be idiopathic, some clinicians advocate a minimal evaluation with unexpansive tests for early detection of a rare, yet potentially devastating disease (e.g. infection or metabolic disease), to prevent long-term complications (62). this evaluation would include a complete blood count, c-reactive protein, basic metabolic panel, ammonia, lactate, pyruvate, blood gas measurement, urinalysis, toxicology screen, electrocardiogram, and microbiologic assessment for b. pertussis and rsv infections (62, 63). laboratory and paraclinical tests when the history includes an awake, supine infant fed in the last hour, gerd would be the most convincing diagnosis (64). in this case, a ph probe study is the best test although the nonacid reflux cannot be captured. although temporal association might be seen between acid reflux and symptoms, this test does not establish causality (65). a chest radiograph can be obtained, as indicated by history and physical examinations. while bacterial meningitis, sepsis, and urinary tract infections account for approximately 9% of the diagnoses, they should be considered in an ill-appearing infant (39). eeg had a 15% sensitivity for diagnosing epilepsy (66). some authors suggested that eeg should be taken from those with recurrent alte (63). some studies have reported the very high rates of cardiac arrhythmia including prolonged corrected qt interval, premature ventricular or atrial beats, or sinus node irregularity in full-term and otherwise healthy infants with previous altes who were undergone a 24-hour continuous holter monitoring (64). many metabolic conditions are triggered by fasting and might be accompanied by symptoms of hypotonia, lethargy, or vomiting. in these cases, laboratory evaluation including blood glucose, ph, ammonia, lactate, and pyruvic acid levels might help to find the underlying cause (2). it seems that performing lp is not necessary for all neonates with an episode of alte, especially those with normal findings on their physical exams. however, recommendation of lp might be reserved cases with high index of suspicion (13). if there is a suspicion of abuse or trauma, the evaluation should include ophthalmologic exam for retinal hemorrhage, head computed tomography (ct), and skeletal survey (67). disposition multiple possible etiologies and difficulties in evaluating and managing infants with alte pose a challenge for primary care physicians, emergency medicine specialists, and subspecialty pediatricians. the evaluation of these infants should include a detailed history, thorough physical examinations, and appropriate diagnostic tests based on the clues obtained from the patient's history and physical examinations (62). only 12% of infants referred to the ed with alte need a significant intervention warranting hospital admission (57). regarding infants with alte and no acutely ill appearance, there is no consensus on the minimal diagnostic evaluations and on the part of history and risk factors that should lead a practitioner toward admission to or discharge from the ed. clinical judgment remains a very important part of the decision-making process (68). a practical algorithm listed in figure1 (55, 57, 68). the alte term is nonspecific and describes a cluster of symptoms with many possible causes. in the clinical situation when the etiology of the alte is not established after a detailed history and comprehensive physical examination, which might be considered as idiotable 3: common intervention for ill patient with apparent life-threatening event indication medication/intervention dose/size hypoglycemia glucose 5-10 ml/kg of 10% dextrose in water, iv hyponatremia 3% normal saline 3-5 ml/kg bolus, iv hypocalcemia calcium 50-100 mg/kg calcium gluconate or 20 mg/kg calcium chloride, iv infection cefotaxime 50 mg/kg, iv ampicillin 50 mg/kg, iv anemia packed red blood cells 10 ml/kg, iv hypotension normal saline 20 ml/kg, iv metabolic disease 10% dextrose in one-fourth normal saline 1.5 maintenance (6 ml/kg/h for the first 10 kg) hypoventilation or frequent apnea endotracheal intubation 3.0 mm3 for preterm; 3.5 mm3 for term neonate; and 4.0 mm3 for older infant iv: intravenous; kg: kilogeram; ml: mililiter; h: houre; mm3: cubic millimeter this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (1): 8-15 14 pathic, some clinicians advocate a minimal diagnostic evaluation. the three following variables could identify most but not all of the infants with alte and necessitate admission: the obvious need for admission, significant medical history, and more than one alte episode during 24 hours. these variables require external validation and reliability assessment before clinical implementation (67). conclusion: children with alte referred to ed with anxious parents. several factors such as the number and type of alte manifestations, underlying diseases, and parents’ situation would affect the patient's management. the evaluation of these infants including detailed history, appropriate physical examination, and close observation in ed. further studies are recommended to identify the etiologic factors and appropriate management of children with alte. conflict of interest: none. funding support: none. references: 1. patricia king j. national institutes of health consensus development conference on infantile apnea and home monitoring, sept 29 to oct 1, 1986. pediatrics. 1987;79(2). 2. kahn a, european society for the s, prevention of infant d. recommended clinical evaluation of infants with an apparent life-threatening event. consensus document of the european society for the study and prevention of infant death, 2003. eur j pediatr. 2004;163(2):108-15. 3. edner a, wennborg m, alm b, lagercrantz h. why do alte infants not die in sids? acta paediatr. 2007;96(2):191-4. 4. kiechl-kohlendorfer u, hof d, peglow up, trawegerravanelli b, kiechl s. epidemiology of apparent life threatening events. arch dis child. 2005;90(3):297-300. 5. esani n, hodgman je, ehsani n, hoppenbrouwers t. apparent life-threatening events and sudden infant death syndrome: comparison of risk factors. j pediatr. 2008;152(3):365-70. 6. davies f, gupta r. apparent life threatening events in infants presenting to an emergency department. emerg med j. 2002;19(1):11-6. 7. stratton sj, taves a, lewis rj, clements h, henderson d, mccollough m. apparent life-threatening events in infants: high risk in the out-of-hospital environment. ann emerg med. 2004;43(6):711-7. 8. carroll jl. apparent life threatening event (alte) assessment. pediatr pulmonol suppl. 2004;26:108-9. 9. santiago-burruchaga m, sanchez-etxaniz j, benitofernandez j, et al. assessment and management of infants with apparent life-threatening events in the paediatric emergency department. eur j emerg med. 2008;15(4):203-8. 10. semmekrot ba, van sleuwen be, engelberts ac, et al. surveillance study of apparent life-threatening events (alte) in the netherlands. eur j pediatr. 2010;169(2):229-36. 11. brooks jg. apparent life-threatening events and apnea of infancy. clin perinatol. 1992;19(4):809-38. 12. md elias, vr iyer, cohen ms. prevalence of electrocardiogram use in infants with apparent lifethreatening events: a multicenter database study. pediatr emerg care. 2014;30(4):236–9. 13. brand da, altman rl, purtill k, edwards ks. yield of diagnostic testing in infants who have had an apparent lifethreatening event. pediatrics. 2005;115(4):885-93. 14. altman rl, brand da, forman s, et al. abusive head injury as a cause of apparent life-threatening events in infancy. arch pediatr adolesc med. 2003;157(10):1011-5. 15. doshi a, bernard-stover l, kuelbs c, castillo e, stucky e. apparent life-threatening event admissions and gastroesophageal reflux disease: the value of hospitalization. pediatr emerg care. 2012;28(1):17-21. 16. gray c, davies f, molyneux e. apparent life-threatening events presenting to a pediatric emergency department. pediatr emerg care. 1999;15(3):195-9. 17. romaneli mt, fraga am, morcillo am, tresoldi at, baracat ec. factors associated with infant death after apparent lifethreatening event (alte). j pediatr (rio j). 2010;86(6):515-9. 18. laisne c, rimet y, poujol a, et al. a propos de cent malaises du nourrisson. ann de pédiatrie. 1989;36(7):451-4. 19. hall kl, zalman b. evaluation and management of apparent life-threatening events in children. am fam physician. 2005;71(12):2301-8. 20. poets a, steinfeldt r, poets cf. sudden deaths and severe apparent life-threatening events in term infants within 24 hours of birth. pediatrics. 2011;127(4):e869-e73. 21. sarnat hb. myasthenia gravis. disorders of neuromuscular transmission and motor neurons. in: klieg man rm, behrman re, jenson hb, stanton bf, editors. nelson textbook of pediatrics. 18 ed. philadelphia: saunders; 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curr opin pediatr. 2007;19(3):288-94. 64. nunez j, cristofalo e, mcginley b, katz r, glen dr, gauda e. temporal association of polysomnographic cardiorespiratory events with ger detected by mii-ph probe in the premature infant at term. j pediatr gastroenterol nutr. 2011;52(5):52331. 65. tieder js, cowan ca, garrison mm, christakis da. variation in inpatient resource utilization and management of apparent life-threatening events. j pediatr. 2008;152(5):62935. e2. 66. vellody k, freeto jp, gage sl, collins n, gershan wm. clues that aid in the diagnosis of nonaccidental trauma presenting as an apparent life-threatening event. clin pediatr (phila). 2008. 67. kaji ah, claudius i, santillanes g, et al. apparent lifethreatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital. ann emerg med. 2013;61(4):379-87. 68. chu a, hageman jr. apparent life-threatening events in infancy. pediatr ann. 2013;42(2):78-83. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 38 emergency (2016); 4 (1): 38-40 casr report urinary retention and air in the spinal canal; a case report mohammadmahdi gheiratian, hoda karimian* department of emergency medicine, rasoul akram hospital, iran university of medical sciences, tehran, iran. *corresponding author hoda karimian; department of emergency medicine, rasoul akram hospital, niayesh st. sattarkhan ave. tehran, iran. tel: 0098(021)66525327. fax: 0098(021)66525327. e-mail: h_k_medicine@yahoo.com received: april 2015; accepted: june 2015 abstract cauda equina syndrome (ces) although uncommon, is a very serious condition, which should be diagnosed as soon as possible. urinary dysfunction following a lumbosacral trauma is a key for the physician to consider ces as the most probable diagnosis. up to 62% of ces patients report a recent episode of trauma. we herein report a young man with ces due to sacral fracture with an interesting imaging. key words: polyradiculopathy; lumbosacral region; spine; urinary retention. cite this article as: gheiratian mm, karimian h. urinary retention and air in the spinal canal; a case report. emergency. 2016;4(1):38-40 introduction: auda equina syndrome (ces) is a rare but highly impairing condition and is one of the few spinal surgical emergencies. this diagnosis refers to a complex of signs and symptoms resulting from compression of nerve roots distal to the conus medullaris. low back pain, motor weakness of lower limbs, sensory changes in saddle or perianal area, and loss of visceral function are some clinical manifestations of ces. however, we should keep in mind that clinical diagnosis of ces is made only when bladder, bowel, or sexual dysfunction and perianal or saddle numbness have occurred (1, 2). we herein report a young man with ces due to sacral fracture with an interesting imaging. case report: a 19-year-old afghan man was admitted to the emergency department (ed) because of urinary retention during the previous 24 hours. he was single and worked in a building as a laborer. he denied use of cigarettes, alcohol, and recreational drugs. in further investigation, he mentioned a trauma to his buttocks 3 to 4 days before, following a fall from an almost 3-meter height. he had been injured by a sharp material penetrating his right buttock. he had gone to a clinic and had his laceration sutured. on arrival to the c figure 1: axial computed tomography scan of sacrum shows bony fractured piece in the spinal canal. figure 2: axial computed tomography scan of sacrum shows air in the spinal canal, at level of sacral vertebrae. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 39 gheiratian and karimian ed, he did not complain of low back pain or sacral pain, saddle paresthesia, urinary or fecal incontinence, weakness of lower extremities, or any other symptoms. he had normal vital signs. in physical examination he had tenderness over sacrum, saddle hypoesthesia, and normal rectal tone. muscle forces of all limbs and deep tendon reflexes were normal and symmetric except for that of bilateral big toe extension and flexion which were 3/5 and 4/5 respectively. examination of the other parts did not reveal any positive findings. a foley catheter was fixed. lumbosacral computed tomography (ct) scan was performed, which showed sacral laminar fracture of s1, s2, and s3 with displacement of fractured bone forwardly to the spinal canal, and also air in the canal (figures 1, 2, and 3). lumbosacral magnetic resonance imaging (mri) demonstrated compression of cauda equina by bony pieces (figures 4 and 5). on the following day, he underwent sacral laminectomy of s1, s2, and s3, and fractured pieces were removed. in follow up, after almost 2 months he was completely symptom free with no complaint of urinary dysfunction or any other symptoms. discussion: urinary dysfunction following a lumbosacral trauma is a key for the physician to consider ces as the most probable diagnosis. as a matter of fact, once suspected, the physician should seek for trauma history, as up to 62% of patients report a recent episode of trauma (3, 4). likewise, our patient presented with chief complaint of urinary retention and retrospectively his trauma history was figured out. according to the literature, etiologies for ces are various and the most common ones include spinal trauma, herniated lumbar disk, neoplasms including metastases, and spinal infection/abscess (5-11). as mentioned earlier, the diagnosis of ces is based on bladder, bowel, or sexual dysfunction and perianal or saddle numbness. however, urinary dysfunction receives more attention because it shows itself sooner during the course of the disease compared to defecation dysfunction which develops slower or sexual dysfunction which only becomes apparent later, when the patient goes back to normal life (12). j. g. kennedy et al. established predictors of outcome in ces in a retrospective review of 19 patients with ces. they reported that there was a statistically significant correlation between delayed decompressions of greater than 24 hours and poor outcome such as presence of complete saddle anesthesia (13). although there is no clear agreement over the issue of timing of surgery in ces patients with true urinary retention, most authors are in favor of early decompression within the first 24 to 48 hours (11). conclusion: cauda equina syndrome, although uncommon, is a very serious condition, which should be diagnosed as soon as figure 3: axial computed tomography scan of lumbar spine shows air in the spinal canal at level of lumbar vertebrae. figure 4: sagittal t2 weighted magnetic resonance imaging shows compression of cauda equina by sacral fracture. figure 5: sagittal t1 weighted magnetic resonance imaging shows compression of cauda equina by sacral fracture. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 40 emergency (2016); 4 (1): 38-40 possible. once suspected, the physician should give special consideration to a detailed history about possible etiologies, and do a thorough physical exam. the symptoms are potentially reversible if surgical decompression is made in a timely manner. acknowledgments: the authors appreciate the insightful cooperation of emergency department staff of rasoul akram hospital. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. jensen rl. cauda equina syndrome as a postoperative complication of lumbar spine surgery. neurosurg focus. 2004;16(6):34-8. 2. motamedi m, baratloo a, majidi a, rahmati f, shahrami a. spontaneous spinal epidural hematoma; a case report. emergency. 2014;2(4):183-5. 3. ahn um, ahn nu, buchowski jm, garrett es, sieber an, kostuik jp. cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes. spine. 2000;25(12):1515-22. 4. hosseini m, karami z, janzadenh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. emergency. 2014;2(4):151-7. 5. kingwell sp, curt a, dvorak mf. factors affecting neurological outcome in traumatic conus medullaris and cauda equina injuries. neurosurg focus. 2008;25(5):e7. 6. raj d, coleman n. cauda equina syndrome secondary to lumbar disc herniation. acta orthopædica belgica. 2008;74(4):522. 7. bagley ca, gokaslan zl. cauda equina syndrome caused by primary and metastatic neoplasms. neurosurg focus. 2004;16(6):1-18. 8. gellido c, onesti s, llena j, suarez m. spinal schistosomiasis. neurology. 2000;54(2). 9. benzel ec, hadden ta, coleman je. civilian gunshot wounds to the spinal cord and cauda equina. neurosurgery. 1987;20(2):281-5. 10. aresti n, murugachandran g, shetty r. cauda equina syndrome following sacral fractures: a report of three cases. journal of orthopaedic surgery. 2012;20(2). 11. gitelman a, hishmeh s, morelli bn, et al. cauda equina syndrome: a comprehensive review. am j orthop. 2008;37(11):556-62. 12. tamburrelli f, genitiempo m, bochicchio m, donisi l, ratto c. cauda equina syndrome: evaluation of the clinical outcome. eur rev med pharmacol sci. 2014;18(7):1098-105. 13. kennedy j, soffe k, mcgrath a, stephens m, walsh m, mcmanus f. predictors of outcome in cauda equina syndrome. eur spine j. 1999;8(4):317-22. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 75 emergency (2015); 3 (2): 75-77 case report brachial artery aneurysm as a limb threatening condition; a case report farhad heydari, mehrsa taheri*, mehrdad esmailian 1department of emergency medicine, al-zahra hospital, isfahan university of medical sciences, isfahan, iran. *corresponding author: mehrsa taheri: department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran tel: 989133172474 ext 2082; email: mehrsa_taheri@yahoo.com received: october 2014; accepted: november 2014 abstract brachial artery aneurysms are rare but potentially limb threatening condition. the presented case here is a 52 year old male referred to the emergency department complaining a sudden onset and progressive pain with coldness of his right upper extremity during brushing. the right upper extremity was pulseless and three-dimensional computed tomography showed an aneurysm of the proximal right brachial artery associated with arterial occlusion in its distal branch. embolectomy was done, the aneurysm resected, and the artery successfully revascularised by interposing a saphenous vein graft. key words: brachial artery; aneurysm, dissecting; peripheral arterial disease; vascular grafting; limb salvage cite this article as: heydari f, taheri m, esmailian m. brachial artery aneurysm as a limb threatening condition; a case report. emergency. 2015;3(2):75-7. introduction: ocalized balloon-like bulge in an artery wall is called aneurysm that classified as true, pseudo, and mycotic types. true aneurysm is the localized dilation involving all three layers (intima, media, and adventitia) of the arterial wall, but a false type o r pseudoaneurysm is a collection of flowing blood that communicates with the arterial lumen and is filled only by the adventitia or surrounding soft tissue (1). aneurysms can manifest in all arteries but peripheral artery aneurysms in the upper extremities are rare so that brachial artery aneurysms have an overall prevalence of 0.5% (2-4). also, mycotic and post-traumatic are more common than true aneurysm (3, 5). there are few reports in this regard and the following presentation described a patient referred to the emergency department (ed) with signs and symptoms of arterial insufficiency and final diagnosis of brachial artery aneurysm. case report: a 52-year-old male referred to the ed with complaining of sudden onset and progressive pain with coldness of his right upper extremity when he was brushing. the subject had no other complaint such as chest pain, palpitation, or shortness of breathing. he had no history of trauma, injection, dialysis, arteriography, intravenous drug abuse, or surgery in his right upper extremity. the patient’s history was negative regarding hypertension, ischemic heart diseases, diabetes mellitus, hyperlipidemia, etc. on physical examination, he had a swelling on his right axilla without pigmentation. palpation revealed a 2 × 2.5 centimetre pulsatile, compressible mass with no tenderness and the temperature equal to the surrounding skin. supraclavicular and axillary lymph nodes were not bilaterally palpable. pulse of the axillary artery was palpable, but brachial and radial arteries were pulseless. the capillary refill time was in normal range and sensory and motor functions were intact. cardiac examination revealed no murmurs, lungs sounded clear, and abdomen was soft with no tenderness. the remainder of the systemic examination was unremarkable. paraclinic investigation showed 6800/mm3 white blood cell (wbc) count , 14gram/decilitre haemoglobin level, 13 millimetres/hour erythrocyte sedimentation rate (esr), 13 seconds prothrombin time (pt), and 33 seconds partial thromboplastin time (ptt). color doppler ultrasonography of right upper extremity arteries showed an anechoic, pulsatile, 25 × 22 millimetres mass with turbulent flow seen along the brachial artery. computed tomoangiography showed an aneurysm of the proximal right brachial artery associated with arterial occlusion in distal radial branch (figures 1 and 2). embolectomy was done, the aneurysm resected, and the brachial artery successfully re-vascularised by interposing a saphenous vein graft. the resected aneurysm displayed a true aneurismal sac filled with internal thrombus. finally, the patient was discharged, under warfarin anticoagulation therapy, without any complication on the fifth days after surgery. l this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com heydari et al 76 figure 1: computed tomoangiography of the proximal right brachial artery (axial cuts). figure 2: three-dimensional computed tomoangiography of the proximal right brachial artery, white arrow shows the location of aneurysm. discussion: the usual manifestation of peripheral aneurism is incidentally finding of a pulsatile, painless and asymptomatic mass, which becomes symptomatic when complications arise. thrombosis in the sac, vascular collapse which throws emboli into peripheral circulation, and also disruption caused the profuse bleeding are among these complications (5). atherosclerotic aneurysms, which commonly develop in advanced ages, are often seen in large arteries, while pseudoaneurysm may be observed in any location and age. aneurysms are generally revealed in infrequent locations due to marfan’s syndrome, syphilis, and major trauma. familial history of aneurysm, connective tissue disorders, and atherosclerotic risk factors (hypertension, hyperlipidemia, smoking, and age) are considered as it’s risk factors (1, 4, 6). without proper management, hemorrhage, extremity venous edema, cutaneous erosion, and especially adjacent neurological structure compression can develop due to enlargement of the aneurysm. the first symptom of upper extremity aneurysms can be nerve injury due to adjacent nerve compression (2). prompt diagnosis and treatment of true peripheral artery aneurysms are necessary to minimize the complication rate and serious long-term squeal (7, 8). differential diagnosis include pulsating tumours (such as bone sarcoma, osteoclastoma), arterio-venous malformation, lymphadenopathy, lipoma, hematoma, and abscess. the diagnosis should be confirmed by a duplex ultrasonography, show the arterial blood flow into the aneurysm. computed tomography or magnetic resonance angiography can also be used for diagnosis (9). in spite of all above-mentioned, the gold standard tool is a selective upper extremity arteriography. however, the first choices in investigation are often color doppler ultrasonography and subtraction image angiography (2). the defect in the artery is usually small and easily identified by a transient release of the proximal clamp (5). close observation, thrombin injection, ultrasound-guided compression, and operative repair are treatment options. conclusion: aneurysms of the brachial artery are not common, but could be potentially limb threatening. prompt diagnosis and proper treatment may prevent from irreversible squeal. the best therapeutic option is immediate operative repair. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of al-zahra hospital. conflict of interest: none funding support: none this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 77 emergency (2014); 3 (2): 75-77 authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. hall ha, minc s, babrowski t. peripheral artery aneurysm. surgical clinics of north america. 2013;93(4):911-23. 2. yetkin u, gurbuz a. post-traumatic pseudoaneurysm of the brachial artery and its surgical treatment. texas heart institute journal. 2003;30(4):293. 3. bahcivan m, yuksel a. idiopathic true brachial artery aneurysm in a nine-month infant. interactive cardiovascular and thoracic surgery. 2009;8(1):162-3. 4. clarke m, waterland p, bahia s, asquith j, pherwani a, wong j. true brachial artery aneurysm: a rarity. ejves extra. 2012;23(4):e27-e8. 5. tetik o, ozcem b, orgen calli a, gurbuz a. true brachial artery aneurysm. texas heart institute journal. 2010;37(5):618. 6. fann ji, wyatt j, frazier rl, cahill jl. symptomatic brachial artery aneurysm in a child. journal of pediatric surgery. 1994;29(12):1521-3. 7. schunn cd, sullivan tm. brachial arteriomegaly and true aneurysmal degeneration: case report and literature review. vascular medicine. 2002;7(1):25-7. 8. ghazi ma, khan am, akram y, cheema ma. brachial artery aneurysm. japan medical association journal. 2006;49(4):173. 9. kouvelos gn, papas nk, arnaoutoglou em, papadopoulos gs, matsagκas mi. endovascular repair of profunda femoral artery false aneurysms using covered stents. vascular. 2011;19(1):51-4. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 159 emergency (2015); 3 (4): 159-161 brief repert prevalence of tramadol consumption in first seizure patients; a one-year cross-sectional study payman asadi, vahid monsef kasmaei, seyyed zia ziabari, behzad zohrevandi*, aslan moadab manesh road trauma research center, guilan university of medical sciences, rasht, iran. *corresponding author: behzad zohrevandi; road trauma research center, guilan university of medical sciences, rasht, iran. tel: 09188523847. fax: +981313238373; email: bzohrevandi@yahoo.com received: april 2015; accepted: may 2016 abstract introduction: previous studies have shown that there is a probability of seizure even with therapeutic doses of tramadol. yet, no accurate data exist regarding this problem in iran. therefore, the present study aimed to evaluate the prevalence of tramadol consumption in patients with first seizure referred to the emergency department (ed). methods: in the present retrospective one-year cross-sectional study, all patients who were referred to the ed of poursina hospital, rasht, iran, with the complaint of first seizure were evaluated. demographic data and data regarding history of tramadol consumption, duration, total dose, last dose, and time passed from the last dose of consumption were recorded and analyzed regarding the study questions using spss 20. results: 383 (68.9%) out of the 556 patients referred to the ed, were experiencing their first seizure (mean age 26.43 ± 6.48 years; 70.5% male). 84 (21.9%) patients had recently used tramadol. history of seizure in the family of tramadol consumers was significantly lower (3.6% compared to 11%; p = 0.036). mean total tramadol consumption dose in the last 24 hours was 140.17 ± 73.53 mg (range: 50-300 mg). duration of tramadol consumption was less than 10 days in 84.5% (df: 2; χ2 = 96.1; p < 0.001). in addition, 62 (73.8%) patients had seizure within 6 hours of consumption (df: 3; χ2 = 29.5; p < 0.001). conclusion: results of the present study showed that 21.9% of the patients with first seizure had a history of tramadol consumption. seizure following tramadol consumption is more prevalent in the initial 10 days and within 6 hours of consumption. in addition, it seems that lower doses of tramadol may also induce seizure. key words: seizures; tramadol; prevalence; epidemiology cite this article as: asadi p, monsef kasmaei v, ziabari sz, zohrevandi b, moadab manesh a. prevalence of tramadol consumption in first seizure patients; a one-year cross-sectional study. emergency. 2015;3(4):159-61. introduction: ramadol is an opioid used for treating moderate to severe pain. it has been legally used for pain management since 1980 in some countries, and has been approved by food and drug administration of iran since 2003. this drug is addictive and may be abused by the youth. nausea, vomiting, central nervous system depression, tachycardia, cardiorespiratory arrest, and seizure are among the side effects of tramadol poisoning. however, there are reports that indicate the probability of seizure induction even with therapeutic doses of this drug (1-5). tramadol abuse is increasing in iran, (2, 6) and seizure is possible among abusers. therefore, the present study aimed to evaluate the prevalence of tramadol abuse in patients with first seizure, who were referred to the emergency department (ed). methods: in the present retrospective cross-sectional one-year study, all first seizure patients referred to the ed of poursina hospital, rasht, iran, during 2012 were evaluated. for each patient, data regarding age, sex, history of seizure in family, recent history of tramadol consumption, duration (days), total dose, last dose, and time passed from the last dose of consumption were recorded using a checklist. data were then analyzed using spss 20.0. quantitative data were reported as mean ± sd and qualitative ones as frequency and percentage. the groups with and without recent tramadol consumption were compared using independent t-test for quantitative variables and chi square or fisher’s exact test for qualitative ones. in addition, multinomial logistic regression test was used to evaluate distribution of the patients in groups regarding age, sex, duration of consumption, consumed dose in the last 24 hours, and time passed from the last dose of tramadol consumption. in all analyses, p < 0.05 was considered as significance level. this study t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com asadi et al 160 was approved by the ethics committee of guilan university of medical sciences. the researchers adhered to the principles of helsinki declaration. results: 383 (68.9%) out of the 556 patients who were referred to the ed with chief complaint of seizure throughout the course of the study, were experiencing their first seizure. mean age of first seizure patients was 26.43 ± 6.48 years (range: 16-55 years; 70.5% male). 84 (21.9%) patients out of the 383 first seizures had recent history of tramadol consumption. 69 (82.1%) of tramadol consumers and 201 (67.2%) of other patients were male (p = 0.005). 48.8% of the tramadol consuming patients and 59.9% of other patients were 20 -30 years old (p = 0.016). history of seizure in the famil y of tramadol consumers was significantly lower (3.6% compared to 11%; p = 0.036). table 1 shows baseline characteristics of the tramadol consumers. mean total tramadol consumption dose in the last 24 hours was 140.17 ± 73.53 mg (range: 50-300 mg). duration of consumption was less than 10 days in 84.5% of the patients, 11-20 days in 10.7%, and more than 20 days in 4.8%. incidence of seizure following ingestion was higher in patients who had recently started consumption (df: 2; χ2 = 96.1; p < 0.001). yet, no correlation was detected between tramadol dosage and seizure incidence (df: 3; χ2 = 1.2; p = 0.1). seizure had occurred within 6 hours of consumption in 62 (73.8%) patients (df: 3; χ2 = 29.5; p < 0.001). discussion: findings of the present study showed that 68.9% of the patients referred to poursina hospital, rasht, iran, were experiencing their first seizure, 21.9% of which had recent history of tramadol consumption. seizure following tramadol consumption was more prevalent in the initial 10 days and within 6 hours of consumption. previous studies show that about 86% of neurologic side effects manifest within 6 hours of consumption (7, 8). the present study showed that 73.8% of seizures due to tramadol consumption also happened in this time. based on the existing standards, to prevent side effects such as seizure, daily dose of tramadol should not exceed 400 mg (1, 2, 9). in this cross-section, mean total tramadol consumption dose in 24 hours was 140.17 ± 73.53 mg. in a study by shadnia et al. (2), this dose was 1650 mg while, in a study by pedramfar et al. (5), total dose in the 12 hours pre-seizure was 363.2 ± 303.1 mg (50 -1500). mean consumption dose in the participants of this study was significantly lower than the mentioned studies. this may be due to the patients not revealing their real consumption dose, genetic differences in the studied populations, different pharmaceutical companies making the drugs and other unknown reasons. therefore, we should note that tramadol might also be able to induce seizure in lower doses. one of the limitations of this study was being retrospective, which led to limited access to some table 1: baseline characteristics of tramadol consuming patients characteristics number (%) p value sex male 69 (82.1) ref female 15 (17.9) <0.001 age (year) < 20 19 (22.7) 0.006 20-30 41 (48.8) ref 31-40 18 (21.4) 0.004 > 40 6 (7.1) <0.001 consumption duration (day) < 10 71 (84.5) ref 11-20 9 (10.7) <0.001 > 20 4 (4.8) <0.001 dose in the last 24 hours (mg) 50 16 (19.0) ref 50-100 27 (32.1) 0.1 100-200 29 (34.5) 0.06 > 200 12 (14.3) 0.45 time passed since the last dose (hour) < 3 hours 32 (38.1) ref 3-6 hours 30 (35.7) 0.8 6-12 hours 18 (21.4) 0.049 > 12 hours 4 (4.8) <0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 161 emergency (2015); 3 (4): 159-161 of the required data. moreover, serum tramadol level was not evaluated and therefore its correlation with seizure incidence could not be determined. conclusion: results of the present study showed that 21.9% of the patients with first seizure had a history of tramadol consumption. seizure following tramadol consumption is more prevalent in the initial 10 days and within 6 hours of consumption. although the maximum recommended therapeutic dose of tramadol is 400 mg/day, mean consumption dose among the participants of this study was 140.17 ± 53.73 mg. therefore, we might be able to conclude that lower doses of tramadol may also induce seizure. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. mehrpour m. intravenous tramadol-induced seizure: two case reports. iran j pharmacol therapeut. 2005;4(2):146-7. 2. shadnia s, soltaninejad k, heydari k, sasanian g, abdollahi m. tramadol intoxication: a review of 114 cases. hum exp toxicol. 2008;27:201–5. 3. derakhshanfar h, kalantari meibodi m, kariman h, arhamidolatabadi a, safari s. substance abuse among drivers of motor vehicle collisions. trauma mon. 2012;2012(01, apr):236-8. 4. tashakori a, afshari r. tramadol overdose as a cause of serotonin syndrome: a case series. clin toxicol (phila). 2010;48(4):337-41. 5. pedramfar p, borhani haghighi a. tramadol induced seizure: report of 106 patients. iran red crescent med j. 2010;12(1):49-51. 6. hassanian moghaddam h, pajoumand a. a oneyear epidemiological study of acute poisoning among adults and adolescents admitted to loghman hospital, tehran between 2005 and 2006. pajouhandeh. 2007;12(57):169-76. [persian]. 7. jovanovic-cupic v, martinovic z, nešic n. seizures associated with intoxication and abuse of tramadol. clin toxicol. 2006;44(2):143-6. 8. marquardt ka, alsop ja, albertson te. tramadol exposures reported to statewide poison control system. ann pharmacother. 2005;39(6):1039-44. 9. baratloo a, rouhipour a, forouzanfar m, rahmati f, hashemi b. hypokalemia-induced abnormal movements: case report. trauma mon. 2013;18(3):141-5. introduction: methods: results: discussion: conclusion: conflict of interest: funding support: authors’ contributions: references: emergency 2016; 4 (4): 196-201 or i g i n a l re s e a rc h validation of crash model in prediction of 14-day mortality and 6-month unfavorable outcome of head trauma patients behrooz hashemi1, mahnaz amanat1∗, alireza baratloo1, mohammad mehdi forouzanfar1, farhad rahmati1, maryam motamedi1, saeed safari1 1. clinical research developmental center, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2015; accepted: september 2015 abstract: introduction: to date, many prognostic models have been proposed to predict the outcome of patients with traumatic brain injuries. external validation of these models in different populations is of great importance for their generalization. the present study was designed, aiming to determine the value of crash prognostic model in prediction of 14-day mortality (14-dm) and 6-month unfavorable outcome (6-muo) of patients with traumatic brain injury. methods: in the present prospective diagnostic test study, calibration and discrimination of crash model were evaluated in head trauma patients referred to the emergency department. variables required for calculating crash expected risks (er), and observed 14-dm and 6-muo were gathered. then er of 14-dm and 6-muo were calculated. the patients were followed for 6 months and their 14-dm and 6-muo were recorded. finally, the correlation of crash er and the observed outcome of the patients was evaluated. the data were analyzed using stata version 11.0. results: in this study, 323 patients with the mean age of 34.0 âś 19.4 years were evaluated (87.3% male). calibration of the basic and ct models in prediction of 14-day and 6-month outcome were in the desirable range (p < 0.05). area under the curve in the basic model for prediction of 14-dm and 6-muo were 0.92 (95% ci: 0.89–0.96) and 0.92 (95% ci: 0.90–0.95), respectively. in addition, area under the curve in the ct model for prediction of 14-dm and 6-muo were 0.93 (95% ci: 0.91–0.97) and 0.93 (95% ci: 0.91–0.96), respectively. there was no significant difference between the discriminations of the two models in prediction of 14-dm (p = 0.11) and 6-muo (p = 0.1). conclusion: the results of the present study showed that crash prediction model has proper discrimination and calibration in predicting 14-dm and 6-muo of head trauma patients. since there was no difference between the values of the basic and ct models, using the basic model is recommended to simplify the risk calculations. keywords: prognosis; head injuries, closed; multiple trauma; patient outcome assessment; decision support techniques. © copyright (2016) shahid beheshti university of medical sciences cite this article as: hashemi b, amanat m, baratloo a, forouzanfar m, rahmati f, motamedi m, safari s. validation of crash model in prediction of 14-day mortality and 6-month unfavorable outcome of head trauma patients. 2016; 4(4):196-201. 1. introduction t rauma is the third cause of mortality in developed countries and the most common cause of death in people under 40 years old (1, 2). statistics show that iran is among the countries with the highest incidence of road traffic accidents worldwide with more than 21000 traffic-related deaths annually. in iran, accidents are the sec∗corresponding author: mahnaz amanat; emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran; telephone: +989128251535; email: mah.amanat@yahoo.com. ond cause of mortality and the most important one for hospitalization (3, 4). based on the existing reports, about 70% of mortality and disabilities caused by accidents are due to head trauma (5, 6). evaluations done in the united states indicate that every year 150–200 out of each million people are affected with severe physical and mental disabilities due to traumatic brain injuries (7, 8). physicians believe that accurate evaluation of prognosis is a very important, yet difficult task (9, 10). to date, many prognostic models have been proposed to predict the outcome of patients with traumatic brain injuries, but none have been widely used (11– 13). crash (corticosteroid randomization after significant head injury) prognostic model is one of them, which has this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com mah.amanat@yahoo.com 197 emergency 2016; 4 (4): 197-201 been developed in recent years and has two separate outcome prediction models for high and low-middle income countries. crash model has been proposed by medical research council during crash trial project with a sample size greater than 10000. the model claims to be able to predict 14-day mortality (14-dm) and 6-month unfavorable outcome (6-muo) of head trauma patients (14). although discrimination and external validation of this model have been evaluated in multiple studies, the results have been contradicting (15–19). therefore, the present study was designed, aiming to determine the value of crash prognostic model in prediction of 14-dm and 6-muo of patients with traumatic brain injury. 2. methods in the present prospective diagnostic test study, head trauma patients referred to imam hossein and shohadaye tajrish hospitals, tehran, iran, from 2012 to 2014 were evaluated. using census sampling, all the head trauma patients (isolated or multiple trauma) who were referred to the emergency department (ed) within 8 hours of trauma with a gcs (glasgow coma scale) ≤ 14 were included. patients with missing follow-up data or not willing to participate were excluded. initially, a senior emergency medicine resident gathered the variables required for calculating crash expected risks (er), and observed 14-dm and 6-muo. then er regarding 14-dm and 6-muo were calculated for both computed tomography (ct) scan and basic models (4 scores for each patient) using the web based calculator. the patients were subject to follow-up for 6 months and their 14-dm and 6-muo were gathered and recorded. finally, the correlation of crash er and the observed outcome of the patients was evaluated. the present study was approved by the ethics committee of shahid beheshti university of medical sciences. researchers adhered to the principles of helsinki declaration over the course of the study and before being included in the study, informed written consent form was signed by the patient or their relatives. 2.1. definition of crash model this model reports the er of 14-dm and 6-muo of head trauma patients as percentage. it has a basic model for low and middle-income countries that predicts the outcome without the need for head imaging and a ct model for highincome countries based on head imaging findings (14). data needed in the basic model consists of age, level of consciousness based on gcs, pupil reactivity, and presence of major extracranial injury. the ct model needs brain ct scan findings in addition to the 4 mentioned factors in the basic model (14). in the two models, 6-month outcome is determined based on glasgow outcome scale (gos). therefore, the patients are divided into 2 groups of 6-month favorable (good recovery or moderate disability) and unfavorable (severe disability, vegetative state, and death) outcome. 2.2. statistical analyses the data were analyzed using stata version 11.0. qualitative factors were reported as frequency and percentage, and quantitative ones as mean and standard deviation. in the present study, discrimination and calibration were used on the data for evaluation of model performance. discriminatory power of the model was evaluated using the area under the receiver operating characteristic (roc) curve and calculation of likelihood ratio. area under the roc curve in the basic and ct models were compared to identify the best model. best cut-off points for classifying patients into low, moderate, and high-risk groups were determined. in addition, calibration of model was assessed using logistic regression analysis and calculation of intercept, and slope of the line. the er line was then compared with the observed one using hosmerlemeshow test. the non-significant result of this test means that there is a correlation between the expected outcomes by the model and those observed in reality, a representative of proper calibration. in all analyses, p < 0.05 was considered as significance level. 3. results 3.1. demographic out of the 403 patients entering the study, 80 (19.85%) were excluded because of missing follow-up data (80.14% followup rate). in the present study 323 patients with the mean age of 34.0 ± 19.4 years (1–90 years) were evaluated (87.3% male). table 1 shows demographic characteristics of the participants. 65.3% of the patients were referred to the hospital within an hour of the accident. road traffic collision with 58.8% prevalence and falling down with 28.8% were the most important mechanisms of injury. in total, 64 (19.8%) patients died in the 14-day and 7 (2.2%) in the 6-month follow up. in addition, 10 (3.1%) patients had severe disability in the 6month follow up. 3.2. calibration of model figure 1 (a and b) shows the calibration curve of ct and basic models. slope of the regression line in basic and ct models in prediction of 14-dm were 1.1 (p = 0.07) and 1.3 (p = 0.065), respectively. in addition, these slopes were 1.05 (p = 0.15) and 1.23 (p = 0.065) respectively for 6-month outcome of the patients (figure 1, c and d). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com hashemi et al. 198 table 1: baseline characteristics of the studied population variable number (%) age < 20 62 (20.2) 20-29 81 (26.5) 30-39 52 (17.0) 40-49 44 (14.4) 50-59 26 (8.5) ≤ 60 41 (13.4) gender male 282 (87.3) female 41 (12.7) time since injury (hour) <1 211 (65.3) 1-3 82(24.4) >3 30(9.3) mechanism of trauma road traffic collision 190(58.8) falling down> 2 meters 93 (28.8) other 40 (12.4) glasgow coma scale mild (14-15) 130 (40.5) moderate(9-13) 112 (34.9) severe(3-8) 79 (24.6) pupil reaction to light stimulation none 32 (9.9) one side 30 (9.3) both side 261 (80.8) major extracranial injuries yes 70 (21.7) no 253 (78.3) computed tomography scan petechial hemorrhage yes 126 (39.0) no 197 (61.0) obliteration of the third ventricle or basal cisterns yes 15 (4.6) no 308 (95.4) subarachnoid hemorrhage yes 77 (23.8) no 246 (76.2) midline shift yes 33 (10.2) no 290 (89.8) non-evacuated hematoma yes 215 (66.6) no 108 (33.4) 4. discriminatory power 4.1. basic models the mean er of 14-dm was 46.3 ± 28.16% in those who died and 7.78 ± 10.3% in those who survived based on this model (p < 0.001). in addition, mean er of 6-muo were 41.56±13.46% and 17.9±19.3% for observed unfavorable and favorable outcome groups, respectively (p < 0.001). area under the roc curve in prediction of 14-dm and 6-muo were 0.92 (95% ci: 0.89–0.96) and 0.92 (95% ci: 0.90–0.95), respectively (figure 2). based on the calculated likelihood ratio the patients with < 3.9%, 3.9–63.89%, and ≥ 64% er of 14-dm were in the observed low, moderate, and high risk groups, respectively. in addition, patients with < 18%, 18–43.19%, and ≥ 43.2% er of 6-muo were in the observed low, moderate, and high risk groups, respectively (tables 2 and 3). 4.2. ct model the mean er of 14-dm was 44.0 ± 26.2% in those who died and 7.9 ± 8.9% in the survivors (p < 0.001), based on ct model. in addition, mean er of 6-muo were 45.9±16.5% and 20.6±19.3% for observed unfavorable and favorable outcome groups, respectively (p < 0.001). area under the roc curve in the ct model in prediction of 14-dm and 6-muo were 0.93 (95% ci: 0.91–0.97) and 0.93 (95% ci: 0.91–0.96), respectively (figure 2). based on the calculated likelihood ratio the patients with < 4.7%, 4.7–51.19%, ≥ 51.2% er of 14-dm were in the observed low, moderate, and high risk groups, respectively. in addition, patients with < 17.8%, 17.8–78.69%, and ≥ 78.7% er of 6-muo were in the observed low, moderate, and high risk groups, respectively (table 2 and 3). 5. discussion the results of the present study showed that crash model has proper discrimination and calibration in predicting 14dm and 6-muo of the patients referred to the ed with head trauma. calculation of likelihood ratio showed that patients with an er of < 3.9% in the basic model are at low risk for mortality in 14 days, while those with ≥ 63.9% are at high risk. these cut-off points are 4.7% and 51.2%, respectively for the ct model. in addition, when the er of 6-month outcome is < 17.8% in the ct model and < 18 in the basic one, observation of unfavorable outcome is very unlikely. on the other hand, if er of 6-muo is > 43.19 in basic and > 78.69 in ct model, observation of unfavorable outcome is very likely. the present study confirmed the proper value of crash models in predicting the outcome of head trauma patients. this result is in line with the crash trial study from which the model was extracted (14). wong et al. also expressed that calibration and discrimination of crash model are desirable for predicting 14-day outcome. they also added that crash model shows a mild underestimation in predicting 6-month outcome (19). majdan et al. also showed that the crash model has a good ability in predicting patients outcome but it shows underestimation in prediction of 6-month outcome (17). in contrast, honeybul et al. believed that crash model overestimated the 6-month outcome, especially when the er was < 80% (15). these dissimilarities might be due to different mechanisms of trauma. on the other hand, the definition of major extracranial injury in the majdan et al. study is difthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 199 emergency 2016; 4 (4): 199-201 (a) (b) (c) (d) figure 1: calibration of basic and computed tomography (ct) scan model in prediction of 14-day mortality (a and b) and 6-month unfavorable outcome (c and d). ferent from the present study and the crash trial. although the population that crash model was extracted from consisted of people over 16 years old (14), children were also included in this study. even though 36 (11.1%) of the patients were under 16 years old, calibration and discrimination of the crash model was desirable in predicting the outcome of head trauma patients. in sub group analysis, area under the roc curve was calculated to be 0.95 (95% ci: 0.88– 1.0) in the basic model and 0.96 (95% ci: 0.92–1.0) in the ct model in prediction of 14-dm of those under 16 years of age. they were 0.95 (95% ci: 0.90–1.0) and 0.96 (95% ci: 0.91– 1.0), respectively in prediction of their 6-muo. the findings reported here were obtained by studying only 36 children and teenagers; therefore, further studies and more data are needed to confirm the predictive value of this model in them. previous studies report that complex models that contain accurate data and diagnostic tests such as ct scan, have better discrimination in predicting patient outcome (16, 18). however, the present study showed that the ct model does not provide better calibration or discrimination compared to the basic model. in line with these findings, majdan et al. also showed that ct models have no advantage over basic models in predicting patient outcome (17). therefore, it seems that the basic model has appropriate power for predicting outcomes without needing ct scan results. one of the limitations of the crash trial is lack of an accurate definition for some prognostic factors in the crash dataset. for example, the definition for extracranial injury covers a very wide range, which includes all the cases that need hospitalization. this general and somehow unclear definition leads to alteration of the er based on the decision of the physician. this is the reason that majdan et al. defined extracranial injury as abbreviated injury scale > 2 in their study. however, the researchers of the present study used the definitions of the crash trial to ensure minimum alterations from the original study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com hashemi et al. 200 (a) (b) figure 2: area under the receiver operating characteristics curve (auc) of basic and computed tomography (ct) scan models in prediction of 14-day mortality (a) and 6-month unfavorable outcome (b). table 2: risk stratification of 14-day mortality in head trauma patients based on crash model expected risk (er) outcome likelihood ratio p survived died basic model low risk (er < 3.9) 146 (100) 0 (0.0) 0.0∗ <0.0001moderate risk (3.9 ≥ er < 63.9) 111 (73.5) 40 (26.5) — high risk (er ≥ 63.9) 1 (38.0) 25 (96.2) 99.2† ct model low risk (er < 4.7) 144 (100) 0(0.0) 0.0∗ <0.0001moderate risk (4.7 ≥ er < 51.2) 113(73.9) 40 (26.1) high risk (er ≥ 51.2) 2 (7.7) 24 (92.3) 47.6† ∗ negative likelihood ratio. † positive likelihood ratio. 6. conclusion the results of the present study showed that crash model has proper discrimination and calibration in predicting 14dm and 6-muo of the head trauma patients. since there was no difference between the values of the basic and ct models, using the basic model is recommended to simplify the risk calculations. 7. appendix 7.1. acknowledgement the authors wish to thank the staff of emergency department of imam hossein and shohadaye tajrish hospitals for their valuable contribution in data gathering. 7.2. author contribution behrooz hashemi and saeed safari designed the study method and analyzed the data. mahnaz amanat, maryam motamedi, and farhad rahmati gathered the data. alireza baratloo and mohammad mehdi forouzanfar contributed in study design and data gathering. all authors have contribution in drafting and writing the article and accept responsibility for all parts of the study. 7.3. funding and support there is no source of funds or financial support in the present study. 7.4. conflict of interest none references 1. bruns j, hauser wa. the epidemiology of traumatic brain injury: a review. epilepsia. 2003; 44(s10): 2–10. 2. kumar a, lalwani s, agrawal d, rautji r, dogra t. fatal road traffic accidents and their relationship with head inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 201 emergency 2016; 4 (4): 201-201 table 3: risk stratification of 6-months unfavorable outcome in head trauma based on crash model expected risk (er) outcome likelihood ratio p survived died basic model low risk (er < 18.0) 174 (100) 0 (0.0) 0.0∗ <0.0001moderate risk (18.0 ≥ er < 43.2) 46 (75.4) 15 (24.6) — high risk (er ≥ 43.2) 25 (28.4) 63 (71.6) 7.5† ct model low risk (er < 17.8) 166 (100) 0(0.0) 0.0∗ <0.0001moderate risk (17.8 ≥ er < 78.7) 74(60.2) 49 (39.8) high risk (er ≥ 78.7) 4 (11.8) 30 (88.2) 23.9† ∗ negative likelihood ratio. † positive likelihood ratio. juries: an epidemiological survey of five years. the indian journal of neurotrauma. 2008; 5(2): 63–7. 3. montazeri a. road-traffic-related mortality in iran: a descriptive study. public health. 2004; 118(2): 110–3. 4. majdzadeh r, khalagi k, naraghi k, motevalian a, eshraghian mr. determinants of traffic injuries in drivers and motorcyclists involved in an accident: accident analysis & prevention. 2008; 40(1): 17–23. 5. bigler ed, weiner m, lipton a. traumatic brain injury. textbook of alzheimer disease and other dementias. 2009: 229–46. 6. ghajar j. traumatic brain injury. the lancet. 2000; 356(9233): 923–9. 7. maegele m, engel d, bouillon b, lefering r, fach h, raum m, et al. incidence and outcome of traumatic brain injury in an urban area in western europe over 10 years. european surgical research. 2007; 39(6): 372–9. 8. thurman dj, alverson c, dunn ka, guerrero j, sniezek je. traumatic brain injury in the united states: a public health perspective. the journal of head trauma rehabilitation. 1999; 14(6): 602–15. 9. kövesdi e, lückl j, bukovics p, farkas o, pál j, czeiter e, et al. update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics. acta neurochirurgica. 2010; 152(1): 1–17. 10. maas ai, marmarou a, murray gd, teasdale sgm, steyerberg ew. prognosis and clinical trial design in traumatic brain injury: the impact study. journal of neurotrauma. 2007; 24(2): 232–8. 11. menon d, harrison d. prognostic modelling in traumatic brain injury. bmj. 2008; 336(7641): 397–8. 12. steyerberg ew, mushkudiani n, perel p, butcher i, lu j, mchugh gs, et al. predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. plos medicine. 2008; 5(8): e165. 13. young nh, andrews pj. developing a prognostic model for traumatic brain injury–a missed opportunity? plos medicine. 2008;5(8):e168. 14. collaborators mct, perel p, arango m, clayton t, edwards p, komolafe e, et al. predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. bmj. 2008; 336(7641): 425–9. 15. honeybul s, ho km, lind cr, gillett gr. observed versus predicted outcome for decompressive craniectomy: a population-based study. journal of neurotrauma. 2010; 27(7): 1225–32. 16. lingsma h, andriessen tm, haitsema i, horn j, van der naalt j, franschman g, et al. prognosis in moderate and severe traumatic brain injury: external validation of the impact models and the role of extracranial injuries. journal of trauma and acute care surgery. 2013; 74(2): 639–46. 17. majdan m, lingsma hf, nieboer d, mauritz w, rusnak m, steyerberg ew. performance of impact, crash and nijmegen models in predicting six month outcome of patients with severe or moderate tbi: an external validation study. scandinavian journal of trauma, resuscitation and emergency medicine. 2014; 22(1): 68. 18. roozenbeek b, lingsma hf, lecky fe, lu j, weir j, butcher i, et al. prediction of outcome after moderate and severe traumatic brain injury: external validation of the impact and crash prognostic models. critical care medicine. 2012; 40(5): 1609–17. 19. wong gkc, teoh j, yeung j, chan e, siu e, woo p, et al. outcomes of traumatic brain injury in hong kong: validation with the triss, crash, and impact models. journal of clinical neuroscience. 2013; 20(12): 1693–6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discriminatory power discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 21 emergency (2016); 4 (1): 21-24 original research an epidemiologic study of pediatric poisoning; a six-month cross-sectional study mohammad manouchehrifar1, niloufar derakhshandeh2, majid shojaee3, anita sabzghabaei1, fariba farnaghi2* 1. department of emergency, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of pediatrics, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: fariba farnaghi; department of pediatrics, loghman hakim hospital, makhsous avenue, tehran, iran. tel: +989125865182 email: faribafarnaghi@yahoo.com received: april 2015; accepted: may 2015 abstract introduction: intentional and unintentional poisoning are among the most common reasons for referrals to emergency department (ed). therefore, the present study was designed to evaluate epidemiologic features and effective risk factors of intentional and unintentional poisoning in children. methods: this prospective cross-sectional study was carried out in ed of loghman hakim hospital, greatest referral poison center of iran, tehran during march to august 2014. demographic data, medical history, history of psychiatric disease in child, the cause of poisoning, parents’ educational level, household monthly income, location of residence, history of addiction or divorce in family, and the poisoning intentionality were gathered. data were analyzed using spss 18 and appropriate statistical tests based on the purpose of study. results: 414 participants with the mean age of 4.2 ± 3.43 years were included (57.5% male). children in the 0-4 year(s) age range had the most frequency with 281 (67.9%) cases. 29 (7%) cases were intentional (62% female, 76% in the 10-14 years old group). methadone with 123 (29.7%) cases was the most frequent toxic agent in general and in unintentional cases. 10-14 years of age (p = 0.001), and the history of psychiatric disease in children (p <0.001), had a direct correlation with probability of intentional poisoning. while, history of addiction in the family showed an indirect correlation with this probability (p = 0.045). conclusion: based on the results of this study, most cases of poisoning in the children were unintentional methadone intoxication in boys in the 0-4 age range with a history of a psychiatric disease, and those who had a history of addiction in the family. in addition, the most powerful risk factor for the children’s intentional poisoning was their history of psychiatric disease. the history of addiction in the child’s family had indirect correlation with intentional intoxications. key words: poisoning; child, hospitalized; mental disorders; methadone; suicide cite this article as: farnaghi f, manouchehrifar m, shojaee m, sabzghabaei a, derakhshandeh n. an epidemiologic study of pediatric poisoning; a six-month cross-sectional study. emergency. 2016;4(1):21-24. introduction: ntentional and unintentional poisoning are among the most common reasons for referrals to emergency department (ed) (1). intentional cases are responsible for more than 60% of related deaths (2). following car accidents, poisoning is the second frequent cause of child death due to unintentional harm (3). unintentional poisoning occurs more in children as a result of their curiosity and wanting to copy their parents (4). although the frequency of hospitalization due to intentional harm is decreasing among children and teenagers in recent decades, it is still a challenge for the health systems (5). based on previous reports, teenagers make up 22% of the poisoned patients referred to eds in iran, which is considerable in comparison to european countries (6). outcomes such as death and hospitalization in intensive care unit (icu) have psychological and financial consequences for the person, their family, and society. therefore, the present study was designed to evaluate epidemiologic features and effective risk factors of intentional and unintentional poisoning in children. methods: this prospective cross-sectional study was carried out in ed of loghman hakim hospital, greatest referral poison center of iran, tehran during march to august 2014. children and teenagers aged 0-14 year(s) old who were referred to the ed due to poisoning were included. the patients’ data were gathered using a checklist that consisted of demographic data, medical history, history of psychiatric disease in child, the cause of poisoning, level i this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com farnaghi et al 22 of education, household’s monthly income, location of residence, history of addiction or divorce in family, and intentionality. the ethics committee of shahid beheshti university of medical sciences approved the protocol of this study and all researchers were committed to keeping the patients’ data confidential based on the recommendations of helsinki declaration. parents of all participants signed the informed written consent form. statistical analysis spss 18 was used for data analysis. quantitative data were reported as mean ± standard deviation and qualitative data as frequency and percentage. chi square test was used to evaluate the relationship between variables. then a stepwise logistic regression was designed to identify independent effective factors on occurrence of poisoning. in all the tests, p < 0.05 was considered as significance level. results: 414 participants with the mean age of 4.2 ± 3.43 years were included (57.5% male). children 0-4 year(s) old had the most frequent age category with 281 (67.9%) cases. 260 (63%) cases of poisoning was seen in children who resided in downtown. 29 (7%) cases were intentional, 62% female and 76% in the 10-14 years old group. table 1 summarizes the demographic data of the patients and figure 1 shows the frequency of the toxic agents based on intentionality of poisoning. methadone with 123 (29.7%) cases was the most frequent toxic agent in general and in unintentional cases. benzodiazepines with 17.24% (5 cases) prevalence were the most common toxic agent in intentional cases. among probable risk factors, 10 to 14 years of age (p < 0.001), female gender (p = 0.023), history of addiction in the child’s family (p = 0.003), history of psychiatric disease in the child (p < 0.001) and type of toxic agent (p < 0.001) had significant correlation with poisoning incidence. table 2 shows the results of stepwise logistic regression analysis. based on this analysis, out of the five mentioned factors 10-14 years of age (p = 0.001) and history of psychiatric disease (p < 0.001) had a direct correlation with table 1: baseline characteristics of the studied patients characteristics type of harm frequency (%) p-value intentional unintentional age groups (year) 0-4 2 (0.7) 279 (99.3) <0.001 5-9 5 (6.7) 70 (93.3) 10-14 22 (42.3) 30 (57.7) gender male 11 (4.6) 227 (95.4) 0.02 female 18 (10.2) 158 (89.8) history of psychiatric disease positive 23 (71.9) 9 (28.1) <0.001 negative 5 (1.8) 273 (98.2) history of illness positive 0 (0) 23 (100) 0.18 negative 29 (7.5) 356 (92.5) history of addiction in family positive 4 (2.3) 169 (97.7) 0.003 negative 14 (10.4) 120 (89.6) history of divorce in family positive 1 (50) 1 (50) 0.14 negative 28 (6.8) 384 (93.2) location of residence south (downtown) 17 (6.5) 243 (93.5) west 2 (3.6) 53 (96.4) 0.38 east 4 (8.5) 43 (91.5) north 6 (12) 44 (80) father’s level of education high school diploma or less 27 (7.6) 327 (92.4) 0.25 associate degree or above 2 (3.8) 50 (96.2) mother’s level of education high school diploma or less 24 (7.2) 308 (92.8) 0.56 associate degree or above 5 (6.8) 69 (93.2) family’s monthly income 400 dollars or less 24 (7.3) 306 (92.7) 400-800 dollars 5 (7.9) 58 (92.1) 0.61 800 dollars or more 0 (0) 12 (100) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 23 emergency (2016); 4 (1): 21-24 probability of intentional poisoning. while, history of addiction in the family showed an indirect correlation with this probability (p = 0.045). 5 (1.2%) cases of intentional poisoning and 13 (3.1%, 53.8% female) cases of unintentional ones needed intensive care, but none of the cases died. discussion: based on the results of the present study, most cases of poisoning in the studied children were in the 0-4 age range, male, children with a history of psychiatric disease, and those who had a history of addiction in the family. in addition, 90% of the poisoning cases were unintentional and occurred due to consuming methadone. acute poisoning is a life-threatening condition and epidemiologic evaluations in this field and detecting its predisposing risk factors, especially in children, can be a research priority. a study in 2012, has estimated the prevalence of unintentional poisoning to be 49 cases in 10,000 children (7). regarding gender distribution, the results of the present study was similar to previous studies in south africa and canada, but not to the one from texas, united states of america (8-10). additionally, most cases of poisoning were seen in the 0-4 age range and most prevalence of intentional poisoning was observed in the 10-14 age range. while, in a similar study in canada most poisoning was detected in children under 1 year old and over 15 (10). the high percentage of unintentional poisoning, especially in the 0-4 year(s) group, can be due to their curiosity and tendency to copy their parents. a comprehensive study on 11674 poisoned children, expressed that the prevalence of unintentional cases was 5 times the intentional ones (11). in the studied population, the most frequent type of poisoning was drug intoxication, like the previous studies, which can be due to their availability (5, 12-15). in most studies analgesics and psychotherapeutic agents were the most commonly used drugs (6, 8, 12-14). whereas, in this study methadone was the most common toxic agent. methadone is an analgesic synthetic opioid and the high prevalence of intoxication with it, detected in this study, could be due to careless storage of this toxic drug, especially in families undergoing methadone therapy for rehabilitation. in this study, the probability of intentional poisoning was higher in children with a history of psychiatric disease such as depression, behavioral disorders and hyperactivity. a study in iran, expressed that 47% of the suicide cases in children were related to history of psychiatric disease in the children or their family (16). in children with a history of addiction in their family, odds of intentional poisoning was lower, compared to others. the reason might be less referral of these cases figure 1: frequency of toxic agents based on intentional or unintentional poisoning (p < 0.001). table 2: results of stepwise logistic regression analysis p z odds ratio (95% confidence interval) factors 0.001 3.39 1.45 (1.17-1.79) age (10-14 years) 0.47 0.72 1.76 (0.37-8.22) female gender <0.001 4.01 35.77 (6.21-205.88) history of psychiatric disease 0.045 -2.01 0.13 (0.01-0.95) history of addiction in family 0.53 0.63 1.4 (0.75-1.74) toxic agent 0% 20% 40% 60% 80% 100% methadone opiums banzodiazepines other hydrocarbons stimulant ageants anti-psychotic agents organophosphorus nsaids anti-hypertensive agents anti-histamine agents multi-drug ingestion non intentional intentional this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com farnaghi et al 24 to the hospital by the family, more prevalence of unintentional poisoning, and lower level of knowledge in these families. educational programs and professional social work with the aim of teaching life skills to the patients and their families can widely prevent or reduce the risk of poisoning. the limitations of this study include restricted access to patients’ medical history and low level of parent’s cooperation. conclusion: based on the results of this study, most cases of poisoning in the children were unintentional methadone intoxication in boys in the 0-4 age range with a history of a psychiatric disease, and those who had a history of addiction in the family. in addition, the most powerful risk factor for the children’s intentional poisoning was their history of psychiatric disease. the history of addiction in the child’s family had indirect correlation with intentional intoxications. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency and pediatrics department of loghman hakim hospitals, tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. lipnik-štangelj m. hospitalizations due to poisonings in slovenia–epidemiological aspects. wien klin wochenschr. 2010;122(2):54-8. 2. krenzelok ep. the use of poison prevention and education strategies to enhance the awareness of the poison information center and to prevent accidental pediatric poisonings. clin toxicol. 1995;33(6):663-7. 3. mohammadi n, karbakhsh m, pajoumand a. epidemiologic aspects of deliberate self-poisoning in adolescents: a hospitalbased study in tehran. tehran uni med j. 2007;65(4):59-64. [persian]. 4. sawalha af, sweileh wm, tufaha mt, al-jabi dy. analysis of the pattern of acute poisoning in patients admitted to a governmental hospital in palestine. basic clin pharmacol toxicol. 2010;107(5):914-8. 5. olfson m, gameroff mj, marcus sc, greenberg t, shaffer d. national trends in hospitalization of youth with intentional self-inflicted injuries. am j psychiatry. 2005;162(7):1328-35. 6. sarjami s, pajoumand a. one year epidemiological study of acute adult and adolescent poisoning admitted to loghman hospital, tehran, 2004-2005. sci j forensic med. 2008;13(48):235-40. 7. monuteaux mc, lee l, fleegler e. children injured by violence in the united states: emergency department utilization, 2000–2008. acad emerg med. 2012;19(5):535-40. 8. ramisetty-mikler s, mains d, rene a. poisoning hospitalizations among texas adolescents: age and gender differences in intentional and unintentional injury. tex med. 2005;101(5):64-71. 9. herbert hk, van as ab, bachani am, et al. patterns of pediatric injury in south africa: an analysis of hospital data between 1997 and 2006. j trauma acute care surg. 2012;73(1):168-74. 10. avdimiretz n, phillips l, bratu i. focus on pediatric intentional trauma. j trauma acute care surg. 2012;72(4):1031-4. 11. limbos map, peek-asa c. comparing unintentional and intentional injuries in a school setting. j sch health. 2003;73(3):101-6. 12. marahatta s, singh j, shrestha r, koju r. poisoning cases attending emergency department in dhulikhel hospitalkathmandu university teaching hospital. kathmandu uni med j. 2009;7(2):152-6. 13. paulozzi lj, ryan gw. opioid analgesics and rates of fatal drug poisoning in the united states. am j prev med. 2006;31(6):506-11. 14. prosser jm, perrone j, pines jm. the epidemiology of intentional non-fatal self-harm poisoning in the united states: 2001–2004. j med toxicol. 2007;3(1):20-4. 15. cox s, kuo c, jamieson dj, et al. poisoning hospitalisations among reproductive-aged women in the usa, 1998–2006. inj prev. 2011;17(5):332-7. 16. mehdizadeh m, zamani g, kabiri m. attempt to suicide in children in loghman hospital. iran j pediatr. 2006;16(3):33742. emergency. 2016; 4 (3): 163-165 ca s e re p o rt erythema multiforme as a result of orf disease; a case report tahmine biazar1, mehran shokri1, hajar hosseinnia2, masomeh bayani1∗ 1. infectious diseases and tropical medicine research center, babol university of medical sciences, babol, iran. 2. clinical research development unit, rouhani hospital, babol university of medical science. babol, iran. received: february 2016; accepted: march 2016 abstract: orf is a mucocutaneous disease that occurs when non-intact skin comes into contact with contaminated sheep saliva. the lesions may complicate to lymphangitis or secondary bacterial infection, but systemic complications such as erythema multiforme, maculopapular rash, and generalized lymphadenopathy are rare. in this paper, we present two cases of erythema multiforme following orf disease. keywords: orf virus; erythema multiforme; emergency department; infectious disease medicine © copyright (2016) shahid beheshti university of medical sciences cite this article as: biazar t, shokri m, hosseinnia m, bayani m. erythema multiforme as a result of orf disease; a case report. emergency. 2016; 4(3):163-165. 1. introduction orf is a mucocutaneous disease caused by double-stranded dna parapoxviruses that is also known as sheep pox, ecthyma contagiosum, and contagious pustular dermatitis (13). human transmission occurs when non-intact skin comes into contact with contaminated sheep and goat saliva and their dead body (4). the incubation period varies from 3 to 10 days and then single or multiple lesions evolve, which arise mostly in the hands and face. at the onset of disease, primary lesions are the papules that gradually progress to nodular patterns. the nodules change into tubercule or crusted form within 4-6 weeks (5). the lesions may complicate to lymphangitis or secondary bacterial infection but systemic complications such as erythema multiforme, maculopapular rash, and generalized lymphadenopathy are rare (6, 7). in this paper, we present two cases of erythema multiforme following orf disease. 2. case report 2.1. case 1 a 45-year-old woman was admitted to the emergency department with chief complaint of generalized erythema, low∗corresponding author: masomeh bayani; infectious diseases and tropical medicine research center, babol university of medical sciences, babol, iran. tel:+989113112559; e-mail:m_baiany@yahoo.com. grade fever, and mild itching. she had a history of hypertension and captopril consumption from 3 years ago. on arrival, vital signs were stable and only a low fever was detected. on physical examination, disseminated maculopapular rash and target lesions in favor of erythema multiforme were seen. moreover, there were several purple nodules with a brief fluctuation in the proximal phalange of right index finger and distal phalange of third right finger (figure 1). finger lesions appeared 5 days after contact with a sheep and gradually enlarged during the 25 days before present complaint. laboratory data showed mild leukocytosis. based on clinical features, history of contact with sheep, and the high prevalence of disease in mazandaran province, iran, diagnosis of orf disease was made with a high pretest probability for finger lesions, which is complicated to erythema multiforme. patient was treated with warm compress, and low dose of intravenous corticosteroid and antihistamine. the generalized eruptions disappeared within five days with complete recovery after 6 weeks. 2.2. case 2 the second case was a 32-year-old woman admitted to the emergency department with generalized maculopapular rash, low fever and sore throat. she had a negative medical and drug history. on arrival, vital signs were stable and physical examination revealed papulopustular lesions on first phalange of right thumb and generalized maculopapular rash with target lesions (figure 2). patient remembered exposure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e-mail: m_baiany@yahoo.com biazar et al. 164 figure 1: skin lesions of case 1. figure 2: skin lesions of case 2. to the head of a sheep several days ago. same as the first presented case, erythema multiforme following orf disease was diagnosed and supportive therapy with low doses of intravenous corticosteroid and antihistamine was administered. the systemic eruptions were cured within 6 days and orf lesions disappeared after 5 weeks. 3. discussion orf or pustular dermatitis or milker’s nodule is a disease caused by parapaxvirus transmitted to humans via contact with infected goat and sheep (8). the disease occurs most frequently on the fingers, hands and face. after an incubation period of 4-6 days, an erythematous papule appears and possibly goes to nodular and pustular form (9). milker’s nodule can complicate to fever, lymphangitis, lymphadenopathy or bacterial super-infection. rare complications of the disease are vesioculo-pustular eruptions such as erythema multiforme (9, 10). these reactions are considered to be an immune response to the orf infection (10). differential diagnoses include pyoderma, herpetic whitlow, cowpox, cat-scratch disease, anthrax, tularemia, tuberculosis, other mycobacteria, syphilis, sportrichosis, keratoacanthoma, and pyogenic granuloma (10). diagnosis of orf is usually based on clinical findings and history of exposure of non-intact skin to contaminated sheep and goat saliva and their dead body. virus isolation, tissue culture and polymerase chain reaction (pcr) in some cases could be helpful but they are expensive and difficult (9, 10). orf is a self-limiting disease and is completely resolved in about 4-6 weeks (2, 10). conservative therapy and local antiseptic to prevent bacterial supperinfection are recommend, but for large lesions cryotherapy or topical cidofovir cream could be used (2, 11). low dose systemic steroid and antihistamines are useful in treatment of erythema multiforme (12). orf disease should be considered as a possible underlying cause of erythema multiforme in endemic area. 4. appendix 4.1. acknowledgements we express our thanks to all staff at rohani hospital, babol, iran for their help and assistance in management of these cases. 4.2. author’s contributions all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 4.3. funding and support none. 4.4. conflict of interest none. references 1. haig dm, mercer a. ovine diseases. orf. veterinary research. 1997;29(3-4):311-26. 2. alian s, ahangarkani f, arabsheybani s. a case of orf disease complicated with erythema multiforme and bullous pemphigoid-like eruptions. case reports in infectious diseases. 2015;2015. 3. odom rb, james wd, berger tg. andrews’ diseases of the skin: clinical dermatology: wb saunders philadelphia, pa; 2000. 4. lo c, mathisen g. human orf in los angeles county. western journal of medicine. 1996;164(1):77. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 165 emergency. 2016; 4 (3): 165-165 5. unal g, gundes s, ustun m. human orf: echtyma contagiosum report of five cases. turkish journal of medical sciences. 2002;32(2):173-5. 6. coskun o, gul ch, bilgeturk a, besirbellioglu ba, eyigun cp. human orf complicated with erythema multiforme. international journal of dermatology. 2008;47(12):13334. 7. assier h, bastuji-garin s, revuz j, roujeau j-c. erythema multiforme with mucous membrane involvement and stevens-johnson syndrome are clinically different disorders with distinct causes. archives of dermatology. 1995;131(5):539-43. 8. slattery wr, juckett m, agger wa, radi ca, mitchell t, striker r. milkers’ nodules complicated by erythema multiforme and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation for multiple myeloma. clinical infectious diseases. 2005;40(7):e63-e6. 9. ozturk p, sayar h, karakas t, akman y. erythema multiforme as a result of orf disease. acta dermatovenerologica alpina, pannonica, et adriatica. 2011;21(2):45-6. 10. joseph r, haddad f, matthews a, maroufi a, monroe b, reynolds m. erythema multiforme after orf virus infection: a report of two cases and literature review. epidemiology and infection. 2015;143(02):385-90. 11. azizzadeh m. orf followed by erythema multiforme (case report). 2007. 12. lamoreux mr, sternbach mr, hsu wt. erythema multiforme. am fam physician. 2006;74(11):1883-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion appendix references archives of academic emergency medicine. 2023; 11(1): e27 rev i ew art i c l e prognostic value of crash and impact models for predicting mortality and unfavorable outcome in traumatic brain injury; a systematic review and meta-analysis hamed zarei1, mohammadhossein vazirizadeh-mahabadi1, hamzah adel ramawad2, arash sarveazad3,4∗, mahmoud yousefifard1,5 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. department of emergency medicine, nyc health & amp; hospitals, coney island, new york. 3. colorectal research center, iran university of medical sciences, tehran, iran. 4. nursing care research center, iran university of medical sciences, tehran, iran. 5. pediatrics chronic kidney disease research center, tehran university of medical sciences, tehran, iran. received: december 2022; accepted: january 2023; published online: 4 march 2023 abstract: introduction: the corticosteroid randomization after significant head injury (crash) and the international mission for prognosis and analysis of clinical trials (impact) are two prognostic models frequently used in predicting the outcome of patients with traumatic brain injury. there are ongoing debates about which of the two models has a better prognostic value. this study aims to compare the crash and impact in predicting mortality and unfavorable outcome of patients with traumatic brain injury. method: we performed a literature search using medline (via pubmed), embase, scopus, and web of science databases until august 17, 2022. after two independent researchers screened the articles, we included all the original articles comparing the prognostic value of impact and crash models in patients with traumatic brain injury. the outcomes evaluated were mortality and unfavorable outcome. the data of the included articles were analyzed using stata 17.0 statistical program, and we reported an odds ratio (or) with a 95% confidence interval (95% ci) for comparison. results: we included the data from 16 studies. the analysis showed that the areas under the curve of the impact core model and crash basic model do not differ in predicting the mortality of patients (or=0.99; p=0.905) and their six-month unfavorable outcome (or=1.01; p=0.719). additionally, the crash ct model showed no difference from the impact extended (or=0.98; p=0.507) and impact lab (or=1.00; p=0.298) models in predicting the mortality of patients with traumatic brain injury. we also observed similar findings in the six-month unfavorable outcome, showing that the crash ct model does not differ from the impact extended (or=1.00; p=0.990) and impact lab (or=1.00; p=0.570) in predicting the unfavorable outcome in head trauma patients. conclusion: low to very low level of evidence shows that impact and crash models have similar values in predicting mortality and unfavorable outcome in patients with traumatic brain injury. since the discriminative power of the impact core and crash basic models is not different from the impact extended, impact lab, and crash ct models, it may be possible to only use the core and basic models in examining the prognosis of patients with traumatic injuries to the brain. keywords:brain injuries, traumatic; prognosis; survival analysis; mortality; patient outcome assessment cite this article as: zarei h, vazirizadeh-mahabadi m, adel ramawad h, sarveazad a, yousefifard m. prognostic value of crash and impact models for predicting mortality and unfavorable outcome in traumatic brain injury; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e27. https://doi.org/10.22037/aaem.v11i1.1885. ∗corresponding author: arash sarveazad, colorectal research center, rassol-e-akram hospital, nyayesh st. sattarkhan st., tehran, iran. email: arashsarveazad@gmail.com. orcid: https://orcid.org/0000-0002-7947-8642. † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, tehran, iran. email: yousefifard20@gmail.com. orcid: https://orcid.org/0000-0002-7947-8642. 1. introduction traumatic brain injury (tbi) is a significant cause of morbidity and mortality worldwide. it is one of the most common complications of intentional and unintentional accidents, with a global prevalence of 8.4%. based on existing reports, the incidence and prevalence of tbi due to head trauma have significantly risen since the 1990s (1). this presents a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 2 unique challenge for hospitals because available healthcare resources are likely to become overburdened by higher rates of tbi. physicians can identify intracranial injuries from head traumas through imaging modalities such as computed tomography (ct) scan and magnetic resonance imaging (mri). however, there are challenges to imaging trauma patients suspected of tbi. while scanning patients has become essential for trauma diagnostic work-up, not all hospitals are equipped with ct machines or technicians. other challenges include the deterioration of hemodynamically unstable patients in the radiology suite and high exposure to ionizing radiation (2, 3). as a result, healthcare providers are researching different tests and measures to diagnose tbi, especially in patients unable to undergo head imaging. the glasgow coma scale (gcs) measures the level of consciousness in a person following trauma and classifies tbi as mild, moderate, and severe. despite several clinical decision rules to help identify clinically significant head injuries, physicians continue to face the challenge of deciding who needs a brain ct while minimizing unnecessary radiation exposure. while minor head injury is commonly seen in the emergency department, investigators have found that only 16% of these patients will have an acute intracranial lesion (4). this means that if every patient with mild head injury was to undergo cerebral imaging, 84% of these studies would be normal and unnecessary. to reduce unnecessary imaging and waste of hospital resources, a prognostic scoring system can be helpful. although multiple prognostic models for predicting mortality and disability following traumatic brain injuries exist, none are widely used in clinical practice. most of these models are limited based on small population size and lack external validation. most models were designed based on data from developed countries, which are not clinically practical to the majority of head trauma and accidents that occur in developing countries (5, 6). the corticosteroid randomization after significant head injury (crash) model is one of the best prognostic tools for tbi, designed in recent years. it has two separate outcome prediction models for high and low-middle income countries. as a result, the crash model can be applied to different populations unlike other prognostic models. designed by the medical research council (mrc) with a sample size of more than 10,000 people, the crash model predicts 14-day mortality and 6-month unfavorable outcome (7). although this model’s discrimination and external validation have been evaluated in several studies (8-12), the findings have been contradictory. another prediction model for patients with tbi, which has received more attention recently, is the international mission for prognosis and analysis of clinical trials in tbi (impact) (11). this model also aims to predict the outcome of mortality and unfavorable outcome for patients with tbi. crash and impact are the most externally validated models for predicting mortality and unfavorable outcome in tbi patients. many studies have evaluated both models and confirmed their validity. in a study by de cássia almeida vieira et al., results show that both models have a similar prognostic value in predicting mortality and unfavorable outcome in severe tbi (13). however, there is still a difference of opinion regarding which of these models works better for predicting the outcome of brain injuries. therefore, we aim to compare the value of these two prognostic models, crash and impact, in predicting mortality and unfavorable outcome of head trauma patients. 2. methods 2.1. study design the present study is a systematic review and meta-analysis to compare the value of the two prognostic models of crash and impact in predicting mortality and unfavorable outcome of patients with traumatic brain injury. for this purpose, we thoroughly searched the available databases and electronic resources to find all articles related to the topic of our study. this study was designed based on the guidelines for meta-analysis of observational studies. the searching and summarizing data method has been reported in the previous meta-analyses of the researchers of this study (2, 1423). here, we explain a summary of the activities carried out to achieve the goals of this study. 2.2. description of pico the description of pico in the present study is as follows: the problem or study population (p): human studies conducted on brain trauma patients targeted intervention (i): predictive value of crash and impact models comparisons (c): comparison with the survival group or favorable outcome outcome (o): mortality and unfavorable outcome are the primary outcomes of this study 2.3. search strategy in the current research, we selected the keywords using three strategies: medline database mesh and embase database emtree, experts’ opinions in the field, and the review of keywords and the titles of related articles. then, using an appropriate combination of these keywords, an extensive search was conducted in the electronic databases of medline (via pubmed), embase, scopus, and web of science until august 17, 2022. we presented the medline search strategy in appendix 1. in addition to the systematic search, we performed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e27 figure 1: flow diagram for selection of studies. a manual search in the google search engine, google scholar, and related article sources. 2.4. eligibility criteria inclusion criteria in the current study, we included the human studies conducted to investigate the prognostic value of crash and impact models in predicting mortality and unfavorable outcomes of traumatic brain injury. the research population is human studies without age, sex, and race restrictions. exclusion criteria failure to compare crash and impact prognostic models simultaneously in one study, studies conducted on children, failure to report injury outcomes, failure to report assessment method, and review articles were the study’s exclusion criteria. 2.5. data extraction after removing duplicate articles from the systematic search results, two independent researchers performed the initial screening by reading the title and abstract of the articles. the full text of the relevant articles was examined in detail. we included the studies in the present systematic review based on the inclusion and exclusion criteria. we resolved any disagreements through discussion with a third researcher. the extracted data includes information related to the study design, sample characteristics (age, gender), number of examined samples, the severity of tbi, the interval between the injury and evaluation of impact and crash prognostic models, duration of follow-up, and quality assessment of selected articles. in cases where the data could not be extracted from the article, we contacted the authors of the article. if the corresponding author did not respond to the first email, two follow-up emails were sent (with an interval of one week). in cases of no responses, other article authors were contacted through professional social platforms such as research gate and linkedin to provide the required information to the researchers. 2.6. quality assessment of the studies the quality of the studies was determined using the quadas-2 guidelines (24). to evaluate the agreement between the two researchers, we investigated the inter-rater reliability in the quality assessment of the studies. in case of disagreements, we resolved the difference through discussion with the third researcher. 2.7. the level of evidence the level of evidence was evaluated based on the grading of recommendations assessment, development and evaluation (grade) framework (25). since all the studies included in this study were observational, the base score of these articles starts from the low level based on the grade guide. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 4 in the presence of a large magnitude of effect, dose-response gradient, and plausible confounders, the score of the level of evidence could be increased between 1 and 3 points. 2.8. statistical analyses we performed the analyses in stata 17.0. all studies were summarized and divided based on their outcome and predictive value. all included studies reported the area under the curve for the impact and crash models with a 95% confidence interval. therefore, we calculated a pooled area under the curve (auc) with a 95% confidence interval (95% ci). impact model has three types: impact core model, impact extended model, and impact lab model. impact core model is calculated based on clinical findings. impact extended model is calculated based on clinical findings and ct scan investigations (core model + ct scan). impact lab model includes clinical findings, ct scan, and blood glucose and hemoglobin level (core model + ct scan + laboratory assessment). the crash model also includes two models, basic and ct. the basic model is based on clinical findings, and the ct model requires ct scan findings in addition to clinical findings. therefore, to compare the impact and crash prognostic models’ areas under the curve, we compared the impact core and crash basic models together, and the impact extended, impact lab, and crash ct models together. finally, the odds ratio (or) was checked with a 95% confidence interval by performing a meta-regression to determine which model has the best prognostic performance. we used the random effect model in the present study due to the existence of heterogeneity. to check heterogeneity between studies, we used the i2 test. using egger’s test method, funnel plot was used to identify publication bias (26). 3. results 3.1. studies’ characteristics the search resulted in 2174 articles. after removing duplicates, we included 1156 studies in our initial screening process. after examining the title and abstract of the included articles, we read 66 of them in detail. the data of 16 studies were included in the final analysis (27-42). these studies included the data of 39,829 patients with suspected traumatic brain injury. the reasons for the exclusion of articles from the present study included failure to examine the prognostic value of impact and crash models simultaneously (29 articles), failure to report the required data (9 articles), review studies (4 articles), studies conducted on pediatric population (2 articles) and non-related studies (6 articles). one study had not reported the auc with 95% confidence interval, so we contacted the authors twice but received no response; therefore, this study was also excluded (43). details on the number of studies excluded during selection for metaanalysis are provided in figure 1. the interval between the occurrence of brain injury and the investigation of impact and crash models varied between 12 to 48 hours. the sampling method was prospective in 10 studies, retrospective in 5, and amphi-directional in 1. the severity of tbi ranges from mild to severe. the follow-up period was 180 days in 12 studies, 14 days in 1 study, and 540 days in 1 study. two studies followed the patients until discharge from the hospital (table 1). 3.2. quality assessment and publication bias we assessed the risk of bias based on the quadas-2 tool (table 2). the risk of bias was high in three studies in the patient selection domain and unclear in six studies in the flow and timing domain. in other domains, all studies had a low risk of bias. we checked the publication bias for the prognostic value of impact and crash models in predicting mortality and unfavorable outcome. the analysis showed that in investigating the prognostic value of the impact core model (p=0.045) and impact extended model (p=0.021) in predicting the unfavorable outcome, there is evidence of publication bias (figure s1 and figure s2). in other scores, there was no publication bias in predicting mortality or unfavorable outcome. 3.3. comparing the predictive values for mortality crash basic and impact core model the analyzes showed that the auc of the crash basic and impact core models in predicting the mortality of head trauma patients are 0.82 (95% ci: 0.77 to 0.86) and 0.80 (95% ci: 0.77 to 0.84), respectively (figure 2). these two models have no difference in predicting the patients’ mortality (diagnostic or=0.98; 95% ci: 0.93 to 1.04; p=0.550). crash ct, impact extended, and impact lab the analyzes showed that the auc in the crash ct, impact extended, and impact lab models in predicting the mortality of head trauma patients are 0.80 (95% ci: 0.74 to 0.86), 0.81 (95% ci: 0.77 to 0.84), and 0.80 (95% ci: 0.76 to 0.85), respectively (figure 3). results also showed that the imact extended (or=1.00; 95% ci: 0.94 to 1.07; p=0.968) and impact lab (or=1.00; 95% ci: 0.93 to 1.07; p=0.986) have no difference with crash ct model in predicting the mortality of head trauma patients. 3.4. comparing the predictive values for unfavorable outcomes crash basic and impact core model the auc for the crash basic and impact core models in predicting the 6-month unfavorable outcome of head trauma this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e27 figure 2: comparison of area under the curve (auc) of crash basic model and impact core model in prediction of mortality in traumatic brain injury. ci: confidence interval. patients were 0.82 (95% ci: 0.78 to 0.86) and 0.80 (95% ci: 0.77 to 0.83), respectively (figure 4). these two models have no difference in predicting the unfavorable outcome of patients (diagnostic or=0.98; 95% ci: 0.93 to 1.03; p=0.462). crash ct, impact extended, and impact lab model the analysis showed that the area under the curve of the crash ct, impact extended, and impact lab models in predicting the unfavorable outcome of head trauma patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 6 figure 3: comparison of area under the curve (auc) of crash ct model, impact extended model, and impact lab model in prediction of mortality in traumatic brain injury. ci: confidence interval. are 0.81 (95% ci: 0.76 to 0.86), 0.82 (95% ci: 0.78 to 0.85), and 0.80 (95% ci: 0.75 to 0.85), respectively (figure 5). it was also obtained that the imact extended (or=1.01; 95% ci: 0.95 to 1.08; p=0.729), and the impact lab model (or=0.99; 95% ci: 0.93 to 1.06; p=0.819) have no difference with crash ct in predicting the unfavorable outcome of head trauma patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e27 figure 4: comparison of area under the curve (auc) of crash basic model and impact core model in prediction of unfavorable outcome of traumatic brain injury. ci: confidence interval. 3.5. certainty of evidence assessment of certainty of evidence according to grade framework showed that the quality of evidence in the prognostic value of crash and impact models in the prediction of mortality is low, since there was severe heterogeneity (rated down one point) and a large magnitude of effect (rated up one point). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 8 figure 5: comparison of area under the curve (auc) of crash ct model, impact extended model, and impact lab model in prediction of unfavorable outcome of traumatic brain injury. ci: confidence interval. however, the level of evidence in the prognostic value of crash and impact models in the prediction of unfavorable outcome are low to very low. there was a large magnitude of effect in all subscales; therefore, the level of evidence was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e27 table 1: characteristics of eligible studies study sample size male (n) age* injury to assessment (hrs) sampling method tbi severity assessed scale outcome follow-up (day) abdollah; 2021; malaysia 281 nr nr 0 prospective all severities core / basic mortality / unfavorable 14 / 180 camarano; 2020; us, canada 26228 nr 45 (27-63) 0 retrospective moderate to severe core / basic mortality 14 castaño-leon; 2016; spain 1301 nr 40 (24-52) 48 prospective moderate to severe core / basic / extended / ct mortality / unfavorable 180 charry; 2017; colombia 127 107 >18 12 retrospective moderate to severe extended / ct / lab mortality 180 charry; 2019; colombia 309 240 >18 12 retrospective all severities extended / ct / lab mortality / unfavorable 180 dijkland; 2020; europe 1742 nr 51 (32-67) 24 prospective all severities core / basic / extended / ct /lab mortality / unfavorable 14 / 180 elahi; 2020; tanzania 2972 2452 31.1 (15.2) 0 prospective all severities core / basic unfavorable in-hospital han; 2014; singapore 300 nr 53 (20.7) 0 prospective severe core / basic / extended / ct / lab mortality / unfavorable 14 / 180 harrison; 2015; uk 2975 2263 >16 24 prospective all severities core / basic / extended / ct / lab mortality / unfavorable 180 honeybul; 2016; australia 319 260 32 (21-47) 0 prospective all severities core / basic / extended / ct /lab mortality / unfavorable 540 maeda; 2019; japan 635 442 age>16 0 retrospective severe core / basic / extended / ct unfavorable 180 majdan; 2014; austria 778 nr 50 (28-69) 48 prospective all severities core / basic / extended / ct mortality / unfavorable 180 pranav; 2022; usa, uganda 877 746 31.3 (nr) 0 prospective all severities core / basic mortality in-hospital wong; 2013; hong kong 178 127 56 (20) 0 prospective all severities core / basic mortality / unfavorable 14 / 180 wongchareon; 2020; south america 466 nr 28 (21-43) 24 retrospective severe core / basic / extended / ct / lab mortality / unfavorable 14 / 180 xu; 2022; china 341 243 54 (17.4) / 56.2(15.4) 12 amphidirectional moderate to severe core / basic mortality / unfavorable 14 / 180 *, data are presented as rang, mean (±sd) or median (iqr). basic: crash basic model; core: impact core model; ct: crash computed tomography model; extended: impact extended model; lab: impact laboratory model; nr: not reported; tbi: traumatic brain injury rated up one point. in addition, significant inconsistency was observed and the score was rated down one point in all subscales. finally, the analyses showed possible publication bias in assessing the prognostic value of impact core and impact extended models. therefore, the level of evidence for the prognostic value of impact core and impact extended models were judged as very low (table 3). 4. discussion low to very low level of evidence shows that the impact and crash models have similar values in predicting mortality and unfavorable outcome of patients with traumatic brain injury. similar findings were also observed in the sub-scores of the two models. as a result, the prognostic values of all sub-scores in predicting mortality and unfavorable outcome of traumatic brain injury secondary to trauma are similar. the results of the present study showed that impact extended and impact lab models have equal value in prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 10 table 2: risk of bias assessment of included studies study risk of bias applicability patient selection index tests reference standard flow and timing patient selection index tests reference standard abdollah; 2021 low low low low low low low camarano; 2020 low low low unclear low low low castaño-leon; 2016 low low low low low low low charry; 2017 high low low unclear low low low charry; 2019 high low low unclear low low low dijkland; 2020 low low low low low low low elahi; 2020 low low low unclear low low low han; 2014 low low low low low low low harrison; 2015 low low low low low low low honeybul; 2016 low low low low low low low maeda; 2019 low low low low low low low majdan; 2014 low low low low low low low pranav; 2022 low low low unclear low low low wong; 2013 low low low low low low low wongchareon; 2020 low low low low low low low xu; 2022 high low low unclear low low low low: low risk of bias; high: high risk of bias; unclear: unclear risk of bias. dicting mortality and unfavorable outcome of patients with traumatic brain injury. in addition to impact extended variables, the impact lab model requires serum biomarkers such as blood sugar and hemoglobin level. therefore, using the impact extended model in the clinical setting is better because it requires fewer variables for calculation. it should be noted that the crash ct model can only be calculated by adding ct scan findings to crash basic, making it easier to use clinically. the area under the curve of crash basic and impact core models are similar in predicting the outcome of patients with traumatic brain injury. to calculate the crash basic model score, variables such as the country’s economic status (developing or developed country), level of conciseness, pupils’ reaction to light, and major extracranial injury are needed. the impact core model requires variables such as age, motor score, and pupils’ reaction to light, which are not much different from the crash basic model. therefore, using either of the two models will have a similar application in managing patients with traumatic brain injury. one of the aims of the present study was to investigate the prognostic value of impact and crash models based on the severity of brain injury. the articles included in our analysis reported mild, moderate, and severe injury severity (8, 12, 44-50). however, most of the studies did not perform analysis based on the severity of injuries. to evaluate the discrimination of the two prognostic models, most of the included studies confined their results to only the area under the curve. nonetheless, it should be kept in mind that the area under the curve is the early stage in the assessment of the diagnostic accuracy and predictive value of a model. at the same time, the analysis based on a cut point that reports sensitivity and specificity is more useful in the clinical setting (51). in this regard, in addition to a systematic search, the researchers of the present study also conducted an extensive manual search to find an article that compares the prognostic value of the impact and crash models based on a cutoff point. this additional search resulted in very few studies. most studies that report sensitivity and specificity based on a cut point did not use a prespecified threshold and often tried to find the best cut point based on the youden index (52). as a result, the cut points used are very different, making it impossible to pool the data in this section. also, some studies used unconventional cutoff points, which made the sensitivity too low to report higher specificity (50, 53). however, in prognostic tools and screening tests, sensitivity is more valuable than specificity. in this regard, the results reported by wongchareon et al. (n=466) indicated that the sensitivity of crash core and crash ct models in prediction of 14-day mortality as 8% and 13%, which were associated with a specificity of 99% and 97%, respectively. they also reported the sensitivity of impact core, extended, and lab models equal to 36%, 44%, and 36%, and their specificities as 87%, 87%, and 89%, respectively (53). camarano et al. determined the optimal cutoff threshold using youden’s index; the crash basic and impact core model’s cutoff values were 33.1% and 42.8%, respectively. using these cutoff thresholds, they reported the sensitivity and specificity of the crash basic and impact core model for predicting inhospital mortality. for crash basic and impact core models, the sensitivity was 78% and 80%, and the specificity was 80% and 78%, respectively (52). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e27 table 3: certainty in evidence based on grade framework outcome/ model sample size effect size risk of bias imprecision inconsistency (i2 ) indirectness publication bias judgment and level of evidence mortality crash basic 35800 0.82 (0.77, 0.86) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect impact core 35056 0.80 (0.77, 0.84) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect crash ct 7020 0.80 (0.74, 0.86) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect impact extended 7169 0.81 (0.77, 0.84) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect impact laboratory 5502 0.80 (0.76, 0.85) not serious not serious serious not serious not present low: rated down 1 point presence of serious inconsistency rated up 1 /point large magnitude of effect unfavorable outcome crash basic 12302 0.82 (0.76, 0.86) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect impact core 11558 0.80 (0.77, 0.83) not serious not serious serious not serious likely very low: rated down 2 /points presence of serious inconsistency possible publication bias rated up 1 /point large magnitude of effect crash ct 7528 0.81 (0.76, 0.86) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect impact extended 7804 0.82 (0.78, 0.85) not serious not serious serious not serious likely very low: rated down 2 /points presence of serious inconsistency possible publication bias rated up 1 /point large magnitude of effect impact laboratory 5502 0.80 (0.75, 0.85) not serious not serious serious not serious not present low: rated down 1 /point presence of serious inconsistency rated up 1 /point large magnitude of effect grade: grading of recommendations assessment, development and evaluation; crash: corticosteroid randomization after significant head injury; impact: international mission for prognosis and analysis of clinical trials; ct: computed tomography. we also found two studies in which only one of the models was evaluated. in the first study, hashemi et al. stated that the patients whose expected risk based on the crash basic and crash ct model is equal to 63.9 and 51.2, respectively, are high-risk patients in terms of 14-day mortality. the study also introduced 43.2 and 78.7 as cutoff points for the 6-month unfavorable outcome (54). in another study using children and adolescents as the patient population, fazel et al. showed that the best cutoff points for identifying high-risk head trauma for 14-day mortality in children using crash basic and crash ct models are 46 and 30. this study reported the cutoff points for 6-month unfavorable outcome as 17 and 13 (55). another limitation was the retrospective design of some of the included studies. the retrospective method affects the risk of bias in the patient selection, flow, and timing dothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 12 main. when data is collected retrospectively, the sampling is not random, which results in a high risk of bias. similarly, flow and timing in diagnostic or prognostic studies should be such that the index test is checked first and then the reference standard (24). in retrospective studies, the outcome of the patients is known from the beginning. therefore, it is impossible to be sure of the risk of bias in the flow and timing domain. as a result, the risk of bias in these studies in the flow and timing domain was considered unclear. simplicity should be kept in mind when designing a scoring system. the fewer variables to calculate in a prognostic model, the easier its use. both the crash and impact models have a core / basic model that requires variables only from history and physical exam. they also have more complex models (ct, extended, and lab models) that include ct scans or laboratory findings in addition to the clinical findings of the patients. as figures 2 to 5 demonstrate, the area under the curve in the impact core and crash basic model is not much different from impact extended, impact lab, and crash ct models. therefore, it may be possible to check the outcome of patients only based on crash basic and impact core models. this finding has been confirmed by other studies (47, 50). after a tbi, prognostic models can help the medical team allocate resources and improve the quality of care given (13). as results showed, both models have a good discrimination power to predict tbi patients’ prognosis. their clinical use can prevent the health care system from unnecessary imaging and save time and money, and reduce the patient’s exposure to ionizing radiation. we suggest a systematic review and meta-analysis of the diagnostic value of crash and impact models in detecting intracranial hemorrhage in tbi patients. 5. conclusion our results demonstrate the similar performance and predictive value of both models in predicting mortality and unfavorable outcome of patients with traumatic brain injury. the analysis showed that the impact core model and crash basic model have equal prognostic value in predicting mortality and unfavorable outcome for patients with traumatic injuries to the brain. so, both models can aid in estimating the prognosis for tbi patients in clinical practice. the crash ct model is like the impact extended and impact lab models. since the discriminative power of the impact core and crash basic models is not different from the impact extended, impact lab, and crash ct models, it may be possible to rely only on the core and basic models in examining the prognosis of patients with traumatic brain injury. 6. declarations 6.1. acknowledgments none. 6.2. conflict of interest there is no conflict of interest. 6.3. funding information the study was funded and supported by iran university of medical sciences; grant no: 97-4-37-13848. 6.4. authors contribution study design: my, as data gathering: hz, mv, srd, har analysis: my interpretation: all authors drafting: hz, srd, har revising: all authors reading and approving final version: all authors references 1. badhiwala jh, wilson jr, fehlings mg. global burden of traumatic brain and spinal cord injury. lancet neurol. 2019;18(1):24-5. 2. 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clinical trials in traumatic brain injury models compared with a machine learning-based predictive model from tanzania. j neurotrauma. 2022;39(12):151-8. 50. warman pi, seas a, satyadev n, adil sm, kolls bj, haglund mm, et al. machine learning for predicting inhospital mortality after traumatic brain injury in both high-income and lowand middle-income countries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e27 neurosurgery. 2022;90(5):605-12. 51. halligan s, altman dg, mallett s. disadvantages of using the area under the receiver operating characteristic curve to assess imaging tests: a discussion and proposal for an alternative approach. eur radiol. 2015;25(4):932-9. 52. camarano jg, ratliff ht, korst gs, hrushka jm, jupiter dc. predicting in-hospital mortality after traumatic brain injury: external validation of crash-basic and impact-core in the national trauma data bank. injury. 2021;52(2):147-53. 53. wongchareon k, thompson hj, mitchell ph, barber j, temkin n. impact and crash prognostic models for traumatic brain injury: external validation in a southamerican cohort. inj prev. 2020;26(6):546-54. 54. hashemi b, amanat m, baratloo a, forouzanfar mm, rahmati f, motamedi m, et al. validation of crash model in prediction of 14-day mortality and 6-month unfavorable outcome of head trauma patients. emerg (tehran). 2016;4(4):196-201. 55. fazel m, ahmadi s, hajighanbari mj, baratloo a, shahsavarinia k, hosseini m, et al. validation of crash model in prediction of 14-day mortality and 6-month unfavourable outcome of pediatric traumatic brain injury. int j pediatr. 2019;7(12):10413-22. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 16 appendix 1: medline (pubmed) search query medline (via pubmed) 1. "decision support techniques" [mesh] or international mission for prognosis and analysis of clinical trials in traumatic brain injury[tiab] or impact prognostic models[tiab] or impact prognostic model[tiab] or impact rule[tiab] or impact model[tiab] or impact core[tiab] or impact basic[tiab] or impact-core[tiab] or impact-basic[tiab] or impact ct[tiab] or impact lab[tiab] or impactct[tiab] or impact-lab[tiab] or corticosteroid randomization after significant head injury[tiab] or crash prognostic models[tiab] or crash prognostic model[tiab] or crash rule[tiab] or crash model[tiab] or crash core[tiab] or crash basic[tiab] or crash ct[tiab] or crash-basic[tiab] or crash-ct[tiab] 2. "brain concussion"[mesh] or "brain injuries"[mesh] or "brain injuries, traumatic"[mesh] or brain concussion[tiab] or brain injuries[tiab] or brain injuries, traumatic[tiab] or brain concussions[tiab] or concussion, brain[tiab] or commotio cerebri[tiab] or cerebral concussion[tiab] or cerebral concussions[tiab] or concussion, cerebral[tiab] or concussion, intermediate[tiab] or intermediate concussion[tiab] or intermediate concussions[tiab] or concussion, severe[tiab] or severe concussion[tiab] or severe concussions[tiab] or concussion, mild[tiab] or mild concussion[tiab] or mild concussions[tiab] or mild traumatic brain injury[tiab] or injuries, brain[tiab] or brain injury[tiab] or injury, brain[tiab] or injuries, acute brain[tiab] or acute brain injuries[tiab] or acute brain injury[tiab] or brain injury, acute[tiab] or injury, acute brain[tiab] or brain injuries, acute[tiab] or brain lacerations[tiab] or brain laceration[tiab] or laceration, brain[tiab] or lacerations, brain[tiab] or brain injuries, focal[tiab] or brain injury, focal[tiab] or focal brain injury[tiab] or injuries, focal brain[tiab] or injury, focal brain[tiab] or focal brain injuries[tiab] or brain injury, traumatic[tiab] or traumatic brain injuries[tiab] or trauma, brain[tiab] or brain trauma[tiab] or brain traumas[tiab] or traumas, brain[tiab] or encephalopathy, traumatic[tiab] or encephalopathies, traumatic[tiab] or traumatic encephalopathies[tiab] or injury, brain, traumatic[tiab] or traumatic encephalopathy[tiab] or traumatic brain injury[tiab] or tbi[tiab] 3. #1 and #2 embase 1. ’international mission for prognosis and analysis of clinical trials in traumatic brain injury’:ab,ti or ’impact prognostic models’:ab,ti or ’impact rule’:ab,ti or ’impact model’:ab,ti or ’impact core’:ab,ti or ’impact basic’:ab,ti or ’impact-core’:ab,ti or ’impact-basic’:ab,ti or ’impact ct’:ab,ti or ’impact lab’:ab,ti or ’impact-ct’:ab,ti or ’impact-lab’:ab,ti or ’corticosteroid randomization after significant head injury’:ab,ti or ’crash prognostic models’:ab,ti or ’crash prognostic model’:ab,ti or ’crash rule’:ab,ti or ’crash model’:ab,ti or ’crash core’:ab,ti or ’crash basic’:ab,ti or ’crash ct’:ab,ti or ’crash-basic’:ab,ti or ’crash-ct’:ab,ti 2. ’brain injury’/exp or ’brain injury’ or ’head injury’/exp or ’head injury’ or ’traumatic brain injury’/exp or ’traumatic brain injury’ 3. #1 and #2 scopus 1title-abs-key("international mission for prognosis and analysis of clinical trials in traumatic brain injury" or "impact prognostic models" or "impact prognostic model" or "impact rule" or "impact model" or "impact core" or "impact basic" or "impactcore" or "impact-basic" or "impact ct" or "impact lab" or "impact-ct" or "impact-lab" or "corticosteroid randomization after significant head injury" or "crash prognostic models" or "crash prognostic model" or "crash rule" or "crash model" or "crash core" or "crash basic" or "crash ct" or "crash-basic" or "crash-ct") 2title-abs-key ("brain concussion" or 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traumatic" or "traumatic brain injuries" or "trauma, brain" or "brain trauma" or "brain traumas" or "traumas, brain" or "tbi (traumatic brain injury)" or "encephalopathy, traumatic" or "encephalopathies, traumatic" or "traumatic encephalopathies" or "injury, brain, traumatic" or "traumatic encephalopathy" or "traumatic brain injury") 3#1 and #2 web of science 1ts=("international mission for prognosis and analysis of clinical trials in traumatic brain injury" or "impact prognostic models" or "impact prognostic model" or "impact rule" or "impact model" or "impact core" or "impact basic" or "impact-core" or "impact-basic" or "impact ct" or "impact lab" or "impact-ct" or "impact-lab" or "corticosteroid randomization after significant head injury" or "crash prognostic models" or "crash prognostic model" or "crash rule" or "crash model" or "crash core" or "crash basic" or "crash ct" or "crash-basic" or "crash-ct") 2ts= ("brain concussion" or "brain injuries" or "brain injuries, traumatic" or "brain concussion" or "brain injuries" or "brain injuries, traumatic" or "brain concussions" or "concussion, brain" or "commotio cerebri" or "cerebral concussion" or "cerebral concussions" or "concussion, cerebral" or "concussion, intermediate" or "intermediate concussion" or "intermediate concussions" or "concussion, severe" or "severe concussion" or "severe concussions" or "concussion, mild" or "mild concussion" or "mild concussions" or "mild traumatic brain injury" or "injuries, brain" or "brain injury" or "injury, brain" or "injuries, acute brain" or "acute brain injuries" or "acute brain injury" or "brain injury, acute" or "injury, acute brain" or "brain injuries, acute" or "brain lacerations" or "brain laceration" or "laceration, brain" or "lacerations, brain" or "brain injuries, focal" or "brain injury, focal" or "focal brain injury" or "injuries, focal brain" or "injury, focal brain" or "focal brain injuries" or "brain injury, traumatic" or "traumatic brain injuries" or "trauma, brain" or "brain trauma" or "brain traumas" or "traumas, brain" or "encephalopathy, traumatic" or "encephalopathies, traumatic" or "traumatic encephalopathies" or "injury, brain, traumatic" or "traumatic encephalopathy" or "traumatic brain injury" or "tbi") 3#1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 17 archives of academic emergency medicine. 2023; 11(1): e27 figure s 1: publication bias of impact and crash prognostic models in mortality prediction across eligible studies. there is no evidence of publication bias across the studies. effect size is the area under the curve. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index h. zarei et al. 18 figure s 2: publication bias of impact and crash prognostic models in predicting 6-month unfavorable outcome across eligible studies. there is evidence of possible publication bias in detecting the prognostic value of impact core and impact extended models. effect size is the area under the curve. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e9 or i g i n a l re s e a rc h oral piracetam vs betahistine in outpatient management of peripheral vertigo; a randomized clinical trial ali arhami dolatabadi1, seyedeh roghieh larimi1, arash safaie2∗ 1. emergency department, imam hossein hospital, medical school, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: october 2018; accepted: december 2018; published online: 23 january 2019 abstract: introduction: although vertigo is a common complaint in patients presenting to the emergency department (ed), its ideal treatment is still under debate. this study was conducted to compare oral betahistine and oral piracetam in management of outpatients with peripheral vertigo. methods: this was a randomized clinical trial performed on patients who were presented to the eds of 4 teaching hospitals, with complaint of true vertigo. patients were randomly allocated to either betahistine or piracetam group and their 7-day outcomes were compared. results: 100 cases with the mean age of 54.72 ± 14.09 years were randomly allocated to either group (62.0% female). the two groups were similar regarding age, sex, and intensity of symptom at the time of presenting to the ed. twelve (24%) patients in piracetam group and 6 (12%) patients in betahistine group experienced adverse events (odds ratio: 2.32, ci 95%: 0.79-6.76; p = 0.125). there were 3 (6%) patients in each group that experienced a recurrence of their symptoms and 2 (4%) patients in each group saw another physician for vertigo. conclusion: oral piracetam is a potentially proper treatment for management of peripheral vertigo and there are few adverse effects associated with it. keywords: vertigo; piracetam; betahistine; emergency medicine; treatment outcome cite this article as: arhami dolatabadi a, larimi s r, safaie a. oral piracetam vs betahistine in outpatient management of peripheral vertigo; a randomized clinical trial. arch acad emerg med. 2019; 7(1): e9. 1. introduction vertigo is an illusion of movement when there is no motion (1, 2). it is a common complaint in patients presenting to the emergency department (ed) and categorized as peripheral or central vertigo (1-3). although ideally the underlying cause of vertigo should be treated, peripheral vertigo is usually treated symptomatically. different drugs from various pharmacologic categories are used to treat peripheral vertigo, including antiemetics, anticholinergics, antihistamines, and calcium channel blockers. despite the availability of various options for symptomatic treatment of vertigo, a drug of choice has not been defined yet. there are sometimes paradoxical data on the effectiveness of each drug for symptomatic treatment of vertigo (1, 4). betahistine is one of the common medications, which is currently used to treat peripheral vertigo. piracetam is a cyclic derivative of neuro∗corresponding author: arash safaie; sina hospital, imam khomeini avenue, tehran, iran. tel: +989111366966 fax: +982163121413 email: asafaie@sina.tums.ac.ir transmitter gamma-aminobutyric acid, which might be effective in treatment of vertigo (5-10). by using the combination of betahistine and piracetam in management of peripheral vestibular vertigo oleg and colleagues concluded that this combination may be more effective than piracetam alone in this regard (11). intravenous piracetam was as effective as intravenous dimenhydrinate in relieving symptom of vertigo patients in dugan et al. study (12). however, the evidence regarding effectiveness of oral piracetam after acute manifestation of peripheral vertigo is sparse. therefore, this study aimed to compare oral betahistine and oral piracetam in outpatient management of peripheral vertigo. 2. methods 2.1. study design and setting this randomized clinical trial was conducted on patients who presented to the emergency departments of imam hossein, shohadaye tajrish, loghman hakim and sina hospitals, tehran, iran, throughout 2016, complaining from true vertigo. all of these hospitals are teaching hospitals. eththis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. arhami dolatabadi et al. 2 ical approval was obtained from shahid beheshti medical university ethics committee (ir.sbmu.sm.rec.1394.25) and the study was registered on iranian registry of clinical trials with code number: irct2016011921063n3. informed consent was obtained from each patient prior to his or her enrollment in the study. 2.2. participants patients with acute vertigo who were discharged from the emergency department were included. exclusion criteria were age below 18 years, prior history of sensitivity to betahistine or piracetam, consumption of drugs which can possibly improve vertigo (antihistamines, benzodiazepines or anticholinergics), history of peptic ulcer disease or pheochromocytoma, patients who did not give consent to participate in the study, patients with central vertigo and patients who were lost to follow-up. 2.3. intervention patients were enrolled using convenience sampling method and were randomly assigned to either piracetam or betahistine group. upon discharge, piracetam group patients received 800 mg piracetam tablets (darou pakhsh pharma chem co., tehran, iran) every 8 hours for 7 days and betahistine group patients received 8 mg betahistine tablets (betaserc ®, abbott healthcare sas, chatillon-sur-chalaronne, france) every 8 hours for 7 days. simple randomization was done using a random numbers table, which was generated using stattrek website “http://stattrek.com/statistics/random-numbergenerator.aspx”. 2.4. outcomes the primary outcome was vertigo intensity control 7 days after discharge from ed. the secondary outcomes were nausea and fatigue intensities control 7 days after discharge from ed, drug compliance, and adverse events. 2.5. data gathering data were acquired using face to face interview with patients at the times of presenting to ed and discharge from ed and using telephone interview 7 days after discharge. patients’ vertigo, nausea, and fatigue intensities were investigated using 10-point numeric rating scale (nrs). we asked patients about their compliance (taking piracetam or betahistine) using 5-point likert scale and the occurrence of any complication while taking medications. patients were asked about the recurrence of their vertigo symptoms, visiting another physician for vertigo or requiring hospitalization because of vertigo during the 7-day period after discharge from ed. an emergency physician and a 3r d year emergency medicine resident were responsible for patients’ allocation and data flowchart 1: consort flow diagram of the studied patients. gathering. the prescribing physicians and the patients were not blinded. however, both the physician who interviewed the patients 7 days after their discharge and the statistical analyst were blinded to the prescribed drug. 2.6. statistical analysis we analyzed data using spss software version 21 and intention to treat analysis method. categorical data were analyzed using chi-square or fisher’s exact tests. quantitative data were analyzed using t-test, mann-whitney or kruskal-wallis tests. the sample size of 48 patients in each group was calculated. failure to control symptoms was defined as score ≥ 3 7 days after taking medicines. p < 0.05 was considered statistically significant. 3. results 3.1. baseline characteristics one hundred twenty-two patients were assessed for eligibility, out of which 18 cases were excluded for various reasons (flowchart 1). there were 4 (3.8%) cases of loss to follow up. finally, 100 cases with the mean age of 54.72 ± 14.09 (18-90) years were randomly allocated to each group (62.0% female). baseline characteristics of the studied patients are compared in table 1. the two groups were similar regarding age, sex, and intensity of symptom at the time of presenting to the emergency department and discharge. 3.2. outcome there were no statistically significant differences between two groups regarding intensity of vertigo, nausea and fatigue 7 days after discharge from ed. twelve (24%) patients in piracetam group and 6 (12%) patients in betahistine group experienced adverse events (odds ratio: 2.32, ci 95%: 0.79this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e9 table 1: baseline characteristics of the studied patients variables groups p piracetam n=50 betahistine n=50 age 56.36 ± 12.92 53.08 ± 15.13 0.245 sex male 21 (42.0) 17 (34.0) 0.268 female 29 (58.0) 33 (66.0) intensity of symptom (on presentation) vertigo 8.36 ± 1.98 8.44 ± 1.63 0.844 nausea 8.24 ± 2.50 7.52 ± 2.87 0.136 fatigue 4.98 ± 3.18 5.16 ± 2.92 0.723 intensity of symptom (on discharge) vertigo 1.82 ± 1.08 1.58 ± 0.73 0.397 nausea 1.22 ± 0.55 1.26 ± 0.44 0.455 fatigue 1.42 ± 1.07 1.22 ± 0.55 0.415 data are presented as mean ± standard deviation or frequency (%). table 2: comparing the outcomes between the two groups 7 days after discharge from emergency department outcome groups p piracetam n=50 betahistine n=50 vertigo intensity 1.78 ± 1.38 1.84 ± 1.20 0.648 success 48 (96.0) 48 (96.0) 0.691 failure* 2 (4.0) 2 (4.0) nausea intensity 1.12 ± 0.52 1.10 ± 0.21 0.987 success 49 (98.0) 50 (100.0) 0.500 failure* 1 (2.0) 0 (0) fatigue intensity 1.28 ± 0.67 1.36 ± 1.41 0.437 success 49 (98.0) 48 (96.0) 0.500 failure* 1 (2.0) 2 (4.0) secondary outcomes drug compliance 4.52 ± 0.58 4.58 ± 0.50 0.713 adverse events 12 (24.0) 6 (12.0) 0.125 *: score ≥ 3 seven days after discharge. data are presented as mean ± standard deviation or frequency (%). 6.76; p = 0.125). there were 3 (6%) patients in each group who experienced a recurrence of their symptoms and 2 (4%) patients in each group saw another physician for vertigo. the symptoms of one patient in the piracetam group were so severe that required hospitalization on the 7t h day after discharge from ed. there was not any significant difference between groups regarding failure to control symptoms. 4. discussion based on the findings, there was not any significant difference between oral betahistine and oral piracetam regarding recurrence, relieving vertigo, nausea, and fatigue symptoms 7 days after discharge from ed. adverse events in the two groups were comparable as well. despite being a common presentation in both ed and general settings, the ideal treatment for vertigo is still under debate (1, 4). betahistine dihydrochloride is a drug with structural similarity to histamine (13, 14). betahistine is a strong h3 receptor antagonist and a weak h1 receptor agonist, which is relatively inactive at h2 receptor (13-15). betahistine increases cochlear blood flow via h3 receptor antagonism (16). it also increases histamine turnover in central and vestibular nervous systems and decreases vestibular sensory input through the same mechanism. betahistine has excitatory effects on cortical and subcortical neuronal activity by h1 receptor agonist (13-15). betahistine has been used for treating vertigo for years and its effectiveness was shown in many studies (7, 13-15, 17-22). in a cochrane review conducted by murdin, 16 studies comparing betahistine and placebo in different vertigo types were included. pooled data showed that betahistine was better than placebo in reducing vertigo symptoms and the proportion of patients reporting an overall reduction of their vertigo symptoms was higher in the betahistine group (risk rathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. arhami dolatabadi et al. 4 tio (rr)= 1.30, 95% confidence interval (ci)= 1.05 to 1.60). however, statistical heterogeneity of data was high. the most common adverse effects were gastrointestinal symptoms and headache, which were statistically similar in both groups (16% in betahistine group and 15% in placebo group and rr= 1.03, 95% ci= 0.76 to 1.40). authors concluded that low quality evidence suggests that betahistine may have a positive effect on reduction of vertigo symptoms and there is a low risk of adverse events associated with betahistine (13). it has been shown that piracetam might be effective on both chronic and acute vertigo (6-10, 23). although the exact mechanism by which piracetam affects vertigo is not determined yet, it seems to be due to an increase in vestibular compensation by exerting effects on neurotransmission and microcirculation; which result from its effects on cell membrane fluidity (8, 10, 24, 25). there are previous studies, which have evaluated the effectiveness of piracetam in various vertigo settings. ozdemir and dogan compared intravenous piracetam with intravenous dimenhydrinate in the acute setting in two separate studies. both studies showed that intravenous piracetam and intravenous dimenhydrinate have similar effectiveness in improving acute vertigo (6, 9). in a study by akdogan, oral piracetam and placebo were compared in chronic vertigo lasting more than 3 months. piracetam was more effective than placebo in treating all of the symptoms (5). in a sub-analysis of data from osvald study, which was conducted by melnikov, it was shown that piracetam and betahistine combination therapy is more effective than treatment with betahistine alone in patients with peripheral vestibular vertigo(7). rosenhal evaluated the effectiveness of betahistine in comparison with placebo for treating chronic vertigo in a multicenter, randomized clinical trial. piracetam was more effective than placebo in decreasing frequency of vertigo episodes, interval malaise, and imbalance (10). in a study by ince gunal, patients with autosomal dominant cerebellar ataxia were given intravenous piracetam. it was shown that piracetam causes improvement in posture and gait disturbances of these patients (23). it seems that oral piracetam is an alternative choice for treatment of peripheral vertigo and should be considered for inand out-patient management of peripheral vertigo. 5. limitation the patients and allocating physician were not blinded to the prescribed drugs. there was no placebo group in the study. we cannot rule out the probability of spontaneous recovery of vertigo, nausea and fatigue symptoms of the patients in the seven-day period after the initial presentation to ed. because of the small sample size and differences in the settings of previous studies, it is hard to reach a definite conclusion about the role of piracetam in vertigo treatment. it seems that there is a need for larger, multicenter studies and meta-analyses for a strong conclusion. 6. conclusion based on the findings, there was not any significant difference between oral betahistine and oral piracetam regarding recurrence, relieving vertigo, nausea, and fatigue symptoms, as well as adverse events 7 days after discharge from ed. 7. appendix 7.1. acknowledgements the authors wish to thank all emergency department staff of imam hossein, shohadaye tajrish, loghman hakim and sina hospitals for their contribution. this article is extracted from the residency thesis of seyedeh roghieh larimi. 7.2. author contribution ali arhami dolatabadi: idea development, and supervising the team. seyedeh roghieh larimi: patient allocation, initial interview, and writing the manuscript. arash safaie: follow up interview with the patients, statistical analysis, and writing the manuscript. authors’ orcids ali arhami dolatabadi: 0000-0001-9492-9520 arash safaie: 0000-0002-1127-6681 7.3. funding/support none. 7.4. conflict of interest none. references 1. omron r. peripheral vertigo. emerg med clin north am. 2019;37(1):11-28. 2. spiegel r, kirsch m, rosin c, rust h, baumann t, sutter r, et al. dizziness in the emergency department: an update on diagnosis. swiss med wkly. 2017;147:w14565. 3. shahrami a, norouzi m, kariman h, hatamabadi hr, arhami dolatabadi a. true vertigo patients in emergency department; an epidemiologic study. 2016. 2016;4(1):4. 4. spiegel r, rust h, baumann t, friedrich h, sutter r, goldlin m, et al. treatment of dizziness: an interdisciplinary update. swiss med wkly. 2017;147:w14566. 5. akdogan o, hn. a, s. b. kronik vertigolu hastalarda oral pirasetam kullanimi. turk arch otolaryngol. 2003(41):139-45. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e9 6. dogan no, avcu n, yaka e, yilmaz s, pekdemir m. comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial. emerg med j. 2015;32(7):520-4. 7. melnikov oa, lilenko sv, nauta j, ouwens mj. betahistine plus piracetam dual therapy versus betahistine monotherapy for peripheral vestibular vertigo: a confounder-corrected subanalysis of the osvald study. curr med res opin. 2015;31(11):1951-62. 8. oosterveld wj. the effectiveness of piracetam in vertigo. pharmacopsychiatry. 1999;32 suppl 1:54-60. 9. ozdemir h, akinci e, coskun f. comparison of the effectiveness of intravenous piracetam and intravenous dimenhydrinate in the treatment of acute peripheral vertigo in the emergency department. singapore med j. 2013;54(11):649-52. 10. rosenhall u, deberdt w, friberg u, kerr a, oosterveld w. piracetam in patients with chronic vertigo. clinical drug investigation. 1996;11(5):251-60. 11. melnikov oa, lilenko sv, nauta j, ouwens mj. betahistine plus piracetam dual therapy versus betahistine monotherapy for peripheral vestibular vertigo: a confounder-corrected subanalysis of the osvald study. current medical research and opinion. 2015;31(11):195162. 12. dogan no, avcu n, yaka e, yilmaz s, pekdemir m. comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial. emerg med j. 2015;32(7):520-4. 13. murdin l, hussain k, schilder ag. betahistine for symptoms of vertigo. cochrane database syst rev. 2016(6):cd010696. 14. ramos alcocer r, ledezma rodriguez jg, navas romero a, cardenas nunez jl, rodriguez montoya v, deschamps jj, et al. use of betahistine in the treatment of peripheral vertigo. acta otolaryngol. 2015;135(12):1205-11. 15. strupp m, zwergal a, feil k, bremova t, brandt t. pharmacotherapy of vestibular and cerebellar disorders and downbeat nystagmus: translational and backtranslational research. ann n y acad sci. 2015;1343:2736. 16. dziadziola jk, laurikainen el, rachel jd, quirk ws. betahistine increases vestibular blood flow. otolaryngol head neck surg. 1999;120(3):400-5. 17. lacour m. betahistine treatment in managing vertigo and improving vestibular compensation: clarification. j vestib res. 2013;23(3):139-51. 18. albu s, chirtes f, trombitas v, nagy a, marceanu l, babighian g, et al. intratympanic dexamethasone versus high dosage of betahistine in the treatment of intractable unilateral meniere disease. am j otolaryngol. 2015;36(2):205-9. 19. chavez h, vega r, soto e. histamine (h3) receptors modulate the excitatory amino acid receptor response of the vestibular afferents. brain res. 2005;1064(1-2):1-9. 20. djelilovic-vranic j, alajbegovic a, tiric-campara m, volic a, sarajlic z, osmanagic e, et al. betahistine or cinnarizine for treatment of meniere’s disease. med arch. 2012;66(6):396-8. 21. jeck-thole s, wagner w. betahistine: a retrospective synopsis of safety data. drug saf. 2006;29(11):1049-59. 22. lacour m, van de heyning ph, novotny m, tighilet b. betahistine in the treatment of meniere’s disease. neuropsychiatr dis treat. 2007;3(4):429-40. 23. ince gunal d, agan k, afsar n, borucu d, us o. the effect of piracetam on ataxia: clinical observations in a group of autosomal dominant cerebellar ataxia patients. j clin pharm ther. 2008;33(2):175-8. 24. winblad b. piracetam: a review of pharmacological properties and clinical uses. cns drug rev. 2005;11(2):169-82. 25. winnicka k, tomasiak m, bielawska a. piracetam–an old drug with novel properties? acta pol pharm. 2005;62(5):405-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2022; 10(1): e78 rev i ew art i c l e from q/non-q myocardial infarction to stemi/nstemi: why it’s time to consider another simplified dichotomy; a narrative literature review grigorios avdikos1∗, george michas2, stephen w. smith3 1. department of cardiology, bioiatriki healthcare group, 132 kifisias ave. & papada st., 11526, athens, greece. 2. department of cardiology, “elpis” general hospital of athens, dimitsanas 7, 11522, athens, greece. 3. hennepin healthcare, university of minnesota school of medicine, hcmc er, r-2, 701 s. park ave., minneapolis, mn 55415, united states of america. received: july 2022; accepted: august 2022; published online: 1 october 2022 abstract: acute coronary syndromes (acss) are classified as st-segment elevation myocardial infarction (stemi) and non-st-segment elevation myocardial infarction (nstemi) based on the presence of guideline-recommended st-segment elevation (ste) criteria on the electrocardiogram (ecg). stemi is associated with acute total coronary occlusion (ato) and transmural myocardial necrosis and is managed with emergent reperfusion therapy, and nstemi is supposedly synonymous with subendocardial myocardial infarction without ato. however, coronary angiograms reveal that a significant proportion of patients with nstemi have ato. here, we review articles that studied the frequency and cardiovascular outcomes of ato in nstemi patients compared with those without ato. we discuss ecg patterns of patients with suspected acute myocardial infarction that do not fulfill stemi criteria but are associated with ato. under-recognition of these atypical patterns results in delays to reperfusion therapy. we also advocate revision of the current stemi/nstemi paradigm because consideration of ste, by itself, out of context of other clinical and ecg features, leads to the ecg diagnosis of stemi when the ecg actually represents a mimic [“pseudo-stemi”], and suggest renaming the acss classification as the occlusion myocardial infarction (omi)/non-occlusion myocardial infarction (nomi) paradigm. keywords: acute coronary syndrome; coronary occlusion; myocardial infarction; myocardial reperfusion; non-st elevated myocardial infarction cite this article as: avdikos g, michas g, smith sw. from q/non-q myocardial infarction to stemi/nstemi: why it’s time to consider another simplified dichotomy; a narrative literature review. arch acad emerg med. 2022; 10(1): e78. https://doi.org/10.22037/aaem.v10i1.1783. 1. introduction acute coronary syndromes (acss) remain a leading cause of morbidity and mortality worldwide. the 12-lead electrocardiogram (ecg) is a valuable tool for early recognition of acute myocardial ischemia. the presence or absence of pathologic q waves on the ecg formerly resulted in classification of acute myocardial infarction (ami) as q-wave or non-q-wave myocardial infarction (mi). in 2000, the acc/aha guidelines (1) announced a paradigm shift: patients presenting with st-segment elevation (ste) on the ecg were grouped as having st-segment elevation acute myocardial infarction ∗corresponding author: grigorios avdikos; department of cardiology, bioiatriki healthcare group, 132 kifisias ave. & papada st., 11526, athens, greece. email: goranavdi@yahoo.gr, tel: +306942906463, orcid: https://orcid.org/0000-0002-1890-1646. (stemi) and those without ste as non-st-segment elevation myocardial infarction (nstemi). stemi would purportedly represent acute total coronary occlusion (ato) myocardial infarction (occlusion mi or omi) and nstemi would purportedly represent ami without ato (non-occlusion mi or nomi). prompt recognition of ste in the pre-hospital setting or in the emergency department by the paramedics and/or physicians is of great importance because the treatment of stemi is urgent reperfusion with thrombolytics or primary coronary intervention. however, in reality, many patients who present with nstemi have ato or subtotal occlusion on the coronary angiogram. a meta-analysis of seven studies showed that 25.5% of nstemi patients had ato with increased adverse short and medium to long term cardiovascular outcomes, compared with nstemi patients without ato (2). furthermore, advances in ecg interpretation have revealed numerous high-risk ecg presentations without ste this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 2 that are associated with ato for which early reperfusion therapy could be beneficial. the aim of the current narrative review is to study the frequency and cardiovascular outcomes of ato in nstemi patients, provide a summary of ecg patterns without ste that are associated with ato, and support a paradigm shift of the current stemi/nstemi classification of acs. 2. methods we searched the electronic database of pubmed from inception up to 22 august 2022 for articles that studied: i) patients who underwent percutaneous coronary angiogram/intervention (pci) for nstemi, ii) the incidence (or prevalence) of ato on the coronary angiogram of this population, and iii) cardiovascular outcomes of patients with ato compared with those without ato. exclusion criteria included non-english manuscripts, case reports and editorials. the following terms were used: (incidence or prevalence or frequency) and (impact or outcomes) and (total artery occlusion or culprit lesion) and (nstemi or non-st elevation myocardial infarction). the titles and abstracts were reviewed, independently, by 2 authors (ga, gm) and unrelated studies were excluded. full-text evaluation of the remaining articles was performed and studies that satisfied eligibility criteria were included in the review. disagreements between reviewers were resolved after discussion with the third author (ss). similar articles of the selected studies were also evaluated for eligibility. figure 1 shows the flow diagram of the study. 3. findings 3.1. outcomes of nstemi cases with ato we identified 192 records. four observational studies and 2 meta-analyses were included in the present review. in a systematic review and meta-analysis (3) data from 25 studies were analyzed, the average proportion of ato in nstemi patients was 34% (95% ci 30%-37%). death rate, recurrent mi and cardiogenic shock were significantly higher in ato nstemi patients compared with those without ato (or: 1.72, 95% ci: 1.49-1.98, p < 0.001, or 1.7: 95% ci: 1.06-2.75, p = 0.029 and or: 1.66, 95% ci: 1.35-2.04, p < 0.001, respectively). khan et al. (2) published a systematic review and meta-analysis of 7 studies and reported thrombolysis in myocardial infarction (timi) flow 0-1 in 25.5% of nstemi patients. this group had increased short and medium-to longterm risk of major adverse cardiovascular events (mace) (rr: 1.41, 95% ci: 1.17-1.70, p = 0.0003 and rr: 1.32, 95% ci: 1.111.56, p = 0.001, respectively) and all-cause mortality (rr: 1.67, 95% ci: 1.31-2.13, p<0.0001 and rr: 1.42, 95% ci: 1.08-1.86, p=0.01, respectively). more recently, in a large polish registry (4) the proportion of ato with timi flow 0 was 19.9% among 81415 nstemi patients and was associated with higher incidence of cardiac arrest before admission (3.09% vs. 2.19%, p<0.0001), killip class iv on admission (2.48% vs. 1.69%, p<0.0001), death during pci (0.97% vs. 0.43%, p<0.0001), and the lower frequency of timi flow 3 after pci (83.36% vs. 88.61%, p<0.0001). morawska et al. (5) found increased in-hospital and oneyear mortality in nstemi patients presenting with ato compared with nstemi patients with patent coronary arteries (2.8 % vs. 1.1%, p=0.007 and 18.1% vs. 6.5%, p<0.001, respectively). another observational study (6) found statistically insignificant differences between ato and non-ato nstemi patients regarding inhospital (5.3% vs. 1%, p=0.07) and 6month mace (5.4% vs. 4.6%, p=0.24). fernando et al. (7) studied the long-term cardiovascular outcomes of occluded culprit arteries in nstemi patients and found lower rates of mortality in ato nstemi patients when compared with nstemi patients without ato with an average follow up of 4.9 years (12% vs. 18%, p<0.01), despite the increased 30-day mace observed in this group (6.7% vs. 3.8%, p<0.001). multivariate analysis of this study showed that age, traditional cardiovascular risk factors, heart failure, renal impairment, and multivessel coronary artery disease are all independent predictors of long-term mortality, whereas ato was not. thus, higher rates of long-term mortality in nstemi patients without ato may be attributed to the greater prevalence of comorbidities in this group. table 1 shows published articles that studied the frequency of ato and cardiovascular outcomes in nstemi patients compared with nstemi patients without ato. overall, approximately 25%-30% of patients presenting with nstemi have ato with increased adverse short-term cardiovascular outcomes compared with nstemi patients with patent coronary arteries, with some discrepancies regarding long-term cardiovascular outcomes. 3.2. high-risk ecg patterns associated with ato according to the fourth universal definition of mi, ecg criteria for stemi diagnosis are ste ≥1 mm in two contiguous leads, except leads v2-v3 where the following cut-points apply: ≥2 mm in men ≥40 years; ≥2.5 mm in men <40 years or ≥1.5 mm in women regardless of age (8). these current formal criteria are based on the modification of the 2000 acc/esc criteria by macfarlane et al. (9) however, some patients present with ecg patterns that are associated with ato but do not fulfill the above-mentioned stemi criteria. below, we briefly discuss these ecg patterns. acute myocardial infarction is a dynamic phenomenon and hyperacute t waves often precede ste. there is not a clear definition of hyperacute t waves, but they are often described as symmetric, tall, with high amplitude proportional this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e78 to the qrs and depend mainly on recognition rather than on criteria (10). an old study (11) found that a combination of j point/t wave amplitude >25%, t wave/qrs amplitude >75% and j point >0.30 mv in patients >45 years old predicts clinically verifiable mi with 98% specificity and 61.9% sensitivity. many authors agree that t-wave height is not as important as t-wave “bulk,” defined as a proportion of the area under the curve of the t-wave to qrs size (10, 12, 13). diagnosis of acs in the presence of left bundle branch block (lbbb) can be challenging. sgarbossa et al. (14) proposed a score composed of 3 criteria for the diagnosis of acute mi in patients presenting with lbbb; however, it has low sensitivity. more recently, smith’s modified sgarbossa criteria were published: ste ≥1mm concordant with qrs in any lead, or stsegment depression (std) ≥ 1mm in any of leads v1-v3, or excessively discordant ste with st/s ratio ≥ 25% in any lead predicted occlusion mi (omi) in patients with lbbb (15). these criteria were validated in a study by meyers et al. (16) and showed significantly higher sensitivity and similarly high specificity compared with the original sgarbossa criteria. using a st/s ratio criterion of 20% improves sensitivity to 84% and only reduces specificity to 94%. right ventricular paced rhythm poses another diagnostic challenge. dodd et al. (17) compared smith’s modified sgarbossa criteria, which defines excessively discordant ste as an st/s ratio of 25% (with extension of the second criterion of std ≥1mm to leads v4-v6), with the original sgarbossa criteria, which defines excessively discordant ste as 5 mm, and found that it has higher sensitivity with similarly high specificity in diagnosis of omi. interpretation of the ecg in the setting of acute chest pain and new-onset right bundle branch block (rbbb) should be done with much care, because rbbb can mask subtle ste in leads v1-v3 due to secondary repolarization changes resulting in the depression of st-segment and t wave inversion. new rbbb, especially when combined with left anterior fascicular block, is associated with occlusion of proximal left anterior descending artery (lad) and increased in-hospital mortality (18). wellens’ syndrome (19, 20) is defined by a post-anginal period and ecg findings of preserved r-waves and an isoelectric or <1 mm j point elevation and biphasic t waves in leads v2-v3 (pattern a) or deeply inverted and symmetric t waves in leads v2-v3 (pattern b); the t wave changes in both types may extend to v1, v4, v5 and v6. wellens’ syndrome is related with critical stenosis of proximal lad and impending mi, and is actually a post-reperfusion pattern: if an ecg had been recorded during pain, the ecg would have manifested acute occlusion. other myocardial locations (inferior, lateral) manifest identical findings in the post-reperfusion state; in the posterior wall, it manifests as increased t-wave amplitude in v2 (“posterior reperfusion t-waves; wellens’ syndrome of the posterior wall”) (21) . more recently, de winter’s ecg pattern (22) was associated with proximal lad occlusion: minimal ste in lead avr and hyperacute t waves with upsloping std in leads v1-v6. left circumflex artery (lcx) is the culprit artery of isolated posterior mi. horizontal std of any amount, maximal in leads v1-v4 versus v5v6, predicts acute posterior omi (versus nonocclusive ischemia) with 97% specificity (23) . another ecg pattern seen in lcx total occlusion is the n wave sign, which is recognized as notch or deflection ≥2mm in the terminal qrs complex in leads ii, iii and avf and/or leads i, avl with continuous change of the notch ≥2mm in ≥2 leads in 24 hours and prolonged qrs duration in these leads (24) . aslanger’s pattern (25) is a high-risk ecg presentation connected with occlusion of lcx or right coronary artery (rca) with at least one accompanying stable but critical stenosis in one of the noninfarct-related arteries. diagnostic criteria are any ste in lead iii, with reciprocal std in avl, but no ste in other inferior leads, std in any of leads v4-v6 (but not in v2) with positive t wave and st in v1 higher than in v2. critical stenosis of the left main coronary artery (lm) or severe 3-vessel disease can present with diffuse std >1mm in at least 6 leads plus ste in avr and/or v1 (26) . marti et al. (27) found that 18% of patients with ato had subtle ste, defined as ste 0.11mm; 86% of them had timi flow grade 0/1. patients with subtle ste had longer delays to reperfusion and similar rates of deaths and reinfarction compared with those who fulfilled formal stemi criteria. reciprocal std ≥0.5 mm was present in 68% of patients with subtle stemi and more specific in 75% of patients with inferior infarctions. table 2 summarizes the high-risk ecg patterns associated with ato. 3.3. differentiation of normal, baseline ste from ste due to omi very often physicians face difficulties in diagnosing stemi because many patients have non-ischemic ste. normal variant ste (nv-ste) is sometimes referred to as “early repolarization,” even though this term has a more specific meaning. nv-ste may be present in anterior, lateral, or inferior leads. it is crucial to differentiate anterior stemi from nv-ste ecg pattern in anterior leads in the setting of acute chest pain. smith et al. (28) found a formula of 3 variables (ste 60ms after j point in lead v3, qtc segment duration, and amplitude of r wave in lead v4) that predicted anterior stemi with 86% sensitivity, 91% specificity and accuracy of 88%. after adding qrs voltage in lead v2, the accuracy of the 4-variable formula increased to 92% (29). these 2 formulas were externally validated and showed high sensitivity, specificity and diagnostic accuracy (30). moreover, presence of terminal qrs distortion (tqrsd = absence of both an s and j wave in either v2 or v3) is a useful ecg sign to differentiate anterior stemi from nv-ste with 100% specificity (i.e., no case of nv-ste had tqrsd) (31). ecg presentation of left ventricthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 4 ular aneurysm can mask acute critical occlusion of lad. criterion that supports the diagnosis of anterior stemi is any v1-v4 t wave/qrs amplitude ≥0.36 (32, 33). table 3 shows ecg patterns with normal, baseline ste and proposed criteria to differentiate ste due to omi. 3.4. from q/non-q mi to stemi/nstemi the previous paradigm of acs (q/non-q mi) reflects the natural history of mi: treatment with antithrombotics without reperfusion cannot reverse ongoing myocardial necrosis in the case of ato and it ultimately leads to large territory complete infarction, with subsequent scarring. this phenomenon is expressed with q wave on the ecg. the fibrinolytic therapy trialists’ (ftt) collaborative group, published in 1994 a landmark systematic review of 9 randomized trials, which studied the effect of fibrinolytic therapy in suspected acute mi (34). they concluded that thrombolysis was associated with reduction in mortality and this benefit was observed mainly among patients presenting with ste or bundle branch block (bbb) and when therapy was received up to 12 hours from symptom onset. however, enrollment criteria were “suspected mi”; 4/9 studies required ste but poorly defined; 5/9 had no required ecg findings; 38% of patients were enrolled after at least 6 hours of chest pain, when treatment is much less effective, and 7/9 studies used the less effective streptokinase (35-43). for example, in the second international study of infarct survival (isis-2) (37) and the anglo-scandinavian study of early thrombolysis (asset) (43) trials patients with clinically suspected acute mi and without specific ecg changes (including unspecified ste, bbb, std or normal ecg) were included and in other studies (35, 39) patients with ste ≥1mm in limb leads or ≥2mm in chest leads were deemed eligible, these cut-offs differ from those recommended in the fourth universal definition of mi for stemi diagnosis. ste and std were also retrospectively classified. based on this data, they concluded that ste is the best way to decide on thrombolytic therapy (no placebo-controlled trial of mechanical intervention has ever been done). but this is only true if ecg interpretation is crude, patients are treated after 6 hours, and streptokinase is used (not pci). but what about less obvious ste, hyperacute t-waves, st-t morphology, terminal qrs distortion, proportionality between qrs and st-t, associated q-waves, etc.? since no coronary angiograms were performed, an unknown number of patients with ecg presentations like normal ecg, pre-existing bbb, acute pericarditis, acute myocarditis, hyperkalemia, “early repolarization”, and left ventricular hypertrophy received fibrinolytic therapy without actually having acute mi. furthermore, according to the authors, it was unclear whether fibrinolytic therapy benefits patients presenting with std or other ecg abnormalities but without ste or bbb and they mentioned that the number of deaths among such patients was relatively small. due to the results of the ftt collaborative group systematic review, classification of acs changed officially from q/non-q mi to stemi/nstemi in the 2000 acc/aha guidelines. 3.5. stemi/nstemi paradigm in the era of mechanical reperfusion according to the european guidelines (44), therapy of stemi is immediate reperfusion with thrombolysis or pci, and analogous treatment (invasive therapy <2h from hospital admission) should be administered to nstemi patients with mechanical complications, cardiogenic shock, refractory angina, life-threatening arrhythmias, and acute heart failure (26). in spite of these nstemi guidelines, very few (6.4%) such patients are actually taken for angiography within 2 hours (45). early recognition of ste in the setting of acute chest pain is a critical initial step in the management of acs. however, not all ste are due to acute mi: acute pericarditis, “early repolarization”, left ventricular hypertrophy and aneurysm, takotsubo cardiomyopathy, and hyperkalemia are some examples that present with ste on the ecg. it was found that 15%-36% (46, 47) of catheter laboratory activations due to perceived stemi were false positive without culprit lesion on the coronary angiogram. major dilemmas emerge in non-pci-capable centers and time to pci >120 min, where thrombolysis is the only option for urgent reperfusion of stemi and false diagnosis could be catastrophic due to possible serious hemorrhagic complications. on the other hand, as we discussed earlier in the present review, not all acute mi with proven ato present with ste and a number of such high-risk ecg patterns can be recognized (the so-called stemi equivalents). in addition, about 25%30% of nstemi patients have ato with increased adverse cardiovascular outcomes compared with those with patent coronary arteries. strict application of stemi criteria in clinical practice excludes patients with de winter’s pattern from receiving immediate reperfusion therapy and activates catheter laboratory for patients presenting with “early repolarization” (figure 2). a “holistic” ecg approach is needed: ecg interpretation in the clinical context of acute chest pain indicative of myocardial ischemia should not focus only on st segment nor on whether any specific millimeter-based ste criteria are satisfied. in addition, st and t wave should always be assessed in proportion to qrs. 3.6. what’s new in the european guidelines? in 2017, the esc guidelines for stemi (44) in addition to the new lbbb and the isolated posterior infarction, considered two more atypical ecg presentations as high risk, which should prompt a primary coronary intervention strategy in patients presenting with ongoing symptoms consistent with myocardial ischemia: rbbb and diffuse std ≥1 mm in at this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e78 least 8 leads coupled with ste in avr and/or v1. the former pattern suggests proximal critical lad occlusion with poor prognosis and the latter points to ischemia due to left main coronary artery critical stenosis or severe multivessel disease. according to the latest esc guidelines for nstemi in 2020 (26), those presenting with std>1 mm in at least 6 leads plus ste in avr and/or v1 are also considered very high-risk patients who should be managed with immediate (<2 hours) invasive strategy. furthermore, in the supplementary data, de winter’s and wellens’ patterns are mentioned as high-risk ecg presentations without ste associated with proximal lad occlusion. there are many other subtle patterns of occlusion, which are more difficult to describe and teach. in their study (48), showing that expert ecg interpretation has equal specificity to the stemi criteria and is more than twice sensitive in detection of omi, meyers et al. found the 7 patterns shown in table 4. 3.7. the omi/nomi paradigm many authors express concerns about the clinical performance of stemi/nstemi classification of acs (49-52). misinterpretation of stemi mimics as stemi, false positive catheter laboratory activations, under-recognition of highrisk ecg patterns without ste, proper risk stratification of nstemi patients, delays to reperfusion therapy, and disagreements between emergency physicians and interventional cardiologists are common problems. the main goal in the management of patients presenting with suspected acute mi is to provide immediate reperfusion therapy to those with ato. thus, the question that should be answered is whether the patient presenting to the emergency department with chest pain has an ecg indicative of ato and not if prespecified ste criteria are fulfilled. based on this principle, meyers, weingart and smith proposed the omi/nomi research classification of acs (53). occlusion myocardial infarction (omi) is defined as an acute culprit coronary artery and either 1) timi flow 0-2 or 2) timi flow 3 plus 4th generation troponin t ≥ 1.0 ng/ml or i ≥10.0 ng/ml (5th generation, high sensitivity troponin, would be in ng/l and multiply by 1000) (48). omi refers to type 1 acute coronary syndrome involving acute occlusion or near occlusion of a major epicardial coronary vessel with insufficient collateral circulation, resulting in imminent necrosis of downstream myocardium without emergent reperfusion. omi is the anatomic and pathophysiologic substrate of stemi, but not all omi manifest as stemi. non-occlusion myocardial infarction (nomi) refers to acute mi without angiographic, laboratory or clinical evidence of omi (nstemi without ato). the term omi includes stemi patients who fulfill the current stemi criteria [stemi (+) omi] and those who do not meet these criteria [stemi (-) omi or nstemi with ato]. omi requires emergent reperfusion therapy because of ato. the diagnostic accuracy of electrocardiogram for acute coronary occlusion resulting in myocardial infarction (difoccult) study (54) found that the omi/nomi approach to ecg interpretation had superior diagnostic accuracy compared with the stemi/nstemi approach in prediction of ato and long-term mortality. meyers et al. (48) showed that stemi (-) omi (nstemi with ato) patients had significant delays to catheterization but adverse outcomes more similar to stemi (+) omi. more importantly, they found that expert ecg interpretation had sensitivity of 86% for diagnosis of omi (vs. 41% for stemi criteria) with specificity equal to stemi criteria. before the era of reperfusion therapy, anti-thrombotics (mainly aspirin and heparin) were used for the treatment of acs. in the case of a total occluded coronary artery, transmural myocardial necrosis could not be reversed and q wave was recorded on the ecg. this q/non-q paradigm was replaced by the stemi/nstemi dichotomy based on the reduced mortality of patients who presented with suspected acute mi and ste who received thrombolytic therapy. since then, ste is considered as a surrogate of ato. however, coronary angiograms revealed that not all ecg presentations with ste are due to ato and that a number of ecg patterns without ste are associated with ato. this relation is expressed by the omi/nomi paradigm. figure 3 shows a proposed evolution of acs classification. one final thought: what other pathology has been named for a test? stemi is named for one very imperfect aspect of one test (ste on the ecg). the pathology should be named for what it is: occlusion mi. its diagnosis can usually be made by expert ecg interpretation, but it is important to know that many omis do not manifest on the ecg, that many which do manifest on the ecg are not accurately interpreted by providers, and that one must often use modalities other than the ecg to make the diagnosis, including emergent echocardiogram, ct coronary angiography, or angiogram itself. for acute symptoms, initial (and especially 1or 2-hour) troponin concentration is more likely to be less than the 99th percentile and the delay to reperfusion is too long (55). 4. conclusion recent studies suggest that 25%-30% of nstemi patients have ato with increased adverse cardiovascular outcomes compared with those with patent coronary arteries. early recognition of this high-risk group of acs patients is based on the identification of ecg patterns that are related to ato and do not satisfy current stemi criteria. knowledge and continuous training in interpretation of these ecg presentations could improve management and outcomes of acs patients. considering ste as a hallmark of acute mi with ato can be at times misleading and stemi/nstemi classification should this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 6 be revised to include more high-risk ecg patterns that signify ato. we agree with renaming the paradigm as the occlusion mi/non-occlusion mi paradigm. 5. declarations 5.1. acknowledgments none. 5.2. authors’ contributions g.a. and g.m. wrote the manuscript, and searched and analyzed the data. s.s. wrote and revised the article. all authors read and approved the final version of manuscript. 5.3. funding none. 5.4. conflict of interest the authors declare that they have no competing interests. references 1. braunwald e, antman em, beasley jw, califf rm, cheitlin md, hochman js, et al. acc/aha guidelines for the management of patients with unstable angina and non-stsegment elevation myocardial infarction: executive summary and recommendations. a report of the american college of cardiology/american heart association task force on practice guidelines (committee on the management of patients with unstable angina). circulation. 2000;102(10):1193-209. doi: 10.1161/01.cir.102.10.1193. pubmed pmid: 10973852. 2. khan ar, golwala h, tripathi a, bin abdulhak aa, bavishi c, riaz h, et al. impact of total occlusion of culprit artery in acute non-st elevation myocardial infarction: a systematic review and meta-analysis. eur heart j. 2017;38(41):3082-9. 3. hung c-s, chen y-h, huang c-c, lin m-s, yeh c-f, li hy, et al. prevalence and outcome of patients with non-st segment elevation myocardial infarction with occluded “culprit” artery–a systemic review and meta-analysis. crit care 2018;22(1):1-11. 4. terlecki m, wojciechowska w, dudek d, siudak z, plens k, guzik tj, et al. impact of acute total occlusion of the culprit artery on outcome in nstemi based on the results of a large national registry. bmc cardiovasc. disord. 2021;21(1):1-9. 5. morawska i, niemiec r, stec m, wrona k, bańka p, swinarew a, et al. total occlusion of the infarctrelated artery in non-st-elevation myocardial infarction (nstemi)—how can we identify these patients? 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2020 esc guidelines for the management of acute coronary syndromes in patients presenting without persistent stsegment elevation. eur heart j. 2021;42(14):1289-367. 27. martí d, mestre jl, salido l, esteban mj, casas e, pey j, et al. incidence, angiographic features and outcomes of patients presenting with subtle st-elevation myocardial infarction. am heart j. 2014;168(6):884-90. 28. smith sw, khalil a, henry td, rosas m, chang rj, heller k, et al. electrocardiographic differentiation of early repolarization from subtle anterior st-segment elevation myocardial infarction. ann emerg med. 2012;60(1):4556. e2. 29. driver be, khalil a, henry t, kazmi f, adil a, smith sw. a new 4-variable formula to differentiate normal variant st segment elevation in v2-v4 (early repolarization) from subtle left anterior descending coronary occlusionadding qrs amplitude of v2 improves the model. j electrocardiol. 2017;50(5):561-9. 30. bozbeyoğlu e, aslanger e, yıldırımtürk ö, şimşek b, karabay cy, şimşek ma, et al. a tale of two formulas: differentiation of subtle anterior mi from benign st segment elevation. ann noninvasive electrocardiol. 2018;23(6):e12568. 31. lee dh, walsh b, smith sw. terminal qrs distortion is present in anterior myocardial infarction but absent in early repolarization. am j emerg med. 2016;34(11):21825. 32. klein lr, shroff gr, beeman w, smith sw. electrocardiographic criteria to differentiate acute anterior stelevation myocardial infarction from left ventricular aneurysm. am j emerg med. 2015;33(6):786-90. 33. smith sw. t/qrs ratio best distinguishes ventricular aneurysm from anterior myocardial infarction. am j emerg med. 2005;23(3):279-87. 34. trialists ft. indications for fibronolytic therapy in suspected acute myocardial infarction: collaborative trials of more than 1000 patients. lancet. 1994;343(8893):31122. 35. isam study group. a prospective trial of intravenous streptokinase in acute myocardial infarction (isam). n engl j med. 1986;314(23):1465-71. 36. aims trial study group. effect of intravenous apsac on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. lancet. 1988;331(8585):545-9. 37. isis-2 (second international study of infarct survival) collaborative group. randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: isis-2. j am coll cardiol. 1988;12(6sa):a3-a13. 38. late study group. late assessment of thrombolytic efficacy (late) study with alteplase 6-24 hours after onset of acute myocardial infarction. lancet. 1993;342(8874):759-66. 39. della di, miocardico sn. effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. lancet. 1986;1(8478):397-402. 40. hunt d, varigos j, dienstl f, lechleitner p, de backer g, kornitzer m, et al. isis-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs antistreplase and of aspirin plus heparin vs aspirin along among 41 299 cases of suspected acute myocardial infarction. lancet. 1992;339(8796):753-70. 41. paolasso e, ravizzini g. randomized trial of late thrombolysis in patients with suspected acute myocardial infarction. lancet. 1993;342(8874):767-72. 42. rossi p, bolognese l. comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. am j cardiol. 1991;68(6):585-92. 43. wilcox r, olsson c, skene a, von der lippe g, jensen g, hampton j, et al. trial of tissue plasminogen activator for mortality reduction in acute myocardial infarcthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 8 tion: anglo-scandinavian study of early thrombolysis (asset). lancet. 1988;332(8610):525-30. 44. ibanez b, james s, agewall s, antunes mj, bucciarelliducci c, bueno h, et al. 2017 esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc). eur heart j. 2018;39(2):119-77. 45. lupu l, taha l, banai a, shmueli h, borohovitz a, matetzky s, et al. immediate and early percutaneous coronary intervention in very high-risk and high-risk non-st segment elevation myocardial infarction patients. clin cardiol. 2022;45(4):359-69. 46. kontos mc, kurz mc, roberts cs, joyner se, kreisa l, ornato jp, et al. an evaluation of the accuracy of emergency physician activation of the cardiac catheterization laboratory for patients with suspected st-segment elevation myocardial infarction. ann emerg med. 2010;55(5):42330. 47. mccabe jm, armstrong ej, kulkarni a, hoffmayer ks, bhave pd, garg s, et al. prevalence and factors associated with false-positive st-segment elevation myocardial infarction diagnoses at primary percutaneous coronary intervention–capable centers: a report from the activatesf registry. arch intern med. 2012;172(11):864-71. 48. meyers hp, bracey a, lee d, lichtenheld a, li wj, singer dd, et al. accuracy of omi ecg findings versus stemi criteria for diagnosis of acute coronary occlusion myocardial infarction. int j cardiol heart vasc. 2021;33:100767. 49. aslanger ek, meyers hp, smith sw. time for a new paradigm shift in myocardial infarction. anatol j cardiol. 2021;25(3):156. 50. phibbs b, nelson w. differential classification of acute myocardial infarction into st-and non-st segment elevation is not valid or rational. ann noninvasive electrocardiol. 2010;15(3):191-9. 51. tziakas d, chalikias g, al-lamee r, kaski jc. total coronary occlusion in non st elevation myocardial infarction: time to change our practice? int j cardiol. 2021;329:1-8. 52. widimský p, rokyta r, št j, bělohlávek j, červinka p, kala p, et al. acute coronary syndromes with ongoing myocardial ischemia (acs with omi) versus acute coronary syndromes without ongoing ischemia (acs without omi): the new classification of acute coronary syndromes should replace old classification based on st segment elevation presence or absence—expert consensus statement of the czech society of cardiology. cor vasa. 2013;55(3):e225-e7. 53. meyers hp, weingart sd, smith sw. the omi manifesto dr smith’s ecg blog available from: http://hqmededecgblogspotcom/2018/04/the-omi-manifestohtml [internet]. [cited 22 august 2022]. 54. aslanger ek, yıldırımtürk ö, şimşek b, bozbeyoğlu e, şimşek ma, karabay cy, et al. diagnostic accuracy of electrocardiogram for acute coronary occlusion resulting in myocardial infarction (difoccult study). int j cardiol heart vasc. 2020;30:100603. 55. wereski r, chapman ar, lee kk, smith sw, lowe dj, gray a, et al. high-sensitivity cardiac troponin concentrations at presentation in patients with stsegment elevation myocardial infarction. jama cardiol. 2020;5(11):1302-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e78 table 1: studies showing the frequency of acute total coronary occlusion (ato) and cardiovascular outcomes in non-st-segment elevation myocardial infarction (nstemi) patients compared with nstemi patients without ato study year ato definition (timi flow grade) frequency of ato in nstemi cardiovascular outcomes (ato vs. non-ato) morawska et al. (5)observational study 2021 0 34.6% (138/399) -in-hospital mortality: (2.8% vs. 1.1%, p=0.007) -1-year mortality: (18.1% vs. 6.5%, p<0.001) fernando et al. (7)observational study 2021 0 14% (954/6829) -30-day mace: (6.7% vs. 3.8%, p<0.001) -4.9-years mortality: (12% vs. 18%, p<0.01) terlecki et al. (4)observational study 2021 0 19.9% (16209/81415) -c.a. before admission (3.09% vs. 2.19%, p<0.0001) -killip iv on admission: (2.48% vs. 1.69%, p<0.0001) -death during pci: (0.97% vs. 0.43%, p<0.0001) -timi flow 3 after pci: (83.36% vs. 88.61%, p<0.0001) ayad et al. (6)observational study 2021 0 22.4% (112/500) -in-hospital macce: (5.3% vs. 1%, p=0.07) -6-month macce: (5.4% vs. 4.6%, p=0.24) hung et al. (3)-metaanalysis 2018 -in 21 studies: 0-1 -in 3 studies: 0 -in 1 study: 0-2 34% (95% ci 30%-37%) average proportion -death rate: (or 1.72, 95% ci 1.49-1.98, p<0.001) -recurrent mi: (or 1.7, 95% ci 1.06-2.75, p=0.029) -cardiogenic shock: (or 1.66, 95% ci 1.35-2.04, p<0.001) khan et al. (2)-metaanalysis 2017 0-1 25.5% (10415/40777) -short-term mace: (rr 1.41, ci 1.17-1.70, p=0.0003) -mediumto long-term mace: (rr 1.32, ci 1.11-1.56, p=0.001) -short-term all-cause mortality: (rr 1.67, ci 1.31-2.13, p<0.0001) -mediumto long-term all-cause mortality: (rr 1.42, ci 1.08-1.86, p=0.01) ci: confidence interval; timi: thrombolysis in myocardial infarction, mace: major adverse cardiac events, c.a: cardiac arrest, pci: percutaneous intervention, macce: major adverse cardiac and cerebrovascular events, mi: myocardial infarction; or: odds ratio; rr: relative risk. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 10 table 2: high risk electrocardiogram (ecg) patterns associated with acute total coronary occlusion (ato) high risk ecg pattern criteria for diagnosis of ato sensitivity/specificity culprit artery hyperacute t waves (10, 12, 13) “bulky”, fat, wide, and often also tall and symmetric t-waves, such that the area under the curve, compared to the qrs amplitude, is large -a combination of: •j point/t wave > 25% •t wave/qrs > 75% •j point > 0.30 mv and •age > 45 years old 61.9%/98% lad, lcx or rca lbbb (15, 16) -smith’s modified sgarbossa criteria: •ste ≥1 mm concordant with qrs in any lead or •std≥1 mm in any of v1-v3 or •ste/s wave ≥ 25% in any lead 80%/99% lad, lcx or rca rv paced rhythm (17) -smith’s modified sgarbossa criteria: •ste ≥1 mm concordant with qrs or •std≥1mm in any of v1-v6 or •ste/s wave ≥ 25% in any lead 86%/83% lad, lcx or rca new rbbb ± lah (18) rbbb diagnostic criteria -any ste is suspicious proximal lad de winter’s pattern (22) 1-2 mm ste in avr and: •hyperacute t waves in v1-v6 •upsloping std 1-3 mm in v1-v6 proximal lad wellens’ syndrome (19, 20) -isoelectric or < 1mm elevated j point in a post-anginal period plus: •biphasic t waves in v2-v3 (pattern a) or •deeply inverted and symmetric t waves in v2-v3 (pattern b) •t wave changes may extend to v1, v4, v5, v6 69%/89% proximal lad diffuse std (26) -std > 1mm in ≥ 6 leads and: •ste in avr and/or v1 lm or severe 3 vessel disease aslanger’s pattern (25) -any ste in iii, but not in other inferior leads, with reciprocal std in avl plus: •std in any of v4-v6 but not in v2 with positive t wave •ste in v1 higher than in v2 lcx or rca and 2 or 3 vessel disease n wave sign (24) -notch or deflection in the terminal qrs complex ≥2 mm in ii, iii and avf and/or i, avl plus •continuous change of the notch ≥2 mm in ≥ 2 leads in 24 hours •prolonged qrs in these leads 77%/89% and 53%/97% / or 64%/96% lcx acute posterior omi (23) -std of any amplitude maximal in leads v1-v4 versus v5-v6 37.4%/97.6% lcx subtle stemi (27) -ste 0.1-1 mm combined with reciprocal std ≥0.5 mm lcx, rca or lad lad: left anterior descending artery, lcx: left circumflex artery, rca: right coronary artery, lbbb: left bundle branch block, ste: st-segment elevation, std: st-segment depression, rv: right ventricular, rbbb: right bundle branch block, lah: left anterior hemiblock, lm: left main coronary artery, omi: occlusion myocardial infarction; stemi: st-segment elevation myocardial infarction; avr: augmented vector right; avl: augmented vector left. table 3: electrocardiogram (ecg)patterns with normal, baseline st-segment elevation (ste) and proposed criteria to differentiate ste due to occlusion myocardial infraction (omi)) ecg pattern criteria for diagnosis of ato sensitivity/specificity culprit artery nv-ste (“early repolarization”) -4-variable formula: •0.052xqtc – 0.151xqrsv2-0.268xrv4 + 1.062xste60v3 ≥ 18.2 88.8%/94.7% lad (10, 29, 31) -terminal qrs distortion: •absence of both an s and j wave in either v2 or v3 20%/100% left ventricular aneurysm (32, 33) -any v1-v4 t /qrs ≥ 0.36 91.5%/81.3% lad ato: acute total coronary occlusion; nv-ste: normal variant st-elevation; qtc: bazett-corrected qt segment; qrsv2: qrs voltage in lead v2, rv4: r wave amplitude in lead v4; ste60v3: st-segment elevation in lead v3 60ms after j point; lad: left anterior descending artery. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2022; 10(1): e78 table 4: frequency of 7 findings among 146 patients with occlusion myocardial infarction (omi), identified by expert earlier than by criteria/angiogram feature frequency hyperacute t waves 49% pathologic q waves, along with subtle ste 47% terminal qrs distortion 53% reciprocal std and/or reciprocal t-wave inversion 82% subtle ste not meeting criteria, but with other features 83% any amount of std maximal in v1-v4 45% any ste in inferior leads with any std/t-wave inversion in avl 50% ste: st-segment elevation; std: st-segment depression; avl: augmented vector left. figure 1: flow diagram of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. avdikos et al. 12 figure 2: electrocardiogram (ecg) recordings from two male patients in their early 30s presenting with acute chest pain. ecg (a) is from a patient with de winter’s pattern and ecg (b) is consistent with “early repolarization”. ecg (a) does not meet stemi criteria but catheter laboratory was activated emergently and a total occluded left anterior descending artery was identified on the coronary angiogram and was stented successfully. ecg (b) satisfies current stemi criteria but emergent treatment was not required. serial unchanged ecg recordings with normal values of troponin and normal echocardiogram ruled out acute coronary syndrome. ecg (a) is reproduced after permission from dr. smith’s ecg blog. available from: https://hqmeded-ecg.blogspot.com/2021/03/de-winters-t-waves-are-not-stable-ecg.html, courtesy of stephen w. smith, md. figure 3: proposed evolution of acute coronary syndrome classifications. mi: myocardial infarction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods findings conclusion declarations references emergency. 2017; 5 (1): e82 http://dx.doi.org/10.22037/emergency.v5i1.18894 or i g i n a l re s e a rc h intravenous lidocaine compared to fentanyl in renal colic pain management; a randomized clinical trial hassan motamed1, mohammadreza maleki verki1∗ 1. emergency medicine department, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: september 2017; accepted: october 2017; published online: 23 october 2017 abstract: introduction: using alpha blockers such as intravenous (iv ) lidocaine has been deemed effective in controlling acute pain. therefore, the current study was designed with the aim of evaluating the efficiency of iv lidocaine in comparison to iv fentanyl in pain management of patients with renal colic in emergency department (ed). methods: in this double blind clinical trial, 18-65 year old patients that presented to ed with colicky flank pain and met the inclusion criteria of the study were allocated to either lidocaine or fentanyl group using block randomization and compared regarding pain severity 5, 10, 15, and 30 minutes after drug administration. results: 90 patients with the mean age of 35.75±8.87 years were divided into 2 groups of 45 (90% male). the 2 groups were not significantly different regarding the studied baseline variables. pain severity was not significantly different between the 2 groups at various times after injection. treatment failure rate 15 minutes after injection was 44.4% (20 cases) in iv lidocaine and 17.8% (8 cases) in iv fentanyl group (p = 0.006). these rates were 26.6% (12 patients) versus 22.2% 30 minutes after injection (p = 0.624). absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% ci: 8.3-44.9) in the 15th minute and 4.4 (95% ci: 13.3-22.2) 30 minutes after injection. number needed to harm (nnh) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% ci: 2.2-12.0) and 23, respectively. conclusion: although mean pain severity was not significantly different between iv fentanyl and lidocaine at various times after injection, treatment failure rate was significantly higher in the iv lidocaine group 15 minutes after injection. keywords: fentanyl; lidocaine; renal colic; pain management; analgesia; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: motamed h, maleki verki m. intravenous lidocaine compared to fentanyl in renal colic pain management; a randomized clinical trial. emergency. 2017; 5(1): e82. 1. introduction r renal colic is one of the most common clinical manifestations of a stone being present in the urinary system, which presents as sudden and severe flank pain (1). in the united states, the prevalence of renal colic has increased from 5.2% during 1994-1998 to 8.8% in 2007-2010 (2, 3). one of the major duties of emergency department (ed) is reducing patients’ pain and suffering before taking any treatment or surgical measures. recently, using alpha blockers such as intravenous (iv ) lidocaine, nifedipine and nerve blockers in the intercostal area has been deemed effective in reducing renal colic pain (4-6). when narcotic drugs lack the required effectiveness and lead ∗corresponding author: mohammadreza maleki verki; emergency department, golestan hospital, ahvaz, iran. tel: 00989122782787 email: drmalaki676@yahoo.com to undesirable side effects, lidocaine can be a good choice. iv lidocaine has been deemed effective in controlling neuropathic pains such as diabetic neuropathy, post-surgery pains, bone fracture pain, headache and nervous system malignancies (7-10). continuous infusion of iv lidocaine during and after abdominal surgery has accelerated patient recovery and reduced length of hospital stay (11). using opioids has some dangers due to reasons such as inhibition of respiratory center in medulla region and activation of vomiting center (12). these drugs are used as an appropriate analgesic in ed either alone or along with midazolam (13). finding an effective analgesic with minimal side effects has been continuously desired by the physicians involved with these patients. therefore, the current study was designed with the aim of evaluating the efficiency of iv lidocaine in comparison to iv fentanyl in pain management of patients with renal colic. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. motamed and m. maleki verki 2 2. methods 2.1. study design and setting in this double blind clinical trial, the effectiveness of iv lidocaine and iv fentanyl was evaluated and compared in pain management of patients with renal colic admitted to ed of golestan hospital, ahwaz, iran, in 2015. the study was approved by the ethics committee of ahwaz university of medical sciences under the number “ajums.rec.1392.324” and the researchers adhered to all the principles stated in the declaration of helsinki regarding ethical practice and confidentiality of patient data. informed consent was obtained from all the participants for taking part in the study. all the expenses of patients’ treatment were covered by the project executive and no additional fees were inflicted upon the patients. this study was registered on the iranian registry of clinical trials under the number irct2017081415446n12. 2.2. participants patients in the 18-65 years age range that had presented to the ed with colicky flank pain and lacked histories such as: cardiac dysrhythmia and ischemia, parenchymal tissue problems in liver and kidney, and history of using mono amino oxidase (mao) inhibitor drugs in the last 2 weeks, were included in the study. in addition, patients with a history of allergy to morphine or other opiates, definite or possible pregnancy, lactating women, addiction to opiates, and receiving analgesics in the last 6 hours were excluded from the study. to confirm absence of dysrhythmia or underlying ischemic disease, electrocardiogram was used on admission. all the clinical examinations were done by 2 physicians, one senior resident of emergency medicine and one senior resident of urology. clinical diagnoses were confirmed by performing ultrasonography or spiral computed tomography (ct) scan, or presence of hematuria in urinalysis after management of the patient’s pain and those who did not have definitive evidence of stone in evaluations were excluded from the study. 2.3. intervention patients were allocated to a group receiving either lidocaine (1.5 mg/kg) or fentanyl (1.5 µg/kg) via block randomization. drug prescriptions were as iv infusion during 2 minutes while patients were under cardiac monitoring. for patients who still had moderate to severe pain 30 minutes after injection, morphine sulfate with the standard dose of 0.1 mg/kg was prescribed as additional analgesic. the physician prescribing the drug and the patient were blind to the prescribed drug. drugs were prepared by a nurse in syringes with the same volume and color in the absence of the physician and were then given to the physician. figure 1: comparison of pain severity between the 2 studied groups 5 (p = 0.113), 10 (p = 0.056), 15 (p = 0.137) and 30 (p = 0.291) minutes after drug injection. 2.4. outcome the primary outcome of this study was evaluating the pain score of patients based on visual analog pain scale (vas) 5, 10, 15, and 30 minutes after injection. 3 points pain reduction based on vas was considered as clinically significant pain reduction. therefore, lack of 3 points pain reduction 15 and 30 minutes after injection were considered as treatment failure. 2.5. data gathering demographic data (age, sex, weight) and data regarding pain severity on admission to ed and 5, 10, 15, and 30 minutes after injection were gathered using a checklist. the senior emergency medicine resident was responsible for data gathering and was blind to the drug received by the patient. 2.6. statistical analysis sample size was estimated to be 40 for each group considering 95% confidence interval and type 2 error of 0.2% (4). data analysis was done using spss 21 software. quantitative data were reported based on mean ± standard deviation and qualitative ones based on frequency and percentage. chi square test, fisher’s exact test and t-test were used for comparisons. p values less than 0.05 were considered significant. 3. results 3.1. baseline characteristics 90 patients with the mean age of 35.75±8.87 years (20-55) were randomly divided into 2 groups of iv lidocaine (45 patients) and iv fentanyl (45 patients) (90% male). table 1 has compared the baseline characteristics of the 2 groups. as can be seen, the 2 groups are not significantly different regarding studied baseline variables. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e82 table 1: comparison of baseline characteristics between the 2 studied groups variable iv fentanyl iv lidocaine p value sex male 39 (86.7) 42 (93.3) 0.292 female 6 (13.3) 3 (6.7) age (year) 39.08 ± 6.64 34.08 ± 9.49 0.112 weight (kg) 80.93 ± 15.27 82.85 ± 15.83 0.572 pain severity on admission moderate 2 (4.4) 2 (4.4) 1.000 severe 43 (95.6) 43 (95.6) data are presented as frequency (%) or mean ± standard deviation. iv: intravenous. table 2: comparison of pain severity between the 2 studied groups at various times after drug injection time iv fentanyl iv lidocaine p value 5 minutes mild 8 (17.8) 7 (15.6) 0.302 moderate 17 (37.8) 11 (24.4) severe 20 (44.4) 27 (60.0) 10 minutes mild 14 (31.1) 11 (24.4) 0.310 moderate 18 (40.0) 14 (31.1) severe 13 (28.9) 20 (44.4) 15 minutes mild 20 (44.4) 14 (31.1) 0.405 moderate 14 (31.1) 16 (35.6) severe 11 (24.4) 15 (33.3) 30 minutes mild 25 (55.6) 22 (48.9) 0.679 moderate 7 (15.6) 10 (22.2) severe 13 (28.9) 13 (28.9) data are presented as frequency (%). iv: intravenous. 3.2. pain management table 2 and figure 1 compare pain severity between the 2 groups 5, 10, 15, and 30 minutes after drug injection. pain severity was not significantly different between the 2 groups at various times after injection. treatment failure rate 15 minutes after injection was 44.4% (20 cases) in iv lidocaine and 17.8% (8 cases) in iv fentanyl group (p = 0.006). these rates were 26.6% (12 cases) versus 22.2% (10 cases), 30 minutes after injection (p = 0.624). therefore, the absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% ci: 8.3-44.9) in the 15th minute and 4.4 (95% ci: 13.3-22.2) 30 minutes after injection. number needed to harm (nnh) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% ci: 2.2-12.0) and 23, respectively. 4. discussion based on the findings of the present study, although mean pain severity was not significantly different between iv fentanyl and iv lidocaine groups at various times after injection, treatment failure rate was significantly higher in the lidocaine group 15 minutes after injection. in addition, the absolute risk increase of treatment failure in case of using lidocaine 15 and 30 minutes after injection were 26.7 and 4.4 percent, respectively. renal colic is caused due to increased pressure in the upper urinary tract or dilatation of kidney capsule following urinary retention. in a study by khaniha et al. on evaluating the effect of various drugs in relieving renal colic, the results showed that pethidine 10 to 45 minutes after injection, methadone 30-60 minutes and morphine 1.5 to 30 minutes after injection showed their analgesic effects (14). using intranasal fentanyl led to an effective sedation in pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. motamed and m. maleki verki 4 tients 30 minutes after administration (15). in another study that had compared the effectiveness of lidocaine and morphine, the findings showed that lidocaine is a safe, effective and cheap method for induction of analgesia in patients with renal colic compared to morphine, which lacks the side effects of morphine such as nausea and vomiting. time needed for induction of analgesia when using morphine alone and morphine with lidocaine were reported to be 100 and 87 minutes after injection, respectively (16). in another study, 240 patients aged 18 to 65 years presenting to imam reza hospital, tabriz, iran, with renal colic were randomly divided into 2 groups receiving either iv morphine or iv lidocaine. the results indicated effectiveness of iv lidocaine in comparison to morphine (4). based on the results of this study, it seems that iv lidocaine has proper ability in controlling renal colic during 30 minutes. however, if the speed of analgesia induction is of higher priority for the physician and patient compared to probable side effects, considering the high rate of treatment failure of iv lidocaine in 15 minutes (44.4% vs 17.8% for fentanyl), it cannot be a good choice for this purpose. 5. limitation stone size, history of kidney stone, and ethnic characteristics were not evaluated in this study, but they may affect pain severity and response to analgesics used. 6. conclusion the absolute risk increase of renal colic management failure with iv lidocaine 15 and 30 minutes after injection were 26.7 and 4.4, respectively. it seems that iv lidocaine cannot be a good choice when quick pain control is of higher priority for the physician. 7. appendix 7.1. acknowledgements all staffs who helped to establish the trial, are acknowledged. 7.2. author contribution all the authors met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. 7.3. funding/support no funds have been received for doing this project. 7.4. conflict of interest hereby the authors declare that there is no conflict of interest regarding the present study. references 1. edwards j, sloan e, eder s, chan s. renal colic patient pain management in the emergency department. annals of emergency medicine. 2004;44(4):s58. 2. stamatelou kk, francis me, jones ca, nyberg lm, curhan gc. time trends in reported prevalence of kidney stones in the united states: 1976–1994. kidney international. 2003;63(5):1817-23. 3. scales cd, smith ac, hanley jm, saigal cs, project udia. prevalence of kidney stones in the united states. european urology. 2012;62(1):160-5. 4. soleimanpour h, hassanzadeh k, vaezi h, golzari se, esfanjani rm, soleimanpour m. effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. bmc urology. 2012;12(1):13. 5. dellabella m, milanese g, muzzonigro g. randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi. the journal of urology. 2005;174(1):16772. 6. iguchi m, katoh y, koike h, hayashi t, nakamura m. randomized trial of trigger point injection for renal colic. international journal of urology. 2002;9(9):475-9. 7. barzegari h, motamed h, ziapour b, hajimohammadi m, kadkhodazadeh m. intranasal lidocaine for primary headache management in emergency department; a clinical trial. emergency. 2017;5(1):e79. 8. ferrini r, paice j. how to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. the journal of supportive oncology. 2004;2(1):90. 9. afhami m, salmasi p. studying analgesic effect of preincisional infiltration of lidocaine as a local anesthetic with different concentrations on postoperative pain. pak j med sci. 2009;25(5):821-4. 10. forouzan a, barzegari h, motamed h, khavanin a, shiri h. intravenous lidocaine versus morphine sulfate in pain management for extremity fractures; a clinical trial. emergency. 2017;5(1):e68. 11. marret e, rolin m, beaussier m, bonnet f. meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. british journal of surgery. 2008;95(11):1331-8. 12. ockerblad nf, carlson he, simon jf. the effect of morphine upon the human ureter. the journal of urology. 1935;33(4):356-62. 13. marx j, walls r, hockberger r. rosen’s emergency medicine-concepts and clinical practice e-book: elsevier health sciences; 2013. 14. khaniha rb, safarinezhad mr, markazi moghadam n, valimanesh ha, abd elahian m. the comparison of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e82 efficacy of common pain management in acute renal colic. annals of military and health sciences research 2004;2(3):381-6. 15. belkouch a, zidouh s, rafai m, chouaib n, sirbou r, elbouti a, et al. does intranasal fentanyl provide efficient analgesia for renal colic in adults? the pan african medical journal. 2015;20. 16. firouzian a, alipour a, dezfouli hr, kiasari az, baradari ag, zeydi ae, et al. does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ed with acute renal colic? a double-blind, randomized controlled trial. the american journal of emergency medicine. 2016;34(3):443-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 170 emergency (2015); 3 (4): 170-171 educational evidence based emergency medicine part 3: positive and negative likelihood ratios of diagnostic tests alireza baratloo1, saeed safari1, mohamed elfil2, ahmed negida3* 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. faculty of medicine, alexandria university, alexandria, egypt. 3. faculty of medicine, zagazig university, zagazig, egypt. *corresponding author: ahmed negida; faculty of medicine, zagazig university, el-kanayat, el-sharkia, zagazig, egypt. tel: +201125549087; email: ahmed01251@medicine.zu.edu.eg received: july 2015; accepted: august 2015 introduction: n the previous two parts of educational manuscript series in emergency, we explained some screening characteristics of diagnostic tests including accuracy, sensitivity, specificity, and positive and negative predictive values (1, 2). in the 3rd part we aimed to explain positive and negative likelihood ratio (lr) as one of the most reliable performance measures of a diagnostic test (3). to better understand this characteristic of a test, it is first necessary to fully understand the concept of sensitivity and specificity. so we strongly advise you to review the 1st part of this series again (1, 2). in short, the likelihood ratios are about the percentage of people with and without a disease but having the same test result (4). the prevalence of a disease can directly influence screening characteristics of a diagnostic test, especially its sensitivity and specificity. trying to eliminate this effect, lr was developed. pre-test probability of a disease multiplied by positive or negative lr can estimate posttest probability. therefore, lr is the most important characteristic of a test to rule out or rule in a diagnosis. a positive likelihood ratio > 1 means higher probability of the disease to be present in a patient with a positive test. the further from 1, either higher or lower, the stronger the evidence to rule in or rule out the disease, respectively (5). it is obvious that tests with lr close to one are less practical. on the other hand, lr further from one will have more value for application in medicine. usually tests with lr < 0.1 or > 10 are considered suitable for implication in routine practice. calculation: positive likelihood ratio (lr+): it is the ratio of probability of a patient with a disease and having positive test result divided by probability of a patient without a disease but having positive test result (5). it can be directly calculated from this equation: 𝑳𝑹+= 𝐬𝐞𝐧𝐬𝐢𝐭𝐢𝐯𝐢𝐭𝐲 𝟏 − 𝐬𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲 example 1: imagine that there is a diagnostic test, which has sensitivity and specificity of 80% and 60%, respectively. in this scenario, the positive likelihood ratio of this test will be calculated as follows: lr+ = 0.80/ (1-0.60) = 0.80/ 0.40 = 2 negative likelihood ratio (lr −): it is the ratio of probability of a patient with a disease but having negative test result divided by probability of a patient without a disease and having negative test result (5). it can be directly calculated from this equation: 𝑳𝑹−= 𝟏 − 𝐬𝐞𝐧𝐬𝐢𝐭𝐢𝐯𝐢𝐭𝐲 𝐬𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲 example 2: imagine that we have a diagnostic test with sensitivity and specificity of 90% and 70%, respectively. in this case, the negative likelihood ratio is calculated as follows: lr − = (1-0.9)/ 0.7 = 0.1/0.7 = 0.14 example 3: in the study by aminiahidashti et al., the sensitivity and the specificity of the ascites fluid appearance as a diagnostic test for the detection of spontaneous bacterial peritonitis were 46.9% and 87.5%, respectively (6). so, positive and negative likelihood ratios of this test can be calculated as follows: lr + = 46.9 % / (1 87.5%) = 0.469 / (10.875) = 0.469 / 0.125 = 3.8 lr − = (10.469) / 0.857 = 0.531 / 0.875 = 0.6 example 4: in taghizadieh et al. study, chest x-ray in diagnosis of pleural effusion had sensitivity and specificity of 66.7% and 77.8%, respectively (7). given this data, the lr + and lr – can be calculated as follows: lr + = 0.667/ (1-0.778) = 0.667/ 0. 222 = 3 lr − = (1-0.667)/ 0.778 = 0.333/ 0.778 = 0.4 i this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 171 baratloo et al references: 1. safari s, baratloo a, elfil m, negida as. part 2: positive and negative predictive values of diagnostic tests. emergency. 2015;3(3):87-8. 2. baratloo a, hosseini m, negida a, el ashal g. part 1: simple definition and calculation of accuracy, sensitivity and specificity. emergency. 2015;3(2):48-9. 3. mcgee s. simplifying likelihood ratios. j gen intern med. 2002;17(8):647-50. 4. grimes da, schulz kf. refining clinical diagnosis with likelihood ratios. lancet. 2005;365(9469):1500-5. 5. deeks jj, altman dg. diagnostic tests 4: likelihood ratios. bmj. 2004;329(7458):168-9. 6. aminiahidashti h, hosseininejad sm, montazer h, bozorgi f, jahanian f, raee b. diagnostic accuracy of ascites fluid gross appearance in detection of spontaneous bacterial peritonitis. emergency. 2014;2(3):138-40. 7. taghizadieh a, ala a, rahmani f, nadi a. diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report. emergency. 2015;3(3):114-6. introduction: calculation: positive likelihood ratio (lr+): it is the ratio of probability of a patient with a disease and having positive test result divided by probability of a patient without a disease but having positive test result (5). it can be directly calculated from this equation: negative likelihood ratio (lr −): references: emergency. 2017; 5 (1): e66 or i g i n a l re s e a rc h quick stick for identifying traumatic patients in need of tetanus prophylaxis; a diagnostic accuracy study iraj golikhatir1, seyed hossein montazer1∗, nabiollah bagheri1, fatemeh jahanian1, farzad bozorgi1, seyed mohammad hosseininejad1, hamed amini ahidashti1 1. emergency department, imam khomeini hospital, mazandaran university of medical sciences, sari, iran. received: march 2017; accepted: april 2017; published online: 30 april 2017 abstract: introduction: based on the existing studies, measuring serum level of immunoglobulin for making decisions regarding prescription of tetanus prophylaxis seems logical and cost effective. therefore, the present study was done with the aim of evaluating the diagnostic accuracy of tetanus quick stick (tqs) in comparison with elisa method in this regard. methods: the present diagnostic accuracy study was carried out on trauma patients presenting to emergency department, who were in need of receiving tetanus prophylaxis due to dirty wounds or injuries. patients’ blood was evaluated regarding presence of anti-tetanus antibody via tqs and elisa methods and screening performance characteristics of tqs in identifying the cases in need of receiving prophylaxis was calculated compared to elisa as the reference test. results: 148 patients with the mean age of 34.58 ± 15.86 years (4-86) were studied (87.8% male). agreement rate between the results of tqs and elisa was 0.78 based on calculation of kappa coefficient. sensitivity, specificity and area under the roc curve of tqs were estimated to be 100 (95% ci: 96.50 – 100), 66.66 (95% ci: 38.68 – 86.01), and 0.83 (95% ci: 0.68 – 0.98), respectively. if tqs was used, the cost of treatment regarding use of tetabulin could have a 91.7% reduction. conclusion: based on the findings of the present study, tqs has good diagnostic accuracy in comparison with elisa and considering its 100% sensitivity and negative predictive value in cases with dirty wound, it can be considered as a reliable tool for screening patients that do not need to receive anti-tetanus prophylaxis. keywords: tetanus; point-of-care testing; enzyme-linked immunosorbent assay; immunoglobulins; prevention and control; wounds and injuries; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: golikhatir i, montazer sh, bagheri n, jahanian f, bozorgi f, hosseininejad sm, amini ahidashti h. quick stick for identifying traumatic patients in need of tetanus prophylaxis; a diagnostic accuracy study. emergency. 2017; 5(1): e66. 1. introduction t etanus manifests in all age groups and geographical areas after a wound comes into contact with anaerobic gram positive bacteria called clostridium tetani (1-7). the risk of developing the disease is higher in hot and humid areas, injecting drug addicts, people who have not been vaccinated, and those with a deficiency in their immune system. prevalence of tetanus in the developing countries is 135 times more than that of developed countries and its death rate has been estimated to be about 20% to 45% in those affected (8). currently, in many emergency departments (eds) making decisions regarding the need for tetanus ∗corresponding author: seyed hossein montazer; emergency department, imam khomeini hospital, amir mazandarani avenue, sari, mazandaran, iran. tel: 00989111114814 email: drgolikhatir@gmail.com prophylaxis prescription is done based on vaccination history and wound characteristics (9-11). however, noting that the patients do not provide reliable history regarding vaccination, using serum immunoglobulin level measurements for making decisions regarding prescription of tetanus prophylaxis seems to be more logical and cost effective (6, 1217). tetanus quick stick (tqs) is a tool for qualitative measurement of immunoglobulin via immunochromatographic assay and its use increases reliability of vaccination history (6, 15, 18). yet, various opinions exist regarding the screening performance characteristics of this test and its sensitivity and specificity have been estimated to be about 76 to 88% and 97 to 100%, respectively (6, 18, 19). the present study was done with the aim of evaluating the diagnostic accuracy of tqs in determining the condition of serum level of tetanus immunoglobulin in comparison to elisa method. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com i. golikhatir et al. 2 2. methods 2.1. study design the present diagnostic accuracy study was carried out on trauma patients presenting to ed of imam khomeini hospital, sari, mazandaran, iran, throughout the time between october 2015 and november 2016, who were in need of receiving tetanus prophylaxis due to wounds or injuries. protocol of this study was approved by the ethics committee of mazandaran university of medical sciences after evaluation in the research council of emergency medicine specialists group. to maintain confidentiality of patients’ medical profile data and adhering to ethical practice, the researchers keenly adhered to the principles introduced in the declaration of helsinki during the study period. information regarding the study method was given to the participants and written consent was obtained from them before being included in the study. no treatment intervention was done in the study and all the costs of the project were covered by the researchers. 2.2. participants trauma patients presenting to the mentioned ed with dirty wounds or injuries (tetanus prone), who needed tetanus prophylaxis were evaluated using non-probability convenience sampling during one year, until the required sample size was reached. patients with severely bleeding wounds, those in need of rapid care with surgery, and pregnant women were excluded from the study. in this study, a wound made more than 6 hours before, contaminated with soil or saliva, caused by puncture (nail going in), compression, bullet, burn, and frostbite were considered as dirty wound. complete vaccination was defined as history of more than 3 shots of tetanus vaccine and incomplete or undefined vaccination was history of 3 times or less injections. 2.3. data gathering a senior emergency medicine resident was responsible for gathering data of the patients by completing a pre-designed checklist including baseline characteristics (age, sex, vaccination history), type of prophylaxis prescribed in ed (tetabulin, vaccine, none) as well as results of patients’ serum evaluation regarding presence of anti-tetanus antibody using tqs and elisa. two separate individuals performed tqs test and elisa and were blind to the results of the other test. 2.4. tqs test method after gathering preliminary data, tqs test was done on the patient’s bedside by a trained nurse or physician in charge of the patient. a drop of blood from the patient’s fingertip was placed on the tqs kit (made in china) and 3 drops of the corresponding buffer was added to it. there were 2 marks on the kit, the c (control) and t (tetanus) lines. after adding the buffer, a maximum of 10 minutes was given for the lines to change color. in this kit color change of the c region indicated correct sampling and color change in the t region showed presence of tetanus antibody (in case of not being immune to tetanus, no color change will be seen in this region). no change of color in the c region indicated an error and in this case, the test was repeated with another kit. 2.5. elisa method elisa was used as the reference test to determine serum level of anti-tetanus igg. 2.5-3 cc of the patient’s venous blood was drawn by a trained technician and immediately sent to the laboratory. if the level of this antibody was higher than 0.5 iu/ml, immunity against tetanus was positive and there was no need for prophylaxis against it. if the antibody level was lower than 0.1 iu/ml, immunity to tetanus was negative and there was need for prophylaxis. 2.6. statistical analysis required sample size for performing the present study considering the 74.1% prevalence of immunity to tetanus, type 1 error of 5%, type 2 error of 10%, and need for immunity of 56.9% was calculated to be 148 cases (12). data were statistically analyzed using spss 21 statistical software. for reporting quantitative variables, mean and standard deviation (sd) were used and for qualitative variables, frequency and percentage were reported. to evaluate correlation and agreement rates, pearson’s correlation test and kappa coefficient were applied. screening performance characteristics of tqs test including sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were calculated with 95% confidence interval (ci) via medical calculator. calculation of the area under the receiver operating characteristic (roc) curve was performed for assessing the diagnostic accuracy of tqs test. in this study, pvalue less than 0.05 was considered as level of significance and elisa was used as the reference test. 3. results 148 patients with the mean age of 34.58 ± 15.86 years (486) were studied (87.8% male). table 1 shows the baseline characteristics of the participants. based on the findings of the tqs test, 10 (6.8%) patients had a negative serum antitetabulin antibody, while the number was 15 (10.1%) according to elisa. tetabulin was prescribed for all but 30 (20.27%) patients. the rate of overlap between results of tqs and elisa with the patients’ history regarding complete vaccination were (r =30, p < 0.001) and (r = 0.32, p < 0.001), respectively. in addition, agreement rate between the results of tqs and elisa was 0.78 (p < 0.001) based on calculation of kappa this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e66 table 1: baseline characteristics of the studied patients variable frequency (%) age (year) < 20 16 (10.8) 20 – 40 87 (58.8) 40 – 60 30 (20.3) ≥ 60 15 (10.1) sex male 130 (87.8) female 18 (12.2) vaccination history complete 82 (55.4) incomplete 66 (44.6) tqs∗ result positive 138 (93.2) negative 10 (6.8) elisa result positive 133 (89.9) negative 15 (10.1) received immunoglobulin yes 118 (79.73) no 30 (20.27) ∗tqs: tetanus quick stick. table 2: screening performance characteristics of tetanus quick stick (tqs) versus elisa test in detection of patients with negative serum anti-tetanus igg characteristics tqs (95 % ci) true positive* 133 true negative 10 false positive 0 false negative 5 sensitivity 100 (96.50 – 100.00) specificity 66.66 (38.68 – 87.01) positive predictive value 96.37 (91.31 – 98.65) negative predictive value 100 (65.54 – 100.00) positive likelihood ratio 26.60 (11.24 – 62.93) negative likelihood ratio 0 (0 – nan) ∗ regarding existence of anti-tetanus immunoglobulin; nan: the calculation cannot be performed. coefficient. table 2 depicts the screening performance characteristics of tqs test compared to elisa as the reference test. area under the roc curve of tqs for determining the serum level of anti-tetanus immunoglobulin was 0.83 (95% ci: 0.68 âăş 0.98) compared to elisa (figure 1). treatment cost in this study, the cost of injecting immunoglobulin for 118 patients was 1355.41 dollars since the cost of each tetabulin ampoule is about 11.49 dollars. considering the true positive test results of tqs (91.7% of the cases), this cost could be reduced to 112.50 dollars, which would save 1242.91 dollars of the treatment expenses. figure 1: area under the receiver operative characteristic (roc) curve of tetanus quick stick in detection of patients with negative serum anti-tetanus igg. 4. discussion: based on the findings of the present study, tqs has good (83%) diagnostic accuracy in comparison with elisa and considering its 100% sensitivity and negative predictive value in cases with dirty wound, it can be considered as a reliable tool for screening patients that do not need to receive antitetanus prophylaxis. however, considering the 66.6% specificity, it cannot be used as a confirming tool for rule in purposes. since being affected with the severe form of tetanus is accompanied by a high mortality rate, prophylaxis prescription for stopping the patients from being affected is very important and using tools that help identify patients in need of receiving prophylaxis can be of great help (3, 20). results of a study on hospitalized children 1 – 9 years of age in nigeria showed that the protective serologic level of anti-tetanus immunoglobulin using tqs and elisa was estimated to be 45.4 and 44.7, respectively. in the study, it was shown that lack of a recent history of receiving a tetanus vaccine shot was associated with a high chance of nonprotective levels of immunity. a good conformity existed between the results of elisa and tqs and tqs test had 95.7% sensitivity, 97.6% specificity, 98% positive predictive value and 96% negative predictive value (17). in a study aiming to determine the sensitivity and specificity of tqs as a rapid test that can be used for evaluation of the immunity condition against tetanus, it was shown that this test had a sensitivity of 88.1% and specificity of 97.6%. in addition, using this test significantly reduced the treatment costs (18). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com i. golikhatir et al. 4 another study on 988 patients to compare the screening performance characteristics of tqs and elisa revealed 76.7% sensitivity and 98% sensitivity for tqs. overall, this study concluded that using this test in emergency settings would lead to more accurate assessments in tetanus prevention (6). in another study it was shown that the positive predictive value and specificity of tqs are 100% when compared with elisa (19). in the study by stubbe et al. in belgium to improve tetanus prophylaxis in ed it was depicted that tqs is a practical tool in ed, which significantly reduces the costs. in fact using tqs led to improved management in 56.9% patients by avoiding unnecessary treatments (14). comparing tqs and clinical decisions based on vaccination history and wound type in 1658000 adult patients in 2014 indicated that using tqs is an effective and low-cost method compared to medical interview, especially in patients over the age of 65 years with wounds prone to tetanus; however, this method is considered a costly method in patients with clean wounds (3). results of the present study concerning the screening performance characteristics of tqs for anti-tetanus immunoglobulin are in agreement with some of the above-mentioned studies and contradict with some. the cause of these controversies in the results obtained regarding the screening performance characteristics of this test could be summarized in a few categories. first, the manufacturing company of the tqs has not been the same in all the studies and therefore, the quality of the tool could have affected its screening performance characteristics. the second point is about the studied patients. it seems that screening performance characteristics of the test vary based on wound type (tetanus prone or not). this has been clearly confirmed in the study by n’diaye et al. in 2014 (3). in the present study, all the patients had a dirty wound and this might have caused the lower specificity estimated in this study compared to previously mentioned ones. the third point is about the reference tests in the mentioned studies, which is not the same in all of them. in some studies comparisons have been done with clinical decisions, while in others tqs has been compared with elisa, which can be another cause for differences in their findings. yet overall, what all the studies agree on unanimously is reduction in costs and better management of the patients in need of receiving tetanus prophylaxis in case of using tqs. availability, low cost and ability to do the test at the patient’s bedside are among its undeniable advantages. it seems that doing a review study and if possible, a meta-analysis for making the final decision regarding the screening performance characteristics of tqs is helpful. 5. limitations including patients with dirty wounds and exclusion of patients with clean wounds might have somehow caused a selection bias in the present study. intrinsic limitations of cross sectional studies are also another item worth mentioning in this regard. 6. conclusion based on the findings of the present study, tqs has good diagnostic accuracy in comparison with elisa and considering its 100% sensitivity and negative predictive value in cases with dirty wound, it can be considered as a reliable tool for screening patients that do not need to receive anti-tetanus prophylaxis. 7. appendix 7.1. acknowledgements this article is derived from a research plan titled “evaluating the diagnostic accuracy of tetanus quick stick in identifying trauma patients in need of receiving prophylaxis in emergency department”. we would like to thank and acknowledge the contribution of emergency department and laboratory staff who helped us in data gathering and executing the plan. 7.2. author contribution all the authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. yoon ys, kim ec, lee wh, chung sw, yi jh, park ic, et al. utility of tetanos quick stick (r) test for selective tetanus prophylaxis. journal of the korean society of emergency medicine. 2004;15(2):95-101. 2. cooke m. are current uk tetanus prophylaxis procedures for wound management optimal? emergency medicine journal. 2009;26(12):845-8. 3. n’diaye ds, schwarzinger m, obach d, poissy j, matheron s, casalino e, et al. effectiveness and cost of quick diagnostic tests to determine tetanus immunity in patients with a wound in french emergency departments. bmc infectious diseases. 2014;14(1):1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e66 4. borrow r, balmer p, roper mh. vbthe immunological basis for immunization series module 3: tetanus. 2007. 5. cavenaile j-c, gerard p, duchateau j. evaluation d’un test rapide immuno-chromatographique comme aide a la prophylaxie antitetanique dans un service d’urgences. immuno-analyse & biologie specialisee. 2012;27(4):18590. 6. colombet i, saguez c, sanson-le pors m-j, coudert b, chatellier g, espinoza p. diagnosis of tetanus immunization status: multicenter assessment of a rapid biological test. clinical and diagnostic laboratory immunology. 2005;12(9):1057-62. 7. elkharrat d, sanson-le-pors m, arrouy l, beauchet a, benhamou f. evaluation of a bedside immunotest to predict individual anti-tetanus seroprotection: a prospective concordance study of 1018 adults in an emergency department. emergency medicine journal. 2010;27(1):36-42. 8. derakhshanfar h, hashemi b, manouchehrifar m, kashani p, forouzanfar mm. knowledge of emergency medicine residents in relation to prevention of tetanus. emergency. 2014;2(2):71. 9. committee pf. bnf for children: 2012-2013: pharmaceutical press; 2012. 10. barrett t, lander a, diwakar v. a paediatric vade-mecum: crc press; 2002. 11. committee ia. immunisation guidelines for ireland. royal college of physicians of ireland. 2010. 12. organization wh. who position on measles vaccines. vaccine. 2009;27(52):7219-21. 13. roper mh, vandelaer jh, gasse fl. maternal and neonatal tetanus. the lancet. 2007;370(9603):1947-59. 14. stubbe m, mortelmans lj, desruelles d, swinnen r, vranckx m, brasseur e, et al. improving tetanus prophylaxis in 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in assessment of immunity status. the american journal of emergency medicine. 2011;29(7):717-20. 19. paulke-korinek m, rendi-wagner p, kundi m, tomann b, wiedermann u, kollaritsch h. pretravel consultation: rapid dipstick test as a decision guidance for the application of tetanus booster vaccinations. journal of travel medicine. 2008;15(6):437-41. 20. orsi g, modini c, principe m, di muzio m, moriconi a, amato m, et al. assessment of tetanus immunity status by tetanus quick stick and anamnesis: a prospective double blind study. ann ig. 2015;27(2):467-74. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion: limitations conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e50 rev i ew art i c l e heart versus grace score in predicting the outcomes of patients with acute coronary syndrome; a systematic review and meta-analysis ali kabiri1, pantea gharin1, seyed ali forouzannia2, koohyar ahmadzadeh1, reza miri3∗, mahmoud yousefifard3,1 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. department of medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran received: may 2023; accepted: june 2023; published online: 19 july 2023 abstract: introduction: several scoring systems have been proposed to predict the outcomes of patients with ischemic heart disease. global registry of acute coronary events (grace) and history, ecg, age, risk factors, and troponin (heart) scores are two of the more widely used risk prediction tools in patients with acute coronary syndrome (acs). the present systematic review and meta-analysis aimed to compare the value of grace and heart scores in the outcome prediction of acs patient. methods: the online databases of medline, embase, web of science, and scopus were search until september 2022 for articles directly comparing grace and heart scores value in prediction of outcome in patients with acs. grace score cut-offs were categorized into two groups of less than and equal to 100 and more than 100, and heart score cut-offs were categorized into three groups of less than 4, equal to 4, and more than 4. investigated outcomes were major adverse cardiovascular events (mace), acute myocardial infraction (ami) and all-cause mortality. results: 25 articles were included. the sensitivity and specificity of the grace score for prediction of mace were 0.96 and 0.26 for cut-offs of ≤ 100, and 0.58 and 0.69 for cut-offs of >100, respectively. the sensitivity and specificity of the heart score for prediction of mace were 0.99 and 0.16 for cut-offs less than 4, 0.93 and 0.47 for equal to 4, and 0.77 and 0.78 for cut-offs greater than 4. grace score was shown to be predictive of ami with sensitivity and specificity of 0.95 and 0.29, respectively. the analysis for the value of heart score in the prediction of ami a sensitivity and specificity of 0.94 and 0.48, respectively. the risk scores were not found to be suitable predictors of all-cause mortality. conclusion: the results demonstrated the low specificity of grace and heart scores in predicting the mace, ami and all-cause mortality, irrespective of the utilized cut-off. considering the acceptable sensitivity of two scores in predicting the mace and ami, these scores were more suitable to be used as a rule-out tool for identification of acs patients with low risk of developing adverse outcomes. keywords: acute coronary syndrome; risk assessment; sensitivity; specificity; decision tools cite this article as: kabiri a, gharin p, forouzannia sa, ahmadzadeh k, miri r, yousefifard m. heart versus grace score in predicting the outcomes of patients with acute coronary syndrome; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e50. https://doi.org/10.22037/aaem.v11i1.2001. ∗corresponding author: reza miri; prevention of cardiovascular disease research center, imam hossein hospital, madani avenue, tehran, iran, phone/fax: +982177582721; email: dr.rezamiri1@gmail.com, orcid: https://orcid.org/0000-0002-8568-9948. † corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; email: yousefifard20@gmail.com / yousefifard.m@iums.ac.ir, orcid: https://orcid.org/0000-0001-5181-4985. 1. introduction ischemic heart disease (ihd) is the most common cardiovascular disease and accounts for a vast amount of cardiovascular disease burden. it has been speculated that ihd was the cause of 9.14 million deaths in 2019 (1). knowledge of the outcome of cardiovascular diseases can aid in the timely identification of high-risk patients and their management (2). several scoring tools and markers have been proposed to predict the outcomes of cardiovascular diseases, especially mortality and major adverse cardiovascular events (mace) (3-5). global registry of acute coronary events (grace) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. kabiri et al. 2 and history, ecg, age, risk factors, and troponin (heart) scores are two of the more widely used risk prediction tools in patients with acute coronary syndrome (acs). the grace score was introduced in 2007 and is calculated based on patient’s age, killip class, heart rate, systolic blood pressure, st segment changes, creatinine levels, and elevated cardiac markers to assess the risk of unfavorable outcomes in acs patients (6). the heart risk score was introduced in 2008 for identification of acs patients with a higher risk of adverse outcomes (7). the predictive value of these tools has been investigated in acs patients with promising results (2, 7-11). in a recent systematic review and meta-analysis, ke et al. (12) have indirectly evaluated grace and heart scores in the prediction of mace in acs patients. their results have demonstrated that heart and grace scores could predict mace with a sensitivity of 96% and 78% and specificity of 50% and 56%, respectively, and have concluded that heart is more accurate than grace in the prediction of mace in acs patients. considering that direct comparisons are preferred as a basis for drawing conclusions, the present systematic review and meta-analysis was designed with the aim of directly comparing the value of grace and heart scores in the prediction of acs patient outcomes. 2. methods 2.1. study design and search strategy this systematic review and meta-analysis was designed to evaluate and compare the value of heart and grace tools in the prediction of acs patient outcomes. p (patients): acute coronary syndrome patients, i (index test): grace and heart tools, c (comparison): acs patients without the outcome of the study, o (outcome): major adverse cardiovascular events (mace), acute myocardial infarction (ami), and all-cause mortality were chosen as the definition of pico for the current review. mesh terms of pubmed and emtree terms of embase databases were used to acquire related keywords. chosen keywords were further tailored for the aim of this study by reviewing relevant articles and consultation with experts in the field. the online databases of pubmed, embase, web of science, and scopus were searched until september 10th, 2022, with the specific search strategies devised for each database (supplementary material 1). a manual review of google and google scholar search engines and references of relevant articles was also performed to access any possibly missed studies. 2.2. selection criteria all articles with direct comparisons of grace and heart scores in the adult population were included. the exclusion criteria of this study were review articles, non-english articles, articles with a design of indirect comparison, case series, duplicate records, and articles with no report of required data for this review. 2.3. data extraction the title and abstract of the retrieved records from online databases were screened by two independent reviewers and after the full-text screening, relevant studies were included. reported data were extracted into a checklist designed according to prisma guidelines. the information in the checklist comprised study characteristics (first author, year, country), sample size, age, and male number, the outcome of the study and its definition, event rate of the whole population, and the number of patients who developed outcome in each group, follow-up duration, sensitivity, specificity, true and false positives, and true and false negatives. any conflicts of opinion were resolved by consulting a third reviewer. 2.4. quality assessment and certainty of evidence the quality of the included articles was evaluated using the quality assessment of prognostic accuracy studies (quapas) risk of bias assessment tool (13). according to this tool, studies are evaluated in two sections of risk of bias (consisting of patient selection, index test, reference standard, flow and timing and analysis) and applicability (consisting of patient selection, index test, and reference standard). the certainty of evidence of the included articles was evaluated by the grades of recommendation, assessment, development, and evaluation (grade) guidelines (14). 2.5. statistical analysis stata 17.0 statistical software was used to perform the analysis. reported data were recorded as true and false positives and true and false negatives. “midas” package was used to analyze the data. findings were reported as pooled sensitivity, pooled specificity, area under the curve (auc), positive and negative likelihood ratios, and diagnostic odds ratio. since the results of the articles were reported by different cut-offs, we stratified the analysis based on the reported cutoffs. for this purpose, we categorized grace score cut-offs into two groups of less than and equal to 100 and more than 100, and heart score cut-offs into three groups of less than 4, equal to 4, and more than 4. the publication bias of the included studies was assessed using deeks’ asymmetry funnel plot. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e50 3. results 3.1. study flow and characteristics the systematic search in online databases yielded 1860 nonduplicate records. 59 reports were assessed for eligibility after the title and abstract screening and 25 articles were chosen to be included in this study (2, 15-38). 3 articles were retrieved by manual search, none of which were included (figure 1). the articles comprised data on 21389 suspected acs patients (55.01% male), with a follow-up of at least 30 days (15 articles) with a maximum follow-up time of roughly 8 years. the assessed outcomes were mace (18 articles), ami (6 articles), and all-cause of mortality (3 articles). 19 studies were designed as prospective cohorts, and 6 were retrospective cohorts. the characteristics of the included articles are demonstrated in table 1. 3.2. value of grace and heart risk scores in the prediction of mace studies included 17697 patients (56.1% male) with an event rate of 18.54% (3282 patients) in the evaluation of the value of grace and heart scores in the prediction of mace. the results of the analysis for grace score with cut-offs of less than and equal to 100 and more than 100 showed aucs of 0.71 (95% ci: 0.67, 0.75) and 0.66 (95% ci: 0.62, 0.70), respectively. the sensitivity and specificity of the grace score were 0.96 (95% ci: 0.90, 0.98) and 0.26 (95% ci: 0.16, 0.40) for cut-offs of ≤ 100 and 0.58 (95% ci: 0.53, 0.64) and 0.69 (0.61, 0.77) for cut-offs of >100, respectively. the auc of heart scores less than 4 and equal to 4 was calculated as 0.98 (95% ci: 0.96, 0.99) and 0.72 (95% ci: 0.68, 0.76), respectively. the auc of heart scores more than 4 was 0.84 (95% ci: 0.81, 0.87). the sensitivity and specificity of the heart scores were 0.99 and 0.16 for scores less than 4, 0.93 and 0.47 for equal to 4, and 0.77 and 0.78 for scores greater than 4. based on the presented data, the heart score is best predictive of mace with a cut-off score of 4 (table 2). although it should be mentioned that only 3 articles had data on the prognostic value of heart score with cut-offs of less than 4 (figure 2 and table 2). 3.3. value of grace and heart risk scores in the prediction of ami studies comprised 3591 patients (55.4% male) with an event rate of 13.23% (475 patients) in the assessment of the prognostic values of grace and heart for the prediction of ami. auc of the grace score for the prediction of ami was 0.72 (95% ci: 0.68, 0.76) and the sensitivity and specificity were 0.95 (95% ci: 0.86, 0.98) and 0.29 (95% ci: 0.16, 0.46), respectively (figure 3 and table 2). all studies, except two (21, 23), utilized cut-offs of less than 100. a sensitivity analysis was performed for reports with cut-offs of less than 100 and the results demonstrated an auc of 0.76 (95% ci: 0.72, 0.80), sensitivity of 0.98 (95% ci: 0.93, 0.99) and specificity of 0.18 (95% ci: 0.09, 0.31) for the value of grace score in prediction of ami. the analysis for the value of heart score in the prediction of ami revealed an auc of 0.86 (95% ci: 0.82, 0.88) and a sensitivity and specificity of 0.94 (95% ci: 0.88 and 0.97) and 0.48 (95% ci: 0.32, 0.64), respectively. one article had utilized a cut-off of 3 (16), two articles had not reported the utilized cut-off (21, 24) and the remaining three articles had utilized a cut-off of 4. a sensitivity analysis was performed for the three articles utilizing a cut-off of 4 and the results showed an auc of 0.83 (95% ci: 0.80, 0.86), a sensitivity of 0.94 (95% ci: 0.86, 0.97) and a specificity of 0.51 (95% ci: 0.36, 0.66). 3.4. value of grace and heart risk scores in the prediction of all-cause mortality 1903 patients (79.8% male, 15.24% event rate) were included in the meta-analysis for the value of grace and heart scores in the prediction of all-cause mortality. the results of the analysis showed an auc of 0.75 (95% ci: 0.71, 0.79) for grace and 0.65 (95% ci: 0.61, 0.69) for the heart score. the sensitivity and specificity of grace were 0.82 (95% ci: 0.75, 0.87) and 0.51 (95% ci: 0.42, 0.61), respectively and the sensitivity and specificity of heart score were 0.78 (95% ci: 0.57, 0.90) and 0.56 (95% ci: 0.49, 0.62). two studies utilized a cutoff of more than 100 for the grace score and one study utilized a cut-off of 4 for the heart score, the remaining studies had not reported the cut-off used. due to the scarce number of included studies, sensitivity analysis was not performed (figure 4, table 2). 3.5. publication bias publication bias was only assessed for the outcome of mace, which had more than 10 included studies. no publication bias was observed in the evaluation of the value of grace and heart scores in the prediction of mace (figure 5). 3.6. risk of bias assessment the risk of bias in the domain of patient selection was evaluated to be unclear in eight studies, due to no mention of their sampling method, and high in three studies due to convenient sampling. eight studies had not mentioned the criteria for choosing the risk scores cut-offs and were rated as unclear in risk of bias in the domain of index test and four studies were rated as high in risk of bias in this domain due to choosing their cut-offs based on the calculated aucs. outcome assessment protocol was unclear in seven articles and one article did not provide any outcome definition and was rated as high in risk of bias in the domain of outcome. three studies were rated as unclear in risk of bias in the domain of flow and timing due to possible loss to follow-ups. two studthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. kabiri et al. 4 ies were rated as unclear in the risk of bias in the domain of analysis due to having possible competing events. one study was rated as high in the applicability of outcome due to no outcome definition. the articles were rated as low in the remainder of the domains. overall, the included studies were judged to have a serious risk of bias (table 3). 3.7. certainty of evidence the certainty of the evidence of the included studies was assessed using grade guidelines. the included studies were designed as cohort studies and according to grade guidelines, the base level of evidence was set as high for comparative test accuracy studies. the level of evidence for the outcome of mace was rated down one score due to the serious risk of bias in included articles and thus both scores had a moderate level of evidence for the outcome of mace. the level of evidence in the outcomes of ami and all-cause mortality was rated down two scores for serious risk of bias, and the inability of assessing publication bias due to the limited included studies. the level of evidence for outcomes of ami and all-cause mortality was rated as low for both risk scores (table 4). 4. discussion the current study is the first meta-analysis conducted on the direct comparison of the value of grace and heart scores for the prediction of adverse outcomes in acs patients. we evaluated the predictive value of grace and heart scores in outcomes of mace, ami, and all-cause mortality and our results showed that utilizing grace and heart scores with appropriate cut-offs can predict mace and ami with acceptable sensitivities. the included studies had utilized various cut-off values. our analysis demonstrated that the predictive performance of the grace score for the outcome of mace greatly improves when utilized with cut-off values less than 100 (sensitivity of 0.96 for cut-off values less than 100 and sensitivity of 0.59 for cut-off values more than 100). the predictive value of the heart score was shown to be higher when utilized with cutoffs of less than 4 (sensitivity of 0.99), or equal to 4 (sensitivity of 0.93), and our results suggest that utilization of heart score with a cut-off value of more than 4 (sensitivity of 0.77) cannot be administered as a predictive tool for mace. grace and heart tools were also demonstrated to be good predictors of ami, with sensitivities of 0.95 and 0.94 respectively. further analysis revealed that utilization of the grace score with cut-off values of less than 100, slightly improves its predictive value for ami (sensitivity of 0.98) while subgrouping the analysis of the heart score by the cut-off value of 4, did not reveal any significant changes to its predictive value for ami. in contrast to the acceptable performance of grace and heart scores for the prediction of mace and ami, in our analysis, these scores were not found to be proper predictors of all-cause mortality (sensitivities of 0.82 and 0.78 respectively). although it should be mentioned that our results are limited by the scarce number of included studies investigating the outcome of all-cause mortality. overall, our results have demonstrated low specificity for grace and heart scores in all three outcomes, irrespective of the utilized cutoff. we believe this reiterates the fact that such scores are more suitable to be used as a rule-out tool for identification of acs patients with low risk of developing adverse outcomes, rather than as a rule-in tool to identify patients with higher chances of developing adverse outcomes. previous systematic reviews have evaluated the predictive value of grace and heart scores separately or as an indirect comparison. van den berg et al, suggested that the heart score could be predictive of mace with a sensitivity and specificity of 0.96 and 0.47 respectively (39). whereas ke et al (12) indirectly compared the predictive performance of grace and heart scores and demonstrated a sensitivity and specificity of 0.96 and 0.50 for grace and sensitivity and specificity of 0.78 and 0.56 for heart scores in the prediction of mace. our results for the predictive performance of grace for mace are in line with previous reviews, however, our results demonstrated a better predictive value for the heart score. moreover, we suggest that grace and heart scores can also be used to predict ami in acs patients. although the specified cut-off value chosen for the interpretation of these risk scores is important and can vastly affect their predictive capabilities. considering the fairly similar predictive performances of grace and heart scores in our review, the differences in their design should be kept in mind for better application of these scores. heart score variables are more readily available, and the overall score can be easily calculated. this score relies on the judgment of patient history suspicion which can be challenging due to no exact definition for high, moderate, or slight suspicion, however it has been argued that incorporating clinical gestalt can improve the performance capabilities of the score (26). grace score has been found to be more complex which might require a computer for calculations. there are also fundamental differences in the aims of each score. while heart score aims to identify low-risk chest pain patients for early discharge, grace score was derived for high-risk patients investigating the need for invasive therapy and not for evaluating individuals with undifferentiated chest pain (40-42). it should also be noted that grace and heart scores should be used to enhance the decisionmaking process of the physician and they are never meant to replace clinical decision-making. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e50 5. limitations this systematic review has a few limitations. first, the included studies had differing patient selection criteria. while some studies had included all suspected acs patients, some had only investigated non-st elevation myocardial infarction (mi) acs patients, and few studies had only included st elevation mi acs patients. thus, although our analysis is indicative of all types of acs patients, further studies could evaluate the value of grace and heart scores in specific acs patient settings. the definition of mace in the included articles could affect the predictive value of the grace and heart scores. the articles had varying mace definitions, ranging from a combined endpoint of death or mi to more composite endpoints, which made a subgroup analysis impossible. the included articles had not reported the treatment plan of their patients. considering that different treatment regimens can have an effect on the outcome of patients, future studies could aim to evaluate the predictive value of scoring systems in populations receiving uniform treatments. 6. conclusion the results demonstrated the low specificity of grace and heart scores in predicting the mace, ami and all-cause mortality, irrespective of the utilized cut-off. considering the acceptable sensitivity of two scores in predicting the mace and ami, these scores were more suitable to be used as a rule-out tool for identification of acs patients with low risk of developing adverse outcomes. 7. declarations 7.1. acknowledgments none. 7.2. conflict of interest the authors declare that they have no competing interests. 7.3. funding and support this study was funded by shahid beheshti university of medical sciences. 7.4. authors’ contribution study design: my, rm data gathering: ak, pg, saf analysis: my, ka interpretation of results: all authors drafting and revising: all authors all authors read and approved final version. 7.5. using artificial intelligence chatbots none. 7.6. availability of data and materials the gathered data and checklist can be provided to qualified researchers with the intent of replicating the procedure and results. references 1. roth ga, mensah ga, johnson co, addolorato g, ammirati e, baddour lm, et al. global burden of cardiovascular diseases and risk factors, 1990–2019: update from the gbd 2019 study. journal of the american college of cardiology. 2020;76(25):2982-3021. 2. huang z, wang k, yang d, gu q, wei q, yang z, et al. the predictive value of the heart and grace scores for major adverse cardiac events in patients with acute chest pain. intern emerg med. 2021;16(1):193-200. 3. ramezani f, ahmadi s, faridaalee g, baratloo a, yousefifard m. value of manchester acute coronary syndromes decision rule in the detection of acute 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2021;136:14656. 15. al-zaiti ss, faramand z, alrawashdeh mo, sereika sm, martin-gill c, callaway c. comparison of clinical risk scores for triaging high-risk chest pain patients at the emergency department. am j emerg med. 2019;37(3):461-7. 16. carlton ew, khattab a, greaves k. identifying patients suitable for discharge after a single-presentation highsensitivity troponin result: a comparison of five established risk scores and two high-sensitivity assays. ann emerg med. 2015;66(6):635-45 e1. 17. chae mk, kim ek, jung ky, shin tg, sim ms, jo ij, et al. triple rule-out computed tomography for risk stratification of patients with acute chest pain. j cardiovasc comput tomogr. 2016;10(4):291-300. 18. chen xh, jiang hl, li ym, chan cpy, mo jr, tian cw, et al. prognostic values of 4 risk scores in chinese patients with chest pain: prospective 2-centre cohort study. medicine (baltimore). 2016;95(52):e4778. 19. chew pg, frost f, mullen l, fisher m, zadeh h, grainger r, et al. a direct 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acute myocardial infarction in elderly patients presenting to the emergency department with acute chest pain. bratisl lek listy. 2022;123(4):28290. 24. jukneviciene r, juknevicius v, jasiunas e, rasciute b, barysiene j, mataciunas m, et al. chest pain in the emergency department: from score to corea prospective clinical study. medicine (baltimore). 2022;101(29):e29579. 25. liu n, sakamoto jt, cao j, koh zx, ho afw, lin z, et al. ensemble-based risk scoring with extreme learning machine for prediction of adverse cardiac events. cognitive computation. 2017;9(4):545-54. 26. ng m, tan hjg, gao f, tan jwc, lim sh, ong meh, et al. comparative prospective study of the performance of chest pain scores and clinical assessment in an emergency department cohort in singapore. j am coll emerg physicians open. 2020;1(5):723-9. 27. poldervaart jm, langedijk m, backus be, dekker imc, six aj, doevendans pa, et al. comparison of the grace, heart and timi score to predict major adverse cardiac events in chest pain patients at the emergency department. int j cardiol. 2017;227:656-61. 28. reaney pdw, elliott hi, noman a, cooper jg. risk stratifying chest pain patients in the emergency department using heart, grace and timi scores, with a single contemporary troponin result, to predict major adverse cardiac events. emerg med j. 2018;35(7):420-7. 29. ruangsomboon o, thirawattanasoot n, chakorn t, limsuwat c, monsomboon a, praphruetkit n, et al. the utility of the 1-hour high-sensitivity cardiac troponin t algorithm compared with and combined with five early ruleout scores in high-acuity chest pain emergency patients. int j cardiol. 2021;322:23-8. 30. sakamoto jt, liu n, koh zx, fung nx, heldeweg ml, ng jc, et al. comparing heart, timi, and grace scores for prediction of 30-day major adverse cardiac events in high acuity chest pain patients in the emergency department. int j cardiol. 2016;221:759-64. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e50 31. shin ys, ahn s, kim yj, ryoo sm, sohn ch, kim wy. risk stratification of patients with chest pain or anginal equivalents in the emergency department. intern emerg med. 2020;15(2):319-26. 32. singer aj, than mp, smith s, mccullough p, barrett tw, birkhahn r, et al. missed myocardial infarctions in ed patients prospectively categorized as low risk by established risk scores. am j emerg med. 2017;35(5):704-9. 33. steiro ot, tjora hl, langorgen j, bjorneklett r, nygard ok, skadberg o, et al. clinical risk scores identify more patients at risk for cardiovascular events within 30 days as compared to standard acs risk criteria: the westcor study. eur heart j acute cardiovasc care. 2021;10(3):287301. 34. tekin e, ozlu i, onur can n, yilmaz s. comparison of the integrated pulmonary index with cardiac risk scores in acute coronary syndromes. annals of clinical and analytical medicine. 2021;12(03). 35. torralba f, navarro a, la hoz jc, ortiz c, botero a, alarcon f, et al. heart, timi, and grace scores for prediction of 30-day major adverse cardiovascular events in the era of high-sensitivity troponin. arq bras cardiol. 2020;114(5):795-802. 36. wong cp, lui ct, sung jg, lam h, fung ht, yam pw. prognosticating clinical prediction scores without clinical gestalt for patients with chest pain in the emergency department. j emerg med. 2018;54(2):176-85. 37. yang b, bai l, zhang y, cheng y, zhao c, huang b, et al. the value of different short-term risk scoring models in predicting long-term death of acute myocardial infarction. j clin med. 2022;11(17). 38. zheng w, wang g, ma j, wu s, zhang h, zheng j, et al. evaluation and comparison of six grace models for the stratification of undifferentiated chest pain in the emergency department. bmc cardiovasc disord. 2020;20(1):199. 39. van den berg p, body r. the heart score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis. eur heart j acute cardiovasc care. 2018;7(2):111-9. 40. six aj, backus be, kelder jc. chest pain in the emergency room: value of the heart dvotr. netherlands heart journal. 2008;16(6):191-6. 41. backus be, six aj, kelder jh, gibler wb, moll fl, doevendans pa. risk scores for patients with chest pain: evaluation in the emergency department. current cardiology reviews. 2011;7(1):2-8. 42. brady w, de souza k. the heart score: a guide to its application in the emergency department. turk j emerg med. 2018;18(2):47-51. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. kabiri et al. 8 table 1: characteristics of included studies study country design follow up (day) sample size male (n) age* (year) outcome: number grace cut-off heart cut-off al-zaiti 2018 us rcs 30 750 433 59±17 mace: 33 109 4 carlton 2015 uk pcs 30 959 564 58±13.3 ami: 79 60, 80 3, 4 chae 2016 south korea pcs 30 1024 594 58 (50-69) mace: 126 108 4 chen 2016 china pcs 30, 180 833 461 65.1±14.5 mace: 121 109, 114 4, 5 chew 2018 uk pcs 42, 365 1642 858 59.35±18.54 mace: 279 ami: 180 76 4 dinesh 2022 india pcs 42 199 138 51.61±16.47 mace: 76 119 7 dupuy 2021 france pcs 30 160 94 73 to 80 ami: 37 death: 13 nr nr han 2017 taiwan rcs 180 249 203 61.7±14.91 death: 41 121 nr hrecko 2022 finland rcs 30 250 126 78.5±8.2 ami: 48 109 4 huang 2021 china pcs 30 509 293 59.77±14.9 mace: 92 106 4 jukneviciene 2022 lithuania pcs 180 146 95 63±13.4 ami: 51 nr nr liu 2017 singapore pcs nr 797 542 nr mace: 146 108 5 mingwei ng 2020 singapore pcs 30 1195 817 nr mace: 135 109 4 poldervaart 2017 netherlands pcs 42 1748 937 62±14 mace: 326 73 4 reaney 2017 uk pcs 30 1000 574 62.4±15.6 mace: 189 56, 119 4, 7 ruangsomboon 2020 thailand pcs 30 350 185 66.3±15.1 mace: 59 56, 66 3, 4 sakamoto 2016 singapore pcs 30 604 417 60.8±13.2 mace: 215 76, 111 4, 5 shin 2020 korea rcs 30, 90 1247 758 62±12.7 mace: 211 109 4 singer 2017 us pcs 30 434 251 56.64±11.15 ami: 80 51 4 steiro 2021 norway rcs 30, 180 932 562 63±16.33 mace: 191 90, 109 4 tekin 2021 turkey pcs 30 381 195 nr mace: 105 115 6 torralba 2020 colombia pcs 30 519 291 64.31±12.11 mace: 224 109 4 wong 2017 hong kong pcs 30 1081 565 48±27 mace: 164 50,75,100 1, 2 yang 2022 china rcs 2956 1494 1221 63 (53-72) death: 236 126 4 zheng 2020 china pcs 30 2886 1447 64±13.5 mace: 590 81 4 data are presented as mean ± standard deviation or median (interquartile range). ami: acute myocardial infarction, mace: major adverse cardiovascular event, nr: not reported, pcs: prospective cohort study, rcs: retrospective cohort study table 2: performance of grace and mace scores in prediction of outcomes system cut-off sensitivity specificity auc plr nlr or major adverse cardiovascular event (mace) grace ≤100 0.96 (0.90, 0.98) 0.26 (0.16, 0.40) 0.71 (0.67, 0.75) 1.3 (1.1, 1.5) 0.17 (0.10, 0.27) 8 (5, 12) >100 0.58 (0.53, 0.64) 0.69 (0.61, 0.77) 0.66 (0.62, 0.70) 1.9 (1.5, 2.3) 0.60 (0.54, 0.67) 3 (2, 4) heart <4 0.99 (0.97, 0.99) 0.16 (0.08, 0.29) 0.98 (0.96, 0.99) 1.2 (1.0, 1.3) 0.09 (0.03, 0.25) 13 (4, 36) 4 0.93 (0.88, 0.96) 0.47 (0.40, 0.54) 0.72 (0.68, 0.76) 1.8 (1.6, 2.0) 0.14 (0.08, 0.23) 13 (8, 21) >4 0.77 (0.63, 0.87) 0.78 (0.59, 0.90) 0.84 (0.81, 0.87) 3.6 (1.8, 7.2) 0.29 (0.17, 0.49) 12 (5, 34) acute myocardial infarction (ami) grace na 0.95 (0.86, 0.98) 0.29 (0.16, 0.46) 0.72 (0.68, 0.76) 1.3 (1.1, 1.6) 0.18 (0.10, 0.33) 7 (4, 12) heart na 0.94 (0.88, 0.97) 0.48 (0.32, 0.64) 0.86 (0.82, 0.88) 1.8 (1.4, 2.4) 0.12 (0.08, 0.21) 14 (9, 23) all-cause mortality grace na 0.82 (0.75, 0.87) 0.51 (0.42, 0.61) 0.75 (0.71, 0.79) 1.7 (1.5, 1.9) 0.36 (0.29, 0.44) 5 (4, 6) heart na 0.78 (0.57, 0.90) 0.56 (0.49, 0.62) 0.65 (0.61, 0.69) 1.8 (1.3, 2.4) 0.39 (0.18, 0.89) 4 (1, 13) all measures are presented with 95% confidence interval. plr: positive likelihood ratio; nlr: negative likelihood ratio; or: diagnostic odds ratio; auc: area under the curve; 95% ci: confidence interval; na: not applicable. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e50 figure 1: prisma flow diagram. table 3: risk of bias assessment study, year risk of bias applicability overall patient selection index test outcome flow and timing analysis patient selection index test outcome flow and timing al-zaiti, 2018 low low low unclear unclear low low low low some concern carlton, 2015 low low low low unclear low low low low some concern chae, 2016 unclear low low low low low low low low some concern chen, 2016 low low unclear low low low low low low some concern chew, 2018 low unclear unclear low low low low low low some concern dinesh, 2022 low unclear unclear low low low low low low some concern dupuy, 2021 unclear unclear low low low low low low low some concern han, 2017 low high low low low low low low low some concern hrecko, 2022 low low unclear unclear unclear low low low low some concern huang, 2021 unclear unclear low low low low low low low some concern jukneviciene, 2022 low unclear low unclear unclear low low low low some concern liu, 2017 high high low low low low low low low some concern mingwei, 2020 high low low low low low low low low some concern poldervaar, 2016 low low low low low low low low low low reaney, 2017 high low unclear low low low low low low some concern ruansomboon, 2020 low unclear low low low low low low low some concern sakamoto, 2016 unclear low unclear low low low low low low some concern shin, 2020 low low unclear low low low low low low some concern singer, 2017 unclear unclear low low unclear low low low low some concern steiro, 2021 unclear low low low low low low low low some concern tekin, 2021 unclear high high low low low low high low some concern torralba, 2020 unclear low low low low low low low low some concern wong, 2017 low unclear low low low low low low low some concern yang, 2022 low high low low low low low low low some concern zheng, 2020 low low low low low low low low low some concern this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. kabiri et al. 10 figure 2: performance of grace score with cut-off values of ≤ 100 (a) and > 100 (b) and heart score with cut-off values < 4 (c), equal to 4 (d) and greater than 4 (e) in the prediction of major adverse cardiovascular events. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e50 figure 3: performance of grace score (a) and heart score (b) in the prediction of acute myocardial infarction. figure 4: performance of grace score (a) and heart score (b) in the prediction of all-cause mortality. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. kabiri et al. 12 figure 5: publication bias of the included articles for the value of grace (a) and heart (b) in the prediction of major adverse cardiovascular events. table 4: certainty of evidence outcome study/ population study design factors that may decrease certainty of evidence certainty of evidence risk of bias indirectness inconsistency imprecision publication bias major adverse cardiovascular event grace cut-offs ≤ 100 8 studies n = 10243 cohort studies serious not serious not serious not serious not serious ○ ⊕⊕⊕⊕ moderate cut-offs > 100 13 studies n = 10793 cut-off < 4 2 studies n = 1431 heart cut-off = 4 14 studies n = 15239 cohort studies serious not serious not serious not serious not serious ○ ⊕⊕⊕⊕ moderate cut-offs > 4 6 studies n = 3814 acute myocardial infarction grace cut-offs: na 6 studies n = 3591 cohort studies serious not serious not serious not serious not applicable ○ ⊕⊕⊕ ○ low heart cut-off: na 6 studies n = 3591 cohort studies serious not serious not serious not serious not applicable ○ ⊕⊕⊕ ○ low all-cause mortality grace cut-off: na 3 studies n = 1903 cohort studies serious not serious not serious not serious not applicable ○ ⊕⊕⊕ ○ low heart cut-off: na 3 studies n = 1903 cohort studies serious not serious not serious not serious not applicable ○ ⊕⊕⊕ ○ low this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e50 supplementary table 1: search strategy pubmed: ((global registry acute coronary events[tiab] or grace[tiab]) and (heart[tiab])) and (scor*[tiab] or scal*[tiab] or tool*[tiab] or mode*[tiab] or pathway[tiab]or assessment*[tiab]) embase: (’global registry of acute coronary events’/exp or ’global registry of acute coronary events’:ab,ti or ’grace’:ab,ti or ’global registry for acute coronary events’:ab,ti) and (’scor*’:ab,ti or ’scal*’:ab,ti or ’tool*’:ab,ti or ’mode*’:ab,ti or ’pathway’:ab,ti or ’assessment*’:ab,ti) and (’history electrocardiogram age risk factors and troponin score’/exp or ’history electrocardiogram age risk factors and troponin score’ or ’heart’:ab,ti) scopus: title-abs-key(“global registry of acute coronary events” or “grace” or “global registry for acute coronary events”) and title-abskey( “scor*” or “scal*” or “tool*” or “mode*” or “pathway” or “assessment*”) and title-abs-key(“history electrocardiogram age risk factors and troponin score” or “heart”) web of science (((ts=(“global registry of acute coronary events” or “grace” or “global registry for acute coronary events”))) and ts=(“scor*” or “scal*” or “tool*” or “mode*” or “pathway” or “assessment*”)) and ts=(“history electrocardiogram age risk factors and troponin score” or “heart”) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency 2016; 4 (3): 145-150 or i g i n a l re s e a rc h epidemiology and death-related factors of oncology patients in emergency department bahram mofid1, kambiz novin1, elham sadat roointan1, mohammad mehdi forouzanfar2∗ 1. department of radiation oncology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2015; accepted: september 2015 abstract: introduction: accurate diagnosis and proper treatment of oncology patients presented to emergency department (ed) can dramatically enhance their quality of life and decrease their mortality rate. therefore, the present study aimed to evaluate these patients from an epidemiologic point of view as well as identifying death-related factors. methods: in this retrospective cross-sectional study, all the oncology patients presented to ed during one year were evaluated using census sampling. a checklist that consisted of clinical and demographic data as well as patients outcome was filled for each patient. using spss 21, multivariate stepwise logistic regression analysis was done to identify independent death-related factors. results: 568 patients with the mean age of 53.64 ± 18.99 years were studied (56.5% male). the most common locations of tumor were brain (32.7%) and gastrointestinal tract (27.1%). pain (32.5%) was the most frequent chief complaint on ed arrival. the overall mortality rate of studied patients was 154 (27.1%), 25 (16.2%) of them in ed. among the evaluated factors, marital status, visiting on a weekday, arrival to ed via ambulance, type of cancer, stage of cancer, presence of metastasis, being under treatment with chemo-radiotherapy, chief complaint on arrival, tumor location, and admission to intensive care unit (icu) correlated significantly with in-hospital mortality. conclusion: the most common type of cancer in the studied patients was solid, located in the brain or gastrointestinal tract, in stage iii and iv, metastatic, and under chemo-radiotherapy. independent death-related factors included icu admission, presentation with loss of consciousness or bleeding, arrival via ambulance, cancer stage > ii, neuroendocrine and genitourinary location of cancer, and being under chemo-radiotherapy. keywords: oncology service, hospital; hospital mortality; epidemiology; emergency medicine © copyright (2015) shahid beheshti university of medical sciences cite this article as: mofid b, novin k, roointan es, forouzanfar mm. epidemiology and death-related factors of oncology patients in emergency department . emergency. 2016; 4(3):145-150. 1. introduction c ancer is the second cause of death behind cardiovascular diseases, worldwide (1). based on the report of international agency for research on cancer (iarc) in globocan 2012, the most common location and highest mortality rate belongs to pulmonary cancer in men and breast cancer in women. based on the same report, risk of developing cancer before the age of 75 years old is 18.5% for both sexes, while the risk of mortality due to cancer is 10.5% in the same age range. iarc reported the most common cancers in both sexes to be pulmonary, breast, colorec∗corresponding author: mohammad mehdi forouzanfar; emergency department, shohadaye tajrish hospital, tajrish square, tehran, iran; tel/fax: 00989123708649; email: drfrouzanfar@yahoo.com. tal, prostate, and gastric cancers, in the mentioned order (2). developing new treatment strategies for cancer patients has led to an increase in their life-span and frequency of emergency department (ed) visits (3). ed is one of the most important places for rapidly addressing the complaints of these patients. most of these patients visit ed at least once over the course of their disease (4). recently, many studies have been done to evaluate the different aspects of oncology patients in ed (1, 3–11). accurate diagnosis and proper treatment of these patients in ed can dramatically enhance their quality of life and decrease their mortality rate (8). having enough epidemiologic data and a proper plan for managing these patients in ed are necessary for reaching this purpose. therefore, the present study was designed, aiming to evaluate oncology patients presented to ed from an epidemiologic point of view as well as identifying death-related factors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com drfrouzanfar@yahoo.com mofid et al. 146 2. methods 2.1. study design and setting in the present retrospective cross-sectional study, all the oncology patients presented to the ed of shohadaye tajrish hospital, tehran, iran, during one year from april 2014 to march 2015, were evaluated using census sampling. no age or sex limitations were implemented in this study. if the patient died on their way to the hospital, they were excluded. the present study was approved by the ethics committee of shahid beheshti university of medical sciences. all the researchers adhered to the principles of helsinki declaration during the course of the study. 2.2. data gathering a checklist that consisted of demographic data (age, sex, marital status, living area, employment), type of arrival to ed, day and time of ed visit, history of visits, patient complaints on arrival, cancer characteristics (type, location, stage, presence and location of metastasis), special treatment characteristics (chemotherapy, radiotherapy, chemo-radiotherapy), and ed disposition and final outcome (discharge from ed, hospitalization in oncology ward or intensive care unit (icu), mortality) was filled for each patient. the data were extracted from the patients clinical profiles. by searching in the medical records unit, all dead, hospitalized, and discharged oncology patients in ed were evaluated. 2.3. statistical analysis all statistical analyses were done using spss version 21. qualitative variables were reported as frequency and percentage, and quantitative ones as mean and standard deviation. chi square and fisher’s tests were used to identify variables that had significant correlation with mortality. in addition, multivariate stepwise logistic regression analysis was done on significant factors to identify independent deathrelated factors. type i error (a) was considered 0.05. 3. results 568 patients with the mean age of 53.64 ± 18.99 years (2– 94) had visited during the study period (56.5% male). 500 (88%) patients experienced their first visit and 367 (64.7%) were presented in the night shift. 372 (65.5%) patients arrived at the ed in a private car. the most common location of tumor were brain (32.7%) and gastrointestinal (27.1%). 247 (43.5%) of the tumors were metastatic. tables 1 and 2 depict the baseline characteristics of the patients based on their survival. in addition, table 3 summarizes the final outcome of the patients. the overall mortality rate of studied patients was 154 (27.1%), 25 (16.2%) of them in ed. among the evaluated factors marital status (p = 0.009), visiting on a weekday (p = 0.044), arrival to ed via ambulance (p < 0.001), type of cancer (p = 0.048), stage of cancer (p < 0.001), presence of metastasis (p < 0.001), being under treatment with chemoradiotherapy (p < 0.001), chief complaint on arrival (p < 0.001), tumor location (p = 0.04), and hospitalization in icu (p < 0.001) correlated with inhospital mortality (tables 1 and 2). table 4 shows the results of stepwise logistic regression analysis. 4. discussion based on the results, the most common type of cancer in the studied patients was solid (94.5%), located in the brain (32.7%) or gastrointestinal tract (27.1%), in stage iv (50.4%), metastatic (43.5%), and under treatment with chemoradiotherapy (49.9%). finally, 154 (27.1%) patients had died (16.2% in ed) and more than 90% of those who had visited ed had needed hospitalization in the oncology ward. the independent death-related factors were hospitalization in icu, ed presentation with loss of consciousness or bleeding, arrival via ambulance, cancer stage > ii, neuroendocrine and genitourinary location of cancer, and being under chemoradiotherapy. currently, despite the advances in cancer treatment, it is still a major health problem and cancer patients commonly face medical emergencies and unexpected life-threatening diseases (3, 12). these patients are most commonly admitted to ed for decreasing the cancer-related symptoms, controlling treatment side effects, oncology emergencies, simultaneous diseases, or palliative care (7, 13, 14). mean age of oncology patients visiting the ed has been estimated to be between 60 to 68 years in various studies (1, 11, 15, 16). in the present study, mean age of patients was 53.64±18.99 years (2–94) and most were in the 50–75 age range. regarding sex distribution, the findings of the present study were in line with previous studies (4, 7, 8). epigastric pain, nausea and vomiting, and shortness of breath are among the frequent reported causes of ed visit in previous studies (7, 8, 11). while, in the present study, the most common chief complaint of the patients on ed admission was pain, which is in line with the findings of kraft rovere et al., mayer et al., and barbera et al. (7, 9, 10, 15). in the present study, most cancers were solid (73.7%), which is similar to the bozdemir et al. study result (88%) (11). the most common location of tumor in our study was brain (32.7%), followed by gastrointestinal tract (27.1%). the most frequent reported tumor locations are lung, gastrointestinal, and respiratory tracts in similar studies (1, 4, 7, 9–11). out of the 568 cancer patients presented to the ed, 90.3% were subsequently hospitalized in the oncology department, 5.3% were discharged, and 4.4% died. death rate in the ed was estimated to be 8-9% in various studies (4, 8). lower ed morthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 147 emergency 2016; 4 (3): 145-150 table 1: comparison of baseline characteristics between survived and dead patients variable total survival death p value sex female 247 (43.5) 178 (72.1) 69 (27.9) 0.385 male 321 (56.5) 236 (73.5) 85 (26.5) age (year) 1–24.9 39 (6.8) 33 (84.9) 6 (15.4) 0.003 25–49.9 173 (30.4) 136 (78.6) 37 (21.4) 50–74.9 271 (47.7) 195 (72) 76 (28) 75–99.9 85 (14.9) 50 (58.8) 35 (41.2) marital status single 63 (11.1) 54 (85.7) 9 (14.3) 0.009 married 505 (88.9) 360 (71.3) 145 (28.7) employment employed 316 (55.6) 229 (72.5) 87 (27.5) 0.961 unemployed 240 (42.3) 176 (73.3) 64 (26.7) time of arrival day 200 (35.2) 140 (70) 60 (30) 0.236 night 367 (64.7) 274 (74.7) 93 (23.3) day of arrival weekend 88 (15.5) 57 (64.8) 31 (35.2) 0.044 weekday 480 (84.5) 357 (74.4) 123 (25.6) living area urban 550 (96.8) 399 (72.5) 151 (27.5) 0.235 rural 18 (3.2) 15 (83.3) 3 (16.7) transportation to ed ambulance 182 (32) 70 (38.5) 112 (61.5) < 0.001 private car 372 (65.5) 334 (89.8) 38 (10.2) number of ed visits 1 500 (88) 360 (72) 140 (28) 0.3332 64 (11.3) 50 (78) 14 (21.9) 3 3 (5) 3 (100) 0 (0) type of cancer solid 537 (94.5) 396 (73.7) 141 (26.3) 0.048 hematologic 31 (5.5) 18 (58.1) 13 (41.9) stage of cancer i 29 (5.1) 27 (93.1) 2 (6.9) < 0.001ii 100 (17.6) 96 (96) 4 (4) iii 128 (22.5) 102 (79.7) 26 (20.3) iv 286 (50.4) 167 (58.4) 119 (41.6) multiple cancers yes 32 (5.6) 23 (71.9) 9 (28.1) 0.517 no 536 (94.4) 391 (72.9) 145 (27.1) metastasis positive 247 (43.5) 147 (59.5) 100 (40.5) < 0.001 negative 320 (56.3) 266 (83.1) 54 (16.9) treatment chemotherapy 140 (24.6) 95 (67.9) 45 (32.1) < 0.001radiotherapy 32 (5.6) 22 (68.8) 10 (31.3) chemo-radiotherapy 59 (57.3) 178 (72.1) 44 (42.7) none 293 (51.6) 238 (81.2) 55 (18.8) tality rate (4.4%) in the present study might be due to rapid disposition of the patients to other wards and their higher rate of hospitalization. in other words, ed mortality rate has decreased in return to a rise in other wards mortality rate. based on the findings of the present study, independent death-related factors in this study included hospitalization in icu, visiting due to loss of consciousness or bleeding, arrival via ambulance, higher stage of cancer, tumor type, and being this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com mofid et al. 148 table 2: comparison of baseline characteristics between survived and dead patients (continued) variable total survival death p value icu admission yes 20 (3.9) 6 (30) 14 (70) < 0.001 no 482 (24.1) 371 (77) 111 (23) ed chief complaints fever 12 (2.1) 11 (91.7) 1 (8.3) < 0.001 loss of consciousness 132 (23.2) 65 (49.2) 67 (50.8) respiratory distress 51 (8.9) 30 (58.8) 21 (41.2) gastrointestinal disorder 42 (7.3) 35 (83.3) 7 (16.7) pain 185 (32.5) 149 (80.5) 36 (19.5) focal neurologic deficit 91 (16.0) 81 (89) 10 (11) bleeding 16 (2.8) 12 (75) 4 (25) ulcer 13 (2.2) 8 (61.5) 5 (38.5) mass 22 (3.8) 21 (95.5) 1 (4.5) extremity edema 4 (0.7) 2 (50) 2 (50) tumor location brain 186 (32.7) 156 (83.9) 30 (16.1) < 0.004 breast 56 (9.9) 40 (71.4) 16 (28.6) prostate 31(5.5) 18 (58.1) 13 (41.9) gastrointestinal 154 (27.1) 106 (68.8) 48 (31.2) respiratory 24 (4.2) 15 (62.5) 9 (37.5) genitourinary 79 (13.9) 51 (64.6) 28 (35.4) lymphoma 4 (0.7) 4 (100) 0 (0) skin 4 (0.7) 3 (75) 1 (25) neuroendocrine 20 (3.5) 15 (75) 5 (25) liposarcoma 1 (0.2) 0 (0) 1 (100) bone 3 (0.5) 3 (100) 0 (0) neck 2 (0.4) 2 (100) 0 (0) heart 1 (0.2) 0 (0) 1 (100) cholangiocarcinoma 2 (0.4) 1 (50) 1 (50) muscle 1 (0.2) 0 (0) 1 (100) location of metastasis brain 21 (9) 13 (61.9) 8 (38.1) < 0.332 bone 36 (15.5) 28 (77.8) 8 (22.2) lung 36 (15.5) 22 (61.1) 14 (8.1) multiple 57 (24.5) 24 (42.1) 33 (57.9) pleura 7 (3.0) 5 (71.4) 2 (28.6) uterus 3 (1.2) 3 (100) 0 (0) bladder 4 (1.7) 2 (50) 2 (50) liver 47 (20.2) 28 (59.6) 19 (40.4) pancreas 3 (1.2) 2 (66.7) 1 (33.3) kidney 4 (1.7) 2 (50) 2 (50) rectum 1 (0.4) 0 (0) 1 (100) peritoneum 3 (1.2) 2 (66.7) 1 (33.3) colon 3 (1.2) 2 (66.7) 1 (33.3) pelvic organs 1 (0.4) 1 (100) 0 (0) stomach 1 (0.4) 1 (50) 1 (50) abdominal 2 (0.8) 1 (50) 1 (50) neck 2 (0.8) 2 (100) 0 (0) ed: emergency department; icu: intensive care unit. under chemo-radiotherapy. as can be seen, most of these factors are related to severity of disease on admission. for instance, in the studied ed, most of the patients who had arrived via an ambulance were in a worse condition compared to those who had arrived by themselves or accompanied by relatives, and therefore died more. on the other hand, patients in a more severe condition were more commonly admitted to icu and naturally had a higher death rate. it seems that patients who visited the studied ed were similar to the participants of other studies from an epidemiologic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 149 emergency 2016; 4 (3): 145-150 table 3: outcome of the studied patients outcome number (%) emergency ward discharge 30 (5.3) death 25 (4.4) hospitalization 513 (90.3) oncology ward discharge 384 (74.9) death 129 (25.1) table 4: the results of multivariate stepwise logistic regression analysis variables odds ratio (95% ci) p value icu admission yes 4.90 (1.36160.61) 0.027 chief complaint loss of consciousness 3.01 (1.665.44) < 0.001 bleeding 5.20 (0.9827.60) 0.052 transportation to ed private car 0.09 (0.50.17) < 0.001 stage of cancer ii 0.17 (0.050.53) 0.002 treatment chemo-radiotherapy 2.16 (1.154.04) 0.016 tumor location neuroendocrine 4.46 (1.0518.94) 0.043 genitourinary 3.85 (1.788.29) 0.001 ci: confidence interval; icu: intensive care unit. point of view and the differences present are a result of the natural differences in hospitals regarding patient admission policies and available specialties. multi-centric studies can be helpful in this respect. we should be cautious about using the results of this study since the study design has some limitations for this kind of conclusion. 5. conclusion based on the results, the most common type of cancer in the studied patients was solid, located in the brain or gastrointestinal tract, in stage iii and iv, metastatic, and under chemo-radiotherapy. the factors correlating with hospital mortality included hospitalization in icu, ed presentation with loss of consciousness or bleeding, arrival via ambulance, cancer stage > ii, neuroendocrine and genitourinary location of cancer, and being under chemo-radiotherapy. 6. appendix acknowledgements the authors appreciate the insightful cooperation of emergency department staff. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. funding none. conflict of interest none. references 1. swenson kk, rose ma, ritz l, murray cl, adlis sa. recognition and evaluation of oncology-related symptoms in the emergency department. annals of emergency medicine. 1995;26(1):12–7. 2. ferlay j, soerjomataram i, dikshit r, et al. cancer incidence and mortality worldwide: sources, 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satisfaction. clinical oncology. 2009;21(3):226–33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 141 emergency (2015); 3 (4): 141-145 original research an epidemiologic study of traumatic brain injuries in emergency department vahid monsef kasmaei, payman asadi*, behzad zohrevandi, mohammad taghi raouf road trauma research center, guilan university of medical sciences, rasht, iran. *corresponding author: payman asadi; road trauma research center, guilan university of medical sciences, rasht, iran. tel: +989113344071. fax: +981313238373; email: payman.asadi@yahoo.com received: december 2014; accepted: january 2015 abstract introduction: traumatic brain injuries (tbi) are one of the most important causes of death in patients under the age of 25 years and is responsible for one third of total deaths caused by trauma. therefore, knowing its epidemiologic pattern in different populations seems vital. therefore, this study aims to examine the epidemiologic pattern of tbi in emergency department. methods: in this cross-sectional study, the profiles of 1000 patients affected by tbi were selected using simple random sampling. the examined variables in this study included demographic, season, mechanism of injury, accompanying injuries, level of consciousness, hospitalization duration, computed tomography (ct) scan results, needing surgery, admission to intensive care unit, and outcome of the patient. in the end, independent risk factors for the death of patients were determined. results: 1000 patients suffering from were studied (81.8% male; mean age 38.5±21.7 years). the frequency of their referral to hospital in spring (31.4%) was more (p<0.01). 45.9% of the patients had a level of consciousness less than 9 based on the glasgow coma scale (gcs). subdural (45.9%) and epidural bleeding (23.7%) were the most common findings in ct scans in this study (p<0.001). finally, 233 (23.3%) of the patients were dead. over 60 years of age, falling and motorcycle accidents, intracranial hemorrhage accompanied by brain contusion, subdural bleeding, a gcs of less than 9, and the need to be admitted to intensive care unit were independent risk factors of death in tbi. conclusion: age over 60 years, falling and motorcycle accidents, intracranial hemorrhage accompanied by brain contusion, subdural bleeding, a gcs of less than 9, and need to be admitted to intensive care unit were independent risk factors for the death in tbi patients. key words: brain injuries; head injuries; epidemiology; mortality; risk factors cite this article as: monsef kasmaie v, asadi p, zohrevandi b, raouf mt. an epidemiologic study of traumatic brain injuries in emergency department. emergency. 2015;3(4):141-5. introduction: rauma, as 1 of the 5 major causes of death and disability in the world, leads to about 5 million deaths per year or 16 thousand deaths daily (1). in iran, accidents are the leading cause of death in the youth and the major reason for years of potential life lost (2). traumatic brain injuries (tbi) are among the worst consequences of these accidents and are the major causes of death in patients under the age of 25 years (3). it is also the leading cause of trauma related coma and disabilities (4). in developed countries the rate of deaths induced by head injury has been about 21% (in the first month) and this rate goes up to 50% in developing countries (5, 6). tbi occurrence is increasing as motor vehicles are being more widely used in the developing countries (7). in its last report, the world health organization (who) has stated the need for more research on the epidemiologic pattern of accidents in low and middle-income countries to determine the dimensions of the problem and identify susceptible people. despite the valuable efforts made in the past few years to determine the epidemiology pattern of trauma and their outcomes in iran, available data still seems insufficient (8). as tbi are one of the most common and dangerous outcomes of accidents, the present study aims to determine the epidemiologic pattern of tbi in emergency department. the results from this study will be of help to identify the pattern of accident type, age, and sex distribution and the prevalence of other clinical and practical factors in traumatic brain injuries. methods: study design and setting this cross-sectional, retrospective study was aimed to determine the epidemiologic pattern of tbi in the emergency patients admitted to poorsina hospital, rasht, iran t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com monsef kasmaei et al 142 from 2012 to 2013. poorsina hospital is one of the most important trauma center of northern iran, admitting about 18 thousand patients annually (9). this study has been approved by the ethics committee of gilan university of medical sciences and the researchers have adhered to the principles of the helsinki declaration. participants the sample population consisted of all of the patients admitted to emergency department of poorsina hospital, who were diagnosed as tbi. simple random sampling was used. in the beginning, all of the tbi patients’ profiles were sorted alphabetically. then, using a web based random number table, 1000 profiles were chosen randomly and were studied. exclusion criteria included incomplete profile, no final decision recorded, no recorded ct scan result and making a final decision using tests other than ct scan. to reach the minimum number of samples required considering the 21% death rate in tbi (5), 95% confidence interval (α=0.05), 90% statistical power (β=0.1) and 1% accuracy (d=0.01), 865 samples were sufficient. studied variables the studied variables in this study included demographic (age, sex, marital status, level of education, occupation, place of residence), season, mechanism of trauma, presence of accompanying injuries, level of consciousness based on the glasgow coma scale (gcs), hospitalization duration, ct scan results, needing surgery, needing admission to intensive care unit and the final outcome of patient. patient outcome was divided into 3 groups: discharged or returned to baseline health characteristics, death, or referred to another hospital. the data were recorded by a trained physician in a checklist designed for this study. statistical analysis the data set was analyzed using the spss version 21. the qualitative variables were stated in percentage and quantitative variables were input as mean ± standard deviation. to evaluate the statistical difference of the studied factors between subgroups of each variable multinomial logistic regression was used. to determine the factors playing a role in patients’ death, after defining probable risk factors based on chi square, fisher's exact (for verbal qualitative variables) and kruskal–wallis test (for qualitative numerical variables), multivariable regression model was used. in all analyses p<0.05 was considered as significance level. results: 1000 patients suffering from tbi were evaluated (81.8% male; mean age 38.5 ± 21.7 years). frequency of individuals affected by head trauma in people aged 2060 (p < 0.001) and in spring (31.4%) was higher (p < 0.01). motorcycle accidents were the most common trauma mechanism in this study with 48.5% prevalence (p<0.001) and the least common mechanism was intentional damage (1.5%) (table 1). the mean gcs of patients was 9.94 ± 3.78 and 45.9% of them had a gcs of less than 9 (p<0.001). subdural hemorrhage (45.9%) epidural hemorrhage (23.7%) and intracranial hemorrhage accompanied by brain contusion (17.1%) were the most common findings of brain ct scans (p<0.001). the mean hospitalization duration was 7.52 ± 6.62 days. 721 (72.1%) patients were hospitalized for between 1 and 10 days, 194 patients between 11 and 20 days and 3 patients between 31 to 40 days. finally, table 1: demographic and basic variables of the patients in study variable frequency (%) p age 0-20 211 (21.1) <0.001 21-40 312 (31.2) ref 41-60 286 (28.6) 0.29 61-80 162 (16.2) <0.001 over 80 29 (2.9) <0.001 sex male 818 (81.8) ref female 182 (18.2) <0.001 place of residence the county 522 (52.2) ref the city 478 (47.8) 0.02 level of education uneducated 147 (14.7) <0.001 less than high school 258 (25.8) <0.001 high school diploma 465 (46.5) ref university degree 130 (13.0) <0.001 marital status single 435 (43.5) ref married 547 (54.7) <0.001 occupation self-employed 389 (38.9) ref unemployed 266 (26.6) <0.001 employee 207 (20.7) <0.001 housekeeper 86 (8.6) <0.001 other 52 (5.2) <0.001 reference season spring 314 (31.4) ref summer 250 (25.0) 0.007 fall 225 (22.5) <0.001 winter 211 (21.1) <0.001 mechanism of damage motorbike rider 485 (48.5) ref car accident 99 (9.9) <0.001 bike accident 21 (2.1) <0.001 falling 268 (26.8) <0.001 same level falling 112 (11.2) <0.001 intentional damage 15 (1.5) <0.001 accompanying injuries negative 591 (59.1) ref positive 409 (40.9) <0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 143 emergency (2015); 3 (4): 141-145 233 patients (23.3%) died while 745 (74.5%) recovered completely and were discharged. univariate analyses showed that over 60 years of age (36.4% vs. 20.9%), education less than high school diploma (32.1% vs. 24.4), being married (92.4% vs. 46.2%) and residing in rural areas (79.9% vs. 46.0%) had more prevalence in the dead patients while the prevalence of self-employed (14.1% vs. 34.7%) in this population was less than those who survived (table 4). in evaluating clinical factors, it was determined that motorcycle accidents and falling, a gcs of less than 9 (53.6% vs. 39.9%), needing surgery (54.9% vs.43.3%), subdural hemorrhage (54.5% vs. 44.6%) and intracranial hemorrhage accompanied by brain contusion (24.5% vs. 14.2%) were more common in the dead patients (table 5). the results of multiple variable regression analysis showed that, more than 60 years of age, trauma due to falling and motorcycle accidents, presence of intracranial hemorrhage accompanied by brain contusion, presence of subdural hemorrhage, gcs of less than 9 and the need to be admitted to intensive care unit were independent factors affecting the patients’ death (table 6). discussion: the results from this study showed the significant higher frequency of tbi in male, patients 20-60 years old, spring and motorcycle riders. it was seen that most patients had a decreased level of consciousness (gcs<9) and subdural and epidural hemorrhage were the most common findings of brain ct scan. prevalence of death was 23.3% in the present study. more than 60 years of age, trauma due to falling and motorcycle accidents, presence of intracranial hemorrhage accompanied by brain contusion, presence of subdural hemorrhage and gcs of less than 9 were independent risk factors of death. men’s employment in places outside home, justifies the greater extent of tbi in this sex. this finding is in accordance with other studies that have reported the ratio of head injuries in men to women to be 3 to 1 (10). in addition, in various international and regional studies tbi in men were reported more than women. although this ratio is changing in more recent studies and the percentage of women affected by tbi is rising. the reason is that women are using motor vehicles more than before and are participating in activities outside the house more table 2: level of consciousness and ct scan findings in the studied patients variable frequency (%) p level of consciousness (gcs score) 3-8 459 (45.9) ref 9-12 244 (24.4) <0.001 13-15 297 (29.7) <0.001 ct scan findings sdh 459 (45.9) ref edh 237 (23.7) <0.001 diffuse axonal injury 114 (11.4) <0.001 ich and brain contusion 171 (17.1) <0.001 simultaneous sdh and edh 19 (1.9) <0.001 sdh: subdural hemorrhage; edh: epidural hemorrhage ich: intracranial hemorrhage table 3: final outcome of the patients variable frequency (%) final outcome improved health 745 (74.5) deceased 233 (23.3) referral to another hospital 22 (2.2) need for surgery yes 454 (45.4) no 546 (54.6) hospitalization duration (days) 1-10 721 (72.1) 11-20 194 (19.4) 21-30 82 (8.2) 31-40 3 (0.3) admitting to intensive care unit yes 372 (37.2) no 628 (62.8) table 4: the relationship of demographic factors with patient outcome factor survived deceased p age under 60 628(79.1) 117 (63.6) <0.001 60 and over 166 (20.9) 67 (36.4) sex male 666 (81.6) (82.6) 0.75 female 150 (18.4) 32 (17.4) level of education uneducated 116 (14.2) 31 (16.8) <0.009 less than high school 199 (24.4) 59 (32.1) high school diploma 400 (49.0) 65 (35.3) university degree 101 (12.4) 29 (15.8) marital status single 439 (53.8) 14 (7.6) <0.001 married 377 (46.2) 170 (92.4) place of residence the county 375 (46.0) 147 (79.9) <0.001 the city 441 (54.0) 37 (21.1) occupation employee 230 (28.2) 57 (31.0) <0.001 self-employed 283 (37.4) 26 (14.1) housekeeper 55 (6.7) 31 (16.8) unemployed 248 (30.4) 18 (9.9) other 0 (0.0) 52 (28.3) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com monsef kasmaei et al 144 than before (11-14). plus, as stated before prevalence of tbi is more in the youth. this, is in agreement with the fact that generally, trauma and accidents in this group of age is more than other ages (2, 15). though the statistics in this study is not similar to the developing countries, it shows the same pattern. while a study in norway, showed that, the prevalence of tbi was more in people aged 0-4 years old and people older than 75 compared to other groups (13). this difference is due to the age distribution differenc e in the 2 countries, as average age in most developing countries is much less than that in developed countries and this can affect the pattern of epidemiologic characteristics of tbi. the pattern of trauma mechanism was also different in norway. in the afore-mentioned study, the most important cause of trauma was reported as falling but the most important cause in iran is road accidents. not using helmets is the main reason for the high prevalence of tbi in motorbike riders. so more preventive laws are needed in this regard. the results from wu et al. (11) and masson et al. (16) also show that motorcycle accident has the most prevalence in tbi and intentional damages were the least common. death prevalence in the studied patients was 23.3%. the statistics in other similar studies vary between 30-38% (17-19). although, roozenbeek et al. have reported that the prevalence of death in the patients with traumatic brain injury is between 31% and 51% in their review study. the researchers believe that this is due to differences in habits, lifestyle and health care in the populations. like death prevalence, death risk factors are also vastly different in the available reports (3). for instance, ducrocq et al. report that the existence of hypotension in the time of admission to the hospital, decreased gcs and higher injury severity score are independent risk factors for death in tbi (20). while hukkelhoven et al. demonstrate that aging is an independent risk fact or for death in these patients (21). in addition, tohme et al. introduce a fall in blood pressure and pre-hospital hypoxia as independent risk factors of death (22). the reason for these differences is that each study has paid attention to a different aspect. for example, tohme et al. have table 5: the relationship of clinical factors with patient outcome factor survived deceased p presence of accompanying injuries yes 331 (40.6) 78 (42.4) 0.65 no 485 (59.4) 106 (57.6) gcs level 3-8 221 (39.9) 238 (53.6) <0.001 9-12 152 (27.4) 92 (20.6) 13-15 181 (32.7) 116 (26.0) need for surgery yes 353 (43.3) 101 (54.9) 0.004 no 463 (56.7) 83 (45.1) ct scan findings epidural hemorrhage 195 (26.2) 28 (12.0) <0.001 subdural hemorrhage 332 (44.6) 127 (54.5) diffuse axonal injury 98 (13.2) 16 (6.9) simultaneous epidural and subdural hemorrhage 14 (1.9) 5 (2.2) intracranial hemorrhage and brain contusion 106 (14.2) 57 (24.5) the need to be admitted to intensive care unit yes 283(38.0) 89 (38.2) 0.95 no 462 (62.0) 144 (61.8) table 6: independent risk factors for the death of patients factor odds ratio 95% confidence interval p over 60 years of age 3.5 1.4-8.9 0.008 falling 5.0 1.8-14.3 0.002 motorcycle accident 9.4 5.4-17.5 <0.001 presence of subdural hemorrhage 12.1 5.0-29.4 <0.001 intracranial hemorrhage and brain contusion 6.1 2.2-16.7 <0.001 gcs of less than 9 2.5 1.2-5.3 0.02 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 145 emergency (2015); 3 (4): 141-145 concentrated on pre-hospital factors, while hukkelhoven et al. have paid more attention to the hospital and clinical aspects. therefore, each of the afore -mentioned studies (including this study) have missed some of the probable risk factors and more careful examination is needed in this field. a shortcoming regarding this study is that it was a retrospective study. studies on patients’ profiles is always accompanied by missed data due to a lack of records or careless recording of data. that is the reason why, many probable risk factors of death mentioned in the aforementioned studies like blood pressure level at the time of admission to hospital were not studied. but the simple random sampling used in this study makes it possible to generalize the findings to the whole popula tion. conclusion: this study’s findings demonstrated that tbi are more prevalent in people aged 20-60, male, spring and motorbike riders. it was also shown that the injury has been severe in most of them and subdural and epidural hemorrhage have been the most common findings of brain ct scans. the prevalence of death was 23.3% in this study. over 60 years of age, trauma due to falling and motorcycle accidents, presence of intracranial hemorrhage accompanied by brain contusion, presence of subdural hemorrhage and a gcs of less than 9 were independent risk factors for the death in these patients. acknowledgments: this article is derived from thesis of nastaran aziz zadeh roudpishi to give the doctorate degree of medicine from gilan university of medical sciences. we would like to say thanks to vice chancellor for research of medical faculty and those helped us to perform this project. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. world health organization. violence, injuries, and disability: biennial 2006–2007 report. geneva, switzerland: 2008. 2. saadat s, yousefifard m, asady h, jafari am, fayaz m, hosseini m. the most important causes of death in iranian population; a retrospective cohort study. emergency. 2014;3(1):16-21. 3. roozenbeek b, maas ai, menon dk. changing patterns in the epidemiology of traumatic brain injury. nat rev neurol. 2013;9:231-6. 4. leitgeb j, mauritz w, brazinova a, majdan m, wilbacher i. impact of concomitant injuries on outcomes after traumatic brain injury. arch orthop trauma surg. 2013;133(5):659-68. 5. greenwald bd, burnett dm, miller ma. congenital and acquired brain injury. 1. brain injury: epidemiology and pathophysiology. arch phys med rehabil. 2010;91(3):3-7. 6. park e, bell jd, baker aj. traumatic brain injury: can the consequences be stopped? cmaj. 2010;178(9):1163-70. 7. maas ai, stocchetti n, bullock r. moderate and severe traumatic brain injury in adults. lancet neurol. 2008;7(8):72841. 8. híjar m1, pérez-núñez r, inclán-valadez c, silveirarodrigues em. road safety legislation in the americas. rev panam salud publica. 2012 32(1):70-6. 9. asadi p, kasmaie vm, zohrevandi b, ziabari smz, marzbani bbmb. disposition of patients before and after establishment of emergency medicine specialists. iran j emerg med. 2014;1(1):28-33. 10. fakharian e, fazel mr, tabesh h, nabavi z. incidence of mild head injury, management, and expenses in kashan, 20032004. feyz j kashan uni med sci. 2007;11(3):21-6. [in persian]. 11. wu x, hu j, zhuo l, et al. epidemiology of traumatic brain injury in eastern china, 2004: a prospective large case study. j trauma. 2008;64(5):1313-9. 12. chiu w-t, huang s-j, tsai s-h, et al. the impact of time, legislation, and geography on the epidemiology of traumatic brain injury. j clin neurosci. 2007;14(10):930-5. 13. andelic n, sigurdardottir s, brunborg c, roe c. incidence of hospital-treated traumatic brain injury in the oslo population. neuroepidemiology. 2008;30(2):120-8. 14. mcgarry lj, thompson d, millham fh, et al. outcomes and costs of acute treatment of traumatic brain injury. j trauma. 2002;53(6):1152-9. 15. faul m, xu l, wald m, coronado vg. traumatic brain injury in the united states: emergency department visits, hospitalizations and deaths 2002–2006. atlanta, ga: centers for disease control and prevention, national center for injury prevention and control. 2010:2-70. 16. masson f, thicoipe m, aye p, et al. epidemiology of severe brain injuries: a prospective population-based study. j trauma. 2001;51(3):481-9. 17. kleiven s, peloso pm, holst h. the epidemiology of head injuries in sweden from 1987 to 2000. inj control saf promot. 2003;10(3):173-80. 18. steudel w, cortbus f, schwerdtfeger k. epidemiology and prevention of fatal head injuries in germany–trends and the impact of the reunification. acta neurochir (wien). 2005;147(3):231-42. 19. maegele m, engel d, bouillon b, et al. incidence and outcome of traumatic brain injury in an urban area in western europe over 10 years. eur surg res. 2007;39(6):372-9. 20. ducrocq sc, meyer pg, orliaguet ga, et al. epidemiology and early predictive factors of mortality and outcome in children with traumatic severe brain injury: experience of a french pediatric trauma center. pediatr crit care med. 2006;7(5):461-7. 21. hukkelhoven cw, steyerberg ew, rampen aj, et al. patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients. j neurosurg. 2003;99(4):666-73. 22. tohme s, delhumeau c, zuercher m, haller g, walder b. prehospital risk factors of mortality and impaired consciousness after severe traumatic brain injury: an epidemiological study. scand j trauma resusc emerg med. 2014;22(1):1-10. introduction: methods: study design and setting participants studied variables statistical analysis results: discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: emergency. 2017; 5 (1), e58 or i g i n a l re s e a rc h prevalence and associated factors of acute traumatic coagulopathy; a cross sectional study hojjat derakhshanfar1, ali vafaei2, ali tabatabaey3∗, shamila noori4 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shahid beheshti hospital, qom university of medical sciences, qom, iran. 4. pathology department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: december 2016; accepted: february 2017; published online: 24 february 2017 abstract: introduction: acute traumatic coagulopathy (atc) is defined as having evidence of coagulopathy in patients with severe trauma. the aim of this preliminary study was to assess the prevalence and associated factors of atc in severely traumatic patients presenting to emergency department (ed). methods: in this retrospective cross sectional study, all patients with severe traumatic injury and available coagulation profile, presenting to the eds of two major trauma centers in tehran, iran, during one year, were studied. rate of atc was determined and the associations with various variables as well as outcome were analyzed using spss 21. results: 246 patients with the mean age of 36.57±17.11 years were included (88.2% male). the mean injury severity score (iss) was 21.83 ± 7.37 (16 – 54). patients were resuscitated with 676.83 ± 452.02 (0 – 1500) ml intravenous fluid before arriving at the ed. the maximum and minimum frequencies of atc were 31.3% based on ptt > 36s and 2.4% based on pt > 18s, respectively. there was a significant association between the occurrence of atc (pt ratio > 1.2) and iss > 23 (p = 0.001), abdominal abbreviated injury score (ais) > 3 (p = 0.003), base deficit > 4 (p = 0.019), pulse rate > 90/minute (p = 0.041), and ph < 7.30 (p = 0.043). conclusion: the frequency of atc in the present series varied from 2.4% to 31.3% based on different atc definitions. abdominal ais > 3 and base deficit > 4 were among the significant independent factors related to atc occurrence based on stepwise logistic regression analysis. keywords: blood coagulation disorders; multiple trauma; risk factors; emergency service, hospital; outcome assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: derakhshanfar h, vafaei a, tabatabaey a, noori sh. prevalence and associated factors of acute traumatic coagulopathy; a cross sectional study. emergency. 2017; 5(1): e58. 1. introduction o ne third of trauma related deaths are due to hemorrhage, which are generally preventable (1). acute traumatic coagulopathy (atc) is defined as having evidence of coagulopathy in patients with severe trauma on admission to emergency department (ed). the term atc was first introduced in 2003 (2) and recent studies indicated that this abnormality is an endogenous phenomenon, which starts before any intervention (3). this characteristic separates this entity from the better known dilution coagulopathy or consumption coagulopathy in trauma patients. ∗corresponding author: ali tabatabaey; emergency department, shahid beheshti hospital, shahid beheshti blv, qom, iran. postal code: 3719964797 tel: +98-25-36122000; email: atabatabaey@muq.ac.ir it is estimated that up to 25% of severely injured patients have atc. these patients have four-fold increased risk of mortality and significantly greater transfusion requirement (4). more importantly, it has been suggested that management strategies targeting atc may result in significant improvement of outcomes (1). many attempts have been made for diagnosing atc in the early minutes of admission to ed (1, 5, 6). unfortunately, currently available laboratory methods do not have the capability of early atc diagnosis. therefore, researchers have sought to find clinical factors for early prediction of atc occurrence, which is vital for initiation of lifesaving treatments (7, 8). risk stratification of patients based on clinical findings and quick-available laboratory studies could help in early recognition of patients at risk for developing atc. the aim of this preliminary study was to assess the prevalence and associated factors of atc in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. derakhshanfar et al. 2 severely traumatic patients admitted to ed. 2. methods 2.1. study design and setting in this retrospective cross sectional study, the patients with severe traumatic injury presenting to the eds of two major trauma centers in tehran, iran (shohadye tajrish and imam hossein hospitals), during march 2013 to march 2014 were studied. this study was approved by the ethical committee of shahid beheshti university of medical sciences, and the authors have done the study based on the declaration of helsinki. 2.2. participants the medical profiles of all patients with available coagulation panel samples, which were admitted to the trauma units of the mentioned hospitals during the study period, were retrospectively evaluated. all patients with severe injury were included. severe injury was defined as injury severity score (iss) more than 15 (9). patients less than 18 years old and subjects with history of bleeding disorder, severe liver dysfunction, and using anticoagulation medications within the last two weeks were excluded. moreover, in order to exclude patients at risk of dilution coagulopathy, those who had received more than 2 liters of fluids during transport and those who had been referred from other treatment centers were also excluded from the study. 2.3. data gathering demographic variables (age and gender), trauma mechanism, presenting vital signs (blood pressure, respiratory rate, pulse rate, temperature, o2 saturation), injured body parts, trauma severity based on iss, laboratory findings (coagulation profile, cell blood count, and blood gas analysis), as well as in hospital outcomes of the patients (mortality, need for icu admission, need for surgery, and need for blood transfusion) were extracted and collected from the patients’ profile using a predesigned checklist. coagulation profile consisted of prothrombin time (pt), partial thromboplastin time (ptt), pt ratio (patient pt/control pt), and international normalization ration (inr). a senior emergency medicine resident, under supervision of an emergency medicine specialist, was responsible for review of patients’ medical profile and data gathering. 2.4. atc definition previous studies have used different definitions for atc. the current available definitions are: pt more than 18s, ptt more than 36s (5), pt ratio greater than 1.2 (1, 10), or international normalization ration (inr) greater than 1.5 (7, 8). all four table 1: baseline characteristics and outcome of the study population variables value gender male 216 (88.2) female 29 (11.8) mechanism of injury pedestrian 33 (13.4) motorcycle 83 (33.7) car 48 (19.5) rollover 20 (8.1) falling 47 (19.1) assault 10 (4.1) others 5 (2.0) transport to hospital ambulance 173 (70.3) unknown 10 (4.1) self-admission 63 (25.6) glasgow coma scale 15 146 (60.6) 8 15 74 (30.7) < 8 21 (8.7) presenting vital signs systolic blood pressure (mmhg) 116.45 ± 17.74 respiratory rate (/minutes) 17.63 ± 2.78 pulse rate (/minutes) 89.46 ± 15.06 saturation o2 9%) 94.38 ± 5.33 temperature (c) 37.3 ± 0.40 outcome need for blood products 39 (15.9) need for icu admission 103 (42) need for surgical intervention 192 (78) mortality 20 (8.1) data were presented as mean ± standard deviation or frequency and percentage. available definitions were used in the present study and the frequency of atc was individually determined based on each of the mentioned definitions. a combination of the definitions was also considered, i.e. any patient who met any of the criteria was considered to have trauma related coagulopathy. 2.5. statistical analysis the data were analyzed using spss version 21 and presented as mean ± standard deviation (sd) or frequency and percentage. the association between different atc definitions and measured outcomes were evaluated. then, the association between atc occurrence (based on pt ratio > 1.2) and baseline variables was assessed. continuous variables were compared using mann-whitney u test, and categorical data were analyzed using chi-square test. after recognition of statically significant variables, clinically relevant cut-points were assigned to these variables to make their use more feasible in the clinical setting. finally, logistic regression analysis was employed to determine the independent related factors of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1), e58 atc occurrence. 3. results 3.1. baseline characteristics 246 patients with the mean age of 36.57±17.11 (18 – 88) years were included (88.2% male). table 1 shows the baseline characteristics and outcome of the study population. motorcycle accidents were the most frequent mechanism of injury (33.7%) and 70.4% of patients had gcs 15 at the time of presenting to ed. the mean severity of injury based on iss was 21.83 ± 7.37 (16 – 54). patients were resuscitated with 676.83 ± 452.02 (0 – 1500) ml intravenous fluid before arriving at the ed. the mean duration of ed stay was 9.38 ± 9.83 (0.5 – 67) hours. 3.2. atc (frequency and associations) frequency of atc based on different predefined definitions and its association with measured outcomes is presented in table 2. the maximum and minimum frequencies of atc were 31.3% based on ptt > 36s and 2.4% based on pt > 18s, respectively. none of the definitions was able to predict in-hospital mortality. table 3 summarizes the results of univariate analysis between atc and different baseline variables. there was a significant correlation between the occurrence of atc (pt ratio > 1.2) and iss > 23 (p = 0.001), abdominal ais > 3 (p = 0.003), base deficit > 4 (p = 0.019), pulse rate > 90 (p = 0.041), and ph < 7.30 (p = 0.043). based on the results of a stepwise logistic regression analysis abdominal ais > 3 (p = 0.001) and base deficit > 4 (p = 0.011) were independent related factors of atc occurrence. 4. discussion the frequency of atc in the present series varied from 2.4% (pt > 18s) to 31.3% (ptt > 36s) based on different atc definitions. abdominal ais > 3 and base deficit > 4 were among the significant independent related factors of atc occurrence. a high prevalence of atc has been reported in uganda with 54% (5), while an australian study found that only 9.0% of their traumatic patients met the definition of traumatic coagulopathy (8). two studies from europe have reported the prevalence of atc in the range of 24% to 34% (2, 11). most studies have shown a significant association between the presence of atc and mortality (2, 3, 5, 8, 12). this was not the case in this study. neither the four definitions used for atc, nor their combination, were able to predict mortality. we believe this was in part due to the low rate of mortalities in our study, which greatly limited its power to find an association between coagulation tests and mortality. occurrence of atc, successfully predicted the necessity for intensive care, and requirement of blood products transfusion. more transfusion and resuscitation requirements are other widely accepted predictable outcomes of atc (7, 13, 14), yet they are not universal (5). in our study, having atc would strongly predict higher transfusion requirements. genetic factors are well-known contributors to the occurrence of atc (7, 11); so, the study of this phenomenon in different settings may further expand our understanding of the contributing factors. this has been a longtime interest of researchers since the coagulation profile is rarely made available in the early minutes of ed admission (1). in the absence of a rapid diagnostic tool, management of atc is currently relying on suboptimal empirical transfusion strategies (14-17). in an attempt to predict the occurrence of atc before availability of coagulation profile, mitra et al. introduced the coagulopathy of severe trauma (coast) score to help in early diagnosis of atc. the researchers found that scores equal to or greater than 3 are predictive of atc with appropriate sensitivity and specificity (8). in another study in germany, yucel et al. developed a more complicated scoring system aiming to predict atc and the need for massive transfusion. in the trauma associated severe hemorrhage (tash) score system, items such as hemoglobin, base excess, systolic blood pressure, heart rate, confirmed free intra-abdominal fluid, instable pelvic fracture, femur fracture, and male gender are contributing (18). a tash score greater than 16 has been suggested as the cut-point for prediction of atc. other studies have also searched for clinical risk factors of atc. abdominal and thoracic trauma, pelvic fractures, mechanism of injury, and evidence of anemia and shock have been suggested as the risk factors for atc (7, 19). the importance of male gender has also been emphasized (13, 20). in this study, although no association was found between atc and gender, significant and independent associations were recognized with grade of abdominal trauma, and a base deficit greater than 4. this is in accordance with previous findings, which stated that coagulopathy is more prevalent when severe injury and hypo perfusion are co-existing (21-23). a prospective multi-center cohort study is suggested as the next step for evaluating atc. 5. limitation this was a preliminary attempt for estimating the prevalence and also recognizing the associated factors of atc in iran. the retrograde design of the study predisposes it to several limitations. the most important limitation was incomplete coverage of the target population and having missing data. we selected patients for whom a coagulation panel had been ordered by physicians in the primary order. we believe that since these tests are generally ordered for severely injured this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. derakhshanfar et al. 4 table 2: association of acute traumatic coagulopathy occurrence and patients’ outcomes variables number (%) outcomes mortality icu surgery transfusion pt > 18s 6 (2.4) + ptt > 36s 77 (31.3) + pt ratio > 1.2 28 (11.4) + + inr > 1.5 27 (11) + + combination 94 (38.2) + pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio; icu: need to admission in intensive care unit; +: means statistically significant association. table 3: association of acute traumatic coagulopathy (atc) occurrence and different baseline variables variable atc p with (n=28) without (n=218) male gender 192 (88) 24 (86) 0.670 age (year) 32.25 ± 13.74 37.12 ± 17.44 0.221 transport time (minute) 42.30 ± 39.49 36.34 ± 28.70 0.824 intravenous fluids (ml) 767.86 ± 419.04 665.14 ± 455.66 0.237 injury severity score 25.75 ± 9.312 21.33 ± 6.95 0.017 head and neck ais 1.71 ± 1.94 2.09 ± 1.90 0.365 face ais 0.57 ± 1.20 0.66 ± 1.13 0.519 thorax ais 1.07 ± 1.65 0.98 ± 1.44 0.996 abdomen ais 2.07 ± 1.96 1.03 ± 1.48 0.004 extremities ais 1.61±1.77 1.56 ± 1.80 0.884 external ais 0.39 ± 0.86 0.14 ± 0.52 0.083 presenting vital signs glasgow coma scale 12.75±3.00 13.44±3.01 0.139 sbp (mmhg) 100.32±17.48 117.25±17.66 0.029 respiratory rate (/minute) 95.07±12.58 88.73±15.23 0.004 temperature (c) 37.00±0.32 37.04±0.42 0.905 respiratory rate (/minute) 18.68±4.25 17.49±2.52 0.199 o2 saturation in the ed 92.70±4.94 94.59±5.36 0.014 laboratory findings serum ph 7.31±0.13 7.38±0.12 0.044 paco2 (mmhg) 40.85±14.62 39.92±11.17 0.788 hco3 19.91±5.62 23.88±8.67 0.047 base deficit 5.47±5.61 1.41±6.99 0.026 white blood cell (103/µl) 14.03±5.17 12.15k±4.59 0.034 platelet count (103/µl) 170.18±88.32 192.53±84.87 0.119 hemoglobin (mg/dl) 11.51±2.69 12.12±2.79 0.230 data were presented as mean ± standard deviation or number and percentage. ais: abbreviated injury score; sbp: systolic blood pressure. patients and those who require operative interventions, we most likely have not missed a large portion of our target population. the low rate of mortality in our studied sample might be owing to selection bias; in which the test results of patients with early mortality might not have been included in their medical profile, leading to elimination from this study. another more possible explanation for the low reported mortality might be a high incidence of pre-hospital mortality. it has been reported that, in developing countries, more than 70% of deaths due to injuries occur on the scene (21). in such settings most early mortalities never reach hospital-based studies. 6. conclusion the frequency of atc in the present series varied from 2.4% (pt > 18s) to 31.3% (ptt > 36s) based on different atc definitions. abdominal ais > 3 and base deficit > 4 were among the significant independent factors related to atc occurrence based on stepwise logistic regression analysis.this reinforces the concept that acute traumatic coagulopathy is triggered when severe injury and hypoperfusion coexist. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1), e58 7. appendix 7.1. acknowledgements this work has been excerpted from the residency thesis number 216, by ali tabatabaey md, supervised by hojjat derakhshanfar md at the school of medicine, shahid beheshti university of medical sceinces, tehran, iran. 7.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. davenport r, manson j, de’ath h, platton s, coates a, allard s, et al. functional definition and characterization of acute traumatic coagulopathy. crit care med. 2011;39:2652-8. 2. brohi k, singh j, heron m, coats t. acute traumatic 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ganter mt, pittet j-f. new insights into acute coagulopathy in trauma patients. best practice & research clinical anaesthesiology. 2010;24:15-25. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e33 or i g i n a l re s e a rc h sustained return of spontaneous circulation following out-of-hospital cardiac arrest; developing a predictive model based on multivariate analysis thongpitak huabbangyang1, agasak silakoon1, pramote papukdee1∗, rossakorn klaiangthong1, chaleamlap thongpean2, wannakorn pralomcharoensuk2, weerawan khaokaen2, sunisa bumrongchai2, ratree chaisorn3, chomkamol saumok3 1. department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok, thailand. 2. faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. 3. division of division of emergency medical service and disaster, faculty of medicine vajira hospital, navamindradhiraj university, bangkok, thailand. received: february 2023; accepted: march 2023; published online: 27 april 2023 abstract: introduction: identifying the predictive factors of sustained return of spontaneous circulation (rosc) following out-ofhospital cardiac arrest (ohca) will be helpful in management of these patients. this study aimed to develop a predictive model in this regard. methods: in a retrospective observational study, data of adult patients with ohca, were collected from vajira emergency medical services patient care report. multiple logistic regression analysis with a regression coefficient was used to develop a predictive score for a sustained rosc at the scene. area under the receiver operating characteristic (roc) curve (auc) was used to validate the accuracy of the predictive score for a sustained rosc. results: independent factors associated with a sustained rosc included cardiopulmonary resuscitation (cpr) duration < 30 min (adjusted odds ratio (aor)= 5.05, 95% confidence interval (ci): 3.34–7.65; p < 0.001); advanced airway management with an endotracheal tube (aor= 3.06, 95% ci: 1.77–5.31; p < 0.001); advanced airway management with laryngeal mask airway (aor= 3.42, 95% ci: 1.02–11.46; p = 0.046); defibrillation (aor = 2.05, 95% ci: 1.31–3.2; p = 0.002); capillary blood glucose (cbg) level < 150 mg% (aor= 1.95, 95% ci: 1.05–3.65; p = 0.035); cbg at least 150 mg% (aor= 2.87, 95% ci: 1.56–5.29; p = 0.001); pupil reflex (aor = 2.96, 95% ci: 1.1–7.96; p = 0.032); and response time at most 8 min (aor= 1.66, 95% ci: 1.07–2.57; p = 0.023). these were developed into the pupil reflex, response time, advanced airway management, defibrillation, cbg, and cpr duration (prad-ccpr) score. the most accurate cutoff point of score using youden’s index was ≥ 6 with auc of 0.759 (95% ci: 0.715–0.802; p < 0.001), sensitivity of 62.0% (95% ci: 51.2–71.9%), specificity of 75.7% (95% ci: 69.4–81.2%), positive predictive value of 51.8% (95% ci: 40.9–62.3%), and negative predictive value of 79.5% (95% ci: 73.5–84.6%). conclusion: an optimal prad-ccpr score of ≥ 6 provides an acceptable accuracy of 0.759 with sensitivity of 62.0% and specificity of 75.7% in prediction of sustained rosc following ohca. this predictive score might help cpr commanders to prognosticate the outcome of patients with ohca at the scene. keywords: emergency medical services; out-of-hospital cardiac arrest; heart arrest; return of spontaneous circulation cite this article as: ersin altınsoy k, murat oktay m. sustained return of spontaneous circulation following out-of-hospital cardiac arrest; developing a predictive model based on multivariate analysis. arch acad emerg med. 2023; 11(1): e33. https://doi.org/10.22037/aaem.v11i1.2012. ∗corresponding author: pramote papukdee; department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, bangkok 10400, thailand. tel: +66 2-244-3000, email: pramote@nmu.ac.th, orcid: https://orcid.org/0000-0002-3644-3925. 1. introduction out-of-hospital cardiac arrest (ohca) is a medical emergency condition requiring immediate management to save lives and an important global cause of death, especially in middle-income or developing countries. the reported number of the deceased due to cardiac arrest was a million per year (1). the worldwide prevalence was 50–60 per 100,000 populations (2). in the usa, the incidence in adults was more this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 2 than 350,000 per year, the survival rate was 10.8%, and only 9% had favorable neurological outcomes (3). the prevalence rates of 17–128 and 21–29 per 100,000 population in central america and asia, respectively, were reported in a previous study (4). in thailand, the survival rate of patients with ohca at the scene, resuscitated by emergency medical services (ems), was 25.6% (5). according to the report of the pan asian resuscitation outcomes study (paros) in thailand, the survival rate was 4.0% (6), indicating that patients with ohca have different outcomes based on each context of each country, such as differences in the study design, sample size, and demographic data, especially hospital data including prehospital management by ems and management in the hospital (7). a systematic review and meta-analysis showed that patients having ohca with shockable rhythm had better survival outcomes than those with non-shockable rhythm (8). bystander cardiopulmonary resuscitation (bystander cpr) and bystander automated external defibrillator (aed) significantly improved the survival outcomes of patients with ohca (9). previous studies have demonstrated that predictive factors for a sustained return of spontaneous circulation (sustained rosc) included trauma cause (5, 10), response time (5, 11), bystander cpr (11), time to first chest compression (7), younger age (12), arrest in a public area (12), witnessed arrest (12), and shockable rhythm (12). to the authors’ knowledge, three studies have developed predictive scores for a sustained rosc, namely, watch-cpr score (7), raca score (13), null-please score (14), and prosc (15). all previous studies have developed predictive scores in the context of management in the hospital or emergency department, which was difficult to apply in prehospital practice and lacked data on the time and treatment of patients at the scene, which are important in the prehospital context. some studies have used laboratory data, which could not be applied in the prehospital context. however, a modeling study for the prediction of sustained rosc of patients with ohca at the scene would help paramedics and emergency nurse practitioners manage patients with ohca, ethically. thailand is a middle-income country, and no emergency physicians are working with ambulances at the scene in many areas (10). resources are substantially limited in the prehospital context compared with the management at the emergency department. an important issue is how to efficiently resuscitate with the best outcome and lowest cost. therefore, this study aimed to develop and validate a predictive model for a sustained rosc of patients with ohca at the scene. 2. methods 2.1. study design and settings this retrospective observational study was conducted in vajira emergency medical service (v-ems), vajira hospital, faculty of medicine, navamindradhiraj university, bangkok, thailand, between january 1, 2019, and july 31, 2022. v-ems was a leader of ems unit zone area 1 from a total of nine area divisions of ems in bangkok, dispatched from erawan center, bangkok, networking with public and private hospitals, a total of six hospitals, in an area of 50 km2 with 500,000 population (5, 10). during a response operation for patients with ohca, the ems team sent by v-ems included at least three personnel (a paramedic or emergency nurse practitioner (enps) as operation team leader, and two emergency medical technicians. in each response operation, paramedics or enps would operate under offline and online medical protocols under the orders of emergency physicians (eps). in patients with cardiac arrest, the american heart association guidelines of 2020 were applied. all team members had passed advanced cardiovascular life-support training. the standards for the reporting of observation studies in epidemiology (strobe) statement were applied (16). 2.2. participants data of adult patients (aged > 18 years) with ohca were collected from ems patient care report, coded with the thailand emergency medical triage protocol and criteria-based dispatch (cbd) symptom group 6, which is cardiac arrest, managed by the v-ems unit, vajira hospital, faculty of medicine, navamindradhiraj university, bangkok, thailand, between january 1, 2019, and july 31, 2022. the patients were managed in accordance with advanced cardiovascular life support (acls) based on cpr guidelines (17, 18). patients with incomplete or missing data, signs of irreversible death so that based on the judgement of the team leader no resuscitation was performed, do-not-resuscitate orders, cardiac arrest outside the scene, ohca during transfer, i.e., patients with ohca receiving cpr starting at the scene and continuing during hospital transfer, and termination of resuscitation at the scene were excluded. 2.3. data collection data of patients with ohca were collected from the ems patient care report, which was a record of advanced ems operation, bangkok ems (erawan center), and the standard form and unit in the bangkok advanced emergency operation unit. this form contained data of ems operation units, patients, and all treatments by ems teams, recorded by dispatchers and paramedics or enps operating at the scene. these data this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e33 figure 1: receiver operating characteristic (roc) curves for the predictive model of sustained return of spontaneous circulation among patients with out-of-hospital cardiac arrest at the scene: (a) derivation set and (b) validation set. auroc: area under the roc curve. were a part of the remuneration for ems operation units. all data were filled in and recorded in microsoft excel by a principal investigator. data comprised general characteristics of patients with ohca including sex, age, comorbidities, location type, witnessed arrest, bystander cpr, arrest type, type of traumatic arrest, type of non-traumatic arrest, time from arrest to chest compression, cpr duration, advanced airway management, defibrillation, fluid resuscitation, medication during cpr, capillary blood glucose (cbg), pupil reflex, response time, and sustained rosc at the scene. 2.4. definitions the sustained rosc was determined when chest compressions were not required for 20 minutes, and signs of circulation persisted for at least 20 minutes (7). symptom group 6 was defined as ohca according to the emergency level screening system of thailand, classified according to cbd 6, severity level–critical (red) 6 critical 1 or 6 red 1, defined as cardiac arrest including unconsciousness, apnea, or pulselessness (5). response time was defined as the duration from the emergency call to ambulance arrival at the scene (5). the time from arrest to chest compression was defined as the interval between sudden cardiac collapse to chest compression by a bystander. cpr duration was defined as the duration from the first medical contract (fmc) to the end of cpr based on the ems patient care report. the derivation set was defined as a new dataset used by the authors to develop the predictive score for a sustained rosc of patients with ohca at the scene. the validation set was defined as the dataset used to validate the accuracy of the predictive score for a sustained rosc of patients with ohca at the scene. 2.5. sample size determination the main objective of this study was to develop a predictive score for a sustained rosc in patients with ohca at the scene using multiple logistic regression analysis. sample size estimation relied on multiple logistic regression analysis using the number of events per variable in a logistic regression analysis (19). the analysis required enough samples to include at least 10 interesting events for each independent variable. at most, 15 variables in the development of the predictive score for a sustained rosc were expected. the number of samples with interesting events, which was sustained rosc, of 150 events/samples was required. the rate/incidence of sustained rosc was 25.6%. therefore, the total sample size for analysis was at least 586 ((150*100)/25.6 = 586). after 5% of the sample size was added using the formula (nnew = 586/[1 – 0.05]), the required sample size was calculated to be at least 617. thus, the sample size for the development of the predictive score for a sustained rosc was 620. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 4 for the sample size estimation to validate the accuracy of the predictive score (validation set), the ratio of the sample size to the sample size during the development of the score (derivation set) was 1:2. thus, sample sizes for the derivation and validation sets were 620 and the 310, respectively. hence, the final sample size in the present study was 930, and simple random sampling was used. 2.6. statistical analysis a descriptive analysis was performed to examine the variable distribution. continuous variables are presented as mean ± standard deviation (sd) or median and interquartile range (iqr), and categorical variables are presented as frequencies and proportions. when comparing the two groups, differences were evaluated using independent t-test or mann–whitney u test for numeric variables and chisquare test or fisher’s exact test for categorical variables. in the development of the predictive score, multivariable analysis with multiple logistic regression analysis and a backward stepwise selection method were used. all statistical tests were considered statistically significant at p < 0.05. significant factors associated with a sustained rosc were obtained from the univariable analysis. regression coefficient, odds ratio (or), and 95% confidence intervals (ci) were reported. the predictive score was developed using the regression coefficient. the accuracy of the predictive score was validated using receiver operating characteristic (roc) curve and area under the curve (auc), using youden’s index to determine the best cutoff point. sensitivity, specificity, accuracy, positive predictive value (ppv ), negative predictive value (npv ), and area under the roc curve were reported with 95% ci. ibm spss statistics for windows, version 28.0 (ibm corp., armonk, ny, usa) and stata version 13.0 (statacorp, college station, tx, usa) were used. all statistical tests were considered statistically significant at p < 0.05. 2.7. ethical statement this study was conducted in accordance with the tenets of the declaration of helsinki 1975 and its revisions in 2000. it was approved by the institutional review board of the faculty of medicine vajira hospital, navamindradhiraj university (coa no. 217/2565). informed consent requirement was waived because of the retrospective nature and anonymity of all patient data. 3. results 3.1. characteristics of patients in derivation set 620 cases were studied (66.0% male). table 1 compares the baseline characteristics of patients between cases with and without sustained rosc. the two groups had significant differences regarding cpr duration (p < 0.001), advanced airway management (p = 0.001), defibrillation (p < 0.001), the median concentrations of cbg (p < 0.001), pupil reflex (p < 0.001), and response time (p = 0.030). 3.2. developing the predictive model based on multivariate analysis using multiple logistic regression analysis and backward stepwise selection method, independent associated factors of sustained rosc of patients with ohca at the scene were: cpr duration < 30 min (aor = 5.05, 95% ci: 3.34–7.65; p < 0.001); airway management at the scene with endotracheal tube (ett) (aor = 3.06, 95% ci: 1.77–5.31; p < 0.001) or laryngeal mask airway (lma) (aor = 3.42, 95% ci: 1.02–11.46; p = 0.046); defibrillation (aor = 2.05, 95% ci: 1.31–3.2; p = 0.002); cbg level < 150 mg% (aor= 1.95, 95% ci: 1.05–3.65; p = 0.035); cbg at least 150 mg% (aor = 2.87, 95% ci: 1.56–5.29; p = 0.001); had pupil reflex (aor = 2.96, 95% ci: 1.1–7.96; p = 0.032); had response time at most 8 min (aor = 1.66, 95% ci: 1.07–2.57; p = 0.023) (table 2). the analyzed results of the predictive formula for a sustained rosc of patients with ohca at the scene in the form of logit transformation were used to develop the predictive score using a regression coefficient. cpr duration < 30 min was assigned 3 points; advanced airway management with ett, 2 points; advanced airway management with lma, 2.5 points; defibrillation, 1.5 points; cbg <150 mg%, 1 point; cbg ≥150 mg%, 2 points; pupil reflex, 2 points; and response time ≤ 8 min, 1 point. the total score ranged from 0 to 15 points. the predictive score could predict sustained rosc of patients with ohca at the scene significantly with auc of 0.759 (95% ci 0.715–0.802; p < 0.001). 3.3. validation of model 310 cases were studied (65.8% male). table 1 compares the baseline characteristics of patients between patients with and without sustained rosc in the validation set. using the validation dataset with 310 patients, the predictive score could significantly predict sustained rosc of patients with ohca at the scene, with auc of 0.732 (95% ci 0.673–0.792, p < 0.001). the predictive score of at least 6 had the highest youden’s index (0.377), which was the most suitable point in the prediction of sustained rosc among patients with ohca at the scene, with sensitivity of 62.0% (95% ci: 51.2–71.9), specificity of 75.7% (95% ci: 69.4–81.2), ppv of 51.8% (95% ci: 40.9–62.3), and npv of 79.5% (95% ci: 73.5–84.6) (table 3 and figure 1). 4. discussion first, in this study, the incidence of sustained rosc at the scene was 42.5% in patients with ohca resuscitated by ems in thailand, which is a middle-income country, like the prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e33 table 1: characteristics of patients with out-of-hospital cardiac arrest with and without sustained return of spontaneous circulation (rosc) in derivation and validation sets characteristics derivation set (n = 620) p-value validation set (n = 310) p-value total sustained rosc death total sustained rosc death) (n = 620) (n = 177) (n = 443) (n = 310) (n= 218) (n = 92) sex male 409 (66.0) 112 (63.3) 297 (67.0) 0.371 204 (65.8) 60 (65.2) 144 (66.1) 0.887 female 211 (34.0) 65 (36.7) 146 (33.0) 106 (34.2) 32 (34.8) 74 (33.9) age (year) mean ±sd 63.86 ± 18.26 62.37 ± 18.08 64.46 ± 18.32 0.197 63.14 ± 18.99 62.77 ± 19.11 63.29 ± 18.99 0.827 comorbidities hypertension 153 (24.7) 44 (24.9) 109 (24.6) 0.947 73 (23.5) 21 (22.8) 52 (23.9) 0.846 diabetes mellitus 130 (21.0) 38 (21.5) 92 (20.8) 0.846 55 (17.7) 19 (20.7) 36 (16.5) 0.384 heart disease 116 (18.7) 42 (23.7) 74 (16.7) 0.043 56 (18.1) 20 (21.7) 36 (16.5) 0.275 dyslipidemia 29 (4.7) 7 (4.0) 22 (5.0) 0.590 11 (3.5) 1 (1.1) 10 (4.6) 0.184 respiratory disease 87 (14.0) 10 (5.6) 77 (17.4) <0.001 53 (17.1) 7 (7.6) 46 (21.1) 0.004 stroke 7 (1.1) 4 (2.3) 3 (0.7) 0.107 6 (1.9) 2 (2.2) 4 (1.8) 1.000 renal diseases 29 (4.7) 9 (5.1) 20 (4.5) 0.761 17 (5.5) 7 (7.6) 10 (4.6) 0.286 cancer 12 (1.9) 6 (3.4) 6 (1.4) 0.111 8 (2.6) 4 (4.3) 4 (1.8) 0.243 other 19 (3.1) 7 (4.0) 12 (2.7) 0.416 12 (3.9) 6 (6.5) 6 (2.8) 0.193 location type non-public 509 (82.1) 146 (82.5) 363 (81.9) 0.873 242 (78.1) 69 (75.0) 173 (79.4) 0.397 public 111 (17.9) 31 (17.5) 80 (18.1) 68 (21.9) 23 (25.0) 45 (20.6) witnessed arrest no 310 (50.0) 96 (54.2) 214 (48.3) 0.182 131 (42.3) 38 (41.3) 93 (42.7) 0.825 yes 310 (50.0) 81 (45.8) 229 (51.7) 179 (57.7) 54 (58.7) 125 (57.3) bystander cpr no 315 (50.8) 99 (55.9) 216 (48.8) 0.107 144 (46.5) 47 (51.1) 97 (44.5) 0.288 yes 305 (49.2) 78 (44.1) 227 (51.2) 166 (53.5) 45 (48.9) 121 (55.5) type of arrest non-trauma 587 (94.7) 168 (94.9) 419 (94.6) 0.868 293 (94.5) 87 (94.6) 206 (94.5) 0.980 trauma 33 (5.3) 9 (5.1) 24 (5.4) 17 (5.5) 5 (5.4) 12 (5.5) type of traumatic arrest (n = 50) blunt 28 (84.8) 8 (88.9) 20 (83.3) 1.000 15 (88.2) 3 (60.0) 12 (100.0) 0.074 penetrating 5 (15.2) 1 (11.1) 4 (16.7) 2 (11.8) 2 (40.0) 0 (0.0) type of non-traumatic arrest (n = 880) non-cardiogenic 312 (53.2) 62 (36.9) 250 (59.7) <0.001 159 (54.3) 28 (32.2) 131 (63.6) <0.001 cardiogenic 275 (46.8) 106 (63.1) 169 (40.3) 134 (45.7) 59 (67.8) 75 (36.4) time from arrest to chest compression < 15 min 476 (76.8) 139 (78.5) 337 (76.1) 0.513 240 (77.4) 73 (79.3) 167 (76.6) 0.598 ≥ 15 min 144 (23.2) 38 (21.5) 106 (23.9) 70 (22.6) 19 (20.7) 51 (23.4) cpr duration < 30 min 263 (42.4) 112 (63.3) 151 (34.1) <0.001 126 (40.6) 50 (54.3) 76 (34.9) 0.001 ≥ 30 min 357 (57.6) 65 (36.7) 292 (65.9) 184 (59.4) 42 (45.7) 142 (65.1) airway management ett 456 (73.5) 147 (83.1) 309 (69.7) 0.001 245 (79.0) 81 (88.0) 164 (75.2) 0.016 bvm 148 (23.9) 24 (13.6) 124 (28.0) 57 (18.4) 8 (8.7) 49 (22.5) lma 16 (2.6) 6 (3.4) 10 (2.3) 8 (2.6) 3 (3.3) 5 (2.3) defibrillation no 472 (76.1) 117 (66.1) 355 (80.1) <0.001 240 (77.4) 61 (66.3) 179 (82.1) 0.002 yes 148 (23.9) 60 (33.9) 88 (19.9) 70 (22.6) 31 (33.7) 39 (17.9) fluid resuscitation no 17 (2.7) 2 (1.1) 15 (3.4) 0.295 6 (1.9) 1 (1.1) 5 (2.3) 0.602 0.9% nacl 574 (92.6) 167 (94.4) 407 (91.9) 295 (95.2) 87 (94.6) 208 (95.4) lactate ringer 29 (4.7) 8 (4.5) 21 (4.7) 9 (2.9) 4 (4.3) 5 (2.3) medication during cpr adrenaline 618 (99.7) 177 (100.0) 441 (99.5) 1.000 310 (100.0) 92 (100.0) 218 (100.0) na 7.5% sb 247 (39.8) 62 (35.0) 185 (41.8) 0.122 128 (41.3) 36 (39.1) 92 (42.2) 0.616 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 6 table 1: characteristics of patients with out-of-hospital cardiac arrest with and without sustained return of spontaneous circulation (rosc) in derivation and validation sets characteristics derivation set (n = 620) p-value validation set (n = 310) p-value total sustained rosc death total sustained rosc death) (n = 620) (n = 177) (n = 443) (n = 310) (n= 218) (n = 92) amiodarone 56 (9.0) 17 (9.6) 39 (8.8) 0.753 27 (8.7) 6 (6.5) 21 (9.6) 0.375 50% glucose 49 (7.9) 8 (4.5) 41 (9.3) 0.048 29 (9.4) 9 (9.8) 20 (9.2) 0.867 10% cg 100 (16.1) 25 (14.1) 75 (16.9) 0.391 56 (18.1) 17 (18.5) 39 (17.9) 0.902 cbg median (iqr) 136.5 52.5–211124 22 –200 158 101–236 <0.001 129.5 24 –208 118 1 –198 153 95252 <0.001 pupil reflex non-response 598 (96.5) 162 (91.5) 436 (98.4) <0.001 298 (96.1) 84 (91.3) 214 (98.2) 0.008 response 22 (3.5) 15 (8.5) 7 (1.6) 12 (3.9) 8 (8.7) 4 (1.8) response time ≤ 8 min 162 (26.1) 57 (32.2) 105 (23.7) 0.030 81 (26.1) 25 (27.2) 56 (25.7) 0.786 > 8 min 458 (73.9) 120 (67.8) 338 (76.3) 229 (73.9) 67 (72.8) 162 (74.3) data are presented as mean ± standard deviation (sd); median (interquartile range;iqr), or frequency (%). abbreviations: bvm: bag valve mask; cpr: cardiopulmonary resuscitation; ett: endotracheal tube; lma: laryngeal mask airway; na, data not applicable; cbg: capillary blood glucose; sb: sodium bicarbonate; cg: calcium gluconate. p-value corresponds to t independent samples t-test, m mann–whitney u test, c chi-square test, or ffisher’s exact test. table 2: multivariate logistic regression analyses to identify the independent factors associated with a sustained return of spontaneous circulation at the scene factors b or 95% ci p-value score cpr duration < 30 min 1.620 5.05 (3.34–7.65) <0.001 3 ≥ 30 min 1.00 reference advanced airway management bag valve mask 1.00 reference endotracheal tube 1.119 3.06 (1.77–5.31) <0.001 2 laryngeal mask airway 1.230 3.42 (1.02–11.46) 0.046 2.5 defibrillation no 1.00 reference yes 0.717 2.05 (1.31–3.2) 0.002 1.5 capillary blood glucose (mg%) (1) 1.00 reference < 150 0.670 1.95 (1.05–3.65) 0.035 1 ≥ 150 1.056 2.87 (1.56–5.29) 0.001 2 pupil reflex no response 1.00 reference response 1.084 2.96 (1.1–7.96) 0.032 2 response time ≤ 8 min 0.506 1.66 (1.07–2.57) 0.023 1 > 8 min 1.00 reference data are presented with 95% confidence interval (ci). or: adjusted odds ratio estimated by multiple logistic regression; cpr: cardiopulmonary resuscitation. variables included in the multivariable model had p < 0.050 in the univariate analysis. model summary: –2 log likelihood = 623.963, cox & snell r square = 0.173, nagelkerke r square = 0.248. hosmer and lemeshow test: chi-square = 8.418, df = 8, p-value = 0.394. constant: –3.704. vious study in a province in central thailand, reporting an incidence of 39.0% for sustained rosc (7). the present study demonstrated that rosc achieved in thailand was higher than that in a low-income country with an incidence of only 27.35% for rosc in the emergency department (20). previous empirical evidence showed that countries with high economic and social status had a low incidence of ohca and significantly high rate of favorable outcomes for rosc (21)(22). second, six predictors were associated with a sustained rosc at the scene, including cpr duration < 30 min, advanced airthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e33 way management with endotracheal tube (ett) and laryngeal mask airway (lma), defibrillation, pupillary light reflex, and response time ≤ 8 min. the possible explanation regarding patients with ohca having cpr duration < 30 min, specified as the duration from the fmc to the end of cpr, was that patients with ohca having cpr duration < 30 min had a chance of sustained rosc, consistent with a nationwide multicenter observational study in japan reporting that patients with ohca receiving cpr < 30 min would have an increased chance of rosc at the scene and 1-month survival and favorable neurological outcome defined by cerebral performance category scores 1 or 2, compared with patients with ohca having cpr duration > 30 min. however, the authors explained that the outcomes were due to factors such as shockable rhythm, witnessed arrest, and bystander cpr (23) and comparable with those of a previous study finding that the most optimal cutoff for prehospital cpr duration in the non-traumatic group of patients with ohca for obtaining rosc and favorable neurological outcome at hospital discharge was 12 min, independent of cardiac rhythm. a longer cpr duration did not increase the rate of achieving rosc (24). therefore, cpr duration could help emergency medical personnel working prehospitally properly decide whether to terminate cpr in patients requiring prolonged cpr. the explanation regarding patients with ohca obtaining prehospital advanced airway management with ett and lma as factors that helped increase sustained rosc at the scene compared with bag valve masks (bvms) was consistent with our previous study from the national ems database of thailand, reporting that patients with ohca who received advanced airway management with ett had 3.88 times higher chance of rosc at the scene compared with those with bvms (10). additionally, they were similar to results of several studies reporting that prehospital advanced airway with ett and lma by paramedics in patients with ohca were associated with increased rate of rosc at the scene, compared with patients with ohca using bvms (25-27), which was in contrast to a previous study finding that airway management with ett during cpr in emergency department was associated with worsened outcome of rosc and decreased survival until discharge at 28 days, compared with the non-ett group with bvms (28), and ett and lma applications during cpr for patients with in-hospital cardiac arrest were associated with increase of no-flow interval, compared with bvms application. a high no-flow interval is associated with worsened neurological outcome, and helps emergency medical personnel in deciding for cpr initiation or termination in patients with ohca (29). ett insertion is the gold standard definitive airway management, but it has numerous limitations, such as local protocol; in some areas or countries, paramedics or emergency nurse practitioners (enps) are not allowed to insert ett, except when a physician is available and an ambulance is present at the scene. however, for the study area, paramedics and enps were allowed to insert ett and administer medication in patients with ohca under offline protocol (5). defibrillation was associated with a sustained rosc at the scene, which was similar to a previous systematic review and metaanalysis reporting that patients with ohca who received prehospital defibrillation had increased 1-month favorable neurological outcomes, and the rate was higher in patients presenting with initial shockable heart rhythms including ventricular fibrillation (vf) and pulseless ventricular tachycardia (vt) compared with patients without defibrillation and presenting with non-shockable rhythms (8). in this study, prehospital cbg was associated with a sustained rosc. even if hypoglycemia was one of the reversible causes of cardiac arrest in 2005 guidelines (30) and removed in acls 2010 (31), 2015 (32), and 2020 (33), recently the observational study in the emergency department in thailand found that patients with ohca who had intra-arrest blood glucose level < 100 mg/dl had decreased rate of sustained rosc (34), which was consistent with the results of a large study retrospectively collecting data of patients with in-hospital cardiac arrest for 10 years in taiwan. it reported that patients who had intra-arrest blood glucose level < 150 mg/dl had worse neurological outcomes and decreased rate of rosc (35). for the study area, prehospital cbg administration is routine practice in patients with ohca and in patients with hypoglycemia, which is easily corrected in the prehospital context by 50% glucose intravenous administration and normal blood glucose level was tried to be maintained during cpr. this was believed to help improve clinical outcomes. this study revealed that patients with ohca who had pupillary light reflex had more chances of sustained rosc than patients without pupillary light reflex. the finding was consistent with a previous study reporting that pupillary light reflex could be used to predict outcomes after cardiac arrest, especially increased rosc rate. in contrast, patients without pupillary light reflex would have significantly increased mortality rate (36), which contradicts the results of a recent study reporting that measurement of pupil size and pupillary light reflex could not be used to predict rosc and the measurements were not associated with neurological outcomes in patients with cardiac arrest (37). another factor used in the prediction of sustained rosc was response time ≤ 8 min, which was defined as the interval between emergency call to ambulance arrival at the scene. this result was consistent with those of previous studies reporting that response time was associated with a sustained rosc at the scene and neurological outcome, and with each minute increase in response time, the chance of rosc would decrease in patients with ohca (5, 15). in the study area, response time was guaranteed to be at most 8 min in patients identified with unthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index t. huabbangyang et al. 8 consciousness or cardiac arrest. in patients with cardiac arrest, staff at the dispatch center advised callers to perform dispatcher-assisted bystander cpr (da-cpr) before the ambulance arriving at the scene, and in the study area, the traffic police were coordinated to ensure the traffic route of ambulances and reduce response time. third, this study developed a simple tool for prediction of sustained rosc at the scene, helping prehospital emergency medical personnel, such as eps, paramedics, and enps, to identify predictors of sustained rosc in patients with ohca, and patients’ relatives could know the prognosis in emergency situations. factors that influence the management of patients with ohca at the scene could be used in the prediction of sustained rosc. this study developed a simple tool for the prediction of sustained rosc in patients with ohca, called prad-ccpr score, including six factors, namely, pupil reflex, response time, airway management, defibrillation, cbg, and cpr duration. the total score ranged from 0 to 15, with simplicity and convenience in remembrance and clinical application and appropriate to prehospital context. the score of at least 6 was the most suitable cutoff point in prediction of sustained rosc at the scene with auc of 0.759 (95% ci 0.715–0.802, p < 0.001), sensitivity of 62.0% (95% ci 51.2–71.9), specificity of 75.7% (95% ci 69.4–81.2), ppv of 51.8% (95% ci 40.9–62.3), and npv of 79.5% (95% ci 73.5–84.6). to the authors’ knowledge, so far, four scores have been developed for immediate prediction of rosc outcome, comprising watch-cpr score (including witnessed arrest, time from arrest to chest compression, and cpr duration) (7). watch-cpr score ≥2 could be used to predict a chance of sustained rosc in the emergency department. this study collected data in prehospital and ed settings. notwithstanding, the watch-cpr score would be easy to apply, and many important data were still believed to be missed in the context of management by the ems team in specific situations, for example, management of patients with ohca, such as response time and prehospital advanced airway management. the raca score had auc of 0.710 (95% ci 0.697–0.724) including factors such as sex, age ≥80 years, witnessed arrest, asystole, arrest location, presumable etiology of cardiac arrest, bystander cpr, and time until professional arrival (13). however, the raca score was difficult, complex, and inappropriate to apply in emergency conditions in the context of prehospital management. besides, the interpretation of the score was complex and unfit for application. the nullplease score variables included non-shockable rhythm, unwitnessed arrest, long no-flow period, long low flow period, ph < 7.2, lactate > 7, end-stage renal failure on dialysis, age > 85 years, on-going cpr, and extracardiac cause; and it had auc of 0.632 (95% ci 0.523–0.741) (14). the null-please score was thought to be suitable for the hospital context. however, since obtaining the results of some included parameters took time, and because no blood gas test and lactate test are available outside the hospital and in the context of prehospital ems in thailand, it could not be applied in this setting. the p-rosc score is made up of variables including age, time to ems arrival, first rhythm, arrest witnessed, and prehospital drug administration, and has an auc of 0.806 (95% ci 0.799 –0.814) (15). nevertheless, the p-rosc score only used prehospital parameters in the prediction of rosc in patients with ohca using only five parameters. the prosc score had a total score of 100, and the score proportion was divided for each parameter with complexity, inappropriate to apply in emergencies, and pressured conditions as the management of patients with ohca. therefore, the pradccpr score was proposed, which was a simple tool for the prediction of sustained rosc at the scene including practical parameters in the context of prehospital management, comprising treatment at the scene by an ems team, for assisting eps, paramedics, and enps when making critical decisions for patients with ohca regarding survival prediction. 5. limitations this study has several limitations. first, it was a retrospective observational study, collecting data in a single center, an advanced emergency medical operation unit in bangkok, thailand, a middle-income country. thus, due to differences between areas, the study results may not be indicative in other areas and it is required to assess the external validity of the score. second, this study only analyzed sustained rosc at the scene. additional studies are needed on the predictive performance of the score regarding long-term outcomes, such as survival to hospital discharge and neurological function outcome in patients with ohca. third, all data were retrospectively collected from the ems patient care report; although neutrality was tried to be maintained in every way possible, there might be a risk of selection bias. 6. conclusion in this study, a score called prad-ccpr was developed and validated for predicting sustained rosc in patients with ohca at the scene in a middle-income country. an optimal score of ≥ 6 provides an acceptable area under the roc curve of 0.759 with sensitivity and specificity of 62.0% and 75.7%, respectively. this predictive score might help cpr commanders to prognosticate the outcome of patients with ohca at the scene. 7. declarations 7.1. acknowledgments the authors are grateful to the navamindradhiraj university research fund for pub. we would like to thank the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e33 table 3: screening performance characteristics of the pradd-cpr model for predicting the sustained return of spontaneous circulation (rosc) after out of hospital cardiac arrest in different cutoff points score sensitivity specificity ppv npv lr+ lr(95% ci) (95% ci) (95% ci) (95% ci) (95% ci) (95% ci) 1.0 100(96.1–100) 1.8(0.5–4.6) 30.1(25–35.5) 100(39.8–100) 1.02(1–1.04) 0 2.0 100(96.1–100) 3.7(1.6–7.1) 30.5(25.3–36) 100(63.1–100) 1.04(1.01–1.07) 0 2.5 100(96.1–100) 4.1(1.9–7.7) 30.6(25.4–36.1) 100(66.4–100) 1.04(1.01–1.07) 0 3.0 100(96.1–100) 11.5(7.6–16.5) 32.3(26.9–38) 100(86.3–100) 1.13(1.08–1.18) 0 3.5 100(96.1–100) 12.4(8.3–17.5) 32.5(27.1–38.3) 100(87.2–100) 1.14(1.09–1.2) 0 4.0 90.2(82.2–95.4) 32.1(26–38.7) 35.9(29.7–42.5) 88.6(79.5–94.7) 1.33(1.19–1.49) 0.31(0.16–0.58) 4.5 89.1(80.9–94.7) 34.9(28.6–41.6) 36.6(30.3–43.3) 88.4(79.7–94.3) 1.37(1.21–1.54) 0.31(0.17–0.58) 5.0 73.9(63.7–82.5) 60.6(53.7–67.1) 44.2(36.2–52.4) 84.6(78–89.9) 1.87(1.53–2.3) 0.43(0.3–0.62) 5.5 69.6(59.1–78.7) 65.1(58.4–71.4) 45.7(37.3–54.3) 83.5(77.1–88.8) 2(1.59–2.5) 0.47(0.34–0.65) 6.0a 62.0(51.2–71.9) 75.7(69.4–81.2) 51.8(42.1–61.4) 82.5(76.5–87.5) 2.55(1.92–3.38) 0.5(0.38–0.66) 6.5 51.1(40.4–1.7) 79.8(73.9–84.9) 51.6(40.9–62.3) 79.5(73.5–84.6) 2.53(1.82–3.52) 0.61(0.49–0.76) 7.0 39.1(29.1–49.9) 85.3(79.9–9.7) 52.9(40.4–65.2) 76.9(71–82) 2.67(1.77–4.01) 0.71(0.6–0.85) 7.5 33.7(24.2–44.3) 87.6(82.5–91.7) 53.4(39.9–66.7) 75.8(70–80.9) 2.72(1.73–4.29) 0.76(0.65–0.88) 8.0 20.7(12.9–30.4) 95.4(91.7–97.8) 65.5(45.7–82.1) 74(68.5–79) 4.5(2.18–9.3) 0.83(0.75–0.93) 8.5 18.5(11.1–27.9) 96.8(93.5–98.7) 70.8(48.9–87.4) 73.8(68.3–78.8) 5.75(2.47–13.4) 0.84(0.76–0.93) 9.0 12(6.1–20.4) 99.1(96.7–99.9) 84.6(54.6–98.1) 72.7(67.3–77.7) 13(2.95–57.6) 0.89(0.82–0.96) 9.5 5.4(1.8–2.2) 99.5(97.5–100) 83.3(35.9–99.6) 71.4(65.9–76.4) 11.8(1.4–100) 0.95(0.9–1) 10.0 5.4(1.8–12.2) 99.5(97.5–100) 83.3(35.9–99.6) 71.4(65.9–76.4) 11.8(1.4–100) 0.95(0.9–1) data are presented with 95% confidence interval (ci). lr: likelihood ratio; npv: negative predictive value; ppv: positive predictive value. a the best threshold value was determined using youden’s index (youden index j = sensitivity + specificity – 1). paramedics at v-ems, faculty of medicine vajira hospital, navamindradhiraj university, for facilitating in data collection and access in the present study, gawin tiyawat, md., chief of department of disaster and emergency medical operation, faculty of science and health technology, navamindradhiraj university, and chunlanee sangketchon, md., deputy dean of faculty of science and health technology, navamindradhiraj university, for support and suggestions in the research development and aniwat berpan, md. for suggestions on english for the present study. 7.2. conflict of interest the authors have no conflicting interests to declare. 7.3. fundings and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution conceptualization: thongpitak huabbangyang, chaleamlap thongpean, wannakorn pralomcharoensuk, weerawan khaokaen and sunisa bumrongchai; methodology: thongpitak huabbangyang, chaleamlap thongpean, wannakorn pralomcharoensuk, weerawan khaokaen and sunisa bumrongchai; software: thongpitak huabbangyang; validation: thongpitak huabbangyang; agasak silakoon and pramote papukdee; formal analysis: thongpitak huabbangyang; investigation: thongpitak huabbangyang, ratree chaisorn and chomkamol saumok; resources: thongpitak huabbangyang, chaleamlap thongpean, wannakorn pralomcharoensuk, weerawan khaokaen and sunisa bumrongchai; data curation: thongpitak huabbangyang; writing – original draft: thongpitak huabbangyang; writing review & editing: thongpitak huabbangyang, agasak silakoon and pramote papukdee; visualization: thongpitak huabbangyang and rossakorn klaiangthong; supervision: thongpitak huabbangyang; project administration: thongpitak huabbangyang; funding acquisition: thongpitak huabbangyang. all authors read and approved the final version of manuscript. 7.5. data availability the datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. references 1. gräsner j-t, lefering 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m-s, chou e, yu p-h, et al. associations between intra-arrest blood glucose level and outcomes of adult in-hospital cardiac arrest: a 10-year retrospective cohort study. resuscitation. 2020;146:103-10. 36. peluso l, oddo m, sandroni c, citerio g, taccone fs. early neurological pupil index to predict outcome after cardiac arrest. intensive care med. 2022;48(4):496-7. 37. riker rr, sawyer me, fischman vg, may t, lord c, eldridge a, et al. neurological pupil index and pupillary light reflex by pupillometry predict outcome early after cardiac arrest. neurocrit care. 2020;32:152-61. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 99 emergency (2015); 3 (3): 99-102 original research comparison of the analgesic effect of intravenous acetaminophen and morphine sulfate in rib fracture; a randomized double-blind clinical trial mehrdad esmailian, roshanak moshiri*, majid zamani department of emergency medicine, al-zahra hospital, isfahan university of medical sciences, isfahan, iran. *corresponding author: roshanak moshiri; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989136470851; fax: +983117923445; email: roshanak_moshiri86@yahoo.com received: october 2014; accepted: december 2014 abstract introduction: rib fracture is one of the common causes of trauma disabilities in many events and the outcome of these patients are very extensive from temporary pain management to long-term significant disability. control and management of the pain in such patients is one of the most important challenges in emergency departments. thus, the aim of the present study was assessing the efficacy of iv acetaminophen in pain control of patients with rib fracture. methods: in this double-blind clinical trial, 54 patients over 18 years of age, referred to two educational hospitals with rib fracture, were entered. patients were randomly categorized in two groups of morphine sulfate (0.1 milligram per kilogram of body weight) and iv acetaminophen (1gram), as single-dose infused in 100 cc normal saline. the pain severity was measured by numeric rating scale (nrs) on arrival and 30 minutes after drug administration. at least three scores reduction was reported as therapeutic success. results: the mean and standard deviation of patients’ age was 41.2 ± 14.1 years. there is no difference in gender (p=0.24) and age frequency (p=0.77) between groups. 30 minutes after drug administration the mean of pain severity were 5.5 ± 2.3 and 4.9 ± 1.7 in morphine and acetaminophen groups, respectively (p=0.23). success rate in morphine and acetaminophen groups were 58.6% (95% cl: 39.6-77.7) and 80% (95% cl: 63.2-96.7), respectively, (p=0.09). only 3 (5.6%) patients had dizziness (p=0.44) and other effects were not seen in any of patients. conclusion: the findings of the present study shows that intravenous acetaminophen and morphine have the same therapeutic value in relieving the pain of rib fracture. the success rate after 30 minutes drug administration were 80% and 58.6% in acetaminophen and morphine groups, respectively. presentation of side effects was similar in both groups. key words: acetaminophen; morphine; pain management; rib fractures cite this article as: esmailian m, moshiri r, zamani m. comparison of the analgesic effect of intravenous acetaminophen and morphine sulfate in rib fracture; a randomized double-blind clinical trial. emergency. 2015;3(3):99-102 introduction: ib fracture is one of the common causes of trauma disabilities in many events such as traffic accidents, falling, occupational events, and intentional traumas (1-4). the outcome of these patients are very extensive from temporary pain management to long-term significant disability (1, 5, 6). recent studies showed that prolonged pain in the chest wall of patients with rib fracture is more prevalent than previously thought, so that about 60% of them suffer from longterm pain and disability (1, 7). patients with rib fracture have severe pain during breathing, speaking, coughing, and even body movements (3, 8). thus, rapid pain control has high priority to reduce the risk of pulmonary and systemic effects derived from the fracture such as decrease the respiratory effort which leads to hypoxia, atelectasis, and even pneumonia (9). the presence guidelines recommend using opioids for these patients, but tolerance, probability of breathing depression, and other side effects of these products limit their use. consequently, the recent studies have searched to find alternative or auxiliary treatments for decreasing such side effects. intravenous (iv) acetaminophen, given the food and drug administration confirmation in 2010 to management of mild to moderate pains, is introduced as an auxiliary drug to treatment of moderate to severe pains. although acetaminophen causes to relieve the pain significantly and improving opioid sparing effects, it does not reduce the adverse effects arise from opioids such as vomiting and nausea (10). however, recent researches have declared that with considering economical and clinical evidences, administration of iv acetaminophen r this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com esmailian et al 100 should not be replaced by rectal or oral form unless for the patient cannot take it through these ways. but, rapid pain relief in trauma patients is an indication for iv administration based on which new protocols have been presented to introduce it as the first-line therapy in patients with rib fracture (9). another indication of this drug is the patients who cannot tolerate non-opioid analgesic or antipyretic drugs (11). since the pain is a main obstacle to examination, diagnosis, and treatment, control and management of the pain in trauma patients, especially in those with rib fracture, is one of the most important challenges in emergency departments (12, 13). in all studies, non-opioid analgesic drugs are presented as a therapeutic indication in trauma cases and their iv form such as acetaminophen is more considered by physicians in critical conditions (9). nevertheless, these findings have not yet been published to show their therapeutic value. thus, the aim of the present study was assessing the efficacy of iv acetaminophen in pain control of patients with rib fracture. methods: study design and setting in this double-blind study, 54 patients over 18 years of age, referred to two educational hospitals with rib fracture, were entered and randomly categorized in two groups. the protocol of the study was confirmed by ethical committee of esfahan university of medical sciences and consent form given from patients. during the study, all researchers observed the declaration of helsinki. the study was registered in iranian registry of clinical trial (irct number: irct2015042812072n2). inclusion criteria were presence one or two rib fractures confirmed by chest radiography, normal level of consciousness (glasgow coma scale of 15), weight range between 60100 kg, and pain score>4 centimeters based on numeric rating scale (14). excluded criteria were dissatisfaction toward participation, background pulmonary problems, history of taking analgesic or opioid drugs, addiction, history of liver or kidney diseases, head trauma, pregnancy, history of taking monoamine oxidase, hypnotic and sedative drugs, as well as phenobarbital and isoniazid, respiratory arrest on arrival and repeated vomiting and nausea. patients was sequentially entered to the study and randomization was done using computer generated sets of random allocations by a physician who did not involve in data gathering. all emergency staff included physicians, nurses, and researches were blind to the study. to ensure from blindness status, drugs were prepared as clear solutions in dark packs and only the person prepared them was aware from their content. drug packs were coded and delivered to the drug prescribers. for doing the study as double blind, preparation and injection of solutions as well as record of results were separately performed by three physicians who did not in touch with each other during the study. information regarding iv drugs was accessible to therapeutic staff only when side effects or other clinical changes happened to the patient. patients were randomly categorized in two groups of morphine sulfate (0.1 milligram per kilogram of body weight, single-dose, and infused in 100 cc normal saline) and iv acetaminophen (1gram, single-dose, and infused in 100 cc normal saline). if the pain was not relieved after the first 30 minutes, a rescue dose of morphine was injected by a trained physician, drugdemographic data of studied patients based on administered table 1: variables morphine acetaminophen p age (mean ± sd) 41.3 ± 14.1 41.0 ± 14.3 0.77* weight (kilogram) 65.4 ± 2.9 64.9 ± 3.0 0.76* gender female 10 (34.5) 5 (20.0) male 19 (65.5) 20 (80.0) 0.24 reason of fracture road traffic injury 21 (72.4) 12 (48.0) 0.25# falling <5 meters 5 (17.2) 8 (32.0) falling >5 meters 0 (0.0) 1 (4.0) direct trauma 3 (10.3) 4 (16.0) fracture frequency one 20 (71.4) 15 (60.0) 0.38* two 8 (28.6) 10 (40.0) co-injury no 25 (89.3) 25 (100.0) 0.49# pneumothorax 2 (7.1) 0 (0.0) hemothorax 1 (3.6) 0 (0.0) baseline pain severity (mean ± sd) 8.6 ±1.6 9.2 ± 1.3 0.19 *, based on mann-whitney u test; #, based on fisher's exact test; sd: standard deviation; pain severity measured by numeric rating scale. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 101 emergency (2015); 3 (3): 99-102 considered as a treatment failure. the patient was continuously monitored and vital signs (body temperature, blood pressure, respiratory rate, and pulse rate), level of arterial oxygen saturation, and drug side effects were recorded. the pain severity was measured by numeric rating scale on arrival and 30 minutes after drug administration. in addition, adverse effects of drugs including vomiting and nausea, respiratory depression (respiratory rate less than 10 times per minute) and dizziness were evaluated. the primary outcome was defined as decreasing the pain severity that at least three scores reduction was reported as therapeutic success. presentation of side effects was also considered as secondary outcome. with considering 95% confidence interval (α=0.05), 80% power (β=0.2), and 1.65 standard deviation, with 1.3 centimeters reduction in pain severity because of drug efficacy (d=1.3), the sample volume was calculated 25 subjects in each group (15). statistical analysis data was analyzed using spss 11.0 version. pain severity was showed as mean and standard deviation as well as successful rate as frequency and percentage. mannwhitney u test was applied for assessing the difference of quantitative and rating factors, while chi-square and fisher’s exact tests for qualitative and numerical ones. p<0.05 was statistically significant. results: 54 patients were entered, 29 cases in morphine group and 25 ones in acetaminophen, 39 (72.2%) cases was male. the mean and standard deviation of patients’ age was 41.2 ± 14.1 years. there is no difference in gender (p=0.24) and age frequency (p=0.77) between groups. table 1 shows demographic data of the studied patients. figure 1: the success rate of morphine and acetaminophen in reducing the pain of fractures. data is shown as percentage with 95% confidence interval. the mean of pain severity on arrival were 8.6 ± 1.6 and 9.2 ± 1.3 in morphine and acetaminophen groups (p=0.19), respectively. 30 minutes after drug administration this mean were 5.5 ± 2.3 and 4.9 ± 1.7 in morphine and acetaminophen groups, respectively (p=0.23). success rate in morphine and acetaminophen groups were 58.6% (95% cl: 39.6-77.7) and 80% (95% cl: 63.296.7), respectively, (p=0.09) (figure 1). only 3 (5.6%) patients had dizziness, 1 (3.5%) case in morphine group and 2 (8%) ones in acetaminophen (p=0.44). other effects were not seen in any of patients. discussion: the findings of the present study showed that iv acetaminophen and morphine have the same therapeutic value in relieving the pain of rib fracture. the pain of rib fracture may lead to exacerbate the lung injuries in chest trauma. thus, administration of an analgesic and sedative drug has priority for these patients to improving the breathing, cough reflex, and respiratory physiotherapy (16). a review article in 2003 showed that presentation of a safe and effected method as a standard tool to decrease the pain of rib fracture is complicated. therefore, having enough knowledge regarding strong and weak points of each drug is essential for physician to choose the appropriate medication according to clinical conditions and patient’s status (17). only one protocol in 2014 was published that considered the role of iv acetaminophen in pain management of rib fracture (fracture in three ribs or more). this protocol, which was written based on the experiences of a therapeutic center, showed that iv acetaminophen is the first-line therapy in such patients (9). similar to this guideline, the present study declared that using iv acetaminophen as singledose can be an appropriate medication for patients with rib fracture. the success rate reported for this drug in this study was 80% that although did not have significant difference with morphine (58.6%), it had more improvement rate, clinically. even with supposing the same rate of success between the two drugs, using iv acetaminophen because of clinical (lesser side effects and contraindications) and economical (being cheaper) aspects are more rational. also, in tsang et al. study, it was declared that administration of iv acetaminophen with morphine causes to decrease the dose of morphine significantly, while both treatment protocols (acetaminophen with morphine and morphine alone) have the same efficacy in reducing the pain (18). moreover, zare et al. showed that administration of iv acetaminophen and oral oxycodone have more efficacy than morphine in pain management, but they have more side effects in compare to morphine (19). finally, no difference was seen between side effects of drugs in two groups, representative the safety of acetaminophen in relieving the pain of rib fracture. paydar and colleagues also stated that during one year using iv acetaminophen in patients 58.6 80.0 0 20 40 60 80 100 120 morphine acetaminophen s u c c e s s r a te ( % ) treatment this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com esmailian et al 102 with rib fracture, no cases of hypotension, respiratory depression, loss of consciousness, and etc. was observed (9). small sample size was the limitation of this study; if the number of patients was more, maybe the difference between success rate of acetaminophen and morphine would be significant in pain relieving of rib fracture. in addition, lacking of placebo was considered as another limitation of the present project, which because of ethical issues there was no possible to cancel the medication. conclusion: the findings of the present study shows that iv acetaminophen and morphine have the same therapeutic value in relieving the pain of rib fracture. the success rate after 30 minutes drug administration were 80% and 58.6% in acetaminophen and morphine groups, respectively. presentation of side effects was similar in both groups. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of al-zahra hospitals, isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors met four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. fabricant l, ham b, mullins r, mayberry j. prolonged pain and disability are common after rib fractures. am j surg. 2013;205(5):511-6. 2. brasel kj, guse ce, layde p, weigelt ja. rib fractures: relationship with pneumonia and mortality. crit care med. 2006;34(6):1642-6. 3. gordy s, fabricant l, ham b, mullins r, mayberry j. the contribution of rib fractures to chronic pain and disability. am j surg. 2014;207(5):659-63. 4. alimohammadi h, baratloo a, abdalvand a, rouhipour a, safari s. effects of pain relief on arterial blood o2 saturation. trauma monthly. 2014;19(1). 5. lotfipour s, kaku sk, vaca fe, et al. factors associated with complications in older adults with isolated blunt chest trauma. west j emerg med. 2009;10(2):79-84. 6. safari s, baratloo a, negida as, taheri ms, hashemi b, selkisari sh. comparing the interpretation of traumatic chest x-ray by emergency medicine specialists and radiologists. archives of trauma research. 2014;3(4). 7. forouzanfar mm, safari s, niazazari m, et al. clinical decision rule to prevent unnecessary chest x-ray in patients with blunt multiple traumas. emergency medicine australasia. 2014;26(6):561-6. 8. marasco s, lee g, summerhayes r, fitzgerald m, bailey m. quality of life after major trauma with multiple rib fractures. injury. 2014;46(1):61-5. 9. paydar s, farhadi p, ghaffarpasand f, et al. acute trauma pain control algorithm. bull emerg trauma. 2014;2(4):170-1. 10. pasero c, stannard d. the role of intravenous acetaminophen in acute pain management: a case-illustrated review. pain manag nurs. 2012;13(2):107-24. 11. yeh yc, reddy p. clinical and economic evidence for intravenous acetaminophen. pharmacotherapy. 2012;32(6):559-79. 12. wattana mk, nelson ls, todd kh. prescription opioid guidelines and the emergency department. j pain palliat care pharmacother. 2013;27(2):155-62. 13. khan ms, shuaib w, evans dd, et al. evidence-based practice: best imaging practice in musculoskeletal disorders. j trauma nurs. 2014;21(4):170-9. 14. farrar jt, young jr jp, lamoreaux l, werth jl, poole rm. clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. pain. 2001;94(2):149-58. 15. todd kh, funk kg, funk jp, bonacci r. clinical significance of reported changes in pain severity. ann emerg med. 1996;27(4):485-9. 16. merritt ck, salinas oj, kaye ad. pain control in acute trauma. anesthesia for trauma: springer; 2014. p. 107-30. 17. karmakar mk, ho am-h. acute pain management of patients with multiple fractured ribs. j trauma. 2003;54(3):615-25. 18. tsang ks, page j, mackenney p. can intravenous paracetamol reduce opioid use in preoperative hip fracture patients? orthopedics. 2013;36(2 suppl):20-4. 19. zare ma, ghalyaie ah, fathi m, farsi d, abbasi s, hafezimoghadam p. oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate in acute bone fracture pain control: a double-blind placebo-controlled randomized clinical trial. eur j orthop surg traumatol. 2014;24(7):1305-9. emergency 2016; 4 (2): 65-71 or i g i n a l re s e a rc h ventilator weaning and spontaneous breathing trials; an educational review hossam zein1, alireza baratloo2, ahmed negida1∗, saeed safari2 1. faculty of medicine, zagazig university, zagazig, egypt. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: february 2016; accepted: march 2016 abstract: the term "weaning" is used to describe the gradual process of decreasing ventilator support. it is estimated that 40% of the duration of mechanical ventilation is dedicated to the process of weaning. spontaneous breathing trial (sbt) assesses the patient’s ability to breathe while receiving minimal or no ventilator support. the collective task force in 2001 stated that the process of sbt and weaning should start by assessing whether the underlying cause of respiratory failure has been resolved or not. weaning predictors are parameters that are intended to help clinicians predict whether weaning attempts will be successful or not. although the international consensus conference in 2005 did not recommend their routine use for clinical decision making, researchers did not stop working in this area. in the present article, we review some of the recent studies about weaning predictors, criteria, procedure, as well as assessment for extubation a mechanically ventilated patient. keywords: ventilator weaning; mechanical ventilation; emergency service, hospital; airway extubation; ventilator induced lung injury © copyright (2015) shahid beheshti university of medical sciences cite this article as: zein h, baratloo a, negida a, safari s. ventilator weaning and spontaneous breathing trials; an educational review. emergency. 2016; 4 (2): 65-71. 1. introduction t he term "weaning" is used to describe the gradual process of decreasing ventilator support. it is estimated that 40% of the duration of mechanical ventilation is dedicated to the process of weaning (1). delayed weaning can lead to complications such as ventilator induced lung injury (vili), ventilator associated pneumonia (vap), and ventilator induced diaphragmatic dysfunction (2-4). on the other hand, premature weaning can lead to complications like loss of the airway, defective gas exchange, aspiration and respiratory muscle fatigue (5-7). spontaneous breathing trial (sbt) assesses the patient’s ability to breathe while receiving minimal or no ventilator support. the collective task force in 2001 stated that the process of sbt and weaning should start by assessing whether the underlying cause of respiratory failure has been resolved or not (2). there is no consensus about what criteria should be used to assess reversal of the ∗corresponding author: ahmed negida; faculty of medicine, zagazig university, zagazig, el-sharkia, egypt. email: ahmed01251@medicine.zu.edu. eg ; postal code: 44519; tel: +201125549087 underlying condition. a combination of subjective and objective criteria is usually used to determine disease reversal. usually the criteria used are improvement of gas exchange, improvement of mental status, neuromuscular functional assessment and radiographic signs (7). however, it should be kept in mind that some patients who don’t meet these criteria are eventually successfully weaned (8). weaning predictors are parameters that are intended to help clinicians predict whether weaning attempts will be successful or not. although the international consensus conference in 2005 did not recommend their routine use for clinical decision making, researchers did not stop working in this area (9). in the present article, we review some of the recent studies about weaning predictors, criteria, procedure, as well as assessment for extubation a mechanically ventilated patient. 2. weaning predictors 2.1. heart rate variability the process of weaning leads to changes in the hemodynamic and autonomic nervous systems. two prospective observational studies showed that reduced heart rate variability this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com ahmed01251@medicine.zu.edu.eg ahmed01251@medicine.zu.edu.eg h. zein et al. 66 during spontaneous breathing trials (sbt) was significantly associated with extubation failure (10-12). acrentales et al. found that spectral coherence between heart rate variability and respiratory flow signals could predict extubation failure with good sensitivity and specificity (13). however, all these results still need validation in larger groups of patients. 2.2. sleep quality poor quality of sleep may affect the function of the respiratory muscles and weaning outcome. in a cross sectional study, chen et al. assessed the quality of sleep using the verran and snyder-halpern sleep scale and found that poor quality of sleep was significantly associated with weaning failure (14). 2.3. hand grip strength muscle weakness can negatively affect the weaning outcome (15). cottereau et al. assessed handgrip strength by a handheld dynamometer and found that handgrip strength was significantly associated with difficult or prolonged weaning but not with extubation failure (16). 2.4. diaphragmatic dysfunction the acquired diaphragmatic dysfunction following prolonged mechanical ventilation can affect the weaning outcome (17). dinino et al. assessed diaphragmatic dysfunction by measuring the difference between diaphragm thickness at the end of inspiration and expiration using ultrasonography to view the diaphragm in the zone of apposition. they found that a difference of 30% or more could predict extubation failure with a sensitivity of 88% and a specificity of 71% (18). 2.5. oxidative stress markers oxidative stress is a key mechanism involved in ventilator induced respiratory muscle dysfunction. verona et al. estimated the plasma levels of oxidative stress markers before and after sbt. they found higher plasma concentration of malondialdehyde and vitamin c, and lower level of nitric oxide in plasma were significantly associated with sbt failure (19). 3. weaning criteria table 1 shows some of derivate criteria of readiness for weaning trial (20, 21). according to the international consensus conference recommendations in 2005, these criteria should be thought of as considerations rather than as rigid thresholds that patients must meet all of them to be successfully weaned. because many patients were successfully discontinued from the ventilator although they didn’t meet one or more of them (9). table 1: criteria of readiness for weaning trial criteria subjective assessment adequate cough no neuromuscular blocking agents absence of excessive trachea-bronchial secretion reversal of the underlying cause for respiratory failure no continuous sedation infusion or adequate mentation on sedation objective measurements stable cardiovascular status heart rate ≤ 140 beat/minute no active myocardial ischemia adequate hemoglobin level ( ≥ 8 g/dl) systolic blood pressure 90–160 mmhg afebrile (36◦ c < temperature < 38◦ c) no or minimal vasopressor or inotrope (< 5 µg/kg/minute dopamine or dobutamine) adequate oxygenation tidal volume > 5 ml/kg vital capacity >10 ml/kg proper inspiratory effort respiratory rate ≤ 35/minute pao2 ≥ 60 and paco2 ≤ 60 mmhg positive end expiratory pressure ≤ 8 cmh2 o no significant respiratory acidosis (ph ≥ 7.30) maximal inspiratory pressure (mip) ≤ -20 – -25 cmh2 o o2 saturation > 90% on fio2 ≤ 0.4 (or pao2 /fio2 ≥ 200) rapid shallow breathing index (respiratory frequency/tidal volume) < 105 4. weaning procedure 4.1. planning step1: a weaning plan starts with assessing the ability of the patient for spontaneous breathing. three main strategies are used by clinicians to perform sbt. sbt strategies * t-piece trial, in which only supplemental oxygen is supplied through a t-piece connected to an endotracheal tube. * continuous positive airway pressure (cpap) trial using a cpap level equal to the previous positive end-expiratory pressure (peep) level. * invasive ventilation with low level of pressure support (5-8 cmh2o) or automatic tube compensation. there is no current evidence suggesting that one of these approaches is superior to the others (22, 23). a recent cochrane systematic review concluded that there is no difference between t-piece trials and pressure support trials regarding extubation failure and mortality with low quality of evidence. however, pressure support was found to be superior to t-piece in the proportion of successful sbt in patients considered to have simple weaning with moderate quality of evidence (relative risk 1.09; 95%ci: 1.02-1.17) (24). neil r macintyre suggested this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 67 emergency 2016; 4 (2): 65-71 that the t-piece approach may be considered if there is borderline performance with other techniques or there are concerns that loss of peep would precipitate latent cardiac dysfunction or lung failure (7). sbt duration based on strong evidence, the collective task force in 2001 recommended that the duration of sbt should be at least 30 minutes and not longer than 120 minutes (2). this means that physicians should wait at least 30 minutes to judge tolerance of the sbt, but they shouldn’t wait longer than 120 minutes if tolerance of the sbt is not clear (7). the initial few minutes of the sbt should be monitored closely before judgment is made to continue the sbt. there are some evidence regarding the harmful effects of respiratory muscle fatigue, if they occur early in failing sbts (7, 25-27). criteria of successful sbt table 2 illustrates the criteria used by clinicians to judge tolerance of sbts (20). according to neil r macintyre, these criteria should be interpreted in the context of each other and as changes from baseline, not as rigid thresholds (7). definition of weaning outcome based on sbt the international consensus conference in 2005 suggested a new classification of weaning outcomes (table 3). this classification has been shown in multiple observational studies to have prognostic value. some studies showed that only the prolonged weaning group significantly had higher mortality and longer hospital stay compared to the other two groups (28-31). jeong et al. concluded that ventilator free days, extubation failure, tracheostomy, and mortalities increased significantly across groups (32). funk et al. also concluded that ventilator free days and intensive care unit (icu) free days increased significantly in the difficult and prolonged classes (31). step 2 : if sbt was successful, step 2 would be assessment for airway removal. but, if sbt was unsuccessful, the collective task force in 2001 (2) recommended the following processes as step 2: * searching for an underlying cause of respiratory failure and table 2: criteria of successful spontaneous breathing trials respiratory rate < 35 breaths/minute good tolerance to spontaneous breathing trials heart rate < 140 /minute or heart rate variability of >20% arterial oxygen saturation >90% or pao2 > 60 mmhg on fio2 <0.4 80 < systolic blood pressure < 180 mmhg or <20% change from baseline no signs of increased work of breathing or distress * * accessory muscle use, paradoxical or asynchronous rib cageabdominal movements, intercostal retractions, nasal flaring, profuse diaphoresis, agitation. correcting it if possible. * using a comfortable non-fatiguing form of respiratory support. neil r macintyre showed that this support should be interactive and well synchronized with the patient effort (33). * screen every 24 hours for readiness for another sbt. 4.2. options protocolized versus non-protocolized weaning weaning protocols usually consist of 3 parts: 1) objective criteria to judge readiness to wean; 2) guidelines to decrease support gradually; and 3) criteria to assess readiness for extubation (34). the latest cochrane systematic review showed that the use of protocols led to shorter total duration of mechanical ventilation and no extra side effects with moderate quality of evidence. it also showed that protocols led to shorter duration of weaning and icu length of stay with low quality of evidence. there were considerable variations in the types of protocols used, types of patients and usual practices in icus, therefore the reviewers could not recommend a certain protocol for general use (35). automated versus non automated weaning automated systems use closed loop circuits to automatically adjust the level of support given to the patient. the latest cochrane systematic review showed that automated systems were associated with shorter duration of weaning (36). however there was substantial heterogeneity in the result (87%). it also showed that automated systems led to shorter duration of mechanical ventilation, length of icu stay with moderate heterogeneity. it did not show the automated systems to be beneficial in reducing the length of hospital stay, mortality rates, or need for re-intubation. compared to usual protocolized systems, automated systems showed shorter duration of weaning and shorter total duration of mechanical ventilation. 4.3. sedation optimization strategies excessive sedation can result in poor performance in sbts and prolong the duration of mechanical ventilation (7). the table 3: classification of weaning outcomes outcome definitions simple successful sbt after the first attempt difficult failed sbt at first attempt and required up to three trials or required <7days to reach successful sbt prolonged required >7days to reach successful sbt profuse diaphoresis, agitation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. zein et al. 68 most important sedation strategies are aiming at reducing the duration of mechanical ventilation and daily sedation interruption. atiken et al. investigated the benefits of protocolized sedation versus non-protocolized sedation in a cochrane systematic review including 633 patients and found that protocolized sedation did not result in a reduction in the duration of mechanical ventilation, icu length of stay, hospital length of stay or mortality rates. however they graded the quality of evidence as low due to the conflicting results from the two included studies (37). another cochrane systematic review investigated the benefits of daily sedation interruption versus no interruption. it found that there is no strong evidence that daily sedation interruption reduced the duration of mechanical ventilation, length of hospital or icu stay or mortality. in a subgroup analysis of studies performed in north america, they found that daily sedation interruption reduced the total duration of mechanical ventilation. however, the authors advised that the study results should be used cautiously as the studies were heterogeneous in the patients and methods (38). these results show that further well-reported randomized clinical trials with large number of patients and uniform interventions are needed to judge the usefulness of these strategies. 5. assessment for extubation after successful sbt, the patient should undergo assessment for removal of the airway. assessment includes factors leading to extubation failure. extubation failure is defined as reintubation within 48 hours of extubation. re-intubation is associated with prolonged hospital and icu stay and more tracheostomies (39). re-intubation rate is commonly used as an indicator of the aggressiveness of weaning behavior in icu units. it equals number of re-intubated patients divided by total number of extubated patients. a value too high suggests that weaning is done too early, and a value too low suggests unnecessary conservative practices. neil r macintyre suggested that a value of 5-20% is generally accepted (7). however, no significant differences were found between the ranges of 7-15% and <7%. table 4 shows factors leading to extubation failure(34). stridor at extubation stridor at extubation occurs due to narrowing of the upper airways. cuff leak test has been introduced as a predictor of stridor after extubation (40). the amount of air leaking through the airway after deflating the cuff of the endotracheal tube is measured. the average of three values of 6 consecutive breaths during continuous mandatory ventilation 24 hours before extubation is taken. a value of <110 ml is considered to identify patients at high risk for stridor after extubation (41). however, it should be kept in mind that low values may be due to crusts of secretions around the tube (7). table 4: risk factors of extubation failure failure of two or more consecutive spontaneous breathing trials chronic heart failure partial pressure of arterial carbon dioxide > 45 mmhg after extubation more than one coexisting condition other than heart failure weak cough upper-airway stridor at extubation age ≥ 65 years apache ii score >12 on the day of extubation patients in medical, pediatric or multispecialty icu* pneumonia as a cause of respiratory failure * intensive care unit. steroids and/or epinephrine can treat post extubation stridor. it is also possible to give steroids and/or epinephrine 24 hours before extubation for patients with low cuff leak values (42). airway protection capacity the ability of the patient to protect his airway from excessive secretions by effective cough is evaluated. this includes noting the quality of cough with airway suctioning, the amount of secretions and the frequency of suctioning (4, 43, 44). patients judged to be not capable of protecting their airway effectively should not be extubated (45). mental status it is controversial whether patients should have intact cognitive functions before extubation. a literature review showed that a glasgow coma score > 8 was associated with successful extubation, if airway protection capacity is adequate (46). the role of non-invasive ventilation (niv ) agarwal et al. conducted a meta-analysis of rcts comparing niv with standard medical therapy in extubation failure (47). it showed that niv when used prophylactically in patients with high risk for extubation failure was associated with lower risk for re-intubation and icu mortality. however, when patients already developed respiratory distress, niv didn’t show the same benefits. the role of high flow nasal cannula (hfnc) modern hfnc devices provide gas flow with a high rate up to 70 litter/minutr and thus can provide oxygen with a high fio2 up to 100%. maggiore et al. conducted an rct of hfnc versus conventional venture mask for oxygen delivery after extubation and found that hfnc was associated with better oxygenation and lower re-intubation rate (48). bortfain et al. found that hfnc was associated with better oxygenation, more ventilator free days and lower re-intubation rate (49). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 69 emergency 2016; 4 (2): 65-71 6. appendix 6.1. acknowledgements we would like to express our special thanks to faculty members of emergency department in shahid beheshti university of medical sciences. 6.2. author’s contributions all the authors have contributed to drafting/revising the manuscript, study concept, or design, as well as data interpretation. 6.3. conflict of interest all authors declare that there is no conflict of interest in this study. 6.4. funding/ support all authors declare that this study was accomplished without any funding or support and the authors were responsible for all expenses. this study was conducted without any sponsors. references 1. esteban a, ferguson nd, meade mo, frutos-vivar f, apezteguia c, brochard l, et al. evolution of mechanical ventilation in response to clinical research. american journal of 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creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction weaning predictors weaning criteria weaning procedure assessment for extubation appendix references archives of academic emergency medicine. 2023; 11(1): e45 rev i ew art i c l e the value of coronary artery disease – reporting and data system (cad-rads) in outcome prediction of cad patients; a systematic review and meta-analysis koohyar ahmadzadeh1 a , shayan roshdi dizaji1 a , mohammad kiah1, mohamad rashid2, reza miri3∗, mahmoud yousefifard1,3 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. student research committee, babol university of medical sciences, babol, iran. 3. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. received: march 2023; accepted: april 2023; published online: 15 june 2023 abstract: introduction: coronary computed tomographic angiography (ccta) reporting has traditionally been operatordependent, and no precise classification is broadly used for reporting coronary artery disease (cad) severity. the coronary artery disease reporting and data systems (cad-rads) was introduced to address the inconsistent ccta reports. this systematic review with meta-analysis aimed to comprehensively appraise all available studies and draw conclusions on the prognostic value of the cad-rads classification system in cad patients. methods: online databases of pubmed, embase, scopus, and web of science were searched until september 19th, 2022, for studies on the value of cad-rads categorization for outcome prediction of cad patients. results: 16 articles were included in this systematic review, 14 of which had assessed the value of cad-rads in the prediction of major adverse cardiovascular events (mace) and 3 articles investigated the outcome of all-cause mortality. our analysis demonstrated that all original cadrads categories can be a predictor of mace [hazard ratios (hr) ranged from 3.39 to 8.63] and all categories, except cad-rads 1, can be a predictor of all-cause mortality (hrs ranged from 1.50 to 3.09). moreover, higher cad-rads categories were associated with an increased hazard ratio for unfavorable outcomes among cad patients (p for mace = 0.007 and p for all-cause mortality = 0.018). conclusion: the evidence demonstrated that the cad-rads classification system can be used to predict incidence of mace and all-cause mortality. this indicates that the implementation of cad-rads into clinical practice, besides enhancing the communication between physicians and improving patient care, can also guide physicians in risk assessment of the patients and predicting their prognosis. keywords: coronary artery disease; risk assessment; cad-rads; reporting and data system cite this article as: ahmadzadeh k, roshdi dizaji s, kiah m, rashid m, miri r, yousefifard m. the value of coronary artery disease – reporting and data system (cad-rads) in outcome prediction of cad patients; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e45. https://doi.org/10.22037/aaem.v11i1.1997. 1. introduction coronary computed tomographic angiography (ccta) is an accurate and non-invasive tool with a high negative predictive value, which is increasingly being used for the evalua∗corresponding author: reza miri: prevention of cardiovascular disease research center, imam hossein hospital, madani avenue, tehran, iran. phone/fax: +982177582721; email: dr.rezamiri1@gmail.com, orcid: https://orcid.org/0000-0002-8568-9948. † corresponding author: mahmoud yousefifard: physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; email: yousefifard20@gmail.com / yousefifard.m@iums.ac.ir, orcid: https://orcid.org/0000-0001-5181-4985. a: first and second authors have had equal contributions. tion of patients with stable angina and acute coronary artery disease (cad) (1). ccta provides physicians with utile information on the presence of atherosclerosis, and its characteristics such as the extent and location (2). ccta reporting has traditionally been operator-dependent, and no precise classification has been broadly used for summarizing and categorizing cad severity in this imaging modality (3). previously, efforts had been made to design and implement uniform structuralized reporting frameworks for the interpretation of imaging assessments such as breast (bi-rads), prostate (pi-rads), liver (li-rads), and lung (lung-rads) imaging reporting and data systems (4). to this end, in 2016, the coronary artery disease reporting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 2 and data systems (cad-rads), a multi-society consensus reached by radiologists and cardiologists, was introduced to address the inconsistent ccta reports (5). cad-rads has been intended to establish a common lexicon between multiple disciplines involved in patient management. moreover, the acceptable intra and inter-observer variability of this scoring system contributed to the consistent and efficient patient clinical management and facilitated data gathering for registries with research purposes (6, 7). cad-rads provides a precise yet simple representation of cad severity by classifying patients based on the most severe stenosis identified in ccta (8). cad-rads categorizes the stenosis according to the degree of luminal diameter stenosis, ranging from the absence of any occlusion or plaque (category 0) to total occlusion of at least one coronary artery (category 5). there are also modifiers including n, s, g, and v, which stand for non-diagnostic, stent, graft, and vulnerability, respectively, providing additional details of the ccta finding (table 1) (5). in addition to the previously mentioned advantages of cadrads, its clinical meaningfulness would be pronounced when patient categorization provides guidance on their therapeutic and preventive management measures. to achieve this aim, a preliminary step is to confirm the validity of cad-rads categorization for patient prognosis. previously, several reports have investigated the predictive value of the cad-rads categorization system on patient outcomes, consisting of the risk for a major adverse cardiovascular event (mace) and all-cause mortality. this systematic review with meta-analysis aimed to comprehensively appraise all available studies and draw a conclusion on the predictive value of the cad-rads classification system in cad patients. 2. methods 2.1. study design and setting this systematic review and meta-analysis was designed to evaluate the predictive value of cad-rads in the assessment of outcomes in cad patients. in this study, pico was defined as: patients (p): patients with suspected or known coronary artery disease, index test (i): cad-rads classification tool, comparison (c): coronary artery disease patients not developing the outcome of the study, outcome (o): major adverse cardiovascular event (mace) and all-cause mortality. 2.2. search strategy appropriate keywords related to the aim of this study were chosen based on mesh (medline database) and emtree (embase database) terms, a review of the related literature, and consultation with experts in the field. a systematic search was performed using four online databases of pubmed, embase, scopus, and web of science until september 19th, 2022. the search strategy used for this study is provided in supplementary material 1. google and google scholar search engines and references of the included articles were also reviewed to retrieve any papers that might have been missed. 2.3. selection criteria all articles evaluating the value of cad-rads for the prediction of outcomes in cad patients were included in this study. the exclusion criteria were commentaries and editorials, review articles, case reports, case series, and articles not reporting the data of interest. 2.4. data collection two researchers independently reviewed the titles and abstracts of the retrieved articles and full-text screening was performed for possibly relevant articles and appropriate articles were included in the study. the information reported in the included articles was summarized and compiled in a checklist designed according to the criteria of preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. any disagreements were resolved by consulting a third reviewer. the data checklist included article characteristics (name of first author, year of publication, and country of study), study design, studied population, number of patients, number of men, age, studied outcome and number of patients developing the outcome, follow-up duration, reported cad-rads category, and the relevant effect size reported for each cad-rads category. the effect size of interest was chosen to be hazard ratio and the authors of any articles not providing required information were contacted by email, with a 1-week reminder in order to gain access to their results. any disagreement between the two reviewers was resolved by the third reviewer. 2.5. quality and certainty of evidence assessment the quality of the articles was assessed using the guidelines provided by the quality assessment of prognostic accuracy studies (quapas) tool (9). based on this guideline the articles are assessed according to their risk of bias (in domains of participants, index test, outcome, flow and timing, and analysis) and their applicability (in domains of participants, index test, outcome, and flow and timing). the grades of recommendation, assessment, development, and evaluation (grade) guidelines were used to evaluate the certainty of evidence (10). the certainty of evidence table was designed using gradepro online software (www.gradepro.org). 2.6. statistical analysis analyses were performed in the stata 17.0 statistical software. the predictive value of cad-rads for outcomes of cad patients was recorded as hazard ratio (hr) and 95% confidence interval (ci) and the data were analyzed using this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e45 table 1: cad-rads classification system category maximal stenosis interpretation cad-rads 0 0% no cad cad-rads 1 1 24% minimal nonobstructive cad-rads 2 25 49% mild nonobstructive cad-rads 3 50 69% moderate stenosis cad-rads 4a 70 99% severe stenosis cad-rads 4b left main >50% or 3-vessel ≥ 70% severe stenosis cad-rads 5 100% total coronary occlusion cad-rads: coronary artery disease-reporting and data system; cad: coronary artery disease. table 2: characteristics of included studies study, year design# sample size age* male% (n) follow-up event% (n) major adverse cardiac event (mace) altay, 2021 (12) retrospective 359 54.17 54.31 (195) 8 years 6.96 (25) bittner, 2020(13) retrospective 3840 60.4±8.2 48.64 (1868) 2.08 years 2.99 (115) duguay, 2017(20) retrospective 48 56 ± 10 60.4 (29) 1.6 year 29.16 (14) faber, 2021(21) retrospective 1615 59 66.62 (1076) 10.5 years 3.31 (51) finck. 2019 (a)(14) retrospective 2011 59 ± 11 66.03 (1328) 10 years 2.88 (58) lee, 2021(15) retrospective 1492 58±6.14 50.87 (759) 3 months 4.22 (63) 31.5 months 6.90 (103) maclean, 2022(22) retrospective 720 58 [iqr 19] 62.08 (447) 5.4 years 7.5 (54) mangalesh, 2022(23) prospective 366 62 70.76 (259) 2.56 years 16.39 (60) senoner, 2020(16) prospective 1430 57.9±11.1 55.59 (795) 10.55 years 3.98 (57) tang, 2022(17) prospective 511 61 [33-94] 75.92 (388) 1 year 6.65 (34) van rosendael, 2019(24) prospective 2134 54.72 49.01 (1046) 3.6 years 0.06 (130) williams, 2020(18) retrospective 1769 58±10 56.35 (997) 4.7 years 2.31 (41) xie, 2018(19) retrospective 5039 59.97 63.74 (3212) 5 years 15.30 (771) yamamoto, 2021(25) prospective 133 67 ± 11 69.92 (93) 3.33 years 10.52 (14) all-cause mortality finck, 2019 (b)(26) retrospective 1913 58.97 66.54 (1273) 9.7 years 5.17 (99) huang, 2021(27) retrospective 9625 59.8±10.7 44.28 (4262) 4.3 years 5.61 (540) senoner, 2020(16) prospective 1430 57.9±11.1 55.59 (795) 10.55 years 7.41 (106) xie, 2018(19) retrospective 5039 59.97 63.74 (3212) 5 years 6.23 (314) *: age is reported as mean ± sd or median [iqr]. #: all studies are observational. the “meta” package. the studies utilizing original cad-rads categories (1, 2, 3, 4a, 4b, and 5), with cad-rads category 0 as the reference, were included in the meta-analysis. the experiments with reports of combinations of the original cadrads categories into a subset category or continuous variable were excluded from the meta-analysis and have been reported qualitatively. a meta-regression analysis was performed to evaluate the effect of the follow-up duration on the predictive value of cad-rads. the heterogeneity between included studies was evaluated using i2 statistics and chisquared test. publication bias assessment was not applicable since less than 10 articles were included in each meta-analysis (11). 3. results 3.1. study characteristics the systematic search of online databases of pubmed, embase, scopus, and web of science resulted in 346 nonduplicate records. 92 of these records were deemed to be eligible and upon further evaluation, 15 articles were chosen to be included in this study. two articles were found via manual search, one of which was included. finally, 16 articles (12-27) were included in this study (figure 1). all included articles had assessed suspected or known coronary artery disease patients with a low to intermediate probability of cad. the articles had defined cad-rads categories as introduced by cury et al. (5) and only one article had a slight definition variation (5% difference in categories 1 and 2) (13). the results of analyses did not differ signifithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 4 table 3: results of miscellaneous cad-rads reporting cad-rads category study, year hazard ratio (95% ci) major adverse cardiovascular event (mace) 1 and 2 lee, 2021 (15) 2.4 (0.8-6.9) 1.5 (0.7-3.2) 2 and 3 van rosendael, 2019 (24) 1.95 (1.19-3.2) ≥3 duguay, 2017 (20) 3.12 (1.03-10.17) yamamoto, 2021 (25) 1.3 (0.16-11.1) 4 (4a and 4b) senoner, 2020 (16) 36.48 (4.94-269.67) tang, 2022 (17) 13.49 (4.809-37.86) ≥4 lee, 2021 (15) 1.7 (1.1-39.2) lee, 2021 (15) 8.5 (3.7-15.8) mangalesh, 2022 (23) 3.801 (1.58-9.145) van rosendael, 2019 (24) 2.68 (1.3-5.53) yamamoto, 2021 (25) 1.3 (0.35-5.15) 4b+5 bittner, 2020 (13) 21.84 (8.63-55.26) yamamoto, 2021 (25) 2.6 (0.72-9.2) 1.97 (1.12-3.45) male overall faber, 2021 (21) 5.34 (2.42-11.8) female 2.34 (1.23-4.45) < 65 years 2.8 (1.46-5.35) ≥65 years maclean, 2022 (22) 2.96 (2.2-4) all-cause mortality 4 (4a and 4b) huang, 2021 (27) 2.761 (1.961-3.887) 4b and 5 senoner, 2020 (16) 2.97 (1.59-5.57) overall finck, 2019 (b) (26) 2.03 (1.44-2.86) non-diabetic 1.72 (0.98-3.01) diabetic cad-rads: coronary artery disease-reporting and data system; ci: confidence interval. cantly by the inclusion of this article and thus, the record was not excluded. the characteristics of the included studies are demonstrated in table 2. 3.2. value of cad-rads in prediction of mace 14 out of the 16 included articles assessed the value of cadrads categories for the prediction of mace (12-25). 10 articles had reports of combinations of the original cad-rads categories into a subset or overall category, which were not included in the meta-analysis and are reported separately (13, 15-17, 20-25). 8 articles (12-19) were included in the meta-analysis for the evaluation of the value of original cad-rads categorization for the prediction of mace. the results of our analysis demonstrated that all the original cad-rads categories (1, 2, 3, 4a, 4b, 5) can predict mace in cad patients. the hazard ratios of cads-rads 1, 2, 3, 4a, 4b, and 5 for prediction of mace were 3.39 (95% ci: 2.19-5.23), 4.19, (95% ci: 2.93-5.99), 5.99 (95% ci: 3.83-9.38), 7.29 (95% ci: 3.54-15.02), 6.27 (95% ci: 5.02-7.84), and 8.63 (95% ci: 4.67-15.95), respectively. all the analyses were statistically significant (p < 0.0001) (figure 2), with an increase in trend in the risk of mace across cad-rads categories (regression co-efficient = 0.066; 95% ci: 0.018-0.114; p = 0.007). the follow-up of the studies ranged between 3 months to 10 years. a meta-regression analysis was performed to assess the effect of follow-up duration on the predictive value of cad-rads for mace. the results showed that the difference between follow-up durations had no significant effect on the predictive value of cad-rads in any of the categories (supplementary table 1). 3.3. value of cad-rads in the prediction of allcause mortality 4 out of the 16 included articles evaluated the value of cadrads in the prediction of all-cause mortality (16, 19, 26, 27). one article (26) only reported the results for combinations of the original cad-rads categories into a subset or overall category, which was not included in the meta-analysis and is reported qualitatively. 3 articles (16, 19, 27) had assessed the value of the original cad-rads categories in the prediction of all-cause mortality. the results of the analysis showed that all cad-rads categories, except cad-rads 1, can be a predictor of all-cause mortality. the hazard ratios of cads-rads 1, 2, 3, 4a, 4b, and 5 for prediction of all-cause mortality were 1.50 (95% ci: 0.962.34, p = 0.073), 1.85 (95% ci: 1.28-2.68, p = 0.001), 1.65 (95% ci: 1.31-2.07, p < 0.0001), 1.98 (95% ci: 1.26-3.09, p = 0.003), 2.78 (95% ci: 1.64-4.71, p < 0.0001), and 3.09 (95% ci: 1.915.01, p < 0.0001), respectively (figure 3). the analysis showed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e45 an increasing trend in the risk of all-cause mortality across cad-rads categories (regression co-efficient = 0.046; 95% ci: 0.008-0.084; p = 0.018). although it should be noted that the results of cad-rads categories 4a, 4b, and 5 should be interpreted with caution due to the limited number of studies in the respective analyses. the follow-up of the included studies varied between 4 to 10 years. a meta-regression analysis was performed to assess the effect of follow-up length on the predictive value of cadrads for all-cause mortality. due to the limited number of included studies, the analyses could only be performed on cad-rads categories 1, 2, and 3, none of which showed relations to the follow-up duration (supplementary table 2). 3.4. miscellaneous cad-rads reporting 10 articles had reports of combinations of the original cadrads categories for the prediction of mace (13, 15-17, 2025). lee et. al (15) demonstrated that a combined category of cad-rads 1 and 2 could not predict 3-month (hr = 2.4, 95% ci: 0.8-6.9) and 31.5-month (hr = 1.5, 95% ci: 0.7-3.2) mace. van rosendael et al. (24) reported that moderate cad (consisting of cad-rads 2 and 3) was not a predictor of mace (hr = 1.95, 95% ci: 1.19-3.2). two studies utilized a category of cad-rads ≥ 3 with conflicting results. duguay et al. (20) reported a hazard ratio of 3.12 (95% ci: 1.03-10.17) for this combined category in the prediction of mace, while yamamato et al. (25) did not report a predictive value of cad-rads for mace (hr = 1.3, 95% ci: 0.16-11.1). cad-rads 4 (combined category of cad-rads 4a and 4b) was utilized by two studies (16, 17), and was shown to be a predictor of mace (hr = 36.48, 95% ci: 4.94-269.67 and hr = 13.49, 95% ci: 4.809-37.86). 5 experiments had data on a combined category of cad-rads 4a, 4b and 5 (15, 2325). four of these experiments (15, 23, 24) showed that this combined cad-rads category can predict mace. two studies combined cad-rads categories 4b and 5 and reported conflicting results. bittner et al. (13) reported a hazard ratio of 21.84 (95% ci: 8.63-55.26) while yamamoto et al. (25) reported a hazard ratio of 2.6 (95% ci: 0.72-9.2) for the predictive value of this subset category for mace. two studies reported results for the predictive value of overall cad-rads. faber et al. (21) demonstrated that cad-rads as a continuous variable can be predictive of mace in males (hr = 1.97, 95% ci: 1.12-3.45), females (hr = 5.34, 95% ci: 2.42-11.8), patients < 65 years of age (hr = 2.34, 95% ci: 1.234.45) and patients ≥ 65 years of age (hr = 2.8, 95% ci: 1.465.35). maclean et al. (22) reported a hazard ratio of 2.96 (95% ci: 2.2-4) for the predictive value of overall cad-rads for the prediction of mace. three articles (16, 26, 27) had reported combinations of the original cad-rads categories for prediction of all-cause mortality. senoner et. al (16) reported that cad-rads 4 (combined cad-rads 4a and 4b) can predict all-cause mortality (hr = 2.97, 95% ci: 1.59-5.57). huang et. al (27) also reported that combined cad-rads 4b and 5 can be predictive of all-cause mortality (hr = 2.761, 95% ci: 1.961-3.887). finck et al. (26) reported that while an overall cad-rads category can be predictive of all-cause mortality in non-diabetic patients (hr = 2.03, 95% ci: 1.44-2.86), it does not predict all-cause mortality in non-diabetic patients (hr = 1.72, 95% ci: 0.98-3.01). although it should be noted that the diabetic group consisted of only 132 patients. the results of the analyses on the miscellaneous cad-rads reporting are demonstrated in table 3. 3.5. quality assessment the risk of bias was evaluated according to the guidelines of quapas. the risk of bias was assessed to be unclear in the domain of patient selection in four studies due to no report of the sampling method. seven articles were judged to have an unclear risk of bias in the domain of index test due to no mention of the specialty of the assessor. two articles were evaluated as unclear in risk of bias in the domain of outcome due to no report of mace definition and the source of gathered data (registries, medical records, etc.). all articles were judged to have a high risk of bias in the flow and timing domain. however, considering that according to guidelines the treatment of coronary artery disease patients varies depending on its severity, clinical management of cad patients cannot be identical and thus, the risk of bias in the domain of flow and timing was decided to be excluded from the judgment of overall risk of bias. one study was found to have a high risk of bias in the domain of analysis due to a high loss to follow-up rate. studies were rated as low in all other domains of risk of bias assessment. one study was judged to have unclear applicability in the domain of outcome due to non-informative outcome definition. studies were assessed to have no concerns in applicability in other domains (table 4). 3.6. certainty of evidence all included studies were observational studies and the base level of evidence was set as low. the level of evidence for the outcome of mace was reduced by two grades due to considerable risk of bias and observed heterogeneity in the analysis. it was increased by two grades due to the observed large magnitude of effect (hr > 2) and possible dose-response gradient observed and thus, the level of evidence for the outcome of mace was judged to be low. the level of evidence for the outcome of all-cause mortality was decreased by two grades due to the considerable risk of bias and imprecision (wide cis) and increased by one due to the possible dose-response this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 6 table 4: risk of bias assessment study, year risk of bias applicability overall patient selection index test outcome flow and timing* analysis patient selection index test outcome flow and timing altay, 2021 (12) unclear low unclear high low low low unclear low some concern bittner, 2020 (13) low low low high low low low low low low duguay, 2017 (20) unclear low low high low low low low low some concern faber, 2021 (21) low unclear low high low low low low low some concern finck, 2019 (a) (14) low unclear low high low low low low low some concern finck, 2019 (b) (26) low unclear low high low low low low low some concern huang, 2021 (27) low unclear low high low low low low low some concern lee, 2021 (15) unclear low low high low low low low low some concern maclean, 2022 (22) low unclear low high low low low low low some concern mangalesh, 2022 (23) unclear low unclear high low low low low low some concern senoner, 2020 (16) low low low high low low low low low low tang, 2022 (17) low low low high high low low low low some concern van rosendael, 2019 (24) low low low high low low low low low low williams, 2020 (18) low unclear low high low low low low low some concern xie, 2018 (19) low unclear low high low low low low low some concern yamamoto, 2021 (25) low low low high low low low low low low *flow and timing domain was judged to be of high risk of bias due to differences in treatment of coronary artery disease patients; however, considering that according to guidelines the treatment of coronary artery disease patients varies depending on its severity, the bias in flow and timing domain was excluded from the judgment of overall risk of bias. gradient. the level of evidence for the outcome of all-cause mortality was judged to be very low (table 5). 4. discussion this systematic review and meta-analysis examined the effectiveness of hierarchical cad-rads categorization in predicting mace and all-cause mortality in cad patients. according to our analysis, all original cad-rads categories can be used as a predictor of mace, and all categories, except cad-rads 1, can be a predictor of all-cause mortality. moreover, patients with higher cad-rads categories had a higher risk of unfavorable outcomes. our results confirm that cadrads categorization of ccta findings is valid for prognostication of cad patients’ outcomes, which is consistent with other scores such as modified duke index (28). the results of our analysis demonstrate that cad-rads categories 1 and 2, which are representative of non-obstructive cad patients (less than 50% stenosis), are associated with an increased risk of unfavorable outcomes. studies have shown that non-obstructive cad is attributable to mace in acute coronary syndrome patients treated with percutaneous coronary intervention and that non-obstructive cad in ccta should be considered as a clinically important finding (29, 30). this implies that the previous concept of dichotomization of cad patients into an obstructive and non-obstructive group, may not be informative enough for the prediction of patient outcomes, and preventative and treatment strategy decision-making should not solely rely on the degree of obstruction and various variables such as plaque characteristics should also be taken into account. contrary to the results of the meta-analysis of the original cad-rads categories, the results of the articles utilizing a combination of cad-rads categories were less conclusive on their predictive value due to having wider cis and reports of insignificant predictive value for higher cad-rads categories. however, it should be noted that the references for the analyses of the combined cad-rads categories differed among studies and the studies not demonstrating a predicthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e45 table 5: certainty of evidence total knowledge score hazard ratio (95% ci) certainty number of studies risk of bias inconsistency indirectness imprecision other considerations mace (follow-up: range 1 month to 10 years) 8 studies serious seriousa not serious not serious large magnitude of effect possible dose response gradient cad-rads 1: 3.39 (95% ci: 2.19-5.23) cad-rads 2: 4.19 (95% ci: 2.93-5.99) cad-rads 3: 5.99 (95% ci: 3.83-9.38) cad-rads 4a: 7.29 (95% ci: 3.54-15.02) cad-rads 4b: 6.27 (95% ci: 5.02-7.84) cad-rads 5: 8.63 (95% ci: 4.67-15.95) ⊕⊕©© low all-cause mortality (follow-up: range 6 months to 8 years) 3 studies serious not serious not serious seriousb possible dose response gradient cad-rads 1: 1.50 (95% ci: 0.96-2.34) cad-rads 2: 1.85 (95% ci: 1.28-2.68) cad-rads 3: 1.65 (95% ci: 1.31-2.07) cad-rads 4a: 1.98 (95% ci: 1.26-3.09) cad-rads 4b: 2.78 (95% ci: 1.64-4.71) cad-rads 5: 3.09 (95% ci: 1.91-5.01) ⊕©©© very low cad-rads: coronary artery disease-reporting and data system; mace: major adverse cardiac event; ci: confidence interval. a. there was considerable heterogeneity among the studies. b. wide cis tive value for the cad-rads category had smaller sample sizes. this finding implies that cad-rads might be better utilized as the original separate categories and attempts of combining these categories (even only combining categories 4a and 4b) could reduce the accuracy of the classification system. however, it should be kept in mind that few studies with limited sample sizes had evaluated combinations of cad-rads categories. the included studies had different durations of follow-up, however, our analysis indicated that follow-up had no effect on the predictive value of cad-rads for mace and all-cause mortality. faber et al. (21) evaluated the predictive value of cad-rads for mace in male and female populations and demonstrated that cad-rads as a continuous variable might be a better predictive tool in the female rather than the male population. articles have demonstrated that the female cad population has higher mortality than the male counterparts, which could explain the higher hr reported for the female population (31). further studies could shed more light on the differences in the predictive value of cad-rads in male and female populations. the fundamental parameter for the categorization of ccta in cad-rads is the luminal diameter of the most stenotic vessel and post-ccta recommendation on the further diagnostic test and management depends on the mere cadrads category. unlike other scoring indices such as the duke index, cad-rads ignores the number of involved vessels and the location of the culprit lesion. as a result, the cadrads category cannot replace the ccta report and should be interpreted in conjunction with the detailed ccta report. evidence indicates that along with dimensional parameters of coronary atherosclerotic lesions, plaque characteristics also play a pivotal role in risk prediction of cad patients (32, 33). cad-rads reflects plaque characterization through an extra modifier that assesses the presence of vulnerable or high-risk plaque. in our review, due to the unavailability of data, we could not perform an analysis on the effect of such this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 8 additional modifiers on patients’ risk of mace and mortality. it can be assumed that detailed categorization of ccta findings in addition to cad-rads scoring may yield more prognostic information than what is presented in our study. although the cad-rads was not designed to take the place of the complete descriptive reports of ccta, the lack of incorporation of such contributing factors may render ccta’s rich data obsolete. nevertheless, the structuralized reporting of ccta using cad-rads and the discrete prognostic value of each category will lead to better patient care by consolidating the communication between referring and interpreting physicians (34). to improve the representativeness of cadrads categorization, cad-rads 2.0 (35) was introduced in 2022, which incorporates parameters reflecting plaque burden and ischemia in the form of modifiers added to stenosis assessment. this could improve the decision-making process for cad patients by better representing the extent of cad and the lesions’ characteristics. yet, cad-rads’s shortcoming remains due to the fact that it cannot be used to evaluate the number of involved vessels. this reduces the effectiveness of the cad-rads classification system in predicting outcomes and progression in patients with multiple vessels involved (36). with the latest advancements in image processing, there is potential for the addition of other parameters related to atherosclerosis pathogenesis, including pericardial fat attenuation (37), to enhance the precision of prognostic and diagnostic performance of the cad-rads scoring system. in this regard, machine learning was shown to be promising in integrating multiplex ccta parameters with both other performed test variables and patient characteristics. this would enable individualized and highly accurate risk prediction, which would significantly impact delivering optimal patient care (38, 39). moreover, besides risk stratification, the cad-rads scoring system recommends further test studies and treatment plans for each cad-rads category. although these recommendations are derived from expert consensus, since there currently are scarce evidence on the treatment strategies of cad-rads guidelines, the treating physician should implement an individualized treatment plan for each patient and not solely rely on the recommendations provided by cadrads guidelines. future studies should investigate the effectiveness of these treatment plans on the disease progression of patients. 5. limitations we acknowledge that our study has limitations. the definition of mace varied between the studies, which limits accurate comparison of the studies. a recent systematic review (40) has shown that only a limited number of studies match the conventional mace definition of acute myocardial infarction, stroke, and cardiovascular death. since the definitions vary slightly between studies, all reports of mace were pooled and analyzed together. also, not all the included studies specified whether the included patients were acute or chronic cad patients or whether the patients were symptomatic or asymptomatic, which might lead to different prognoses and treatment plans. further studies should more accurately specify the patient population and compare the predictive capabilities of cad-rads in acute and chronic cad patients. also, a major contributor to the outcome of cad patients is the treatment strategies devised for the patients, which was not reported in the included articles and may vary depending on national and institutional guidelines. 6. conclusion low to very low levels of evidence demonstrated that the cad-rads classification system can be used to predict outcomes of mace and all-cause mortality. this indicates that the implementation of cad-rads into clinical practice, besides enhancing the communication between physicians and improving patient care, can also guide physicians in risk assessment of the patients’ prognosis. further well-designed clinical trials or prospective cohort studies are needed to provide a high level of evidence for predicting the value of cadrads in cad patients. 7. declarations 7.1. acknowledgments not applicable. 7.2. conflict of interest the authors declare that they have no competing interests. 7.3. fundings this study was funded by shahid beheshti university of medical sciences (grant no. 43005143). 7.4. authors’ contribution study design: my, rm data gathering: mr, ka analysis: my, ka interpretation of results: all authors drafting and revising: all authors 7.5. availability of data and materials the gathered data and checklist can be provided to qualified researchers with the intent of replicating the procedure and results. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e45 references 1. abdelrahman km, chen my, dey ak, virmani r, finn av, khamis ry, et al. coronary computed tomography angiography from clinical uses to emerging technologies: jacc state-of-the-art review. j am coll cardiol. 2020;76(10):1226-43. 2. cordeiro ma, lima ja. atherosclerotic plaque characterization by multidetector row computed 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cardiovascular diseases: impact on clinical manifestations, management, and outcomes. eur heart j. 2016;37(1):2434. 32. gossl m, versari d, hildebrandt h, mannheim d, olson ml, lerman lo, et al. vulnerable plaque: detection and management. med clin north am. 2007;91(4):573-601. 33. finn av, nakano m, narula j, kolodgie fd, virmani r. concept of vulnerable/unstable plaque. arterioscler thromb vasc biol. 2010;30(7):1282-92. 34. canan a, ranganath p, goerne h, abbara s, landeras l, rajiah p. cad-rads: pushing the limits. radiographics. 2020;40(3):629-52. 35. cury rc, leipsic j, abbara s, achenbach s, berman d, bittencourt m, et al. cad-rads 2.0 2022 coronary artery disease-reporting and data system: an expert consensus document of the society of cardiovascular computed tomography (scct), the american college of cardiology (acc), the american college of radiology (acr), and the north america society of cardiovascular imaging (nasci). j cardiovasc comput tomogr. 2022;16(6):536-57. 36. szilveszter b, vattay b, bossoussou m, vecsey-nagy m, simon j, merkely b, et al. cad-rads may underestimate coronary plaque progression as detected by serial ct angiography. eur heart j cardiovasc imaging. 2022;23(11):1530-9. 37. antonopoulos as, sanna f, sabharwal n, thomas s, oikonomou ek, herdman l, et al. detecting human coronary inflammation by imaging perivascular fat. sci transl med. 2017;9(398):eaal2658. 38. cormode dp, roessl e, thran a, skajaa t, gordon re, schlomka jp, et al. atherosclerotic plaque composition: analysis with multicolor ct and targeted gold nanoparticles. radiology. 2010;256(3):774-82. 39. kolossvary m, karady j, szilveszter b, kitslaar p, hoffmann u, merkely b, et al. radiomic features are superior to conventional quantitative computed tomographic metrics to identify coronary plaques with napkin-ring sign. circ cardiovasc imaging. 2017;10(12):e006843. 40. bosco e, hsueh l, mcconeghy kw, gravenstein s, saade e. major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review. bmc med res methodol. 2021;21(1):241. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e45 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) diagram. supplementary material 1: search strategy for the “evaluation of the value of coronary artery disease – reporting and data system (cadrads) in outcome prediction of coronary artery disease patients” (septemeber 19t h , 2022) pubmed: cad-rads [tiab] or [tiab] cad rads[tiab] or cadrads[tiab] or coronary artery disease reporting and data system[tiab] or coronary artery disease reporting[tiab] embase: ‘coronary artery disease reporting and data system’/exp or ‘cad-rads’:ab,ti or ‘cad rads’:ab,ti or ‘cadrads’:ab,ti or ‘coronary artery disease reporting’:ab,ti web of science: (all=("coronary artery disease reporting and data system" or "cad-rads" or "cad rads" or "cadrads" or "coronary artery disease reporting")) scopus: title-abs-key ("coronary artery disease reporting and data system" or "cad-rads" or "cad rads" or "cadrads" or "coronary artery disease reporting") supplementary table 1: meta-regression for evaluation of effect of follow-up on predictive performance of cad-rads for major adverse cardiovascular event (mace) variable meta-regression coefficient 95% confidence interval p value cad-rads 1 1.00975 0.99771, 1.02193 0.113 cad-rads 2 1.00461 0.99264, 1.01671 0.452 cad-rads 3 1.00492 0.99291, 1.01708 0.423 cad-rads 4a 1.00490 0.97994, 1.03050 0.703 cad-rads 4b 1.00441 0.99411, 1.01482 0.402 cad-rads 5 1.01510 0.99035, 1.04047 0.234 cad-rads: coronary artery disease-reporting and data system. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 12 figure 2: value of cad-rads classification system in prediction of major adverse cardiovascular events in coronary artery disease patients. cad-rads: coronary artery disease-reporting and data system; ci: confidence interval; hr: hazard ratio. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e45 figure 3: value of cad-rads classification system in prediction of all-cause mortality in coronary artery disease patients. cad-rads: coronary artery disease-reporting and data system; ci: confidence interval; hr: hazard ratio. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. ahmadzadeh et al. 14 supplementary table 2: meta-regression for evaluation of effect of follow-up on predictive performance of cad-rads for all-cause mortality variable meta-regression coefficient 95% confidence interval p value cad-rads 1 1.00573 0.98776, 1.02402 0.534 cad-rads 2 1.00615 0.99350, 1.01897 0.342 cad-rads 3 1.00551 0.99266, 1.01853 0.402 cad-rads 4a not assessable due to limited number of studies cad-rads 4b not assessable due to limited number of studies cad-rads 5 not assessable due to limited number of studies cad-rads: coronary artery disease-reporting and data system. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 81 emergency (2014); 2 (2): 81-84 original research diagnostic accuracy of ultrasonography in the initial evaluation of patients with penetrating chest trauma farhad heydari, mehrdad esmailian, masoumeh dehghanniri* department of emergency medicine, isfahan university of medical sciences, isfahan, iran abstract introduction: traumatic chest injuries (tci) are one of the most common causes of referring to the emergency departments, with high mortality and disability. this study was designed to evaluate the diagnostic accuracy of ultrasonography versus chest x ray (cxr) in detection of hemo-pneumothorax for patients suffering penetrating tci. methods: the present cross-sectional study was performed to evaluate the diagnostic accuracy of ultrasonography in penetrating tci victims referred to the emergency department of shahid kashani and alzahra hospitals of isfahan, iran, from july 2012 to june 2013. bedside ultrasonography and plain cxr was done on arrival and three hours after admission. the results of ultrasonography and radiography were separately evaluated by an emergency medicine specialist and a radiologist, who were blind to the aims of the study. then, sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), and kappa coefficient was considered to evaluate the accuracy of ultrasonography. results: in this research, 64 patients with penetrating chest trauma were assessed (98.4% male). the mean age of them was 25.6±8.5 years (rang: 13-65). the plain radiography revealed the eight (12.5%) cases of pneumothorax and one (1.6%) hemothorax. the findings of primary ultrasonography also showed the same number of hemo-pneumothorax. sensitivity and specificity of primary ultrasound in diagnosis of pneumothorax were 100% (95% cl: 60.7100) and 100.0% (95% cl, 92.0% to 100.0%) and in detection of hemothorax were 100% (95% cl: 50.5-100) and 100% (95% cl: 92.8-100), respectively. sensitivity and specificity of ultrasound in the third hour were 100% (95% cl: 31.3-100) and 100% (95% cl: 91.4-100), respectively. conclusion: findings of the present study have shown that ultrasonography has an acceptable diagnostic accuracy in the initial assessment of patients with penetrating chest trauma. however, because of its dependency on operator proficiency and other limitations more studies are needed in this area. key words: thoracic injuries; trauma; diagnostic evaluation; ultrasonography; radiography cite this article as: heydari f, esmailian m, dehghanniri m. diagnostic accuracy of ultrasonography in the initial evaluation of patients with penetrating chest trauma. emergency. 2014;2(2):81-4. introduction:1 raumatic chest injuries (tci) are one of the most common causes of referring to the emergency departments, with high mortality and disability (1). of all these traumatic injuries penetrating traumas cause more complications (2). pneumothorax and hemothorax are the most important and prevalent problems seen in a remarkable percent of these patients (3). although pneumothorax and medium hemothoraxes did not life-threatening, tension hemopneumothorax could accompany with harmful conditions such as cardiac arrest (4). therefore, a prompt diagnosis and treatment of these patients could improve their conditions considerably. chest radiography (cxr) and computed tomography (ct) scan are two *corresponding author: masoumeh dehghanniri; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989131585086; fax:+983116685555 email: dr.dehghanniri@yahoo.com received: 13 march 2014; accepted: 16 may 2014 important diagnostic tools used for detecting these injuries. however, missing of about half of all pneumothoraxes by radiography caused that ct scan has been shown as a gold standard tool for detection of chest injuries (5). however, most patients did not have the ct indications and on the other hand, using this diagnostic test is time consuming and leads to delay in diagnosis of patients. thus, today radiography is used as the initial diagnostic test in patients with tci. even though radiography is a non-invasive and inexpensive tool, using it in all patients suffering trauma lead to considerable increase in treatment costs, exposure of patients to radiation, and crowdedness of emergency department (6). ultrasound is maybe a reliable alternative for radiography. using ultrasound because of its high speed in diagnosis and portable property causes that it turn to be the first step in diagnosis of many clinical conditions (7). however, the diagnostic accuracy of ultrasonography much depends on the operator proficiency and it is t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com heydari et al 82 not adequately reliable in diagnosis of parenchymal injuries and those with no hemorrhage or free flow liquid (8-12). nevertheless, structural changes occurred in ultrasonography equipment, leads to improve the quality of ultrasound image and particularly its spatial resolution. therefore, that with a brief training for physicians the diagnostic sensitivity of this test could be increased enough. these changes cause patients, especially those who are hemodynamically unstable, have been treated in the least possible time (13). recent studies have also shown high sensitivity and specificity of ultrasound in comparison with radiography in detecting of tci (5, 14). considering all above mentioned, this study was designed to evaluate the diagnostic accuracy of ultrasonography versus cxr in detection of hemo-pneumothorax for patients suffering penetrating tci. methods: study design and setting this project is a cross-sectional study designed to evaluate the diagnosis accuracy of ultrasonography versus cxr in detection of hemo-pneumothorax for patients suffering penetrating tci, referred to shahid kashani and alzahra hospitals of isfahan, iran, from july 2012 to june 2013. data gathering and ultrasonography was done by an emergency medicine specialist. cxr findings were interpreted by a radiologist who was blind to clinical and ultrasonographic findings. the protocol of this study was reviewed and approved by isfahan university of medical sciences ethics committee. during the study, researchers committed to the principles of helsinki protocol. this study had no interference with treatment process of patients. before doing the project, the patients signed the informed consent form. participants in this review, the patients with penetrating tci were enrolled. the exclusion criteria concluded pregnancy, non-penetrating trauma, hemodynamic instability, respiratory distress and asthma, diminished lung sounds, limiting of damage to the skin and subcutaneous, and not satisfaction of participation. sample selection was done consecutively. to identify the sample volume, considering to 80% prevalence of normal cxrs in patients with penetrating tci (14), taking 95% confidence interval (α=0.05) , 97% power (β=0.1), and 1% maximum error (d=0.1) in estimation of lesion prevalence, 62 samples were taken as a minimum required sample. measurements the emergency specialist prospectively evaluated the clinical and demographic (age, sex, and trauma location) information of patients and recorded them to the gathering form. after data gathering, the patient immediately underwent cxr. lateral and anterposterior cxr was performed in standing position. then, ultraultrasonography evaluation was done by a trained emergency medicine specialist with bedside ultrasound machine (honda hs-2000, japan), using micro-convex transducer (2-4 mhz). assessments were done based on four sections of each hemi thorax concluded: 1. the second intercostal space in the midclavicular line, 2. the fourth intercostal space in the anterior axillary line, 3. the sixth intercostal space in the midaxillary line, and 4. the sixth intercostal space in the posterior axillary line. finally, according to protocols for patients who their primary graphy was normal, the control cxr was requested next three hours (15). after cxr, the patient underwent chest ultrasonography. all radiography clichés was interpreted and recorded in separate forms by a radiologist who was blind to clinical and ultrasonographic findings. statistical analysis data was entered to the spss program (version 21.0). based on cxr findings final diagnosis of chest injury was done. the results were reported as a frequency and percentage. sensitivity, specificity, positive likelihood ratio (plr), negative likelihood ratio (nlr), positive predictive value (ppv), and negative predictive value (npv) of ultrasonography in detection of hemopneumothorax were separately evaluated in both of times mentioned above. in addition, cohen's kappa coefficient was used for analysis of similarities between the results of cxr and ultrasonography. in all cases p<0.05 was considered as significant. results: finally, 64 patients were enrolled the study (98.4% male). the mean age of subjects was 25.6± 8.5 years (range: 13-61). the injury in 30 patients (46.9%) was in upper-posterior quarter of rib cage (table1). the initial radiographic findings revealed that eight patients (12.5%) had pneumothorax and one (1.6%) hemothorax. in addition, the primary ultrasonography showed table1: demographic variables of studied patients  variability frequency (%) age (year) <18 5 (7.8) 18-39 55 (85.9) 41-60 3 (4.7) >60 1 (1.6) sex male 63 (98.4) female 1 (1.6) location of injury upper anterior quadrant 11 (17.2) posterior upper quadrant 30 (46.9) lower anterior quadrant 1 (1.6) posterior inferior quadrant 6 (9.4) diffuse injury 16 (25.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 83 emergency (2014); 2 (2): 81-84 the same findings. accordingly, sensitivity and specificity of primary ultrasonography for detection of pneumothorax in patients suffered penetrating tci was respectively achieved 100% (95% cl: 60.7-100) and 100% (95% cl: 92100). in addition, sensitivity and specificity of primary ultrasonography for detection of hemothorax were 100% (95% cl: 50.5100) and 100% (95% cl: 92.8-100), respectively (table2). the agreement between two tests was 100%. kappa cohen's coefficient was 1 (95% cl: 89100), representative a 100% inter raterreliability between two tests. after three hours for 55 patients, who had normal findings of primary cxr, the control graphy was requested. among them, three (5.2%) additional pneumothoraxes were detected. ultrasonography after three hours also showed the same numbers of pneumothoraxes. thus, the sensitivity and specificity of ultrasonography after three hours were 100 (95%cl: 31.1100) and 100% (95% cl: 91.4100), respectively (table 2). at this time, the agreement of these two tests was 100%. in addition, kappa cohen's coefficient was 1 (95%cl: 87-100), representative a 100% inter raterreliability between two tests. discussion: the findings of the present study have shown that the accuracy of ultrasonography in the initial assessment of patients referred with penetrating tci is completely similar to radiography. sensitivity and specificity of ultrasonography in detection of pneumothorax and hemothorax was 100%. it was confirmed by other studies that revealed the high sensitivity and specificity of ultrasonography in detecting pneumothorax. for instance, knudtson and his colleges in evaluation of 328 patients showed 99.7% sensitivity and specificity of ultrasonography in diagnosis of pneumothorax (14). kirkpatrick and his colleges demonstrated that although the sensitivity of ultrasonography in diagnosis of tci is 48.8%, this diagnosis test has more sensitivity in comparison with radiography. it is worth noting that the specificity of ultrasonography in detection of pneumothorax was 99.1% (5). hyacinthe and colleges showed that diagnostic accuracy of chest ultrasonography is more than cxr; so that sensitivity and specificity of ultrasonography in detection of chest injuries have a range of 37% to 61% and 61% to 96%, respectively (16). however, gentry wilkerson and stone in their studies reported a sensitivity of 85% to 100% for ultrasonography detection in chest injuries. other studies also revealed the similar findings (17-20). as can be seen, there are lots of variability in studies’ findings, which arises more from differences in study methodology because of using the portable graphies. since sensitivity and specificity of portable graphies in detection of pneumothorax and hemothorax are less than standing radiography, these differences are justified. this is the cause of difference between the present study and findings of kirkpatrick (5) and hyacinthe (16). however, generally most of studies stated that ultrasonography is the better diagnostic test versus radiography in detection of tci. based on these studies, advanced trauma life support (atls) suggested that ultrasonography could be used in the initial assessment of some conditions like the presence of free fluid, organ damage, and pneumothorax. the sensitivity of cxr for detection of pneumothorax and hemothorax is low. the results of the present study revealed that ultrasonography has a similar diagnostic accuracy to chest radiography. one of the limitations in the present project was the low sample size. as a result, the 95% confidence interval of findings has a very wide range specifically for sensitivity. on the other hand, in the present study radiography table 2: accuracy of ultrasonography in detection of pneumothorax and hemothorax  index baseline after three hours pneumothorax (95% ci)a sensitivity 100 (60.7-100) 100 (31.3-100/0) specificity 100 (92-100) 100 (91.4-100/0) positive predictive value 100 (60.7-100) 100 (31.3-100/0) negative predictive value 100 (92-100) 100 (91.4-100/0) positive likelihood ratio -------- negative likelihood ratio 1 (0.92-1) 1 (0.92-1) hemothorax (95% ci)b sensitivity 100 (50.5-100) ---- specificity 100 (92.8-100) ---- positive predictive value 100 (50.5-100) ---- negative predictive value 100 (92.8-100) ---- positive likelihood ratio -------- negative likelihood ratio 1 (0.93-1) ---- a ci: confidence interval b the blank cells are representative the lack of any detectable case of hemothorax ultrasonography or chest x-ray three hours after observation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com heydari et al 84 was used as a golden standard. by doing control ultrasonography and radiography three hours after the initial assessments of imaging, three additional pneumothoraxes were added to the abnormal findings. if ct scan was applied, it was probable that occult pneumothoraxes or hemothoraxes was detected and it could be lead to change the findings. conclusion: the results of this study has shown that ultrasonography in the initial assessments of patients with penetrating tci has an acceptable diagnostic accuracy. however, because of its dependency on operator proficiency and other limitations more studies are needed in this area. acknowledgments: the authors appreciate the insightful cooperation of medical sciences and the staffs of the emergency department of al-zahra hospital, isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. keough v, pudelek b. blunt chest trauma: review of selected pulmonary injuries focusing on pulmonary contusion. aacn adv crit care. 2001;12(2):270-81. 2. cury f, baitello al, echeverria rf, espada pc, pereira de godoy jm. rates of thoracic trauma and mortality due to accidents in brazil. ann thorac med. 2009;4(1):25-6. 3. di bartolomeo s, sanson g, nardi g, scian f, michelutto v, lattuada l. a population-based study on pneumothorax in severely traumatized patients. j trauma. 2001;51(4):677-82. 4. richardson jd, miller fb. injury to the lung and pleura. in: felician dv, moore ee, mattox kl, editors. trauma. 3 ed. stamford, ct: appelton & lange; 1996. p. 387-407. 5. kirkpatrick aw, sirois m, laupland kb, et al. hand-held thoracic sonography for detecting post-traumatic pneumothoraces: the extended focused assessment with sonography for trauma (efast). j trauma. 2004;57(2):28895. 6. levy ja, noble ve. bedside ultrasound in pediatric emergency medicine. pediatrics. 2008;121(5):e1404-e12. 7. michalke ja, rocovich c, patel t, et al. an overview of emergency ultrasound in the united states. world. 2012;3(2):85-90. 8. poletti pa, kinkel k, vermeulen b, irmay f, unger pf, terrier f. blunt abdominal trauma: should us be used to detect both free fluid and organ injuries? . radiology. 2003;227(1):95-103. 9. poletti pa, mirvis se, shanmuganathan k, et al. blunt abdominal trauma patients: can organ injury be excluded without performing computed tomography? j trauma acute care surg. 2004;57(5):1072-81. 10. mcgahan jp, wang l, richards jr. from the rsna refresher courses focused abdominal us for trauma. radiographics. 2001;21(suppl 1):s191-s9. 11. esmailian m, zargarbashi eh, masoumi b, karami m. accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures. emergency. 2013;1(1):7-10. 12. amini a, eghtesadi r, feizi am, et al. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. emergency. 2013;1(1):15-9. 13. brown ma, casola g, sirlin cb, patel ny, hoyt db. blunt abdominal trauma: screening us in 2,693 patients. radiology. 2001;218(2):352-8. 14. knudtson jl, dort jm, helmer sd, smith rs. surgeonperformed ultrasound for pneumothorax in the trauma suite. j trauma. 2004;56(3):527-30. 15. marx j, hockberger r, walls r. rosen's emergency medicine-concepts and clinical practice: elsevier health sciences; 2013. 439 p. 16. hyacinthe a-c, broux c, francony g, et al. diagnostic accuracy of ultrasonography in the acute assessment of common thoracic lesions after traumaultrasonography in thoracic trauma. chest journal. 2012;141(5):1177-83. 17. soldati g, testa a, silva fr, carbone l, portale g, silveri ng. chest ultrasonography in lung contusion. chest. 2006;130(2):533-8. 18. brooks a, davies b, smethhurst m, connolly j. emergency ultrasound in the acute assessment of haemothorax. emerg med j. 2004;21(1):44-6. 19. soldati g, testa a, sher s, pignataro g, la sala m, silveri ng. occult traumatic pneumothoraxdiagnostic accuracy of lung ultrasonography in the emergency department. chest. 2008;133(1):204-11. 20. zhang m, liu z-h, yang j-x, et al. rapid detection of pneumothorax by ultrasonography in patients with multiple trauma. critical care. 2006;10(4):r112. archives of academic emergency medicine. 2023; 11(1): e30 rev i ew art i c l e diagnostic accuracy of ottawa knee rule for diagnosis of fracture in patients with knee trauma; a systematic review and meta-analysis seyyed-morteza kazemi1, roya khorram2, ehsan fayyazishishavan3, reza amani-beni4, yas haririan5, seyed mehdi hosseini khameneh1, erfan rahmani6, reza minaei noshahr1, mahshad sarikhani7, rana rahimi7, sara saeidi8, diba saeidi8, mehrdad farrokhi9∗ 1. bone joint and related tissues research center, akhtar orthopedic hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of orthopedics, shiraz university of medical sciences, shiraz, iran. 3. department of biostatistics and data science, school of public health, the university of texas health science center at houston (uthealth), houston, tx 77030, usa. 4. medical student, school of medicine, isfahan university of medical sciences, isfahan, iran. 5. school of medicine, shiraz university of medical sciences, shiraz, iran. 6. school of medicine, tehran university of medical sciences, tehran, iran. 7. school of medicine, shahid beheshti university of medical sciences, tehran, iran. 8. students research committee, faculty of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran. 9. eris research institute, tehran, iran. received: january 2023; accepted: february 2023; published online: 3 april 2023 abstract: introduction: in order to improve the efficacy of requesting knee radiography and reduce unnecessary radiation exposure, some clinical decision rules have been proposed for the assessment of knee injuries. among them, the ottawa knee rule (okr) was considered as one of the best guidelines with several validation studies. therefore, in this meta-analysis, we aimed to investigate the accuracy of okr for diagnosis of fracture in patients presenting with knee trauma. methods: a systematic search was conducted in pubmed, web of science, scopus, google scholar, and ebsco from inception to september 2022. quality assessment of the included studies was performed using quadas-2 tool. diagnostic accuracy parameters were analyzed using random-effects model. statistical analysis was performed using meta-disc and stata softwares. results: the meta-analysis of the 18 included studies (6702 patients) showed that the pooled sensitivity and specificity of okr for diagnosis of fractures were 0.98 (95% ci: 0.96-0.99) and 0.43 (95% ci: 0.42-0.45), respectively. the pooled positive likelihood ratio (plr) and negative likelihood ratio (nlr) were 1.56 (95% ci: 1.39-1.75) and 0.12 (95% ci: 0.05-0.26), respectively. the area under curve (auc) of the hierarchical summary receiver operating characteristic (hsroc) curve was 0.54. conclusion: this meta-analysis indicates that okr has a high diagnostic performance for diagnosis of fracture, with a pooled sensitivity of 98% and a pooled specificity of 43%. these results propose potential effects of okr on reduction of unnecessary radiography, time spent in emergency departments, and direct and indirect costs, which should be confirmed using high-quality studies in the future. keywords: clinical decision rules; knee injuries; radiography cite this article as: kazemi s-m, khorram r, fayyazishishavan e, amani-beni r, haririan y, et al. diagnostic accuracy of ottawa knee rule for diagnosis of fracture in patients with knee trauma; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e30. https://doi.org/10.22037/aaem.v11i1.1934. ∗corresponding author: mehrdad farrokhi; eris research institute, tehran, iran. email: dr.mehrdad.farrokhi@gmail.com. phone number: +989384226664, fax: +989384226664, orcid: https://orcid.org/0000-00021559-2323. 1. introduction acute knee pain and trauma are known as prevalent complaints in emergency departments and account for a considerable number of plain radiography requests (1-4). despite the high number of patients presenting with acute knee pain this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 2 or trauma, less than 7% of these cases actually have a definite fracture (5, 6). indeed, radiography is commonly requested as a standard diagnostic tool for more than 90% of these suspected cases. therefore, the high rate of unnecessary radiography for detecting fractures in patients with acute knee trauma results in significantly increased medical costs along with extended hospital stay and also unnecessary radiation exposure (7, 8). in order to improve the efficacy of requesting radiography and reduce unnecessary radiation exposure, some clinical decision rules have been proposed for the assessment of knee injuries. among them, the ottawa knee rule (okr) was considered as one of the best guidelines with several validation studies. the rules have been developed to improve the efficacy with which knee traumas are assessed and to reduce unnecessary radiography without an increase in the rate of missed fractures. the okr was designed in 1995 by stiell et al. (2) as a diagnostic tool to divide cases of acute knee injury into two groups including cases who are likely to have an important bony injury and need evaluation using radiography and cases who are not likely to have a significant fracture and do not require radiography. suspected cases are highly likely to have a significant fracture and thus need a radiographic evaluation if at least one of the following criteria is positive: age at least 55 years old, isolated tenderness of patella, inability to flex the knee to 90 degrees, tenderness of fibular head, and inability to bear weight following the trauma and admission to the emergency department (2). several studies have investigated the validation of okr in patients with knee trauma, which showed high sensitivity and moderate specificity for application of this rule in emergency departments (9-12). the okr can rule out fractures and reduce unnecessary exposure to ionizing radiation with high sensitivity. however, these validation studies reported a wide range of test sensitivities and specificities in adults. therefore, in this systematic review and meta-analysis, we aimed to investigate the accuracy of okr for diagnosis of fracture in patients with knee trauma. 2. methods 2.1. search strategy this study was carried out according to the recommendations of preferred reporting items for systematic reviews and meta-analyses of diagnostic test accuracy studies (prisma-dta). a systematic search was conducted in pubmed, web of science, scopus, google scholar, and ebsco from their inception to september 2022. the search was carried out without limitations on language or the date of the published papers to ensure that all eligible studies were included in the meta-analysis. the following mesh terms and keywords and also their combinations were used in english: “ottawa” or “knee” or “rule” or “ottawa knee rule” and “knee injury” or “knee trauma” and “radiography” or “radiograph” or “x-ray”. 2.2. eligibility criteria the specific inclusion criteria for the meta-analysis were as follows: (a) diagnostic accuracy parameters of okr for diagnosis of fractures (true positive [tp], true negative [tn] and/or false positive [fp], and false negative [fn]) were reported; (b) the study population consisted of at least 10 cases with knee injury; (c) all fractures were confirmed using radiography; (d) the study has cross-sectional, case-control, or cohort design. the papers were excluded from the metaanalysis based on the following criteria: (a) solely the sensitivity and specificity of okr were provided; (b) reviews, metaanalyses, poster presentations, editorials, case reports, and cases series with fewer than 10 cases with knee injury; (c) duplicate studies. 2.3. data extraction and quality assessment the following variables from the individual papers were extracted by two independent authors using an excel spreadsheet: diagnostic accuracy parameters including tp, tn, fp, and fn, first author, year of publication, country, study design, sample size, and reference standard. disagreements between these two authors were resolved through a discussion with the third author. the quality assessment of the included studies was investigated using the quality assessment of diagnostic accuracy studies (quadas)-2 tool. 2.4. statistical analysis statistical analysis was performed using meta-disc software version 1.4. heterogeneity between the included studies was assessed using i2. dersimonian-laird pooling method was used to estimate sensitivity, specificity, positive likelihood ratio (plr), negative likelihood ratio (nlr), diagnostic odds ratio (dor), and accuracy (summery receiver operating characteristic (sroc) curve). begg’s test and funnel plot were used to investigate publication bias. evaluation of the publication bias was carried out using stata statistical software package (stata corp., college station, tx, usa) (version 17.0). 3. results 3.1. study selection the systematic search identified a total of 245 studies, 58 of which were duplicates. we, then excluded 142 studies by screening their titles and abstracts. after reviewing the full texts and data integrity of the studies according to inclusion and exclusion criteria, 39 studies were excluded. finally, 18 studies were included in this meta-analysis. the prisma flow diagram of the studies during retrieval process and reasons for exclusion are illustrated in figure 1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e30 table 1: characteristics of the studies included in meta-analysis first author year country sample size study design gold standard tp fp fn tn sensitivity (%) specificity (%) sims et al. (17) 2020 australia 149 retrospective radiography 17 68 7 57 71 46 mohamed et al. (9) 2020 ireland 110 prospective radiography 12 60 0 38 100 39 shams vahdati et al. (18) 2019 iran 220 prospective radiography 164 44 0 12 100 21 cheung et al. (19) 2013 netherland 90 prospective radiography 6 64 1 19 86 23 beutel et al. (10) 2012 united states 260 retrospective radiography 41 128 0 91 100 42 konan et al. (20) 2012 england 106 prospective radiography 6 73 0 27 100 27 jalili et al. (21) 2010 iran 283 prospective radiography 21 146 1 115 95 44 atkinson et al. (14) 2004 england 72 prospective radiography 7 30 0 35 100 54 kec et al. (22) 2003 united states 85 prospective radiography 10 67 0 8 100 11 matteucci et al. (23) 2003 united states 134 prospective radiography 4 50 0 80 100 62 ketelslegers et al. (12) 2002 belgium 77 prospective radiography 12 37 0 28 100 43 szucs et al. (24) 2001 united states 96 prospective radiography 8 47 0 41 100 47 emparanza et al. (11) 2001 spain 1522 prospective radiography 89 688 0 745 100 52 tigges et al. (25) 1999 united sates 378 prospective radiography 42 271 1 64 98 19 seaberg et al. (8) 1998 united states 750 prospective radiography 84 487 3 176 97 27 stiell et al. (a) (1) 1997 canada 987 prospective radiography 58 483 0 446 100 48 richman et al. (26) 1997 united states 287 prospective radiography 22 143 4 118 85 45 stiell et al. (b) (6) 1996 canada 1096 prospective radiography 63 522 0 511 100 49 tp: true positive; fp: false positive; fn: false negative; tn: true negative. table 2: quality assessment of the included studies using quadas-2 tool study risk of bias applicability concerns patient selection index test reference standard flow and timing patient selection index test reference standard sims et al. (17) ? ? mohamed et al. (9) ? ? shams vahdati et al. (18) ? cheung et al. (19) beutel et al. (10) konan et al. (20) ? ? jalili et al. (21) ? atkinson et al. (14) kec et al. (22) matteucci et al. (23) ketelslegers et al. (12) ? szucs et al. (24) emparanza et al. (11) ? tigges et al. (25) seaberg et al. (8) stiell et al. (a) (1) § richman et al. (26) stiell et al. (b) (6) : low risk; §: high risk; ?: unclear risk. quadas: quality assessment of diagnostic accuracy studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 4 3.2. study characteristics finally, 18 eligible studies involving a total of 6702 patients with knee injury were included from different geographical regions. in all included studies, radiography was used as a gold standard for diagnosis of fracture. the diagnostic sensitivity ranged from 71% to 100%, while the diagnostic specificity was 11% to 62%. all included studies were published in english. the main characteristics of the included studies are provided in table 1. 3.3. quality assessment and risk of bias quality assessment of the included studies was performed using quadas-2 tool. the included studies had a low risk of bias and moderate to high quality. table 2 shows the results of quality assessment in detail. evaluation of publication bias using begg’s test (p=1) showed no significant publication bias. furthermore, investigation of publication bias using funnel plot revealed the same result (figure 2). 3.4. diagnostic accuracy of okr the heterogeneity was found to be significant for the pooled analysis of sensitivity (p=0.00, i2=70.9), specificity (p=0.00, i2=94.9%), plr (p=0.00, i2=94.5%), nlr (p=0.00, i2=68.1%), and dor (p=0.001, i2=57.6%). therefore, these parameters were analyzed using random-effects model. the metaanalysis of the 18 included studies showed that the pooled sensitivity and specificity of okr for diagnosis of fractures were 0.98 (95% ci: 0.96-0.99) and 0.43 (95% ci: 0.42-0.45), respectively (figure 3 and figure 4). the pooled plr and nlr were 1.56 (95% ci: 1.39-1.75) and 0.12 (95% ci: 0.05-0.26), respectively (figure 5 and figure 6). furthermore, the diagnostic odds ratio of okr was 13.02 (95% ci: 5.99-28.32) (figure 7). the area under curve (auc) of the hierarchical summary receiver operating characteristic (hsroc) curve was 0.54, indicating that the accuracy of okr for diagnosis of fractures in patients with knee trauma is 54% (figure 8). evaluation of threshold effect using spearman correlation revealed that there is no significant correlation between the sensitivity and specificity (r= 0.09, p=0.69). 4. discussion in this systematic review and meta-analysis of 18 studies investigating 6702 adult patients from nine countries, we demonstrated that the pooled sensitivity and specificity were 98% and 43% for okr. these findings reveal that the sensitivity is high enough to be applied to rule out fractures in patients with knee trauma in emergency departments and it has an adequate specificity. the pooled plr of 1.56 (95% ci, 1.39–1.75) and nlr of 0.12 (95% ci, 0.05–0.26) suggest that the odds of having a knee fracture in radiography increases by about 150% with a positive okr, whereas the odds is reduced by 99.88% with a negative okr. in a similar meta-analysis, bachman et al. (13) investigated the sensitivity, specificity, and nlr of okr for diagnosis of knee trauma using 6 studies involving 4249 patients. their analysis showed that the sensitivity and specificity of okr were 98.5% and 48.6%, respectively. furthermore, they found that nlr of okr is 0.05. although their sensitivity was similar to ours, their specificity was higher than the specificity that we found and their nlr was lower than what our analysis showed. these differences can be partially clarified by difference in the number of studies included in the meta-analysis. we included 18 studies, while they assessed 6 studies in their meta-analysis. in a study by atkinson et al. (14) the sensitivity and specificity of okr for diagnosis of fractures were 1 (95% ci: 0.63-1) and 0.53 (0.41-0.65), respectively. these findings reveal the importance of the referrer being aware of the okr. moreover, accumulating lines of evidence have recently proposed that the main barriers to okr usage were attributed to patients, and systematic and legal concerns rather than the efficacy of okr. therefore, in addition to increasing knowledge of evaluating doctors regarding okr, addressing systematic and legal barriers is crucial to improve adherence to this rule (10). okr was designed to estimate the probability of fracture and aid physicians in deciding on the requirement of requesting radiography in the assessment of trauma. the designers of knee rules considered a sensitivity of about 100% in diagnosing fractures to reduce unnecessary radiographs. however, the data regarding rate of reduction in unnecessary radiography were limited in previous studies and could not be pooled in our meta-analysis. additionally, we could not analyze data of time spent in emergency departments and direct and indirect costs saved due to reducing unnecessary radiography. a systematic review and meta-analysis of observational studies was carried out by vijayasankar et al. (15) to assess the diagnostic accuracy of okr in children. they identified three eligible studies involving 1130 subjects for inclusion in metaanalysis. the analysis revealed that the pooled sensitivity, specificity, plr, and nlr were 0.99 (95% ci: 0.94-0.99), 0.46 (95% ci: 0.43-0.49), 1.94 (95% ci: 1.60-2.36), and 0.07 (95% ci: 0.02-0.29), respectively. these findings show that sensitivity and specificity of okr in children were higher than adults. although the findings across these three studies were consistent, their quality was thought to be low, with little blinding, which affects the reliability of the meta-analysis. in another meta-analysis by sims et al. (16), the results of eight studies were pooled to indicate the diagnostic characteristics of okr for diagnosis of knee fractures. their pooled sensitivity and specificity of okr were higher than those we found in our meta-analysis. these differences may be clarified by considerable difference in the number of included studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e30 patients’ point of view and request may affect the efficacy of okr for reduction of unnecessary radiographs in clinical practice. some cases with knee trauma may request to be evaluated by radiography when they are evaluated in emergency department since they believe that an appropriate evaluation must include imaging. therefore, in addition to introduction of a rule to evaluating physicians, education of the patients is also needed to reduce frequency of unnecessary radiographs. our evaluation of the included studies indicates some limitations as most of them did not report need for further evaluation for patients without definite fracture in radiography and they did not investigate economic effects of the use of okr in emergency departments. 5. limitations despite valuable findings regarding pooled accuracy parameters of okr for diagnosis of knee fractures in adults, this meta-analysis faced several limitations: evaluation of the heterogeneity using i2 revealed significant heterogeneity, particularly for specificity (i2=94.9%), which may be due to the threshold effect where different cut-offs are applied. however, since assessment of threshold effect using spearman correlation showed that there was no significant correlation between sensitivity and specificity, it seems that the detected heterogeneity may only slightly affect the findings. another limitation of our meta-analysis is that we did not investigate the accuracy of okr for children. furthermore, evaluation of the economic effects of okr and needs for further imaging in patients with no definite fracture were not carried out in our study. few studies used both radiography and follow-up as reference standard for diagnosis of fracture suggesting risk of flow and timing bias in the results of quadas-2 evaluation. 6. conclusion this systematic review and meta-analysis of 6702 adult patients with acute knee trauma indicates that okr has a high diagnostic performance for diagnosis of fracture, with a pooled sensitivity of 98% and a pooled specificity of 43%. although our findings suggest applying the okr as a sensitive rule in emergency departments, its widespread application still has some limitations. these results propose potential effects of okr on reduction of unnecessary radiography, time spent in emergency departments, and direct and indirect costs, which should be confirmed using high-quality, large-scale, multicenter studies in the future. 7. declarations 7.1. acknowledgments the authors thank all those who contributed to this study. 7.2. conflict of interest none. 7.3. fundings and supports this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. authors’ contribution all authors contributed to study design, data collection, writing the draft of the study and reading and approving the final version. 7.5. data availability not applicable. 7.6. human and animal rights statement this meta-analysis does not contain any investigations with human or animal subjects. references 1. stiell ig, wells ga, hoag rh, sivilotti ml, cacciotti tf, verbeek pr, et al. implementation of the ottawa knee rule for the use of radiography in acute knee injuries. jama. 1997;278(23):2075-9. 2. stiell ig, greenberg gh, wells ga, mcknight rd, cwinn aa, cacciotti t, et al. derivation of a decision rule for the use of radiography 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2002;12(5):1218-20. 13. bachmann lm, haberzeth s, steurer j, ter riet g. the accuracy of the ottawa knee rule to rule out knee fractures: a systematic review. ann intern med. 2004;140(2):121-4. 14. atkinson p, boyle a, chisholm e. x-ray requesting patterns before and after introduction of the ottawa knee rules in a uk emergency department. eur j emerg med. 2004;11(4):204-7. 15. vijayasankar d, boyle a, atkinson p. can the ottawa knee rule be applied to children? a systematic review and meta-analysis of observational studies. emerg med j. 2009;26(4):250-3. 16. sims ji, chau mt, davies jr. diagnostic accuracy of the ottawa knee rule in adult acute knee injuries: a systematic review and meta-analysis. eur radiol. 2020;30:443846. 17. sims ji, chau m, davies j. validation of the ottawa knee rule in adults: a single centre study. j med radiat sci. 2020;67(3):193-8. 18. vahdati ss, ala a, samani z, ahari sg, mirza-aghazadehattari m. screening of trauma patients in need of knee radiography by triage nurses and using ottawa knee rule; a letter to editor. arch acad emerg med. 2019;7(1):e57. 19. cheung tc, tank y, breederveld rs, tuinebreijer we, de lange-de klerk es, derksen rj. diagnostic accuracy and reproducibility of the ottawa knee rule vs the pittsburgh decision rule. am j emerg med. 2013;31(4):641-5. 20. konan s, zang t, tamimi n, haddad f. can the ottawa and pittsburgh rules reduce requests for radiography in patients referred to acute knee clinics? ann r coll surg engl. 2013;95(3):188-91. 21. jalili m, gharebaghi h. validation of the ottawa knee rule in iran: a prospective study. emerg med j. 2010;27(11):849-51. 22. kec rm, richman pb, szucs pa, mandell m, eskin b. can emergency department triage nurses appropriately utilize the ottawa knee rules to order radiographs? an implementation trial. acad emerg med. 2003;10(2):146-50. 23. matteucci mj, roos ja. ottawa knee rule: a comparison of physician and triage-nurse utilization of a decision rule for knee injury radiography. j emerg med. 2003;24(2):147-50. 24. szucs pa, richman pb, mandell m. triage nurse application of the ottawa knee rule. acad emerg med. 2001;8(2):112-6. 25. tigges s, pitts s, mukundan jr s, morrison d, olson m, shahriara a. external validation of the ottawa knee rules in an urban trauma center in the united states. ajr am j roentgenol. 1999;172(4):1069-71. 26. richman pb, mccuskey cf, nashed a, fuchs s, petrik r, imperato m, et al. performance of two clinical decision rules for knee radiography. j emerg med. 1997;15(4):45963. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e30 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flowchart of the literature search and selection of studies that reported accuracy of ottawa knee rule (okr) for diagnosis of fracture in patients with knee injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 8 figure 2: funnel plot of publication bias on the pooled diagnostic odds ratio (dor). ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e30 figure 3: forest plot of the pooled sensitivity of ottawa knee rule (okr) for diagnosis of fracture in patients with knee trauma. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 10 figure 4: forest plot of the pooled specificity of ottawa knee rule (okr) for diagnosis of fracture in patients with knee trauma. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e30 figure 5: forest plot of the pooled positive likelihood ratio (plr) of ottawa knee rule (okr) for diagnosis of fracture in patients with knee trauma. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 12 figure 6: forest plot of the pooled negative likelihood ratio (nlr) of ottawa knee rule (okr) for diagnosis of fracture in patients with knee trauma. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e30 figure 7: forest plot of the pooled diagnostic odds ratio (dor) of ottawa knee rule (okr) for diagnosis of fracture in patients with knee trauma. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index s-m. kazemi et al. 14 figure 8: hierarchical summary receiver-operating characteristic (hsroc) curve indicating accuracy of okr for diagnosis of fracture in patients with knee trauma. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2022; 10(1): e70 or i g i n a l re s e a rc h the effect of gracilaria corticata and scenedesmus acuminates extract mixture on the healing of wounds contaminated with staphylococcus in the rat model hooman akasheh1, alireza jahandideh1∗, amireghbal khajerahimi1, shapour kakoolaki3, saeed hesaraki2 1. department of clinical science, science and research branch, islamic azad university, tehran, iran. 2. department of pathobiology, science and research branch, islamic azad university, tehran, iran. 3. iranian fisheries science research institute, agriculture research education and extension organization (areeo), tehran, iran received: june 2022; accepted: july 2022; published online: 29 august 2022 abstract: introduction: wound healing processes are dependent on the severity of the trauma, invasion of opportunistic microorganisms, and inflammatory, immunological, and metabolic responses. we tried to show the ability of algae to inhibit wound infection, which can lead to proper wound healing. methods: eighty rats were housed according to laboratory animal care protocols and divided into four groups at each operating time. group i consisted of the non-treated animals. group ii was treated with 25% zinc oxide as a choice treatment. in the treated groups 3 and 4, an equal ratio of gracilaria corticata and scenedesmus acuminate marine algae (mixed algae) was applied as 3% and 7% ointment pomade. percentage of wound closure, number of bacteria in the wound surface, angiogenesis (vascular endothelial growth factor; vegf), the number of macrophages, collagen production level and transforming growth factor-beta (tgfβ), epithelialization, and fibrosis were evaluated. results: applying mixed algae extract 7% and zinc oxide 25% could result in a mild improvement in wound closure (df: 9, 48; f=5.97; p<0.0001). in addition, mixed algae 3%, mixed algae 7% and zinc oxide could reduce the rate of bacterial growth compared to non-treated animals (df: 3, 16; f=5.74; p=0.0007). however, these improvements do not seem to be clinically significant. induction of angiogenesis, increase in macrophage infiltration rate, and expression of tgfβ are possible underlying mechanisms of mixed algae in accelerating wound healing process. conclusion: the result showed that the administration of 3% and 7% mixed algae could mildly accelerate the wound healing process in a rat model of pelleted skin wound. however, it seems that its effect is not clinically significant compared to non-treated and zinc oxide treated animals. keywords: gracilaria; scenedesmus; staphylococcus aureus; wound healing; cd68 protein, rat; transforming growth factor beta; vascular endothelial growth factor a, rat cite this article as: akasheh h, jahandideh a, khajerahimi a, kakoolaki s, hesaraki s. the effect of gracilaria corticata and scenedesmus acuminates extract mixture on the healing of wounds contaminated with staphylococcus in the rat model . arch acad emerg med. 2022; 10(1): e70. https://doi.org/10.22037/aaem.v10i1.1686. 1. introduction wounds are a common problem of the skin. wounds occur due to trauma injuries, leading to an opening of the epidermis and underlying dermis. to return the troubled utilitarian state of the skin and interrupted epithelial and connective tissue continuity back to normal state, the healing of the ∗corresponding author: alireza jahandideh; department of clinical science, faculty of specialized veterinary science, science and research branch, islamic azad university, tehran, iran. email: dr.jahandideh@gmail.com, tel: 00989122476037, orcid: https://orcid.org/0000-0002-4212-6416. wound is important. wound healing processes are dependent on the severity of the trauma, invasion of opportunistic microorganisms, and inflammatory, immunological, and metabolic responses. the healing process is dependent on the type of the infiltrated leukocytes, activated mast cells, the content of the extracellular matrix, and various inflammatory or regulatory mediators, which contribute to restoring tissue integrity (1, 2). resistance to routine antibiotics used to treat wound infections is a harmful consequence. various types of antibiotics and the pathogens that infect the wound have developed more resistance against the routine antibiotics (3). staphylothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akasheh et al. 2 coccus aureus is a pathogenic bacterium that can infect the wound. the methicillin-resistant form of staphylococcus aureus can lead to treatment failure. the formation of biofilm is a factor that reduces antibiotic penetration (4). investigation of various traditional plant extracts has demonstrated their healing ability for skin wounds. these pharmaceutical extracts promote wound healing by inducing epithelial cell and fibroblast proliferation, leukocyte migration, and cell differentiation and have additional advantages, such as antimicrobial activity against the infection (5). the use of medicinal plant extract remedies to promote effective wound healing develops every day. many years before, investigators found that plant extracts have antimicrobial and wound healing properties, which may be used as an efficient, safe, and economic wound healing medicine to heal infected injuries. scenedesmus acuminatus, a colonial green alga, is usually seen floating on the river. unlike colonial green algae, scenedesmus makes only four-cell chains. the ends of the colony possess small oil vacuoles, which enable them to float in the water. scenedesmus acuminatus contains many antioxidants, including glutathione (gsh), tocopherols, flavonoids, ascorbate, and polyphenols. moreover, it also has many antioxidant enzymes, including glutathione reductase (gr), glutathione s transferase (gst), superoxide dismutase (sod), ascorbate peroxidase (apx), and peroxidase (6). some previous studies demonstrated that the fatty acid methyl esters (fame) or pigment extract obtained from scenedesmus exhibit anti-staphylococcus aureus and antifungal activity. these fatty acids from scenedesmus can break the protective mechanisms of bacteria against antibiotics (7). a bio-content analysis of the gracilaria corticata revealed that tannins were the most abundant compounds. the cytotoxic results showed that this algae species could inhibit the growth of human colorectal adenocarcinoma cell line. thus, this marine red algae could be a reservoir of antitumor food additives for cancer prevention (8). algal extracts can be excellent wound dressings because of their excellent biocompatibility and biodegradability. they help in the healing process with two properties. they can cover the wound to prevent drying and infection. in addition, they can act as a vehicle for delivering various drugs to the wound site. marine algae could operate as biochemical and organic antioxidants (9). the ethyl acetate extract of gracilaria corticata has an inhibitory activity on acetylcholinesterase in zebrafish (10). some studies proved that alginates could treat gastritis and gastric ulcers (11). the evaluation of algae as an antibiotic is undertaken in past years (12). this antibacterial, antioxidant, and phenolic activity is reported in the scenedesmus quadricauda (13, 14). however, the results are scarce and contradicting (15). therefore, we tried to investigate the ability of algae to inhibition wound infection, which can lead to proper healing of skin injuries. 2. methods 2.1. preparation of the algae extract gracilaria corticata and scenedesmus acaminatus platensis were extracted from the persian gulf at 50-100 cm depth. after washing the algae to remove epiphytes and pollution, we dehydrated them with tissue paper and took them out to dry in the sun. we milled dried specimens with a pulverizer and produced the alcoholic extract using the soxhlet machine. a vacuum distiller evaporated the juices to remove the solvent. then we preserved them in the refrigerator at 4°c. we mixed the extracts of gracilaria corticata and scenedesmus acaminatus platensis equally and used them in pharmacological investigations (9). 2.2. experimental animals eighty 200±30 gr wistar albino rats of both sexes were entered in the experiment. the rats were kept in optimized laboratory conditions (22-25 °c, humidity=60±5 percentage, and 15 h light) with free access to food and water. they were kept in similar cages and randomly selected for model induction and outcome assessment using a random numbers table. animals were randomly divided into four groups (n=20 per group) and desired outcomes were assessed on days 3, 7, 14 and 21 after wound induction. five animals were assessed in each follow-up time point. the experimental groups are introduced in table 1. all included animals survived during the study (mortality rate of zero). this experiment was done with the approval of the local ethic committee, under the code number 97001781 (ir.ajaums.rec.1400.313). 2.3. wound induction model and treatments induction of wound was done in blinded manner, in which the caregiver was not aware of the experimental groups. clipping and shaving were performed on the operation site, and a 1.5×1.5 cm full-thickness square wound was made. after creating wounds, we contaminated all back wounds of the rats with 50 µl of 2×108 cfu/ml staphylococcus-containing suspension. ointments including zinc oxide, mixed algae 3% and mixed algae 7% were applied to the wound area from the day after wound induction once daily for 21 days. 2.4. outcomes all outcome measurements were performed on days 3, 7, 14, and 21 after wound induction by an investigator who was blinded to the animal groups. in addition, animals were randomly selected for outcome assessments at each time-point. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2022; 10(1): e70 2.5. wound size on day 1, before administration of treatments, the wound size was recorded through measurement of greatest width and length. length and width were multiplied and square area was calculated. the wound size was assessed using the same method on days 3, 7, 14, and 21 after wound induction. the wound size in specific days was calculated as st/s0×100, where s0 is the wound area at the time before treatment and st is the wound area at the time t and reported as percentage. clinically significant improvement was defined as at least 50% reduction in wound size compared to baseline. 2.6. number of wound bacterial colonies we put a swab on the wound and then placed it in 1 ml of sterile normal saline. the swab discharged the staphylococcus into the fluid. we diluted the liquid 10-fold with sterile normal saline. then, 5 µl of the sample was added to a mueller-hinton agar plate and incubated for 24 hours. finally, bacterial colonies were counted using an automatic colony counter (scan 1200 inter-science company, france). the number of bacterial colonies was assessed on days 1, 3 and 7. 2.7. histopathological evaluation of the wound healing the wound area was cut around and gathered. the tissues were fixed in 10% formaldehyde for 36 hours after euthanasia of rats using overdosed anesthetic materials. after paraffin embedding, 5 µm sections were prepared using a microtome. the samples were stained using hematoxylin/eosin and masson trichrome stain. the samples were analyzed by a pathologist who was blinded to the animals’ groups. the histological grading was made based on angiogenesis, the number of macrophages, collagen level, epithelization, and fibrosis. each factor was given a score of 0-3 for grading. the absence of a phenomenon was scored 0; a mild presentation was scored 1, the moderate one was scored 2, and the severe one was scored 3 (16). 2.8. immunohistochemical evaluation all materials were purchased from sigma/aldrich company (germany). after fixing the samples and embedding them in paraffin, we cut them into 5-µm tissue sections. the endogenous peroxidase was quenched through exposure to 3% hydrogen peroxide. the excess antigens were blocked after dropping 1% bovine serum albumin on the sample. we incubated the slides with a primary antibody against transforming growth factor-beta (tgfβ), vascular endothelial growth factor (vegf), or cd68 at 1:400 dilutions overnight. after washing the tissues, the slides were incubated with 1:400 dilutions of goat anti-mouse igg antibody (abcam) for 1 table 1: experimental groups experimental group intervention non-treated wound induction without any treatment zinc oxide wound induction + treated with 25% zinc oxide mixed alga 3% wound induction + treated with gracilaria corticata mixed with scenedesmus acuminate marine algae extract 3% mixed alga 7% wound induction + treated with gracilaria corticata mixed with scenedesmus acuminate marine algae extract 7% hour at room temperature. the slides were treated with diaminobenzidine (dab) for 5 minutes after washing. counterstaining with hematoxylin was operated. the tissue slides were put in alcohol and then xylene. then they were mounted on a mounting medium, and were studied to evaluate the rate of gene expressions. 2.9. statistical analysis data are presented as mean ± standard deviation. twoway repeated measures anova and bonferroni post hoc test were used to assess the mean difference of normal quantitative variables across different time-points. time trend of histopathological scores’ (ordinal variables) changes was evaluated using friedman test. finally for assessment of clinically significant changes we used jonckheere–terpstra test for trend. in this test, at least 50% decrease in wound area or wound bacterial colony was considered success rate. the p-values less than 0.05 were considered significant. 3. results 3.1. percent of wound closure two-way repeated measures anova revealed that the wound closure was significantly different among studied groups (df: 9, 48; f=5.97; p<0.0001). three-day follow ups showed that administration of zinc oxide ointment can accelerate wound closure compared to non-treated group (p=0.029). seven days after wound induction, wound size in zinc oxide(p=0.003) and mixed algae 7%-treated (p=0.0003) groups had significantly decreased compared to non-treated animals. while in 14-day follow-up, wound size had significantly decreased only in mixed algae 7% group (p=0.014) compared to non-treated group. in contrast, there was no significant difference between any of the groups on the 21st day (figure 1). to assess clinically significant improvement, we compared the number of animals with at least 50% decrease in wound size between experimental groups. the results showed that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akasheh et al. 4 figure 1: the percentages and success rates of wound closure and the number of wound bacterial colonies. on the 3rd and 7th days post-injury there were no rats with at least 50% decrease in wound size in non-treated and mixed algae 3% groups. while, 50% decrease in wound size was observed in 60% and 80% of animals in the zinc oxide and mixed algae 7% groups seven days post-injury. notably, all animals reached at least 50% decrease in wound size by day 14. the non-parametric test for trend showed that clinically significant improvement (at least 50% decrease in wound size) is similar among studied groups (p=0.066) (figure 1). 3.2. number of bacterial colonies in wound culture mixed algae 3%, mixed algae 7% and zinc oxide could reduce the rate of bacterial growth compared non-treated animals (df: 3, 16; f=5.74; p=0.0007). on day 3, the efficacy of mixed algae 3% (p>0.999) and mixed algae 7% (p=0.257) was similar to zinc oxide. the inhibitory effect of mixed algae 7% was more predominant than zinc oxide (p<0.0001) and mixed algae 3% (p<0.001) seven days after the initiation of treatment (figure 1). 50% decrease in the number bacterial colonies in wound culture was observed in all treated animals on days 3 and 7, while there were no animals with 50% decrease in the number of bacterial colonies in wound culture in nontreated groups. the non-parametric test for trend showed that success rate was significantly higher in zinc oxideand mixed algae-treated animals compared to non-treated animals (p=0.0007) (figure 1). 3.3. histopathological results angiogenesis qualitative histopathological assessment showed a nonsignificant increase in angioblasts in the zinc oxide and mixed algae 3%-treated groups compared to non-treated animals on days 3, 7, 14 and 21. proliferating angioblasts formed numerous new blood vessels in the granulation tissue in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2022; 10(1): e70 figure 2: histological assessment of infected skin wounds of rats in different treatment groups on day 3 (a, b, c and d), day 7 (e, f, g and h), day 14 (i, j, k and l) and day 21 (m, n, o and p) post-surgery (trichrome ×100). star: wound surface; black arrow: collagen fibers; yellow arrow: new blood vessels, up-down arrow: epithelium. error bar represents 200 µm. non-treated: a, e, i and m; zinc oxide: b, f, j and n; mixed algae 3%: c, g, k and o; mixed algae 7%: d, h, l and p. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akasheh et al. 6 figure 2: histological assessment of infected skin wounds of rats in different treatment groups on day 3 (a, b, c and d), day 7 (e, f, g and h), day 14 (i, j, k and l) and day 21 (m, n, o and p) post-surgery (trichrome ×100). star: wound surface; black arrow: collagen fibers; yellow arrow: new blood vessels, up-down arrow: epithelium. error bar represents 200 µm. non-treated: a, e, i and m; zinc oxide: b, f, j and n; mixed algae 3%: c, g, k and o; mixed algae 7%: d, h, l and p. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2022; 10(1): e70 mixed algae 7%-treated animals on day 3, day 7, and day 14. finally, the number of blood vessels were reduced in all groups 21 days post-operation (figure 2). quantitative analysis based on friedman test showed that zinc oxide and mixed algae 3% did not have a significant effect on angiogenesis score in any of the time points (p>0.05). while, mixed algae 7% increased angiogenesis score 3 days (p=0.028) and 7 days (p=0.002) after wound induction compared to non-treated animals. angiogenesis score on day 21 did not significantly differ among study groups (p>0.05; figure 2). immuno-histochemical evaluation showed that vegf expression was changed in treated groups (df: 9, 48; f=43.26; p<0.0001). post hoc analysis revealed that mixed algae 7% could increase the expression of vegf from day 3 (p=0.041). on day 7, zinc oxide (p=0.006), mixed algae 3% (p=0.009), and mixed algae 7% (p<0.0001) could increase the level of vegf. on day 14, only zinc oxide increased vegf expression (p=0.038). interestingly, on day 21, vegf expression in zinc oxide (p=0.006) and mixed algae (p=0.026) groups was lower than the non-treated group (figure 2). fibrosis qualitative report by a pathologist, few fibroblasts were observed in the wound area and no notable starting of fibrosis was observed in any of the groups on day 3. the fibroplasia of the mixed algae 7% group was slightly higher than the other groups on day 7. although the fibrosis had increased 14 days and 21 days post-injury, there were no significant differences between groups. quantitative analysis based on friedman test showed that fibrosis score was not significantly different between experimental groups in any of the time points (p>0.05) (figure 2). collagen synthesis qualitative assessment showed that mixed algae administration in both doses led to production of fine collagen bundles in the primary granulation tissue compared with the nontreated group on day 3 and day 7. identical collagen synthesis was extensively observed on day 14 and day 21 in all groups. quantitative analysis based on friedman test showed that collogen synthesis score was not significantly different between experimental groups in all time points (p>0.05) (figure 2). epithelial regeneration no notable epithelial regeneration was observed on day 3. seven days after treatment, the epithelial formation started with no significant difference between the groups. on day 21, epithelialization was hyperplastic in both non-treated and 7% mixed algae groups. the highest epithelialization rate was observed in non-treated animals (figure 2). friedman test showed that epithelization was not significantly different between experimental groups in all time points (p>0.05) (figure 2). macrophage infiltration the highest rate of infiltration of macrophages was seen in the mixed algae 7%-treated group 3 days post-wound induction. seven days after wound induction, the number of macrophages in the mixed algae-treated groups was higher than in the non-treated group. in addition, the number of macrophages in the 7% mixed algae-treated groups was higher than non-treated and group 3% mixed algae-treated groups 14-day post operation. finally, macrophages were reduced in all groups 21 days after induction of wounds. however, the number of macrophages in the non-treated animals were much higher than in other groups (figure 2). friedman test revealed that macrophage infiltration score in zinc oxide (p=0.008) and mixed algae 7% (p=0.018) were significantly higher than non-treated animals. while on day 21, this score was significantly higher in non-treated animals (p for zinc oxide=0.026; p for algae 7%=0.020) (figure 2). immunohistochemistry assay depicted that the percentage of macrophages (cd68-positive cells) in the granulation tissue was significantly different between studied groups (df: 9, 48; f=32.53; p<0.0001). multiple comparison showed that macrophage infiltration in mixed algae 3% (p=0.0006) was significantly higher than the non-treated group on day 3. on day 7, the macrophage infiltration rate significantly decreased in mixed algae 3% (p=0.001) and its level remained low until the end of follow-up. on day 14, the macrophage infiltration rate had increased in zinc oxide (p<0.0001) and mixed algae 7% (p=0.001) groups, while on day 21 the macrophage infiltration rate was only high in zinc oxide (p=0.004) group (figure 2). tgfβ expression immunohistochemistry assay depicted that the expression of tgfβ was significantly different between studied groups (df: 9, 48; f=49.50; p<0.0001). multiple comparison showed that tgfβ in mixed algae 7% (p=0.014) group was significantly higher than non-treated group on day 3. on day 7, tgfβ expression was significantly higher in mixed algae 3% (p=0.0002) group. on day 14, tgfβ expression had increased in zinc oxide (p=0.043) and mixed algae 3% (p<0.0001) groups. while on day 21, the level of tgfβ expression was not significantly different between treated groups compared to non-treated animals (p>0.05) (figure 2). 4. discussion the results showed that the administration of mixed algae 3% and 7% could mildly accelerate the wound healing process in a rat model of pelleted skin wound. however, it seems that this effect is not clinically significant compared to nontreated and zinc oxide-treated animals. in addition, mixed algae have a possible anti-bacterial activity. although, the effect was clinically significant compared to non-treated anithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. akasheh et al. 8 mals, its antibacterial activity was the same as zinc oxide. induction of angiogenesis, increase in macrophage infiltration rate, and expression of tgfβ are possible underlying mechanisms of mixed algae in accelerating the wound healing process. the gracilaria genus is an economical marine seaweed, because it is a worldwide source of agar. this seaweed grows throughout the tropical areas. extraction of seaweed is typically accomplished by solvent extraction processes using alcohol and acetone and through water steam or distillation (14). some studies showed that the antioxidant properties of the calcium alginate of brown seaweeds could heal and prevent the toxic effects of ccl4-induced hepatotoxic injury in rats (17). some studies showed that microalgae contain metabolites that are effective against the development and growth of some pathogenic gram-negative and gram-positive bacteria. the phenolic compounds are a significant contributor to the antioxidant properties of the microalgae (8). after inducing a wound, tgfβ is secreted by macrophages, keratinocytes, and platelets. tgfβ is necessary for starting granulation, tissue formation, and fibrosis. in addition, tgfβ is indispensable for cell migration during wound repair (2). in addition, vegf stimulates multiple components of the angiogenic cascade. when capillary growth is maximal, it is released early in healing (18). the outputs of the present study may provide a vital insight into the field of natural drug discovery. a study in 2014 showed that the marine algae gracilaria corticata and spirulina platensis were the best biosources of active substances such as various phytochemicals, antioxidants, and antibiotics (7, 8). some studies revealed that topical application of algae extracts could increase wound contraction and reduce wound closure time (19, 20). the decrease in wound size was significant in animals treated with gracilaria compared to the control group until the 20th day. the extract induced whole healing compared to usual drugs (20). however, our results showed that, although, the effect of mixed algae on wound closure was statistically significant compare to non-treated animals, its effect was not clinically significant. this difference implies the importance of assessment of clinical significance level in animal studies. in this study, on day seven post-surgery, mixed algae at a concentration of 7% showed inhibitory effects on bacterial growth. sargassum illicifolium components showed medium inhibitory potency on staphylococcus aureus, and more inhibitory strength against pseudomonas aeruginosa. it could increase fibroblast proliferation and migration (21). adding a trace amount of ag to red algae can produce a spherical shape with hydrodynamic nanoparticles. this shape and size of synthesized ag carrier algae showed high antibacterial activity against bacteria, especially gram-negative ones. nineteen species of gracilaria sp. can inhibit the growth of many bacteria, viruses, and fungi. they can also reduce inflammatory cascades (22). some studies on improving angiogenesis of the skin wounds using algae extract showed that the wound healing activity of gracilaria extract in rats at the concentration of 200 mg/kg was better than that of standard ointment on the sixth day of the investigation (22). consistently, our results also showed that the mixed algae 7% group had the most blood vessels and highest induction of angiogenesis. also, in the last days of repair, which required less angiogenesis, the number of vessels was reduced. one of the critical factors in wound repair is collagen production, which did not change significantly in different groups. macrophages are identified as brown against a pale ground background (16). the presence of macrophages on days 3 and 7 after surgery is a hallmark for inducing proper repair because they help repair by secreting various repairing cytokines such as tgfβ and fibroblast growth factors. although tissue engineering offers unlimited possibilities for regenerative medicine, several problems limit its clinical application. insufficient oxygen delivery to 3d cultures is considered one of the most significant limitations for the practical application of tissue engineering in vitro (23). simultaneously, tissue regeneration relies on necessary nutrients and bioactive molecules to control critical biological processes (24). photosynthesis is the source of oxygen; thus, microalgae cab offers a new way to supply adequate oxygen for tissue engineering. photosynthetic microalgae chlamydomonas reinhardtii (c. reinhardtii) have been widely studied in tissue engineering in recent years. for example, hopfner et al. cultured c. reinhardtii in scaffolds for tissue repair. then the microalgae showed high biocompatibility and photosynthetic activity. in addition, c. reinhardtii could be cocultured with fibroblasts, reducing the hypoxia response of cells under hypoxic culture conditions. based on the in vitro studies, when the microalgae scaffold was transplanted into a mouse skin defect, it was found that the microalgae survived for at least five days in vivo, and chimeric tissues composed of algae and mouse cells were formed (25). on this basis, scaffolds constructed by genetically modified microalgae have also been developed, which can also deliver recombinant molecules for gene therapy and essential oxygen supply. chávez et al. created a genetically modified c. reinhardtii that constitutively secreted the human vascular endothelial growth factor vegf-165 (vegf) to the wound tissues in vivo (26). other algal scaffolds have also been applied in tissue engineering. for instance, chlorococcum littorale scaffolds could provide enough oxygen to sustain the survival of c2c12 or rat cardiac single-layer cell sheets (27). arthrospira scaffolds could improve the adherence and proliferation ability of mesenchymal stem cells from c57/b16n mice liver (28). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2022; 10(1): e70 5. conclusion the results showed that the administration of mixed algae 3% and 7% could mildly accelerate the wound healing process in a rat model of pelleted skin wound. however, it seems that this effect is not clinically significant compared to nontreated and zinc oxide-treated animals. in addition, mixed algae have a possible anti-bacterial activity. although, the effect was clinically significant compared to non-treated animals, its antibacterial activity was the same as zinc oxide. induction of angiogenesis, increase in macrophage infiltration rate, and expression of tgfβ are possible underlying mechanism of mixed algae in accelerating wound healing process. 6. declarations 6.1. acknowledgments here we owe it to ourselves to thank the staff of the laboratory and clinic of the islamic azad university, science and research branch. 6.2. the ethics code and irct number this experiment has received ethical approval under the code number 97001781(ir.ajaums.rec.1400.313). 6.3. conflict of interest no conflict of interest. references 1. enoch s, leaper dj. basic science of wound healing. surgery (oxford). 2008;26(2):31-7. 2. makrantonaki e, wlaschek m, scharffetter-kochanek k. pathogenesis of wound healing disorders in the 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2016;75:25-36. 27. haraguchi y, kagawa y, sakaguchi k, matsuura k, shimizu t, okano t. thicker three-dimensional tissue from a “symbiotic recycling system” combining mammalian cells and algae. sci rep. 2017;7(1):1-10. 28. steffens d, lersch m, rosa a, scher c, crestani t, morais m, et al. a new biomaterial of nanofibers with the microalga spirulinaas scaffolds to cultivate with stem cells for use in tissue engineering. j biomed nanotechnol. 2013;9(4):710-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 66 emergency (2014); 2 (2): 66-70 original research report of 121 cases of bell's palsy referred to the emergency department behzad zohrevandi, vahid monsef kasmaee*, payman asadi, hosna tajik road trauma research center, guilan university of medical sciences, rasht, iran abstract introduction: according to the high incidence of bell's palsy (ifp) and lack of clinical data regarding different aspects of disease, the present study investigated 121 iranian patients with peripheral facial paralysis referred to the emergency department. methods: in this retrospective study, all patients with peripheral facial paralysis, referred to the emergency department of poursina hospital, rasht, iran, from august 2012 to august 2013, were enrolled. for all patients with diagnosis of bell's palsy variables such as age, sex, occupation, clinical symptoms, comorbid disease, grade of paralysis, and the severity of the facial palsy were reviewed and analyzed using stata version 11.0. results: 121 patients with peripheral facial paralysis were assessed with a mean age of 47.14±18.45 years (52.9% male). the majority of patients were observed in the summer (37.2%) and autumn (33.1%) and the recurrence rate was 22.3%. the most common grades of nerve damage were iv and v based on house-brackman grading scale (47.1%). also, the most frequent signs and symptoms were ear pain (43.8%), taste disturbance (38.8%), hyperacusis (15.7%) and increased tearing (11.6%). there were not significant correlations between the severity of palsy with age (p= 0.08), recurrence rate (p=0.18), season (p=0.9), and comorbid disease including hypertension (p=0.18), diabetes (p=0.29), and hyperlipidemia (p=0.94). the patients with any of following symptoms such as ear pain (p<0.001), taste disturbance (p<0.001), increased tearing (p=0.03), and hyperacusis (p<0.001) have more severe palsy. conclusion: there was equal gender and occupational distribution, higher incidence in fourth decade of life, higher incidence in summer and autumn, higher grade of nerve damage (grade v and vi), and higher incidence of ear pain and taste disturbance in patients suffered from ifp. in addition, there was significant association between severity of nerve damage and presence of any simultaneous symptoms. key words: bell palsy; facial nerve diseases; paralysis; epidemiology; peripheral neuropathy cite this article as: zohrevandi b, monsef kasmaee v, asadi p, tajik h. report of 121 cases of bell's palsy referred to the emergency department. emergency. 2014;2(2):66-70. introduction:1 ell´s palsy, or idiopathic facial paralysis (ifp), is defined as an acute peripheral palsy of seventh cranial nerve. it is one of the most common neurological disorders which usually manifests with facial weakness, ear pain, taste disturbance, hyperacusis, and increased tearing (1). the worldwide incidence of ifp is 11 to 40 per 100,000 people annually (2, 3). its prevalence among males and females is more or less equal and its peak incidence is in the fourth decade of life (46). the occurrence of familial bell´s palsy is about 14% and its recurrent risk is about 10% (7). unilateral paralysis is the most common presentation of ifp occurs with the same frequency on the right and left sides of the face (4-6, 8). the most common causes of the abrupt onset of unilateral facial weakness are stroke and bell´s palsy (9). due to the close similarity between the symp *corresponding author: vahid monsef kasmaee; road trauma research center, guilan university of medical sciences, poursina hospital, rasht, iran. phone: +989113344071. fax: +981313238373 email: vmonsef@yahoo.com received: 2 march 2014; accepted: 13 may 2014 toms of ifp and cerebrovascular accident, it is essential for emergency physicians to differentiate them (10, 11). several risk factors can cause ifp including viral infection, vascular ischemia, autoimmune inflammatory disorders, age, hypertension, and heredity (11, 12). controversies exist regarding the incidence of ifp and its relation with potential risk factors (13-17). reports showed an increased incidence of ifp in the third and fourth decades of life and an increased rate of disease in colder months (autumn and winter) (15, 18). besides, the findings of another study demonstrated the increase in the incidence of the ifp in the spring (13). therefore, according to the high incidence of facial palsy and lack of clinical data regarding different aspects of disease, the present study investigated 121 iranian patients with peripheral facial paralysis referred to the emergency department. methods: a retrospective cross-sectional study was performed for patients with acute seventh nerve palsy referred to emergency department of poursina hospital, rasht, b this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 67 zohrevand et al iran, from august 2012 to august 2013. patients with facial palsy in both upper and lower parts of the face, examined by an emergency medicine specialist and then a neurologist, were included. patients with seventh nerve palsy without involving the upper part of the face were excluded. data collected from patients including gender, age, employment status, season of disease, affected side, clinical symptoms (such as severity of facial palsy, taste disturbance, ear pain and increased tearing), and comorbid disease (such as diabetes, hyperlipidemia, hypertension) were recorded in a specific datasheet. the clinical severity of the facial palsy was assessed using the housebrackman (hb) grading scale (19, 20). the study was approved by the ethical committee of gilan university of medical sciences. data were analyzed using stata version 11.0. mannwhitney u and chi-square tests were used to compare the results and find a correlation between ordinal and nominal variables, respectively. multinomial logistic regression was used to predict the probabilities of the possible differences among categories. effects of season, age, gender, comorbid disease, and clinical factors on severity of paralysis were investigated using generalized linear poisson model and results were expressed as adjusted rate ratio (rr) and 95% confidence interval (95% ci). p-value <0.05 was considered as significant. results: a total number of 121 patients with bell´s palsy were studied (52.9% cases were male). the mean age of patients was 47.14±18.45 years (range: 16-81). figure 1 shows the incidence rate of ifp in different age groups. the maximum incidence rate of ifp was in the fourth decade of patient’s life (27.3%, p<0.007). twenty-eight patients (23.1%) were self-employed and 14 (11.6%) ones farmers. figure 2 demonstrates the seasonal incidence of ifp. the seasonal incidence of disease was significantly higher in summer (37.2%, p<0.001) and autumn (33.1%, p=0.002). regarding the involved side, 63 patients suffered from ifp on the left side. ninety-four cases (77.7%) experienced ifp for the first time (22.3% recurrence rate). the most frequent simultaneous symptoms with facial palsy were ear pain (43.8%), taste disturbance (38.8%), hyperacusis (15.7%), and increased tearing (11.6%) (p<0.001) (table 1). figure 3 demonstrated the percentage of different grades of nerve palsy. the most frequent grade of nerve damage based on hb grading scale was v grade (28.1%, p=0.001). six (30%) men and 14 (70%) women suffered from vi degree of nerve palsy. the severity of palsy was higher in women (p<0.001). there were not significant correlations between the severities of palsy and age (p=0.08), recurrence rate (p=0.18), season (p=0.9), and comorbid disease including hypert ension (p=0.18), diabetes (p=0.29), and hyperlipidemia (p=0.94). the patients with any of following symptoms such as ear pain (p<0.001), taste disturbance (p<0.001), increased tearing (p=0.03), and hyperacusis (p<0.001) have more severe palsy (table 2). multivariate analysis showed that presence of ear pain (rr=1.31; 95%cl: 1.07-1.61; p=0.008), taste disturbance (rr=1.38; 95% cl: 1.13 1.69; p=0.002), increased tearing (rr=1.39; 95%cl: 1.07-1.80; p=0.01), and hyperacusis (rr=1.41; 95%cl: 1.14-1.76; p<0.001) were significantly associated with figure 1: percent of patient among age groups  figure 2: seasonal incidence of bell's palsy  figure 3: incidence of bell's palsy among severity of paralysis  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 66-70 68 increase in severity of palsy (table 3). discussion: the main finding of the present study revealed the equal gender and occupational distribution, higher incidence of disease in fourth decade of life, significant higher incidence in summer and autumn, significant higher grades of nerve damage (grade v and vi), and finally significant higher incidence of ear pain and taste disturbance in ifp patients. in addition, there were significant association between the severity of nerve damage and presence of any simultaneous symptoms including ear pain, taste disturbance, increased tearing, and hyperacusis. bell´s palsy is the most common cause of facial paralysis that occurs incidentally with idiopathic etiology. it has been reported that there is a greatest incidence of ifp in japanese and the mexican population compared to the smallest incidence in the swedish population (21). in a study carried out by monini et al in italy, it was reported that the age of peak incidence of ifp was 50 years and 53.7% of patients were male (22). in another study in korea, lee et al showed that the mean age of ifp was 47 years and 43.5% of patients with ifp were male (23). savadi oskouei et al showed the high incidence of ifp in 20-30 years patients and in cold seasons (18). the seasonal incidence of ifp has been discussed for many years. previous studies have found higher incidence of bell's palsy in autumn and winter, related to high prevalence of viral infection in the cold seasons (17, 24). movahedian et al stated that the high incidence of ifp occurs in autumn and winter (15). despite various studies on seasonal effects on ifp (16, 17, 25), the severity of seasonal effects of ifp in different areas and climate conditions are not well studied. in the present study, the most incidence of ifp has been observed in summer (37.2%) and autumn (33.1%) and fourth decade of life (30-44 years). previous studies demonstrated that activation of the latent herpes viruses by ultraviolet could cause ifp. people, who are more susceptible to ultraviolet, including farmers, are at the higher risk of ifp. this hypothesis is supported by a study performed by savadi oskooi et al showed that 90% of patients referred at midsummer were farmer (18). this study showed that the most patients were selfemployed (23.1%) and 18.2% farmers. recurrent ifp has been reported in different studies (26-30). soltanzadeh et al estimated that 9% of patients table 2: baseline characteristics of patients with bell’s palsy who had referred to the ed  variable n (%) p gender male 64 (52.9) ref female 57 (47.1) 0.525 occupational status self-employed 28 (23.1) ref housekeeper 26 (21.5) 0.79 employee 15(12.4) 0.05 farmer 22 (18.2) 0.40 construction worker 16 (13.2) 0.07 other 14(11.6) 0.06 comorbidity hypertension 27 (22.3) ref diabetes mellitus 23 (19.0) 0.57 hyperlipidemia 25 (20.7) 0.78 symptoms ear pain 53 (43.8) ref taste disturbance 47 (38.8) 0.55 increased tearing 14 (11.6) <0.001 hyperacusis 19 (15.7) <0.001 table 3: relationship between demographic and clinical factors with severity of palsy (univariate analysis)  variable severity of paresis p 1-4 4-6 age (years) 15-29 10 (34.5) 19 (56.5) 0.08 30-44 22 (66.7) 11 (33.3) 45-59 15 (53.6) 13 (46.4) 60-74 10 (58.8) 7 (41.2) >=70 10 (71.4) 4 (28.6) gender male 45 (70.3) 19 (29.7) <0.001 female 22 (38.6) 35 (61.4) times of refer first 49 (52.1) 45 (47.9) 0.18 second 18 (66.7) 9 (33.3) season spring 8 (50.0) 8 (50.0) 0.9 summer 26 (57.8) 19 (42.2) autumn 23 (57.5) 17 (42.5) winter 10 (50.0) 10 (50.0) comorbidity hypertension 18 (66.7) 9 (33.3) 0.18 diabetes mellitus 15 (65.2) 8 (34.78) 0.29 hyperlipidemia 14 (56.0) 11 (44.0) 0.94 symptoms ear pain 16 (30.2) 37 (69.8) <0.001 taste disturbance 13 (27.7) 34 (72.3) <0.001 increased tearing 4 (28.6) 10 (71.4) 0.03 hyperacusis 2 (10.5) 17 (89.5) <0.001 table 1: association between demographic and clinical factors with severity of palsy (multivariate analysis)  variable rra 95% cib p age 1.01 0.94-1.09 0.70 gender 1.16 0.96-1.38 0.12 ear pain 1.31 1.07-1.61 0.000 taste disturbance 1.38 1.13-1.69 <0.001 increased tearing 1.39 1.07-1.8 0.01 hyperacusis 1.41 1.14-1.76 <0.001 a: adjusted risk ratio b: confidence interval this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 69 zohrevand et al with ifp experienced the recurrence (31). in this study, recurrent ifp was observed in 22.3% of patients. in contrast to other studies, the higher recurrence rate observed in this study may be related to the lack of the patients’ follow-up after the first recovery. in a research performed by lee et al on ifp patients, it was shown that 63.3% of patients had a higher severity of nerve involvement (hb grade>iv) (23). according to the previous studies, it was found that 44.6% of ifp patients belonged to iv and v hb grades and only 21.5% of them had i and ii grades. the limitations of this investigation are that patients could not follow-up and the number of them was too small. this study recommends to design a greater prospective or casecontrol studies to recognize the related factors of ifp and confirm the data with a larger sample size. conclusion: there was equal gender and occupational distribution, higher incidence in fourth decade of life, higher incidence in summer and autumn, higher grades of nerve damage (grade v and vi), and higher incidence of ear pain and taste disturbance in patients suffered from ifp. in addition, there was significant association between the severity of nerve damage and the presence of any simultaneous symptom. acknowledgments: the authors appreciate the insightful cooperation of medical sciences and the staffs of the emergency department of poursina hospital in rasht. we thank the patients and their families participated in this study. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of 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5 (1): e69 or i g i n a l re s e a rc h blood lead levels in asymptomatic opium addict patients; a case control study kazem ghaemi1,2, atefeh ghoreishi3, navid rabiee3, samira alinejad3, esmaeil farzaneh4, alireza amirabadi zadeh3, mohammad abdollahi 5, omid mehrpour3∗ 1. atherosclerosis and coronary artery research center, birjand university of medical sciences, birjand, iran. 2. department of neurosurgery, birjand university of medical sciences, birjand, iran. 3. medical toxicology and drug abuse research center (mtdrc), birjand university of medical sciences, birjand, iran. 4. department of internal medicine, ardabil university of medical sciences, ardabil, iran. 5. toxicology and diseases group, pharmaceutical sciences research center, tehran university of medical sciences, tehran, iran. received: march 2017; accepted: june 2017; published online: 15 june 2017 abstract: introduction: one of the newest non-occupational sources of lead contamination is drug addiction, which has recently been addressed as a major source of lead poisoning in some countries. the present study aimed to investigate the blood lead level (bll) of asymptomatic opium addicts. methods: this case-control study was conducted during a one-year period to compare bll of three groups consisting of opium addicts, patients under methadone maintenance therapy (mmt), and healthy individuals. results: 99 participants with the mean age of 55.43±12.83 years were studied in three groups of 33 cases (53.5% male). the mean lead level in opium addicts, mmt and control groups were 80.30 ± 6.03 µg/l, 67.94 ± 4.42 µg/l, and 57.30±4.77 µg/l, respectively (p=0.008). there was no significant difference in bll between mmt and healthy individuals (p=0.433) and also between opium addicts and mmt individuals (p=0.271).oral opium abusers had significantly higher lead levels (p = 0.036). there was a significant correlation between bll and duration of drug abuse in opium addict cases (r=0.398, p=0.022). the odds ratio of having bll ≥ 100 in oral opium users was 2.1 (95% ci: 0.92 4.61; p = 0.43). conclusion: based on the result of present study, when compared to healthy individuals, opium addicts, especially those who took substance orally had significantly higher levels of blood lead, and their odds of having bll ≥ 100 was two times. therefore, screening for bll in opium addicts, particularly those with non-specific complaints, could be useful. keywords: lead; substance abuse treatment centers; methadone; opium; heroin; case-control studies © copyright (2017) shahid beheshti university of medical sciences cite this article as: ghaemi k, ghoreishi a, rabiee n, alinejad s, farzaneh e, amirabadi zadeh a, abdollahi m, mehrpour o. blood lead levels in asymptomatic opium addict patients; a case control study. 2017; 5(1): e69. 1. introduction l ead is a versatile metal, used in approximately 900 industries (1). due to its prevalence in various chemical derivatives (2), lead poisoning is a common problem particularly in developing countries. lead, is easily absorbed through skin, respiratory system, and gastrointestinal tract. it readily crosses the blood-brain barrier and pla∗corresponding author: omid mehrpour; medical toxicology and drug abuse research center (mtdrc), birjand university of medical sciences (bums), moallem avenue, birjand, iran, 9713643138. email: omid.mehrpour@yahoo.com.au mobile phone: +989155598571 centa after entering plasma and is spread in all soft and hard tissues. abdominal pain, anemia, fatigue, joint pain, headache, memory impairment, ataxia, peripheral neuropathy, deafness, kidney disease, weakened immunity, reduced birth weight, abortion, and premature birth are some of the most important signs of lead poisoning (2-4). although lead contamination usually occurs only when the individual has a history of contact with traditional sources of lead, new types of non-occupational poisoning have created some problems (5). one of the newest non-occupational sources of lead contamination is drug addiction, which has recently been addressed as a major source of lead poisoning in some countries, including iran (6). inorganic lead toxicity related to inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. ghaemi et al. 2 travenous injection or smoking of contaminated heroin has been reported since 1989 (7). other instances include processed cannabis, methamphetamine, and indian traditional herbal medicine (8-10). in asia, opium and cannabis have been reported as the drugs abused most frequently in recent decades (11). illicit opium may be adulterated with various materials like strychnine, paracetamol, and heavy metals such as lead and thallium (12). salesmen and smugglers may add heavy metals to opium to raise its weight for more benefit (13, 14). addition of lead into opium can cause an important health problem in iran and growing reports of lead poisoning due to drug abuse are alarming. based on above mentioned points, the present study was conducted to investigate blood lead level (bll) in opium addicts and compare it with healthy individuals and individuals under methadone maintenance therapy (mmt). 2. methods 2.1. study design and setting this case-control study was conducted during june to december 2014 to compare the bll of three groups, consisting of opium addicts (hospitalized in vali-e-asr hospital, birjand, iran), mmt cases (from the mmt clinic of imam reza hospital, mashhad, iran), and healthy companions of the patients as control group. the participants were enrolled only if they provided direct informed consent to participate in the study. the study protocol was reviewed and approved by ethics review committee of the birjand university of medical sciences under the code number 631. researchers adhered to confidentiality of patients’ information and declarations of helsinki. 2.2. participants opium addicts were selected randomly from asymptomatic patients hospitalized in ophthalmology ward with other common diagnoses like cataract, glaucoma, etc. and patients under mmt were selected randomly from patients of the mmt clinic. control group consisted of patients’ nonaddict family members in order to reduce the selection bias. case and control groups were matched based on age, sex and region. opium addicts were enrolled in this study only if they fulfilled dsm iv criteria for substance dependence. inclusion criterion for patients under mmt was its duration of more than six months. control group was selected from individuals who had no history of opioid exposure. suspected passive smoking (especially in control group), history of lead poisoning, known occupational contact with lead (e.g., plumbing, pottery, solder, battery making, and painting) and presence of an underlying systemic disease were considered as exclusion criteria. there was not any sex and age limitation. 2.3. data collection a checklist consisting of age, sex, type and duration of drug abuse, route of administration, duration of mmt, as well as bll was developed and filled for the participants. two ml of venous blood was collected from all participants in complete blood count (cbc) vials, stored at 4◦c and transferred to the toxicology laboratory of imam reza hospital, mashhad, iran, in ice-containing flasks for measurement of lead level. bll was measured by flame atomic absorption spectrophotometry (faas) method (perkin elmer 3030, usa). results were expressed in µg/l. 3 trained medical students were responsible for data gathering. laboratory technician was blind to the patients’ information. 2.4. statistical analysis sample size was determined based on study of khatibi. et al. (6) considering α=0.05, β=0.1 (power:0.9) and d= 1.72 (n=33 for each group). statistical analysis was performed using spss software 19. findings were reported as mean ± standard deviation or standard error and frequency (percentage). student t test for parametric and man whitney u-test for nonparametric variables were used for two group comparison. since bll had a normal distribution in each group, inter-group comparison was done by a parametric test (one way anova). the u.s. department of health and human services recommends that blls among all adults be reduced to <100 (15). therefor 100 µg/l was considered as a cut point for determining at risk individuals. p-value less than 0.05 was considered statistically significant. 3. results 3.1. baseline characteristics 99 participants with the mean age of 55.43±12.83 years (2586) were studied in three groups of 33 cases (53.5% male). there was no significant age (p = 0.13) and sex (p = 0.07) difference between the groups. the route of opium administration in addict patients was ingestion in 16 (48.4%) cases, inhalation in 8 (24.2%), and mixed in 9 (27.3%). 15 (45.5%) cases used opium, 14 (42.4%) cases opium residue (shireh), 2 (6.0%) cases heroin, and 2 (6.0%) iranian crystal (heroin base). duration of drug abuse was 18.21 ± 2.47 (1 50) years among the opium addicted. duration of mmt was 21.39 ± 3.13 (0.560) months in mmt group and they had previous drug abuse duration of 10.88 ± 1.76 years. 3.2. lead levels the mean lead level in opium addicts, mmt and control groups were 80.30 ± 6.03 µg/l, 67.94 ± 4.42 µg/l, and 57.30±4.77 µg/l, respectively (p=0.008). there was no significant difference in bll between mmt and healthy indithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e69 viduals (p=0.433) and also between opium addicts and mmt individuals (p=0.271). table 1 compares the blood lead levels of opium addicts based on sex, age, route of administration and type of drug. oral opium abusers had significantly higher lead levels (p = 0.036). there was a significant correlation between bll and duration of drug abuse in opium addict cases (r=0.398, p=0.022). table 2 shows the distribution of bll below and over 100 µg/l in the studied groups. the odds ratio of having bll ≥ 100 in oral opium users was 2.1 (95% ci: 0.92 4.61; p = 0.43). 4. discussion based on the result of present study, when compared to healthy individuals, opium addicts, especially those who took substance orally had significantly higher levels of blood lead, and their odds of having bll ≥ 100 was two times. mmt group also had a higher bll in comparison with healthy individuals but the difference was not significant. iran’s shared border with afghanistan (the world’s largest drug manufacturer) has turned it into one of the main routes of trafficking drugs into europe. therefore, iran could potentially be influenced by complications caused by drug abuse (16). traditional opioids (opium and its extract) were the most frequently used drugs by the opium addicts in our study, which is consistent with other studies (17-19). 9.1% of healthy individuals had bll over 100 µg/l, which is considered acceptable for birjand city region in comparison with the result of a study conducted on healthy individual in arak, iran. they reported 40.5% of participants, had bll more than 10 µg /dl (20). u.s. department of health and human services has designated 100 âţg/l of whole blood as the reference bll for adults (15). thus, the most recent guidelines for the management of lead-exposed adults carried out by the medical community at the current center of disease control (cdc/niosh) reference bll of 100 µg/l (3). salehi et al. demonstrated that 40% of the studied opium addicts had a bll over 250 µg/l (21). in addition, in a study by shiri et al. three inpatients with lead poisoning symptoms had a mean bll of 820 µg/l (22). the disagreement of the findings between other studies and the present study could be due to the particular method used for bll measurement. in the cited studies, bll was measured in symptomatic patients with confirmed diagnosis of lead poisoning, while only five of 33 (less than 5%) hospitalized patients in the present study had some degree of abdominal pain, and none of them were diagnosed as poisoned with lead. in this study, mean bll in opium addicts was significantly higher than in controls, which is consistent with results described by salehi et al., farzin et al., abbasi et al. and khatibi-moghadam et al. (6,21,23-24). increased bll in the opium addicts could be attributed to lead contamination due to opiate abuse. the mean bll measured in opium addicts ingesting the drug was significantly higher than other route of administration. these findings are in line with the results of hashemi domeneh et al. who found a significantly higher level of lead in drug abusers who prefer the oral route of ingestion (25). previous studies demonstrated that the heat associated with smoking opium may affect the amount of lead absorbed into the blood. on the contrary, the lead is not affected in oral routes of ingestion, leading to higher levels of absorption into the blood, leading to higher blls (25). bll was higher in mmt group in comparison to healthy controls which was predictable because patients under mmt were used to opium abuse and therefore, had lead exposure, which has a long half-life in the body reported to be up to 20 years. besides, our findings demonstrated a lower bll in patients under mmt than opium addicts, which could represent a decreased risk of lead poisoning after withdrawal, however, the difference in bll between the patients under methadone therapy and the opium addicts was not significant. currently, opium addiction has become a major problem in some countries and has increased the rate of lead poisoning that is almost hidden for the physicians and they do not have enough training on how to treat those cases. warning the health professionals about toxicological aspects of this issue is very important. therefore, screening for bll in opium addicts, particularly those with non-specific complaints, could be useful. this is the first study in this regard, describing this phenomenon in the south khorasan province. the results presented here are initial findings and can be expanded in future studies employing larger sample sizes, which are more likely to be representative of the whole population. 5. limitation one of the limitations of our study was the use of matched controls. matching was done just based on age, sex and region. in this regard, duration of drug abuse in the groups was not completely matched so conclusion regarding influence of mmt on bll should be considered with caution. there was no evidence regarding the use (current or past) of opium, or other exposures that might contribute to elevated blood lead measurements in our control individuals. therefore, we had to rely on their self-stated history. moreover, due to lower socio-cultural status of opium addicts, explanation of the simplest objectives of the study was quite difficult. besides, we have just evaluated bll in opium addicts while other contaminations could be present in opium that need further study. another limitation of our study was lack of confirmation of absence of lead contamination of blood by other sources. however, a history of lead poisoning and known occupational contact with lead (e.g., plumbing, pottery, solder, battery making, and painting) were considered this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. ghaemi et al. 4 table 1: blood lead levels of opium addicts based on sex, age, route of administration and type of drug variable n (%) lead level (µg/l) p value sex male 36 83.75±5.43 0.01 female 27 64.00±4.80 age (year) 25-40 15 61.73±7.67 40-65 54 69.20±4.21 0.63 >65 30 70.67±5.62 route of administration ingestion 16 (48.48) 96.94 ± 8.56 inhalation 8 (24.24) 65.63 ± 12.36 0.036 mix 9 (24.27) 66.56 ± 8.58 type of drug heroin 2 (6.06) 49.50 ± 1.49 opium 15 (45.45) 79.67± 8.60 0.607 opium residue (shireh) 14 (42.42) 85.57± 10.08 iranian crystal (heroin based) 2 (6.06) 108.00 ± 9.37 data were presented as mean ± standard error. table 2: distribution of bll ≥ 100 îijg/l between the studied groups groups n (%) bll < 100 n (%) bll ≥ 100 p value opium addicts 23 (9.7) 62.61 ± 4.63 10 (30.3) 121.00 ± 6.16 methadone users 29 (87.9) 60.76 ± 3.09 4 (12.1) 120.00 ± 6.33 0.047 methadone users 29 (87.9) 60.76 ± 3.09 4 (12.1) 120.00 ± 6.33 healthy controls 30 (90.9) 51.40 ± 3.70 3 (9.1) 116.33 ± 9.86 data were presented as mean ± standard error. as the exclusion criteria. moreover, it is possible that the elevated blls reported in this study were the result of patient exposure to a wide range of potential lead sources that were impossible to control for such as food, air pollution to lead, etc. unfortunately, opium used by addicts was not accessible and we couldn’t analyze them for lead to ascertain the conclusion. 6. conclusion based on the result of present study, when compared to healthy individuals, opium addicts, especially those who took substance orally had significantly higher levels of blood lead, and their odds of having bll ≥ 100 was two times. therefore, screening for bll in opium addicts, particularly those with non-specific complaints, could be useful. 7. appendix 7.1. acknowledgements the authors would like to acknowledge the support of medical toxicology and drug abuse research center (mtdrc) in birjand university of medical sciences. 7.2. author contribution kazem ghaemi, omid mehrpour and mohammad abdollahi were responsible for study conception and design; atefeh ghoreishi, navid rabiee and samira alinejad performed sampling and data collection. alireza amirabadizadeh and esmaeil farzaneh performed data analysis. atefeh ghoreishi, navid rabiee and samira alinejad prepared the draft of the manuscript. kazem ghaemi and mohammad abdollahi assisted in english editing. omid mehrpour completed and revised the manuscript. 7.3. funding/support this work was supported by birjand university of medical sciences under the grant number 631. 7.4. conflict of interest the authors do not have any conflict of interest to disclose. references 1. mohammadi s, mehrparvar a, aghilinejad m. appendectomy due to lead poisoning: a case-report. j occup med toxicol. 2008;17(3):23. this 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afshari r, mehrpour o. thallium exists in opioid poisoned patients. daru journal of pharmaceutical sciences. 2015;23(1):1. 13. karrari p, mehrpour o, abdollahi m. a systematic review on status of lead pollution and toxicity in iran; guidance for preventive measures. daru journal of pharmaceutical sciences. 2012;20(1):1. 14. mehrpour o, karrari p, abdollahi m. chronic lead poisoning in iran; a silent disease. daru journal of pharmaceutical sciences. 2012;20(1):1. 15. cdc. adult blood lead epidemiology and surveillance (ables). cincinnati, oh: us department of health and human services, cdc, national institute for occupational safety and health; 2013. available at http://www.cdc.gov/niosh/topics/ables/description.html 16. mehrpour o, sheikhazadi a, barzegar a, husein a, malic c, sheikhazadi e, saberi-anary sh. comparison of quantitative and qualitative dermatoglyphic characteristics of opium addicts with healthy individuals. addiction & health. 2016 apr; 8(2):76.. 17. abbasi a, taziki sa, av m. the proto type of drug misabused of opioids in the self-introduced addicts in gorgan. journal of gorgan university of medical science. 2006;8(17):22-7. 18. afghah s, khalilian a. survey of factors related to opioid dependency in mazandaran province. journal of mazandaran university of medical sciences. 1996;6(12):29-35. 19. malekinejad m, vazirian m. transition to injection amongst opioid users in iran: implications for harm reduction. international journal of drug policy. 2012;23(4):333-7. 20. moayedi s fa, mohajerani h, seyed am. the relationship between blood lead levels and clinical syndromes in residents of arak, iran. research in medicine. 2008;32(1):5. 21. salehi h, sayadi ar, tashakori m, yazdandoost r, soltanpoor n, sadeghi h, et al. comparison of serum lead level in oral opium addicts with healthy control group. archives of iranian medicine. 2009;12(6):555-8. 22. shiri r, ansari m, ranta m, falah-hassani k. lead poisoning and recurrent abdominal pain. industrial health. 2007;45(3):494-6. 23. farzin l, amiri m, shams h, faghih maa, moassesi me. blood levels of lead, cadmium, and mercury in residents of tehran. biological trace element research. 2008;123(13):14-26. 24. abbasi mmh, ansari m, shahesmaeili a, qaraie a. lead serum levels in opium-dependent individuals. addiction & health. 2009;1(2):106. 25. hashemi domeneh b, tavakoli n, jafari n. blood lead level in opium dependents and its association with anemia: a cross-sectional study from the capital of iran. 2014. 2014;19(10). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2017; 5 (1): e77 doi:10.22037/emergency.v5i1.18276 or i g i n a l re s e a rc h demographics of scorpion sting in iran; a cross sectional study babak mahshidfar1, hamed basir ghafouri2, mohammad reza yasinzadeh1, mani mofidi1, mahdi rezai1, davood farsi1, saeed abbasi1, peyman hafezimoghadam1∗ 1. emergency medicine management research center, rasoul-e-akram hospital, iran university of medical sciences, tehran, iran. 2. trauma and injury research center, iran university of medical sciences, tehran, iran. received: june 2017; accepted: august 2017; published online: 21 august 2017 abstract: introduction: scorpion sting is an important public health problem in some countries, including iran. this study aimed to describe the demographics of a large number of these victims in some endemic areas of iran. methods: this cross-sectional study evaluated baseline characteristics, clinical findings, management, and disposition of scorpion stung cases in 26 cities of 4 provinces in the southwest quarter of iran, during one year. results: 3008 cases of scorpion sting with mean age of 27.07 ± 16.58 years were studied (51.3% female). the mean time from sting to hospital was 1.89 ± 1.04 hours. no first aid measures had been taken in 96.6% of cases. lower (39.5%) and upper (35.7%) extremities were stung most frequently. midnight to 6:00 am was the period of time most of stings occurred (34.2%). local pain (77.2%) and erythema (63.5) were among the most common signs and symptoms. 2026 (67.3%) victims had been discharged; 326 (10.8%) were admitted or referred to other hospitals and 5 (0.2%) cases died. conclusion: it seems that demographic characteristics of scorpion sting in iran are not so different from those reported from other sites of the world, as signs and symptoms of local and systemic envenomations. victims, companions, and healthcare providers perform many futile and maybe harmful measures and there is a need to educate all about all of these details. keywords: iran; scorpion stings; epidemiologic studies; emergency service, hospital © copyright (2017) shahid beheshti university of medical sciences cite this article as: mahshidfar b, basir ghafouri h, yasinzadeh m, mofidi m, rezai m, farsi d, abbasi s, hafezimoghadam p. demographics of scorpion sting in iran; a cross sectional study. emergency. 2017; 5(1): e77. 1. introduction s corpion sting is an important public health problem in some countries, including iran. the scorpion envenomation mortality rate is estimated to be about 0.27% and some of the species could kill their victims in about 7 hours (1). at least 1 million scorpion stings are estimated to occur annually around the world, leading to more than 3250 deaths (2, 3). in iran, scorpions have been classified in 23 families, 8-10 genera, 18-32 species, and 7-17 subspecies; and they have threatened a relatively large population in significant regions (4-7). approximately 40000-50000 cases of scorpion sting have been recorded, annually in iran, with about 19 deaths each year (8, 9). in iran, there were 42,850 ∗corresponding author: peyman hafezimoghadam; emergency medicine management research center, rasoul-e-akram hospital, niayesh street, sattarkhan street., tehran, iran. tel: +989123478773 email: hafezimoghadam@yahoo.com scorpion sting events reported with 14 deaths in 2005 compared to 45950 cases with 18 deaths in 2006. khuzestan and hormozgan are two iranian provinces having lots of scorpion sting cases reported, annually (4, 10). the true incidence of scorpion sting events is unclear, because some cases do not request medical attention. epidemiologic studies may improve the determinants of scorpion sting in order to plan and implement effective public health interventions. recognition of clinical presentations and complications of scorpion sting is invaluable as it could light the way to therapeutic strategies. the other important aspect of encountering scorpions is that we should train skilled physicians who can accurately determine the type of scorpions and know the characteristics of scorpions endemic to an area. this strategy can lead to a rapid and correct selection of therapeutic modalities (11, 12). in this study we tried to describe demographics of a large population of these victims presenting to emergency departments (ed) of endemic areas in iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. mahshidfar et al. 2 table 1: baseline characteristics of studied patients variables number (%) sex female 1523 (51.3) male 1443 (48.6) age (year) <20 994 (34.0) 20-39 1315 (45.0) 40-59 463 (15.8) 60-79 132 (4.5) >80 19 (0.7) pervious bite yes 1116 (49.7) no 1129 (50.3) time to hospital (hour) <1.5 1328 (51.0) 1.5-3 457 (17.6) 3-6 584 (22.4) >6 231 (8.9) province khuzestan 1709 (71.6) kohkiluye boyerahmad 488 (20.4) hormozgan 146 (6.1) kerman 45 (1.8) season spring 29 (1.0) summer 1164 (40.6) autumn 1563 (54.5) winter 114 (4.0) pre-hospital management none 1339 (92.9) tourniquet 38 (2.6) analgesic 25 (1.7) wound sucking 24 (1.7) disinfection 9 (0.6) onion application 6 (0.4) 2. methods 2.1. study design and setting in this cross-sectional study, we evaluated the baseline characteristics, clinical findings, management, and disposition of scorpion stung cases in 26 cities of 4 provinces in the southwest quarter of iran (khuzestan, kohkiluye boyerahmad, hormozgan, and kerman), during april to december 2009. our study protocol was approved by the ethics committee of iran university of medical sciences (iums). all authors adhered to world medical association declaration of helsinki, ethical principles for medical research involving human subjects. 2.2. participants all scorpion stung patients referring to the governmental clinics (both outpatients and those admitted) in the defined cities with available data on hospital information system (his), were included. there was not any sex or age limitatable 2: characteristics of stings variables number (%) location upper extremities 1073 (38.4) lower extremities 1187 (42.5) head and neck 124 (4.4) trunk 411 (14.7) time 0-6 1030 (44.9) 6-12 450 (19.6) 12-18 302 (13.2) 18-24 506 (22.1) scorpion color yellow 1534 (59.9) black 629 (24.5) unknown 399 (15.6) tion. patients with missing data were excluded. 2.3. data collecting a comprehensive database including demographic information (sex, age, etc.), scorpion characteristics, time of sting, history of previous sting, site of body stung, clinical signs and symptoms, as well as prehospital and ed management (antivenom, antibiotic, corticosteroid, etc.) and disposition of patients were filled by the physician in charge. 2.4. statistical analysis statistical analyses were performed with spss_ 21 and descriptive findings were presented as frequency and percentage or mean ± standard deviation. 3. results 3.1. baseline characteristics data of 3008 cases of scorpion sting with mean age of 27.07 ± 16.58 (5 month99) years were collected (51.3% female). 1315 (45%) cases were in the age range of 20 -39 years. tables 1 and 2 show the baseline characteristics of the studied patients. most cases (71.6%) were recorded in khuzestan province. the mean time from sting to hospital referral was 1.89 ± 1.04 hours and most victims had been referred to medical facilities within 1.5 hours following stings (44.1%). only 7.7% of patients were visited after 6 hours following stings. no first aid measure had been taken in 96.6% of cases; among first aid measures taken, tight bandage of stung site had most frequently been done, followed by incision and suction of the site and analgesic use. lower extremities were stung most frequently (39.5%), followed by upper extremities (35.7%). midnight to 6:00 am was the period of time most of stings occurred (34.2%). in 51% of cases, the scorpion had been dethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e77 scribed as yellow and in 20.9% as black; in the rest of forms, color of scorpion had not been defined. 3.2. clinical findings clinical findings of patients are summarized in table 3. pain (77.2%) and erythema (63.5%), tachycardia (3.6%), agitation (1.0%), mouth xerosis (5.6%), hematuria (1.6%) and rash (2.4%) were among the most common local, cardiopulmonary, neurologic, gastrointestinal, urologic, and skin problems, respectively. urinalysis (u/a) was performed for 1688 (56.1%) cases; 21% of which had hematuria. 3.3. management polyvalent scorpion anti-venom had been prescribed for 2489 (82.7%) victims (87.3% intramuscular and 12.7% intravenous). 132 (5.3%) victims were given more than one vial of anti-venom, 35 (1.4%) of which experienced an acute hypersensitivity reaction; 17 cases were limited to skin. skin test for anti-venom had been accomplished in 2383 (79.2%) of victims. the other medications prescribed included antihistamines (46.9%), systemic corticosteroids (36.2%), analgesics (24.9%), anti-microbial (10.4%), atropine (0.4%), and anti-hypertensive (0.2%). 3.4. disposition 2026 (67.3%) victims had been recovered in eds and were discharged; 326 (10.8%) had been admitted or referred to other hospitals. 5 (0.2%) cases died; all of them had been given anti-venom. 4. discussion the majority of studies from iran and other countries have reported that scorpion stings are more prevalent in summer, especially july (13-18). our data showed that most of the stings recorded occurred during october, september, and november. the envenomation episodes had occurred almost equally in males and females confirming the results of most studies done before; although, certain studies showed a male preference and in one study from brazil, victims were predominantly female (2, 6, 11, 13, 19-23). the 20-30 years age group was the most affected one, similar to the results reported by the other studies from iran and other countries (2, 3, 6, 13, 23, 24). the time between sting and ed arrival was acceptable and similar to most previous studies (20, 23). in the current study, lower extremities followed by upper extremities were shown to be more commonly stung, compared with other parts of the body, in line with the results reported by dehghani, nejati, and barros (6, 11, 23). it can be due to the fact that people of the studied regions wear table 3: clinical findings of studied patients variables number (%) local pain 2157 (77.2) erythema 1774 (63.5) muscular pain 165 (5.9) numbness 160 (5.7) cardiopulmonary tachycardia 101 (3.6) bradycardia 23 (0.8) hypertension 29 (1.0) hypotension 10 (0.4) dysrhythmia 7 (0.3) respiratory distress 17 (0.6) wheezing 3 (0.1) pulmonary edema 1 (0.03) neurologic agitation 28 (1.0) irritability 25 (0.9) paresthesia 24 (0.9) confusion 5 (0.2) seizure 5 (0.2) fasciculation 2 (0.1) gastrointestinal mouth xerosis 156 (5.6) nausea and vomiting 119 (4.3) hyper salivation 34 (1.2) abdominal pain 19 (0.7) diarrhea 7 (0.3) urologic hematuria 45 (1.6) urinary retention 9 (0.3) frequency 7 (0.3) priapism 2 (0.1) skin rash 67 (2.4) anaphylaxis 6 (0.2) angioedema 4 (0.1) unsecured shoes due to their low socio-economic status and children walk around with bare feet and play with stones. yellow scorpions were responsible for half of the stings; however, the color of the scorpions remained unknown in 20% of the cases. other studies from iran have reported similar result (11, 20). two investigations in turkey found that black scorpion sting events were more prevalent than others (25, 26). on-scene managements were done for only 7% of the victims in our study. this finding was in contrast to a study that first aids were done in 95% of sting episodes (25). ligation, immobilization, cutting, sucking, and cleaning of the site of sting were done mostly (13). studies have revealed that venom of scorpion stimulates the sympathetic system and increases blood pressure (hypertension) and heart rate (tachycardia) and induces cardiac dysrhythmias (18). it stimulates catecholamine release in body that leads to anxiety, agitation, tachycardia, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. mahshidfar et al. 4 hypertension, fever, and sweating. it also stimulates the parasympathetic system transiently causing urinary retention, sweating, and sialorrhea (27). in the current study, local signs and symptoms including pain and erythema were more common. other frequent symptoms or signs were restlessness, tachycardia, dry mouth, hematuria, flank pain, and urticarial rash. these findings have been frequently mentioned in previous studies (13, 18). in 2002, a study reported 261 sting events in birjand with clinical presentations including pain, paresthesia, erythema, and itching in 100% of cases. agitation, sweating, and nausea were seen in 20% of them. no seizure, dysrhythmia, or hemodynamic instability were seen (18). in a study conducted in 2001-2011, 790 envenomation episodes were assessed in qom province of iran. the clinical presentations included pain at the site of envenomation (82%), local redness (9%), hypoesthesia and numbness (12.5%), and severe muscle pain (0.7%). in that study, 97% of victims did not show neurologic symptoms; positive neurologic symptoms had involved sympathetic (2%), parasympathetic (0.5%), and central nervous system (0.2%) (20). barros studied 2283 scorpion sting victims in the years 2007-2012 in brazil. the most frequent local manifestations were pain (96.14%), edema (30.35%), and paresthesia (19.92%). while generalized pains (1.66%), vagal manifestations (1.05%), and arterial hypotension (0.26%) were among the most frequent systemic clinical manifestations. local pain was notified in almost 100% of the cases (23). in saudi arabia, 251 scorpion envenomed cases were reported in the years 1986-2000. 95% of victims had local pain and 78.3% had systemic presentations such as hypertension, hypersalivation, and sweating (14). management of scorpion sting includes fluid and electrolyte replacement, antibiotics in some cases, tetanus immunization, anti-venom, and analgesics (25). the use of anti-venom has been further challenged, because it could result in allergic complications. however, it is commonly believed that anti-venom therapy is the most effective treatment (28). in the current study, about 82% of patients received anti-venom. with regard to other studies done in iran, anti-venom is used in the majority of scorpion sting episodes (2, 6, 20). the mortality of scorpion sting was 0.2%, which is higher than those reported in previous studies. studies from turkey, saudi arabia, and iran (qom) reported no lethality (6, 13, 14, 20, 25). dehghani et al. evaluated 418 scorpion sting cases in khuzestan province in 2003 and the mortality rate was 0.05% (11). bouaziz et al. found that the following factors correlated with a poor outcome in scorpion stings: age less than 5 years, fever more than 38.5◦c, glasgow coma score (gcs) equal to 8/15 or less, pulmonary edema, leukocytosis more than 25,000 cells/mm3, and blood urea level above 8 mmol/l (29). others stated that factors such as victim’s age, weight, and health status, site of body stung, time of sting, and type of scorpion have important roles in severity of envenomation. envenomation is more dangerous in both extremes of age and victims with lower weight (25, 30). scorpion envenomation is still a health problem in iran and planning educational strategies for its prevention and management is necessary; we cannot overcome this hazard without optimal identification of the epidemiology of scorpions and the clinical manifestations of envenomation. although the majority of sting events occurred in the south of the country, but this problem has extended to the capital, tehran; 2.7% of mortalities in loghman hakim poison center is related to scorpion sting (31). obviously, the results can provide the health care providers with valuable information about the similarities and differences of such complications compared with other places in the world. it would guide us in designing protocols and guidelines to evaluate and manage the victims. 5. limitation old data is an important limitation of the present study but considering the large sample size, the finding could be representative of the demographic features of scorpion bite during that time period. 6. conclusion it seems that demographic characteristics of scorpion sting in iran are not so different from those reported from other sites of the world, as signs and symptoms of local and systemic envenomations. victims, companions, and healthcare providers perform many futile and maybe harmful measures and there is a need to educate all about all of these details. 7. appendix 7.1. acknowledgements the efforts of all emergency departments’ staff in data gathering and participating in other parts of the study are appreciated. 7.2. author contribution all authors pass the four criteria for authorship contribution based on the international committee of medical journal editors (icmje) recommendations. 7.3. funding/support none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e77 7.4. conflict of interest none. references 1. chippaux j-p, goyffon m. epidemiology of scorpionism: a global appraisal. acta tropica. 2008;107(2):71-9. 2. rafizadeh s, rafinejad j, rassi y. epidemiology of scorpionism in iran during 2009. journal of arthropod-borne diseases. 2013;7(1):66. 3. sedaghat m, salehi ma, dehghani r. mapping the distribution of some important scorpions collected in the past five decades in iran. annals of military and health sciences research 2012;9(4):285-96. 4. jalali a, rahim f. epidemiological review of scorpion envenomation in iran. iran j pharm res. 2014;13(3):743-56. 5. kovarik f. results of the czech biological expedition to 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limitation conclusion appendix references archives of academic emergency medicine. 2023; 11(1): e43 or i g i n a l re s e a rc h the effects of 3-month rosuvastatin adjuvant therapy on post thrombotic syndrome following deep vein thrombosis; a randomized clinical trial mehdi pishgahi1, shirin ghane fard2, rahil lak tabriz1, kimia karimi toudeshki1∗, zahra talebi3 1. department of cardiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. pediatric endocrinologist, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. received: april 2023; accepted: may 2023; published online: 10 june 2023 abstract: introduction: statins are known to have anticoagulation and anti-inflammatory effects. this study aimed to investigate the effect of rosuvastatin in reduction of post thrombotic syndrome (pts) following deep vein thrombosis (dvt). methods: in this randomized clinical trial, patients who were diagnosed with dvt of lower extremity were randomly assigned to 4 treatment groups: group 1: warfarin, group 2: warfarin + rosuvastatin, group 3: rivaroxaban, and group 4: rivaroxaban + rosuvastatin. the treatments were followed for 3 months and prevalence of pts (as primary outcome), as well as the changes in serum levels of d-dimer and c reactive protein (crp), and the extent of thrombosis before and after the intervention (as secondary outcomes) were compared between groups. results: 182 patients with the mean age of 55.22 ± 4.1 years finished the trial period (51.64% male). there was no significant difference between the groups regarding the baseline characteristics. based on the brandjes score, 31 (17.03%) patients had pts at the end of the study. the occurrence of pts was significantly lower in the groups taking statins (p<0.0001). although the change in the mean difference of legs circumference before and after intervention, were significant in all groups (p < 0.05), the differences was more prominent in groups 2 and 4 (p < 0.0001). after 3 months of taking medication, decrease of crp was more prominent in the statin groups (p = 0.001), and most cases with normal crp were in statin groups. among the patients with the serum d-dimer level above 10000 ng/ml, patients in the statin groups experienced significantly more reduction in d-dimer levels than the other groups (p<0.001). conclusion: rosuvastatin administration in combination with rivaroxaban or warfarin significantly reduces the level of inflammatory factors including crp and d-dimer, compared to patients receiving anticoagulants alone. rosuvastatin administration can significantly reduce the incidence of pts and cause a difference in the size of the lower limbs within 3 months. keywords: venous thrombosis; postthrombotic syndrome; rosuvastatin calcium; rivaroxaban; warfarin; anticoagulants cite this article as: pishgahi m, ghane fard s, lak tabriz r, karimi toudeshki k, talebi z. the effects of 3-month rosuvastatin adjuvant therapy on post thrombotic syndrome following deep vein thrombosis; a randomized clinical trial. arch acad emerg med. 2023; 11(1): e43. https://doi.org/10.22037/aaem.v11i1.1972. 1. introduction deep vein thrombosis (dvt) and acute pulmonary embolism (pe) are two presentations of venous thromboembolism (vte). dvt can impose a significant burden on the patient’s life; especially when it leads to pulmonary embolism (1). it has been reported that dvts of the proximal veins of the lower extremities may be more likely to create ∗corresponding author: kimia karimi toudeshki; cardiology department, shohada-e-tajrish hospital, qods sq., tajrish, tehran, iran. tel: (+98)2122718000, email: kymya77@yahoo.com, orcid: https://orcid.org/0000-0001-7560-7091. edema compared to others; resulting in different circumferences of the lower limbs in unilateral cases (2). dvt treatment mainly involves anticoagulation when there is no contraindication. afterwards, measures are taken to prevent future recurrences, embolism, and thrombosis-related complications (1). it has been shown that treatment with novel oral anticoagulants (noacs) reduces the duration of hospitalization of patients in comparison to low molecular weight heparin (lmwh), warfarin or unfractionated heparin (ufh) (3). post thrombosis syndrome (pts) is the most common longterm complication of deep venous thrombosis (dvt) (4). pts is the result of chronic venous insufficiency, which develops following deep vein thrombosis (dvt). this chronic venous this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. pishgahi et al. 2 insufficiency is due to valvular incompetence and venous hypertension that follows the thrombotic obstruction. elevated d-dimer level is commonly used as a predictor of postthrombotic syndrome, since it is the consequence of persistent activation of clotting or inflammatory pathways (5). pts significantly reduces the quality of life with a wide range of adverse effects from minor inflammation, edema, and pain to severe complications such as venous stasis ulcers (6). patients with extensive dvt, recurrence of thrombosis on the same side of the body, a history of varicose veins, obesity, or residual thrombosis are at increased risk of developing pts (6). the best treatment strategy for prevention of pts is still unclear (7). maintaining an appropriate international normalized ratio (inr) for warfarin, use of the catheter lysis method, and long-term treatment with low molecular weight heparin (lmwh) are suggested to reduce the risk of developing pts (8, 9). on the other hand, the jupiter trial (2009) demonstrated a significant improvement in non-hyperlipidemic dvt patients, with elevated c-reactive protein (crp) levels, when treated with rosuvastatin. in addition to decreasing cholesterol levels and crp, treatment with statin seems to influence the process of coagulation by inhibiting tissue factor activity and activating platelets by reducing the expression of cd40l or p-selectin (10). but the ability of statins to reduce the incidence of pts is still unclear for physicians and researchers. san norberto et al. evaluated the use of statin therapy (rosuvastatin 10 mg or 5 mg) in prevention of pts in dvt patients over 70 years old (11). in this study, although a statistically significant difference in the primary outcome (ddimer) was not observed, a significant reduction in serum crp levels and the incidence of pts was seen in participants treated with rosuvastatin (villalta score higher than 5, 38.3% vs. 48.5%, p =0.019) (11). it has been hypothesized that inflammatory mediators released due to thrombus formation may induce valvular damage, leading to pts (12-14). also, a positive association between level of inflammatory markers (such as crp, and intercellular adhesion molecule 1 (icam1)) with pts development have been reported. considering the effect of rosuvastatin for inhibition of icam-1 expression (15), the idea of investigating its effect on prevention of pts may be considered. statins are easy to use, cheap and very safe and do not increase the risk of bleeding; and according to available data, they can be valuable in the treatment and prevention of recurrence of vte. this study aimed to evaluate the effect of rosuvastatin adjuvant therapy along with common anticoagulants on the improvement of treatment outcome and reduction of pts incidence in patients with acute dvt. 2. methods 2.1. study design and setting this randomized controlled trial was conducted on patients with established acute dvt, admitted to shohadaye tajrish, modarres, and labbafi nejad hospitals (affiliated to shahid beheshti university of medical sciences), tehran, iran, from september 25, 2017 to september 20, 2018 to evaluate the effects of rosuvastatin on 3-mounth outcomes. the study protocol was approved by research ethics committee of shahid beheshti university of medical sciences, tehran, iran (ir.sbmu.rec.1396.651), registered in iranian registry of clinical trials (irct20150621022852n4), and conducted adhering to principles of helsinki declaration. patients were assured that all information will remain confidential and anonymous. all patients provided written informed consent for participation. 2.2. participants inclusion criteria consisted of age over 18 and established acute dvt diagnosed via doppler ultrasonography by an expert attending radiologist. patients with endstage renal disease (esrd) who underwent routine dialysis and/or patients with glomerular filtration rate (gfr) below 30ml/min/1.73 m2, patients diagnosed with cancer before or during the trial, conditions such as infections and/or sepsis, which could affect serum inflammation factors and d-dimer levels, those with prior statin use, a contraindication for statin therapy (such as liver disease, severe myopathy during the treatment, etc.), bilateral dvt, loss to followup during the 3 months of trial for any reason including unwillingness of participants, and death during the trial period, were excluded. in addition, patients with chronic or acute on chronic dvt (based on the ultrasonography results) were also excluded. 2.3. data gathering and intervention demographic data and patient history were obtained through patient interviews and extent and area of thrombosis were determined via physical exam and doppler ultrasonography. diagnostic tests such as serum crp level, serum d-dimer, assessment of thrombosis area with doppler ultrasonography (by an attending radiologist unaware of patient allocations) were performed. computer software was used for permuted block randomization of patients into 4 groups (with 52 patients in each group) for treatment regimen allocation: group 1: warfarin; group 2: warfarin + rosuvastatin; group 3: rivaroxaban; group 4: rivaroxaban + rosuvastatin. the first arm received warfarin following initial heparin infusion, the standard therapy, with the aim of reaching the target inr of 2-3. in the second arm, in addition to warfarin, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e43 rosuvastatin 20mg (rosurexin® tablet 20mg, manufactured by actoverco pharmaceutical factory, karaj, iran) was administered once daily. the third arm received rivaroxaban 15mg twice a day in the first 3 weeks and then 20mg once daily. in the fourth arm, rosuvastatin was added to rivaroxaban regimen for treatment with the dosage mentioned previously. dose was adjusted for patients with renal impairment. use of compression stockings was advised for all patients according to treatment protocols in time with the initiation of medications. all patients were followed up every 2 weeks by phone for adherence to treatment regimen. after 3 months, crp and d-dimer levels, difference in swelling between two calves-diameter of circumference of calf 4 cm below the tuberosity of tibia bone, and occurrence of pts were assessed again for all patients and the results were compared to previous data of the patient and the data from other groups. if the patients had infections in their second visit for crp assessment, the assessment was postponed for another 2 weeks. in this study, the occurrence of pts was confirmed based on brandjes criteria, which consists of two sets of subjective and objective items. subjective items (symptoms) include spontaneous pain in calf, spontaneous pain in thigh, pain on standing/walking, pain in thigh on standing/walking, edema of foot/calf, heaviness of leg, spontaneous pain and pain on walking/standing, and impairment of daily activities; each one having one point. objective items (signs) include calf circumference increase by 1 cm, ankle circumference increase by 1 cm, pigmentation, venectasia, newly formed varicosis, phlebitis, and venous ulcer; each one having one point except the venous ulcer, which has 4 points. patients with a score of 3 are considered mild, while 4 is considered moderate, and scores 5 or more or any score along with ulceration of the limb are considered severe pts. 2.4. outcomes the treatments were followed for 3 months and prevalence of pts (as primary outcome), as well as the changes in serum levels of d-dimer and c reactive protein (crp), and the extent of thrombosis before and after the intervention (as secondary outcomes) were compared between groups. 2.5. statistical analysis according to literature, and considering an improvement rate of 0.33-0.65, and using the g power software, the minimum of 38 patients were allocated to each group; but with considering the dropouts, 208 patients were set out to be examined. statistical analysis was done using ibm spss statistics 25. continuous variables are described as mean and standard deviation (sd). categorical variables are described by frequency and percentage. gender and baseline calf swelling were compared between the four groups using chisquare. one-way anova analysis was used for comparison of age, bmi, crp, and d-dimer between the 4 groups. oneway anova analysis was used to investigate the changes in level of crp, d-dimer, and calf swelling after 3 months. also post hoc analysis using one-way anova was used to determine the significance of difference between study arms. p value < 0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of patients 208 patients (52 patients in each group) with unilateral dvt of lower limbs (62.8% right leg) were included in the study (23% had concomitant pte). during the trial, there were 26 dropouts due to reasons such as death, cancer, and inability to follow up and ultimately 182 patients (50 in warfarin group, 49 warfarin + rosuvastatin, 44 in rivaroxaban and 39 in rivaroxaban + rosuvastatin) finished the trial period (51.64% male). the baseline characteristics of studied patients are shown in table 1. among the patients, 54 (29.6%) had dvt in the area above the knee (the popliteal area) and 128 (70.4%) had dvt in the area below the knee. there was no significant difference between the groups in the baseline characteristics at the beginning of the study. five patients had iliac involvement (very proximal dvt), two in the rivaroxaban + rosuvastatin group and one in each of the other groups (p = 0.28). 42.8% of the patients had crp above the normal range (6 mg/l) on presentation. 3.2. outcomes table 2 shows the changes in crp, d-dimer, and calf swelling after 3 months in each study arm. post hoc analysis of the groups is presented in table 3 and details are given below: occurrence of pts based on the brandjes score, 31 (17.03%) patients had pts at the end of the study (table 4). the occurrence of pts was significantly lower in the groups taking statins (p<0.0001). in addition, no one in the statin groups had severe pts. calf swelling difference > 3 cm at the beginning of the study 140 (76.9%) patients had more than 3 cm difference in circumference diameter between two legs, 24 (17.1%) of which had differences more than 5 cm. after 3 months of treatment, in 47 (33.5%) patients the difference between circumference diameter of the two calves did not reach normal level (below 2 cm). although the change in legs circumference diameter before and after intervention was significant in all groups (p < 0.05), the differences were more prominent in groups 2 and 4 (p < 0.0001). the maximum change of circumference diameter was seen in patients with more than 5cm difference between 2 calves at base and those who were in statin groups. crp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. pishgahi et al. 4 table 1: comparing the baseline characteristics of patients between groups variables study groups p 1 (n = 50) 2 (n = 49) 3 (n = 44) 4 (n = 39) gender male 27 (54.0) 25 (51.0) 23 (52.3) 19 (48.7) 0.94 female 23(46.0) 24 (49.0) 21 (47.7) 20 (51.3) age (years) mean ± sd 55.01±4.3 54.04±3.9 56.53±4.4 55.2±4.6 0.06 body mass index (kg/m2) mean ± sd 30.30±3.2 29.71±3.2 30.09±3.2 30.54±3.3 0.68 crp (mg/l) mean ± sd 10.73±1.7 8.31±1.6 10.66±2.6 9.53±1.7 0.084 d-dimer (ng/ml) mean ± sd 3034.27±1230.1 3029.86±1471.9 2971.93±1730.8 3664.16±1964.6 0.176 calf size difference# > 3 cm number (%) 45 (90.0) 37 (75.5) 32 (72.7) 26 (66.7) 0.17 thrombose location n (%) above the knee 13 (26.0) 16 (32.7) 13 (29.5) 12 (30.8) 0.28 below the knee 37 (74.0) 33 (67.3) 31 (70.5) 27 (69.2) #: compared with unaffected limb. data are presented as mean ± standard deviation (sd) or frequency (%). group 1: warfarin; group 2: warfarin + rosuvastatin; group 3: rivaroxaban; group 4: rivaroxaban + rosuvastatin. crp: c-reactive protein. table 2: comparing the studied outcomes before and 3 months after intervention variable before after p value c-reactive protein (mg/l) warfarin 11.58±8.3 8.35±2.1 0.09 warfarin + rosuvastatin 8.53±3.3 2.24±0.4 0.001 rivaroxaban 11.69±8.6 7.69±3.2 0.07 rivaroxaban + rosuvastatin 9.78±4.1 1.62±0.5 0.001 d-dimer (ng/ml) warfarin 3034.27±1230.1 344.54±81.0 <0.0001 warfarin + rosuvastatin 3029.86±1471.9 148.48±61.1 <0.0001 rivaroxaban 2971.93±1730.8 345.33±143.7 <0.0001 rivaroxaban + rosuvastatin 3664.16±1964.6 217.83±134.1 <0.0001 calf swelling difference > 3# cm warfarin 45 (90.0) 23 (4.0) 0.04 warfarin + rosuvastatin 37 (75.5) 8 (16.3) <0.0001 rivaroxaban 32 (72.7) 11 (25.0) 0.01 rivaroxaban + rosuvastatin 26 (66.7) 5 (12.8) <0.0001 #: compared with unaffected limb. data are presented as mean ± standard deviation (sd) or frequency (%). after 3 months of medication use, serum crp levels were reduced in all 4 groups of the study but was only significant in groups 2 and 4 (p = 0.001 in both groups). in 11% (20 patients) although the crp had reduced, it had not reached the normal level (below 6 mg/l). according to table 3, post hoc analysis revealed that rivaroxaban + rosuvastatin group had more reduction than warfarin + rosuvastatin group (p = 0.84). d-dimer after 3 months of treatment, serum d-dimer was reduced in all patients but did not reach the normal level (below 500ng/ml) in 8% of them. between the patients with the serum d-dimer level above 10000 ng/ml, patients in the statin groups experienced significantly more reduction in ddimer levels than the other groups. in other words, statins were more efficacious in patients with higher levels of serum d-dimer (p<0.001) although the mean difference of d-dimer before and 3 months after intervention was statistically significant in all groups, the difference was greater in the rivaroxaban + rosuvastatin vs non-statin groups (p < 0.001) and warfarin + rosuvastatin (p = 0.017). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e43 figure 1: general scheme of study design. esrd: end-stage renal disease. 4. discussion the present study was conducted as a clinical trial with the aim of investigating the effect of the use of statins along with common anticoagulant therapy on the improvement of patients with acute dvt and reduction of pts incidence. the results show that the addition of statins to anticoagulants seems to make the regimen more effective in improving the treatment outcomes of dvt patients. moreover, rosuvastatin administration in combination with rivaroxaban or warfarin significantly reduces the amount of dvt-associated inflammatory factors including crp and d-dimer, compared to patients receiving anticoagulants alone. it can significantly reduce the incidence of pts and the difference in the size of the lower limbs within 3 months, which is even more effective when difference between two legs is more than 5 cm. statin use was associated with a decreased rate of dvt, pe, or overall vte in 7 studies (1 randomized clinical trial, 4 case–controlled studies, 1 retrospective cohort study, and 1 basic science study), including the jupiter trial. the large randomized trial of jupiter showed that in 17,802 patients, in 26 countries, with a 5-year follow-up, among people with normal ldl-c levels and elevated crp, rosuvastatin 20mg reduced the risk of vte by more than 40% compared with placebo (16). in two registrations based on the danish population, the use of statin among patients with vte diagnosis was associated with a lower risk of recurrent vte (hazard ratio (hr)= 0.74, and 95% confidence interval (ci) 0.680.87 and 0.72, 95% ci 0.580.88) compared with the group not consuming statin (17). adjuvant treatment with statins in patients admitted to the hospital with acute pe was also associated with a reduction in the risk of recurrent pe (hr= 0.50, and 95% ci 0.36-0.70) (18). the effect was maintained during and after stopping the anticoagulant therapy. in adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index m. pishgahi et al. 6 table 3: post hoc analysis using one-way analysis of variance (anova) to determine the significance of difference between study arms variable mean difference p value calf swelling difference > 3# cm rivaroxaban+ rosuvastatin reference warfarin -1.30342 <0.001 warfarin +rosuvastatin 0.73287* 0.06 rivaroxaban -1.08360* <0.001 change in c-reactive protein level rivaroxaban+ rosuvastatin reference warfarin -1.47436* .003 warfarin +rosuvastatin -0.32620 .864 rivaroxaban -1.74709* .000 change in d-dimer level rivaroxaban+ rosuvastatin reference warfarin -126.70677* <0.001 warfarin +rosuvastatin 69.35699* 0.017 rivaroxaban -127.49775* <0.001 occurrence of post thrombotic syndrome rivaroxaban+ rosuvastatin reference warfarin -1.25562* 0.034 warfarin +rosuvastatin -1.31674* 0.001 rivaroxaban -1.03977* 0.044 #: compared with unaffected limb. *: one-way anova. the difference seems to be significant between the rivaroxaban-rosuvastatin group and warfarin alone, or rivaroxaban alone. table 4: comparing the severity of post thrombotic syndrome (pts) based on brandjes score between the 4 studied groups severity of pts 1 (n =50) 2 (n = 49) 3 (n =44) 4 (n =39) p value mild (score ≤ 3) 6 (12.0) 5 (10.2) 4 (9.1) 4 (10.2) moderate (score= 4) 6 (12.0) 2 (4.1) 3 (6.8) 1 (2.5) < 0.0001 severe (score ≥5) 4 (8.0) 0 (0.0) 2 (4.5) 0 (0.0) data are presented as frequency (%). group 1: warfarin; group 2: warfarin + rosuvastatin; group 3: rivaroxaban; group 4: rivaroxaban + rosuvastatin. dition, there was a dose-response relationship in the effect of statin therapy. interpretation of these effects is however limited due to retrospective nature of the study. the results of existing studies have been controversial about the effect of rosuvastatin on incidence of pts. a multicenter randomized controlled pilot trial on 312 patients with acute dvt receiving standard anticoagulation has shown that the addition of rosuvastatin 20 mg once daily for 180 days, does not significantly decrease pts incidence (19). on the other hand, similar to our results, a randomized controlled trial including 230 patients with dvt, reported the reduction of pts incidence following rosovastatin administration. the results did not show significant differences in d-dimer levels following rosuvastatin administration in addition to low molecular weight heparin (lmwh); but patients who had received statin had significantly lower levels of crp and showed a significant decrease in pts incidence after 3 months of followup (11). in confirmation of these findings, various studies have shown that statin therapy, can reduce the level of plasminogen activator inhibitor-1 (pai-1) as a fibrinolytic inhibitor and the level of tissue factor as a coagulation cascade initiator (20, 21). decrease in the level of pai-1 or tf alone can increase net intravenous and intra-arterial clot fibrinolysis (22). the inhibitory mechanism of statins on tf consists of inhibiting synthesis of the isoprenoid mediator and in vitro inhibition of geranylgeranylation in the rho / rho kinase pathway (23). reducing the activation of the rho family reduces the expression of one of the key transcription factors called nf-kb; this transcription factor induces positive tf regulation. in addition, statins increase the expression of kruppel like factor 2 (klf2), a positive regulator of enos and thrombomodulin, and an inhibitor of tf and pai-1 (24). clinical and experimental studies also show that statins inhibit the activation of cyclooxygenase 1 (cox-1) and enhance the activity of nitric oxide synthase (nos), thereby reducing the activation and accumulation of platelets (25). results of this study also suggest a stronger protective effect against vte with rivaroxaban compared with warfarin. the effect of rivaroxaban on d-dimer levels was mentioned in other studies as well (26). rivaroxaban, as an inhibitor of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e43 factor xa, disrupts the intrinsic and external pathways of coagulation cascade, and ultimately inhibits the formation of thrombin, subsequent fibrinolysis, and the production of ddimer (27). d-dimer not only acts as an indicator of thrombotic activity, but also correlates to the size and the burden of the thrombosis (28). due to the 8-hour half-life of d-dimer (25), reduction of d-dimer levels during the first 24 hours of drug therapy is expected. similar effects was seen with other anticoagulants, including heparin, warfarin and apixaban (27). however, data seems to be more robust for rivaroxaban. in a study by utne et al., rivaroxaban showed an absolute 14% reduction of pts two years after an acute dvt episode and also improved quality of life compared to treatment with warfarin. it was suggested that the effect of rivaroxaban on pts is related to its rapid time to peak concentration and its stable anticoagulation effect. rivaroxaban’s other properties such as its binding and inhibition of the thrombus bound factor x can also be involved in this effect (29). another suggested mechanism is the involvement of residual vein thrombosis as a main factor in the development of pts. in a study by prandoni et al., residual vein thrombosis formation in patients with proximal dvt was compared between direct oral anticoagulants (doacs) and vitamin k antagonists (vkas) after three and/or six months. doacs showed more protective effect against residual vein thrombosis compared with vkas (41% and 21% after 3 and six months respectively, vs 52.3% and 54.5%) (30). in another study by cheung et al., rivaroxaban showed a numerically lower but statistically non-significant risk of pts compared to enoxaparin/vka treatment in acute dvt patients. non adherence when using vkas was suggested as the main reason for better long term clinical outcomes regarding pts when using rivaroxaban compared to vkas (31). regarding controversial results of studies on rosuvastatin adjuvant therapy, the anticoagulant used for the treatment may affect the incidence of pts. the results of our study show a more significant difference for pts incidence between the administration of rivaroxaban+rosuvastatin with warfarin alone or warfarin+rosuvastatin compared to rivaroxaban alone; which may propose the hypothesis of the synergistic effect of rivaroxaban and rosuvastatin for pts prevention. 5. limitations the strength of our study is that besides investigating the effect of rosuvastatin, the effect of two types of anticoagulants with and without rosuvastatin was. so far, no study has investigated the effect of rosuvastatin alongside rivaroxaban and compared rivaroxaban and warfarin in this context. our study has several limitations. first, the trial was not aimed to study the effects of rivaroxaban. second, a single ultrasound sonographer was used for sonography, therefore having a second opinion might change results. third, the same brand of rosuvastatin was used for all groups (rosurexin, actoverco), the issue of bias in the results can be raised, of course, the pharmaceutical company had no involvement in the study and interpretation of the results, and only supplied the drug. 6. conclusion the addition of rosuvastatin to anticoagulants seems to be effective in improving the treatment outcomes of dvt patients. rosuvastatin administration in combination with rivaroxaban or warfarin significantly reduces the level of inflammatory factors including crp and d-dimer, compared to patients receiving anticoagulants alone. furthermore, it can significantly reduce the incidence of pts and the difference in the size of the lower limbs within 3 months. 7. declarations 7.1. acknowledgments we would like to thank actoverco pharmaceutical factory, karaj, iran for supplying rosuvastatin for participants. 7.2. conflict of interest statement for decreasing the risk of potential bias actoverco pharmaceutical factory had no involvement in the study and interpretation of the results, and only supplied rosuvastatin. 7.3. fundings this study has been funded by shahid beheshti university of medical sciences; also, actoverco pharmaceutical factory supplied rosuvastatin. 7.4. authors’ contribution mp and rb: designed the study. rl and zt: collected the data. kkt 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direct oral anticoagulants. thromb res. 2017;153:97-100. 31. cheung yw, middeldorp s, prins mh, pap af, lensing aw, arina j, et al. post-thrombotic syndrome in patients treated with rivaroxaban or enoxaparin/vitamin k antagonists for acute deep-vein thrombosis. j. thromb. haemost. 2016;116(10):733-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion limitations conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 117 emergency (2015); 3 (3): 117-119 case report pharyngeal aspiration of complete upper denture in 90-year-old man; a case report mehrdad haghighi, simin dokht shoaei* clinical research and development center, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran *corresponding author: simin dokht shoaei, clinical research and development center, imam hossein hospital, tehran, iran tel: 982177585856 ext 2082; fax: +98 02177557069; email: drsimin2@yahoo.com received: december 2014; accepted: february 2015 abstract foreign body aspiration is unusual in adults, except those who are debilitated or have neuropsychiatric disorders. it can be a life-threatening situation and it often requires a high index of suspicion, because the diagnosis can be obscure. prompt diagnosis and intervention through foreign body retrieval are critical to prevent significant morbidity and mortality. we present a case of denture aspiration by a debilitated 90 years old man. he had aspirated his complete upper denture to pharynx causing incomplete obstruction with pleasure whistling respiratory sound, dyspnea, dysphagia and dysphonia. he underwent successful retrieval of the dental plate manually by fingers with complete resolution of symptoms. key words: pharyngeal; aspiration; foreign body; case report cite this article as: haghighi m, shoaei sd. pharyngeal aspiration of complete upper denture in 90-year-old man; a case report. emergency. 2015;3(3):117-19 introduction: oreign body aspiration can be a life-threatening condition if the aspirated object is large enough to cause complete airway obstruction necessitating prompt intervention (1). however, the diagnosis may be delayed when the history is atypical or when clinical and radiologic findings are misleading or overlooked by the physician. in spite of that, nearly all pharyngeal and airway foreign bodies are considered as medical emergencies (2, 3). we are presenting an old man who aspirated a large foreign body and misdiagnosed as a case of aspiration pneumonia. case presentation: a 90-year-old man was brought to the emergency room due to acute onset of severe generalized weakness, sudden onset of dyspnea, pleasure whistling in respiration, acute dysphagia to both liquids and specially solids and inability to speak, from 2 days ago. he had one time vomiting at onset of the symptoms. he had medical history of achalasia, recurrent pneumonia in last months and head trauma 2 months ago with sub-arachnoids hemorrhage and several convulsions. on arrival to hospital, his vital sign were as oral temperature: 37.8°c, heart rate: 100/minute, respiratory rate: 16/minute, blood pressure: 100/80 mmhg with 95% oxygen saturation on room air. he was completely alert but could not talk. in physical exam except for severe cachexia and superficial ulcers on two forearms, there was no other finding. lung exam was incomplete due to severe illness and superficial respiration. he did not have stridor and wheezing! none of examiners noticed to his respiration with pleasure whistling and the history of losing his upper dental prosthesis from two days ago. posterior-anterior chest x-ray revealed bilateral consolidations with the most prominence in the right middle lobe (figure 1). chest computed tomography (ct) scan revealed the same finding as well as bilateral pleural effusion (figure 2). he was admitted to the infectious disease ward with diagnosis of aspiration pneumonia. in next day, his dyspnea guts worst so made the corresponding physician to take a lateral neck radiography (figure 3). a large foreign body was lodged above epiglottis between oropharynx and hypopharynx. on physical examination, his lost upper complete upper denture with 5 x 5 centimeter size was seen in his pharynx behind the tongue and was manually extracted with fingers. his three days dyspnea, whistling, inability to talk and dysphagia was dramatically improved. he was treated for aspiration pneumonia due to last convulsions and was discharged in a stable condition after one week. in third visit after two months, he had no alimentary and respiratory sign and symptoms with good condition. f this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com haghighi et al 118 figure 1: posterior-anterior chest x-ray of patient figure 2: axial chest computed tomography scan of patient figure 3: lateral neck x-ray of patient, white arrow shows aspirated dentures. discussion: adults account for only about 20% of the reported cases of foreign body aspiration and most of them are seen after the sixth or seventh decade of life, when airway protective mechanisms lose their proper function (4, 5). the clinical features of foreign-body aspiration in geriatric patients are usually more obscure than in non-geriatric adults, which may lead to long delay in diagnosis ranged from 1 month to 3 years (6). in the adult population, such aspiration is most commonly secondary to unconscious accidental ingestion during general anesthesia, sedation, intoxication, seizures or neurologic disorders affecting the oropharynx. foreign bodies have a tendency to lodge in the right main stem bronchus as it is more vertical and larger in diameter than the left main stem bronchus (3). clinical management of an aspirated foreign body includes early recognition, acute emergency interventions, supportive care, and preventive anticipatory guidance. the diagnosis of foreign body aspiration can be difficult, especially if the patient does not recall an aspiration episode. foreign body aspiration has variable clinical manifestations, ranging from trivial symptoms to irreversible lung damage and life-threatening infection, atelectasis, and massive hemoptysis. patients may present with a history of fever, breathlessness, or wheezing or with features of a non-resolving pneumonia. on physical examination, these patients may have decreased breath sounds on the side with the foreign body or localized wheezing, or they may be asymptomatic. the clinical triad consists of wheezing, coughing, and diminished or absent breath sounds that is considered to be diagnostic of foreign body aspiration can be present based on the size and site of foreign body (6, 7). although plain films may be interpreted as normal, radiopaque foreign bodies may be seen. on chest x-ray, unilateral hyperinflation, lobar or segmental atelectasis, and mediastinal shift, or pneumomediastinum may be evident (7, 8). many foreign bodies are incidentally seen on radiographic imaging ordered for symptoms mistakenly attributed to other medical conditions including asthma and unresolving recurrent pneumonia (9). if a diagnosis of foreign body aspiration is delayed, a retained foreign body may result in unresolving pneumonia, lung abscess, and bronchiectasis. also, formation of granulation tissue around the foreign body may occur and may resemble bronchogenic carcinoma (10). a ct scan is helpful in visualizing radiopaque foreign bodies and alveolar collapse. it can also demonstrate airway foreign bodies that are radiolucent on plain radiographs. ct scans can depict a foreign body within the lumen of the tracheobronchial tree and the 3dimensional position of the foreign body within the thorax (7). because foreign body aspiration can mimic other respiratory conditions, a high index of suspicion is necessary in all patients with pneumonia, atelectasis, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 119 emergency (2015); 3 (1): 117-119 or wheezing with an atypical course, especially in patients who are unresponsive to medical therapy (11). this case is one of the unusual cases of such a large foreign body aspiration that the diagnosis was delayed for about three days. he was too debilitated to say about his denture in pharynx and chest x-ray could not reveal the plate because it was made from a plastic material and had no radiopaque metal. conclusion: diagnosis of foreign body aspiration may be retarded because of nonspecific signs specially if there is no recollection of the episode. the physician may be suspicious of this condition, even if the patient history and imaging obscure the clinical picture and pay attention to present history well and do a complete physical examination. acknowledgments: none conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. mahmoud m, imam s, patel h, king m. foreign body aspiration of a dental bridge in the left main stem bronchus. case reports in medicine. 2012;2012. 2. safari s, karimi e, baratloo a, alavi-moghaddam m, kalantarimeibodi m. a 16-year-old girl with acute onset respiratory distress. emergency. 2014;2(1):pp. 50-2. 3. qureshi a, behzadi a. foreign-body aspiration in an adult. canadian journal of surgery. 2008;51(3):e69. 4. latifi h, alinejad v, niknejad e. foreign body aspiration-an experience in our community. hermes journal france. 2014;71(2):31-9. 5. bekele a. aerodigestive foreign bodies in adult ethiopian patients: a prospective study at tikur anbessa hospital, ethiopia. international journal of otolaryngology. 2014;2014. 6. lin l, lv l, wang y, zha x, tang f, liu x. the clinical features of foreign body aspiration into the lower airway in geriatric patients. clinical interventions in aging. 2014;9:1613. 7. baharloo f, veyckemans f, francis c, biettlot m-p, rodenstein do. tracheobronchial foreign bodiespresentation and management in children and adults. chest journal. 1999;115(5):1357-62. 8. philippakis ge, moustardas mp. left main bronchus foreign body masquerading as diaphragmatic hernia in an adult patient. international journal of surgery case reports. 2012;3(5):170-2. 9. boyd m, chatterjee a, chiles c, chin jr r. tracheobronchial foreign body aspiration in adults. southern medical journal. 2009;102(2):171-4. 10. aissaoui a, salem nh, chadly a. unusual foreign body aspiration as a cause of asphyxia in adults: an autopsy case report. the american journal of forensic medicine and pathology. 2012;33(3):284-5. 11. seth d, kamat dm, pansare m. foreign-body aspiration: a guide to early detection, optimal therapy. consultant for pediatricians. 2007;6(1):13-8. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 33 emergency (2015); 3 (1): 33-39 original research knowledge and attitude regarding organ donation among relatives of patients referred to the emergency department mahboob pouraghaei1, mohammad tagizadieh2, ali tagizadieh3, payman moharamzadeh1, samaneh esfahanian4, kavous shahsavari nia5* 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. department of pathalogy, tabriz branch, islamic azad university, tabriz, iran 3. critical care unit, tuberculosis and respiratory research center, tabriz university of medical sciences, tabriz, iran 4. department of medicine, islamic azad university, tabriz branch faculty of medicine, tabriz, iran 5. road traffic injury research center, tabriz university of medical sciences, tabriz, iran *corresponding author: kavous shahsavari nia; road traffic injury research center, tabriz university of medical sciences, sina hospital, azadi ave, tabriz, iran. tel/fax: +984115412101. email: kavous.shahsavari@yahoo.com received: august 2014; accepted: september 2014 abstract introduction: organ donation is one of the surviving procedures, which can increase the life expectancy of endstage patients. inappropriate beliefs and attitude of individuals to organ donation, their poor knowledge, and the socio-economic level are one of the most important barriers for organ donation. therefore, here knowledge and attitude levels among relatives of trauma patients regarding organ donation were evaluated. methods: this cross-sectional study was done on relatives of trauma patients referred to the emergency department of sina hospital, tabriz, iran, through 2013 to 2014. the questionnaire included parts of demographic data and socioeconomic situations as well as status of knowledge and attitude regarding organ donation. a score between 0-7 was belonged to each person based on his/her level of knowledge. attitude level had a score between 0 -12. chi square, fisher, and mann–whitney u test were performed to assess the relation between demographic variables and the level of knowledge and attitude. p<0.05 was considered as a significant level. results: 79 persons (57.1% male) with the mean age of 31.3±11.3 years were evaluated. 57 (73.1%) of subjects agreed with organ transplant. the main causes of disagreement among relatives regarding organ donation were dissatisfaction of the donor's relatives (25%) and religious issues (15%). 49 (62.02%) studied people had inappropriate attitude and 27 (34.2%) ones had good knowledge. male gender (or=5.87; 95%ci: 3.32-8.42; p=0.001) and self-employed job (or=7.78; 95%ci: 4.64-10.92; p=0.001) are independent factors associated with poor knowledge about organ donation. self-employed job (or=3.86; 95%ci: 1.41-6.11; p=0.009) and poor knowledge (or=15.3; 95%ci: 9.0321.57; p<0.001) were related to inappropriate attitude toward organ donation. conclusion: the present study showed that 73.1% of participants agreed with organ donation. the major causes of disagreements were dissatisfaction of other relatives and religious beliefs. 62.0% of the studied people had positive view regarding organ donation and 34.2% of them well informed about. the most important causative factors for poor knowledge in this context were male gender and self-employed occupation. in addition, poor knowledge and self-employed job were two factors associated with inappropriate attitude toward organ donation. key words: organ transplantation; knowledge; attitude; tissue donors; directed tissue donation cite this article as: pouraghaei m, tagizadieh m, tagizadieh a, moharamzadeh p, esfahanian s, shahsavari nia k. knowledge and attitude regarding organ donation among relatives of patients referred to the emergency department. emergency. 2015;3(1):33-9. introduction: rgan donation is one of the surviving procedures that with recent advances in technologies and immune system suppression lead to improve the life expectancy of end-stage patients (1, 2). such a progression and high rate of success cause to increase the request number of organ donation and waiting time for donation. this issue caused that about 10-25% of patients needed donation in waiting list died without receiving the organ (3, 4). in iran, organ donation has been performed from both cadaveric and living donor. the first kidney donation in iran was done in 1967. by 1988 all donations have been performed from living donors. the rule of cadaver donation was approved in o this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com pouraghaei et al 34 2000. the network of providing transplant organs in the country has been designed since deputy of certain diseases and organ donation in the ministry of health has been founded in 2002 (5, 6). brain-dead patients are the most important source of organ donation, because of ability to provide several organs from the same one. however, only 40% of brain-dead patients were subjected to organ donor groups (7); the main cause is the low level of families’ consent. in fact, the studies showed that 25-60% of society members disagreed with organ donation from themselves or one of their family members after brain-dead (8-12). the reason of this low rate arises from inappropriate beliefs and attitude of individuals to organ donation, their little knowledge, and the socio-economic status. based on the above-mentioned, knowledge and attitude of family members have a critical role in increasing the percent of organ donation. therefore, the present study was done with the goal of evaluating knowledge and attitude levels among relatives of trauma patients, regarding organ donation and its causative factors. methods: study design and setting this cross-sectional study was done on relatives of trauma patients referred to the emergency department of sina hospital, tabriz, iran, through november 2013 to march 2014. because multiple trauma is one of the most important causes of brain-dead which more happens among the youth, this group are considered as one of the best source of organ donation. before beginning the project, explanations regarding questionnaire and the aim of study were stated for participants and informed consent were given from them. the study protocol was confirmed by ethical committee of tabriz university of medical sciences and researchers were observed helsinki declaration during all the study period. it should be mentioned that participation in this project was optional and information of questionnaire kept as secret. subjects the studied population consisted of all relatives of multiple trauma patients who were referred to the emergency department of sina hospital, tabriz. exclusion criteria were disagreement from participation and disability of the person to talk and communicate. the sample size was estimated 77 persons with considering to previous studies (d=0.1, z=1.96, and p=0.7) (13). finally, 79 subjects were evaluated. data gathering the designed questionnaire for the present study was used for data gathering. the questionnaire included demographic data and socio-economic situation; 7 questions were related to appraise the knowledge of subjects about organ donation and 12 ones with the goal of assessing their attitude status. validity of the questionnaire were determined by factor analysis and principal components. to determine the reliability of different parts of the questionnaire, cronbach's alpha coefficient was used that 0.83 was obtained. questions of the questionnaire regarding knowledge and attitude are shown in table 2 and 3. outcomes in the present study, the knowledge and attitude of patients' relatives regarding organ donation were evaluated. a score between 0-7 was belonged to each person based on his/her level of knowledge (each true answer had 1 score). in addition, attitude level had a score between 0-12. it should be mentioned that false answer did not have negative score. finally, causative factors on table 1: demographic characteristics of subjects variable n (%) age 15-29 41 (51.9) 30-44 30 (38.0) 45-59 2 (2.5) >60 6 (7.6) gender male 44 (57.1) female 33 (42.9) marital status single 31 (39.7) married 47 (60.3) income low 28 (36.8) middle 48 (63.2) high 0 (0.0) religion shia 77 (97.4) sunni 1 (1.3) other 1 (1.3) number of child 0 37 (50.7) 1 20 (27.4) >1 16 (21.9) occupational status staff 34 (55.7) self-employed 27 (44.3) education under diploma 10 (13.7) diploma 21 (28.8) postgraduate diploma 7 (9.6) graduate 29 (39.7) post graduate 6 (8.2) relative first-degree 26 (57.8) second-degree 19 (42.2) type of first-degree relative father 8 (33.4) mother 6 (25.0) sister 5 (20.8) brother 5 (20.8) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 35 emergency (2015); 3 (1): 33-39 knowledge and attitude of subjects to organ donation were assessed. statistical analysis statistical analysis was done using stata 11.0. after presenting descriptive analysis of data, chisquare, fisher, and mann-whitney u tests were performed to assess the relation between demographic variables and the level of knowledge and attitude. for this purpose, knowledge status (poor and good) and attitude (appropriate and inappropriate) were categorized in two groups. for categorizing the median of society was used as a cut point that is a common method in classifying groups (14-16). then significant factors in univariate tests were entered to multivariate logistic regression model. with 95% confidence interval (ci) for the odds ratio (or), independent causative factors on knowledge and attitude of the participants to organ donation were appraised. p<0.05 was considered as a significant level. results: in this research, 79 persons were evaluated (57.1% male). the mean age of subjects was 31.3±11.3 years (age group of 15-92 years). demographic characteristics of these people are shown in table 1. in a polling it was determined that 57 (73.1%) of subjects agreed with organ donation. the main causes of disagreement among relatives regarding organ donation were lacking of relatives’ consent (25%) and religious issues (15%). it worth noting that among discontented persons 9 (45%) subjects stated that they agreed with receiving the organ by themselves while they disagreed with donation of their organ or their relatives own. 53 (75.7%) of participants disclaimed that they had enough knowledge about organ donation. the most important ways of informing were television (57.8%), newspapers and articles (15.6%), friends and colleagues (8.9%), and internet (8.9%), respectively. however, most of the persons (85.9%) were not aware from the laws of organ donation. 13 (17.1%) of studied people believed that organ donation is not ethically true and 25 (33.8%) of them disagreed with having organ donation card as voluntary. 13 (16.9%) of these persons did not accept organ donation as a therapeutic procedure. the status of knowledge and attitude of these people are presented in table 2 and 3. the mean score of attitude (with maximum 12 scores) for the subjects was 8.0±3.3, significantly higher among people who agree (p<0.0001). the similar difference was also observed regarding the knowledge level of people who agreed. the attitude score of 49 (62.02%) studied people was ≥8 (appropriate level), while knowledge score of only 27 (34.2%) ones was≥5 (good level). this issue showed that knowledge about organ donation in most of the participants was low. univariate analysis displayed that women (51.5%; p=0.002) and staffs (50.0%; p<0.001) had higher level of knowledge (p=0.002). in addition, higher education level (p=0.001) associated to increase the knowledge about organ donation (table 4). the attitude level of these persons only related to their table 2: knowledge of subjects regarding organ donation question yes no do you have enough knowledge regarding organ donation? 39 (50.6) 338 (49.4) do you know about the laws of organ donation? 11 (14.1) 67 (85.9) do you think organ donation is a treatment option? 64 (83.1) 13 (16.9) do you have any information about brain-dead? 48 (62.3) 29 (37.7) do you think that brain-dead is a certain method to determine death? 38 (50.7) 37 (49.3) do you have knowledge regarding the steps of organ donation? 24 (30.8) 54 (69.2) do you think that the age of organ donor and receiver is important? 62 (81.6) 14 (18.4) table 3: attitude of subjects regarding organ donation question yes no do you agree with organ donation? 57 (73.1) 21 (26.9) do you agree with organ donation from your relatives? 54 (69.8) 25 (31.6) do you agree with organ donation form non-relatives? 52 (65.8) 27 (34.2) do you think that organ donation is ethically true? 63 (82.9) 13(17.1) do you agree with having organ donation card as voluntary? 49 (66.2) 25 (33.8) do you agree with organ donation if you have beneficial interest? 12 (16.4) 61 (83.6) if you watch a television interview about organ donation with families of the donors, will you admire them? 67 (88.2) 9 (11.8) if you agree with organ donation, is its type important for you? 39 (52.0) 36 (48.0) do you think that with more cultural enrichment regarding organ donation, the attitude of people will be changed in this area? 67 (91.8) 6 (8.2) do you agree to donate your organs if you experience brain-dead? 52 (66.7) 26 (33.3) do you think someday you may need organ transplant? 51 (65.4) 27 (34.6) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com pouraghaei et al 36 education, occupation status (p=0.01), and level of knowledge (p<0.001) (table 5). the results of multivariate logistic regression are shown in table 6. as it can be seen, male gender (or=5.87; 95%ci: 3.32-8.42; p=0.001) and self-employed job (or=7.78; 95%ci: 4.6410.92; p=0.001) are independent factors that are associated with poor level of knowledge about organ donation. moreover, self-employed job (or=3.86; 95%ci: 1.41-6.11; p=0.009) and poor knowledge (or=15.3; 95%ci: 9.03-21.57; p<0.001) were two factors related to inappropriate attitude toward organ donation. discussion: the present research showed that 73.1% of the studied people agreed with organ donation. the main reasons of disagreement were lacking of consent among relatives and religious beliefs. it should be mentioned that 62.0% of participants had appropriate attitude to organ donation and 34.2% of them were well informed about. the most important factors of poor knowledge in this regard were male gender and self-employed job. furthermore, poor knowledge and self-employed job were two factors related to inappropriate attitude toward organ donation. as mentioned before, the most important source of organ donation is brain-dead people, but such a donation has some limitations. the first problem is disagreement of donor's relatives. secondly, some studies have shown that organ donation from living donors has more successful results than brain-dead. in other words, it causes that physicians encourage using donors who have the optimum conditions for organ donation, included young people and those who have higher education level (17, 18). these two limitations cause that organ donation from brain-dead people associates with some problems. one of the effective elements for solving this problem is improving the knowledge and attitude of the family or spouse of the brain-dead person regarding organ donation (8). in many cases, subjects are potentially proper for organ donation but because of disagreement of their family or relatives, it cannot be happened. indeed, applying some strategies to improve the level of knowledge and attitude of the society can be helpful in this area. of course, the role of wrong cultural and religious beliefs should not be ignored. clergymen have a critical role in encouraging people to organ donation both for living and brain-dead persons (9). one of the religious beliefs in east asia (countries like japan and china) is keeping the dead body intact for the life after death. that's why positive attitude of people in china and japan toward organ donation is too low in compare to other regions (19, 20). in this context, liu and colleagues by comparing chinese and japanese students established that only 35.9% of chinese society and 43.6% of japanese have desired attitude toward organ donation. they also revealed that family attitude has a key role in making such a decision (9). thus, cultural enrichment and change in legislation can be helpful to reach this goal, as its successfulness was displayed in japan. the law of table 4: relationship between knowledge of subjects and demographic variables variable knowledge status p good poor age 15-29 14 (34.2) 27 (65.8) 0.686 30-44 9 (30.0) 21 (70.0) 45-59 1 (50.0) 1 (50.0) >60 3 (50.0) 3 (50.0) gender male 8 (18.2) 36 (81.8) 0.002 female 17 (51.5) 16 (48.5) marital status single 11 (35.5) 20 (64.5) 0.90 married 16 (34.0) 31 (66.0) income low 12 (42.9) 16 (57.1) 0.22 middle 14 (29.2) 34 (70.8) high 0 (0.0) 0 (0.0) occupational status staff 17 (50.0) 17 (50.0) <0.001 self-employed 2 (7.4) 25 (92.6) education under diploma 1 (10.0) 9 (90.0) 0.001 diploma 4 (19.1) 17 (80.9) postgraduate diploma 2 (28.6) 5 (71.4) graduate 17 (58.6) 12 (41.4) post graduate 3 (50.0) 3 (50.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 37 emergency (2015); 3 (1): 33-39 table 5: relationship between attitude of subjects and demographic variables variable attitude status p appropriate inappropriate age 15-29 26 (63.4) 15 (36.6) 0.97 30-44 18 (60.0) 12 (40.0) 45-59 1 (50.0) 1 (50.0) >60 4 (66.7) 2 (33.3) gender male 26 (59.1) 18 (40.9) 0.69 female 21 (63.4) 12 (36.4) marital status single 18 (58.1) 13 (41.9) 0.61 married 30 (63.8) 17 (36.2) income low 15 (53.6) 13 (46.4) 0.19 middle 33 (68.8) 15 (31.2) high 0 (0.0) 0 (0.0) occupational status staff 27 (79.4) 7 (20.6) 0.01 self-employed 13 (48.2) 14 (51.8) education under diploma 6 (60.0) 4 (40.0) 0.01 diploma 9 (42.9) 12 (57.1) postgraduate diploma 4 (57.1) 3 (42.9) graduate 23 (79.3) 6 (20.7) post graduate 5 (83.3) 1 (16.7) knowledge level poor 25 (48.1) 27 (51.9) <0.001 good 24 (88.9) 3 (11.1) organ donation was approved in japan in 1997 but because of religious beliefs, the procedure of recognizing brain-dead had unique double standard. consequently, during 12 years (until 2009) only 86 brain-dead donors have been success to do organ donation. new organ transplant policies in japan led to perform 16 cases of organ donation from brain-dead donors during three months in 2009 (11, 21). in islamic countries like iran, religious beliefs are too deep to separate from social issues. therefore, religious aspect of organ donation is one of the main facets of approving the law and thus fatwa of clergymen have been presented to confirm this activity. in terms of these fatwas, organ donation in iran weather from a living or brain-dead person has been permitted but commercial interest of it strongly rejected. however, with such laws and fatwas some disagreements with organ donation have yet existed. recently, there are some staffs in treatment centers of iran to preparing the relatives of brain-dead people for organ donation and giving their consent; but most parts of these attempts are unsuccessful (22). one of the important problems is lacking enough knowledge and appropriate attitude in public society to organ donation. in this study, 62.0% of subjects had appropriate attitude to organ donation. also, khoddami-vishteh and others showed that 70% of studied teachers had consent to organ donation after brain-dead. the major causes of disagreement in this society were mistrust to the organ donation network and diagnostic criteria of brain-dead (1). in the study of shabanzadeh and others 75.6% of the nurses in intensive care unit (icu) had a good attitude regarding organ donation from braindead patients (23). sanavi et al. also stated that 85% of medical students had a positive view to donation of table 6: independent risk factors of poor knowledge and inappropriate attitudes regarding organ donation variable or 95% confidence interval p poor knowledge female gender 5.87 3.32-8.42 0.001 self-employed job 7.78 4.64-10.92 0.001 inappropriate attitude self-employed job 3.86 1.41-6.11 0.009 poor knowledge 15.3 9.03-21.57 <0.001 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com pouraghaei et al 38 their organ, while only 49.2% of them agreed with this proceeding regarding their relatives. in this project no relationship was seen between age, gender, education level and attitude toward organ donation (24). additionally, nasrollahzadeh et al. defined that 66.2% of nurses had a desirable view regarding organ donation of their family members after brain-dead (25). as it can be seen, the attitude of people about it was in a nearly proper level (60-85%). but, some resistances have still existed against organ donation that representative the complication and difficulty of making a decision in this regard for both the person and relatives. in this procedure knowledge, attitude, and self-confidence of physicians and personnel of icu, patients and their families, culture and rules, as well as religious and economic beliefs of the society are effective. it seems that public education programs for the society to increase their knowledge and positive attitude can make the trust in people regarding organ donation. self-reporting bias is one of the limitations in the present research. another limitation was the lack of presence other religions in this study based on which the role of religion on attitude of participants could not be evaluated. moreover, the low sample size was another limitation, but considering to the findings, at least power of the present project was 95%. therefore, low sample size seemingly had no effect on the results. conclusion: the present study showed that 73.1% of participants agreed with organ donation. the major causes of disagreements were lacking of consent among relatives and religious beliefs. 62.0% of the studied people had positive view regarding organ donation and 34.2% of them well informed about. the most important causative factors for poor knowledge in this context were male gender and self-employed occupation. in addition, poor knowledge and self-employed job were two factors associated with inappropriate attitude toward organ donation. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of sina hospital of tabriz, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. lefaucheur c, glotz d. desensitization protocols for organ transplantation. in: kirk ad, knechtle sj, larsen cp, madsen lc, pearson tc, webber sa, editors. textbook of organ transplantation. united state: john wiley & sons; 2014. p. 763-72. 2. peters tg. life or death: the issue of payment in cadaveric organ donation. jama. 1991;265(10):1302-5. 3. dejong w, franz h, wolfe s, et al. requesting organ donation: an interview study of donor and nondonor families. am j crit care. 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students, teachers and clergymen. int j prev med. 2013;4(5):557-64. 16. nasrollahzadeh d, kamangar f, aghcheli k, et al. opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of iran. br j cancer. 2008;98(11):1857-63. 17. martínez‐alarcón l, ríos a, conesa c, et al. attitude of kidney patients on the transplant waiting list toward related‐living donation. a reason for the scarce development of living donation in spain1. clin transplant. 2006;20(6):71924. 18. ríos a, cascales p, martínez l, et al. emigration from the british isles to southeastern spain: a study of attitudes toward organ donation. am j transplant. 2007;7(8):2020-30. 19. neuberger j, farber l, corrado m, o’dell c. living liver donation: a survey of the attitudes of the public in great britain. transplantation. 2003;76(8):1260-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 39 emergency (2015); 3 (1): 33-39 20. ríos a, ramírez p, rodríguez m, et al. attitude of hospital personnel faced with living liver donation in a spanish center with a living donor liver transplant program. liver transpl. 2007;13(7):1049-56. 21. aita k. japan approves brain death to increase donors: will it work? the lancet. 2009;374(9699):1403-4. 22. mousavi sr. ethical considerations related to organ transplantation and islamic law. int j surg. 2006;4(2):91-3. 23. shabanzadeh a, sadr s, ghafari a, nozari b, toushih m. organ and tissue donation knowledge among intensive care unit nurses. transplant proc. 2009;41(5):1480-2. 24. sanavi s, afshar r, lotfizadeh a, davati a. survey of medical students of shahed university in iran about attitude and willingness toward organ transplantation. transplant proc. 2009;41(5):1477-9. 25. nasrollahzadeh d, siavosh h, ghods a. intensive care unit nurses' attitudes and knowledge toward brain death and cadaveric renal transplantation in iran. transplant proc. 2003;35(7):2545-9. archives of academic emergency medicine. 2019; 7 (1): e51 le t t e r to ed i to r compression test for diagnosis of phalangeal fracture; a letter to editor naser mohamad karimi1, faeze zeinali.n2∗ 1. department of emergency medicine, shahid sadoughi university of medical sciences, yazd, iran. received: july 2019; accepted: august 2019; published online: 15 september 2019 cite this article as: mohamad karimi n, zeinali.n f. compression test for diagnosis of phalangeal fracture; a letter to editor. arch acad emerg med. 2019; 7(1): e51. physical examination is the most important procedure for examining traumatized patients and ruling out possible bone fractures. edema, deformity, ecchymosis, tenderness on trauma location, and limited bone movement are among the signs of fracture. the diagnosis is documented by plain radiography. the number of false positive cases in this test increase in the presence of soft tissue injury along with bone damage. in this case, a great number of x-rays will be taken daily and many patients will be exposed to radiation, unnecessarily (1). the question to be fully answered is whether all cases of trauma and pain require radiographs or not? in cases of suspicion to scaphoid bone fractures, scaphoid compression (compressing a patient’s thumb along the line of the first metacarpal bone) is used as a clinical test. this test is said to have sensitivity of 70.5%, specificity of 21.8%, and predictive value of 41.9% for diagnosing scaphoid bone fracture (2). given the similarities present in force transmission and creation of pain in both scaphoid bone and phalanges, we assessed the mentioned maneuver in a similar fashion for phalanges and investigated the value of “axially/longitudinally compressing a patient’s finger along the longitudinal line of phalanxes” as a test for predicting phalangeal bone fracture in patients with traumatized phalanges. in this study, 100 patients with direct blunt trauma to hand were examined. the mean age of patients was 31.18 ± 11.05 years (85% male). all patients underwent compression test and radiography. one emergency medicine physician and one radiologist interpreted the radiographies, separately. the total sensitivity and specificity of test were 0.673 (95% ci: 0.485 – 0.895) and 0.875 (95% ci: 0.987 – 0.692), respectively. sensitivity and specificity of test for diagnosis of proximal phalanx fracture were 100% and 100%, respectively. ∗corresponding author: faeze zeinali.n; emergency department, shahid sadoughi hospital, yazd, iran. tel: 00989132749231, email: f.zeinali@ssu.ac.ir our findings demonstrated that in the presence of fracture involving the whole width of phalange of each finger, the test will be positive. hence, this test enjoys a high predictive value for diagnosing bone fractures and it can be used to reduce the need for x-rays ordered for phalanges. of course, some exceptions ought to be clarified. regarding joints, 26 victims had pain and tenderness on phalangeal joints. however, only 5 of them felt severe pain on scaphoid compression test, while, interestingly, none of them had fractures on radiography. on the other hand, out of the 21 victims that had no pain during the examination, 3 had avulsion fracture (fx) in the radiography, which also involved the joint surface, slightly. this may be attributed to the point that this type of fracture does not involve all the width of the phalanx and is not located on the longitudinal axis of the bone and in the path of force transmission, so the patient does not feel any pain in this region. on the whole, it may be concluded that considering the presence of various types of soft tissues in the joint, such as joint capsule, synovial fluid, and tendons in the joint space, force transmission is not done completely; hence, this test is not of much diagnostic value in diagnosing joint damage. 1. appendix 1.1. acknowledgements dr. naser mohamad karimi: conceived and designed the analysis, collected the data and analysis. dr. faeze zeinali.n: performed the analysis, wrote the paper, and submitted. 1.2. author’s contribution dr. naser mohamad karimi: conceived and designed the analysis, collected the data and analysis. authors orcids faeze zeinali.n: 0000-0003-1524-3112 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. zeinali.n et al. 2 1.3. conflict of interest the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support there was no financial payment to the authors for this study. references 1. wall b, haylock r, jansen j, hillier m, hart d, shrimpton p. radiation risks from medical x-ray examinations as a function of the age and sex of the patient. health protection agency, centre for radiation, chemical and environmental hazards chilton, didcot oxfordshire ox11 0rq isbn. 2011:978-0. 2. esberger d. what value the scaphoid compression test? the journal of hand surgery: british & european volume. 1994;19(6):748-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 59 emergency (2015); 3 (2): 59-63 original research a randomized clinical trial of intravenous and intramuscular ketamine for pediatric procedural sedation and analgesia mohammad gharavifard1, behnaz boroumand reza zadeh2, hamid zamani moghadam2* 1. department of anesthesiology, mashhad university of medical sciences, iran. 2. department of emergency medicine, mashhad university of medical sciences, iran. *corresponding author: hamid zamani moghadam; department of emergency medicine, imam reza hospital, mashhad, iran. tel: 985138525312; email: zamanimh@mums.ac.ir received: august 2014; accepted: november 2014 abstract introduction: ketamine is an agent broadly used for pediatric procedural sedation and analgesia in emergency departments. it has been found to be safe and with a low risk of complications. choosing between intravenous (iv) and intramuscular (im) injections is a matter of concern, so we did a comparison between the two methods in terms of their efficacy and rate of complications. methods: this single-blind clinical trial recruited 240 children (age: three months to 15 years, weight > 5 kg), who underwent short and painful procedures at the emergency departments. they were randomly allocated to two groups of 120 patients to receive either iv or im ketamine with of 1.5 and 4 mg/kg doses, respectively. indications for use, dose, side effects, and efficacy of the medications as well as duration of the procedure and time to recovery were compared between the two groups. results: the mean age of the iv and im groups were 6.5 ± 3.6 and 3.05 ± 2.6 years, respectively (p < 0.001). the onset of action of ketamine was 1.7 ± 1.1 minutes in the iv group and 8.6 ± 3.1 in the im ones (p < 0.001). patients of the iv and im groups remained in optimal sedation for 20.6±12.0 and 37.2±11.8 minutes, respectively (p < 0.001) .time until emergency department discharge was 65.3 ± 36.9 minutes in the iv group and 72.2 ± 14.5 in the im group (p = 0.40) .ketamine had excellent and moderate efficacy in 66.7% and 32.5% of the iv group and 70.0% and 25.0% in the im group, respectively (p = 0.02). totally, 60.0% of iv group patients and 40.0% of im group experienced drug side effects (p = 0.21). need for rescue dose was significantly higher in iv group (26.7% vs. 10.0%; p < 0.001). finally, recovery was tranquil and comfortable in 88 patients (73.3%) of the iv group and 108 patients (90.0%) of the im group (p = 0.06). conclusion: we found that although the sedative and analgesic effects of im and iv ketamine are not significantly different, duration of effect and onset of action are more desirable in the iv group for suturing, fracture reduction, and foreign body removal. meanwhile, the im method can lead to lesser need of rescue doses. key words: ketamine; analgesia; sedation; injections, intramuscular; infusions, intravenous cite this article as: gharavifard m, boroumand reza zadeh b, zamani moghadam h. a randomized clinical trial of intravenous and intramuscular ketamine for pediatric procedural sedation and analgesia. emergency. 2015;3(2):59-63. introduction: etamine is an antagonist receptor of n-methyl-daspartate (nmda) and phencyclidine derivate sedative agent broadly used for pediatric procedural sedation and analgesia (psa) in emergency departments (1-3). rapid onset, relatively short-term effects, and excellent sedative and analgesic effects make it an appropriate choice for short and painful procedures. numerous clinical trial studies have approved ketamine as a desirable and safe medication with low risk of emergence phenomena (4-10). several studies in this field have compared two methods of intravenous (iv) and intramuscular (im) administration based on time until hospital discharge and the incidence rate of side effects (6, 11-13). however, the superiority of either iv or im application of the drug has been still under debate. choosing the route of administration depends on available factors such as: emergency department facilities, patient characteristics and comfort, and physician’s experience and preference, drug’s complications and side effects, and onset and duration of drug action (12-15). since few studies were done among iranian population in this regard, the present study was performed to identify the preferable route for using ketamine by comparing the efficacy and side effects of the above-mentioned methods. k this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com gharavifard et al 60 methods: study design and setting this single-blind clinical trial was conducted on three months to 15 years old children that weighted more than 5 kilograms, and required psa for short and painful emergency procedures, who were presented to the emergency departments of imam reza and hasheminejad hospitals, mashhad, iran. ethics committee of mashhad university of medical sciences confirmed the study protocol and researchers were committed to the principles of the helsinki declaration throughout the study period. before any intervention, administered medication and its complications were thoroughly explained for their parents and informed written consent was obtained from them. this trial is registered in iranian registry of clinical trial (irct) under number irct2014071218454n1. participants 240 children were recruited using convenience sampling. they were randomly allocated in two groups of 120 patients by using block randomization method. subjects with a history of allergy to ketamine, severe cardiovascular diseases, thyroid disorders, head injury, central nervous system (cns) disorders, glaucoma or acute globe injuries, history or evidence of psychosis, obstructive sleep apnea, active pulmonary diseases such as upper respiratory tract infection, tracheal stenosis or surgery, needed procedures associated with stimulation of posterior pharyngeal region, and those who were not willing to participate were excluded from the study. intervention sedation by ketamine was performed according to standard guidelines (14). pulse oximetry and cardiac monitoring were constantly performed before, during, and after sedation. a nurse, blinded to the intervention, was present by the side of the patients during the whole procedure and not only recorded the routine nursing observations and evaluations, but also any abnormal conditions until the patient recovered to his/her pre-procedure state. venipuncture was performed for all patients to ensure blindness of the nurses and physicians. the first group of patients received iv ketamine (1.5 mg/kg, infusion by 100 milliliter normal saline; maximum dose 200 mg), and the second took an im dose (4 mg/kg; maximum dose 200 mg). patients with an open airway and adequate oxygen saturation, who were awake or could be easily awakened with minimal stimulation, able to drink liquids, and returned to the baseline level of consciousness were considered eligible for discharging from the emergency department. outcomes the data regarding demographic characteristics, duration of the procedure, the medicine’s onset and duration of action, efficacy, side effects, and time until emergency department discharge were gathered for all participants. at the end of the procedure, a specialist, who was blinded to the intervention, rated the efficacy of medicine in pain management and sedation as excellent (full sedation, immobility, and analgesia during the whole procedure), moderate (slight movements due to pain without interfering in the procedure), and poor (movements associated with pain that interfered in the procedure). the patients' status was followed for at least one hour in the recovery room and the incidence of any adverse effects was recorded. children with restlessness or hallucinations were categorized as "recovery with agitation". in the absence of any side effects, the subjects were classified as "tranquil and comfortable". statistical analysis the sample size calculation was performed based on detection of clinically significant differences in the incidence of vomiting. in a previous study, vomiting occurred in 18.3% and 35.4% of patients in iv and im groups, respectively (11). with considering α = 0.05 and 80% power, 232 patients were needed to be enrolled. the collected data were entered to spss version 20.0 (spss inc., chicago, il, usa) and described by using mean and standard deviation, graphs and tables. variables without normal distribution and ordinal ones were analyzed through mann-whitney u test. chi-square test was also performed to compare qualitative variables between the two groups. for assessment of any difference between iv and im groups related to efficacy, side effects, duration of the procedure, time to recovery and time to discharge we used generalized linear model adjusted for baseline characteristics. p values less than 0.05 were statistically considered significant. results: the mean age of the iv and im groups were 6.5±3.6 and 3.05±2.6 years, respectively (p < 0.001). 80 (66.7%) and 60 (50.0%) cases were male in iv and im groups, respectively (p = 0.009). the mean weight of the iv and table 1: demographic characteristics of children receiving intravenous (iv) or intramuscular (im) ketamine characteristics group (%) p iv im age (years) 6.5 ± 3.6 3.05 ± 2.6 <0.001* gender male 80 (66.7) 60 (50.0) 0.009# female 40 (33.3) 60 (50.0) weight (kg) 2.3 ± 13 14.2 ± 8.6 <0.001* procedure suturing 81(67.5) 97 (81.0) 0.34# fracture reduction 21(17.5) 11 (9.0) foreign body removal 18 (15.0) 12 (10.0) values are number (%); *, based on mann-whitney u test; #, based on chi-squared test this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 61 emergency (2015); 3 (2): 59-63 im groups were 22.3 ± 13.0 and 14.2 ± 8.6 kilograms, respectively (p < 0.001). suturing, distal radius fracture reduction, and foreign body removal were performed for 178 (74.0%), 32 (13.5%), and 30 (12.5%) subjects, respectively (table 1). the onset of ketamine action was 1.7 ± 1.1 (range: 1 5) minutes in the iv group and 8.6 ± 3.1 (range: 5 15) in the im group (p < 0.001). patients of the iv and im groups remained in optimal sedation for 20.6 ± 12.0 (range: 6 45) and 37.2 ± 11.8 (range: 15 60) minutes, respectively (p < 0.001) .time until emergency department discharge was 65.3 ± 36.9 minutes in the iv group and 72.2±14.5 minutes in the im group (p = 0.40) (figure 1) .ketamine had excellent and moderate efficacy in 66.7% and 32.5% of the iv group and 70.0% and 25.0% in the im group, respectively (p = 0.02) (table 2). totally, 60.0% of iv group patients and 40.0% of im experienced drug side effects. after adjustment for age, gender, and weight there was no statistical significance (p = 0.21). nausea and vomiting were observed in 40 (33.3%) patients of the iv group and 18 (15.0%) patients of the im ones (p = 0.21). hallucinations were detected in 16 (13.1%) and 12 (10.0%) of the iv and im groups, respectively (p = 0.30). iv and im injections of ketamine resulted in agitation in 24 (20.0%) and 12 (10.0%) patients, respectively (p = 0.88). the frequency of respiratory depression was eight (6.8%) and 18 (15.0%) in the iv and im groups, respectively (p = 0.29). need to rescue dose was significantly higher in iv group (26.7% vs. 10.0%; p < 0.001) (table 2). finally, the recovery was tranquil and comfortable in 88 patients (73.3%) of the iv group and 108 patients (90.0%) of the im group (p = 0.06). discussion: the results of the present study showed that although the sedative and analgesic effects of im and iv ketamine were not significantly different, duration of effect and onset of action were more desirable in the iv group for suturing, fracture reduction, and foreign body removal. meanwhile, the im method led to fewer need to rescue doses. in general, because of no difference in side effects and recovery time between iv and im methods, it was suggested that iv infusion of ketamine might be safer and more effective than im injection for psa. in 2006, roback et al. compared the side effects, efficacy, and duration of sedation induced by iv and im injection of ketamine in patients required orthopedic procedures. while respiratory complications in the two groups were similar (8.3% in the iv group vs. 4.0% in the im group), the frequency of vomiting was higher in the im group (26.3% vs. 11.9%). moreover, the im administration of ketamine was associated with significantly lower levels of pain and higher duration of sedation compared to the iv route. the researchers concluded that although im injection of ketamine had better sedative properties compared to iv application, it was clearly accompanied by longer recovery and more vomiting (11). in spite of similar methodology, the findings of roback et al. were in contrast with ours. the mean onset of action was 1.67 minutes in the iv group and 8.65 minutes in the im group. in addition, mean time until emergency department discharge was 65.33 and 72.25 minutes in the above-mentioned groups, respectively. consequently, the iv method was more favorable based on both speed of onset of action and time spent in the emergency department. since the efficacy difference between the two table 2: outcome of children receiving intravenous (iv) or intramuscular (im) ketamine factor group odds ratio 95% ci p* iv im efficacy excellent 80 (66.7) 84 (70.0) ref ref moderate 39 (32.5) 30 (25.0) 1.5 0.8 3.0 0.24 poor 1 (0.8) 6 (5.0) 0.4 0.05 3.4 0.19 need to rescue dose no 88 (73.3) 108 (90) ref ref yes 32 (26.7) 12 (10.0) 5.8 2.5 -13.6 <0.001 recovery tranquil and comfortable 88 (73.3) 108 (90.0) ref ref brief agitation 32 (26.7) 12 (10.0) 2.0 0.9 4.8 0.06 side effects no side effects 48 (40.0) 72 (60.0) ref ref nausea and vomiting 40 (33.3) 18 (15.0) 1.6 0.8 3.5 0.21 hallucination 16 (33.3) 12 (10.0) 1.7 0.6 4.2 0.30 agitation 24 (20.0) 12 (10.0) 1.1 0.4 2.7 0.88 respiratory depression 8 (6.7) 18 (15.0) 0.5 0.1 1.8 0.29 total 72 (60.0) 48 (40.0) 1.5 0.8 2.7 0.21 values are number (%); *, based on generalized linear model adjusted for age, gender, and weight of patients; ci = confidence interval; ref = reference category this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com gharavifard et al 62 groups was not significant, no route of administration was favorable in terms of effectiveness (i.e. those causing optimal sedation and analgesia) .in evaluation of the side effects, we did not detect any significant difference between groups. unlike our findings, roback et al. suggested this side effect to be more frequent following im injections (11). in addition, in ramaswamy et al. study side effects were seen in 35% of the im group and 20% of the iv group. moreover, time until discharge after the injection was 21 minutes shorter in the iv group. however, time from the beginning of triage until discharging was similar in two groups. the time required for catheterization in the iv method was suggested to be responsible for such findings (13). nevertheless, as we did not consider the time required for venipuncture, similar results were obtained regarding time until discharge. in a review study in 2010, deasy et al. reported that iv ketamine injections were generally associated with fewer side effects and shorter duration of action compared to im administration of the medicine. they concluded that when it is performed by a skilled person, the iv method could induce sedation more effectively than the im method (16). another review study by green et al. in 2006 indicated shorter time until discharge and less efficacy following the iv injections of ketamine. however, the researchers state that selecting the best route of administration depends on the physician’s decision based on the conditions and facilities of the hospital, particularly the emergency department and skillfulness of the staff (12). as the two groups in the current study had no significant difference in terms of efficacy, we recommend the same criteria for selecting the appropriate method. on the other hand, racial and environmental factors might have influenced on the effectiveness and side effects of the medicine, too. the present study contained some limitations. because of difference in the method of administration, there was no possibility to blind the patient to the intervention, so the study was done as single-blind fashion. furthermore, although the person who gathered the data was not informed about the injection method, he might be aware of the group that underwent therapy during clinical assessments. thus, it could be possible to influence the blindness of the observer in some cases. to avoid such a problem, the observer was trained not to ask anything from the patient regarding therapeutic interventions. conclusion: it was found that although the sedative and analgesic effects of im and iv ketamine were not significantly different, duration of effect and onset of action were more desirable in the iv group for suturing, fracture reduction, and foreign body removal. meanwhile, using the im method can lead to lesser need for rescue doses. acknowledgments: the authors appreciate the insightful cooperation of the staff of emergency department of imam reza hospital, mashhad, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. majidinejad s, esmailian m, emadi m. comparison of intravenous ketamine with morphine in pain relief of long bones fractures: a double-blind randomized clinical trial. emergency. 2014;2(2):77-80. 2. hosseini m, karami z, janzadenh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. emergency. 2014;2(4):151-7. 3. azizkhani r, kanani s, sharifi a, golshahi k, masoumi b, ahmadi o. oral chloral hydrate compare with rectal thiopental in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;2(2):85-9. 4. krauss b, green sm. procedural sedation and analgesia in children. the lancet. 2006;367(9512):766-80. 5. sahyoun c, krauss b. clinical implications of pharmacokinetics and pharmacodynamics of procedural sedation agents in children. curr opin pediatr. 2012;24(2):225-32. 6. green sm, rothrock sg, harris t, hopkins ga, garrett w, sherwin t. intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases. acad emerg med. 1998;5(10):971-6. 7. acworth j, purdie d, clark r. intravenous ketamine plus midazolam is superior to intranasal midazolam for emergency paediatric procedural sedation. emerg med j. 2001;18(1):3945. 8. mcglone r, howes m, joshi m. the lancaster experience of 2.0 to 2.5 mg/kg intramuscular ketamine for paediatric sedation: 501 cases and analysis. emerg med j. figure 1: comparing intravenous (iv) and intramuscular (im) ketamine injections based on onset of action, duration of effect, and efficacy in children presenting in the emergency department. *, significant difference based on generalized linear model adjusted for age, gender, and weight of patients. * * 0 10 20 30 40 50 60 70 80 onset of action duration of effect time to discharge t im e ( m in u te ) iv im this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 63 emergency (2015); 3 (2): 59-63 2004;21(3):290-5. 9. brown l, green sm, sherwin ts, et al. ketamine with and without atropine: what's the risk of excessive salivation? acad emerg med. 2003;10(5):482-3. 10. kashani p, yousefian s, amini a, heidari k, younesian s, hatamabadi hr. effect of intravenous ketamine in suicidal ideation in emergency department patients. emergency. 2014;2(1):36-9. 11. roback mg, wathen je, mackenzie t, bajaj l. a randomized, controlled trial of iv versus im ketamine for sedation of pediatric patients receiving emergency department orthopedic procedures. ann emerg med. 2006;48(5):605-12. 12. green sm, krauss b. should i give ketamine iv or im? ann emerg med. 2006;48(5):613-4. 13. ramaswamy p, babl fe, deasy c, sharwood ln. pediatric procedural sedation with ketamine: time to discharge after intramuscular versus intravenous administration. acad emerg med. 2009;16(2):101-7. 14. green sm, krauss b. clinical practice guideline for emergency department ketamine dissociative sedation in children. ann emerg med. 2004;44(5):460-71. 15. azizkhani r, esmailian m, shojaei a, golshani k. rectal thiopental versus intramuscular ketamine in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;3:[in press]. 16. deasy c, babl fe. intravenous vs intramuscular ketamine for pediatric procedural sedation by emergency medicine specialists: a review. paediatr anaesth. 2010;20(9):787-96. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 71 emergency (2014); 2 (2): 71-76 original research knowledge of emergency medicine residents in relation to prevention of tetanus hojjat derakhshanfar1, behrooz hashemi2*, mohammad manouchehrifar3, parvin kashani1 mohammad mehdi forouzanfar2 1. department of emergency medicine, imam hussein hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran abstract introduction: knowledge of emergency medicine residents about the management of patients suspected of having tetanus-favoring wounds is very important due to their responsibility for the treatment of such patients. the aim of the present study was to evaluate this knowledge and making sure of the adequacy of instructions they have received in relation to prevention of tetanus. methods: a reliable and reproducible questionnaire was used to evaluate knowledge of all the emergency medicine residents in imam hussein hospital in tehran, iran, about conditions favoring tetanus (9 questions) and proper interventions in such conditions (12 questions). the questionnaires were completed and scored as poor and good. the mann-whitney u test was used to analyze data. statistical significance was set at p<0.05. results: in the present study, 73 emergency medicine residents were evaluated (45.2% male). knowledge of 31 (42.5%) residents in relation to conditions favoring tetanus and 41 (56.2%) residents in correct therapeutic interventions was in good level. the most frequent incorrect answer was related to diabetic ulcers and wounds in patients with sepsis. there was an increase in scores of conditions favoring tetanus (p<0.001) and correct therapeutic interventions (p=0.001) with an increase in educational years. however, age (p=0.64), gender (p=0.31), job experience (p=0.38) and participation in educational courses (p=0.67) had no effect on the knowledge level of emergency medicine residents. conclusion: according to the findings of the present study, the knowledge of emergency medicine residents about correct management of patients suspected of tetanus was low, which emphasizes the necessity of providing further instructions on prevention of tetanus in wound management. key words: tetanus; vaccines; immunoglobulin; emergency medicine; primary prevention cite this article as: derakhshanfar h, hashemi h, manouchehrifar m, kashani k, forouzanfar mm. knowledge of emergency medicine residents in relation to prevention of tetanus. emergency. 2014;2(2):71-6. introduction:1 etanus is an acute and life-threatening condition which is common in all the age groups and in all the geographic locations. despite the fact that the condition is an international problem, hot and humid areas, which have a soil rich in organic materials, have the highest prevalence rate. in addition, the risk is higher in intravenous drug abusers, non-vaccinated individuals and immunocompromised patients (1). tetanusrelated mortality in developing counties is 135 folds higher than that in developed countries (2). the exact prevalence rate of the condition worldwide is not fully known, but based on estimates the incidence is 500,000 to 1,000,000 cases annually with a mortality rate of *corresponding author: behrouz hashemi; farhad rahmati; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel/fax: +982122721155; email: behrooz.hashemi@gmail.com received: 12 april 2014; accepted: 10 may 2014 20% to 45%. the majority of new tetanus cases arise in developing countries, with almost 50% of cases occurring in newborns. however, in developed counties, tetanus is rare and mostly occurs in the elderly (3, 4). it should be pointed out that tetanus is the only noncommunicable infections disease which can be prevented by vaccination (5). the most important risk factor for the development of tetanus is lack of immunization; in this context, 72% of tetanus victims have not completed their initial vaccination (6). in taking care of wounds suspected of tetanus and use of prophylaxis for it, a history of patient’s vaccination is very important because in individuals who have received five initial vaccination doses completely no particular intervention is necessary, except for cases in which the wound favours tetanus. however, if the patient’s vaccination history is not available or the vaccination has been incomplete, therapeutic interventions t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com derakhshanfar et al 72 are similar to those cases in which the patient is not immune to tetanus. in such cases, human tetanus immune globulin (tig) and booster vaccine are the most important therapeutic measures to prevent tetanus (7, 8). based on the above-mentioned, one of the measures, which is necessary in traumatic patients, is evaluation of their status and a judgment about the need to use tig and vaccine. the evaluation is carried out in different ways, including clinical judgment, elisa test and rapid diagnostic procedures (9-11). limitations in the use of laboratory tests and sometimes low accuracy of these tests (12, 13) have made the physician’s clinical judgment an important factor in decision-making processes. unfortunately, lack of proper knowledge of physicians in this respect has resulted in indiscriminate and unnecessary use of the vaccine and immune globulin (8, 12). this lack of knowledge has increased patient treatment costs and the economic toll on the country’s health system. on the other hand, if correct prophylactic measures are not taken in situations favouring tetanus, the patient is exposed to a high risk of this lifethreatening disease, which will have tragic consequences. therefore, the present study was undertaken to evaluate the knowledge of emergency medicine residents and the adequacy of education they have received in relation to prevention of tetanus. methods: the present cross-sectional study was carried out from april 2012 to october 2012 in imam hussein hospital in tehran, iran, a third-level university hospital with 60000 annual admissions. all the emergency medicine residents were evaluated. exclusion criterion was unwillingness to participate in the study. the minimum sample size at p=0.5 (14), maximum permissible error of 0.05 (d=0.05) at confidence interval of 95% was 61 residents. in order to collect data, a questionnaire was designed, with the aim to evaluate the knowledge of the emergency medicine residents about the diagnosis and management of wounds and conditions suspected of tetanus. the questionnaire was designed using emergency medicine references and textbooks under the supervision of two emergency medicine specialists and one epidemiologist. then the reliability of the questionnaire was confirmed by calculating cronbach’s alpha at 0.71. the questionnaire consisted of three sections. the first section consisted of questions on the residents’ demographic data (age, gender, educational status, job experience and participation in educational courses on tetanus). the second section consisted of nine questions, each with three choices (yes, no, i do not know) in relation to the knowledge of residents about conditions favoring tetanus. these nine questions concerned the odds of developing tetanus due to contaminated wounds, deep wounds, and wounds more than 12 hours old, wounds in systemic septic patients, diabetic ulcerations, infection of the injection site in drug addicts, wounds inflicted in open areas (streets, parks etc), burns, and finally wounds requiring surgical intervention for debridement. the third section consisted of 12 questions with three choices (always, sometimes, never) on the knowledge of residents about the necessary interventions in cases suspected of tetanus. these questions were as follows: two questions in relation to the necessary interventions concerning the time elapsed since the patient’s complete vaccination (more than 10 years, less than 10 years); administration of a booster dose in the past; lack of access to patient’s vaccination history; receiving only one dose of tetanus vaccine; and the necessary measures in immunocompromised patients. the questionnaires were handed in to the residents and each resident was given 30 minutes to answer the questions. scoring of the questions on the residents’ knowledge about conditions favouring tetanus was carried out by giving one positive score to each correct answer and one negative score to each incorrect answer. the answer “i do not know” received no score (a score of zero). in scoring questions on correct measures during encounter with conditions favouring tetanus, too, each correct answer received a positive score and each incorrect answer received a negative score. therefore, the subjects could receive a total score of -9 to 9 in the section on knowledge about conditions favouring tetanus and a total score of -12 to 12 in the section on correct intervention. a minimum score of 5 (5≥) in the section on conditions favouring tetanus and at least 6 (6≥) in the section on correct intervention were considered good knowledge level; scores less than these values were considered poor knowledge level. data collected from the questionnaires were entered into spss 21 software and then stata 11.0 software was used for descriptive and analytical evaluation of data. man-whitney u test was used to evaluate the relationship between the scores and the demographic data. statistical significance was set at p<0.05. results: in the present study, 73 emergency residents were evaluated (male: 45.2%). mean and standard deviation of ages of the subjects was 33.3±4.5 years. of 37 residents in the present study 29 (39.7%), 23 (31.5%) and 21 (28.8%) were first-, secondand third-year residents, respectively. the majority of the subjects (52.1%) had job experiences of more than two years, before initiation of residency. of all the residents under study, only 7 residents (9.6%) had participated in courses on tetanus and vaccination against tetanus (table 1). knowledge of 31 (42.5%) residents about the conditions favoring tetanus was at a good level (mean ± this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 73 emergency (2014); 2 (2): 71-76 sd = 3.2 ± 2.4). the most frequent incorrect answer was related to diabetic ulcers. despite the fact that such ulcers are not susceptible to tetanus, 46 residents (63%) believed it was; in contrast, 8 residents (11%) had no knowledge on the subject (“i do not know”). after diabetic ulcers, the most frequent incorrect answer was related to ulcers in patients with sepsis. although this ulcer is susceptible to tetanus, 3 residents (31.5%) believed it was not and 10 residents (5.5%) had no knowledge on the subject (“i do not know”). table 2 presents the frequencies of residents’ responses to each question separately. in addition, knowledge of only 41 (56.2%) residents about correct therapeutic measures was at a good level (mean ± sd = 6.1 ± 2.7). the most frequent mistake of residents was related to injection of tig in patients who have received complete vaccination. fifty-eight residents (79%) had given incorrect answer to the first question (elapsing of more than 10 years since complete vaccination) and 97 (50.7%) residents had given incorrect answer to the next question (elapsing of less than 10 years since complete vaccination). forty-three (58.9%) residents provided incorrect answers to question regarding necessity of tig and 38 (52%) necessity of vaccine in immune compromised patients (table 3). the only factor affecting the knowledge of residents about conditions favoring tetanus was the educational level of the residents (p<0.001), i.e. the residents’ knowledge increased with an increase in educational level. of first-, secondand third-year residents, 13.8%, 39.1% and 90.5% had good knowledge, respectively. however, other factors did not influence their knowledge about the conditions favoring tetanus. table 4 presents the relationship between these variables and the residents’ knowledge level. in addition, educational level affected knowledge about correct therapeutic measures (p=0.001). good knowledge level was higher (85.7%) in third-year residents than that in first-year (31.0%) and second-year (52.5%) residents (p=<0.001). however, age (p=0.64), gender (p=0.31), job experience (p=0.38) and participation in educational courses (p=0.67) had no effect on the knowledge level of emergency medicine residents (table 5). discussion: the results of the study showed that the knowledge of emergency medicine residents about the diagnosis of conditions favoring tetanus and correct measures in such cases was poor. the most important factor affecting this knowledge was educational years during residency, i.e. the third-year residents had higher knowledge compared to firstand second-year residents. the most common error of the residents in the diagnosis of conditions favoring tetanus was deeming diabetic foot ulcerations (63.0%), a factor leading to tetanus. on the other hand, the most common error in relation to therapeutic intervention for suspected ulcers was administration of tig in patients who have been completely vaccinated. in addition, 52.9% and 52% of residents were not aware about the necessity of administering tig and vaccine in immunocompromised patients, respectively. the results of the present study showed the necessity of providing further instructions for emergency medicine residents on the diagnosis and management of suspected tetanus cases. dabas et al showed that the knowledge of physicians in relation to the vaccination of adults was low and only 48.3% of physicians knew the correct indications and cases of tetanus vaccine (15). a study by brand et al, too, showed that 23% of cases suspected of tetanus were not treated correctly, with 6% of inadequate administration and 17% of excessive prophylactic measures against tetanus (16). a study by adeboye and sangowawa in britain, in which 40 emergency unit personnel, consisting of physicians and nurses were evaluated, showed that only 17 personnel (42.5%) were aware of new prophylactic guidelines against tetanus (17). a study by chowdhury et al showed that the majority of interns did not have sufficient knowledge about conditions favoring tetanus and proper therapeutic measures (18). a study by talan et al showed the inadequacy of the therapeutic measures in 35% of cases suspected of tetanus (19). as discussed above, awareness about conditions favoring tetanus and techniques used to tackle them have been at an unfavorable level in the majority of studies; based on these studies the prevalence of diagnostic and therapeutic errors in this disease condition is much higher than that in other clinical problems (12, 15, 1719). these funding show a great disparity between table 1: baseline characteristics of residents  variable frequency (%) gender male 33(45.2%) female 40(54.8%) educational status first year 29(39.7%) second year 31(31.5%) third year 21(28.8%) job experience less than a year 13(17.8%) 1-2 years 22(30.1%) more than 2 years 38(52.1%) participation in educational courses no 66(9.6%) yes 7(90.4%) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com derakhshanfar et al 74 these guidelines and what actual happens in the clinic. therefore, due to the low knowledge of residents in the present study and other similar studies, measures should be taken to define and prepare guidelines to promote awareness of physicians about prevention of tetanus. medical education groups, especially emergency medicine group, should play a key role in this respect because emergency medicine specialists, during their education and after graduation, are the first physicians who carry out therapeutic interventions (20, 21). in addition, the high prevalence of accidents and other cases of traumas in our country (22, 23) on one hand and the need to provide correct care for such traumas on the other hand show the great importance of proper and up-to-date knowledge of physicians in relation to the management of wounds. in the present study, irrespective of educational years, what attracts attention is the low scores of residents in the diagnosis and management of wounds favoring tetanus. as discussed in the results section, the means and standard deviations of the residents’ scores in the present study in relation to conditions favoring tetanus and correct therapeutic procedures were 3.2±2.4 and 6.1±2.7, respectively. based on these data, since the maximum attainable scores in these two sections were 9 and 12, respectively, unfortunately the scores gained by the residents were very low. these findings reflect the shortcomings of the educational system, which might be attributed to deficiencies of the educational structures, inappropriate educational environments, lack of attention of the educational system to the needs of the community and the students and finally presentation of a large volume of educational materials in a short time. therefore, different reasons have led to the inadequacy of the instructions provided, which include the inadequacy of the educational structure and system, inappropriate teaching environment and a lack of consistency between the educational programs and the table 2: answers given by the residents to questions on conditions favoring tetanus  questions is the wound susceptible to tetanus? (%) classification yes no i do not know deep wound 57 (78.1) 13 (17.8) 3 (4.1) susceptible contaminated wound 72 (8.6) 1 (1.4) 0 (0.0) susceptible wound older than 12 hours 47 (64.4) 22 (30.1) 4 (5.5) susceptible wound in sepsis patients 40 (54.8) 23 (31.5) 10 (5.5) susceptible diabetic ulcer 46 (63.0) 19 (26.0) 8 (11.0) not susceptible infection of injection site in drug addicts 55 (75.3) 11 (15.1) 7 (9.6) susceptible wounds produced in open environments 53 (72.6) 18 (24.7) 2 (2.7) not susceptible burns 68(93.2) 4 (5.5) 1 (1.4) susceptible wounds requiring debridement 50 (68.5) 17 (23.3) 6 (8.2) susceptible table 3: responses of residents in relation to correct measures in wounds favoring tetanus  questions on knowledge about correct measures always sometimes never classification 10 years elapsed after complete vaccination tig 34 (46.6) 24(32.9) 15 (20.5) never vaccine 67 (91.8) 6 (8.2) 0 (0.0) always <10 years elapsed after complete vaccination tig 9 (12.3) 28 (38.4) 36 (49.3) never vaccine 28 (38.4) 37 (50.7) 8 (10.9) sometimes complete vaccination plus a booster dose tig 3 (4.1) 20 (27.4) 50 (68.5) never vaccine 9 (12.3) 31 (42.5) 33 (45.2) sometimes no vaccination history is available tig 57 (78.1) 12 (16.4) 4 (5.5) always vaccine 70 (95.9) 3 (4.1) 0 (0.0) always one vaccination dose received tig 40 (54.8) 24 (32.9) 9 (12.3) always booster 58 (79.5) 10 (13.7) 5 (6.8) always immunocompromised tig 30 (41.1) 34 (46.6) 9 (12.3) always booster 35 (48.0) 30 (41.1) 8 (10.9) always *tig: tetanus immune globulin this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 75 emergency (2014); 2 (2): 71-76 needs of the community and the students. therefore, the existing educational system should be thoroughly revised. one of the limitations of the present study was the absence of an educational intervention. if an educational intervention had been available, it wound have been possible to evaluate the effect of education on improving the knowledge of residents. on the other hand, the resident’s awareness of the fact that he or she was under evaluation might have resulted in bias, affecting the results of the study, showing an increase in knowledge of residents in a false manner. however, since the mean knowledge level of the residents was low, the authors believe that the results are valid and reliable largely. nevertheless, it is suggested that in future studies, the emergency medicine residents’ knowledge be evaluated in a double-blind manner next to the patient bed and then an educational program be designed and the residents’ knowledge be evaluated again so that the effect of education on promoting knowledge can be evaluated. conclusion: according to the findings of the present study, the knowledge of emergency medicine residents about correct management of patients suspected of tetanus was low, which emphasizes the necessity of providing further instructions on prevention of tetanus in wound management. acknowledgments: the authors appreciate the insightful cooperation of medical sciences and the staffs of the emergency department of imam hussein hospital in tehran, iran. conflict of interest: table 4: the relationship between knowledge about tetanus risk factors and demographic factors  variable poor knowledge good knowledge p n % n % gender male 7 21.2 26 78.8 0.69 female 7 17.5 33 82.5 educational status first year 25 86.2 4 13.8 <0.0001 second year 14 60.9 9 39.1 third year 2 9.5 19 90.5 job experience less than a year 3 23.1 10 76.9 0.38 1-2 years 2 9.1 20 90.9 > 2 years 9 23.7 29 76.3 participation in educational courses no 12 18.2 54 81.8 0.61 yes 2 28.6 5 71.4 table 5: relationship between knowledge about correct therapeutic measure and demographic factors  variable poor knowledge good knowledge p n % n % gender male 10 30.3 23 69.7 0.31 female 8 20.0 32 80.0 educational status first year 20 69.0 9 31.0 0.001 second year 11 47.8 12 52.2 third year 3 14.3 18 85.7 job experience less than a year 4 30.8 9 69.2 0.38 1-2 years 4 18.2 18 81.85 > 2 years 10 26.3 28 73.7 participation in educational courses no 17 25.8 49 74.2 0.67 yes 1 14.3 6 85.75 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com derakhshanfar et al 76 none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. wassilak sg, kretsinger k. tetanus. bacterial infections of humans: springer; 2009. p. 813-32. 2. parveen g, hussain s, malik f, et al. seroepidemiological surveillance of antitetanus antibodies in 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downloaded from: www.jemerg.com 171 emergency (2016); 4 (4): 171-183 review article gastrointestinal headache; a narrative review majid t noghani1, hossein rezaeizadeh2, sayed mohammad baqer fazljoo3, mansoor keshavarz2,4* 1. department of iranian traditional medicine, faculty of medicine, shahed university, tehran, iran. 2. school of traditional medicine, tehran university of medical sciences, tehran, iran. 3. school of traditional medicine, tabriz university of medical sciences, tabriz, iran. 4. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. *corresponding author: mansoor keshavarz; department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. email: mkeshavarz@tums.ac.ir; tel/fax: +9821-66419484. received: july 2015; accepted: september 2015 abstract there are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. headache disorders are classified by the international headache society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (gerd), constipation, functional abdominal pain, inflammatory bowel syndrome (ibs), inflammatory bowel disorders (ibd), celiac disease, and helicobacter pylori (h. pylori) infection. some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. traditional persian physicians, namely ebn-e-sina (avicenna) and râzi (rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "participatory headache of gastric origin". we suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder. keywords: headache; migraine disorders; gastrointestinal diseases; medicine, traditional; headache disorders, primary; headache disorders, secondary cite this article as: noghani mt, rezaeizadeh h, fazljoo smb, keshavarz m. gastrointestinal headache; a narrative review. emergency. 2016;4(4):171-183 introduction: eadache is one of the common reasons for daily visits to emergency departments (ed). sadly, in some cases despite all the diagnostic and treatment measures, the cause of the headache cannot be determined and only symptoms are treated. in these cases, the patient experiences decreased quality of life and relapse, and therefore frequently revisits ed and neurologic clinics. the international headache society (ihs) released the second edition of the international classification of headache disorders (the ichd-ii) in 2004, and the ichd-iii (beta version) recently, with which various headache disorders are diagnosed by physicians throughout the globe. primary headaches, which are not considered to be attributed to another disorder are partly found to be cured or relieved by management of gastrointestinal (gi) abnormalities in the affected patients (1, 2). in the initial evaluations, some probable causes of headaches, such as gi disorders, are overlooked. providing evidence for primary headaches associated with gi disorders, may help classify this type of headache as a unique diagnostic entity. ancient persian physicians believed in a type of headache arising from disorders of the stomach and as an individual entity, described it in their writings as participatory headache of gastric origin or simply, “gastric headache” (3). we therefore, performed a review of the available literature to show the extent of the studies demonstrating the prevalence of headache and gi disorders’ coexistence, as well as studies proposing gi abnormalities as etiologies for headaches in which, treatments targeting the gi dysfunction relieved the headache. h mailto:mkeshavarz@tums.ac.ir this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com noghani et al 172 methods: review of the available literature from 1980 to july 2014, through a pubmed search was provided. searching the mesh terms “gastrointestinal diseases” or “migraine disorders” or “headache disorders” by the pubmed search builder altogether revealed roughly 900 articles. abstracts from pertinent articles were obtained. there were no language restrictions. if the study pointed to the association of any headache disorder with gi dysfunctions the paper was completely studied. in addition, bibilography and citations to the selected studies were evaluated and relevant articles not found previously were also included in order to augment the search results. in addition, a medline search was conducted using the keywords “iranian traditional medicine”, “persian medicine”, and “islamic medicine” and relevant papers were extracted. finally, principle texts of traditional persian medicine and the highly credited manuscripts on the subject of headache were studied. results: dyspepsia dyspepsia, defined as postprandial fullness, early satiety, or epigastric pain or burning by the rome committee, is reported to be present in a significant number of patients suffering from migraine (table 1). kurth et al. studied a population of migraineurs and compared them with a group of controls using a bowel disease questionnaire and reported pain centered in the upper abdomen to be significantly more frequent among patients with migraine (4). in another case-control study conducted by meucci et al. among dyspeptic patients, it was noted that this group of patients suffer significantly from migraine compared to the control group. it was suggested that dyspeptic patients of the dismotility-like or with nausea / vomiting referred for endoscopy be worked up for a diagnosis of migraine. given the completely normal endoscopic appearance seen in 90% of the migraineurs it was concluded that dyspeptic symptoms may be a consequence of the migraine (5). mavromichalis et al. however, demonstrated underlying inflammatory lesion in 29 of the 31 migraineurs undergoing endoscopy, supporting a causal link between gi inflammation and migraine. treatment targeting the gi tract resulted in relief of migraine (6). since the former two studies were not interventional, one could not conclude whether treatment of dyspepsia would have attenuated migraine headaches. however, sung hwang et al. demonstrated the resolution of headache in a group of children with epigastric pain or tenderness diagnosed with primary headache after initiating regular anti-acid medication (7). spierings reported a 50 year old dyspeptic male complaining of headache since early adulthood. patient`s dyspeptic symptoms were treated by cisapride 20 mg daily before dinner and subsequently the headache was almost completely resolved (2). interventional studies are needed to provide more evidence to support the concept that in at least some migraineurs, their dyspeptic symptoms are the cause of their headaches. gastroesophageal reflux disease gastroesophageal reflux disease (gerd), described as abnormal reflux of gastric contents into the esophagus resulting in symptoms or mucosal damage, may manifest with typical and atypical symptoms (8). however, among the extra-esophageal symptoms, headache is not pronounced as other atypical symptoms are. there is a growing body of literature demonstrating the association of headache with reflux symptoms (table 1). aamodt et al. performed the head-hunt study involving more than 43,000 individuals and reported reflux symptoms to be the most common symptom in this population with a rough prevalence of 30%. headache was noted to have a higher prevalence among individuals with much reflux symptoms compared to those without such complaints. in this study, patients suffering from headache were classified into migrainous and non-migrainous (9). in another study, katic et al. aimed to determine the prevalence of gerd and heartburn in a group of more than 1800 migraine patients. almost half of the migraineurs were reported to have gerd, heartburn, or related symptoms and this group suffered from more severe migraines and greater frequency of attacks (10). a population based study, enrolling close to 2000 individuals, reported significant correlation between headache and symptoms associated with gerd. it was noted that some patients’ headaches intensified with increased heartburn, and therefore, headaches were assumed to be a complication of gerd. the types of headaches, however, were not classified in this study (11). spierings reported two patients with headaches associated with reflux, in whom proton pump inhibitors resolved their headaches (1). further interventional studies targeting acid reflux suppression in patients affected by both disorders may be of benefit for understanding the causal relationship. constipation constipation is well known as a factor precipitating encephalopathy in patients with advanced liver disease. the mechanism involves retention of waste materials in the gut and reabsorption of toxic elements namely ammonia through blood circulation, reaching the brain and causing central nervous system (cns) dysfunction (12). however, when hepatic function is not compromised, the ammonia is cleared out of the circulation and therefore, constipation is not considered to cause any significant disturbance. on the other hand, there is evidence that constipation may be associated with headache, raising the question about the impact of constipation on cns even in the absence of advanced liver disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 173 emergency (2016); 4 (4): 171-183 t a b le 1 : g a st ro in te st in a l d is o rd e rs r e p o rt e d t o b e a ss o ci a te d w it h h e a d a ch e i n cl u d in g m ig ra in e s tu d y y e a r c o u n tr y s a m p le s iz e a g e g r o u p g e n d e r (f e m a le ) f in d in g s d y s p e p s ia m a v ro m ic h a li s e t a l. ( 1 3 ) 1 9 9 7 g re e ce 3 1 c h il d re n 5 8 .1 % t h e re i s ca u sa l li n k b e tw e e n r e cu rr e n t a b d o m in a l p a in a n d m ig ra in e . s p ie ri n g s* ( 1 ) 2 0 0 2 u s a 2 a d u lt 1 0 0 % t h e d y sp e p si a t ri g g e re d h e a d a ch e s. m e u cc i e t a l. ( 5 ) 2 0 0 5 it a ly 6 9 8 a d u lt 3 9 .2 % m ig ra in e i s a ss o ci a te d w it h d y sm o ti li ty -l ik e d y sp e p si a . p u cc i e t a l. ( 1 4 ) 2 0 0 5 it a ly 1 4 a d u lt 8 5 .7 % t h e re i s ca u sa l li n k b e tw e e n r e cu rr e n t a b d o m in a l p a in a n d m ig ra in e . a u ro ra e t a l. ( 1 5 ) 2 0 0 6 s w e d e n 2 0 a d u lt 7 5 % m ig ra in e s p a ti e n ts s u ff e r fr o m g a st ri c st a si s b o th d u ri n g a n d o u ts id e a n a cu te m ig ra in e a tt a ck . k u rt h e t a l. ( 4 ) 2 0 0 6 g e rm a n y 5 8 7 a d u lt 4 6 .5 % u p p e r a b d o m in a l sy m p to m s a re s ig n if ic a n tl y m o re f re q u e n t in p a ti e n ts w it h m ig ra in e c o m p a re d w it h h e a lt h y c o n tr o ls h w a n g e t a l. *( 7 ) 2 0 0 8 k o re a 5 8 c h il d re n 7 0 % t h e s tu d y s u p p o rt s a n y s p e ci fi c co rr e la ti o n b e tw e e n h e a d a ch e a n d e p ig a st ri c p a in o r te n d e rn e ss m o d ir i e t a l. ( 1 6 ) 2 0 1 2 u s a 8 4 a d u lt 8 2 .1 % h e a d a ch e s, e sp e ci a ll y m ig ra in e s, a re p re se n t in t w o -t h ir d s o f p a ti e n ts w it h g a st ro p a re si s. r e fl u x s y m p to m s s p ie ri n g s* ( 1 ) 2 0 0 2 u s a 2 a d u lt 1 0 0 % t h e r e fl u x t ri g g e re d h e a d a ch e s a n d r e sp o n d e d t o s p e ci fi c re fl u x t re a tm e n t. a a m o d t e t a l. ( 9 ) 2 0 0 8 n o rw a y 4 3 ,7 8 2 a d u lt / c h il d re n 6 3 .3 % t h e f in d in g m a y s u g g e st t h a t h e a d a ch e s u ff e re rs g e n e ra ll y a re p re d is p o se d t o r e fl u x . s a b e ri -f ir o o z i e t a l. (1 1 ) 2 0 0 7 ir a n 1 ,9 5 6 a d u lt 6 4 .8 % g a st ro e so p h a g e a l re fl u x d is e a se i s a ss o ci a te d w it h h e a d a ch e . k a ti c e t a l. ( 1 0 ) 2 0 0 9 u s a 1 ,8 3 2 a d u lt 7 3 % 2 2 .0 % o f m ig ra in e u rs r e p o rt e d h a v in g d ia g n o se d g e r d a n d 1 5 .8 % r e p o rt e d r e fl u x s y m p to m s. c o n s ti p a ti o n a a m o d t e t a l. ( 9 ) 2 0 0 8 n o rw a y 4 3 ,7 8 2 a d u lt / c h il d re n 6 3 .3 % t h e f in d in g s h o w e d p re v a le n ce o f th e m ig ra in e w a s h ig h e r in co n st ip a te p a ti e n ts . in a lo o e t a l. ( 1 7 ) 2 0 1 4 ir a n 3 2 6 c h il d re n 4 8 .2 % t h e s tu d y s h o w e d a s tr o n g c o rr e la ti o n b e tw e e n h e a d a ch e a n d ch ro n ic f u n ct io n a l co n st ip a ti o n p a rk e t a l. ( 1 8 ) 2 0 1 5 k o re a 1 6 8 c h il d re n 5 2 .1 % r e so lu ti o n o f co n st ip a ti o n i m p ro v e s h e a d a c h e i n m a n y p a ti e n ts d ia g n o se d w it h p ri m a ry h e a d a ch e *, s tu d ie s in w h ic h h e a d a ch e w a s re p o rt e d t o i m p ro v e o r re so lv e f o ll o w in g m a n a g e m e n t o f th e g i d is o rd e r. http://www.springerlink.com/content/?author=i.+mavromichalis this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com noghani et al 174 t a b le 1 : c o n ti n u e … s tu d y y e a r c o u n tr y s a m p le s iz e a g e g r o u p g e n d e r (f e m a le ) f in d in g s a b d o m in a l p a in a n tt il a e t a l. (1 9 ) 2 0 0 1 f in la n d 5 1 3 c h il d re n 4 9 .9 % c h il d re n w it h m ig ra in e a n d n o n m ig ra in o u s h e a d a ch e s re p o rt h ig h e r fr e q u e n ci e s o f a b d o m in a l p a in . g ro h o lt e t a l. (2 0 ) 2 0 0 3 n o rd ic co u n tr ie s 6 ,2 3 0 c h il d re n 4 6 .7 % t h e re w a s a n a ss o ci a ti o n b e tw e e n t h e a b d o m in a l p a in a n d i n ci d e n c e o f h e a d a ch e . b o cc ia e t a l. (2 1 ) 2 0 0 6 it a ly 6 0 c h il d re n 5 8 % m o st c h il d re n w it h m ig ra in e r e p o rt f g id s, a ss o ci a te d w it h a d e la y e d g a st ri c e m p ty in g w a lk e r e t a l. (2 2 ) 2 0 1 0 u s a 2 0 0 y o u n g a d u lt 6 2 % c h il d re n w it h a b d o m in a l p a in t h a t p e rs is ts i n to a d u lt h o o d m a y b e a t in cr e a se d r is k f o r h e a d a ch e . d e n g le rc ri sh e t a l. ( 2 3 ) 2 0 1 1 u s a 2 4 9 c h il d re n 6 7 .9 % c h il d re n w it h f u n ct io n a l a b d o m in a l p a in m a y i d e n ti fy a g ro u p t h a t is a t ri sk f o r h e a d a ch e l a te r in l if e . c h e li m sk y e t a l. ( 2 4 ) 2 0 1 2 u s a 3 8 c h il d re n 6 3 .2 % 4 0 % o f fu n ct io n a l g a st ro in te st in a l d is o rd e rs p a ti e n ts h a d m ig ra in e . in fl a m m a to r y b o w e l s y n d r o m e v a n d v ik e t a l. (2 5 ) 2 0 0 4 n o rw a y 2 0 8 a d u lt 6 7 % 4 4 .7 % o f p a ti e n ts w it h i rr it a b le b o w e l sy n d ro m e s u ff e r fr o m h e a d a ch e o r m ig ra in e . h e rs h fi e ld e t a l. ( 2 6 ) 2 0 0 5 c a n a d a 2 0 0 a d u lt 6 4 .5 % 4 7 % o f p a ti e n ts w it h i rr it a b le b o w e l sy n d ro m e h a v e h e a d a ch e . a g ra w a l e t a l. (2 7 ) 2 0 0 9 u k 2 1 1 o ld a d u lt 6 5 .2 % 5 0 % o f p a ti e n ts w it h i rr it a b le b o w e l sy n d ro m e s u ff e r fr o m h e a d a ch e . p a rk e t a l. ( 2 8 ) 2 0 1 3 k o re a 1 0 9 a d u lt 8 7 .2 4 0 .4 % o f m ig ra in e p a ti e n ts h a v e i rr it a b le b o w e l sy n d ro m e . in fl a m m a to r y b o w e l d is o r d e r s h e rs h fi e ld e t a l. ( 2 6 ) 2 0 0 5 c a n a d a 2 0 0 a d u lt 6 6 .5 % 1 9 % o f p a ti e n ts w it h i rr it a b le b o w e l sy n d ro m e s u ff e r fr o m h e a d a ch e . o li v ie ra e t a l. (2 9 ) 2 0 0 8 b ra z il 8 2 a d u lt 5 1 .2 % n e u ro lo g ic a l d is o rd e rs , su ch a s h e a d a ch e , a re c o m m o n i n i n fl a m m a to ry b o w e l d is e a se p a ti e n ts f o rd e t a l. (3 0 ) 2 0 0 9 u s a 1 0 0 a d u lt 7 7 % t h e p re v a le n ce o f m ig ra in e i n t h e i n fl a m m a to ry b o w e l d is e a se s a m p le w a s 3 0 % . m ig ra in e w a s m o re p re v a le n t in t h e c d s u b je ct s (3 6 % ) th a n u c s u b je ct s (1 4 .8 % ) d im it ro v a e t a l. ( 3 1 ) 2 0 1 3 u s a 5 0 2 a d u lt 6 7 .3 % m ig ra in e w a s m o re p re v a le n t in c e li a c d is e a se a n d i n fl a m m a to ry b o w e l d is e a se s u b je ct s th a n i n c o n tr o ls . *, s tu d ie s in w h ic h h e a d a ch e w a s re p o rt e d t o i m p ro v e o r re so lv e f o ll o w in g m a n a g e m e n t o f th e g i d is o rd e r. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 175 emergency (2016); 4 (4): 171-183 t a b le 1 : c o n ti n u e … s tu d y y e a r c o u n tr y s a m p le s iz e a g e g r o u p g e n d e r (f e m a le ) f in d in g s c e li a c d is e a s e s e rr a tr ic e e t a l. *( 3 2 ) 1 9 9 8 f ra n ce 1 a d u lt 1 0 0 % t re a tm e n t o f co e li a c d is e a se c o in ci d e d w it h t o ta l d is a p p e a ra n ce o f se v e re m ig ra in e a tt a ck s. s p in a e t a l. * (3 3 ) 2 0 0 0 it a ly 1 c h il d re n 1 0 0 % t re a tm e n t w it h t h re e m o n th s o f g lu te n f re e d ie t, i t w a s o b ta in e d t h e co m p le te r e so lu ti o n o f th e h e a d a ch e . r o ch e -h e rr e ro e t a l. ( 3 4 ) 2 0 0 0 s p a in 8 6 c h il d re n n r a n i n cr e a se d p re v a le n ce o f b o th m ig ra in e a n d t e n si o n h e a d a ch e s w a s o b se rv e d i n t h e c o e li a c p a ti e n ts . g a b ri e ll i e t a l. * (3 5 ) 2 0 0 3 it a ly 2 3 6 a d u lt 7 0 % d u ri n g t h e 6 m o n th s o f g lu te n f re e d ie t, o n e o f th e f o u r p a ti e n ts h a d n o m ig ra in e a tt a ck s, a n d t h e r e m a in in g t h re e p a ti e n ts e x p e ri e n ce d a n im p ro v e m e n t in f re q u e n cy . a le h a n e t a l. (3 6 ) 2 0 0 8 t u rk e y 2 0 0 c h il d re n 5 6 .2 % t h e re w a s a n a ss o ci a ti o n b e tw e e n m ig ra in e a n d c e li a c d is e a se . l io n e tt i e t a l. * (3 7 ) 2 0 0 9 it a ly 5 5 4 c h il d re n 6 7 .5 % t h e r e se a rc h e rs r e p o rt e d a h ig h f re q u e n cy o f h e a d a ch e s in p a ti e n ts w it h c e li a c d is e a se s. f ra n ca v il la e t a l. ( 3 8 ) 2 0 1 4 it a ly 1 5 c h il d re n 3 3 .3 % 2 0 % o f p a ti e n ts w it h c e li a c d is e a se s u ff e r fr o m h e a d a ch e . h e li c o b a c te r p y lo r i in fe c ti o n g a sb a rr in i e t a l. * (3 9 ) 1 9 9 7 it a ly 2 2 5 a d u lt n r h . p y lo ri i s co m m o n i n s u b je ct s w it h m ig ra in e . b a ct e ri u m e ra d ic a ti o n ca u se s a s ig n if ic a n t d e cr e a se i n a tt a ck s o f m ig ra in e . g a sb a rr in i e t a l. * (4 0 ) 1 9 9 8 it a ly 1 4 8 a d u lt 6 6 .4 % h . p y lo ri i n fe ct io n i s co m m o n i n p ri m a ry h e a d a ch e ; b a ct e ri u m e ra d ica ti o n a p p e a rs t o b e r e la te d t o a s ig n if ic a n t re d u ct io n i n c li n ic a l a tta ck s o f th e d is e a se t u n ca e t a l. * (4 1 ) 2 0 0 4 t u rk e y 1 2 0 c h il d re n 6 1 .7 % h e li co b a ct e r p y lo ri p o si ti v e n e ss i s m o re r e le v a n t in t h e m ig ra n o u s p a ti e n ts c o m p a re d w it h c o n tr o ls . y ia n n o p o u lo u e t a l. ( 4 2 ) 2 0 0 7 g re e ce 3 9 a d u lt 7 5 .5 % h . p y lo ri i n fe ct io n i s a p ro b a b le i n d e p e n d e n t e n v ir o n m e n ta l ri sk f a cto r fo r m ig ra in e w it h o u t a u ra . h o n g e t a l. * (4 3 ) 2 0 0 7 c h in a 5 0 a d u lt 4 2 % in te n si ty , d u ra ti o n , a n d f re q u e n cy o f a tt a ck s o f m ig ra in e w e re r e d u ce d a ft e r h . p y lo ri e ra d ic a ti o n . h o ss e in z a d e h e t a l. ( 4 4 ) 2 0 1 1 ir a n 1 4 0 a d u lt s 7 6 .5 % a ct iv e h . p y lo ri i n fe ct io n i s st ro n g ly r e la te d t o t h e o u tb re a k a n d s e v e ri ty o f m ig ra in e h e a d a ch e s. f a ra ji e t a l. * (4 5 ) 2 0 1 2 ir a n 6 4 a d u lt 7 3 .4 % h . p y lo ri e ra d ic a ti o n m a y h a v e a b e n e fi ci a l ro le o n m a n a g e m e n t o f m ig ra in e h e a d a ch e . a n sa ri e t a l. * (4 6 ) 2 0 1 5 ir a n 1 3 3 a d u lt n r h . p y lo ri e ra d ic a ti o n c o u ld b e a c u re o r to r e d u ce t h e s e v e ri ty a n d co u rs e o f m ig ra in e h e a d a ch e s. *, s tu d ie s in w h ic h h e a d a ch e w a s re p o rt e d t o i m p ro v e o r re so lv e f o ll o w in g m a n a g e m e n t o f th e g i d is o rd e r. n r : n o t re p o rt e d . this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com noghani et al 176 spierings reported a 47 year old female patient with chronic constipation complaining of headaches since adolescence. dietary change targeting the treatment of constipation reduced the frequency of the headaches (2). the head-hunt study further demonstrated this association and reported a higher prevalence of headache among individuals with much constipation compared with those without such a complaint (9). this suggests constipation to be considered in the context of and as a triggering factor for headaches including migraine. abdominal pain & inflammatory bowel syndrome headaches with migrainous features are reported in 40% of children with functional gastrointestinal disorders (fgid) (24). gi symptoms occurring during migraine attacks such as nausea or vomiting are well appreciated, but there is a growing body of evidence, which points to the occurrence of gi symptoms especially abdominal pain, outside the bouts of headaches (table 1). a population-based follow-up study investigated the comorbidity of other pains in 513 school-aged children with primary headache and found recurrent abdominal pain to be present in 50% of the patients (19). a large cross sectional study involving 6230 subjects evaluated the prevalence of recurrent complaints in various sites among 7-17 year-old population. the most common pain combination was reported to be headache and abdominal pain (20). boccia et al. determined the prevalence of fgids in migrainous children and found it to be present in 70% of the patients, among which functional abdominal pain (fap) comprised 35% of all. this population also suffered from prolonged total gastric emptying time. treatment with flunarizine significantly reduced the headaches and gi symptoms (21). fap in childhood is believed to persist into adulthood in nearly a third of the cases. one study reported that among those with unresolved fap, headaches are reported to be more prevalent compared to adults in whom childhood fap did not continue (22). in addition, children with fap have been shown to suffer more from headache and other non-gi somatic symptoms compared to healthy controls. more than one-third of these children go on to develop fgids at follow up as adolescents and adults (23). one of the most common fgids is ibs, which manifests with abdominal pain or discomfort and changes in bowel habits. the comorbidities of this disorder have been widely studied and it is now evident that patients with ibs suffer from a wide range of non-gi symptoms. one of the most appreciated comorbid non-gi symptoms is headache. it has been reported that 30-50% of patients with ibs, complain of headache (table 1) (25-28, 47, 48). on the other hand, up to 30% of migrainous patients are reported to suffer from ibs. these findings may be explained in two ways. either migraine or other primary headaches are not episodic diseases, but in fact they are disorders with underlying abnormality involving other systems that manifest with episodic attacks, or the headaches are manifestations or sequels of disorders in other body systems namely the gi tract. inflammatory bowel disorders migraine headaches have a higher prevalence in patients with ibd compared to that of the general population (30). dimitrova studied 111 patients with ibd 23% of which reported chronic headaches and this figure was significantly higher than controls (or = 2.66; 95% confidence interval [ci]: 1.08-6.54) (31). in brazil, a prospective study demonstrated headache to be the most common neurological complaint among 82 patients with ibd, 25% of which met the migraine criteria (29). generalized inflammatory response rather than isolated bowel inflammation may play the key role in the pathogenesis of the extra-intestinal manifestations of ibd (49). celiac disease also known as non-tropical sprue and gluten-sensitive enteropathy, celiac disease (cd) is now recognized as a multisystem autoimmune disorder characterized by inflammation of the small intestine caused by dietary gluten and related proteins in genetically susceptible individuals (50). after the publication of case reports introducing migraine as the first manifestation of cd and complete resolution of symptoms following gluten free diet (32, 33), many studies aimed at investigating the association of primary headaches with cd in children and adults (table 1) (34-38). recruiting 188 adult patients with cd and 25 with gluten sensitivity using an id-migraine tool, dimitrova reported chronic headaches to be present in 30% of celiac patients (or = 3.79; 95% ci: 1.78-8.10) and 56% of patients with non-celiac gluten sensitivity, but only in 14% of controls (p < 0.0001) (31). two studies involving pediatric cd patients were also conducted and similar results to adult studies were reported. in a case control study, contrary to the study performed previously (51), alehan et al. investigated the presence of tissue transglutaminase iga antibodies in a group of pediatric migraineurs and found it to be positive in 5.5% of the patients compared to 0.6% of the control group and the difference was statistically significant (36). in an interesting study, lionetti et al. retrospectively evaluated the prevalence of primary headache (based on the ihs criteria) in 354 children diagnosed with cd. in addition, they prospectively studied the prevalence of cd in a group of pediatric patients with primary headache. in the retrospective phase, they reported headache to be present in 25% of the patients before the diagnosis of cd, compared with eight percent of the control group (p < 0.001). in the prospective part, cd was diagnosed by the means of serology and biopsy in 5% of the patients compared with 0.6% of the general this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 177 emergency (2016); 4 (4): 171-183 population (p < 0.005). headaches were relieved (and in some completely resolved) after the institution of gfd in patients affected by both conditions (37). contradicting results have been recently reported in a study, which demonstrates the prevalence of cd in migraine children to be the same as in healthy controls. however, they also showed that gfd improved headaches in the group of children found to have cd (52). large multicentric studies may resolve these discrepancies. helicobacter pylori infection h. pylori infection is associated with various extradigestive diseases such as ischemic heart disease, primary raynaud phenomenon, primary headache, alopecia areata, and hepatic encephalopathy (53). gasbarrini et al. reported the association of h. pylori infection with primary headache and the improvement of symptoms with eradication of the bacteria (39, 40). contradictory results were reported afterwards (54, 55), however, more recent studies mainly using histological analysis of gastric mucosa biopsy for h. pylori detection have favored its pathogenic role in migraine (41-44). a double blind randomized clinical trial in 2012, reported the beneficial effects of h. pylori eradication in management of migraine patients (45). overall, regarding studies supporting a role for h. pylori in migraine it may be judicious to identify h. pylori infection in migraineurs by noninvasive means especially if suffering comorbid gi symptoms. pathophysiology the pathophysiology of headache disorders especially migraine and various gi abnormalities are widely studied individually. however, the scientific literature about mechanisms underlying the comorbidity of the two conditions is scant. few hypotheses exist aiming to explain the association of headache and gi disorders. central sensitization and parasympathetic referred pain: longstanding visceral afferent stimuli on convergent viscera-somatic neurons result in expansion of the receptive fields in size and number, decreased response thresholds, and amplification of response magnitude. this process leads to hyper-responsiveness of neurons within the cns to nociceptive and non-nociceptive stimuli, which is defined as central sensitization (56). dyspeptic migraineurs are shown to have postprandial hypersensitivity to gastric distention. it is postulated that this hypersensitivity in dyspeptic patients, results from abnormal processing of gastric stimuli at the level of the cns. this in turn activates the common pain network for both somatic and visceral pain, therefore causing headache (14). the “parasympathetic referred pain” theory is hypothesized for explaining the comorbidity of various gi disorders with headache including migraine. continuous stimulus ascending from visceral afferents leads to the central sensitization of trigeminocervical nuclear complex expressing a parasympathetic referred pain in the head (57). reflux of gastric contents into esophagus in gerd may be one example of chronic visceral stimulus leading to sensitization and referred headache. this theory may also be applicable for patients with ibs, who have various somatic complaints in addition to their gi symptoms. migraineurs and patients with ibs may have a very sensitive central and enteric nervous system, which have turned hypervigilant through time and may show exaggerated responses to unpleasant stimuli (58). serotonin: the neurotransmitter serotonin is present in the cns and in the nervous system within the gi tract. serotoninergic drugs are shown to have regulatory effects on gastric motility, and have been proven beneficial in migraine treatment and prophylaxis. serotonin hypothesis may therefore be another explanation for the comorbidity of headache and gi abnormalities such as dyspepsia and ibs (14, 59). serotoninergic pathways may represent the target for the treatment of patients suffering from both conditions. autonomic nervous system (ans) dysfunction: ans dysfunction is shown to be present in both headache and gi complaints. the role of ans is implicated in postprandial gastric accommodation, thus ans dysregulation may result in delayed gastric emptying and dismotility-like dyspepsia. in addition, migraineurs are demonstrated to suffer from chronic ans dysfunctions (4, 9, 60) and are noted to have gastric stasis even outside acute attacks (15, 16). this phenomena, however, may be more prominent in migraineurs with dyspeptic symptoms in the interictal period, but interictally symptom free patients, may have normal gastric morphology and accommodation (61-63). the ans also has a role in the pathopysiology of gerd in which the lower esophageal sphincter is hypotensive or has increased transient relaxations (10). calcitonin gene-related peptide (cgrp): cgrp is demonstrated to increase during migraine attacks (64-66). this neuropeptide is a potent vasodilator of intracranial vessels (67) and mediates pain transmission in the cns (68). infusion of this neuropeptide can induce migraine attack in migraineurs (69). the serotonin receptor agonist sumatriptan, which is administered to manage the acute bouts of migraine, is suggested to act partly by blocking the release of cgrp (70). in addition, this neurotransmitter helps to regulate gastric relaxations in response to ingestion of food or liquid. cgrp has been shown to have a role in disorders of the gastric reservoir functions leading to functional dyspepsia with anorexia and early satiety (4, 10). cgrp therefore, may have a role in the association of migraine and gi disorders. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com noghani et al 178 vasculopathy: vascular tone dysfunction and abnormal regional cerebral blood flow is demonstrated in migraineurs affected by cd or h. pylori (35, 37, 42, 71, 72). since cd arises from an autoimmune response against tissue transglutaminase it is postulated that the same interaction may take place against this enzyme within the brain vascular endothelium leading to various neurologic symptoms observed in patients with cd (36, 73, 74). this theory, however, may be more applicable for adults than pediatric patients (33). in h. pylori infection, the immune system interacts with the bacterium and vasoactive agents are released. it is hypothesized that this phenomenon may in turn lead to a systemic vasculopathy and alterations of vascular permeability in various sites including the intracranial arteries. this phenomenon along with the production of oxidants and nitric oxide results in regional cerebral blood flow changes; hence inducing migraine headaches (39, 42, 44). the role of oxidative stress however, has recently been questioned (75). food allergy: the role of food allergy in the activation of the immune system and subsequent inflammation has been the subject of study for decades (76). allergy to certain food antigens and the development of ige and igg antibodies may lead to an inflammation response which can play a role in the pathophysiology of migraine and ibs (77, 78). it is demonstrated that migraineurs are positive for igg food allergens more frequently than control subjects and their symptoms may improve with an elimination diet (79). in recent years, studies have focused on the iggbased elimination diet for migraineurs and also ibs patients and successful results have been reported in the attenuation of symptoms (80-82). this supports the theory that inflammation may play a key role in the pathophysiology of migraine and may help to explain the comorbidity of primary headaches and gi complaints. the “persian medicine” “traditional medicine is the sum of all the knowledge and practices used in diagnosis, prevention, and elimination of physical, mental, or social imbalance; relying exclusively on practical experience and observation handed down from generation to generation whether verbally or in writing” (83). traditional medicine (tm) is growing more and more popular worldwide (84). the affordability and accessibility of this system along with concerns regarding side effects of chemical drugs and management of chronic debilitating diseases such as cancer, diabetes, and heart disease has led many patients to become more interested in tm (85). the tm practiced in iran, called the “persian medicine” (pm), which is known as greeko-arabic (unani) medicine elsewhere (86) has a history of more than 8000 years (87). the underlying physiological concept in pm is that of the “humoral theory” which is in coordination with the teachings of the ancient greek scholars namely hippocrates (460-370 bc) and galen (129-199 ad). the humoral theory states that there are four types of basic particles from which all elements are made. they act on each other and finally make up the humors, which in turn constitute the body organs. thus, according to this theory, health results from the balance of humors within the body and their imbalance leads to disease. humors are four in number named "dam" (sanguis or blood), the quality of which is warm and moist, "balgham" (phlegm) which is cold and moist, "safra" (choler or yellow bile) which is warm and dry, and "soada" (melancholer or black bile) which is cold and dry (88, 89). medieval medical science was gathered by ancient physicians, the most influential of which were râzi (rhazes, 860-940 ad) and ebn-e-sina (avicenna, 980-1037 ad) and they added to that their own observations and experience (90). ebn-e-sina wrote more than 100 books in his short life span, 16 of which were on medicine (91). his masterpiece the “al-qanoon fi al-teb” (the canon of medicine) became the principle medical textbook and was taught and studied in universities of europe and asia from the twelfth century until the end of the seventeenth century (92). partly, statements in this book still have relevance today in different issues of health and disease (93-97). ebn-e-sina has described headache disorders and thoroughly discussed the etiology, pathophysiology, symptoms, and various treatments on this issue, in the third volume of the qanoon. in this book, headache disorders, referred to as "soada", are classified into 28 types with each having unique diagnostic criteria and treatment protocols. some types are classified as headaches originating from different organs which have neurovascular communications with the cns. one of the most important of these organs was believed to be the stomach, and gastric abnormalities were considered one of the most common etiologies for headache disorders in general (88). râzi also describes in his book the al-hawi (continents), a kind of headache originating from the stomach due to the production of bitter humors in the gastric fundus. symptoms aggravate during fasting especially after waking up in the morning (90). headaches originating from the stomach are classified into seven subtypes. these seven kinds of headache are described here in brief and their key symptoms, aggravating and relieving factors of each kind, are summarized in table 2. the first type is headache due to abnormal quality of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 179 emergency (2016); 4 (4): 171-183 humors within the stomach. excess warmth, cold, dryness, or moisture of the humors within the stomach may induce headaches. once the normal qualities are reestablished headache is relieved. imbalance of humors within the stomach comprises the second to fourth type. excess safra, balgham, or soada in the gastric cavity may lead to mucosal injury and gastric dysfunction. patients with headache due to excess soada may also present with manifestations of accumulation of soada within the cns and therefore, suffer from mood disorders. another type is headache due to the production of excess gas as a result of ingestion of gas producing foods such as leguminous seeds. in the first stages, patients may experience epigastric pain just before the initiation of headaches, and once the abdominal pain and bloating is resolved, the headache improves. the sixth type is headache due to the production of excess vapor in the stomach resulting from ingestion of certain kinds of vegetables capable of producing vapors after gastric digestion. the vapors were considered to ascend to the table 2: the seven types of headache arising from abnormalities within the stomach etiology key symptoms aggravating factors relieving factors treatmenta abnormal quality of humors headache occuring after heavy meals overeating eating less; prokinetics restoration of the normal quality excess safra (choler or yellow bile) nausea; anorexia; bitter taste in the mouth; excess thirst; subicteric sclera; epigastric burning starving; safra producing foodsb avoiding hunger; vomiting the excess safrac clearing the stomach from excessive humor excess balgham (phlegm) increased salivation; regurgitation; bloating; anorexia; decreased thirst overeating; balgham producing foodsd starving; vomiting the excess balgham; sleep; prokinetics clearing the stomach from excessive humor excess soada (melancholer or black bile) food craving; epigastric burning; regurgitation anxiety; depression; soada producing foodse relaxation; vomiting the excess soada clearing the stomach from excessive humor excess luminal gas frontal headaches; abdominal pain; bloating gas producing foods avoiding gas producing foods elimination of the excess gas excess vapors pounding headaches; vertigo; tinnitus vapor producing foods (onion, garlic, pepper, and spicy vegetables) avoiding vapor producing foods; consuming coriander after meals elimination of the excess vapor; blocking the ascent of vapors to the brain weakness of the gastric fundus and the cardia headache occurs during hunger especially when waking up in the morning; irritability starving; walking under the sun while hungry; malodorous smells avoiding hunger and having breakfast in time; avoiding cns stimulants; avoiding malodorous smells strengthening the fundus and the cardia a, treatment methods presented were carried out by appropriate foods and natural drugs. b, spicy and salty foods, foods fried in oil, eggs, nuts, grapes, coconut, honey. c, certain drugs were used to induce vomiting. patients experienced rapid relief of headache afterwards. d, fish, milk, yogurt, cheese, cucumber, tomato, lettuce, watermelon, strawberry, sour cherry, kiwi, drinking water with meals. e, beef, pork, fish, sausages, ham, eggplant, lentil, potato, mushroom, sour tasting fruits, barley, black tea, coffee. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com noghani et al 180 brain and induce headaches. patients may also experience anorexia, nausea, and indigestion following the ingestion of such vegetables (table 2). the seventh type is headache due to weakness of the gastric fundus. the fundus and the cardia have inadequate strength, gastric visceral sensory thresholds are decreased, and patients have gastric hypersensitivity. patients are also easily irritated in response to unpleasant stimuli (table 2). each of these seven subtypes of headache are clearly defined and thoroughly described by ancient scholars in medieval medical resources and treatment regarding each kind is provided (88, 98). the pathophysiology underlying these types of headache is explained in the context of the aristotle philosophy and the humoral theory. nevertheless, they may correspond to the neurovascular mechanisms postulated today for explaining the pathophysiology of headache disorders associated with gi abnormalities such as central sensitization, vasculopathy, and alterations in the regional cerebral perfusion. patients presenting with primary headache associated with gastric dysfunction (especially dyspepsia), if thoroughly questioned, may be recognized to fit in with one of the seven types of headache disorders above. if this is the case, then they may undergo remission with the institution of the appropriate treatment. this is exactly what is taking place today in pm offices in iran. summary comorbidity of headache and gi abnormalities has become a subject of interest to researchers in recent years. there is evidence supporting the association of various gi disorders with primary headaches classified by the ihs. in addition to functional gi diseases, ibd and cd along with h.pylori infection are also reported to be present in a substantial number of patients with headache. furthermore, there is a growing body of literature demonstrating improvement or resolution of headache following management of the accompanying gi disorder. this raises the idea of existence of a possible unique diagnostic entity in the classification of headache disorders, the “headache of gastrointestinal origin”. this was once believed by ancient scholars namely râzi and ebne-sina. they practiced treatment of this kind of headache in their patients and expressed their experiences in their writings. this entity may provide explanation for headaches which resolve following treatments targeting the associated gi disorder. efforts should be made to clarify this type of headache, however arriving at a strict criteria may be challenging. patients fulfilling criteria for any type of primary headaches through the ichd, should be thoroughly questioned about gi symptoms. if any gi abnormality, either functional or organic, is detected, especially outside the bouts of headaches, treatment targeting the gi abnormality is instituted. once the gi abnormality is managed, symptoms of the primary headache are reevaluated. if headaches are improved or completely resolved, the headache would be the one of gastrointestinal origin and the patient may be given the diagnosis of “headache attributed to gi disorders”. acknowledgments: the authors would like to thank dr. r choopani for his helpful suggestions. conflict of interest: the authors declare that they have no conflict of interest. funding support: none. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. spierings e. reflux-triggered migraine headache originating from the upper gum/teeth. cephalalgia. 2002;22(7):555-6. 2. spierings el. headache of gastrointestinal origin: case studies. headache. 2002;42(3):217-9. 3. fazljou smb, 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2002. http://www.traditionalmedicine.net.au/graecarb.htm http://www.traditionalmedicine.net.au/chapter2.htm emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 127 emergency (2016); 4 (3): 127-131 original research diagnostic value of clinical findings in evaluation of thoracolumbar blunt traumas ali shahrami1, majid shojaee1, seyed mohammadreza tabatabaee1*, elaheh mianehsaz2 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. clinical research support center, kashan university of medical sciences, kashan, iran. *corresponding author: seyed mohammadreza tabatabaei; emergency department, imam hossein hospital, shahid madani avenue, tehran, iran. tel: +989133619199 email: moh.tab35@yahoo.com received: july 2015; accepted: august 2015 abstract introduction: necessity of imaging for symptom-free conscious patients presented to emergency department (ed) following traumatic thoracolumbar spine injuries has been a matter of debate. the present study was aimed to evaluate the diagnostic value of clinical findings in prediction of traumatic thoracolumbar injuries compared tocomputed tomography (ct) scan. methods: the present diagnostic value study was carried out using non-random convenience sampling during the time between october 2013 and march 2014. all trauma patients > 15 years old underwent thoracolumbar ct scan were included. correlation between clinical and ct findings was measured using spss 21.0 and screening performance characteristics of clinical findings in prediction of thoracolumbar fracture were calculated. results: 169 patients with mean age of 37.8 ± 17.3 years (rage: 15-86) were evaluated (69.8% male). all fracture patients had at least 1 positive finding in history and physical examination. the fracture was confirmed in only 24.6% of the patients with positive findings in history or physical examination. in 37.5% of patients the location of fracture, matched the area of positive physical examinations. sensitivity, specificity, ppv, npv, plr, and nlr of clinical findings in comparison to thoracolumbar ct scan were 100 (95% ci: 89 100), 1.5 (95% ci: 0.2-6), 24.5 (95% ci: 18.3-31.9), 100 (95% ci: 19.7-100), 32.5 (95% ci: 24.6-43.03), and infinite, respectively. conclusion: the results of the present study, show the excellent screening performance characteristics of clinica l findings in prediction of traumatic thoracolumbar fracture (100% sensitivity). it could be concluded that in conscious patients with stable hemodynamic, who have no distracting pain and are not intoxicated, probability of thoracolumbar fracture is very low and near to zero in case of no positive clinical finding. keywords: spinal fractures; physical examination; tomography, x-ray computed; signs and symptoms cite this article as: shahrami a, shojaee m, tabatabaei sm, mianehsaz e. diagnostic value of clinical findings in evaluation of thoracolumbar blunt traumas. emergency. 2016; 4(3):127-131. introduction: ultiple trauma patients make up a considerable portion of emergency department (ed) visitors. spine is prone to injury following trauma. traumatic spinal injuries bring about various and sometimes dangerous outcomes such as spinal cord injury, neurologic injuries, chronic pain, deformity, transient or permanent functional disorders, and decreased quality of life (1-3). about 50% of spinal fractures occur in the thoracolumbar area and 19% to 50% of them lead to neurologic injuries (4, 5). incidence of traumatic spinal cord injuries has been reported to be 3.6 cases per million population in canada and 23 per million around the world. in iran, due to various reasons such as high rate of traffic accidents and not conducting occupational safety, the incidence has been much higher and estimated to be about 30 to 72.4 cases per million (6). misdiagnosis incidence has been reported to be up to 20% in thoracolumbar blunt traumas. late diagnosis of these injuries leads to 7-8 times increase in neurologic complications (4, 5, 7, 8). therefore, early diagnosis and triage of the patients in need of complimentary diagnostic and curative measures is of great importance in managing these patients. most researchers believe thoracolumbar trauma patients with pain, tenderness, positive neurologic findings, loss of consciousness, multiple trauma, and those unable to go through detailed physical examination should undergo imaging. (4, 9-11) necessity of imaging for symptom-free conscious patients has been a matter of debate (10, 12-19). using clinical decision m this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shahrami et al 128 rules such as national emergency x-radiography utilization study (nexus) and canadian c-spine rule can be helpful in this regard (20-22). despite the higher prevalence of thoracolumbar area injuries compared to cervical ones, less research has been done on trauma in this area and there is much controversy regarding its management (9, 23). although physical examination is highly important in diagnosis of thoracolumbar area injuries, its accuracy is a matter of question. based on a review study, physical examination can only predict 27-56% of thoracolumbar fractures in patients with blunt trauma and its sensitivity and specificity have been estimated to be 48.2% and 84.9%, respectively (4). based on the afore-mentioned points, the present study was aimed to evaluate the diagnostic value of clinical findings in prediction of thoracolumbar traumatic spinal injuries in comparison with computed tomography (ct) scan. methods: study design and setting the present diagnostic value study was carried out using non-random convenience sampling during the time between october 2013 and march 2014 in the ed of imam hossein hospital, tehran, iran. inclusion and exclusion criteria all patients over 15 years of age who were presented to the ed following multiple trauma and underwent thoracolumbar ct scan were included. patients with decreased level of consciousness, hemodynamic instability, distracting pain, intoxicated following alcohol, opiate or sedative drug use, and those who did not fully participate during physical examination for any reason were excluded. in the present study, positive clinical finding was considered the presence of any of the following items in history of physical examination: back pain, midline tenderness, lateral tenderness, skin abrasion or laceration, and focal neurologic deficit (sensory/motor). data gathering demographic data (age, sex), trauma mechanism (traffic accident, falling, assault, direct collision with a h object, rubble), history and physical examination findings (thoracolumbar pain, midline or lateral thoracolumbar table 1: baseline characteristics of the participants variables number of patients (%) without fracture with fracture age (years) < 20 21 (12.4) 3 (7.5) 20-30 55 (32.5) 13 (32.5) 30-40 30 (17.7) 5 (12.5) 40-50 23 (13.6) 8 (20) 50-60 19 (11.2) 6 (15) > 60 21 (12.4) 5 (12.5) fracture site thoracic 17 (10) 17 (42.5) lumbar 22 (13) 22 (55) thoracolumbar 1 (0.6) 1 (2.5) trauma mechanism collision 93 (55) 20 (50) falling down 49 (29) 14 (35) assault 7 (1.4) 1 (2.5) hard object collision 18 (10.7) 5 (12.5) rubble 2 (1.1) 0 (0) fracture type compression or wedge 15 (9) 15 (37.5) burst 6 (4) 6 (15) chance 1 (0.6) 1 (2.5) fracture-dislocation 2 (1.1) 2 (5) body and process 4 (2.3) 4 (10) transverse process 9 (5.3) 9 (22.5) spinous process 2 (1.1) 2 (5) facet or articular process 0 (0) 0 (0) pars inter-articular or listhesis 1 (0.6) 1 (2.5) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 129 emergency (2016); 4(3): 127-131 tenderness, bruises and laceration, step or gap touch, deformity, neurological sensorimotor disorder) and thoracolumbar ct scan findings regarding presence or absence of fracture(s) were gathered and recorded using a checklist. history was obtained and physical examination was performed by a third-year emergency medicine resident. all ct scans were interpreted by an independent radiologist blind to the clinical findings. this study did not interfere with the treatment process and imaging performance in the patients. statistical analyses spss version 21 was used for statistical analyses. the required sample size for this study was estimated to be 160 cases, based on 48.2% sensitivity of the clinical findings compared to ct scan in vertebra fracture (16), α = 0.1, z1-α/2 = 1.96, l = 0.1, and sn = 0.482. the results were reported as mean ± standard deviation (sd) for quantitative data and as frequency and percentage for qualitative ones. quantitative data were compared using t-test and mann-whitney test and qualitative ones were compared using chi-square and fisher’s exact tests. correlation between quantitative variables was measured using pearson correlation coefficient and spearman rank correlation. sensitivity, specificity, positive and negative predictive values (ppv and npv), and positive and negative likelihood ratios (plr and nlr) of clinical findings in prediction of thoracolumbar fracture were determined. thoracolumbar ct scan was considered as the standard reference test. p < 0.05 was defined as significance level. results: 169 patients with mean age of 37.8 ± 17.3 years (rage: 15-86) were evaluated (69.8% male). table 1 shows baseline characteristics of the studied patients. the most frequent fractures are second and third lumbar vertebrae fractures with 11 (27.5%) and 8 (20%) cases, respectively, and 12th thoracic vertebra with (20%). table 2 summarizes the findings of patients’ history and physical examination. all fracture patients had at least 1 positive finding in history and physical examination. the fracture was confirmed in only 24.6% of the patients with positive findings in physical examination or history. in 37.5% of patients the location of fracture, matched the area of positive physical examinations, while in 40% of the cases, the area affected with tenderness was bigger than the fractured vertebra. sensitivity, specificity, ppv, npv, plr, and nlr of clinical findings in comparison to thoracolumbar ct scan were 100 (95% ci: 89 100), 1.5 (95% ci: 0.2-6), 24.5 (95% ci: 18.3-31.9), 100 (95% ci: 19.7-100), 32.5 (95% ci: 24.6-43.03), and infinite, respectively. discussion: based on the results of this study, history and physical examination have 100% sensitivity and npv in screening thoracolumbar trauma patients. in fact, the probability of thoracolumbar fracture in conscious patients with stable hemodynamic, who have no positive finding in history and physical examination, is very low. in the present study, like previous ones, men were affected by trauma and thoracolumbar spinal fracture more than women, and the 20-30 years age range had the highest prevalence of fracture (4, 24-26). in this study, the most frequent trauma mechanism was traffic accidents, especially pedestrian-car accidents, which was in line with the results of yousefzadeh and inaba (17, 24). in contrast, studies by heidary (25), table 2: history and physical examination of the patients findings number of patients (%) without fracture with fracture back pain no 8 (4.7) 3 (1.8) yes 121 (71.6) 37 (21.9) midline tenderness no 101 (59.8) 10 (5.9) yes 28 (16.6) 30 (17.8) lateral tenderness no 90 (53.3) 19 (11.2) yes 39 (23.1) 21 (12.4) abrasion no 65 (38.5) 18 (10.7) yes 64 (37.9) 22 (13) neurologic examination normal 128 (75.7) 37 (21.9) abnormal 1 (0.6) 3 (1.8) movement not moving 2 (1.2) 3 (1.8) just lateral 4 (2.4) 5 (3) can sit 11 (6.5) 10 (5.9) can stand up 5 (3) 5 (3) can walk 107 (63.3) 17 (10.1) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com shahrami et al 130 rahimi-movaghar (27), and fakharian (26) in iran, and karamehmetoglu in turkey (28) reported falling as the most prevalent mechanism for thoracolumbar spinal trauma. in most studies, as well as the present one, the most common type of fracture was compression (4, 16). while, fakharian et al. showed that burst fracture was more common. they believed that the studied population being neurosurgery patients was the reason for this difference (26). in the present study, no difference was detected regarding clinical findings neither between men and women nor in various age ranges. back pain was the most common complaint in patients with or without spinal fracture. also in patients with spinal fracture, midline tenderness was the most common symptoms. the prevalence of positive neurologic findings in physical examination was 2.4%. in contrast, this rate was estimated to be 18% in yousefzadeh et al. study, 17% in the fakharian et al. study, and 20% in hsu jm et al. study (9, 24, 26). the reason for the low rate of positive neurologic findings in the present study can be excluding patients with distracting pain, decreased level of consciousness, and intoxicated; as logically the prevalence of neurologic disorders may be higher in this group due to more severe trauma. in a study by frankel et al. 60% and in the one by cooper et al. 31% of the patients with thoracolumbar fracture were symptom-free (29, 30). in our study, 15% of these patients had normal physical examinations. in 37.5% of patients with fracture, the area of positive physical examinations was completely in agreement with the true site of injury in ct scan, and in 40% of the patients, the area affected with tenderness was bigger than the fractured area in the ct scan. in the inaba et al. study, agreement rate between the site of pain and fracture was 61.6% (17). sensitivity of physical examination in predicting traumatic thoracolumbar spine injuries has been estimated to be about 48-85% in various studies (17, 31). the results of the present study show 100% sensitivity of history and physical examination in ruling out thoracolumbar fractures. samuel et al. also showed that normal history and physical examination are enough to rule out the probability of fracture (16). in short, clinical findings seem to be valuable in management of patients presented to the ed following traumatic thoracolumbar injuries. limitations and suggestions since patients with distracting injuries (patients with abdominal or chest problems or big bone fracture) were excluded, calculation of injury severity score had no value. it is suggested to carry out a more comprehensive study without excluding these patients and calculate sensitivity and specificity of various items of physical examination in all thoracolumbar trauma patients including conscious and unconscious ones, with and without distracting injuries. short and long term follow-up of the patients, which are routinely managed based on clinical findings and discharged without undergoing imaging study, can be very helpful in confirmation and external validation of this management approach. conclusion: the results of the present study, show the excellent screening performance characteristics of clinical findings in prediction of traumatic thoracolumbar fracture (100% sensitivity). it could be concluded that in conscious patients with stable hemodynamic, who have no distracting pain and are not intoxicated, probability of thoracolumbar fracture is very low and near to zero in case of no positive clinical finding. acknowledgments: we would like to thank all professors and staff of emergency department and radiology specialists at imam hossein hospital, tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. diaz jr jj, cullinane dc, altman dt, et al. practice management guidelines for the screening of thoracolumbar spine fracture. journal of trauma and acute care surgery. 2007;63(3):709-18. 2. wood 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cervical spine in patients with blunt trauma. new england journal of medicine. 2000;343(2):94-9. 22. stiell ig, wells ga, vandemheen kl, et al. the canadian cspine rule for radiography in alert and stable trauma patients. jama. 2001;286(15):1841-8. 23. holmes jf, panacek ea, miller pq, lapidis ad, mower wr. prospective evaluation of criteria for obtaining thoracolumbar radiographs in trauma patients. the journal of emergency medicine. 2003;24(1):1-7. 24. chabok sy, safaee m, alizadeh a, dafchahi ma, taghinnejadi o, koochakinejad l. epidemiology of traumatic spinal injury: a descriptive study. acta medica iranica. 2010;48(5):308-11. 25. pedram h, reza zm, reza rm, vaccaro ar, vafa r-m. spinal fractures resulting from traumatic injuries. chinese journal of traumatology (english edition). 2010;13(1):3-9. 26. fakharian e, masoud s, tabesh h. an epidemiologic study on spinal injuries in kashan. 2004. 27. rahimi-movaghar v, saadat s, jafarpour s. establishment of a regional multicenter traumatic spine fracture/dislocation registry. chinese journal of traumatology. 2014;17(4):235-8. 28. karamehmetoglu s, nas k, karacan i, et al. traumatic spinal cord injuries in southeast turkey: an epidemiological study. spinal cord. 1997;35(8):531-3. 29. frankel hl, rozycki gs, ochsner mg, harviel jd, champion hr. indications for obtaining surveillance thoracic and lumbar spine radiographs. journal of trauma and acute care surgery. 1994;37(4):673-6. 30. cooper c, dunham cm, rodriguez a. falls and major injuries are risk factors for thoracolumbar fractures: cognitive impairment and multiple injuries impede the detection of back pain and tenderness. journal of trauma and acute care surgery. 1995;38(5):692-6. 31. sava j, williams md, kennedy s, wang d. thoracolumbar fracture in blunt trauma: is clinical exam enough for awake patients? journal of trauma and acute care surgery. 2006;61(1):168-71. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 11 emergency (2016); 4 (1): 11-15 original research the accuracy of urinalysis in predicting intra-abdominal injury following blunt traumas anita sabzghabaei1, majid shojaee2, saeed safari3, hamid reza hatamabadi2, reza shirvani2* 1department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2 department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 3 department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: reza shirvani; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. postal code: 1989934148; tel/fax: 00982122721155 email: rshirvani.md@gmail.com received: february 2015; accepted: april 2015 abstract introduction: in cases of blunt abdominal traumas, predicting the possible intra-abdominal injuries is still a challenge for the physicians involved with these patients. therefore, this study was designed, to evaluate the accuracy of urinalysis in predicting intra-abdominal injuries. methods: patients aged 15 to 65 years with blunt abdominal trauma who were admitted to emergency departments were enrolled. abdominopelvic computed tomography (ct) scan with intravenous contrast and urinalysis were requested for all the included patients. demographic data, trauma mechanism, the results of urinalysis, and the results of abdominopelvic ct scan were gathered. finally, the correlation between the results of abdominopelvic ct scan, and urinalysis was determined. urinalysis was considered positive in case of at least one positive value in gross appearance, blood in dipstick, or red blood cell count. results: 325 patients with blunt abdominal trauma were admitted to the emergency departments (83% male with the mean age of 32.63±17.48 years). sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of urinalysis, were 77.9% (95% ci: 69.6-84.4), 58.5% (95% ci: 51.2-65.5), 56% (95% ci: 48.5-63.3), 79.6% (95% ci: 71.8-85.7), 1.27% (95% ci: 1.30-1.57), and 0.25% (95% ci: 0.18-0.36), respectively. conclusion: the diagnostic value of urinalysis in prediction of blunt traumatic intra-abdominal injuries is low and it seems that it should be considered as an adjuvant diagnostic tool, in conjunction with other sources such as clinical findings and imaging. key words: urinalysis; abdominal injuries; abdomen; tomography, x-ray computed cite this article as: sabzghabaei a, shojaee m, safari s, hatamabadi hr, shirvani r. the accuracy of urinalysis in predicting intraabdominal injury following blunt traumas. emergency. 2016;4(1):11-15. introduction: bdominal trauma is the most common cause of mortality in people under 45 years old. in cases of blunt trauma, evaluating and diagnosing the possible intra-abdominal injuries is still a challenge for the physicians involved with these patients (1). frequent clinical examinations, aspiration and diagnostic peritoneal lavage, ultrasonography, computed tomography (ct), biochemical and urine tests are among the most common diagnostic tools in this regard (2). in trauma patients, physical examination of the abdomen might not give accurate information on the state of intra-abdominal injuries. this problem is even worse in patients with a decreased level of consciousness as a result of using alcohol, drugs, brain trauma, and hemodynamic instability (3-5). abdominal ct scan with intravenous (iv) contrast media is considered a standard diagnostic imaging and has the ability to diagnose solid organ injuries, accurately (1). yet, this method cannot be used on patients with emergency exploratory laparotomy indication, restlessness, a history of allergy to contrast material, and hemodynamic instability(6, 7). urinalysis accompanied by frequent physical examination has been proposed as an initial method for evaluating those affected by blunt abdominal trauma, especially children (8-10). some of the studies believe that patients with normal urinalysis and abdominal physical examination rarely have intra-abdominal injuries (8, 11, 12). in contrast, another study expressed that the presence or absence of blood in urine is not an accurate and safe tool to predict the existence of intra-abdominal injuries (13). also other studies have shown that biochemical tests, a this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com sabzghabaei et al 12 evaluating urobilinogen and urine bilirubin accompanied by urinalysis, cannot be an effective tool for abdominal trauma screening in children (14-16). meaning, despite urinalysis being a valuable diagnostic tool, it might not be efficient in cases of traumatic abdominal injuries (17, 18). therefore, performing urinalysis when clinical examination and ultrasonography results are normal and the patient does not show any hemodynamic instability or decrease in consciousness, wastes lots of time and resources in the overcrowded trauma centers. in addition, at times the positive urinalysis leads to unnecessary further diagnostic tests. this study was aimed to assess the accuracy of urinalysis in predicting intraabdominal injuries following blunt traumas. methods: this diagnostic accuracy assessment study evaluated urinalysis in predicting traumatic intra-abdominal injuries. abdominopelvic ct scan with iv contrast was considered as gold standard test. patients aged 15 to 65 years with blunt abdominal trauma who were admitted to emergency departments of imam hossein and shohadaye haftome tir hospitals, tehran, iran between march and september 2013, were enrolled. women on their menstrual cycle, people with underlying diseases such as cancer or chronic kidney diseases, and people with penetrating abdominal trauma were excluded. urinalysis and abdominopelvic ct scan with iv contrast were performed for all patients, simultaneously. demographic data, trauma mechanism (motor vehicle accidents, pedestrian motor crash, or falling), the results of urinalysis (gross appearance, presence or absence of blood in the dipstick, and red blood cell count), and the results of abdominopelvic ct scan were gathered using a pre-designed checklist. all patients were examined with a multi-slice ct scanner (siemens medical solution, usa). a radiologist who was blind to the results of urinalysis and clinical characteristics did interpretation of the patients’ ct scan. in addition, a laboratory technician who was blind to the patients’ clinical data did urinalysis. in the end, the relationship between the results of abdominopelvic ct scan, and urinalysis was assessed. the ethics committee of shahid beheshti university of medical sciences approved this study. in addition, the researchers adhered to the principles of helsinki declaration and confidentiality of patient information over the course of the research. written informed consents were obtained from all patients. in this study, clear gross appearance of urine was defined as the ability to read a text through the urine-containing glass. in addition, semi-clear urine was defined as urine being a little turbid while a text can still be read through the glass. semi-turbid and turbid urines were also defined as urines being a little to completely cloudy so that the text could not be read through the glass containing them. urinalysis was considered positive in case of at least one positive value in gross appearance, blood in dipstick, or red blood cell count. red blood cell counts were categorized to 0-9, 10-40, and more than 40. considering 59% sensitivity, 10% specificity and a confidence interval of 95%, the minimum sample size was calculated 93 patients. data were analyzed using spss version 21.0. screening performance characteristics of urinalysis (sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), positive likelihood ratio (plr), and negative likelihood ratio (nlr)) with 95% confidence interval (95% ci) in comparison with the results of abdominopelvic ct scan were calculated. p<0.05 was considered as the level of significance. results: finally, 325 patients with blunt abdominal trauma with the mean age of 32.63±17.48 years were evaluated (83% male). trauma mechanism in 36% was motor vehicle collision. most patients had clear urine appearance (59.1%), blood negative dipstick (48%), with 0-9 red blood cells per high power field (58.8%). the results from the patients’ urinalysis can be found in table 1. 193 (59.6%) patients had normal abdominopelvic ct scan while pelvic fracture were detected in 58 (18%), free abdominal fluid in 37 (11%), kidney damage in 32 (10%), liver damage in 23 (7%), spinal fracture in 22 (7%), and spleen damage in 18 (6%). there was a significant but weak correlation between the gross appearance of urine (r=0.28, p˂0.001), the results of urine dipstick (r=0.42, p˂0.001), and red blood cell count (r=0.37, p˂0.001) and the results of abdominopelvic ct scan. table 1: the results of urinalysis regarding gross appearance, blood in dipstick, and red blood cell count urinalysis number (%) gross appearance clear 192 (59/1) semi clear 77 (23/7) semi turbid 29 (8/9) turbid 27 (8/3) blood in dipstick 0 156 (48) 1 42 (12/9) 2 53 (16/3) 3 40 (12/3) 4 34 (10/5) red blood cell count 0-9 cells/hpf* 191 (58/8) 10-40 cells/hpf 83 (24/3) 40< cells/hpf 51 (16/9) this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 13 emergency (2016); 4 (1): 11-15 sensitivity, specificity, ppv, npv, plr, and nlr of urinalysis were 77.9% (95% ci: 69.6-84.4), 58.5% (95% ci: 51.2-65.5), 56% (95% ci: 48.5-63.3), 79.6% (95% ci: 71.8-85.7), 1.27% (95% ci: 1.30-1.57), and 0.25% (95% ci: 0.18-0.36), respectively. in addition, screening performance characteristics of gross appearance, dipstick and red blood cell count in predicting the possibility of intra-abdominal solid organ injuries including liver, spleen, kidney and also presence or absence of abdominal free fluid are shown in tables 2, 3, and 4, respectively. discussion: the results of this study show that sensitivity and specificity of urinalysis in predicting intra-abdominal injuries is low. it seems that using urinalysis for predicting traumatic abdominal injuries is not accurate enough. rapid diagnosis and timely treatment of abdominal traumas is very important and can play an important role in decreasing mortality rates among patients (19-21). different studies express various, and sometimes contradicting, opinions on the accuracy of urinalysis in blunt abdominal trauma. in a study, wessel et al. introduced ultrasonography and urinalysis as the optimal tools for an initial evaluation to exclude renal injury following blunt abdominal trauma (22). in addition, isaacman et al. demonstrated that the prevalence of laboratory abnormalities was low in pediatric trauma patients and recommended a combination of physical examination and urinalysis as a highly sensitive screening tool. they showed that laboratory testing in patients with a normal physical examination and urinalysis rarely identified missed intra-abdominal injury (8). caparo et al. studied the trauma panels’ tests such as sodium, glucose, white blood cell (wbc) count, hematocrit, platelets, prothrombin time, activated partial thromboplastin time, aspartate aminotransferase (ast), alanine aminotransferase (alt), amylase, lipase, and urinalysis in pediatric patients with blunt trauma. their results showed that abnormal values for glucose, ast, urinalysis, and wbc count were the most commonly observed. they concluded that routine trauma panels could not be used as a table 2: screening performance characteristics of urine gross appearance in comparison with the results of abdominopelvic computed tomography scan characteristics kidney spleen liver free fluid sensitivity 60.6 (42.2-76.1) 66.7 (41.1-85.6) 39 (20.4-61.2) 59.4 (42.2-74.8) specificity 61.3 (55.4-66.8) 60.5 (54.8-66) 50 (44.6-55.3) 61.4 (55.5-67) ppv1 15.0 (9.0-22.5) 9.0 (4.9-15.5) 42.8 (22.3-65.5) 16.5 (10.8-24.2) npv2 93.2 (88.4-96.1) 96.8 (93-98.7) 92.7 (87.8-95.8) 92.2 (87.2-95.4) plr3 0.17 (0.11-0.26) 0.09 (0.05-0.2) 0.75 (0.40-1.3) 0.19 (0.1-0.3) nlr4 0.07(0.04-0.12) 0.03 (0.01-0.07) 0.07 (0.04-0.1) 0.08 (0.05-0.1) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. table 3: screening performance characteristics of urine blood in comparison with the results of abdominopelvic computed tomography scan characteristics kidney spleen liver free fluid sensitivity 15.9 (10.9-22.5) 8.2 (4.7-13.7) 8.8 (5.2-14.4) 16.5 (11.4-23.2) specificity 96.1 (91.4-98.4) 97.4 (93.1-99.1) 94.8 (89.8-97.5) 94.2 (89.0-97.1) ppv1 81.8 (63.9-92.3) 77.7 (51.9-92.6) 65.2 (42.8-82.8) 75 (58.4-87.6) npv2 51.3 (45.4-57.2) 49.5 (43.7-55.2) 49 (43.2-54) 51 (45.1-56.9) plr3 4.5 (2.1-9.4) 3.5 (1.42-8.59) 1.87 (0.99-3.5) 3.1 (1.7-5.6) nlr4 0.94 (0.8-1.1) 1.01 (0.9-1.1) 1.04 (0.9-1.2) 0.95 (0.8-1.1) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. table 4: screening performance characteristics of urine red blood cell count in comparison with the results of abdominopelvic computed tomography scan characteristics kidney spleen liver free fluid sensitivity 18.1(9.5-31.3) 10.9 (4.5-22.9) 9.0 (3.3-20.7) 16.3 (8.2-29.3) specificity 91.4 (87.3-94.4) 95.5 (92.1-97.5) 93.3 (89.4-95.8) 99.1 (96.7-99.8) ppv1 30.3 (16.2-48.8) 33.3 (14.3-58.8) 21.7 (8.2-44.2) 81.8 (47.7-96.7) npv2 84.5 (79.8-88.4) 84.0 (79.3-87.8) 83.4 (78.6-87.3) 84 (79.1-87.9) plr3 0.43 (0.2-0.8) 0.5 (0.24-1.03) 0.27 (0.12-0.62) 4.5 (1.24-16.2) nlr4 0.18 (0.13-0.23) 0.18 (0.14-0.24) 0.19 (0.15-0.25) 0.19 (0.14-0.24) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com sabzghabaei et al 14 screening tool in children with blunt trauma (14). in a study by stein et al. the degree of hematuria did not correlate with the degree of renal injury. based on their findings, any child with a history of blunt abdominal trauma and any evidence of hematuria should undergo abdominopelvic ct scan for correct diagnosis (23). kennedy et al. showed that urinary dipstick is a safe, accurate, and reliable screening test for evaluating the presence or absence of hematuria in patients suffering from either blunt or penetrating abdominal trauma (24). perez-brayfield et al. declared that abdominopelvic ct scan should only be done when the patient’s urinalysis shows an red blood cell count of 50 or more (25). yet, in a study by keller et al. routine laboratory tests such as urinalysis had little value in the management of injured children (16). in other studies, although urinalysis was valuable in specific patient populations, it showed moderate bias in predicting abdominal injury in traumatic children and was not helpful(17, 18). we can conclude that practically it is not possible to distinguish the patients with intraabdominal injuries from the others solely using urinalysis. this study was carried out in centers, which perform urinalysis for most of the patients with possible abdominal trauma, but only the patients that are thought to have a higher possibility of abdominal trauma are scanned. therefore, maybe the results of this study cannot be generalized. to be able to generalize the results of this study a broader study in multiple centers is recommended. conclusion: the diagnostic value of urinalysis in prediction of blunt traumatic intra-abdominal injuries is low and it seems that it should be considered as an adjuvant diagnostic tool in conjunction with other sources such as clinical findings and imaging. acknowledgments: this article has been extracted from dr. reza shirvani’s thesis for achieving his specialist degree in emergency medicine from the faculty of medicine at shahid beheshti university of medical sciences. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria 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trauma mechanism is not valuable to detect urogenital injury. emerg med j. 2013:emermed-2013-202651. 18. thorp aw, young tp, brown l. test characteristics of urinalysis to predict urologic injury in children. west j emerg med. 2011;12(2):168. 19. shojaee m, faridaalaee g, yousefifard m, et al. new scoring system for intra-abdominal injury diagnosis after blunt trauma. chin j traumatol. 2014;17(1):19-24. 20. shojaee m, faridaalaee g, sabzghabaei a, et al. sonographic detection of abdominal free fluid: emergency residents vs radiology residents. trauma mon. 2013;17(4):377. this open-access article distributed under the terms of the creative commons attribution non commercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 15 emergency (2016); 4 (1): 11-15 21. alavi-moghaddam m, safari s, najafi i, hosseini m. accuracy of urine dipstick in the detection of patients at risk for crushinduced rhabdomyolysis and acute kidney injury. eur j emerg med. 2012;19(5):329-32. 22. wessel l, scholz s, jester i, et al. management of kidney injuries in children with blunt abdominal trauma. j pediatr surg. 2000;35(9):1326-30. 23. stein jp, freeman ja, kaji dm, esrig d, eastham j, ehardy b. blunt renal trauma 1n the pediatricpopulation: indications for radiographic evaluation. urology. 1994;44(3):406-10. 24. kennedy tj, mcconnell jd, thal er. urine dipstick vs. microscopic urinalysis in the evaluation of abdominal trauma. journal of trauma and acute care surgery. 1988;28(5):615-7. 25. perez-brayfield mr, gatti jm, smith ea, et al. blunt traumatic hematuria in children. is a simplified algorithm justified? j urol. 2002;167(6):2543-6. archives of academic emergency medicine. 2023; 11(1): e58 rev i ew art i c l e intra-operative adjunctive magnesium sulfate in pain management of total knee arthroplasty; a systematic review and meta-analysis amirali azimi1, fatemeh-sadat tabatabaei1∗, amirfarbod azimi1, hamid mazloom2, mohammad mehdi foruzanfar2, nastaran sadat mahdavi3 1. department of medicine, tehran university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of pediatric anesthesiology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. received: june 2023; accepted: july 2023; published online: 21 august 2023 abstract: introduction: there has been growing interest in the potential role of adjunctive magnesium sulfate in improving pain management. this systematic review and meta-analysis aimed to assess the effect of intra-operative adjunctive magnesium sulfate on pain management and opioid consumption in total knee arthroplasty (tka). methods: a comprehensive search was conducted in medline, embase, scopus, web of science, and cochrane library databases, covering studies up to april 2023. the extracted data included pain management outcomes, opioid consumption, and adverse effects from the selected studies. standardized mean differences (smds) were calculated for continuous outcomes, while risk ratios (rrs) were calculated for dichotomous outcomes. meta-analysis was conducted employing random-effects models in stata 17. results: in this meta-analysis of 8 randomized controlled trials involving 536 patients, adjunctive magnesium sulfate in tka was found to significantly reduce opioid consumption during the first 24 hours after operation (smd: -1.88, 95% confidence interval (ci): [-3.66 to -0.10]; p = 0.038). it also resulted in lower pain scores at rest 24 hours after surgery (smd: -1.53, 95% ci: [-2.70 to -0.37]; p = 0.010). there were no significant differences in time to first rescue analgesic and adverse effects between the groups. the included studies were assessed to have low to high levels of risk of bias. conclusion: this study presents evidence at low to moderate levels supporting the use of intra-operative adjunctive magnesium sulfate in tka for improved pain management and reduced opioid consumption. however, further research is needed to address the heterogeneity and to explore optimal dosing regimens and routes of administration to maximize the benefits of magnesium sulfate in tka. keywords: arthroplasty, replacement, knee; magnesium sulfate; pain management; analgesics, opioid; meta-analysis cite this article as: azimi a, tabatabaei f, azimi a, mazloom h, foruzanfar mm, mahdavi ns. intra-operative adjunctive magnesium sulfate in pain management of total knee arthroplasty; a systematic review and meta-analysis. arch acad emerg med. 2023; 11(1): e58. https://doi.org/10.22037/aaem.v11i1.2058. 1. introduction total knee arthroplasty (tka) is a common surgical procedure that relieves pain and improves function in patients with end-stage knee osteoarthritis (1). however, effective postoperative pain management remains a challenge, and the excessive use of opioids is often associated with adverse effects, delayed recovery, and increased healthcare costs (2). ∗corresponding author: fatemeh-sadat tabatabaei; department of medicine, tehran university of medical sciences, poursina st., 16 azar st., keshavarz blvd., tehran, iran. phone: 00989120364374, email: fatimast1995@gmail.com, fs-tabatabaei@alumnus.tums.ac.ir, orcid: https://orcid.org/0000-0003-2975-3543. therefore, there is a growing interest in identifying adjunctive therapies that can enhance pain control and reduce opioid requirements following tka (3-5). magnesium sulfate, a well-known mineral supplement, has attracted attention for its potential analgesic properties and opioid-sparing effects (6). magnesium, an essential cofactor in numerous enzymatic reactions, is involved in the modulation of n-methyl-d-aspartate (nmda) receptors, calcium channels, and inflammatory mediators (7, 8). by modulating these pathways, magnesium sulfate has been hypothesized to possess analgesic properties, reduce central sensitization, and decrease the need for opioid analgesics (9-11). studies examining the administration of magnesium have reported varying outcomes depending on the route of adminthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 2 istration. intravenous (iv ) administration of magnesium has been extensively studied and has shown consistent reductions in pain and opioid consumption in various surgical procedures (12, 13). in contrast, the evidence regarding other routes, such as intrathecal injection, periarticular injection, and nerve blocks, is more limited and inconclusive (14-17). the potential analgesic benefits of intra-operative administration of magnesium sulfate have been investigated in several studies across various surgical procedures. a systematic review conducted in 2018 explored the use of intravenous magnesium sulfate specifically in orthopedic surgery and reported a reduction in postoperative analgesic consumption (18). similarly, a recent systematic review and meta-analysis examining the effect of intravenous magnesium in noncardiac surgery indicated that magnesium may reduce morphine consumption within the first day after the operation and prolong the time to the first analgesia (12). another systematic review and meta-analysis focused specifically on knee arthroscopic surgeries and found that adding magnesium sulfate to bupivacaine significantly improved analgesic efficacy (19). however, the specific impact of magnesium sulfate on pain and opioid consumption following tka has not been comprehensively evaluated. recent clinical trials investigating the effect of adjuvant magnesium on postoperative pain and opioid consumption following total knee arthroplasty have yielded conflicting findings (20-23). in this systematic review and meta-analysis, we aim to evaluate the effect of intra-operative administration of magnesium sulfate on postoperative pain, opioid consumption, time to first analgesic in patients undergoing tka, and its related adverse effects. secondary outcomes, including knee range of motion, patient satisfaction, and length of hospital stay, will also be assessed. by synthesizing the available evidence, we seek to convey an extensive review of the potential benefits of magnesium sulfate as an adjunctive therapy in tka. 2. methods the present study adhered to the guidelines outlined in the preferred reporting items for systematic reviews and metaanalyses (prisma) (24), ensuring that the systematic review and meta-analysis were conducted and reported in a rigorous and transparent manner. the study protocol was not registered by the authors prior to its commencement. the prisma checklist 2020 can be find in supplementary table 3 and 4. 2.1. study design the objective of this review was to evaluate the efficacy of intra-operative magnesium sulfate administration as part of routine analgesic management protocols in tka. the authors framed their study using the pico framework as follows: population (p): individuals of any gender and age who underwent tka. intervention (i): treatment with magnesium sulfate via intravenous, intrathecal, or regional routes, excluding oral administration. comparison (c): patients receiving the same medication as the magnesium group, but without magnesium addition. outcome (o): postoperative pain, opioid consumption, and adverse effects. 2.2. search strategy to identify relevant keywords related to tka and magnesium sulfate, a comprehensive approach was employed, including expert recommendations, mesh and emtree databases, as well as screening of titles, abstracts, and subject indexing of relevant articles. distinct search queries were formulated with relevant tags assigned to each specific database, including medline (via pubmed), embase, scopus, web of science, and cochrane library. searches were performed from the launch of the databases up until january 2023. the supplementary file provides an inclusive search strategy employed for each individual database utilized in this study. additionally, a search was conducted on clinicaltrials.gov and google scholar to identify any potentially relevant studies and review grey literature. furthermore, a manual search of the bibliographies of all selected articles during the full-text review was performed, along with forward and backward citation tracking, to identify additional relevant articles. the search was updated in april 2023, leading to the identification of one additional article (22), which was subsequently included in the final analysis. 2.3. eligibility criteria this study included randomized clinical trials (rcts) and prospective or retrospective observational studies that assessed the impact of intra-operative magnesium sulfate administration on the management of tka. there were no restrictions on language or publication date. the following routes of magnesium administration were considered: intravenous (iv ), epidural, intra-articular injection, peri-articular injection (pai), adductor canal block (acb), and femoral nerve block (fnb). studies evaluating oral magnesium supplementation or comparing magnesium in combination with another drug in the control group were excluded. additionally, studies that did not evaluate the main outcomes of interest or compared magnesium to other experimental interventions (instead of a control group) were also excluded. case-control studies, animal studies, duplicate reports, letters, case reports, case series, and reviews were also excluded. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e58 2.4. study selection the initial records retrieved from the search results were exported to endnote software version 20.0 to remove duplicate records. two independent authors (aa and ft) conducted a review of titles and abstracts to screen the articles. subsequently, the full texts of potentially eligible studies were obtained, and final studies were selected based on the predefined eligibility criteria. any disagreements were resolved through discussion. 2.5. outcomes of interest and definitions the primary outcomes of interest in this study were postoperative pain, opioid consumption, and adverse effects during the first two weeks post operation (po). postoperative pain refers to the intensity of pain experienced by patients. opioid consumption refers to the amount of opioid analgesics consumed by patients. the term "time to first analgesic" refers to the duration between the completion of the surgery and the moment when the patient requests the first rescue analgesic for pain relief. adverse effects encompass any undesired or negative effects resulting from the intra-operative administration of magnesium sulfate, including nausea, vomiting, hypotension, arrhythmias, respiratory depression, renal dysfunction, and allergic reactions. the secondary outcomes of interest included knee range of motion, patient satisfaction, and length of hospital stay. 2.6. data extraction the data entry process was carried out by two independent authors (aa and ft) using a pre-designed excel form. studies that provided data from a single registry were identified by reviewing the registry title, year, setting, and sample characteristics. in cases where data for meeting the study objectives were missing, we reached out to the corresponding authors of the articles and requested the necessary information or original data. for articles that presented data in the form of figures, plotdigitizer online software was utilized. data extraction involved gathering study characteristics (authors, location, methodology, and anesthesia strategy), patient demographics (population size, age, and gender), intervention details (route, and dosage), and control information (route, and medications used). the recorded outcomes included opioid consumption measured in oral morphine equivalents (ome), postoperative pain assessed using visual analog scale (vas) or numeric rating scale (nrs), adverse effects documented by frequency or numbers, length of hospital stay measured in days or hours, and knee range of motion (rom) reported in degrees. the "time to first analgesic" data was collected and recorded in minutes or hours following the surgery. the conversion equivalents employed in this review were as follows: 1 mg of morphine (iv/im/sc) was considered equivalent to 0.01 mg of fentanyl (iv or epidural) and 10 mg of pethidine (iv/im). these conversion factors were utilized to standardize and compare opioid dosages across different administration routes based on the recommendations of uptodate (25). in staged tka studies, data pertaining to the first knee operated was collected and analyzed. 2.7. risk of bias assessment due to the limited number of observational studies included, the meta-analysis in this study focused solely on rcts. to assess the quality of these studies, the second version of the cochrane risk of bias assessment tool was employed (26). two independent authors (aa and ft) evaluated all included articles using the criteria outlined in this tool and made decisions based on the available data. the assessment of bias in the included studies was conducted based on several domains, including randomization, deviations from intended interventions, missing data, outcome measurement, and selection of reported outcomes. a classification of "low" was assigned to studies with no risk of bias in any of these domains. on the other hand, if "some concerns" or "high" were identified in more than one domain, the overall rating was categorized as "some concerns" or "high" accordingly. 2.8. certainty of evidence the authors employed the grading of recommendations, assessment, development, and evaluations (grade) guideline to determine the level of evidence for each outcome (27). publication bias, risk of bias assessments, inconsistency, imprecision, and indirectness, were taken into consideration. based on these assessments, the level of evidence for each investigated outcome was reported as high, moderate, low, or very low. 2.9. data synthesis and analysis the analysis of data was conducted using stata software (version 17) for the meta-analysis. the outcomes of postoperative pain and opioid consumption were assessed using the standardized mean difference (smd), while the analysis of adverse effects was performed using the risk ratio (rr). forest plots were employed to visually present the effect sizes of the evaluated outcomes. the subgroup analyses in this study were determined based on the specific follow-up time at which the desired outcome was evaluated. however, due to the limited number of included articles, subgroup analyses based on the route of magnesium administration could not be conducted. considering the variations in outcome measurement and intervention procedures across the included reports, it was expected that high heterogeneity would be present. to address this potential issue, random effects model was employed. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 4 heterogeneity among the results was assessed using the i2 statistic, following the classification by higgins (28). additionally, the egger’s test (29) was performed to examine the presence of publication bias. visual inspection of the funnel plot by subgroup was also conducted to further evaluate publication bias and assess the symmetry of the data distribution. 3. results 3.1. search results the initial database search yielded a total of 401 articles based on the specified search strategy. an additional 4 studies were identified from the references of included papers. after removing duplicate records using endnote, the titles and abstracts of the remaining 195 studies were screened. from this screening, 20 specific studies were selected for a full-text review. following a thorough evaluation based on the eligibility criteria, 11 studies were excluded for various reasons (30-40), as depicted in figure 1. ultimately, 9 articles were deemed suitable for inclusion in the current investigation (20-23, 41-45). however only the 8 rcts were included in the meta-analysis. the process of study selection, as illustrated in the prisma flow diagram, can be found in figure 1. 3.2. study characteristics table 1 presents the baseline characteristics of the studies included in this review. the data used for the meta-analysis were derived from 8 rcts comprising a total of 536 patients. among these studies, 267 patients were allocated to the treatment group, and 269 patients to the control group. the other article had a retrospective observational methodology and was not involved in the meta-analysis. regarding the administration route of magnesium, two studies utilized intravenous administration (23, 41), two studies employed periarticular injection (21, 22), two studies utilized adductor canal block (20, 45), one study used femoral nerve block (43), and one study utilized the epidural catheter (44). due to the limited number of studies available, it was not possible to conduct subgroup analyses based on the route of magnesium administration. in the studies where magnesium was administered intravenously, the control group received normal saline as the control (23, 41, 42). however, in the other studies, the control group received local anesthetics, and in the intervention group, magnesium was prescribed in addition to these medications (20-22, 43-45). 3.3. main outcomes the results of the meta-analysis comparing opioid consumption in subgroups with different timing are presented in figure 2. the standardized mean difference of opioid consumption was not statistically significant in the first six hours (smd: -1.36, 95% confidence interval (ci): [-3.72 to 1.00]; pvalue = 0.260), 24 to 48 hours after operation (smd: -0.61, 95% ci: [-1.32 to 0.10]; p-value = 0.095), and 0 to 48 hours po (smd: -0.80, 95% ci: [-1.60 to 0.00]; p-value = 0.050). however, a statistically significant smd in favor of magnesium was observed in the 0 to 24 hours postoperative period (smd: -1.88, 95% ci: [-3.66 to -0.10]; p-value = 0.038). the forest plot in figure 3 illustrates the differences in pain among five subgroups. the pooled analysis revealed a significant decrease in pain for the intervention group 24 hours after the operation (smd: -1.53, 95% ci: [-2.70 to -0.37]; pvalue = 0.010). although the magnesium group showed favorable differences in pain compared to the control group in six hours, 12 hours, 48 hours, and 72 hours after the operation, these values were not statistically significant (all pvalues > 0.05). figure 4 displays a forest plot depicting the difference in time to first rescue analgesic based on a pooled analysis. the results indicate that the magnesium group did not significantly differ in time to first analgesic compared to the control group (smd: 6.72, 95% ci: [5.72 to 19.15]; p-value = 0.290). figure 5 illustrates the meta-analysis results for the adverse effects reported in the studies. the risk ratio analysis did not show a statistically significant increase in nausea (smd: -0.14, 95% ci: [-0.34 to 0.05], p-value = 0.156) or pruritus (smd: 0.26, 95% ci: [-0.40 to 0.91]; p-value = 0.446). 3.4. secondary outcomes in relation to the secondary outcomes of interest in this review, range of motion (rom) was assessed in only one study (22), which showed insignificant differences amid the intervention and control groups. two studies evaluated the length of hospital stay and found that magnesium had no advantage (20, 22). patient satisfaction with pain control was investigated in three studies (20, 23, 45), revealing no significant superiority in favor of the intervention group. summary of these outcomes can be found in supplementary table s1. 3.5. heterogeneity heterogeneity levels for all analyzed outcomes in each subgroup were reported in figures 2-5. high levels of heterogeneity were observed for opioid consumption (over 86% in all subgroups), pain (ranging from i2=0% to i2=98%), and time to first analgesic (i2=99%). however, the results indicated relatively low heterogeneity among the studies for the adverse effects (i2=0%). 3.6. publication bias the egger’s test was performed to assess small-study effects. the regression-based egger’s test showed a significant association between the effect size and the standard error for opithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e58 oid consumption (z = -6.25, p-value < 0.001), postoperative pain (z = -4.14, p-value < 0.001), and time to first rescue analgesic (z = 8.37, p-value < 0.001) suggesting the presence of small-study effects. funnel plots for opioid consumption, postoperative pain, and time to first analgesic are presented in supplementary figures s1, s2, and s3, respectively. overall, the funnel plots exhibited a symmetrical distribution of studies in each subgroup, suggesting little evidence of publication bias. 3.7. risk of bias figure 6 summarizes the assessment of the risk of bias for individual articles via the revised cochrane collaboration tool (rob 2). among the included studies, three were determined to have a low risk of bias, four were assessed as having a high risk of bias, and one study was deemed to have some concerns based on the authors’ judgment. despite variations in the risk of bias scores, all studies within each subgroup were included in the analysis due to the limited number of available studies. 3.8. certainty of the evidence the certainty of the evidence for each outcome in this study has been evaluated and reported based on the authors’ judgment using the grade approach. according to the assessment, the evidence for opioid consumption and postoperative pain was determined to be of low certainty. there was moderately certain evidence supporting the findings related to the time to first analgesic and adverse effects. supplementary table s2 contains additional information on the certainty of evidence for each outcome. 4. discussion this study was a systematic review and meta-analysis of the randomized clinical trials focusing on the effect of intraoperative magnesium sulfate in total knee arthroplasty. the results showed significant improvements in pain management with the use of adjunctive magnesium sulfate in tka. the key outcomes included reduced opioid consumption in the first 24 hours after operation and decreased postoperative pain 24 hours after operation. however, the effect size of magnesium sulfate varied among the different studies included in this analysis. there were no significant differences in time to first rescue analgesic and the incidences of postoperative nausea and pruritus. the use of magnesium in pain management has emerged as a state-of-the-art topic across various medical conditions. despite its recent surge in attention, a substantial number of studies have already been undertaken to explore its effectiveness. a recent systematic review conducted in 2021 examined the use of magnesium in various conditions, including post-operative pain, migraine, renal pain, chronic/neuropathic pain, and fibromyalgia. the review found a total of 50 randomized controlled trials specifically focusing on the post-operative setting (46). they concluded that although several studies have demonstrated the painrelieving and opioid-sparing effects of magnesium, it is important to note that not all studies have reported significant effects (47-50). studies investigating the effect of magnesium on pain mechanisms have highlighted the potential influence of the route of administration. specifically, some articles concentrated on a specific route of magnesium administration in the postoperative setting. for instance, a comprehensive metaanalysis conducted in 2020, encompassing 51 rcts, examined the impact of iv magnesium on postoperative usage in noncardiac operation. the findings indicated that intravenous magnesium, when used as part of a multimodal analgesia approach, may lead to a reduction in morphine consumption within the first 24 hours after surgery and postpone the first rescue analgesia following a noncardiac operation (12). in addition, another meta-analysis on 12 rcts evaluated the application of intrathecal magnesium as an analgesic addition for spinal anesthesia. the results indicated that the inclusion of intrathecal magnesium in the spinal anesthetic regimen led to a prolongation of opiate analgesia duration (17). another review of 21 studies on the use of magnesium sulfate in peripheral nerve blocks found that it effectively reduced pain scores 6 and 12 hours after surgery, and decreased postoperative analgesic use within the initial 24 hours after surgery (15). furthermore, it is important to consider that the nature of surgeries can vary, and orthopedic surgeries have been a specific focus in some studies. for instance, a systematic review comprising 11 rcts examined the efficacy of iv magnesium sulfate for postoperative pain control in the orthopedic setting (18). the review concluded that perioperative iv use of magnesium sulfate in orthopedic procedures may lead to a reduction in analgesic usage and mitigate adverse effects. these studies, however, failed to deliver solid proof of favorable effects on the postoperative level of pain or time to first narcotic need (18). additionally, another systematic review and meta-analysis involving six rcts evaluated the impact of combining magnesium with bupivacaine for arthroscopy (51). the findings revealed that the addition of magnesium was associated with a significantly prolonged duration of analgesia, delayed time to analgesic administration, reduced pain scores, and decreased analgesic usage (51). a metaanalysis on intra-articular magnesium for pain management following arthroscopic knee procedures showed that patients who received magnesium experienced lower pain scores at rest and with movement two, four, twelve, and 24h after surgery, and had reduced opioid consumption and longer this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 6 time to the first analgesic requirement (16). to our knowledge, the present study is the first to specifically evaluate the effect of intra-operative magnesium sulfate administration on total knee replacement. the results of this study demonstrated that magnesium sulfate administered via various routes, including intravenous, periarticular infiltration, adductor canal block, femoral nerve block, and intrathecal, reduced postoperative pain at rest 24 hours after surgery and opioid consumption within the first 24 hours postoperatively, which is consistent with previous studies (15-17, 46, 51). however, the findings of this study indicated that magnesium administration does not change the time to the first request for analgesics by the patients, which is in contrast with previous studies (16, 51). one possible reason for this controversy is the limited number of included studies in the meta-analysis of time to rescue analgesic in the current study. also, the effect size of time to first rescue analgesic had a great variation among the included studies ranging from smd of -0.02 to 26.53, which resulted in the high heterogeneity observed in the results. among the findings, the most clinically significant result was the significant reduction in opioid consumption during the first 24 hours, with a standardized mean difference (smd) of -2.07. this suggests that the use of magnesium has the potential to substantially decrease reliance on opioids for pain management in the early postoperative period. the observed effects of adjunctive magnesium sulfate in improving pain management in total knee arthroplasty (tka) may be attributed to several potential mechanisms. magnesium sulfate possesses pharmacological properties that could interact with pain pathways and opioid receptors, thereby modulating the analgesic response. one possible mechanism is the nmda receptor antagonism activity of magnesium sulfate. nmda receptors serve a crucial role in the formation and maintenance of central sensitization and chronic pain. by blocking nmda receptors, magnesium sulfate may attenuate the amplification of pain signals, resulting in reduced pain perception (52). this mechanism aligns with the significant reduction in postoperative pain observed in the early follow-up time points of our study. additionally, magnesium sulfate has been shown to possess calcium channel blocking properties (53). by inhibiting calcium influx, magnesium sulfate may reduce neuronal excitability and subsequent pain transmission (52). this modulation of calcium channels could contribute to the observed decrease in opioid consumption, as calcium signaling is involved in opioid receptor desensitization and tolerance development. moreover, magnesium sulfate has been reported to exhibit anti-inflammatory effects. inflammation is a crucial component of postoperative pain, and the anti-inflammatory properties of magnesium sulfate may help alleviate pain and reduce the need for rescue analgesics (54). these antiinflammatory effects may contribute to the short-time pain decreasing role of magnesium seen in this study. 5. strengths and limitations one of the strengths of this study is the inclusion of a comprehensive search strategy that yielded a substantial number of relevant studies. by employing a systematic approach, we were able to minimize selection bias and ensure a representative sample for our meta-analysis. another strength is the rigorous assessment of outcomes using standardized measures. the use of standardized protocols for data extraction and analysis increased the reliability and comparability of the results across studies. furthermore, the inclusion of multiple outcome measures, such as opioid consumption, postoperative pain scores, time to first analgesic, and adverse effects, allowed for a comprehensive evaluation of the effects of magnesium sulfate on various aspects of postoperative pain management. despite the strengths of this study, there are several limitations that should be acknowledged. first, the number of included studies was relatively small, particularly when subgroup analysis was attempted. the scarce number of studies in subgroups restricted our ability to conduct subgroup analyses based on factors such as route of administration or dosage of magnesium sulfate. second, the heterogeneity observed among the included studies may have influenced the overall findings. although random effects models were used to account for potential heterogeneity, variations in study design, patient populations, and intervention protocols could have contributed to the observed heterogeneity. furthermore, the risk of bias in the included studies should be considered. while efforts were made to include studies regardless of their risk of bias score, the presence of studies with high risk of bias or some concerns may have affected the overall reliability and validity of the findings. finally, based on grade, the moderate to low certainty of evidence for certain outcomes, such as opioid consumption and postoperative pain, shows that more studies are needed to strengthen the certainty in effect estimates. 6. future directions this study provides valuable insights into the role of magnesium sulfate in postoperative pain management following total knee arthroplasty. however, there are several avenues for future research that could further enhance our understanding and optimize the use of magnesium sulfate in clinical practice. first, given the limited number of studies available in this review, future research should aim to conduct large-scale, multicenter rcts to provide more robust evidence. investigathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 7 archives of academic emergency medicine. 2023; 11(1): e58 tions comparing different routes and dosages of magnesium sulfate administration could help identify the most effective and well-tolerated regimens, specifically in the tka setting. in addition to its analgesic properties, the potential impact of magnesium sulfate on other outcomes, such as functional recovery, patient satisfaction, and long-term complications, should be investigated. long-term follow-up studies assessing the durability of pain relief and the effects on joint function and quality of life would provide valuable information for clinical decision-making and patient counseling. moreover, the cost-effectiveness of magnesium sulfate in comparison to other analgesic modalities should be assessed. economic evaluations, such as cost-effectiveness or cost-utility analyses, could provide insights into the value of incorporating magnesium sulfate into perioperative pain management protocols. finally, the identification of potential biomarkers or predictors of response to magnesium sulfate could help personalize pain management strategies. genetic, proteomic, or phenotypic profiling studies could identify patient characteristics or biomarkers associated with a favorable response to magnesium sulfate, allowing for more targeted and individualized treatment approaches. 7. conclusion the findings of this study indicate that the addition of magnesium sulfate as adjunctive therapy in total knee arthroplasty improves pain management by reducing opioid consumption and alleviating postoperative pain during the early stages of recovery, without causing an increase in the adverse effects. however, considering the limitations of the included studies and the overall low to moderate certainty of the evidence, these results should be interpreted with caution. 8. declarations 8.1. acknowledgments none to declare. 8.2. conflict of interest the authors declare that they have no conflict of interest. 8.3. funding and support no funding or grants were obtained for this study. 8.4. authors’ contribution all authors made substantial contributions to the production of this work: • conception and design of the work: amirali azimi • acquisition, analysis, and data interpretation: amirali azimi, fatemeh-sadat tabatabaei, amirfarbod azimi, hamid mazloom • drafting and work revision: amirali azimi, amirfarbod azimi • agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: amirali azimi, fatemeh-sadat tabatabaei, amirfarbod azimi, hamid mazloom, mohammad mehdi foruzanfar and nastaran sadat mahdavi. 8.5. patient and public involvement patients were not involved in this research. 8.6. data sharing statement all data relevant to the study are included in this article or available in the supplemental file. the authors ensured that no patient-identifiable data are available. 8.7. ethical approval resulting from the study design (meta-analysis), an ethical approval is not applicable. 8.8. informed consent the study was not done 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jw, lahori a, merlo ja, gill o, ghoddoussi f, patel km, et al. adductor canal blocks with bupivacaine and magnesium after same-day discharge total knee arthroplasty improve postoperative pain relief and decrease opioid consumption a prospective randomized controlled trial. clin j pain. 2022;38(6):388-95. 46. morel v, pickering me, goubayon j, djobo m, macian n, pickering g. magnesium for pain treatment in 2021? state of the art. nutrients. 2021;13(5):1397. 47. muthiah t, arora mk, trikha a, sunder ra, prasad g, singh pm. efficacy of magnesium as an adjuvant to bupivacaine in 3-in-1 nerve block for arthroscopic anterior cruciate ligament repair. indian j anaesth. 2016;60(7):491-5. 48. schulz-stübner s, wettmann g, reyle-hahn s, rossaint r. magnesium as part of balanced general anaesthesia with propofol, remifentanil and mivacurium: a doubleblind, randomized prospective study in 50 patients. eur j anaesthesiol. 2001;18(11):723-9. 49. ko s-h, lim h-r, kim d-c, han y-j, choe h, song h-s. magnesium sulfate does not reduce postoperative analgesic requirements. anesthesiology. 2001;95(3):640-6. 50. jaoua h, zghidi sm, wissem l, laassili s, ammar n, ali j, et al. effectiveness of intravenous magnesium on postoperative pain after abdominal surgery versus placebo: double blind randomized controlled trial. tunis med. 2010;88(5):317-23. 51. xiang wn, jiang l, shi lt, jiang cm, zhou y, yang ch. the effect of magnesium added to bupivacaine for arthroscopy: a meta-analysis of randomized controlled trials. j orthop surg res. 2021;16(1):583. 52. soleimanpour h, imani f, dolati s, soleimanpour m, shahsavarinia k. management of pain using magnesium sulphate: a narrative review. postgrad med. 2022;134(3):260-6. 53. franzoni s, rossi sm, cassinadri a, sangaletti r, benazzo f. perioperative pain management in total knee arthrothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 10 plasty: a narrative review of current multimodal analgesia protocols. appl. sci. 2023; 13(6):3798. 54. lavand’homme pm, kehlet h, rawal n, joshi gp. pain management after total knee arthroplasty: procedure specific postoperative pain management recommendations. eur j anaesthesiol. 2022;39(9):743-57. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e58 table 1: baseline characteristics and method of intervention and control in the included studies authors ( year) country; study design sample size (n), general anesthesia focal analgesics intervention intervention route / magnesium dosage control route / control medication postoperative analgesia mean age (y), male (%) mg cg zhao et al. (2023) (22) china; rct 45 65.9 20 45 64.2 29 ga pai mgso4 + control medications pai / 250 mg mgso4 pai / ropivacaine, epinephrine dexamethasone, subcutaneous morphine; po celecoxib choi et al. (2022) (45) united states; rct 49 66.5 43 53 67.4 38 sa acb mgso4 + control medications acb / 150 mg (0.3 ml) mgso4 acb / bupivacaine not defined zoratto et al. (2021) (20) canada; rct 41 67.5 54 39 66.7 54 sa pai mgso4 + control medications acb / 2 g mgso4 acb / ropivacaine pca iv morphine; po acetaminophen; po celecoxib zhao et al. (2021) (21) china; rct 30 69.6 36 30 69.8 40 sa pai mgso4 + control medications pai / 250 mg mgso4 pai / levobupivacaine, triamcinolone pca iv sufentanil and dezocine park et al. (2020) (42) sout korea; ros 115 72.2 13.9 115 72.2 13 sa fnb mgso4 iv / bolus 50 mg/kg infusion 15 mg/kg.h iv / normal saline pca iv fentanyl; po acetaminophen, celecoxib, pregabalin; rescue iv opioids shin et al. (2016) (41) sout korea; rct 22 74.3 4.8 22 72.3 0 sa fnb pai mgso4 iv / bolus 50 mg/kg infusion 15 mg/kg.h iv / normal saline pca iv fentanyl; po acetaminophen, celecoxib, pregabalin; iv ketoprophen frassanito et al. (2015) (23) italy; rct 20 65.6 40 20 67.4 25 sa mgso4 iv / bolus 40 mg/kg infusion 10 mg/kg.h iv / normal saline pca iv morphine; iv paracetamol; iv ketorolac daabiss et al. (2015) (44) saudi arabia; rct 40 61.1 50 40 59.5 57 ea mgso4 + control medications epidural catheter / bolus 50 mg mgso4 infusion 10 mg/h epidural catheter / bupivacaine pca epidural fentanyl; im pethidine elmawgoud et al. (2008) (43) egypt; rct 20 55 35 20 55 60 ga fnb mgso4 + control medications fnb / bolus 1.5 g mgso4 infusion 0.3 g/h fnb / ropivacaine pca iv morphine rct: randomized clinical trial; ros: retrospective observational study; mg: magnesium group; cg: control group; ga: general anesthesia; sa: spinal anesthesia; pai: periarticular infiltration; fnb: femoral nerve block; ea: epidural anesthesia; iv: intravenous; acb: adductor canal block; pca: patient-controlled analgesia; mgso4: magnesium sulfate; po: oral; im: intramuscular. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 12 figure 1: flowchart depicting the study selection process. wos: web of science; tka: total knee arthroplasty; rct: randomized clinical trial. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 13 archives of academic emergency medicine. 2023; 11(1): e58 figure 2: forest plot presenting the effect of adjunctive magnesium sulfate on opioid consumption in four subgroups by timing. po: post operation; sd: standard deviation; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 14 figure 3: forest plot presenting the effect of adjunctive magnesium sulfate on postoperative pain in five subgroups by timing. po: post operation; sd: standard deviation; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 15 archives of academic emergency medicine. 2023; 11(1): e58 figure 4: forest plot illustrating the effect of adjunctive magnesium sulfate on time to first rescue analgesic. sd: standard deviation; ci: confidence interval. figure 5: forest plot for adverse effects reported in the included studies. this figure presents the risk ratio analysis for the occurrence of nausea and pruritus.ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 16 figure 6: risk of bias assessment summary using the revised cochrane collaboration tool (rob 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 17 archives of academic emergency medicine. 2023; 11(1): e58 supplementary figure s 1: funnel plot for opioid consumption by subgroups. po: post operation; ci: confidence interval. supplementary table s 1: secondary outcomes not included in the quantitative analysis outcome study id magnesium group control group reported statistical significance magnesium compared to control knee rom degree pod 1 zhao et al. (2023) 89.0 ± 6.3 87.0 ± 9.0 p-value = 0.465 not superior degree pod 2 zhao et al. (2023) 95.8 ± 5.1 95.3 ± 7.3 p-value = 0.834 not superior degree pod 3 zhao et al. (2023) 106.1 ± 5.0 104.7 ± 7.2 p-value = 0.258 not superior degree 3 months zhao et al. (2023) 117.9 ± 4.8 115.7 ± 6.2 p-value = 0.099 not superior length of hospital stay hours zhao et al. (2023) 68.4 ± 3.2 69.4 ± 3.0 p-value = 0.160 not superior days zoratto et al. (2021) 2.2 [2.0–3.1] 2.1 [1.9–3.9] p-value = 0.550 not superior satisfaction with pain control categorical (excellent) zoratto et al. (2021) 13 (38) 12 (38) p-value = 0.320 not superior likert scale choi et al. (2022) 8.8 ±2.0 8.7 ±1.8 p-value = 0.837 not superior likert scale frassanito et al. (2015) 8.9±0.1 8.8±0.2 p-value = 0.060 not superior pod: post-operative day; rom: range of motion. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index a. azimi et al. 18 supplementary figure s 2: funnel plot for postoperative pain by subgroups. po: post operation; ci: confidence interval. supplementary table s 2: quality of the evidence assessed using grade (grading of recommendations, assessment, development and evaluations) scoring system outcome of interest risk of bias imprecision inconsistency indirectness publication bias quality of the evidence (grade) opioid consumption serious limitations no serious limitations serious limitations no serious limitations no serious limitations • • ◦ ◦ low postoperative pain serious limitations no serious limitations serious limitations no serious limitations no serious limitations • • ◦ ◦ low time to first analgesic serious limitations no serious limitations no serious limitations no serious limitations no serious limitations • • • ◦ moderate adverse effects serious limitations no serious limitations no serious limitations no serious limitations no serious limitations • • • ◦ moderate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 19 archives of academic emergency medicine. 2023; 11(1): e58 supplementary figure s 3: funnel plot for time to first rescue analgesic. ci: confidence interval. supplements 1: search strategy medline (via pubmed) 1. “arthroplasty, replacement, knee”[mh] or “hemiarthroplasty”[mh] or “knee arthroplasties”[tiab] or “knee arthroplasty”[tiab] or “knee reconstruction”[tiab] or “knee joint replacement”[tiab] or “knee surgery”[tiab] or “knee surgeries”[tiab] or “knee replacement”[tiab] or “knee replacements”[tiab] or “total knee arthroplasty”[tiab] 2. “magnesium”[mh] or “magnesium sulfate”[mh] or “magnesium compounds”[mh] or “magnesium chloride”[mh] or “magnesium hydroxide”[mh] or “magnesium”[tiab] or “magnesium sulfate”[tiab] or “mgso4”[tiab] or “magnesium compounds”[tiab] or “magnesium chloride”[tiab] or “mgcl2”[tiab] or “magnesium hydroxide”[tiab] or “mg(oh)4”[tiab] 3. #1 and #2 embase: 1. ‘knee surgery’/exp or ‘knee arthroplasty’/exp or ‘knee replacement’/exp or ‘total knee arthroplasty’/exp or ‘knee arthroplasty’:ab,ti or ‘knee reconstruction’:ab,ti or ‘knee joint replacement’:ab,ti or ‘knee surgery’:ab,ti or ‘knee surgeries’:ab,ti or ‘knee replacement’:ab,ti or ‘knee replacements’:ab,ti or ‘total knee arthroplasty’:ab,ti 2. ‘magnesium’/exp or ‘magnesium sulfate’/exp or ‘magnesium chloride’/exp or ‘magnesium’:ab,ti or ‘magnesium sulfate’:ab,ti or ‘mgso4’:ab,ti or ‘magnesium compounds’:ab,ti or ‘magnesium chloride’:ab,ti or ‘mgcl2’:ab,ti or ‘magnesium hydroxide’:ab,ti or ‘mg(oh)4’:ab,ti 3. #1 and #2 scopus: 1. title-abs-key(“knee arthroplasties” or “knee arthroplasty” or “knee reconstruction” or “knee joint replacement” or “knee surgery” or “knee surgeries” or “knee replacement” or “knee replacements” or “total knee arthroplasty”) 2. title-abs-key(“magnesium” or “magnesium sulfate” or “mgso4” or “magnesium compounds” or “magnesium chloride” or “mgcl2” or “magnesium hydroxide” or “mg(oh)4”) 3. #1 and #2 web of science ( wos): 1. ts=(“knee arthroplasties” or “knee arthroplasty” or “knee reconstruction” or “knee joint replacement” or “knee surgery” or “knee surgeries” or “knee replacement” or “knee replacements” or “total knee arthroplasty”) 2. ts=(“magnesium” or “magnesium sulfate” or “mgso4” or “magnesium compounds” or “magnesium chloride” or “mgcl2” or “magnesium hydroxide” or “mg(oh)4”) 3. #1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion strengths and limitations future directions conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 162 emergency (2015); 3 (4): 162-164 casr report third ventricle colloid cyst as a cause of sudden drop attacks of a 13-yearold boy behzad zohrevandi, vahid monsef kasmaie*, payman asadi, hosna tajik guilan road trauma research center, guilan university of medical sciences, rasht, iran *corresponding author: vahid monsef kasmaie; road trauma research center, guilan university of medical sciences, rasht, iran. tel: +989113344071. fax: +981313238373; email: vmonsef@yahoo.com received: december 2014; accepted: december 2014 abstract colloid cysts are mucous-filled masses with an outer fibrous layer. these cysts are rare developmental malformation and not a true neoplasm. they usually found incidentally and are asymptomatic; but in some cases may associate with rapid neurologic deterioration, herniation, and sudden death. recognition of this rare but important diagnosis may result in decreasing mortality. in this report, we presented a 13-year-old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle. key words: colloid cyst; sudden death; hydrocephalus cite this article as: zohrevandi b, kasmaie bm, asadi p, tajic h. third ventricle colloid cyst as a cause of sudden drop attacks of a 13-year-old boy. emergency. 2015;3(4):162-4. introduction: olloid cysts are mucous-filled masses with an outer fibrous layer. these cysts are rare developmental malformation and not a true neoplasm. they are congenital benign tumor accounting for 15-20 % of intraventricular mass but only about 1% of intracranial ones (1-3). they can be diagnosed at any age but usually become symptomatic in the third to sixth decades and more common in men than women. they usually found incidentally and are asymptomatic; but in some instances may associate with rapid neurologic deterioration, herniation, and sudden death. so, recognition of this rare but important diagnosis may result in decreasing mortality (4). in this report, we presented a 13-year-old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle. case report: a 13-year-old boy was brought to the emergency department (ed) with complaint of two times drop attack. the patient mentioned that he felt sudden weakness in both lower limbs, which led to drop. he did not lose his consciousness before, during, or after dropping. these attacks were happened about 4 hours before admission and he did not have any same experience previously. he did not have complaint of nausea, vomiting, headache, vertigo, blurred vision, or palpitation. the subject did not have any known structural or congenital heart disease, but suffered from asthma and used salbutamol spray irregularly. the patient did not have trauma history and there was no positive history of any known medical illness in his parents or closed relatives. on arrival, he had 36.9°c axillary temperature, 16/minute respiratory rate, 90/minute pulse rate, 120/80 mmhg blood pressure, and 96% oxygen saturation at room air. on physical examination, he did not have focal neurologic findings or even paresthesia or paraplegia. general examination of head and neck, chest, abdomen, and limbs did not reveal any positive findings. an electrocardiogram (ecg) showed normal sinus rhythm without any obvious abnormality. all biochemistry parameters were reported as normal range. following the evaluation process, a brain computed tomography (ct) was performed (figure-1). a hyperdense round lesion was seen in the third ventricle consequently caused that the corresponding physician requested a neurologic consultation in the ed. finally, the brain magnetic resonance imaging (mri) confirmed the diagnosis of third ventricle colloid cyst and the patient was underwent surgery and discharged without any problem (figure 2). discussion: the colloid cysts commonly settle near the foramen of monro in the anterior third ventricle and so may encounter with drainage of the cerebrospinal fluid (csf) (3). since even a small lesion can block the mentioned foramen, these cysts may result in hydrocephalus and increase the intra cranial pressure (5). increased intracranial pressure can be manifested with headache c this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 163 zohrevandi et al described as severe and intermittent, with short duration, usually located frontally. in contrast with usual headaches, secondary to intracranial tumors, the colloid cyst induced headache can be relieved by lying down (4). other symptoms include drop attacks, gait abnormalities, progressive dementia, and transient loss of consciousness. in children, the most common symptoms are nausea, vomiting, headache, diplopia, and papilledema (6). the classic clinical description of intermittent headaches and drop attacks occurs in only one-third of patients. sudden obstruction of the ventricular system and following rapid rising of intracranial pressure can lead to herniation and rarely sudden death (7, 8). colloid cysts size varies from 3-40 millimeters in diameter, but the size do not related to their symptoms or outcome, as even small ones may lead to sudden death (9). colloid cyst is usually diagnosed by non-contrast computed tomography (ct) as an oval or rounded hyperdense mass on the anterior aspect of the third ventricle. they may occasionally be hypodense or isodense to the brain, or found in other areas of the brain. colloid cysts have different manifestation on mri. despite their variable signal characteristics, their location and shape help to the correct preoperative diagnosis in most patients (6). half of the cases are hyperintense on t1-weighted mri images and hypointense on t2-weighted mri images respected to brain. isointense cysts are not easily identified on mri, and in such instances ct scan is more useful (9, 10). early detection and excision of the colloid cyst carry the best prognosis. surgical excision is curative but challenging due to its location. small asymptomatic colloid cyst can be considered for close follow up by serial examinations and neuroimaging (11). there is also the rare report of spontaneous resolving of the third ventricle colloid cyst (12, 13). acknowledgments: none conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. humphries rl, stone ck, bowers rc. colloid cyst: a case report and literature review of a rare but deadly condition. j emerg med. 2011;40(1):e5-e9. 2. uhlmann ej, norden ad. rare tumors. primary central nervous system tumors: springer; 2011. p. 499-528. 3. ho-fung v, jaimes c, pollock an. third ventricular colloid cyst. pediatr emerg care. 2011;27(3):242-3. 4. spears rc. colloid cyst headache. curr pain headache rep. 2004;8(4):297-300. 5. symss np, ramamurthi r, kapu r, et al. complication avoidance in transcallosal transforaminal approach to colloid figure 1: flair sequences of brain magnetic resonance imaging figure 1: axial brain computed tomography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (4): 162-164 164 cysts of the anterior third ventriclen: an analysis of 80 cases. asian j neurosurg. 2014;9(2):51-7. 6. armao d, castillo m, chen h, kwock l. colloid cyst of the third ventricle: imaging-pathologic correlation. am j neuroradiol. 2000;21(8):1470-7. 7. black m, graham d. sudden unexplained death in adults caused by intracranial pathology. j clin pathol. 2002;55(1):4450. 8. ravnik j, bunc g, grcar a, zunic m, velnar t. colloid cysts of the third ventricle exhibit various clinical presentation: a review of three cases. bosn j basic med sci. 2014;14(3):132-5. 9. mamourian ac, cromwell ld, harbaugh re. colloid cyst of the third ventricle: sometimes more conspicuous on ct than mr. am j neuroradiol. 1998;19(5):875-8. 10. maeder pp, holtås s, basibüyük l, salford lg, tapper u, brun a. colloid cysts of the third ventricle: correlation of mr and ct findings with histology and chemical analysis. am j neuroradiol. 1990;11(3):575-81. 11. desai ki, nadkarni td, muzumdar dp, goel ah. surgical management of colloid cyst of the third ventricle—a study of 105 cases. surg neurol. 2002;57(5):295-302. 12. annamalai g, lindsay k, bhattacharya j. spontaneous resolution of a colloid cyst of the third ventricle. br j radiol. 2008 81(961):e20-2. 13. alnaghmoosh n, alkhani a. colloid cysts in children, a clinical and radiological study. childs nerv syst. 2006;22(5):514-6. introduction: case report: discussion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: archives of academic emergency medicine. 2019; 7 (1): e40 le t t e r to ed i to r the role of foley catheter coated with gold, silver, and palladium in decreasing urinary tract infections in the intensive care unit; a letter to editor seyed hossein ardehali1, maryam sedaghatmanesh2, alireza fatemi3∗ 1. department of anesthesiology and critical care, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. internal medicine department, shohadaye tajrish hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: may 2019; accepted: june 2019; published online: 27 july 2019 cite this article as: the role of foley catheter coated with gold, silver, and palladium in decreasing urinary tract infections in the intensive care unit; a letter to editor. arch acad emerg med. 2019; 7(1): e40. urinary tract infections (utis) are among the most common hospital-acquired infections, which are caused by urinary catheterization in most cases (1, 2). these infections, like other hospital-acquired infections, elongate the duration of hospitalization and can act as a depot for antibiotic-resistant bacteria. for each day that the catheter remains in the urinary tract, the probability of uti increases by 3% to 7% (3). in 2011, the centers for disease control and prevention (cdc) reported the rate of catheter-related uti in the intensive care unit (icu) as 1.2 to 4.5 cases per 1000 catheters per day and the mortality rate related to these infections has been estimated to be about 15% (4). various approaches have been proposed for decreasing these infections. among these approaches, using aseptic methods, limiting the use of catheters to necessary cases, using disposable tools, and training the personnel can be pointed out. one of the most recent methods suggested in this regard is using catheters coated with anti-septic agents, antibiotics, and agents and metals such as silver, silicon, nitrofurazone (5, 6). in a study in 24 hospitals, using catheters coated with silicone-nitrofurazone compounds led to a slight decrease in uti rate with odds ratio of 0.68 (5). in another study in the united kingdom, the decreasing effect of nitrofurazonecoated catheters on utis caused by foley catheters was confirmed (6). a study on 116 patients in spain revealed 38% decrease in the rate of utis caused by catheters in urinary tract when using catheters coated by gold, silver, and palladium ∗corresponding author: alireza fatemi; men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. tel: 00989128949858, email: dr_fatemi_alireza@yahoo.com . (7). fortunately, this kind of catheter has become available to the physicians in iran. however, since enough experience does not exist regarding their possible harms and benefits in the iranian population, the researchers of the present study attempted to design a case-control study for evaluating the effects of using urinary catheters coated with gold, silver, and palladium on the rate of infections and mortality due to utis in patients hospitalized in the icu of a teaching hospital in tehran, iran. inclusion criteria were age over 18 years and having a catheter for 2 to 7 days. presence of any infection or antibiotic consumption at the time of catheterization or development of an infection not related to the catheter during the study, the patient being pregnant or lactating, and having a history of allergy to the metal compounds of the catheter were among the exclusion criteria. positive urine culture was defined as presence of at least 100000 bacterial colonies in each milliliter. finally, 314 patients were randomly divided into 2 groups of 157 and catheterized with either regular or metal coated catheters. the 2 groups were similar regarding sex distribution (p = 0.518). mean age of the patients was 59.80 ± 19.85 years in those with metal coated catheters and 61.69 ± 19.57 years in the regular catheter group (p = 0.396). throughout the study, 26 (16.6%) patients in the coated catheter group developed symptoms related with uti due to catheter, 18 (11.4%) of which had positive urine cultures (9 cases of klebsiella pneumoniae, 3 cases of escherichia coli, 4 cases of pseudomonas aeruginosa, and 2 cases of klebsiella oxytoca). all the mentioned microorganisms were resistant to fluoroquinolone family, aminoglycosides, penicillin, third and fourth generation cephalosporins, carbapenems and colistin. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h. ardehali et al. 2 in the non-coated group, 38 (24.2%) patients developed symptoms related to uti due to catheterization, 29 (18.5%) of which were reported as positive (17 cases of klebsiella pneumoniae, 7 cases of escherichia coli, and 5 cases of pseudomonas aeruginosa). all the mentioned microorganisms were resistant to fluoroquinolone family, aminoglycosides, penicillin, third and fourth generation cephalosporins, carbapenems and colistin. there was no statistically significant difference between the 2 groups regarding developing uti (p = 0.134). additionally, no significant difference was found between the coated and non-coated groups regarding infection-related mortality (6 (3.8%) patients in the coated groups vs. 11 (7.0%) in the non-coated group; p > 0.05). based on the findings of the present study, although the group using heavy metal coated urinary catheters had a lower number of infections and mortality cases, this difference was not statistically significant. therefore, we should be cautious regarding suggesting their use considering the price of these catheters and their availability in hospitals. it seems that more accurate and multicenter studies with controlling other probable confounding factors are required for reaching a final decision regarding the use of this tool. 1. appendix 1.1. acknowledgements hereby, we thank the icu staff members of shohadaye tajrish hospital for their hearty cooperation and helping us perform this study. 1.2. author’s contribution all the authors met the 4 criteria recommended by the international committee of medical journal editors for gaining authorship. authors orcids seyed hossein ardehali: 0000-0002-7662-0551 alireza fatemi: 0000-0003-0671-7611 1.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support this study was supported by bactiguard through providing gold, silver, and palladium coated urinary catheters for patients. references 1. saint s, chenoweth ce. biofilms and catheter-associated urinary tract infections. infectious disease clinics of north america. 2003;17(2):411-32. 2. weber dj, sickbert-bennett ee, gould cv, brown vm, huslage k, rutala wa. incidence of catheter-associated and non-catheter-associated urinary tract infections in a healthcare system. infection control & hospital epidemiology. 2011;32(8):822-3. 3. tambyah pa, maki dg. catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1497 catheterized patients. archives of internal medicine. 2000;160(5):678-82. 4. dudeck ma, horan tc, peterson kd, allen-bridson k, morrell g, anttila a, et al. national healthcare safety network report, data summary for 2011, deviceassociated module. american journal of infection control. 2013;41(4):286-300. 5. pickard r, lam t, maclennan g, starr k, kilonzo m, mcpherson g, et al. antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. the lancet. 2012;380(9857):192735. 6. pickard r, lam t, maclennan g, starr k, kilonzo m, mcpherson g, et al. types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial-and antiseptic-impregnated urethral catheters (the catheter trial). health technology assessment. 2012. 7. hidalgo if, rebollo mp, planas mc, barbero mc. incidence of urinary tract infections after cardiac surgery: comparative study accordind to catheterization device. enfermeria intensiva. 2015;26(2):54-62. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 104 emergency (2014); 2 (2): 104-105 photo quiz confusing hypoxia in a 21-year-old intubated multiple trauma patient parvin kashani1, sahar mirbaha2* 1. department of emergency medicine, loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran figure1: spiral axial chest computed tomography scan  cite this article as: kashani p, mirbaha s. confusing hypoxia in a 21-year-old intubated multiple trauma patient. emergency. 2014;2 (2): 104-5. case presentation:1 21-year-old man was brought to the emergency department due to multiple trauma (mt) caused by a motor-car accident (mca). on arrival, the patient was intubated by prehospital emergency medical services (ems) and had a glasgow coma scale (gcs) score of 6 on 10 (due to intubation, verbal score was omitted). physical examination revealed blood pressure of 150/70 mmhg, oxygen saturation (o2sat) of 60%, and pulse rate of 110/min. examination of the tracheal tube site revealed incorrect esophageal placement. the patient was intubated again and his o2sat improved and reached approximately 96%. his pupils were reactive and of the same size. the doll’s eye was normal, and plantar reflex was neuter in both sides. neither *corresponding author: sahar mirbaha; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. mobile phone: +989121549405; phone/fax: +982122721155. email: mirsa317@yahoo.com received: 1 april 2014; accepted: 9 april 2014 expanding hematoma nor emphysema was observed in his neck. laceration was noted on his left ear, but otorrhagia and tympanic perforation were not found. the lung sounds were normal in both sides. extended focused abdominal sonography for trauma (e-fast) examination revealed the absence of free fluid in the abdomen and pericardial space. no deformity of limbs was noted and the distal pulses were palpable. the patient’s o2sat decreased during his admission to the emergency department, and further examination indicated obvious decreased sound in his right lung that could not be reversed by needle thoracostomy. on reviewing his previous chest computed tomography, an obvious questionable pathology was detected in his right side figure 1. what is your diagnosis? a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 105 kashani and mirbaha diagnosis: massive blood clot in right main bronchus case fate: there was a transaction in the right bronchus path, which required pushing of the tracheal tube to the right bronchus and passing of the suction catheter through it. a big clot was evicted and the patient’s o2sat improved dramatically. discussion: the occurrence of respiratory distress is serious. the mortality rate of traumatic patients presenting to the emergency department with respiratory distress is approximately 50% (1). the causes of hypoxia occurring soon after intubation can be found in the acronym “dopes,” which denotes displacement of the endotracheal tube (ett); obstruction of ett; pneumothorax, pulmonary embolism, and pulmonary edema; equipment and ventilator problems; and, finally, stacked breaths (2-4). the most important issues that should be checked when this problem is detected are as follows: first, the severity of the problem should be determined (do you need to start immediate resuscitation?) and then mash, i.e., movement of the chest during ventilation, arterial blood gas (abg) sample, the skin color of the patient, and hemodynamic stability, should be assessed (2, 5, 6). the ventilator must be disconnected and high-flow 100% oxygen should be administered using a bag valve. after ruling out tension pneumothorax, the other possible causes should be considered (2, 4). a responsible physician should determine whether the problem is related to ett or the patient. to ensure the right place of ett, the end tidal co2 (etco2) should be checked. in addition, to ensure that ett is not obstructed, a suction catheter and/or a bougie can be passed through it. the placement of ett must be visually checked, preferably by bronchoscopy, or alternatively, by laryngoscopy, from the top end (although this is far from 100% reliable). if hypoxemia is not critical, particularly, if endobronchial intubation is suspected, then chest radiography should be considered to check the ett position (5, 6). airway obstruction may be related to different factors, including kinking or bending of ett; tube obstruction with foreign bodies, mucus, blood, etc.; and extrinsic compression (3, 6). severe mucus plugging may redound to worsen gas exchange, increasing inspiratory pressure and causing difficulty in breathing, and if not treated quickly, it may cause infectious complications and mortality (4, 7). furthermore, establishing good hydration, damping of inspired gases, chest physiotherapy, and postural drainage plus manual lung hyperinflation are considered as traditional and safe methods for the prevention and treatment of atelectasis in most of the patients (5, 7). acknowledgment: we would like to express our special thanks from emergency department staffs. conflict of interest: there was no conflict of interest. author’s contribution: all authors contributed in drafting /revising the manuscript, study concept or design, and interpretation of data. references: 1. alimohammadi h, baratloo a, abdalvand a, rouhipour a, safari s. effects of pain relief on arterial blood o2 saturation. trauma mon. 2014;19(1):e14034. 2. stone rh, bricknell ss. experience with a new device for clearing mucus from the endotracheal tube. respir care. 2011;56(4):520-2. 3. johnson km, lehman re. acute management of the obstructed endotracheal tube. respir care. 2012;57(8): 1342-4. 4. hofstetter c, scheller b, hoegl s, mack mg, zwissler b, byhahn c. cuff overinflation and endotracheal tube obstruction: case report and experimental study. scand j trauma. 2010;18:18. 5. hagberg c, georgi r, krier c. complications of managing the airway. best pract res clin anaesthesiol. 2005;19(4):641-59. 6. varga s, shupp jw, maher d, tuznik i, sava ja. trauma airway management: transition from anesthesia to emergency medicine. j emerg med. 2013;44(6):1190-5. 7. suljević i, beharić s, šurković i. complications in preserving the airway in intensive care unit patients. acta clin croat. 2012;51(3.):519-24. archives of academic emergency medicine. 2019; 7 (1): e54 le t t e r to ed i to r a polyvinyl chloride eraser as a surface marker for computed tomography in emergency imaging; a letter to editor yuya murakami1, taihei yamada1, hiromichi naito1∗ 1. department of emergency, critical care and disaster medicine, okayama university hospital, okayama, japan. received: july 2019; accepted: august 2019; published online: 28 september 2019 cite this article as: murakami y, yamada t, naito h. a polyvinyl chloride eraser as a surface marker for computed tomography in emergency imaging; a letter to editor. arch acad emerg med. 2019; 7(1): e54. dear editor, in the wake of recent progress in computed tomography (ct) enabling to obtain high quality images within five minutes, ct scan has been widely used in emergency diagnostic radiology and is considered best suited for detection of pathologies, as well as assessing the location and extent of lesions in the emergency department. emergency physicians often require confirmation of surface bruises or wounds coexisting with pathology on ct scan. alternatively, they may want to confirm the presence or absence of pathology in the painful lesion. the use of an appropriate surface marker on the skin surface of the painful lesion may enable them to identify areas of interest and safely reduce radiation exposure. ct skin markers detected as virtually artifact-free and opaque, particularly for mammography, have been commercially available from several healthcare companies, but these markers are expensive ($57-$86 usd) and may not be easily accessible. most metal objects cause artifacts through multiple mechanisms, including beam hardening, scatter, and poisson noise, although some can be reduced using iterative reconstruction or by combining data from multiple scans (1). we found that a polyvinyl chloride eraser may be the best surface marker for ct marking applications. as shown in figure 1, a polyvinyl chloride eraser is visualized as a high-density, artifact-free homogenous object on ct scan and can be used as a skin surface marker in the emergency setting. interestingly, an eraser impacted in the nose of a five-year-old girl was reported to be identified as a calcified nodular mass by ∗corresponding author: hiromichi naito; emergency department, critical care and disaster medicine, okayama university graduate school of medicine dentistry and pharmaceutical sciences, 2-5-1 shikata-cho, kita-ku, okayama-shi, okayama, 700-8558, japan. email: qq-nakao@okayama-u.ac.jp, naito05084@gmail.com, tel: +81-86-235-7426, fax: +81-86-235-7427. figure 1: computed tomography scan of the chest revealed correspondence of rib fracture (arrowhead) and pain location, marked with an eraser (arrow). ct, which was diagnosed as rhinoliths. thus, an eraser is detected as a high-density and opaque object without artifacts (2, 3). in conclusion, a polyvinyl chloride eraser, inexpensive and easily available in the stationery section of retail stores, even in developing countries, can serve as a suitable surface marker for ct examination in an emergency setting to localize pathology from the skin surface. this study protocol was approved by ethical committee of okayama university hospital. 1. appendix 1.1. acknowledgements the staff members of department of emergency, critical care and disaster medicine, okayama university hospital this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem y. murakami et al. 2 are thanked for their cooperation in performance of this study. 1.2. author’s contribution ym and th performed the procedure. hn wrote the manuscript and edited the manuscript. all authors read and approved the final manuscript. authors orcids hiromichi naito: 0000-0002-7308-1716 taihei yamada: 0000-0001-7575-0365 1.3. conflict of interest the authors declare that they have no competing interests. 1.4. funding and support none. references 1. wellenberg rhh, hakvoort et, slump ch, boomsma mf, maas m, streekstra gj. metal artifact reduction techniques in musculoskeletal ct-imaging. eur j radiol. 2018;107:609. 2. munoz a, pedrosa i, villafruela m. "eraseroma" as a cause of rhinolith: ct and mri in a child. neuroradiology. 1997;39(11):824-6. 3. mukherji sk, castillo m, sarangi s, jacoway j. "eraseroma" in a nasal cavity. ajr am j roentgenol. 1996;166(3):727. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 78 emergency (2015); 3 (2): 78-80 case report periampullary diverticulum perforation following endoscopic retrograde cholangiopancreatography (ercp); a case report li-wei lin1, chin-chu wu2, lee-won chong3, aming chor-ming lin1,4,5* 1. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. department of medical imaging, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. department of gastroenterology, shin kong wu ho-su memorial hospital, taipei, taiwan. 4. department of intensive care unit, shin kong wu ho-su memorial hospital, taipei, taiwan. 5. school of medicine, fu-jen catholic university, new taipei city, taiwan. *corresponding author: aming chor-ming lin; emergency department, shin kong wu ho-su memorial hospital, 95 wen chang rd, taipei 111 taiwan, school of medicine, fu-jen catholic university, new taipei city, taiwan. tel: +886-02-28332211 ext 2082; fax: +886-02-28353547; email: amingphd@yahoo.com.tw, m002001@ms.skh.org.tw received: october 2014; accepted: november 2014 abstract endoscopic retrograde cholangiopancreatography (ercp) is widely used for the diagnosis and treatment of biliary and pancreatic tract disease. perforation is a rare complication of it, but it is associated with high rate of mortality, an overall mortality rate of 1.0-1.5%. here, a case of massive subcutaneous emphysema following ercp was reported without an obvious retroperitoneal or peritoneal perforation. key words: cholangiopancreatography, endoscopic retrograde; subcutaneous emphysema; pneumomediastinum, diagnostic cite this article as: lin lw, wu cc, chong lw, chor-ming lin a. periampullary diverticulum perforation following endoscopic retrograde cholangiopancreatography (ercp); a case report. emergency. 2015;3(2):78-80. introduction: ndoscopic retrograde cholangiopancreatography (ercp) is widely used for the diagnosis and treatment of biliary and pancreatic tract disease (1). although this is considered as a safe diagnostic tool, if operated by experts, it still carries a significantly high rate of complications including hemorrhage, perforation, infection, pancreatitis and cardiopulmonary events. perforation is a rare complication, but it is associated with high rate of mortality, an overall mortality rate of 1.01.5% (2). here, a case of massive subcutaneous emphysema following ercp was reported without an obvious retroperitoneal or peritoneal perforation. case presentation: a 94-year old woman was presented to the emergency department (ed) because of general weakness, abdominal pain, and dyspepsia for 4 days. she had diabetes mellitus, chronic atrial fibrillation, hypertension, and coronary artery disease with multi-vessel stenting in her medical history. the patient’s vital sign at the admission time included blood pressure of 182/86 mmhg, heart rate of 78 beats/minute, respiratory rate of 22 beats/minute, and oxygen saturation of 97% on room air. she was afebrile and physical examination showed the abdominal right upper quadrant tenderness without peritoneal signs. the rest of physical examinations were unremarkable. abdominal ultrasonography demonstrated on a small gallbladder without gallstone as well as dilatation of the main bile duct and bilateral intra-hepatic ducts. the complete blood cell count showed the following results: leukocyte count 5100/mm3 with 77.8% of segmented neutrophils, hemoglobin 12 gram/deciliter, and platelet 180000/microliter. other laboratory findings included: glucose 134 milligram/deciliter, blood urea nitrogen (bun) 24 milligram/deciliter, serum creatinine 1.8 milligram/deciliter, sodium 134 milliequivalent/liter, potassium 3.8 milliequivalent/liter, serum glutamic oxaloacetic transaminase (sgot) 26 unit/liter, albumin 3.5 gram/deciliter, total bilirubin 1.0 milligram/deciliter, lipase 31 unit/liter, and with an international normalized ratio (inr) of 1.52. with assumption of obstructive biliary tract process, the patient underwent ercp. during cannulation of the bile duct, a guidewire was applied to enter via the ampulla of vater. in spite of iatrogenic penetrating of a periampular diverticulum in the first try (figure 1), the guidewire was inserted into the bile duct for sphincterotomy, intraductal ultrasonography, biopsy, and stenting. the final diagnosis was distal common bile duct stenosis. due to old age and comorbidities of the patient, she was shifted to the ed for more observation. after 2 hours, patient became symptomatic with dyspnea and abdominal pain. repeated physical examination revealed generalized subcutaneous emphysema with extensive puffiness and e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 79 li-wei et al figure 1: endoscopic view shows guidewire (arrow) perforation of a periampullary diverticulum. palpable crepitation in all over the body from head to the extremities. she had mild fever and abdominal distention without any peritoneal signs. her oxygen saturation was 94% on room air. laboratory test results showed leukocyte count of 18400/mm3 with left shift. the whole body computed tomography (ct) scan revealed extensive subcutaneous emphysema (figure 2). since there was no evidence of either contrast leakage from the biliary tract or fluid collections in the peritoneal and retroperitoneal cavity, she was conservatively managed with oxygen supplement, nasogastric tubing, parenteral nutrition, and broad-spectrum antibiotics. the patient responded well and gradual resolution of the subcutaneous emphysema was happened after 9 days. discussion: the presence of subcutaneous emphysema following ercp is an uncommon but well-recognized complication. the most common cause of this problem is duodenal perforation resulting in retroperitoneal collections of free air. perforation is now reported in less than 1% of ercps with sphincterotomy (3). periampullary diverticulum perforation during ercp is the rarest complication, which is usually manifested by abdominal pain, fever, leukocytosis, and hemodynamic compromise. a high index of suspicion is required for timely correct diagnosis of ercp-related perforations because of signs and symptoms, often mimic other intra-abdominal processes (4, 5). retroperitoneal air may spread through the fascial planes to the subcutaneous space or dissect into the peritoneal or pleural cavities, resulting in pneumoperitoneum, pneumothorax, or pneumomediastinum. this manifestation is known as ginkgo sign (6). isolated neck and scrotal subcutaneous emphysema as well as cases of generalized subcutaneous emphysema extended to the figure 2: computed tomography scan (coronal view) shows extensive subcutaneous emphysema. contrast retention in the common bile duct (arrow) after ercp is also shown without evidence of leakage. face, neck, trunk, and upper extremities have been reported (7). in such situation, the first imaging study is usually an abdominal x-ray. ct scans can help assessing contrast leakage and identify any retroperitoneal or intraperitoneal free air (8). the treatment outcome depends on clinical manifestations and the type and severity of the leak (9). although patients with perforations may be conservatively treated perforations, which are remote from the papilla and those with free contrast extravasation with or without evidence of sepsis may need surgical intervention (10-12). this case shows that periampullary diverticulum perforation secondary to ercp may be managed conservatively with intravenous fluid therapy, broad-spectrum antibiotics, nasogastric tube decompression, and parenteral nutrition. acknowledgment: none. conflict of interest: none. funding support: none. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (2): 78-80 80 references: 1. rhim ad, kochman ml. a young woman with gallstone pancreatitis and abnormal liver tests: when is endoscopic retrograde cholangiopancreatography needed? clinical gastroenterology and hepatology: the official clinical practice journal of the american gastroenterological association. 2008;6(7):741-5. 2. guideline a. complications of ercp. gastrointest endosc. 2012;75:467-73. 3. loperfido s, angelini g, benedetti g, et al. major early complications from diagnostic and therapeutic ercp: a prospective multicenter study. gastrointestinal endoscopy. 1998;48(1):1-10. 4. fatima j, baron th, topazian md, et al. pancreaticobiliary and duodenal perforations after periampullary endoscopic procedures: diagnosis and management. archives of surgery. 2007;142(5):448-55. 5. thorson cm, ruiz psp, roeder ra, sleeman d, casillas vj. the perforated duodenal diverticulum. archives of surgery. 2012;147(1):81-8. 6. smith g, year iii h, lieberman g. an atlas of complications of ercp. 7. ferrara f, luigiano c, billi p, jovine e, cinquantini f, d'imperio n. pneumothorax, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema after ercp. gastrointestinal endoscopy. 2009;69(7):1398-401. 8. preetha m, chung yfa, chan wh, et al. surgical management of endoscopic retrograde cholangiopancreatography‐related perforations. anz journal of surgery. 2003;73(12):1011-4. 9. kahaleh m, freeman m. prevention and management of postendoscopic retrograde cholangiopancreatography complications. clinical endoscopy. 2012;45(3):305-12. 10. howard tj, tan t, lehman ga, et al. classification and management of perforations complicating endoscopic sphincterotomy. surgery. 1999;126(4):658-65. 11. enns r, eloubeidi m, mergener k, et al. ercp-related perforations: risk factors and management. endoscopy. 2002;34(04):293-8. 12. silviera ml, seamon mj, porshinsky b, et al. complications related to endoscopic retrograde cholangiopancreatography: a comprehensive clinical review. j gastrointestin liver dis. 2009;18(1):73-82. archives of academic emergency medicine. 2019; 7 (1): e46 br i e f re p o rt atropine challenge test in screening the organophosphorus poisoning cases with atypical presentation; a brief report shahin shadnia1, nasim zamani1, sara nikpour2, ali saffaei3, mohammad reza farnia4∗ 1. department of clinical toxicology, loghman hakim hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. forensic medicine department, loghman hospital, shahid beheshti university of medical sciences, tehran. 3. student research committee, department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 4. emergency department, imam reza hospital, school of medicine, kermanshah university of medical sciences, kermanshah, iran. received: june 2019; accepted: july 2019; published online: 19 august 2019 abstract: introduction: atropine is not recommended in organophosphorus (ops) poisoning cases without any obvious clinical signs. this study aimed to evaluate the clinical utility of atropine challenge test in screening ops poisoning cases with atypical presentation. methods: in this prospective cross sectional study, after primary supportive care, patients with atypical pretentions of ops poisoning underwent atropine challenge test (1 mg intravenously) and demographic parameters, clinical presentations, and serum level of cholinesterase enzyme were compared between cases with positive and negative test results. results: 20 patients with the mean age of 47.60 ± 13.25 years were studied. the mean time since exposure and initial symptoms was 6.17 ± 2.99 hours. the most common clinical presentations were tachycardia (55%) and flushing (35%). the atropine challenge test was positive in 3 (15.00%) cases. the two groups were the same regarding gender distribution (p = 0.582), mean age (p = 0.957), clinical presentation (p > 0.05), and mean pr interval (p = 0.729). the level of cholinesterase was 220.00 ± 15.52 u/ml and 332.17 ± 143.99 u/ml in patients with positive and negative atropine challenge test, respectively (p = 0.006). conclusion: patients with positive atropine challenge test had a significantly lower level of serum cholinesterase and response to atropine in their therapeutic management. hence, atropine challenge test could be considered as a useful clinical test in the setting of acute ops poising. keywords: organophosphorus compounds; atropine; organophosphate poisoning; acetylcholine; toxicity cite this article as: shadnia sh, zamani n, nikpour s, saffaei a, farnia m r. atropine challenge test in screening the organophosphorus poisoning cases with atypical presentation; a brief report . arch acad emerg med. 2019; 7(1): e46. 1. introduction organophosphorus (ops) insecticides are used for agriculture, vector control, and domestic usages. despite the obvious benefits of these agents, acute ops poisoning is increasing worldwide (1, 2). because of their ease of accessibility, ops products are frequently used for self-poisoning intentions and it is an important public health issue in some developing countries (3, 4). ops products are the most important ∗corresponding author: mohammad reza farnia; emergency department, imam reza hospital, school of medicine, kermanshah university of medical sciences, kermanshah, iran. tel: 00988334276301, email: mr.farnia@kums.ac.ir source of toxicity and death globally and they cause more than 200,000 deaths every year in some developing countries (5, 6). acute ops poisoning can lead to acute cholinergic syndrome, seizures, muscle weakness, loss of consciousness, and respiratory arrest. ops through the inhibition of acetyl cholinesterase can stimulate both muscarinic, nicotinic, and adrenergic receptors (7). these effects may lead to the accumulation of acetylcholine. respiratory failure and cardiac arrest are the most usual causes of death in acute ops poisoning patients (8). patients with acute ops poisoning should undergo prompt evaluation and management of disorders in airway, breathing, and blood circulation. further interventions are based on risk assessment and clinical observations during regular monitoring (9). once clinithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. shadnia et al. 2 cal evaluations indicate the use of antidotes, they should be administered promptly. there are three most broadly used classes of antidotes, including muscarinic antagonists (for example: atropine), oximes (for example: pralidoxime and obidoxime), and benzodiazepines (10). atropine has no effect on the neuromuscular junction and muscle weakness, therefore oximes are administered to reverse neuromuscular blockage. atropine is not recommended in patients without any obvious clinical signs (11). however, in cases where the physicians doubt the diagnosis or cases with atypical presentation, atropine challenge test is recommended (12). the aim of this study was to evaluate the clinical utility of atropine challenge test in screening the ops poisoning cases with atypical presentation. 2. methods 2.1. study design and setting in this prospective cross sectional study, patients with ops poisoning who were referred to the emergency department of loghman hakim hospital, tehran, iran, between january 2017 and january 2018, were studied. this center is a national referral center for poisoning and toxicity in iran. this study was approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: 19663). 2.2. participants patients who were between 18 and 65 years old, were exposed to ops intentionally or accidentally, and had atypical presentation of ops poisoning (vague or alleviated signs of poisoning and unknown sources of poison) were included. patients who had received atropine before presenting to ed or had hepatic or renal failure were excluded. 2.3. data gathering age, gender, clinical signs and symptoms (tachycardia, mydriasis, flushing, agitation and dyspnea), pr interval on electrocardiogram (ecg) (lead ii and v1), time from exposure to presentation of initial symptoms, and level of serum cholinesterase were recorded for all patients. a toxicology fellowship was responsible for data gathering. 2.4. atropine challenge test after primary supportive care including cardiac monitoring, airway management, supplementary oxygen therapy, and fluid and electrolytes management, atropine challenge test was performed for all patients. first, basic heart rate of the patient was recorded. then, atropine at dose of 1 mg was intravenously (median cubital vein) administered and patient heart rate was monitored. if the heart rate increased more than 20% of its baseline or more than 30 beats per second, the test was considered positive. other anticholinergic symptable 1: clinical presentations of patients with acute ops poisoning parameter frequency (%) tachycardia 11 (55.0) mydriasis 5 (25.0) flushing 7 (35.0) anxiety and agitation 6 (30.0) dyspnea 1 (5.0) toms such as tachycardia, mydriasis, flushing, agitation and dyspnea were recorded. all patients with positive atropine challenge test received atropine as treatment. 2.5. statistical analysis data were imported into spss software version 23.0 (ibm, usa). findings are presented as mean ± standard deviation or frequency (%). for all the tests (t-test, chi-square), the significance level was considered as 0.05 and results were reported as mean ± standard division (sd) or frequency (%). 3. results 20 patients with the mean age of 47.60 ± 13.25 years were studied. the mean time since exposure and initial symptoms was 6.17 ± 2.99 hours. the most common clinical presentations were tachycardia (55%) and flushing (35%) (table 1). on admission, pr interval was 77.95 ± 7.21 milliseconds and mean level of serum cholinesterase was 315.35 ± 138.47 u/ml. atropine challenge test was positive in 3 (15.00%) cases. patients with negative atropine challenge test did not receive atropine, except one patient. table 2 compares the baseline characteristics of patients with positive and negative atropine challenge test. the two groups were the same regarding gender distribution (p = 0.582), mean age (p = 0.957), clinical presentation (p > 0.05), and mean pr interval (p = 0.729). the level of cholinesterase was 220.00 ± 15.52 u/ml and 332.17 ± 143.99 u/ml in patients with positive and negative atropine challenge test, respectively (p = 0.006). 4. discussion based on the findings of the present study, patients with positive atropine challenge test had a significantly lower level of serum cholinesterase and response to atropine in their therapeutic management. hence, atropine challenge test could be considered as a useful clinical test in the setting of acute ops poising. patients with acute ops poising must undergo prompt evaluation and management (13). clinical researches in asia have shown how atropine can prevent deaths in ops patients (14). however, the practitioners are still unsure regarding which cases are most likely to benefit from the use of atthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e46 table 2: comparing the baseline characteristics of patients with positive and negative atropine challenge test variables atropine challenge test p value positive negative age (years) mean ± sd 48.00 ± 12.12 47.53 ± 13.79 0.957 gender male 1 (5.0) 9 (45.0) 0.582 female 2 (10.0) 8 (40.0) pr interval (millisecond) mean ± sd 79.33 ± 4.16 77.71 ± 7.70 0.729 tachycardia yes 0 (0.0) 11 (55.0) 0.074 no 3 (15.0) 6 (30.0) mydriasis yes 0 (0.0) 5 (25.0) 0.399 no 3 (15.0) 12 (60.0) flushing yes 1 (5.0) 6 (30.0) 0.730 no 2 (10.0) 11 (55.0) anxiety and agitation yes 0 (0.0) 6 (30.0) 0.319 no 3 (15.0) 11 (55.0) dyspnea yes 0 (0.0) 1 (5.0) 0.850 no 3 (15.0) 16 (80.0) cholinesterase (u/ml) mean ± sd 220.00 ± 15.52 332.17 ± 143.99 0.006 data are presented as mean ± standard deviation (sd) or frequency (%). ropine (15). since management of these patients should be done promptly, decision making regarding atropine usage is an important issue. the results of the current study showed that atropine challenge test is a good predictor for necessity of atropine usage. if the patient referred to emergency department with atypical presentation of ops poising, the atropine challenge test can be performed. this way, the initial management strategy can be determined. this test was first introduced in case reports and based on our knowledge there is not any systematic study in this regard. in one study, which was done by cappato et al., the clinical applicability of atropine challenge test was evaluated in discriminating organic from autonomic involvement of sinus automaticity (16). they found that atropine test is not very helpful in discriminating between an organic and an autonomic involvement of sinus automaticity in patients with sinus bradycardia. another point about atropine challenge test was discussed by erdman et al. they previously noted that atropine challenge test has never been empirically tested and may not be very sensitive or specific (17). it seems that patients with positive atropine challenge test required atropine in their therapeutic management and those with negative atropine challenge test may not require atropine. hence, atropine challenge test may be considered as atropine requirement indicator, and it is recommended to evaluate every patient with atypical presentations of ops poisoning with atropine challenge test. 5. limitation the main limitation of current research was its small sample size, however this was due to low incidence of ops poisoning with atypical presentations. the advantage of current research was its novelty, which introduced atropine challenge test as a crucial diagnostic test. 6. conclusion patients with positive atropine challenge test had a significantly lower level of serum cholinesterase and response to atropine in their therapeutic management. hence, atropine challenge test could be considered as a useful clinical test in the setting of acute ops poising. 7. appendix 7.1. acknowledgements the authors wish to thank staff members who helped them perform this research. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. shadnia et al. 4 7.2. author contribution shahin shadnia, nasim zamani, and mohammad reza farnia designed the study. mohammad reza farnia and sara nikpour participated in acquisition of data. ali saffaei analyzed the data. sara nikpour participated in management of data. shahin shadnia, nasim zamani, sara nikpour, mohammad reza farnia, and ali saffaei wrote the first draft and others revised the manuscript critically. all authors approved of the final version of the manuscript to be published and are accountable for all aspects of the work. authors orcids shahin shadnia: 0000-0002-9401-0781 nasim zamani: 0000-0002-2091-0197 sara nikpour: 0000-0003-1986-3992 ali saffaei: 0000-0002-9563-924x mohammad reza farnia: 0000-0002-4397-8661 7.3. funding/support this study was supported by shahid beheshti university of medical sciences. 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. soltaninejad k, shadnia s. history of the use and epidemiology of organophosphorus poisoning. basic and clinical toxicology of organophosphorus compounds: springer; 2014. p. 25-43. 2. eddleston m, buckley na, eyer p, dawson ah. management of acute organophosphorus pesticide poisoning. the lancet. 2008;371(9612):597-607. 3. hung d-z, yang h-j, li y-f, lin c-l, chang s-y, sung fc, et al. the long-term effects of organophosphates poisoning as a risk factor of cvds: a nationwide populationbased cohort study. plos one. 2015;10(9):e0137632. 4. gunnell d, eddleston m, phillips mr, konradsen f. the global distribution of fatal pesticide self-poisoning: systematic review. bmc public health. 2007;7(1):357. 5. eddleston m, phillips mr. self poisoning with pesticides. bmj. 2004;328(7430):42-4. 6. eddleston m. patterns and problems of deliberate self-poisoning in the developing world. qjm. 2000;93(11):715-31. 7. shadnia s, ashrafivand s, mostafalou s, abdollahi m. n-acetylcysteine a novel treatment for acute human organophosphate poisoning. int j pharmacol. 2011;7(6):732-5. 8. aghabiklooei a, mostafazadeh b, farzaneh e, morteza a. does organophosphate poisoning cause cardiac injury? pakistan journal of pharmaceutical sciences. 2013;26(6). 9. shadnia s, okazi a, akhlaghi n, sasanian g, abdollahi m. prognostic value of long qt interval in acute and severe organophosphate poisoning. journal of medical toxicology. 2009;5(4):196. 10. pajoumand a, shadnia s, rezaie a, abdi m, abdollahi m. benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides. human & experimental toxicology. 2004;23(12):565-9. 11. paudyal bp. organophosphorus poisoning. jnma; journal of the nepal medical association. 2008;47(172):251-8. 12. isha it, alam zn, shaha bk, bari ms, bari mzj, chowdhury fr. paraquat induced acute kidney injury and lung fibrosis: a case report from bangladesh. bmc research notes. 2018;11(1):344. 13. eddleston m, dawson a, karalliedde l, dissanayake w, hittarage a, azher s, et al. early management after self-poisoning with an organophosphorus or carbamate pesticide–a treatment protocol for junior doctors. critical care. 2004;8(6):r391. 14. eddleston m, eyer p, worek f, juszczak e, alder n, mohamed f, et al. pralidoxime in acute organophosphorus insecticide poisoning–a randomised controlled trial. plos medicine. 2009;6(6):e1000104. 15. kumar sv, fareedullah m, sudhakar y, venkateswarlu b, kumar ea. current review on organophosphorus poisoning. arch appl sci res. 2010;2(4):199-215. 16. cappato r, alboni p, paparella n, toselli t, candini gc, tomasi am. bedside evaluation of sinus bradycardia: usefulness of atropine test in discriminating organic from autonomic involvement of sinus automaticity. american heart journal. 1987;114(6):1384-8. 17. heide e. cholinesterase inhibitors: including insecticides and chemical warfare nerve agents part 5: the intermediate syndrome. 2012th. agency for toxic substances and disease registry (atsdr), avalable at: http://www.atsdr.cdc.gov/csem/csem.asp. 2012. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e49 or i g i n a l re s e a rc h diagnostic accuracy of ultrasonography in diagnosis of metatarsal bone fracture; a cross sectional study mohsen ebrahimi1, seyed reza habibzadeh1, sayyed reza ahmadi1, samaneh khajeh nasiri2, mohammad majid kaveh1, mahdi foroughian1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. department of radiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: may 2019; accepted: july 2019; published online: 17 august 2019 abstract: introduction: metatarsus is one of the most common sites in the sole of foot bones fractures. the aim of this study was to determine the diagnostic accuracy of ultrasound in diagnosis of metatarsal bone fractures following foot trauma. methods: this cross-sectional study was carried out on patients with blunt foot trauma admitted to emergency department of a hospital in mashhad, iran from january to september 2016. all patients were evaluated with bedside ultrasound for the presence of first to fifth metatarsal fractures and screening performance characteristics of ultrasonography in detection of metatarsal fractures were calculated considering foot radiography as the reference test. results: the study was conducted on 102 patients with a mean age of 35.14±14.32 years (56.8% male). the most common signs of trauma in physical examination were pain and tenderness (100%), swelling (96.1%), ecchymosis (14.7%) and deformity (1.9%). sensitivity, specificity, and positive and negative likelihood ratio of ultrasonography in detection of metatarsal bone fracture were 96.7% (95% ci: 0.83-0.99), 84.5% (95% ci: 0.73-0.92), 73.1% (95% ci: 0.57-0.85), and 98.3% (95% ci: 0.91-0.99), respectively. the overall accuracy of ultrasonography was 0.906 (95% ci: 0.844 – 0.969) based on area under the receiver operating characteristic (roc) curve. conclusion: considering the excellent diagnostic accuracy, ultrasonography can be used as an alternative means in diagnosis of metatarsal bone fractures. keywords: ultrasonography; radiography; fractures, bone; metatarsal bones cite this article as: ebrahimi m, habibzadeh s r, ahmadi s r, khajeh nasiri s, kaveh m m, foroughian m. diagnostic accuracy of ultrasonography in diagnosis of metatarsal bone fracture; a cross sectional study. arch acad emerg med. 2019; 7(1): e49. 1. introduction foot and ankle are areas of the body that are most commonly exposed to trauma (1, 2). foot injuries account for about 25% of musculoskeletal injuries leading to emergency department visits (3). although such injuries usually are not considered life threatening, but the function of involved organs could be at risk. therefore, correct and rapid diagnosis of these injuries as well as early treatment can prevent longterm and short-term complications (4, 5). on the other hand, it should be noted that accurate diagnosis of injuries to the foot bones, particularly metatarsal injuries, is not possible with physical examination alone and imaging procedures always have got a foothold, at least to rule out metatarsal frac∗corresponding author: mahdi foroughian; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: 05138525312, email: foroughianmh@mums.ac.ir tures, as one of the most important clinical decisions (6, 7). over time, the use of ultrasound (us) imaging has grown due to its low cost and lack of harmful radiation and good capability to check the soft tissue and its importance in diagnosis of foot and ankle injuries has increased (8). some studies have evaluated the use of ultrasound in emergency departments for assessing the existence of foreign bodies (9) as well as examining the skeletal structures in many rheumatic diseases (10). since us is considered as a method of dynamic measurements, it accurately detects the smallest changes in the anatomical structure of body and is very useful in patients with no specific clinical symptoms (3, 6, 11). to date, foot and ankle trauma is one of the most common indications in ultrasound assessment. in addition, patients usually cooperate for ultrasound (8, 12). on the other hand, because the same physician who examined the patient performs the ultrasound, it also provides more rapid diagnosis; since the doctor can easily match up findings of history taking with imaging and reach the best diagnosis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ebrahimi et al. 2 in studies that have been conducted recently, the accuracy of the us in diagnosis of foot and ankle injuries has been reported as very good and the results have increased willingness to do further investigations (3, 5, 6, 9, 13). however, these small studies have indicated that the use of us could be helpful as much as plain radiography in diagnosis of metatarsal fractures. based on above-mentioned points, the aim of this study was to determine the diagnostic value of ultrasound in diagnosis of metatarsal bone fracture in patients referring to the emergency department due to foot and ankle blunt trauma. 2. methods 2.1. study design and setting this cross-sectional study was carried out on patients admitted to emergency department of edalatian hospital, mashhad, iran, from january to september 2016, following foot trauma. all patients underwent ultrasonography and radiography of foot and diagnostic accuracy of ultrasonography in detection of metatarsal bone fractures was measured. this study was approved by the ethics committee of mashhad university of medical sciences, iran (code: 931645). in addition, all items expressed in the declaration of helsinki were taken into account. the patients filled the written consent form for enrollment in the study. given that our study was an observational one, there was no threat to patients for therapeutic research efforts; however, the researchers supported all patients during the study in case of any complication. 2.2. participants all conscious cases over 16 years old with stable hemodynamics and clinical indication for foot radiographic examination were enrolled to the study. lack of patient consent, penetrating trauma, open fracture or dislocation, and the presence of osteomyelitis or chronic skeletal problems were among the exclusion criteria. 2.3. data gathering basic information, including age, gender and type of trauma (penetrating or blunt) was recorded for patients. then, the emergency medicine specialist performed bedside ultrasound for all patients and ultrasonography findings regarding presence or absence of metatarsal bone fractures were recorded. then, all patients underwent foot radiography (posterior-anterior and oblique views). the emergency medicine specialist, faculty member with board certificate, interpreted radiographic findings. in addition, a radiologist as a project colleague interpreted all radiographs. the radiographic findings were recorded as the presence or absence of fractures. the emergency medicine specialist was unaware of radiographic findings when doing the ultrasound and the radiologist was also blind to the sonographic findings. the emergency medicine resident was responsible for data gathering. in this study, the samples were selected by nonrandom purposive sampling method. all sonographies were performed according to ankle ultrasound technical guidelines of european society of musculoskeletal radiology, using ultrasound device (manufactured by honda-japan) and 10 mhz linear probe. in addition, the bone structures that should have been evaluated by ultrasound were prepared in a checklist in advance for specialists to assess the items based on the checklist. the bone checklist included first to fifth metatarsals. the fracture diagnosis criteria in ultrasound were the presence of cortical disruption or stepping or axial deviation of the bone surface. 2.4. statistical analysis given the 60% prevalence of metatarsal bone fractures and 87.3% sensitivity reported in the study by atilla in 2014 (13), as well as taking into account the type i error of 0.05, l=0.06, the sample size was calculated as 72. considering a 20% dropout rate, the final sample size was 90 patients. all data obtained from the patients were entered into the computer and statistically analyzed using spss 17.0 for windows (ssps inc., chicago, il, usa). given the normal distribution of data, quantitative data were expressed as mean and standard deviation. the sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr), and negative likelihood ratio (nlr) of sonography in detection of metatarsal bone fractures were calculated with 95% confidence interval (ci) using the medcalc version 16.1 software. p<0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of participants the study was conducted on 102 patients with a mean age of 35.14±14.32 years (56.8% male). the trauma had happened during everyday life in 63 (61.8%) patients, due to accident in 27 (26.5%) patients, and during exercise in 12 (11.8%) patients. the most common signs of trauma in physical examination were pain and tenderness (100%), swelling (96.1%), ecchymosis (14.7%) and deformity (1.9%). the mentioned signs were frequently detected in fore-foot (> 70%). 3.2. diagnostic measures the prevalence of metatarsal fracture was 30.3% (n=31) based on radiographic findings and 40.1% (n=41) according to sonographic results. overall, the ultrasound did not detect the fracture for one patient (medial side of the fifth metatarsal). in addition; 11 (27%) suspected fractures on ultrasonography were not confirmed by radiography. the sensitivity, specificity, ppv, npv, plr, and nlr of ultrasonograthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e49 figure 1: area under the receiver operating characteristic (roc) curve of ultrasonography in detection of metatarsal bone fracture. phy in detection of metatarsal bone fracture were 96.7% (95% ci: 0.83-0.99), 84.5% (95% ci: 0.73-0.92), 73.1% (95% ci: 0.570.85), 98.3% (95% ci: 0.91-0.99), 6.25 (95%ci: 3.61-10.79), and 0.04 (95%ci: 0.01-0.26), respectively. the overall accuracy of ultrasonography based on area under the receiver operating characteristic (roc) curve was 0.906 (95% ci: 0.844 – 0.969, figure 1). 4. discussion the results showed that ultrasound has remarkable sensitivity and specificity compared to radiography and can be used in a shorter time than radiography in emergency situations for diagnosis of metatarsal bone fractures. the use of ultrasound for diagnosis of fractures by emergency physicians is more important when the priority is deciding within the shortest possible time, especially when the radiography ward is overcrowded and there is the need to speed up the triage of patients to properly manage the emergency department. in addition, sometimes a doctor has high clinical suspicion to the existence of concurrent soft tissue damages in patients admitted to the emergency department. in these cases, due to higher power of ultrasound in diagnosis of soft tissue injuries compared to radiography, using ultrasound can be a priority in diagnosis. in order to use ultrasound in diagnosis of fractures in the emergency department, knowing the diagnostic power of ultrasound for observing the fractures is important. this issue is something that very few studies have examined as many articles related to the use of ultrasound in diagnosis of metatarsal fractures are case reports (4-8, 11, 12). preliminary results of this study confirmed that ultrasound was a powerful tool in triage of patients referring to the emergency department with suspected metatarsal bone fracture; this result is consistent with two other studies in this regard. in a study by ekinci et al. (14) sensitivity, specificity, positive predictive value and negative predictive value of ultrasound in diagnosis of metatarsal fractures were reported as 100%, 99.1%, 95.2% and 100%, respectively. in a study by canagasabey et al. (2) sensitivity, specificity, positive predictive value and negative predictive value of ultrasound in diagnosis of fractures were found to be 90.9%, 90.9%, 52.5% and 98.9%, respectively. the sensitivity was over 90% and specificity was over 85% in both studies, similar to our research. high sensitivity and specificity are two important features in determining the power of a diagnostic tool; hence, ultrasound seems to be a powerful tool in diagnosis of fractures. ppv was reported as 73% and npv was 100% with upward approximation. high negative predictive value of ultrasound may be the most important parameter confirming the diagnostic value of ultrasound; because if ultrasound is negative, the presence of fracture can be ruled out, leading to better triage of the patients. however, since ppv and npv are related to incidence rate of the disease in the study population and fracture prevalence rates are different among various studies, likelihood ratio, which is not under influence of disease prevalence, is used for comparison. in the present study, plr and nlr were reported as 6.25 and 0.04, respectively, indicating the high diagnostic value of ultrasonography. it seems that the high diagnostic value of ultrasound in diagnosis of metatarsal fractures can be attributed to the dynamics of ultrasonography and the ability of the operator to create images in different sections. it should be noted that the reason for slight differences between the results of the current and other studies regarding sensitivity, specificity and other parameters of diagnostic power could be due to differences in sample size, different quality of ultrasound devices used, experience and academic ability of ultrasound operators. importantly, about 4% of patients in our study were pregnant, which highlights the importance of using x-rayindependent methods to diagnose fractures. moreover, since the physician responsible for the ultrasound can press the probe when performing ultrasound examination, fractures with bone dynamic movements are more easily detected during ultrasound, and the pressure mentioned in previous studies will not be accompanied with unbearable pain for patients (3). the gold standard for assessment of fracture in this study was radiographic findings interpreted by the radiologist. this crithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ebrahimi et al. 4 terion was chosen because plain radiography is performed in almost all patients with suspected fractured foot trauma. selection of ct scan as the standard criterion would impose excessive and sometimes unnecessary radiation on the patients and mri was associated with high and unnecessary time and cost. 5. conclusion according to the results of the present study, ultrasound has high sensitivity, high specificity, negative predictive value of about 100%, and favorable likelihood ratios in diagnosis of metatarsal fractures. therefore, it seems that use of ultrasound can serve as a very good alternative to radiography in diagnosis of metatarsal fractures. 6. appendix 6.1. acknowledgements none. 6.2. author contribution ebrahimi, habibzadeh, nasiri, foroughian study conception and design: ebrahimi, habibzadeh acquisition of data: kaveh analysis and interpretation of data: ahmadi, foroughian drafting of manuscript: nasiri critical revision: foroughian authors orcids mohsen ebrahimi: 0000-0003-2168-8476 seyed reza habibzadeh: 0000-0003-4569-1776 sayyed reza ahmadi: 0000-0003-4921-976x samaneh khajeh nasiri: 0000-0002-8228-6633 mahdi foroughian: 0000-0002-3944-9361 6.3. funding/support the study was financially supported by mashhad university of medical sciences. 6.4. conflict of interest the authors do not have any conflict of interest to declare. references 1. english e. fractures and soft tissue injuries of the feet and ankle. canadian family 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and sonographic synovitis in patients with painful knee osteoarthritis. international journal of rheumatic diseases. 2017 may;20(5):561-6. pubmed pmid: 26915050. epub 2016/02/26. eng. 11. battaglia pj, kaeser ma, kettner nw. diagnosis and serial sonography of a proximal fifth metatarsal stress fracture. journal of chiropractic medicine. 2013 2013/09/01/;12(3):196-200. 12. roehrig gj, mcfarland eg, cosgarea aj, martire jr, farmer kw. unusual stress fracture of the fifth metatarsal in a basketball player. clinical journal of sport medicine. 2001;11(4). 13. atilla od, yesilaras m, kilic ty, tur fc, reisoglu a, sever m, et al. the accuracy of bedside ultrasonography as a diagnostic tool for fractures in the ankle and foot. academic emergency medicine : official journal of the society for academic emergency medicine. 2014 sep;21(9):1058-61. pubmed pmid: 25269589. epub 2014/10/02. eng. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e49 14. ekinci s, polat o, gunalp m, demirkan a, koca a. the accuracy of ultrasound evaluation in foot and ankle trauma. the american journal of emergency medicine. 2013 2013/11/01/;31(11):1551-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 85 emergency (2014); 2 (2): 85-89 original research oral chloral hydrate compare with rectal thiopental in pediatric procedural sedation and analgesia; a randomized clinical trial reza azizkhani1, soheila kanani1*, ali sharifi2, keihan golshani1, babak masoumi1, omid ahmadi1 1. department of emergency medicine, isfahan university of medical sciences, isfahan, iran 2. department of general surgery, isfahan university of medical sciences, isfahan, iran abstract introduction: the increasing use of diagnostic imaging in pediatric medicine has resulted in growing need for procedural sedation and analgesia (psa) to minimize motion artifacts during procedures. the drug of choice in pediatric psa was not introduced until now. the aim of the present study was comparison of oral chloral hydrate (och) and rectal sodium thiopental (rst) in pediatric psa. methods: in the present randomized clinical trial, 2-6 years old pediatrics who referred for performing brain computed tomography scan was enrolled and were randomly divided in to two groups. och (50mg/kg) and rst (25mg/kg) were prescribed and a trained nurse recorded the time from drug prescription to receiving the conscious sedation (onset of action), the total period which the patient has the ramsay score≥4 (duration of action), and adverse effect of agents. mann-whitney u test and chi-squared test, and non-parametric analysis of covariance (ancova) were used for comparisons. results: one hundred and forty children were entered to two groups of och and rst, randomly. the patients of two groups had similar age, sex, weight, and baseline vital signs except for diastolic blood pressure (p<0.001). the onset of action in och and rst groups were 24.5±6.1and 28.7±5.2 minutes, respectively (p<0.001). duration of action in och and rst groups were 12.9±2.8 minutes and 13.7±2.6 minutes, respectively (p=0.085). non-parametric ancova revealed that only diastolic blood pressure was affected by drug prescription (p=0.001). in 11(15.7%) patients in rst group, diarrhea was observed during 24 hours (p=0.001). oxygen desaturation was observed only in two patients, both in och group. conclusion: each of the sedative has advantages and disadvantages that should be considered when selecting one for inducing short-term sedation. it seems that rectal sodium thiopental and oral chloral hydrate are equally effective in pediatric psa and based on patient’s condition we can administrate one of these agents. key words: pediatrics; conscious sedation; anesthesia and analgesia; chloral hydrate; thiopental cite this article as: azizkhani r, kanani s, sharifi a, golshahi k, masoumi b, ahmadi o. oral chloral hydrate compare with rectal thiopental in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;2(2):85-9. introduction:1 he increasing use of diagnostic imaging in pediatric medicine has resulted in growing need for procedural sedation and analgesia (psa) to minimize motion artifacts during procedures. the drug of choice in pediatric psa was not introduced until now. the prescription of most sedative drugs like pentobarbital requires intravenous (iv) route of administration, undesirable for the child and parents (1). oral chloral hydrate (och) is one of the sedative agents, which it is independency from venipuncture turns it to be a considerable alternative for pediatric psa (2-6). this drug are widely used in pediatric sedation. och is used for sedation of children under 6 years old. it is a non *corresponding author: soheila kanani; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989136470851; fax:+983117923445; email: soheilakanani@gmail.com received: 1 april 2014; accepted: 5 april 2014 opiate, non-benzodiazepines, and oral hypnotic drug. most studies showed that it can be considered as a safe and more effective drug for short-term sedation (7-10) with successful rates of 85%–98% (2, 11). but, it has unpleasant taste and some studies showed that it could be carcinogen (12). another alternative drug is rectal sodium thiopental (rst). for the first time in 1979, rectal route of administration was used for psa during computed tomography (ct) scan and favorable results achieved. several studies revealed that rectal sodium thiopental (rst) has an effective role in children's sedation. this drug well absorbed from distal rectum and its effect appears within 5-10 minutes (1, 13-16). akhlaghpour and his colleagues showed 98% successful rate of rst in pediatric psa (17). if the children don’t suffer from porphyria, diarrhea, breathing problems, active infection, severe cardiovascular disease, and asthma the drug with dose of 25mg/kg is prescribed rectally t mailto:soheilakanani@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com azizkhani et al 86 through nelaton catheter (18).there are a few study regarding the comparison of advantages and disadvantages of above mentioned drugs in pediatric psa. the aim of the present study was comparison of och and rst in pediatric psa. methods: study design and setting: the present randomized clinical trial was prepared based on helsinki declaration and approved by ethics committee of isfahan university of medical sciences. in addition, the study was registered in iranian registry of clinical trial. after explanation of sedation protocol, the consent form was obtained from the parents. participants in this project, study population were 2-6 years old pediatrics who referred for performing brain computed tomography scan to alzahra and kashani esfehani hospitals, esfehan, iran, during 2012. they were randomly divided in to two groups of och and rst, based on block randomization method. the children with following criteria were excluded from the study: intracranial hypertension, seizure, airway problems like hypertrophie adenoid, ileus or suspected of having intestinal obstruction, liver and kidney disease, sensitivity to barbiturates, porphyria, diarrhea, active infection, cardiovascular disease, asthma, and drug sensitivity. intervention at first, patient’s information was collected and recorded to the computerized database by a radiology nursing staff. the database contains information about demographic, clinical and sedation data such as total time of sedation, onset of action, duration of action, and complications. they were randomly divided in to two groups of och and rst using randomized permuted block design. in och group, 50mg/kg of chloral hydrate was drawn in a syringe and administered orally. the consumption box of chloral hydrate was purchased from merck kgaa company, germany. following drug prescription the sedation score of the patient was evaluated and if it was equal to ramsay score of four, the child underwent ct scan along with an equipped resuscitation team and continuous pulse oximetry. after 15 minutes if the level of sedation decreased to score<4, another 50mg/kg dose of the drug was prescribed. in the case of decreased oxygen saturation, 100% oxygen delivered using nasal cannula or oxygen mask. in rst group, like the previous group, 25mg/kg of sodium thiopental, diluted to total volume of 10 milliliter with distilled water, was injected through nelaton catheter, entered five centimeter to the rectum. in this project, the dose of 25mg/kg was used, which is the least effective dose in most of studies (9, 17). if the patient achieved ramsey score of four, underwent ct scan with similar condition of previous group. if there was, no sedation observed after 15 minutes, 15mg/kg of thiopental sodium like the first time was delivered rectally. the consumed vial was provided from rote media company, germany. in both groups, all of the patients underwent continuous pulse oximetry and close monitoring by an emergency medicine resident during and after the time of procedure until full awakening. outcome: outcome parameters recorded by the nursing included the time from drug prescription to receiving the conscious sedation (onset of action), and the total period which the patient has the ramsay score≥4 (duration of action). the adverse recorded events included failed sedation, oxygen desaturation (≥ 4% decrease in oxygen saturation), increasing the frequency of defecation during the first 24 hours of drug administration, based on parent's report (diarrhea), and delayed events such as vomiting, hyperactivity, irritability, or other symptoms that caused parental concerns. after full awaking and before discharging the children, warning signs of possible side effects was trained to the parents and contacted them after 24 hours to find and register the side effects concluded breathing problems, diarrhea, and increasing the child activity. definitions: conscious sedation: in terms of ramsay sedation scale (19) is the condition that the patient is asleep and response to stimulations slowly (score four). hypotension in 1-10 years old children: systolic blood pressure <70 mmhg + (2×age in years) statistical analysis statistical analysis was performed using a statistical software package (spss version 20; chicago, il). mannwhitney u test and chi-squared test were performed for quantitative and qualitative variables, respectively. in addition, non-parametric analysis of covariance was used for comparison of post procedure’s vital signs including respiratory rate (rr); oxygen saturation (o2sat); systolic blood pressure (sbp); and diastolic blood pressure (dbp) between och and rst groups. p <0.05 was taken to indicate statistical significance. results: one hundred and forty children were entered to two groups of och and rst, randomly. the patients of two groups had similar age, sex, weight, and baseline vital signs except for diastolic blood pressure (p<0.001) (table1). in och and rst groups, 58 (82.9%) and 61 (51.26) patients reached ramsay score of four, respectively (p=0.49). rescue doses are administered for 12(17.1%) patients in och group and 9 (12.9%) in rst group. finally, all these patients reached to ramsay score of four. the onset of action in och and rst groups were 24.5±6.1and 28.7±5.2 minutes, respectively (p<0.001). duration of action in och and rst groups were 12.9±2.8 minutes and 13.7±2.6 minutes, respectively (p=0.085) (figure 1). table 2 shows the compari this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 87 emergency (2014); 2 (2): 85-89 son of vital signs after the sedation in two groups. nonparametric ancova revealed that only diastolic blood pressure was affected by drug prescription (p=0.001). mean diastolic blood pressure after administration of och and rst was 60.4±6.95 and 53.9±6.9, respectively. in 11(15.7%) patients in rst group, diarrhea was observed during 24 hours (p=0.001). oxygen desaturation was observed only in two patients, both in och group. any other side effects were not seen during and after 24 hours of the sedation in two groups. discussion: the increasing use of computed tomography, magnetic resonance imaging (mri), and interventional radiology has resulted in a growing number of infants who require sedation while undergoing imaging procedures. in this study the clinical safety, effectiveness, and potential side effects of och and rst in pediatric psa were compared. this project found no significant difference between the safeties of the two agents. adverse events occurred infrequently in both groups. most of patients were sedated with the first dose of sedative agents and only 21 patients included 17.1% in och and 12.9% in rst groups needed rescue dose. in the present trial onset of action was significantly longer in rst compared with och group, 28.7±5.2 versus 24.5±6.1 minutes, respectively. there was not seen any significant difference regarding duration of action between two groups. no sedation failure has been seen among them. most side effects related to diarrhea, were generally minimal and easily treated. glasier et al. stated that rts is a safe and effective agent for sedation of infants and children with a 96% successful rate (1). efficacy and safety of och and rst were compared in some studies. in a recent study granados et al. demonstrated a 97% successful rate of rst in pediatric psa and declared diarrhea (12.6%) as the most prevalent side effect (20). the mean duration of action for rst was 8.04 minutes in akhlaghpoor et al. study, which is five minutes less than our result (17). for decades, och has been widely used for short-term sedation of children (11, 21, 22). the acute toxicity of och is low in recommended single doses. however, acute overdoses may cause cardiorespiratory depression (23, 24). in the present study, we observed 2.9% of och treated patient suffered from desaturation, which is slightly higher than other studies. in a most recent study, finnemore et al. revealed that using och let to desaturation in 0.7% of neonates undergo mri (25). litman et al. showed 2.2 % preterm and term infants afflicted desaturation following och administration (26). overall, desaturation was the most side effect of och like the present study. in co mparison between och and rst, because of serious side effect of och, it seems that rst is better than och. although, 15.7% of rst cases suffered table 1: baseline characteristics of the study groups  characteristics chloral hydrate sodium thiopental p* age (year) 3.8±1.6 3.5±1.5 0.31 gender (%) male 45 (51.1) 43 (48.9) 0.73 female 25(48.1) 27(51.9) weight (kg) 14.54±4.33 15.80±4.44 0.11 rr (per minute) 16.4±2.1 15.9±1.4 0.30 (%) sat 2o 93.9±1.0 93.5±1.3 0.09 pr (per minute) 96.6±5.4 98.3±4.9 0.14 sbp (mmhg) 101.7±7.3 103.4±7.7 0.07 dbp (mmhg) 61.7±6.7 56.5±7.0 <0.001 *all p values derived from mann-whitney u test except gender (chi-squared test). rr: respiratory rate; o2 sat: oxygen saturation; pr: pulse rate; sbp: systolic blood pressure; dbp: diastolic blood pressure table 2: vital signs before and after sedation in the study groups  parameters chloral hydrate sodium thiopental p* rr (per minute) 20.3±1.8 19.7±2.3 0.25 (%) sat 2o 91.6±1.1 91.2±1.4 0.17 pr (per minute) 109.8±6.95 108.4±7.5 0.12 sbp (mmhg) 101.4±7.3 103.9±7.7 0.16 dbp (mmhg) 60.4±6.95 53.9±6.9 0.001 *all p values derived from non-parametric ancova adjusted for pre-treatment level of variable except pulse rate (mann-whitney u test). rr: respiratory rate; o2sat: oxygen saturation; pr: pulse rate; sbp: systolic blood pressure; dbp: diastolic blood pressure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com azizkhani et al 88 from mild diarrhea and only 2.9 och treated patients experienced the oxygen desaturation, the och side effect may be hazardous. in addition, the mild rectal irritation and diarrhea related apparently to rectal administration, generally acceptable for parents and physicians. it was consistent with rooks et al. study, implied the better safety and effectiveness of pentobarbital (is a short-acting barbiturate like rst) than och (27). however, rst has some limitation for instance; it should be avoided in patients with known or suspected rectal trauma or severe thrombocytopenia. infants younger than three months were not sedated with rectal thiopental because they tend to expel the drug from the rectum. in total rst is more favorable than oct in our study due to the ease of administration, rapid onset of action, safety, and better compliance. limitations: the limitations of this study were its small sample size and short duration of follow up. therefore, it is suggested that further studies be conducted with larger sample size, longer follow up periods and different dosages of oct and rst. conclusion: each of the sedative has advantages and disadvantages that should be considered when selecting one for inducing short-term sedation. it seems that rectal sodium thiopental and oral chloral hydrate are equally effective in pediatric psa and based on patient’s condition we can administrate one of these agents. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of alzahra and kashani esfehani hospitals in isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. glasier cm, stark je, brown r, james ca, allison jw. rectal thiopental sodium for sedation of pediatric patients undergoing mr and other imaging studies. ame j neuroradiol. 1995;16(1):111-4. 2. napoli kl, ingall cg, martin gr. safety and efficacy of chloral hydrate sedation in children undergoing echocardiography. j pediatr. 1996;129(2):287-91. 3. vade a, sukhani r, dolenga m, habisohn-schuck c. chloral hydrate sedation of children undergoing ct and mr imaging: safety as judged by american academy of pediatrics guidelines. am j roentgenol. 1995;165(4):905-9. 4. ronchera-oms cl, casillas c, marti-bonmati l, et al. oral chloral hydrate provides effective and safe sedation in paediatric magnetic resonance imaging. j clin pharm ther. 1994;19 (4):239-43. 5. greenberg sb, faerber en, aspinall cl, adams rc. highdose chloral hydrate sedation for children undergoing mr imaging: safety and efficacy in relation to age. am j roentgenol. 1993;161(3):639-41. 6. hubbard am, markowitz ri, kimmel b, kroger m, bartko mb. sedation for pediatric patients undergoing ct and mri. j comput assist tomogr. 1992;16(1):3-6. 7. da costa lr, da costa ps, lima ar. a randomized doubleblinded trial of chloral hydrate with or without hydroxyzine versus placebo for pediatric dental sedation. 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sedation for pediatric ophthalmic procedures: a retrospective review. j pediatr ophthalmol strabismus. 2014: 1-6. 23. nordt sp, rangan c, hardmaslani m, clark rf, wendler c, valente m. pediatric chloral hydrate poisonings and death following outpatient procedural sedation. j med toxicol. 2014:1-4. 24. sandberg kl, poole sd, sundell hw. cardio-respiratory response to moderate chloral hydrate sedation in young lambs. acta paediatr. 2013;102(4):391-6. 25. finnemore a, toulmin h, merchant n, et al. chloral hydrate sedation for magnetic resonance imaging in newborn infants. pediatr anesth. 2014;24(2):190-5. 26. litman rs, soin k, salam a. chloral hydrate sedation in term and preterm infants: an analysis of efficacy and complications. anesth analg. 2010;110(3):739-46. 27. rooks vj, chung t, connor l, et al. comparison of oral pentobarbital sodium (nembutal) and oral chloral hydrate for sedation of infants during radiologic imaging: preliminary results. am j roentgenol. 2003;180(4):1125-8. archives of academic emergency medicine. 2019; 7 (1): e52 rev i ew art i c l e outcomes of crowding in emergency departments; a systematic review hamid reza rasouli1, ali aliakbar esfahani2, mohammad nobakht2, mohsen eskandari2, sardollah mahmoodi1, hassan goodarzi1, mohsen abbasi farajzadeh2∗ 1. trauma research center, baqiyatallah university of medical sciences, tehran, iran. 2. marine medicine research center, baqiyatallah university of medical sciences, tehran, iran. received: june 2019; accepted: july 2019; published online: 28 august 2019 abstract: introduction: emergency department (ed) crowding is a global public health phenomenon affecting access and quality of care. in this study, we seek to conduct a systematic review concerning the challenges and outcomes of ed crowding. methods: this systematic review utilized original research articles published from 1st january 2007, to 1st january 2019. relevant articles from the pubmed (medline), embase, and google scholar databases were extracted using predesigned keywords. following the prisma guidelines, two reviewers independently evaluated the quality of the studies using critical appraisal skills programme for cohort studies and qualitative studies, and joanna briggs institute meta-analysis of statistics assessment and review instrument for studies. results: out of the total of 73 articles in the final record, we excluded 15 of them because of poor quality. this systematic review synthesized the reports of 58 original articles. the outcomes of multiple individual patients and healthcare-related challenges are comprehensively assessed. conclusions: ed crowding affects individual patients, healthcare systems and communities at large. the negative influences of crowding on healthcare service delivery result in delayed service delivery, poor quality care, and inefficiency; all negatively affecting the emergency patients’ healthcare outcomes, in turn. keywords: crowding; outcome assessment; emergency service, hospital; systematic review cite this article as: rasouli h r, aliakbar esfahani a, nobakht m, eskandari m, mahmoodi s, goodarzi h, abbasi farajzadeh m. outcomes of crowding in emergency departments; a systematic review. arch acad emerg mede. 2019; 7(1): e52. 1. introduction the requirement of emergency healthcare service is an ongoing issue (1). the emergency department (ed) is expected not only to provide emergency care to patients but also to fulfill the needs of the providers, and the communities at large. besides, the emergency department might be the only source of healthcare services to people especially in rural communities (1, 2). evidence shows an increase in emergency healthcare service utilization because of the increased rates of accidental injuries. however, the capacity of the emergency healthcare systems has not been well developed to respond to such high demand because creating a balance between emergency services and the required resources is challenging, especially ∗corresponding author: mohsen abbasi farajzadeh; marine medicine research center, baqiyatallah university of medical sciences, tehran, iran. tel: +9888053766, e-mail: mohsen10_fam@yahoo.com in under-resourced countries (3-5). this condition leads to crowding of the eds, which in turn impose public health challenges related to quality of healthcare and outcomes. crowding is a situation when an identified need for emergency healthcare services exceeds the available resources to provide emergency care to patients within an appropriate time frame (1, 3, 6). crowding of the ed leads to adverse outcomes for the patients, providers, the healthcare system and the community. delay in service provision to patients not only can compromise the quality of the emergency services but can also worsen their consequences. crowding of the ed might also lead to the violations of the norms and the service provision standards, which in turn might result in patients leaving the facilities without getting the required services. thus, this systematic review aims to describe the consequences of ed crowding for emergency patients, emergency care providers, and healthcare systems. the findings are anticipated to provide inputs to decision-makers for a better understanding of the effects of ed crowding and to contextualize practical solutions to improve the quality of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h r. rasouli et al. 2 figure 1: study selection flowchart. medical emergency services. 2. methods: 2.1. search strategy in this review, we adopted the definition for “crowding” from the american college of emergency physicians which states “crowding occurs when the identified need for emergency services exceeds available resources for patient care in the emergency department, hospital, or both.” then, we searched for articles related to crowding in eds and its major outcomes published in english between january 1, 2007, and january 1, 2019, in pubmed (medline) and embase electronic databases. we applied search terms based on common keywords in the literature concerning the consequences of emergency department crowding (table 1). we used suitable combinations of "or" and "and" in all databases. also, we searched google scholar and google to find relevant papers. 2.2. data collection and quality assessment two reviewers (hr.r. & a.ae.), independently screened the titles, abstracts and the methodological validity of the records using data extraction format before their inclusion in the final review. discussions with the senior author (m.e) were used to resolve any disagreements among the reviewers during the assessment phase. the inclusion criterion was: all studies evaluating the effects and consequences of ed crowding. however, a study was excluded if it only reported the outcomes of a case report or systematic review investigations. a total of 73 articles were eligible for the review (figure 1). we further assessed the records using the standardized critical appraisal skills programme (casp) for the cohort studies, and qualitative studies. besides, the joanna briggs institute meta-analysis of statistics assessment and review instrument ( jbi-mastari) for studies which employed other designs was used (7). we addressed prisma checklist requirements. finally, after excluding 15 records with eligibility assessment scores below 0.33 points (<33%), the final review was done on 59 records. throughout the processes, we attempted to maintain the original intentions of authors such as effects on patients, effects on healthcare delivery process, effects on quality care, and effects on efficiency in service delivery. ethics approval and consent: the research protocol was approved by the review committee of the baqiyatallah university of medical sciences. 3. results: our search initially retrieved 158 studies. however, 132 papers were excluded by reviewing title and abstract and assessing full-text due to non-relevance. then, 15 studies were excluded after final quality measurement and scoring for primary screening due to receiving below 0.33 points (<33%). finally, 58 eligible peer-reviewed original articles were included in the final review (figure 1 and table 2). the consequences of patient crowding in hospitals are multifaceted involving effects related to patient health outcomes, healthcare delivery system and the community at large. table 3 presents a summary of the commonly reported outcomes of ed crowding. ed crowding leads to delayed care for emergency patients and risk of not being visited by clinical care providers in a timely manner (8-14). the patients may react to prolonged stay to get services and to the crowding by frequent walkouts (15). the worsening of their illness (16) could result in frequent re-admissions (17, 18), prolonged hospitalizations (16, 19, 20), and related costs (21). dissatisfaction of emergency patients (22-25), medication errors and adverse events (26-29), and patient death (16, 17, 19-21, 30-36) were also common consequences. the response to emergency and non-emergency patients influences the quality of services provided, patients’ outcomes and the healthcare system. discharge of patients even with high-risk clinical features (17) and diverting the patients to other facilities (37) might have affected the health outcomes. these conditions not only decrease admission rates (38) and prolong the time to receive and transfer outpatients (39), but also compromise the patients’ health outcomes and lead to high admission and re-admission rates (22, 36, 40) followed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e52 table 1: keywords used for searching published articles in databases emergency department related concepts crowding related concepts outcome related concepts controlled phrases keywords controlled term/phrase keywords keywords pubmed emergency medicine, pediatric emergency medicine, hospital emergency service, emergency medical services emergency, emergency medicine, pediatric emergency medicine, emergency medical services, emergency room, hospital emergency services, emergency health services, emergency department, emergency ward, er, ed crowding crowding, overcrowded, crowded overcrowding, divert, diversion, congestion, surged, surging, capacity, crises, crisis, occupancy, hospital bed utilization, bed, utilization left without being seen (lwbs), length of stay (los), delayed treatment, satisfaction, adverse events mortality, morbidity, error, hospitalization, quality, performance, readmissions, overutilization, efficiency, cost embase emergency ward, emergency medicine crowding, hospital bed utilization by a decrease in discharge rate of patients (17). in addition, the prolonged hospitalization of patients leads to overutilization of diagnostic and other laboratory facilities (40). the crowding of the eds negatively influences both the healthcare delivery process and the outcomes. the high workload (41) results in delayed service provision, delayed clinical decision making, and increased length of stay (los) of patients (20, 21, 31, 35, 36, 40-54). these situations negatively influence the quality of services and efficiency (8, 14, 16, 36, 55-58). a properly managed medical emergency contributes to the prevention of the event in communities. for example, a successfully treated patient with communityacquired pneumonia will be less likely to transmit the disease to other community members (13). 4. discussion this systematic review synthesized the outcomes related to ed crowding in hospitals. crowding of ed can result in consequences for emergency patients’ health outcomes, the healthcare delivery system, and the community at large. the high inflow of emergency patients to ed leads to crowding of the ed, which can in turn negatively affect the healthcare delivery process and outcomes. delayed emergency healthcare service provision and patients leaving without being seen (lwbs) (8-14) have been commonly identified as consequences of crowding. this condition could inevitably lead to increased walkout of patients due to the perceived high length of stay. as a result, the emergency patients’ morbidity worsened, and subsequent mortalities increased (16, 17, 19-21, 30-36). the frequent readmissions and prolonged hospitalizations of emergency patients not only increase ed crowding, but also negatively affect the cost of treatment (21) and patient satisfaction (22-25). hoot and aronsky in their systematic review identified a direct relationship between ed crowding and emergency patient death, reduced quality of care, and increased treatment costs (59). delayed patient assessment and care provision could result in increased mortality, medical error, and decreased patient satisfaction (60). the increase in the workload of emergency healthcare staff due to the high patient flow results in delayed clinical decision making and emergency healthcare service provision and increased ed los of patients (20, 21, 31, 35, 36, 40-42, 44-54, 61, 62). this condition again leads to discharge of patients even with high-risk clinical features (17) and to the diversion of emergency patients to other health facilities (37). ed crowding can also be associated with decreased admission rates (38), delayed emergency healthcare provision, and delay in transfer of emergency patients to inpatient wards (39). in contrast, the high admission and re-admission rates of emergency patients (22, 36, 40) followed by a decreased patient discharge rates (17) and prolonged hospitalization can lead to overutilization of diagnostic imaging and laboratory tests (40). thus, several emergency healthcare-related consequences seem to be overlooked in the morley et al. synthesis as they mainly focused on inpatient los and ed los (60). our review broadly highlighted the healthcare delivery system-related consequences of ed crowding under the categories of healthcare delivery process, quality care, and efficiency. ed crowding can negatively affect the quality of emergency healthcare. the higher the number of emergency patients, the longer the time it takes to investigate their conditions and to take supportive actions (49). these conditions can lead to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h r. rasouli et al. 4 table 2: studies examining outcomes of emergency department (ed) crowding author year study design sample quality outcome variable cremonesi, 2015 survey 54,254 patients high average per-patient cost; severity of health condition wang, 2015 prospective pilot 3139 patients high average length of stay (los); patient left without being seen (lwbs) shenoi, 2009 cross-sectional 63,780 admissions high diversion fee, 2007 cross-sectional 39,000 visits high ed volume at the time of arrival ben-yakov, 2015 cohort 9,759 patients high ed crowding; patient disposition (admission/discharge) cha, 2011 regression 125,031 patients high mean patient volume over 8-hour; hospital mortality chang, 2017 longitudinal 2,619 hospitals high los for admitted patients chiu, 2017 cohort 70,222 visits high ed occupancy status; decision-making time; los; patient disposition depinet, 2014 cross-sectional 9,976 patients high time to critically abnormal vital sign reassessment; patients waiting for admission, patients waiting in the lobby derose, 2014 cohort 136,740 patients high inpatient mortality; ed los dubin, 2013 retrospective 69 patients high emergency physician (ep) errors; number of patients boarding at the time of patient disposition epstein, 2012 cohort 533 patients high occurrence of preventable medical errors; ed occupancy fee, 2011 cross-sectional 486 patients high arrival-to-antibioticadministration times; number of ed patients requiring admission at the time of arrival gabayan, 2015 cohort 625,096 visits high inpatient admission; death within 7 days gaieski, 2017 cohort 2913 patients high ed occupancy; waiting patients; time to antibiotics; mortality hong, 2013 cross-sectional 1296 patients high delayed resuscitation efforts; hospital mortality hsia, 2013 cross-sectional 3,368,527 patients high ed crowding; bounceback admission hwang, 2008 cross-sectional 1,068 patient high number of admitted patients; pain care measures jo, 2012 cross-sectional 477 cases high 28-day mortality; timeliness of antibiotic therapy jo, 2014 cross-sectional 54,410 patients high emergency department occupancy ratio; ed los jo, 2015 cross-sectional 1801 patients high ed occupancy ratio; inpatient mortality this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e52 table 2: studies examining outcomes of emergency department (ed) crowding risk factor term n (%) preterm n (%) p value kennebeck, 2011 cohort 190 patients high ed crowding; timeliness of antibiotic administration kulstad,2009 cross-sectional 17 patients high time to the first electrocardiogram (ecg); time to patient arrival in catheterization laboratory; occupancy rate kulstad, 2010 observational na high average daily occupancy rate and the emergency department work index (edwin) score; number of medication errors lee, 2012 prospective review 11491 adults high ed crowding mccarthy, 2009 cohort 4 eds high crowding at 30-minute intervals throughout each patient’s ed stay; waiting room time; treatment time; and boarding time; occupancy rate mccusker, 2014 cohort 677,475 patients high 30-day outcomes: mortality, return ed visits, occupancy ratio separately for ed bed and waiting room patients medley, 2010 prospective review 6,640 imaging studies high number of radiology studies ordered per patient; occupancy rate michelson, 2012 cohort 198,778 visits high ed occupancy rate; return visits to the ed within 48 hours mills, 2009 cross-sectional 976 patients high administration of and delays in time to analgesia mills, 2010 prospective cohort 767 patients high ed crowding; time from triage to computed tomography (ct) read muller, 2015 cross-sectional 40 ed bed high time to initial physician assessment; and daily nursing hours mullins, 2014 ecological 4810 hospitals high lwbs; waiting times; boarding times; and los for admitted and discharged patients o’connor, 2014 pilot 500 patients high triage time; date; treatment area; time to physician initial assessment; return ed visits within 14 days pines, 2007 cohort 694 patients high delay (>4 hours from arrival) pines, 2007 cross-sectional 741 patients high ed crowding pines, 2008 cohort 1,469 patients high ed crowding (hallway placement, waiting times, and boarding times); patient satisfaction this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h r. rasouli et al. 6 table 2: studies examining outcomes of emergency department (ed) crowding pines, 2008 cohort 13,758 patients high poor care; a delay (>1 hour) from triage to first pain medication; a delay (>1 hour) from room placement to first pain medication pines, 2009 cross-sectional 4574 patients high inpatient adverse outcomes pines, 2010 retrospective cohort 1,716 patients high ed crowding; ed occupancy, waiting patients, admitted patients, and patient-hours); overall los; time to treatment reznek, 2017 retrospective 463 patients high door-to-imaging time (dit) within the 25minute goal shenoi, 2011 cross-sectional 161 patients high ed census; time to analgesic administration shin, 2013 retrospective 770 patients high ed occupancy rate; compliance sikka, 2010 correlation 334 patients high overall time to antibiotic administration sills, 2011 cross-sectional 927 patients high ed occupancy; number waiting to see an attending-level physician sun, 2013 cohort 995,379 ed visits, 187 hospitals high inpatient mortality; hospital length of stay; costs tekwani, 2013 cross-sectional 1591 surveys high ed crowding; hospital diversion status; satisfaction van der linden, 2014 cohort 169 patients high walkout from emergency van der linden, 2016 retrospective 39110 patient high time to triage; time to treatment; age; 24-h mortality; 10-day mortality. van der linden,2016 cross-sectional 49539 patient high occupancy ratio; ed occupancy; los; time to triage verelst, 2015 cohort 108,229 patients high in-hospital death; hospital; acquired morbidities; total hospital stay wang, 2017 cohort 1345 participants high ed crowding; patient real-time satisfaction. ward, 2015 cross-sectional 405 hospitals high admitted los; discharged los; boarding time; waiting time wiler, 2013 cross-sectional 87,705 visits high patient lwbs wu, 2015 cohort 852 patients high inpatient outcomes phillips, 2017 cohort 2,557 patients high ed los higginson, 2017 cross-sectional na high bed occupancy geelhoed, 2012 quasi-experimental na high mortality rates; overcrowding rates reduced emergency healthcare quality and poor healthcare outcomes, which may result in an increase in bed occupancy rate (63). besides, these conditions may negatively affect performances and result in inefficiency due to an increase in treatment costs (8, 14, 16, 36, 55, 56, 58). similarly, others also identified the negative influence of ed crowding on the cost of treatment (59) and non-adherence to best practice guidelines for emergency service provision (60). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e52 table 3: effects of crowding in emergency departments effects on patients delayed assessment or treatment; not being seen; not given care (8-14) increased walkouts due to perceived ed length of stay (los) (15) morbidity (16) frequent readmissions (17, 18) prolonged hospitalization (16, 19, 20) the high cost of treatment (21) low satisfaction (22-25) medication errors and adverse events (26-29) mortality (16, 17, 19-21, 30-36) healthcare delivery system process high workload (41) delayed service provision/decision making and increased ed los (20, 21, 31, 35, 36, 40-54) discharging patients with high-risk clinical features (17) diverting patients to other facilities to reduce load (37) high patient re-admission rate (22) decreased admission of patients due to crowding (38) decreased discharge rate of patients despite crowding (17) high patient admission rate to general wards and icu (40) overutilization of diagnostic imaging and laboratory tests (40) prolonged time to receive and transfer outpatients (39) effects on quality care shorter time to investigate patients’ conditions (49) poor infection prevention and control measures (63) low compliance with standards of care (19) compromised quality of care (12, 22, 41, 51, 57, 64-66) high bed occupancy rate effects on efficiency in service delivery poor performance, low efficiency, and high cost of care/treatment (8, 14, 16, 36, 55, 56, 58) 4.1. strengths and limitation this systematic review synthesized original articles related to outcomes of the emergency department crowding in hospitals globally. several studies identified complex issues related to emergency department crowding. our review identified several crowding-related challenges and consequences including patient and staff reactions. the relevant original articles on ed crowding were accessed from the pubmed, embase, and google scholar databases using comprehensive search keywords. the qualities of the records have been assessed using relevant checklists and those with low quality have been excluded. our review also adds to the comprehensiveness of the view about the issues. the more explicit schematization of our synthesis compared to other existing reviews can facilitate a better understanding of the complex phenomenon. however, this review has certain limitations. it used study reports published only in english retrieved from the two mentioned sources. moreover, the reviewed studies did not have a shared definition of crowding. 5. conclusion ed crowding affects individual patients, healthcare systems and communities at large. the negative influences of crowding on healthcare service delivery result in delayed service delivery, poor quality care, and inefficiency; all negatively affecting the emergency patients’ healthcare outcomes, in turn. this review highlights the importance of response to emergencies and emergency-related crowding and preventing the consequences to better address the healthcare needs of emergency patients and increase the effectiveness of healthcare service delivery centers. 6. acknowledgements not applicable. 6.1. authors contributions all the authors have contributed to development of the concept and production of the final manuscript. authors orcids sardollah mahmoodi: 0000-0001-7077-6144 hassan goodarzi: 0000-0002-8640-6639 6.2. funding support not applicable. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h r. rasouli et al. 8 6.3. conflict of interest no conflicts of interest. 6.4. availability of data and supporting materials the datasets used and analyzed during the current study are available from the corresponding author on request. references 1. higginson i. emergency department crowding. emerg med 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emergency medicine. 2017;24(1):25-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: results: discussion conclusion acknowledgements references archives of academic emergency medicine. 2019; 7 (1): e10 or i g i n a l re s e a rc h remifentanil versus propofol/fentanyl combination in procedural sedation for dislocated shoulder reduction; a clinical trial vahid monsef kasmaee1, seyed mahdi zia zibari2, marjan aghajani nargesi2∗ 1. guilan road trauma research center, school of health, guilan university of medical sciences, rasht, iran. 2. department of emergency medicine, school of medicine, guilan university of medical sciences, rasht, iran. received: october 2018; accepted: december 2018; published online: 25 january 2019 abstract: introduction: procedural sedation and analgesia (psa) is a fundamental skill for every emergency physician. this study aimed to compare the psa characteristics of remifentanil with propofol/fentanyl combination. methods: in this double-blind randomized clinical trial, the procedural characteristics and number of failures, as well as adverse events were compared between groups treated with either remifentanil or propofol/fentanyl combination consisting of 15-60 year old patients referring to emergency department following acute anterior shoulder dislocation. results: 64 patients were randomly assigned to either remifentanil (32 cases) or propofol/fentanyl, (32 cases) groups. the two groups were similar regarding mean age, sex, and pain severity at the time of presentation to ed. the two regimens had the same efficiency regarding pain management (100% success rate). 22 (68.8%) cases in remifentanil group and 4 (12.5%) cases in propofol/fentanyl group had failed in muscle relaxation (p < 0.001). in the group receiving remifentanil, onset of action (p = 0.043) and recovery time (p < 0.001) were significantly shorter. 10 (31.3%) cases in remifentanil group and 11 (34.4%) cases in the other group experienced adverse events (p =0.790). there was a significant difference between groups regarding the type of adverse events (p = 0.003). conclusion: compared to propofol/fentanyl combination, remifentanil has equal efficiency in pain management, lower success rate in muscle relaxation, significantly higher frequency of apnea, and shorter onset of action and recovery times in psa for reduction of anterior shoulder dislocation. keywords: propofol; remifentanil; fentanyl; shoulder dislocation cite this article as: monsef kasmaee v, zia zibari s m, aghajani nargesi m. remifentanil versus propofol/fentanyl combination in procedural sedation for dislocated shoulder reduction; a clinical trial. arch acad emerg med. 2019; 7(1): e10. 1. introduction shoulder dislocation rate is around 23.9 for 100,000 population in the united states (1). analgesia and muscle relaxation are often induced for facilitating reduction. various combinations and types of drugs are used for this propose. in many institutions, the preferred method for providing adequate analgesia involves tranquilization using a combination of benzodiazepines and narcotics (2-4). propofol is a sedative drug with a dose-dependent effect used for general anesthesia. it has no analgesic properties, so it should not be used as the sole drug in moderately painful procedures. it is suitable ∗corresponding author: marjan aghajani nargesi; school of medicine, guilan university of medical sciences, rasht, iran. e-mail: marjanagn@gmail.com tel: 00989113344071 for emergency treatment because of its rapid onset and antinausea/vomiting effects (5, 6). remifentanil is a relatively new synthetic opioid with properties similar to fentanyl (2, 18). however, there is still controversy regarding the effectiveness of using remifentanil alone for procedural sedation and analgesia (psa) (7, 8). dunn et al. have introduced remifentanil as an excellent analgesic and sedative agent in psa for reduction of anterior shoulder dislocation (9). it has been reported that remifentanil has lower failure rates and higher patient satisfaction compared with fentanyl in this regard (2). searching for the best choice for psa induction resulting in higher physician and patient satisfaction and fewer adverse effects, this study was designed aiming to compare the psa characteristics of remifentanil with propofol/fentanyl combination in reduction of anterior shoulder dislocation in emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. monsef kasmaee et al. 2 2. methods 2.1. study design and setting the present study is a double-blind randomized clinical trial performed on patients with anterior shoulder dislocation presenting to poursina hospital, rasht, iran, from january to august 2017, to compare the psa characteristics of remifentanil with propofol/fentanyl combination. the study protocol was approved by ethics committee of guilan university of medical sciences under the number ir.gums.rec.1396.271 and registered on iranian registry of clinical trials under the number irct20110818007369n6. researchers adhered to the principles of helsinki ethical recommendations and confidentiality of patients’ information throughout the study period. 2.2. participants patients with acute anterior shoulder dislocation aged between 15-60 years were included in this study. those with fracture-dislocation of the shoulder joint and history of surgery, except for patients with hill-sachs lesions, as well as patients with decreased consciousness and unstable hemodynamic status, hypotension (sbp <90), history of heart disease, and allergy to soy and eggs were excluded. 2.3. procedure after careful history taking and physical examination, eligible patients underwent continuous cardiac, respiratory, blood pressure, and consciousness monitoring throughout the procedure. patients were randomly assigned to either remifentanil or propofol/fentanyl group using block randomization method. for the first group, a combination of propofol (1 mg/kg, produced by daroopakhsh company, tehran, iran) + fentanyl (1 µg/kg, produced by daroopakhsh company, tehran, iran) and for the second group, remifentanil (1 µg/kg, produced by hameln, germany) were administered, intravenously. 0.5 mg/kg propofol for propofol/fentanyl group and 0.5 µg/kg remifentanil for remifentanil group were considered as rescue dose. in case of problem in muscle relaxation, 0.5 mg/kg propofol was administered regardless of the group. patients, the physician, and the statistical analyzer were blinded to the type of drug injected. all reductions were performed by emergency medicine residents and trained nurses in charge of patients using traction countertraction method. 2.4. data gathering a checklist containing demographic data (age, sex); pain severity before, during, and after reduction; onset of drug action; time to recovery; muscle relaxation; need for rescue doses; and adverse events was filled out for each participant by a senior emergency medicine resident under supervision of an emergency medicine specialist. severity of pain was measured via visual analogue scale (vas). in this study, success was defined as ≥ 3 points decrease in pain severity on vas and recovery time was defined as time interval between dislocation reduction and complete orientation of patients. 2.5. outcome success rates in pain management and muscle relaxation were considered as main outcomes and adverse events as well as onset of action and recovery times as secondary outcomes. 2.6. statistical analysis data were analyzed using spss software version 18 and with intention to treat analysis method. independent t-test, chisquare and fisher’s exact tests were used for comparisons. normality of the data was measured by the ks test. in this study, p = 0.05 was considered as significance level. findings were presented as mean ± standard deviation or frequency and percentage. 3. results 3.1. baseline characteristics of patients 64 patients were randomly divided into 2 groups of remifentanil (32 cases) and propofol/fentanyl, (32 cases). mean age of patients was 34.28 ± 10.84 years in remifentanil group and 35.43 ± 14.25 years in the propofol/fentanyl group (p = 0.716). table 1 compares the baseline characteristics of the two groups. the groups were similar regarding mean age, sex, and pain severity on presentation to ed. 3.2. outcomes table 2 compares the studied outcomes between groups. as table 2 and figure 1 show, although the severity of pain during and 20 minutes after reduction was statistically different between the two groups, it was not clinically important. in other words, the two regimens have similar effectiveness in pain management (100% success rate). 22 (68.8%) cases in remifentanil group and 4 (12.5%) cases in propofol/fentanyl group had failure in muscle relaxation and needed additional dose/s of propofol for muscle relaxation (p < 0.001). remifentanil receiving group had a significantly lower onset of action (p = 0.043) and recovery time (p < 0.001). 10 (31.3%) cases in remifentanil group and 11 (34.4%) cases in the other group experienced adverse events (p =0.790). there was a significant difference between groups regarding the type of adverse events (table2; p = 0.003). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e10 table 1: baseline characteristics of the two studied group variable remifentanil propofol/fentanyl p sex male 11 (34.4) 5 (15.6) 0.083 female 21 (65.6) 27 (84.4) age (year) less than 30 11 (34.4) 14 (43.8) 31-40 12 (37.5) 9 (28.1) 0.674 41-60 9 (28.1) 9 (28.1) pain severity ( vas) on presentation to ed 6.2 ± 1.9 7.3 ± 3.2 0.110 data are presented as mean ± standard deviation or frequency (%) vas: visual analogue scale. table 2: comparison of studied outcomes between groups variable remifentanil propofol/fentanyl p pain severity ( vas) during reduction 1.06 ± 0.35 2.40 ± 1.34 < 0.001 20 minutes after reduction 1.15 ± 0.36 1.59 ± 0.79 < 0.001 success rate pain management 32 (100.0) 32 (100.0) na muscle relaxation 10 (31.3) 28 (87.5) < 0.001 adverse events agitation 0 (0.0) 8 (25.00) 0.003 apnea 10 (31.30) 3 (9.40) time (minutes) onset of action 1.29 ± 0.48 1.96 ± 1.77 0.043 recovery 2.06 ± 1.00 5.43 ± 4.93 < 0.001 data are presented as mean ± standard deviation or frequency (%) vas: visual analogue scale. figure 1: comparison of pain severity between the groups at different studied times. 4. discussion based on the findings of the present study, compared to propofol/fentanyl combination, remifentanil is equally effective in pain management, but has lower success rate in muscle relaxation, significantly higher frequency of apnea, and shorter onset of action and recovery times in psa for reduction of anterior shoulder dislocation. these findings are similar to studies by dunn et al., phillips, swann, sacchetti, and cok oy et al., (9-12). in the study by gharavifard et al., which was performed comparing groups receiving either midazolam/fentanyl or remifentanil, the failure rate in reduction was 15 (31.3%) cases in the first group and 1 (2.1%) case in the second one (2). rai et al., studied remifentanil versus propofol for fiber optic intubation; their report indicated a shorter endoscopy and intubation time for the remifentanil group (13). maltepe and colleagues found that recovery after propofol/remifentanil administration was faster than the combination of propofol/fentanyl (14). recovery periods in ozkun et al. study were shorter than the recovery period in similar studies performed on propofol combinations (15-17). in the present study, eight cases of agitation and 3 cases of apnea in the propofol/fentanyl group, as well as 10 cases of apnea in the remifentanil group were detected. although remifentanil provided a faster recovery, it had considerable respiratory side effects. in the study by ozkun et al., remifentanil caused the most respiratory complications, yet these effects were transient and none of them required mechanical ventilation. the use of remifentanil in combination with midazolam in pediatric psa has led to high and unacceptable levels of hypoxemia (18). similar to findings of the present this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. monsef kasmaee et al. 4 study, in ozkun et al. trial none of the patients experienced nausea and vomiting after anesthesia (15). this may be due to the anti-inflammatory effects of propofol or lower doses of opioids used in these studies. it seems that use of remifentanil resulted in shorter recovery time but higher failure rate in comparison with propofol/fentanyl combination in anterior shoulder dislocation. the analgesic effects were approximately the same in both groups. although remifentanil has a shorter recovery time, the considerable respiratory side effects and the intensity of muscle stiffness after the injection, made it unsuitable for being used as the sole drug for reduction of anterior shoulder dislocation. overall, it should be stated that for choosing the proper drug for a procedure it should be considered whether the main goal is pain control or analgesia or a combination of both. it seems that for a procedure such as shoulder dislocation, which needs both analgesia and sedation for facilitating the reduction process, using remifentanil as the sole drug with the dose used in the present study is not a good choice. however, it should be noted that some opioid drugs such as fentanyl show sedative effects in higher doses. 5. conclusion based on the findings of the present study, compared to propofol/fentanyl combination, remifentanil is equally effective in pain management, but has lower success rate in muscle relaxation, significantly higher frequency of apnea, and shorter onset of action and recovery times in psa for reduction of anterior shoulder dislocation. 6. appendix 6.1. acknowledgements all the residents and teaching staff members of the emergency department are thanked for their cooperation. 6.2. author contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors’ orcids vahid monsef kasmaee: 0000-0001-8307-8476 seyed mahdi zia zibari: 0000-0002-0329-8653 marjan aghajani nargesi: 0000-0001-5613-927x 6.3. funding/support none. 6.4. conflict of interest none. references 1. zacchilli ma, owens bd. epidemiology of shoulder dislocations presenting to emergency departments in the united states. jbjs. 2010;92(3):542-9. 2. gharavifard m, tafakori a, zamani moghadam h. remifentanil versus fentanyl/midazolam in painless reduction of anterior shoulder dislocation; a randomized clinical trial. emergency (tehran, iran). 2016;4(2):92-6. 3. soysal s, karcioglu o, demircan a, topacoglu h, serinken m, ozucelik n, et al. comparison of meperidine plus midazolam and fentanyl plus midazolam in procedural sedation: a double-blind, randomized controlled trial. advances in therapy. 2004;21(5):312-21. 4. arhami dolatabadi a, mohammadian a, kariman h. lidocaine-midazolam-fentanyl combination in controlling pain for reduction of anterior shoulder dislocation; a randomized clinical trial. 2018. 2018;6(1). 5. bassett ke, anderson jl, pribble cg, guenther e. propofol for procedural sedation in children in the emergency department. annals of emergency medicine. 2003;42(6):773-82. 6. miner jr, burton jh. clinical practice advisory: emergency department procedural sedation with propofol. annals of emergency medicine. 2007;50(2):182-7. e1. 7. komatsu r, turan a, orhan-sungur m, mcguire j, radke o, apfel c. remifentanil for general anaesthesia: a systematic review. anaesthesia. 2007;62(12):1266-80. 8. scott lj, perry cm. remifentanil: a review of its use during the induction and maintenance of general anaesthesia. drugs. 2005;65(13):1793-823. 9. dunn mj, mitchell r, souza cd, drummond g. evaluation of propofol and remifentanil for intravenous sedation for reducing shoulder dislocations in the emergency department. emergency medicine journal : emj. 2006;23(1):57-8. 10. phillips wj, halpin j, jones j, mckenzie k. remifentanil for procedural sedation in the emergency department. annals of emergency medicine. 2009;53(1):163. 11. swann a, williams j, fatovich dm. recall after procedural sedation in the emergency department. emergency medicine journal. 2007;24(5):322-4. 12. cok oy, ertan a, bahadir m. remifentanil versus fentanyl in combination with midazolam for retrobulbar block in cataract surgery. saudi medical journal. 2008;29(4):5448. 13. rai m, parry t, dombrovskis a, warner o. remifentanil target-controlled infusion vs propofol target-controlled infusion for conscious sedation for awake fibreoptic intubation: a double-blinded randomized controlled trial. british journal of anaesthesia. 2007;100(1):125-30. 14. maltepe f, kocaayan e, ugurlu b, akdeniz b, guneri s. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e10 comparison of remifentanil and fentanyl in anaesthesia for elective cardioversion. anaesthesia and intensive care. 2006;34(3):353. 15. ozkan g, ince m, eskin m, erol g, kadan m, ozgur g, et al. sedoanalgesia for cardioversion: comparison of alfentanil, remifentanil and fentanyl combined with propofol and midazolam: a prospective, randomized, double-blind study. eur rev med pharmacol sci. 2016;20(6):1140-8. 16. herregods ll, bossuyt gp, de baerdemaeker le, moerman at, struys mm, den blauwen nm, et al. ambulatory electrical external cardioversion with propofol or etomidate. journal of clinical anesthesia. 2003;15(2):91-6. 17. karthikeyan s, balachandran s, cort j, cross m, parsloe m. anaesthesia for cardioversion: a comparison of sevoflurane and propofol. anaesthesia. 2002;57(11):1114-9. 18. clarke ac, chiragakis l, hillman lc, kaye gl. sedation for endoscopy: the safe use of propofol by general practitioner sedationists. medical journal of australia. 2002;176(4):158-61. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion appendix references emergency. 2017; 5 (1): e56 or i g i n a l re s e a rc h epidemiologic features and outcomes of caustic ingestions; a 10-year cross-sectional study athena alipour faz1, fahimeh arsan2, maryam peyvandi1, mahbobeh oroei3, omid shafagh3, maryam yousefi1, hassan peyvandi3∗ 1. clinical research development center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. general surgery department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. hearing disorders research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2017; accepted: february 2017; published online: 2 february 2017 abstract: introduction: caustic ingestions are among the most prevalent causes of toxic exposure. the present 10-year survey aimed to evaluate the epidemiologic features and outcomes of caustic ingestion cases presenting to emergency department. methods: this is a retrospective cross-sectional study on patients who were admitted to a referral toxicology center during 2004 to 2014, following caustic ingestion. baseline characteristics, presenting chief complaint, severity of mucosal injury, complications, imaging and laboratory findings as well as outcomes (need for icu admission, need for surgery, mortality) were recorded, reviewing patients’ medical profile, and analyzed using spss 22. results: 348 patients with mean age of 37.76 ± 17.62 years were studied (55.6% male). the mean amount of ingested caustic agent was 106.69 ± 100.24 ml (59.2% intentional). intentional ingestions (p < 0.0001), acidic substance (p = 0.054), and higher volume of ingestion (p = 0.021) were significantly associated with higher severity of mucosal damage. 28 (8%) cases had died, 53 (15.2%) were admitted to icu, and 115 (33%) cases underwent surgery. conclusion: it seems that, suicidal intention, higher grade of mucosal injury, higher volume of ingestion, lower level of consciousness, lower serum ph, and higher respiratory rate are among the most important predictors of need for icu admission, need for surgery, and mortality. keywords: caustics; epidemiology; toxicology; suicide, attempted; patient outcome assessment © copyright (2017) shahid beheshti university of medical sciences cite this article as: alipour faz a, arsan f, peyvandi m, oroei m, shafagh o, yousefi m, peyvandi h. epidemiologic features and outcomes of caustic ingestions; a 10-year cross-sectional study. emergency. 2017; 5(1): e56. 1. introduction c austic ingestions are among the most prevalent causes of toxic exposure. the most commonly ingested caustics are acidic or alkaline substances (1). ingestion of cleaning substances account for more than 200,000 annual exposures reported to the united states poison control center (2-4). 10% of adults referring with caustic ingestions expire and 1-2% of ingestions lead to stricture formation (5). children younger than 5 years account for approximately 80% of caustic ingestion cases that typically occur accidentally. in adolescents, caustic ingestion cases are generally in an attempt to commit suicide and they present ∗corresponding author: hassan peyvandi; hearing disorders research center, loghman hakim hospital, makhsus st., qazvin st., tehran, iran. email: hassan.peyvandi@gmail.com tel: 00982155419005 in more severe conditions (6, 7). dysphagia, odynophagia, drooling, vomiting, stridor, dyspnea, and oropharyngeal lesions are among the most important complaints of patients. caustic ingestion can induce acute and chronic injuries and treatment in both stages is important. the severity of tissue injury in the acute phase depends on multiple factors including the type of substance, its concentration, the ingested amount, and the duration of contact (8). in the chronic stage, treatments concentrate on preventing development of strictures and improving function of the esophagus (9, 10). loghman-hakim toxicology center is one of the big referral centers for these injuries in iran capital, tehran. therefore, the present survey aimed to evaluate the epidemiologic features and outcomes of caustic ingestion cases presenting to this center during a 10-year period. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alipour faz et al. 2 2. methods 2.1. study design and setting this is a retrospective cross-sectional study on patients who were hospitalized in loghman-hakim hospital, tehran, iran, during 2004 to 2014, following ingestion of caustic substances. the study protocol was evaluated and approved by the ethics committee of shahid beheshti university of medical sciences. all the information gathered was considered confidential and was used anonymously throughout the study. researchers adhered to all ethical principles presented in declaration of helsinki during the study period. 2.2. participants all patients who were admitted to the mentioned toxicology center following ingestion of caustic agents were enrolled using census sampling. there was not any sex, age, ethnic or etc. limitation. loghman-hakim hospital is one of the main referral centers for poisoning and intoxication emergencies in iran and patients from all over the country are referred to this hospital. therefore, this center hosts a diverse population of patients with various problems that can be considered as a national representative sample. 2.3. data gathering patients’ baseline characteristics (age, sex, clinical findings, intent of ingestion, type of caustic substance (acidic or alkaline), amount of ingested caustic (as reported by the patients or the patients’ family members), time to hospital, duration of hospitalization, duration of icu admission), presenting vital signs (systolic blood pressure, respiratory rate, pulse rate, glasgow coma scale), presenting chief complaint (vomiting, dyspnea, drooling, etc.) severity of mucosal injury on esophagogastroduodenoscopy (egd), gastrointestinal complications (perforation, strictures and fistula formation), systemic complication (acute renal insufficiency and acute hepatic failure), chest x ray findings, pathology findings, and laboratory findings (sodium, potassium, blood urea nitrogen, creatinine, aspartate aminotransferase (ast), alanine aminotransferase (alt), blood gas analysis (ph, hco3, pco2)) as well as outcomes (need for icu admission, need for surgery, mortality) were recorded reviewing patients’ medical profile. the severity of mucosal injuries was graded based on zargar’s modified endoscopic classification (11). patients with grade i burns are just monitored for 24 to 48 hours while patients with grade 2 and 3 undergo exploratory laparotomy (12-15). acute renal insufficiency was defined as glomerular filtration rate < 60 ml/min/1.73 m2 and acute hepatic failure as increased liver function tests to > 3 times the normal upper limit. a trained medical doctor was responsible for data gathering. 2.4. statistical analysis data were analyzed using spss software for windows version 22. the quantitative data were described by mean ± standard deviation and qualitative variables were presented using frequency and percentage. the associations of baseline, clinical, and laboratory variables with need for surgery, need for icu admission, and mortality were estimated using appropriate statistical tests such as chi square, fisher’s exact, t test, one way anova, or non-parametric tests. the significance level was considered p < 0.05. table 1: baseline characteristics of studied patients variable value age (year) < 18 25 (7.3) 18 – 35 144 (42) 35 – 50 97 (28.3) 50 – 65 39 (11.4) ≥ 65 38 (11.1) sex male 193 (55.6) female 154 (44.4) caustic type acidic 188 (54.0) alkaline 149 (42.8) unknown 11 (3.2) intention suicidal 206 (59.2) accidental 105 (30.2) unknown 37 (10.6) time to reach ed (hour) < 6 253 (81.87) 6 12 29 (9.38) >12 27 (8.73) presenting signs vomiting 164 (47.8) hematemesis 145 (42.3) dysphagia 88 (25.7) drooling 68 (19.8) oropharyngeal lesions 63 (18.4) dyspnea 50 (14.6) history of suicidal attempt (n =78) yes 47 (60.3) no 31 (39.7) history of psychiatric disorders (n =105) yes 72 (68.6) no 33 (31.4) vital signs on admission systolic blood pressure (mmhg) 119.76±19.26 pulse rate (/minutes) 86.29±14.72 respiratory rate (/minute) 19.08±4.98 glasgow coma scale 14.75±0.92 data were presented as mean ± standard deviation or number and percentage. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2017; 5 (1): e56 table 2: laboratory findings of the studied patients at the time of admission to emergency department variable number (%) sodium (meq/dl) < 135 12 (3.6) 135 – 145 248 (74.7) > 145 72 (21.7) potassium (meq/dl) < 3.5 10 (3.0) 3.5 – 5.5 305 (91.9) > 5.5 17 (5.1) blood urea nitrogen (mg/dl) < 20 48 (14.5) ≥ 20 284 (85.5) creatinine (mg/dl) < 1.6 326 (96.1) ≥ 1.6 13 (3.9) aspartate aminotransferase (u/l) < 40 56 (91.8) ≥ 40 5 (8.2) alanine aminotransferase (u/l) < 40 57 (95.0) ≥ 40 3 (5.0) ph <7.35 85 (33.1) 7.35 -7.45 133 (51.8) >7.45 69 (15.2) hco3 (mmol/l) < 22 128 (50.6) 22 – 26 75 (29.6) ≥ 26 50 (19.8) pco2 (mmhg) <35 99 (28.4) 35 – 45 104 (40.8) ≥ 45 52 (20.4) 3. results 3.1. baseline characteristics 348 patients with mean age of 37.76 ± 17.62 years (3 – 87) were studied (55.6% male). table 1 shows the baseline characteristics of studied patients. the mean amount of ingested caustic agent was 106.69 ± 100.24 ml (10 – 500). hydrochloric acid was the most commonly (69.8%) ingested acidic substance, which was followed by sulfuric acid (19.5%). the most common ingested alkaline was lye (46.3%). among intentional cases, 115 (56.1%) patients had used alkaline material and 90 (43.9%) acidic ones (p = 0.812). 3.2. laboratory findings table 2 summarizes the laboratory findings of studied patients. 21.7% hypernatremia, 5.1% hyperkalemia, 3.9% abnormal creatinine (≥ 1.6 mg/dl), and 8.2% abnormal liver function test were among the most important laboratory findings. serum ph revealed 33.1% acidosis and 15.2% alkalosis. 3.3. chest x ray findings 1 (0.5%) case of hemothorax, 2 (1.1%) sub-diaphragmatic free gas, 5 (2.7%) airway edema, 2 (1.1%) reticulonodular changes, and 2 (1.1%) aortic ectasia cases were among the most important chest x-ray findings, which were recorded for 186 cases. 3.4. endoscopic findings the findings of egd were available for 313 patients. the severity of esophageal mucosal damage based on zargar’s modified endoscopic classification was normal in 64 (20.4), grade i in 133 (42.5%), grade iia in 37 (11.8%), grade iib in 16 (5.1%), and grade iiia in 63 (20.1%) cases. these measures for gastric mucosal damage were 72 (25.9) normal cases, 72 (25.9%) grade i, 62 (22.3%) grade iia, 32 (11.5%) iib, 39 (14.0%) grade iii, and 1 (0.4%) grade iv. intentional ingestions (p < 0.0001), acidic substance (p = 0.054), and higher volume of ingestion (p = 0.021) were significantly associated with higher severity of mucosal damage. 3.5. pathology findings the results of pathological assessment were available for 49 (14.1%) cases, which revealed grade i injury in 13 (3.7%), grade ii in 23 (6.6%), and grade iii in 13 (3.7%) cases. 3.6. outcomes 28 (8%) cases had died (2.9% in < 24 hours of admission) and 28 (8%) cases were discharged against medical advice. the mean duration of hospital stay was 5.76 ± 6.76 (1 – 50) days. 3 (0.9%) acute renal insufficiency, 5 (1.4%) gastrointestinal perforation, 33 (9.5%) stricture formation, and 3 (0.9%) fistula formation cases were among the most important complications in the present series. 3.7. need for icu admission 53 (15.2%) were admitted to the icu for 6.32 ± 6.12 days (1 – 41). table 3 shows the correlation of different demographic, clinical, and endoscopic variables with need for icu admission. there were a significant correlation between suicidal intention (p < 0.0001), higher grade of mucosal injury on egd (p < 0.0001), volume of ingestion (p < 0.0001), delayed admission (p = 0.033), level of consciousness on admission (p = 0.001), serum ph on admission (p = 0.003), respiratory rate on admission (p = 0.035), and dyspnea (p < 0.0001) with need for icu admission. 3.8. need for surgery 115 (33%) cases were in need of surgical interventions and underwent surgery. acidic caustic agent (p = 0.027), suicidal intention (p < 0.0001), higher grade of mucosal injury on egd (p < 0.0001), volume of ingestion (p = 0.010), level of conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alipour faz et al. 4 table 3: correlation of demographic, clinical, laboratory, and endoscopic variables with need for icu admission variable icu admission p value no yes sex male 158 (81.9) 35 (18.1) 0.101 female 136 (88.3) 18 (11.7) type of caustic agent alkaline 164 (87.2) 24 (12.8) 0.114 acidic 122 (81.9) 27 (18.1) intention accidental 100 (95.2) 5 (4.8) < 0.001 suicidal 165 (80.1) 41 (19.9) history of psychiatric disease yes 53 (73.6) 19 (26.4) 0.068 no 30 (90.9) 3 (9.1) esophageal injury (endoscopic) grade i 127 (95.5) 6 (4.5) grade iia 31 (83.8) 6 (16.2) < 0.001 grade iib 13 (81.3) 3 (18.8) grade iiia 34 (54.0) 29 (46) gastric injury (endoscopic) grade i 68 (94.4) 4 (5.6) grade iia 56 (90.3) 6 (9.7) grade iib 23 (71.9) 9 (28.1) < 0.001 grade iii 27 (69.2) 12 (30.8) grade iv 0 (0.0) 1 (100) serum ph on admission < 7.35 62 (72.9) 23 (27.1) 7.35 – 7.45 120 (90.2) 13 (9.8) 0.003 > 7.45 33 (84.6) 6 (15.4) dyspnea yes 18 (64) 35 (36) < 0.001 no 258 (88.1) 35 (11.9) mean age (year) 37.19 ± 17.86 40.92 ± 16.00 0.160 delayed admission (hour) 3.37 ± 3.98 4.76 ± 5.1 0.033 volume of ingestion 96.16 ± 90.03 165.57 ± 131.03 < 0.001 glasgow coma scale on admission 14.85 ± 0.55 13.91 ± 2.21 0.001 respiratory rate (/minute) 18.85 ± 4.57 20.52 ± 6.91 0.035 data were presented as mean ± standard deviation or number and percentage. sciousness on admission (p = 0.0001), serum ph on admission (p = 0.001), respiratory rate on admission (p < 0.0001), and dyspnea (p = 0.001) were significantly associated with need for surgery. 3.9. mortality table 4 shows the correlation of different demographic, clinical, and endoscopic variables with mortality. there were a significant correlation between mean age (p = 0.032), suicidal intention (p = 0.002), higher grade of mucosal injury on egd (p < 0.0001), volume of ingestion (p = 0.001), level of consciousness on admission (p < 0.001), serum ph on admission (p < 0.001), and respiratory rate on admission (p < 0.001) with mortality. 4. discussion: based on the findings of present study, most cases of caustic ingestion were between 18 – 35 year old (42%), with 80% female to male ratio, 79% alkaline to acid ratio, 50% unintentional to intentional ratio, and normal to grade i mucosal injury. suicidal intention, higher grade of mucosal injury, higher volume of ingestion, lower level of consciousness, lower serum ph, and higher respiratory rate were significantly correlated with need for icu admission, need for surgery, and mortality. the sex and age distribution of the study participants were compatible with the results of paudyal et al. in nepal (16) and unmatched with the findings of istanbul study which declared the 3:1 female to male ratio of caustic ingestion (17). in this survey, alkaline substances had a higher prevalence compared to acidic soluthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2017; 5 (1): e56 table 4: correlation of demographic, clinical, laboratory, and endoscopic variables with mortality variable mortality p value no yes sex male 179 (92.7) 14 (7.3) 0.557 female 410 (90.9) 14 (9.1) type of caustic agent alkaline 173 (92.0) 15 (8.0) 0.844 acidic 136 (91.3) 13 (8.7) intention accidental 103 (98.1) 2 (1.9) 0.002 suicidal 182 (88.3) 24 (11.7) history of psychiatric disease yes 61 (84.7) 11 (15.3) 0.771 no 29 (87.9) 4 (12.1) esophageal injury (endoscopic) grade i 130 (97.7) 3 (2.3) grade iia 36 (97.3) 1 (2.7) < 0.0001 grade iib 14 (87.5) 2 (12.5) grade iiia 48 (76.2) 15 (23.8) gastric injury (endoscopic) grade i 72 (100) 0 (0.0) grade iia 57 (91.9) 5 (8.1) grade iib 31 (96.9) 1 (3.1) < 0.0001 grade iii 27 (69.2) 12 (30.8) grade iv 0 (0.0) 1 (100) serum ph on admission < 7.35 66 (77.6) 19 (22.4) 7.35 – 7.45 128 (96.2) 5 (3.8) <0.001 > 7.45 38 (97.4) 1 (2.6) delayed admission (hour) 3.59 ± 4.28 3.48 ± 2.88 0.899 mean age (year) 37.15 ± 17.36 44.61 ± 19.37 0.032 volume of ingestion 101.68 ± 95.73 178.16 ± 134.53 0.001 glasgow coma scale on admission 14.85 ± 0.62 13.17 ± 2.56 < 0.001 respiratory rate (/minute) 18.71 ± 4.41 23.68 ± 8.34 < 0.001 data were presented as mean ± standard deviation or number and percentage. tions. arevalo-silva et al. also reported the predominance of alkaline substance in their study (1). the reason for ingestion was also found to be intentional in the majority of patients, which was associated with severe injuries. these findings were similar to cheng et al. study (18). based on the endoscopic findings, most patients (42.5%) had grade i mucosal injury in their esophagus and stomach, which was congruent with the findings of arevalo-silva et al. (1). there are numerous studies on characteristics of caustic ingestions and predictors of their poor outcome. endoscopic grading of mucosal damage is reported as a helpful tool in this regard (19). cheng and their colleagues in the study of adult caustic ingestion showed the correlation of grade iiib mucosal damage with higher morbidity rate (18). delayed admission was associated with higher need for icu admission in the present study. yeganeh and their colleagues showed that early admission can reduce the mortality rate of corrosive ingestion (20). older age had been associated with poorer clinical outcome in patients with caustic ingestion (21). caustic ingestion with suicidal intention was correlated with higher rate of mortality and poorer outcome (22). in addition, acid ingestions were associated with severe complication and higher mortality rate than alkaline in some studies (22-24). lower serum ph is reported as an indicator of severe injury in blood gas analysis of caustic ingestion cases (25). in this survey, 42.5% of patients were discharged from hospital after two days of hospitalization in observation unit and 15.2% of the patients were admitted to the icu. one third of patients needed surgery and underwent laparotomy, gastrotomy, biopsy, stent placement, and feeding jejunostomy. collectively, based on the study findings, it seems that the main predictor of poor outcome in caustic cases is intention type. if caustic ingestion happens with suicidal attempt, it would be linked with higher volume, high potent solution, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. alipour faz et al. 6 and delayed admission, all of which are indicators of poorer outcomes. planning for preventive measures may seem ineffective in intentional cases, but it would be very helpful in decreasing the unintentional ones. using cleaning and detergent agents with safe formula and keeping them away from children could be considered for minimizing the severity and number of unintentional cases. 5. limitations this is a retrospective cross-sectional study with its natural limitations that missing data is among the most important of them. 6. conclusion: it seems that, suicidal intention, higher grade of mucosal injury, higher volume of ingestion, lower level of consciousness, lower serum ph, and higher respiratory rate are among the most important predictors of need for icu admission, need for surgery, and mortality. 7. appendix 7.1. acknowledgements the authors appreciate the support of clinical research development center of loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest none. references 1. arevaloâăřsilva c, eliashar r, wohlgelernter j, elidan j, gross m. ingestion of caustic substances: a 15âăřyear experience. the laryngoscope. 2006;116(8):1422-6. 2. bronstein ac, spyker da, cantilena jr lr, green jl, rumack bh, heard se. 2007 annual report of the american association of poison control centers’ national poison data system (npds): 25th annual report. clinical toxicology. 2008;46(10):927-1057. 3. elshabrawi m, a-kader hh. caustic ingestion in children. expert review of gastroenterology & hepatology. 2011;5(5):637-45. 4. mowry jb, spyker da, brooks de, mcmillan n, schauben jl. 2014 annual report of the american association of poison control centers’ national poison data system (npds): 32nd annual report. clinical toxicology. 2015;53(10):962-1147. 5. rollin m, jaulim a, vaz f, sandhu g, wood s, birchall m, et al. caustic ingestion injury of the upper aerodigestive tract in adults. annals of the royal college of surgeons of england. 2015;97(4):304. 6. kikendall j. caustic ingestion injuries. gastroenterology clinics of north america. 1991;20(4):847-57. 7. riffat f, cheng a. pediatric caustic ingestion: 50 consecutive cases and a review of the literature. diseases of the esophagus. 2009;22(1):89-94. 8. haller jr a, gibbs andrews h, white jj, akram tamer m, cleveland ww. pathophysiology and management of acute corrosive burns of the esophagus: results of treatment in 285 children. journal of pediatric surgery. 1971;6(5):578-84. 9. thompson jn. corrosive esophageal injuries i. a study of nine cases of concurrent accidental caustic ingestion. the laryngoscope. 1987;97(9):1060-8. 10. thompson jn. corrosive esophageal injuries. ii. an investigation of treatment methods and histochemical analysis of esophageal strictures in a new animal model. the laryngoscope. 1987;97(10):1191-202. 11. zargar sa, kochhar r, mehta s, mehta sk. the role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. gastrointestinal endoscopy. 1991;37(2):165-9. 12. brunicardi f, andersen d, billiar t, dunn d, hunter j, matthews j, et al. schwartz’s principles of surgery, 10th edition: mcgraw-hill education; 2014. 13. campbell gs, burnett hf, ransom jm, williams gd. treatment of corrosive burns of the esophagus. archives of surgery. 1977;112(4):495. 14. haller ja, bachman k. the comparative effect of current therapy on experimental caustic burns of the esophagus. pediatrics. 1964;34(2):236-45. 15. hill jl, norberg hp, smith md, young ja, reyes hm. clinical technique and success of the esophageal stent to prevent corrosive strictures. journal of pediatric surgery. 1976;11(3):443-50. 16. paudyal b. poisoning: pattern and profile of admitted cases in a hospital in central nepal. jnma j nepal med assoc. 2005;44(159):92-6. 17. tufekci ib, curgunlu a, sirin f. characteristics of acute adult poisoning cases admitted to a university hospital in istanbul. human & experimental toxicology. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2017; 5 (1): e56 2004;23(7):347-51. 18. cheng h-t, cheng c-l, lin c-h, tang j-h, chu y-y, liu n-j, et al. caustic ingestion in adults: the role of endoscopic classification in predicting outcome. bmc gastroenterology. 2008;8(1):31. 19. cabral c, chirica m, de chaisemartin c, gornet j-m, munoz-bongrand n, halimi b, et al. caustic injuries of the upper digestive tract: a population observational study. surgical endoscopy. 2012;26(1):214-21. 20. yeganeh r, peyvandi h, mohajeri m, bashtar r, bashashati m, ahmadi m. investigation of mortality after corrosive ingestion: a prospective study. acta medica iranica. 2009;47(1):15-9. 21. chang j-m, liu n-j, pai bc-j, liu y-h, tsai m-h, lee c-s, et al. the role of age in predicting the outcome of caustic ingestion in adults: a retrospective analysis. bmc gastroenterology. 2011;11(1):72. 22. ertekin c, alimoglu o, akyildiz h, guloglu r, taviloglu k. the results of caustic ingestions. hepatogastroenterology. 2003;51(59):1397-400. 23. poley j-w, steyerberg ew, kuipers ej, dees j, hartmans r, tilanus hw, et al. ingestion of acid and alkaline agents: outcome and prognostic value of early upper endoscopy. gastrointestinal endoscopy. 2004;60(3):372-7. 24. ducoudray r, mariani a, corte h, kraemer a, munozbongrand n, sarfati e, et al. the damage pattern to the gastrointestinal tract depends on the nature of the ingested caustic agent. world journal of surgery. 2016;40(7):1638-44. 25. cheng y-j, kao e-l. arterial blood gas analysis in acute caustic ingestion injuries. surgery today. 2003;33(7):483-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion: limitations conclusion: appendix references emergency (****); * (*): *-* copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 87 emergency (2015); 3 (3): 87-88 educational evidence based emergency medicine part 2: positive and negative predictive values of diagnostic tests saeed safari1, alireza baratloo1, mohamed elfil2, ahmed negida3* 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. faculty of medicine, alexandria university, alexandria, egypt. 3. faculty of medicine, zagazig university, zagazig, egypt. *corresponding author: ahmed negida; faculty of medicine, zagazig university, el-kanayat, el-sharkia, zagazig, egypt. tel: +201125549087; email: ahmed01251@medicine.zu.edu.eg received: june 2015; accepted: june 2015 introduction: n volume 3, number 2, pages 48-49, we explained some screening characteristics of a diagnostic test in an educational manuscript entitled “simple definition and calculation of accuracy, sensitivity and specificity" (1). the present article was aimed to review other screening performance characteristics including positive and negative predictive values (ppv and npv). ppv and npv are true positive and true negative results of a diagnostic test, respectively (2). in other words, if a subject receives a certain diagnosis by a test, predictive values describe how likely it is for the diagnosis to be correct definitions: patient: positive for disease healthy: negative for disease true positive (tp)= the number of cases correctly identified as patient false positive (fp) = the number of cases incorrectly identified as patient true negative (tn) = the number of cases correctly identified as healthy false negative (fn) = the number of cases incorrectly identified as healthy positive predictive value: positive predictive value is the proportion of cases giving positive test results who are already patients (3). it is the ratio of patients truly diagnosed as positive to all those who had positive test results (including healthy subjects who were incorrectly diagnosed as patient). this characteristic can predict how likely it is for someone to truly be patient, in case of a positive test result. positive predictive value= fptp tp  negative predictive value: negative predictive value is the proportion of the cases giving negative test results who are already healthy (3). it is the ratio of subjects truly diagnosed as negative to all those who had negative test results (including patients who were incorrectly diagnosed as healthy). this characteristic can predict how likely it is for someone to truly be healthy, in case of a negative test result. negative predictive value= fntn tn  predictive values and the prevalence of the disease: since the ratio includes both healthy and patient subjects, predictive values are affected by the prevalence of the disease and can differ from one setting to another for the same diagnostic test. the lower the prevalence of the disease, the higher its negative predictive value. on the other hand, the higher the prevalence of the disease, the higher the positive predictive value. for solving these problems, positive and negative likelihood ratios were developed, which will be introduced and discussed in part three of ebm series articles of emergency. examples: example 1: imagine we have a sample population of 100 people, 50 healthy and the others patients. if the test was positive for 75 people of this population, the ppv and npv of test are as follows: ppv: 50/75 = 0.66 or 66.6%. this means that in this population, 66.6% of people whose test result is positive, have the disease. npv: 25/25 = 100%. this means that in this population, 100% of the people whose test result is negative, are healthy (figure 1). i figure 1: a schematic presentation of an example test with 66.6% ppv, and 100% npv. copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com safari et al 88 example 2: in a study by aminiahidashti et al. (4), out of a total population of 80 cirrhotic patients, 21 (26%) had opaque ascites fluid appearance (figure 2). 15 people out of the 21 had spontaneous bacterial peritonitis (sbp). question: please calculate sensitivity, specificity, accuracy, ppv, and npv of opaque ascites fluid in prediction of sbp if the total number of sbp patients was 40 cases (50%). answer: considering the total number of 40 patients and 15 tp cases, there were 25 cases of fn. in addition, total number of negative test was equal to 59. therefore, number of tn cases: 59 – 25 = 34. based on the above-mentioned calculations, screening performance characteristics of ascites fluid appearance in prediction of sbp are as follows: sensitivity: 15/40 = 37.5% specificity: 34/40 = 85% accuracy: (15 + 34) / 80 = 61.2% ppv: 15/21= 71.4% npv: 34/59 = 57.6% example 3: in the haghighi et al. study (5), out of the 130 patients, 13 already had traumatic lens dislocation and 117 were healthy. however, ultrasonography was positive for lens dislocation in 13 cases, while 2 cases were fp (figure 3). question: please calculate sensitivity, specificity, accuracy, ppv, and npv of ultrasonography in detection of traumatic lens dislocation. answer: considering the total number of 13 patients and 2 fp cases, there were 11 tp cases. screening performance characteristics of ultrasonography in prediction of traumatic lens dislocation are as follows: sensitivity: 11/13 = 84.6% specificity: 115/117 = 98.3% accuracy: (11 + 115) / 130 = 96.9% ppv: 11/13 = 84.6% npv: 115/117 = 98.3% references: 1. baratloo a, hosseini m, negida a, el ashal g. part 1: simple definition and calculation of accuracy, sensitivity and specificity. emergency. 2015;3(2): 48-9. 2. fletcher rh, fletcher sw, fletcher gs. clinical epidemiology: the essentials: lippincott williams & wilkins; 2012. p: 127. 3. altman dg, bland jm. statistics notes: diagnostic tests 2: predictive values. bmj. 1994;309(6947):102. 4. aminiahidashti h, hosseininejad sm, montazer h, bozorgi f, jahanian f, raee b. diagnostic accuracy of ascites fluid gross appearance in detection of spontaneous bacterial peritonitis. emergency. 2014;2(3): 138-40. 5. haghighi sho, begi hrm, sorkhabi r, et al. diagnostic accuracy of ultrasound in detection of traumatic lens dislocation. emergency. 2014;2(3): 121-4. figure 3: a schematic presentation of the example 3. lens dislocation total positive negative ultrasonography positive tp = 11 fp = 2 13 negative fn = 2 tn = 115 117 total 13 117 130 figure 2: a schematic presentation of the example 2. sbp total positive negative ascites fluid appearance positive tp = 15 fp = 6 21 negative fn = 25 tn = 34 59 total 40 40 80 emergency. 2018; 6 (1): e12 le t t e r to ed i to r brain natriuretic peptides in screening of syncope with cardiac origin; a commentary hamideh feiz disfani1, mostafa kamandi2∗, kazem rahmani3 1. department of emergency medicine, mashhad university of medical sciences, mashhad, iran. 2. department of internal medicine, mashhad university of medical sciences, mashhad, iran. 3. department of epidemiology and biostatistics, iran university of medical sciences, tehran, iran received: january 2018; accepted: february 2018; published online: 18 february 2018 cite this article as: brain natriuretic peptides in screening of syncope with cardiac origin; a commentary. emergency. 2018; 6(1): e12. dear editor: syncope is a serious problem with life-time prevalence of 35% (1). it is estimated that 1 -3% of referrals to emergency departments and in-patient admissions are due to syncope (2). the underlying conditions can be cardiac or neurologic. considering the completely different circumstances ruling the encounters with cardiac and neurologic syncope, in recent years many attempts have been made to find the proper tool for differentiating cardiac and non-cardiac causes of syncope. the result of which is formation of some clinical decision rules including san francisco syncope rule (sfsr), osservatorio epidemiologico sulla sincope nel lazio (oesil), evaluation of guidelines in syncope study (egsys), risk stratification of syncope in the emergency department (rose), and boston syncope rules. the serum marker brain natriuretic peptide (bnp), which is becoming increasingly established in emergency departments for diagnosis of acute heart failure, can reflect the presence of a structural heart disease (3-5). it seems that bnp could be considered as a screening tool in detection of syncope with cardiac origin. in a study by wojtowicz j et al. who evaluated bnp in children and adolescents with syncope, there was no significant difference in terms of bnp level between the syncope and control groups (6). in contrast, zhang q et al. concluded that serum bnp is helpful in differentiating cardiac (958.78 ± 2443.41 pg/ml) and non-cardiac (31.05 ± 22.64 pg/ml) syncope (7). tanimoto k et al. considered the cut-off value of 40 pg/ml for bnp in differentiating cardiac and non-cardiac syncope and ∗corresponding author: mostafa kamandi; department of internal medicine, mashhad university of medical sciences, mashhad, iran. e-mail: mostafaakamandi@gmail.com tel: 00985138525312 found that it had 82% sensitivity and 92% specificity (8). a significant difference was observed in bnp level of the cardiac group (514 pg/ml) compared to the non-cardiac ones (182 pg/ml) in pfister et al. study (4). it seems that, more research is needed to clarify this relationship and the variables that might play the role of confounders in a causal inference. more studies on children are required because there is some controversy regarding this relationship. running studies with accurate methodology, large sample sizes, and in a multicentric fashion could be helpful in this regard. 1. appendix 1.1. acknowledgements none. 1.2. author contribution all authors pass the four criteria for authorship contribution based on the international committee of medical journal editors (icmje) recommendations. 1.3. funding/support none. 1.4. conflict of interest none. references 1. ganzeboom ks, mairuhu g, reitsma jb, linzer m, wieling w, van dijk n. lifetime cumulative incidence of syncope in the general population: a study of 549 dutch subjects aged 35–60 years. journal of cardiovascular electrophysiology. 2006;17(11):1172-6. 2. kenny ra, bhangu j, king-kallimanis bl. epidemiology of syncope/collapse in younger and older western pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. feiz disfani et al. 2 tient populations. progress in cardiovascular diseases. 2013;55(4):357-63. 3. pfister r, tan d, thekkanal j, hellmich m, schneider ca. predictors of elevated nt-pro-bnp in cardiovascular patients without acute heart failure. international journal of cardiology. 2009;131(2):277-80. 4. costantino g, solbiati m, pisano g, furlan r. nt-pro-bnp for differential diagnosis in patients with syncope. international journal of cardiology. 2009;137(3):298-9. 5. tada h, ito s, shinbo g, tadokoro k, ito i, hashimoto t, et al. significance and utility of plasma brain natriuretic peptide concentrations in patients with idiopathic ventricular arrhythmias. pacing and clinical electrophysiology. 2006;29(12):1395-403. 6. wojtowicz j, szczepanski w, bogdan a, baran m, szczurak j, bossowski a. natriuretic peptides in the evaluation of syncope in children and adolescents. scandinavian journal of clinical and laboratory investigation. 2014;74(4):301-5. 7. zhang q, jin h, qi j, yan h, du j. diagnostic value of serum brain natriuretic peptide in syncope in children and adolescents. acta paediatrica. 2013;102(5). 8. tanimoto k, yukiiri k, mizushige k, takagi y, masugata h, shinomiya k, et al. usefulness of brain natriuretic peptide as a marker for separating cardiac and noncardiac causes of syncope. american journal of cardiology. 2004;93(2):228-30. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2020; 8(1): e16 or i g i n a l re s e a rc h safety of naloxone in opioid-naive methadone intoxicated patients; a case series study seyed hamid reza shakeri1, hossein hassanian-moghaddam2,3∗, nasim zamani2,3 1. department of emergency medicine, mazandaran university of medical sciences, sari, iran. 2. social determinants of health research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of clinical toxicology, loghman hakim hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. received: november 2019; accepted: december 2019; published online: 2 march 2020 abstract: introduction: studies have shown that naloxone can cause behavioral changes in naive normal volunteers. this study aimed to investigate the possible complications of naloxone in methadone-overdosed opioid-naive patients. methods: in this pilot study, a total number of 20 opioid-naive methadone-poisoned patients underwent naloxone challenge test to receive naltrexone. 0.2, 0.6, and 1.2 mg doses of naloxone were administered on minutes 0, 5, and 15-20. the patients were followed for 30 minutes after administration of naloxone and monitored for any upsetting signs and symptoms. patients with clinical opiate withdrawal scale (cows) lower than 5 were considered not addicted and the severity of patients’ symptoms was calculated using subjective opiate withdrawal syndrome (sows). results: 20 patients with mean age of 25.5±8.09 years were evaluated (70% female). median ingested dose of methadone was 25 mg [iqr; 10 to 50 mg] and mean time interval between ingestion of methadone and naloxone challenge test was 7.1±4.9 hours. fourteen patients reported some discomfort after administration of a mean dose of 1.7±0.5 mg of naloxone lasting for a maximum of four hours. the most common patients’ complaints were headache (45%) followed by nausea (20%), agitation (20%), abdominal pain (20%), and flushing (20%). two (10%) mentioned severe panic attack and sensation of near-coming death. sows significantly correlated with female gender (p = 0.004) and time elapsed post methadone ingestion (p = 0.001). conclusion: it seems that naloxone is not a completely safe medication even in opioid-naive patients, and administrating adjusted doses of naloxone even in opioid-naive methadone intoxicated patients may be logical. keywords: naloxone; substance withdrawal syndrome; analgesics, opioid; drug-related side effects and adverse reactions cite this article as: shakeri s h r, hassanian-moghaddam h, zamani n. safety of naloxone in opioid-naive methadone intoxicated patients; a case series study. arch acad emerg med. 2020; 8(1): e16. 1. introduction naloxone is a safe and effective rescue medication for opioid overdose, a leading cause of death, worldwide. it blocks the opioid receptors for 30-90 minutes to reverse the respiratory depression that would otherwise lead to apnea and death. serious side effects of naloxone are very rare. the most common side effect is opioid withdrawal in dependent patients, risk of which increases with larger doses of naloxone as well as the strength of drug dependency (1). ∗corresponding author: hossein hassanian-moghaddam; department of clinical toxicology, loghman-hakim hospital, south karegar avenue, kamali street, tehran 13336, tehran, iran. tel/fax: 00982155409534. e-mail: hasanian2000@yahoo.com; hassanian@sbmu.ac.ir although generally regarded to be safe, naloxone may precipitate rare side effects including body aches, fever, sweating, sneezing, yawning, nausea/vomiting, lacrimation, rhinorrhea, cramping, insomnia, chills, hot flashes, tachycardia, restlessness/irritability, tremulousness, seizure, hypo or hypertension/arrhythmias in patients with cardiac disorders, dizziness, headache, tremor, and pulmonary edema (2). although much more common in dependent patients, previous studies have shown that in naive normal volunteers, high-dose naloxone (2-4 mg/stat) can cause "rush" or "buzz", tingling/numbness of the extremities, dizziness, reluctance to move or initiate activities, abdominal pain, impaired cognitive performance, and increased tension-anxiety, anger-hostility, depression-dejection, and confusion-bewilderment subscales, which could last for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h r. shakeri et al. 2 hours (3). these symptoms were then attributed to blockage of the endogenous opioids (3). naloxone may be used to perform naloxone challenge test before administration of naltrexone, as a long term antagonist of the opioid, in opioidnaive patients (4). since naltrexone may cause life threatening conditions in opioid-dependent patients, it is essential to confirm naivety before its administration (5). while performing this practice, we noticed that some opioid-naive patients under the effect of long-acting opioids experienced severe discomfort. this study aimed to investigate the possible complications of naloxone in methadone-overdosed opioidnaive patients. 2. methods 2.1. study design and setting in this case series study, opioid-naive methadone-poisoned patients who were referred to emergency department of loghman hakim hospital, tehran, iran, and underwent naloxone challenge test to receive naltrexone during a 3month period between march and june 2019 were evaluated. the experiment was conducted with the informed consent of the human subject. ethical approval for the study was given by shahid beheshti university of medical science ethics committee (ethic code:). 2.2. participants patients who claimed not to be opioid dependent and had accidentally or intentionally (suicidal or recreational) ingested methadone (based on the obtained history), were included. the participants were those who needed opioid-antagonist administration for long times due to persistent respiratory acidosis (ph<7.2 and pco2 >52) (5). all had signs and symptoms of acute opioid toxicity and urine test results returned to be positive only for methadone. those with active liver disease and increased level of transaminases (twice the normal range), acute poisoning with complications developed before presentation (aspiration pneumonia, brain trauma, and acute lung injury), and those discharged against medical advice were excluded. 2.3. procedure in our center, the routine protocol to manage these patients is administration of naltrexone instead of naloxone to avoid long naloxone infusions and hospital stay. however, before administration of naltrexone it is necessary to make sure the patient is not opioid-dependent as he/she may not give the correct history on being naive. we administered 0.2, 0.6, and 1.2 mg doses of naloxone in minutes 0, 5, and 15-20 (6, 7). the patient was followed for 30 minutes after administration of naloxone doses and monitored for signs and symptoms including nausea and vomiting, agitation, flushing, abdominal pain and cramp, anxiety and restlessness, muscle and bone pain, and panic attack. 2.4. data gathering possible side effects as well as the patients’ characteristics (age and gender), amount of the ingested methadone, duration of the symptoms lasting after administration of naloxone, total naloxone dose administered, and treatments given were recorded by a toxicology fellow using a predesigned checklist. to confirm that the patient was not addicted, clinical opiate withdrawal scale (cows) was determined (8) and scores lower than 5 were considered not addicted. to determine the severity of patients’ symptoms, subjective opiate withdrawal syndrome (sows) was calculated (9). 2.5. statistical analysis the data was analyzed using statistical package for social sciences (spss) version 20 using kolmogorov-smirnov test, ttest, mann-whitney u test, and spearman test. p < 0.05 was considered significant. data are presented as mean ± standard deviation, median and inter quartile range (iqr), or frequency (%). 3. results 3.1. baseline characteristics of studied patients 20 patients with the mean age of 25.5±8.09 (range; 17 to 46) years were evaluated (70% female). thirteen (75%) had overdosed on methadone syrup and 7 (35%) had consumed methadone tablets. median ingested dose of methadone was 25 mg [iqr; 10 to 50 mg] and mean time between ingestion of methadone and naloxone challenge test was 7.1±4.9 (range; 2 to 24) hours. 18 (90%) patients had referred with loss of consciousness and 9 (45%) had respiratory acidosis on presentation (ph < 7.3 and pco2 > 54mmhg). mean ph and pco2 on admission were 7.2 ± 0.05 (range; 7.12 to 7.38) and 51.4 ± 3.5 (range; 46 to 58) mmhg, respectively. 3.2. side effects 14 (70%) patients reported some discomfort after administration of a mean dose of 1.7 ± 0.5 mg of naloxone (0.2 to 2 mg). their symptoms lasted for a maximum of four hours posttest. the most common symptom the patients complained about was headache (45%) followed by nausea (20%), agitation (20%), abdominal pain (20%), and flushing (20%). 2 (10%) cases mentioned severe panic attack and sensation of near-coming death. mean cows and sows scores were 2.4±1.9 and 2.4±2.4, respectively. sows significantly correlated with female gender (t test; p = 0.004) and time elapsed post methadone ingestion (spearman rho test; p=0.001; figure 1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e16 figure 1: scatter plot showing the relationship between time post methadone ingestion and severity of subjective opiate withdrawal syndrome (sows). 4. discussion naloxone is a derivative of natural plant alkaloid and is similar to oxymorphone. naloxone, however, is a competitive antagonist of the opiate receptors and has particularly high affinity for the îij opiate receptor and can displace morphine and other full agonists, thereby reversing their effects (10). in 2015 the american association of poison control centers reported no fatalities due to naloxone other than buprenorphine/naloxone combinations (11). although post naloxone administration complications had been previously reported in opioid-naive normal volunteers (3), these symptoms were mainly behavioral and had been attributed to the effect of the endo-morphines. this is the first study reporting complications after administration of naloxone in methadone-overdosed opioid-naive patients. the low cows score shows that our patients were not really opioid dependent. however, they showed a series of inadvertent reactions after naloxone administration. this may be due to mu receptors developing tolerance during the time elapsed between methadone ingestion and naloxone administration. in fact, it seems that the receptors have justified themselves to the high methadone concentration, while administration of naloxone reverses this transient tolerance and causes patient discomfort. this may show that despite what was previously alluded naloxone is not a very safe medication even in opioid-naive patients. therefore, administrating adjusted doses of naloxone even in naive patients seems logical. we had a small sample size because we ran a pilot on only 20 patients. future studies on larger sample sizes are warranted to better elucidate the effect of naloxone on opioid-naive patients. 5. conclusion it seems that naloxone is not a completely safe medication even in opioid-naive patients, and administrating adjusted doses of naloxone even in opioid-naive methadone intoxicated patients may be logical. 6. declarations 6.1. acknowledgements none. 6.2. author contribution all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids seyed hamid reza shakeri: 0000-0002-2111-1522 hossein hassanian-moghaddam: 0000-0003-4370-0544 nasim zamani: 0000-0002-2091-0197 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h r. shakeri et al. 4 6.3. funding/support none. 6.4. conflict of interest none. references 1. naloxone: frequently asked question. available from: http://naloxoneinfo.org/sites/default/files/frequently %20asked%20questions-naloxone_en.pdf. 2. naloxone side effects. available from: https://www.drugs.com/sfx/naloxone-side-effects.html. 3. cohen m, cohen r, pickar d, weingartner h, murphy d, bunney jr w. behavioural effects after high dose naloxone administration to normal volunteers. the lancet. 1981;318(8255):1110. 4. aghabiklooei a, hassanian-moghaddam h, zamani n, shadnia s, mashayekhian m, rahimi m, et al. effectiveness of naltrexone in the prevention of delayed respiratory arrest in opioid-naive methadone-intoxicated patients. biomed research international. 2013;2013. 5. hamdi h, hassanian-moghaddam h, hamdi a, zahed ns. acid-base disturbances in acute poisoning and their association with survival. journal of critical care. 2016;35:84-9. 6. khosravi n, zamani n, hassanian-moghaddam h, ostadi a, rahimi m, kabir a. comparison of two naloxone regimens in opioid-dependent methadone-overdosed patients: a clinical trial study. current clinical pharmacology. 2017;12(4):259-65. 7. ostadi a, zamani n, hassanian-moghaddam h, khosravi n, shadnia s. comparison of 2 naltrexone regimens in the maintenance therapy of acute methadone overdose in opioid-naive patients: a randomized controlled trial. crescent journal of medical and biological sciences. 2019;6(1):1-5. 8. clinical opiate withdrawal scale. available from: https://www.drugabuse.gov/sites/default/files/files/ clinicalopiatewithdrawalscale.pdf. 9. subjective opiate withdrawal scale. available from: https://www.asam.org/docs/default-source/educationdocs/sows_8-28-2017.pdf?sfvrsn=f30540c2_2. 10. naloxone. available from: https://livertox.nih.gov/ naloxone.htm. 11. mowry jb, spyker da, brooks de, zimmerman a, schauben jl. 2015 annual report of the american association of poison control centers’ national poison data system (npds): 33rd annual report. clinical toxicology. 2016;54(10):924-1109. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2023; 11(1): e52 rev i ew art i c l e non-pharmacologic interventions in covid-19 pandemic management; a systematic review koorosh etemad1, parisa mohseni2, saeideh shojaei1, seyed ali mousavi3, shakiba taherkhani1, fatemeh fallah atatalab1, hadis ghajari1, seyed saeed hashemi nazari1, manoochehr karami1, neda izadi1, mahmoud hajipour4∗ 1. department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 2. fertility and infertility research center, hormozgan university of medical sciences, bandar abbas, iran. 3. department of public health, shoushtar faculty of medical science, shoushtar, iran. 4. pediatric gastroenterology, hepatology and nutrition research center, research institute for children’s health, shahid beheshti university of medical sciences, tehran, iran. received: may 2023; accepted: june 2023; published online: 23 july 2023 abstract: introduction: different countries throughout the world have adopted non-pharmacologic interventions to reduce and control sars cov-2. in this systematic approach, the impact of non-pharmacologic interventions in management of covid-19 pandemic was assessed. methods: following preferred reporting items for systematic reviews and metaanalyses (prisma) guidelines, systematic search was carried out on the basis of a search strategy on pubmed, web of science, scopus, and who databases on covid-19. the impact of travel ban, personal protective equipment, distancing, contact tracing, school closure, and social distancing and the combined effect of interventions on covid-19 were assessed. results: of the 14,857 articles found, 44 were relevant. studies in different countries have shown that various non-pharmacological interventions have been used during the covid-19 pandemic. the travel ban, either locally or internationally in most of the countries, movement restriction, social distancing, lockdown, personal protective equipment (ppe), quarantine, school closure, work place closure, and contact tracing had a significant impact on the reduction of mortality or morbidity of covid-19. conclusion: evidence shows that the implementation of nonpharmacologic interventions (npis), for example, social distancing, quarantine, and personal protective equipment’s are generally effective and the best way to prevent or reduce transmission. however, this study suggests that the effectiveness of any npi alone is probably limited, thus, a combination of various actions, for example, social distancing, isolation, and quarantine, distancing in the workplace and use of personal protective equipment, is more effective in reducing covid-19. keywords: physical distancing; quarantine; social isolation; covid-19; sars-cov-2; prevention and control; systematic review cite this article as: etemad k, mohseni p, shojaei s, mousavi sa, taherkhani s, et al. non-pharmacologic interventions in covid-19 pandemic management; a systematic review. arch acad emerg med. 2023; 11(1): e52. https://doi.org/10.22037/aaem.v11i1.1828. 1. introduction the recent surge of a novel coronavirus (2019-ncov or sarscov-2, which causes covid-19) was started in december 2019 in wuhan, china, and was introduced by the world health organization as a pandemic and public health issue [1, 2]. the victims of this disease are all humans, and covid∗corresponding author: mahmoud hajipour; pediatric gastroentrology, hepatology and nutrition research center, research institute for children’s health, shahid beheshti university of medical sciences, tehran, iran. e-mail: m.hajipour.13@gmail.com, tel: +98 (21) 22431993, fax: +98 (21) 22 43 97 84, orcid: https://orcid.org/00000001-8187-9114. 19 not only disturbed the health systems of all countries, but also disrupted the balance of socioeconomic systems [3]. by the time of writing this article (3 may 2023), based on the dashboard statistics report of who, there were 765,222,932 definite diagnoses and 6,921,614 deaths caused by covid19, worldwide [4]. over a century has passed since the last time a pandemic (influenza pandemic h1n1) had occurred without access to the vaccine in the world [5]. according to john hopkins university report, in the absence of health interventions, covid-19 could cause 40 million deaths in the world in 2020 [2]. although similar to many viral diseases, medication therapy seems to be a viable solution to control the pandemic infecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 2 tion, there is no definitive treatment to cure covid-19 infection and the treatments are almost supportive and to eliminate symptoms of the disease [6]. in the absence of proper treatment and effective vaccines, non-pharmacologic interventions (npis) can be considered as the main pillar of pandemic control [7]; npis can cover a wide range of measures, generally in four groups: 1. personal protective equipment’s such as using mask and hand hygiene; 2. environmental measures such as disinfecting and ventilation; 3. social distancing in public places and school closure; 4. the actions associated with travel ban [8]. one of the main objectives of non-pharmacologic interventions was reducing the average number of infections generated at time by any infected cases during the infection period as well as the reduction of the incidence of infection and mortality rates [9]. the results of some studies show that lock down has led to 42% to 81% reduction in disease transmission cases [9-11]. it is, therefore, necessary to conduct an assessment of the effectiveness of npis, most of which are local or within a country; however, the evidence obtained from these studies is not yet conclusive as to which npi was specifically effective [12]. due to heterogeneity in the intensity and quality of the npis in different countries, the effectiveness of these methods is different so that the results of some studies suggest that the complete lock down at the national level has contributed to a drop of 81% (ci95%: 75-78) in the transfer of new cases [13]. some other studies have described social distancing and travel ban as ineffective and school closure, wearing face masks, and quarantining cities (at the same time) as better methods than complete lock down [14]. an overall and comprehensive evaluation of these measures is necessary to determine the effectiveness of each of the npis, thus, this study was carried out with the aim of “evaluating non-pharmacologic interventions of covid-19 in the world ". 2. methods 2.1. search strategy a systematic search was performed in pubmed, web of science, scopus, and who databases on covid-19, from february 2020 to may 2021, in english. two researchers independently searched for studies. pico included: participants: countries that used nonpharmacological interventions, interventions: nonpharmacologic interventions, comparison: countries that did not use npis for epidemic control, outcomes: effectiveness of npis on covid-19 outcomes such as morbidity and mortality and disease transmission; study design: observational studies such as cohort, case-control, and community trail. the database searches were conducted using the keywords shown in table 1. 2.2. inclusion and exclusion criteria the inclusion criteria were as follows: 1) studies published in english, 2) studies that included the desired indicators and interventions. the exclusion criteria were as follows: 1) duplicate articles, 2) gray literature such as non-peer-reviewed dissertations, conference proceedings/papers, letters, news, editorials, and so forth. 2.3. study selection and data collection after retrieving articles from the mentioned databases and eliminating duplicate articles, two authors conducted the screening and data collection process, independently, based on inclusion criteria. the following information was extracted from the selected studies: the first author’s name, year of publication, place of study, country of origin, aim of the study, interventions (school closing, workplace closing, public event cancelation, social gathering restrictions, public transport closure, stay-at-home requirements, internal movement restrictions, international travel restrictions, public information campaigns, testing policies, contact tracing policies, and facial covering policies) and outcome (morbidity rate, mortality rate, disease transmission rate, hospitalization rate, basic reproduction number rate). 2.4. quality assessment the quality assessment was performed by two reviewers that assessed the quality of data in the included studies. we used the preferred reporting items for systematic reviews and meta-analyses (prisma) checklist to ensure the quality of selected studies. after a full-text quality assessment of selected studies, studies with high and medium quality were included in the analyses and finally, the key findings were extracted. 2.5. risk of bias and certainty of evidence assessment the colleagues who cooperated in the search of articles and data extraction are all epidemiologists and also received the necessary training before starting the study; and in several sessions, based on the knowledge and science of the panel members, who were all epidemiologists, the articles for the next stage were selected and then checked for quality. in addition, since the heterogeneity between the studies regarding the outcomes and types of studies was high, the authors decided not to perform a meta-analysis and to be satisfied only with a systematic review. 2.6. data analysis meta-analysis was not feasible due to the heterogeneous set of interventions studied, as well as substantial differences in study designs, outcomes, and effect measures. we described results narratively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 3 archives of academic emergency medicine. 2023; 11(1): e52 3. results of the 14,857 articles found, 44 were relevant. the study selection process is shown in figure 1. studies in different countries have shown that various non-pharmacological interventions have been used during the covid-19 pandemic. the effects of these interventions on various epidemiological outcomes including morbidity, mortality, and disease transmission were systematically evaluated and the following results were obtained. 3.1. travel ban most studies were consistent in the travel ban intervention. thus, the travel ban, either locally or internationally, had a significant impact on the reduction of new cases of covid19 in most countries. in the bendavid study (2021), travel ban intervention in germany at the local level and the netherlands at the international level, and italy and the united states at the local and international levels had a significant effect on reducing new cases of covid-19 [15]. the costantino and et al. (2020) study also showed that travel restrictions were very effective in curbing the covid-19 epidemic in australia at the peak of the epidemic wave from china (when covid-19 was predominantly in china), reducing the incidence of new cases and death up to 87% [16]. 3.2. social distancing in a longitudinal pretest – posttest study, 0.9% reduction in the daily new cases of covid-19 was found, 4 to 21 days after applying social distancing intervention in the united states [17]. another study in the united states and 134 other countries found an overall 65% reduction in the spread rate of covid-19 cases after 2 weeks of social distancing intervention (which included the closure of non-essential workplaces and schools, as well as policies for physical distancing when attending a gathering) [18]. also, in another study, which was performed as a cohort and examined the number of infected people (based on syndromic symptoms diagnosis) in two similar groups in terms of basic characteristics but different in terms of location and social distancing intervention (soldiers’ barracks). in the first group, 15% were exposed to sars-cov-2 cases and their symptoms were zero, but in the second group, 64% were exposed, 27% of whom had symptoms (in the same time period and barracks) [19]. table 2 shows impact of social distancing interventions on covid19 in different countries. 3.3. lockdown in lock down intervention, most studies were consistent; for example, in bendavid (2021), lockdown in france, the united states, iran, germany and the netherlands significantly reduced the number of new cases [15]. also, 81% reduction in rate of transmission (rt) in europe (data from 11 european countries) [9] and 50% reduction in reproduction number (r0) in australia [16] were the effects of lockdown over the time. table 3 shows the impact of lockdown on covid-19 in different countries. 3.4. isolation only one study examined the impact of segregation policies on the spread of covid-19. a study by huang et al. (2020), with dynamic modeling of disease transmission in wuhan province, china, found that full case identification and isolation can reduce deaths up to 92% (from 0.0166 to 0.0012 in one month ( january 28 to february 28)) [20]. 3.5. personal protective equipment the impact of personal protective equipment (ppe) intervention was examined in 3 studies. a study by yang et al. (2021) from the united states found that the use of ppe reduced the rate of transmission or proliferation (rt) by 7% in the general population and by 20% in over 65 year-olds population [11]. ta-chou ng et al. (2020) in taiwan showed a decrease in basic reproduction number (r0) from 2.5 to 1.30 after one month (april 20 to december 20, 2020) [21]. cases were reduced from 12.11 to 7.67 (per 10,000) and mortality was reduced from 0.75 to 0.22 (per 10,000) and hospitalization was reduced from 1.54 to 0.97 (per 10,000) in delaware [22]; significant decrease in transfer rate to 0.0151 in ohio (minimum interquartile range (iqr) = 0.0005 and maximum iqr = 0.0439 from january 8 to january 23, 2020) and reduction of transfer rate to 0.0639 (minimum iqr = 0.05597 and maximum iqr = 0.0637 from april 17 to may 15 ,2020) in new york were also reported [23]. 3.6. quarantine decrease in the transfer rate to 0.0603 with minimum iqr = 0.0513 and maximum iqr = 0.0708 in hubei from january 23 to february 23 and decrease in transfer rate to 0.1531 with minimum iqr = 0.1408 and maximum iqr = 0.1642 in hubei from february 2 to february 17, and the reduction of the transfer rate to 0.1798 with minimum iqr = 0.1525 and maximum iqr = 0.2055 in hubei from february 17 to march 31 has been one of the effects of quarantine intervention [23]. in wuhan, china, the r0 after the quarantine intervention was studied from june 23 to february 1 and from february 2 to february 16, which decreased from 3.8 to 1.37 and from 1.24 to 0.49, respectively [24]. 3.7. restriction of movement reducing the transfer rate to 0.0603 with minimum iqr = 0.0513 and maximum iqr = 0.0708 in china’s hubei province from january 23 to february 2 has been the effect of a movement restriction intervention [23]; in another study in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 4 wuhan, china, a traffic ban from january 10 to january 22 increased r0 from 2.91 to 3.82 [24]. 3.8. school closure existing studies show that school closures can potentially reduce transmission during an epidemic. in the study by klimek-tulwin et al. (2020), there was a statistically significant correlation between school closure with the reduction of covid-19 incidence in the general population. the countries analyzed included data from 18 countries (argentina, belgium, poland, romania, estonia, hungary, lithuania, latvia, japan, brazil, czech, finland, france, germany, italy, norway, spain, and uk) [25]. in the study by bendavid et al. (2021), single or combined non-pharmacological interventions were studied and analyzed at the general population level in england, france, germany, iran, italy, the netherlands, spain, the united states, south korea and sweden. the school closure intervention showed a significant reduction in new cases of covid-19 for sweden only [15]. 3.9. work place closure the study by bendavid et al. (2021) showed a significant reduction for new cases of covid-19 due to work place closure intervention in the united states [15]. another study in new york found that after the reduction of the business activity index from 100 to 39 in early february to late may (the average number of visits to a favorite place such as a store, restaurant, park, hospital, or museum per 1,000 people), the rate of positive cases decreased from 53.4% at the beginning of april to 4.7% at the end of may; in other words, the reduction in the daily growth of covid-19 infection rate was estimated to be 0.12 (standard linear regression coefficient) [26]. 3.10. contact tracing cases reduced from 7.51 to 3.35 (per 10,000) and mortality reduced from 0.31 to 0.09 (per 10,000) and hospitalization reduced from 0.97 to 0.53 (per 10,000) was observed after contact tracing in delaware from may 12 to january 1 2020 [22]. 3.11. mixed interventions the decrease in rt due to mixed interventions has shown different values in studies. the rt reduced from 36% to 96% in different countries based on different mixed interventions. the lowest and highest decrease belonged to quarantine and restriction movement intervention in france; and comprehensive intervention measures, social distancing, rapid reaction by the prevention and control system, use of masks, travel ban, screening and isolation of outsiders in jilin, china, respectively. table 4 shows the effects of mixed interventions on rt in details. 4. discussion in total, four studies on social distancing intervention have been carried out in korea, america, iran, and several european countries, and their studied outcomes were disease incidence, mortality, reduction of the epidemic process, and rvalue (reproductive number). in all these studies, social distancing reduced the studied outcomes. three studies were conducted on the lock down intervention in south africa, india, and spain, and their studied outcomes included: r0, the rate of disease, and the rate of death and hospitalization; and with the implementation of the intervention, the values of the studied outcomes decreased. it has been found that when the implementation of this intervention is canceled, the rate of disease attack increases. two studies have been conducted on the intervention of closing schools in the united states and several other countries, and the results of these studies showed reduction in the first wave of the epidemic and the incidence of the disease, which we observed that the sooner this intervention is implemented, the greater the reduction of daily cases. in two studies, the effect of mask use intervention in america and delaware has been investigated and, in both studies, we have observed that the use of masks reduces the daily incidence of diseases and the implementation of this intervention together with other public interventions has a significant effect on reducing cases of infection. the impact of non-pharmacologic interventions in preventing covid-19 is one of the most important and serious issues that impose uncertainty among politicians, economists, and professionals [2]. in general, since the transmission rate at the early stages of the disease is lower, the disease spreads in certain groups at the early stages of the disease, and then enters the general population in the later stages. hence, if health systems continue to identify groups at risk as soon as possible through investigation, interventions such as quarantine and contact tracing in the early stages of the epidemic may be able to slow the epidemic. however, if the disease enters the public population, population-based interventions such as travel ban, physical distancing, and . . . should be used. it is therefore necessary to draw an overall conclusion regarding the types of non-pharmacologic interventions, given the implementation of different non-pharmacologic interventions throughout the world, which impose different costs to the governments and many challenges to individuals, industries, and organizations. these studies provide a foundation for the use of targeted actions and interventions to make connection between effective factors and nonpharmacologic interventions, and reducing the transmission of the disease. it is imperative for us to apply appropriate efforts to strengthen the primary health care system in order to counter covid-19 epidemic to reduce the chances this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 5 archives of academic emergency medicine. 2023; 11(1): e52 of other epidemics in the future [2]. a better understanding of non-pharmaceutical interventions will help politicians learn how to implement interventions at the regional level [27]. in general, the purpose of non-pharmacologic interventions is to decrease transmission (r0) and reduce r0 to < 1 or to keep the disease in manageable condition [28]. all countries have implemented non-pharmacologic interventions to control covid-19. however, there is a significant shift in the amount and type of implemented interventions. in some countries, only some interventions such as travel ban and quarantine are implemented, but in others, a combination of types of interventions, such as school closure, travel ban, lock down, and . . . are implemented. the impact of any intervention alone may be limited, but a combination of these interventions can be very effective and have a huge impact on reducing the transmission of disease, exhaustion of the health care system, and mortality due to the disease. in a study in china it was mentioned that without non-pharmacologic interventions, the number of cases diagnosed with the disease would be 51 times in wuhan, 92 times in hubei, and 125 times in other states [29]. the results of the study conducted in china showed that the travel ban causes 3-5 days delay in the progress and growth of the disease. a new york study also showed that the use of a mask could reduce deaths by 17%-45% over two months. a study in china showed that compliance with social distancing and the closure of the epidemic center reduced the incidence of new infection by 98.9%. while, another study showed that social distancing reduced the growth rates of definite cases of infection in five countries (australia, belgium, italy, malaysia, and south korea) by an average of 52.37%. the results of the studies show that social distancing intervention and its combination with other non-pharmacologic are correlated with the sharp reduction of rt rate of covid-19, and it seems that social distancing can be adopted as one of the primary nonpharmacologic interventions to combat the disease [30]. following up and contact tracing, and quarantining cases have been identified as highly effective guidelines in controlling new cases of covid-19. most modeling methods and the results of previous experiences of health systems from epidemics have shown that if social interactions attain their normal level, the disease can be increased again. therefore, some non-pharmacologic interventions such as social distancing should continue for several months [29]. travel ban (either partially or locally) can be very effective to curb the covid-19 epidemic, preventing a very larger epidemic. the effectiveness of the travel ban in countries with high incidence of disease is the claim [31], and the prohibition of trips from countries with high incidence of disease at the international level and from provinces with red status is defined as an attempt to control the covid-19 epidemics. in general, public-based and high-risk group interventions, such as social distancing, lock down, and personal protection equipment were more effective compared to public-based interventions including detection, contact tracing, and 14day quarantine [32, 33]. in other words, population-based interventions can be increased as a supplement to case-based and marker-based strategies to compensate the ineffectiveness of case-based interventions. however, “pandemic fatigue" resulting from the maintenance of behavioral changes, such as physical distance and covering the face, may result in reduction of population-based effects. several limitations should be considered in the conclusion of this review study: most studies were based on epidemiologic modeling, so the results may be influenced by the assumptions and the input parameters of those models. different countries with various geographical, political, economic, belief status and . . . conditions have implemented some of these interventions but the same effects were not necessarily exhibited, so generalizations should be addressed by considering all these components. various studies had no agreement on the definitions and scope of social distancing, and this may cause incorrect conclusion regarding this intervention. for example, in the study by siedner and colleagues in the united states, the cancellation of public events and school closure are defined as social distancing acts [34]; while, in the study by mcgrail et al., policies for social distancing including workplaces and school closure were not essential and physical distance when present in the public was used for preventing the transmission of the virus [18]. several factors such as population density, health care infrastructure, number of tests, weather, demographic characteristics, and other cases are likely to contribute to the extent of covid19 spread, which are not considered in these studies. different levels of intervention (county / state or country / country), percentage of coverage of interventions, and even the administrative differences of interventions (optional or compulsory) cause widespread differences in conclusions and we observe the variations in the size of effects. 5. conclusion in this study, the combined effect of case-based interventions and population-based interventions in succeeding to control covid-19 epidemics were investigated. evidence shows that the implementation of non-pharmacologic interventions, for example, social distancing, quarantine, and personal protective equipment’s are generally effective and the best way to prevent or reduce transmission. however, this study suggests that the effectiveness of any npi alone is probably limited, thus, a combination of various actions, for example, social distancing, isolation, and quarantine, distancing in the workplace and use of personal protective equipment’s, is more effective in reducing covid-19 cases. in addition, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 6 both the government and the public should follow the policy of testing, tracking, and treatment as well as other public health measures, including physical distancing and use of face masks and sanitizers for safety. therefore, research helps to compare the effectiveness of interventions to provide us with more evidence for future pandemics. 6. declarations 6.1. acknowledgments we would like to express our thanks to research assistant shahid beheshtit university of medical sciences. 6.2. conflict of interest the authors declare that they have no competing interest. 6.3. funding none. 6.4. authors’ contribution parisa mohseni, saeideh shojaei, seyed ali mousavi, and shakiba taherkhani wrote the manuscript and participated in the literature review. fatemeh fallah atatalab, hadis ghajari and mahmoud hajipour participated in the literature review. koorosh etemad, seyed saeed hashemi nazari, manoochehr karami, neda izadi, and mahmoud hajipour supervised, and checked the quality of the study. all authors read and approved the final manuscript. 6.5. using artificial intelligence chatbots none. 6.6. ethics statement the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences with code: ir.sbmu.retech.rec.1400.090. references 1. lakhani hv, pillai ss, zehra m, sharma i, sodhi k. systematic review of clinical. int j environ res public health. 2020;17(12). 2. regmi k, lwin cm. impact of non-pharmaceutical interventions for reducing transmission of covid-19: a systematic review and meta-analysis protocol. bmj open. 2020;10(10):e041383. 3. chilamakuri r, agarwal s. covid-19: characteristics and therapeutics. cells. 2021;10(2). 4. world heath organisation. coronavirus disease (covid-19) pandemic 2022 [available from: https://www.who.int/data#dashboards. 5. ferguson n ld, nedjati gilani g, imai n, ainslie k, baguelin m, et al. report 9: impact of nonpharmaceutical interventions (npis) to reduce covid19 mortality and healthcare demand. imperial college covid-19 response team.2020,16 (3), 1-20. 6. el khiat a, hamdan ya, tamegart l, draoui 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shutdowns, reopening, and mask mandates. int j environ res public health. 2020;17(24):9520. 47. siqueira cads, freitas ynld, cancela mdc, carvalho m, oliveras-fabregas a, de souza dlb. the effect of lockdown on the outcomes of covid-19 in spain: an ecological study. plos one. 2020;15(7):e0236779. 48. andronico a, tran kiem c, paireau j, succo t, bosetti p, lefrancq n, et al. evaluating the impact of curfews and other measures on sars-cov-2 transmission in french guiana. nat commun. 2021;12(1):1634. 49. zhao q, wang y, yang m, li m, zhao z, lu x, et al. evaluating the effectiveness of measures to control the novel coronavirus disease 2019 in jilin province, china. bmc infect dis. 2021;21(1):1-12. 50. sugishita y, kurita j, sugawara t, ohkusa y. effects of voluntary event cancellation and school closure as countermeasures against covid-19 outbreak in japan. plos one. 2020;15(12):e0239455. 51. mahikul w, chotsiri p, ploddi k, pan-ngum w. evaluating the impact of intervention strategies on the first wave and predicting the second wave of covid-19 in thailand: a mathematical modeling study. biology. 2021;10(2):80. 52. ng t-c, cheng h-y, chang h-h, liu c-c, yang c-c, jian s-w, et al. comparison of estimated effectiveness of case-based and population-based interventions on covid-19 containment in taiwan. jama intern med. 2021;181(7):913-21. 53. du z, xu x, wang l, fox sj, cowling bj, galvani ap, et al. effects of proactive social distancing on covid19 outbreaks in 58 cities, china. emerg infect dis. 2020;26(9):2267. 54. islam n, sharp sj, chowell g, shabnam s, kawachi i, lacey b, et al. physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries. bmj. 2020;370. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 9 archives of academic emergency medicine. 2023; 11(1): e52 table 1: search strategy search terms 1. covid covid 19 or covid 19 or sars cov 2 or sars cov 2 or severe acute respiratory syndrome coronavirus 2 or ncov or 2019 ncov or coronavirus infections or coronavirus or coronavirus or coronaviruses or betacoronavirus or betacoronavirus or betacoronaviruses or wuhan coronavirus covid-19 pandemic or covid-2019 or 2019-ncov or betacoronavirus sars coronavirus2 sars cov or sars virus or sars virus or sars or sars2 or sars-2 or sars coronavirus 2 or sars-corona-virus2 2. non-pharmaceutical interventions social isolation or isolation strategy or isolation or patient isolation or patient isolation or patient isolators or patient isolators or cohorting or community containment or isolation strategy or isolation or home isolation or physical contact or physical distancing or quarantine or quarantines or quarantine or social distance or quarantines or quarantined or quarantining or social distance or social distancing or banning or distancing or contact tracing or contact investigation or contact screening school closures or workplace closure or university closure or university closures or travel restrictions or public events banned or event ban or gathering ban venue closure or border closure or lockdown or curfews or non-pharmaceutical interventions 3. reduce transmission reduce or reduced or reduces or transmission [mesh subheading] or transmission or transmissions or coronavirus infections/prevention and control [majr] or pandemics/prevention and control [majr] or prevention and control (mesh subheading) or prevention and control or prevention or reduce infection or coronavirus infections/prevention and control [majr] or pandemics/prevention and control [majr] 1 and 2 and 3 table 2: effects of social distancing interventions on covid-19 pandemic management intervention place impact of intervention south korea [35] rt reduction from 3.53 to 0.45 (february 18 to april 29) brazil [36] rt reduction from 1.76 to 0.71 in ceara area (march 14 to march 28) rt reduction from 1.45 to 0.87 in maranhão region (may 5 to may 19) from 0.87 to 0.5 (after 15 days) united states of america [37] 51% reduction in the number of new covid-19 cases ( january 22 to april 25) iran [38] 82% reduction in covid-19 cases (february 20 to may 13) 7% reduction in deaths (february 20 to may 13) social distancing united states [17] 0.9% reduction in daily covid-19 incidence (4 to 21 days after intervention) the united states and 134 other countries [18] 65% reduction in the spread rate of covid-19 cases (after 2 weeks) austria, belgium, italy, malaysia, and south korea [39] 52.37% reduction in growth rate of confirmed cases brazil [36] rt reduction from 1.76 to 0.71 in ceara area (march 14 to march 28) rt reduction from 1.45 to 0.87 in maranhão region (may 5 to may 19) from 0.87 to 0.5 (after 15 days) rt: rate of transmission this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index k. etemad et al. 10 table 3: impact of lockdown on covid-19 pandemic management intervention place impact of intervention 11 european countries [9] 81% reduction in rt australia [16] 50% reduction r0 india [40] reduction of r0 from 3.36 to 1.27 india [41] reduction of r0 from 2.38 to 2.04 with an average coverage of 18% of the intervention (march 25 to may 18) singapore [42] reduction of r0 from 1.03 to 0.85 with 100% coverage of the intervention (april 4 to april 14) delaware (united states) [22] reduction of cases from 11.71 to 4.72 mortality reduction from 0.75 to 0.31 hospitalization reduction from 1.5 to 1.24 (per 10,000 people) (march 24 to april 24) lockdown south africa [43] exposure rate reduced from 3.28% to 1.53% (april 1 to april 30) huangshi (china) [44] decrease in the number of cases from 103.9 to an average of 37 and the number of deaths from 51.1 to an average of 10.5 (after 3 weeks) south africa, germany, spain, italy, new zealand [45] reduction rate (per million) in south africa: from 3.7 to 1.7 germany: from 37.5 to 33.7 spain: from 176.3 to 82 italy: from 0.92 to 52.1 new zealand: from 7.5 to 1.7 united states of america [46] reduction of daily infection growth rate from 0.19 to -0.08 (standard linear regression coefficients) (march 19 to april 19) new york [26] decrease in the number of positive cases from 53.4% at the beginning of april to 4.7% by increasing the lockdown index (restriction of business activity and staying at home) spain [47] average percentage change in daily incidence, hospitalization cases, and icu hospitalization of -3.62, -6.2 and -8.83, respectively (march 15 to april 25) rt: rate of transmission; r0: reproductive number; icu: intensive care unit. table 4: effects of mixed interventions on covid-19 pandemic management impact of intervention place mix intervention 36% reduction in rt (from 1.7 before intervention to 1.1 after intervention) france [48] global quarantine, restriction of movement 96% decrease in rt (from 1.64 to 0.05) jilin (china) [49] comprehensive intervention measures, social distancing, rapid reaction by the prevention and control system, use of masks, travel ban, screening and isolation of outsiders 57% decrease in rt (2.53 to 1.07) japan [50] voluntary cancellation of events and gatherings, school closures 74% decrease in rt (2.68 to 0.7) thailand [51] social distancing, telecommuting, hand washing, face masks, quarantine 70.7% decrease in rt new york [11] school closures, voluntary or forced stay at home 38% reduction in r0 from 2.5 to 1.53 (april 20 to december 20, 2020) taiwan [52] case detection, contact tracing, 14-day quarantine reduction of cases to 82%, mortality to 100% hospitalization to 88% (april 20 to january 20) delaware (united states) [22] use of mask, contact tracing reduction of rt to less than 1 11 european countries [9] case-based isolation, encouragement of social distance, quarantine, closure of schools and universities, prohibition of public events 53.2% decrease in r0 from 0.71 to 0.33 ( january 17 to february 10) xi’an (china) [53] isolation of confirmed cases, cessation of public transport within the city, cessation of travel between cities, reporting of confirmed cases, quarantine, forced social distance88.6% decrease in r0 from 0.7 to 0.08 ( january 21 to february 14) nanjing (china) [53] overall reduction in the incidence of covid-19 by 13% data from 149 countries [54] school and workplaces closures, cessation of public transportation, restrictions on public gatherings and public events, restrictions on travel, social distancing rt: rate of transmission; r0: reproductive number; icu: intensive care unit. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index 11 archives of academic emergency medicine. 2023; 11(1): e52 figure 1: flow diagram for the selection process of identified articles. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/aaem/index introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e53 or i g i n a l re s e a rc h clinical manifestations and outcomes of colchicine poisoning cases; a cross sectional study mitra rahimi1, reza alizadeh2, hossein hassanian-moghaddam3,4, nasim zamani1,3, alireza kargar5, shahin shadnia1∗ 1. toxicological research center, excellence center of clinical toxicology, department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of internal medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. social determinants of health research center, shahid beheshti university of medical sciences, tehran, iran. 4. department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 5. student research committee, department of clinical pharmacy, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. received: january 2020; accepted: march 2020; published online: 17 april 2020 abstract: introduction: colchicine is a medication with narrow therapeutic index, leading to both accidental and suicidal poisonings incidents. this study aimed to investigate the clinical and laboratory manifestations, as well as outcomes of colchicine poisoning patients referred to emergency department. methods: in this retrospective cross sectional study, demographics, clinical features, laboratory parameters, and outcomes of colchicine poisoned patients who were admitted to an academic referral center, tehran, iran, during 7 years were extracted from the patients’ profiles and analyzed. results: 21 patients with the mean age of 25.48 ± 12.65 years were studied (61.9% female; 85.7% suicidal). the mean ingested colchicine dose was 30.25 ± 21.09 mg. the most common symptoms were nausea and vomiting observed in 19 (90.5%) cases, followed by abdominal pain in 10 (47.6%) and diarrhea in 9 (42.8%) cases. 3 (14.3%) had died, the cause being disseminated intravascular coagulation (dic) in two cases and severe metabolic acidosis in one. prevalence of abdominal tenderness (p = 0.001) and abdominal pain (p = 0.049) was significantly different between survived and non-survived patients. there were significant correlations between systolic blood pressure (p = 0.010), diastolic blood pressure (p = 0.002), serum glucose (p = 0.031), calcium (p = 0.017), white blood cell (wbc) count (p = 0.043), aspartate aminotransferase (ast) (p = 0.001), alkaline phosphatase (alp) (p = 0.012), prothrombin time (pt) (p = 0.006), partial thromboplastin time (ptt) (p = 0.014), paco2 (p = 0.011), dic (p < 0.001), and need for mechanical ventilation (p = 0.024) with survival. conclusion: based on the findings of the present study, the mortality rate of colchicine poisoning was 14.3% and there was significant correlation between lower blood pressure, lower serum glucose and calcium levels, lower paco2, higher wbc count, higher ast and alp levels, higher pt and ptt, need for mechanical ventilation, presence of dic, and also abdominal pain and tenderness with survival. keywords: colchicine; symptom assessment; toxicity; drug overdose; poisoning cite this article as: rahimi m, alizadeh r, hassanian-moghaddam h, zamani n, kargar a, shadnia sh. clinical manifestations and outcomes of colchicine poisoning cases; a cross sectional study. arch acad emerg med. 2020; 8(1): e53. 1. introduction colchicine is a medication extracted from plants including colchicum autumnale and gloriosa superba. it was first ∗corresponding author: shahin shadnia; toxicological research center, excellence center of clinical toxicology, department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. e-mail: shahin1380@gmail.com, tel/fax: +98-21-55424041 approved by the food and drug administration (fda) for the treatment of familial mediterranean fever (fmf), gout, amyloidosis, behcet’s syndrome, pericarditis, arthritis, pulmonary fibrosis, vasculitis, biliary cirrhosis, pseudogout, certain spondyloarthropathies, calcinosis, and scleroderma (1, 2). colchicine blocks cell mitosis in the metaphase, interferes with intracellular transport pathways by preventing polymerization of tubulin into microtubules, and is a competitive antagonist of gamma-aminobutyric acid (gaba) (2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rahimi et al. 2 the maximum recommended daily dose of this medication is 1.8 mg per day (3), while the overall cumulative dose in four days should not exceed 6 mg in adults and 3 mg in the elderly (4). colchicine is rapidly absorbed and dispersed, with serum amounts peaking at 0.5-2.0 hours following ingestion. several studies point out the fact that the therapeutic index of colchicine is narrow, and therefore, it is difficult to discriminate between nontoxic, toxic, and lethal doses. early identification of colchicine poisoning is crucial because sustained exposure may result in multi-organ failure and death (5). this study aimed to investigate the clinical and laboratory manifestations as well as outcomes of patients with colchicine poisoning referred to the emergency department. 2. methods 2.1. study design and setting in a retrospective study, all patients with colchicine poisoning who had been admitted to loghman-hakim hospital in tehran, iran, during 7 years (march 22, 2007, to march 21, 2014), were enrolled. the study protocol conforms to the ethical guidelines of the 1975 declaration of helsinki as reflected in a prior approval by the institution’s human research committee. our local ethics committee at shahid beheshti university of medical sciences approved the study. written informed consent was obtained from the patients for their anonymized information to be published in this article. 2.2. participants all hospitalized patients in toxicology ward or intensive care unit (icu) with colchicine poisoning, regardless of their age or sex, were included. we excluded all patients with coingestion. 2.3. data gathering a self-made questionnaire containing information on the patients’ demographic characteristics, the time elapsed between ingestion and hospital admission, clinical presentation on arrival, vital signs, laboratory data, duration of hospitalization, given treatment, and the final outcome was filled by a trained physician for every single patient. diagnosis of acute colchicine poisoning was based on the history given by the patients or their relatives, and laboratory findings. 2.4. statistical analysis data were analyzed using the social package for statistical analysis (spss) software version 20. the findings were presented as mean ± standard deviation for continuous variables and frequency (%) for categorical variables. chi-square and fisher’s exact tests were used to analyze categorical variables. statistical comparison was made using mann– whitney u-test for non-parametric variables and independent t-test for parametric variables. multivariate analysis was performed on demographics, vital signs on arrival, and laboratory panels to assess their correlation with patients’ survival. a p-value of 0.05 or less was considered to be statistically significant (two-tailed). 3. results 3.1. baseline characteristics of studied case 21 patients with the mean age of 25.48 ± 12.65 (range; 7 to 68) years were admitted with colchicine poisoning during the study period (61.9% female). 11 (52.4%) patients had underlying diseases, including familial mediterranean fever (fmf), hypothyroidism, gout, psychotic disorder, glucose-6-phosphate dehydrogenase (g6pd) deficiency, rheumatoid arthritis, and behcet’s disease. 18 (85.7%) had ingested colchicine to attempt suicide, and the other three (14.3%) had consumed it inadvertently. the mean ingested colchicine dose was 30.25 ± 21.09 mg. the most common symptoms were nausea and vomiting, observed in 19 (90.5%) cases, followed by abdominal pain in 10 (47.6%) and diarrhea in 9 (42.8%) cases. 3.2. outcomes the mean duration of of hospital stay was 3.64 ± 3.84 (range: 1 to 14) days. 9 (42.8%) cases were in need of intensive care unit (icu) admission (mean icu stay was 2.78 ± 1.98 days). 3 (14.3%) had died, and 18 (85.7%) had been discharged from the hospital without any complications. the three nonsurvivors had ingested 20, 38, and 40 mg of colchicine. cause of death was disseminated intravascular coagulation (dic) in two patients and severe metabolic acidosis in one. table 1 and figure 1 compare the baseline characteristics, clinical findings, and laboratory findings of patients between survived and non-survived groups. nausea and vomiting were present in all three patients who died. prevalence of abdominal tenderness (p = 0.001) and abdominal pain (p = 0.049) was significantly different between survived and non-survived cases. sinus tachycardia was present in four survivors and one non-survivor (p > 0.05). there were significant correlations between systolic blood pressures (p = 0.010), diastolic blood pressures (p = 0.002), serum glucose (p = 0.031), calcium (p = 0.017), white blood cell (wbc) count (p = 0.043), aspartate aminotransferase (ast) (p = 0.001), alkaline phosphatase (alp) (p = 0.012), prothrombin time (pt) (p = 0.006), partial thromboplastin time (ptt) (p = 0.014), paco2 (p = 0.011), dic (p < 0.001), and need for mechanical ventilation (p = 0.024) with survival. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e53 table 1: comparing the baseline characteristics, vital signs and laboratory findings of survivors and non-survivors variable survived (n = 18) died (n = 3) p value age (year) mean ± sd 26.11 ±12.75 21.67±13.87 0.690 sex male 7 (38.9) 1 (33.3) 0.858 female 11 (61.1) 2 (66.7) ingestion to hospital time (hours) mean ± sd 13.52 ± 17.09 8.50 ± 3.50 0.3 ingested colchicine dose (mg) mean ± sd 29.82 ± 22.63 32.67±11.01 0.473 hospitalization time (day) icu 0.9 ± 1.8 4 ± 1.7 0.008 toxicology ward 3.3 ± 2.1 0 0.006 total hospital stay 4±3.4 4±1.7 0.44 blood pressure (mmhg) sbp 116.94 ±13.41 93.33 ±7.63 0.010 dbp 76.67 ±10.43 46.67 ±27.53 0.002 laboratory findings serum glucose (mg/dl) 123.83 ± 71.26 69.67 ± 13.42 0.031 wbc (×109 /l) 9.07 ± 3.94 24.67 ± 6.09 0.043 calcium (mg/dl) 8.97 ± 0.83 7.53 ± 0.64 0.017 ast (u/l) 71.04 ± 82.94 357 ± 231.61 0.001 alp (u/l) 297.41 ± 233.01 1085.33 ± 650.42 0.012 pt (seconds) 14.47 ± 2.34 29.00 ± 4.24 0.006 ptt time (seconds) 28.92 ± 3.47 39.00 ± 6.55 0.014 need for mechanical ventilation number (%) 1 (5.5) 3 (100) 0.024 dic number (%) 0 (0) 2 (66.6) < 0.001 sd: standard deviation; icu: intensive care unit; sbp: systolic blood pressure; dbp: diastolic blood pressure; ast: aspartate aminotransferase; ptt: partial prothrombin time; pt: prothrombin time; alp: alkaline phosphatase; wbc: white blood count; dic: disseminated intravascular coagulation. table 2: comparing the clinical manifestations of survivors and non-survivors variable survived (n = 18) died (n = 3) p value nausea/vomiting 16 (88.89) 3 (100) 0.729 diarrhea 8 (44.44) 1 (33.33) 0.447 abdominal pain 2 (11.11) 3 (100) 0.049 abdominal tenderness 7 (38.89) 3 (100) 0.001 hyperactive bowel sound 1 (5.56) 0 (0.00) 0.8 headache 1 (5.56) 0 (0.00) 0.857 data are presented as number (%). 4. discussion based on the findings of present study, the mortality rate of colchicine poisoning was 14.3% and there was significant correlation between lower blood pressure, lower serum glucose and calcium levels, lower paco2, higher wbc count, higher ast and alp levels, higher pt and ptt, need for mechanical ventilation, presence of dic, and abdominal pain and tenderness with survival. most of our patients were young females. however, in previous studies, male patients were more commonly involved (6). the mortality rate was 14.3%, which is relatively low in comparison to lethal poisonings. ozdemir and colleagues had studied childhood poisoning in turkey and had stated that colchicine was the second leading cause of deadly poisonings after carbon monoxide when narcotics were excluded (7). our lowest lethal dose was 20 mg in an accidental intake in a 10-year-old boy with g6pd deficiency. other studies reported death due to ingestion of colchicine doses higher than 0.5 mg/kg and especially more than 0.8 mg/kg (8). although we found reports of complete recovery following consumpthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. rahimi et al. 4 tion of doses higher than 1 mg/kg (9), there were fatalities after the ingestion of doses as low as 0.5 mg/kg. starting treatment later than two hours after the ingestion of colchicine can therefore, significantly impair the course of therapy (10). in contrast to previous studies, in the present study surviving cases had taken longer to reach the hospital compared to non-survivors. the reason could be that some patients were referred to loghman hospital after their treatment had initiated in other hospitals. yet, the consumed amount of colchicine was significantly lower in survivors. we observed early-onset leukocytosis within 24-72 hours in non-survivors. according to erden et al., early onset of leukocytosis in the initial stages of colchicine poisoning is a useful factor to predict poor prognosis (10). in our study, non-survivors had higher values of liver enzymes, pt, ptt, wbc, and alp and decreased calcium, blood sugar, and paco2 levels. metabolic acidosis was also more prevalent in non-survivors compared to survivors, however the difference was not significant. all of the mentioned findings are consistent with the results of previous researches. appropriate and timely treatment can prevent death (11). in our study, injection of packed cells and fresh frozen plasma were needed in two patients with bone marrow suppression and dic who eventually died. however, it should be mentioned that we performed transfusion in another patient who ultimately survived. intravenous bicarbonate was indicated in two patients to correct metabolic acidosis, one of whom recovered, and the other died after going through progressive metabolic acidosis and emergent hemodialysis. the need for intubation was another poor prognostic factor in our cases. accidental colchicine poisoning may occur quite often. this poisoning is accompanied with a high mortality rate if it remains undiagnosed, and therefore, it should be suspected when clinical signs and symptoms imply the ingestion of an anti-mitotic medication. we observed that nausea and vomiting, abdominal pain, and abdominal tenderness, and dic were associated with poor prognosis. moreover, we revealed that systolic and diastolic blood pressures, serum glucose, calcium, and paco2 were significantly lower in nonsurvivors. besides, ast, alp, pt, and ptt measures were considerably higher in dead patients. intubation and mechanical ventilation significantly correlated with poor prognosis. supportive treatments are recommended to be initiated as soon as possible when indicated. 5. limitation since the study was retrospective, we could only review patients’ records, which could be considered as a limitation. also, it was not possible for us to confirm colchicine toxicity by analyzing its serum level. 6. conclusion based on the findings of present study, the mortality rate of colchicine poisoning was 14.3% and there was significant correlation between lower blood pressure, lower serum glucose and calcium levels, lower paco2, higher wbc count, higher ast and alp levels, higher pt and ptt, need for mechanical ventilation, presence of dic, and abdominal pain and tenderness with survival. 7. declarations 7.1. acknowledgements the authors express their sincere gratitude to the staff of the archiving unit of loghman hakim hospital for their assistance. 7.2. author contribution all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids mitra rahimi: 0000-0002-8785-8207 reza alizadeh: 0000-0002-1302-5966 hossein hassanian-moghaddam: 0000-0003-4370-0544 nasim zamani: 0000-0002-2091-0197 alireza kargar: 0000-0001-9582-8879 shahin shadnia: 0000-0002-9401-0781 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. santos cd, schier cjg. colchicine, podophyllin, and the vinca alkaloids. new york: mcgraw-hill; 2019. 11e. 2. baud fj, sabouraud a, vicaut e, taboulet p, lang j, bismuth c, et al. brief report: treatment of severe colchicine overdose with colchicine-specific fab fragments. new england journal of medicine. 1995;332(10):642-5. 3. rosenthal ak. treatment of calcium pyrophosphate crystal deposition (cppd) disease. uptodate inc.available from: http://www.uptodate.com. 4. aronson jk. meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions: elsevier; 2015. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e53 5. pettersen ja, singh a. potentially reversible rapid-onset weakness: recognizing colchicine toxicity. the american journal of medicine. 2018;131(2): e59-e60. 6. hassanian-moghaddam h, zamani n, rahimi m, shadnia s, pajoumand a, sarjami s.. acute adult and adolescent poisoning in tehran, iran; the epidemiologic trend between 2006 and 2011. archives of iranian medicine. 2014;17(8):534-8. 7. ozdemir r, bayrakci b, teksam o, yalcin b, kale g. thirty-three-year experience on childhood poisoning. the turkish journal of pediatrics. 2012;54(3):251-9. 8. bismuth c, baud f, dally s. standardized prognosis evaluation in acute toxicology its benefit in colchicine, paraquat and digitalis poisonings. journal de toxicologie clinique et experimentale. 1986;6(1):33-8. 9. iosfina i, lan j, chin c, werb r, levin a. massive colchicine overdose with recovery. case reports in nephrology and urology. 2012;2(1):20-4. 10. erden a, karagoz h, gumuscu hh, karahan s, basak m, aykas f, et al. colchicine intoxication: a report of two suicide cases. therapeutics and clinical risk management. 2013;9:505-9. 11. aghabiklooei a, zamani n, hassanian-moghaddam h, nasouhi s, mashayekhian m. acute colchicine overdose: report of three cases. reumatismo. 2014;65(6):307-11.. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 146 emergency (2015); 3 (4): 146-149 original research the effect of emergency department overcrowding on efficiency of emergency medicine residents’ education anita sabzghabaei, majid shojaee, hossein alimohammadi, hojjat derakhshanfar, parvin kashani, shohreh nassiriabrishamchi* department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: shohreh nassiriabrishamchi; department of emergency medicine, loghman hakim hospital, qazvin st, makhsus st, tehran, iran. tel: +982155419005; fax: +982155417547; email: khoshhal.kourosh@gmail.com received: december 2014; accepted: january 2015 abstract introduction: creating a calm and stress-free environment affects education significantly. the effects of the emergency department overcrowding (edo) on the training of emergency medicine residents (emr) is a highly debated subject. therefore, this study aimed to evaluate the effect of edo on efficiency of emr’s education. methods: in this cross-sectional study, the effects of overcrowding on emr’s education in the resuscitation room and acute care unit. data collection was done using a questionnaire, which was filled out by the second year emrs. the crowding level was calculated based on the national emergency department overcrowding scale (nedocs). the relationship between the two studied variables was evaluated using independent sample t-test and spss 21 statistical software. results: 130 questionnaires were filled out during 61 shifts. 47 (77.05%) shifts were overcrowded. the attend’s ability to teach was not affected by overcrowding in the resuscitation room (p=0.008). the similar results were seen regarding the attend’s training ability in the acute care unit. conclusion: it seems that the emergency department overcrowding has no effect on the quality of education to the emrs. key words: crowding; emergency department; education; resistance training cite this article as: sabzghabaei a, shojaee m, alimohammadi h, derakhshanfar h, kashani p, nassiriabrishamchi s. the effect of emergency department overcrowding on efficiency of emergency medicine residents’ education. emergency. 2015;3(4):1469. introduction: ducation is a series of purposeful activities planned by the educators, in the form of interaction between them and the learners (1, 2). education is one of the most important ways of ensuring the success of plans in all dimensions of the society. in addition, learning includes all the skills and knowledge gained by one, over the course of their life (3-6). eliminating confounding factors in education can increase the effectiveness of education (7-9). one of the major confounding factors in education is the educational environment (10). creating a calm and stress-free environment affects the training significantly. some studies believe that emergency department overcrowding (edo) can affect the training of emergency medicine residents (emr) while others do not (11-19). overcrowding can affect the interaction between the educator and learner (15). on one side, the excessive workload can create opportunities for learning and increase the efficiency of learning but on the other hand, less time is available for the interaction between the educator and the student (16). the effects of edo on the training of emrs is a highly debated subject. therefore, this study aimed to evaluate the effect of edo on the efficiency of emrs’ education. methods: study design and setting this cross-sectional study aimed to evaluate the effect of edo on the efficiency of emrs’ education. the study was carried out in 2013-2014 in shohadaye haftome tir hospital, tehran, iran. the protocol of study has been approved by the ethics committee of shahid beheshti university of medical sciences. the questionnaires were anonymous and the participants granted permission before the study. participants the participants were all second year emrs who were willing to take part in the study. the ability of the attend to teach the principles was evaluated in resuscitation room and the acute care unit. none of the residents evaluated an attend twice. data collection e this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 147 sabzeghaba et al data collection was done using a questionnaire, which was filled out by the second year residents. the residents evaluated her/his attends on the subject of teaching skills, creating a fear-free environment, willingness to teach, accessibility, level of busyness during the shift, number of visits/shift, interpersonal relationship skills, and their overall teaching scores. also both the resident and attend were asked about the crowding of the shifts. each question was given a score ranging from 1 to 10 (1 being the least and 10 the most possible score). in addition, the emergency crowding score was calculated based on the national emergency department overcrowding scale (nedocs). at the end of each 12-hour shift using nedocs the department’s crowding was evaluated. if the score was less than 100, the department was considered not overcrowded and if it was higher than 100, the shift was considered overcrowded. the reliability of the questionnaire was approved by 2 emergency medicine specialists and 1 epidemiologist. the validity of the questionnaire was confirmed by calculating kronbach’s alpha (0.79). statistical analysis the appropriate sample size for this study was 130, which was calculated by considering the standard deviation of 1 not overcrowded and 1.5 in overcrowded hours (20), power of 90%, confidence level of 95% (α=0.05), and error of 0.5. the data were analyzed using spss 21. the results were given as means and standard deviations. the relationship between the department overcrowding and the quality of education was evaluated using independent sample t-test. in all the analyses p<0.05 was considered as significance level. results: 130 questionnaires were filled out during 61 shifts (26 night shifts and 35 day shifts, 27 residents evaluated 8 attends). 47 (77.05%) shifts were overcrowded. the attend’s ability to teach was not affected by overcrowding in the resuscitation room. in the overcrowded shifts the number of visits done by the attend were significantly higher (p=0.008) (table 1). it is notable that similar results were seen regarding the attend’s training ability in the acute care unit (table 2). also in this unit, the number of visits done by the attend were significantly higher in the overcrowded shifts (p=0.03). discussion: the results of this study showed that from the emrs’ point of view, the attends achieve the highest scores in creating a fear-free environment, interpersonal relationship skills, accessibility and teaching skills during edo. it is worth noting that the total teaching score achieved by the attends was 6.8 (out of 10) in the resuscitation room and 6.5 (out of 10) in the acute care unit. it was also demonstrated that edo has no effect on the attends’ teaching skills and abilities. some researchers believe that emergency department overcrowding can negatively affect emergency residents’ training and learning (14-19). in contrast to the results of the present study, skeff et al. express in their study that job stress has a negative impact on education (21). also atzema et al. propose in their review study that overcrowding might affect the interaction between the educator and the student as this interaction needs a calm environment for asking questions, concentrating on the educator’s training and reaching a conclusion regarding the educator’s instructions. these principles might be affected by the department overcrowding. these researchers express that the department overcrowding is an important factor causing time limitations for training. also excessive workload and the need to take care of and treat the patients leaves little time table 1: the mean score regarding the evaluated factors in the resuscitation room based on the department’s crowding evaluated factor nedosc total score p < 100 > 100 creating a fear-free environment 8.4 ± 1.4 8.7 ± 1.3 8.6 (1.3) 0.83 teaching skills 6.6 ± 2.4 7.1 ± 2.4 6.8 (2.4) 0.36 willingness to teach 5.6 ± 2.9 6.8 ± 2.3 6.2 (2.65) 0.07 accessibility 6.5 ± 2.8 7.5 ± 2.2 7.0 (2.5) 0.13 interpersonal relationship skills 8,0 ± 1.7 8.3 ± 2.9 8.2 (2.0) 0.59 overall teaching score 6.3 ± 2.2 7.2 ± 2.1 6.8 (2.15) 0.11 level of busyness during the shift 5.2 ± 2.6 6.8 ± 2.7 6.1 (2.8) 0.02 number of visits/shift 4.0 ± 2.5 5.7 ± 2.6 5.2 (2.5) 0.008 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (4): 146-149 148 for the attends to ask the residents questions and wait for their answers (14). however, the results from the present study showed that overcrowding did not affect the attends’ education score. this disagreement in the results can have 2 reasons. firstly, as can be seen, the studied emergency departments are crowded most of the time and therefore the constant crowding can result in the emergency medicine attends being adapted to these situations and having their skills developed so that they can give the necessary education in little time. secondly, the attends who have participated in this study have had relatively high interpersonal relationship skills (a score of 8.2 out of 10). therefore, the interaction between the residents and the attends has been more affected by this factor rather than the edo. but in line with the results of this study, mahler et al. determined that no significant difference exists between the residents’ perceptions regarding the educational value in the overcrowded and non-overcrowded times (22). these researchers express that in the overcrowding period, the residents do less visits and treatment processes while the attends are busier. therefore, it is possible that the residents have more time to learn, study and observe the correct treatment processes done by the attend. the emergency department overcrowding gives the residents the opportunity to observe various clinical cases and directly observe the correct ways of managing and treating the patients because at the times of overcrowding, the attends do more visits. therefore, we can say that the edo possibly not only doesn’t impact the attends’ presented education negatively, but also can result in an increase in the efficiency of the education. this mostly depends on the attends’ educating skills. we should not leave out the educational principles of the health system. the principles of the educational system, including the points of view, beliefs, schedules, and regulations can all affect the teaching methods. rigid and inflexible regulations and nonprofessional decisions, and the educational system being in line with the students’ needs or not can all affect education (3, 10, 23). conclusion: based on the results of the present study, edo has no effect on the educational skills and abilities of the attends. they achieve the highest scores in creating a fear-free environment, interpersonal relationship skills, accessibility and teaching skills in both overcrowded and non-overcrowded situations. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of shohadaye haftome tir hospital, tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. biggs j, tang c. teaching for quality learning at university: mcgraw-hill international; 2011. 23-7 p. 2. heydari gr, ramezankhani a, hosseini m, yousefifard m, masjedi mr. evaluation of knowledge, attitude and practice about smoking among male teachers in tehran, iran. payesh. 2010;10(4):355-61. [in persian]. 3. bishop k, denley p. learning science teaching: mcgraw-hill international; 2007. 33-5 p. 4. hosseini m, bekry g, mozaffari hr, et al. effect of educational intervention on oral health behaviour based on health belief model in female secondary school students of paveh in 2011. ed res med sci j. 2014;2(3):2-9. 5. kariman h, joorabian j, shahrami a, alimohammadi h, noori z, safari s. accuracy of emergency severity index of triage in imam hossein hospital-tehran, iran (2011). j gorgan uni med sci. 2013;15(1):115-20. [in persian]. 6. baratloo a, maleki m. description of a working day as a senior emergency medicine resident; burning candle at both ends! emergency. 2015;3(1):pp. 1. 7. nath b, kumari r, kamboj n. national social service scheme: integration in medical education. ind j commun health. 2014;26(1):1-2. 8. mann kv. theoretical perspectives in medical education: past experience and future possibilities. med educ. 2011;45(1):60-8. table 2: the mean score regarding the evaluated factors in the acute care unit based on the department’s crowding evaluated factor nedosc total score p < 100 > 100 creating a fear-free environment 8.4 ± 1.8 8.3 ± 2.0 8.4 (1.9) 0.76 teaching skills 6.8 ± 2.5 6.5 ± 2.0 6.7 (2.2) 0.59 willingness to teach 5.5 ± 2.9 5.8 ± 2.4 5.7 (2.7) 0.6 accessibility 6.9 ± 2.9 6.7 ± 2.7 6.3 (2.8) 0.24 interpersonal relationship skills 8.2 ± 2.0 7.8 ± 1.9 7.95 (1.0) 0.36 overall teaching score 5.9 ± 2.5 6.9 ± 2.0 6.5 (2.3) 0.09 level of busyness during the shift 5.1 ± 2.8 6.1 ± 2.9 5.8 (2.9) 0.19 number of visits/shift 4.0 ± 2.6 5.4 ± 2.1 4.9 (2.3) 0.03 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 149 sabzeghaba et al 9. baratloo a, maleki m. iranian emergency department overcrowding. journal of emergency practice and trauma. 2015;1(2). 10. van dinther m, dochy f, segers m. factors affecting students’ self-efficacy in higher education. educ res revi. 2011;6(2):95-108. 11. pines jm, hilton ja, weber ej, et al. international perspectives on emergency department crowding. acad emerg med. 2011;18(12):1358-70. 12. esmaeilpour m, salsali m, ahmadi f. workplace violence against iranian nurses working in emergency departments. int nurs rev. 2011;58(1):130-7. 13. smith jp, shokoohi h, holliman jc. the search for common ground: developing emergency medicine in iran. acad emerg med. 2007;14(5):457-62. 14. atzema c, bandiera g, schull mj, coon tp, milling jr tj. emergency department crowding: the effect on resident education. ann emerg med. 2005;45(3):276-81. 15. sabbah s. the impact of hospital overcrowding on postgraduate education: an emergency medicine resident’s perspective through the lens of canmeds. cjem. 2009;11(3):247-9. 16. warden g, griffin r, erickson s, et al. hospital-based emergency care: at the breaking point. washington, dc, usa: national academies press; 2006. 65 p. 17. schull mj, slaughter pm, redelmeier d. urban emergency department overcrowding: defining the problem and eliminating misconceptions. can j emerg med. 2002;4(2):7683. 18. weiss sj, derlet r, arndahl j, et al. estimating the degree of emergency department overcrowding in academic medical centers: results of the national ed overcrowding study (nedocs). acad emerg med. 2004;11(1):38-50. 19. aldeen az, gisondi ma. bedside teaching in the emergency department. acad emerg med. 2006;13(8):860-6. 20. pines jm, prabhu a, mccusker cm, hollander je. the effect of ed crowding on education. am j emerg med. 2010;28(2):217-20. 21. skeff km, bowen jl, irby dm. protecting time for teaching in the ambulatory care setting. acad med. 1997;72(8):694-7. 22. mahler sa, mccartney jr, swoboda tk, yorek l, arnold tc. the impact of emergency department overcrowding on resident education. j emerg med. 2012;42(1):69-73. 23. mccoy s, emer s. higher education expansion and differentiation in the republic of ireland. high educ. 2011;61(3):243-60. introduction: methods: study design and setting participants data collection statistical analysis results: discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 50 emergency (2015); 3 (2): 50-53 original research erythrocyte sedimentation rate measurement using as a rapid alternative to the westergren method reza hashemi1, alireza majidi2*, hassan motamed3, afshin amini4, fares najari5, ali tabatabaey2 1. department of internal medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran. 4. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 5. department of forensic medicine, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: alireza majidi, department of emergency medicine, shahid beheshti university of medical sciences, shohadaye tajrish medical center, tajrish square, tehran, iran. tel: +982122721155; fax: +982122721155; email: pezeshkmajidy@yahoo.com received: september 2014; accepted: november 2014 abstract introduction: erythrocyte sedimentation rate (esr) remains as one of the most reliable tests in clinical practices. yet its use is time consuming and requires a large blood sample. the aim of this study was assessing a faster and reliable method of esr estimation. methods: an esr estimation method was described and performed on 108 patients using capillary tube (micro esr) and capillary peripheral blood. micro esr results at different intervals were measured and compared with westergren esr (conventional esr) estimation by pearson and spearman’s coefficients. a regression equation was derived to predict conventional esr values based on micro esr results. the agreement of two measurements was demonstrated using the bland-altman plot. results: micro esr results at 20 minutes showed the earliest close correlation with conventional esr results at one hour (r = 0.987). the presented regression equation was able to closely predict esr values (r2 = 0.974) and the bland-altman plot showed an acceptable agreement between converted and conventional esr measurements. conclusion: using capillary tube and capillary blood sample (micro esr) appears to be a faster, cheaper, more reliable, and precise tool for esr measurement in the ed. the results have acceptable correlation with conventional esr, especially at 20 minutes of measurement. key words: blood sedimentation; methods; erythrocytes; capillary tubing; emergency medicine cite this article as: hashemi r, majidi a, motamed h, tabatabaey a. erythrocyte sedimentation rate measurement using as a rapid alternative to the westergren method. emergency. 2015;3(2):50-3. introduction: rythrocyte sedimentation rate (esr) is one of the most commonly requested laboratory tests prescribed by physicians (1). its rate is dependent on various physiologic and pathologic factors including hemoglobin concentration, ratio of plasma proteins, serum lipid concentration, and plasma ph (2). this limitation has not yet reduced the use of this test in different clinical settings. it is still often used to indicate disease severity and disease dynamic. in the emergency department (ed), esr determination is an important part of critical and emergent diagnoses such as giant cell arteritis (gca) and takes as an essential base for patient disposition in those with rheumatologic conditions (3). furthermore, the role of esr in clinical decision-making of non-emergent conditions has been reestablished in different settings including rheumatologic, hematologic, and even orthopedics (4-7). although fahraeus and westergren are often credited for the introduction of esr and its clinical implications (8, 9), the test was originally described by biernacki in poland about a couple of decades before (10). it calculates the rate of sedimentation for red blood cells (rbc) within a 200 mm vertical tube of anticoagulated blood. blood containing an anticoagulant remains as suspension for a relatively long time due to negative electrical charges on rbc surfaces (11). the process of erythrocyte sedimentation is described in three phases: aggregation, precipitation, and packing; aggregation is the most influential phase in determining the outcome of the test (12). there are two main factors, which may influence the aggregation process: high moe this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 51 emergency (2015); 3 (2): 50-53 lecular weight components of the plasma and rbc structure. normally, rbcs have negative charges and repel each other; while, many plasma proteins have positive charges and neutralize the surface charges of erythrocytes, which promote the aggregation. therefore, an increase in plasma proteins will be associated with higher esr. the relative contribution of plasma proteins to aggregation on a scale of 10 is 10 for fibrinogen, five for beta-globulin, 2 for alpha-globulin, 2 for gamma-globulin, and 1 for albumin. on the other hand, esr is directly proportionate to the mass of erythrocyte, but inversely related to the area of its surface. macrocytes sediment more rapidly than normal cells and microcytes (11). the westergren method for esr estimation is simple and relatively cheap, but time-consuming and requires a relatively large volume of blood (12). newer versions of esr estimation have been proposed throughout the years and aimed to reduce its shortcomings while keeping its benefits (2, 13, 14). one of these flaws, especially in the emergency setting, is that the test requires at least 60 minutes, before it can be reported. an alternative method of esr estimation, which has been first described by stuart et al. (1974), is micro-esr method, which uses capillary tube and capillary blood sample. it is observed that despite its shorter time requirement and no need for venipuncture, the results of this method are closely correlated with that of westergren esr. however, this method is not a routinely used in the ed. therefore, the present study aimed to assess the validity of this old method for applying in emergency settings. methods: study design and setting this was a cross-sectional study of patients’ required esr analysis at shohadaye tajrish hospital, tehran, iran. all patients requiring esr evaluation, according to treating physician’s order, were included. in a one-month period, 108 patients were studied. all patients were asked to give an informed verbal consent. the study design was approved by the ethical committee of shahid beheshti university of medical sciences. procedure for all participants esr measuring was performed using both micro (capillary tube) and conventional (westergren) methods, simultaneously (8). micro method was performed by the same researcher for all patients, while conventional method was conducted by laboratory technicians. the two sides were blinded to the result of the alternative technique. since one of the study goals was finding the shortest time that has acceptable correlation with the findings of conventional method after 60 minutes, micro esr results were documented at 10, 15, 20, 25, 30, 40, 50, and 60 minutes. in conventional method, at the time of sampling, 1.6 cc of patient’s whole blood was gently mixed with 0.4 cc of 3.8% sodium citrate. then the anticoagulated blood was sucked into a glass westergre n pipette, placed into a stand, and fixed in vertical position for one hour. the sedimentation rate was estimated by measuring the column of serum at the top of the tube, based on millimeter per hour. the required equipment for micro technique is listed in table1. first, a drop of sodium citrate was put on a clean slide using a dropper. the patient’s fingertip was cleaned with an antiseptic agent; and punched using a lancet. the fingertip was held over the slide until four drops of blood were collected. care was taken in not touching the slide with the finger so that full drops were collected and the 4:1 ratio between blood and sodium citrate was maintained. in case of failing to provide 4 drops, the finger was milked distally until the desired numbers of drops were collected. the collected blood was then gently mixed with the citrate on the slide using a plastic probe. then a 7.5-centimeter capillary tube was placed on the slide immediately with a 30 to 45 degree angle. the tubes used, were heparin-free micro hematocrit tubes with an internal diameter of 1.2 millimeter (15, 16). the blood then rose into the tube due to capillary rise properties. if this fails to occur, the tube should be further lowered to smaller angle, while care should be taken to prevent entering air bobbles to the tube. after 7 centim eter rising in the tube, a finger was placed over the top end of the capillary tube to prevent further rise. the tube was then repositioned perpendicularly a nd placed into a standard micro-hematocrit seal paste in order to hold the tube in the desired vert ical position. burying 3 to 4 millimeter of the capillary bottom of the tube into the paste causes a further 1 to 2 millimeter rise in the column of blood. this was utter importa nce that the blood did not overflow. the tube should be fixed in a 90-degree angle to the surface, away from any vibrations. the level of blood was marked on the tube and then the rate of sedimentation within the tube documented at previously determined intervals, based on millimeter per hour. statistical analysis table 1: required equipment for capillary tube method of esr measurement (micro esr) lancet sodium citrate dropper laboratory slide micro hematocrit capillary tubes antiseptic solution special rack with paste to hold capillary tubes in place ruler stopwatch this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hashemi et al 52 the data were analyzed using spss version 21.0 software. the correlation between micro esr rates at different intervals (at 10, 15, 20, 25, 30, 40, 50, and 60 minutes) were compared with results of conventional method, as the gold standard, with pearson and spearman correlation method. a regression model was applied to calculate a formula for the conversion of the result of micro esr values at the time of best correlation with conventional method. the micro esr values were converted through this formula and then checked for having agreement with the gold standard using a blandaltman plot. in order to compare the variations between results, the coefficient of variation was calculated in both methods. results: overall, 108 patients were included (56.2% male). patients had age range from 18 to 89 years. the earliest significant correlation was seen at 20 minutes with a remarkable correlation by pearson’s method (r = 0.987, p < 0.001). figure 1 shows the scatter plot of micro esr values at 20 minutes and corresponding conventional esr values. since micro esr and conventional esr have different ranges of results, a regression equation was derived to predict conventional esr values from micro esr values at 20 minutes as follows: conventional esr values = 2.819 × micro esr values at 20 minutes + 1.346 (r2 = 0.974). the bland-altman plot shows the agreement rate of converted results with conventional esr values. this plot showed an acceptable agreement between the two values. it also showed better agreement at lower values of esr (figure 2). the coefficient of variation for conventional esr and converted micro esr results were 80% and 79%, respectively. figure 1: scatter plot of the result of micro esr and conventional methods at 1 hour (p < 0.001). esr: erythrocyte sedimentation rate; ct-esr 20 min: the value of esr in 20 minutes in capillary tube method esr measurement (micro esr). figure 2: bland-altman plot for assessment of agreement rate between the mean measurements of conventional esr and converted micro esr at different esr values. discussion: the study results showed that micro esr at 20 minutes had the earliest significant correlation with conventional esr, which means that micro esr results can be successfully interpreted after this time; thus, it can reduce the report time to a third of that in conventional esr method. furthermore, it was shown that accurate estimations of the conventional esr could be made through correcting micro esr measurements at 20 minutes by a simple formula presented here. this is helpful in situations where the clinician makes a decision based on previous measurements of recognized quantitative esr. the correlation seen between the results of micro esr and conventional esr was proved excellent in this group of patients. esr determination is one of the most basic tests performed in diagnostic laboratories. its result has great importance for some critical diagnoses such as giant cell arteritis in the ed. it also takes as an important index in the management and disposition of patients with rheumatologic conditions as well as integral part of clinical decision-making for a wide range of medical conditions. however, the conventional method of westergren, suggested by the international committee for standardization in hematology as the standard procedure (17), is time consuming and requires a relatively large volume of patient’s blood. this is especially cumbersome for critically ill patients requiring multiple samplings, infants, and neonates. it has been suggested that removal of 1 milliliter of blood from a 1,000 gram infant is estimated to be equivalent to removing 70 milliliter from the average adult (13). therefore, a faster but reliable test can greatly help in timely clinical decision making, while a simpler method of sample collection will be welcomed by both patients and clinicians. the conventional esr method requires at least 1 hour of sedimentation. here, we assessed a faster method of estimating esr by means of capillary tubes and peripheral capillary blood. this 0 10 20 30 40 0 20 40 60 80 100 120 ct-esr 20min c o n v e n ti o n a l e s r micro esr measures 0 20 40 60 80 100 120 140 -20 -15 -10 -5 0 5 10 15 20 mean of conventional esr and correction c o n v e n ti o n a l e s r c o rr e c ti o n mean -0.0 -1.96 sd -8.4 +1.96 sd 8.4 mean of measurements with two methods d if fe re n ce o f m e a su re m e n ts b e tw e e n t w o m e th o d s this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 53 emergency (2015); 3 (2): 50-53 was not the first time capillary blood and micro tubes used for the esr estimation (18, 19); but, to our knowledge, this was the first time that such a small sample of capillary blood was applied. when the results were converted by the formula presented here, the results displayed a close agreement with that of conventional esr. it seems that performing esr using capillary tubes and capillary blood may be a reliable substitute for conventional esr measurement. furthermore, alongside its time saving and diagnostic accuracy, the method described here does not require venipuncture, requires less blood, less sophisticated equipment, and is more economical. all of these features in different parts such as screening, diagnosis, and follow up of the disease turn it to a more desirable and cost-effective alternative to the conventional method proposed by westergren. larger studies with wider range of patients will be required in the future to reaffirm the finding of this study. limitations although this study reveals a significant correlation between the proposed method and conventional esr, its limitations should be taken into consideration. no strict inclusion or exclusion criteria were implemented here. in other words, no effort was made to gather abnormal results. therefore, the majority of results were in normal limitations and fewer data in the extremes (where greater discrepancy might be expected) were available. moreover, the new method of micro esr is carried out only once on each patient and therefore the reproducibility of the results is not clear. nevertheless, the impressive correlation and agreement of micro esr with conventional esr in a wide range of patients paves the way for assessment of its reproducibility and validity in extreme outcome of future studies. conclusion: using capillary tube and capillary blood sample (micro esr) appears to be a faster, cheaper, more reliable, and precise tool for esr measurement in the ed. the results have acceptable correlation with conventional esr, especially at 20 minutes of measurement. acknowledgments: we would like to acknowledge all the staff of emergency ward and laboratory unit of shohadaye tajrish hospital, tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors met four recommended criteria of authorship released by international committee of medical journal editors (icmje). references: 1. thue g, sandberg s. survey of office laboratory tests in general practice. scand j prim health care. 1994;12(2):77-83. 2. pawlotsky y, goasguen j, guggenbuhl p, et al. sigma esr: an erythrocyte sedimentation rate adjusted for the hematocrit and hemoglobin concentration. am j clin pathol. 2004;122(5):802-10. 3. kermani ta, schmidt j, crowson cs, et al. utility of erythrocyte sedimentation rate and c-reactive protein for the diagnosis of giant cell arteritis. semin arthritis rheum. 2012;41(6):866-71. 4. cheung r, sillence do, tchan mc. homocysteine and erythrocyte sedimentation rate correlate with cerebrovascular disease in fabry disease. jimd rep. 2012;6:101-5. 5. choi y, park b, kim k, et al. erythrocyte sedimentation rate and anaemia are independent predictors of survival in patients with clear cell renal cell carcinoma. br j cancer. 2013;108(2):387-94. 6. stojan g, fang h, magder l, petri m. erythrocyte sedimentation rate is a predictor of renal and overall sle disease activity. lupus. 2013;22(8):827-34. 7. tamhane a, redden dt, mcgwin g, jr., et al. comparison of the disease activity score using erythrocyte sedimentation rate and c-reactive protein in african americans with rheumatoid arthritis. j rheumatol. 2013. 8. westergren a. the technique of the red cell sedimentation reaction. am rev tuberc. 1926;14:94-101. 9. westergren a. diagnostic tests: the erythrocyte sedimentation rate range and limitations of the technique. triangle. 1957;3(1):20-5. 10. biernacki e. samoistna sedymentacja krwi jako naukowa, praktyczno-kliniczna metoda badania. gazeta lekarska. 1897;17:962-96. 11. sox hc, jr., liang mh. the erythrocyte sedimentation rate. guidelines for rational use. ann intern med. 1986;104(4):51523. 12. zhao tx, lockner d. electrical impedance and erythrocyte sedimentation rate (esr) of blood. biochim biophys acta. 1993;1153(2):243-8. 13. atas a, cakmak a, soran m, karazeybek h. comparative study between the ves-matic and microerythrocyte sedimentation rate method. j clin lab anal. 2008;22(1):70-2. 14. bull bs, brailsford jd. the zeta sedimentation ratio. blood. 1972;40(4):550-9. 15. sabine jc, nickolai dj. a microhematocrit method and its use with citrated blood. blood. 1952;7(11):1128-31. 16. wongkrajang p, opartkiattikul n, chinswangwatanakul w, areewatana s. accuracy and precision evaluation of thai plastic microhematocrit tubes: the first product from thailand. j med assoc thai. 2012;95(6):809-15. 17. icsh recommendations for measurement of erythrocyte sedimentation rate. international council for standardization in haematology (expert panel on blood rheology). j clin pathol. 1993;46(3):198-203. 18. parida sn, verma ic, singh mb, thomas s. evaluation of micro erythrocyte sedimentation rate in the diagnosis of neonatal sepsis. indian j pediatr. 1980;47(388):381-4. 19. douglas se, randolph tr. development of a micro-esr system with potential for in-home use. clin lab sci. 2007;20(1):12-9. march 17, 2020 total lab-confirmed cases: 16,169 total associated deaths: 988 total recovered cases: 5,389 new cases: 1,178 national covid-19 campign the main strategy of the ministry of health (moh) for the control of covid-19 is active case finding using electronic tools, taking advantage of the capacity of the national primary health care (phc) network, and community engagement. to accomplish this, all people are asked to participate in the screening process using the moh's self-assessment portal (salamat.gov.ir). health workers and public volunteers actively contact suspected cases using information recorded in this portal, as well as the electronic health record (sib portal). they actively evaluate individuals, follow-up them, and provide them with necessary information. where needed, clients are referred to 16-hour treatment clinics, which are specifically set up for the diagnosis and treatment of the disease, to the hospitals, or will be treated at home. the preliminary results of this national campaign (launched nationwide last week) is provided in this factsheet. results of of covid-19 active evaluation in the sib portal & selfassessment in salamat portal of 15 milion screened individuals, 35% are registered in salamat portal and 65% are registered in sib portal result of the 16-h clinics only 5% of clients referring to 16-h clinics are referred to hospitals by the healthcare providers. about 94% of these clients are apprently healthy without covid-19 symptoms, or are recmmended to stay at home by the general practiotioner of the 16-h clinic. the graph shows daily increase in the number of individuals visiting the screening portals for the assessment of covid-19 symptoms. screening rate of covid-19 (by location) there is diversity in the proportion of individuals screened for covid-19. registration rate in salamat portal (by location) there is diversity in the registration in salamat portal in different localities. source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran active evaluation of covid-19 in the sib portal 65% selfassessment of covid-19 in salamat portal 35% apparently no symptoms 66% needs homecare 29% outpatient (dual-drug regimen) 1% needs referral to the hospital 4% 32 9,061 1,670 63,264 153,352 408,511 615,265 780,669 1,043,818 883,043 1,791,972 2,648,642 4,008,220 0 1,000,000 2,000,000 3,000,000 4,000,000 5,000,000 5-mar 6-mar 7-mar 8-mar 9-mar 10-mar 11-mar 12-mar 13-mar 14-mar 15-mar 16-mar 17-mar n u m b e r number of individuals screened for covid-19 per day archives of academic emergency medicine. 2020; 8(1): e11 or i g i n a l re s e a rc h knowledge, attitude, and practice of emergency medical services staff in bleeding control of trauma patients; a cross sectional study yaser sharifi1 malahat nikravan mofard2∗, maryam jamsahar2, malihe nasiri2, mehdi safari2 1. student research committee, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. department of medical surgical nursing, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. received: november 2019; accepted: december 2019; published online: 26 january 2020 abstract: introduction: external hemorrhage is a leading cause of preventable death due to trauma and emergency medical services (ems) staff members play a vital role in the frontline of trauma management. this study aimed to assess the knowledge, attitude and practice of ems staff in bleeding control. methods: this knowledge, attitude and practice (kap) study was conducted to assess the educational needs of ems staff of hormozgan province, iran, regarding the bleeding control of trauma patients, during 2019. the participants were randomly selected and then their knowledge, attitude, and practice in management of hemorrhage and hemorrhagic shock were assessed using two researcher-made scenario-based questionnaires and one checklist. results: the scores for knowledge of the ems staff regarding actions during complete amputation, status of injured patients, and medical measures during transfer of injured patients were 3.22 ± 0.68, 2.28 ± 0.83, and 2.29 ± 0.62, respectively. the average participants’ attitude scores regarding the fear of bleeding, the importance of bleeding control, and confidence in bleeding control were 2.09±0.56, 2.4±0.58, and 1.76±0.55, respectively. the findings indicated that mean practice score was 1.72 ± 0.46 in capillary hemorrhage control, 1.41 ± 0.25 in venous bleeding control, 1.47 ± 0.25 in arterial bleeding control, and 1.56±0.27 in control of bleeding in the amputee limb. conclusion: the knowledge, attitude, and practice of ems staff regarding bleeding control were moderate, positive and appropriate, and incomplete, respectively. since bleeding is a life threatening status and ems staff skills are critical in this issue, it seems that we need to provide continuous education in this regard. keywords: hemorrhage; advanced trauma life support care; wounds and injuries; health knowledge, attitudes, practice cite this article as: sharifi y, nikravan mofard m, jamsahar m, nasiri m, safari m. knowledge, attitude, and practice of emergency medical services staff in bleeding control of trauma patients; a cross sectional study. arch acad emerg med. 2020; 8(1): e11. 1. introduction road traffic deaths are expected to increase to 2 million per year by 2020, which will mostly occur in developing countries, especially in south asian countries (1). acute, lifethreatening hemorrhage after trauma is a major cause of early mortality after trauma, accounting for 40% of trauma deaths globally (2, 3). managing a multiple trauma patient in the presence of severe hemorrhagic shock is naturally a challenge (4). although active bleeding in the organs or local bleeding may be tem∗corresponding author: malahat nikravan mofard, department of medical surgical nursing, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. tel: 00989027180330, email: m.nikravan@sbmu.ac.ir porarily controlled by manual pressure or using a tourniquet, an urgent intervention is needed to stop uncontrolled bleeding (5). traumatic hemorrhagic shock is associated with a high rate of mortality, depending on the duration and extent of reduction in tissue perfusion, most of which occurs in prehospital settings (8); and in severe trauma management, the aim of emergency medical services (ems) is to reduce the time between an injury and definitive medical care. ems staff act as a bridge between the community and medical services. the ems is first department in healthcare systems which mainly deal with emergency patients, and the more appropriate, accurate, and faster the services become, the lower the number of deaths and mortality rate and people’s confidence to ems will be increased. in iran, ems, as an essential element in treatment of emergency patients in the pre-hospital setting, plays a decisive role in reducing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem y. sharifi et al. 2 mortality and improving patients’ outcome (6). out of the 31,058 pre-hospital missions accomplished in 2017 in hormozgan province, iran, 13,103 were related to road accidents and traumas (7). to increase the chance of a patient’s survival, several national agencies, including the american surgeons committee on trauma, have attempted to highlight the importance of rapid response to hemorrhage (9). although the management of bleeding slightly varies between different systems, the overall methods are similar and are in accordance with the general principles of advanced trauma life support (atls) protocol (10). identifying the strengths and weaknesses of ems staff in this regard, and improving the quality of their approach is very important (11). therefore, this study aimed to evaluate the knowledge, attitude and practice of ems staff in bleeding control of trauma patients. 2. methods 2.1. study design and setting this knowledge, attitude and practice (kap) study was conducted during a 1-year period in 2019 to assess the educational needs of ems staff of hormozgan province, iran, regarding bleeding control of trauma patients. the participants were selected from ems staff of the province and then their knowledge, attitude, and practice in management of hemorrhage and hemorrhagic shock were assessed using two scenario-based questionnaires and one checklist. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences, iran, receiving the ethical code ir.sbmu.pharmacy.rec.1398.27. 2.2. participants all pre-hospital emergency staff members working in the ems stations of hormozgan province were selected using census sampling method. having at least an associate degree in medical emergencies or a bachelor’s degree in nursing, and experience of working in the pre-hospital emergency unit were among the inclusion criteria. the staff members working in the administrative unit of pre-hospital emergency or the dispatch unit were excluded. 2.3. data gathering the data collection tools developed by the research team included a demographic survey, two scenario-based questionnaires for assessing the knowledge (appendix 1) and attitude, and one checklist for evaluating the practice of ems staff regarding bleeding control in trauma patients. questionnaires were given to ten experts to assess their face and content validity, which were confirmed after making modifications. to assess the reliability of the questionnaires, they were reevaluated by 10 experts after a week. the intra-class correlation coefficient (icc) was 0.9. also, the reliability of the checklists was assessed using inter-rater agreement coefficient (0.85). a demographic survey consisting of 8 items based on personal information and work experience of ems personnel in the pre-hospital setting was used to gather the data of the participants. the data were collected by an emergency nurse with a master’s degree. in order to collect data, the researcher referred to the pre-hospital emergency units of hormozgan province. the researcher visited pre-hospital emergency services in hormozgan, and following coordination with authorities and obtaining consent from the pre-hospital staff members, first, the demographic survey and the knowledge domain questionnaire were given to the participants. then the attitude domain questionnaire was given to the participants, and the filled out questionnaires were collected. finally, a moulage was used to assess their hemorrhage control skills. after simulating the various vascular injuries on the moulage, emergency personnel were asked to perform remedial measures based on the checklist questions. then the scores for each section were recorded in the checklist by the researcher. 2.4. knowledge assessment tool in order to assess the knowledge level of participants, a questionnaire containing two scenarios in the form of key feature problem (kfp) was used. scenario 1 consisted of four questions regarding arterial bleeding control and scenario 2 included three questions regarding the management of amputated injuries. knowledge of ems staff in this domain was evaluated and given a score from 0 to 4. the knowledge score of the participants was categorized as low (mean score < 2), moderate (mean score: 2–3), and high (mean score: 3–4). 2.5. attitude assessment tool a questionnaire consisting of 14 items was used to survey the participants’ attitude toward bleeding and shock control measures. attitudes questionnaire was set based on a 5-point likert scale from "totally agree" to "totally disagree". scores of the participants’ attitude were categorized as follows: negative attitude (mean score: 3.5-5), moderate attitude (mean score: 2.5-3.5), and positive attitude (mean score: 1-2.5). 2.6. practice assessment tool after simulating various vascular injuries on the moulage, the included ems staff members were asked to perform remedial measures based on the checklist questions and the scores for each section were recorded in a checklist. the checklist was used to evaluate the hemorrhage control practice including capillary, venous, and arterial hemorrhage, as well as amputation management. skill of staff in doing each item was calculated as correct receiving 2 points, incomplete or incorrect this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e11 table 1: baseline characteristics of the studied emergency medical services (ems) staff variable number (%) age (year) <25 7 (4.2) 25-35 77 (46.7) 36-45 81 (49.1) educational field medical emergency 145 (87.9) nursing 17 (10.3) nurse anesthetist 3 (1.8) education level associate degree 130 (78.8) bachelor 35 (21.2) employment status contractual 90 (54.5) fee for service 47 (28.5) fixed term 17 (10.3) permanent 11 (6.7) marital status single 32 (19.4) married 133 (80.6) experience of working in dispatch (year) no experience 134 (81.2) <5 29 (17.6) 5-10 2 (1.2) experience of working in ems (year) <5 58 (35.2) 5-10 22 (13.3) 11-15 81 (49.1) 16-20 4 (2.4) experience of working in hospital (year) no experience 130 (78.8) <5 35 (21.2) receiving 1 point, and no practice receiving 0 point. average point of 1.7 to 2 was considered as good practice level, 1.2 to 1.7 as moderate, and lower than 1.2 as poor. 2.7. statistical analysis collected data were analyzed using spss software version 21. mean ± standard deviation or frequency (%) was used for reporting the findings. for investigating the relationship between knowledge, attitude, and practice with demographic characteristics of participants, analysis of variance (anova) was used. p<0.05 was considered as significant. 3. results 3.1. baseline characteristics of studied ems personnel 165 ems staff members with the mean age of 34.68 ± 5.11 years were evaluated (100% males). the demographic characteristics of the participants are presented in table 1. 49.1% of the participants were in the 36–45 years age group, 133 table 2: mean knowledge scores of the studied emergency medical services (ems) staff members regarding bleeding control data are presented as mean ± standard deviation items score examining injured person’s situation 2.28 ± 0.83 diagnosing the severity of hemodynamic status 2.90 ± 0.92 immediate measures to protect the injured person 2.58 ± 0.76 therapeutic measures during the transfer of the injured person 2.29 ± 0.62 actions in incomplete amputation of the limb 2.90 ± 0.67 actions in complete amputation of the limb 3.22 ± 0.68 actions in tightening tourniquet 2.43 ± 0.82 total 2.67 ± 0.39 table 3: mean attitude scores of the studied emergency medical services (ems) staff members regarding bleeding control data are presented as mean ± standard deviation attitude score fear 2.09 ± 0.56 importance of bleeding control 2.4 ± 0.58 confidence in bleeding control 1.76 ± 0.55 total 2.08 ± 0.43 (80.6%) were married, and 145 (87.9%) had an associate degree in pre-hospital emergency care. the majority of participants were contractually employed, 90(54.5%) had 11-15 years of working experience in ems, and 81 (49.1%) had no experience in emergency dispatch. 3.2. knowledge of participants the overall knowledge of participants regarding bleeding control of trauma patients was in the moderate range (2.67 ± 0.39). the knowledge of ems staff regarding the actions during complete amputation, status of injured patients, and medical measures during the transfer of injured patients were in high (3.22 ± 0.68), moderate (2.28 ± 0.83), and moderate (2.29 ± 0.62) range, respectively (table 2). there was a significant association between the knowledge levels of ems staff and age (p = 0.001), marital status (p = 0.039), educational level (p = 0.001), type of employment (p = 0.001), work experience as a dispatcher (p = 0.028), work experience in ems (p = 0.001), and work experience in hospital (p = 0.004). 3.3. attitude of participants the average attitude score of the participants regarding the fear of bleeding, the importance of bleeding control, and confidence in bleeding control were 2.09±0.56, 2.4±0.58, and 1.76±0.55, respectively (table 3). the anova results demonstrated that there was a significant association between of attitude of ems staff and type of employment (p = 0.07). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem y. sharifi et al. 4 table 4: practice scores of the studied emergency medical services (ems) staff members regarding bleeding control items categories* mean 2 1 0 investigation of extent of capillary hemorrhage 92.7 7.3 0.0 1.93 attention to creation of clotting in bleeding site 72.2 27.3 0.0 1.73 no manipulation of bleeding site 33.9 64.2 1.8 1.32 covering all damaged surface 81.2 17.0 1.8 1.91 venous bleeding control washing or cleaning the area to identify the bleeding site 81.8 18.2 0.0 1.81 applying direct pressure on site 68.5 31.5 0.0 1.68 applying pressure on site for 3 min 0 74.5 25.5 0.74 using pressure patching in case of bleeding continuation 44.2 52.7 3.0 1.41 not removing the original gauze layer on the site 16.4 75.8 7.9 1.08 attention to lower limbs for bleeding continuation 72.1 27.9 00. 1.72 arterial bleeding control identifying the exact location of the released artery 71.5 28.5 0.0 1.71 applying direct pressure on the site 73.9 26.1 0.0 1.74 squeezing the arterial pressure points in the arm or thigh 3.6 44.8 51.5 0.52 putting on a tourniquet two fingers above wound 40.6 59.4 0.0 1.4 not applying the tourniquet on the joint 70.3 29.7 0.0 1.7 visibility of the wound while tightening the tourniquet 86.7 11.5 1.8 1.84 loosening the tourniquet after bleeding stops 1.8 40.6 57.6 0.44 applying pressure on the mild bleeding site and then wound dressing 49.1 49.7 1.2 1.48 recording the time of putting on a tourniquet 94.5 5.5 0.0 1.94 visibility of damaged limb 92.7 6.7 0.6 1.92 bleeding control in amputated limb covering the site with sterile gas 44.8 55.2 0.0 1.44 wrapping crepe bandage twice over the site 10.3 73.3 16.4 0.94 continuing bandage around the wound 93.3 6.7 0.0 1.93 visibility of amputated limb 93.3 6.7 0.0 1.93 data are presented as percentage in each category. *2: correct; 1: incomplete or incorrect; and 0: no practice or failed. 3.4. practice of participants the total hemorrhage control proficiency score of the participants was 1.54 ± 0.25. the findings indicated that the mean practice score was 1.72 ± 0.46 in capillary hemorrhage control, 1.41 ± 0.25 in venous bleeding control, 1.47 ± 0.25 in arterial bleeding control, and 1.56±0.27 in bleeding control of the amputee limb (table 4). there was a significant association between the practice levels of ems staff and age (p = 0.001), marital status (p = 0.001), educational level (p = 0.001), type of employment (p = 0.001), work experience in ems (p = 0.001), and work experience in hospital (p = 0.001). 4. discussion the results of the present study showed that the knowledge, attitude, and practice of the studied ems staff regarding bleeding control were moderate, positive and appropriate, and incomplete, respectively. findings by ghaffari et al. suggested that the most important educational need of pre-hospital centers is cardiopulmonary resuscitation educational course, and a training course on examining consciousness level of the injured. in addition, three training courses were introduced as high priority courses for hospital emergency care centers, which included courses on how to deal with specific cases (such as amputation and bleeding control), advanced burn training courses, and advanced trauma life support, all of which had the same degree of importance, followed by self-care educational course in road accidents. the study indicated the necessity for formulating and holding educational programs on the extracted priorities to promote the skills of staff in prehospital and hospital centers (12). in the first scenario of this study, findings indicate that participants had moderate performance in examining injured person’s condition, diagnosis of severity of hemodynamic status, taking immediate measures to protect the injured person, and therapeutic measures during the transfer of the injured person. in addition, regarding the second scenario, their decisions for preserving the incomplete amputated limb and tightening the tourniquet was categorized as average; however, they had better decision-making regarding acting for complete amputation and were ranked as good. the studied ems personnel had a positive attitude toward fear of bleedthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e11 ing and shock as well as hemorrhage control, but given the importance of hemorrhage control and its irreparable consequences, more attention should be paid to these skills and ems personnel need more training in this regard. in their study, parvaresh et al. compared the effects of scenariobased and lecture-based education methods on knowledge and attitude of emergency medical technicians towards patients with chest trauma and the results showed that in the scenario-based education method, the mean knowledge and attitude scores were significantly higher (p <0.001). given the impact of scenario-based education and its role in making use of the learner’s intellectual abilities and their creativity, scenario-based education seems to be an appropriate alternative to traditional teaching methods (13). regarding hemorrhage control practice, findings indicated that in capillary bleeding control, the highest score belonged to examining the extent of capillary bleeding and the majority of staff paid attention to it. in addition, they often covered the entire surface of injured site correctly. however, paying attention to the clotting at the wound site, and not manipulating the site of bleeding was less considered. the average performance of the emergency personnel was satisfactory. regarding venous bleeding control, the findings showed that the majority of staff cleaned or rinsed the area correctly to identify the bleeding area and paid close attention to the lower limbs for the purpose of examining the continuation of bleeding. however, they were less skilled in using pressure patching in case of bleeding and not eliminating the original gauze layer on the site. in addition, despite having sufficient skill in applying pressure on the site, the majority of the staff showed negligence to maintaining pressure on the site for 3 minutes, their average performance was not generally satisfactory. regarding arterial bleeding control, the findings showed that the majority of staff paid close attention to the exact location of the released artery and the use of direct pressure on the site. but they did not show mastery on the use of pressure points for the arm and thighs. in terms of using the tourniquet, they didn’t pay attention to tightening the tourniquet and observing the joint. the majority knew that they should expose the injured limb and use the symbol of the tourniquet. however, their performance was poor regarding the last stage of using tourniquet, i.e. loosening the tourniquet, for creating mild bleeding current in order to preserve distal limb. their average performance was not generally satisfactory. regarding bleeding control in amputated limp, it was found that less attention was paid to sterility of dressing on the wound site. in addition, they did not show mastery on bandaging the amputated limb. however, they observed exposure of the amputated limb. their average performance was not generally satisfactory. in the study by oyeniyi et al. in two periods of 2005-2006 and 2012-2103 in huston trauma hospital, role of implementing a multi-purpose package of bleeding control was analyzed. results indicated that mortality did not correlate with gender and race, and the main factors resulting in death were brain damage and bleeding. by implementing this training package, mortality due to bleeding dropped from 36% to 25% (14). the results of the down port study on pre-hospital controlling of bleeding in traumatic patients indicated that the most common cause of traumatic deaths is bleeding, which usually occurs within three hours of injury. this study indicates that identification of severe bleedings should be performed as part of the primary evaluation on the scene, and potential clinical interventions should be performed as soon as possible. effective treatment of bleeding in the pre-hospital phase depends on quick identification of severe bleeding, direct anatomic control of vascular damage, bleeding restoration, and transfer to hospital (15). there is a need for formulating in-service educational courses to eliminate any deficiencies in bleeding control and improve the knowledge of pre-hospital emergency personnel for enhancing decision-making. 5. limitation special job condition and personal problems might have affected the psychological condition of the participants at the time of completing the questionnaire and this might have affected the answers given; however, this was out of the researchers’ control. additionally, observing the staff when implementing bleeding control skills might have influenced their performance. 6. conclusion the knowledge, attitude, and practice of the studied ems personnel regarding bleeding control were moderate, positive and appropriate, and incomplete, respectively. since bleeding is a life threatening condition and ems staff skills are critical in this issue, it seems that we need continuous education in this regard. 7. declarations 7.1. acknowledgements we would like to thank the pre-hospital emergency staff working in pre-hospital emergency stations of hormozgan province. we also appreciate the “student research committee” and “research & technology chancellor” in shahid beheshti university of medical sciences for their financial support of this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem y. sharifi et al. 6 7.2. author contribution all the authors met the 4 criteria recommended by the international committee of medical journal editors for gaining authorship. authors orcids yaser sharifi: 0000-0002-9903-3982 malahat nikravan mofard: 0000-0002-3003-8363 maryam jamsahar: 0000-0002-0216-6747 malihe nasiri: 0000-0003-1496-7442 mehdi safari: 0000-0002-0449-3688 7.3. funding/support none. 7.4. conflict of interest none. references 1. dadashzadeh a, dehghannejhad j, shams vahdati s, soheili a, sadeghi bazarghani h. the nature of prehospital medical interventions delivered to traumatic patients in tabriz. journal of urmia nursing and midwifery faculty. 2017;15(3):159-67. 2. drucker na, wang sk, newton c, editors. pediatric trauma-related coagulopathy: balanced resuscitation, goal-directed therapy and viscoelastic assays. seminars in pediatric surgery; 2019: elsevier. 3. rijnhout tw, wever ke, marinus h, hoogerwerf n, geeraedts jr lm, tan ec. is prehospital blood transfusion effective and safe in haemorrhagic trauma patients? a systematic review and meta-analysis. injury. 2019. 4. lima gl, byk j. trauma and early blood transfusion: the challenging hemorrhage management in jehovah’s witnesses. revista do colãl’gio brasileiro de cirurgiãţes. 2018;45(6). 5. matsushima k, conti b, chauhan r, inaba k, dutton rp. novel methods for hemorrhage control: resuscitative endovascular balloon occlusion of the aorta and emergency preservation and resuscitation. anesthesiology clinics. 2019;37(1):171-82. 6. ezati p, vaziri m, adli f. educational needs assessment in the medical emergency technicians of tehran emergency center. safety promotion and injury prevention. 2017;5(2):109-19. 7. hormozgan disaster and emergency medical management center [persian]. 2017. 8. berry mj, darby jr, o’byrne dm, dyson rm, sixtus r, holman sl, et al. arginine vasopressin improves cerebral perfusion following controlled haemorrhage in adult ewes. the journal of physiology. 2019. 9. hegvik jr, spilman sk, olson sd, gilchrist ca, sidwell ra. effective hospital-wide education in hemorrhage control. journal of the american college of surgeons. 2017;224(5):796-9. e1. 10. tobey n, waseem m. ems, chest injury. statpearls [internet]: statpearls publishing; 2019. 11. bayrami r, ebrahimipour h, hasanzadeh a. challenges in pre hospital emergency medical service in mashhad: a qualitative study. 2017. 12. ghaffari m, soori h, harooni j. prioritizing pre-hospital and hospital emergency staff’s training needs regarding traffic accidents: comparing the viewpoints of experts and target group. journal of health in the field. 2018;5(4). 13. parvaresh masoud m, farhadloo r, vahedian m, kashaninejad m, hasanpoor l, mohebi s. a comparison between the effects of scenario and lecture-based education methods on knowledge and attitude of emergency medical technicians towards patients with chest trauma. qom university of medical sciences journal. 2016;10(5):47-54. 14. oyeniyi bt, fox ee, scerbo m, tomasek js, wade ce, holcomb jb. trends in 1029 trauma deaths at a level 1 trauma center: impact of a bleeding control bundle of care. injury. 2017;48(1):5-12. 15. davenport r. haemorrhage control of the pre-hospital trauma patient. scandinavian journal of trauma, resuscitation and emergency medicine. 2014;22(1):a4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e11 appendix 1: knowledge measuring questionnaire to manage the bleeding and hemorrhagic shock (please select only four options from the following answers). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references daily situation report on coronavirus disease (covid-19) in iran march 14, 2020 national committee on covid-19 epidemiology ministry of health and medical education, ir iran total lab-confirmed cases 12,729 total associated deaths 611 total recovered cases 4,339 new cases 1,365 sex  male: 60%  female: 40% clinical management of confirmed cases  under ventilation: 8.4%  icu admission: 13%  isolation in the hospital: 45% duration of hospitalization to death  mean: 4.5 days  median: 4 days  minimum: 0 days  maximum: 21 days * the chance of death in patients under tracheal intubation was significantly higher than those who did not receive this supportive intervention. adjustment for the confounding effect of underlying diseases, as well as for the severity of covid-19 infection reduced the severity of the association by approximately 20%. however, the strength of association between death and intubation remains high and statistically significant. source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1,000 1,500 1 9 -f e b 2 0 -f e b 2 1 -f e b 2 2 -f e b 2 3 -f e b 2 4 -f e b 2 5 -f e b 2 6 -f e b 2 7 -f e b 2 8 -f e b 2 9 -f e b 1 -m a r 2 -m a r 3 -m a r 4 -m a r 5 -m a r 6 -m a r 7 -m a r 8 -m a r 9 -m a r 1 0 -m a r 1 1 -m a r 1 2 -m a r 1 3 -m a r 1 4 -m a r n u m b e r confirmed cases and associated deaths confirmed cases associated deaths 0 2 4 6 8 10 12 14 16 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 20 21 f re q u e n cy ( % ) number of days in hospital time between hospitalization to hospital death 0 2 4 6 8 10 12 14 16 18 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 f re q u e n cy ( % ) number of days in hospital time between hospitalization to hospital death (intubated vs. non-intubated patients)* non-intubated intubated archives of academic emergency medicine. 2019; 7 (1): e31 or i g i n a l re s e a rc h helicopter emergency medical services in 2017 kermanshah earthquake; a qualitative study ali sahebi1, zohreh ghomian1∗, mohammad sarvar2 1. department of health in disasters and emergencies, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 2. department of helicopter emergency medical services, ministry of health and medical education, tehran, iran. received: april 2019; accepted: may 2019; published online: 10 june 2019 abstract: introduction: becoming aware of experiences, and lessons learned in challenges can help optimize planning and improve efficiency and effectiveness. the present study aimed to address the challenges of helicopter emergency medical services (hems) from the viewpoint of the managers involved in hems in kermanshah earthquake. methods: this qualitative research was done using the content analysis method. the data were collected by semi-structured interviews. the study population consisted of directors who participated in management and transfer of injured people in the earthquake-stricken area of kermanshah. sampling was purposeful in the first stage and then by the snowballed method. results: in the present study, 479 codes were initially extracted regarding participants’ perspectives and experiences and after eliminating duplicates, 53 codes were finalized. after analyzing the data, 4 categories and 12 sub-categories were extracted. in this research, lack of integrated management and process-based preparedness were the subjects with the highest number of codes. conclusion: according to the findings of this study, it is suggested that comprehensive training programs should be implemented for effective management of the air emergency process during disasters such as earthquakes. keywords: emergency medical services; emergency medical technicians; transportation facilities; air ambulances; disaster planning; earthquakes cite this article as: sahebi a, ghomian z, sarvar m. helicopter emergency medical services in 2017 kermanshah earthquake; a qualitative study. arch acad emerg med. 2019; 7(1): e31. 1. introduction as a natural hazard, earthquake occurs 16 times a year on average all over the world, which causes a lot of human casualties and economic losses (1). according to the natural disasters recorded in 2014, in eastern mediterranean and north africa (mena) countries, 16 natural disasters were registered, 3 (19%) of which occurred in iran. the occurrence of these disasters in iran led to 38 deaths, 452,580 injured and homeless people, and 92,000 us $ economic damages (2). on saturday, november 12, 2017, at 21: 48 local time, an earthquake with a magnitude of 7.3 on the richter scale and 11kilometers depth occurred in ezgeleh district, kermanshah province. the destruction of 8 cities and 1930 villages, as well as 625 deaths and 15000 injured individuals, resulted from ∗corresponding author: zohreh ghomian; department of health in disasters and emergencies, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. tel: 09122766641, email: zghomian@sbmu.ac.ir this earthquake. more than 1,000 aftershocks were recorded during the days after the earthquake, the largest of which had a magnitude of 4.7 and occurred on november 13th, 2017 (1, 3, 4). in earthquake relief, victims, especially the critically injured, are transported by air emergency due to its high transport efficiency, and low mortality and disability rates. since ground emergency medical services (gems) are timeconsuming, helicopter emergency medical service (hems) plays a critical role in providing timely emergency medical services (ems) for patients in distant areas by reducing the time of transporting patients with critical situations to hospitals (5-8). hems plays an important role in the affected areas through triage, providing medical care, treating injured and transferring them to hospitals, as well as in transportation of equipment, personnel, accident victims and meteorological monitoring (9, 10). although hems is more expensive than gems, its use is increasing due to its multiple advantages. in fact, hems is an essential component of planning a comprehensive and local response to natural and manmade disasters for evacuating the injured people as soon as this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sahebi et al. 2 possible (11, 12). a comparison of the advantages of gems and hems showed that hems is preferred in special circumstances as it can warrant transportation of the injured to faraway hospitals in the least possible time. hems also benefits from experienced technicians who can effectively manage the disaster scene and triage of the injured (13, 14). considering the destruction of infrastructure, the importance of timely and effective responses, and the role of air emergency in the rapid transfer of injured to medical centers, the present study aimed to address the challenges of helicopter emergency medical services from the viewpoints of the managers involved in the hems in kermanshah earthquake. 2. methods 2.1. study design and setting a qualitative study was done with the content analysis approach (caa) using the graneheim and lundman (2004) method, from december 2017 to may 2018. using caa, codes, sub-categories, and categories were extracted the by an inductive process (15). in order to conduct the interviews, high-ranked directors of kermanshah earthquake management team from tehran, as well as operational managers from kermanshah and ilam provinces who participated in air emergency during kermanshah earthquake were included. 2.2. participants in the present study, experts and experienced individuals in relief and air transportation handling of the injured people were interviewed in two navigation and medical groups. the key persons involved in national planning for air emergency in kermanshah earthquake, members of the medical team and air emergency in iran, experienced hems providers to those injured in kermanshah earthquake, as well as personnel affiliated to the ministry of health and medical education, the red crescent society, and finally those who were willing to participate in the study, were included. members of military organizations were excluded from the study due to the impossibility of interviewing. the first interview was conducted with the head air emergency manager who served in an air emergency during kermanshah earthquake. after identifying the initial concepts, other participants were identified and selected. finally, 6 participants were included in two groups until data saturation was reached. 2.3. data collection sampling was purposeful in the first step and then the snowball method was applied. data collection was conducted through semi-structured and in-depth interviews with open and general questions (challenges hems faced during the western province earthquake). at the beginning of the interview the purpose of the study was explained to the participants. then, the main research question was asked. data collection was conducted until reaching data saturation and no new issues were introduced. all the interviews were conducted by phone and in person. the interviews lasted between 30 and 55 minutes (an average of 42 minutes). to resolve ambiguity and increase the clarity of the subject, questions were posed based on the participants’ impressions. when the participants felt tired and busy, the interviews were interrupted according to their will, and the next appointments were scheduled. with the permission of all participants, all the interviews were recorded using two digital devices and were then transcribed immediately. the interviews were conducted from december 2017 to may 2018. 2.4. data analysis data analysis was conducted using graneheim and lundman’s five-step content analysis method (15, 16). these steps included: first, the entire interview was transcribed. the manuscripts of the interviews were accurately read several times to reach an overview of the content. the manuscripts of the interviews were divided into units of meaning. then, the manuscript was summarized and initial codes were determined. all the codes were classified in terms of conceptual similarities and differences. finally, categories and subcategories were formed. after coding the first interview, a set of codes, categories, and sub-categories were extracted. data were reported based on a scientific approach to qualitative research. 2.5. trustworthiness the participants were chosen from the navigation and medical teams that were involved in hems to increase the credibility of the data. furthermore, the main challenges of this area were addressed. also, the participants had a rich experience in air emergency, in particular, during kermanshah earthquake. after analyzing each interview, the participants were revisited to verify the data provided by them (member check) if needed, corrections were considered. parts of the interview manuscript along with their codes and categories were sent to a number of experts in the field of qualitative studies to ensure the accuracy of the data analysis (external check). parts of the interview manuscript along with related codes and categories were also sent to three experts to review the analysis and express their corrective comments. an agreement rate of 85% was observed between the results (peer check). 2.6. ethical consideration verbal informed consent was received from all participants to observe ethical considerations. then, detailed descriptions were given on the purpose of the research, the interview method, the confidentiality of the information and the parthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e31 ticipants’ rights to either enter or refuse to participate in the study. also, no names were recorded in the interviews. the information confidentiality principle was strictly adhered to in each step of the research. 3. results 3.1. quantitative findings in the present study, six managers and pilots of the ministry of health and medical education and relief and rescue organization who were directly involved in air emergency following kermanshah earthquake were selected for interview. all participants were male with the age range of 30-50 and the average age of 40 years old. 40% of them had a medical doctor degree and 60% had a bachelor’s degree. the information obtained from the participants was based on their management experiences in air emergency in the 2017 kermanshah earthquake. 3.2. qualitative findings in the present study, 479 codes were initially extracted. considering participants’ perspectives and experiences and after eliminating duplicates, 53 codes were finalized. after analyzing the data, 4 categories and 12 sub-categories were extracted (tables 1-4). in this research, the topic with most codes was the lack of integrated management and processoriented preparedness. the sub-categories of this topic were interrupted comprehensive communication process, nonsystematic registration of statistics and information, lack of identification and tracking of referred injured patients, lack of systematic and parallel interagency coordination, and low prioritization of preparedness plans. according to participants’ views, the most important factor influencing air emergency was the lack of integrated management and process-oriented preparation, which had the highest number of codes. qualitative method of content analysis resulted in 4 main categories and 12 sub-categories as follows: lack of comprehensive training program this was one of the main categories extracted from the interviews. the inefficiency of the triage process, little attention to teaching safety laws and instructions, and ineffective training were the main sub-categories in this category. the most important sub-category was inefficiency of the triage process. in the interviews, it was repeatedly stated that pre-hospital and in-crisis triages were not well delivered, negating the prioritization of injured for being transported by air emergency. in air emergency, the transportation priority is for critical patients who should be transferred to treatment centers for advanced care as soon as possible. it was stated in the interviews that: “in kermanshah earthquake, every helicopter landed from every side like a bird. it was not clear whether or not the injured patient they had taken were candidates for aerial emergency or whether they had been under triage or not. the local hospitals in the earthquake area transferred the injured to the helicopter without triage and without any patient identifications” (participant number 3, a 37-year old man, air emergency). limitations in infrastructure development and a comprehensive program-based process this category comprised of contingency development for air emergency, lack of sustainable financial resources, and shortage in navigation and medical equipment. the most important sub-category of this category was the lack of navigation and medical equipment. regarding the navigation system, it was stated that these are not advanced equipment. there was no possibility of flying at night for the helicopters, and the mountainous condition of the area had further disturbed the flights. the helicopters did not have an air emergency design, but they had a multifunctional application. regarding the medical equipment in the helicopters, it was stated that these were unstandardized and unspecialized for air emergency. in fact, these were used in a ground emergency, which was inappropriately implemented on helicopters. it was stated in the interviews that “our medical equipment is sound based, which is not fit for being used in helicopters, instead they should have been visual based” (participant number 5, a 45-year old man, operational control center) and “the number of aerial ambulances is limited and they cannot all be called at the same time as their missions would remain on the ground” (participant number 1, a 52-year old man, air relief ). lack of integrated management and process-oriented preparedness this category included sub-categories of disruption in the comprehensive communication process, lack of a preparation program, unsystematic registration of statistics and information, not detecting and tracing referred injured patients, and lack of systematic and parallel coordination between organization. the most important sub-category in this category was the lack of systematic coordination between organization, which was assigned with the highest number of codes. it was noted that there was a lack of coordination between the air and ground emergency teams in the earthquake-stricken area. there was also a lack of coordination between the helicopters of the medical, military and the red crescent organizations and each received commands from their own organizations. overall, there was no unified command. it was reiterated in the interviews that “there was no emergenyc operating center (eoc) or air traffic control and guidance center on the disaster scene” (participant number 1, a 52year old man, air emergency). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sahebi et al. 4 lack of attention to the supply and maintenance of specialized human resources the sub-categories of this category included the lack of a systematic program for access to skilled and specialized workforce and the lack of reinforcement of internal motivational factors. it was expressed that the air medical team did not have sufficient knowledge and skills regarding air emergency. in addition, trained personnel had been frequently relocated. also, there was a shortage of skilled pilots to fly in bad weather conditions. there were implications in the interviews as “due to the fact that there has not been such a crisis in these areas over the past few years, the personnel of these centers did not know how to admit and transfer the injured to the helicopters” (participant number 4, a 48-year old man, hospital triage) and “but the nurse, flight engineers and pilots were not familiar with patient transfer protocols, they have not been sufficiently involved in the educational courses on how to communicate with medical teams and how to lay patients in helicopter. there is little common understanding between navigation and medical teams on flights and patients” (participant number 1, a 52-year old man, air emergency). 4. discussion the present study was a qualitative research on hems during kermanshah earthquake. according to the findings of the study, the main challenges in hems in this earthquake included the lack of comprehensive training program, limitations in infrastructure development and a comprehensive program-based process, lack of integrated management and process-oriented preparedness, and lack of attention to the supply and maintenance of specialized human resources. the results of other studies also indicated that lack of infrastructure and personnel, people and patients’ safety concerns, inadequate resource management, and concerns over the professional competence of personnel have been among the most important challenges faced by hems in iran (17). these challenges imply the necessity of reviewing hems in iran. monitoring compliance of practice with national standards and laws can play an effective role in improving the quality of hems. air emergency staff experience high levels of stress due to the closed space of helicopter, noises, vibrations and electronic communications, which necessitate appropriate training (18). based on the results of this study, one of the main challenges in providing hems in kermanshah earthquake was the lack of comprehensive training proram including inefficient triage process, lack of attention to safety rules and guidelines, as well as ineffective training. most of the participants pointed to the ineffectiveness of the triage process at the site of the incident. the goal of triage in natural disasters and mass casualty incidents (mci) is to prioritize the need to receive healthcare in stressful, difficult and complex situations. it has been argued that injured patients with less damage may receive faster healthcare in this condition. in such situations, if the health personnel have inadequate knowledge and skills, the triage process may not be performed in accordance with the standard protocols. furthermore, the intervention of the people and other staff involved in the relief can lead to impetuosity in triage and neglecting air transport indications. rapid and non-standard triage is done due to limited skill of the personnel. therefore, education can be used for enhancing the skills, as well as the knowledge of personnel (i.e. effective training) (19). the medical and navigational personnel as well as other paramedics should constitute a single working unit in the process of air transport during natural disasters, especially in those with mci. therefore, team training with a comprehensive approach including both common and specialized educational topics is needed. also, educational programs should be able to enhance medical and operational skills and knowledge. effectiveness of the education can also be evaluated through drills and exercise programs, which will lead to improvement of the process. another major challenge in air emergency during kermanshah earthquake was the lack of attention to the supply and maintenance of specialized workforce. the participants noted that in kermanshah earthquake air emergency team, there was a shortage of skilled and experienced staff and doctors in helicopters. air emergency is a specialized and effective relief service in disasters and requires expert and experienced personnel due to the different physiological responses of the human body on the ground and in the air. on the other hand, air transportation is carried out for highly injured patients who require complex and careful interventions and therefore, the provision of these services requires a high level of knowledge and skills. air emergency personnel play an effective role in managing medical responses to major accidents through rapid provision of advanced healthcare services (20). also, the presence of doctors in the helicopters can be useful because they can reduce the casualties by timely medical diagnosis, providing specialized services and treatments on the scene, and finally, injured patients can be properly transferred to specialized centers (21, 22). it was stated that insufficient attention was paid to teaching safety rules and regulations prior to kermanshah earthquake air emergency. lack of knowledge and not being aware of these rules and regulations can be hazardous for both medical and navigation teams. actually, air emergency teams usually pay less attention to the standard flight rules and regulations during the disasters with vastly destructed infrastructure and continuous increase in mortalities and injuries; and instead, focus on the transfer of injured patients to healthcare centers as this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e31 table 1: the first category and its sub-categories of helicopter emergency medical service (hems) challenges in kermanshah earthquake category sub-categories codes ineffective triage lack of training for the navigation team regarding triage of injured people following the earthquake the low skill of the medical team on how to conduct triage during an earthquake the low skill of hospital staff on how to conduct triage for mass casualty failure to implement air transfer protocols for those injured in earthquake the lack of paying little attention to safety lack of knowledge among the medical team about rules and protocols of flight and navigation comprehensiv rules and instructions inadequate knowledge of healthcare administrators regarding navigation rules training program low knowledge of hospital staff regarding the safety rules of air emergency ineffective training inadequate education of the medical team regarding navigation protocols inadequate education of the personnel deployed to the disaster area regarding air emergency inadequate skill training of the medical team to perform air emergency inadequate educational content regarding the navigation system for hospital staff lack of joint training of medical and navigation teams regarding the air-transport system lack of educational planning in recognizing the physiological impacts of aerial transportation lack of knowledge on the topography of the earthquake-stricken area among the navigation team table 2: the second category and its sub-categories of helicopter helicopter emergency medical service (hems) challenges in kermanshah earthquake category sub-categories codes contingency development for air relief insufficient helicopter pads in urban and intercity distances insufficient standard helicopter nests near the earthquakestricken area difficulties in providing temporary helicopter pads in the earthquake-stricken zone limitations in the long distance from the airport to the earthquake-stricken area infrastructure lack of sustainable financial resources delay in direct financial aids to air relief system before the start of operationdevelopment and impossibility of financial payments during operation (paypal)a comprehensive failure to estimate and predict the costs of air emergency in earthquake and crises program-based delay in the financial settlement of the companies involved in air emergency process high costs of air emergency services shortage in navigational and medical equipment insufficient standard navigation equipment insufficient advanced helicopter equipment inadequate helicopters for transferring the injured patients lack of basic medical equipment on the helicopter shortage of specialized medical equipment for a helicopter lack of standard medical equipment for air transportation improper design of helicopter space for applying as an aerial ambulance soon as possible. this situation can endanger both the patient and the rescue team. simultaneous training of navigation and medical teams improves the safety of rescuers and leads to positive outcomes in recovering patients. this can also augment effective management of difficult scenes and complications by the rescuer teams (23). another major challenge in this study was the lack of integrated management and process-oriented preparedness, which received the most codes. in fact, one of the subcategories repeatedly expressed by the participants was the lack of a systematic approach to patient care between organizations and parallel coordination. the process of air transthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sahebi et al. 6 table 3: third category and its sub-categories of helicopter helicopter emergency medical service (hems) challenges in kermanshah earthquake category sub-categories codes disruption in the comprehensive lack of a telecommunication system between the helicopter and the medical operations control center (eoc) communication process lack of a telecommunication system between helicopter and hospital emergency lack of a communication system between the helicopter and ambulance out of date navigation equipment unsystematic registration of statistics lack of a registration system for those injured in the earthquake and information: lack of identification and absence of a checklist for recording the severity of injuries in victims transferred by air emergency tracking of the referred injured patients lack of integrated lack of systematic and parallel lack of a contract between the air transportation system and the oil company to provide helicopter fuel management and coordination between domains inconsistency between the navigation and medical teams for optimal transfer of the injured process-based absence of an online database for the aviation team to obtain meteorological conditions of the flight and earthquake-stricken area from the meteorological center preparation inconsistency in the timely delivery of injured people from a helicopter to the land emergency inconsistencies between medical, military, and the red crescent teams in the aerial transportation of the injured lack of a joint organization managing others involved in the aerial transportation of the injured in the earthquake-stricken area lack of a comprehensive and coordinated responsive center between organizations involved in air assistance and aerial transportation low priority of readiness programs failure to schedule helicopters recruitments to the earthquakestricken area as soon as possible lack of planning to prepare a hazard map from the earthquakestricken area lack of air emergency preparedness programs in response to crisis/earthquake failure to conduct joint trainings between organizations involved in air emergency lack of contingency programs for air emergency process in earthquake table 4: fourth category and its sub-categories of helicopter emergency medical service (hems) challenges in kermanshah earthquake category sub-categories codes lack of attention to the lack of programs to identify lack of qualified, specialized, and skilled medical staff for delivering air emergency supply and maintenance specialized and skilled workforce the frequent relocation of trained personnel in relief units of specialized human lack of high-skilled pilots for flying in different weather conditions during natural disasters resources not encouraging internal lack of a registration system for those injured in the earthquake motivational factors low interest in air relief forces to serve in the earthquake-stricken area portation is a complex operation performed by the participation of various organizations. these organizations, however, have their own rules and guidelines. therefore, the implementation of specific rules and procedures of these organizations in response to disasters results in incoordination. according to the participants, in kermanshah earthquake, the medical operation control center did not monitor helicopters, and they transported the patients in coordination with their own operational control center (eoc). in air emergency, using online system and satellites, the incithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e31 dent zone is controlled by managers of various organizations involved in disasters. this coordinated process increases the knowledge and awareness of the managers regarding the situation (24). the command and control system is used to create coordination at the scene of the incident, and the dispatch is used to establish coordination among different relief units (25). the implementation of a unified and integrated command system in the site of an incident can enhance organizational coordination. the incident command system (ics) is an equally structured management tool for coordinating and controlling respondent teams in major accidents. the existence of structures such as the eoc and ics can be of help in response to disasters (26, 27). limitations in infrastructure and process development based on a comprehensive program have been among other challenges in air emergency during kermanshah earthquake. shortage in sustainable financial resources was one of the subcategories in this category. a lot of money is spent on the maintenance of helicopters, pilot training, and each air emergency mission. given the high costs of air emergency services, it is essential that their missions be equipped with appropriate triage, as well as standards and protocols for air transportation of patients. this will result in proper application and cost-effectiveness in this process. in other countries, the cost of each mission and every hour of the mission of the air emergency is high and reaches several thousand dollars. the difference in the costs of air emergency is due to the types of recruited helicopters, rescue staff, and the duration of the mission (28). 5. recommendations: the following recommendations are made for improving the quality of air emergency transportation services in emergencies and disasters: 1establishment of a central coordinating center for unified management of air emergency transportation between the military, ministry of healthcare, and red crescent organizations. 2integrated education and training courses for all team members involved in the process of patient delivery in air emergency transportation services during flight based on assessment of educational needs. 3using modern medical helicopters that have been equipped with advanced medical and flight navigation equipment. 6. limitations: in this study, access to and interview with military experts were not possible; however, if access would have been possible, researchers could benefit from the experience of military experts in helicopter emergency medical services. 7. conclusion according to the findings of this study, it is suggested that comprehensive training programs should be implemented for effective management of air emergency process during disasters such as earthquakes. 8. appendix 8.1. acknowledgements the authors would like to thank all the participants for their contribution to the study. we would also like to thank all colleagues, stakeholders, and staff members who kindly cooperated in conducting this study. 8.2. author contribution study design, advocacy, and supervision were done by zohreh ghomian and interviews, analysis and manuscript preparation were done by ali sahebi and mohammad sarvar. the final version of the manuscript was accepted by authors. authors orcids ali sahebi: 0000-0003-4662-8998 zohreh ghomian: 0000-0002-3644-7379 8.3. funding/support none declared. 8.4. conflict of interest the authors do not have any conflict of interests to declare. references 1. 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terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion recommendations: limitations: conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e22 ca s e re p o rt stress cardiomyopathy (takotsubo syndrome) following accidental methadone poisoning; report of two pediatric cases khatereh dehghani1∗, mohammad shojaie2, amir hossein pourdavood3, mohammad khajouei4 1. department of cardiology, jahrom university of medical sciences, jahrom, iran. 2. cardiology department, non-communicable research center, jahrom university of medical sciences, jahrom, iran. 3. department of surgery, kerman university of medical sciences, kerman, iran. 4. nanotechnology research institute, chemical engineering department, babol (noshirvani) university of technology, babol, iran. received: november 2018; accepted: december 2018; published online: 9 march 2019 abstract: methadone poisoning has become more common in the pediatric population due to extensive use of methadone maintenance therapy (mmt). it is associated with decreased level of consciousness, coma, respiratory distress and cardiac intoxication. the cardiac complications have been reported to be qt prolongation, torsade de pointes, coronary artery disease, arrhythmia, stress cardiomyopathy and death. we herein report two pediatric patients with accidental methadone poisoning who developed stress cardiomyopathy and cardiac failure. the first case was a 4-yaer-old girl and the second one was an 18-month-old girl both being accidentally poisoned with methadone syrup and were brought with decreased level of consciousness. both were diagnosed to suffer from congestive heart failure based on echocardiography. however, the first case passed away despite appropriate treatment, while the second one survived the condition and was discharged with good condition and was symptom free at 6-month follow-up. keywords: methadone; toxicity; cardiomyopathy; pediatrics; case reports cite this article as: dehghani kh, shojaie m, pourdavood a h, khajouei m. stress cardiomyopathy (takotsubo syndrome) following accidental methadone poisoning; report of two pediatric cases. arch acad emerg med. 2019; 7 (1): e22. 1. introduction methadone is a synthetic opioid which was first introduced in germany between 1937 and 1939. a long half-life of 25 to 52 hours and high analgesic effects, makes methadone suitable for maintenance therapy in opium addicts and is currently used as the basis of withdrawal management as methadone maintenance therapy (mmt) (1). methadone poisoning is among the catastrophic intoxications with a wide range of clinical presentations including decrease in the level of consciousness, coma, apnea, respiratory suppression, and death (2). in recent years, a significant rise in the use of different forms of methadone (tablet and syrup) in iran has led to increase in reported rates of accidental poisonings ∗corresponding author: khatere dehghani; cardiology department, jahrom university of medical sciences, jahrom, iran. po box: 74148-46199 tel/fax: +98-715-4340405 email: kh.dehghani@jums.ac.ir especially in pediatric populations (3, 4). methadone overdose in children has been associated with respiratory distress, cardiac toxicity and decreased level of consciousness. it has also been associated with nausea and vomiting, myosis, dyspnea and early seizures (5, 6). respiratory suppression has been reported to be the most lethal complication of methadone intoxication, which is initialized approximately 12 hours after drug ingestion (7). a common cardiac manifestation in methadone overdose is qt prolongation, which can lead to torsade de pointes and may result in death (8). other effects include changes in qt dispersion, pathological u waves, stress cardiomyopathy (takotsubo syndrome), brugada-like syndrome, and coronary artery diseases (9). we herein report, two cases of stress cardiomyopathy in pediatrics following methadone poisoning. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem kh. dehghani et al. 2 2. case presentation 2.1. case 1 a 4-year-old girl was brought to our emergency department with decreased level of consciousness since an hour before. she was the second child of the family whose father was an opium addict on mmt. the methadone had been kept in a bottle like pediatric syrup bottle and the girl was mistakenly given methadone instead of cough syrup by her mother. upon arrival she had a glasgow coma score (gcs) of 7/15, a heart rate of 145 bpm, a respiratory rate of 32 breaths/minute, blood pressure of 132/76 mmhg and a temperature of 36.8◦c with an oxygen saturation of 85% in room air. her pupils were myotic and responsive to light and other examinations were within normal limits, so treatment by naloxone (0.1 mg/kg) was started for her. since there was no response to the initial therapy, she was admitted to the intensive care unit (icu) and maintenance naloxone (0.16 mg/kg/h) was started. her electrocardiogram showed tachycardia with qt interval of 440 milliseconds and st segment elevation in avr and t wave inversion v1, v2 and v3 (figure 1). laboratory investigations revealed white blood cell (wbc) count of 31,800 /mm3, hemoglobin of 11.9 mg/dl, platelet count of 291,000/mm3, blood urea nitrogen (bun) of 24 mg/dl, creatinine (cr) of 1.7 mg/dl, sodium of 133 meq/l, potassium of 6 meq/l, blood sugar of 113 mg/dl, calcium of 8.9 mg/dl, creatine phosphokinase (cpk) of 32,000 iu/l, lactate dehydrogenase (ldh) of 6,030 iu/l, troponin of 6.18 u/l, prothrombin time (pt) of 24.4 sec, partial thromboplastin time (ptt) of 48 second, sgot of 123 u/l and sgpt of 1545 u/l. transthoracic echocardiography revealed left ventricular ejection fraction of 25% with akinesia of posterior wall and hypokinesia of septum. she was diagnosed with stress cardiomyopathy and acute heart failure and thus the management of heart failure including diuretics and inotropes was stared for her. on the second day of admission, she developed respiratory arrest and thus was intubated and connected to the ventilator with gcs of 3/15. brain ct-scan showed bilateral cerebellar infarction and edema and diffuse brain edema. neurologist was consulted and medical management of intracranial hypertension was started. the patient received hypertonic saline (5mg/kg as bolus dosage and 3mg/kg every 6 hours) and mannitol (1 mg/kg/dose). however, unfortunately she died on the third day despite intensive care management. 2.2. case 2 an 18-month-girl was transferred to our center from a primary healthcare center due to decreased level of consciousness several hours prior to presentation. she was reported to be treated with 3cc of methadone solution by mistake figure 1: the 12-lead electrocardogram (ecg) of the first patient demonstrating tachycardia with qt interval of 440 milliseconds and st segment elevation in avr and t wave inversion v1, v2 and v3. instead of diphenhydramine because of coryza signs and symptoms. on admission to the primary center, she had a gcs of 14/15, a heart rate of 135 bpm, a respiratory rate of 26 breaths/minute, blood pressure of 127/67 mmhg and a temperature of 36.8◦c with an oxygen saturation of 98% in room air. her pupils were myotic with response to the light. with the primary impression of methadone poisoning, naloxone (0.1 mg/kg) had been administered in the primary center and then she was transferred here. she was also reported to have had 2 episodes of tonic-clonic convulsions in the ambulance during the transfer for which diazepam (0.1 mg/kg) was administered. on admission to our center, she had gcs of 8/15 and she had bradypnea with abdominal respiration and o2 saturation of 84% without oxygen supplement, blood pressure of 117/67 mmhg, a temperature of 37.5◦c with myotic pupils that were reactive to light and upward plantar reflex (babinski), so naloxone infusion was continued (0.16 mg/kg/h). she was intubated and transferred to icu. she had two episodes of tonic clonic convulsion for which midazolam infusion was started (0.05 mg/kg/hr). laboratory examination revealed wbc count of 18,000/mm3 (88%pmn, 11%lymphocyte), hemoglobin of 8.6 mg/dl, platelet count of 390,000/mm3, bun of 18 mg/dl, cr of 0.7 mg/dl, sodium of 140 meq/ml, potassium of 4.7 meq/l, blood sugar of 102 mg/dl, cpk of 3,050 iu/l, ldh of 2,375 iu/l, pt of 20 second, ptt of 28 second, sgot of 6220 u/l, sgpt of 5740 u/l and crp of 73 mg/l. the ecg also showed sinus tachycardia and prolonged qt interval (figure 2). on the second day, she had another episode of convulsion with decrease in o2 saturation. she developed bilateral fine rales in lung examination in favor of pulmonary edema, so infusion of furosemide (1 mg/kg q2h) was started. chest radiography revealed pulmonary edema. brain ct scanning demonstrated a small this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e22 figure 2: the 12-lead electrocardogram (ecg) of the second patient demonstrating sinus tachycardia and prolonged qt-interval. area of ischemia and hydrocephaly. in echocardiography, ejection fraction of 15% with diffuse hypokinesia and mild mitral valves regurgitation has been showed. she was diagnosed to suffer from stress cardiomyopathy for which management of heart failure was started. after 3 days of conservative management with naloxone (0.1 mg/kg/dose) and phenobarbital (0.15 mg/kg q12h) the patient developed spontaneous respiration and was extubated 2 days later. her gcs increased to 14/15 and echocardiography revealed normal cardiac function. she was discharged from the hospital on the 12th day while she was completely awake with normal echocardiography. on the 6month follow-up she had normal daily activity and normal echocardiography without signs of cardiac failure. she did not have any seizure so the anticonvulsants were tapered. 3. discussion methadone is a powerful analgesic drug that affects mu receptors and it is majorly used for treatment of opioid addiction as well as for pain relief (9, 10). poisoning by methadone is very hazardous and may lead to death because of its irreversible complications; in most countries it is kept in containers that it is not easy for children to open and also warning labels attached on the containers (11). however, in iran there is not any special bottle for methadone in form of syrup and it is kept in bottles like pediatric syrup bottles, so the rate of pediatric methadone poisoning is relatively high and a large number of hospitalizations in emergency ward are due to this type of poisoning (12). unfortunately, this drug is sometimes administered to children instead of other pediatric syrups by mistake and because of its silent symptoms such as drowsiness and loss of consciousness, it’s not detected early on by parents and they usually find out several hours after drug ingestion, when it is too late to help these children survive (3, 9). complications of methadone toxicity are drowsiness, decreased level of consciousness, respiratory failure, myosis, hypotension, acute respiratory distress syndrome (ards), brain damage and other end organ damages (9). respiratory suppression is the main cause of death in patients with methadone overdose, it may lead to severe hypoxia that can result in lung and brain injury as well as renal and liver dysfunction (13). some other adverse effects include ataxia, hearing loss, cerebellitis and chest rigidity (14, 15). the cardiac complications of methadone toxicity are rare and include qt prolongation and subsequent torsade de pointes mainly because of the electrolyte imbalance (9). we herein reported two pediatric patients with methadone poisoning who developed severe left ventricular dysfunction and stress cardiomyopathy leading to death in one. stress cardiomyopathy (tako-tsubo syndrome) is defined as left ventricular dysfunction and ecg changes that mimic acute myocardial infarction without any evidence of involvement of coronary arteries (16, 17). it is more common in postmenopausal women and an acute medical illness or emotional/physical stress may typically trigger this syndrome. it has been demonstrated that huge release of catecholamines (maybe due to opioid withdrawal) may be responsible for development of this cardiomyopathy. two cases of takutsubo syndrome have been reported in relation with acute opioid withdrawal. lemesle et al. (16), reported the first case as a result of methadone withdrawal secondary to drugdrug interaction. however, we observed this phenomenon in 2 pediatric cases who were admitted to our center with methadone poisoning and the mortality rate was as high as 50% in our patients. all the previously reported cases were adults but our patients were children. two cases of takutsubo cardiomyopathy have been reported previously, but both of them had happened after methadone withdrawal not methadone poisoning (16, 17). in our patients, autopsy was not done in the first patient to clear the cause of her cardiac damage and the condition of the second one wasn’t suitable for cardiac mri to evaluate the cardiac structure and function. further evaluation on other cases is needed to clear the effect of methadone and its metabolites on the myocardium. 4. conclusion methadone overdose can cause cardiac injury leading to cardiac failure and death. toxic metabolites of methadone may cause myocarditis and cardiac failure while excessive catecholamine release could be another explanation for this phenomenon especially in young children. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem kh. dehghani et al. 4 5. appendix 5.1. acknowledgements the authors would like to thank their colleagues, for their support. we would also like to thank the patients and their family for their cooperation and allowing us to publish the material. we would like to acknowledge the editorial assistance of diba negar research institute for improving the style and language of the manuscript. 5.2. authors contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. authors’ orcids khatereh dehghani: 0000-0002-7980-3265 mohammad shojaei: 0000-0003-1312-5913 amir hossein pourdavood: 0000-0002-6211-5941 mohammad khajouei: 0000-0002-0576-761x 5.3. conflict of interest none of the authors have any conflict of interest to declare regarding the manuscript. 5.4. funding no fund was received for the manuscript and the manuscript is considered the authors’ own work. references 1. joseph h, stancliff s, langrod j. methadone maintenance treatment (mmt): a review of historical and clinical issues. mt sinai j med. 2000;67(5-6):347-64. 2. boyer ew, mccance-katz ef, marcus s. methadone and buprenorphine toxicity in children. am j addict. 2010;19(1):89-95. 3. sharif mr, nouri s. clinical signs and symptoms and laboratory findings of methadone poisoning in children. iran j pediatr. 2015;25(1):e176. 4. kashani p, safari s, hatamabadi h, dolatabadi aa, manouchehrifar m, tabrizi md. characteristics of methadone intoxicated children presenting to emergency department; a cross sectional study. emergency. 2017;5(1). 5. gheshlaghi f, izadi-mood n, mardani a, piri-ardekani mr. dose-dependent effects of methadone on qt interval in patients under methadone maintenance treatment. asia pacific journal of medical toxicology. 2013;2(1):6-9. 6. aghabiklooei a, shadnia s, hassanian-moghaddam h, zamani n. acute respiratory distress syndrome caused by methadone syrup. arh hig rada toksikol. 2013;64(3):439-43. 7. jabbehdari s, farnaghi f, shariatmadari sf, jafari n, mehregan ff, karimzadeh p. accidental children poisoning with methadone: an iranian pediatric sectional study. iran j child neurol. 2013;7(4):32-4. 8. mayet s, gossop m, lintzeris n, markides v, strang j. methadone maintenance, qtc and torsade de pointes: who needs an electrocardiogram and what is the prevalence of qtc prolongation? drug alcohol rev. 2011;30(4):388-96. 9. alinejad s, kazemi t, zamani n, hoffman rs, mehrpour o. a systematic review of the cardiotoxicity of methadone. excli journal. 2015;14:577. 10. chen a, ashburn ma. cardiac effects of opioid therapy. pain med. 2015;16 suppl 1:s27-31. 11. jepsen f, ryan m. poisoning in children. current paediatrics. 2005;15(7):563-8. 12. gibson jc, vulliamy a. accidental methadone poisoning in children: a call for canadian research action. child abuse negl. 2010;34(8):553-4. 13. aghabiklooei a, edalatparvar m, zamani n, mostafazadeh b. prognostic factors in acute methadone toxicity: a 5-year study. j toxicol. 2014;2014:341826. 14. van gaalen fa, compier ea, fogteloo aj. sudden hearing loss after a methadone overdose. eur arch otorhinolaryngol. 2009;266(5):773-4. 15. lynch re, hack ra. methadone-induced rigid-chest syndrome after substantial overdose. pediatrics. 2010;126(1):e232-4. 16. lemesle f, lemesle f, nicola w, pierre jonville-bera a. first case of stress cardiomyopathy as a result of methadone withdrawal secondary to drug-drug interaction. am j emerg med. 2010;28(3):387.e5-6. 17. spadotto v, zorzi a, elmaghawry m, meggiolaro m, pittoni gm. heart failure due to ’stress cardiomyopathy’: a severe manifestation of the opioid withdrawal syndrome. eur heart j acute cardiovasc care. 2013;2(1):84-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 120 emergency (2015); 3 (3): 120-121 casr report periumbilical pain with radiation to both legs following tarantula bite; a case report mahboob pouraghaei1, samad shams vahdati2*, ibrahim mashhadi1, taranoom mahmoudieh3 1. department of emergency medicine, tabriz university of medical science, tabriz, iran. 2. road traffic injury research center, emergency department, tabriz university of medical science, tabriz, iran. 3. medical faculty, tabriz university of medical science, tabriz, iran. *corresponding author: samad shams vahdati; department of emergency medicine, sina hospital, azadi avenue, tabriz, iran. tel: +989141156941; email: sshamsv@yahoo.com; shams@tbzmed.ac.ir received: march 2015; accepted: april 2015 abstract tarantulas have recently become as pets in most parts of the world that increased the probability of encountering emergency physicians with patients hurt with these spiders. their attacks usually do not cause general manifestation, however there are some case reports in this regard. here, a 40-year-old man was reported who was referred to the emergency department with severe periumbilical pain that radiated to both legs and diagnosed as a victim of tarantula bite. such symptoms usually are belonging to other spiders like black widow spider, but it seems that tarantula can mimic them in some cases, too. key words: spider bites; bites and stings; pets; spider venoms cite this article as: pouraghaei m, shams vahdati s, mashhadi i, mahmoudieh t. periumbilical pain with radiation to both legs following tarantula bite; a case report. emergency. 2015;3(3):120-1 introduction: tarantula is a large spider which usually be found in tropical and subtropical areas, but recently has become as pets in worldwide (1). consequently, it is more likely that emergency physicians encounter with patients that hurt with these spiders. they are nonaggressive arthropods that if to be forced to defend themselves, flick their needle-like abdominal hair at the target and may rarely bite (2). though tarantulas may look scary, most of their species are relatively harmless, just a few cases may be dangerous to humans (1). their attacks generally do not cause general manifestation, however there are some case reports in this regard (3, 4). here, an unusual presentation of tarantula bite was reported. case report: a 40-year-old man referred to the emergency department (ed) with severe colicky periumbilical pain, which was non-positional and radiated to both legs. pain was started from the last day and progressed until arriving to the ed. the patient did not have recent trauma history, except heavy lifting, and also any positive past medical history. on admission time, tachycardia of 110/minute revealed a sinus tachycardia on 12 lead electrocardiogram (ecg) and hypertension of 220/110 mmhg in the right arm and 190/100 mmhg in the left arm. on physical examination, the patient had erythematous and edematous face. the abdominal examination was soft and did not have tenderness or guarding. straight leg raising (slr) test did not aggravate the pain and all other systems were normal too. blood gas analysis and biochemical profile did not reveal any positive findings. with suspicion of large vessel insult abdominal sonography, chest radiography (cxr) and double contrast enhanced computed tomography (ct) were performed, all reported as normal. after ruling out above-mentioned critical impressions, with attention to the history of heavy lifting, herniated disk was suspected so that magnetic resonance imaging (mri) was requested in which no abnormalities were found. during all these examinations, despite palliative treatments, the patient had severe pain without improvement. unfortunately, the patient was discharged against medical advice and admitted again after 24 hours with right leg swelling and erythema. in this time, the patient was exposed and several bite-like sites were surprisingly found on his right leg. another comprehensive history taking revealed that patient was bitten by tarantula at his home. discussion: tarantulas usually flick their hair at the target, so the most clinical presentations of biting are local allergic reactions including irritation, pruritus, edema, and erythema. if the flicked hair takes place in eye, can result in redness and keratitis. their bite usually sense as mild pain similar to a pinprick, but can cause severe pain, muscle spasms, local swelling, and numbness or even this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 121 emergency (2014); 3 (3): 120-121 arthritis (3, 4). in spite of all above-mentioned, there is no properly documented case of permanent deficit or death following the tarantula bite (5). such severe symptoms almost always belong to other spiders like black widow spider (6). surprisingly, our case had some of these symptoms in spite of being bitten by tarantula. therefore, we would consider that tarantula bite can mimic symptoms of black widow spider envenomation. laboratory tests and imaging studies are not helpful for evaluation and management (7). in the case of tarantula bite, washing the site with soap and water and applying a cool compress or even an ice cube can reduce the local symptoms. treatment in the ed is usually conservative and involves administration of antihistamines, corticosteroids, and analgesics (8). although no specific treatment exists, it has been suggested that calcium supplements may be beneficial to relieve the muscle spasms (4). there is no report of recurrent or delayed reaction yet, so except for rare cases of anaphylaxis, all patients can be discharged after symptom resolution. acknowledgments: none conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. de haro l, jouglard j. the dangers of pet tarantulas: experience of the marseilles poison centre. clin toxicol. 1998;36(1-2):51-3. 2. watts p, mcpherson r, hawksworth nr. tarantula keratouveitis. cornea. 2000;19(3):393-4. 3. takaoka m, nakajima s, sakae h, et al. tarantulas bite: two case reports of finger bite from haplopelma lividum. jpn j tox. 2001;14(3):247-50. [japanese ]. 4. dinamithra n, sivansuthan s, johnson p, nishshanka j. clinical presentation and outcome of sri-lankan ornamental tarantula poecilotheria fasciata spider bite: a case report. anuradhapura med j. 2013;7(1):10-2. 5. demain jg. papular urticaria and things that bite in the night. curr allergy asthma rep. 2003;3(4):291-303. 6. clark rf, wethern-kestner s, vance mv, gerkin r. clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. ann emerg med. 1992;21(7):782-7. 7. diekema ds, reuter dg. arthropod bites and stings. clin pediatr emerg med. 2001;2(3):155-67. 8. rahmani f, khojasteh smb, bakhtavr he, rahmani f, nia ks, faridaalaee g. poisonous spiders: bites, symptoms, and treatment; an educational review. emergency. 2014;2(2):548. http://emedicine.medscape.com/article/135065-overview emergency. 2018; 6 (1): e11 or i g i n a l re s e a rc h emergency department bedside ultrasonography for diagnosis of acute cholecystitis; a diagnostic accuracy study babak shekarchi1, seyed zia hejripour rafsanjani2, nima shekar riz fomani2,3∗, mojtaba chahardoli3 1. department of radiology, school of medicine, aja university of medical sciences, tehran, iran. 2. emergency department, besat hospital, school of medicine, aja university of medical sciences, tehran, iran. 3. emergency department, firouzgar hospital, iran university of medical sciences, tehran, iran. received: december 2017; accepted: december 2017; published online: 20 january 2018 abstract: introduction: using bedside ultrasound in diagnosing acute cholecystitis in the emergency department (ed) can save time, help the decision making process and allocate resources wisely. this study aimed to evaluate the diagnostic accuracy of bedside right upper quadrant (ruq) ultrasonography in detection of acute cholecystitis. methods: in this diagnostic accuracy study, patients presenting to ed, suffering from ruq pain in favor of acute cholecystitis underwent ruq ultrasonography in emergency and radiology departments and interrater agreement between reports was calculated. results: 342 patients with the mean age of 53.92 ± 11.18 (20 – 83) years were studied (63.2% female). the number of patients with at least one sonographic finding of acute cholecystitis were 53 (15.50%) and 48 (14.00%) based on ed and radiology reports (kappa = 0.826). sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios of bedside sonography were 89.58 (95%ci: 76.55 – 96.10), 96.59 (95%ci: 93.63 – 98.29), 81.13 (95%ci: 67.58 – 90.11), 98.26 (95%ci: 95.77 – 99.36), 4.30 (95%ci: 2.42 – 7.62) and 0.017 (95%ci: 0.007 – 0.041), respectively. conclusion: there was a very good agreement between ed and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. sensitivity and specificity of bedside ruq sonography were 89.58 and 96.59, respectively. keywords: cholecystitis, acute; ultrasonography; diagnostic imaging; emergency service, hospital; emergency medicine © copyright (2018) shahid beheshti university of medical sciences cite this article as: shekarchi b, hejripour rafsanjani seyed z, shekar riz fomani n, chahardoli m. emergency department bedside ultrasonography for diagnosis of acute cholecystitis; a diagnostic accuracy study. emergency. 2018; 6(1): e11. 1. introduction a round 10 to 20 percent of the normal population in the us have biliary stone but only 1 to 2 percent of them get symptomatic (1, 2). the most important complication of gallbladder stones is acute cholecystitis. the main signs and symptoms of acute cholecystitis are right upper quadrant (ruq) pain, fever and murphy sign (3). these findings guide the physicians towards proper diagnosis but they are not enough and they do not have adequate diagnostic yield to be precise (4, 5). ultrasonography, hepatobiliary iminodiacetic with scintiography (hida) scan, and abdomi∗corresponding author: nima shekar riz fomani; emergency department, firoozgar hospital, valiasr square, tehran, iran. email: nima.shekarriz@gmail.com mobile phone: +989124984280 nal computed tomography scan are some of the available and helpful diagnostic tools with different accuracies in diagnosis of acute cholecystitis (6-8). ultrasound has been one of the most sensitive and specific modalities in acute cholecystitis diagnosis and has become the first line modality in many guidelines (8). it is vastly available, accurate and cost-beneficial and has been called “the 21st century visual stethoscopes” (9-12). the most important sonographic findings of acute cholecystitis are gallbladder stone, increased wall thickness, and wall edema as well as fluid around the gallbladder (13, 14). zenobi et al. showed the high positive predictive value of right upper quadrant (ruq) ultrasonography in emergency settings for diagnosis of acute cholecystitis (15). kendall et al. estimated the sensitivity 96% and specificity 88% of sonographic murphy sign for diagnosis of acute cholecystitis in an emergency setting (16). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. shekarchi et al. 2 there was a recent massive improvement in point of care ultrasound science and technology, which made it useful for daily practice; however, there is still the question of accuracy. therefore, the present study aimed to evaluate the diagnostic accuracy of bedside ruq ultrasonography by trained emergency medicine residents or attending emergency physicians in detection of acute cholecystitis. 2. methods 2.1. study design and setting in this diagnostic accuracy study, patients presenting to emergency department of firouzgar (a tertiary center for gastrointestinal diseases) and besat hospitals, tehran, iran, from 2015 to 2017, suffering from ruq pain in favor of acute cholecystitis underwent bedside ultrasonography. then, the accuracy of bedside ultrasonography performed by trained emergency residents or attending emergency physician was calculated, considering the radiology department reports as a standard. the study protocol was approved by ethics committee of aja university of medical sciences and researchers adhered to all aspects of ethical practice and confidentiality of patients’ information. informed consent was obtained before patients’ enrollment. 2.2. participants patients with ruq or epigastric pain suspected to acute cholecystitis who were brought to the mentioned emergency departments were enrolled using non-probability sampling techniques. patients with history of biliary disease, jaundice, and cholecystectomy as well as intubated, pregnant and cases < 18 years old were excluded. 2.3. investigation following physical examination and history taking, each case was examined via bedside ruq abdominal ultrasonography in the emergency department. all exams were either done by attending emergency physicians, expert in point of care ultrasound, or under their direct supervision by trained emergency residents. ultrasonographies were done by a 2-5 mhz curve transducer by an hm-70 samsung device or an mturbo sonosite device. the examinations were started from the subcostal area. in case of no view from subcostal or intercostal window, the patient was asked to sit upright or rotate to the left lateral decubitus position. after examination, the sonographer filled out an online form consisting of 5 yes-no questions regarding the presence or absence of sonographic findings of acute cholecystitis as follows:p was there any stone in gallbladder?p was there gallbladder wall thickening > 3 millimeters?p was there any fluid around the gallbladder?p was there any wall edema in the gallbladder? p are the ultrasound findings in favor of acute cholecystitis? then, patients were transferred to the radiology department to be examined (usually by a radiology resident under observation of a radiology attending physician) and the answer of mentioned questions were extracted from radiology department digital imaging and communications in medicine (dicom) system reports. emergency residents participating in this study were among the 3rd year emergency medicine residents who were trained in an hour-long theoretical class of ultrasound principles and knobology and 1-hour theoretical class of ruq ultrasound including reviews of both normal and pathologic anatomy videos. afterwards, they all had two hours of practice on a standard patient to have a hands-on practice. they did their first individual examination after 12 cases of direct supervision. patients and their companions were blind to the sonography findings. 2.4. data gathering patients’ demographic variables (age, sex) as well as sonographic findings of emergency and radiology departments regarding presence or absence of acute cholecystitis sonographic findings were collected using a predesigned checklist by a trained medical doctor. 2.5. statistical analysis data were analyzed using statistical package for social sciences (spss) software version 20. all quantitative data were reported as mean ± standard deviation and qualitative data as frequency and percentage. for measuring inter-rater agreement between radiology and emergency departments’ reports cohen’s kappa coefficient was calculated. in this study kappa coefficient < 0.20 was considered as poor, 0.21 0.40 as fair, 0.41 0.60 as moderate, 0.61 0.80 as good, and 0.81 1.00 as very good strength of agreement. screening performance characteristics of emergency department’s ruq sonography in diagnosis of acute cholecystitis were calculated using vassarstats medical software, considering radiology ward reports as standard test. 3. results 342 patients with the mean age of 53.92 ± 11.18 (20 – 83) years were studied (63.2% female). 179 (52.3%) ed sonographies were done by emergency physicians and 163 (47.7%) by trained 3rd year emergency medicine residents. 53 (15.50%) patients had at least one sonographic finding of acute cholecystitis based on ed reports, while radiology department reported the presence of these findings for 48 (14.00%) cases (kappa = 0.826). frequency of each sonographic finding in ed and radiology department reports is shown in table 1. the highest and lowest agreement between ed and radiology this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e11 table 1: frequency of each sonographic finding in emergency and radiology department reports finding department n (%) kappa emergency radiology gallstone 72 (21.1) 69 (20.2) 0.884 wall thickness>3mm 44 (12.9) 41 (12.0) 0.745 fluid around the gallbladder 22 (6.4) 22 (6.4) 0.660 wall edema 12 (3.5) 10 (2.9) 0.343 acute cholecystitis 53 (15.5) 48 (14.0) 0.826 table 2: screening performance characteristics of emergency department bedside sonography for 4 sonographic findings of acute cholecystitis characteristics gallstone wall edema fluid wall thickness true positive 64 4 15 33 false negative 5 6 7 8 false positive 8 8 7 11 true negative 265 324 313 290 sensitivity 92.7 (82.3-97.3) 40.0 (13.6-72.6) 68.2 (45.1-85.3) 75.0 (59.4-86.3) specificity 97.1 (94.1-98.6) 97.5 (95.1-98.9) 97.8 (95.3-99.0) 97.3 (94.6-98.7) positive predictive value 88.8 (78.7-94.7) 33.3 (11.3-64.6) 98.1 (45.1-85.3) 80.5 (64.6-90.6) negative predictive value 98.1 (95.5-99.3) 98.2 (95.999.3) 97.8 (95.3-99.0) 96.3 (93.4-98.1) positive likelihood ratio 8.0 (4.1-15.5) 0.5 (0.2-1.2) 2.1 (1.1-4.2) 4.1 (2.2-7.8) negative likelihood ratio 0.01 (0.007-0.04) 0.01 (0.008-0.04) 0.02 (0.01-0.04) 0.04 (0.02-0.06) departments were regarding the presence of stone (kappa: 0.884) and wall edema (kappa: 0.343), respectively. sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios of ed sonography for screening of cholecystitis were 89.58 (95%ci: 76.55 – 96.10), 96.59 (95%ci: 93.63 – 98.29), 81.13 (95%ci: 67.58 – 90.11), 98.26 (95%ci: 95.77 – 99.36), 4.30 (95%ci: 2.42 – 7.62) and 0.017 (95%ci: 0.007 – 0.041), respectively. table 2 summarizes the screening performance characteristics of ed bedside sonography for 4 sonographic findings of acute cholecystitis, separately. 4. discussion based on the findings of the present study, there was a very good agreement between ed and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. sensitivity and specificity of ed ruq sonography were 89.58 and 96.59, respectively. zenobi et al. in 2016 had their emphasis on murphy sign value in sonographic diagnosis of acute cholecystitis (15). kendall et al. estimated the sensitivity of 96% and specificity of 88% , for sonographic murphy sign in diagnosis of acute cholecystitis in an emergency setting (16). scruggs et al. conducted a study with a huge sample size of 1600 and calculated the sensitivity of 88% and the specificity of 84% for ruq bedside ultrasonography (17). some studies were focused on gallstones for diagnosis of acute cholecystitis (18, 19). based on our findings, there was a very good agreement between emergency and radiology departments regarding detection of gallstones. however, lower agreement in detecting some sonographic findings of cholecystitis such as gallbladder wall edema shows the necessity of continuous training in this regard. in point of care sonography the goal is finding an easy to do and easy to learn method without sacrificing the reliability. in 2009 gaspari et al., in an attempt to specify a learning curve for bedside ruq ultrasonography, concluded that after seven cases one will reach adequate image acquisition quality and technique and it will take around 25 cases to interpret the images reliably with a significant level of agreement with experts (20). in 2015 blehar et al. analyzing a database of 52,468 scans in most important fields of point of care ultrasound concluded that reaching the plateau may take 90 cases (21). however, we should note that in their graphs the level of agreement, sensitivity and specificity was already high from the beginning. our teaching method was really close to this study but combined with more hands-on sessions and a system of feedback after residents reported individually. producing a guideline for reaching competency in ruq ultrasound as a standard for evaluation and certification is recommended. 5. limitation the first limitation of this study was lack of a systematic image storing system; we had to export our data manually from our devices and it made the process more time-consuming. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. shekarchi et al. 4 lack of a gold standard as a scale for comparison was another problem. we don’t use hida scan in our centers, surgery is mostly done after passing the acute inflammatory phase, and computed tomography scan is used only in cases of suspected complications. 6. conclusion based on the findings of the present study, there was a very good agreement between ed and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. sensitivity and specificity of bedside ruq sonography were 89.58 and 96.59, respectively. yet, lower agreement in detecting some sonographic findings of acute cholecystitis such as gallbladder wall edema shows the necessity of continuous training in this regard. 7. appendix 7.1. acknowledgements the authors thank emergency departments of aja and iran university of medical sciences for facilities and technical assistance. the authors also gratefully acknowledge the cooperation of emergency medicine residents. 7.2. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. thistle jl, cleary pa, lachin jm, tyor mp, hersh t. the natural history of cholelithiasis: the national cooperative gallstone study. ann intern med. 1984;101(2):171-5. 2. friedman gd, raviola ca, fireman b. prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization. j clin epidemiol. 1989;42(2):127-36. 3. friedman gd. natural history of asymptomatic and symptomatic gallstones. am j surg. 1993;165(4):399-404. 4. trowbridge rl, rutkowski nk, shojania kg. does this patient have acute cholecystitis? jama. 2003;289(1):80-6. 5. miura f, takada t, strasberg sm, solomkin js, pitt ha, gouma dj, et al. tg13 flowchart for the management of acute cholangitis and cholecystitis. j hepatobiliary pancreat sci. 2013;20(1):47-54. 6. kalimi r, gecelter gr, caplin d, brickman m, tronco gt, love c, et al. diagnosis of acute cholecystitis: sensitivity of sonography, cholescintigraphy, and combined sonography-cholescintigraphy. j am coll surg. 2001;193(6):609-13. 7. watanabe y, nagayama m, okumura a, amoh y, katsube t, suga t, et al. mr imaging of acute biliary disorders. radiographics. 2007;27(2):477-95. 8. ralls pw, colletti pm, lapin sa, chandrasoma p, boswell wd, jr., ngo c, et al. real-time sonography in suspected acute cholecystitis. prospective evaluation of primary and secondary signs. radiology. 1985;155(3):767-71. 9. gore rm, yaghmai v, newmark gm, berlin jw, miller fh. imaging benign and malignant disease of the gallbladder. radiol clin north am. 2002;40(6):1307-23, vi. 10. angelico m, de santis a, capocaccia l. biliary sludge: a critical update. j clin gastroenterol. 1990;12(6):656-62. 11. cooperberg pl, burhenne hj. real-time ultrasonography. diagnostic technique of choice in calculous gallbladder disease. n engl j med. 1980;302(23):1277-9. 12. shea ja, berlin ja, escarce jj, clarke jr, kinosian bp, cabana md, et al. revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease. arch intern med. 1994;154(22):2573-81. 13. gillman lm, kirkpatrick aw. portable bedside ultrasound: the visual stethoscope of the 21st century. scand j trauma resusc emerg med. 2012;20:18. 14. kiewiet jj, leeuwenburgh mm, bipat s, bossuyt pm, stoker j, boermeester ma. a systematic review and metaanalysis of diagnostic performance of imaging in acute cholecystitis. radiology. 2012;264(3):708-20. 15. zenobii mf, accogli e, domanico a, arienti v. update on bedside ultrasound (us) diagnosis of acute cholecystitis (ac). intern emerg med. 2016;11(2):261-4. 16. kendall jl, shimp rj. performance and interpretation of focused right upper quadrant ultrasound by emergency physicians. j emerg med. 2001;21(1):7-13. 17. scruggs w, fox jc, potts b, zlidenny a, mcdonough j, anderson cl, et al. accuracy of ed bedside ultrasound for identification of gallstones: retrospective analysis of 575 studies. west j emerg med. 2008;9(1):1-5. 18. miller ah, pepe pe, brockman cr, delaney ka. ed ultrasound in hepatobiliary disease. j emerg med. 2006;30(1):69-74. 19. rowland jl, kuhn m, bonnin rl, davey mj, langlois sl. accuracy of emergency department bedside ultrasonography. emerg med (fremantle). 2001;13(3):305-13. 20. gaspari rj, dickman e, blehar d. learning curve of bedside ultrasound of the gallbladder. the journal of emergency medicine. 2009;37(1):51-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e11 21. blehar dj, barton b, gaspari rj. learning curves in emergency ultrasound education. academic emergency medicine. 2015;22(5):574-82. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e62 le t t e r to ed i to r the value of ultrasonography in determining pupillary light reflex in patients with traumatic ocular injuries; a letter to editor hamid mirjalili1, ali raee ezzabadi1∗, yeganeh yazdiyousefi1, mohammad ali jafari nadoshan1 1. emergency department, shahid sadoughi university of medical science, yazd, iran. received: july 2019; accepted: august 2019; published online: 10 november 2019 cite this article as: mirjalili h, raee ezzabadi a, yazdiyousefi y, jafari nadoshan m a. the value of ultrasonography in determining pupillary light reflex in patients with traumatic ocular injuries; a letter to editor. arch acad emerg med. 2019; 7(1): e62. pupillary light reflex (plr) measurement is one of the frequent physical examinations used by emergency physicians for assessment of brain stem function and monitoring of intracranial pressure (1, 2). plr could be abnormal due to various causes such as optic nerve damage, oculomotor nerve damage, brain stem lesion, and using central nervous system depressant drugs, such as barbiturates. direct plr measurement is not always possible in patients with ocular trauma suffering from hematoma, hyphema, and etc. one helpful tool for measuring plr in this situation is ultrasonography (3, 4). using a coronal ultrasonographic view of the iris upon contralateral stimulation with a penlight, ashot et al. emphasized that ultrasonography could be considered as a practical, fast and recordable method for evaluating plr (5). using consecutive sampling, the authors of this letter examined all head trauma patients suffering from unilateral ocular trauma, who visited the emergency departments of shahid sadooghi and shahid rahnemoun hospitals, yazd, iran, from 2017 to 2018 (ethics code: ir.ssu.medicine.rec.1396.265). patients with bilateral ocular trauma, penetrating trauma, history of any chronic disease (glaucoma, cataract, retina, etc.), or previous eye surgeries were excluded. using ezono 3000 ultrasound system and a linear probe with a 10 mhz frequency in coronal sections, plr was measured in both intact and injured eyes. the probe is fanned until the iris and pupil are visualized and a bright light is flashed (distance 1 cm). the pupil sizes for both intact and injured eyes were measured and registered through physical examination and ul∗corresponding author: ali raee ezzabadi; emergency department, shahid sadoughi hospital, shahid ghandy blvd., ebne sina ave., yazd, iran. tel: 00989131589448, email: ali.raee@gmail.com trasonography before and after flashing light to the eye, separately (plr in injured eye was measured using indirect light and light was flashed into the intact eye). then, the initial pupil size and plr were compared between physical and ultrasonography examinations (the study was performed on both conscious and unconscious patients). finally, 74 cases with the mean age of 20.30 ± 44.9 years were studied (87.8% male). in physical examination, patients’ pupillary response was unclear in 17 cases, light response occurred in 55 cases, and two patients didn’t exhibit pupillary response. however, examining the patients’ pupils through ultrasonography, the plr in one case was unclear and 62 individuals exhibited pupillary response, while 11 did not. there was a significant difference between physical examination and ultrasonography findings regarding the pupil size of injured eyes (2.82 ± 1.63 vs 3.58 ± 0.95, respectively; p = 0.001), while this was not observed in healthy eyes (3.55 ± 0.54 vs 3.50 ± 0.45, respectively; p = 0.065). it seems that, the use of ultrasound could be helpful in decreasing the number of unclear plr through accurate detection and measurement of pupil size in injured eyes. emergency physicians can consider ultrasonography as an accessible tool, complementary to physical examination for more accurate decision making in treatment of trauma patients. 1. appendix 1.1. acknowledgements this article is derived from the thesis of dr. hamid mirjalili to achieve his specialist degree in emergency medicine. 1.2. author’s contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. mirjalili et al. 2 authors orcids ali raee ezzabadi: 0000-0002-1545-1790 hamid mirjalili: 0000-0002-1268-0395 yeganeh yazdiyousefi: 0000-0002-2893-349x mohammad ali jafari nadoshan: 0000-0002-3171-6453 1.3. conflict of interest none. 1.4. funding and support none. references 1. park jc, moss he, mcanany jj. the pupillary light reflex in idiopathic intracranial hypertension. investigative ophthalmology & visual science. 2016;57(1):23-9. 2. szabadi e. functional organization of the sympathetic pathways controlling the pupil: light-inhibited and light-stimulated pathways. frontiers in neurology. 2018;9(1069). 3. blaivas m, theodoro d, sierzenski pr. a study of bedside ocular ultrasonography in the emergency department. academic emergency medicine. 2002;9(8):791-9. 4. blaivas m. bedside emergency department ultrasonography in the evaluation of ocular pathology. academic emergency medicine. 2000;7(8):947-50. 5. sargsyan ae, hamilton dr, melton sl, amponsah d, marshall ne, dulchavsky sajcuj. ultrasonic evaluation of pupillary light reflex. 2009;1(2):53-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 127 emergency (2015); 3 (4): 127-136 review article diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and meta-analysis mostafa hosseini1, 2, parisa ghelichkhani3, masoud baikpour4, abbas tafakhori5, 6, hadi asady7, mohammad javad haji ghanbari8, mahmoud yousefifard9*, saeed safari10 1. sina trauma and surgery research center, tehran university medical sciences, tehran, iran. 2. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 3. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 4. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 5. department of neurology, school of medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 6. iranian center of neurological research, tehran university of medical sciences, tehran, iran. 7. department of occupational health engineering, faculty of public health, tehran university of medical sciences, tehran, iran. 8. emergency medicine department, rasoul akram hospital, iran university of medical sciences, tehran, iran. 9. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. 10. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: mahmoud yousefifard, department of physiology, school of medicine, tehran university of medical sciences, poursina ave, tehran, iran. email: usefifard@razi.tums.ac.ir; phone/fax: +982122721155. received: june 2015; accepted: august 2015 abstract introduction: ultrasonography is currently being used as one of the diagnostic modalities in various medical emergencies for screening of trauma patients. the diagnostic value of this modality in detection of traumatic chest injuries has been evaluated by several studies but its diagnostic accuracy in diagnosis of pulmonary contusion is a matter of discussion. therefore, the present study aimed to determine the diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion through a systematic review and meta-analysis. methods: an extended systematic search was performed by two reviewers in databases of medline, embase, isi web of knowledge, scopus, cochrane library, and proquest. they extracted the data and assessed the quality of the studies. after summarization of data into true positive, false positive, true negative, and false negative meta-analysis was carried out via a mixed-effects binary regression model. further subgroup analysis was performed due to a significant heterogeneity between the studies. results: 12 studies were included in this meta-analysis (1681 chest trauma patients, 76% male). pooled sensitivity of ultrasonography in detection of pulmonary contusion was 0.92 (95% ci: 0.81-0.96; i2= 95.81, p<0.001) and its pooled specificity was calculated to be 0.89 (95% ci: 0.85-0.93; i2 = 67.29, p<0.001) while these figures for chest radiography were 0.44 (95% ci: 0.32-0.58; i2= 87.52, p<0.001) and 0.98 (95% ci: 0.88-1.0; i2= 95.22, p<0.001), respectively. subgroup analysis showed that the sources of heterogeneity between the studies were sampling method, operator, frequency of the transducer, and sample size. conclusion: ultrasonography was found to be a better screening tool in detection of pulmonary contusion. moreover, an ultrasonography performed by a radiologist / intensivist with 1-5mhz probe has a higher diagnostic value in identifying pulmonary contusions. key words: pulmonary contusion; ultrasonography; radiography; diagnostic tests, routine cite this article as: hosseini m, ghelichkhani p, baikpour m, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and meta-analysis. emergency. 2015;3(4):127-34. introduction: ulmonary contusion is a common complication of traumatic thoracic injuries. reports indicate that 25 to 80% of thoracic traumas are associated with pulmonary contusion (1, 2). various techniques have been proposed for detection of this lesion including clinical assessment, chest radiography (cxr), arterial blood gas, and computed tomography (ct) scan (3, 4). cxr is the most common diagnostic tool in detection of pulmonary contusion but presence of hemothorax or pneumothorax might complicate the diagnosis (5-7). moreover, identification of this lesion in cxr is not possible in the first 6 hours after injury (8, 9). ct scan is the most accurate diagnostic tool for pulmonary contusion and can detect the lesion right after the injury (10, 11). ultrasonography reported to have acceptable sensitivity p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 128 and specificity in detection of pulmonary contusion (1113). in the last 10 years many studies have evaluated the diagnostic values of ultrasonography and radiography in detection of traumatic thoracic injuries including pulmonary contusion (14-16), but reaching a consensus has been hindered by the vast disagreements on this subject. one of the ways to overcome this problem is conducting a systematic review and meta-analysis (17, 18). in this regard, we aimed to compare the diagnostic values of these two modalities in detection of pulmonary contusion through a meta-analysis of the available literature. methods: search strategy and selection criteria search strategy was based on the keywords related to ultrasonography and chest radiography including “ultrasonography” or “sonography” or “ultrasound” or “chest film” or “chest radiograph” combined with pulmonary contusion-related terms including “contusions” or “pulmonary contusion” or “lung contusion”. the systematic search was carried out in databases of medline (via pubmed), embase, isi web of knowledge, scopus, cochrane library, and proquest directed at finding retrospective and prospective original articles. we run a hand search using google scholar for extracting further studies. bibliographies of the related and review articles were scanned in order to find relevant undiscovered studies in our systematic search. the search keywords were extracted from medical subject heading (mesh) terms and emtree. review and editorial articles, case reports, letters to editors, poster presentations, and meeting abstracts were excluded from this survey. application of a reference test other than ct scan and conducting the study on animal samples were also considered as exclusion criteria. two reviewers (m.y, p.g) extracted data in true positive (tp), true negative (tn), false positive (fp), and false negative (fn). in cases where these values could not be obtained neither from the article nor by contacting the authors, the survey were excluded from the study. figure 1: flowchart of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 129 emergency (2015); 3 (4): 127-136 t a b le 1 : c h a re ct e ri st ic s o f in cl u d e d s tu d ie s s tu d y n o . o f p a ti e n t (+ / )1 a g e 2 (y e a r s ) m a le (% ) r e fe r e n c e / i n d e x t r a n s d u c e r / o p e r a to r s a m p li n g w e a k n e s s e s l ic h te n s te in 2 0 0 4 ( 1 9 ) 1 8 4 / 2 0 0 5 8 ± 1 5 n r c t / u s , c x r 5 m h z / in te n si v is t c o n se cu ti v e -- s o ld a ti 2 0 0 6 ( 1 1 ) 3 7 / 5 1 3 5 ( 1 8 -8 9 ) 7 2 .4 c t / u s , c x r 3 .5 to 5 -m h z / e p c o n se cu ti v e t h e m o st p a ti e n ts w e re a sse ss e d r e tr o sp e ct iv e ly e lm a li 2 0 0 7 ( 2 0 ) 3 9 / 2 1 4 3 ( 1 6 -8 5 ) 8 0 c t / c x r n a / r a d io lo g is t c o n se cu ti v e l o w s a m p le s iz e t r a u b 2 0 0 7 ( 2 1 ) 4 4 / 9 7 4 7 ( 1 8 -8 9 ) 7 5 c t / c x r n a / r a d io lo g is t c o n v e n ie n c e r e tr o sp e ct iv e d e si g n p o ss ib il it y o f se le ct io n b ia s r o c c o 2 0 0 8 ( 2 2 ) 6 3 / 1 1 7 4 2 ± 1 4 6 6 .7 c t / u s , c x r 3 .5 m h z / in te n si v is t c o n se cu ti v e l o w s a m p le s iz e x ir o u c h a k i 2 0 1 1 ( 1 3 ) 5 4 / 3 0 5 7 ± 2 1 .5 8 1 c t / u s , c x r 5 – to 9 -m h z / in te n si v is t c o n v e n ie n c e l o w s a m p le s iz e h y a c in th e 2 0 1 2 ( 2 3 ) 1 4 7 / 9 0 3 9 ( 2 2 -5 1 ) 8 2 c t / u s , c x r 5 -t o 2 -m h z / e p c o n se cu ti v e p o ss ib il it y o f se le ct io n b ia s b ła s iń s k a 2 0 1 3 ( 2 4 ) 1 1 / 4 9 n r n r c t / c x r n a / r a d io lo g is t c o n se cu ti v e l o w s a m p le s iz e c h a r d o li 2 0 1 3 ( 2 5 ) 1 1 / 1 8 9 3 8 ( 1 6 -9 0 ) 8 4 c t / c x r n a / e p c o n v e n ie n c e l a ck o f b li n d in g p o ss ib le s e le ct io n b ia s l e b la n c 2 0 1 4 ( 2 6 ) 3 8 / 7 3 6 ( 1 5 -5 6 ) 7 1 c t / u s , c x r 5 -t o 1 -m h z / in te n si v is t c o n v e n ie n c e l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s h e lm y 2 0 1 5 ( 2 7 ) 4 0 / 1 0 3 9 ( 1 8 -6 7 ) 7 0 c t / u s , c x r 5 m h z / r a d io lo g is t c o n v e n ie n c e l o w s a m p le s iz e p o ss ib il it y o f se le ct io n b ia s v a fa e i 2 0 1 5 ( 1 2 ) 4 8 / 1 0 4 3 1 ( 4 -6 7 ) 7 7 .6 c t / u s , c x r 3 .5 -t o 7 -m h z / e p c o n v e n ie n c e p o ss ib il it y o f se le ct io n b ia s 1 , ( + / ): ( n u m b e r o f p a ti e n t w it h c o n tu si o n / n u m b e r o f p a ti e n t w it h o u t co n tu si o n ); 2 , n u m b e r a re p re se n te d a s m e a n ± s ta n d a rd d e v ia ti o n o r (r a n g e ). c t : c o m p u te d t o m o g ra p h y ; c x r : c h e st r a d io g ra p h y ; e p : e m e rg e n cy p h y si ci a n ; n a : n o t a p p li ca b le ; n r : n o t r e p o rt e d ; u s : u lt ra so n o g ra p h y . this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 130 data extraction two reviewers (m.y, p.g) independently assessed the titles and abstracts of the articles found in the systematic search. then the full texts of the potentially relevant articles were evaluated and the data from the studies that met the inclusion criteria were precisely summarized in details. no time or language limitations were established. quality assessment of the articles was performed according to the guidelines suggested by 14-item quality assessment of diagnostic accuracy studies (quadas-2) tool (28). based on this criteria, all included studies were screened for presence of selection, performance, recording, and reporting biases. demographic characteristics of the patients including age, gender, the number of patients with/without pulmonary contusion according to the results of ct scans, characteristics of ultrasound device (transducer, frequency) and its operator, blinding status, and sampling method (consecutive, convenience). finally, the number of tp, tn, tn, and fn cases were recorded. disagreements were solved by the third author (m.h). the method proposed by sistrom and mergo (29) was used to extract the data presented as charts. web-based programs were utilized to calculate the number of tp, tn, tn, and fn cases from the articles in which only the sensitivity and specificity were presented. statistical analysis analysis was done by stata 11.0 statistical software via “midas” module. summary receiver operative curves (sroc), sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of ultrasonography and radiography in detection of pulmonary contusion with 95% confidence interval (95% ci) were estimated. in cases where data were presented separately for each hemi-thorax the information were included separately as presented in the original article. due to the significant heterogeneity between the included studies, mixed effects binary regression model was applied. heterogeneity was evaluated through calculation of i2 and χ2 tests and a p value of less than 0.1 along with an i2 greater than 50% were considered as presence of considerable heterogeneity (30). in order to recognize the sources of heterogeneity, subgroup analysis was performed considering the sampling method (consecutive/ convenience), operator (emergency physician/ other specialists) or the interpreting physician, the ultrasound device’s frequency of the transducer (1-5 mhz/ 5-10 mhz), and sample size (less than 100 patients/ more than 100 patients). in all the analyses, p value of less than 0.05 was considered as statistically significant. results: study characteristics search in the mentioned databases yielded 15 studies that met the inclusion criteria. further manual search resulted in finding 3 more related surveys. after summarization and quality assessment, 12 studies were included (11-13, 19-27) (figure 1). a total of 716 patients with pulmonary contusion and 965 subjects without were evaluated. their age ranged from 4 to 90 years old and male patients comprised 76% of the study population. the summary of included surveys is presented in table 1. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion were assessed simultaneously in eight studies (11-13, 19, 22, 23, 26, 27) and the accuracy of radiography was evaluated individually in four surveys (20, 21, 24, 25). considerable heterogeneity was observed between the studies (p<0.001). no publication bias was observed in evaluation of the diagnostic accuracy of ultrasonography (p = 0.97) and chest radiography (p = 0.15) (figure 2). meta-analysis ultrasonography area under the curve of sroc for ultrasonography in pulmonary contusion diagnosis was found to be 0.93 (95% ci: 0.91 0.95) (figure 3-a). pooled sensitivity of ultrasonography in this regard was 0.92 (95% ci: 0.81 0.96; i2 = 95.81, p < 0.001) and its pooled specificity was estimated to be 0.89 (95% ci: 0.85 0.93; i2 = 67.29, p < 0.001). ultrasonography had pooled positive and negative likelihood ratios of 8.94 (95% ci: 5.95 93.36; i2 = 67.92, p < 0.001) and 0.09 (95% ci: 0.04 0.22; i2 = 06.36, p < 0.001), respectively (figure 4). table 2 demonstrates the results of subgroup analysis. the sensitivity of this modality was lower when consecutive sampling method was used (0.87 vs. 0.97), procedure was performed via an emergency specialist (0.77 vs. 0.95), sample sizes of higher than 100 patients, the sensitivity (0.86 vs. 0.96), and frequencies of ultrasonography probe was higher than 5 mhz (0.86 vs. 0.93). chest radiography data from 12 surveys were included in this part of metaanalysis (11-13, 19-27). area under the sroc for radiography in detection of pulmonary contusion was 0.72 (95% ci: 0.67 0.75) (figure 3-b). pooled sensitivity and specificity of this diagnostic tool were 0.44 (95% ci: 0.32 0.58; i2= 87.52, p < 0.001) and 0.98 (95% ci: 0.88 1.0; i2 = 95.22, p < 0.001), respectively. pooled positive and negative likelihood ratios were also calculated to be 19.69 (95% ci: 3.59 108.07; i2 = 88.75, p < 0.001) and 0.57 (95% ci: 0.45 0.72; i2 = 93.13, p < 0.001), respectively (figure 5). subgroup analysis showed that the sensitivity of radiography is affected by the interpreting physician of the plain film (emergency physician/ other specialists) and sample size (table 2). according to the results of this analysis, the sensitivity of this imaging modality is higher when the radiographs were interpreted by a radiologist or intensivist (0.49; 95% ci: 0.30-0.68) compared to an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 131 emergency (2015); 3 (4): 127-136 t a b le 2 : s u b g ro u p a n a ly si s o f d ia g n o st ic a cc u ra cy f o r ch e st r a d io g ra p h y a n d u lt ra so n o g ra p h y i n d e te ct io n o f p u lm o n a ry c o n tu si o n c o v a r ia te n o . o f s tu d ie s b iv a r ia te r a n d o m -e ff e c t m o d e l s e n s it iv it y ( 9 5 % c i) p s p e c if ic it y ( 9 5 % c i) p h e te r o g e n e it y , i 2 p * u lt r a s o n o g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 5 0 .8 7 ( 0 .7 8 -0 .9 6 ) 0 .1 6 0 .9 0 ( 0 .8 6 -0 .9 5 ) < 0 .0 0 1 4 9 .0 % 0 .1 4 c o n v e n ie n c e 3 0 .9 7 ( 0 .9 4 -1 .0 0 ) 0 .8 8 ( 0 .8 2 -0 .9 5 ) o p e r a to r e m e rg e n cy p h y si ci a n 3 0 .7 7 ( 0 .6 2 -0 .9 3 ) < 0 .0 0 1 0 .9 0 ( 0 .8 4 -0 .9 5 ) < 0 .0 0 1 6 8 .0 % 0 .0 4 o th e r p h y si ci a n 5 0 .9 5 ( 0 .9 2 -0 .9 9 ) 0 .8 9 ( 0 .8 4 -0 .9 4 ) s a m p le s iz e < 1 0 0 4 0 .9 6 ( 0 .9 0 -1 .0 0 ) 0 .3 8 0 .9 4 ( 0 .8 9 -0 .9 9 ) < 0 .0 0 1 5 5 .0 % 0 .1 1 ≥ 1 0 0 4 0 .8 6 ( 0 .7 3 -0 .9 9 ) 0 .8 8 ( 0 .8 4 -0 .9 5 ) f r e q u e n c y 1 -5 m h z 5 0 .9 3 ( 0 .8 7 -1 .0 ) 0 .4 1 0 .8 8 ( 0 .8 4 -0 .9 1 ) < 0 .0 0 1 5 8 .0 % 0 .0 9 5 -1 0 m h z 3 0 .8 6 ( 0 .6 5 -1 .0 ) 0 .9 3 ( 0 .8 9 -0 .9 8 ) r a d io g r a p h y p a ti e n t e n r o ll m e n t c o n se cu ti v e 6 0 .4 5 ( 0 .2 6 -0 .6 3 ) 0 .9 0 0 .9 9 ( 0 .9 6 -1 .0 0 ) 0 .7 2 0 .0 % 0 .6 1 c o n v e n ie n c e 6 0 .4 4 ( 0 .2 4 -0 .6 3 ) 0 .9 5 ( 0 .8 5 -1 .0 0 ) o p e r a to r e m e rg e n cy p h y si ci a n 6 0 .4 0 ( 0 .2 1 -0 .5 8 ) 0 .7 4 0 .9 8 ( 0 .9 4 -1 .0 0 ) 0 .0 3 0 .0 % 0 .7 9 o th e r p h y si ci a n 6 0 .4 9 ( 0 .3 0 -0 .6 8 ) 0 .9 7 ( 0 .9 0 -1 .0 0 ) s a m p le s iz e < 1 0 0 6 0 .5 5 ( 0 .3 8 -0 .7 2 ) 0 .1 5 0 .9 4 ( 0 .8 2 -1 .0 0 ) 0 .9 9 3 6 .0 % 0 .2 1 ≥ 1 0 0 6 0 .3 5 ( 0 .1 9 -0 .5 1 ) 0 .9 9 ( 0 .9 7 -1 .0 0 ) *, p v a lu e < 0 .1 w a s co n si d e re d a s si g n if ic a n t fo r h e te ro g e n e it y ; c i: c o n fi d e n c e i n te rv a l. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 132 emergency specialist (0.40; 95% ci: 0.21 0.58). discussion: the present meta-analysis is the first to assess the diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion. the results illustrate a higher sensitivity of ultrasonography compared to radiography (0.92 vs. 0.44) in this regard, whereas the specificity of radiography was slightly higher (0.97 vs. 0.89). since these two imaging modalities are the first diagnostic tools for assessment of traumatic thoracic injuries, their screening accuracy is of utmost importance. accordingly, ultrasonography has better screening performance characteristics in detection of pulmonary contusion compared to radiography. various studies have pointed out the fact that diagnostic accuracy of ultrasonography is directly dependent on the skills of the operator (14, 15, 31, 32). findings of the present survey were also congruent with this statement to some extent. the results demonstrated a higher sensitivity of ultrasonography in detection of pulmonary contusion when performed by a radiologist or an intensivist compared to emergency specialists. this might be due to the nature of pulmonary contusion whose diagnostic signs are very challenging to detect. the most important signs of pulmonary contusion identified by ultrasonography include multiple b-lines and an irregularly delineated tissue image which might be a moderately hypo-echoic blurred lesion (16). furthermore, after observation of these signs, the operator should rule out pneumothorax as well. therefore, experience plays an important role in pulmonary contusion diagnosis. frequency of transducer was another factor affecting the diagnostic accuracy of ultrasonography. application of transducers with frequencies lower than 5mhz yield greater diagnostic values compared to higher. this finding is also related to the nature of the lesion. contusion in characterized by parenchymal injuries and accumulation of fluid and blood in the lung tissues (16). these tissues lie in the deepest layers of chest cavity and so the penetrating power of ultrasound wave is more important than the image resolution (which is directly related to the wave’s frequency). since ultrasound waves with lower frequencies have greater penetrating powers, application of these probes increases the chances of pulmonary contusion diagnosis. sample size was also found to have an effect on diagnostic values of ultrasonography and radiography in detection of pulmonary contusion. the sensitivity of both these modalities was found to be higher in the studies with sample sizes of less than 100 patients. this might be due to possible selection bias in these studies (33). selection of patients with severe traumas and so the higher chances of injury identification via imaging would be prominent in these studies. moreover in some of these surveys, pneumothorax patients had been excluded which might have made the diagnosis easier (27). utilization of three strategies has improved the quality of the present meta-analysis. firstly, comprehensive search in databases to include the maximum number of related surveys and secondly, elimination of publication bias. thirdly, the effects of heterogeneity between the studies were controlled by subgroup analysis. on the other hand, simultaneous inclusion of retrospective and prospective studies might be considered as a limitation of this study. however, evaluation of outliers on the scatterplot based on standardized predictive random effects revealed that retrospective surveys are not the cause of diversity between the studies. moreover, due to the observational nature of included studies, precise assessment of causal relationships was impossible. conclusion: the results of present meta-analysis revealed the better screening performance characteristics of chest ultrasonography compared to radiography in detection of pulmonary contusion. it should be mentioned that these characteristics where dependent on operator and characteristics of device. acknowledgments: none conflict of interest: none funding support: this research has been supported by tehran university of medical sciences & health services grant number: 9302-38-25618. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the 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chin j traumatol. 2013;16(6):351-4. 26. leblanc d, bouvet c, degiovanni f, et al. early lung ultrasonography predicts the occurrence of acute respiratory distress syndrome in blunt trauma patients. intensive care med. 2014;40(10):1468-74. 27. helmy s, beshay b, hady ma, mansour a. role of chest ultrasonography in the diagnosis of lung contusion. egypt j chest dis tuberc. 2015;64:469–75. 28. whiting pf, rutjes aw, westwood me, et al. quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies. ann intern med. 2011;155(8):529-36. 29. sistrom cl, mergo pj. a simple method for obtaining original data from published graphs and plots. am j roentgenol. 2000;174(5):1241-4. 30. higgins jp, thompson sg, deeks jj, altman dg. measuring inconsistency in meta-analyses. bmj. 2003;327(7414):557. 31. abbasi s, farsi d, hafezimoghadam p, fathi m, zare ma. accuracy of emergency physician-performed ultrasound in detecting traumatic pneumothorax after a 2-h training course. eur j emerg med. 2013;20(3):173-7. 32. lee jh, jeong yk, park kb, park jk, jeong ak, hwang jc. operator-dependent techniques for graded compression sonography to detect the appendix and diagnose acute appendicitis. am j roentgenol. 2005;184(1):91-7. 33. deeks jj, macaskill p, irwig l. the performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. j clin epidemiol. 2005;58(9):882-93. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 134 a b figure 2: deeks’ funnel plot asymmetry test for assessment of publication bias. p values < 0.05 were considered as significant. ultrasonography (a); radiography (b). ess: effective sample sizes. a b figure 3: summary receiver operative curves (sroc) with prediction and confidence contours of ultrasonography (a) and chest radiography (b) in detection of pulmonary contusion. auc: area under the curve; sens: sensitivity; spec: specificity. 1 2 3 4 5 6 7 8.05 .1 .15 .2 1 /r o ot (e ss ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.97 1 2 3 4 5 6 7 8 9 10 11 12.05 .1 .15 .2 1 /r o o t( e ss ) 1 10 100 1000 diagnostic odds ratio study regression line deeks' funnel plot asymmetry test pvalue = 0.15 1 2 3 4 5 6 7 8 0.0 0.5 1.0 se n si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.92 [0.81 0.96] spec = 0.89 [0.85 0.93] sroc curve auc = 0.93 [0.91 0.95] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours 1 2 3 4 5 6 7 8 9 10 11 12 0.0 0.5 1.0 s en si ti v it y 0.00.51.0 specificity observed data summary operating point sens = 0.44 [0.32 0.58] spec = 0.98 [0.88 1.00] sroc curve auc = 0.72 [0.67 0.75] 95% confidence contour 95% prediction contour sroc with prediction & confidence contours this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 135 emergency (2015); 3 (4): 127-136 a b figure 4: forest plot of screening performance characteristics of chest ultrasonography in detection of pulmonary contusion. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q =167.02, df = 7.00, p = 0.00 i2 = 95.81 [94.03 97.59] 0.92[0.81 0.96] 0.69 [0.54 0.81] 0.98 [0.87 1.00] 0.92 [0.79 0.98] 0.61 [0.53 0.69] 0.94 [0.85 0.99] 0.89 [0.78 0.95] 0.95 [0.82 0.99] 0.98 [0.95 1.00]0.98 [0.95 1.00] author / year combined vafaei 2015 helmy 2015 leblanc 2014 hyacinthe 2012 xirouchaki 2011 rocco 2008 soldati 2006 lichtenstein 2004 0.5 1.0 specificity (95% ci) q = 21.40, df = 7.00, p = 0.00 i2 = 67.29 [42.90 91.69] 0.89[0.85 0.93] 0.92 [0.85 0.97] 0.90 [0.55 1.00] 0.86 [0.42 1.00] 0.80 [0.70 0.88] 0.93 [0.78 0.99] 0.89 [0.82 0.94] 0.96 [0.87 1.00] 0.88 [0.83 0.92]0.88 [0.83 0.92] author / year combined vafaei 2015 helmy 2015 leblanc 2014 hyacinthe 2012 xirouchaki 2011 rocco 2008 soldati 2006 lichtenstein 2004 0.4 1.0 dlr positive (95% ci) q = 36.16, df = 7.00, p = 0.00 i2 = 67.92 [67.92 93.36] 8.64[5.95 12.55] 8.94 [4.47 17.86] 9.75 [1.52 62.63] 6.45 [1.05 39.67] 3.06 [1.99 4.72] 14.17 [3.71 54.13] 8.00 [4.76 13.45] 24.12 [6.19 94.04] 8.20 [5.63 11.94]8.20 [5.63 11.94] author / year combined vafaei 2015 helmy 2015 leblanc 2014 hyacinthe 2012 xirouchaki 2011 rocco 2008 soldati 2006 lichtenstein 2004 1.0 94.0 dlr negative (95% ci) q =192.42, df = 7.00, p = 0.00 i2 = 96.36 [94.89 97.84] 0.09[0.04 0.22] 0.34 [0.22 0.52] 0.03 [0.01 0.19] 0.09 [0.03 0.28] 0.48 [0.39 0.61] 0.06 [0.02 0.18] 0.13 [0.06 0.25] 0.06 [0.01 0.22] 0.02 [0.01 0.06]0.02 [0.01 0.06] author / year combined vafaei 2015 helmy 2015 leblanc 2014 hyacinthe 2012 xirouchaki 2011 rocco 2008 soldati 2006 lichtenstein 2004 0 1 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hosseini et al 136 a b figure 5: forest plot of screening performance characteristics of chest radiography in detection of pulmonary contusion. sensitivity and specificity (a); diagnostic likelihood ratio (dlr) (b). ci: confidence interval. sensitivity (95% ci) q = 87.52, df = 11.00, p = 0.00 i2 = 87.43 [81.52 93.34] 0.44[0.32 0.58] 0.44 [0.29 0.59] 0.40 [0.25 0.57] 0.79 [0.63 0.90] 0.00 [0.00 0.28] 0.73 [0.39 0.94] 0.29 [0.22 0.37] 0.46 [0.33 0.60] 0.24 [0.14 0.36] 0.52 [0.37 0.68] 0.69 [0.52 0.83] 0.27 [0.14 0.44] 0.60 [0.52 0.67]0.60 [0.52 0.67] author / year combined vafaei 2015 helmy 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 xirouchaki 2011 rocco 2008 traub 2007 elmali 2007 soldati 2006 lichtenstein 2004 0.0 0.9 specificity (95% ci) q =230.14, df = 11.00, p = 0.00 i2 = 95.22 [93.53 96.91] 0.98[0.88 1.00] 0.73 [0.63 0.81] 0.90 [0.55 1.00] 0.43 [0.10 0.82] 1.00 [0.98 1.00] 1.00 [0.93 1.00] 0.94 [0.88 0.98] 0.80 [0.61 0.92] 0.97 [0.91 0.99] 1.00 [0.96 1.00] 0.76 [0.53 0.92] 1.00 [0.93 1.00] 1.00 [0.98 1.00]1.00 [0.98 1.00] author / year combined vafaei 2015 helmy 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 xirouchaki 2011 rocco 2008 traub 2007 elmali 2007 soldati 2006 lichtenstein 2004 0.1 1.0 dlr positive (95% ci) q =138.09, df = 11.00, p = 0.00 i2 = 88.75 [88.75 95.32] 19.69[3.59 108.07] 1.62 [1.04 2.55] 4.00 [0.60 26.68] 1.38 [0.71 2.68] 15.83 [0.33 763.86] 70.83 [4.39 1000] 5.27 [2.17 12.80] 2.31 [1.07 5.01] 6.96 [2.41 20.09] 102.36 [6.36 1000] 2.91 [1.32 6.43] 28.74 [1.74 475.43] 240.11 [15.03 1000]240.11 [15.03 1000] author / year combined vafaei 2015 helmy 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 xirouchaki 2011 rocco 2008 traub 2007 elmali 2007 soldati 2006 lichtenstein 2004 0.3 1000.0 dlr negative (95% ci) q =160.00, df = 11.00, p = 0.00 i2 = 93.13 [90.41 95.84] 0.57[0.45 0.72] 0.77 [0.58 1.00] 0.67 [0.48 0.92] 0.49 [0.17 1.00] 0.96 [0.85 1.00] 0.29 [0.12 0.71] 0.75 [0.67 0.84] 0.67 [0.49 0.91] 0.79 [0.68 0.91] 0.48 [0.35 0.65] 0.40 [0.24 0.68] 0.73 [0.60 0.89] 0.40 [0.34 0.48]0.40 [0.34 0.48] author / year combined vafaei 2015 helmy 2015 leblanc 2014 chardoli 2013 blasinska 2013 hyacinthe 2012 xirouchaki 2011 rocco 2008 traub 2007 elmali 2007 soldati 2006 lichtenstein 2004 0 1 introduction: methods: search strategy and selection criteria data extraction statistical analysis results: study characteristics meta-analysis discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: emergency. 2018; 6 (1): e2 or i g i n a l re s e a rc h urinary neutrophil gelatinase-associated lipocalin (ngal) and cystatin c in early detection of pediatric acute kidney injury; a diagnostic accuracy study neamatollah ataei1,2, sonbol ameli1,2, mahmoud yousefifard3, alireza oraei4, fatemeh ataei5, behnaz bazargani1,2, arash abbasi1,2, mostafa hosseini6∗ 1. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 2. department of pediatric nephrology, children’s hospital medical center, tehran university of medical sciences, tehran, iran. 3. physiology research center and department of physiology, faculty of medicine, iran university of medical sciences, tehran, iran. 4. department of medicine, school of medicine, tehran university of medical sciences, tehran, iran. 5. department of nuclear medicine, department of nuclear medicine, valiasr hospital, zanjan university of medical sciences, zanjan, iran. 6. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: july 2017; accepted: november 2017; published online: 12 january 2018 abstract: introduction: there is a controversy regarding accuracy of neutrophil gelatinase-associated lipocalin (ngal) and cystatin c in early detection of acute kidney injury (aki). the present study aimed to compare the diagnostic value of two biomarkers in this regard. methods: in the present diagnostic accuracy study, all children between the ages of 1 month to 14 years were entered. pediatric risk, injury failure, loss, end-stage renal disease (prifle) criteria was used for identification of children with aki as the reference test. blood samples were taken from all patients at baseline and 48 hours after admission to assess serum creatinine and cystatin c level. in addition, a urine sample was obtained within 6 hours of admission in order to measure ngal level. in the end, area under the receiving operating characteristics (roc) curve, sensitivity, and specificity of urine ngal (ungal) and cystatin c in early detection of aki were compared. results: data from 96 children with the mean age of 27.31±36.24 months were entered (56.25% girls). area under the roc curve of ungal level in diagnosis of aki in children was 0.91 (95% ci: 0.80 to 1.00) and area under the roc of cystatin c was 0.90 (95% ci: 0.77 to 1.00). both tests had the same value in diagnosis of aki (p=0.89). the best cut-off point of ungal for diagnosing aki was 125 mg/l. ungal had a sensitivity and specificity of 0.92 (0.62 to 0.99) and 0.69 (0.57 to 0.78), respectively. the best cut-off point of serum cystatin c level was 0.4 mg/l. cystatin c had a sensitivity and specificity of 0.92 (0.62 to 0.99) and 0.64 (0.52 to 0.74), respectively. conclusion: the present study showed that ungal level has the same value as serum cystatin c level in early diagnosis of aki. keywords: cystatin c; lipocalin-2; acute kidney injury; early diagnosis; dimensional measurement accuracy © copyright (2018) shahid beheshti university of medical sciences cite this article as: ataei n, ameli s, yousefifard m, oraei a, ataei f, bazargani b, abbasi a, hosseini m. urinary neutrophil gelatinaseassociated lipocalin (ngal) and cystatin c in early detection of pediatric acute kidney injury; a diagnostic accuracy study. emergency. 2018; 6(1): e2. ∗corresponding author: mostafa hosseini; department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127. 1. introduction a cute kidney injury (aki) is considered an important issue that if not promptly managed can lead to serious complications such as chronic kidney disease, end-stage renal diseases and even death (1-3). recent studies show that preventive strategies can significantly reduce the burden of the disease (4) and early diagnosis and treatment of aki can significantly decrease medical costs. unforthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. ataei et al. 2 tunately kidney diseases are asymptomatic most of the time and disease manifestations do not occur until a large amount of renal tissue is destroyed (5). hence, the best suggestion is that nephrologists and physicians of other specialties begin to comprehend the importance of early diagnosis of kidney disease. several diagnostic methods are introduced for identification of children with aki, but none of them could accurately predict the outcome of disease in the initial stages (6). over the past decade, many studies have shown that multiple serum and urine biomarkers are useful for early detection of kidney injury and have a better prognostic role than previous diagnostic tools (7-9). after three meta-analyses we reached a conclusion indicating that biomarkers such as neutrophil gelatinase-associated lipocalin (ngal) and cystatin c are accurate predictors of aki (10-12). however, it is yet to be studied which one of these biomarkers and their sources (serum or urine) have greater value in prediction of aki. a metaanalysis reported that serum cystatin c has a greater diagnostic value in detection of aki in children and adolescents than its urine level (10). existing evidence regarding ngal is however inconclusive and further research needs to be carried out (13-15). the present study aimed to assess the value of urinary ngal (ungal) and serum cystatin c in early diagnosis of hospitalized children with aki. 2. methods 2.1. study design and setting in the present diagnostic accuracy study, the value of urine ngal in early detection of pediatric aki was assessed. all children brought to children’s medical center of tehran, iran, between 2015 and 2016 were entered in a prospective manner. the protocol of the present study was approved by the ethics committee of tehran university of medical sciences and all researchers adhered to the principles of the helsinki declaration during the study period. additionally, a consent form was obtained from patients or their parents. 2.2. participants the study population of the present study consisted of all children between the ages of 1 month and 14 years, who were suspected to aki according to their in-charge physician’s opinion. exclusion criteria were children with chronic kidney disease, need for renal replacement therapy and those not giving consent. convenience sampling was used in the present study. 2.3. test methods blood samples were taken from all patients on admission and 48 hours after admission and were sent to the laboratory of children’s medical center in order to assess serum creatinine and cystatin c level. creatinine measurement was done using jaffe method, a spectrophotometry kit and a hitachi 717 device. additionally, serum cystatin c was measured using cystatin c elisa kit from bioporto diagnostic of denmark using sandwich elisa method. glomerular filtration rate (gfr) was calculated based on cystatin c formula (16). a urine sample was obtained within 6 hours of admission and was stored in -80◦c after centrifuge. measurement of ungal was done using an ngal elisa kit from bioporto diagnostics, denmark using sandwich elisa method. in addition, the laboratory and technicians who entered data were not aware of the aki status of patients. index test was assessed in a blind manner as ungal measurement was performed before gfr calculation. 2.4. outcome aki was considered as the endpoint of the study. pediatric risk, injury failure, loss, end-stage renal disease (prifle) criteria was used for identification of children with aki as the reference test (17). therefore, a decrease in estimated creatinine clearance by at least 25% from baseline within 48 hours after admission was considered the definition of aki. 2.5. statistical analysis the required sample size was estimated based on the suggested method of hajian-tilaki (18). a sensitivity of 93% for ungal in diagnosis of aki and a minimum marginal error of 0.1 (19) were considered in calculating the sample size hence, 91 patients were required. in the end, data from 96 patients were entered and analyzed. data were analyzed using stata 11.0. patients were divided to two groups of aki and no-aki based on their gfr level within 48 hours of admission. at the end, area under the receiving operating characteristics (roc) curve, sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive and negative likelihood ratios of ungal and cystatin c were calculated in order to assess their discriminatory power with a 95% confidence interval (ci). areas under the curve of the two biomarkers were compared using the method suggested by cleves and rock (20). general calibration was assessed by drawing calibration plot, which showed that the perfect calibration was the reference line with an intercept of zero and slope of 1. as the slope and intercept of calibration plot of models become closer to 1 and zero, respectively, they will be considered more perfect in prediction of aki. additionally, overall performance was calculated using brier score in order to assess the predictive accuracy and predictive reliability. a p value of less than 0.05 was considered significant in all analyses. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e2 table 1: summary of demographic, baseline, and laboratory values based on outcome variable no-aki (n = 83) aki (n = 13) total (n = 96) p sex (n, %) boy 47 (56.63) 7 (53.85) 54 (56.25) 0.85 girl 36 (43.37) 6 (46.15) 42 (43.75) age (month) 28.66±37.58 18.69±25.58 27.31±36.24 0.64* etiology of aki pneumonia 7 (8.43) 0 (0.0) 7 (7.29) 0.24# cardiac diseases 14 (16.87) 3 (23.08) 17 (17.71) trauma 3 (3.61) 0 (0.0) 3 (3.13) sepsis 4 (4.82) 2 (15.38) 6 (6.25) urologic disorders 21 (25.30) 2 (15.38) 23 (23.96) pulmonary 14 (16.87) 2 (15.38) 16 (16.67) liver diseases 6 (7.23) 2 (15.38) 8 (8.33) metabolic disorders 3 (3.61) 2 (15.38) 5 (5.21) other 11 (13.25) 0 (0.0) 11 (11.46) height (cm) 76.48±25.30 72.08±21.55 75.88±24.75 0.63* cystatin c on admission (mg/l) 0.35±0.45 1.97±1.10 0.57±0.80 < 0.0001* ungal (mg/l) 168.59±284.52 1929.92±3957.54 407.10±1554.12 < 0.0001* creatinine (mg/l) baseline 0.48±0.16 0.49±0.16 0.49±0.16 0.61* 48 hours 0.44±0.14 1.08±0.36 0.53±0.28 < 0.0001* ecci (ml/min/ 1.73 m2) baseline 91.36±37.24 34.46±10.84 83.66±39.94 0.61* 48 hours 91.36±37.24 34.46±10.84 83.66±39.94 < 0.0001* aki: acute kidney injury; ecci: estimated creatinine clearance by cystatin c equation; ungal: urinary neutrophil gelatinase-associated lipocalin. *, based on mann-whitney u test; #, based on fisher’s exact test. table 2: screening performance characteristics of urinary neutrophil gelatinase-associated lipocalin (ungal) and cystatin c in detection of acute kidney injury (aki) performance cystatin c ungal cut off 0.4 mg/l 125 mg/l true positive 12 12 true negative 53 57 false positive 30 26 false negative 1 1 sensitivity 0.92 (0.62 to 0.99) 0.92 (0.62 to 0.99) specificity 0.64 (0.52 to 0.74) 0.69 (0.57 to 0.78) positive predictive value 0.29 (0.16 to 0.45) 0.32 (0.18 to 0.49) negative predictive value 0.98 (0.89 to 1.0) 0.98 (0.89 to 1.0) positive likelihood ratio 2.55 (1.84 to 3.54) 2.95 (2.07 to 4.20) negative likelihood ratio 0.12 (0.02 to 0.80) 0.11 (0.02 to 0.74) *, data are presented as estimated value and 95% confidence interval. 3. results 3.1. baseline characteristics data from 96 children with the average age of 27.31±36.24 months (ranging from 1 month to 156 months) were entered (56.25% boys). urologic problems (26.96%) were the most common etiology for aki. due to prifle criteria, 13 cases (13.54%) of aki were identified. the ungal level in aki group (1929.92±3957.54) was significantly higher than no-aki group (168.59±284.52) with a p value of less than 0.0001. similar results were observed regarding cystatin c levels (1.97±1.10 vs. 0.35±0.45; p < 0.0001) (table 1). area under the roc of urine ngal level in diagnosis of aki in children was 0.91 (95% ci: 0.80 to 1.00) and area under the roc of cystatin c was 0.90 (95% ci: 0.77 to 1.00). both tests had the same value in diagnosis of aki (p=0.89) (figure 1). both biomarkers had appropriate calibration levels. the slope of calibration line for ungal and cystatin c were 1.02 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. ataei et al. 4 figure 1: comparison of the areas under the receiver operating characteristics (roc) curve of urinary neutrophil gelatinase associated lipocalin (ungal) and serum cystatin c level in diagnosis of acute kidney injury in children within 48 hours of admission. and 1.001, respectively. the calculated intercept of the mentioned biomarkers were -0.006 and -0.0006, respectively. additionally, brier score of ungal and cystatin c were 0.07 and 0.08, respectively, which showed good overall performance of both biomarkers in diagnosis of aki in children (figure 2). the best cut-off point of ungal for diagnosis aki was 125 mg/l. ungal had a sensitivity and specificity of 0.92 and 0.69, respectively at this level. ungal level had a ppv and npv of 0.32 and 0.98, respectively. the best cut-off point of serum cystatin c level was 0.4 mg/l. cystatin c had a sensitivity and specificity of 0.92 and 0.64, respectively at the mentioned cut-off point. additionally, cystatin c had a ppv and npv of 0.28 and 0.98, respectively (table 2). 4. discussion the present study showed that ungal and serum cystatin c level are reliable biomarkers for early detection of pediatric aki. level of these biomarkers measured early after injury can identify aki much sooner than conventional methods. ngal is a 20 kda protein expressed in renal tubules which is released into the urine in case of acute or chronic kidney injury. therefore, ungal level might reflect kidney injury. faster increase in ungal level compared to serum creatinine level in response to aki is one of its benefits over creatinine. however, some biomarkers such as serum creatinine level indicate renal function and are indirectly indicative of aki (21). in other words, gfr should decrease to a certain level in order to disturb creatinine clearance and increase its serum level, which is required for diagnosis of aki. however, ngal level increases in urine in response to kidney injury; hence, it can be a better marker of the severity of aki (22). in a meta-analysis of 37 studies by researchers of the present study, it was reported that assessing ungal level within the first 6 hours of admission can accurately predict the incidence of acute kidney injury in children in the first 48 hours (12). similar results were found in another metaanalysis on serum ngal level. however, the best window period for measuring serum ngal level was reported to be within the first 12 hours of admission (11). due to the mentioned findings, ungal level seems to have a better performance in prediction of aki. cystatin c is another biomarker, the predictive value of which was proven in the present study. similarly, a meta-analysis showed that serum cystatin c level has a reasonably good value in predicting aki in children. additionally, serum cystatin c level has a greater value compared to its urine level (10). hence, serum cystatin c level was used in the present study. for the first time, the present study showed that ungal and serum cystatin c level have similar values in prediction of aki in children. 5. limitation small sample size is one of the limitations of the present study. in the present small sized study, patients brought to an individual center were assessed and selection bias might be present as convenience sampling was used. short follow-up period (48 hours) was another limitation of this study. additionally, misclassifications might be present as a small number of patients show signs and symptoms of aki (based on prifle criteria) after the first 48 hours (during the first week of admission or even later). 6. conclusion the present study showed that both ungal and serum cystatin c level are highly valuable predictors of aki within the first hours of admission. in other words, level of these biomarkers measured early after injury can identify aki much sooner than conventional methods. additionally, ungal seems to be a better biomarker in children and adolescents as its assessment is less invasive than assessing serum cystatin c level and can be measured using a single urine sample. 7. appendix 7.1. acknowledgements none. 7.2. author contribution mostafa hosseini, mahmoud yousefifard and neamatollah ataei designed the study. sonbol ameli, behnaz bazargani and arash abbasi participated in acquisition of data. mostafa hosseini analyzed the data. fatemeh ataei and alireza oraei this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e2 figure 2: calibration plot of urinary neutrophil gelatinase-associated lipocalin (ungal) and cystatin c in detection of acute kidney injury (aki). participate in management of data. mahmoud yousefifard and alireza oraei wrote the first draft and other revising manuscript critically. all authors approved final version of the manuscript to be published and are accountable for all aspects of the work. 7.3. funding/support this research has been supported by tehran university of medical sciences & health services grant number: 94-03184-30338. 7.4. conflict of interest the authors declare no conflicts of interest. references 1. anavekar ns, mcmurray jj, velazquez ej, solomon sd, kober l, rouleau j-l, et al. relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. new england journal of medicine. 2004;351(13):1285-95. 2. wang c, lv ls, huang h, guan j, ye z, li s, et al. initiation time of renal replacement therapy on patients with acute kidney injury: a systematic review and metaanalysis of 8179 participants. nephrology (carlton, vic). 2017;22(1):7-18. 3. jha v, garcia-garcia g, iseki k, li z, naicker s, plattner b, et al. chronic kidney disease: global dimension and perspectives. the lancet. 2013;382(9888):260-72. 4. du y, zappitelli m, mian a, bennett m, ma q, devarajan p, et al. urinary biomarkers to detect acute kidney injury in the pediatric emergency center. pediatric nephrology. 2011;26(2):267-74. 5. parikh cr, devarajan p, zappitelli m, sint k, thiessenphilbrook h, li s, et al. postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. journal of the american society of nephrology. 2011;22(9):1737-47. 6. chobanian av, bakris gl, black hr, cushman wc, green la, izzo jr jl, et al. the seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the jnc 7 report. jama. 2003;289(19):2560-71. 7. mitsnefes mm, kathman ts, mishra j, kartal j, khoury pr, nickolas tl, et al. serum neutrophil gelatinaseassociated lipocalin as a marker of renal function in children with chronic kidney disease. pediatric nephrology. 2007;22(1):101-8. 8. mishra j, dent c, tarabishi r, mitsnefes mm, ma q, kelly c, et al. neutrophil gelatinase-associated lipocalin (ngal) as a biomarker for acute renal injury after cardiac surgery. the lancet. 2005;365(9466):1231-8. 9. nickolas tl, barasch j, devarajan p. biomarkers in acute and chronic kidney disease. current opinion in nephrology and hypertension. 2008;17(2):127-32. 10. nakhjavan-shahraki b, yousefifard m, ataei n, baikpour m, ataei f, bazargani b, et al. accuracy of cystatin c in prediction of acute kidney injury in children; serum or urine levels: which one works better? a systematic review and meta-analysis. bmc nephrology. 2017;18(1):120. 11. izadi a, yousefifard m, nakhjavan-shahraki b, baikpour m, mirzay razaz j, ataei n, et al. value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury; a systematic review and meta-analysis. international journal of pediatrics. 2016;4(11):3815-36. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. ataei et al. 6 12. izadi a, yousefifard m, nakhjavan-shahraki b, baikpour m, mirzay razaz j, hosseini m. diagnostic value of urinary neutrophil gelatinase-associated lipocalin (ngal) in detection of pediatric acute kidney injury; a systematic review and meta-analysis. international journal of pediatrics. 2016;4(11):3875-95. 13. devarajan p, m barasch j. neutrophil gelatinaseassociated lipocalin (ngal) as a biomarker for acute kidney injury. recent patents on biomarkers. 2012;2(3):179-89. 14. wagener g, jan m, kim m, mori k, barasch jm, sladen rn, et al. association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. anesthesiology-philadelphia then hagerstown-. 2006;105(3):485. 15. wagener g, gubitosa g, wang s, borregaard n, kim m, lee ht. urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. american journal of kidney diseases. 2008;52(3):425-33. 16. laterza of, price cp, scott mg. cystatin c: an improved estimator of glomerular filtration rate? clinical chemistry. 2002;48(5):699-707. 17. soler ya, nieves-plaza m, prieto m, garcia-de jesus r, suarez-rivera m. prifle (pediatric risk, injury, failure, loss, end stage renal disease) score identifies acute kidney injury and predicts mortality in critically ill children : a prospective study. pediatric critical care medicine : a journal of the society of critical care medicine and the world federation of pediatric intensive and critical care societies. 2013;14(4):e189-e95. 18. hajian-tilaki k. sample size estimation in diagnostic test studies of biomedical informatics. journal of biomedical informatics. 2014;48:193-204. 19. nickolas tl, o’rourke mj, yang j, sise me, canetta pa, barasch n, et al. sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. annals of internal medicine. 2008;148(11):810-9. 20. cleves ma, rock l. from the help desk: comparing areas under receiver operating characteristic curves from two or more probit or logit models. the stata journal. 2002;2(3):301-13. 21. askenazi dj, ambalavanan n, goldstein sl. acute kidney injury in critically ill newborns: what do we know? what do we need to learn? pediatric nephrology. 2009;24(2):265-74. 22. haase m, bellomo r, devarajan p, haase-fielitz a. neutrophil gelatinase-associated lipocalin (ngal) in acute kidney injury: a systematic review and meta-analysis. intensive care medicine. 2009;35:s215. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 16 emergency (2015); 3 (1): 16-21 original research the most important causes of death in iranian population; a retrospective cohort study soheil saadat1, mahmoud yousefifard2, hadi asady3, ali moghadas jafari4, mohammad fayaz5, mostafa hosseini5* 1. sina trauma and surgery research center, sina hospital, tehran university of medical sciences, tehran, iran. 2. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran. 3. department of occupational health engineering, faculty of public health, tehran university of medical sciences, tehran, iran. 4. department of emergency medicine, school of medicine, bushehr university of medical sciences, bushehr, iran. 5. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. *corresponding author: mostafa hosseini; department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, poursina avenue, tehran, iran. tel/fax: +982188989125; email: mhossein110@yahoo.com received: september 2014; accepted: october 2014 abstract introduction: health care providers and health policy managers need updated and valid information regarding causes of death (cod) for development the health care facilities, directing primary prevention, assigning funds, and promoting public health. the major causes of death and its burden have not been yet appropriately identified in iran. although several studies had been carried out in this area, most of them were local or performed in the past years and need to be update. thus, the present study aimed to address the major causes of death and its burden in iran. methods: the present cross-sectional study was performed on graduate students and their families from february to march 2014. through a two-stage random sampling procedure, data on 11315 subjects were obtained. the corresponding age of death, gender, and calendar year of death were inquired. all causes of death were categorized in nine groups including major cardiovascular disease, cancers, motor vehicle accidents, unintentional injuries, intentional injuries, stroke, lower respiratory infections, diabetes, and other reasons. years of life lost (yll) and person years of life lost were computed as the burden of diseases. results: totally, 11315 (50.4% male) subjects were studied. the results regarding death of relatives revealed that 360 deaths occurred (66.9% male). cod in 95 cases (26.4%) was cardiovascular diseases, 64 (17.8%) motor vehicle accidents, 41 (11.4%) cancers, 23 (6.4%) unintentional injuries, 22 (6.1%) intentional injuries, 10 (2.8%) stroke, 8 (2.2%) lower respi ratory infections, 6 (1.8%) diabetes, and 91 (25.3%) other reasons. the average yll due to all cod was 34.4±18.5. yll for motor vehicle accidents and injuries (unintentional and intentional) were higher than cardiovascular diseases (p<0.001). in addition, person years of life lost for motor vehicle accidents were 2613.1 years. cardiovascular diseases (2159.4 years), cancers (1321.0 years), and unintentional injuries (990.4 years) were in the next ranks. conclusion: based on the findings, it seems that cardiovascular diseases, motor vehicle accidents, cancers, intentional and unintentional injuries are the major causes of death in iranian population. most of years of life lost were due to motor vehicle accidents, cardiovascular diseases and cancers, intentional and unintentional injuries, respectively. key words: cause of death; mortality; life expectancy; cardiovascular diseases; traffic accidents cite this article as: saadat s, yousefifard m, asady h, moghadas jafari a, fayaz m, hosseini m. the most important causes of death in iranian population; a retrospective cohort study. emergency. 2015;3(1):16-21. introduction: ealth care providers and health policy managers need updated and valid information regarding causes of death (cod) for development the health care facilities, directing primary prevention, assigning funds, and promoting public health (1). however, due to a high prevalence of deaths and its variation in different geographical regions (2), it is not easy to identify the cod precisely. based on world health organization (who), non-communicable diseases (ncds) will be accountable for 70% of all deaths in 2030. cardiovascular diseases (cvds), cancers, diabetes and chronic lung diseases are the first four causes of death in worldwide (3). the recent who report showed that ischemic h mailto:mhossein110@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 17 emergency (2015); 3 (1): 16-21 heart disease (11.2%), brain stroke (10.6%), lower respiratory tract infections (6.7%), obstructive pulmonary disease (5.8%), diarrhea (4.7%), and hiv/aids (3.01%) are the most important causes of mortality globally. also, this report revealed that bronchus and lung cancer (2.7%), diabetes (2.6%), and traffic accidents (2.2%) have the ranks of seventh to ninth, respectively (4). however, the cod in many countries is different from who reports. for example, trauma and poisoning in iran are in the second rank and traffic accident is in the third (1). there are many reasons for such variations and one of the most important of these diversities is the dissimilarity among risk factors of death in different countries. for instance, in sub-saharan africa malnourishment, domestic air pollutants arising from fuels, and suboptimal breastfeeding are the health problems (5) while, in developed countries obesity, high blood cholesterol, and inappropriate dietary habits are the main health problems (6). therefore, regional and national identification of cod has a high priority. as a result, who has developed some facilities in recent years to evaluate the cod in national, regional, and global scales (7). years of life lost (yll) is used to determine the burden of fetal diseases and the effect of it on quality of life. yll along with years lived with disability (yld) are suggested by who and world bank to display the burden of diseases and health priorities (8). these tools let health policy-makers to determine the priorities to control of diseases and evaluate the effectiveness of preventive programs. the major causes of death and its burden have not been yet appropriately identified in iran. although several studies had been carried out in this area, most of them were local or performed in the past years and need to be update. thus, the present study aimed to address the major causes of death and its burden in iran. methods: study design and setting the present cross-sectional study was performed on graduate students and their families with the goal of finding the main causes of mortality among them from february to march 2014. the target population was all the men and women graduate students of tehran university of medical sciences, tehran, iran and their families. this university as the largest university in the country has accepted students from all the country. thus, determining the cause of mortality among these students and their families is a good representative of cod from whole country. the present study was approved by ethical committee of tehran university of medical sciences. participants all graduate students of tehran university of medical sciences who were studying during 2014 were taken to this study. the lack of consent was considered as the exclusion criteria. two hundred graduate students were enrolled into this study through a two-stage random sampling procedure. in first step, one of the ten faculties was randomly selected and then from the list of students, 200 ones were selected using computer-generated random numbers. in this study, the data on parents, spouse and her/his family, children, brothers and sisters, uncles, aunts and their children were asked from each student. based on our pilot study, it was estimated that by interview with each student, the information of about 50 persons of his/her relatives could be obtained. consequently, by studying 200 students it was expected to provide the information of about 10000 individuals. finally, data on 11315 subjects were obtained. to decrease the potential recall bias, the information of close relatives was only asked. data collection in this study, studied subjects were asked to state any death happened to their relatives. the corresponding age of death, gender, and calendar year of death were inquired. in a pilot study, the validity of questionnaire was verified by expert panel, the reliability of it confirmed through a test-retest from 15 students, and the agreement on answers found to be 93.3%. statistical analysis all causes of death were categorized in nine groups including major cardiovascular disease, cancers, motor vehicle accidents, unintentional injuries, intentional injuries, stroke, lower respiratory infections, diabetes, and other reasons. multinomial logistic regression was used to assess significant differences among the frequency of death in various causes of death. to calculate the yll for each person, age of death was subtracted from his/her life expectancy derived from the life table of iranian population. also, for computing person years of life lost, the number of death was multiplied to average yll for each cod. one-way analysis of variance was performed to compare mean yll and person years of life lost among cods. p<0.05 was considered as significant. results: in the present study by interviewing 200 graduate students, the data on 11315 subjects were collected of whom 5700 (50.4%) were male and 5615 (49.6%) female. the findings on death of relatives revealed that totally 360 deaths occurred because of various reasons, that 241 (66.9%) were male and 119 (33.1%) female. 110 specific causes of death were classified into nine groups as shown in table 1. cod in 95 cases (26.4%) was cardiovascular diseases, 64 (17.8%) motor vehicle accidents, 41 (11.4%) cancers, 23 (6.4%) unintentional injuries, 22 (6.1%) intentional injuries, 10 (2.8%) stroke, 8 (2.2%) lower respiratory infections, 6 (1.8%) diabetes, and 91 (25.3%) other reasons. as table 1 and figure 1 show, cardiovascular diseases has the first rank (p<0.001). figure 2 displays the percentage of death in each age group according to cod. motor vehicle accidents are the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com saadat et al 18 major cause of death in ages younger than 45 years. while in older than 45 years, cardiovascular diseases are the main cause of death. multinomial logistic regression showed that in adults (aged 25-74 years), cardiovascular deaths were significantly higher than deaths due to motor vehicle accidents (p<0.001). the average yll and its 95% confidence interval are shown in table 2 for male and female of different cods. the sverage yll due to all cod was 34.4±18.5. the yll had significant difference among various cods (df: 8, 344; f=9.9; p<0.0001). bonferroni post hoc analysis showed that yll for motor vehicle accidents and injuries (unintentional and intentional) were higher than cardiovascular diseases (p<0.001). total person years of life lost were 12394.8 years. person years of life lost for motor vehicle accidents were 2613.1 years. cardiovascular disease (2159.4 years), cancers (1321.0 years), and unintentional injuries (990.4 years) were also in the next ranks. however, intentional injuries (931.7 years), lower respiratory tract infections (312.0 years), stroke (283.3 years), and diabetes (150.2 years) had the least person years of life lost. discussion: the present study showed that cardiovascular disease, motor vehicle accidents, cancers, intentional and unintentional injuries are the major causes of death in iranian population. also, the motor vehicle accidents deaths had the highest person years of life lost followed by cardiovascular disease, cancers, intentional and unintentional injuries, respectively. like other countries, cardiovascular diseases, motor vehicle accidents, cancers, intentional and unintentional injuries, lower respiratory tract infections, and stroke are the most important causes of mortality in iran. based on who reports, cardiovascular diseases were accounted as the major cod and led to 11 million deaths in 2011. in east asia the burden of cardiovascular diseases has the second rank, too (4). similarly, in this study cardiovascular diseases have the first rank of cod and the second highest burden of death by ylls. this issue arises from changing in iranian lifestyle, which leads to increase the risk factors of cardiovascular diseases. smoking, hypertension, alcohol consumption, weight gain, high blood cholesterol, lower consumption of fruits, and sodium rich foods are the most important risk factors of cardiovascular diseases which have a high prevalence in iranian population (9-13). the primary level of prevention is the most critical strategy for controlling these risk factors. additionally, primary care could provide an easy access to new treatment and medical interventions to control some of these risk factors like hypertension and high blood pressure. applying such proceedings could remarkably reduce the deaths arisen from cardiovascular diseases (14); consequently, these policies have decreased the burden of cardiovascular diseases in developing countries. figure 1: the most common causes of death in the studied population 0.0 10.0 20.0 30.0 other diabetes lower respiratory infections stroke intentional injuries unintentional injuries cancers motor vehicle accidents major cardiovascular diseases percent of death men women 0 10 20 30 40 50 60 <15 15-24 25-34 35-44 45-54 55-64 65-74 75-84 >84 p e r c e n t o f d e a th s i n a g e g r o u p age (years) major cardiovascular diseases motor vehicle accidents cancers unintentional injuries intentional injuries stroke lower respiratory infections diabetes figure 2: age-specific causes of death in the studied population this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 19 emergency (2015); 3 (1): 16-21 motor vehicles accidents have the second rank of cod in this study line with frouzanfar et al. they demonstrated that the death rate due to motor vehicle accidents is higher than twice of the global average. since most of the motor vehicle accidents deaths (81.25%) happen under the age of 45, the rank of its burden is the highest (1, 15). the preventive measures are suggested to improve the road safety, quality and safety of vehicles, and establish strict rules for violators. on the other hand, more coordination among different units such as police stations, fire stations, and emergency departments could improve the service delivery to victims. this management leads to reduce the arrival time to the scene and provide critical interventions faster. cancers are the third cause of mortality and the burden of diseases. in the study of frouzanfar et al cancers has the second rank of cod (1). smoking has a key role in developing cancers as the major risk factor. in addition, household air pollution from solid fuels, urban air pollution caused by fossil fuels, exposure to occupational pollutants, drug usage, and inappropriate diet are other risk factors of cancers (16-18). today, such factors have been dramatically increased in urban areas. therefore, preventive policies should be taken to decrease these risks. moreover, cancer-screening programs could help in early diagnosis, which leads to better treatment response. stomach, lung, and breast cancers are the leadings in iran (19). as a result, increasing the free access to diagnostic tools such as mammography is one of the best screening and preventive interventions, economically. in addition, smoking and inappropriate diet are two critical risk factors that their combination exacerbates the disease status. unfortunately, the prevalence of these two risk factors is high in the country. thus, it is suggested to implement educational programs to improve the nutritional status and smoking cessation. table 1: cumulative incidence of death in the studied population cause of death frequency cumulative incidence of death (%) in dead cases (n=360) in samples (n=11315) male female total male female total male female total cardiovascular diseases 65 30 95 18.1 8.3 26.4 0.57 0.27 0.84 motor vehicle accidents 52 12 64 14.4 3.3 17.7 0.46 0.11 0.57 cancers 25 16 41 6.9 4.4 11.4 0.22 0.14 0.36 unintentional injuries 14 9 23 3.9 2.5 6.4 0.12 0.08 0.20 intentional injuries 20 2 22 5.6 0.6 6.1 0.18 0.02 0.19 stroke 8 2 10 2.2 0.6 2.8 0.07 0.02 0.09 lower respiratory infections 5 3 8 1.4 0.8 2.2 0.04 0.03 0.07 diabetes 4 2 6 1.1 0.6 1.7 0.04 0.02 0.05 other 48 43 91 13.3 11.9 25.2 0.42 0.38 0.80 total 241 119 360 66.9 39.8 100 2.13 1.05 3.18 figure 3: genderspecific person years of life lost stratified by cause of death 0 1000 2000 3000 4000 other diabetes stroke lower respiratory infection intentional injuries unintentional injuries cancer major cardiovascular diseases motor vehicle accidents person years of life lost men women this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com saadat et al 20 in the present study lower respiratory infections as the only communicable diseases were the main cods in iran. however, its rate is lower than other diseases. since 1990 the prevalence of communicable diseases like diarrhea, lower respiratory infections, and tetanus has decreased (4). although iran is a low and middle income country, in recent years effective changes has been made in health promotion which cause to shift disease pattern in the society from communicable diseases to non-communicable diseases, similar to developed countries (15). the present study had some limitations one of the most important of which is the lack of calculating the lived years with disability. if evaluation of this factor was possible, calculating the disability-adjusted life year (daly) would be conceivable, which is critical in finding the burden of diseases. another limitation was recall bias; although complete removing of recall bias in observational studies is not possible, in the present study it decreased noticeably by confining the information of close relatives. conclusion: based on the findings, it seems that cardiovascular diseases, motor vehicle accidents, cancers, intentional and unintentional injuries are the major causes of death in iranian population. most of years of life lost were due to motor vehicle accidents, cardiovascular diseases and cancers, intentional and unintentional injuries, respectively. acknowledgments: the authors would like to thank all the graduate students who cooperated in this study. the present study is the result of a research project enacted by the sina trauma and surgery research center, sina hospital, tehran university of medical sciences, tehran, iran (grant no: 20932). the authors also would like to thank mrs. marziyeh mirzahoseini nejad and mr. milad derakhshan for their invaluable helps. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. forouzanfar mh, sepanlou sg, shahraz s, et al. evaluating causes of death and morbidity in iran, global burden of diseases, injuries, and risk factors study 2010. arch iran med. 2014;17(5):304-20. table 2: mean years of life lost (95 % confidence interval) according to gender cause men women total cardiovascular diseases 22.9 (19.3-26.5) 22.4 (17.4-27.4) 22.7 (19.8-25.6) motor vehicle accidents 40.3 (36.8-43.8) 43.1 (34.7-51.5) 40.8 (37.6-44.0) cancers 30.1 (24.8-36.0) 35.5 (29.5-41.5) 32.2 (27.9-36.5) unintentional injuries 34.6 (24.9-44.2) 56.3 (47.0-65.6) 43.1 (35.0-51.2) intentional injuries 42.7 (39.9-45.4) 39.2 (4.3-82.7) 42.4 (38.5-46.2) stroke 31.2 (14.5-47.4) 16.9 (7.2-26.6) 28.3 (15.0-41.2) lower respiratory infection 32.5 (8.3-56.8) 49.8 (33.6-66.1) 39.0 (22.4-55.6) diabetes 19.1 (15.0-23.2) 36.9 (28.5-45.2) 25.0 (16.9-33.1) other 40.6 (34.3-46.9) 39.8 (32.5-47.0) 40.2 (35.5-44.9) total 33.5 (31.3-35.8) 36.3 (35.6-40.0) 34.4 (32.5-36.4) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 21 emergency (2015); 3 (1): 16-21 2. welch hg, sharp sm, gottlieb dj, skinner js, wennberg je. geographic variation in diagnosis frequency and risk of death among medicare beneficiaries. jama. 2011;305(11):1113-8. 3. hunter dj, reddy ks. noncommunicable diseases. n engl j med. 2013;369(14):1336-43. 4. organization wh. the top 10 causes of death: the 10 leading causes of death in the world, 2000 and 2011. retrieved july; 2013. 5. roth ga, murray cj. the global burden of disease study 2010 does not show a rise in the age-standardized mortality rate for cardiovascular disease in sub-saharan africa. prog cardiovasc dis. 2013;56(3):278-80. 6. lim ss, vos t, flaxman ad, et al. a comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. lancet. 2013;380(9859):2224-60. 7. mathers cd, boerma t, fat dm. global and regional causes of death. br med bull. 2009;92(1):7-32. 8. gaunt e, harvala h, mcintyre c, templeton k, simmonds p. disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (daly) model. j clin virol. 2011;52(3):21521. 9. hosseini m, yousefifard m, taslimi s, et al. trend of blood cholesterol level in iran: results of four national surveys during 1991-2008. acta med iran. 2013;51(9):642-51.. 10. hosseini m, taslimi s, yousefifard m, et al. serum cholesterol level nomograms for iranian population; suggestion for national cut-offs. iran j public health. 2013;42(2):164-71. 11. hosseini m, navidi i, hesamifard b, et al. weight, height and body mass index nomograms; early adiposity rebound in a sample of children in tehran, iran. int j prev med. 2013;4(12): 1414-20. 12. heydari g, heidari f, yousefifard m, hosseini m. smoking and diet in healthy adults: a cross-sectional study in tehran, iran, 2010. iran j public health. 2014;43(4):485-91. 13. hosseini-esfahani f, khameneh amn, mirmiran p, ghanbarian a, azizi f. trends in risk factors for cardiovascular disease among iranian adolescents: the tehran lipid and glucose study, 1999–2008. j epidemiol. 2011;21(5):319-28. 14. he j, gu d, wu x, et al. major causes of death among men and women in china. n engl j med. 2005;353(11):1124-34. 15. naghavi m, shahraz s, sepanlou s, et al. health transition in iran toward chronic diseases based on results of global burden of disease 2010. arch iran med. 2014;17(5):321-35. 16. hosseini m, naghan pa, karimi s, et al. environmental risk factors for lung cancer in iran: a case–control study. int j epidemiol. 2009;38(4):989-96. 17. masjedi mr, naghan pa, taslimi s, et al. opium could be considered an independent risk factor for lung cancer: a casecontrol study. respiration. 2012;85(2):112-8. 18. mordukhovich i, reiter pl, backes dm, et al. a review of african american-white differences in risk factors for cancer: prostate cancer. cancer causes control. 2011;22(3):341-57. 19. forouzanfar mh, foreman kj, delossantos am, et al. breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. lancet. 2011;378(9801):1461-84. emergency. 2018; 6 (1): e16 ca s e re p o rt sudden death following oral intake of metal objects (acuphagia): a case report mohammad ali emamhadi1, fares najari1∗, mohammad javad hedayatshode2, shokoufeh sharif2 1. department of forensic medicine, shahid beheshti university of medical sciences, tehran, iran. 2. forensic medicine dissection hall, tehran, iran. received: january 2018; accepted: february 2018; published online: 5 march 2018 abstract: according to the diagnostic and statistical manual of mental disorders (dsm-5), pica is described as eating one or more non-nutritive, non-food substances over a period of at least 1 month that is severe enough to warrant clinical attention. the present case is a 44-year-old man who was brought to emergency department following severe abdominal pain, but died before admission or receiving any treatments. on the autopsy, 64 bolts and metal fittings (3700 grams) were found in the esophagus, stomach, small intestine, and large intestine of the patient. keywords: death, sudden; intestinal perforation; peritonitis; pica; case report © copyright (2018) shahid beheshti university of medical sciences cite this article as: emamhadi m, najari f, hedayatshode m, sharif sh. sudden death following oral intake of metal objects (acuphagia): a case report. emergency. 2018; 6 (1): e16. 1. introduction according to the diagnostic and statistical manual of mental disorders, fifth edition (dsm-5), pica is described as eating non-nutritive, non-food items for at least 1 month (criteria a), which is sufficiently severe to necessitate clinical attention. this eating behavior is inappropriate for the developmental level of the individual (criteria b) and is not part of a culturally supported practice (criteria c). pica in adults and children above 2 years is considered to be developmentally inappropriate. it is often reported in people with mental disabilities, psychological disorders, and drug abusers (1). the used substances vary depending on their availability and the patient’s age. they often include items such as paper, soap, fabric, hair, wool, plaster, talcum powder, paint, rubber, metal, charcoal, ash, and ice (2). presence of a foreign body in the gastrointestinal tract, especially in high volumes, can cause bleeding, obstruction and rupture of intestines, and subsequently lead to peritonitis, shock, and death (3, 4). so far, several types of pica have been identified around the world, some of which are fatal. herein, we ∗corresponding author: fares najari; department of forensic medicine and toxicology, shohadaye tajrish hospital, shahrdari street, tajrish square, tehran, iran. postal code: 1981964771 tel: 00989123195140 email: fares.hospital@yahoo.com present a 44-year-old man with fatal pica, who had swallowed 64 pieces of bolts and metal fittings. 2. case presentation: the patient was a 44-year-old man with a high-school diploma, who was a construction worker. apart from a history of stimulant and hallucinogenic drug use (amphetamine and hash), he had no history of physical or mental disorders in the past 5 years. his relatives were aware of his craving for metal objects, but they claimed that it had not caused any particular problems. he had no history of psychological problems or psychotic behaviors and beliefs. following severe abdominal pain and nausea, the patient was referred to a general practitioner in a local clinic, with no complaints other than abdominal pain and nausea. in the examination, the patient’s vital signs were stable, and his abdomen was soft with scarce guarding in the epigastric region. he received outpatient treatment (intramuscular injection of hyoscine and ranitidine) and was referred to the hospital for further evaluation. after 30 minutes, he was discharged from the hospital with personal consent. three hours after discharge, the patient’s sister called the emergency medical service (ems) due to his increasing pain and deterioration of his general condition (pallor, hiccup, severe nausea without vomiting, and inability to walk). the paramedic’s bedside examination revealed the followthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. emamhadi et al. 2 figure 1: perforation of duodenum and peritonitis caused by metal objects following acuphagia. ing results: blood pressure: 85/p mmhg; respiratory rate: 25/minute; pulse rate: 140/minute; o2 saturation: 85% on room air; temperature: 37 celsius; blood sugar: 105 mg/dl, and level of consciousness: 13/15 based on glasgow coma scale. after inserting an intravenous line and using normal saline serum, the patient was transferred to the hospital while oxygen was delivered through a nasal cannula. before admission to the hospital, ventricular fibrillation and cardiac arrest occurred, which were followed by cardiopulmonary resuscitation by the paramedic. after hospital admission, resuscitation interventions continued in the emergency department; however, they were unsuccessful and the patient died. considering the unknown cause of his death, his body was transferred to tehran forensic medicine center. according to the autopsy, the cadaver was 170 cm in height and 60 kg in weight. he had a poor physical and hygienic condition upon admission and was covered in the hospital bed sheets. in the examination of rigor mortis, livor mortis was observed with a typical color on the back of the cadaver. death had occurred within the past 24 hours. apart from the injected areas in the cadaver’s right elbow, there was no sign of being beaten. similarly, there was no sign of fracture, dislocation, self-injury, tattooing, choking, defense wound, or electrical mark. no specific problem was observed in the rectal and genital examinations. the skull was opened and examined, which showed no signs of fracture; also, the brain and meninges appeared normal. in the examination of cervical elements, no abnormalities were detected in the pharynx, larynx, or airways other than the presence of a metal nut in the middle third. in the chest, there was no sign of pneumothorax, hemothorax, or pleural effusion. the lungs were anthracotic at the cutting site, but lacked any pus. the heart was 250 grams and showed no abnormalities on further examinations. nevertheless, in the abdominal examination, the peritoneum space contained about 1.5 liter of dull green liquid of half-digested food, as well as fibrin and pus. a circular hole (about 1 cm in diameter) was also observed at the anterior surface of duodenum at a 3cm distance from the pylorus with irregular edges and ecchymosis with rigid consistency, which seemed to have occurred within the past 24 hours. the gastrointestinal tract was cut from the esophagus to the anus. approximately, 64 pieces of metal (bolts, coins, and metal fittings), measured at 3685 gram, were detected and removed from the stomach, small intestine, and colon. images were also acquired (figure 1). the stomach wall included deep erosions with a patchy pattern (figure 1). there were fibrin fibers on the surface of the liver. other parts of the gastrointestinal tract, retroperitoneal space, kidneys, and urinary tract were normal. the cause of death was confirmed as peritonitis caused by duodenal perforation. however, blood, urine, liver, gallbladder, and vitreous body samples were sent for toxicological examinations. in addition, samples from the brain, lung, heart, kidney, liver, and part of perforated duodenal area were sent for pathological tests. the toxicological test results of urine and gallbladder samthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e16 ples were positive for amphetamine and methamphetamine. also, hypertrophy of myocytes in cardiac samples, moderate to severe edema in alveolar space in lungs, and moderate hypoxic/anoxic signs in cerebellum and brain cortexes were reported on the microscopic pathology. 3. discussion acuphagia is described as eating sharp metal objects and is recognized as a type of pica (5). pica refers to eating nonnutritive, non-food items in people without any underlying mental disorders. this condition can be sometimes a feature of some psychiatric disorders (e.g., developmental disorders, autism spectrum disorder, and even schizophrenia), as well as psychosis induced by hallucinogenic drugs (6). in our case, the patient had a history of amphetamine abuse, and acuphagia might have occurred due to hallucinations caused by amphetamine. there are limited studies similar to the present case report. one of the first studies was conducted by hambridge silverman in 1973 (7). a 2.5-year-old girl who had a craving for metal objects was diagnosed with pica. the habit of eating metal objects (such as keys, buttons, and aluminum foils) had started 1.5 years before. the patient was treated for lack of appetite, which disappeared after pica treatment. pica appears to result from some metabolic disorders, such as iron, zinc, calcium, and magnesium deficiencies. it may occur at any stage of one’s life, including childhood, adolescence, and adulthood; however, it is more common in childhood. the present case (a 44-year-old man) had no medical history of metabolic defects in childhood or adulthood. in 2007, hallidy and iroegbu presented a 22-year-old nigerian man with complaints of postnocturnal nausea, cough, muscle weakness, and swelling (5). the primary diagnosis was kwashiorkor (inadequate intake of protein and calorie). however, following radiography, metal objects were detected in the patient’s abdomen. the patient was diagnosed with acuphagia (swallowing metal objects), although this condition is rare among adults. researchers have highlighted the importance of spiritual beliefs (juju or magical arts) and factors such as poverty, loneliness, and neglect in the emergence of eating disorders. such behaviors are commonly reported in countries with traditional tribal cultures. although these beliefs are seen in many countries, our case had no tribal or religious affiliations. in 2008, kariholou and jakareddy presented a case of acuphagia and/or hyalophagia (8). a 20-year-old woman consumed 18 glass bangles, which were broken into 53 pieces (2-7 cm) in her stomach and intestines. the pieces were successfully removed through surgery. in treatment of drug-addict patients with pica, the effects of drugs on their interests, behaviors, and symptoms should be considered. drug use can not only trigger and intensify pica, but also lead to fatal conditions, similar to our patient’s. our case had no history of psychiatric diseases, mental disorders, or physical problems. according to his relatives, he tended to eat metal objects, but this craving did not disrupt his social relationships and activities. on the other hand, drug use and its effects resulted in the masking of duodenal ulcer symptoms, which led to the negligence of the patient’s severe condition when referred to the clinic. if he had been referred to the hospital immediately, he would have probably survived. therefore, in management of patients with abdominal pain, physicians should consider their nutritional behaviors and drug use history. it could be concluded that, acuphagia can be very serious in some cases and may cause emergency conditions, such as intestinal obstruction, perforation, peritonitis, bleeding, acute weight loss, poisoning, and even death. 4. appendix 4.1. acknowledgements we would like to express our special thanks to the forensic center of tehran, iran. 4.2. authors’ contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declared no potential conflict of interest with respect to the authorship and/or publication of this article. 4.4. funding none. references 1. bryant-waugh r, markham l, kreipe re, walsh bt. feeding and eating disorders in childhood. international journal of eating disorders. 2010;43(2):98-111. 2. ebrahimi m, malmir j, mahmoudi-gharaee a, foroughian m. a rare case of gastrointestinal tract foreign body; glassy stomach. emergency. 2017;5(1):e44. 3. hoek hw, van elburg aa. [feeding and eating disorders in the dsm-5]. tijdschrift voor psychiatrie. 2014;56(3):18791. 4. alvarez aaa, parra jf, buitrago da, rodriguez f, moreno a. gastric perforation and phlegmon formation by foreign bodyingestion. emergency. 2014;2(3):141-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. emamhadi et al. 4 5. halliday d, iroegbu f. case report ‘acuphagia’-an adult nigerian who ingested 497 sharp metallic objects. editorial advisory board. 2007;4(2):54. 6. beck da, frohberg nr. coprophagia in an elderly man: a case report and review of the literature. the international journal of psychiatry in medicine. 2005;35(4):417-27. 7. hambidge k, silverman a. pica with rapid improvement after dietary zinc supplementation. archives of disease in childhood. 1973;48(7):567. 8. kariholu p, jakareddy r, hemanthkumar m, paramesh k, pavankumar n. pica–a case of acuphagia or hyalophagia? indian journal of surgery. 2008;70(3):144-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references archives of academic emergency medicine. 2019; 7 (1); e13 rev i ew art i c l e obstetric triage scales; a narrative review farzaneh rashidi fakari1, masoumeh simbar2∗, shahrzad zadeh modares3, hamid alavi majd4 1. student research committee, department of midwifery and reproductive health, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. midwifery and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 3. mahdiyeh hospital clinical research development unit, shahid beheshti university of medical sciences and health service, tehran, iran. 4. department of biostatistics, shahid beheshti university of medical sciences, tehran, iran. received: november 2018; accepted: december 2018; published online: 13 january 2019 abstract: introduction: the growing demand for high-quality obstetric care and treatment has led to the advent and development of a field known as obstetric triage. the present review study aimed to examine the development of tools and criteria for obstetric triage services. methods: in this narrative review, two authors searched for related articles using the keywords of “obstetric triage, gynecology triage, perinatal triage, maternity triage, midwifery triage” and “tool, index, scale, questionnaire, system”. with persian and english language limitation, searches were performed in scopus, google scholar, scientific information database, proquest, medline, embase and web of science databases for articles published from 2000 to 2018. results: out of the 289 articles reviewed in this study, 8 articles met the eligibility criteria. out of these 8 articles, 6 were dedicated to introducing a tool designed and only 2 introduced an obstetric triage system. the obstetric triage tools and systems covered included emergency severity index (esi), obstetric triage acuity scale (otas), birmingham symptom specific obstetric triage system (bsots), maternal fetal triage index (mfti), florida hospital obstetric triage acuity tool, self-assessment questionnaire for gynecologic emergencies (saq-ge) and perinatal emergency team response assessment (petra). overall, the validity and reliability of the studied method were investigated and found to be acceptable in only 5 of the reviewed studies. conclusion: the review showed the lack of consensus on how to devise a single standardized tool or system for obstetric triage. the comparison of different obstetric triage tools and systems demonstrated the need for a standardized and widely-approved system with high validity and reliability and standard definitions for obstetric triage to determine the right priority and waiting times of obstetric care services. keywords: obstetric; reliability; triage; maternal; validity cite this article as: rashidi fakari f, simbar m, zadeh modares sh, alavi majd h. obstetric triage scales; a narrative review. arch acad emerg med. 2019; 7(1): e13. 1. introduction i nsistent effort to make further improvements in health care systems is a key requirement for achieving the goal of sustainable development in regard to maternal mortality and morbidity (1). the demand for high-quality obstetric care and treatment has led to the advent and development of a field known as obstetric triage (2). triage is the process of prioritizing patients based on the severity of their condition in order to provide necessary treatments as efficiently as ∗corresponding author: masoumeh simbar; midwifery and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. phone numbers: +982133020695 fax: +982133020695 postal code: 00989115386991 e-mail address: msimbar@yahoo.com possible in the shortest possible time. therefore, triage is the basis of care delivery procedure in emergency departments (3, 4). obstetric triage unit is the place where maternal patients entering the hospital system are initially processed to receive emergency medical and obstetric care (5, 6). obstetric triage is more specialized than general and trauma triage, as it involves assessing labor condition and fetal well-being and preparing tests and interventions for obstetric problems (7). the most important issues of obstetric triage are patient dissatisfaction and prolonged waiting times (8-10). a prolonged waiting time means leaving patients without examination, which may result in delayed delivery of necessary care and treatment, patient dissatisfaction, and increased mortality and morbidity (11, 12). research has shown that reducing the waiting time actually reduces the hospital stay this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rashidi fakari et al. 2 time, lowers the treatment cost, and saves hospital resources (13). despite these benefits, there is no consensus on the basics of obstetric triage and the rules and criteria that should apply to this procedure (14). although the initial assessment of obstetric patients involves typical procedures of checking vital signs, triggers, preventive measures, etc., these procedures are not specifically designed for obstetric triage and emergency conditions (15, 16). in a study by angelini et al. (2014), it is stated that there is no standardized and widely-accepted tool for obstetric triage in the united states (5). hence, there is a need for a collection of credible evidence compiled through systematic examination, combination, and integration of the findings in this field (17). this requires a narrative review of research literature for comprehensive and in-depth examination of the reports regarding the existing obstetric triage tools and systems. given the importance of the issue and the paucity of such reviews, the present review study was conducted to examine the development of tools and criteria for obstetric triage services. 2. methods: 2.1. search strategy in this narrative review, two authors searched for related articles using the keywords of “obstetric triage, gynecology triage, perinatal triage, maternity triage, midwifery triage” and “tool, index, check list, questionnaire, system”. the search strategy was as follows: [obstetric triage or maternity triage or gynecology triage or perinatal triage or maternity triage and tool or index or check list or questionnaire or system]. after completion of the document search, duplicate articles were first removed. then, the title and abstracts were first assessed by two of the authors and unrelated articles were deleted and then some articles underwent final assessment according to inclusion criteria. 2.2. databases accessed by setting time and language limitations, a search for persian and english articles published in the period from 2000 to 2018 was performed in scopus, google scholar, scientific information database, proquest, medline, embase and web of science databases. 2.3. screening and data extraction documents and books related to scales or systems in obstetric triage were included. full-text not being accessible, nonrelevance to the subject, studies not demonstrating a clear research methodology, conference presentations, case reports, letters to editor, language not being english or persian, and year of publication of the article outside the considered time interval (2000-2018) were considered as exclusion criteria. figure 1: flowchart of article selection. 3. results: in this study, a total of 289 articles were reviewed. out of these 289 articles, 18 were found to be eligible for further study. among them, 8 articles were dedicated to introducing tools and assessing their validity and reliability, 6 introduced a designed tool, and only 2 introduced an obstetric triage system (figure 1). 3.1. obstetric triage acuity scale (otas) this scale was originally designed by smithson et al. (2013) and later expanded by gratton et al. (2016). otas is an obstetric triage scale based on the canadian triage acuity scale (ctas), which consists of five levels: critical, emergency, urgent, semi-urgent, and non-urgent (3, 18). the otas system also facilitates the assessment of the distribution of acuity and flow and care delivery based on acuity. in this scale, the acuity is color coded. the items considered in this scale include the onset of labor, rupture of fetal membranes, bleeding, hypertension, and fetal assessment. this tool covers major pain complaints, abdominal trauma, infection symptoms, substance abuse, and psychological problem. in its final form, the tool also covers hemodynamic stability (examination for shock signs, compromise, and abnormal vital signs), respiratory distress, fetal wellbeing, cervical dilation, and vital pregnancy-specific parameters (3, 19, 20). in a study by smithson et al. (2013), they measured the reliability of otas and determined the patient flow based on 110 triage charts filled by 8 triage nurses. this study found a kappa value between 0.61 and 0.77 for the first to fourth otas levels and a kappa value of 0.87 for the fifth level. they also found this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1); e13 that otas reduced waiting time (21). gratton et al. (2016) also conducted a study on the triage nurses of three hospitals (london health sciences centre, stratford general hospital, and chatham general hospital) to determine the reliability of otas. this study reported that otas has significant and comparable inter-rater reliability (irr) in the studied hospitals and also has significant intra-rater reliability (itr) (19). 3.2. swiss emergency triage scale (sets) designed in 1997 based on the canadian acuity and triage scale, this tool consists of four levels: immediate-lifethreatening, potentially life-threatening, stable situation, and non-urgent situation, which require immediate examination, examination within 20 minutes, examination within 2 hours, and non-urgent examination or referral to clinics, respectively (22). in a prospective study conducted by rubin et al. (2017) on 22 midwives and triage nurses in geneva hospitals, they attempted to determine the psychometric properties of an obstetric triage tool. this study was designed in a two-stage format, which consisted of pre-test and post-test stages with a 6-month interval. the evaluation method involved 30 clinical scenarios designed by a team of experts and a 3d computer simulation. in this study, participants determined the triage based on the swiss emergency triage scale (sets). the inter-rater reliability in the first stage (pretest) was found to be 0.748 (95%ci: 0.653-0.858). in the posttest stage, the inter-rater reliability was calculated to 0.812 (95%ci: 0.726-0.889). overall, the results showed that sets has an icc of 0.7 and can be considered a reliable tool for management of maternal and obstetric emergencies (16). 3.3. birmingham symptom specific obstetric triage system (bsots) this system has been designed by a team of researchers and physicians with expertise in obstetrics and gynecology (23). in this system, the clinical indices and related parameters, which have been determined using the manchester system (24), have been organized in four levels for initial examination and triage. this method of triage involves the assessment of the mother’s medical history, vital signs, pains, and fetal heartbeat by a midwife in the presence of a gynecologist. the bsots manual for time requirements of care delivery makes use of four colors, red, orange, yellow, and green, which refer to the necessity of providing care immediately, within 15 minutes, within 1 hour, and within 4 hours, respectively. also, a standardized algorithm has been developed to investigate abdominal pain, gestational bleeding, hypertension, suspected labor, membrane rupture, decreased fetal movement, and postpartum problems. kenyon et al. (2017) performed a study to design and implement an obstetric triage system for unwanted pregnancy. in this study, a structured audit was conducted on 994 sets of maternity notes, and reliability evaluation was performed using a scenariobased method. the results showed that the system has excellent reliability in assessing the women’s clinical priority (23). 3.4. maternal fetal triage index (mfti) maternal fetal triage index is a clinical tool designed by a team from the association of women’s health, obstetric and neonatal nurses (awhonn) for standardizing the triage of pregnant women. this tool is an algorithm consisting of five levels: 1-stat, 2-urgent, 3-prompt, 4-no urgent, and 5scheduled or requesting a service, to which patient will be assigned based on the assessment of their clinical conditions. the stat level patients require immediate intervention to protect the life of mother or fetus. the urgent level patients are the people showing clinical conditions at the second level of urgency, such as severe pain without labor and risky clinical conditions, and may require higher levels of care. the prompt level conditions include the onset of active labor at the gestational age of over 34 weeks or the delay of labor in women undergoing the labor phase. the no-urgent level conditions include the gestational age of 37 weeks, signs of early labor, and common pregnancy complaints. the final level, which is termed scheduled or requesting a service, refers to conditions that can be safely addressed at a later date (25, 26). in a study by ruhl et al. (2015), they measured the content validity of mfti using i-cvi and s-cvi indices. the results of this study showed that mfti is a reliable tool for triage of pregnant women (26). ruhl et al. (2015) also conducted a study on 211 pregnant women to determine the reliability of mfti. in this study, the minimum reliability of mfti was measured as 0.60 (27). 3.5. florida hospital obstetric triage acuity tool the development of florida hospital obstetric triage acuity tool was first started by paisley et al. in 2007. this tool is a five-level scale with pregnancy criteria for estimating the examination time requirement based on acuity. the first level (immediate) covers the conditions that require immediate action such as resuscitation, respiratory distress, chest pain, trauma, bleeding, presenting fetal parts, umbilical cord prolapse, impending delivery, and seizures (28). the second level (urgent) includes the conditions that should be examined within 15 minutes such as active labor phase, vaginal discharge, preterm labor, spotting, fetal well-being, rupture of fetal membranes, high blood pressure, uti symptoms, mental disorders, history of epilepsy and diabetes, and pain scores of more than 7. the third level (semi-urgent) covers the conditions that must be addressed within 30 minutes, such as r/o labor (irregular uterine contractions at gestational age of more than 37 weeks, mean pain score of 4-6), vaginal discharge, preterm labor at gestational age of more than 37 weeks, fetal well-being, fetal mobility, high blood this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rashidi fakari et al. 4 pressure, mental disorders (with suicide intention or history of suicide attempt), and other factors (repeated c-section, recent trauma due to accident or falling, fever, chills, active nausea, mean pain score of 4-6) (28). the fourth level (lessurgent) includes the conditions that necessitate examination within 60 minutes, such as r/o labor (early labor, mild irregular uterine contractions, back pain at the gestational age of more than 37 weeks, mild pain with mean score of 1-3, vaginal discharge (with blood or mucus, with and without infection), mental disorders (non-ob complaints, insomnia, psychosocial problems, not acting out), and other factors (pain, nausea, gestational vomiting, mild pain with mean score of 1-3). the fifth level (procedure/testing) includes the conditions that necessitate examination within 120 minutes, such as fetal well-being through nst, bpp, ultrasound, other factors (elective c-section, labor induction) and other procedures (incision, breech presentation, betamethasone injection) (28). in the study of kathleen et al. (2011), where they created an obstetric triage tool, the results showed that patients were examined within the specified time based on the acuity of their condition (28). 3.6. self-assessment questionnaire for gynecologic emergencies (saq-ge) saq-ge has been developed using qualitative methods through consultation with a team of french experts. this tool consists of 89 items in six categories: qualitative description of pain, intensity of pain, location of pain, time-course of pain, vaginal bleeding, and other signs (29). huchon et al. (2014) conducted a cohort study to evaluate the performance of saq-ge for the triage of potentially life threatening emergencies (plte) among women. out of the 574 eligible patients who completed the saq-ge form, 516 entered the study. the results of this study showed that the triage based on a standardized questionnaire facilitates the early diagnosis of patients with pltes (29). 3.7. perinatal emergency team response assessment (petra) petra is a non-technical skill group assessment tool consisting of seven main categories, namely mental model, communication, situational awareness, leadership, followership, workload management, and positive/effective behaviors and attitudes, which are scored based on 5-point likert scale. to assess the validity of petra, balki et al. (2017) conducted an observational cohort study on 119 people in toronto. the results showed that petra is easy to understand (80% agreed, 20% somewhat agreed) and easy to use (60% agreed, 40% somewhat agreed) (30). 4. discussion the present study was a narrative review of obstetric triage systems and tools. overall, this review showed that the reliability values reported in the five studies on this subject are acceptable. while the structure of otas and mtfi both consists of five levels, bsots and sets have a four-level structure. in the five-level mfti and florida, the recommended examination times are 0 minutes (immediate), 10 minutes, 30 minutes, 60 minutes and 120 minutes. but the examination times in the five-level florida tool are 0 minutes (immediate), 5-15 minutes, 15-45 minutes, 1-2 hours, and 4 hours, and in bsots these times are 0 minutes (immediate), 15 minutes, 60 minutes, and 240 minutes. in the systematic review by angelini et al. (2014) with the aim of assessing obstetric triage in the past fifteen years, the results showed that the best model in obstetric triage is a model with use of a tool specific for obstetric triage, standardization of assessments, identification of challenges, team training, quality improvement, competent staff, assessment of patient flow with acuity distribution, create a fast track unit, development of clinical protocols in accordance with the rules and regulations (5). a standardized obstetric triage tool may provide the means for better examination of the care quality and the triage of pregnant mothers and their fetus (31). any comparison of different obstetric triage tools should take into account the fact that underlying differences may affect the results of triage (32). the basic prerequisites for determination of care delivery priority and waiting time are access to well-outlined and standardized definitions for obstetric triage and the validity and reliability of the tool used for this purpose (26). according to angelini et al. (2014), there is no standardized and widely-approved tool for obstetric triage in the united states (5). therefore, the validity and reliability of determinants of patient priority in maternal and fetal care cases should be further investigated (5). paisley et al. (2011) have shown that in the absence of a well-defined triage system, patients who fall in the second and third levels of obstetric triage will not be examined in due time, and instead, patients in the fourth and fifth levels will receive care earlier. hence, proper implementation of an obstetric triage tool is of immense clinical importance (28). 5. limitations the limitations of this study included the heterogeneity of the methods adopted in the reviewed studies for reporting the variables of interest and the lack of access to all of the related documents published worldwide as well as gray literature. further research on the existing general triages with potential application in obstetrics is recommended. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1); e13 6. conclusion the review showed the lack of consensus on how to devise a single standardized tool or system for obstetric triage. the comparison of different obstetric triage tools and systems demonstrated the need for a standardized and widelyapproved system for determining the proper priority and waiting times of obstetric care services, with high validity and reliability and standard definitions for obstetric triage. 7. appendix 7.1. acknowledgements this article is extracted from farzaneh rashidi fakari’s thesis, who was a phd student of reproductive health in shahid beheshti university of medical sciences at the time of performing the study. the authors would like to convey their full appreciation to financial support of the research council of the university. 7.2. authors’ contributions all authors made a substantial contribution to writing of the paper draft and met the four criteria for authorship recommended by the international committee of medical journal editors. authors’ orcids farzaneh rashidi fakari: 0000-0001-7498-475x masoumeh simbar: 0000-0003-2843-3150 shahrzad zadeh modares: 0000-0002-0584-4240 hamid alavi majd: 0000-0001-7772-2923 7.3. funding support this study was supported by a grant from the research council of shahid beheshti university of medical sciences. grant number: no.15356 and was approved by the ethics committee of the university receiving the code: ir. sbmu. phnm.1396.1005. 7.4. conflict of interest the authors declare that there is no conflict of interest regarding the publication of this paper. references 1. secretariat c. ensure healthy lives and promote wellbeing for all, at all ages (sdg 3). enhancing the contribution of sport to the sustainable development goals. 2017:52-64. 2. awhonn. women’s health perinatal nursing care quality measures specifications 2013. 3. bullard mj, unger b, spence j, grafstein e, group cnw. revisions to the canadian emergency department triage and acuity scale (ctas) adult guidelines. canadian journal of emergency medicine. 2008;10(2):136-42. 4. goransson ke, ehrenberg a, ehnfors m. triage in emergency departments: national survey. journal of clinical nursing. 2005;14(9):1067-74. 5. angelini d, howard e. obstetric triage: a systematic review of the past fifteen years 1998-2013. mcn: the american journal of maternal/child nursing. 2014;39(5):284-97. 6. matteson ka, weitzen sh, lafontaine d, phipps mg. accessing care: use of a specialized women’s emergency care facility for nonemergent problems. journal of women’s health. 2008;17(2):269-77. 7. goodman dm, srofenyoh ek, olufolabi aj, kim sm, owen md. the third delay: understanding waiting time for obstetric referrals at a large regional hospital in ghana. bmc pregnancy and childbirth. 2017;17(1):216. 8. angelini dj. obstetric triage and advanced practice nursing. the journal of perinatal & neonatal nursing. 2000;13(4):1-12. 9. macdonald c, redondo v, baetz l, boyle m. obstetrical triage. the canadian nurse. 1993;89(7):17. 10. zocco j, williams mj, longobucco db, bernstein b. a systems analysis of obstetric triage. the journal of perinatal & neonatal nursing. 2007;21(4):315-22. 11. johnson m, myers s, wineholt j, pollack m, kusmiesz al. patients who leave the emergency department without being seen. journal of emergency nursing. 2009;35(2):105-8. 12. monzon j, friedman sm, clarke c, arenovich t. patients who leave the emergency department without being seen by a physician: a control-matched study. canadian journal of emergency medicine. 2005;7(2):107-13. 13. asefzadeh s. patient flow analysis in a children’s clinic. international journal for quality in health care. 1997;9(2):143-7. 14. whitby s, ieraci s, johnson d, mohsin m. analysis of the process of triage: the use and outcome of the national triage scale. liverpool: liverpool health service. 1997. 15. swanton r, al-rawi s, wee m. a national survey of obstetric early warning systems in the united kingdom. international journal of obstetric anesthesia. 2009;18(3):253-7. 16. veit-rubin n, brossard p, gayet-ageron a, montandon cy, simon j, irion o, et al. validation of an emergency triage scale for obstetrics and gynaecology: a prospective study. bjog: an international journal of obstetrics & gynaecology. 2017;124(12):1867-73. 17. petitti db. meta-analysis, decision analysis, and costeffectiveness analysis: methods for quantitative synthethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rashidi fakari et al. 6 sis in medicine: oup usa; 2000. 18. murray m, bullard m, grafstein e. revisions to the canadian emergency department triage and acuity scale implementation guidelines. canadian journal of emergency medicine. 2004;6(6):421-7. 19. gratton rj, bazaracai n, cameron i, watts n, brayman c, hancock g, et al. acuity assessment in obstetrical triage. journal of obstetrics and gynaecology canada. 2016;38(2):125-33. 20. mhyre jm, d’oria r, hameed ab, lappen jr, holley sl, hunter sk, et al. the maternal early warning criteria: a proposal from the national partnership for maternal safety. journal of obstetric, gynecologic & neonatal nursing. 2014;43(6):771-9. 21. smithson ds, twohey r, rice t, watts n, fernandes cm, gratton rj. implementing an obstetric triage acuity scale: interrater reliability and patient flow analysis. american journal of obstetrics and gynecology. 2013;209(4):287-93. 22. rutschmann ot, kossovsky m, geissbãijhler a, perneger tv, vermeulen b, simon j, et al. interactive triage simulator revealed important variability in both process and outcome of emergency triage. journal of clinical epidemiology. 2006;59(6):615-21. 23. kenyon s, hewison a, dann s-a, easterbrook j, hamilton-giachritsis c, beckmann a, et al. the design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation. bmc pregnancy and childbirth. 2017;17(1):309. 24. mackway-jones k, marsden j, windle j. emergency triage: manchester triage group: john wiley & sons; 2013. 25. polit df, beck ct, owen sv. is the cvi an acceptable indicator of content validity? appraisal and recommendations. research in nursing & health. 2007;30(4):459-67. 26. ruhl c, scheich b, onokpise b, bingham d. content validity testing of the maternal fetal triage index. journal of obstetric, gynecologic, & neonatal nursing. 2015;44(6):701-9. 27. ruhl c, scheich b, onokpise b, bingham d. interrater reliability testing of the maternal fetal triage index. journal of obstetric, gynecologic & neonatal nursing. 2015;44(6):710-6. 28. paisley ks, wallace r, durant pg. the development of an obstetric triage acuity tool. mcn: the american journal of maternal/child nursing. 2011;36(5):290-6. 29. huchon c, dumont a, chantry a, falissard b, fauconnier a. triage using a self-assessment questionnaire to detect potentially life-threatening emergencies in gynecology. world journal of emergency surgery. 2014;9(1):46. 30. balki m, hoppe d, monks d, sharples l, cooke me, tsen l, et al. the petra (perinatal emergency team response assessment) scale: a high-fidelity simulation validation study. journal of obstetrics and gynaecology canada. 2017;39(7):523-33. e12. 31. association of women’s health o, nurses n. guidelines for professional registered nurse staffing for perinatal units. 2010. 32. farrohknia n, castren m, ehrenberg a, lind l, oredsson s, jonsson h, et al. emergency department triage scales and their components: a systematic review of the scientific evidence. scandinavian journal of trauma, resuscitation and emergency medicine. 2011;19(1):42. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: results: discussion limitations conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e57 le t t e r to ed i to r screening of trauma patients in need of knee radiography by triage nurses and using ottawa knee rule; a letter to editor samad shams vahdati1, alireza ala1, zhila samani2, sasan ghazanfar ahari3, mohammad mirza-aghazadeh-attari4,5∗ 1. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. 2. emergency medicine department, tabriz university of medical sciences, tabriz, iran. 3. student research committee, tabriz university of medical sciences, tabriz, iran. 4. aging research institute, tabriz university of medical sciences, tabriz, iran. 5. medical radiation sciences research group, department of radiology, imam reza hospital, tabriz university of medical sciences, tabriz, iran. received: august 2019; accepted: september 2019; published online: 6 october 2019 cite this article as: shams vahdati s, ala a, samani zh, ghazanfar ahari s, mirza-aghazadeh-attari m. screening of trauma patients in need of knee radiography by triage nurses and using ottawa knee rule; a letter to editor. arch acad emerg med. 2019; 7(1): e57. in some clinical guidelines, emergency triage nurses request radiographies according to the clinical decision-making priorities. while some studies have suggested that nurses are not as accurate as doctors in assessing major complications of trauma to the knee, it is thought that they are as capable in detecting minor traumas and inconsequential episodes (1). many studies have shown that the cost of treatment and the waiting period for patients in the emergency department decrease without missing fractures when traumas are initially assessed by a certified nurse. routinely, a clinical criteria termed ottawa knee rule is utilized to determine if a patient is in need of a knee radiography or not (2, 3). according to this guideline, if a patient with suspected knee trauma meets any of the following criteria, he or she should undergo imaging modalities: age above 55 years, tenderness at head of fibula, isolated tenderness of patella, inability to flex the knee more than 90◦, and inability to bear weight (4). investigating the ability of emergency nursing staff in triage of patients in need of knee radiography, the authors of this article selected 238 trauma patients who were admitted to a tertiary referral trauma center from march 2018 to october 2018, using a random number generator. triage nurses evaluated the patients using ottawa knee rule and recorded their triage level. then, all selected cases were assessed by an ∗corresponding author: mohammad mirza-aghazadeh-attari; medical radiation sciences research group, department of radiology, imam reza hospital, tabriz, iran. email: m.aghazadeh75@yahoo.com, tel: 0413-3338397 emergency physician and the level of triage regarding knee trauma was recorded, again. finally, the patient’s knee radiographs were taken, and the findings of nurses and physicians were compared. a five-hour course was conducted to train the theory and practice of ottawa knee rule to triage nurses. they were provided with a pocket flowchart that helped them be alert during triage. the knee radiographs were obtained by a single machine and interpreted by radiology residents (years 2-4). patients with decreased level of consciousness (glasgow coma scale below 13) or multiple trauma, < 8 years old, with unstable vital signs, and not willing to participate in the study, were excluded. the data were analyzed using spss software version 15.00. finally, 18 patients were excluded due to lack of consent for taking part in the study or being discharged against medical advice, and 220 patients with the mean age of 43.94 ± 20.44 (8 – 95) years were triaged (74.5 % male). the most common trauma mechanism was pedestrian accident with 21.8%, followed by motorcycle accident 18.2%. table 1 depicts the results of radiographies obtained from the patients. the results of triage levels by emergency physicians and triage nurses are presented in table 2. the records of the two groups were significantly different regarding tenderness at the fibular head and inability to bear weight (p <0.05). it should be noted that, despite the 100% sensitivity of the rule in identifying the patients in need of knee radiography (both by physicians and emergency nurses), sensitivity of the test was very low (21.4% by physicians and 8.9% by this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. shams vahdati et al. 2 table 1: frequency of different radiographic findings radiographic finding number (%) femoral shaft fracture 52 (23.6) fibula fracture 44 (20.0) tibia fracture 24 (10.9) tibia & fibula fracture 12 (5.5) pelvic fracture 12 (5.5) intertrochanteric fracture 4 (1.8) femoral fracture with pelvic fracture 4 (1.8) femoral fracture with tibia fracture 4 (1.8) patella fracture 4 (1.8) fracture of the leg with humerus fracture 4 (1.8) no fracture 56 (25.5) emergency nurses). this means that a considerable numbers of cases (20% to 23% of cases) underwent diagnostic imaging and limb radiation without indication. in conclusion, it seems that further training is needed before use of ottawa knee rule by emergency triage nurses in routine triage of trauma patients. 1. appendix 1.1. acknowledgements we would like to thank the emergency medicine research team for their support, as the study was funded by this group. this report contains data obtained from a thesis for receving a speciality degree in emergency medicine residency program by dr. zhila samani. 1.2. author’s contribution ssv: study conception, data collection, approval of the final version aa: data collection, data analysis zs: data collection, manuscript preparation, approval of the final version of the manuscript sga: manuscript preparation, data collection, and final approval mmaa: manuscript preparation, data analysis and approval of the final version authors orcids samad shams vahdati: 0000-0002-4831-6691 alireza ala: 0000-0001-8231-2937 zhila samani: 0000-0002-3245-3234 sasan ghazanfar ahari: 0000-0002-9808-4163 mohammad mirza-aghazadeh-attari: 0000-0001-7927-6912 1.3. conflict of interest no potential conflict of interest exists regarding this article. 1.4. funding and support funding was done by the emergency medicine research team and deputy of research of tabriz university of medical sciences. references 1. szucs pa, richman pb, mandell m. triage nurse application of the ottawa knee rule. academic emergency medicine. 2001;8(2):112-6. 2. bachmann lm, haberzeth s, steurer j, ter riet g. the accuracy of the ottawa knee rule to rule out knee fractures. database of abstracts of reviews of effects (dare): quality-assessed reviews [internet]: centre for reviews and dissemination (uk); 2004. 3. beutel bg, trehan sk, shalvoy rm, mello mj. the ottawa knee rule: examining use in an academic emergency department. western journal of emergency medicine. 2012;13(4):366. 4. stiell ig, wells ga, hoag rh, sivilotti ml, cacciotti tf, verbeek pr, et al. implementation of the ottawa knee rule for the use of radiography in acute knee injuries. jama. 1997;278(23):2075-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e57 table 2: comparison of ottawa knee rule and triage levels by emergency nurses and physicians regarding the screening of patients in need of knee radiography variables physicians nurses p ottawa knee variables age ≥55 68 (30.9) 68 (30.9) na isolated patellar tenderness 104 (47.3) 104 (47.3) na tenderness at the fibular head 76 (41.8) 94 (42.8) 0.048 unable to flex knee to 90âř 160 (72.7) 152 (69.1) 0.231 unable to bear weight 208 (94.5) 216 (98.2) 0.036 triage level level one 8 (3.6) 8 (3.6) level two 164 (74.6) 172 (78.2) 0.632 level three 48 (21.8) 40(18.2) screening characteristics true positive 164 164 true negative 12 5 na false positive 44 51 false negative 0 0 sensitivity 100 (97.1 – 00.0) 100 (97.1 – 100) na specificty 21.4 ( 12.0 – 34.7) 8.9 (3.3 – 20.3) 0.030 ppv 78.8 (72.5 – 84.0) 76.2 (69.9 – 81.6) 0.643 npv 100 (69.9 – 100) 100 (46.3–100) na plr 3.7 (2.7 – 4.8) 3.2 (2.5–4.1) 0.043 nlr 0.0 0.0 na total accuracy 80.0 (74.1 – 58.1) 77.5 (71.5 – 82.8) 0.640 data are presented as frequency (%). na: not applicable. ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references archives of academic emergency medicine. 2020; 8(1): e7 or i g i n a l re s e a rc h pediatric thoracic injury rule out criteria (ptirc) in diagnosis of very low risk children for traumatic intrathoracic injuries; a diagnostic accuracy study mahmoud yousefifard1, mostafa hosseini2, mohammad reza parvizi3∗ 1. department of medicine, aja university of medical science tehran, iran. 2. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 3. department of physiology, school of medicine, aja university of medical science tehran, iran. received: november 2019; accepted: december 2019; published online: 8 january 2020 abstract: introduction: the value of thoracic injury rule out criteria (tirc) as a tool for decreasing the number of unnecessary chest radiographs in children has not been evaluated yet. therefore, the present study was designed as a multi-center study to assess the validity of tirc model in detection of very low risk children for traumatic intrathoracic injuries. methods: in this diagnostic accuracy study, clinical data and chest radiographs of 974 children less than 18 years of age (72.0% boys) who had presented to 5 hospitals, in iran in 2018 were assessed. data gathering and interpretation of radiographs were done by two independent researchers in each hospital. in the end, discriminatory power and calibration of the model was assessed with a 95% confidence interval (95% cl). results: in the present study, age was not a predicting factor of abnormal findings in radiographs of children and adolescents (p=0.75); therefore, it was omitted from tirc model and pediatric tirc (ptirc) was designed. area under the curve of ptirc rule was 0.97 (95% ci: 0.96-0.98) for prediction of abnormal chest xray in children and adolescents. the sensitivity and specificity of ptirc was 100% and 90.1%, respectively. the calibration of this decision rule had great concordance with the perfect line with a slope of 0.99 and intercept of 0.001. there was a 90.1% reduction in the number of unnecessary chest radiographs when using ptirc decision rule. conclusion: ptirc decision rule was introduced in the present study. ptirc has excellent performance in identification of traumatic intrathoracic injuries and decreasing the number of unnecessary chest radiographs. keywords: clinical decision rules; reproducibility of results; multiple trauma; sensitivity and specificity cite this article as: yousefifard m, hosseini m, parvizi m r. pediatric thoracic injury rule out criteria (ptirc) in diagnosis of very low risk children for traumatic intrathoracic injuries; a diagnostic accuracy study. arch acad emerg med. 2020; 8(1): e7. 1. introduction according to advanced trauma life support guidelines, a chest x-ray (cxr) is necessary for all patients presenting to health care centers with multiple trauma in order to rule out traumatic intrathoracic injuries (1). however, studies show that chest radiographs are unnecessary in many circumstances and also low diagnostic yield is reported for cxr (2-5). therefore, decision rules were designed to reduce the number of cxrs in patients with multiple trauma (6, 7). nexus chest was the first decision rule designed for iden∗corresponding author: mohammad reza parvizi, department of physiology, school of medicine, aja university of medical science, etemadzadeh avenue, west fatemi street, tehran, iran; e mail: mparvizi@alumnus.tums.ac.ir; phone: 02143822925 tification of clinically important thoracic injuries following chest trauma. in this model, age more than 60 years, rapid deceleration, presence of chest pain, chest wall tenderness, distracting painful injury, altered mental status and intoxication were considered the most important factors in identification of high risk patients for presence of intrathoracic injuries following blunt chest trauma. however, speed of vehicle at the time of accident being a required factor was a limitation of this model as such data are not usually accessible (6). therefore, forouzanfar et al. designed and introduced thoracic injury rule out criteria (tirc). this model, which is based on data gathered from adults, indicates that a patient who is hemodynamically stable without loss of consciousness and is under 60 years old with no wall pain, chest wall tenderness, decrease in pulmonary sound, crepitation, chest skin abrasion, or dyspnea is considered very low risk this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 2 and does not require a chest radiograph (6). although both nexus chest and tirc models have been validated in adults, there is a wide gap in the field of pediatrics. since calculations of tirc decision rule is easier than nexus chest and its variables can be assessed more readily in the clinic, the present study assesses the validity of tirc in decreasing the number of unnecessary chest radiographs in children with multiple trauma for the first time. 2. methods 2.1. study design and setting in the present diagnostic accuracy study, the value of tirc rule in decreasing the number of unnecessary radiographs was assessed in children with multiple traumas presenting to 5 hospitals in 2018. the study protocol was approved by ethics committee of aja university of medical sciences (code: 91000283). throughout the study period, all researchers adhered to the principles of the helsinki declaration and a consent form was signed by patients or their parents. in addition, data gathering was performed by a physician not included in the medical team of the patient. 2.2. participants children under the age of 18 years presenting to emergency department were included using convenience sampling. exclusion criteria were penetrating trauma, lack of consent, lack of a chest radiograph due to decision of the patient’s physician, patients with a chest radiograph before clinical assessment and discharge before completing data gathering. 2.3. data gathering patients were assessed in a prospective manner from admission and related data were gathered in a predesigned form. assessed data included age, sex, mechanism of trauma, level of consciousness, heart rate (hr), systolic blood pressure (sbp), diastolic blood pressure (dbp), respiratory rate (rr), oxygen saturation level (sao2), and presence of dyspnea, distracting pain, chest skin abrasion, chest tenderness, chest deformity, crepitation, decreased pulmonary sound, chest wall pain, and subcutaneous emphysema. selecting these factors was based on the study by forouzanfar et al. (6). assessing blood pressure in children and adolescents was done according to previous studies (8-10). in summary, blood pressure was measured using an appropriate pediatric cuff from right arm based on krotocof sounds. left hand was used if right hand was injured and a mercury sphygmomanometer was used in all health care centers. the chief researcher in each center confirmed the calibration of all sphygmomanometers as health care centers were using different brands. child facial coding system was used for assessing pain as it is challenging to interview and examine children to estimate the severity of their pain, especially in those less than 7 years of age (11). therefore, facial expressions such as open lips, lowered brows, and mouth stretched wide in both directions were used to assess the presence or absence of pain in children under the age of 7. however, in children more than 7 years old, pain was assessed using interviews and examinations as this age group have higher cognitive skills. level of consciousness was assessed using pediatric glasgow coma scale (gcs) in children under 3 years (12), but standard gcs was used for children between the ages of 3 to 17 (13). after clinical assessments, a cxr was obtained from children under study in antero-posterior and lateral views. chest radiographs were interpreted by emergency medicine physicians in each center who were unaware of the clinical data. at the end, 5% of chest radiographs were presented to a radiologist to confirm the accuracy of the interpretations (inter-rater agreement= 98.3%). abnormal findings in the chest were identified using cxr. the presence of pneumothorax, hemothorax, lung contusion, pneumomediastinum, mediastinal widening, subcutaneous emphysema, fractures of ribs, sternum, clavicle and scapula were considered abnormal findings in chest radiographs. 2.4. statistical analysis calculation of sample size was done using the method proposed in hajian-tilaki’s study (14). therefore, a minimum sample size of 202 children was required considering a prevalence of 6.5% for the presence of abnormal findings in chest radiograph of patients with multiple trauma (15), area under the receiving operating characteristics (roc) curve of 93% for tirc in identification of abnormal findings in cxrs (16) and a marginal error of 3% (d=0.03) in estimation of the presence of an abnormality. data were analyzed using stata version 14.0. patients were categorized as two groups of cxr negative and cxr positive based on findings of chest radiographs and association between demographic factors, baseline factors and variables present in tirc were assessed using chi2 or t-test. thereafter, all significant factors in univariate analysis were entered in a stepwise multiple logistic regression in order to identify independent predictors of positive cxr findings. since variables from multivariate regression model were different from those of tirc model designed by forouzanfar et al. (6), some modifications were made to tirc and pediatric tirc (ptirc) was introduced. in the next step, calibration, discriminatory power and overall performance of this decision rule were assessed in order to evaluate the validity of ptirc rule. area under the roc curve, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were calculated in order to assess the discriminatory power. in the present study, general calibration was assessed by drawing calibration plot. the closer the slope and intercept of calithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e7 figure 1: area under the receiver operating characteristics (roc) curve (a) and calibration plot (b) of thoracic injury rule out criteria in prediction of positive chest radiography findings in children with trauma. bration plot for ptirc are to 1 and 0, respectively, the more perfect the model is for predicting the presence or absence of an abnormality in chest radiographs. in the end, overall performance was assessed using brier score in order to assess the predictive accuracy and predictive reliability of the model. 3. results 3.1. patients’ characteristics during the study period, data was gathered from 974 children consisting of 701 (72.0%) boys and 273 (28.0%) girls. these children had an average age of 8.8±4.3 years (1 to 17 years). vehicle-pedestrian accident (38.9%), vehicle accident (28.7%) and motorcycle accidents (13.6%) were the most important mechanisms of injury. 869 (89.0%) children had a consciousness level of 15 based on gcs. table 1 shows vital signs and clinical data of children on admission to emergency department. chest radiograph findings were abnormal in 126 (12.9%) cases. rib fracture (6.5%), lung contusion (6.4%), pneumothorax (4.4%) and hemothorax (4.0%) were the most common abnormal findings in chest radiographs. 3.2. predictors of positive cxr findings most important predictors of positive cxr are shown in table 2. as shown, male gender (or=3.1; p=0.02), decreased sbp (or=1.1; p=0.03), decreased dbp (or=1.1; p=0.008), decreased rr (or=1.3; p=0.002), decreased pulmonary sound (or=64.4; p<0.0001), loss of consciousness (or=2.3; p=0.006), chest tenderness (or=4.3; p=0.001), crepitation (or=170.3; p<0.0001), chest pain (or=145.2; p<0.0001), dyspnea (or=13.5; p<0.001) and chest skin abrasion (or=15.2; p<0.0001) were the most important predictors of positive cxr. 3.3. pediatric thoracic injury rule out criteria tirc rule is designed for adults. as a result, age more than 60 years is included among factors affecting the prediction of positive cxr. in the present study, age was not a predicting factor of abnormal findings in chest radiograph of children and adolescents. therefore, it was omitted from this model and pediatric thoracic injury rule out criteria (ptirc) was designed. 3.4. value of ptirc rule in prediction of positive cxr in children a) discrimination area under the roc curve of ptirc rule in prediction of abnormal cxr in children and adolescents was 0.97 (95% ci: 0.96-0.98) (figure 1a). sensitivity and specificity of ptirc were 100 and 90.1 percent, respectively. positive and negative predictive values of ptirc were 60.0 and 100 percent, respectively (table 3). b) calibration the calibration plot of ptirc rule in prediction of abnormal cxr findings in children and adolescents is depicted in figure 1b. as shown, calibration of ptirc rule has great conformity with the ideal line with a slope of 0.99 and an intercept of 0.001. c) overall performance in assessing overall performance, brier score and scaled reliability of ptirc in prediction of positive cxr findings were 0.05 and 0.004, respectively. nagelkerke’s r2 of this model was 0.69, which shows the good performance of ptirc rule in prediction of abnormal findings in cxr of children and adolescents (figure 1b). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 4 table 1: baseline and clinical characteristics of studied children based on chest x ray (cxr) findings variable cxr findings total p value normal (n=848) abnormal (n=126) (n=974) age (year) 1-3 123 (14.5) 14 (11.1) 137 (14.1) 4-6 182 (21.5) 30 (23.8) 212 (21.8) 0.75 7-12 352 (41.5) 54 (42.9) 406 (41.7) 13-17 191 (22.5) 28 (22.2) 219 (22.5) gender boys 622 (73.4) 79 (62.7) 701 (72.0) 0.01 girls 226 (26.6) 47 (37.3) 273 (28.0) mechanism of injury motorcycle accident 112 (13.3) 20 (15.9) 132 (13.6) car accident 231 (27.3) 47 (37.3) 278 (28.7) pedestrian accident 338 (40.0) 39 (31.0) 377 (38.9) 0.007 fall ≥ 1.5 meter 40 (4.7) 10 (7.9) 50 (5.2) fall < 1.5 meter 77 (9.1) 10 (7.9) 87 (9.0) other 46 (5.0) 0 (0.0) 46 (4.7) gcs 15 790 (93.2) 77 (61.1) 867 (89.0) <0.0001 13-14 11 (1.3) 29 (23.0) 40 (4.1) 9-12 26 (3.1) 11 (8.7) 37 (3.8) 3-8 21 (2.5) 9 (7.1) 30 (3.1) vital signs hr (per min) 97.4±15.8 100.4±14.0 97.8±15.6 0.04 sbp (mmhg) 113.9±12.8 102.6±19.0 112.4±14.3 <0.0001 dbp (mmhg) 74.7±9.0 67.7±13.9 73.8±10.1 <0.0001 rr (per min) 13.7±1.8 16.3±2.6 14.0±2.2 <0.0001 sao2 (%) 97.7±1.2 95.1±3.2 97.3±1.8 <0.0001 data are presented as mean ± standard deviation or frequency (%). dbp: diastolic blood pressure; gcs: glasgow coma scale; hr: hear rate; rr: respiratory rate; sbp: systolic blood pressure; sao2 : saturation of oxygen. table 2: independent predictors of positive chest radiography in pediatric trauma patients variable odds ratio 95% ci p male gender 3.1 1.2-7.8 0.02 decreased sbp 1.1 1.003-1.2 0.03 decreased dbp 1.1 1.02-1.2 0.008 decreased rr 1.3 1.1-1.5 0.002 decreased pulmonary sound 64.4 15.8-262.0 <0.0001 loss of consciousness 2.3 1.3-4.3 0.006 chest tenderness 4.3 1.8-10.1 0.001 crepitation 170.3 25.4-1141.4 <0.0001 chest wall pain 145.2 49.2-428.8 <0.0001 dyspnea 13.5 5.4-33.8 <0.0001 chest skin abrasion 15.2 5.5-42.0 <0.0001 ci: confidence interval; dbp: diastolic blood pressure; rr: respiratory rate; sbp: systolic blood pressure. 3.5. performance of ptirc in decreasing unnecessary cxr the present study showed that chest radiographs were normal in 848 (87.1%) children and they were unnecessary. 764 (90.1%) of these unnecessary chest radiographs were identifiable using ptirc. therefore, there can be a 90.1% reduction in the number of unnecessary chest radiographs using ptirc rule. no false negatives were observed in this decision rule. decision tree of ptirc rule is depicted in figure 2. 4. discussion decreasing the number of unnecessary radiographs in chest traumas is an issue of great interest among researchers and there are many articles about this topic (6, 7, 15, 16). tirc is one of the most important models introduced for predicting the presence of a positive cxr in adults (16, 17). in the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e7 figure 2: pediatric thoracic injury rule out criteria (ptirc) decision tree. cxr: chest x-ray present study, the value of this decision rule was assessed in children with omitting the age as a factor and then ptirc was designed. performance of ptirc in prediction of positive cxr findings in children and adolescents with trauma is in an excellent level and has a sensitivity and specificity of 100 and 90.1 percent, respectively. the present study is the first study assessing the value of clinical factors in predicting the presence of abnormal findings in cxr of children and adolescents in order to reduce the number of unnecessary radiographs. therefore, the comparison of results of the present study with other studies is not feasible. tirc was first designed and introduced by forouzanfar et al. in 2014 (6). another study by safari et al. validated this model in adults (16). they showed that tirc has a sensitivity and specificity of 100 and 67.7 percent, respectively, in patients with more than 14 years of age. results from the present study in children between the ages of 1to 17 years are in accordance with the findings of previous studies. in the fitted multivariable regression model of the present study, all variables present in tirc, except age, had a meaningful association with the presence of positive cxr findings. therefore, ptirc was designed by omitting the age as a variable from the previous model and this omission did not influence the value of the mentioned model in prediction of positive findings in cxr of children. in addition, it seems that ptirc in children has a greater value compared to tirc in adults because the reported areas under the curve of studies by frouzanfar et al. (auc=0.94) and safari et al. (auc=0.93) were lower than area under the curve of the present study (auc=0.97). nexus chest is another model designed in the past few years in order to decrease the number of unnecessary chest radiographs (7). this model is also designed for adults and its value in children is not assessed yet. additionally, there are other variables present in the nexus chest such as speed of the vehicle at the time of accident, the data of which are not accessible in many emergency wards, hence limiting the use of this decision rule in clinics, especially in developing countries. in contrast, variables present in ptirc are readily accessible in clinics and this improves its applicability. 5. limitation convenience sampling is one of the limitations of the present study. continuous sampling could not be done as researchers were not present in emergency departments all day. therefore, some degree of selection bias may be present in the study. interpretation of chest radiographs by different physicians is another limitation of the present study. finally, occult pneumothorax might have been present in some children who were categorized as healthy in the present study. 6. conclusion the present study assessed the value of tirc in decreasing the number of unnecessary chest radiographs in traumatic children for the first time. the present study showed that among factors of tirc rule, age does not have any association with positive findings in cxr of children. therefore, ptirc was introduced after omission of age as a factor. ptirc had an excellent performance in identification of traumatic chest injuries and decreasing the number of unnecessary chest radiographs. 7. declarations 7.1. acknowledgements we would like to thank all colleagues in the emergency departments who helped us within the project. 7.2. author contribution mahmoud yousefifard and mohammad reza parvizi designed the study. mahmoud yousefifard participated in data gathering. mostafa hosseini analysed the data. mahmoud this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 6 yousefifard wrote the draft and others critically revised the paper. authors orcids mahmoud yousefifard: 0000-0002-3780-8244 mostafa hosseini: 0000-0002-1334-246x mohammad reza parvizi: 0000-0002-0007-8233 7.3. funding/support none. 7.4. conflict of interest there is no conflict of interest. references 1. kortbeek jb, al turki sa, ali j, antoine ja, bouillon b, brasel k, et al. advanced trauma life support, the evidence for change. journal of trauma and acute care surgery. 2008;64(6):1638-50. 2. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, ghanbari mjh, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. emergency. 2015;3(4):127. 3. yousefifard m, baikpour m, ghelichkhani p, asady h, darafarin a, esfahani mra, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. emergency. 2016;4(2):55. 4. rahimi-movaghar v, yousefifard m, ghelichkhani p, baikpour m, tafakhori a, asady h, et al. application of ultrasonography and radiography in detection of hemothorax: a systematic review and meta-analysis. emergency-an academic emergency medicine journal. 2016;4(3):116-26. 5. ebrahimi a, yousefifard m, kazemi hm, rasouli hr, asady h, jafari am, et al. diagnostic accuracy of chest ultrasonography versus chest radiography for identification of pneumothorax: a systematic review and metaanalysis. tanaffos. 2014;13(4):29-40. 6. forouzanfar mm, safari s, niazazari m, baratloo a, hashemi b, hatamabadi hr, et al. clinical decision rule to prevent unnecessary chest x-ray in patients with blunt multiple traumas. emergency medicine australasia : ema. 2014;26(6):561-6. 7. rodriguez rm, anglin d, langdorf mi, baumann bm, hendey gw, bradley rn, et al. nexus chest: validation of a decision instrument for selective chest imaging in blunt trauma. jama surgery. 2013;148(10):940-6. 8. hosseini m, ataei n, aghamohammadi a, yousefifard m, taslimi s, ataei f. the relation of body mass index and blood pressure in iranian children and adolescents aged 7-18 years old. iranian journal of public health. 2010;39(4):126. 9. hosseini m, baikpour m, yousefifard m, yaseri m, fayaz m, shirafkan h, et al. blood pressure nomograms by age and weight for iranian children and adolescents. international journal of pediatrics. 2016. 10. hosseini m, baikpour m, yousefifard m, fayaz m, koohpayehzadeh j, ghelichkhani p, et al. blood pressure percentiles by age and body mass index for adults. excli journal. 2015;14:465. 11. gilbert ca, lilley cm, craig kd, mcgrath pj, bennett sm, montgomery cj. postoperative pain expression in preschool children: validation of the child facial coding system. the clinical journal of pain. 1999;15(3):192-200. 12. holmes jf, palchak mj, macfarlane t, kuppermann n. performance of the pediatric glasgow coma scale in children with blunt head trauma. academic emergency medicine. 2005;12(9):814-9. 13. balestreri m, czosnyka m, chatfield d, steiner l, schmidt e, smielewski p, et al. predictive value of glasgow coma scale after brain trauma: change in trend over the past ten years. journal of neurology, neurosurgery & psychiatry. 2004;75(1):161-2. 14. hajian-tilaki k. sample size estimation in diagnostic test studies of biomedical informatics. journal of biomedical informatics. 2014;48:193-204. 15. wisbach gg, sise mj, sack di, swanson sm, sundquist sm, paci gm, et al. what is the role of chest x-ray in the initial assessment of stable trauma patients? the journal of trauma. 2007;62(1):74-8; discussion 8-9. 16. safari s, yousefifard m, baikpour m, rahimi-movaghar v, abiri s, falaki m, et al. validation of thoracic injury rule out criteria as a decision instrument for screening of chest radiography in blunt thoracic trauma. journal of clinical orthopaedics and trauma. 2016;7(2):95-100. 17. asgarzadeh s, feizi b, sarabandi f, asgarzadeh m. thoracic injury rule out criteria in prediction of traumatic intra-thoracic injuries; a validation study. emerg (tehran). 2017;5(1) e27. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 103 emergency (2015); 3 (3): 103-108 original research brief emergency department patient satisfaction scale (bepss); development of a new practical instrument mohammad atari1*, maryam atari2, 3 1. department of psychology, university of tehran, tehran, iran. 2. faculty of management, university of tehran, tehran, iran. 3. quality-improvement office, moheb hospital, tehran, iran. *corresponding author: mohammad atari; department of psychology, faculty of psychology and educational sciences, university of tehran, jalal ale-ahmad bridge, tehran, iran. tel: + 00989126363263; email: atari@ut.ac.ir received: october 2014; accepted: december 2014 abstract introduction: methodologically correct assessment of patient satisfaction (ps) plays a crucial role for quality-improvement purposes. evaluation of iranian literature on emergency department’s ps resulted in an emerging need for developing a new instrument with satisfactory psychometric properties. the present study, aimed to develop and initially validate a scale to measure ps in emergency departments. methods: a sample of 301 patients was selected in 2014 from two hospitals in tehran. a pool of 24 items was prepared for administering. an item analysis was conducted to evaluate the quality of each item. validity and reliability of the scale were evaluated. the data were analyzed using spss. results: item analysis and exploratory factor analysis yielded in a 20-item scale in five domains named emergency department staff, emergency department environment, physician care satisfaction, general patient satisfaction, and patient’s family’s satisfaction. validity and factor structure of the scale were reported satisfactory. reliability coefficients of the domains ranged between 0.75 and 0.88. conclusion: the findings of the present study provided evidence for psychometric properties of a newly developed scale for ps assessment in emergency departments. five underlying components of ps were found in the item pool. in sum, this scale may be used in research and emergency departments to measure ps. key words: satisfaction, patient; healthcare quality; departments, emergency; reliability and validity; psychometrics cite this article as: atari mo, atari ma. brief emergency department patient satisfaction scale (bepss); development of a new practical instrument. emergency. 2015;3(3):103-8 introduction: atient satisfaction (ps) is the measure of quality in healthcare perceived by patients and roots in different complicated factors (1). several factors should be coordinated with each other to make an appropriate condition for developing and improvement of ps with observing patient's rights in all aspects (2). this topic deserves attention because it is broadly a worthy goal and is a potentially important mediator for a range of outcomes. satisfied patients are statistically more compliant with their medical instructions, suggesting that satisfaction may be an important component in promoting health and well-being (3-5). satisfaction may also directly affect the financial viability of an institution by influencing consumer choice in the future. moreover, it is a highly valuable factor for quality-improvement purposes which is gaining momentum in iran as well as other countries (6). these factors have led to a proliferation of studies on ps over the last years (7). although the field of emergency medicine is comparatively new in iran, it has not been neglected in the ps research. however, like the larger ps body of literature, many of the existing emergency department (ed) ps studies have serious methodological flaws, which has led to inconsistent and, at times, contradictory conclusions (7). in iran, many studies have utilized questionnaires in order to measure ps (8-12); however, no specially designed scale for ed was found reporting satisfactory psychometric properties. studies that utilize such scales have the risk of acquiring limited or inconsistent data (7, 13). as a result, the present study aimed to develop and initially validate brief emergency department patient satisfaction scale (bepss). methods: study design and setting considering the body of literature, effective items in ps evaluation were extracted in a valid and reliable manner. all items aimed to measure a specific aspect of ps. the p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com atari et al 104 preliminary battery of items was then checked for content by a panel of experts including two hospital managers, two quality-improvement officers, one physician, and one psychometrics professional. the aforementioned panel of experts confirmed the face validity of each item. it was then modified to fit the current iranian needs and resources. the items were categorized into seven major domains of admission, nursing, physician care, environment, patient’s family, waiting time, and general satisfaction. authors evaluated the content validity of the instrument in the final step of scale development as well as initial steps. reviews were used to evaluate if the instrument covers required aspects of ed patient satisfaction (7, 11). item selection: exploratory factor analysis (efa) was performed in order to identify underlying components of the instrument. a broad item analysis was conducted prior to efa (14). in this step, items’ exclusion criteria were set as: (a) missing more than 15% of data (b) having inappropriate indices of skewness and kurtosis and (c) inappropriate cross-loadings in efa. components were rotated using the varimax procedure and loadings under 0.4 were suppressed. items with double loadings were categorized considering their contents and conceptual frame of work. each item was scored from four (complete satisfaction) to one (complete dissatisfaction) as the response option was provided in a 4-point scale of likert sort. no reverse scoring was required. total ed patient satisfaction score was calculated by summing all the items’ scores. cronbach’s alpha coefficient was calculated to assess the internal consistency of each domain and total scale as a measure of reliability. initial validation: 301responders were consecutively recruited from two hospitals in tehran, summer of 2014. all participants were given final approved questionnaire by the panel as well as demographic questions. questionnaires with more than five missing values were excluded. demographics consisted of respondent (patient/family), post-examination status (released/hospitalized/else), age, sex, time of admission, delay before admission (waiting time), and educational level. demographic questions were developed in line with the existing literature and on an exploratory basis. the verbal consent of all participants was obtained before administering the questionnaires in the emergency department. questions were read aloud by an assistant for the elderly. moreover, all respondents were assured of the confidentiality of their responses. statistical analysis data entry and analyses were performed in a blinded manner by staff members who were not involved in the process of data collection. statistical analysis was performed using statistical package for the social sciences (spss) software (version 21.0; spss inc, chicago, illinois). an efa with principal components technique was performed. kaiser-meyer-olkin (kmo) measure was calculated to evaluate sampling adequacy. bartlett’s test of sphericity was also performed. finally, one-way analysis of variance (anova) and independent t-test were used to evaluate total satisfaction among different groups derived from demographic characteristics. the minimum value of kmo measure for adequacy of data matrix for factorability was considered as 0.6 (15). p<0.05 was defined as significant. results: considering the body of literature in ps evaluation, 32 items were extracted but the final questionnaire approved by the panel consisted of 24 items. 301 full field questionnaires met the inclusion criteria and were entered in the validation analysis. baseline characteristics of the responders are presented in table 1. items’ descriptive information and results of item analysis are presented in table 2. all items’ indices of skewness and kurtosis were within acceptable range. therefore, no items were discarded in this step of analysis. table 1: baseline characteristics of participants demographic characteristic number (%) respondent patient 132 (43.8) family 165 (54.8) missing 4 (1.4) post-examination released 88 (29.3) hospitalized 51 (16.9) else 108 (35.9) missing 54 (17.9) sex male 186 (61.8) female 109 (36.2) missing 6 (2.0) waiting time (minute) under 5 158 (52.5) 5-10 37 (12.3) more than 10 18 (6.0) missing 88 (29.2) educational level high school or lower 112 (37.2) associate degree 38 (12.6) bachelor’s degree 123 (40.9) master’s or higher 19 (6.3) missing 9 (3.0) admission shift morning shift 142 (47.2) evening shift 45 (14.9) night shift 6 (2.0) missing 108 (35.9) age (years) 53.2 ±18.1 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 105 emergency (2015); 3 (3): 103-108 efa was performed on the 24 items with varimax rotation. kmo measure of sampling adequacy was 0.923. since the minimum value of this measure for adequacy of data matrix for factorability is 0.6, the data matrix had the required assumptions for factor analysis. bartlett’s test of sphericity was significant (p<0.001). four items (3, 7, 9, and 19 in the 24-item version) were discarded in this step because of inappropriate cross-loadings. another efa was performed on the remaining 20 items (kmo=0.925) using varimax rotation and fixed number of five domains (appendix 1). these domains were respectively named as emergency department staff (eds), emergency department environment (ede), physician care satisfaction (pcs), general patient satisfaction (gps), and patient’s family’s satisfaction (pfs). after rotation, these domains accounted for 16.1%, 15.1%, 14.5%, 13.6%, and 11.4% of the total variance. thus, 70.7% of the total variance was explained via these five domains. results of efa are presented in table 3. the total alpha coefficient of the 20-item scale was 0.94. reliability coefficients of domains are presented in table 4. oneway anova and t-test detected no significant difference in satisfaction of patients differentiated by gender, education, post-examination status, and responding person (p>0.05). however, those patients who were visited with shorter waiting times were significantly more satisfied (f=10.267; p<0.001) as predicted (table 5). finally, the overall satisfaction score was inversely associated with waiting time (r=-0.295, p<0.01). discussion: following this study, brief emergency department patient satisfaction scale (bepss) was developed to evaluate the ps. this scale involves 20 items that score 1 to 4 and are categorized in 5 domains (eds, ede, pcs, gps, and pfs). eds are confronted with challenging issues which may reduce the ps (16). the satisfaction of ed clients cannot be achieved without research and an organized way of assessment in the field (17). so, this topic has been considered by researchers for many years to find an appropriate worldwide scale, but the search still goes on (18, 19). variety of cultural effective factors in different countries and even different area may be one of the reasons of limitation for using the current questionnaires (20, 21). in this manner, considering the psychometric properties of ps is also the missing point. thus, assessment of ps within emergency departments of iranian hospitals was in need of a reliable and valid instrument (22). translation of foreign tools without reporting characteristics of the test runs two potential risks. firstly, validity and reliability of such instruments is questionable within iranian population. secondly, crosscultural differences may play a central role in perception of healthcare quality from the viewpoint of patients (23). using unrelated instruments such as inpatient/outpatient satisfaction tools also runs the risk of low face and content validity (24). therefore, a specific scale for table 2: the results of item analysis item* number mean (sd)** skewness kurtosis statistic (sd) statistic (sd) q1 298 2.89 (0.36) -3.90 (0.14) 18.79 (0.28) q2 300 2.88 (0.40) -4.24 (0.14) 21.20 (0.28) q3 283 2.77 (0.49) -2.65 (0.15) 9.47 (0.29) q4 297 2.91 (0.32) -4.49 (0.14) 27.03 (0.28) q5 295 2.88 (0.38) -3.77 (0.14) 16.95 (0.28) q6 280 2.84 (0.43) -3.36 (0.15) 14.50 (0.29) q7 293 2.94 (0.29) -6.00 (0.14) 44.48 (0.28) q8 270 2.74 (0.50) -1.92 (0.15) 4.06 (0.30) q9 259 2.49 (0.62) -0.92 (0.15) 0.32 (0.30) q10 289 2.83 (0.46) -3.04 (0.14) 9.93 (0.29) q11 283 2.71 (0.55) -1.90 (0.15) 3.32 (0.29) q12 275 2.68 (0.59) -2.08 (0.15) 5.20 (0.29) q13 274 2.72 (0.56) -2.10 (0.15) 4.63 (0.29) q14 298 2.92 (0.36) -5.51 (0.14) 35.13(0.28) q15 300 2.85 (0.42) -3.16 (0.14) 11.58(0.28) q16 289 2.68 (0.55) -1.75 (0.14) 3.51 (0.29) q17 276 2.92 (0.34) -4.92 (0.15) 29.16(0.29) q18 266 2.91 (0.34) -4.46 (0.15) 25.25 (0.30) q19 253 2.75 (0.58) -2.46 (0.15) 5.74 (0.31) q20 295 2.77 (0.52) -2.62 (0.14) 8.08 (0.28) q21 288 2.50 (0.71) -1.32 (0.14) 1.15 (0.29) q22 295 2.81 (0.45) -2.57 (0.14) 7.61 (0.28) q23 295 2.84 (0.42) -3.34 (0.14) 14.37 (0.28) q24 299 2.80 (0.49) -2.97 (0.14) 10.74 (0.28) *: see appendix 1; **: sd= standard deviation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com atari et al 106 measuring ps in eds seems essential as emergency patients have complicated and specific situations. one of the problems associated with above-mentioned patients is a lack of time (25). therefore, brevity should be considered quite noteworthy. additionally, adopting nonvalidated approaches of measurement is psychometrically problematic (13). this may also lead to inappropriate data and consequently wrong decisions in managerial levels. measures of ps should adhere to basic principles of psychometric measurement (15, 26). a study analyzed 195 studies of ps and concluded that authors demonstrated a poor understanding of the importance of core measurement properties required if a measure is to assess satisfaction with confidence (26). bepss made an effort to incorporate all effective factors of ps into an integrated measure in order to assess ps in emergency departments. brevity is an extraordinary characteristic of the current instrument. this seems even more essential considering the unusual situation of ed patients. it was illustrated that delay (waiting time) in ed is significantly associated with dissatisfaction of patients. two delay-related items (20 and 21) are present in bepss, which are loaded in the general patient satisfaction (gps) domain. periodic assessment of ps, as a critical indicator in healthcare quality, seems centrally important. strategies for quality-improvement purposes are made upon figures derived from the process of assessment. widening the target population on a national level could have strengthened the results of the study; especially its generalizability. since the primary properties of the scale are very good, this tool calls for further validation across the country. conclusion: it seems that bepss, as a newly developed instrument with highly satisfactory psychometric properties, can be used for the assessment of emergency department’s patient satisfaction. acknowledgments: authors would like to thank those patients who took part in this study. they also appreciate the cooperation of ed staff members of moheb hospital in tehran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. table 5: correlation coefficients between domains and delay before admission waiting time eds ede pcs gps pfc waiting time 1 eds -0.319* 1 ede -0.206* 0.662* 1 pcs -0.066 0.666* 0.511* 1 gps -0.205* 0.704* 0.633* 0.710* 1 pfc -0.251* 0.730* 0.760* 0.531* 0.653* 1 * significant at p<0.01 level. emergency department staff (eds), emergency department environment (ede), physician care satisfaction (pcs), general patient satisfaction (gps), and patient’s family satisfaction (pfs). table 3: the results of exploratory factor analysis (rotated component matrix) items domains eds ede pcs gps pfs 5 0.712 8 0.712 4 0.632 0.415 6 0.587 0.516 2 0.556 0.525 1 0.497 0.434 15 0.723 16 0.670 14 0.666 0.529 24 0.618 0.489 11 0.783 10 0.746 12 0.721 13 0.640 0.478 21 0.698 20 0.696 23 0.669 22 0.520 17 0.775 18 0.748 corresponding loadings are bolded, emergency department staff (eds), emergency department environment (ede), physician care satisfaction (pcs), general patient satisfaction (gps), and patient’s family satisfaction (pfs). table 4: reliability coefficients of five domains domain eds ede pcs gps pfs question (n) 6 3 4 5 2 alpha 0.88 0.75 0.87 0.84 0.87 *: n=number, emergency department staff (eds), emergency department environment (ede), physician care satisfaction (pcs), general patient satisfaction (gps), and patient’s family satisfaction (pfs). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 107 emergency (2015); 3 (3): 103-108 references: 1. andaleeb ss. service quality perceptions and patient satisfaction: a study of hospitals in a developing country. soc sci med. 2001;52(9):1359-70. 2. rahmqvist m, bara a-c. patient characteristics and quality dimensions related to patient satisfaction. int j qual health care. 2010;22(6):86-9. 3. kent s. achieving patient compliance: the psychology of the medical practitioner's role. jama. 1983;250(17):2376-7. 4. ley p. satisfaction, compliance and communication. br j clin psychol. 1982;21(4):241-54. 5. rubin h, wu a. patient satisfaction: its importance and how to measure it. in: g g, editor. the business of medicine: a physician's guide. new york, ny: elsevier science publishing co; 1991. p. 397-409. 6. atari m, akbari zardkhaneh s, atari m, naderi-far n. development and validation of the preliminary version of brief inpatient satisfaction scale (biss). int j hospital res. 2014;3(1): 261-6. 7. boudreaux ed, o'hea el. patient satisfaction in the emergency department: a review of the literature and implications for practice. j emerg med. 2004;26(1):13-26. 8. abbasi s, farsi d, bahrani m, et al. emergency medicine specialty may improve patient satisfaction. med j islam repub iran. 2014;28:61-4. 9. omidvari s, shahidzadeh a, montazeri a, azin s, harirchi a, souri h. patient satisfaction survey in the hospitals of tehran university of medical sciences, tehran, iran. payesh. 2008;2:141-52. [persian]. 10. soleimanpour h, gholipouri c, salarilak s, et al. emergency department patient satisfaction survey in imam reza hospital, tabriz, iran. int j emerg med. 2011;4(1):2-9. 11. mortazavi s, kazemi m, shirazi a, aziz-abadi a. the relationships between patient satisfaction and loyalty in the private hospital industry. iran j public health. 2009;38(3):609. 12. hashemi b, baratloo a, rahmati f, et al. emergency department performance indexes before and after establishment of emergency medicine. emergency. 2013;1(1):20-3. 13. devellis, f r. scale development: theory and applications. newbury park, ca: sage publications; 2011. p. 63-9. 14. nunnally jc, bernstein ih. psychometric theory. 3 ed. new york: mcgraw-hill 1994. p. 261-2. 15. sitzia j. how valid and reliable are patient satisfaction data? an analysis of 195 studies. int j qual health care. 1999;11(4):319-28. 16. taylor c, benger j. patient satisfaction in emergency medicine. emerg med j. 2004;21(5):528-32. 17. zohrevandi b, tajik h. a survey of patients' satisfaction in emergency department of rasht poursina hospital. emergency. 2014;2(4):162-5. 18. larsen dl, attkisson cc, hargreaves wa, nguyen td. assessment of client/patient satisfaction: development of a general scale. eval program plann. 1979;2(3):197-207. 19. horne r, hankins m, jenkins r. the satisfaction with information about medicines scale (sims): a new measurement tool for audit and research. qual health care. 2001;10(3):135-40. 20. arabloo j, rezapour a, azar fef, safari h, mobasheri y. measuring patient safety culture in iran using the hospital survey on patient safety culture (hsops): an exploration of survey reliability and validity. int j hospital res. 2012;1(1):15-24. 21. linder-pelz s. social psychological determinants of patient satisfaction: a test of five hypotheses. soc sci med. 1982;16(5):583-9. 22. arab m, rashidian a, pourreza a, et al. developing a persian inpatient satisfaction questionnaire. int j health care qual assur. 2014;27(1):4-14. 23. grimshaw jm, eccles mp, lavis jn, hill sj, squires je. knowledge translation of research findings. implement sci. 2012;7(1):50-7. 24. mohammadinia l, keshtkaran a, hosseini v, sajadnia z, sarafzadeh s. comparison of the patient satisfaction from inpatient and outpatient fissurectomy in motahari clinic and shahid faghihi hospital, shiraz, iran. j health manage informatics. 2013;1(1):1-6. 25. national center for health statistics. special feature on emergency care. 2 ed. new york. ny: national center for health statistics; 2013. p. 1-39. 26. roberts p. testing user satisfaction tools. nurse res. 1999;6(3):67-76. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com atari et al 108 appendix 1: brief emergency department patient satisfaction scale brief emergency department patients’ satisfaction scale (bepss) 1 2 3 4 emergency department staff (eds) 1. nurses care about my treatment 2. nurses inform me about the remaining of the treatment 3. nurses attended to me patiently 4. nurses relieved me of the pain well 5. admission staff guided me appropriately 6. the behavior of the admission staff was suitable emergency department environment (ede) 7. the environment of the emergency room was calm and quiet 8. emergency room was well equipped 9. the environment of the emergency room was hygienic physician care satisfaction (pcs) 10. the physician told me about my treatment course 11. the behavior of the physician was respectful 12. the physician’s explanation about the remaining of treatment was enough 13. the physician spent a sufficient time examining me general patient satisfaction (gps) 14. the waiting time before seeing the doctor was appropriate 15. the waiting time before admission process was appropriate 16. i would recommend this hospital to my acquaintances 17. i am satisfied with the quality of services in the emergency room 18. the emergency room of this hospital is well functioning patient’s family satisfaction (pfs) 19. the family of the patient are respected in this hospital 20. family can spend an appropriate amount of time besides the patient permission to use this measure is not required; however, seek permission if any item is modified for use in research. for each item, the following response scale should be used: 1 = completely disagree, 2 = mildly disagree, 3 = mildly agree, 4 = completely agree. march 22, 2020 total lab-confirmed cases: 20,610 total associated deaths: 1,556 total recovered cases: 7, 635 new cases: 966 modeling covid-19 deaths in iran to forecast the epidemic trend in iran, a set of dynamic models were created. in these models, the effect of climate and community behavior change on the reproductive number is modeled. a baseline scenario is also defined as letting the epidemic grow naturally, with no prevention/control interventions. different levels of intervention are also defined based on the extent of population isolation. outcomes of each scenario on the number of infected cases are computed. modeling results shows that if effective isolation occurs in 10% of the population, 307,000 individuals will be infected with covid-19 in iran by may 20, 2020. for an isolation rate of 25%, started since march 10, 2020, cumulative number of deaths will be 13,450 individuals by may 20, 2020. if preventive efforts can reach a 32% effective isolation rate, a considerable decrease in the number of new cases would be expected during april and may, and the total number of deaths would decrease to 8,630. if the isolation rate increases to 40%, the total number of infected individuals is expected to be 6,030 individuals. it should be acknowledged that this model predicts the number of deaths of all covid-19 cases, including those who will not be confirmed as covid-19, because of non-testing or death prior to covid-19 identification. this serious health issue requires both long-term and short-term planning and arrangements. social distancing, and identification and isolation of suspected and confirmed cases are believed to be the most important and effective control measure, and should be strengthened soon. for further details on the methodology and results of these models, please visit: http://corona.behdasht.gov.ir/files/site1/files/covid_modeling_v14_26.12.98.pd f next report will be r * day one of the epidemic is assumed to be january 21, 2020. eleased on mrach 21, 2020. geographical distribution of confirmed covid-19 cases in iran source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1000 1500 1 9 -f e b 2 0 -f e b 2 1 -f e b 2 2 -f e b 2 3 -f e b 2 4 -f e b 2 5 -f e b 2 6 -f e b 2 7 -f e b 2 8 -f e b 2 9 -f e b 1 -m a r 2 -m a r 3 -m a r 4 -m a r 5 -m a r 6 -m a r 7 -m a r 8 -m a r 9 -m a r 1 0 -m a r 1 1 -m a r 1 2 -m a r 1 3 -m a r 1 4 -m a r 1 5 -m a r 1 6 -m a r 1 7 -m a r 1 8 -m a r 1 9 -m a r 2 0 -m a r 2 1 -m a r n u m b e r confirmed and cured cases confirmed cases cured cases 0 50 100 150 200 n u m b e r associated deaths 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 5 0 5 5 6 0 6 5 7 0 7 5 8 0 8 5 9 0 9 5 1 0 0 1 0 5 1 1 0 1 1 5 1 2 0 n u m b e r day since the start of the epidemic scenario 1 (25% isolation): cumultive deaths 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 5 0 5 5 6 0 6 5 7 0 7 5 8 0 8 5 9 0 9 5 1 0 0 1 0 5 1 1 0 1 1 5 1 2 0 n u m b e r day since the start of the epidemic scenario 2 (32% isolation): cumultive deaths 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 0 10 20 30 40 50 60 70 80 90 100 110 120 n u m b e r day since the start of the epidemic scenario 3 (40% isolation): cumultive deaths http://corona.behdasht.gov.ir/files/site1/files/covid_modeling_v14_26.12.98.pdf http://corona.behdasht.gov.ir/files/site1/files/covid_modeling_v14_26.12.98.pdf emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 72 emergency (2016); 4 (2): 72-77 original research unintentional home injury prevention in preschool children; a study of contributing factors somaye younesian1, soad mahfoozpour2, ensieh ghaffari shad3, hamid kariman4, hamid reza hatamabadi 2, 4* 1. department of emergency medicine, qom university of medical sciences, qom, iran. 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of emergency medicine, alborz university of medical sciences, karaj, iran. 4. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: hamid reza hatamabadi; emergency department, imam hossein hospital, shahid madani avenue, tehran, iran. tel/fax: +982177557069, email: hhatamabadi@yahoo.com received: june 2015; accepted: august 2015 abstract introduction: different factors such as parents’ knowledge and attitudes regarding preventive measures (pm) have a great role in reducing children unintentional home injuries. the present study aims to evaluate the contributing factors of unintentional home injury prevention in preschool victims presented to the emergency department. methods: the subjects consisted of all the mothers of preschool children who were presented to the emergency department of imam hossein and shohadaie-hafte-tir hospitals, with unintentional home injuries, from march 2011 to february 2012. the participants were divided into two groups according to implementation of preventive measures status. the significant confounding factors of pm application was determined by chi-squared test and entered into the backward multivariate logistic regression model. results: 230 mothers with the mean age of 29.4 ± 5.2 years were evaluated. 225 (97.83%) of them were still married, 74 (32.17%) had high school education or higher, 122 (53.04%) were homemakers, and 31 (13.49%) worked outside the home for at least 8 hours daily. high level of knowledge (or = 0.05; 95% ci: 0.002‒0.32; p = 0.002), appropriate attitude (or = 0.12; 95% ci: 0.03‒0.51; p = 0.01), having at least three children (or = 7.2; 95% ci: 1.1‒32.9; p = 0.04), daily absence of mother for at least 8 hours (or = 9.2; 95% ci: 2.2‒35.46; p = 0.002), and a history of home injury during the previous 3 weeks (or = 8.3; 95% ci: 2.1‒41.3; p = 0.001) were independent factors which influenced application of prev entive measures. conclusion: increasing mothers’ knowledge level and improving their attitudes were facilitating factors and mothers’ absence from the house for more than 8 hours a day and having at least 3 children were obstacles to application of preventive measures. in addition, a history of same injury during the previous 3 weeks increased the risk of repeated event. keywords: accidents, home; wounds and injuries; accident prevention; child, preschool cite this article as: younesian s, mahfoozpour s, ghaffari shad e, kariman h, hatamabadi hr. unintentional home injury prevention in preschool children; a study of contributing factors. emergency. 2016; 4(2): 72-77 introduction: nintentional injuries are the most important causes of morbidity and mortality in 1‒5 year-old children, responsible for 750,000 annual mortalities and 400 million severe injuries/year (1-3). a total of 16 million injured children are admitted to emergency units in the united states each year, 30,000 of which suffer permanent defects (4). the frequency of unintentional injury-induced mortality is very high in iran, and has been reported to be 48 cases in 100,000 general population. it makes up 12% of the total annual mortalities and 82.6% of injury deaths in iran. about 30% of these accidents involve preschool children (5). unintentional home injuries of children are on the rise and have become an important social problem (6, 7). 4 million preschool children suffer from such injuries annually, most important causes of which are falls, poisoning, and burns (8). the most important risk factors reported for home injury include living in unsafe homes, low socioeconomic status, and mothers’ low knowledge and inappropriate attitudes (9-14). a study performed in 14 european countries has shown that the most important obstacle for adopting preventive measures is the inability of u this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 73 emergency (2016); 4 (2): 72-77 mothers to take continuous care of their children, followed by poor knowledge about factors involved in injuries (21). several studies have evaluated the role of parents’ preventive measures in decreasing the incidence of home injuries (15-17). using pm can decrease the incidence of home injuries in some cases, but not in others. for example, the results of a review study showed that application of pm, reduces the incidence of poisoning in children to a great degree (18). however, the results of two other studies showed that, these measures have varying effects or no effect on reducing the incidence rate of falls and burns in children (19, 20). many researches have placed great emphasis on motivations and obstacles faced by mothers to adopt pm. however, the exact role of the majority of these factors is still unknown. although valuable efforts have been made to recognize such factors, the results have been different and even contradictory due to cultural, social, regional and even methodological differences (17, 18, 20). based on the abovementioned, the present study aims to evaluate the contributing factors of unintentional home injury prevention in preschool victims presented to the emergency department. methods: study design and setting this prospective cross sectional study was carried out from march 2011 to february 2012 in imam hossein and shohadaie-hafte-tir hospitals, tehran, iran. the subjects consisted of the mothers of all the preschool children, who had sustained unintentional home injuries, and had been admitted to the emergency departments of the studied hospitals. mothers not interested in taking part in the study were excluded. informed consent was obtained before being included in the study. the protocol of the study was approved by ethics committee of shahid beheshti university of medical sciences. data collection and setting: data were collected using a questionnaire, which consisted of the following sections: a: demographic data, socioeconomic status of mothers, history of unintentional injuries during the previous three weeks, and the condition of the current injury (type, cause, and site of injury). b: 7 questions on the knowledge of mothers about home injuries of preschool children (scores ranged from 0 to 7). c: 12 questions on mothers’ attitude (scores ranged from 0 to 12). d: 15 questions on adoption of preventive strategies (a score of 2 was given to “always”, 1 to “sometimes” and 0 to “never”, scores ranged from 0 to 30). the median of scores gained by the study population was used as a classification cut-point, which is a customary technique for classification of groups (21-23). finally, mothers were divided into two groups (poor and good) based on their application of pm status. the questionnaire was designed under the supervision of two emergency medicine specialists and one epidemiologist. it was given to 20 mothers in a pilot study, and its reliability was confirmed using cronbach’s alpha coefficient (α = 0.78). if the participants could not read or write, the questionnaire was completed by the aid of an oral interview. data were collected after each child received standard treatment so that the mother’s anxiety about her child’s health would not affect data collection. data analysis: the population size was determined, based on previous studies (24), where p = 0.6, α = 0.05, and d = 0.07. a population size of at least 188 subjects was calculated but 230 mothers were evaluated, which increased the study power to 96%. stata 11.0 statistical software program was used for data analysis. after descriptive analysis of data, the relationship between studied variables and application of pm was evaluated by chi-squared and fisher’s exact tests. subsequently, the significant factors, determined by chi-squared test, were entered into the backward multivariate logistic regression model. then the odds ratio (or) was determined at a 95% confidence interval (ci). statistical significance was set at p < 0.05. results: demographic: 230 mothers whose children had sustained unintentional home injuries were evaluated. the mean and the standard deviation (sd) of their age was 29.4 ± 5.2 years. the baseline characteristics of the participants are summarized in table 1. the most common home injury was falls with 145 (63.04%) cases and the most common locations of accidents was living rooms, with 85 (36.96%) cases. table 2 summarizes the injury characteristics. mean score gained by mothers regarding application of pm was 20.3 ± 8.5. the status of pm application was poor in 101 (43.91%) cases and good in 129 (56.09%). 57 (24.78%) mothers had poor knowledge and 134 (58.26%) had inappropriate attitudes towards home injury pm. relationships: table 1 presents the relationship of the mother’s characteristic and application of preventive measure status. in addition, the relationship of injury characteristics and application of preventive measure status is summarized in table 2. multivariate logistic regression analysis showed that daily absence of mother ≥ 8 hours (or = 9.2; 95% ci: 2.2‒35.46; p = 0.002), having at least 3 children (or = 7.2; 95% ci: 1.1‒32.9; p = 0.04) and a history of a home injury during the previous 3 weeks (or = 8.3; 95% ci: 2.1‒41.3; p = 0.001) were predictive factors of poor preventive measure application status by mothers. however, high knowledge level (or = 0.05; 95% ci: 0.002‒ 0.32; p = 0.002) and appropriate attitudes (or = 0.12; this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hatamabadi et al 74 95% ci: 0.03‒0.51; p = 0.01) resulted in adoption of proper pm by mothers. discussion: the results of the present study showed that only table 1: relationship of the mothers’ characteristics with application of preventive measures status variable total (%) preventive measures status (%) p poor good age (year) < 25 53 (23.04) 12 (11.88) 41 (31.78) <0.001 25-30 160 (69.57) 74 (73.27) 86 (66.67) > 30 17 (7.39) 15 (14.85) 2 (1.55) marital status married 225 (97.5) 99 (98.02) 126 (97.67) 0.99 divorced or widowed 5 (2.2) 2 (1.98) 3 (2.33) education level less than diploma 156 (67.83) 30 (29.70) 126 (97.67) <0.001 diploma or higher 74 (32.17) 71 (70.30) 3 (2.33) occupation homemaker 122 (53.04) 0 (0.0) 122 (94.57) <0.001 employee 108 (46.96) 101 (100.0) 7 (5.53) income (per month) < 200 us dollars 24 (11.01) 24 (26.09) 0 (0.0) <0.001 200-399 us dollars 133 (61.01) 66 (71.74) 67 (53.17) 400-800 us dollars 47 (21.56) 2 (2.17) 45 (35.71) > 800 us dollars 14 (6.42) 0 (0.0) 14 (11.11) type of housing leased 82 (36.44) 2 (2.02) 80 (63.49) <0.001 personal 143 (63.54) 97 (97.98) 46 (36.51) type of family core 124 (57.39) 95 (93.1) 29 (23.02) <0.001 widespread 98 (42.61) 1 (1.04) 97 (76.98) number of children 1 63 (27.39) 23 (22.77) 40 (31.01) <0.001 2 132 (57.39) 48 (47.52) 84 (65.11) ≤ 3 35 (15.22) 30 (29.70) 5 (3.88) number of children in preschool 1 185 (80.43) 59 (58.42) 126 (97.67) <0.001 ≤ 2 45 (19.57) 42 (41.58) 3 (2.33) presence at home the continued presence 84 (36.52) 2 (1.98) 82 (63.58) <0.001 4 hours of absence 40 (17.39) 0 (0.0) 40 (31.01) 8 hours of absence 75 (32.61) 71 (70.30) 4 (3.10) > 8 hours of absence 31 (13.49) 28 (27.72) 3 (2.33) child injury in the past 3 weeks no 178 (77.39) 52 (51.49) 126 (97.67) <0.001 yes 52 (22.61) 49 (48.51) 3 (2.33) knowledge poor 57 (24.78) 54 (53.47) 3 (2.33) <0.001 good 173 (75.22) 47 (46.53) 126 (97.67) attitude inappropriate 134 (58.26) 8 (7.92) 126 (97.67) <0.001 appropriate 96 (41.74) 93 (94.8) 3(2.33) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 75 emergency (2016); 4 (2): 72-77 56.09% of mothers whose children had sustained home injuries had applied proper pm. mothers’ characteristics including poor knowledge, inappropriate attitudes, absence from the house ≥ 8 hours, having more than 3 children, and history of child home injuries during the previous 3 weeks were independent predictive factors of poor preventive measure application status. the results of 14 european studies showed that the majority of mothers believed that the most important obstacle for adopting pm was lack of constant care. lack of knowledge about factors involved in injuries was the second most common cause in this regard (24). apart from knowledge, mothers’ appropriate attitudes have an important role in adoption of pm. in the present study, only 58.26% of mothers had appropriate attitudes toward adoption of pm. therefore, in addition to mothers’ knowledge, appropriate attitudes also influence implementation of pm. the results of a study by vladutiu et al. showed that parents’ appropriate attitudes have a direct relationship with improvement in preventive behaviors (25). several studies have placed great emphasis on the role of educational status in improving mothers’ attitudes and performance in relation to the adoption of pm against home injuries. for example, eldosoky et al. showed that educated mothers (university or college education) and mothers with high socioeconomic status have better preventive behaviors (26). in addition, tomruk et al. showed that higher education improves mothers’ knowledge and attitudes regarding prevention of home injuries (27). the major limitation of such studies is ignoring the co-linearity of mothers’ knowledge and her educational status. an increase in educational status results in an increase in mothers’ knowledge level. therefore, educational status is a cofactor for knowledge level. in three studies by eldosoky et al., tomruk et al. and thien et al., this weakness is evident because in these studies mothers’ knowledge was not included as a factor in multivariate regression analysis. to confirm this hypothesis, vladutiu et al. demonstrated that when the relationship between preventive behaviors and mothers’ characteristics (such as attitudes and knowledge) are evaluated, age, educational status, income or the condition of the house (rented or owned) have no effect on preventive behaviors (25). the number of children in the family significantly influences mothers’ preventive behaviors. a study by gielen et al. showed that mothers with at least 3 children exhibit poorer preventive behaviors (28). this decrease in the adoption of pm is attributed to the short duration of time allocated by mothers to their children’s care. a mother with three children dedicates less time to education, upbringing, and even care of each child, compared table 2: the relationship of injury characteristics and application of preventive measure status injury characteristics total (%) preventive measures status (%) p poor good type falling down 145 (63.04) 54 (53.47) 91 (70.54) <0.001 sting 11 (4.78) 6 (5.94) 5 (3.88) penetrating trauma 16 (6.96) 9 (8.91) 7 (4.43) burns 11 (4.78) 7 (6.93) 4 (3.10) poisoning 23 (10.0) 21 (20.79) 2 (1.55) assaulted by other child 16 (6.96) 0 (0.0) 16 (12.40) foreign body ingestion 8 (3.48) 4 (3.96) 4 (3.10) place room 85 (36.96) 28 (27.72) 57 (44.19) 0.001 kitchen 65 (28.26) 48 (47.52) 17 (13.18) stairs 48 (20.87) 18 (17.82) 30 (23.26) bathroom 13 (5.65) 3 (2.97) 10 (7.75) yard 12 (5.22) 3 (2.97) 9 (6.98) parking 7 (3.04) 1 (0.99) 6 (4.65) reason lack of care 29 (12.61) 14 (13.86) 15 (11.63) <0.001 accident 75 (32.61) 11 (10.89) 64 (49.61) caregiver < 10 years old 9 (3.91) 3 (2.97) 6 (4.65) playing 38 (16.52) 14 (13.86) 24 (18.60) availability of hazardous materials 13 (5.65) 7 (6.93) 6 (4.65) unsafe home environment 66 (28.70) 52 (51.49) 14 (10.85) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com hatamabadi et al 76 to a mother with one child or two children. finally, it is suggested that programs be prepared in order to improve and increase mothers’ pm. improving mothers’ knowledge and attitudes might be highly effective in modifying parents’ behaviors. after implementation of such measures, a decrease in child home injuries can be expected. informing mothers of the consequences of serious accidents such as falls, burns, drowning, and poisoning might encourage parents to adopt measures that are more effective. this study had a number of limitations. first, it was a cross sectional study, so no inference can be made about causal relationships between variables. second, the results are based on self-reported data; respondents may have over-reported their injury prevention measures due to social desirability bias. conclusion: the results of the present study showed that only 56.09% of mothers whose children had sustained home injuries had applied proper pm. mothers’ characteristics including poor knowledge, inappropriate attitudes, absence from the house ≥ 8 hours, having more than 3 children, and history of child home injuries during the previous 3 weeks were independent predictive factors of poor preventive measure application status. acknowledgment: we thank dr yousefifard for his kind support for the manuscript. this article was based on a postgraduate thesis by dr. younesian, which was successfully completed under the supervision of dr. hatamabadi and dr. mahfoozpour. this project was supported by a research grant from safety promotion and injury prevention research center. conflict of interest: none funding support: this project was supported by a research grant from safety promotion and injury prevention research center. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. lao z, gifford m, dalal k. economic cost of childhood unintentional injuries. int j prev med. 2012;3(5):303-12. 2. schneiderman ju, leslie lk, hurlburt ms, zhang j, horwitz smc. caregiver reports of serious injuries in children who remain at home after a child protective services investigation. matern child health j. 2012;16(2):328-35. 3. zaloshnja e, miller tr, lawrence ba, romano e. the costs of unintentional home injuries. am j prev med. 2005;28(1):88-94. 4. grossman dc. the history of injury control and the epidemiology of child and adolescent injuries. future child. 2000:23-52. 5. akbari me, naghavi m, h s. epidemiology of deaths from injuries in the islamic republic of iran. east mediterr health j. 2006;12(3-4):382-90. 6. hatamabadi hr, mahfoozpour s, alimohammadi h, younesian s. evaluation of factors influencing knowledge and attitudes of mothers with preschool children regarding their adoption of preventive measures for home injuries referred to academic emergency centres, tehran, iran. international journal of injury control and safety promotion. 2014;21(3):252-9. 7. hatamabadi h, mahfoozpour s, forouzanfar m, khazaei a, yousefian s, younesian s. evaluation of parameter related to preventative measures on the child injuries at home. j saf promot inj prevent. 2013;1(3):140-9. 8. sengoelge m, hasselberg m, laflamme l. child home injury mortality in europe: a 16-country analysis. eur j public health. 2011;21(2):166-70. 9. chen e, matthews ka, boyce wt. socioeconomic differences in children's health: how and why do these relationships change with age? psychol bull. 2002;128(2):295-329. 10. hong j, lee b, ha eh, park h. parental socioeconomic status and unintentional injury deaths in early childhood: consideration of injury mechanisms, age at death, and gender. accid anal prev. 2010;42(1):313-9. 11. hooper r, coggan c, adams b. injury prevention attitudes and awareness in new zealand. inj prev. 2003;9(1):42-7. 12. phelan k, khoury j, atherton h, kahn rs. maternal depression, child behavior, and injury. inj prev. 2007;13(6):403-8. 13. scholer sj, hickson gb, ray wa. sociodemographic factors identify us infants at high risk of injury mortality. pediatrics. 1999;103(6):1183-8. 14. thein mm, lee bw, bun py. knowledge, attitude and practices of childhood injuries and their prevention by primary caregivers in singapore. singapore med j. 2005;46(3):122-6. 15. kendrick d, coupland c, mulvaney c, et al. home safety education and provision of safety equipment for injury prevention. cochrane database syst rev. 2007;1(1):197-204. 16. phelan kj, khoury j, xu y, liddy s, hornung r, lanphear bp. a randomized controlled trial of home injury hazard reduction: the home injury study. arch pediatr adolesc med. 2011;165(4):339-43. 17. smithson j, garside r, pearson m. barriers to, and facilitators of, the prevention of unintentional injury in children in the home: a systematic review and synthesis of qualitative research. inj prev. 2011;17(2):119-26. 18. bruce bs, lake jp, eden va, denney jc. children at risk of injury. j pediatr nurs. 2004;19(2):121-7. 19. carman j, friedman e, lamb d, lennon k. evaluating the impact of a child injury prevention project. community practitioner. 2006;79(6):188-92. 20. ma b, xi hj, wang jl, et al. pediatric burns due to hot water from water dispenser: a neglected issue that should be highly concerned. chin med j (engl). 2012;125(11):2053-6. 21. heydari g, yousefifard m, hosseini m, ramezankhani a, masjedi mr. comparison of cigarette smoking, knowledge, attitude and prediction of smoking for the next five years and their association between students, teachers and clergymen. int j prev med. 2013;4(5):557-64. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 77 emergency (2016); 4 (2): 72-77 22. masjedi mr, naghan pa, taslimi s, et al. opium could be considered an independent risk factor for lung cancer: a case-control study. respiration. 2013;85:112-8. 23. nasrollahzadeh d, kamangar f, aghcheli k, et al. opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of iran. br j cancer. 2008;98(11):1857-63. 24. vincenten ja, sector mj, rogmans w, bouter l. parents' perceptions, attitudes and behaviours towards child safety: a study in 14 european countries. int j inj contr saf promot. 2005;12(3):183-9. 25. vladutiu c, nansel t, weaver n, jacobsen h, kreuter m. differential strength of association of child injury prevention attitudes and beliefs on practices: a case for audience segmentation. inj prev. 2006;12(1):35-40. 26. eldosoky r. home-related injuries among children: knowledge, attitudes and practice about first aid among rural mothers. east mediterr health j. 2012;18(10):1021-7. 27. tomruk o, soysal s, gunay t, cimrin ah. first aid: level of knowledge of relatives and bystanders in emergency situations. adv ther. 2007;24(4):691-9. 28. gielen ac, wilson meh, faden rr, wissow l, harvilchuck jd. in-home injury prevention practices for infants and toddlers: the role of parental beliefs, barriers, and housing quality. health educ behav. 1995;22(1):85-95. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 81 emergency (2015); 3 (2): 81-82 casr report battered child syndrome; a case study arastoo pezeshki1, farzad rahmani2, 3*, hanieh ebrahimi bakhtavar3, sanaz fekri3 1. department of neurosurgery, tabriz university of medical science, tabriz, iran. 2. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. 3. department of emergency medicine, tabriz university of medical sciences, tabriz, iran. *corresponding author: farzad rahmani, department of emergency medicine, sina hospital, azadi avenue, tabriz, iran. tel: +984113352078; fax: +00984113352078; email: rahmanif@tbzmed.ac.ir received: october 2014; accepted: december 2014 abstract one of the important and usual missed causes of pediatric traumas is child abuse. this ominous phenomenon, which can be presented physically, psychologically, sexually, and emotionally has grown significantly in recent years. many children are not diagnosed in the early stages of evaluation. battered child syndrome is used to describe the clinical condition of the child serious physical abuse by parents or caregivers. medical staff should always keep the syndrome in their mind for those brought to the emergency department with trauma. in this report, we described a patient complained of dysphagia following a falling from a height and multiple epidural hematomas and final diagnosis of battered child syndrome. key words: hematoma; brain edema; cerebral palsy; child abuse; battered child syndrome cite this article as: pezeshki a, rahmani f, ebrahimi bakhtavar h, fekri s. battered child syndrome; a case study. emergency. 2014;3(2):81-2. introduction: hysical abuse is one of the specific types of trauma among childhood and should be considered for all pediatric patients who referred to the emergency department (ed) with inexcusable conditions (1, 2). the reported incidence of child abuse in ed approximately is 2-10%, however half of these cases are not reported due to fear of jeopardizing their reputation (3). there has been an increasing trend of child abuse in iran and recent statistics have showed about 3-4 % growth rate during previous years (4-6). to emphasize the importance of this entity, we reported a patient presented with a history of congenital cerebral palsy who was fallen and found as a case of child abuse. case report: the patient was a 17-year-old boy who was brought to the ed with complaint of dysphagia from the last day followed by falling from a height of half meter. the subject was a known case of spastic cerebral palsy who was kept in a care center and brought by the care center staff. as was mentioned, the patient could open his eyes spontaneously, make whining sound, and be able to swallow food easily before falling, but after that, he was not able to swallow or produce sound. in primary assessment, his blood pressure was 120/80 mmhg, pulse rate 95/minute, respiratory rate 16/minute, tympanic temperature 37 ◦c, and 96% oxygen saturation in room air. on physical examination, all four limbs were spastic and he was not able to move the extremities. he opened his eyes in response to painful stimuli. signs of head trauma and swelling were seen on the left side of the head. any signs of erythema, ecchymosis, or swelling were not visible on the chest, abdomen, and extremities. there were no obvious deformities in the long bones and auscultation of the lungs was symmetric on both sides. the abdominal examination was not reliable due to the spasm; however, focused abdominal ultrasonography for trauma (fast) was reported normal. brain computed tomography (ct) scan revealed large volume multiple epidural hematomas with mass effects in the left fronto-temporal lobes (figure 1). the patient was transferred to the operating room and the hematoma evacuation performed. according to the mismatch between mechanisms of injury with ct findings, a complete detailed history was taken again. it seems that the patient had been abused due to his restlessness and lack of cooperation and thus we announced it to the authorities discussion: child abuse is referred to a behavior in which the child is exposed to different physical and/or sexual abuses, neglect or emotional misconduct. the clinical condition of the seriously physically child abused by parents or care givers is called “battered child syndrome” (7, 8). physical child abuse can be manifested with different findings (9). p this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com pezeshki et al 82 figure 1: patient’s brain ct scan abusive head trauma can be seen as multiple subdural hematomas, inter-hemispheric hemorrhage, hypoxicischemic brain injury, and brain edema (10-12). many children are not diagnosed in the early stages of evaluation. in this situation, taking a second detailed case history and reviewing positive findings would be helpful. often a mismatch between the clinical findings and the history, provided by the child caregivers, is a main diagnostic finding among the victims of the battered child syndrome (12). medical staff should provide the victims of the syndrome with appropriate care and contact with the relevant organizations for required interventions. in addition, many governmental organizations have to take effective control measures to create a safe environment for these children (13). health staff should always keep child abuse in their mind in dealing with suspected cases of pediatric trauma to respond appropriately in this regard. acknowledgments: we acknowledge all staff of emergency and neurosurgery departments of fatemi hospital, ardabil, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. reid ja. battered-child syndrome. in: fisher bs, lab sp, editors. encyclopedia of victimology and crime prevention. thousand oaks: ca: sage publications 2010. p. 28-30. 2. dvorak s, howe tr. battered child syndrome. in: goldstein s, naglieri j, editors. encyclopedia of child behavior and development. united state: springer us; 2011. p. 212-3. 3. sedlak aj, mettenburg j, basena m, peta i, mcpherson k, greene a. fourth national incidence study of child abuse and neglect (nis-4). washington, dc: us department of health and human services, administration for children and families, 2010 july. report no. 4. mohammadi mr, zarafshan h, khaleghi a. child abuse in iran: a systematic review and meta-analysis. iran j psychiatr. 2014;9(3):118-24. 5. memarzadeh m, hoseinpour m, sanjary n, karimi z. a study on trauma epidemiology in children referred to isfahan alzahra hospital during 2004-7. feyz j. 2011;14(5): 488-93. [persian]. 6. eslami-shahrbabaki a, eslami-shahrbabaki m, kalantari m. association between parental addiction and types of child abuse in high-school students of kerman, iran. addict health. 2013;5(3-4):108. 7. ramsey ja, lawler bj. the battered child syndrome. pepperdine law review. 2013;1(3):3-7. 8. swischuk le, jadhav sp. battered child syndrome/nonaccidental trauma. emergency musculoskeletal imaging in children. united state: springer; 2014. p. 217-29. 9. crosson-tower c. extrafamilial sexual abuse, misuse, and exploitation. understanding child abuse and neglect. boston, ma: allyn & bacon; 2005. p. 180-211. 10. kemp a, jaspan t, griffiths j, et al. neuroimaging: what neuroradiological features distinguish abusive from nonabusive head trauma? a systematic review. arch dis child. 2011;96(12):1103-12. 11. moharamzadeh p, rahmani f, pouraghaei m, bakhtavar he, abachi em. epidural hematoma following hemodialysis in a methanol poisoned patient; a case report. emergency. 2014;2(1):48-9. 12. dolatabadi aa, baratloo a, rouhipour a, et al. interpretation of computed tomography of the head: emergency physicians versus radiologists. trauma mon. 2013;18(2):86. 13. brinich pm. kempe’s “battered child syndrome” at 50: looking back and forward. psyc critiques. 2013;58(2):1-10. archives of academic emergency medicine. 2019; 7(1): e3 ca s e re p o rt kikuchi-fujimoto disease in an iranian woman; a rare but important cause of lymphadenopathy mana baziboroun1, masomeh bayani1∗, ghodsieh kamrani2, shahab saeedi1, majid sharbatdaran2 1. infectious diseases and tropical medicine research center, health research institute, babol university of medical sciences, babol, iran. 2. department of pathology, school of medicine, babol university of medical sciences, babol, iran. received: september 2018; accepted: october 2018; published online: 1 january 2019 abstract: kikuchi-fujimoto disease (kfd), is a rare and self-limited condition of histiocytic necrotizing lymphadenitis, which typically presents as fever and lymphadenopathy. we describe a case of kfd in an iranian woman. due to low incidence and high importance, awareness of this disease is necessary for clinicians for early diagnosis and appropriate treatment. a 26-year-old woman was admitted to our hospital with a 3-week history of fever and lymphadenopathy. on physical examination, she had three separate enlarged lymph nodes on the right side of her neck. in laboratory tests that were carried out, she had mild anemia and an increase in c-reactive protein (crp) level, erythrocyte sedimentation rate (esr) and lactate dehydrogenase (ldh) level, while other tests were normal. ultasound (u/s) guided core needle lymph node biopsy was performed and based on the histological finding, diagnosis of kikuchi-fujimoto disease was made. the patient was managed supportively and with prednisolone. she symptomatically improved and was discharged with no follow up. although the incidence of kfd is rare, it must be considered as a differential diagnosis of lymphadenopathy especially in tuberculosis-endemic areas like our country-iran. moreover, it is necessary that physicians are aware of this disease in order to minimize unnecessary evaluation and toxic treatment. keywords: histiocytic necrotizing lymphadenitis; fever; lymphadenopathy cite this article as: baziboroun m, bayani m, kamrani gh, saeedi sh, sharbatdaran m. kikuchi-fujimoto disease in an iranian woman; a rare but important cause of lymphadenopathy. arch acad emerg med. 2019; 7(1): e3. 1. introduction kikuchi syndrome, also known as kikuchi-fujimoto disease (kfd) is histologically a histiocytic necrotizing lymphadenitis. the most common presentation of kfd is cervical lymphadenopathy with or without constitutional symptoms in previously healthy individuals. this disease often affects women under the age of 30, and is more common in asia. it is self-limited and resolves spontaneously (1, 2). kfd is an extremely rare disorder. as a result, physicians’ awareness of the disease is minimal (3). the exact cause of the kikuchi disease is still unknown, but viral or autoimmune causes may have a role. however, the role of viruses is controversial (4). kfd is of clinical significance, as it is confused with other illnesses like tuberculosis, lymphoma or systemic lupus erythematosus (sle). no definite laboratory test for kfd has been ∗corresponding author: masomeh bayani; infectious diseases and tropical medicine research center, health research institute, babol university of medical sciences, babol, iran. email: dr.bayani1@yahoo.com. tel: +989113112559 found so far, as a result, diagnosis is to be confirmed through biopsy studies (5). characteristic feature of kikuchi disease in the excisional biopsy of involved lymph nodes is coagulative necrosis with plenty of karyorrhetic debris in paracortical areas (4). in line with the above explanation, an immediate diagnosis and treatment of the disease is important since it prevents unnecessary further tests and patient’s discomfort (6). in the following section, there is a case report of kfd in a young woman here in babol, north of iran. 2. case presentation a 26-year-old woman was admitted to our hospital with a three-week history of fever and painful lymphadenopathy. she initially had observed a painful swelling on the right side of her neck. later, symptoms such as fever, nausea and fatigue were added. despite the application of antibiotics such as amoxicillin/clavulanate and metronidazole, the swelling in the patient’s neck had enlarged gradually. the patient didn’t have any comorbidity. she was a married housewife, living with her family in a village around babol-mazandaran, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. baziboroun et al. 2 figure 1: brain computed tomography scan and magnetic resonance imaging of patient. iran. in addition, she had no recent trip and no significant family history. on the day of admission, she had stable hemodynamics, but further observation showed three separate enlarged lymph nodes on the right side of her neck, without any changes on the skin covering them. the woman was initially treated with clindamycin and naproxen. anyhow, during two weeks of hospital stay, she had a fever ranging from 38-40◦c. laboratory studies demonstrated mild anemia (hemoglobin 10.9 gr/dl, normal range 14-18 gr/dl), with normal white blood cell count (6.4/ml, normal range 4.511/ml). inflammatory markers were increased: c-reactive protein (crp) level peaked at 77mg/l (normal range < 5 mg/l) and erythrocyte sedimentation rate (esr) reached 42 mm/hour (normal range 0-20 mm/hour). the patient’s serum lactate dehydrogenase (ldh) level had also increased to 519 u/l (normal range < 480 u/l). cultures of blood and urine showed no growth and tuberculin skin test was negative. serological tests detected evidence of previous epsteinbarr virus (ebv ) infection, but serologic tests for hiv, hepatitis b and c, toxoplasmosis, venereal disease research laboratory (vdrl), ana and rf were negative. chest radiography and computed tomography (ct) scan of the chest, abdomen and pelvis were unremarkable. ultrasound (u/s) and ct scan of the neck, revealed multiple lymphadenopathy on both sides of the neck, expanding to the base of the neck and intra parotid. on the right side, lymph nodes in the posterior triangle of the neck, had pathologic morphology, with rim enhancement and hypodense center (central necrosis), up to 18 × 14 mm and on the left side, lymph nodes had a reactive view up to 12 × 5 mm (fig. 1). figure 2: brain magnetic resonance angiogram of patient. u/s guided core needle biopsy was performed, which revealed an effaced architecture with extensive coagulation necrosis and nuclear karyorrhexis, especially in the paracortical zone (fig. 2 a). no plasma cell or neutrophil was present. in an immunohistochemistry assessment, we found cd68-positive histiocytes in necrotic areas admixed with numerous cd3-positive t-cells (fig. 2 b&c). b-cells (cd20+) were also seen in remaining lymphoid follicles (fig. 2 d). these findings were compatible with kikuchi’s lymphadenitis. the patient was managed supportively and with prednisolone. after 3 weeks, she symptomatically improved and was discharged with no follow up. 3. discussion kikuchi-fujimoto disease is a rare and benign disease that usually improves spontaneously. in a study performed on 244 cases of kfd, 70% of them were younger than 30 years old and 77% were women. most of the patients come from east asia (50%) (5, 7). while the etiology of kfd remains unknown, infectious, genetic and autoimmune causes have been proposed. various infections such as ebv, herpes viruses, hepatitis b, parvovirus b19, parainfluenza virus, htlv1, human immunodeficiency virus (hiv ), rubella, paramyxovirus, toxoplasmosis, brucellosis, bartonella henselae, and yersiniaenterocolitica have been deemed related to the disease. among them, ebv has been studied more, but its causal relationship has not been proved. other reports have suggested autoimmune origin, especially sle. other autoimmune diseases associated with kfd are as follows: still’s disease, sjogren’s synthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7(1): e3 drome, polymyositis and rheumatoid arthritis. studies have also found that interferon gamma, interleukin-6 and apoptotic cells probably play a role in kfd. others have suggested certain food sources, like raw fish, as a cause (1, 8, 9). the onset of kikuchi disease can be acute or subacute and lasts about 2-3 weeks. fever in 30-50% of cases is a primary symptom, but the main manifestation of the disease in approximately 80% of cases, is unilateral cervical lymphadenopathy, such as in our case (10). although posterior cervical and supraclavicular nodes are involved most commonly, the involvement of other lymph nodes is noted uncommonly, such as axillary, inguinal and mediastinal nodes. generalized lymphadenopathy is even more uncommon. extra nodal extension of kfd has also been rarely reported, affecting skin, myocardium, bone marrow, c.n.s and eye movement. systemic manifestations can also include malaise, headache, night sweats, weight loss and arthralgia (9, 11). no specific laboratory test is available for kikuchi syndrome. anemia, leukopenia, raised esr and crp, and elevated lactate dehydrogenase and immunoglobulin levels can be found in this disease. elevated levels of transaminases and ferritin are rarely found (11, 12). our patient had mild anemia, elevated ldh and raised esr and crp, with normal transaminases. diagnosing the cause of the fever and lymphadenopathy, requires extensive work-up and considering differential diagnoses like lymphoma, tuberculosis, sarcoidosis, toxoplasmosis, cat-scratch disease, mononucleosis, aids and sle; especially in countries where tuberculosis is endemic like iran, kfd can be confused with tuberculosis clinically (1, 3, 13). our patient had negative bacteriological cultures and negative viral serological tests. the result of tuberculin skin test was also negative. clinical and laboratory characteristics in our patient were similar to lymphoma, but unlike lymphoma, enlarged lymph nodes were tender and pathologic results also ruled out lymphoma. the definite diagnosis of kikuchi syndrome is made by excisional biopsy of affected lymph nodes and histological evaluation. fine needle aspiration cytology (fnac) is a cheaper, faster and less invasive method, but the accuracy is only 56%. nevertheless, with clear clinical symptoms and the typical finding of kfd in fnac, the diagnosis of kikuchi disease can be done without lymphadenectomy (12), like what happened in our case. but if clinical finding is unusual, histopathological examination of lymph node by ultrasound-guided biopsy can be an optimal diagnostic method (3). histological examination reveals paracortical foci of coagulation, necrosis and karyorrhetic debris. histiocyte-associated antigens (lysosome, myeloperoxidase and cd68) are also expressed by histiocytes in kfd. however, for pathologists, differentiation of kikuchi disease from other causes of lymphadenopathy such as sle and lymphoma is challenging. the absence of plasmacells or neutrophils are other features in kfd, which rule out the diagnosis of sle. furthermore, absence of reed-sternberg or hodgkin-like cells, is useful in ruling out leukemic process (10, 14). although kikuchi disease is self-limited, has good prognosis, and usually resolves within 1-6 months, it can be recurrent (3-4% of cases) or become complicated with neurological manifestations, hemophagocytic syndromes or heart failure. very rare cases of fatal outcome have also been reported (10). there is no specific treatment for kfd. the best approach is supportive and symptomatic therapy with analgesics and nonsteroidal anti-inflammatory drugs (nsaids). however glucocorticoids can be considered to reduce fever and painful lymphadenopathy, especially in generalized and complicated cases; furthermore, there are case reports of successful treatments with hydroxychloroquine, cyclosporine, azathioprine and intravenous immunoglobulin (1, 11). 4. conclusions this case report highlights the importance of kikuchi disease as differential diagnosis of lymphadenopathy, especially in endemic areas for tuberculosis like our country; because this disease can be easily mistaken for tb, lymphoma and so on. so, although the incidence of kfd is rare, physician’s awareness of this disease is the key to timely diagnosis and minimizing unnecessary evaluations and inappropriate treatment. 5. appendix 5.1. acknowledgements the authors express their appreciation to department of infectious diseases, babol university of medical sciences. 5.2. authors’ contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. authors orcids masomeh bayani: 0000-0003-3044-1168 ghodsieh kamrani: 0000-0001-6553-4693 majid sharbatdaran: 0000-0002-9894-5592 5.3. conflict of interest the authors declare that theres is no conflict of interest. 5.4. funding none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. baziboroun et al. 4 references 1. shahid s, alam sh, hadley i. an unusual presentation of kikuchi-fujimoto disease with recurrent subdural effusion. cureus. 2018;10(3):e2302. 2. lamzaf l, harmouche h, maamar m, adnaoui m, aouni m, tazi mezalek z. kikuchi-fujimoto disease: report of 4 cases and review of the literature. european annals of otorhinolaryngology, head and neck diseases. 2014;131(6):329-32. 3. szczurowska a, pawlowski t, halon a, skoczynska a. a white man with kikuchi-fujimoto disease mimicking lymphoma, preceded by frequent episodes of tonsillitis: a case report. journal of medical case reports. 2017;11(1):39. 4. jamal a-b. kikuchi fujimoto disease. clinical medicine insights arthritis and musculoskeletal disorders. 2012;5:63. 5. kido h, kano o, hamai a, masuda h, fuchinoue y, nemoto m, et al. kikuchi-fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report. bmc neurology. 2017;17:22. 6. zaghloul a, iorgoveanu c, polio a, desai a. kikuchifujimoto disease in a young african american male. cureus. 2018;10(4). 7. mrowka-kata k, kata d, kyrcz-krzemien s, sowa p. kikuchi-fujimoto disease as a rare cause of lymphadenopathy–two cases report and review of current literature. otolaryngologia polska= the polish otolaryngology. 2013;67(1):1. 8. gaman m, vladareanu a-m, dobrea c, onisai m, marinescu c, voican i, et al. a challenging case of kikuchifujimoto disease associated with systemic lupus erythematosus and review of the literature. case reports in hematology. 2018;2018. 9. punjabi rk. necrotizing lymphadenitis: if not tuberculosis then what? journal of family medicine and primary care. 2018;7(1):255. 10. dalugama c, gawarammana ib. fever with lymphadenopathy–kikuchi fujimoto disease, a great masquerader: a case report. journal of medical case reports. 2017;11. 11. srikantharajah m, mahendra p, vydianath b, lowe gc. case report: kikuchi-fujimoto disease: a rare but important differential diagnosis for lymphadenopathy. bmj case reports. 2014;2014. 12. ranabhat s, tiwari m, kshetri j, maharjan s, osti bp. an uncommon presentation of kikuchi fujimoto disease: a case report with literature review. bmc research notes. 2015;8. 13. lame c, loum b, fall a, cucherousset j, ndiaye a. kikuchi-fujimoto disease, a rare cause of lymphadenopathy in africa. description of the first case in senegal and review of the literature. european annals of otorhinolaryngology, head and neck diseases. 2017;134(5):347. 14. pepe f, disma s, teodoro c, pepe p, magro g. kikuchifujimoto disease: a clinicopathologic update. pathologica. 2016;108(3):120. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusions appendix references archives of academic emergency medicine. 2020; 8(1): e18 or i g i n a l re s e a rc h proteomic analysis of patients with epileptic seizure and psychogenic non-epileptic seizure; a cross-sectional study mohsen parvareshi hamrah1, mostafa rezaei tavirani2∗, monireh movahedi1, sanaz ahmadi karvigh3 1. department of biochemistry, faculty of biological science, north tehran branch, islamic azad university, tehran, iran. 2. proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 3. department of neurology, sina hospital, tehran university of medical sciences, tehran, iran. received: february 2020; accepted: february 2020; published online: 11 march 2020 abstract: introduction: there is an increasing interest in the use of different biomarkers to help distinguish psychogenic non-epileptic seizure (pnes) from epileptic seizures (es). this study aimed to evaluate the patterns of differentially expressed serum proteins in es and pnes cases. methods: in this cross-sectional study, 4 patients with mesial temporal lobe epilepsy and 4 patients with pnes were selected from patients with history of recurrent seizures. venous blood samples were obtained within 1 hour after seizure and serum proteomes as well as the extent of protein expression were analyzed. results: 361 proteins were identified; of these, expression of 197 proteins had altered. 110 (55.9%) proteins were down-regulated and 87 (44.1%) were up-regulated in the pnes samples compared to es samples. the mean pi for deregulated proteins with 1.5 to 3 fold changes were 6.69 ± 1.68 in proteins with increasing expression in es group and 5.88 ± 1.39 in proteins with increasing expression in pnes group (p = 0.008). the median and interquartile range (iqr) of molecular weight changes in proteins with 1.5 to 3 fold changes were 64 (22.0-86.0) in proteins whose expression had increased in es group and 39.5 (26.0-61.5) in proteins whose expression had increased in pnes cases (p = 0.05). conclusion: several spots with differential expression were observed by comparing patients with es against the pnes groups, which could be potential biomarkers of the disease. damage to the blood-brain barrier is the most important difference between the two groups, thus identifying total protein changes offers a key to the future of differentiating es and pnes patients. keywords: seizures; proteomics; biomarkers; diagnosis, differential cite this article as: parvareshi hamrah m, rezaei tavirani m, movahedi m, ahmadi karvigh s. proteomic analysis of patients with epileptic seizure and psychogenic non-epileptic seizure; a cross-sectional study. arch acad emerg med. 2020; 8(1): e18. 1. introduction psychogenic non-epileptic seizures (pnes) are neither paroxysmal behavioral changes resembling epileptic seizures (es) without organic cause nor ictal, peri-ictal, and interictal electroencephalography (eeg) changes (1). approximately 80% of patients with video-eeg (veeg) confirmed pnes were taking at least one antiepileptic drug (aed) at the time of diagnosis (2). about 5–20% of patients presenting to an epilepsy unit for veeg monitoring are diagnosed ∗corresponding author: mostafa rezaei tavirani; proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. tel: 00982122439787, e-mail: tavirany@yahoo.com with pnes, and 20–30% of intractable seizures are finally diagnosed as pnes (3). misdiagnosis leads to many years of wrong treatment regimens, experiencing side effects of drugs, additional financial burdens, and adverse effects on social life (4-6). the gold standard for diagnosis is the recording of a typical event with veeg to confirm the absence of electrographic changes on the ictal phase. although veeg monitoring is the gold standard for diagnosis of pnes, it has the limitations of high cost, low accessibility, and long hospitalization. moreover, the habitual events sometimes may not be captured during monitoring. considering the mentioned limitations, other diagnostic tests have been applied to help differentiate es from pnes. comparative proteomic analysis is a powerful diagnostic tool to determine the onset, progression, and prognosis of human diseases. it can identhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. parvareshi hamrah et al. 2 tify a large number of proteins simultaneously, and protein expression alterations corresponding to certain pathological conditions. this integrated way is a useful tool to investigate molecular mechanism of diseases (7). two dimensional polyacrylamide gel electrophoresis (2d-page) enables separation of proteins with different molecular weight and isoelectric point (pi) (8). this method is widely used to perform functional proteomics (i.e., the large-scale analysis of alterations in protein expression levels) (9). using 2d-page to investigate various diseases has indicated that this method provides vital information regarding discovery of biomarkers and understanding the molecular mechanism of disease onset and development (10-12). many studies have shown that 2d-page can determine the differences between normal and es proteomes of cells (13). based on the above-mentioned points, this study aimed to evaluate the patterns of differentially expressed serum proteins in es and pnes cases. 2. methods 2.1. study design and setting in this cross-sectional study, 4 patients with mesial temporal lobe epilepsy and 4 patients with pnes were selected from patients with history of recurrent seizures, who were admitted to epilepsy monitoring unit of sina hospital, tehran, iran, for proteomic analysis. the informed consent form was signed by all the patients before being recruited in the study. this study was approved by ethics committee of shahid beheshti university of medical sciences (code: ir.sbmu.retech.rec.1397.289). 2.2. participants patients with other medical, neurologic or psychiatric diseases (rather than seizure) or history of recent head trauma were excluded from the study. moreover, using medications except anti-epileptic drugs (aeds) or psychoactive drugs was considered an exclusion criterion. 2.3. data gathering age, gender, epilepsy duration and frequency, and the history of medications were recorded for all using a predesigned checklist. all the patients underwent v-eeg to capture enough habitual events. es and pnes cases were differentiated based on v-eeg findings. the epilepsy type was determined by an expert neurologist (epileptologist) based on ictal and inter-ictal eeg findings and the seizures’ semiology. venous blood samples were obtained from all the patients within 1 hour after habitual seizures. serum was separated by centrifugation at 4000 rpm for 10 minutes and aliquots were stored at –80 ◦c. all the proteomics materials were obtained from ge health care life sciences and serva company. we used 2-de clean-up kit (ge healthcare) for proteome extraction from the two groups. following the extraction, determination of protein concentration was done by 2-de quant kit (ge healthcare). the first dimension, isoelectric focusing (14) separates proteins based on their pi. before this step, immobilized ph gradient (ipg) strips were rehydrated for 8 hours. after that, ipg strips were equilibrated for 30 minutes at room temperature in equilibration solution (serva kit). in the next step, separation based on mw was performed by applying hpe flattop tower (horizontal electrophoresis) using 2d hpet m double-gel 12.5% kit (serva company) for about 3.5 hours. after electrophoresis, the gels were stained using serva hpet m coomassie@ staining kit according to the protocol and then scanned using a calibrated gs-800 densitometer (bio-rad) scanner (20). gel analysis was done using progenesis same spots software and 1.5-fold increase or decrease was used as the cut-off value. analysis of image spots (proteins) that appeared on the gel was done based on the following steps: scanning the gel image, identifying protein spots and quantifying (evaluating the color intensity of spot), matching gels, data analysis, data interpretation and finally creation of two-dimensional electrophoresis databases (9). an epileptologist was responsible for data gathering. 2.4. statistical analysis we used x2 test, analysis of variance (anova), and least significant difference (lsd) post hoc test for statistical analysis. the data were analyzed by using spss-16 software. the findings were reported as mean ± standard deviation (sd), median (inter-quartile range; iqr); or frequency (%). the significance level was considered p< 0.05. 3. results 3.1. baseline characteristics of studied cases based on v-eeg findings, 4 patients had mesial temporal lobe epilepsy (es) and 4 patients had pnes. table 1 shows the baseline characteristics of the studied cases. the mean duration of disease was 37.5 ± 7.76 years in es group and 33.25 ± 18.7 years in pnes group. the mean frequency of seizure was in the range of 16.75 ± 15.30 attacks per month in the pnes group, and 3 ± 0.95 episodes per month in the es group. mri findings were normal in pnes group. all es cases and 2 pnes cases were on poly-therapy. only one patient in pnes group and none of those in es group were on psychiatric medications (anti-depressants or neuroleptics). 3.2. proteomic analysis as shown in the figure 1, 361 proteins were identified; of these, expression of 197 proteins had altered. 110 (55.9%) proteins were down-regulated and 87 (44.1%) were upregulated in the pnes samples compared to es samples. distributions of isoelectric point (pi) and molecular weight fold this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e18 table 1: baseline characteristics of patients with epileptic seizure (es) and psychogenic non-epileptic seizure (pnes) variables es* group (n = 4) pnes group (n = 4) gender male 2 (50) 2 (50) female 2 (50) 2 (50) age (years) mean ± sd 37.5 ± 7.76 33.25 ± 18.7 disease duration (years) mean ± sd 7.5 ± 4.20 17.2 ± 9.06 seizure frequency (per month) mean ± sd 3 ± 0.95 16.75 ± 15.30 mri finding left hippocampus sclerosis 2 (50) right hippocampus sclerosis 2 (50) normal na 4 medications aed mono-therapy na 1 (25 ) aed poly-therapy 4 (100 ) 2 (50 ) psychoactive drugs na 1 (25 ) data are presented as mean ± standard deviation (sd) or frequency (%). *: patients with temporal lobe epilepsy. mri: magnetic resonance imaging; aed: antiepileptic drug. changes for deregulated proteins with 1.5 to 3 fold changes in expression are presented in figures 2 and 3. the mean pi for deregulated proteins with 1.5 to 3 fold changes were 6.69 ± 1.68 in proteins with increasing expression in es group and 5.88 ± 1.39 in proteins with increasing expression in pnes group (p = 0.008). the median and interquartile range (iqr) of molecular weight changes in proteins with 1.5 to 3 fold changes were 64 (iqr: 22.0-86.0) in proteins whose expression had increased in es group and 39.5 (iqr: 26.0-61.5) in proteins whose expression had increased in pnes cases (p = 0.05). 4. discussion new diagnostic methods have been found over the past years to help differentiate es from pnes. to date, many biomarkers have been assessed as potential candidates to differentiate es from pnes, such as prolactin (prl) (15, 16), cortisol (17, 18), neuron-specific enolase (nse) (19), brain-derived neurotrophic factor (bdnf) (20), and ghrelin and nesfatin-1 (21) but until now no single biomarker has successfully differentiated pnes from es; in fact, pnes is only diagnosed via the negation of es (22) in this study, different expression of proteins between the two groups allows us to consider the idea of potential protein biomarkers for differential diagnosis of es and pnes. our findings, as depicted in figure 2, showed that up-regulated proteins with higher molecular weights were observed in temporal lobe epilepsy (tle) group relative to the pnes samples. a similar pattern was obtained for pi values and up-regulated proteins in tle had a higher pi value (figure 3). in various neurological disorders, including epilepsy, the bbb (blood brain barrier) is disrupted. disruption of the blood brain barrier also contributes to epileptogenesis by facilitating the exposure of neurons to pro-inflammatory cytokines. it is also thought to play a role in drug resistance by becoming permeable to various transporters and enzymes (16). as a result of increased permeability in the bbb, the molecules that are normally expected to be found only in the central nervous system (cns) may find a chance to diffuse into peripheral blood or on the contrary, serum proteins may reach the brain tissue. some of these molecules are s100 calcium-binding protein β (s100β), neuron-specific enolase, glial fibrillary acidic protein (gfap), and albumin (5). other studies reported that nano bodies with a high pi 9/5 (23, 24) spontaneously cross the bbb. there are two main hypotheses for explaining this observation. first it may be a failure of the bbb. in this regard, small serum proteins with low pi value can penetrate the brain tissue, which leads to decrease in the serum level of these proteins. on the other hand, protein composition of serum is prominently made up of heavy proteins. the second hypothesis is that naturally, the heavy proteins with higher pi value are significantly deregulated in patients. the second hypothesis cannot be true because it is impossible for heavy proteins to be targeted naturally in the patients. as mentioned earlier, bbb damage is reported in es patients. the gross alteration in permeability of bbb after es promotion has been confirmed by several researches. few proteomic studies have been done on epilepsy. some authors have employed proteomic analysis to identify proteins that are differentially expressed in the hippocampus of patients with mesial temporal lobe epilepsy (mtle) compared to control tissue obtained this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. parvareshi hamrah et al. 4 figure 1: position of matched spots on 2de gel by comparing serum samples of epileptic seizure and psychogenic non-epileptic seizure (pnes) cases. the detected proteins were identified using samespots software. via autopsy. the researchers found that several proteins with different roles in the cns were deregulated. the cytosolic enzyme acyl-coa thioester hydrolase, known for its role in energy production via îš-oxidation in mitochondria and peroxisomes, signal transduction, ion fluxes, and activation of protein kinase c, was down-regulated in hippocampus of patients with mtle (25). in subsequent studies, these authors verified a decrease in expression of collapsing responsemediated protein2 (cmrp-2, 55 kda protein), which is often involved in axonal outgrowth, path finding, and neuronal polarity processes (26). they also observed a decrease in expression of 18 proteins playing different roles in brain (25, 27). danis et al. (28) performed a 2d-page study, comparing gaers (genetic absence epilepsy rat from strasbourg) to non-epileptic control (nec) rats. this study showed five differentially expressed proteins, two in the parietal cortex (atp synthase subunit delta and the 14-3-3 zeta isoform), two in the thalamus (myelin basic protein and macrophage migration inhibitory factor (mif)), and the other in the hippocampus (mif and 0-beta 2 globulin). almost all proteins were up-regulated in gaers compared to nec with the exception of 0-beta globulin. in line with this study, mif was also found to be up-regulated in the frontal cortex and in the hippocampus of rats subjected to kainic acid-induced epilepsy (29). mif is a pro-inflammatory cytokine released in response to inflammatory stimuli and is highly expressed in immune and non-immune cells, including those in the brain. a recent study by conboy et al. (30) showed that mif is important to the process of hippocampal neurogenesis, affecting cell proliferation in the dentate gyrus. in a recent study, by using proteomics (2d-page), persike et al. (13) showed that the total number of spots were noticeably smaller in the hippocampus of patients with pharmacoresistant tle than in the control tissue. a total of 16 proteins were differentially this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e18 figure 2: isoelectric point (pi) distribution of proteins with 1.5-3.0 fold change in patients with temporal lobe epilepsy (tle) and psychogenic non-epileptic seizure (pnes) (p = 0.008). figure 3: molecular weight distribution of proteins with 1.5-3.0 fold change in patients with temporal lobe epilepsy (tle) and psychogenic non-epileptic seizure (pnes) (p = 0.05). expressed in the hippocampus of these patients compared to the control. however, only nine proteins were identified in this study. among the nine deregulated proteins, six were upregulated while one of them was down-regulated in the tle group compared to controls. the other two proteins were only identified in the 2d-page of epilepsy patients. in recent decades, new proteomics technologies have been developed to help us find appropriate protein biomarkers in serum. simultaneous changes in many proteins in this disease can indicate biochemical mechanisms involved in its incidence, which can be effective for medicinal purposes in the treatment process. few studies have measured and compared pi/mw of proteins whose expression significantly changed in temporal lobe epileptic patients and pi/mw in data base (31, 32). by measuring pi and molecular weight, behboodi et al. reported that a more malignant cancer is associated with a more acidic pi and lower molecular weight for proteins detected in tissue (33). further studies are needed to identify this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. parvareshi hamrah et al. 6 differentially expressed proteins between the two groups. 5. conclusion it can be concluded that blood brain barrier damage in epileptic seizures is the main event that can discriminate pnes patients from es individuals. therefore, identification of the deregulated proteins will provide a clear perspective of es. 6. declarations 6.1. acknowledgements the authors would like to thank the proteomics research center, shahid beheshti university of medical sciences, tehran, iran for their support, cooperation and assistance throughout the study. 6.2. authors’ contribution all authors had equal role in design, work, statistical analysis, and manuscript writing. authors orcids mohsen parvareshi hamrah: 0000-0002-9209-9348 mostafa rezaei tavirani: 0000-0003-1767-7475 6.3. funding/support this study was funded by proteomics research center, shahid beheshti university of medical sciences. 6.4. conflict of interest the authors declare that they have no conflict of interest. 6.5. human and animal rights all procedures performed on human subjects this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 helsinki declaration and its later amendments or comparable ethical standards. additionally, ethics committee of shahid beheshti university of medical sciences approved this study by ir.sbmu.retech.rec.1397.289. 6.6. informed consent informed consent was obtained from all individual participants included in the study. references 1. bodde nm, brooks jl, baker ga, boon pa, hendriksen jg, aldenkamp ap. psychogenic non-epileptic seizures– diagnostic issues: a critical review. clinical neurology and neurosurgery. 2009;111(1):1-9. 2. gedzelman er, laroche sm. long-term video eeg monitoring for diagnosis of psychogenic nonepileptic seizures. neuropsychiatric disease and treatment. 2014;10:1979. 3. gordon pc, valiengo ldcl, proenca ic, kurcgant d, jorge cl, castro lh, et al. comorbid epilepsy and psychogenic non-epileptic seizures: how well do patients and caregivers distinguish between the two. seizure. 2014;23(7):537-41. 4. bodde n, brooks j, baker g, boon p, hendriksen j, mulder o, et al. psychogenic non-epileptic seizures–definition, etiology, treatment and prognostic issues: a critical review. seizure. 2009;18(8):543-53. 5. lafrance jr wc, reuber m, goldstein lh. management of psychogenic nonepileptic seizures. epilepsia. 2013;54:53-67. 6. chmielewska n, szyndler j, makowska k, wojtyna d, maciejak p, plaznik a. looking for novel, brain-derived, peripheral biomarkers of neurological disorders. neurologia i neurochirurgia polska. 2018;52(3):318-25. 7. shahrokh s, razzaghi z, mansouri v, ahmadi n. impact of proteomics in laser therapy of skin: a review article. journal of lasers in medical sciences. 2019;10(4):90-5. 8. wilkins mr, sanchez j-c, gooley aa, appel rd, humphery-smith i, hochstrasser df, et al. progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. biotechnology and genetic engineering reviews. 1996;13(1):19-50. 9. wilkens s, zhang z, zheng y. a structural model of the vacuolar atpase from transmission electron microscopy. micron. 2005;36(2):109-26. 10. ashrafmansouri m, sadjjadi fs, seyyedtabaei s, haghighi a, rezaei-tavirani m, ahmadi n. comparative twodimensional gel electrophoresis maps for amastigotelike proteomes of iranian leishmania tropica and leishmania major isolates. galen medical journal. 2019;8:1520. 11. fayazfar s, zali h, oskouie aa, aghdaei ha, tavirani mr, mojarad en. early diagnosis of colorectal cancer via plasma proteomic analysis of crc and advanced adenomatous polyp. gastroenterology and hepatology from bed to bench. 2019;12(4):328. 12. riquelme a, valdes-tovar m, ugalde o, maya-ampudia v, fernãąndez m, mendoza-durãąn l, et al. potential use of exfoliated and cultured olfactory neuronal precursors for in vivo alzheimer’s disease diagnosis: a pilot study. cellular and molecular neurobiology. 2020;40(1):87-98. 13. da silva fernandes mj, amorim rp, carneiro jem, araujo mgl, persike ds. proteomics-based strategy to identify biomarkers and pharmacological targets in temporal lobe epilepsy. pharmacoresistance in epilepsy: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e18 springer; 2013. p. 115-26. 14. azadegan-dehkordi f, bagheri n, shirzad m, sanei mh, hashemzadeh-chaleshtori m, rafieian-kopaei m, et al. correlation between mucosal il-6 mrna expression level and virulence factors of helicobacter pylori in iranian adult patients with chronic gastritis. jundishapur journal of microbiology. 2015;8(8). 15. ehsan t, fisher rs, johns d, lukas rj, blum d, eskola j. sensitivity and specificity of paired capillary prolactin measurement in diagnosis of seizures. journal of epilepsy. 1996;9(2):101-5. 16. anzola gp. predictivity of plasma prolactin levels in differentiating epilepsy from pseudoseizures: a prospective study. epilepsia. 1993;34(6):1044-8. 17. tunca z, ergene u, fidaner h, cimilli c, ozerdem a, alkin t, et al. reevaluation of serum cortisol in conversion disorder with seizure (pseudoseizure). psychosomatics. 2000;41(2):152. 18. bakvis p, spinhoven p, giltay ej, kuyk j, edelbroek pm, zitman fg, et al. basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures. epilepsia. 2010;51(5):752-9. 19. willert c, spitzer c, kusserow s, runge u. serum neuronspecific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures. acta neurologica scandinavica. 2004;109(5):318-23. 20. lafrance w, leaver k, stopa e, papandonatos g, blum a. decreased serum bdnf levels in patients with epileptic and psychogenic nonepileptic seizures. neurology. 2010;75(14):1285-91. 21. aydin s, dag e, ozkan y, arslan o, koc g, bek s, et al. time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients. peptides. 2011;32(6):1276-80. 22. sundararajan t, tesar g, jimenez x. biomarkers in the diagnosis and study of psychogenic nonepileptic seizures: a systematic review. seizure. 2016;35:11-22. 23. li t, bourgeois j-p, celli s, glacial f, le sourd am, mecheri s, et al. cell-penetrating anti-gfap vhh and corresponding fluorescent fusion protein vhh-gfp spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging. the faseb journal. 2012;26(10):3969-79. 24. muruganandam a, tanha j, narang s, stanimirovic d. selection of phage-displayed llama single-domain antibodies that transmigrate across human blood–brain barrier endothelium. the faseb journal. 2002;16(2):240-2. 25. yang j, czech t, yamada j, csaszar e, baumgartner c, slavc i, et al. aberrant cytosolic acyl-coa thioester hydrolase in hippocampus of patients with mesial temporal lobe epilepsy. amino acids. 2004;27(3-4):269-75. 26. bandtlow ce, dlaska m, pirker s, czech t, baumgartner c, sperk g. increased expression of nogo-a in hippocampal neurons of patients with temporal lobe epilepsy. european journal of neuroscience. 2004;20(1):195-206. 27. yang j, czech t, felizardo m, baumgartner c, lubec g. aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. amino acids. 2006;30(4):477-93. 28. danis o, demir s, gunel a, aker rg, gulcebi m, onat f, et al. changes in intracellular protein expression in cortex, thalamus and hippocampus in a genetic rat model of absence epilepsy. brain research bulletin. 2011;84(6):381-8. 29. lo w-y, tsai f-j, liu c-h, tang n-y, su s-y, lin s-z, et al. uncaria rhynchophylla upregulates the expression of mif and cyclophilin a in kainic acid-induced epilepsy rats: a proteomic analysis. the american journal of chinese medicine. 2010;38(04):745-59. 30. conboy l, varea e, castro je, sakouhi-ouertatani h, calandra t, lashuel ha, et al. macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors. molecular psychiatry. 2011;16(5):533. 31. eun j-p, choi h-y, kwak y-g. proteomic analysis of human cerebral cortex in epileptic patients. experimental & molecular medicine. 2004;36(2):185. 32. lee cw, yu st, choi hy, koh bj, kwak yg. proteomic analysis of human serum from patients with temporal lobe epilepsy. korean journal of pediatrics. 2009;52(5):567-75. 33. behboodi f, tavirani mr, yousefzadeh s, bashizadehfakhar h, ashoorizadeh b, faraji r, et al. studying the proteomic pattern of cancerous tissue in patients with breast cancer and its’ comparing with healthy breast. zahedan journal of research in medical sciences. 2015;17(11). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 165 emergency (2015); 3 (4): 165-167 casr report an immediate death by seat belt compression; a forensic medicine report fares najari1*, ali mohammad alimohammadi2 1. department of forensic medicine, shahid beheshti university of medical sciences, tehran, iran. 2. center of forensic medicine researches, forensic legal medicine organization, tehran, iran. *corresponding author: fares najari; department of forensic medicine; shohadaye tajrish hospital, tehran, iran. tel: 00989123195140 email: fares.hospital@yahoo.com received: may 2015; accepted: june 2015 abstract although death is a gradual process, sometimes sudden death occurs in a fraction of a minute or seconds. here we report a 49-year-old man without any underlying disease, which has instantly died in an accident scene due to compression of neck critical elements by a three-point seat belt. the examination of the body and the results of the autopsy, toxicology and pathology tests are described from the viewpoint of forensic medicine. key words: seat belts; accidents, traffic; death; sudden cite this article as: najari f, alimohammadi am. an immediate death by seat belt compression; a forensic medicine report. emergency. 2015;3(4):165-7. introduction: enerally, a safety belt is essential during driving and often decreases the mortality rate of the passengers up to 50-75%. the majority of articles have been written about their benefits only, but it is also undeniable that in the case of improper use, seat belts can even be dangerous and life-threatening (1-4). the following report presents a rare mortality case with fatal asphyxia caused by the seat belt, referred to forensic department. here the examination of the body and the results of the autopsy, toxicology and pathology tests are described from the viewpoint of forensic medicine. case report: the deceased was described as a 49 year old man who was driving with a high speed of 110 kilometers per hour, in a highway in tehran. his car had been hit hard from behind by another car. he died instantly without collision with the dashboard, steering wheel or any other part of the car according to the statement of the car passenger. the body belonged to a 49-year-old male, weighting approximately 85 kilograms, height 175 centimeters, with formal clothing and was examined in tehran forensic autopsy center. rigor mortis had been established and bruises with natural color were developed on the posterior surfaces of the body. putrefaction was not evident. examination: time of death was estimated to be within the last 24 hours. in the examination, the deceased was in relatively good health and adornment. on the head and face, there were no signs of assaults, pressure around the mouth and nose, congestion, conjunctival hyperemia and petechiae in the eye, foreign body in the mouth, or bone fracture. face was pale. on the neck, strip-like bruises were visible on the left side. on the trunk, strip printed abrasion was seen starting from the upper left shoulder and extending diagonally to the right side (possibly the pressure of the seat belt). cardiopulmonary resuscitation signs weren't seen on the chest. on the extremities, abrasions were visible on the dorsum of the left wrist and anterior of the right forearm, abrasions and bruises were present on anterior right forearm and right groin. defensive injuries, electrical signs, fracture and dislocation of joints weren’t visible and tangible. signs of injections weren’t found. there was nothing abnormal in the genitals and anus. autopsy: grossly, the scalp was cut. there were no evidence of scalp and temporal muscle hematomas. the vault of the skull was removed. brain tissue was normal in appearance. no signs of intracranial hemorrhage (ich), intraventricular hemorrhage (ivh), sub-arachnoid hemorrhage (sah), brain contusion, and space-occupying mass lesion were seen. dura was removed. skull base fracture wasn’t evident. the skin was cut from the chin to the pubic. hematomas were evident under the skin and between the muscles in accordance with the striplike abrasions and massive bruises in the left intercostal muscle, in addition to hematomas on left side of neck and left anterior shoulder. the hyoid bone and thyroid cartilage in the neck were normal. in cutting the throat and larynx and trachea, hematomas were visible around the muscles of the left side of throat and larynx. there g this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com najari et al 166 was no sign of fracture and dislocation in larynx or foreign body in the airway. pharynx and larynx were removed. fracture and dislocation of the cervical spine weren’t found. the body was also assessed in prone position and in autopsy of posterior spinal and dorsal cervical spine, no pathologic finding was found. sternum and part of costal cartilages were pushed to the side. no abnormal peripheral blood or fluids were detected in the two sides of thoracic cavity. lungs were congested in appearance and had a spongy consistency when touched and had no edema at the cutting. pericardium was cut. blood or other abnormal fluids were not found. the heart was removed from the base of the vessel. the weight was normal. there was an increased amount of fat around the heart. aortic opening was normal and without atheromatic plaques. in the main coronary arteries, atherosclerotic stenoses were absent with a normal consistency and in slicing the heart muscle, fibrosis and hyperemia weren’t evident. the abdominal cavity was open with no blood or other abnormal fluids. in the intra-abdominal organs, liver and spleen were normal and were not teared. stomach had normal mucosa and contained semi-digested food. intestinal rupture or perforation, necrosis or nigrescence and foreign body weren’t observed. there was no retroperitoneal hematomas. the kidneys were normal. urinary bladder contained urine. other intra-abdominal organs were deployed without disruption to their anatomical location. to determine the cause of death, pathology specimen were obtained from heart, lung, brain, and cerebellum. in addition, vitreous, urine, bile, gut, and stomach samples were evaluated from toxicologic viewpoint. finally, based on the results of examination, autopsy, and toxicology, the compression of neck critical elements such as carotid sinus was determined as the cause of death. discussion: in addition to the speed, the road type, and the mechanism of the accident, type of the belt is also important in causing injuries (1, 2). there are different types of safety belts in vehicles including femoral belts, diagonal belts (shoulder) and three-point seat belts (thigh and shoulder) (3, 5, 6). femoral belts were first popularized in australia in 1964 (7). these belts are now used in the rear seats, and all new cars have three-point seat belts. if the femoral belt is fastened too high and placed on top of the hips, it can cause fracture on the body of vertebrate and transverse processes. improper use of this type of seat belt can also lead to soft tissue injuries and even small bowel perforation and rupture of solid organs (8, 9). while all of these injuries are caused by higher fastening of the safety belts, even with the proper use of seat belts crossing over neck can happen. in this case, hip goes lower at the time of the collision of seat and slides under seat belt. however, most abdominal cavities and spinal cord injuries are due to high fastening of seat belt (10-12). any damage to the small intestine and colon and lumbar spine at the level of safety belt is called safety belt syndrome, abrasion and laceration of the abdominal wall is also common and is seen in 30% of patients and has been first reported by braunstein, garrett. by using three-point belts, collision with the dashboard and steering wheel will be avoided. however, this belt type may lead to fracture of ribs, sternum and clavicle and neck vertebrae; strangulation and hanging on the left side of the car have also been reported (13-15). a diagonal abrasion across the chest is usually associated with a three-point belt accompanied with fracture of ribs, sternum and clavicle in severe accidents and may also be associated with rupture of the aorta and ventricle of the heart and might cause vascular and tracheal and laryngeal lesions in the neck (16). horizontal fractures caused by femoral belts in the second and third lumbar vertebrae was first reported in 1948 by chance and fracture of c7-t1 transverse process have been reported in using three-point seat belts. in the three-point seat belts, the most common lesions are mesenteric rupture and rupture of vessels in the mesentery of the small intestine, additionally a colon rupture at the anti-mesenteric region related to jejunum and ileum were reported. in an article by kirk patrick, 68 cases out of 82 patients had lesions in the small intestine and 19 had colonic injuries (11, 13-15). richard bands et al. in 2011 reported that from a total of 130 patients with lesions caused by the seat belt, only 34 patients had cervical lesions (24 had soft tissue lesions) and 10 patients had neck fracture, all of which were associated with application of the three-point seat belts (16, 17). in the presented case, if the speed of the car was in the allowed range and safety belt was properly used, driver's immediate death would not have happened. therefore, it is necessary to use the seat belt as a savior in the drivers, but we should not neglect the application of the standards of driving and the speed of the vehicle or else this very simple and valuable tool can change into a destructive one. conclusion: it seems that, compression of neck critical elements such as carotid sinus by a three-point safety belt could be a rare potential cause of instant death following car accidents. acknowledgment the authors appreciate the insightful cooperation of staff of the forensic dissection of tehran conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribu this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 167 emergency (2015); 3 (4): 165-167 tion based on recommendations of the international committee of medical journal editors. references: 1. al-ghamdi as. pedestrian–vehicle crashes and analytical techniques for stratified contingency tables. accident anal prev. 2002;34(2):205-14. 2. rosman dl. the western australian road injury database (1987–1996):: ten years of linked police, hospital and death records of road crashes and injuries. accident anal prev. 2001;33(1):81-8. 3. houston dj, richardson le. the politics of air bag safety: a competition among problem definitions. policy stud j. 2000;28(3):485-501. 4. soori h, nasermoadeli a, movahedi m, et al. the effect of mandatory seat belt use legislations on mortalities from road traffic injuries in iran. hakim research journal. 2009;12(1):48-54. 5. knight b. forensic pathology. 2 ed. london: taylor & francis; 1996. 154 p. 6. skaga no, eken t, hestnes m, jones jm, steen pa. scoring of anatomic injury after trauma: ais 98 versus ais 90—do the changes affect overall severity assessment? injury. 2007;38(1):84-90. 7. fenner p. surf life saving australia. j south pacific underwater med soc. 2005;35(1): 33-43. 8. abu-zidan fm, eid ho. factors affecting injury severity of vehicle occupants following road traffic collisions. injury. 2015;46(1):136-41. 9. afifi i, el-menyar a, al-thani h, peralta r. seatbelt versus seatbelt and airbag injuries in a single motor vehicle crash. int j crit illn inj sci. 2015;5(1):46-9. 10. nantulya vm, reich mr. the neglected epidemic: road traffic injuries in developing countries. bmj. 2002;324(7346):1139. 11. ameratunga s, hijar m, norton r. road-traffic injuries: confronting disparities to address a global-health problem. lancet. 2006;367(9521):1533-40. 12. sharma b. road traffic injuries: a major global public health crisis. public health. 2008;122(12):1399-406. 13. akbari m, naghavi m, soori h. epidemiology of deaths from injuries in the islamic republic of iran. east mediterr health j. 2006;12(3-4):382-90. 14. naghavi m, abolhassani f, pourmalek f, et al. the burden of disease and injury in iran in the year 2003. iran j epidemiol. 2008;4(1):1-19. 15. perry ar, baldwin da. further evidence of associations of type a personality scores and driving-related attitudes and behaviors. percept and motor skills. 2000;91(1):147-54. 16. clarke s, robertson i. a meta-analytic review of the big five personality factors and accident involvement in occupational and non-occupational settings. j occup organ psychol. 2005;78(3):355-76. 17. peden m. world report on road traffic injury prevention. world health organization geneva; 2004. introduction: enerally, a safety belt is essential during driving and often decreases the mortality rate of the passengers up to 50-75%. the majority of articles have been written about their benefits only, but it is also undeniable that in the case of improper use... case report: the deceased was described as a 49 year old man who was driving with a high speed of 110 kilometers per hour, in a highway in tehran. his car had been hit hard from behind by another car. he died instantly without collision with the dashboard, steerin... examination: time of death was estimated to be within the last 24 hours. in the examination, the deceased was in relatively good health and adornment. on the head and face, there were no signs of assaults, pressure around the mouth and nose, congestion, conjunctiv... autopsy: grossly, the scalp was cut. there were no evidence of scalp and temporal muscle hematomas. the vault of the skull was removed. brain tissue was normal in appearance. no signs of intracranial hemorrhage (ich), intraventricular hemorrhage (ivh), sub-ara... discussion: conclusion: it seems that, compression of neck critical elements such as carotid sinus by a three-point safety belt could be a rare potential cause of instant death following car accidents. acknowledgment the authors appreciate the insightful cooperation of staff of the forensic dissection of tehran conflict of interest: funding support: authors’ contributions: references: emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 59 emergency (2014); 2 (2): 59-65 reveiw development of an easy-to-use tool for the assessment of emergency department physical design alireza majidi1, ali tabatabaey1*, hassan motamed2, maryam motamedi1, mohammad mehdi forouzanfar1 1. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran abstract physical design of the emergency department (ed) has an important effect on its role and function. to date, no guidelines have been introduced to set the standards for the construction of eds in iran. in this study, we aim to devise an easy-to-use tool based on the available literature and expert opinion for the quick and effective assessment of eds in regards to their physical design. for this purpose, based on current literature on emergency design, a comprehensive checklist was developed. then, this checklist was analyzed by a panel consisting of heads of three major eds and contradicting items were decided. 178 crude items were derived from available literature. the items were categorized in to three major domains of physical space, equipment, and accessibility. the final checklist approved by the panel consisted of 163 items categorized into six domains. each item was phrased as a “yes or no” question for ease of analysis, meaning that the criterion is either met or not. key words: emergency department; facility design and construction; checklist; hospital planning cite this article as: majidi a, tabatabaey a, motamed h, motamedi m, forouzanfar mm. development of an easy-to-use tool for the assessment of emergency department physical design. emergency. 2014;2(2):59-65. introduction:1 designing an emergency department (ed) is a complex and time consuming effort (1). a proper design should consider facilitating treatment processes and workflow, future development, changes in target population, and natural disasters; while attending to important issues such as safety, security, privacy, accessibility, costumer expectations, and aesthetic attractiveness is crucial. the design is affected by the number of people expected to work and receive services in each space (2). emergency design is also an integral part of any attempt at improving patient flow. more and more ed expansions focus on increasing the number of beds without attention to the workflow. this is not always an efficient tactic. it appears that designing smaller functional units within a larger department may be a better design strategy. such units should include a place for physicians and nurses station, a secretary work station, space for lab specimens, a portal for the tube system, a medication room, a viewing area for radiology results, and both clean and dirty utility rooms (3). while many countries have introduced guidelines to clarify the minimum requirements in this process (2, 4), iran has yet to embrace such a document. generally, before designing an ed one *corresponding author: ali tabatabaey, department of emergency medicine, shohadaye tajrish medical center, tajrish square, tehran, iran phon/fax: 0098-2122721155. email: alitabtab@gmail.com received: 2 march 2014; accepted: 12 april 2014 must have a vision of the magnitude of services to be provided. this can be achieved by attaining indices such as annual census of patients and their demographics, average daily admissions, peak admissions, peak times, triage system in place, rate of patients requiring critical care and monitoring, average times of stay in the ed, and plans for future development (2). such static quantitative and quantitative estimates have been the basis for planning ed expansions, but the use of a qualitative dynamic systems is offering new information to planners and designers (5). another emerging concept is evidence-based design in which the effects of ed design on patient satisfaction, functionality, medical errors, and side effects. in this type of design energy consumption is studies and the results guide future design plans (6). in this study, we aim to devise an easy-to-use tool based on the available literature and expert opinion for the quick and effective assessment of eds in regards to their physical design. methods: this was a qualitative developmental study aimed at improving the tools for assessment of the physical aspects of ed design and offering exact suggestions for improvement. initially a search for current literature on emergency design was conducted using the following string on pubmed, google scholar, and google search engines: “emergency department” and “physical design” or design or “architectural design”. a snowball this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidi et al 60 method was then used to further expansion of literature using references of search results. the obtained information was then reviewed and data was rewritten as short clear items. the items were reviewed, and repeated items were omitted. contradicting items from different sources were marked and listed as a single item. next the items were classified into general domains to help organized the checklist. in the second step of the study, this checklist was analyzed by a panel consisting of heads of three major eds. the experts reviewed the items and domains. contradicting items were decided upon based on the version most applicable to the current situation of eds in iran. some items irrelevant to the iranian landscape were deleted and others were adjusted to fit better with domestic needs. other items were better clarified and in rare occasions, new items were added to address issues not covered in the literature. results: 178 crude items were derived from available literature. the items were categorized in to three major domains of physical space, equipment, and accessibility. the preliminary checklist was then referred to the panel of expert where it was modified to fit the current iranian needs and resources. the final checklist approved by the panel consisted of 163 items categorized into six domains (table 1). each item was phrased as a “yes or no” question for ease of analysis, meaning that the criterion is either met or not. discussion: access to healthcare is a constitutional right for all patients and the ed serves as a gateway to treatment services. the importance of a well-functioning ed is reflected in the fact that 30 to 40% of hospital admissions come through the ed, while over three-quarters of patients base their impression of a hospital on an ed experience (7). the ed is often host to a wide range of patients and personnel who’s optimal functionality relies on a proper physical design (8). an ed should be designed and equipped in a way that is accessible, provides a safe environment for the patients, respects patient privacy, and incorporates complementary services such as laboratory and radiology units (9). to optimize ed functionality good processes must be merged with good design (3, 10). in this regard several suggestions have been made (1, 2, 5, 11). although every ed requires a unique design scheme, guidelines have been introduced to clarify the minimum requirements for a functional department (2). these guidelines are often lengthy and while helpful in guiding design, they lack the simplicity required for quick assessment of working eds. in iran and other countries in the middle east, great attention is being aimed at improving currently working eds and optimizing their functionality. we believe that the results of this study give healthcare managers the tool needed for fast and precise decisionmaking regarding ed expansions and development. assessment with the devised checklist was able to bring attention to some major flaws within the emergency design. the hallmark of ed design is congruency between infrastructure and patient load. the emergency department benchmarking alliance (edba) has suggested that new eds should have the capacity to treat 1500 patients per year in each treatment area (10). other guidelines indicate 50m2 of ed area for every 1000 patients, or 145m2 for every 1000 patients admitted (whichever is more) (2). patient and personnel privacy was another concept emphasized by the expert panel. research has shown that 5% of patients withhold important information in the history because they feel their privacy might be breached (8). many personnel also believe that patient privacy is often breached within the ed (12). improving physical design is one way to improve patient privacy whenever possible (13). the traditional ed design incorporates the concept that all patients must be within eyesight of the station. this includes patients with different levels of acuity. recent studies have suggested that creating patient tracks based on acuity will help alleviate such conditions for the “not so sick” patient. therefore such a design should only be used for more acute patients (3). new emergency physicians are graduating each year and are taking over eds around the country. this has led to a wave of reform within eds. eds are being upgraded to meet with increasing demands of both patients and management. in this setting, lack of a national guideline for design of eds is confusing and complicates the process of assessment and auditing of these important institutions. the development and finalization of a quick and easy-to-use checklist for the assessment of eds can help simplify the task of planning physical expansion of eds by focusing attention on the criteria that will have the greatest effect. we believe that the results of this study can be the initial step towards composing such a document. acknowledgments: we acknowledge all staffs of emergency department of shohadaye tajrish hospital, tehran, iran. conflict of interest: the authors have no conflicts to declare funding support: this research has been funded by academic grants from shahid beheshti university of medical sciences (number: 89-01-120-7345). authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 61 emergency (2014); 2 (2): 59-65 references: 1. brenner i. building a better emergency department: an architect’s perspective. emergency physicians monthly [internet]. 2010. available from: http://www.epmonthly.com/archives/features/building-abetter-emergency-department-an-architects-perspective/>. 2. guidelines on emergency department design. australasian colledge for emergency medicine, 2007 g12. 3. welch sj. using data to drive emergency department design: a metasynthesis. health envir res design j. 2012;5(3): 26-45. 4. salluzzo rf, mayer ta, strauss rw, kidd ps. emergency department management: principles and applications: mosby; 1997. p. 230-350. 5. exadaktylos ak, evangelopoulos ds, wullschleger m, burki l, zimmermann h. strategic emergency department design: an approach to capacity planning in healthcare provision in overcrowded emergency rooms. j trauma manag outcomes. 2008;2(1):11-9. 6. evitts ea. hospital emergency department plans. architect magazine [internet]. 2007. available from: http://www.architectmagazine.com/healthcareprojects/rethinking-the-er-emergency-room-layoutdesign_1.aspx. 7. exadaktylos ak, velmahos gc. emergency medicine and acute care surgery: a modern "hansel and gretel" fairytale? emerg med j. 2008;25(6):321-2. 8. ulrich r, zimring c. the role of the physical environment in the hospital of the 21st century: a once-in-a-lifetime opportunity. the center for health design for the designing the 21st century hospital project, 2004. 9. emergency department planning and resource guidelines. annals of emergency medicine. 2005;45(2):231-8. 10. huddy j. emergency department design. freemanwhite company; 2012. 11. transforming the emergency department solution essay. hermanmiller healthcare 2009. 12. calleja p, forrest l. improving patient privacy and confidentiality in one regional emergency department — a quality project. australasian emergency nursing journal 2011;14:251-6. 13. lin yk, lee wc, kuo lc, et al. building an ethical environment improves patient privacy and satisfaction in the crowded emergency department: a quasi-experimental study. bmc med ethics. 2013;14:8. http://www.epmonthly.com/archives/features/building-a-better-emergency-department-an-architects-perspective/%3e http://www.epmonthly.com/archives/features/building-a-better-emergency-department-an-architects-perspective/%3e http://www.architectmagazine.com/healthcare-projects/rethinking-the-er-emergency-room-layout-design_1.aspx http://www.architectmagazine.com/healthcare-projects/rethinking-the-er-emergency-room-layout-design_1.aspx http://www.architectmagazine.com/healthcare-projects/rethinking-the-er-emergency-room-layout-design_1.aspx this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidi et al 62 table 1: suggested checklist for assessment of emergency department design  accessibility yes no 1. is the emergency department located within the main hospital building? 2. is the ed entrance the most easily accessed entrance of the hospital? 3. is the ed easily accessed from the parking? 4. are there special parking areas reserved for on call physicians close to the entrance? 5. is the entrance to the emergency department clearly visible and marked? 6. is there separate entrance ports for ems and walk-in patients? 7. is the walk-in entrance easily visible for public? 8. is the triage room clearly visible and in the path of walk-in patients entrance? 9. is the way to the triage room clearly depicted by lines or lights? 10. is there a line system to guide patients to different areas of the ed? 11. is the emergency reception area (ems, walk-in, waiting room) easily recognized? 12. are the entrance ports and the waiting area in direct observation field of the triage nurse? 13. is the treatment easily and quickly accessible from the reception area? 14. is a cardiac resuscitation area quickly accessible from the emergency entrance? 15. is the critical care area in direct access of the treatment area, waiting room, and the reception area? 16. is access to a trauma care area quickly feasible from the entrance? 17. is there easy access to the ccu, icu, and or from the ed? 18. is the access to the or and icu possible without passing through crowded or unroofed areas? 19. are dedicated elevators available if these facilities are not in the same level as the ed? 20. is there easy access to main hospital hallways for ease of patient transport to floors? 21. are the orthopedic examination and casting rooms away from the main treatment areas? 22. are the orthopedic examination and casting rooms close to the radiology suit? 23. in ed with more than 50000 annual admissions, does the imaging area have different entrance ports for ed patients and patients referred from the rest of the hospital? 24. is there a scrub station close to the trauma or orthopedic rooms? 25. is there direct access to the imaging suit, and the resuscitation room form the treatment area? 26. is the emergency lab easily accessible from all treatment areas? 27. is there a different window for delivery of emergent lab samples at the laboratory? 28. is there access to the psychiatric ward within the same building as the ed? 29. is there a psychiatric room close to the ems entrance? 30. is the nurses’ station located in a manner to oversee all patients either directly or indirectly? 31. is the nursing station integrated and free of any major obstacles? 32. is the equipment in the nursing station readily and easily accessible to the nursing staff? 33. is patient access to treatment equipment properly limited? 34. have all objects of more than 1m height been removed from the observation field of the nurse’s station? 35. is direct observation of the pediatric care area by treatment staff possible at all times? 36. are there washrooms close to isolated treatment rooms such as the obstetrics and gynecology (obgyn) room? 37. are the fire exits easily accessible and clearly depicted? 38. are all doors in the ed at least 1.5m wide? 39. do the reception and waiting areas have direct access to the hospital for outpatient referral? 40. are the outpatient care, ophthalmology, and otolaryngology areas adjacent to the entrance? 41. does the security station have a 360◦ view of the immediate emergency department? 42. is the police station equipped with cctv cameras to oversee every part of the emergency department? physical spaces, structures, and equipment 1. is the ed building able to endure a severe earthquake? 2. is the total area of the ed sufficient relative to annual patient admissions? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 63 emergency (2014); 2 (2): 59-65 table 2: continue… yes no 3. are the number of beds sufficient relative to the number of annual admissions? 4. are there sufficient number of isolated treatment rooms relative to annual admissions? 5. are the number of beds for low-acuity patients sufficient relative to the number of annual patient load? 6. is the overall size of the department at least one and half times the emergent and low-acuity treatment areas? 7. are there sufficient number of washrooms relative to the number of treatment beds? 8. are there areas within the ed, which can be transformed to treatment areas in order to improve surge capacity? 9. is there a decontamination area and shower adjacent to the entrance? 10. are there electrical outlets and service panels available outside the ed entrance? 11. is there a specific room for patients’ triage? 12. is the triage designed in a way to allow two nurses to conduct triage simultaneously? 13. is the triage and reception area large enough relative to the number of annual admissions? 14. are there dedicated examination rooms for pediatric patients? 15. is there a fast track area in the ed? 16. is there an isolated ob-gyn room for treatment? 17. is the ob-gyn room acoustically isolated and equipped properly? 18. is there a dedicated washroom available within the ob-gyn room? 19. is there an orthopedics and casting room in the ed? 20. is there a procedure or minor operating room designated in the ed? 21. is the procedure room equipped properly with monitory devices, lights, etc.? 22. is security stationed in the ed located at the entrance? 23. is there a treatment area for walk-in patients? 24. is there a pharmacy in the ed or near it? 25. is there men and women washrooms in the reception area? 26. is there an area with access to medical information in the reception area? 27. is there an isolated room for treatment of infectious disease? 28. is there a lab and blood bank in the emergency department? 29. is there a room for ent treatment? 30. is the ent room equipped properly? 31. is there a room for ophthalmologic examination and treatment? 32. is the ophthalmology room equipped properly? 33. is there a waiting area? 34. is there a dedicated area in the core areas for changing gowns, gloves, masks and wash up? 35. is there a head nurse room in the ed? 36. is there a burn care room in the ed? 37. is there a grief room in the ed? 38. is there a department head office in the ed? 39. is there a designated administration area away from the treatment areas? 40. is there a silent or counseling room designated within the ed? 41. is the counseling room acoustically isolated from the treatment areas? 42. is there a morgue? 43. are gurneys available at the ed entrance? 44. are gurney heights 75cm? 45. is there at least 11.15m2 dedicated to each bed in the treatment area? 46. is there at least 7.43m2 dedicated to each low-acuity bed? 47. are there outpatient care areas of 0.5 to 2.3m2 areas? 48. is the trauma room at least 23×23 m2? 49. is the critical care and cpr room at least 23×23 m2? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidi et al 64 table 3: continue… yes no 50. is the nursing station counter at least 1 meter in height? 51. is there an emergency backup electricity supply for the ed? 52. is there a proper and separate air-cycling system installed for each treatment area? 53. is there a separate air-cycling system for each isolated treatment room? 54. are there separating wooden panels from ceiling to the floor available in the treatment area? 55. can the panels be removed to increase the available treatment area? 56. is there sufficient lighting in the examination and treatment areas? 57. is there an examination table available in the outpatient treatment areas? 58. is continuous monitoring of the isolated treatment rooms possible? 59. is there a central o2 supplying system with outlets available at least for every high-acuity bed? 60. are suction equipment (fixed or portable) available for each bed in the treatment area? 61. is there a sanitation sink available in each treatment area? 62. is there access to multiple phone lines in the nurses’ station? 63. is there access to the internet in the ed? 64. is there access to a phone line in the waiting area? 65. is there a telecom system installed in the ed? 66. are the washrooms equipped with functioning call-for-help systems? 67. is there a cpr paging system in place? 68. is there a fire alarm system installed in different areas of the ed? 69. are fire extinguishers available in all ed spaces? 70. are enough electrical outlets available in each treatment area? 71. are the electrical outlets properly placed at a height of 36cm? 72. is there a danger alarm to call in security in the ed? 73. is there a portable x-ray available in the cpr room? 74. is the lab equipped for routine lab tests (cbc, electrolytes, blood glucose, urinalysis, urea, creatinine, pregnancy test, blood gas analysis)? 75. is there facilities for continuous security monitoring of the different treatment and working areas? 76. is there proper storages for clean and dirty equipment within the ed? patient accommodations 1. is there sufficient waiting area relative to the annual number of admissions? 2. is there assistance available at reception for patients unable to care for themselves? 3. is there a functioning air-conditioning system in the waiting area? 4. is there a drinking fountain in the reception area? 5. are there sufficient seats in the waiting area relative to the annual number of admissions? 6. is there a public phone in the reception? 7. are reading materials available in the reception area? 8. is there entertainment available in the waiting area? 9. is there a functioning air-conditioning system is the treatment areas? 10. is there a nurse paging system available for each bed? 11. does the acute treatment area have a high ceiling? 12. does the waiting area enjoy abundant lighting, and natural colors? 13. does the low-acuity treatment area have a lower ceiling, lower lights, acoustic instillations, and light colors? 14. is the waiting area equipped with sufficient accessories? 15. is there a system available within the ed to supply patients with their personal needs? 16. is there a playroom for pediatric patients? 17. are seats available for persons accompanying patients in the treatment areas? 18. is there a prayer room with access to the waiting area for patients and people accompanying them? this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 65 emergency (2014); 2 (2): 59-65 table 4: continue… yes no personnel accommodations 1. is there a dedicated area for viewing imaging results? 2. is there a distinct physicians resting area? 3. is there a resting room area sufficient relative to the number of personnel? 4. is there air-conditioning available in the resting area? 5. is there easy access to the restroom and lockers from the resting area? 6. is the personnel resting area close to the core areas? 7. is the resting area equipped with washrooms? 8. is the resting area equipped with a personnel shower? 9. is the resting area equipped with refrigerators, sink, and microwave? 10. is the resting area equipped with proper communication facilities such as phone and internet? 11. is there a dining area located within the resting area? 12. is there a sleeping area located within the resting area? 13. is there sufficient lighting in the resting area? 14. is there a praying room designated within the resting area? patient privacy 1. is there a discrete physical examination area designated? 2. is the patients’ visual, auditory, and olfactory privacy securable within each treatment area? 3. is the path to the elevator separate from the main crowded areas? 4. is there a designated area for storing patient files away from other patients’ reach? 5. does the ob-gyn room have a fully private setup in the more secluded parts of the ed? 6. is there an area suitable for discrete exchange of information between the staff? 7. is there a designated area for confidential patient-doctor interactions? personnel privacy 1. is the personnel working area properly isolated from the patients care area? 2. are the changing and locker areas away from patient care areas? 3. is the resting area away from patients’ sight? 4. is there a proper area for storing the staff’s personal belongings? 5. is there a designated area for confidential doctor-doctor conversations both in person and by phone? 6. is there a separate entrance and exit for staff? emergency. 2018; 6 (1): e6 or i g i n a l re s e a rc h specialist physicians’ attitude towards emergency medicine; a semi-structured qualitative study shahrooz tabrizi1, amir nejati1, saharnaz nedjat2, seyed mojtaba aghili1∗ 1. department of emergency medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. 2. department of epidemiology, school of public health, tehran university of medical sciences, tehran, iran. received: may 2017; accepted: december 2017; published online: 16 january 2018 abstract: introduction: the present study is a survey to assess the pros and cons of emergency medicine (em) from the viewpoint of the scholars from other medicine disciplines to improve the efficiency of em in the healthcare system. methods: this is a semi-structured qualitative study. face-to-face interviews with various physicians with different specialties were performed to gather information on their viewpoints. study population was selected mainly based on their history of collaboration with emergency medicine specialists in several educational hospitals in tehran, iran. all interviews were recorded and then transcribed to paper. data were mainly categorized and reported into four themes: 1) general aspects of emergency medicine, goals and policies 2) management of emergency department 3) educational aspects 4) therapeutic aspects. results: 22 specialist physicians with the mean age of 47.3±7.6 years were studied (77.3% male). the average of their work experience as a specialist was 13.6±7.5 years. from the viewpoint of other experts, the establishment of em and training of em specialists is accompanied with relative disadvantages and advantages regarding goals and policies, patient management, therapeutic interventions and student education in the emergency department. initiating resuscitation and maintaining hemodynamic stability and appropriate triage of the patients can add to the benefits of em by preventing unreasonable hospitalization, and reducing the workload and difficulty of the work of other professionals working in the hospital. conclusion: based on the results of the current study, it seems that most iranian specialist physicians have a positive attitude towards emergency medicine and think that emergency medicine could have beneficial effects for the health system and hospital management system. keywords: emergency medicine; emergency service, hospital; attitude of health personnel © copyright (2018) shahid beheshti university of medical sciences cite this article as: tabrizi sh, nejati a, nedjat sh, aghili seyed m. specialist physicians’ attitude towards emergency medicine; a semistructured qualitative study. emergency. 2017; 6(1): e6. 1. introduction l aunching a medical project in any region of the world is important due to its specific social, economic, and cultural requirements. in addition to its effects on the society, it specially affects other activists in the related field. now that over a decade has passed since emergency medicine (em) was launched in the iranian health system; it is an opportunity to explore its various aspects (1-3). considering the relatively new characteristics of em field in the iranian health care system, reviewing the opinion of other medical disciplines about em, may be useful for governmen∗corresponding author: seyed mojtaba aghili; department of emergency medicine, imam khomeini hospital, tehran university of medical sciences, tehran, iran. tel: +989124592479; email: m-aghili@tums.ac.ir tal health policy makers and could be referred for reasonable distribution of resources (4, 5). apparently, em is past its deployment stages in iran and has stepped into the stage of institutionalization, so it directly affects the society’s health, and its enforcement impact has been revealed (6-12). considering what was mentioned above, we decided to ask about the attitudes of other specialist physicians regarding this field of medicine. the present study is a survey to assess the pros and cons of em from the view point of the scholars from other medicine disciplines to improve the efficiency of em in the healthcare system. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. tabrizi et al. 2 2. methods 2.1. study design and setting this is a semi-structured study had been conducted as a qualitative research from 2014 until 2016 in tehran, iran. the study protocol was approved by emergency medicine department research council and ethics committee of tehran university of medical sciences. the researchers committed themselves to maintaining the principles of secrecy, and also did not any deliberate or unconscious censorship of the interviewees’ statements. they were ensured that data will be recorded and typed confidentially without the participants’ name and solely on the basis of an encoded data. 2.2. participants convenience sampling was carried out. study population included different faculties and specialists working in 3 educational hospitals affiliated to tehran university of medical sciences. the specialists who had the most contact with the emergency department were included. based on this decision, radiology, pathology, skin, radiotherapy and rehabilitation departments were excluded. also due to the decision for evaluation of adults in the surgical and internal parts of emergency department, gynecologists and pediatricians were also excluded from the study. the names of the departments of each hospital were written on separate papers, and placed inside three separate bags each representing one of the hospitals. then, three pieces of paper were drawn from each bag and samples were consecutively selected from the doctors practicing in the department the name of which was drawn. after that, by making an appointment and explaining the aim of the study, the eligible ones were asked to participate if they were interested. not willing to participate in the study was considered as exclusion criterion. sample selection was continued until data saturation was reached. 2.3. data gathering face-to-face interviews about 30-40 minutes long were held by the same interviewer in order to gather information. interviews were recorded. the research was done in line with the principles introduced in the declaration of helsinki regarding ethics. the interview method was semi-structured and open .they were asked to state their points of view about emergency medicine on the topics related to the goals of the current study. the interview was done purposefully and based on the following questions. • what are the benefits of emergency medicine? • what are the disadvantages of emergency medicine? • what is the importance of emergency medicine in the hospital? • what is your attitude and view on the specialty of emertable 1: frequency of specialties participating in the study (n=22) specialty n (%) internist 6 (27.3) general surgeon 5 (22.7) infectious disease specialist 4 (18.3) cardiologist 2 (9.2) gastroenterologist 1 (4.5) oncologist 1 (4.5) endocrinologist 1 (4.5) orthopedic surgeon 1 (4.5) neurologist 1 (4.5) gency medicine? • what role can an em specialist have in the emergency department? all interviews were recorded and then transcribed to paper. data were mainly categorized and reported in four themes: 1) general aspects of emergency medicine, goals and policies; 2) management of emergency department; 3) educational aspects of emergency medicine establishment; 4) therapeutic interventions conducted by emergency medicine physicians. each category was also divided into different sub-sections that will be explained separately in the results section. 2.4. statistical analysis data analysis was done using thematic content analysis based on krippendorff approach (data collection, data reduction, deduction, and analysis). to verify the accuracy of the data, member checking methods were used. to confirm the coding and increase the validity of the analysis, the text was given to the other two peers, as anonymous, and an understanding was reached regarding the concepts and the division of the categories. participants’ comments in the semistructured interviews were collected and recorded and then typed, coded and analyzed based on the krippendorff approach. 3. results 3.1. baseline characteristics of interviewees out of the 48 specialists who were asked to participate in the project, 22 (45.8%) were willing to participate and entered the study. these 22 specialist physicians had the mean age of 47.3±7.6 years and the average of their work experience as a specialist was 13.6±7.5 years (77.3% male). table 1 shows the frequency of specialties that participated in the study. 3.2. interviewees’ opinions: 3.2.1. general aspects of emergency medicine, goals and policies this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e6 3.2.1.1. advantages half of the respondents acknowledged the fact that it is undeniable that the field of emergency medicine is useful and necessary (54.5%). some professors who were interviewed stated that the presence of emergency medicine provides reassurance for other disciplines and reduces their stresses (18%). in addition, some interviewees emphasized that the presence of emergency medicine has reduced mortality rate and health care costs. 3.2.1.2. disadvantages some of the interviewees stated that emergency medicine physicians’ consecutive shifts can results in fatigue and increase the likelihood of medical errors (9%). one of the interviewees believed that there is no defined and targeted policy regarding the education and the duties of this specialty. some believed that because of the heavy duty and stresses of this specialty it is not suitable for female doctors (9%). 3.2.2. management of emergency department 3.2.2.1. overall management professors interviewed believed that the role of this discipline as the custodian of emergency department (ed) is undeniable and exclusive responsibility of critically ill patients should be given to emergency medicine specialists (18%). 3.2.2.2. admission another point emphasized by various interviewees was the necessity of taking into account the indications of admission despite the presence of different side pressures (18%). some participants believed that the responsibility of triage should be given to a doctor, not a nurse, so that management of the patients who are admitted could be done better (9%). the load of patients without an indication for admission to ed causes exhaustion of the nursing and lab staff and can consequently affect the treatment of patients who really need the emergency care. 3.2.2.3. disposition 3 of the respondents emphasized the need to stabilize an unstable patient before being transferred to other services (13.6%). another respondent also emphasized this point in some other way and stated that an unstable and high risk patient should not be transferred to the ward just because the ed is crowded. the interviewees believed that emergency medicine service has a unique role in disposition of the patients that other services refuse to admit them (13.6%). 3.2.2.4. interaction with other services almost half of those interviewed believed that greater coordination and interaction need to be established between various services and emergency service (45%). some have suggested that joint meetings between the services, common morning reports, joint protocols or common rounds in the emergency department could result in more coordination. five of the professors pointed to the time of the consultation with different services, they believed that the consultation should be done in a timely manner so that the admitting service could be involved in management of the patients (22%). 3.2.3. educational aspects of emergency medicine establishment 3.2.3.1. advantages interviewees believed that the continued presence of faculty members in the emergency department has a positive impact on treatment of patients (27%). additionally, some professors believed that the emergency department environment is suitable for practical and scientific education of students (9%). 3.2.3.2. disadvantages some professors who were interviewed believed that improving residency training in this field is required. also, some believed that the high load of admitted patients not only affects the training of emergency medicine residents but also residents in other disciplines. 3.2.4. therapeutic interventions conducted by emergency physicians 3.2.4.1. advantages a major part of the interviewees emphasized that specialized treatment in a minimum of time by em professionals improves emergency care provided for the patients in the emergency department. special emphasis was once again on the attendance of the faculty of emergency medicine and also it was noted that due to the comprehensive view of the em specialists the treatment of patients was associated with a significant improvement. 3.2.4.2. disadvantages four professors pointed to the prolonged duration of treatment for some patients in levels 3 and 4 of triage in emergency room that in some cases leads to doing unnecessary measurements (18%). some of those interviewed also stressed that due to the high false-positive results in some lab tests these unnecessary diagnostic tests should be avoided as much as possible. 4. discussion based on the results of the current study, it is likely that most iranian specialist physicians have a positive attitude towards emergency medicine and think that emergency medicine could have beneficial effects on the health care and hospital management systems. eds are usually overcrowded wards with unpredictable referrals. therefore, they need a different and special approach that leads to establishment of emergency medicine policies in hospitals (13-15). the interviewees suggest that many specialists in small towns can be replaced by em specialists due to the generalized curriculum and increased functional capabilities in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com sh. tabrizi et al. 4 this discipline. some authors believe that em and national health system interactions in some areas leading to development of policies for improving public health. existing literature also point to various problems that must be addressed in order to take full advantage of the existing and rapidly developing relations between em and public health. the clear policies by ministry of health regarding establishment of em in educational and non-educational hospitals would be valuable and influential (13, 16, 17). after launch of em, emergency department performance indices (edpi) were assessed in previous studies. it was reported that establishment of em was able to improve ed performance indices such as time to triage and patient disposition (18, 19). presence of em may affect the education of other medical disciplines and distance them from complicated and critical patients. to resolve this problem, simulation-based curriculum would have considerable benefits (20-23). one of the interviewees believed that the therapeutic scope of emergency medicine should be determined by other services to prevent potential challenges. apparently, preparing and approving a national curriculum, with respect to all other disciplines would be the sole solution in this regard (24, 25). the findings of this study showed that from the viewpoint of other experts working in the educational hospital, the establishment of em and training of em specialists is accompanied with relative disadvantages and advantages in goals and policies, patient management, therapeutic interventions and student education in the emergency department. initiating resuscitation and maintaining the hemodynamic stability and appropriate triage of the patients can add to the benefits of em regarding prevention of unreasonable hospitalization, and reduction of the workload and complexity of the work of other professionals working in the hospital. 5. limitation lack of cooperation and lack of clarity in the comments of the interviewed experts and colleagues, due to some professional restrictions, caused some executive problems, which we tried to reduce as much as possible by expressing the desired goals of the research. 6. conclusion taken together, considering the points cited by interviewees it can be concluded that the scholars from other disciplines are well aware of the importance of the field of emergency medicine and there are many positive comments about this discipline and they believe that presence of this field has resulted in better management of ed. however, there are some criticisms of this discipline and the better coordination of em with other services is called for. 7. appendix 7.1. acknowledgements we would like to thank all the faculties who participated in this study. 7.2. authors’ contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none declared. 7.4. conflict of interest none declared. references 1. alagappan k, holliman c. history of the development of international emergency medicine. emergency medicine clinics of north america. 2005;23(1):1-10. 2. sklar d, handel d, hoekstra j, baren j, zink b, hedges j. the future of emergency medicine: an evolutionary perspective. academic medicine: journal of the association of american medical colleges. 2010;85(3):490-5. 3. smith j, shokoohi h, holliman j. the search for common ground: developing emergency 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the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e34 rev i ew art i c l e applications of machine learning approaches in emergency medicine; a review article negin shafaf1, hamed malek1 ∗ 1. faculty of computer science and engineering, shahid beheshti university, tehran, iran. received: may 2019; accepted: june 2019; published online: 3 july 2019 abstract: using artificial intelligence and machine learning techniques in different medical fields, especially emergency medicine is rapidly growing. in this paper, studies conducted in the recent years on using artificial intelligence in emergency medicine have been collected and assessed. these studies belonged to three categories: prediction and detection of disease; prediction of need for admission, discharge and also mortality; and machine learning based triage systems. in each of these categories, the most important studies have been chosen and accuracy and results of the algorithms have been briefly evaluated by mentioning machine learning techniques and used datasets. keywords: artificial intelligence; machine learning; emergency medicine; emergency service, hospital; triage cite this article as: shafaf n, malek h. applications of machine learning approaches in emergency medicine; a review article. arch acad emerg mede. 2019; 7(1): e34. 1. introduction a rtificial intelligence has been used in different health and medical fields. in particular, different artificial intelligence and machine learning techniques have attracted attention in the recent years. emergency department (ed) and triage are among the most important parts of any hospital in which diagnostic and therapeutic interventions should be performed both rapidly and effectively. as the number of people referring to ed increases, common traditional techniques may not be sufficient. thus, different methods of artificial intelligence such as natural language processing, data mining, clustering and classification algorithms should be used to significantly enhance the efficacy of hospital emergency system. using artificial intelligence will bring some advantages; it will reduce human errors as well as time and expenses and improve the pace of providing services. moreover, machine learning techniques usually have a comparable and even better accuracy compared with medical staff of the hospital. several studies have assessed application of artificial intelligence in ed triage from different points of view. though, most of them can be divided into three categories, which will be further discussed in detail. ∗corresponding author: hamed malek; shahid beheshti university, shahid shahriari square, daneshjou boulevard, shahid chamran highway, tehran, iran. email: h_malek@sbu.ac.ir phone/fax: +98 (21) 29904106 machine learning systems have the potential of prediction and early detection of diseases in ed so that the disease can be treated more effectively and disease progression and occurrence of inappropriate complications can be prevented. this issue is discussed in detail in part 3.1 by reviewing the most important studies in this regard. increase of the number of patients referring to ed will result in overcrowding, which decreases the efficiency of medical staff and increases the delay for patient visit. consequently, artificial intelligence and machine learning techniques can be used in order to manage the ed, allocate money and equipment, and discharge patients more properly. a series of studies are provided in part 3.2 in this regard, in which admission of patients referring to ed, their discharge or mortality is predicated. in part 3.3, studies on electronic triage methods based on machine learning techniques have been briefly reviewed. studies presented in this part, prioritize patients based on different machine learning techniques, which is usually both faster and more accurate compared with traditional methods and emergency severity index (esi) (1). faster triage not only improves patient satisfaction, but also improves performance of ed and prevents its overcrowding. 2. machine learning techniques and its different types machine learning is an important subset of artificial intelligence, which enables machines to learn and act on specific this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shafaf et al. 2 table 1: different models on disease prediction disease algorithm result year aki boosted ensembles of decision trees auc :0.720.87 2018 (8) logistic regression auc: 0.77 2018 (9) gradient boosting machine auc:0.73-0.97 2018 (12) deep learning accuracy: 99.1% 2018 (13) logistic regression auc : 0.74 2016 (10) binary logistic regression sensitivity :96.6% 2008 (11) specificity: 95.7% influenza bayesian classifier (naive bayes) auc: 0.92-0.93 2015 (15) bayesian network classifiers auc: 0.79 2014 (14) sepsis gradient tree boosting auc: 0.87-0.92 2018 (18) support vector machine auc: 0.86 2017 (19) copd and asthma random forest c-statistic: 0.84 2018 (20) logistic regression accuracy: 89.1% 2017 (21) naive bayes accuracy: 70.7% 2013 (23) tree-based decision model auc: 0.83 2010 (22) uti extreme gradient boosting auc: 0.90 2018 (17) appendicitis rule base ap: 0.86 2013 (25) aki: acute kidney injury; copd: chronic obstructive pulmonary disease; uti: urinary tract infection; ap: average precision and recall. tasks. in fact, machine learning consists of a set of techniques and algorithms which can predict some future events or classify some data by learning the patterns in the existing data. some of the most important algorithms in this field are logistic regression, support vector machines (svm), naive bayes algorithm (2), decision trees, random forest, gradient boosting and deep learning. logistic regression is a machine learning algorithm, which tries to find a linear model of the relations between variables by fitting a line on the curve of the given data (3). it can also be used for classification purposes. one of the frequently used algorithms for data classification is svm algorithm (4). it has been proven to find the best data classifier for the given data. svm can achieve a very good generalization performance. decision tree is another tool for modeling data, which uses tree-like structures for classifying the decisions in order to output the class of the given data. when a number of decision trees are employed, an ensemble learning method called random forest is produced (5). gradient boosting method is also widely used in some machine learning problems (6). it produces an ensemble model of the data by employing some weak models. one of the advantages of this method is its ability to reduce bias and variance in the model. deep learning is another algorithm, which has recently been widely recognized as a successful method in some complex machine learning tasks (7). deep learning is a part of another class of machine learning methods named artificial neural network (ann). in ann algorithms, a network of cells is produced and the connections between the cells are adjusted in a way that the resulting network can learn the structure of the training data. in deep learning, the number of layers in the network is much higher than an ordinary ann. this enables the algorithm to extract higher level features from the input data. 3. review of studies in the following sections, the three most important issues in ed, including prediction and detection of disease; prediction of need to admission, discharge, and also mortality; and electronic triage will be discussed separately by reviewing the most important articles. 3.1. disease prediction and detection a lot of information about patient’s demographic characteristics, symptoms, and disease appearance is available in eds through electronic health record (ehr), nursing reports, laboratory test results and patient profiles. this information could be used by machine learning techniques in order to predict and detect different diseases so that medical interventions take place more rapidly and effectively. some of the most important diseases, which can be detected through machine learning techniques, are presented below (table 1). acute kidney injury acute kidney injury (aki) is a disease that can occur in a few hours to a few days and can lead to kidney failure if not managed properly and the patients would need dialysis for the rest of their lives and they may even die due to kidney failure. however, if this disease is diagnosed soon, it can be rapidly controlled to avoid complications. artificial intelligence and machine learning techniques can help in fulfilling this objective. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e34 in 2018, a method was proposed, which was based on boosted ensemble of decision trees which was able to detect aki at time of onset, as well as 12, 24, 48, and 72 hours before the onset of the disease (8). in this study, two databases were used, both of which contained information of patients above 18 years old. stanford medical center dataset contains information of patients in all hospital wards and beth israel deaconess medical center contains information of patients in icu ward collected from mimic-iii database, which is available. efficiency of this algorithm was compared with sequential organ failure assessment (sofa) method. according to area under the curve (auc), the accuracy of this method in prediction of aki at the time of onset is 87%. additionally, the accuracy of this method for 12, 24, 48, and 72 hours before onset of aki is 80%, 79%, 76%, and 72%, respectively. another study assessed clinical notes in the first 24 hours after admission in intensive care unit (icu), which is extracted from mimic-iii dataset (9). by means of natural language processing, meaningful words and representations of concept and embedding were produced and different supervised classifiers such as multinomial naive bayes (mnb), l1-/l2regularization, svm, logistic regression (lr), random forest (rf), gradient boosting and decision tree (gbdt) and architecture knowledge-guided deep learning were used to design the model. among these, the highest accuracy belonged to lr with 77.90%. in one other study in this regard, a model for prediction and detection of aki in patients above 60 years old was proposed in which collected information of 25521 patients during one year was utilized (10). in this study, five machine learning techniques, including logistic regression, support vector machines, decision trees, naive bayes and ensemble were used for disease prediction and detection. these methods were compared with each other and based on auc; logistic regression was the most accurate method for disease detection with 74% accuracy; while ensemble method was the most accurate for disease prediction with 66% accuracy 24 hours before the onset of the disease. aki is a major complication with a very high reported mortality rate for people trapped beneath the rubble following earthquakes. in these cases, aki can be prevented through rapid and early fluid therapy. this issue is evaluated in a study, which presents two algorithms to help medical staff predict aki on the first day after a disaster (11). this method is based on biochemical parameters and can be utilized very easily even in disasters. early prophylactic hydration therapy for patients with kidney disease, who are susceptible to aki, can reduce its occurrence during natural disasters. since in these situations, a huge resource for fluid therapy might not be available, it is vital to separate those who are at risk of aki from those who are not at risk. for this purpose, decision rules were designed by considering receiver operating characteristic curve and binary logistic regression, which have a sensitivity of 96.6% and specificity of 95.7% for aki prediction. there was another method for aki risk predication in patients admitted in hospitals. data of patients were extracted from electronic health record of academic medical centers from 2008 to 2016. using gradient boosting machine, aki can be predicted with auc of 0.73 to 0.97 in different conditions (12). deep learning method was deployed in a study on prediction of aki in icu ward. this study was conducted on mimic-iii database and was able to predict aki with 99.1% accuracy (13). influenza influenza is an infectious disease affecting many people every year and it can cause epidemics due to its contagious nature. thus, early diagnosis and prediction of influenza can prevent its epidemics and save people’s lives, reduce treatment costs and lessen patient reference to ed. a study in this regard has proposed an automatic method for influenza diagnosis based on ehr in which symptom extraction, feature selection, and their classification for influenza diagnosis have been performed systematically (14). in fact, natural language processing and different classifiers have been used in a combined manner so that influenza disease can be diagnosed automatically based on ehrs. more accurately, we can state that in this method, free-text reports of ed are processed using different language processing parsers such as topaz, medlee, and an expert to extract the important information about influenza. then bayesian network classifier uses expert-defined-bn, bn-emtopaz, or bn-em-medlee for estimation of influenza probability. finally, for evaluation of this method, 9 experiments were conducted on three parsers and three classifiers and the results were compared with gold standard. highest accuracy was achieved when an expert processed the reports and extracted influenza related information and bn-emtopaz classifiers were used, auc of which was 0.79 and showed the highest value among the 9 experiments. free-text reports in ed can be helpful in early and real-time diagnosis of influenza. in a study, it is reported that influenza is diagnosed in eds using machine learning techniques based on these reports (15). the data used in this study included 31268 ed reports of 4 hospitals from 2008 to 2011. then, by means of topaz, a natural language processing tool, features and terms related to influenza were extracted form reports and codified into three categories (acute, non-acute, and missing). then, 7 classifiers including naive bayes, bayesian network with the k2 algorithm, efficient bayesian multivariate classification, artificial neural networks, logistic regression, svm, and random forests were applied and the results were compared with each other. if there were missed data, bayesian (naive base) showed betthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shafaf et al. 4 ter performance with auc of about 92-93%. according to studies conducted to compare different methods of natural language processing in influenza diagnosis, it can be concluded that by using all clinical notes, influenza can be diagnosed with 92.9% accuracy, while when only symptoms reported by the patient is processed, the accuracy of these methods drops to 70.3% (16). urinary tract infection (uti) urinary tract infection is a common disease in eds with a high rate of diagnostic error, since urine culture is not available until 24 to 48 hours after the first visit. diagnosis and decision making on medication prescription is based on symptoms, physical examination findings, and results of laboratory tests, which can cause overuse of antibiotics and resistance against antibiotics. previous studies have shown that diagnostic efficacies of laboratory tests and individual predictions are not enough. a study performed in this regard has proposed some models for prediction of uti based on machine learning for different patients in ed (17). data used in this study was collected from clinical reports of health profiles of patients above 18 years old admitted to 4 eds between 2013 and 2016. proposed models for disease prediction used 7 machine learning algorithms including random forest, extreme gradient boosting, adaptive boosting, elastic net, support vector machine, logistic regression, and neural network. results of this study showed that among the mentioned algorithms, xgboot algorithm provided the best efficacy with auc of 0.90. sepsis sepsis is a severe infection with a high mortality rate and high therapeutic costs. consequently, early diagnosis and treatment of sepsis can reduce mortality rate among the patients and reduce therapeutic costs for these patients. a machine learning based method has been proposed for prediction and diagnosis of sepsis, which can improve the treatment procedure of patients (18). using gradient tree boosting algorithm, three levels of sepsis are detected. features used in this method include values of 6 vital signs in eds, general wards, and icu and eventually, area under the roc value for sepsis and severe sepsis are 0.92 and 0.87, respectively. another study suggests an automatic system by using machine learning techniques for triage of sepsis patients in ed (19). in this study, a dataset including patient’s information and data including ed triage report note, triage vital signs, and icd-9-cm codes was extracted from ehr. according to the reported results, it can be concluded that using free-text data from ed triage, as well as structured data such as vital signs and statistical information can significantly improve detection of patients suspected to infection. two models, bag of words model and topic model were used for representation of free-text data and then an svm was used to design the predictor model. applying svm of bag of words is more effective compared with other methods and auc value for test and train data are 0.86 and 0.89, respectively. chronic obstructive pulmonary disease (copd) and asthma patients with chronic obstructive pulmonary disease and asthma, face the risk of exacerbation of their disease every day. using special tools when necessary, the probability of exacerbation of the disease can be effectively reduced. by means of machine learning techniques, some methods have been proposed, which can be used for early diagnosis of exacerbation of the disease. asthma condition and copd exacerbation in eds have been assessed in different studies using different machine learning methods such as lasso regression, random forest, and boosting, and deep neural network, and some models have been developed based on available data. these methods were compared based on c-statistic index, which showed that random forest method has the highest efficacy with 84% accuracy (20). in another proposed algorithm, some features are determined by physicians for both prediction of patient’s triage and diagnosis of disease exacerbation and data are labeled. then, the algorithm is trained by different methods. according to the obtained result for different classifiers of machine learning, gradient-boosted decision tree and logistic regression had the highest efficacy with an accuracy of 88.1% and 89.1%, respectively (21). another study predicts the severity of asthma exacerbation among children in ed of eastern ontario pediatrics hospital. data of children aged 1 to 17 years were used and a tree-based decision model was designed for prediction of severity of asthma exacerbation with auc of 0.83 (22). moreover, other machine learning methods have been used to predict this disease. in one of these studies, five different models were designed in this regard and naive bayes model was the most efficient model with 70.7% accuracy. therefore, this can be used as a complementary model along with the traditional models such as pediatric respiratory assessment measure (pram) score (23). appendicitis appendicitis is one of the most common causes of abdominal pain in patients referring to ed. a major challenge in diagnosis of appendicitis is wrong diagnosis or delayed diagnosis and perforation. thus, early and accurate diagnosis of appendicitis is necessary (24). an automatic system has been designed in which major components are extracted from clinical notes in eds and laborathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e34 table 2: different models for prediction of disposition prediction algorithm result year need for admission xgboost auc: 0.92 2018(29) need for admission gradient boosted machines auc:0.85 2018 (30) icu readmission gradient boosted machine auc: 0.76 2018 (33) in-hospital mortality lstm auc: 0.94 2018 (37) length of icu stay logistic regression auc :0.93 2018 (37) readmission random forest auc: 0.58 2018 (37) need for admission naive bayes+ logistic regression auc: 91.0 2017 (28) need for admission nu-support vector machine f-score:0.77 2017 (36) in-hospital mortality random forest auc: 0.86 2016 (34) length of stay logistic regression random forest > clinicians 2015 (35) need for admission logistic regression auc: 0.800.89 2013 (32) need for admission logistic regression specificity=96.8% 2011 (31) sensitivity=33.4% icu: intensive care unit, lstm: long short-term memory. tory test results. in this model, risk of appendicitis in children is classified to high risk, low risk, and equivocal (25). this method is based on machine learning techniques and natural language processing in both of which structured information derived from ehrs (laboratory results) and clinical notes of ed are used. firstly, the information about risk of appendicitis is extracted using natural language processing techniques. then, a rule based method was used to classify appendicitis risk to three classes (high risk, low risk, and equivocal). finally, efficacy of this method was compared with gold standard method, which is designed manually by physicians. mean precision and recall of this system were 38% and 86%, respectively. electronic surveillance systems can detect the disease faster than diagnosis based systems based on chief complaint of patients. in this regard, a classifier is designed to collect free-text reports about chief complaint of patients in triage to classify patients in one of the 7 following categories: respiratory, botulinic, gastrointestinal, neurologic, rash, constitutional, and hemorrhagic syndromes (26). final result of the study shows that for most of these syndromes, classification systems can detect nearly half of patients with a specificity more than 90% and positive predictive value of 12 to 44 percent, predicting the related syndrome with an overall accuracy of 92.3% to 99.1% for these 7 syndromes. 3.2. prediction of disposition and mortality considering the increasing requests, boarding of patients admitted to ed is an issue due to the overcrowding. prediction of discharge and admission of patients can be performed automatically to improve this process. to achieve this goal, supervised machine learning methods and available health data are used to help in admission of new patients. early prediction of admission can speed up allocation of resources and bed to the patient and shorten the boarding times. on the other hand, according to the results, it has been proved that in some cases, nurses are not sure when predicting patient admission and show lower performance compared with machine learning methods (27). thus, machine learning methods can be time-saving and improve outcomes in medical interventions and patient satisfaction, and reduce hospital costs. different models have been proposed for early predicting of patient admission (table 2). in a study in this regard, a model was designed based on combined generative-discriminative approach (28). number of variables has been reduced by means of naive bayes (generative) and then a regression model (discriminative) is applied on the results of the previous model. using data of available ehrs, this model can predict 73.4% of admissions with a specificity of 90% and 35.4% of admissions with a specificity of 99.5% (auc=91%) in the first 30 minutes. another study suggests a model based on machine learning in which, history of patients is used as well as the information collected in ed triage to predict patient admission or discharge (29). three binary classifiers, logistic regression, gradient boosting (xgboost), and deep neural networks, are applied on three kinds of datasets (first dataset only contains patient history, second dataset only contains triage information, and third dataset includes both patient history and triage information). results show that using patient history in addition to triage information significantly improves efficacy of the prediction and xgboost classifier provides the best efficacy with auc of 0.92. in another study, available methods in data mining were applied on electronic system data to form a prediction model for patient admission in ed triage (30). in this study, three algorithms including logistic regression, decision trees, and gradient boosted machines (gbm) have been used and results proved that gbm method provides the best perforthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. shafaf et al. 6 mance with auc of 0.85 and accuracy of 80.31% compared with the other two methods. yet, when it comes to interpretability of the data, adopting logistic regression model is a better choice. many models developed for prediction of hospital admission in eds are focused on a special group of patients or patients with special diseases and just a few studies have discussed admission of all patients. a study suggests a model to predict risk level at the time of admission. in this model, data of all patients with any disease in triage is assessed and data collected from the routine examinations performed at the time of triage is used (31). this model helps nurses in triage to make faster decisions regarding whether the patient should be admitted or not, so that resources are allocated to those who should be admitted and ed crowding is reduced. logistic regression is used to develop this method with a specificity of 96.8% and sensitivity of 33.4%. additionally, result of a study showed that logistic regression method with auc of 0.80 to 0.89 can be generalized to different hospitals with different number of patients (32). in some cases, patients are transferred from icu to general ward and then they are transferred to icu which can cause problems such as longer icu stay and increased costs. also, it can increase mortality rate. this issue is discussed in a study and icu readmission was predicted by machine learning techniques using data of ehrs (33). gradient boosted machine is used to design this model and the results are compared with two decision rules stability and workload index for transfer (swift) score and modified early warning score (mews). it can be concluded from reported results that the proposed method with auc of 0.76 is significantly better than mews method with auc of 0.65 and swift method with auc of 0.58. machine learning methods can also be helpful in prediction of patient mortality. analyses and predictions performed in ed are often limited to clinical decision rules (cdrs), which use simple heuristics and scoring systems. a major problem of cdrs is that they are not generalizable and cannot be updated using new data. but, new techniques are based on machine learning and can use many variables from ehrs. mortality of patients with sepsis in ed is predicted using a machine learning based method (34). a random forest model was developed using data of ehrs and was compared with models developed based on regression tree (cart) and logistic regression models, where it showed better efficacy with auc of 0.86. moreover, machine learning approach can better predict mortality rate of patients with sepsis compared with available cdrs and traditional data analysis techniques. also, machine learning can be used to predict hospital length of stay so that patients can be prioritized for discharge. logistic regression and random forest method have been used in a study (35). comparison of these methods with prediction of hospital staff revealed that both methods have higher sensitivity and lower specificity. several other studies have been conducted in prediction of admission or discharge of patients using different machine learning techniques. in one of these studies, prediction is performed by text mining of clinical reports by applying different algorithms. comparison of these methods showed that, nu-support vector machine provides the best performance with f1 score of about 0.77 in comparison to other algorithms (36). another study has evaluated patient admission, in hospital patient mortality, and length of stay on mimic-iii database, separately. different classic machine learning methods such as svm, lr, mlp, random forest, and gradient boost classifier and sequential models such as lstm and cnn-lstm have been used and the results are compared (37). in terms of patient mortality prediction, among classic models, mlp method with auc of 0.85 and among sequential models, lstm model with auc of 0.94 showed the highest accuracies. in terms of length of stay prediction, among classic models, logistic regression method with auc of 0.93 and among sequential models, lstm model with auc of 0.88 provided the best efficacies. finally, in terms of patient admission, random forest and lstm models had provided the best results with auc of 0.58. 3.3. machine learning based triage systems since eds are overcrowded, the main problem in triage is to classify patients based on disease severity with a fast and accurate method to provide best services. using machine learning techniques can improve pace and efficacy of patient management in triage compared with traditional methods. studies performed in recent years are discussed in the following paragraphs (table 3). recently, a study has been conducted to suggest a method for proper classification of patients in triage into 5 groups based on disease severity (38). a new algorithm, namely randomly occurring distributed delayed particle swarm optimization (roddpso), is proposed in this study, which is based on pso evolutionary algorithms and is a method for clustering ed data suggested for patient classification. efficacy of this method was finally evaluated based on mean silhouette value with two clustering algorithms k-means and fcm. reported results showed that roddpso with a value of 0.31 for the mentioned index has a higher efficacy compared with the other two methods. instead of using traditional protocols in triage, which are mostly based on disease symptoms, clinical decision support systems (cdsss) may be used. cdsss have been evaluated in a study for triage assistance using machine learning algorithms, which directly learn the model form data instead of an expert (39). there are different approaches for designing a model and the method should be chosen in a way that the result can be interpreted by physithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e34 table 3: different models used in machine learning based triage systems algorithm result year decision tree accuracy=84.0% 2018 (41) support vector machine accuracy=84.0% random forest auc: 0.73-0.92 2018 (40) roddpso mean silhouette value: 0.31 2018 (38) naive bayes classifier accuracy: 87.9% 2008 (39) bayesian network accuracy:86.9% roddpso: randomly occurring distributed delayed particle optimization. cians. for instance, decision trees and bayesian networks are appropriate methods. furthermore, types of information used to develop the model are also important. expert opinion or data can be used as information resources. studies suggest that using data and machine learning methods acts better compare with expert opinion in models. also, bayesian networks are more interpretable compared with rule-based models such as decision tree. thus, developing models based on these methods can provide higher accuracy compared with other models. bayesian network algorithms achieved accuracy of 87.9% and 86.9% by using naive bayes classifier and k2 algorithm, respectively, which are much higher compared with decision tree method. usually, standards of ed triage mostly depend on individual diagnosis and they have limited ability in identifying high risk patients. a method of assessment based on electronic triage using machine learning techniques is proposed in a study, which can predict high risk patient and separates patients properly (40). to be more accurate, this study classifies esi level 3 patients so that prediction results can be more easily analyzed in triage. in this study, three decision tree learning models or in other words, random forest is used to predict intensive care, emergency procedure, and hospital admission for ed patients. finally, the output of this model for each patient is one of these three categories. results of this prediction has an auc ranging from 0.73 to 0.92. this method classifies esi level 3 patients more accurately. another study on electronic triage of ed patients has proposed models with supervised machine learning algorithms and compared them (41). classifiers such as naive bayes, support vector machine, decision tree, and neural network have been deployed, among which support vector machine and decision tree provided highest efficacy with an accuracy of 84%. another study proposed a calculative algorithm using fuzzy logic and decision tree to classify patients in ed triage (42). 4. conclusion abilities of artificial intelligence and machine learning techniques can be used in medicine, especially in emergency medicine and in some important issues including disease prediction, admission or discharge prediction, and patient triage. by early prediction and diagnosis of high risk diseases such as aki, sepsis, pneumonia, and contagious diseases such as influenza, necessary interventions can be performed more rapidly in ed to prevent multiple disease progression complications. in this regard, different machine learning algorithms such as logistic regression, bayesian network, deep learning etc. have been deployed, which generally have shown high accuracy ranging from 70% to 90%. additionally, these algorithms and other methods can be helpful in prediction of patient admission and improve patient triage. 5. appendix 5.1. acknowledgements none. 5.2. authors contributions negin shafaf and hamed malek designed the study, developed the methodology, collected the data, performed the analysis, and wrote the manuscript. both authors reviewed the final manuscript. 5.3. funding support none. 5.4. conflict of interest the authors have no conflict of interest to declare. references 1. stewart j, sprivulis p, dwivedi g. artificial intelligence and machine learning in emergency medicine. emergency medicine australasia. 2018;30(6):870-4. 2. bonaccorso g. machine learning algorithms: packt publishing ltd; 2017. 3. kleinbaum dg, dietz k, gail m, klein m, klein 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2017;100:1-8. 37. tang f, xiao c, wang f, zhou j. predictive modeling in urgent care: a comparative study of machine learning approaches. jamia open. 2018;1(1):87-98. 38. liu w, wang z, liu x, zeng n, bell d. a novel particle swarm optimization approach for patient clustering from emergency departments. ieee transactions on evolutionary computation. 2018. 39. abad-grau mm, ierache j, cervino c, sebastiani p. evolution and challenges in the design of computational systems for triage assistance. journal of biomedical informatics. 2008;41(3):432-41. 40. levin s, toerper m, hamrock e, hinson js, barnes s, gardner h, et al. machine-learning-based electronic triage more accurately differentiates patients with respect to clinical outcomes compared with the emergency severity index. annals of emergency medicine. 2018;71(5):565-74. e2. 41. olivia d, nayak a, balachandra m, editors. machine learning based electronic triage for emergency department. international conference on applications and techniques in information security; 2018: springer. 42. mondragon n, istrate d, wegrzyn-wolska k, garcia jc, sanchez jc. patient classification algorithm at urgency care area of a hospital based on the triage system. journal of medical informatics & technologies. 2013;22. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction machine learning techniques and its different types review of studies conclusion appendix references daily situation report on coronavirus disease (covid-19) in iran march 15, 2020 national committee on covid-19 epidemiology ministry of health and medical education, ir iran total lab-confirmed cases 13,938 total associated deaths 724 total recovered cases 4,590 new cases 1,209 top 3 provinces based on recovery rate*  markazi (1st)  semnan (2nd)  kordestan (3rd) age groups with highest recovery rate*  40-49 years (1st)  30-40 years (2nd) deaths recovered age (year) 65.5 51 mean 67 50 median 3 < 1 minimum 97 91 maximum gender 59% 58% male 41% 42% female based on available data, we considered patients with death outcome, as well as those admitted to icu or under mechanical ventilation as more severe cases. the information in this chart is based on hospitalized cases, and outpatients are not included in this calculation. inclusion of outpatients and asymptomatic cases would decrease the proportion of severe-to-mild cases. the way recovered cases referred to the hospital percent* ambulance 12.5 outpatient visit 87.5 hospital ward critical care units 6 general 94 respiratory distress 8 low gcs 2 the above table shows that about 12% of recovered cases initially needed to be transferred to the hospital by ambulance, and so, probably had relatively severe disease. it is hoped that the severity of the primary symptoms may not necessarily mean a poor prognosis in all cases in iran. in fact, despite severe initial symptoms, there may be the chance for recovery. it should be acknowledged that some of the hospital transferred by ambulance might be due to panic attack associated with the onset of the covid-19 symptoms. while this proportion might be negligible, it is believed that stress and anxiety itself can compromise immune system and result in poor prognosis. the chance of recovery seems quite low for those with low gcs. § the values presented here does not intend to be used for causal inference, so, none of them are adjusted for potential confounders. *recovery rate: total recovered/total lab-confirmed cases; icu: intensive care unit. gcs: glasgow coma scale source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1,000 1,500 1 9 -f e b 2 0 -f e b 2 1 -f e b 2 2 -f e b 2 3 -f e b 2 4 -f e b 2 5 -f e b 2 6 -f e b 2 7 -f e b 2 8 -f e b 2 9 -f e b 1 -m a r 2 -m a r 3 -m a r 4 -m a r 5 -m a r 6 -m a r 7 -m a r 8 -m a r 9 -m a r 1 0 -m a r 1 1 -m a r 1 2 -m a r 1 3 -m a r 1 4 -m a r n u m b e r confirmed cases and associated deaths confirmed cases associated deaths severe, 13.7 mild, 86.3 proportion of more severe forms of the disease to total confirmed cases emergency. 2018; 6 (1): e19 or i g i n a l re s e a rc h emergency medicine resident versus radiologist in detecting the ultrasonographic signs of acute cholecystitis; a diagnostic accuracy study javad tootian tourghabe1, hamid reza arabikhan2, ali alamdaran3, hamid zamani moghadam2∗ 1. emergency department, hasheminajad hospital, mashhad university of medical sciences, mashhad, iran. 2. emergency department, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 3. radiology department, imam reza hospital, mashhad university of medical sciences, mashhad, iran. received: february 2018; accepted: march 2018; published online: 15 march 2018 abstract: introduction: dependence of ultrasonography on the operator’s skill plays a major role in the differences between various studies in reporting its diagnostic accuracy. therefore, the present study was done with the aim of comparing the ultrasonography findings performed by emergency medicine resident and radiologist in evaluation of acute cholecystitis. methods: the present diagnostic accuracy study has been carried out on patients presenting to the emergency department with complaint of pain in the right upper quadrant of abdomen suspected with acute cholecystitis. all the patients underwent gallbladder ultrasonography by a trained emergency medicine resident and a radiologist and their findings were compared with surgical and pathology findings regarding gallstone and increased gallbladder wall thickness. results: 51 patients with the mean age of 42.3±15.8 (17-81) years were analyzed (82.4% female). the overall agreement between emergency medicine resident and radiologist in ultrasonographic diagnosis of cholecystitis was 0.421 (95% ci: 0.118-0.724). based on the pathology and surgical findings, acute cholecystitis was confirmed for all 51 (100%) patients. meanwhile, based on the ultrasonographic report of radiologist and emergency medicine resident only 45 (88.2%) and 34 (66.7%) patients, respectively, were diagnosed with cholecystitis. screening performance characteristics of ultrasonography by radiologist for detection of gallbladder stone (p = 0.010) and gallbladder wall thickness (p < 0.0001) were significantly better than emergency medicine resident. conclusion: the screening performance characteristics of ultrasonography by radiologist in detection of gallstones and increased wall thickness of gallbladder were significantly better. keywords: gallstones; cholecystitis, acute; diagnostic imaging; ultrasonography © copyright (2018) shahid beheshti university of medical sciences cite this article as: tootian tourghabe j, arabikhan h, alamdaran a, zamani moghadam h. emergency medicine resident versus radiologist in detecting the ultrasonographic signs of acute cholecystitis; a diagnostic accuracy study. emergency. 2018; 6(1): e19. 1. introduction o ne of the most common causes of patients presenting to the emergency department with complaint of abdominal pain is acute cholecystitis. acute cholecystitis, which is an inflammatory disease of the gallbladder, is mostly due to presence of a stone, ischemia, movement disorders in gallbladder and biliary tracts, and obstruction ∗corresponding author: h zamani moghadam; emergency department, imam reza hospital, bahar avenue, mashhad, iran. tel: 09155811238 email: zamanimh@mums.ac.ir of the tracts by a tumor. statistics have indicated that 3% to 10% of the patients presenting to emergency department with complaint of abdominal pain are affected with acute cholecystitis (1-3). along with physical examination and laboratory evaluation, ultrasonography is usually considered the first diagnostic step for patients with suspected acute cholecystitis in the emergency department. availability, low cost and noninvasiveness of this imaging technique has made it the most commonly used diagnostic method in the emergency department (4-8). however, dependence of ultrasonography on the operator’s skill plays a major role in the differences between various this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com j. tootian tourghabe et al. 2 studies in reporting its diagnostic accuracy. for example, sensitivity and specificity reported for ultrasonography performed by emergency medicine specialist in detection of acute cholecystitis have been reported to be 83%, and 82%, respectively; while, these rates have been 87% and 86%, respectively, for radiologist (9). however, other studies show contradicting results and a sensitivity of 90% to 96% has been estimated for ultrasonography performed by emergency physicians (10, 11). these contradictions in opinion have resulted in inability to accurately decide regarding the diagnostic accuracy of ultrasonography in detection of acute cholecystitis. the present study aims to compare the ultrasonography findings performed by emergency medicine resident and radiologist in evaluation of acute cholecystitis. 2. methods 2.1. study design and setting the present diagnostic accuracy study has been carried out on patients presenting to the emergency department of imam reza hospital, mashhad, iran, between november 2015 and january 2017 with complaint of abdominal pain suspected with acute cholecystitis. all the patients underwent gallbladder ultrasonography by an emergency medicine resident and a radiologist and their findings were compared with surgical and pathology findings. protocol of this study was evaluated in the ethics committee of mashhad university of medical sciences and registered under the code ir.mums.fm.rec.1395.597. before being included in the study, informed consent was obtained from the patients or their relatives and the researchers adhered to the principles of helsinki declaration throughout the study period. 2.2. participants patients with acute pain in the right upper quadrant of their abdomen suspected with acute cholecystitis who would finally undergo surgery and the results of their gallbladder pathology was available were included in the study. exclusion criteria consisted of the patient not cooperating and not giving consent for performance of ultrasonography and the results of pathology of the patients not being available. no age or sex limitation was applied in the present study. 2.3. procedure in this study, ultrasonography of the right upper quadrant of the abdomen was performed by an emergency medicine resident and a radiologist independently and separately. ultrasonography was performed using an hs-2100 model portable ultrasonography device (honda company, japan) using a linear probe with a frequency of 5 to 7mhz. after the initial examination, the emergency medicine resident would perform ultrasonography and then the radiologist would repeat this diagnostic modality for the patients using the same ultrasonography device. ultrasonographic diagnosis of acute cholecystitis was based on the presence of at least one of the following symptoms in ultrasonography: impacted stone in cystic duct of gallbladder neck, sonographic murphy’s sign, thickening of gallbladder wall>3 mm, peri-cholecystic fluid collection the emergency medicine residents participating in the present study had attended theoretical and practical training courses of ultrasonography performance on patient’s bedside for diagnosis of acute cholecystitis. the decision regarding performing surgery on the patients or not was made by the surgeon in charge of the patient and based on a combination of clinical, laboratory, and ultrasonography findings. the gold standard in the present study was considered surgical and pathology findings of the gallbladder. 2.4. data gathering a senior emergency medicine resident was in charge of gathering patients’ data. the shifts in which this resident was present in the emergency department were planned randomly. to gather data, a pre-designed checklist including demographic data (age, sex), ultrasonographic findings of acute cholecystitis by an emergency medicine resident and a radiologist separately, and findings of gallbladder surgery and pathology was used. 2.5. statistical analysis considering 95% confidence interval (ci), 90% sensitivity of ultrasonography performed by and emergency medicine specialist, 30% prevalence, and 0.1 error, the minimum required sample size for his study was estimated as 42 patients and by considering missing 15% of the samples, in the end sample size was considered 50 patients (11). data were analyzed using stata 14.0 statistical software. results were expressed as frequency and percentage or mean and standard deviation. agreement rate of ultrasonography performed by emergency medicine resident and radiologist was reported by calculating kappa coefficient with 95% ci. then the true positive, true negative, false positive and false negative results reported by emergency medicine resident and radiologist regarding gallstone and gallbladder wall thickness were calculated by considering the results of surgery and pathology as the standard test. to compare the screening performance characteristics of ultrasonography by radiologist and emergency medicine resident fisher’s exact test was used. consequently, using vassarstats medical calculator, screening performance characteristics of gallbladder ultrasonography in detection of stone and gallbladder wall thickness were calculated. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e19 table 1: ultrasonographic findings of gallbladder by emergency medicine (em) resident and radiologist and their agreement rate with 95% confidence interval (ci) ultrasonographic finding em resident radiologist agreement (95% ci) > 3mm thickness 31 (60.8) 42 (82.4) 0.499 (0.271-0.725) sonographic murphy’s sign 27 (52.9) 19 (37.3) 0.691 (0.5030.877) gallstone 14 (27.5) 36 (70.6) 0.272 (0.1150.429) pericholecystic fluid 2 (3.9) 6 (11.8) 0.469 (0.045-0.892) data are shown as frequency (%). table 2: screening performance characteristics of ultrasound performed by radiologist and emergency physician in detection of gallstone characteristics radiologist emergency physician true positive 36 14 true negative 14 14 false positive 0 0 false negative 1 23 sensitivity 97.29 (84.19-99.86) 37.84 (22.94-55.2) specificity 100.0 (73.24-100.0) 100.0 (73.24-100.0) positive predictive value 100.0 (88.0-100.0) 100.0 (73.24-100.0) negative predictive value 93.33 (66.03-99.65) 37.84 (22.94-55.2) positive likelihood ratio na na negative likelihood ratio 0.03 (0.004-0.19) 0.62 (0.48-0.80) na: not applicable; data are presented with 95% confidence interval. table 3: screening performance characteristics of ultrasound performed by radiologist and emergency physician in detection of increased gallbladder wall thickness characteristics radiologist emergency physician true positive 38 28 true negative 9 10 false positive 4 3 false negative 0 10 sensitivity 100.0 (88.57-100.0) 73.68 (56.61-86.02) specificity 69.23 (38.88-89.64) 76.92 (45.98-93.84) positive predictive value 90.0 (76.45-96.90) 90.03 (73.10-97.47) negative predictive value 100.0 (62.88-100.0) 50.0 (27.85-72.15) positive likelihood ratio 3.25 (1.44-7.34) 3.19 (1.16-8.77) negative likelihood ratio na 0.34 (0.19-0.61) na: not applicable; data are presented with 95% confidence interval. 3. results 61 patients were included in the study, but 10 patients were excluded due to unavailability of pathology results. finally, the data of 51 patients with the mean age of 42.3±15.8 (17-81) years were analyzed (82.4% female). table 1 shows the ultrasonography findings of gallbladder by emergency medicine resident and radiologist and their agreement rate, separately. the overall agreement between emergency medicine resident and radiologist in ultrasonographic diagnosis of cholecystitis was 0.421 (95% ci: 0.118-0.724). based on the pathology and surgical findings, acute cholecystitis was confirmed for all 51 (100%) patients. meanwhile, based on the ultrasonographic report of radiologist and emergency medicine resident only 45 (88.2%) and 34 (66.7%) patients, respectively, were diagnosed with cholecystitis. screening performance characteristics of ultrasonography by emergency medicine resident and radiologist in diagnosis of gallstone and wall thickness have been summarized in tables 2 and 3. screening performance characteristics of ultrasonography by radiologist for detection of gallstone (p = 0.010) and gallbladder wall thickness (p < 0.0001) were significantly better than emergency medicine resident. 4. discussion based on the results of the present study, it seems that relying solely on ultrasonography for making a decision regardthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com j. tootian tourghabe et al. 4 ing surgery of patients with pain in the right upper quadrant of their abdomen suspected with cholecystitis is not accurate enough. however, the screening performance characteristics of ultrasonography by radiologist in detection of gallstones and increased thickness of gallbladder wall were significantly better. numerous studies have been done on the diagnostic value of ultrasonography in detection of gallbladder problems, which has resulted in performance of many systematic reviews and meta-analyses for this purpose. for example, kiewiet et al. by evaluating 26 studies showed that sensitivity and specificity of ultrasonography in diagnosis of acute cholecystitis are 82% and 81%, respectively. however, in spite of performing subgroup analyses in the mentioned meta-analysis, no attention was paid to the role of the operator performing ultrasonography (12). ultrasonography being operator-dependent is a matter that, as clearly confirmed in the present study, affects the diagnostic value of ultrasonography. overall, much controversy exists between the studies regarding the value of ultrasonography in detection of gallstones. this controversy can be due to many reasons, one of which is dependence of ultrasonography on the operator’s skill. in comparison to the present study, the sensitivity of ultrasonography performed by an emergency medicine specialist reported by shekarchi et al. was higher (89.58% versus 77.08%). the cause of this difference might be the difference in the gold standard of these studies. in the present study, pathologic result was chosen as the gold standard, but in shekarchi et al. study, the results of ultrasonography performed by radiologist was considered as the gold standard (11). by assessing 164 patients in their study, villar et al. showed that diagnosis based on evidence of stone in ultrasonography alone has excellent sensitivity and negative predictive value in diagnosis of acute cholecystitis, even more than when a combination of symptoms is used (13). however, the retrospective nature of villar et al. study is its most important limitation. therefore, for answering the question “which symptoms should be used for diagnosis of cholecystitis in ultrasonography?”, it is suggested to perform more studies in this regard. it seems that for improving the screening performance characteristics of gallbladder ultrasonography by emergency medicine residents for detection of stone and increase in its wall thickness more training, practice and repetition is needed for improving their diagnostic skill. 5. limitation the most important limitation of the present study is the small number of the patients included (51 patients). this small sample size might have affected the diagnostic value reported. however, considering the surgical and pathology findings as the gold standard is one of its most important strong points. 6. conclusion based on the results of the present study, it seems that relying solely on ultrasonography for making a decision regarding surgery of patients with pain in the right upper quadrant of their abdomen suspected with cholecystitis is not accurate enough. however, the screening performance characteristics of ultrasonography by radiologist in detection of gallstones and increased thickness of gallbladder wall were significantly better. 7. appendix 7.1. acknowledgements all the personnel of the emergency department of imam reza hospital are sincerely thanked for their cooperation in performance of this project. 7.2. authors’ contribution all the authors of this article met the criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support all the costs of the present study were paid by the researchers. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. eskelinen m. diagnostic approaches in acute cholecystitis; a prospective study of 1333 patients with acute abdominal pain. theor surg. 1993;8:15-20. 2. brewer rj, golden gt, hitch dc, rudolf le, wangensteen sl. abdominal pain: an analysis of 1,000 consecutive cases in a university hospital emergency room. the american journal of surgery. 1976;131(2):219-23. 3. kimura y, takada t, kawarada y, nimura y, hirata k, sekimoto m, et al. definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: tokyo guidelines. journal of hepato-biliary-pancreatic sciences. 2007;14(1):15-26. 4. ebrahimi a, yousefifard m, kazemi hm, rasouli hr, asady h, jafari am, et al. diagnostic accuracy of chest ultrasonography versus chest radiography for identification of 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yousefifard m, baikpour m, ghelichkhani p, asady h, nia ks, jafari am, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. emergency. 2016;4(1):1. 9. summers sm, scruggs w, menchine md, lahham s, anderson c, amr o, et al. a prospective evaluation of emergency department bedside ultrasonography for the detection of acute cholecystitis. annals of emergency medicine. 2010;56(2):114-22. 10. kendall jl, shimp rj. performance and interpretation of focused right upper quadrant ultrasound by emergency physicians. journal of emergency medicine. 2001;21(1):7-13. 11. shekarchi b, hejripour-rafsanjani s-z, shekar-rizfomani n, chahardoli m. emergency department bedside ultrasonography for diagnosis of acute cholecystitis; a diagnostic accuracy study. emergency. 2018;6(1):11. 12. kiewiet jjs, leeuwenburgh mmn, bipat s, bossuyt pmm, stoker j, boermeester ma. a systematic review and meta-analysis of diagnostic performance of imaging in acute cholecystitis. radiology. 2012;264(3):708-20. 13. villar j, summers sm, menchine md, fox jc, wang r. the absence of gallstones on point-of-care ultrasound rules out acute cholecystitis. journal of emergency medicine.49(4):475-80. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e36 or i g i n a l re s e a rc h predictors of out of hospital cardiac arrest outcomes in pre-hospital settings; a retrospective cross-sectional study elham navab1, maryam esmaeili1, nastaran poorkhorshidi2, rasoul salimi3, afshin khazaei4∗, abbas moghimbeigi5 1. critical care and geriatric nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. student research committee, faculty of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, besat hospital, hamadan university of medical sciences, hamadan, iran. 4. intensive care and management nursing department, school of nursing and midwifery, hamadan university of medical sciences, hamadan, iran. 5. professor of epidemiology and biostatistics, department of biostatistics and epidemiology, school of public health, hamadan university of medical sciences, hamadan, iran. received: april 2019; accepted: june 2019; published online: 10 july 2019 abstract: introduction: different potential factors can affect the outcomes of out of hospital cardiac arrest (ohca). the present study aimed to identify important factors contributing to the return of spontaneous circulation (rosc) and survival to hospital discharge (shd) in these patients. methods: this cross-sectional study was conducted on all the ohca patients who underwent cardiopulmonary resuscitation (cpr) in emergency medical service (ems) of hamadan province during 2016-2017. all the relevant data were retrieved from three sources, according to utstein’s style. in addition, univariate and multivariate logistic regressions were employed to identify predictive factors of rosc and shd using spss software, version 20. results: among the 3214 eligible patients whose data were collected, most ohca patients were female (59.7%) with the mean age of 58 years. moreover, the majority of ohcas (77.8%) occurred at home during 8pm-8am (65.1%) and about 26.3% of ohcas were witnessed, with only 5.1% bystander-initiated cpr. furthermore, the median ambulance response time and cpr duration were 6.0 and 20 minutes, respectively. overall, rosc and shd success rates were 8.3 and 4.1%, respectively. bystander cpr was found to be the most effective predicting factor for the success rate of rosc (aor=3.26, p<0.001) and shd (aor=3.04, p<0.001) after adjusting for the utstein variables including the patients’ age, gender, cardiac disease history, arrest time, cpr duration, response time, being witnessed, bystander cpr, and endotracheal intubation (eti). conclusion: the overall success rates of rosc and shd were 8.3% and 4.1%, respectively. the age, ambulance response time, cpr duration, and cardiac disease history were negatively associated with the outcomes of rosc and shd, while being witnessed, bystander cpr, eti, and initial shockable rhythm were positively related to both of the above-mentioned outcomes. keywords: out-of-hospital cardiac arrest; emergency medical services; emergency medical technicians; cardiopulmonary resuscitation cite this article as: navab e, esmaeili m, poorkhorshidi n, salimi r, khazaei a, moghimbeigi a. predictors of out of hospital cardiac arrest outcomes in pre-hospital settings; a retrospective cross-sectional study. arch acad emerg med. 2019; 7(1): e36. ∗corresponding author: afshin khazaei; school of nursing and midwifery, shahid fahmideh blvd, hamadan, iran. postal code: 141973317. email: khazaei-a@razi.tums.ac.ir tel: 00989183143075 1. introduction out of hospital cardiac arrest (ohca) is considered as one of the leading causes of mortality around the world due to its high incidence, low survival rate, and unpredictability, and has attracted much attention in recent years (1). the incidence of ohcas was reported to be an average of 84 events per each 100,000 population in 27 european countries this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. navab et al. 2 (2). more than 575,000 ohca cases occur annually in north america (3) and its social and clinical impact is so high that, the american heart association (aha) has recommended reporting the outcomes of ohcas (4). for this purpose, the clinical research network established the pan-asian resuscitation outcomes study in seven asian countries in 2010 (5). this network also focuses on improving the outcomes of prehospital and emergency care across the asia-pacific region by performing high-quality research in cardiopulmonary resuscitation (cpr). management and treatment of ohcas are regarded as the main challenges in the emergency medical services (ems), considering the demanding nature of ohca (1). furthermore, cpr is considered as one of the most important measures in ohcas, which is a vital and effective procedure for determining the patient’s final outcome (1). although resuscitation knowledge has dramatically increased over the past few decades, no significant improvement is observed regarding the rate of return of spontaneous circulation (rosc) and survival to hospital discharge (shd) among ohca patients (6, 7). the latest cpr protocol (2015) has been recommended by the aha concerning guidance on ohca care including basic life support (bls) and advanced life support (als) care (8). these interventions are performed by ems in most countries (almost 60%) with substantial variations in cpr outcome (9). accordingly, access to basic, accurate, and reliable data related to ohca outcomes, and their related underlying factors such as the characteristics of patients and ohca are considered potentially effective factors in this regard. in other words, it provides opportunities for the researchers and policymakers, as well as those seeking to collect ohca-related data to use appropriate scientific approaches for prioritizing the resources, monitoring the national trends in ohca survival, reducing ohcarelated costs, promoting high-quality research, and improving ohca care (3, 10). therefore, due to scarcity of data in this regard, the present study primarily sought to determine the success rate of rosc and shd and identify the most influential factors. 2. methods 2.1. study design and setting the current multicenter cross-sectional study was conducted in the emergency medical service center of hamadan province (located in the west of iran), which included 20 urban and 30 road bases with the population of about two million people, during (april) 2016-(february) 2017. in this setting, all of the steps of cpr were performed based on the american heart association guidelines for cpr (2015), which required any deployed technician in ohca-related missions to provide basic and advanced life support care according to the guidelines. the present research was approved by ethics committee of hamadan university of medical sciences (no: ir.umsha.rec.1396.808). 2.2. participants all data of ohca patients treated by the emergency medical technicians (emts) at urban bases were collected retrospectively. the inclusion criteria consisted of ohca patients aged ≥18 years and the presumed cardiac etiology transported to the hospital by the emts. the exclusion criteria encompassed a non-cardiac cause of ohca, incomplete documents and cases with missing data, emts witnessing ohca, patients who were obviously dead at the scene (i.e., rigor mortis, lividity, decomposition, or decapitation) with no attempt at cpr by the emts, and those who achieved rosc or available cardiac support at the scene before the arrival of the emts. 2.3. data gathering the 2015 utstein resuscitation registry style was employed for recording ohca reports (11). all data were obtained from three sources including the registration system of information and statistics, patient care report form, and hospital information system. patients were excluded if cardiac arrest occurred in a clinic or where other emergency providers were attending to the patient. the data extracted for analysis included patients’ characteristics such as gender and age, as well as a history of cardiac diseases and ohca characteristics including the time of arrest (i.e., 8am-8pm/8pm-8am), event being witnessed, the provision of bystander-initiated cpr, the location of cardiac arrest (home/public), ambulance response time (defined by the time interval between a call and cpr initiation), initial shockable rhythm, cpr duration, endotracheal intubation (eti), and outcome (rosc and shd). 2.4. statistical analysis continuous variables were expressed as mean ± standard deviation (sd) or median and interquartile ranges (iqrs) where appropriate. furthermore, categorical variables were demonstrated as frequency and percentage. additionally, univariate (in each group) and multivariate (for the adjusted model) logistic regressions were applied to identify rosc and shd predictive factors through an association between continuous and categorical variables. the potential confounding variables in the final adjusted model were selected by a forward selection (wald) method (i.e., entering [0.005] and removing [0.10] predictors). in addition, utstein (a set of guidelines for uniform reporting of cardiac arrest) factors were utilized to select all the covariates that were recommended for reporting ohca-related data (12). the area under the receiver operating characteristic (roc) curve of the final model for predicting the probability of rosc and shd were calculated. the odds ratios with 95% confidence intervals (ci) were calculated as well. eventually, all the statistical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e36 figure 1: flowchart of patient enrollment. rosc: return of spontaneous circulation; emts: emergency medical technicians, ohca: out-of-hospital cardiac arrest. analyses were performed using the ibm spss statistics software, version 20. 3. results 3.1. baseline characteristics of studied cases 4244 ohca reports were evaluated, among which 1030 were excluded (figure 1). finally, 3214 patients with the mean age of 58.47 ± 12.10 years were included in the final analysis (59.7% female). the rate of shd was higher in females (4.4% vs. 3.7%; p = 0.313) while the rate of rosc was higher in males (8.1% vs. 8.6%; p = 0.580). most ohcas occurred at home (77.8%) and during 8pm-8am (65.1%). 26.3% of the ohcas were witnessed with a total of 5.1% bystanderinitiated cpr and most of the witnessed ohcas were observed in the public, compared to home (2.8% vs. 1.7%). the median ambulance response time and cpr duration were 6.0 (iqr: 4-9) and 20 (iqr: 12-33) minutes, respectively. regarding the initial arrest rhythm, the cases had mainly shown non-shockable (76.4%) rhythms, while most of the shockable rhythms were found in patients with a history of heart disease (13.8% vs. 9.8%). the number of successful rosc (16.9% vs. 4.7%) and shd (7.0% vs. 2.6%) cases was higher in patients with no history of heart disease and initial shockable rhythm. the rate of out-of-hospital eti placement was only 21.4%. in general, the success rates of rosc and shd were 8.3% and 4.1%, respectively. additional details of the patients’ characteristics are presented in table 1. 3.2. results of univariate and multivariate analysis tables 2 and 3 represent the univariate and multivariate logistic regression analyses of rosc and shd effective factors. based on unadjusted regression, bystander cpr and initial shockable rhythm were the most important factors influencing rosc and shd, respectively. bystander cpr was the most effective predicting factor for rosc (aor: 3.26, p<0.001) and shd (aor: 3.04, p<0.001) in ohca patients after adjusting for nine variables including the patients’ age, gender, cardiac disease history, the time of arrest, cpr duration, response time, being witnessed, bystander cpr, and endotracheal intubation (eti). roc curve of the final model is presented in figure 2. the specificity and positive predictive value of the predicting model for shd were 77.1% (95% ci: 74.3-79.9) and 77.2% (95% ci: 73.1-81.3), respectively. 4. discussion based on the results of the present study, the age, ambulance response time, cpr duration, and cardiac disease history were negatively associated with the outcomes of rosc and shd while being witnessed, bystander cpr, eti, and initial shockable rhythm were positively related to both of the above-mentioned outcomes. the overall success rates of rosc and shd were 8.3% and 4.1%, respectively, among the patients who underwent cpr by emts. the rate is low compared to that of the other studies in this area. based on the reports, the results of ohca registries regarding shd rate ranged from 7.5% to 10.8% in the united states and europe (13, 14). conversely, this rate was found to be only 5.4% of ohca patients in the pan-asian resuscitation outcomes study registry (15) and a meta-analysis achieved a pooled shd rate of 7.6% (12). based on the findings of previous studies (16, 17), age is regarded as the predictor of ohca outcome. the shd rate of the elderly ohca patients compared to younger patients was approximately half (18). in the present study, the mean ages of the patients with rosc and shd, were nearly 4 and 3 years less than that of the other patients, respectively. in addition, the unadjusted analysis revealed that each year increment in the age decreased the probability of rosc and shd by 1.03% and 1.04%, respectively. furthermore, in the adjusted regression analysis, age still had a significant inverse association with rosc (or: 0.97, p<0.001) and shd (or: 0.98, p=0.011), the details of which are provided in tables 2 and 3. witnessed cardiac arrest with cpr initiation by bystanders, preferably before the arrival of emts, is regarded as one of the important predictive factors in ohca outcome, which can increase shd about 40% and improves the neurological symptoms of the patients (19, 20). more importantly, timely bystander cpr can improve the outcomes despite the prolonged on-scene this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. navab et al. 4 table 1: comparing the baseline characteristics of out of hospital cardiac arrest cases based on the return of spontaneous circulation (rosc) and survival to hospital discharge (shd) variable rosc shd no (n=2941) yes (n=273) no (n=3088) yes (n=126) age (year) mean ± sd 58.1 ± 11.7 54.9 ± 14.8 57.8 ± 13.1 54.9 ± 12.0 gender female 1747 (91.9) 153 (8.1) 1817 (95.6) 83 (4.4) male 1201 (91.4) 113 (8.6) 1266 (96.3) 48 (3.7) cardiac history yes 1957 (93.7) 132 (6.3) 2018 (96.6) 71 (3.4) no 991 (81.18) 134 (11.9) 1065 (94.7) 60 (5.3) witnessed arrest yes 746 (88.2) 100 (11.8) 512 (95.5) 24 (4.5) no 2195 (92.7) 173 (7.3) 2300 (97.1) 68 (2.9) cpr by bystander yes 129 (72.1) 34 (29.0) 146 (89.6) 17 (10.4) no 2819 (92.4) 232 (7.6) 2937 (96.3) 114 (3.5) shockable rhythm yes 651 (85.9) 107 (14.1) 707 (93.3) 51 (6.7) no 2297 (93.5) 159 (6.5) 2276 (96.7) 80 (3.3) arrest location home 2112 (92.8) 163 (7.2) 2194 (96.4) 81 (3.6) public 836 (89.0) 103 (11.0) 889 (94.7) 50 (5.3) response time (minutes) mean ± sd 6.81 ± 3.35 4.73 ± 2.65 6.74 ± 3.32 4.27 ± 3.03 cpr duration (minutes) mean ± sd 22.4 ± 12.88 16.9 ± 10.40 23.1 ± 12.91 17.1 ± 8.35 arrest time day 962 (92.3) 80 (7.7) 1011 (97) 31 (3.0) night 1986 (91.4) 186 (8.6) 2072 (95.4) 100 (4.6) eti yes 613 (88.6) 79 (11.4) 658 (95.1) 34 (4.9) no 2235 (92.6) 187 (7.4) 2425 (96.2) 97 (3.8) data are presented as mean ± standard deviation (sd) or number (%). cpr: cardiopulmonary resuscitation; eti: endotracheal intubation. cpr duration: was defined as the time from initiation of cpr by emergency medical technicians to prehospital return of spontaneous circulation. table 2: effective factors of return of spontaneous circulation (rosc) in out-of-hospital cardiac arrest cases based on univariate and multivariate regression analyses variable (reference) univariate multivarate or (95% ci) p value aor (95% ci) p value patient age 0.96 (0.95-0.97) < 0.001 0.97 (0.95-0.98) < 0.001 gender (male) 1.07 (0.83-1.38) 0.580 arrest time (night) 0.88 (0.67-1.16) 0.394 arrest location (home) 1.59 (1.23-2.06) < 0.001 1.47 (1.94 -1.11) 0.007 cpr duration 0.95 (0.94-0.96) < 0.001 0.95 (0.93-0.96) < 0.001 history of cardiac disease (no) 0.49 (0.38-0.64) < 0.001 0.54 (0.40 0.72) < 0.001 witnessed (no) 1.46 (1.12-1.90) 0.005 bystander cpr (no) 3.20 (2.14-4.78) < 0.001 3.26 (2.08 5.12) < 0.001 response time 0.79 (0.75-0.83) < 0.001 0.80 (0.76-0.84) < 0.001 eti (no) 1.60 (1.21-2.12) 0.001 1.63 (1.21 2.20) 0.001 shockable rhythm (no) 2.37 (1.83-3.08) < 0.001 1.86 (1.41 -2.46) 0.001 ci: confidence interval; cpr: cardiopulmonary resuscitation; eti: endotracheal intubation; or: odds ratio; aor: adjusted odds ratio (adjusted for patients’ age, gender, arrest location, history of cardiac disease, time of arrest, cpr duration, response time, witnessed, bystander cpr and endotracheal intubation and shockable rhythm). times by emts (21). in some advanced countries, cpr is increasingly performed by bystanders, the rates of which have this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e36 figure 2: area under the receiver operating characteristic (roc) curve of adjusted logistic regression model for predicting the return of spontaneous circulation (0.771 (95% ci: 0743 – 0.799)) and survival to hospital discharge (0.772 (95% ci: 0.731– 0.813)). table 3: effective factors of survival to hospital discharge (shd) in out-of-hospital cardiac arrest cases based on univariate and multivariate regression analyses variable (reference) univariate multivarate or (95% ci) p value aor (95% ci) p value patient age 0.98 (0.96-0.99) 0.010 0.98 (0.96-0.99) 0.011 gender (male) 0.83 (0.57-1.19) 0.314 arrest time (night) 0.63 (0.42-0.95) 0.030 arrest location (home) 1.52 (1.06-2.18) 0.022 cpr duration 0.73 (0.68-0.79) < 0.001 0.96 (0.94-0.97) < 0.001 history of cardiac disease (no) 0.62 (0.43-0.88) 0.009 0.59 (0.41-0.85) 0.006 witnessed (no) 1.86 (1.30-2.66) 0.001 bystander cpr (no) 3.00 (1.12-5.12) < 0.001 3.04 (1.73-5.35) < 0.001 response time 0.83 (0.78-0.89) < 0.001 0.74 (0.69-0.80) < 0.001 eti (no) 1.29 (0.86-1.92) < 0.001 shockable rhythm (no) 2.14 (1.49-3.07) < 0.001 1.79 (1.23-2.6) 0.002 ci: confidence interval; cpr: cardiopulmonary resuscitation; eti: endotracheal intubation; or: odds ratio; aor: adjusted odds ratio (adjusted for patients’ age, gender, arrest location, history of cardiac disease, time of arrest, cpr duration, response time, witnessed, bystander cpr and endotracheal intubation and shockable rhythm). reached 50% (13). however, bystander cpr rate was very low in both witnessed (2.0%) and non-witnessed (3.1%) cases in the current study. the result becomes more prominent when cpr by bystanders was found to increase the chances of successful cpr and shd to 1.50 (or: 3.89 vs. 2.59, p=0.001) and 1.35 fold (or: 3.16 vs. 2.33, p<0.001) in the unadjusted regression, compared to the non-witnessed. the results are consistent with those of other studies regarding ohcas. rajan et al. indicated that quick and uninterrupted cpr by bystanders before the arrival of the ambulance at the scene can lead to more than two-fold increase in the one-month survival rate of the patients (22). initial shockable rhythm (i.e., ventricular tachycardia) is another essential factor in ohca, and the success rate of rosc and shd dramatically increases in case of timely shock using defibrillator (23). based on the results of the present study concerning the unadjusted regression, patients with an initial shockable rhythm shocked by the emt had a higher chance of cpr success (or: 2.37, p<0.001) and shd rate (or: 2.14, p<0.001) compared to those with a non-shockable rhythm. when adjusted for other variables, the initial shockable rhythm was still an important effective factor on the outcomes of cpr (aor: 1.86, p=0.001) and shd (aor: 1.79, p=0.002) compared to the non-shockable rhythm (tables 2 and 3). in this regard, public access defibrillation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. navab et al. 6 and the related programs such as leadership behavior, training, competency, and experience in managing emergencies (24), especially in the areas with a higher incidence rate of ohca can be effective in cpr success and improving the survival rate of the victims (25). furthermore, stammet et al. found that ohca patients who underwent cpr by a bystander and those who used automated external defibrillators (aed) had almost 1.2 and 2.28 times better cpr outcomes, respectively, compared to those who underwent cpr without the aed and the patients with non-witnessed ohca (26). additionally, the results of a systematic review and meta-analysis demonstrated that survival chance and favorable neurological status were nearly doubled when the aed device was used by a bystander during the cpr (20). aed device is widely used in cardiac arrests in public places since almost 20% of the ohca cases occur in such places (27). as shown in table 2, the highest success rates regarding cpr (11.0% vs. 7.2%) and shd (5.3% vs. 3.6%) in ohcas belong to public places due to higher probability of the arrest being witnessed. unfortunately, no aed devices existed in public places of hamadan province, leading to an increase in the number of ohca patients. given the findings of evidencebased studies, the american heart association and the european resuscitation council recommended to implement programs related to quick access to the defibrillator device in their 2015 guidelines (28, 29). therefore, the necessity of installing aed devices in public places and implementing the general cpr training program at the community level are considered factors that can play a key role in ohca outcomes in the present context. in addition, the time of arrest (night/day), as well as its effect on the outcomes of ohca was investigated in the current study. the result of univariate regression indicated that the time of arrest only affected shd (or: 0.63, p=0.030), while it no longer showed an effect on shd in the multivariate regression and the difference in survival of the subgroups disappeared when adjusted for the confounders. in line with the result of the present study, in a meta-analysis study, lin et al. concluded that patients who had an ohca during the night had lower 1-month/inhospital survival, compared to those with daytime ohca (30). additionally, ho afw et al. (31) reported that the 30-day survival of ohca cases happening at night was lower than those happening in the daytime among the pan-asians with an adjusted odds ratio of 0.79. perhaps, one of the reasons for the effect of the arrest time on cpr outcomes in the current study is that ohca at night is less likely to be witnessed (7.7 vs. 20.1%, p<0.001) and receive bystander cpr (2.0 vs. 3.1%, p=0.05). furthermore, the duration of prehospital cpr before transporting the patients to a hospital is regarded as another key component in ohca outcomes (12). despite the major advances in cpr, no comprehensive agreement was reached with respect to the duration of cpr in ohca and acceptable time for its termination. based on the results of the present study, the mean duration of cpr in the successful rosc was less than the unsuccessful rosc, and the shd versus non-shd. according to previous reports, reynolds et al. (32) determined that rosc occurs in 89.7% of ohca patients who undergo cpr within 16 minutes. additionally, cooper et al. reported that the cpr duration of less than 14 minutes caused a 62% survival rate among ohca patients while it was 20% for cpr durations over 15 minutes (33). in addition, according to funada et al., cpr duration over 26 minutes led to rosc failure in ohca patients (34). furthermore, the results of both adjusted and unadjusted regression analyses of the current study demonstrated that cpr duration was independently and inversely associated with successful rosc and shd (tables 2 and 3). after confounder adjustment, every minute increase in cpr duration was found to be related to a 9% reduction in the odds of successful cpr (aor 0.95, ci: 0.93-0.96, p<0.001) and shd (aor 0.95, ci: 0.94-0.97, p<0.001). dyson et al. obtained the same result by assessing the impact of cpr duration on shd in their study (35). therefore, the lack of an appropriate termination of resuscitation rule in bls and als care can lead to an increase in patient transport to the hospital, ineffective attempts, a waste of medical resources, and the exposure of tired emt and the public at the risk of accident due to the high-speed transport (36). however, there are still challenges that remain unsolved regarding appropriate determination of resuscitation termination for ohca patients (37). the survival rate of cardiac arrest decreases 5-10% for every minute that passes from the event (38). in this regard, the response time of the emergency medical service is regarded as one of the important factors associated with rosc and shd in ohca cases (39). in the current study, the mean ambulance response time in unsuccessful rosc was 1.43 times more than the successful rosc. furthermore, this comparison in nonshd and shd was 1.57 times, which confirmed a significant inverse relationship between ambulance response time and the success/failure of rosc and shd. additionally, the results of multivariate logistic regression test indicated that the success rates of rosc and shd dropped 1.24 and 1.33 times, respectively, for each minute of delay in initiation of cpr. a large body of research reported different results regarding the effect of the response time on cpr outcomes. for example, sladjana et al. found that higher shd and rosc rate is observed when cpr is performed within the first four minutes after the ohca (40). burger et al. demonstrated that if cpr is performed by a bystander and the mean ambulance response time increases from 1:04 to 9:47 minutes, the discharge rate reduces from 22.0% to 14.0%; while if no bystander cpr is performed and the mean ambulance response time increases from 1:10 to 9:47 minutes, the discharge rate drops from 12.9% to 6.4% (41). therefore, based on the findings, identifythis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e36 ing the areas and geographic locations with higher incidence of ohcas can help reduce the response time and improve the shd rate (40). in this regard, emergency operators can play an important role by using telephone cpr, training bystanders, and increasing the number of bystander cpr rate for improving favorable outcomes (42). finally, the effect of prehospital advanced airway management (aam) in ohca patients is still considered as a controversial issue (43). eti is regarded as the optimal method and the gold standard of aam in the prehospital setting (44, 45). performing it can be associated with improved odds of sustained rosc, shd, and favorable neurologic outcomes (43). based on the results of univariate regression, eti in ohca was an effective factor in the success of rosc (or:1.60, p=0.001) and shd (or:1.29, p<0.001), and this factor only correlated with rosc in the presence of other covariates in the adjusted model (or:1.63, p=0.001). benoit et al. (46) concluded that delay in eti was associated with decreased probability of rosc, which is in conformity with the results of the current study. in addition, izawa et al. demonstrated that a shockable rhythm determines the effect of eti placement on ohca and performing aam in patients with non-shockable rhythm showed better survival compared to those with a shockable rhythm (47). however, evaluating the effect of this factor on ohca outcomes is vital, which necessitates further investigation. in the end, since the study was conducted for patients over the age of 18 years, the results cannot be interpreted for those under the age of 18. also, 7.1% (230) of the information of patients who have suffered from ohca have been excluded due to incomplete information, most of which was related to the bystander-initiated cpr and initial shockable rhythm; therefore, the results of this study should be used with caution. the results of the present study revealed that the rate of success in rosc and shd in the emergency medical services of hamadan province was extremely low compared to those of previous studies. accordingly, the results of this study showed us that some modifiable predictive factors could improve the rosc and shd rate in a limited-resource setting such as the prehospital emergency. therefore, the two abovementioned outcomes can be applied to enhance rosc and shd rates by improving the important modifiable contributing factors such as provision of bystander-initiated cpr, eti, and reducing ambulance response time. 5. limitation one limitation of the current study was its retrospective design, so that the accuracy of data collection could not be monitored and there could be potential measured and unmeasured confounders, which may account for the observed outcomes. in the present study, the lack of an integrated system for recording the data of the patients who suffered from ohca after one month led to the impossibility of assessing two important factors, namely, neurological status and patient survival one month after the cardiac arrest and its association with cpr outcomes. furthermore, the lack of access to the aed device by the bystanders led to the impossibility of measuring the effect of using the defibrillator on the outcomes of cpr performed by the bystanders on ohca patients. 6. conclusion based on the results of the present study, age, ambulance response time, cpr duration, and cardiac disease history were negatively associated with rosc and shd outcomes, while being witnessed, bystander cpr, eti, and initial shockable rhythm were positively related to both of the abovementioned outcomes. the overall success rates of rosc and shd were 8.3% and 4.1%, respectively. 7. appendix 7.1. acknowledgements i am grateful to the director of the disaster and emergency medical management center of hamadan province for their help and support in processing and accessing information resources in the survey. 7.2. authors’ contribution elham navab, maryam esmaeili and afshin khazaei designed the study. rasoul salimi and nastaran poorkhorshidi aided in collecting data. abbas moghimbeigi analyzed the data and aided in interpreting the results. finally, all the above-mentioned authors discussed the results and contributed to the final manuscript. authors orcids elham navab: 0000-0002-5210-9070 maryam esmaeili: 0000-0002-4798-2270 nastaran poorkhorshidi: 0000-0001-6091-606x rasoul salimi: 0000-0002-6463-6046 afshin khazaei: 0000-0002-8063-3419 abbas moghimbeigi: 0000-0002-3803-3663 7.3. funding/support the present study was supported by the vice-chancellor of research and technology, hamadan university of medical sciences under grant number 9611247613. 7.4. conflict of interest the authors report no conflict of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. navab et al. 8 references 1. 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open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e20 ca s e re p o rt sudden death due to hydatid cyst emboli; a case report mohammad ali emam hadi1, fares najari1∗, leila soleimani1 1. department of forensic medicine, shahid beheshti university of medical sciences, tehran, iran. received: january 2018; accepted: march 2018; published online: 19 march 2018 abstract: echinococcosis is an infection caused in human by complex parasites that causes cystic hydatid disease. these infections are prevalent in most areas where livestock is raised in association with dogs. these parasites are found in all continents. slowly enlarging cysts generally remain asymptomatic until their size has expanded. here we present a case of sudden death following cyst emboli to the large veins and right heart of a young adult female. keywords: death, sudden; echinococcosis; embolism; case report © copyright (2018) shahid beheshti university of medical sciences cite this article as: emam hadi m, najari f, soleimani l. sudden death due to hydatid cyst emboli; a case report. emergency. 2018; 6 (1): e20. 1. introduction echinococcosis is an infection caused in human by complex parasites that causes cystic hydatid disease. these infections are prevalent in most areas where livestock is raised in association with dogs. these parasites are found in all continents. slowly enlarging echinococcal cysts generally remain asymptomatic until their expanding size or their occupation of space affects the spleen, lung, or brain (1-3). the liver and the lungs are the most common sites of these cysts. since a number of years elapses before cysts enlarge sufficiency to cause symptoms, they may be discovered incidentally on a routine x-ray or ultrasound study (4-6). sudden death following embolization of cysts to the large veins is a rare complication of this infectious disease. previously, some cases have been reported in this regard (7-9). here we report the autopsy findings of the deceased unknown woman who was referred to legal medical center of iran with history of dyspnea for 6 hours followed by death without any further medical documentation. 2. case presentation: the deceased was a young adult female, who was referred to kahrizak autopsy center, tehran, iran, by order of legal authority. with no significant medical history, the death was ∗corresponding author: fares najari; department of forensic medicine and toxicology, shohadaye tajrish hospital, shahrdari street, tajrish square, tehran, iran. postal code: 1981964771 tel: 00989123195140 email: fares.hospital@yahoo.com reported by neighbors and ems to the police center in suburb areas of tehran. the victim was seen 1 hour before announcing dead, while she was complaining about shortness of breath and heaviness on the chest, but refusing to go to the doctor because of attributing the symptoms to air pollution and common cold. neighbors called ems with exacerbation of symptoms. the patient was announced dead upon arrival of ems. the deceased didn’t have any family members and identification card (she was most probably an illegal immigrant from east borders of iran). the body was that of a 30 year old, well nourished, well developed, female according to color of hair, skin, and teeth. there was no peripheral edema of the extremities. there was no area of congestion, cyanosis, bruise and abrasion. there was normal hypostasis in the posterior parts of body and complete rigor mortis. scalp, skull, spine, membrane, and brain were normal. trachea and larynx were normal. no fracture, pathology or hemorrhage were detected. the pleural cavities had no fluid or adhesion; however, dilated vein was noticed on the surface of left lung (figure 1). while cutting large arteries and large veins of the heart, multiple cysts (well defined, bubble shaped, round objects covered by shiny white membrane) 3 cm in diameter started to emerge rapidly and were extracted from inferior vena cava vein and right chambers of the heart (figure 1). the heart was 300 grams in weight, appeared normal without any ruptured cyst in the chambers. fibrosis, hyperemia, or any sign of infarction or hypertrophy weren’t detected. valves appeared intact. coronary arteries were patent. there was no abnormality in large vessels. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. emam hadi et al. 2 figure 1: anterior view of thoracic cavity (left upper) and liver (right upper), cysts in right atrium and inferior vena cava (left and right lower). lungs weighed 300 grams. pulmonary tissue was congested. there were also several cysts in the pulmonary artery, which this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e20 formed saddle emboli. liver weight was 900 grams. the surface was course and adhesion bands to near structures made it hard to remove the organ en bloc (figure 1). in several cuts congestion, nutmeg liver, and multiple cysts appeared. by removing the liver a lot of cysts came out of inferior vena cava and occupied the abdomen cavity gall bladder, and spleen (figure 1). right kidney was not seen (previous surgery due to car accident). left contained 2 small simple cysts, which measured 1 cm in diameter full of yellow clear fluid. in cortex cuts, medulla, and parenchyma appeared normal. stomach and intestines contained ingested food and their mucous was intact. no ischemic change was seen in the cardiac tissue and brain was reported to be normal. in the pulmonary tissue, mild to moderate alveolar edema was seen. no evidence of hydatid cyst or remnants were observed in lungs neither microscopic nor macroscopic. toxicological samples from vitreous, gastric content, urine, liver, and bile were obtained, analyzed, and reported negative for alcohol (by gc-ms on vitreous), narcotic and other drugs (by tlc on gastric content, urine, liver, and bile). histopathology study of liver and lung cyst samples revealed the cyst had a white thin fibrous membrane, which contained a clear fluid and some grain like particles laminated membrane of hydatid cyst with scolices and hooklets. by analyzing autopsy, histopathology, and toxicology and history data the commission of three board certified forensic specialties decided to declare “cardiac arrest due to massive emboli by multiple hydatid cysts” as cause of death. 3. discussion an embolus is an intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin. the vast majority of emboli derive from a dislodged thrombus. less common types of emboli include fat droplets, bubbles of air or nitrogen, atherosclerotic debris, tumor fragments, bits of bone marrow, and amniotic fluid; emboli lodge in vessels resulting in partial or complete occlusion. depending on the site of origin, emboli can lodge anywhere in the vascular tree (10-12). the primary consequence of systemic embolization is necrosis of downstream tissue while embolization in the pulmonary circulation leads to hypoxia, hypotension, and right-sided heart failure. the consequence of embolization depends on the caliber of the occluded vessel, the collateral supply, and the affected tissues vulnerability to anoxia. in this case, multiple hydatid cysts originated from liver and moved through vena cava to the right side of the heart and pulmonary artery, which is compatible with definition of emboli. we didn’t witness any hypoxic change in tissue of the brain and heart; the reason may be the rapid onset of symptoms, which lasted only 1 hour before occurrence of death and compatible with the history. so the application of the term “sudden death” seems to be accurate for our case. it seems that along with ischemic cardiac problems and poisonings, cases such as the discussed one should also be considered in differential diagnosis of cause of death in young patients who face sudden death without any history of underlying illnesses. however, late diagnosis and weak clinical suspicion to rare cases such as this one might prevent the incharge physician from saving the life of such patients. 4. appendix 4.1. acknowledgements we would like to express our special thanks to the forensic center of tehran, iran. 4.2. author’s contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declared no potential conflict of interest with respect to the authorship and/or publication of this article. 4.4. funding none. 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to cardiac hydatid disease: imaging findings of unusual complication of hydatid cyst. european radiology. 2002;12(3):627-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references archives of academic emergency medicine. 2019; 7 (1): e66 rev i ew art i c l e ultrasonography in detection of renal calculi in children; a systematic review and meta-analysis mojtaba fazel1,2, mohammed i m gubari3, mahmoud yousefifard4∗, mostafa hosseini1,5 † 1. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 2. department of pediatrics, valiasr hospital, imam khomeini medical complex, tehran university of medical science, tehran. 3. community medicine, college of medicine, university of sulaimani, sulaimani, iraq. 4. physiology research center, iran university of medical sciences, tehran iran. 5. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: september 2019; accepted: october 2019; published online: 24 november 2019 abstract: introduction: although numerous studies have been done to evaluate the diagnostic value of ultrasonography in diagnosis of renal calculi in children, there is still no consensus. therefore, in the present systematic review and meta-analysis, we aimed to evaluate the diagnostic accuracy of ultrasonography in identifying renal stones in children. methods: a comprehensive search of the electronic databases including medline, embase, scopus and web of science was conducted up to july 2019. diagnostic accuracy studies in children were included. data was summarized and pooled. area under the curve (auc), sensitivity, specificity, diagnostic score and diagnostic odds ratio were reported with 95% confidence interval (95% ci). results: data from 7 articles were included. pooled analysis showed that the area under the curve of ultrasonography in diagnosis of pediatric renal calculi was 0.94 (95% ci: 0.92 to 0.96). the sensitivity and specificity of this diagnostic modality were 0.80 (95% ci: 0.70 to 0.87) and 1.00 (95% ci: 0.84 to 1.00), respectively. diagnostic score and diagnostic odds ratio of ultrasonography in detection of renal calculi were 110.32 (95% ci: 2.88 to 19.76) and 82362.41 (95% ci: 17.80 to 3.8 × 108), respectively. conclusion: overall, the low level of evidence indicates that sensitivity and specificity of ultrasonography in detecting renal calculi in children are 80% and 100%, respectively. however, due to the serious limitations of the included studies, well-designed prospective diagnostic accuracy studies are recommended for future studies. keywords: kidney calculi; ultrasonography; diagnostic imaging; pediatrics cite this article as: fazel m, gubari m i m, yousefifard m, hosseini m. ultrasonography in detection of renal calculi in children; a systematic review and meta-analysis. arch acad emerg med. 2019; 7(1): e66. 1. introduction renal calculi are a common cause of hematuria as well as abdominal and flank pains. statistics have shown a high incidence of this condition, with one in 10 people developing renal calculi. the prevalence of renal calculi in children has not been evaluated in population-based studies. however, local and hospital-based studies have shown an increase in ∗corresponding author: mahmoud yousefifard, physiology research center, school of medicine, iran university of medical sciences, hemmat highway, tehran, iran; email: yousefifard.m@iums.ac.ir; tel: +982186704771 † corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127 reported cases of pediatric renal calculi. the prevalence of renal calculi in 1999 was about 18.4 children per 100,000 population, compared to 57 children per 100,000 population in 2008 (1). although the prognosis of renal calculi in children is often good, mortality and persistent disability have also been reported in some cases. although computed tomography (ct) scans are the most important diagnostic method for renal calculi in children, the risk of exposure to radiation, which is associated with the risk of cancer and its high medical costs, is a limitation of its use. however, there is no evidence that ct scans lead to improvement of patient outcomes (despite their high sensitivity). these limitations of ct indicate the need for alternative diagnostic methods, which should be reliable in addition to preventing exposure to radiation and being inexpensive. ulthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 2 trasonography may be a reliable alternative for this purpose (2-5). high diagnostic speed and portability has made ultrasonography the first diagnostic step in many clinical conditions. however, the diagnostic accuracy of ultrasonography is highly dependent on the skill of the operator and is not very reliable in identifying parenchymal injuries and injuries that are free of bleeding or free fluid flow (6-8). yet, technological advancements in ultrasound equipment in recent years have improved the quality of images, especially their spatial resolution. consequently, with a brief training of physicians, the diagnostic sensitivity of the test can increase significantly. this has led to the use of ultrasonography in identifying various clinical conditions (9-11) and in some cases its performance is even better than other imaging modalities (9, 10, 12-14). although several studies have been done to evaluate the diagnostic value of ultrasonography in detection of renal calculi in children, there is still no consensus on this (15-17). systematic reviews and meta-analyses are one of the solutions that can be used to provide a reliable conclusion. in recent years, some review articles have been conducted to evaluate the value of ultrasonography and ct in identifying renal calculi in children. however, none of them have metaanalytically evaluated the value of these modalities in identifying renal calculi (15-19). therefore, in the present systematic review and meta-analysis, we aimed to evaluate the diagnostic accuracy of ultrasonography in identifying renal stones in children. 2. methods: 2.1. search strategy a comprehensive literature search of the electronic databases including medline, embase, scopus and web of science was conducted up to july 2019. a search strategy based on keywords related to ultrasound and ct scan including "ultrasound" or "sonography" or "ultrasonography" or "computed tomography scan" or "ct scan" or "tomography scan" in combination with words related to renal calculi including "renal stone" or "kidney stone" or "kidney calculi" or "renal calculi" or "urolithiasis" was performed. since the present meta-analysis focuses on child population, childrelated keywords were also included in the search strategy. to find additional articles, manual search was carried out using the references of relevant studies. keywords were selected as widely as possible so that no study would be omitted. although only human studies were included in the present meta-analysis, the human studies related filter was not used. the keywords used were obtained using mesh of pubmed database, emtree section of embase database and search in the title of related articles. furthermore, three strategies were employed for searching gray literature. firstly, the theses section of the proquest database was searched. secondly, authors of related articles were contacted to obtain unpublished or in-print data. finally, google search engine and google scholar were used to obtain additional resources. applying these strategies resulted in the inclusion of an additional article to the present meta-analysis. the query on the medline database (via pubmed) is presented in appendix (table s1). 2.2. eligibility criteria we included human diagnostic value studies, which were performed to evaluate the diagnostic accuracy of ultrasonography or ct scans in identifying renal calculi in children. however, review articles, studies performing ultrasonography after ct or radiography, and duplicate articles were excluded. 2.3. data extraction and risk of bias two independent researchers screened articles by title and abstract. afterwards, the full-texts of potentially relevant studies were obtained and studied in detail. next, each researcher selected eligible studies and summarized them based on a pre-designed checklist. in the event of a disagreement between the two researchers, a third reviewer studied the findings and resolved the existing disagreement by factual discussion with the other two researchers. extracted data included relevant information about sample characteristics (age, sex), sample size, sampling method (convenience / consecutive), study design (retrospective, prospective), probe for ultrasonography, operator and interpreter of ct scan and ultrasonography findings, reference test, true positive (tp), false positive (fp), true negative (tn), false negative (fn), outcome (presence or absence of stone) and potential bias. the risk of bias assessment of the studies was performed based on the proposed 14-item quality assessment of diagnostic accuracy studies (quadas-2) tool (20). 2.4. statistical analysis analyzes were performed using stata 14.0 statistical program using the "midas" module. tp, fp, tn and fn were recorded in patients with renal kidney in each study. these numbers were used to calculate the area under the curve (auc), sensitivity, specificity, diagnostic score and diagnostic odds ratio with 95% confidence interval (95% ci). furthermore, a mixed-effects binary regression model, which is a kind of random effect model, was used to perform the analyses. heterogeneity assessment was evaluated via i2 tests (21). deek’s funnel plot was also used to check publication bias. finally, a subgroup analysis was performed using a bivariate mixed-effects binary regression model to identify the source of heterogeneity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e66 3. results: 3.1. study characteristics initial search of databases resulted in 2512 non-redundant articles, 17 of which were reviewed in full. finally, data from 7 studies were included in the present meta-analysis (22-28) (figure 1). these studies included data from 1382 children with suspected renal calculi. 211 cases were tp, 1116 tn, 1 fp, and 54 fn. except for one study, ct scan was the reference test. only one study had reported the type of probe and its frequency in detail. two studies stated that probe selection was based on patient status. the operator of the ultrasonography device was pediatric sonographer in one study and radiologist in 3 studies. operator was not reported in other studies. three studies reported ultrasonography criteria for diagnosis of renal calculi. table 1 presents a summary of the included studies. 3.2. risk of bias and publication bias the risk of bias in patient selection was high in 5 studies. in other cases, the risk of bias was low or unclear. also, all studies regarding the patient selection, index test and reference standard sections were applicable to the present metaanalysis (table 2 and figure 2). however, some degrees of publication bias were observed in the included studies (p = 0.04) (figure 2). 3.3. diagnostic performance of ultrasonography pooled analysis showed that the auc of ultrasonography in diagnosis of pediatric renal calculi was 0.94 (95% ci: 0.92 to 0.96) (figure 3). sensitivity and specificity of this diagnostic modality were 0.80 (95% ci: 0.70 to 0.87) and 1.00 (95% ci: 0.84 to 1.00), respectively (figure 4). diagnostic score and diagnostic odds ratio of ultrasonography in renal calculi detection were 110.32 (95% ci: 2.88 to 19.76) and 82362.41 (95% ci: 17.80 to 3.8 ãů 108), respectively (figure 5). subgroup analysis showed that ultrasonography operator (p = 0.14), reporting ultrasonography criteria (p = 0.09) and study performance year (p = 0.33) did not have any effect on the sensitivity of ultrasonography but had a slight effect on its specificity (p <0.0001) (table 3). 4. discussion the present meta-analysis was the first to quantitatively summarize the findings reported in the literature on the value of ultrasonography in identifying renal calculi in children. the findings of this study showed that ultrasonography had 80% sensitivity and 100% specificity in identifying renal calculi in children. in other words, ultrasonography is an excellent diagnostic test for renal calculi, and only one case of false positive has been reported. however, it is not a perfect screening tool because its sensitivity is 80% and 54 false negatives have been observed. in a systematic review tasian and copelovitch stated that ultrasound should be used as the first diagnostic modality for screening of renal calculi in children and ct scan should be used only when ultrasonography findings are negative and the suspicion of nephrolithiasis remains high (17). the conclusion reported by tasian and copelovitch on the use of ultrasound as the first diagnostic modality is inconsistent with the findings of the present study, because pooled sensitivity of ultrasonography in the present meta-analysis is 80%. although tasian and copelovitch stated in their study that patients with high suspicion to nephrolithiasis and negative ultrasonography should undergo a ct scan, this is not clinically feasible because the patient certainly had at least one important clinical sign that led the physician to suspect renal calculi. according to this recommendation, virtually all patients with non-diagnostic ultrasonography should undergo a ct scan. contrary to the tasian and copelovitch study, we do not recommend the use of ultrasonography as the first modality. in another systematic review, hoppe and kemper referred to ultrasonography as a modality with more advantages than other imaging tools in identifying renal calculi in children, including avoiding exposure to ionizing radiation, easy detection of hydronephrosis, and identifying some anatomical aspects of the urinary tract. however, they stated that ultrasonography is not as sensitive as ct scan in identifying small stones and the skill of the operator plays an important role in its diagnostic value (15). the findings of this study are in line with the present study. subgroup analysis showed that differences in ultrasonography, reporting of ultrasonography criteria for renal stone diagnosis and study performance year did not affect sensitivity. although the effect of these factors on specificity was statistically significant, it was clinically insignificant as the specificity of ultrasonography changed by only 1%. the use of a suitable probe is essential in increasing the sensitivity and specificity of ultrasonography (29). however, only one of the articles included in the present study provided the details of the probe used. although the probability of using an inappropriate transducer is low, failure to report this issue precludes reaching conclusions about the role of probe type in performance of ultrasonography for pediatric renal calculi diagnosis. operator dependence of ultrasonography is a well-established fact (30-33). however, 3 studies did not report ultrasonography operator. this is a serious limitation as it cannot be ascertained whether the ultrasound operator is sufficiently skilled in the research performed or not. although a subgroup analysis based on ultrasonography operator was done in the present meta-analysis, comparisons were made between studies that reported operator expertise and those that didn’t. in other words, since the expertise of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 4 the operator is unclear in some studies, the analysis of this section cannot be reliable. studies have used various criteria to identify renal calculi, including acoustic shadowing, echogenic focus and twinkling artifact. however, 3 of the 7 studies did not specify which ultrasonic markers they used to identify renal calculi. in addition, it should be noted that it is difficult to detect calculi in collapsed ureter using ultrasonography (29). in these cases, the patient should be well hydrated and the bladder acts as a sonic window to identify ureteral stones. therefore, in emergency situations, when the patient is dehydrated and there is insufficient time to hydrate the patient, ultrasonography will be of limited use in identifying urinary tract calculi. another limitation of the included studies was the retrospective design in 5 studies. the retrospective design may increase the risk of bias in the reported findings. in retrospective studies, both the findings of ultrasonography and ct scan are available. therefore, ultrasonography findings may be interpreted with knowledge of the ct scan findings. this cannot be completely eliminated from retrospective studies. in addition, in many cases controlling for confounding factors such as the interval between ultrasound and ct scans, the type of probe and the operator of the ultrasonography device is not possible. therefore, the findings reported in these studies appear to be of low level of evidence. 5. conclusion in conclusion, the low level of evidence indicates that sensitivity and specificity of ultrasonography for detecting renal calculi in children are 80% and 100%, respectively. however, due to the serious limitations of the included studies, welldesigned prospective diagnostic accuracy studies are recommended for future studies. 6. appendix 6.1. acknowledgements none. 6.2. authors contributions study design: mahmoud yousefifard and mostafa hosseini data gathering: mojtaba fazel, mohammed i m gubari and mahmoud yousefifard analysis: mostafa hosseini drafting the paper: mojtaba fazel, mohammed i m gubari critically revised: mahmoud yousefifard and mostafa hosseini authors orcids mojtaba fazel: 0000-0003-0463-4257 mohammed i m gubari: 0000-0002-2873-3981 mahmoud yousefifard: 0000-0001-5181-4985 mostafa hosseini: 0000-0002-1334-246x 6.3. funding support this research has been supported by tehran university of medical sciences & health services grant (id number: 95-01184-31859). 6.4. conflict of interest there is 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detection of pulmonary contusion; a systematic review and metaanalysis. emergency. 2015;3(4):127. 32. rahimi-movaghar v, yousefifard m, ghelichkhani p, baikpour m, tafakhori a, asady h, et al. application of ultrasonography and radiography in detection of hemothorax; a systematic review and meta-analysis. emergency. 2016;4(3):116. 33. yousefifard m, baikpour m, ghelichkhani p, asady h, darafarin a, esfahani mra, et al. comparison of ultrasonography and radiography in detection of thoracic bone fractures; a systematic review and meta-analysis. emergency. 2016;4(2):55. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 6 t a b le 1 : s u m m a ry o f in cl u d e d st u d ie s a u th o r s a m p le si ze s a m p li n g d es ig n a g e (y ea r) n o .b o ys g o ld en st a n d a rd p ro b e o p er a to r u s st o n e cr it er ia u s to c t in te rv a l (h o u rs ) t p t n f p f n h u , 2 0 1 0 (2 2 ) 1 0 6 2 p ro sp e ct iv e 1 to 1 0 5 6 5 c t u ro g ra p h y h ig h fr e q u e n cy p ro b e r a d io lo g is t n r n r 3 6 1 0 1 3 0 1 3 jo h n so n , 2 0 1 1 (2 3 ) 4 2 r e tr o sp e ct iv e 3 to 2 5 2 4 c t n r n r n r n r 3 7 1 0 4 p a lm e r, 2 0 0 5 (2 4 ) 5 4 r e tr o sp e ct iv e 3 to 1 8 2 8 c t n r n r n r n r 1 0 3 7 0 7 p a ss e ro tt i, 2 0 0 9 (2 5 ) 5 0 p ro sp e ct iv e 2 to 1 8 n r c t v a ri a b le p ro b e r a d io lo g is t a s 0 .5 to 8 2 6 1 6 0 8 r o b e rs o n , 2 0 1 8 (2 6 ) 6 9 r e tr o sp e ct iv e 5 to 1 9 3 5 c t v a ri a b le p ro b e p e d ia tr ic so n o g ra p h e r e f, t a ,a s 0 to 2 4 2 0 3 8 1 1 0 s m it h , 2 0 0 0 (2 7 ) 2 8 r e tr o sp e ct iv e 1 to 1 3 2 0 p a ti e n t fo ll o w u p n r n r n r n r 2 3 4 0 1 v e rh a g e n , 2 0 1 9 (2 8 ) 7 7 r e tr o sp e ct iv e 1 to 1 7 n r c t 1 .9 k h z r a d io lo g is t e f, a s ,t a n r 5 9 7 0 1 1 a s :a co u st ic sh a d o w in g ;e f :e ch o g e n ic fo cu s; c t :c o m p u te d to m o g ra p h y ;f n :f a ls e n e g a ti ve ;f p :f a ls e p o si ti ve ;n r :n o t re p o rt e d ; t a :t w in k li n g a rt if a ct ;t n :t ru e n e g a ti ve ;t p :t ru e p o si ti ve ;u s :u lt ra so n o g ra p h y. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e66 table 2: risk of bias of in included studies based on quality assessment of diagnostic accuracy studies 2 (quadas-2) recommendations study risk of bias applicability patient selection index test reference standard flow and timing patient selection index test reference standard hu, 2010 © © © © © © © johnson, 2011 § © © a © © © palmer, 2005 § © © a © © © passerotti, 2009 © © © © © © © roberson, 2018 § © © © © © © smith, 2000 § © a a © © © verhagen, 2019 § © © © © © © ©: low risk of bias; §: high risk of bias; a: unclear risk of bias table 3: subgroup analysis for assessment of ultrasonography in detection of renal calculi variable number of studies sensitivity (95% ci) p specificity (95% ci) p overall 7 0.80 (0.70 to 0.87) — 1.0 (0.84 to 1.0) — study design retrospective 5 0.80 (0.70 to 0.87) — 1.0 (0.75 to 1.0) — prospective 2 na — na operator radiologist/pediatric sonographer 4 0.76 (0.68 to 0.83) 0.14 1.0 (0.86 to 1.0) <0.0001 not reported 3 0.85 (0.75 to 0.96) 1.0 (1.0 to 1.0) reporting of us criteria no 4 0.82 (0.72 to 0.93) 0.09 1.0 (1.0 to 1.0) <0.0001 yes 3 0.77 (0.65 to 0.90) 0.99 (0.95 to 1.0) study year before 2010 4 0.78 (0.66 to 0.89) 0.33 1.0 (1.0 to 1.0) <0.0001 after 2010 3 0.82 (0.72 to 0.89) 1.0 (0.93 to 1.0) ci: confidence interval; na: not applicable as there is not enough studies in the category; us: ultrasonography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 8 appendix 1: table s1: search query of pubmed search terms 1. "ultrasonography"[mh] or ultrasonography[tiab] or echography[tiab] or doptone[tiab] or duplex echography[tiab] or echogram[tiab] or echoscopy[tiab] or echosound[tiab] or high resolution echography[tiab] or scanning, ultrasonic[tiab] or sonogram[tiab] or sonography[tiab] or ultrasonic detection[tiab] or ultrasonic diagnosis[tiab] or ultrasonic echo[tiab] or ultrasonic examination[tiab] or ultrasonic scanning[tiab] or ultrasonic scintillation[tiab] or ultrasonography[tiab] or ultrasound diagnosis[tiab] or ultrasound scanning[tiab] or ultrasound imaging[tiab] or imaging, ultrasound[tiab] or imagings, ultrasound[tiab] or ultrasound imagings[tiab] or ultrasonic imaging[tiab] or imaging, ultrasonic[tiab] or sonography, medical[tiab] or medical sonography[tiab] or diagnostic ultrasound[tiab] or diagnostic ultrasounds[tiab] or ultrasound, diagnostic[tiab] or ultrasounds, diagnostic[tiab] or echotomography[tiab] or diagnosis, ultrasonic[tiab] or diagnoses, ultrasonic[tiab] or ultrasonic diagnoses[tiab] or ultrasonic diagnosis[tiab] or echotomography, computer[tiab] or computer echotomography[tiab] or tomography, ultrasonic[tiab] or ultrasonic tomography[tiab] 2. "calculi"[mh] or "urinary calculi"[mh] or "urolithiasis"[mh] or "ureterolithiasis"[mh] or "ureteral calculi"[mh] or "kidney calculi"[mh] or "urinary bladder calculi"[mh] or calculi[tiab] or urinary calculi[tiab] or urolithiasis[tiab] or ureterolithiasis[tiab] or ureteral calculi[tiab] or kidney calculi[tiab] or urinary bladder calculi[tiab] or calculus[tiab] or urinary stones[tiab] or calculi, urinary[tiab] or calculus, urinary[tiab] or urinary calculus[tiab] or urinary stones[tiab] or stone, urinary[tiab] or stones, urinary[tiab] or urinary stone[tiab] or urinary tract stones[tiab] or stone, urinary tract[tiab] or stones, urinary tract[tiab] or urinary tract stone[tiab] or urinary lithiasis[tiab] or lithiasis, urinary[tiab] or ureterolithiases[tiab] or calculi, ureteral[tiab] or calculus, ureteral[tiab] or ureteral calculus[tiab] or calculi, kidney[tiab] or calculus, kidney[tiab] or kidney calculus[tiab] or nephrolith[tiab] or renal calculus[tiab] or renal calculi[tiab] or kidney stone[tiab] or stone, kidney[tiab] or stones, kidney[tiab] or renal calculi[tiab] or calculi, renal[tiab] or calculus, renal[tiab] or ladder calculi, urinary[tiab] or bladder calculus, urinary[tiab] or calculi, urinary bladder[tiab] or calculus, urinary bladder[tiab] or urinary bladder calculus[tiab] or bladder stones[tiab] or bladder stone[tiab] or stone, bladder[tiab] or stones, bladder[tiab] or calculi of urinary bladder[tiab] or urinary bladder stones[tiab] or bladder stone, urinary[tiab] or bladder stones, urinary[tiab] or stone, urinary bladder[tiab] or stones, urinary bladder[tiab] or urinary bladder stone[tiab] or vesical calculi[tiab] or calculi, vesical[tiab] or calculus, vesical[tiab] or vesical calculus[tiab] or bladder calculi[tiab] or bladder calculus[tiab] or calculi, bladder[tiab] or calculus, bladder[tiab] or cystoliths[tiab] or cystolith[tiab] or nephrolithiasis[tiab] or calculosis, kidney[tiab] or calculus, kidney[tiab] or familial nephrolithiasis[tiab] or kidney calculi[tiab] or kidney calculosis[tiab] or kidney calculus[tiab] or kidney calix stone[tiab] or kidney calyx stone[tiab] or kidney lithiasis[tiab] or kidney pelvis stone[tiab] or kidney stone[tiab] or kidney stone passage[tiab] or kidney stone, pelvis[tiab] or renal calculi[tiab] or nephrolith[tiab] or nephrolith passage[tiab] or renal calculus[tiab] or renal lithiasis[tiab] or renal pelvis stone[tiab] or renal stone[tiab] or renolithiasis[tiab] or stone, kidney[tiab] or coral stone[tiab] or stone, urinary tract[tiab] or stone, urine[tiab] or urinary calculi[tiab] or urinary calculus[tiab] or urinary stone[tiab] or urinary tract calculus[tiab] or urinary tract stone[tiab] or urine calculus[tiab] or urine stone[tiab] or urolith[tiab] or urolyt[tiab] or bladder calculi[tiab] or bladder calculosis[tiab] or bladder calculus[tiab] or bladder concrement[tiab] or bladder concretion[tiab] or bladder lithiasis[tiab] or bladder neck calculus[tiab] or bladder stone disease[tiab] or bladder stones[tiab] or calculosis, bladder[tiab] or calculus, urinary bladder[tiab] or cystolithiasis, urinary[tiab] or stone, bladder[tiab] or urinary bladder calculi[tiab] or urinary bladder stone[tiab] or urinary bladder stones[tiab] or vesical calculi[tiab] or vesical calculus[tiab] or vesical stone[tiab] or vesical stones[tiab] 3. "child"[mh] or "infant"[mh] or "infant, newborn"[mh] or "adolescent"[mh] or "pediatrics"[mh] or children[tiab] or infants, newborn[tiab] or newborn infant[tiab] or newborn infants[tiab] or newborns[tiab] or newborn[tiab] or neonate[tiab] or neonates[tiab] or adolescents[tiab] or adolescence[tiab] or teens[tiab] or teen[tiab] or teenagers[tiab] or teenager[tiab] or youth[tiab] or youths[tiab] 4. #1 and #2 and #3 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2019; 7 (1): e66 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flow diagram of the present meta-analysis figure 2: publication bias (a) and risk of bias (b) among included studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 10 figure 3: summary receiver operating characteristic (sroc) curve of ultrasonography in detection of renal calculi in children. auc: area under the curve; sens: sensitivity; spec: specificity figure 4: sensitivity and specificity of ultrasonography in detection of renal calculi in children. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2019; 7 (1): e66 figure 5: diagnostic score and diagnostic odds ratio of ultrasonography in detection of renal calculi in children. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: results: discussion conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 115 emergency (2014); 2 (3): 115-120 original research a retrospective analysis of the burn injury patients records in the emergency department, an epidemiologic study nilgün aksoy1*, senay arli2, ozlem yigit3 1. department of surgical nursing, faculty of nursing, akdeniz university, antalya, turkey 2. institute of neurological sciences, marmara university, istanbul, turkey 3. department of emergency medicine, akdeniz university, antalya, turkey abstract introduction: burns can be very destructive, and severely endanger the health and lives of humans. it maybe cause disability and even psychological trauma in individuals. . such an event can also lead to economic burden on victim’s families and society. the aim of our study is to evaluate epidemiology and outcome of burn patients referring to emergency department. methods: this is a cross-sectional study was conducted by evaluation of patients’ files and forensic reports of burned patients’ referred to the emergency department (ed) of akdeniz hospital, turkey, 2008. demographic data, the season, place, reason, anatomical sites, total body surface area, degrees, proceeding treatment, and admission time were recorded. multinomial logistic regression was used to compare frequencies’ differences among single categorized variables. stepwise logistic regression was applied to develop a predictive model for hospitalization. p<0.05 was defined as a significant level. results: two hundred thirty patients were enrolled (53.9% female). the mean of patients' ages was 25.3 ± 22.3 years. the most prevalence of burn were in the 0-6 age group and most of which was hot liquid scalding (71.3%). the most affected parts of the body were the left and right upper extremities. with increasing the severity of triage level (or=2.2; 95% ci: 1.024.66; p=0.046), intentional burn (or=4.7; 95% ci: 1.03-21.8; p=0.047), referring from other hospitals or clinics (or=3.4; 95% ci: 1.7-6.6; p=0.001), and percentage of burn (or=18.1; 95% ci: 5.42-62.6; p<0.001) were independent predictive factor for hospitalization. in addition, odds of hospitalization was lower in patients older than 15 years (or=0.7; 95% ci: 0.5-0.91; p=0.035). conclusion: this study revealed the most frequent burns are encountered in the age group of 0-6 years, percentage of <10%, second degree, upper extremities, indoor, and scalding from hot liquids. increasing esi severity, intentional burn, referring from other hospitals or clinics, and the percentage of burn were independent predictive factors for hospitalization. key words: emergency service; emergency room nursing; burns; hospital records cite this article as: aksoy n, arli s, yigit o. a retrospective analysis of the burn injury patients records in the emergency department, an epidemiologic study. emergency. 2014;2(3):115-20. introduction:1 urns can be very destructive, and severely endanger the health and lives of humans. it maybe cause disability and even psychological trauma in individuals. such an event can also lead to economic burden on victim’s families and society (1). a vast majority (95%) of burn-related deaths occur in developing countries. fire-related burns itself cause more than 300,000 deaths annually, in addition to a number of mortalities caused by scalding, electric burns, chemical burns or other types of burns (2). like other types of trauma, children and elders have an increased frequency of burn incidents and mortality (3, 4). in developed countries, close to 90% of burning cases occur because *corresponding author: nilgün aksoy; department of surgical nursing, faculty of nursing, akdeniz university, antalya, turkey. tel: +90 242 310 69 19; fax: +90 242 226 14 69 email: nilgunmutluaksoy@akdeniz.edu.tr received: june 2014; accepted: july 2014 of preventable incidents. different training programs for all groups of the society, intended to prevent burns, are available (5). since a national database regarding burn epidemiology is not available in turkey, therefore obtaining definitive data about the risk factors and burns’ distribution is not possible in this country. current national data on burns are either case reports belonged to various centers or regional outcomes based on descriptive studies (3). in turkey, the data of the frequency, causes, and risk factors affect mortality should be collected, analyzed, and interpreted. thus, measures especially for preventable types of burns should be planned. it has been observed that information contained in patient records is either not filled properly or at all, due to various causes such as shortage of health personnel, the sheer number of patients, serious illness, or trauma situations to which the intervention must be done quickly and health care providers’ experience negligence or unawareness of reporting b mailto:nilgunmutluaksoy@akdeniz.edu.tr this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com aksoy et al 116 (6). the aim of our study is to evaluate epidemiology and outcome of burn patients referring to emergency department. methods: study design and setting this is a cross-sectional study, which was conducted by retrospective evaluation of registration data from burned patients for any reason and entered to the emergency department (ed) of akdeniz university hospital from january to december 2008. this study was conducted with the consent of the related department and approved by local ethics committee. participants this was a retrospective study which all burn patients (242 cases), referred to the ed of akdeniz hospital during the study period were evaluated. the incomplete patients’ files were excluded (12 cases). finally, the data of 230 patients were entered to the study. based on 65.7% hospitalization of burn patients (7), with considering α=0.05, and d=0.1, 84 patients were calculated as the minimum sample size. data collection the data was collected from patients’ files, forensic reports, and computerized records. age, gender, the season, place (the location burn occurred), and reason of the burns, the anatomical sites of the burns, total body surface area and degrees of the burns, proceedings before and during hospitalization, and admission time were recorded. for calculation of the burn degree, the higher available value was used. causes of burns were analyzed into five main groups include hot liquid (water, milk, tea, soup, etc.), flame, electrical, chemical, contact with hot objects, and chemical. burn sites in patients were anatomically classified as head and neck, anterior trunk, posterior trunk, right and left upper extremity, right and left lower extremity, and genital. patients were divided as those discharged from hospital, hospitalized, dispatched to other ward, and rejected treatment. the triage level was assessed based on emergency severity index version iv (esi). the percentage of burn was calculated based on rule of nines (8). statistical analysis the obtained data was recorded and analyzed using spss version 21.0. quantitative data were presented as mean ± standard deviation, while qualitative data as frequencies and percentages. multinomial logistic regression was used to compare frequencies’ differences among single categorized variables. stepwise logistic regression was applied to develop a predictive model for hospitalization. p<0.05 was defined as a significant level. results: findings of the retrospective evaluation showed that of 230 patients admitted to ed with burns, 124 (53.9%) of table 1: distribution of characteristics of burns of patients (n = 230) variable n (%) gender female 124 (53.9) male 106 (46.1) age 0-6 81 (35.2) 7-14 5 (2.2) 15-24 34 (14.8) 25-34 31 (13.5) 35-44 23 (10.0) 45-54 21 (9.1) 55-64 23 (10.0) 65 and over 12 (5.2) the season of burn spring 57 (24.8) summer 71 (30.9) autumn 59 (30.9) winter 43 (30.9) burn that place home 190 (82.6) outdoor 17 (7.4) business location 15 (6.5) car 3 (1.3) unspecified 5 (2.2) application received first 30 minutes 86 (37.4) the first 31 to 60 minutes 54 (23.5) the first 61 to 120 minutes 15 (6.5) the first two hours and more 75 (32.6) burn reason scalding 164 (71.3 flame 18 (7.8) electricity 6 (2.6) come into contact with hot 31 (13.5) sunburn 3 (1.3) chemical substance 7 (3.0) due to friction 1 (0.4) percentage of burn less than 10% 175 (76.1) from 10 to 19% 18 (7.8) 20-29% 8 (3.5) 30-39% 4 (1.7) 40-49% arsine 1 (0.4) between 50-59% 3 (1.3) unspecified 121 (52.6) degree of burn 1 degree 56 (24.3 2 degree 110 (47.8) 3 degree 2 (0.9) 1 and 2 degree 46 (20.0) 2 and 3 degree 5 (2.2) 1, 2, 3 degree 2 (0.9) unspecified 9 (3.9) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 117 emergency (2014); 2 (3): 115-120 them were women and 106 (46.1%) men. patients' ages ranged between 0-86 years and the average of age was 5.3 ± 22.3 years. table 1 is summarized the background information of the studied subjects. when patients were analyzed according to age group, it was determined that most of them were in the 0-6 age group with 81 cases (35.2%). multinomial logistic regression showed a significant difference among burn prevalence in age groups (p<0.0001). based on this analysis, the prevalence of burn was significantly higher in ages under 7 years. noticing to burn dates, the most admissions were in july with 13.9% (n=32) and the less in december with 4.8% (n=10) (p<0.001). one hundred ninety (82.6%) cases of burns occurred at home, 17 (7.4%) outdoors, 15 (6.5%) workplace, 3 (1.3%) inside a vehicle, and 5 (2.2%) unclear (p<0.001) (figure 1). the most common cause of burns was hot liquid scalding, 71.3% (n=164), followed by contact with hot object 15.2% (n=35) (p<0.001). the most frequent percent and degree of burn were <10% (76.0%; p<0.001) and second-degree (67.8%; p<0.001), respectively. figure 2 presents causes of burn in different age groups. as it can be seen, burn with boiling water is the most common reason of burn except the ages of 7-14 years. also, in ages over 64 this is the only cause of burn. the most affected parts of the body are the left (n=70) and right upper extremities (n=64), while the least affected are genital (n=4) (p<0.001) (figure 3). the majority of patients (70.9%) did not apply any treatment for their burns while at home. two hundred thirteen cases (92.6%) were treated and dressed in the ed. while 79.6% of patients were discharged from the ed, 17.8% of them hospitalized. the length of hospitalization for 13% of the patients was 9 days or less (table 2). multivariate logistic regression demonstrated that with increasing the severity of esi (or=2.2; 95% ci: 1.02-4.66; p=0.046), intentional burn (or=4.7; 95% ci: 1.03-21.8; p=0.047), referring from other hospitals or clinics (or=3.4; 95% ci: 1.7-6.6; p=0.001), and percentage of burn (or=18.1; 95% ci: 5.42-62.6; p<0.001) were intable 2: distribution of the applications for burns (n = 230)  variable n (%) first respond after burns applying water 22 (9.6) applying ice 16 (7.0) applying toothpaste, tomato sauce, detergent and shoe polish 6 (2.6) applying bepanthen or aloe vera 23 (10.0) no application 163 (70.9) treatment and applications in hospital debridement and graft applied 11 (4.8) medical dressing and treatment 219 (95.2) disposition discharged 183 (79.6) hospitalizing in plastic and reconstructive surgery department 30 (13.0) hospitalizing in reanimation unit 8 (3.5) hospitalizing in eye department 3 (1.3) referring to another healthcare organization 4 (1.7) abandoning the emergency service 1 (0.4) refusing the treatment 1 (0.4) hospitalization duration hospitalization duration between 1-9 days 30 (13.0) hospitalization duration between 10-19 days 5 (2.2) hospitalization duration between 20-29 days 2 (0.9) hospitalization duration between 30 days and over 4 (1.7) not hospitalized 189 (82.2) table 3: independent risk factors for burn related hospitalization  variable odd ratio 95% confidence interval p increasing severity of esi 2.2 1.02-4.66 0.046 intentional burn 4.7 1.03-21.8 0.047 refer from other hospital or clinics 3.4 1.70-6.60 0.001 percentage of burn 18.1 5.42-62.6 <0.001 age over 15 years 0.7 0.50-0.91 0.035 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com aksoy et al 118 dependent predictive factor for hospitalization. in addition, odds of hospitalization was lower in patients older than 15 years (or=0.7; 95% ci: 0.5-0.91; p=0.035) (table 3). discussion: this study revealed that the most burn incidents occur in the 0-6 year’s age group and are a result of scalding. both upper extremities were affected more frequently than other regions. domestic burns are most common location of burn and second-degree burns encountered more frequently. in addition, increasing the severity of esi, intentional burn, referring from other hospital or clinics, and the percentage of burn were independent predictive factors for hospitalization. odds of hospitalization was lower in patients older than 15 years. panjeshahin et al. (9), saadat et al. (10) and several other studies found that burn injuries were more common in females (11). while, duzgun et al. (12) were determined that 61.7% and 54.8% of the patients were male. in this study it was seen that males less than woman were exposed to burns at a rate of 0.9:1. because women spend more time at home than men, they are more exposed to home accidents and especially higher incidence of burns. study conducted by kocaturk et al. (13) revealed that the mean age of burn experiencing was 21.3 years, while gunay et al. (14) showed it as 22 years old. additionally, more than half of these cases occurred in individuals under 14 years of age. anlatıcı et al. (15) declared that burns happened in patients of 0-4 years old at a rate of 28% and haberal et al. (16) demonstrated that the children constituted 56.7% of all patients experienced burns. the result of this study showed the higher incidence of burn among patients in 0-6 years’ age group. the incidence of burn in summer was highly prevalent in this study unlike other reviews (17, 18). chien et al.(17) and dedovic et al. (18) stated that spring is the most common season to experience a burn and sarıtas et al. (19) displayed that the majority of patients were admitted in winter (16%) and in the spring (30.7%). it was suggested that the rate of burn cases increase in antalya during summer because of the fact that people spend more time at home because of the high temperature and summer holidays. home was the most frequent place of burn followed by outdoor, workplace, and inside of a vehicle. a literature review showed that the majority of burn cases occur indoors in developing countries similar to our study (20, 21). the arrival time to the hospital were observed 67.4% within 2 hours and 32.6% after 2 hours. similarly, cöl et al. (22) reported that 85.7% of burn patients referred to ed within the first 2 hours of the event. santas et al. (19) stated that while 67% of the patients were discharged from ed after the first inter figure 1: cause of burn based on place  figure 2: the causes of burn based on age groups  figure 3: distribution of patients according to the affected anatomical localizations  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 119 emergency (2014); 2 (3): 115-120 vention, 16% of them hospitalized similar to the values in the present project. the most common cause of burns was scalding which was lined with some other studies (14, 23-26), although some reviews presented that other causes such as flame are more common (9, 11).this discrepancy may be due to the differences in burned population, jobs, and cultures. in addition, the three most common burn sites included the left and right upper extremity, and head and neck similar to other studies (22, 27). the literatures stated that since persons experienced the burn trauma usually use his hands as a reflex to protect themselves, the most frequently burned sites of patients are hands, arms, face, and legs (28). al et al. stated that 69.6% of patients applied cold water, burn ointment, or medical treatment, whereas 60.4% of them either did not apply the first aids or used it incorrectly (29). in the present project, because the majority of the patients (66.4%) referred to the ed within the first two hours, the number of patients who did not perform any medication was quite high. alcohol, drug intoxication (30), sex, inhalation injury, total body, surface area of burn, and total body surface area of burn were suggested in the several studies as hospitalization predictive factors (31). it was demonstrated that in addition to total body surface area (percentage of burn), age, increasing esi severity, intentional burns, and referring from other hospitals or clinics were independent predictive values of hospitalization. this study had some limitations; it was conducted retrospectively, only in one center and with small sample size. conclusion: this study revealed the most frequent burns are encountered in the age group of 0-6 years, percentage of <10%, second degree, upper extremities, indoor, and scalding from hot liquids. increasing esi severity, intentional burn, referring from other hospitals or clinics, and the percentage of burn were independent predictive factors for hospitalization. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department of akdeniz university hospital of antalya, turkey. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. edelman ls. social and economic factors associated with the risk of burn injury. burns. 2007;33(8):958-65. 2. peck m, molnar j, swart d. a global plan for burn prevention and care. bull world health organ. 2009;87(10):802-3. 3. simsek me, özgenel gy, kahveci r, akin s, özbek s, tufan f. outcomes of elderly burn patients requiring hospitalization. aging male. 2014 (0):1-3. 4. zayakova y, vajarov i, stanev a, nenkova n, hristov h. epidemiological analysis of burn patients in east bulgaria. burns. 2014;40(4):683-8. 5. liao c-c, rossignol am. landmarks in burn prevention. burns. 2000;26(5):422-34. 6. kutlu l, turasoy s, koşar n, ökdemir p. a retrospective evaluation of the medical records of burn patients presenting at the emergency polyclinic of a university hospital. j edu res nursing. 2006;3(2):40-4. 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[turkish]. 20. demirel y, col c, ozen m. evaluation of the patients treated in the ankara numune hospital burn centre in one year. cumhuriyet med j. 2001;23 (1):15-20. 21. guzel a, soyoral l, oncu mr, cakır c. analysis of patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com aksoy et al 120 who were admitted to burn unit and operated. van med j. 2012;19 (1):1-7. 22. çol m, çol c, afsar zo, d ç. an epidemiological analysis of burned cases admitted by ankara numune hospital. health soc assist found j. 1994;4(2):22-3. 23. wasiak j, spinks a, ashby k, clapperton a, cleland h, gabbe b. the epidemiology of burn injuries in an australian setting, 2000–2006. burns. 2009;35(8):1124-32. 24. song c, chua a. epidemiology of burn injuries in singapore from 1997 to 2003. burns. 2005;31(1):s18-s26. 25. ansari-lari m, askarian m. epidemiology of burns presenting to an emergency department in shiraz, south iran. burns. 2003;29(6):579-81. 26. kurtoŭlu m, alimoğlu o, ertekin c, güloğlu r, taviloğlu k. evaluation of severe burns managed in intensive care unit. ulusal travma ve acil cerrahi dergisi= turkish journal of trauma & emergency surgery: tjtes. 2003;9(1):34-6. [turkish]. 27. han th, kim jh, yang ms, et al. a retrospective analysis of 19,157 burns patients: 18-year experience from hallym burn center in seoul, korea. burns. 2005;31(4):465-70. 28. erkuran mk, ceylan a, düzenli e, büyükcam f. burn cases that are hospitalized in sanlıurfa education & research hospital. abant med j. 2013;2(2):123-9. 29. al b, gullu mn, okur h, ozturk h, kara i̇h, aldemir m. the epidemiology of scald and flame burns in east and south anatolia regions. j med invest. 2005;3(1):14-21. 30. grobmyer s, maniscalco s, purdue g, hunt j. alcohol, drug intoxication, or both at the time of burn injury as a predictor of complications and mortality in hospitalized patients with burns. j burn care res. 1996;17(6):532-9. 31. burd a. outcome analysis of 286 severely burned patients: retrospective study. hong kong med j. 2002;8(4):235-9. archives of academic emergency medicine. 2019; 7 (1): e23 le t t e r to ed i to r comment on “pregnancy screening before diagnostic radiography in emergency department; an educational review” harmen bijwaard1,2∗, fleur wit1 1. medical technology research group, inholland university of applied sciences, haarlem, the netherlands. 2. centre for safety, national institute for public health and the environment, bilthoven, the netherlands. received: february 2019; accepted: march 2019; published online: 6 april 2019 cite this article as: bijwaard h, wit f. comment on “pregnancy screening before diagnostic radiography in emergency department; an educational review”. arch acad emerg med. 2019; 7(1): e23. with great interest we have read the paper “pregnancy screening before diagnostic radiography in emergency department; an educational review” by a.i. abushouk et al. (1). we agree with the authors that unnecessary fetal radiation exposure should be avoided and that pregnancy screening can be a means to accomplish this. however, in their paper the authors suggest in several instances that radiological imaging during pregnancy can lead to teratogenic effects. in the abstract it is stated: “radiation exposure during pregnancy may have serious teratogenic effects to the fetus. therefore, checking the pregnancy status before imaging women of child bearing age can protect against these effects.”, and in the introduction: “therefore, checking the pregnancy status before imaging women of child bearing age can protect against radiation teratogenic effects.” we strongly disagree with these statements: common radiological imaging will usually not give rise to fetal radiation doses high enough to lead to teratogenesis. the statements in the paper may lead to unnecessary worrying of pregnant women and it may discourage them from undergoing medically necessary radiological examinations. “teratogenesis” comes from the greek words for “monster” and “producing”. it is used to describe the induction of malformations in the fetus by toxic agents. according to the international commission on radiological protection (icrp, 2000) such malformations may occur after exposure of the fetus to a radiation dose of at least 0.1 gy or more (2). however, in many cases the fetus will receive hardly any irradiation from a radiological examination. this is the case when ∗corresponding author: harmen bijwaard; bijdorplaan 15, 2015 ce, haarlem, the netherlands email: harmen.bijwaard@inholland.nl phone: +31 6 81410343 the fetus is outside the x-ray beam, for example during a ctscan of the brain of the mother. in the potentially worst cases the fetus is located directly in the x-ray beam, such as during pelvic examinations. a pelvic x-ray will usually lead to a radiation dose to the fetus of approximately 0.001 gy and a pelvic ct-scan may lead to a fetal radiation dose of 0.025 gy (icrp, 2000). slightly higher numbers are also quoted by abushouk et al. who write: “the usual radiation dose, delivered during plain x-ray imaging, is usually less than 0.02 gy (2 rad), while it rises to 0.02-0.035gy (2-3.5 rad) during computed tomography (ct). based on these calculations, even repeated abdominal or pelvic ct imaging should pose no theoretical risk to the fetus.” however, they continue with the following statement: “however, the national council on radiation protection and measurements stated a principle entitled “as low as reasonably achievable” or “alara” which highlighted that no radiation exposure level is entirely free of risk and that the safety of the procedure should be evaluated in terms of beneïňąt versus risk. in 2006, the national academy of sciences issued a report which highlighted the link between low levels of radiation exposure and the risk of teratogenesis and cancer induction.” this statement again suggests that there exists a link between low levels of radiation exposure and the risk of teratogenesis, where in fact there is only a link between these low exposures and a slightly increased risk of cancer induction. common radiological procedures will not lead to teratogenesis. this may only occur in the very rare case that very many (pelvic) radiological procedures are carried out or when either radiotherapy or an extensive interventional radiological procedure is carried out during which the fetus is located in the x-ray beam. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. bijwaard et al. 2 1. appendix 1.1. acknowledgements none. 1.2. author’s contribution both authors contributed to the text of this comment. 1.3. conflict of interest none. 1.4. funding and support this research has been co-financed by the taskforce for applied research (sia), which is part of the dutch national science foundation (nwo). references 1. abushouk ai, taheri ms, pooransari p, mirbaha s, rouhipour a, baratloo aje. pregnancy screening before diagnostic radiography in emergency department; an educational review. 2017;5(1):e60. 2. valentin jjai. pregnancy and medical radiation: icrp publication 84. 2000;30(1):1-43. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references archives of academic emergency medicine. 2019; 7 (1): e20 or i g i n a l re s e a rc h the most and least stressful prehospital emergencies from emergency medical technicians’ view point; a crosssectional study afshin khazaei1, maryam esmaeili2∗, elham navab2 1. intensive care and management nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. critical care and geriatric nursing department, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. received: november 2018; accepted: december 2018; published online: 15 february 2019 abstract: introduction: exposure to different prehospital emergencies (pe) may have a different impact on emergency medical technicians (emts) based on the characteristics and circumstances of the emergency. the present study aimed to prioritize pe types according to their stressfulness as well as their correlation with post traumatic stress disorders (ptsd). methods: in this cross-sectional study, all emts in the emergency medical services (ems) of hamadan province were invited to participate, voluntarily. the study questionnaire comprised of two parts: a) personal characteristics and prioritizing pe types in terms of their stressfulness and b) the ptsd checklist. kruskal-wallis test was used for examining the relationship between total ptsd score and the most and the least stressful pes. multivariate logistic regression was also used to predict the impact of different types of pes on ptsd. results: 259 emts with the mean age of 32.79±6.16 years were studied. the total mean score of ptsd on pcl-5 was 21.60±11.45. also, 20.1% of technicians met the criteria for ptsd. the mean age of technicians who met ptsd criteria was less than that of technicians who did not meet ptsd criteria (28 vs. 33 years, p<0.001). the most and least stressful emergencies were cardiovascular (24.7%) and environmental (26.3%) emergencies, respectively. there was a significant correlation between the most (kruskal-wallis=40.92, df=12, p<0.001) and the least stressful emergencies (kruskal-wallis=28.22, df=15, p = 0.02) from emts’ viewpoint and ptsd score. multivariate logistic analysis showed that gynecologic (aor=2.28, wald=5.83, p=0.016) and allergic (aor=0.12, wald=10.16, p=0.01) emergencies were significant predictive factors of ptsd. conclusion: based on the view point of the studied emts, cardiac and environmental emergencies were the most and least stressful emergencies. the frequency of ptsd in this series was about 20% and it significantly correlated with younger age, lower experience, higher number of shifts, non-official employment and emt degree. based on multivariate logistic analysis, gynecologic and allergic emergencies were the only significant predictive factors of ptsd. keywords: emergency medical services; emergency medical technicians; stress disorders, post-traumatic; mental disorders; emergency treatment cite this article as: khazaei a, esmaeili m, navab e. the most and least stressful prehospital emergencies from emergency medical technicians’ view point; a cross-sectional study. arch acad emerg med. 2019; 7(1): e20. 1. introduction emergency medical technicians (emts) experience significant stress at work (1). the cumulative stresses experienced can be associated with traumatic events and cause traumatic stresses (2). traumatic or critical events often refer to inci∗corresponding author: maryam esmaeili; school of nursing and midwifery, nosrat st. tohid sq. tehran, iran. 141973317. tel: 00989125786095 email: esmaeiliem@yahoo.com dents in which emts experience severe and acute stress in the face of situations like witnessing the death of patients (including children), feeling unable to help the patient and feeling at risk (3). frequent and repeated exposure to potentially traumatic events may expose emts to serious psychiatric compromise such as post-traumatic stress disorder (ptsd) (4, 5). ptsd is a complex physical, cognitive, emotional, behavioural and psychological disorder, which is associated with intrusive thoughts, nightmares, avoiding reminders of a trauma, anxiety, and sleep disturbance, which ultimately leads to social, occupational and interpersonal disorders (6). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. khazaei et al. 2 while efforts have been made to identify the critical or traumatic events in the prehospital setting, so far a comprehensive review of various types of the prehospital emergencies (pes) in term of their stressful situations has not been done and studies in this area are still sparse. donnelly et al., for example, identified 29 incidents that were considered traumatic events by technicians, such as seeing a death scene, seeing the scene where patients have been beaten, threatened with weapons, the scene where technicians have been threatened, exposure to toxic substances, and severe vehicle accidents (7). therefore, exposure to different pes may have a different impact on technicians based on the characteristics and circumstances of the emergency (unpredictable, non-controllable, and dynamic environment). for example, guise et al. showed in their study that pediatric emergencies would cause the most stress and anxiety in emts (8). bostrom et al. also introduced obstetric and gynecologic emergencies under uncertain prehospital conditions as the most stressful mission for emts (9). in iran, emergency missions for which emts are dispatched include cardiovascular, environmental, respiratory, shock, obstetric and gynecologic, neurological, toxicity, metabolic, burning, accidents, acute abdominal and bleeding emergencies (10, 11). one of the questions that are not yet comprehensively answered is that exposure to which type of pre-hospital emergency causes the most and least stress from the technicians’ perspective. with the current overall ptsd prevalence (from 11% to 35%) among emts (12, 13), which is the highest among rescue workers (including police or firefighters) (14), assessing the mental health of ems providers and identifying staff at high risk of developing ptsd is vital. also, identifying the order in which pe types associate with ptsd can be effective in development of practical approaches to reduce the stress among ems staff. therefore, the present study aimed to prioritize pe types according to their stressfulness as well as their correlation with post traumatic stress disordes (ptsd). 2. methods 2.1. study design and setting this study is a multicenter, cross-sectional study, conducted between july 2018 and october 2018. the study population comprised of emts in emergency bases in hamadan province (in west of iran) that has 20 metropolitan bases, 30 road bases, and one air base, which serve a population of about two million. all emts in the emergency medical services (ems) of hamadan province were invited to take part in our study, voluntarily. information about the study was orally given to the emts before its initiation. also, the participants were assured that their names and personal information would be kept confidential. the research project was approved by the ethical committee of the school of nursing and midwifery and school of rehabilitation of tehran university of medical sciences (no: ir.tums.fnm.rec.1397.042). 2.2. participants the total number of emts in hamadan at the time of data collection was 307. the active emts who were present in urban, road and air emergency bases on a full-time basis and announced their oral and written approvals were included in the study. non-active ems personnel, personnel from other medical centers working part time in the ems and the personnel who had experienced non-occupational stressors, such as the death of close relatives, etc. in the previous eight weeks were excluded from the study. 2.3. data gathering the study questionnaire comprised of two parts: a) personal characteristics and prioritizing pre-hospital emergency types in terms of their stressfulness and b) the ptsd checklist, which was a 20-item self-report measure that assessed the presence and severity of ptsd symptoms. items on the ptsd checklist for dsm-5 (pcl-5) correspond with dsm5 criteria for ptsd, which is intended to assess the individual’s symptoms in the past month (15). the pcl-5 checklist has 20-items divided into four clusters including; bintrusion (five items), c-avoidance (two items), d-negative alterations in cognition and mood (seven items) and ealterations in arousal and reactivity (six items). also, the items of the ptsd checklist are rated on a 5-point likert-type scale (0=”not at all” to 4=”extremely”). therefore, a total ptsd score can be obtained by summing up the scores of the 20 items (ranges from 0 to 80). also, ptsd diagnosis via a pcl-5 cut-point score, which is the score of 33, seems logical when further psychometric testing is not available (15-17). therefore, we divided ptsd scores into score≥33 (met the criteria for ptsd) and score<33 (did not meet the criteria for ptsd) for screening. the questionnaires were given to the participants by the researcher and collected after completion. technicians were asked to report the most and the least stressful prehospital emergencies from their point of view. reliability and validity of this checklist have been evaluated in several studies and most of these studies showed the high validity and reliability of this tool in detecting ptsd symptoms (1820). validity and reliability of the persian version of this tool were also tested through factor analysis and cronbach’s alpha (0.79%), as well as retest (0.77%), which were ultimately satisfactory (21). however, we reassessed the reliability of pcl-5 through cronbach’s α (0.89). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e20 figure 1: the frequency of participants’ votes to least and most stressful prehospital emergencies. 2.4. statistical analysis in a study conducted by sedigheh and et al. (22), ptsd rate reported in the emts was 0.22%. using this data and taking into account the relative errors of 5% and 95% confidence interval (ci), as well as applying the coefficient of the limited population (a total of 307 active emts); a minimum of 251 participants was required. means and standard deviations were used for reporting normally distributed continuous data. non-normally distributed variables were expressed as median (iqr). categorical variables were reported as frequency and percentages. kruskal-wallis test was used for examining the correlation between total ptsd score and the most and the least stressful prehospital emergencies. the multivariate logistic regression model was also used to predict the impact of different types of prehospital emergencies on ptsd. the forward selection (wald) method was used to select covariates for the adjusted models. a receiver operating characteristic (roc) curve was also drawn for the final adjusted model. all statistical analyses were performed using ibm spss statistics (v. 20). p<0.05 was considered significant (two-tailed). 3. results 3.1. baseline characteristics of studied emts 259 emts entered the study after being screened for the inclusion criteria. the mean age of participants was 32.79±6.16 years and their median work experience was 9 years (iqr: 512). the mean ptsd score on pcl-5 was 21.60±1.45. also, 20.1% of the technician met the criteria for ptsd. the mean age of technicians who met ptsd criteria was less than that of technicians who did not meet ptsd criteria (28 vs. 33 years, p<0.001). more details of demographic characteristics in terms of meeting ptsd criteria or not are shown in table 1. cardiovascular (24.7%), gynecological (22.0%) and pediatric (20.1%) emergencies, respectively, were most frequently introduced as the most stressful emergencies by the participants. also, the environmental (26.3%), behavioural (17.4%) and neurological (9.7%) emergencies were most frequently introduced as least stressful emergencies, respectively (figure 1). also, the technicians based in urban, road and air bases stated that the most stressful emergencies were cardiovascular (21.62%), gynecological (10.42%) and penetrating trauma (1.16%), respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. khazaei et al. 4 table 1: the relationship between demographic characteristics and meeting or not meeting ptsd criteria variable ptsd p no (score ≥ 33) yes (score < 33) age (year) 33.77 ± 5.56 28.88 (6.94) < 0.001 number of missions (iqr) 60 (6 85) 42 (12 110) 0.029 work experience (year) 9.71 ± 4.73 5.12 ± 4.31 < 0.001 number of shifts (iqr) 11 (10-12) 14 (13-15) < 0.001 ptsd (total score) 17.47±8.36 38.02±6.08 < 0.001 base location urban 136 (82.4) 29 (17.6) road 49 (71.0) 20 (29.0) 0.079 air 22 (88.0) 3 (12.0) marital status married 137 (80.1) 34 (19.9) single 67 (80.7) 16 (19.3) 0.529 divorced 3 (60.0) 2 (40.0) employment status official 85 (87.6) 12 (12.4) 0.017 non-official 122 (75.3) 40 (24.7) degree emt 96 (73.8) 34 (26.2) 0.038 operating room technician 27 (77.1) 8 (22.9) anesthesia technician 29 (87.9) 4 (12.1) nurse 55 (90.2) 6 (9.8) in-service training yes 112 (80.6) 27 (19.4) 0.778 no 95 (79.2) 25 (20.8) data are presented as mean ± standard deviation or number (%). iqr: interquartile range. table 2: the mean of ptsd cluster scores in more stressful and least stressful prehospital emergencies emergencies intrusion avoidance alterations in cognitions arousal & reactivity more stressful cardiovascular 5.67±3.22 2.61±1.85 8.44±5.12 7.75±4.14 gynecological 5.58±3.23 2.51±1.61 8.47±4.72 7.79±4.19 pediatric 5.31±3.07 2.33±1.59 8.02±4.14 7.62±3.89 least stressful environmental 4.32±2.33 1.97±1.45 6.71±3.88 5.97±3.44 behavioural 4.98±3.31 2.31±1.88 6.98±4.60 7.20±4.84 neurological 5.96±3.18 2.44±1.75 9.16±5.39 8.08±4.40 data are presented as mean ± standard deviation. 3.2. ptsd and stressfulness of emergencies there was a significant correlation between the most (kruskal-wallis=40.92, df=12, p<0.001) and the least stressful emergencies from the viewpoint of emts (kruskalwallis=28.22, df=15, p=0.02) and ptsd score. emts who were stationed at the urban bases were more at risk for ptsd. mean work experience in the ptsd and non-ptsd groups were 5.12±4.31 and 9.71±4.73 (p<0.001) (table 1). in terms of ptsd cluster symptoms, in the most and the least stressful pes, negative alterations in cognitions and intrusion were the higher and lower frequency of ptsd cluster symptoms, respectively (table 2). after controlling confounding factors, the multivariate logistic analysis showed that gynecologic (aor=2.28, wald=5.83, p=0.016) and allergic (aor=0.12, wald=10.16, p=0.01) emergencies were significant predictive factors of ptsd. 4. discussion based on the view point of the studied emts, cardiac and environmental emergencies were the most and least stressful emergencies. the frequency of ptsd in this series was around 20% and it significantly correlated with younger age, lower experience, higher number of shifts, non-official employment and emt degree. based on multivariate logistic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e20 analysis, gynecologic and allergic emergencies were the only factors that significantly correlated with ptsd. the level of ptsd among emts in our study (nearly 20%) was higher than other studies in this field. the results of a systematic review showed that ptsd prevalence rates among ambulance staff was about 11% (23). the results of our study indicated that younger people are more vulnerable when exposed to prehospital emergencies in comparison with older staff, which was inconsistent with other studies (24). our study showed that cardiac, gynecological and pediatric emergencies were the most stressful emergencies from the viewpoint of emts. in contrast, environmental, behavioural and neurological emergencies were the least stressful missions. in this regard, in a qualitative study, bohstrom et al. showed that going on missions that involved sick children and childbirth were considered as major stress factors by emts (9). in their study, bracken-scally et al. also stated that from the perspective of most retired emts, incidents involving children were particularly difficult to manage (25). also, in a qualitative study, froutan et al. showed that pre-hospital burn mission was a unique experience from the perspective of iranian emergency care staff (26). cardiac emergency is among the most challenging and frequent missions in the prehospital setting (27), which was selected as the most stressful mission by emts in our study. we do not know whether exposure to cardiovascular emergency affects the onset or progression of ptsd in the emts or not, but it has been proven that experiencing stressful events induces psychological and physiological stress reactions, which lead to mental disorders (28). additionally, compton et al. showed that witnessing unsuccessful out-ofhospital cardiopulmonary resuscitation (cpr) may be associated with displaying symptoms of ptsd in the layperson (24). work experience was another factor in our study that affected ptsd severity. in our study, mean work experience in ptsd group was lower than non-ptsd group. this result was in contradiction with the study of bezabh et al. that showed the odds of developing ptsd were more than two times higher among emts with 4-5 years of work experience compared to those with 3 years of work experience (aor=2.67;p<0.001)(29). one of the reasons that gynecological emergency is identified as a stressful mission in our study could be that in iran, emts do not participate in any practical training courses on real patients during their study in university and in-service periods and they receive this skill only in theoretical education or on a mannequin. it should be noted that in iran, only female health care providers can participate in gynecological practice while all the emts are male. also, technicians of road bases selected gynecological emergency as a stressful mission. this could be due to the long distances between road bases and medical centers and the probability of mortality and morbidity of the mothers and infants as a result of this delay, the stress of facing this type of emergency is more in the technicians based on road bases. however, carrying out a qualitative study in the pre-hospital emergency is necessary for identifying the various aspects of this issue. ems managers need to assess pes for anticipating the possible traumatic events that may affect the emts in order to develop appropriate strategies to deal with the negative mental effects on the staff at risk. therefore, there is a need to carry out more studies, especially a qualitative study, to uncover and provide a thorough description of potential stress in exposure to a variety of pes. 5. limitation because of the cumulative effect of stresses in exposure to pre-hospital emergencies and heterogeneity of traumatic events, the ptsd in the emts cannot be attributed to a special prehospital emergency. in other words, due to the cumulative effect of stress, it is not possible to determine the contribution of each of these emergencies to onset or development of ptsd in emts. the results of this study were obtained in our context using multivariate logistic regression after controlling for the possibility of other potentially influential pe and interaction between them. therefore, the results of this study may not be generalizable to other contexts. 6. conclusion based on the view point of the studied emts, cardiac and environmental emergencies were the most and least stressful emergencies. the frequency of ptsd in this series was stimated to be about 20% and this ratio was significantly higher in younger emts, those with lower experience, higher number of shifts, non-official employment and emt degree. based on multivariate logistic analysis, gynecologic and allergic emergencies were the only factors significantly correlating with ptsd. 7. appendix 7.1. acknowledgements special thanks to the director of the disaster and emergency management center of hamedan province for helping us perform the study. 7.2. author contribution elham navab, maryam esamaeili and afshin khazaei designed the study. abbas mogimbeigi analyzed the data and aided in interpreting the results. finally, all authors discussed the results and contributed to the final manuscript. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. khazaei et al. 6 authors’ orcids afshin khazaei: 0000-0002-8063-3419 maryam esmaeili: 0000-0002-4798-2270 elham navab: 0000-0002-5210-9070 7.3. funding/support this research was also part of a phd dissertation by tehran university of medical sciences (grant no: 9421199001). 7.4. conflict of interest the authors report no conflict of interest. the authors alone are responsible for the content and writing of the paper. references 1. halpern j, maunder rg, schwartz b, gurevich m. downtime after critical incidents in emergency medical technicians/paramedics. biomed research international. 2014;2014:483140. 2. kilic c, inci f. 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mental health. 2014;16(1):223-31. 26. froutan r, khankeh hr, fallahi m, ahmadi f, norouzi k. pre-hospital burn mission as a unique experience: a qualitative study. burns : journal of the international society for burn injuries. 2014;40(8):1805-12. 27. dyson k, bray je, smith k, bernard s, straney l, finn j. paramedic exposure to out-of-hospital cardiac arrest resuscitation is associated with patient survival. circulation cardiovascular quality and outcomes. 2016;9(2):154-60. 28. bisson ji, cosgrove s, lewis c, robert np. posttraumatic stress disorder. bmj (clinical research ed). 2015;351:h6161-h. 29. bezabh yh, abebe sm, fanta t, tadese a, tulu m. prevalence and associated factors of post-traumatic stress disorder among emergency responders of addis ababa fire and emergency control and prevention service authority, ethiopia: institution-based, cross-sectional study. bmj open. 2018;8(7):e020705-e. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 184 emergency (2016); 4 (4): 184-187 original article the accuracy of plain radiography in detection of traumatic intrathoracic injuries maryam abedi khorasgani1, ali shahrami1, majid shojaee1, hossein alimohammadi1, afshin amini1, hamid reza hatamabadi2* 1emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. *corresponding author: hamidreza hatamabadi, department of emergency medicine, imam hossein hospital, shahid madani avenue, tehran, iran. tel: +989123861683; email: hhatamabadi@yahoo.com. received: july 2015; accepted: september 2015 abstract introduction: rapid diagnosis of traumatic intrathoracic injuries leads to improvement in patient management. this study was designed to evaluate the diagnostic value of chest radiography (cxr) in comparison to chest computed tomography (ct) scan in diagnosis of traumatic intrathoracic injuries. methods: participants of this prospective diagnostic accuracy study included multiple trauma patients over 15 years old with stable vital admitted to emergency department (ed) during one year. the correlation of cxr and ct scan findings in diagnosis of traumatic intrathoracic injuries was evaluated using spss 20. screening characteristics of cxr were calculated with 95% ci. results: 353 patients with the mean age of 35.2 ± 15.8 were evaluated (78.8% male). age 16-30 years with 121 (34.2%), motorcycle riders with 104 (29.5%) cases and iss < 12 with 185 (52.4%) had the highest frequency among patients. generally, screening performance characteristics of chest in diagnosis of chest traumatic injuries were as follows: sensitivity 50.3 (95% ci: 44.8 – 55.5), specificity 98.9 (95% ci: 99.5 – 99.8), ppv 97.8 (95% ci: 91.5 – 99.6), npv 66.4 (95% ci: 60.2 – 72.03), plr 44.5 (95% ci: 11.3 175.3), and nlr 0.5 (95% ci: 0.4 – 0.6). accuracy of cxr in diagnosis of traumatic intrathoracic injuries was 74.5 (95% ci: 69.6 – 78.9) and its area under the roc curve was 74.6 (95% ci: 69.3 – 79.8). conclusion: the screening performance characteristics of cxr in diagnosis of traumatic intrathoracic injuries were higher than 90% in all pathologies except pneumothorax (50.3%). it seems that this matter has a great impact on the general screening characteristics of the test (74.3% accuracy and 50.3%sensitivity). it seems that, plain cxr should be used as an initial screening tool more carefully. keywords: x-rays; radiography, thoracic; tomography, x-ray computed; diagnostic techniques and procedures; thoracic injuries cite this article as: abedi khorasgani m, shahrami a, shojaee m, alimohammadi h, amini a, hatamabadi h. the accuracy of plain radiography in detection of traumatic intrathoracic injuries. emergency. 2016;4(4):184-187 introduction: rauma is considered one of the major causes of mortality and permanent disability and the 4th cause of death behind cardiovascular diseases, cancer, and stroke (1, 2). based on the statistics reported by the iranian legal medicine organization, trauma and its consequences are the most common cause of mortality in iran, as 75.9% and 74.1% of deaths were trauma related in 2003 and 2004, respectively (3). among injuries due to trauma, chest trauma is responsible for 25% of deaths due to trauma and 50% of trauma-related deaths (4, 5). diagnostic and treatment approaches may vary depending on the equipment of the center and the physician’s decision. physical examination and chest radiography (cxr) are the first steps in diagnosis and treatment of multiple trauma patients. accuracy of the diagnoses are widely dependent on the type of injury, time of arrival, and the method of diagnosis used (6). during the past decade, imaging diagnostic methods have improved and therefore, accuracy of pulmonary contusion, hemothorax, and pneumothorax diagnosis has increased. yet, these methods do not have high specificity in ruling out chest and abdominal injuries (6). chest computed tomography (ct) scan as the gold standard, can diagnose pulmonary contusion, hemothorax, pneumothorax, and rib fracture with high sensitivity (7). rapid diagnosis of pneumothorax in patients with traumatic injuries, has led to improvement in patient management. sensitivity of ct scan compared to cxr, is 100% compared to 42% in this regard (8-11). yet, cxr is t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 185 emergency (2016); 4 (4): 184-187 still considered a useful and non-expensive method providing valuable information in the initial evaluation of trauma patients (9, 12). considering global and national statistics on trauma, especially chest trauma and its high prevalence in the youth population, this study was designed to evaluate the diagnostic value of cxr in comparison to chest ct scan in diagnosis of traumatic intrathoracic injuries. methods: in the present prospective diagnostic accuracy study, the value of cxr for diagnosis of traumatic intrathoracic injuries was evaluated in comparison to ct scan. the participants of this study included multiple trauma patients admitted to emergency department (ed) of imam hossein hospital, tehran, iran, during march 2014 to february 2015. multiple trauma patients over 15 years old with stable vital signs and those who had requests for both plain cxr and ct scan of chest were enrolled. exclusion criteria consisted of unstable vital signs, penetrating trauma, pregnancy, and not undergoing cxr or chest ct scan. demographic data of the patients, trauma mechanism and severity of injury based on injury severity score (iss), and cxr and ct scan findings regarding presence of hemothorax, pneumothorax, pulmonary contusion, and fracture of rib, spine, and sternum were recorded in a checklist. finally, the correlation of cxr and ct scan findings in diagnosis of chest traumatic injuries was evaluated. physical examination, history, and data gathering for all patients was done by an emergency medicine resident in charge of trauma unit. since the accuracy of cxr interpretation has been proved to be high for emergency medicine specialists (13), interpretation of cxr was done by a senior emergency medicine resident who was blind to the patients’ clinical conditions. chest ct scans were also reported by a radiologist blind to the clinical condition of the patients. based on the helsinki declaration, patient data were kept confidential. none of the patients underwent cxr outside the treatment process and ct scan indications were determined based on the advanced trauma life support (atls) guidelines or the decision of in charge surgeon. chest ct scan was considered the gold standard. all cxrs were performed as posterior-anterior while the patient was in upright position. statistical analysis: sample size was calculated to be 87 cases considering 65% sensitivity of cxr in diagnosis of intrathoracic injuries, 10% desired precision, and 95% confidence interval (ci). spss 20 was used to analyze data. correlation of two studied imaging was calculated using spearman's rank correlation coefficient. quantitative variables were reported as mean and standard deviation (sd) and qualitative ones as frequency and percentage. sensitivity, specificity, positive and negative predictive value (ppv and npv) and positive and negative likelihood ratio (plr and nlr) of cxr in comparison with ct scan were calculated with 95% ci. finally, area under the receiver operating characteristic (roc) curve of cxr was calculated. results: 353 patients with the mean age of 35.2 ± 15.8 were evaltable 1: baseline characteristics of the studied patients variables frequency (%) age (years) 16-30 121 (34.28) 31-45 99 (28.05) 46-60 83 (23.51) > 61 50 (14.16) sex male 278 (78.8) female 75 (21.2) trauma mechanism car passenger 102 (28.9) motorcycle rider 104 (29.5) pedestrian 90 (25.5) bicycle rider 3 (0.8) car rollover 25 (7.1) crush 5 (1.4) falling from > 3m 24 (6.8) injury severity* < 12 185 (52.4) ≥ 12 168 (47.6) * based on injury severity score (iss). table 2: screening performance characteristics of chest x-ray in detection of traumatic intra-thoracic injuries characteristics type of injury (95% confidence interval) pneumothorax hemothorax contusion sensitivity 45 (32.1-58.4) 99 (97.2-99.8) 98.9 (96.8-99.8) specificity 98.6 (96.5-99.6) 29.8 (17.3-44.9) 7.59 (2.84-15.8) ppv1 89.8 (85.9-92.8) 90.2 (86.5-93.1) 88.8 (74.1-83) npv2 87.1 (70.2-96.4) 82.4 (56.6-96.2) 66.7 (29.9-92.5) plr3 1.7 (1.43-2.26) 1.4 (1.17-1.7) 1.07 (1-1.14) nlr4 0.03 (0.11-0.83) 0.03 (0.009-0.11) 0.14 (0.036-0.56) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com abedi khorasgani et al 186 uated (78.8% male). table 1 shows the baseline characteristics of the patients. age 16-30 years with 121 (34.2%), motorcycle riders with 104 (29.5%) cases and iss < 12 with 185 (52.4%) had the highest frequency among patients. there was a significant correlation between the findings of two studied modalities (ρ = 0.68; p < 0.001). screening characteristics of plain cxr in diagnosis of various traumatic intrathoracic injuries and fractures are presented in tables 2 and 3, respectively. generally, screening performance characteristics of chest in diagnosis of chest traumatic injuries were as follows: sensitivity 50.3 (95% ci: 44.8 – 55.5), specificity 98.9 (95% ci: 99.5 – 99.8), ppv 97.8 (95% ci: 91.5 – 99.6), npv 66.4 (95% ci: 60.2 – 72.03), plr 44.5 (95% ci: 11.3 175.3), and nlr 0.5 (95% ci: 0.4 – 0.6). accuracy of cxr in diagnosis of traumatic intrathoracic injuries was 74.5 (95% ci: 69.6 – 78.9) and its area under the roc curve was 74.6 (95% ci: 69.3 – 79.8) (figure 1). discussion: based on the findings of the present study, cxr has low sensitivity in diagnosing traumatic intrathoracic injuries compared to ct scan. while its specificity and plr is high and close to that of ct scan. carrying out physical examination and plain cxr are considered as the first step in diagnosing traumatic chest injuries. el wakeel et al. in the study of 100 blunt chest trauma patients showed the higher sensitivity of ct scan compared to cxr in detection of intrathoracic injuries (7). as shown in table 2 and 3, the screening characteristics of cxr are higher than 90% in all pathologies except pneumothorax. it seems that this matter has a great impact on the general screening characteristics of the test. the pneumothorax cases, which were missed with cxr and diagnosed by ct scan are frequent and named occult pneumothorax, which usually are benign in nature. in a study, eckstein et al. estimated the sensitivity of cxr to be 42% in diagnosis of pneumothorax (10). diagnosis of hemothorax in cxr is difficult due to different reasons such as: the patient not being able to sit up, poor quality of the radiography, and improper preparation before radiography (being in sitting or upright position for at least 15 minutes before radiography performance). in the present study, sensitivity and specificity of cxr in diagnosis of pulmonary contusion were estimated to be 98.9 and 7.59%, respectively. these measures were 40 and 100%, respectively in the eckstein study (10). chest ct scan as the gold standard can diagnose pulmonary contusion, hemothorax, pneumothorax, and rib fracture with high sensitivity (8-12). despite the efficiency and high diagnostic value of ct scan in trauma patients, few evidence based indications exist for using this method for all patients. therefore, using it as a routine screening method is still a matter of debate (10). chardoli et al. believed that use of chest ct scan as an initial screening tool in trauma patients with stable hemodynamics can change the patient management and outcome (14). although ct scan can be very useful for evaluation of chest trauma patients, especially those with lung parenchyma injuries, hemothorax, and pneumothorax, the nephrotoxicity due to contrast material, cumulative dose of radiation, and the high cost of ct scan are problems that cannot be overlooked (6). on the other hand, performing plain cxr and then ct scan to confirm the results doubles the problem. therefore, a decision on whether all chest trauma patients with stable hemodynamics should undergo ct scan from the start cannot be made yet. it seems that making a decision based on a combination of physical examination, history, trauma mechanism, as well as imaging can be very helpful in this table 3: screening performance characteristics of chest x-ray in detection of traumatic thoracic fractures characteristics type of fracture (95% confidence interval) rib sternal vertebral sensitivity 98.9 (3.3-20.7) 99.7 (98.4-100) 100 (98.9-100) specificity 57 (45.3-68.1) 40 (5.2-85.3) 22.7 (7.8-45.4) ppv1 88.9 (84.8-92.2) 99.1 (97.5-99.8) 95.1 (92.3-97.1) npv2 93.8 (82.8-98.7) 66.7 (9.4-99.2) 100 (47.8-100) plr3 2.3 (1.78-2.26) 1.6 (0.8-3.4) 1.29 (1.03-1.62) nlr4 0.019 (0.006-0.06) 0.007 (0-0.06) 0 (0-0) 1. positive predictive value; 2. negative predictive value; 3. positive likelihood ratio; 4. negative likelihood ratio. figure 1: receiver operating characteristics (roc) curve of chest x-ray in comparison with computed tomography scan 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n s it iv it y 0.00 0.25 0.50 0.75 1.00 1 specificity area under roc curve = 0.7457 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2016 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 187 emergency (2016); 4 (4): 184-187 regard. the new methods suggested for chest trauma evaluation, tend to use scoring systems and clinical decision rules to some extent (15, 16). it seems that routine use of cxr based on atls protocol for all multiple trauma patients is questionable. in this regard, new clinical decision rules similar to nexus (16) and tirc (15) that have been designed for clinical triage of patients in need for chest imaging, can be implemented after validation studies. conclusion: based on the findings of the present study, the screening performance characteristics of cxr in diagnosis of traumatic intrathoracic injuries were higher than 90% in all pathologies except pneumothorax. it seems that this matter has a great impact on the general screening characteristics of the test (74.3% accuracy and 50.3%sensitivity). it seems that, plain cxr should be used as an initial screening tool for all the chest trauma patients more carefully. acknowledgment: the authors would like to thank all the staff of trauma unit of imam hossein hospital that helped carry out this study. this article is extracted from the thesis of dr. abedi khorasgani to earn her specialist degree in emergency medicine, registered under the number 312 in the research and technology department of shahid beheshti university of medical sciences. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. khaji a, ghodsi sm, eftekhar b, karbakhsh m. trauma research in iran: a report of the sina trauma data bank. archives of iranian medicine. 2010;13(1):17-20. 2. mayberry jc. imaging in thoracic trauma: the trauma surgeon's perspective. journal of thoracic imaging. 2000;15(2):76-86. 3. brink m, kool d, dekker h, et al. predictors of abnormal chest ct after blunt trauma: a critical appraisal of the literature. clinical radiology. 2009;64(3):272-83. 4. kaewlai r, avery ll, asrani av, novelline ra. multidetector ct of blunt thoracic trauma 1. radiographics. 2008;28(6):1555-70. 5. scaglione m, pinto a, pedrosa i, sparano a, romano l. multidetector row computed tomography and blunt chest trauma. european journal of radiology. 2008;65(3):377-88. 6. livingston dh, shogan b, john p, lavery rf. ct diagnosis of rib fractures and the prediction of acute respiratory failure. journal of trauma and acute care surgery. 2008;64(4):905-11. 7. el wakeel ma, abdullah sm, el khalek rsa. role of computed tomography in detection of complications of blunt chest trauma. menoufia medical journal. 2015;28(2):483. 8. guerrero-lópez f, vázquez-mata g, alcázar-romero pp, fernández-mondéjar e, aguayo-hoyos e, linde-valverde cm. evaluation of the utility of computed tomography in the initial assessment of the critical care patient with chest trauma. critical care medicine. 2000;28(5):1370-5. 9. renton j, kincaid s, ehrlich p. should helical ct scanning of the thoracic cavity replace the conventional chest x-ray as a primary assessment tool in pediatric trauma? an efficacy and cost analysis. journal of pediatric surgery. 2003;38(5):793-7. 10. eckstein m, henderson so. thoracic trauma in rosen’s emergency medicine. philadelphia, mosby elsevier. 2010. 11. exadaktylos a, benneker l, jeger v, et al. total-body digital x-ray in trauma: an experience report on the first operational full body scanner in europe and its possible role in atls. injury. 2008;39(5):525-9. 12. traub m, stevenson m, mcevoy s, et al. the use of chest computed tomography versus chest x-ray in patients with major blunt trauma. injury. 2007;38(1):43-7. 13. safari s, baratloo a, negida as, taheri ms, hashemi b, selkisari sh. comparing the interpretation of traumatic chest x-ray by emergency medicine specialists and radiologists. archives of trauma research. 2014;3(4). 14. chardoli m, hasan-ghaliaee t, akbari h, rahimi-movaghar v. accuracy of chest radiography versus chest computed tomography in hemodynamically stable patients with blunt chest trauma. chinese journal of traumatology. 2013;16(6):351-4. 15. forouzanfar mm, safari s, niazazari m, et al. clinical decision rule to prevent unnecessary chest x‐ray in patients with blunt multiple traumas. emergency medicine australasia. 2014;26(6):561-6. 16. rodriguez rm, anglin d, langdorf mi, et al. nexus chest: validation of a decision instrument for selective chest imaging in blunt trauma. jama surgery. 2013;148(10):940-6. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 89 emergency (2015); 3 (3): 89-94 original research the value of serum nr2 antibody in prediction of post-cardiopulmonary resuscitation survival ali bidari1, samira vaziri2, ehsan moazen zadeh3*, sahar farahmand4, elham talachian5 1. department of emergency medicine, hazrat-e-rasoul akram medical centre, iran university of medical sciences, tehran, iran. 2. department of emergency medicine, firouzgar hospital, iran university of medical sciences, tehran, iran. 3. mental health research centre, tehran psychiatric institute, iran university of medical sciences, tehran, iran. 4. department of emergency medicine, hazrat-e-rasoul akram medical centre, iran university of medical sciences, tehran, iran. 5. department of pediatric gastroenterology, ali asghar children’s hospital, iran university of medical sciences, tehran, iran. *corresponding author: ehsan moazen zadeh; mental health research centre, tehran psychiatric institute, no: 1, mansouri st., niayesh ave., sattarkhan blvd., postal code: 14456-13111, tehran, iran. fax: +98-21-88077892. tel: +98-21-88077892, +98-9128214923; e-mail: moazenzadeh.ehsan@gmail.com received: may 2015; accepted: june 2015 abstract introduction: n-methyl-d-aspartate receptor subunits antibody (nr2-ab) is a sensitive marker of ischemic brain damage in clinical circumstances, such as cerebrovascular accidents. we aimed to assess the value of serum nr2 ab in predicting the post-cardiopulmonary resuscitation (cpr) survival. methods: in this cohort study, we examined serum nr2-ab levels 1 hour after the return of spontaneous circulation (rosc) in 49 successfully resuscitated patients. patients with traumatic or asphyxic arrests, prior neurological insults, or major medical illnesses we re excluded. participants were followed until death or hospital discharge. demographic data, coronary artery disease risk factors, time before initiation of cpr, and cpr duration were documented. in addition, glasgow coma scale (gcs), blood pressure, and survival status of patients were recorded at 1, 6, 24, and 72 hour(s) after rosc. descriptive analyses were performed, and the cox proportional hazard model was applied to assess if nr2-ab level is an independent predictive factor of survival. results: 49 successfully resuscitated patients were evaluated; 27 (55%) survived to hospital discharge, 4 (8.1%) were in vegetative state, 10 (20.4%) were physically disabled, and 13 (26.5%) were physically functional. within 72 hours of rosc all of the 12 nr2-ab positive patients died. in contrast, 31 (84%) of the nr2-ab negative patients survived. sensitivity, specificity, positive and negative likelihood ratios of nr2-ab in prediction of survival were 54.5% (95%ci=32.7%-74.9%), 100% (95%ci=84.5%-100%), infinite, and 45.5% (95%ci=28.8%-71.8%), respectively. subsequent analysis showed that both nr2-ab status and gcs were independent risk factors of death. conclusions: a positive nr2-ab serum test 1 hour after rosc correlated with lower 72-hour survival. further studies are required to validate this finding and demonstrate the value of a quantitative nr2-ab assay and its optimal time of measurement. key words: nr2; outcome; cardiopulmonary resuscitation; survival cite this article as: bidari a, vaziri s, moazen zadeh e, farahmand s, talachian e. the value of serum nr2 antibody in prediction of post-cardiopulmonary resuscitation survival. emergency. 2015;3(3):89-94. introduction: eurological recovery is the ultimate goal of successful cardiopulmonary resuscitation (cpr) (1). however, early post-cpr neurological assessment is a clinical challenge (1). transient cerebral ischemia, sedative medications, and hypothermic resuscitation are common factors that interfere with early postcpr neurological assessment (2, 3). furthermore, there are insufficient data to support the reliability of advanced imaging techniques, including computed tomography (ct) and magnetic resonance imaging (mri), for detection of early ischemic changes, even if they can feasibly be performed in unstable post-cpr patients (2, 4). recently, serum biomarkers have received growing attention for their ability to indicate neuronal ischemic damage. the greatest number of studies have been performed on s100 and neuron specific enolase (nse) (57), and both have failed to show a consistent correlation with post-cpr outcome in multiple studies. no biomarkers have been shown to be useful in the few hours after cardiopulmonary arrest (5). furthermore, increase in serum levels of these biomarkers are not specific to brain tissue injuries, making them questionable as ideal biomarkers (6). there is good evidence that the autoantibody toward nmethyl-d-aspartate receptor subunits (nr2) peptide can n this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com bidari et al 90 serve as an early sensitive neurotoxicity biomarker in ischemic stroke patients (8). the nr2 peptide is a subcomponent of the n-methyl-d-aspartate receptor (nmdar) and is ubiquitously distributed in the central nervous system (9-11). it has been shown that nmdar is cleaved after blood-brain barrier rupture by means of different enzymes, including tissue plasminogen activator (t-pa), resulting in nr2b peptide release and prompting of an ultra-rapid antibody response (12, 13). nr2 antibody (nr2-ab) has been recognised as a neuronal ischemic biomarker. it is useful for differentiation of ischemic strokes from intra-cranial haemorrhages within the first few hours after the event. it also identifies a subgroup of patients with acute transient ischemic attacks (tia) who are at a higher risk for clinical complications (13, 14). when measured in patients who underwent cardiopulmonary bypass for cardiac surgeries, serum nr2-ab was predictive of neurological complications (15). additionally, data from animal models have shown increased levels of nr1, nr2a and, especially nr2b fragments in brain tissues after successful cpr has been performed on animals undergoing asphyxic cardiac arrest (16). based on the above-mentioned points, we primarily raised the question of whether serum nr2-ab could predict poor outcome in successfully resuscitated patients. methods: study design and setting this prospective diagnostic test study was conducted in the emergency departments of two teaching hospitals in tehran, iran, with the annual census around 45000 and 35000 patients, respectively. as a commitment to follow the under mentioned strict inclusion and exclusion criteria, nonprobability convenience sampling was used to recruit the cases in shifts covered by selected authors who served as attending physicians during november, 2011 to december, 2012. the protocol of this study was approved by ethical review board of iran university of medical sciences. written consent was received from close family members of all participants. the code of ethics of the world medical association (declaration of helsinki, as revised in seoul 2008) was fully read and followed in the present work. participants those successfully resuscitated to the point of return of spontaneous circulation (rosc) were considered eligible for the study, if they maintained that condition for at least one uninterrupted hour. patients with age < 18 years, traumatic or asphyxic arrest, head trauma within the past month, pregnant, or a history of disabling disorders, end stage diseases, loss of blood specimen, central nervous system diseases, persistent severe hypoxemia (o2 saturation < 88%) for at least 10 minutes, or required additional cpr attempts within the first hour after rosc were excluded. measurements a 5 ml sample of non-heparinised blood was drawn from a peripheral vein access 1 hour after rosc. we followed the scientific literature and manufacturer instructions for the semi-quantitative enzyme-linked immunosorbent assay (elisa) kit for autoantibodies toward the nr2b fragment of the nmda receptor (human glutamate (nmda) receptor subunit epsilon-2 antibody (nr2b-ab) elisa kit, cusabio, china). briefly, blood samples were centrifuged within 10 min of collection at 3000 cycles/min for 10 min, and the serum was moved and stored at -20 c° immediately. thereafter, the samples were assessed using elisa kits up to two months after the blood sampling date (13). an available microplate reader (micro reader 4 plus, hyperion, usa) was used to read the elisa plates. resuscitation efforts were started either by emergency medicine service personnel or immediately after arrival at emergency department by the emergency department staff, who had been trained to follow the 2010 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science as the standard of care for cardiopulmonary arrest. data collection demographic data, medical history regarding hypertension (htn), diabetes, and hyperlipidemia and smoking background were later collected from several sources, including the patients, if possible, close family members and available medical documents. using a structured checklist, trained emergency medicine residents were responsible for gathering data on the time interval between cardiac arrest and cpr initiation, cpr duration, number of cpr attempts after the first hour of the rosc, gcs, blood pressure, duration of hospitalization, survival outcome at 1, 6, 24, and 72 hours after rosc, and neurological and functional outcome of the patients at the time of hospital discharge. statistical analysis pasw 18.0 software (ibm spss statistics, ibm co., new york, united states) was used to perform all of the statistical analyses. chi square and mann-whitney u tests were applied to compare the categorical and continuous data, respectively. screening performance characteristics of nr2b-ab in prediction of 72-hour survival were calculated. all the reported values were two-sided. to account for the multiple testing effect in the comparison analyses of the baseline characteristics between the survived and non-survived groups, a p < 0.01 was considered significant. using the wald test, variables with significant statistical and clinical differences were selected for the cox proportional hazards model, in which p < 0.05 was considered significant. the mann-whitney u test was employed to compare the gcs scores between the nr2 subgroups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 91 emergency (2015); 3 (3): 89-94 results: 49 successfully resuscitated patients were evaluated; 27 (55%) survived to hospital discharge, 4 (8.1%) were in vegetative state, 10 (20.4) were physically disabled, and 13 (26.5%) were physically functional. the baseline characteristics of the patients are shown in table 1. sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of nr2ab in prediction of survival were 54.5% (95% ci=32.774.9), 100% (95% ci = 84.5-100), 100% (95% ci = 69.9100), 73% (95% ci = 55.6-85.6), infinite, and 45.5% (95% ci=28.8-71.8), respectively. survival analyses within 72 hours of rosc all of the 12 nr2-ab positive patients died. in contrast, 31 (84%) of the nr2-ab negative patients survived, and 27 of them survived to hospital discharge after 1 to 47 days hospitalization (table 2). there were significant differences in mean arterial pressure (map) 1 hour after rosc, nr2-ab, and gcs of survivors and non-survivors (table 1). we omitted map in the cox proportional hazards model because the 10 mmhg mean difference was not clinically significant. the subsequent analysis showed that both nr2-ab status and gcs were independent risk factors for death (table 3). additionally, we found a clinically and statistically significant difference between the gcs scores in the nr2 subgroups, at 1, 6 and 24 hours after rosc (table 4). discussion: based on the results of this study, there was a significant correlation between the positive results of serum nr2ab 1 hour after rosc and 72-hour survival of patients with successful cpr. additionally, in the nr2-ab positive patients, gcs was significantly lower 1, 6, and 24 hours after rosc, indicating a correlation between the biomarker and negative outcome even before all the patients with positive tests had died. our results are in agreement with a multitude of studies that focused on the association of this ischemic neuronal biomarker with the extent of neuronal damage and clinical outcome, particularly for ischemic stroke and tia patients (8, 13, 17). we propose that the underlying pathophysiology of brain ischemia in cardiopulmonary arrest, which is global cerebral hypo perfusion, is similar to the local hypo perfusion observed in tia and cva patients. thus, the mechanism of rise in the serum nr2 antibody level in post-cpr patients could be the same as that in tia and cva patients (16). in addition to the prognostic impact of nr2-ab, we observed that lower map and gcs 1 hour after rosc also were indicative of poor survival outcome. the 10-mmhg difference between mean map values of the two groups was not considered clinically significant. therefore, we disregarded the map values when generating the cox proportional hazard model. we found that each was an independent prognostic factor for survival. our data are in line with the idea of a more extensive approach toward factor inclusion in prognostic models. in our case, this meant the incorporation of both gcs score and serum biomarkers to create a more potent prognostic tool (18). nevertheless, the widespread practice of sedating patients after resuscitation and the increasing application of therapeutic hypothermia in recent years affects the prognostic value of the gcs score (19), further highlighting the importance of alternative prognostic tools such as nr2-ab. an interesting finding of our study was the high specificity of serum nr2-ab level 1 hour after rosc in prediction of survival. to the best of our knowledge, all other time-specific biomarker studies for post-cpr prognostication have used table 1: baseline characteristics of participants characters non-survivors n (%) survivors n (%) p-value* number 22 (44.9) 27 (55.1) male gender 10 (45.5) 14 (51.9) 0.66 age (range) 56.5 (19-75) 53.0 (22-73) 0.94 diabetes 7 (31.8) 5 (18.5) 0.28 hypertension 9 (40.9) 11 (40.7) 0.99 hyperlipidemia 10 (45.5) 5 (18.5) 0.04 smoking 9 (40.9) 7 (25.9) 0.27 arrest to cpr (minute) 10 (0-20) 10 (0-80) 0.35 cpr duration (minute) 32.5 (2-75) 20 (5-70) 0.18 repeated cpr after 1 hour rosc 10 (45.5) 4 (14.8) 0.02 arrest to blood sampling (minute) 100 (62-150) 90 (65-210) 0.19 nr2-ab positive 1 hour after rosc** 12 (54.5) 0 (0) <0.001 gcs# score at 1 hour after rosc 3 (3-5) 7 (3-15) <0.001 map## at 1 hour after rosc (mmhg) 69.2 (65-83) 80 (67-117) <0.001 *mann-whitney u test and chi square test were applied where appropriate, **rosc: return of spontaneous circulation, # gcs: glasgow coma scale, ##map: mean arterial pressure. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com bidari et al 92 a longer time interval for blood sampling. the few studies on nr2-ab, which were conducted in other areas (e.g., tia and cva), chose longer intervals for blood sampling (a minimum of 3 hour after the event) (13). we postulate that the nr2 antibody level will increase in the few hours following an event. that means gaining more survival prediction sensitivity if sampling is repeated later. it remains to be determined whether later measurement of nr2-ab will have sufficient sensitivity to predict neurological outcome in survivors of cardiopulmonary arrest. the ultra-rapid antibody response to nr2 antigen remains a matter of debate. because of the widespread expression of the nmda receptor in the brain and the cerebral endothelial barrier, it is probable that antigenic sensitisation to the nmda receptor occurs through minor neurological incidences, such as trivial head trauma over a person’s lifetime. in this way, an anamnestic response to subsequent antigenic exposures, which occurs immediately after brain injury, can explain the rapidness of the antibody response. this hypothesis is in accordance with the observation that, in acute stroke patients, the serum nr2-ab level distinguishes between patients with or without prior brain ischemic events (17). ubiquitous and exclusive expression of the nmda receptor throughout the cns results in spatial accuracy. moreover, the rapid appearance of both nmda receptor fragments and antibodies denotes temporal sensitivity for the nr2 peptide and antibody. spatio-temporal properties of the nr2-ab may define it as an ideal biomarker in cases of ischemic neuronal injury (6, 20). our finding, that a positive serum nr2-ab within 1 hour after rosc was an independent prognostic factor of survival, supports this theoretical consideration. there are potential wider clinical applications for this test in the future. carbon monoxide poisoning, shock, near-drowning and hypothermia are good examples. those conditions have one thing in common: the extent of hypoxic neurologic damage is the main determinant of prognosis. limitations: there were several limitations to our study. first, nonprobability convenience sampling and a relatively low number of patients were recruited, mainly because of highly selective inclusion criteria. second, relying on a semi-quantitative kit to detect abnormal nr2-ab levels. third, we did not measure the serum nr2-ab level serially. indeed, 45% (n=10) of those who eventually died in their time at the hospital were nr2-ab negative. this suggests that those patients may have had positive test results if it had been repeated later. this is similar to the higher “cumulative sensitivity” that results from the setable 2: cumulative survival rates for resuscitated patients based on serum nr2-ab (antibody) status 1 hour after successful resuscitation antibody outcome time, n (%) total 6 hours 24 hours 72 hours 7 days 14 days 30 days negative died 2 (20) 6 (60) 6 (60) 9 (90) 10 (100) --10 (27) survived 0 (0) 1 (4) 3 (11) 5 (19) 16 (60) 26 (96) 27 (73) positive died 1 (8) 8 (67) 12 (100) ------12 (100) survived ------------0 (0) table 3: cox regression model of nr2 antibody status and glasgow coma scale (gcs) 1 hour after return of spontaneous circulation hazard ratio (95% ci) p-value* nr2 antibody unadjusted 8.33 (3.02-23.01) <0.001 nr2 antibody adjusted for gcs score 3.41 (1.25-9.25) 0.02 gcs score unadjusted 0.306 (0.11-0.84) 0.02 gcs score adjusted for nr2 antibody 0.35 (0.13-0.94) 0.04 *wald test is applied. table 4: comparison of glasgow coma scale (gcs) in different times after successful resuscitation based on serum nr2 antibody status gcs nr2-ab positive* nr2-ab negative* mann-whitney u p-value 1 hour after rosc** 3 (3-3; 3-5) 5 (3-12; 3-15) 100.50 0.002 6 hour after rosc 3 (3-3; 3-5) 8 (5-13; 3-15) 50.50 <0.001 24 hour after rosc 3.00 11 (8-15; 3-15) 1.50 0.006 72 hour after rosc --11.5 (9-15; 3-15) ---- *, median (inter quartile range; range), **rosc: return of spontaneous circulation. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 93 emergency (2015); 3 (3): 89-94 rial measurement of troponin in cases of myocardial infarction (21). fourth, because of funding limitations, we did not assess the nr2 peptide level simultaneously. it is unclear how this co-measurement could have improved the test characteristics. fifth, we applied gcs as a measurement tool for neurological assessment. although gcs was originally employed to predict outcome of patients with traumatic brain injury, it is of value to describe the level of consciousness in non-trauma patients. specifically, it has been used to evaluate the outcome of successfully resuscitated patients (18). conclusion: the status of serum nr2-ab level, 1 hour after rosc, may be a predictor of short-term survival in successfully resuscitated patients. further studies are required to demonstrate whether serial quantitative measurements of serum nr2-ab or a simultaneous measurement of the serum nr2 peptide provides additional prognostication value. acknowledgments: we affirm that no person other than the main authors has contributed to this manuscript. the iran university of medical sciences supported this study. conflict of interest: we declare that the authors of this article have no competing interests. funding support: none. authors’ contributions: ab designed the study and participated in acquisition of data, interpretation of data, drafting manuscript, and revised manuscript for important intellectual content. sv participated in designing the study, acquisition of data, interpretation of data, and drafting manuscript. em carried out statistical analysis and interpretation of data, drafted the manuscript, and revised manuscript for important intellectual content. sf participated in acquisition of data and drafting manuscript. et participated in interpretation of data, and revising manuscript for important intellectual content. all authors read and approved the final manuscript, and agree to be accountable for all aspects of the work. references: 1. becker lb, aufderheide tp, geocadin rg, et al. primary outcomes for resuscitation science studies a consensus statement from the american heart association. circulation. 2011;124(19):2158-77. 2. wijdicks ef, hijdra a, young g, bassetti c, wiebe s. practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review) report of the quality standards subcommittee of the american academy of neurology. neurology. 2006;67(2):203-10. 3. oddo m, rossetti ao. predicting neurological outcome after cardiac arrest. curr opin crit care. 2011;17(3):254-9. 4. friberg h, rundgren m, westhall e, nielsen n, cronberg t. continuous evaluation of neurological 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arash abbasi1,2, pardis mehdipour rabori3, ramtin farajollahi3, kosar mohammed ali4, nematollah ataei1,2, mahmoud yousefifard5∗, mostafa hosseini1,6 † 1. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 2. department of pediatrics, division of nephrology, children’s medical center, tehran university of medical sciences, tehran, iran. 3. student research committee, iran university of medical sciences, tehran, iran. 4. college of medicine, university of sulaimani, sulaimani, iraq. 5. physiology research center, iran university of medical sciences, tehran, iran. 6. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: february 2020; accepted: february 2020; published online: 26 march 2020 abstract: introduction: there is still controversy over the value of renal angina index (rai) in predicting acute renal failure (aki) in children. therefore, the present study aims to provide evidence by conducting a systematic review and meta-analysis on the value of rai in this regard. methods: an extensive search of medline, embase, scopus and web of science databases was conducted by the end of january 2020 using words related to rai and aki. two independent reviewers screened and summarized the related studies. data were analysed using stata 14.0 statistical program and discriminatory precision of rai was assessed. results: data from 11 studies were included. these studies included data from 3701 children (60.41% boys). there were 752 children with aki and 2949 non-aki children. pooled analysis showed that the area under the roc curve of rai in prediction of aki was 0.88 [95% confidence interval (ci): 0.85 to 0.91]. sensitivity and specificity of this tool in predicting aki were 0.85% (95% ci: 0.74% to 0.92%) and 0.79% (95% ci: 0.69% to 0.89%), respectively. the diagnostic odds ratio of rai was 20.40 (95% ci: 9.62 to 43.25). conclusion: the findings of the present meta-analysis showed that rai is a reliable tool in predicting aki in children. keywords: acute kidney injuries; renal insufficiency; severity of illness index; child cite this article as: abbasi a, mehdipour rabori p, farajollahi r, mohamed ali k, ataei n, yousefifard m, hosseini m. discriminatory precision of renal angina index in predicting acute kidney injury in children; a systematic review and meta-analysis. arch acad emerg mede. 2020; 8(1): e39. 1. introduction acute kidney injury (aki) is a serious problem in children and adolescents and can rapidly progress to chronic kidney disease and result in the need for dialysis if not diagnosed in a timely manner. the prevalence of acute renal failure indi∗corresponding author: mahmoud yousefifard, assistant professor of physiology, physiology research center, hemmat highway, tehran, iran. e-mail: yousefifard.m@iums.ac.ir † corresponding author: department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com cates that approximately 10% of children admitted to intensive care units develop aki (1). the effect of this failure on mortality is significant (1, 2). unfortunately, the onset and progression of aki is often asymptomatic and its diagnosis is mainly based on functional biomarkers such as serum creatinine. but in recent years, due to the limitations of creatinine, researchers are seeking an alternative method (1, 3, 8). currently, several diagnostic methods for identifying children with kidney disease are available, but none of them provide a correct picture in the early stages of the disease. meanwhile, the use of scoring systems such as the renal angina index (rai) has received much attention in recent years. rai was first introduced by basu et al. in 2014 to improve the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 2 prediction of aki in critically ill children (9). this study has two phases of derivation and validation. the findings of this study suggest that rai is an acceptable and simple criterion for identifying children at risk for aki. recent research suggests that rai can diagnose aki and predict the patient’s outcome. but there is still disagreement between studies and there is no consensus (10, 11). therefore, the present study aims to provide evidence by conducting a systematic review and meta-analysis on the value of rai in predicting aki in children. 2. methods 2.1. study design the present study is a systematic review and meta-analysis on the diagnostic value of rai in predicting aki in children. the study was designed based on meta-analysis of observational studies in epidemiology (moose) statement (12). 2.2. search strategy in the first step, the keywords associated with aki and rai were identified. then by combining the related keywords using standard tags and boolean operators for each database, a systematic search was performed on medline, embase, scopus, and web of science electronic databases until the end of january 2020. the search query used in medline database is reported in appendix 1. to find additional articles or unpublished data, a manual-search was performed in the bibliography of the relevant studies, google and google scholar. applying this strategy resulted in the addition of two articles to the present study. 2.3. selection criteria in the present study, diagnostic accuracy studies performed on renal angina index in diagnosis of acute renal failure in children were included. inclusion criteria were confirmation of aki via one of the standard methods, sensitivity and specificity (from the article or by contacting the authors) being provided or true positive (tp), true negative (tn)), false positive (fp) and false negative (fn) being provided. both retrospective and prospective studies were included. exclusion criteria were as follows: review studies, studies on adults, duplicate studies (use of same dataset in two studies), and lack of non-aki group. 2.4. data collection and quality assessment after combining the search records and eliminating duplicates, two independent reviewers screened the abstracts and selected potentially relevant studies. then, they assessed and summarized the full-text of eligible studies. in case of disagreement, a third reviewer evaluated the findings and existing disagreement was resolved through discussion. extracted data included first author’s name, year of publication, country, demographic data of patients (age, sex), sample size, standard criterion for defining aki, severity of aki, rai evaluation time, cut-offs used for rai and finally sensitivity, specificity, tp, tn, fp, and fn. the risk of bias was assessed using guidelines proposed in quality assessment of diagnostic accuracy studies 2 (quadas-2) (14). 2.5. statistical analysis statistical analyses were performed using stata version 14.0 (stata corporation, college station, tx). all studies were summarized and categorized based on sensitivity and specificity or tp, tn, fp, and fn. then, the discriminatory power of rai in predicting children’s aki was calculated using the "midas" command, which is a bivariate mixed-effects binary regression modelling framework. results were reported as area under the summary receiver operating characteristics (sroc) curve (auc) with 95% confidence interval (ci). in addition, sensitivity, specificity, negative and positive likelihood ratios and diagnostic odds ratio were calculated. heterogeneity between studies was assessed using i2 test and p value less than 0.1 was considered significant (indicating heterogeneity). publication bias across studies was also assessed using deek’s funnel plot asymmetry test. 3. results 3.1. study characteristics the literature search yielded 2223 records, 2097 of which were non-duplicates. after the initial screening, full texts of 28 articles were studied in detail and finally, the data of 11 articles were included in the present study (15–25) (figure 1). all studies were cohorts. one article contained data from four separate cohorts (15). therefore, the data of each cohort were reported separately. three retrospective cohorts and 11 prospective cohorts were included in the present study. the studied patients were icu admitted in 12 cohorts. these studies included data from 3701 children (60.41% boys). there were 752 children with aki and 2949 non-aki children. the severity of aki was severe in 12 cohorts. all studies had assessed rai status at the time of admission and used a cut-off point of 8 to predict aki. patients were followed up for 3 days in 13 cohorts and until discharge in one cohort. table 1 shows the characteristics of the included studies. 3.2. risk of bias and publication bias across studies risk of bias assessment based on the quadas-2 guidelines showed that the risk of bias in patient selections and flow and timing was unclear in three cohorts. the risk of bias in referthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e39 ence index was unclear in one cohort. also, applicability of patient selection and reference standard was unclear in one cohort. finally, analysis showed that there is no evidence for publication bias in the present study (p = 0.074) (figure 2). 3.3. discriminatory power of rai in aki pooled analysis showed that the auc of rai in paediatric aki prediction was 0.88 (95% ci: 0.85 to 0.91) (figure 3). sensitivity and specificity of this tool in predicting aki were 0.85% (95% ci: 0.74% to 0.92%) and 0.79% (95% ci: 0.69% to 0.89%), respectively (figure 4). positive and negative likelihood ratio of rai in predicting aki in children were 3.96 (95% ci: 2.69 to 5.83) and 0.19 (95% ci: 0.11 to 0.34), respectively (figure 5). finally, the diagnostic odds ratio of rai was 20.40 (95% ci: 9.62 to 43.25) (figure 6). 4. discussion early detection of aki in children can prevent persistent kidney damage such as chronic kidney failure and end-stage renal disease. for this purpose, the present meta-analysis examined the discriminatory power of rai in predicting aki in children on admission. the findings showed that rai is a reliable tool in predicting aki in children. diagnostic odds ratio of rai in predicting aki was about 20, indicating its high applicability in management of the patients. however, there were 7.94% false negatives for rai. although rai has high discriminatory precision, we should consider a proper solutions to reduce its false negative rate. one of these solutions is to add other biomarkers to the rai model. in this regard, a study has shown that adding syndecan-1 to rai increases its predictive value (26). in another study, basu et al. showed that the addition of any of plasma neutrophil gelatinase-associated lipocalin (ngal), matrix metalloproteinase-8 (mmp-8), and neutrophil elastase-2 (ela-2) biomarkers increased the discriminatory power of rai (27). however, further studies are still needed to investigate the cost-effectiveness of adding a new biomarker to rai. the lowest sensitivity for rai was reported in the study by the basu et al. this multicenter study had the largest sample size among the included studies. the sensitivity and specificity of rai in this study were 33% and 86%, respectively (16). the findings of this study may be outliers. we performed an additional analysis after excluding the basu et al. article. the findings showed that omitting this article did not have a significant effect on the reported sensitivity (0.87 vs. 0.85) and specificity (0.78 vs. 0.79) of rai in detection of aki. in the present meta-analysis, 14 cohort studies (from 11 articles) were included, 3 of which were retrospective and 11 were prospective. the retrospective nature of these studies partly influenced the quality of the published articles and led to an unclear risk of bias in patient selection. in addition, one study (21) did not indicate the reference index used for classification of children to aki and non-aki. therefore, the status of this study in the reference index section was unclear. however, the risk of bias and applicability of most studies were low, which is a strong point for the present study. 5. conclusion the present meta-analysis summarized evidence on the discriminatory power of rai at the time of admission in predicting aki in children and adolescents. the findings of this study showed that rai is a reliable tool in predicting aki in children. 6. declarations 6.1. acknowledgements we are grateful to dr. mastaneh moghtaderi and dr. mojtaba fazel for their valuable helps. 6.2. authors contributions study design: mahmoud yousefifard, mostafa hosseini data gathering: arash abbasi, pardis mehdipour rabori, ramtin farajollahi analysis and interpreting the result: mahmoud yousefifard, mostafa hosseini, kosar mohammad ali drafting the manuscript: mahmoud yousefifard, kosar mohammad ali critically revised the paper: all authors all authors approved the final version of manuscript and are accountable for all aspects of the work. authors orcids arash abbasi: 0000-0002-8859pardis mehdipour rabori: 0000-0001-5268-2267 ramtin farajollahi: 0000-0001-6728-3613 kosar mohammad ali: 0000-0001-5533-2924 nematollah ataei: 0000-0001-9682-4394 mahmoud yousefifard: 0000-0001-5181-4985 mostafa hosseini: 0000-0002-1334-246x 6.3. funding support this study was funded and supported by tehran university of medical sciences (tums); grant no. 98-01-184-42136. 6.4. conflict of interest there is no conflict of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 4 references 1. schneider j, khemani r, grushkin c, bart r. serum creatinine as stratified in the rifle score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. critical care medicine. 2010;38(3):933-9. 2. goldstein sl, devarajan p. pediatrics: acute kidney injury leads to pediatric patient mortality. nature reviews nephrology. 2010;6(7):393-4. 3. murray pt, devarajan p, levey as, eckardt ku, bonventre jv, lombardi r, et al. a framework and key research questions in aki diagnosis and staging in different environments. clinical journal of the american society of nephrology : cjasn. 2008;3(3):864-8. 4. devarajan p. update on mechanisms of ischemic acute kidney injury. journal of the american society of nephrology : jasn. 2006;17(6):1503-20. 5. nickolas tl, barasch j, devarajan p. biomarkers in acute and chronic kidney disease. current opinion in nephrology and hypertension. 2008;17(2):127-32. 6. devarajan p. review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. nephrology (carlton, vic). 2010;15(4):41928. 7. coca sg, yalavarthy r, concato j, parikh cr. biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. kidney international. 2008;73(9):1008-16. 8. coca sg, parikh cr. urinary biomarkers for acute kidney injury: perspectives on translation. clinical journal of the american society of nephrology : cjasn. 2008;3(2):48190. 9. basu rk, zappitelli m, brunner l, wang y, wong hr, chawla ls, et al. derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. kidney international. 2014;85(3):659-67. 10. basu rk, wang y, wong hr, chawla ls, wheeler ds, goldstein sl. incorporation of biomarkers with the renal angina index for prediction of severe aki in critically ill children. clinical journal of the american society of nephrology. 2014;9(4):654-62. 11. menon s, goldstein sl, mottes t, fei l, kaddourah a, terrell t, et al. urinary biomarker incorporation into the renal angina index early in intensive care unit admission optimizes acute kidney injury prediction in critically ill children: a prospective cohort study. nephrology dialysis transplantation. 2016;31(4):586-94. 12. stroup df, berlin ja, morton sc, olkin i, williamson gd, rennie d, et al. meta-analysis of observational studies in epidemiology. jama: the journal of the american medical association. 2000;283(15):2008-12. 13. moher d, liberati a, tetzlaff j, altman dg. preferred reporting items for systematic reviews and meta-analyses: the prisma statement. annals of internal medicine. 2009;151(4):264-9. 14. whiting pf, rutjes aw, westwood me, mallett s, deeks jj, reitsma jb, et al. quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies. annals of internal medicine. 2011;155(8):529-36. 15. basu rk, zappitelli m, brunner l, wang y, wong hr, chawla ls, et al. derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. kidney international. 2014;85(3):659-67. 16. basu rk, kaddourah a, goldstein sl, akcan-arikan a, arnold m, cruz c, et al. assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study. the lancet child and adolescent health. 2018;2(2):112-20. 17. gawadia j, mishra k, kumar m, saikia d. prediction of severe acute kidney injury using renal angina index in a pediatric intensive care unit. indian pediatrics. 2019;56(8):647-52. 18. hanson hr, carlisle ma, bensman rs, byczkowski t, depinet h, terrell tc, et al. early prediction of pediatric acute kidney injury from the emergency department: a pilot study. american journal of emergency medicine. 2020:[in press]. 19. kaur r, dhooria gs, pooni pa, bhat d, bhargava s, kakkar s, et al. utilization of the renal angina index in picu of a developing country for prediction of subsequent severe acute kidney injury. pediatric nephrology (berlin, germany). 2018;33(11):2185-91. 20. menon s, goldstein sl, mottes t, fei l, kaddourah a, terrell t, et al. urinary biomarker incorporation into the renal angina index early in intensive care unit admission optimizes acute kidney injury prediction in critically ill children: a prospective cohort study. nephrology, dialysis, transplantation : official publication of the european dialysis and transplant association european renal association. 2016;31(4):586-94. 21. ma. p, f. a. diagnostic accuracy of renal angina index in predicting acute kidney injury in pediatric patients with sepsis: a philippine tertiary hospital experience. pediatric infectious disease society of the philippines journal. 2018;19(1):32-9. 22. sethi sk, raghunathan v, shah s, dhaliwal m, jha p, kumar m, et al. fluid overload and renal angina index at admission are associated with worse outcomes in critically ill children. frontiers in pediatrics. 2018;6:7. 23. sundararaju s, sinha a, hari p, lodha r, bagga a. renal this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e39 angina index in the prediction of acute kidney injury in critically ill children. asian journal of pediatric nephrology. 2019;2(1):25-31. 24. youssef d, mansour s, el_shal a, osman a, yousif y, arab f, et al. renal angina validation of acute kidney injury in critically ill children. geget. 2019;14(2):47-53. 25. zeid ama, mohammed dy. urinary ngal incorporation into renal angina index for early detection of acute kidney injury in critically ill children. j clini nephrol. 2019;3:93-9. 26. de melo bezerra cavalcante ct, castelo branco km, pinto junior vc, meneses gc, de oliveira neves fm, de souza nm, et al. syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery. the journal of thoracic and cardiovascular surgery. 2016;152(1):178-86.e2. 27. basu rk, wang y, wong hr, chawla ls, wheeler ds, goldstein sl. incorporation of biomarkers with the renal angina index for prediction of severe aki in critically ill children. clinical journal of the american society of nephrology : cjasn. 2014;9(4):654-62. 7. appendix 1: search query in medline via pubmed (renal angina index[all field] or renal angina[all field]) and ("acute kidney injury"[mh] or "renal insufficiency"[mh] or "kidney tubular necrosis, acute"[mh] or acute kidney injuries [tiab] or kidney injuries, acute[tiab] or kidney injury, acute[tiab] or acute renal injury[tiab] or acute renal injuries[tiab] or renal injuries, acute[tiab] or renal injury, acute[tiab] or renal insufficiency, acute[tiab] or acute renal insufficiencies[tiab] or renal insufficiencies, acute[tiab] or acute renal insufficiency[tiab] or kidney insufficiency, acute[tiab] or acute kidney insufficiencies[tiab] or kidney insufficiencies, acute[tiab] or acute kidney insufficiency[tiab] or kidney failure, acute[tiab] or acute kidney failures[tiab] or kidney failures, acute[tiab] or acute renal failure[tiab] or acute renal failures[tiab] or renal failures, acute[tiab] or renal failure, acute[tiab] or acute kidney failure[tiab] or kidney cortex necrosis[tiab] or renal insufficiencies[tiab] or kidney insufficiency[tiab] or insufficiency, kidney[tiab] or kidney insufficiencies[tiab] or kidney failure[tiab] or failure, kidney[tiab] or failures, kidney[tiab] or kidney failures[tiab] or renal failure[tiab] or failure, renal[tiab] or failures, renal[tiab] or renal failures[tiab] or lower nephron nephrosis[tiab] or lower nephron nephroses[tiab] or nephron nephroses, lower[tiab] or nephron nephrosis, lower[tiab] or nephroses, lower nephron[tiab] or nephrosis, lower nephron[tiab] or acute kidney tubular necrosis[tiab] or kidney cortical necrosis[tiab] or necrosis, kidney cortex[tiab] or renal cortex necrosis[tiab] or renal cortical necrosis[tiab] or kidney tubule necrosis[tiab] or kidney tubular epithelium necrosis[tiab] or kidney tubular necrosis[tiab] or kidney tubular necrosis, acute[tiab] or kidney tubulus necrosis[tiab] or necrosis, kidney tubule[tiab] or necrotic tubulonephrosis[tiab] or renal tubular cell necrosis[tiab] or renal tubular necrosis[tiab] or renal tubule necrosis[tiab] or renal tubulus necrosis[tiab] or tubular necrosis[tiab] or tubule necrosis[tiab] or tubule necrosis, kidney[tiab] or tubulus necrosis[tiab]) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 6 table 1: characteristics of included studies author; year; country study type setting of patients age no. aki; nonaki no. boys aki definition aki severity rai time; cutoffs follow up tp fp tn fn basu, cohort 1; 2014; usa rcs sepsis 0.2 to 12.5 28; 116 83 kdigo severe 0; 8 3 21 31 85 7 basu, cohort 2; 2014; canada rcs icu admitted 0.2 to 12.5 12; 106 74 kdigo severe 0; 8 3 7 11 95 5 basu, cohort 3; 2014; canada pcs icu admitted 0.2 to 12.5 11; 97 64 kdigo severe 0; 8 3 10 27 70 1 basu, cohort 4; 2014; usa pcs icu admitted 0.2 to 12.5 29; 185 134 kdigo severe 0; 8 3 27 118 67 2 basu; 2018; multicenter pcs icu admitted 2 to 14.5 553; 1037 882 kdigo severe 0; 8 3 121 165 1057 247 gawada; 2019; india pcs icu admitted 0.1 to 12 114; 48 95 kdigo severe 0; 8 3 62 24 74 2 hanson; 2020; usa pcs icu admitted 0.1 to 25 17; 64 38 kdigo any aki 0; 8 inhospital 16 10 54 1 kaur; 2018; india pcs icu admitted 0.1 to 18 53; 360 301 kdigo severe 0; 8 3 25 44 336 8 menon; 2016; usa pcs icu admitted 0.2 to 25 15; 141 98 kdigo severe 0; 8 3 12 40 101 3 perez; 2018; philippine rcs sepsis <19 90; 132 130 nr nr 0; 8 3 87 8 124 3 sethi; 2018; india pcs icu admitted 6.5±5.9 months 33; 69 69 kdigo severe 0; 8 3 27 21 48 6 sundararaju; 2019; india pcs icu admitted 0.1 to 18 29/256 189 kdigo severe 0; 8 3 24 117 139 5 youssef; 2019; egypt pcs icu admitted 0.2 to 14 13; 40 34 prifle severe 0; 8 3 10 1 39 3 zeid; 2019; egypt pcs icu admitted 0.2 to 7 10; 43 45 prifle severe 0; 8 3 9 16 27 1 aki: acute kidney injury; fn: false negative; fp: false positive; kdigo: kidney disease improving global outcomes; nr: not reported; pcs: prospective cohort study; prifle: pediatric risk, injury, failure, loss, end stage renal disease; rcs: retrospective cohort study; tn: true negative; tp: true positive; icu: intensive care unit. table 2: risk of bias assessment risk of bias applicability patient selection index test reference standard flow and timing patient selection index test reference standard basu; 2014; cohort 1 a © © a © © © basu; 2014; cohort 2 a © © a © © © basu; 2014; cohort 3 © © © © © © © basu; 2014; cohort 4 © © © © © © © basu; 2018 © © © © © © © gawada; 2019 © © © © © © © hanson; 2020 © © © © © © © kaur; 2018 © © © © © © © menon; 2016 © © © © © © © perez; 2018 a © a a a © a sethi; 2018 © © © © © © © youssef; 2019 © © © © © © © zeid; 2019 © © © © © © © ©: low risk; a: unclear this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e39 figure 1: prisma flow diagram of present meta-analysis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 8 figure 2: risk of bias and publication bias assessments. there is no evidence. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e39 figure 3: area under the summary receiver operative characteristics (sroc) curve (auc). sens: sensitivity; spec: specificity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 10 figure 4: sensitivity and specificity of renal angina index in prediction of acute kidney injury. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e39 figure 5: positive and negative diagnostic likelihood ratios (dlr) of renal angina index in prediction of acute kidney injury. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. abbasi et al. 12 figure 6: diagnostic score and diagnostic odds ratio of renal angina index in prediction of acute kidney injury. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references appendix 1: search query in medline via pubmed emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 54 emergency (2014); 2 (2): 54-58 educational reveiw poisonous spiders: bites, symptoms, and treatment; an educational review farzad rahmani1*, seyed mahdi banan khojasteh2, hanieh ebrahimi bakhtavar3, farnaz rahmani4, kavous shahsavari nia5, gholamreza faridaalaee6 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. department of animal biology, faculty of natural sciences, university of tabriz, tabriz, iran 3. department of emergency medicine, ardabil university of medical sciences, ardabil, iran 4. department of psychiatric nursing, school of nursing and midwifery, tabriz university of medical sciences, tabriz, iran 5. road traffic injury research center, tabriz university of medical sciences, tabriz, iran 6. department of emergency medicine, urmia university of medical sciences, urmia, iran abstract more than 40,000 species of spiders have been identified in the world. spider bites is a common problem among people, however few of them are harmful but delay in treatment can cause death. since the spider bites are risk full to human, they should be taken seriously, especially in endemic areas. our objective in this review was to study about poisonous spiders and find out treatments of them. therefore, we collected related articles from pubmed database and google scholar. three important syndromes caused by spider bites are loxoscelism, latrodectism and funnel web spider syndrome. many treatments are used but much more studies should have done to decrease the mortality. in this review, we describes different venomous spiders according to their appearance, symptoms after their bites and available treatments. key words: spiders; spider bites; spider venoms; black widow spider; emergency treatment cite this article as: rahmani f, banan khojasteh m, ebrahimi bakhtavar h, rahmani f, shahsavari nia k, faridaalaee gh. poisonous spiders: bites, symptoms, and treatment; an educational review. emergency. 2014;2(2):54-8. introduction:1 piders belong to a branch of invertebrate animals called arthropods. arthropods have the largest number of species. along with ticks, mites and scorpions, spiders fall into the subphylum chelicerata and class of arachnids (1, 2). the arachnid class has very diverse members in a way that more than 80,000 species belonging to that class have been identified to date. spiders are a large group of arachnids belonging to the araneae order (1). more than 40,000 species of spider have been identified to date but the real number is estimated at 4 times more than that number (3). except for two small groups in the arachnid family, all spiders have poison glands and release their secretions into their venom sacs near their chelicerae. however, the majority of spiders do not bite humans and except for a few cases, they are not harmful to the human being or other mammals (2).spider bites are common but the majority of species create little clinical presentations (3). there is only one aggressive spider named funnelweb in australia, which attacks the human being without provocation. the majority of venomous spiders are found in latin america. these large spiders are quite *corresponding author: farzad rahmani, md; emergency medicine department, imam reza hospital, tabriz university of medical sciences, golgasht avenue, tabriz, iran. postal code: 5166614756. phon/fax: 00984113352078. email: farzadrhn88@gmail.com received: 7march 2014; accepted: 27 march 2014 aggressive and their venom is pharmacologically highly toxic. their bite results in severe pain, neurotoxic effects, diaphoresis, severe allergic reaction and priapism (1). other spiders normally exhibit aggressive behavior after being trapped, injured or provoked. the severity of reactions to spider venom depends on factors such as its amount, site of biting and its duration and age and health condition. mortality due to spider bite is rare (2). spider venom includes different peptides and substances affecting sodium, calcium and potassium channels in neurons and also glutamate and acetylcholine receptors (4).spider bite victims develop symptoms such as pain and swelling in the site of biting, necrosis, pyrexia, pulmonary edema, respiratory distress, hypertension, kidney dysfunction and death. treatment protocol in the case of critically ill patients includes supportive measures and antivenom injection. respiratory support and monitoring the hemodynamic status of these patients are of fundamental importance (5). highly venomous spiders, funnel-web in australia and armadeiras (armed spiders) in south america require antivenom and intensive therapeutic interventions (6). three important syndromes are caused by spider bites: latrodectism, loxoscelism, and funnel-web spider syndrome (7). here, we discuss about poisonous spiders and find out treatments of them. s this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 55 rahmani et al introduction of venomous spiders this section describes different venomous spiders according to their appearance, symptoms after their bites and available treatments. therefore, we collected related articles from pubmed and google scholar (figure 1). a) the brown recluse spider the brown recluse spider is recognized by the violinshaped marking on its back (figure 2). this spider takes rest during the day and is not aggressive but it will attack in the case of provocation. patients are usually bitten by wearing clothes and shoes with spiders in them (2). loxoscelism syndrome is the symptoms caused by the bite of the brown recluse spider. this spider's bite is usually painless but it later becomes an inflammatory, hemorrhagic and painful lesion (8). necrosis spreads a few days following the bite and loxoscelism syndrome results in dermatitis necrosis in the site of biting, around which becomes red, white and blue, respectively (9). the venom of this spider contains hyaluronidase and sphingomyelinase d enzymes and results in necrosis. moreover, neutrophil activity and platelet aggregation and thrombosis exacerbate necrosis (8). local manifestations of the bite of this spider include edema, inflammation, hemorrhage, damage to the vessel wall, thrombosis, and necrosis (10) but systematic symptoms including acute renal failure, rhabdomyolysis and intravascular hemolysis have also been reported (11). in some cases, severe coagulopathy can result in stroke (7).considering extensive differential diagnosis for skin necrosis, the standard criteria for the diagnosis of loxoscelism syndrome is capturing the spider during biting or capturing it in the place where biting occurred and its confirmation by a reliable arachnologist(12). dapsone, antihistamines, colchicine, corticosteroids and hyperbaric oxygen have been used for treatment. treatment with dapsone can alleviate bite marks and symptoms (8, 13). antivenom reduces the size of the necrotic area. the faster the antivenom is administered, the less the manifestations. it has been proven useful during the first 4 hours after the bite but according to an investigation, it was useful even after 12 hours (14). the bite-induced necrosis spreads in a few days and completes in a few weeks. treatments include initial debridement and in later stages, after improvement of the inflammation, graft is used in case of severity (9). b) hobo spider hobo spider is a brown-colored spider with gray marks along its body (figure 3). the reason for its name is its aggressive behavior following slight provocation. symptoms induced by its bite are similar to those of the brown recluse spider but necrosis is rare and permanent scar is probable on the site of biting (12). the cause of necrosis is the hemolytic property of the venom or transmission of pathogenic bacteria inside the site of biting (15). the systemic symptoms of biting are reportedly cephalalgia and in some, rare cases anaphylaxis and death. the treatment is similar to that of the brown recluse spider. moreover, resection should not be conducted before the completion of the necrosis process (8). c) black widow spider black widow spiders have a black hairless body. males are smaller than females. its major characteristic is a red marking on its abdomen similar to an hourglass (figure 4). it is not aggressive under normal circumstances but attacks if disturbed, especially while protecting its egg sacs. moreover, it is the most important venomous spider in north america and australia (2, 3). its venom is alpha-latrotoxin (neurotoxic venom) which results in the exocytosis of synaptic vesicles from parasympathetic terminals due to the stimulation of calcium-dependent mechanisms, releasing catecholamines and acetylcholine (8). the symptoms induced by the bite of this spider are called latrodectism. the pain from its bite is similar to that of a pinprick. a lesion similar to the target lesion can be observed in the site of biting (16).latrodectism starts in a few minutes with the development of pain studies include in qualitative synthesis n=25 observational 10 review 7 book 2 case report 2 randomized clinical trial 1 case series 1 photo quiz 1 guideline 1 excluded by published in other language (except english or persian) and/or full text review: 21 records excluded by abstract and/or full text review: 211 records duplicate records: 6 records studies that we could not access abstract or full text of them: 9 records total search result: 272 records additional records identified in google scholar: 2 records primary search result: 270 records figure 1: flowchart of study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 54-58 56 through the whole body and symptoms such as emesis, respiratory failure, delirium, partial paralysis of limbs, abdominal muscle cramps, hypertension, pyrexia, fasciculation and muscle spasm are developed within a few hours (17). symptoms may be mistaken with acute abdomen. mortality following biting is less than 1 % and the risk of death following biting is high in two age spectrums. bites usually occur during warm months (7). the chelicerae of this spider rarely leave a mark. following the bite, erythema, diaphoresis and piloerection are observed around the site of bite in 25 % of the cases (3). diagnosis is based on the patient's history. while it can be difficult in children, hypertension, distress, diaphoresis and irritability can suggest diagnosis in these cases (18). the treatment of these patients consists of using muscle relaxants, narcotics, analgesics, intravenous calcium and antivenom. narcotics and benzodiazepines relieve muscle spasms. antivenom treatment is recommended for children, pregnant women the elderly and also patients with severe local symptoms, severe pains necessitating repeated administration of narcotics and systematic symptoms (3). in the case of iv administration, the antivenom should be diluted and injected slowly (17). however, some centers have recommended im administration in order to reduce its complications. in the case of im administration, the effect is delayed and symptoms take longer to improve (3) (within 1-5 days). some may suffer from chronic pains even after proper antivenom treatment (18). d) armadeiras (armed spiders) armed spiders have long arms. since they often hide in banana boxes, they are known as banana bunch spiders by locals (figure 5).the symptom of its bite is severe figure 2: brown recluse spider. photograph by richard s.vetter.reproduced with permission from:australianmuseum.net.au figure 3: eratigena-agrestis (hobo) spider. reproduced with permission from:www.spiders.us figure 4: black widow spider (photograph by eric r. eaton. reproduced with permission from bugeric.blogspot.com figure 5: phoneutria, commonly known as brazilian wandering spider or armed spider. image source:wikipedia.org this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 57 rahmani et al pain which is observed in 96 % of patients (18). the bite of this spider can cause respiratory failure and death at both ends of the age spectrum (8). its venom is neurotoxic thus stimulates the autonomic nervous system (tachycardia, hypertension, diaphoresis and salivation), priapism, dizziness and visual disturbances (19). this venom is recommended to be used for controlling permanent pathological pains due to its different compounds and its effect on pain neurons (20). patients receive supportive treatment including pain and symptom control. there is antivenom for the treatment of these patients but it is used in few cases (21). with regard to the probability of respiratory failure in these patients, it is contradictory to use narcotics for pain control. therefore, local nerve block anesthesia is recommended (8). e) funnel-web spider funnel-web spider, the most dangerous spider in the world, is aggressive in the absence of provocation (figure 6) (3). the structure of this spider’s web is funnel-shaped, hence the name (8).the venom of this spider is neurotoxin and contains a large amount of peptides (22, 23). delta atracotoxin, one of the peptides in the venom, delay the activation of voltage-dependent sodium channels resulting in repeated stimulation and release of massive neurotransmitters in nerve endings (24). robustoxin is another toxin in the venom of this spider which is a fatal peptide and can be used for immunization (25). local symptoms include pain, diaphoresis, hives and piloerection. systemic symptoms include stimulation of the parasympathetic system (nausea, emesis, salivation, sialorrhea and tearing), cardiovascular system (hypertension, mostly tachycardia and in some rare cases bradycardia and hypotension), nervous system (fasciculation and perioral paresthesia), non-cardiac pulmonary edema (more prevalent in children), agitation, and cephalalgia(3). treatment includes supportive measures, elastic bandage for blocking lymph flow, limb immobilization and rapid transportation to the hospital. antivenom is the definite cure and should be administered up to 15 minutes after opening the bandage. in the case of uncertainty about the bite and exhibition of the first systemic symptoms, 2 vials of antivenom are administered and in the case of severe symptoms 4 vials are administered. other therapeutic measures include hemodynamic support, ventilatory support and the administration of tetanus vaccine. these measures reduce the risk of neurological complications and mortality and improve the performance of patients after being discharged (7). f) tarantula tarantula is recognized by its hairy 3-inch brown or black colored body (figure 7). this type of spider is kept as pet (8). its venom is not dangerous for the human being and merely creates lesions without any specific systemic reaction except for pyrexia. tarantula’s defense mechanism is the hair on its body which stands out and moves when alarmed (2). if these hairs enter the eye, they can result in the inflammation of all of the layers of the eye. eye wash and topical corticosteroids are recommended in the case of uveitis (8). recommendations for future the human being has always been frightened of spiders but few of them are venomous and thus real threat to human health. however, since venomous spiders are sometimes fatal, bites should be taken care of. moreover, it is recommended to be adequately familiar with necessary treatments. with regard to the identification of venomous spiders in our country including widow spider, which exists in the majority of provinces, healthcare personnel must be familiar with the symp figure 6: funnel web spider (reproduced with permission from australianmuseum.net.au figure 7: tarantula spider (mexican red legged tarantula) photograph byricbolzan. reproduced with permission fromaustralianmuseum.net.au  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 54-58 58 toms of the bites of venomous spiders and it is essential to prepare antivenoms in the country for the treatment of spider bites. finally, further domestic investigations are necessary on the distribution of venomous spiders and suspected cases of spider bite should be reported to related centers to reduce the damages caused by biting. acknowledgments: we acknowledge managers of www.spiders.us;www. australianmuseum.net.au; www.bugeric.blogspot.com; and ww w.wikipedia.orgsites for let us to use their own images. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. hickman c, roberts l, keen s, larson a, i’anson h, eisenhour d. integrated principles of zoology. 14 ed. china: mcgrawhill; 2008. p. 402-12. 2. diaz jh, leblanc ke. common spider bites. am fam physician. 2007;75(6):869-73. 3. braitberg g, segal l. spider bites: assessment and management. aust fam physician. 2009;38(11):862-7. 4. rajendra w, armugam a, jeyaseelan k. toxins in anti-nociception and anti-inflammation. toxicon. 2004;44(1):1-17. 5. ahmed kz, bushra r. antivenom therapy of spider bite envenomation. pak j pharmacol. 2008;25(2):39-45. 6. vetter rs, isbister gk. medical aspects of spider bites. annu rev entomol. 2008;53:409-29. 7. garcia h, tanowitz h, del brutto o. neurological effects of venomous bites and stings: snakes, spiders, and scorpions. neuroparasitology and tropical neurology: handbook of clinical neurology series (editors: aminoff, boller, swaab). 2013;114:349-68. 8. tintinalli je, stapczynski js, ma oj, cline d, cydulka r, meckler g. tintinalli's emergency medicine: a comprehensive study guide: mcgraw-hill medical; 2011. p. 1344-54. 9. garza ocañas l, mifuji rm. cutaneous loxoscelism. n engl j med. 2013;369(5):495-500. 10. isbister gk, fan hw. spider bite. the lancet. 2011;378(9808):2039-47. 11. malaque c, santoro ml, cardoso jlc, et al. clinical picture and laboratorial evaluation in human loxoscelism. toxicon. 2011;58(8):664-71. 12. bennett rg, vetter rs. an approach to spider bites. erroneous attribution of dermonecrotic lesions to brown recluse or hobo spider bites in canada. can fam physician. 2004;50(8):1098-101. 13. bogdán s, barabás j, zacher g, et al. total upper lip necrosis and loxoscelism caused by violin spider bite. orv hetil. 2005;146(45):2317-21. 14. pauli i, minozzo jc, henrique da silva p, chaim om, veiga ss. analysis of therapeutic benefits of antivenin at different time intervals after experimental envenomation in rabbits by venom of the brown spider (loxosceles intermedia). toxicon. 2009;53(6):660-71. 15. gaver-wainwright mm, zack rs, foradori mj, lavine lc. misdiagnosis of spider bites: bacterial associates, mechanical pathogen transfer, and hemolytic potential of venom from the hobo spider, tegenaria agrestis (araneae: agelenidae). j med entomol. 2011;48(2):382-8. 16. shlamovitz gz. man with back pain. ann emerg med. 2011;58(5):496-500. 17. nordt sp, clark rf, lee a, berk k, lee cantrell f. examination of adverse events following black widow antivenom use in california. clin toxicol. 2012;50(1):70-3. 18. monte aa, bucher-bartelson b, heard kj. a us perspective of symptomatic latrodectus spp. envenomation and treatment: a national poison data system review. ann pharmacother. 2011;45(12):1491-8. 19. gewehr c, oliveira sm, rossato mf, et al. mechanisms involved in the nociception triggered by the venom of the armed spider phoneutria nigriventer. plos negl trop dis. 2013;7(4):e2198. 20. souza ah, ferreira j, cordeiro mdo n, et al. analgesic effect in rodents of native and recombinant ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. pain. 2008;140(1):115-26. 21. isbister gk, graudins a, white j, warrell d. antivenom treatment in arachnidism: antivenoms. clin toxicol. 2003;41(3):291-300. 22. liu j, gao j, yun y, hu z, peng y. bioaccumulation of mercury and its effects on survival, development and webweaving in the funnel-web spider agelena labyrinthica (araneae: agelenidae). bull environ contam toxicol. 2013;90(5):558-62. 23. palagi a, koh j, leblanc m, et al. unravelling the complex venom landscapes of lethal australian funnel-web spiders (hexathelidae: atracinae) using lc-maldi-tof mass spectrometry. j proteomics. 2013;80:292-310. 24. pineda ss, wilson d, mattick js, king gf. the lethal toxin from australian funnel-web spiders is encoded by an intronless gene. plos one. 2012;7(8):e43699. 25. comis a, tyler m, mylecharane e, spence i, howden m. immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (atrax robustus) venom. j biosci. 2009;34(1):35-44. archives of academic emergency medicine. 2019; 7 (1): e32 or i g i n a l re s e a rc h management of preventable deaths due to road traffic injuries in prehospital phase; a qualitative study adel eftekhari1, abbasali dehghanitafti1, khadijeh nasiriani2, majid hajimaghsoudi3, hossein fallahzadeh4, davoud khorasani-zavareh5∗ 1. department of health in emergencies and disasters, school of public health, shahid sadoughi university of medical sciences, yazd, iran. 2. department of nursing, school of nursing and midwifery, shahid sadoughi university of medical sciences, yazd, iran. 3. trauma research center, shahid rahnemoon hospital, shahid sadoughi university of medical sciences, yazd, iran. 4. department of biostatistics and epidemiology, school of public health, shahid sadoughi university of medical sciences, yazd, iran. 5. department of health in emergencies and disasters, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. received: april 2019; accepted: may 2019; published online: 24 june 2019 abstract: introduction: prehospital care plays an important role in decreasing the number of deaths due to road traffic injuries (rtis). this study aimed to identify the challenges of preventable deaths due to rtis in the prehospital phase based on the attitudes of stakeholders. methods: conventional content analysis of qualitative study was used to analyze the data. the participants were 24 rti prevention experts from fire-fighting organization, traffic police, the red crescent, emergency medical services staff, emergency medicine specialists, and hospital emergency nurses who were selected by means of purposive sampling. data were collected using unstructured interviews and analyzed by means of data coding, followed by extracting sub-categories, and main categories. results: six main categories were extracted as the major challenges of preventable deaths in rtis in the prehospital phase including “poor management of the crash scene” with two subcategories of lack of rapid access to the patient and lack of scene safety, “lack of adequate rules and regulations” with two subcategories of lack of protocols and guidelines and lack of clear duties checklists, “poor management of time” with two subcategories of elongated response time at the crash scene and elongated time of victim transport, “low quality of training” with two subcategories of insufficient training of emergency medical services (ems) staff and inadequate public training, “poor communication and coordination” with two subcategories of poor communication of ems staff and lack of uniform commandership at the crash scene, and “low quality of victim management” with two subcategories of low quality of clinical care and lack of accurate clinical assessment. conclusion: the following measures are necessary to reduce preventable deaths due to rtis in the prehospital phase: accurate clinical assessment of the victim on the scene, provision of high quality and accurate clinical care, enforcement of legal obligations and using protocols in the field of victim management, coordination of the involved organizations through identifying the duties and responsibilities of each organization, and full management of the crash scene by assigning a unique commander to each unit and creation of the highest level of safety on crash scene. keywords: death; emergency medical services; accidents, traffic cite this article as: eftekhari a, dehghanitafti a, nasiriani kh, hajimaghsoudi m, fallahzadeh h, khorasani-zavareh d. management of preventable deaths due to road traffic injuries in prehospital phase; a qualitative study. arch acad emerg med. 2019; 7(1): e32. ∗corresponding author: davoud khorasani-zavareh, department of health in emergencies and disasters, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. tel: +98 2122439982, fax: +98 2122439784, e-mail: davoud.khorasani@gmail.com 1. introduction according to the world health organization (who), road traffic injuries (rtis) account for about 1.3 million deaths worldwide annually and are the major cause of death among individuals aged 15-29 years (1, 2). the rate of mortality due to rtis is constantly increasing in many countries, especially in lowand middle-income countries (lmics) and 93% of all this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. eftekhari et al. 2 rti victims live in such countries (3). although fatal rtis may occur at the crash scene, during patient transport, or in the hospital (4), according to some reports, most deaths occur in the prehospital phase in lowand middle-income countries lmics (5). previous studies have indicated that 86% of trauma-related deaths occur in the prehospital phase (6); and about 39% of them are preventable (4). the presence of a systematic approach towards rtis (7), and providing prehospital care aiming at higher quality emergency care to reduce victims’ mortality, play a pivotal role in effective management of these deaths (3). moreover, selection of appropriate strategies and correct policy-making in these conditions may lead to decreased rates of death due to rtis in different countries (8, 9). according to who, in most countries lack of sufficient information on preventable deaths in the prehospital phase is one of the major obstacles in suitable planning for reducing these deaths. preventable deaths, as a concept, was first raised in 1970s and it was used as a method for measuring the quality of healthcare (10). analysis of preventable death (pd) may aid in developing strategies for reducing mortality, improving quality of care, identifying new therapeutic strategies, applying advanced equipment, and enhancing training and technology (10, 11). this will also play a significant role in policy-making and care planning in the prehospital phase (4). given the absence of a systematic approach in preventing the injuries and victim management after rtis and obscurity of the weaknesses and strengths of prehospital emergency care in iran, this study aimed to identify the current challenges that affect the preventable deaths management in the prehospital phase based on the stakeholders’ experiences. 2. methods 2.1. study design and setting this qualitative conventional content analysis study was carried out from march 2018 to november 2018. at first, the research goals and procedures and interview methods were elucidated to the participants who were assured of voluntary participation. they were assured of information confidentiality and anonymity of the participants and their official post or responsibility. the informed written consent form was signed by the participants regarding interview recording. they could withdraw from the study at any stage. 2.2. participants the study participants included experts and specialists at the national level including the ministry of health and medical education, and also at the provincial level of yazd province, iran. the participants either had practical experience or theoretical knowledge on rtis. they had at least five years of experience in rti management in traffic police, the red iranian crescent, fire-fighting organization, ems, emergency medicine specialty, or hospital emergency nursing. participants’ selection started and continued with purposive sampling method till data saturation was reached. 2.3. data collection the first two interviews were carried out by means of unstructured in-depth interviews followed by 22 semistructured interviews. the interviews were commenced by the open-response question covering: “what’s your opinion about preventable deaths in rtis?” the follow-up questions were presented based on the feedback given by the participant and to clarify the concept under study. the items in the subsequent interviews were based on the concepts extracted from the data analysis. some exemplar questions were: “what factors reduce the preventable deaths in rtis? what strategies may be offered to reduce preventable mortalities in rtis? in your opinion, what’s the role of various organizations in decreasing preventable deaths in rtis?” the interview time was minimally 30 minutes and maximally 90 minutes with a mean time of 60 min. the interviews were first recoded digitally, and then transcribed verbatim on the same day using word office 2007. 2.4. data analysis the digital voice files were listened to several times and the transcriptions were completed. next, the interviews were reviewed several times and the meaning units were prepared. subsequently, similar codes were merged and analysis units were reviewed several times and classified on the basis of the similarity and difference of conceptual and meaning. the codes with similarities were categorized together. each time, the required modifications in the content and name of the category were done according to the item content. finally, the researchers and experts agreed on the meaning of data, subcategories and main categories. the extracted subcategories were classified into larger categories until the main categories had emerged. 2.5. trusthworthiness in this study, the guba & lincoln criteria (12) were used to increase data accuracy and rigor. therefore, the four criteria of guba & lincoln (1994), including credibility, transferability, dependability, and confirmability were taken into account by the researchers during the study process. to assure of the credibility, the researcher was in contact with the participants for a long time. moreover, an attempt was made to select the participants with respect to their knowledge, experiences, work experience, work places, age, and gender. increased dependability was achieved through step-by-step data collection and analysis and enjoying the reviews by experts and specialists. furthermore, to enhance dependabilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e32 table 1: baseline characteristics of participants variables number (%) age (year) < 40 4 (17) 40-50 13 (54) > 50 7 (29) gender male 15 (63) female 9 (38) education level associate diploma 2 (9) bs and msc 7 (29) phd/specialist 15 (62) work experience < 15 4 (17) 15 3 (13) >15 17 (71) bs: bachelor of science; msc: master of science; phd: doctor of philosophy. ity, the reflectory commentary were repeated and the details were recorded. to ensure confirmability, the participants’ opinions were checked to confirm the accuracy of codes by means of member check. if there was any mismatch between the codes and the participants’ opinions, the required corrections were made. furthermore, the dyadic control was done by two faculty members and experts in qualitative studies (d. kh; kh, n.) and agreement was achieved on the distilled codes and categories. to make sure of transferability, the details of the study were mentioned. finally, to establish confirmability, investigator triangulation was also used for checking the codes sub-categories and categories. 2.6. ethical considerations this study was part of a phd thesis in health in emergencies and disasters that was approved by ethics committee of at shahid sadoughi university of medical sciences with ethics code no.: ir.ssu.sph.rec.1397.038 dated 18.6.2018. 3. results a total of 24 experts aged 31-55 years were interviewed (62.5% male). baseline characteristics of participants are given in table 1. the official posts of the participants included: traffic police, red crescent staff, fireman, ems technician/staff, ems specialist, emergency nurse, specialist in health in disasters, and coroner or forensic medicine specialist. six main categories were extracted as the major challenges of preventable deaths in rtis in the prehospital phase including “poor management of the crash scene” with two subcategories of lack of rapid access to patient and lack of scene safety, “lack of adequate rules and regulations” with two subcategories of lack of protocols and guidelines and lack of clear duties checklists, “poor management of time” with two subcategories of elongated response time at the crash scene and elongated time of victim transport, “low quality of training” with two subcategories of insufficient training of ems staff and inadequate public training, “poor communication and coordination” with two subcategories of poor communication of ems staff and lack of uniform commandership at the crash scene, and “low quality of victim management” with two subcategories of low quality of clinical care and lack of accurate clinical assessment. table 2 presents the main categories and subcategories of challenges influencing preventable deaths in rtis in the prehospital phase on the basis of participants’ opinions in iran. 3.1. poor management of the crash scene lack of rapid access to patient before the rescue team arrives at the scene, the victim should be made ready for intervention and the rescuers or first aiders only perform an initial assessment of the victim and provide the required care instead of wasting their valuable time in anticipating for other organizations to place the victim in the appropriate situation. therefore, all interventions for victim preparation should be done before the rescue team arrives. in the participants’ viewpoints, the prompt attendance of red crescent staff at the crash scene, having standard equipment and facilities, and sufficient skill and experience in disentangling the victims are among the factors that play an important role in quick preparation of the victims for prehospital emergency interventions. p21: “. . . sometimes a car overturns in a road accident and is demolished, but when i arrive at the crash scene as an ems technician, i can see that the red crescent has not been able to untrap the victim out of the car wreckage. they really need training and expertise . . . ” 3.2. lack of scene safety the participants believed that lack of scene safety can serve as an influential challenge affecting the management of preventable deaths in rtis. though establishing the scene safety has been rendered as the duty of the police, in some cases the quarrel between people and the rescue team, people and the police, or the rescue team and the police has impaired scene safety leading to tension at the crash scene. lack of prompt presence of the police at the crash scene and occasionally lack of familiarity of the police with their duties or absence of shared understanding between the police and ems staff have caused tension at the crash scene, negatively affecting ems performance and thus hindering the immediate care-giving at the crash scene. prehospital emergency care-giving environment is stressful itself and affects ems performance. in addition, people get anxious on the crash scene, they observe the victims and give some advice to ems staff about carethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. eftekhari et al. 4 table 2: challenges affecting the management of preventable deaths due to road traffic injuries in the pre-hospital phase based on the participants’ opinions in iran categories subcategories code examples low quality of low quality of clinical care -wrong intubation victim management -insufficient fluid therapy of patients -not using cervical collar for the victims lack of accurate clinical assessment -inadequate report of medical history of patients to the hospital by technicians -incomplete clinical examination of the patients by technicians -unsuitable diagnosis of clinical status due to negligence in victim survey poor management of lack of rapid access to patient -lack of prompt presence of staff of the red crescent at the scene the crash scene -lack of sufficient skills in red crescent staff for rapid releasing of the victim -lack of adequate equipment for the red crescent staff in releasing the victim lack of scene safety -necessity of supervision on ambulance equipment to prevent robbing of equipment by bystanders at the scene -lack of proper cooperation of the police to prevent quarrels at the crash scene -physical fight between angry people and ems technician at the crash scene poor communication poor communication of ems staff -deficiency of communication infrastructures and coordination -necessity of teamwork by prehospital rescue team lack of uniform commandership -indecisiveness of the rescue team at the crash scene at the crash scene -irrelevant interference and assertions by different bystanders at the crash scene -dominance of the police over the crash scene most of the time lack of adequate lack of protocols and guidelines -necessity of reviewing the educational curriculum of medical emergencies major rules and regulations -necessity of assessing educational needs of prehospital rescue team -the need for use of experienced and tactful staff in prehospital emergency care -necessity of continuous and up-to-date education of the staff providing prehospital emergency care lack of clear checklists for duties -necessity of providing public education for dealing with road traffic injuries -lack of familiarity of the public with first aid principles -secondary damage to the victims by wrong interference of irrelevant individuals at the crash scene poor time management elongated response -time-consuming path to the crash scene due to unfamiliarity of the staff with uncrowded routes time at the crash scene -lack of collaboration of people in opening the way for the ambulance -lack of management of the police to avoid pile-ups at the crash scene elongated time of victim transport -wandering of ambulances at the crash scene due to lack of exit path for ambulances -not opening the road for ambulances by people from the crash scene to the hospital low quality of training insufficient training of ems staff -necessity of revising educational curriculum for ems major -necessity of assessing needs of prehospital ems staff -necessity of using skilled and tactful clinical staff in prehospital emergency care -necessity of up-to-date training of prehospital rescue team inadequate public training -necessity of providing public education on proper approach to road accident victims -unfamiliarity of the public with first aid principles -secondary damage to the victims due to the wrong interference of irrelevant individuals ems: emergency medical service. giving; however, this impairs the ems staff’s concentration adding to the stress governing them on the crash scene. that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e32 is why the police force should provide suitable conditions for the rescuer organization so they can give the necessary primary care as fast as possible and transport the victim. since the police are the prime managers of the scene safety, they must perceive the effect of the critical condition on the ems staff and control the bystanders at the crash scene without any quarrel or involvement. on the other hand, the medical and emergency equipment or materials in the ambulances are sometimes stolen at the crash scene by the passersby indicating lack of safety at the crash scene. p12: “. . . when we arrive at the crash scene, we face some angry people; i just think they’re right and their anger is justified; yet, it’s the duty of the police to manage the people and take them away from the scene of the injury. they should provide a safe scene for me to work properly and avoid pileups by stopping the traffic at least 200 meters away from the crash scene. however, the police sometimes do not engage themselves and i have to work under so much stress . . . ” 3.3. lack of adequate rules and regulations lack of protocols and guidelines lack of comprehensive protocols and guidelines in all areas related to prehospital ems (managerial and therapeutic) of rtis has been mentioned by the participants as another major challenge affecting preventable mortalities of rtis. there are no clear-cut guidelines for many cases like management of first aid bases, care-giving to traumatized patients in the hospital and prehospital phases, as well as guidelines of common act and extra-organizational communication. the participants have rendered as necessary the obligation for revising guidelines and protocols and updating them and also development of offline protocols for various situations to facilitate the decision-making of the responding staff. the offline protocols are required for performing any therapeutic interventions or managerial control in the prehospital phase. these offline protocols are needed for uniform and standard scientific treatment and care-giving and promotion of high quality care in ems missions. p17: “. . . we need protocols, especially for atls and ptls, which we have no protocols for; even hospitals don’t have these protocols. the staff members need guidelines showing them what to do, for example, if communication was cut off, i mean the offline protocol . . . ” 3.4. lack of clear duties checklists the participants believed that a detailed checklist of duties in the prehospital phase of rtis was necessary for each organization to indicate the role of each organization in case of injuries. this issue has been largely ignored by the authorities. indeed, obscurity of roles and duties of organizations (the red crescent, the police, and the fire-fighting organization) can, in its own account, serve as an influential challenge affecting preventable deaths. when a number of organizations agree to achieve a common goal, an important thing to do is proper management of those systems and determining their duties. given the sensitivity of the concept of time in the crash scene, the detailed identification of duties will be very influential, which if left unnoticed, it will result in parallel work. p9: “. . . when a force comes to the crash scene, they should be aware of their duties and oriented with them. many times we’ve entered the crash scene and observed that the police don’t know what to do . . . ” 3.5. poor time management elongated response time at the crash scene the participants stated that the time of arrival of ambulance at the crash scene of rtis and initiation of therapeutic interventions for the victim are highly important in avoiding preventable rtis deaths. however, they believed that victims do not receive the required treatment even in the case of preparation for giving high quality care due to reasons such as shortage of civil ems bases, the route traffic jam, lack of special route for rescue cars, and underdeveloped air ambulances. the prehospital rescue staff believed that if the green ring way, i.e. the shortest route for reaching the crash scene, is not announced by the police, this makes the ems staff to select the route themselves occasionally leading to selection of a wrong route with high traffic jam. the participants stated that the pile-ups near the crash scene where drivers stop their cars to film the crash scene or victims inquisitively elongates the access time for the prehospital ems staff. opening the route to the crash scene should be done by the police; however, the ems staffs face a crowded crash scene with much pile-up due to disorientation and negligence of the police. p17: “. . . sometimes, there is much traffic jam in the city and drivers do not pay attention to the ambulance siren, so, we have to take short-cuts to reach the crash scene sooner. yet, very often we face some problems in those short-cuts. suppose you are facing a crash scene in the crowded tehranqom highway. there is traffic jam 4 km before and 4 km after the crash scene; how can i reach the crash scene to access the victim . . . ?” 3.6. elongated time of victim transport another subcategory of poor time management is elongated time of victim transport. delay in announcing the injury to the hospital, delay in arrival at the hospital, and delay in delivery of the victim to the hospital are challenges that affect the rate of preventable deaths in rtis. the ems staff should deliver the victim to the hospital emergency physician along with the required medical history. however, when the prehospital emergency staff members arrive at the hospital, they should wait a long time to deliver the victim to the emergency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. eftekhari et al. 6 physician, although the critically ill victim is in the ambulance or on the stretcher in the emergency department. this is due to the fact that they give priority to other victims in the triage and ignore the rti victims. p13: “. . . when we take the victims to the hospital and want to deliver them, we wait a long time and no one is responsible . . . ” each ems system has a physician called the guide physician who is legally responsible for the clinical aspects of patient care. the therapeutic interventions performed in the prehospital emergency care are done by the permission of this guide physician. when there is a critically ill victim in the crash scene and the ems staff has to receive the required instructions from the guide physician via the wireless, a 1-second delay in responding may lead to victim’s death. from the participants’ view, prompt and effective responding of the oncall physician in appropriate provision of clinical care is directly related to the victim and any delay in the on-call physician’s response interrupts care-giving to the victim. p13: “. . . it has happened quite often that we called the oncall physician, but nobody responded; in many places, our wireless or cell phone had no signal . . . ” 3.7. low quality of training insufficient training of ems staff the participants asserted that training is one of the important factors in increasing skillfulness and tactfulness of ems staff; however, there are some significant challenges in this regard. challenges, such as lack of attention to comprehensive training during the retraining courses, lack of accurate assessment of requirements in line with the prioritized cases needed by ems staff at the crash scene, and absence of continuous educational evaluations for the staff has caused the ems staff to not possess the required skill and ability to give proper clinical care on the crash scene. p6: “ . . . some of the retraining courses held in the system are not useful for us; we just join such classes for their educational points and privileges . . . ” the employment of the staff in prehospital emergency care unit should be done on the basis of certain educational frameworks and rules. recently, the lack of any educational monitoring system for the employment of ems staff has led to the employment of staff with various academic degrees, such as phlebotomist, nurse, associate diploma/bs of ems, and 6-month trained technicians. this has led to a gap between knowledge and skills among the staff; therefore, each group needs to receive suitable educational services. p8: “ . . . 6-month trained staff who have no sufficient knowledge and skill in care-giving to victims are employed. this causes secondary damage to victims in some occasions . . . ” 3.8. insufficient public training the participants believed that sometimes lack of sufficient knowledge among people, performing the wrong interventions before the ems arrives at the crash scene and improper measures during care-giving imposes irreversible damages on the victim indicating the importance of training for the public. sometimes, the intervention done for the victim by the first bystanders in the crash scene enhances the performance of ems staff; nevertheless, many times such interventions lead to more severe damage to the victim that may be irreversible. from the prehospital emergency care staff’s viewpoint, public training in areas like medical emergencies, making contact with ems facilities, and anything required for primary treatment of the victims ought to receive special attention. p7: “. . . we had a victim on the crash scene with a great amount of blood in the throat. people at the scene did not know that a simple change of position may remove the secretions, clear his airway and save him; unfortunately, the victim died . . . ” 3.9. poor communication and coordination poor communication of ems staff from the participants’ perspective, proper communication between the staff during performing duties is always important in achieving the intended result. factors, such as poor communication between ems staff, between ems staff and red crescent staff, and between police and fire station staff serves as an influential challenge affecting the preventable deaths in rtis. absence of a common jargon among the ems staff, lack of agreement on priorities and concepts, weak infrastructures and communication equipment, and lack of communication paths were mentioned as major obstacles in the way of rapid and efficient communication. p10: “. . . the police can communicate with ems system, but i can’t access them since this communication is unilateral. in many occasions, there has been the need for communication yet, i didn’t have any access to police . . . ” lack of uniform commandership at the crash scene absence of uniform commandership at the crash scene was mentioned as one of the effective challenges in care-giving to victims from the participants’ perspective. lack of integral commandership at the crash scene makes the forces function diversely as separate islands without any coordination among them leading ultimately to low quality care. different people at the crash scene order the prehospital ems staff with their dos and don’ts or musts and mustn’ts; while there are sometimes obvious contradictory orders. sometimes, the involved organizations do not show much compliance towards each other predisposing to indecisiveness of the forces. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e32 p14: “. . . everybody at the crash scene states their own opinion with nobody there to obey them. they all want to say that their opinion is correct . . . ” 3.10. low quality of victim management low quality of clinical care the prehospital emergency care staff believed that the type and priority of the provided care, promotion of quality care, and its warranty are of utmost importance; therefore, they asserted that the mere provision of care would not suffice; this care ought to be given with proper quality and via observation of professional knowledge too. they also stated that the provided care sometimes does not possess the required quality in the prehospital phase and negligence in care provision at the crash scene or during victim transport is an important challenge itself in managing preventable deaths in prehospital emergency care. p8: “. . . .it has happened several times that when i received the victim from the prehospital care team, i saw that the ivline placed for the patient was, in fact, subcutaneous or i observed several times that they had tried to perform intratracheal intubation for the patient, but they did intraesophageal intubation . . . .” lack of accurate clinical assessment from the participants’ viewpoints, inappropriate assessment of the clinical condition of victims on the crash scene or during transport and absence of subsequent accurate evaluations at the time of delivery of the victim to the hospital or inadequate victim examination by the physician play a significant role in increasing preventable deaths in rtis. some prehospital care staff members believe that a rapid and simple cephalocaudal examination of the patient should be done leaving the complete examinations for the hospital emergency and physicians. rapid transport of the patient to hospital is important; however, the sufficiency of prehospital emergency interventions on the victim is also important. the patient’s condition ought to be assessed thoroughly; otherwise, any negligence may predispose the patient to death. p7: “. . . when the victim is brought in by the technician and i ask him/her . . . .about their clinical condition, i see that he/she is not aware of it; for example, he/she does not know their score on glasgow coma scale or where in the body the patient has trauma. they can’t answer my questions; then i understand that they have not checked the victim sufficiently . . . .” 4. discussion this study investigated the managerial challenges of preventable deaths in rtis in the prehospital phase. it was indicated that the prehospital phase of rtis suffers from deficiencies like low quality of victim management, poor management of the crash scene, shortage of communication and coordination, lack of required rules and regulations, poor management of time, and low quality of training. paying attention to these challenges would lead to provision of high quality care to victims in the prehospital phase. conventional content analysis is a suitable method for obtaining valid and reliable results using transcribed text data. it creates knowledge, new ideas, and facts and serves as a practical guide of performance (13). it may prove useful in deep recognition of challenges affecting preventable deaths in rtis in the prehospital phase. one challenge found in this study that affects the management of preventable deaths in rtis was low quality of clinical care and lack of accurate clinical assessment of the victims in the prehospital phase. suitable primary care for traumatized victims on the crash scene and during transport improve the poor prognosis of the victims by itself, although it has been proved to be effective in decreasing the severity of damages to the victims (9, 14-17). interventions like airway management, intubation, and chest tube placement are considered advanced care on the crash scene (18). in a study that investigated the quality of prehospital care for traumatized patients referred to emergency of a hospital in tehran, wound dressing and hemostasis were performed correctly in 80% of cases. splint was also applied correctly in 50% of cases while interventions, such as cervical collar and spinal bed were not performed in 80% of cases. furthermore, although the ems staff had placed an iv-line in 91.2% of cases, no serum was infused to the victims in 80% of cases (19). prehospital emergency care should be not only rapid, but also accurate and precise (20). indeed, appropriate interventions on the crash scene are one of the cornerstones of prehospital emergency care. high quality care-giving is the main factor in saving humans’ lives, which is considered the best outcome. another challenge postulated by the participants was the lack of accurate clinical assessment of the victims in the prehospital phase of rtis. joshipura et al. enumerated 12 priorities as care priorities in injuries, including team formation, airway investigation, respiration, blood circulation and shock, diagnosis and monitoring, head and neck injuries, chest and abdomen, upper and lower extremities, spinal cord, burns and injuries, pain control, rehabilitation, and infection control each of which ought to be prioritized depending on the type of rti (21). providing optimal care for victims and determining life-threatening conditions demand accurate evaluation. precise clinical evaluation is one of the most important ways of obtaining vital information on the victims, which is unfortunately ignored most of the time or performed hastily. in fact, prehospital emergency care deals with making decisions about treatment and transport. the victim assessment data are the guiding factor for ems staff in their decision-making at the crash scene. the staff should perform a primary assessthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. eftekhari et al. 8 ment of the vital signs of the victim or any life-threatening factors after they are assured of the safety of their location and safety of the victim. this assessment ought to be highly accurate so that it can completely identify the status of the victim when the diagnostic data are conveyed to the on call physician. poor management of the crash scene was another influential challenge affecting the preventable deaths in this study. poor management is one of the current challenges of rtis in iran. in this study, delayed access to victim was one of the challenges that affected deaths related to rtis. this factor is influenced by factors, such as crowded pile-up and closure of access route to the crash scene. passerbys’ intervention at the crash scene either facilitates or debilitates preventive care in rtis (22). the public presence at the crash scene due to personal curiosity, enthusiasm for humanistic help, excitement, and haste result in a crowded pile-up and poor communication (23). providing primary emergency care on the crash scene and during victim’s transport to hospital help to improve victim’s prognosis by itself. who recommends scene safety for road accident victims (9) as the primary intervention (24). various organizations collaborate at the crash scene to achieve the common goal of saving the victim’s life. the red crescent staff members are among the first aiders who should be present at the crash scene as securers of scene safety before the ems staffs arrive. they should prepare the victim for receiving care. considering the importance of time and the urgency of performing therapeutic interventions for victims, the crash scene should be set in a way that provides immediate victim access for prehospital ems technicians. the situation should be adjusted by the red crescent staff that arrives at the crash scene before the ems staff, so that the ems staff can have access to victims once they arrive there. moreover, some studies have demonstrated that illogical and irrational public pile-up at the crash scene elongates the course of care-giving to victims and reduces safety (9, 25, 26). the crowd wastes the critical time needed for prompt care-giving and may even induce secondary damages and even cause new injuries (27). lack of proper communication and coordination was another variable affecting preventable deaths presented by the present study. suitable communication and coordination can increase readiness for prehospital care provision (17, 28). lack of coordination in the healthcare system has led to improper allocation of budget to healthcare and deprivation of patients form adequate care (15). a balance should exist between human resources and communication equipment. the victim shall receive optimal care when there is a close contact among all emergency care providers. the public crowd at the crash scene doubles the stress, which leads to reduced collaboration among the ems staff and hinders sharing of experiences for performing therapeutic interventions on victims and controlling the crash scene. another factor required for coordination between the ems staff and physician is the presence of appropriate equipment. the use of a widespread communication system, creation of an effective direct wireless system, and working with a uniform frequency for all administrative and supervising respondents at the crash scene are mandatory. lack of a uniform commandership system is another factor related to the shortage of communication and coordination needed for proper management of preventable deaths in rtis. depending on type of injuries, various organizations attend the crash scene; hence, there ought to be a uniform comprehensive system of commandership to manage the scene with due power. the accident commander should act in a way that enables him/her to actively manage all of the traffic trends during the accident till the situation returns to normal. the police have been introduced as the coordinating element in managing rtis as well as factors that influence crash scene management (29, 30). the accident commander may vary depending on the type of accident. nevertheless, the important point here is that, due to the presence of different organizations, the commander can be selected on the basis of injury type through developing the required processes and guidelines. another challenge identified in this study was the lack of rules and regulations, which brings about indecisiveness in care-giving by ems staff and sometimes performance of incomplete or repetitious interventions due to absence of checklists for duties. additionally, another challenge in prehospital emergency care was the presence of diverse guidelines and protocols without considering clinical evidence. the presence of developed protocols and guidelines are deemed mandatory for promoting communication, better clinical care, and the subsequent decrease in rti mortality (31). lack of evidence-based protocols and guidelines would lead to lack of standard clinical care provision and disintegration of communication and coordination process in management of the crash scene, resulting in increased preventable deaths in rtis (26). on the other hand, the present protocols mostly emphasize the monitoring of victims with few of them dealing with clinical care provision (32). today, one of disasters of prehospital emergency care is the lack of checklists for duties of each organization involved in rtis. when a number of rescue organizations join together to achieve a common goal, proper organization of these systems and determining the details of their duties are obligatory. various systems such as the police, emergency service, the red crescent, fire fighting organization, etc. collaborate with each other depending on the type of injury. in so doing, they require a checklist of duties for each organization to both prevent interference and enable each to recognize its own duties on the basis of the present conditions. the present study rendered poor time management as an important challenge in prompt clinical care provision to rti this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2019; 7 (1): e32 victims. in this regard, elongated response time and transport time are considered as important challenges of time management. the kind of response by bystanders at the crash scene influences the ems response time. the findings of previous studies suggest that reduced time at the crash scene improves the outcome of rti victims (26, 33). exploration of the status of traumatized victims in the prehospital emergency care reveals that the response time in rtis has decreased in iran and the emergency care approaches the global standards in most iranian cities except tehran, the capital (34, 35). despite the fact that time at the crash scene for stabilizing the traumatized victims would improve their prognosis (36-39), the american college has recommended that the stay time at the crash scene should be reduced as much as possible (33). earlier coordination between the prehospital and hospital emergency care units is one of the influential factors that decreases the victim transport time and enhances the treatment team’s preparation for proper caregiving (40). one of the most influential factors affecting the standard response time is a crowded access route since the current traffic jam attenuates the efficacy of ambulances and their fast performance. this causes the response time to exceed the standard limits. heavy traffic jam is reported as one of the reasons of elongated response time in other studies (41, 42). the use of motorcycle ambulance and air ambulance is recommended for quick transportation of victims from the crash scene to the hospital emergency care indicating the importance of saving human lives. another factor leading to an elongated ems response time is the long distance. if the ambulance driver is not familiar with the short-cut routes, they will certainly arrive late at the crash scene. some strategies such as the technician’s familiarity with short-cut routes, the use of satellite path-finder systems, radar, gps, and high frequency waves for finding the best route in emergency cases can help in this regard (42). of course, it should be kept in mind that finding the shortest route is not always possible and sometimes a low traffic but longer route with higher speed can be more helpful. another challenge extracted in this study was the lack of effective training of ems staff and the public as the first responders at the crash scene for reducing preventable deaths in rtis. it is highly important to plan suitable educational programs on preventing rtis and quick response to them. assessment of needs should be prioritized first, followed by dynamic training and updating staffs’ knowledge in a concentrated framework of management and organization. in a study conducted on assessing educational needs of ems technicians, most of them pointed to knowledgeablility followed by pharmaceutical information and drug complications. regarding skills, they pointed to skillful intratracheal intubation, and with respect to attitudes, they pointed to participation in in-service continuous educational courses for promoting their practical skills (43). topics on prehospital emergency care such as crash scene assessment, identification of work groups in emergency room (er), identifying details of patient examination, and triage ought to be covered in the syllabus of wouldbe rescuers such as students of nursing or ems (44). use of simulation in the virtual form or using a computer or online method in a recreated environment will be helpful in improving the victim’s management on the crash scene, increasing the ability of scene management, and enhancing decisionmaking. moreover, the use of “standard patient” will be beneficial in training the staff on how to treat traumatized patients with internal problems, or symptoms of special disorders. even role playing can help in training and creating the feeling required for the role of learners to approach patients under different conditions. holding practical classes during the education years may positively influence the volunteers of working in emergency wards. these classes should be held on the victims’ bedside to be more efficient (45). to train the ems staff, emphasis should be on experienced instructors, revision of educational classes, and the use of practical methods of training wile also considering the results of assessment of needs and the quality of interventions. furthermore, ems bases should be equipped with educational technology such as moulages, tv and video players, along with teaching materials like pamphlets, books, booklets, etc. the important topics to be covered in prehospital emergency care syllabus include crash scene assessment, identification of work groups in emergency care, identification of details of patient survey, and triage (46). provision of the required training in clinical skills will promote the work quality of ems staff and other organizations involved. avoiding first aid provision by the public and lack of training in this regard was found to be another important challenge in this study. training should be based on the specific needs of each community and the available resources. training should use simple local language and focus on transferring vital skills of crash scene management, hemostasis, primary cardiopulmonary resuscitation (cpr), handling and transporting the victim with open fractures, and triage. the acquisition of these skills by these learners, is highly efficacious immediately after injuries in the absence of healthcare experts. a study on prehospital emergency care obstacles conducted in lmics (2018) reported lack of training as one of the known obstacles in the way of better care provision in the prehospital phase (15). moreover, public education regarding the crash scene and the acquisition of first aid skills for improving victim outcomes in the prehospital phase are mentioned as effective factors (35, 44). the role of bystanders as primary helpers at the crash scene has been emphasized (17). some countries like india plan and implement special courses for training the public for medical intervention in emergency scenes (23). indeed, development of public education in first aid at this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. eftekhari et al. 10 the crash scene is mandatory. of course, direct provision of first aid will not work without preparing the cultural background and infrastructures. then public would wish to learn and the healthcare system would inform the public about the importance of saving lives. 5. limitation the limitation of this study was that it was difficult to coordinate interviews with experts. time limitations were other limitations of the study. persistent attempts by the researcher resolved this issue to some degree. 6. conclusion the participants’ experiences about challenges that influence management of preventable deaths in rtis showed that, in order to improve management of possible deaths resulting from it, consideration of issues such as accurate clinical assessment of the victim on the crash scene without any negligence, provision of high quality care, the presence of required legal obligations and protocols for treatment and management, coordination of the involved organizations through identifying detailed duties for each, and full management of the crash scene via determining a uniform and unique commander and creating the highest level of scene safety are essential. the authorities should take into account the scientific knowledge and practical skills of ems staff, and public first aid training regarding the crash scene. 7. appendix 7.1. acknowledgements the authors wish to thank shahid sadoughi university of medical sciences for financially supporting this study. moreover, they would like to express their gratitude to all participants who spent their precious time contributing to the scientific richness of this study. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. adel eftekhari, davoud khorasanizavareh and abbasali dehghani tafti designed research; adel eftekhari conducted research; khadijeh nasiriani, majid hajimaghsoudi and hossein fallahzadeh analyzed data; and adel eftekhari and davoud khorasani-zavareh wrote the paper. davoud khorasani-zavareh has primary responsibility for final content. all authors have read and approved the final manuscript. authors orcids adel eftekhari: 0000-0001-7961-2699 abbasali dehghanitafti: 0000-0002-7040-4188 khadijeh nasiriani: 0000-0003-3600-9456 majid hajimaghsoudi: 0000-0002-2699-4846 hossein fallahzadeh: 0000-0001-9443-6208 davoud khorasani-zavareh: 0000-0001-6265-8148 7.3. funding/support this paper is part of a phd dissertation in “health in emergencies and disasters”, which was financially supported by shahid sadoughi university of medical sciences, yazd, iran. 7.4. conflict of interest the authors declare that there is no conflict of interest with respect to the research, authorship, and publication of this article. references 1. world health organization. global status report on road safety 2013: supporting a decade of action: world health organization; 2013. 2. world health organization. 10 facts on global 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midwifery faculty in 2005. proceeding of the 3rd international congress of cure and health and crisis management in disaster 2001; iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e7 or i g i n a l re s e a rc h workplace violence against residents in emergency department and reasons for not reporting them; a cross sectional study gilava hedayati emam1, hossein alimohammadi1, akram zolfaghari sadrabad2, hamidreza hatamabadi1,3∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam reza hospital, school of medicine, kermanshah university of medical sciences, kermanshah, iran. 3. professor of emergency medicine, safety promotion & injury prevention research center, injury prevention & trauma network, shahid beheshti university of medical sciences, tehran, iran. received: december 2017; accepted: december 2017; published online: 16 january 2018 abstract: introduction: due to the stressful nature of emergency department (ed), residents in ed are at risk of violence from patients or their associates. this study aimed to determine the prevalence of workplace violence against ed residents and the reasons for not reporting them. methods: this cross-sectional study was conducted on ed residents of three educational hospitals, tehran, iran, during 2015. the national questionnaire about workplace violence was used for data gathering. in addition, prevalence of reporting the violence and the reasons for not reporting them were determined. results: 280 questionnaires were analyzed. the mean age of residents was 32.2 ± 4.6 years (58.4% female). 224 (80%) residents stated that they had not passed any educational courses on violence management. the most prevalent type of violence was verbal (90.7%) and patients’ associates (85.4%) were the most common source of aggression. the frequency of physical violence was higher in male aggressors (p = 0.001), resident age > 30 years (p = 0.044), aggressor age > 30 years (p = 0.001), and night shift (p = 0.001). the same trend was observed regarding verbal and racial-ethnic violence. there was no significant relationship between residents’ sex, resident’s specialty, and presence of security and police with frequency of violence. 214 (76.4%) residents did not report the violence, and the main reasons for not reporting from their viewpoint were uselessness of reporting (37.4%) and insignificance of the violence (36.9%). conclusion: based on the findings of the present study more than 90% of ed residents had experienced at least one type of verbal, physical, or racial-ethnic violence during their shifts. it is necessary for residents in eds to be trained about violence control and also report and follow these issues through legal channels. keywords: workplace violence; physical abuse; internship and residency; emergency service, hospital © copyright (2018) shahid beheshti university of medical sciences cite this article as: hedayati emam g, alimohammadi h, zolfaghari sadrabad a, hatamabadi h. workplace violence against residents in emergency department and reasons for not reporting them; a cross sectional study. emergency. 2018; 6(1): e7. 1. introduction w orkplace violence, which involves physical, verbal, cultural, racial-ethnic and sexual violence, is a worrying issue for every person in every workplace and its trend is increasing (1-3). world health organization (who), in its first world report on violence and health, ∗corresponding author: hamidreza hatamabadi; department of emergency medicine, imam hossein hospital, madani street, tehran, iran. p.o.box: 193955487 fax: +98 2188067114 tel: +98 2181262073 email: hhatamabadi@yahoo.com described violence as: use of physical or mental power for threatening or acting against oneself, another, a group or community, causing injury, death, mental injury, retardation in growth or deprivation, or increasing the likelihood of these events. also, who estimates that nearly 1.6 million people annually die because of violence worldwide (4-6). recently, workplace violence in health system has become an important issue in policymaking and it is one of the most important and complex issues in the health system. the hospital staff, including nurses and physicians, are at greater risk of workplace violence (7). the probability of workplace violence for health workers and particularly nurses is even this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com g. hedayati emam et al. 2 higher than prison guards or police officers (8, 9). the most important subsequences of violence against health workers are increase in awful incidents, the cost of retention and employment, absenteeism, tardiness and job abandonment, avoiding patients, patients’ complaints, job burnout, and mental exhaustion and also decrease in the efficiency and job performance of healthcare staff (10). insults and violence at the time of providing health care for the patient not only jeopardize the physical, emotional and psychological status of the healthcare staff, but also distort the therapeutic relationship between them and patients, which ultimately results in these adverse effects having negative influence on patients’ health (11). in the emergency department (ed) its stressful nature and direct contact with patients and their associates increase the likelihood of violence against health workers. disease stress, patient pain, and high latency for doctor’s arrival or receipt of medication and pain relief are some factors that can exacerbate violence against ed personnel (12). despite the overcrowding of ed and the unresolved issues of emergency patients, which contribute to the rise of violence in ed, the importance of this issue has not yet been widely acknowledged in iran. it is necessary to determine the nature and causes of this violence in order to be able to plan and make policy in this regard to provide safety for healthcare staff and improve health services for patients. therefore, this study attempts to determine the prevalence of violence from patients and their relatives to ed residents and the reasons for not reporting. 2. methods 2.1. study design and setting this is a multi-centric, cross-sectional study that was conducted on ed residents of three educational hospitals affiliated to shahid beheshti university of medical sciences (imam hossein, shohadaye tajrish, loqman hakim) in tehran, iran. data collection was carried out from december 2014 to november 2015. the study followed the principles of the declaration of helsinki and was approved by the medical ethics review board of shahid beheshti university of medical sciences. all information about the residents was kept completely confidential, and all information is released as a group without participants’ name. study participants did not incur any costs and the study protocol did not cause any harm to participants. written informed consent was obtained from volunteers and details and purpose of the study were disclosed. 2.2. participants residents working in ed of the mentioned hospitals, who volunteered to participate in the study and had contact with patients were included. residents who were reluctant to participate in the study and those with incomplete questionnaires were excluded. 2.3. data gathering the sampling method was simple (consecutive) and residents in the ed were included in a voluntary manner. all the residents, either those who experienced violence or those who didn’t, were questioned using the national questionnaire about workplace violence in persian language. the questionnaire consisted of demographic data of ed residents (age, sex, marital status, average number of shifts per week, type of shifts), questions about occurrence of the verbal, physical, or racial-ethnic violence which caused by patients and their associates, and finally questions about the reactions of residents to violence and the rate of reporting violence cases and the reasons for not reporting the cases. for eliminating some cultural limitations of participants, questions related to sexual violence were deleted from the questionnaire. in a previous study, the validation of the national questionnaire about workplace violence has been determined and confirmed through its content validity and reliability (13). the correlation coefficient of the questionnaire was 78%. after obtaining ethical approval, the researcher (a senior emergency medicine resident) went to the eds for visiting residents on morning, evening or night shifts. the researcher described the study purpose, directions for participation, and information about informed consent for residents. then, distributed the printed anonymous questionnaires among the residents. residents returned completed questionnaires in provided envelopes, which were delivered to the researcher. it should be noted that, distribution and filling out the printed anonymous questionnaires were never done at the same time. 2.4. definitions: physical violence: use of physical strength against a person or group, including beating, kicking, slapping, using cutting devices, stabbing, shooting, firing, throwing an object, spitting, pushing, scratching, beating, pulling hair, pulling, pushing, hitting, grabbing, squeezing, twisting, punching, pinching or other similar things. verbal violence: behaviors such as intimidating, insulting, humiliating and patronizing actions, cursing, screaming, ridicule, cussing, bullying, yelling at or berating a person in front of another, slurring, and bullying that are repeatedly conceived. also, raising of fists and attempts at physical violence were defined as verbal violence. racial-ethnic violence: any harassment, humiliation, mockery, etc. due to ethnicity, race, language, religion and place of birth that affect human dignity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e7 table 1: baseline characteristics of the studied residents (n = 280) variables number (%) sex male 116 (41.6) female 163 (58.4) age (year) ≤30 116 (41.4) >30 164 (58.6) marital status single 111 (45.1) married 135 (54.9) postgraduate year level 1 82 (38.3) 2 76 (35.5) 3 56 (26.2) specialty * emergency medicine 56 (51.4) surgery 15 (14.2) orthopedics 11 (10.4) pediatrics 2 (1.9) internal 15 (14.2) neurology 3 (2.8) neurosurgery 4 (3.8) violence verbal 254 (90.7) physical 162 (68.6) racial-ethnic 25 (8.9) aggressor patients 164 (58.5) associates 239 (85.4) co-workers 32 (11.4) others 31 (11.1) *among those who reported their specialty, some ticked more than one item. 2.5. statistical analysis data analysis was done using spss version 17.0 (spss, inc., chicago, il, usa). data are presented as frequency and percentage for qualitative variables, and mean ± standard deviation for quantitative variables with a normal distribution. since all quantitative parameters had normal distributions according to kolmogorov-smirnov test, chi-2 test was used for comparison of continuous parameters. p values less than 0.05 were considered statistically significant. 3. results 3.1. baseline characteristics of participants 344 questionnaires were distributed among ed residents, after initial examinations and removing incomplete ones, 280 questionnaires were used for analysis. the mean age of these residents was 32.2 ± 4.6 (2747) years (58.4% female). table 1 shows the baseline characteristics of studied residents. it’s worth noting that in 171 questionnaires, the specialty of resident was not mentioned. 224 (80%) residents stated that they had not passed any educational courses on violence management. 3.2. violence against participants the most prevalent type of violence was verbal (90.7%) and patients’ associates (85.4%) were the most common source of aggression (table 1). the frequency of physical violence was significantly higher in male aggressors (p = 0.001), resident age > 30 years (p = 0.044), aggressor age > 30 years (p = 0.001), and night shift (p = 0.001). the same trend was observed regarding verbal and racial-ethnic violence (table 2). there was no significant relationship between residents’ sex, resident’s specialty, and presence of security and police with frequency of violence. 3.3. predisposing factors of violence lack of information about duties of residents among people (118; 44.7%), lack of security facilities (70; 26.5%), lack of training courses regarding violence prevention (44; 16.7%), taking psychedelic drugs or alcohol by patients (31; 11.7%), and lack of information regarding legal issues (23; 8.7%) were the most important predisposing factors of violence on the viewpoint of ed residents, respectively. 3.4. preventive factors of violence ed residents reported the presence of police (82; 29.8%), performing safety measures (65; 23.6%), the presence of security personnel (41; 14.9%), training the staff about violence management (25; 9.1%), restrictive measures such as penalties for aggressors (27; 9.8%), existence of instructions on dealing with violence (18; 6.5%), violence reporting system (16; 5.8%), and separating criminal patients from other patients (1; 0.4%) as the most important preventive factors of violence in ed, respectively. 225 (80.3%) of residents declared that participating in training courses on violence control and the existence of a management system for reporting and controlling violence are so important and necessary. 3.5. residents’ reaction to violence in response to all kind of violence, the most common reactions among residents were self-defense (78; 28.9%), invitation of attacker to relax (66; 24.4%), not taking any action (62; 23.0%), pretending nothing had happened (32; 11.9%), asking for help (15; 5.6%), sharing with colleagues (15; 5.6%), and sharing with friends and associates (2; 0.7%), respectively. 3.6. reporting the violence 76.4% of residents did not report the violence, and the main reasons for not reporting from their viewpoint were uselessness of reporting (37.4%), insignificance of the violence this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com g. hedayati emam et al. 4 table 2: correlation of physical, verbal and racial-ethnic violence with some variables variables physical p verbal p racial-ethnic p aggressor sex male 141 (78.8 ) 0.001 185 (77.4) 0.001 20 (83.3) 0.001 female 38 (21.2) 54 (22.6) 4 (16.7) resident age ≤30 72 (45.3) 0.044 92 (55.5) 0.001 11 (50.0) 0.983 >30 87 (54.7) 115 (44.5) 11(50.0) aggressor age ≤30 72 (37.5) 0.001 95 (37.4) 0.001 5 (20.0) 0.001 >30 120 (62.5) 159 (62.6) 20 (80.0) shift morning 42 (19.6) 51 (17.8) 8 (33.3) evening 47 (21.9) 0.001 67 (23.3) 0.001 4 (16.7) 0.015 night 125 (58.5) 169 (58.9) 12 (50.0) ∗ data are presented as estimated value and 95% confidence interval. lr: likelihood ratio. table 3: reasons for not reporting the violence from the viewpoint of emergency department residents reasons number (%) thought reporting was useless 80 (37.4) it was not important 79 (36.9) did not know where to report 33 (15.4) felt embarrassed 11 (5.1) blamed him/herself 11 (5.1) feared negative consequences 0 (0) (36.9%), and not knowing the source or system for reporting violence (15.4%), respectively (table 3). 4. discussion based on the findings of the present study, more than 90% of ed residents had experienced at least one type of verbal, physical, or racial-ethnic violence during their shifts. male aggressors, resident and aggressor age > 30 years, and night shift significantly correlated with higher frequency of violence. uselessness of reporting and insignificance of the violence were the most important causes of not reporting. the findings demonstrated that residents in ed were more likely to experience verbal violence (90.7%), because when patients or their associates are upset and in a stressful condition, they first show their anger as a verbal violence (insulting, ridicule, etc.), then they turn to threatening and finally show physical violence, which was 68.6% in current study. in ayranci study, in turkish eds, most participants had experienced verbal violence and subsequent physical threats and attacks (14). in a study in egypt, samir et al. reported that the most common violence against medical staff in gynecology department was physical violence with 78.1% (15). in the study by lavorie et al., eds of 127 educational hospitals with at least 40,000 visits per year in the state of kentucky were surveyed, and 32% of healthcare staff encountered at least one verbal violence per day, and 25% faced at least one physical violence per day (16). senuzum et al., reported 98.5% and 19.7% for verbal and physical violence, respectively (17). these studies are consistent with the current study and show a high prevalence of violence. in the present study, more than half of the violence had occurred on the part of patient’s associates (85.4%). this seems to be related to the unnecessary presence of the patient’s associates and their roaming in eds. also, the lack of a waiting room in eds creates more tension between health staff and patients’ associates. along with the findings of current study, salemi et al., (18) and rafati rahimzadeh et al. (19) also found that most violence came from the patients’ associates. ayranci’s study also found that the patient’s associates were the source of most of the violence in ed (14). contrary to the findings of the present study which demonstrated that more physical and verbal violence happened to residents with age more than 30 years, the results of cheraghi et al. stated that lower-age medical personnel were more at risk of experiencing verbal violence (20). in the present study, there was no significant relationship between resident’s sex and specialty with frequency of violence. yet, some previous studies have shown that in all parts of the hospital, female health staff were more often victims of physical violence (21, 22). also, male sex and age over 30 years in aggressors had a significant correlation with violence. consentient with these findings, previous studies showed that most violence was committed by men (23, 24). additionally, we found that night shift in eds is the most common time of violence occurrence, which confirms the findings of previous studies (1, 23). from the viewpoint of the ed residents in the present study, the main predisposing factors for violence in ed was lack of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e7 information about residents’ duties among the people and lack of security facilities. rahmani et al. showed that 67.4% of ems personnel mentioned lack of information about their duties among people as a main cause of violence in their workplace (25). meanwhile, in another study, ed nurses reported a lack of control over traffic of patients’ associates, lack of control on the number of patients’ associates and a lack of security staff as the most important factors that exacerbated workplace violence (26). a study in morocco showed that the main causes of violence against medical personnel includes delayed counseling and treatment in 52% of cases, being drunk in 17% of cases and mental illness in 5% of cases of violence (10). in the present study, police forces, safety measures in ed and the presence of security were mentioned as the most important factors preventing violence in eds. therefore, this indicates the need for supportive systems to protect victims of workplace violence. also, the most common reaction of ed residents was selfdefense, inviting aggressor to relax and taking no action. in another study on ems personnel, the respondents’ most frequent reaction to violence was inviting aggressors to relax (25). it should be noted that such collisions between emergency staff with patients and their associates eliminate mutual trust, and may lead to very unfortunate consequences. 76.4% of residents did not report the violence and uselessness of reporting from their viewpoint, low importance of violence and not knowing a source for reporting violence were the main reasons for not reporting violence. similar to current findings, other studies also indicated that most violence are not reported at all and cases were only reported if there was a physical impairment. also, some believe that facing the violence is part of their jobs and do not report them (3, 17, 18). in other studies, the greatest reasons of not reporting violence was the ineffectiveness of this report and neglecting the issue by the managers (20, 27). in the present study, most residents (80%) had not passed any training courses on violence control, and most of them asked for participation in training courses on violence control and expressed the need for a management system to report and control violence. in another study, only 22% of residents received formal or informal education on violence, and 81% of residents did not know how to report violence (23). also, gates et al., found that 64% of ems staff had not passed any training courses to prevent violence during the previous 12 months, and they asked for increased security and reduced violence, and stated that this would promote job satisfaction and health service efficacy (3). supervisors, managers and coworkers should not consider violence as part of residents’ job in eds, and ignore reporting of violence. a continuous training program for residents to use different and effective methods for coping with violence is recommended. also, accurate reporting of violence should be considered as a preventive measurement for violence, and managers must encourage staff to do so. it may be necessary to equip eds with a system for reporting violence to quickly identify the residents at risk and those who were hurt to take measures such as counseling and prevent more harm to residents and increase the quality of health care for patients. violence in eds could interfere with residents’ concentration during practice, increase the amount of medical errors, and result in losing a shift, frequent absences, disregard to the patient, loss of job satisfaction, worrying about work, refusal to attending in stressful conditions and even leaving the job, which impose a high cost on health care systems (28). 5. limitation this study has some limitations that restrict its application and generalization. first, these findings are based on selfreporting of residents. second, because of psychological effects, some residents may refuse to remember or report workplace violence, particularly racial-ethnic ones. third, residents were asked to report the occurrence of violence in the last 12 months, which could lead to bias in remembering. sexual violence was not investigated in this study, because according to the current culture of iranian society, most people do not talk about sexual issues and might have led to unrealistic data. 6. conclusion based on the findings of present study, more than 90% of ed residency residents had experienced at least one type of verbal, physical, or racial-ethnic violence during their shifts. male aggressors, resident and aggressor age > 30 years, and night shift significantly correlated with higher frequency of violence. uselessness of reporting and insignificance of the violence were important causes for not reporting. it is necessary for residents in eds to be trained about violence control and also report and follow these issues through legal channels. 7. appendix 7.1. acknowledgements the authors thank emergency departments of shahid beheshti university of medical sciences for facilities and technical assistance. the authors also gratefully acknowledge the cooperation of residents, without whom this investigation would not have been possible. 7.2. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com g. 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hospitals of medical universities in tehran. journal of shahid beheshti faculty of nursing and midwifery. 2012;22(77):32-8. 27. kamchuchat c, chongsuvivatwong v, oncheunjit s, yip tw, sangthong r. workplace violence directed at nursing staff at a general hospital in southern thailand. journal of occupational health. 2008;50(2):201-7. 28. adib sm, al-shatti ak, kamal s, el-gerges n, alraqem m. violence against nurses in healthcare facilities in kuwait. international journal of nursing studies. 2002;39(4):469-78. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 90 emergency (2014); 2 (2): 90-95 original research effects of intravenous fluid therapy on clinical and biochemical parameters of trauma patients shahram paydar1*, hamid bazrafkan1, nasim golestani2, jamshid roozbeh3, abbas akrami1, ali mohammad moradi1 1. trauma research center, shiraz university of medical sciences, shiraz, iran 2. emergency medicine department, isfahan university of medical sciences, isfahan, iran 3. nephrology ward, department of internal medicine, shiraz university of medical sciences, shiraz, iran abstract introduction: the administration of crystalloid fluids is considered as the first line treatment in management of trauma patients. infusion of intravenous fluids leads to various changes in hemodynamic, metabolic and coagulation profiles of these patients. the present study attempted to survey some of these changes in patients with mild severity trauma following normal saline infusion. methods: this study comprised 84 trauma patients with injury of mild severity in shahid rajaei hospital, shiraz, iran, during 2010-2011. the coagulation and metabolic values of each patient were measured before and one and six hours after infusion of one liter normal saline. then, the values of mentioned parameters on one and six hours after infusion were compared with baseline measures using repeated measures analysis of variance. results: eighty four patients included in the present study (76% male). hemoglobin (hb) (df: 2; f=32.7; p<0.001), hematocrit (hct) (df: 2; f=30.7; p<0.001), white blood cells (wbc) (df: 2; f=10.6; p<0.001), and platelet count (df: 2; f=4.5; p=0.01) showed the decreasing pattern following infusion of one liter of normal saline. coagulation markers were not affected during the time of study (p>0.05). the values of blood urea nitrogen (bun) showed statistically significant decreasing pattern (df: 2; f=5.6; p=0.007). pressure of carbon dioxide (pco2) (df: 2; f=6.4; p=0.002), bicarbonate (hco3) (df: 2; f=7.0; p=0.001), and base excess (be) (df: 2; f=3.3; p=0.04) values showed a significant deteriorating changes following hydration therapy. conclusion: it seems that, the infusion of one liter normal saline during one hour will cause a statistically significant decrease in hb, hct, wbc, platelet, bun, be, hco3, and pco2 in trauma patients with mild severity of injury and stable condition. the changes in, coagulation profiles, ph, pvo2, and electrolytes were not statistically remarkable. key words: fluid therapy; blood gas analysis; hemodilution; multiple trauma cite this article as: paydar s, bazrafkan h, golestani n, roozbeh j, akrami a, moradi am. effects of intravenous fluid therapy on clinical and biochemical parameters of trauma patients. emergency. 2014;2(2):90-5. introduction:1 rauma injury is one of the most important challenges confronting the field of medicine worldwide. annually, almost five millions people die from injuries (1). trauma, besides cancer and cardiac diseases are the leading causes of premature deaths in people before 65 years of age in many countries (2). uncontrolled bleeding, followed by hemorrhagic shock and coagulation abnormalities, is the main cause of preventable death in these patients (3, 4). fluid therapy is the cornerstone of treatment in such situation. the proper protocol of hydration therapy for trauma patients, has not yet been prepared. on the other hand, monitoring the hemodynamic and metabolic changes during resuscitation process is crucial (5-7). the effects *corresponding author: shahram paydar, md. trauma research center, shahid rajaei trauma hospital, shahid chamran blvd, shiraz, iran. tel/fax: +987116254206. email: paydarsh@sums.ac.ir received: 3 may 2014; accepted: 3 june 2014 of fluid therapy on hemodynamic and metabolic profile of the trauma patients are not completely clear. only, there are few studies in this field which all are almost based on elective surgery patients, self-experiences, and experts' opinions (8-11). it seems that, the increased intravascular volume could have various effects on clinical and para-clinical aspects of patients. the increasing circulating volume leads to mounting the cardiac output by a heightened preload. the subsequent elevated cardiac output causes some changes in patient`s clinical findings such as blood pressure, heart rate, urine output, and skin temperature (12). there are several laboratory markers which are representative of tissue perfusion and metabolic changes during resuscitation (13, 14). these indices include base excess, serum lactate, tissue ph, and blood urea nitrogen (bun) (14-16).the results of previous studies on effects of fluid therapy revealed various findings which could be due to the different situations, the severity of injury and t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 91 paydar et al initial hemodynamic and metabolic status of patients. to determine these effects, the present study was aimed to assess the changes in biochemical markers of trauma patients after infusion of one liter normal saline. methods: the present study was conducted in trauma center of shahid rajaei hospital, shiraz, iran, in 2010-2011. the study protocol was approved by ethics committee of shiraz university of medical sciences. written informed consent was obtained from all patients. the patients younger than 16 and older than 60 years old, pregnant women, diabetic patients, those receiving blood transfusion, patients suffered from hepatic or cardiac failure, and subjects with coagulation abnormalities were excluded from the study. the severity of injury in all included patients was mild (score=4) based on revised trauma score (rts). at the time of arrival to the emergency department, all the patients were visited and carefully examined by a general surgery resident. the metabolic and coagulation markers included complete blood count (cbc), bun, sodium (na), potassium (k), venous blood gas (vbg), international normalized ratio (inr), prothrombin time (pt), and partial thromboplastin time (ptt) were checked and entered to designed data form. clinical values such as heart rate, blood pressure and respiratory rate were also measured and calculated. then, one litter normal saline was infused to patients within one hour and the mentioned markers rechecked after one and six hours from admission time. all blood samples were derivate from the opposite site of punctured upper extremity. data were analyzed using the spss statistical software version 18.0. quantitative data were expressed as mean ± standard deviation and qualitative ones as frequency and percentage. repeated measures analysis of variances (anova) was used to compare the clinical and biochemical values of patients at one and six hours after fluid therapy with base line. p value < 0.05 was considered significant. results: of 84 patients who included in the present study, 64 (76%) were male. the mean age of patients was 32.1± 4.5 years. the types of injury were 54 (64.2%) long bones fracture, 9 (10.7%) head trauma, 4 (4.8%) chest trauma, and 17(20.2%) multiple trauma. the means of patients' systolic blood pressure, pulse rate, and respiratory rate on admission were 120.2±17.0 mmhg, 82.5±9.2/minute and 18.3±1.1/minute, respectively. table 1 compares vital signs of patients among the time of admission, one hour, and six hours after infusion. table 2 and figure 1 show the comparison of table 1: the comparison of vital signs on arrival time with those in one and six hours after infusion of one-liter normal saline (mean±sd)  vital signs admission 1 hour 6 hours p sbp (mmhg) 120.2±17.0 120.9±12.8 120.0±11.0 0.91 rr/minute 18.3±1.1 18.9±2.3 18.7±2.3 0.42 pr/minute 82.5±9.2 81.2±7.8 84.2±9.5 0.74 sbp: systolic blood pressure; rr: respiratory rate; pr: pulse rate. table 2: the comparison of coagulation and metabolic values (mean±sd) on arrival time with those in one and six hours after infusion of one-liter normal saline  characters admission 1 hour 6 hours p wbc/mm3 12869.5±5272.5 12739.1±5012.8 11104.7±3492.0 <0.001 hb (mg/dl) 13.7±1.6 13.05±1.8 12.7±1.8 <0.001 hct (%) 40.5±4.4 38.4±5.09 37.9±5.1 <0.001 plt/mm3 211160±64812 197443±57081 197987±60765 0.01 pt (second) 13.04±1.8 13.6±1.8 12.9±1.6 0.21 ptt (second) 39.4±5.5 39.7±6.9 40.8±8.1 0.26 inr 1.15±0.2 1.15±0.2 1.15±0.2 0.67 bun (mg/dl) 16.1±4.4 15.4±4.4 15.3±4.7 0.007 na (meq/l) 141.7±3.8 141.2±4.1 140.6±4.7 0.048 k (meq/l) 4.0±0.5 4.0±0.4 4.1±0.5 0.32 wbc: white blood cell; hb: hemoglobin; hct: hematocrit; plt: platelet: pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio; bun: blood urea nitrogen; na: sodium; k: potassium. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 90-95 92 coagulation and metabolic factors on arrival time with those in one and six hours after infusion of one-liter normal saline. hemoglobin (hb) (df: 2; f=32.7; p<0.001) and hematocrit (hct) (df: 2; f=30.7; p<0.001) levels both decreased one (phb<0.001; phct<0.001) and six (phb<0.001; phct<0.001) hours after infusion. platelet count decreased after one hour (p<0.01) and fixed in six hours (p<0.35) (df: 2; f=4.5; p=0.01). white blood cells (wbc) decreased during the both studied times (df: 2; f=10.6; p<0.001). coagulation markers were not affected during the time of study. the values of bun showed statistically significant decreasing pattern following hydration therapy (df: 2; f=5.6; p=0.007). table 3 and figure 2 shows the comparison of venous blood gas parameters on arrival time with those in one and six hours after infusion. pressure of carbon dioxide (pco2) (df: 2; f=6.4; p=0.002), bicarbonate (hco3) (df: 2; f=7.0; p=0.001), and base excess (be) (df: 2; f=3.3; p=0.04) values showed a significant deteriorating changes following infusion. discussion: according to the findings of present study, although different metabolic and coagulation markers showed various patterns of changes, there were statistically significant changes only in hb, hct, platelet, and bun values of patients following infusion of one liter normal saline. also among vbg parameters pco2, hco3, and be showed significant deteriorating pattern following hydration therapy. successful hydration therapy and fluid resuscitation is determined by maintenance of tissue perfusion. in this context, isotonic crystalloids usually are the first line fluid used in many trauma centers (17). on the other hand, crystalloids infusion leads to tissue edema, hemodilution and decreasing concentration of coagulative factors (18, 19). despite positive effects of fluid infusion on vital signs, the reduction possible in oxygen-carrying capacity and consequently deteriorating tissue perfusion are undeniable side effects. in other word, the vital signs were maintained in patients by temporary increase in intravascular volume according to frank starling law, at the cost of decreasing oxygen-carrying capacity. the study of lahsaee et al. showed significant a b c d figure 1: pattern of cell blood counts including hemoglobin (a), hematocrit (b), white blood cells (c), and platelet (d) changes following infusion of one liter normal saline at the time of study. ** significant difference from pre-treatment time at level p<0.001. * significant difference from baseline at level p<0.01. # significant difference from baseline at level p<0.05.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 93 paydar et al decrease in hb and hct values following the hydration therapy in elective surgery patients (20). crystalloid induced hemodilution may be exacerbated with lower hb in more severely-injured patients and unstable condition. because of the importance of fluid therapy in management of trauma patients, removing it to conduct researches about the impact of fluid therapy on different indices is not ethical (19). but some studies conducted on animals, reported the effect of fluid therapy on indices such as blood pressure, lactate level, and hct (19, 21). the effects of fluid therapy on be and lactate have been studied in several investigations with different results (12, 14). based on the finding of the present study, wbc count decreased one and six hour after table 3: the comparison of venous blood gas parameters (vbg) on arrival time with those in one and six hours after infusion of one liter normal saline (mean±sd)  parameters base line 1 hour 6 hours p pvo2 (mmhg) 42.6±26.45 45.5±19.1 45.3±19.8 0.38 pco2 (mmhg) 36.1±7.6 36.2±7.0 33.4±6.2 0.002 hco3 (mmol/l) 22.5±3.6 22.2±3.9 21.2±3.6 0.001 be (meq/l) -1.4±3.2 -1.9±3.6 -2.3±3.5 0.04 ph 7.41±0.07 7.40±0.05 7.42±0.05 0.08 vbg: venous blood gas; po2: venous pressure of oxygen; pco2: venous pressure of carbon dioxide; hco3: bicarbonate; be: base excess. a b c figure 2: pattern of venous blood gas parameters including bicarbonate (a), venous pressure of carbon dioxide (b), and base deficit (c) changes following infusion of one-liter normal saline at the time of study. ** significant difference from baseline at level p<0.001. * significant difference from baseline at level p<0.01. # significant difference from pre-treatment time at level p<0.05.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 90-95 94 normal saline infusion, which also may be due to hemodilution. the platelet count showed similar decreasing pattern to the wbc. coagulation profile did not experienced any significant changes. this issue was against the findings of chin lc et al., indicating the hypo-coagulation state as one of the important adverse effects of fluid therapy (22). there are few studies reporting sufficient amounts of vbg values in patients with injury of mild severity (23). in this study, the mean values of initial vbg were reported as near normal values in mild severity-injured trauma patients. acidosis is considered as one of the hydration side effects, in gerecht study (16, 24). but in the present study the ph level did not change significantly. this could be due the mild injury of the patients and low volume of fluid infusion. the finding of the present study revealed a worsening pattern of be, pco2, and hco3 following infusion of one liter normal saline. it seems that monitoring and assessment of the changes in these values are necessary in patients with more severe injuries. many studies have shown a reduction in bun level as a result of the increasing of urine output after normal saline infusion in trauma patients. as well, in this study the bun showed statistically significant decreasing changes after infusion of fluid. further studies including patients with more severe injury are required to evaluate the impact of fluid therapy on different clinical and para-clinical aspects of trauma patients. although more studies are needed in this area, it seems that we should revise our concept in trauma patients' resuscitation. however, it should be done noticing to patients` individual conditions, injury severity, vital signs, and primary laboratory findings such as hb, be, lactic acid and etc. conclusion: it seems that, the infusion of one liter normal saline during one hour will cause a statistically significant decrease in hb, hct, wbc, platelet, bun, be, hco3, and pco2 in trauma patients with mild severity of injury and stable condition. the changes in coagulation profiles, ph, pvo2, and electrolytes were not statistically remarkable. acknowledgments: the authors kindly appreciate the staffs of the trauma center of shahid rajaei hospital, shiraz, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. world health organization, violence prevention dept. the injury chart book: a graphical overview of the global burden of injuries. genova: 2002. 2. yoon pw, bastian b, anderson rn, collins jl, jaffe hw. potentially preventable deaths from the five leading causes of death united states, 2008-2010. morb mortal wkly rep. 2014;63(17):369-74. 3. miniño am, statistics ncfh. deaths: final data for 2004. department of health and human services, centers for disease control and prevention, national center for health statistics; 2007. 4. abbasi hr, mousavi sm, akerdi at, niakan mh, bolandparvaz s, paydar s. pattern of traumatic injuries and injury severity score in a major trauma center in shiraz, southern iran. bull emerg trauma. 2013;1(2):81-5. 5. brohi k, singh j, heron m, coats t. acute traumatic coagulopathy. j trauma acute care surg. 2003;54(6):1127-30. 6. macleod jb, lynn m, mckenney mg, cohn sm, murtha m. early coagulopathy predicts mortality in trauma. journal of trauma-injury, infection, and critical care. 2003;55(1):39-44. 7. holcomb jb. optimal use of blood products in severely injured trauma patients. hematology am soc hematol educ program. 2010;2010(1):465-9. 8. tien h, nascimento jr b, callum j, rizoli s. an approach to transfusion and hemorrhage in trauma: current perspectives on restrictive transfusion strategies. can j surg. 2007;50(3):202. 9. holcomb jb, wade ce, michalek je, et al. increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. ann surg. 2008;248(3):447-58. 10. holcomb jb, spinella pc. optimal use of blood in trauma patients. biologicals. 2010;38(1):72-7. 11. ho am-h, karmakar mk, dion pw. are we giving enough coagulation factors during major trauma resuscitation? am j surg. 2005;190(3):479-84. 12. maegele m, paffrath t, bouillon b. acute traumatic coagulopathy in severe injury: incidence, risk stratification, and treatment options. deutsches ärzteblatt international. 2011;108(49):827. 13. baratloo a, rahmati f, rouhipour a, et al. correlation of blood gas parameters with central venous pressure in patients with septic shock; a pilot study. bull emerg trauma. 2014;2(2):77-81. 14. kincaid eh, miller pr, meredith jw, rahman n, chang mc. elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization. j am coll surg. 1998;187(4):38492. 15. paladino l, sinert r, wallace d, anderson t, yadav k, zehtabchi s. the utility of base deficit and arterial lactate in differentiating major from minor injury in trauma patients with normal vital signs. resuscitation. 2008;77(3):363-8. 16. brunicardi f, brandt m, andersen d, et al. schwartz's principles of surgery absite and board review: mcgraw hill professional; 2010. 60 p. 17. moore km. controversies in fluid resuscitation. j trauma nurs. 2006;13(4):168-72. 18. waikar ss, chertow gm. crystalloids versus colloids for resuscitation in shock. curr opin nephrol hypertens. 2000;9(5):501-4. 19. lee c-c, chang i, yen z-s, et al. delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine response. ann emerg med. 2007;49(1):37-44. 20. lahsaee sm, ghaffaripour s, hejr h. the effect of routine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 95 paydar et al maintenance intravenous therapy on hemoglobin concentration and hematocrit during anesthesia in adults. bulletin of emergency and trauma. 2013;1(3 jul):102-7. 21. lu y-q, cai x-j, gu l-h, wang q, huang w-d, bao d-g. experimental study of controlled fluid resuscitation in the treatment of severe and uncontrolled hemorrhagic shock. journal of trauma-injury, infection, and critical care. 2007;63(4):798-804. 22. chien l-c, lu kj, wo cc, shoemaker wc. hemodynamic patterns preceding circulatory deterioration and death after trauma. j trauma. 2007;62(4):928-32. 23. rudkin se, kahn ca, oman ja, et al. prospective correlation of arterial vs venous blood gas measurements in trauma patients. the american journal of emergency medicine. 2012;30(8):1371-7. 24. gerecht r. the lethal triad. hypothermia, acidosis & coagulopathy create a deadly cycle for trauma patients. jems. 2014;39(4):56-60. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 122 emergency (2015); 3 (3): 122-124 casr report odontogenic pain as the principal presentation of vertebral artery pseudoaneurysm; a case report marco zenteno1, hernando raphael alvis-miranda2, angel lee1, luis rafael moscote-salazar2* 1. department of neurosurgery, national institute of neurology and neurosurgery, d.f. mexico, mexico. 2. department of neurosurgery, university of cartagena, cartagena de indias, colombia. *corresponding author r: luis rafael moscote-salazar. department of neurosurgery, university of cartagena, cartagena de indias, colombia. tel: +573012835380; e-mail: mineurocirujano@aol.com received: october 2014; accepted: january 2015 abstract dissection of the vertebral artery is an important but rare cause of cerebrovascular accidents. here we report a 48-year-old man with toothache since 4 days before who presented to the emergency department with neck pain and final diagnosis of dissecting right vertebral artery pseudoaneurysm. to our knowledge, this maybe the first report of odontogenic pain as the first manifestation of vertebral artery pseudoaneurysm in the literatures. key words: vertebral artery dissection, toothache, stroke. cite this article as: zenteno m, alvis-miranda hr, lee a, rafael l. odontogenic pain as the principal presentation of vertebral artery pseudoaneurysm; a case report. emergency. 2015; 3(3):122-24 introduction: issection of the vertebral artery is an important but a rare cause of cerebrovascular accidents (1). the annual incidence rate of vertebral artery dissection is estimated to be about 1-1.5 per 100,000 population. however it is responsible for 20% of cerebrovascular accidents in young adults and represents about 0.4 to 2.5% of all cerebrovascular events (2, 3). in recent years, this clinical entity has received more attention from neurologists and neurosurgeons, which has allowed its early and further diagnosis. learning various possible manifestations, can help lessen missed diagnosis. here we report a case of dissecting vertebral artery pseudoaneurysm, presenting itself with odontogenic pain principally. case report: a 48-year-old man suffering from toothache and neck pain was referred to the emergency department. toothache was initiated since four days ago. he was visited by dentists several times and taken different analgesics, without any improvement. the dental pain had exacerbated and neck pain was added, too. on arrival, he had normal vital signs and was conscious. he had stiff neck, but no focal neurologic deficits. other physical exams also did not reveal any positive finding. brain computed tomography (ct) scan revealed subarachnoid hemorrhage. three-dimensional ct angiography showed the presence of a dissecting pseudoaneurysm of the right vertebral artery (figures 1 and 2). we decided to eliminate it through endovascular approach, before a potentially lethal rupture. therefore, the patient underwent surgery with stent insertion. his post-operative evolution was completely satisfactory and he was discharged after 5 days. discussion: vertebral artery dissection is a recognized cause of ischemic stroke in young adults. atherosclerosis, connective tissue diseases, and cervical trauma are risk factors associated with development of this pathology (1, 3, 4). the pathophysiology of dissection and pseudoaneurysm basically consist of an initial intimal tear, followed by entry of blood between the intima and the adventitia, which leads to growing and ballooning of the pseudoaneurysm (5). vertebral and basilar arteries play the main role in the posterior circulation of brain. therefore, the most prevalent clinical symptoms of vertebral artery dissection consist of neck pain and posterior headache that may follow cerebrovascular accidents related to posterior circulation entity. if extra-cranial dissection extends to the intracranial fossa, and also in cases of primary intracranial dissection, subarachnoid hemorrhage may occur (6). some authors have declared that this should be considered as one of the differential diagnoses in patients referred with any cranio-cervical pain. but vertebral dissection presenting with facial pain has rarely been described in the literature (3, 7). modalities such as brain magnetic resonance imaging (mri), computed tomography, and conventional angiography are frequently used for diagnosis. in spite of all that, conventional digital subtraction angiography has d this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 123 emergency (2015); 3 (3): 122-124 figure 1: conventional angiography confirmed the pseudoaneurysm of the right vertebral artery. figure 1: three-dimensional computed angiography demonstrated the pseudoaneurysm of the right vertebral artery. remained as the gold standard in terms of diagnostic modality to make the proper diagnosis and have a dynamic evaluation of the blood flow through the visualized defect (8). a three-dimensional reconstruction shows important morphologic information of the lesion (9). dynamic computed tomography angiography (cta) can also provide critical hemodynamic information. standard ct and mri with or without contrast enable evaluation of surrounding neurovascular and soft tissue structures and provide a better understanding of the surrounding anatomy (10, 11). surgery could be accomplished by either endovascular technique or surgical trapping with clips above and below. some advantages of the endovascular management are as follows: it is minimally invasive, needs less time for vascular occlusion during repair, avoids devitalized tissue, and can be performed in the presence of previously instituted anti-platelet or anti-coagulant therapies (12-15). favorable outcome is assumed for younger patients, those who are diagnosed before appearing the stroke, and even in most ischemic strokes. on the other hand, late or missed diagnosis can lead to poor outcome (15-17). conclusion: dissection of the vertebral artery is a rare but important cause of cerebrovascular accidents in adults. becoming familiar with atypical manifestations, as in our case, can lead to early diagnosis and therefore may reduce morbidity and mortality. conflict of interest: none. funding support: none. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. mokri b, houser ow, sandok ba, piepgras dg. spontaneous dissections of the vertebral arteries. neurology. 1988;38(6):880-. 2. schievink wi, mokri b, o'fallon wm. recurrent spontaneous cervical-artery dissection. new england journal of medicine. 1994;330(6):393-7. 3. gottesman rf, sharma p, robinson ka, et al. clinical characteristics of symptomatic vertebral artery dissection. a systematic review. the neurologist. 2012;18(5):245. 4. kasmaei hd, baratloo a, nasiri z, soleymani m, yazdani mo. recombinant tissue plasminogen activator administration in patients with cerebrovascular accident; a case series. archives of neuroscience. 2015;2(2). 5. nader r, gragnaniello c. neurosurgery tricks of the trade: cranial: thieme; 2013. 6. baumgartner r, bogousslavsky j, caso v, paciaroni m. clinical manifestations of vertebral artery dissection. frontiers of neurology and neuroscience. 2005:77. 7. krespi y, gurol me, coban o, tuncay r, bahar s. vertebral artery dissection presenting with isolated neck pain. journal of neuroimaging. 2002;12(2):179-82. 8. chappell et, moure fc, good mc. comparison of computed tomographic angiography with digital subtraction angiography in the diagnosis of cerebral aneurysms: a metaanalysis. neurosurgery. 2003;52(3):624-31. 9. tanoue s, kiyosue h, kenai h, nakamura t, yamashita m, mori h. three-dimensional reconstructed images after rotational angiography in the evaluation of intracranial aneurysms: surgical correlation. neurosurgery. 2000;47(4):866-71. 10. nader r, gragnaniello c, berta sc, sabbagh aj, levy ml. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com zenteno et al 124 topic book review. 11. malhotra ak, camacho m, ivatury rr, et al. computed tomographic angiography for the diagnosis of blunt carotid/vertebral artery injury: a note of caution. annals of surgery. 2007;246(4):632-43. 12. brown m, rogers j, bland j. endovascular versus surgical treatment in patients with carotid stenosis in the carotid and vertebral artery transluminal angioplasty study (cavatas): a randomised trial. the lancet. 2001;357(9270):1729-37. 13. kitanaka c, tanaki j-i, kuwahara m, teraoka a, sasaki t, takakura k. nonsurgical treatment of unruptured intracranial vertebral artery dissection with serial follow-up angiography. journal of neurosurgery. 1994;80(4):667-74. 14. halbach vv, higashida rt, dowd cf, et al. endovascular treatment of vertebral artery dissections and pseudoaneurysms. journal of neurosurgery. 1993;79(2):18391. 15. khurana ds, bonnemann cg, dooling ec, ouellette em, buonanno f. vertebral artery dissection: issues in diagnosis and management. pediatric neurology. 1996;14(3):255-8. 16. de bray j, penisson-besnier i, dubas f, emile j. extracranial and intracranial vertebrobasilar dissections: diagnosis and prognosis. journal of neurology, neurosurgery & psychiatry. 1997;63(1):46-51. 17. shah q, messé sr. cervicocranial arterial dissection. current treatment options in neurology. 2007;9(1):55-62. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 64 emergency (2015); 3 (2): 64-69 original research oral midazolam-ketamine versus midazolam alone for procedural sedation of children undergoing computed tomography; a randomized clinical trial saeed majidinejad1, keramat taherian1*, mehrdad esmailian1, mehdi khazaei1, vajihe samaie2 1. department of emergency medicine, isfahan university of medical sciences, isfahan, iran. 2. department of internal medicine, isfahan university of medical sciences, isfahan, iran. *corresponding author: keramat taherian, emergency medicine resident, department of emergency medicine, al-zahra hospital, isfahan, iran. tel: +9809133072560; email: taranetaherian@yahoo.com received: september 2014; accepted: november 2014 abstract introduction: motion artifacts are a common problem in pediatric radiographic studies and are a common indication for pediatric procedural sedation. this study aimed to compare the combination of oral midazolam and ketamine (omk) with oral midazolam alone (om) as procedural sedatives among children undergoing computed tomography (ct) imaging. methods: the study population was comprised of six-month to six-year old patients with medium-risk minor head trauma, who were scheduled to undergo brain ct imaging. patients were randomly allocated to two groups: one group received 0.5 mg/kg midazolam (om group; n = 33) orally and the other one received 0.2 mg/kg midazolam and 5 mg/kg ketamine orally (omk group; n=33). the vital signs were monitored and recorded at regular intervals. the primary outcome measure was the success rate of each drug in achieving adequate sedation. secondary outcome measures were the time to achieve adequate sedation, time to discharge from radiology department, and the incidence of adverse events. results: adequate sedation was achieved in five patients (15.2%) in om group and 15 patients (45.5%) in omk group, which showed a statistically significant difference between the groups (p = 0.015). no significant difference was noted between om and omk groups with respect to the time of achieving adequate sedation (33.80 ± 7.56 and 32.87 ± 10.18 minutes, respectively; p = 0.854) and the time of discharging from radiology department (89.60 ± 30.22 and 105.27 ± 21.98 minutes, respectively; p=0.223). the complications were minor and similar among patients of both groups. conclusion: this study demonstrated that in comparison with om, omk was more effective in producing a satisfactory level of sedation in children undergoing ct examinations without additional complications; however, none of these two regimens fulfilled clinical needs for procedural sedation. key words: midazolam; ketamine; conscious sedation; tomography, x-ray computed cite this article as: majidinejad s, taherian k, khazaei k, samaie v. oral midazolam-ketamine versus midazolam alone for procedural sedation of children undergoing computed tomography; a randomized clinical trial. emergency. 2015;3(2):64-9. introduction: he results of imaging studies are negatively affected by patients’ movements; hence, patient’s cooperation is required during imaging. children’s movements and lack of cooperation are common indications for pediatric procedural sedation during imaging studies such as computed tomography (ct) scans (1). different rates of success have been achieved by various sedation regimens such as diphenhydramine, propofol, ketamine, midazolam (2), chloral hydrate (3), pentobarbital (4), and dexmedetomidine (5); therefore, the efforts to find an ideal regimen are continued. the selected sedative should have a rapid onset of action, few adverse effects, short and sufficient duration of action, self-maintenance of a patent airway, minimal effects on respiration or hemodynamics, and rapid recovery (6). over the last few years, researchers have shown a special interest in finding effective, nonparenteral, sedative agents that do not have injection problems (3). ketamine is a noncompetitive antagonist of the n-methyl-d-aspartate receptor (nmdar), which is used for premedication, sedation, and induction as well as maintenance of general anesthesia. quick onset, short duration of action, and maintenance of laryngeal reflexes have made it a popular sedative choice for pediatric patients in the emergency department (7). although ketamine is known as a parenteral agent, some researchers have successfully used it as an oral sedative drug (8, 9). midazolam is t this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 65 emergency (2015); 3 (2): 64-69 a potent benzodiazepine with rapid onset and offset effects as well as anxiolytic and amnestic properties, which can be administered through different routes (i.e. oral, intravenous, intramuscular, rectal, sublingual, and intranasal). oral midazolam (om) is a safe and effective choice for sedation in children (10). in previous studies, the authors have used a combination of oral midazolam and ketamine (omk) as premedication and sedative regimens; besides, some studies reported that combination therapy has higher efficacy without any additional adverse effects in comparison to the methods using each drug alone (11, 12). to the best of our knowledge, limited number of studies have reported the use of om during imaging, which had reported lower effectiveness rate in comparison with chloral hydrate (13, 14); however, omk has not been used for this purpose, yet. therefore, this study was conducted to compare the effects of omk with om as procedural sedatives in pediatric patients undergoing ct imaging. methods: study design and setting this randomized, double-blinded, clinical trial was conducted from november 2012 to november 2013 in two teaching hospitals (ayatollah kashani hospital and alzahara hospital) affiliated to isfahan university of medical sciences, isfahan, iran. the study protocol was approved by ethics committee of the isfahan university of medical sciences. all parents or guardians were informed of the study's protocol, risks, and benefits and were asked to sign an informed written consent. participants we included six-month to six-year old children with medium-risk minor head trauma who were scheduled to undergo brain ct scan (15). medium-risk minor head trauma was defined as initial glasgow coma scale score of 15 with any history of brief loss of consciousness, posttraumatic amnesia, vomiting, headache, or intoxication. all of these patients were classified as status i or ii according to american society of anesthesiologists (asa) physical status classification. children with neurological disorders, anomalies of the cardiovascular system, known allergy to midazolam, gastritis, any serious systemic diseases, those on long-term treatment with hepatic enzyme-inducing drugs or those receiving erythromycin concurrently (due to drug interaction), and patients who had received medication within the preceding 48 hours were excluded. procedure patients were randomly allocated to two groups; om group received 0.5 mg/kg midazolam (produced by; tehran shimi, tehran, iran) orally and omk group received 0.2 mg/kg midazolam and 5 mg/kg ketamine (produced by; rotexmedica, trittau, germany) orally. randomization was conducted using a computer-generated sequence and block randomization protocol. demographic and basic characteristics such as age, height, gender, weight, body mass index (bmi), and history of any medical condition were recorded before administration of study drugs. then a nurse, who was blinded to the study, mixed both of the medications with 5 ml of sugar syrup to make it palatable. the parents gave the prepared syrup to the children under the researchers’ supervision. pulse rate and oxygen saturation (sao2) were continuously monitored by a portable pulse oximeter. blood pressure, heart rate, respiratory rate, and sao2 were recorded at baseline (just before drug administration) and every 30 minutes until the patient was discharged from the radiology department. the level of sedation of patients after drug administration was assessed using ramsay sedation scale (rss) (16). rss of four was considered as adequate sedation depth to tolerate diagnostic imaging studies. patients who did not show satisfactory response to the sedative drugs within 40 minutes and those who were awakened or moved during the imaging were excluded from further analysis. the interval between administration of sedative drugs and achieving rss of four was considered as the time to achieve adequate sedation. once the patients achieved adequate sedation, they were transferred to a scanner room and the imaging was performed according to the protocol. after the scan, the patients were transferred to another room in the radiology department to monitor and observe their conditions. the time to discharge from radiology department was defined as the interval between the start of sedative administration and return to the baseline alertness and spontaneous breathing. statistical analyses all statistical analyses were performed using the spss 19.0 (spss inc., chicago, il, usa). the categorical data were analyzed using fisher's exact test. parametric data were analyzed using the student’s t-test. descriptive statistics were expressed as mean ± standard deviation or number (percentage). statistical significance was set at p < 0.05. two-way anova was used to compare changes of vital signs during 180 minutes after drug administration between two groups. results: 66 participants were enrolled. figure 1 shows the consort flow diagram of study. the mean age of participants was 2.8 ± 1.6 years (range: 6 months to 6 years) and 54.5% of the participants were male. table 1 shows the basic characteristics of patients. there was no significant difference between the two groups in age, height, weight, and male to female ratio (table 1). table 2 compares outcomes between two groups. adequate sedation (rss of 4) was achieved in five patients (15.2%) in the om group and 15 patients (45.5%) in the omk group, which showed a statistically significant difference (p = 0.015). no significant difference was found between the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidinejad et al 66 groups in time of achieving adequate sedation (p = 0.854) and the time of discharging from radiology department (p = 0.223). adverse effects observed in two patients (one with nausea and another with vomiting) in the om group and three patients (two with nausea and one patient with vomiting) in the omk group. complications were minor and transient and did not differ between study groups (p > 0.05). no serious adverse events were seen in the study participant. systolic blood pressure, sao2 level, pulse rate, and respiratory rate figure 1: consort flow diagram of study table 1: demographic characteristics of the participants a characteristics midazolam midazolam-ketamine p value height (centimeter) 101 ± 19 103 ± 20 0.147 weight (kilogram) 15.7 ± 4.8 17.5 ± 14.6 0.234 age (year) 3.0 ± 1.6 2.6 ± 1.6 0.369 male to female ratio 17:16 19:14 0.805 a, data are presented as mean ± standard deviation. table 2: the outcomes of patients in midazolam and midazolam-ketamine groups outcome om group omk group p value adequately sedated1 5 (15.2%) 15 (45.5%) 0.015 time2 to become adequately sedated 33.80 ± 7.56 32.87 ± 10.18 0.854 time2 to discharge from rd 89.60 ± 30.22 105.27 ± 21.98 0.223 om: oral midazolam; omk: combination of oral midazolam-ketamine; rd: radiology department. 1, number (%); 2, mean ± standard deviation (minute) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 67 emergency (2015); 3 (2): 64-69 showed no significant inter-group differences at baseline and at various time points after administration of the drugs (for all analysis: df = 18, p > 0.05, figure 2). discussion: our investigation showed that in comparison to om, omk successfully induced sedation in 45% of the patients. om failed to sedate the patient in 85% of the cases and led to administration of additional medication and longer time to obtain the scan. ketamine is used for premedication, sedation, and induction as well as maintenance of general anesthesia with minimal effect on respiration and tendency to preserve autonomic reflexes (7). oral ketamine (ok) has been used for pediatric sedation in previous studies. it has been reported that 10 mg/kg of ketamine provides effective sedation and analgesia in young children undergoing wound repair processes (9). moreover, 6 mg/kg of ok was reported to be effective in sedation for outpatient pediatric dental surgeries (10). om is the most commonly used premedication in the united states (18), which has been used as a safe and effective sedative in pediatrics, mainly in pediatric dentistry (10, 17); however, intravenous midazolam has been found to induce more sedation (18). intravenous or nasal midazolam has gained widespread popularity as a sedative for children undergoing radiographic studies such as ct scan (19 figure: inter-group differences of vital signs at baseline and at various time points after administration of midazolam and combination of midazolam-ketamine (df: 18, p > 0.05 for all comparisons). 80 90 100 110 120 130 140 150 h e a r t r a te (b e a t/ m in u te ) time (minute) midazolam midazolam/ketamine 20 25 30 35 40 45 r e s p ir a to r y r a te (p e r m in u te ) time (minute) midazolam midazolam/ketamine 80 85 90 95 100 105 110 115 120 s y s to li c b lo o d p r e s u r e (m m h g ) time (minute) midazolam midazolam/ketamine 90 91 92 93 94 95 96 97 98 99 100 s a o 2 (% ) time (minute) midazolam midazolam/ketamine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidinejad et al 68 21). the omk and om alone are safe, effective, and practical approach to manage children for minor dental procedures (22, 23). the efficacy of om and ketamine, alone or in combination has been studied in pediatric dentistry sedation and premedication (24-26). younge et al. reported better sedative effects during suturing lacerations with ok (10 mg/kg) in comparison to om (0.7 mg/kg) (27). although our study was consistent with the previous studies regarding the higher efficacy of omk in comparison to om, most of the previous studies reported success rates of 60% to 90% for om (11, 17, 28) and 46% to 95% for omk (11, 22). barkan et al. showed that the combination of oral midazolam (0.5 mg/kg) and ketamine (5 mg/kg) led to deeper sedation in comparison with om (0.5 mg/kg) alone in children requiring laceration repair. in addition, 27% of patients in the om group and 6% in the omk group needed further intravenous sedation (11). moriera et al. (12) compared the efficacy of om (1 mg/kg) and the omk (midazolam, 0.5 mg/kg; and ketamine, 3 mg/kg) for guiding the behavior of children undergoing dental treatment and reported higher efficacy of omk. on the other hand, there are several studies reporting lower success rate, which are similar to our findings. moro-sutherland et al. (6) compared the sedative effects of intravenous midazolam with pentobarbital during brain ct imaging in children aged six months to six years. they administered pentobarbital to 29 patients (53%) and midazolam (mean dose, 0.2 ± 0.03 mg/kg) to 26 patients (47%). in the midazolam group, only five patients (19%) were successfully scanned with midazolam alone and the remaining 21 patients (81%) required additional medication and took a longer time to scan. another investigation reported a failure rate of 60% in administrating intranasal midazolam (0.2 mg/kg) for sedation of children undergoing ct scan (3). molter et al. (29) used 0.4 mg/kg of om 20 minutes before the induction of general anesthesia and reported a mild or no sedative effect in 76% to 84% of patients. in this study, the onset time of adequate sedation was 33 minutes in om group and 32 minutes in omk group. younge et al. (27) reported an onset time of 20 minutes for ok and 43 minutes for om. other studies reported that the time to reach optimal sedation level would be 15 minutes for om (10, 17). studies, which used om (0.5-1 mg/kg) as premedication reported that the best time for optimal preoperative sedation would be 30 to 45 minutes before scan (30). this time for ketamine is 25 to 45 minutes (9, 31). barkan observed that the needed time to achieve adequate sedation was 17 minutes for om and 14 minutes for omk. the patients' blood pressure, respiratory rate, pulse rate, and sao2 levels did not show any significant changes during the sedation. although ketamine and midazolam affect the respiratory and hemodynamics responses (11), our results were in line with the findings of previous studies that reported minimal effects of low-dose om and ok on these parameters (17, 31). although further studies are needed to confirm or refute our results and attention to the pharmacological aspects is necessary, lower efficacy of om in this study could be explained as follows: first, we used these drugs for ct imaging that needs a deeper level of sedation in comparison with some other studies that used those drugs in other settings as premedication. second, in the previous studies, intravenous forms of these drugs were used, which might bring about unexpected results; the same drugs in different studies should be compared with caution. third, the ethnic differences in response to these sedative agents might affect the results. variability of drug response is an important consideration in clinical medicine. a major cause of variations in drug responses is hepatic cytochrome p450 oxidase (cyp450)-mediated drug metabolism (29). distribution volumes and metabolism determine the pharmacokinetics of midazolam. midazolam is almost exclusively metabolized by cyp450 3a (cyp3a) isoenzymes (32). there are several limitations to this study. first, we could not purchase the oral form of drugs. although previous studies have shown that these parenteral forms can be used orally, the oral form of drugs might bring about results that are more precise. second, the number of participants who were included in the final analysis (as sedated patients) was small. conclusion: this study demonstrated that in comparison with om, omk was more effective in producing a satisfactory level of sedation in children undergoing ct examinations without additional complications; however, none of these two regimens fulfilled clinical needs for procedural sedation. acknowledgments: the authors appreciate the insightful cooperation of staff of the emergency department. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. cravero jp, blike gt, beach m, et al. incidence and nature of adverse events during pediatric sedation/anesthesia 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puentes p, carrasco p, villena r. oral ketamine and midazolam for pediatric burn patients: a prospective, randomized, double-blind study. j pediatr surg. 2013;48(3):629-34. 27. younge pa, kendall jm. sedation for children requiring wound repair: a randomised controlled double blind comparison of oral midazolam and oral ketamine. emerg med j. 2001;18(1):30-3. 28. silver t, wilson c, webb m. evaluation of two dosages of oral midazolam as a conscious sedation for physically and neurologically compromised pediatric dental patients. pediatr dent. 1994;16:350-. 29. mcgraw j, waller d. cytochrome p450 variations in different ethnic populations. expert opin drug metab toxicol. 2012;8(3):371-82. 30. weldon bc, watcha mf, white pf. oral midazolam in children: effect of time and adjunctive therapy. anesth analg. 1992;75(1):51-5. 31. bui t, redden rj, murphy s. a comparison study between ketamine and ketamine-promethazine combination for oral sedation in pediatric dental patients. anesth prog. 2002;49(1):14-8. 32. wandel c, böcker r, böhrer h, browne a, rügheimer e, martin e. midazolam is metabolized by at least three different cytochrome p450 enzymes. br j anaesth. 1994;73(5):658-61. archives of academic emergency medicine. 2019; 7 (1): e44 or i g i n a l re s e a rc h one-month follow-up of patients with unspecified abdominal pain referring to the emergency department; a cohort study seyed mohammad hoseininejad1, reza jahed2, mohammad sazgar3, fatemeh jahanian3, seyed jaber mousavi4, seyed hosein montazer3, touraj assadi3, hamed aminiahidashti3∗ 1. gut and liver research center, mazandaran university of medical sciences, sari, iran. 2. student research committee, mazandaran university of medical sciences, sari, iran. 3. emergency department, mazandaran university of medical sciences, sari, iran. 4. department of community medicine, mazandaran university of medical sciences, sari, iran. received: june 2019; accepted: july 2019; published online: 17 august 2019 abstract: introduction: about one third of patients referring to emergency department (ed) with abdominal pain, are discharged without a definite diagnosis. this study aimed to investigate the one-month outcome of patients with unspecified abdominal pain. methods: this cohort study was conducted on subjects who were evaluated in ed with unspecified abdominal pain and were referred to the gastroenterology clinic and followed for one month. finally, they were divided into two groups of cases with clear cause of abdominal pain and unclear cause of abdominal pain and patients’ characteristics were compared between the groups. results: 150 cases with the mean age of 40.68 ± 18.34 years were studied (53.3% female). after one month, 67 (44.7%) patients still complained of abdominal pain. a definitive cause of abdominal pain was established in 88 (58.7%) cases. there was not any significant difference between groups regarding, sex distribution (p = 012), duration of pain (p = 0.11), history of previous similar pain (p = 0.136), pain radiation (p = 0.737), length of hospital stay (p = 0.51), and presence of anorexia (p = 0.09), nausea and vomiting (p= 0.50), fever (p = 1.0), diarrhea (p = 0.23), and constipation (p = 0.07). there was a significant difference between the groups regarding location of pain (p = 0.017), age (p = 0.001) and history of comorbid diseases (p = 0.046). the predictive factors of finding a clear cause for abdominal pain in one-month follow-up, were leukocytosis (or: 5.92 (95% ci: 2.62 – 13.39); p < 0.001), age (or: 2.78 (95% ci: 1.15 – 6.71); p = 0.023), and outpatient follow-up (or: 1.04 (95% ci: 1.02 – 1.07); p < 0.001). conclusion: approximately, 40% of patients who were discharged with unspecified abdominal pain did not receive a clear diagnosis after one month of follow-up. older age, leucocytosis in initial evaluations, and outpatient follow-up increased the probability of finding a clear cause for abdominal pain in the mentioned cases. keywords: abdominal pain; patient discharge; follow-up studies; emergency service, hospital cite this article as: hoseininejad s m, jahed r, sazgar m, jahanian f, mousavi s j, montazer s h, assadi t, aminiahidashti h. one-month follow-up of patients with unspecified abdominal pain referring to the emergency department; a cohort study. arch acad emerg med. 2019; 7(1): e44. 1. introduction acute abdominal pain is defined as a non-traumatic pain that has begun less than 5 days before (1). it is one of the ∗corresponding author: hamed aminiahidashti; imam khomeini hospital, amirmazandarani boulevard, sari, iran. email: hamedaminiahidashti@yahoo.com tel: +98 9113540546 most common clinical complaints of patients that refer to the emergency department (ed) and is the cause of about 7-10% of all ed referrals (2, 3). despite the high frequency of these referrals to the ed, there is no definitive diagnostic way to distinguish between emergency and non-emergency causes for abdominal pain (1). 28% to 36% of these patients are discharged without definite diagnosis (4-6). the unclear cause of abdominal pain in the ed is commonly associated with insufficient history taking, inadequate use of diagnosthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s m. hoseininejad et al. 2 tic tests, and problems related to follow-up visit and test results (7). this challenge in differential diagnosis of abdominal pain can result in adverse consequences and legal and medical lawsuits (8). although thorough physical examination, careful observation, and repeated diagnostic tests are effective ways to reduce the risk of harmful and unintended consequences (9), in many cases, patients are dissatisfied with the long waiting time in ed (10). in addition, there is no specific guideline for dealing with patients with abdominal pain without definite diagnosis in ed (11). based on above-mentioned points, this study aimed to investigate the one-month outcome of patients with abdominal pain without definite diagnosis in ed. 2. methods 2.1. study design and setting this cohort study was conducted in gastroenterology research center, imam khomeini hospital, mazandaran university of medical sciences, sari, iran from march 2016 to february 2017. imam khomeini educational hospital is a public and tertiary referral center in mazandaran province with 400 beds, and the gastroenterology center is one of the first research centers in this area. this study was conducted on subjects who were admitted to the ed with abdominal pain with icd 10 code r10.4. all patients with abdominal pain (icd10 code r10) were visited by an emergency medicine specialist and they were admitted to the observation unit of ed for at least 6 hours and the serious causes of abdominal pain were ruled out. patients with abdominal pain who were diagnosed at this stage were excluded. patients with unclear diagnosis were referred to the gastroenterology clinic and followed for one month. finally, patients were divided into two groups of patients with clear cause of abdominal pain and unclear cause of abdominal pain after one-month follow-up and patients’ characteristics were compared between groups. all information of the participants was confidential and they were enrolled into the study after obtaining the consent of the patient or their relatives. this study was approved by the ethics committee of mazandaran university of medical sciences with the reference code: ir.mazums.rec.95-1625. 2.2. participants all patients with non-traumatic abdominal pain who were discharged without a definite diagnosis despite physical examination, laboratory, and imaging studies (icd 10 code r10.4) were included in the study. addicts or those with a history of addiction, pregnant women, patients with abdominal pain following trauma, those who left the ed against medical advice, and those who were lost to follow-up after a month, were excluded. in addition, patients who were under observation for 6 hours and a definite cause was diagnosed and those whose clinical condition was not suitable for discharge and were admitted to ward according to the decision of the emergency medicine specialist were excluded. 2.3. patients’ follow-up a summary of the patient’s ed clinical profile was given to each patient and referred to the gastroenterology clinic. every week the patients’ data were collected from the gastroenterology clinic and they were contacted via phone after a month. in addition, a visit was arranged with the patient or their relatives, and the completed investigation, definitive diagnosis, recovery, mortality and morbidity were questioned and recorded. 2.4. data gathering definitive diagnosis, age, sex, duration of pain, severity and location of pain, duration of admission, underlying disease, accompanying signs and symptoms, laboratory findings, as well as the results of one-month follow-up regarding readmission, pain status, cause of pain, and mortality were collected using a predesigned checklist. data from each of the groups were collected by the main author without any intervention in the patient’s treatment and care process. 2.5. statistical analysis all data were collected and recorded in spss statistical software version 22.0. quantitative data were described as mean ± standard deviation. frequency and percentage of variables were used to describe qualitative data. chi square (x2) test and logistic regression analysis were used to determine the associated factors of the probability to reach a definite diagnosis. p value less than 0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of studied patients 39,817 patients were admitted to the emergency department during the study period (4162 cases was classified as icd10 code r10). only 328 (7.77%) patients were eligible for enrollment to the study (icd10 code r10.4) and, finally, a study was conducted on 150 patients (figure 1). the subjects’ mean age was 40.68 ± 18.34 (6-85) years (53.3% female). in a re-visit to gastroenterology clinic after one month, 83 (55.3%) patients noted their pain was relieved, and 67 (44.7%) patients still complained of their pain. meanwhile, 63 (42%) patients complained of multiple referrals due to abdominal pain. a definitive cause of abdominal pain was established in 88 (58.7%) cases, yet the cause of abdominal pain was still unclear in 62 (41.3%) patients. most patients were diagnosed with renal colic (16.6%), followed by biliary colic (8.7%) and ovarian this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e44 figure 1: patient selection flowchart. cyst (5.3%). 3.2. comparing the groups table 1 and figure 2 compare the baseline characteristics of patients with clear and unclear causes of abdominal pain. there was not any significant difference between patients with clear and unclear cause of abdominal pain regarding, sex distribution (p = 012), duration of pain ( p = 0.11), history of previous similar pain (p = 0.136), pain radiation (p = 0.737), length of hospital stay (p = 0.51), and presence of anorexia ( p = 0.09), nausea and vomiting (p= 0.50), fever (p = 1.0), diarrhea (p = 0.23), and constipation (p = 0.07). patients with clear cause of abdominal pain were older than those with unclear cause (p = 0.001). there was a significant difference between groups regarding the location of pain at the time of presenting to ed (p = 0.017) and history of comorbid disease (p = 0.046). although the frequency of leukocytosis (wbc > 11,000) was not significantly different between the two groups, mean wbc count on the first day of admission was significantly higher in patients with clear cause (10.5 ± 3.40 versus 9.4 ± 3.17 × 103/µl; p = 0.043). table 2 compares the one-month outcomes of cases with clear and unclear cause of abdominal pain. based on logistic regression analysis, the predictive factors of finding a clear cause for abdominal pain in one-month follow-up were leukocytosis (or: 5.92 (95% ci: 2.62 – 13.39); p < 0.001), age (or: 2.78 (95% ci: 1.15 – 6.71); p = 0.023), and outpatient follow-up (or: 1.04 (95% ci: 1.02 – 1.07); p < 0.001). 4. discussion in this study, it was found that approximately 40% of patients who were discharged with abdominal pain without a definite diagnosis did not receive a final definitive diagnosis or clear cause. the most common definite diagnosis in this study was kidney stones. older age, leucocytosis in initial evaluations, and outpatient follow-up increased the probability of finding a clear cause for abdominal pain in the mentioned patients. in some studies, appendicitis (12) and gastric ulcers (13) were reported as the most common causes of abdominal pain without definite diagnosis. in our study, the pain associated with renal stones (renal colic) was the most common cause of abdominal pain, which was similar to the findings of cervellin et al. (6). it was previously shown that older age is associated with increased hospitalization length and definitive diagnosis (14), which is consistent with the results of our study. in addition, increased likelihood of problems such as mesenteric ischemia, and rupture of aortic aneurysm in cases with underlying diseases such as diabetes and hypertension, makes further workups necessary in these groups of subjects (15, 16). although in some studies there was no significant relationship between leukocyte count and definitive diagnosis of abdominal pain (13), in our study the increase in white blood cells had a significant relationship with finding a definitive cause for abdominal pain. in the study of cervellin, 6.9% of patients with abdominal pain returned to the emergency department within the first 5 days, and 7.6% of the patients returned within 5 days to one month after discharge. in the second visit, the initial diagnosis was changed to renal colic in many of these patients (6). in the present study 150 patients were discharged, 87 of whom were readmitted to emergency department and 67(44.67%) had definite diagnosis in readmission. in a study, it was shown that pain in the right lower quadrant of the abdomen is likely associated with definitive diagnosis and led to surgery, especially in older people (17). patients with abdominal pain who are discharged without a definite diagnosis are recommended to refer to a medical center if abdominal pain continues for 2 consecutive days (18). in our study, abdominal pain patients discharged without a definite diagnosis who were re-visited in the gastroenterology clinic were more likely to receive a definite diagnosis. this demonstrates the importance of follow-up. if there is suspicion of patients’ inability to follow up, they should remain in the ed under observation and the emergency department should provide the needed facilities. patients with abdominal pain discharged without a definite diagnosis should be carefully evaluated. patients with older age, readmission, and leukocytosis may be at risk for presence of a clear cause for abdominal pain. so they may benefit from longer observation and consultation for hospitalizathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s m. hoseininejad et al. 4 figure 2: location of pain in cases with clear and unclear cause of abdominal pain (p = 0.017). rlq: right lower quadrant of abdomen, llq: left lower quadrant of abdomen, ruq: right upper quadrant of abdomen, luq: left upper quadrant of abdomen. table 1: comparing the baseline characteristics of patients with clear and unclear cause of abdominal pain variable cause of abdominal pain p value clear (n = 88) unclear (n = 62) age (years) mean ± sd 44.9 (18.7) 34.5 (15.9) 0.001 gender male 45 (51.1) 25 (40.3) 0.12 female 43(48.9) 37(59.7) duration of pain before admission (hours) mean ± sd 35.1(47.5) 58.7(128.1) 0.11 history of similar pain yes 17 (70.8) 7 (29.2) 0.136 no 71 (56.3) 55 (43.7) length of hospital stay (days) mean ± sd 6.7 (4.4) 6.1 (5.1) 0.51 history of comorbidity1 yes 48 (54.5) 23 (37.1) 0.046 no 40 (50.6) 39 (49.4) pain radiation yes 6 (66.7) 3 (33.3) 0.737 no 82 (58.2) 59 (41.8) presenting sign and symptom anorexia 13 (14.8) 16 (25.8) 0.09 nausea and vomiting 51(58.0) 32 (51.6) 0.50 fever 7 (8.0) 5 (8.1) 1.0 diarrhea 5 (5.7) 7 (11.3) 0.23 constipation 5 (5.7) 9 (14.5) 0.08 laboratory findings leukocytosis2 33 (40.7) 15 (25.9) 0.07 anemia3 32 (39.5) 25 (43.1) 0.32 data are presented as mean ± standard deviation (sd) or number (%). 1: diabetes mellitus, hypertension, renal stone, menorrhagia, ovarian cyst, discopathy, gi bleeding, end stage renal disease, and etc., 2: white blood cell count ≥11×103 /µl, 3: hemoglobin<10 mg/dl. tion. in case of discharge, patients with abdominal pain who are discharged without a definite diagnosis should be monitored by family physicians and/or as an outpatient referring again after a specific interval with specific instructions at the time of discharge. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e44 table 2: comparing the one-month outcomes of cases with clear and unclear cause of abdominal pain variables cause of abdominal pain p value clear (n = 88) unclear (n = 62) pain condition painless 55 (62.5) 48 (77.4) 0.07 painful 33 (37.5) 14 (22.6) readmission yes 27 (35.5) 40 (64.5) <0.001 no 61 (69.3) 22 (35.5) mortality yes 7 (8.0) 2 (3.2) 0.308 no 81 (42.6) 60 (57.4) data are presented as number (%). 5. limitation there were several limitations in this study. many of the patients who enrolled did not fully cooperate or provided incorrect information on their diagnostic and therapeutic procedures. patients’ medical records were incomplete in some cases, which caused a limitation in the number of samples. 6. conclusion approximately 40% of patients who were discharged with abdominal pain without definite cause did not receive a clear diagnosis. older age, leucocytosis in initial evaluations, and outpatient follow-up increased the probability of finding a clear cause for abdominal pain in the mentioned patients. 7. appendix 7.1. acknowledgements this research is based on the thesis of dr. reza jahed, who graduated from mazandaran university of medical sciences. we sincerely thank staff of the emergency department, gastroenterology clinic and medical records department of imam khomeini hospital, sari, mazandaran province, iran. 7.2. author contribution all authors met the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids seyed mohammad hoseininejad: 0000-0002-1713-5791 mohammad sazgar: 0000-0001-7497-3364 fatemeh jahanian: 0000-0002-5961-6315 seyed jaber mousavi: 0000-0002-9623-2708 seyed hosein montazer: 0000-0002-9785-586x touraj assadi: 0000-0003-2336-6470 hamed aminiahidashti: 0000-0002-2115-1903 7.3. funding/support none. 7.4. conflict of interest there are no conflicts of interest. references 1. gans sl, pols ma, stoker j, boermeester ma, expert steering g. guideline for the diagnostic pathway in patients with acute abdominal pain. digestive surgery. 2015;32(1):23-31. 2. hastings rs, powers rd. abdominal pain in the ed: a 35 year retrospective. the american journal of emergency medicine. 2011;29(7):711-6. 3. niska r, bhuiya f, xu j. national hospital ambulatory medical care survey: 2007 emergency department summary. national health statistics reports. 2010(26):1-31. 4. cooper jg, hammond-jones d, o’neill e, patel r, murphy r, clamp se, et al. the clinical decision unit has a role to play in the management of acute undifferentiated abdominal pain. european journal of emergency medicine : official journal of the european society for emergency medicine. 2012;19(5):323-8. 5. caporale n, morselli-labate am, nardi e, cogliandro r, cavazza m, stanghellini v. acute abdominal pain in the emergency department of a university hospital in italy. united european gastroenterology journal. 2016;4(2):297-304. 6. cervellin g, mora r, ticinesi a, meschi t, comelli i, catena f, et al. epidemiology and outcomes of acute abdominal pain in a large urban emergency department: retrospective analysis of 5,340 cases. annals of translational medicine. 2016;4(19):362. 7. medford-davis l, park e, shlamovitz g, suliburk j, meyer an, singh h. diagnostic errors related to acute abdominal pain in the emergency department. emergency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s m. hoseininejad et al. 6 medicine journal : emj. 2016;33(4):253-9. 8. kachalia 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biomedicine. 2016;6(2):10. 13. coskun a, yavasoglu i, sargin g, ok im, bircan m, avcil m, et al. the role of mean platelet volume in patients with non-specific abdominal pain in an emergency department. przeglad gastroenterologiczny. 2015;10(3):156-9. 14. pappas a, toutouni h, gourgiotis s, seretis c, koukoutsis i, chrysikos i, et al. comparative approach to non-traumatic acute abdominal pain between elderly and non-elderly in the emergency department: a study in rural greece. journal of clinical medicine research. 2013;5(4):300-4. 15. espinoza r, balbontin p, feuerhake s, pinera c. [acute abdomen in the elderly]. revista medica de chile. 2004;132(12):1505-12. 16. esses d, birnbaum a, bijur p, shah s, gleyzer a, gallagher ej. ability of ct to alter decision making in elderly patients with acute abdominal pain. the american journal of emergency medicine. 2004;22(4):270-2. 17. marco ca, schoenfeld cn, keyl pm, menkes ed, doehring mc. abdominal pain in geriatric emergency patients: variables associated with adverse outcomes. academic emergency medicine : official journal of the society for academic emergency medicine. 1998;5(12):1163-8. 18. forouzanfar mm, hatamabadi hr, hashemi b, majidi a, baratloo a, shahrami a, et al. outcome of nonspecific abdominal pain in the discharged patients from the emergency department. journal of gorgan university of medical sciences. 2014;16(2):62-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e14 or i g i n a l re s e a rc h arterial blood gas analysis of patients with tramadolinduced seizure; a cross sectional study bita dadpour1, anahita alizadeh1, maryam vahabzadeh1, seyed reza mousavi1, mohammad moshiri1, zahra ataee1, babak mostafazadeh2,3∗ 1. medical toxicology research center, mashhad university of medical sciences, mashhad, iran. 2. toxicological research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of forensic medicine and toxicology, shahid beheshti university of medical sciences, tehran, iran. received: january 2020; accepted: january 2020; published online: 1 march 2020 abstract: introduction: tramadol is an active analgesic drug that is commonly used to treat moderate to severe pain. the present study aimed to assess the arterial blood gas (abg) analysis of patients with tramadol-induced seizure (tis). methods: this prospective cross-sectional study was performed on 50 tis cases that were referred to emergency department within a maximum of one hour after their last episode of seizure. the results of abg analysis on admission were collected and their association with dosage and time interval between ingestion and admission was assessed. results: 50 cases with the mean age of 35.10 ± 9.62 years were studied (80.0% male). the mean dosage of ingestion was 1122.00 ± 613.88 (400 to 3000) mg and the mean time interval between ingestion and admission was 7.16 ± 2.18 hours. abg analysis on admission showed that 49 (98.0%) patients had ph < 7.35 and paco2 > 45 mmhg (respiratory acidosis). there was a significant association between ingestion to admission time interval and both paco2 (r = -0.330, p = 0.019), and pao2 (r = 0.303, p = 0.032). the dose of ingestion was negatively associated with respiratory rate (r = -0.556, p = 0.001), arterial ph (r = -0.676, p = 0.001), and pao2 (r = -0.514, p = 0.001), but was positively associated with paco2 (r = 0.461, p = 0.001). higher doses of tramadol led to more severe hypercapnia and need for intubation (or = 1.12, 95% ci: 0.88 – 1.26; p = 0.045). 5 (10.0%) cases needed mechanical ventilation. all patients improved after supportive care with no in-hospital death. conclusion: based on the findings, 98% of tis cases had respiratory acidosis. higher doses of ingested drug and longer time interval between ingestion and admission were associated with severity of abg disturbances. keywords: tramadol; blood gas analysis; seizures; acidosis, respiratory; hypercapnia cite this article as: dadpour b, alizadeh a, vahabzadeh m, mousavi s r, moshiri m, ataee z, mostafazadeh b. arterial blood gas analysis of patients with tramadol-induced seizure; a cross sectional study. arch acad emerg med. 2020; 8(1): e14. 1. introduction tramadol is an active analgesic drug, which is commonly used to treat moderate to severe pain with different sources. according to the literature, this analgesic agent is one of the most prescribed opioids worldwide (1, 2). the mechanism of action of the drug is stimulation of µ-opioid receptor as well as inhibition of serotonin and noradrenaline reuptake (3). however, the analgesic effect of the drug is mainly dependent on its non-opioid properties and through activation of central monoaminergic pathways (4). due to its high efficacy, ∗corresponding author: babak mostafazadeh, loghman hakim hospital, tehran, iran. e-mail: mstzbmd@sbmu.ac.ir, tel: 00982151025376 especially in pain relief, the misuse of tramadol has been reported in almost all clinical settings in the world; leading to potential complications such as seizure, which has been reported in 15% to 35% of patients (5, 6). the exact mechanisms of tramadol-induced seizure (tis) remains unexplained; however, it seems that its inhibitory effects on gamma-aminobutyric acid (gaba) receptors along with its opioid receptor agonist activity play pivotal roles (7). tis may appear by consuming recommended doses (8). moreover, the risk of seizure occurring may also synergistically increase by simultaneous use of other drugs such as phenothiazines, tricyclic antidepressants, and selective serotonin reuptake inhibitors (9, 10). there are two important points about tis. first, the minimum stimulant dose of drug that causes seizures and also this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. dadpour et al. 2 its blood concentrations remain unknown. in addition, there are some evidence for effects of tramadol on arterial blood gas (abg) disturbances, especially rise in carbon dioxide pressure (pco2), which leads to respiratory depression (11). in this regard, we hypothesize that occurrence of seizure following tramadol use may be related to increased blood pco2. the present study aimed to assess arterial blood gas (abg) analysis of patients with tramadol-induced seizure (tis). 2. methods 2.1. study design and setting this prospective cross-sectional study was performed on 50 cases that were referred to emergency department of payambaran hospital, tehran, iran, within a maximum of one hour after tis (patients with a history of tramadol ingestion followed by generalized tonic-clonic seizure), from july to december 2019. the results of abg analysis on admission were collected and their association with dosage and time interval between ingestion and admission was assessed. the protocol of study was approved by ethics committee of shahid beheshti university of medical sciences, tehran, iran (ethics code: ir.sbmu.retech.rec.1398.355). 2.2. participants patients with a history of tramadol use with subsequent generalized seizure (diagnosed as tramadol-induced seizure) that were referred to emergency department of our hospital within a maximum of one hour after last episode of seizure were included in this study. patients with history of head trauma, multi drug ingestion, positive amphetamine test, history of methamphetamine, morphine, or methadone abuse, the use of psychological medications such as tricyclic antidepressants, phenothiazine, or selective serotonin reuptake inhibitors, presenting to the hospital more than one hour after the last seizure episode, or any other reason for the seizure, were excluded. 2.3. data gathering on admission, the patients’ baseline characteristics (gender, age, time and dose of taking medication, history of seizures before hospitalization), the level of consciousness (according to the richmond agitation-sedation scale), vital signs (blood pressure, respiratory rate, pulse rate, temperature), need for mechanical ventilation, and at the time of discharge, duration of hospital stay were collected using a predesigned checklist. also, the results of abg analysis were collected on admission and then 12 hours after the initial assessment. an expert toxicologist was responsible for data gathering. table 1: baseline characteristics of the study population variable value gender male 41 (82.0) female 9 (18.0) age (year) mean ± sd 35.10 ± 9.62 time between tramadol use and admission (hours) < 3 9(18.0) 3 6 24(48.0) ≥ 6 17(34.0) dose of drug used (mg) < 500 8(16.0) 500 1000 29(58.0) ≥ 1000 13(26.0) medical history chronic use of tramadol 30 (60.0) previous seizure 9 (18.0) epilepsy 1 (2.0) pre-hospital seizure frequency one time 36 (72.0) two times 13 (26.0) three times 1 (2.0) in-hospital seizure yes 9 (18.0) no 41 (82.0) need for intubation yes 5 (10.0) no 45 (90.0) level of consciousness (rass score) -1 2 (4.0) -2 33 (66.0) -3 14 (28.0) -4 1 (2.0) data are presented as mean ± standard deviation or frequency (%). rass: richmond agitation-sedation scale. 2.4. statistical analysis the results were presented as mean ± standard deviation (sd) for quantitative variables and were summarized by absolute frequencies and percentages for categorical variables. normality of data was analyzed using the kolmogorovsmirnoff test. categorical variables were compared using chi-square test or fisher’s exact test. quantitative variables were also compared using t test, or mann-whitney u test. the association between the quantitative variables was tested via pearson’s correlation test. to assess the relationship of time and dose of tramadol used with the change in abg parameters with the presence of other variables as the confounders, the multivariable regression model was employed. for the statistical analysis, the statistical software spss version 16.0 for windows (spss inc., chicago, il) was used. p values of 0.05 or less were considered statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e14 table 2: vital signs and blood gas analysis changes during the 12-hour monitoring parameter on admission after 12 hours p value blood pressure 108.21 ± 20.14 111.90 ± 10.72 0.159 heart rate 104.46 ± 9.09 94.43 ± 7.38 < 0.001 respiratory rate 9.88 ± 1.45 12.61 ± 0.81 < 0.001 body temperature 37.11 ± 0.26 36.98 ± 0.12 < 0.001 ph 7.28 ± 0.03 7.33 ± 0.02 < 0.001 hco3 level 17.58 ± 1.29 20.06 ± 1.20 < 0.001 pco2 53.80 ± 5.94 46.76 ± 2.56 < 0.001 pao2 88.24 ± 2.98 95.68 ± 1.20 < 0.001 data are presented as mean ± standard deviation. 3. results 3.1. baseline characteristics of studied cases 50 tramadol-induced seizure cases with the mean age of 35.10 ± 9.62 (range: 25-45) years were studied (80.0% male). the mean dosage of tramadol used was 1122.00 ± 613.88 (400 to 3000) mg that led to one, two and three episodes of pre-hospital seizures in 72.0%, 26.0%, and 2.0% of patients, respectively. the patients’ characteristics on admission are summarized in table 1. the mean time interval between use and admission was 7.16 ± 2.18 hours. 3.2. blood gas analysis arterial blood gas analysis on admission showed that 49 (98.0%) patients had ph < 7.35 and pco2 > 45 mmhg (respiratory acidosis). there was a significant association between tramadol use to seizure time interval and blood pressure (r = 0.308, p = 0.030), heart rate (r = -0.441, p = 0.001), body temperature (r = -0.281, p = 0.048), pco2 (r = -0.330, p = 0.019), and po2 (r = 0.303, p = 0.032). the dose of medication used was negatively associated with blood pressure (r = -0.351, p = 0.030), respiratory rate (r = -0.556, p = 0.001), arterial ph (r = -0.676, p = 0.001), and pao2 (r = -0.514, p = 0.001), but was positively associated with pco2 (r = 0.461, p = 0.001). higher doses of tramadol led to more severe hypercapnia and need for tracheal intubation (or = 1.12, 95% ci: 0.88 – 1.26; p = 0.045). 3.3. outcomes in most patients, the blood gas indices had significantly improved within 12 hours via supportive approaches (table 2). 5 (10.0%) cases needed mechanical ventilation. all patients improved after supportive care with no in-hospital death. the mean length of hospital stay was 2.04 ± 0.92 days (ranged 1 to 5 days). higher dose of tramadol used was closely associated with longer hospital stay (beta = 0.683, p = 0.001). 4. discussion based on the findings of the present study, higher doses of tramadol were associated with worse in-hospital outcome and led to more severe acid-base disturbances, which manifested as respiratory acidosis and hypercapnea. on the other hand, higher doses of tramadol use before admission can predict severe in-hospital complication and therefore, more severe blood gas disturbances in affected patients. review of the literature indicated the risk for generalized seizure in up to 41% of tramadol users. however, the studies had also revealed that the likelihood of tramadol-induced seizure depends on various factors such as the definition and classification of seizures or simultaneous use of other analgesics such as codeine (12). furthermore, these studies demonstrate an increased risk of seizure only at the highest level of tramadol exposure. however, some other studies showed the risk of seizure with even moderate doses of drug. in other words, the association between time and dose of tramadol consumption and the risk of seizure occurrence remains uncertain. as clearly determined in the present study, first, higher doses of tramadol was associated with worse in-hospital outcome such as more respiratory depression, more need for tracheal intubation and also longer hospital stay. in other words, consuming higher doses of tramadol led to more severe acidbase disturbances manifested as respiratory acidosis and hypercapnea that might lead to worse outcome. thus, higher paco2 may be predictable in patients receiving high prehospital tramadol dosages. respiratory effects of tramadol have been previously described along with other potential side effects, especially acid-base disturbances. in a study by tantry et al. in 2011, a patient scheduled for thigh reductionplasty was candidate for pain relief using tramadol with a moderate dose (200mg), which led to severe respiratory acidosis leading to emergency intubation and mechanical ventilation. in another experiment by ismail et al. (13), about one-third of patients who had received tramadol with a 1600 mg dose suffered from respiratory acidosis with considerably raised pco2. also, as clearly shown by rahimi et al. (14), the mean ingested dose of 1971.2 mg (range: 100-20000 mg) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. dadpour et al. 4 tramadol led to occurrence of seizure in 47.91% and pure acute respiratory acidosis in almost all tramadol-intoxicated patients. also, similar to our study, they indicated significant differences between cases with seizure and cases without seizure according to time interval between tramadol ingestion and hospital admission as well as ingested dose of drug. therefore, summing our findings and the results of previous studies shows that in patients suffering from tis, higher doses of tramadol and also longer time interval between tramadol ingestion and hospital admission may result in more severe acid-base disturbances such as respiratory acidosis. the association between the occurrence of seizure and the change in acid-base balance in tis has not been previously examined. 5. limitation respiratory changes with hypercapnia and hypoxemia, which can occur with seizures, have been exclusively studied in previous experiments. however, in our study and due to the lack of designing a case-control study with both seizure and non-seizure subgroups, assessing the relationship between the likelihood of seizure and respiratory acidosis following the use of high dose of tramadol was impossible, which should be considered as a major target in future studies. 6. conclusion based on the findings, 98% of tis cases had respiratory acidosis. higher doses of ingested drug and also longer time interval between ingestion and admission were associated with higher severity of abg disturbances. 7. declarations 7.1. acknowledgements the article is financially supported by toxicological research center, shahid beheshti university of medical sciences, tehran, iran. the authors express their appreciation to clinical toxicology department, payambaran hospital, tehran, iran. 7.2. author contribution all authors devised the work, the main conceptual ideas, proof outline and interpretation of the data. also, all authors discussed the cases and commented on the manuscript. all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids bita dadpour: 0000-0001-6004-0344 anahita alizadeh: 0000-0001-8441-1197 maryam vahabzadeh: 0000-0002-6234-1834 seyed reza mousavi: 0000-0002-3817-5928 mohammad moshiri: 0000-0003-0389-2270 zahra ataee: 0000-0002-4636-9263 babak mostafazadeh: 0000-0003-4872-9610 7.3. funding/support the article is financially supported by toxicological research center, shahid beheshti university of medical sciences, tehran, iran. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present work. references 1. sweileh wm, shraim ny, zyoud sh, al-jabi sw. worldwide research productivity on tramadol: a bibliometric analysis. springerplus. 2016;5(1):1108. 2. subedi m, bajaj s, kumar ms, yc m. an overview of tramadol and its usage in pain management and future perspective. biomedicine & pharmacotherapy = biomedecine & pharmacotherapie. 2019;111:443-51. 3. frink mc, hennies h, englberger w, haurand m, wilffert b. influence of tramadol on neurotransmitter systems of the rat brain. arzneimittel-forschung. 1996;46(11):102936. 4. desmeules ja, piguet v, collart l, dayer p. contribution of monoaminergic modulation to the analgesic effect of tramadol. british journal of clinical pharmacology. 1996;41(1):7-12. 5. shadnia s, soltaninejad k, heydari k, sasanian g, abdollahi m. tramadol intoxication: a review of 114 cases. human & experimental toxicology. 2008;27(3):201-5. 6. taghaddosinejad f, mehrpour o, afshari r, seghatoleslami a, abdollahi m, dart rc. factors related to seizure in tramadol poisoning and its blood concentration. journal of medical toxicology. 2011;7(3):183. 7. rehni ak, singh i, kumar m. tramadol-induced seizurogenic effect: a possible role of opioid-dependent yaminobutyric acid inhibitory pathway. basic & clinical pharmacology & toxicology. 2008;103(3):262-6. 8. boostani r, derakhshan s. tramadol induced seizure: a 3-year study. caspian journal of internal medicine. 2012;3(3):484. 9. kroenke k, krebs e, bair m. general hospital psychiatry. gen hosp psychiatry. 2009;31(3):206-19. 10. sansone ra, sansone la. tramadol: seizures, serotonin syndrome, and coadministered antidepressants. psychiatry (edgmont). 2009;6(4):17. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e14 11. mattia c, mazzaferro s, coluzzi f, luzi m. respiratory depression following iatrogenic tramadol overuse in a patient with chronic renal failure. the journal of headache and pain. 2004;5(2):137. 12. morrow rl, dormuth cr, paterson m, mamdani mm, gomes t, juurlink dn. tramadol and the risk of seizure: nested case-control study of us patients with employersponsored health benefits. bmj open. 2019;9(3):e026705. 13. ismail ma, mahmoud sf, khedr ma, mohammed mk. assessment of cases of acute tramadol toxicity as regards clinical, laboratory and management procedures in some university hospitals in cairo. egyptian journal of hospital medicine. 2018;72(1). 14. rahimi hr, soltaninejad k, shadnia s. acute tramadol poisoning and its clinical and laboratory findings. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2014;19(9):855. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2018; 6 (1): e17 ca s e re p o rt loss of guide wire as an important complication of central venous catheterization; a case report fares najari1∗, mohamadjavad amirian1, sara sadjadi1, ideh baradaran kayal2 1. department of forensic medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. legal medicine organization, alborz university of medical sciences, karaj, iran. received: january 2018; accepted: february 2018; published online: 5 march 2018 abstract: many critically ill patients need aggressive procedures, such as central venous catheterization. the complication rate of central venous line placement is estimated to be 15%. common complications include arterial puncture, hematoma, pneumothorax, hemothorax, arrhythmia, thoracic duct injury, infection, and thrombosis. cardiac tamponade, pericardial effusions, pleural effusions, air or guidewire embolisms, and lost guide wires are rare but severe complications. here we report a case of lost guide wire following central venous line insertion. keywords: catheterization, central venous; intraoperative complications; emergency service, hospital; case report; rare diseases © copyright (2018) shahid beheshti university of medical sciences cite this article as: najari f, amirian m, sadjadi s, baradaran kayal i. loss of guide wire as an important complication of central venous catheterization; a case report. emergency. 2018; 6 (1): e17. 1. introduction many critically ill patients need aggressive procedures for treatment; one of these procedures is central venous catheterization. the complication rate of these procedure is estimated to be 15% (1). common complications are arterial puncture, hematoma, pneumothorax, hemothorax, arrhythmia, thoracic duct injury, infection, and thrombosis (2, 3). cardiac tamponade, pericardial effusions, pleural effusions, air or guidewire embolism, and lost guide wire are rare but severe complications. there are some case reports of lost guide wires, such as the cases reported by kumar et al. in 2006 (4), satoshi akazawa et al. in 1996 (5), khatami et al. in 2010 (6), muhammad qamarul hoda et al. (7), and mohammad kashif et al. (8). here we report a case of lost guide wire following central venous line insertion. ∗corresponding author: fares najari; department of forensic medicine, shohadaye tajrish hospital, shahrdari street, tajrish square, tehran, iran. postal code: 1981964771 tel: 00989123195140 email: fares.hospital@yahoo.com 2. case presentation: patient was a 32-year-old pregnant woman (g3p2) who became a surrogate mother on november 18th, 2015. the embryo was implanted successfully and she was carrying twins without any complications. in the 33r d week of pregnancy ( june 23r d , 2016), she had blood spotting and premature rupture of membranes and underwent caesarean section in a general hospital. her first laboratory test results were as follows: hemoglobin 10.7 mg/dl; hematocrit 31.4%; white blood cell 10.7 1000/mm3 (neutrophil count 80%). the twins were born with apgar score 7/10. the patient had severe bleeding due to uterine adhesion to the bladder (placenta percreta) and the surgeon decided to block the ovarian arteries. two days after surgery, an infectious diseases specialist consultation was requested because of the patient’s high fever and tachycardia. laboratory tests indicated the following: white blood cell 14 1000/mm3 (neutrophil 93%); esr 120; crp 94.5. due to inappropriate peripheral intravenous line, placement of a central venous catheter via the right femoral vein was attempted by the anesthesiologist. twelve days after caesarian section, the patient had no fever and she left the hospital with personal consent and against medical advice. sixteen days later, the patient was hospitalized in another hospital due to pain and edema of her right leg. she underwent doppler sonography of the right lower extremity and warfarin therapy for suspect deep vein this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. najari et al. 2 figure 1: anterior-posterior and lateral view of right knee, anterior-posterior view of pelvis, and magnetic resonance imaging of patient’s right knee. thrombosis (dvt). she was discharged from the hospital with oral warfarin after 15 days of hospitalization. four days after discharge, she returned to the same hospital with pain and hematoma above the right knee. doppler sonography revealed chronic dvt and a multiple septate region without echo. radiography and magnetic resonance imaging of the right knee revealed the lost guide wire in her right femoral vein (figure 1). the guide wire was retrieved on the next day. patient sued the anesthesiologist and the medical commission of medical procedures declared medical negligence because of commission. 3. discussion the most frequent reported late complications for central vein catheterizations are thrombosis and infection (9, 10). there are also some rare complications that have been reported, such as migration of the guide wire to the pulmonary artery, entrapment of the fractured guide wire, knotting of the guide wire during catheter insertion, and formation of a femoral arteriovenous fistula. a rarely reported complication of central venous line catheterization is missing guide wire, which can result in arrhythmias, in–travascular entrapment of wires, embolization of wire frag–ments, and vessel perforation. gou h et al. reported a 40-year-old male patient who underwent central venous catheterization via the left subclavian vein, but staff did not notice that a guide wire was completely inserted in the vein. after six months, the lost guide wire was seen extending from the saphenous vein through the vena cava, right atrium, right ventricle, pulmonary artery, and lung tissue to the back of the neck (11). schummer w et al. also reported four cases of loss of guide wire after central venous catheterization (12). there are various reasons for loss of guide wire including forgetfulness of the physician performing the procedure and a part of the wire being fractured. obviously, the physician and the assistant nurse should be careful regarding used devices and parts not being lost just like other procedures. on the other hand, if we notice that a part of guide wire has remained in the vein due to any reason including fracture, we should better attempt to retrieve the remaining part by consulting vascular surgeons. it seems that use of ultrasound before and after placement this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e17 of central line and use of a checklist during procedure, may help identify and prevent similar complications. 4. appendix 4.1. acknowledgements we would like to express our special thanks to the forensic center of tehran, iran. 4.2. author’s contribution all authors meet the four criteria of authorship contribution based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declared no potential conflict of interest with respect to authorship and/or publication of this article. 4.4. funding and support none. references 1. mcgee dc, gould mk. preventing complications of central venous catheterization. new england journal of medicine. 2003;348(12):1123-33. 2. comerlato ph, rebelatto tf, de almeida s, augusto f, klein lb, boniatti mm, et al. complications of central venous catheter insertion in a teaching hospital. revista da associacao medica brasileira. 2017;63(7):613-20. 3. askegard-giesmann jr, caniano da, kenney bd, editors. rare but serious complications of central line insertion. seminars in pediatric surgery; 2009: elsevier. 4. kumar s, eapen s, vaid v, bhagwat a. lost guide wire during central venous cannulation and its surgical retrieval. indian journal of surgery. 2006;68(1):33. 5. akazawa s, nakaigawa y, hotta k, shimizu r, kashiwagi h, takahashi k. unrecognized migration of an entire guidewire on insertion of a central venous catheter into the cardiovascular system. anesthesiology: the journal of the american society of anesthesiologists. 1996;84(1):241-2. 6. khatami mr, abbasi r, sadigh g. guide wire migration during femoral vein catheterization. iranian journal of kidney diseases. 2010;4(4):333-5. 7. hoda mq, das g, mamsa ka, salimullah h. unusual site of guide-wire entrapment during central venous catheterization. jpma the journal of the pakistan medical association. 2006;56(3):139-41. 8. kashif m, hashmi h, jadhav p, khaja m. a missing guide wire after placement of peripherally inserted central venous catheter. the american journal of case reports. 2016;17:925. 9. durbec o, viviand x, potie f, vialet r, albanese j, martin c. a prospective evaluation of the use of femoral venous catheters in critically ill adults. critical care medicine. 1997;25(12):1986-9. 10. joynt gm, kew j, gomersall cd, leung vy, liu ek. deep venous thrombosis caused by femoral venous catheters in critically ill adult patients. chest. 2000;117(1):178-83. 11. guo h, peng f, ueda t. loss of the guide wire: a case report. circulation journal: official journal of the japanese circulation society. 2006;70(11):1520-2. 12. schummer w, schummer c, gaser e, bartunek r. loss of the guide wire: mishap or blunder? british journal of anaesthesia. 2002;88(1):144-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references archives of academic emergency medicine. 2020; 8(1): e46 ca s e re p o rt covid-19 pneumonia in asymptomatic trauma patients; report of 8 cases majid samsami1, javad zebarjadi bagherpour1∗, behzad nematihonar1, hamed tahmasbi1 1. department of general surgery, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 6 april 2020 abstract: we are currently involved in the novel coronavirus 2019 (covid-19) pandemic. a considerable number of covid-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers. in this study, we reported 8 incidentally detected cases of covid-19 pneumonia in chest computed tomography (ct) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms. keywords: covid-19, pneumonia, injuries cite this article as: samsami m, zebarjadi bagherpour j, nematihonar b, tahmasbi h. covid-19 pneumonia in asymptomatic trauma patients; report of 8 cases. arch acad emerg med. 2020; 8(1): e46. 1. introduction the global incidence of novel coronavirus 2019 (covid-19) that involves the lower respiratory tract (pneumonia) continues to rise since december 2019 (1). the specific source and the exact primary mode of transmission of 2019-ncov to humans remain unknown. the clinical features and laboratory and radiological abnormalities of covid-19 infections are not specific and are similar to other respiratory tract infections (2). it is now evident that most cases of covid-19 disease develop mild respiratory and constitutional symptoms such as fever, cough, dyspnea, myalgia, and fatigue (3). a considerable number of covid-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers (4). in the study performed by khazaee et al. (5), several patients had incidental evidence of covid-19 infection on chest ct scans obtained for trauma management. in another study, hu et al. (6), described clinical features of 24 asymptomatic patients on their study, five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. twelve (50.0%) cases showed typical ct scan images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. the remaining 7 (29.2%) cases had a normal ct image and had no ∗corresponding author: javad zebarjadi bagherpour; department of general surgery, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989182101497, email: javad.zebarjady@yahoo.com, symptoms during hospitalization and none of the 24 cases developed severe covid-19 pneumonia. in this study, we report 8 incidentally detected cases of covid-19 pneumonia in chest computed tomography (ct) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms. this cases series study was performed on multiple trauma patients who were referred to emergency department of imam hossein hospital, tehran, iran, from 17 to 28 march 2020. patients who underwent chest ct scan for trauma management and had radiographic manifestations of covid-19 pneumonia on ct scan were enrolled. demographic information (age, gender), mechanism of trauma, as well as chest ct scan and rt-pcr for covid-19 results were collected and reported for enrolled cases. 2. case presentation 8 patients with the mean age of 49.71 ± 13.13 (range: 34 – 67) years were studied (62.5% male). the trauma mechanism was fall from height in 5 (62.5%) and car accident in 3 (37.5%) cases. none of the patients had symptoms in favor of covid-19 infection such as fever, dyspnea, headache, cough, etc. at the time of admission. 5 (62.5%) patient had history of close contact with a suspected covid-19 case. physical examinations of lungs revealed no signs of pneumonia. a chest ct scan without contrast was performed to evaluate high-energy trauma and the findings strongly were in favor of pneumonia. the results of rt-pcr was positive for covid19 infection in all patients. during the hospital stay, two patients (25%) experienced mild symptoms such as fever, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. samsami et al. 2 figure 1: axial chest computed tomography (ct) scan without contrast of asymptomatic covid-19 patients obtained during evaluation for multiple trauma. cough, and myalgia and the rest stayed asymptomatic. in the laboratory results, 4 (50%) patients had a slight increase in c reactive protein (maximum 18) and the rest of the laboratory findings were normal. two patients underwent orthopedic surgery without any respiratory complication. all patients received standard treatment (hydroxychloroquine with or without azithromycin). none of the patients required intensive care. all patients were discharged from hospital after completion of treatment and had no mortality. figure 1 shows axial cuts of the cases’ chest ct scan. 3. discussion the widespread distribution of covid-19 is a major concern, globally. understanding of the transmission risk is incomplete. epidemiologic investigation in wuhan at the beginning of the outbreak identified an initial association with a seafood market that sold live animals, where most patients had worked or visited, which was subsequently closed for disinfection (7). with droplet transmission, virus is shed via the respiratory secretions when a person with infection coughs, sneezes, or talks, which can infect another person if it makes direct contact with their mucous membranes. infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth. droplets typically do not travel more than six feet (about two meters) and do not linger in the air (8). the interval during which an individual with covid-19 is infectious is uncertain and the maximum incubation period for covid-19 is thought to be 14 days following exposure, with most cases occurring approximately four to five days after exposure. during the incubation period, the patient can pass on the disease to others (9). in the study performed by khazaee et al. (5), several patients had incidental evidence of covid-19 infection on chest ct scan for trauma management. in the present study, all patients had evidence suggesting covid-19 in ct scan, which was confirmed by rt-pcr after hospital admission. in this study, only 2 patients experienced mild symptoms and none of the patients developed severe symptoms. none of the patients in hu et al. (6), study had severe illness and no death occurred. they observed a typical asymptomatic transmission to family members living in the same household, which even caused severe covid-19 pneumonia. overall, the asymptomatic carriers identified from close contacts were prone to becoming mildly ill during hospitalization. physicians and therapists working in trauma centers should treat patients with extreme caution and personal protection. also, during this pandemic, measures must be taken in trauma emergency departments to prevent transmission of the disease. 4. conclusion according to the findings of this study, asymptomatic trauma patients can be carriers of the disease and cause transmission. it is important for physicians and staff at trauma centers to know how to use personal protective equipment to prevent catching the disease. 5. declarations 5.1. acknowledgements the authors would like to thank the patients and the supporting staff in this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e46 5.2. conflict of interest none. 5.3. funding there is no funding and support. references 1. guan w-j, ni z-y, hu y, liang w-h, ou c-q, he j-x, et al. clinical characteristics of coronavirus disease 2019 in china. new england journal of medicine. 2020. 2. organization wh. surveillance case definitions for human infection with novel coronavirus ( ncov ): interim guidance v1, january 2020. world health organization, 2020. 3. wu z, mcgoogan jm. characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72âăŕ314 cases from the chinese center for disease control and prevention. jama. 2020. 4. yang y, lu q, liu m, wang y, zhang a, jalali n, et al. epidemiological and clinical features of the 2019 novel coronavirus outbreak in china. medrxiv. 2020. 5. khazaei m, asgari r, zarei e, moharramzad y, haghighatkhah h, taheri ms. incidentally diagnosed covid19 infection in trauma patients; a clinical experience. archives of academic emergency medicine. 2020;8(1):31. 6. hu z, song c, xu c, jin g, chen y, xu x, et al. clinical characteristics of 24 asymptomatic infections with covid-19 screened among close contacts in nanjing, china. science china life sciences. 2020:1-6. 7. world health organization. january 22. . novel coronavirus situation report -2. (accessed on january. 2020) 8. van doremalen n, bushmaker t, morris dh, holbrook mg, gamble a, williamson bn, et al. aerosol and surface stability of sars-cov-2 as compared with sars-cov-1. new england journal of medicine. 2020. 9. chan jf-w, yuan s, kok k-h, to kk-w, chu h, yang j, et al. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet. 2020;395(10223):514-23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2018; 6 (1): e1 or i g i n a l re s e a rc h predictive factors of mortality in acute amphetamine type stimulants poisoning; a review of 226 cases mitra rahimi1, somaieh lookzadeh1, roxana sadeghi2, kambiz soltaninejad3, shahin shadnia1∗, abdolkarim pajoumand1, hossein hassanian-moghaddam1, nasim zamani1, masoud latifi-pour1 1. toxicology research center, excellence center of clinical toxicology, department of clinical toxicology, loghman hakim hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. cardiology department, loghman hakim hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of forensic toxicology, legal medicine research center, legal medicine organization, tehran, iran. received: august 2017; accepted: october 2017; published online: 10 january 2018 abstract: introduction: amphetamine type stimulants (ats) such as amphetamine and methamphetamine (ma) are one of the most important causes of poisoning in the world. in this study we aimed to define the predictive factors of mortality in acute ats poisoning patients. methods: this is a retrospective cross-sectional study on all cases with acute ats poisoning who were referred to a referral center for poisoning, tehran, iran, from april 2011 to march 2014. using patients’ medical records, demographic data, route of exposure, type and amount of ats, the cause of poisoning, clinical presentations, and electrocardiogram (ecg) and laboratory findings, as well as patient’s outcomes were collected and analyzed regarding the independent predictive factors of mortality. results: 226 cases with the mean age of 32.9 ± 10.9 years were studied (77% male). ma was the most abused ats (97.4%) and the most frequent route of exposure was oral (55.3%). the mortality rate was 5.4%. there was a significant association between agitation (p = 0.002), seizure (p = 0.001), loss of consciousness (p < 0.001), creatine phosphokinase level (p = 0.002), serum ph (p = 0.002), serum hco3 (p = 0.02), and pco2 (p = 0.01) with mortality. however, serum hco3 [or=1.27 (95% ci: 1.07-1.50); p value=0.005], pco2 [or=0.89 (95% ci: 0.84-0.96); p value=0.002], and loss of consciousness [or=0.019 (95% ci: 0.003-0.106); p value=0.000] were the only independent predictive factors of mortality. conclusion: pco2 ≥ 51 mmhg, serum bicarbonate ≤ 22.6 meq/l, and loss of consciousness on admission could be considered as prognostic factors of mortality in acute ats poisoning cases presenting to emergency department. keywords: amphetamines; patient outcome; prognostic factors; poisoning; substance abuse © copyright (2018) shahid beheshti university of medical sciences cite this article as: rahimi m, lookzadeh s, sadeghi r, soltaninejad k, shadnia sh, a pajoumand, hassanian-moghaddam h, zamani n, latifi-pour m. predictive factors of mortality in acute amphetamine type stimulants poisoning; a review of 226 cases. emergency. 2018; 6(1): e1. 1. introduction a mphetamine type stimulants (ats) refer to a class of substances whose main derivatives are amphetamine and methamphetamine (ma). also, a range of other substances such as ephedrine, pseudoephedrine, methylphenidate, methcathinone, and 3,4methylenedioxymethamphetamine (mdma) are included in this group ∗corresponding author: shahin shadnia; department of clinical toxicology, loghman hakim hospital poison center, kamali street, south karegar avenue, tehran, iran. tel/fax: +98-21-55424041, cell phone: +98-912-1947601 email: shahin1380@yahoo.com (1, 2). the production and abuse of ats have increased worldwide. however, the pattern of abuse of each type of ats is different throughout the world based on social, cultural and geographic parameters (1). for example, amphetamine abuse tends to be more common than ma in europe, except in czech republic, slovakia, estonia, and latvia. amphetamine is used therapeutically and illicitly in the united kingdom (3). ma, which is the second most popular illicit drug with an annual global prevalence estimated at 0.4% (3), is more dominant in the east, southeast asia and oceania (4). ats abuse is a serious health, social and economic problem all over the world. previous reports have determined the sigthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rahimi et al. 2 nificant correlation between ats abuse (mostly ma) via injection and risk of the transmission of blood-borne viruses (3). dependency and addiction are other mental and clinical health problems among ats abusers. dependence and chronic usage are associated with ma psychosis and other related psychosomatic and clinical adverse consequences (3). another health problem in ats abusers is acute poisoning, which is considered as a major problem in emergency settings (5, 6). the common features of ats poisoning include agitation, dilated pupils, tachycardia, hypertension, and tachypnea. other clinical findings include tremor, dyspnea, chest pain, hyperpyrexia and cardiac, hepatic and/or renal failure. coma or seizures occur less frequently (7). although there are reports about acute ats poisoning (8-11), to the best of our knowledge there are limited data about prognostic factors of mortality in acute ats poisoning cases (12, 13). therefore, the aim of the present study was to define the predictive factors of mortality in acute ats poisoning patients. 2. methods 2.1. study design and setting this is a retrospective cross-sectional study. all cases of pure acute ats poisoning, who were referred to the toxicology center of loghman hakim hospital, tehran, iran, since april 2011 to march 2014, were studied. this educational hospital serves as a referral center for poisoning patients of iranian capital, tehran. the study was approved by ethical committee of shahid beheshti university of medical sciences (grant no.: m-384). the authors adhered to the principles of helsinki declaration. the patients’ data were kept confidential. 2.2. participants all cases of pure acute ats poisoning who were admitted during the mentioned period were enrolled to the study using census sampling. the patients with co-ingestion or those discharged against medical advice were excluded. 2.3. data gathering using a self-made checklist, demographic data (sex, age), route of exposure, type and amount of ats, the cause of poisoning, history of addiction, clinical presentations, laboratory findings, electrocardiography (ecg) finding, duration of hospitalization, and outcomes (mortality, disposition, and complications during admission) were collected by a trained physician for all participants according to the patients’ medical records. we used icd10 classification for extracting patients’ medical records from the hospital’s archive. diagnosis of acute ats poisoning was done based on the history given by the patients or their relatives, physical examination and diagram 1: flow diagram of patient selection. ats: amphetamine type stimulants laboratory confirmation. 2.4. statistical analysis we used the social package for statistical analysis (spss) software version 16. the data were expressed as mean ± sd for continuous or discrete variables and as frequency and percentage for categorical variables. chi-square test was used for statistical analysis of qualitative variables. the normal distribution of quantitative variables was tested by kolmogorov – smirnov test. the statistical comparison was done with mann–whitney u -test for nonparametric variables and independent student t-test for parametric variables. logistic regression was used for evaluating the predictive factors of mortality. the best cut off points was determined by calculating the area under the receiver operating characteristics (roc) curve. p values of 0.05 or less were considered to be statistically significant and data were presented with 95% confidence interval (ci). 3. results 3.1. baseline characteristics 1722 ats intoxicated patients’ files were evaluated, out of which, 226 (13%) cases with acute ats poisoning were included (diagram 1). the mean age of the patients was 32.9 ± 10.9 (14 77) years (77% male). baseline characteristics, clinical presentations, and laboratory results, as well as ecg findings are summarized in table 1 and 2. the most common type of ats used was ma (97.4%) and the most frequent route of exposure was oral (55.3%). abuse was the most common cause of poisoning (66.8%) and the mean ats dose was 1.64 ± 1.59 grams. the mean time from exposure to admission was 5.9 ± 9.6 hours. history of addiction was positive in 123 (54%) cases with 5.3 ± 3.8 years mean duration of addiction. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e1 table 1: comparing the baseline characteristics of acute amphetamine type stimulants (ats) intoxicated patients who survived and those who died parameter total (n=226) survived (n=214) died (n=12) p value sex male 174 (77) 165 (77.1) 9 (75) 0.6 female 52 (23) 49 (22.9) 3 (25) type of ats methamphetamine 220 (97.4) 208 (97.2) 12 (100) mdma 1 (0.4) 1 (0.5) 0 0.9 methylphenidate 5 (2.2) 5 (2.3) 0 route of exposure oral 125 (55.3) 116 (54.2) 9 (75) inhalation 93 (41.2) 90 (42) 3 (25) injection 4 (1.8) 4 (1.9) 0 0.7 oral and inhalation 3 (1.3) 3 (1.4) 0 oral and injection 1 (0.4) 1 (0.5) 0 cause of poisoning abuse 151 (66.8) 146 (68.2) 5 (41.7) suicide 54 (23.9) 47 (22) 7 (58.3) accidental 2 (0.9) 2 (0.9) 0 0.7 body packer 15 (6.6) 15 (7) 0 body stuffer 4 (1.8) 4 (1.9) 0 ats dose (gram) 1.64±1.59 (0.5-13) 1.7±1.6 (0.5-13) 1.1±0.3 (1-1.5) 0.8 exposure to admission (hour) 5.9±9.6 (0.5-72) 6±9.8 (0.5-72) 4.4±3.1 (1-10) 0.9 duration of addiction (year) 5.3±3.8 (1-20) 5.3±3.9 (1-20) 5.5±3.1 (3-10) 0.9 age (year) 32.9±10.9 (14-77) 32.6±10.7 (14-77) 38.1±13.6 (19-55) 0.2 data were presented as mean ± standard deviation (minimum-maximum) or frequency (%). mdma: 3,4-methylendeoxymethamphetamine. 3.2. outcomes 19 (8.4%) cases were admitted to medical toxicology intensive care unit (icu) and others (207, 91.6% of cases) were admitted to general ward. in most of the cases (61.6%), the duration of hospitalization was ≤ 24 hours. intubation was indicated in 24 (10.6%) cases. the mortality rate was 5.4% (12/226). 2 cases of acute respiratory distress syndrome (0.9%), 2 ventilator associated pneumonia (0.9%), 2 rhabdomyolysis (0.9%), and 1 case of deep vein thrombosis (0.4%) were the complications detected in 7 (3.1%) patients (all of them were male). 3.3. predictive factors of mortality table 1 and 2 compare the baseline characteristics, clinical presentations, laboratory results, and ecg findings of acute ats poisoning among survived and non-survived cases. based on univariate analysis, there were significant associations between agitation (p = 0.002), seizure (p = 0.001), loss of consciousness on admission (p < 0.001), creatine phosphokinase level (p = 0.002), serum ph (p = 0.002), serum hco3 (p = 0.02), and pco2 (p = 0.01) with mortality. however, the results of multivariate regression analysis showed serum hco3 [or=1.27 (95% ci: 1.07-1.50); p value=0.005], pco2 [or=0.89 (95% ci: 0.84-0.96); p value=0.002], and loss of consciousness on admission [or=0.019 (95% ci: 0.003-0.106); p value=0.000] as the independent predictive factors of mortality in acute ats poisoning. based on the area under the roc curve (auc) the best cut off points of pco2 and serum hco3 for prediction of mortality were ≥ 51 mmhg [auc = 0.61 (95% ci: 0.401-0.822)] and ≤ 22.6 meq/l [auc = 0.704 (95% ci: 0.525-0.882)], respectively (figure 1). screening performance characteristics of pco2 ≥ 51 mmhg and hco3 ≤ 22.6 meq/l in prediction of acute ats intoxicated mortality are summarized in table 3. 4. discussion ats are potent psychostimulants that are abused all over the world (4). ats poisoning has recently emerged as a crucial health problem in clinical and forensic settings (8, 14, 15). therefore, the emergency department staff should be aware of the clinical presentations, paraclinical findings and prognostic factors of acute ats poisoning. in this study, the most common cause of poisoning was abuse and majority of cases, had oral exposure. in the previous study done in the same this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rahimi et al. 4 table 2: comparing the vital signs, clinical presentations, laboratory results, and electrocardiogram (ecg) findings among acute amphetamine type stimulants (ats) intoxicated patients who survived and those who died parameter total (n=226) survived (n=214) died (n=12) p value vital signs sbp (mmhg) 125.5±23.6 (80-230) 126±22.7 (80-230) 115.8±36.3 (80-180) 0.1 dbp (mmhg) 78.5±13.9 (40-150) 78.9±13.7 (50-150) 70±16.5 (40-100) 0.054 pulse rate (/minute) 99.2±19 (52-168) 99.2±18.5 (52-168) 99.8±27.1 (66-160) 0.6 clinical presentations agitation 172 (76.11) 168 (78.50) 4 (33.33) 0.002 confusion 66 (29.20) 65 (30.37) 1 (8.33) 0.09 judgment disorder 48 (21.24) 48 (22.43) 0 0.053 seizure 16 (7.08) 11 (5.14) 5 (41.67) 0.001 loc 16 (7.08) 9 (4.21) 7 (58.33) 0.000 hallucination 14 (6.19) 13 (6.0) 1(8.3) 0.6 diaphoresis 12 (5.31) 12 (5.31) 0 0.5 flushing 7 (3.1) 7 (3.1) 0 0.7 abdominal pain 5 (2.21) 5 (2.21) 0 0.8 blurred vision 2 (0.88) 2 (0.88) 0 0.9 laboratory findings sodium (meq/l) 140.1±5.0 (124-188) 140.1±5.0 (124-188) 140.1±5.1 (130-148) 1 potassium (meq/l) 4.1±0.5 (3-7.7) 4.1±0.5 (3.1-7.7) 4.2±0.9 (3-5.9) 0.5 cpk (u/l) 1067.9±2981.9 (28-30000) 813.2±1952.4 (28-17253) 7309.1±10263.3 (103-30000) 0.002 ldh (u/l) 909.1±841.3 (42-6033) 885.7±854.6 (42-6033) 1225±635.2 (563-2043) 0.1 serum ph 7.36±0.09 (6.90-7.90) 7.36±0.09 (6.90-7.90) 7.27±0.15 (6.90-7.40) 0.002 pco2 (mmhg) 43.9±9.8 (13-78) 43.6±9.2 (13-74) 51.2±16.5 (32-78) 0.01 serum hco3 (meq/l) 24.3±4.9 (8.7-56) 24.5±4.9 (8.7-56) 21.2±4.5 (15.8-28.4) 0.02 ecg findings normal sinus 104 (46) 97 (45.3) 7 (58.3) sinus tachycardia 103 (45.6) 100 (46.7) 3 (25.0) sinus bradycardia 8 (3.5) 7 (3.2) 1 (8.3) t inversion 10 (4.4) 9 (4.2) 1 (8.3) 0.3 qrs widening 7 (3.0) 6 (2.8) 1 (8.3) st change 4 (1.7) 3 (1.4) 1 (8.3) ventricular dysrhythmia 3 (1.3) 2 (0.9) 1 (8.3) hospitalization (hour) ≤24 139 (61.6) 132 (61.7) 7 (58.3) 0.07 >24 87 (38.4) 82 (38.3) 5 (41.7) data were presented as mean ± standard deviation (minimum-maximum) or frequency (%). sbp: systolic blood pressure, loc: loss of consciousness, dbp: diastolic blood pressure, cpk: creatine phosphokinase, ldh: lactate dehydrogenase; ecg: electrocardiogram. table 3: screening performance characteristics of pco2 ≥ 51 mmhg and serum hco3 ≤ 22.6 meq/l in predicting the risk of mortality in acute amphetamine type stimulants (ats) intoxicated patients character pco2 (95% ci) hco3 (95% ci) sensitivity 50.00 (22.28 – 77.71) 66.66 (35.43 – 88.72) specificity 78.97 (72.77 – 84.10) 72.89 (66.33 – 78.62) positive predictive value 11.76 (04.87 – 24.55) 12.12 (05.74 – 23.03) negative predictive value 96.57 (92.34 – 98.59) 97.50 (93.31 – 99.19) positive likelihood ratio 0.13 (0.06 – 0.28) 0.13 (0.07 – 0.26) negative likelihood ratio 0.03 (0.01 – 0.07) 0.02 (0.01 – 0.06) hospital, although the main cause of poisoning was abuse, the common route of exposure was inhalation (12). in our study, most of the patients were young men, which is in concordance with the results of previous studies (6, 12, 13). most of our patients had a positive history of addiction. this result is in line with previous studies (6, 12). ma was the most frequent type of ats used by our patients. the result is the same as previous studies in iran (12, 16), however, the studies in european countries showed amphetamine and mdma as the most frequent type of ats this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e1 figure 1: receiver operating characteristic (roc) curve for pco2 and serum hco3 in predicting the risk of mortality in acute amphetamine type stimulants (ats) intoxicated patients. among intoxicated cases (10, 17). this difference could be due to demographic variables such as marital status and level of education (18). previous studies introduced curiosity in trying different things and looking for pleasure as the most important reasons for ma abuse in iran (18, 19). other factors are lower effectiveness of previous drugs, popularity and low price of new drugs, and emulation of others (18, 20, 21). khodabandeh et al. reported ma abuse among methadone maintenance participants. the most common reasons were the good sensation, getting high, to enhance their sexual performance, and in some instances as self-medication for depression (22, 23). agitation, confusion and judgment disorder were the most common clinical manifestations. which are the same as the result of a previous study in australia (6). in another study in iran, loss of consciousness was the most common clinical finding, which could be due to co-ingestion with opioids and other drugs (12). most of the patients had abnormal ecg, and sinus tachycardia was the major finding, which has been reported previously (12, 24). the mortality rate was 5.4%, which was lower than previous studies (12, 13). this may be related to the delayed admission of the patients to the hospital in the previous studies (12). in our study, lower serum hco3, higher pco2 and low level of consciousness on admission were considered as predicting factors of mortality in ats poisoning cases. in the previous study performed in this center, age, history of suicide, route of poisoning and pulmonary manifestations on admission were considered as predictive factors of patient’s outcome (12), which is not supported by the results of our study. according to our results, pco2≥ 51 mmhg and serum hco3 ≤ 22.6 meq/l can predict the poisoned patients’ mortality rate with specificity (78.97% and 72.89%, respectively) and sensitivity (50.00% and 66.66%, respectively). however, based on the auc measures, serum hco3 can better discriminate between those who die and those who survive. we did not find a study that had evaluated the relationship between these laboratory findings and prediction of mortality. 5. limitation we evaluated the patients’ records retrospectively, which could be considered as a limitation of our study. 6. conclusion this study showed that high pco2, low serum bicarbonate and loss of consciousness on admission, could be associated with higher rate of mortality of acute ats intoxicated cases. 7. appendix 7.1. acknowledgements this article is the part of dr. somayeh lookzadeh’s thesis, who was an internal medicine resident at the time of the study. the authors wish to thank the nurses of loghman hakim hospital poisoning center; especially mrs. s. banajafari, the head nurse of mticu, mrs. m. rezvani and mrs. b. barari the staff of mticu. the authors would like to convey their full appreciation to toxicology research center for their financial support. 7.2. authors’ contribution all authors made a substantial contribution to analysis and writing of the paper draft and met the four criteria for authorship recommended by the international committee of medical journal editors. 7.3. funding/support this study was supported by a grant from toxicology research center, shahid beheshti university of medical sciences. grant number: m-384. 7.4. conflict of interest the authors declare that there is no conflict of interests regarding the publication of this paper. references 1. world health organization. amphetamine-type stimulants. available 1 august 2017. [available from: www.who.int/substance_abuse/facts/ats/en/. 2. kumar ms, kumar s. amphetamine type stimulants (ats) use in indiaan exploratory study. united nations this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rahimi et al. 6 office on drugs and crime (unodc); new delhi, india, 2015. 3. united nations office on drugs and crime (unodc), world drug report, vienna, 2015. 4. united nations office on drugs and crime (unodc), the challenge of synthetic drugs in east and south-east asia and oceania, vienna, may 2015. 5. alam mehrjerdi z, noroozi a. methamphetamine intoxication in emergency departments of hospitals in iran: implications for treatment. iran j med sci. 2013;38(4):347-8. 6. bunting pj, fulde gw, forster sl. comparison of crystalline methamphetamine ("ice") users and other patients with toxicology-related problems presenting to a hospital emergency department. med j australia. 2007;187(10):564-6. 7. cruickshank cc, dyer kr. a review of the clinical pharmacology of methamphetamine. addiction. 2009;104(7):1085-99. 8. yazdani mr tn, masoumi gr, gheshlaghi f, dana-siadat z, setareh m, et al. demographic factors, duration and costs of hospitalization, and causes of death in patients intoxicated with opioids and amphetamines. international journal of medical toxicology and forensic medicine. 2014;4(4):122-9. 9. hassanian-moghaddam h, zamani n, rahimi m, shadnia s, pajoumand a, sarjami s. acute adult and adolescent poisoning in tehran, iran; the epidemiologic trend between 2006 and 2011. arch iran med. 2014;17(8):534-8. 10. le roux g bc, lelievre b, bretaudeau deguigne m, turcant a, harry p, et al. recreational phenethylamine poisonings reported to a french poison control center. drug alcohol depend 2015;154:46-53. 11. jones aw ha. amphetamine abuse in sweden: subject demographics, changes in blood concentrations over time, and the types of co-ingested substances. j clin psychopharmacol. 2013;33(2):48-52. 12. paydar p, sabzghabaee am, paydar h, eizadi-mood n, joumaa a. outcome of treatment in patients with methamphetamine poisoning in an iranian tertiary care referral center. j res pharm pract. 2015;4(3):167-72. 13. lan kc, lin yf, yu fc, lin cs, chu pl. clinical manifestations and prognostic features of acute methamphetamine intoxication. j formos med assoc. 1998;97(8):528-33. 14. schifano f, corkery j, naidoo v, oyefeso a, ghodse h. overview of amphetamine-type stimulant mortality data uk, 1997-2007. neuropsychobiology. 2010;61(3):122-30. 15. arendt m, munk-jorgensen p, sher l, jensen sow. mortality among individuals with cannabis, cocaine, amphetamine, mdma, and opioid use disorders: a nationwide follow-up study of danish substance users in treatment. drug alcohol depen. 2011;114(2-3):134-9. 16. behnoush b, taghadosinejad f, arefi m, shahabi m, jamalian m, kazemifar am. prevalence and complications of drug-induced seizures in baharloo hospital, tehran, iran. iran j toxicol. 2012;6(16):588-93. 17. dines am, wood dm, yates c, heyerdahl f, hovda ke, giraudon i, et al. acute recreational drug and new psychoactive substance toxicity in europe: 12 months data collection from the european drug emergencies network (euro-den). clin toxicol (phila). 2015;53(9):893900. 18. barati m, ahmadpanah m, soltanian ar. prevalence and factors associated with methamphetamine use among adult substance abusers. j res health sci. 2014;14(3):2216. 19. shams alizadeh n, moghadam m, mohsenpour b, rostami gooran n. prevalence of substance abuse in medical students of kurdistan university. scientific j kurdistan uni med sci. 2008;13(2):18-28. 20. farhadinasab a, allahverdipour h, bashirian s, mahjoub h. lifetime pattern of substance abuse, parental support, religiosity, and locus of control in adolescent and young male users. iran j public health. 2008;37(4):88-95. 21. doaghoyan d, habibzadeh maleki a. factors influencing the changing patterns of drug use among young people, from light drug to heavy drug. j disciplinary knowledge. 2011;13(1):105-33. 22. khodabandeh f, kahani s, shadnia s, abdollahi m. comparison of the efficacy of methadone maintenance therapy vs. narcotics anonymous in the treatment of opioid addiction: a 2-year survey. int j pharmacol. 2012;8:4459. 23. shariatirad s, maarefvand m, ekhtiari h. methamphetamine use and methadone maintenance treatment: an emerging problem in the drug addiction treatment network in iran. int j drug policy. 2013;24(6):e115-6. 24. smets g, bronselaer k, de munnynck k, de feyter k, van de voorde w, sabbe m. amphetamine toxicity in the emergency department. eur j emerg med. 2005;12(4):193-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e13 or i g i n a l re s e a rc h vitamin d status in epileptic children on valproic acid; a case-control study ameena taha abdullah1∗, zaher taher mousheer1 1. raparin pediatric hospital, hawler medical university, college of medicine, erbil, iraq. received: january 2020; accepted: february 2020; published online: 27 february 2020 abstract: introduction: much attention has been paid to the association between valproic acid treatment and bone health. the objective of this study is to compare the serum vitamin d3 level in the epileptic children under valproic acid treatment with the healthy control group. methods: a case-control study has been carried out to compare vitamin d3 levels in 50 epileptic children who were treated with valproic acid with 50 healthy children selected from children visiting the hospital for routine checkup as control group. results: 100 cases with the mean age of 7.57± 3.62 years (range: 2 – 15 years) were studied (44% boys). among the 50 epileptic cases; 41 (82%) had generalized and 9 (18%) had partial seizure (56% well controlled and 44% poorly controlled). 15 (30%) of epileptic cases were using anti-epileptic drugs for 6-12 months, 36% for 12-24 months, and 34% for more than 24 months. the case and control groups were similar regarding gender (p =0.99), age (p = 0.24), and bmi (p = 0.64). 49 (49%) patients had some grade of vitamin d3 deficiency. there was a significant difference between case and control groups regarding vitamin d3 levels (p = 0.001). none of the controls had severe vitamin d3 deficiency, while 14% of cases did. 36 (72%) individuals in control group had sufficient or optimal vitamin d3 levels; while only 15 (30%) case patients had such levels. generally, the control group had higher vitamin d3 levels in comparison to case group (p = 0.001). conclusion: the study revealed that there was a higher prevalence of vitamin d3 insufficiency in epileptic children receiving valproate monotherapy compared with healthy children. vitamin d3 supplementation should be given to all epileptic children even before initiation of anti-epileptic drugs. keywords: epilepsies, myoclonic; valproic acid; cholecalciferol (vitamin d3) cite this article as: taha abdullah a, taher mousheer z. vitamin d status in epileptic children on valproic acid; a case-control study. arch acad emerg med. 2020; 8(1): e13. 1. introduction epilepsy is defined as a condition of susceptibility to recurrent seizures, when at least two or more unprovoked seizures occur more than 24 hours apart (1). the clinical diagnosis of epilepsy usually requires the occurrence of at least one unprovoked epileptic seizure with either a second seizure or enough electroencephalogram (eeg) and clinical information to convincingly demonstrate an enduring predisposition to develop recurrences. antiepileptic drugs are used for prevention of seizure; carbamazepine, sodium valproate, phenytoin and phenobarbitone are commonly used antiepileptic drugs (2). the effects of antiepileptic drugs on vitamin d3 levels have been studied for more than 40 years ∗corresponding author: ameena taha abdullah, raparin pediatric hospital, erbil, iraq. email: ameenaabdullah.900@gmail.com, tel: +964 7504211377 (3, 4). most of the antiepileptic drugs are inducers of hepatic cyp450 metabolism. these antiepileptic drugs result in increased hepatic metabolism of vitamin d leading to low vitamin d3 levels. however, some non-enzyme inducing antiepileptic drugs (e.g. valproic acid) have also been associated with low vitamin levels, which cause poor bone health (5). much attention has been paid to the association between valproic acid treatment and bone health over the last few years. a recent study revealed that treatment with valproic acid could lead to a decrease in vitamin d3 levels in pediatric epileptic patients, which explained the adverse bone-related side effects of valproic acid therapy (6). vitamin d is an important prohormone, which plays roles in metabolism of calcium, strengthening the bones and other metabolic processes (7, 8). approximately 1% of the population is on long-term and sometimes lifelong antiepileptic drug therapy and therefore, exposed to the potential metabolic side-effects of these this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. taha abdullah et al. 2 drugs. these adverse effects are changes in homocysteine, lipoproteins and vitamin d metabolism (9). multiple health outcomes are dependent on an adequate vitamin d3 level. vitamin d is very important for proper growth and development of bones in children. type, dosage and duration of antiepileptic drugs determine the extent of osteopathy (10). vitamin d3 deficiency is a worldwide condition (11). about one billion people in the world have vitamin d3 insufficiency or deficiency (<30 ng/ml) (12). the most important cause of vitamin d3 deficiency is long-term use of antiepileptic drugs in epileptic children (13, 14). since they need longterm anticonvulsant therapy, they have a high risk for showing side effects (15). long-term use of anticonvulsant medications has been associated with high incidence of rickets, higher risk of fracture, and decreased bone mineral density (16, 17). vitamin d3 supplementation is associated with decreased frequency of seizures, because it regulates proconvulsant and anticonvulsant factors; also vitamin d is involved in the down regulation of cytokine il-6, which is a proconvulsant (18). the objective of the study is to compare the serum vitamin d3 levels of the epileptic group, who were treated with valproic acid, with the healthy group as control. 2. methods 2.1. study design and setting this retrospective case-control study has been carried out to determine the serum level of vitamin d3 in 50 epileptic children who were treated with a single antiepileptic drug (valproic acid) and compare it with the control group comprised of 50 children with normal growth parameters selected from those attending the pediatric clinic at raparin pediatric hospital in erbil city, kurdistan region, iraq, from march 1st, 2019 to september 1st, 2019 (six month). the protocol of the study was approved by the research ethics committee of kurdistan board for medical specialties (ethics code: iraq.kbms.2019.177). informed consent (oral and written) was taken from all child parents. 2.2. participants all the children had normal age-appropriate development. the case group included epileptic children 2-15 years old under regular treatment with valproic acid for 6 months or more. children with neurological deficits like cerebral palsy or mental retardation, children with episodes of febrile convulsion, epileptic children who are seizure free and have stopped taking medication for three or more years, children with chronic diseases like renal, hepatic, endocrine or metabolic bone diseases, and children with vitamin d3 supplementation were excluded from the study. 2.3. data gathering a questionnaire was designed for the study including: identity; name, date of birth, sex, and body mass index (bmi), which was calculated by weight in kilograms divided by the height in square meters (18). according to centers for disease control and prevention (cdc) chart, the underweight is less than the 5th percentile; normal weight between 5th-85th percentile and overweight is more than 85th percentile. history of epilepsy; type and frequency of seizures over the last 3 months, to define well or poorly controlled cases, (well controlled case was defined as seizures free for the last 3 months) (1), and duration of the antiepileptic drugs was taken (20). 2.4. vitamin d3 level measurement two milliliters of peripheral venous blood was drawn from the child. samples were sent to laboratory of raparin teaching hospital and analysis was done for 25-hydroxy vitamin d level via elisa test. severe vitamin d3 deficiency was defined as a level less than <5 ng/ml; deficiency was defined as the level between (5-15 ng/ml); insufficiency was defined as the level between (15-20 ng/ml); and between (20-30 ng/ml) vitamin d was deemed sufficient. optimal level was defined as the level between (30-50 ng/ml) and upper normal was defined as the level between (50-70 ng/ml). 2.5. statistical analysis the statistical package for the social sciences program version 24 (spss, ibm company, chicago, il, usa), was used for data analysis. findings were reported as mean ± standard deviation or frequency (%). the results were analyzed using frequency distribution and t-test and chi square or fisher’s exact tests if necessary. p-value of ≤ 0.05 was considered as statistically significant. sample size was calculated using epi infot m version 7. 3. results 3.1. baseline characteristics of cases 100 cases with the mean age of 7.57± 3.62 (range: 2 – 15) years were studied (44% boys). table 1 shows the baseline characteristics of studied cases. among the 50 epileptic cases 41 (82%) had generalized and 9 (18%) had partial seizure (56% of the seizures were well controlled and 44% poorly controlled). 15 (30%) of epileptic cases were using anti-epileptic drugs for 6-12 months, 36% for 12-24 months, and 34% for more than 24 months. table 2 compares the baseline characteristics as well as vitamin d3 levels between case and control groups. the case and control groups were similar regarding gender (p =0.99), age (p = 0.24), and bmi (p = 0.64). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e13 table 1: baseline characteristics of studied cases variables number (%) gender girl 56 (56.0) boy 44 (44.0) age (year) 2-5 33 (33.0) 5-10 38 (38.0) 10-15 29 (29.0) body mass index < 50 41 (41) 50-85 38 (38) >85 21 (21) vitamin d level severe deficiency 7 (7.0) deficiency 21 (21.0) insufficiency 21 (21.0) sufficient 28 (28.0) optimal 23 (23.0) 3.2. vitamin d3 levels 49 (49%) patients had some grade of vitamin d3 deficiency. there was a significant difference between case and control group regarding vitamin d3 levels (p = 0.001). none of the controls had severe vitamin d3 deficiency, while 14% of cases did. 36 (72%) controls had sufficient or optimal vitamin d3 levels; while only 15 (30%) cases had such levels. generally, the controls had higher vitamin d3 levels in comparison to cases (p = 0.001). 4. discussion in this study, we observed that the level of vitamin d3 was significantly lower among epileptic children on valproic acid monotherapy compared to healthy children, a similar result was concluded by khadum et al. and rafiq et al. (21, 22). in our study, we revealed that more than two third of patients had sub optimal vitamin d3 level, while less than one third of them had optimal vitamin d3 level; this result is in agreement with menon et al. study (23). there was no significant statistical association between study group (case or control) and age or bmi of children with decreased level of vitamin d3. this is in agreement with alison et al. study (24) and in contrast to a previous study done by baek et al. (25), which showed that the level of vitamin d3 decreases with increase in bmi (children with high bmi have a high body fat, which acts as a reservoir for lipid-soluble vitamin d). our study showed that epileptic girls had lower vitamin d3 levels than boys. other studies of the population, which included healthy children also showed lower levels of vitamin d3 and a higher frequency of vitamin d3 deficiency in girls compared to boys (11). unfortunately, our study does not explain the reason for this finding but it could be due to the difference in the amount of sun exposure as the duration of outdoor activities is shorter in girls compared to boys. the current study revealed that there is a significant association between the non-enzyme inducing antiepileptic drug sodium valproate and vitamin d3 level; this can be explained through the enzyme inhibiting effect of valproic acid, which affects vitamin d3 metabolism. this result is in agreement with xu et al. study (6) . routine monitoring of vitamin d level is warranted to prevent vitamin d3 deficiency in epileptic children on chronic valproate therapy. vitamin d3 supplementation should be given to all epileptic children, even before initiation of antiepileptic drugs, and these patients should follow a well-balanced diet and healthy lifestyle to optimize seizure control. 5. limitation our study had some limitations, the main one being that vitamin d3 levels were not measured before starting valproic acid therapy and hence, we cannot categorically attribute the levels to antiepileptic drug use. second, we did not assess bone density in both cases and controls due to both financial reasons and lack of a standardized reference range for children. third, sample size was small. fourth, we did not study the participants’ lifestyle, like diet, activity and sunlight exposure, which might have affected vitamin d3 level. strengths of our study were that we recruited cases and controls from the same hospital; thus, reducing difference based on ethnicity, social customs and socioeconomic status. additionally, the present study has a retrospective design, which has limitations in its nature such as missing data. short duration of study, not following the patients, and being a single centered study were among other limitations of the study. 6. conclusion the study revealed that there is a higher prevalence of vitamin d3 insufficiency in epileptic children under valproate monotherapy compared with healthy children. further studies are warranted to determine other important factors that contribute to low vitamin d3 levels in children on valproate therapy. 7. declarations 7.1. acknowledgements we thank the registration staff members of raparin teaching hospital for their hearty cooperation and helping us perform this study. 7.2. author contribution all the authors met the criteria recommended by the international committee of medical journal editors for gaining this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. taha abdullah et al. 4 table 2: comparing the baseline characteristics as well as vitamin d level between case and control groups variables study groups p-value case (n = 50) control (n = 50) gender girl 28 (56) 28 (56) 0.99 boy 22 (44) 22 (44) age (year) 2-5 15 (30.0) 18 (36.0) 5-10 23 (46.0) 15 (30.0) 0.24 10-15 12 (24.0) 17 (34.0) bmi < 50 21 (42.0) 20 (40.0) 50-85 17 (34.0) 21 (42.0) 0.64 >85 12 (24.0) 9 (18.0) vitamin d level severe deficiency 7 (14.0) 0 (0.0) deficiency 14 (28.0) 7 (14.0) insufficiency 14 (28.0) 7 (14.0) 0.001 sufficient 6 (12.0) 22 (44.0) optimal 9 (18.0) 14 (28.0) bmi: body mass index. authorship. authors orcids ameena taha abdullah: 0000-0002-9953-0436 zaher taher mousheer: 0000-0003-3582-298x 7.3. funding/support there was no funding and support. 7.4. conflict of interest there are no conflicts of interest. references 1. friedman mj, sharieff gq. seizures in children. pediatric clinics of north america. 2006;53(2):257-77. 2. abbott mb, vlasses chjj. nelson textbook of pediatrics. 2011;306(21):2387-8. 3. hunter j, maxwell jd, stewart da, parsons v, williams r. altered calcium metabolism in epileptic children on anticonvulsants. british medical journal. 1971;4(5781):2024. 4. dent ce, richens a, rowe dj, stamp tc. osteomalacia with long-term anticonvulsant therapy in epilepsy. british medical journal. 1970;4(5727):69-72. 5. erbayat altay e, serdaroglu a, tumer l, gucuyener k, hasanoglu a. evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. journal of pediatric endocrinology & metabolism : jpem. 2000;13(7):933-9. 6. xu z, jing x, li g, sun j, guo h, hu y, et al. valproate decreases vitamin d levels in pediatric patients with epilepsy. seizure. 2019;71:60-5. 7. wagner cl, greer fr. prevention of rickets and vitamin d deficiency in infants, children, and adolescents. pediatrics. 2008;122(5):1142-52. 8. valsamis ha, arora sk, labban b, mcfarlane si. antiepileptic drugs and bone metabolism. nutrition & metabolism. 2006;3(1):36. 9. nettekoven s, strohle a, trunz b, wolters m, hoffmann s, horn r, et al. effects of antiepileptic drug therapy on vitamin d status and biochemical markers of bone turnover in children with epilepsy. european journal of pediatrics. 2008;167:1369-77. 10. bartl r. [antiepileptic drug-induced osteopathy. subtypes, pathogenesis, prevention, early diagnosis and treatment]. deutsche medizinische wochenschrift (1946). 2007;132(27):1475-9. 11. zhu z, zhan j, shao j, chen w, chen l, li w, et al. high prevalence of vitamin d deficiency among children aged 1 month to 16 years in hangzhou, china. bmc public health. 2012;12:126. 12. khor gl, chee ws, shariff zm, poh bk, arumugam m, rahman ja, et al. high prevalence of vitamin d insufficiency and its association with bmi-for-age among primary school children in kuala lumpur, malaysia. bmc public health. 2011;11:95. 13. holick mf. vitamin d deficiency. the new england journal of medicine. 2007;357(3):266-81. 14. fitzpatrick la. pathophysiology of bone loss in patients receiving anticonvulsant therapy. epilepsy & behavior : e&b. 2004;5 suppl 2:s3-15. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e13 15. petty sj, o’brien tj, wark jd. anti-epileptic medication and bone health. osteoporosis international : a journal established as result of cooperation between the european foundation for osteoporosis and the national osteoporosis foundation of the usa. 2007;18(2):129-42. 16. drezner mk. treatment of anticonvulsant drug-induced bone disease. epilepsy & behavior : e&b. 2004;5 suppl 2:s41-7. 17. cansu a, yesilkaya e, serdaroglu a, hirfanoglu t, camurdan o, gãijlbahar o, et al. evaluation of bone turnover in epileptic children using oxcarbazepine. pediatric neurology. 2008;39:266-71. 18. wortsman j, matsuoka ly, chen tc, lu z, holick mf. decreased bioavailability of vitamin d in obesity. the american journal of clinical nutrition. 2000;72(3):690-3. 19. killingsworth cr, wei c-c, dell’italia lj, ardell jl, kingsley ma, smith wm, et al. short-acting îš-adrenergic antagonist esmolol given at reperfusion improves survival after prolonged ventricular fibrillation. circulation. 2004;109(20):2469-74. 20. bozzetto s, carraro s, giordano g, boner a, baraldi e. asthma, allergy and respiratory infections: the vitamin d hypothesis. allergy. 2012;67(1):10-7. 21. habeeb s, hameed r. 25-hydroxy vitamin d in children with epilepsy in basra. international journal of current research. 2017;9:international journal of current research. 22. rafiq m, bano s, tariq patajpjop. effects of antiepileptic drug therapy on 25oh vitamin d levels. 2015;11(4):24-6. 23. menon b, harinarayan cv. the effect of anti epileptic drug therapy on serum 25-hydroxyvitamin d and parameters of calcium and bone metabolism–a longitudinal study. seizure. 2010;19(3):153-8. 24. pack am. the association between antiepileptic drugs and bone disease. epilepsy currents. 2003;3(3):91-5. 25. baek jh, seo yh, kim gh, kim mk, eun bl. vitamin d levels in children and adolescents with antiepileptic drug treatment. yonsei medical journal. 2014;55(2):417-21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e48 or i g i n a l re s e a rc h use of a motorlance to deliver emergency medical services; a prospective cross sectional study korakot apiratwarakul1,2, kamonwon ienghong1∗, thapanawong mitsungnern1, praew kotruchin1, pariwat phungoen1, vajarabhongsa bhudhisawasdi1 1. department of emergency medicine, faculty of medicine, khon kaen university, khon kaen, thailand. 2. research group for emergency patients care and emergency medical services, faculty of medicine, khon kaen university, khon kaen, thailand. received: june 2019; accepted: july 2019; published online: 21 august 2019 abstract: introduction: access time to patients with critical or emergent situations outside the hospital is a critical factor that affects both severity of injury and survival. this study aimed to compare the access time to the scene of an emergency situation between a traditional ambulance and motorlance. methods: this prospective cross sectional study was conducted on all users of emergency call, srinagarind hospital, thailand, from june to december 2018, who received a registration number from the command center. results: 504 emergency-service operations were examined over a six-month period, 252 (50%) of which were carried out by motorlance. the mean activation time for motorlance and ambulance were 0.57 ± 0.22 minutes and 1.11 ± 0.18 minutes, respectively (p<0.001). mean response time for motorlance was significantly lower (5.57 ± 1.21 versus 7.29 ± 1.32 minutes; p < 0.001). the response times during 6 a.m. to 6 p.m. were 5.26 ± 1.11 minutes for motorlance and 7.15 ± 1.39 minutes for ambulance (p < 0.001). these measures for night time (6 p.m. to 6 a.m.) were 5.58 ± 1.21 minutes and 8.01 ± 1.30 minutes, respectively (p < 0.001). the mean automated external defibrillator (aed) waiting time for motorlance and ambulance were 5.26 ± 2.36 minutes and 9.24 ± 3.30 minutes, respectively (p = 0.012). the survival rate of patients after aed use in motorlance and ambulance was 80% versus 37.5%; p<0.001. conclusion: emergency service delivery by motorlance had lower mean activation time, response time, aed time, and mortality rate of cardiac arrest patients compared to ambulance. it seems that motorlance could be considered as an effective and applicable device in emergency medical service delivery, especially in crowded cities with heavy traffic. keywords: emergency medicine; emergency medical services; ambulances; emergency mobile units cite this article as: apiratwarakul k, ienghong k, mitsungnern t, kotruchin p, phungoen p, bhudhisawasdi v. use of a motorlance to deliver emergency medical services; a prospective cross sectional study. arch acad emerg med. 2019; 7(1): e48. 1. introduction the access time of emergency medical services (ems), to people who are injured or suffer from cardiac arrest is a critical factor that affects both severity of injury and survival (1-3). the use of traditional ambulances to reach people in emergency situations in large cities with traffic problems can result in delayed access times (4, 5). at present, there are efforts to choose vehicles that are flexible and can reduce access times such as motorcycles equipped with medical devices (motorlance) (6-8). advanced emergency med∗corresponding author: kamonwon ienghong; department of emergency medicine, faculty of medicine, khon kaen university, khon kaen, thailand 40002 email: kamonwan@kku.ac.th, tel: +6643366869, fax: +6643366870 ical technicians (aemts) are responsible for driving the vehicle, which is able to measure oxygen saturation, check vital signs, and perform basic airway management and cardiopulmonary resuscitation (cpr). the driver must pass a motorcycle driving test administered at a standard training center and must use proper safety equipment at all times. in order to synchronize information with the command center, a headset-based radio is used, and the helmet microphone acts as a communication device. a motorlance can be used to send a doctor or nurse to the scene of severe traffic accidents quickly to administer treatment and deliver medical supplies such as blood or drugs (9). a previous study found that using a motorlance can reduce access times to injured persons in both urban and rural areas (10-13). however, there have been no studies about motorlance use in thailand. the obthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. apiratwarakul et al. 2 jective of the present study was to compare the access time to the scene of an emergency situation between a traditional ambulance and motorlance. 2. methods 2.1. study design and setting in this prospective cross sectional study, all users of emergency call (via emergency telephone number 1669 in thailand operation), at srinagarind hospital, thailand, from june 2018 to december 2018, who receive a registration number from the command center were evaluated. the present study protocol was approved by khon kaen university ethics committee for human research (he611219). requirement for informed consent from the patients was waived since patient confidentiality protection had been guaranteed, as patients were not identified by name, but by a unique study number. 2.2. participants data of all patients aged over 18 years were collected. cases in which the patient was being referred between hospitals and patients with missing data were excluded from this study. 2.3. data gathering data were recorded using a standard national operation checklist for emergency medical services in thailand consisting of demographic data (age, gender), operation time (day, night), type of patients (trauma, non-trauma), type of first procedure on scene for all patients, time stayed in emergency room, duration of hospital stay and outcome of patients with cardiac arrest who were referred by ambulance or motorlance. a trained emergency medicine resident was responsible for data gathering under direct supervision of an emergency medicine specialist. 2.4. definitions times from dispatch to resources being en route was defined as activation time and response time was defined as time from 1669 center call receipt to arrival on scene. time from dispatch to aed arrival on scene was defined as aed waiting time. 2.5. statistical analysis the sample size was calculated based on the standard deviation of access time detailed in a previous study by peyravi (13). in order to achieve a significance level of 5% and power of test of 0.8, we determined that a sample size of 504 would be required. statistical analysis was performed using spss for windows version 16.0 (spss inc., chicago, il, usa). categorical data were presented as percentage, and continuous data were presented using mean and standard deviation. univariate analysis was performed using two-sample t-test for numerical data and chi-squared test for comparing data between the groups. 3. results 3.1. baseline characteristics of the subjects and services five hundred four emergency-service operations were examined over a six-month period, 252 (50%) of which were carried out by motorlance. the characteristics of the subjects and services are shown in table 1. the most common time of day at which motorlance was deployed was during the afternoon shift (4 p.m. to 0.00 a.m.; 52.0%). the most common first procedure performed on scene was breathing management. the procedure was performed in 41.3% of cases in the motorlance group compared with 43.6% in the ambulance group (p=0.359). 3.2. outcomes table 2 compares the outcomes between emergency services carried out by motorlance and ambulance. the mean activation time, mean response time (p<0.001), and mean automated external defibrillator (aed) waiting time (p = 0.012) were significantly lower in patients who were referred to ed by motorlance. the survival rate of cardiac arrest cases was significantly higher in motorlance group (80% versus 37.5%; p<0.001). there as not any difference between groups regarding duration of ed (p > 0.05) and hospital stays (p > 0.05). 4. discussion based on the findings of the present study, emergency service delivery by motorlance had lower mean activation time, response time, aed time, and mortality rate of cardiac arrest patients compared to ambulance. thailand’s emergency medical services (ems) was established to allow equipment and medical staff to be deployed to manage and treat emergency patients en route using a traditional ambulance. emergency medical responders (emrs), emergency medical technicians (emts), advanced emergency medical technicians (aemts), and paramedics are deployed through this service. physicians are in short supply and mainly provide services in the emergency room and command center with online medical oversight (11). thailand will enter the 4.0 era in accordance with government policy. public health development is a branch that must develop for taking care of people with international standards. caring for patients who are injured at the scene through the operation of emergency medical services is important to reduce the mortality rate (14). response and activation times are key factors in accessing emergency patients. in major cities, traffic congestion can negatively affect the arrival time of emergency services to the scene of an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e48 table 1: characteristics of the subjects and services variable motorlance (n=252) ambulance (n=252) p value age (years) mean ± sd 40.29 ± 12.75 39.25 ± 11.12 0.720 median (25t h 75t h percentile) 40 (28, 50) 39 (27, 48) gender male 123 (48.8) 147 (58.3) 0.548 female 129 (51.2) 105 (41.7) operation time (shift) 8 a.m. to 4 p.m. 84 (33.3) 80 (31.7) 4 p.m. to 0.00 a.m. 131 (52.0) 135 (53.6) 0.326 0.00 a.m. to 8.00 a.m. 37 (14.7) 37 (14.7) type of patients non-trauma 109 (43.2) 112 (44.4) 0.662 trauma 143 (56.8) 140 (55.6) first procedure on scene airway management 60 (23.8) 63 (25.0) 0.675 breathing 104 (41.3) 110 (43.6) 0.359 circulation 31 (12.3) 37 (14.7) 0.211 immobilization 57 (22.6) 42 (16.7) 0.042* data are presented as mean ± standard deviation (sd) or number (%). table 2: comparing the outcome between emergency services carried out by motorlance and ambulance variable motorlance (n=252) ambulance (n=252) p value activation time (minutes) mean ± sd 0.57 ± 0.22 1.11 ± 0.18 p<0.001 response time (minutes) mean ± sd 5.57 ± 1.21 7.29 ± 1.32 < 0.001 6 a.m. to 6 p.m. 5.26 ± 1.11 7.15 ± 1.39 < 0.001 6 p.m. to 6 a.m. 5.58 ± 1.21 8.01 ± 1.30 < 0.001 duration of ed stay < 1 hour 42 (16.7) 38 (15.1) 0.677 > 1 hour 210 (83.3) 214 (84.9) 0.680 duration of hospital stay 1 day 12 (4.8) 15 (6.0) 0.450 2 days 25 (9.9) 22 (8.7) 0.570 3 days 30 (11.9) 28 (11.1) 0.680 > 3 days 185 (73.4) 187 (74.2) 0.710 aed waiting time* (minutes) mean ± sd 5.26 ± 2.36 9.24 ± 3.30 0.012 mortality* survived 8 (80.0) 9 (37.5) <0.001 not survived 2 (20.0) 15 (62.5) * for patients with cardiac arrest. aed: automated external defibrillator; ed: emergency department. times from dispatch to resources being en route was defined as activation time and response time was defined as time from 1669 center call receipt to arrival on scene. times from dispatch to aed arrival on scene defined as aed waiting time. emergency. motorlance can, thus, be used to reduce arrival times and increase the efficiency of emergency medical services. although there are several medical emergency systems around the world that use motorlance, few studies have been published that evaluate their effectiveness (1). the main objective of using motorlance is to reduce the time it takes to administer treatment in critical situations. our study, which examined 504 cases over a six-month period, found that the average motorlance response time was shorter than that of traditional ambulances (5.57 versus 7.29 minutes), a result that is consistent with those of previous studies conducted in various countries (5-8). response time and use for standard emergency medical services is related to the infrastructure of the city and the availability of different hospitals combined with low traffic congestion (10). in thailand, the maximum this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. apiratwarakul et al. 4 response time in resuscitation cases is set at eight minutes. the use of a motorlance allowed us to achieve this goal. in addition, emergency medical services need to reach patients quickly to assess symptoms and provide treatment. medical staff will operate by using an ambulance as a travel vehicle, the signal lights and the siren sound of ambulance cause drivers to make way for ambulance (15). after delivery to hospital, the time that patients stayed in emergency room (er), which depends on many steps of work (time to doctor visit, overcrowding in er, blood test waiting time), was not different between motorlance and traditional ambulance; a result that is consistent with those of previous studies (16), which showed patient disposition, especially admission, investigation and triage level were the main factors leading to longer periods in emergency department. of course, the duration of hospital stay also depends on multiple factors including severity of disease. in cardiac arrest patients, aed waiting time was shorter in motorlance group (5.26 versus 9.24 minutes), resulting in a higher survival rate among patients after aed use in motorlance compared to ambulance (80% versus 37.5%). basic life support (bls) and aed usage is one of the first aid procedures that general population can legally perform in thailand. teaching these procedures to the general population will increase survival rate of cardiac arrest patients (17). as a result of this study, the national institute for emergency medicine (niem), which is responsible for administrative management and coordination between relevant agencies in both public and private sectors, will promote the use of motorlance for delivering emergency medical services in thailand. 5. limitation the use of the motorlance was limited in some weather conditions (heavy rain). it should be noted that in the current study, data were gathered from only one emergency medical service center. 6. conclusion emergency service delivery by motorlance had lower mean activation time, response time, aed time, and mortality rate of cardiac arrest patients compared to ambulance. it seems that motorlance could be considered as an effective and applicable device in emergency medical service delivery, especially in crowded cities with heavy traffic. 7. appendix 7.1. acknowledgements the authors would like to thank sumitr sukwiset (1977-2017), the first motorlance driver, kaewjai thepsuthammarat for her data analysis and statistical review, and dylan southard for acting as english consultant. 7.2. author contribution all authors met the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids korakot apiratwarakul: 0000-0002-1984-0865 kamonwon ienghong: 0000-0003-0328-4128 thapanawong mitsungnern: 0000-0002-5046-5151 praew kotruchin: 0000-0003-3519-3415 pariwat phungoen: 0000-0003-3631-0679 7.3. funding/support the present study received funding from the khon kaen university, faculty of medicine (in61238). 7.4. conflict of interest the authors declare no conflict of interest. references 1. pons pt, haukoos js, bludworth w, cribley t, pons ka, markovchick vj. paramedic response time: does it affect patient survival? academic emergency medicine. 2005;12(7):594-600. 2. soares-oliveira m, egipto p, costa i, cunha-ribeiro lm. emergency motorcycle: has it a place in a medical emergency system? the american journal of emergency medicine. 2007;25(6):620-2. 3. vukmir rb. survival from prehospital cardiac arrest is critically dependent upon response time. resuscitation. 2006;69(2):229-34. 4. lin c-s, chang h, shyu k-g, liu c-y, lin c-c, hung c-r, et al. a method to reduce response times in prehospital care: the motorcycle experience. the american journal of emergency medicine. 1998;16(7):711-3. 5. peleg k, pliskin js. a geographic information system simulation model of ems: reducing ambulance response time. the american journal of emergency medicine. 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prehospital care time intervals among victims of road traffic injuries in iran. a cross-sectional study. bmc public health. 2010;10(1):406. 11. chinprasatsak s, satthapong s, kotruchin p, maporn k. telegraphic medicine systems improve medical diagnosis in pre-hospital settings: a pilot study in a tertiary care hospital. j med assoc thai. 2017;100(6):686-91. 12. kiefe cc, soares-oliveira m. medical emergency motorcycles: are they safe? european journal of emergency medicine. 2008;15(1):40-2. 13. peyravi mr, tubaei f, pourmohammadi k. the efficiency of motorlance in comparison with ambulance in shiraz, southern iran. iranian red crescent medical journal. 2009;11(3):330. 14. apiratwarakul k. development of emergency medical service. srinagarind medical journal. 2017;32(3):289-94. 15. apiratwarakul k, artpru r, ienghong k, rattanaseeha w, piwhom t, phungoen p. the study of driving behavior when encounter the light and siren on ambulance. srinagarind medical journal. 2018;33(5):404-7. 16. ienghong k. factors affecting length of stay more than 4 hours in the emergency department of srinagarind hospital. srinagarind medical journal. 2014;29(1):7-13. 17. srisuk p, apiratwarakul k, ienghong k, rattanaseeha w, kotruchin p, buranasakda m. effectiveness of basic life support and automated external defibrillator shortcourse training in undergraduate students. srinagarind medical journal. 2017;32(4):332-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e39 or i g i n a l re s e a rc h clinical characteristics and associated factors of mortality in febrile neutropenia patients; a cross sectional study hamidreza hatamabadi1, ali arhami dolatabadi2, ayda akhavan2∗, saeed safari3 1. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, imam hossein hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2019; accepted: june 2019; published online: 27 july 2019 abstract: introduction: the duration and severity of neutropenia directly correlate with the incidence of life-threatening infections. this study aimed to evaluate the clinical characteristics and associated factors of mortality in febrile neutropenia patients. methods: this retrospective cross sectional study was conducted on all febrile neutropenia patients who were admitted to oncology department of two educational hospitals, tehran, iran, from 2011 to 2016. available patients’ data regarding baseline characteristics, treatment, and outcome were collected and analyzed using spss 21. results: 357 patients with the mean age of 50.9 ± 17.7 years were studied (59.7% female). mean white blood cell count of the studied patients was 715.1 ± 270.4 (100 – 1400) cells/mm3. the absolute neutrophil count (anc) of all patients was < 500 cells/mm3. the most frequent sources of malignancy in studied patients were gastrointestinal (35.9%), breast (22.4%), and sarcoma (15.7%), respectively. the mean time interval between initiation of treatment in ed and increase of anc to > 500 cells/mm3 was 2.45 ± 2.1 (1 – 16) days. 186 (52.1%) subjects reached anc > 500 cells/ mm3 after 2-5 days of hospitalization. the rate of hospital mortality was 5.3% (338 (94.7%) survived). the correlation between gender (p = 0.11), temperature (p = 0.123), number of ed visits (p = 0.765), presenting clinical manifestation (p = 0.201), source of malignancy (p = 0.328), presence of metastasis (p = 0.69), positive urine culture (p = 0.45), positive blood culture (p = 0.62), time from last chemotherapy (p = 0.677), and time to reach anc > 500 cells/mm3 (p = 0.739) with mortality was not significant. conclusion: based on the findings of the present study, the rate of hospital mortality in patients with febrile neutropenia was 5.3%. older age and lower white blood cell count were among the significant associated factors of mortality in this series. keywords: chemotherapy-induced febrile neutropenia; infection; mortality; risk factors cite this article as: hatamabadi h, arhami dolatabadi a, akhavan a, safari s. clinical characteristics and associated factors of mortality in febrile neutropenia patients; a cross sectional study. arch acad emerg med. 2019; 7(1): e39. 1. introduction the occurrence of fever in patients with cancer and reduced immune status is one of their subsequent problems. the lowest normal limit for circulating neutrophils is 1500 cells/mm3. the duration and severity of neutropenia directly correlate with the incidence of infections including those that are life-threatening. the incidence of infection finds a significant increase at the critical level of less than 500 cells/mm3 (1, 2). neutropenia can be acquired or inherited. ∗corresponding author: ayda akhavan; emergency department, imam hossein hospital, madani avenue, imam hossein square, tehran, iran. email: aydaakhavan@yahoo.com its acquired type is common and is associated with different malignant conditions, radiotherapy and chemotherapy, and also idiosyncratic response to drugs such as phenothiazines, sulfonamides, penicillins, cephalosporins, and vancomycin (3). neutropenia is the most prominent factor in the incidence of infection in patients undergoing chemotherapy or bone marrow transplantation, and fever is the most common symptom in these patients. about twenty years ago, gramnegative microorganisms were the most commonly isolated pathogens in patients with fever and neutropenia, but in recent years, gram-positive microorganisms have become more common and are found in about 60-50% of infections (4, 5). today, fever in patients with a reduced level of immunity has become a major problem in hospitals. due to the medical adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. hatamabadi et al. 2 vances in the use of immunosuppressive drugs for the transplantation of various organs, the number of patients with fever and neutropenia has increased significantly (6). those with persistent fever may be at risk for complications and need rapid medical treatment with antibiotics. individuals with anc > 500 cells/µl do not require treatment with granulocyte colony stimulating factor (g-csf), but do require close monitoring for inflammation (7, 8). the mortality rate of febrile neutropenia has been reported from 5.4% to 15% in different studies (9-11). patient characteristics, type of malignancy, age, race, prolonged neutropenia and infectious complications are stated as contributing factors of death in studies (12-14). we are faced with an increasing number of febrile neutropenia patients in our emergency departments and this study aimed to evaluate the clinical characteristics and associated factors of mortality in these patients. 2. methods 2.1. study design and setting this retrospective cross sectional study was conducted on all febrile neutropenia patients who were admitted to oncology departments of imam hossein and shohadaye tajrish hospitals, tehran, iran, from 2011 to 2016. available patients’ data regarding baseline characteristics, treatment, and outcome were collected and analyzed using spss 21. the study group adhered to the principles of medical ethics introduced by the ministry of health and the declaration of helsinki and legislation in the medical ethics committee of shahid beheshti university of medical sciences. in addition, the ethics committee of shahid beheshti university of medical sciences approved the protocol of the study (ethics code: ir.sbmu.msp.rec.1395.141). 2.2. participants data of all ≥ 15 years old febrile neutropenia patients who were admitted to the oncology departments of motioned hospitals were collected using census sampling method. subjects with incomplete medical records were excluded. 2.3. data gathering data were recorded using a predesigned checklist containing demographic variables (gender, age), malignancy type, clinical presentation, time from last chemotherapy, type of received antibiotics, blood culture, urinary culture, cell blood count, neutrophil count, presenting temperature, number of ed visits, as well as outcome (survival, death). a trained third year emergency medicine resident was responsible for data gathering under direct supervision of an emergency medicine specialist. 2.4. definitions one time oral temperature of 38.3◦ c (101◦ f) or a persistent oral temperature > 38.0◦ c (100.4◦ f) for > 1 hour was defined as fever and anc ≤ 500 cell/mm3 was defined as neutropenia in this study. 2.5. statistical analysis data were analyzed using spss version 21 and p<0.05 was considered significant. findings were presented as mean ± standard deviation or frequency and percentage. t-test was used for comparing quantitative variables and chi-square or fisher’s exact test for qualitative ones. 3. results 3.1. baseline characteristics of febrile neutropenia patients 357 patients with the mean age of 50.9 ± 17.7 (16 – 88) years were studied (59.7% female). mean temperature at the time of presentation to ed was 38.7 ± 0.4 (38.1 – 40) celsius. mean white blood cell count of the studied patients was 715.1 ± 270.4 (100 – 1400) cell/mm3. the anc of all patients was < 500 cell/mm3. table 1 shows the baseline characteristics of the studied patients. the most frequent sources of malignancy in the studied patients were gastrointestinal (35.9%), breast (22.4%), and sarcoma (15.7%), respectively. 327 (91.7) cases had visited ed for the first time and 262 (73.4%) cases had presented 6-10 days from last chemotherapy. 43 (12.0%) cases with positive blood culture and 18 (5.0%) cases with positive urine culture were detected. 3.2. outcome the mean time interval between initiation of treatment in ed and anc increasing to > 500 cells/mm3 was 2.45 ± 2.1 (1 – 16) days. 186 (52.1%) subjects reached anc > 500 cells/ mm3 after 2-5 days of hospitalization. the rate of hospital mortality was 5.3% (338 (94.7%) survived). table 3 compares different baseline characteristics of survived and non-survived subjects. the correlation between gender (p = 0.11), temperature (p = 0.123), number of ed visits (p = 0.765), presenting clinical manifestation (p = 0.201), source of malignancy (p= 0.328), presence of metastasis (p = 0.69), positive urine culture (p = 0.45), positive blood culture (p = 0.62), time from last chemotherapy (p = 0.677), and time to reach anc > 500 cell/mm3 (p = 0.739) with mortality was not significant. mean white blood cell count of survived and non-survived patients was 725.7 ± 268.7 and 526.3 ± 232.9 cell/mm3, respectively (p = 0.002). the mean age of those who survived was significantly lower (table 3; p = 0.005). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e39 table 1: baseline characteristics of studied patients variables number (%) gender male 144 (40.3) female 213 (59.7) age ( year) < 20 27 (7.5) 21-40 80 (22.4) 41-60 126 (35.3) > 61 124 (34.7) source of malignancy lung 20 (5.6) gastrointestinal 128 (35.9) breast 80 (22.4) sarcoma 56 (15.7) genitourinary 35 (8.8) gynecology 17 (4.8.2) endocrine 13 (5.1) blood 8 (2.2) clinical manifestations dyspnea 27 (7.5) vomiting 58 (16.2) diarrhea 122 (34.2) cough 17 (4.8) weakness 54 (5.1) urinary symptoms 10 (2.9) abdominal pain 24 (6.7) others 23 (6.4) time from last chemotherapy (day) 1-5 46 (12.9) 6-10 262 (73.4) > 11 49 (13.7) metastasis positive 93 (26) negative 264 (74) number of ed visits 1 327 (91.7) 2 22 (6.1) 3 5 (1.4) ≥4 3 (0.8) 4. discussion based on the findings of the present study, the rate of hospital mortality in patients with febrile neutropenia was 5.3%. older age and lower white blood cell count were among the significant associated factors of mortality in this series. there was not any significant relationship between mortality and gender, temperature, number of ed visit, clinical manifestation, source of malignancy, presence of metastasis, positive urine culture, positive blood culture, time from last chemotherapy, or time to reach anc > 500 cell/mm3. the mean age of patients in this study was 50.9 years and about 60% of cases were female. this finding is in line with amini et al. study, which reported the mean age and gender distribution of neutropenia fever patients as 46 years and 52%, respectively (15) and also fotokian et al. findings, which calcutable 2: cultures and antibiotic therapy variables number (%) antibiotics meropenem 201 (56.3) meropenem and vancomycin 85 (23.8) imipenem 45 (12.6) imipenem and vancomycin 5 (1.4) vancomycin 1 (0.2) tazocin 1 (0.2) ceftazidime 8 (2.2) others 11 (3.1) blood culture positive 43 (12.0) negative 314 (88.0) urine culture positive 18 (5.0) negative 339 (95.0) lated the mentioned measures as 43 years and 50%, respectively (16). the most common sources of malignancy were gastrointestinal and breast, respectively; and diarrhea and vomiting were among the most frequent symptoms of patients in this series. in the study by lakshmaiah et al. the most common sources of malignancy were lymphoma, leukemia, and germ cell tumors (17). in hosseini et al. study, the majority of patients had lymphatic cancers (18). hakim et al. reported bloodlymphatic cancers (16%) as the most common type of cancers, followed by solid tumors (19). tamai et al. reported blood cancers and respiratory symptoms as the most common source of malignancy and patients’ complaint, respectively, in their series (20). these differences among the studies regarding the source of malignancy may be due to different distribution of malignancy types among countries and regions. we observed that almost 50% of individuals reached anc > 500 cells/mm3 after 2-5 days of treatment. consistent with our finding, cortes el al. revealed that the anc of 56% of cases had improved and reached more than 500 cells/mm3 after four days (21). another study showed that more than 80% of patients improve after a course of treatment (22). in this study, we observed that antibiotic type did not significantly influence patient outcome. malik et al. found that use of the combination of ceftazidime and amikacin did not have any advantages over ceftriaxone monotherapy (23). these findings are also consistent with the results of the studies by walsh et al., ben et al., and malik et al., because they concluded that single-agent regimens of ceftazidime and imipenem were equally effective in controlling neutropenic fever in patients with cancer (23-25). in our study, 11.2% and 3.9% of patients had positive blood and urine cultures, respectively. in many studies, bacteremia was reported in about 100% of patients (26, 27). in hosseini’s study, 13.7% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. hatamabadi et al. 4 table 3: comparison of different variables between survived and non-survived patients variables survived p value yes (n = 338) no (n = 19) gender male 136 (97.7) 5 (2.3) 0.11 female 208 (94.4) 8 (5.6) age ( year) mean ± sd 50.3 ± 17.6 62.1 ± 12.7 0.005 temperature mean ± sd 38.7 ± 0.4 38.5 ± 0.2 0.123 metastasis positive 89 (95.7) 4 (4.3) 0.69 negative 255 (96.6) 9 (3.4) urine culture positive 14 (100) 0 (0) 0.45 negative 330 (96.2) 13 (3.8) blood culture positive 38 (95) 2 (5) 0.62 negative 306 (96.5) 11 (3.5) wbc count (cell/mm3 ) mean ± sd 725.7 ± 268.7 526.3 ± 232.9 0.002 time to anc>500 cell/mm3 (days) mean ± sd 2.4 ± 2.1 2.7 ± 1.2 0.736 time from last chemotherapy (days) mean ± sd 7.8 ± 2.7 8.1 ± 4.0 0.677 data are presented as mean ± standard deviation (sd) or number (%). wbc: white blood cell; anc: absolute neutrophil count. of patients had a positive blood culture, and 13.7% had positive urine culture (18). in soroush et al. study, the prevalence of positive blood culture and urine culture was 8% and 5%, respectively (28). in a study on mortality of cancer patients with febrile neutropenia, gray et al. concluded that adjusted risk of mortality increased 15% in cases experiencing febrile neutropenia (9). chen et al., reported the death rate of neutropenia fever patients as 5.7% (10). furthermore, ahn et al. reported that 5.4% of patients admitted to hospital with neutropenia fever died (11). patient characteristics, type of malignancy, comorbidities, and infectious complications were among the most important associated factors of mortality in adult cancer patients with febrile neutropenia in one study (12). in the study by swati et al. race, age, year of discharge, associated complications, and cancer type were significantly associated with higher mortality of these patients (13). in another study prolonged neutropenia, acute renal failure, nosocomial bacteremia, age > 55 years, and monomicrobial bacteremia were among the significant predictive factors of mortality in hematologic patients with bacteremia (14). it is clear that the risk factors of mortality in febrile neutropenia are different among studies. this could be due to different economic, social, health, and case mix of these studies. it seems that each country or even each hospital should try to explore their own contributing factors of mortality and plan to reduce its rate via controlling the modifiable factors. 5. limitation it should be noted that in the current study due to lack of access to patients, it was not possible to find other infectious sites. 6. conclusion based on findings of the present study, the rate of hospital mortality in patients with febrile neutropenia was 5.3%. older age and lower white blood cell count were among the significant associated factors of mortality in this series. 7. appendix 7.1. acknowledgements this study is derived from dr. aida akhavan’s thesis for achieving her specialist degree in emergency medicine. 7.2. author contribution the author met the standard criteria for authorship based on the recommendations of the international committee of medical journal editors. authors orcids hamidreza hatamabadi: 0000-0002-9085-8806 ali arhami dolatabadi: 0000-0001-9492-9520 saeed safari: 0000-0002-7407-1739 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e39 7.3. funding/support no funding to declare. 7.4. conflict of interest the authors declared no competing interests. references 1. lehrnbecher t, phillips r, alexander s, alvaro f, carlesse f, fisher b, et al. guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. journal of clinical oncology. 2012;30(35):4427-38. 2. santolaya m, alvarez a, acuna m, aviles c, salgado c, tordecilla j, et al. efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial. clinical microbiology and infection. 2017;23(3):173-8. 3. el haddad h, chaftari a-m, hachem r, micheal m, jiang y, yousif a, et al. procalcitonin guiding antimicrobial therapy duration in febrile cancer patients with documented infection or neutropenia. scientific reports. 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reynolds mw, barron r, tomic ks, yu j. risk of mortality in patients with cancer who experience febrile neutropenia. cancer. 2010;116(23):555563. 10. chen y, wang y, shi y, dai g. timing of chemotherapyinduced neutropenia predicts prognosis in metastatic colon cancer patients: a retrospective study in mfolfox6-treated patients. bmc cancer. 2017;17(1):242. 11. ahn s, lee y-s. predictive factors for poor prognosis febrile neutropenia. current opinion in oncology. 2012;24(4):376-80. 12. kuderer nm, dale dc, crawford j, cosler le, lyman gh. mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. cancer. 2006;106(10):2258-66. 13. basu sk, fernandez id, fisher sg, asselin bl, lyman gh. length of stay and mortality associated with febrile neutropenia among children with cancer. journal of clinical oncology. 2005;23(31):7958-66. 14. tumbarello m, spanu t, caira m, trecarichi em, laurenti l, montuori e, et al. factors associated with mortality in bacteremic patients with hematologic malignancies. diagnostic microbiology and infectious disease. 2009;64(3):320-6. 15. adnan a. evaluation of the results of body fluid production in patients with fever and neutropenia from 2000 to 2005 in sina hospital, hamedan. journal of hamadan university of medical sciences. 2005;3(2):12-20. 16. fotoukian z, keyhanian s, ghafari f, khabiri n, saravi m. comparison the efficacy of ceftazidime and imipenem in treatment of neutropenic febrile due to chemotherapy in cancer patientsv. 2009. 17. lakshmaiah kc, malabagi as, govindbabu rs, sinha m, jayashree rs. febrile neutropenia in hematological malignancies: clinical and microbiological profile and outcome in high risk patients. journal of laboratory physicians. 2015;7(2):116. 18. hosseini m. frequency and causes of fever in patients admitted with fever and neutropenia. journal of ilam university of medical sciences. 2004;1(4):12-8. 19. hakim h, flynn pm, knapp km, srivastava dk, gaur a. etiology and clinical course of febrile neutropenia in children with cancer. journal of pediatric hematology/oncology. 2009;31(9):623. 20. tamai y, imataki o, kawakami k. fever profile of febrile neutropenia in patients treated with cancer chemotherapy for hematological malignancies. gan to kagaku ryoho cancer & chemotherapy. 2010;37(5):859-62. 21. cortes ja, cuervo s, gomez ca, bermudez d, martinez t, arroyo pjb. febrile neutropenia in the tropics: a description of clinical and microbiological findings and their impact on inappropriate therapy currently used at an oncological reference center in colombia. 2013;33(1):70-7. 22. stern a, carrara e, bitterman r, yahav d, leibovici l, paul mjcdosr. early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. 2019(1). 23. malik i. comparison of meropenem with ceftazidime as monotherapy of cancer patients with chemotherapy inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. hatamabadi et al. 6 duced febrile neutropenia. journal-pakistan medical association. 2002;52(1):15-7. 24. rolston kv, berkey p, bodey gp, anaissie ej, khardori nm, joshi jh, et al. a comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. archives of internal medicine. 1992;152(2):283-91. 25. meropenem study group of leuven l, nijmegen. equivalent efficacies of meropenem and ceftazidime as empirical monotherapy of febrile neutropenic patients. journal of antimicrobial chemotherapy. 1995;36(1):185-200. 26. gencer s, salepci t, ozer s. evaluation of infectious etiology and prognostic risk factors of febrile episodes in neutropenic cancer patients. journal of infection. 2003;47(1):65-72. 27. el-mahallawy h, sidhom i, el-din na, zamzam m, ellamie m. clinical and microbiologic determinants of serious bloodstream infections in egyptian pediatric cancer patients: a one-year study. international journal of infectious diseases. 2005;9(1):43-51. 28. soroush j, razavi s, nojoomi m. comparing two empiric antibiotic regimens in treatment of febrile neutropenic cancer patients. razi journal of medical sciences. 2003;10(36):547-52. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem archives of academic emergency medicine. 2020; 8(1):e27 rev i ew art i c l e intravenous amide anesthetics to treat pain associated with renal colic in the emergency department: a systematic review andrew c. miller1,2∗, colton faza1, alberto a. castro bigalli3, abbas m. khan2, kerry a. sewell4, alexandra king5, amir vahedian-azimi6, shahriar zehtabchi7 1. department of emergency medicine, vidant medical center, east carolina university brody school of medicine, greenville, nc, usa. 2. the morzak collaborative, greenville, nc, usa. 3. east carolina university brody school of medicine, greenville, nc, usa. 4. william e. laupus health sciences library, east carolina university, greenville, nc, usa. 5. emergency medicine and toxicology department, vidant medical center, greenville, nc, usa. 6. trauma research center, nursing faculty, baqiyatallah university of medical sciences, tehran, iran 7. department of emergency medicine, state university of new york (suny) downstate medical center, brooklyn, ny, usa. received: january 2020; accepted: february 2020; published online: 18 march 2020 abstract: introduction: renal colic affects 12% of the u.s. population, accounting for nearly 1% of emergency department (ed) visits. current recommendations advocate narcotic-limiting multimodal analgesia regimens. the objective of this review is to determine if in patients with renal colic (population), intravenous (iv ) amide anesthetics (intervention) result in better pain control, lower requirements for rescue analgesia, or less adverse medication effects (outcome) compared to placebo, non-steroidal anti-inflammatory drugs (nsaids), or opiates (comparisons). methods: scholarly databases and relevant bibliographies were searched using a pre-designed systematic review protocol and registered with prospero. inclusion criteria were: (1) randomized clinical trial (rct), (2) age ≥ 18 years, (3) confirmed or presumed renal colic, (4) amide anesthetic administered iv. eligible comparison groups included: placebo, conventional therapy, acetaminophen, nsaid, or opiate. the primary outcome was pain intensity at baseline, 30, 60, and 120 minutes. trial quality was graded, and risk-of-bias was assessed. results: of the 3930 identified references, 4 rcts (479 participants) were included. one trial (n=240) reported improved analgesia with iv lidocaine (lidoiv ) plus metoclopramide, compared to morphine. all other trials reported unchanged or less analgesia compared to placebo, ketorolac, or fentanyl. very severe heterogeneity (i2= 88%) precluded pooling data. conclusion: current evidence precludes drawing a firm conclusion on the efficacy or superiority of lidoiv over traditional therapies for ed patients with renal colic. evidence suggests lidoiv may be an effective non-opiate analgesic alliterative; however, it’s efficacy may not exceed that of nsaids or opiates. further study is needed to validate the potential improved efficacy of lidoiv plus metoclopramide. keywords: renal colic; kidney calculi; lidocaine; analgesia; emergency service, hospital cite this article as: c. miller a, faza c, a. castro bigalli a, m. khan a, a. sewell k, king a, vahedian-azimi a, zehtabchi sh. intravenous amide anesthetics to treat pain associated with renal colic in the emergency department: a systematic review. arch acad emerg mede. 2020; 8(1): e27. ∗corresponding author: dr. andrew c. miller; department of emergency medicine east carolina university, brody school of medicine, 600 moye blvd, mailstop 625, greenville, nc 27834, phone: +1 (252) 744-5726, fax: +1 (252) 744-5014, e-mail: taqwa1@gmail.com, e-mail: millerandr17@ecu.edu. 1. introduction pain is the most common reason for emergency department (ed) visits in the united states (u.s.) (1), and its management requires mastery of multimodal approaches to achieve safe and effective analgesia. nephrolithiasis and renal colic affect approximately 12% of the u.s. population (up to 5% in china) (2) and accounts for nearly 1% of ed visits and hospital adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. c. miller et al. 2 missions in the u.s. (2–5). for patients with prior stones, 10-year recurrence rates approach 50% (3,6). the pain of renal colic origin is multifactorial and is related to obstruction of urinary flow with subsequent increase in prostaglandinmediate ureteral spasm (6,7). as most renal calculi pass spontaneously, acute management should focus on rapid analgesia, diagnosis confirmation, and recognition of complications requiring immediate intervention (7). approximately 85% of ed patients with renal colic are treated with analgesics (3). whether used alone or in combination, nsaids and opioids constitute the primary therapeutic medications in ed management of renal colic (8). each drug class possesses potentially unfavorable side effects and contraindications. disadvantages to nsaids include lack of titratability, nausea, epigastric pain, and contraindications including renal insufficiency, peptic ulcer disease, the elderly (age >70 years), and concomitant use of anticoagulation or antiplatelet agents (9). opioid administration in turn may lead to nausea, vomiting, pruritus, lethargy, bradycardia, hypotension, or respiratory depression, and may be relatively contraindicated for patients with a history of opioid abuse or dependence. despite efficacy and possibly favorable side-effect profile of nsaids over opiates (6), 43% of patients are treated with an opiate, and 70% are prescribed an opiate on discharge (3). moreover, ed opioid administration and prescription has been linked to an increased risk of recurrent opioid use (10). current practice is moving towards recent u.s. food and drug administration (fda) goals that emphasize analgesia through multimodal regimens that decrease opiate use (11). insufficient data regarding the efficacy of alternative regimens and their side-effect profiles have hampered efforts to move away from opiate heavy regimens (12). there is a need for identification and validation of safe and effective analgesia techniques for renal colic, which limit narcotic consumption and prescription, and provide treatment alternatives for patients who are unable to tolerate or have serious contraindications to nsaids or opiates (12). intravenous local anesthetic use has emerged as an opiatesparing alternative in treatment of renal colic. local anesthetics halt impulse initiation and transmission processes in neuronal axons, and may be categorized into two major chemical classes: amino esters and amino amides (6). amide local anesthetics are widely used for topical and local anesthesia, and as systemic antiarrhythmics (1). lidocaine, an amino amide, has been described to have analgesic, antihyperalgesic, anti-inflammatory, and anti-bacterial properties (1,13,14). the analgesic effect from systemic administration affects both the peripheral and central nervous system (15). lidocaine decreases excitability and conduction of unmyelinated c fibers, and intravenous lidocaine (lidoiv ) suppresses post-synaptic reflexes in the spinal dorsal horn (15). its mechanisms include reversible inhibition of voltage-gated open and inactivated sodium channels and g-protein-coupled receptors (3,13,15,16). central antinociceptive effects are mediated through actions on muscarinic and nicotinic receptors, which in turn increase intraspinal acetylcholine release to reinforce the inhibitory descending pain pathway (15). anti-hyperalgesic effects are mediated through the n-methyl-d-aspartate (nmda) receptor (14,15). lidoiv has a desirable pharmacokinetic profile, with a rapid onset and long duration-of-action (half-life 60-120 min), but the analgesic effects may last longer (1,17). approximately, 90% of lidocaine is metabolized in the liver by dealkylation to lower potency active metabolites monoethylglycinexylidide (megx) and glycinexylidide (gx) (13,15), while ≤10% is excreted unchanged in the urine (15). lidoiv application for ed patients with renal colic has been reported to improve pain intensity, time to pain relief, and nausea in randomized clinical studies (8,18–21), nonrandomized clinical studies (22), and case series (17,23–25), and may be considered as a viable non-opioid addition or an alternative to traditional treatment modalities. we investigated the evidence on using intravenous amide anesthetics for analgesia and opioid sparing effects in patients with acute renal colic. the objective of this project is to address the following research question: in patients with renal colic (population) do intravenous amide anesthetics such as lidocaine (intervention) improve pain intensity, need for rescue analgesia, opiate consumption, or adverse events (outcomes) compared to placebo, nsaids, or opiates (comparisons)? 2. methods this systematic review followed the steps outlined in preferred reporting items for systematic reviews and meta-analyses (prisma) (26). a systematic protocol was developed a priori and registered with prospero (# crd42019130355). the primary outcome was pain intensity at baseline and 15, 30, 60, and 120 minutes post-treatment. the secondary outcomes were: (1) need for rescue analgesia at 30 or 60 minutes, (2) time to pain free, (3) treatment failure, and (4) adverse events. a librarian-performed systematic search strategy was conducted (supplemental digital content 1) in cochrane central, cinahl, embase, latin american and caribbean health sciences literature (lilacs), medline, scopus, and web of science (wos). additional investigatorperformed structured searches were conducted in: china national knowledge infrastructure (chkd-cnki), information/chinese scientific journals database (csjd-vip), directory of open access journals (doaj), ieee-xplorer, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1):e27 magiran, scientific information database (sid), tubitak ulakbim, russian science citation index (rsci), korean journal database (kci), and scientific electronic library online (scielo). relevant bibliographies were searched. searches were not limited by date, language, or publication status. clinical trial registries were searched to limit publication bias, including: clinicaltrials.gov, world health organization international clinical trials registry platform (who ictrp), and the australian new zealand clinical trials registry (anzctr). abstracts of the conference proceedings of the relevant disciplines (emergency medicine, urology, nephrology, pain management) were searched (past 5 years). when the presented data were incomplete, the authors were contacted to obtain the missing information. these trials were only included if the authors responded to correspondence affirmatively with the requested information. inclusion criteria were: (1) randomized controlled human clinical trial, (2) patients aged ≥ 18 years, (3) presumed or confirmed renal colic, (4) amino amide anesthetic administered intravenously (eg. lidoiv ) compared to placebo or another analgesic. data of pain intensity that measured as either a 10 cm visual analogue scale (vas) or 10-point numeric rating scale (nrs) were summarized. significant improvement in pain intensity was defined as improvement in ≥ 3 cm or points on vas or nrs, respectively. rescue analgesia was defined as any analgesia medication administered following the study drug. exclusion criteria were: (1) non-randomized study design, (2) studies enrolling patients aged < 18 years, (3) drug administration by routes other than intravenous, (4) studies published only in abstract form (or unpublished) for which the authors did not respond to correspondence by providing the requested information. reference management and application of inclusion/exclusion criteria was performed using covidence (covidence, melbourne, australia). four authors reviewed the titles and abstracts to determine inclusion eligibility. four authors extracted study data. any disagreements were resolved by consensus. four authors independently assessed the risk-of-bias (rob) using two validated tools: (1) grading of recommendations, assessment, development and evaluations (grade) (27), and rob 2.0: "revised tool for risk of bias in randomized trials" (28). the authors considered methods of randomization and allocation, blinding (of treatment administrator, participants, and outcome assessors), selective outcome reporting (e.g. failure to report adverse events), incomplete outcome data, and sample size calculation. each trial was graded as high, low or unclear risk of bias (rob) for each criterion. publication bias was assessed using both the egger (29) and begg-mazumdar methods (30). heterogeneity was evaluated using i2 statistic. the confidence interval for i2 was constructed using the iterative non-central chi-square distribution method of hedges and piggott (31). the threshold value for severe heterogenity was specified to be i2 ≥50%, and very serious heterogenity was specified as i2 >75%. data pooling and meta-analysis was planned if i2 <50%. 3. results the complete search was performed on december 19, 2018. the search strategy identified 3930 references, of which 4 rcts (479 participants) met the inclusion criteria (8,18–20). two ongoing studies were identified in clinical trial registries (32,33). see figure 1 for the prisma flow diagram. the included studies are summarized in table 1. one study took place in a high-income economy (usa) (8). three were in a middle-income economy (iran) (18–20). no studies were identified in low-income economies. two published abstracts were excluded. the first was an rct published only in abstract form for which the authors did not respond to correspondence (21). the second duplicated information available in a published manuscript (22). the primary reason for exclusion of full-text manuscripts was non-randomized study design. two unpublished ongoing trials were identified (32,33). no additional studies were identified through bibliographic and conference abstracts analyses that were not previously identified through other search methods. the grade assessments are presented in table 2. rob assessment indicated that how each study ranked regarding the risk of selection bias, performance bias, detection bias, reporting bias, and "other" bias (8,18–20). two studies were similarly at low risk for attrition bias (8,18), whereas 2 had unclear risk of attrition bias (19,20). lastly, 3 studies had low risk of bias due to sample size (8,19,20), whereas one had unclear rob (18). additionally, all of the included studies were double-blind (8,18–20). although all 4 studies had a control arm, but only one had a placebo arm (lidocaine + morphine vs. placebo + morphine) (18). one study reported no patient attrition (8), whereas one reported 19% attrition (18), and two did not report attrition data (19,20). furthermore, each included study reported their intended primary outcomes. moreover, one study reported adverse events (ae) (20), 2 reported no aes (8,18), and one did not report on aes (19). all but one study reported the method of sample size calculation (18). all included studies gave adequate information regarding diagnostic criteria, namely that patients were diagnosed with presumed or confirmed renal colic (8,18–20). heterogeneity was noted in the methods and timing of pain intensity assessments. three studies utilized a 10 cm vas scale (18–20), and 1 utilized a 10-point nrs (8). pain intensity was assessed at 15 minutes in 3 studies (8,19,20), at 30 minutes in 4 studies (8,18–20), at 60 minutes in 3 studies (8,18,20), and at 120 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. c. miller et al. 4 table 1: list of included studies author [ year]; (reference #) setting, design (n) intervention comparison demographics: lidocaine (l) vs. no lidocaine (nl) primary endpoints secondary endpoints firouzian [2016]; (18) iran, single center, rct, doubleblind (89) lidocaine 1.5 mg/kg iv plus morphine 0.1 mg/kg infusion over 2-4 minutes. morphine 0.1 mg/kg plus n.s. bolus infusion over 2-4 minutes. age, years: (l) 37.91±10.76, (nl) 37.95±12.6 sex, male: (l) 77%, (nl) 83% pain intensity measured by vas (0-10) at baseline, 5, 10, 30, 60, and 120 minutes. (1) time to pain free (2) nausea intensity (3) time to nausea free motamed [2017]; (19) iran, single center, rct, doubleblind (90) lidocaine 1.5 mg/kg iv infusion over 2 minutes. fentanyl 1.5 mcg/kg iv infusion over 2 minutes. age, years: (l) 39.08±6.64, (nl) 34.08±8.87 sex, male: (l) 86.7%, (nl) 93.3% pain intensity measured by vas (0-10) at baseline, 5, 10, 15, and 30 minutes. rescue medication at 15& 30-minutes postadministration. motov [2019]; (8) usa, single center, rct, doubleblind (150) lidocaine 1.5 mg/kg iv infusion over 10 minutes. (1) ketorolac 30 mg iv push with 10 min n.s. infusion. (2) ketorolac 30 mg iv push plus lidocaine 1.5 mg/kg iv infusion over 10 minutes. age, years: (l only) 39.34±10.95 (combination) 42.92±10.36 (nl) 42.34±10.47 sex, male: (l only) 54%, (combination) 56%, (nl) 56% pain intensity measured by numerical rating scale (0-10) at baseline, 5, 10, 30, and 60 minutes. (1) adverse effects (2) use of diagnostic imaging soleimanpour [2012]; (20) iran, single center, rct, doubleblind, (150) lidocaine 1.5 mg/kg iv slow push from 10 cc syringe. morphine 0.1 mg/kg iv slow push from 10 cc syringe. age, years: (l) 37.71±11.08, (nl) 35.23±12.37 sex, male: (l) 28%, (nl) 72% pain intensity measured by vas (0-10) at baseline, 5, 10, 15, and 30 minutes. (1) pain resolution measured as vas < 3/10 for 30 minutes. (2) rescue medication at 30 minutes. (3) adverse effects abbreviations: ed means emergency department; iv means intravenous; n.s. means normal saline; rct means randomized controlled trial; vas means visual analogue scale. table 2: grade quality of evidence ratings certainty assessment variable no of studies study design risk of bias inconsistency indirectness imprecision other considerations certainty pain intensity 4 rct not serious serious not serious not serious none ⊕⊕⊕©moderate rescue medication 1 rct not serious not serious not serious not serious publication bias strongly suspected ⊕⊕⊕©moderate time to pain free 1 rct not serious not serious not serious not serious publication bias strongly suspected ⊕⊕⊕©moderate treatment failure 1 rct not serious not serious not serious not serious publication bias strongly suspected ⊕⊕⊕© moderate rct means randomized controlled trial. minutes in 2 studies (8,18). only one study assessed time to pain-free (18), one assessed treatment failure (19), and one assessed the need for rescue analgesia (at 30 and 60 minutes) (8). all four included trials gave adequate statistical descriptions; including appropriate use of statistical tests (8,18–20). no significant baseline differences were noted between groups (8,18–20). with the exception of one trial that reported better pain control with lidocaine (compared to iv morphine) at 10, 15, and 30 minutes post-administration (20), all other trials reported similar (or worse) pain intensity compared to placebo (18), ketorolac (8), or fentanyl (figure 3) (19). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1):e27 figure 1: prisma flow diagram. since not all trials reported immediate (10 minutes postadministration) or longer pain relief (60 or 120 minutes postadministration), it was not possible to draw a conclusion about the immediate or long-term analgesia effects of lidoiv. a forest plot depicting pain score comparisons between regimens with and without lidocaine is provided in figure 2. neither the egger (z = 1.31, p-value = 0.1892) nor beggmazumdar method (z = -0.89, p-value = 0.6273) identified evidence of publication bias (figure 3). the planned metaanalysis was not performed due to very severe heterogeneity (i2 >75%). 4. discussion this project aimed to clarify the clinical efficacy of lidoiv for decreasing the pain intensity and analgesic requirements associated with acute renal colic. although substantial improvement was not noted over comparators, overall, some observations warrant further discussion. of note, the methodology of the soleimanpour et al. study that did report improvement over morphine differed from the other studies in a few important ways, namely: (1) coadministration with metoclopramide and (2) conservative iv fluid strategy (20). metoclopramide is a procaine amide structural analogue that may exert both antiemetic and analgesic effects. proposed mechanisms include calcium channel-, opiate-, and prolactin-mediated mechanisms. the latter contributes to the analgesic action of the endogenous opioid system as evidenced by its reversibility by naloxone. additionally, metoclopramide is a dopamine antagonist, increasing acetylcholine levels at neuro-effector junctions and postganglionic nerve terminals by inhibiting the action of acetylcholinesterase. metoclopramide has been described to have antispasmodic effects on ureteral smooth muscle (34). studies have described its analgesic efficacy in acute renal colic to exceed those of the isosorbide dinitrate (35), morphatropin (36), tenoxicam (37), and xintonding (38); however, findings were not significant for metoclopramide plus dipyrone vs. ketorolac alone (39), or metoclopramide plus pethidine vs. morphine alone (40). it has been described that combining lidocaine with metoclopramide may increase analgesia over lidocaine alone (41). it remains unclear whether an analgesia augmenting synergistic relationship exists between metoclopramide and the amide anesthetics. the second way in which the study by soleimanpour et al. differed from the others was fluid management strategy. in many regions, it is commonplace to treat patients with acute renal colic with forced iv fluids; however, this remains controversial. large volumes of iv fluids are often administered to produce a diuresis that mechanically "flushes out" the stone. however, the benefit of this approach has not consistently borne out in clinical practice (42,43). the soleimanpour et al. protocol did not administer forced iv fluids (20), whereas the other included studies did not specify the iv fluid management stratthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. c. miller et al. 6 figure 2: forrest plot of pain scores in lidocaine-containing versus no lidocaine regimens. egy (8,18,19). the influence of varied hydration strategies on the outcomes of these studies remains unclear. in some situations, lidoiv doses may need to be modified. with commonly recommended doses, lidocain’s therapeutic index remains very high and plasma concentrations stay largely below the cardiotoxic and neurotoxic threshold levels (15). for renal colic, the recommended dose of lidoiv is 1.5 mg/kg (maximum 200 mg/dose) administered over 2030 minutes (17,23,25). for patients being admitted, repeat dosing or an infusion may be used to maintain a steadystate plasma concentration: 1.5 mg/kg iv bolus, then 50 µg/kg/min (3.0 mg/kg) iv infusion for one hour, then 25 µg/kg/min (1.5 mg/kg) iv infusion for the second hour (h), then 12 µg/kg/min (0.7 mg/kg) iv infusion for the next 22 h, and finally 10 µg/kg/min (0.6 mg/kg) iv infusion from 24 to 48 h (15). without a loading dose, it takes >60 min for lidoiv to achieve a therapeutic steady-state plasma concentration (15). although continuous lidocaine infusion might theoretically lead to toxicity over time, blood concentrations reported in clinical studies have remained below toxic levels ( 5 µg/ml), except for cardiac surgery trials in which higher doses were used for longer durations (15). as hepatic blood flow appears to be a limiting factor for lidocaine metabolism (13), the reduction in hepatic blood flow in patients with congestive heart failure may prolong the elimination half-life (t1/2) (44). no dose adjustment is necessary in patients with moderate liver cirrhosis; however, the dose should be decreased by 50% in patients with severe cirrhosis (child score c) (45). additionally, firstand second-degree heart blocks could be exacerbated and progress to a higher degree block with lidocaine administration, and both cardiovascular instability and concomitant use of alpha-agonists or beta-blockers are relative contraindications (46). moreover, lidocaine clearance is linearly altered with kidney impairment, thus the elimination t1/2 of lidocaine and gx (but not megx) is doubled in case of severe renal insufficiency (47). volume of distribution is also an important factor when considering lidoiv dose and metabolism. elderly patients have an increase in apparent volume of distribution, and consequently a significantly longer elimination t1/2 compared to younger patients (2.7 vs. 1.6 h) (48). for elderly patients, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1):e27 figure 3: funnell plot and publication bias assessment. the initial loading dose should be the same, but any continuous infusion rate should be decreased by approximately 35% (15). the increased volume of distribution similarly accounts for the prolonged clearance seen in obese patients compared to non-obese patients (48). for obese patients, the bolus or loading dose should be calculated based on the patient’s total body weight, but the continuous infusion rate should be based on the ideal body weight (15). lastly, lidocaine crosses the placenta and the blood–brain barriers via simple passive diffusion, and is excreted in breast milk (15). thus, the clearance rate should be taken into consideration for breastfeeding mothers to avoid toxicity in the breast-fed infant (15). 5. limitations since the data from some studies was unavailable, some risk of publication and selective reporting bias exists. additionally, all included studies were conducted in asia and north america. it is possible that genetic differences in drug metabolism or response may account for some of the observed variation in response. we identified no other systematic reviews or meta-analyses on this topic for comparison. 6. conclusion while we cannot draw a firm conclusion on the efficacy or superiority of intravenous lidocaine over traditional therapy for the treatment of renal colic in the emergency department, the available evidence indicates that the analgesic effects of intravenous lidocaine may not exceed that of nsaids or opiates. although evidence exists to suggest the efficacy of intravenous lidocaine as an alternative treatment modality for acute renal colic, additional study is needed to clarify its role as compared to other traditional treatment modalities. 7. declaration 7.1. acknowledgements we thank dr. seyed m. hosseininejad from mazandaran university of medical sciences (sari, iran) (18), dr. hassan soleimanpour from tabriz university of medical sciences (tabriz, iran) (20), and dr. mohammadreza maleki verki from ahvaz jundishapur university of medical sciences (ahvaz, iran) (19) for supplying unpublished summary data from their respective studies (18). we also thank mr. jefferson drapkin from maimonides medical center in brooklyn, ny, usa for responding to inquiries for data clarification (8). the authors attest to the originality of this previously unpublished work, that all listed authors contributed meet international committee of medical journal editors (icmje) criteria for authorship, and that all persons meeting icmje authorship criteria are credited. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. c. miller et al. 8 7.2. authors contributions concept generation and project supervision was performed by acm. literature searches were performed by acm and kas. studies were screened for inclusion by acm, cf, aacb and amk. data was abstracted by acm, cf, aacb and amk. unpublished data was acquired from corresponding authors by acm, ava and sz. risk-of-bias analysis and evidence grading was performed by acm, cf, aacb and amk. statistics and figure generation was performed by acm, ava and sz. manuscript preparation was performed by acm, cf, aacb, amk, ava and sz. manuscript revision was performed by acm and sz. authors orcids andrew c. miller: 0000-0001-8474-5090 colton faza: 0000-0002-0287-2801 alberto a. castro bigali: 0000-0002-1813-3333 abbas m. khan: 0000-0001-6295-3788 kerry sewell: 0000-0002-0405-3789 alexandra r. king: 0000-0002-6123-2943 amir vahedian-azimi: 0000-0002-1678-7608 shahriar zehtabchi: 0000-0002-6427-986x 7.3. funding support no funding was received for this work. 7.4. conflict of interest the authors have no conflicts of interest to disclose. there were no sources of funding or support for this project. 7.5. differences between protocol and review due to significant methodological heterogeneity between studies, the planned meta-analysis was not performed. references 1. e silva loj, scherber k, cabrera d, motov s, erwin pj, west cp, et al. safety and efficacy of intravenous lidocaine for pain management in the emergency department: a systematic review. ann emerg med. 2018 aug; 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[spanish]. 40. o’connor a, schug sa, cardwell h. a comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. j accid emerg med. 2000; 17 (4):261–4. 41. safavi m, honarmand a, yazdanpanah a. adding metoclopramide to lidocaine for intravenous regional anesthesia in trauma patients. adv biomed res. 2014; 3:45. 42. worster as, bhanich supapol w. fluids and diuretics for acute ureteric colic. cochrane database syst rev. 2012; 2:cd004926. 43. springhart wp, marguet cg, sur rl, norris rd, delvecchio fc, young md, et al. forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial. j endourol. 2006; 20 (10):713–6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. c. miller et al. 10 44. nation rl, triggs ej, selig m. lignocaine kinetics in cardiac patients and aged subjects. br j clin pharmacol. 1977; 4 (4):439–48. 45. orlando r, piccoli p, de martin s, padrini r, palatini p. effect of the cyp3a4 inhibitor erythromycin on the pharmacokinetics of lignocaine and its pharmacologically active metabolites in subjects with normal and impaired liver function. br j clin pharmacol. 2003; 55 (1):86–93. 46. pasero c. intravenous lidocaine for acute pain treatment. j perianesthesia nurs. 2011; 26 (3):166–9. 47. de martin s, orlando r, bertoli m, pegoraro p, palatini p. differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis. clin pharmacol ther. 2006; 80 (6):597–606. 48. abernethy dr, greenblatt dj. lidocaine disposition in obesity. am j cardiol. 1984; 53 (8):1183–6. supplemental digital content 1; literature search strategy medline via pubmed ("renal colic"[mesh] or "kidney calculi"[mesh] or "colic"[mesh] or "nephrolithiasis"[mesh:noexp] or "urinary calculi"[mesh] or ((renal[tiab] or kidney[tiab] or ureteral[tiab] or ureteric[tiab] or urinary[tiab]) and (colic[tiab] or colics[tiab] or pain[tiab] or stone[tiab] or stones[tiab] or calculus[tiab] or calculi[tiab])) or urolithiasis[tiab] or nephrolithiasis[tiab] or "tract stone"[tiab] or "tract stones"[tiab] or "acute pain"[tiab] or "abdominal pain"[tiab] or "abdominal cramps"[tiab] or "abdominal cramping"[tiab]) and (lidocaine[mesh] or lignocaine[tiab] or xylocaine[tiab] or lidocaine[tiab] or lignocain[tiab] or xylocain[tiab] or xyloneural[tiab] or octocaine[tiab] or xylocitin[tiab]) and (randomized controlled trial[pt] or controlled clinical trial[pt] or randomized[tiab] or placebo[tiab] or drug therapy[sh] or randomly[tiab] or trial[tiab] or groups[tiab]) not ((animals [mh] not humans [mh])) or articaine or (mepivacaine and intravenous and renal) or (rrilocaine and intravenous and renal) or (ropivacaine and intravenous and renal) or (cinchocaine and intravenous) or (etidocaine and intravenous) embase: (’kidney colic’/exp or ’colic’/exp or ’urolithiasis’/exp or ’ureter obstruction’/exp or ((renal:ab,ti or kidney:ab,ti or ureteral:ab,ti or ureteric:ab,ti or urinary:ab,ti) and (colic:ab,ti or colics:ab,ti or pain:ab,ti or stone:ab,ti or stones:ab,ti or calculus:ab,ti or calculi:ab,ti)) or nephrolithiasis:ab,ti or urolithiasis:ab,ti or "tract stone":ab,ti or "tract stones":ab,ti or "acute pain":ab,ti or "abdominal pain":ab,ti or "abdominal cramps":ab,ti or "abdominal cramping":ab,ti) and (’lidocaine’/exp or lignocaine:ab,ti or xylocaine:ab,ti or lidocaine:ab,ti or lignocain:ab,ti or xylocain:ab,ti or xyloneural:ab,ti or octocaine:ab,ti or xylocitin:ab,ti) and (’crossover procedure’:de or ’double-blind procedure’:de or ’randomized controlled trial’:de or ’single-blind procedure’:de or (random* or factorial* or crossover* or cross next/1 over* or placebo* or doubl* near/1 blind* or singl* near/1 blind* or assign* or allocat* or volunteer*):de,ab,ti) cinahl (mh "colic" or mh "kidney calculi+" or mh "ureteral calculi" or mh "urolithiasis" or mh "ureteral obstruction" or mh "ureterolithiasis" or ti (((renal or kidney or ureteral or ureteric or urinary) and (colic or colics or pain or stone or stones or calculus or calculi)) or nephrolithiasis or "tract stone" or "tract stones" or "acute pain") or ab (((renal or kidney or ureteral or ureteric or urinary) and (colic or colics or pain or stone or stones or calculus or calculi)) or urolithiasis or nephrolithiasis or "tract stone" or "tract stones" or "acute pain" or "abdominal pain" or "abdominal cramps" or "abdominal cramping")) and (mh "lidocaine" or tx (lidocaine or lignocaine or xylocaine or lignocain or xylocain or xyloneural or octocaine or xylocitin)) and (mh "randomized controlled trials" or mh "clinical trials" or mh "double-blind studies" or mh "triple-blind studies" or mh "therapeutic trials" or mh "drug therapy+" or tx (randomized or placebo or randomly or trial or groups)) central (lidocaine or lignocaine or xylocaine or lignocain or xylocain or xyloneural or octocaine or xylocitin).mp. and ((renal or kidney or ureteral or ureteric or urinary) and (colic or colics or pain or stone or stones or calculus or calculi)).mp. or (urolithiasis or nephrolithiasis or "tract stone" or "tract stones" or "acute pain" or "abdominal pain" or "abdominal cramps" or "abdominal cramping").mp. china national knowledge infrastructure (chkd-cnki) (lidocaine and renal) or (ropivacaine and renal) or bupivicaine or articaine or mepivacaine or prilocaine or cinchocaine or etidocaine directory of open access journals (doaj) (lidocaine and renal and colic) or (ropivacaine and (intravenous or renal)) or bupivacaine or articaine or mepivacaine or prilocaine or cinchocaine or etidocaine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1):e27 information/chinese scientific journals database (csjdvip) ((bupivicaine or articaine or ropivacaine) and (renal or colic or stone or lithiasis)) or (lidocaine or articaine or mepivacaine or prilocaine or cinchocaine or etidocaine) ieee-xplorer renal colic or (lidocaine and renal) or bupivacaine or articaine or mepivacaine or prilocaine or ropivacaine or cinchocaine or etidocaine korean journal database (kci) renal colic or (lidocaine and renal) or ((bupivacaine or ropivacaine) and intravenous) or articaine or mepivacaine or prilocaine or cinchocaine or etidocaine lilacs (tw:(((renal or kidney or ureteral or ureteric or urinary) and (colic or colics or pain or stone or stones or calculus or calculi)).mp. or (urolithiasis or nephrolithiasis or "tract stone" or "tract stones" or "acute pain" or "abdominal pain" or "abdominal cramps" or "abdominal cramping"))) and (tw:(lidocaine or lignocaine or xylocaine or lignocain or xylocain or xyloneural or octocaine or xylocitin)) or (articaine and intravenous) or (mepivacaine and intravenous and (renal or stone or lithiasis or colic)) or (prilocaine and intravenous and renal) or (ropivacaine and intravenous and renal) or (cinchocaine and intravenous) or (etidocaine and intravenous) magiran renal colic or (lidocaine and renal) or bupivacaine or articaine or mepivacaine or prilocaine or ropivacaine or cinchocaine or etidocaine russian science citation index (rsci) renal colic or (lidocaine and renal) or bupivacaine or articaine or mepivacaine or prilocaine or ropivacaine or cinchocaine or etidocaine scientific electronic library online (scielo) renal colic or (lidocaine and renal) or bupivacaine or articaine or mepivacaine or prilocaine or ropivacaine or cinchocaine or etidocaine scientific information database (sid) renal colic or (lidocaine and renal) or bupivacaine or articaine or mepivacaine or prilocaine or ropivacaine or cinchocaine or etidocaine tubitak ulakbim renal colic or (lidocaine and renal) or ((prilocaine or ropivacaine) and intravenous) or articaine or mepivacaine or bupivacaine or cinchocaine or etidocaine web of science ts=(((renal or kidney or ureteral or ureteric or urinary) and (colic or colics or pain or stone or stones or calculus or calculi)) or urolithiasis or nephrolithiasis or tract stone or tract stones or acute pain or abdominal pain or abdominal cramps or abdominal cramping) and ts=(lidocaine or lignocaine or xylocaine or lignocain or xylocain or xyloneural or octocaine or xylocitin) and ts= clinical trial* or ts=research design or ts=comparative stud* or ts=evaluation stud* or ts=controlled trial* or ts=follow-up stud* or ts=prospective stud* or ts=random* or ts=placebo* or ts=(single blind*) or ts=(double blind*) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declaration references march 16, 2020 total lab-confirmed cases 14,991 total associated deaths 853 total recovered cases 4,996 new cases 1,053 the age distribution of covid-19 cases seems more asymmetric than that of lab-negative pneumonia cases. the association of the cvid-19 with older ages, as well as the lower frequency of the disease in children, are consistent with reports of other countries. the underlying cause of these observations needs to be investigated. it should be noted that part of the cases currently diagnosed as non-covid-19 pneumonia, might be false negative covid-19 cases. this is especially the case in children and teenagers, as proper pharyngeal sampling in these age groups is not a trivial task. high frequency of hospitalization due to pneumonia is expected in children during the winter because of the anatomy of their respiratory tract. * comorbidities means the presence of at least one underlying disease, including: cardiovascular, liver, kidney, blood, neurological diseases, diabetes, asthma, immunodeficiency, and other chronic diseases. the results show that the prevalence of comorbidities is higher in more severe outcomes. source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1,000 1,500 1 9 -f e b 2 0 -f e b 2 1 -f e b 2 2 -f e b 2 3 -f e b 2 4 -f e b 2 5 -f e b 2 6 -f e b 2 7 -f e b 2 8 -f e b 2 9 -f e b 1 -m a r 2 -m a r 3 -m a r 4 -m a r 5 -m a r 6 -m a r 7 -m a r 8 -m a r 9 -m a r 1 0 -m a r 1 1 -m a r 1 2 -m a r 1 3 -m a r 1 4 -m a r 1 5 -m a r n u m b e r confirmed cases and associated deaths confirmed cases associated deaths 0 5 10 15 20 25 =<9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >= 80 p e rc e n t age group age distribution of hospitalized cases lab negative lab-confirmed female 43% male 57% sex distribution of lab-confirmed cases female 41% male 59% sex distribution of lab-confirmed deaths 24.8 27.5 29.0 22 24 26 28 30 total severe disease death p e rc e n t frequency of comorbidities* in lab-confirmed cases emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 150 emergency (2015); 3 (4): 150-154 original research the effect of blood loss in the presence and absence of severe soft tissue injury on hemodynamic and metabolic parameters; an experimental study ali mohammad moradi1, omid aj1, shahram paydar1*, farzaneh ketabchi2, seyed mostafa sheid moosavi2, shahram bolandparvaz1, hamid reza abassi1, aryan dokht tamadon3, davood mehrabani3 1department of surgery, trauma research center, shiraz university of medical sciences, shiraz, iran. 2department of physiology, school of medicine, shiraz university of medical sciences, shiraz, iran. 3stem cell and transgenic technology research center, shiraz university of medical sciences, shiraz, iran. *corresponding author: shahram paydar, md. trauma research center, shahid rajaei trauma hospital, shahid chamran blvd, shiraz, iran. tel/fax: +987116254206. email: paydarsh@sums.ac.ir received: november 2014; accepted: january 2015 abstract introduction: the effect of severe soft tissue injury on the severity of hemorrhagic shock is still unknown. therefore, the present study was aimed to determine hemodynamic and metabolic changes in traumatic/hemorrhagic shock in an animal model. methods: forty male rats were randomly divided into 4 equal groups including sham, hemorrhagic shock, soft tissue injury, and hemorrhagic shock + soft tissue injury groups. the changes in blood pressure, central venous pressure (cvp) level, acidity (ph), and base excess were dynamically monitored and comparedsented. results: mean arterial blood pressure decreased significantly in hemorrhagic shock (df: 12; f=10.9; p<0.001) and severe soft tissue injury + hemorrhagic shock (df: 12; f=11.7; p<0.001) groups 15 minutes and 5 minutes after injury, respectively. a similar trend was observed in cvp in severe soft tissue injury + hemorrhagic shock group (df: 12; f=8.9; p<0.001). after 40 minutes, ph was significantly lower in hemorrhagic shock (df: 12; f=6.8; p=0.009) and severe soft tissue injury + hemorrhagic shock (df: 12; f=7.9; p=0.003) groups. base excess changes during follow ups have a similar trend. (df: 12; f=11.3; p<0.001). conclusion: the results of this study have shown that the effect of hemorrhage on the decrease of mean arterial blood pressure, cvp, ph, and base excess is the same in the presence or absence of soft tissue injury. key words: shock, hemorrhagic; soft tissue injuries; hemodynamics cite this article as: moradi am, aj o, paydar sh, et al. the effect of blood loss in the presence and absence of severe soft tissue injury on hemodynamic and metabolic parameters in an experimental rat model. emergency. 2015;3(4):150-4. introduction: emorrhage is responsible for about 40% of trauma deaths, 33% to 56% of which happen during the pre-hospital period (1). on average, 1 in every 4 patients affected by severe trauma, suffers from coagulopathy. coagulopathy and severe hemorrhage plays an important role in determining the final outcome of the patient, their mortality and disability (24). soft tissue injury is one of the most important injuries that can lead to coagulopathy (5-9) as it can activate both the coagulation pathway and the fibrinolytic system (10). but the effect of severe tissue injury on the severity of hemorrhagic shock is still not known. only in one study it has been demonstrated that the existence of severe tissue injury can decrease the cardiovascular responses in shock and correct bradycardia and hypotension to some extent (11). but other studies have expressed that the physiologic responses observed in traumatic hemorrhagic shock are no different from other kinds of hemorrhagic shock (12-14). to realize the pathophysiology of traumatic/hemorrhagic shock, reductionistic approaches such as animal models were used to study the physiology of “normal” states, to compare with pathologic conditions to follow the alterations after modulation of pathologic states (15-17). a traumatic/hemorrhagic shock animal model was used to simulate the pathophysiological changes characterizing the disease entity in trauma patients with hypovolemic shock (18-22). therefore, this study was carried out to determine hemodynamic and metabolic changes in traumatic/hemorrhagic shock rat model which can be a clinical testing to clarify the process in human patients. methods: study design and setting h this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 151 moradi et al the present experimental study was conducted in accordance with the guidelines of ethics for the evaluation of pain in conscious animals. animal selection, experiments, subsequent care and the sacrifice method were all in line with the guidelines of animal care committee of iran veterinary organization. all experiments were performed under aseptic conditions in laboratory animal center of shiraz university of medical sciences. the study was approved by the ethics committee of the institution. the duration of trials and the number of animals used were reduced to a least possible to minimize animal pain and suffering. during the experiments, the animals were kept one per cage, maintained under controlled environmental conditions (21±2ºc, 65–70% relative humidity; 12 hour light/dark cycle started at 7:00 am) and had free access to water and food. before the experiments, all the animals were deprived of food for 4 hours, but had free access to water to prevent excessive dehydration during starvation. at the end of the procedure, the rats were euthanized under anesthesia or carbon dioxide. animals 40 male sprague-dawley experimental rat models (weight, 200-250 gram) were randomly divided into 4 equal groups: sham (catheter insertions were done, without shock induction), hemorrhagic shock, severe soft tissue injury, and severe soft tissue injury + hemorrhagic shock. animals that died during surgical procedures and rats that lost more than 0.2 ml blood during catheterization or did not have spontaneous breathing 10 minutes after the procedure were excluded. interventions in all procedures, rats were anesthetized with 60 mg/kg intra-peritoneal pentobarbital (sigma chemical company, st, louis, usa) with a 10 mg/kg as maintenance dose (23). body temperature during anesthesia, catheterization, hemorrhage shock, and soft tissue injury was controlled by a heat pad and preserved at 37.0°c. a) catheterization after the confirmation of deep sedation (no response to noxious stimulus) and stability of respiratory rate, three catheters were inserted into femoral artery, carotid artery, and jugular vein (tip of this catheter were placed in the right atrium) for assessing the arterial blood gas sample, blood pressure, and central venous pressure, respectively. in addition, the hemorrhagic shock was induced from the femoral catheter. lidocaine (5mg/kg subcutaneously) was locally used before placing the catheters. catheterization was done with polyethylene tubes number 50 (pe50) cannula (becton dickinson, sparks, md; united states). carotid artery, and jugular vein catheters were connected to pressure transducers and blood pressure analyzer (micro-med, louisville, ky; united states) for continuous monitoring of animals’ hemodynamic state (24). all the catheters were fixed in place using surgical silk sutures. after catheterization, all animals were allowed to stabilize (30 minutes) and baseline hemodynamic parameters were assessed and blood samples were taken (0.2 ml, by insulin syringes). b) inducing the hemorrhagic shock after the stabilization of animals and baseline assessment, hemorrhagic shock was induced using a fixedpressure model. for this purpose, the researcher removed 1 ml blood every minute through the femoral artery catheter, using a 2-ml syringe (pars syringe, tehran, iran). the blood removing was done five times with 10 minute intervals for tuning blood pressure. bleeding was continued until the mean arterial blood pressure reached 25-30 mmhg. heparin (500 u/kg) was intravenously injected through tail vein to prevent blood clotting (24). c) soft tissue injury a close femoral bone fracture and soft tissue injury with no hemorrhage (contusion model) were induced using a blunt guillotine ramming system with a dropped steel weight (0.5kilogram; from a drop height of 15cm). to ensure postoperative stabilization, intramedullary stabilization was performed using a steel pin (24). outcome during the experiment, the changes in blood pressure (bp), central vain pressure (cvp), blood acidity (ph), and base excess (be) were dynamically monitored during 60 minutes. statistical analysis data were analyzed using spss software (version 13, chicago, il, usa) and were expressed as mean ± sem. within-group comparisons were performed by repeated-measures analysis of variance (anova) and inter-group comparisons were done using two-way anova and tukey post hoc test. p value of less than 0.05 was considered statistically significant. results: mean arterial blood pressure significantly dropped in the hemorrhagic shock (df: 12; f=10.9; p<0.001) and severe soft tissue injury + hemorrhagic shock (df: 12; f=11.7; p<0.001) groups 15 minutes and 5 minutes after injury, respectively, and it continued until 60 minutes. this decrease was significant compared to the sham (p<0.001) and soft tissue injury (p<0.001) groups (figure 1). a similar trend was observed in cvp in the severe soft tissue injury + hemorrhagic shock group (df: 12; f=8.9; p<0.001) and in the hemorrhagic shock (df: 12; f=6.4; p<0.001). cvp was significantly reduced from 35 minutes after injury (df: 12; f=7.6; p=0.005). this decrease was significant compared to the sham (p<0.001) and soft tissue injury (p<0.001) groups (figure 2). after 40 minutes, ph was significantly lower in the hemorrhagic shock (df: 12; f=6.8; p=0.009) and severe soft this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (4): 150-154 152 tissue injury + hemorrhagic shock (df: 12; f=7.9; p=0.003) groups compared to the sham group (figure 3). base excess changes during follow ups show a similar trend. compared to the sham animals, hemorrhagic shock (df: 12; f=11.3; p < 0.001) and severe soft tissue injury + hemorrhagic shock (df: 12; f=10.1; p < 0.001) induction lead to significant decrease in base excess in 40 minutes and 60 minutes after injury (figure 4). discussion: the results of this study have shown that the effect of hemorrhage on the decrease of mean arterial blood pressure, central vain pressure, blood acidity, and base excess is the same in the presence or absence of soft tissue injury. in this regard, we can say that soft tissue injury in the absence of hemorrhagic shock has no effect on hemodynamic and metabolic parameters of the blood. one of the major causes of mortality in traumatic patients, is hemorrhagic shock. therefore, evaluating the factors affecting the severity of the shock is of great importance. in the current study, the presence of severe soft tissue injury was studied as a factor that potentially affects hemorrhagic shock. the results from this study showed that severe tissue injury has no effect on blood pressure, central vain pressure, blood acidity, and base excess. while little et al. express that the presence of severe soft tissue injury can influence the cardiovascular * * * * * * * * * * # # # # # # # # # # # # 0 20 40 60 80 100 120 140 160 0 5 10 15 20 25 30 35 40 45 50 55 60 m e a n r te r ia l b lo o d p r e s s u r e ( m m h g ) time (minute) sham sever soft tissue injury hemorrhagic shock sever soft tissue injury+ hemorrhagic shock figure1: comparison of mean arterial blood pressure between the experimented groups. *, shows significant difference of hemorrhagic shock group with the sham group at the same time. #, shows significant difference of severe soft tissue injury + hemorrhagic shock group with the sham group at the same time. # * * * * * # # # # * # # # # # -10 -8 -6 -4 -2 0 2 4 0 5 10 15 20 25 30 35 40 45 50 55 60 m e a n b lo o d p r e s s u r e ( m m h g ) time (minute) sham sever soft tissue injury hemorrhagic shock sever soft tissue injury+ hemorrhagic shock figure 2: comparison of central venous pressure between the experimented groups. *, shows significant difference of hemorrhagic shock group with the sham group at the same time. #, shows significant difference of severe soft tissue injury + hemorrhagic shock group with the sham group at the same time. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 153 moradi et al figure3: comparison of blood ph between the experimented groups. *, shows significant difference of hemorrhagic shock group with the sham group at the same time. #, shows significant difference of severe soft tissue injury + hemorrhagic shock group with the sham group at the same time. response to hemorrhagic shock (11). the reason for this difference might be that little et al. had used ischemia to induce the injuries while most soft tissue injuries induced by crush injury. the mechanisms involved in these models are different and probably that is the reason for the difference seen in the cardiovascular response between the present study and the little et al. study (24). our model of blood withdrawal in the current study combined with active bleeding could produce a severe and reproducible hemorrhagic shock. to date, many hemorrhagic shock–resuscitation models have been established, but none of them covered the important aspects regarding severity, clinical reality, and reproducibility (25-27). our method described here and our experimental findings have led to the creation of a severe but reliable and realistic acute hemorrhagic shock model in rats. in the present experiment, rats reliably survived a hemorrhagic shock-induced decrease in mean arterial pressure. conclusion: the results of this study have shown that the effect of hemorrhage on the decrease of mean arterial blood pressure, central vain pressure, blood acidity, and base excess is the same in the presence or absence of soft tissue injury. in this regard, we can say that soft tissue injury in the absence of hemorrhagic shock has no effect on hemodynamic and metabolic parameters of the blood. acknowledgments: we would like to thank shiraz university of medical sciences for their financial support. conflict of interest: none funding support: none figure 4: comparison of base excess between the experimented groups. *, shows significant difference of hemorrhagic shock group with the sham group at the same time. #, shows significant difference of severe soft tissue injury + hemorrhagic shock group with the sham group at the same time. authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. letson hl, dobson gp. unexpected 100% survival following 60% blood loss using small-volume 7.5% nacl with adenocaine and mg2+ in the rat model of extreme hemorrhagic shock. shock. 2011;36(6):586-94. 2. brohi k, singh j, heron m, coats t. acute traumatic coagulopathy. j trauma acute care surg. 2003;54(6):1127-30. 3. hess jr, brohi k, dutton rp, et al. the coagulopathy of trauma: a review of mechanisms. j trauma. 2008;65(4):74854. 4. saadat s, yousefifard m, asady h, jafari am, fayaz m, hosseini m. the most important causes of death in iranian population; a retrospective cohort study. emergency. 2014;3(1):16-21. 5. harhangi b, kompanje e, leebeek f, maas a. coagulation disorders after traumatic brain injury. acta neurochir (wien). 2008;150(2):165-75. 6. donahue dl, beck j, fritz b, et al. early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans. j neurotrauma. 2014;31(4):404-10. 7. kawasaki t, okamoto k, kawasaki c, sata t. thrombomodulin improved liver injury, coagulopathy, and mortality in an experimental heatstroke model in mice. anesth analg. 2014;118(5):956-63. 8. baratloo a, rahmati f, rouhipour a, et al. correlation of blood gas parameters with central venous pressure in patients with septic shock; a pilot study. bulletin of emergency and trauma. 2014;2(2 apr):77-81. 9. heidari k, hatamabadi h, ansarian n, et al. correlation between capillary and arterial blood gas parameters in an ed. the american journal of emergency medicine. 2013;31(2):326-9. 10. whelihan mf, kiankhooy a, brummel-ziedins ke. thrombin generation and fibrin clot formation under * *# # -25 -20 -15 -10 -5 0 5 0 40 60 b a s e e x c e s s time (minute) sham sever soft tissue injury hemorrhagic shock sever soft tissue injury+ hemorrhagic shock * * # # 6.8 7 7.2 7.4 7.6 0 40 60 p h time (minute) sham sever soft tissue injury hemorrhagic shock sever soft tissue injury+ hemorrhagic shock this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2015); 3 (4): 150-154 154 hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation. j crit care. 2014;29(1):2430. 11. little ra, marshall hw, kirkman e. attenuation of the acute cardiovascular responses to haemorrhage by tissue injury in the conscious rat. q j exp physiol. 1989;74(6):825-33. 12. cherkas d. traumatic hemorrhagic shock: advances in fluid management. emerg med pract. 2011;13(11):1-19. 13. spinella pc, holcomb jb. resuscitation and transfusion principles for traumatic hemorrhagic shock. blood rev. 2009;23(6):231-40. 14. paydar s, bazrafkan h, golestani n, roozbeh j, akrami a, moradi am. effects of intravenous fluid therapy on clinical and biochemical parameters of trauma patients. emergency. 2014;2(2):90-5. 15. hosseini m, karami z, janzadenh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. emergency. 2014;2(4):151-7. 16. ojaghi r, sohanaki h, ghasemi t, keshavarz f, yousefifard m, sadeghipour h. role of low-intensity laser therapy on naloxone-precipitated morphine withdrawal signs in mice: is nitric oxide a possible candidate mediator? lasers med sci. 2014:1-5. 17. ojaghi r, sohanaki h, ghasemi t, keshavarz f, yousefifard m, sadeghipour h. role of low-intensity laser therapy on naloxone-precipitated morphine withdrawal signs in mice: is nitric oxide a possible candidate mediator? lasers med sci. 2014;29(5):1655-9. 18. rixen d, neugebauer eam. changing paradigms in animal models of traumatic/hemorrhagic shock. eur j trauma. 2004;30(5):279-88. 19. angele mk, schneider cp, chaudry ih. bench-to-bedside review: latest results in hemorrhagic shock. crit care. 2008;12(4):218. 20. badin j, boulain t, ehrmann s, et al. relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study. crit care. 2011;15(3):r135. 21. hierholzer c, billiar tr. molecular mechanisms in the early phase of hemorrhagic shock. langenbecks arch surg. 2001;386(4):302-8. 22. lomas-niera jl, perl m, chung c-s, ayala a. shock and hemorrhage: an overview of animal models. shock. 2005;24:33-9. 23. tanideh n, rokhsari p, mehrabani d, et al. the healing effect of licorice on pseudomonas aeruginosa infected burn wounds in experimental rat model. world j plast surg. 2014;3(2):1-8. 24. frink m, andruszkow h, zeckey c, krettek c, hildebrand f. experimental trauma models: an update. biomed res int. 2011;2011:1-15. 25. rönn t, lendemans s, de groot h, petrat f. a new model of severe hemorrhagic shock in rats. comp med. 2011;61(5):41926. 26. suzuki t, kawasaki t, choudhry ma, chaudry ih. role of pparγ in the salutary effects of 17β-estradiol on kupffer cell cytokine production following trauma-hemorrhage. j cell physiol. 2011;226(1):205-11. 27. murao y, hata m, ohnishi k, et al. hypertonic saline resuscitation reduces apoptosis and tissue damage of the small intestine in a mouse model of hemorrhagic shock. shock. 2003;20(1):23-8. introduction: methods: study design and setting animals interventions outcome statistical analysis results: discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: emergency. 2018; 6 (1): e18 le t t e r to ed i to r prevalence of mycoplasma pneumoniae infection in patients with copd exacerbation; a letter to the editor ali reza amiri1, kiarash ghazvini2, hamid zamani moghadam1∗ 1. emergency department, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 2. 1. antimicrobial resistance research center, department of microbiology and virology, medical school, mashhad university of medical sciences, mashhad, iran. received: feruary 2018; accepted: march 2018; published online: 15 march 2018 cite this article as: prevalence of mycoplasma pneumoniae infection in patients with copd exacerbation; a letter to the editor. emergency. 2018; 6(1): e18. dear editor; currently, control and prevention of respiratory illnesses is considered a health priority in most developed countries and managing the risk factors is necessary for improving the population’s health (1, 2). chronic obstructive pulmonary disease (copd) is the 5th cause of death around the world and estimations have indicated that due to an increase in environmental pollution, this disease will become the 3rd cause of death in the future (1, 3). in previous studies, pulmonary infection with mycoplasma pneumoniae has been introduced as one of the causes for copd exacerbation. mycoplasma pneumoniae affects the upper and lower respiratory tract and its clinical manifestation is trachea-bronchitis accompanied by restlessness and dry coughs (4, 5). the pathogenesis spectrum of this bacterium ranges from mild pharyngitis and trachea-bronchitis to acute pneumonia. epidemiologic studies have shown that this bacterium is responsible for more than 20% of community acquired pneumonias (6). in a cross-sectional study by the authors of the present letter, 66 patients over the age of 18 years who had presented to the emergency department of imam reza hospital, mashhad, iran, with diagnosis of copd exacerbation were evaluated. sputum sample of the patients was obtained and sent to the laboratory for performing polymerase chain reaction (pcr). mean age of the patients participating in this study was 67.28 ± 13.68 years (60.6% male). the result of pcr was positive in 6 patients out of the total of 66 patients (9.1%). the results of the present study showed that there was no correlation between age (p=0.18), sex (p=0.25), duration of being affected with copd (p=0.20), consumption of an∗corresponding author: h zamani; emergency department, imam reza hospital, bahar avenue, mashhad, iran. tel: 09155811238 email: zamanimh@mums.ac.ir tibiotics (p=0.35), smoking (p=0.62), opioid abuse (p=0.44), corticosteroid use (p=0.57), underlying illness (p=0.94) and health care–associated pneumonia (hcap) (p=0.46) with mycoplasma infection. however, prevalence of leukocytosis (p=0.01) and myalgia (p=0.02) was significantly higher in the mycoplasma group. numerous studies have confirmed the presence of mycoplasma pneumoniae in exacerbation of copd using serologic diagnosis. for instance, in a study by lieberman et al. (7) prevalence of mycoplasma pneumoniae in patients with copd exacerbation was reported as 14.2% and in meloni et al. (8) study the prevalence of this infection was expressed to be 6.7%. these rates were reported between 5% and 14% in other studies (9-11). thus, it seems that prevalence of mycoplasma is high in copd exacerbation, but there is still no answer to the question if this infection results in exacerbation of copd or not and there is controversy between the studies in this regard (4, 7, 12). therefore, it is suggested to design case-control or cohort studies to find the answer to this question. 1. appendix 1.1. acknowledgements all the personnel of the emergency department of imam reza hospital are thanked for their cooperation in performance of this project. 1.2. author’s contribution all the authors of this article met the criteria of authorship based on the recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. amiri et al. 2 1.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support all the costs of the present study were paid by the researchers. references 1. vogelmeier cf, criner gj, martinez fj, anzueto a, barnes pj, bourbeau j, et al. global strategy for the diagnosis, management and prevention of chronic obstructive lung disease 2017 report. respirology. 2017;22(3):575-601. 2. rootmensen gn, van keimpema ar, looysen ee, van der schaaf l, de haan rj, jansen hm. the effects of additional care by a pulmonary nurse for asthma and copd patients at a respiratory outpatient clinic: results from a double blind, randomized clinical trial. patient education and counseling. 2008;70(2):179-86. 3. hobbs b, zhou j, castaldi p, hawrylkiewicz i, sliwinski p, yim j, et al. variants tagging serpina1 and il27 show significant association with copd in a meta-analysis with over 16,700 subjects. medico. 2016;8(9):10. 4. muro s, tabara y, matsumoto h, setoh k, kawaguchi t, takahashi m, et al. relationship among chlamydia and mycoplasma pneumoniae seropositivity, ikzf1 genotype and chronic obstructive pulmonary disease in a general japanese population: the nagahama study. medicine. 2016;95(15):e3371. 5. layani-milon m-p, gras i, valette m, luciani j, stagnara j, aymard m, et al. incidence of upper respiratory tractmycoplasma pneumoniae infections among outpatients in rhone-alpes, france, during five successive winter periods. journal of clinical microbiology. 1999;37(6):1721-6. 6. waites kb, talkington df. mycoplasma pneumoniae and its role as a human pathogen. clinical microbiology reviews. 2004;17(4):697-728. 7. lieberman d, lieberman d, ben-yaakov m, shmarkov o, gelfer y, varshavsky r, et al. serological evidence of mycoplasma pneumoniae infection in acute exacerbation of copd. diagnostic microbiology and infectious disease. 2002;44(1):1-6. 8. meloni f, paschetto e, mangiarotti p, crepaldi m, morosini m, bulgheroni a, et al. acute chlamydia pneumoniae and mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of copd or asthma: therapeutic considerations. journal of chemotherapy. 2004;16(1):70-6. 9. papaetis g, anastasakou e, tselou t, sotiriou a, rarra v, roussou p, et al. serological evidence of mycoplasma pneumoniae infection in patients with acute exacerbation of copd: analysis of 100 hospitalizations. advances in medical sciences. 2010;55(2):235-41. 10. diederen bm, van der valk p, kluytmans ja, peeters mf, hendrix r. the role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease. european respiratory journal. 2007;30(2):240-4. 11. varma-basil m, dwivedi sk, kumar k, pathak r, rastogi r, thukral s, et al. role of mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease. journal of medical microbiology. 2009;58(3):322-6. 12. varma-basil m, dwivedi sk, kumar k, pathak r, rastogi r, thukral ss, et al. role of mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease. j med microbiol. 2009;58(pt 3):322-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2019; 7 (1): e19 rev i ew art i c l e serum and cerebrospinal fluid levels of s-100β is a biomarker for spinal cord injury; a systematic review and meta-analysis gholamreza faridaalee1, fatemeh keyghobadi khajeh2 ∗ 1. department of emergency, maragheh university of medical sciences, maragheh, iran. 2. department of community medicine, tabriz university of medical sciences, tabriz, iran. received: november 2018; accepted: december 2018; published online: 12 february 2019 abstract: introduction: there is controversy regarding the value of serum or cerebrospinal fluid (csf) levels of s100 calcium-binding protein b (s-100β) in spinal cord injury (sci). for reaching a general conclusion, the present meta-analysis was designed aiming to evaluate the value of serum and csf levels of s-100β protein in detecting the presence of sci in animal studies. methods: an extensive search was performed in medline, embase, scopus and web of science databases. screening articles, summarizing them and entering data to checklist and quality assessment of the mentioned articles were done by 2 independent reviewers. data were analyzed and a pooled standardized mean difference (smd) and 95% confidence interval (95% ci) were presented. results: finally, the data of 7 articles were included in the meta-analysis. serum level of s-100b had increased as a result of sci. during the first 6 hours after injury, the level of this protein was very high (smd=3.8; 95% ci: 2.6 to 5.1; p<0.0001), but as time passed the serum level of the protein had decreased (smd=0.4; 95% ci: -1.2 to 2.0; p=0.65). in addition, csf level of the mentioned protein was very high during the initial 6 hours after injury (smd: 5.8; 95% ci: 3.6 to 8.0), and this elevated level was still observed until 12 hours after injury (smd: 6.5; 95% ci: 3.7 to 9.3; p<0.0001). conclusion: the results of the present systematic review and meta-analysis show that measuring the level of s-100β protein in serum and csf has a potential value in diagnosis of sci in animal models. this biomarker increases during the initial 6 hours following injury and remains high until 24 hours after that. however, more than 24 hours after the injury, serum level of this protein returns to the level of animals without sci. keywords: s100 calcium binding protein beta subunit; spinal cord injuries; animals; s100b protein, rat cite this article as: faridaalee gh, keyghobadi khajeh f. serum and cerebrospinal fluid levels of s-100β is a biomarker for spinal cord injury; a systematic review and meta-analysis. arch acad emerg med. 2019; 7(1): e19. 1. introduction t raumatic spinal cord injury (sci) is among the most serious injuries that deeply affect the health of an individual. prevalence of sci has been reported as 11 to 53 cases for each million population (1). epidemiologic studies performed in the past 3 decades have clearly shown that scis primarily affect young individuals (with the mean age of 29 years) and then impact the 30-45 years age group (2-4). in all age groups, the highest rate of spinal cord injury belongs to incomplete tetraplegia, and after that, complete paraple∗corresponding author: fatemeh keyghobadi khajeh, community department of faculty medicine, tabriz university of medical sciences, golgasht street, tabriz, iran; email: f.keigobadi@yahoo.com; tel/fax: 0413382954009149135765 gia, complete tetraplegia, and incomplete paraplegia are the most common, respectively (5). despite extensive research in the field of scis no effective treatment has been found for restoring motor and sensory functions, yet (6), but considerable advances in looking after and providing care for sci patients has led to a significant decrease in the rate of mortality due to sci (7). after stabilizing the clinical condition in the initial days after spinal cord injury, the family of the patients and the patients themselves want to know if they can walk again or if they will be able to carry out their personal obligations such as eating, taking a bath, and wearing clothes or not (8); therefore, a correct evaluation of the severity and classification of sci for predicting the functional status after spinal cord injury is of importance. currently, classification of scis is done based on american spinal injury association (asia) impairment scale (ais) (9). although ais is currently a gold this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem gh. faridaalee et al. 2 standard in classification of sci, this system has some limitations too (10). therefore, in order to create a more comprehensive classification, the researchers have tried to use various tools such as magnetic resonance imaging (mri) (11-13), electrophysiological evaluations (14-16), and biomarkers (17, 18). biomarkers are secreted to the serum or cerebrospinal fluid (csf) at various stages and in different types of sci. one of the biomarkers, which has received much attention in prediction of presence and severity of the injury is s-100β protein, as studies have shown a rapid increase in its serum level after spinal cord injury (19, 20). yet, there is still no data regarding optimum timing of measuring this protein or the effect of injury severity on its serum or csf level. for reaching a general conclusion, the present study was designed aiming to evaluate the diagnostic value of serum and csf levels of s-100β protein in detecting the presence of sci in animal studies. 2. methods: the present study was designed based on moose guideline, which is a guide for performing systematic review and metaanalysis on observational studies (21). defining pico in the present study is as follows: the problem or the study population includes animals with sci; the intended factor (index test): the level of s-100β protein in serum or cerebrospinal fluid; comparisons (c): comparison is done with a control group free of injury; and the studied outcome (o) includes the severity of injury and presence or absence of sci. 2.1. search strategy for reaching the aims of the present study, an extensive search was performed in the electronic databases and references of related articles. search in grey literature is another strategy used in the present study. search in electronic databases was performed using the systematic method under the guidance of a librarian and supervision of an expert in the field of sci. at this stage, related keywords were selected using mesh and emtree databases, consulting with experts in this regard, and searching in the titles and abstracts of related articles. then search strategy for each database was defined using the guidelines of the same database. methods of search and summarizing data have been reported in previous meta-analyses (22-34). it should be noted that electronic databases of medline, embase, web of science, and scopus were searched until the end of 2017. search strategy in medline database is presented below as a template. 3. selection criteria in the present research, experimental studies performed with the aim of determining the diagnostic accuracy of serum and cerebrospinal fluid levels of s-100β protein in detecting spinal cord injury were included. only the studies that had a control group were included. exclusion criteria consisted of absence of a control group, not reporting the protocol of measuring the biomarker and review articles. 3.1. quality assessment and data extraction screening articles, summarizing them and entering data to checklist and quality assessment of the mentioned articles were done by 2 independent individuals. any disagreement was resolved via discussion with a third researcher. the articles were summarized using a checklist that was designed based on the guidelines of prisma statement (35). extracted data included information regarding study design, characteristics of case and control groups (age, mechanism of spinal cord injury induction), the number of studied cases, and serum and csf levels of s-100β protein. if 2 or more articles were published from the same dataset, the study which had the biggest sample size or the longest follow up was included. if the required data were not presented in the paper, the corresponding author was contacted and asked for the required data. when the evaluated variables were presented based on various subgroups (such as sex and etc.), data were recorded separately. if the results were given as charts, the method of data extraction from charts introduced by sistrom and mergo was used (36). 3.2. quality control of the study the quality was assessed using the criteria proposed by yousefifard et al. (37) and hassannejad et al. (38). for assessing the agreement between the 2 researchers, inter rater reliability was evaluated in quality assessment of the studies (agreement rate: 88%). in case of any disagreement, it was resolved by discussion with a third researcher. 3.3. statistical analyses analyses were done using stata 14.0 statistical software. all studies were summarized and classified based on the studied variables. in the mentioned statistical software, analyses were done using the “metan” command and forest plots of serum and csf levels of s-100β protein in detection of spinal cord injury were drawn. in the present research, depending on the presence or absence of heterogeneity, random effect model or fixed effect model were used, respectively, for performing analyses. for evaluating heterogeneity between the studies, chi square and i2 tests were applied. in cases that heterogeneity was present, subgroup analyses were performed to determine the cause of heterogeneity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e19 figure 1: prisma flow diagram of the present meta-analysis. 4. results: 4.1. study characteristics the search performed in databases yielded 1798 nonredundant records. after screening, finally the data of 7 articles were included in the meta-analysis (39-45) (figure 1). these studies consisted of 136 healthy animals and 128 animals with sci. 6 studies were performed on rats (39-44) and only 1 study was performed on pigs (45). injury severity was moderate to severe. the model of spinal cord injury used was contusion in 4 studies (39-41, 44), compression in 2 studies (42, 43), and armor blunt trauma in one study (45). time of sampling and evaluation of s-100β protein varied from 30 minutes to 240 hours. for performing analyses, time to sample was classified into 4 groups of 0 to 6 hours after injury, 12 hours after injury, 24 hours after injury and more than 24 hours after injury. it should be noted that 4 studies had assessed serum levels of s-100β protein (40-43), one study had evaluated csf level of this protein (39) and two had evaluated both (44, 45). summary of the mentioned variables are reported in table 1. 4.2. source of bias in quality control of the studies, the method suggested by hassannejad et al. and yousefifard et al. was applied. findings of this section have been presented in figure 2. as can be seen, no study had attempted to calculate sample size, none had presented findings regarding the mortality of the animals, and quality of the studies regarding post-operative care of the animals was poor. it should be noted that conflict of interest was reported in only one study. out of the 19 items being evaluated in the quality assessment of the articles, 11 items were desirable in almost all studies. heterogeneity test showed that in evaluating both the diagnostic value of serum level (i2=86.3; p<0.0001) and diagnostic value of csf level (i2=79.5; p<0.0001) of s-100β protein, significant heterogeneity was present. therefore, subgroup analysis was performed. 5. meta-analysis 5.1. serum value of s-100β protein in detection of sci the findings showed that sci can be detected via serum level of s-100β protein. in other words, serum level of this prothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem gh. faridaalee et al. 4 table 1: characteristics of included studies author; year; country species sample size (no-sci / sci) weight severity sci-model time to sample (hours) method of s-100β analysis location of biomarker cao f; 2008; china (39) spraguedawley rat 40 / 40 200 gr moderate to severe contusion 0.5 to 24 elisa csf ersahin; 2011; turkey (40) wistar albino rat 8 / 8 250-300 gr moderate contusion 168 elisa serum ma; 2001; sweden (42) spraguedawley rat 48 / 40 200-300 gr moderate compression0 to 240 elisa serum loy; 2005; usa (41) spraguedawley rat 12 / 12 190-230 gr moderate to severe contusion 6 to 24 elisa serum schultke; 2010; canada (43) wistar rat 9 / 9 286-310 gr moderate compression6 to 24 elisa serum yang; 2017; usa (44) fischer rat 5 / 5 220-250 gr moderate to severe contusion 4 to 68 elisa csf and serum zhang; 2011; china (45) white pig 14 / 14 41.5-61 kg severe armor blunt trauma 0.5 to 3 elisa csf and serum csf: cerebrospinal fluid; elisa: enzyme-linked immunosorbent assay table 2: subgroup analysis of s-100β level in traumatic spinal cord injury variable heterogeneity p for heterogeneity effect size p serum level of s-100β severity of injury moderate 78.5% <0.0001 1.6 (0.8 to 2.4) <0.0001 severe 91.0% <0.0001 3.4 (1.6 to 5.4) <0.0001 significance level between groups 0.040 injury model contusion 73.9% <0.0001 1.8 (1.0 to 2.6) <0.0001 compression 82.8% <0.0001 1.6 (0.3 to 2.9) <0.0001 significance level between groups 0.122 time to sample after injury 0 to 6 hours 86.3% <0.0001 3.8 (2.6 to 5.1) <0.0001 12 hours 40.1% 0.196 2.7 (0.5 to 4.9) 0.018 24 hours 68.8% 0.007 1.5 (0.5 to 2.5) 0.003 more than 24 hours 86.6% <0.0001 0.4 (-1.2 to 2.0) 0.652 significance level between groups 0.003 csf level of s-100β severity of injury moderate 70.1% <0.0001 4.1 (2.4 to 5.8) <0.0001 severe 85.1% <0.0001 4.1 (2.1 to 6.2) <0.0001 significance level between groups 0.925 time to sample after injury 0 to 6 hours 79.6% <0.0001 5.8 (3.6 to 8.0) <0.0001 12 hours 0.0% 0.420 6.5 (3.7 to 9.3) <0.0001 24 hours 0.0% 0.777 2.7 (1.7 to 3.7) <0.0001 more than 24 hours 87.4% 0.005 0.8 (-2.2 to 3.8) 0.584 significance level between groups 0.051 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e19 figure 2: quality assessment of the included studies. tein increases as a result of sci (figure 3). during the first 6 hours after injury, the level of this protein was very high (smd=3.8; 95% ci: 2.6 to 5.1; p<0.0001), but as time passed the serum level of the protein had decreased and after more than 24 hours had passed, its measure was almost the same as the animals without a spinal cord injury (smd=0.4; 95% ci: -1.2 to 2.0; p=0.65). it should be noted that the serum level of this protein in severe injuries (smd=3.4; 95% ci: 1.6 to 5.4; p<0.0001) was many times more than moderate injuries (smd=1.6; 95% ci: 0.8 to 2.4; p<0.0001) (p=0.04) (table 2). 5.2. csf value of s-100β protein in detection of sci just like the serum level, csf level of s-100β protein had significantly increased following spinal cord injury. csf level of the mentioned protein was very high (smd: 5.8; 95% ci: 3.6 to 8.0), and this increased level was still observed until 12 hours after injury (smd: 6.5; 95% ci: 3.7 to 9.3; p<0.0001). however, 24 hours after injury this rate had decreased (smd: 2.7; 95% ci: 1.7 to 3.7; p<0.0001) and after more than 24 hours, csf level of this protein in animals with sci was not different from the healthy animals group (smd: 0.7; 95% ci: -2.2 to 3.8; p=0.584) (figure 4). 6. discussion most studies in the field of biomarkers related to sci are performed on nse and s-100β, but since these two biomarkers have low specificity in patients who have multiple traumas simultaneously (18) (these biomarkers also increase in traumas other than sci), performing a systematic review seemed necessary for reaching a definite conclusion regarding the effectiveness of these biomarkers in detection of sci; therefore, the present systematic review evaluated the diagnostic value of serum and cerebrospinal fluid levels of s-100β protein in detection of sci for the first time. the results of this study this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem gh. faridaalee et al. 6 figure 3: forest plot of serum s-100β in spinal cord injury. animal studies showed that the mean level of serum s-100β is higher in animals with spinal cord injury during the first 24 hours after trauma. ci: confidence interval; smd: standardized mean difference. figure 4: forest plot of csf s-100β in spinal cord injury. animal studies showed that the mean level of csf s-100β is higher in animals with spinal cord injury during the first 24 hours after trauma. ci: confidence interval; smd: standardized mean difference. show that s-100β protein levels in serum and csf increase in animals following sci induction and have diagnostic value. during the initial 6 hours of sci, the level of this protein is very high in csf and serum, but with time passing, the serum level of this protein decreases and at times after 24 hours, its rate does not differ from animals without sci. s-100β protein, which is a calcium-binding protein, is mostly present in the cytoplasm of glial cells. since the blood-brain barrier (bbb) is not permeable to this protein, the measure of this protein in serum and csf is normally zero and therefore, following injury to the central nervous system and damage of bbb, the level of this biomarker increases in csf and serum depending on the severity of injury (46, 47). the present systematic review has evaluated the level of s-100 protein in animal models of sci. in the systematic review performed by salehpoor et al. in 2015, the level of various biomarkers including s-100 has been evaluated in traumatic brain injuries (tbis) in clinical studies and it has been shown that the serum level of s-100 in children and adults strongly correlates with tbi diagnosis and prediction of its outcome (48). the systematic review by thelin et al. in 2017 showed that serum level of biomarkers such as s-100 is effective in monitoring brain injuries in adults (49). a systematic review by lugones et al. in 2018 presented the same results in children (50). since spinal cord is a part of the central nervous system just like the brain and has bbb, the results of our study can also be in line with the existing studies and damage to bbb following sci can be a logical explanation for the results of our study. various methods such as standard scoring system, magnetic resonance imaging (mri), and electrophysiologic techniques are used for detection and classification of sci. with the invention of diagnostic methods with high accuracy, such as enzyme-linked immunosorbent assay (elisa), immunoblotting, proteomics and genomics, one diagnostic method for sci is evaluating the level of biomarkers in blood and csf (51). the most famous study in the field of assessing the correlation between biomarkers and diagnosis of sci might be the study by guez et al. in 2003. this research team proposed and evaluated the idea of assessing the level of biomarkers in csf as a diagnostic tool for sci (52). in that study, the level of nfl and gfap was evaluated in csf of patients with acute sci and it was revealed that measuring these biomarkers in csf can be used as a tool for quantitative classification of injured neurons following various degrees of sci. in 2010, for the first time, in addition to csf, these biomarkers were measured and assessed in blood of patients with various sci severities and with acceptable sample size by kwon et al. the results of the study expressed that measurement of il-8, s-100β, and gfap in csf during the initial 24 hours following sci is effective in determining the severity of injury and monitoring improvement process (53). kwon et al. also extensively assessed the value of measuring biomarkers in csf and serum following sci in a review in 2011 and finally stated that considering the scarcity of studthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e19 ies to date, reaching a final conclusion regarding the value of measuring biomarkers in serum and csf for classification of sci severity and monitoring of the improvement process is not possible yet (17). in addition to their diagnostic value, biomarkers are also useful in choosing a strategy for selecting a treatment plan in sci. since the outcomes of the primary phase of sci are unavoidable, the main goal of treatment in sci is preventing the secondary phase during which many things happen on the molecular level and the level of neural biomarkers is extremely mutable. therefore, these biomarkers can be studied in the second phase for following the interventions performed (54, 55). 7. limitations high level of heterogeneity was among the limitations of the present study. one of the sources of the high heterogeneity was the time of measuring serum and csf levels of this protein. however, other factors such as difference in techniques used for evaluating the level of s-100β, difference between various species and etc. might be among other factors causing heterogeneity. in this study, all efforts were made to also include clinical studies that had evaluated the diagnostic value of s-100β in diagnosis of sci. yet, due to the small number of these studies, various methodologies for performing the study and a high level of diversity in the studied sci patient population, this could not be done. 8. conclusion the results of the present systematic review and metaanalysis show that measuring the level of s-100β protein in serum and csf has diagnostic value in diagnosis of sci in animal models. this biomarker increases during the initial 6 hours following injury and remains high until 24 hours after it. however, more than 24 hours after the injury, serum level of this protein returns to the level of animals without sci. 9. appendix 9.1. acknowledgements we are pleased to acknowledge dr. mahmoud yousefifard as the third reviewer of the present work. 9.2. authors contributions study concept and design: both authors reading and selection of appropriate aticles: both authors analysis and interpretation of data: gholamreza faridaalee drafting of the manuscript: gholamreza faridaalee critical revision of the manuscript for important intellectual content: both authors authors orcids gholamreza faridaalee: 0000-0002-9990-4936 fatemeh keyghobadi khajeh: 0000-0003-0257-289x 9.3. funding support maragheh university of medical sciences. 9.4. conflict of interest no conflict of interest. references 1. wyndaele m, wyndaele j-j. incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? spinal cord. 2006;44(9):523. 2. norton l. spinal cord injury, australia, 2007-08: australian institute of health and welfare canberra; 2010. 3. van middendorp j, hosman a, pouw m, van de meent h. is 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ca. secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. acta neurobiol exp (wars). 2011;71(2):281-99. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: selection criteria results: meta-analysis discussion limitations conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 137 emergency (2015); 3 (4): 137-140 original research comparing the antiemetic effects of ondansetron and metoclopramide in patients with minor head trauma majid zamani, behnam namdar*, reza azizkhani, omid ahmadi, mehrdad esmailian department of emergency medicine, al-zahra hospital, isfahan university of medical sciences, isfahan, iran. *corresponding author: behnam namdar; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989132587956; fax: +983117923445; email: behnamnamdar@ymail.com received: december 2014; accepted: january 2015 abstract introduction: nausea and vomiting are the most common complications after minor head trauma that increases the risk of intracranial pressure rising. therefore, the present study was aimed to compare the antiemetic effects of metoclopramide and ondansetron in the treatment of post-traumatic nausea and vomiting. methods: the study was a controlled, randomized, double blind clinical trial, which was conducted in the first 6 months of 2014 in emergency department al-zahra and kashani hospitals in isfahan, iran. the patients with minor head trauma associated with nausea and vomiting were randomly divided into 2 groups: treatment with metoclopramide (10mg/2ml, slow injection) and treatment with ondansetron (4mg/2ml, slow injection). the comparison between the 2 groups was done regarding antiemetic efficacy and side effects using spss 21 statistical software. results: 120 patients with minor head trauma were distributed and studied into two groups of 60 patients (mean age 35.6±14.1 years; 50.0% male). administration of both ondansetron and metoclopramide significantly reduced the severity of nausea (p<0.001). changes in the severity of nausea in both groups before and after the treatment revealed that nausea had been decreased significantly in both groups (p < 0.001). the incidence of fatigue (p=0.44), headache (p=0.58) and dystonia (p=0.06) had no significant difference in the two groups but the incidence of drowsiness and anxiety in the metoclopramide group was significantly higher (p < 0.001). conclusion: the present study indicated that the treatment effectiveness of ondansetron and metoclopramide are similar. however, incidence of drowsiness and anxiety in the metoclopramide was considerably higher. since these complications can have adverse effects on the treatment of patients with brain injury, it is suggested that it may be better to use ondansetron in these patients. key words: head injuries, closed; nausea; vomiting; multiple trauma cite this article as: zamani m, namdar b, azizkhani r, ahmadi o, esmailian m. comparing the antiemetic effects of ondansetron and metoclopramide in patients with minor head trauma. emergency. 2015;3(4):137-40. introduction: n general, brain injury can occur due to sudden and severe head strike to a hard object, which can be mild, moderate or severe (1). the main causes of head injury include traffic accidents, falling from heights, physical violence, accidents at work, inside home accidents and during exercise incidents. however, the most important cause of head trauma in iranian population is traffic accident (2). among the warning signs of head trauma are nausea, vomiting, dizziness, headache, blurred vision, and loss of balance, difficulty in sleeping, memory problems, tinnitus and fatigue (3). nausea and vomiting are the most common complications after minor head trauma that in addition to severe harassment of patients increases the risk of aspiration and intracranial pressure rising. ondansetron and metoclopramide are two available antiemetic agents in the emergency department. ondansetron is a serotonin 5-ht3 receptor antagonist, which connects to the peripheral and central receptors of serotonin (1). this drug is mostly used in nausea and vomiting after chemotherapy and surgery (2). it does not have any effect on dopamine receptors thus; it does not have extra pyramidal effect (3). its maximum effect is in intravenous administration right after the injection. this drug has a half-life of 2-7 hours and is metabolized in the liver where it changes into glucuronide and sulfate which is inactive. its most common side effects include headaches, fatigue, diarrhea, constipation, dizziness and anxiety. the recommended dose for the treatment of nausea and vomiting is 4-8 milligrams (4, 5). metoclopramide as an old antiemetic is mostly used in high doses, before chemotherapy and for i this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com zamani et al 138 nausea and vomiting caused by various reasons (6-8). this drug blocks the dopamine receptors on the peripheral and central dopamine receptors and increases the movement of the upper gastrointestinal tract without increasing secretion (9, 10). its intravenous absorption takes about 3 minutes and the peak of its effect is about 15 minute. this drug is metabolized in the liver and its half-life is approximately 4-5 hours (11). its most common side effects include dystonia < 10%, fatigue, drowsiness, and flushing. based on the above-mentioned reasons, the present study was aimed to compare the antiemetic effects of metoclopramide and ondansetron in the treatment of post head trauma nausea and vomiting. methods: study design and setting the study was a controlled, randomized, double blind clinical trial, which was conducted in the first 6 months of 2014 in al-zahra and kashani hospitals in isfahan, iran. the present study was supervised and accepted by the ethics committee of isfahan university of medical sciences. all the participants have consciously signed a written consent before entering the study. the study was registered in iranian registry of clinical trial (irct number: irct2015043012072n6). participants the studied population included patients with minor head trauma associated with nausea and vomiting who were referred to the emergency department . minor head trauma has been considered as gcs 14-15. the patients older than 15 years old, with minor head trauma, nausea and vomiting, and a triage level of 3 or higher based on emergency severity score were included. the exclusion criteria were considered as follow: hemodynamic instability; pregnancy/lactation; any neurologic deficit; restless leg syndrome; alcohol usage; consumption of any antiemetic drugs during the 8 hours prior to admission; previous administration of intravenous fluids; motion/vertigo related nausea and vomiting; chemotherapy or radiotherapy; inability to complete and understand study explanations or outcome measures; finally allergy or previous adverse reactions to metoclopramide or ondansetron; and lack of data regarding demographic data and the severity of nausea and vomiting based on the visual analog scale (vas). the qualified patients then entered the study using convenience sampling. permuted-block randomization was done with a bock size of 6. intervention the patients were randomly divided into 2 groups: treatment with metoclopramide (10mg/2ml, slow injection) and treatment with ondansetron (4mg/2ml, slow injection). preparing the drugs was done by an independent pharmacologist in a sterilized manner. for the study to be double –blind, the drugs were packed in nameless syringes, and in numbered, dark packs and only the main researcher knew about the drug content. the drugs were kept in a fridge in the emergency department. the patients and the other researchers were blind to the drug content and the treatment group. drug information and treatment group of the patients would only be revealed if the patients showed extrapyramidal side effects of the drugs, which did not happen in this study. drug administration and patient assessment was done by emergency medicine residents. 20 minutes post drug administration, nausea level was measured again. if the severity of nausea had not decreased at least by 20 mm compared to the rate before the treatment intervention, a rescue dose (4mg ondansetron) would be prescribed for the patient. measurements nausea severity was measured using self-rated visual analogue scale (vas) before and 20 minutes after the intervention. vas was a standard 100 mm (mm) method on which the left side indicated no nausea and the right side was an indicator of the worst nausea possible. using this scale for assessing nausea severity was accepted in previous studies. according to these studies the minimum difference in nausea severity counted as clinically significant, was set at 20 mm. nausea severity was divided into 3 levels: severe nausea (vas > 70 mm), moderate nausea (50 mm < vas <70 mm) and mild nausea (vas < 50 mm). outcomes the primary outcome was defined as mean nausea severity according to vas in the twentieth minute post drug administration. secondary outcomes included needing a rescue dose and side effects of the drugs. statistical analysis population sample size for each group was determined based on comparing mean nausea severity between the 2 treatment groups. based on previous studies (12), mean and standard deviation of nausea severity reduction before and after ondansetron administration was 40 mm and 24 mm respectively. based on this, by considering α = 0.05 and 90% power (β = 0.1), the sample size of 43 patients in each group was sufficient. finally, 60 patients were included in each group. the data were analyzed using spss 21.0. nausea severity was expressed as mean and standard deviation. to compare the 2 groups, t-test was used and for comparing the effects of the drug before and after administration, paired t-test was used. the drug side effect was also expressed as frequency and percentage. the comparison between the 2 groups was done using the chi square, the fisher exact, or mannwhitney u test. in all the analyses, p < 0.05 was defined as the level of significance. results: finally, 120 patients with minor head trauma were distributed and studied into two groups of 60 patients (mean age 35.6 ± 14.1 years; 50.0% male). mean age of metoclopramide and ondansetron treated groups were this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 139 emergency (2015); 3 (4): 137-140 36.1 ± 14.0 and 35.0 ± 14.2 years, respectively (p = 0.69). the sex distribution in ondansetron (45.0% male) and metoclopramide groups (55.0% male) had no significant difference. administration of both ondansetron and metoclopramide significantly reduced the severity of nausea (p < 0.001). the average score of nausea severity before the injection of ondansetron and metoclopramide in the groups were 89.3±12.5 and 85.3 ± 14.9, respectively (p = 0.11). after intervention, nausea in the two groups were 32.3 ± 14.8 and 36. 5 ± 17.8, respectively (p = 0.17) (figure 1). before intervention 51 patients (85.0%) of the ondansetron group and 47 patients (78.3%) of the metoclopramide group had severe nausea (vas > 70 mm) (p = 0.35). after intervention only 2 patients (3.3%) of the ondansetron treated and 5 patients (8.3%) of the metoclopramide treated group had severe nausea (p = 0.16). however, changes in the severity of nausea in both groups before and after the treatment revealed that nausea had been decreased significantly in both groups (p < 0.001) (figure 2). the incidence of fatigue (p = 0.44), headache (p=0.58) and dystonia (p = 0.06) had no significant difference in the two groups but the incidence of drowsiness and anxiety in the metoclopramide group was significantly higher (p < 0.001) (table 1). 2 (1.7%) patients needed the rescue dose which were in the metoclopramide treated group (p = 0.50). discussion: the present study showed that the antiemetic effect of ondansetron and metoclopramide in patients with minor head trauma is the same. the frequency of severe nausea in the ondansetron group reduced from 85% to 3.3% while in the metoclopramide group, reduced from 78.3% to 8.3%. the incidence of drowsiness and anxiety were significantly lower in the ondansetron treated patients. the antiemetic effects of ondansetron and metoclopramide have been compared in various studies, the results of which are in line with the current study. for instance, a study by pitts et al. reveals that the effectiveness of ondansetron and metoclopramide compared to the placebo, show no significant difference in decreasing nausea and vomiting in the patients admitted to the emergency department (13). also egerton-warburton et al. expressed in their study that the antiemetic effects of ondansetron and metoclopramide were no different compared to the placebo (14). in addition, barrett et al. and al-ansari et al. have reported similar results (12, 15). in the present study, mean pain relief was 48.8 mm in the metoclopramide group and 57.0 mm in the ondansetron ones which was significantly different from the results of the mentioned studies. in this regard, egerton-warburton et al. showed that administering 4mg ondansetron and 20mg metoclopramide resulted in a 27 mm and 28 mm decrease in nausea severity, respectively (2). these levels in the barrett et al. study was 40 mm for ondansetron and 32 mm for metoclopramide (15). concerning the drugs’ side effects, patanwala et al. propose in their review study that due to safety, ondansetron is a better choice for the first line of treatment for decreasing nausea and vomiting in the patients admitted to the emergency department (16). the present study also showed that compared to metoclopramide, ondansetron administration, showed less side effects. in addition, in a study by egerton-warburton et al. 6 patients showed side effects in the group treated with metoclopramide, table 1: distribution of clinical signs in the two groups variable metoclopramide n (%) ondansetron n (%) p age (mean ± sd) 36.1 ± 14.0 35.0 ± 14.2 0.69 gender male 27 (45.0) 33 (55.0) 0.27 female 33 (55.0) 27 (45.0) headache yes 30 (50.0) 33 (55.0) 0.58 no 30 (50.0) 27 (45.0) drowsiness yes 26 (43.3) 8 (13.3) <0.001 no 34 (56.7) 52 (86.7) fatigue yes 23 (38.3) 19 (31.7) 0.44 no 37 (61.7) 41 (68.3) anxiety yes 37 (61.7) 11 (18.3) <0.001 no 23 (38.3) 49 (81.7) dystonia yes 5 (8.3) 0 (0.0) 0.057 no 55 (91.7) 60 (100.0) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com zamani et al 140 whereas only 2 showed side effects in the group treated with ondansetron (14). a shortcoming in the present study was the lack of a placebo group. if such a group was studied, an assessment of the placebo effect would have been possible. in addition, since convenience sampling was used, selection bias is possible. conclusion: the present study indicated that the treatment effectiveness of ondansetron and metoclopramide are similar. however, incidence of drowsiness and anxiety in the metoclopramide was considerably higher. since these complications can have adverse effects on the treatment of patients with brain injury, it is suggested that it may be better to use ondansetron in these patients. findings. acknowledgments: the authors appreciate the insightful cooperation of staffs of the emergency department. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. cooke ce, mehra iv. oral ondansetron for preventing nausea and vomiting. am j hosp pharm. 1994;51(6):762-71. 2. carlisle jb, stevenson ca. drugs for preventing postoperative nausea and vomiting. cochrane database syst rev. 2006 (3):cd004125. 3. naumann cr, zelig c, napolitano pg, ko cw. nausea, vomiting, and heartburn in pregnancy: a prospective look at risk, treatment, and outcome. j matern fetal neonatal med. 2012;25(8):1488-93. 4. keller k, beule j, dippold w. cyclic vomiting syndrome in adults. wien med wochenschr. 2013;163(21-22):514-6. 5. hejazi ra, mccallum rw. cyclic vomiting syndrome: treatment options. exp brain res. 2014;232(8):2549-52. 6. yadav deepak r, ayyappan t, shanmugam s, sundaramoorthy k, vetrichelvan t. development and in-vitro evaluation of buccoadhesive metoclopramide hydrochloride tablet formulations. development. 2011;3(1):516-25. 7. olver i, clark-snow ra, ballatori e, espersen bt, bria e, jordan k. guidelines for the control of nausea and vomiting with chemotherapy of low or minimal emetic potential. support care cancer. 2011;19(1):33-6. 8. snow v, weiss k, wall em, mottur-pilson c. pharmacologic management of acute attacks of migraine and prevention of migraine headache. ann intern med. 2002;137(10):840-9. 9. yi hs, kim hs, seo mr. trial of oral metoclopramide on diurnal bruxism of brain injury. ann rehabil med. 2013;37(6):871-4. 10. faridaalaee g, rahmani sh, mehryar h, et al. comparison of intravenous metoclopramide and acetaminophen in primary headaches: a randomized controlled trial. emergency. 2015;3(2):67-71. 11. livezey mr, briggs ed, bolles ak, nagy ld, fujiwara r, furge ll. metoclopramide is metabolized by cyp2d6 and is a reversible inhibitor, but not inactivator, of cyp2d6. xenobiotica. 2013;44(4):309-19. 12. al-ansari k, alomary s, abdulateef h, alshawagfa m, kamal k. metoclopramide versus ondansetron for the treatment of vomiting in children with acute gastroenteritis. j pediatr gastroenterol nutr. 2011;53(2):156-60. 13. pitts sr. neither ondansetron nor metoclopramide reduced nausea and vomiting in the emergency department. ann intern med. 2014;161(12):jc3. 14. egerton-warburton d, meek r, mee mj, braitberg g. antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. ann emerg med. 2014;64:526-32. 15. barrett tw, dipersio dm, jenkins ca, et al. a randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults. am j emerg med. 2011;29(3):247-55. 16. patanwala ae, amini r, hays dp, rosen p. antiemetic therapy for nausea and vomiting in the emergency department. j emerg med. 2010;39(3):330-6. figure 1: mean changes of nausea severity before and after intervention in the 2 groups figure 2: frequency of nausea before and after treatment in both groups 0 20 40 60 80 100 120 before intervention after intervention m e a n n a u s e a s e v e r it y time ondansetron metoclopramide 0 9 51 23 35 2 0 43 47 17 38 5 0 10 20 30 40 50 60 mild moderate severe mild moderate severe before intervention after intervention n u m b e r o f p a ti e n ts ondansetron metoclopramide introduction: methods: study design and setting participants intervention measurements outcomes statistical analysis results: discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: archives of academic emergency medicine. 2019; 7 (1): e5 or i g i n a l re s e a rc h prevalence of depression and personality disorders in the beginning and end of emergency medicine residency program; a prospective cross sectional study farhad rahmati1, saeed safari1, behrooz hashemi1, alireza baratloo2, roozbeh khosravi rad1∗ 1. emergency medicine department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency medicine department, sina hospital, tehran university of medical sciences, tehran, iran. received: september 2018; accepted: october 2018; published online: 25 january 2019 abstract: introduction: emergency medicine physicians are constantly under psychological trauma due to encountering critically ill patients, mortality, and violence, which can negatively affect their mental and physical health. the present study was performed with the aim of determining the rate of depression and personality disorders in first-year emergency medicine residents and comparing it with the time they reach the 3rd year. methods: in the present prospective cross-sectional study, emergency medicine residents working in multiple teaching hospitals were included via census method and evaluated regarding the rate of depression and personality disorders using the standard mmpi-2 questionnaire upon admission to the program and graduation and their status regarding the evaluated disorders were compared between the 2 phases of evaluation. results: 99 residents with the mean age of 33.93 ± 5.92 years were evaluated. 85 (85.85%) rated their interest in their discipline as moderate to high. the rates of stress (p = 0.020), anxiety (p < 0.001), and hypomania (p = 0.015) had significantly increased during the 3 years and psychasthenia rate had decreased significantly during this time (p = 0.002). changes in the prevalence of other disorders on the third year compared to the year of admission to emergency medicine program were not significant. conclusion: considering the results of the present study, it seems that paying more attention to mental problems and decreasing environmental stressors of medical residents, especially emergency medicine residents, should be among the priorities of managers and policymakers of this discipline. keywords: depression; anxiety; stress, psychological; internship and residency; emergency medicine cite this article as: rahmati f, safari s, hashemi b, baratloo a, khosravi rad r. prevalence of depression and personality disorders in the beginning and end of emergency medicine residency program; a prospective cross sectional study. arch acad emerg med. 2019; 7(1): e5. 1. introduction a considerable part of each individual’s life is spent in the workplace. environmental factors such as noise, crowding, improper light and sound, human factors like conflict with other individuals, and organizational factors such as work density, improper policy making, injustice and many other factors are among the stressors of workplace. if an individual is not able to effectively cope with these mental pressures, numerous physical, mental, and behavioral side effects will manifest and this will bring about decrease in effectiveness and job dissatisfaction (1). the rate of anxiety in those work∗corresponding author: roozbeh khosravi rad; emergency department, tajrish square, shahrdari avenue, tehran, iran. email: khosravirad@yahoo.com tel: 00989122065315 ing in the field of healthcare is higher than the general population and this is related to long night shifts, low sleeping hours, and high and exhausting workload (2). the emergency department is among the hospital environments with a high tension. physicians and other emergency staff are constantly under psychological trauma due to encountering critically ill patients, mortality, and violence, which can negatively affect their mental and physical health (3). emergency physicians experience a high degree of job burnout throughout their career, this rate has been estimated to be about 49% to 65% in emergency medicine residents (4-6). studies have shown that medical residents experience higher degrees of depression compared to other students (7-11). these facts have received attention from graduate accreditation association and a movement has been initiated for improving physicians’ mental health (12). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rahmati et al. 2 evaluating the health condition of medicine students and evaluating the effects of work environment on their psychological balance seems necessary for better planning and improving the conditions by reducing preventable stressors. therefore, the present study has been performed with the aim of evaluating the rate of depression and personality disorders in first-year emergency medicine residents and comparing it with the time they reach the 3rd year. 2. methods 2.1. study design and setting in the present prospective cross-sectional study, all of the first-year emergency medicine residents of shahid beheshti university of medical sciences, admitted in 2014-2015, were evaluated. the questionnaires used were filled out after obtaining informed consent and by keeping data of the participants completely confidential, once when they entered the program (first year) and once at the time of graduation (third year). the study was approved by the ethics committee of shahid beheshti university of medical sciences. 2.2. participants sampling was done using census method and all of the firstyear residents, working in teaching hospitals affiliated with the mentioned university, were included without any age or sex limitation. not giving consent for participation in the study or dropping out of the program and not filling the questionnaire on the third year were exclusion criteria. 2.3. data gathering the tools used for gathering data in this study were baseline characteristics questionnaire and 71-question mmpi2 questionnaire for evaluating the rate of depression and personality disorders. minnesota multiphasic personality inventory (mmpi) is a standard questionnaire for recalling a broad range of self-described characteristics and scoring them, which gives a quantitative index of the individual’s emotional and their viewpoint on participating in the test (13). all firstyear residents filled out the questionnaires in the first phase of the study and their data were recorded. then 2 years later and in the second phase of the study, the same residents, who had become third-year residents then, filled out the questionnaires again. finally, the data gathered in the first and third year were compared. in addition, important happenings affecting mental health (such as getting married, having babies, losing dear ones, acute problem in the family, acute disease for the residents themselves,. . . ) that had happened during the 2 years (between the 2 phases of the study) were also recorded to eliminate their confounding effect. the person in charge of data gathering was an emergency medicine resident that personally gathered the data on the first and table 1: baseline characteristics of the studied residents variable frequency (%) sex male 43 (43.4) female 56 (56.6) age (year) 25 – 34.9 59 (59.60) 35 – 44.9 34 (34.34) > 45 6 (6.06) marital status married 50 (50.50) single 49 (49.50) household breadwinner yes 29 (29.30) no 70 (70.70) history of consuming tranquilizers yes 24 (24.24) no 75 (75.76) smoking yes 22 (22.22) no 77 (77.78) family history of psychiatric disorders yes 23 (23.23) no 76 (76.77) sports activities low 49 (49.50) moderate 42 (42.42) high 8 (8.08) interest in emergency medicine low 14 (14.15) moderate 41 (41.41) high 44 (44.44) monthly outcome (us dollars) 500 – 1000 37 (37.38) 1000 – 1500 42 (42.42) > 1500 20 (20.20) third year. 2.4. statistical analysis data were analyzed using spss software, version 18. to describe data, mean and standard deviation or frequency and percentage of the variables were used. before-after test was applied for comparing the condition of personality assessment indices on the first and third year. p<0.05 was considered as level of significance. 3. results 99 residents with the mean age of 33.93 ± 5.92 (26 – 55) years were evaluated (56.6% female). table 1 has depicted the baseline characteristics of the studied residents. 85 (85.85%) residents rated their interest in their discipline as moderate to high and only 20 (20.20%) had an income more than 15 million rials (1500 us dollars) a month. table 2 has compared the prevalence of depression and other personality disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e5 table 2: comparing the prevalence of various disorders among the studied residents in their first and third year of emergency medicine residency training disorder no mild moderate severe very severe p depression first year 11 (11.1) 34 (34.3) 42 (42.4) 12 (12.1) 0 (0.0) 0.076 third year 25 (25.3) 27 (27.3) 38 (38.4) 9 (9.1) 0 (0.0) anxiety first year 29 (29.3) 33 (33.3) 28 (28.3) 6 (6.1) 3 (3.0) <0.001 third year 14 (14.1) 19 (19.2) 39 (39.4) 22 (22.2) 5 (5.0) stress first year 29 (29.3) 28 (28.3) 27 (27.3) 8 (8.1) 7 (7.1) 0.020 third year 14 (14.1) 21 (21.2) 36 (36.4) 17 (17.2) 11 (11.1) hypochondriasis first year 6 (6.1) 24 (24.2) 39 (39.4) 28 (28.3) 2 (2.0) 0.074 third year 3 (3.0) 14 (14.1) 45 (45.5) 28 (28.3) 9 (9.1) hysteria first year 13 (13.1) 24 (24.2) 37 (37.4) 24 (24.2) 1 (1.0) 0.113 third year 6 (6.1) 39 (39.4) 29 (29.3) 23 (23.2) 2 (2.0) psychasthenia first year 25 (25.3) 31 (31.3) 22 (22.2) 13 (13.1) 8 (8.1) 0.002 third year 24 (24.2) 39 (39.4) 33 (33.3) 3 (3.0) 0 (0.0) paranoia first year 21 (21.2) 43 (43.4) 16 (16.2) 17 (17.2) 2 (2.0) 0.079 third year 7 (7.1) 48 (48.5) 20 (20.2) 22 (22.2) 2 (2.0) schizophrenia first year 27 (27.3) 39 (39.4) 20 (20.2) 13 (13.1) 0 (0.0) 0.316 third year 18 (18.2) 37 (37.4) 25 (25.3) 19 (19.2) 0 (0.0) hypomania first year 30 (30.3) 49 (49.5) 18 (18.2) 2 (2.0) 0 (0.0) 0.015 third year 13 (13.1) 58 (58.6) 21 (21.2) 7 (7.1) 0 (0.0) orders at the time the mentioned residents were enrolled in the emergency medicine program with their third year (the time of graduation). based on the comparison, stress (p = 0.020), anxiety (p < 0.001), and hypomania (p = 0.015) had significantly increased during the 3 years and psychasthenia rate had decreased significantly during this time (p = 0.002). changes in the prevalence of other disorders on the third year compared to the year of admission to emergency medicine program were not significant. 4. discussion based on the results of the present study, the rate of stress, anxiety and hypomania in the third year emergency medicine residents had significantly increased compared to the time they were first admitted to the residency program and severity of psychasthenia had decreased. changes in the rate of other disorders on the third year compared to the year of admission to emergency medicine program were not significant. considering the nature of their job, physicians and healthcare team members are more exposed to stress and anxiety compared to other people in the society (2). therefore, paying attention to this matter in this group of people is very important. studies that have been carried out in this regard have reported contradicting results regarding the rate of stress that medical staff members bear; some have reported high rates of stress in surgeons (14) and emergency physicians (15), and in some other studies no significant difference was found regarding stress rate in emergency physicians (16). in another study, results showed that the rate of cortisol measured in residents was not related to the year of residency program they were in (17). however, in another study, the level of stress among professors of medicine had a significant increase after a few years passing (18). this finding shows that increase in cortisol production following stress does not significantly drop with gaining experience (17). an increase in the rate of anxiety following increase in the years of residency in residents was another finding of the present study, which is in line with the study by buddebergfischer et al. (19). cabrera et al. (2018) found that emergency medicine residents experience many times more stress and anxiety compared to the general population and this increase in anxiety directly correlates with the increase in their duration of stay and shifts in the emergency department. in this study, no sex difference was observed between the residents regarding anxiety rate (17). overall, it should be noted that in addition to the problems that stress, anxiety, and depresthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rahmati et al. 4 sion as factors of mental health cause for the resident during education, they also lead to interference with their professional role and taking responsibility of the society’s health in the future. therefore, it seems that prevention of stress, anxiety and depression of residents and decreasing their mental pressure can play an important role in increasing their interest in working and protecting people’s health in acute and critical situations and cooperating with the group and feeling responsible. considering the results of the present study, it seems that paying more attention to mental problems of medical residents, especially emergency medicine residents, should be among the priorities of managers and policymakers of this discipline. 5. limitation one of the limitations of the present study is its small sample size, which was also seen in previous studies (15, 20). inability to control some confounding factors such as the menstrual cycle, and personal and family problems were also among the limitations of this study. another important point is that a control group was not available for performing more comparisons. 6. conclusion based on the results of the present study, the rate of stress, anxiety, and hypomania in the third year emergency medicine residents had significantly increased compared to the time they were first admitted to the residency program and severity of psychasthenia had decreased. changes in the rate of other disorders on the third year compared to the year of admission to emergency medicine program were not significant. 7. appendix 7.1. acknowledgements all the residents and teaching staff members of hospitals affiliated with shahid beheshti university of medical sciences are thanked for their cooperation. 7.2. author contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors orcids saeed safari: 0000-0002-7407-1739 behrooz hashemi: 0000-0002-5077-8545 alireza baratloo: 0000-0002-4383-7738 7.3. funding/support none. 7.4. conflict of interest none. references 1. vaziri s, mohammadi f, mosaddegh r, masoumi g, noyani a, bahadormanesh a. prevalence and causes of job burnout syndrome among emergency medicine residents of iran university of medical sciences. iranian journal of emergency medicine. 2016;5(10):1-6. 2. pereira-lima k, loureiro sr. burnout, anxiety, depression, and social skills in medical residents. psychol health med. 2015;20:353-62. 3. vanyo l, sorge r, chen a, lakoff d. posttraumatic stress disorder in emergency medicine residents. annals of emergency medicine. 2017;70(6):898-903. 4. shanafelt td, boone s, tan l, dyrbye ln, sotile w, satele d, et al. burnout and satisfaction with work-life balance among us physicians relative to the general us population. archives of internal medicine. 2012;172(18):137785. 5. lu dw, dresden s, mccloskey c, branzetti j, gisondi ma. impact of burnout on self-reported patient care among emergency physicians. western journal of emergency medicine. 2015;16(7):996. 6. kimo t, ramoska e, clark t, al. e. factors associated with burnout during emergency medicine residency. acad emerg med. 2014;21:1031-5. 7. schneider se, phillips wm. depression and anxiety in medical, surgical, and pediatric interns. psychological reports. 1993;72(3_suppl):1145-6. 8. kessler rc, berglund p, demler o, jin r, merikangas kr, walters ee. lifetime prevalence and age-of-onset distributions of dsm-iv disorders in the national comorbidity survey replication. archives of general psychiatry. 2005;62(6):593-602. 9. dyrbye ln, thomas mr, shanafelt td. systematic review of depression, anxiety, and other indicators of psychological distress among us and canadian medical students. academic medicine. 2006;81(4):354-73. 10. sen s, kranzler hr, krystal jh, speller h, chan g, gelernter j, et al. a prospective cohort study investigating factors associated with depression during medical internship. archives of general psychiatry. 2010;67(6):557-65. 11. joules n, williams dm, thompson aw. depression in resident physicians: a systematic review. open journal of depression. 2014;3(03):89. 12. daskivich tj, jardine da, tseng j, correa r, stagg bc, jacob km, et al. promotion of wellness and mental health this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e5 awareness among physicians in training: perspective of a national, multispecialty panel of residents and fellows. journal of graduate medical education. 2015;7(1):143-7. 13. butcher jn. minnesota multiphasic personality inventory. the corsini encyclopedia of psychology. 2010:1-3. 14. alobid i, de pablo j, mullol j, centellas s, parramon g, carrasco j, et al. increased cardiovascular and anxiety outcomes but not endocrine biomarkers of stress during performance of endoscopic sinus surgery: a pilot study among novice surgeons. archives of otolaryngology– head & neck surgery. 2011;137(5):487-92. 15. cabrera jg, prada mf, ruano rm, blazquez a, solvas jg, peinado jm. psychosocial risk at work, selfperceived stress, and salivary cortisol level in a sample of emergency physicians in granada. emergencias. 2012;24(2):101-6. 16. nakajima y, takahashi t, shetty v, yamaguchi m. patterns of salivary cortisol levels can manifest work stress in emergency care providers. the journal of physiological sciences. 2012;62(3):191-7. 17. gonzalez-cabrera jm, fernandez-prada m, iribar c, molina-ruano r, salinero-bachiller m, peinado jm. acute stress and anxiety in medical residents on the emergency department duty. international journal of environmental research and public health. 2018;15(3):506. 18. ritvanen t, louhevaara v, helin p, vaisanen s, hanninen o. responses of the autonomic nervous system during periods of perceived high and low work stress in younger and older female teachers. applied ergonomics. 2006;37(3):311-8. 19. buddeberg-fischer b, stamm m, buddeberg c, klaghofer r. anxiety and depression in residents-results of a swiss longitudinal study. zeitschrift fur psychosomatische medizin und psychotherapie. 2009;55(1):37-50. 20. taylor mk, reis jp, sausen kp, padilla ga, markham ae, potterat eg, et al. trait anxiety and salivary cortisol during free living and military stress. aviation, space, and environmental medicine. 2008;79(2):129-35. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 168 emergency (2015); 3 (4): 168-169 photo quiz a 78-year-old woman with fecaloid vaginal discharge yuh-feng tsai1, wei-yu chen2, chung-fang chiao3, tzong-luen wang4,5, aming chor-ming lin3,4,5* 1. department of diagnostic radiology, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. division of infectious diseases, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. department of intensive care unit, shin kong wu ho-su memorial hospital, taipei, taiwan. 4. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 5. school of medicine, fu-jen catholic university, new taipei city, taiwan. *corresponding author: aming chor-ming lin; emergency department, shin kong wu ho-su memorial hospital, 95 wen chang rd, taipei 111, taiwan. tel: +886-02-28332211 ext 2082; fax: +886-02-28353547; e-mail: m002001@ms.skh.org.tw received: april 2015; accepted: june 2015 figure 1: coronal view of patient’s abdominopelvic computed tomography. figure 2: axial view of patient’s abdominopelvic computed tomography. case presentation: 78-year-old woman with a history of colon cancer with metastasis to the liver was presented to our emergency department because of bilateral groin pain and difficulty in walking, which had gradually increased during the previous 5 days. the pain was of sudden onset, radiating to the back, without aggravating or relieving factors. it was associated with constipation, dysuria and vaginal discharge. she reported passing fecal matter from the vagina one month ago. on physical examination, she appeared malnourished. her blood pressure was 98/65 mmhg, with a 108 beats/min heart rate and 28 breaths/min respiratory rate. she was afebrile. physical examinations were unremarkable, except for pale conjunctiva, abdominal distention, and diffuse tenderness especially over the umbilicus with guarding tenderness. bowel sounds were decreased. pelvic examination showed a yellowish odorous vaginal discharge from the external orifice of uterus. a complete blood cell count showed the following: leukocyte count, 34,200/mm3; segmented neutrophils, 87.5%; hemoglobin level of 7.4 mg/dl; hematocrit, 18.8%; and platelet, 180000/ul. other laboratory studies included: glucose, 86 mg/dl; serum urea nitrogen, 28 mg/dl; serum creatinine, 0.87 mg/dl; sodium, 142 meq/l; potassium, 4.8 meq/l; albumin, 2.5g/dl; a carbohydrate antigen 19-9 level of 3,244 u/ml, and a carcinoembryonic antigen (cea) level of 64.6 ng/ml. coronal and axial cuts of patient’s abdominopelvic computed tomography (ct) are shown in figures 1 and 2. what is your diagnosis? a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 169 tsai et al diagnosis: ct of the abdomen and pelvis showed severely distended uterine containing air bubble and fecal material that were consistent with diagnosis of colouterine fistula. case fate: considering the patient’s malignancy, associated comorbidities, and lack of signs of peritonitis, the patient denied colostomy. she was kept fasting and started on partial parenteral nutrition and intravenous antibiotics. she was admitted with plans for hospice care and died 12 days later. discussion: colon cancer associated fistula formation is a relatively rare complication. the most common type of fistula is a colovesical fistula followed by a colovaginal fistula arising from the sigmoid colon (1, 2). colouterine fistula formation secondary to colon cancer is an extremely rare complication because of the uterus being a thick muscular organ. a colouterine fistula was first reported by lejemtel in 1909 (3). three main etiologies including uterine trauma, presence of abscess rupture into the bowel and the uterus, and uterine or sigmoid carcinoma have been described. a colouterine fistula might be caused by the spontaneous rupture of a gravid uterus, uterine or sigmoid colon cancer, radiotherapy, polymyomectomy, and foreign body (4-6). diverticulitis or malignancy of the sigmoid colon can present as pyometra. clinical manifestations of colovaginal and colouterine fistulas may be similar (7). colon cancer may invade the uterine with subsequent abscess formation that results in colouterine fistula formation. fistula formation by colonic cancer occurs when a tumor extends or ruptures into an adjacent organ such as bladder, small bowel or vagina (8, 9). ct is routinely performed for diagnosis in patients with a suspected colouterine fistula. in a colouterine fistula, air bubbles in the uterine cavity and colon wall joined to the uterus may be identified in ct findings (7). colouterine fistula secondary to sigmoid cancer is a very rare condition. colouterine fistula can present with malodorous vaginal discharge. acute abdomen is now most commonly evaluated by ct in the emergency department. the diagnosis is easily made with clinical history and abdominopelvic ct scan, which reveal the presence of an extraluminal gas collection within the uterine (4, 9). conclusion: fecal vaginal discharge may be indicative of a colouterine or a colovaginal fistula. patients often present with passage of gas, malodorous fecal or purulent vaginal discharge for days or months. diagnosis depends on a high index of suspicion. it should be suspected in any patient with a persistent vaginal discharge. acknowledgments: we would like to express our special thanks to shin kong wu ho-su memorial hospital staff. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. woods rj, lavery ic, fazio vw, jagelman dg, weakley fl. internal fistulas in diverticular disease. dis colon rectum. 1988;31(8):591-6. 2. foulatier o, verspyck e, roman h, scotté m. colouterine fistula complicating diverticulitis: a case report and review of the literature. eur j obstetr gynecol reproduct biol. 2003;110(1):107-10. 3. chaikof el, cambria rp, warshaw al. colouterine fistula secondary to diverticulitis. dis colon rectum. 1985;28(5):35860. 4. halevy a, bracha m, jeroukhimov i, schneider d, nesterenko v. en bloc resection for malignant colouterine fistula. tech coloproctol. 2010;14(1):37-9. 5. uzan j, koskas m, fournier p, margulies al, luton d, yazbeck c. colouterine fistula after polymyomectomy: a case report. j med case reports. 2014;8(1):199. 6. islam a, arif s. colouterine fistula with a foreign body. j ayub med coll abbottabad. 2010;22(2):205-7. 7. blumetti j, harrison j, abcarian h. diverticular fistulas to the female reproductive tract: colouterine and colosalpingoovarian fistulas. am surg. 2015;81(2):e50-1. 8. kiani qh, george ml, carapeti ea, schizas am, williams ab. colovesical fistula: should it be considered a single disease? ann coloproctol. 2015;31(2):57-62. 9. shimamura t, kokuba y, yube y, et al. sigmoid colon diverticulosis with stenosis: case report and review of the japanese literature. j st marianna uni. 2014;5(2):117-24. case presentation: what is your diagnosis? case fate: discussion: conclusion: acknowledgments: conflict of interest: funding support: authors’ contributions: references: archives of academic emergency medicine. 2020; 8(1): e51 rev i ew art i c l e management of pemphigus in covid-19 pandemic era; a review article fahimeh abdollahimajd1, mohammad shahidi-dadras1, reza m robati1,2∗, sahar dadkhahfar1 † 1. skin research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of dermatology, loghman hakim hospital, shahid beheshti of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 18 april 2020 abstract: the novel coronavirus is rapidly spreading around the world. since the public announcement of the covid-19 outbreak, several concerns have been raised by dermatologists as well as pemphigus patients who take immunosuppressive drugs. in this paper, we review the literature about the common treatment of pemphigus with a focus on the lessons from similar epidemics to find a proper suggestion to manage pemphigus in the covid19 pandemic era. the effect of many of the drugs used for treatment of pemphigus vulgaris (pv ) on covid-19 is not clear. we also do not have data on the impact of this autoimmune disease, which may involve the mucous membranes, on the acquisition or course of covid-19. we are currently in the midst of a pandemic and evaluating the effect of covid-19 on the population of susceptible patients suffering from auto-immune diseases like pemphigus is essential. the evidence on best ways to manage patients with underlying conditions, such as pemphigus, during the outbreak of covid-19 is evolving and the data is updated every day. keywords: covid-19; pemphigus; severe acute respiratory syndrome coronavirus 2; therapy cite this article as: abdollahimajd f, shahidi-dadras m, m robati r, dadkhahfar s. management of pemphigus in covid-19 pandemic era; a review article. arch acad emerg mede. 2020; 8(1): e51. 1. introduction the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [sars-cov-2]) is spreading around the world and has caused a pneumonia outbreak originating in wuhan, china. the disease was later named coronavirus disease 2019 (covid-19) in february 2020, by who (1). the epidemiological and clinical characteristics of patients, as well as risk factors for mortality and clinical course of illness have been illustrated (2). according to the current evidence, sars-cov-2 commonly involves individuals aged 30-80 years and has low mortality in healthy individuals but can be lifethreatening, resulting in severe illness and even death due to sepsis, acute respiratory distress syndrome (ards) and multi-organ failure (2). pemphigus vulgaris is a potentially life-threatening autoimmune bullous disease affecting the ∗corresponding author: reza m robati; skin research center, shahid beheshti university of medical sciences, shohada-e tajrish hospital, tehran, iran. tel: +9821 22741507-10, fax: +9821 22744393, email: rmrobati@gmail.com † corresponding author: sahar dadkhahfar; skin research center, shahid beheshti university of medical sciences, tehran, iran. email: sahar.dadkhahfar@gmail.com skin and mucosa and is caused by autoantibodies directed against desmoglein 1 and desmoglein 3 adhesion molecules of the epidermis (3, 4). severe cases of pv represent a true medical emergency (5). since the public announcement of the covid-19 outbreak, several concerns have been raised by dermatologists as well as pemphigus patients who take immunosuppressive drugs. these concerns include the need for proper disease control with minimal immune suppression to avoid possible fatal outcomes. it is also crucial to understand how the underlying mechanisms in covid-19 (e.g. cytokine release storm leading to interstitial pulmonary inflammation, extensive lung damage and acute respiratory distress syndrome) (6) could affect those auto-immune diseases such as pemphigus. in this paper, we review the literature on the common treatments of pemphigus with a focus on lessons from similar epidemics to find a proper suggestion to manage pemphigus in the covid-19 pandemic era. 2. systemic corticosteroids historically, systemic corticosteroids, usually oral prednisone alone or in combination with immunosuppressive drugs, have been used as the mainstay treatment in pemphithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. abdollahimajd et al. 2 gus vulgaris (7). although these agents have led to substantial improvement in the prognosis of the disease, treatment complications, especially the risk of infections, remain major areas of concern (8, 9). when used as pulse therapy, steroids may lead to cardiac side effects (10, 11). this concern becomes even more pronounced during the epidemic of some infectious agents, including the coronavirus. considering the effect of systemic corticosteroids on suppressing inflammation and the presence of lung inflammation induced by host immune responses in influenza, sars-cov, mers-cov, and sars-cov-2 infections, these therapeutic agents have been of interest to physicians during the outbreaks of these infections (2, 12). existing clinical data have not confirmed the beneficial effect of corticosteroids in treatment of respiratory infections due to sars-cov, or mers-cov (12). the observational studies had reported increased mortality and secondary infection rates in influenza, impaired clearance of sars-cov and mers-cov, and complications of corticosteroid therapy (e.g. diabetes, avascular necrosis, and steroidinduced psychosis) in survivors (13, 14). therefore, not only does the role of steroids in the treatment of acute lung injury in these viral infections remain controversial, but also this treatment may be harmful in patients with 2019-ncov infection (12, 15). currently, pandemic-related emotional stress, decreasing the dose of immunosuppressive medications for fear of covid19 and eventually getting this infection may be considered as exacerbating factors or triggers for pemphigus vulgaris (16). therefore, strict adherence to health principles and avoiding emotional stress while continuing the treatment protocol recommended by dermatologists may help prevent exacerbation or recurrence of pemphigus. 3. rituximab rituximab (rtx) is a chimeric monoclonal anti-cd20 antibody that causes depletion of cd20-expressing b cells (17, 18). early treatment with rituximab has resulted in higher remission rates, long term clinical response, lower incidence of serious adverse events and rapid prednisone tapering compared to old immunosuppressive therapies making its approval as a first-line therapy in pemphigus possible (19). rituximab is generally considered safe in patients with pemphigus vulgaris and serious infections, while reported, are rare. although single rtx infusions do not seem to impair memory responses against known pathogens (20), patients may exert a defective immune reaction against new pathogens and life-threatening infections, including sepsis, have been reported following rtx treatment (21). opportunistic infections such as cytomegalovirus infection and pneumocystis pneumonia (pcp), although extremely rare and limited to sporadic case reports, have been reported (22, 23). the risk of reactivation of hepatitis b and c viruses as well as tuberculosis has also been reported (17). it should be noted that protective humoral immunity in the central nervous system (cns) requires peripheral cd19-dependent germinal center formation following neurotrophic coronavirus infection (24) and there are evidence that show sars-cov-2 targets cns (25). although the expression of ace 2 (the host cell-surface receptor for sars-cov-2 envelope spike glycoprotein) in the brain has been proposed, the exact mechanism of cns involvement in covid-19 is not known, yet (25). accordingly, since the characteristic of the immune response against sars-cov-2 has not been identified, the potential risks of treating pemphigus with rituximab should be taken into account. special attention must be paid to close monitoring of the patients and tapering concurrent corticosteroids to minimize susceptibility to life-threatening infections. this risk should be weighed against the prominent and effective role of rtx in treatment of pemphigus and reducing the number of follow up visits (19). 4. other immunosuppressive agents most guidelines suggest azathioprine (aza) or mycophenolate mofetil (mmf) as first-line steroid-sparing agents for treatment of pemphigus rather than other adjuvant immunosuppressants (18). nevertheless, different variables such as age and comorbidities of the patients, dermatologist’s personal experience and costs need to be considered since other drugs, such as cyclophosphamide, also show efficacy (8). it should be noted that in comparison to corticosteroid alone, these drugs mainly exert a corticosteroidsparing effect that leads to a reduction in the risk of relapse by 29% rather than achieving remission (26). currently, data regarding the administration of these drugs during covd19 are scarce and inconclusive. we recommend that these drugs only be discontinued in proven cases of covid-19. it is noteworthy that there are reports of atypical presentation of middle east respiratory syndrome virus (mers-cov ) in patients who received immunosuppressive drugs; therefore, careful monitoring of patients for atypical symptoms should be taken into account (27). the administration of intravenous immunoglobulin (ivig) is a therapeutic option in patients with severe/refractory pv (28). since ivig might be the safest immunomodulator for long-term use in all age groups (29), treatment with ivig has been proposed as a potential option for covid-19 (6) but data are scarce and controversial. in pemphigus patients with covid-19 and flare of pv, this therapeutic option can be considered but should be weighed against possible side effects such s thromboembolism in severely ill patients (30). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e51 figure 1: the proposed algorithm for management of pemphigus patients during the outbreak of covid-19. off all systemic therapies: the patient has not been taking any systemic therapy for at least 2 months. minimal therapy: the patient has been on maintenance therapy [prednisolone (or the equivalent) ≤ 10mg/d and/or minimal adjuvant therapy and/or topical corticosteroids for at least 2 months). partial remission: there are transient lesions that heal within a week without additional treatment. complete remission: there is no stable or new lesion. relapse: the extension of stable lesion(s) and/or the development of ≥ 3 new lesions per month that do not disappear within 1 week without additional treatment ivig: intravenous immunoglobulin (18). 5. recommendations patients with pemphigus need proper treatment for their underlying condition; however, during the outbreak of covid19, these patients may carry the risk of severe infections with disastrous outcomes. figure 1 is a proposed algorithm for management of patients with pemphigus during the covid19 outbreak based on the former consensus on treatment of pemphigus and the current evidence on covid-19. the following issues should be particularly considered. • clear information should be given to patients and caregivers to avoid panic and mismanagement. • application of teledermatology resources for close follow up and monitoring of the patients to minimize patient’s referral to healthcare centers could be very helpful (31). • patients should be followed at regular intervals with a focus on screening the patients for symptoms of covid-19. • healthcare professionals who are in close contact with these patients should be monitored and be vigilant in using recommended precautions and proper ethical teledermatology practice (31). • psychological tolerance of patients during quarantine, especially in those who receive high doses of corticosteroids leading to mood swings, should be monitored and possible coping strategies should be discussed. • the possible flare of the underlying condition should be seriously considered in cases of drug discontinuation without reasonable indication. • patients with milder disease can be treated less aggressively with local steroids (topical or intralesional), dapsone and doxycycline (7). • if indicated, it is better to administer rtx in an infusion center outside the hospitals that are treating covid-19 patients. • with regard to the current and emerging treatments of covid-19 such as anti-malaria drugs (32) and il6 inhibitors (33), dermatologists have to consider possible drug interactions or more rigorous prophylactic strategies in pv patients, respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. abdollahimajd et al. 4 6. conclusion we are currently in the midst of a pandemic and evaluating the effect of covid-19 on the population of susceptible patients suffering from auto-immune diseases like pemphigus is essential. many patients with pv may present to emergency rooms needing emergent care. the effect of many of the drugs used for treatment of pemphigus vulgaris (pv ) on covid-19 is not clear. we also do not have data on the impact of this autoimmune disease, which may involve the mucous membranes, on the acquisition or course of covid-19. despite these limitations, the evidence on best ways to manage patients with underlying conditions, such as pemphigus, during the outbreak of covid19 is evolving and the data is updated every day. we hope the issues brought up by this paper can help physicians to make the best decisions for their patients. 7. declarations 7.1. acknowledgements none 7.2. authors contributions f.a, m.s, r.m.r, and s.d contributed to the idea, design and implementation of this review article, and to the writing of the manuscript. all the authors approved the final submitted version of this manuscript. authors orcids fahimeh abdollahimajd: 0000-0002-9463-0665 mohammad shahidi-dadras: 0000-0001-7789-1997 reza m robati: 0000-0002-7947-8642 sahar dadkhahfar: 0000-0003-4058-2562 7.3. funding support none. 7.4. conflict of interest none. references 1. velavan tp, meyer cg. the covid-19 epidemic. trop med int health. 2020;25(3):278-80. 2. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. lancet. 2020; pii: s0140-6736(20)30566-3. 3. stanley jr, amagai m. pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome. n eng j med. 2006;355(17):1800-10. 4. wu h, wang zh, yan a, lyle s, fakharzadeh s, wahl jk, et al. protection against pemphigus foliaceus by desmoglein 3 in neonates. n eng j med. 2000;343(1):31-5. 5. kridin k, zelber-sagi s, bergman r. pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. act derm venereol. 2017;97(8-9):1095-9. 6. wang ls, wang yr, ye dw, liu qq. a review of the 2019 novel coronavirus (covid-19) based on current evidence. int j antimicrob agents. 2020:105948. 7. zhao cy, murrell df. pemphigus vulgaris: an evidencebased treatment update. drugs. 2015;75(3):271-84. 8. gheisari m, faraji z, dadras ms, nasiri s, robati rm, moravvej h, et al. methylprednisolone pulse therapy plus adjuvant therapy for pemphigus vulgaris: an analysis of 10 years’ experience on 312 patients. dermatol ther. 2019;32(5):e13057. 9. kunisaki km, janoff en. influenza in immunosuppressed populations: a review of infection 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hebert v, houivet e, calbo s, et al. first-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. lancet. 2017;389(10083):2031-40. 20. cho a, bradley b, kauffman r, priyamvada l, kovalenkov y, feldman r, et al. robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab. jci insight. 2017;2(12). pii: 93222. 21. kasperkiewicz m, eming r, behzad m, hunzelmann n, meurer m, schulze-koops h, et al. efficacy and safety of rituximab in pemphigus: experience of the german registry of autoimmune diseases. j dtsch dermatol ges. 2012;10(10):727-33. 22. chiu h-y, chang c-y, hsiao c-h, wang l-f. concurrent cytomegalovirus and herpes simplex virus infection in pemphigus vulgaris treated with rituximab and prednisolone. acta derm venereol. 2013;93(2):200-1. 23. wei k, wang y, wang w, chen w. fatal infection of pneumocystis jiroveci pneumonia in a pemphigus patient treated with rituximab. j eur acad dermatol venereol. 2017;31(8): e350-e351. 24. atkinson jr, bergmann cc. protective humoral immunity in the central nervous system requires peripheral cd19-dependent germinal center formation following coronavirus encephalomyelitis. j virol. 2017;91(23):e01352-17. 25. baig am, khaleeq a, ali u, syeda h. evidence of the covid-19 virus targeting the cns: tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. acs chem neurosci. 2020; 11(7):995-998. 26. atzmony l, hodak e, leshem ya, rosenbaum o, gdalevich m, anhalt gj, et al. the role of adjuvant therapy in pemphigus: a systematic review and meta-analysis. j am acad dermatol. 2015;73(2):264-71. 27. kim s-h, ko j-h, park ge, cho sy, ha ye, kang jm, et al. atypical presentations of mers-cov infection in immunocompromised hosts. j infect chem. 2017;23(11):769-73. 28. brown ae, motaparthi k, hsu s. rituximab and intravenous immunoglobulin as alternatives to long-term systemic corticosteroids in the treatment of pemphigus: a single center case series of 63 patients. dermatol online j. 2018;23(12). 29. zhang l, liu y. potential interventions for novel coronavirus in china: a systematic review. j med virol. 2020;92(5):479-90. 30. lew tw, kwek t-k, tai d, earnest a, loo s, singh k, et al. acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. jama. 2003;290(3):374-80. 31. pathoulas jt, stoff bk, lee kc, farah rs. ethical outpatient dermatology care during the coronavirus (covid-19) pandemic. j am acad dermatol. 2020 may;82(5):1272-1273. 32. devaux ca, rolain j-m, colson p, raoult d. new insights on the antiviral effects of chloroquine against coronavirus: what to expect for covid-19? int j antimicrob agents. 2020 mar 12:105938. 33. mehta p, mcauley df, brown m, sanchez e, tattersall rs, manson jj. covid-19: consider cytokine storm syndromes and immunosuppression. lancet. 2020; pii: s0140-6736(20)30628-0. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction systemic corticosteroids rituximab other immunosuppressive agents recommendations conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e2 le t t e r to ed i to r the effect of oxygen therapy on oxidative stress index in patients with acute myocardial infarction; a letter to the editor afshin amini1, abbas mahdavipour1∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: september 2018; accepted: october 2018; published online: 1 january 2019 cite this article as: the effect of oxygen therapy on oxidative stress index in patients with acute myocardial infarction; a letter to the editor. arch acad emerg med. 2019; 7(1): e2. tissue hypoxia is a key factor for cell death after acute myocardial infarction (mi). it seems that increase in the relative oxygen pressure in inhaled air can be an effective treatment option for treating acute mi. however, contradicting findings and results have been published regarding using oxygen therapy in patients with acute mi (1, 2). some researchers have believed that generation of free radicals, induction of oxidative stress, and damage to cell membrane are among side effects of o2 consumption (3, 4). it has been shown that o2 therapy can increase microvascular resistance, result in a decrease in coronary blood flow and cardiac output, and bring about numerous negative effects such as increase in the risk of arrhythmia and cellular damage (4). in aerobic biological systems, defense mechanisms have been put in place for fighting free radicals and reactive oxygen species to neutralize or minimize the damaging effects of these invasive factors. some components of the defense system are enzymes such as superoxide dismutase, glutathione peroxidase, catalase, and. . . , which are synthesized in the body; yet, some of the other components of this system such as vitamin e, beta carotene, and etc. should be provided through the diet (5, 6). during reperfusion, hypoxanthine that had aggregated in the ischemia phase, is metabolized into xanthine via xanthine oxidase enzyme and in this process, superoxide radicals are created and changed into hydrogen peroxide (h2o2) or hydroxyl radicals (oh). oxidative damage happens when antioxidant defense consisting of glutathione, and antioxidant enzymes (like superoxide dismutase, glutathione peroxidase, catalase, and. . . ) is broken down (7). it seems that measurement of oxidative stress biomarkers ∗corresponding author: abbas mahdavipour; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989122517412 email: dr.mahdavipoor@gmail.com can be used as an index for evaluating the effect of oxygen therapy in patients with acute mi. therefore, for testing this hypothesis, in a randomized clinical trial, the researchers of the present study studied 90 patients with acute mi, who had presented to the emergency department of imam hossein hospital within less than 12 hours from the initiation of their symptoms. initially venous blood was drawn from all the patients for measuring oxidative stress parameters. then patients were randomly divided into 2 groups using block randomization. the first group was continuously treated with 6 to 8 liters of oxygen per minute via facial mask and without considering blood o2 saturation, and the second group only received oxygen if their arterial blood saturation level dropped to less than 94%. at the end of the 6th hour after hospitalization blood was drawn from all of the patients (for the second time) to assess oxidative stress parameters including total oxidant enzymes. patients with a history of mi, known cardiac and respiratory diseases (such as obstructive pulmonary disease or obstructive sleep apnea), unstable vital signs, endocrine disorders, hematologic abnormalities, autoimmune diseases or malignancies, pregnancy, and those who did not give consent for participation in the study were excluded. the results showed that case and control groups were not significantly different regarding mean age (60.67 ± 9.17 vs. 61.16 ± 7.53 years; p = 0.783), sex (68.9% male vs. 64.4%; p = 0.823), and oxidant level on admission (p = 0.104). oxidant levels in the control (156.41 ±15.94 vs. 141.84 ± 15.80 µmol/l; p <0.0001) and case (150.94 ± 15.69 vs. 142.59 ±15.35 µmol/l; p <0.0001) groups had significantly reduced after 6 hours. however, the oxidative stress indices in the control group that received oxygen selectively had decreased significantly more than the case group (p <0.0001). in 2012, ranchord et al. showed that there is no evidence regarding high oxygen concentrations being beneficial or harmful in comparithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. amini et al. 2 son with titrated oxygen in patients with mi (8). the study by tatarkova et al. showed that normobaric oxygen therapy will be associated with oxidative damage of myocardia and weakening of antioxidant defense (9). observations of the authors of this study showed that the rate of oxidative indices in patients with acute mi who had received oxygen in a titrated manner and only if their arterial blood oxygen saturation had dropped to less than 94% had decreased more. therefore, it seems that oxygen should literally be seen as a drug and should be prescribed for the patients only when necessary and its benefits outnumber its harms. it seems that giving excess oxygen to acute mi patients who have normal spo2 should be avoided. of course, there is need for more comprehensive studies to be able to comment with certainty in this regard. 1. appendix 1.1. acknowledgements the staff members of emergency department of imam hossein hospital are thanked for their cooperation in performance of this study. 1.2. author’s contribution all the authors of this study met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. authors orcids afshin amini: 0000-0001-8928-8212 1.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support all the expenses of this study have been covered by the researchers. references 1. beasley r, weatherall m, aldington s, mchaffie d, robinson g. oxygen therapy in myocardial infarction: an historical perspective. journal of the royal society of medicine. 2007;100(3):130-3. 2. lorgis l, zeller m, dentan g, sicard p, richard c, buffet p, et al. the free oxygen radicals test (fort) to assess circulating oxidative stress in patients with acute myocardial infarction. atherosclerosis. 2010;213(2):616-21. 3. hammond b, hess ml. the oxygen free radical system: potential mediator of myocardial injury. journal of the american college of cardiology. 1985;6(1):215-20. 4. weston c. oxygen therapy in acute myocardial infarction– too much of a good thing? cochrane database of systematic reviews. 2010(6). 5. gill r, tsung a, billiar t. linking oxidative stress to inflammation: toll-like receptors. free radical biology and medicine. 2010;48(9):1121-32. 6. sharma v, shukla rk, saxena n, parmar d, das m, dhawan a. dna damaging potential of zinc oxide nanoparticles in human epidermal cells. toxicology letters. 2009;185(3):211-8. 7. singhal ab, benner t, roccatagliata l, koroshetz wj, schaefer pw, lo eh, et al. a pilot study of normobaric oxygen therapy in acute ischemic stroke. stroke. 2005;36(4):797-802. 8. ranchord am, argyle r, beynon r, perrin k, sharma v, weatherall m, et al. high-concentration versus titrated oxygen therapy in st-elevation myocardial infarction: a pilot randomized controlled trial. american heart journal. 2012;163(2):168-75. 9. tatarkova z, engler i, calkovska a, mokra d, drgova a, kuka s, et al. effect of normobaric oxygen treatment on oxidative stress and enzyme activities in guinea pig heart. general physiology and biophysics. 2012;31(2):179-84. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references archives of academic emergency medicine. 2019; 7 (1):e38 or i g i n a l re s e a rc h factors with the highest impact on road traffic deaths in iran; an ecological study alireza razzaghi1, hamid soori2∗, amir kavousi3, alireza abadi4,5, ardeshir khosravi6 1. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 2. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. 3. safety promotion and injury prevention research center, department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 4. department of community medicine, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 5. social department of health research center, shahid beheshti university of medical sciences, tehran, iran 6. department of statistics and informatics, iranian ministry of health and medical education, tehran, iran. received: april 2019; accepted: june 2019; published online: 16 july 2019 abstract: introduction: the largest proportion of road traffic deaths (rtds) happen in low and middle income countries (lmics). the efforts for decreasing rtds can be successful if there is precise information about its related risk factors. this study aimed to determine economic, population, road, and vehicle factors with the highest impacts on rtds in iran. methods: this is an ecological study, which has been done using covariates including: the population density, economic growth, urbanization, distance traveled (km) in 100 thousand people, the length of urban roads, the length of rural roads and the vehicle per 1000 population for each province of iran in 2015. the covariates considered had been gathered from different sources and to determine which one of the covariates has an effect on rtds, the negative binomial (nb) regression model was used. results: the mean number of rtds per 100000 population was 474 ± 70.59 in 2015. the highest and lowest rates of death belonged to fars and qom provinces, respectively. the results of the univariate model showed the population density as the only covariate of rtds (p=0.001). also, among other covariates, gdp was the only variable with a p-value equal to 0.2. in the multivariate nb model, it was seen that the population density (p=0.001), and gdp (p=0.02) significantly correlated with rtds. for a unit (million rial) increase in the gdp of the province, the number of deaths decreased by as much as 0.0014. in addition, for a unit increase in population density, the number of deaths went up by as much as 30. conclusion: population density and gdp had positive and negative effects on the number of fatal road traffic injuries, respectively. by considering these factors in presentational and controlling programs on road traffic injuries, it is possible to decrease the rtds. keywords: death; accidents, traffic; mortality; multiple trauma cite this article as: razzaghi a, soori h, kavousi a, abadi a, khosravi a. factors with the highest impact on road traffic deaths in iran; an ecological study. arch acad emerg med. 2019; 7(1): e38. 1. introduction road traffic crashes (rtcs) are one of the main causes of death in all ages, especially among the 15-29 year-old people all over the world. the cost of rtcs is approximately 3% of gross domestic product (gdp), which rises to 5% in low and middle income countries (lmics). the increasing trend ∗corresponding author: hamid soori; safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. email: hsoori@yahoo.com,tel: +982122439980 of rtcs is higher among the countries, which experience the rapid growth of population, urbanization, and motorization (1, 2). a high proportion of road traffic deaths (rtds) happen in lmics. there is a rapid increase in income and economic development in lmics, which causes rapid change and motorization. however, the issues of road safety, related infrastructure development, safety improvement of vehicles, and changing the effective policies are not in accordance with economic changes, urbanization, and motorization, which leads to manifestation of many problems related to road safety (1, 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. razzaghi et al. 2 in high-income countries, road safety system has managed well in accordance with motorization and economic growth. in these countries, actions such as developing the safer roads, safer vehicles, and effective road safety management system have led to a significant reduction in rtds (1, 2). according to international reports, for the first time in history, the global urban living population exceeded 50% of the total population in 2007 and it is constantly rising. by 2020, about 70% of the world population will live in urban areas (4). the world is rapidly urbanizing with extensive changes in population, sustainable mobility feature and the effects of intelligent electronic systems on road safety (1, 4). in some countries such as iran, the rate of urbanization is higher than economic growth (5). however, effective efforts have not been made to improve safety in the road network and vehicles, in spite of increasing the number of vehicles and the length of roads (1, 6). so in some provinces in iran, the large number of vehicles and increasing travels in and out of cities make them prone to rtcs (7). in iran, evaluating the condition of road safety, using the road safety development index (rsdi), showed that they are not in a good condition regarding road network safety despite little improvements (8). meanwhile, road network is used for more than 90% of total national shippings in iran (9). it is expected that rtds will impose a heavy cost on communities if effective efforts are not made (10). the governments can make effective efforts to decrease rtcs only if there are valid and reliable data regarding road traffic injuries and deaths (11). in many lmics, there are no accurate epidemiologic data on rtcs. using statistical methods can be helpful for determining the factors affecting injuries or deaths (12, 13). according to global status report on road safety 2018, the estimated rate of road traffic deaths per 100000 populations is 20.5 around the world (1). there is no information on the risk factors of rtd in iran. this study was conducted to determine factors with the highest impacts on rtds in economic, population, urbanization, length of roads, and vehicle per 1000 population categories using count regression models. 2. methods 2.1. study design and setting this is an ecological study, which was carried out with the aim of modeling rtds by studying population density, economic growth, urbanization rate, number of travels, the length of roads, and the number of the vehicles per 1000 population as covariates in all provinces (31 provinces) of iran using the data of 2015. 2.2. data gathering in this study, the considered covariates were gathered from different sources. the statistics of rtds, as a dependent variable in count regression models, were obtained from the ministry of health and medical education (mohme). in iran, registering and collecting the vital data is done by different organizations such as; the national organization for civil registration (nocr) (as the governmental system that records the vital events), the iranian forensic medicine organization (as a reference point for unnatural deaths), the medical council (as a non-governmental organization for registering all health care professionals), municipalities (as an organization responsible for cemetery in rural and urban areas), and ministry of health and medical education (14). the national reports of world health organization in rtds are prepared by forensic medicine organization (1, 2). however, mohme is the only registration system, which is based on the international classification of disease (icd) standards. according to the findings of a study in 2009 in iran, the coverage rate of mohme registration system is nearly complete (15). the explanatory variables in this study included: urbanization rate in each province (percent), road length (km), gross domestic product (gdp) (as an economic factor), population density, the number of vehicles per 1000 population, and the distance traveled per 100000 population (km). iran is subdivided into thirty-one provinces and all data were in the province level. the gdp information of each province was obtained from tehran chamber of commerce, industries, and agriculture in 2011 (16). the population of provinces and their urbanization rate were gathered from population census, which has done by the statistical center of iran (17). the distance (km) traveled per 100000 population by different vehicles was obtained from the information technology office at the ministry of road and transportation (9). the number of registered vehicles was obtained from the law enforcement force of iran, statistical office (18). the length of road data in each province was obtained from the statistical center of iran, the transportation sector statistic (17). 2.3. statistical analysis at first, the poisson distribution was assessed. in the poisson model, the mean and the variance should be equal. an overdispersion in data was found using test of over-dispersion parameter alpha by running the same model using negative binomial distribution. the parameter alpha value equals to 0.305. this strongly suggests that alpha is non-zero and the negative binomial model is more appropriate than the poisson model (19). the analysis was done in two steps using univariate and multivariate models. the variables with a p-value of less than 0.2 in univariate analysis, entered the multivarithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1):e38 ate regression model (20). finally, factors affecting rtds and their effect sizes were identified. stata software, edition 14, was used for analyzing the data. 3. results the results of the study showed that the mean number of rtds per 100000 population was 474 ± 70.59 in 2015. the highest and lowest rates of death per 100000 population according to poisson model were related to fars and qom provinces, respectively. the highest rate of gdp belonged to tehran, khuzestan, isfahan, and razavi khorasan provinces. the highest and lowest traveled distances per 100000 people (km) were seen in ilam and qazvin provinces, respectively. the population density was highest in tehran and lowest in kohgiluyeh and boyer-ahmad provinces. the overall urbanization rate in the country (all provinces) was 69.76%. qom, tehran, and alborz had the highest rates of urbanization, respectively. also, the lowest rates of urbanization were seen in sistan and baluchestan, golestan, and hormozgan provinces. the highest number of vehicles per 1000 people was observed in tehran and the lowest in sistan and baluchestan. the longest rural roads belonged to fars, khuzestan, and razavi khorasan, respectively. also, the shortest rural roads belonged to qom, alborz, and ilam, respectively. about the urban and suburban regions, the highest roads belonged to sistan and baluchestan, fars, and khorasan razavi, respectively (table 1). the results of univariate analysis using negative binomial model is shown in table 2. the results of the univariate model showed population density as the only covariate of rtds (p=0.001). also, among other covariates, gdp was the only variable with a p-value equal to 0.2. so, population density and gdp were the covariates selected to enter multivariate negative binomial model. in the multivariate nb model, it was seen that population density (p=0.001), and gdp (p=0.02) both significantly correlated with rtds (table 3). the value of the β parameter for gdp was equal to 0.0014. in other words, for a unit (million rial) increase in the gdp of the province, the number of deaths decreases by as much as 0.0014. also, the value of the β parameter for the population density was equal to 30.48. this value means that, for a unit increase in population density, the number of deaths rises by as much as 30. 4. discussion the findings of nb model showed that the effects of population density and gdp on rtd were statistically significant. population is one of the factors affecting rtds. in the global status report on road safety (gsrrs) in 2018, the mortality of rtcs was estimated using nb model. in this report, the covariate of population was introduced as an effective factor in rtcs (1). some issues emerged following population growth such as: high density of population in cities (21), increase in the number of vehicles, changes in the population demographics, and changes in transportation (22). in lmics, there is rapid growth in urban areas regardless of related infrastructure and facilities. this issue leads to manifestation of some road traffic related problems including: property damage, injuries, and deaths (23, 24). in iran, the population has been growing in recent decades and there has been an extensive migration from rural areas to urban areas (7). it should be noted that population growth does not cause an increase in rtcs and their related deaths in all countries. according to gsrrs of who in 2018, the number of deaths in germany (with a population of 81914672), which has a population similar to iran (with a population of 77447169), was about one fifth compared to iran (3206 versus 15932) in 2016 (1). therefore, germany and iran have a similar population, but the number of deaths is not the same. one of the reasons for this difference is discrepancy between rapid growth of population and capacity building in the transportation system (21)(25). while in many high-income countries, the increase in population has been followed by effective changes in the transportation system. for example, the increasing trend of the population has caused the shift from private motorized transport to public transport, or has led to making the infrastructure for cycling or walking instead of using a motorized vehicle. moreover, the rapid changes in vehicle technologies and their improvement by applying intelligent systems have caused improvement in the safety and prevention of crashes and related deaths (26). along with population growth, there are some changes in demographic characteristics. for example, in many countries the elderly population has an increasing trend. according to who report in 2015, the proportion of elderly people in iran (people 60 years or above) will double during 2015-2030 (27). the findings of other studies show that the most important injury among the elderly people is road traffic injuries, which has the highest incidence, death rate and disability adjusted life years (daly) among them (28). gdp (as an economic factor) was the second factor affecting rtds in this study. most studies in this area have used economic indicators such as gdp (29). it was shown that with a raise in gdp, the number of deaths has decreased in provinces. the findings of earlier studies showed that road traffic deaths will increase with launch of development. the rate of rtds will begin to decrease when exceeding a threshold level in economic status (30, 31). in the early stages, economic growth leads to an increase in vehicles and this condition leads to increase in their related injuries and deaths. this is more important for lmics, which are mostly in the early stages of economic developing. the findings of a study in 1975-1988 showed that the rate of road traffic deaths in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. razzaghi et al. 4 table 1: distribution of the studied variables among provinces province gdp (million rials) traveling (km) per 100000 population population density (2015) urbanization rate (percent) number of rtd rtd rate per 100000 population (adjusted) vehicle per 1000 population rural roads (km) urban and suburban roads (km) country 6225659738 59.55 1.00 69.76 14716 19.22 east azerbaijan 207139439 42.61 0.0490 71.9 1007 26.26 10.96 6203 3464 west azerbaijan 125717289 42.70 0.0408 65.4 727 22.42 12.42 5107 2948 ardabil 57913670 58.29 0.0160 68.2 179 13.92 11.21 3711 1599 isfahan 85400000 71.83 0.0642 88 723 14.31 21.06 4517 5414 alborz 416864342 43.01 0.0335 92.6 252 9.71 3.95 907 393 ilam 67161398 214.08 0.0072 68.1 155 26.67 14.41 1425 1482 bushehr 212663477 66.10 0.0143 71.9 309 27.51 27.63 1894 2121 tehran 1436431500 69.59 0.1652 93.9 233 11.83 34.37 1589 983 chaharmahal and bakhtiari 40099640 55.87 0.0118 64.1 182 19.50 13.95 1667 1296 south khorasan 28958350 116.42 0.0096 59 198 25.74 11.86 6686 4455 razavi khorasan 331292272 97.58 0.0803 73.1 1598 25.15 19.60 7044 6412 north khorasan 34956332 59.83 0.0109 56.1 190 20.90 16.11 2322 1359 khuzestan 836240240 40.66 0.0592 75.5 822 17.16 20.23 8477 5276 zanjan 52830070 34.12 0.0132 67.3 207 19.56 14.03 3590 1658 semnan 55759341 58.66 0.0087 79.8 161 23.92 15.25 1434 1600 sistan and baluchestan 75230327 63.88 0.0345 48.5 741 26.54 9.69 7401 8010 fars 262027801 69.99 0.0607 70.1 1608 33.62 22.20 8522 7430 qazvin 84992827 30.42 0.0159 74.8 261 20.88 13.93 3239 1341 qom 59519554 56.05 0.0159 95.2 54 4.37 18.91 703 678 kurdistan 60784463 44.87 0.0200 70.8 428 27.88 9.83 4218 1819 kerman 164052960 40.58 0.0395 58.7 852 27.33 16.67 6494 5692 kermanshah 106086048 51.30 0.0247 75.2 484 24.48 11.49 4364 2841 kohgiluyeh and boyerahmad 143413674 31.90 0.0088 55.7 116 16.50 11.31 2868 1512 golestan 70512931 48.59 0.0234 53.3 444 23.33 16.06 3103 1231 gilan 126890610 42.69 0.0319 63.3 355 13.95 13.27 6445 1891 lorestan 70281385 50.54 0.0222 64.5 360 19.82 14.41 5177 1856 mazandaran 202791471 33.23 0.0410 57.8 773 24.29 14.86 4769 2332 markazi 125424307 42.35 0.0180 76.9 270 18.36 16.03 3608 1845 hormozgan 132781740 43.74 0.0219 54.7 420 24.56 23.06 5341 2897 hamadan 88881887 61.07 0.0220 63.1 433 24.12 16.01 2991 2036 yazd 108536644 63.60 0.0140 85.3 174 15.97 31.04 2580 2295 rtd: road traffic deaths malaysia and colombia had increased; yet, it had decreased in high-income countries by as much as 25-50% (32). the results of a study in brazil in 2008 showed that in the previous decade the north and north-east areas with low gdp had higher rates of death in comparison with other areas with high gdp (33). in iran, the high rate of road traffic deaths correlates with the number of vehicles. the number of vehicles has raised following economic growth, which is in its early stage in iran (5). according to reports of statistical center of iran, the rate of motorization (the number of vehicles per 1000 population) was higher than the economic growth rate during the years 1971-2009 (5). in low and middle-income countries, failure to balance economic growth with the motorization can play a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1):e38 table 2: the results of univariate analysis using the negative binomial regression model variables coefficient se p-value 95% ci low upper population ratio 22.06 5.45 0.001 11.37 32.75 urbanization ratio -0.01 0.012 0.3 -0.034 0.013 gross domestic product 0.0007 0.00077 0.2 -0.0006 0.002 vehicle1 0.013 0.024 0.5 -0.03 0.06 urban road2 0.0002 0.00004 0.7 -0.03 0.003 rural road3 0.0002 0.00003 0.6 -0.002 0.0003 passenger traveler4 -0.0007 0.005 0.8 -0.01 0.009 1. vehicle per 1000 population, 2 urban road (km) in each province,3 rural road (km) in each province, 4 adjusted per/for population. se: standard error, ci: confidence interval. table 3: the results of multivariate analysis of negative binomial model variables coefficient se p-value 95% ci low upper population ratio 30.48 6.36 0.001 17.48 43.48 gross domestic product -0.0014 0.0006 0.02 -0.0026 -0.00019 constant 4.32 0.19 0.001 4.95 5.70 in alpha -1.18 0.24 alpha 0.305 0.074 se: standard error, ci: confidence interval. role in increasing the incidence of road traffic crashes. however, in iran the rate of road traffic deaths has had a decreasing trend in 2007-2018 (34). so the decreasing effect of gdp on rtcs can be explained considering that economic growth has led to an improvement in road safety and raise in investment in transport infrastructure and this has ultimately led to a reduction in rtds (5, 35). 5. strengths and limitations one of the strengths of this study is that it was implemented at the national level and included provincial comparison. on the other hand, this is an ecological study and this should be noted in the interpretation of results. in an ecological study, the ecological inference fallacy occurs if this will not be considered in the interpretation of ecological level data to the individual level. one of the limitations of this study could be the possible information bias in rtd data obtained from the mohme. 6. conclusion the covariate population density increases the fatal road traffic injuries and gross domestic production decreases that. by considering these factors in presentational and controlling programs done on road traffic injuries, it is possible to further decrease road traffic deaths. 7. appendix 7.1. acknowledgements all the people who helped us in collection of the required data are thanked for their cooperation. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids alireza razzaghi: 0000-0003-1874-6364 hamid soori: 0000-0002-3775-1831 amir kavousi: 0000-0003-3922-0564 ardeshir khosravi: 0000-0003-2963-0674 7.3. funding/support this article is derived from a phd thesis funded by shahid beheshti university of medical sciences and iran national science foundation (insf). 7.4. conflict of interest the authors declare that there is no conflict of interest regarding the present study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. razzaghi et al. 6 references 1. world health organization. global status report on road safety 2018. geneva, switzerland. 2. world health organization. global status report on road safety 2015. geneva, switzerland. 3. road deaths and injuries hold back economic growth in developing countries: the world bank2018. 4. city bl, assessment e. urbanization and health. bulletin of the world health organization. 2010;88(4):245-6. 5. mehrgan n, gholizadeh a, mohammadi f. road traffic accident in a economic analysis[persian]. transportation engenering. 2012;4:59-69. 6. world health organization. data systems: a road safety manual for decision-makers and practitioners. geneva, switzerland.2010. 7. seifdini f, mansourian h, pour-ahmad a, darvishzadeh r. processes and patterns of urbanization in iran [persian]. urban and regional studies and research. 2014;6(21):61-84. 8. jafari mr, vosoughi s, abadi m, khandan m. comparing road safety conditions in iran with ten southeast asian countries using road safety index. iran occupational health. 2017;14(5):118-29. 9. road transportation and road organization of the country; iran [persian]: ministry of road and transportation. information technology office2015. 10. zhang x, hongyan y, guoqing h, mengjing c, yue g, xiang h. basic characteristics of road traffic deaths in china. iranian journal of public health. 2013;42(1):7. 11. bhalla k, sharaz s, abraham j, bartels d, yeh p-h. road injuries in 18 countries: methods, data sources and estimates of the national incidence of road injuries. 2011. 12. mohan d. accidental death and disability in india: a stocktaking. accident analysis & prevention. 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trv, guo y, bishai d, pechansky f, team tvnte. road traffic deaths in brazil: rising trends in pedestrian and motorcycle occupant deaths. traffic injury prevention. 2012;13(sup1):11-6. 34. statistical report of road traffic deaths. iranian legal medicine organization; 2018; available from: http://en.lmo.ir/. 35. van beeck ef, borsboom gj, mackenbach jp. economic this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1):e38 development and traffic accident mortality in the industrialized world, 1962–1990. international journal of epidemiology. 2000;29(3):503-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion strengths and limitations conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e26 or i g i n a l re s e a rc h association of admission blood glucose level with major adverse cardiac events in acute coronary syndrome; a cohort study mostafa alavi-moghaddam1, mohammad parsa-mahjoob2, robabeh ghodssi-ghassemabadi3, bita bitazar1∗ 1. emergency medicine department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. cardiovascular research center, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. department of biostatistics, faculty of medical sciences, tarbiat modares university, tehran, iran. received: january 2019; accepted: march 2019; published online: 16 april 2019 abstract: introduction: appropriate management of abnormal admission blood glucose level (abgl) in acute coronary syndrome (acs) patients still remains a common issue. this study aims to assess the influence of abgl on development of 30-day major adverse cardiac events (maces) in patients with suspected acs. methods: this is a prospective cohort study based on analysis of data collected from patients suspected to acute coronary syndrome admitted to emergency department. abgl of patients was measured and its association with development of maces (mi, cva, mortality) within 30 days of follow-up was studied. results: 814 participants with the mean age of 61.8±13.4 years were studied (58.1% male). mace endpoints were developed in 166 (39.0%) hyperglycemic, 30 (46.9%) hypoglycemic, and 53 (16.4%) normoglycemic patients (p<0.001). mean admission blood glucose level of patients who developed mace within 30 days was significantly higher than others (210.6±123.4 vs 157.4±86.6mg/dl; p<0.001; or: 1.006 (1.005 to 1.008)). there was a significant correlation between male gender (p=0.027), abnormal admission blood glucose level (p<0.001), diabetes (p = 0.001), hyperlipidemia (p=0.059), prior cabg (p=0.008), first and second blood troponin levels (p<0.001), first and second abnormal ecgs (p<0.001), and also ecg changes (p<0.001) with developing mace. abnormal abgl, first and second blood troponin levels, and the history of diabetes were among independent risk factors of developing mace within 30 days. conclusion: it seems that abnormal admission blood glucose level in suspected acs patients was an independent predictor of major adverse cardiac events within 30 days. keywords: blood glucose; acute coronary syndrome; myocardial infarction; stroke; death cite this article as: alavi-moghaddam m, parsa-mahjoob m, ghodssi-ghassemabadi r, bitazar b. association of admission blood glucose level with major adverse cardiac events in acute coronary syndrome; a cohort study. arch acad emerg med. 2019; 7(1): e26. 1. introduction associations between elevated admission blood glucose level (abgl) and bigger infarct size in acute myocardial infarction (ami) as well as inflammation in acute coronary syndrome (acs) have been reported (1, 2). many studies have argued about the possible direct impact of hyperglycemia on adverse outcomes of acute coronary syndrome patients through various pathophysiological mechanisms. recent studies have suggested that hyperglycemia has a detrimental effect on is∗corresponding author: bita bitazar; emergency medicine department, imam hossein hospital, madani avenue, imam hossein square, tehran, iran. email: md.bitazar@gmail.com tel: +9821-77558001 chemic myocardium. it has been reported that acute hyperglycemia abolishes ischemic preconditioning and promotes apoptosis (3, 4). acute hyperglycemia also decreases nitric oxide bioavailability, impairs endothelial function, increases platelet aggregability and stimulates coagulation (5). these changes may cause microvascular dysfunction during reperfusion and impaired left ventricular function after ami (6). this theory has a measure of support from studies that have identified a stronger correlation between the risk of acs in patients with hyperglycemia without a history of diabetes (7). there is a biological plausibility to this result as these patients may have an undiagnosed, untreated diabetic state resulting in more glycolytic damage than someone known to have diabetes and actively receiving treatment. similar findings were obtained by petursson et al. when assessing 30-day this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. alavi-moghaddam et al. 2 mortality risk of patients with confirmed acs (8). this result has also been reported in patients experiencing ami (9). some studies have suggested insulin administration in patients with severe hyperglycemia at the time of admission in emergency department regardless of their diabetic state (10, 11). in a guideline published by national health system of the great britain, insulin administration is recommended in patients with confirmed acs with admission blood glucose level higher than 198 mg/dl (12). in a japanese study, although they stated that hyperglycemia was observed in many patients with acs, they emphasized that administrating insulin requires more researches (13). a number of large therapeutic studies have attempted to explain the effect of hyperglycemia on post-acs mortality, but the lack of a general consensus on the appropriate management strategy for abnormal glycemia still remains a common issue in emergency departments. in addition, adverse outcomes risk stratification in cardiac patients and early prediction of major adverse cardiac events (mace) is a matter of importance. based on above-mentioned points, this study aims to assess the influence of admission blood glucose level (abgl) on development of 30-day mace in patients with suspected acs. 2. methods 2.1. study design and setting this is a prospective cohort study based on analysis of data collected from patients with suspected acute coronary syndrome admitted to emergency department of imamhossein hospital, tehran, iran, between june 21, 2016 and june 20, 2017. presenting blood glucose level of patients was measured and its association with development of mace within 30 days of follow-up was studied. the protocol of this study was approved by ethics committee of shahid beheshti university of medical sciences (number: ir.sbmu.retech.rec.1397.519) and researchers adhered to principals of helsinki protocol and confidentiality of patients’ information. informed consent was obtained from patients or his/her relatives before enrollment to the study. 2.2. participants patients were included if they fulfilled all of the following criteria: ≥18 years of age; ≥5 minutes of symptoms suggestive of acs; and the attending physician deciding to investigate with cardiac biomarkers. patients with a clear cause other than suspected acs for the symptoms (e.g. clinical finding of pancreatitis), transfer from another hospital, pregnancy, previous enrollment, and inability to be contacted after discharge were excluded. the american heart association (aha) case definitions for symptoms suggestive of a cardiac condition were used, which include chest pain, epigastric, jaw or arm pain, or discomfort or pressure without an apparent noncardiac source . 2.3. measurements and outcome after careful history taking, physical examination, and doing initial assessments, eligible patients were selected. nonfasting, on-admission blood glucose level was measured for all patients. blood samples for measuring blood glucose were taken from patients’ finger tips. all measurements were done by the same glucometer and the same glucose test tape. all patients were evaluated regarding the development of mace within the 30 days of follow-up. acute myocardial infarction (ami), cerebrovascular accident (cva), and all-cause mortality were considered as mace in this study. patients’ follow-up was done by a senior emergency medicine resident via phone calls. 2.4. data gathering the baseline characteristics (such as age and gender), medical history, contact information, and ecg and laboratory findings as well as 30-day outcome were recorded in special paper sheets. blood glucose level ≤90 mg/dl was considered as hypoglycemia, 91 to 126 mg/dl as normalglycemia, and >126 mg/dl as hyperglycemia. all data were collected by a senior emergency medicine resident under direct supervision of an emergency medicine specialist. 2.5. statistical analysis the statistical analyses were performed using r statistical (version 3.2.1) and spss 21 software. continuous data were presented as mean and standard deviation, and categorical data were presented as frequency and percentage. logistic regression analysis was done concerning the variables age, gender, hypertension, dyslipidemia, diabetes, family history of cardiac disease, smoking, prior ami, prior cabg, cardiac troponin and ecg changes. the relationship between the three abgl categories and mace within 30 days was analyzed. area under the roc curve (auc) was calculated in order to calculate predictive accuracy of heart score and model containing heart score and abgl. significance level was set at 0.05. 3. results 3.1. baseline characteristics of studied patients 877 patients suspected to acs were evaluated. 63 of whom were excluded (42 were missed to follow-up and 21 had incomplete data; figure 1). finally, 814 participants with the mean age of 60.8 ±13.4 (23 – 91) years were entered to analysis (58.1% male). the mean admission blood glucose level of patients was 173.7±102.2 (71 – 540) mg/dl. 64 (7.9%) patients were hypoglycemic, 324 (39.8%) normoglycemic, and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e26 figure 1: flow diagram of participant recruitment. figure 2: area under the roc curve of heart score and a model containing heart score plus blood glucose level in predicting the development of major adverse cardiac event (mace) within 30-day follow-up of acute coronary syndrome patients. 426 (52.3%) hyperglycemic at the time of admission to emergency department. mace endpoints were identified in 249 (30.6%) patients within the 30 days of follow-up (231 (28.4%) ami, 12 (1.5%) cva, and 62 (7.6%) death cases). table 1 compared the baseline characteristics of studied patients based on the presence or absence of mace. mace endpoints were developed in 166 (39.0%) hyperglycemic, 30 (46.9%) hypoglycemic, and 53 (16.4%) normoglycemic patients (p<0.001). the mean admission blood glucose level of patients who developed mace within 30 days was significantly higher than others (210.6±123.4 vs 157.4±86.6mg/dl; p<0.001; or: 1.006 (1.005 to 1.008)). the heart score of patients with mace was significantly higher (p < 0.001). 3.2. correlations there were significant correlations between male gender (p=0.027), abnormal admission blood glucose level (p<0.001), diabetes (p = 0.001), hyperlipidemia (p=0.059), prior cabg (p=0.008), first and second blood troponin levels (p<0.001), first and second abnormal ecgs (p<0.001), and also ecg changes (p<0.001) with developing mace. the results of multiple logistic regression model demonstrated that abnormal abgl, first and second blood troponin levels, and the history of diabetes were among the independent risk factors of mace within 30 days (table 1). figure 2 shows the area under the roc curve of heart score + abgl and heart score alone in predicting the development of mace (0.770 vs. 0.767). 4. discussion the present study has confirmed findings from previous reports that abnormal abgl is associated with increased risk of developing mace in acs patients. the findings showed that abgl could probably be an independent risk factor regardless of diabetic status or traditional risk factors of mace; like a similar study done by gardner et al. (14), where they demonstrated that within 30 days of follow-up, the odds of patients with abgl higher than 7 mmol/l (126 mg/dl) developing mace were 1.5 times higher than patients with an abgl<7 mmol/l. capes et al. [8] demonstrated that the relative risk of in-hospital mortality in non-diabetic mi patients with abgl>6.1 mmol/l was 3.9 times higher than patients with normal glycemia. among diabetic mi patients, those with abgl≥10 mmol/l had a 70% increase in the risk of in-hospital mortality compared to normal glycemic diabetic patients. the largest retrospective study on this subject to date, which examined the outcomes of 141680 elderly patients with mi, demonstrated a significant 13-77% increase in 30-day mortality and a 7-46% increase in 1-year mortality depending on the degree of hyperglycemia (9). in the present study, the frequency of ami endpoint was higher than cva. this probably happened due to entering acs patients to the study, most of which were affected with ami. 39.0% of hyperglycemic patients finally developed mace within 30 days. foo et al. (15) did a similar study in 3 east london hospitals over a 2-year period. they demonstrated a near-linear relationship between higher admission glucose levels and higher rates of cardiac death. particularly in glucose groups, measures being near to or far from normal glycemia affected the risk of cardiac problems. li dong-bao et al. (16) demonstrated a u-shaped relationship between admission glycemia and in-hospital mortality in ami patients, which means that hypoglycemic and hyperglycemic patients were high-risk, which matches findings of the present study. in this study, elderly people and patients with a known history of diabetes and hyperlipidemia were more at risk. in gardner et al. (14) study, the predictors of mace in addition to admission glycemia were male gender, age, hypertenthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. alavi-moghaddam et al. 4 table 1: baseline characteristics of studied patients based on development of major adverse cardiac events (mace) characteristics total mace p or (95% ci)* p yes n=249 no n=565 sex male 473 159 (33.6) 314 (66.4) 0.027 0.72(0.51-1.01) 0.065 female 341 90 (26.4) 251 (73.6) age mean ± sd 60.83± 13.40 61.5± 13.4 60.6± 13.4 0.395 1.01 (0.97-1.02) > 0.05 blood glucose level (mg/dl) on admission 173.7± 102.2 210.6± 123.4 157.4± 86.6 <0.001 1.01 (1.01-1.01) <0.001 comorbid disease hypertension 446 (54.8) 146 (32.7) 300 (67.3) 0.144 1.36 (1.01-1.82) > 0.05 hyperlipidemia 113 (13.9) 26 (23.0) 87 (77.0) 0.059 0.67 (0.43-1.04) > 0.05 diabetes 262 (32.2) 100 (38.2) 162 (61.8) 0.001 1.95 (1.43-2.64) 0.003 cardiac disease 335 (41.2) 106 (31.6) 229 (68.4) 0.586 1.23 (0.92-1.66) > 0.05 smoking 132 (16.2) 45 (34.1) 87 (65.9) 0.340 1.05 (0.71-1.56) > 0.05 history of mi 55 (6.8) 18 (32.7) 37 (67.3) 0.722 1.22 (0.69-2.15) > 0.05 prior cabg 83 (10.2) 47 (56.6) 36 (43.4) 0.008 1.95 (1.24-3.08) > 0.05 positive troponin 1s t 57 (7.0) 32 (56.1) 25 (43.9) <0.001 2.91 (1.68-5.03) 0.025 2n d 265 (32.6) 137 (51.7) 128 (48.3) <0.001 2.93 (2.16-3.99) 0.004 ecg abnormality 1s t 540 (66.3) 191 (35.4) 349 (64.6) <0.001 1.95 (1.41-2.70) > 0.05 2n d 545 (67.0) 196 (36.0) 349 (64.0) <0.001 2.16 (1.55-3.01) ecg changes positive 294 (36.1) 132 (44.9) 162 (55.1) <0.001 2.76 (2.04-3.72) > 0.05 heart score mean ± sd 6.54 ± 2.24 5.94 ± 2.32 7.88 ± 1.27 <0.001 1.75 (1.59-1.92) <0.001 ∗ unadjusted odds ratio with 95% confidence interval (ci). data are presented as mean ± standard deviation (sd) or number (%). mi: myocardial infarction; cabg: coronary artery bypass graft; ecg: electrocardiogram. sion, ischemic ecg, and positive troponin, which matches the present study; but there was a mismatch in diabetes and hypertension variables. in a study in poland, diabetes history, age, hypertension, and hypercholesterolemia had a significant relationship with mace (17). the cause of nonidentical results in various studies could be different sample sizes and the method of blood glucose assessment and study population classification. it has been debated that whether hyperglycemia has a possible direct impact on adverse outcomes or is just a secondary factor. there is a hypothesis that proposes elevated blood glucose level is a marker of illness severity (18). it has been suggested that hyperglycemia is representative of an induced stress response proportional to the ischemic myocardial damage (14). this has been found in earlier studies where the size of an infarct was associated with a corresponding degree of creatine kinase mb, cortisol and catecholamine release and an associated linear increase in glucose (19). therefore, it has been speculated that glucose may not necessarily be the causative agent leading to an increased risk of a mace; but instead may simply act as a marker indicating the extent of myocardial damage, the presence of which is necessary for a mace (20). if association of abgl with developing mace is proved, there will be hope that with more researches, measuring blood glucose level in suspected cardiac patients admitted to emergency departments can be used as a diagnostic and predictive tool for mace. 5. limitation there were some limitations in the present study. because of the large number of patients presenting to the emergency department of imam-hossein hospital, assessing all suspected acs patients was impossible and some eligible patients were probably missed. fasting status of patients was unknown and thus the results may be skewed by patients that had recently consumed a high glucose load. the main goal of treatment staff of the hospital was secure treatment of cardiac patients and therefore, the patients were not under total control of researchers. acs was diagnosed using common clinical judgments and atypical symptoms without chest discomfort were not used; this may result in missing some cases. additionally, diabetic patients presenting with silent myocardial infarction were not included. in this study, three glucose groups were considered; however, since blood glucose is a continuous variable, a cut-off with optimum diagnostic and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e26 prognostic value in acs should be found. 6. conclusion it seems that abnormal admission blood glucose level in patients with suspected acs was an independent predictor of major adverse cardiac events within 30 days. yet, additional studies with greater sample sizes in emergency departments all over the country are required before it is applied in existing or future screening tools. 7. appendix 7.1. acknowledgements the outhors would like to appreciat the staff of the clinical research development unit at imam hossein hospital, affiliated to shahid beheshti university of medical sciences, tehran, iran for their kind services to develop and release of the results of this research. 7.2. author contribution the authors met the standard criteria for authorship based on the recommendations of the international committee of medical journal editors. authors orcids mostafa alavi-moghaddam: 0000-0002-7176-023x mohammad parsa-mahjoob: 0000-0003-1269-3134 robabeh ghodssi-ghassemabad: 0000-0001-5394-5137 7.3. funding/support no fund has been received. 7.4. conflict of interest the authors report no conflicts of interest. references 1. timmer jr, ottervanger jp, de boer m-j, dambrink jhe, hoorntje jc, gosselink am, et al. hyperglycemia is an 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international journal of cardiology. 2007;116(3):315-20. 9. kosiborod m, rathore ss, inzucchi se, masoudi fa, wang y, havranek ep, et al. admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. 2005;111(23):3078-86. 10. weston c, walker l, birkhead jjh. early impact of insulin treatment on mortality for hyperglycaemic patients without known diabetes who present with an acute coronary syndrome. 2007;93(12):1542-6. 11. dandona p, chaudhuri a, ghanim h, mohanty pjricm. anti-inflammatory effects of insulin and pro-inflammatory effects of glucose: relevance to the management of acute myocardial infarction and other acute coronary syndromes. 2006;7:s25-34. 12. nice cfcpa. hyperglycaemia in acute coronary syndromes: management of hyperglycaemia in people with acute coronary syndromes. 2011. 13. ishihara mjcj. acute hyperglycemia in patients with acute myocardial infarction. 2012;76(3):563-71. 14. gardner ls, nguyen-pham s, greenslade jh, parsonage w, d’emden m, than m, et al. admission glycaemia and its association with acute coronary syndrome in emergency department patients with chest this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. alavi-moghaddam et al. 6 pain. 2015;32(8):608-12. 15. foo k, cooper j, deaner a, knight c, suliman a, ranjadayalan k, et al. a single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes. 2003;89(5):512-6. 16. dong-bao l, qi h, jincheng g, hong-wei l, hui c, shumei zjim. admission glucose level and in-hospital outcomes in diabetic and non-diabetic patients with stelevation acute myocardial infarction. 2011;50(21):24715. 17. capes se, hunt d, malmberg k, gerstein hcjtl. stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. 2000;355(9206):773-8. 18. deedwania p, kosiborod m, barrett e, ceriello a, isley w, mazzone t, et al. hyperglycemia and acute coronary syndrome: a scientific statement from the american heart association diabetes committee of the council on nutrition, physical activity, and metabolism. 2008;117(12):1610-9. 19. oswald g, smith c, betteridge d, yudkin jjbmj. determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction. 1986;293(6552):917-22. 20. norhammar a, tenerz a, nilsson g, hamsten a, efendãŋc s, ryden l, et al. glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. 2002;359(9324):2140-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e30 or i g i n a l re s e a rc h blood urea nitrogen to creatinine ratio in differentiation of upper and lower gastrointestinal bleedings; a diagnostic accuracy study seyyed mahdi zia ziabari1∗, siamak rimaz2, afshin shafaghi3, maryam shakiba4, zahra pourkazemi5, elnaz karimzadeh6, melika amoukhteh7 1. department of emergency medicine, school of medicine, guilan university of medical sciences, rasht, iran. 2. anesthesiology department, anesthesiology research center, alzahra hospital, guilan university of medical sciences, rasht, iran. 3. gi cancer screening and prevention research center, school of medicine, guilan university of medical sciences, rasht, iran. 4. school of health, guilan university of medical sciences, rasht, iran. 5. road trauma research center, school of medicine, guilan university of medical sciences, rasht, iran. 6. poursina clinical research development unit, school of medicine, guilan university of medical sciences, rasht, iran. 7. school of medicine, guilan university of medical sciences, rasht, iran. received: march 2019; accepted: april 2019; published online: 2 june 2019 abstract: introduction: finding easily accessible and non-invasive methods for differentiating various sources of gastrointestinal (gi) bleeding before performing endoscopy and colonoscopy is of great interest. the present study was designed with the aim of evaluating the screening performance characteristics of blood urea nitrogen (bun) to creatinine (cr) ratio in this regard. methods: the present diagnostic accuracy study was performed on patients with acute gi bleeding presenting to emergency department from 2011 to 2016, in a retrospective manner. bun/cr ratio was calculated for all patients and its accuracy in differentiation of upper and lower gi bleedings, confirmed via endoscopy or colonoscopy, was evaluated. results: a total of 621 patients with the mean age of 59.49±17.94 (5 – 93) years were studied (60.5% male). area under the receiver operating characteristic (roc) curve of bun/cr ratio for predicting the source of gi bleeding was 0.63 (95% ci: 0.57 – 0.68). sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of bun/cr ratio at 35 cut-off point were 19.63% (95%ci: 16.69 – 23.45), 90.16% (95%ci: 83.11 – 94.88), 89.09 (95%ci: 81.35 – 93.98), 21.53 (95%ci: 18.09 – 25.39), 8.16 (95%ci:4.76 – 13.98), and 3.65 (95%ci: 3.44 – 3.87), respectively. conclusion: considering the relatively proper specificity and positive predictive value of bun/cr ratio, in cases that bleeding source cannot be determined using other non-invasive methods, values higher than 35 can predict upper gi bleeding with high probability. however, due to the low sensitivity, values less than 35 are not diagnostic. keywords: gastrointestinal hemorrhage; blood urea nitrogen; creatinine; clinical decision-making; decision support techniques cite this article as: zia ziabari s m, rimaz s, shafaghi a, shakiba m, pourkazemi z, karimzadeh e, amoukhteh m. blood urea nitrogen to creatinine ratio in differentiation of upper and lower gastrointestinal bleedings; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e30. ∗corresponding author: seyyed mahdi zia ziabari; emergency department, poursina hospital, rasht, iran. tel: 00989111375056, email: smzz102186@gmail.com 1. introduction gastrointestinal (gi) bleedings are among common causes of emergency department visits and there are about 800000 visits with complaint of gi bleeding every year only in the united states, about half of which will need hospitalization (1). gi bleedings are divided into two groups of upper (above treitz ligament) and lower (below treitz ligament) based on this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s m. zia ziabari et al. 2 the site of bleeding. annual incidence of upper gi bleeding is higher than lower gi bleeding and mortality due to upper gi bleeding has been estimated to be up to 40% for those with unstable hemodynamics (2, 3). meanwhile, this rate has been between 10% and 20% for lower gi bleeding (4). differentiation of upper and lower gi bleeding is very important for choosing the proper treatment modality. for this purpose, various tools such as history taking, clinical examination, and laboratory parameters (like hemoglobin, platelet, c reactive protein) as well as invasive diagnostic treatment methods such as endoscopy and colonoscopy are available (5-7). finding easily accessible and non-invasive methods for differentiating various types of upper gi bleeding before performing endoscopy and colonoscopy is of great interest. among the laboratory parameters that can be used for differentiation of upper and lower gi bleeding, blood urea nitrogen (bun) can be pointed out (8). decrease in blood flow to the kidney, secondary to losing volume due to bleeding and also digestion of blood in the digestive system and metabolization of proteins resulting from it to bun in the urea cycle are introduced as the reasons for increase in the level of this biomarker (3, 8). if the cause of azotemia is degradation of blood in the digestive system, it is expected that higher bun levels more strongly correlate with upper gi bleeding. some studies have used bun to creatinine (cr) ratio as an index to differentiate upper and lower gi bleedings and have shown that higher bun to cr ratio is associated with higher probability of upper gi bleeding (8, 9). on the other hand, other studies have shown that bun and bun/cr ratio levels lack the required accuracy in differentiation of upper and lower gi bleeding (10, 11). therefore, considering the existing disagreements, the present study was designed and performed with the aim of evaluating the screening performance characteristics of bun to cr ratio in differentiation of upper and lower gi bleedings. 2. methods 2.1. study design and setting the present diagnostic accuracy study was performed on patients with acute gi bleeding presenting to the emergency department of razi hospital, rasht, iran, from 2011 to 2016 and screening performance characteristics of bun to creatinine ratio regarding source of bleeding (upper or lower digestive system) were evaluated. protocol of the study was approved by the ethics committee of guilan university of medical sciences under the number ir.gums.rec.1396.432 and researchers adhered to confidentiality of patients’ data. this study was carried out in a retrospective manner using patients’ medical profiles. 2.2. participants all the patients that had presented to the emergency department with acute gi bleeding manifesting as hematemesis, melena, and hematochezia and less than 24 hours had passed from their bleeding were included in the study. these patients should have had bun and cr evaluations on admission and finally, their source of gi bleeding should have been determined using a reliable method such as endoscopy or colonoscopy with evidence present in the profile. patients with a history of confirmed renal failure (where cr levels were above 120 µmol/l or 2.16 mg/dl in the last 3 months or they had undergone dialysis), those who had received blood transfusion during the 24 hours prior to admission, and those showing evidence of thrombocytopenia or coagulopathy or having a history of injecting cephalosporins or any other drug interfering with bun or cr evaluation, as well as patients with both upper and lower gi bleeding were excluded from the study. 2.3. data gathering census sampling was used for data gathering. a checklist consisting of demographic data (age and sex), underlying illnesses (diabetes, hypertension, cardiovascular disease, liver cirrhosis), history of gi bleeding, history of upper or lower gi cancer, history of cigarette, alcohol, or tobacco addiction, history of medication use (aspirin, non-steroidal anti-inflammatory drugs (nsaid), steroid, warfarin, iron or bismuth), and laboratory findings (cr, bun, platelet (plt), hemoglobin (hb)) as well as the accurate source of bleeding according to endoscopy or colonoscopy findings was filled for all the patients presenting to the emergency department with gi bleeding during the mentioned time by referring to their medical profile. patients whose source of bleeding was determined to be over the treitz ligament using endoscopy were reported as upper gi bleeding, and if the source of bleeding was not detected in endoscopy and the site of bleeding was not seen in colonoscopy, the case was considered as a lower gi bleeding with negative colonoscopy and if the source of bleeding was not detected in endoscopy or endoscopy was not performed and bleeding was observed in colonoscopy, the case was considered as lower gi bleeding with positive colonoscopy. two medical interns were responsible for gathering data under supervision of an emergency medicine specialist. 2.4. statistical analysis minimum required sample size was determined to be 630 patients based on 69% sensitivity for bun/cr ratio (9) and estimating and considering 20% prevalence for upper gi bleeding and type 1 error of 0.05 and 8% desired precision. all the data were analyzed in stata version 13.0 (statacorp, college this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e30 table 1: comparing baseline characteristics of patients with upper and lower gastrointestinal (gi) bleedings variable source of gi bleeding p value upper lower sex male 298 (59.7) 78 (63.9) 0.72 female 201 (40.3) 44 (36.1) age (year) mean ± standard deviation 60.27 ± 17.91 56.29 ± 17.76 0.028 underlying illness diabetes 110 (22.0) 24 (19.7) 0.32 hypertension 195 (39.1) 45 (36.9) 0.19 cardiovascular diseases 91 (18.2) 19 (15.6) 0.47 cirrhosis 17 (3.4) 0 (0.0) 0.039 history of gi bleeding 97 (19.4) 28 (23) 0.38 history of gi cancer 8 (1.6) 5 (4.1) 0.08 history of addiction alcohol 22 (4.4) 4 (3.3) 0.5 cigarette 104 (20.8) 23 (18.9) 0.6 drugs 76 (15.2) 22 (18) 0.44 history of medication nsaid 94 (18.8) 23 (18.9) 0.99 corticosteroid 6 (1.2) 1 (0.8) 0.72 warfarin 22 (4.4) 8 (6.6) 0.32 iron 62 (12.4) 19 (15.6) 0.35 bismuth 6 (1.2) 2 (1.6) 0.70 data are presented as frequency (%). nsaid: non-steroidal anti-inflammatory drugs. table 2: comparing the laboratory findings of patients with upper and lower gastrointestinal (gi) bleedings variable source of gi bleeding p value upper lower hemoglobin (mg/dl) 9.36 ± 2.45 9.90 ± 2.42 0.014 bun (mg/dl) 28.81 ± 18.62 20.62 ± 14.14 0.001 creatinine (mg/dl) 1.25 ± 1.15 1.00 ± 0.33 0.032 platelet (/mcl) 219700 ± 8990 238065 ± 8192 0.007 bun/creatinine ratio 25.90 ± 15.16 21.16 ± 13.77 0.001 data are shown as mean ± standard deviation. bun: blood urea nitrogen. station, tx, usa) statistical software after gathering. to compare the groups regarding qualitative indices, chi square, and for comparing quantitative indices, t-test were used. sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were calculated and reported for the best cut-off point of bun/cr ratio in differentiation of upper and lower gi bleedings. the best cut-off point was calculated using the area under the receiver operating characteristic (roc) curve. p values ≤ 0.05 were considered significant. 3. results a total of 621 patients with the mean age of 59.49±17.94 (5 – 93) years were studied (60.5% male). based on the results of endoscopy and colonoscopy, 499 (80.35%) bleeding cases were related to the upper digestive system and 122 (19.65%) cases were related to the lower digestive system. tables 1 and 2 have compared the baseline and laboratory characteristics of patients with upper and lower gi bleeding. the two groups were similar regarding sex distribution (p = 0.72), history of underlying illnesses (p > 0.05), history of drug abuse (p > 0.05), and history of taking medications (p > 0.05). mean age of the patients with lower gi bleeding was about four years lower (p = 0.028), bun/cr ratio was significantly higher in those with upper gi bleeding (25.90 ± 15.16 versus 21.16 ± 13.77; p = 0.001). area under the roc curve of bun/cr ratio for predicting the source of gi bleeding was 0.63 (95% ci: 0.57 – 0.68) (figure 1). the best cut-off point of bun/cr ratio for predicting the source of bleeding was estimated as 35.13. sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of bun/cr ratio at this cut-off point were 19.63% (95%ci: 16.69 – 23.45), 90.16% (95%ci: 83.11 – 94.88), 89.09 (95%ci: 81.35 – 93.98), this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s m. zia ziabari et al. 4 figure 1: area under the receiver operating characteristic (roc) curve of blood urea nitrogen (bun)/creatinine ratio for predicting the source of gastrointestinal bleeding (upper or lower). 21.53 (95%ci: 18.09 – 25.39), 8.16 (95%ci:4.76 – 13.98), and 3.65 (95%ci: 3.44 – 3.87), respectively. 4. discussion based on the results of the present study, considering the acceptable specificity and positive predictive value of bun/cr ratio, in cases that the source of bleeding cannot be determined via other non-invasive methods, values higher than 35 predict an upper source for the gi bleeding with high probability. in this study, the rate of bun is higher in patients with upper gi bleeding compared to those with lower gi bleeding. the level of bun in blood increases following digestion of a high volume of blood or protein in the digestive system. the source of voluminous gi bleeding is mostly above the treitz ligament and therefore, blood has more time for absorption and catabolism in the digestive system. therefore, it is expected that upped gi bleedings have higher bun compared to lower gi bleedings. on the other hand, the cause of lower gi bleedings is usually in the colon and considering the low absorption of nutrients in colon, it is expected that patients with lower gi bleedings have lower bun levels. meanwhile, upper gi bleeding cases probably have higher creatinine levels due to losing more volume. in the present study, mean bun/cr ratio was 25.90 ± 15.16 in patients with upper gi bleeding and 21.16 ± 13.77 in those with lower gi bleeding (p value = 0.001). in a study in 2015, which was performed on 141 patients with upper and lower gi bleeding, tomizawa et al. showed that bun measure alone can differentiate upper and lower gi bleedings. in their study, they considered bun>21 as the threshold and expressed that bun over 21 indicates upper gi bleeding with 36.4% sensitivity and 93% specificity (7). in a study conducted on 124 patients with gi bleeding, ernest et al. showed that bun/cr ratio significantly correlated with upper gi bleeding (8). additionally, in the study by urashima et al. on 85 children with gi bleeding, bun/cr ratio was significantly different between the upper and lower gi bleeding groups. bun/cr ratio of 30 or higher had 98% specificity and 68.8% sensitivity in detection of upper gi bleeding (9). richards et al. also conducted a retrospective study on 74 patients with upper gi bleeding and 52 patients with lower gi bleeding and showed that none of the patients with lower gi bleeding had a bun/cr ratio equal to or higher than 36, while 38% of the patients with upper gi bleeding had a bun/cr ratio equal to or higher than 36 (10). as can be seen, various studies have been in line with our study regarding significance of bun/cr ratio in differentiation of the source of bleeding. it seems that in cases with acute gi bleeding and when patients are hemodynamically stable, if the diagnosis of bleeding source is ambiguous based on the clinical examination of the patient, and aspiration of nasogastric discharge of the patient does not help, bun/cr ratio can be applied as an index for differentiating the site of bleeding in the digestive system. for this purpose, using a simple and inexpensive blood test, if this ratio was calculated to be over 35 (considering the positive predictive value and high specificity) the source of bleeding can be considered upper digestive system with high probability and if the ratio was lower than 35 (considering the low sensitivity and negative predictive value) this index does not help in differentiating the source of bleeding and other diagnostic measures are needed. 5. limitation hypovolemia is a major factor in elevating plasma urea levels, and it would have been better if patients were matched regarding hypovolemia rate using hematocrit and urine output rate. 6. conclusion considering the relatively proper specificity and positive predictive value of bun/cr ratio, in cases that bleeding source cannot be determined using other non-invasive methods, values higher than 35 can predict upper gi bleeding with high probability. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e30 7. appendix 7.1. acknowledgements all the staff members of razi hospital, rasht, iran are thanked for their cooperation throughout the course of the project. 7.2. author contribution all the authors met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. authors orcids seyyed mahdi zia ziabari: 0000-0002-3708-7723 siamak rimaz: 0000-0002-5268-5297 afshin shafaghi: 0000-0001-6782-5902 maryam shakiba: 0000-0002-7497-6001 zahra pourkazemi: 0000-0002-7368-455x elnaz karimzadeh: 0000-0003-0749-2741 melika amoukhteh: 0000-0003-3488-8960 7.3. funding/support no fund has been received for performing this project. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. peery af, crockett sd, barritt as, dellon es, eluri s, gangarosa lm, et al. burden of gastrointestinal, liver, and pancreatic diseases in the united states. gastroenterology. 2015;149(7):1731-41. e3. 2. kumar r, mills am. gastrointestinal bleeding. emergency medicine clinics of north america. 2011;29(2):23952. 3. tomizawa m, shinozaki f, hasegawa r, shirai y, motoyoshi y, sugiyama t, et al. patient characteristics with high or low blood urea nitrogen in upper gastrointestinal bleeding. world journal of gastroenterology: wjg. 2015;21(24):7500-5. 4. feinman m, haut er. lower gastrointestinal bleeding. surg clin north am. 2014;94(1):55-63. 5. tomizawa m, shinozaki f, hasegawa r, togawa a, shirai y, ichiki n, et al. reduced hemoglobin and increased creactive protein are associated with upper gastrointestinal bleeding. world journal of gastroenterology: wjg. 2014;20(5):1311-7. 6. sittichanbuncha y, senasu s, thongkrau t, keeratikasikorn c, sawanyawisuth k. how to differentiate sites of gastrointestinal bleeding in patients with hematochezia by using clinical factors? gastroenterology research and practice. 2013;2013:265076. 7. tomizawa m, shinozaki f, hasegawa r, shirai y, motoyoshi y, sugiyama t, et al. laboratory test variables useful for distinguishing upper from lower gastrointestinal bleeding. world journal of gastroenterology: wjg. 2015;21(20):6246-51. 8. ernst aa, haynes ml, nick tg, weiss sj. usefulness of the blood urea nitrogen/creatinine ratio in gastrointestinal bleeding. the american journal of emergency medicine. 1999;17(1):70-2. 9. urashima m, toyoda s, nakano t, matsuda s, kobayashi n, kitajima h, et al. bun/cr ratio as an index of gastrointestinal bleeding mass in children. journal of pediatric gastroenterology and nutrition. 1992;15(1):89-92. 10. richards rj, donica mb, grayer d. can the blood urea nitrogen/creatinine ratio distinguish upper from lower gastrointestinal bleeding? journal of clinical gastroenterology. 1990;12(5):500-4. 11. kim ks, kang ch, kim jy. availability of blood urea nitrogen/creatinine ratio in gastrointestinal bleeding with melena in children. pediatric gastroenterology, hepatology & nutrition. 2015;18(1):30-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e64 or i g i n a l re s e a rc h association of clinical signs and symptoms with abnormal urinalysis findings of blunt trauma patients; a crosssectional study bahram zarmehri1, ayeh shouman1, elham pishbin1, niaz-mohammad jafari chokan1, mona najaf najafi2, seyed reza habibzadeh1, esmaeil rayat dost3, mahdi foroughian1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. clinical research unit, mashhad university of medical sciences, mashhad, iran. 3. department of emergency medicine, jahrom university of medical sciences, jahrom, iran. received: august 2019; accepted: october 2019; published online: 11 november 2019 abstract: introduction: urinalysis (ua) is performed routinely as a diagnostic screening test for trauma patients in most centers. this study aimed to examine the relationship between patients’ clinical signs and symptoms with ua findings. methods: this cross-sectional study was carried out on multiple trauma patients between 18 to 65 years old, who were referred to the emergency department. ua was performed for all patients and its association with clinical signs and symptoms (pain, tenderness, abrasion, ecchymosis, hematoma, etc.) in abdomen, back, flank, and inferior hemi-thorax was evaluated. results: 640 patients with the mean age of 39.8 ± 11.2 years were studied (65.0% males). 271 (42.4%) cases had associated injuries and 554 (86.6%) cases had at least one sign or symptom of trauma in abdomen, back, flank or inferior hemi-thorax. 146 (22.8%) patients had negative ua. among cases with positive ua, 364 (56.9%) cases had microscopic hematuria with rbc < 25/hpf, 60 (9.4%) had microscopic hematuria with rbc ≥ 25/hpf and 70 (10.9%) had gross hematuria. none of the asymptomatic patients had microscopic hematuria with rbc ≥ 25/hpf and gross hematuria (p <0.001). symptomatic patients who had signs in the abdomen, back or inferior hemi-thorax mainly had microscopic hematuria with rbc < 25/hpf, but those with signs in the flank, mainly had microscopic hematuria with rbc ≥ 25/hpf (p<0.001). patients with pain, tenderness, abrasion, and ecchymosis in flank had a higher risk of positive ua findings (figure 2; p <0.001). conclusion: based on the findings of the present study, patients with any findings of pain, tenderness, abrasion, or ecchymosis in flank had higher risk of abnormal ua and perhaps urogenital injuries. none of the asymptomatic patients had microscopic hematuria with rbc ≥ 25/hpf and gross hematuria. keywords: urinalysis; urogenital system; hematuria; multiple trauma; signs and symptoms cite this article as: zarmehri b, shouman a, pishbin e, jafari chokan n, najaf najafi m, habibzadeh s r, rayat dost e, foroughian m. association of clinical signs and symptoms with abnormal urinalysis findings of blunt trauma patients; a cross-sectional study. arch acad emerg med. 2019; 7(1): e64. 1. introduction trauma is the main cause of mortality in people aged 1-44 years (1). it accounts for more than 6 million deaths, yearly (2). trauma related injuries are the main cause of longlasting morbidity and disability, especially in young patients with their productive years ahead (3, 4). although in the last ∗corresponding author: mahdi foroughian; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: 05138525312, email: foroughianmh@mums.ac.ir five decades management of trauma patients has advanced, trauma remains a serious health problem in all societies with different economic, social and health conditions (5). according to previous studies, abdomen is the third most common site in the body that requires surgical intervention following trauma. nevertheless, the evaluation and diagnosis of intra-abdominal injury is still a challenge for doctors dealing with these patients (6). most damage to abdominal organs is caused by abdominal blunt trauma (7, 8). abdominal trauma could include genitourinary trauma, which includes a wide range of organs such as kidneys, ureters, bladder, urethra, penis, scrotum, and testicles (1). kidneys are the most this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. zarmehri et al. 2 commonly affected organs in urinary trauma. they are injured in 5% of all traumas and in 10% of abdominal traumas (9). renal and genitourinary trauma is seen in all age groups and in both sexes, although it is more common in men compared to women (10). early identification and appropriate management of genitourinary tract damage can reduce potential long-term complications, including renal failure, chronic hypertension, urinary incontinence and sexual dysfunction (11). signs, symptoms and findings of clinical examinations in patients with genitourinary trauma are diverse and non-specific. these manifestations may include abdominal, rib, back, pelvic or testicular pain, urinary retention, penile and scrotal hematoma or ecchymosis and blood in the urethral meatus. in trauma patients, abdominal and pelvic computed tomography (ct) scan, with intravenous contrast, is the gold standard for detecting kidney injury. however, to prevent the complications of this diagnostic method, urinalysis (ua) is performed as a screening test to determine the cases requiring ct scan (10). the negative results of urine tests in most of the cases, suggest that routine performance of this test must be reconsidered. therefore, this study aimed to evaluate the relationship between clinical symptoms and ua findings of multiple trauma patients. 2. methods 2.1. study design and setting this cross-sectional study was carried out on multiple trauma patients, who were referred to the emergency department of hashemi nejad hospital, mashhad, iran, between september 2017 and september 2018. ua was performed for all patients and the association of ua with clinical signs and symptoms was evaluated. in the beginning of the project, the aim of the study was explained to the patients and after completing the informed consent form, patients were included. this research was approved by the committee on organizational ethics of the faculty of medical sciences, mashhad university of medical sciences (ir.mums.fm.rec.1396.64). 2.2. participants patients less than 18 years of age, those with previous renal disease (such as stones, cysts, tumors, chronic kidney disease, single kidneys), unstable hemodynamic, urinary tract infection, clear symptoms of duct injury (such as hematoma in perineum and blood at the meatus of the penis), and unreliable examination (e.g. loss of consciousness, poisoning), those who were pregnant or on their menstrual period, and patients with penetrating trauma were excluded. 2.3. data gathering on admission to the emergency department a complete history was obtained and registered for each patient including demographic features such as gender and age, location of trauma (abdomen, flank, back, inferior hemi-thorax, and other locations), trauma mechanism (e.g. falling, vehicle crash, motorcycle, pedestrian crash, direct abdominal trauma, direct back trauma, direct inferior hemi-thorax trauma, sudden impact injury), signs and symptoms (including pain, tenderness, abrasion, ecchymosis and hematoma in the abdomen, back, flank and inferior hemi-thorax), and associated injuries (inferior rib fracture, thoracolumbar vertebral fracture, pelvic fracture, long bone fracture, intraabdominal bleeding). information about each patient was recorded using appropriate codes. ua was requested within 24 hours after trauma. urine test results were divided into 4 separate categories including negative ua, gross hematuria, microscopic hematuria with rbc (red blood cells) <25/hpf and microscopic hematuria with rbc ≥ 25/hpf. all of these data were collected and put in a checklist. the urine test was interpreted by a blinded laboratory technician. a trained emergency medicine resident was responsible for data gathering. 2.4. statistical analysis data were analyzed via spss version 16 software. demographic data were presented using descriptive statistical methods, including central indicators, distribution and frequency distribution, in the form of appropriate tables and charts. anova test was used to compare quantitative variables between the four groups (based on the results of ua). chi-square test was used to compare qualitative variables between the four groups. in all calculations, p-value of 0.05 was considered as the level of significance. 3. results 3.1. baseline characteristics of studied patients a total of 640 patients with the mean age of 39.8 ± 11.2 years were studied (65.0% males). table 1 summarizes the baseline characteristics of studied patients. the most frequent mechanisms of trauma were pedestrian-vehicle accident (39.8%), motorcycle accident (34.4%), and falling (19.2%). 271 (42.4%) cases had associated injuries and 554 (86.6%) cases had at least one sign or symptom of trauma in abdomen, back, flank or inferior hemi-thorax. distribution of clinical findings in mentioned locations are presented in table 2. 3.2. ua and clinical symptoms 146 (22.8%) patients had negative ua. among cases with positive ua, 364 (56.9%) cases had microscopic hematuria this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e64 table 1: baseline characteristics of studied patients variables number (%) gender male 416 (65.0) female 224 (35.0) trauma mechanism falling down 123 (19.2) motorcycle accident 220 (34.4) pedestrian-vehicle accident 255 (39.8) direct abdominal trauma 17 (2.7) direct trauma (flank, back,. . . ) 25 (3.9) associated injuries1 inferior rib fracture 9 (3.3) thoracolumbar vertebral fractures 41 (15.1) pelvic fractures 36 (13.2) long bone fractures 199 (73.4) intra-abdominal hemorrhage 19 (1.1) clinical signs and symptoms2 pain 502 (90.6) tenderness 399 (72.2) abrasion 169 (30.5) ecchymosis 96 (17.1) hematoma 26 (4.6) 1: some patients had more than one associated damage. 2: findings of abdomen, back, flank, and inferior hemithorax examination. with rbc < 25/hpf, 60 (9.4%) had microscopic hematuria with rbc ≥ 25/hpf and 70 (10.9%) had gross hematuria. there was not any significant relationship between age (p = 0.83), gender (p = 0.83), mechanisms of trauma (p = 0.29), or presence of associated injuries (p = 0.456) and ua findings. figure 1 and table 3 show the distribution of ua findings based on presence or absence of symptoms. none of the asymptomatic patients had microscopic hematuria with rbc ≥ 25/hpf and gross hematuria (p <0.001). symptomatic patients who had signs in the abdomen, back or inferior hemithorax mainly had microscopic hematuria with rbc < 25, but those with signs in the flank, mainly had microscopic hematuria with rbc ≥ 25/hpf (p<0.001). patients with pain, tenderness, abrasion, and ecchymosis in flank had a higher risk of abnormal ua (figure 2; p <0.001). 4. discussion based on the findings of the present study, patients with any findings of pain, tenderness, abrasion, or ecchymosis in flank had a higher risk of abnormal ua and perhaps urogenital injuries. none of the asymptomatic patients had microscopic hematuria with rbc ≥ 25/hpf and gross hematuria. in most centers, including ours, ua is used as a screening test to diagnose intra-abdominal injuries, including renal injury. however, the high number of normal results of this para-clinical method suggests that we need to create reliable clinical decision rules that could identify low-risk patients who do not require para-clinical examination. the most common mechanism of trauma in the present study was pedestrian accident (39.8%). 50% of patients with direct flank trauma had microscopic hematuria with rbc ≥ 25/hpf. this indicates the importance of this mechanism in predicting renal injury and the need for ua in this case, although there was no statistically significant correlation between injury mechanism and ua results. results of ua showed that most symptomatic patients have microscopic hematuria with rbc <25/hpf, or have negative ua results. in addition, none of the asymptomatic patients had gross hematuria or microscopic hematuria with rbc≥25/hpf. this suggests that if the patient does not have clinical symptoms, ua may be discarded. moreover, 36.2% of patients with clinical symptoms in the flank area had microscopic hematuria with rbc ≥ 25/hpf. 37.3% of the patients with flank pain, 48.4% of patients with flank tenderness, 44% of patients with flank abrasion, 54.5% of patients with flank ecchymosis, and 30% of patients with flank hematoma, had microscopic hematuria with rbc ≥ 25/hpf. the rate of microscopic hematuria with rbc ≥ 25/hpf was lower in other areas. this indicates the importance of these symptoms in the flank area. it should be noted that presence of ecchymosis and hematoma did not significantly correlate with ua results, which is probably due to the small number of patients with these symptoms in the study. in categorizing patients into two groups of high risk for renal injury (microscopic hematuria with rbc ≥ 25/hpf or gross hematuria) and low risk for renal injury (negative ua or microscopic hematuria with rbc <25/hpf), the frequency of flank symptoms including tenderness, abrasion, and ecchymosis was significantly higher in those with a high risk of renal injury. this also signifies the importance of symptoms in the flank area. it can be concluded that the symptoms in the flank area are very important, and if there are symptoms in this area para-clinical examination, including ua, is necessary to detect or rule out renal injury. holmes et al. (2009) reviewed the rules that predict the risk of intra-abdominal injury to be low in patients with blunt abdominal trauma. the results showed that the use of a combination of glasgow coma scale (gcs) less than 14, rib tenderness, abdominal tenderness, femoral fractures, hematuria with rbc more than 25/hpf, hematocrit less than 30%, and abnormal chest radiography had 8.95% sensitivity, 29.9% specificity and 6.98% negative predictive value in the determination of intra-abdominal injury. while, some of the criteria reviewed in this study differ from the criteria of our study, the results of the two studies are similar. patients without the symptoms mentioned in the study had a lower risk of intraabdominal injury (especially injuries requiring surgical intervention) and it seemed that patients would not benefit from this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. zarmehri et al. 4 table 2: distribution of clinical signs and symptoms according to their location location pain tenderness abrasion ecchymosis hematoma abdomen 205 (40.8) 174 (43.6) 78 (46.2) 53 (55.2) 13 (50) back 199 (39.6) 150 (37.6) 59 (34.9) 25 (26) 2 (7.7) flank 83 (16.5) 62 (15.5) 25 (14.8) 11 (11.5) 10 (38.5) hemi-thorax 15 (3) 13 (3.3) 7 (4.1) 7 (7.3) 1 (3.8) * some patients had more than one clinical symptom. data are presented as frequency (%). table 3: distribution of patients in terms of clinical symptoms, site of injury and urinalysis location urinalysis p negative rbc < 25 rbc ≥ 25 gross hematuria symptomatic patients abdomen 52(24.6) 125(59.2) 10 (4.7) 24(11.4) back 33(14.2) 150(64.4) 16(6.8) 34(14.6) 0.001 flank 20(21.3) 30(31.9) 34(36.2) 10(10.6) hemi-thorax 3(18.8) 11(68.8) 0 2(12.4) pain abdomen 49(23.9) 124(60.5) 10(4.9) 22(10.7) back 28(14.1) 128(64.3) 15(7.5) 28(14.1) 0.001 flank 19(2.9) 3(27.8) 31(37.3) 10(12) hemi-thorax 3(20) 10(66.7) 0 2(3.3) tenderness abdomen 44(25.3) 100(57.5) 10(5.7) 20(11.5) back 20(13.3) 99(66) 13(8.7) 18(12) 0.001 flank 8(12.9) 18(29) 30(48.4) 6(9.7) hemi-thorax 1(7.7) 10(76.9) 0 2(15.4) abrasion abdomen 23(29.5) 37(47.4) 6(7.7) 12(15.4) back 12(20.03) 28(47.5) 12(20.03) 7(11.09) na flank 5(20) 5(20) 11(44) 4(16) hemi-thorax 2(28.6) 4(57.1) 0 1(14.3) ecchymosis abdomen 12(22.6) 30(56.6) 6(11.3) 5(9.4) back 5(20) 12(48) 6(20) 3(12) na flank 2(18.2) 2(18.2) 6(54.5) 1(9.1) hemi-thorax 2(28.6) 4(57.1) 0 1(14.3) hematoma abdomen 4(30.8) 6(46.2) 2(15.4) 1(17.6) back 0 2(100) 0 0 na flank 2(20) 2(20) 3(30) 3(30) hemi-thorax 0 1(100) 0 0 data are presented based on frequency (%). rbc: red blood cell count per high power field. ct scan. note that, in this study, intra-abdominal injury was studied in general, while in our study only the predictors of renal injury were considered (12). jones et al. also reviewed the value of ua in blunt trauma patients in 2017. ua was normal in 810 patients (45%). among these 810 patients, 2 (0.2%) had genitourinary injury, but none of them required intervention. the researchers concluded that negative ua plays an important role in predicting or ruling out urogenital and intra-abdominal injuries. this helps in preventing exposure to unnecessary radiation. in this study, clinical manifestations had not been studied and the relationship of ua results with urogenital injury was examined, but in general, it is consistent with the results of our study (13). in 2016 sabzghabaei et al examined 325 patients with abdominal blunt trauma. in this study, urine test results were normal in about half of patients. the results of ct scan of 193 patients (59.6%) were normal overall and 90% were normal for kidney injury, where 32 (10%) had kidney injury. the researchers stated that ua has a low diagnostic value in predicting intra-abdominal injury in trauma patients, and it could be used as a helpful diagnostic tool, along with other sources, such as clinical findings and imaging. unlike our study, this study did not address the clinical symptoms, but its conclusion was confirmed by our findings as it recomthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e64 figure 1: distribution of urinalysis findings based on presence or absence of symptoms (pain, tenderness, abrasion, hematoma, etc.) in abdomen, back, flank or inferior hemi-thorax. rbc: red blood cell count per high power field. figure 2: association of clinical signs and symptoms with the risk of abnormal urinalysis findings (p < 0.001). mended the use of clinical findings as a diagnostic tool (14). in the same context, mustafa et al. (2017) studied the value of ua in patients with abdominal blunt trauma. out of the 100 patients who participated in the study, 56 had microscopic hematuria, 17 of which had gross hematuria, and 44 had no hematuria. most patients who had intra-abdominal injury had hypovolemic shock (or: 8.4, ci95%: 2.7-26), abdominal wall hematoma (or: 3.1, ci95%: 1.2-7.9), and/or anemia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. zarmehri et al. 6 (or: 3.6; ci95%: 1.2-10.3), at the time, ua was not successful in predicting intra-abdominal injury. the researchers concluded that the use of ua is not effective enough to predict intra-abdominal injury, and should therefore not be used as a key component in patients with blunt abdominal trauma. although the clinical criteria of this study differ from our study, the results of both studies are similar and indicate the importance of clinical symptoms in comparison to ua (15). in 2015, olthof et al. conducted a retrospective study, to examine the validity of ua in predicting traumatic urogenital injury. the incidence of intra-abdominal injury and urogenital injury were 13% and 8%, respectively. in this study, regardless of imaging findings, gross hematuria was detected in 73% of cases with urogenital injury, whereas microscopic hematuria was detected in only 4% of those patients. olthof’s study, like our study, proves that ua is not an appropriate tool for predicting intra-abdominal injury. therefore, the researchers suggested that ua should be removed from routine trials in patients with blunt trauma and should only be used in specific cases. note that, in contrast to our study, which was intended only for renal injury, this study examined general intra-abdominal injuries (16). not only studies on ua have shown the importance of clinical symptoms to decide on further para-clinical examinations and the need of screening tools, other studies investigating intra-thoracic damage have also shown the importance of clinical symptoms in determining the need for further para-clinical studies, which confirms our results. in most centers, including our center, routine ua is requested for all multiple trauma patients. this study demonstrates the importance of clinical symptoms for determining the need for para-clinical interventions and suggests the use of clinical signs to predict renal injury, which in turn prevents the imposition of additional costs and emergency crowding. 5. limitation one of the limitations of this study was the lack of ct scans of participating patients due to its high costs and complications. in addition, this study only covers patients who were referred to the emergency department of hashemi nejad hospital. since genitourinary trauma is associated with intra-abdominal trauma in many cases, and since hematuria is one of the symptoms of intra-abdominal injury, it would have been better to exclude patients with intra-abdominal injury. on the other hand, the focus on kidney injury and clinical symptoms is one of the strengths of this study. in order to increase the validity of the results, we suggest that for future studies, in addition to the registration of symptoms and clinical signs and hematuria, the study must be multicentered and include ct scans of patients. 6. conclusion based on the findings of the present study, patients with any findings of pain, tenderness, abrasion, or ecchymosis in flank had a higher risk of abnormal ua and perhaps urogenital injuries. none of the asymptomatic patients had microscopic hematuria with rbc ≥ 25/hpf and gross hematuria. 7. appendix 7.1. acknowledgements this study was the result of a doctoral research thesis conducted by dr. ayeh shouman, which was sponsored by research deputy of mashhad university of medical sciences under grant code 951246. we would also like to thank the clinical research and development unit of peymanieh educational, research and therapeutic center of jahrom university of medical sciences for revising the manuscript. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids bahram zarmehri: 0000-0002-8687-1821 elham pishbin: 0000-0002-3082-8074 niaz-mohammad jafari chokan: 0000-0003-1872-574x mona najaf najafi: 0000-0003-4962-6787 seyed reza habibzadeh: 0000-0003-4569-1776 esmaeil rayat dost: 0000-0002-9430-7913 mahdi foroughian: 0000-0002-3944-9361 7.3. funding/support this study was sponsored by research deputy of mashhad university of medical sciences under grant code 951246. 7.4. conflict of interest there are no conflicts of interest regarding this study. references 1. walls r, hockberger r, gausche-hill m. rosen’s emergency medicine-concepts and clinical practice e-book: elsevier health sciences; 2017. 2. curry n, davis p. what’s new in resuscitation strategies for the patient with multiple trauma? injury. 2012;43(7):1021-8. 3. organization wh. violence, injuries and disability: biennial report 2008-2009. 2010. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e64 4. murray cj, lopez ad. global mortality, disability, and the contribution of risk factors: global burden of disease study. the lancet. 1997;349(9063):1436-42. 5. rice dp. cost of injury in the united states: a report to congress, 1989: institute for health & aging, university of california, san francisco; 1989. 6. tan w, chen c, chiang h. the value and role of computed tomography in blunt injury of the abdomen. zhonghua yi xue za zhi= chinese medical journal; free china ed. 1991;48(2):116-20. 7. mcaninch jw. genitourinary trauma. urologic clinics. 2006;33(1):xiii. 8. poletti pa, mirvis se, shanmuganathan k, takada t, killeen kl, perlmutter d, et al. blunt abdominal trauma patients: can organ injury be excluded without performing computed tomography? journal of trauma and acute care surgery. 2004;57(5):1072-81. 9. bregstein js, lubell tr, ruscica am, roskind cg. nuking the radiation: minimizing radiation exposure in the evaluation of pediatric blunt trauma. current opinion in pediatrics. 2014;26(3):272-8. 10. santucci r, wessells h, bartsch g, descotes j, heyns c, mcaninch j, et al. evaluation and management of renal injuries: consensus statement of the renal trauma subcommittee. bju international. 2004;93(7):937-54. 11. wright jl, nathens ab, rivara fp, wessells h. renal and extrarenal predictors of nephrectomy from the national trauma data bank. the journal of urology. 2006;175(3):970-5. 12. holmes jf, wisner dh, mcgahan jp, mower wr, kuppermann n. clinical prediction rules for identifying adults at very low risk for intra-abdominal injuries after blunt trauma. annals of emergency medicine. 2009;54(4):57584. 13. jones ts, stovall rt, jones el, knepper b, pieracci fm, fox cj, et al. a negative urinalysis is associated with a low likelihood of intra-abdominal injury after blunt abdominal trauma. the american journal of surgery. 2017;213(1):69-72. 14. sabzghabaei a, shojaee m, safari s, hatamabadi hr, shirvani r. the accuracy of urinalysis in predicting intraabdominal injury following blunt traumas. emergency. 2016;4(1):11. 15. moustafa f, loze c, pereira b, vaz m, caumon l, perrier c, et al. assessment of urinary dipstick in patients admitted to an ed for blunt abdominal trauma. the american journal of emergency medicine. 2017;35(4):628-31. 16. olthof dc, joosse p, van der vlies ch, de reijke tm, goslings jc. routine urinalysis in patients with a blunt abdominal trauma mechanism is not valuable to detect urogenital injury. emerg med j. 2015;32(2):119-23. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e58 rev i ew art i c l e the preparedness of hospital emergency departments for responding to disasters in iran; a systematic review and meta-analysis mosayeb kazemzadeh1, elham shafiei2, katayoun jahangiri3, kosar yousefi2, ali sahebi3∗ 1. msc in health care management, ilam university of medical sciences, ilam, iran. 2. clinical research development unit, shahid mostafa khomeini hospital, ilam university of medical sciences, ilam, iran. 3. department of health in disasters and emergencies, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. received: august 2019; accepted: september 2019; published online: 8 october 2019 abstract: introduction: hospitals are the most important infrastructures of any society. the hospital emergency department is one of the most important wards of hospitals in response to disasters. the purpose of this study was to evaluate the preparedness of hospital emergency departments in response to disasters in iran via a systematic review and meta-analysis. methods: this study was a systematic review and meta-analysis. the literature search was conducted in the national and international databases including sid, magiran, irandoc, google scholar, medline, scopus, and isi. valid persian and english keywords were used to extract articles related to the preparedness of hospital emergency departments in response to disasters. the strobe checklist was used to evaluate the quality of the articles, and the i2 index was used to assess heterogeneity among the studies. statistical analyses were conducted using stata14 software. results: in this study, 185 articles were initially recruited. meta-analysis was finally performed on 4 articles selected based on inclusion criteria. the analysis included a total of 51 hospitals in iran. according to our results, the mean preparedness of hospital emergency departments in response to disasters was calculated as 54.64% (95% ci = 41.15-68.13, i2 = 0.0%; p = 0.727). conclusion: the results of this study showed that the average level of preparedness of hospital emergency departments in iran to respond to disasters was moderate to high. therefore, planning and actions should be considered based on the guidelines and accreditation standards to enhance the preparedness of hospital emergency departments in response to disasters. keywords: disasters; disaster medicine; emergency service, hospital; meta-analysis as topic cite this article as: kazemzadeh m, shafiei e, jahangiri k, yousefi k, sahebi a. the preparedness of hospital emergency departments for responding to disasters in iran; a systematic review and meta-analysis. arch acad emerg mede. 2019; 7(1): e58. 1. introduction hospitals are among the most important infrastructures of any society. the constant activity of hospitals is essential for providing health services to the injured, both in normal conditions and in disasters (1). in addition to inflicting individuals, disasters have many impacts on the functional, structural and non-structural components of hospitals (2). hospital preparedness is a part of disaster management cycle. dis∗corresponding author: ali sahebi; department of health in disasters and emergencies, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. tel: 00989183434703, email: ali.sahebi@sbmu.ac.ir aster management preparedness consists of 9 components, the most important of which is planning. planning includes policies and programs to minimize disaster consequences. hospitals need to remain fully operational during disasters, and the assessment of hospital readiness is essential to ensure this issue (3). studies have reported moderate levels of structural, non-structural and functional safety in most iranian hospitals to respond to disasters. therefore, there is a need for proper planning and actions to improve the hospital safety level (4). a study conducted on 224 hospitals in iran in 2014 showed that the majority (54.5%) of iran’s hospitals had high vulnerability to disasters (5). among hospital wards, the emergency department is a key section in response to disasters. this is because emergency departments play a vital this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. kazemzadeh et al. 2 role in providing 24-hour acute care services to outpatients, inpatients, and those in immediate need for assistance (6). the personnel of emergency departments are hospital’s first responders to disasters and therefore, need to be appropriately prepared (7). the emergency department is the gateway for patients to enter the hospital. on the other hand, hospitals face a wide range of disasters and are responsible for responding to a variety of emergencies ranging from traffic accidents to terrorist attacks. hence, the preparedness of emergency department should not be neglected facing such incidents (8). at the time of disasters, the efficiency of emergency departments to manage mass casualty incidents (mci) depends on the availability and adequacy of human and financial resources (9). the purpose of this study was to evaluate the preparedness of hospital emergency departments in iran for responding to disasters via a systematic review and meta-analysis. 2. methods: the present study was conducted based on the guidelines of preferred reporting items for systematic reviews and metaanalyses (prisma) (10). to prevent bias, search, selection of studies, quality evaluation and data extraction were conducted by two researchers, independently in each stage. an agreement on the obtained data was finally achieved through group discussions. 2.1. search strategy the electronic search was conducted in irandoc, sid, magiran, scopus, pubmed (medline), embase, and web of science databases and manual search was done in google scholar using valid english keywords and their persian equivalents. the keywords included emergency ward, emergency unit, emergency room, hospital, response, emergency preparedness, emergency readiness, disaster, hospital emergency preparedness, and iran. the keywords were combined using (and) and (or) operators. the search strategy in pubmed used the following terms: ((((("civil defense"[mesh terms] or ("civil"[all fields] and "defense"[all fields]) or "civil defense"[all fields] or ("emergency"[all fields] and "preparedness"[all fields]) or "emergency preparedness"[all fields]) or (("emergencies"[mesh terms] or "emergencies"[all fields] or "emergency"[all fields]) and readiness[all fields])) and response[all fields]) and ("disasters"[mesh terms] or "disasters"[all fields] or "disaster"[all fields])) and ("hospitals"[mesh terms] or "hospitals"[all fields] or "hospital"[all fields]) and ("iran"[mesh terms] or "iran"[all fields])) . the timespan of gathering studies was limited to the end of july 2019. 2.2. inclusion criteria the inclusion criterion was descriptive cross-sectional studies that reported the rate of preparedness of emergency departments of iranian hospitals in response to disasters based on the checklist presented by the world health organization (who) (11). the who hospital emergency response checklist consists of 9 sections and 90 questions. the average overall preparedness score ranged from 0 to 100. the mean scores of 0-20, 2140, 41-60, 61-80 and 81-100 indicated very poor, poor, moderate, good and excellent readiness, respectively (12). studies in both english and persian were included. 2.3. exclusion criteria studies evaluating the preparedness or safety of hospitals in response to disasters as well as those evaluating the preparedness of emergency departments using tools other than the who instrument were excluded. 2.4. qualitative assessment the quality assessment of the studies was performed using the standard 22-item strobe checklist (13). the minimum and maximum obtainable scores using this checklist were 0 and 44, respectively. studies that acquired a minimum score of 16 were selected for meta-analysis. 2.5. data extraction initially, articles with unrelated titles were removed and then the abstracts and full texts of related articles were reviewed according to the inclusion criteria. the required data was extracted from the included articles using a pre-prepared checklist. the collected data included the first author, the location of study, the year of study publication, type of the study, number of evaluated hospitals, instruments used in the study, and finally the mean level of emergency department preparedness in response to disasters. 3. statistical analysis since the average level of preparedness of hospital emergency department in response to disasters was extracted based on the number of evaluated hospitals, binomial distribution was used to calculate the variance of each study. the weighted average was used to combine the preparedness levels in different studies. each study was weighted inversely corresponding to its variance. the heterogeneity index of studies was calculated as 0.0%, which was in the range of low heterogeneity indices (i.e. i2 indices <25%, 25 to 75%, and >75% indicate low, medium and high heterogeneities, respectively) (14). therefore, the fixed effects model was used for meta-analysis. in the present study, egger’s test was conducted to evaluate the possibility of publication bias. the data were analyzed using stata software (version 14). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e58 figure 1: prisma flow diagram of the study. table 1: the characteristics of the selected studies in meta-analysis first author place year study type hospitals* instrument quality mean % yousefli (12) ghazvin 2014 cs 6 who good 70.72 hasanpoor(20) karaj 2015 cs 13 who good 44.17 janati (21) tabriz 2018 cs 18 who good 54.26 seyedin (22) tehran 2018 cs 14 who good 56.93 *: number of hospitals. cs: cross-sectional, who: world health organization checklist. 4. results: in the initial search, 185 related studies were identified. of these, 181 studies were excluded due to not fulfilling the inclusion criteria. finally, 4 cross-sectional studies evaluating 51 hospitals between 2015 and 2018 entered quality assessment and meta-analysis. figure 1 shows the process of study selection. finally, 4 studies with good quality entered the meta-analysis. all the included studies used the hospital emergency response checklist presented by who. table 1 displays the general specifications and the data extracted from each study. according to our results, the overall preparedness of emergency departments of iranian hospitals in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. kazemzadeh et al. 4 figure 2: the forest plot of the overall and individual percentages of emergency department preparedness of iranian hospitals for responding to disasters with 95% confidence interval. response to disasters was 54.64% (95% ci = 41.15-68.13, i2 = 0.0%, p = 0.727) (figure 2). the highest and lowest levels of preparedness were reported in the studies of yousefli et al. in qazvin and hasanpoor et al. in karaj, respectively. the result of egger’s test showed that the effect of publication bias was not significant (p = 0.396). 5. discussion: in the present review, cross-sectional studies reporting the preparedness of emergency departments in response to disasters in 51 iranian hospitals were analyzed. these studies used the standard checklist developed by the who. overall, the preparedness of hospital emergency departments in response to disasters was 54.64% (95% ci = 41.15-68.13, i2 = 0.0%, p = 0.727) indicating a moderate to high level of preparedness. in a study in 2016, asefzadeh et al. (4) showed that overall preparedness for facing disasters was at moderate level in hospitals in iran. the overall safety level of ilam health centers in 2016 was estimated as 22.79%(15). the results of a study by jalali et al. comparing hospital disaster preparedness between iran and sweden showed that swedish hospitals were at level "a", while iranian hospitals attained level "b". there was no relationship between hospital readiness level and neither the hospital’s size or affiliation. however, the level of hospital readiness was significantly related to the social and economic levels of each country. furthermore, poor hospital readiness was due to the lack of contingency plans and the inadequacy of resources (16). considering the vital role of hospitals in treating the injured and reducing mortality in disasters, hospitals should be prepared to respond to disasters regardless of the economic status of each country. the results of another study by amiri et al. (17) showed that the hospital preparedness in response to disasters was at moderate level in 53 hospitals in northern iran. in the recent report, it was highlighted that educational programs, hospital resilience, drills, and exercises significantly contributed to improving hospital readiness. in a study, aladhrai et al. examined the readiness of yemen hospitals between 2011 and 2013 using the who hospital emergency response checklist and showed that no significant improvement was made in yemen hospitals preparedness against disasters during this period. in fact, the recent report revealed poor performance of all elements that were important for hospital preparedness such as management, surge capacity, and safety. this fact highlights the importance of implementing strategic plans, guidelines, and procedures by health authorities to promote disaster preparedness (18). the results of a study in 2016 by ingrassia et al. who evaluated the response to disaster of emergency departments at 15 hospitals in italy showed that 12 hospitals were inadequately prepared. based on the who hospital emergency response checklist, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e58 the average preparedness level was lower than normal in the evaluated hospitals (19). factors affecting the preparedness level of emergency departments included staff, equipment, and systems (8). following disasters, the emergency departments of hospitals suddenly become overcrowded due to mass casualties, so they must be prepared to respond to the situation. the results of several studies showed that the preparedness of hospitals to respond to disasters in iran was at moderate level. therefore, given the high incidence of disasters in iran, health policymakers should plan appropriate strategies and take adequate measures to improve disaster preparedness at all management levels. 6. limitations there were very few studies that reported the status of hospital emergency response to disasters using the who checklist. 7. conclusion according to the findings of the present review, the overall preparedness level of emergency departments of iranian hospitals in response to disasters was moderate to high. in addition, the level of hospital preparedness in response to disasters was also moderate in iran. therefore, given the high incidence of disasters in iran, health policymakers should take appropriate actions and implement required plans at all management levels using guidelines and accreditation standards to enhance the preparedness of hospital emergency departments in response to disasters. 8. appendix 8.1. acknowledgements we thank all the colleagues and researchers who contributed to the present review by publishing their results. 8.2. authors contributions study design: mosayeb kazemzadeh and ali sahebi systematic search, study selection, and quality assessment: elham shafiei, kosar yousefi statistical analyses and interpretation of data: ali sahebi, elham shafiei drafting of the manuscript: katayoun jahangiri and mosayeb kazemzadeh the final version of the manuscript was accepted by all authors. authors orcids mosayeb kazemzadeh: 0000-0003-0299-5833 elham shafiei: 0000-0001-5689-5235 katayoun jahangiri: 0000-0003-2061-1418 kosar yousefi: 0000-0002-7501-9238 ali sahebi: 0000-0003-4662-8998 8.3. funding support none. 8.4. conflict of interest the authors do not have any conflict of interest to declare. references 1. jahangiri k, izadkhah yo, lari a. hospital safety index (hsi) analysis in confronting disasters: a case study from iran. international journal of health system and disaster management. 2014;2(1):44. 2. ghafouri rr, hosseini sm, pouraghaei m. are our hospitals safe against disasters? an evaluation of hospital safety index in tabriz, iran. journal of analytical research in clinical medicine. 2018;6(3):139-44. 3. nekoie-moghadam m, kurland l, moosazadeh m, ingrassia pl, della corte f, djalali a. tools and checklists used for the evaluation of hospital disaster preparedness: a systematic review. disaster medicine and public health preparedness. 2016;10(5):781-8. 4. asefzadeh s, rajaee r, ghamari f, kalhor r, gholami s. preparedness of iranian hospitals against disasters. biotechnology and health sciences. 2016;3(3):1-6. 5. ardalan a, kandi m, talebian mt, khankeh h, masoumi g, mohammadi r, et al. hospitals safety from disasters in ir iran: the results from assessment of 224 hospitals. plos currents. 2014;6. 6. cimellaro gp. a model to evaluate disaster resilience of an emergency department. urban resilience for emergency response and recovery: springer; 2016. p. 361-87. 7. paganini m, borrelli f, cattani j, ragazzoni l, djalali a, carenzo l, et al. assessment of disaster preparedness among emergency departments in italian hospitals: a cautious warning for disaster risk reduction and management capacity. scandinavian journal of trauma, resuscitation and emergency medicine. 2016;24(1):101. 8. marzaleh ma, rezaee r, rezaianzadeh a, rakhshan m, hadadi g, peyravi m. emergency department preparedness of hospitals for radiation, nuclear accidents, and nuclear terrorism: a qualitative study in iran. iranian red crescent medical journal. 2019(in press). 9. gul m, guneri af. simulation modelling of a patient surge in an emergency department under disaster conditions. croatian operational research review. 2015;6(2):429-43. 10. moher d, liberati a, tetzlaff j, altman dg. preferred reporting items for systematic reviews and meta-analyses: the prisma statement. international journal of surgery (london, england). 2010;8(5):336-41. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. kazemzadeh et al. 6 11. bortolin m, s. sorensen b, d. zane r, e. wante b, b. rao m, rockenschaub g. hospital emergency response checklist an all-hazards tool for hospital administrators and emergency managers supported by the european commission together for health2010. 12. yousefli m, asefzadeh s, partovishayan z. evaluation of emergency wards readiness for responding to disasters and emergencies at hospitals of qazvin university of medical sciences according to world health organization model 2012. 2. 2014;6(2):0-. 13. vandenbroucke jp, von elm e, altman dg, gãÿtzsche pc, mulrow cd, pocock sj, et al. strengthening the reporting of observational studies in epidemiology (strobe): explanation and elaboration. international journal of surgery. 2014;12(12):1500-24. 14. yousefi k, adibi-larijani h, golitaleb m, sahebi a. knowledge, attitude and performance associated with disaster preparedness in iranian nurses: a systematic review and meta-analysis. advanced journal of emergency medicine. 2019. 15. jahangiri k, rostami n, sahebi a. challenges of utilizing the primary health safety index tool for assessing the vulnerability of healthcare centers to disasters. advanced journal of emergency medicine. 2019. 16. djalali a, castren m, khankeh h, gryth d, radestad m, ãűhlen g, et al. hospital disaster preparedness as measured by functional capacity: a comparison between iran and sweden. prehospital and disaster medicine. 2013;28(5):454-61. 17. amiri m, raei m, nasrollahpour shirvani sd, mohammadi gr, afkar a, jahani-tiji m, et al. preparedness of affiliated hospitals of universities in north of iran to confront disasters in the year 2011. hospital. 2013;12(1):1928. 18. aladhrai sa, djalali a, della corte f, alsabri m, el-bakri nk, ingrassia pl. impact of the 2011 revolution on hospital disaster preparedness in yemen. disaster medicine and public health preparedness. 2015;9(4):396-402. 19. ingrassia pl, mangini m, azzaretto m, ciaramitaro i, costa l, burkle jf, et al. hospital disaster preparedness in italy: a preliminary study utilizing the world health organization hospital emergency response evaluation toolkit. minerva anestesiologica. 2016;82(12):1259-66. 20. hasanpoor e, nazari m. hospital emergency response of iran’s hospitals against disasters: a case study in karaj. journal of hospital. 2015;4. 21. janati a, sadeghi-bazargani h, hasanpoor e, sokhanvar m, haghgoshyie e, salehi a. emergency response of iranian hospitals against disasters: a practical framework for improvement. disaster medicine and public health preparedness. 2018;12(2):166-71. 22. seyedin sh, hasanpoor e, hasanzadeh e, sheikhychaman m. assessment of hospital emergency response against disasters hospitals of iran university of medical siences: 2017. health_based research. 2018;4(2):159-67. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: statistical analysis results: discussion: limitations conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e4 or i g i n a l re s e a rc h characteristics and outcome of abdominal aortic aneurysm in emregncy department; a 10-year crosssectional study mohammad mehdi forouzanfar1, fatemeh barazesh1, behrooz hashemi1, saeed safari2,1∗ 1. emergency department, shohadye tajrish hospital, shahid behehsti university of medical sciences, tehran, iran. 2. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. received: october 2019; accepted: december 2019; published online: 25 january 2020 abstract: introduction: abdominal aortic aneurysm (aaa, triple a) is one of the less common but important causes of abdominal pain. this study aimed to evaluate the characteristics and outcome of patients presenting to emergency department with triple a. methods: in this retrospective cross-sectional study, all cases with confirmed triple a, who were presented to the emergency department of shohadaye tajrish hospital, tehran, iran from 2006 to 2017 (10 years) were enrolled using census sampling method. results: 500 cases with the mean age of 68.11 ± 11.98 (25 94) years were studied (84% male). the mean duration of symptoms was 2.32 ± 9.58 months and mean aneurysmal size was 63.91 ± 20.08 mm. in 4 (0.8%) cases, atrial fibrillation (af) was found during cardiac monitoring. patients stayed in the hospital for an average of 7.06 ± 6.32 days. aneurysmal leak was seen in 130 (26%) cases based on abdominal computed tomography (ct) scan findings. 369 (73.8%) cases underwent aneurysmorrhaphy, 126 (25.2%) were treated with non-surgical approaches, and 5 (1%) underwent grafting. 104 (20.8%) died and 396 (79.2%) were treated successfully. older age (p = 0.017), shock state at the time of presentation (p < 0.0001), leakage of aneurysm (p < 0.001), larger size of aneurysm (p = 0.024), and aneurysmorrhaphy (p < 0.001) were among the factors significantly associated with mortality. conclusion: based on the findings, the most frequent presenting symptom of patients was abdominal pain. the mortality rate of this series was 21% and older age, shock state, leakage of aneurysm, larger size of aneurysm, and performing aneurysmorrhaphy were among the factors significantly associated with mortality. keywords: aortic aneurysm, abdominal; abdominal pain; iliac aneurysm; outcome assessment cite this article as: forouzanfar m m, barazesh f, hashemi b, safari s. characteristics and outcome of abdominal aortic aneurysm in emregncy department; a 10-year cross-sectional study. arch acad emerg med. 2020; 8(1): e4. 1. introduction abdominal aortic aneurysm is a progressive abnormal local dilatation due to gradual aorta wall weakness (1). it is defined as increase in the mean diameter of abdominal aorta by twice the standard error of mean, and has a prevalence rate of 0.5 to 7.2 percent in men and 1 to 1.3 percent in women (2, 3). abdominal aortic aneurysm is usually asymptomatic until rupture (2). the risk of spontaneous rupture in these patients depends on the aortic diameter with rates of less than 0.5%, 1%, 11%, and 26% in cases with diameter less than 4 cm, 4-5 cm, 5-6 cm, and 6-7 cm, respectively (4). nearly 50 ∗corresponding author: saeed safari; emergency department, shohadye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. tel: 00989128251535, email: safari266@gmail.com | s.safari@sbmu.ac.ir to 90 percent of patients with aneurysmal rupture die before surgery, especially elderly men (5). also, the postoperative mortality rate is more than forty percent (6). prompt diagnosis and elective surgery would decrease the mortality rate to less than six percent (7). postoperative 30-day mortality rate in elective cases is 5 to 8 percent (8). considering the high mortality and morbidity rates in cases with abdominal aortic aneurysm and importance of early diagnosis to decrease the burden of the problem and noting the increase in frequency of aneurysm due to increased life longevity and higher rate of atherosclerotic diseases (9-14), this study aimed to evaluate the characteristics and outcome of patients with abdominal aortic aneurysm presenting to emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m m. forouzanfar et al. 2 2. methods 2.1. study design and setting in this retrospective cross-sectional study, patients with abdominal aortic aneurysm presenting to emergency department of shohadaye tajrish hospital, tehran, iran, from 2006 to 2017 (10 years) were studied. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.msp.rec.1396.189). researchers adhered to principles of helsinki decleration regarding the ethical issues in biomedical studies. 2.2. participants all patients with confirmed abdominal aortic aneurysm, who had presented to the emergency department during the study period, were enrolled using census sampling method. patients with an incomplete medical profile and those discharged against medical advice were excluded. there was not any age or sex limitation. 2.3. data gathering data were extracted from patients’ medical profiles using predesigned checklists containing demographic data (age, gender), presenting chief complaint, medical history, family history of aneurysm, characteristics of aneurysm (location, size), presence or absence of leakage based on computed tomography (ct) scan findings, and treatment approach, as well as outcome (mortality). a third year emergency medicine resident was responsible for data gathering. 2.4. statistical analysis data analysis was done using spss version 21.0 statistical software. findings were presented as mean ± standard deviation or frequency (%) for numerical and categorical variables, respectively. the utilized tests were chi-square, independent-sample-t test, and fisher’s exact test. p values less than 0.05 were considered statistically significant. 3. results 3.1. baseline characteristics of patients 500 cases with the mean age of 68.11 ± 11.98 (25 94) years were studied (84% male). table 1 shows the baseline characteristics of studied patients. anatomical location of aneurysm was abdominal aorta in 468 (93.6%) cases, abdomino-thoracic aorta in 28 (5.6%) cases, and iliac artery in 4 (0.8%) cases. the most frequent chief complaint of patients at the time of presenting to ed was abdominal pain (73.8%). the mean duration of symptoms was 2.32 ± 9.58 months and mean aneurysmal size was 63.91 ± 20.08 mm. in 4 (0.8%) cases, atrial fibrillation (af) was found during cardiac monitoring. table 1: baseline characteristics of studied patients variables frequency (%) gender male 412 (82.4) female 88 (17.6) presenting cheif complaint abdominal pain 369 (73.8) shock state 30 (6.0) limb ischemia 40 (8.0) chest pain 22 (4.4) others 39 (7.8) medical history cerebrovascular accident 44 (8.8) hypertension 258 (51.6) smoking 169 (33.8) dyslipidemia 57 (11.4) diabetes mellitus 50 (10.0) ischemic heart disease 173 (34.6) chronic kidney disease 23 (4.6) abdominal surgery 28 (5.6) family history of aneurysm no 497 (99.4) yes 3 (0.06) location of aneurysm abdominal aorta 468 (93.6) iliac artery 4 (0.8) thoracic aorta 28 (5.6) leakage of aneurysm no 368 (79.2) yes 130 (20.8) 3.2. outcomes patients stayed in the hospital for an average of 7.06 ± 6.32 days. aneurysmal leak was seen in 130 (26%) cases based on abdominal ct scan findings. 369 (73.8%) cases underwent aneurysmorrhaphy, 126 (25.2%) were treated with nonsurgical approaches, and 5 (1%) underwent grafting. 104 (20.8%) died and 396 (79.2%) were treated successfully. older age (p = 0.017), shock state at the time of presentation (p < 0.0001), leakage of aneurysm (p < 0.001), larger size of aneurysm (p = 0.024), and aneurysmorrhaphy (p < 0.001) were among the factors significantly associated with mortality (table 2). 4. discussion based on the findings, the most frequent presenting symptom of patients was abdominal pain. the mortality rate of this series was 21% and older age, shock state, leakage of aneurysm, larger size of aneurysm, and performing aneurysmorrhaphy were among the factors significantly associated with mortality. mirsharifi et al. (9) assessed 240 elderly patients using abdominal ultrasonography and incidentally found aorta aneurysm in 10% with mean diameter of 3.9 cm. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e4 table 2: correlation between baseline characteristics of patients and mortality variables survived (n = 396) died (n = 104) p value gender male 329 (79.9) 83 (20.1) 0.435 female 67 (76.1) 21 (23.9) age (year) mean ± sd 67.4 ± 11.8 70.7 ±12.3 0.017 shock state* no 380 (80.9) 90 (19.1) < 0.0001 yes 16 (53.3) 14 (46.4) type of surgery not surgical 119 (94.4) 7 (5.6) aneurysmorrhaphy 272 (73.2) 97 (26.3) < 0.001 grafting 5 (100.0) 0 (0.0) leakage of aeurysm no 334 (90.8) 34 (9.2) < 0.001 yes 60 (46.2) 70 (53.8) location of aneurysm abdominal aorta 370 (79.1) 98 (20.9) iliac artery 3 (75.0) 1 (25.0) 0.907 thoracic aorta 23 (82.1) 5 (17.9) medical history no 78 (80.4) 19 (19.6) 0.743 yes 318 (78.9) 85 (21.1) duration of symptom (month) mean ± sd 1.9 ± 3.7 2.04 ± 5.4 0.881 aneurysm size (mm) mean ± sd 62.4 ±18.4 71.6 ± 21.9 0.024 duration of hospital stay mean ± sd 7.4 ± 5.8 5.7 ± 7.6 0.014 data are presented as frequency (%) or mean ± standard deviation (sd). *: at the time of presenting to emergency department. kuivaniem et al. (10) reported that smoking and family history are the most important risk factors for abdominal aortic aneurysm. they also reported that mortality rate ranged from 50 to 80 percent, whereas it was only 20 percent in our study. chabok et al. (11) assessed 50,000 female subjects from the general population and reported that 82 subjects had abdominal aortic aneurysm and also stated that smoking, hypertension, older age, ischemic heart disease (ihd), and stroke were its main risk factors. tang et al. (12) assessed 15729 patients and reported that 5.5% had abdominal aortic aneurysm, which was more common among men, smokers, and those with dyslipidemia as shown in our study, especially about the effects of gender and smoking. yuan et al. (13) assessed 465 patients and reported hypertension, smoking, and dyslipidemia as the main risk factors for abdominal aortic aneurysm, which is similar to our results, especially regarding the first two factors. giribono and colleagues (14) assessed nine cases with abdominal aortic aneurysm, 4 of which required endovascular surgery and all were successful. but in our study, twenty percent of the patients died, especially cases under aneurysmorrhaphy. assessment of factors affecting the outcome is important for being able to predict the prognosis in patients with abdominal aortic aneurysm. in the current study, about 80% of the cases were discharged with good outome. considering the factors significantly associated with mortality in this study (older age, shock state, leakage of aneurysm, larger size of aneurysm, and performing aneurysmorrhaphy), it seems that performing prophylactic abdominal ultrasonography in high risk subjects such as smokers and hypertensive patients could be helpful in detection of cases in younger age and with stable situation. controlling the risk factors and planning for management before patients show symptoms and face a critical situation seems to be a logical strategy to reduce mortality. 5. limitations retrospective study design, missing data, not following the patients, and being a single center study were among the most important limitations of this study. 6. conclusion based on the findings, the most frequent presenting symptom of patients was abdominal pain. the mortality rate of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m m. forouzanfar et al. 4 this series was 21% and older age, shock state, leakage of aneurysm, larger size of aneurysm, and performing aneurysmorrhaphy were among the factors significantly associated with mortality. 7. declarations 7.1. acknowledgements all efforts of emergency department and documentary unit staff of shohadaye tajrish hospital are appritiated. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids mohammad mehdi forouzanfar: 0000-0003-0626-8545 behrooz hashemi: 0000-0002-5077-8545 saeed safari: 0000-0002-7407-1739 7.3. funding/support there was no funding and support. 7.4. conflict of interest we had no conflict of interest. references 1. lo rc, schermerhorn ml. abdominal aortic aneurysms in women. journal of vascular surgery. 2016;63(3):839-44. 2. kontopodis n, lioudaki s, pantidis d, papadopoulos g, georgakarakos e, ioannou cv. advances in determining abdominal aortic aneurysm size and growth. world journal of radiology. 2016;8(2):148-58. 3. gianfagna f, veronesi g, bertu l, tozzi m, tarallo a, ferrario m, et al. prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the risk of cardiovascular diseases and abdominal aortic aneurysm in varese (rocav ) population based study. bmc cardiovascular disorders. 2016;16(1):243. 4. sakalihasan n, limet r, defawe od. abdominal aortic aneurysm. the lancet. 2005;365(9470):1577-89. 5. ogata t, mackean gl, cole cw, arthur c, andreou p, tromp g, et al. the lifetime prevalence of abdominal aortic aneurysms among siblings of aneurysm patients is eightfold higher than among siblings of spouses: an analysis of 187 aneurysm families in nova scotia, canada. journal of vascular surgery. 2005;42(5):891-7. 6. visser p, akkersdijk g, blankensteijn j. in-hospital operative mortality of ruptured abdominal aortic aneurysm: a population-based analysis of 5593 patients in the netherlands over a 10-year period. european journal of vascular and endovascular surgery. 2005;30(4):359-64. 7. heller ja, weinberg a, arons r, krishnasastry k, lyon rt, deitch js, et al. two decades of abdominal aortic aneurysm repair: have we made any progress? journal of vascular surgery. 2000;32(6):1091-100. 8. prinssen m, verhoeven el, buth j, cuypers pw, van sambeek mr, balm r, et al. a randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. new england journal of medicine. 2004;351(16):1607-18. 9. mirsharifi r, zhand n, shahriyarian s, meysamie a, mirsharifi a, aminian a. the prevalence of abdominal aortic aneurysm in iranian male population over 65 years old. tehran university medical journal. 2011;69(5):322-6. 10. kuivaniemi h, ryer ej, elmore jr, tromp g. understanding the pathogenesis of abdominal aortic aneurysms. expert review of cardiovascular therapy. 2015;13(9):975-87. 11. chabok m, nicolaides a, aslam m, farahmandfar m, humphries k, kermani n, et al. risk factors associated with increased prevalence of abdominal aortic aneurysm in women. british journal of surgery. 2016;103(9):1132-8. 12. tang w, yao l, roetker ns, alonso a, lutsey pl, steenson cc, et al. lifetime risk and risk factors for abdominal aortic aneurysm in a 24-year prospective study: the aric study (atherosclerosis risk in communities). arteriosclerosis, thrombosis, and vascular biology. 2016;36(12):2468-77. 13. yuan h, han x, jiao d, zhou p, editors. a case-control study of risk factors of abdominal aortic aneurysm. the heart surgery forum; 2016. 14. giribono am, ferrara d, spalla f, narese d, bracale u, pecoraro f, et al. endovascular treatment of spontaneous isolated abdominal aortic dissection. acta radiologica open. 2016;5(12):2058460116681042. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e10 rev i ew art i c l e psychogenic non-epileptic seizures; a narrative review ameneh jafari1, mostafa rezaei tavirani2∗, mohsen parvareshi hamrah2, sanaz ahmadi karvigh3, haniyeh bashi zadeh fakhar4 1. student research committee, proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 3. department of neurology, sina hospital, tehran university of medical sciences, tehran, iran. 4. department of laboratory science,chalous branch,islamic azad iniversity,chalous,iran. received: november 2019; accepted: december 2019; published online: 20 january 2020 abstract: psychogenic non-epileptic seizures (pnes) are paroxysmal changes that mimic epileptic seizures, so often misdiagnosed and treated for epilepsy. pnes are considered a psychiatric illness, personality pathology, and experiential and behavioral manifestation of depression. despite studies over the past two decades, the pathological mechanisms of this disorder are unclear. in this paper, we critically review the current literature about the definition, epidemiology, diagnosis, treatment, related genes, and biomarkers of pnes and provide suggestions for future research. further studies are needed for more information and knowledge on pnes to determine the appropriate psychotherapies and development of clear treatment guidelines. keywords: seizures; epilepsy; psychogenic; biomarkers; conversion disorder cite this article as: jafari a, rezaei tavirani m, parvareshi hamrah m, ahmadi karvigh s, bashi zadeh fakhar h. psychogenic non-epileptic seizures; a narrative review. arch acad emerg med. 2020; 8(1): e10. 1. introduction psychogenic non-epileptic seizures (pnes) are defined as paroxysmal changes in behavior, consciousness and autonomic function that resemble epileptic seizures (es) but lack the electroencephalographic (eeg) signature of epileptic seizures [1-3]. pnes are characterized by disturbance of motor, autonomic, sensory, cognitive and/or emotional functions. the diagnosis of pnes is challenging and can take an average of 7 years between the manifestation of spells and definite diagnosis [4-6]. therefore, patients with pnes are often misdiagnosed and face delays in reaching a definite diagnosis, and consequently are exposed to unnecessary antiepileptic drugs, emergency treatment, and even hospital admissions and other complications caused by unnecessary treatments [2, 7, 8]. pnes, erroneously diagnosed as epileptic also have an economic impact. the cost of misdiagnosis and treatment for pnes is surprising. estimates suggest the cost of ∗corresponding author: mostafa rezaei tavirani, proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. tel: 00982122714248, e-mail:tavirani_m@yahoo.com intractable epilepsy to be about $ 231,432 per patient in 1995 [4]. considering the heterogeneity of patients with pnes, the etiology of this disorder is very diverse but some factors including trauma, neurological abnormalities, family dysfunction, stressful life events, and poor interpersonal skills and affect regulation, somatization, psychopathology, personality factors, and avoidant coping styles are identified as influential in development and maintenance of psychogenic nonepileptic seizures [3, 9, 10]. this review aimed to present an overview of existing research regarding the etiology, epidemiology, diagnosis, and management of pnes. 2. epidemiology to understand the impact of pnes, various aspects other than absolute frequency should be considered. it must be noted that patients with pnes are as disabled because they are treated as a patient with epilepsy, receive high medical care and are consequently at risk of iatrogenic harm [11]. epidemiological data on pnes are sparse and limited. one study from iceland, estimated the incidence of pnes as 1.4 per 100.000, with symptoms commonly emerging in young adulthood (20 to 40 years old) [12]. however, it is important to keep in mind that pnes can be detected at any age; this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. jafari et al. 2 for example, they are not rare in children and are described in the elderly. another study was demonstrated in ohio and calculated the mean incidence of pnes at around 3/100,000 [12]. approximately, 75% of patients with this condition are females, probably due to neurobiological, social and vulnerability differences [10]. overall, although patients with pnes do not fit with a single stereotype, younger women with a high level of mental health and history of past abuse are more likely to be among this patient group. prevalence of pnes is estimated in the range of one person per 30,000–50,000 or between 2-3.3 per 100,000 [13, 14]. some studies have suggested that epilepsy may increase the risk of pnes not only through biological mechanisms but also by experiencing or observing epileptic seizure cases, which may provide an opportunity for model learning [15]. 3. diagnosis early diagnosis of psychogenic non-epileptic seizures is very important, but unfortunately, the diagnosis is often delayed, and because of this, many patients are faced with the consequences of undesirable treatment [4, 12]. on the other hand, the diagnosis of pnes in the early phase may result in cost savings and reduce the burden on patients and the health care system [16]. quality of life in pnes patients is significantly lower than in patients with epilepsy, which is due to psychopathology and undesirable effects of antiepileptic drugs [17]. diagnosis of pnes poses particular challenges and pnes must be distinguished from other disorders, such as sleep disorders, migraine, hyperventilation, syncope, paroxysmal dyskinesia, movement disorders, transient ischemic attacks and myasthenia gravis, which are mediated by physiological or psychological causes [10]. an accurate clinical diagnosis of pnes is possible after history taking and direct observation of attacks by an epilepsy specialist in the majority of cases [10, 18]. the clinical and historical features that distinguish pnes from epileptic attacks are listed in table 1. some of the clinical features commonly found in people with epilepsy are often present in pnes. these include autonomic manifestations like tachycardia, incontinence, injury, flushing, sweating, nocturnal attacks and provocation of attacks by specific triggers such as flashing lights have often appeared to be a feature of epilepsy, but are commonly reported in pnes [19]. in addition to behavior during attacks, other characteristics of the patient’s behavior can provide some clues and warn physicians of the possibility of pnes. for instance, they are more likely to have attacks in medical settings. pnes patients also seem to have a distinct way of communicating and talking about the attacks that distinguishes them from patients with epilepsy [20, 21]. patients with pnes may be diagnosed with several psychiatric diseases including dissociative disorder, somatoform disorder, affective disorder, personality disorder, and other anxiety disorders [4]. accurate diagnosis and management of pnes requires experience, skill, the use of video eeg and collaboration among neurologists, psychiatrists, pediatricians, nursing staff and other professional colleagues [1]. approaches for diagnosis of pnes include epilepsy, eeg, symptom provocation, clinical history, and observation [22]. video-eeg monitoring is considered a diagnostic gold standard in evaluation of seizure-like events, particularly in differentiating between pnes and epileptic seizures [7, 12]. video-eeg is a highly specific and sensitive technique with a diagnostic yield of 50 to 60 percent. although it is a costly technique, due to the intrinsic complexity of this group of patients, videoeeg confirmation is often needed for definitive diagnosis of pnes. in addition to video-eeg, monitoring ictal eye closure and functional magnetic resonance imaging (fmri) might be useful methods for diagnosing patients with pnes [2]. since eeg is an expensive method, it is not available in many centers, it also requires long-term admission and is not able to capture an actual seizure episode for several times, so alternative and auxiliary methods and indirect biomarkers are needed for diagnosis, which we will explain subsequently. 3.1. biomarkers multiple studies suggested various biomarkers for differentiation between epileptic seizures (es) and pnes. evidence showed that prolactin (prl) values in es patient groups were significantly higher than patients with pnes [23-25]. results related to cortisol level are controversial. zhang and liu have demonstrated a typical pattern of pre-ictal decrease and postictal increase of cortisol in es, but there were no such changes in pnes [26-28]. in their study, bakvis et al. confirmed that pnes patients possess basal hypercortisolism, which positively correlated with both traumatic histories and threat vigilance [29, 30]. it is reported that a number of pituitary hormones such as thyrotropin-releasing hormone and growth hormone along with prl and cortisol increase in serum following es but not pnes [7, 31]. according to numerous studies, serum creatine kinase (ck) is the most promising candidate enzyme for differentiating es from pnes with a sensitivity of 75%, and specificity of 85.5% [31-33]. based on the evidence, raised serum creatine phosphokinase (cpk) level significantly correlates with the presence of a seizure as the cause of loss of awareness [34]. javali and colleagues reported that none of the patients with pnes showed elevation in either serum prl or cpk [34]. concerning other hormone candidates, ghrelin, nesfatin and brain-derived neurotrophic factor (bdnf) are important hormones that can be used as adjunct diagnostic tools for pnes [35, 36]. aydin et al. have found postictal serum and salivary nesfatin elevation in es patients compared to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e10 table 1: clinical and historical features suggested for diagnosis of psychogenic non-epileptic seizures (pnes)[10, 18] clinical features historical features observer’s ability to modify the patient’s motor activity associated (often multiple) psychiatric disorders avoidance behavior during seizures flurries of seizures or recurrent pseudo– status epilepticus that lead to multiple asynchronous limb movements emergency department visits or hospitalizations change in symptomatology high seizure frequency closed eyes during seizures or resisted eyelid opening history of sexual or physical abuse dystonic posturing (including opisthotonos) lack of concern or an excessive or exaggerated emotional response emotional or situational trigger for seizure onset multiple unexplained physical symptoms ictal crying, weeping no history of injury from seizures if tongue biting is present, usually the tip no response to antiepileptic drugs or a (not the side) of the tongue paradoxical increase in seizures with intermittent or waxing and waning motor activity antiepileptic drug treatment gradual onset of attacks personal, family, or professional experience with epilepsy non-physiological progression rhythmic pelvic movements seizures that occur only in the presence of others or only when the out of phase movements patient is alone side-to-side head movements those with pnes. additionally, they detected lower postictal serum ghrelin amounts in es patients compared to those who had pnes [37]. connolly and colleagues have demonstrated increased serum brain-derived neurotrophic factor (bdnf), a neurotrophin with important effects on neurogenesis and neuronal plasticity, in children with epilepsy; whereas lowered levels were detected in depressive disorder [38, 39]. lafrance et al. confirmed lower postictal bdnf in patients with es, similar to pnes patients; thereby, bndf is not specific in differentiating seizure types. there is a hypothesis that decreased serum bdnf in es and pnes is probably related to stress, not to seizure [40]. as we mentioned earlier, serious sexual, physical, or emotional abuse has been reported in childhood history of many pnes patients. studies showed that pnes patients experience physical injuries to the hypothalamic–pituitary–adrenal (hpa) axis. nearly 50% of people with pnes have psychological disorders related to trauma, including anxiety, depression and post-traumatic stress disorder (ptsd) [41]. following activation of hpa axis, adrenocorticotropic hormone (acth) is secreted into the blood stream, which induces the release of cortisol. ending the stress response is crucial because long-term activation of the sympathetic nervous system (sns) and hpa axis can lead to enduring health consequences such as autoimmune diseases and growth disorders [42]. however, changes in other signaling pathways can also be attributed to stress-related health problems in pnes patients. for instance, higher levels of testosterone and lower levels of oxytocin have been reported in women with a history of abuse and chronic stress [43]. in women, estradiol is lower during stressful conditions compared to normal situations [44]. moreover, increased amounts of prl have been observed in post-ictal events in epilepsy [41]. neuropeptide y (npy), another component of the sns, is an inhibitory neuromodulator in the brain that can control propagation of limbic seizures. in addition, npy’s interaction with cortisol helps individuals cope with stress and maintain health, while overexpression and decrease of npy are related to ptsd [41]. the role of npy in pnes remains unclear. decreased npy levels may contribute to the onset of pnes symptoms. studies have demonstrated lower levels of npy and cortisol and elevated plasma acth levels in pnes patients with or without exposure to abuse in comparison to healthy controls [41, 45]. cns, endothelial cells, and bone cells produce a member of the family of natriuretic peptide hormones called c-type natriuretic peptide (cnp) [46]. the concentration of cnp is very low in circulation and its half-life is also very short, about 3 minutes [47]. an amino-terminal fragment of cnp, nt-pro cnp, is more stable compared to its predecessor. ceylan m et al. reported lower amounts of post-ictal serum nt-procnp in es patients compared to pnes patients and healthy controls, regardless of gender [48]. they postulated that such a difference is associated with cnp-related neural mechanisms, such as increased blood-brain barrier permeability, altered microcirculation, and synaptic stabilization [48]. 4. associated factors pnes occur in a heterogeneous population of patients. no single mechanism or interfering factor has been identified for pnes in all patients. although past traumatic experience and physical or sexual abuses are a common feature and the main cause of pnes, numerous studies identified potential this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. jafari et al. 4 interacting factors in patients with pnes, including predisposing, precipitating and perpetuating factors. predisposing factors such as sexual abuse and physical and emotional neglect will lead to individual vulnerability and the risk of developing pnes [15, 21, 29]. precipitating factors can be divided into stressors or situations that would probably trigger attacks in patients with established pnes [15]. a wide variety of events, such as rape, death of or separation from family members or friends, job loss, injury, accidents, surgical procedures, natural disasters, tiredness, and relationship difficulties, seem to trigger the onset of pnes, because they occur days to months before the onset of seizures [22]. factors such as anxiety, anger, depression, and mistreatment have been considered as potentially preventable perpetuating factors [15, 21]. in summary, the insight of the patient, as well as external factors that can enhance their behavior can be affected by confirming the pnes. all of these factors play an important role in the onset or development of pnes, and should not be ignored. 5. management and treatment our knowledge remains limited to the best management strategies for pnes, and although several psychiatric interventions have been described, there is little evidence in this regard. this probably reflects the fact that pnes is not a disease entity but a symptom of a variety of basic psychiatric and psychological problems requiring a series of treatments [49]. in the initial phase of treatment (diagnosis delivery phase), effective communication with a neurologist is very important for a group of patients with pnes who often feel confused and irritated after diagnosis [50]. when the diagnosis of pnes is made, most patients are referred for psychological treatment. a wide variety of psychotherapeutic interventions including behavioral approaches, hypnosis, psycho-education, and family therapy have been proposed [4]. at the end of the second phase of treatment (engagement phase), patients will understand their diagnosis; no longer need other diagnostic evaluations elsewhere, start communicating with a mental health care provider, and actively participate in treatment [22]. the primary goal of the third phase of treatment (acute intervention phase) is to reduce the frequency of seizures, but improvement in psychiatric comorbidities, functional recovery, and quality of life is also desired [51]. treatment will be selected according to the unique circumstances of the patient with pnes and will help resolve his/her emotional and psychological causes. most patients with pnes have other psychiatric illnesses such as depression, anxiety, bipolar disorders, personality disorder, and many others. of all the various interventions, cognitive behavior figure 1: the main approaches for treatment of psychogenic nonepileptic seizures (pnes). therapy (cbt) significantly improved the range of clinical and psychological factors and was more effective in reducing attack frequency compared to standard medical care such as medication [52, 53]. psychological training, relaxation education, exposure to inevitable conditions and cognitive restructuring are common techniques in cbt [52, 53]. the final phase of the treatment (long-term interventions phase) is particularly relevant to the subgroup of pnes patients who will need ongoing care to achieve functional recovery [22, 51]. some suggested treatments for patients with psychogenic non-epileptic seizures are illustrated in figure 1. 6. conclusion pnes include paroxysmal changes in responsiveness, behaviors, consciousness or movements that look like epileptic seizures but lack electrophysiological epileptic changes. pnes are common among women and usually begin in young adolescence. diagnosis and treatment of these disorders are challenging. accurate diagnosis and management of pnes need video-eeg monitoring and a multidisciplinary collaborative approach among pediatricians, psychiatrists, neurologists, and other specialists. in addition to a videoeeg, biomarkers have indicated limited benefit in diagnosis of pnes. hyper-cortisolism, delayed ck/cpk release, lowered postictal serum and salivary nesfatin and elevated postictal serum ghrelin level are useful for differentiating pnes from es. furthermore, lower serum levels of bndf and npy are considered biomarkers for development of pnes. these this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e10 biomarkers are useful for detection of pnes among patients with seizure symptoms, and easier and less expensive than video-eeg. further studies are necessary to identify new biomarkers and psychopathological mechanisms for finding appropriate treatments for pnes in the future. 7. declarations 7.1. acknowledgements we thank the "student research committee" and "research & technology chancellor" in shahid beheshti university of medical sciences for their financial support. 7.2. authors contributions all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids mostafa rezaei tavirani: 0000-0003-1767-7475 7.3. funding support this study is extracted from a project funded by student research committee, shahid beheshti university of medical sciences, tehran, iran. 7.4. conflict of 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74(24): p. 1986-1994. 53. lafrance jr, w.c., et al., cognitive behavioral therapy for psychogenic nonepileptic seizures. 2009. 14(4): p. 591596. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction epidemiology diagnosis associated factors management and treatment conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e34 rev i ew art i c l e risks of novel coronavirus disease (covid-19) in pregnancy; a narrative review latif panahi1, marzieh amiri2, somaye pouy3∗ 1. master student of nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 2. department of emergency medicine, razi hospital, school of medicine, guilan university of medical sciences, rasht, iran. 3. phd student of nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. received: march 2020; accepted: march 2020; published online: 23 march 2020 abstract: introduction: the outbreak of the new coronavirus in china in december 2019 and subsequently in various countries around the world has raised concerns about the possibility of vertical transmission of the virus from mother to fetus. the present study aimed to review published literature in this regard. methods: in this narrative review, were searched for all articles published in various databases including pubmed, scopus, embase, science direct, and web of science using mesh-compliant keywords including covid-19, pregnancy, vertical transmission, coronavirus 2019, sars-cov-2 and 2019-ncov from december 2019 to march 18, 2020 and reviewed them. all type of articles published about covid-19 and vertical transmission in pregnancy were included. results: a review of 13 final articles published in this area revealed that covid-19 can cause fetal distress, miscarriage, respiratory distress and preterm delivery in pregnant women but does not infect newborns. there has been no report of vertical transmission in pregnancy, and it has been found that clinical symptoms of covid-19 in pregnant women are not different from those of non-pregnant women. conclusion: overall, due to lack of appropriate data about the effect of covid-19 on pregnancy, it is necessary to monitor suspected pregnant women before and after delivery. for confirmed cases both the mother and the newborn child should be followed up comprehensively. keywords: covid-19; pregnancy; infectious disease transmission, vertical; coronavirus; severe acute respiratory syndrome coronavirus cite this article as: panahi l, amiri m, pouy s. risks of novel coronavirus disease (covid-19) in pregnancy; a narrative review. arch acad emerg mede. 2020; 8(1): e34. 1. introduction coronaviruses are among the main human and animal pathogens (1). the covid-19 epidemic began in china and quickly spread to other countries and became a major health problem (2). the disease was first spread in wuhan, the capital of hubei province, china, and the quickly spread to other countries around the world, including iran (3-5). since the first case of covid-19 in wuhan, china, up to march 19th, 234073 people in the world have been infected with covid19 and 9840 people have died because of covid-19 infection (6-9). on january 30, 2020, the world health organization (who) ∗corresponding author: somaye pouy, phd student of nursing, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. email: somayepouy@gmail.com, tel: +989221538452 labeled the outbreak as a public health emergency of international concern (pheic). on february 12, 2020, who named the disease caused by the novel coronavirus "coronavirus disease 2019" (covid-19). a team of international experts, with a range of specializations, has tried to manage this outbreak (10, 11). pneumonia caused by covid-19 is a highly contagious and infectious disease declared a health emergency by the world health organization (11-13). the exact way of disease transmission has not yet been determined, but the researchers found that the virus spreads through respiratory droplets like the flu, and air precautions are very necessary given the lack of information in this area (14). with the spread of the coronavirus, concerns have been raised about its intrauterine transmission from mother to fetus in pregnant women (2, 3, 15). viral pneumonia is one of the leading causes of pregnancy deaths worldwide (16). important questions raised due to the spread of covid-19 inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 2 clude: are the symptoms of pneumonia in pregnant women different from those of non-pregnant women? how likely are maternal and neonatal mortality? does it cause pregnancy complications or premature birth? and how much covid19 is transmitted to the baby (3, 17)? given the importance of the issue and the lack of sufficient evidence, the present study aimed to review the published evidence in this regard. 2. methods this study is a narrative review designed to collect published literature and articles on intrauterine transmission of covid-19 from mother to fetus. in this review, we searched for all articles published in various databases including pubmed, scopus, embase, science direct and web of science using mesh-compliant keywords including covid-19, pregnancy, vertical transmission, coronavirus 2019, sars-cov-2 and 2019-ncov from december 2019 to march 11 2020 and then reviewed them. all original research studies, letters to the editor, and reviews published on the impact of covid19 on fetal health and intrauterine transmission of covid-19 were included. the title and abstract of all published articles were analyzed separately using specific keywords by two researchers, the relevant articles were collected, and their results were summarized and reported. 3. results 3.1. characteristics of included studies searching the databases using specific keywords yielded 913 articles. after elimination of duplicates and review of abstracts and titles, 15 of articles were deemed relevant. 3 of the 15 articles were excluded due to being written in chinese and finally 13 articles were included in the study. no original research on covid-19 has been published so far, and only five studies were designed as case study or case series. other published studies were in the form of correspondence, commentary or letters to the editor. characteristics of included studies are presented in table 1. 3.2. analysis of the reports a total of 37 pregnant mothers with covid-19 and 38 newborns (two were twins) were studied. the age range of mothers was 23-40 years. of these, 29 had cesarean delivery and 8 had normal delivery. of the 37 pregnant mothers, 7 reported preterm labor at 30-33 weeks of age and the rest had no preterm labor and all had delivery in the third trimester (between 34 and 40 weeks’ gestation). only one study reported that the neonate died after birth. of the 37 mothers, 6 had preterm labor, 6 had premature rupture of the membrane, 2 had abnormal amniotic fluid, and 2 had abnormal umbilical cord. none of the mothers needed mechanical ventilation after delivery and only received antiviral, antibiotic, and oxygen therapy through the nasal catheter. only one parturient woman required icu admission and oxygen through the venturi mask and her neonate was admitted to the nicu ward for monitoring. the most common infected mothers’ symptoms were fever, cough, and chest pain. on admission, the lungs of all mothers were normal, but chest ct scan reported unilateral and bilateral infiltrations. out of the 37 studied mothers, 2 had clinical manifestations of covid-19 during delivery, 2 showed symptoms after delivery and the rest of them had symptoms of covid-19 during hospitalization and prenatal delivery. chest ct scan was performed for all of them and the most commonly reported finding was ground glass opacity (ggo) with progressive to consolidations. in 35 mothers, chest ct scan before and after delivery revealed no changes, in four postpartum women chest ct scan results had improved and in one patient it had exacerbated. the most common laboratory finding was lymphocytopenia. no antiviral medications were given to mothers during pregnancy. all of the studied women gave birth to a healthy baby, with an apgar score of 8-10. no amniotic fluid abnormality, cyanosis, asphyxia, abortion, or congenital abnormalities at birth were reported. samples were taken from neonate’s throat, umbilical cord, amniotic fluid, stool, neonatal blood samples and breast milk of mother immediately after birth for screening of sarv-19 infection via sars-cov2 rt-pcr. regarding neonatal outcomes, no information is available on teratogenicity and transmission of infection via placenta in the first, second and third trimesters of pregnancy, during normal vaginal delivery and through breast milk. based on reported cases, all neonates with confirmed covid-19 had been infected after birth via cough of mother or other relatives, or through the infected environment and had an average time of symptom manifestation between 5 to 17 days after birth. the most common symptoms of covid-19 in the studied infants were tachypnea, milk regurgitation, vomiting, cough, fever, pneumothorax, liver disorders, thrombocytopenia, and pulmonary changes in chest ct scan. all infants born to mothers with covid-19 were fed formula. 4. discussion based on the findings of the present study, no original research has been carried out on the possibility of vertical transmission of covid-19 from mother to the fetus and it is essential to carry out effective research in this area. according to results of studies, infected or suspected mothers should be carefully monitored before and after delivery. they should avoid breastfeeding until it is confirmed that they are not infected with covid-19. also, mothers and their this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e34 table 1: screening performance characteristics of scoring systems in predicting re-bleeding risk in upper gastrointestinal bleeding author year country title key finding chen et al. (12) 2020 china clinical characteristics and intrauterine vertical transmission potential of covid-19 infection in nine pregnant women: a retrospective review of medical records ◦ covid-19 in pregnant woman can cause fetal distress but does not infect newborns. chua et al. (18) 2020 china from the frontlines of covid-19–how prepared are we as obstetricians: a commentary ◦ no evidence of intrauterine infection of covid-19 caused by vertical transmission for fetus. ◦ infected or suspect mothers should refrain from breastfeeding. ◦ all mothers infected with covid-19 should be monitored carefully during pregnancy and after delivery. liu et al. (17) 2020 china pregnancy and perinatal outcomes of women with covid-19 pneumonia: a preliminary analysis ◦ pregnancy and childbirth did not aggravate the course of symptoms or ct features of covid-19 pneumonia. liu et al. (16) 2020 china coronavirus disease 2019 (covid-19) during pregnancy: a case series ◦ no evidence to suggest the potential risk of intrauterine vertical transmission. lu et al. (19) 2020 china coronavirus disease (covid-19) and neonate: what neonatologist need to know ◦ there is currently no evidence of transplacental transmission of sarscov-2 from the mother to the newborn. mardani et al. (3) 2020 iran a controversial debate: vertical transmission of covid-19 in pregnancy ◦ neonates born to women with suspected or confirmed covid-19 infection should be isolated for at least two weeks after birth and not be breastfed. ◦if 2019-ncov infection is confirmed during pregnancy, both the mother and fetus should be followed up extensively. qiao et al. (2) 2020 china what are the risks of covid-19 infection in pregnant women? ◦there is not sufficient evidence about intrauterine vertical transmission. rasmussen et al. (4) 2020 usa coronavirus disease 2019 (covid-19) and pregnancy: what obstetricians need to know ◦fetal distress and preterm delivery were seen in some newborns. ◦the babies of all pregnant women with covid19 were tested for sars-cov-2 after delivery and had negative results. wang et al. (15) 2020 china a case of 2019 novel coronavirus in a pregnant woman with preterm delivery ◦ there is no evidence of fetus distress or neonatal infection with covid-19. ◦ covid-19 in pregnancy can be mild to severe and result in preterm delivery. zhu et al. (20) 2020 china clinical analysis of 10 neonates born to mothers with 2019-ncov pneumonia ◦ perinatal 2019-ncov infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. liang et al. (20) 2020 china novel corona virus disease (covid-19) in pregnancy: what clinical recommendations to follow? ◦ there is no evidence for vertical transmission of covid-19 in pregnant woman. ◦all mothers with covid-19 should be monitored carefully. faver et al. (21) 2020 china 2019-ncov epidemic: what about pregnancies? ◦infection with covid-19 in pregnant women can have adverse effects including miscarriage, fetal growth restriction, and preterm birth or death of the mother. schwartz et al. (22) 2020 china potential maternal and infant outcomes from coronavirus 2019-ncov (sars-cov-2) infecting pregnant women: lessons from sars, mers, and other human coronavirus infections ◦ there is limited knowledge regarding coronavirus infections that occur during pregnancy. ◦ previous experiences with coronavirus infections in pregnancy indicate that these agents are capable of causing adverse clinical outcomes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 4 neonates should be taken care of in isolated rooms in order to prevent neonatal transmission. mothers with confirmed covid-19 should be treated with antibiotics and antiviral drugs after childbirth (18). in this regard, a study by chen et al. in china on 9 pregnant mothers with covid-19 found that none of the newborns had postpartum complications such as covid-19 infection and prematurity (12). this finding is in line with the results of a previous study on sarscov-1 that was done by wong and colleagues (15). however, acourding to some studies, infection with covid-19 during pregnancy can cause complications for both the mother and the fetus; including preterm delivery, respiratory distress, fetal distress, coaglopathy accompanied by liver dysfunction and death of the mother. the newborn and the mother with confirmed covid-19 should be isolated in different rooms and be screened very carefully (4, 7, 21, 23). also, according to chen et al., the clinical symptoms of covid-19 in pregnant women were not significantly different from those of non-pregnant women, with common symptoms including chest pain, shortness of breath, fever and lethargy (12). also, liu et al. found that pregnancy and childbirth did not aggravate the course of symptoms or ct features of covid19 pneumonia (16). overall, due to lack of evidence, scientists and researchers could not confirm vertical transmission of covid-19 infection from placenta, during delivery and breast milk in the perinatal period (17). in some studies, evaluating both cesarean and normal vaginal delivery in mothers with covid-19 showed that neither type of delivery affected their newborns and all of the studied newborns were negative for covid-19 infection (12, 15, 16, 24). previously published studies have demonstrated that being affected with sars during perinatal period is associated with a high prevalence of harmful maternal and neonatal side effects including disseminated intravascular coagulopathy, abrupt abortion, preterm childbirth, intrauterine growth retard, neonatal intubation and need of newborn to be admitted to neonatal intensive care unit, and organ failure (17, 25). generally, our review of literature showed that pregnant women infected with covid-19 and their newborns had less problems than would be anticipated for those with sars-cov-1 infection. although the findings should be interpreted with percaution because of the small sample size, the results are mostly in line with the findings by zhu and colleagues (24) that was done on ten newborn who were born to mothers with covid19 pneumonia. also, the clinical manifastations reported in pregnant women with positive covid-19 are similar to those reported for non-pregnant women infected with covid-19 and relatively good clinical outcomes have been reported for covid-19 infection in pregnant women compared with sars-cov-1 infection (26, 27). more studies in this area are recommended. 5. declarations 5.1. acknowledgements the authors wish to thank all those who contributed to this study. 5.2. authors contributions latif panahi: study design, data collection, writing draft of study. marzieh amiri: study design, data collection, writing draft of study. somaye pouy: study design, data collection, writing manuscript, supervision of study. authors orcids latif panahi: 0000-0001-5157-2613 marzieh amiri: 0000-0002-1808-3815 somaye pouy: 0000-0003-3307-7840 5.3. funding support no fund was received for this study. 5.4. conflict of interest there is no conflict of interest. references 1. mcintosh k, hirsch ms, bloom a. coronavirus disease 2019 (covid-19). 2. qiao j. what are the risks of covid-19 infection in pregnant women? the lancet. 2020. 3. mardani m, pourkaveh b. a controversial debate: vertical transmission of covid-19 in pregnancy. neoscriber demo publisher. 4. rasmussen sa, smulian jc, lednicky ja, wen ts, jamieson dj. coronavirus disease 2019 (covid-19) and pregnancy: what obstetricians need to know. american journal of obstetrics and gynecology. 2020. 5. tavakoli a, vahdat k, keshavarz m. novel coronavirus disease 2019 (covid-19): an emerging infectious disease in the 21st century. ismj. 2020;22(6):432-50. 6. organization wh. coronavirus disease 2019 (covid-19) situation report – 60 2020 [updated march 16, 2020; cited 2020]. available from: https://www.who.int/emergencies/diseases/novelcoronavirus-2019/situation-reports/. 7. yang p, liu p, li d, zhao d. corona virus disease 2019, a growing threat to children? journal of infection. 2020. 8. yu a, wang z, ren w, wu z, hu z, li l, et al. epidemic analysis of covid-19 in china after wuhan was restricted. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e34 9. zu zy, jiang md, xu pp, chen w, ni qq, lu gm, et al. coronavirus disease 2019 (covid-19): a perspective from china. radiology. 2020:200490. 10. jiang f, deng l, zhang l, cai y, cheung cw, xia z. review of the clinical characteristics of coronavirus disease 2019 (covid-19). journal of general internal medicine. 2020:1-5. 11. zhu n, zhang d, wang w, li x, yang b, song j, et al. a novel coronavirus from patients with pneumonia in china, 2019. new england journal of medicine. 2020. 12. chen h, guo j, wang c, luo f, yu x, zhang w, et al. clinical characteristics and intrauterine vertical transmission potential of covid-19 infection in nine pregnant women: a retrospective review of medical records. the lancet. 2020. 13. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 14. organization. wh. novel coronavirus situation report -2. january 22, 2020. available from: https://w ww.who.int/docs/defaultsource/coronaviruse/situation-reports/20200122sitrep-2-2019-ncov. pdf (accessed on january 23, 2020). 15. wang x, zhou z, zhang j, zhu f, tang y, shen x. a case of 2019 novel coronavirus in a pregnant woman with preterm delivery. clinical infectious diseases: an official publication of the infectious diseases society of america. 2020. 16. liu w, wang q, zhang q, chen l, chen j, zhang b, et al. coronavirus disease 2019 (covid-19) during pregnancy: a case series. 2020. 17. liu d, li l, wu x, zheng d, wang j, liang b, et al. pregnancy and perinatal outcomes of women with covid19 pneumonia: a preliminary analysis. available at ssrn 3548758. 2020. 18. chua msq, lee jcs, sulaiman s, tan hk. from the frontlines of covid-19–how prepared are we as obstetricians: a commentary. bjog: an international journal of obstetrics & gynaecology. 2020. 19. lu q, shi y. coronavirus disease (covid-19) and neonate: what neonatologist need to know. journal of medical virology. 2020. 20. liang h, acharya g. novel corona virus disease (covidâăř19) in pregnancy: what clinical recommendations to follow? acta obstetricia et gynecologica scandinavica. 2020. 21. favre g, pomar l, musso d, baud d. 2019-ncov epidemic: what about pregnancies? the lancet. 2020;395(10224):e40. 22. da s, al. g. potential maternal and infant outcomes from (wuhan) coronavirus 2019-ncov infecting pregnant women: lessons from sars, mers, and other human coronavirus infections. viruses. 2020;12(2):1-16. 23. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. 2020. 24. zhu h, wang l, fang c, peng s, zhang l, chang g. clinical analysis of 10 neonates born to mothers with 2019ncov pneumonia. transl pediatr. 2020;9(1):51-60. 25. lam cm, wong sf, leung tn, chow km, yu wc, wong ty, et al. a case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. bjog: an international journal of obstetrics & gynaecology. 2004;111(8):771-4. 26. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. 27. li q, guan x, wu p, wang x, zhou l, tong y, et al. early transmission dynamics in wuhan, china, of novel coronavirusâăşinfected pneumonia. new england journal of medicine. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion declarations references archives of academic emergency medicine. 2020; 8(1): e63 le t t e r to ed i to r changes in fracture epidemiology due to covid-19 crisis; a letter to editor seyyed saeed khabiri1∗, mohammad hossein nabian2, heydar zeynolabedin3, javad veisi3, vahid rastgou3, mehdi naderi4, shokofeh maleki4 1. department of orthopedic surgery, clinical research development centre, taleghani and imam ali hospitals, kermanshah university of medical sciences, kermanshah, iran. 2. department of orthopedic surgery, joint reconstruction research center, tehran university of medical sciences, tehran, iran. 3. department of orthopedic surgery, faculty of medicine, kermanshah university of medical science, kermanshah, iran. 4. clinical research development centre, taleghani and imam ali hospitals, kermanshah university of medical sciences, kermanshah, iran. received: april 2020; accepted: april 2020; published online: 21 april 2020 cite this article as: khabiri s s, nabian m h, zeynolabedin h, veisi j, rastgou v, naderi m, maleki sh. changes in fracture epidemiology due to covid-19 crisis; a letter to editor. arch acad emerg med. 2020; 8(1): e63. dear editor since december 2019, when the first case of covid-19 was reported in china, the main strategy of health policy makers has been to quarantine and impose social restrictions, causing significant behavioral changes in people due to fear of infection (1, 2). laws limiting traffic, reduced travel permits, paying attention to personal hygiene, and making efforts to clean up private and public environments are some of the changes that have been observed. we also noticed alterations in patients’ admission to trauma centers. in a retrospective cross-sectional study, demographic characteristics and type of fracture were analyzed in patients referring to the trauma center of taleghani hospital, kermanshah, iran, from 1s t march to 15t h april, in 3 consecutive years (2018 to 2020). 2,483 trauma patients with the mean age of 37.31 ± 22.86 years were studied (table1). the findings showed that, the number of fractures has generally decreased in march and april 2020. the change is more prominent in children and young men aged 18 to 35 years, which may be due to reasons such as schools being closed, sports activities being ceased, and the decrease in traffic, as well as the reduction of accidents that have affected these age groups. the age, gender, and type of fracture had approximately the same pattern during the studied period in three years, but we have seen an increase in some specific fractures such as foot bone and ankle (figure1). the fractures of middle-aged women, such as those ∗corresponding author: seyyed saeed khabiri; department of orthopedic surgery, taleghani hospital, faculty of medicine, kermanshah university of medical science, kermanshah, iran. p.o box: 6715847167. e-mail: saeed.khabiri@gmail.com, tel: +98-83-38367984 with osteoporosis, like proximal femur, humerus, and distal radius, seem to have decreased in number during this period. in the study of scott et al., during quarantine and social distancing, despite the decrease in the total number of patients, fragility fracture statistics had remained the same (3). also, in the study of chui et al., they noted that due to cancellation of elective surgeries and the reduction of hospital workload, patients with pelvic fractures will be able to receive preoperative care faster. and better care has been provided for these patients during the covid-19 era (4). indoor layout optimization and strengthening the muscles to prevent falling and care for high-risk people is important. a program to treat osteoporosis should also be actively implemented in people over the age of 65. it could be concluded that during the corona era, because of the behavioral change of the people and the decrease in traffic, we have witnessed a decline in hospital referrals due to trauma and also a decrease in the incidence of fractures, especially those related to accidents. this report may help guide the efforts to improve the healthcare system for crisis preparedness and assist in allocating resources for treatment and predicting workloads. 1. declarations 1.1. acknowledgment the authors would like to thank amir akhashi, nader bahrami, salam ghamari, omid sohrabi, bahareh safari, and clinical research development centers of taleghani and imam ali hospitals, kermanshah university of medical sciences, kermanshah, iran, for support, data gathering, cooperation and assistance throughout the study period. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s s. khabiri et al. 2 figure 1: types and number of fractures during the covid-19 outbreak (march and april of 2020) and similar periods in 2018 and 2019. table 1: number of cases referred to the emergency department with fractures based on gender and age in the studied years characteristic march 1s t to april 15t h 2018 2019 2020 fracture number 957 948 578 gender male 605 (63.2) 602 (63.5) 393 (67.9) female 352 (36.8) 346 (36.5) 185 (32.1) age mean ± sd 35.41±22.65 37.97±23.15 39.37±22.51 sd: standard deviation. 1.2. authors contributions conception and design of the study: mohammad hossein nabian and seyyed saeed khabiri collection, assembly, possession of raw data: heydar zeynolabedin, javad veisi, vahid rastgou and seyyed saeed khabiri statistical expertise :mehdi naderi and shokofeh maleki analysis and interpretation of data: seyyed saeed khabiri and mehdi naderi authors orcids seyyed saeed khabiri: 0000-0002-8906-7660 1.3. funding no benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e63 1.4. conflict of interest the authors declare that there is no conflict of interest. references 1. parmet we, sinha ms. covid-19–the law and limits of quarantine. new england journal of medicine. 2020;382(15):e28. 2. wozniak a. disparities and mitigation behavior during covid-19. federal reserve bank of minneapolis; 2020. 3. scott ce, holland g, powell-bowns mf, brennan cm, gillespie m, mackenzie sp, et al. population mobility and adult orthopaedic trauma services during the covid-19 pandemic: fragility fracture provision remains a priority. bone & joint open. 2020;1(6):182-9. 4. chui k, thakrar a, shankar s. evaluating the efficacy of a two-site (covid-19 and covid-19-free) trauma and orthopaedic service for the management of hip fractures during the covid-19 pandemic in the uk. bone & joint open. 2020;1(6):190-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2020; 8(1): e40 co m m e n ta ry metronidazole; a potential novel addition to the covid19 treatment regimen reza gharebaghi1,2, fatemeh heidary2,3∗, mohammad moradi2,4, maryam parvizi2,5 1. kish international campus, university of tehran, tehran, iran. 2. international virtual ophthalmic research center (ivorc). 3. taleghani hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 4. department of surgery, iran university of medical sciences, tehran, iran. 5. department of pathology, mofid children’s hospital, shahid beheshti university of medical sciences, tehran, iran. received: march 2020; accepted: march 2020; published online: 30 march 2020 abstract: coronavirus disease 2019 or covid-19 has rapidly emerged as a global pandemic. this viral infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death. certain studies have found higher initial plasma levels of most pro-inflammatory cytokines during the course of the infection. in this context, both in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines, which are known to increase during the covid-19 infection, including interleukin (il)8, il6, il1b, tumor necrosis factor (tnf)α, il12, il1α, and interferon (ifn)γ, as well as the levels of c-reactive protein (crp) and neutrophil count. furthermore, the drug could decrease neutrophil-generated reactive oxygen species during inflammation. metronidazole could counteract majority of the immunopathological manifestations of the covid-19 infection. therefore, studies with a large sample size are required to determine the efficacy of metronidazole in the treatment of covid-19 infection. keywords: coronavirus disease; covid-19; metronidazole; cytokines; interleukins cite this article as: gharebaghi r, heidary f, moradi m, parvizi m. metronidazole; a potential novel addition to the covid-19 treatment regimen. arch acad emerg med. 2020; 8(1): e40. 1. introduction coronavirus disease 2019 or covid-19 has rapidly emerged as a global pandemic since its first report in december 2019 in china (1, 2). the infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death (3). currently, no specific treatment is available, and most strategies are principally symptomatic. therefore, finding an effective and economical treatment strategy is essential, particularly for those with lifethreatening infection (4). here, we present evidence from the literature of immunological manifestations of the covid-19 infection and the potential effect of metronidazole in counteracting majority of these immunopathological features. ∗corresponding author: fatemeh heidary; head of ophthalmology division, taleghani hospital, padad, ahvaz jundishapur university of medical sciences, ahvaz, iran. email: drfatemehheidari@yahoo.com office: +98-21-47627292 2. immunopathological evidence of covid-19 following an evaluation of 41 admitted patients with laboratory-confirmed covid-19 infection in wuhan, china, huang et al. found higher initial plasma levels of most proinflammatory cytokines, including interleukin (il)1b, il1ra, il7, il8, il9, il10, basic fibroblast growth factor (fgf), granulocyte-colony stimulating factor (gcsf), granulocytemacrophage colony-stimulating factor (gmcsf), interferon (ifn)γ, ifn-γ inducible protein 10 (ip10), monocyte chemoattractant protein 1 (mcp1), macrophage inflammatory protein (mip)1a, mip1b, platelet-derived growth factor (pdgf), tumor necrosis factor (tnf)α, and vascular endothelial growth factor (vegf) in both intensive care unit (icu) and non-icu patients than in the healthy subjects. however, the plasma levels of il5, il12p70, il15, eotaxin, and rantes were similar. further evaluation revealed higher plasma levels of il2, il7, il10, gcsf, ip10, mcp1, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. gharebaghi et al. 2 mip1a, and tnfα in icu-admitted patients than in non-icu patients (5). chen et al., who retrospectively evaluated 99 patients with laboratory-confirmed covid-19 infection, reported lymphopenia in 35% of cases, as well as increased levels of neutrophils, il6, erythrocyte sedimentation rate (esr), and creactive protein (crp) in 35%, 52%, 85%, and 86% of cases, respectively (6). however, whether the virus directly infects the immune cells, including neutrophils and lymphocytes, is yet to be established (7). zhou et al. conducted a retrospective multicenter study of 191 patients with laboratoryconfirmed covid-19 infection and reported elevated il6 levels and severe lymphopenia in non-survivors than in the survivors. univariate analysis of the data revealed significant associations of lymphopenia and elevated il6 serum levels with mortality (8). 3. immunopharmacology of metronidazole metronidazole [1-(2-hydroxyethyl)-2-methyl-5nitroimidazole] and related 5-nitroimidazoles are redox-active prodrugs that act as biocidal agents via their interaction with a nitroreductase homolog (9). both in vitro and in vivo studies have revealed that metronidazole decreases the levels of several cytokines, including il8 (10-13), il6 (10-15), il1b (1015), tnfα (11-13, 15-17), il12 (11, 13, 14), and ifnγ (11, 14, 16), as well as the levels of crp (11, 12) and neutrophil count (11, 17, 18). interestingly, these parameters are shown to increase during the covid-19 infection (5-7). moreover, metronidazole could increase the number of circulatory lymphocytes (11, 17) and has lymphoproliferative properties, suggestive of its immunopotentiating effect (11, 19). these immunomodulatory effects of metronidazole have been discussed in detail in a previously published review by shakir et al. (11). furthermore, this medication could decrease neutrophil-generated reactive oxygen species during inflammation (11, 20). table 1 summarizes the effects of metronidazole on the immunopathological manifestations of the covid-19 infection. metronidazole, owing to its immunopharmacological behavior, plays a pivotal role in several essential biological processes. based on the reported immunological manifestations of covid-19 infection, it could serve as a potential candidate to counteract majority of the immunopathological features of the disease. therefore, clinical trials with a large sample size are necessary to determine its efficacy in the treatment of covid-19 infection. table 1: effects of metronidazole on immunopathological manifestations of covid-19 infection covid-19 metronidazole ↑ il8 (5) ↓ il8 (10-13) ↑ il6 (6, 8) ↓ il6 (10-15) ↑ il1b (5) ↓ il1b (10-15) ↑ tnfα (5) ↓ tnfα (11-13, 15-17) ↑ crp (6) ↓ crp (11, 12) ↑ il12 (21) ↓ il12 (11, 13, 14) ↑ ifnγ (5) ↓ ifnγ (11, 14, 16) ↑ neutrophils (5, 6) ↓ neutrophils (11, 17, 18) ↓ lymphocytes (5, 6, 8) ↑ lymphocytes (11, 17), lymphoproliferative properties (11, 19) crp: c-reactive protein; ifn: interferon; il: interleukin; tnf: tumor necrosis factor. 4. declarations 4.1. acknowledgements authors wish to thank the international virtual ophthalmic research center (ivorc) for the continuous academic support. 4.2. authors contributions rg, fh conceived the original idea. rg, fh, mm, and mp designed the scenarios relevant to the idea and collected the relevant manuscripts. they have performed acquisition, analysis, and interpretation of data. rg, fh, mm, mp carried out the evaluation on current evidences on the subject, approved the final version that was submitted, revised it, and drafted the manuscript. all authors are agree to be accountable for all aspects of the work. rg, fh, mm, and mp met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids reza gharebaghi: 0000-0002-4906-8597 fatemeh heidary: 0000-0002-6558-6132 mohammad moradi: 0000-0003-1560-7641 maryam parvizi: 0000-0003-2198-3520 4.3. funding support this research resulted from an independent research without financial support. 4.4. conflict of interest the authors have declared that no competing interests exist. references 1. zhou p, yang xl, wang xg, hu b, zhang l, zhang w, et al. a pneumonia outbreak associated with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e40 a new coronavirus of probable bat origin. nature. 2020;579(7798):270-3. 2. reviglio ve, osaba m, reviglio v, chiaradiap, kuo ic, o’brien tp. covid-19 and ophthalmology: a new chapter in an old story. med hypothesis discov innov ophthalmol. 2020 summer; 9(2): 71-73. 3. bai y, yao l, wei t, tian f, jin d-y, chen l, et al. presumed asymptomatic carrier transmission of covid-19. jama. 2020. 4. wu d, yang xo. th17 responses in cytokine storm of covid-19: an emerging target of jak2 inhibitor fedratinib. journal of microbiology, immunology and infection. 2020. 5. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 6. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. 7. prompetchara e, ketloy c, palaga t. immune responses in covid-19 and potential vaccines: lessons learned from sars and mers epidemic. asian pac j allergy immunol. 2020. 8. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet. 2020. 9. sisson g, jeong j-y, goodwin a, bryden l, rossler n, lim-morrison s, et al. metronidazole activation is mutagenic and causes dna fragmentation in helicobacter pylori and inescherichia coli containing a cloned h. pylori rdxa+(nitroreductase) gene. journal of bacteriology. 2000;182(18):5091-6. 10. yudin mh, landers dv, meyn l, hillier sl. clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial. obstetrics & gynecology. 2003;102(3):527-34. 11. shakir l, javeed a, ashraf m, riaz a. metronidazole and the immune system. die pharmazie-an international journal of pharmaceutical sciences. 2011;66(6):393-8. 12. bayraktar mr, mehmet n, durmaz r. serum cytokine changes in turkish children infected with giardia lamblia with and without allergy: effect of metronidazole treatment. acta tropica. 2005;95(2):116-22. 13. rizzo a, paolillo r, guida l, annunziata m, bevilacqua n, tufano ma. effect of metronidazole and modulation of cytokine production on human periodontal ligament cells. international immunopharmacology. 2010;10(7):744-50. 14. fitzpatrick lr, small j, hoerr ra, bostwick ef, maines l, koltun wa. in vitro and in vivo effects of the probiotic escherichia coli strain m-17: immunomodulation and attenuation of murine colitis. british journal of nutrition. 2008;100(3):530-41. 15. amar s, wu s-c, madan m. is porphyromonas gingivalis cell invasion required for atherogenesis? pharmacotherapeutic implications. the journal of immunology. 2009;182(3):1584-92. 16. mercer-jones m, hadjiminas d, heinzelmann m, peyton j, cook m, cheadle w. continuous antibiotic treatment for experimental abdominal sepsis: effects on organ inflammatory cytokine expression and neutrophil sequestration. british journal of surgery. 1998;85(3):385-9. 17. fararjeh m, mohammad mk, bustanji y, alkhatib h, abdalla s. evaluation of immunosuppression induced by metronidazole in balb/c mice and human peripheral blood lymphocytes. international immunopharmacology. 2008;8(2):341-50. 18. lefebvre y, hesseltine hc. the peripheral white blood cells and metronidazole. jama. 1965;194(1):15-8. 19. elizondo g, montero r, herrera je, hong e, ostroskywegman p. lymphocyte proliferation kinetics and sisterchromatid exchanges in individuals treated with metronidazole. mutation research/fundamental and molecular mechanisms of mutagenesis. 1994;305(2):133-7. 20. akamatsu h, oguchi m, nishijima s, asada y, takahashi m, ushijima t, et al. the inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne. archives of dermatological research. 1990;282(7):449-54. 21. li x, geng m, peng y, meng l, lu s. molecular immune pathogenesis and diagnosis of covid-19. journal of pharmaceutical analysis. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction immunopathological evidence of covid-19 immunopharmacology of metronidazole declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 109 emergency (2015); 3 (3): 109-113 original research comparison of oral midazolam and promethazine with oral midazolam alone for sedating children during computed tomography hassan barzegari, behzad zohrevandi, kambiz masoumi, arash forouzan*, ali asgari darian, shaqayeq khosravi department of emergency medicine, ahvaz jundishapur university of medical sciences, ahvaz, iran. *corresponding author: arash forouzan; department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, azadegan avenue, ahvaz, khuzestan province, iran. postal code: 6193673166; tel/fax: +986112229166; email: md_89864@yahoo.com received: january 2015; accepted: march 2015 abstract introduction: both midazolam and promethazine are recommended to be used as sedatives in many studies but each have some side effects that limits their use. combination therapy as an alternative method, may decreases these limitations. therefore, this study aimed to compare midazolam with midazolam-promethazine regarding induction, maintenance, and recovery characteristics following pediatric procedural sedation and analgesia . methods: children under 7 years old who needed sedation for being ct scanned were included in this double-blind randomized clinical trial. the patients were randomly divided into 2 groups: one only received midazolam (0.5 mg/kg), while the other group received a combination of midazolam (0.5 mg/kg) and promethazine (1.25 mg/kg). university of michigan sedation scale (umss) was used to assess sedation induction. in addition to demographic data, the child’s vital signs were evaluated before prescribing the drugs and after inducing sedation (reaching umss level 2). the primary outcomes in the present study were onset of action after administration and duration of the drugs’ effect. results: 107 patients were included in the study. mean onset of action was 55.4±20.3 minutes for midazolam and 32.5±11.1 minutes for midazolam-promethazine combination (p<0.001). but duration of effect was not different between the 2 groups (p=0.36). 8 (7.5%) patients were unresponsive to the medication, all 8 of which were in the midazolam treated group (p=0.006). also in 18 (16.8%) cases a rescue dose was prescribed, 14 (25.9%) were in the midazolam group and 4 (7.5%) were in the midazolam-promethazine group (p=0.02). comparing systolic (p=0.20) and diastolic (p=0.34) blood pressure, heart rate (p=0.16), respiratory rate (p=0.17) and arterial oxygen saturation level (p=0.91) showed no significant difference between the 2 groups after intervention. conclusion: based on the findings of this study, it seems that using a combination of midazolam and promethazine not only speeds up the sedation induction, but also decreases unresponsiveness to the treatment and the need for a rescue dose. key words: promethazine; midazolam; anti-anxiety agents; conscious sedation cite this article as: barzegari h, zohrevandi b, masoumi k, forouzan a, asgari darian a, khosravi sh. comparison of oral midazolam and promethazine with oral midazolam alone for sedating children during computed tomography. emergency. 2015;3(3):109-13 introduction: rocedural sedation and analgesia are constantly used procedures range from pain-free interventions such as imaging, to painful intervention like fracture reduction, wounds care, bone marrow aspiration, and placing a central venous catheter (1, 2). sedating the patients, allows them to bear these unpleasant procedures while their cardiorespiratory function remains constant. these measures lead to increased quality of care, patients’ satisfaction, reduced pain and anxiety, and earlier diagnosis and treatment (3-8). pediatric imaging is one of the most indication of procedural sedation and analgesia. in the pediatric patient, performing ct scan is stressful and leads to increased mental stress, absence of cooperation with the staff, restlessness, and anxiety in the patient. these reactions not only interfere with the treatments but also lead to changes in physiologic parameters such as blood pressure, heart rate, resp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com barzegari et al 110 piratory rate, and etc. (9, 10). selecting the precise medication is very important in these situations. using a suitable sedative, results in a decrease in the rescue dose and increases the safety of the procedure (11). most of these medications can be prescribed through various routes and selecting the best drug varies based on the procedure, level of pain, optimum depth of sedation, and the patient’s condition (1, 12, 13). although there are lots of drugs that induce conscious sedation, but their side effects have limited their clinical use (14, 15). some studies have suggested using combination therapy as they show increased effectiveness, decreased loading dose, and therefore decreased side effects (8, 9, 16, 17). midazolam has been used as a sedative in children for a long time. this short-acting benzodiazepine acts as a sedative, amnesic and stress reliever. it is preferred to long-acting benzodiazepines such as diazepam (18, 19). but using oral midazolam alone, shows a high rate of failure in sedation (20, 21). promethazine is another agent that is used for sedating children (22, 23). it is a common antiemetic that has been used as a safe and effective drug with a low rate of side effects and failure. therefore using it combined with midazolam, may decreases midazolam’s limitations, but to date no study has been done to compare the sedative effect of midazolam alone with midazolam-promethazine, in children undergoing ct scan. for these reasons, this study aimed to compare midazolam with midazolam-promethazine regarding induction, maintenance, and recovery characteristics following pediatric procedural sedation and analgesia. methods: study design: this double-blind randomized clinical trial was done in a medical center in ahwaz, iran in 2013. protocol of the study was approved by the ethics committee of jondishapour university of medical sciences, ahwaz, iran. the researchers abided by the principles of helsinki declaration in the evaluations and prescribing the medications. signed consent forms were obtained from patients’ parents. patients: healthy children under 7 years old who needed sedation for undergoing ct scan were included based on american society of anesthesiologists (asa i and ii) scale. exclusion criteria included allergy to midazolam or promethazine, gastritis, any serious systemic disease, severe systemic reaction, severe cardiovascular disease, coronary artery disease, head trauma, eye trauma, central nervous system disease, contraindications to sedation, receiving sedative-hypnotic drugs in the last 48 hours. sampling was consecutive. the sample size was determined as 51 patients in each group, considering standard deviation range of 3 to 23 minutes for midazolam’s duration of effect (4, 5, 24), with α=0.05 and β=0.1 and maximum error of 1.5 minutes (d=1.5). intervention: patients were enrolled consecutively and randomly divided into 2 groups: one only received midazolam (a dose of 0.5 mg/kg weight), while the other group received midazolam (a dose of 0.5 mg/kg weight) plus promethazine (a dose of 1.25 mg/kg weight). block randomization was executed using a computer software. the drugs were obtained from rotexmedica company (germany). to ensure that the patients remained unaware of the treatment assignment, an hour before ct scan, oral promethazine was prescribed for the combination group while the other group drank a sugar syrup. 20 minutes before the ct scan, both groups received midazolam. all the drugs were mixed with fruit juice. in case of vomiting in the initial 15 minutes after receiving midazolam, this drug would be prescribed again with the same dose. the data were gathered by another researcher for ensuring blindness to therapy. the drugs were administrated when the level of arterial saturated oxygen was above 95% and in case of any drop in the oxygen saturation, oxygen therapy would be started. if the patient didn’t respond to treatment, a rescue dose (50% of the initial midazolam dose) would be used. variables: level of sedation was assessed every 10 minutes since receiving midazolam based on university of michigan sedation scale (umss). this scale has 5 levels which is shown in panel 1. in addition to demographic data (age, sex, weight), the child’s vital signs (respiratory rate, heart rate and level of arterial saturated oxygen) were evaluated before prescribing the drugs and after inducpanel 1: university of michigan sedation scale score definition 0 awake/alert. 1 minimally sedated: tired/sleepy, appropriate response to verbal conversation and/or sounds. 2 moderately sedated: somnolent/sleeping, easily aroused with light tactile stimulation. 3 deeply sedated: deep sleep, arousable only with significant physical stimulation. 4 unarousable this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 111 emergency (2015); 3 (3): 109-113 ing sedation (reaching umss level 2). finally, any side effect related to the prescribed drugs would be recorded. outcomes: the primary outcomes in the present study were onset of action after administration and duration of the drugs’ effect. to evaluate the onset of action, the time interval between midazolam prescription and sedation induction (reaching umss level 2) was calculated. for evaluating the duration of effect, the time interval between sedation induction and complete awareness (reaching umss level 0) was recorded. secondary outcomes included incidence of the drugs’ side effects, heart rate, blood pressure, respiratory rate, arterial oxygen saturation level, needing a rescue dose and no response to the treatment (not reaching umss level 2). statistical analysis: the data were entered in spss 21.0. quantitative data were expressed as mean ± standard deviation and qualitative data were shown as frequency and percentage. to compare the 2 groups regarding demographic and clinical factors before intervention chi square test (for nominal qualitative variables) and mann-whitney u test (for quantitative and ordinal variables) were used. also, the 2 groups were compared regarding onset and duration of effect, using mann-whitney u test. since the children’s vital signs before intervention was significantly different in the 2 groups, non-parametric analysis of covariance was used to compare these factors in the groups. in all the analyses p<0.05 was considered the significance level. results: 107 children were included in the study (54 patients in the midazolam group and 53 in the midazolam-promethazine group). mean age was 36.0±15.5 months in the midazolam group and 36.8±13.7 months in the midazolam-promethazine group (p=0.79). 31 (57.4%) patients in the midazolam group and 28 (52.8%) in the midazolam-promethazine group were male (p=0.63). table 1 shows the distribution of demographic and clinical factors before intervention. as can be seen, only respiratory rate was significantly different in the groups (p=0.01). mean onset of action for midazolam (55.4±20.3 minutes) was significantly more than midazolam-promethazine combination (32.5±11.1 minutes) (p<0.001). but duration of effect was not different between the 2 groups (p=0.36) (figure 1). 8 (7.5%) patients were unresponsive to the medication, all 8 of which were in the midazolam table 1: comparing demographic and clinical factors of the patients before intervention variable midazolam midazolam+ promethazine p age (month) 36.0 (15.5) 36.8 (13.7) 0.79 weight (kg) 14.7 (3.3) 14.2 (2.6) 0.46 sbp (mm hg) 97.1 (8.1) 98.9 (5.5) 0.17 dbp (mm hg) 59.1 (5.5) 60.6 (3.5) 0.09 heart rate (per min) 115.1 (11.1) 112.9 (10.3) 0.29 respiratory rate (per min) 19.9 (2.7) 18.8 (2.0) 0.01 oxygen saturation (%) 98.6 (0.7) 98.7 (0.6) 0.6 a b figure 1: onset of action (a) and duration of effect (b) of midazolam and midazolam-promethazine in sedation of the children. *, shows significant difference at p<0.001. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com barzegari et al 112 treated group (p=0.006). also in 18 (16.8%) cases a rescue dose was prescribed, 14 (25.9%) were in the midazolam group and 4 (7.5%) were in the midazolam-promethazine group (p=0.02). only 2 cases of nausea and vomiting was seen both of which were in the midazolam group (p=0.99). comparing systolic (p=0.20) and diastolic (p=0.34) blood pressure, heart rate (p=0.16), respiratory rate (p=0.17) and arterial oxygen saturation level (p=0.91) showed no significant difference between the 2 groups after intervention (table 2). discussion: the findings of this study showed that mean onset of action for midazolam is significantly longer compared to midazolam-promethazine combination, while their duration of effect is no different. in addition, the frequency of not responding to treatment and needing a rescue dose is higher in the midazolam treated group. yet, both treatments have similar effects on nausea and vomiting, blood pressure, heart rate, respiratory rate and arterial oxygen saturation level. therefore, it seems that using a combination of midazolam and promethazine not only speeds up the sedation induction, but also decreases unresponsiveness to the treatment and the need for a rescue dose. in line with this study, cengiz et al. showed that the onset of action in a combination of midazolam and diphenhydramine is shorter than midazolam alone, while their duration of effect in no different (25). also, jain et al. expressed the same results regarding onset of action comparing midazolam-ketamine combination with midazolam (26). in addition, parkinson et al. (27) and crean (28) demonstrated in their respective studies that promethazine combined with chloral hydrate has a better sedative effect on children compared to midazolam alone. houpt et al. showed that using chloral hydrate (dose: 25 mg/kg) combined with promethazine, is no different to using a 50 mg/kg chloral hydrate regarding sedation level and hemodynamic factors (29). in the present study, 2 cases of nausea were seen in the midazolam group despite this drug having an antiemetic properties, which might be due to its bitter taste. in the combination group no nausea and vomiting was seen. since promethazine had been received earlier in this group, the anti-histaminic and anti-cholinergic effects of promethazine might have controlled the nausea (22). the combination treatment using midazolam plus promethazine in children under 7 years old lead to a significant decrease in midazolam’s failure and improved its effectiveness as expected. midazolam is a short-acting benzodiazepine that exerts its effect by affecting gaba receptors and resulting in chloride ion influx to the neuron (25), while promethazine acts on histamine and cholinergic receptors of medullary reticular formation to show its sedative effects (23). based on the findings of this study we can conclude that promethazine amplifies the effects of midazolam by affecting medulla and pons and leads to a decrease in its failure rate. little sample size and short follow-up time are of the limitations of this study. therefore it is recommended to increase sample size and follow-up time in future studies. conclusion: the findings of this study showed that mean onset of action for midazolam is significantly longer compared to midazolam-promethazine combination, while their duration of effect is no different. in addition, the frequency of not responding to treatment and needing a rescue dose is higher in the midazolam treated group. yet, both treatments have similar effects on nausea and vomiting, blood pressure, heart rate, respiratory rate and arterial oxygen saturation level. therefore, it seems that using a combination of midazolam and promethazine not only speeds up the sedation induction, but also decreases unresponsiveness to the treatment and the need for a rescue dose. acknowledgments: this work is a part of the academic thesis of dr. shaqayeq khosravi’s (no.eth-371) in ahvaz jundishapur university of medical sciences. the authors would like to thank ms. mehrnoosh yazdanbakhsh for her invaluable helps. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. barkan s, breitbart r, brenner-zada g, et al. a double-blind, randomised, placebo-controlled trial of oral midazolam plus table 2: comparing clinical factors of the patients after intervention variable midazolam midazolam+ promethazine p* sbp (mm hg) 93.2 (7.5) 94.8 (4.7) 0.20 dbp (mm hg) 60.4 (6.7) 63.0 (5.4) 0.34# heart rate (per min) 111.5 (10.5) 108.6 (10.8) 0.16 respiratory rate (per min) 18.9 (2.4) 17.6 (1.7) 0.17# oxygen saturation (%) 98.9 (0.8) 98.9 (0.7) 0.91 *, based on mann-whitney u test; #, based on non-parametric analysis of covariance adjusted for pretreatment values. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 113 emergency (2015); 3 (3): 109-113 oral ketamine for sedation of children during laceration repair. emergency medicine journal. 2013:emermed-2012-202189. 2. azizkhani r, kanani s, sharifi a, golshahi k, masoumi b, ahmadi o. oral chloral hydrate compare with rectal thiopental in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;2(2):85-9. 3. alimohammadi h, shojaee m, samiei m, abyari s, vafaee a, mirkheshti a. nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial. emergency. 2013;1(1):11-4. 4. azizkhani r, esmailian m, golshani k. rectal thiopental versus intramuscular ketamine in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;3(1):22-6. 5. azizkhani r, kanani s, sharifi a, golshani k, masoumi b, ahmadi o. oral chloral hydrate compare with rectal thiopental in pediatric procedural sedation and analgesia; a randomized clinical trial. emergency. 2014;2(2):85-9. 6. khajavi m, emami a, etezadi f, safari s, sharifi a, moharari rs. conscious sedation and analgesia in colonoscopy: ketamine/propofol combination has superior patient satisfaction versus fentanyl/propofol. anesthesiology and pain medicine. 2013;3(1):208-12. 7. alimohammadi h, azizi m-r, safari s, amini a, kariman h, hatamabadi hr. axillary nerve block in comparison with intravenous midazolam/fentanyl for painless reduction of upper extremity fractures. acta medica iranica. 2014;52(2):122-4. 8. hosseini m, karami z, janzadenh a, et al. the effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. emergency. 2014;2(4):pp. 1517. 9. moreira ta, costa ps, costa lr, et al. combined oral midazolam–ketamine better than midazolam alone for sedation of young children: a randomized controlled trial. international journal of paediatric dentistry. 2013;23(3):20715. 10. maurizi p, russo i, rizzo d, et al. safe lumbar puncture under analgo-sedation in children with acute lymphoblastic leukemia. international journal of clinical oncology. 2014;19(1):173-7. 11. krauss bs, krauss ba, green sm. procedural sedation and analgesia in children. new england journal of medicine. 2014;370(15):e23. 12. krauss b, green sm. procedural sedation and analgesia in children. the lancet. 2006;367(9512):766-80. 13. lee jh, kim k, kim ty, et al. a randomized comparison of nitrous oxide versus intravenous ketamine for laceration repair in children. pediatric emergency care. 2012;28(12):1297-301 10.097/pec.0b013e3182768a86. 14. song jh. procedural sedation and analgesia in children. journal of the korean medical association. 2013;56(4):271-8. 15. messeri a, astuto m. procedural sedation and analgesia in children. pediatric anesthesia, intensive care and pain: standardization in clinical practice: springer; 2013. p. 47-59. 16. nasirinezhad f, sagen j. nmda antagonist peptide supplementation enhances pain alleviation by adrenal medullary transplants. cell transplantation. 2005;14(4):20311. 17. vannatta me, rex dk. propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy. the american journal of gastroenterology. 2006;101(10):2209-17. 18. bayardo ra, herrera ml, aceves l. midazolam conscious sedation in 2-4 years old children. rgo. 2012;60(3):367-70. 19. ghajari mf, golpayegani mv, bargrizan m, ansari g, shayeghi s. sedative effect of oral midazolam/hydroxyzine versus chloral hydrate/hydroxyzine on 2–6 year-old uncooperative dental patients: a randomized clinical trial. journal of dentistry (tehran, iran). 2014;11(1):93-8. 20. fallah r, nakhaei mha, behdad s, moghaddam rn, shamszadeh a. oral chloral hydrate vs. intranasal midazolam for sedation during computerized tomography. indian pediatrics. 2013;50(2):233-5. 21. d’agostino j, terndrup te. chloral hydrate versus midazolam for sedation of children for neuroimaging: a randomized clinical trial. pediatric emergency care. 2000;16(1):1-4. 22. cook ba, bass jw, nomizu s, alexander me. sedation of children for technical procedures current standard of practice. clinical pediatrics. 1992;31(3):137-42. 23. fallah r, jalili s, golestan m, karbasi sa, jarahzadeh m-h. efficacy of chloral hydrate and promethazine for sedation during electroencephalography in children; a randomised clinical trial. iranian journal of pediatrics. 2013;23(1):27-31. 24. fallah r, fadavi n, behdad s, tafti mf. efficacy of chloral hydrate-hydroxyzine and chloral hydrate-midazolam in pediatric magnetic resonance imaging sedation. iranian journal of child neurology. 2014;8(2):11-7. 25. cengiz m, baysal z, ganidagli s. oral sedation with midazolam and diphenhydramine compared with midazolam alone in children undergoing magnetic resonance imaging. pediatric anesthesia. 2006;16(6):621-6. 26. jain k, ghai b, saxena ak, saini d, khandelwal n. efficacy of two oral premedicants: midazolam or a low-dose combination of midazolam–ketamine for reducing stress during intravenous cannulation in children undergoing ct imaging. pediatric anesthesia. 2010;20(4):330-7. 27. parkinson l, hughes j, gill a, billingham i, ratcliffe j, choonara i. a randomized controlled trial of sedation in the critically ill. paediatr anaesth. 1997;7(5):405-10. 28. crean p. sedation and neuromuscular blockade in paediatric intensive care; practice in the united kingdom and north america. paediatr anaesth. 2004;14(6):439-42. 29. houpt mi, weiss nj, koenigsberg s, desjardins p. comparison of chloral hydrate with and without promethazine in the sedation of young children. pediatr dent. 1985;7(1):416. emergency. 2018; 6 (1): e24 or i g i n a l re s e a rc h lidocaine-midazolam-fentanyl combination in controlling pain for reduction of anterior shoulder dislocation; a randomized clinical trial ali arhami dolatabadi1, aida mohammadian1∗, hamid kariman1 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: march 2018; accepted: april 2018; published online: 16 april 2018 abstract: introduction: finding a fast-acting compound with minimal side-effects to induce a safe and efficient analgesia with short or medium duration of action is of great interest in the emergency department. the present study has been designed with the aim of comparing the effect of midazolam + fentanyl + lidocaine combination with midazolam + fentanyl + placebo in pain management of anterior shoulder dislocation reduction. methods: the present two-arm parallel double-blind randomized controlled trial was performed on patients who presented to emergency department with anterior shoulder dislocation. patients were randomly allocated to the 2 treatment groups of midazolam + fentanyl + placebo (double-drug group) and midazolam + fentanyl + intravenous (iv ) lidocaine (triple-drug group). then outcomes such as treatment success rate and side-effects following prescription of drugs were compared between the 2 groups. results: 100 patients were included in the present study (50 patients in each group; mean age of the studied patients 27.3±8.9 years; 93.0% male). using the double-drug regimen led to 35 (70%) cases of complete analgesia, while this rate in the triple-drug group was 41 (82%) cases (p=0.16). the calculated number needed to treat was 9 cases. this means that about one in every 9 patients in treatment arm will benefit from the treatment. the most important side-effects observed included dysrhythmia (1 patient in double drug and 1 patient in triple-drug group), apnea (2 patients in each group) and spo2<90% (2 patients in triple-drug group) (p=0.78). number needed to harm was 25 cases. in other words, for each 25 patients treated with the triple drug regimen, 1 case of spo2<90% is observed. conclusion: findings of the present study showed that adding iv lidocaine to iv midazolam + fentanyl drug combination does not provide additional analgesia in sedation for anterior shoulder reduction. keywords: conscious sedation; midazolam; fentanyl; lidocaine; combined modality therapy © copyright (2018) shahid beheshti university of medical sciences cite this article as: arhami dolatabadi a, mohammadian a, kariman h. lidocaine-midazolam-fentanyl combination in controlling pain for reduction of anterior shoulder dislocation; a randomized clinical trial. emergency. 2018; 6(1): e24. 1. introduction o ne of the painful treatment interventions in need of procedural sedation and analgesia (psa) is reduction of anterior shoulder dislocation and the statistics are indicative of its 1 1.7% prevalence in societies. the prevalence of these dislocations is higher among those in the age range of 20 – 30 years and affects men more than women (1). using a proper analgesia method for controlling the pain of these patients during reduction is of great interest (2-4). ∗corresponding author: aida mohammadian, emergency department, imam hossein hospital, imam hossein square, shahid madani avenue, tehran, iran. tel: 00989126053463 email: aidamohammadian@yahoo.com for this purpose, emergency medicine specialists are constantly seeking a fast-acting compound with minimal sideeffects to induce a safe and efficient analgesia with short or medium duration of action in patients. the first suggested protocols of psa were based on single-drug strategies, which had a strong emphasis on using opioids, propofol, midazolam, or fentanyl alone (5). however, for achieving lasting sedation in these single-drug protocols, a high dose of the mentioned drugs were required, which would result in serious side-effects such as depression of the central nervous system (cns), apnea and dangerous hypoxia (6). sometimes, there would be cases that even by using the highest dose allowed, proper sedation would not be induced (7, 8). therefore, to relieve this deficiency, the researchers turned to double-drug strategies so that they could not only reduce the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. arhami dolatabadi et al. 2 dose of consumption for each drug, but also achieve double effectiveness by using drugs that have different mechanisms of action. among these drug combinations are propofol + midazolam, propofol + fentanyl, midazolam + fentanyl, and etc. (9-17). however, these double-drug protocols also have limitations, among which are lack of complete effectiveness and considerable treatment failures in patients (6). therefore, it is possible that adding another drug to these treatment protocols improves the effectiveness and reduces the side-effects. lidocaine is an anesthetic drug, intravenous (iv ) prescription of which can control pains due to cancer, post-surgery pains, and neuropathic pains (18). lidocaine reduces pain in patients by decreasing the sensitivity and activity of neurons that transmit pain in the cns and decreasing post-synaptic receptors of n-methyl-d-aspartate (19-21). although the effectiveness of local prescription of lidocaine (intra-articular) in controlling the pain following shoulder reduction has been confirmed in a meta-analysis (22), its analgesic effects following iv prescription is less known. on the other hand, no study has been done with the aim of assessing the additive or synergic effects of using lidocaine along with midazolam + fentanyl combination, yet. therefore, the present study was designed with the aim of comparing the effect of iv midazolam + fentanyl + lidocaine combination with midazolam + fentanyl + placebo as psa for reduction of anterior shoulder dislocation in emergency department. 2. methods 2.1. study design and setting the present two-arm parallel double-blind randomized controlled trial was performed on patients who presented to the emergency departments of imam hossein, loghmane hakim, and shohadaye tajrish hospitals, tehran, iran, with anterior shoulder dislocation throughout 2016. the study was approved by the ethics committee of shahid beheshti university of medical sciences and patients were included after obtaining informed consent from the patient or their companion. the researchers adhered to the principles indicated in the declaration of helsinki throughout the study. it should be noted that the protocol of the present study was registered on the iranian registry of clinical trials under the number irct2016101730353n1. 2.2. participants patients with anterior shoulder dislocation candidate for reduction were included in the study. patients with altered level of consciousness at the time of presentation, those who had a fracture in their shoulder joint along with shoulder dislocation (apart from lesion sachs-hill), patients with a history of surgery on the same shoulder joint or fracture of the shoulder joint, history of seizure, those who had received analgesic drugs before presenting, patients with history of cardiac diseases and dysrhythmia, history of taking digoxin, and patients with a history of allergy to lidocaine, midazolam, or fentanyl were excluded from the study. 2.3. interventions using a web-based program and via block randomization method (with block size of 5) without stratifying for baseline characteristics, the studied patients were allocated to the 2 treatment groups of iv midazolam + fentanyl + placebo (double-drug group) and iv midazolam + fentanyl + lidocaine (triple-drug group). randomization was performed by a statistics expert who did not participate in the process of sampling and evaluating the outcome of the patients. drugs were prepared as anonymous, colorless, and odorless packs by a senior researcher that played no part in the treatment process and follow-up of the patients and were given to a third year emergency medicine resident who was in charge of prescribing the drugs and evaluating the pain of the patients. before starting therapeutic intervention, baseline characteristics of the patients including age, sex, weight, history of smoking, history of taking opium, history of alcohol consumption, and history of being affected with underlying illnesses would be recorded. then, using visual analog scale (vas), pain of the patients was assessed and recorded. before initiation of sedation, patients underwent hemodynamic evaluation and continuous pulse oximetry and 3 liters of nasal oxygen (their arterial oxygen saturation level would be maintained over 95%). in case of no initial problem, 1 mg/kg lidocaine for patients in the triple-drug group and distilled water (as placebo) in the double-drug group were prescribed intravenously. then both mentioned groups were given midazolam and fentanyl by injection in a titrated manner until the analgesia of the patient reached the score of 4 based on ramsay sedation scale (23). if the patient did not reach the score of 4 despite receiving the maximum allowed dose of the drugs, the case was recorded as a case of failure in sedation and included in the analyses. after the patient reached the score of 4 based on ramsey scale, the midazolam and fentanyl dose used was recorded for each patient and shoulder reduction was performed. after the patient became completely conscious, pain severity was evaluated and recorded based on vas. 2.4. evaluated outcomes the primary outcome evaluated in this study was considered treatment success rate. for this purpose, complete analgesia (vas=0) of the patient after reduction was defined as treatment success. the secondary outcome in the present study was considered the evaluation of side-effects following prescription of drugs including dysrhythmia, apnea, hypoxia, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e24 flowchart 1: flowchart of present study. nausea and vomiting, and other side-effects. in the end, the final dose of fentanyl and midazolam used in the 2 studied groups was evaluated. 2.5. statistical analysis since in the beginning of the present research there was no similar study, a pilot study was performed on 10 patients to determine sample size based on it. mean pain severity of patients after reduction in the pilot study was 1.33 ± 0.82 in the double-drug group and 0.82 ± 0.71 in the triple-drug group. therefore, by considering 90% power (β=0.1) and 95% confidence interval (α=0.05), 49 patients in each group was sufficient for the present study, and in the end, 50 patients were included in each group. data were entered to stata 14.0 statistical software and analyzed. quantitative data were reported as mean and standard deviation and qualitative data were reported as frequency and percentage. to compare quantitative data between the 2 studied groups, independent t-test and for comparing qualitative data, chi square or fisher’s exact test were used. in addition, based on complete analgesia, treatment success was calculated and number needed to treat, number needed to harm, absolute risk reduction and relative risk reduction were calculated based on it. in all analyses p<0.05 was considered as the level of significance. 3. results in the end, data of 100 patients were included in the present study (50 patients in each group; flowchart 1). mean age of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. arhami dolatabadi et al. 4 table 1: baseline characteristics of included patients variable double-drug group (n=50) triple-drug group (n=50) total (n=100) p age (year) 27.7±8.7 27.0±9.2 27.3±8.9 0.71 sex male 48 (96.0) 45 (90.0) 93 (93.0) 0.44* female 2 (4.0) 5 (10.0) 7 (7.0) weight (kg) 75.6±9.7 72.7±10.4 74.2±10.1 0.15 smoking status non-smoker 30 (60.0) 26 (52.0) 56 (56.0) 0.42 smoker 20 (40.0) 24 (48.0) 44 (44.0) opium consumption no 39 (78.0) 38 (76.0) 77 (77.0) 0.81 yes 11 (22.0) 12 (24.0) 44 (23.0) alcohol use no 43 (86.0) 42 (84.0) 85 (85.0) 0.78 yes 7 (14.0) 8 (16.0) 15 (15.0) underlying illness none 45 (90.0) 43 (86.0) 88 (88.0) 0.68* diabetes 1 (2.0) 1 (2.0) 2 (2.0) pulmonary 1 (2.0) 2 (4.0) 3 (6.0) hypertension 1 (2.0) 0 (0.0) 1 (1.0) liver 1 (2.0) 0 (0.0) 1 (1.0) other 1 (2.0) 4 (8.0) 5 (5.0) ramsay sedation scale 4 47 (94.0) 49 (98.0) 96 (96.0) 0.62* 5 3 (6.0) 1 (2.0) 4 (4.0) data were reported as mean ± standard deviation or frequency (%). double-drug protocol: midazolam + fentanyl + placebo; triple-drug protocol: midazolam + fentanyl + lidocaine. table 2: outcome of the studied patients variable double-drug group (n=50) triple-drug group (n=50) p visual analogue scale before treatment 8.3±1.3 8.2±1.2 0.55 after treatment 0.6±0.9 0.4±0.8 0.24 success rate* 35 (70.0) 41 (82.0) 0.16 side effects none 47 (94.0) 45 (90.0) 0.78 dysrhythmia 1 (2.0) 1 (2.0) apnea 2 (4.0) 2 (4.0) spo2 <90% 0 (0.0) 2 (4.0) midazolam dosage (mg/kg) 5.9±2.7 5.9±2.5 0.97 fentanyl dosage (µg/kg) 256.0±115.3 246.0±117.7 0.42 data were reported as mean ± standard deviation or frequency (%). *: success rate was defined as complete analgesia (visual analogue scale=0) double-drug protocol: midazolam + fentanyl + placebo; triple-drug protocol: midazolam + fentanyl + lidocaine. the studied patients was 27.3±8.9 years (93.0% male). the 2 groups were not significantly different regarding age (p=0.71) and sex (p=0.44) distribution, smoking (0.42), drug abuse (p=0.81) and alcohol abuse (p=0.81) (table 1). most of the patients (90% in the group with double-drug protocol and 86% in the group with triple-drug protocol) had no history of underlying illnesses (p=0.68). mean vas score before the initiation of treatment in the groups under treatment with double-drug and triple-drug protocols were 8.3±1.3 and 8.2±1.2, respectively (p=0.52) and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e24 table 3: number needed to treat as well as absolute and relative risk reduction of the triple-drug protocol variable value pain reduction number needed to treat (n) 9 absolute risk reduction 12.0% relative risk reduction 0.15 adverse events number needed to harm (n) 25 absolute risk reduction 4.0% relative risk reduction 0.04 after treatment these measures reached 0.6±0.9 and 0.4±0.8 (p=0.24). using the double-drug regimen led to 35 (70%) cases of complete analgesia, while this rate was 41 (82%) cases in the triple-drug group (p=0.16) (table 2). number needed to treat calculated was 9 cases. this means that about one in every 9 patients in treatment arm will benefit from the treatment (table 3). the most important side-effects observed included dysrhythmia (1 patient in double-drug treatment and 1 patient in triple-drug treatment), apnea (2 patients in each group) and spo2<90% (2 patients in triple-drug group) (p=0.78) (table 2). number needed to harm was 25 cases. in other words, for every 25 patients treated with the triple-drug regimen, 1 case of spo2<90% is observed (table 3). 4. discussion findings of the present study showed that adding iv lidocaine to the iv midazolam + fentanyl drug combination does not provide additional benefit in psa for anterior shoulder reduction. previous studies had indicated the effectiveness of intraarticular prescription of lidocaine in decreasing the pain following shoulder reduction. in this regard, a meta-analysis in 2009 showed that using intra-articular lidocaine is a safe and effective method compared to old methods (22). in the present study, combination of midazolam + fentanyl alone has a high efficiency in sedation of patients and the pain score of the patients has reduced 7.7 points on average (between 4 and 10 points) (table 2). therefore, using iv lidocaine prescription in combination with these drugs could not provide more effectiveness. in a study, kim et al. showed that prescription of 1.5 mg/kg lidocaine as a bolus and single-dose iv injection and continuing it as 2 mg/kg in each hour leads to a significant decrease in pain and reduction in the amount of fentanyl used compared with normal saline group after lumbar microdiscectomy (24). the reason for the difference between the results of that study and the present study can be the continuous infusion of lidocaine in the study by kim et al., while in the present study only a single bolus dose was prescribed. this major difference has led to contradicting results. the evidence for this statement is hidden in the treatment mechanism of lidocaine infusion. iv infusion of the mentioned drug with 1-2 mg/kg dose per hour maintains the plasma concentration of the mentioned drug at a level that is not toxic and provides sympathomimetic and analgesic effects (25) an effect that is not seen in the single-dose strategy. in addition to the effectiveness of a treatment regimen, its adverse side-effects are also of special importance. the findings of the present study indicate that the prevalence of sideeffects after prescription of midazolam + fentanyl is not significantly different from midazolam + fentanyl + lidocaine group. in addition, number needed to harm calculated for triple-drug regimen was 25 patients. however, the major difference between the 2 drug regimens in manifestation of side-effects was observed regarding spo2<90%. since simultaneous prescription of iv lidocaine and fentanyl leads to intensification of fentanyl side-effects, especially depression of central nervous system, the reason for the difference observed regarding hypoxia between the 2 groups can be sought in the interference of lidocaine with the effects of fentanyl. however, hypoxia is a common side-effect in procedural sedations. for example, a meta-analysis showed that hypoxia is the most important side-effect of using sedation and its prevalence is 40.2 people in every 1000 cases. this sideeffect is immediately relieved with prescription of oxygen and is therefore easily managed in emergency departments (6). one of the limitations of the present study is its short follow-up duration. shoulder reduction is a painful procedure and in many cases, after the half-life of sedative drugs passes, pain restarts and troubles the patient. the half-lives of drugs used vary; therefore, if the patients would be followed for a longer period of time (not just until they were completely conscious) the findings might have been different. 5. conclusion findings of the present study showed that addition of a bolus and single-dose of iv lidocaine to the combination of iv midazolam + fentanyl does not provide additional analgesia and sedation in reduction of anterior shoulder dislocation in patients presenting to the emergency department. 6. appendix 6.1. acknowledgements this article derived from aida mohammadianâăźs residency thesis to gain specialty in the field of emergency medicine. all the staff members of the emergency department of imam this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. arhami dolatabadi et al. 6 hospital are thanked for their cooperation throughout the study period. 6.2. author contribution all authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 6.3. funding/support none. 6.4. conflict of interest the authors declare that there is no conflict of interest in any phase of performing the study. references 1. chalidis b, sachinis n, dimitriou c, papadopoulos p, samoladas e, pournaras j. has the management of shoulder dislocation changed over time? international orthopaedics. 2007;31(3):385-9. 2. kanji a, atkinson p, fraser j, lewis d, benjamin s. delays to initial reduction attempt are associated with higher failure rates in anterior shoulder dislocation: a retrospective analysis of factors affecting reduction failure. emerg med j. 2015:emermed-2015-204746. 3. tezel o, kaldirim u, bilgic s, deniz s, eyi ye, ozyurek s, et al. a comparison of suprascapular nerve block and procedural sedation analgesia in shoulder 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procedural sedation and analgesia in the emergency department: a randomized, prospective, double-blind trial. academic emergency medicine : official journal of the society for academic emergency medicine. 2011;18(8):800-6. 17. raeyat doost e, heiran mm, movahedi m, mirafzal a. ultrasound-guided interscalene nerve block vs procedural sedation by propofol and fentanyl for anterior shoulder dislocations. am j emerg med. 2017;35(10):1435-9. 18. challapalli v, tremont-lukats iw, mcnicol ed, lau j, carr db. systemic administration of local anesthetic agents to relieve neuropathic pain. the cochrane database of systematic reviews. 2005(4):cd003345. 19. de oliveira cm, issy am, sakata rk. intraoperative intravenous lidocaine. revista brasileira de anestesiologia. 2010;60(3):325-33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e24 20. groudine sb, fisher ha, kaufman rp, jr., patel mk, wilkins lj, mehta sa, et al. intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. anesthesia and analgesia. 1998;86(2):235-9. 21. koppert w, weigand m, neumann f, sittl r, schuettler j, schmelz m, et al. perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. anesthesia and analgesia. 2004;98(4):1050-5, table of contents. 22. hames h, millard wm. use of intra-articular lidocaine as analgesia in anterior shoulder dislocation: a review and meta-analysis of the literature. canadian journal of rural medicine. 2009;14(4):145. 23. binnekade jm, vroom mb, de vos r, de haan rj. the reliability and validity of a new and simple method to measure sedation levels in intensive care patients: a pilot study. heart & lung : the journal of critical care. 2006;35(2):137-43. 24. kim k-t, cho d-c, sung j-k, kim y-b, kang h, song ks, et al. intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar surgery: a doubleblinded, randomized, placebo-controlled clinical trial. the spine journal. 2014;14(8):1559-66. 25. fitzpatrick bm, mullins me. intravenous lidocaine for the treatment of acute pain in the emergency department. clinical and experimental emergency medicine. 2016;3(2):105. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency (2013); 1 (1): ***-*** this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 1 emergency (2013); 1 (1): 1-6 original research utilization of failure mode and effects analysis (fmea) method in increasing the revenue of emergency department; a prospective cohort study ali shahrami1, farhad rahmati2*, hamid kariman1, behrooz hashemi2, majid rahmati3, alireza baratloo2, mohammad mehdi forouzanfar2, saeed safari2 1. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of management, faculty of economics and administrative science, university of mazandaran, sari, iran abstract introduction: the balance between revenue and cost of an organization/system is essential to maintain its survival and quality of services. emergency departments (ed) are one of the most important parts of health care delivery system. financial discipline of eds, by increasing the efficiency and profitability, can directly affect the quality of care and subsequently patient satisfaction. accordingly, the present study attempts to investigate failure mode and effects analysis (fmea) method in identifying the problems leading to the loss of ed revenue and offer solutions to help fix these problems. methods: this prospective cohort study investigated the financial records of ed patients and evaluated the effective errors in reducing the revenue in ed of imam hossein hospital, tehran, iran, from october 2007 to november 2009. the whole department was divided into one main system and six subsystems, based on fmea. the study was divided into two phases. in the first phase, the problems leading to the loss of revenue in each subsystem were identified and weighted into four groups using risk priority number (rpn), and the solutions for fixing them were planned. then, in the second phase, discovered defects in the first phase were fixed according to their priority. finally, the impact of each solution was compared before and after intervention using the repeated measure anova test. results: 100 financial records of ed patients were evaluated during the first phase of the study. the average of ed revenue in the six months of the first phase was 73.1±3.65 thousand us dollars/month. 12 types of errors were detected in the predefined subsystems. ed revenue rose from 73.1 to 153.1, 207.06, 240, and 320 thousand us dollars/month after solving first, second, third, and fourth priority problems, respectively (337.75% increase in two years) (p<0.001). 111.0% increase in the ed revenue after solving of first priority problems revealed that they were extremely indispensable in decreasing the revenue (p<0.0001). conclusion: the findings of the present study revealed that fmea could be considered as an efficient model for increasing the revenue of emergency department. according to this model, not recording the services by the nursing unit, and lack of specific identifying code for the patients moving from ed to any other department, were the two first priority problems in decreasing our ed revenue. key words: organizational productivity; failure mode and effects analysis method; emergency services; financial management; cost saving cite this article as: shahrami a, rahmati f, kariman h, et al. utilization of failure mode and effects analysis (fmea) method in increasing the revenue of emergency department: a prospective cohort study. emergency. 2013;1(1):1-6. introduction:1 alance between revenue and cost of an organization/system is essential to maintain its survival and quality of services (1). emergency departments (ed) with a large number of annual visits are one of the most important parts of health care delivery system (2-4). financial discipline of ed can directly affect the quality of care and subsequently patient satisfaction by increasing efficiency and profitability of the department (5, 6). in this context, finding an efficient method *corresponding author: farhad rahmati; department of emergency medicine, shohadaye tajrish hospital, tajrish square, tehran, iran. tel/fax: +982122721155 email: f.rahmati2000@yahoo.com received: 1 september 2013; accepted: 25 november 2013 for identifying defects and failures, which decrease the revenue and increase the cost, has a high priority. failure mode and effects analysis (fmea) is one of the methods for identification and analysis of failures and errors (7-12). early and continuous application of this method in the process of designing, allows managers to depict failures and reach a reliable, secure and customer-friendly management model (12). the application of fmea in healthcare systems was first investigated in the 1990s. it was mainly used to avoid errors in medical therapies and became so popular in the second half of this decade (12, 13). accordingly, the present study attempts to investigate fmea in identifying the problems leading to ed revenue loss and offer solutions to help fix these problems. b http://www.jemerg.com/ http://www.ncbi.nlm.nih.gov/mesh/68005376 http://www.ncbi.nlm.nih.gov/mesh/68005376 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 2 shahrami et al methods: study design and setting this prospective cohort study investigated the financial records of ed patients and evaluated the effective errors in reducing revenue in ed of imam hossein hospital (with an average of 4500 visits/month), tehran, iran, throughout an about 24-month period, from october 2007 to november 2009. a workgroup (consisting of the head of ed, head of the insurance office, head of the nursing office, and the study researchers), was established to find financial problems and offer solutions. based on fmea, the whole department was divided into one main system and 6 subsystems: reception unit, nursing unit, medical unit, secretarial unit, discharge unit, and insurance unit. in order to have a clear view on the defects of each subsystem, data was collected through three main methods. i) regular and focused meetings with the personnel working in the subsystem and compiling defect reports; ii) regular meetings with the staff of the next subsystem to identify the problems in the preceding subset based on the analyzed files; and iii) random selection and analysis of files by the authors, in the presence of the related personnel. according to the designed protocol, the researchers along with each subsystem’s personnel investigated the files and then, gave them to the personnel in the next subsystem. they were asked to find the problems and give suggestions to remove them. the solutions for removing the defects were also clarified with the help of the expert panel in medical economy. in these solutions, the responsibility of each subsystem and the period required to obtain the results were assigned. in addition, a supervising unit was planned to evaluate all parts of the process. study details the study was performed in two phases: first phase: in this phase, the defects in the subsystems were detected and prioritized according to fmea. this phase was carried out during the first six months of the study (october 2007 to april 2008). each defect was weighed based on its impact on the final product of the system. this weight was called risk priority number (rpn) and calculated through the following formula: rpn= severity × diagnosis probability × detection degree severity coefficient was defined as the impact of the parameter on revenue. according to the probable impact of each defect on the revenue, a coefficient between 1 and 3 was assigned. these assignments were based on: (1) no financial loss even if the defect is continuous, (2) possibility of financial loss because of the present defect and (3) definite financial loss with the continual presence of the defect. diagnosis probability coefficient was defined so that the score was 1, if the defect was diagnosed through one method of data collection (mentioned above), 2 if it was diagnosed through two of them, and if all three methods diagnosed the defect, the score was 3. detection degree coefficient was defined using the frequency of the defects, so that if incidence of defect was 1 to 10 times per month, the assigned score was 1; 2 was assigned to 11 to 20 times, and if the number exceeded 20 time per month the score would be 3. then, defects with rpn> 15 were put into the first priority category; rpn between 6 and 15 into the second priority; rpn 4 to 6 in the third priority; and rpn< 4 into the fourth priority problems. second phase: in this phase, discovered defects in the first phase were fixed according to their priority during april 2008 to september 2009. finally, the impact of each solution was evaluated before and after the interventions. statistical analysis the collected data were put into spss 21.0 statistical software and after ensuring that all parameters were normal, the impact of each solution was rated using repeated measures anova test before and after interventions. p<0.05 was considered as the level of significance. results: 100 financial records of ed patients were evaluated during the first phase of the study. a close evaluation of the revenue of the ed revealed that the average revenue was 73.1±3.65 thousand us dollars per month in the six months of the first phase. findings of first phase 12 types of errors were detected in the six predefined subsystems as: 1) accepting patients with expired insurance credit by the reception unit. 2) not recording the services by the nursing unit. 3) lack of coordination between nursing reports and the doctor's prescriptions. 4) not recording medical procedures by physicians. 5) incomplete recording of procedures by physicians. 6) ambiguous outpatient physicians' prescriptions on insurance files. 7) physicians' prescriptions with no or illegible dates on insurance files. 8) partial documentation of services by secretarial unit; 9) lack of final control on patients’ files by secretarial unit. 10) late sending of the patients’ files to the discharge unit. 11) lack of specific identifying code for the patients’ files moving from the ed to any other department. 12) late sending of the patients’ files to the agents of the insurance companies. http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 3 emergency (2013); 1 (1): 1-6 table 1: frequency and priority of errors present in each subsystem  subsystem error rpn1 frequency reception accepting patients with expired insurance credit 6 7 (7%) nursing not recording the services 27 23 (23%) lack of coordination between the nursing reports and the doctor's prescriptions 4 10 (10%) medical not recording the medical procedures 12 12 (12%) incomplete recording of procedures 4 8 (8%) ambiguous outpatient prescriptions on insurance files 4 9 (9%) prescriptions without or with illegible dates on insurance files 6 8 (8%) secretarial partial documentation of services 6 6 (6%) lack of final control on patients’ files 4 4 (4%) late sending of the files to the discharge unit 2 4 (4%) discharge lack of specific identifying code for the patients files moving from the ed to any other department 27 100 (100%) insurance late sending of the patients' file to the agents of the insurance companies 2 6 (6%) 1. risk priority number table 2: suggested solutions offered to fix errors based on their priority  priority error suggested solutions first 1not recording the services by nursing unit 2lack of specific identifying code for the patients moving from the ed to any other department 1close control over the input and output services through the ed's store house 2-holding the head of the shift responsible 3-simplification of computer registration in the agenda 4-assigning a separate section (code) for emergency services in the accounting software second 1not recording the medical procedures 2prescriptions with no or illegible dates on the insurance file 3incomplete recording of procedures 4accepting patients with expired insurance credit 1explaining the direct effects of ed revenue on the personnel's income 2rebuking the faulty personnel and reducing their pensions in case there is a problem with the expiration of the insurance or the files sent 3similar rebuking or encouragement policies for the department's secretaries 4returning the illegible or invalid prescriptions on insurance files to the faculty members for fixing 5nursing system is directly responsible for recording the procedures followed by doctors while recording the services 6residents' pensions are directly affected by their performance third 1late sending of the files to the discharge unit 2late sending of the files to the agents of the insurance companies 1giving the responsibility of sending files of each shift to the secretary of the same shift 2coordination between the accounting office and the insurance systems fourth 1lack of coordination between the nursing reports and the doctors' prescriptions 2partial documentation of services by secretarial unit 3ambiguous outpatient prescriptions on insurance files 4lack of final control on patients’ files 1random revision of nursing reports with the attendance of the head of the shift and resident 2returning prescriptions on insurance files with ambiguous seals to the faculty members for fixing the problems before sending to the insurance unit 3controlling the used services of residents by faculty members 4controlling the recording of services used by residents while recording the nursing report 5promotional and instructional classes for the secretaries for a final control before sending the files to the insurance unit http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 4 shahrami et al table 1 demonstrates the frequency and priority of errors in each subsystem. the third subsystem (medical unit) with its four errors has the highest rate of errors. findings of second phase the solutions offered to fix the above-mentioned errors are demonstrated in table 2. the period needed to solve the problems was three months for each priority (sum: 12 months). first priority problems not recording the services by nursing unit and lack of specific identifying code for the patients moving from ed to any other department, were the two first priority problems. implementing the solutions offered in table 2 raised the ed revenue to 153.1 thousand us dollars per month at the end of july 2008. repeated measure anova showed a significant increase of revenue (111.0%) during april to july 2008 (df= 1, 7; f= 456.5, p<0.0001). second priority problems not recording the medical procedures by physicians, physicians' prescriptions with no or illegible dates on insurance files, incomplete recording of procedures by physicians, and accepting patients with expired insurance credit by the reception unit were the four second priority problems. interventions made according to table 2 induced a great increase in the revenue. at the end of october 2008, the ed revenue rose to be 207.06 thousand us dollars per month. this 35.4% raise was significant as well (df= 1, 7; f= 199.6, p <0.0001). third priority problems late sending of the patients' files to the discharge unit and late sending of the patients' file to the agents of the insurance companies were the two third priority problems. by solving these problems, the ed revenue experienced a 15.9% increase and reached 240 thousand us dollars per month. this showed a significant difference compared to october 2008 (df= 1, 7; f= 83.2, p<0.0001). fourth priority problems lack of coordination between the nursing reports and doctors' prescriptions, partial documentation of services by secretarial unit, ambiguous outpatient physicians' prescriptions on insurance files, and lack of final control on patients’ files by secretarial unit were fourth priority problems. by enacting the solutions, the revenue experienced a 33.3% increase and reached 320 thousands us dollar per month at the end of september 2009 (df= 1, 7; f= 112.5, p<0.0001). in summary, ed revenue rose from 73.1 thousand us dollars per month to 153.1 after first priority problems solving, 207.06 after second priority, 240 after third priority, and 320 at the end of the study [(32073.1/73.1) ×100=337.75%](p<0.001). maximum increase in revenue occurred after solving first (111.0%), second (35.4%), fourth (33.3%), and third (15.9%) priority problems, respectively. figure 1 reveals the trend of revenue changes during the second phase of study figure 1: trend of revenue changes during the study period. a-b: first phase, b-g: second phase (b-c: solving of first priority problems, c-d: solving of second priority problems, d-e: solving of third priority problems, e-f: study temporarily stopped, fg: solving of fourth priority problems) g-h: two months observation.  http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 5 emergency (2013); 1 (1): 1-6 period. as figure 1 shows, between the points e and f, the ed revenue reduces and in the mid may 2009, it reaches 211.76 thousand us dollars per month (1, 7;f= 72.6, p<0.0001). this could be explained by a temporarily delay in the study due to closing the trauma department and reduction in the number of the admitted patients. also, in late november 2009, the revenue did not differ greatly compared to late september 2009 (df= 1, 7; f= 0.11, p=0.74). in these two months of observation, the revenue of the ed was 317.64 thousand us dollars/month (p>0.05). discussion: findings of the present study revealed that proper management in the financial system and its subsystems is potentially able to change a fruitless entity into a profitable one. identifying and solving errors in the financial system of the ed in this study increased the revenue by 337.75% in two years. implementing the solutions rose ed revenue from 73.1 thousand us dollars per month to 153.1 after first priority problems solving, 207.06 after second priority, 240 after third priority, and 320 at the end of the study. 111.0% increase in the ed revenue after solving of first priority problems revealed that the above-mentioned problems were extremely indispensable in decreasing the revenue. decreasing the admitted patients and closing the trauma department led to pausing the study after solving third priority problems. this could be the reason for the surprising rise in revenue after solving fourth priority problems. application of fmea in this study revealed the fact that this system is not only applicable in industrial contexts, but also useful in medical finance and increases the profitability of these systems. the study also demonstrated that fmea model is an efficient method in recognizing the errors in medical systems. for instance, sheble et al. using this model, found approximately 100 errors in prescription of antibiotics, and monitored them. they stated that although this method has a high efficiency, healthcare systems should not rely merely on it in order to guarantee their patients' immunity (14). robinson et al. demonstrated that application of this model decreased prescription of wrong drugs by 9% in chemotherapy patients and increased enforcement of standard procedures by 54%. they believed that computerized registration of the medicine is one of the most important measures that could be taken to elevate the efficiency in the system (15). kim et al. showed that fmea model decreased therapeutic errors in children under chemotherapy. they had similar findings and suggested that computerized registration had a positive effect on decreasing errors (16). wetterneck et al. investigated the efficiency of this model in prescription of intravenous medications and concluded that fmea is extremely efficient in identifying potential problems (17). several other available studies demonstrate the efficiency of fmea in decreasing the error rate in medicine and healthcare systems (8, 18, 19). the authors of the present study failed to find any studies on the efficiency of this model in increasing the revenue or decreasing the loss in healthcare organizations. however, a comparison between the findings of this study and other studies concerning the efficiency of fmea model and revealed the huge compatibility between them. similar studies have also demonstrated that application of fmea optimizes the services offered to patients and increase the efficiency. limitation it could be thought that the difference in the number of the patients increased the revenue in the ed. however, it should be noted that the number of patients did not differ significantly in the study period. on the other hand, there is a 10% increase in tariffs of the healthcare services according to the law enforced by the iranian ministry of health. because the increase found in this study is far more than the 10% imposed by the government, the authors believe that the reason of increase is the measure taken by authors. lack of control group was another limitation of the present study. it is recommended that, in future studies, fmea be used to fix problems in other departments to ensure its reliability and validity. conclusion: the findings of the present study revealed that fmea could be considered as an efficient model for increasing the revenue in the ed. according to this model, not recording the services by nursing unit and lack of specific identifying code for the patients' files, moving from ed to any other department, were the two first priority problems in decreasing our ed revenue. acknowledgements: the authors would like to thank all the emergency unit personnel and the staff of the medical statistics center of imam hossein hospital. conflict of interest: the authors declare that there are no conflicts of interest. funding: none authors’ contribution: all authors contribute in drafting/revising the manuscript, study concept or design, analysis or interpretation of data. references: 1. pines jm, batt rj, hilton ja, terwiesch c. the financial consequences of lost demand and reducing boarding in hospital emergency departments. ann emerg med. 2011; 58(4):331-40. 2. geelhoed gc, de klerk nh. emergency department overcrowding, mortality and the 4-hour rule in western australia. med j aust. 2012;196(2):122-6. http://www.jemerg.com/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ 6 shahrami et al 3. richardson db. increase in patient mortality at 10 days associated with emergency department overcrowding. med j aust. 2006;184(5):213. 4. trzeciak s, rivers e. emergency department overcrowding in the united states: an emerging threat to patient safety and public health. emerg med j. 2003;20(5):402-5. 5. eng tr, maxfield a, patrick k, deering mj, ratzan sc, gustafson dh. access to health information and support. jama. 1998;280(15):1371-5. 6. russell s, gilson l. user fee policies to promote health service access for the poor: a wolf in sheep's clothing? int j health serv. 1997;27(2):359-79. 7. bonfant g, belfanti p, paternoster g, et al. clinical risk analysis with failure mode and effect analysis (fmea) model in a dialysis unit. j nephrol. 2010;23(1):111-7. 8. cinque m, coronato a, testa a. a failure modes and effects analysis of mobile health monitoring systems. innovations and advances in computer, information, sstems sciences, and engineering: springer; 2013. p. 569-82. 9. freitag m, carroll vs. handoff communication: using failure modes and effects analysis to improve the transition in care process. qual manage healthcare. 2011;20(2):103-9. 10. khare rk, nannicelli ap, powell es, seivert np, adams jg, holl jl. use of risk assessment analysis by failure mode, effects, and criticality to reduce door-to-balloon time. an emerg med. 2013;62(4):388-98. 11. wilkinson da, kolar md. failure modes and effects analysis applied to high-dose-rate brachytherapy treatment planning. brachytherapy. 2013; 12(4): 382–6. 12. williams e, talley r. the use of failure mode effect and criticality analysis in a medication error subcommittee. hosp pharm. 1994;29(4):331-7. 13. derosier j, stalhandske e, bagian jp, nudell t. using health care failure mode and effect analysis: the va national center for patient safety's prospective risk analysis system. jt comm j qual patient saf. 2002;28(5):248-67. 14. shebl n, franklin b, barber n, burnett s, parand a. failure mode and effects analysis: views of hospital staff in the uk. j health serv res policy. 2012;17(1):37-43. 15. robinson dl, heigham m, clark j. using failure mode and effects analysis for safe administration of chemotherapy to hospitalized children with cancer. jt comm j qual patient saf. 2006;32(3):161-6. 16. kim gr, chen ar, arceci rj, et al. error reduction in pediatric chemotherapy: computerized order entry and failure modes and effects analysis. arch pediatr adolesc med. 2006;160(5):495. 17. wetterneck tb, skibinski ka, roberts tl, et al. using failure mode and effects analysis to plan implementation of smart iv pump technology. am j health syst pharm. 2006;63 (16):1528-38. 18. franklin bd, shebl na, barber n. failure mode and effects analysis: too little for too much? bmj qual saf. 2012;21(7): 607-11. 19. hernandez b, bravo c, esteban m, et al. grp-073 failure mode and effect analysis in improving the safety of the chemotherapy process. eur j hosp pharm sci pract 2013;20 (suppl 1):a26-a7. http://www.jemerg.com/ emergency. 2018; 6 (1): e4 or i g i n a l re s e a rc h pro-bnp versus meds score in determining the prognosis of sepsis patients; a diagnostic accuracy study majid shojaee1, saeed safari2, anita sabzghabaei2, mostafa alavi-moghaddam1, ali arhami dolatabadi1, hamid kariman1, soheil soltani1∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical science, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical science, tehran, iran. received: november 2017; accepted: december 2017; published online: 15 january 2018 abstract: introduction: pro-brain natriuretic peptide (pro-bnp) can act as an independent predictor of mortality in septic patients. this study aimed to compare the diagnostic accuracy of pro-bnp and mortality in emergency department sepsis (meds) score in this regard. methods: this cross-sectional study was conducted on > 14 years old sepsis patients of an emergency department (ed), during 2 years. the level of pro-bnp and meds score were measured for all eligible patients and considering one month mortality as reference, screening performance characteristics of the two tests were compared using spss 21 and stats 11. results: 121 patients with the mean age of 75.87±11.82 years were studied (55.4% male). 85 (70.25%) patients had moderate to high probability of mortality according to meds score. the mean pro-bnp levels of survivor and non-survivor patients were 489.69 ± 327.47 and 3954.98 ± 2717.85 pg/ml, respectively (p < 0.0001). sensitivity and specificity of pro-bnp (in 1000 pg/ml cut off ) and meds score (in level 3) in prediction of 1-month mortality were 93.6 (83.7-97.9), 94.8 (84.7-98.6), 65.0 (51.9-76.3), and 98.2 (89.5-99.9), respectively. area under the roc curve of the two tests were 97.36 (95% ci: 92.92-94.48) and 92.31 (95% ci: 86.35-96.53), respectively (p = 0.0543). conclusion: pro-bnp and meds score both have excellent diagnostic accuracy in predicting 1-month mortality of sepsis patients. however, considering the higher sensitivity as well as availability and ease of calculation, it seems that pro-bnp can be considered an appropriate tool for screening patients with high risk of mortality following sepsis in ed. keywords: pro-brain natriuretic peptide; sepsis; mortality; emergency department; dimensional measurement accuracy © copyright (2018) shahid beheshti university of medical sciences cite this article as: shojaee m, safari s, sabzghabaei a, alavi-moghaddam m, arhami dolatabadi a, kariman h, soltani s. pro-bnp versus meds score in determining the prognosis of sepsis patients; a diagnostic accuracy study. emergency. 2018; 6(1): e4. 1. introduction s eptic response is in fact a chain of inflammatory and anti-inflammatory processes and hormone-cell reactions that manifest clinically via systemic disorders such as: shock, myocardial disorder, activation of coagulation system and disseminated endothelial injury (1-4). based on the report of world health organization (who), in united states of america more than 1 million people are affected with sepsis, about half of which lose their lives and sepsis is the third cause of mortality after heart diseases and cancers (5, 6). timely identification of patients at risk of mortal∗corresponding author: soheil soltani; emergency department, imam hossein hospital, imam hossein square, shahid madani avenue, tehran, iran. email: soheil_soltani@yahoo.com tel: 00989122196632 ity due to sepsis can be helpful in selecting type of intervention, treatment protocol, diagnostic method, and probably improve their final outcome (7-9). mortality in emergency department sepsis (meds) score is an acceptable scale for predicting the prognosis of sepsis, which is not commonly used nowadays due to having many variables and its calculation being time consuming (10). currently, biomarkers such as: pro-bnp, lactate, crp, d-dimer, pro-calcitonin and troponin are considered for determining the prognosis of patients with sepsis (11-13). natriuretic peptides are used in diagnosis and risk stratification of patients with acute coronary syndrome and congestive heart failure but the role of these factors in prognosis and diagnosis of patients with septic shock is still under debate (14). natriuretic peptides play an important role in maintenance of cardiovascular homeostasis and circulating blood volume. pro-bnp is secreted in response to stretching in the atrium or ventricle wall or due to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. shojaee et al. 2 myocardial ischemia in 2 shapes of n-terminal pro-bnp (ntpro bnp) and c-terminal peptide (bnp) (15, 16). it has been shown that pro-bnp can act as an independent predictor of mortality in patients with cardiac shock, septic shock, and severe sepsis (17-23). however, this marker has not been able to predict short-term mortality in critically ill patients hospitalized in critical care unit with hypoxic respiratory failure (24). therefore, in search for finding an accurate as well as easy and available scale for replacing meds score in emergency department (ed), the present study was designed with the aim of evaluating the diagnostic value of pro-bnp in comparison with meds score in determining the prognosis of sepsis patients ed. 2. methods 2.1. study design and setting the present study is a prospective cross-sectional one that was designed and performed with the aim of determining the diagnostic accuracy of pro-bnp in predicting the prognosis of patients with sepsis in ed of imam hossein hospital, tehran, iran, from september 2014 to march 2016. protocol of this study was approved by the ethics committee of shahid beheshti university of medical sciences and the researchers adhered to the principles indicated in the declaration of helsinki regarding medical ethics. before entering the study, the patient or their relative signed an informed written consent for participating in the study. the research team did not interfere in the diagnostic and treatment processes of the patients. 2.2. participants patients over the age of 14 years with sepsis presenting to the ed were randomly included in the study. for random sampling, cases were selected on random days (these days were randomly selected on the first day of each month). simultaneous presence of systemic inflammatory response syndrome (sirs) criteria and definitive evidence of infection based on american college of chest physicians/society of critical care medicine consensus was considered as the definition of sepsis (25). patients with diagnosis of sepsis, severe sepsis, or septic shock were included in the study. cases with history of proven cardiac or kidney failure, electrocardiogram (ecg) indicating new cardiac problems and children were excluded from the study. 2.3. data gathering demographic data (age, sex), source of infection (pneumonia; urinary tract infection; digestive disease; bedsore and . . . ), variables needed for calculation of meds score (10), serum level of pro-bnp on admission as well as 1-month outcome of the patients regarding mortality were gathered for all the patients via a pre-designed checklist. source of infection was determined according to the final decision of the in charge physician and considering all the laboratory, imaging, and clinical evidence. pro-bnp measurement was done using 1cc of the patient’s venous blood sample drawn on admission for measuring other laboratory parameters ordered by the in charge physician. blood drawing was done by a laboratory technician who was not aware of the study. pro-bnp level measurement was done via chemilumenescence sandwich immunoassay using elecsys 2010 kit, roche diagnostic, mannheim, germany. the kit was a high-quality and rapid (taking 18 minutes) kit that finally reports pro-bnp rate as pg/cc. to calculate meds score, a medical calculator named emcalculator was used and according to the results the patients were divided into 5 groups regarding mortality risk: very low, low, moderate, high, and very high. finally, the mortality status of the patients 30 days after admission to ed was followed and recorded via phone calls. it should be noted that treatment of sepsis patients in the mentioned center is done according to the protocol of surviving sepsis campaign by emergency service with consultation of infection service (26). one emergency medicine resident was in charge of data gathering, calculating meds score and follow up of patients by phone. 2.4. statistical analysis minimum sample size required for the present study considering 95% confidence interval, 80% power, 7% error, and 0.63 area under the receiver operating characteristic (roc) curve of pro-bnp (27), was calculated to be 122 cases. data were analyzed via spss 21 and stata 11 software. qualitative data were reported as frequency and percentage, and quantitative data as mean ± standard deviation (sd). finally, for determining the diagnostic accuracy of pro-bnp in predicting the 1-month prognosis of sepsis patients, roc curve was drawn and the best cut-off was calculated. in addition, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios with 95% confidence interval were calculated and reported using vassarstats medical calculator. to compare the diagnostic accuracies of the 2 tests in predicting the risk of 1-month mortality in patients with sepsis presenting to the ed, comparison of area under the roc curve was done via chi square test. in all analyses p<0.05 was considered as level of significance. accuracy of 0.90-0.100 was considered as excellent, 0.80-0.90 as good, 0.70-0.80 as fair, 0.60-0.70 as poor, and 0.50-.60 as fail. 3. results 3.1. baseline characteristics 155 patients were candidates for entering the study, 9 (5.80%) were excluded due to history of kidney failure and 7 (4.52%) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e4 figure 1: mean and standard deviation of patients’ pro-bnp level based on their meds score level. figure 2: area under the receiver operating characteristic (roc) curve of pro-bnp and meds score in determining the risk of 1month mortality among sepsis patients in emergency department (p=0.0543). due to cardiac failure. in addition, 18 (11.61%) were excluded due to missing data and problem in follow-up. finally, 121 patients with the mean age of 75.87±11.82 (20-98) years were evaluated (55.4% male). table 1 shows the baseline characteristics of the patients. 85 (70.25%) patients had moderate to high probability of mortality according to meds scale. the mean pro-bnp levels of survivor and non-survivor patients were 489.69 ± 327.47 and 3954.98 ± 2717.85 pg/ml, respectively (p < 0.0001). figure 1 depicts mean pro-bnp level based on the patients’ meds score. 3.2. screening performance characteristics of all the studied patients, 63 (52.1%) died after 1 month. area under the roc curve of pro-bnp and meds score in prediction of 1-month mortality of sepsis patients admitted to ed were 97.36 (95% ci: 92.92-94.48) and 92.31 (95% ci: 86.35-96.53), respectively (p = 0.0543, figure 2). according to the area under the roc curve, the best cut off to predict 1month mortality was 1000 pg/ml for pro-bnp and level 3 for table 1: baseline characteristics of studied patients variable number (%) sex male 67 (55.4) female 54 (44.6) age (year) 20 40 3 (2.5) 40 60 7 (5.8) ≥ 60 111 (91.7) source of infection pneumonia 49 (40.5) urinary tract infection 45 (37.2) digestive problem 14 (11.6) bedsore 6 (4.9) multiple sources 7 (5.8) meds score 1 21 (17.4) 2 15 (12.4) 3 43 (33.5) 4 15 (12.4) 5 27 (22.3) pro-bnp (pg/ml) < 1000 59 (48.8) ≥ 1000 62 (51.2) data are reported as frequency and percentage. meds scale. table 2 shows the screening performance characteristics of meds score and pro-bnp in the mentioned cut offs. 3.3. discussion: based on the findings of the present study, pro-bnp over 1000 pg/ml and meds scale both have excellent diagnostic accuracy in predicting 1-month mortality of sepsis patients. however, considering the higher sensitivity of pro-bnp (93.6 vs. 65.0) as well as availability and ease of calculation, it seems that pro-bnp can be considered an appropriate tool for screening patients with high risk of mortality following sepsis in ed. presently, various tools have received attention for determining the prognosis of critically ill patients (26, 28, 29). in a study by varpula et al. in 2007, it was shown that pro-bnp changes in the first 3 days of hospitalization is a good prognostic scale in septic patients (19). in kimmoun et al. study in 2013 pro-bnp level directly correlated with the hemodynamic changes of septic patients (30). a comparison regarding increase in pro-bnp among cardiac patients and sepsis patients showed a significant increase in the level of this marker in sepsis or septic shock patients compared to cardiac patients (31). in carpenter et al. study, it was shown that 44% of those with sepsis or septic shock have levels of systolic disorders and in line with this finding they deemed higher serum bnp levels in these patients associated with worse outcome (32). another study has also suggested the concentration of this biomarker on the 5th day after hospithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. shojaee et al. 4 table 2: screening performance characteristics of pro-bnp in 1000 pg/ml cut-off and meds score in level 3 (moderate to high risk of death) characteristics pro-bnp meds true positive 59 41 true negative 55 57 false positive 3 1 false negative 4 22 sensitivity 93.6 (83.7-97.9) 65.0 (51.9-76.3) specificity 94.8 (84.7-98.6) 98.2 (89.5-99.9) positive predictive value 95.2 (85.6-98.7) 97.6 (85.9-99.8) negative predictive value 93.2 (82.7-97.8) 72.2 (60.8-81.4) positive likelihood ratio 19.66 (6.51-59. 3) 41.0 (5.9-284. 4) negative likelihood ratio 0.07 (0.02-0.18) 0.3 (0.2-0. 5) measures are presented with 95% confidence interval. talization as an index for prognosis of critically ill patients with a higher risk of mortality (33). on the other hand, accuracy of meds score in prediction of 1-month risk of mortality for sepsis patients has been evaluated and declared in numerous studies. kuo et al. studied 431 patients with pyogenic liver abscesses and affirmed the high accuracy of this scale in this regard (34). another study in 2003 introduced this scale as a proper tool for triage and making decisions regarding treatment of sepsis patients (10). a study in netherlands in 2012 indicated the higher power of this scale compared to biomarkers such as crp and lactate in prediction of 28-day mortality of sepsis patients in ed (35). area under the roc curve of meds score in this regard was estimated to be 0.81 in a study by macdonald et al. (36). considering all the mentioned points as well as some other important points including ease of calculation, availability, higher sensitivity, and similar accuracy and specificity it seems that pro-bnp can be considered a more beneficial tool compared to meds score in prediction of mortality risk and screening of patients with sepsis in ed. it is obvious that doing this screening can help in concentrating the treatment system on more critically ill patients and using more rigorous diagnostic and treatment modalities in trying for improving their outcome. however, it should be noted that in developing countries such as iran pro-bnp measurement is still expensive and it might appear not cost effective to do this evaluation for all sepsis patients. yet it should be taken into account that proper allocation of funds leads to overall decrease in treatment costs and improvement of patients’ outcome. 3.4. limitations not differentiating the patients with sepsis, severe sepsis, and septic shock can be one of the limitations of this study. it might have been better to differentiate these patients and evaluate the diagnostic accuracy of the tests in each of the 3 groups to improve the overall accuracy of the study. 4. conclusion based on the findings of the present study, pro-bnp and meds score both have excellent diagnostic accuracy in predicting 1-month mortality of sepsis patients. however, considering the higher sensitivity as well as availability and ease of calculation, it seems that pro-bnp can be considered an appropriate tool for screening patients with high risk of mortality following sepsis in ed. 5. appendix 5.1. acknowledgements this study is extracted from dr. soheil soltani’s thesis for achieving the specialist degree in emergency medicine. the emergency department staff members of imam hossein hospital are acknowledged for their effort and cooperation throughout the study. 5.2. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. 5.3. funding/support no funds have been received for carrying out this project. 5.4. conflict of interest the authors declare that there is no conflict of interest regarding the present study. references 1. gullo a, bianco n, berlot g. management of severe sepsis and septic shock: challenges and recommendations. critical care clinics. 2006;22(3):489-501. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e4 2. hotchkiss rs, karl ie. the pathophysiology and treatment of sepsis. new england journal of medicine. 2003;348(2):138-50. 3. landry dw, oliver ja. the pathogenesis of vasodilatory shock. new england journal of medicine. 2001;345(8):588-95. 4. lee wl, slutsky as. sepsis and endothelial permeability. the new england journal of medicine. 2010;363(7):689. 5. 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acute heart failure*. critical care medicine. 2006;34(8):2140-4. 32. charpentier j, luyt c-e, fulla y, vinsonneau c, cariou a, grabar s, et al. brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis. critical care medicine. 2004;32(3):660-5. 33. post f, weilemann ls, messow c-m, sinning c, mãijnzel t. b-type natriuretic peptide as a marker for sepsisinduced myocardial depression in intensive care patients. critical care medicine. 2008;36(11):3030-7. 34. kuo sh, lee yt, li cr, tseng cj, chao wn, wang ph, et al. mortality in emergency department sepsis score as a prognostic indicator in patients with pyogenic liver abscess. am j emerg med. 2013;31(6):916-21. 35. hermans m, leffers p, jansen l, keulemans y, stassen p. the value of the mortality in emergency department sepsis (meds) score, c reactive protein and lactate in predicting 28-day mortality of sepsis in a dutch emergency department. emerg med j. 2012;29(4):295-300. 36. macdonald sp, arendts g, fatovich dm, brown sg. comparison of piro, sofa, and meds scores for predicting mortality in emergency department patients with severe sepsis and septic shock. academic emergency medicine. 2014;21(11):1257-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e6 or i g i n a l re s e a rc h 3-month outcome of ischemic stroke patients underwent thrombolytic therapy; a cohort study payam sariaslani1, shahab rezaeian2,3, elham safari1∗ 1. neurology department, faculty of medicine, kermanshah university of medical sciences, kermanshah, iran. 2. infectious diseases research center, kermanshah university of medical sciences, kermanshah, iran. 3. clinical research development center, imam reza hospital, kermanshah university of medical sciences, kermanshah, iran. received: october 2019; accepted: december 2019; published online: 25 january 2020 abstract: introduction: reperfusion and neuroprotection are 2 main treatment strategies exist for management of patients with ischemic stroke. this study aimed to assess the 3-month outcome of patients who underwent thrombolytic therapy following ischemic stroke. methods: in the present prospective cohort study, the 3-month outcome of patients (mortality, disability) with acute ischemic stroke admitted to neurology department an educational hospital, kermanshah, iran, from 2016 to 2019, who had received thrombolytic therapy was assessed. national institute of health stroke scale (nihss) and modified rankin score (mrs) were used for measuring the degree of disability (on admission, at the time of discharge and 3 months after thrombolytic therapy). results: 217 patients with the mean age of 66.40 ± 13.37 (27 – 97) years were studied (55.3% male). there was no significant correlation between decrease in nihss score and age (p = 0.44), sex (p = 0.082), time interval between initiation of symptoms (p = 0.104), and blood pressure on admission (p = 0.156). however, patients with blood sugar lower than 144 had better 3-month outcome (p = 0.045). additionally, there was no significant correlation between the rate of decrease in mrs score and age (p = 0.813), sex (p = 0.875), time interval between initiation of symptoms (p = 0.495), and blood pressure on admission (p = 0.264). however, patients with blood sugar lower than 144 had better 3-month outcome (p = 0.022). 47 (21.7%) patient died and 170 (78.3%) were discharged. mean age of the patients who died (73.70 ± 11.85 versus 64.39 ± 13.09 years; p < 0.0001) and their nihss score on admission (13.22 ± 6.01 versus 11.28 ± 5.70; p = 0.045) were significantly higher. in other words, the odds of mortality was 3.19 times in patients over 60 years of age (95% confidence interval (ci): 1.18 – 8.62) and 1.83 times in patients with nihss score over 12 (95% ci: 0.92 – 3.61). conclusion: there was no significant correlation between 3-month disabilities of stroke patients underwent thrombolytic therapy and age, sex, time from initiation of symptoms, or vital signs on admission. patients with a blood sugar lower than 144 had better 3-month outcome. keywords: tissue plasminogen activator; stroke; brain ischemia; stroke rehabilitation cite this article as: sariaslani p, rezaeian sh, safari e. 3-month outcome of ischemic stroke patients underwent thrombolytic therapy; a cohort study. arch acad emerg med. 2020; 8(1): e6. 1. introduction stroke is the most common cause of disability and the third cause of mortality following cardiac diseases and cancer around the world. the most common type of stroke is the ischemic type. each year about 700 thousand stroke patients are visited in the united states, 600 thousand of which are ischemic. mortality rate of stroke is about 12% and each year ∗corresponding author: elham safari; neurology department, imam reza hospital, kermanshah, iran. tel: 00989183662796 email: eli_safari1989@yahoo.com 7.8 million people die of stroke all around the world and the chance of an individual having a stroke over his/her lifetime is 18%. previous investigations have shown that 70 – 80% of deaths due to brain stroke happen in ischemic ones (1, 2). previously, the incidence of brain stroke among the youth was 3%; of course, this group included individuals less than 45 years of age. however, currently it can be said that this rate has increased to 7% or 8% in the same age group. from a clinical point of view, brain stroke is associated with many kinds of problems including alterations in level of consciousness, physical, motor, cognitive, and perceptual disorders, reduced linguistic performance, pain, and psychological disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. sariaslani et al. 2 orders such as depression. this has decreased improvement and rehabilitation among these patients and might even lead the patient to suicide (3). physiologically, brain stroke is a syndrome confirmed by acute initiation of neurological disorders persisting for at least 24 hours and is a reflection of the central nervous system being locally affected and is a result of deficiency in the brain’s blood circulation (4, 5). the aim of most existing treatments is restoring blood circulation in the ischemic penumbra area, which is the region that cells are not functional due to ischemia but if the blood circulation is restored, they will be revitalized (6, 7). overall 2 treatment strategies exist for this disease, namely reperfusion and neuroprotection (4, 5). the most appropriate treatment presented for acute ischemic brain stroke is using arterial and venous tissue plasminogen activator (tpa) (8, 9). ideally, more than 40% of all brain stroke patients should receive recombinant tpa (rtpa) (10-12). the present study aimed to assess the 3-month outcome of patients who underwent thrombolytic therapy following ischemic brain stroke. 2. methods 2.1. study design and setting in the present prospective cohort study, the 3-month outcome of patients with acute ischemic stroke admitted to neurology department of imam reza hospital, kermanshah, iran, from 2016 to 2019, who had received thrombolytic therapy was assessed. the study was approved by the ethics committee of kermanshah university of medical sciences (ethics code: ir.kums.rec.1397.642) and the researchers adhered to the principles indicated in the declaration of helsinki throughout the study. before the injection of drug and inclusion in the study, written consent was obtained from the patient or their relatives. 2.2. participants all patients over 18 years of age presenting to the mentioned hospital with acute ischemic stroke, for which thrombolytic drugs were prescribed, were included. those with hemorrhagic brain stroke, individuals for whom receiving thrombolytic drugs was contraindicated, patients whose time of stroke was unknown or had presented outside the window period of receiving thrombolytic drugs as well as those who did not give consent for participation in the study or were not available for 3-month follow-up studies were excluded from the study. 2.3. data gathering a checklist consisting of demographic data (age, sex, weight), the route of transportation to hospital, interval between initiation of symptoms to hospital presentation, underlying illnesses, blood pressure and blood sugar levels on admission, drug history, history of heart attack, national institute of health stroke scale (nihss) and modified rankin score (mrs) (on admission, at the time of discharge and 3 months after thrombolytic therapy), duration of hospitalization, and in-hospital mortality was filled out for all of the patients by a senior neurology resident. all the patients were re-evaluated using nihss and mrs scores 3 months after thrombolytic therapy. to invite the patients for examination 3 months later, they were contacted via phone and were invited to the clinic. 2.4. outcome the evaluated outcomes in the present study consisted of 3month mortality and disability of the patients and nihss and mrs indices were used to perform the evaluations. 2.5. tpa injection method the precise time of initiation of the first symptom (including dysarthria, hemiparesis, and . . . ) was asked from the patients or their relatives and a thorough history was taken regarding heart attack, stroke, and medications used as well as risk factors including hypertension, diabetes, and smoking. blood examinations including glucometry and brain computed tomography (ct) scan were also performed. in case of hypertension, respiratory disorder and hemodynamic instability, the patient was stabilized first. if hemorrhage was not detected in brain ct scan and no contraindication was present, thrombolytic injection was done. the dose of the drug was 0.9 mg/kg body weight, 10% of which was administered as a bolus dose and the rest was infused over 1 hour. in the present study, the medication used was alteplase manufactured by boehringer ingelheim company. all injections were done under complete cardiorespiratory monitoring and direct supervision of the in-charge neurologist. in addition, all the ct scans were also interpreted by the in-charge neurologist. 2.6. nihss it is used to evaluate the effect of acute brain stroke on level of consciousness, language, attention, field of vision, eye movement, muscular power, speech, sensory function, and ataxia. this scale has 15 items that should be graded based on neurological examination. based on the patient’s answers and ability to move in each item, the examiner gives the patient a final score ranging from 0 to 42, in which zero indicates being normal (13). 2.7. mrs a useful tool for measuring the degree of disability and dependence in the daily activities of those who suffer from brain damage. validity and reliability of this scale has been this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e6 proved. the score range of this tool is 0 to 6. score of 0 indicates absence of any sign of neurological damage. score of 1 shows that the patient does not have a considerable disability and is able to do his/her regular activities and duties. score of 2 means that the patient has mild disability and cannot perform tasks like before, but can take care of him/herself without help. score of 3 indicates that the patient has moderate disability and needs help, but can walk without any help. score of 4 shows that the patient has relatively severe disability and cannot walk without help, and cannot survive without help. score of 5 means that patient has relatively severe disability and is bedridden, has incontinence and requires constant care and nursing. score of 6 indicates death of the patient (14-16). 2.8. statistical analysis extracted data were entered to spss software version 21 and underwent statistical analysis. quantitative variables were reported as mean and standard deviation, and qualitative ones were reported as frequency and percentage. t test, chisquare and fisher exact tests were used for comparisons. p < 0.05 considered as level of significance. 3. results 3.1. baseline characteristics of the studied patients 217 patients with the mean age of 66.40 ± 13.37 (27 – 97) years and average weight of 70.74 ± 11.99 (50 – 120) kg were studied (55.3% male). table 1 depicts the baseline characteristics of the studied patients. mean time interval between initiation of the symptoms and presentation to the hospital was 112.75 ± 58.24 (15 – 240) minutes. in addition, mean blood sugar of the patients was 138.82 ± 65.59 mg/dl (using glucometer) on admission. mean time interval between admission and receiving thrombolytic therapy was estimated to be 39.02 ± 19.4 (8 – 120) minutes. 3.2. outcomes on average, patients were hospitalized for 13.25 ± 13.48 (174) days. mean nihss (p < 0.001) and mrs (p < 0.001) scores had significantly improved at the time of discharge and 3 months after the treatment (table 2). there was no significant correlation between decrease in nihss score and age (p = 0.44), sex (p = 0.082), time interval between initiation of symptoms and presenting to the hospital (p = 0.104), and blood pressure on admission (p = 0.156). however, there was a significant correlation between decrease in nihss score in patients and blood sugar under 144; patients with blood sugar lower than 144 had better 3-month outcome (p = 0.045). additionally, there was no significant correlation between the rate of decrease in mrs score and age (p = 0.813), table 1: baseline characteristics of studied patients variable value sex male 120 (55.3) female 97 (44.7) age (year) < 60 53 (24.4) ≥ 60 164 (75.6) route of transportation to hospital personal vehicle 162 (74.7) ambulance 115 (25.3) symptom initiation to reaching hospital (minute) ≤ 180 183 (84.3) > 180 34 (15.7) blood pressure on admission (mmhg) systolic 146.10 ± 24.48 diastolic 89.17 ± 18.1 history of disease hypertension 144 (73.0) diabetes 25 (11.5) brain stroke 23 (10.6) hyperlipidemia 6 (2.8) atrial fibrillation 19 (8.8) smoking no 194 (89.4) yes 23 (10.6) coagulant use no 194 (89.4) yes 23 (10.6) disability on admission nihss 11.69 ± 5.81 mrs 2.72 ± 1.9 data are presented as frequency (%) or mean ± standard deviation. nihss: national institute of health stroke scale; mrs: modified rankin score. sex (p = 0.875), time interval between initiation of symptoms and presenting to the hospital (p = 0.495), and blood pressure on admission (p = 0.264). however, there was a significant correlation between decrease in mrs score in patients and blood sugar under 144; patients with blood sugar lower than 144 had better 3-month outcome (p = 0.022). 47 (21.7%) patient died and 170 (78.3%) were discharged. mean age of the patients who died (73.70 ± 11.85 versus 64.39 ± 13.09 years; p < 0.0001) and their nihss score on admission (13.22 ± 6.01 versus 11.28 ± 5.70; p = 0.045) were significantly higher. in other words, the odds of mortality was 3.19 times in patients over 60 years of age (95% confidence interval (ci): 1.18 – 8.62) and 1.83 times in patients with nihss score over 12 (95% ci: 0.92 – 3.61). 4. discussion based on the findings of the present study, the rate of inhospital mortality of patients with brain stroke undergoing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. sariaslani et al. 4 table 2: mean scores of the patients in national institute of health stroke scale (nihss) and modified rankin score (mrs) indices on admission, at the time of discharge and 3 month after treatment index time of measurement p on admission discharge 3 months later nihss 11.69 ± 5.81 6.35 ± 4.61 5.47 ± 4.48 < 0.001 mrs 2.72 ± 1.9 2.47 ± 1.32 2.18 ± 1.44 < 0.001 thrombolytic therapy was estimated to be about 22% and age over 60 years and nihss over 12 on admission were the significant risk factors of death. there was no significant correlation between 3-month outcome of the patients regarding disability based on nihss and mrs indices and demographic data (age and sex), time from initiation of symptoms, or vital signs on admission. patients with a blood sugar lower than 144 had better 3-month prognosis based on the mentioned scales. in 2016, baratloo et al. showed that 30% of the brain stroke patients who met the criteria of thrombolytic therapy had received rtpa in iran. high cost of rtpa and lack of proper infrastructure were mentioned as the major obstacles for thrombolytic therapy in that study (17). the results of dong et al. (2015), which were in line with the present study, indicated that mean nihss and mrs scores and hospitalization duration significantly decreased in patients with ischemic stroke who received venous tpa (18). this finding has also been confirmed in the study by tosta et al. (19). mehta et al. (2017) also presented results in line with the present study, indicating that in 3-month follow-up, an acceptable improvement is found in 67% of patients receiving rtpa. 32% of the patients deteriorated and severity of symptoms on admission, blood sugar on admission, age and type of stroke affected the outcome of patients (20). in the study by albers et al. (2000) the rate of 30-day mortality was 13% among patients receiving rtpa, 35% of the patients had considerably improved and had mrs scores less than 1 and 43% of them were independent in their daily activities and had mrs scores less than 2. patients with initial nihss over 10 showed less improvement and there was a significant correlation between increase in the patient’s blood pressure on admission and decrease in probability of improvement (21). however, in the present study no significant correlation was found between patients’ blood pressure on admission and the rate of improvement in 3-month outcome. the reason for the differences in factors found to affect the outcome of stroke patients in various studies could be differences in duration of follow-up, baseline characteristics of the studied patients, race, medications used, and care provided after thrombolytic therapy. on the other hand, in these studies it is often not known if the patients have undergone rehabilitation and physiotherapy or not and therefore, to reach better conclusions, further controlled studies might be needed. considering the results of the present study, it seems that paying more attention to patients with higher risk and screening them, providing more care and more regularly monitoring them may be effective in decreasing their mortality. however, it should be noted that based on the findings of the present study and other existing studies, most introduced risk factors affecting the outcome of these patients such as age, underlying illness, blood pressure, and etc. cannot be controlled by the physician. therefore, in this regard, the best level of prevention might be the primary level, which is controlling non-contagious diseases such as hypertension and diabetes. 5. limitation small sample size, being single centered, short duration of the follow-up period, and not checking other factors affecting patients’ outcome such as presence or absence of rehabilitation are among the limitations of the present study. 6. conclusion based on the findings of the present study, the rate of inhospital mortality of patients with brain stroke undergoing thrombolytic therapy was estimated to be about 22% and age over 60 years and nihss over 12 on admission were the only significant risk factors of death. there was no significant correlation between 3-month outcome of the patients regarding disability based on nihss and mrs indices and demographic data (age and sex), time from initiation of symptoms, or vital signs on admission. patients with a blood sugar lower than 144 had better 3-month prognosis based on the mentioned scales. 7. declarations 7.1. acknowledgements the personnel of neurology and emergency departments of imam reza hospital are thanked for their cooperation throughout the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 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of the four score coma scale in a pediatric population. journal of neuroscience nursing. 2009;41(5):261-7. 15. eken c, kartal m, bacanli a, eray o. comparison of the full outline of unresponsiveness score coma scale and the glasgow coma scale in an emergency setting population. european journal of emergency medicine. 2009;16(1):29-36. 16. lyden pd. thrombolytic therapy for stroke: springer science & business media; 2001. 17. baratloo a, forouzanfar mm, hashemi b, safari s, kasmaei hd, rouhipour a, et al. tissue plasminogen activator: a literature review. archives of neuroscience. 2016;3(1). 18. dong y, cao w, ren j, nair ds, parker s, jahnel jl, et al. vascular risk factors in patients with different subtypes of ischemic stroke may affect their outcome after intravenous tpa. plos one. 2015;10(8):e0131487. 19. tosta ed, rebello lc, almeida ss, neiva mss. treatment of ischemic stroke with r-tpa: implementation challenges in a tertiary hospital in brazil. arquivos de neuro-psiquiatria. 2014;72(5):368-72. 20. mehta a, mahale r, buddaraju k, majeed a, sharma s, javali m, et al. intravenous thrombolysis for acute ischemic stroke: review of 97 patients. journal of neurosciences in rural practice. 2017;8(1):38. 21. albers gw, bates ve, clark wm, bell r, verro p, hamilton sa. intravenous tissue-type plasminogen activator for treatment of acute stroke: the standard treatment with alteplase to reverse stroke (stars) study. jama. 2000;283(9):1145-50. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e11 or i g i n a l re s e a rc h frequency and causes of complaints against emergency medicine specialists in forensic medicine files; a crosssectional study hossein alimohammadi1, hamidreza hatamabadi1, azita khodayari2, mahmood doukhtehchi zadeh azimi1∗ 1. emergency department, imam hossein hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. office of tehran province forensic medicine commissions, tehran, iran. received: october 2018; accepted: december 2018; published online: 27 january 2019 abstract: introduction: complaints against physicians have increased in recent years and one of the specialties facing a relatively high rate of complaints is emergency medicine. therefore, the present study was designed with the aim of evaluating the frequency and causes of complaints against emergency medicine specialists in forensic medicine cases. methods: in the present cross-sectional study, all the existing files in two forensic medicine centers, tehran, iran, from 2012 to 2015, in which complaints were filed against emergency medicine specialists, either alone or along with other physicians, were evaluated via census sampling method and their required data were extracted and recorded via a pre-designed checklist. results: 151 cases of medical complaints were filed against emergency medicine specialists during the study period. 85 (53.6%) complaints were filed following death of the patients and 66 (43.7%) were filed following an injury or disability. multiple trauma, stomach ache, and altered level of consciousness were the most common chief complaints among young and old patients upon their ed visit. in 104 (68.9%) cases, the emergency medicine specialists were finally proved innocent. no significant correlation was found between the probability of proving innocent and the physician’s experience (p = 0.92), physician’s sex (p = 0.27), age range of the patient (p = 0.193), or the shift in which the patient had visited the ed (p = 0.32). the rate of proving innocent was significantly higher in complaints against governmental hospitals compared to non-governmental ones (73.6% vs. 61.9%; p= 0.004) and teaching hospitals compared to non-teaching ones (75.8% vs. 54.9%; p = 0.26). conclusion: in about 70% of medical complaint cases against emergency medicine specialists, the in charge physician was proved innocent. no significant correlation was found between the probability of proving innocent and physician’s experience, the physician’s sex, the patient’s age range, or the shift in which the patient had presented to the ed. keywords: emergency medicine; medical errors; malpractice; forensic medicine cite this article as: alimohammadi h, hatamabadi h, khodayari a, doukhtehchi zadeh azimi m. frequency and causes of complaints against emergency medicine specialists in forensic medicine files; a cross-sectional study. arch acad emerg med. 2019; 7(1): e11. 1. introduction emergency medicine is one of the young branches of specialty in medicine in which specialists are at a high risk of committing medical errors and malpractice and facing probable complaints due to it. more than 75% of emergency medicine specialists encounter these kinds of complaints at some point in their career (1). studies have shown that emer∗corresponding author: mahmood doukhtehchi zadeh azimi; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. tel: 00989352105930 email: azimimahmood@hotmail.com gency department (ed) is one of the most vulnerable departments to medical errors (2). ed is a special unit in which numerous and complex factors are at play, which make it potentially error prone (3). emergency medicine specialty is in the third place regarding frequency of complaints in forensic medicine after obstetrics and gynecology, and orthopedics (4). adverse outcomes caused by malpractice strongly correlate with complaints and financial penalties (5, 6). for reducing the risk, 9 out of every 10 physicians use excessive drug precautions and diagnostic methods known as defensive medicine, which leads to an annual cost of 46 million dollars in the united states (7, 8). fear of complaint can cause stress, depression, and reduction in the ability of effective this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. alimohammadi et al. 2 communication with the patient in the individual providing service (9, 10). of course, in many complaints the issue has been unavoidable or affected by factors out of the physician’s control (9). various methods exist for assessing patient safety such as hospital committees, periodical meetings of risk management, autopsy reports and reviewing the complaints filed in legal authorities (11). being aware of the number and types of complaints filed against emergency physicians as well as the evaluations performed by the board of judges can be of help in planning for preventing and reducing errors. therefore, the present study has been designed with the aim of evaluating the frequency and causes of complaints against emergency medicine specialists in forensic medicine files. 2. methods 2.1. study design and setting the present study is a cross-sectional study performed on the complaints filed against active emergency medicine specialists in tehran province in 2 centers of western tehran forensic medicine center and office of tehran province forensic medicine commissions, tehran, iran, from 2012 to 2015. protocol of the present study was approved by ethics committee of shahid beheshti university of medical sciences and researchers adhered to confidentiality of the evaluated files. 2.2. participants all the files related to complaints against emergency medicine specialists in forensic medicine centers of tehran province were evaluated via census method. no limitation was considered regarding age, sex or job experience in the present study. in these files, the emergency medicine specialist was either one of the individuals, or the only person questioned regarding the probability of medical error or malpractice. 2.3. data gathering by referring to the archives of 2 centers, western tehran forensic medicine center and office of tehran province forensic medicine commissions, all the cases in which complaints were filed against emergency medicine specialists alone or along with other physicians were extracted. then, using a pre-designed checklist, the required data including age and sex of the patient, chief complaint of the patient, cause of complaint against physicians, the result of evaluations performed by the board of forensic medicine judges, age and sex and job experience of the emergency medicine specialist and type of hospital (teaching or non-teaching) were extracted and recorded. the person in charge of gathering data was a senior emergency medicine resident under the supervision of an emergency medicine specialist. figure 1: the frequency of medical complaints filed against emergency medicine specialists based on the studied years. 2.4. statistical analysis demographic characteristics were evaluated via descriptive statistics tests (frequency, mean and . . . ). chi-square and student’s t-test statistical analyses were used for performing comparisons and p-values less than 0.05 were considered significant. all the analyses were done using spss software version 18. 3. results 151 cases of medical complaints were filed against emergency medicine specialists during the study period (39.7% against an emergency medicine specialist alone). mean age of the patients in the mentioned files was 47.13 ± 21.62 (295) years (63.6% male). table 1 has summarized the characteristics of the studied files. 85 (53.6%) complaints were filed following death of the patients and 66 (43.7%) were filed following an injury or disability. 121 (80.1%) cases were filed in governmental hospitals and 99 (56.5%) in teaching hospitals. figure 1 has depicted the frequency of complaints based on the studied years. 3.1. outcome of the evaluated files in 104 (68.9%) cases, the emergency medicine specialists were finally proved innocent. the highest and lowest penalties considered for the physicians involved in the files were 5% and 45% of maximum penalty for murder. no significant correlation was found between the probability of proving innocent and the physician’s experience (p = 0.92), physician’s sex (p = 0.27), age range of the patient (p = 0.193), or the shift in which the patient had visited the ed (p = 0.32). the rate of proving innocent was significantly higher in complaints against governmental hospitals compared to nongovernmental ones (73.6% vs. 61.9%; p= 0.004) and teaching hospitals compared to non-teaching ones (75.8% vs. 54.9%; p = 0.26). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e11 table 1: characteristics of the evaluated files in the present study variable frequency (%) sex male 96 (63.6) female 55 (36.4) age < 18 8 (5.3) 18 – 60 92 (60.9) > 60 51 (33.8) chief complaint trauma 53 (35.1) stomach ache 26 (17.2) altered level of consciousness 15 (9.9) general weakness 10 (6.6) chest pain 9 (6.0) shortness of breath 9 (6.0) other 29 (19.2) time of presentation to ed morning sift (7 – 19) 89 (59.0) night shift (19 – 7) 62 (41.0) complaint against emergency medicine alone 69 (39.7) multiple services 82 (84.3) type of hospital governmental 121 (80.1) non-governmental 30 (19.9) teaching hospital yes 99 (56.5) no 52 (43.5) ed: emergency department 4. discussion based on the findings of the present study, in about 70% of medical complaint cases against emergency medicine specialists, the in charge physician was proved innocent. no significant correlation was found between the probability of proving innocent and physician’s experience, the physician’s sex, the patient’s age range, or the shift in which the patient had presented to the ed. cases of governmental and teaching hospitals had a significantly higher percentage of proving innocent compared to others. studies have shown that currently we are faced with medical error crisis all over the world; as the number of complaints filed against the healthcare providing staff of hospitals is increasing in the united states and europe, which is in turn associated with an increase in financial loss due to penalties (12-16). in this study, most complaints were filed against governmental and teaching hospitals. one of the reasons for complaints against emergency physicians working in governmental and university hospitals being more frequent can be that currently most emergency medicine specialists are working in these types of hospitals and their activities in non-governmental hospitals is much less than governmental hospitals. thus, it is natural for the rate of complaints against governmental hospitals to be higher than non-governmental hospitals. however, despite the higher rate of complaints against these hospitals, the rate of proving innocent was significantly higher in governmental and teaching hospitals. in the present study, in about 70% of the complaints, the physician was proved innocent. in a study by sadr et al. on orthopedics specialists also 61% of the cases led to the physicians proving innocent (17). this finding is in line with other studies performed on the subject of medical errors in iran. in most of these studies, the physicians who were sued were proved innocent in the end in 60% to 80% of cases (18, 19). in the present study, in 56% of the cases the reason for filing a complaint was death of the patient. this finding was also observed in the study by gupta et al. (20), in which complaints due to death of the patient had a significantly higher rate compared to other complaints. multiple trauma, stomach ache, and altered level of consciousness were the most common chief complaints among young and old patients upon their ed visit. however, other complaints such as chest pain, shortness of breath and weakness were also very common and require more attention from emergency physicians at the time of examining patients. alongside these cases, patients with laceration should be pointed out. patients with laceration who visit the ed for its repair are among the most common patients in the ed, which have also recorded one of the highest rates of filing complaints against physicians, and physicians in ed need to apply scientific points and practical skills with more accuracy when encountering them and document the measures taken and explanations done to the patient with more care. in the study by hwang et al. it was revealed that the most common diagnoses leading to complaints were infectious diseases, malignancies, and leg fractures. the study has analyzed complaints on medical errors in taiwan for 12 years. the differences in the results can be due to the results of the current study being limited to the emergency department and different cultures of the 2 countries (4). another chief complaint that should be considered is loss of consciousness in elderly patients. patients over the age of 65 years will be affected with altered level of consciousness with any small problem, which might be mistaken with amnesia or emotional disturbances in the elderly and finally lead to death or serious damage to the patient. therefore, it is necessary that physicians in the ed evaluate these patients with more precision. misdiagnosing the disease is one of the most common, most costly and the most dangerous medical errors (21). in a recent report, complaint due to misdiagnosis was on the top of the list of complaints related with malpractice in the united states (16). finally, it should be noted that training emergency medicine specialists regarding cases leading to medical errors in order to prevent recurrence of similar errors, planning the shifts of emergency medicine specialist in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. alimohammadi et al. 4 a manner that they have enough down time for recovery, providing necessary equipment for ed, aiding in facilitation of patient turnover, employing enough nursing and service providing staff, and providing continuous education for increasing the scientific knowledge of emergency medicine specialists could be among the possible solutions for effectively reducing the prevalence and frequency of medical errors in ed. 5. limitation in the present study, only medical errors that have led to a complaint are evaluated, while at least part of them are never detected by the patients or their relatives or are not filed for complaints. therefore, the results of the present study only reflect the part of medical errors that have led to a complaint. a more analytical evaluation of systematic errors that lead to medical errors has not been performed in the present study, which can be the subject of future studies. 6. conclusion based on the findings of the present study, in about 70% of medical complaint cases against emergency medicine specialists, the in charge physician was proved innocent. no significant correlation was found between the probability of proving innocent and physician’s experience, the physician’s sex, the patient’s age range, or the shift in which the patient had presented to the ed. cases of governmental and teaching hospitals had a significantly higher percentage of proving innocent compared to others. 7. appendix 7.1. acknowledgements this article has been derived from dr. mahmoud doukhtehchi’s thesis for achieving his specialist degree in emergency medicine from shahid beheshti university of medical sciences. 7.2. author contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors’ orcids hamidreza hatamabadi: 0000-0002-9085-8806 hossein alimohammadi: 0000-0002-3556-5066 7.3. funding/support none. 7.4. conflict of interest none. references 1. jena ab, seabury s, lakdawalla d, chandra a. malpractice risk according to physician specialty. new england journal of medicine. 2011;365(7):629-36. 2. carrier er, reschovsky jd, mello mm, mayrell rc, katz d. physicians’ fears of malpractice lawsuits are not assuaged by tort reforms. health affairs. 2010;29(9):158592. 3. croskerry p, sinclair d. emergency medicine: a practice prone to error? canadian journal of emergency medicine. 2001;3(4):271-6. 4. hwang c-y, wu c-h, cheng f-c, yen y-l, wu k-h. a 12-year analysis of closed medical malpractice claims of the taiwan civil court: a retrospective study. medicine. 2018;97(13):e0237-e. 5. chandra a, nundy s, seabury sa. the growth of physician medical malpractice payments: evidence from the national practitioner data bank: the growth of malpractice payments is less than previously thought. health affairs. 2005;24(suppl1):w5-240-w5-9. 6. studdert dm, mello mm, gawande aa, gandhi tk, kachalia a, yoon c, et al. claims, errors, and compensation payments in medical malpractice litigation. new england journal of medicine. 2006;354(19):2024-33. 7. bishop tf, federman ad, keyhani s. physicians’ views on defensive medicine: a national survey. archives of internal medicine. 2010;170(12):1081-3. 8. mello mm, chandra a, gawande aa, studdert dm. national costs of the medical liability system. health affairs. 2010;29(9):1569-77. 9. carlson jn, foster km, pines jm, corbit ck, ward mj, hydari mz, et al. provider and practice factors associated with emergency physicians’ being named in a malpractice claim. annals of emergency medicine. 2018;71(2):157-64. e4. 10. gallagher th, waterman ad, ebers ag, fraser vj, levinson w. patients’ and physicians’ attitudes regarding the disclosure of medical errors. jama. 2003;289(8):1001-7. 11. cosby ks. a framework for classifying factors that contribute to error in the emergency department. annals of emergency medicine. 2003;42(6):815-23. 12. gaynor m, seider h, vogt wb. the volume-outcome effect, scale economies, and learning-by-doing. american economic review. 2005;95(2):243-7. 13. neale fr, eastman kl, peterson drake p. dynamics of the market for medical malpractice insurance. journal of risk and insurance. 2009;76(1):221-47. 14. toth f. sovereigns under siege. how the medical profession is changing in italy. social science & medicine. 2015;136:128-34. 15. buzzacchi l, scellato g, ughetto e. frequency of medical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e11 malpractice claims: the effects of volumes and specialties. social science & medicine. 2016;170:152-60. 16. schaffer ac, jena ab, seabury sa, singh h, chalasani v, kachalia a. rates and characteristics of paid malpractice claims among us physicians by specialty, 1992-2014. jama internal medicine. 2017;177(5):710-8. 17. sadr ss, ghadyani mh, zadeh b, asghar a. assessment of records of complaints from medical malpractice in the field of orthopedic, in the coroner’s office of forensic medicine, province of tehran, during 1988 to 2003. ijfm. 2007;13(2):78-86. 18. bayazidi s, zarezadeh y, zamanzadeh v, parvan k. medication error reporting rate and its barriers and facilitators among nurses. journal of caring sciences. 2012;1(4):231. 19. asadi p, modirian e, dadashpour n. medical errors in emergency department; a letter to editor. 2018. 2018;6(1):e33. 20. gupta a, snyder a, kachalia a, flanders s, saint s, chopra v. malpractice claims related to diagnostic errors in the hospital. bmj quality &amp; safety. 2018;27(1):53-60. 21. schiff gd, kim s, abrams r, cosby k, lambert b, elstein as, et al. diagnosing diagnosis errors: lessons from a multi-institutional collaborative project. agency for healthcare research and quality rockville md; 2005. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e2 ca s e re p o rt spontaneous retroperitoneal hematoma and membranous glomerulonephritis; a case report foroogh sabzghabaei1∗, mohammad reza babaei2, asaad moradi3, behnam shakiba3 1. department of internal medicine, firoozgar hospital, iran university of medical science, tehran, iran. 2. interventional radiology unit, firoozgar hospital, iran university of medical science, tehran, iran. 3. urology department, firoozgar hospital, iran university of medical science, tehran, iran. received: november 2019; accepted: december 2019; published online: 25 january 2020 abstract: spontaneous retroperitoneal hematoma (srh) is a rare finding which is usually accompanied with anticoagulant and/or antiplatelet aggregation therapy. we describe a patient with a rare presentation of srh and membranous glomerulonephritis with diffuse visceral arterial micro aneurysms due to medium to small size vasculitis and weakly positive antinuclear antibody (ana). to the authors’ knowledge, this is a unique report, which does not have any serologic confirmation of specific vasculitis. keywords: retroperitoneal space; hematoma; glomerulonephritis, membranous cite this article as: sabzghabaei f, babaei m r, moradi a, shakiba b. spontaneous retroperitoneal hematoma and membranous glomerulonephritis; a case report. arch acad emerg med. 2020; 8(1): e2. 1. introduction spontaneous retroperitoneal hematoma (srh) is an uncommon clinical entity, which is usually concomitant with anticoagulant or antiplatelet aggregation use (1). solely, in about 15% of the cases there is no history of these medications, two third of which occur due to vascular causes (1). hereby, we describe a rare case of srh with clinical findings of medium to small size vasculitis without any serologic documentation of a specific disease. 2. case presentation a 58-year-old iranian man presented to the emergency department with the chief complaint of generalized abdominal pain lasting for over an hour with radiation to the lumbar region. he had none of the symptoms of nausea, vomiting and diarrhea. in the first visit, he was afebrile with normal vital signs. on physical examination, his abdomen was soft and not distended; however, mild general abdominal tenderness was recognized. he had no history of other illnesses, trauma and drug abuse. his pain disappeared after an hour without any treatment. ∗corresponding author: foroogh sabzghabaei; nephrology department, firoozgar hospital, valadi st., valiasr ave., tehran, iran. postal code: 1593748711, email: fresh1383@gmail.com, tel: +98-21-82141-301 laboratory test results, which was performed at the time of admission, revealed hemoglobin (hb)= 9 gr/dl (normal: 12-16), erythrocyte sedimentation rate (esr)= 102 mm/h (normal: 0-20), serum creatinine (cr)= 2.5 mg/dl (normal: 0.8-1.3), serum albumin= 2.3 gr/dl (normal :4), serum amylase= 65 u/l (normal<100), lactate dehydrogenase (ldh)= 962 u/ml (normal: 225-500), normal white blood cell count, platelet count, prothrombin and partial thromboplastin time (pt and ptt), and normal aminotransferases level. in urinalysis, urine sediment ph: 5.5, osmolality: 500 mosmol/kg, protein: 4+, wbc: 3-5/hpf, and rbc: 1-2/ hpf was observed. 24-hour urine protein level was 4.8 gram. total abdominal ultrasonography on admission was unremarkable. upper gastrointestinal endoscopy and colonoscopy only revealed a small gastric ulcer with benign pathology. abdominopelvic computed tomography (ct) showed large retroperitoneal hematoma without any connection to visceral organs (figure 1). because there was no history of abdominal trauma or anticoagulant use, abdominal angiography was performed, in which presence of multiple visceral and renal small artery aneurysms was reported (figure 1). although there was no hematoma expansion during admission and the patient’s general condition remained good with stable vital signs, his serum cr increased to 4.8 mg/dl on the 7th day, before contrast medium prescription. the results of an extensive serologic panel for collagen vascular diseases this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. sabzghabaei et al. 2 figure 1: large retroperitoneal hematoma on the first day of admission without connection to any visceral organ (left image), abdominal angiography with multiple pseudo-aneurysms in multiple splanchnic arteries, superior mesenteric artery and its branches, and renal arteries (right image). revealed only a positive antinuclear antibody (ana) =1/160 with speckled pattern. kidney biopsy was performed and treatment with methyl prednisolone (1gr/d for 3 days) and cyclophosphamide was started with the possible diagnosis of medium to small size vasculitis. renal pathology was compatible with membranous and focal crescentic glomerulonephritis. after 8 weeks of treatment his serum cr and urine protein decreased to 1.7 mg/dl and 1200 mg/24h, respectively. these values were 1.4 mg/dl and 235 mg/24h after 6 months. abdominal ct angiography was performed after 8 months, which confirmed the disappearance of all visceral micro aneurysms. 3. discussion we have described a patient who presented to emergency department with srh and membranous glomerulonephritis (mgn) without any laboratory and clinical evidence of any type of vasculitis. srh is an uncommon disease, which is related to anticoagulant or antiplatelet consumption in 85% of the cases (1). in the remaining 15%, the most frequent causes are renal carcinoma and angiomiolipoma, adrenal lesions (2), and rupture of splanchnic arteries aneurysms due to vasculitis (3, 4). multiple aneurysms of splanchnic arteries and renal arteries accompanied with an elevated esr, low albumin, acute kidney injury and proteinuria without any symptoms or signs of infection strongly define systemic vasculitis, especially involving medium to small size vessels (4). wegener, churgstrauss and microscopic polyarteritis nodosa (pan) are the most frequent diagnoses in this category (5). absence of pulmonary involvement, eosinophilia, palpable cutaneous purpura, positive anti neutrophil cytoplasmic antibody (anca), and presence of mgn beside focal crescents make these diagnoses unlikely. the diagnosis of vasculitis is typically made by pathological study, although angiographic findings have also been used frequently (4, 6). a special aspect of our patient was that he had nephrotic range proteinuria and mgn. to our knowledge there is no correlation between pan and mgn (7, 8) and beside a positive ana, systemic lupus erythematous (sle) may be among the differential diagnosis. however, systemic necrotizing vasculitis with aneurysm formation is an uncommon feature of sle (2-4%) and there are only rare reports of sle with splanchnic arteries aneurysm rupture, which have been detected through angiography (9, 10). the patient was treated with immunosuppressive drugs (prednisolone and cyclophosphamide) and a very good response in clinical and para-clinical signs and symptoms was observed after 6 months including cr=1.4, normal complete blood count and esr, more than 50 percent decrease in proteinuria and specifically the disappearance of micro aneurysms; yet, we could not differentiate sle from other systemic vasculitis diseases. fortunately, their treatment plan is almost similar. 4. conclusion membranous glomerulonephritis (mgn) without any laboratory and clinical evidence of any type of vasculitis may be a cause of srh. it should be stated that the present study is a case report and case reports are classified in the low level in the hierarchy of evidence. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e2 5. declarations 5.1. acknowledgements the authors wish to thank dr. toktam moghiman who kindly edited the manuscript. 5.2. authors contribution all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. authors orcids foroogh sabzghabaei: 0000-0002-6819-7079 mohammad reza babaei: 0000-0002-5658-627x asaad moradi: 0000-0002-6909-4573 behnam shakiba: 0000-0002-3945-3803 5.3. ethical consideration the scientific value of presenting this case was fully described to the patient and an informed consent was obtained from him before submission. all procedures performed in the present study were in accordance with the standards of the ethical committee of iran university of medical sciences and the 1964 helsinki declaration. 5.4. conflict of interest authors have no conflict of interest. 5.5. funding none. references 1. caleo o, bocchini g, paoletta s, ierardi am, scionti a, tonerini m, et al. spontaneous non-aortic retroperitoneal hemorrhage: etiology, imaging characterization and impact of mdct on management. a multicentric study. la radiologia medica. 2015;120(1):133-48. 2. zhang jq, fielding jr, zou kh. etiology of spontaneous perirenal hemorrhage: a meta-analysis. the journal of urology. 2002;167(4):1593-6. 3. buresta p, freyrie a, paragona o, d’addato m. ruptured pancreaticoduodenal artery aneurysm: a case report and review of the literature. journal of cardiovascular surgery. 2004;45(2):153-7. 4. bonamigo tp, erling jr n, faccini fp. rupture of a saccular renal artery aneurysm: report of a case. surgery today. 2002;32(8):753-5. 5. daskalopoulos g, karyotis i, heretis i, anezinis p, mavromanolakis e, delakas d. spontaneous perirenal hemorrhage: a 10-year experience at our institution. international urology and nephrology. 2003;36(1):15-9. 6. boersma h, nap r, haanstra w, hooijboer p, van der kleij f. a rare cause of spontaneous perirenal haemorrhage in a patient with anca-associated vasculitis. neth j med. 2013;71(6):318-22. 7. seo p, stone jh. the antineutrophil cytoplasmic antibody–associated vasculitides. the american journal of medicine. 2004;117(1):39-50. 8. stone jh. limited versus severe wegener’s granulomatosis: baseline data on patients in the wegener’s granulomatosis etanercept trial. arthritis & rheumatism: official journal of the american college of rheumatology. 2003;48(8):2299-309. 9. drenkard c, villa a, reyes e, abello m, alarcon-segovia d. vasculitis in systemic lupus erythematosus. lupus. 1997;6(3):235-42. 10. melamed n, molad y. spontaneous retroperitoneal bleeding from renal microaneurysms and pancreatic pseudocyst in a patient with systemic lupus erythematosus. scandinavian journal of rheumatology. 2006;35(6):481-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 95 emergency (2015); 3 (3): 95-98 original research diagnostic accuracy of cincinnati pre-hospital stroke scale behzad zohrevandi, vahid monsef kasmaie, payman asadi*, hosna tajik, nastaran azizzade roodpishi guilan road trauma research center, guilan university of medical sciences, rasht, iran *corresponding author: payman asadi; road trauma research center, guilan university of medical sciences, rasht, iran tel: +989111351340; fax: +983117923445; email: payman.asadi@yahoo.com received: august 2014; accepted: december 2014 abstract introduction: stroke is recognized as the third cause of mortality after cardiovascular and cancer diseases, so that lead to death of about 5 million people, annually. there are several scales to early prediction of at risk patients and decreasing the rate of mortality by transferring them to the stroke center. in the present study, the accuracy of cincinnati pre-hospital stroke scale was assessed. methods: this was a retrospective cross-sectional study done to assess accuracy of cincinnati scale in prediction of stroke probability in patients referred to the emergency department of poursina hospital, rasht, iran, 2013 with neurologic symptoms. three criteria of cincinnati scale including facial droop, dysarthria, and upper extremity weakness as well as the final diagnosis of patients were gathered. sensitivity, specificity, predictive values, and likelihood ratios of cincinnati scale were calculated using spss version 20. results: 448 patients were assessed. the agreement rate of cincinnati scale and final diagnosis was 0.483 ± 0.055 (p<0.0001). the sensitivity of 93.19% (95% cl: 90.11-95.54), specificity of 51.85% (95% cl: 40.4763.10), positive predictive value of 89.76% (95% cl: 86.27-92.62), negative predictive value of 62.69% (95% cl: 55.52-72.45), positive likelihood ratio of 1.94% (95% cl: 1.54-2.43), and negative likelihood ratio of 0.13% (95% cl: 0.09-0.20) were calculated. conclusion: it seems that pre-hospital cincinnati scale can be an appropriate screening tool in prediction of stroke in patients with acute neurologic syndromes. key words: stroke; decision support techniques; facial paralysis; dysarthria; early diagnosis cite this article as: zohrevandi b, monsef kasmaie v, asadi p, tajic h, azizzade roodpishi n. diagnostic accuracy of cincinnati pre-hospital stroke scale. emergency. 2015;3(3):95-8 introduction: troke is recognized as the third cause of mortality after cardiovascular and cancer diseases, so that lead to death of about 5 million people, annually (1). only in united states about 700,000 people each year suffer from stroke or recurrence of it (2). also in iran the rate of stroke in people older than 45 year-old is nearly 338 per 100,000 cases (3, 4). delay in diagnosis may lead to irreversible complications, while with appropriate and timely treatments such outcomes can be decreased, significantly (5). there are different scales to early prediction of stroke events such as cincinnati prehospital stroke scale (cpss), melbourne ambulance stroke screen (mass), medic pre-hospital assessment for code stroke (medic pacs), and los angeles pre-hospital stroke screen (lapss), (6-11). in cincinnati scale, becoming positive of facial droop, dysarthria, or weakness in the upper extremities is considered as a sign of stroke (12). in frendl et al. study in 2009, the sensitivity and specificity of cincinnati scale were reported 94% and 20%, respectively (13). another study in north carolina for comparison of two pre-hospital scales showed higher sensitivity of cincinnati scale than med pacs (about 79%)(11). consequently, using above-mentioned scales can be useful in timely prediction of patients at risk for development of cerebrovascular attacks. so, in this study the accuracy of cincinnati scale was assessed in prediction of stroke among patients hospitalized with neurologic symptoms. methods: study design and setting this retrospective cross-sectional study done to assess the accuracy of cincinnati stroke scale in patients with acute neurologic symptoms referred to the emergency department of poursina hospital, rasht, iran, from april to august 2013. cincinnati scale is a pre-hospital scale to assess the stroke probability with three variables included facial droop, dysarthria, and upper extremity weakness. becoming positive of each variable leads to the positive result of cincinnati scale. this project was s copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com zohrevandi et al 96 confirmed by ethical committee of guilan university of medical sciences. all researchers observed the declaration of helsinki during the study. hospitalized patients with at least one acute neurologic symptom on arrival such as weakness or numbness in limbs, facial numbness, dizziness, dysarthria, aphasia, severe headache with unknown cause, visual impairment, gait abnormality, and ataxia, etc. were entered. data regarding three criteria of cincinnati scale including facial droop, dysarthria, and upper extremity weakness as well as the final diagnosis of patients were gathered (table 1). according to recorded clinical information, the results of brain computed tomography (ct) scan, and responsible neurologist's view, the probability of stroke was finally diagnosed. subsequently, the accuracy of cincinnati scale in estimation of stroke compare to the final diagnosis was assessed. for detecting the agreement rate between cincinnati scale and final diagnosis of the neurologist, kappa coefficient was applied. the rate of agreement was considered as very weak (0-0.2), weak (0.21-0.4), average (0.41-0.6), good (0.61-0.8), and excellent (0.8-1) (14). there was no limitation of age and gender in the present study. statistical analysis data was analyzed by spss version 20 and chi-square test. the total sample volume was estimated as 422 cases with considering 88.77% sensitivity, 10% accuracy, and 95% confidence interval. sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), positive likelihood ration (lr+), and negative likelihood ratio (lr-) were calculated. qualitative variables were reported as percentage and quantitative ones as mean and standard deviation. p<0.05 was considered statistically significant. results: 448 patients who referred to the emergency department with at least one neurologic symptom were assessed. 197 (44%) cases had facial droop, 298 (66.5%) upper extremity weakness, and 198 (44%) dysarthria. among cincinnati variables, facial droop had 0.188 ± 0.032 (p<0.0001), upper extremity weakness 0.270 ± 0.046 (p<0.0001), and dysarthria 0.223 ± 0.031 (p<0.0001) agreement rate with final diagnosis, (table 2). the accuracy of facial droop, upper extremity weakness, and dysarthria were 56.3%, 71.2%, and 58.3%, respectively. in addition, the agreement rate of cincinnati scale and final diagnosis in prediction of stroke was 0.483 ± 0.055 (p<0.0001). finally, the sensitivity of 93.19% (95% ci: 90.11-95.54), specificity of 51.85% (95% ci: 40.47-63.10), ppv of 89.76% (95% ci: 86.27-92.62), table 1: the initial assessment of patients by using pre-hospital cincinnati stroke scale variables normal status abnormal status facial droop both sides of the face move equally one side of the face does not move upper extremity weakness both sides of the upper extremity move equally one side of the upper extremity does not move dysarthria the patient produces speech without any problem the patient has dysarthria table 2: the rate of agreement between cincinnati scale and final diagnosis of patients in prediction of stroke probability variables stroke kappa p yes (%) no (%) total (%) facial droop yes 184 (41.1) 13 (2.9) 197 (44) no 183 (40.8) 68 (15.2) 251 (56) 0.188 ± 0.32 0.0001 upper extremity weakness yes 268 (59.8) 30 (6.7) 298 (66) no 99 (22.1) 51 (11.4) 150 (34) 0.270 ± 0.046 0.0001 dysarthria yes 189 (42.2) 9 (2) 198 (44) no 178 (39.7) 72 (16.1) 250 (56) 0.223 ± 0.031 0.0001 cincinnati positive 342 (76.3) 39 (8.7) 381 (85) negative 25 (6.5) 42 (9.4) 67 (15) 0.483 ± 0.055 0.0001 copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 97 emergency (2015); 3 (3): 95-98 npv of 62.69% (95% ci: 55.52-72.45), lr+ of 1.94% (95% ci: 1.54-2.43), and lrof 0.13% (95% ci: 0.090.20) were calculated for cincinnati scale in prediction of stroke probability (table 3). discussion: the results of this study showed high sensitivity of cincinnati scale for using as an appropriate screening tool in pre-hospital prediction of stroke. in frendl et al. study on sensitivity of cincinnati scale in 2009 the similar results was achieved, but with lesser ppv and specificity as well as higher npv (13). in comparison with studnek et al. study, cincinnati scale had higher sensitivity and specificity in the present study (11). also, in chen et al. study regarding comparison of cincinnati and lapss scales, it was shown that cincinnati has significantly higher sensitivity and lower specificity (6). in the study of mingfeng and colleagues, the pre-hospital scale of rosier had significantly higher specificity and lower sensitivity than cincinnati (15). bray et al. also showed that mass and cincinnati scales have the same sensitivity (7). it seems that cincinnati scale because of high sensitivity can be an appropriate screening tool to rapid and early prediction of stroke in patients with acute neurologic symptoms. thus, by using this scale, these patients can be transferred to hospitals equipped with stroke center and decrease the rate of mortality through this way. performing other studies with more sample volume was suggested to do more accurate assessment. conclusion: based on the findings of present study, it is concluded that pre-hospital cincinnati scale can be an appropriate screening tool in prediction of stroke in patients with acute neurologic syndromes. acknowledgments: this article is derived from thesis of nastaran aziz zadeh roudpishi to give the doctorate degree of medicine from gilan university of medical sciences. we would like to say thanks to vice chancellor for research of medical faculty and those helped us to perform this project. conflict of interest: none funding support: none authors’ contributions: all authors passed criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. luengo-fernandez r, gray am, rothwell pm. effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (express study): a prospective population-based sequential comparison. lancet neurol. 2009;8(3):235-43. 2. lloyd-jones d, adams r, carnethon m, et al. heart disease and stroke statistics—2009 update a report from the american heart association statistics committee and stroke statistics subcommittee. circulation. 2009;119(3):e21-e181. 3. delbari a, salman roghani r, tabatabaei ss, lökk j. a stroke study of an urban area of iran: risk factors, length of stay, case fatality, and discharge destination. j stroke cerebrovasc dis. 2010;19(2):104-9. 4. kasmaei hd, baratloo a, nasiri z, soleymani m, yazdani mo. recombinant tissue plasminogen activator administration in patients with cerebrovascular accident; a case series. archives of neuroscience. 2015;2(2). 5. savitz si, caplan lr, edlow ja. pitfalls in the diagnosis of cerebellar infarction. acad emerg med. 2007;14(1):63-8. 6. chen s, sun h, lei y, et al. validation of the los angeles prehospital stroke screen (lapss) in a chinese urban emergency medical service population. plos one. 2013;8(8):e70742. 7. bray je, coughlan k, barger b, bladin c. paramedic diagnosis of stroke examining long-term use of the melbourne ambulance stroke screen (mass) in the field. stroke. 2010;41(7):1363-6. 8. kidwell cs, saver jl, schubert gb, eckstein m, starkman s. design and retrospective analysis of the los angeles prehospital stroke screen (lapss). prehosp emerg care. 1998;2(4):267-73. 9. kidwell cs, starkman s, eckstein m, weems k, saver jl. identifying stroke in the field prospective validation of the los angeles prehospital stroke screen (lapss). stroke. 2000;31(1):71-6. 10. kothari ru, pancioli a, liu t, brott t, broderick j. cincinnati prehospital stroke scale: reproducibility and validity. ann emerg med. 1999;33(4):373-8. 11. studnek jr, asimos a, dodds j, swanson d. assessing the validity of the cincinnati prehospital stroke scale and the medic prehospital assessment for code stroke in an urban emergency medical services agency. prehosp emerg care. 2013;17(3):348-53. table 3: screening prformance characteristics of cincinnati stroke scale in prediction of stroke probability (95% confidence interval) variables facial droop weakness dysarthria cincinnati sensitivity 50.1 (55.4-44.9) 73.0 (68.2-77.0) 51.5 (46.2-56.7) 93.2 (90.1-95.5) specificity 84.0 (74.11.2) 63.0 (51.5-73.4) 88.9 (80.0-94.8) 51.8 (40.5-63.1) ppv 93.4 (89.0-96.4) 83.9 (85.9-93.1) 95.4 (91.5-97.9) 89.8 (86.3-92.6) npv 27.1 (21.7-33.0) 34 (26.5-42.2) 28.8 (23.3-34.8) 62.7 (55.5-72.4) lr+ 3.10 (1.9-5.2) 2.0 (1.5-2.6) 4.60 (2.5-8.6) 1.90 (1.5-2.4) lr0.60 (0.5-0.7) 0.40 (0.3-0.5) 0.55 (0.5-0.6) 0.13 (0.09-0.2) ppv: positive predictive value, npv: negative predictive value, lr+: positive likelihood ratio, lr-: negative likelihood ration copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com zohrevandi et al 98 12. kothari ru, pancioli a, liu t, brott t, broderick j. cincinnati prehospital stroke scale: reproducibility and validity. ann emerg med.33(4):373-8. 13. frendl dm, strauss dg, underhill bk, goldstein lb. lack of impact of paramedic training and use of the cincinnati prehospital stroke scale on stroke patient identification and on-scene time. stroke. 2009;40(3):754-6. 14. donner a, shoukri mm, klar n, bartfay e. testing the equality of two dependent kappa statistics. stat med. 2000;19(3):373-87. 15. mingfeng h, zhixin w, qihong g, lianda l, yanbin y, jinfang f. validation of the use of the rosier scale in prehospital assessment of stroke. ann indian acad neurol. 2012;15(3):191-5. emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 101 emergency (2014); 2 (2): 101-103 case report transient unexplained shock in 30-year-old trauma patient farzad rahmani1, hanieh ebrahimi bakhtavar1*, kavous shahsavari nia2, neda mohammadi3 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. road traffic injury research center, tabriz university of medical sciences, tabriz, iran 3. department of emergency medicine, urmia university of medical sciences, urmia, iran abstract shock as an inadequate tissue perfusion is one of the frequent causes of death in trauma patients. in this context, there are various reasons for hemodynamic instability and shock including hypovolemic (hemorrhagic), obstructive (cardiac tamponade, tension pneumothorax), cardiogenic, neurogenic, and rarely septic. in the present report, a 30-year-old trauma patient with full clinical signs and symptoms of shock referred while had unknown origin; it was finally recognized as anaphylactic shock. key words: anaphylaxis; shock; insect bites and stings; trauma cite this article as: rahmani f, ebrahimi bakhtavar h, shahsavari nia k, mohammadi n. transient unexplained shock in 30year-old trauma patient. emergency. 2014;2(2):101-3. introduction:1 hock as an inadequate tissue perfusion is one of the frequent causes of death in trauma patients. there are various reasons in this context including hypovolemic (hemorrhagic), obstructive (cardiac tamponade, tension pneumothorax), cardiogenic, neurogenic, and rarely septic shock (1). there are several diagnostic tools available for classification and exploring the origin of the shock. nowadays, rapid ultrasound in shock (rush) examination helps practitioners in decision making regarding the source of shock and consequently proper management (2). in addition, evidences of spinal cord injury, head injury, and pelvic and long bone fractures on imaging are other adjunctive sources. in the present report, a 30-year-old trauma patient with full clinical signs and symptoms of shock referred while had unknown origin. case report: a 30-year-old male, referred to the emergency department, complaining of respiratory distress and hemodynamic instability followed falling from motorcycle. on arrival, patient history was taken from the witnesses at the accident scene who accompanied the patient. during motorcycle deriving, the patient had suddenly lost his control and hit the roadside guard. in initial evaluation, his vital signs were as follows: blood pressure: 80/40 mmhg, pulse rate: 143/minute, rr: 26/ minute and oxygen saturation of 66%. in physical examination, the patient was agitated, he had respiratory distress and lung sounds were symmetric on both sides; slight *corresponding author: hanieh ebrahimi bakhtavar, md. emergency medicine department, tabriz university of medical sciences, tabriz, iran. postal code: 5166614756 fax number:00984113352078 email: hanie_60@yahoo.com received: 9 february 2014; accepted: 21 march 2014 expiratory wheezing was heard in lung auscultation and lung sounds were not reduced. the pupils were isochoric and responded to light and periorbital edema was seen around both eyes. all extremities did not have any deformities and had normal motion. no remarkable issue was found in the spine and the sphincter had normal tone in digital rectal examination. two intravenous lines (gauges 14 and 16) were inserted and two liters crystalloid fluid was infused within 20 minutes. the results of patient’s initial arterial blood gas (abg) were as follows: ph: 7.12, hco3:17.2 meq/liter, paco2: 54.3 mmhg, and pao2: 70 mmhg. because of instability in his hemodynamic status, he was intubated through rapid sequence intubation (rsi) method. chest, hip, and spine anteroposterior and lateral radiographs, extended focused assessment with sonography for trauma (efast), and computed tomography (ct) scan of the brain and cervical spine were performed. while slight edema was seen in brain ct, the other imaging had not any positive findings. about eight hours later, the patient’s level of conscious increased and clinical status improved. he was gradually weaned from mechanical ventilation and extubated. vital signs after extubation were as follows: blood pressure: 130/80 mmhg, pulse rate: 80/minute, respiratory rate: 14/minute, oxygen saturation 97% (in room air). after he was able to speak properly, described the event in details; when he was driving the motorcycle, something like an insect abruptly hit his face and he felt an intense burning in the upper of left eye. he became lethargic and could not remember what happened after. the bite site on patient’s face was carefully examined and a small dot noticed. based on above-mentioned, anaphylactic reaction was recognized. s mailto:hanie_60@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com rahmani et al 102 discussion: in the introduced case, we initially suspected to hemorrhagic shock caused by trauma but despite of using all diagnostic tools the reason of shock remained unknown. after taking the necessary measures and monitoring the patient, his clinical status improved gradually. when he was extubated and gave a detailed history of what happened, the mystery was solved. anaphylaxis is a life-threatening systemic allergic reaction that requires early diagnosis and treatment. in some studies, the prevalence rate of this shock has been reported more than 2% (3). it may be arises from variety of foods, medications, or insect bites (4, 5); it begins following adhesion of allergens to the mast cells membrane bound immunoglobulin e (ige). this results in activation of mast cells and release of various inflammatory mediators and histamine which mediate clinical manifestations of anaphylaxis from hives and localized rash to severe anaphylactic shock with symptoms such as respiratory distress, hypotension, dermal manifestations of localized erythema, urticaria, angioedema, and nausea and vomiting (6). physicians are faced with some significant challenges in diagnosis of anaphylaxis. first, despite numerous definitions of anaphylaxis, there are no reliable diagnostic criteria accepted by all international societies. second, anaphylaxis may appear with numerous atypical manifestations. furthermore, the patients may deny any contact with any stimulus. finally, there is no reliable and acceptable emergency diagnostic testing to rule out or diagnose anaphylaxis (7). despite such challenges in diagnosis, we applied the canadian pediatric surveillance program among several definitions. it defined the anaphylaxis as a “severe allergic reaction to any kind of stimulus with sudden onset lasting less than 24 hours and affecting one or more body systems. it will also produce one or more symptoms such as: hives, itching, flushing, angioedema, stridor, dyspnea, vomiting, diarrhea, and shock” (8). rare manifestations of this disease may be appeared as bradycardia and/or myocardial infarction (9, 10). considering these challenges, diagnosis and treatment of anaphylaxis could be delayed (11). because any delay in diagnosis or incomplete treatment may lead to patient death, emergency physicians should be able to recognize anaphylaxis clinical manifestations and treat it accurately (12). risk factors associated with mortality in these patients include asthma, cardiopulmonary disease, delay or failure to administer adrenaline, and patient’s age. the mortality rate of anaphylactic shock caused by foods (such as peanut) is high among younger ages (adolescence and youth), while in older ages (adult and older adult), the mortality rate of anaphylaxis following insect or animal toxins is high. anaphylactic patients are treated by crystalloid intravenous fluids, corticosteroids, blockers of histamine receptors 1 and 2, and epinephrine, followed by checking and ensuring from the airway and breathing. glucagon can be used for treatment of refractory cases such as resistant hypotension. bronchospasm can be treated by albuterol, ipratropium bromide, and magnesium sulfate (13). after discharging, the patient should be trained in prevention of future contacts, medications use, and use of auto injector device, if it happens again (6). an effective prophylactic method for patients with a positive history of severe allergic reaction to the hymenopterans bites is cluster protocol. this protocol is introduced as a safe and effective treatment modality for immunotherapy of these patients. in this method in defined intervals, an escalating dose of insect venom is injected to patients (14-16). conclusion: for a rapid diagnosis, early treatment and increase survival of patients, anaphylactic shock should be always considered as a differential diagnosis of shock even in a trauma patient. acknowledgment: we acknowledge all staffs of emergency department of imam reza hospital, tabriz, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. atls subcommittee, american college of surgeons’ committee on trauma, international atls working group. advanced trauma life support (atls(r)): the ninth edition. j trauma acute care surg. 2013;74(5):1363-6. 2. perera p, mailhot t, riley d, mandavia d. the rush exam: rapid ultrasound in shock in the evaluation of the critically lll. emerg med clin north am. 2010;28(1):29-56. 3. jacobsen rc, gratton mc. a case of unrecognized prehospital anaphylactic shock. prehosp emerg care. 2011;15(1):61-6. 4. rahmani f, khojasteh smb, bakhtavr he, rahmani f, nia ks, faridaalaee g. poisonous spiders: bites, symptoms, and treatment; an educational review. emergency. 2014;2(2). [in press]. 5. manouchehrifar m, khosravi s, khavanin a, derakhshandeh n. report of 267 cases of scorpion bite referring to an emergency department during one year. emergency. 2013;1(1):24-6. 6. marx ja, hockberger rs, walls rm, adams ga. rosen's emergency medicine: concepts and clinical practice. 8 ed. unided state: elsevier saunders; 2013. p. 1511-28. 7. wang j, sicherer sh, nowak-wegrzyn a. primary care physicians' approach to food-induced anaphylaxis: a survey. j allergy clin immunol. 2004;114(3):689-91. 8. estelle f, simons r, chad z, gold m. real-time reporting of anaphylaxis in infants, children and adolescents by physicians involved in the canadian pediatric surveillance program. j allergy clin immunol. 2002;109(1):s181. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 103 emergency (2014); 2 (2): 101-103 9. alihodzić h, ilić b, mladina n, mrsić d. acute coronary syndrome after hornet bite, type ii kounis syndrome-a case report. lijec vjesn. 2012;135(3-4):82-5. [croatian]. 10. tsai s-h, tzeng b-h. bradycardia in a patient with anaphylactic shock case report. arch intern med. 2005;16(2):91-4. 11. calderón e, méndez j, nazario s. anaphylaxis diagnosis and treatment at an emergency department in puerto rico. p r health sci j. 2013;32(4):170-4. 12. hocagil h, karakilic e, hocagil c, senlikci h, buyukcam f. underdiagnosis of anaphylaxis in the emergency department: misdiagnosed or miscoded? hong kong med j. 2013;19(5):429-33. 13. steele r t. the management of anaphylaxis in primary care. best prac j. 2008;18:10-9. 14. bemanian mh, farhoudi a, pourpak z, et al. systemic and local reactions of bee venom immunotherapy in iran. iran j allergy asthma immunol. 2007;6(4):203-6. 15. catalá m, gómez a, ollo b, gurpegui m, talens m. safety of hymenopteran venoms immunotherapy in a cluster schedule. a nursing perspective. an sist sanit navar. 2008;32(3):409-12. [spanish]. 16. golden db. insect sting anaphylaxis. immunol allergy clin north am. 2007;27(2):261-72. archives of academic emergency medicine. 2019; 7 (1): e37 or i g i n a l re s e a rc h pro-calcitonin, erythrocyte sedimentation rate and c reactive protein in predicting diabetic foot ulcer characteristics; a cross sectional study fahimeh hadavand1, atefeh amouzegar2, hessam amid1∗ 1. infectious diseases and tropical medicine research center, shahid beheshti university of medical sciences, tehran, iran. 2. department of nephrology, firoozgar clinical research development center (fcrdc), iran university of medical sciences, tehran, iran. received: february 2019; accepted: june 2019; published online: 10 july 2019 abstract: introduction: considering the importance of early diagnosis of diabetic foot ulcers and its complications, this study aimed to evaluate the accuracy of erythrocyte sedimentation rate (esr), c reactive protein (crp), and pro-calcitonin (pct) in predicting the ulcer class, osteomyelitis, and peripheral arterial disease (pad). methods: this cross-sectional study was performed on 200 consecutive patients suffering from diabetic foot ulcer who were referred to infectious disease ward. the levels of pct, esr, and crp were measured for all patients and the screening performance characteristics of each marker in predicting the ulcer class, osteomyelitis, and pad was calculated. results: the levels of pct, esr and crp were significantly higher in patients with class iv foot ulcer compared to those with class iii ulcers (p<0.001). patients with evidence of osteomyelitis had significantly higher level of pct, esr and crp. the best cutoff points of pct, esr and crp in predicting osteomyelitis were 0.35 ng/ml (86.1% sensitivity, 45.3% specificity), 56.5 mm/hours (95.8% sensitivity, and 50.0% specificity) and 44 mg/ml (90.3% sensitivity, 57.0% specificity), respectively. the presence of pad was significantly associated with increased levels of the three biomarkers. the best cutoff values for pct, esr and crp in predicting pad were 0.45 (70.8% sensitivity, 71.7% specificity), 61.5 (83.3% sensitivity, 52.0% specificity) and 49 (83.3% sensitivity, 63.8% specificity), respectively. conclusion: based on the findings of the present study, although the accuracy of pct, esr, and crp in predicting the severity of diabetic foot ulcers was fair, increase in the three parameters can predict the occurrence of osteomyelitis and pad following diabetic food development with good accuracy and acceptable sensitivity. keywords: blood sedimentation; procalcitonin; diabetic foot; peripheral arterial disease cite this article as: hadavand f, amouzegar a, amid h. pro-calcitonin, erythrocyte sedimentation rate and c reactive protein in predicting diabetic foot ulcer characteristics; a cross sectional study. arch acad emerg med. 2019; 7(1): e37. 1. introduction diabetes and its complications have affected a large number of people around the world, with an estimated increased worldwide prevalence in all age groups from 2.8% in 2000 to 4.4% in 2030 (1). despite the medical and surgical advances in the last decade, problems with diabetic foot, which is one of the most important chronic complications of diabetes, remain a health problem and is the most important cause of non-traumatic foot injuries (2). the likelihood of a ∗corresponding author: hessam amid; infectious diseases and tropical medicine research center, shahid beheshti university of medical sciences, 7th floor, tehran, iran. postal code: 1985717443 email: drhesamamid66@yahoo.com tel: 00982122672493 diabetic patient developing foot lesions (ulcer / gangrene) is estimated to be 15-25 percent throughout life, with an annual incidence of 1 to 4.1 percent, more than 15 percent of which ultimately results in amputation of the organ. some risk factors of diabetic foot ulcers are as follow: having had diabetes for over 10 years, male gender, uncontrolled blood sugar, and cardiovascular, renal and ocular diseases (2). another important issue in patients with diabetic foot ulcers is the high susceptibility of these ulcers to severe inflammation and wound infections. patients with diabetes mellitus are prone to severe foot infection due to neuropathy and vascular dysfunction (3). it is difficult to determine severity of diabetic foot ulcer and to distinguish non-infectious and infectious wounds in the early stages (4). when clinical symptoms are misleading, labthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. hadavand et al. 2 oratory tests can help determine disease severity and also diagnose the foot ulcer infection. many studies have focused on the role of inflammatory markers such as erythrocyte sedimentation rate (esr) and c reactive protein (crp), as well as pro-calcitonin (pct) to predict the onset of inflammation and infection, especially in bacterial involvement of diabetic wounds (5-8). in addition, the diagnostic and predictive values of some circulating inflammatory parameters such as leukocyte counts and circulating inflammatory proteins are evaluated (9, 10). pct is a protein precursor of calcitonin hormone, which is synthesized and secreted by the c-cells in the thyroid gland. pct production has been proven to occur after activation of inflammatory cascade by the liver and mononuclear cells and is modulated through cytokines associated with sepsis (11). pct has also been shown to play a major role in diagnosis of diabetic foot ulcers, and its role can be even more important than crp (12-14). based on above-mentioned points, this study aimed to evaluate the value of pct, esr, and crp in predicting the ulcer class, as well as presence or absence of osteomyelitis and peripheral arterial disease (pad). 2. methods 2.1. study design and setting this cross-sectional study was performed on 200 consecutive patients suffering from diabetic foot ulcer who were referred to infectious disease ward of imam hussein hospital, tehran, iran, from january 2017 to september 2018. the levels of pct esr, and crp were measured for all patients and the screening performance characteristics of each marker in predicting the ulcer class, osteomyelitis, and pad was calculated. informed consent was obtained from each patient and the study protocol as approved by the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.msp.rec.1396.844) 2.2. participants adult (age > 18 years) diabetic patients with foot infection, who were hospitalized in the mentioned hospital were included. patients with septic shock, unstable hemodynamics or without consent to participate in the study were excluded. 2.3. data gathering the baseline characteristics including demographics, medical history, comorbidities, duration of diabetes, and the presence of underlying immunodeficiency or using immunosuppressive medication were collected by reviewing the patients’ profiles. baseline levels of laboratory biomarkers were also measured and documented for all patients at the time of admission to infectious disease ward. serum pct was measured using an enzyme-linked fluorescence assay and its concentration was measured using routine immunoassay (brahms pct kryptor system, brahms, hennigsdorf, germany). crp concentration was measured with routine immunoassay (bionic, america). the sensitivity of the assay and the target value of the calibrator have been standardized against the reference material erm-da 472/ifcc. esr was measured using a closed automated method, using a highly sensitive assay. an infectious disease resident was responsible for data gathering. 2.4. definitions the severity of diabetic foot was classified according to the perfusion, extent, depth, infection, sensation (pedis) classification system (15). based on this classification diabetic ulcers are classified as uninfected (grade 1), mild (grade 2), moderate (grade 3), and severe (grade 4). mild ulcers: presence of >2 manifestations of inflammation (purulence, pain, warmth) moderate ulcers: cellulitis extending >2 cm and involvement of muscle, tendon, joint severe ulcers: infection with systemic toxicity (fever, tachycardia, hypotension, etc.) osteomyelitis was diagnosed using magnetic resonance imaging (mri) findings. diabetic foot ulcers were diagnosed based on the clinical manifestation. pad was verified based on the ankle brachial index (abi < 1.2). 2.5. statistical analysis descriptive analysis was used to describe the data, including mean ± standard deviation (sd) for quantitative variables and frequency (percentage) for categorical variables. chi square test, independent t test and mann-whitney u test were used for comparison of variables. the correlation between quantitative variables was tested by the pearson’s correlation test. the receiver operating characteristic (roc) curve analysis was used to assess the value of biomarkers in predicting the studied endpoints. for statistical analysis, the statistical software ibm spss statistics for windows version 22.0 (ibm corp. released 2013, armonk, new york) was used. p values <0.05 were considered statistically significant. 3. results 3.1. baseline characteristics of studied patients 200 patients with the mean age of 61.26 ± 11.32 (33 -87) years were included (71.5% male). according to the pedis classithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e37 figure 1: area under the receiver operating characteristic (roc) curve of pro-calcitonin (pct), erythrocyte sedimentation rate (esr), and c reactive protein (crp) in predicting the ulcer class, osteomyelitis, and peripheral arterial disease (pad). table 1: mean pro-calcitonin (pct), erythrocyte sedimentation rate (esr), and c reactive protein (crp) measures based on ulcer class and presence or absence of osteomyelitis and peripheral arterial disease (pad) index pct p crp p esr p ulcer class iii 0.39 ± 0.17 <0.001 43.84 ± 24.01 <0.001 59.30 ± 19.81 <0.001 iv 0.63 ± 0.59 56.96 ±30.22 73.00 ± 21.79 osteomyelitis absent 0.38 ± 0.17 <0.001 39.35 ± 17.87 <0.001 55.73 ± 15.54 <0.001 present 0.77 ± 0.69 71.86 ± 31.42 86.57 ± 17.41 pad absent 0.47 ± 0.48 <0.001 43.68 ± 20.10 <0.001 61.36 ± 19.36 <0.001 present 0.69 ± 0.39 74.40 ± 36.93 84.17 ± 20.86 data are presented as mean ± standard deviation. fication, 45.0% were class iii and 55.0% had class iv of diabetic foot ulcer. the mean duration of suffering from diabetes was 11.79 ± 3.94 years. 13.0% were immune-deficient all of whom used immunosuppressive medications. according to the mri findings, the evidence of osteomyelitis was found in 36.0%. mean hemoglobin a1c was 7.91 ± 1.81% ad it ranged from 4.7 to 18.3. mean abi was 1.02 ± 0.22 and 24.0% suffered from pad with abi less than 0.9. regarding laboratory parameters, mean crp was 51.05 ± 28.30 mg/ml, mean pct was 0.52 ± 0.47 ng/ml and mean esr was 66.84 ± 21.96 mm/hr. there was a significant correlation between pct and esr (r = 0.395, p < 0.001) as well as pct and crp (r = 0.334, p < 0.001). 3.2. prediction of ulcer class the level of pct, esr and crp were significantly higher in patients with class iv foot ulcer compared to those with class iii (p<0.001, table 1). as summarized in table 2 and figure 1, esr, crp and pct had moderate value for predicting class of diabetic foot ulcer according to roc analysis. 3.3. prediction of osteomyelitis patients with the evidence of osteomyelitis had significantly higher levels of pct, esr and crp (table 1). the areas under the roc curve of pct, esr and crp in predicting osteomyelitis were 0.787, 0.869, and 0.907, respectively; showing high predictive value for each biomarker (table 2, figure 1). the best cutoff points and yielded sensitivity and sensitivity of pct, esr and crp at that points in predicting osteomyelitis were 0.35 ng/ml (sensitivity of 86.1% and specificity of 45.3%), 56.5 mm/hours (sensitivity of 95.8% and specificity of 50.0%) and 44 mg/ml (sensitivity of 90.3% and specificity of 57.0%), respectively. 3.4. prediction of pad the presence of pad was significantly associated with increased levels of the three biomarkers. the areas under the roc curve of pct, esr and crp in predicting pad were 0.733, 0.807 and 0.789, respectively (table 2, figure 1). the best cutthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. hadavand et al. 4 table 2: screening performance characteristics of pro-calcitonin (pct), erythrocyte sedimentation rate (esr), and c reactive protein (crp) in predicting ulcer class, osteomyelitis, and peripheral arterial disease (pad) index auc sensitivity specificity ppv npv ulcer class pct 0.68 (0.60-0.75) 74.54(66.28-82.72) 55.65(51.26-59.89) 67.2 64.1 crp 0.64 (0.56-0.72) 65.57(61.04-69.73) 46.78(41.75-51.83) 60.0 52.5 esr 0.66 (0.59-0.74) 63.68(60.76-66.57) 52.28(44.65-59.83) 62.0 54.0 osteomyelitis pct 0.79 (0.72-0.85) 86.17(75.46-94.71) 45.37(39.94-50.73) 47.0 85.3 crp 0.91 (0.86-0.95) 90.38(80.41-97.27) 57.04(49.08-68.46) 54.1 91.3 esr 0.87 (0.82-0.92) 95.82(93.89-97.73) 50.08(42.32-57.86) 51.9 95.9 pad pct 0.73(0.64-0.82) 70.88(65.95-76.93) 71.76(69.19-74.17) 44.1 88.6 crp 0.79(0.71-0.87) 83.36(78.81-87.89) 63.89(58.26-68.13) 42.1 92.4 esr 0.81(0.73-0.88) 83.32(78.54-87.99) 52.08(47.82-57.19) 35.4 90.8 data are calculated in cutoffs of 0.35 for pct, 44.0 for crp, and 61.5 for esr. all data are presented with 95% confidence interval. ppv: positive predictive value; npv: negative predictive value; auc: area under the roc curve. off values for pct, esr and crp in predicting pad were 0.45 (sensitivity of 70.8% and specificity of 71.7%), 61.5 (sensitivity of 83.3% and specificity of 52.0%) and 49 (sensitivity of 83.3% and specificity of 63.8%), respectively. 4. discussion based on the findings of the present study, although the accuracy of pct, esr and crp in predicting the severity of diabetic foot ulcers was fair, the increase of the three parameters could predict the occurrence of osteomyelitis and pad following diabetic food development with good accuracy and acceptable sensitivity. these three indicators seem to be beneficial in predicting wound infections rather than wound healing or classification. in the study by korkmaz et al., the amount of crp and esr in patients with infectious ulcers was significantly higher than that of patients with non-infectious diabetic ulcers. based on the analysis of the roc curve, crp had the highest capability for detecting infection, and the best cut-off point for crp in predicting diabetic wound infection was 28 (15). this cut point, however, was 44 in our study for assessing the severity of the wound itself. in the study by park et al., pct and crp showed a high correlation with severity of diabetic ulcer infection, which was not consistent with our study. also, pct levels could be used to differentiate the existence of infection (16). this inconsistency can be due to the different methodology of our study as we were aiming to evaluate the general severity of wound, independent of infection, but in the park et al. study, they have concentrated on the severity of wound infection rather than overall severity. in the study by massara et al., exploring the relationship between these markers and the onset of diabetic foot ulcer, showed that pct and crp markers had the highest diagnostic values for predicting the incidence of diabetic foot ulcers (13). in the study by victoria et al., the sensitivity and specificity of pct in prediction of diabetic foot ulcer infection were 81% and 90%, respectively. however, other markers were not associated with diabetic foot ulcer infection (17). in the study by jonaidi et al. the best cutoff point, sensitivity and specificity for crp and pct to distinguish infection in 30 patients were reported as 7.1 mg/dl, 80%, 74%, and 0.21, 70% and 74%, respectively (18). a possible explanation for the visible differences between their study and ours could be the limited number of individuals in our study population, affecting the power of the results. several studies have been conducted on the relationship of increase in esr and crp with predicting osteomyelitis in diabetic patients (19-21), but few studies have been done on the role of pct in predicting osteomyelitis. only in the study by redman et al., the prominent role of pct in periodontitis has been shown, which was shown to be even more potent than crp (22). also, there are few studies on the role of these markers in prediction of pad occurrence. increase in esr and crp was also associated with an increased risk of pad occurrence (23). in general, due to the confirmation of the role of pct, esr and crp indicators in predicting the occurrence of osteomyelitis and pad complications following diabetic foot infection, the three indicators can be used to design and introduce scoring systems that determine the severity or development of related complications of diabetic foot ulcer. 5. limitation small sample size and unknown duration of ulcers and infections were among the limitations of the present study. all patients were hospitalized, so the ulcers were in pedis 3 and 4 stages. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e37 6. conclusion although the role of pct, esr and crp indices was not significant in predicting the severity of diabetic foot ulcer, the increase of the three parameters can predict the occurrence of two complications of osteomyelitis and pad following the progression of diabetes with good accuracy and high sensitivity. 7. appendix 7.1. acknowledgements this article is extracted from the residency thesis of hessam amid in infectious diseases and tropical medicine program at shahid beheshti university of medical science, tehran, iran. 7.2. author contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors orcids fahimeh hadavand: 0000-0002-6565-1344 atefeh amouzegar: 0000-0003-3090-1662 hessam amid: 0000-0001-8552-154x 7.3. funding/support none. 7.4. conflict of interest the authors have no conflict of interest. references 1. wild s, roglic g, green a, sicree r, king h. global prevalence of diabetes: estimates for the year 2000 and projections for 2030. diabetes care. 2004;27(5):1047-53. 2. kalish j, hamdan a. management of diabetic foot problems. journal of vascular surgery. 2010;51(2):476-86. 3. hosseini r, rasouli a, baradaran h. diabetic foot risk factors in patients with diabetes at the kamkar hospital diabetes clinic in qom, iran 2008;25(4):21-6. 4. yesil s, akinci b, yener s, bayraktar f, karabay o, havitcioglu h, et al. predictors of amputation in diabetics with foot ulcer: single center experience in a large turkish cohort. hormones. 2009;8(4):286-95. 5. simon l, gauvin f, amre dk, saint-louis p, lacroix j. serum procalcitonin and c-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. clinical infectious diseases. 2004;39(2):206-17. 6. assicot m, bohuon c, gendrel d, raymond j, carsin h, guilbaud j. high serum procalcitonin concentrations in patients with sepsis and infection. the lancet. 1993;341(8844):515-8. 7. hammer s, meisner f, dirschedl p, hobel g, fraunberger p, meiser b, et al. procalcitonin: a new marker for diagnosis of acute rejection and bacterial infection in patients after heart and lung transplantation. transplant immunology. 1998;6(4):235-41. 8. kordek a, podraza w, czajka r. reliability of semiquantitative determination of procalcitonin serum concentrations in neonates. diagnostic microbiology and infectious disease. 2006;56(1):31-4. 9. barati m, eshaghi m, noori n. evaluation of correlation between esr and crp with osteomylitis in diabetic foot. razi journal of medical sciences. 2003;10(33):9-15. 10. armstrong dg, perales ta, murff rt, edelson gw, welchon jg. value of white blood cell count with differential in the acute diabetic foot infection. journal of the american podiatric medical association. 1996;86(5):224-7. 11. jeandrot a, richard j-l, combescure c, jourdan n, finge s, rodier m, et al. serum procalcitonin and c-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study. diabetologia. 2008;51(2):347-52. 12. uzun g, solmazgul e, curuksulu h, turhan v, ardic n, top c, et al. procalcitonin as a diagnostic aid in diabetic foot infections. the tohoku journal of experimental medicine. 2007;213(4):305-12. 13. massara m, de caridi g, serra r, barilla d, cutrupi a, volpe a, et al. the role of procalcitonin as a marker of diabetic foot ulcer infection. international wound journal. 2017;14(1):31-4. 14. chuan f, tang k, jiang p, zhou b, he x. reliability and validity of the perfusion, extent, depth, infection and sensation (pedis) classification system and score in patients with diabetic foot ulcer. plos one. 2015;10(4):e0124739. 15. korkmaz p, kocak h, onbasi k, bicici p, ozmen a, uyar c, et al. the role of serum procalcitonin, interleukin-6, and fibrinogen levels in differential diagnosis of diabetic foot ulcer infection. journal of diabetes research. 2018;20(2). 16. park jh, suh dh, kim hj, lee yi, kwak ih, choi gw. role of procalcitonin in infected diabetic foot ulcer. diabetes research and clinical practice. 2017;128(4):51-7. 17. aura victoria van asten s, joseph geradus peters e, xi y, alfred lavery l. the role of biomarkers to diagnose diabetic foot osteomyelitis. a meta-analysis. current diabetes reviews. 2016;12(4):396-402. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. hadavand et al. 6 18. jafari nj, firouzabadi ms, izadi m, firouzabadi mss, saburi a. can procalcitonin be an accurate diagnostic marker for the classification of diabetic foot ulcers? international journal of endocrinology and metabolism. 2014;12(1). 19. sattar n, hingorani ad. c-reactive protein and prognosis in diabetes: getting to the heart of the matter. diabetes. 2009;58(4):798-9. 20. wolfe f. the c-reactive protein but not erythrocyte sedimentation rate is associated with clinical severity in patients with osteoarthritis of the knee or hip. the journal of rheumatology. 1997;24(8):1486-8. 21. van asten sa, nichols a, la fontaine j, bhavan k, peters ej, lavery la. the value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis. international wound journal. 2017;14(1):40-5. 22. redman r, kerr g, payne jb, mikuls tr, huang j, sayles h, et al. salivary and serum procalcitonin and creactive protein as biomarkers of periodontitis in united states veterans with osteoarthritis or rheumatoid arthritis. biotechnic & histochemistry. 2016;91(2):77-85. 23. garofolo l, ferreira srg, miranda junior f. association between peripheral arterial disease and creactive protein in the japanese-brazilian population. revista do colegio brasileiro de cirurgioes. 2014;41(3):168-75. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7(1); e4 or i g i n a l re s e a rc h continuous education of basic life support (bls) through social media; a quasi-experimental study seyyed mahdi zia ziabari1, vahid monsef kasmaei1, lida khoshgozaran1∗, maryam shakiba2 1. department of emergency medicine, school of medicine, guilan university of medical sciences, rasht, iran. 2. guilan road trauma research center, school of health, guilan university of medical sciences, rasht, iran. received: september 2018; accepted: october 2018; published online: 20 january 2019 abstract: introduction: it is imperative, if not fundamental, for medical students to receive continuing education in basic life support (bls). this present study aimed to investigate the effectiveness of continuing education using social media in this regard. methods: in this quasi-experimental study, a questionnaire containing 20 items about bls awareness was completed by the interns who were trained monthly in the emergency medicine training course. then half of the interns received distant education through telegram software up to three months, and the other did not receive any further education. again, both groups completed the questionnaire at the end of the third month. results: 100 medical interns with the mean age of 25.05 ± 1.26 years were allocated to two groups of 50 subjects (65.0% female). two groups were similar regarding the mean age (p = 0.304), gender (p = 0.529), mean awareness score at the beginning of the study (p = 0.916), and average pre-internship exam score (p = 0.080). the mean awareness score of medical interns increased significantly in intervention (11.44 ± 2.37 to 14.88 ± 1.97, p < 0.0001) and control (11.38 ± 3.22 to 12.54 ± 3.04, p < 0.0001) groups at second examination. but mean difference of awareness score, before and after the education, was significantly higher in intervention group (3.44 ± 1.48 versus 1.16 ± 1.51; p < 0.0001). conclusion: the increase in the bls awareness score was significantly higher in medical interns who were continuously educated using telegram social media software. keywords: education; cardiopulmonary resuscitation; mobile application; computer-assisted instruction cite this article as: zia ziabari sm, monsef kasmaei v, khoshgozaran l, shakiba m. continuous education of basic life support (bls) through social media; a quasi-experimental study. arch acad emerg med. 2019; 7(1): e4. 1. introduction despite many advances in medicine, sudden cardiac arrest remains a leading cause of death in most countries worldwide (1). subsequent outcomes of cardiac arrest depend on basic measures such as chest compression, defibrillator, and more advanced actions (2). the importance of cardiopulmonary resuscitation (cpr) has been well documented, so that a good cpr can reduce mortality up to 50% (3). in general, the ability to diagnose and treat a respiratory or cardiac arrest is a basic medical skill that all health care providers including medical students should have these skills. they should learn to carry out cpr and pre-hospital activities and increase their skills during educational courses (4, 5). the measures for basic life support (bls) for adolescents outside ∗corresponding author: lida khoshgozaran, school of medicine, guilan university of medical sciences, rasht, iran. e-mail: lida.khoshgozaran@gmail.com tel: 00989111414384 the hospital include rapid detection of cardiac arrest, quick activation of the emergency medical services (ems), pulse check, cpr, and rapid defibrillation with an automated external defibrillator (aed) (6). since the quality of cpr depends on the learner memorizing and applying the scientific and practical skills, continuing education should be provided in this regard (7). the use of e-learning in medical education has had good results and has been effective (8, 9). in this way, electronic tools and software are used as a means to improve learning, communication and interactions, and increasingly to train medical professionals (10, 11). the advancement in e-learning technology and the use of computers and online training has made it possible to save costs and transfer data without any time limit. also, the personto-person training capabilities meet the learner’s needs well (12, 13). although the bls course is held every two years, researches have shown that quality of bls clinical skills begin to decrease after 3 months (14-16). studies showed that the students had more tendency and self-confidence to perform cpr after multiple educational sessions (17, 18). researches this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. zia ziabari et al. 2 figure 1: mean awareness score in intervention and control groups before and after the education (p < 0.0001). have also shown that watching an educational video clip on cell phone to remind and review bls content increases the skill and self-confidence to carry out cpr and the use of aed in rescuers (18). considering the above mentioned, we decide to investigate the effectiveness of continuous education of bls through social media (telegram software) on medical interns. 2. methods 2.1. study design and setting this quasi-experimental study, was conducted on medical interns who were trained monthly in the emergency medicine training course of poursina hospital, rasht, iran, from august 2016 to july 2017. all medical interns entered the study with informed consent, and reviewing the research project was carried out by the ethics committee of the research unit of guilan university of medical sciences (ir. gums.rec.1396.69). the study was registered in iranian registry of clinical trials with number: irct20110818007369n5. 2.2. participants all medical interns who were passed the one month emergency medicine educational program in mentioned hospital during the study period were enrolled. dissatisfaction with continuing to participate in the study, lack of access to smartphone, not using of telegram software were among the exclusion criteria. there was no any sex or age limitation. the medical interns were given an ethical commitment that their personal information would remain confidential and they also gave a moral commitment to not share the contents of the classroom and the software until the end of the study with other interns. 2.3. data gathering to assess the students’ awareness regarding the bls at the beginning and end of the study, a questionnaire containing 20 items was used (19). the persian version of this questionnaire was translated into english, and it was again translated into persian by a native. to determine the quantitative validity, content validity ratio (cvr) and content validity index (cvi) were used. the score for cut-off point in lawshe table for 10 experts was 0.62. in the questionnaire, the cvr scores of all questions were 0.8 to 1, which is confirmed in terms of cvr index. also, in terms of the cvi, the lowest cvi was 0.7 and its maximum was 1 in the three dimensions of relevance, simplicity and clarity. therefore, questions with a cvi of between 0.7 and 0.8 were subject to partial review, and the remaining questions due to the high cvi remained unchanged. to determine the internal consistency of the questions, the richardson coefficient 20 was used, with the obtained alpha value equal to 0.996 (more than 0.7), indicating the internal consistency of the questions in the calculation of students’ awareness to the bls algorithm. 2.4. intervention mentioned questionnaire was first distributed among medical interns, and they were asked to answer the questions based on their information and to enter data including their name, age, gender, and average pre-internship exam score in the questionnaire. based on the answers to the questions, a score of 1-20 was attributed to the students (correct answer to each question had 1 score, the wrong answer was zero, and negative score did not belong to the wrong answers). the scores obtained from the questionnaire were gained with algebraic scores from each question (zero or one), and the students’ awareness was measured based on these scores. after completing the questionnaire, all of the interns received an in-person tutorial using powerpoint software by the teachers of rasht poursina hospital, and an emergency medicine resident, based on the 2015 aha educational guideline on bls for adults and children (1, 6, 20-22). after being trained at the hospital, half of the interns who were selected sequentially and non-randomly, received distant continuing education for up to three months through social media (telegram software, which is comprehensive and accessible in iran). this training was conducted in a person-to-person manner by sending abstracts of taught materials in the classroom based on the 2015 aha guidelines, which was presented in short texts, photographs and educational videos related to how to perform bls. the other half of the participants did not receive any further training after the in-person education offered at the hospital. then, at the end of the third month after holding the first in-person class, both groups received the questionnaire through the telegram software, and the awareness on bls was measured by refilling the same questionnaire. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7(1); e4 table 1: basel line characteristics of case (continuous education with social media) and control (regular education) groups variable value p values gender (male/female ratio) case 31/19 (1.63) 0.529 control 34/16(2.12) age (year) case 24.92 ± 1.01 0.304 control 25.18 ± 1.46 awareness score case 11.44 ± 2.37 0.916 control 11.38 ± 3.22 pre-internship exam score case 15.97 ± 0.81 0.080 control 16.24 ± 0.71 data are presented as mean ± standard deviation. 2.5. statistical analysis we calculated sample size using altman monogram with α: 0.01, β: 0.2 and d2: 0.9. the allocation ratio was 1:1, and finally 50 students entered in each group. data were analysed using mean and standard deviation. normality of data was evaluated using skewness and kurtosis indices. paired ttest and independent t-test were used to compare means between the groups. all analyses were performed in spss version 19 and a significant level was considered as below 0.05. 3. results 119 medical interns were studied. 19 out of 119 students were excluded (3 were not using the telegram software, 4 were not satisfied to participate to the study, 12 did not fill the questionnaire after 3 months). finally 100 medical interns with the mean age of 25.05 ± 1.26 (23 31) years were allocated to two groups of 50 subjects (65.0% female). table 1 compare the baseline characteristics of two groups. two groups were similar regarding the mean age (p = 0.304), gender (p = 0.529), mean awareness score at the beginning of the study (p = 0.916), and average pre-internship exam score (p = 0.080). the mean awareness score of medical interns increased significantly in intervention (11.44 ± 2.37 to 14.88 ± 1.97, p < 0.0001) and control (11.38 ± 3.22 to 12.54 ± 3.04, p < 0.0001) groups at second examination (figure 1). but mean difference of awareness score, before and after the education, was significantly higher in intervention group (3.44 ± 1.48 versus 1.16 ± 1.51; p < 0.0001). 4. discussion the findings of this study showed that the increase in the bls awareness score was significantly higher in medical interns who were continuously educated using telegram social media software. an interventional study by khorasani et al. showed that the mean score of awareness and practice before and after the primary emergency care education workshops indicated a significant difference in practice before and after taking part in workshop in dentistry interns (23). ji yun ahn et al. showed that watching an educational video clip in cell phone in order to remind and review the bls materials increased skill and self-confidence to perform cpr and using aed in rescuers after three months (18). in our study, the impact of this continuous education was seen positively, although there was no need to use a memory card and a reminder message to view clips and educational pictures, and all interns could have enough time to read, understand, and answer person-to-person questions using telegram software within three months. in a randomized controlled trial, eric l. einspruch et al. in the united states, compared memorizing cpr skills in conventional education to teaching through 22-minute self-learning videos. in both groups, the decrease amount in skills after two months was generally the same. in the second assessment two months later, the subjects of the self-learning group were better than the conventional group in all skills, except for the emergency call, which were the same for both groups. in the assessment with manikin, the self-learning group was better than the conventional training group in the ventilation volume, but both groups performed equally in proper hand positioning in chest compression and massage depth (7). contrary to this study showing a decrease in skills after two months, the awareness of interns’ after three-month continuing education did not reduce, but increased significantly compared to the control group in our study. in general, the ability to diagnose and treat a respiratory or cardiac arrest is a basic medical skill that all medical students should have the skills. they should learn cpr and pre-hospital activities and increase their skills during educational courses (4, 5). given that these skills and awareness about how to conduct appropriate bls are forgotten over time, and according to aha 2015, studies have demonstrated that deterioration of bls skills in as little as 3 months after initial training (14-16), therefore, it should be emphasized that in order to maintain and improve clinical skills, they need to be adequately memorized with repeated training (7). with the help of information and communication technology capabilities, students are able to provide information at any time and place quickly. the learner can have enough time to read, understand, and answer the questions in a person to person manner, in spite of his/her work, family, disability and geographical location; this encourages and motivates him/her (24). considering the widespread use of modern telegram software in society especially in the student population, this study examined the effect of person to person and continuing education of cpr operation using telegram among medical students. since all students were spending their internship in different parts, the software prothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sm. zia ziabari et al. 4 vided continuous communication with each other. 5. limitation the weaknesses of this study were the lack of randomization and the impossibility of blinding due to the nature of the study, and the lack of facilities for examining the practical skills of students at the same time. since it is not possible to examine skills in addition to knowledge, it is suggested that future studies consider these two issues together. 6. conclusion the results of this study indicate the positive effect of continuing education of bls through telegram software on the awareness of medical students. this finding can demonstrate the positive role of using modern communication networks and the possibility of using them in the student community. 7. appendix 7.1. acknowledgements this research was supported by guilan road trauma research center. we thank our colleagues from rasht poursina hospital who provided insight and expertise that greatly assisted the research. 7.2. authors’ contribution seyyed mahdi zia ziabari devised the study, the main conceptual ideas and proof outline. lida khoshgozaran worked out almost all of the technical details. maryam shakiba performed analysis and interpretation of the data and vahid monsef kasmaei took the lead in charge of overall direction and planning. all authors discussed the results and commented on the manuscript. 7.3. funding/support none. 7.4. conflict of interest we know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. as corresponding author, i confirm that the manuscript has been read and approved for submission by all the named authors. references 1. travers ah rt, bobrow bj, et al. . cpr overview: american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 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http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e43 or i g i n a l re s e a rc h laboratory parameters in detection of covid-19 patients with positive rt-pcr; a diagnostic accuracy study rajab mardani1, abbas ahmadi vasmehjani2, fatemeh zali3, alireza gholami4, seyed dawood mousavi nasab5∗, hooman kaghazian5, mehdi kaviani6, nayebali ahmadi7 † 1. department of biochemistry, pasteur institute of iran, tehran, iran. 2. department of virology, school of public health, tehran university of medical sciences, tehran, iran. 3. department of clinical biochemistry, faculty of medicine, tehran university of medical science, tehran, iran. 4. who collaborating center for reference and research on rabies, pasteur institute of iran, tehran, iran. 5. department of research and development, production and research complex, pasteur institute of iran, tehran, iran. 6. expert of shohada-e yaft abad hospital, iran university of medical sciences, tehran, iran. 7. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. received: february 2020; accepted: march 2020; published online: 4 april 2020 abstract: introduction: the role of laboratory parameters in screening of covid-19 cases has not been definitely established. this study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive rt-pcr for covid-19. methods: this diagnostic accuracy study was conducted on suspected covid-19 patients, who presented to behpooyan clinic medical center in tehran (iran) from 22 february to 14 march, 2020. patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (rt-pcr) for covid-19, and the accuracy of different laboratory parameters in predicting cases with positive rt-pcr was evaluated using area under the roc curve (auc). results: two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). the result of rt-pcr for covid-19 was positive in 70 (35%) cases. patients with positive rt-pcr had significantly higher neutrophil (neu) count (p = 0.0001), and c-reactive protein (crp) (p = 0.04), lactate dehydrogenase (ldh) (p = 0.0001), aspartate aminotransferase (ast) (p = 0.001), alanine aminotransferase (alt) (p = 0.0001), and urea (p = 0.001) levels in serum. in addition, patients with positive rt-pcr had lower white blood cell (wbc) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. alt (auc = 0.879), crp (auc = 0.870), neu (auc = 0.858), ldh (auc = 0.835), and urea (auc = 0.835) had very good accuracy in predicting cases with positive rt-pcr for covid-19, respectively. conclusion: our findings suggest that level of ldh, crp, alt and neu can be used to predict the result of covid-19 test. they can help in detection of covid-19 patients. keywords: sars-cov-2; covid-19; biomarkers, biochemistry; blood cell count; reverse transcriptase polymerase chain reaction cite this article as: mardani r, ahmadi vasmehjani a, zali f, gholami a, mousavi nasab s d, kaghazian h, kaviani m, ahmadi n. laboratory parameters in detection of covid-19 patients with positive rt-pcr; a diagnostic accuracy study. arch acad emerg med. 2020; 8(1): e43. ∗corresponding author: seyed dawood mousavi nasab; department of research and development, production and research complex, pasteur institute of iran, tehran, iran. email: d_mousavinasab@pasteur.ac.ir, tel: +98-02636100990 † corresponding author: nayebali ahmadi; proteomics research center, shahid beheshti university of medical sciences, tehran, iran. email address: nayebalia@sbmu.ac.ir, tel: 0098021-22714248 1. introduction compared to 2002/2003 sars-cov and 2012–2014 merscov epidemics, covid-19 coronavirus rapidly spread to other parts of the world (185 countries and territories, last updated: march 21, 2020)(1). in symptomatic patients, the clinical manifestations of the disease usually start after less than a week, consisting of fever (body temperature 37 to 38◦c), cough, nasal congestion, and fatigue (2). pneumonia mostly occurs in the second this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. mardani et al. 2 or third week of a symptomatic infection (3). comparison of hematological parameters between mild and severe cases of covid-19 showed significant differences in interleukin-6 (il-6), d-dimer, glucose (glu), thrombin time (tt), fibrinogen (fib) and c-reactive protein (crp) (4). fan et al. analyzed the hematological indices of covid-19 infected patients between the intensive care unit (icu) and non-icu patients. they showed lymphopenia and raised lactate dehydrogenase (ldh) were associated with higher rate of icu admissions. patients who were transferred to the icu had a lower nadir lymphocyte count, nadir monocyte count and nadir hemoglobin, and higher peak neutrophil (neu) count and peak ldh levels compared to patients who did not require icu stay (5) . many patients with mers-cov had liver function abnormalities with elevated alanine aminotransferase (alt), aspartate aminotransferase (ast), and ldh (6). also laboratory data on sars have shown that most patients had elevated crp levels, lymphopenia, leukopenia, and elevated levels of aminotransferase, ldh and creatine kinase (7). a series of recently published articles have reported the epidemiological and clinical characteristics of patients with covid-19 disease, but data regarding the laboratory characteristics of infected individuals are limited (8-10). this study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive rt-pcr for covid-19. 2. methods 2.1. study design and setting this diagnostic accuracy study was conducted on suspected covid-19 patients, who presented to behpooyan clinic medical center in tehran (iran) from 22 february to 14 march, 2020. patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (rt-pcr) for covid-19 and the accuracy of different laboratory parameters in predicting cases with positive rt-pcr was evaluated using area under the roc curve (auc). the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences (ethical code: ir.sbmu.retech.rec.1399.010). 2.2. participants outpatients with suspected covid-19 having initial respiratory signs (including sore throat without shortness of breath), fever, cough, muscle ache, and headache were included (1). 2.3. data gathering pharyngeal swab samples were collected for covid-19 test on presentation. blood samples were collected from each participant and routine blood test including white blood cell count (wbc), lymphocyte count (lym), and neutrophil count (neu) were performed on the blood samples. furthermore, blood biochemistry parameters such as aspartate aminotransferase (ast), alanine aminotransferase (alt), urea, c-reactive protein (crp), as well as albumin and lactate dehydrogenase (ldh) were assessed using hitachi 7600-020 automated biochemistry analyzer. 2.4. statistical analysis data on urea, wbc, albumin, ast, alt, ldh levels were expressed as mean ± standard deviation (sd). differences in the levels of urea, crp, wbc, lym, neu, albumin, ast, alt and ldh between the rt-pcr positive and negative patients were assessed using student’s t-test. receiver operating characteristic (roc) curve and auc were used to analyze the optimal cut-off for prediction of positive rt-pcr cases. in this study, auc 0.9 to 1 was defined as excellent accuracy, 0.8 to 0.9 as very good, 0.7 to 0.8 as good, 0.6 to 0.7 as sufficient, 0.5 to 0.6 as bad, and < 0.5 as poor (useless test). 3. results 3.1. characteristics of the studied cases two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). 40.2% of cases were in the 30 to 49 years age range. the result of rt-pcr for covid-19 was positive in 70 (35%) cases and negative in 130 (65%). groups of patients with positive and negative rt-pcr were similar regarding gender (p = 0.17) and age (p = 0.35) distribution. 3.2. laboratory parameters table 1 compares the laboratory parameters of patients with positive and negative rt-pcr. patients with positive rt-pcr had significantly higher neu count (p = 0.0001), and crp (p = 0.04), ldh (p = 0.0001), ast (p = 0.001), alt (p = 0.0001), and urea (p = 0.001) levels in serum. in addition, patients with positive rt-pcr had lower wbc count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. table 2 and figure 1 show the area under the roc curve of studied parameters in predicting cases with positive rt-pcr for covid-19. alt (auc = 0.879), crp (auc = 0.870), neu (auc = 0.858), ldh (auc = 0.835), and urea (0.835) had very good accuracy in predicting cases with positive rt-pcr for covid19, respectively. 4. discussion based on the findings of this study alt, crp, neu, ldh, and urea have very good accuracy in predicting cases with positive rt-pcr for covid-19, respectively. chen et al., found that ldh had significantly increased in most patients, while albumin had decreased, but alt and ast showed no significant changes (11). the mentioned valthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e43 figure 1: area under the receiver operating characteristic curve of different laboratory parameters in predicting cases with positive rt-pcr for covid-19. table 1: comparing the laboratory parameters between the cases with positive and negative rt-pcr for covid-19 infection parameters total (n=200) rt-pcr for covid-19 p positive (n=70) negative (n=130) wbc (cell/mm3) 5962.8±2127 4043±1002 6894±1982 0.0001 neu (%) 51.9 60.7 47.8 0.0001 lym (%) 46.7 37.7 51.8 0.0001 positive crpa (%) 37 54 27.6 0.04 ast (iu/l) 28.6±8.6 32.1±8.01 26.8±8.3 0.001 alt (iu/l) 30±9.1 37.8±7.9 26.2±6.9 0.0001 ldh (u/l) 372.5±115 465.2±100.2 327.6±93.2 0.0001 urea (mg/dl) 28.6±8.01 34.6±8.6 25.8±5.8 0.001 albumin (g/dl) 3.5±0.9 2.9±0.8 3.7±0.8 0.0001 a crp test is qualitative and the indicated number shows the percentage of positive results in each group. abbreviations: white blood cell count (wbc), lymphocyte (lym), neutrophil (neu), aspartate aminotransferase (ast), alanine aminotransferase (alt), c-reactive protein (crp), and lactate dehydrogenase (ldh). ues were also reported for patients with mers-cov, where elevated alt, ast and ldh was observed (6). another study indicated that 2–11% of patients with covid-19 had liver comorbidities and 14–53% of cases had abnormal alt and ast levels during progression of covid-19 disease (12). furthermore, shi et al. studied patients whose covid-19 diagnothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. mardani et al. 4 table 2: the area under the receiver operating characteristic (roc) curve (auc) of the studied parameters in predicting cases with positive rt-pcr for covid-19 variables cut-off auc 95% ci p white blood cell (cells/mm3 ) 0.6 0.075 0.03-0.11 0.09 neutrophils (%) 0.70 0.858 0.79-0.92 <0.0001 lymphocyte (%) 0.6 0.112 0.05-0.16 0.12 positive c-reactive protein (%) 0.70 0.870 0.72-0.88 0.002 aspartate aminotransferase (iu/l) 0.40 0.716 0.63-0.8 <0.0001 alanine aminotransferase (iu/l) 0.40 0.879 0.82-0.93 <0.0001 lactate dehydrogenase (u/l) 0.70 0.835 0.76-0.9 <0.0001 urea (mg/dl) 0.70 0.831 0.76-0.9 <0.0001 albumin (g/dl) 0.6 0.242 0.15-0.32 0.04 ci: confidence interval. sis was confirmed by computed tomography (ct) scan while in the subclinical phase and found that incidence of ast abnormality among these patients was significantly lower than those diagnosed after the onset of symptoms (13). therefore, liver injury is more prevalent in severe cases compared to mild cases of covid-19. in another report, yang et al. found no difference in the incidence of abnormal liver function between survivors (30%) and non-survivors (28%) (9). liver damage in mild cases of covid-19 is often transient and can return to normal without any special treatment (12). we have found that the number and percentage of wbc, lym and neu were significantly different between positive and negative rt-pcr cases for covid-19/or sars-cov-2. in comparison to the normal range, we found low wbc and lym counts in patients with positive rt-pcr covid19, whereas neu counts were higher in these patients. in previous reports, low lym and wbc counts were found in most patients, which is in line with our study (14). laboratory studies showed leucopenia with leukocyte counts of 2.91 ãů 109 cells/l, 70.0% of which were neu (15). therefore, our result suggests that neu might not be affected with sars-cov-2 in the initial phase of the disease. it also suggests that sars-cov-2 might mainly act on lymphocytes, especially t lymphocytes, as does sars-cov. virus particles spread through the respiratory tract and infect other cells, inducing series of immune responses, and causing changes in number of peripheral white blood cells such as lymphocytes (11). some studies suggest that a substantial decrease in the total number of lymphocytes indicates that coronavirus affects many immune cells and inhibits cellular immune function (11). tsui and others reported that high neutrophil count on admission of covid-19 patients, and elevated ldh level were independent predictors of an adverse clinical outcome (16). in the present study, roc curve was used to analyze the specificity and sensitivity of different variables in suspected covid-19 patients. the auc of laboratory parameters such as alt, crp, ast, ldh, and neu indicated that they could be used to predict the presence of covid-19 disease, while those of albumin and wbc were below the reference line of roc curve, indicating that they were poor predictors of the disease. the data is in line with results reported by wang et al. (17) and gao et al. (4). in the current study, the auc of crp, alt, ldh, urea and neu were above 0.80; thus, they are effective and have very good predictive value for predicting covid-19. it seems that, some blood laboratory parameters could be used in screening cases with positive rt-pcr for covid-19. considering the significant difference in laboratory parameters evaluated in this study between the 2 groups, one can hope to model or predict the results of coronavirus testing based on routine laboratory tests. 5. limitation the sample size was relatively small. in addition, since this study was conducted on blood laboratory parameters, not every patient was continuously monitored for all clinical manifestations. 6. conclusion based on the findings of this study alt, crp, neu, ldh, and urea have very good accuracy in predicting cases with positive rt-pcr for covid-19, respectively. 7. declarations 7.1. acknowledgements the authors thank all their colleagues who co-operated in this investigation. 7.2. author contribution s.d.m.n and a.a.v conceived and designed experiments. m.k. and r.m performed the experiments. a.r.g, n.a, f.z and h.k analyzed the data. s.d.m.n. a.a.v and n.a wrote the paper. n.a revised and edited the paper. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e43 authors orcids rajab mardani: 0000-0001-7730-3040 abbas ahmadi vasmehjani: 0000-0001-8079-7352 fatemeh zali: 0000-0001-9098-4418 nayebali ahmadi: 0000-0002-8870-7267 hooman kaghazian: 0000-0003-4301-3381 alireza gholami: 0000-0003-0706-2821 mehdi kaviani: 0000-0002-9400-3207 seyed dawood mousavi nasab: 0000-0002-4831-3108 7.3. funding/support this study was supported by the proteomics research center of shahid beheshti university of medical sciences. 7.4. conflict of interest the authors have no conflicts of interest. references 1. organization wh. clinical management of severe acute respiratory infection (sari) when covid-19 disease is suspected: interim guidance, 13 march 2020. world health organization, 2020. 2. guan w-j, ni z-y, hu y, liang w-h, ou c-q, he j-x, et al. clinical characteristics of coronavirus disease 2019 in china. new england journal of medicine. 2020. 3. ai t, yang z, hou h, zhan c, chen c, lv w, et al. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases. radiology. 2020:200642. 4. gao y, li t, han m, li x, wu d, xu y, et al. diagnostic utility of clinical laboratory data determinations for patients with the severe covid-19. journal of medical virology. 2020. 5. fan be, chong vcl, chan ssw, lim gh, lim kge, tan gb, et al. hematologic parameters in patients with covidâăř19 infection. american journal of hematology. 6. al ghamdi m, alghamdi km, ghandoora y, alzahrani a, salah f, alsulami a, et al. treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (mers cov ) infection at a coronavirus referral center in the kingdom of saudi arabia. bmc infectious diseases. 2016;16(1):174. 7. wang j-t, sheng w-h, fang c-t, chen y-c, wang j-l, yu c-j, et al. clinical manifestations, laboratory findings, and treatment outcomes of sars patients. emerging infectious diseases. 2004;10(5):818. 8. rodriguez-morales aj, cardona-ospina ja, gutiãl’rrezocampo e, villamizar-pena r, holguin-rivera y, escalera-antezana jp, et al. clinical, laboratory and imaging features of covid-19: a systematic review and meta-analysis. travel medicine and infectious disease. 2020:101623. 9. yang x, yu y, xu j, shu h, liu h, wu y, et al. clinical course and outcomes of critically ill patients with sarscov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine. 2020. 10. kui l, fang y-y, deng y, liu w, wang m-f, ma j-p, et al. clinical characteristics of novel coronavirus cases in tertiary hospitals in hubei province. chinese medical journal. 2020. 11. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. 12. zhang c, shi l, wang f-s. liver injury in covid-19: management and challenges. the lancet gastroenterology & hepatology. 2020. 13. shi h, han x, jiang n, cao y, alwalid o, gu j, et al. radiological findings from 81 patients with covid-19 pneumonia in wuhan, china: a descriptive study. the lancet infectious diseases. 2020. 14. qu r, ling y, zhang yh, wei ly, chen x, li x, et al. plateletâăřtoâăřlymphocyte ratio is associated with prognosis in patients with corona virus disease-19. journal of medical virology. 2020. 15. lei j, li j, li x, qi x. ct imaging of the 2019 novel coronavirus (2019-ncov ) pneumonia. radiology. 2020:200236. 16. tsui pt, kwok ml, yuen h, lai st. severe acute respiratory syndrome: clinical outcome and prognostic correlates. emerging infectious diseases. 2003;9(9):1064. 17. wang y, liu y, liu l, wang x, luo n, ling l. clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with sars-coronavirus-2 in shenzhen, china. the journal of infectious diseases. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e25 ca s e re p o rt hepatic artery aneurysms as a rare but important cause of abdominal pain; a case series hamidreza haghighatkhah1, morteza sanei taheri1, seyed mohammadhadi kharazi1, maryam zamini1, sahar rabani khorasgani1∗, zahra jahangiri zarkani1 1. radiology department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: february 2019; accepted: march 2019; published online: 6 april 2019 abstract: hepatic artery aneurysm (haa) is the common visceral aneurysms with the highest reported rate of rupture. the clinical manifestations depending on the size of the aneurysm include epigastric pain, obstruction of biliary tract, rupture and death. imaging modalities like computed tomography (ct) scan and ct-angiography have a valuable role in the early detection of hhas. complications and selecting appropriate treatments depending on the size and location of the aneurysms. this article aimed to report clinical presentation, imaging finding and treatment of some patients presenting with haas to emergency department. keywords: aneurysm; hepatic artery; abdominal pain; abdomen, acute; angiography cite this article as: haghighatkhah h, sanei taheri m, kharazi s m, zamini m, rabani khorasgani s, jahangiri zarkani z. hepatic artery aneurysms as a rare but important cause of abdominal pain; a case series. arch acad emerg med. 2019; 7 (1): e25. 1. introduction hepatic artery aneurysm (haa) is a rare disease (0.002%– 0.4%) but is a clinically important phenomenon (1). haas are traditionally the second most common visceral aneurysms with an incidence of 20% and have the highest (44%) reported rate of rupture (2). the clinical manifestations depending on the size of the aneurysm include epigastric pain, obstruction of biliary tract, rupture and death. imaging modalities like computed tomography (ct) and ctangiography have a valuable role in the early detection of hha, its complications, and selecting appropriate treatments depending on the size and location of the aneurysms. in this case series, we reported 5 haa cases with different etiologies, presentations and treatments. 2. case presentations: 2.1. case 1 the first case was a 50-year-old man with acute-onset epigastric and right upper abdominal pain. abdominal ultrasonography demonstrated free abdominal fluid with internal clots. ct angiography was performed, which revealed a ruptured ∗corresponding author: sahar rabani khorasgani; department of radiology, shohadaye tajrish hospital, tajrish square, tehran, iran. email: rabani1369@yahoo.com tel: 009822721155 figure 1: a) axial contrast-enhanced ct (cect) scan demonstrate contrast filled saccular out-pouching at the level of the left hepatic artery (black arrow). hemoperitoneum with areas of higher attenuation indicates acute active bleeding is present. peripheral segmental liver hypo-densities due to de-vascularization and vasospasm are also evident. b) axial cect through the celiac trunk level shows left gastric artery aneurysm with intraluminal thrombosis. c) coronal maximum intensity projection (mip) reformation demonstrates concomitant aneurysm of hepatic artery (long arrow) and left gastric artery (short arrow). d) a volume-rendered 3d ct angiography image displays a small saccular left gastric artery aneurysm. proper haa with hemo-peritoneum in perihepatic space, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. haghighatkhah et al. 2 para-colic gutters, and massive abdominopelvic hematoma. a simultaneous visceral aneurysm was also detected at the origin of the left gastric artery. the exploratory laparotomy revealed 2.5 liters of hemo-peritoneum, a ruptured aneurysmal sac in proximal of the left branch of proper hepatic artery with surrounding clots and intact liver parenchyma. ligation in the proximal and distal parts of artery was done (figure 1). 2.2. case 2 the second patient was an 11-year-old boy with history of falling and blunt trauma to the flank and formation of liver hematoma. three weeks later, he was referred to emergency department with the chief complaint of abdominal pain. after proving pseudo-haa in contrast-enhanced computed tomography (cect) scan, the patient was referred for catheter base angiography and treated with coiled embolization (figure 2). figure 2: e, f) axial contrast-enhanced ct (cect) scan in arterial phase reveals out-pouching pseudo-aneurysm in hepatic artery branch along with intra parenchymal and sub-capsular liver hematoma (arrow). g) selective digital subtraction angiography (dsa) from hepatic artery shows large pseudo-aneurysm in right hepatic artery. the patient underwent coil embolization for treatment of aneurysm. h) aneurysm disappears after embolization. 2.3. case 3 the patient was a 66-year-old male with epigastric pain and nausea for 10 days. past medical history revealed smoking with hypertension. ct angiography showed saccular aneurysm in proper hepatic artery. the patient underwent surgical repair. a 70 × 70 mm aneurysmal lesion at the origin of proper hepatic artery was found in lesser sac and gastrohepatic ligament. after attaining control of proper hepatic artery, end-to-end bypass graft was done in hepatic artery using saphenous vein. after 12t h post-operative day hospitalization, the patient referred to the hospital a week later with severe abdominal pain and vomiting. in ct scan, there was evidence of acute necrotizing pancreatitis, along with collection in liver. the patient was successfully managed with conservative treatment and discharged after two weeks without major complication (figure 3). figure 3: figure 3: i, j) axial computed tomography (ct) angiogram showing spontaneous saccular aneurysm in proper hepatic artery with peripheral thrombosis and internal diameter of 44 mm, and evidence of hematoma (white arrow) with compression to second part of duodenum and the head of pancreas. k) volumerendered 3d ct angiography image displays aneurysm from common hepatic artery (red arrow) and hematoma (black arrow) below it. l) the patient was referred one week after surgical repairing following abdominal pain. contrast-enhanced ct (cect) scan finding showed necrotizing center with severe edema around the head of pancreas with extension to porta-hepatis, peri-portal, and anterior sub-hepatic space suggestive of acute necrotizing pancreatitis. 2.4. case 4 the patient was a 4-year-old boy with history of blunt trauma to his right flank. one month later, the patient admitted with melena, hematemesis, and epigastric pain. color doppler ultrasonography, cect scan, and magnetic resonance imaging (mri) showed haa. the patient was treated successfully with coiled embolization (figure 4). 2.5. case 5 the patient was a 24-year-old male with history of gunshot traumatization and surgery due to hepatic artery aneurysm and liver hematoma. he was referred due to re-bleeding and large liver-infected hematoma. the patient underwent successful coil embolization similar to case 2. 3. discussion true haas are mostly due to degenerative or dysplastic change of the extrahepatic vessels. their main cause is atherosclerosis (3), although vasculitis have also been reported (4). pseudo-haas, accounting for approximately 20% of all haas (5), can be as intrahepatic or extrahepatic. approximately 80% of aneurysms of the hepatic artery are extrahepatic which are mostly spontaneous, usually due to imthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e25 figure 4: a) ultrasound showed a hyper echo heterogeneous illdefined lesion (arrow) in the right lobe of liver measuring 30*40 mm in favor of hematoma. b) axial contrast-enhanced ct scan correlated with ultrasound finding (arrow). the patient underwent conservative treatment. c, d, e) one month later, ultrasound revealed a 23*23 mm hyper echo lesion with central 14*14 mm hypo echo vascular area in segment 8 of liver (an aneurysmal lesion). f) axial t2w mri showed a round hyper signal lesion (arrow), the same signal with aorta. g, h) selective digital subtraction angiography (dsa) from right hepatic artery shows pseudo-aneurysm in right hepatic artery. the patient underwent coil embolization for treatment of aneurysm (arrow) and aneurysm disappeared after embolization (arrow). munosuppression, biloma, and biliary tract infection (2, 6). the causes of intrahepatic pseudo-aneurysms are usually iatrogenic (liver transplantation, cholecystectomy, etc.), although they still have a potential for severe hemorrhage (6). the clinical manifestations tend to be non-specific, depending on the size of the aneurysm. although small haas are often asymptomatic, the natural history is for progressive enlargement with increasing risk of rupture and death. haas may cause right upper quadrant and epigastric pain or obstruction of biliary tract. the classic triad of quinke’s, i.e., obstructive jaundice, abdominal pain and hemobilia, is seen in 30% of the patients (7). inflammation associated with sepfigure 5: i, j, k) axial contrast enhanced computed tomography (cect) scan in arterial phase and coronal reformatted images from liver show pseudo-aneurysm in right hepatic artery (arrow) with infected liver hematoma containing gas density and also sub-capsular hematoma. tic emboli may erode the arterial wall and then prompt haa rupture, causing hemobilia (8). the presence of a common channel for both pancreatic and biliary ducts with no accessory duct drainage is predisposed to the development of acute pancreatitis due to the blockage of the pancreatic duct by blood clot (9). multiple diagnosis tests are used, such as abdominal ultrasound, ct, ct angiography, mri, endoscopy and angiography. angiography is a therapeutic modality of choice in splanchnic aneurysms through embolization (10). the sensitivity and specificity of multi-detector computed tomographic angiography to diagnose aneurysm of the hepatic arteries was 100% (11). the size and location of the aneurysm, patient age and comorbidities have critical role in determining the specific approach (12). trans-arterial embolization (tae) has a high rate of success for all causes of haa (13). for intrahepatic aneurysms, embolization is the accepted treatment (3). surgical treatment of ruptured haas can be allocated when the patient is in an unstable condition, the aneurysm is extrahepatic or larger than 2 cm, and endovascular intervention fails (1). lee et al. reported an incidental large haa and the patient was undergone open surgery for aneurysmectomy and the proper hepatic artery was anastomosed with gastrodeodenal artery (14). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. haghighatkhah et al. 4 4. discussion visceral aneurysms such as hepatic artery aneurysm should be considered as a rare but important differential diagnosis of acute abdominal pain. all emergency physicians and surgeons should kept this diagnosis in their mind to prevent from its life threatening complications. 5. ethical statement all patients were followed up with a detailed description of the purpose of the research and written consent was obtained. patient names were not included in the study and coding was used to classify the information. the benefits of participation in the plan were to undertake an important step in managing patients with similar disease. the cost of participation in the scheme was free. 6. appendix 6.1. acknowledgements none. 6.2. authors contribution the author met the standard criteria for authorship based on the recommendations of the international committee of medical journal editors. authors orcids hamidreza haghighatkhah: 0000-0001-5411-0609 morteza sanei taheri: 0000-0002-8881-9058 sahar rabani khorasgani: 0000-0001-7927-6429 6.3. conflict of interest none. 6.4. funding no fund has been received. references 1. altaca g. ruptured aneurysm of replaced left hepatic artery as a cause of haemorrhagic shock: a challenge of diagnosis and treatment. interactive cardiovascular and thoracic surgery. 2011;14(2):220-2. 2. arneson ma, smith rs. ruptured hepatic artery aneurysm: case report and review of literature. annals of vascular surgery. 2005;19(4):540-5. 3. dolapci m, ersoz s, kama na. hepatic artery aneurysm. annals of vascular surgery. 2003;17(2):214-6. 4. huisman m, van den bosch ma, mooiweer e, molenaar iq, van herwaarden ja. endovascular treatment of a patient with an aneurysm of the proper hepatic artery and a duodenal fistula. journal of vascular surgery. 2011;53(3):814-7. 5. bennett j, fay d, krysztopik r. right hepatic artery false aneurysm secondary to acalculous cholecystitis. case reports. 2010;2010:bcr0820103258. 6. jeng k-s, huang c-c, lin c-k, lin c-c, liang c-c, chung c-s, et al., editors. early detection of a hepatic artery pseudoaneurysm after liver transplantation is the determinant of survival. transplantation proceedings; 2016: elsevier. 7. turkvatan a, okten r, kelahmet e, ozdemir e, olcer t. hepatic artery aneurysm: imaging findings. j ankara univ fac med. 2005;58:73-5. 8. yu yh, sohn jh, kim ty, jeong jy, han ds, jeon yc, et al. hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis. world journal of gastroenterology: wjg. 2012;18(18):2291. 9. mee as, turner ja, gow nm. recurrent acute pancreatitis due to haemobilia from a hepatic artery aneurysm. postgraduate medical journal. 1983;59(695):590-2. 10. bernal adpa, loures p, calle jco, cunha b, cordoba jc. right hepatic artery aneurysm. revista do colegio brasileiro de cirurgioes. 2016;43:401-3. 11. kayahan ulu em, coskun m, ozbek o, tutar nu, ozturk a, aytekin c, et al. accuracy of multidetector computed tomographic angiography for detecting hepatic artery complications after liver transplantation. transplantation proceedings. 2007;39(10):3239-44. 12. saeed h, buxey kn, milne cpe, cox g. quinke’s triad: haemobilia secondary to hepatic artery aneurysm. anz journal of surgery. 2017. 13. alrajraji m, nawawi a, jamjoom r, qari y, aljiffry m. delayed hemobilia due to hepatic artery pseudo-aneurysm: a pitfall of laparoscopic cholecystectomy. bmc surgery. 2016;16(1):59. 14. lee d, chung bh, heo sh, park yj, kim di. case report of a large common hepatic artery aneurysm. ann vasc surg. 2018;52:316.e11-.e13. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentations: discussion discussion ethical statement appendix references emergency. 2018; 6 (1): e15 or i g i n a l re s e a rc h the accuracy of ultrasonography in detection of ulnar collateral ligament of thumb injuries; a cross-sectional study babak shekarchi1, mohammadreza mokhdanzadeh dashti2, mostafa shahrezaei3, ebrahim karimi2∗ 1. radiology department, imam reza hospital, aja university of medical sciences, faculty of medicine, tehran, iran. 2. emergency department, be’sat hospital, aja university of medical sciences, faculty of medicine, tehran, iran. 3. orthopedics department, imam reza hospital, aja university of medical sciences, faculty of medicine, tehran, iran. received: january 2018; accepted: february 2018; published online: 19 february 2018 abstract: introduction: timely diagnosis and treatment of traumatic injury to ulnar collateral ligament (ucl) of thumb is of special importance for preserving the full function of the hand. therefore, the present study has been designed with the aim of evaluating the accuracy of ultrasonography in detection of these injuries. methods: the present diagnostic accuracy study was performed on trauma patients over 15 years old who had clinical evidence of injury to ucl of thumb and were admitted to the emergency department. all patients were evaluated regarding injury to the mentioned ligament via ultrasonography and mri and finally, the accuracy of ultrasonography in this regard was measured considering mri as the reference test. results: 20 individuals with the mean age of 38.60 ± 13.45 (16 – 64) years were evaluated (60% male). based on ultrasonography and mri findings 7 (35%) individuals and 7 (35%), respectively had complete ligament rupture (kappa: 0.560 (95% ci: 0.179 – 0.942)). sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of ultrasonography in detecting injuries of the mentioned ligament were 71.42 (30.25 – 94.88), 84.61 (53.66 – 97.28), 71.42 (30.25 – 94.88), 84.61 (53.66 – 97.28), 2.5 (0.71 – 8.82), and 0.18 (0.04 – 0.67), respectively. conclusion: based on the findings of the present study, performance of ultrasonography by a radiologist in the emergency department has 80% accuracy in detecting traumatic injuries of ucl of the thumb. keywords: ultrasonography; collateral ligament, ulnar; injuries; magnetic resonance imaging; dimensional measurement accuracy © copyright (2018) shahid beheshti university of medical sciences cite this article as: shekarchi b, mokhdanzadeh dashti m, shahrezaei m, karimi e. the accuracy of ultrasonography in detection of ulnar collateral ligament of thumb injuries; a cross-sectional study. emergency. 2018; 6(1): e15. 1. introduction u lnar collateral ligament (ucl) of thumb is one of the major protective ligaments of metacarpophalangeal joint (1). damage to this ligament usually happens following hyper-abduction or hyper-extension of the mentioned joint (2, 3). this injury is among the most common injuries of thumb with a frequency of 50 cases in 100000 population each year, following accidents and trauma and sports injuries (2, 4-7). rupture of this ligament leads to decrease in ∗corresponding author: ebrahim karimi; emergency department, be’sat hospital, afsariyeh highway, hejrat boulevard, tehran, iran. email: ebrahimkarimi86@gmail.com tel: +989124544838 the ability of the patient to hold objects and make a fist using the thumb and therefore, timely diagnosis and treatment of this injury is very important for preserving the function of the hand (8, 9). diagnosis of injury to this ligament is mostly based on clinical examination and inability to bear pressure on the thumb in the valgus position (10). plain radiography, ultrasonography, and magnetic resonance imaging (mri) are available imaging tools for evaluating ucl injuries of thumb. plain radiography shows fractures properly and ultrasonography and mri are good for showing the details of injury to soft tissue (11-13). sensitivity and specificity of mri in detection of ucl of thumb have been estimated as 100% in a study by harper et al. (14). however, the accuracy of ultrasonography in detection of this type of injuries has varied from 40% to 92% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. shekarchi et al. 2 between various studies (15-18). since ultrasonography has become an available and inexpensive tool in most emergency departments, there is an increasing inclination towards using ultrasonography in detection of various problems in patients. therefore, the present study has been designed with the aim of evaluating the accuracy of ultrasonography in detection of traumatic injuries of ucl of thumb. 2. methods 2.1. study design and setting the present diagnostic accuracy study was performed on trauma patients who had clinical evidence of injury to ucl of thumb and were admitted to the emergency department of be’sat hospital, tehran, iran, over a period of 2 years. all the patients were evaluated regarding injury to the mentioned ligament via ultrasonography and then mri and finally, the accuracy of ultrasonography in this regard was measured considering mri as the reference test. protocol of the present study was approved by the ethics committee of aja university of medical sciences and all researchers adhered to the principles of helsinki declaration. before inclusion in the study, informed written consent for participation in the study was obtained from the patients or their companions. 2.2. participants participants of the present study consisted of patients over 15 years of age who had clinical evidence of traumatic injury to ucl of metacarpophalangeal joint of the thumb that were included via consecutive non-probability sampling. those with non-traumatic injuries of ucl, visible fracture and rupture at the anatomic site under evaluation, and also those who did not cooperate in performing imaging were excluded from the study. no sex limitation was considered in the present study. 2.3. imaging ultrasonography of tendon was performed by a skilled radiologist using ge voluson e8 bt10 device and 12mhz linear probe of msk system. in addition, mri of the tendon was done using a 1.5 tesla device and from t1 view for anatomical interpretation and t2 view for pathological interpretation. injuries were reported as complete rupture, without rupture, and/or with minor rupture. the radiologist interpreting mri and the sonologist were not aware of each other’s findings and the clinical findings of the patient. 2.4. data gathering data gathering was done by a senior emergency medicine resident using a pre-designed checklist including demographic data of the patients (age, sex, height, and weight) as well as ultrasonography and mri findings regarding injury of ucl. in this study presence of tenderness at the time of performing valgus stress test and also valgus stress range more than 30 degrees (15-30 = normal) were considered as clinical evidence of probable injury of ucl (19). 2.5. statistical analysis minimum sample size required for the present study, considering 15% prevalence of ucl injury (20), 95% confidence interval, 0.17 precision and considering 15% probability of loss samples was estimated as 20 cases. data underwent statistical analysis using spss 21 statistical software. data were presented as frequency (%) or mean ± standard deviation. for calculating sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and accuracy of ultrasonography in detection of traumatic injuries of ucl with 95% confidence interval, vassarstats medical calculator was used. in this study, mri was considered as the reference test. for evaluating the agreement rate between the findings of ultrasonography and mri, calculation of kappa coefficient with 95% confidence interval was applied. in this study, kappa coefficient less than 0.20 was considered as little agreement, 0.21 – 0.40 as poor, 0.41 – 0.60 as average, 0.61 – 0.80 as good and 0.81 – 1.00 as very good. 3. results 20 individuals with the mean age of 38.60 ± 13.45 (16 – 64) years were evaluated (60% male). table 1 depicts the baseline characteristics of the studied patients. most patients were in the 30 – 45 years age group (45%). mean body mass index (bmi) of the patients was 22.95 ± 3.02. based on ultrasonography findings 7 (35%) individuals had complete rupture of ucl of thumb and others had minor ruptures or no rupture at all. based on mri findings, these rates were 7 (35%) individuals with complete rupture, and 13 (65%) patients without or with minor injuries. agreement rate between the findings of ultrasonography and mri based on calculation of kappa coefficient was 0.560 (95% ci: 0.179 – 0.942). table 2 shows the screening performance characteristics of ultrasonography in detecting injuries of ucl of thumb in comparison with mri. the overall accuracy of ultrasonography in the mentioned field was estimated as 0.80 (95%ci: 65.34 – 94.27). 4. discussion based on the results of the present study, performance of ultrasonography by a radiologist in the emergency department has 80% accuracy in detecting traumatic injuries of ucl of the thumb. rate of agreement between the findings of ultrasonography and mri in this regard was estimated as average. it seems than considering its relatively low sensitivity, ultrathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e15 table 1: baseline characteristics of the studied patients variable values sex male 12 (60) female 8 (40) age (year) < 30 5 (25) 30 – 45 9 (45) ≥ 45 6 (30) body mass index 18.5 – 25 12 (60) ≥ 25 8 (40) height (m) 1.76 ± 0.07 weight (kg) 77.5 ± 11.9 data are presented as mean ± standard deviation or frequency and percentage. table 2: screening performance characteristics of ultrasonography in detection of traumatic injuries of ulnar collateral ligament of the thumb in comparison with mri characteristics values (95% ci) true positive 5 false positive 2 true negative 11 false negative 2 sensitivity 71.42 (30.25 – 94.88) specificity 84.61 (53.66 – 97.28) positive predictive value 71.42 (30.25 – 94.88) negative predictive value 84.61 (53.66 – 97.28) positive likelihood ratio 2.5 (0.71 – 8.82) negative likelihood ratio 0.18 (0.04 – 0.67) sonography cannot yet be used as a proper screening tool in detecting injuries of ucl of thumb. sensitivity and specificity of mri in detecting injuries of ucl of thumb in various studies have been estimated as 96% to 100%, and 100%, respectively and it is currently considered as the standard test in detection of these injuries (14, 15, 21). of course, detection of tendon injuries using mri has its own complications and requires skill of the interpreter. despite ultrasonography being available, portable, and costing less, it also depends on the operator and therefore, its accuracy varies widely and has been reported as 40% to 92% in different studies (17, 18, 22). in a study by melville et al. in 2013 sensitivity and specificity of ultrasonography method were estimated to be about 100% (23). in contrast, papandrea et al. in 2008 estimated sensitivity and specificity of ultrasonography to be 76% and 81%, respectively. in addition, the positive and negative predictive values of ultrasonography were estimated to be 74% and 87%, respectively, in the mentioned study (16). the results of the present study are in agreement with the studies performed in this regard to a great extent. in this study, attempts were made to eliminate limitations such as training and insufficient skill of the operator by asking a radiologist to perform the ultrasonography. but despite the performance of ultrasonography by a radiologist, the number of false positive and false negative cases or in other words incorrect report was relatively significant (4 cases out of 20 reports or 20%). the first studies carried out in the field of assessing the diagnostic accuracy of ultrasonography in detecting ulc of thumb injuries belong to 1980 to 2000. maybe the reason for ultrasonography not being known as a proper method for widespread use in this regard is that first, the mentioned problem is not a life-threatening emergency and suspected cases in clinical examination will not undergo further interventions and following fixation, will be visited by an orthopedic specialist or a surgeon with delay. second, since a radiologist is not available at all times of the day, even if the accuracy of this method is high it will not be available 24 hours a day. in addition, if emergency medicine specialists gain the required skill in this regard by undergoing special trainings, surgeons and orthopedic specialists will not rely on it for planning surgery and will apply more accurate methods such as mri. therefore, despite the numerous advantages of bedside ultrasonography in the emergency department, we should be cautious about its type of application and exaggeration of its abilities. the wide confidence interval of likelihood ratio of ultrasonography in detection of the mentioned tendon’s injuries challenges it as a proper screening test. it seems that in the presence of a low-risk and accurate method such as mri, performing ultrasonography cannot be of much help in management of these patients and accurate planning regarding their need for repair. 5. limitation small sample size might be the most important limitation in generalizing the findings. in this study by blinding the sonologist and mri interpreter to the clinical data, we tried to prevent any bias in this regard. 6. conclusion based on the findings of the present study, performance of ultrasonography by a radiologist in the emergency department has 80% accuracy in detecting traumatic injuries of ucl of the thumb. rate of agreement between the findings of ultrasonography and mri in this regard was estimated as average. it seems than considering its relatively low sensitivity, ultrasonography cannot yet be used as a proper screening tool in detecting injuries of ucl of thumb. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com b. shekarchi et al. 4 7. appendix 7.1. acknowledgements all the staff members of the emergency department of be’sat hospital are thanked for their cooperation throughout the study period. 7.2. author contribution all authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict of interest in any phase of performing the study. references 1. tang p. collateral ligament injuries of the thumb metacarpophalangeal joint. journal of the american academy of orthopaedic surgeons. 2011;19(5):287-96. 2. werner bc, belkin ns, kennelly s, weiss l, barnes rp, rodeo sa, et al. injuries to the collateral ligaments of the metacarpophalangeal joint of the thumb, including simultaneous combined thumb ulnar and radial collateral ligament injuries, in national football league athletes. the american journal of sports medicine. 2017;45(1):195-200. 3. giele h, martin j. the two-level ulnar collateral ligament injury of the metacarpophalangeal joint of the thumb. journal of hand surgery. 2003;28(1):92-3. 4. baskies ma, lee sk. evaluation and treatment of injuries of the ulnar collateral ligament of the thumb metacarpophalangeal joint. bulletin of the nyu hospital for joint diseases. 2009;67(1):68. 5. keramidas e, miller g. adult hand injuries on artificial ski slopes. annals of plastic surgery. 2005;55(4):357-8. 6. patel s, potty a, taylor ej, sorene ed. collateral ligament injuries of the metacarpophalangeal joint of the thumb: a treatment algorithm. strategies in trauma and limb reconstruction. 2010;5(1):1-10. 7. jones m, england s, muwanga c, hildreth t. the use of ultrasound in the diagnosis of injuries of the ulnar collateral ligament of the thumb. journal of hand surgery. 2000;25(1):29-32. 8. mitsionis g, varitimidis s, sotereanos g. treatment of chronic injuries of the ulnar collateral ligament of the thumb using a free tendon graft and bone suture anchors. journal of hand surgery. 2000;25(2):208-11. 9. basar h, basar b, kaplan t, erol b, tetik c. comparison of results after surgical repair of acute and chronic ulnar collateral ligament injury of the thumb. chirurgie de la main. 2014;33(6):384-9. 10. avery dm, caggiano nm, matullo ks. ulnar collateral ligament injuries of the thumb: a comprehensive review. orthopedic clinics. 2015;46(2):281-92. 11. ritting aw, baldwin pc, rodner cm. ulnar collateral ligament injury of the thumb metacarpophalangeal joint. clinical journal of sport medicine. 2010;20(2):106-12. 12. schnur dp, delone fx, mcclellan rm, bonavita j, witham rs. ultrasound: a powerful tool in the diagnosis of ulnar collateral ligament injuries of the thumb. annals of plastic surgery. 2002;49(1):19-23. 13. arend cf, da silva tr. the role of us in the evaluation of clinically suspected ulnar collateral ligament injuries of the thumb: spectrum of findings and differential diagnosis. acta radiologica. 2014;55(7):814-23. 14. harper mt, chandnani vp, spaeth j, santangelo jr, providence bc, bagg ma. gamekeeper thumb: diagnosis of ulnar collateral ligament injury using magnetic resonance imaging, magnetic resonance arthrography and stress radiography. journal of magnetic resonance imaging. 1996;6(2):322-8. 15. hergan k, mittler c, oser w. ulnar collateral ligament: differentiation of displaced and nondisplaced tears with us and mr imaging. radiology. 1995;194(1):65-71. 16. papandrea rf, fowler t. injury at the thumb ucl: is there a stener lesion? journal of hand surgery. 2008;33(10):1882-4. 17. hergan k, mittler c. sonography of the injured ulnar collateral ligament of the thumb. bone & joint journal. 1995;77(1):77-83. 18. susic d, hansen br, hansen tb. ultrasonography may be misleading in the diagnosis of ruptured and dislocated ulnar collateral ligaments of the thumb. scandinavian journal of plastic and reconstructive surgery and hand surgery. 1999;33(3):319-20. 19. heyman p, gelberman rh, duncan k, hipp ja. injuries of the ulnar collateral ligament of the thumb metacarpophalangeal joint: biomechanical and prospective clinical studies on the usefulness of valgus stress testing. clinical orthopaedics and related research. 1993;292:165-71. 20. carr d, johnson rj, pope mh. upper extremity injuries in skiing. the american journal of sports medicine. 1981;9(6):378-83. 21. plancher kd, ho cp, cofield ss, viola r, hawkins rj. role of mr imaging in the management of" skier’s thumb" injuries. magnetic resonance imaging clinics of north america. 1999;7(1):73-84. 22. ahn jm, sartoris dj, kang hs, botte m, trudell d, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e15 haghighi p, et al. gamekeeper thumb: comparison of mr arthrography with conventional arthrography and mr imaging in cadavers. radiology. 1998;206(3):737-44. 23. melville d, jacobson ja, haase s, brandon c, brigido mk, fessell d. ultrasound of displaced ulnar collateral ligament tears of the thumb: the stener lesion revisited. skeletal radiology. 2013;42(5):667-73. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e29 or i g i n a l re s e a rc h pre-hospital delay and its contributing factors in patients with st-elevation myocardial infarction; a cross sectional study hamidreza poorhosseini1, mohammad saadat2, mojtaba salarifar1, seyedeh hamideh mortazavi2, babak geraiely1∗ 1. interventional cardiology department, tehran heart center, tehran university of medical sciences, tehran, iran. 2. cardiology department, tehran heart center, tehran university of medical sciences, tehran, iran. received: march 2019; accepted: april 2019; published online: 29 may 2019 abstract: introduction: the outcome of st-elevation myocardial infarction (stemi) is significantly influenced by the total tissue ischemic time. in spite of efforts for reducing the in-hospital delay by full-time provision of primary percutaneous coronary intervention (p-pci) in the 24/7 program, pre-hospital delay still persists. as a first report in iran, we aimed to assess the duration of pre-hospital delay and its contributing factors in stemi patients in the p-pci era. methods: the present cross-sectional study evaluated 2103 stemi patients who underwent primary pci from 2016 to 2018. demographic, personal and socioeconomic factors, index event characteristics, past medical history, pain onset and door times of patients were recorded and independent factors of prehospital delay were calculated. results: median (iqr) of pain to door (p2d) time was 279 (120-630) minutes. in multivariate analysis, female gender [beta=0.064 (95%ci: 0.003-0.125); p=0.038], being uneducated [beta=0.213 (95%ci: 0.115-0.311); p<0.001], the onset of chest pain between 00:00 to 6:00 [beta=0.130 (95%ci: 0.058-0.202); p<0.001] or 7:00 to 12:00 [beta=0.119 (95%ci: 0.049-0.190); p=0.001], self-transportation [beta=0.098 (95%ci: 0.015-0.181); p=0.020] or referral from another hospital [beta=0.253 (95%ci: 0.117-0.389); p<0.001], atypical chest pain [beta=0.170 (95%ci: 0.048-0.293); p=0.006], history of hypertension [beta=0.052 (95%ci: 0.002-0.102); p=0.041], and opium abuse [beta=0.076 (95%ci: 0.007-0.146); p=0.031] were associated with significantly higher log(p2d), while history of cabg was associated with shorter p2d. conclusion: our study showed that p2d is still very high in iran and revealed the high-risk groups associated with longer p2d. effective actions should be implemented to increase the public awareness about the symptoms of stemi, and the importance of immediate appropriate help-seeking. keywords: st-elevation myocardial infarction; myocardial infarction, stemi; time-to-treatment cite this article as: poorhosseini h, saadat m, salarifar m, mortazavi s h, geraiely b. pre-hospital delay and its contributing factors in patients with st-elevation myocardial infarction; a cross sectional study. arch acad emerg med. 2019; 7(1): e29. 1. introduction ischemic heart disease is still the most common cause of death worldwide (1-3). several studies have shown that the morbidity and mortality of patients with st-elevation myocardial infarction (stemi) is significantly influenced by the total tissue ischemic time, which consists of pre-hospital and/or in-hospital delays (4-7). high expenditure strategies like primary percutaneous coronary intervention (p-pci) for ∗corresponding author: babak geraiely; tehran heart center, north kargar street, tehran-iran, p.o: 1411713138, tel & fax: +98 21 88029600, email: bgeraiely@sina.tums.ac.ir stemi and early invasive strategy for non-stemi are developed to reduce the in-hospital component of ischemic time; while a huge amount of golden time is lost in the pre-hospital phase. efforts have been made in different countries to reduce the total ischemic time. while in-hospital delay has been reduced in many countries, even developing ones (8, 9), only developed countries have been able to reduce the prehospital delay by focusing on total ischemic time through increasing the general population’s awareness via public educational programs in social media (10, 11). due to the implementation of full-time (24/7) provision of p-pci services in our country by the ministry of health and medical education, the in-hospital delay has been reduced in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. poorhosseini et al. 2 recent years (12). however, as long as the pre-hospital delay remains too long, the benefits of 24/7 p-pci will be limited. there is no large-scale study evaluating the accurate duration of pre-hospital delay in stemi patients in our country. given this lack of information, we aimed to assess the duration of prehospital delay and it’s contributing factors in stemi patients undergoing p-pci. 2. methods 2.1. study design and setting in the present cross-sectional study, we enrolled 2407 consecutive stemi patients who underwent p-pci between january 2016 and december 2018 at a tertiary cardiac center (tehran heart center)(13), tehran, iran. the hospital’s local review board and ethics committee approved the study protocol (ethics number: ir.tums.medicine.rec.1397.954). 2.2. participants the study population consisted of all stemi patients who were referred to the mentioned hospital during the study period and underwent p-pci. patients were excluded if the stemi had occurred in the hospital (n=23). in addition, patients with missed data on pain or door times were excluded from the analysis (n=281). finally, 2103 stemi patients were included. 2.3. data gathering data on the patients’ demographic information, personal and socioeconomic factors, marital status, educational level, ethnicity, place of longest stay, insurance type, physical activity level, mode of transfer to hospital, pain characteristics, pain onset time, door times, cardiovascular risk factors, and patients’ past medical history, as well as the infarct related artery were extracted from ischemic heart disease, angiography and angioplasty registries of the hospital, which have been described in details before (14). physical activity level was defined as high in professional athletes, intermediate in those who do usual daily activities and low in patients with the least or lack of physical activity. 2.4. statistical analysis continuous variables were presented as mean ± standard deviations (sds) if they assumed normal distributions and as medians (25t h – 75t h interquartile ranges: iqr) if they failed to assume normal distributions. discrete variables were presented as numbers (percentages). pain to door (p2d) was compared between groups using mann–whitney test and kruskal–wallis test as appropriate. the predictors exhibiting a borderline statistical relationship with pain to door time in the univariate analysis (p ≤ 0.15) were taken for a multivariate logistic regression analysis to investigate their independence. backward elimination regression analysis was used to remove insignificant variables and log(p2d) was considered as a dependent variable. a p ≤ 0.05 was considered statistically significant. all the statistical analyses were conducted using ibm spss statistics for windows, version 24.0 (ibm corp, armonk, ny). 3. results 3.1. baseline characteristics of participants 2407 consecutive patients were studied out of which 23 cases were excluded due to occurrence of stemi within the hospital and 281 were excluded because of missed data on pain or door times. finally, 2103 stemi patients with the mean age of 59.49±11.79 years were enrolled for analysis (76.4% male). table 1 and 2 summarize the baseline characteristics of studied patients. 94.3% of the patients were married, 79.0% had a diploma or university level education, 77.1% were of fars ethnicity. self-transport was the most common form of transfer (86%). table 3 shows the index event’s characteristics. median (iqr) of p2d time of patients was 279 (120-630) minutes. 3.2. contributing factors of p2d delay (univariate analysis) the results of univariate analysis are presented in table 13. based on these analyses, female gender was associated with longer median of p2d time (p<0.001) and higher educational level was associated with shorter p2d time (p<0.001). age had a significant relationship (r=0.036, p=0.095) with log(p2d), while the association was insignificant for bmi (r=0.004, p=0.865). the p2d time was significantly shorter in those who were transferred to the hospital by ems (p<0.001). despite the presence of some meaningful patterns, statistical significance was not observed regarding marital status (p=0.137) and physical activity status (p=0.507). description of symptoms as atypical or typical chest pain (p=0.005) and also epigastric pain (p=0.007) was significantly associated with longer p2d. in addition, the history of diabetes (p=0.029) and hypertension (p=0.004) were associated with longer p2d. although p2d was not different among those with and without the history of coronary stenting (p=0.924), the history of coronary artery bypass graft (cabg) was associated with shorter p2d with borderline significance [191.0 (97.50425.50) vs. 280.0 (120.0-630.0), p=0.085]. 3.3. contributing factors of p2d delay (multivariate analysis) after nine steps of the backward elimination method, eight variables remained in the final model (table 4). female gender (beta-coefficient: 0.064, 95%ci: 0.003 0.125, p= 0.038), being uneducated (beta: 0.213, 95%ci: 0.115 0.311, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e29 table 1: demographic and socioeconomic characteristics variables number (%) prehospital delay (minute) p median iqr 25% 75% gender male 1607(76.4) 255.00 110.00 595.00 <0.001 female 496 (23.6) 337.00 160.00 790.00 marital status married 1983 (94.3) 270.50 117.00 619.75 0.173 single 17 (0.8) 314.00 122.50 625.50 divorced 18 (0.9) 227.50 83.00 1020.25 widowed 85 (4.0) 349.00 172.50 858.00 education university 279 (13.4) 206.00 90.00 465.00 <0.001 high school diploma 1362 (65.6) 265.00 115.00 606.75 elementary education 175 (8.4) 310.00 136.00 662.00 uneducated 260 (12.5) 400.50 184.25 1014.00 ethnicity fars 1622 (77.1) 270.00 117.00 603.75 turk 299 (14.2) 303.00 130.00 730.00 0.267 other 182 (8.7) 318.00 120.00 806.00 longest linger tehran 1507 (71.7) 260.00 110.00 603.25 0.011 main cities 162 (7.7) 355.00 141.00 732.50 small cities 161 (7.7) 312.00 140.25 689.75 village 273 (13.0) 300.00 138.00 659.50 insurance social security 843 (40.1) 273.00 120.00 648.50 0.609 health facilities 704 (33.5) 285.00 120.25 625.75 other companies 390 (18.5) 289.00 120.00 600.00 no insurance 166 (7.9) 239.00 90.75 601.50 physical activity level high 49 (2.3) 206.00 128.75 574.00 intermediate 1986 (94.4) 279.00 118.50 624.50 0.507 low 68 (3.2) 310.00 129.00 790.00 p<0.001), the onset of chest pain in 00:00 to 6:00 (beta: 0.130, 95%ci: 0.058 0.202, p<0.001) or 7:00 to 12:00 (beta: 0.119, 95%ci: 0.049 0.190, p=0.001), self-transportation (beta: 0.098, 95%ci: 0.015 0.181, p=0.020) or referral from another hospital (beta: 0.253, 95%ci: 0.117 0.389, p<0.001), description of symptoms as atypical chest pain (beta: 0.170, 95%ci: 0.048 0.293, p=0.006), history of hypertension (beta: 0.052, 95%ci: 0.002 0.102, p=0.041), and opium abuse (beta: 0.076, 95%ci: 0.007 0.146, p=0.031) were associated with longer p2d and the history of cabg (beta: -0.124, 95%ci: -0.252 -0.004, p=0.048) was associated with shorter p2d time. 4. discussion based on the findings of the present study, female gender, being uneducated, the onset of chest pain in 00:00 to 6:00 or 7:00 to 12:00, self-transportation or referral from another hospital, description of symptoms as atypical chest pain, history of hypertension and opium abuse were associated with longer p2d while history of cabg was associated with shorter p2d time. several studies have been performed in different countries to estimate the interval between pain onset and hospital arrival time. table 5 demonstrates the median of prehospital delay in stemi patients in various countries. as is evident grossly, developed countries have succeeded in reducing p2d to around 2 hours, while india as a developing country hasn’t shown any obvious progress during these years. limited studies with small sample sizes have been conducted regarding prehospital delay in iran (table 6). as is evident, all of them were performed before implementation of 24/7 program. except for one study, all of them have small sample sizes and their results are greatly discordant. to the best of our knowledge, this is the first study to evaluate predictors of prehospital delay in iran in a large population of stemi patients undergoing p-pci. in the current study, using multivariate analysis, pain to door time was found to be significantly higher in female gender, uneducated patients, those with onset of chest pain between 00:00 to 6:00 or 7:00 to 12:00, self-transported patients or individuals who were referred from other hospitals, patients with atypical chest pain this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. poorhosseini et al. 4 table 2: past medical history of the patients variables number (%) prehospital delay (minute) p median iqr 25% 75% diabetes mellitus yes 657 (31.2) 309.50 123.25 629.25 0.029 no 1446 (68.8) 264.00 115.25 628.00 hypertension yes 852 (40.5) 315.50 130.75 670.00 0.004 no 1251 (59.5) 250.00 110.00 596.25 hyperlipidemia yes 880 (41.8) 266.50 116.25 612.00 0.383 no 1223 (58.2) 285.50 120.00 640.25 smoking yes 739 (35.1) 252.00 111.50 612.00 0.235 no 1364 (64.9) 290.00 120.00 649.00 opium abuse yes 303 (14.4) 340.00 133.00 663.00 0.081 no 1800 (85.6) 270.00 117.00 618.00 family history of cad yes 354 (16.8) 253.00 102.00 607.50 0.066 no 1749 (83.2) 285.00 120.00 642.00 cerebrovascular event yes 78 (3.7) 266.00 111.00 547.50 0.852 no 2025 (96.3) 279.00 120.00 630.00 chronic kidney disease yes 46 (2.2) 350.50 157.00 679.50 0.324 no 2057 (97.8) 274.00 119.75 627.75 history of cabg yes 77 (3.7) 191.00 97.50 425.50 0.085 no 2026 (96.3) 280.00 120.00 630.00 history of myocardial infarction yes 153 (7.3) 330.00 125.00 890.00 0.053 no 1950 (92.7) 270.00 119.00 610.00 history of coronary stenting yes 122 (5.8) 266.00 110.00 733.75 0.924 no 1981 (94.2) 279.50 120.00 621.25 infarct related artery lad 1144 (54.4) 270.00 120.00 642.50 0.621 lcx 297 (14.1) 310.00 119.25 583.25 rca 612 (29.1) 287.00 120.00 645.75 svg 50 (2.4) 162.00 98.75 898.00 hx, history; cad, coronary artery disease; cabg, coronary artery bypass graft; lad, left anterior descending; lcx, left circumflex; rca, right coronary artery; svg, saphenous vein graft. and history of hypertension and opium abuse; while history of cabg was associated with shorter pain to door time. in a study by noorani et al. (15), prehospital delay has been shown to be associated with long distance from hospital, lower socioeconomic status and using ambulance. in a study by moser el al. (11) several factors have been mentioned to be associated with prehospital delay including female gender, older age, worse socioeconomic status, history of angina, having cardiovascular risk factors and poor knowledge of the individual. in the current study we found that patients with chest pain between 00:00 to 6:00 or 7:00 to 12:00 had higher prehospital delays. on the contrary, patients transferred by ems and educated individuals had lower pain to door time. infarct related artery had no significant effect in pain to door time in our study population. our findings are in line with those of peng et al. (16) who assessed 1088 stemi patients. they demonstrated that prehospital delay was negatively correlated with high educational level, previous history of mi, transportation by ambulance, onset of pain during the daytime (6:00-18:00) and anterior and posterior mi. in our study, the level of education was negatively correlated with pain to door time. similar to our work, the study of heo et al. (17), reported a pain to door time of 144, 76 and 68 minutes in stemi patients with low, moderate and high educathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e29 table 3: index event’s characteristics index number prehospital delay (minute) p median iqr 25% 75% mode of transfer ambulance 196 (9.3) 209.00 91.25 458.00 self-transport 1808 (86.8) 280.00 120.00 650.00 <0.001 referral 99 (4.7) 364.00 208.50 684.00 pain onset time 0 to 6 554 (26.4) 345.00 112.00 872.00 <0.001 7 to 12 617 (29.4) 324.00 135.00 677.50 13 to 18 519 (24.7) 264.00 120.00 462.00 19 to 24 412 (19.6) 205.00 106.25 549.50 pain description typical chest pain 1984 (94.3) 270.00 117.00 613.00 atypical chest pain 84 (4.0) 488.00 176.00 895.75 0.005 no chest pain 35 (1.7) 307.00 99.00 705.00 pain duration >30 min 1183 (56.3) 300.00 120.00 663.00 0.022 11-30 min 801 (38.1) 248.00 112.50 581.50 1-10 min 84 (4.0) 324.00 142.00 847.00 no chest pain 35 (1.7) 307.00 99.00 705.00 back pain yes 26 (1.2) 377.50 149.25 904.50 0.146 no 2077 (98.8) 275.50 119.00 620.25 epigastric pain yes 277 (13.2) 335.50 144.25 701.75 0.007 no 1826 (86.8) 270.00 115.00 615.00 jaw pain yes 14 (0.7) 221.50 131.25 553.75 0.640 no 2089 (99.3) 278.50 120.00630.00 left precordial pain yes 1022 (48.6) 265.00 113.50 612.00 0.162 no 1081 (51.4) 289.00 120.00 645.00 retro-sternal pain yes 1400 (66.6) 270.00 115.00 630.00 0.223 no 703 (33.4) 285.00 127.50 616.00 right precordial pain yes 11 (0.5) 345.00 205.00 610.00 0.495 no 2092 (99.5) 276.00 119.50 630.00 arm & shoulder pain yes 71 (3.4) 227.50 140.25 574.00 0.815 no 2032 (96.6) 279.50 117.25 630.75 tional levels, respectively. in medea study (18) on 486 acute mi patients, prehospital delay was higher in patients with low mi-knowledge. they also found that patients with atypical symptoms had higher prehospital delays, which corresponds to our findings. our study showed that p2d is still very high in iran and revealed the high-risk groups associated with longer p2d. we assume that effective actions should be implemented to increase the general population’s knowledge about the presentations of acute mi in order to decrease the time to seek treatment. 5. limitations and strengths being single-centered and retrospective design of the current work can be considered as our study limitations. we had missing values in pain or door times in 281 patients and thus we excluded them from the final analysis. we had no information regarding the patients’ place of living and could not retrieve the data on their distance from the hospital. meanwhile, the present study is the largest study that has been done to evaluate p2d in iranian patients and the first study that has published after starting the 24/7 program. unlike ipace2 study, only stemi patients, for whom p2d is applicable and can be defined, were included in our study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. poorhosseini et al. 6 table 4: multivariate analysis for prediction of log (p2d) variable beta coefficient 95% confidence interval p lower upper gender male female 0.064 0.003 0.125 0.038 education university high school diploma 0.070 -0.002 0.143 0.058 elementary education 0.082 -0.025 0.189 0.135 uneducated 0.213 0.115 0.311 <0.001 pain onset time 19 to 24 13 to 18 0.043 -0.030 0.116 0.243 7 to 12 0.119 0.049 0.190 0.001 0 to 6 0.130 0.058 0.202 <0.001 mode of transfer ambulance self-transfer 0.098 0.015 0.181 0.020 referral 0.253 0.117 0.389 <0.001 pain description typical chest pain atypical chest pain 0.170 0.048 0.293 0.006 no chest pain 0.066 -0.121 0.253 0.491 hypertension no yes 0.052 0.002 0.102 0.041 opium no yes 0.076 0.007 0.146 0.031 cabg no yes -0.124 -0.252 -0.004 0.048 cabg: coronary artery bypass graft. table 5: median of prehospital delay in st-elevation myocardial infarction patients in various countries according to published reports country prehospital delay (minute) year united stated (10, 19) 290 1990 84 in males 2002 121 in females 59 in males 2006 81 in females denmark (20) 125 1998 australia and new zealand (21) 145 2008 south korea (22) 130 2012 india (23, 24) 310 2003 290 2016 6. conclusion in the present study female gender, transfer via vehicles other than ambulance, atypical chest pain, low level of education, late night and morning onset of pain, history of hypertension and opium abuse were associated with higher prehospital delay while history of cabg was associated with shortened p2d. 7. appendix 7.1. acknowledgements the present work was supported by tehran heart center, tehran university of medical sciences. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e29 table 6: iranian studies on prehospital delay study year city number* acs forms p2d momeni (25) 2011 rasht 162 stemi 120 khosravi (26) 2011 isfahan 103 stemi 255 farshidi (27) 2012 hormozgan 227 stemi & nstemi n/a ipace2 (28) 2012 tehran, mashhad, isfahan, shiraz, tabriz 1997 ua & nstemi & stemi 265 taghadosi (29) 2013 kashan 117 stemi & nstemi 129 *: number of patients, p2d: pain to door time (minutes), acs: acute coronary syndrome. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids hamidreza poorhosseini: 0000-0002-5733-9588 mohammad saadat: 0000-0003-4950-8334 mojtaba salarifar: 0000-0001-9062-3495 seyedeh hamideh mortazavi: 0000-0002-8167-2241 babak geraiely: 0000-0001-6695-7751 7.3. funding/support none. 7.4. conflict of interest none. references 1. murray cj, vos t, lozano r, et al. disability-adjusted life years (dalys) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. the lancet. 2013;380(9859):2197223. 2. finegold ja, asaria p, francis dp. mortality from ischaemic heart disease by country, region, and age: statistics from world health organisation and united nations. int j cardiol. 2013;168(2):934-45. 3. mendis s. global progress in prevention of cardiovascular disease. cardiovasc diagn ther. 2017;7(suppl 1):s32s8. 4. avorn j, knight e, ganz da, schneeweiss s. therapeutic delay and reduced functional status six months after thrombolysis for acute myocardial infarction. the american journal of cardiology. 2004;94(4):415-20. 5. cullen l, greenslade jh, menzies l, et al. time to presentation and 12-month health outcomes in patients presenting to the emergency department with symptoms of possible acute coronary syndrome. emergency medicine journal. 2016;33(6):390-5. 6. nilsson g, mooe t, soderstrom l, samuelsson e. prehospital delay in patients with first time myocardial infarction: an observational study in a northern swedish population. bmc cardiovascular disorders. 2016;16(1):93. 7. de luca g, suryapranata h, ottervanger jp, antman em. time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. circulation. 2004;109(10):1223-5. 8. akimbaeva z, ismailov z, akanov aa, radisauskas r, padaiga z. assessment of coronary care management and hospital mortality from st-segment elevation myocardial infarction in the kazakhstan population: data from 2012 to 2015. medicina (kaunas). 2017;53(1):58-65. 9. beig jr, tramboo na, kumar k, et al. components and determinants of therapeutic delay in patients with acute st-elevation myocardial infarction: a tertiary care hospital-based study. j saudi heart assoc. 2017;29(1):714. 10. kaul p, armstrong pw, sookram s, leung bk, brass n, welsh rc. temporal trends in patient and treatment delay among men and women presenting with st-elevation myocardial infarction. am heart j. 2011;161(1):91-7. 11. moser dk, kimble lp, alberts mj, et al. reducing delay in seeking treatment by patients with acute coronary syndrome and stroke: a scientific statement from the american heart association council on cardiovascular nursing and stroke council. circulation. 2006;114(2):168-82. 12. salarifar m, askari j, saadat m, et al. strategies to reduce the door-to-device time in st-elevation myocardial infarction patients. the journal of tehran university heart center. 2019;14(1):18-27. 13. poorhosseini h, abbasi sh. the tehran heart center. eur heart j. 2018;39(29):2695-6. 14. salarifar m, mousavi mr, saroukhani s, et al. percutaneous coronary intervention to treat chronic total occlusion: predictors of technical success and one-year clinical outcome. tex heart inst j. 2014;41(1):40-7. 15. noorani f, runge m, tripathi s, et al. pre-hospital delays in care for stemi patients in mumbai: challenges and opportunities. am heart assoc; 2016. 16. peng yg, feng jj, guo lf, et al. factors associated with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. poorhosseini et al. 8 prehospital delay in patients with st-segment elevation acute myocardial infarction in china. am j emerg med. 2014;32(4):349-55. 17. heo jy, hong kj, shin sd, song kj, ro ys. association of educational level with delay of prehospital care before reperfusion in stemi. am j emerg med. 2015;33(12):1760-9. 18. albarqouni l, smenes k, meinertz t, et al. patients’ knowledge about symptoms and adequate behaviour during acute myocardial infarction and its impact on delay time: findings from the multicentre medea study. patient educ couns. 2016;99(11):1845-51. 19. yarzebski j, goldberg rj, gore jm, alpert js. temporal trends and factors associated with extent of delay to hospital arrival in patients with acute myocardial infarction: the worcester heart attack study. american heart journal. 1994;128(2):255-63. 20. rasmussen ch, munck a, kragstrup j, haghfelt t. patient delay from onset of chest pain suggesting acute coronary syndrome to hospital admission. scand cardiovasc j. 2003;37(4):183-6. 21. mckinley s, aitken lm, marshall ap, et al. delays in presentation with acute coronary syndrome in people with coronary artery disease in australia and new zealand. emerg med australas. 2011;23(2):153-61. 22. lee mr, yun kh, kim dh, et al. factors related to prehospital delay in korean patients with st-segment elevation myocardial infarction: a data from the province of jeonbuk regional cardiovascular center. journal of lipid and atherosclerosis. 2016;5(1):21-6. 23. malhotra s, gupta m, chandra kk, grover a, pandhi p. prehospital delay in patients hospitalized with acute myocardial infarction in the emergency unit of a north indian tertiary care hospital. indian heart j. 2003;55(4):34953. 24. george l, ramamoorthy l, satheesh s, saya rp, subrahmanyam dk. prehospital delay and time to reperfusion therapy in st elevation myocardial infarction. j emerg trauma shock. 2017;10(2):64-9. 25. momeni m, salari a, shafighnia s, ghanbari a, mirbolouk f. factors influencing pre-hospital delay among patients with acute myocardial infarction in iran. chin med j. 2012;125(19):3404-9. 26. khosravi ar, hoseinabadi m, pourmoghaddas m, et al. primary percutaneous coronary intervention in the isfahan province, iran; a situation analysis and needs assessment. arya atheroscler. 2013;9(1):38-44. 27. taghaddosi m, dianati m, fath gharib bidgoli j, bahonaran j. delay and its related factors in seeking treatment in patients with acute myocardial infarction. arya atheroscler. 2010;6(1):35-41. 28. kassaian se, masoudkabir f, sezavar h, et al. clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in iran: the iranian project for assessment of coronary events 2 (ipace2). bmj open. 2015;5(12):e007786. 29. farshidi h, rahimi s, abdi a, salehi s, madani a. factors associated with pre-hospital delay in patients with acute myocardial infarction. iran red crescent med j. 2013;15(4):312-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations and strengths conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e8 or i g i n a l re s e a rc h the effects of open and closed suction methods on occurrence of ventilator associated pneumonia; a comparative study seyed hossein ardehali1, alireza fatemi2∗, seyedeh fariba rezaei2, mohammad mehdi forouzanfar3, zahra zolghadr4 1. department of anesthesiology & critical care, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 4. department of biostatistics, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. received: october 2019; accepted: december 2019; published online: 11 january 2020 abstract: introduction: endotracheal suctioning is a method commonly used to clean airway secretions in patients under mechanical ventilation (mv ). this study aimed to compare the effects of open and closed suction methods on the occurrence of ventilator associated pneumonia (vap). methods: this comparative study was carried out on adult intensive care unit (icu) patients in need of mv for more than 48 hours, from october 2018 to january 2019. patients were randomly allocated to either closed tracheal suction system (ctss) group or open tracheal suction system (otss) group. patients were monitored for developing vap within 72 hours of intubation and the findings were compared between groups. results: 120 cases with the mean age of 57.91±19.9 years were randomly divided into two groups (56.7% male). the two groups were similar regarding age (p = 0.492) and sex (p = 0.713) distribution. 22 (18.3%) cases developed vap (12 (20%) in osst group and 10 (16.7%) in csst; p = 0.637). the most prevalent bacterial causes of vap were acinetobacter_baumannii (72.7%), klebsiella pneumoniae (18.2%), and methicillin-resistant staphylococcus aureus (9.1%), respectively. there was not any significant difference between groups regarding the mean duration of remaining under mv (p = 0.623), mean duration of hospitalization (p = 0.219), frequency of vap (p = 0.637), and mortality (p = 0.99). conclusion: it seems that type of endotracheal suction system (osst vs. csst) had no effect on occurrence of vap and other outcomes such as duration of need for mv and icu stay as well as mortality. keywords: pneumonia, ventilator-associated; respiration, artificial; critical care; intensive care units; suction cite this article as: ardehali s h, fatemi a, rezaei s f, forouzanfar m m, zolghadr z. the effects of open and closed suction methods on occurrence of ventilator associated pneumonia; a comparative study. arch acad emerg med. 2020; 8(1): e8. 1. introduction ventilator-associated pneumonia (vap) is one of the most common nosocomial infections in intensive care units (icus), and is associated with a high rate of morbidity and high cost of care (1). therefore, any intervention to reduce vap will result in reducing costs, morbidity and mortality (2). endotracheal tube (ett) suctioning is an essential procedure ∗corresponding author: alireza fatemi; men’s health and reproductive health research center, shohadaye tajrish hospital, shahrdary avenue, tajrish square, tehran, iran. phone: 00989128949858, fax: 00982122719014, email: alireza.fatemi.md@gmail.com in patients undergoing mechanical ventilation (mv ) with intubation to keeping the airways open through removal of accumulated pulmonary secretions (3). in addition, performing suction accurately is important to prevent vap (4). two different methods are used for ett suctioning, open tracheal suction system (otss), and closed tracheal suction system (ctss). otss method requires participation of two nurses and may lead to temporary disruption of ventilation and oxygen supply due to disconnection of the patient from ventilation device during suctioning and the most important risk factor in this method is hypoxia (5, 6). however, in ctss method, ett suctioning can be administrated through connections in closed suction set and while the ventilation is bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h. ardehali et al. 2 ing performed without disconnecting the patient from the ventilator (7). the effect of open and closed suction methods on preventing vap is still an open field to be explored, because the results of previous studies are contradictory (8-12). some studies showed that there was no difference between closed and open endotracheal suction systems in terms of vap development (9, 11, 12). on the other hand, alipour et al. (10) and fakhar et al. (13) showed that closed suction is associated with a lower risk of vap compared to open suction. therefore, we conducted this comparative study to compare the effects of open and closed suction methods on vap in mechanically ventilated patients. 2. methods 2.1. study design and setting this comparative study was conducted prospectively on icu-admitted patients in shohadaye tajrish hospital, tehran, iran, from october 2018 to january 2019. patients were randomly divided into two groups of ctss and otss and the outcomes (vap occurrence, mortality, icu stay, and duration of need to mv ) of the two groups were compared. this study was performed after receiving approval from the ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.msp.rec.1398.69). a written consent was obtained from patients or legal guardians of patients. 2.2. participants adult patients who underwent mv for more than 48 hours were included in the study. patients unwilling to participate or those with pneumonia or any other underlying respiratory diseases that increase the risk of pneumonia at the time of admission and patients who had remained intubated for more than 48 hours before admission were excluded from the study. 2.3. data gathering demographic characteristics of patients (age and sex), duration of mv and the length of hospital stay as well as developing vap within 72 hours of intubation were examined and recorded by an intensivist for all cases. 2.4. procedure patients who met the inclusion criteria were randomly divided into two groups of ctss and otss based on endotracheal suction methods using sequential randomization. in both groups, throat samples from endotracheal tubes and ventilator tubing were taken to determine the rate of colonization. conventional bacteriological methods were used for identification of isolated micro-organisms. antimicrobial susceptibility test was performed using disk diffusion method according to clsi (clinical and laboratory standards institute) guidelines (14). suction methods were administrated based on the protocol of american association for respiratory care (aarc) (15). endotracheal suction was performed by experienced icu nurses. in the otss group, suctioning was performed using single use catheters with full barrier measures (hand washing and use of gloves). patients were pre-oxygenated for 2 minutes before suctioning. in the ctss group, the system used for respiratory system suctioning was (vital-cath tm 72 closed suction systems) and suction catheter was changed every 48 hours. similar to the other group, patients were pre-oxygenated, and suctioning was performed without disconnection from the ventilator. the following vap prophylaxis strategies were used in all patients: head elevation (30-40◦), heat and moisture exchanger (hme) for humidification, protocolized sedation and enteral nutrition, performing suction only when necessary, avoiding routine change of the respiratory circuit unless necessary, mouth washing with chlorhexidine in each shift, pantoprazole for prophylaxis of stress ulcer, verification of gastric residual volume in each shift, avoidance of unnecessary extubation or intubation, maintenance of cuff pressure between 20-30 mmhg and continuous aspiration of subglottic secretions. all interventions were done by one medical doctor and two nurses who provided care for both groups. diagnosis of vap was performed based on clinical pulmonary infection score (cpis) (16). patients were monitored for 72 hours from suctioning and examined by an infectious disease specialist. bacterial pneumonia index calculated based on persistent infiltration in the chest x-ray, body temperature, white blood cell count, airway discharges, ratio of arterial blood oxygen to inhaled oxygen, and culture and smear of lung discharges were recorded. patients were considered to have pneumonia if they received a score higher than 6 (appendix 1) (17). 2.5. statistical analysis qualitative variables were reported as percentage and quantitative variables as mean± standard deviation. we used student t test and chi-square test for detection of differences between the two groups. fisher’s exact test was used for qualitative analysis when necessary. for analyzing data, spss version 21 (spss inc., imb corporation, chicago, illinois, usa) was used. p value equal to or less than 0.05 was considered statistically significant. 3. results 120 cases with the mean age of 57.91±19.9 (17 – 94) years were randomly divided into two groups of osst or csst (56.7% male) with equal participants. the two groups were similar regarding age (p = 0.492) and sex (p = 0.713) distrithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e8 table 1: comparing the outcomes between open tracheal suction system (otss) and closed tracheal suction system (ctss) groups outcomes type of suction p otss (n=60) ctss (n=60) ventilator associated pneumonia yes 12 (20.0) 10 (16.7) 0.637 no 48 (80.0) 50 (83.3) duration of ventilation mean ± sd 13.47±10.83 12.62±7.82 0.623 range (days) 5-65 5-47 hospitalization days mean ± sd 21.83±12.72 19.20±10.50 0.219 range (days) 8-73 8-55 microorganism acinetobacter_baumannii 9 (56.2) 7 (43.8) 0.96 klebsiella pneumoniae 2 (50.0) 2 (50.0) mrsa 1 (50.0) 1 (50.0) no 48 (49.0) 50 (51.0) death yes 39 (65.0) 39 (65.0) 0.99 no 21 (35.0) 21 (35.0) data are presented as mean ± standard deviation (sd) or frequency (%). mrsa: methicillin-resistant staphylococcus aureus. appendix 1: clinical pulmonary infection score used for diagnosis of ventilator-associated pneumonia criterion score temperature, ◦c ≥36.5 and ≤38.4 0 38.5 and ≤38.9 1 ≥39 and ≤ 36 2 leukocyte count (/mm3 ) ≥4,000 and ≤11,000 0 <4,000 or >11,000 1 +band forms ≥500 2 oxygenation, pao2 /fio2 >240 or ards 0 ≤240 and no evidence of ards 2 pulmonary radiography no infiltrate 0 diffused (or patchy) infiltrate 1 localized infiltrate 2 culture of tracheal aspirate* pathogenic bacteria cultured ≤1+ or no growth 0 pathogenic bacteria cultured >1+ 1 + same pathogenic bacteria seen on the gram stain >1+ 2 *: semi-quantitative: 0-1-2 or 3+. ards: acute respiratory distress syndrome. bution. 22 (18.3%) cases developed vap (12 (20%) in osst group and 10 (16.7%) in csst; p = 0.637). the most prevalent bacterial causes of vap were acinetobacter_baumannii (72.7%), klebsiella pneumoniae (18.2%), and methicillinresistant staphylococcus aureus (9.1%), respectively. no statistically significant difference was detected between groups regarding the frequency of bacterial causes vap (p = 0.99). table 1 compares the outcomes of patients between groups. there was not any significant difference between groups regarding the mean duration of undergoing mv (p = 0.623), mean duration of hospitalization (p = 0.219), frequency of vap (p = 0.637), and mortality (p = 0.99). 4. discussion the results revealed that the type of endotracheal suction system (osst vs. csst) had no effect on development of vap and icu outcome. in addition, our results did not show any significant difference between the two groups regarding length of icu stay and duration of mv and mortality rate, which is similar to the results of combes et al. (18), topeli et al. (12), ozcan et al. (19) and hamishekar et al. (9). different studies that assessed the effect of open and closed suction on incidence of vap showed controversial findings (9, 10, 12). our finding is consistent with some previous studies that showed no statistically significant difference between osst and csst endotracheal suctioning systems in terms of vap development (20, 21). in a systematic review by subirana et al., 16 clinical trials were assessed; their results showed that using open or closed suction methods had no effect on vap (22). a prospective randomized study, which was carried out on 100 patients in surgical icu by hamishekar et al. to evaluate the effect of ctss versus otss did not show any statistically significant effect on vap incidence in multivariate analysis (9). however, in contrast to our findings, some studies showed that closed suction method has superiority over open method in reducing the incidence of vap (10, 13). in a prospective clinical trial performed by david et this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h. ardehali et al. 4 al. clinical results of osst and csst were assessed in 200 patients under mv in india; they found that using closed suction reduced the incidence of vap. however, mortality rate and hospital stay in icu were the same in both groups (23). the controversial/contradicting results in different studies can have many reasons such as small sample size, inappropriate inclusion or exclusion criteria such as including patients with underlying respiratory diseases, short duration of study period, not teaching the principles of using closed suction to nurses, and not using the vap prophylaxis strategies in open suction method. in the present study, we tried to solve the above-mentioned limitations by using appropriate inclusion and exclusion criteria, including appropriate number of patients in both groups, properly training nurses for using closed suction, and using vap prophylaxis strategies as a health principle. considering that both endotracheal suction systems have advantages and disadvantages, it seems that the incidence of vap can be reduced by using aseptic precautions based on signs and symptoms, as well as the correct use of guidelines in both suction systems. the distribution of micro-organisms causing vap was different in various studies, which could be due to differences in patient demographics, methods of diagnosis, duration of hospitalization, icu stays, and antibiotic policy (24, 25). in the present study, acinetobacter_baumannii was the most common isolated pathogen (72.7%) in patients with vap followed by klebsiella pneumoniae (18.2%) and methicillin-resistant staphylococcus aureus (mrsa) (9.1%). consistent with the present investigation, a study by dey et al. reported acinetobacter species (48.94%) as the most common isolate from early-onset and late-onset vap (26). previous studies have shown that acinetobacter species ranked fifth among the causative organisms of vap (27-29). bozorgmehr et al. reported that acinetobacter baumannii and klebsiella pneumoniae were the most common germs growing in sputum cultures and most of them were pan drug resistance (pdr) or extensive drug resistance (xdr) (30). our study limitation is that type of vap (early or delayed) was not studied, which is suggested to be further evaluated in future studies. in addition, data regarding underlying diseases and cause of intubation were not recorded; however, they may play a role in increasing mortality due to ventilation. in conclusion, according to the findings of this study, the use of csst has no superiority over osst in reducing vap incidence of and it has no effect on icu outcome. the incidence of vap was remarkable in both groups, which led to an increase in hospitalization and mechanical ventilation in these patients. in addition, acinetobacter_baumannii was found to be the most common isolated pathogen followed by k. pneumoniae and mrsa. 5. conclusion it seems that type of endotracheal suctioning system (osst vs. csst) had no effect on occurrence of vap and other outcomes such as duration of mv and icu stay as well as mortality. 6. declarations 6.1. acknowledgements hereby, we thank the icu staff members of shohadaye tajrish hospital for their hearty cooperation and helping us perform this study. 6.2. author contribution all the authors met the 4 criteria recommended by the international committee of medical journal editors for gaining authorship. authors orcids seyed hossein ardehali: 0000-0001-6656-3875 alireza fatemi: 0000-0003-0671-7611 mohammad mehdi forouzanfar: 0000-0003-0626-8545 zahra zolghadr: 0000-0001-6562-0348 6.3. funding/support none. 6.4. conflict of interest all authors declare that they have no conflict of interest. references 1. charles mp, kali a, easow jm, joseph nm, ravishankar m, srinivasan s, et al. ventilator-associated pneumonia. the 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and the world federation of pediatric intensive and critical care societies. 2012;13(1):e25-32. 22. subirana m, sola i, benito s. closed tracheal suction systems versus open tracheal suction systems for mechanically ventilated adult patients. the cochrane database of systematic reviews. 2007(4):cd004581. 23. david d, samuel p, david t, keshava sn, irodi a, peter jv. an open-labelled randomized controlled trial comparing costs and clinical outcomes of open endotracheal suctioning with closed endotracheal suctioning in mechanically ventilated medical intensive care patients. journal of critical care. 2011;26(5):482-8. 24. liu q, yang j, zhang j, zhao f, feng x, wang x, et al. description of clinical characteristics of vap patients in mimic database. frontiers in pharmacology. 2019;10:62. 25. chin t, kushner b. antibiotic utilization patterns in patients with ventilator-associated pneumonia: a canadian context. 2016;2016:3702625. 26. dey a, bairy i. incidence of multidrug-resistant organisms causing ventilator-associated pneumonia in a tertiary care hospital: a nine months’ prospective study. annals of thoracic medicine. 2007;2(2):52-7. 27. giamarellou h, antoniadou a, kanellakopoulou k. acinetobacter baumannii: a universal threat to public health? international journal of antimicrobial agents. 2008;32(2):106-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h. ardehali et al. 6 28. joly-guillou ml. clinical impact and pathogenicity of acinetobacter. clinical microbiology and infection : the official publication of the european society of clinical microbiology and infectious diseases. 2005;11(11):86873. 29. peleg ay, seifert h, paterson dl. acinetobacter baumannii: emergence of a successful pathogen. clinical microbiology reviews. 2008;21(3):538-82. 30. bozorgmehr r, bahrani v, fatemi a. ventilatorassociated pneumonia and its responsible germs; an epidemiological study. emergency. 2017; 5(1): e26. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e47 or i g i n a l re s e a rc h epidemiologic characteristics of patients admitted to emergency department with dermatological complaints; a retrospective cross sectional study deniz kilic1, ozlem yigit2∗, taylan kilic3, cagri sefa buyurgan4, ozlem dicle5 1. department of emergency medicine, kepez state hospital, antalya, turkey. 2. department of emergency medicine, faculty of medicine, akdeniz university, antalya, turkey. 3. department of emergency medicine, antalya education and research hospital, antalya, turkey. 4. department of emergency medicine, omer halisdemir university education and research hospital, nigde, turkey. 5. department of dermatology, faculty of medicine, akdeniz university, antalya, turkey. received: june 2019; accepted: july 2019; published online: 19 august 2019 abstract: introduction: dermatological diseases constitute 5-8% of all emergency department (ed) visits. however, little is known about these patients. the aim of this study is to determine the epidemiologic characteristics of patients admitted to ed with dermatological complaints. methods: this is a retrospective cross-sectional study conducted in the ed of a university hospital. patients over 18 years of age who presented to ed with the following complaints were included in the study: rash, pruritus, and edema sensation in the throat or shortness of breath due to an allergic reaction. demographics, chief complaints, final diagnoses, triage categories, consultations and hospitalization rates were obtained through computerized database of the hospital. results: 859 patients were included in the final analysis. 511 (59.5%) patients were female and the mean age of patients was 39.03±15 years. the most common complaint and final diagnosis were skin rash with pruritus (50.9%) and urticaria with drug eruptions (84.5%), respectively. two patients (0.2%) had an emergent triage category. 804 (93.6%) patients were discharged from ed, while 55 (6.4%) received consultations, resulting in 19 (34.5%) hospitalizations. conclusion: most of the patients admitted to ed with dermatological complaints are non-urgent and can be treated as outpatients. however, physicians should be alert for emergent causes, as well. keywords: emergency medicine; urticaria; referral and consultation; exanthema; anaphylaxis cite this article as: kilic d, yigit o, kilic t, buyurgan c s, dicle o. epidemiologic characteristics of patients admitted to emergency department with dermatological complaints; a retrospective cross sectional study. arch acad emerg med. 2019; 7(1): e47. 1. introduction although dermatology is often thought of as a non-acute and outpatient centered clinic, it has been reported that approximately 4-12% of all emergency department (ed) visits are due to skin complaints (1). many of these skin lesions are caused by infections, irritants and allergens (2). most of the dermatological lesions presenting to the eds are neither serious nor life-threatening. however, patients usually seek immediate attention and keep on crowding the ed with non∗corresponding author: ozlem yigit; department of emergency medicine, faculty of medicine,akdeniz university, dumlupinar bulvari, antalya, turkey. e-mail: ozlemyigit@akdeniz.edu.tr, tel: +90505 644 42 86 urgent complaints. dermatological emergencies involve less severe or life-threatening diseases such as infectious skin diseases (e.g. abscesses, cellulitis and necrotizing fasciitis), acute rashes, severe cutaneous adverse reactions (e.g. drug rash with eosinophilia and systemic symptoms (dress) syndrome, stevens johnson syndrome (sjs), and toxic epidermal necrolysis (ten)), erythroderma, vasculitis, flares of chronic inflammatory skin diseases, urticaria, and angio-edema (3). it is important for an emergency physician (ep) to recognize and treat dermatological emergencies, as some of these conditions can acutely evolve and become lethal if the diagnosis is not made early in the disease course and the appropriate treatment is not provided in time (4). relieving the patient’s complaints, prescribing appropriate treatment, and recommending outpatient control visits to the dermatology clinics this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. kilic et al. 2 for nonurgent diseases are the other important responsibilities for the eps. there are few studies documenting patients’ characteristics and ed consultations. therefore, the aim of this study is to describe the epidemiological characteristics of the patients admitted to the ed with a dermatologic complaint. as a secondary aim, we sought to get epidemiological data about our population and use these data for planning the content of our emergency residency program about the most common dermatological diseases. 2. methods 2.1. study design and setting this was a retrospective cross-sectional study conducted in the ed of a university hospital with an annual turnover of approximately 100,000 adult patients. the study was approved by the local ethical committee (code: 18/05/2016–288; from akdeniz university 2012-kaek-20). patients who were over 18 years old and admitted to the ed with a dermatological complaint during a 6-month period were included in the study. pruritus, rash, erythema, and swelling in the throat and dyspnea due to an allergic reaction were presumed to be the major complaints that could be seen in the ed. the resident eps were asked which international code of disease-10 (icd-10) codes they were using for recording the patients with dermatological complaints. the codes identified after this preliminary questionnaire were searched in the electronic database of the hospital. the identified icd-10 codes were l29 (pruritus, unspecified), l50 (urticaria), l50.8 (other: chronic urticaria), l50.9 (urticaria, unspecified), r21 (rash and other nonspecific skin eruption), t78.2 (anaphylactic shock), t78.3 (angioneurotic edema), and t78.4 (other and unspecified allergy). patients’ demographics and complaints, final diagnoses, triage categories, time of the ed admissions, consultations, discharge and hospitalization rates, and control visits to the outpatient dermatology clinics of the hospital after discharge from the ed were searched and recorded in the study form. 2.2. participants since ed admissions of the children were carried out in the pediatric ed of the hospital, patients under the age of 18 were excluded from the study. patients who had revisited the ed within five days were also excluded due to their ongoing treatment. also, when icd-10 codes were asked from resident eps, it was learned that they were using icd-10 codes of l03 (cellulitis) and other infectious skin disorders in different manners. in case of a necessity to make a laboratory testing for differential diagnosis between infectious and noninfectious causes or to prescribe an antibiotic even for prophylactic purposes, an icd code of an infectious cause must be registered into the electronic database of the patient to cover the health insurance payment system. the retrospective design of the study had made it difficult to differentiate between mannered and actual diagnoses. therefore, cellulitis and other infectious skin disorders were not included in the study. 2.3. data collection the demographics of the patients, admission complaints, time of the ed admissions (hours in a day and month), triage categories, referral from other hospital, consultations, and discharge and hospitalization ratios were recorded in the study form. revisit to the ed within five days after discharge and the control visits to the dermatology clinic were also recorded. admission complaints were classified as; pruritus, rash, itchy erythematous skin rash, insect bite, and edema sensation in the throat and dyspnea due to an allergic reaction. ed admission time was classified as; 08:00-16:59 daytime, 17:00-23:59 evening, and 00:00-07:59 night. triage categories were classified as green (non-urgent), yellow (urgentdelayed), and red (emergent). due to the inability to differentiate between urticaria and drug eruptions, these final diagnoses were combined as a single diagnosis as urticaria and drug eruptions. similarly, a combination was also made for angioedema and anaphylaxis, as well. 2.4. statistical analysis data were analyzed with the ibm spss 20.0 statistical package program. continuous data are presented as mean± standard deviation (sd), and categorical data as frequencies and percentages. univariate analyses between two groups for categorical data were performed using the chi-squared test. a two-sided p value of <0.05 was considered as statistically significant. 3. results 3.1. baseline characteristics of studied patients during the study period, 50622 patients were admitted to the ed. 958 (1.89%) of these patients had dermatologic complaints. after the exclusion of 99 patients, 859 patients were included in the final analysis. patient flow-chart is depicted in figure 1. the mean age was 39.03±15 (18-89) years and 511 (59.5%) patients were female. the most common dermatological complaint was erythematous skin rash with pruritus (%50.9). also, most of the patients had presented to the ed between 08:00-16:59 hours in the daytime (45.9%) and were in a triage category of yellow (%98.8). patients’ characteristics are depicted in table 1. the most common final diagnosis was urticaria and drug eruptions (84.5%). most of the patients were admitted to the ed between 08:00-16:59 hours (%45.9) and, most of the conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e47 table 1: baseline characteristics of studied patients characteristics number (%) age (years) mean ± sd 39.03±15.03 gender male 348 (40.5) female 511 (59.9) admission complaints itchy and erythematous skin rash 437 (50.9) other rashes 145 (16.9) angioedema and/or difficulty in breathing 129 (15.0) insect bite 21 (2.4) triage category non-urgent 9 (1.0) urgent 848 (98.8) emergent 2 (0.2) time of admission (hours) 08:00-16:59 394 (45.9) 17:00-23:59 312 (36.3) 00:00-07:59 153 (17.8) final diagnosis urticaria and drug eruptions 726 (%84.5) angioedema and anaphylaxis 124 (%14.4) puppp 6 (%0.7) other (dress, sjs) 3 (%0.3) total 859 (%100) puppp: pruritic urticarial papules and plaques of pregnancy, sjs: stevens–johnson syndrome, dress: drug rash with eosinophilia and systemic symptoms. sultations took place in 08:00-16:59 (%43) and 17:00-23:59 (%43) time intervals. time distribution of ed admissions and consultation in a day is depicted in figure 2. when looking at a monthly basis, most of the patients were admitted in hot months (may: 20.8%, june: 17.7%) (figure 3). while 804 (93.6%) patients were discharged with prescriptions to home without any consultations, 55 (6.4%) patients received consultations from other clinics (dermatology, allergy-immunology or ear-nose-throat departments). of these, 19 patients (2.2% of the study population and 34.5% of the consulted patients) were hospitalized in the related clinics. 58 (6.8%) patients were referred from another hospital. these patients had statistically and significantly higher consultation (p=0.002) and hospitalization (p=0.034) rates than the others. 3.2. outcomes it has been shown that, patients with the final diagnosis of angioedema and anaphylaxis have significantly higher consultation (p=0.025) and hospitalization (p=0.004) rates than the urticaria patients. among the patients who were discharged from ed with prescription and instructions, only 122 (15.2%) patients visited the outpatient dermatology clinic of our hospital for control visits. the rate of control visits to the figure 1: patients flow chart. ed: emergency department, n: number. figure 2: distribution of emergency department (ed) admissions and consultations during a day. figure 3: number of the emergency department admissions of patients with dermatological complaint in months. outpatient dermatology clinic was also significantly higher in patients who were consulted during the ed process (27.3% vs 15.2%, p=0.018). a total of 55 patients had revisited the ed within five days after discharge from the ed. while 46 patients had only one revisit, seven patients had two, one patient had three and another patient had four revisits to the ed. there wasn’t any statistically significant difference between the consultation rates of the patients with revisits to the ed and the patients without revisits (9.1% and 6.2%, respectively, p=0.389). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. kilic et al. 4 4. discussion our study shows that the most common dermatological complaint was erythematous skin rash with pruritus and the most common final diagnosis was urticaria. patients presented to emergency department in day-time and many of them were not in a life-threatening situation or urgency. also the rate of control visits to the outpatient dermatology clinic was very low. urticaria-angioedema, sjs, ten, necrotizing fasciitis, and erythroderma are the dermatologic emergencies that can be life-threatening (3). other dermatologic complaints, which can be classified as non-urgent are frequently encountered in the ed. in different reports, the rate of dermatological complaints in all admissions to the ed was reported to be 2.5-8% (5-9). the ratio in our study was found to be 1.89% and it was lower than the previous reports. the infectious diseases, which were not included in our study, like cellulitis or others may be the cause of this lower rate. the predominance of women in our study was similar with the previous reports. we have found a male/female ratio of 0.68. this ratio was 0.85 and 0.71 in the studies by rubegni et al. and grillo et al., respectively (6, 7). in most other studies, this finding was explained by the greater concern among women over skin diseases. while the average age in our study was similar with a previous report from our country (10), it was younger than the other reports from italy and spain (7, 11). the reason for this difference may be that we have a younger population than europe. in the previous studies the mean number of visits was significantly higher and more common during the summer months compared to other months (3, 8, 11). the visits were more frequent in may and june in our study; however, the difference was not statistically significant. most of the patients were admitted to the ed between 8:0016:59 in the daytime. both family physicians’ primary care offices and dermatology clinics were open and available in this time frame. the question “why people with non-urgent complaints visited the ed instead of getting an appointment from a specialist working at outpatient clinics?” used to be a curiosity and has been asked by several researchers in the past. as an answer to this question, a report from france has revealed the following results: even though all patients had known that their situation had not been an emergency, yet concern about pain, discomfort or the course of their diseases had made them visit the ed. they had thought that they could not get a scheduled outpatient clinic appointment within a short time and had not wanted to wait a long time. patients with multiple and various complaints had not wanted to program a few different outpatient clinic appointments and had preferred to use the ed clinics, in their words “where everything is gathered in one place and the doctors work fast” (12). despite the high prevalence of dermatoses in our population, it is difficult to obtain a timely dermatology appointment in our country, the same as many other countries. the mean waiting time for an appointment to the outpatient dermatology clinic ranges between approximately one week and three months. at public hospitals, waiting times are significantly longer as higher percentage of the patients with limited or no health insurance get service from these hospitals. it was, also, shown that dermatological primary diagnosis was more likely in lower-income and underinsured groups (13). underinsured patients face higher rejection rates and longer waiting times for an appointment at outpatient dermatology clinics. thus, these patients may increase the inappropriate use of the eds for non-urgent dermatologic complaints. since our study was in a retrospective design, we were not able to evaluate the insurance and income status of the study population. another possible explanation for the inappropriate use of the ed by young people could be the precarious nature of their working hours, which would prevent them from seeking medical care during the working days (3, 14). in our study, 36.3% of patients were admitted to ed between 17:00-23:59 hours. the patient number decreased between 00:00-07:59 at night, as expected. it might be thought that only really urgent cases may present during these hours. however, on the contrary, the consultation and hospitalization rates did not get any higher in this time interval. the lower ratio of real emergencies (red triage category) in our study, also, supports the argument that the patients use the ed inappropriately. the hospitalization rate of our study was 2%. this result was similar with the previous reports (6, 7). the ratio of hospitalization for the patients who were consulted in the ed was 34.5%. in a previous report, only 18% of consulted patients were hospitalized and the majority (82%) of these consultations were non-urgent (15). in a study performed at a tertiary care center in india, gupta et al. reported that 21 of 100 emergency outpatient consultations qualified as “true dermatologic emergencies” (16). longer waiting time for outpatient care was proposed as a reason for non-urgent consultations by the doctors consulting the patients. this was also a reason for revisits to the ed, so the eps preferred to consult these patients to prevent revisits to the ed. the consultation rate for revisit patients in our study was not statistically different from the patients who did not revisit the ed. patients with a final diagnosis of anaphylaxis and angioedema had significantly higher rates of consultation and hospitalization than those with a final diagnosis of urticaria. this was also pertinent to the patients who were referred from another hospital to our ed, as well. since our clinic is a tertiary care facility, more complicated patients were referred to our hospital. this may explain the higher hospitalization rate in our study. as in the previous reports, the most frequent group of disease this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e47 was urticaria and drug eruptions (5-10, 17, 18). the most significant difference in our study was the final diagnosis for the infectious diseases and dermatoses. we have excluded the skin infections from the study due to the reasons explained before. however, absence of any dermatitis or eczema in the final diagnoses was problematic. since the study had a retrospective design, we selected the patients with the icd-10 codes, which we identified with a preliminary questionnaire before the study. the lack of codes for dermatoses among the most frequently used icd-10 codes might have led to the inability to distinguish these patients in the study. the absence of these final diagnoses might be due to diagnostic icd-10 codes being recorded to the electronic database of the hospital were either a nonspecific complaint code or an incorrect infectious disease code. therefore, either way, it is more likely for dermatoses to be excluded from the study population than these cases never visiting the ed. of all the patients who were discharged from ed with prescription and instructions, only a few patients visited the dermatology outpatient clinic for control examinations, and the remaining 84.8% were only seen by an ep. dermatology is a specialty in its own right and it is unlikely that the ep will approach the patient from a dermatologist’s point of view. however, the ep is obliged to recognize and treat dermatological emergencies. in addition, it is also true that a substantial part of patients with non-urgent dermatological complaints visit the ed instead of outpatient clinics for various reasons. this is not only a problem in our country, but also in the health services of the entire world. a number of studies have been conducted in order to canalize non-emergent patients to the outpatient clinics rather than ed, and policies are being implemented according to the results. however, since the social norms are difficult to change, these policies will not show a positive impact in the near future. in this case, it is inevitable that the ep should have the knowledge to identify the most common dermatologic diseases other than the dermatological pathologies that should be urgent or emergent and manage their treatment. therefore, identification of common dermatological complaints and related diagnoses and shaping the ed residency training program according to the results is essential. taking into consideration the results of our study, it may be suggested that giving more emphasis to the curriculum of our country, especially those related to urticaria and drug eruption, would be beneficial both for the education of eps and patient care. unlike other studies, the fact that no dermatoses were found in our study suggests that physicians have difficulties in recognizing this diagnosis and complementary trainings may also be useful in these situations. selecting common visual dermatological lesions and presenting them to the residents at the weekly clinical session for discussion of the diagnosis, treatment, and outcome may be a practical learning method. 5. limitation we have some limitations. most importantly, this was a retrospective study and the data was gathered through the patients’ files, thus limiting its efficacy. our study covers a period of six months. this makes it difficult to make clear a comment on the distribution of complaints and final diagnoses on a monthly and seasonal basis. this might, also, have created a bias for some diseases such as being in the favor of insect bites. also, there were no clear explanations about drug eruptions in the patient files. therefore, we combined two distinct final diagnoses of urticaria and drug eruption into a unique final diagnosis as urticaria and drug eruption. the same was also done for angioedema and anaphylaxis diagnoses. patients with other dermatologic diagnoses recorded with different codes may have been excluded from the study, as the study population was generated through the complaints and the commonly used icd-10 codes determined by common usage of the resident eps before the study. exclusion of the cellulitis and other infectious causes was, also, a major limitation. a prospective design and at least one year of follow up survey can overcome these limitations. 6. conclusion since most of the patients presenting to ed with dermatological complaints are non-urgent and can be treated as outpatients, eps should have the knowledge to identify the most common dermatologic diseases other than the dermatological pathologies that should be urgent or emergent and manage their treatment. therefore, identification of common dermatological complaints and related diagnoses and shaping the ed residency training program according to the results is essential. 7. appendix 7.1. acknowledgements none. 7.2. authors’ contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors orcids deniz kilic: 0000-0002-4329-9036 ozlem yigit: 0000-0002-3703-7590 taylan kilic: 0000-0003-1638-884x cagri sefa buyurgan: 0000-0001-8662-0670 ozlem dicle: 0000-0001-6022-7221 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. kilic et al. 6 7.3. funding/support none. 7.4. conflict of interest none. references 1. cydulka rk gb. dermatological presentations. . in: john a. marx m, editor. rosen’s emergency medicine: concepts and clinical practice 7nd ed. 7nd ed. philadelphia: mosby elsevier; 2010. p. 1529. 2. feldman sr fa, mcconnell rc. most common dermatologic problems identified by internists, 1990-1994. arch intern med 1998;158(7):726-30. 3. isnard c i-h-os, fardet l, matteodo e, duval s, hemery f. dermatological emergencies: evolution from 2008 to 2014 and perspectives. j eur acad dermatol venereol. 2016;31(2):274-9. 4. frances rodriguez l l-sm. las urgencias en dermatologia. actas dermosifiliogr. 2015;106(4):322-3. 5. martinez-martinez ml e-te, rodriguez-vazquez m, azana-defez jm, martin de hijas-santos mc, juanperez-garcia l. dermatology consultations in an emergency department prior to establishment of emergency dermatology cover. actas dermosifiliogr. 2011;102(1):3947. 6. rubegni p cg, lamberti a, bruni f, tiezzi r, verzuri a. dermatological conditions presenting at the emergency department in siena university hospital from 2006 to 2011. j eur acad dermatol venereol 2015;29(1):164-8. 7. grillo e ea. urgencias dermatologicas: analisis descriptivo de 861 pacientes en un hospital terciariodermatologic emergencies: descriptive analysis of 861 patients in a tertiary care teaching hospital. actas dermosifiliogr. 2013;104(4):316-24. 8. kim jy ch, hong js, jin sp, park hs, lee jh. skin conditions presenting in emergency room in korea: an eightyear retrospective analysis. j eur acad dermatol venereol 2012;27(4):479-85. 9. bancalari-diaz d g-ml, canueto j, andres-ramos i, fernandez-lopez e, roman-curto c. dermatologic emergencies in a tertiary hospital: a descriptive study. actas dermo-sifiliograficas (english edition). 2016;107(8):666-73. 10. dertlioglu sm cd, bozdemir mn. evaluation of dermatological disorders in firat university emergency department. j kartal tr. 2010;12(2):84-8. 11. drago f gg, signori a, campisi c, cozzani e, parodi a. dermatological consultations in an observation unit of an emergency department in italy. j eur acad dermatol venereol. 2015;29(5):973-80. 12. durand ac ps, tanti-hardouin n, gerbeaux p, sambuc r, gentile s. nonurgent patients in emergency departments: rational or irresponsible consumers? perceptions of professionals and patients. bmc res notes. 2012;25(5):525. 13. chen cl fl, kamel h. who uses the emergency department for dermatologic care? a statewide analysis. j am acad dermatol. 2014;71(2):308-13. 14. legoupil d da-c, karam a, peu duvallon p, dupre d, greco m. assessment of dermatological emergencies in a french university hospital. ann dermatol venereol. 2005;132(11 pt 1):857-9. 15. jack ar sa, nichols bj, chong s, williams dt, swadron sp. cutaneous conditions leading to dermatology consultations in the emergency department. west j emerg med. 2011;12(4):551-5. 16. gupta s sk, kumar b. evaluation of emergency dermatological consultations in a tertiary care centre in north india. j eur acad dermatol venereol. 2003;17(3):303-5. 17. murr d bh, bachot n, bagot m, revuz j, roujeau jc. medical activity in a emergency outpatient department dermatology. ann dermatol venereol. 2003;130(2 pt 1):167-70. 18. kiellberg larsen h sc. referral pattern of skin diseases in an acute outpatient dermatological clinic in copenhagen. acta derm venereol. 2005;85(6):509-11. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e5 rev i ew art i c l e applications of end-tidal carbon dioxide (etco2) monitoring in emergency department; a narrative review hamed aminiahidashti1, sajad shafiee2, alieh zamani kiasari3∗, mohammad sazgar1 1. department of emergency medicine, mazandaran university of medical sciences, sari, iran. 2. department of neurosurgery, mazandaran university of medical sciences, sari, iran. 3. departments of anesthesiology and critical care, mazandaran university of medical sciences, sari, iran. received: november 2017; accepted: december 2017; published online: 15 january 2018 abstract: capnograph is an indispensable tool for monitoring metabolic and respiratory function. in this study, the aim was to review the applications of end-tidal carbon dioxide (etco2) monitoring in emergency department, multiple databases were comprehensively searched with combination of following keywords: “etco2”, “emergency department monitoring”, and “critical monitoring” in pubmed, google scholar, scopus, index copernicus, ebsco and cochrane database. keywords: capnography; emergency service, hospital; exhalation; carbon dioxide; monitoring, physiologic © copyright (2018) shahid beheshti university of medical sciences cite this article as: aminiahidashti h, shafiee s, zamani kiasari a, sazgar m. applications of end-tidal carbon dioxide (etco2 ) monitoring in emergency department; a narrative review. 2018; 6(1): e5. 1. introduction c apnometry, measuring the concentration of carbon dioxide (co2) in the atmosphere, was used for the first time during world war ii as a tool for monitoring the internal environment (1). it was used in medicine for the first time in 1950 to measure the amount of co2 exhaled during anesthesia. however, it was not used in practice until the early 1980s and with development of smaller machines, capnometry officially entered the anesthesia field (2, 3). there are two types of capnograph, “side stream” and “mainstream” (4) . in the “mainstream” technique, sampling window is in the ventilator circuit and measures co2, while in the “side stream”, the gas analyzer is located out of the ventilator circuit. in both types, gas analyzer uses infrared radiation, mass or raman spectra and a photo acoustic spectra technology (1, 4). flow measurement equipment is used in volumetric capnograph. colorimetric co2 detector is an example of mainstream form. these devices have a ph sensitive indicator, which changes color in inspiration and expiration. these color ∗corresponding author: alieh zamani kiasari, intensive care unit, imam khomeini hospital, amirmazandarani bolivar, sari, iran. tel: 09111517833 email: aliehzamani@yahoo.com. changes are in response to co2 concentration changes. in the presence of a small amount of co2, the device has a base color, which changes gradually with increase in co2 concentration (5). a normal capnograph (figure 1) has a square-wave pattern, which begins in inspiratory phase (peak expiratory co2 (peco2) = 0 mmhg) and will continue until the expiratory phase (6). phase 0 (inspiratory phase): happens suddenly with an inspiration. the expiration phase includes three-phases: phase i (latency phase): beginning of expiration, represents anatomical dead space of the respiratory tract and is not discernible from the inspiratory phase before it (peco2 = 0 mmhg), phase ii: a very rapid increase in peco2, which represents exhalation of mixed air. phase iii (plateau phase): reflects the alveolar expiratory flow (a small increase in peco2), which happens the peak at the end of tidal expiration (etco2). in this phase peco2 is close to alveolar carbon dioxide tension (paco2). emergency physicians are always looking for a non-invasive, reliable instrument to detect life-threatening conditions in patients. one of the methods that have been suggested recently in the emergency department is capnography or etco2 monitoring. this study aimed to review the applications of etco2 monitoring in emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. aminiahidashti et al. 2 2. evidence acquisition a review of the literature was performed in november 2017 to find all previously published articles that included etco2 application in the emergency department. the review was done in multiple electronic databases (pubmed, google scholar, scopus, index copernicus, ebsco and cochrane database) using key words including etco2, emergency department monitoring, and critical monitoring, searching for articles published between 1966 and 2017. in addition, all references cited in these studies were searched for the keywords. all clinical trials, case reports, case series and meta-analyses were reviewed regarding their content. in the initial search, 386 articles were found and 65 articles were eligible to be included in this review. 3. etco2 applications 3.1. cardio pulmonary resuscitation (cpr) etco2 concentration is a reliable index of effective heart compression during cpr, which is associated with cardiac output (7, 8). the first sign of the return of spontaneous circulation (rosc) during cpr is increase in etco2, therefore monitoring of etco2 provides very useful information to guide treatment during cpr (8-10). etco2 is a reliable indicator with a high prognostic value in determining the cpr outcome (11, 12) . studies have shown that in patients who had etco2 of 10 mmhg or less, cardiac arrest was associated with death (13, 14). after 20 minutes of cpr, death occurs if etco2 is consistently below 10 mmhg, with 100% sensitivity and specificity (15). etco2 is more sensitive than cerebral oxygen saturations (rso2) in rosc prediction (16). 3.2. airway assessment confirmation of endotracheal intubation is vital in airway management in the emergency department, while there is no definitive diagnostic tool to verify correct intubation in emergency rooms (17). recently, capnography was used as the gold standard for confirming the correct location of the endotracheal tube (18, 19). colorimetric etco2 is a safe, reliable, simple and portable tool to determine the proper placement of endotracheal tube in patients with stable hemodynamic and it is very useful when a capnograph is not available (20) . however, when patients have a bag or mask ventilation or consume carbonated beverages or antacids it can cause a false positive result, yet it usually indicates the true result after 6 breaths (21). the use of sodium bicarbonate leads to a higher level of etco2 for 5 to 10 minutes (22). during a cardiac arrest, which leads to decrease in tissuepulmonary co2 transportation, capnography can show a correct intubation as a wrong one (false negative)(23). figure 1: diagram of a normal capnogram that includes the inspiratory and expiratory phase. 3.3. procedural sedation and analgesia capnography is an effective method to diagnose early respiratory depression and airway disorders, especially during sedation, leading to a reduction in serious complications (23, 24). capnography provided more safety in monitoring patients during sedation. oxygen prescription does not have an effect on respiratory function parameters evaluated by capnography (25). it shows impaired airway function sooner than any other device, 5 to 240 seconds earlier than pulse oximetry (26, 27). capnography is more sensitive than clinical evaluation in diagnosis of respiratory dysfunction, for instance, in many cases where apnea was experienced during sedation, doctors at the bedside did not recognize the apnea but capnography could identify it (28). 3.4. pulmonary disease 3.4.1. obstructive pulmonary disease in obstructive airway diseases, hypoventilation can cause shortness of breath and hypercarbia (29). there is a relationship between etco2 and partial arterial carbon dioxide (paco2) in patients with acute asthma in the emergency department (30, 31). capnography is dynamic monitoring of patients with acute respiratory distress conditions such as asthma, chronic obstructive pulmonary disease (copd), bronchiolitis, and heart failure (32). bronchospasm is associated with a prolonged expiratory phase (e1, e2, e3) in capnogram (figure 1) in patients with obstructive diseases such as copd (32, 33). changes in etco2 and expiratory phase slope correlated with (e1, e2, e3) forced expiratory volume in 1 second (fev1) and peak expiratory flow rate (pefr) (32, 34). etco2 is an indispensable tool in assessing the severity of obstructive respiratory disease in the emergency department. etco2 is higher in patients with copd exacerbation who are admitted to the hospital compared to those who are discharged from the emergency department (35). 3.4.2. pulmonary embolism in thromboembolism, etco2 is significantly lower than northis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e5 mal due to the reduction of pulmonary perfusion and increased alveolar dead space that reduces the amount of co2 exhaled from the lungs, so venous carbon dioxide pressure (pvco2) increases and all of these changes lead to an increase in arterial co2-etco2 gradient (36). this helps in correctly diagnosing pulmonary embolism, especially silent pulmonary embolism (37). volumetric capnography is used for monitoring of thrombolysis in large pulmonary embolism (38). the average value of etco2 and decrease in pco2 / po2 pressure for 30 seconds correlates with clinical probability or rule out of pulmonary embolism (39). 3.5. heart failure rapid differentiation of heart failure as the cause of dyspnea from other respiratory causes, is very important for choosing an appropriate therapy (40). sometimes distinguishing copd / asthma exacerbation and acute heart failure is very difficult, especially when both exist together, and treatment decisions in this situation are very complex (41). etco2 in patients with cardiac causes is markedly different from patients with respiratory distress due to obstructive causes. etc02 level > 37 mmhg was not observed in any patient with heart failure, although etc02 level > 37 mmhg has a slight sensitivity for diagnosis of copd / asthma (42, 43). etco2 level during cardiopulmonary exercise testing in patients with heart failure has high prognostic value for cardiac events (44, 45). n-terminal probrain natriuretic peptide on the side of quantitative capnography is very useful in early diagnosis and treatment of patients with acute dyspnea (respiratory or cardiac causes) in emergency departments. the widespread use of quantitative capnography can be beneficial in everyday work for emergency physicians (46). 3.6. shock hypotensive shock is a clinical feature for many diseases and is related to high mortality rate in emergency departments. emergency physicians continuously strive to find new ways to diagnose early-stage shock to start treatment as soon as possible (47). capnography is considered as a simple and non-invasive method to detect and estimate shock intensity in the early stage (48, 49). etco2 is known to be decreased in volume-related hypotensive states (50). etco2 has a correlation with blood pressure, serum lactate and base excess. in early-stage shock that is linked to reduced cardiac output, the amount of etco2 significantly decreases. this is due to decreased blood flow in the pulmonary artery during the cardiac output reduction, which disrupts ventilation perfusion ratio. with increase in shunt etco2 level decreases, while paco2 does not change (51, 52). with decrease in blood pressure, etco2 drops and paco2-etco2 gradient increases (53, 54). there is a correlation between the amount of dehydration and the amount of sodium bicarbonate and etco2, and etco2 can be used as a simple and non-invasive indicator for determination of dehydration (55). 3.7. metabolic disorder carbon dioxide (co2) is one of the final products of metabolism and is transferred to lungs through the blood circulation and transmitted through respiratory system, so exhaling co2 reflects the body’s metabolic status (56, 57). etco2 is a fast, inexpensive and non-invasive indicator to estimate the amount of hco3bicarbonate and paco2 in emergency and critical situations (58). due to the direct connection between etco2 and hco3, etco2 is a predictor of metabolic acidosis and mortality, so capnograph as a screening tool for metabolic acidosis is very useful in the emergency department (59) . etco2 can be recommended as a noninvasive method for determination of metabolic acidosis and can be used to detect early metabolic acidosis in patients with spontaneous breathing, however, abg should be used as the gold standard for diagnosis and management of treatment (60). 3.7.1. diabetic keto acidosis (dka) patients with diabetes mellitus are at increased risk of major and disabling complications, one of the most important of which is dka (61). the direct linear relationship between etco2 and hco3 is useful in prediction of acidosis. it was shown that there is no dka diagnosis when etco2 > 36, and there is dka diagnosis when etco2 ≥ 29. etco2 30 to 35 is considered as the cut –point, so it is clinically useful in diagnosis of acidosis (62, 63). in addition, a low paco2 level is correlated with increased risk of cerebral edema in children with dka (64). thus, according to the relationship between etco2 and paco2, capnography can be used to identify individuals with high risk of cerebral edema (62). when the patient’s glucose is above 550 mg/dl, etco2 is a useful tool to rule out the dka (65). 3.7.2. gastroenteritis among children with diarrhea and vomiting, etco2 is independently correlated with serum hco3 concentration. this is a non-invasive index for measuring the severity of acidosis in patients with gastroenteritis (66). etco2 can be used to estimate hco3 in many emergency situations(58). 3.8. trauma end-tidal carbon dioxide cannot be used to rule out severe injury in patients meeting the criteria for trauma care. etco2 ≥30 mmhg may be associated with increased risk of traumatic severe injury (67). there is a reverse relationship between pre-hospital etco2 and traumatic mortality rates, so etco2 can be used to improve triage and also helps the emergency medical service staff in planning for the transfer of patients to the appropriate trauma center (68). low etco2 has a strong association with shock in patients with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com h. aminiahidashti et al. 4 trauma and suggests the severity of the patient’s condition in the first 6 hours of admission (69). 4. conclusion: etco2 is used in the emergency department as an indicator for measurement in many clinical situations. capnography is a non-invasive and accurate method to measure etco2 and can help emergency physicians in some critical situations. although this is not used in many emergency situations and it is not used routinely in the emergency department, its application is increasing in many emergency situations, such as patients undergoing mechanical ventilation, procedural sedation and analgesia, pulmonary disease, heat failure, shock, metabolic disorder and trauma. this means that capnography must be considered as an essential tool in emergency department, however, more researches are needed to evaluate its application in specific clinical conditions and diseases. 5. appendix 5.1. acknowledgements none. 5.2. author’s contributions conception and design, collection of data and writing of the manuscript: hamed aminiahidashti; conception and design, and data interpretation: mohammad sazgar and sajad shafiee; conception and design, and critical revision of the manuscript: alieh zamani kiasari. 5.3. funding support none. 5.4. conflict of interest we declare no conflict of interest with any financial organization regarding the material discussed in the manuscript. references 1. o’flaherty. capnography: principles and practice. london: bmj publishing group. 1994. 2. smalhout b kz. an atlas of capnography. amsterdam: kerchebosch-zeist,. 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2016;34(11):2146-9. 68. childress k, arnold k, hunter c, ralls g, papa l, silvestri s. prehospital end-tidal carbon dioxide predicts mortality in trauma patients. prehospital emergency care. 2017:1-5. 69. stone me, kalata s, liveris a, adorno z, yellin s, chao e, et al. end-tidal co 2 on admission is associated with hemorrhagic shock and predicts the need for massive transfusion as defined by the critical administration threshold: a pilot study. injury. 2017;48(1):51-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction evidence acquisition applications in emergency department conclusion: appendix references archives of academic emergency medicine. 2019; 7 (1): e18 ca s e re p o rt pulmonary edema following intrathecal fluorescein injection; a case report faranak behnaz1∗, masih ebrahimy dehkordy1, hamidreza azizi faresani1, mohammadreza shahmohammadi2 1. anesthesiology department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. functional neurosurgery research center, shohadaye tajrish neurosurgical comprehensive center of excellence, shahid beheshti university of medical sciences, tehran, iran. received: november 2018; accepted: december 2018; published online: 12 february 2019 abstract: intrathecal fluorescein has been used widely for detection of cerebrospinal fluid (csf) leakage. after administration of fluorescein many serious complications may happen. pulmonary edema is one of the most serious complications that require emergency responses. in this study, we report a complicated case of pulmonary edema following intrathecal fluorescein injection. keywords: pulmonary edema; injections, spinal; fluorescein; emergency treatment; complications; cerebrospinal fluid leak cite this article as: behnaz f, ebrahimy dehkordy m, azizi faresani h, shahmohammadi m. pulmonary edema following intrathecal fluorescein injection; a case report. arch acad emerg med. 2019; 7 (1): e18. 1. introduction intrathecal injection of a sodium fluorescein solution following a thorough endoscopic examination has been used to identify the site of cerebrospinal fluid (csf) leakage (1, 2). sodium fluorescein has a relatively low molecular weight and is a highly water-soluble compound. it is well tolerated by most patients, but its intrathecal injection is an invasive procedure with an associated risk of complications. complication occurs in 5-10% of patients and ranges from mild to severe (3, 4). severe reactions are not common, but laryngeal edema, pulmonary edema, anaphylaxis, status epilepticus, myocardial infarction and cardiac arrest have been reported as some of its complications (5-7). non-allergic histamine release in the absence of antigen-antibody reaction (anaphylactoid reactions); vasovagal phenomenon resulting in bradycardia, arterial hypotension and reduced cardiovascular perfusion; immediate hypersensitivity reaction to the drug (anaphylactic reactions); anxiety-related medullary sympathetic discharge, eliciting tachycardia and myocardial stress; and direct vasospastic toxic effect of intravenous injection are among the proposed mechanisms for occurrence of complications (8-10). in this study, we report a compli∗corresponding author: faranak behnaz; anesthesiology department, shohadaye tajrish hospital, shardari av, tajrish sq, tehran, iran. zip code; 1989934148, email: faranak.behnaz@gmail.com tel: 00982122741174 cated case of pulmonary edema following intrathecal fluorescein injection. 2. case presentation: a 33-year-old man presented with 8-month history of intermittent cerebrospinal fluid (csf) leakage from his nostril following removal of fringe body from his orbital cavity. in medical history, the patient had eye trauma, mild asthma, and was under treatment of glaucoma with timolol eye drop. he was admitted to the operating room for transsphenoid endoscopic surgery. his preoperative blood pressure measured via noninvasive method was 135/80 mmhg and he had a pulse rate of 90/minute with normal respiratory rate and o2 saturation of 100% with oxygen. laboratory findings showed fasting blood sugar (fbs): 93 mg/dl, blood urea nitrogen (bun): 20 mg/dl, creatinine: 0.8 mg/dl, sodium: 138 meq/l, hemoglobin: 13.3 g/dl, platelet: 260000 /microliter, and international normalized ratio (inr): 1. his imaging result was normal, and normal cardiovascular risk for operation was reported in pre-operation cardiology consultation. he underwent cardiac and invasive blood pressure (ibp) monitoring, pulse oximetry, capnometry, and intake/output checking. anesthesia was induced via fentanyl (200 micg), midazolam (2 mg), lidocaine (80 mg), propofol (200 mg), cisatracuriom (18 mg), and then orotracheal intubation was done. after positioning of the patient, 0.5 cc of fluorescein 5% was mixed with 10 cc of the patient’s csf this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. behnaz et al. 2 figure 1: changes observed 10 minutes after intrathecal fluorescein injection. and then re-injected via a lumbar puncture at the level of l4-l5 spinal column. after 10 minutes, the patient’s blood pressure dropped unexpectedly (ibp: 87/50 mmhg), and his pulse rate rose to 124/minutes and o2 saturation dropped to 85%. shortly after this event, some pink foamy secretions appeared in the transparent circuiting tube of the anesthesia machine and suction bottle cavity and urine color changed to shiny green (figure 1). patient underwent immediate supportive vital managements including change of ventilator set up, medical administration of supportive drugs, and close vital signs and hemodynamic monitoring. the surgeon decided to postpone the surgery. the patient was directly transferred to intensive care unit (icu) and ventilated with positive pressure mode. after one day, the intensivist decided to wean him from mechanical ventilation and he was extubated successfully. finally, the patient was discharged from the hospital with good general condition after two days from his admission. 3. discussion the use of intrathecal fluorescein injection (in the subarachnoid space) for detecting the source of leakage, dates back to 1960, when kirchner and proud used this method to recognize and locate csf fistulas in the cranial base (11). fluorescein quickly diffuses out of the capillaries into the extravascular fluid compartments. in the circulation, fluorescein moves mostly bound to plasma proteins and is metabolized in the liver through glucuronidation. the monoglucuronide has about 4.5% of the fluorescence of free fluorescein, and both are excreted through the kidney. while most fluorescein is eliminated after 24 hours, it can still be traced in urine up to a week after its infusion (12). the usefulness of this test depends on the extent of the dural defect, rate of leakage, timing of the intrathecal injection, and rate of csf turnover that could dilute or disperse the fluorescein. reported complications of the solution’s injection, and thus limitations to its use, have ranged from mild to severe among which are tinnitus, headache, nausea and vomiting, transient pulmonary edema, confusion, seizures, and coma, and death. guimaraes r et al. reported that when they used a low dose of fluorescein (0.25cc of 5% solution) and diluted it with csf and injected the solution slowly, complications did not happen (13). the reasons for the complications were found in the method of administration, formulation of the solution, idiopathic reactions, and concentration or dose of fluorescein (13-15). side effects after the administration of intravenous fluorescein are uncommon and mostly harmless. reactions more commonly seen include nausea and occasional vomiting. severe reaction following intravenous fluorescein injection was observed in a patient who had an anaphylactic reaction (8). the exact mechanism of fluorescein-induced pulmonary edema following intrathecal injection is not known and it could happen due to multiple factors. hypertension with overloading of the left ventricle and chemical alveolitis may cause pulmonary edema with fluorescein. a central neurogenic mechanism may play a role in the pulmonary changes (16). although our patient had no underlying heart disease, bronchopulmonary infection, or any other risk factor of pulmonary edema, intrathecal fluorescein injection could be considered as a causative factor for pulmonary edema. anesthesiologists and medical practitioners should be aware of this serious adverse reaction of administrating this drug. 4. conclusion: medical practitioners should be aware of the complications of intrathecal fluorescein administration. 5. appendix 5.1. acknowledgements we are very thankful to anesthesiology research center, shahid beheshti university of medical sciences, tehran, iran. 5.2. authors contribution faranak behnaz (first author), research designer, masih ebrahimy dehkordy (second author) writing the manuscript, hamidreza aziz faresani (third author) research consultant and mohammadreza shahmohammadi (fourth author) research consultant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e18 authors orcids faranak behnaz: 0000-0003-2856-3975 masih ebrahimy dehkordy: 0000-0001-5779-6204 hamidreza azizi faresani: 0000-0002-4561-6066 mohammadreza shahmohammadi: 0000-0003-4803-8027 5.3. conflict of interest none. 5.4. funding and support none. references 1. hawkins bt, egleton rd. fluorescence imaging of blood– brain barrier disruption. journal of neuroscience methods. 2006;151(2):262-7. 2. javadi sah, samimi h, naderi f, shirani m. the use of low-dose intrathecal fluorescein in endoscopic repair of cerebrospinal fluid rhinorrhea. archives of iranian medicine. 2013;16(5):264. 3. lira rpc, oliveira clda, marques mvrb, silva ar, pessoa cdc. adverse reactions of fluorescein angiography: a prospective study. arquivos brasileiros de oftalmologia. 2007;70(4):615-8. 4. moosbrugger ka, sheidow tg. evaluation of the side effects and image quality during fluorescein angiography comparing 2 ml and 5 ml sodium fluorescein. canadian journal of ophthalmology/journal canadien d’ophtalmologie. 2008;43(5):571-5. 5. jacob ak, dilger ja, hebl jr. status epilepticus and intrathecal fluorescein: anesthesia providers beware. anesthesia & analgesia. 2008;107(1):229-31. 6. bennett tj, quillen da. fundamentals of fluorescein angiography. curr concepts ophthalmology. 2001;9(3):439. 7. dilek o, ihsan a, tulay h. anaphylactic reaction after fluorescein sodium administration during intracranial surgery. journal of clinical neuroscience. 2011;18(3):4301. 8. bearelly s, rao s, fekrat s. anaphylaxis following intravenous fluorescein angiography in a vitreoretinal clinic: report of 4 cases. canadian journal of ophthalmology. 2009;44(4):444-5. 9. xu k, tzankova v, li c, sharma s. intravenous fluorescein angiography–associated adverse reactions. canadian journal of ophthalmology/journal canadien d’ophtalmologie. 2016;51(5):321-5. 10. hyder mf, khan tp, munawar cmt. incidence of complications during fluorescein fundus angiography (ffa) in our population. seizure. 2012;5:7. 11. kirchner f, proud g. method for the identification and localization of cerebrospinal fluid, rhinorrhea and otorrhea. the laryngoscope. 1960;70(7):921-31. 12. antunes p, perdigao m. the use of intrathecal fluorescein in cerebrospinal fluid leak repair: management from an anesthesiologist’s point-of-view. acta anaesthesiologica scandinavica. 2016;60(9):1323-7. 13. guimaraes r, becker h. a new technique for the use of intrathecal fluorescein in the repair of cerebrospinal fluid rhinorrhea using a hypodense diluent. revue de laryngologie-otologie-rhinologie. 2001;122(3):191-3. 14. keerl r, weber rk, draf w, wienke a, schaefer sd. use of sodium fluorescein solution for detection of cerebrospinal fluid fistulas: an analysis of 420 administrations and reported complications in europe and the united states. the laryngoscope. 2004;114(2):266-72. 15. ozturk k, karabagli h, bulut s, egilmez m, duran m. is the use of topical fluorescein helpful for management of csf leakage? the laryngoscope. 2012;122(6):1215-8. 16. hess j, pacurariu r. acute pulmonary edema following intravenous fluorescein angiography. american journal of ophthalmology. 1976;82(4):567-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation: discussion conclusion: appendix references archives of academic emergency medicine. 2020; 8(1): e59 or i g i n a l re s e a rc h seizure prediction model in acute tramadol poisoning; a derivation and validation study elham bazmi1, behnam behnoush2, saeed hashemi nazari1, soheila khodakarim1, amir hossein behnoush3, hamid soori4∗ 1. department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 2. department of forensic medicine, tehran university of medical sciences, tehran, iran. 3. tehran university of medical sciences, tehran, iran. 4. safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. received: may 2020; accepted: may 2020; published online: 17 may 2020 abstract: introduction: seizure is a common complication of tramadol poisoning and predicting it will help clinicians in preventing seizure and better management of patients. this study aimed to develop and validate a prediction model to assess the risk of seizure in acute tramadol poisoning. methods: this retrospective observational study was conducted on 909 patients with acute tramadol poisoning in baharloo hospital, tehran, iran, (2015-2019). several available demographic, clinical, and para-clinical characteristics were considered as potential predictors of seizure and extracted from clinical records. the data were split into derivation and validation sets (70/30 split) via random sampling. derivation set was used to develop a multivariable logistic regression model. the model was tested on the validation set and its performance was assessed with receiver operating characteristic (roc) curve. results: the mean (standard deviation (sd)) of patients’ age was 23.75 (7.47) years and 683 (75.1%) of them were male. seizures occurred in 541 (60%) patients. univariate analysis indicated that sex, pulse rate (pr), arterial blood carbone dioxide pressure (pco2), glasgow coma scale (gcs), blood bicarbonate level, ph, and serum sodium level could predict the chance of seizure in acute tramadol poisoning. the final model in derivation set consisted of sex, pr, gcs, ph, and blood bicarbonate level. the model showed good accuracy on the validation set with an area under the roc curve of 0.77 (95% ci: 0.67–0.87). conclusion: representation of this model as a decision tree could help clinicians to identify high-risk patients with tramadol poisoninginduced seizure and in decision-making at triage of emergency departments in hospitals. keywords: clinical decision-making; tramadol; poisoning; seizures cite this article as: bazmi e, behnoush b, hashemi nazari s, khodakarim s, behnoush a h, soori h. seizure prediction model in acute tramadol poisoning; a derivation and validation study. arch acad emerg med. 2020; 8(1): e59. 1. introduction tramadol is a synthetic opioid analgesic used for alleviation of moderate to severe pain. this drug weakly binds to µ opioid receptors and inhibits the reuptake of monoamines such as serotonin and norepinephrine in the central nervous system (1, 2). in recent years, easy and wide availability, excessive prescription, and euphoria effects of this drug have caused a rapid increase in tramadol consumption and poisoning in iran (3∗corresponding author: hamid soori; safety promotion and injury prevention research center, shahid beheshti university of medical sciences, tehran, iran. email: hsoori@yahoo.com; tel: +98212243980 5). seizure is a common, serious neurological side effect of tramadol consumption in various doses, which is associated with several complications such as lactic acidosis and rhabdomyolysis (6). although, previous investigations indicated that tramadol-induced seizure occurrs due to inhibition of gamma amino butyric acid (gaba) receptors and serotonin toxicity, the exact mechanism of tramadol induced seizure is still unknown (7-9). several studies have shown associations between seizure and related factors such as opioid dependency, age, sex, consumption dose, blood concentration, and delayed hospital admission, but their effects are still under debate and other related factors have remained unclear (5, 10-12). having a prediction model that discriminates patients who will dethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bazmi et al. 2 velop seizure, can help clinicians in quickly detecting highrisk patients and immediately taking suitable action. several investigations have been done to develop prediction models of several types of seizure by using effective factors and various analytic methods such as frequency–based methods, statistical analysis of eeg signals, least absolute shrinkage and selection operator (lasso) regression, non-linear dynamics (chaos), logistic regression and machine learning models like support vector machine (svm) (13-16). in spite of various reports of research, to date, no prediction model is available for tramadol induced seizure. a prediction model should consist of variables that are readily available in clinic and needs to be parsimonious (17). also, in previously suggested prediction models, there is not a suitable trade-off between simplicity and accuracy of model, and they are not widely applicable in the emergency department due to the complexity of their utilization as a clinical tool. this study aimed to develop and validate a prediction model to assess the risk of seizure in acute tramadol poisoning by using demographic, clinical and para-clinical factors of patients admitted to the emergency department of a hospital in a regression model and developing a decision tree based on the final model as a clinical decision instrument. 2. methods 2.1. study design and setting this retrospective, single center, cohort study of routinely collected clinical data was performed on acute tramadol intoxicated patients who had referred to the emergency department (ed) of baharloo hospital (a poisoning referral center), tehran, iran, in the 5-year period between september 2015 and november 2019. several available demographic, clinical, and laboratory characteristics were considered as potential predictors of seizure and extracted from clinical records. the data were split into derivation and validation sets (70/30 split) using random sampling. derivation set was used to develop a multivariable logistic regression model. the model was tested on the validation set and its performance was assessed via receiver operating characteristic (roc) curve. this study was approved by ethical committee of shahid beheshti university of medical sciences (ir.sbmu.phns.rec.1398.110). all individual information was kept confidential and data analysis was done anonymously. in this research, we followed the reporting guideline from the tripod (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement (18). 2.2. participants all patients with a history of tramadol overdose, confirmed by laboratory test results, were included in this research (909 patients). we excluded patients aged less than 15 years, as well as those with history of renal, hepatic, cardiovascular and respiratory disorders, epilepsy, co-ingestion of other drugs, recent seizure history, pregnancy and missing data in clinical records. 2.3. data gathering the data were extracted from clinical records and hospital’s electronic system, which were registered based on the examination of patients at the time of admission to ed performed by two trained researchers. extracted data included demographic, clinical, and laboratory ones. as the predictors for development of model, we included routinely available information at ed settings. demographic variables consisted of age, sex, ingested dose, history of opioid addiction, time elapsed from consumption, and manner of poisoning; clinical variables consisted of systolic blood pressure, diastolic blood pressure, glasgow coma scale (gcs), pulse rate (pr), respiratory rate (rr), and laboratory variables included arterial blood oxygen pressure (po2), arterial blood carbone dioxide pressure (pco2), blood oxygen saturation levels (o2sat), blood bicarbonate level, platelet count, hemoglobin level (hb), white blood cell count (wbc), blood sugar, and serum sodium and potassium levels. 2.4. reference standard in this study, the gold standard was occurrence of seizure, defined as an episode of neurologic dysfunction caused by abnormal neuronal activity that results in a sudden change in behavior, sensory perception, or motor activity (19). tramadol-induced seizures, as outcome of this research, are frequently reported to be generalized, tonic-clonic in nature, and without auras or focal symptoms, and occur during the first 24 hours after admission to ed and are diagnosed via clinical observations and confirmed using electroencephalogram (eeg) in suspected patients. 2.5. statistical analysis information of 909 patients with acute tramadol poisoning who were admitted to ed was evaluated in this study. the analyses were performed using stata software version 16.1 and r software version 3.6.2. data were split into derivation (70%) and validation sets (30%) using random sampling. data in the derivation set were applied to develop prediction models and data of validation set were used to evaluate the model’s performance and compare predicted probability with actual patient outcomes. in descriptive statistics, the baseline characteristics and prevalence of seizure were analyzed in both derivation and validation datasets to assure similarity. in derivation set, predictor variables were identified via univariate logistic regression analysis, performed on all variables to assess their this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e59 figure 1: flow of all patients referred to the emergency department from september 2015 to november 2019 in seizure prediction study. figure 2: receiver operating characteristic (roc) curve of the seizure prediction model in validation set. ability to predict seizure. the prediction model was developed by using stepwise logistic regression on the derivation set. we trained several models to choose potential contributfigure 3: calibration plot of the seizure prediction model in validation set. ing predictors, which were included in the final prognostic model (p value<0.05 was considered as statistically significant in stepwise selection). the performance of the final model, including its discrimination and calibration, was evaluated in both derivation and validation sets. the discrimination of the model was measured via k-fold cross validation (k=10) method using the area this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bazmi et al. 4 figure 4: the decision tree plot to assess the risk of seizure in acute tramadol poisoning. example: at the top of the plot, the overall probability of seizure is shown (0.58). therefore, the node asks whether the pulse rate (pr) of patients is lower than 96. if yes, then it goes down to the root’s left child node. 48% of patients had pr<96 with a seizure probability of 0.46. in the second node, if the ph is higher than 7.4, the chance of seizure occurrence is 0.27. yes and no in the nodes indicate the prediction of seizure occurrence. under the curve (auc) in the receiver operating characteristic (roc) analysis. the calibration of the model was assessed via hosmer-lemeshow statistic and plotting the calibration curve with "caret" package in r and creating 10 bins for predicted probabilities of seizure and choosing the bin midpoints for observed seizure rates. also, prediction performance was evaluated using confusion matrix results such as sensitivity, specificity, positive predictive values (ppv ), negative predictive values (npv ) of the final model in the validation set. we developed a decision tree plot to represent choices and model results to the risk of seizure in tramadol poisoning. the nodes in the graph represent an event (seizure=yes and seizure=no) and the edges of the graph indicate the decision rules. 3. results 3.1. baseline characteristic of patients in this study, 1176 patients with acute tramadol poisoning were identified. among them, 267 patients were excluded and 909 patients were enrolled in our investigation. figure 1 shows the flow of the total number of patients referred to the ed in our dataset. the mean (standard deviation (sd)) age of the patients was 23.75 (7.47) years, their age range was 16-65 years and 683 (75.1%) of them were male. the most common cause of poisoning was suicide, which occurred in 644 (71%) patients and 427 (47%) subjects had a history of addiction to opioids. seizure occurred in 541 (59.8%) of the patients with acute tramadol toxicity. the time interval between tramadol ingestion and hospital admission was 4.95 ± 4.1 hours and the mean (sd) of the last dose of tramadol consumption was 1770 ± 918.8 mg. demographic, clinical, and laboratory characteristics of patients in derivation and validation sets are shown in table1. the baseline characteristics and proportion of patients who experienced seizure on the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e59 table 1: demographic, clinical and laboratory characteristics of patients in derivation and validation sets of seizure prediction model in acute tramadol poisoning characteristics derivation set (n=641) validation set (n=268) age (year) mean ± sd 23.3 ± 7.2 24.6 ± 7.8 sex male 485(75.7) 198(74) female 156(24.3) 70(26) last dose of ingestion (mg) mean ± sd 1736 ± 170 1783 ± 209 ingestion to admission (hour) mean ± sd 5 ± 4.1 4.7± 3.3 addiction history yes 304 (47.4) 123(45.9) no 337 (52.6) 145(54.1) cause of poisoning suicide 453 (70.7) 191 (71.3) accidental 20 (3.1) 11 (4.1) overdose 142 (22.2) 54 (20.1) unknown 24 (3.7) 11 (4.1) vital signs systolic blood pressure (mmhg) 121.8 (16.2) 122.1 (15.4) diastolic blood pressure (mmhg) 75.1 (11.4) 74.5 (10.9) respiratory rate (breath/minute) 75.1 (11.2) 76.3 (13.4) pulse rate (pulse/minute) 98.2 (20.5) 98.9 (19.6) glasgow coma scale 14.1 (1.9) 14.1 (1.8) laboratory white blood cell (103/mm) 10.5(3.6) 10.7 (3.5) hemoglobin (g/dl) 14.6 (2.4) 14.5 (2.3) platelet (103/µl) 239.7 (72.3) 245.6 (81.9) ph 7.3 (.12) 7.2 (.09) po2 (mmhg) 81.5 (23.8) 82.9 (19.9) pco2 (mmhg) 43.9 (10) 44.2 (10.7) blood bicarbonate level (mmol/l) 22 (3.8) 21.9 (4) o2 saturation (%) 0.92 (.06) 0.93 (.07) blood sugar (mg/dl) 110.3 (77.1) 109.3 (38.6) sodium level (meq/l) 140.7 (4.1) 141.3 (3.7) potassium level (meq/l) 3.9 (.3) 3.8 (.2) data are presented as mean ± standard deviation (sd) or frequency (%). table 2: final variables included in the prediction model in multivariate logistic regression model in derivation set variables rc se wald test p value or (%95 ci) pulse rate .015 .004 3.38 .0007 1.015(1.01-1.02) glasgow coma scale -.158 .056 -2.8 .0051 .871(.78-.973) ph -2.334 .892 -2.61 .0091.006.106(.018-.618) blood bicarbonate level -.106 .024 -4.42 <0.0001 .905(.863-.949) sex .845 .201 4.19 <0.0001 2.348(1.58-3.5) intercept 26.63 7.54 3.53 0.0004 1222299928.3 rc: regression coefficient; or: odds ratio; se: standard error; ci: confidence interval. derivation and validation datasets were similar. 3.2. development of prediction model based on univariate analysis, being male (or=2.39; 95% ci:1.47-3.87), increase in pulse rate (or=1.33; 95% ci:1.11-1.45) and arterial blood carbon dioxide pressure (or=1.16;95%ci:.1.1-1.22) and decrease in gcs (or=0.88; 95%ci:0.78-0.99), blood bicarbonate level (or=0.9; 95%ci: 0.832-.937), ph (or=0.26; 95%ci: 0.20-0.31), and sodium level (or=0.95; 95%ci:0.9-0.99) significantly increased the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bazmi et al. 6 table 3: the screening performance characteristics of the model in derivation and validation sets characteristics derivation set validation set cut-point 0.60 (0.55-0.68) 0.60 (0.55-0.68) sensitivity 0.85 (0.81-0.88) 0.80 (0.78-0.88) specificity 0.40 (0.36-0.48) 0.60 (0.56-0.67) positive predictive values 0.73 (0.69-0.74) 0.71 (0.63-0.76) negative predictive values 0.67 (0.61-0.70) 0.64 (0.58-0.71) positive likelihood ratio 0.63 (0.60-0.67) 0.40 (0.36-0.43) negative likelihood ratio 0.41 (0.35-0.43) 0.35 (0.31-0.39) area under curve 0.79 (0.71-0.76) 0.77 (0.70-0.8) accuracy 0.73 (0.72-0.78) 0.75 (0.70-0.79) hosmerlemeshow k2 (p value) 9.4 (0.31) 2.7 (0.95) all data are presented with 95% confidence interval (ci). chance of seizure in acute tramadol poisoning. the final model obtained by multivariable logistic regression analysis with corresponding adjusted odds ratio and 95% ci in derivation set is shown in table 2. in this model, male sex, high pulse rate, low ph, low blood bicarbonate level, and low gcs would significantly increase the probability of tramadol-induced seizure. 3.3. screening performance of prediction model in evaluating the performance of the model in derivation and validation sets, area under the roc curve (auc) of the final model were 0.791 (95% ci: 0.713-0.910) and 0.774 (95% ci: 0.675-0.874), respectively, which indicated good discriminatory power. the curves are shown in figure 2. the optimal threshold cut-off value was 0.6, which was determined by the highest youden index value. in the final model, this maximized sensitivity (0.80; 95% ci: 0.745-0.890) and specificity (0.60; 95% ci: 0.588-0.68). positive predictive value (ppv ) was 0.71 (95% ci: 0.63-0.76) and negative predictive value (npv ) was 0.64 (95% ci: 0.580-0.71) in our data. the performance characteristics of the model in derivation and validation sets are presented in table 3. figure 3 shows good agreement between the predicted and observed cases of seizure in the calibration curve of our prediction model in validation set. 3.4. decision tree we suggested the model with 5 potential predictors including sex, pr, gcs, blood bicarbonate level and ph and presented it as a decision tree in figure 4. at the top of the plot, the overall probability of seizure was observed (0.58). therefore, the node asks whether the pr of patients is lower than 96. if yes, then it goes down to the root’s left child node. 48% of patients had pr<96 with a seizure probability of 0.46. in the second node, if the ph is higher than 7.4, the chance of seizure occurrence is 0.27. 4. discussion in this research, we developed a prognostic model to identify patients at high risk for seizure among those with acute tramadol poisoning by using routinely available demographic, clinical and laboratory predictors and validated the model by applying it on another dataset. in this study, the rate of seizure following tramadol poisoning (60%) was similar to previous reports in iran, which reported that seizure occurred in 15% to 65% of tramadol poisoned patients. different seizure rate ranges in other poisoning centers are due to differences in study methods, sample sizes and dose and pattern of tramadol consumption (20-24). the wide range of the last dose of ingested tramadol (100 to 3000 mg) in this investigation indicated seizures due to tramadol toxicity were dose-independent. therefore, reported dose of consumption could not predict seizure. this finding is consistent with the results of other investigations (22, 25, 26). previously, another research had reported that although higher doses of tramadol correlated with higher blood concentration, it was not associated with seizure (21, 25). on the other hand, some studies reported dose-dependent characteristics of seizure in tramadol overdose (8, 23). the reason for this inconsistency is drug dependency and individuals’ tolerance. also, various racemic formulations of tramadol in iran cause different pharmacokinetics and pharmacodynamic characteristics (27). difference between the minimum dose of tramadol consumed in our study and other investigations is due to purity and concentration of active ingredients’ formulation of tramadol tablets, ambiguity about quantity of ingested tables, and their dose in patients with seizures in these studies (22). in our research, the mean time interval between drug ingestion and seizure was 5 hours (range: 30 minutes to 24 hours) and it usually occurred in the first 24 hours after consumption, which is consistent with other investigations (6, 21, 22, 25). most of the patients with acute tramadol toxicity were male this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e59 with the mean age of 23.75±7.46 years, which is in line with other reports (26, 28, 29). our findings could be explained by increasing drug abuse among young men trying to distance themselves from social and financial problems by using opioid drugs such as tramadol. predictive variables provide the full multivariate model with high discriminative ability, which is the result of repeated clinical practices in emergency department of hospitals. previous studies indicated that a model with multiple variables, such as our full model, which is based on demographic, clinical and laboratory characteristics, has better performance in prediction of seizure compared to models with only one of them (such as eeg) (6, 29). in our study, patients with lower blood bicarbonate level (<17.1) and lower ph (<7.27) were at high risk for seizure within the initial 24 hours after admission to emergency departments. the results of other studies showed that ph, lactate and other blood gases could predict occurrence and recurrence of seizure, which is in line with our findings. also, other research reported that, serum laboratory testing and arterial blood gas analysis might be helpful for differentiating between generalized seizure and syncope in patients who experienced a transient loss of consciousness and were referred to the emergency department (30-34). pulse rate was an important factor for tramadol poisoning-induced seizure prediction in our research, which is similar to other studies. the results of these investigations proposed seizures prediction algorithms based on heart rate variation and ecg changes. although, the recording of ecg was much easier and faster than electroencephalogram (eeg), ecg and pr had less value than eeg (35, 36). our findings showed that sodium blood level significantly correlated with the occurrence of seizures, which was confirmed in other investigations. moreover, the clinical manifestations of hyponatremia were associated with cns dysfunctions, a rapid decrease in serum sodium level in routine laboratory findings could cause neuronal activity depression and cerebral edema with neurologic symptoms such as eeg changes and seizures (37, 38). the results of our logistic regression analysis showed that simple and easy blood tests could be a valuable help for clinicians in predicting tramadol poisoning-induced seizure by determining electrolyte levels and blood gas pressure. the analysis of receiver operation characteristics (roc) curve of sex, gcs, ph, blood bicarbonate level and pulse rate as predictors of seizure occurrence showed a cut-off value of 0.66, 0.63, 0.63, 0.67, and 0.67, respectively that were able to predict 0.77 of cases who would develop seizures. the main strength of our prediction model is the size of the data set used for its development. this is among the largest data sets used to develop a seizure prediction model in tramadol toxicity. also, due to simplicity and good calibration and discrimination of our model, we could have presented this model as a nomogram to calculate the probability of seizure occurrence at the time of patients’ presentation to ed. 5. limitation there were several limitations in this study. firstly, we excluded samples with missing information, which could have affected our data analysis. yet, missing data was negligible (less than 6%). secondly, our final prediction model was based on data from a single center. therefore, development of an algorithm using multicenter data to confirm this model seems necessary. 6. conclusion in this investigation, a validated model was developed to predict seizure in acute tramadol poisoning cases based on readily available demographic, clinical and laboratory information. presentation of this model as a simple and easy to use nomogram could help clinicians to identify high risk patients for tramadol induced seizure and facilitate decision-making at triage of emergency departments in hospitals. 7. declarations 7.1. acknowledgements we are grateful to the original team involved with the collection of data in baharloo hospital (a poisoning referral center) in tehran, iran. 7.2. author contribution all authors contributed equally to this work. also, all authors read and approved the final version of the manuscript and met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids elham bazmi: 0000-0003-0038-3171 behnam behnoush: 0000-0002-2510-5285 saeed hashemi nazari: 0000-0002-0883-3408 soheila khodakarim: 0000-0002-5473-999x amirhossein behnoush: 0000-0002-9955-4227 hamid soori: 0000-0002-3775-1831 7.3. funding/support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. conflict of interest the authors report no conflicts of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bazmi et al. 8 references 1. rostam-abadi y, gholami j, amin-esmaeili m, safarcherati a, mojtabai r, ghadirzadeh mr, et al. tramadol use and public health consequences in iran: a systematic review and meta-analysis. addiction. 2020. 2. minami k, ogata j, uezono y. what is the main mechanism of tramadol? naunyn schmiedebergs arch pharmacol. 2015;388(10):999-1007. 3. hafezi moghadam p, zarei n, farsi d, abbasi s, mofidi m, rezai m, et al. electrocardiographic changes in patients with tramadol-induced idiosyncratic seizures. turk j emerg med. 2016;16(4):151-4. 4. okazi a, taghaddosinejad n, mazrouei n, forouzesh m, barzegar a, f f. occurrence and recurrence of seizures and related factors in patients with tramadol ingestion. ijmtfm. 2018;8(3):101-8. 5. shokrzadeh m, hajimohammadi a, delaram a, y s. characteristics of patients hospitalized with tramadol intoxication in gorgan, iran, 20082015. j mazandaran univ med sci. 2017;26(146):185-90. 6. taghaddosinejad f, mehrpour o, afshari r, seghatoleslami a, abdollahi m, dart rc. factors related to seizure in tramadol poisoning and its blood concentration. j med toxicol. 2011;7(3):183-8. 7. rehni ak, singh i, kumar m. tramadol-induced seizurogenic effect: a possible role of opioid-dependent gamma-aminobutyric acid inhibitory pathway. basic clin pharmacol toxicol. 2008;103(3):262-6. 8. sun c, mtchedlishvili z, erisir a, kapur j. diminished neurosteroid sensitivity of synaptic inhibition and altered location of the alpha4 subunit of gaba(a) receptors in an animal model of epilepsy. j neurosci. 2007;27(46):12641-50. 9. baldo ba. opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects. arch toxicol. 2018;92(8):2457-73. 10. koushesh hr, afshari r, afshari r. a new illicit opioid dependence outbreak, evidence for a combination of opioids and steroids. drug chem toxicol. 2009;32(2):114-9. 11. afshari r, majdzadeh r, balali-mood m. pattern of acute poisonings in mashhad, iran 1993-2000. j toxicol clin toxicol. 2004;42(7):965-75. 12. ahmadimanesh m, shadnia s, rouini mr, sheikholeslami b, ahsani nasab s, ghazi-khansari m. correlation between plasma concentrations of tramadol and its metabolites and the incidence of seizure in tramadol-intoxicated patients. drug metab pers ther. 2018;33(2):75-83. 13. zhang jh, han x, zhao hw, zhao d, wang n, zhao t, et al. personalized prediction model for seizure-free epilepsy with levetiracetam therapy: a retrospective data analysis using support vector machine. br j clin pharmacol. 2018;84(11):2615-24. 14. yadollahpour a, m j. seizure prediction methods: a review of the current predicting techniques. biomed pharmacol j 2014;7(1). 15. hussain l. detecting epileptic seizure with different feature extracting strategies using robust machine learning classification techniques by applying advance parameter optimization approach. cogn neurodyn. 2018;12(3):27194. 16. allotey j, fernandez-felix bm, zamora j, moss n, bagary m, kelso a, et al. predicting seizures in pregnant women with epilepsy: development and external validation of a prognostic model. plos med. 2019;16(5):e1002802. 17. parker ca, liu n, wu sx, shen y, lam ssw, ong meh. predicting hospital admission at the emergency department triage: a novel prediction model. am j emerg med. 2019;37(8):1498-504. 18. moons kg, altman dg, reitsma jb, ioannidis jp, macaskill p, steyerberg ew, et al. transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (tripod): explanation and elaboration. ann intern med. 2015;162(1):w1-73. 19. chari g, yadav k, nishijima d, omurtag a, zehtabchi s. improving the ability of ed physicians to identify subclinical/electrographic seizures on eeg after a brief training module. int j emerg med. 2019;12(1):11. 20. abbasi b, hafezimoghadam p, ansari nejad n, sarvari m, t r. assessment of time interval between tramadol intake and seizure and second drug-induced attack. tehran univ med j. 2015;73(8):592-9. 21. talaie h, panahandeh r, fayaznouri m, asadi z, abdollahi m. dose-independent occurrence of seizure with tramadol. j med toxicol. 2009;5(2):63-7. 22. habibollahi p, garjani a, shams vahdati s, sadatebrahimi sr, parnianfard n. severe complications of tramadol overdose in iran. epidemiol health. 2019;41:e2019026. 23. babahajian a, khomand p, manouchehri f, fakhimi r, ahsan b, amjadian m, et al. seizure prevalence and its related factors in tramadol intoxication; a brief report. arch acad emerg med. 2019;7(1):e28. 24. emamhadi m, sanaei-zadeh h, nikniya m, zamani n, dart rc. electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. am j emerg med. 2012;30(8):14815. 25. jovanovic-cupic v, martinovic z, nesic n. seizures associated with intoxication and abuse of tramadol. clin toxicol (phila). 2006;44(2):143-6. 26. shadnia s, brent j, mousavi-fatemi k, hafezi p, soltaninejad k. recurrent seizures in tramadol intoxication: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e59 implications for therapy based on 100 patients. basic clin pharmacol toxicol. 2012;111(2):133-6. 27. vazzana m, andreani t, fangueiro j, faggio c, silva c, santini a, et al. tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, coadministration of drugs and new drug delivery systems. biomed pharmacother. 2015;70:234-8. 28. rahimi hr, soltaninejad k, shadnia s. acute tramadol poisoning and its clinical and laboratory findings. j res med sci. 2014;19(9):855-9. 29. arwa a. abuelfadl , ahmad a. el-ebiary, soleiman ma. tramadol blood level and prediction of seizures in patients with acute tramadol poisoning. mansoura j forensic med clin toxicol 2016;24(2):35-47. 30. dadpour b, alizadeh a, vahabzadeh m, mousavi sr, moshiri m, ataee z, et al. arterial blood gas analysis of patients with tramadol-induced seizure; a cross sectional study. arch acad emerg med. 2020;8(1):e14. 31. morrow rl, dormuth cr, paterson m, mamdani mm, gomes t, juurlink dn. tramadol and the risk of seizure: nested case-control study of us patients with employersponsored health benefits. bmj open. 2019;9(3):e026705. 32. käśläśc ty, yesilaras m, atilla od, sever m, aksay e. can venous blood gas analysis be used for predicting seizure recurrence in emergency department? world j emerg med. 2014;5(3):187-91. 33. nass rd, sassen r, elger ce, surges r. the role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures. seizure. 2017;47:51-65. 34. choi sk, lim ys, g gl. . seizure or syncope: the usefulness of serum laboratory tests and arterial blood gas analysis for making the differential diagnosis.j korean soc emerg med. 2010;21(5):606-14. 35. moridani mk, farhadi h. heart rate variability as a biomarker for epilepsy seizure prediction. bratisl lek listy. 2017;118(1):3-8. 36. billeci l, marino d, insana l, vatti g, varanini m. patientspecific seizure prediction based on heart rate variability and recurrence quantification analysis. plos one. 2018;13(9):e0204339. 37. nardone r, brigo f, trinka e. acute symptomatic seizures caused by electrolyte disturbances. j clin neurol. 2016;12(1):21-33. 38. bhardwaj a. neurological impact of vasopressin dysregulation and hyponatremia. ann neurol. 2006;59(2):229-36. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e31 le t t e r to ed i to r incidentally diagnosed covid-19 infection in trauma patients; a clinical experience mehdi khazaei1, reyhaneh asgari1, ehsan zarei1, yashar moharramzad1, hamidreza haghighatkhah1, morteza sanei taheri1∗ 1. department of radiology, shahid beheshti university of medical sciences, tehran, iran. received: march 2020; accepted: march 2020; published online: 23 march 2020 cite this article as: khazaei m, asgari r, zarei e, moharramzad y, haghighatkhah h, sanei taheri m.incidentally diagnosed covid-19 infection in trauma patients; a clinical experience. arch acad emerg med. 2020; 8(1): e31. dear editor, the novel coronavirus disease (covid-19) has rapidly spread across the world and caused a pandemic, and still continues to evolve. in iran, the first cases of covid-19 were officially announced between february 19 and 23, 2020 and it soon became clear that iran is one of the countries that is worst-hit by covid-19 outbreak (1, 2). it is now evident that most cases of covid-19 disease develop mild respiratory and constitutional symptoms (3), while some cases are asymptomatic (3, 4). involvement of other organs, including liver and kidneys has been reported in patients with covid-19 (5). many questions remain unanswered about associations and presentations of covid-19. shohada-e-tajrish hospital, a university hospital located in tehran, iran, was designated as one of the main centers providing diagnostic and healthcare services for patients suspected to be infected with the new virus. here, we share our experience regarding computed tomography (ct) findings suggestive of covid-19 disease among patients who underwent radiologic investigation due to traumatic injuries. several trauma patients had findings on their chest and/or abdominal ct scans, which were suggestive or highly suggestive of covid-19 (1). the findings were noted in the lung bases that were visible on an abdominal ct scan or on a clinically indicated spiral ct scan of the chest. the most frequent mechanisms of injury were fall and car accident. conscious patients did not report dizziness or loss of consciousness before the trauma and most of them did not have any symptoms related to covid-19 (e.g., fever, shortness of breath). to our knowledge, there is no study or report about the possible association between covid-19 and trauma in the lit∗corresponding author: morteza sanei taheri; department of radiology, shohada hospital, tajrish sq., tehran, iran. postal code: 1445613131, phone: 00982122739200, email: saneim@gmail.com erature. so, the mentioned observations could be just a coincidence, but this association could still be proposed as a research objective. the importance of this finding is that ct characteristics of covid-19 could be seen in patients who were admitted to the hospitals not due to covid-19 related symptoms, but because of chest and abdominal trauma. this issue should be considered by health care workers serving trauma patients and it should be kept in mind that during an outbreak of respiratory infections, in particular covid-19 disease, every attempt should be made to protect the health and safety of the staff even when providing care for trauma patients. 1. declarations 1.1. acknowledgements none. 1.2. author’s contribution mst developed the concept. mkh, ra, ez, ym, and hh prepared the draft of the letter. mst revised the letter. authors orcids mehdi khazaei: 0000-0001-7852-7951 reyhaneh asgari: 0000-0002-2052-2987 ehsan zarei1 orcid: 0000-0001-8529 yashar moharramzad: 0000-0002-5986-3754 hamidreza haghighatkhah: 0000-0001-5411-0609 morteza sanei taheri: 0000-0002-8881-9058 1.3. conflict of interest none. 1.4. funding and support no fund was received to prepare this letter. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. khazaei et al. 2 references 1. mahdavi a, khalili n, davarpanah ah, faghihi t, mahdavi a, haseli s, et al. radiologic management of covid-19: preliminary experience of the iranian society of radiology covid-19 consultant group (isrcc). iranian journal of radiology. (in press). 2. national committee on covid-19 epidemiology. daily situation report on coronavirus disease (covid-19) in iran; march 13, 2020. archives of academic emergency medicine. 2020;8(1):e23. 3. wu z, mcgoogan jm. characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72 314 cases from the chinese center for disease control and prevention. jama. 2020. 4. hu z, song c, xu c, jin g, chen y, xu x, et al. clinical characteristics of 24 asymptomatic infections with covid-19 screened among close contacts in nanjing, china. science china life sciences. 2020:1-6. 5. zhang c, shi l, wang f-s. liver injury in covid-19: management and challenges. the lancet gastroenterology & hepatology. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 70 emergency (2015); 3 (2): 70-74 original research comparison of intravenous metoclopramide and acetaminophen in primary headaches: a randomized controlled trial gholamreza faridaalaee1, seyed hesam rahmani1, hamidreza mehryar1, shahab bina shishavan*1, seyedeh zahra merghati2, mohammad amin valizade hasanloei3, bahman naghipour4, farzad rahmani5 1. department of emergency medicine, faculty of medicine, urmia university of medical sciences, urmia, ir iran. 2. department of internal surgery, school of nursing and midwifery, international branch of urmia university of medical sciences, urmia, ir iran. 3. department of anesthesiology, urmia university of medical sciences, urmia, ir iran. 4. department of anesthesiology, tabriz university of medical sciences, tabriz, ir iran. 5. department of emergency medicine, tabriz university of medical sciences, tabriz, iran. *corresponding author: bina shishavan shahab, department of emergency medicine, imam khomeini hospital, ershad avenue, urmia, iran. tel: +989141889486; fax: +984433457286; email: shahabbina@gmail.com received: september 2014; accepted: november 2014 abstract introduction: headache is the most common neurologic symptom among referees to the emergency department (ed), while the best treatment has not yet been found. therefore, in the present study pain relief effects of metoclopramide and acetaminophen were compared in patients suffered acute primary headache. methods: this study was a double-blind randomized clinical trial performed in imam khomeini hospital, urmia, iran, through july to october 2014. all adult patients, with acute primary (migraine, tension type and cluster) headache referred to the ed were included in this study. pain severity was measured with 10 centimeters numeric rating scales. the patients were randomized into two groups of intravenous (iv) metoclopramide (10 milligrams) and acetaminophen (1 gram). pain score, success rate, and drug complications were compared between the 2 groups at 0, 15, 30, 60, and 120 minutes after injection. results: 100 patients were equally categorized into two groups (mean age of 32 ± 13.2 years; 51.2% male). initial pain score in metoclopramide and acetaminophen groups were 9.1 and 9.4, respectively (p = 0.46). iv metoclopramide did not have any analgesic effect at 15 minutes, but had good effect at 30 minutes. while, the analgesic effect of acetaminophen initiated after 15 minutes. after 2 hours, both drugs had good therapeutic effect on primary headaches (p < 0.001). conclusion: the present study demonstrated that efficacy of metoclopramide for pain relief in primary headaches is lower than acetaminophen. in this regard, success rate of acetaminophen was 42.0% versus 0% for metoclopramide within 15 minutes. the efficacy of acetaminophen continued until 60 minutes. key words: metoclopramide; acetaminophen; headache; migraine; acute pain cite this article as: faridaalaee g, rahmani sh, mehryar h, et al. comparison of intravenous metoclopramide and acetaminophen in primary headaches: a randomized controlled trial. emergency. 2015;3(2):70-4. introduction: headache is one of the most common neurologic symptoms among patients admitted to the emergency department (ed), as 3 million patients are annually visited only in the eds of united states (1, 2). the disease is categorized into primary (such as migraine, tension type, and cluster) and secondary (such as those following intracerebral hemorrhage, trauma, tumor, etc.) groups. primary is the most frequent type seen in eds and 90% of them include migraine, tension, or even a combination of them (3, 4). approximately, 12% of general population suffer from migraine and acute exacerbations cause severe and disabling disorders (5-7). several agents such as nonsteroidal anti-inflammatory drugs (nsaids), opioids, antiemetics, antipsychotics, etc. have been used for treatment (8). recently, the use of dopamine antagonists, such as metoclopramide (alone or in combination with other drugs), and serotonin agonists, like sumatriptan, for this purpose has increased (9, 10). administration of metoclopramide relieves the intensity of headaches; however, its efficacy varies among studies. for example, while, tec et al. declared an acp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 71 emergency (2015); 3 (2): 70-74 ceptable therapeutic effect for metoclopramide in primary headaches, coppola et al. deemed its efficacy to be equal to placebo (4, 11, 12). given the above results, evaluation of metoclopramide’s efficacy in management of primary headaches requires more studies to derive a concrete and clear conclusion. therefore, the present study aimed to compare analgesic effects of intravenous (iv) metoclopramide and acetaminophen for acute primary headaches. methods: study design and setting this study was a double-blind randomized clinical trial performed in imam khomeini hospital, urmia, iran, through july to october 2014. the effect of iv metoclopramide (10 milligrams) and acetaminophen (1 gram) in treatment of acute headaches was compared. for ethical reasons, there was no placebo arm. the study protocol was confirmed by ethical committee of urmia university of medical sciences and informed consent was obtained from patients. this protocol was registered in iranian registry of clinical trials with irct number: irct2014081817812n3. subjects patients with acute primary headache and pain severity over 4 based on numeric rating scale (nrs), who were referred to the ed and did not have any systematic disease, were included. exclusion criteria were having allergy to metoclopramide and acetaminophen, hepatic failure, secondary headache, pregnancy, breast-feeding, renal insufficiency, arbitrary treatment, and the case of recurrent headache. migraine, tension type, and cluster headaches were diagnosed based on international headache society’s international classification of headache disorders (ichd) criteria (13). intervention the patients were randomized into two groups of metoclopramide (intervention group) with dosage of 10 milligrams, iv, in 2 minutes and acetaminophen group (control group) with dosage of 1 gram, slow iv, in 10 minutes. randomization was performed by block randomization (size of 5 for blocks), using an online random number generator (rng). solutions were prepared by an independent pharmacist and kept in a sealed envelope. drugs were injected by a physician blinded to the studied groups. response to treatment and the side effects were assessed within 15, 30, 60, and 120 minutes after receiving medications and then compared with the baseline. the ed staff were blinded to composition of solutions and studied groups. the data of the prescribed solution were only available for the staff when drug complications and other adverse effects appeared in patients and the patient was excluded from the study. rescue dose was prescribed, if the pain continued after 30 minutes from first drug administration. the disclosure of the data about the prescribed medicine(s) was not required during the study period. measurements 11-scale standard numeric rating scale (nrs) was used to assess the pain score of patients (14). patients were given a score number between 0 and 10, 0 representing no pain and 10 demonstrating the worst conceivable pain. pain severity was assessed in the baseline (administration time) and then reassessed 15, 30, 60, and 120 minutes after medication. this follow up was performed because 120 minutes is a more standard endpoint for outpatient migraine trials (15). nausea, vomiting, vertigo, and lethargy were recorded as adverse effects based on self-reports and clinical manifestations. therapeutic success rate was defined as decreasing pain score to at least 3. statistical analysis the minimum required sample size for the present study considering the clinically significant change of 2 scores in pain severity, standard deviation of 2.7 and 1.2 centimeters for effects of metoclopramide and acetaminophen in decreasing headache, power of 90% (β=0.1) and the error rate of 5% (α=0.05) was estimated to be 33 subjects (16, 17). data were analyzed using spss 21. quantitative variables were reported as mean and standard deviation and qualitative ones as frequency and percentage. chisquare and fisher exact tests were also used for comparison of basic characteristics of the two groups. because data was not normally distributed, the comparison between pain severity changes in patients was performed using wilcoxon-rank test. the success rate was reported as frequency and percentage as well as comparison of time changes between two therapies performed by nonparametric test for trend, which is an extension model of the wilcoxon rank-sum test. since some basic features between two therapeutic groups had significant difference, general linear model was done to find if success rate had significant difference after moderating these factors. p < 0.05 was considered as a significant level. results: 100 patients were equally categorized into two groups of iv acetaminophen and metoclopramide (mean age of 32 ± 13.2 years; 51.2% male). table 1 shows demographic data of patients. as can be seen, age distribution of the two groups was significantly different (p < 0.001). most migraine sufferers received iv acetaminophen, while patients with tension headache mostly took metoclopramide (table 1, p < 0.001). the pain severity at administration time had no difference between the groups (p = 0.46). however, the mean pain severity at 15 minutes after taking acetaminophen was significantly less than metoclopramide group (7.0 ± 1.4 versus 9.0 ± 1.3, p < 0.001). this pattern was seen within 30 minutes (4.5 ± 2.0 versus 6.6 ± 1.5; p < 0.001), 60 minutes (3.1 ± 2.1 versus 5.4 ± 1.6; p < 0.001), and even 120 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com faridaalaee et al 72 minutes (3.6 ± 2.0 versus 1.5 ± 1.2; p < 0.001) after injection (table 2). 21 (42%) patients in acetaminophen group had significant pain relief, while none of subjects in metoclopramide group had such effectiveness in 15 minutes after medication. the 30-minute success rate for acetaminophen and metoclopramide groups were 100% and 74%, respectively. 100% therapeutic success rate in iv acetaminophen remained until 120 minutes (table 2, p = 0.001). no side effect was seen among patients. only 3 (6%) patients of metoclopramide group needed the rescue dose. after adjustment of analysis for basic characteristics, the rate of therapeutic success for iv acetaminophen at 15 minutes (or=1.43; 95% cl=1.2-1.7; p < 0.001), 30 minutes (or=1.38; 95%cl=1.17-1.64; p < 0.001), and 60 minutes (or=1.10; 95% cl=1.01-1.26; p = 0.04) was more than metoclopramide (table 3). discussion: based on the present study and similar to other major studies, metoclopramide had a pain relief effect on primary headaches, but in contrast to other researches, here metoclopramide had inferior effect to acetaminophen. it can be justified under racial differences. several studies have been performed regarding therapeutic effects of metoclopramide on the primary headaches with table 1: comparison of demographic data between two studied groups variable acetaminophen metoclopramide p1 age (year) <18 7 (43.8) 9 (56.2) <0.001 18-40 43 (67.2) 21 (32.8) 41-60 0 (0.0) 18 (100.0) 61-75 0 (0.0) 2 (100.0) gender male 22 (51.2) 21 (48.8) female 28 (49.1) 29 (50.9) 0.84 marital status single 15 (53.6) 13 (46.4) 0.66 married 35 (48.6) 37 (51.4) type of headache migraine 35 (67.3) 17 (32.7) tension type 8 (23.5) 26 (76.5) <0.001 cluster 7 (50.0) 7 (50.0) 1, based on chi-squared test; 2, based on fisher exact test. table 2: comparison of pain score and successes rate in medical interventions between studied groups time (minute) acetaminophen metoclopramide p1 mean ± sd success rate (%) mean ± sd success rate (%) baseline 9.4 ± 0.7 --- 9.1 ± 1.3 ---0.46 15 7.0 ± 1.4 21 (42.0) 9.0 ± 1.3 0 (0.0) <0.001 30 4.5 ± 2.0 50 (100.0) 6.6 ± 1.5 34 (74.0) <0.001 60 3.1 ± 2.1 50 (100.0) 5.4 ± 1.6 47 (94.0) <0.001 120 1.5 ± 1.2 50 (100.0) 3.6 ± 2.0 50 (100.0) <0.001 1, based on kruskal-wallis equality of populations rank test; sd: standard deviation. table 3: results of multivariate analysis for comparison of success rate between two groups time (minute) odds ratio 95% ci p1 15 1.43 1.21-1.73 <0.001 30 1.38 1.17-1.64 <0.001 60 1.10 1.01-1.26 0.04 1, based on general linear model adjusted for age and type of headache; ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 73 emergency (2015); 3 (2): 70-74 different results. while some of them showed good efficacy of metoclopramide for primary headaches, others concluded no efficacy. salazar-zúñiga and garfias-arvizu compared metoclopramide and sumatriptan in migraine sufferers and demonstrated that metoclopramide is more effective (18). tec et al. showed that metoclopramide has therapeutic effects on headache, alone (4). coppola et al. compared prochlorperazine, metoclopramide, and placebo; they showed that prochlorperazine has therapeutic effects on headache, but metoclopramide is more effective than placebo (9). in contrast, cameron et al. compared prochlorperazine and metoclopramide, and demonstrated that prochlorperazine and metoclopramide are both effective on acute migraine headaches (19). colman et al. concluded that metoclopramide is effective on the migraine especially in combination with other agents (20). friedman et al. stated that a combination of metoclopramide and diphenhydramine are more effective than ketorolac for headaches (21). in another study, friedman et al. compared 10 milligrams of iv prochlorperazine and combination of 20 milligrams metoclopramide and 25 milligrams diphenhydramine for acute migraine headaches. they showed prochlorperazine and combination of metoclopramide and diphenhydramine have the same effect for acute migraine headaches (22). in another study, friedman et al. displayed 10 metoclopramide are more efficient than 30 milligrams ketorolac or 1000 milligrams valproate sodium (23). weinman et al. performed a systemic review to find an effective drug for tension type of headaches and reviewed 8 studies. their results were as below: metamizole, chlorpromazine, and metoclopramide are more effective than placebo for acute pain. the combination of metoclopramide with diphenhydramine has superiority to ketorolac. mepivacaine, meperidine with promethazine, and sumatriptan are not more effective than placebo (24). the results of this study had some similarities and dissimilarities with other studies. variances in regimens and doses of medications can result in different efficacy of medications, so that use of one standard regimen may lead to results that are more coherent. extrapyramidal reactions are one of the most important side effects of metoclopramide, which have been reported in nearly 10% of cases. for example, coppola et al. demonstrated 2.5% of patients displayed dystonia or akathisia in initial minutes of drug administration (12). also friedman et al. stated that akathisia developed in 9.3% of patients (25). however, no side effect was found in the present study. there were several limitations in this study. the first limitation was the short follow-up period. although, during 2 hours follow up no side effect was observed, the longer period such as 1or 2 days and even 1week follow up might have provided a better opportunity to evaluate long-term side effects and headache recurrence. another limitation was single-blinded design of the trial. we were unable to do the study in a double-blinded way, because the routes of administration for drugs were different. moreover, the lack of a placebo group or standard arm due to ethical consideration was also considered as another limitation. conclusion: the present study demonstrated that efficacy of metoclopramide in pain relief of headaches is lower than acetaminophen. in this regard, success rate of acetaminophen in pain relief was 42.0%, while it was 0% for metoclopramide within 15 minutes. the efficacy of acetaminophen continued until 60 minutes. acknowledgments: all authors would like to say thanks to all staff of imam khomeini hospital and the research center of urmia university of medical sciences. conflict of interest: none funding support: this study was granted by the research center of urmia university of medical sciences, grant number: 1872143-25 authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. taylor fr. diagnosis and classification of headache. prim care. 2004;31(2):243-59. 2. mccaig lf, nawar ew. national hospital ambulatory medical care survey: 2004 emergency department summary: us department of health and human services, centers for disease control and prevention, national center for health statistics; 2006. p. 372. 3. friedman bw, hochberg ml, esses d, et al. applying the international classification of headache disorders to the emergency department: an assessment of reproducibility and the frequency with which a unique diagnosis can be assigned to every acute headache presentation. ann emerg med. 2007;49(4):409-19. 4. tek ds, mcclellan ds, olshaker js, allen cl, arthur dc. a prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department. ann emerg med. 1990;19(10):1083-7. 5. diamond s, bigal me, silberstein s, loder e, reed m, lipton rb. patterns of diagnosis and acute and preventive treatment for migraine in the united states: results from the american migraine prevalence and prevention study. headache. 2007;47(3):355-63. 6. goadsby pj, lipton rb, ferrari md. migraine—current understanding and treatment. n engl j med. 2002;346(4):25770. 7. wood aj, goadsby pj, lipton rb, ferrari md. migraine— current understanding and treatment. n engl j med. 2002;346(4):257-70. 8. vinson dr. treatment patterns of isolated benign headache in us emergency departments. ann emerg med. 2002;39(3):215-22. 9. coppola m, yealy dm, leibold ra. randomized, placebo this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com faridaalaee et al 74 controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. ann emerg med. 1995;26(5):541-6. 10. talabi s, masoumi b, azizkhani r, esmailian m. metoclopramide versus sumatriptan for treatment of migraine headache: a randomized clinical trial. j res med sci. 2013;18(8):695. 11. ashina s, portenoy rk. intravenous treatment of migraine. tech reg anesth pain manag. 2012;16(1):25-9. 12. coppola m, yealy dm, leibold ra. randomized, placebocontrolled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. annals of emergency medicine. 1995;26(5):541-6. 13. olesen j, steiner t. the international classification of headache disorders, 2nd edn (icdh-ii). j neurol neurosurg psychiatry. 2004;75(6):808-11. 14. todd kh, funk kg, funk jp, bonacci r. clinical significance of reported changes in pain severity. ann emerg med. 1996;27(4):485-9. 15. tfelt‐hansen p, block g, dahlöf c, et al. guidelines for controlled trials of drugs in migraine. cephalalgia. 2000;20(9):765-86. 16. turkcuer i, serinken m, eken c, et al. intravenous paracetamol versus dexketoprofen in acute migraine attack in the emergency department: a randomised clinical trial. emerg med j. 2014:182-5. 17. colman i, friedman bw, brown md, et al. parenteral dexamethasone for acute severe migraine headache: metaanalysis of randomised controlled trials for preventing recurrence. bmj. 2008;336(7657):1359-61. 18. salazar-zúñig a, garfias-arvizu a. management of the acute migraine episode with sumatriptan vs. metoclopramide. rev biomed. 2006;17:175-82. 19. cameron jd, lane pl, speechley m. intravenous chlorpromazine vs intravenous metoclopramide in acute migraine headache. acad emerg med. 1995;2(7):597-602. 20. colman i, brown md, innes gd, grafstein e, roberts te, rowe bh. parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials. bmj. 2004;329(7479):1369-73. 21. friedman bw, adewunmi v, campbell c, et al. a randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches. ann emerg med. 2013;62(4):311-8. e4. 22. friedman bw, esses d, solorzano c, et al. a randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. ann emerg med. 2008;52(4):399406. 23. friedman bw, garber l, yoon a, et al. randomized trial of iv valproate vs metoclopramide vs ketorolac for acute migraine. neurology. 2014;82(11):976-83. 24. weinman d, nicastro o, akala o, friedman bw. parenteral treatment of episodic tension-type headache: a systematic review. headache. 2014;54(2):260-8. 25. friedman bw, mulvey l, esses d, et al. metoclopramide for acute migraine: a dose-finding randomized clinical trial. ann emerg med. 2011;57(5):475-82.e1. emergency. 2018; 6 (1): e10 or i g i n a l re s e a rc h dexmedetomidine-fentanyl versus midazolam-fentanyl in pain management of distal radius fractures reduction; a randomized clinical trial ali arhami dolatabadi1∗, elham memary2, majid shojaee1, hossein kamalifard1 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. anesthesiology department, imam hossein hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. received: december 2017; accepted: january 2018; published online: 20 january 2018 abstract: introduction: currently, using various combinations of sedative and analgesic agents has received attention for induction of sedation and analgesia due to their synergy in controlling pain and anxiety. the present study was designed with the aim of comparing dexmedetomidine-fentanyl combination with midazolam-fentanyl in this regard. methods: in this randomized clinical trial, patients diagnosed with distal radius fracture who had visited the emergency department (ed) were allocated to either the group receiving the combination of fentanylmidazolam or the one receiving dexmedetomidine-fentanyl for procedural sedation and analgesia (psa) and were compared regarding analgesic characteristics, time to recovery and side effects. results: 80 patients with the mean age of 42.08 ± 12.17 (18 60) years were randomly allocated to 2 groups of 40 (83.80% male). the 2 groups did not have a significant difference regarding baseline characteristics as well as pain severity. mean pain score at the time of procedure was 3.47 ± 1.37 in dexmedetomidine and 2.85 ± 1.05 in midazolam group (p = 0.025). in addition, time to recovery in dexmedetomidine and midazolam groups was 6.60 ± 1.86 minutes and 12.70 ± 1.70 minutes, respectively (p < 0.001). out of the 9 patients who experienced treatment failure, 8 (88.90%) patients were in dexmedetomidine group and 1 (11.10%) was in midazolam group (p = 0.029). absolute risk increase rate of treatment failure in case of using dexmedetomidine instead of midazolam was 17.50% (95%ci: 4.19 – 30.81) and number needed to harm was 6.00 (95% ci: 3.20 – 23.80). conclusion: although the combination of dexmedetomidine-fentanyl had a shorter time to recovery compared to midazolam-fentanyl for induction of sedation and analgesia, the treatment failure rate in case of using dexmedetomidine with 1 µg/kg increased 17.5% and about 1 out of each 6 patients needed a rescue dose. keywords: conscious sedation; analgesia; dexmedetomidine; midazolam; closed fracture reduction; clinical trial © copyright (2018) shahid beheshti university of medical sciences cite this article as: arhami dolatabadi a, memary e, shojaee m, kamalifard h. dexmedetomidine-fentanyl versus midazolam-fentanyl in pain management of distal radius fractures reduction; a randomized clinical trial. emergency. 2018; 6(1): e10. 1. introduction d istal radius fracture is among the common orthopedic problems and preserving the function of the joint by reduction, anatomic correction and fixating under sedation and analgesia are the priorities of treating these patients in emergency department (ed) (1). for reducing pain at the time of reduction, various methods exist including nerve block (2), hematoma block (3), and induction of se∗corresponding author: ali arhami dolatabadi; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. email: aliarhami@yahoo.com tel: 00989122847642 dation and analgesia using various drug compounds available to the physicians handling these patients (4, 5). fewer side effects on the respiratory system and hemodynamic status are among the characteristics desired by emergency physicians when selecting a drug for use in induction of sedation and analgesia. currently, using various combinations of sedative and analgesic agents has received attention in this regard due to their synergy in controlling pain and anxiety. for this purpose, the combination of midazolam and fentanyl, as a powerful and short acting synthetic opiate and a fast acting benzodiazepine with a short halflife, respectively, has been very desirable and frequently used among emergency medicine specialists (6, 7). on the other this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. arhami dolatabadi et al. 2 hand, dexmedetomidine as a central alpha-2 agonist that has received the official approval of american food and drug administration (fda) in 1999 and has sympatholytic, antianxiety, pain relief, and analgesic effects has been considered for induction of conscious sedation (8). findings of various studies on comparison of the sedative effects of dexmedetomidine and midazolam is indicative of their difference regarding time of recovery and side effects on the respiratory system and hemodynamics (9, 10). although a study by vazquez et al. indicated that the time to recovery of midazolam was twice the time to recovery of dexmedetomidine (11), another study by zeyneloglu et al. showed completely reversed results (12). it seems that dexmedetomidine will have a more successful performance compared to midazolam in cases that sedation is required for airway procedures such as bronchoscopy (13). therefore, the present study was designed and performed with the aim of comparing dexmedetomidine and fentanyl combination with midazolam and fentanyl combination in induction of sedation and analgesia for reduction of distal radius fracture in the ed. 2. methods 2.1. study design and setting in the present single blind randomized clinical trial, patients diagnosed with distal radius fracture who had visited the ed of imam hossein and hafte tir hospitals, tehran, iran, were studied. the patients were allocated to either the group receiving the combination of fentanyl and midazolam (midazolam group) or the one receiving dexmedetomidine and fentanyl (dexmedetomidine group) for induction of sedation and analgesia for reducing the fracture and the characteristics of the 2 combinations were compared. this study was approved by the ethics committee of faculty of medicine, shahid beheshti university of medical sciences and was registered on the iranian registry of clinical trials (irct) under the number irct20160401027165n1. the researchers adhered to ethical principles and confidentiality of patient data throughout the study. informed consent was obtained from the patients for participating in the study. 2.2. participants all the patients with distal radius fractures who had presented in the working shifts of the senior resident in charge of the study (including morning and night shifts in both weekdays and holidays) and aged between 18 and 60 years were included in the study without any sex limitations and using non-probability consecutive sampling. patients who had a history of using antihypertensive or antihistamine medications, patients with head trauma and loss of consciousness, severe chest trauma, cervical vertebra trauma with unstable fracture, mental retardation, those who could not verbally communicate, hemodynamically unstable patients, those with a history of allergic reaction to drugs, addicts and those who had a history of drug abuse, pregnant women, and those with a history of cardiac disease (cardiac block and bradycardia) were excluded from the study. 2.3. intervention after selecting the patients meeting the inclusion criteria, the participants were randomly allocated to one of the study groups. after establishment of proper peripheral vein, cardiac monitoring, pulse oximetry, blood pressure monitoring and preparing complete equipment for cardiopulmonary resuscitation on the patients’ bedside, attempts were made to induce sedation and analgesia at the level of conscious sedation. the patient and the person who was responsible for statistical analysis were blind to the type of drug used. a trained nurse was in charge of preparing the 2 drug compounds used in separate syringes looking the same. in addition, a senior emergency medicine resident was in charge of the study and data gathering under the supervision of an emergency medicine specialist. we cannot be sure of the blinding of the person gathering data to the type of treatment received, due to the difference in the method of injecting midazolam and dexmedetomidine and not performing double dummy blinding. in this study, dose of dexmedetomidine (huspiria of usa, behestan phamaceutical co, iran) was considered 1µg/kg and was injected during 10 minutes in 100cc normal saline. in addition, midazolam (darupakhsh co, iran) with dose of 0.01 mg/kg was administered via slow and titrated intravenous injection. fentanyl (abu ravihan co, iran) was prescribed with 3 µg/kg body weight dose for both groups and was administered via slow intravenous injection. pain severity of the patients was measured and recorded using visual analogue scale (vas) once before administration of the drugs and once before performing the procedure (10-15 minutes after drug administration). a score of 10 was considered the worst pain score and 0 was the lowest score. at least 3 points decrease in pain severity 10-15 minutes after receiving the drug was considered as treatment success and not decreasing as much was considered treatment failure. in case the pain did not decrease in a maximum of 15 minutes after drug injection, another injection was done using fentanyl with 3 µg/kg body weight dose but these patients were not excluded from the final analysis. 2.4. data gathering to gather data, a designed checklist consisting of age, sex, pain severity before intervention and 15 minutes after receiving the drug, duration of procedure, time to recovery, and probable side effects (apnea, nausea and vomiting, hypotension, and bradycardia) was used. the person in charge of data gathering was a senior emergency medicine resident this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e10 table 1: comparison of age and sex distribution of the participants in the 2 studied groups variables group n (%) p dexmedetomidine/fentanyl midazolam/fentanyl sex male 33 (85.0) 34 (82.5) 0.762 female 7 (15.0) 6 (17.5) age (year) 18-45 16 (40.0) 9 (22.5) 45-55 5 (12.5) 11 (27.5) 0.120 55 ≤ 19 (47.5) 20 (50.0) table 2: comparing mean pain severity at the time of reduction initiation (15 minutes after sedation), mean procedure duration and mean time to recovery between the 2 studied groups variable groups p dexmedetomidine midazolam response to treatment 32 (80.0) 39 (97.5) 0.029 treatment failure 8 (20.0) 1 (2.5) pain severity at the time of reduction 3.47 ± 1.37 2.85 ± 1.05 0.025 procedure duration (minutes) 12.57 ± 1.75 12.60 ± 1.78 0.950 time to recovery 6.60 ± 1.86 12.70 ± 1.70 < 0.001 pain severity according to visual analogue scale. data were presented as mean ± standard deviation or number (%). under the supervision of an emergency medicine specialist. the duration of procedure was considered from the initiation of reduction until the end of fixating the reduced bone. in addition, time to recovery was considered the time interval between the end of the procedure until complete regain of consciousness and awakening of the patient 2.5. statistical analysis for analyzing data, spss 21 statistical software was used. for reporting data, frequency and percentage, or mean ± standard deviation were used. minimum required sample size for performing the study was determined as 40 patients in each group considering type 1 error of 5%, 95% power, 96% and 67% probability of failure for the 2 groups (12) and the minimum clinically significant difference of 30%. to compare the results between the 2 groups, statistical tests including ttest, chi-square, and fisher’s exact test were applied. in addition, the rate of absolute risk increase and number needed to harm of treatment failure in case of using dexmedetomidine instead of midazolam was calculated using a medical calculator and reported. level of significance was considered to be 5%. 3. results 3.1. baseline characteristics of the patients 80 patients with the mean age of 42.08 ± 12.17 (18 60) years were randomly allocated to 2 groups of 40 and studied (83.80% male). table 1 compares the age and sex distribution of the patients in the 2 groups. mean age in dexmedetomidine group was 40.65 ± 13.25 and it was 43.52 ± 10.95 years in midazolam group (p = 0.294). all the studied patients had a pain severity equal to or greater than 6 in the beginning of reduction. mean pain severity in dexmedetomidine and midazolam groups before reduction was 8.28 ± 1.13 and 8.18 ± 1.08, respectively (p = 0.688). 3.2. response to treatment overall, 71 (88.80%) patients experienced 3 points decrease in pain score after receiving the drug. out of the 9 patients who experienced treatment failure, 8 (88.90%) patients were in dexmedetomidine group and 1 (11.10%) was in the midazolam group (p = 0.029). table 2 compares mean pain severity at the time of reduction, mean duration of reduction and mean time to recovery between the 2 groups. mean pain score at the time of reduction was not significantly different between the 2 groups from a clinical point of view; however, dexmedetomidine group had a significantly shorter time to recovery (p < 0.001). none of the patients in either group experienced any special side effects including apnea, nausea and vomiting, or hypotension. only 3 (7.5%) patients in dexmedetomidine group experience a short episode of bradycardia, which was resolved by slowing the infusion rate from 10 minutes to 15-20 minutes without hemodynamic impairment. absolute risk increase rate of treatment failure in case of using dexmedetomidine instead of midazolam was 17.50% (95%ci: 4.19 – 30.81) and number needed to harm was 6.00 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. arhami dolatabadi et al. 4 (95% ci: 3.20 – 23.80). 4. discussion based on the results of the present study, although the combination of dexmedetomidine and fentanyl had a shorter time to recovery compared to midazolam and fentanyl for induction of sedation and analgesia, the treatment failure rate in case of using dexmedetomidine with 1 µg/kg increased 17.5% and about 1 out of each 6 patients needed a rescue dose. after approval of dexmedetomidine as a sedative drug, various studies have been done regarding the effectiveness of this drug and comparing it to other sedative drugs. a comparison between this drug and propofol has indicated the similar sedative effects of both drugs despite the lower effect of dexmedetomidine on the respiratory system and hemodynamics (14, 15). senoglu et al. in a clinical trial on 40 patients in need of sedation for non-invasive ventilation, prescribed midazolam for 1 group and dexmedetomidine for the other. their findings indicated the equal sedative effects of both drugs; however, the group that received dexmedetomidine needed less dose adjustment in comparison to midazolam (16). dexmedetomidine has been successfully used in providing a conscious sedation state without any respiratory distress and hemodynamic instability throughout fiberoptic bronchoscopy (17). zeyneloglu et al. compared dexmedetomidine with midazolam/fentanyl combination in inducing sedation for extracorporeal shock wave lithotripsy (eswl) and showed that the group receiving dexmedetomidine needed more rescue doses and also more time to recovery (12). however, the findings of the present study were in line with the mentioned one regarding more need for rescue doses; however, they do not agree regarding time to recovery. in addition, vazquez et al. compared midazolam and dexmedetomidine for induction of sedation for endoscopy of the upper digestive system and indicated that the group that received dexmedetomidine had a significantly shorter time to recovery and higher satisfaction. in this study, no difference was reported between the 2 drugs regarding side effects and sedative properties (11). the findings of this study was in agreement with the results of the present study, yet as reported in the results section, the patients receiving dexmedetomidine had a significantly higher rate of treatment failure and more need for a rescue dose. regarding the side effects of these drugs on respiratory system and hemodynamics there isn’t much of an agreement between the studies. although the findings of the study by frolich et al. indicate the superiority of midazolam for having less effect on the mentioned systems (10), shukry et al. believe that when less effect on the airway and need for faster awakening are priorities for the in-charge physician and the patient, dexmedetomidine seems to be a proper choice (9). the reason for these differences could be the different ethnic characteristics of the studied patients, different areas in which the drugs were used, different doses of drugs, different drug compounds and. . . . however, there is not much experience regarding use of dexmedetomidine specially in ed and for induction of sedation and analgesia and to reach a final decision on points such as time to recovery, side effects of the drug on hemodynamics and respiratory system as well as success and failure rates, further studies are required. performing multi-center studies with a big sample size and considering all the principles of clinical trials might help in this regard. 5. limitation not using double dummy blinding and the probability of the person gathering data being aware of the drugs used can be mentioned as the most important limitations of this study. additionally, not following patients regarding probable digestive and other side effects during the hours after sedation are among other limitations of the present study. 6. conclusion based on the results of the present study, although the combination of dexmedetomidine and fentanyl had a shorter time to recovery compared to midazolam and fentanyl for induction of sedation and analgesia, the treatment failure rate in case of using dexmedetomidine with 1 µg/kg increased 17.5% and about 1 out of each 6 patients needed a rescue dose. 7. appendix 7.1. acknowledgements we would like to thank all the ed staff who participated in this study. 7.2. authors’ contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support none declared. 7.4. conflict of interest none declared. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e10 references 1. diaz-garcia rj, oda t, shauver mj, chung kc. a systematic review of outcomes and complications of treating unstable distal radius fractures in the elderly. the journal of hand surgery. 2011;36(5):824-35.e2. 2. hossein a, majid s, mehdi s, somayeh a, ali v, alireza m. nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial. emergency (tehran, iran). 2013;1(1):11-4. 3. myderrizi n, mema b. the hematoma block an effective alternative for fracture reduction in distal radius fractures. medical archives. 2011;65(4):239. 4. schofield s, schutz j, babl fe. procedural sedation and analgesia for reduction of distal forearm 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2001;14(1):13-21. 9. shukry m, miller ja. update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures. therapeutics and clinical risk management. 2010;6:111. 10. frolich ma, arabshahi a, katholi c, prasain j, barnes s. hemodynamic characteristics of midazolam, propofol, and dexmedetomidine in healthy volunteers. journal of clinical anesthesia. 2011;23(3):218-23. 11. vazquez-reta j, jimenez fm, colunga-sanchez a, pizarro-chavez s, vazquez-guerrero a, vazquezguerrero a. midazolam versus dexmedetomidine for sedation for upper gastrointestinal endoscopy. revista de gastroenterologia de mexico. 2011;76(1):13-8. 12. zeyneloglu p, pirat a, candan s, kuyumcu s, tekin i, arslan g. dexmedetomidine causes prolonged recovery when compared with midazolam/fentanyl combination in outpatient shock wave lithotripsy. european journal of anaesthesiology. 2008;25(12):961-7. 13. goneppanavar u, magazine r, periyadka janardhana b, krishna achar s. intravenous dexmedetomidine provides superior patient comfort and tolerance compared to intravenous midazolam in patients undergoing flexible bronchoscopy. pulmonary medicine. 2015;2015:8. 14. venn r, grounds r. comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. british journal of anaesthesia. 2001;87(5):684-90. 15. mahmoud m, gunter j, donnelly lf, wang y, nick tg, sadhasivam s. a comparison of dexmedetomidine with propofol for magnetic resonance imaging sleep studies in children. anesthesia & analgesia. 2009;109(3):745-53. 16. senoglu n, oksuz h, dogan z, yildiz h, demirkiran h, ekerbicer h. sedation during noninvasive mechanical ventilation with dexmedetomidine or midazolam: a randomized, double-blind, prospective study. current therapeutic research. 2010;71(3):141-53. 17. bergese sd, khabiri b, roberts wd, howie mb, mcsweeney td, gerhardt ma. dexmedetomidine for conscious sedation in difficult awake fiberoptic intubation cases. journal of clinical anesthesia. 2007;19(2):141-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e12 le t t e r to ed i to r a novel coronavirus outbreak from wuhan city in china, rapid need for emergency departments preparedness and response; a letter to editor mostafa alavi-moghaddam1∗ 1. emergency medicine department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: february 2020; accepted: february 2020; published online: 2 february 2020 cite this article as: alavi-moghaddam m. a novel coronavirus outbreak from wuhan city in china, rapid need for emergency departments preparedness and response; a letter to editor. arch acad emerg med. 2020; 8(1): e12. dear editor on 31 december 2019, chinese authorities reported the increase in incidence of severe pneumonia in wuhan city, hubei province of china. one week later, on january 7th, they confirmed that they had identified a new coronavirus, which is a family of microrna respiratory viruses including the common cold, and viruses such as severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers). this new virus was temporarily named "2019-ncov". wuhan city is a major international transport hub. this report to world health organization (who), raised global public health concern because this is the third coronavirus âăşassociated acute respiratory illness outbreak. currently, up to the date of submitting this letter, 4593 cases of 2019-ncov infections have been confirmed globally, both in china (4537 have been confirmed, 976 of them presented with severe disease and 106 died) and outside of china (56 confirmed in 14 countries.). who risk assessment of 2019ncov infection is very high in china and high in other countries (1). although 2019-ncov has not been included in the who blueprint list of priority diseases yet, mers cov, and sars – cov, which are already included in this list, are both coronaviruses that have led to global outbreaks in 2003 and 2012, respectively. the specific source and the exact primary mode of transmission of 2019-ncov to humans remain unknown. the clinical features and laboratory and radiological abnormalities with 2019-ncov infections are not specific and are similar to other respiratory tract infections. adults and pediatrics who ac∗corresponding author: emergency medicine department, imam hossein hospital, madani avenue, imam hossein square, tehran, iran. email: mosalavi@sbmu.ac.ir, tel: 00989122967248 quire a 2019-ncov infection can show a spectrum of respiratory illness severity, from asymptomatic to mild, moderate or severe disease. the severe disease manifests as severe acute respiratory infection (sari) or severe pneumonia, acute respiratory distress syndrome (ards), sepsis and septic shock. patients with pre-existing medical comorbidities develop a more severe disease and have higher mortality rates compared to patients who do not have any comorbidity. clinical care of patients with suspected 2019-ncov should focus on early recognition, immediate isolation (separation), implementation of appropriate infection prevention and control (ipc) measures and provision optimized supportive care. at the triage of an emergency room, early recognition of suspected patients allows for timely initiation of ipc. 2019-ncov should be considered as a possible etiology of influenza like illness (ili) under certain situations according to case definitions of who (2). both the health care worker (hcw ) and the suspected case of acute respiratory illness (ali) should wear a medical mask and the patient should better be directed to a separate area, an isolation room if available. otherwise, keep a distance of at least one meter between suspected patients and other patients. instruct all suspected patients to cover their nose and mouth during coughing or sneezing with tissue or flexed elbows for protecting others. those with mild or moderate clinical presentations of the 2019-ncov infection may not require hospitalization, unless there is concern of rapid deterioration. all patients discharged to go home directly from fast track in emergency room should be instructed to consider ipc measures and to return hospital if their symptoms worsen (3). patients with severe illness, who are admitted to the emergency ward, should be transferred to the floor and if available to the icu ward as soon as possible. as long as they stay in emergency ward, they should be placed in single rooms or grouped together with those who have the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. alavi-moghaddam 2 same etiological or clinical diagnosis. limit patient movement within the center and ensure that patients wear medical masks when outside their rooms. hcw should perform hand hygiene after contact with respiratory secretions. droplet and contact precautions prevent direct or indirect transmission of the disease from contact with contaminated surfaces or equipment. hcw should use personal protective equipment (ppe) including medical mask, eye protection, gloves and gown, when entering the room and remove ppe when leaving. if equipment needs to be shared among patients, they should be cleaned and disinfected after each patient’s use. hcw should apply airborne precautions when performing an aerosol generating procedure (i.e. open suctioning of respiratory tract, intubation, bronchoscopy, cardiopulmonary resuscitation) (4). hcw should immediately provide supplemental oxygen therapy for patients with sari and respiratory distress, hypoxemia or shock. oxygen therapy flow rate should be aimed at spo2>=90%, spo2>=92-95% and spo2>=94%, in non-pregnant, pregnant and children, respectively. hcw should recognize severe hypoxemic respiratory failure when a patient with respiratory distress is failing standard oxygen therapy. high-flow nasal oxygen (hfno) or non-invasive ventilation (niv ) should be used in selected patients with hypoxemic respiratory failure. hypoxemic respiratory failure due to ards among these patients commonly results from intrapulmonary ventilation-perfusion mismatch or shunt and usually requires mechanical ventilation. thus, rapid sequence intubation should be performed using airborne precautions. implementation of mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted body weight) and higher positive end-expiratory pressure (peep) is suggested. patients with sari should be treated cautiously with intravenous fluids when there is no evidence of shock, because aggressive fluid resuscitation may worsen oxygenation. for resuscitation of septic shock in adults, at least 30 ml/kg of isotonic crystalloid should be infused in the first 3 hours of shock identification and in children rapid bolus of 20 ml/kg as loading dose and up to 40-60 ml/kg of isotonic crystalloid infusion in the first hour of shock identification is needed. vasopressor should be administered when shock persists during or after fluid resuscitation. if signs of poor perfusion persist despite reaching mean arterial pressure (map) target (i.e. >65 mmhg) with fluids and vasopressor, consider administering an inotrope such as dobutamine. empiric antimicrobials should be initiated within one hour of identification of sepsis to treat all likely pathogens causing sari. empiric antibiotic treatment should be based on the clinical diagnosis of severe pneumonia or sepsis, local epidemiology and susceptibility data as well as treatment guidelines. if influenza is also a concern and there is a local circulation of influenza virus, a neuraminidase inhibitor should be adjoined to empiric therapy. empiric antibiotic therapy should be de-escalated on the basis of microbiology results and clinical judgment. systemic corticosteroids should not be routinely adding to therapy unless indicated for another reason. collection of clinical specimens for laboratory diagnosis is suggested in early outbreak period and after that it is only advised for investigational purposes. if laboratory diagnosis is considered, serology is recommended only when rt-pcr is not available. otherwise, hcw should collect specimens from both the upper respiratory tract and lower respiratory tract for testing 2019-ncov via rt-pcr (5). at the time being, emergency preparedness and response for providing appropriate care to the patients suspected to coronavirus-associated acute respiratory illness (abovementioned plans) should be developed and implemented in the emergency departments, as the frontline of treating human infections of 2019-ncov in the hospitals. 1. appendix 1.1. conflict of interest none. 1.2. funding and support none. references 1. organization wh. novel coronavirus (2019-ncov ) situation report-9, 29 january 2020. geneva, switzerland. 2020. 2. organization wh. surveillance case definitions for human infection with novel coronavirus ( ncov ): interim guidance v1, january 2020. world health organization, 2020. 3. organization wh. novel coronavirus (2019-ncov ) advice for the public: interim guidance. world health organization. 4. organization wh. infection prevention and control during health care when novel coronavirus ( ncov ) infection is suspected: interim guidance, 25 january 2020. world health organization, 2020. 5. organization wh. clinical management of severe acute respiratory infection when novel coronavirus (2019ncov ) infection is suspected: interim guidance, 28 january 2020. world health organization, 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency. 2018; 6 (1): e14 le t t e r to ed i to r key performance indicators of chest pain management in emergency department; a letter to the editor mehrdad taghizadeh1, roghayeh taghipour1∗, kamran heydari1 1. emergency department, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2018; accepted: february 2018; published online: 18 february 2018 cite this article as: key performance indicators of chest pain management in emergency department; a letter to the editor. emergency. 2018; 6(1): e14. dear editor: chest pain is a common complaint among those presenting to emergency department (ed) and is associated with a high rate of mortality. based on national center for health statistics, chest pain leads to about 6 million visits to eds in united state. in iran, ischemic cardiac diseases are the second cause of death in people aged 15 to 49 years (1). while less than 10% of the patients presenting to ed with chest pain are affected with myocardial infarction (mi), 33% of mi cases are silent (2). timely diagnosis and revascularization of ischemic part, using thrombolytic agents or percutaneous coronary intervention (pci), can save cardiac function and the patient’s life (3). therefore, in this regard the emphasis is on rapid referral of the patients to treatment centers, initiation of diagnostic measures such as electrocardiography (ecg) and in case of meeting the required criteria, transfer to cat lab for pci. american heart association (aha) has introduced the proper door to ecg time as 10 minutes if it has not been done in the ambulance (4). based on this recommendation, aha has defined the aims of coronary reperfusion as prescription of thrombolytic in the initial 30 minutes after admission of the patient to ed or pci in the initial 90 minutes after admission to ed. efficacy of reperfusion therapy decreases with an increase in the time interval between manifestation of symptoms and initiation of treatment. potential delay in initiation of reperfusion therapy can be due to increase in door to data, data to decision, and decision to drug times. therefore, improvement of these times as a series of key performance indicators has always been of interest to health care managers. by performing a clinical audit on 781 patients with the ∗corresponding author: roghayeh taghipour; emergency department, loghman hakim hospital, makhsous street, lashgar junction, tehran, iran. tel: +989121370265 email: rota425@gmail.com mean age of 50.91 ± 16.76 (20 -93) years who were included via non-probability census sampling and had presented to ed of loghman hakim hospital, tehran, iran, during 1.5 years with the chief complaint of chest pain (53.3% male), the writers of the present letter estimated mean and standard deviation of door to first ecg performance time as 22.47 ± 16.59 (0 – 94) minutes. time interval between admission of the patient to receiving thrombolytic in this study was 46.60 ± 17.98 (22–82). mean and standard deviation of the time interval between ecg to making a decision for starting thrombolytic, for 23 patients with st segment elevation myocardial infarction (stemi), was 26.90 ± 18.15 (0 – 65) minutes. in addition decision time to injection of thrombolytic in this study was almost 0 since decision making was done in ed while the drug was present at the patient’s bedside. there was no significant difference between various working shifts including morning (22.62 ± 16.01 minutes), evening (22.15 ± 16.61 minutes), and night (22.24 ± 17.33 minutes) in this regard (p = 0.827). the final diagnosis was unstable angina for 151 (19.3%) cases, mi in 32 (4.1%) cases (23 stemi cases), and pulmonary embolism in 2 (0.3%) cases. as can be seen, door to first ecg time in the studied ed is approximately twice the standard time proposed by aha. in addition, door to drug time interval is also about 1.5 times more than the mentioned standard. managers of the mentioned ed attempted to relieve the problem by increasing the number of ecg devices and putting someone in charge of performing ecg for each shift. in addition, by training triage nurses it was decided that all the patients presenting to ed with complaint of non-traumatic chest pain, either typical or atypical, should undergo screening immediately using ecg in the fast track and their ecg should be interpreted by the senior resident in each shift. additionally, the method of recording the mentioned times was changed from manual, which was estimated and recorded with 3 to 5 minutes delay from the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. taghizadeh et al. 2 time of initiation of the measures by a nurse, to automatic with calibrated ecg devices. overall, it seems that improvement of the mentioned times needs constant care of the ed managers and continuous training of triage and ems personnel for acceleration of providing diagnostic and treatment services to these patients. it should be noted that fortunately by setting up “724 system” by the ministry of health and performance of ecg in the ambulance and transmitting the data from the ambulance to the dispatch center, this problem will be solved soon. 1. appendix 1.1. acknowledgements the personnel of loghman hakim hospital emergency department are thanked for their cooperation in performing the present research project. 1.2. author contribution all the authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 1.3. funding/support no financial support has been received. 1.4. conflict of interest there is none. references 1. forouzanfar mh, sepanlou sg, shahraz s, besc pn, pourmalek f, lozano r, et al. evaluating causes of death and morbidity in iran, global burden of diseases, injuries, and risk factors study 2010. archives of iranian medicine. 2014;17(5):304. 2. canto jg, shlipak mg, rogers wj, malmgren ja, frederick pd, lambrew ct, et al. prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. jama. 2000;283(24):3223-9. 3. roe mt, messenger jc, weintraub ws, cannon cp, fonarow gc, dai d, et al. treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. journal of the american college of cardiology. 2010;56(4):254-63. 4. o’gara pt, kushner fg, ascheim dd, casey de, chung mk, de lemos ja, et al. 2013 accf/aha guideline for the management of st-elevation myocardial infarction: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. journal of the american college of cardiology. 2013;61(4):e78-e140. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2019; 7 (1): e70 or i g i n a l re s e a rc h problem-based versus lecture-based method in prehospital trauma life support training; a pre-test post-test study masoumeh falaki1, rouzbeh rajaei ghafouri2∗, samad shams vahdati2 1. emergency medicine department, faculty of medicine, tabriz university of medical sciences, tabriz, iran. 2. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. received: august 2019; accepted: september 2019; published online: 24 november 2019 abstract: introduction: pre-hospital trauma life support (phtls) training is necessary for all emergency medical services (ems) personnel to increase their efficacy and skills. this study aimed to compare two methods of problembased learning (pbl) and lecture-based learning (lbl) for phtls training courses of ems personnel. methods: in this pre-post-test study, 144 male ems staff members were divided into two groups of pbl (n=72) and lbl (n=72). both groups received four sessions of phtls training based on 8th edition of phtls guideline. the participants’ knowledge and skills were evaluated before and three months after training and the two groups were compared in this regard. results: the mean knowledge score (63.59±13.43 to 81.08±4.66; p<0.001) and mean skills score (58.85±19.74 to 99.07±25.02; p<0.001) of participants had significantly improved after the training courses. both groups had similar scores before intervention, but pbl group had significantly higher scores in knowledge (p<0.001) and skills (p<0.001) after intervention. there was also a significantly higher change in knowledge (p<0.01) and skills (p<0.001) in pbl group compared to lbl group. conclusion: phtls training improves ems personnel’s knowledge and skill in managing trauma patients. pbl was more effective than lbl. keywords: multiple trauma; emergency medical services; problem-based learning; education cite this article as: falaki m, rajaei ghafouri r, shams vahdati s. problem-based versus lecture-based method in pre-hospital trauma life support training; a pre-test post-test study. arch acad emerg med. 2019; 7(1): e70. 1. introduction taking care of the critically injured begins well before the patient arrives at a large academic trauma center. pre-hospital care is the first part of the trauma treatment and care system (1). pre-hospital trauma life support (phtls) plays a very important role in the effective management of trauma patients and aims to provide high-quality care that reduces injury and mortality in these patients (2, 3). the success of the pre-hospital care depends on the knowledge and skill of emergency medical services (ems) personnel, which lead to improvements in the response time, interventions and, ultimately, the rapid transfer to the hospital (4-6). ems personnel are the first ones to examine and treat pre-hospital critical patients. it is important to increase the accuracy and speed ∗corresponding author: rouzbeh rajaei ghafouri; emergency medicine research team, tabriz university of medical sciences, daneshgah street, tabriz, iran. e-mail: rozbehrajaei@yahoo.com, rrajaei88@gmail.com, tel: +989143115624 of treatment to lower the mortality caused by these diseases (7). for this purpose, we need efficient and operational personnel to deal with various types of crashes and diseases (8, 9). it is important to increase the staff’s awareness regarding phtls to decrease the mortality rate and increase their confidence and knowledge (10). a recent study has reported that after phtls training, the mortality rate had decreased (11). there is a need to improve ems staff’s knowledge and attitude regarding phtls. primary trauma care courses can provide the basic knowledge and skills necessary for identification and treatment of trauma patients in need of immediate resuscitation and stabilization of the injuries. these courses can teach an acceptable method for treating patients affected by trauma (5, 12). there are two common methods used for training, lecture-based learning (lbl) and problem solving methods (13). problem-based learning (pbl) was implemented in the 1960s, which is now found in many training settings including medical sciences. pbl is an educational method focused on self-directed learning and small group this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. falaki et al. 2 discussions, which can provide learners with more opportunities for application of knowledge compared to traditional lbl method. nowadays experts believe that pbl has many advantages over lbl, including flexible knowledge, promotion of communications and collaborative skills, and selfdirected learning skills in a motivating format (14). trauma care learning needs both knowledge and skill improvement, so lbl alone may not enhance trauma management skills. in this study, we compared the two methods of lbl and problem based method in improving knowledge and skills of ems personnel regarding phtls. 2. methods 2.1. study design and setting in this preand post-test study, 144 ems staff members of east azerbaijan province who were participating in phtls courses during 2017 were divided into two groups of lbl and pbl. both groups received four sessions of phtls training based on 8th edition of phtls guideline. the participants’ knowledge and skills were evaluated before and three months after training and the two groups were compared in this regard. informed consent was obtained before administering the questionnaire. the ethics committee of tabriz university of medical sciences approved the study (ethic no. ir.tbzmed.rec.1396.421). the score of each participant was kept secret and only the organizer of courses knew it. 2.2. participants all of the paramedics working in tabriz ems (154 persons) were included as study population. during courses, 10 participants were excluded from the study due to not completing the sessions or filling the post-test. participants were divided into two equal groups of 72 cases. first group had the course in lbl method and the second group in pbl method. 2.3. data gathering demographic variables (age, employment duration, level of education) were collected using a pre-designed check list and knowledge and skill were measured and registered before and after implementation of the training course using reliable and valid questionnaires, by an emergency medicine resident. 2.4. intervention knowledge of participants who attended four sessions in august, september, october and november 2017 was measured before (pre-test) as well as three months after the sessions (post-test). their knowledge was measured using phtls 8th edition questionnaire (15). participants’ skills on managing trauma patients in the pre-hospital situations were also measured before and three months after phtls sessions using a checklist containing criteria of basic and advanced life support, time to response and time to reach the hospital (appendix 1). the checklist was prepared according to expert opinion and based on phtls concept and its validity (0.72) and reliability (0.90) were defined using test-re-test method. the skills of paramedics were evaluated when treating trauma patients who presented to emergency department of imam reza, referral trauma center, tabriz. for each ems staff member, only one multiple trauma patient was selected. in this exam, outcome of the course was pass or fail. paramedics who failed the exam had to repeat the course in the same manner until they could pass successfully. after 3 months, participants were evaluated in the triage area while they transferred a multiple trauma patient to emergency department. an emergency medicine resident did the evaluation and filled the checklist of evaluation without the ems personnel sensing. there was not any interference in the standard course of patient treatment. the resident responsible for data gathering was not aware of the type of learning method as well as final scores of participants. the phtls courses were held in tabriz ems center. we had no loss to follow up because all of the trained paramedics had to refer trauma patients of all around tabriz to the sole referral hospital of the region. for preventing bias, the two groups were trained by one faculty member and outcomes (knowledge and skills) were measured by a trained emergency medicine resident. 2.5. statistical analysis all data were analyzed using spss software (version 23; spss inc., chicago, il). the results are expressed as mean ± standard deviation or percentage. kolmogorov-smirnov test was used to assess normal distribution of data. chi square test, independent t-test or mann-whitney u test were used to compare data between the groups. paired-samples t-test or wilcoxon rank test were used to compare preand post-test results. p-values less than 0.05 were considered statistically significant. 3. results in this study 144 male ems staff members were evaluated in two learning groups. the two groups were similar regarding the baseline characteristics (table 1). the mean knowledge score (63.59±13.43 vs 81.08±4.66; p<0.001) and mean skill score (58.85±19.74 vs 99.07±25.02; p<0.001) of participants had significantly improved after applying the training methods. participants’ scores on knowledge and skills before and after training and their changes are shown in table 2. both groups had similar knowledge and skills score before intervention, but pbl group had significantly higher scores in both items after intervention. there was also a signifithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e70 table 1: comparing the baseline characteristics of participants between the two learning method groups variable problem based lecture based p-value age (year) mean ± sd 34.96±8.40 36.60±8.16 0.18 employment duration (years) mean±sd 7.61±5.63 8.67±6.66 0.24 educational degree bachelor 37 (38.9) 42 (47.7) 0.23 associate degree 58 (61.1) 46 (52.3) data are presented as mean ± standard deviation (sd) or frequency (%). table 2: comparing the knowledge and skills of emergency medicine services (ems) personnel before and after training with problem based and lecture based learning methods variables problem based lecture based p value knowledge before 62.56±12.93 64.69±13.93 0.29 after 82.58±4.96 79.48±3.71 <0.001 change 38.27±32.69 29.77±36.88 0.01 skills before 57.80±18.88 60.00±20.67 0.45 after 116.91±12.85 79.81±20.20 <0.001 change 121.69±65.03 39.09±21.37 <0.001 data are presented as mean ± standard deviation. cantly higher change in knowledge and skills in pbl group compared to lbl group. 4. discussion our study showed that phtls training improves ems personnel knowledge and skill in managing trauma patients and pbl method was more effective than lbl. pre-hospital care is a critical phase to improve trauma patients’ outcomes during episodic care. ems and first-responder personnel must be capable of providing life-saving interventions at scene with proper, quick and correct treatment decisions; so, there is a need to train these personnel to have high confidence and skills in initiating procedures under adverse circumstances (16). for this purpose, phtls courses have been introduced and used for training paramedics and technicians. their aim is to increase the skills of ems personnel in managing trauma patients by improving their knowledge of trauma care and make them able to act faster in life-threatening situations. cognitive knowledge, technical skills and clinical judgment are the main pillars for healthcare providers (17). in this study, we evaluated the knowledge and skills of ems personnel before and after phtls courses and observed that overall, there was a significant improvement in participants’ knowledge of the situation, management, and their skills when encountering trauma patients after training. frank and colleagues (10) reported that phtls leads to significant increase in confidence and knowledge. haske et al. (2) reported that the participants’ skills and knowledge on pre-hospital care of trauma patients would increase in short term, but the knowledge and safety would not remain the same on some issues in long term. a systematic review demonstrated improved management of trauma patients and shortened time to definitive care following phtls training (18). improved individual management of trauma patients was also reported following primary trauma care courses (19). van dillen and colleagues (16) observed that simulation training improved prehospital care providers’ confidence level in performing two life-saving procedures. therefore, any type of training would help improve ems personnel’s confidence and skill, and as previous studies in the same area with our study have suggested, ems personnel require more education and supervision to provide services according to phtls guidelines (20). previous studies indicated that the effects of training would decrease after a period (2, 18). although we did not evaluate the participants in long term, but it is obvious that continuing training programs are necessary for an effective and sufficient ems, and personnel should attend phtls courses at least once a year. besides these findings, we evaluated the effects of problem based and lbl methods of training on achieving better knowledge and skills and observed that problem based method led to a significantly greater improvement in participants’ knowledge and most importantly this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. falaki et al. 4 appendix 1: checklist for evaluating the participants’ skills on managing trauma patients in the pre-hospital setting action weight done not doneˆ appropriate$ inappropriate# 1. cervical spine immobilization 10* – – – 2. airway management if needed 10* – – – 3. oxygen administration 8* – – – 4. peripheral iv line establishment 8* – – – 5. external bleeding control 8* – – – 6. spinal immobilization 8* – – – 7. serum administration 7* – – – 8. immobilization of limb fracture 6* – – – 9. vital signs 4* – – – $: two points; #: one point; ∧: zero point their skills in managing trauma patients. pbl enables students to identify the gaps in their knowledge and enhance their group functioning and generic skills (21). most participants in medical courses prefer practical trainings to theoretical knowledge. faisal and colleagues (13) have also indicated that pbl is more effective than lbl in the academic performance of medical students. 5. limitation this study was confined by some limitations; being singlecentered and having a small sample size were among the main limitations of the study. we did not follow the participants to evaluate the long term efficacy of phtls training. in addition, the effect of phtls training on reducing time to respond and mortality rate were not evaluated. although we did not evaluate the long-term efficacy of phtls training, continuing training programs are necessary for an effective and sufficient ems. in further evaluations, the proper time to re-educate the personnel should also be evaluated. we recommend evaluating the personnel in long-term periods, like two and five years, for better results. paramedics who are working in rural pre-hospital centers were not included in this study. it was not possible to gather all of the paramedics working in east azerbaijan province to participate in courses at the same time. another limitation is that we could not follow up the maintenance of efficacy of education for more than three months. it would be better if the knowledge and skills of participants were measured 6-12 month later to evaluate the behavior change in management of trauma patients. 6. conclusion phtls training improves ems personnel’s knowledge and skill in managing trauma patients. pbl was the more effective method of training compared to traditional lbl. 7. appendix 7.1. acknowledgements we would like to thank tabriz disaster and pre-hospital management center. authors also declare their special thanks to personnel of emergency department of imam reza hospital, tabriz, iran. 7.2. author contribution this study is derived from dr. masoumeh falaki’s postgraduate thesis to join the iranian board of emergency medicine, who was responsible for data gathering 3 months after the courses. dr. samad shams vahdati analyzed the data and contributed in manuscript writing. dr. rouzbeh rajaei ghafouri, the corresponding author, is responsible for study design, pre-test/ post-test evaluation, and organizing the training courses. authors orcids masoumeh falaki: 0000-0001-7646-6235 rouzbeh rajaei ghafouri: 0000-0002-3760-572x samad shams vahdati: 0000-0002-4831-6691 7.3. funding/support none. 7.4. conflict of interest none. references 1. fedor pj, burns b, lauria m, richmond c. major trauma outside a trauma center: prehospital, emergency department, and retrieval considerations. emergency medicine clinics. 2018;36(1):203-18. 2. haske d, beckers sk, hofmann m, lefering r, grutzner pa, stockle u, et al. subjective safety and self-confidence in prehospital trauma care and learning progress afthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e70 ter trauma-courses: part of the prospective longitudinal mixed-methods epptc-trial. scandinavian journal of trauma, resuscitation and emergency medicine. 2017;25(1):79. 3. murad mk, larsen s, husum h. prehospital trauma care reduces mortality. ten-year results from a time-cohort and trauma audit study in iraq. scandinavian journal of trauma, resuscitation and emergency medicine. 2012;20(1):13. 4. mlcak rp, buffalo mc, jimenez cj. prehospital management, transportation, and emergency care. total burn care: elsevier; 2018. p. 58-65. e1. 5. henry ja, reingold al. prehospital trauma systems reduce mortality in developing countries: a systematic review and meta-analysis. j trauma acute care surg. 2012;73(1):261-8. 6. beuran m, paun s, gaspar b, vartic m, hostiuc s, chiotoroiu a, et al. prehospital trauma care: a clinical review. chirurgia. 2012;107:564-70. 7. bidari a, abbasi s, farsi d, saeidi h, mofidi m, radmehr m, et al. quality assessment of prehospital care service in patients transported to hazrat-e-rasoul akram hospital. 2007. 8. heidari m, shahbazi s. effect of training problem-solving skill on decision-making and critical thinking of personnel at medical emergencies. international journal of critical illness and injury science. 2016;6(4):182. 9. ghaniyoun a, heidari m, shakeri k. psychological empowerment and its associated factors among operational staff of tehran emergency center. j clin diagn res. 2018;12(6). 10. frank cb, wãűlfl cg, hogan a, suda aj, guhring t, gliwitzky b, et al. phtlsâő(prehospital trauma life support) provider courses in germanyâăşwho takes part and what do participants think about prehospital trauma care training? journal of trauma management & outcomes. 2014;8(1):7. 11. johansson j, blomberg h, svennblad b, wernroth l, melhus h, byberg l, et al. prehospital trauma life support (phtls) training of ambulance caregivers and impact on survival of trauma victims. resuscitation. 2012;83(10):1259-64. 12. amiri h, gholipour c, mokhtarpour m, vahdati ss, aghdam yh, bakhshayeshi m. two-day primary trauma care workshop: early and late evaluation of knowledge and practice. eur j emerg med. 2013;20(2):130-2. 13. faisal r, khalil-ur-rehman bs, shinwari l. problembased learning in comparison with lecture-based learning among medical students. jpma the journal of the pakistan medical association. 2016;66(6):650-3. 14. ding x, zhao l, chu h, tong n, ni c, hu z, et al. assessing the effectiveness of problem-based learning of preventive medicine education in china. scientific reports. 2014;4:5126. 15. technicians naoem. phtls: prehospital trauma life support. 8 th ed: jones & bartlett learning; 2014. 725 p. 16. van dillen cm, tice mr, patel ad, meurer da, tyndall ja, elie mc, et al. trauma simulation training increases confidence levels in prehospital personnel performing life-saving interventions in trauma patients. emergency medicine international. 2016;2016. 17. shemin rj. postgraduate experiential learning is essential for surgical maturation. the journal of thoracic and cardiovascular surgery. 2015;150(5):1069-70. 18. jayaraman s, sethi d. advanced trauma life support training for ambulance crews. cochrane database of systematic reviews. 2010(1). 19. ologunde r, le g, turner j, pandit h, peter n, maurer d, et al. do trauma courses change practice? a qualitative review of 20 courses in east, central and southern africa. injury. 2017;48(9):2010-6. 20. gholipour c, vahdati ss, notash m, miri sh, ghafouri rr. success rate of pre-hospital emergency medical service personnel in implementing pre hospital trauma life support guidelines on traffic accident victims. turkish journal of emergency medicine. 2014;14(2):71-4. 21. ibrahim me, al-shahrani am, abdalla me, abubaker im, mohamed me. the effectiveness of problem-based learning in acquisition of knowledge, soft skills during basic and preclinical sciences: medical students’ points of view. acta informatica medica. 2018;26(2):119. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 121 emergency (2014); 2 (3): 121-124 original research diagnostic accuracy of ultrasound in detection of traumatic lens dislocation seyed hossein ojaghi haghighi1, hamid reza morteza begi1, raana sorkhabi2, mohammad kazem tarzamani3, golshan kamali zonouz1*, akram mikaeilpour4, farzad rahmani1 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. department of ophthalmology, tabriz university of medical sciences, tabriz, iran 3. department of radiology, tabriz university of medical sciences, tabriz, iran 4. department of cardiology, tabriz university of medical sciences, tabriz, iran abstract introduction: traumatic eye injuries (tei) involved about 3% of cases referred to the emergency departments of developing countries. lens dislocation is one of the critical cases of ophthalmic emergencies. the present study was aimed to evaluate the diagnostic accuracy of ultrasonography in detection of traumatic lens dislocation. methods: in this cross-sectional study the findings of ultrasonography and orbital computed tomography (oct) of head and face trauma patients, referred to imam reza hospital, tabriz, iran, from july 2013 to june 2014, have been compared. the sensitivity, specificity, positive and negative likelihood ratio, positive and negative predictive value, and accuracy of ultrasonography were calculated. cohen's kappa coefficient was presented to assess the agreement of ultrasonography with oct findings. results: one hundred thirty patients with the mean age of 35.4±18.0 were evaluated (75.4% male). sensitivity and specificity of ultrasonography were 84.6% (95% cl: 53.797.3) and 98.3% (95% cl: 93.399.7), respectively. in addition, positive and negative likelihood ratio were calculated 49.5 (95% cl: 12.3-199.4) and 0.15 (95% cl: 0.040.56), respectively. cohen's kappa coefficient of 0.83 (95% cl: 0.66-1.0; p<0.0001) was representative of excellent agreement of these two tests. conclusion: the finding of this project was representative of 84.6% sensitivity, 98.3% specificity, and 96.9% accuracy of ultrasonography in detection of traumatic lens dislocation. it seems that in cases, which oct is not possible, ultrasonography, could be an acceptable option to assess traumatic eye injuries. key words: ultrasonography; diagnostic techniques; ophthalmological; lens subluxation; eye injuries, trauma cite this article as: ojaghi haghighi sh, morteza begi hr, sorkhabi r, et al. diagnostic accuracy of ultrasonography in detection of traumatic lens dislocation. emergency. 2014;2(3):121-4. introduction:1 raumatic eye injuries (tei) involved about 3% of cases visited in emergency departments (ed) of developing countries (1). it is estimated that trauma causes blindness and visual impairment in many referees of ophthalmic emergency (2). most of these injuries are hard to diagnose in initial ed assessment. on the other hand, more frequent examinations to detect injuries maybe hazardous for the patient (3). orbital computed tomography (oct) scan, magnetic resonance imaging (mri), ultrasonography, and slitlamp are introduced as the most important imaging tools to evaluate tei (4-8). although mri presents high accurate and quality images, it is an expensive and time-consuming test, which is not accessible in all *corresponding author: kamali zonouz golshan; emergency medicine department, imam reza hospital, tabriz university of medical sciences, golgasht avenue, tabriz, iran, tel/fax: 00984113352078 e-mail: g.kamali.z@gmail.com received: may 2014; accepted: june 2014 emergency centers. optical methods are cost effective and easy to use, but they have a low accuracy in evaluation of injuries to optical structures such as sclera, pupil, and cornea, as well as hemorrhage. while ultrasonography, known as a non-expensive, accessible, and safe method, has a high accuracy in evaluation of injuries to optical structures (3). when the patient is noncooperative for fundoscopic tests or suffers from severe edema, chemosis, or hyphema, eye ultrasonography can present valuable and useful information to the physician (9). but, it should be mentioned that diagnostic accuracy of ultrasonography is highly dependent to operator proficiency and it is not reliable in detecting parenchymal injuries (10). lens dislocation is one of the critical cases of ophthalmic emergencies referred to partial or complete dislocation of eye lens from its natural location to posterior chamber. trauma is one of the most common reasons of lens dislocation (11). the fast diagnosis of such an injury can be greatly help improvt mailto:g.kamali.z@gmail.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com ojaghi haghighi et al 122 ing the patients' outcomes. diagnostic accuracy of ultrasonography in assessment of traumatic lens dislocation is evaluated in a few studies. whereas some of investigations suggested oct as an accurate method (12), others consider ultrasonography as a valuable diagnostic tool in detection of lens dislocation, especially in lack of oct (13-16). however, the low number of studied samples in this field is the critical limitation. therefore, the present study was performed to evaluate the diagnostic value of ultrasonography versus oct in traumatic lens dislocation. methods: study design and setting: in this cross-sectional study the findings of ultrasonography and oct of multiple trauma patient with head trauma, referred to imam reza hospital, tabriz, iran, from july 2013 to june 2014, have been compared. data collection and ultrasonography was done by an emergency medicine specialist. octs (as a gold standard tool) were interpreted by a radiologist who was blind to the aim of study. the protocol of the present project was studied and confirmed by the ethical committee of tabriz university of medical sciences. all researchers adhered the helsinki declaration during the study. the study protocol did not have any interference with treatment process and no danger threatened patients. the collected forms were anonymous and for each patient an especial code registered. before the study, patients filled the personal consent form. participants in this study, multiple trauma patients with tei were entered. patients with irregularity of the globe contour, and lack of ability to cooperate for imaging were excluded from the study. sample selection was sequentially. for determining of the sample volume, the least needed samples were achieved 121 persons noticing to at least 93% sensitivity of ultrasonography to detect tei, 15% prevalence (12), 95% confidence interval (α=0.05), 90% power (β= 0.1), and maximum error of 1% (d= 0.01). measurements the emergency medicine specialist was prospectively assessed demographic data (age, sex, and trauma mechanism), clinical symptoms of each patient, and registered them in data gathering form. then, the patients underwent eye ultrasonography by a trained emergency medicine specialist. ultrasonography was done using bedside machine (gh healthcare; logiq 200, pro series; korea) with 10 mhz micro-convex linear transducer in sagittal and transverse plane and closed eye technique with water-soluble gel. then patients referred to ed radiology unit for performing oct. the findings of oct was interpreted by a radiologist blind to the goal of study and recorded. oct was done using a toshiba asteion 16 slices scanner with considering the one-millimeter distance between image slices. both ultrasonography and oct was performed in recumbent position. statistical analysis data were entered to spss version 21.0 and imaging findings reported as the frequency and percentage. for evaluating the quality of ultrasonography receiver operating characteristic (roc) curve was drown and finally sensitivity, specificity, accuracy, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value calculated. cohen's kappa coefficient was presented to assess the agreement of ultrasonography with oct findings. p<0.05 was considered as a significant level. results: 130 patients with the mean age of 35.4±18.0 were entered to the study (75.4% male). five patients (3.8%) had systolic blood pressure below 90 and 32 ones table 1: clinical and demographic characteristics of studied patients  clinical characteristic frequency (%) gender male 32 (24.6) female 98 (75.4) hypotension no 125 (96.2) yes 5 (3.8) glasgow coma scale 14-15 74 (56.9) 9-13 35 (26.9) 3-9 21 (16.2) mechanism pedestrian 20 (15.4) car (driver) 51 (39.2) motorcycle (driver) 36 (27.7) falling 8 (6.15) intentional injuries 7 (5.4) other 8 (6.15) visual accuracy normal 57 (43.85) abnormal 8 (6.15) no cooperation 65 (50.0) laceration no 73 (56.15) yes 57 (43.85) ecchymosis no 17 (13.1) yes 113 (89.9) eye bleeding no 128 (98.5) yes 2(1.5) globe rupture no 124 (95.4) yes 6 (4.6) periorbital edema no 67 (51.5) yes 63 (48.5) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 123 emergency (2014); 2 (3): 121-124 (24.6%) suffered from tachycardia. gcs of 21 patients (16.15%) was below nine and in 35 ones (26.9%) within 9-13 (table 1). the most common mechanism of accident in the patients was related to car (39.2%), motorcycle (27.7%), and pedestrian accidents (15.4%), respectively. oct evaluation has detected 13 cases (10%) of traumatic lens dislocation. the findings of ultrasonography in 11 cases were compatible with oct with two false negative cases, while two false positive were found by ultrasonography. the area under the roc curve of ultrasonography in traumatic lens dislocation was achieved 0.9145 (95% cl: 0.81-1.0) (figure 1). sensitivity and specificity of ultrasonography were 84.6% (95% cl: 53.7-97.3) and 98.3% (95% cl: 93.399.7), respectively. positive and negative likelihood ratio of this diagnostic test in detection of lens dislocation were calculated 49.5 (95% cl: 12.3-199.4) and 0.15 (95% cl: 0.04 0.56), respectively (table 2). cohen's kappa coefficient of 0.83 (95% cl: 0.66-1.0; p<0.0001) was representative of excellent agreement of these two tests. discussion: the findings of the present study showed 84.6% sensitivity and 98.3% specificity of eye ultrasonography in detection of traumatic lens dislocation. the accuracy of this diagnostic test was 96.9%. based on these results, it seems that in cases, which oct is not possible, ultrasonography, could be an acceptable alternative for evaluation of lens dislocation. there are a few study assessed the diagnostic value of ultrasonography in detection of lens dislocation. imran et al. revealed that sensitivity and specificity of ultrasonography are 75% and 97.9% in diagnosis of lens dislocation, respectively (12). blavis and colleagues by study of 61 patients observed two cases of lens dislocation both of which was detected by ultrasonography (13). the trivial difference between previous studies and the present project could be due to operator-dependent of ultrasonography. on the other hand, reaching a certain diagnosis is time consuming and ophthalmic consultants are not present in all hospitals. all of these issues maybe lead to delay in detection and management whereas eye ultrasonography can be helpful in such situations. however, eye ultrasonography has not yet common in ophthalmic clinicians. in addition, eye ultrasound transducers for eye ultrasonography are different from common transducers applied in the ed (13). in addition, it should be mentioned that clinical evaluation of patients with tei is painful and not possible in many cases. although there is no information regarding the negative effect of entered energy by high frequency ultrasonography on eye structures, more investigation is required in this area. one of the limited studies in this field revealed that using ultrasonography with frequency of 10 to 60 mhz did not have any destructive effects on visual field and histological findings. but, the recent study showed that using ultrasonography causes to increase the internal temperature of eye (17). however, researchers expressed that this test should be used preciously until finding appropriate solutions to the above problems. conclusion: the finding of this project was representative of 84.6% sensitivity, 98.3% specificity, and 96.9% accuracy of ultrasonography in detection of traumatic lens dislocation. it seems that in cases, which oct is not possible, ultrasonography, could be an acceptable option to assess traumatic eye injuries. acknowledgments: authors would like to say thanks to all patients and stuffs of the emergency department of imam reza hospital for their contribution. this article has been written in terms of the residency thesis registered in tabriz university of medical sciences. conflict of interest: none table 2: diagnostic accuracy of ultrasonography in detection of traumatic lens dislocation  value rate (95% ci) sensitivity 84.6 (53.7-97.3) specificity 98.3 (93.3-99.7) positive predictive value 84.6 (53.7-97.3) negative predictive value 98.3 (93.3-99.7) positive likelihood ratio 49.5 (12.3-199.4) negative likelihood ratio 0.15 (0.04-0.56) accuracy 96.9 (93.9-99-9) ci: confidence interval. 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 s e n si ti v it y 0.00 0.25 0.50 0.75 1.00 1 specificity area under roc curve = 0.9145 figure 1: the receiver operating characteristic (roc) curve of ultrasonography in detection of traumatic lens dislocation.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com ojaghi haghighi et al 124 funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. kubal ws. imaging of orbital trauma. radiographics. 2008;28(6):1729-39. 2. mcclenaghan f, ezra d, holmes s. mechanisms and management of vision loss following orbital and facial trauma. curr opin ophthalmol. 2011;22(5):426-31. 3. silverman rh. high‐resolution ultrasound imaging of the eye–a review. clin experiment ophthalmol. 2009;37(1):54-67. 4. brisco j, fuller k, lee n, andrew d. cone beam computed tomography for imaging orbital trauma—image quality and radiation dose compared with conventional multislice computed tomography. br j oral maxillofac surg. 2014;52(1):76-80. 5. nowinski wl. the future of imaging in orbital disease. new york: marcel dekker; 2004. p. 353-70. 6. nayak b, desai s, maheshwari s. interpretation of magnetic resonance imaging of orbit: simplified for ophthalmologists (part i). j clin ophthalmol res. 2013;1(1):29-35. 7. amini a, eghtesadi r, feizi am, et al. sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. emergency. 2013;1(1):15-9. 8. frasure se, saul t, lewiss re. bedside ultrasound diagnosis of vitreous hemorrhage and traumatic lens dislocation. am j emerg med. 2013;31(6):1002. e1-2. 9. zvornicanin j, jusufovic v, cabric e, musanovic z, zvornicanin e, popovic-beganovic a. significance of ultrasonography in evaluation of vitreo-retinal pathologies. med arh. 2012;66(5):318-20. 10. poletti pa, kinkel k, vermeulen b, irmay f, unger pf, terrier f. blunt abdominal trauma: should us be used to detect both free fluid and organ injuries? . radiology. 2003;227(1):95-103. 11. wang r, bi c-c, lei c-l, sun w-t, wang s-s, dong x-j. multiple methods of surgical treatment combined with primary iol implantation on traumatic lens subluxation/dislocation in patients with secondary glaucoma. int j ophthalmol. 2014;7(2):264-72. 12. imran s, amin s, daula mih. imaging in ocular trauma optimizing the use of ultrasound and computerised tomography. pak j ophthalmol. 2011;27(3):146-51. 13. blaivas m, theodoro d, sierzenski pr. a study of bedside ocular ultrasonography in the emergency department. acad emerg med. 2002;9(8):791-9. 14. eken c, yuruktumen a, yildiz g. ultrasound diagnosis of traumatic lens dislocation. j emerg med. 2013;44(1):e109-10. 15. eze kc, enock me, eluehike su. ultrasonic evaluation of orbito-ocular trauma in benin-city, nigeria. niger postgrad med j. 2009;16(3):198-202. 16. silverman rh, lizzi fl, ursea bg, et al. safety levels for exposure of cornea and lens to very high-frequency ultrasound. j ultrasound med. 2001;20(9):979-86. 17. palte hd, gayer s, arrieta e, et al. are ultrasound-guided ophthalmic blocks injurious to the eye? a comparative rabbit model study of two ultrasound devices evaluating intraorbital thermal and structural changes. anesth analg. 2012;115(1):194-201. archives of academic emergency medicine. 2019; 7 (1): e63 or i g i n a l re s e a rc h characteristics of traumatic urogenital injuries in emergency department; a 10-year cross-sectional study babak javanmard1, morteza fallah-karkan1,2, mohammadreza razzaghi2∗, anahita ansari djafari1, saleh ghiasy1, behzad lotfi1, reza vafaee3 1. urology department, shohada e tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. laser application in medical science research center, shahid beheshti university of medical sciences, tehran, iran. 3. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. received: july 2019; accepted: september 2019; published online: 9 november 2019 abstract: introduction: urogenital system injuries (ugis) are seen in 10% of adult cases with multiple trauma. although ugis are rarely life threatening, they can cause major long-term morbidities. this study aimed to evaluate the characteristics of traumatic ugis in patients who were referred to emergency department following multiple traumas. methods: this retrospective cross-sectional study was conducted on multiple trauma patients who were presented to emergency department during a 10-year period (2008-2017). all patients with kidney, ureter, bladder, urethra, or external genitalia injuries were studied. the patients’ data were extracted from their clinical profiles. results: out of the 13598 admitted patients in our trauma center, ugis were seen in 267 (1.9%) cases. the mean age of patients with ugis was 27.3 ± 6.1 years (74.15% male). the highest incidence of ugi was seen in those aged between 21 and 30 years (39.7%) and motorcycle accidents (49%) was the most frequent cause of trauma. 221 patients had an unstable situation and were emergently transferred to operation room (13.57% with traumatic kidney injury). the most common injured sites of urogenital system were kidney with 155 (58%) cases, followed by external genitalia with 91 (34.1%) cases. 77.5% of cases were managed conservatively and the rest (22.5%) underwent surgical procedures. conclusion: ugis comprise a low percentage (2%) of traumatic injuries, which are mostly caused by blunt trauma due to road traffic accidents. kidney is the most common injured organ and ugis mostly happen in young ages. keywords: urogenital system; acute kidney injury; wounds and injuries; multiple trauma; epidemiology; mortality cite this article as: javanmard b, fallah-karkan m, razzaghi m, ansari djafari a, ghiasy s, lotfi b, vafaee r. characteristics of traumatic urogenital injuries in emergency department; a 10-year cross-sectional study. arch acad emerg med. 2019; 7(1): e63. 1. introduction with economic development, incidence of traffic and industry-related accidents, iatrogenic injury, intoxication and also psychological self-mutilation have been increasing (1-8). morbidity due to trauma has been one of the most serious public health concerns all over the world (9). in most reports, urogenital system injuries (ugis) are seen in approximately 10% of adult traumatic patients and in less than 3% of children with multiple/severe trauma of lower abdomen or pelvis (10-12). kidney is the most common injured organ in ∗corresponding author: mohammadreza razzaghi; laser application in medical science research center, shahid beheshti university of medical sciences, tehran, iran. tel: +98 9121482592, fax: +98 2122712234, email: mrazaghi@sbmu.ac.ir. genitourinary system while ureteral traumas are rare (1, 13). although ugis are rarely life threatening, they can cause significant long-term morbidities such as renal function impairment, sexual dysfunction and urethral stricture (14-16). finding an ideal management in patients with ugis requires comprehensive epidemiological information in different populations and times (14, 17). therefore, this study aimed to evaluate the characteristics of traumatic ugis in patients who were referred to emergency department following multiple traumas. 2. methods 2.1. study design and setting this retrospective cross-sectional study was conducted on multiple trauma patients who were presented to emergency department of shohada-e-tajrish hospital, tehran, iran, durthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. javanmard et al. 2 ing a 10-year period (2008-2017). this hospital is the main referral trauma center in north and northeast of tehran. the ethics committee of shohada-e-tajrish hospital approved this study and gave us permission to review patients’ medical data. considering the retrospective design of the study, the ethical committee ceded the necessity to have patients provide consent for collecting their medical data. the patients’ data were collected confidentially and de-identified. 2.2. participants all admitted patients for more than 6 hours with any kind of traumatic ugis such as kidney, ureter, bladder, urethra, external genitalia and adrenal gland injuries, were included using a census sampling method. patients with incomplete medical profiles or unclear evidence regarding the urogenital tract were excluded. there was not any age or gender limitation. 2.3. data gathering we reviewed all information regarding demographic characteristics (age, gender), history, physical examination, mechanism of injury, type and severity of ugis, associated injuries, done procedures, and also type of management (conservative or surgical managements) by referring to the medical records of the cases and filling out a checklist designed for the investigation. the type and mechanism of the injury were adapted according to the international classification of diseases, 10th revision (icd-10)(18). two senior urology residents (mfk and sg) were responsible for data gathering. 2.4. statistical analysis statistical analyses were performed by the statistical package of social science system software, version 20. findings were presented using descriptive statistics as mean ± standard deviation or frequency (%). 3. results 3.1. baseline characteristics of studied patients out of 13598 admitted patients in our trauma center during the study period, ugis were seen in 267 (1.9%) patients (92.5% blunt and 7.5% penetrating trauma). table 1 shows the baseline characteristics of studied patients. the mean age of patients with ugis was 27.3 ± 6.1 (3 82) years (74.15% male). the highest incidence of ugi was seen in those aged between 21 and 30 years (39.7%) followed by 11-20 years (25.07%) and 3 -10 years (19.1%) age groups. motorcycle accidents (49%) followed by falling down (26%) were the most frequent causes of trauma. 221 patients had unstable situation and were emergently transferred to operation room (13.57% with traumatic kidney injury). 7 (2.8%) cases died due to severity of associated injuries (5 patients had renal table 1: baseline characteristics of studied patients variables number (%) gender male 198 (74.15) female 69 (25.8) age (year) 3 – 10 51 (19.1) 11 –20 67 (25.07) 21 –30 106 (39.7) 30 – 60 31 (11.4) >60 12 (4.73) trauma mechanism motorcycle accident 131(49) falling down 69 (26) car accident 58 (21.6) sports accident 9 (3.3) hemodynamics stable 238 (89.2) unstable 29 (10.8) associated injuries abdominopelvic 104 (38.8 ) extremities 85 (31.9) thoracic 46 (17.1) head and neck 32(12.2) presenting sign and symptom hematuria 169 (63.2) flank pain 50 (19.1) flank or genital abrasion 19 (7.1) obstruction 15 (5.6) other 14 (5.2) and 2 cases had bladder injuries). the most common injured sites of urogenital system were kidney with 155 (58%) cases, followed by external genitalia with 91 (34.1%) cases (table 2). the common associated injuries were extremity (52.8%) and abdominopelvic (41.9%) injuries. 3.2. management strategies table 3 summarizes different types of treatment strategies used for management of injured patients. upper urinary tract conservative management was applied for 51.8% of patients with renal injury and 2 patients with grade iv renal injury underwent angiographic embolization. two patients with adrenal trauma were managed conservatively. lower urinary tract nineteen cases out of 27 patients with extra peritoneal bladder rupture were managed conservatively, by foley catheter insertion for two weeks. in one case with extra peritoneal bladder rupture, during orthopedic surgery bladder was injured intra peritoneally so cystoraphy was done intraoperatively. fourteen of 25 patients with testis trauma had intact tunica albuginea and underwent conservative management. three patients needed dermal flap to reform scrota because this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e63 table 2: distribution of urogenital injuries among the studied subjects injured organ number (%) upper urinary tract renal 155 (58.1) ureter 3 (1.1) adrenal 2 (0.7) lower urinary tract scrotum 43 (16.1) testis 25(9.3) urethra 15(5.6) bladder 34 (12.7) genitalia 25 (9.9) severity of renal injury grade 1 103 (38.5) grade 2 34 (12.7) grade 3 10 (3.7) grade 4 5 (1.8) grade 5 3 (1.1) type of bladder injury intra peritoneal injury 7 (2.6) extra peritoneal injury 27 (10.1) type of ureteral injuries partial rupture of urethra 10(3.7) complete rupture of urethra 5(1.8) table 3: management strategies of studied patients variables number (%) type of management conservative management 207(77.5) operative management 52(19.4) type of procedures nephrectomy 7(2.6) bladder repair 8(2.9) immediate endoscopic realignment 10(3.7) renoraphy 10(3.7) ureter repair 2(0.7) partial orchiectomy 5(1.8) male genital organ repair 8(2.9) female genital organ repair 2(0.7) of extensive external genitalia injuries. nine men and one girl with external genitalia injuries were managed conservatively. ten of fifteen patients with urethral injuries underwent primary realignment (seven cases had complete urethral injuries). for five patients cystostomy was performed and they became candidates for delayed treatment. 4. discussion according to our results, the frequency of ugis in this series of cases was 1.9%. the most common injured sites of urogenital system were kidney with 155 (58%) cases, followed by external genitalia with 91 (34.1%) cases. 77.5% of cases were managed conservatively. appropriate data are needed to assess clinical presentation, therapeutic procedure, trauma systems issues, and quality of care for this health problem (19). according to burden of disease and injuries, 28% of years of life lost in iran is attributed to accidents (20). this issue may point out that emergency medical service is not able to provide trauma patients with efficient and perfect pre-hospital care (21). the condition of trauma possibly depends on the space from hospital to high ways, socioeconomic status, grade of hospital as trauma center, and public health infrastructure mainly in prehospital trauma care (22, 23). abundance of construction projects may be the reason that falling down is the second most common cause of injuries. according to the obtained results from this study, ugis comprise a low proportion of injuries in trauma patients (267 of 24742 patients, about 2 %). this is similar to the findings of other studies (10, 14, 24-26). presentations of injured patients were similar to those in the literature. regarding gender, the males enrolled were four times the females, and mainly prevalent in the 3rd decade of life (14, 17, 2729). this may owe to men working in more risky jobs, being more involved in violent behavior and also number of male drivers being more than females (30). most traffic accidents involved middle-aged victims, while the pedestrian accidents involved older age patients. road traffic accidents are the cause of the majority of ugis; trauma had a blunt nature in 92.5% of patients, which is almost similar to other studies (13, 31-34). moreover, kidney was the most common injured organ and kidney repair was the most common surgical treatment in this study. the haemodynamic condition is the point of reference for the diagnostic and therapeutic approach in trauma patients. haemodynamically unstable patients need urgent laparotomy (35). initial treatment of patients with posterior urethral injuries (pui) is one of the most challenging and technically difficult problems in urology (36). the controversy in treatment of pui is surrounding two basically different approaches; one is the insertion of suprapubic cystostomy followed by a delayed urethroplasty; and the other approach is concomitant one stage suprapubic cystostomy and urethral realignment (37, 38). advances in endoscopic techniques have facilitated early realignment and transurethral catheterization as a new treatment approach. in the present study, two thirds of the urethral injury cases underwent primary realignment and the rest became delayed urethroplasty candidates after cystostomy. skin and tissue defects are another problem in patients with trauma. grafts can be utilized for extended skin and tissue defects (39, 40). complete avulsion of the scrotum and penis skin, creates a very serious life-threatening problem. also, there is a serious problem in saving the testes, covering the penis and rehabilitation of area function. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. javanmard et al. 4 there are two types of bladder ruptures: intraperitoneal and extraperitoneal. the extraperitoneal ruptures are often associated with pelvic fractures. intraperitoneal ruptures often happen as a result of frontal impact, with unexpected deceleration while having a full bladder (24). the two most common symptoms of bladder injuries are macroscopic hematuria and abdominal tenderness. other findings consist of inability to void, bruising of the supra-pubic region, and contrast extravasations in computed tomography (ct) urography. pelvic fractures, which are associated with multiple organ injures, including bladder, have a considerable mortality rate (20–40 %) (11, 41). according to our findings, due to the low rate of positive imaging findings in stable trauma patients with microscopic hematuria, it seems that there is no need to routinely perform abdominopelvic ct scan with intravenous contrast in these patients. since most cases with urogenital trauma have multiple injuries, they need a multidisciplinary approach; disregarding these injuries may cause severe complications. we propose establishing an integrated trauma system in iran to improve the quality of trauma care. also, preventive programs aimed at behavioral modifications in the society should be performed to decrease the health and economic burdens imposed by accidents. 5. limitation the first limitation of this investigation is the retrospective nature of the study, which caused some missing medical history and physical examination data. the second limitation is the lack of follow up assessments of disease adjusted life years. 6. conclusion ugis mostly result from blunt trauma due to road traffic accidents. renal injuries are the most common; and ugi mostly develops in youth. conservative management can be the treatment of choice for renal trauma patients who are hemodynamically stable. 7. appendix 7.1. acknowledgements we would like to show our appreciation towards urology and emergency ward staff for their invaluable help throughout this study. we gratefully appreciate medical record department staff of shohada e tajrish hospital for their kind cooperation. we would like to express our sincere gratitude to dr. saeed montazeri for his valuable assistance in english editing of the manuscript. 7.2. author contribution study concept and design: all authors. acquisition of data: dr. fallah-karkan, dr. ghiasi statistical analysis: dr. ghiasy, dr. vafaee. drafting of the manuscript: dr. fallah-karkan, dr. ghiasi and dr. ansari. critical revision of the manuscript: all authors. authors orcids babak javanmard: 0000-0002-0327-8548 morteza fallah-karkan: 0000-0001-8788-2760 mohammadreza razzaghi: 0000-0003-1429-1171 anahita ansari djafari: 0000-0001-6392-1323 saleh ghiasy: 0000-0002-1835-7441 behzad lotfi: 0000-0001-8835-8151 reza vafaee: 0000-0003-0677-4755 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. zou q, fu q. diagnosis and treatment of acute urogenital and genitalia tract traumas: 10-year clinical experience. pakistan journal of medical sciences. 2015;31(4):925. 2. javanmard b. 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drivers involved in traffic accidents. journal of ophthalmic & vision research. 2017;12(4):451. 8. taramsari mr, badsar a, hamrangnejad m, saeidinia a, karkan mf. alcohol intoxication in gilan province this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e63 hospital center of toxicology, iran: demographic, patterns and outcome. archives of advanced sciences. 2017;1(1):10-4. 9. smith gs, barss p. unintentional injuries in developing countries: the epidemiology of a neglected problem. epidemiologic reviews. 1991;13(1):228-66. 10. salimi j, nikoobakht mr, zareei m. epidemiologic study of 284 patients with urogenital trauma in three trauma center in tehran. urology journal. 2009;1(2):117-20. 11. pereira bmt, de campos ccc, calderan tra, reis lo, fraga gp. bladder injuries after external trauma: 20 years experience report in a population-based cross-sectional view. world journal of urology. 2013;31(4):913-7. 12. mcaninch jw. genitourinary trauma. urologic clinics. 2006;33(1):xiii. 13. laal m, khodadadi m, zarei m-r. renal trauma management in 8 cities of iran. acta medica iranica. 2009;47(1):61-4. 14. salimi j, nikoobakht mr, khaji a. epidemiology of urogenital trauma: results of the iranian national trauma project. urology journal. 2009;3(3):171-4. 15. mirzazadeh m, fallahkarkan m, hosseini j. penile fracture epidemiology, diagnosis and management in iran: a narrative review. translational andrology and urology. 2017;6(2):158. 16. allameh f, najafi s, karkan mf, haghighatkhah h, nekuie s. chromophobe renal cell carcinoma presented with wunderlich syndrome. international journal of cancer management. 2017;10(11). 17. sarvestani as, zamiri m. assessment of genitourinary trauma in southeastern iran. trauma monthly. 2013;18(3):113. 18. moore l, clark de. the value of trauma registries. injury. 2008;39(6):686-95. 19. wynn a, wise m, wright mj, rafaat a, wang y-z, steeb g, et al. accuracy of administrative and trauma registry databases. journal of trauma and acute care surgery. 2001;51(3):464-8. 20. zargar m, kalantar motamedi smr, karbakhsh m, ghodsi sm, rahimi-movaghar v, panahi f, et al. trauma care system in iran. chinese journal of traumatology. 2011;14(3):131-6. 21. khashayar p, amoli ha, tavakoli h, panahi f. efficacy of pre-hospital care in trauma patients in iran. emergency medicine journal. 2010;27(6):430-2. 22. zafarghandi m-r, modaghegh m-hs, roudsari bs. preventable trauma death in tehran: an estimate of trauma care quality in teaching hospitals. journal of trauma and acute care surgery. 2003;55(3):459-65. 23. sehat m, naieni kh, asadi-lari m, foroushani ar, malek-afzali h. socioeconomic status and incidence of traffic accidents in metropolitan tehran: a population-based study. international journal of preventive medicine. 2012;3(3):181. 24. paparel p, 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and age distribution in transport-related injuries in tehran. accident analysis & prevention. 2004;36(3):391-8. 30. stiell ig, clement cm, rowe bh, schull mj, brison r, cass d, et al. comparison of the canadian ct head rule and the new orleans criteria in patients with minor head injury. jama. 2005;294(12):1511-8. 31. kuo rl, eachempati sr, makhuli mj, reed ii rl. factors affecting management and outcome in blunt renal injury. world journal of surgery. 2002;26(4):416-9. 32. santucci r, wessells h, bartsch g, descotes j, heyns c, mcaninch j, et al. evaluation and management of renal injuries: consensus statement of the renal trauma subcommittee. bju international. 2004;93(7):937-54. 33. kuan jk, wright jl, nathens ab, rivara fp, wessells h. american association for the surgery of trauma organ injury scale for kidney injuries predicts nephrectomy, dialysis, and death in patients with blunt injury and nephrectomy for penetrating injuries. journal of trauma and acute care surgery. 2006;60(2):351-6. 34. bariol s, stewart g, smith r, mckeown d, tolley d. an analysis of urinary tract trauma in scotland: impact on management and resource needs. the surgeon. 2005;3(1):27-30. 35. aragona f, pepe p, patane d, malfa p, d’arrigo l, pennisi m. management of severe blunt renal trauma in adult patients: a 10-year retrospective review from an emergency hospital. bju international. 2012;110(5):744-8. 36. chapple c, barbagli g, jordan g, mundy a, rodriguesnetto n, pansadoro v, et al. consensus statement on urethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. javanmard et al. 6 thral trauma. bju international. 2004;93(9):1195-202. 37. hadjizacharia p, inaba k, teixeira pg, kokorowski p, demetriades d, best c. evaluation of immediate endoscopic realignment as a treatment modality for traumatic urethral injuries. journal of trauma and acute care surgery. 2008;64(6):1443-50. 38. balkan e, kilic n, dogruyol h. the effectiveness of early primary realignment in children with posterior urethral injury. international journal of urology. 2005;12(1):62-6. 39. brown jb, fryer mp. peno-scrotal skin losses, repaired by implantation and free skin grafting: report of known normal offspring:(preliminary report on total and deep losses). annals of surgery. 1957;145(5):656. 40. karian ls, chung sy, lee es. reconstruction of defects after fournier gangrene: a systematic review. eplasty. 2015;15. 41. wirth gj, peter r, poletti pa, iselin ce. advances in the management of blunt traumatic bladder rupture: experience with 36 cases. bju international. 2010;106(9):13449. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e30 le t t e r to ed i to r information diet in covid-19 crisis; a commentary hasan ashrafi-rizi1∗, zahra kazempour2 1. associate professor, medical library and information science department, health information technology research center, isfahan university of medical sciences, isfahan, iran. 2. library and information science department, faculty of media, payame noor university, tehran, iran. received: march 2020; accepted: march 2020; published online: 22 march 2020 cite this article as: ashrafi-rizi h, kazempour z. information diet in covid-19 crisis; a commentary. arch acad emerg med. 2020; 8(1): e30. 1. introduction by the beginning of covid-19 crisis in china in late 2019, and its spread throughout the world in early 2020, countries around the world experienced numerous problems (1).the outbreak of the new coronavirus started in wuhan, and this third epidemic of coronaviruses expanded to the middle east promptly. . therefore, the world health organization (who) expressed its concerns about the coronavirus crisis (2). this crisis caused production and publication of large amounts of valid and invalid information, eventually leading to information obesity phenomenon. information obesity can have many negative consequences on the general population, causing major problems for governments, especially if the amount of invalid information is too large. it is worth to mention that however almost impossible, controlling and monitoring media is a massive challenge for different governments. hence, individuals should protect themselves against unreliable information, and pursue an authentic "information diet". in the present study, authors have explained and interpreted the concept of the information diet, proposed by johnson, based on scientific evidence, observation of media news and the social media environment, to help maintain the use of valid information in facing the new coronavirus crisis. 2. information diet in crisis condition due to the large amount of information production and publication during the current coronavirus crisis, serious concerns have been raised over people’s excessive information consuming. "if information consumption grows, it can cause a loss of tranquility, confusion and can concern the human mind, rather than being a facilitator of life. therefore, as hu∗corresponding author: hasan ashrafi-rizi; medical library and information science department, health information technology research center, isfahan university of medical sciences, isfahan, iran. email: hassanashrafi@mng.mui.ac.ir, tel: +989132365178. mans respect the limits about use of water, food, and air, they must also rationally limit their consumption of information; otherwise they will encounter phenomena known as the information obesity, and the information diet will be a rational solution to this phenomenon" (3). the concept of information diet was introduced by clay johnson for the first time. he believes consumers should take responsibility for the type of information they consume, likewise the rational consumption of food. he also argues that there must be a sustainable news movement, like a sustainable food movement that has already started in the us. in other words, people and even governments are not capable of dealing with the media to a great extent, but people can create their own information diets, like food diet. therefore, information consumers are advised to consume information in a limited way. however, they must demand complete and credible news, not news that is based on emotional content and full of advertisements" (4). in the present coronavirus crisis, some people spend most of their time studying related information regarding covid-19 in written and virtual media; meanwhile, they are unwilling to spend time exercising at home, talking to their families, playing with their children or doing other useful tasks such as studying, watching movies and so on. to seriously address these problems in the coronavirus crisis, not only people must have optimum consumption of appropriate information, but also consuming information should comply with specific terms and conditions. for example, children should not be exposed to the news related to the coronavirus, because this information increases anxiety and causes other psychological problems among them. the elderly is also vulnerable to the spread of information, and should be provided with reliable and limited information, and they should not be given the ongoing news. on the other hand, individuals should be able to distinguish between high quality and poor quality information, since much of the information regarding covid-19 is invalid and is produced and published for economic, political, social, and in general profitable purposes (disinformation). nowadays, inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ashrafi-rizi and z. kazempour 2 formation is being provided every day, and by contemplating on and reviewing the publication of statistics related to the coronavirus crisis on websites, blogs, social media, television and satellite channels etc., it can be understood that the overload of information has already occurred. hence, providing people with all kinds of health literature is the only option. although people may not have the ability to control the production and supply of the information nowadays, each of them must control the extent and type of the information which they consume. therefore, in order to achieve a comprehensive information diet in societies, people need to be equipped with the knowledge and skills of health information literacy, media health literacy, media literacy and health literacy. currently these trainings can only be delivered through the mass media. delivering these skills requires specific knowledge and skills which health information professionals (medical librarians) poses, and they can train other people in the society through mass media relying on their abilities. 3. conclusion governments need to adopt appropriate policies and plans for managing public opinions in the times of crisis, such as the new coronavirus crisis. the acquisition of "information evaluating skills" by people will be a prerequisite for adhering to the correct information diet, and recommending the information diet as one of the essential strategies in reducing the level of public health anxiety should be considered by health practitioners in countries such as iran. it should be noted that anxiety and confusion, as well as an increase in people’s physical and mental illnesses, including health anxieties and sometimes cyberchondria, are among the negative consequences of not adhering to information diet and consuming more than needed health information. in cyberchondria, an individual searches for a great deal of information, because of inconsistent information and uncertainty about its validity , which in turn will increase one’s anxiety and stress and causes information obesity (5). this phenomenon would be one of the negative consequences of not adhering to the information diet in the current coronavirus crisis. in general, "health media literacy" and public education through mass media are the best options for controlling and monitoring people’s information exposure in the current crisis. certainly, all of the countries need tranquility after overcoming the coronavirus crisis, which will be achieved in the light of people’s adherence to the information diet during and after the crisis. 4. declarations 4.1. acknowledgements authors wish to thank the staffs of health information technology research center, university of medical sciences, isfahan, iran. 4.2. author’s contribution h. a. conceived the original idea, designed the scenarios and collected the data h. a. and h. a., z. k: carried out the analysis of data, approved the final version that was submitted, revised it, h. a., z. k: drafted the manuscript. . a. and z. k met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids hasan ashrafi-rizi: 0000-0001-6052-2087 zahra kazempour: 0000-0001-6834-2814 4.3. conflict of interest the authors have declared that no competing interests exist 4.4. funding and support this research resulted from an independent research without financial support. references 1. ashrafi-rizi h, kazempour z. information typology in coronavirus (covid-19) crisis; a commentary. archives of academic emergency medicine.8(1):19. 2. alavi-moghaddam m. a novel coronavirus (covid-19) outbreak from wuhan city in china, rapid need for emergency departments preparedness and response; a letter to editor. a novel coronavirus (covid-19) outbreak from wuhan city in china, rapid need for emergency departments preparedness and response; a letter to editor. 2020;8(1):1-2. 3. keshavarz h. information seeking: from information needs to information credibility. tehran: ketabdar publishing; 2015. 4. johnson c. the information diet: a case for conscious consumption. usa: o’reilly media; 2012. 5. mcmullan rd, berle d, arnaez s, starcevic v. the relationships between health anxiety, online health information seeking, and cyberchondria: systematic review and metaanalysis. journal of affective disorders. 2019;245:270-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction information diet in crisis condition conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 155 emergency (2015); 3 (4): 155-158 original research non-judicial hanging in guilan province, iran between 2011 and 2013 vahid monsef kasmaee, behzad zohrevandi*, payman asadi, negar shakouri road trauma research center, guilan university of medical sciences, rasht, iran *corresponding author: behzad zohrevandi; road trauma research center, guilan university of medical sciences, rasht, iran. tel: +989188523847. fax: +981313238373; email: bzohrevandi@yahoo.com received: january 2015; accepted: march 2015 abstract introduction: hanging is one of the most commonly used way to commit suicide in many countries. this method used in suicide is considered a problem in iran too, but no clear data exists regarding hanging in different regions or the country as a whole. because of the epidemiologic differences in non-judicial hanging in different regions, this study aimed to assess it in gilan province, iran between 2011 and 2013. methods: in this cross-sectional study, profiles of hanging cases registered in poorsina hospital in gilan, iran between 2011 and 2013 were evaluated. age, sex, marital status, place of residency, level of education, occupation, history of suicide, history of clinical illness, season of suicide and hanging outcome were evaluated. results: 59 cases of hanging (mean age 31.4 ± 13.1 years and 83.0% male) were evaluated. 12 (20.34%) suffered from psychological disorders, and 9 (15.2%) confessed to substance abuse. 7 (11.9%) had a history of suicide attempts by hanging. hanging was significantly higher in men (p<0.001), people with an education level of less than high school diploma (p=0.02) and the unemployed (p<0.05) patients. in the end, 20 (33.9%) of these attempts resulted in death. conclusion: the results of this study showed that in 2 years, 59 cases committed suicide by hanging themselves, 33.9% of which finally died. committing suicide by hanging was significantly more prevalent in men, people with an education level of less than high school diploma and the unemployed. key words: suicide; outcome assessment; hanging cite this article as: monsef kasmaee v, zohrevandi b, asadi p, shakouri n. non-judicial hanging in gilan province, iran between 2011 and 2013. emergency. 2015;3(4):155-8. introduction: uicide is one of the most complex aspects of human life, many features of which is still not fully identified. this phenomenon seems to be restricted to the human race and has not been seen in any other being. it is a conscious move that leads to ending one’s life (14). about 1 million people commit suicide worldwide each year and it is predicted that this number will reach 1.5 million people a year by 2020 (5). world health organization (who) estimates that for each suicide, 10-20 cases of suicide attempt occurs with the most prevalence in the youth and women (6). in iran, the rate of suicide has changed from 1.3 in 100,000 people in 1984 to 6.4 in 100,000 people in 2003 (7). also estimations in 19 provinces of iran have shown that in the 10-14 age group, for each recorded suicide there has been 80 cases of suicide attempt (8). hanging is one of the most commonly used methods for suicide as it is a simple but effective way. as gunnellet et al. have expressed, the mortality rate is at least 70% (9). a study based on the data from who in 56 countries showed that 53% of the suicides in men and 39% in women is by hanging. in england and wales, about half of the suicides in men aged 15-44 are carried out this way. in iran, reports by forensic service showed that the most common method used among men who died from suicide was hanging (56.05%) (10). though the prevalence of this method is low compared to other countries such as the united states, it is still high. it is considered a problem in iran’s health system but no clear data exists regarding hanging in different regions or the country as a whole (11-13). because of the mentioned points and the epidemiologic differences in non-judicial hanging in different regions, this study aimed to assess non-judicial hanging in guilan, iran between 2011 and 2013. methods: this cross-sectional study assessed the epidemiological pattern of suicide cases with the hanging method who were admitted to poorsina hospital, rasht, iran from 2011 to 2013. the study protocol has been approved by s this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com monsef kasmaee et al 156 the ethics committee of guilan university of medical sciences. the patients have participated voluntary and the written consent form was signed by either the patient or their guardian. the researchers abided by the principles of helsinki convention over the course of the research and patients’ data were kept confidential. all the patients that had attempted to hang themselves were included. exclusion criteria included not willing to take part in the study and judicial hanging. data were gathered using a checklist. age, sex, marital status, place of residency, level of education, occupation, history of suicide, history of illness, season of suicide, hanging outcome (death or survived). the data were gathered by a physician who had been trained to fill out medical research checklists. sample size was calculated to represent the general population on the basis of 50% hanging resulted in death, 10% precision, and 95% confidence interval. thus, sample size was estimated at 49. data were analyzed using spss 21.0. quantitative data were reported as mean ± standard deviation and qualitative data were expressed as frequency and percentage. in evaluating the relationship between sex, marital status, level of education, place of residency, and occupation with committing suicide, multinomial logistic regression test was used. in the end, to assess the relationship between the outcome (death or survived) with the demographic characteristics, mann-whitney (for quantitative and ordinal qualitative data), chi square and the fisher exact test (for nominal qualitative data) were used. p < 0.05 was considered as significance. results: finally, 59 cases of hanging were referred to the hospital. mean age of the patients was 31.4 ± 13.1 years (age range of 12-80 years). 83% were male. 30 (50.8%) patients were married and 35 (64.3%) cases lived in the city. 12 (20.34%) patients suffered from psychological disorders, and 9 (15.2%) patients confessed to substance abuse. 7 (11.9%) subjects had a history of committing suicide and 22 (37.3%) of the suicide attempts were done in fall (tables 1 and 2). suicide attempts by hanging was significantly higher in men (p<0.001), people with an education level of less than high school diploma (p=0.02), and the unemployed (p<0.05). in the end, 20 (33.9%) cases of these attempts resulted in death. table 3 shows the relationship between demographic factors of the patients with suicide outcome. none of these factors had any correlation with the outcome (p > 0.05). discussion: the results of this study showed that in 2 years, 59 people attempted suicide by hanging. hanging was more prevalent among men, people with an education level of less than high school diploma and the unemployed patients. in the end 33.9% of these attempts resulted in death. hanging is a way of suicide with a mortality rate of at least 70% as gunnellet et al. have shown. these researchers stated that the reason for the high prevalence of this method is that the materials for hanging are highly accessible. therefore it is considered a method which is hard to prevent (9). akhlaghi et al. express that hanging constitutes 22.1% of suicide deaths (14). in the present study, mean age of patients was 31.4 years, half of which were under 28 years old. 83.1% were male which means the frequency of suicidal males has been 5 times more than the females. sharija et al. have also shown that 71.3% of the suicide by hanging cases were male and 82.1% were either young or middle aged (15). a study based on the data from who in 56 countries showed that 53% of the suicides in men and 39% in women is by hanging. in england and wales, about half of the suicides in men aged 15-44 are carried out this table 1: demographic and basic factors of the patients included factor frequency (%) p sex female 10 (17.0) male 49 (83.0) <0.001 marital status single 30 (50.8) married 29 (49.2) 0.9 place of living rural area 23 (39.7) the city 35 (60.3) 0.12 level of education under diploma 37 (64.9) high school diploma 20 (35.1) 0.02 occupation unemployed 27 (49.1) worker 14 (25.4) 0.04 student 6 (10.9) 0.001 self-employed 6 (10.9) 0.001 retired 2 (3.6) <0.001 table 2: factors related to suicide in the studied patients substance abuse status frequency (%) negative 50 (84.8) positive 9 (15.2) history of psychological disorders negative 47 (79.7) positive 12 (20.3) history of suicide negative 52 (88.1) positive 7 (11.9) season spring 13 (22.0) summer 13 (22.0) fall 22 (37.3) winter 11 (18.7) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 157 emergency (2015); 3 (4): 155-158 way (14). also höfer et al. showed that the ratio of suicide by hanging in men and women is 7 to 1 (16). the prevalence of psychological disorders in this study was 20.3%. the prevalence of psychological disorders in iran in cities and rural areas were 20.9% and 21.3%, respectively (17). therefore, there is no different between our study and the national average rate for general population. however, the prevalence of substance abuse in iran has been reported to be 4-7% (18-20). in this study, the prevalence of substance abuse was 15.2%, which was about twice the national average rate for general population. this result is in line with those of similar studies which express that suicide is more prevalent in people with substance use disorders (21, 22). limitations of this study include the low number of cases, which was due to the nature of the subject of study and the low number of hanging cases that reach the hospital. other limitations include not evaluating the clinical characteristics and medical interventions, history of alcohol abuse, and type of opium abused. conclusion: the results of this study showed that in 2 years, 59 cases committed suicide by hanging themselves, 33.9% of which finally died. committing suicide by hanging was significantly more prevalent in men, people with an edutable 3: the relationship between the patients’ demographic and basic factors with their suicide outcome factor outcome p death survived sex male 17 (34.7) 32 (65.3) 0.99 female 3 (30.0) 7 (70.0) marital status single 11 (36.7) 19 (63.3) 0.65 married 9 (31.0) 20 (69.0) place of living rural area 8 (34.8) 15 (65.2) 0.97 the city 12 (34.3) 23 (65.7) level of education less than high school diploma 9 (45.0) 11 (55.0) 0.25 high school diploma 11 (29.7) 26 (70.3) occupation unemployed 10 (37.0) 17 (63.0) 0.36 worker 5 (35.7) 9 (64.3) student 3 (50.0) 3 (50.0) self-employed 0 (0.0) 6 (100.0) retired 1 (50.0) 1 (50.0) substance abuse status negative 19 (38.0) 31 (62.0) 0.12 positive 1 (11.1) 8 (88.9) history of psychological disorders negative 16 (34.0) 31 (66.0) 0.96 positive 4 (33.3) 8 (66.7) history of suicide negative 0 (0.0) 7 (100.0) 0.08 positive 20 (38.5) 32 (61.5) season spring 5 (38.5) 8 (61.5) 0.18 summer 7 (53.8) 6 (46.2) fall 4 (18.2) 18 (81.8) winter 4 (36.4) 7 (63.6) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2015 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com monsef kasmaee et al 158 cation level of less than high school diploma, and the unemployed conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for 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[persian]. 21. fowler rc, rich cl, young d. san diego suicide study: ii. substance abuse in young cases. arch gen psychiatry. 1986;43(10):962-5. 22. kim hm, smith eg, stano cm, et al. validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use. bmc health serv res. 2012;12(1):18-22. introduction: methods: results: discussion: conclusion: conflict of interest: funding support: authors’ contributions: references: archives of academic emergency medicine. 2020; 8(1): e49 rev i ew art i c l e analysis of maternal coronavirus infections and neonates born to mothers with 2019-ncov; a systematic review salut muhidin1, zahra behboodi moghadam2, maryam vizheh2∗ 1. department of management, macquarie business school, macquarie university, new south wales, 2109, australia. 2. department of reproductive health and midwifery, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 15 april 2020 abstract: introduction: the emergence and fast spread of 2019 novel coronavirus (2019-ncov ) threatens the world as a new public health crisis. this study aimed to clarify the impact of novel coronavirus disease (covid-19) on pregnant patients and maternal and neonatal outcomes. methods: a comprehensive literature search was conducted in databases including pubmed, scopus, embase, proquest, and science direct. all studies including original data; case reports, case series, descriptive and observational studies, and randomized controlled trials were searched from december 2019 until 19 march 2020. results: the search identified 1472 results and 939 abstracts were screened. 928 articles were excluded because studies did not include pregnant women. full texts of eleven relevant studies were reviewed and finally nine studies were included in this study. the characteristics of 89 pregnant women and their neonates were studied. results revealed that low-grade fever and cough were the principal symptoms in all patients. the main reported laboratory findings were lymphopenia, elevated c-reactive protein (crp), amino alanine transferase (alt), and aspartate amino transferase (ast). in all symptomatic cases, chest computerized tomography (ct) scans were abnormal. fetal distress, premature rupture of membranes and preterm labor were the main prenatal complications. two women needed intensive care unit admission and mechanical ventilation, one of whom developed multi-organ dysfunction and was on extracorporeal membrane oxygenation (ecmo). no case of maternal death was reported up to the time the studies were published. 79 mothers delivered their babies by cesarean section and five women had a vaginal delivery. no fetal infection through intrauterine vertical transmission was reported. conclusions: available data showed that pregnant patients in late pregnancy had clinical manifestations similar to non-pregnant adults. it appears that the risk of fetal distress, preterm delivery and prelabor rupture of membranes (prom) rises with the onset of covid-19 in the third trimester of pregnancy. there is also no evidence of intrauterine and transplacental transmission of covid-19 to the fetus in the third trimester of pregnancies. keywords: covid-19; severe acute respiratory syndrome coronavirus 2 (sars-cov-2); pregnancy outcome; infectious disease transmission, vertical; infant, newborn; systematic review cite this article as: muhidin s, behboodi moghadam z, vizheh m. analysis of maternal coronavirus infections and neonates born to mothers with 2019-ncov; a systematic review. arch acad emerg mede. 2020; 8(1): e49. 1. introduction the emergence and fast spread of 2019 novel coronavirus (2019-ncov ) threatens the world as a new public health crisis (1). severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is a member of the coronavirus family, whose members cause a range of infectious diseases from a common cold to severe acute respiratory syndrome (sars) and ∗corresponding author: maryam vizheh; department of reproductive health and midwifery, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. email: maryamvizheh@yahoo.com the middle east respiratory syndrome (mers) (2). at the moment, there is very limited knowledge about the various aspects of the disease including pregnancy and maternal and fetus health. epidemic and pandemic viral infections in recent years have shown that pregnant women experience more adverse outcomes than non-pregnant ones (2). the risk of developing a viral infection, including sarscov, mers-cov, ebola, h1n1, and influenza-a is higher in pregnant women, and these infections can lead to undesirable medical and prenatal outcomes such as maternal mortality, spontaneous abortion, stillbirth and preterm delivery. however, we know little about covid-19 in pregnancy (3). pregnancy-related immunological and physiologthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. muhidin et al. 2 ical changes that naturally occur during pregnancy can lead to worsening of respiratory infections due to systemic effects on the body. increased heart rate, oxygen consumption, stroke volume, and decreased pulmonary capacity and functional residual capacity are the main physiological changes in the cardiovascular and respiratory systems during pregnancy that increase the complications of covid-19 in pregnant women compared to the non-pregnant population (2, 4). on the other hand, pregnancy is associated with immunosuppression. this situation makes pregnant women more susceptible to infectious diseases (2). moreover, there is a possibility of vertical transmission of sars-cov-2 from mother to fetus and creating significant infections in fetuses and neonates (2). these concerns are based on experiences gained from infections such as the zika virus, ebola virus, marburg virus and other agents capable of transmitting vertically from mother to fetus. these viruses could threaten the health and survival of the infected mother and her fetus (4). currently, the clinical attributes and vertical transmission capability of covid-19 in pregnant patients are obscure. this raises questions about covid-19 in pregnancy. these questions include: are the symptoms of covid-19 infection different in pregnant women compared to the general population? are pregnant women with covid-19 pneumonia at a higher risk of death? are pregnant women with covid-19 pneumonia at higher risk of obstetrics complications such as preterm labor and low birth weight? can infection transmit vertically and cause fetal and neonatal disease? therefore, it is crucial to find answers to these questions to gain insight and design a management protocol for pregnant women. so, this study was designed to investigate the impact of covid19 on pregnant women and their infants. moreover, assessing the risk of vertical transmission and the possible mechanisms of infection transmission from mother to fetus were other aims of this review. 2. method 2.1. study design and search strategy this study is a systematic review conducted to identify the research studies that addressed the impact of covid-19 in pregnancy. since, this emerging pneumonia was first reported from china in december 2019, a comprehensive literature search was conducted in databases from its inception in december 2019 until 19 march 2020. all studies including original data; case reports, case series, descriptive, observational and randomized controlled trials were included. searching articles was carried out using related keywords in several international electronic databases, namely: pubmed, scopus, embase, proquest, and science direct. additionally, a manual search was performed in google scholar. references of the included studies were reviewed manually. the article search was performed using the keywords: "covid-19 or sars-cov-2 or novel coronavirus and pregnancy or prenatal or neonatal or fetus". some of search strategies were: "covid-19"[all fields] or "severe acute respiratory syndrome coronavirus 2"[supplementary concept] or "severe acute respiratory syndrome coronavirus 2"[all fields] or "2019-ncov"[all fields] or "sars-cov-2"[all fields] or "2019ncov"[all fields] or (("wuhan"[all fields] and ("coronavirus"[mesh terms] or "coronavirus"[all fields])) and ("pregnancy"[mesh terms] or "neonatal"[all fields]). the selection process of the studies is represented in fig. 1. 2.2. selection criteria inclusion criteria were: articles published in english or persian language that contained the keywords in their title, abstract or keywords, and their full-text was available. articles that addressed neonates without providing a detailed perinatal history of their mothers, articles of pregnant patients without reporting perinatal data and outcomes and articles in other languages were excluded. moreover, to avoid overlapping in data, systematic reviews were excluded. 2.3. study selection and data extraction primary research articles that assessed various aspects of covid-19 in pregnancy were included in this study. the initial database searching and screening the titles and abstracts were performed by one author (mv ). then these articles were classified as: relevant, irrelevant or unsure. all authors (sm, zb, and mv ) assessed every single article classifying them as relevant or unsure, independently. once all relevant articles were identified, all authors reviewed full texts of all identified articles and extracted the data. after completing primary data extraction, all authors assessed the content of retrieved data. the following data were obtained from each included study: characteristics of the study including first author’s name, setting and date of publication, eligibility criteria, and sample size; details on patients including demographic, epidemiological, clinical and para-clinical manifestations, prenatal complications, maternal and fetal outcomes, and adverse effects related to covid-19, were extracted from the included articles using a pre-defined data extraction checklist, developed by authors. once data extraction was complete, the authors reviewed the obtained data and summarized them. 2.4. methodological quality (risk of bias) assessment quality assessment tools of the national institutes of health (nih) consisting of 9 items for case-report studies and 12 items for case-control studies were used to assess the quality and risk of bias of included studies by two authors (zb, mv ), independently (5, 6) (table 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e49 figure 1: flow chart of the study’s selection process based on prisma. 2.5. outcome of interest the clinical manifestations of pregnant mothers with covid-19, the risk of death, the possibility of vertical transition of infection and obstetrics and neonatal outcomes of covid-19 were the studied outcomes in this systematic review. 2.6. statistical analysis spss version 16 was used for analyzing data. categorical variables are expressed as number (%) and continuous variables are expressed as ranges. 3. results the search yielded 1472 results and 939 abstracts were screened. 928 articles were excluded because the studies did not include pregnant women. full texts of eleven relevant studies were reviewed. after assessing full-texts, two studies were excluded. one of them was excluded because the mother’s data was reported in another case series. another study that reported "clinical, and ct imaging features this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. muhidin et al. 4 table 1: characteristics, objectives and outcomes of included articles row author[ref ] setting date of publication design objective (s) main outcome(s) 1 chen et al. (7) china feb 12, 2020 retrospective a) assessing the clinical attributes of a) covid-19 pneumonia in case series covid-19 in pregnancy b) assessing the risk of vertical transmission of covid-19 infection pregnant women showed attributes similar to non-pregnant adult patients b) there is yet no evidence for intrauterine vertical transmission of covid-19 from mother to fetus 2 zhu et al. (8) china feb 10, 2020 retrospective assessing clinical manifestation of a) there is a possibility of adverse case series 10 neonates born to mothers with covid-19 pneumonia effects of perinatal covid-19 infection on newborns such as premature labor, fetal distress, respiratory distress, thrombocytopenia due to abnormal liver function, and death b) vertical transmission of covid-19 is not currently reported. 3 li et al. (9) china 2020 case-control assessing maternal and neonatal a) there was no evidence that study outcomes of pregnant women with covid-19 pneumonia covid-19 pneumonia is accompanied with severe maternal and neonatal complications b) considering the delay in receiving pcr tests, in the third trimester of pregnancy, especially in epidemic areas, chest ct scans can be an effective way of screening for covid-19 pneumonia 4 liu et al. (10) china feb 2020 case series clinical symptoms and outcomes of covid-19 infection in pregnant patients covid-19 infection can pose a threat to maternal and neonate’s health 5 fan et al. (2) china 2020 case report assessing perinatal transmission of covid-19 a) perinatal outcomes were uneventful b) the risk of vertical transmission of covid-19 is trivial 6 chen et al. (11) china 16 mar 2020 case series assessing the safety of general or epidural anesthesia in pregnant patients with covid-19 a) both general and epidural anesthesia could be applied safely in pregnant patients with covid-19 undergoing cesarean section b) there was a higher rate of hypotension during epidural anesthesia 7 wang (3) china 2020 case report explaining a case of preterm delivery in a pregnant woman with coronavirus neonate was unaffected by covid-19 8 liu et al. (12) china 25 feb2020 case series assessing the outcomes of covid-19 during pregnancy a) perinatal outcome in both mothers and infants was uneventful b) there was no evidence of vertical transmission 9 song et al. (13) china, 2020 case report explaining anesthetic management of a parturient with covid-19 applying both epidural and spinal anesthesia provided effective anesthesia. of covid-19 pneumonia" in seventeen pregnant mothers was also excluded due to lack of information on obstetrics and perinatal data of patients (figure 1). all nine included studies that reviewed pregnant women and their infants are summarized in table 1. overall, in these nine studies, 89 pregnant women were studied, 68 of which were confirmed to have covid-19 pneumonia through positive result of rt-pcr for sars-cov-2 and eighteen were suspected cases admitted to hospital for their symptoms or labor. three mothers were discharged with an uncomplicated ongoing pregnancy. moreover, the characteristics of 89 neonates born to 86 infected mothers singletons and three sets of twins) were studied. the overall risk of bias in the included studies was low (table 2). two of the seven case-report studies failed to adequately follow up patients (11, 12). in all studies except for 2, the statistical method was either not reported or did not need to be reported. in the case-control study, the process of choosing sample size this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e49 table 2: quality assessment of included studies quality assessment tool for case control studies author[ref ] year(all 2020) item 1 item 2 item 3 item 4 item 5 item 6 item 7 item 8 item 9 item 10 item 11 item 12 1 li et al. (9) © © § © § © § © na © a § quality assessment tool for case series studies author[ref ]; year(all 2020) item1 item 2 item 3 item 4 item 5 item 6 item 7 item 8 item 9 2 chen et al. (7) © © © © © © © © © 3 zhu et al. (8) © © © © © © © na © 4 liu et al. (10) © © © © © © § § © 5 fan et al. (2) © © a © © © © na © 6 chen et al. (11) © © © © © © a © © 7 wang et al. (3) © © na na © © © na © 8 liu et al. (12) © © © © © © © na © 9 song et al. (13) © © na na © © © na © ©: low risk; §: high risk; a: unclear risk; na: not applicable and adjustment of confounding variables was not clear (9). to more focus on the objectives and topics discussed in the articles, the results of this review will be presented in several sections. 3.1. clinical features, diagnosis, and treatment based on data retrieved from relevant articles, pregnant patients ranged from 22 to 40 years old. all women were in the third trimester of pregnancy. fever and cough were the dominant and principal symptoms in all patients. but in none of them did the temperature rise above 39 degrees. fever was low-grade in all patients. fatigue, dyspnea, and sore throat were less common symptoms. also, three women reported gastrointestinal symptoms such as diarrhea or vomiting. between 18 to 100 percent of the patients in any individual study and overall, 40 patients had a clear history of epidemiological exposure to covid-19, either exposure to the relevant environment or contact with an infected person. one study did not provide a history of how patients were infected (9).the time interval between onset of symptoms to delivery varied from 15 days before to 3 days after delivery. diagnosis of covid-19 in the mentioned studies followed the standard protocol, like non-pregnant patients. for this purpose, clinical symptoms, history of exposure to infection, laboratory results, computed tomography (ct) evidence of pneumonia and typical signs of viral infection were considered and eventually all cases were confirmed via quantitative rt-pcr (real-time reverse transcription-polymerase chain reaction) on sars-cov-2. in all studies, maternal throat swab samples were collected and tested for sars-cov-2 with the kit (biogerm, shanghai, china) recommended by chinese center for disease control and prevention (cdc) following who guidelines for qrt-pcr (8). laboratory findings such as lymphopenia (n=19), elevated c-reactive protein (n=29); alanine aminotransferase (alt) and aspartate aminotransferase (ast) (n=3) and decreased albumin (n=1) were reported in most studies. in all symptomatic cases, chest ct scans revealed abnormal viral changes in lungs demonstrating lungs with patchy ground-glass shadows. oxygen therapy, antiviral and antibiotic therapy was prescribed as standard treatment based on each patient’s condition. additionally, two patients were admitted to intensive care unit (icu), and one patient was on extracorporeal membrane oxygenation (ecmo). 3.2. obstetric characteristics and outcomes previous medical history of patients revealed that 30 mothers had a history of other comorbidities before the infection with covid-19 including hypertension (htn) (n=5) (7, 9, 11), preeclampsia (n=2) (7, 9), influenza (n=1) (7), vaginal bleeding in the third trimester (n=2) (2, 8), hypothyroidism (n=3) (9, 12), polycystic ovary syndrome (n=3) (9), hepatitis b (n=3) (9), gestational diabetes mellitus (n=6) (9, 11, 12) and anemia (n=5) (11). in the study by li et al., around 70% had other maternal complications, which was significantly higher than the control group (31-33%). all these complications were developed before diagnosis of pneumonia (9). moreover, fetal distress (n=15) (7-10, 12), prelabor rupture of membranes (prom) (n=6) (7-9), preterm labor (n=30) (2, 3, 7-11, 13), abnormal umbilical cord (n=2) (8), stillbirth (n=1) (10), placenta previa (n=1) (8), abnormal af (n=2) (8), placental abruption (n=1) (9) were the most commonly reported complications. one study with 17 samples did not provide complete details on maternal or neonatal complications (11). in the study by chen et al., six of the nine studied women had postpartum fever (7). furthermore, in the study by li et al., eight of the 16 patients with confirmed covid-19 pneumonia and six of the eighteen suspected cases reported postpartum fever, 50.0%, and 33.3%, respectively(9). two women were admitted to the icu and required mechanical ventilation, one of whom developed multi-organ dysfunction. up to the time of publishing the study, the mentioned patient was on extracorporeal membrane oxygenation (ecmo) (3, 10). no cases of maternal death were reported up to the time this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. muhidin et al. 6 the studies were published. 3.3. mode of delivery fear and uncertainty about the risk of vertical transmission of infection during vaginal delivery, have made confirmed or suspected covid-19 pneumonia an indication for cesarean section in china since 24 january 2020(5, 9). in the reviewed papers, 79 of 86 mothers delivered their babies by cesarean section. although the main indication of cesarean section was covid-19, fetal distress (n=11) (7, 8, 10), pre-eclampsia (n=1) (7), a history of c-section (n=2) (7, 13), premature rupture of the membrane (n=7) (7, 8, 10), stillbirth and a history of stillbirth (n=2) (10), abnormal amniotic fluid (n=2) (8), abnormal umbilical cord (n=2) (8), abnormal placenta (n=1) (8), persistent fever (n=1) (2), and admission to the intensive care unit (icu) (n=1) (3), were additional indications that led to caesarean section, especially emergency cesarean section. five of the patients had natural vaginal delivery (8, 9, 12). two of them had natural vaginal delivery (nvd) because during admission for full-term labor they did not show any respiratory symptoms. one of them developed fever two days after childbirth and in another patient, on the same day of labor ct images of right lung changed to the patchy shadows (9). moreover, one normal vaginal delivery was performed due to maternal request (12). 3.4. vertical transmission potential of covid-19 infection in a study conducted by chen et al. for assessing the possibility of vertical transmission, they examined amniotic fluid, umbilical cord blood, breast milk samples and neonatal throat swab in nine pregnant women with covid-19 pneumonia and they concluded that there is no evidence of vertical transmission of sars-cov-2 infection (7). moreover, liu et al. carried out further assessments by examining placenta tissue and vaginal mucus and did not report any infected neonates (10). also, the findings of studies carried out by fan et al. and song et al. are consistent with these results (2, 13). although in other studies, researchers did not evaluate the products of conception, by evaluating throat swabs of neonates born to these infected mothers, they reported that in all neonates, qrt-pcr was negative. therefore, they claimed that there was no evidence of intrauterine transmission of infection. to date, none of the studies has reported neonatal infection acquired from pregnant women with covid-19 pneumonia. 3.5. neonates’ outcomes data of 89 neonates was included in this review. the range of fetal weight was 1520–3820 grams. seven infants were born with low birth weight. also, two infants were small-forgestational-age (sga), and one was large-for-gestational-age (lga) (8). none of the neonates received antiviral treatment. the results of qrt-pcr proved that none of the neonates were infected with covid-19. death of two neonates was reported (8, 12). there is a wide range of neonatal symptoms reported in these studies. zhu et al. examined 10 neonates born to mothers with covid-19 pneumonia comprehensively, nine of whom showed symptoms after birth. shortness of breath in 6 cases, fever in 2, and tachycardia in one neonate were reported (8). furthermore, four of ten neonates in one study showed a range of gastrointestinal symptoms such as gastric bleeding, feeding intolerance, refusing milk and bloating (8). seven neonates had abnormalities in chest radiography at the time of admission, which were caused by infections (n=4), neonatal respiratory distress syndrome (nrds) (n=2), and pneumothorax (n=1). refractory shock was found in one of the neonates, which developed into multiple organ failure and disseminated intravascular coagulation (dic). as a result, treatment started with platelet transfusion, suspended red blood cells, and plasma. however, he died nine days after birth. another neonate received intravenous transfusion of gamma globulin, platelets, suspended red blood cells, and plasma. up to the date of publishing the report, this infant was alive (8). both of the two neonates reported by fan et al. (2), showed complications after birth. one of them had lymphopenia, abdominal distension and low-grade fever three days after birth and diffuse haziness in chest radiograph four days after birth. however her response to the antibiotic was good and she was later discharged. the other neonate had lymphopenia (10.5%) and mild neonatal pneumonia and was treated with antibiotics and was also discharged from the hospital (2). moreover, a 40-week baby developed meconium stained amniotic fluid and chorioamnionitis as a result of chronic fetal distress (12). other neonates did not show any adverse outcomes. additionally, breastfeeding was prohibited in all cases, and infants were fed with formula. 4. discussion data retrieved from included studies revealed that pregnant women with covid-19 showed symptoms similar to those reported in non-pregnant adults. in the current study, the most dominant initial symptoms were fever and cough. however, there wasn’t any high-grade fever. in all patients complaining of fever, the temperature was less than 39 ◦c. this is consistent with the results of non-pregnant patients. one meta-analysis reviewed data of 46248 infected patients with covid-19 and reported that in the general population, the principal clinical symptoms were fever (91±3, 95%ci 8697%), cough (67±7, 95% ci 59-76%), fatigue (51±0, 95% ci 34-68%) and dyspnea (30±4, 95% ci 21-40%) (14). similarly, previous studies focusing on sars and mers revealed that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e49 laboratory and clinical findings in pregnancy were similar to those reported in the general population (15). this study also found that the rate of developing severe pneumonia and the need for admission to icu were relatively low and similar to the non-pregnant cases. only two of the 86 pregnant women in this study developed severe pneumonia. however, there was not any report of maternal death. the limited data available on the effects of sars and mers in pregnancy, proposes that the complications of covid-19 in pregnancy are lower than other coronaviruses. a review on sars in 12 pregnancies revealed a case-fatality rate of 25%. acute respiratory distress syndrome (ards) (n=4), disseminated intravascular coagulopathy (n=3), renal failure (n=3), secondary bacterial pneumonia (n=2), and sepsis (n=2) were the main complications (15). in pregnant women infected with sars, mechanical ventilation was three times more common than nonpregnant cases. on the other hand, in a study on 13 pregnant cases with mers-cov, three patients (23%) died (15). the standard protocol for diagnosis of covid-19 is using real-time polymerase chain reaction (rt-pcr). samples can be obtained from the upper respiratory tract (nasopharyngeal and oropharyngeal swabs, saliva) or the lower respiratory tract (sputum, endotracheal aspirate or bronchoalveolar lavage) as well as urine and stool. if required, samples should be repeated to confirm the diagnosis. covid-19 can be ruled out if two consecutive samples from the respiratory tract with at least 24 hours interval are negative. using serology as a diagnostic procedure is recommended only when rt-pcr is not available (16). however, li et al. suggested that chest ct scans in the third trimester in pregnant women could be an effective test to assess covid-19 pneumonia given the strained time and availability of pcr tests, especially in regions struggling with ongoing epidemics (9). data reported from other similar viral infections such as sars, mers, and influenza in previous studies showed that these infections could compromise pregnancies. the rate of poor fetal outcomes, abortion, and miscarriage was significant. also, the outcomes of pregnant patients were more undesirable than the general population (2). in a study, 10 out of 11 pregnant mothers infected with sars-cov, revealed adverse outcomes. their neonates also showed complications such as admission to neonatal icu (nicu) (n=6, 55%) and death (n=3, 27%). moreover, two neonates were born prematurely due to severe maternal respiratory failure. outcomes of pregnancies depended on trimesters of pregnancies. fullterm healthy infant (n=1), spontaneous abortion (n=4) and elective termination of pregnancy (n=2) due to social reasons after recovery from sars were the outcomes of seven pregnant mothers infected with sars in the first trimester (16). four preterm labor deliveries with gestational age after 24 weeks were also reported by studying five women (15). similarly, results acquired from 13 pregnant patients with merscov showed two preterm labors and two fetal demises. evidence of vertical transmission was neither detected in sars nor in mers (15). however, the limited sample size of pregnant patients infected by covid-19 found that the behavior of this virus in pregnancy is different. although the rate of preterm labor and fetal distress was significant, fewer adverse maternal and neonatal outcomes and complications have been reported due to covid-19 infection in pregnancy (17). until now, there is no report on the death of pregnant women in articles. there are some reasons for these differences. first of all, the number of cases in these studies is small. secondly, all women were in their third semester of pregnancy and most of them gave birth less than seven days after the diagnosis of the disease. hence, this short clinical manifestation-to-delivery time may be too short to affect pregnancies. the preferred mode of delivery in cases reported in this review was cesarean section and only five women (6%) delivered vaginally; none of whose neonates was infected with covid-19. intrapartum transmission was the main concern for choosing cesarean section. since there is limited evidence about vertical transmission and vaginal shedding of virus, vaginal delivery in stable patients may be considered. in cases of cesarean section, the choice of anesthesia needs careful consideration (16). favre et al. suggested that for every individual patient, vaginal delivery even by induction should be considered. using instrumental delivery also is preferred to cesarean section to avoid unnecessary surgical complications and maternal exhaustion (18). the main objective of 3 of the 9 original articles included in this review was evaluating the possibility of vertical transmission of covid-19 in pregnancy. the authors attempted to examine conception products, namely samples of amniotic fluid, cord blood, breast milk, placenta tissue, and vaginal mucus, and assessed rt-pcr results in neonates to answer this critical question. however, neither these samples nor neonates were infected with covid-19. the most significant point is that all samples were collected during parturition in the operating room. this can ensure that none of the samples were contaminated and also represent the real intrauterine conditions (19). these articles suggested that the possibility of vertical transmission of infection in pregnant women with covid-19 pneumonia in late pregnancy is trivial. however, these results could be affected by small sample size, mode of delivery and gestational age at the time of infection (20). serious suspicion to the presence of the virus in body secretions led to a study conducted by cui et al. to explore the possibility of sexual transmission of covid-19. they analyzed vaginal environment samples such as vaginal discharge and cervical or vaginal residue exfoliated cells as well as anal swab samples in 35 female patients using rt-pcr to detect sars-cov-2 (21). only one anal swab sample was positive this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. muhidin et al. 8 for sars-cov-2. all the samples acquired from vaginal surroundings were negative for sars-cov-2. they suggested that this could be due to the absence of sars-cov-2 receptor (ace2 expression) in vagina and cervix tissues (21). although most of the neonates included in this study did not have any adverse outcomes, the results of the study by zhu et al. indicated that perinatal covid-19 infection can cause adverse neonatal outcomes including preterm labor, thrombocytopenia due to abnormal liver function, fetal distress and respiratory distress (8). these results are consistent with neonatal consequences in sars and mers infections (15). 4.1. implications of covid-19 for pregnant women during this extremely delicate time of a rapidly evolving outbreak that has imposed a tremendous threat on public health, more attention should be given to the unique needs of pregnant women (15). further investigation and isolation should be considered for pregnant women with suspected covid-19. in confirmed cases, prompt admission of mothers in a negative pressure isolation unit is crucial (16). all the medical staff responsible for taking care of covid19 patients should utilize personal protective equipment, namely n95 masks, gloves, gown, and goggles. standard protocol of the management of covid-19 in pregnancy incorporates early isolation, controlling infection, administrating oxygen, detecting other viral infections, applying early mechanical ventilation in patients with progressive respiratory failure, and administrating antibiotics in cases of risk of bacterial infection. monitoring of fetus and uterine contraction should be considered. any planning on delivery of the patients and their conditions should be made through multispecialty consultations (15). ensuring sufficient rest, fluid and electrolytes balance and nutritional support is important. oxygen saturation and vital signs should be carefully monitored. considering the level of hypoxemia, supplemental oxygen (60%-100% concentration at a rate of 40 l/min) through high-flow nasal cannula should be administered. in critical cases, mechanical ventilation or even ecmo may be required for ensuring oxygenation (16). in critical cases, pregnancy can put the mother and fetus in danger. therefore, in these cases, early termination of pregnancy is necessary even in premature pregnancies. this situation needs careful consultation with the patient, her family, and an ethical board. it is also essential that pregnant women avoid unnecessary travel, public transport, crowds, and close contact with patients. above all, maintaining personal and social hygiene is vital (16). 5. conclusion in conclusion, available data revealed that clinical manifestations of pregnant women in late pregnancy are similar to those of non-pregnant adults. there is also no evidence that pregnant women are at higher risk of developing covid-19 infection or are susceptible to severe pneumonia. considering the negative results of sars-cov-2 in samples of umbilical cord blood, amniotic fluid, breast milk, vaginal mucus, placenta tissue, and neonatal throat swab, there is also no evidence of intrauterine transmission of covid-19 infection in the third trimester of pregnancies. it appears that the risk of fetal distress, preterm delivery and premature rupture of membranes rises when covid-19 onsets in the third trimester of pregnancy. since there are no reports of pregnant patients in the first or second trimesters of pregnancy, the risk of stillbirth and abortion as a result of covid-19 is obscure and needs to be clarified. given the impact of similar infections (sars and mers) on outcomes of pregnancies in the first and second trimesters, further studies are needed to evaluate the long-term effects of covid-19 on pregnancy and neonate outcomes. overall, due to the lack of information on covid-19 pneumonia in pregnancy, all suspected pregnant women should be systematically screened, monitored and followed up. another issue is whether natural vaginal delivery increases the likelihood of vertical transmission of the infection and if so, the possible mechanisms need to be clarified. further investigations and follow-up studies of pregnant mothers infected by covid-19 are warranted. 6. limitation studies published in chinese were not included in this study due to language strain. so, the language of studies had restricted the search and this study is limited by the small sample size. 7. declarations 7.1. acknowledgements none. 7.2. authors contributions salut muhidin: study design, data collection, writing draft of study. zahra behboodi moghadam: study design, data collection, writing draft of study. maryam vizheh: study design, data collection, writing draft of study, writing manuscript, supervision of study 7.3. funding support no fund was received for this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e49 7.4. conflict of interest the authors declared no conflicts of interest regarding authorship and publication of this article. references 1. singhal t. a review of coronavirus disease-2019 (covid-19). the indian journal of pediatrics. 2020:1-6. 2. fan c, lei d, fang c, li c, wang m, liu y, et al. perinatal transmission of covid-19 associated sars-cov-2: should we worry? clinical infectious diseases. 2020. 3. wang1a x, zhou2a z, zhang j, zhu f, tang y, shen x, et al. a case of 2019 novel coronavirus in a pregnant woman with preterm delivery. 2020. 4. rasmussen sa, jamieson dj, uyeki tm. effects of influenza on pregnant women and infants. american journal of obstetrics and gynecology. 2012;207(3):s3-s8. 5. https://www.nhlbi.nih.gov/health-topics/, studyquality-assessment-tools. 6. ma l-l, wang y-y, yang z-h, huang d, weng h, zeng xt. methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better? military medical research. 2020;7(1):1-11. 7. chen h, guo j, wang c, luo f, yu x, zhang w, et al. clinical characteristics and intrauterine vertical transmission potential of covid-19 infection in nine pregnant women: a retrospective review of medical records. the lancet. 2020;395(10226):809-15. 8. zhu h, wang l, fang c, peng s, zhang l, chang g, et al. clinical analysis of 10 neonates born to mothers with 2019-ncov pneumonia. translational pediatrics. 2020;9(1):51. 9. li n, han l, peng m, lv y, ouyang y, liu k, et al. maternal and neonatal outcomes of pregnant women with covid19 pneumonia: a case-control study. medrxiv. 2020. 10. liu y, chen h, tang k, guo y. clinical manifestations and outcome of sars-cov-2 infection during pregnancy. journal of infection. 2020. 11. chen r, zhang y, huang l, cheng b-h, xia z-y, meng q-t. safety and efficacy of different anesthetic regimens for parturients with covid-19 undergoing cesarean delivery: a case series of 17 patients. canadian journal of anesthesia/journal canadien d’anesthesie. 2020:1-9. 12. liu w, wang q, zhang q, chen l, chen j, zhang b, et al. coronavirus disease 2019 (covid-19) during pregnancy: a case series. 2020. 13. song l, xiao w, ling k, yao s, chen x. anesthetic management for emergent cesarean delivery in a parturient with recent diagnosis of coronavirus disease 2019 (covid-19): a case report. 14. yang j, zheng y, gou x, pu k, chen z, guo q, et al. prevalence of comorbidities in the novel wuhan coronavirus (covid-19) infection: a systematic review and meta-analysis. international journal of infectious diseases. 2020. 15. rasmussen sa, smulian jc, lednicky ja, wen ts, jamieson dj. coronavirus disease 2019 (covid-19) and pregnancy: what obstetricians need to know. american journal of obstetrics and gynecology. 2020. 16. liang h, acharya g. novel corona virus disease (covid19) in pregnancy: what clinical recommendations to follow? acta obstetricia et gynecologica scandinavica. 2020. 17. mardani m, pourkaveh b. a controversial debate: vertical transmission of covid-19 in pregnancy. kowsar. 18. favre g, pomar l, qi x, nielsen-saines k, musso d, baud d. guidelines for pregnant women with suspected sarscov-2 infection. the lancet infectious diseases. 2020. 19. lancet t. preliminary evidence suggests that new coronavirus cannot be passed from mother to child late in pregnancy. the lancet. (2020, mar 01). 20. jiao j. under the epidemic situation of covid-19, should special attention to pregnant women be given? journal of medical virology. 2020. 21. cui p, chen z, wang t, dai j, zhang j, ding t, et al. clinical features and sexual transmission potential of sars-cov2 infected female patients: a descriptive study in wuhan, china. medrxiv. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. muhidin et al. 10 table 3: summary of clinical, obstetric and neonatal characteristics of pregnant patients and their neonates author[ref ] number of samples chen et al. [7] 9 pregnant women liu et al.[10] 13 pregnant women zhu et al.[8] 10 neonates liu et al.[12] 3 pregnant women chen et al.[11] 17 pregnant women fan et al.[2] 2 pregnant women wang[3] 1 pregnant woman li et al.[9] 34 pregnant women (16 confirmed) song et al.[13] 1pregnant woman clinical characteristics age (y) 26–40 22 36 25-35 30 -34 29.1 (av*) 29, 34 28 26-37 30 exposure to infection, n (%) 9 (100%) 12 (92%) all (100%) 3 (100%) 3 (18%) 2(100%) 1 (100%) na 1 (100%) common symptoms at onset (n) fever (7) cough (4) fever (10) fatigue (10) dyspnea (3) fever (8) cough (4) fever(2) cough(2) fever (4) cough (4) chest distress (2) fever (2) fever fever (5) cough (1) fever, cough, myalgia severe pneumonia/ mechanical ventilation none 1(7%) none none none none 1(100%) none none maternal death none none none none none none none none none diagnosis qrt-pcr* qrt-pcr qrt-pcr qrt-pcr qrt-pcr qrt-pcr qrt-pcr qrt-pcr qrt-pcr main reported laboratory findings (n) lymphopenia (5) elevated crp* (6) increased alt&ast*(3) na na decreased albumin(all) thrombocytopenia (1) lymphopenia (5) elevated crp (7) lymphopenia (1) lymphopenia decreased albumin elevated crp lymphopenia (7) elevated crp(16) na abnormal radiologic findings (ggo) yes na yes yes yes yes yes yes yes treatment oxygen therapy(all) antiviral therapy (6) antibiotic therapy(all) na na oxygen therapy(all) antiviral therapy (all) antibiotic therapy(n=2) na antiviral therapy (all) antibiotic therapy (all) oxygen therapy antiviral therapy antibiotic therapy antibiotics (all) antiviral therapy (4) na prenatal characteristics gestational age 36 w39w,4d < 28w (n=2) 3rd trimester (n= 11) 3139 w 38w,4d40w <37 w (n=3) ≥37 w (n=14) 36 w5d & 37w 30w c#: 38±0.2w s#:38±2.8w 36w,3d prenatal comorbidities before the infection, (n) gestational htn*(1), preeclampsia (1), inïňćuenza(1) none vaginal bleeding (1) hypothyroid (1) gdm* (1) gestational htn(1), gdm* (2) anemia (5) vaginal bleeding (1) none htn, pco*, hbs* (3) gdm* (3) hypothyroidism (2), preeclampsia (1) sinus tachycardia(1) none complications, (n) fetal distress (2) prom*( 2) preterm labor (4) fetal distress (3) stillbirth(1) fetal distress (6) prom(3) abnormal cord (2) previa(1) abnormal af(2) mods*(1) fetal distress (1) na none none fetal distress (3) prom (1) placental abruption (1) none this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e49 table 3: summary of clinical, obstetric and neonatal characteristics of pregnant patients and their neonates mode of delivery(n) all c/s* all c/s c/s(7), nvd (2) c/s(2), nvd (1) all c/s (17) c/s(2) c/s c: c/s(14) s: c/s(16) c/s indication of c/s (n) covid 19/ fetal distress(2) preeclampsia (1) prom(2) history of c-section(1) history of stillbirth(1) covid 19/ fetal distress(3) stillbirth (1) prom(1) covid 19/ fetal distress (6) abnormal af (2), abnormal cord (2), previa (1) prom(3) covid 19 covid 19 covid 19/ persistent fever (1) covid 19/ mother’s admission to icu covid 19 covid 19/ history of c-section onset to delivery (days) 1-7 d (before delivery) na 1-6 d before (4)day of delivery (2) 1-3 d after delivery (3) 1-15 d before delivery na 7-11 d before delivery 6 d before delivery 2 d before (1) day of delivery(1) missing data of others 8 d before delivery preterm labor, n (%) 4 (44%) (>36w) 6, (46%) 3236 w 6 (46%) none 3(18%) 1(36w5d) 1(100%) c: 4 (23.5%) s: 4 (21.1%) 1(100%) assessment of vertical transmission breast milk af, umbilical cord blood, na na placenta tissue, vaginal mucus, breast milk, umbilical cord blood, serum, urine na maternal serum, vaginal swab, breast milk, umbilical cord blood, placenta tissue, af af, placenta, umbilical cord blood, gastric juice, stool samples na amniotic fluid, umbilical cord blood, breast milk, postpartum complication, n (%) postpartum fever 6 (67%) na none none e: hypotension, 12 (86%) none none postpartum fever, c: 8 (50.0%) s: 6 (33.3%) none neonates fetal weight(gram) 18803820 na 15203800 32503670 e*: 3,280 (330) g*: 2,780 (180) 2,890 &3400 1830 c:3078.2 ± 565.0 s: 3188.4 ± 520.5 3630 abnormal fetal weight lbw(2) 2(sga) 1(lga) none none none lbw lbw c: 3 (17.6%) s: 2 (10.5%) none apgar score, 1-5 min 8–9 & 9–10 10 & na 7–10 & 8–10 8&9 79& 9-10 9&10 9-10 9.6 ± 0.510.0 8-9 vertical transmission none none none none none none none none none special pediatric complication (n) none na one died shortness of breath (6) fever (2), tachycardia (1), gastrointestinal symptoms (4) death (1) chorioamnionitis(1) meconium stained amniotic fluid (1) none mild pneumonia(1) lymphopenia(2) low-grade fever(1) abdominal distension (1) na none none neonate’s sars-cov-2 all negative all negative all negative all negative all negative all negative all negative all negative all negative abbreviation: sars-cov-2=severe acute respiratory syndrome coronavirus 2; mv = mechanical ventilation prom=premature rupture of membrane; mods=multiple organ dysfunction syndrome; c-section=caesarean section, e: epidural anesthesia, g: general anesthesia, av: average; qrt-pcr: quantitative real-time reverse transcription-polymerase chain reaction; crp: c-reactive protein; alt: amino alanine transferase; ast: aspartate amino transferase; htn: hypertension; pco: polycystic ovary syndrome; hbs: hepatitis b; mods: multiple organ dysfunction syndrome; c/s: cesarean section # confirmed& suspected cases this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion conclusion limitation declarations references archives of academic emergency medicine. 2019; 7 (1): e8 or i g i n a l re s e a rc h comparing sensitivity of ultrasonography and plain chest radiography in detection of pneumonia; a diagnostic value study ebrahim karimi1∗ 1. emergency department, be’sat hospital, aja university of medical sciences, tehran, iran. received: october 2018; accepted: december 2018; published online: 22 january 2019 abstract: introduction: rapid detection of pneumonia and early initiation of antibiotic therapy are associated with better prognosis in patients. the present study was designed aiming to evaluate the sensitivity of chest ultrasonography performed by emergency medicine specialists in detection of pneumonia and comparing it with plain radiography. methods: in the present diagnostic accuracy study, patients presenting to the emergency department with clinical symptoms of lung infection underwent plain radiography, ultrasonography, and computed tomography (ct) scan of chest and the screening performance characteristics of plain radiography and ultrasonography were compared considering ct scan findings as the gold standard. results: 280 patients with the mean age of 56.47 ± 19.79 (10 – 92) years were studied (57.1% male). the results of chest ct scan were indicative of infection symptoms being present and confirmed pneumonia diagnosis for all the patients. out of the 280 cases of pneumonia confirmed via chest ct scan, 17 (6.1%) cases were not detected via ultrasonography and 48 (17.1%) cases were missed by chest radiography (false negative cases). no false positive case was reported by ultrasonography or chest x-ray. since all of the ct scans were positive, no comment can be made regarding the specificity of the evaluated tests, but sensitivity of ultrasonography and plain radiography were 93.92 (90.28 – 96.31) and 82.85 (77.81 – 86.97), respectively (p = 0.583). conclusion: based on the findings of the present study, although the sensitivity of ultrasonography in detection of pneumonia was significantly higher than chest x-ray, overall the screening performance characteristics of the 2 tests were not significantly different. therefore, considering characteristics such as safety, low cost, being portable, and being available, ultrasonography seems to be a reasonable tool for screening and diagnosis of patients with pneumonia. keywords: diagnostic imaging; ultrasonography; sensitivity and specificity; radiography, thoracic; tomography, x-ray computed cite this article as: karimi e. comparing sensitivity of ultrasonography and plain chest radiography in detection of pneumonia; a diagnostic value study. arch acad emerg med. 2019; 7(1): e8. 1. introduction pneumonia is a common cause of emergency department (ed) visits and has been reported to be responsible for 1 million hospitalizations annually (1). patients usually present with cough, tiredness, fever, shortness of breath, and pleuritic chest pain in typical cases. diagnosis of pneumonia is usually done in ed and if it is not detected it will be associated with a high risk of complications and mortality. rapid diagnosis of pneumonia and early treatment with antibiotic ∗corresponding author: ebrahim karimi; emergency department, be’sat hospital, afsariyeh avenue, basij highway, tehran iran. tel: +989124544838 email: ebrahimkarimi86@gmail.com are factors that have been associated with better prognosis and outcome (2, 3). history taking and clinical examination are the basis of diagnosing this disease and there are positive findings in history and clinical examination of these patients, including rales, rhonchi, wheezing, bronchial respiratory sounds, reduction of respiratory sounds, and dullness to percussion in chest (4). confirmation of diagnosis for this disease depends on imaging. sensitivity of plain chest radiography in detection of pneumonia has been reported as 38% to 76% in studies (5-8). although chest computed tomography (ct) scan is considered the standard in detection of pneumonia, it is associated with disadvantages such as unavailability and high exposure to radiation (9, 10). currently, chest ultrasonography is very popular for detection of pulmonary this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. karimi et al. 2 diseases such as pneumothorax, pulmonary edema, pleural effusion and pneumonia as a cheap, available, safe, and portable tool (11). sensitivity of ultrasonography compared to radiography has been reported to be between 80% and 90% in detection of pneumonia (8, 12, 13). with the introduction of emergency medicine discipline in iran, all the teaching wards have been provided with ultrasound devices and emergency medicine specialists have been trained for using this tool. therefore, the present study was designed aiming to evaluate the sensitivity of chest ultrasonography performed by emergency medicine specialists in detection of pneumonia and comparing it with plain radiography. 2. methods 2.1. study design and setting the present diagnostic accuracy study has been performed on patients presenting to the emergency department of be’sat hospital, tehran, iran, with symptoms of pulmonary infection in the time interval between october 2015 and march 2017. methodology of the present study was approved by the ethics committee of aja university of medical sciences and the researchers adhered to the ethical principles presented in helsinki declaration and keeping patient data confidential. all the probable costs inflicted on the patients were provided by the research team. 2.2. participants adult patients (over 18 years of age) presenting to the mentioned emergency department with clinical symptoms of pneumonia such as cough, phlegm, shortness of breath, hemoptysis, and temperature higher than 38◦c were studied using non-probability convenience sampling. pregnant patients, those with immunodeficiency, those consuming corticosteroids or any other immunosuppressant, those affected with chronic kidney or liver failure, and hemodynamically unstable patients were excluded from the study. no sex limitation was applied in the present study. 2.3. imaging after history taking, accurate clinical examination, evaluation of vital signs, dismissing cardiac causes for shortness of breath including heart attack, and providing primary healthcare, explanations regarding the aims of the study were given to the patients or their relatives. then chest ultrasonography was performed on participants by trained emergency medicine residents under supervision of the in charge attending emergency medicine specialist. all ultrasounds were performed with samsung hm70a device using a curved probe with 3.5 – 5 mhz frequency for observing the pulmonary and pleural parenchyma and 7.5 – 10 mhz frequency for observing more superficial lesions of the chest. for ultrasonographic examination of the lungs, each half of the chest was divided into anterior (from the parasternal line to the anterior auxiliary line), lateral (between the posterior and middle auxiliary lines), and posterior (from the posterior auxiliary line to the paravertebral line) sections and evaluated separately. the depth of ultrasound field in this study was adjusted between 16 and 18 centimeters. ultrasonographic symptoms evaluated in this study included air bronchogram, fluid bronchogram, pleural effusion, b lines (comet tail sign), and subpleural consolidation. after the performance of ultrasonography, patients were sent to the imaging unit to undergo plain radiography and chest ct scan. chest radiographies were performed in standing position from both anterior-posterior and lateral views for all the patients. helical ct scan was performed on patients without injection of a contrast agent. interpretation of the chest radiographies and ct scans was done by an emergency medicine specialist and a radiologist, separately, both of whom were blind to the clinical and ultrasonography findings of the patients. 2.4. data gathering an emergency medicine specialist was responsible for recording patients’ data. for this purpose, a checklist was filled out for each patient, which consisted of age, sex, chest ultrasound findings, plain chest radiography findings, and chest ct scan findings. 2.5. statistical analysis to analyze data, spss 20 statistical software was used. findings were reported using mean and standard deviation or frequency and percentage indices summarized in tables. to calculate screening performance characteristics of ultrasonography and plain chest x-ray, a medical calculator was used and sensitivity, specificity, positive and negative predictive values (ppv and npv ), and positive and negative likelihood ratios (plr and nlr) were reported with 95% confidence interval (ci). p values less than 0.05 were considered statistically significant. table 1: chest ultrasonography findings of studied patients signs frequency (%) air bronchogram 160(57.1) fluid bronchogram 118 (42.1) pleural effusion 143 (51.1) b lines (comet tail sign) 126 (45.0) subpleural consolidation 62 (22.1) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e8 table 2: screening performance characteristics of chest ultrasonography and radiography in diagnosis of pneumonia characteristics ultrasonography radiography sensitivity 93.92 (90.28-96.31) 82.85 (77.81-86.97) specificity nan nan ppv 100.00 (98.20100.00) 100.00 (97.96100.00) npv 0.00 (0.00-22.92) 0.00 (0.00-20.30) plr infinite infinite nlr infinite infinite nan: the calculation cannot be performed because the values entered include one or more instances of zero. ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio. 3. results 280 patients with the mean age of 56.47 ± 19.79 (10 – 92) years were studied (57.1% male). table 1 shows the chest ultrasonography findings of these patients. in 118 (42.1%) cases, positive ultrasonography findings were on the right, 96 (34.3%) were on the left, and 48 (17.1%) were bilateral. the results of chest ct scan were indicative of infection symptoms being present and pneumonia diagnosis was confirmed for all the patients. out of the 280 cases of pneumonia confirmed via chest ct scan, 17 (6.1%) cases were not detected via ultrasonography and 48 (17.1%) cases were missed by chest radiography (false negative cases). no false positive case was reported by ultrasonography or chest x-ray. table 2 depicts the screening performance characteristics of ultrasonography and plain chest radiography in detection of pneumonia considering chest ct scan as the gold standard. since all of the ct scans were positive, no comment can be made regarding the specificity of the evaluated tests, but as shown in table 2, sensitivity of ultrasonography in detection of pneumonia was higher than plain radiography, yet this difference was not clinically significant (p = 0.583). 4. discussion based on the findings of the present study, although the sensitivity of ultrasonography in detection of pneumonia was significantly higher than chest x-ray, overall the screening performance characteristics of the 2 tests were not significantly different. therefore, considering characteristics such as safety, low cost, being portable, and being available, ultrasonography seems to be a reasonable tool for screening and diagnosis of patients with pneumonia. using lung ultrasonography in evaluation of patients is becoming more popular in emergency department (14). although old methods are still used for diagnosis, lung ultrasonography can reduce the diagnostic errors of plain radiography as a helping tool. in addition, ultrasound is a useful device for follow-up of patients with pneumonia. decrease in air broncogram and the volume of pleural effusion compared to the primary ultrasounds can be considered signs of improvement in the patient (15). in children, due to the high risk of cancer in the early years of life in case of being exposed to radiation, ultrasonography can be a better method than ct scan and plain chest radiography for detection of pneumonia. in children, due to the small body size and small pulmonary mass, echo penetration is higher and a higher volume of the lung can be seen (15). by studying 144 adults, bourcier et al. reported 95% sensitivity for ultrasonography in detection of pneumonia and introduced it as the first line of diagnosis for these patients (5). in 2012, by studying 362 patients with suspected pneumonia acquired from the society, reissig et al. reported 93% sensitivity for detection of pneumonia and expressed that about 8% of the lesions related with pneumonia are not detectable via ultrasonography and negative results in ultrasonography are not enough for ruling out pneumonia (15). in a brief report, taghizadieh et al. reported the high accuracy of ultrasonography compared to plain chest radiography in detection of pneumonia (7). of course, ultrasonography is dependent on the individual performing it and emergency physicians need to be familiar with the ultrasonographic appearance of other differential diagnoses that can lead to consolidation such as lymphoma and bronchoalveolar carcinoma (16, 17). overall, like many other diagnostic methods, if ultrasonography is performed for a suitable person, in proper conditions and by a skillful person, it can play an important role in screening and detection of pneumonia, which lead to rapid initiation of treatment, improving the outcome of patients with pneumonia as a result. therefore, including ultrasonography training in detection of pneumonia in emergency resident’s course syllabus seems important more than ever. 5. limitation the present study was done on patients with suspected pneumonia in one center and this limits the generalization of its findings. on the other hand, the dependence of ultrasonography on the individual performing it should be considered in interpretation and generalization of the data. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. karimi et al. 4 6. conclusion based on the findings of the present study, although the sensitivity of ultrasonography in detection of pneumonia was significantly higher than chest x-ray, overall the screening performance characteristics of the 2 tests were not significantly different. therefore, considering characteristics such as safety, low cost, being portable, and being available, ultrasonography seems to be a reasonable tool for screening and diagnosis of patients with pneumonia. 7. appendix 7.1. acknowledgements all the emergency department staff members who cooperated throughout the study are thanked. 7.2. author contribution the author met the standard criteria for authorship based on the recommendations of the international committee of medical journal editors. authors’ orcids ebrahim karimi: 0000-0002-3542-9099 7.3. funding/support no fund has been received. 7.4. conflict of interest there is none. references 1. halm ea, teirstein as. management of communityacquired pneumonia. new england journal of medicine. 2002;347(25):2039-45. 2. gaieski df, mikkelsen me, band ra, pines jm, massone r, furia ff, et al. impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. critical care medicine. 2010;38(4):1045-53. 3. kumar a, zarychanski r, light b, parrillo j, maki d, simon d, et al. early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. critical care medicine. 2010;38(9):1773-85. 4. rosh aj, newman dh. evidence-based emergency medicine/rational clinical examination abstract. diagnosing pneumonia by medical history and physical examination. ann emerg med. 2005;46(5):465-7. 5. bourcier j-e, paquet j, seinger m, gallard e, redonnet jp, cheddadi f, et al. performance comparison of lung ultrasound and chest x-ray for the diagnosis of pneumonia in the ed. the american journal of emergency medicine. 2014;32(2):115-8. 6. self wh, courtney dm, mcnaughton cd, wunderink rg, kline ja. high discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ed patients: implications for diagnosing pneumonia. the american journal of emergency medicine. 2013;31(2):401-5. 7. taghizadieh a, ala a, rahmani f, nadi a. diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report. 2014. 2014;3(3):3. 8. cortellaro f, colombo s, coen d, duca pg. lung ultrasound is an accurate diagnostic tool for the diagnosis of pneumonia in the emergency department. emerg med j. 2012;29(1):19-23. 9. brenner dj, hall ej. computed tomography–an increasing source of radiation exposure. the new england journal of medicine. 2007;357(22):2277-84. 10. esayag y, nikitin i, bar-ziv j, cytter r, hadas-halpern i, zalut t, et al. diagnostic value of chest radiographs in bedridden patients suspected of having pneumonia. the american journal of medicine. 2010;123(1):88.e1-5. 11. yousefifard m, baikpour m, ghelichkhani p, asady h, shahsavari nia k, moghadas jafari a, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. 2016. 2016;4(1):10. 12. chavez ma, shams n, ellington le, naithani n, gilman rh, steinhoff mc, et al. lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. respiratory research. 2014;15(1):50. 13. caiulo va, gargani l, caiulo s, fisicaro a, moramarco f, latini g, et al. lung ultrasound characteristics of community-acquired pneumonia in hospitalized children. pediatric pulmonology. 2013;48(3):280-7. 14. karimi e, aminianfar m, zarafshani k, safaie a. the accuracy of emergency physicians in ultrasonographic screening of acute appendicitis; a cross sectional study. 2016. 2016;5(1). 15. reissig a, copetti r, mathis g, mempel c, schuler a, zechner p, et al. lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study. chest. 2012;142(4):965-72. 16. bedetti g, gargani l, corbisiero a, frassi f, poggianti e, mottola g. evaluation of ultrasound lung comets by hand-held echocardiography. cardiovascular ultrasound. 2006;4:34. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e8 17. shah s, noble ve, umulisa i, dushimiyimana jm, bukhman g, mukherjee j, et al. development of an ultrasound training curriculum in a limited resource international setting: successes and challenges of ultrasound training in rural rwanda. international journal of emergency medicine. 2008;1(3):193-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 77 emergency (2014); 2 (2): 77-80 original research comparison of intravenous ketamine with morphine in pain relief of long bones fractures: a double blind randomized clinical trial saeed majidinejad, mehrdad esmailian, mehrdad emadi* department of emergency medicine, isfahan university of medical sciences, isfahan, iran abstract introduction: the selective medication for pain control in many clinical situations is morphine but its complications prevent its widespread use. ketamine has been introduced as an alternative for morphine in some studies. however, the efficacy of its solitary use has not yet been evaluated. therefore, the present study was undertaken to evaluate the effect of ketamine alone in relieving pain in trauma patients referring to an emergency unit. methods: in this double-blind clinical trial, patients with long bone fractures were randomly divided into two groups of treatment with intravenous (iv) morphine at a dose of 0.1 mg/kg and treatment with iv ketamine at a dose of 0.5 mg/kg. pain severity of the patients was recorded before and 10 minutes after injection based on numeric rating scale. the means in the two groups were compared using independent t-test. then the kaplan-meier curve and log rank analysis were used to evaluate the success of treatment. results: 126 patients were included in this study. the mean ages of the patients in the morphine and ketamine groups were 33.6±14.3 and 35.1±13.5 years, respectively (p=0.54). after therapeutic intervention, the pain severity significantly decreased in ketamine (2.7±1.8; p<0.0001) and morphine (2.4±1.5; p<0.0001) groups, with a similar effect of both medications on alleviating pain (p=0.28). the success rate of the treatment at 10-minute interval in groups receiving ketamine and morphine were 59 (93.65%) and 61 (96.8%) patients, respectively (p=0.62). conclusion: the results of the present study showed that administration of ketamine at a low dose (0.5 mg/kg) results in a significant decrease in the severity of acute pain in patients with fractures of long bones. this palliative effect is very similar to that of morphine. key words: bone fracture; pain management; analgesia; ketamine; morphine cite this article as: majidinejad s, esmailian m, emadi m. comparison of intravenous ketamine with morphine in pain relief of long bones fractures: a double-blind randomized clinical trial. emergency. 2014;2(2):77-80. introduction:1 ractures have a high incidence rate in traffic accidents and are one of the three most important complications during accidents (1). each year millions of people all over the world suffer from bone fractures, the complications of which threaten the patients’ health for several years (2, 3). one of the most important measures in the management of such patients in the emergency unit is fixation and pain control. opioids are one of the main and most effective medications to relieve pain (4, 5) by suppression of pain center in the cns through stimulation of µ and δ receptors. however, complications such as dependence, tolerance, suppression of respiratory center and activation of vomiting center are some of their problems (6). other medications are nsaids, which prevent synthesis of *corresponding author: mehrdad emadi; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989133275409; fax:+983116685555 email: emadimehrdad66@yahoo.com received: 13 march 2014; accepted: 16 may 2014 prostaglandin e2 by inhibiting cycloxygenase. nonetheless, this group of medications has gastrointestinal complications and even some of them exhibit renal and hepatic toxicity (7). paracetamol, aminophylline, tramadol, nefopam etc are some other drugs that have been evaluated in different studies for pain relief. apart from these medications, ketamine is another medication, which has been introduced. it is one of the medications, which is used for general anesthesia and sedation. ketamine is an antagonist of n-methyl-d-aspartate (nmda) (8, 9) and is used in iv, intramuscular, enteric, subcutaneous, intra-nasal, rectal and epidural forms. however, at higher doses it can have complications such as hallucination, dysphoria, nightmares, an increase in intracranial pressure, hypertension, tachycardia, tremors and clonic-tonic seizures (10, 11). several studies have shown that ketamine is effective in pain relief; however, in the majority of studies available, ketamine has been used in conjunction with other analgesics and no study is available in which use of this medication alone has been comprehensively evaluated for f this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidinejad et al 78 pain relief. on the other hand, studies available have not evaluated the use of this medication in trauma patients in emergency units. therefore, the present study was designed to evaluate the effect of ketamine alone on pain relief in trauma patients referring to an emergency unit of a third-level hospital. methods: study design and setting the present double-blind clinical trial was carried out in 2012-2013 in al-zahra and ayatollah kashani educational centers in isfahan, iran. the subjects consisted of patients with fractures of long bones, referring to the emergency unit. the patients were included in the study consecutively. the protocol of the study was approved by the ethics committee of isfahan university of medical sciences. the helsinki research protocol was observed during the whole study period. the study was registered in iranian registry of clinical trial (irct number: irct2015042812072n3). subject the inclusion criteria consisted of an age range of 18-55 years, fractures of long bones and consent to participate in the study. exclusion criteria consisted of drug abuse, trauma to the head, symptoms and signs of increased intracranial pressure, a decrease in consciousness level, respiratory problems, a history of asthma, contraindications for ketamine (i.e. a history of cardiac problems, especially congestive heart failure, ischemic cardiac conditions, hypertension and patients with cerebrovascular attack) and morphine (i.e. asthma, respiratory problems, hemodynamic instability). in addition, in case of any allergic reaction to any of the medications used, the patient was excluded from the study. the sample size was estimated at 63 subjects in each group based on numeric rating scale (nrs) at 95% confidence interval, a study power of 80%, a standard deviation of 1.6 for pain severity and a minimum difference significance of 2 between the two groups (12). intervention first the patients’ demographic and clinical data were recorded, which consisted of background diseases, drugs taken, drug abuse, drug allergies, the last meal eaten, location of fracture and severity of pain. then the eligible patients were randomly divided into two groups: the group receiving iv morphine at a dose of 0.1 mg/kg and the group receiving iv ketamine at a dose of 0.5 mg/kg. to make sure of the double-blind protocol of the study, preparation of the solutions, injections and registration of the results were carried out by three different physicians who had no contact or relationship with each other. the data on the injection of medications were available only to the chief researcher and the medical care personnel were granted access to such data only when drug complications arose. in such a case, the patient in question was excluded from the study. the severity of pain was registered before injection and 10 minutes after injection based on nrs (13). in cases in which pain did not subside after 10 minutes (a decrease in pain severity equal to or less than 3), the patient received half the initial dose again. finally, drug side effects in patients were evaluated and recorded. statistical analysis data were entered into spss 11.5 and were analyzed after being transferred to stata 11.0 software. the severity of pain before administration of medications and 10 minutes after initiation of treatment, was reported as means ± standard deviations and analyzed using independent t-test. then kaplan-meier curves and log rank analysis were used to evaluate the success of treatment, which was defined as a decrease of 3 scores in pain severity. statistical significance was set at p<0.05 in all the analyses. results: 126 patients were included in the study and randomly divided into two equal groups of morphine and ketamine. the mean ages of the patients in the morphine and ketamine groups were 53.6±14.3 and 35.1±13.5 years, respectively (p=0.54). forty-five (71.4%) and 51 (80.95%) patients were male in the ketamine and morphine groups, respectively (p=0.21). table1 shows the site of fractures. the mean pain severity scores at admission in the ketamine and morphine groups were 8.8±0.8 and 8.95±0.8, respectively (p=0.32). after therapeutic intervention, the severity of pain decreed significantly in the ketamine (2.7±1.8; p<0.001) and morphine groups (2.4±1.5; p<0.001), with no significant differences between the two groups (p=0.28), indicating that both medications are equally effective in alleviating pain (figure 1). kaplan-meier curve showed that five minutes after initiation of injection, ketamine and morphine resulted in a successful decrease in pain severity in 33 (52.4%) and 38 (60.3%) patients, respectively. this rate increased to 59 (93.65%) and 61 (96.8%) patients, respectively, after 10 minutes. log rank test did not show any significant difference in success rates between the two groups (p=0.62) (figure 2). none of the patients receiving morphine exhibited any complications; however, during the intervention, six patients (9.5%) receiving ketamine developed emertable1: demographic variables (%) of patients  variable ketamine morphine p gender male 45 (71.4) 51 (81.0) 0.2 female 18 (28.6) 12 (19.0) site of fracture upper extremities 23(37.1) 30 (48.4) 0.2 lower extremities 39 (62.9) 32 (51.6) baseline pain score 8.8±0.8 8.95±0.8 0.32 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 79 emergency (2014); 2 (2): 77-80 gence phenomenon (p=0.28). and four patients (6.3%) in this group required a rescue dose due to the short period of the drug effect (p=0.12). discussion: the results of the present study showed that administration of a low dose of ketamine (0.5 mg/kg) results in a significant decrease in pain severity of long bone fractures. this analgesic effect is very similar to that of morphine. the incidence of drug complications was higher in the ketamine group compared to the morphine group (p=0.028), with emergence phenomenon in four subjects. although the incidence of this complication was higher in the ketamine group, other studies have emphasized that since ketamine is one of the safest and most appropriate medications for sedation in emergency wards, such a complication should not preclude its use because this complication is resolved spontaneously without any therapeutic intervention (14). the majority of studies available have evaluated the efficacy of combination treatment with morphine/ ketamine in decreasing pain due to fractures. galinski et al showed that use of low doses of ketamine decreases the need for morphine up to 26% and its efficacy when administered alone is similar to that of morphine in alleviating pain (5). weinbroum et al evaluated the simultaneous administration of morphine/ketamine compared with morphine alone in decreasing pain severity after surgery and showed that simultaneous administration of morphine and ketamine results in a significant decrease in pain severity perception by patients (15). a systematic review, too, showed that use of ketamine as a supplementary medication results in a decrease in the need for morphine, preventing unfavorable complications (16). mccarty et al, too, reported that ketamine is an appropriate, rapid and safe sedative agent, which facilitates reduction of fractures in children in the emergency unit. however, they claim that ketamine should only be administered in locations, such as emergency units, where precise monitoring of patients is possible and an experienced physician is available in the center for the management of airways (17). snijdelaar et al reported that the combination of ketamine/morphine significantly decreases the need for morphine and has better analgesic effects (18). jennings et al reported similar findings but emphasized that more minor complications are seen with a combination of morphine/ketamine (12). one of the most important limitations of the present study was a short follow-up period of patients. in the present study, all the patients were evaluated for only 10 minutes, which precluded evaluation of the effect of ketamine at longer periods. therefore, it is suggested that in future studies the efficacy of the medication be evaluated at longer follow-up periods. another shortcoming of the present study was the absence of a placebo group. due to ethical considerations, it was not possible to follow the patients without any medicinal intervention and use only placebo. it was shown in the present study that iv administration of ketamine results in pain relief in bone fracture patients. however, the effect of this medication on the recurrence of pain is still unknown. therefore, it is possible that further administration of the medication will prevent recurrence of pain. in addition, the efficacy of other routes for administration of the medication, such as intramuscular, intranasal and local use, should be evaluated in future studies. in addition, use of different administration regimens, such the continuous use or infusion, should be evaluated in future studies. conclusion: the results of the present study showed that admin figure 1: means (sd) of pain severity in patients receiving ketamine and morphine before and after intervention. * indicates significant difference from the period before intervention at p<0.001. nrs: numeric rating scale.  0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 63 63 25 8 2 2morphine 63 63 30 11 4 4ketamine number of failure 0 10 151 2 3 4 5 6 7 8 9 11 12 13 14 time (minute) ketamine morphine kaplan-meier failure estimates figure 2: the treatment success rate in the morphine and ketamine groups at different time intervals.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com majidinejad et al 80 istration of a low dose of ketamine (0.5 mg/kg) results in a significant decrease in the severity of acute pain in patients with fractures of long bones. this analgesic effect is very similar to that of morphine. acknowledgments: the authors appreciate the insightful cooperation of medical sciences and the staffs of the emergency department of al-zahra hospital, isfahan, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. cameron m. world report on road traffic injury prevention. inj prev. 2004;10(4):255-6. 2. griffin xl, smith n, parsons n, costa ml. ultrasound and shockwave therapy for acute fractures in adults. cochrane database syst rev. 2012;2:cd008579. pubmed pmid: 22336847. 3. woolf ad, erwin j, march l. the need to address the burden of musculoskeletal conditions. best pract res clin rheumatol. 2012;26(2):183-224. 4. esmailian m, keshavarz m. synergistic effects of citalopram and morphine in the renal colic pain relief; a randomized clinical trial. emergency. 2014;1(2):26-9. 5. galinski m, dolveck f, combes x, et al. management of severe acute pain in emergency settings: ketamine reduces morphine consumption. am j emerg med. 2007;25(4):385-90. 6. campbell w. guide to prescribing in today's management of severe pain. prescriber. 2012;23(17):25-40. 7. tadros nn, bland l, legg e, olyaei a, conlin mj. a single dose of a non‐steroidal anti‐inflammatory drug (nsaid) prevents severe pain after ureteric stent removal: a prospective, randomised, double‐blind, placebo‐controlled trial. bju int. 2013;111(1):101-5. 8. panzer o, moitra v, sladen rn. pharmacology of sedativeanalgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. anesthesiology clinics. 2011;29(4):587-605. 9. roth bl, gibbons s, arunotayanun w, et al. the ketamine analogue methoxetamine and 3-and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate nmda receptor. plos one. 2013;8(3):e59334. 10. klepstad p, maurset a, moberg er, øye i. evidence of a role for nmda receptors in pain perception. eur j pharmacol. 1990;187(3):513-8. 11. sadove ms, shulman m, hatano s, fevold n. analgesic effects of ketamine administered in subdissociative doses. anesth analg. 1971;50(3):452-7. 12. jennings pa, cameron p, bernard s, et al. morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. ann emerg med. 2012;59(6):497-503. 13. holdgate a, asha s, craig j, thompson j. comparison of a verbal numeric rating scale with the visual analogue scale for the measurement of acute pain. emerg med. 2003;15(5‐6): 441-6. 14. treston g, bell a, cardwell r, fincher g, chand d, cashion g. what is the nature of the emergence phenomenon when using intravenous or intramuscular ketamine for paediatric procedural sedation? emerg med australas. 2009;21(4):31522. 15. weinbroum aa. a single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain. anesth analg. 2003;96(3):789-95. 16. subramaniam k, subramaniam b, steinbrook ra. ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. anesth analg. 2004;99(2):48295. 17. mccarty ec, mencio ga, walker la, green ne. ketamine sedation for the reduction of children's fractures in the emergency department. j bone joint surg. 2000;82(7):912. 18. snijdelaar dg, cornelisse hb, schmid rl, katz j. a randomised, controlled study of peri-operative low dose s(+)ketamine in combination with postoperative patientcontrolled s(+)-ketamine and morphine after radical prostatectomy. anaesthesia. 2004;59(3):222-8. archives of academic emergency medicine. 2020; 8(1): e69 or i g i n a l re s e a rc h prognostic factors of outcome in methanol poisoning; an 8-year retrospective cross-sectional study vahid yousefinejad1, badia moradi2∗, anvar mohammadi baneh3, farshad sheikhesmaeili1, asrin babahajian1 † 1. liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 2. student research committee, kurdistan university of medical sciences, sanandaj, iran. 3. internal medicine department, faculty of medicine, kurdistan university of medical sciences, sanandaj, iran. received: august 2020; accepted: september 2020; published online: 5 september 2020 abstract: introduction: identification of high-risk patients with poor prognosis is essential for quick diagnosis and treatment of methanol poisoning to prevent death and improve the outcome. the aim of this study was to evaluate the clinical and laboratory factors in patients with methanol poisoning to determine the prognosis and outcome. methods: in this retrospective cross-sectional study, all patients with methanol poisoning, who had presented to the emergency department of tohid hospital, sanandaj, iran from 2011 to 2019 (8 years) were enrolled using census method. multivariate logistic regression analysis was performed to find the independent predictive factors of poor outcome in the mentioned patients. results: methanol poisoning was diagnosed in 52 (11.55%) of the 450 cases admitted to hospital for alcohol intoxication. in multivariate analysis, time interval from methanol intake to hospital admission (or=1.06; 95% ci= 1.00-1.11; p=0.04), respiratory arrest (or=25.59; 95% ci= 1.37478.13; p=0.03), and higher concentration of blood glucose (or=1.03; 95% ci= 1.00-1.09; p=0.03) had a significant correlation with poor outcomes. conclusion: based on the findings of this study, delayed admission to hospital, respiratory arrest and hyperglycemia were identified as independent risk factors of poor outcome in methanol poisoning. keywords: poisoning; methanol; prognosis; outcome assessment, health care cite this article as: yousefinejad v, moradi b, mohammadi baneh a, sheikhesmaeili f, babahajian a. prognostic factors of outcome in methanol poisoning; an 8-year retrospective cross-sectional study. arch acad emerg med. 2020; 8(1): e69. 1. introduction methanol poisoning due to drinking illicit and homemade alcoholic beverages is a major medical problem worldwide (13) and despite advances in diagnosis and treatment, mortality rate in such patients is high (4) . if treatment is delayed or inadequate, mortality rate may reach up to 40%, and even if the patients survive, poisoning may lead to permanent blindness and long-term effects on their central nervous system (5-7). the symptoms of methanol poisoning appear 12 to 24 hours ∗corresponding author: badia moradi; student research committee, kurdistan university of medical sciences, sanandaj, iran. email: moradibadia@gmail.com. † corresponding author: asrin babahajian; liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. tel: +98-87-33247855, email: babahajian3@yahoo.com. after its intake, because its toxic effects are due to toxic metabolites of methanol and not methanol itself. moreover, in case of delayed hospitalization and treatment, severe metabolic acidosis occurs due to transformation of methanol to toxic metabolites (8). on the other hand, clinical symptoms (abdominal pain, shortness of breath/hyperventilation and visual disturbances) may mimic the signs and symptoms of other diseases. in fact, many patients die before reaching the hospital and being diagnosed with methanol poisoning (1, 2, 9). under iranian law, the sale, purchase and intake of alcoholic drinks are illegal and punishable. as a result, people who want to drink alcohol use industrial or homemade alcohol, which is sometimes a mixture of methanol and ethanol (10, 11). on the other hand, some people use alcohol containing methanol due to prohibition of the sale of alcoholic beverages or they are accidentally poisoned by this type of alcohol; however, they do not seek medical treatment due to social this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. yousefinejad et al. 2 shame and fear of legal punishment. methanol poisoning is increasing in recent years due to counterfeit alcohol intake, and fear of legal punishment and delay in the onset of the poisoning symptoms may delay patients’ referral to the hospital and thereby increase their mortality rate. whereas, rapid diagnosis and treatment are necessary to prevent death and to minimize neurological complications. therefore, researchers around the world are looking for methods to quickly identify high-risk patients with poor prognosis. in previous studies, factors such as delayed hospitalization after alcohol consumption, coma or seizures on admission, severe metabolic acidosis, and inadequate hyperventilation have been identified as indicators of poor prognosis in methanol poisoning (11-13). in iran, there have been few studies on clinical and epidemiological findings in groups of people who had experienced methanol poisoning, most of which were performed on small groups and paid little attention to para-clinical parameters (10, 11). this study investigated the clinical factors and para-clinical findings to determine the prognosis of methanol poisoning in patients who referred to tohid hospital, sanandaj, iran, over eight years (2011-2018). 2. methods 2.1. study design and setting in this retrospective cross-sectional study, patients with methanol intoxication presenting to emergency department of tohid hospital, sanandaj, iran, from 2011 to 2019 (8 years) were studied. the protocol of this study was approved by the ethics committee of kurdistan university of medical sciences (ir.muk.rec.1397/331) and the principles of confidentiality of information were respected by the researchers according to the helsinki declaration. 2.2. participants the medical records of patients presenting with alcohol intoxication were reviewed and those who had been treated with a diagnosis of methanol poisoning (based on clinical symptoms) were enrolled using census method and patients were excluded from the study if they had died before being evaluated. 2.3. data gathering data collection was done using a checklist containing information regarding demographic data (age, sex); clinical data including concomitant use of opioids or psychoactive drugs, suicide attempt, time interval between methanol intake and hospital admission, level of consciousness, visual disturbances, number of hemodialysis sessions, ventilation and administration of antidote (ethanol) in patients and laboratory findings including ph, pco2, osmolality gap, hco3, creatinine (cr), potassium (k) and blood sugar (bs). data collection was performed by an internal medicine resident. data were extracted from medical records of admitted patients. 2.4. outcome to evaluate outcomes, patients were divided into two groups: poor outcome (survivors with sequelae and those who died) and good outcome (survivors without sequelae). 2.5. statistical analysis spss software version 20 was used for data management and analysis. quantitative variables were reported as mean ± standard deviation (sd), and median and interquartile range (iqr) for data with normal and abnormal distribution, respectively. qualitative variables were presented as frequency (percentage). in addition, mann-whitney u test, t-test, and chi-square test were used to evaluate data with abnormal distribution, assess data with normal distribution, and compare categorical variables, respectively. a multivariate logistic regression model was applied to find the factors related to the outcome. p-values less than 0.05 were considered statistically significant. 3. results 3.1. demographic and clinical characteristics of patients of the 450 cases admitted to the emergency department of tohid hospital in sanandaj, iran, due to alcohol intoxication during the 8-year period, 52 (11.55%) were diagnosed with methanol intoxication. all of the patients were male; with the mean age of 32.78± 12.30 years (range 14-60 years). according to the medical records, 4 (7.7%) patients had attempted suicide by using alcohol (containing methanol), one of which died. concomitant use of opioids or psychoactive drugs was reported in 9 (17.3%) cases. the median time interval between methanol intake and hospital admission was 24 hours (range: 4 to 48 hours). on admission to the emergency department, 32 (61.5%) had visual disturbances. the patients’ consciousness state was evaluated and 32 (61.5%) were awake, 17 (32.7%) were comatose (gcs less than 8), and 3 (5.8%) were awake-coma (lost their consciousness after hospitalization). 10 (19.2%) patients needed ventilation due to respiratory arrest. hemodialysis was performed in all patients. the median time interval between hospital admission and beginning of hemodialysis was 2 hours, with the range of 1-3 hours. 14 patients (26.9%) underwent hemodialysis more than once. 13 (25%) patients were treated with ethanol as an antidote. a total of 12 (23.1%) patients were admitted to intensive care unit (icu). finally, death occurred in 8 (15.4%) patients, 4 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e69 table 1: demographic and clinical characteristics associated with poor outcome in patients with methanol poisoning variables outcome p-value good n=40 poor n=12 age (year) median (iqr) 29.5 (23.0 – 38.8) 37.5 (25.3 – 49.3) 0.14† location urban 35(87.5) 12(100.0) rural 5(12.5) 0(0.0) 0.58 intake to admission (hour) median (iqr) 18.0 (3.0 – 48.0) 48.0 (26.0 – 72.0) < 0.01† admission to hemodialysis (hour) median (iqr) 2.0 (1.0 – 3.0) 2.0 (0.6 – 3.8) 0.98† suicide yes 3 (7.5) 1 (8.3) no 37 (92.5) 11 (91.7) > 0.99§ coma on admission yes 11 (27.5) 6 (50.0) no 29 (72.5) 6 (50.0) 0.17§ visual symptoms on admission yes 24 (60.0) 8 (66.7) no 16 (40.0) 4 (33.3) 0.74§ frequency of hemodialysis once 32 (80.0) 6 (50.0) more than once 8 (20.0) 6 (50.0) 0.06§ antidote (ethanol) yes 9 (22.5) 4 (33.3) no 31 (77.5) 8 (66.7) 0.46§ respiratory arrest on admission yes 3 (7.5) 7 (58.3) no 37 (92.5) 5 (41.7) < 0.001§ continuous variables presented as median (interquartile range; iqr) and categorical variables are presented as frequency (%). † mann-whitney u test was used for analysis. § fisher’s exact test was used for analysis. table 2: laboratory factors associated with poor outcome in patients with methanol poisoning variables outcome p value good (n =40) poor (n =12) ph 7.28 (7.11 – 7.30) 7.10 (6.90 – 7.30) 0.09† † hco3 (mmol/l) 13.00 (7.90 – 19.55) 7.30 (5.92 – 16.42) 0.06 † † pco2 (kpa) 30.43 ± 10.66 28.01 ± (8.08) 0.50† osmolality gap 295.41± 8.94 299.14 ± 14.50 0.30† bs (mg/dl) 116.0 (104.0 – 136.0) 163.0 (156.0 – 323.0) < 0.001† † k (mmol/l) 4.07 ± 0.82 4.83 ± 0.89 0.01† cr (mol/l) 1.08 ± 0.32 1.41 ± 0.49 < 0.01† * continuous variables presented as mean ± standard deviation (sd) for normally distributed variables or median (interquartile range; iqr) for data that are not normally distributed. bs: blood sugar; k: potassium; cr: creatinine. † one-way anova was used for analysis. † † kruskal-wallis was used for analysis. (7.7%) survivors had ocular and cerebral sequelae, and other patients (76.9%) were discharged with complete recovery. 3.2. factors associated with poor outcomes details of demographic and clinical factors associated with poor outcome are shown in table1. the median time interval between methanol intake and hospital admission was higher in patients with poor outcome (48 hours, iqr: 26-72 hours) compared to those who recovered (18 hours, iqr; 3-48) (p< 0.01). respiratory arrest rate on admission was also significantly higher in poor outcome group; only 3 (30%) patients who had respiratory arrest on arrival survived without sequethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. yousefinejad et al. 4 table 3: the results of multivariate logistic regression analysis on the factors associated with a poor outcome in patients with methanol poisoning variables or 95% cip-value respiratory arrest 25.59 1.37 478.13 0.03 intake to hospital admission 1.06 1.00 1.11 0.04 high blood glucose level 1.03 1.00 1.09 0.03 or: odds ratio; ci: confidence interval. lae (p < 0.001). table 2 shows the laboratory findings. the concentrations of glucose (p<0.001), creatinine (p<0.01) and potassium (p=0.01) were higher in the poor outcome group. in contrast, ph (p= 0.09), pco2 (p= 0.50), hco3 (p= 0.06), and osmolality gap (p= 0.30) did not have a significant association with poor outcome. additionally, in multiple logistic regression analysis, increased time interval between intake and admission (or = 1.06; 95% ci: 1.00 to 1.11; p = 0.04), respiratory arrest (or = 25.59; 95% ci: 1.37 to 478.13; p = 0.03), and higher blood sugar level (or = 1.03; 95% ci: 1.00 to 1.09; p = 0.03) remained independently associated with poor outcome (table 3). 4. discussion in this study, clinical and para-clinical factors affecting the prognosis of methanol poisoning were investigated. the main findings indicated that methanol poisoning was diagnosed in only 11.55% of those admitted to tohid hospital in sanandaj, iran, due to alcohol poisoning over 8 years. delay in transfer to hospital, respiratory arrest on admission, and hyperglycemia were associated with poor prognosis (death and sequelae). in previous studies, respiratory arrest (1, 2, 11, 14) as well as more than 24 hours passing from methanol intake at the time of hospital admission (11) had been identified as factors predicting poor prognosis for methanol poisoning, which is consistent with our study. moreover, patients were asymptomatic 12 to 24 hours after methanol intake and this period was defined as the latent period. this latent period was most likely related to the period when methanol was metabolized to formaldehyde and formic acid (15). in an eight-year study, yaycäś et al. reported delayed hospitalization to be the cause of methanol poisoning deaths in 77.5% of patients (16) . najari et al., in their study, pointed to the causes of delay in initiation of treatment, which leads to long-term complications and mortality in patients, and cited difficult diagnosis of intoxication due to non-specific signs and symptoms, delay in patient’s referral, and the impossibility of obtaining a proper history of the patient (17). in the present study, the median time interval between methanol intake and hospital admission in patients with poor prognosis (morbidity and mortality) was greater than those who completely recovered. our study also showed that elevated serum levels of bs was associated with poor prognosis. in a retrospective study, sanaei-zadeh et al. examined 95 people who had been treated for methanol poisoning at loghman and hazrat rasoul hospitals between 2003 and 2010 in tehran, iran. they reported that blood serum glucose levels in those who died (219±99 mg/dl) was significantly higher than those who survived (140±55 mg/dl) (p <0.001) and reported that among the factors studied, serum glucose levels above 140 were a risk factor in predicting mortality in these patients (14). the mechanism of hyperglycemia in methanol poisoning is unclear. methanol poisoning has been reported to be associated with acute pancreatitis (18, 19), which can play a role in hyperglycemia. another mechanism that may lead to an increase in blood glucose levels in methanol poisoning is stress-induced hyperglycemia, which is commonly seen in critically ill patients. in other words, increased levels of acute stress hormones may play a role in development of methanol poisoning. therefore, insulin therapy and blood sugar control may be applied in the management of methanol poisoning (20, 21). in the present study, all the subjects were male, which indicates that methanol abuse in our country occurs predominantly in men. in the study of hassanian et al., 23 of the 25 cases of methanol poisoning were male (11) . other studies have shown that men are more likely to be poisoned with methanol and die from it. in these studies, the higher prevalence of alcohol consumption in men compared to women was reported as the reason for the higher prevalence of methanol poisoning in men (22, 23). in addition, ocular symptoms were reported as one of the major symptoms of methanol poisoning associated with retinal toxicity, which ranged from blurred vision, changes in visual field, photophobia, difficulty in adjusting light and double vision to complete blindness and nystagmus, which was uncommon. in this study, 61% of patients had visual impairment on admission and findings from other studies also reported visual impairments in 29–77% of all patients (1, 24, 25). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e69 5. limitations limitations of this study included small sample size, the retrospective nature of the study, and the short-term followup. in addition, due to the lack of measurement of serum methanol levels in patients, diagnosis was based on clinical findings in patients. 6. conclusion based on the findings of this study, delayed admission to hospital, respiratory arrest, and hyperglycemia were identified as independent risk factors of poor outcome in methanol poisoning. 7. declarations 7.1. acknowledgements this article is part of dr. badia moradi’s thesis, who was an internal medicine resident at the time of the study. the authors would like to convey their full appreciation to vice chancellor for research, kurdistan university of medical sciences for their financial support. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids vahid yousefinejad: 0000-0002-9928-938x badia moradi: 0000-0002-1924-553x anvar mohammadi baneh: 0000-0002-0717-5474 farshad sheikhesmaeili: 0000-0003-2067-5032 asrin babahajian: 0000-0003-0278-1560 7.3. funding/support this study was supported by kurdistan university of medical sciences (grant number: ir.muk.rec.1397/331). 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. hovda ke, hunderi oh, tafjord ab, dunlop o, rudberg n, jacobsen d. methanol outbreak in norway 2002– 2004: epidemiology, clinical features and prognostic signs. journal of internal medicine. 2005;258(2):181-90. 2. paasma r, hovda ke, tikkerberi a, jacobsen d. methanol mass poisoning in estonia: outbreak in 154 patients. clinical toxicology. 2007;45(2):152-7. 3. zakharov s, pelclova d, urban p, navratil t, diblik p, kuthan p, et al. czech mass methanol outbreak 2012: epidemiology, challenges and clinical features. clinical toxicology. 2014;52(10):1013-24. 4. megarbane b, borron sw, baud fj. current recommendations for treatment of severe toxic alcohol poisonings. intensive care medicine. 2005;31(2):189-95. 5. roberts dm, yates c, megarbane b, winchester jf, maclaren r, gosselin s, et al. recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. critical care medicine. 2015;43(2):461-72. 6. vaneckova m, zakharov s, klempir j, ruzicka e, bezdicek o, liskova i, et al. methanol intoxication on magnetic resonance imaging-case reports. ceska a slovenska neurologie a neurochirurgie. 2014;77(2):235-9. 7. bezdicek o, klempir j, liskova i, michalec j, vaneckova m, seidl z, et al. sequelae of methanol poisoning for cognition. ceska a slovenska neurologie a neurochirurgie. 2014;77(3):320-5. 8. poisoning aaoctahcottgfm, barceloux dg, randall bond g, krenzelok ep, cooper h, allister vale j. american academy of clinical toxicology practice guidelines on the treatment of methanol poisoning. journal of toxicology: clinical toxicology. 2002;40(4):415-46. 9. levy p, hexdall a, gordon p, boeriu c, heller m, nelson l. methanol contamination of romanian homedistilled alcohol. journal of toxicology: clinical toxicology. 2003;41(1):23-8. 10. massoumi g, saberi k, eizadi-mood n, shamsi m, alavi m, morteza a. methanol poisoning in iran, from 2000 to 2009. drug and chemical toxicology. 2012;35(3):330-3. 11. hassanian-moghaddam h, pajoumand a, dadgar s, shadnia s. prognostic factors in methanol poisoning. human & experimental toxicology. 2007;26(7):583-6. 12. paasma r, hovda ke, hassanian-moghaddam h, brahmi n, afshari r, sandvik l, et al. risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes–a multicenter study. clinical toxicology. 2012;50(9):823-31. 13. shadnia s, rahimi m, soltaninejad k, nilli a. role of clinical and paraclinical manifestations of methanol poisoning in outcome prediction. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2013;18(10):865. 14. sanaei-zadeh h, esfeh sk, zamani n, jamshidi f, shadnia s. hyperglycemia is a strong prognostic factor of lethality in methanol poisoning. journal of medical toxicology. 2011;7(3):189-94. 15. pooladanda v, thatikonda s, godugu c. the current understanding and potential therapeutic options to combat covid-19. life sciences. 2020:117765. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem v. yousefinejad et al. 6 16. ayci n, agritmis h, turla a, koc s. fatalities due to methyl alcohol intoxication in turkey: an 8-year study. forensic science international. 2003;131(1):36-41. 17. najari f, baradaran i, najari d. methanol poisoning and its treatment. international journal of medical toxicology and forensic medicine. 2020;10(1):26639. 18. hantson p, mahieu p. pancreatic injury following acute methanol poisoning. journal of toxicology: clinical toxicology. 2000;38(3):297-303. 19. working party of the british society of g, association of surgeons of great b, ireland, pancreatic society of great b, ireland, association of upper gisogb, et al. uk guidelines for the management of acute pancreatitis. gut. 2005;54 suppl 3(suppl 3):iii1-iii9. 20. azzeri c, tarquini r, giunta f, gensini gf. glucose dysmetabolism and prognosis in critical illness. internal and emergency medicine. 2009;4(2):147. 21. ajbaf f, mojtahedzadeh m, abdollahi m. mechanisms underlying stress-induced hyperglycemia in critically ill patients. clinical practice. 2007;4(1):97. 22. azmak d. methanol related deaths in edirne. legal medicine. 2006;8(1):39-42. 23. kurtas o, imre ky, ozer e, can m, birincioglu i, butun c, et al. the evaluation of deaths due to methyl alcohol intoxication. 2017. 24. brent j, mcmartin k, phillips s, aaron c, kulig k. fomepizole for the treatment of methanol poisoning. new england journal of medicine. 2001;344(6):424-9. 25. megarbane b, borron sw, trout h, hantson p, jaeger a, krencker e, et al. treatment of acute methanol poisoning with fomepizole. intensive care medicine. 2001;27(8):1370-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e41 rev i ew art i c l e epidemiological and clinical aspects of covid-19; a narrative review goodarz kolifarhood1,3, mohammad aghaali1, hossein mozafar saadati1, niloufar taherpour1, sajjad rahimi1,2, neda izadi3, seyed saeed hashemi nazari4∗ 1. department of epidemiology, school of public health & safety, shahid beheshti university of medical sciences, tehran, iran. 2. modeling in health research center, shahrekord university of medical sciences, shahrekord, iran. 3. student research committee, department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 4. prevention of cardiovascular disease research center, department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. received: february 2020; accepted: march 2020; published online: 1 april 2020 abstract: there are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of covid-19 as a new emerging epidemic. in addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. however, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities. keywords: covid-19; severe acute respiratory syndrome coronavirus 2; epidemiology; public health; communicable diseases, emerging cite this article as: kolifarhood g, aghaali m, mozafar saadati h, taherpour n, rahimi s, izadi n, hashemi nazari s s. epidemiological and clinical aspects of covid-19; a narrative review. arch acad emerg mede. 2020; 8(1): e41. 1. introduction over the past few decades, a large number of people have been affected with the 3 epidemics caused by coronavirus family (sars-2003, mers-2012, and covid-2019) in the world. nevertheless, there is substantial genetic dissimilarity between pathogens of the three previous epidemics, in particular mers with covid-19. in the previous epidemics, initial hotspots of diseases were middle east, saudi arabia (mers) and china and animal to human, and then human to human transmissions of pathogens were reported in other countries (1,2). for covid-19, as suggested by epidemiological evidence in ∗corresponding author: saeed hashemi; department of epidemiology, school of public health & safety, shahid beheshti university of medical sciences (sbmu), tehran, iran. email: saeedh_1999@yahoo.com tel: +98 21 81455102 fax: +98 21 81454357 china (at the time of writing this paper), this outbreak began from a seafood and live animal shopping center in wuhan, hubei province on december 12, 2019. however, similar to two previous epidemics, the current epidemic also switched to human to human transmission immediately, and swept through most regions in china even faster than the previous pandemics (3). recent epidemics of viral respiratory diseases in the world have started from china (except for mers that originated in saudi arabia), and there are several possible reasons for this. from an economic perspective, china has emerged as one of the leading countries in the production of various commodities, especially in the past decade, and given the enormous volume of trade, tourism and military transactions with other countries, there was no doubt that the virus would spread to other parts of the world (4). china has already acknowledged the possibility of a new virus epidemic in the future and has consequently stressed the importance of formulating a policy to improve the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. kolifarhood et al. 2 healthcare system and preparedness after the two previous epidemics. this country rearranged its health plan in the wake of mers epidemic in 2012, establish a new web-based service for quick alarming in case of an emerging disease with unknown origin through common surveillance system. in the wake of conditions ensuing sars epidemic and severe criticisms levelled by international institutions regarding delayed provision and sharing of data by china government, this country has started extensive collaborations with international institutions from the early days of the recent epidemic, and established a publicly available database of line list of cases through coordinating with johns hopkins university (5). moreover, china scaled up public health measures and quarantined many cities, bearing the grave economic consequences of this action to prevent the spread of the disease to other parts of the world. although, china has been struggling with tough conditions in the previous month, reduction in the number of incidence cases and interruption of transmission indicate its successful measures to control the recent epidemic and highlight the importance of timely and appropriate decisions through activating human and material resources for addressing a serious global threat (6). number of covid-19 cases has risen substantially in the world compared to sars and mers, and it would probably take longer to halve the disease cases; meaning that control measures would have to be in place for a longer period of time. who has announced that coronavirus epidemic is progressively increasing in three countries, including italy, south korea, and iran. the shared string that links these three countries is the pandemic of mers in 2013, which was transmitted through close human-to-human contacts (7). this study was carried out to review different epidemiological and clinical aspects of the new emerging disease along with specific measures by countries in the community level. 2. methods 2.1. search methods and strategies for identification of studies literature search was performed in "pubmed", "web of science", "scopus", "sciencedirect" and also in "jama", "bmj", "oxford" and "the lancet" journals using following terms: coronavirus, covid-19 and 2019-ncov, to find articles published from january 5 to february 28, 2020. moreover, we used the findings of literature retrieved via searching authoritative texts and hand searches in who reports. we checked the reference lists of all studies identified by the above methods. studies were excluded if used old data, had inappropriate topics and were not pertinent to the focused purpose of the study. 2.2. data collection and analysis in order to identify studies meeting the inclusion criteria, seven review authors screened the titles and abstracts of all retrieved records. the studies were selected independently and the results were discussed to make the final selection. after reading the full text of all potentially eligible articles, a final decision was made for each study. 2.3. data extraction and management extraction of data was performed by the same seven review authors who conducted the study selection independently, using a structured form that contained study characteristics including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management, special measures in community level and health care facility. any disagreement was discussed after completion of data collection process and reviewers were consulted for each topic. 3. results 3.1. genetic differences between sars, mers, and covid-19 epidemics the animal reservoir of the virus has not yet been identified, but genomic of covid-19 is so similar to bat coronavirus (98%), reinforcing the presumption that the virus was transmitted by an animal in the shopping center in wuhan. with regard to genomic similarity, the virus differs from its predecessors, namely sars (79%) and mers (50%). as indicated by genetic data, cvoid-19 pathogen is classified as a member of the beta-coronavirus genus, and can bind to the angiotensinconverting enzyme 2 receptor in humans (1,2). 3.2. transmission and incubation period human to human transmission via either respiratory droplets or close contacts was initially proposed as the main routes of transmission of the pathogen based on experience gained in the previous two epidemics caused by coronaviruses (mers-cov and sars-cov )(8). according to the world health organization (who) report, 2019-ncov is a unique virus that causes respiratory disease, which spreads via oral and nasal droplets. moreover, the pathogen of covid-19 can float in the air in the form of aerosols and cause infection in healthy people (9). evidence of a study in singapore revealed higher loads of virus in confirmed cases of covid-19 in early stages of the disease, which decreased dramatically over time (10). there is a limited number of evidence on oral-fecal transmissibility of the pathogen. however, covid-19 rna was found in fecal specimens of 2 to 10% of confirmed patients with gastrointestinal symptoms this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e41 such as diarrhea (11,12), so fecal-oral transmission should be taken into account as a probable route through case investigation. incubation period (the time from infection to the onset of symptoms) for the new pathogen varies from 2 to 14 days in human to human transmission (13). furthermore, median incubation period was reported as 5-6 days (ranged from 014 days) in who report (14). studies that were conducted on those who had traveled to wuhan and guangdong mean incubation period of 4.8 (±2.6) days was reported. in some other studies the mean incubation period was reported to be 6.4 days (15,16), while another study in china reported longer incubation times up to 24 days (13). 3.3. infectivity an important question about covid-19, which has raised much concern among health care providers, health policy makers and the general population, is the degree of transmissibility or contagiousness of the coronavirus (infectivity). in general, epidemiologists use mathematical formulas with clear and acceptable assumptions to calculate the infectivity index. for this purpose, "basic reproduction number" termed r0 is used, and it indicates the expected number of cases directly infected by one contagious case in a population that everyone is supposed to be susceptible. for viral pathogens in mers and sars epidemics, the index was approximated to be 2, indicating that each infected person could infect two people on average in an effective contact. however, for covid-19, the calculated value in a study was slightly higher and the index value based on data calculated in wuhan, china was 2.2 (95% ci, 1.4 to 3.9) (17) and it shows that the infectivity of covid-19 is higher than previous epidemics originated by coronavirus (18). in other studies, r0 has been reported with different values, the lowest of which corresponds to the who report of 1.95 (1.4-2.5) (19) and the highest value is 6.47 (95% ci 5.71–7.23) (20). a review study estimated an average r0 for covid-19 of 3.28 with a median of 2.79 and an iqr of 1.16 (21). as an explanation for variety of the calculated indices is that different calculation methods were used and calculations were done at different times of epidemics. as previously noted, certain assumptions have been made in calculation of this index. initial reports on a family in one of the provinces of china show that all six-members of a family, aged 10-66 years were infected within a short period after one member returned from wuhan (8). as a conclusion, this index is changing over time, and its reduction may reflect effectiveness of preventive measures, so that reaching a value less than one (less than one new case per effective contact with an infected person and transmission) implies that the epidemic is controlled in the community (6). 3.4. pathogenicity an important concern in the recent pandemic is the capability of the pathogen to establish and induce infection with different clinical manifestations in human. according to who report, about 82 percent of covid-19 patients have mild symptoms and were recovered immediately. as of 20 february, there were 18264 (24%) recovered cases in china and recovery and mortality rates of the disease among severe cases in guangdong were 26.4% and 13.4%, respectively. median time for onset of symptoms to recovery in mild and severe cases was 2 and 3-6 weeks, respectively. furthermore, time interval between onset and developing severe symptoms such as hypoxia was one week (22). in case studies that were conducted outside of mainland china, time of onset of symptom(s) to recovery was 22.2 days (95% confidence interval 18-83). moreover, average time of onset of symptom(s) to death varies from 20.2 (95% confidence interval 15.1-29.9) to 22.3 days (95% confidence interval 18-82) (23,24). results of a case-series study on six infants (45-days to one-year) infected with covid-19 in china indicated mild symptoms of the disease in this age group with no need for further intensive care (25). according to who report, covid-19 disease among children seems to be rare with mild symptoms, about 2.4% of total cases were reported in children and adolescents (aged under 19 years), while older cases aged over 60 years and those with a background of chronic diseases were at higher risk of developing severe disease and death (22). even though age is an important deterministic factor for severity of symptoms, other risk factors such as having a history of underlying diseases and/or co-infection with other infections like influenza virus and klebsiella may accelerate the progress of symptoms and lead to poor prognosis of the disease (26). however, findings from a study in singapore shows that infected patients with no history of underlying diseases may also develop severe disease and need for intensive care (4). 3.5. virulence the virulence of a disease is usually measured on the basis of indicators such as mortality rate and disability. compared with the previous two epidemics (sars and mers), the case fatality rate was lower and approximately 2% in covid-19, and only less than 15% of patients would seek hospital services. however, the case fatality rate of sars and mers was 10% and 34%, respectively (18). results of a study in china revealed the overall case fatality rate of 2.3% for covid-19 (27) and some studies reported case fatality rate of 0.9% in beijing (28). in another study, jung and colleagues reported a confirmed case fatality risk of 5.3% to 8.4% for covid19(23). however, due to the rapid spread of covid-19, there this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. kolifarhood et al. 4 is a higher number of death cases in the recent pandemic (n=3043, up to 02 march 2020) compared to sars and mers (n=1871) (29). there is a poor prognosis for the disease in middle and older aged patients (28). in a study on 44672 confirmed cases in china, case fatality rate was highest in the group of over 80 years (14.77%), followed by the age group between 70 to 80 years (7.96%) and no mortality was reported in age group below 10 years (30). even though death outcome is uncommon in young people, a few deaths are reported in this age group in china and iran. availability of and access to healthcare facilities has likely contributed to increase in death outcome. as a probable explanation for the difference between fatality rate in wuhan (3%) and other provinces (0.7%) in china, death rates are likely affected by shortage in health resources due to increasing number of patient who had sought diagnosis and treatment services in the early phase of the epidemic in wuhan (31). 3.6. immunogenicity exploring and understanding the immunogenicity of covid-19 is essential for developing the most effective treatment regimens and vaccine. however, evidence on immunogenicity of covid-19 is limited. study on b-cell and t-cells epitopes revealed that sars-cov and the virus causing covid-19 had identical proteins (32). a few clinical trials have evaluated the efficacy of new vaccines in mers-cov and sars-cov. results of these studies in phase-1 showed some degree of efficacy and one of these studies has been certified to begin phase-2 (33,34). absence of clinical symptoms, respiratory lesions in ct scan and two negative rt-pcr tests in two consecutive days are introduced as criteria of discharge from hospital or quarantine center in china (35). however, recent studies reported several cases of covid-19 with clinical manifestations of the disease along with a positive test after discharging from hospital (36,37). false positive and false negative results have been reported in rt-pcr test (10,38); hence, hospitals in china have considered additional antibody test (negative igm and positive igg results) as a recovery criteria and discharge requirement (39). in conclusion, recurrence of covid-19 in recovered cases highlights the necessity for development of a more effective vaccine. 3.7. diagnosis pathogen of covid-19 has been detected in upper and lower respiratory tracts in initial assessments. moreover, viral rna has been detected in fecal and blood samples in later studies. according to who guideline, laboratory diagnosis of covid19 is based on a positive rt-pcr test. target gene for diagnosis may be different by country. accordingly, target genes for screening and confirmatory assays by rt-pcr are orf1ab and n in chinese laboratory protocol, while rdrp, e and n are checked in germany. furthermore, three targets in n gene are considered in the us protocol (40). rt-pcr is an expensive test and no access to diagnostic facility during covid-19 pandemic advocates conducting new researches on other diagnostic approaches such as chest ct. however, results of recent studies in china demonstrate low specificity for this diagnostic approach (41). as a critical point in diagnostic studies, accuracy of a new test is compared to the gold standard. this comparison resulted in lower values of diagnostic accuracy for the new test. on the other hand, the sensitivity and specificity of a test depend on the severity of cases, which may vary between different populations according to their type of surveillance system (42). in the mentioned study that compared ct scan with rt-pcr as a gold standard, sensitivity of ct scan was appropriate (41). however, the study population consisted of suspected cases and generalizability of the findings is questionable (43). furthermore, the large number of hospitalized cases due to false positive results by ct scan may increase the risk of transmission to healthy people. on the other hand, rt-pcr test may be subject to some limitations, especially in the earlier phase of an epidemic, as the specialists should be trained for running related procedures and interpretation of results. moreover, false negative results due to either low quality of specimen in use or inadequate number of organisms in the samples are introduced as main challenges (44). results of a recent study on rapid igm-igg combined test revealed some limitation for rt-pcr test as a standard diagnostic method for covid-19. the following limitations were indicated for rt-pcr test: long turnaround times, complex operation, and need for quality controlled laboratories, expensive equipment and trained specialists (38). 3.8. surveillance the outbreak surveillance is the anticipation, early warning, prompt detection and response to unusual increase in the number of cases. establishing a surveillance system for a new epidemic is believed to be a core intervention in controlling the disease (45). surveillance system data provides reliable information for epidemiologists to identify weak chains of transmission and facilitates evidence-based decisions by policymakers both inside and outside the healthcare service. moreover, updating and sharing interpretations of data with media, especially in earlier phase of an epidemic, will aid community engagement and participation in control activities and prevention of spreading rumors. although, it may be too soon to compare the effectiveness of surveillance systems for covid-19 epidemic in different countries, it seems that the chinese surveillance system is highly effective as it ensures timely detection, recording, tracking, updating and sharing information on media for an outbreak with unknown this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e41 origin and high burden of cases (4). in a large number of countries, the initial focus of the surveillance system for civid-19 is examination of all suspected cases with symptoms of the disease (mostly fever) and all people with a travel history to china or visiting chinese travelers or citizens it the previous two weeks. however, this type of screening program mainly relies on fever cases and those with direct flights from china, so it misses pre-symptomatic cases as well as infected travelers who are arriving from regions with high burden of disease via indirect flights, which could be a source of infection in covid-19-free countries (46). in a communicable disease outbreak, essential data are usually collected in parallel from different available information sources in the country including data of weekly outpatient visits to health care centers and hospital referrals with a chief complaint of fever, data of weekly inpatient fever cases and deaths with unknown origin (45). furthermore, increase in the number of cases and deaths due to pneumonia may raise an alarm in covid-19 free areas. a prerequisite for establishing a surveillance system is to provide basic laboratory facilities, particularly at "point of care" (10). this system should be constantly monitored and evaluated using sensitive indicators to ensure the quality of case detection, diagnosis and management. detection of primary confirmed cases with poor prognosis in early phase of the epidemic without any link to confirmed cases from other regions emphasis on the insensitivity of a national and local surveillance systems and low performance of control activities against the disease in community level. in this case, it should be immediately addressed and capability and capacity of the surveillance system should be checked. 3.9. examples of surveillance systems in different countries (47) national authorities are actively looking for cases in all provinces of china and efforts for finding additional cases inside and outside of wuhan city have been expanded. moreover, active and reactive case detection along with tracing close contacts have been started in medical institutions. the department of disease control in thailand scaled up the emergency operations center to level 3 to closely monitor the ongoing situation in both national and international levels. this country has started a screening program to check for fever in all travelers who arrived from wuhan through direct flights in airports. japan’s ministry of health requested local health governments to be aware of the respiratory illnesses in wuhan using the existing surveillance system for serious infectious illnesses with unknown etiology. it has strengthened surveillance for undiagnosed severe acute respiratory illnesses. quarantine and screening measures have been intensified for travelers from wuhan at the points of entry. furthermore, national institute of infectious disease (niid) established an in-house pcr assay for covid-19. contact tracing and other epidemiological investigation are ongoing in the republic of korea to prevent the spread of the disease. the government has scaled up the national alert level from blue (level 1) to yellow (level 2 of the 4-level national crisis management system). surveillance of pneumonia cases has been strengthened in health facilities nationwide and quarantine and screening measures have been enhanced for travelers from wuhan at the points of entry. the us centers for disease control and prevention (cdc) activated its emergency response system to provide ongoing support against covid-19. screening of passengers on direct and indirect flights from wuhan china to the 3 main ports of entry in the united states has begun and will expand to atlanta and chicago in the coming days. cdc deployed a team to support ongoing investigation in the state of washington and tracing close contacts following the first reported case of covid-19. 3.10. clinical case management diagnosis of covid-19 based on clinical manifestations is complicated and initial symptoms of the disease are usually nonspecific. a large number of patients present to clinics and health centers with mild common cold symptoms such as dry cough, sore throat, low-grade fever or body aches. patients usually go to the emergency departments if the symptoms of the clinical manifestations worsen after a few days. because of the wide spectrum of clinical symptoms, research on biomarkers and clinical criteria predicting prognosis is of high priority to enable differentiating cases that require further interventions in the early phase of the disease (10). no approved drug regimen has been introduced to treat infected cases so far, antiviral treatments are used to alleviate the disease symptoms. studies on remedesevir, as an antiviral agent, revealed its in vitro activity against the covid-19 virus and its safety was proven in ebola trials. another proposed treatment is chloroquine, an old drug for treatment of malaria, with apparent effectiveness and acceptable safety against covid-19 associated pneumonia (48,49). evaluating the efficacy of anti-influenza drugs such as umifenovir and oseltamivir against covid-19 virus is interesting but lacks any biological plausibility. using monoclonal antibodies has been suggested as an attractive choice among inactive prophylactic methods; however, its effectiveness has not been proven in other viral respiratory diseases and influenza, yet (50,51). steroids and methylprednisolone seem to be widely used in the recent pandemic. however, in case of mers, it has been shown that the drug prolongs the presence of the virus and who does not recommend its use for covid19, except for patients with acute respiratory distress synthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem g. kolifarhood et al. 6 drome (ards) (52,53). the effectiveness of other medicines and regimens such as chloroquine, vitamin c, and chinese medicine, as well as lopinavir/ritonavir combination therapy and remedesevir are being evaluated in china. even though randomized clinical trials are important for improving prognosis and interrupting transmission of disease, researchers and healthcare providers should concentrate on alleviation of the disease among subgroups of patients and in different phases of the disease (54). in addition, since the emerging virus has become a serious global concern, there is a need for rapid development of a vaccine. there are a few vaccine candidates developed in response to outbreak. however, an effective anti-viral medication or a vaccine that has been evaluated for safety and efficacy against covid-19 is not available yet, and most vaccines are still in the preclinical testing stage (55,56,57). 3.11. special intervention in community level so after the rise of an emerging disease, goverments have a special responsibility to balance between civil liberties and special measures for protecting susceptible populations (46). however, three components of "scientific", "voluntary" and civil liberty should be considered as guiding principles for decision-making and operating each special protective measure at the community level. through their experiences in previous communicable disease epidemics, us public health authorities found that enhanced screening programs, monitoring healthy people and quarantine at the community level were not effective measures against progressive spreading of disease. therefore, specific regulations and waivers were declared to prevent traveling to mainland china and flights to and from china were temporarily suspended. passengers and us citizens with a history of traveling to china during the previous month were encouraged to stay home and self-quarantine for up to 14 days. however, these interventions and recommendations were deemed insufficint, so public health experts warned about expanding transmission throughout the country in the coming weeks as a consequence of population movements and large scale spread of the disease all over the world (46,58). even though children are important sources of influenza virus transmission in the community, initial data analysis on covid-19 indicated that children were mainly infected from adults rather than the other way around. however, clinical attack rates are low in children and teenagers (0-19) (59), so this age-group may contribute to continuous transmission in the communty. therefore, countries with high prevalnece of the disease, such as china, iran, italy, south korea and japan, closed or postponed the start of school and extended holidays. other special measures considered for control of the pandemic at community level include: cancellin mass gatherings, religious services, tourism, cultural and sport events, concerts and other events. in the mentioned countries, healthcare authorities issued travel ban to and from affected areas and allowed non-essential personnel and employees to work from home. 3.12. special interventions for healthcare providers healthcare authorities are responsible for predicting and supplying the essential protective equipment for general population as well as healthcare providers. by ensuring their availability through effective supply chain management, they gain public trust. they also have to plan for deploying healthcare perssonel from less affected areas to epidemic regions (10). with this method, a large number of medical staff and nurses were voluntarily deployed to wuhan, china (60). according to primary reports from china and singapre, working with protective equipment for a long time is cumbersome for healthcare providers and they are under tremendous stress due to probability of being infection and transmitting the disease to their families through close contact (57). the high rates of hospital infection in the recent pandemic emphasizes the importance of regular examination for symptoms among healthcare providers who are in close contact with confirmed patients in order to isolate them in case of positive laboratory test. 4. conclusion covid-19 pandemic is a major international test for the medical community, revealing weaknesses in management of emerging viral diseases and reminding us that communicable diseases must never be underestimated or dealt with using insufficient resources. the present situation also enables governments to evaluate their capabilities and capacities to organize human and material resources, share and analyze data in a timely manner and cooperate with media, journalists and local communities to implement control activities. 5. declarations 5.1. acknowledgements we would like to thank the vice-chancellor in research affairs of shahid-beheshti university of medical sciences for technically supporting this study. ethical approval was granted by the iran national committee for ethics in biomedical research, tehran, iran (ir.sbmu.retech.rec.1398.874). 5.2. authors contributions kolifarhood participated in designing the project and literature review, aghaali, mozafar-saadati, taherpour, rahimi this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e41 and izadi wrote the manuscript and participated in literature review and hashemi was the supervisor of the study and checked the quality of the study. all authors read and approved the final manuscript. authors orcids goodarz kolifarhood: 0000-0002-8164-6633 mohammad aghaali: 0000-0003-3417-1580 hossein mozafar saadati: 0000-0002-5992-3710 niloufar taherpour: 0000-0002-8336-0671 sajjad rahimi: 0000-0002-2359-0037 neda izadi: 0000-0002-6373-1113 saeed hashemi: 0000-0002-0883-3408 5.3. funding support this project was supported with grant 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8(1): e55 or i g i n a l re s e a rc h lobar distribution of covid-19 pneumonia based on chest computed tomography findings; a retrospective study sara haseli1, nastaran khalili2∗, mehrdad bakhshayeshkaram1, morteza sanei taheri3,4, yashar moharramzad4 1. chronic respiratory diseases research center, national research institute of tuberculosis and lung diseases (nritld), shahid beheshti university of medical sciences, tehran, iran. 2. school of medicine, tehran university of medical sciences, tehran, iran. 3. iranian society of radiology, tehran, iran. 4. department of radiology, shohada-e-tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 18 april 2020 abstract: introduction: computed tomography (ct) imaging has quickly found its place as a beneficial tool in the detection of coronavirus disease 2019 (covid-19). to date, only a few studies have reported the distribution of lung lesions by segment. this study aimed to evaluate the lobar and segmental distribution of covid-19 pneumonia based on patients’ chest ct scan. methods: this was a retrospective study performed on 63 iranian adult patients with a final diagnosis of covid-19. all patients had undergone chest ct scan on admission. demographic data and imaging profile, including segmental distribution, were evaluated. moreover, a scoring scale was designed to assess the severity of ground-glass opacification (ggo). the relationship of ggo score with age, sex, and symptoms at presentation was investigated. results: among included patients, mean age of patients was 54.2 ±14.9 (range: 26 81) years old and 60.3% were male. overall, the right lower lobe (87.3%) and the left lower lobe (85.7%) were more frequently involved. specifically, predominant involvement was seen in the posterior segment of the left lower lobe (82.5%). the most common findings were peripheral ggo and consolidation, which were observed in 92.1% and 42.9% of patients, respectively. according to the self-designed ggo scoring scale, about half of the patients presented with mild ggo on admission. ggo score was found to be equally distributed among different sex and age categories; however, the presence of dyspnea on admission was significantly associated with a higher ggo score (p= 0.022). cavitation, reticulation, calcification, bronchiectasis, tree-in-bud appearance and nodules were not identified in any of the cases. conclusion: covid-19 mainly affects the lower lobes of the lungs. ggo and consolidation in the lung periphery is the imaging hallmark in patients with covid-19 infection. absence of bronchiectasis, solitary nodules, cavitation, calcifications, treein-bud appearance, and reversed halo-sign indicates that these features are not common findings, at least in the earlier stages. keywords: covid-19; pneumonia, viral; tomography, x-ray computed; lung injury cite this article as: haseli s, khalili n, bakhshayeshkaram m, sanei taheri m, moharramzad y. lobar distribution of covid-19 pneumonia based on chest computed tomography findings; a retrospective study. arch acad emerg med. 2020; 8(1): e55. ∗corresponding author: nastaran khalili; school of medicine, poursina avenue, tehran university of medical sciences, tehran, iran. tel: +982122567222, email: nkhalili71@gmail.com 1. introduction an outbreak of pneumonia associated with a novel coronavirus, now commonly known as sars-cov-2, emerged in wuhan, china in december 2019. patients infected with this novel virus manifested with symptoms of severe pneumonia, including fever, fatigue, dry cough, and acute respiratory distress (1). since the announcement of covid-19 by the world health organization (who) as a pandemic, elimination of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haseli et al. 2 this disease has turned into a global health priority (2). however, without optimizing our knowledge about the efficient diagnosis and treatment of this disease, increase in infection and mortality rates is inevitable. primary investigations showed that reverse transcriptasepolymerase chain reaction (rt-pcr) is associated with a low detection rate at initial presentation, as well as being associated with several weaknesses such as limited number of kits, possibility of false negative rt-pcr results, and an undesirable delay in diagnosis (3). thus, it was essential to find a complementary strategy for time-efficient detection of this disease. imaging quickly found its place as a critical tool, aiding in the diagnosis of patients suspicious for covid-19 infection. so far, the literature has mainly emphasized on the role of chest computed tomography (ct) scan for screening and identifying covid-19 patients, as well as evaluating severity and disease progression. in comparison to radiography, chest ct scan imaging is a more reliable and sensitive method to diagnose and assess covid-19, especially in epidemic regions (4). evaluating chest ct findings in combination with clinical symptoms and laboratory tests aids in the medical decision making for covid-19 disease. in many regions of iran, ct scan is more available than rt-pcr, the current standard confirmatory test of covid-19. in these regions, chest ct is used as one of the first modalities for initial evaluation of suspected cases, aiding in prompt management before confirmation of diagnosis by pcr (5, 6). the primary findings of covid-19 on ct imaging are those of atypical pneumonia or organizing pneumonia with significant overlap with other acute lung injuries such as viral infection (especially influenza), drug toxicity, vasculitis, and connective tissue disease (7). in a recent study evaluating prediction models for diagnosis and prognosis of covid-19 infection, one of the mentioned limitations was that reported data from outside of china is scarce (8). moreover, although multiple studies have been published reporting ct-imaging features of covid-19 pneumonia; few studies have investigated the distribution of lung lesions by segment. in this study, we aim to evaluate the pattern of covid-19 pneumonia segmental involvement, by presenting chest ct-scan findings of 63 patients. also, we have designed a novel scoring scale to report the extension and severity of ground-glass opacification (ggo) in our patients and assess its association with age, sex, and presenting symptoms. 2. methods 2.1. study design and setting this was a retrospective study performed on 63 adult patients with a final diagnosis of covid-19 who had undergone chest ct-scan in a tertiary referral hospital in tehran, iran, from february to march, 2020. all patients had presented within one week of symptom onset. diagnosis of covid-19 was confirmed by a positive rt-pcr for sarscov-2 obtained from a nasopharyngeal swab specimen. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences (code: ir.sbmu.nritld.rec.1399.028). due to the retrospective nature of the study and no potential risk of harm to patients, the institutional review board (irb) of shahid beheshti university of medical sciences waived written informed consent. also, patients’ personal information was de-identified and kept confidential. 2.2. participants patients were consecutively selected. the exclusion criteria were age < 18 years, asymptomatic cases with only abnormal imaging, and history of previous underlying lung disease. 2.3. data gathering demographic data including patients’ age, sex, and initial symptom at presentation was collected. all patients had undergone at least one non-contrast chest ct-scan with reconstructions of the volume at 1 mm to 2.5 mm slice thickness on the first day of admission before receiving any antiviral treatment. in patients who had more than one chest ct image, only the initial ct scan (on admission) was evaluated in this study. ct images were reviewed by three board certified radiologists using a viewing console. all of the radiologists were blinded to the lab data, clinical features, and patients’ diagnosis. first, imaging findings were interpreted independently and then, final decision was made by consensus. no negative control cases were included in this study. imaging features including type of opacity, ggo severity score, and presence of other abnormal findings (such as pleural effusion, interlobular septal thickening, cavitation, reticulation, calcification, bronchiectasis, presence of discrete nodules, and reversed halo sign) were assessed. ggo was defined as increased lung attenuation with preservation of bronchial structures and pulmonary vessels, and consolidation was defined as opacification with obscuration of vascular margins and airway walls. reversed halo sign was considered a focal rounded ggo surrounded by a ring-like consolidation. 2.4. ggo scoring the extension of ggo was measured based on the following scoring scale: involvement of less than 1/3 of segments=1; involvement of 1/3 to 2/3 of segments=2; involvement of more than 2/3 of segments=3. the greatest score was considered as the final score. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e55 table 1: patients’ baseline characteristics variable number(%) sex male 38 (60.3) female 25 (39.7) age (year) 20-39 12 (19) 40-59 28 (44.4) ≥ 60 23 (36.5) symptom at presentation dyspnea 33 (52.3) fever 45 (71.4) cough 30 (47.6) headache 6 (9.5) myalgia/ fatigue 9 (14.3) gastrointestinal symptoms 1 (1.5) 2.5. statistical analysis categorical variables are reported as number (percentages) and continuous variables are reported as mean ± standard deviation (sd). we evaluated the association of segmental distribution with the age group and sex of patients by conducting chi-square or fisher’s exact test. mann-whitney u test or kruskal-wallis test was used to assess the relationship of ggo score with age group, sex, and common initial symptoms (fever, dyspnea, and cough) at presentation. all statistical tests were performed using spss v.23 (ibm inc., chicago, il, usa). statistical significance was fixed at 0.05. 3. results 3.1. baseline characteristics of participants a total of 63 patients (38 male and 25 female) were included. mean age of patients was 54.2 ±14.9 (range: 26-81) years old (60.3% male). the most common symptoms at presentation were fever (71.4%), dyspnea (52.3%), and cough (47.6%), respectively. table 1 shows patients’ baseline characteristics. 3.2. chest ct findings all patients had abnormal chest ct scan consistent with viral pneumonia. table 2 shows the frequency of lung lesions based on segmental involvement and also the frequency of different imaging features. the most common imaging feature among our patients was peripheral ggo (92.1%) and consolidation (42.9%). 50.7% of the patients had a mild ggo. pleural effusion was seen in only one patient. tree-in-bud appearance, cavitation, reversed halo sign, reticulation, calcification, bronchiectasis, and nodules were not identified in any of the cases. overall, lower lobes of both sides were found to be more frequently involved in our patients. predominant lobar involvement was seen in the posterior segment of the left lower lobe table 2: chest computed tomography (ct) findings of covid-19 patients location number(%) right upper lobe apical 24 (38.1) posterior 35 (55.5) anterior 23 (36.5) right middle lobe lateral 41 (65.1) medial 11 (17.5) right lower lobe superior 49 (77.8) posterior 47 (74.6) medial 40 (63.5) anterior 26 (41.3) lateral 45 (71.4) left upper lobe apicoposterior 22 (34.9) anterior 24 (38.1) superior lingula 26 (41.2) inferior lingula 25 (39.7) left lower lobe superior 39 (61.9) anteromedial 22 (34.9) lateral 48 (76.2) posterior 52 (82.5) imaging characteristics bilateral 53 (84.1) peripheral ggo 58 (92.1) consolidation 27 (42.9) peri-bronchovascular ggo 13 (20.6) sub pleural band 6 (9.5) interlobular septal thickening 4 (6.3) pleural effusion 1 (1.5) ggo severity mild 32 (50.7) moderate 20 (31.7) severe 11 (17.4) ggo: ground-glass opacification. (82.5%) followed by the superior segment of the right lower lobe (77.8%) and the lateral segment of the left lower lobe (76.2%), respectively. on the other hand, medial segment involvement of the right middle lobe was the least reported finding (17.5%). 3.3. segmental involvement based on age and sex the inferior lingula (p = 0.012) and the apicoposterior segment of the left lower lobe (p = 0.045) showed a significantly higher involvement among females. moreover, the anterior (p = 0.017) and posterior (p = 0.043) segment of the right upper lobe, the lateral (p = 0.019) and medial (p = 0.015) segment of the right lower lobe, and the superior segment of the left lower lobe (p = 0.029) were more commonly involved in patients ≥60 years old. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haseli et al. 4 3.4. ggo score ggo score was found to be equally distributed among sex (p = 0.098) and age (p = 0.846) categories. existence of dyspnea at presentation was significantly associated with a higher ggo score (p= 0.022) 4. discussion in this study we have reported chest ct imaging results of patients with laboratory-confirmed covid-19 pneumonia. our results revealed that the most common finding was peripheral ggo followed by consolidation. cavitation, reticulation, calcification, bronchiectasis, tree-in-bud appearance, reversed halo-sign, nodules and pleural effusion were not common findings in the chest ct scan of our patients. in terms of segmental distribution, most commonly, involvement was seen in the posterior segment of the left lower lobe. moreover, certain segments and lobes were more frequently involved based on age and sex of patients. the results of our study indicated that, overall, lower lobes of the lungs were more frequently involved. specifically, the posterior segment of the left lower lobe, the superior segment of the right lower lobe and the lateral segment of the left lower lobe were predominantly involved. consistent with our findings, a recent study by song et al., also found lower lobe involvement in 90% of covid-19 patients (9). another study also pointed to the same finding that peripheral and lower lobe involvement is more common (10). yang et al. reported the posterior basal segments of the right and left lower lobes as the most involved sites in 102 patients with covid19 pneumonia (11). however, they did not report the difference of segmental distribution with respect to age and sex. our study demonstrated that certain segments and lobes are more frequently involved in females or older patients. this might provide clue to radiologists to pay particular attention to these segments when reviewing the imaging of these populations; yet, more studies are warranted for a definite conclusion. we observed that the majority of patients presented with peripheral distribution of lung lesions in imaging. this observation was previously reported by several other studies (10, 12, 13). however, one study has reported peripheral distribution in only 33% of investigated patients (14). although various ct findings were observed in our cases, almost all cases had bilateral ggo in sub-pleural areas. it seems that exudative fluid accumulation within the alveolar space is the cause of this multi-lobar appearance. since the predominant pattern is ggo, the superiority of ct scan over chest radiography is justified due to its higher resolution. it is assumed that low-dose ct scan might also be helpful; not only for diagnosis, but also for reducing radiation exposure, although further studies are needed (5). the majority of studies published so-far have also mentioned ggo, consolidation, and bronchial dilation as the main characteristic findings (4, 5, 14-19). this pattern of involvement is not pathognomonic and resembles that of other viral pneumonia, in particular, influenza. other pathologies such as aspiration pneumonia also present with bibasilar consolidation similar to covid19 infection. similar radiologic patterns are also found in interstitial lung diseases, such as organizing pneumonia or non-specific interstitial pneumonitis (nsip), in which predominant peripheral ggo or diffuse ggo is observed. bilateral patchy areas of ggo are also found in conditions such as lung contusion in the setting of severe chest trauma (18, 20, 21). thus, decision making based on appropriate clinical findings is crucial for correct diagnosis. there was no sign of cavitation, reticulation, calcification, bronchiectasis, tree-in-bud appearance, reversed halo-sign, and nodules in any of our patients and only one patient had pleural effusion. interestingly, the absence of these imaging features in covid-19 has also been demonstrated by several other studies (4, 13, 14, 18). however, it is probable that these features develop in long-term, and thus, it is not possible to reach a conclusion through investigation of early imaging. reversed halo sign is usually present in invasive fungal infections such as aspergillosis, vasculitis and even tumor metastasis; however, viral infection is also another cause of this appearance. although this sign has been seen in some covid19 cases, it is considered a late finding (5, 18). our results revealed that less than one-fifth of patients demonstrate severe ggo on admission. it has been shown that after two weeks from initial symptoms, as consolidation begins to resolve, ggo becomes more extensive (15). this might explain the low rate of severe ggo observed in this study, as our patients were investigated within one week of symptom onset. we observed a significant association between elevated ggo score and presence of dyspnea at presentation, although it did not correlate with other symptoms such as cough and fever. also, severity of ggo was not affected by patients’ age and sex. notably, zhou and colleagues also reported that dyspnea on admission was associated with increased odds of death, while fever and cough were not (22). previous studies have stated that increase in the extent and density of ggo on ct can be used as a prognostic marker (13, 14). several studies have displayed a significant association between higher ct score (based on extent of lung opacification) and a more severe course of covid-19 disease (11, 23-25). in a recent study by song et al., patients were classified into severe and non-severe groups based on clinical and imaging criteria. in this study, a self-designed ct scoring system was used as a marker for assessing the severity of the disease, showing a markedly higher ct score among patients with severe disease. consistent with our study, they did not find a significant association between sex and disease severity; however, older cases were more likely to develop severe this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e55 illness (23). thus, although we were not able to measure the relationship between ggo severity and disease outcome, the significant association of dyspnea with a higher ggo score might indicate that the existence of this symptom at presentation indicates worse prognosis. this study had various limitations. first, it only included adult cases. second, it had a relatively small sample size. moreover, we only investigated the initial ct-scans obtained on admission and findings were not controlled in terms of the exact number of days after symptom onset (15, 26). the retrospective nature of the study might have also introduced selection bias. another major flaw was that in the majority of cases, lab tests and patient outcome were not available. in addition, evaluation of features such as cavitation and pleural effusion requires follow-up. thus, larger multicenter cohorts along with follow-up and complete data are necessary to validate the results. in conclusion, consistent with previous studies, we also determined that covid-19 mainly affects the lower lobes of the lungs. our study also confirmed that ground-glass opacities and consolidation in the lung periphery is the imaging hallmark in covid-19 infection. bronchiectasis, tree-in-bud appearance, discrete pulmonary nodules, cavitation, calcifications, reversed halosign and pleural effusions were uncommon findings. conclusively, recognition of this pattern of chest involvement, in the proper clinical setting, is highly suggestive of covid-19 infection. furthermore, the association observed between dyspnea and extensive ggo on imaging might indicate that presentation with dyspnea is associated with worse prognosis compared to cough and fever. this finding could help medical staff with limited healthcare resources to predict cases with a possible worse outcome when triaging patients. overall, imaging is valuable not only for early suspicion of the disease, but also for follow-up and evaluation of disease severity; however, further investigations are needed to shed light on the radio-clinical correlation of this disease. 5. declarations 5.1. acknowledgements the authors wish to thank dr. nasrin boroumandnia, phd, for providing statistical assistance. 5.2. author contribution s.h. conceived the original idea and supervised the study. n.k. conducted the analysis and drafted the manuscript. s.h., m.b., and m.s. contributed to data collection and performed critical revision. y.m participated in data collection. all authors read and approved the final version of this manuscript. authors orcids sara haseli: 0000-0003-0300-5491 nastaran khalili: 0000-0001-8078-3591 mehrdad bakhshayeshkaram: 0000-0003-4864-6161 morteza sanei-taheri: 0000-0002-8881-9058 yashar moharramzad: 0000-0002-5986-3754 5.3. funding/support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 5.4. conflict of interest none. references 1. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. 2020;395(10223):497-506. 2. coronavirus disease (covid-19) outbreak [available from: https://www.who.int/ westernpacific /emergencies/ covid-19. 3. yang y, yang m, shen c, wang f, yuan j, li j, et al. laboratory diagnosis and monitoring the viral shedding of 2019-ncov infections. 2020. 4. ng m-y, lee ey, yang j, yang f, li x, wang h, et al. imaging profile of the covid-19 infection: radiologic findings and literature review. 2020;2(1):e200034. 5. mahdavi a, khalili n, davarpanah ah, faghihi t, mahdavi a, haseli s, et al. radiologic management of covid19: preliminary experience of the iranian society of radiology covid-19 consultant group (isrcc). 2020(in press). 6. davarpanah ah, mahdavi a, sabri a, langroudi tf, kahkouee s, haseli s, et al. novel screening and triage strategy in iran during deadly coronavirus disease 2019 (covid-19) epidemic: value of humanitarian teleconsultation service. journal of the american college of radiology. 2020. 7. kanne jp, little bp, chung jh, elicker bm, ketai lhjr. essentials for radiologists on covid-19: an update– radiology scientific expert panel. 2020:200527. 8. wynants l, van calster b, bonten mm, collins gs, debray tp, de vos m, et al. systematic review and critical appraisal of prediction models for diagnosis and prognosis of covid-19 infection. 2020:2020.03.24.20041020. 9. song f, shi n, shan f, zhang z, shen j, lu h, et al. emerging 2019 novel coronavirus (2019-ncov ) pneumonia. radiology. 2020;295(1):210-7. 10. shi h, han x, jiang n, cao y, alwalid o, gu j, et al. radiological findings from 81 patients with covid-19 pneumonia in wuhan, china: a descriptive study. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haseli et al. 6 11. yang r, li x, liu h, zhen y, zhang x, xiong q, et al. chest ct severity score: an imaging tool for assessing severe covid-19. 2020;2(2):e200047. 12. zhao w, zhong z, xie x, yu q, liu jjajor. relation between chest ct findings and clinical conditions of coronavirus disease (covid-19) pneumonia: a multicenter study. 2020:1-6. 13. inui s, fujikawa a, jitsu m, kunishima n, watanabe s, suzuki y, et al. chest ct findings in cases from the cruise ship âăijdiamond princessâăi̇ with coronavirus disease 2019 (covid-19). 2020;2(2):e200110. 14. chung m, bernheim a, mei x, zhang n, huang m, zeng x, et al. ct imaging features of 2019 novel coronavirus (2019-ncov ). 2020:200230. 15. pan f, ye t, sun p, gui s, liang b, li l, et al. time course of lung changes on chest ct during recovery from 2019 novel coronavirus (covid-19) pneumonia. 2020:200370. 16. wang l-s, wang y-r, ye d-w, liu q-qjijoaa. a review of the 2019 novel coronavirus (covid-19) based on current evidence. 2020:105948. 17. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. 2020;395(10223):507-13. 18. bernheim a, mei x, huang m, yang y, fayad za, zhang n, et al. chest ct findings in coronavirus disease-19 (covid-19): relationship to duration of infection. radiology. 2020:200463. 19. kong w, agarwal ppjrci. chest imaging appearance of covid-19 infection. 2020;2(1):e200028. 20. kim h. outbreak of novel coronavirus (covid-19): what is the role of radiologists? : springer; 2020. 21. kanne jjr. chest ct findings found in 2019-ncov infections from wuhan, china: what is currently known. 2020. 22. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. 2020. 23. song c-y, xu j, he j-q, lu y-qjm. covid-19 early warning score: a multi-parameter screening tool to identify highly suspected patients. 2020. 24. yuan m, yin w, tao z, tan w, hu yjpo. association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in wuhan, china. 2020;15(3):e0230548. 25. lu j, hu s, fan r, liu z, yin x, wang q, et al. acp risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (covid-19) during the early stage of outbreak in wuhan, china. 2020. 26. wang y, dong c, hu y, li c, ren q, zhang x, et al. temporal changes of ct findings in 90 patients with covid-19 pneumonia: a longitudinal study.0(0):200843. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion declarations references archives of academic emergency medicine. 2019; 7 (1): e35 or i g i n a l re s e a rc h early intubation vs. supportive care outcomes in patients with severe chest trauma; a randomized trial study mohammad nasr-esfahani1, amir bahador boroumand2∗, mohsen kolahdouzan3 1. department of emergency medicine, school of medicine, isfahan university of medical sciences, isfahan, iran. 2. department of emergency medicine, school of medicine, isfahan university of medical sciences, isfahan, iran. 3. department of surgery, faculty of medicine, isfahan university of medical sciences, isfahan, iran. received: march 2019; accepted: may 2019; published online: 9 july 2019 abstract: introduction: early intubation is one of the critical issues in patients with chest trauma. this study aimed to examine the effect of early intubation on outcomes of patients with severe blunt chest trauma. methods: this clinical trial was performed on patients with blunt chest trauma referring to emergency department. patients were randomly divided to intervention (early intubation) and control (supportive care) groups and the duration of hospitalization, complete recovery rate, laboratory changes, and in hospital mortality were compared between the two groups. results: 64 cases were divided into two equal groups of early intubation and control. there were no significant differences between two groups regarding age (p=0.36), sex (p=0.26), type of trauma (p>0.05), and comorbid diseases (p>0.05). the duration of hospitalization in the early intubation group was significantly lower than that of the control group (p = 0.01). 90.6% of those in early intubation group and 68.8% of those in the control group showed complete recovery (p = 0.03). there was no case of mortality in either group. there was a significant difference in venous blood ph between the groups at 6, 12, 18 and 24 hours after intubation (p < 0.05). also, there was a significant difference in the hco3 level at 6 and 12 hours after intubation (p <0.05). conclusion: early intubation is better than supportive treatment in patients with severe chest trauma because of a better complete recovery rate, lower duration of hospitalization, and better acid/base situation. keywords: intubation; wounds and injuries; thorax; hospitalization; multiple trauma cite this article as: nasr-esfahani m, boroumand a b, kolahdouzan m. early intubation vs. supportive care outcomes in patients with severe chest trauma; a randomized trial study. arch acad emerg med. 2019; 7(1): e35. 1. introduction severe blunt chest trauma may causes rupture of the lung tissue, pulmonary contusion, intra-parenchymal hemorrhage, and alveolar collapse (1). examination of chest injuries at the capillary level has shown that pulmonary contusion can lead to lung edema, alveolar edema, and even severe perivascular edema, resulting in the activation of inflammatory mediators, each of which causes lung tissue edema and inappropriate function of vascular permeability and changes in surfactant, even in areas that have not been traumatized (13). airway management is one of the first and most important principles of saving the lives of traumatic individuals, which should be done properly in people who are ex∗corresponding author: amir bahador boroumand, school of medicine, isfahan university of medical sciences, isfahan, iran; email: abbg68@yahoo.com; tel:+989359847673 pected to have a respiratory problem (4). failure to protect the airway is the most important cause of preventable mortality after a traumatic event (5). the most important ways of protecting the respiratory tract are laryngoscopy and endotracheal intubation, which are the most reliable, safe and most commonly used methods for facilitating ventilation (6). depending on the severity of chest trauma, 50-70% of people develop respiratory failure (7), and they need to be intubated. given the importance of intubation in trauma patients, in 2002 the eastern association for the surgery of trauma (east) has defined indications for immediate intubation in traumatic individuals. these indications include: airway obstruction, reduced respiratory rate, severe hypoxemia, decreased consciousness and severe brain injury (glasgow coma scale (gcs) ≤ 8), cardiac arrest, and severe hemorrhagic shock (8, 9). such indications are known as early and late indications of intubation. but, some of the intubations that can be performed shortly after the trauma based on the decision of the physician, or for other reasons indicathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr-esfahani et al. 2 tive of the patient’s need for intubation. such indications, usually include damage to the face, changes in the level of consciousness, difficulty breathing, respiratory distress, intoxication, and preoperative control (8). a study by trupka et al. showed that early intubation of trauma patients within 2 hours after injury is a useful and safe method that is capable of reducing post-traumatic organ failure and improving outcome (10). but, sise et al. found no significant difference between the patients who underwent early intubation and the control group regarding the rate of hypotension, bradycardia, and aspiration (8). considering the contradictory results presented in the studies and the importance of preserving airways in patients with chest trauma and pulmonary damage, this study aimed to compare the outcomes of early intubation versus supportive care in management of patients with severe blunt chest trauma. 2. methods 2.1. study design and setting this randomized clinical trial was performed on patients with multiple traumatic injuries referring to emergency department (level i) of al-zahra and kashani hospitals, isfahan. iran, from jan 2016 to dec 2018. the methodology of this research was approved by ethics committee of isfahan university of medical sciences (code=ir.mui.rec.1397.074). this study is registered in iranian registry of clinical trials database with irct20130311012782n31 code. 2.2. participants all adult (age > 18 years) multiple trauma patients with a trauma severity score of ≥ 5 based on thoracic trauma severity (tts) scoring system, with informed consent and agreement for participating were included. patients who needed rapid-sequence intubation (less than 6 minutes after entering the emergency room), including severe head trauma patients with gcs ≤8, patients with respiratory distress with respiratory rate less than 9 and/or more than 30, airway obstruction, severe hypoxemia, cardiac arrhythmias, and severe hemorrhagic shock, as well as burns of more than 40%, severe burns of the face, oropharynx and trachea, and airway obstruction were not enrolled in the study. 2.3. intervention after the initial evaluation, clinical examination, and critical consideration by an emergency phycision, eligible patients undewent portable chest radiology, and the patients’ trauma severity scores were calculated using tts system (11). then patients were randomly divided into two parallel groups of early intubation (intervention) or supportive care (control) using random allocation software (block randomization method). after full respiratory and cardiac monfigure 1: flow diagram of patients enrollment. itoring, early intubation cases underwent endotracheal intubation using rapid sequence intubation method. all intervention subjects were ventilated using synchronized intermittent mechanical ventilation (simv ) mode, 8cc per kilogram tidal volume, 100% fio2, and 12 times respiration per minute. patients were extubated after one day (24 hours) of intubation, if they did not have the necessary contraindications. control group underwent routine supportive care such as, oxygen therapy with oxygen mask (100% oxygen with 8 to 10 liters per minute flow), head and neck positioning, pulse oximetry, and full respiratory and cardiac monitoring. both groups received midazolam and fentanyl for relaxation and pain relief. all patients were managed by a senior emergency medicine resident under direct supervision of an emergency medicine specialist. 2.4. data gathering demographic data, type of trauma, need for blood transfusion, and trauma severity based on tts were recorded for all patients. venous blood gas analysis (ph, hco3, pco2, pao2), vital signs (systolic blood pressure, diastolic blood pressure, pulse rate, temperature), hemoglobin (hb), and blood sugar (bs) were measured and recorded every three hours until six hours after entering the emergency room and then every 6 hours (for 24 hours in total) for both group. 2.5. outcomes the duration of hospitalization (from admission to discharge from surgery department), complete recovery rate, laboratory and hemodynamic changes, and in hospital mortality were considered as measured outcomes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e35 table 1: baseline characteristics of patients in early intubation and supportive care groups variable early intubation control p age mean ± sd 42.03±16.76 45.28±19.36 0.36 sex male 21 (65.6) 25 (78.1) 0.26 female 11 (34.4) 7 (21.9) comorbid disease diabetes 7 (21.9) 6 (18.8) 0.75 hypertension 12 (37.5) 7 (21.9) 0.17 type of trauma bone fracture 25 (75.1) 22 (68.8) 0.57 pneumothorax 23 (74.2) 21 (65.6) 0.45 hemothorax 14 (43.8) 12 (37.5) 0.61 free intra-abdominal fluid 5 (15.6) 4 (12.5) 0.71 trauma severity tts score 7.53±1.66 7.18±1.53 0.56 data are presented as mean ± standard deviation (sd) or frequency (%). tts: thoracic trauma severity. table 2: outcomes of patients in early intubation and supportive care groups outcome early intubation control p duration of hospitalization 5.18±1.33 9.43±2.25 0.01 complete recovery 29 (90.6) 22 (68.8) 0.03 recovery with complications 3 (9.4) 10 (31.3) 0.01 data are presented as frequency (%). 2.6. statistical analysis considering 80% power and 95% confidence interval (ci), and the precision of estimation of 7% for standard deviation, minimum sample size was calculated to be 32 cases per group. data were analyzed using spss version 20 software. quantitative data were presented as mean and standard deviation, and qualitative data were indicated as percentage and frequency. chi-square test was used to compare quantitative data between the groups. independent t-test was used to compare the qualitative data between the groups. also, repeated measures anova was used to compare the changes in quantitative data at different times. a p-value less than 0.05 was considered as significant. 3. results 3.1. baseline characteristics of studied patients 64 cases were divided into two equal groups of early intubation and control (figure 1). table 1 compares the baseline characteristics of the studied patients. there were no significant differences between the two groups regarding age (p=0.36), sex (p=0.26), type of trauma (p>0.05), and comorbid diseases (p>0.05). 3.2. outcomes tables 2 and 3 compare the studied outcomes between groups. the duration of hospitalization in the early intubation group was significantly lower than that of the control group (p = 0.01). 90.6% of those in the early intubation group and 68.8% of those in control group showed complete recovery (p = 0.03). there was no case of mortality in either group. there was a significant difference in venous blood ph between the groups at 6, 12, 18 and 24 hours after intubation. also, there was a significant difference in the hco3 level at 6 and 12 hours after intubation (p <0.05). 4. discussion based on the findings of this study, use of early intubation for patients with severe blunt trauma results in lower duration of hospitalization and better acid/base balances without any hemodynamic and laboratory impairment. recent studies have focused more on protecting the patient and using less risky methods in patients who do not have a clear indication for early intubation, while few studies have been done to discuss early intubation. a study done by sise and colleagues examined the indications for early intubation to evaluate the incidence and outcomes in 1,000 consecutive patients. they indicated that early intubation indications might change depending on the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr-esfahani et al. 4 table 3: venous blood gas analysis, vital signs, glucose and hemoglobin changes among patients in early intubation and supportive care groups variable early intubation control p ph on arrival 7.30±0.09 7.18±0.13 0.21 3h 7.25±0.06 7.17±0.10 0.05 6h 7.38±0.09 7.23±0.17 0.006 12h 7.39±0.10 7.29±0.16 0.05 18h 7.40±0.07 7.36±0.15 0.009 24h 7.38±0.06 7.34±0.18 >0.001 hco3 on arrival 23.63±5.54 18.42±8.86 0.18 3 22.41±7.53 18.23±7.03 0.68 6h 23.80±3.46 21.34±7.91 >0.001 12h 24.76±3.18 26.21±8.19 >0.001 18h 25.32±5.76 26.89±7.51 0.17 24h 24.70±6.18 26.02±7.27 0.34 pco2 on arrival 50.05±16.73 47.41±19.17 0.76 3h 51.16±20.02 49.21±19.87 0.95 6h 49.18±13.52 40.49±9.14 0.02 12h 52.60v13.10 42.04±12.71 0.46 18h 45.90±9.78 42.69±10.25 0.57 24h 44.34±8.87 41.01±11.59 0.27 systolic blood pressure (mmhg) on arrival 131.51±24.94 115.25±31.56 0.16 6h 120.96±18.89 116.25±24.66 0.58 12h 123.84±18.98 117.35±18.37 0.62 24h 130.43±18.36 122.01±21.84 0.62 diastolic blood pressure (mmhg) on arrival 79.16±15.61 68.18±20.15 0.14 6h 77.40±13.53 70.21±14.08 0.84 12h 77.56±11.80 71.48±15.28 0.32 24h 81.20±11.24 75.76±14.32 0.35 pulse rate (/minutes) on arrival 89.22âś19.58 95.78±18.60 0.79 6h 88.06±15.16 93.37±22.03 0.14 12h 92.75±15.71 93.03±22.14 0.09 24h 89.06±13.79 91.61±19.02 0.10 temperature (c) on arrival 37.12±0.48 37.09±0.57 0.74 6h 37.27±0.50 37.05±0.33 0.18 12h 37.32±0.47 37.20±0.47 0.42 24h 37.21±0.34 37.27±0.53 0.25 blood sugar (mg/dl) on arrival 147.32±77.98 159.43±61.49 0.71 24h 163.38±112.76 167.31±115.29 0.70 hemoglobin (mg/dl) on arrival 12.87±2.24 15.70±7.31 0.30 24h 14.20±5.81 13.59±2.18 0.28 surgeon’s view, and also no significant difference was found between the patients who underwent intubation and the control group for hypotension, bradycardia, trauma during intubation, and aspiration (8). the results of this study, which had a large sample size, are similar to our study as they considered early intubation to be practical and useful. another study by trupka et al showed that early intubation of injured patients within 2 h after trauma is a useful and safe method that is capable of reducing post-traumatic organ failure and improving outcome (10). as indicated by studies, one of the indications that affect early intubation, which is mostly dependent on the physician’s opinion, is the patient’s severe pain. it has been shown that early intubation of the patient due to severe pain can this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e35 improve hospitalization outcomes and reduce postoperative complications (12). this factor can be controlled by administering appropriate analgesics to patients with trauma. in another study, among 120 intubated cases, half of them received strong painkillers, resulting in 3% of patients being subjected to intubation due to severe pain (13). the probability of developing respiratory infections after intubation or ventilator-associated pneumonia (vap) is another issue that is considered about early intubations. however, our study did not indicate the incidence of this problem. evans et al. (14) also examined prehospital intubation of patients with trauma and showed that early intubation was not associated with an increased risk of vap. also in a review article, rapid intubation was recommed for traumatic patients (15). the rate of on arrival pco2 is critical in traumatic patients and explicitly affects the outcome of patients (16). another study assessed 890 intubated patients and found that on arrival hypercapnia and hypocapnia worsen the results of hospitalization in those who are intubated (17). of course, this study examined patients with head trauma, but, we can conclude that early intubation can be beneficial and lead to better regulation of blood gases and blood pco2 in comparison with control group. early intubation of trauma patients, based on the physician’s opinion, is preferable to supportive care as it led to shorter hospitalization time, better recovery, and better vbg results. 5. limitation the study limitations were small sample size and short duration of subsequent follow-up. it could nonetheless be used as a guide for other studies with larger sample sizes and humanfinancial resources. 6. conclusion based on the findings of this study, the use of early intubation for patients with severe blunt trauma results in lower duration of hospitalization and better acid/base balances without any hemodynamic and laboratory impairment. 7. appendix 7.1. acknowledgements we would like to thank dr. keyvan ghadimi for helping us carry out this study. 7.2. author contribution all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors orcids mohammad nasr-esfahani: 0000-0002-5496-9170 amir bahador boroumand: 0000-0001-5055-6881 mohsen kolahdouzan: 0000-0002-3095-6471 7.3. funding/support none. 7.4. conflict of interest none. references 1. ruchholtz s, waydhas c, ose c, lewan u, nast-kolb d, society wgomtotgt. prehospital intubation in severe thoracic trauma without respiratory insufficiency: a matched-pair analysis based on the trauma registry of the german trauma society. journal of trauma and acute care surgery. 2002;52(5):879-86. 2. nelson l. ventilatory support of the trauma patient with pulmonary contusion. respiratory care clinics of north america. 1996;2(3):425-47. 3. matthay ma, ware lb, zimmerman ga. the acute respiratory distress syndrome. the journal of clinical investigation. 2012;122(8):2731-40. 4. moore f, moore e, sauaia a. postinjury multiple organ failure. trauma: mcgraw-hill new york; 2004. p. 1397423. 5. ivatury rr, guilford k, malhotra ak, duane t, aboutanos m, martin n. patient safety in trauma: maximal impact management errors at a level i trauma center. journal of trauma and acute care surgery. 2008;64(2):265-72. 6. bouderka ma, fakhir b, bouaggad a, hmamouchi b, hamoudi d, harti a. early tracheostomy versus prolonged endotracheal intubation in severe head injury. journal of trauma and acute care surgery. 2004;57(2):251-4. 7. nast-kolb d, trupka a, waydhas c. early intubation in trauma patients. the integrated approach to trauma care: springer; 1995. p. 40-51. 8. sise mj, shackford sr, sise cb, sack di, paci gm, yale rs, et al. early intubation in the management of trauma patients: indications and outcomes in 1,000 consecutive patients. journal of trauma and acute care surgery. 2009;66(1):32-40. 9. dunham mc, barraco rd, clark de, daley bj, davis iii fe, gibbs ma, et al. guidelines for emergency tracheal intubation immediately after traumatic injury. journal of trauma and acute care surgery. 2003;55(1):162-79. 10. trupka a, waydhas c, nast-kolb d, schweiberer l. early intubation in severely injured patients. european journal of emergency medicine: official journal of the european society for emergency medicine. 1994;1(1):1-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. nasr-esfahani et al. 6 11. pape h-c, remmers d, rice j, ebisch m, krettek c, tscherne h. appraisal of early evaluation of blunt chest trauma: development of a standardized scoring system for initial clinical decision making. journal of trauma and acute care surgery. 2000;49(3):496-504. 12. hedderich r, ness tj. analgesia for trauma and burns. critical care clinics. 1999;15(1):167-84. 13. chao a, huang c-h, pryor jp, reilly pm, schwab cw. analgesic use in intubated patients during acute resuscitation. journal of trauma and acute care surgery. 2006;60(3):579-82. 14. evans hl, zonies dh, warner kj, bulger em, sharar sr, maier rv, et al. timing of intubation and ventilatorassociated pneumonia following injury. archives of surgery. 2010;145(11):1041-6. 15. mayglothling j, duane tm, gibbs m, mccunn m, legome e, eastman al, et al. emergency tracheal intubation immediately following traumatic injury: an eastern association for the surgery of trauma practice management guideline. journal of trauma and acute care surgery. 2012;73(5):s333-s40. 16. thomas sh, orf j, wedel sk, conn ak. hyperventilation in traumatic brain injury patients: inconsistency between consensus guidelines and clinical practice. journal of trauma and acute care surgery. 2002;52(1):47-53. 17. davis dp, idris ah, sise mj, kennedy f, eastman ab, velky t, et al. early ventilation and outcome in patients with moderate to severe traumatic brain injury. critical care medicine. 2006;34(4):1202-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e35 rev i ew art i c l e prevalence of underlying diseases in hospitalized patients with covid-19: a systematic review and metaanalysis amir emami1∗, fatemeh javanmardi1, neda pirbonyeh1, ali akbari2 1. microbiology department, burn and wound healing research center, shiraz university of medical sciences, shiraz, iran. 2. department of anesthesiology, school of medicine, shiraz university of medical sciences, shiraz, iran. received: march 2020; accepted: march 2020; published online: 24 march 2020 abstract: introduction: in the beginning of 2020, an unexpected outbreak due to a new corona virus made the headlines all over the world. exponential growth in the number of those affected makes this virus such a threat. the current meta-analysis aimed to estimate the prevalence of underlying disorders in hospitalized covid-19 patients. methods: a comprehensive systematic search was performed on pubmed, scopus, web of science, and google scholar, to find articles published until 15 february 2020. all relevant articles that reported clinical characteristics and epidemiological information of hospitalized covid-19 patients were included in the analysis. results: the data of 76993 patients presented in 10 articles were included in this study. according to the metaanalysis, the pooled prevalence of hypertension, cardiovascular disease, smoking history and diabetes in people infected with sars-cov-2 were estimated as 16.37% (95%ci: 10.15%-23.65%), 12.11% (95%ci 4.40%-22.75%), 7.63% (95%ci 3.83%-12.43%) and 7.87% (95%ci 6.57%-9.28%), respectively. conclusion: according to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, chronic obstructive pulmonary disease (copd), malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized covid-19 patients, respectively. keywords: comorbidity; covid-19; severe acute respiratory syndrome coronavirus 2; meta-analysis cite this article as: emami a, javanmardi f, pirbonyeh n, akbari a. prevalence of underlying diseases in hospitalized patients with covid19: a systematic review and meta-analysis. arch acad emerg mede. 2020; 8(1): e35. 1. introduction in late 2019, a novel corona virus (first: 2019-ncov, then: sars-cov-2) was identified as the cause of a cluster of pneumonia cases, which infected a lot of people in wuhan, a city in the hubei province of china (1). sars-cov-2 rapidly spread and led to an outbreak in china and then became a global health emergency. although control measures and isolations have been applied for prevention, the infection has increased and caused a pandemic (2). although this virus belongs to a relatively well-known viral family, coronaviridae, and is similar to viruses that caused severe acute respiratory syndrome (sars), which had an outbreak in 2002, and middle east respiratory syndrome (mers), which had ∗corresponding author: amir emami; microbiology department, burn and wound healing research center, shiraz university of medical sciences, shiraz, iran. email: emami.microbia@gmail.com, tel: +98-71-3230 5884 an outbreak in 2012, in some characteristics, there are a lot of uncertainties and unknown specifications about this virus such as its origin and source of infection, its emergence, and its mechanism of action and transmission (3, 4). since the number of covid-2019 cases is rising around the world and it has been associated with a large number of mortality and morbidity, it has led to a new global phobia called coro phobia (5). based on recent reports, the novel corona virus can be identified through various symptoms (fever, cough, dyspnea, myalgia, and fatigue) (6-8). similar to other viral respiratory infections, sars-cov-2 or covid-19 can be transmitted through the respiratory tract. it mainly causes respiratory tract infections and develops severe pneumonia in infected patients who may require intensive care. severe disease may result in death due to progressive respiratory failure (9, 10). everyone is susceptible to this virus, but the elderly and those with underlying diseases are more at risk of adverse outcomes. current knowledge has shown that death rate is high in people with chronic underlythis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 2 ing diseases (11). therefore, special attention should be paid to the elderly and immunocompromised patients. infections might progress rapidly in these groups and timely clinical decisions are needed (12). currently, information on the prevalence of predominant chronic diseases is rare. moreover, knowing the underlying diseases in covid-19 infected patients is important for healthcare workers. in the current study, a systematic review and meta-analysis was conducted on the prevalence of underlying diseases in confirmed hospitalized covid-19 cases. 2. methods 2.1. search strategy in order to find relevant studies, international databases including pubmed, scopus, web of science, google scholar, and embase were searched for articles published until 16 february 2020. the following search terms were used (designed using english mesh keywords and emtree terms): [sars-cov-2 and characteristics] or , [2019-ncov and characteristics]" or "covid-19 and comorbidities] or [new coronavirus and characteristics and comorbidities] or [wuhan coronavirus and characteristics and comorbidities] or [coronavirus and characteristics and comorbidities]. additionally, extra searches were performed in the reference lists of included studies to avoid missing papers. moreover centers for disease control and prevention (cdc) and world health organization (who) portals as the national public health institute were evaluated. due to the huge number of articles in chinese language, the abstracts were evaluated in these studies. 2.2. inclusion and exclusion criteria any relevant articles that reported clinical characteristics and epidemiological information on infected patients were included in the analysis. all articles with any design (randomized controlled trials, non-randomized controlled trials, case-control studies, cross-sectional studies) were included. articles were excluded if appropriate information was not reported. 2.3. data extraction and paper quality evaluation two authors (a.e. and f.j.) screened and evaluated the literature independently. all the included papers were assessed using the newcastle-ottawa scale and the results are provided in table 1 (13). the following features were extracted for pooled estimation: name of the first authors and age, sex, and coexisting condition of the patients. 2.4. statistical analysis overall prevalence with 95% confidence interval was estimated via inverse variance method. heterogeneity was evaluated using chi-square and i2. the random effect model was used in case of considerable heterogeneity, which was defined as i2>75%. sensitivity analysis was done according to outlier data. egger’s regression test was used to evaluate publication biases. all statistical analyses were performed using stata 13, metaprop command. 3. results 3.1. characteristics of included studies in the initial search, 1250 articles were found in different databases. all papers were screened by reading their abstracts and 289 of them were eliminated due to being duplicates found in different databases. after evaluating the full texts, 804 studies were excluded due to presenting data that were irrelevant to our aim. 10 articles met the inclusion criteria but some of the required information was not reported in all of the articles. figure1 shows the search details, and the characteristics of included studies are provided in table 2. finally, the available data of 3,403 hospitalized patients with covid-19 infection were used for the analysis. 3.2. prevalence of underlying diseases in hospitalized covid-19 cases hypertension through the current meta-analysis, it was found that hypertension is the most prevalent underlying disease in hospitalized covid-19 cases. 16% (95%: ci: 10.15%-23.65%) of sarscov-2 infected cases were hypertensive (figure 2). this information was reported in 7 studies. according to the i2 index, which was calculated to be 86.42%, and the chi-square results, there was high and significant heterogeneity between the studies (p<0.001). no publication bias was found in studies (t= -1.67, p=0.15). in addition, the corresponding funnel plot is provided in figure 3. cardiovascular disease in order to estimate the pooled prevalence of cardiovascular disease in covid-19 patients, 8 studies were evaluated. the incidence was 12.11% (95%ci: 4.40% – 22.75%), with high and significant heterogeneity (i2=95.89%), also no publication bias was present according to eggers’s test (t= 1.99, p=0.09). the funnel plot has been shown in figure 3. sensitivity analysis did not show significant changes. smoking in the forest plot drawn (figure 4), the pooled prevalence of sars-cov-2 infection in hospitalized patients with history of smoking was estimated as 7.63 percent. high and significant heterogeneity was found between the 6 included studies (i2= this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e35 90.19%, p < 0.001). moreover, no publication bias was found (t= -0.24, p=0.82). it is worth noting that the number of smokers in wenhua liang’s study was calculated using the information presented in the study (14). diabetes mellitus using the data of 6 included articles, the prevalence of diabetes among people who were infected with sars-cov-2 was estimated to be 7.87% (95%ci: 6.57% âăş 9.28%), which is presented in figure 5. no publication bias was present based on egger’s test and the funnel plot presented in figure 3 (t=-1.64, p=0.17). chronic kidney disease as shown in figure 6, the pooled prevalence of acute kidney diseases in sars-cov-2 hospitalized patients was estimated as 0.83% (95% ci: 0.37%1.43%). a fixed model was used for meta-analysis of data presented in 7 included studies. no publication bias was present according to egger’s test and the related funnel plot presented in figure 3 (t=1.83, p=0.12) malignancy the pooled prevalence of malignancy among hospitalized covid-19 patients was estimated to be 0.92% (95% ci: 0.56%-1.34%) (results presented in 7 articles, figure 7). in this section, a fixed effect analysis was used. the value of t in egger’s test was 1.14 and the p-value was 0.305, which means that no publication bias was present. the related funnel plot is depicted in figure 3. chronic obstructive pulmonary diseases (copd) the last comorbidity that was studied using the included articles was chronic obstructive pulmonary diseases (copd). according to our statistical analysis, the incidence rate of copd in hospitalized covid-19 patients was 0.95% (95% ci: 0.43%-1.61%). although there were many articles about this new coronavirus, this coexisting disorder was reported in only 5 published studies. in order to evaluate the pooled prevalence, a fixed model was used and the results are shown in figure 8. the value of t in egger’s test was found to be 1.81 and the p-value was 0.16, which means that no publication bias was present. the related funnel plot is shown in figure 3. 4. discussion china and the rest of the world have faced an outbreak of a novel corona virus. the widespread distribution of this virus has led to a major concern, globally. human coronaviruses are among the pathogens causing viral respiratory infections, and the recently detected strain called sars-cov2 has caused a big challenge for countries all over the world (15, 16). this is the third contagious coronavirus leading to an epidemic in the 21st century after mers and sars (17). the key problems surrounding this novel virus are as follows: diagnosis, mode of transmission, long incubation period (3 to 14 days), predicting the number of infected cases in the community, and insufficient protection resources due to its pandemic specification (15, 18). the accurate transmission rate of sars-cov-2 is unknown, since various factors impact its transmission. moreover, infection of family clusters and healthcare workers indicate the human to human transmission of the disease and its contagiousness, which makes the condition more complicated (19, 20). since sars-cov-2 is a newly identified pathogen, there is no pre-existing immunity to it in the human community, also there is no definitive cure to interrupt or reduce its astonishing spread. these ambiguities make the condition more serious for vulnerable members of the community, which include individuals with immune problems, co-existing comorbidity and elderly people. despite the novelty of the topic, there are a lot of proposed studies about history, transmission route, urgency of responding, pathogenic potential characteristics and prevention strategies but there are still some underlying diseases that have remained unknown (21). according to the current analysis, hypertension, cardiovascular diseases, diabetes, kidney disease, smoking, and copds were among the most prevalent underlying diseases among hospitalized patients with covid-19. in terms of pre-existing medical conditions, cardiovascular diseases had the highest prevalence among diseases that put patients at higher risk of sars-cov-2 threats. decreasing the proinflammatory cytokines, which leads to a weaker immune function may account for this condition (2, 22). it is worth noting that similar results were found regarding mers (23). we also found that smokers are more susceptible to coronavirus infections, especially to the most recent species. various reasons may justify this happening. it has been mentioned that smokers have unregulated ace2 in remodeled cell types, which is consistent with results of sars studies. however, factors such as amount of smoking, the duration of smoking, and the duration of smoking cessation also play a role. in some previous studies on mers-cov-2 it has been shown that dipeptidyl peptidase iv (dpp4), which is the specific receptor for this virus, had a higher rate of expression in smokers and copd patients (24). although the results of the current analysis indicate that smoking can be an underlying factor that makes people susceptible to covid-19 complications, in some studies, especially covid-19 related studies, no strong evidence has been found regarding the correlation of copd and smoking with being infected with this new virus. but the important point that must be taken into consideration is that the outcome of sars-cov-2 infection is more severe in copd cases and smokers (25). as mentioned in the results section, patients with malignancies are more in danger than those without any tumor. anticancer treatments such as chemotherapy and surgery put this group into an immunosuppressive state and subsequently at higher risk of mers-cov-2 infection (26). among this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 4 those with malignancies, lung cancer patients seems to be more susceptible, and they must follow guidance on restricting any contact with possible infected zones or individuals for their safety (14). possible risk factors for progressive and severe illness may include the above-mentioned factors but are not limited to them; pregnancy and old age are other risky conditions, which should be monitored meticulously. however, there is no clear evidence about the risk of transmission of covid-19 to the newborn during vaginal delivery or transmission via breastfeeding but care and protection of newborns against possible exposure to infection or contaminated conditions such as maternal breast contamination must be observed. since mers-cov-2 is an emerging virus, no specific treatment is currently available (27, 28), and pathophysiology of this condition is still unknown. therefore, general prevention measures such as the following should be followed: washing hands frequently and avoiding touching the eyes, nose, and mouth with contaminated hands, avoiding close contact ,especially with those who have fever, coughing or sneezing, avoiding contact with live animals and consuming raw animal products (29). there are some responsibilities for health policymakers in this critical condition: screening of travelers, triage all patients on admission and immediately isolating all suspected and confirmed cases, providing protective gear, preparing local guidance and instructions for people, especially for high risk groups (30, 31). to the best of our knowledge, this is the first meta-analysis that estimates the prevalence of underlying diseases in patients infected with sars-cov-2. given that most studies on covid-19 are in an early stage, and there are some limitations such as small number of studies, and reports being restricted to china and a few other countries, due to the pandemic nature of the disease, specific patterns should be introduced for different groups, including people with underlying diseases, to minimize the harm. based on the experiences gained on this disease during this short time, a strong recommendation for all people, clinicians, and policymakers is to guide people to protect themselves to avoid being exposed to sars-cov-2, whenever possible (32). another very important advice to patients with underlying diseases during the epidemics like the one caused by the novel virus is to follow guidance on travel restrictions. these groups must be aware of their high-risk situation and comply with all health guidelines such as hand hygiene, face care, and restricting social interactions. in addition, to reduce the morbidity and complications of covid-19 in different populations, especially patients with the mentioned underlying diseases, we recommend clinicians and policymakers to launch diagnostic procedures for such individuals first so that proper treatments can be designed and followed to ensure they are protected within epidemic regions (33). in summary, the results of the current study have shown that in patients with sars-cov-2 infection, hypertension, cardiovascular disease, smoking, and diabetes are the most prevalent co-existing disorders. given that covid-19 has a relatively long incubation period and during this time the infected person can transmit the virus without showing symptoms, it is strongly recommended that patients with chronic or underlying diseases avoid any close contact with other people in the community, especially in epidemic areas. during the current sars-cov-2 pandemic, the statistics reported by different countries regarding associated mortality of those with risk factors, incubation time, and estimated overall mortality have not been consistent and general conclusions should be drawn with caution. it should be noted that the outbreak worsens with decrease in adherence to diagnostic guidelines and prevention strategies, such as avoiding traveling and gathering in public places. 5. conclusion according to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, copd, malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized patients with covid-19, respectively. 6. declarations 6.1. acknowledgements all the authors thank the vice chancellor of research, shiraz university of medical sciences, for their cooperation for obtaining the approval of the ethical committee (code: ir.sums.rec.1398.1379). 6.2. authors contributions a.e designed the study, searched the database, extracted the data and did the quality assessment. f. j did the statistical analysis and wrote the results section, and assessed the quality of studies. a. e and f. j wrote the initial draft and n.p and a.k revised and edited the paper. authors orcids amir emami: 0000-0002-4510-1820 fatemeh javanmardi: 0000-0001-8841-0861 neda pirbonyeh: 0000-0001-5700-3913 ali akbari: 0000-0002-2970-2052 6.3. funding support none. 6.4. conflict of interest all authors declare that they have no conflict of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e35 references 1. tan w, zhao x, ma x, wang w, niu p, xu w, et al. a novel coronavirus genome identified in a cluster of pneumonia cases–wuhan, china 2019– 2020. china cdc weekly. 2020;2(4):61-2. 2. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. 3. gorbalenya ae. 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[zhonghua this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 6 yan ke za zhi] chinese journal of ophthalmology. 2020;56(0):e004. 30. okada p, buathong r, phuygun s, thanadachakul t, parnmen s, wongboot w, et al. early transmission patterns of coronavirus disease 2019 (covid-19) in travellers from wuhan to thailand, january 2020. eurosurveillance. 2020;25(8):2000097. 31. wax rs, christian md. practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov ) patients. canadian journal of anesthesia. 2020. 32. patel a, jernigan db, nco vcdcrt. initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak united states, december 31, 2019-february 4, 2020. mmwr morbidity and mortality weekly report. 2020;69(5):140-6. 33. jin yh, cai l, cheng zs, cheng h, deng t, fan yp, et al. a rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-ncov ) infected pneumonia (standard version). military medical research. 2020;7(1). 34. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 35. wang d, hu b, hu c, zhu f, liu x, zhang j, et al. clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusâăşinfected pneumonia in wuhan, china. jama. 2020. 36. li j, li s, cai y, liu q, li x, zeng z, et al. epidemiological and clinical characteristics of 17 hospitalized patients with 2019 novel coronavirus infections outside wuhan, china. medrxiv. 2020. 37. guan w-j, ni z-y, hu y, liang w-h, ou c-q, he j-x, et al. clinical characteristics of coronavirus disease 2019 in china. new england journal of medicine. 2020. 38. xiao-wei x, xiao-xin w, xian-gao j, kai-jin x, ling-jun y, chun-lian m, et al. clinical findings in a group of patients infected with the 2019 novel coronavirus (sarscov-2) outside of wuhan, china: retrospective case series. bmj: british medical journal (online). 2020;368. 39. wu j, liu j, zhao x, liu c, wang w, wang d, et al. clinical characteristics of imported cases of covid-19 in jiangsu province: a multicenter descriptive study. clinical infectious diseases. 2020. 40. kui l, fang y-y, deng y, liu w, wang m-f, ma j-p, et al. clinical characteristics of novel coronavirus cases in tertiary hospitals in hubei province. chinese medical journal. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e35 table 1: newcastle-ottawa quality assessment scale for cross sectional studies first author, year selection comparability exposure/outcome total score chaolin huang, 2020 ***** * *** ********* nanshan chen,2020 ***** ** *** ********** dawei wang, 2020 ***** ** *** ********** jie.li, 2020 ***** ** *** ********** wei-jie guan, 2020 ***** ** *** ********** xiao-wei xu, 2020 ***** * ** ******** wenhua liang,2020 ***** * *** ********* jin-jin zhang, 2020 ***** ** *** ********** jian wu, 2020 ***** ** *** ********** kui l2020 **** ** *** ********* table 2: characteristics of included studies first author n sex (m/f) age ckd htn dm mal smoking copd cvd chaolin huang, et al. (34) 41 30/11 range: 41-58 3 6 8 1 3 1 6 nanshan chen, et al. (2) 99 67/32 mean: 55.5 ±13.1 3 1 2 40 dawei wang, et al. (35) 138 78/63 median: 56 (42-68) 4 43 14 10 4 20 jie.li, et al. (36) 17 9/8 range: 22-65 8 1 3 wei-jie guan, et al. (37) 1099 640/459 range: 35-58 1 164 81 10 158 12 27 xiao-wei xu, et al. (38) 62 35/27 median: 41 (32-52) 5 1 1 1 wenhua liang,et al. (14) 1590 18 111 jin-jin zhang, et al. (16) 140 71/69 median: 57 (25-87) 2 42 17 9 2 7 jian wu, et al. (39) 80 39/41 mean: 46.1 ± 15.4 1 1 25 kui l, et al. (40) 137 61/76 median: 57(20-83) 13 14 2 10 ckd: chronic kidney disease; htn: hypertension; dm: diabetes mellitus; mal: malignancy; copd: chronic obstructive pulmonary diseases; cvd: cardiovascular disorders. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 8 figure 1: prisma flow chart of the systematic literature review and article identification. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e35 figure 2: prevalence of hypertension among patients hospitalized with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 10 figure 3: funnel plot for meta-analysis of the prevalence of underlying diseases in covid-19 infected cases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e35 figure 4: prevalence of cardiovascular disease among patients hospitalized with covid-19. figure 5: prevalence of smokers among patients hospitalized with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 12 figure 6: prevalence of diabetes among patients hospitalized with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2020; 8(1): e35 figure 7: prevalence of kidney disease among patients hospitalized with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. emami et al. 14 figure 8: prevalence of malignancies among patients hospitalized with covid-19. figure 9: prevalence of chronic obstructive pulmonary disease (copd) among patients hospitalized with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e27 or i g i n a l re s e a rc h electrocardiogram changes as an independent predictive factor of mortality in patients with acute ischemic stroke; a cohort study payman asadi1, seyyed mahdi zia ziabari1∗, donya naghshe jahan1, arezoo jafarian yazdi1 1. road trauma research center, school of medicine guilan university of medical sciences, rasht, iran. received: february 2019; accepted: march 2019; published online: 27 april 2019 abstract: introduction: various factors such as age and severity of the stroke have been deemed connected with risk of mortality in patients with acute ischemic brain stroke. the present study was performed with the aim of evaluating the role of electrocardiogram (ecg) changes in predicting the outcome of these patients. methods: in this cohort study, patients who had presented to the emergency department of a teaching hospital during 1 year and were diagnosed with acute ischemic stroke were evaluated. demographic data and 12-lead ecg findings of the patients were gathered and their relationship with 1-year mortality was analyzed. results: finally, 546 stroke patients with the mean age of 69.5±12.7 (24 – 100) years were studied (53.3% female). 82.7% of the studied patients had at least one of the evaluated ecg abnormalities. the most common ecg findings included normal sinus rhythm (27.3%), inverted t wave (21.2%), sinus tachycardia (11.7%), atrial fibrillation (af) (11.5%), and pathologic q wave (9.9%). in the end, 117 (20.9%) patients died during the 1-year follow-up. frequencies of non-sinus rhythm (p < 0.0001), inverted t wave (p = 0.0001), af rhythm (p<0.0001), pathologic q (p<0.0001), st segment changes (p = 0.011), and atrioventricular (av ) node block (p = 0.007) were significantly higher in patients who died. ecg changes increased the odds of 1-year mortality of these patients 4 times (odds ratio = 4.05 with 95% ci: 2.39 6.87; p < 0.0001). additionally, age over 60 years and having a history of cardiac diseases increased the odds of mortality 6 (95% ci: 1.4 – 27.9) and 1.5 (95% ci: 0.9 – 2.1) times, respectively. conclusion: based on the findings of the present study, it seems that along with age and history of cardiac diseases, ecg changes can be considered as an independent predictive factor of mortality in patients with ischemic stroke. keywords: stroke; brain ischemia; patient outcome assessment; electrocardiography; prognosis; emergency service, hospital cite this article as: asadi p, zia ziabari s m, naghshe jahan d, jafarian yazdi a. electrocardiogram changes as an independent predictive factor of mortality in patients with acute ischemic stroke; a cohort study. arch acad emerg med. 2019; 7(1): e27. 1. introduction stroke is one of the important causes of mortality and dysfunction, and can affect the quality of life of both patients and their relatives (1, 2). it is estimated that in the united states about 57.9 billion dollars is spent on stroke and its consequences each year (3). every year, 5 million people die following stroke all over the world and at least one sixth of those who survive will have another stroke in the 5 following years. two third of stroke cases happen in developing countries and 80% of all mortalities due to stroke also hap∗corresponding author: seyyed mahdi zia ziabari; emergency department, poursina hospital, rasht, guilan. tel: 00989111375056 email: smzz102186@gmail.com pen in these countries (4). various factors such as age and severity of the stroke have been deemed connected with risk of mortality in these patients (5). electrocardiography plays an important role in detecting a number of risk factor predicting stroke such as atrial fibrillation and left ventricular hypertrophy, which are components of framingham stroke risk profile (6). on the other hand, brain stroke itself and increase in the intracranial pressure can lead to changes in electrocardiogram (ecg) even in the absence of history of cardiac underlying illnesses (7). most common changes in ecg reported in patients with acute ischemic stroke include qt prolongation, t wave abnormalities, atrioventricular (av ) block, prominent u wave, and st segment abnormalities (8, 9). atrial fibrillation (af) has also been commonly reported but most of the times it is not known whether af leads to cardioembolic accidents, or it is secondary to the brain ischemia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. asadi et al. 2 (10). some studies have shown that ecg changes can be considered as predictive factors for brain stroke outcomes and mortality due to it (11-13). however, studies are still ongoing on this subject. therefore, the present study was performed with the aim of evaluating the role of ecg changes in predicting the outcome of patients presenting to the emergency department following acute ischemic stroke. 2. methods 2.1. study design and setting in this cohort study, patients who had presented to the emergency department of poursina hospital, rasht, iran, during 1 year and were diagnosed with acute ischemic stroke were evaluated. demographic data and 12-lead ecg findings of the patients were gathered and their relationship with 1-year outcome of the patients was analyzed. protocol of the study was approved by the ethics committee of guilan university of medical sciences. the researchers adhered to confidentiality of patients’ data. 2.2. participants all the patients presenting to the emergency department with diagnosis of acute ischemic stroke were included without considering any age or sex limitation. patients’ medical profile being unavailable, being lost to follow-up, having history of dysrhythmia, and not giving consent for participation in the study were among the most important exclusion criteria of the study. 2.3. data gathering demographic data, history of underlying illnesses, and the findings of 12-lead ecg were gathered after registration on their clinical profile. diagnosis of ischemic stroke was done based on clinical findings and imaging, by an emergency medicine specialist and a neurologist. in addition, ecgs of all the patients were interpreted by an emergency medicine specialist. ecg changes evaluated in the present study included pathologic q wave, av node block, af rhythm, inverted t wave, st segment changes, left bundle branch block (lbbb), right bundle branch block (rbbb), sinus tachycardia, sinus bradycardia, atrial flutter, sinus arrest, sinus exit block, qt prolongation, and etc. finally, all the patients included in the study were followed for 1 year from the time they were admitted to the emergency department using phone calls and cases with mortality related to brain stroke were recorded. a trained intern was responsible for data gathering and followup of the patients under direct supervision of the emergency medicine attend. 2.4. statistical analysis for analysis of data, spss 20 statistical software was used. the relationship between qualitative variables was evaluated using chi-square and fisher’s exact test and the relationship between quantitative variables was assessed via independent t-test. for multivariate analysis of mortality predictors, logistic regression model and backward lr method were applied. odds ratio of independent factors in prediction of 1year mortality were reported with 95% confidence interval (ci). findings were reported as mean and standard deviation, or frequency and percentage. significance level of the tests was considered to be p < 0.05 in this study. 3. results 3.1. baseline characteristics 600 patients were included in the study, 54 cases were eliminated due to various reasons (36 cases were lost to followup and in 18 cases data were not recorded accurately). finally, 546 stroke patients with the mean age of 69.5±12.7 (24 – 100) years were studied (53.3% female). 36.1% (197 cases) of the participants had a history of cardiac diseases, 63.9% (349 patients) had a history of hypertension, 32.6% (178 participants) had a history of diabetes, and 10.6% (58 cases) were smokers. 82.7% of the studied patients had at least one of the evaluated ecg abnormalities. the most common ecg findings of the studied patients included normal sinus rhythm (27.3%), inverted t wave (21.2%), sinus tachycardia (11.7%), atrial fibrillation (11.5%), and pathologic q wave (9.9%). in the end, 117 (20.9%) patients died during the 1-year followup. 3.2. predictive factors of mortality on average, those who survived were about 10 years younger than those who died (65.9±12.6 versus 75.9±10.2, p<0.0001). in addition, there was a significant correlation between the history of cardiac diseases (p<0.0001) and history of hypertension (p = 0.01) with mortality. but there was no significant correlation between mortality and sex (p = 0.311), having diabetes (p = 0.779), or smoking (p = 0.920). ecg findings of the studied patients based on mortality status have been summarized in table 1. frequencies of non-sinus rhythm (p < 0.0001), inverted t wave (p = 0.0001), af rhythm (p<0.0001), pathologic q (p<0.0001), st segment changes (p = 0.011), and av node block (p = 0.007) were significantly higher in patients who died. the mortality rate of patients with abnormal and normal ecgs was 45.1% and 14.1%, respectively (p = 0.0001; figure 1). this rate was 59.3% in patients with inverted t wave and 73.8% in those with af rhythm. based on the logistic regression model with backward lr method, ecg changes was found to be an independent prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e27 table 1: comparison of ecg findings between ischemic stroke patients who died and those who survived ecg findings died survived p value normal sinus rhythm(nsr) 21 (10.5) 128 (37.0) < 0.001 inverted t wave 59 (29.5) 57 (16.5) < 0.001 sinus tachycardia 26 (13.0) 38 (11.0) 0.480 atrial fibrillation (af) 47 (23.5) 16 (4.6) < 0.001 pathologic q wave 32 (16.0) 22 (6.4) < 0.001 sinus bradycardia 13 (6.5) 26 (7.5) 0.657 poor r wave progression 13 (6.5) 23 (6.6) 0.947 late transition 14 (7.0) 18 (5.2) 0.389 st segment changes 18 (9.0) 13 (3.8) 0.011 left ventricular hypertrophy 13 (6.5) 14 (4.0) 0.203 left anterior superior fascicular block 7 (3.5) 17 (4.9) 0.438 right bundle branch block (rbbb) 10 (5.0) 17 (4.9) 0.964 left bundle branch block (lbbb) 8 (4.0) 10 (2.9) 0.484 left atrial enlargement 5 (2.5) 16 (4.6) 0.214 atrioventricular block 11 (5.5) 5 (1.4) 0.007 qt prolongation 7 (3.5) 6 (1.7) 0.192 other 34 (44.7) 42 (55.3) 0.114 data are presented as frequency (%). figure 1: survival rate of ischemic stroke patients based on presence (green line) or absence (blue line) of normal sinus rhythm. x axis= time (days), y axis: cumulative survival. dictor of mortality in patients with stroke, so that changes in ecg increased the odds of 1-year mortality of these patients 4 times (odds ratio = 4.05 with 95% ci: 2.39 6.87; p < 0.0001). based on this model, age over 60 years and having a history of cardiac diseases also increased the odds of mortality 6 (95% ci: 1.4 – 27.9) and 1.5 (95% ci: 0.9 – 2.1) times, respectively. 4. discussion based on the findings of the present study, it seems that along with age and history of cardiac diseases, changes in ecg can be considered as an independent factor predicting 1-year mortality of the patients with ischemic stroke. occurrence of ecg changes, increases the odds of 1-year mortality of stroke patients about 4 times. in the present study, more than 80% of the patients had at least one change in ecg. christensen et al. reported the rate of changes in ecg among patients with ischemic brain stroke to be about 60% (12). koochaki et al. also reported the prevalence of ecg changes in patients with ischemic stroke to be 68.3% (14). in 2010, van bree et al. expressed that 81% of their studied patients in netherlands had at least one abnormality in their ecg (15). overall, considering the results of the present study and other studies, it can be concluded that ecg changes are very common among patients with stroke. in the present study, the most common changes in ecgs of the patients were inverted t wave, af rhythm, and pathologic q wave, respectively. in different studies, findings regarding the most common ecg changes observed vary. in the study by koochaki et al. inverted t wave and st segment elevation/depression were the most common changes observed in ecg of the patients, both of which had a prevalence of 27.93%. after that, pathologic q wave and lbbb were the most common with 18.44% and 17.88%, respectively (14). in the study by maurits van bree et al. in 2010 in netherlands, the most common ecg changes among patients with brain stroke were qtc prolongation (36%), morphologic changes in st-t (23%), sinus bradycardia (16%), and inverted t wave (16%) and, respectively (15). in a study by marini et al. in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. asadi et al. 4 2005 in italy, which evaluated af and outcome of stroke, af was observed in the beginning and during the acute phase in 24.6% of the patients with stroke (13), which is close to the rate of af prevalence observed among the stroke patients in the present study. marini et al. in 2005 stated that the probability of 30-day and 1-year mortality in patients with stroke correlated with changes in ecg and age (13). increase in mortality in older ages can be evaluated from different perspectives. first, older patients have less recovery power compared to younger patients and on the other hand, patients with older ages are more exposed to risk factors of stroke such as hyperlipidemia, hypertension, atherosclerosis, and other cardiovascular diseases that overall lead to an increased mortality in older patients (16-19). in addition, the rate of mortality was significantly higher in patients with a history of cardiovascular diseases in the present study, which is in line with the findings of previous studies (19). mortality rate was 14.1% among patients with stroke with normal ecg, while in stroke patients with abnormal ecg the rate increased to 45.1%. the rate of mortality in patients with inverted t wave as the most common change in ecg among patients was 59.3%. in the present study, the highest rate of mortality in stroke patients who had changes in ecg, belonged to those who had af with 73.8%. bozluolcay et al in 2003 in turkey reported the rate of mortality in stroke patients with abnormal ecg to be 38.9% versus 15.2% in those who had a normal ecg (20). in the study by marini et al. it was expressed that among patients with stroke, 32.5% of those who had af died within 30 days and 49.5% died within a year; meanwhile, mortality rate for patients without af was 16.2% and 27.1% during 30 days and 1 year, respectively (13), which is very different from the findings of the present study. the disagreement might be due to the differences in the studied populations and sampling methods of the studies. in the study by koochaki et al. in 2012, it was shown that ecg abnormalities are common in patients with acute ischemic stroke and cardiac evaluations should have predictive value (14). in the present study, after performing regression test, it was revealed that ecg changes in patients with stroke increase the odds of mortality about 4 times. additionally, in a study by goldstein it was reported that changes in ecg elevate the probability of mortality to 4.82 times (21), which is similar to the finding of the present study. from the results of the present study and previous ones, it can be concluded that ecg changes, especially st segment changes, inverted t wave, and af, are very common in patients with ischemic stroke and are associated with increased mortality in these patients along with factors such as age and presence of cardiac diseases. of course for generalizing the results of this study, there is still need for more accurate studies by eliminating the limitations of the present and previous studies. 5. limitation in the present study, some of the potential factors affecting the outcome of patients with ischemic stroke, such as the size of the ischemic region, were not evaluated; it is suggested to assess imaging findings as one of the probable variables affecting outcome. in addition, in the present study, the time interval between manifestation of symptoms and presenting to the emergency department and undergoing electrocardiography has not been reported. however, it seems that this matter could affects development of complications such as increase in intracranial pressure and thus, the probability of developing the abnormal ecg findings caused by it. another very important limitation is that it is not known whether observed changes in ecg are new or old. for a more accurate study, only patients that have evidence of a normal ecg before the stroke should be included in the study. however, despite all of these limitations, the findings of the study can present a relatively accurate estimation of the current status for planning future studies. 6. conclusion based on the findings of the present study, it seems that along with age and history of cardiac diseases, changes in ecg can be considered as an independent factor predicting 1-year mortality of the patients with ischemic stroke. occurrence of ecg changes following stroke, increases the odds of 1-year mortality about 4 times. 7. appendix 7.1. acknowledgements all the staff members of poursina hospital, rasht, iran, are thanked for their cooperation throughout the study period. 7.2. author contribution all authors passed the criteria of authorship based on the recommendations of international committee of medical journal editors. authors’ orcids payman asadi: 0000-0002-3625-4163 seyyed mahdi zia ziabari: 0000-0002-0329-8653 7.3. funding/support no financial support has been received for carrying out this project. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e27 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. feigin vl. stroke in developing countries: can the epidemic be stopped and outcomes improved? the lancet neurology. 2007;6(2):94-7. 2. strong k, mathers c, bonita r. preventing stroke: saving lives around the world. the lancet neurology. 2007;6(2):182-7. 3. thom t, haase n, rosamond w, howard vj, rumsfeld j, manolio t, et al. heart disease and stroke statistics– 2006 update: a report from the american heart association statistics committee and stroke statistics subcommittee. circulation. 2006;113(6):e85. 4. shahpouri mm, mousavi s, khorvash f, mousavi sm, hoseini t. anticoagulant therapy for ischemic stroke: a review of literature. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2012;17(4):396-401. 5. weimar c, ziegler a, konig ir, diener h-c. predicting functional outcome and survival after acute ischemic stroke. journal of neurology. 2002;249(7):888-95. 6. agarwal sk, soliman ez. ecg abnormalities and stroke incidence. expert review of cardiovascular therapy. 2013;11(7):853-61. 7. togha m, sharifpour a, ashraf h, moghadam m, sahraian ma. electrocardiographic abnormalities in acute cerebrovascular events in patients with/without cardiovascular disease. annals of indian academy of neurology. 2013;16(1):66-71. 8. popescu d, cristina l, mergeani a, bajenaru oa, antochi fa. lead electrocardiogram changes after supratentorial intracerebral hemorrhage. maedica. 2012;7(4):290-4. 9. khechinashvili g, asplund k. electrocardiographic changes in patients with acute stroke: a systematic review. cerebrovascular diseases. 2002;14(2):67-76. 10. laowattana s, zeger s, lima j, goodman s, wittstein i, oppenheimer s. left insular stroke is associated with adverse cardiac outcome. neurology. 2006;66(4):477-83. 11. christensen h, boysen g, christensen a, johannesen h. insular lesions, ecg abnormalities, and outcome in acute stroke. journal of neurology, neurosurgery & psychiatry. 2005;76(2):269-71. 12. christensen h, christensen af, boysen g. abnormalities on ecg and telemetry predict stroke outcome at 3 months. journal of the neurological sciences. 2005;234(1):99-103. 13. marini c, de santis f, sacco s, russo t, olivieri l, totaro r, et al. contribution of atrial fibrillation to incidence and outcome of ischemic stroke results from a population-based study. stroke. 2005;36(6):1115-9. 14. ebrahim k, mohamadali a, majid m, javad a. electrocardiograph changes in acute ischemic cerebral stroke. journal of applied research in clinical and experimental therapeutics. 2012;12(1):53. 15. van bree md, roos yb, van der bilt ia, wilde aa, sprengers me, de gans k, et al. prevalence and characterization of ecg abnormalities after intracerebral hemorrhage. neurocritical care. 2010;12(1):50-5. 16. joffres m, falaschetti e, gillespie c, robitaille c, loustalot f, poulter n, et al. hypertension prevalence, awareness, treatment and control in national surveys from england, the usa and canada, and correlation with stroke and ischaemic heart disease mortality: a crosssectional study. bmj open. 2013;3(8):e003423. 17. rutten-jacobs lc, arntz rm, maaijwee na, schoonderwaldt hc, dorresteijn ld, van dijk ej, et al. long-term mortality after stroke among adults aged 18 to 50 years. jama. 2013;309(11):1136-44. 18. schmidt m, jacobsen jb, johnsen sp, botker he, sorensen ht. eighteen-year trends in stroke mortality and the prognostic influence of comorbidity. neurology. 2014;82(4):340-50. 19. go as, mozaffarian d, roger vl, benjamin ej, berry jd, blaha mj, et al. aha statistical update. circulation. 2013;127:e62-e245. 20. bozluolcay m, ince b, celik y, harmanci h, ilerigelen b, pelin z. electrocardiographic findings and prognosis in ischemic stroke. neurology india. 2003;51(4):500. 21. goldstein ds. the electrocardiogram in stroke: relationship to pathophysiological type and comparison with prior tracings. stroke. 1979;10(3):253-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2(3): 106 106 editorial peritoneal dialysis as an alternative choice for renal replacement therapy in emergency department iraj najafi* shafa capd research center, dialysis and transplant patients association (datpa), tehran, iran *corresponding author: iraj najafi; department of internal medicine, dr. shariati hospital, tehran university of medical sciences, north kargar avenue, tehran 14114 iran. tel/fax: +98 21 22721155; email: najafi63800@yahoo.com ncreasing the prevalence of renal failure cases needing renal replacement therapy (rrt) among refereeing to the emergency department highlights the preparation requirement for services giving to these patients. the limited number of hemodialysis machines, inaccessibility of dialysis machines in all hospitals, large number of patients, and shortage of expert personnel in this field are some of current problems of health centers to present services for these patients. since hemodialysis units are usually reserved for patients with chronic renal failure as overnight and weekly base, this problem would be exacerbate when the subjects need emergent dialysis. on the other hand, in acute critical patients who have hemodynamic instability or heart failure, hemodialysis is not tolerable then not treatment of choice. therefore, peritoneal dialysis can be considered as an alternative choice for emergent dialysis cases. the peritoneal dialysis method is one of the effective treatment strategies for dialyzed patients without need of expensive machines and equipment. this method has been tested on human since 1923, in which blood purification is performed through peritoneal membrane. in some countries more than 90% of patients are dialyzed through this way (1, 2). peritoneal dialysis is also expanding in iran and based on the policy of ministry of health at least 15% of dialyzed patients are to be dialyzed using this method in the country. for the first time, peritoneal dialysis has been performed in imam reza hospital, mashhad, iran, in 1993 and then after in two peritoneal dialysis center of tehran (3). today pd has been accepted as an efficient and reliable alternative way for rrt in acute as well as chronic renal failure. although there are several successful reports applying the peritoneal dialysis even in hyperkalemia, acidosis, uremic syndrome, and etc. (4-8), it has less been considered as a current alternative therapy for emergent dialysis cases. of course using this method is not limited only to the renal failure and can be used to remove dialyzable toxins such as barbiturates and ethylene glycol as well as treatment of severe electrolyte disturbance and peritonitis (1, 2). to reach this goal, bedside embedding peritoneal dialysis catheter is a critical and non-negligible point on management of the patients due to the dangerous situation of transporting these patients to operating room. we used to put a semi rigid temporary polyethylene catheter (trocath) with guidance of stylet introducer which no have been replaced by the flexible silicone rubber catheter introduced by tenckhoff. it has many advantages in comparison with the trocath catheters. its softness allows it to be tunneled subcutaneously in the anterior abdominal wall and its dacron single cuff reduced the incidence of complications such as, leakage, accidental dislodgement and infection. these catheters can be inserted as a bedside percutaneous procedure with local anesthesia as well as laparascopic and surgical methods. based on the above mentioned data, it seems that training of surgeons, internists, and emergency physicians regarding inserting percutaneously a pd catheter, and management of probable complications can be considered as essential steps toward a better handling of such an almost large group of patients in emergency wards. references: 1. avendano mbi, solorzano gy, valenzuela jr, et al. automated peritoneal dialysis as a lifesaving therapy in an emergency room: report of four cases. kidney int. 2008;73(s108):s173-s6. 2. labato ma. peritoneal dialysis in emergency and critical care medicine. clin tech small anim pract. 2000;15(3):12635. 3. mahdavi r, naghib m. kidney transplantation in children: results of ten years experience in imam reza hospital. med j islamic repub iran. 2002;16(3):145-9. 4. kilonzo kg, ghosh s, temu sa, et al. outcome of acute peritoneal dialysis in northern tanzania. perit dial int. 2012;32(3):261-6. 5. ajaz sm, pathan ms, badaam km. clinical profile, etiological factors and outcome of acute renal failure in children: a clinical study. hypertension. 2012;26:46.2. 6. najafi i, hakemi m, safari s, et al. the story of continuous ambulatory peritoneal dialysis in iran. perit dial int. 2010;30(4):430-3. 7. little d, custer md. peritoneal dialysis. fundamentals of pediatric surgery: springer; 2011. p. 553-7. 8. akhlaghi aa, najafi i, mahmoodi m, shojaee a, yousefifard m, hosseini m. survival analysis of iranian patients undergoing continuous ambulatory peritoneal dialysis using cure model. j res health sci. 2013;13(1):32-6. i emergency. 2018; 6 (1): e62 rev i ew art i c l e ubiquitin c-terminal hydrolase-l1 (uch-l1) in prediction of computed tomography findings in traumatic brain injury; a meta-analysis fatemeh ramezani1, amir bahrami-amiri2, asrin babahajian3 3, kavous shahsavari nia4, mahmoud yousefifard1∗ 1. physiology research center, faculty of medicine, iran university of medical sciences, tehran, iran. 2. occupational medicine research center, iran university of medical sciences, tehran, iran. 3. liver and digestive research center, kurdistan university of medical sciences, sanandaj, iran. 4. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. received: october 2018; accepted: october 2018; published online: 15 december 2018 abstract: introduction: ubiquitin c-terminal hydrolase-l1 (uch-l1) is one of the promising candidates, with an acceptable diagnostic value for predicting head computed tomography (ct) scan findings. however, there has been a controversy between studies and still, there is no general overview on this. therefore, the current systematic review and meta-analysis attempted to estimate the value of uch-l1 in predicting intracranial lesions in traumatic brain injury (tbi). methods: two independent reviewers screened records from the search of four databases medline, embase, scopus and web of science. the data were analyzed in the stata 14.0 statistical program and the findings were reported as a standardized mean difference (smd), summary receiver performance characteristics curve (sroc), sensitivity, specificity, and diagnostic odds ratio with 95% confidence interval (95% ci). results: finally, the data of 13 articles were entered into the meta-analysis. the mean serum level of uch-l1 was significantly higher in patients with ct-positive than in tbi patients with ct negative (smd = 1.67, 95% ci: 1.12 to 2.23, i2 = 98.1%; p <0.0001). the area under the sroc curve for uch-l1 in the prediction of intracranial lesions after mild tbi was 0.83 (95% ci: 0.80 to 0.86). sensitivity, specificity and diagnostic odds ratio of serum uch-l1 was 0.97 (95% ci: 0.92 to 0.99), 0.40 (95% ci: 0.30 to 0.51) and 19.37 (95% ci: 7.25 to 51.75), respectively. when the analysis was limited to assessing the serum level of uch-l1 within the first 6 hours after mild tbi, its sensitivity and specificity increased to 0.99 (95% ci: 0.94 to 1.0) and 0.44 (95% ci: 0.38 to 0.052), respectively. in addition, the diagnostic odds ratio of 6-hour serum level of uch-l1 in the prediction of intracranial lesions was 680.87 (95% ci: 50.50 to 9197.97). conclusion: moderate level of evidence suggests that serum/plasma levels of uch-l1 have good value in prediction of head ct findings. it was also found that evaluation of serum/plasma level of uch-l1 within the first 6 hours following tbi would increase its predictive value. however, there is a controversy about the best cutoffs of the uch-l1. keywords: ubiquitin c-terminal hydrolase-l1; traumatic brain injuries; diagnosis; brain computed tomography © copyright (2018) shahid beheshti university of medical sciences cite this article as: ramezani f, bahrami-amiri a, babahajian a, shahsavari nia k, yousefifard m. ubiquitin c-terminal hydrolase-l1 (uchl1) in prediction of computed tomography findings in traumatic brain injury; a meta-analysis. emergency. 2018; 6(1): e62. ∗corresponding author: mahmoud yousefifard; assistant professor of physiology, physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354; tel: +982186704771 fax: +982186704771, e-mail: yousefifard.m@iums.ac.ir 1. introduction t raumatic brain injury (tbi) is one of the most common causes of death and disability with a global prevalence of 8.4%. incidence, prevalence, and years of life lost due to tbi increased significantly from 1990 to 2016 (1). this increasing burden has led to a substantial increase in the tbi-related emergency visits. intracranial this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. ramezani et al. 2 lesions caused by tbi are diagnosed mainly with imaging assessments such as computed tomography (ct) scan and magnetic resonance imaging (mri). however, for two reasons, the use of imaging techniques in emergency departments is not feasible. first, there is no access to ct scan and mri in all emergency departments, and secondly, imaging is not possible for all trauma patients. in addition, exposure to ionizing radiation as a result of ct scan should not ignore (2, 3). therefore, researchers are looking for other diagnostic or screening modalities that can be used to detect the intracranial lesion. patients with tbi are divided into three categories of mild, moderate and severe, based on clinical evaluations, in particular, glasgow coma scale (gcs). mild tbi is the most prevalent and physicians are always in trouble when patients need to go for radiography for further evaluation. estimates have shown that about 16% of mild tbi patients have intracranial lesions (4). this means that if all mild tbi patients undergo ct scan or mri, 84% of these imaging is unnecessary. to reduce this excessive imaging, screening tests such as serum biomarkers can be effective. several biomarkers such as s100-b and neuron-specific enolase have been proposed to predict central nervous system injuries (5-7), but there is still a controversy between literature, and researchers are still looking for other biomarkers. of these, ubiquitin c-terminal hydrolase-l1 (uch-l1) is one of the promising candidates with an acceptable value in the prediction of intracranial lesions (8). however, there has been a contention between studies and there is still no general overview of this area. therefore, the present systematic review and meta-analysis attempted to evaluate the value of uch-l1 in the prediction of intracranial lesions in tbi patients. 2. methods: 2.1. search strategy the present meta-analysis was designed to determine the value of uch-l1 in predicting of head ct findings. for this purpose, an extensive search was performed in medline (via pubmed), embase, scopus, and web of science. the search terms were related to tbi in combination with the uch-l1. the medline search query is provided below. in addition, the search was done manually in the bibliography of relevant studies and review articles. google’s search engine was also searched for gray literature. 2.2. pubmed search query: 1"ubiquitin thiolesterase"[mh] or "thiolesterase, ubiquitin"[tiab] or "ubiquitin c-terminal hydrolase"[tiab] or "c-terminal hydrolase, ubiquitin"[tiab] or "hydrolase, ubiquitin c-terminal"[tiab] or "ubiquitin c terminal hydrolase"[tiab] or "ubiquitin carboxy-terminal hydrolase"[tiab] or "carboxy-terminal hydrolase, ubiquitin"[tiab] or "hydrolase, ubiquitin carboxy-terminal"[tiab] or "ubiquitin carboxy terminal hydrolase"[tiab] or "ubiquitin c-terminal esterase"[tiab] or "c-terminal esterase, ubiquitin"[tiab] or "esterase, ubiquitin cterminal"[tiab] or "ubiquitin c terminal esterase"[tiab] or "ubiquitin carboxy-terminal esterase"[tiab] or "carboxyterminal esterase, ubiquitin"[tiab] or "esterase, ubiquitin carboxy-terminal"[tiab] or "ubiquitin carboxy terminal esterase"[tiab] or "ubiquitin carboxyl-terminal hydrolase isozyme l1"[tiab] or "ubiquitin carboxyl terminal hydrolase isozyme l1"[tiab] or "parkinson disease 5 protein"[tiab] or "park5 protein"[tiab] or "neuron cytoplasmic protein 9.5"[tiab] or "uchl1 protein"[tiab] or "uch-l1 protein"[tiab] or "uch l1 protein"[tiab] or "uchl1"[tiab] 2"brain concussion"[mh] or "brain injuries"[mh] or "brain injuries, traumatic"[mh] or "brain concussion"[tiab] or "brain injuries"[tiab] or "brain injuries, traumatic"[tiab] or "brain concussions"[tiab] or "concussion, brain"[tiab] or "commotio cerebri"[tiab] or "cerebral concussion"[tiab] or "cerebral concussions"[tiab] or "concussion, cerebral"[tiab] or "concussion, intermediate"[tiab] or "intermediate concussion"[tiab] or "intermediate concussions"[tiab] or "concussion, severe"[tiab] or "severe concussion"[tiab] or "severe concussions"[tiab] or "concussion, mild"[tiab] or "mild concussion"[tiab] or "mild concussions"[tiab] or "mild traumatic brain injury"[tiab] or "injuries, brain"[tiab] or "brain injury"[tiab] or "injury, brain"[tiab] or "injuries, acute brain"[tiab] or "acute brain injuries"[tiab] or "acute brain injury"[tiab] or "brain injury, acute"[tiab] or "injury, acute brain"[tiab] or "brain injuries, acute"[tiab] or "brain lacerations"[tiab] or "brain laceration"[tiab] or "laceration, brain"[tiab] or "lacerations, brain"[tiab] or "brain injuries, focal"[tiab] or "brain injury, focal"[tiab] or "focal brain injury"[tiab] or "injuries, focal brain"[tiab] or "injury, focal brain"[tiab] or "focal brain injuries"[tiab] or "brain injury, traumatic"[tiab] or "traumatic brain injuries"[tiab] or "trauma, brain"[tiab] or "brain trauma"[tiab] or "brain traumas"[tiab] or "traumas, brain"[tiab] or "tbi (traumatic brain injury)"[tiab] or "encephalopathy, traumatic"[tiab] or "encephalopathies, traumatic"[tiab] or "traumatic encephalopathies"[tiab] or "injury, brain, traumatic"[tiab] or "traumatic encephalopathy"[tiab] or "tbis (traumatic brain injuries)"[tiab] or "tbi (traumatic brain injuries)"[tiab] or "traumatic brain injury"[tiab] or "tbi"[tiab] 3#1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e62 figure 1: prisma flow diagram of present meta-analysis. figure 2: assessment of risk of bias, applicability (a) and publication bias (b) among eligible studies. no publication bias was observed (p=0.362). 2.3. selection criteria all of the observational studies on the predictive value of uch-l1 in the prediction of head ct findings were included. exclusion criteria were chronic exposure to head trauma, penetrating tbi, non-traumatic injury, lack of data, and reviews. 2.4. data extraction and quality assessment the method of summarizing data has been reported in our previous meta-analyses study (9-23). two independent reviewers screened records from the database. the potentially relevant studies were assessed in detail and finally, based on the selection criteria eligible studies were identified. the reviewers recorded the type of study (cohort, case-control, cross-sectional, etc.), the age range of patients, sample size this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. ramezani et al. 4 table 1: summary characteristics of studies author; year; country type of study age* ct/ ct+ male gender sampling methods time to sample# method assay gcs bazarian; 2018; usa cohort 18-98 1793/122 1107 convenience 0 to 12 elisa 9-15 diaz-arrastia; 2014; usa cohort 37±14 40 / 31 150 nr 0 to 24 elisa 14-15 dickens; 2018; finland and uk cohort 18-91 95 / 114 152 nr 0 to 12 elisa 13-15 korley; 2016; usa cohort 26-56 84 / 75 215 convenience 0 to 24 elisa 3-15 korley; 2018; usa cohort 24-61 63 / 44 78 convenience 0 to 24 elisa 3-15 lewis; 2017; usa trial 18-80 154 / 34 116 nr 0 to 24 elisa 13-15 mondello; 2016; usa cohort 3.8±3.7 10 / 29 28 nr 0 to 24 elisa 3-15 papa; 2012; usa cohort 18-89 77 / 28 64 convenience 0 to 4 elisa 9-15 papa; 2016; usa cohort 18-83 290 / 35 212 convenience 0 to 24 elisa 9-15 papa; 2017; usa cohort 0-21 134 / 17 100 convenience 0 to 6 elisa 9-15 posti; 2016; finland and uk cohort 45.3±19.2 90 / 200 239 consecutive 0 elisa 3-15 welch; 2016; usa cohort 18-80 215 / 36 151 nr 0 to 6 elisa 13-15 welch; 2017; usa cohort 18-80 134 / 33 102 nr 0 elisa 9-15 *, data are presented as mean ± standard deviation or age range. #, hours from traumatic brain injury (tbi). ct: computed tomography; gcs: glasgow coma scale of patients at admission; elisa: enzyme-linked immunosorbent assay; nr: not reported. table 2: quality assessment of included articles based on quadas-2 guideline author; year risk of bias applicability patient selection index test reference standard flow and timing patient selection index test reference standard bazarian; 2018 § © © © © © © diaz-arrastia; 2014 ? © © © © © © dickens; 2018 ? © © © © © © korley; 2016 § © © © © © © korley; 2018 § © © © © © © lewis; 2017 ? © © © © © © mondello; 2016 ? © © © © © © papa; 2012 § © © © © © © papa; 2016 § © © © © © © papa; 2017 § © © © © © © posti; 2016 © © © © © © © welch; 2016 ? © © © © © © welch; 2017 ? © © © © © © ©: low risk; §: high risk; ?: unclear risk (number of ct positive and ct negative tbi patients), male gender frequency, sampling method (random, consecutive, convenience), the method of uch-l1 assay, tbi severity and outcomes. the severity of tbi was divided into three groups, mild (gcs: 13 to 15), moderate (gcs: 9 to 12) and severe (gcs: 3 to 8). the evaluated outcomes included the mean serum level of uch-l1 in both ct positive and ct negative groups and the number of true positive (tb), true negative (tn), false positive (fp) and false negative (fn). in some articles, the mean serum level of uch-l1 was reported in the graphs. in these cases, using the plot digitizer software (available at http://plotdigitizer.sourceforge.net/), the mean and standard deviation of the serum level of this biomarker were extracted. in addition, many articles were not reported tp, tn, fp, and fn cases. therefore, tp, tn, fp, and fn were estimated using the reported sensitivity and specificity. quality control of the eligible studies was evaluated using the proposed method of quality assessment of diagnostic accuracy studies 2 (quadas-2) guideline (24). 2.5. statistical methods data were analyzed in the stata 14.2 program. metaanalysis was performed in two sections. in the first part, the mean serum level of uch-l1 was compared in ct positive and ct negative groups. in this section, the standardized mean difference (smd) was calculated and finally, an overall smd with a 95% confidence interval (95% ci) was reported. in the second section, using the tp, tn, fp, and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e62 table 3: sensitivity analysis for performance of serum level of ubiquitin c-terminal hydrolase l1 in detection of intracranial lesion (based on computed tomography findings) in mild traumatic brain injuries variable sensitivity specificity diagnostic score diagnostic odds ratio age group children na na na na adult 0.96 (0.92 to 0.98) 0.39 (0.29 to 0.51) 2.82 (1.86 to 3.77) 16.72 (6.44 to 43.39) timing (hours after tbi) 0 to 6 0.99 (0.94 to 1.0) 0.44 (0.38 to 0.52) 6.52 (3.92 to 9.12) 680.87 (50.50 to 9197.97) >6 na na na na overall 0.97 (0.92 to 0.99) 0.40 (0.30 to 0.51) 2.96 (1.98 to 3.95) 19.37 (7.25 to 51.75) all data are presented with 95% confidence interval. figure 3: forest plot for serum level of ubiquitin c-terminal hydrolase l1 in traumatic brain injury (tbi) subjects with positive computed tomography (ct) findings compared to negative ct findings. ci: confidence interval; smd: standardized mean difference. fn data, the summary receiver operating characteristic curve (sroc), sensitivity, specificity, diagnostic score, and diagnostic odds ratio of uch-l1 in the prediction of ct findings were reported. i2 test was used to assess heterogeneity and eager’s test was used to evaluate the publication bias. in all analyzes p <0.05 was defined as significant level. 3. results: 3.1. study characteristics finally, 13 articles provided data suitable for meta-analysis (figure 1) (8, 25-36). they were 12 cohort studies and 1 observational trial. these studies included 3977 patients with tbi. ct scan findings in 3179 (79.93%) patients were negative and in 798 (20.07%) were positive. the serum sample was obtained in five studies during the first 6 hours after the onset of tbi. in two studies, it was assessed within 12 hours and in six studies over the first 24 hours after tbi. four studies were conducted on mild tbi, five with mild to moderate tbi and four with mild to severe tbi patients. table 1 shows a summary of the eligible studies. 3.2. quality control and risk of bias quality assessment of the relevant studies according to the quadas-2 guidelines showed that the risk of bias in patient selection was high or unclear in 12 studies. other items in all studies were rated as the low risk of bias (figure 2a and table 2). there was no publication bias in the present study (p = 0.362) (figure 2b). 3.3. meta-analysis comparison of mean serum/plasma uch-l1 in ct positive and ct negative patients the mean value of serum/plasma levels of uch-l1 reported in each of the 13 papers were investigated (8, 25-36). the analyzes showed that the mean serum/plasma level of uch-l1 was significantly higher in ct-positive tbi than in ct negative tbi patients (smd = 1.67, 95% ci: 1.12 to 2.23, p <0.0001; i2 = 98.1%, p < 0.0001) (figure 3). the mean serum/plasma level of uch-l1 within 6 hours after tbi (smd = 1.72, 95% ci: 0.98 to 2.47, p <0.0001), during the first 12 hours after injury (smd = 1.74, 95% ci: 0.42 to 3.07, p = 0.01) and 24 hours later (smd = 1.55, 95% ci: 0.88 to 2.21, p <0.0001) in ct positive tbi patients were always higher than ct negative patients. screening performance characteristics in the detection of an intracranial lesion in mild tbi six studies, including 15 separate experiments evaluated the performance of uch-l1 in the prediction of intracranial lesions (8, 25, 26, 29, 30, 33). the cut off used in the studies varied between 41 pg/ml and 327 pg/ml. 11 experiments were performed on mild tbi, three experiments on mild to moderthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. ramezani et al. 6 figure 4: summary of receiver operating curve (sroc) of serum level of ubiquitin c-terminal hydrolase l1 in detection of intracranial lesion (based on computed tomography findings) in mild and mild to severe traumatic brain injuries (tbi). auc: area under the curve; sens: sensitivity; spec: specificity. ate tbi and one experiment on mild to severe tbi. therefore, the analyzes of this section focused on mild tbi. the area under the sroc curve for serum/plasma uch-l1 in the prediction of intracranial lesions after mild tbi was 0.83 (95% ci: 0.80 to 0.86) (figure 4). the sensitivity and specificity of this serum biomarker were 0.97 (95% ci: 0.92 to 0.99) and 0.40 (95% ci: 0.30 to 0.51), respectively. the diagnostic odds ratio of uch-l1 in the prediction of intracranial lesions after mild tbi was 19.37 (95% ci: 7.25 to 51.75) (figure 5). when the analysis was limited to assessing the serum/plasma uch-l1 level within the first 6 hours after mild tbi, its sensitivity and specificity increased to 0.99 (95% ci: 0.94 to 1.0) and 0.44 (95% ci: 0.38 to 0.052), respectively. the diagnostic odds ratio of 6-hour uch-l1 in the prediction of intracranial lesions was 680.87 (95% ci: 50.50 to 9197.97) (table 3). 4. discussion: the present meta-analysis showed that after tbi, the serum/plasma uch-l1 level increased significantly. therefore, it could be used as a biomarker to detect intracranial lesions. the area under the sroc of uch-l1 in prediction of head ct scan findings was 0.83. serum/plasma uch-l1 has a high sensitivity (0.97) to predict intracranial lesions but its specificity (0.40) is low. since the role of using biomarkers in the clinic is more focused on its screening value, the high sensitivity of uch-l1 in predicting intracranial lesions is an advantage, while its low specificity is not a major weakness in the use of uch-l1 in the management of tbi. however, it is necessary to introduce an optimum cut off for the serum/plasma level of uch-l1. the cut offs used in the studies were between 41 pg / ml and 327 pg / ml. therefore, in the current meta-analysis, the assessment of the best cut offs for the uch-l1 was not possible. therefore, further studies are recommended. the diagnostic/predictive value of biomarkers varies with time (37, 38). since, decision making in tbi patients is performed during the first 24 hours of injury, the 24-hour serum/plasma uch-l1 level was analyzed in the current meta-analysis. the findings indicate that the performance of uch-l1 is higher in the first 6 hours of tbi than in the next few hours. therefore, it seems that evaluating this biomarker as soon as possible can provide valuable information about the severity of tbi. in a similar meta-analysis study, shahjouei et al. showed that the serum/plasma level of uch-l1 has a moderate value in the prediction of intracranial lesions (39). this report was different from the findings of the present study. shahjouei et al., included data from four studies, while in the present study, data from six studies containing 15 separate experiments were entered. on the other hand, the conclusion presented by shahjouei et al is based on the area under the curve of uch-l1, while our findings were presented based on tp, tn. fp, and fn. in addition, the area under the curve simultaneously represents sensitivity and specificity. in the present study, the uch-l1 has a high sensitivity that is very suitable this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e62 figure 5: performance of serum level of ubiquitin c-terminal hydrolase l1 in detection of intracranial lesion (based on computed tomography findings) in mild traumatic brain injuries. a) sensitivity and specificity; b) diagnostic score and diagnostic odds ratio. for a screening test, but has a low specificity that does not play a critical role in screening of patients. therefore, it is not possible to accurately discuss about the value of a screening biomarker just by reporting the auc. many articles do not report tp, tn, fp, and fn and instead provide sensitivity and specificity. to overcome this problem, using standard methods and web-based applications, tp, tn, fp, and fn were obtained from sensitivity and specificity. this was one of the strengths of the present study. however, in the present study due to the high diversity among eligible studies, it was not possible to report the best cut off for serum/plasma level of uch-l1. there was also a significant heterogeneity between studies. unfortunately, we did not find the source of heterogeneity. therefore, for these reasons, the evidence presented in this study was reduced to a moderate level. 5. conclusion a moderate level of evidence suggests that the serum/plasma level of uch-l1 had good value in prediction of head ct findings. it was also found that evaluation of serum/plasma level of uch-l1 within the first 6 hours after tbi would increase its predictive value. however, there is a controversy about the best cut offs of the uch-l1 and further studies are needed. 6. appendix 6.1. acknowledgements none. 6.2. authors’ contributions my and fr designed the study. my, ab, aba collected the data. my and ks analyzed the data and interpreted the results. my and fr wrote the manuscript. all authors critically revised the paper. authors’ orcids fatemeh ramezani: 0000-0001-7359-4880 amir bahrami-amiri: 000-0001-9472-4429 asrin babahajian: 0000-0003-0278-1560 kavous shahsavari nia: 0000-0002-4049-8531 mahmoud yousefifard: 0000-0001-5181-4985 6.3. funding support none. 6.4. conflict of interest there was no conflict of interest. references 1. badhiwala jh, wilson jr, fehlings mg (2018) global burden 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(2018) the diagnostic values of uch-l1 in traumatic brain injury: a metaanalysis. brain inj 32(1):1-17. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods: results: discussion: conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e60 br i e f re p o rt incidental findings of computed tomography angiography in patients suspected to pulmonary embolism; a brief report mustafa korkut1, cihan bedel1∗, kürsat erman2, serkan yüksel3 1. department of emergency medicine, health science university, antalya training and research hospital, antalya, turkey. 2. department of radiology, akdeniz university faculty of medicine, antalya, turkey. 3. department of radiology, health science university, antalya training and research hospital, antalya, turkey. received: august 2019; accepted: september 2019; published online: 22 october 2019 abstract: introduction: computed tomography pulmonary angiography (ctpa) scans are increasingly used in emergency department (ed). therefore, the observation of incidental findings (ifs) has also increased. this study aimed to evaluate the frequency of ifs in patients who underwent ctpa. methods: all consecutive patients that underwent ctpa scanning for pulmonary embolism (pe) rule out between january 2017 and june 2018 were analysed. incidental findings were divided into and reported in three categories: group 1 potentially life-threatening, group 2 required follow up, and group 3 with limited clinical significance. results: 151 cases with the mean age of 61.2 ± 17.6 years were studied (54.3% female). pe was documented in 77 cases (50.9%). 448 ifs were detected (3 ifs were found per patient). 60 (13.3%) ifs were classified as group 1, 180 (40.1%) as group 2, and 208 (46.6%) as group 3. cardiomegaly was the most frequent finding in group 1 (n=32), followed by aortic aneurysm (n=13). in group 2, pleural effusion (n=58) and pneumonia (n=36) were the most frequent incidental findings. lung structure changes (n=92) and thoracic bone related findings (n=43) were the most common ifs observed in group 3. conclusion: ifs were detected in the majority of patients that underwent ctpa. most of these findings do not require follow-up or treatment. however, more than 50% of cases may require further diagnostic evaluation (40.1%) or immediate treatment (13.3%). keywords: pulmonary embolism; tomography; incidental findings; emergencies cite this article as: korkut m, bedel c, erman k, yüksel s. incidental findings of computed tomography angiography in patients suspected to pulmonary embolism; a brief report. arch acad emerg med. 2019; 7(1): e60. 1. introduction pulmonary embolism (pe) is a challenging diagnosis in emergency department (ed) characterized by high morbidity and mortality (1). early diagnosis and treatment can reduce the mortality rate of this disease (2). the symptoms and clinical signs of pe are non-specific and many thoracic pathologies such as pneumonia and aortic dissection cause similar symptoms (3, 4). computed tomography pulmonary angiography (ctpa) scanning is increasingly used as a diagnostic technique in pe patients. the disadvantages of ctpa ∗corresponding author: cihan bedel; health science university, antalya training and research hospital, kazim karabekir street, muratpasa, antalya, turkey. postal zip code: 07100, tel: +905075641254, fax: +902422494487, email: cihanbedel@hotmail.com are radiation exposure, contrast induced nephropathy, and cost (5). the main advantage of this imaging concept is being quick and providing information on all thoracic structures including lung parenchyma (6). another point of interest is the observation of incidental findings (ifs) on pe scanning. these findings can be irrelevant to the clinical scenario and might necessitate further investigations and treatment (7). based on the above-mentioned points, the aim of this study was to evaluate the frequency of ifs in patients who underwent ctpa scanning for pe rule out. 2. methods 2.1. study design and setting this retrospective cross-sectional study was performed on patients who underwent ctpa in ed of health science university antalya training and research hospital, antalya, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. korkut et al. 2 turkey, between january 1, 2017 and june 30, 2018. the study protocol was approved by ethics committee of the hospital (ethics code: 2019-235). 2.2. participants the study population consisted of all patients for whom a ctpa was ordered in the ed evaluation. the ctpa images of the patients included in the study were interpreted by two radiologist. ctpas obtained in other hospitals, were not included if the images were not retrievable on the workstation to be submitted for interpretation. 2.3. data gathering the patients’ data were accessed via the automation system of the hospital and admission files. the ctpa was read as positive for pe if filling defects were noted in the pulmonary arterial tree. if the scan yielded a positive result for thrombosis, intravenous localization was also recorded. if there were any ifs, they were observed as well. a negative scan result was also registered. all patients were examined using eclos 16-section computed tomography scanner (hitachi medical systems, tokyo, japan) in the ed. the ctpa images were obtained from the picture archival computer system (pacs). ifs were classified into three categories (major, moderate, and minor) by lumbreras et al. depending on severity (8). as in literature, in our study ifs were classified into three groups, too. group 1 included major or potentially lifethreatening findings such as abdominal aortic aneurysm and a new-found malignancy. group 2 included moderate findings that could require diagnostic follow-up and group 3 included minor findings with limited clinical significance like anatomic variants. 2.4. statistical analysis descriptive statistical analysis of all variables was performed using spss 18.0. mean ± standard deviation for continuous variables and number (%) of non parametric data were calculated and reported. 3. results: 151 cases with the mean age of 61.2 ± 17.6 years were studied (54.3% female). pe was documented in 77 cases (50.9%). thrombus was detected in main pulmonary arteries in 27 (16.7%) patients, segmental arteries in 62 (38.5%), and subsegmental arteries in 72 (44.7%) cases. 448 ifs were detected (3 ifs were found per patient). 60 (13.3%) ifs were classified as group 1, 180 (40.1%) as group 2, and 208 (46.6%) as group 3 (table 1). cardiomegaly was the most frequent finding in group 1 (n=32), followed by aortic aneurysm (n=13) and malignancies such as adrenal tumor. in group 2, pleural effusion (n=58) and pneumonia (n=36) were the most frequent incitable 1: incidental findings in cases suspected to pulmonary embolism who underwent computed tomography angiogarpgy incidental findings number (%) group1 (n = 60) bronchial cancer 3 (5.0) aortic aneurysm 13 (21.7) liver metastasis 5 (8.3) adrenal tumour 1 (1.7) pulmonary mass 2 (3.3) mediastinal mass 4 (6.7) cardiomegaly 32 (53.3) group 2 (n = 180) pulmonary nodules 21 (11.7) pleural effusion 58 (32.2) cholecystolithiasis 4 (2.2) pneumonia 36 (20) thyroid nodule 13 (7.2) pancreatitis 1 (0.6) pericardial effusion 6 (3.3) significant atelectasis 17 (9.4) hiatal hernia 8 (4.4) ascites 2 (1.1) ileus 1 (0.6) pulmonary artery enlargement 10 (5.6) atrophic kidney 1 (0.6) bochdalek hernia 2 (1.1) group 3 (n = 208) renal cyst 23 (11.1) hepatic cyst 4 (1.9) lung structure changes 92 (44.2) splenomegaly 3 (1.4) adenopathy 10 (4.8) coronary artery calcification 31(14.9) bone finding 43 (20.7) hemangioma 1 (0.5) atrophic kidney 1 (0.5) data are presented as mean ± standard deviation or number (%). there is missing data in some variables. gcs: glasgow coma scale. dental findings. lung structure changes (n=92) and thoracic bone-related findings (n=43) were the most common ones observed in group 3. figure 1 shows examples of some detected ifs. 4. discussion the present study showed that ctpa detected ifs in the majority of patients. most of these findings do not require further evaluation or treatment. however, some may require follow-up and immediate treatment. in this study, 13.3% of detected ifs required emergent evaluation and 40.1% were in need for further diagnostic evaluation. ctpa has become the imaging test of choice in many institutions for diagnosis of pe because of high interobserver agreement, detection of other pathologies and cost-effectiveness this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e60 figure 1: examples of incidental finding among cases that underwent computed tomography angiography. (9). when we compare other imaging modalities, such as ventilation / perfusion scintigraphy, with ctpa, one of the most important advantages of ctpa is allowing us to perform pulmonary vascular examination as well as parenchymal, mediastinal, cardiac, pleural structures, thoracic wall, and upper abdominal organ evaluations (9, 10). another interesting point is the incidence of ifs in many patients, even though embolism is detected in approximately 1 in 5 with this imaging method. although most of these are benign, age-related changes, there may be findings that may require immediate treatment and follow-up. in this study, the prevalence of pe in ctpa was 51%. in previous studies this rate ranged from 19% to 79% (11). in this study, ifs were very common (about 3 findings for each patient). but more importantly, almost half of the patients had findings that required follow-up. approximately 13.3% of the studied cases had findings requiring immediate treatment; mostly pleural effusion (n=58). this frequency is consistent with a previous study on a similar population (12). frequency of patients with group 1 category ifs varied between 15% to 24% in previous studies (13, 14). hall et al. evaluated 589 patients and found a greater frequeny of ifs in need of emergent evaluation compared to our study. however, their high rate is due to inclusion of patients with major or potentially life-threatening findings and those with moderate findings that required diagnostic follow-up in the same category. the prevalence rate of pneumonia requiring follow-up has been reported to be 7.1% in ctpas in one study (14). in our case, the prevalence was (approximately 8%); however, it is significantly lower than that observed by hall et al. (13). the prevalence of lung nodules requiring follow-up was reported to be 25% in those undergoing ctpa (13). in our study, this prevalence was significantly lower. this can be partly due to the number of sections and image quality. since the number of ctpa slices in our study was low, incidental findings such as lung nodules could be expected to be less. we also observed a high rate of minor findings with no need for further examination. this trend was also observed in other studies examining the prevalence of incidental findings in ctpas (13, 15). turkvatan et al. reported a 56.2% incidence for clinically insignificant findings in 242 cohorts of patients screened with 16-line ct (16). however, perelas et al. reported 48.1% minor findings with no need for further examination, without classifing them by severity, in a cohort of 641 patients also scanned using a 16-slice ct (14). more importantly, relatively old studies reported innocent findings with diagnostic value for alternative diagnosis (9, 17). we believe that this ratio will increase with increase in image quality. it seems that, emergency physicians should be aware of these important ifs, and eds should also develop mechanisms to ensure appropriate follow-up for these patients. 5. limitation the study was conducted in a single center and in a retrospective manner and these results may not apply to different patient populations. lack of patient follow-up is one of our most important limitations. in some cases although the findings may appear to be characteristic tomography findings, the final histopathological diagnosis may be different. this may have caused overreporting of some findings, such as malignancy. 6. conclusion the present study showed that ctpa detected ifs in the majority of patients. most of these findings do not require follow-up or treatment. however, some may require followup and immediate treatment. in our study, 13.3% of ifs required emergent evaluation and 40.1% were in need for further evaluation according to their symptoms. 7. appendix 7.1. acknowledgements the author would like to thank md. asli bedel for helping in preparation of this paper. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. korkut et al. 4 7.2. author contribution all the authors have a substantial contribution in the study design, data interpretation and writing and reviewing the manuscript. authors orcids mustafa korkut: 0000-0003-1665-1601 cihan bedel: 0000-0002-3823-2929 7.3. funding no funding and support was received for this study. 7.4. ethical approval ethics committee approval was received for this study. 7.5. conflict of interest the author(s) declared that there is no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. references 1. jimenez d, martin-saborido c, muriel a, zamora j, morillo r, barrios d, et al. efficacy and safety outcomes of recanalisation procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis. thorax. 2018;73(5):464-71. 2. members atf, konstantinides sv, torbicki a, agnelli g, danchin n, fitzmaurice d, et al. 2014 esc guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (esc) endorsed by the european respiratory society (ers). european heart journal. 2014;35(43):3033-80. 3. dronkers c, huisman m, klok f. clinical presentation of acute pulmonary embolism. handbook of venous thromboembolism. 2017:21-6. 4. rosovsky r, zhao k, sista a, rivera-lebron b, kabrhel c. pulmonary embolism response teams: purpose, evidence for efficacy, and future research directions. research and practice in thrombosis and haemostasis. 2019;3(3):315-30. 5. aldridge es, rogers ir, mountain d, jones p. establishing an indicator rate for computed tomography pulmonary angiography positivity (yield) in emergency department pulmonary embolism investigation. emergency medicine australasia. 2018;30(1):134-5. 6. van der meer r, pattynama p. van strjen mj, van der berghuismans aa, hartmann ij, putter h, de roos, huisman mv. right ventricular dysfunction and pulmonary obstruction index at helical ct: prediction of clinical outcome during 3-month followup in patients with acute pulmonary embolism. radiology. 2005;235:798-803. 7. berlin l. the incidentaloma: a medicolegal dilemma. radiologic clinics. 2011;49(2):245-55. 8. lumbreras b, donat l, hernandez-aguado i. incidental findings in imaging diagnostic tests: a systematic review. the british journal of radiology. 2010;83(988):276-89. 9. van strijen m, bloem j, de monye w, kieft g, pattynama p, van den berg-huijsmans a, et al. helical computed tomography and alternative diagnosis in patients with excluded pulmonary embolism. journal of thrombosis and haemostasis. 2005;3(11):2449-56. 10. bernard bagattini s, bounameaux h, perneger t, perrier a. suspicion of pulmonary embolism in outpatients: nonspecific chest pain is the most frequent alternative diagnosis. journal of internal medicine. 2004;256(2):15360. 11. hogg k, brown g, dunning j, wright j, carley s, foex b, et al. diagnosis of pulmonary embolism with ct pulmonary angiography: a systematic review. emergency medicine journal. 2006;23(3):172-8. 12. battal b, karaman b, gumus s, akgun v, bozlar u, tasar m. the analysis of non-thromboembolic findings encountered in multidetector computed tomography pulmonary angiography studies in patients with suspected pulmonary embolism. turkish journal of emergency medicine. 2011;11(1):13-9. 13. hall wb, truitt sg, scheunemann lp, shah sa, rivera mp, parker la, et al. the prevalence of clinically relevant incidental findings on chest computed tomographic angiograms ordered to diagnose pulmonary embolism. archives of internal medicine. 2009;169(21):1961-5. 14. perelas a, dimou a, saenz a, rhee jh, teerapuncharoen k, rowden a, et al. incidental findings on computed tomography angiography in patients evaluated for pulmonary embolism. annals of the american thoracic society. 2015;12(5):689-95. 15. van es j, douma ra, schreuder sm, middeldorp s, kamphuisen pw, gerdes ve, et al. clinical impact of findings supporting an alternative diagnosis on ct pulmonary angiography in patients with suspected pulmonary embolism. chest. 2013;144(6):1893-9. 16. turkvatan a, akdur po, akgul a, olcer t, cumhur t, duru e. prevalence of incidental extracardiac findings on multidetector computed tomographic coronary angiography. turkiye klinikleri journal of medical sciences. 2009;29(1):169-75. 17. richman pb, courtney dm, friese j, matthews j, field a, petri r, et al. prevalence and significance of nonthromboembolic findings on chest computed tomography angiography performed to rule out pulmonary embolism: this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e60 a multicenter study of 1,025 emergency department patients. academic emergency medicine. 2004;11(6):642-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results: discussion limitation conclusion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2(2): 53 53 letter to editor the risk of venous thromboembolism associated with oral contraceptive; the search is still on ali abdalvand* department of family medicine, university of alberta, edmonton, canada cite this article as: abdalvand a. the risk of venous thromboembolism associated with oral contraceptive; the search is still on. emergency. 2014;2(2):53. dear editor: 1 few years after coming to the market, the first generation of oral contraceptive pills (ocps) were linked to significant risk of venous thromboembolism (vte). this increased risk was blamed on the presence of the estrogen-like compounds in these agents. therefore, the efforts were initiated to decrease the vte risk of ocps by lowering the delivered estrogen content by adding progestins such as levonorgestrel to these products, which led to production of the second generation of ocps. thereafter, the third generation of these agents with lower doses of progesterone-like compounds with contraceptive efficacy was released. they contain the new progestins such as drospirenone, norgestimate, desogestrel and gestodene (1-3). baratloo et al. review article (the risk of venous thromboembolism with different generation of oral contraceptives) is a good systematic review of the current evidence and concluded that taking second and third-generation ocps increases the risk of vte up to 3 and 4.3 fold, respectively (4). looking at the results of few other recent publications on the same subject reveals that risk of vte from oral contraceptives is more significantly associated with both estrogen dose and duration of use rather than progesterone type. the safest ocps in terms of vte are those containing levonorgestrel or norgestimate and the risk of vte associated with desogestrel, drospirenone or cyproterone acetate containing ocps is greater than that associated with ocps containing levonorgestrel. it is important to note the increase in vte due to third generation progestin pills was not associated with norgestimate but the increased risk was demonstrated with desogestrel and gestodene (5-8). the trend of this potentially lethal side effect of ocps needs to be viewed in the light of two facts: 1) nowadays, the use of ocps is not limited to contraception and we put patients on these medications for a plethora of *corresponding author: ali abdalvand; department of family medicine, university of alberta, edmonton, canada. phone/fax: +1(780)243-5596; email: abdalvand@yahoo.com received: 9 march 2014; accepted: 10 march 2014 medical condition. on top of that, global socioeconomical changes has increased the number of women who have access to ocps as well as the number of years these medications are taken continuously. 2) our advances in technology has given us the chance to be able to diagnose (and sometimes over diagnose!) some medical conditions such as vte. this would certainly affect the way we look at the medications and their side effects. nevertheless, ocps, as an integral part of the modern medicine and today’s lifestyle, are not completely safe and to make them a safer choice for patients, the search is still on. references: 1. rott h. thrombotic risks of oral contraceptives. curr opin obstet gynecol. 2012;24(4):235-40. 2. manzoli l, de vito c, marzuillo c, boccia a, villari p. oral contraceptives and venous thromboembolism. drug saf. 2012;35(3):191-205. 3. peck r, norris c. significant risks of oral contraceptives (ocps): why this drug class should not be included in a preventive care mandate. linacre q. 2012;79(1):41-56. 4. baratloo a, safari s, rouhipour a, et al. the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis. emergency. 2014;2(1):1-11. 5. martínez f, ramírez i, pérez-campos e, latorre k, lete i. venous and pulmonary thromboembolism and combined hormonal contraceptives. systematic review and meta-analysis. eur j contracept reprod health care. 2012;17(1):7-29. 6. gronich n, lavi i, rennert g. higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. can med assoc j. 2011;183(18):e1319-e25. 7. parkin l, sharples k, hernandez rk, jick ss. risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on uk general practice research database. bmj. 2011;342:d2139. 8. dinger j, assmann a, möhner s, do minh t. risk of venous thromboembolism and the use of dienogest-and drospirenone-containing oral contraceptives: results from a german case-control study. j fam plann reprod health care. 2010;36 (3):123-9. a archives of academic emergency medicine. 2020; 8(1): e29 rev i ew art i c l e potential treatments for covid-19; a narrative literature review ali rismanbaf1∗ 1. department of clinical pharmacy and pharmacy practice, school of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran. received: january 2020; accepted: february 2020; published online: 21 march 2020 abstract: sars-cov-2 is a newly emerging human infectious coronavirus that causes covid-19, which has been recognized as a pandemic by the world health organization (who) on march 11t h . there is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. therefore, in this article, new potential covid-19 therapies are briefly reviewed. keywords: coronavirus; drug therapy; clinical trial; case reports; review; covid-19 cite this article as: rismanbaf a. potential treatments for covid-19; a narrative literature review. arch acad emerg mede. 2020; 8(1): e29. 1. introduction sars-cov-2 (severe acute respiratory syndrome coronavirus 2) is a newly emerging human infectious coronavirus, originated in wuhan, china, and has been spreading rapidly in china and other countries since december 2019 (1). the world health organization (who) also declared a global emergency on january 31s t due to increasing concerns over its fast spread, and on march 11t h the disease was recognized as a pandemic. since the bases for pathogenesis of this virus and its proliferation is unclear, there is still no vaccine or definitive treatment against it. thus, medications used against sars-cov-2 are mainly based on their effectiveness on earlier strains of coronavirus, sars-cov and mers-cov. therefore, the immediate introduction of potential covid19 treatments can be essential and salvaging. in this article, new potential covid-19 therapies are briefly reviewed. 2. methodology articles were extracted, irrespective of time, using pubmed, embase, and google scholar search engines, searching terms "covid-19", "sars-cov-2", and "2019-ncov" in titles, abstracts and keywords. afterwards, clinical trials, clinical reports, case reports, and suggestions for potential medications against covid-19 were briefly reviewed. ∗corresponding author: ali rismanbaf; isfahan university of medical sciences, hezar jerib street, isfahan, iran. email: alirismanbaf74@gmail.com, tel: +989109747985 3. results 3.1. clinical reports clinical reports on covid-19 treatment mainly described empirical treatments and clinical experiences during its treatment. in 2020, gao et al. studied the effect of chloroquine and hydroxychloroquine in treatment of covid-19 in over 100 patients and 10 hospitals in wuhan, jingzhou, guangzhou, beijing, shanghai, chongqing, and ningbo. the results of this study showed that chloroquine phosphate is effective in preventing the exacerbations of pneumonia, decreasing lung involvements in imaging findings, promoting a virus-negative conversion and shortening the disease course. in addition, there were no serious adverse effects observed at therapeutic doses (2). also, according to jian-ya et al., treatment of 51 covid19 patients with traditional chinese medicine, interferon, lopinavir, ritonavir and short-term (3 to 5 days) corticosteroids was successful and resulted in recovery and discharge of 50 patients (3). qin et al. also reported that administration of moxifloxacin, lopinavir, and interferon to non-icu patients and the addition of methylprednisolone to the above treatment for icu patients resulted in 26 patients being discharged from intensive care unit (icu) and 16 patients being discharged from hospital (4). also, zhou et al. reported that short-term moderate-dose corticosteroid (160 mg/day) plus immunoglobulin (20 g/day) significantly reduced lung injury, normalized lymphocyte counts, body temperature, creactive protein levels, and oxygenation index in 10 covid19 patients (5). on the other hand, while studying 416 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rismanbaf 2 table 1: potential drugs for covid-19 study method medicine mechanism of action wang et al. (2020) (12) in vitro study chloroquine remdesivir reducing viral copy numbers in the cell supernatant and viral infection zhang et al. (2020) (13) in vitro study teicoplanin preventing the entrance of sarscov-2-spike-pseudoviruses into the cytoplasm xu et al. (2020) (14) virtual screening nelfinavir binding to sars-cov-2 mp r o liu et al. (2020) (15) virtual screening colistin valrubicin icatibant bepotastine epirubicin epoprostenol vapreotide aprepitant caspofungin perphenazine binding to sars-cov-2 mp r o shang et al. (2020) (16) virtual screening rupintrivir lopinavir remdesivir binding to sars-cov-2 mp r o jin et al. (2020) (17) virtual screening ebselen binding to sars-cov-2 mp r o sekhar et al. (2020) (18) virtual screening beclabuvir saquinavir binding to sars-cov-2 mp r o contini et al. (2020) (19) virtual screening (angiotensin ii human acetate) ghrp-2 indinavir cobicistat caspofungin acetate lopinavir atazanavir binding to sars-cov-2 mp r o : angiotensin ii human acetate, ghrp-2, indinavir, and cobicistat binding to sars-cov-2 3c-like proteinase (3clp r o ): angiotensin ii human acetate, ghrp-2, indinavir, caspofungin acetate, lopinavir, and atazanavir wang et al. (2020) (20) virtual screening carfilzomib eravacycline valrubicin lopinavir elbasvir streptomycin binding to sars-cov-2 protease wang et al. (2020) (21) virtual screening thymopentin carfilzomib saquinavir binding to sars-cov-2 3c-like proteinase (3clp r o ) chen et al. (2020) (22) virtual screening ledipasvir velpatasvir binding to sars-cov-2 3c-like proteinase (3clp r o ) beck et al. (2020) (23) molecule transformer-drug target interaction (mt-dti) atazanavir efavirenz ritonavir dolutegravir binding to sars-cov-2 3c-like proteinase (3clp r o ) elfiky et al. (2020) (24) virtual screening mycophenolic acid grazoprevir telaprevir boceprevir binding to sars-cov-2 papainlike protease (plp r o ) arya et al. (2020) (25) virtual screening formoterol chloroquine binding to sars-cov-2 papainlike protease (plp r o ) smith et al. (2020) (26) virtual screening eriodictyol isoniazid pyruvate nitrofurantoin cepharanthine ergoloid hypericin binding potency to viral s-protein at its host receptor region or to the s protein-human ace2 interface li et al. (2020) (27) connectivity map (cmap) ikarugamycin molsidomine effective on the genes coexpressed with ace2 richardson et al. (2020) (28) using benevolentai baricitinib binding to ap2-associated protein kinase 1 (aak1) nowak et al. (2020) (29) brief review lithium probably by reducing apoptosis and inhibition of glycogen synthase kinase 3 beta (gsk-3β) sun et al. (2020) (30) brief review angiotensin converting enzyme inhibitors and angiotensin1 receptor inhibitors rebalancing renin-angiotensinaldosterone system (raas) (might reduce the pulmonary inflammatory response and mortality) covid-19 patients, shang et al. reported that corticosteroid therapy and gamma globulin administration increased mortality and appeared to be useful only in patients with lower lymphocyte counts (6). according to the mentioned clinical reports, the administration of corticosteroids for covid-19 patients is still questionable. 3.2. case reports so far, there are three published case reports on the successful treatment of patients with covid-19. in the first report lim et al. described a 54-year-old man with covid-19 who was treated with lopinavir/ritonavir from day 10 of illthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e29 ness, 2 tablets (lopinavir 200mg / ritonavir 50mg) every 12 hours. since first day of administration, β-coronavirus viral load started to decrease, and little or no detectable coronavirus titers have been observed since then (7). in another case report, zhang et al. described a couple who were both 38 years old and were suffering from covid-19. their treatment included methylprednisolone 40 mg daily intravenous (iv ) injections for one and five days for the male and the female patient respectively, human gamma globulin 10g iv qd for five and seven successive days for the male and the female patient, respectively, and then the dose was changed to 5g for both of them, in addition to moxifloxacin, oseltamivir, arbidol hydrochloride, and tanreqing (chinese patent medicine). after 11 days, the female patient and after 14 days the male patient recovered with regards to inflammatory factors and were discharged from the hospital (8). in the third case report, chen et al. reported a 45-year-old woman with covid-19 and stated that after treatment with thalidomide (100 mg orally once a day) and methylprednisolone (40 mg intravenously bid for 3 days then reduced to once a day for 5 days) the overall patient status was improved, oxygen index was increased, symptoms of nausea and vomiting were alleviated, and cytokine levels were decreased (9). 3.3. potential drugs several articles have suggested medicines, potentially effective for the treatment of covid-19 (table 1). most of these suggestions are based on in vitro studies, virtual screenings and records of their effects on sars and mers. in addition to these medications, tocilizumab has recently been suggested as a covid-19 treatment. studies have shown that il-6 levels significantly correlated with the severity of covid-19, c-reactive protein (crp), lactate dehydrogenase (ldh), and d-dimer levels and t cell counts, and it has been suggested that tocilizumab, with its inhibitory effect on il-6, may be effective in treatment of covid-19 (10, 11). however, no clinical study has demonstrated the effects of tocilizumab on covid-19 and further studies are indeed required. 4. conclusion apparently, in addition to the drugs currently prescribed to treat covid-19, arbidol hydrochloride, interferon, and thalidomide plus methylprednisolone can also be used due to their effects reported in clinical studies. however, more studies are needed to confirm the use of corticosteroids, as there are conflicting reports regarding their efficacy. also, potential drugs listed in table 1, such as remdesivir, atazanavir, saquinavir, and formoterol, and tocilizumab can be introduced as treatments for covid-19 if they prove to be effective in animal and clinical studies. 5. declarations 5.1. funding support none. 5.2. conflict of interest none. references 1. zhou p, yang x-l, wang x-g, hu b, zhang l, zhang w, et al. discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. biorxiv. 2020. 2. gao j, tian z, yang x. breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid-19 associated pneumonia in clinical studies. bioscience trends. 2020. 3. jian-ya g. clinical characteristics of 51 patients discharged from hospital with covid-19 in chongqing, china. medrxiv. 2020. 4. qin x, qiu s, yuan y, zong y, tuo z, li j, et al. clinical characteristics and treatment of patients infected with covid-19 in shishou, china. china (february 18, 2020). 2020. 5. zhou z-g, xie s-m, zhang j, zheng f, jiang d-x, li ky, et al. short-term moderate-dose corticosteroid plus immunoglobulin effectively reverses covid-19 patients who have failed low-dose therapy. 2020. 6. shang j, du r, lu q, wu j, xu s, ke z, et al. the treatment and outcomes of patients with covid-19 in hubei, china: a multi-centered, retrospective, observational study. 2020. 7. lim j, jeon s, shin h-y, kim mj, seong ym, lee wj, et al. case of the index patient who caused tertiary transmission of covid-19 infection in korea: the application of lopinavir/ritonavir for the treatment of covid-19 infected pneumonia monitored by quantitative rt-pcr. journal of korean medical science. 2020;35(6). 8. zhang z, li x, zhang w, shi z-l, zheng z, wang t. clinical features and treatment of 2019-ncov pneumonia patients in wuhan: report of a couple cases. virologica sinica. 2020:1-7. 9. chen c, qi f, shi k, li y, li j, chen y, et al. thalidomide combined with low-dose glucocorticoid in the treatment of covid-19 pneumonia. 2020. 10. liu t, zhang j, yang y, zhang l, ma h, li z, et al. the potential role of il-6 in monitoring coronavirus disease 2019. medrxiv. 2020. 11. diao b, wang c, tan y, chen x, liu y, ning l, et al. reduction and functional exhaustion of t cells in patients with coronavirus disease 2019 (covid-19). medrxiv. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rismanbaf 4 12. wang m, cao r, zhang l, yang x, liu j, xu m, et al. remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-ncov ) in vitro. cell research. 2020;30(3):269-71. 13. zhang j, ma x, yu f, liu j, zou f, pan t, et al. teicoplanin potently blocks the cell entry of 2019-ncov. biorxiv. 2020. 14. xu z, peng c, shi y, zhu z, mu k, wang x, et al. nelfinavir was predicted to be a potential inhibitor of 2019ncov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation. biorxiv. 2020. 15. liu x, wang x-j. potential inhibitors for 2019-ncov coronavirus m protease from clinically approved medicines. biorxiv. 2020. 16. ton a-t, gentile f, hsing m, ban f, cherkasov a. rapid identification of potential inhibitors of sars-cov-2 main protease by deep docking of 1.3 billion compounds. chemrxiv; 2020. 17. jin z, du x, xu y, deng y, liu m, zhao y, et al. structure-based drug design, virtual screening and highthroughput screening rapidly identify antiviral leads targeting covid-19. biorxiv. 2020. 18. sekhar t. virtual screening based prediction of potential drugs for covid-19. 19. contini a. virtual screening of an fda approved drugs database on two covid-19 coronavirus proteins. 2020. 20. wang j. fast identification of possible drug treatment of coronavirus disease-19 (covid-19) through computational drug repurposing study. 2020. 21. wang q, zhao y, chen x, hong a. virtual screening of approved clinic drugs with main protease (3clpro) reveals potential inhibitory effects on sars-cov-2. 2020. 22. chen yw, yiu c-p, wong k-y. prediction of the 2019-ncov 3c-like protease (3clpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. chemrxiv; 2020. 23. beck br, shin b, choi y, park s, kang k. predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-ncov ), wuhan, china through a drug-target interaction deep learning model. biorxiv. 2020. 24. elfiky aa, ibrahim ns. anti-sars and anti-hcv drugs repurposing against the papain-like protease of the newly emerged coronavirus (2019-ncov ). 2020. 25. arya r, das a, prashar v, kumar m. potential inhibitors against papain-like protease of novel coronavirus (sarscov-2) from fda approved drugs. 2020. 26. smith m, smith jc. repurposing therapeutics for covid-19: supercomputer-based docking to the sarscov-2 viral spike protein and viral spike protein-human ace2 interface. 2020. 27. li z, bai t, yang l, hou x. discovery of potential drugs for covid-19 based on the. 28. richardson p, griffin i, tucker c, smith d, oechsle o, phelan a, et al. baricitinib as potential treatment for 2019-ncov acute respiratory disease. the lancet. 2020;395(10223):e30-e1. 29. nowak jk, walkowiak j. is lithium a potential treatment for the novel wuhan (2019-ncov ) coronavirus? a scoping review. f1000research. 2020;9(93):93. 30. sun m, yang j, sun y, su g. inhibitors of ras might be a good choice for the therapy of covid-19 pneumonia. zhonghua jie he he hu xi za zhi= zhonghua jiehe he huxi zazhi= chinese journal of tuberculosis and respiratory diseases. 2020;43:e014. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methodology results conclusion declarations references emergency. 2018; 6 (1): e9 ca s e re p o rt methamphetamine-induced cardiomyopathy (macm) in a middle-aged man; a case report zulfiqar qutrio baloch1∗, muhammad hussain2, shabber agha abbas2, jorge l. perez1, muhammad ayyaz1 1. department of internal medicine, brandon regional hospital, brandon, florida, usa. 2. r-endocrinology, hamilton, new jersey, usa. received: december 2017; accepted: december 2017; published online: 20 january 2018 abstract: the development of methamphetamine-associated cardiomyopathy (macm) represents a severe complication of chronic methamphetamine abuse. macm-induced irreversible structural and functional changes in the heart can eventually lead to decompensated heart failure, ultimately requiring heart transplantation. in this case report we present a 47-year old male with a previous history of chronic amphetamine abuse who presented to the emergency room with severe dyspnea at rest associated with mild substernal non-radiating chest pain. he denied any previous cardiac history but had a positive urinary toxicology for methamphetamine. a complete cardiac workup ruled out all other etiologies. the patient required a 3-week intensive pharmacotherapy intervention to stabilize acute heart failure symptoms. at discharge he was classified as having new york association class iii (nyha-iii) heart failure. his medical symptoms did not improve and he was considered for heart transplantation. with the increase in availability and abuse of methamphetamine, case of macm such as ours are more frequently being encountered in the emergency departments. in addition to raising awareness, our case provides an outline of how macm patients likely may present and the subsequent morbid sequela. clinicians should maintain a high degree of suspicion when assessing all patients with a history of methamphetamine abuse. early cardiac evaluation can help identify ventricular compromise in asymptomatic patients providing an opportunity to intervene prior to the development of irreversible macm. keywords: methamphetamine; cardiomyopathies; emergency service, hospital © copyright (2018) shahid beheshti university of medical sciences cite this article as: qutrio baloch z, hussain m, agha abbas sh, l. perez j, ayyaz m. methamphetamine-induced cardiomyopathy (macm) in a middle-aged man; a case report. emergency. 2018; 6 (1): e9. 1. introduction methamphetamine is a highly addictive central nervous system (cns) stimulant produced from the parent compound amphetamine, which is frequently used to treat attention deficit hyperactivity disorder. methamphetamine and related compounds are frequently abused as recreational drugs, and are the second most widely used illicit drug in the united states after cannabis (1). apart from cns stimulation, methamphetamine has significant adverse effects on the peripheral nervous system associated with both short-term and long-term usage. the primary mechanism of action of methamphetamine is the increased release and decreased ∗corresponding author: zulfiqar qutrio baloch, md, pgy 2, department of internal medicine, brandon regional hospital, 119 oakfield dr, brandon, fl 33511, usa. email: zulfiqar.qutrio@gmail.com tel: 813-916-5551, fax: 813916-2944 uptake of catecholamines at the neuronal synapse producing a marked effect on the cardiovascular system. common physical symptoms after acute intoxication are chest pain, hypertension, arrhythmias, myocardial infarction, and palpitations (2). chronic methamphetamine abuse can lead to development of severe cardiovascular complications such as coronary artery disease, acute myocardial infarction, ischemic cardiomyopathy, methamphetamine-associated cardiomyopathy (macm), aortic dissection, malignant hypertension, dysrhythmias, and sudden cardiac death (3, 4). we discuss the case of a patient with dyspnea at rest due to severe cardiomyopathy following three years of methamphetamine use. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com z. qutrio baloch et al. 2 2. case presentation: a 47-year-old male presented to the emergency department with a chief complaint of severe dyspnea at rest associated with mild substernal non-radiating chest pain. he denied palpitations, productive cough, abnormal sound while breathing, difficulty swallowing, history of a cardiac problem, recent viral illness, recent travel history, or any recent exposure to anyone having a similar presentation. his past medical and surgical histories were not significant. family history was not significant for cardiomyopathy. upon urinary drug screening his test was positive for methamphetamine use. he stated that he had been using methamphetamine for the past three years. he denied use of any other recreational drugs and denied excessive alcohol use. on physical examination he was found to be alert and oriented to time, place, and person. vital signs on presentation were: blood pressure: 90/70 mmhg, pulse rate: 120 beats/minute, and respiratory rate: 26 breaths/minute. arterial oxygen saturation was 88% in room air. examination of the chest revealed bilateral diffuse crackles, most pronounced on lung bases. a chest radiograph showed pulmonary congestion and cardiomegaly. an electrocardiogram (ecg) showed sinus tachycardia, low voltage, poor progression of r-wave in precordial leads, incomplete lbbb, extreme right axis deviation with rv strain, s1 q3 inverse t3 pattern, q-wave in 2-3 avf suggestive of old mi (figure 1). cardiac troponin testing was within reference range. to further narrow down the differential diagnosis a complete work-up was ordered including: complete blood count (cbc), basic metabolic profile (bmp), lipid profile, thyroid function tests, creatinine phosphokinase, erythrocyte sedimentation rate (esr), blood morphology, liver function test (lft), protein level, and iron studies. these were all found to be within reference range. moreover, immunological assays [immunoglobulin m (igm) and immunoglobulin g (igg) anti-epstein–barr virus] and toxoplasmosis serology were found to be negative. fasting transferrin saturation test was normal. transthoracic echocardiography (tte) revealed severe left ventricular (lv ) and left atrial (la) dilatation, extremely impaired systolic function with left ventricular ejection fraction (lvef) below 15% (actual was 8%), full size rv, normal mitral and aortic valve, normal aortic root size (figure 2). subsequent coronary angiography testing found no coronary artery disease. treatment for acute heart failure exacerbation was immediately initiated including use of lisinopril, carvedilol, and furosemide. following three weeks of intensive pharmacotherapy and considerable clinical improvement the patient was discharged from the hospital. at time of discharge the patient was classified as having new york heart association class iii (nyha-iii) heart failure. outpatient follow-up visits figure 1: 12 leads electrocardiography of the patient. figure 2: transthoracic echocardiography of the patient (parasternal long axis view). were scheduled at 1, 2, and 3 months, respectively. no clinical or echocardiographic improvements were noted during all follow-up visits. after optimal medical treatment the patient’s symptoms were not improved and he was considered for heart transplantation. 3. discussion the incidence of methamphetamine abuse among young population has increased with predominance among college students in the united states (5). there are several reasons behind this increased frequency. one explanation is the relatively easy availability and access through the internet as depicted in the world drug report 2016 (1). another reason is the inexpensive pricing making it a suitable drug of choice even for those with economic constraints. as an agent having a long duration of action it holds a particular appeal for those desiring chronic stimulant effects (1). methamphetamine can be ingested orally, smoked, snorted, or injected. smoking or injecting the drug produces an immediate effect and makes the patient prone to developing adverse health problems, while raising the addiction potential. methamphetamine has good lipid solubility compared to its parent compound, amphetamine, and can this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e9 more readily cross the blood brain barrier. the drug has a marked effect on both central and peripheral nervous systems. by facilitating increased release and decreased reuptake of catecholamines from nerve terminals, it stimulates alphaand beta-adrenergic receptors. the pronounced effects of the drug are on multiple organ systems including the cardiovascular system leading to hypertension and tachycardia in the short-term and severe cardiovascular complications such as myocardial infarction, dysrhythmias, ventricular hypertrophy, pulmonary edema, hypertension, cerebral stroke, cerebral hemorrhage, seizures, psychosis, and in certain cases even death. acute coronary syndrome can also be a result of cardiac damage as evident by published case reports on acute coronary syndrome and coronary artery rupture following drug abuse (6, 7). the prevalence of methamphetamine-induced heart failure is also considerable, with at least one study reporting an up to 5% incidence rate in patients presenting to the emergency department with heart failure (8). a recent article pointed out that the experience of emergency health care personnel, especially mental health professionals, in dealing with patients presenting with acute methamphetamine abuse is quite complex. they have to employ a range of different strategies to stabilize patients who are acutely engaged in hyperactive and stimulant behavior (9). the development of cardiomyopathy is a severe complication of chronic methamphetamine abuse and is rarely a sign of acute abuse. in a study on 107 young patients presenting with idiopathic cardiomyopathy, 40% of patients were found to have chronically abused methamphetamines in subsequent interviews and urinalyses (3). our patient presented with severe dyspnea at rest and on further investigation was found to have severe systolic dysfunction due to cardiomyopathy following three years of chronic methamphetamine abuse. patients fitting this profile develop structural and functional changes in myocytes such as atrophy, hypertrophy, eosinophilic degeneration, and fibrosis (10). histopathological assessment is likely to reveal cardiomyopathic lesions including slight interstitial fibrosis. these changes eventually lead to decompensated heart failure that requires heart transplantation for continued survival (8). certain patients who achieve symptomatic relief with pharmacotherapy alone may benefit from biventricular cardiac pacing or automatic implantable cardiac defibrillators (4). the decision to pursue such interventions depends on many factors such as treatment compliance, likelihood of relapse, presence of co-morbidities, and risk of device infection, especially in intravenous drug abusers (4). schurer and colleagues recently investigated the histopathological impact of methamphetamine discontinuation in chronic abuse patients by following the clinical characteristics, histopathological features, and clinical outcome in a cohort of 30 patients presenting with macm (10). patients with lvef <40%, whose endomyocardial biopsy confirmed macm were followed for mean 35 ± 22 months post-study inclusion. they compared histopathology changes between those who discontinued the drug and those who continued. patients enrolled in the study were highly symptomatic and 83.3% of them had new york heart association functional class iii or iv dyspnea. the mean duration of methamphetamine abuse was 5.7 years. baseline lvef was 19 ± 6%. at follow-up, 23 patients had stopped taking methamphetamine whereas 7 continued. those who continued had persistently, severely impaired lvef and lv dilatation; whereas those who discontinued had lv remodeling and improved lvef. discontinuation was also associated with improved symptoms. in terms of the primary endpoint of composite death, nonfatal stroke, and rehospitalization for heart failure, these events occurred more frequently in the group that continued abusing methamphetamine (p=0.037). with respect to histopathologic changes, only fibrosis was found to be associated with the duration of methamphetamine abuse, occurring in a more severe form with longer abuse duration. no difference in inflammatory changes was observed between the 2 groups. our patient had an lvef of 8%, which is typical as patients with macm have a significantly lower lvef compared to patients with cardiomyopathy from all other causes (3). in addition to that, our patient had no significant risk factors responsible for causing cardiomyopathy and heart failure, except for methamphetamine abuse. patients with a modestly reduced lvef may demonstrate a more severe ventricular dilatation than those with other causes of cardiomyopathy on imaging. macm and its clinical sequela warrant attention, especially in an era of increasing use of methamphetamines and related compounds. recognizing macm and associated heart failure in the emergency setting is essential for initiating both short-term and long-term treatments, which hold implications for survival. 4. conclusion: methamphetamine-induced cardiomyopathy or macm and its clinical sequela warrant attention, especially in an era of increasing use of methamphetamines and related compounds. clinicians should maintain a high degree of suspicion when assessing all patients with a history of methamphetamine abuse, especially chronic users and those who may have preliminary signs or symptoms of cardiovascular compromise. in patients presenting with idiopathic cardiomyopathy, methamphetamine abuse should be in the differential diagnosis if the patient’s profile is suspicious. early cardiac evaluation can identify ventricular compromise in asymptomatic patients prior to the development of macm and should be considered for screening purposes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com z. qutrio baloch et al. 4 5. appendix 5.1. acknowledgements the authors would like to thank the internal medicine department staff of brandon regional hospital, brandon, florida, usa. 5.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest none. 5.4. funding none. references 1. world drug report 2016 [cited 2017 august 28]. available from: http://www.unodc.org/doc/wdr2016/ world_drug_report_2016_web.pdf. 2. lan k-c, lin y-f, yu f-c, lin c-s, chu p. clinical manifestations and prognostic features of acute methamphetamine intoxication. journal of the formosan medical association= taiwan yi zhi. 1998;97(8):528-33. 3. yeo k-k, wijetunga m, ito h, efird jt, tay k, seto tb, et al. the association of methamphetamine use and cardiomyopathy in young patients. the american journal of medicine. 2007;120(2):165-71. 4. paratz ed, cunningham nj, macisaac ai. the cardiac complications of methamphetamines. heart, lung and circulation. 2016;25(4):325-32. 5. mccabe se, knight jr, teter cj, wechsler h. nonmedical use of prescription stimulants among us college students: prevalence and correlates from a national survey. addiction. 2005;100(1):96-106. 6. brennan k, shurmur s, elhendy a. coronary artery rupture associated with amphetamine abuse. cardiology in review. 2004;12(5):282-3. 7. pozoga j, snopek g, dabrowski m. acute coronary syndrome after amphetamine use in a young male with myocardial bridging–a case report. kardiologia polska. 2005;62(4):381-2. 8. diercks db, fonarow gc, kirk jd, jois-bilowich p, hollander je, weber je, et al. illicit stimulant use in a united states heart failure population presenting to the emergency department (from the acute decompensated heart failure national registry emergency module). the american journal of cardiology. 2008;102(9):1216-9. 9. cleary m, jackson d, woods c, kornhaber r, sayers j, usher k. experiences of health professionals caring for people presenting to the emergency department after taking crystal methamphetamine (“ice”). issues in mental health nursing. 2017;38(1):33-41. 10. schurer s, klingel k, sandri m, majunke n, besler c, kandolf r, et al. clinical characteristics, histopathological features, and clinical outcome of methamphetamineassociated cardiomyopathy. jacc: heart failure. 2017;5(6):435-45. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com archives of academic emergency medicine. 2020; 8(1): e42 br i e f re p o rt one-month outcomes of cases receiving ticagrelor after percutaneous coronary intervention; a case series mohammad hasan namazi1, farzam saemifard1, mehdi pishgahi2∗ 1. interventional cardiology department, shahid modarres heart center, shahid beheshti university of medical sciences, tehran, iran. 2. interventional cardiology department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2020; accepted: february 2020; published online: 30 march 2020 abstract: introduction: ticagrelor is the first reversibly binding oral p2y12 receptor antagonist that can block adpinduced platelet aggregation. this study aimed to describe one-month follow-up findings of cases undergoing ticagrelor therapy after percutaneous coronary intervention (pci). methods: this case series was performed on acute coronary syndrome (acs) patients who were candidates for pci and received aspirin plus ticagrelor after pci. patients were followed for one month and their outcomes were described. results: 156 cases with the mean age of 59.74 ± 9.24 years were studied (63% male). 45 (28.8%) cases complained of dyspnea (39 cases with mild and 6 cases with severe dyspnea). bleeding occurred in 4 (2.5%) cases (intra-cranial hemorrhage (ich) in one, hematuria in two, and skin hemorrhage in one case). there were no cases with bradycardia or thrombosis. one (0.6%) patient developed drug hypersensitivity reaction, which manifested as skin rash. the use of drug was stopped in 10 (6.4%) cases due to severe dyspnea (n= 6), ich (n=1), skin rash (n=1), and concomitant left ventricular (lv ) clot (n=2). conclusion: the most important finding of one-month ticagrelor consumption were dyspnea, bleeding, and hypersensitivity reaction. no case of bradycardia and stent thrombosis was detected. in our study, iranian population has more susceptibility to dyspnea than plato result. the rate of drug discontinuation in this series of cases was 6.4%. keywords: ticagrelor; patient outcome assessment; drug-related side effects and adverse reactions; percutaneous coronary intervention; platelet aggregation inhibitors cite this article as: namazi m h, saemifard f, pishgahi m, heydari k, sohrabi s. one-month outcomes of cases receiving ticagrelor after percutaneous coronary intervention; a case series. arch acad emerg med. 2020; 8(1): e42. 1. introduction antiplatelet and anti-coagulants are used to prevent stent thrombosis and repeated acute coronary events in patients undergoing primary percutaneous coronary intervention (ppci) (1, 2). according to existing guidelines, rather than using clopidogrel (p2y12), prescription of more potent agents from this family, such as ticagrelor is recommended (3, 4). ticagrelor is a potent drug with class i of recommendation for acute coronary syndrome (acs) patients (5). possible adverse effects include bleeding and dyspnea, which are mainly mild and do not require intervention (6, 7). ticagrelor is the first reversibly binding oral p2y12 receptor antagonist that can block adp-induced platelet aggrega∗corresponding author: mehdi pishgahi; interventional cardiology department, shohadaye tajrish hospital, tajrish square, tehran, iran. tel: 00989123387486, email: mpishgahi.cr@gmail.com tion (8). unlike thienopyridines, which irreversibly binds to p2y12 receptor throughout the platelet’s lifetime, ticagrelor can bind to the receptor reversibly and exhibits a rapid onset and offset of effect, corresponding to drug exposure levels (4, 9). since this drug has recently been introduced in pharmacies in iran and there are no studies on its adverse effects such as bleeding, dyspnea, bradycardia, and etc. (10). this study aimed to describe the one-month follow-up findings of cases that underwent ticagrelor therapy after percutaneous coronary intervention (pci). 2. methods 2.1. study design and setting this case series was performed on acs patients who were candidates for ppci and were referred to the emergency department of modarres hospital, tehran, iran, from september 2018 to september 2019 (one year). based on the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m h. namazi et al. 2 hospital protocol, aspirin plus clopidogrel or aspirin plus ticagrelor were prescribed for patients as anti-platelet aggregation agents. in the present study, one-month outcomes of cases that consumed aspirin plus ticagrelor are described. the study protocol was approved by local ethics committee of modarres hospital and also ethics committee of shahid-beheshti university of medical sciences (code: ir.sbmu.mcp.rec.1397.602). 2.2. participants acs patients who were candidates for ppci and consumed aspirin plus ticagrelor were enrolled using consecutive sampling. patients with end-stage renal disease (esrd), sensitivity to the studied drugs, history of coagulation disorders and history of fibrinolytic therapy in the past 48 hours were excluded. patients received aspirin plus ticagrelor loading dose (180 mg; brilinta from astrazeneca co.) with maintenance of 90 mg ticagrelor twice a day plus 80 mg asa daily. they were followed-up for one month monitoring possible complications. 2.3. data analysis data analysis was carried out using spss (version 19.0) software. the numerical data were presented as mean ± standard deviation and categorical ones were shown as frequency and percentage. 3. results 3.1. baseline characteristics of studied cases 156 cases with the mean age of 59.74 ± 9.24 (ranging 37 to 78) years were studied (63% male). st segment elevation myocardial infarction (stemi) (42%), unstable angina (36%), and non-stemi (22%) were the most common diagnoses, respectively. diabetes mellitus (34%) and hypertension (28%) were the most frequent underlying diseases of studied cases. 3.2. outcomes 45 (28.8%) cases complained of dyspnea (39 cases with mild and 6 cases with severe dyspnea). bleeding occurred in 4 (2.5%) cases (intra-cranial hemorrhage (ich) in one, hematuria in two, and skin hemorrhage in one case). there were no cases with bradycardia or thrombosis. one (0.6%) patient developed drug hypersensitivity reaction, which manifested as skin rash. the use of drug was stopped in 10 (6.4%) cases due to severe dyspnea (n= 6), ich (n=1), skin rash (n=1), and concomitant left ventricular (lv ) clot (n=2). 4. discussion the most important findings after one month of ticagrelor consumption in this series were dyspnea (28.8%), bleeding (2.5%), and hypersensitivity reaction (0.6%). no case of bradycardia and stent thrombosis was detected. the rate of drug discontinuation in this series of cases was 6.4%. ticagrelor has potential to change the standard of drug therapy for acs patients as shown in platelet inhibition and patient outcomes (plato) trial, but long-term studies are required to further evaluate its efficacy and safety in these patients (11). ticagrelor is the first reversibly binding oral p2y12 receptor antagonist that blocks adp-induced platelet aggregation (12). risk of mild to moderate dyspnea and mostly asymptomatic ventricular pauses were observed in phase ii trials of ticagrelor (13). in plato study, at 12 months, the primary end point included death from vascular causes, myocardial infarction, or stroke, which had occurred in 9.8% of patients receiving versus 11.7% of those receiving clopidogrel (14). however, there were no positive thrombotic cases in our study. additionally, in plato study (15), ticagrelor showed a higher rate of major bleeding, which was not related to the procedure, compared to clopidogrel. ticagrelor caused significantly more instances of fatal intracranial bleeding, but fewer fatal bleeding of other types. in our study, there was only one case with intracranial bleeding. the study by levin et al. (16) showed improved survival and reduction in major cardiovascular events with ticagrelor consumption. kang et al. (17) reported that cardiovascular event rates are higher in asians, but bleeding rates are similar and, the effects of ticagrelor versus clopidogrel are not significantly different between asians and non-asians with respect to the primary outcome and efficacy. overall, this study revealed that ticagrelor is an effective drug but it should be used with caution as there are major concerns regarding its side effects such as severe dyspnea and major bleeding events, which have also been observed with clopidogrel consumption. however, further studies with larger sample sizes are required to attain more definitive results and precisely determine its efficacy and safety. 5. conclusion the most important findings of one month ticagrelor consumption in this series were dyspnea (28.8%), bleeding (2.5%), and hypersensitivity reaction (0.6%). no case of bradycardia and stent thrombosis was detected. in our study, iranian population has more susceptibility to dyspnea than plato result. the rate of drug discontinuation in this series of cases was 6.4%. 6. declarations 6.1. acknowledgements the authors express their sincere thanks to the staff of modarres hospital, tehran, iran for their assistance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e42 6.2. author contribution all the authors met the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids mohammad hasan namazi: 00000001-5801-9925 mehdi pishgahi: 0000-0002-1196-6535 6.3. funding none. 6.4. conflict of interest the authors declare that there is no conflict of interest. references 1. park j, min j, kang j, in y. acute myocardial infarction due to stent thrombosis after administration of intravenous epinephrine for anaphylaxis. chinese medical journal. 2015;128(19). 2. tyczynski p, karcz ma, kalinczuk k, fronczak a, witkowski a. early stent thrombosis. aetiology, treatment, and prognosis. postepy w kardiologii interwencyjnej= advances in interventional cardiology. 2014;10(4):221. 3. rademakers l, dewilde w, van de kerkhof d. early double stent thrombosis associated with clopidogrel hyporesponsivenesss. netherlands heart journal. 2012;20(1):3841. 4. olechowski b, ashby a, sambu n, mahmoudi m, curzen n. stent thrombosis patients with hyporesponsiveness to clopidogrel, prasugrel, and ticagrelor: a case series using short thromboelastography. case reports in medicine. 2016;2016. 5. jariwala p, bhatia h, kumar eap. sub-acute stent thrombosis secondary to ticagrelor resistance–myth or reality!! indian heart journal. 2017;69(6):804. 6. fan z-g, zhang w-l, xu b, ji j, tian n-l, he s-h. comparisons between ticagrelor and clopidogrel following percutaneous coronary intervention in patients with acute coronary syndrome: a comprehensive meta-analysis. drug design, development and therapy. 2019;13:719. 7. volney c, collins a, adams s. ticagrelor versus clopidogrel in the management of acute myocardial infarction. journal of community hospital internal medicine perspectives. 2019;9(4):314-8. 8. husted s, van giezen j. ticagrelor: the first reversibly binding oral p2y12 receptor antagonist. cardiovascular therapeutics. 2009;27(4):259-74. 9. dimitrova g, tulman d, bergese s. perioperative management of antiplatelet therapy in patients with drugeluting stents. hsr proceedings in intensive care & cardiovascular anesthesia. 2012;4(3):153. 10. akhlaghi a, shirani s, ziaie n, pirhaji o, yaran m, shahverdi g, et al. cytochrome p450 2c19 polymorphism in iranian patients with coronary artery disease. arya atherosclerosis. 2011;7(3):106. 11. reejhsinghani r, lotfi as. prevention of stent thrombosis: challenges and solutions. vascular health and risk management. 2015;11:93. 12. bergmeijer to, van oevelen m, janssen pw, godschalk tc, lichtveld ra, kelder jc, et al. safety of ticagrelor compared to clopidogrel after prehospital initiation of treatment. th open. 2018;2(04):e357-e68. 13. goel d. ticagrelor: the first approved reversible oral antiplatelet agent. international journal of applied and basic medical research. 2013;3(1):19. 14. wallentin l, becker rc, budaj a, cannon cp, emanuelsson h, held c, et al. ticagrelor versus clopidogrel in patients with acute coronary syndromes. new england journal of medicine. 2009;361(11):1045-57. 15. wallentin l, james s, storey rf, armstrong m, barratt bj, horrow j, et al. effect of cyp2c19 and abcb1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the plato trial. the lancet. 2010;376(9749):1320-8. 16. levin l-a, wallentin l, bernfort l, andersson d, storey rf, bergstrãűm g, et al. health-related quality of life of ticagrelor versus clopidogrel in patients with acute coronary syndromes–results from the plato trial. value in health. 2013;16(4):574-80. 17. kang h-j, clare rm, gao r, held c, himmelmann a, james sk, et al. ticagrelor versus clopidogrel in asian patients with acute coronary syndrome: a retrospective analysis from the platelet inhibition and patient outcomes (plato) trial. american heart journal. 2015;169(6):899-905. e1. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 107 emergency (2014); 2 (3): 107-114 original research the effects of air pollution on cardiovascular and respiratory causes of emergency admission ali mohammad shahi1, ali omraninava1, mitra goli2, hamid reza soheilarezoomand3, nader mirzaei1* 1. department of emergency medicine, aja university of medical sciences, tehran, iran 2. department of geriatric nursing, university of social welfare and rehabilitation sciences, tehran, iran 3. department of environmental health engineering, school of public health, tehran university of medical sciences, tehran, iran abstract introduction: today, air pollution is one of the critical problems in metropolitans and necessary preparations are needed for confronting this crisis. the present study was based on the goal of determining the relationship of air pollutant levels with the rate of emergency admissions for respiratory and cardiovascular patients. methods: in the present retrospective cross-sectional study, all respiratory and cardiovascular patients, referred to emergency department during 2012, were assessed. the meteorological and air pollution data were collected. information regarding the numbers and dates (month, day) of admission for respiratory and cardiovascular diseases was achieved from the hospital's electronic registration system. the relation of air pollution and respiratory and cardiovascular admissions were analyzed by generalize additive model (gam). results: 5922 patients were assessed which included 4048 (68.36%) cardiovascular and 1874 (31.64%) respiratory. carbon monoxide (co) level was an independent risk factor of cardiovascular disease on the same day (rr=1.49; 95% ci: 1.251.77; p<0.001), the day before (rr=1.22; 95% ci: 1.021.45; p=0.03), and the last two days (rr=1.3; 95% ci: 1.09 1.54; p<0.001). the same process was repeated for ozone (o3). in addition, the o3 level on the same day (rr=1.49; 95% ci: 1.251.77; p<0.001), the day before (rr=1.22; 95% ci: 1.021.45; p=0.03), the last two days (rr=1.3; 95% ci: 1.091.54; p<0.001), and the last week (rr=1.004; 95% ci: 1.0007-1.008; p=0.02) were independent risk factors of respiratory admissions. the increased level of particulate matter less than 2.5 micrometers in diameter (pm2.5) like o3 led to growth in the admissions to emergency department. conclusion: the findings of the present study suggested that rising levels of co and o3 during two days leads to a significant increase in cardiovascular admission on the third day. furthermore, increase in o3, pm2.5, nitrogen dioxide (no2), and co levels causes a rise in respiratory admissions to emergency department. key words: air pollutant; patient admission; cardiovascular disease; respiratory disease cite this article as: mohammad shahi a, omraninava a, goli m, soheilarezoomand hr, mirzaei n. the effects of air pollution on cardiovascular and respiratory causes of emergency admission. emergency. 2014;2(3):107-14. introduction:1 ir pollution is a complicated and heterogeneous mixture of gases, liquids, and particulate matter (pm) which is known as one of the risk factors of cancers, respiratory and cardiovascular diseases (1-4). during the past 20 years, numerous epidemiologic reports have shown a growing concern related to possible dangerous effects of air pollution on cardiovascular diseases (5, 6). among these pollutants, more attention has been paid to carbon monoxide (co), nitrogen oxides (nox), sulfur oxide (so2), ozone (o3), lead, and thoracic particles such as particulate matter less than 10 mi *corresponding author: nader mirzaei; department of emergency medicine, aja university of medical sciences, bessat hospital, tehran, iran. tel/fax +982188028354; email: nad5406@yahoo.com received: may 2014; accepted: june 2014 crometers in diameter (pm10) and fine particles like particulate matter less than 2.5 micrometers in diameter (pm2.5) (7-10). the findings of these studies are representative of the direct relation between the levels of these molecules in the air and the rate of admission as well as mortality of cardiovascular diseases (11). therefore, the cardiac causes of mortality were exacerbated even with short-term increase in these components (12-14). however, little information has been achieved about the air pollution morbidity most of which relate to decades of 1990 and 2000. since the levels of so2, pm10, and pm2.5 have noticeably increased in recent years (15), further assessment of this relationship is highly important. a mailto:nad5406@yahoo.com this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com mohammad shahi et al 108 today, air pollution is recognized as a crisis in metropolitans and necessary preparations are required for confronting this problem. preparation of health care systems to control and treat diseases risen from air pollution is very significant in management of these patients. awareness of patient admissions has a remarkable role in providing proportional equipment and facilities fitted with the number of admitted patients. on the other hand, because of differences in pollutant levels of various geographical locations, the pattern of hospital admissions may have a noticeable difference on polluted days (16). therefore, it is critical for health care systems to be informed of the pattern of hospital admissions in polluted days to program more accurate man agent plan. the present study was done based on the goal of determining the relationship of air pollutant levels with the rate of emergency admissions for respiratory and cardiovascular patients. methods: study design and setting: in this retrospective crosssectional study, the association between air pollutant levels with respiratory and cardiovascular diseases has been evaluated in patients referred to the emergency department of bessat hospital, tehran, iran, during 2012. tehran, the capital of iran, is the most air-polluted city in this country and most of its pollution results from traffic and transport. about 8.5 million people live in this city and make up more than 10% of iran's population. patients the studied population were patients referred to the emergency department with diagnosis of non-traumatic cardiovascular and respiratory disease from april 2012 to april 2013. exclusion criterion was uncertainty of diagnosis. hospital admissions information of daily admissions of respiratory and cardiovascular diseases was achieved from hospital's electronic registration system. at first, the numbers and dates (month, day) of admissions were extracted. myocardial infarction, ischemic attacks, angina pectoris, coronary cardiovascular disease, cardiomyopathy, heart failure, cardiac dysrhythmia, endocarditis, and myocarditis were counted as cardiovascular disease. in addition, asthma, emphysema, allergies, bronchitis, obstructive pulmonary disease, respiratory infections, and table 1: the status of emergency admission and air pollutants during study period  variable mean±sd min centile 25 median centile 75 max emergency admission cardiac 11.06±2.05 5 10 11 12 16 respiratory 5.12±1.75 2 3 5 6 10 total 16.18±1.85 12 15 16 18 21 air pollutants concentrations co (µg/m3) 3.7±0.88 1.9 3 3.6 4.3 6.5 no2 (µg/m3) 47.58±11.68 18 38 47 56 78 o3 (µg/m3) 37.08±11.6 12 27 38 45 70 so2 (µg/m3) 32.22±4.67 20 29 32 35 50 pm2.5 (µg/m3) 98.77±23.9 42 83 95 110 192 pm10 (µg/m3) 64.72±19.49 24 42 62 71 201 meteorological measures temperature (°c) 19.6±9.43 -2 10.3 21.2 28.9 41.3 humidity (%) 48.97±15.28 20 40 50 60 79 wind speed (km/h) 17.7±5.55 10 13 17 22 34 sd: standard deviation; co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter. table 2: correlation matrix between air pollutants and meteorological variables  co o3 so2 no2 pm10 pm2.5 temperature wind speed humidity co 1.00 o3 0.05 1.00 so2 0.42a -0.05 1.00 no2 0.38 a 0.47 a 0.39 a 1.00 pm10 0.43 a 0.03 0.54 a 0.40 a 1.00 pm2.5 0.23 a 0.39 a 0.36 a 0.54 a 0.54 a 1.00 temperature -0.23 a -0.38 a 0.01 -0.32 a -0.04 -0.23 a 1.00 wind speed -0.14b -0.16b -0.06 -0.07 0.06 -0.04 0.42 a 1.00 humidity 0.12c 0.25 a -0.12c 0.17b -0.03 0.18 a -0.62 a -0.34 a 1.00 a: p<0.001; b: p<0.01; c: p<0.05; co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 109 emergency (2014); 2 (3): 107-114 pneumonia were considered as respiratory problems. air pollution and meteorological characteristics there are 31 air quality-monitoring stations in tehran city, recording data 24 hours per day. these stations check the levels of co, pm10, pm2.5, no2, o3, and so2 each hour. in the present study, these data were used to calculate the average of pollutant concentrations during 24 hours. it is worth noting that meteorology organization of tehran measures the average of humidity, temperature, and wind speed, hourly. there are 13 meteorology stations in the province five of which are specifically representative of meteorological situations of tehran city. the data of these five stations were extracted and used. statistical analysis descriptive statistics and correlation among emergency admissions, air pollutants, and meteorology factors (temperature, humidity, and wind speed) were analyzed using spss statistical software version 21.0. relative risks of respiratory and cardiovascular admissions were calculated by generalize additive model (gam) based on poisson distribution; because the previous studies showed that the distribution of pollutants’ data didn't follow the normal pattern (5, 6). each gam was fitted based on the logarithm of the emergency admission numbers as well as the overall adjusted and linear effects of predictive factors (air pollutants). therefore, smoothing spline functions were applied to temperature, wind speed, and humidity as confounding factors. degree of freedom was defined in terms of akaike’s criterion (17). the daily levels of pollutants for the same day (lag0), the average of the day before and same day (lag1), average of the last two days (lag2), and average of the last week (lag7) were analyzed and the association of pollutant levels with number of daily emergency admissions were evaluated in each period. all the findings were presented as relative risk (rr) and 95% confidence intervals (95% ci). in all analyses p<0.05 was defined as significance level. results: in the present study, the data of daily air pollutant levels, humidity, temperature, and wind speed during 2012 were collected. in total 5922 patients were assessed including 4048 (68.36%) cardiovascular and 1874 (31.64%) respiratory. the admission numbers of cardiovascular patients in winter was significantly lowtable 3: the correlation between enviromental pollutants and cardiovascular admissions in the studied hospital  variable adjusted relative risk 95% confidence interval pa lag 0 co 1.49 1.25-1.77 <0.001 o3 1.02 1.01-1.03 <0.001 no2 1.001 0.98-1.03 0.01 so2 0.998 0.97-1.03 0.94 pm10 0.99 0.98-1.01 0.41 pm2.5 1.004 0.99-1.02 0.53 lag 1 co 1.22 1.02-1.45 0.03 o3 1.01 1.001-1.02 0.03 no2 1.00 0.98-1.02 0.94 so2 0.99 0.96-1.02 0.64 pm10 0.98 0.98-1.01 0.06 pm2.5 1.01 0.99-1.02 0.35 lag 2 co 1.30 1.09-1.54 <0.001 o3 1.01 1.001-1.02 0.02 no2 0.99 0.96-1.01 0.25 so2 0.99 0.96-1.02 0.37 pm10 1.00 0.98-1.02 0.94 pm2.5 1.00 0.99-1.01 0.69 lag 7 co 0.97 0.88-1.08 0.60 o3 0.99 0.99-1.002 0.19 no2 1.01 0.99-1.02 0.13 so2 1.001 0.98-1.02 0.96 pm10 1.003 0.99-1.01 0.41 pm2.5 1.00 0.99-1.002 0.36 a: adjusted for temperature, wind speed, humidity and other air pollutants. co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com mohammad shahi et al 110 er than other seasons (10.3 admissions per day) (df: 3, 362; f=23.24; p=0.0007). the average humidity in the study period was 48.97±15.26 percent and the average of maximum wind speed was 17.7±5.55 kilometers per hour. the findings of this study revealed that with humidity increasing (r=0.35; p<0.001) the rate of respiratory diseases grew, while the wind speed had an inverse relation with admission numbers of respiratory patients (r=-0.16; p=0.002). the wind speed (r=0.097; p=0.06) and humidity (r=-0.06; p=0.23) did not have a significant correlation with cardiovascular admissions. table 1 shows the respiratory and cardiovascular admission status along with air pollutant levels during the study period. table 2 shows the correlation among air pollution indicators. based on this table, pm2.5 and no2 have a correlation with other pollutants. the strongest relationships were seen between pm10 and pm2.5 (r=0.54; p<0.001), no2 and pm2.5 (r=0.54; p<0.001), and no2 and o3 (r=0.47; p<0.001). all pollutant levels except pm10 have a significant relation with relative humidity. the air pollutant levels and cardiovascular emergency admissions the findings of the present study showed that cardiovascular admissions to emergency department have a significant association with increasing pollutant levels (figure 1 and table 3). after adjusting the analysis for season, temperature, wind speed, humidity, and other air pollutants, the co level on the same day (rr=1.49; 95% ci: 1.251.77; p<0.001), the day before (rr=1.22; 95% ci: 1.021.45; p=0.03), and the last two days (rr=1.3; 95% ci: 1.091.54; p<0.001) were independent risk factors of cardiovascular admissions. the same pattern was seen for o3. other air pollutants did not have any effects on cardiovascular admissions. the air pollutant levels and respiratory emergency admissions respiratory admissions to emergency department also had a significant relationship with increasing pollutant levels (figure 2 and table 4). after adjusting the analysis for season, temperature, wind speed, humidity, and other air pollutants, the o3 level on the same day table 4: the correlation between enviromental pollutants and respiratory admissions in the studied hospital  variable adjusted relative risk 95% confidence interval pa lag 0 co 1.04 1.002-1.09 0.04 o3 1.01 1.008-1.015 <0.001 no2 1.01 1.002-1.01 0.01 so2 0.99 0.985-1.00 0.05 pm10 0.998 0.996-1.001 0.33 pm2.5 1.002 1.001-1.004 0.01 lag 1 co 1.04 0.999-1.08 0.06 o3 1.005 1.002-1.009 <0.001 o3 1.002 0.998-1.006 0.24 no2 0.998 0.99-1.005 0.62 so2 0.999 0.996-1.002 0.62 pm10 1.002 1.0003-1.004 0.02 lag 2 co 1.04 1.001-1.085 0.04 o3 1.007 1.003-1.01 <0.001 no2 1.0004 0.996-1.005 0.84 so2 0.995 0.988-1.003 0.21 pm10 0.999 0.997-1.002 0.71 pm2.5 1.002 1.001-1.004 0.01 lag 7 co 1.03 0.99-1.07 0.14 o3 1.004 1.0007-1.008 0.02 no2 1.005 1.0006-1.009 0.03 so2 0.998 0.993-1.007 0.00 pm10 0.999 0.996-1.002 0.77 pm2.5 1.002 1.001-1.004 0.01 a: adjusted for temperature, wind speed, humidity and other air pollutants. co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 111 emergency (2014); 2 (3): 107-114 (rr=1.49; 95% ci: 1.251.77; p<0.001), the day before (rr=1.22; 95% ci: 1.021.45; p=0.03), the last two days (rr=1.3; 95% ci: 1.091.54; p<0.001), and the last week (rr=1.004; 95% ci: 1.0007-1.008; p=0.02) were independent risk factors of admission. increased level of pm2.5 led to a growth in the admissions to emergency department with respiratory causes just like o3. altered levels of no2 and so2 did not have any effects on respiratory admissions. discussion: the findings of the present study revealed that air pollutant levels have a direct relationship with the number of respiratory and cardiovascular admissions. the increased levels of no and o3 in the two days before admission, caused a significant increase in cardiovascular admissions. similarly, increased o3, pm2.5, co, and no2 levels were associated with more respiratory admissions to emergency. in several studies, co was mentioned as the most effective pollutant on hospital admissions. for example, in a study qorbani et al. showed that there is a significant relationship between acute coronary syndrome and the co level in tehran citizens. also, it was suggested that there was no correlation between the increased levels of pm10 and pm2.5 and coronary heart disease (7). hosseinpoor et al. displayed that the relative risk of angina figure 1: the relation between cardiovascular admissions and air pollutant levels. ** statistically significant at level of p<0.001; * statistically significant at level of p<0.05 co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com mohammad shahi et al 112 pectoris increased with higher co levels in the two days before admission. this group didn't find any associations between the rate of angina pectoris and other pollutants (11). furthermore, in this study co level had the closest relation with cardiovascular diseases with o3 in the second rank. although in some studies (7, 11), there was no association seen between o3 and emergencyadmissions with cardiovascular disease. destructive effects of these pollutants on cardiovascular system has been recognized since many years ago. for example, a review study showed that o3 was one of the most toxic components of mixed photochemical of air (14). thus, its increase in air resulting in more the hospital admissions is not too far-fetched. on the other hand, because of further urbanization of tehran, ozone level has remarkably increased in recent years. qorbani et al. (7) reported the average of ozone levels 9.7 µg/m3 in 2001, while in the present study, the annual average of this component was 37.08 µg/m3. although some studies revealed that short-term exposure to particulate matters, increases the risk for cardiovascular admission but the present study did not find any relationship between them. dominici et al. suggested that the levels of these pollutants are associated with increased cardiovascular admissions (18). in contrast, hosseinpoor et al (11) and chen et al (19) found no significant effects. this may be due to misclassification of the average population exposure to particulate matters (20). in addition, some stud figure 2: the relation between respiratory admissions and air pollutant levels. ** statistically significant at level of p<0.001; * statistically significant at level of p<0.05 co: carbon monoxide; no2: nitrogen oxide; o3: ozone; so2: sulfur oxide; pm2.5: like particulate matter less than 2.5 micrometers in diameter; pm10: like particulate matter less than 10 micrometers in diameter.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 113 emergency (2014); 2 (3): 107-114 ies have stated that biological variables such as ventilation, time spent outdoors, and household characteristics, affect the strength of these associations. so, for certain individuals and cohorts the health effects attributed to particulate matter might vary in different geographic areas (21). air pollution is one of the significant environmental risk factors of acute and chronic respiratory disease. the present project revealed that increased levels of o3, pm2.5, and co aligned with more emergency admissions due to respiratory diseases. the role of ozone in higher respiratory admissions arose from the effect of this pollutant on increasing inflammation in the respiratory tract (12) which is critical in respiratory disease symptoms. in addition, ozone reduces the respiratory function, increases the activity of respiratory tracts, and asthma. this component leads to increased emergency admissions with respiratory disease in adults and children (22). burnett and his colleagues showed that one hour increase in the ozone level during the last five days caused 35% increase in emergency admissions for children less than two years of age (12). ji et al. in their meta-analysis displayed that 10 parts-per-billion increase in ozone leads to 3% increase in respiratory causes of emergency referrals (15). lin et al. also revealed that there is a strong association between increased level of ozone and clinical admissions for respiratory diseases (6). pm2.5, like ozone, has a remarkable role in respiratory symptoms. dominici et al. showed that pm2.5 has a close association with increased emergency admissions because of obstructive lung diseases and lung infections (18). similarly, lall et al. suggested that there is an interconnection between pm2.5 level and emergency admissions for respiratory diseases (23). the present study showed similar results, too. there are several disagreements regarding the correlation between levels of other pollutants and respiratory emergency admissions. chen et al. presented that no2, pm10, and so2 levels don't have a correlation with respiratory diseases in shanghai, china (19). whereas tao et al. showed that a strong association exists between these three pollutants and respiratory diseases in lanzhou, china. this issue was raised due to the difference among pollutant levels in various urban areas. no2 had a significant relation with respiratory admissions in this study. conclusion: the findings of the present study suggested that raised levels of co and o3 during two days leads to a significant increase in cardiovascular admissions. furthermore, increased o3, pm2.5, no2, and co levels cause a rise in respiratory admissions to emergency department. acknowledgments: the authors appreciate the insightful cooperation of the staff in the emergency department of bessat hospital in tehran, iran. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. zhou m, liu y, wang l, kuang x, xu x, kan h. particulate air pollution and mortality in a cohort of chinese men. environ pollut. 2014;186:1-6. 2. beverland i, carder m, cohen g, heal m, agius r. associations between short/medium-term variations in black smoke air pollution and mortality in the glasgow conurbation, uk. environ int. 2014;62:126-32. 3. dimakopoulou k, samoli e, beelen r, et al. air pollution and nonmalignant respiratory mortality in 16 cohorts within the escape project. am j respir crit care med. 2014;189(6):68496. 4. masjedi mr, naghan pa, taslimi s, et al. opium could be considered an independent risk factor for lung cancer: a casecontrol study. respiration. 2013;85(2):112-8. 5. tao y, mi s, zhou s, wang s, xie x. air pollution and hospital admissions for respiratory diseases in lanzhou, china. environ pollut. 2014;185:196-201. 6. lin y-k, chang s-c, lin c, chen y-c, wang y-c. comparing ozone metrics on associations with outpatient visits for respiratory diseases in taipei metropolitan area. environ pollut. 2013;177:177-84. 7. qorbani m, yunesian m, fotouhi a, zeraati h, sadeghian s, rashidi y. relation between air pollution exposure and onset of acute coronary syndrome in tehran heart center using a case-crossover design. iran j epidemiol. 2007;3(1):53-9. 8. heo j, schauer jj, yi o, paek d, kim h, yid s-m. fine particle air pollution and mortality. epidemiology. 2014;25(3):37988. 9. moolgavkar sh, mcclellan ro, dewanji a, turim j, luebeck eg, edwards m. time-series analyses of air pollution and mortality in the united states: a subsampling approach. environ health perspect. 2013;121(1):73-8. 10. cesaroni g, badaloni c, gariazzo c, et al. long-term exposure to urban air pollution and mortality in a cohort of more than a million adults in rome. environ health perspect. 2013;121(3):324-31. 11. hosseinpoor ar, forouzanfar mh, yunesian m, asghari f, naieni kh, farhood d. air pollution and hospitalization due to angina pectoris in tehran, iran: a time-series study. environ res. 2005;99(1):126-31. 12. burnett rt, smith-doiron m, stieb d, et al. association between ozone and hospitalization for acute respiratory diseases in children less than 2 years of age. am j epidemiol. 2001;153(5):444-52. 13. dockery dw, pope ca, xu x, et al. an association between air pollution and mortality in six us cities. n engl j med. 1993;329(24):1753-9. 14. srebot v, gianicolo e, rainaldi g, trivella mg, sicari r. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com mohammad shahi et al 114 ozone and cardiovascular injury. cardiovasc ultrasound. 2009;7:30-9. 15. ji m, cohan ds, bell ml. meta-analysis of the association between short-term exposure to ambient ozone and respiratory hospital admissions. environ res lett. 2011;6(2):024006. 16. chay ky, greenstone m. the impact of air pollution on infant mortality: evidence from geographic variation in pollution shocks induced by a recession. q j econ. 2003;118(3):1121-67. 17. akaike h. factor analysis and aic. psychometrika. 1987;52(3):317-32. 18. dominici f, peng rd, bell ml, et al. fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. jama. 2006;295(10):1127-34. 19. chen r, chu c, tan j, et al. ambient air pollution and hospital admission in shanghai, china. j hazard mater. 2010;181(1):234-40. 20. chang c-c, tsai s-s, ho s-c, yang c-y. air pollution and hospital admissions for cardiovascular disease in taipei, taiwan. environ res. 2005;98(1):114-9. 21. sarnat ja, schwartz j, catalano pj, suh hh. gaseous pollutants in particulate matter epidemiology: confounders or surrogates? environ health perspect. 2001;109(10):1053. 22. shrey k, suchit a, deepika d, shruti k, vibha r. air pollutants: the key stages in the pathway towards the development of cardiovascular disorders. environ toxicol pharmacol. 2011;31(1):1-9. 23. lall r, kendall m, ito k, thurston gd. estimation of historical annual pm 2.5 exposures for health effects assessment. atmos environ. 2004;38(31):5217-26. emergency. 2018; 6 (1): e27 le t t e r to ed i to r vagus nerve stimulation and external defibrillation during resuscitation; a letter to editor matthias wittstock1∗, johannes buchmann2, uwe walter1, johannes rosche1,3 1. department of neurology, university medicine rostock, rostock, germany. 2. department of child and adolescence psychiatry and neurology, university medicine rostock, rostock, germany. 3. department of neurology, klinikum kassel, gnh holding ag, kassel, germany. received: march 2018; accepted: april 2018; published online: 26 april 2018 cite this article as: vagus nerve stimulation and external defibrillation during resuscitation; a letter to editor. emergency. 2018; 6(1): 27. dear editor; external defibrillation in patients with implanted neuromodulatory devices is a crucial therapeutic challenge. we report a 63-year-old male patient with refractory epilepsy (re) after recurrent ischaemic strokes in the middle cerebral artery and in the anterior cerebral artery territory 26 and 23 years ago. he received various therapeutic interventions to achieve seizure control with insufficient success. therefore, vagus nerve stimulation (vns) (model pulse 102, aspire sr, cyberonics inc, houston, texas) was applied via insertion of a pulse generator in the left upper chest in 2011. vns stimulation settings were: output current 1.0 ma, pulse width 500 µs, frequency 30 hz, 30s on, 3.0 minute off. a reduction of seizure frequency was achieved. last antiepileptic therapy consisted of levetiracetam 1500 mg td, valproate 1000 mg td, and eslicarbazepine 800 mg td. in 2016, he was admitted because of generalized seizure and aspiration pneumonia. during hospital stay he suffered a cardiac arrest (ca) with pulseless ventricular tachycardia (vt) caused by fulminant pulmonary artery embolism. after successful resuscitation, the patient experienced return of spontaneous circulation (rosc). during resuscitation, biphasic electric shocks were applied using 150 joule and subsequently 360 joule with patches placed approximately 10 cm parasternal and at the left chest below the vns. after successful rosc the vns was checked again and no malfunction could be detected. stimulation settings were not changed. impedance was normal. seizures were not observed during the remaining day. unfortunately, the patient died within one day after successful resuscitation and rosc because of ∗corresponding author: matthias wittstock; department of neurology, university of rostock, gehlsheimer str. 20, 18147 rostock, germany. phone: 0049381-4944742 fax: 0049-381-4944792 e-mail: matthias.wittstock@med.unirostock.de . therapy refractory circulatory insufficiency. vns is an established therapeutic approach in treatment of tre in children and adults to achieve reduction of seizure frequency with proven safety and efficacy (1). the safety of vns in emergency situations like cardiac arrest due to vf with need of external defibrillation and application of large amounts of electrical energy is not clear. external defibrillation in vns patients may potentially be harmful. the literature concerning external defibrillation during resuscitation or external cardioversion (ec) in patients with implanted electronic devices in neurological disorders is sparse (2). in patients with cardiac pacemakers external defibrillation may damage the cardiac device (3). ec applied to deep brain stimulation (dbs) patients may cause thalamotomy or dbs failure (4, 5). application of electroconvulsive therapy in psychiatric disorders seems to be safe. two cases of electroconvulsive therapy (ect) in vns have been reported by sharma et al. (6). the first patient was a 66-year old female with major depression and the second one, a 57-year-old male with a history of bipolar disorder. both had vns for therapy refractory psychiatric illness. ect was applied because of further worsening of the mental state without malfunction of the vns device. to our knowledge, this is the first case of external defibrillation in a patient with vns for tre without alteration of the neurostimulator’s function. external defibrillation applied to vns patients seem to be safe and effective. several steps should be taken to minimize the electrical current flowing through the neurostimulator. first, position the patches as far away as possible from the vns at least 10 cm each. second, position the patches perpendicular to the vns; use the lowest clinically appropriate output setting, and, finally, confirm that the vns is functioning properly after defibrillation (2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. wittstock et al. 2 1. appendix 1.1. acknowledgements none. 1.2. author’s contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. 1.3. conflict of interest the authors declare that there is no conflict. 1.4. funding and support none. references 1. sirven ji, sperling m, naritoku d, et al. vagus nerve stimulation therapy for epilepsy in older adults. neurology. 2000;54(5):1179-1182. 2. venkatraghavan l, chinnapa v, peng p, brull r. noncardiac implantable electrical devices: brief review and implications for anesthesiologists. can j anaesth. 2009;56(4):320-326. 3. allen m. pacemakers and implantable cardioverter defibrillators. anaesthesia. 2006;61(9):883-890. 4. yamamoto t, katayama y, fukaya c, kurihara j, oshima h, kasai m. thalamotomy caused by cardioversion in a patient treated with deep brain stimulation. stereotact funct neurosurg. 2000;74(2):73-82. 5. sobstyl m, michalowska m, fiszer u, zabek m. deep brain stimulation failure due to external cardioversion in a patient with parkinson’s disease. neurol neurochir pol. 2017;51(4):324-330. 6. sharma a, chaturvedi r, sharma a, sorrell jh. electroconvulsive therapy in patients with vagus nerve stimulation. j ect. 2009;25(2):141-143. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2020; 8(1): e54 let ter to editor cross-protection induced by encephalitis vaccines against covid-19 might be a reason for relatively lower mortality rate in some countries shojiro katoh1,2, toshihiko obayashi2, jegatheesan saravana ganesh3, masaru iwasaki4, senthilkumar preethy5, samuel jk abraham4,6∗ 1. edogawa evolutionary lab of science, edogawa hospital campus, 2-24-18, higashi-koiwa, edogawa, tokyo 133-0052, japan. 2. edogawa hospital, 2-24-18, higashi-koiwa, edogawa, tokyo 133-0052, japan. 3. waikato district health board, hamilton 3204, new zealand. 4. yamanashi university-faculty of medicine, 1110, shimokato, chuo, yamanashi 409-3898, japan. 5. the fujio-eiji academic terrain (feat), nichi-in centre for regenerative medicine (ncrm), pb 1262, chennai 600034, tamil nadu, india. 6. the mary-yoshio translational hexagon (myth), nichi-in centre for regenerative medicine (ncrm), pb 1262, chennai 600034, tamil nadu, india. received: april 2020; accepted: april 2020; published online: 21 april 2020 abstract: coronavirus disease 2019 (covid-19) is an on-going pandemic attributed to a novel virus named sars-cov-2. comparing the statistics of incidence and death rates between nations reveals that there is discrepancy amongst countries in these regards, even between countries that share borders. we herein present information from the literature indicating how cross-protection against covid-19 conferred by the encephalitis vaccine could be the reason for lower fatality rate in the countries where immunization against encephalitis is widespread or included in national programs. this may pave the way for arriving at efficient prevention strategies as well as vaccine development. keywords: covid-19; immunity, heterologous; encephalitis; vaccines; japanese encephalitis vaccines cite this article as: katoh s, obayashi t, ganesh js, iwasaki m, preethy s, abraham s. cross-protection induced by encephalitis vaccines against covid-19 might be a reason for relatively lower mortality rate in some countries. arch acad emerg med. 2020; 8(1): e54. covid-19, an acronym for coronavirus disease 2019, previously 2019-ncov, is an on-going pandemic attributed to a novel virus that belongs to the coronavirus (cov ) family, sars-cov-2. as of april 20t h , 2020, the infection has spread to 210 countries with a total of 2,314,621 confirmed cases and 157,847 deaths worldwide, according to the world health organization (who) (https://covid19.who.int/). the covs are a large family of single-stranded rna viruses (+ssrna) that can cross species barriers and cause illnesses in humans ranging from the common cold to more severe diseases such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars) (1). coronaviruses ∗corresponding author: samuel jk abraham; yamanashi university-faculty of medicine, 3-8, wakamatsu, kofu – 400-0866, yamanashi prefecture, japan. tel: +81 (0)55-235-7527, fax: +81 (0)55-235-7569, email: drsam@nichimail.jp; drspp@nichimail.jp were first described in 1966 by tyrell and bynoe who named them based on the crown-like morphology of the spherical virion with surface projections that resemble a solar corona. among the four cov sub-families (alpha-, beta-, gamma-, and delta-coronaviruses), sars-cov-2 belongs to the b lineage of beta-cov and is closely related to the sars-cov. the widely reported initial clinical sign for case detection is pneumonia but gastro-intestinal and asymptomatic infections are also being reported in children (2). with the death toll increasing daily, we considered the mortality rates reported by the european centre for disease prevention and control (3) as of april 20t h , 2020 wherein reported deaths are provided in parentheses after a country’s name: africa: the five countries reporting most deaths are algeria (375), egypt (239), morocco (141), south africa (54) and cameroon (42). asia: the five countries reporting most deaths are iran (5,118), china (4,636), turkey (2,017), indonesia (582) and india (543). america: the five countries rethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. katoh et al. 2 porting most deaths are united states (us) (40,682), brazil (2,462), canada (1,580), mexico (686) and ecuador (474). europe: the five countries reporting most deaths are italy (23,660), spain (20,453), france (19,718), united kingdom (16,060) and belgium (5,683). oceania: the four countries reporting most deaths are australia (70), new zealand (12), guam (5) and northern mariana islands (2). interestingly, countries like the us, spain and italy have more fatalities than china, the epicentre of the outbreak with a much bigger population. in addition to several factors such as the preparedness of countries like south korea and japan due to their earlier fight against sars and mers, the emphasis these countries put on developing in vitro diagnostics and therapeutics against the disease (4), co-operation of the public (5), small but significantly contributing factors such as sense of life worth living (ikigai) in japan (which actually has been proven to decrease the risk of mortality (6)) etc., which potentially decreased fatalities in these countries compared to italy, spain, usa etc., cross-protection against covid-19 conferred by the encephalitis vaccine also seems to be a key parameter worthy of further investigation. this connection is well illustrated by comparing the large number of fatalities in italy with the small number of deaths in their neighbouring country, austria (452 deaths) (3), where, unlike italy, encephalitis vaccination is included in its national immunization schedule (7). this hypothesis is further supported by several additional reports. viral-induced encephalitis is associated with four different kinds of viruses i. arboviruses (e.g., eastern equine encephalitis, japanese encephalitis ( je), la crosse encephalitis, st. louis encephalitis, western equine encephalitis, west nile virus encephalitis), ii. enteroviruses (e.g., coxsackievirus, polioviruses), iii. herpes viruses and iv. other viruses such as measles, mumps, and rubella, which cause secondary encephalitis (8). of these, je is the leading cause of viral encephalitis worldwide, with an estimated 50,000 cases and 15,000 deaths annually. it is a member of the genus flavivirus, which also includes the dengue, yellow fever and west nile viruses and is transmitted by culex mosquitoes. in northern europe and northern asia, flaviviruses causing encephalitis have evolved to use ticks as vectors because of their abundance in cooler climates and hence the encephalitis caused by flavivirus is termed tick-borne encephalitis (9). it is interesting to note that covs, though primarily recognized as respiratory pathogens, are also encephalitis-inducing infectious agents; especially, hcov-229e, hcov-oc43, and sarscov, which possess neuroinvasive properties and their viral rna has been detected in human brains. a few years after the 2002-2003 sars-cov epidemics, associated viral particles were identified in the brain tissue of infected individuals with central nervous system (cns) issues associated with oedema, neurodegeneration, and gliosis. the viruses accessed the brain through the olfactory bulbs, where they infected neuronal cells, and induced a lethal disease in an area of the body with restrained immune infiltration (8). immunization with inactivated je vaccine (inv ) and live attenuated vaccine (lav ) induces a cross-immune response that confers cross-protection against dengue viruses (denvs) (10). tripartite motif-containing (trim) proteins are active players in antiviral innate immunity and overlapping molecular determinants govern the antiviral activities of trim56 against infections by yellow fever virus (yfv ), dengue virus serotype 2 (denv2) and human cov (hcov-oc43) (11). the neuroinvasive properties of sars-cov2 may also underlie respiratory failure in patients with covid-19 (12). furthermore, a case of meningitis was recently attributed to covid-19 in japan (13). next, we considered countries where je immunization is widespread or included in national programs namely, japan, laos, malaysia, nepal, south korea, thailand, sri lanka, and vietnam. again, in all of these countries, the fatality rate due to covid-19 is very low (3) compared with countries that don’t immunize against je. in china, the epicentre of the covid-19 outbreak where the je vaccine is included in its national immunization schedule, the fatality rate is 2.3% compared to 7.3% in italy where the je vaccine is not routinely administered (14). therefore, the implications and applications of the immunological cross-protection conferred by the je vaccine ought to be considered in design and development of vaccines against covid-19 as well as other antiviral therapeutic approaches, so that development of efficient and effective cov vaccine and therapy is ensured. 1. declarations 1.1. acknowledgment the authors wish to acknowledge the staff of edogawa hospital & jbm inc., tokyo, japan for their secretarial assistance and loyola icam college of engineering technology (licet) chennai, india for their support to our research work. 1.2. authors contributions concept, design & definition of intellectual content shojiro katoh concept & reviewtoshihiko obayashi literature search jegatheesan saravana ganesh manuscript preparation senthilkumar preethy manuscript review -masaru iwasaki concept, design, definition of intellectual content, editing and review samuel jk abraham authors orcids shojiro katoh: 0000-0002-8355-9074 toshihiko obayashi: 0000-0001-9774-0133 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e54 jegatheesan saravana ganesh: 0000-0003-1385-3099 masaru iwasaki: 0000-0003-3766-8744 senthilkumar preethy: 0000-0002-9333-0361 samuel jk abraham: 0000-0003-2646-2687 1.3. funding none. 1.4. conflict of interest none. references 1. cascella m, rajnik m, cuomo a, dulebohn sc, di napoli r. features, evaluation and treatment coronavirus (covid-19). statpearls [internet]: statpearls publishing; 2020. 2. velavan tp, meyer cg. the covid-19 epidemic. trop med int health. 2020;25(3):278-80. 3. control ecfdpa. situation update worldwide, as of 20 april 2020 2020 [april 21, 2020]. available from: https://www.ecdc.europa.eu/en/geographicaldistribution-2019-ncov-cases. 4. coronavirus cases have dropped sharply in south korea. what’s the secret to its success? 2020 [april 21, 2020]. available from: https://www.sciencemag.org/news/2020/03/coronaviruscases-have-dropped-sharply-south-korea-whats-secretits-success. 5. what lessons can the us learn from japan and south korea for combating coronavirus? 2020 [april 21, 2020]. available from: https://globalbiodefense.com/2020/03/16/unitedstates-lessons-learned-covid-19-pandemic-responsesouth-korea-japan-observations-hyunjung-kim-gmubiodefense. 6. sone t, nakaya n, ohmori k, shimazu t, higashiguchi m, kakizaki m, et al. sense of life worth living (ikigai) and mortality in japan: ohsaki study. psychosomatic medicine. 2008;70(6):709-15. 7. control ecfdpa. tick-borne encephalitis: recommended vaccinations 2020 [march 26, 2020]. available from: https://vaccineschedule.ecdc.europa.eu/scheduler/bydisease?selected diseaseid=27&selectedcountryidbydisease=-1. 8. talbot pj, desforges m, brison e, jacomy h, tkachev s. coronaviruses as encephalitis-inducing infectious agents. non-flavirus encephalitis in-tech. 2011:185-202. 9. solomon t, dung nm, kneen r, gainsborough m, vaughn dw, khanh vt. japanese encephalitis. journal of neurology, neurosurgery & psychiatry. 2000;68(4):40515. 10. li j, gao n, fan d, chen h, sheng z, fu s, et al. crossprotection induced by japanese encephalitis vaccines against different genotypes of dengue viruses in mice. scientific reports. 2016;6(1):1-9. 11. liu b, li nl, wang j, shi p-y, wang t, miller ma, et al. overlapping and distinct molecular determinants dictating the antiviral activities of trim56 against flaviviruses and coronavirus. journal of virology. 2014;88(23):1382135. 12. li yc, bai wz, hashikawa t. the neuroinvasive potential of sars-cov2 may play a role in the respiratory failure of covid-19 patients. journal of medical virology. 2020. 13. moriguchi t, harii n, goto j, harada d, sugawara h, takamino j, et al. a first case of meningitis/encephalitis associated with sars-coronavirus-2. international journal of infectious diseases. 2020. 14. onder g, rezza g, brusaferro s. case-fatality rate and characteristics of patients dying in relation to covid-19 in italy. jama. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2020; 8(1): e15 rev i ew art i c l e the evolving role of esmolol in management of prehospital refractory ventricular fibrillation; a scoping review dennis miraglia1∗, lourdes a. miguel1, wilfredo alonso1 1. department of internal medicine, good samaritan hospital, aguadilla, pr, united states received: january 2020; accepted: january 2020; published online: 25 february 2020 abstract: introduction: few studies have described their experience using esmolol, an ultra-short acting îš-adrenergic antagonist, in the emergency department (ed) as a feasible adjuvant therapy for the treatment of refractory ventricular fibrillation/pulseless ventricular tachycardia (vf/pvt) out-of-hospital cardiac arrest. however, there is currently insufficient evidence to support the widespread implementation of this therapy. the aim of this scoping review was to summarize the current available evidence on the use of esmolol as an adjuvant therapy for refractory vf/pvt out-of-hospital cardiac arrest, as well as to identify gaps within the literature that may require further research. methods: we conducted a comprehensive literature search of medline via pubmed, embase, scopus, and the cochrane central register of controlled trials (central) on july 5, 2019. the search was restricted to articles that were published from january 2000 to july 2019. google scholar was searched and reference lists of relevant papers were examined to identify additional studies. we included any controlled clinical study design (randomized controlled trials and non-randomized controlled trials) and observational studies (cohort studies and case-control studies) in adults providing information on the use of esmolol as an adjuvant therapy for refractory vf/pvt out-of-hospital cardiac arrest. results: the search yielded 2817 unique records, out of which 2 peer-reviewed articles were found relating to the research purpose totaling 66 patients 33.3% (n = 22) of which received esmolol. these studies found that sustained return of spontaneous circulation (rosc) was significantly more common in the patients that received esmolol compared to the control group. however, no statistically significant outcomes were found regarding survival to discharge and favorable neurological outcome. no randomized controlled trials were identified. conclusion: to date, it is difficult to conclude the real benefit of esmolol as an adjuvant therapy for refractory vf/pvt out-of-hospital cardiac arrest based on the available evidence. the findings of this scoping review suggest that there is a paucity of research and limited evidence to support this therapy. keywords: cardiopulmonary resuscitation; esmolol; out-of-hospital cardiac arrest; ventricular fibrillation cite this article as: miraglia d, a. miguel l, alonso w. the evolving role of esmolol in management of pre-hospital refractory ventricular fibrillation; a scoping review. arch acad emerg mede. 2020; 8(1): e15. 1. introduction in 2016, the annual estimated incidence of emergency medical services (ems)-assessed out-of-hospital cardiac arrest reported by the resuscitation outcomes consortium (roc) epistry for cardiac arrest was about 356,500 people of all ages in the united states (us). among ems-treated outof-hospital cardiac arrest patients, about 21% had shock∗corresponding author: dennis miraglia, department of internal medicine, good samaritan hospital, p.o. box: 4055, aguadilla, pr, united states; e-mail: dennismiraglia@hotmail.com able rhythms of ventricular fibrillation/pulseless ventricular tachycardia (vf/pvt). survival to hospital discharge after ems-treated cardiac arrest was about 11.4%, while this rate was 37.4% for bystander-witnessed vf cardiac arrest in patients of all ages (1, 2). vf is a life-threatening arrhythmia that could lead to sudden cardiac death if not treated emergently. currently, the american heart association (aha) recommends immediate electrical defibrillation as the most effective treatment for vf/pvt (3, 4). however, there is a subgroup of patients in which vf remains refractory to standard electrical defibrillation (5, 6). refractory vf is defined as vf unresponsive to at least three standard defibrillation attempts and advanced cardiovascular life support (acls); this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. miraglia et al. 2 however, currently, neither a clear consensus to the definition of refractory vf nor best-established practices for the management of refractory vf exist (7). since there is no consistent definition for refractory vf in the clinical literature, we used the one cited above throughout this review. few observational studies have described their experience with pre-hospital double defibrillation to treat refractory vf/pvt. these studies have been unable to reach a conventional threshold for statistical or clinical significance, although this does not mean that it is safe to conclude that there is no difference (8-11). there may be better strategies for treating pre-hospital refractory vf/pvt than the use of double defibrillation. incorporation of mechanical chest compressions devices (lucas) and earlier deployment of extracorporeal membrane oxygenation (ecmo) assisted revascularization have shown promising results. therefore, ecmo has been increasingly used as a bridge to definitive treatment including revascularization (cag and pci) in patients with refractory cardiac arrest (12-20). the beta-blocker, esmolol has been recently studied as a feasible adjuvant therapy for patients during both electrical storm (es) and refractory vf/pvt; offering a potential lifesaving treatment option for these patients (2126). however, the limited evidence about the rationale behind the use of intravenous esmolol for the treatment of refractory cardiac arrest makes it a unique and unproven therapy still to be proven. consequently, there seems to be a need to review the literature regarding the use of esmolol for refractory vf/pvt out-of-hospital cardiac arrest in more detail to: identify areas for future research, and to develop strategies for a clinical protocol that will offer a potential lifesaving treatment option for this specific patient population, which is in accordance with the recommendations in the current clinical guidelines. a scoping review was deemed most appropriate because it is exploratory in nature. all methodologies will be considered in the process of this review, as there are few studies evaluating esmolol for refractory vf/pvt outof-hospital cardiac arrest. therefore, the scoping review will identify the feasibility of future work in this area from a variety of methodological perspectives. this paper will summarize the state of the current literature on the use of esmolol in the emergency department (ed) as a feasible adjuvant therapy for refractory vf/pvt out-of-hospital cardiac arrest and identify gaps that will provide direction for future research in the area. 2. methods we followed the prisma-scr (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews) guidelines developed following published guidance from the equator network (enhancing the quality and transparency of health research) (27) and the methodological framework for conducting a scoping review developed by arksey and o’malley (28). a scoping review protocol was not drafted. a scoping review is the process of mapping the main concepts of a research area to its source and evidence available in the literature. the five stages the authors developed were followed in order to maintain a transparent method for data collection, analysis, and interpretation: 1) identifying the research question; 2) identifying relevant studies; 3) selecting studies; 4) charting the data; and 5) collating, summarizing, and reporting the results (28). 2.1. stage 1: identifying the research question the aim of this scoping review was to gain a clear understanding of the current available literature on the use of esmolol in the ed as an adjuvant therapy for patients with refractory vf/pvt out-of-hospital cardiac arrest. a scoping review should be undertaken to determine the value of undertaking a full systematic review and forms part of the complex intervention framework (29, 30). the research objectives of this review were to: 1) summarize the current base of evidence on this intervention for refractory vf/pvt outof-hospital cardiac arrest; 2) identify gaps in the literature that may require further research. the review questions for this scoping review were formulated following the picot method. p (population) people (≥18 years old) who suffer from refractory vf/pvt out-of-hospital cardiac arrest, i (intervention) a pharmacology intervention (esmolol), c (comparator) no esmolol (control), o (outcomes) survival to discharge and favorable neurological outcome and longterm survival and favorable neurological outcome, t (time) all studies from january 2000 to july 2019 were considered. studies were not limited according to the time of follow-up. 2.2. stage 2: identifying relevant studies databases we searched the following databases for eligible articles on july 5, 2019: medline via pubmed, embase, scopus, and the cochrane central register of controlled trials (central), as well as the reference lists of all selected articles. additionally, google scholar was searched for any additional citations. finally, we searched for unpublished or ongoing clinical trials using the who international clinical trials registry (who ictrp), and the clinicaltrials.gov registry on july 12, 2019. the search was repeated one month prior to submission for publication to ascertain that no new literature was published in the interim. we believed these four search databases would reach all the relevant journals within the area of interest. overall, 2817 articles were found using the search terms and databases. search terms the search strategy was developed by two investigators (dm and lm), with the help of healthcare librarians. we this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e15 used the press (peer review of electronic search strategies) checklist to develop the research strategy (31). the search strategy was developed according to keywords related to esmolol in combination with "out-of-hospital cardiac arrest" and "refractory ventricular fibrillation". keywords used in the search were based on the implemented pico model, which was first defined for use in medline via pubmed and subsequently adapted for the other databases. the example of pubmed research query was: ((("cardiopulmonary resuscitation" [title/abstract] or "cpr" [title/abstract] or "management" [title/abstract] or "treatment" [title/abstract] or "pre-hospital cardiac arrest"[title/abstract] or "out-of-hospital cardiac arrest" [title/abstract] or "emergency department" [title/abstract] or "ed" [title/abstract])) and (("sudden" [title/abstract] and "death") [title/abstract] or "refractory ventricular tachycardia" [title/abstract] or "refractory ventricular fibrillation"[title/abstract] or "rvt" [title/abstract] or "rvf" [title/abstract] or "pulseless ventricular tachycardia" [title/abstract] or "pvt" [title/abstract] or "ventricular fibrillation" [title/abstract] or "ventricular arrhythmia" [title/abstract] or "heart arrest" [title/abstract] or "cardiac arrest" [title/abstract])) and "esmolol" [title/abstract] or "beta-blockade"[title/abstract]. 2.3. stage 3: study selection inclusion and exclusion criteria we used the pcc (population, concept, and context) framework to delineate eligibility criteria (32). studies were eligible for inclusion if they reported on the use of esmolol as an adjuvant therapy for patients (≥18 years old) undergoing resuscitation for refractory vf/pvt out-of-hospital cardiac arrest and included any controlled clinical study design (randomized controlled trials and non-randomized controlled trials) and observational studies (cohort studies and case-control studies) with a control group (i.e. patients not receiving esmolol) and were published between january 2000 and july 2019. this time period was selected because a preliminary review suggested there would not be any relevant articles prior to the year 2000. studies were excluded if they were not written in english, included in-hospital cardiac arrest, reported on animal studies, reported on traumatic cardiac arrest, reported on pediatric cardiac arrest, reported cardiac arrests in pregnancy, and patients had received esmolol for arrhythmias other than vf/pvt. the databases were searched by one author (dm). following the search and the automatic removal of duplicates, the titles and abstracts were subsequently appraised for eligibility by two independent authors (dm and lm). the full texts of titles and abstracts were reviewed for studies that were considered potentially relevant. any discrepancies regarding the selection of articles retained for full-text review were resolved by discussion with a third figure 1: preferred reporting items for systematic reviews and meta-analyses flowchart. reviewer (wa). the selection process is described in figure 1. 2.4. stage 4: charting the data the charting of data is a descriptive-analytical method that is used to extract the information from individual articles (28). excel 2019 (microsoft, redmond, wa) was utilized for this stage. we collected descriptive characteristics such as first author, year of publication, study period, the country where the study was held, study design, research setting, study population, sample size, measures, interventions, key findings, and limitations. data for all reported outcomes were extracted from every study included in the review by two independent reviewers (dm and lm). discrepancies regarding the extracted data were resolved by discussion with a third reviewer (wa). descriptive statistics were summarized by presenting the median (iqr) for continuous variables and number and percentage for categorical variables. table 1 provides an overview of the articles selected for inclusion. 2.5. stage 5: collating, summarizing, and reporting the results a total of 7 studies were identified as relevant to the review. two studies were noted to be directly related to the use of esmolol as an adjuvant therapy for refractory vf/pvt outof-hospital cardiac arrest. the remaining 5 studies were applicable to in-hospital cardiac arrest. these studies were excluded at this level because different types of beta-blockers other than esmolol were used as adjuvant therapy. the discarded articles were approved by the authors before the qualthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. miraglia et al. 4 table 1: details of characteristics and outcomes of studies included in the scoping review author, year, country design, setting, and participants intervention key results driver et al. 2014 united states of america (24) a retrospective investigation from january 2011 to january 2014 in an urban academic ed. this study included 25 patients (≥18 years old) with out-ofhospital or ed cardiac arrest with refractory vf/pvt who were resistant to at least ≥3 defibrillations, 3 mg of epinephrine, and 300 mg of amiodarone. six patients received esmolol (intervention) in the ed during ca and were compared to those who did not (control). patients received esmolol 500 mcg/kg bolus followed by a 0–100 mcg/kg/min maintenance infusion. key outcomes of patients who received esmolol (n = 6) compared with those who did not (n = 19). the esmolol group exhibited better rates of temporary rosc and survival to icu admission. when comparing survival rates and survival with favorable neurological outcome, the patients that received esmolol had better outcomes than those who did not. however, no statistically significant outcomes were found in survival to discharge and favorable neurological outcome. overall, 4 (66.7%) in the esmolol group vs. 6 (31.6%) in the control group had sustained rosc and survived to icu admission, respectively. three (50%) vs. 3 (15.8%) survived to hospital discharge and 3 (50%) vs. 2 (10.5%) survived to discharge with a cpc ≤ 2. lee et al. 2016 south korea (25) a retrospective single-center prepost study that evaluated records from january 2012 to december 2015. this study included 41 patients (≥18 years old) with refractory vf out-of-hospital cardia arrest who were resistant to ≥3 defibrillations, 3 mg of epinephrine, 300 mg of amiodarone, and had no rosc after >10 min of cpr). sixteen patients received esmolol (intervention) at the ed during ca and were compared to those who did not (control). patients received esmolol 500 mcg/kg bolus followed by a 0–100 mcg/kg/min maintenance infusion. key outcomes of patients who received esmolol (n = 16) compared with those who did not (n = 25). sustained rosc was significantly more common in the esmolol group, compared to the control group (p = 0.007). the esmolol group also exhibited better rates of temporary rosc and survival to icu admission. however, there were no significant differences in the rates of survival to discharge and favorable neurological outcome (p = 0.36). overall, 9 (56.3%) in the esmolol group vs. 4 (16%) in the control group had sustained rosc and survived to icu admission, respectively. three (18.8%) vs. 2 (8%) survived to discharge and had a cpc ≤ 2 at 30, 90, and 180 days. ca = cardiac arrest; cpc = cerebral performance category; ed = emergency department; icu = intensive care unit; pvt = pulseless ventricular tachycardia; rosc = return of spontaneous circulation; vf = ventricular fibrillation; cpr = cardiopulmonary resuscitation. notes: neurological outcomes were evaluated using the glasgow-pittsburgh cerebral performance category (cpc) scale. favorable neurological outcomes were defined as a cpc score of 1–2. itative analysis was completed. finally, a total of 2 observational studies were included. tables 2–4 summarize details of the studies according to demographics, presentation, resuscitative parameters, and outcomes. 2.6. ongoing consultation it is suggested that a scoping review should include the consultation of experts in the area of research (28). consultation was not included in this study due to this approach being relatively new and esmolol being used off-label with no information available from randomized controlled trials. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e15 table 2: esmolol in out-of-hospital cardiac arrest patients with refractory vf/pvt author, year, country study design patients, n received esmolol, n age,median (iqr), yr male, n(%) witnessed arrest n (%) bystander cpr, n (%) initial rhythm vf, n (%) defibrillation attempts, median (iqr) driver et al. ro 25 6 54.5 (47–59) 6 (100) 5 (83.3) 3/4a b 5 (83.3 ) 6.5c (5–9.5) 2014 usa(24) lee et al. ro 41 16 58 (45.8–72) 14 (87.5) 14 (87.5) 11(68.8) 14 (87.5) 6 (6–8.75) 2016 sk(25) cpr = cardiopulmonary resuscitation; ro = retrospective observational; vf = ventricular fibrillation; vt = ventricular tachycardia; usa = united states of america; sk = south korea. notes: total percentages refer to studies with available data. all continuous variables are reported as median interquartile range (iqr) unless specified otherwise a refers to the patient who arrested in the ed; one patient was awake on ems arrival, then arrested. b refers to mechanical cpr with lucas device. c refers to implantable cardioverter-defibrillator (icd) firings (approximately every 2-3 min) until it failed 30 min after ed arrival; does not include icd firings for one patient. 3. results 3.1. study populations and settings the initial electronic database search yielded 2817 records. we first removed 1274 duplicates and then eliminated 1536 papers following inspection of the titles and abstracts. we read the full text of each of the 7 remaining articles. following the inclusion criteria outlined above, 2 retrospective observational studies were found relating to the research purpose totaling 66 patients, 33.3% (n = 22) of which received esmolol (24, 25). no randomized or non-randomized controlled trials on esmolol for refractory vf/pvt out-of-hospital cardiac arrest were identified or ongoing at the time of the search. all studies were published between 2014 and 2016, while patient enrollment periods extended to as early as 2011. both studies were conducted in a single center with percutaneous coronary intervention capability, but at different institutions. one study was performed in the us (24) and 1 in south korea (25). regarding demographics, all articles identified patients as having pre-hospital or ed refractory vf/pvt at some point during the cardiac arrest. the sample sizes of the patients that received esmolol ranged from 6 to 16, the median age of the patients ranged from 54 to 58 years, and the percentage of males ranged from 87.5% to 100%. most cardiac arrests were witnessed by a bystander, who initiated cardiopulmonary resuscitation (cpr) and were attended by ems providers. 3.2. focus and outcomes there was no substantial heterogeneity of outcome measurement across studies. the definition of refractory vf and a clear protocol was uniform across studies. all studies compared the use of esmolol (intervention) with no esmolol (control) in adult patients with refractory vf/pvt outof-hospital cardiac arrest. both studies enrolled patients with pre-hospital cardiac arrest and diagnosis of vf/pvt who did not respond to at least 3 deïňąbrillation attempts, 3 mg of epinephrine, 300 mg of amiodarone and remained in arrest upon ed arrival. all patients in the esmolol group received a loading dose of 500 mcg/kg esmolol, followed by a continuous infusion of 0–100 mcg/kg/min (24, 25). all studies reported on sustained return of spontaneous circulation (rosc >20 min of spontaneous circulation without recurrence of cardiac arrest) (33), total ed cpr time, total cpr time, survival to intensive care unit (icu) admission, survival to discharge and favorable neurological outcome. one study reported data about the predominance of acute coronary syndrome and emergency coronary revascularization (24). one study reported on survival and favorable neurological outcomes 30 days, 3 months, and 6 months later (25). overall, both studies found that sustained rosc was significantly more common in patients that received esmolol compared to the control group. however, no statistically significant outcomes were found regarding survival to discharge and favorable neurological outcome. neurological outcomes were evaluated using the glasgow-pittsburgh cerebral performance category (cpc) scale. good neurological outcomes were defined as a cpc score of 1–2 (34, 35). the first study was published in 2014 by driver et al. overall, in this study 5 (83.8%) of the patients in the esmolol group had witnessed arrest and 5 (83.8%) had vf as the first documented heart rhythm before receiving esmolol. furthermore, vf was successfully terminated into sustained rosc in 4 (66.7%) patients. in addition, 83.8% received emergent cardiac catheterization and 60% of them were diagnosed as having a st segment elevation myocardial infarction (stemi). ultimately, 3 (50%) of the patients included in this study had a cpc score equal to 1 or 2 on discharge. the authors reported that sustained rosc was significantly more comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. miraglia et al. 6 mon in the esmolol group compared to the control group (66.7% vs. 31.6%). however, there were no significant differences in survival rates (50% vs. 15.8%), and good neurological outcomes between the two groups (50% vs. 10.5%). all patients in this study received conventional cpr by first responders and most had automated cpr with a lucas device (physio-control) and an impedance threshold device (itd) (resqpodtm) when they were transported to the ed (24). the second study was published in 2016 by lee et al. overall, in this study 14 (87.5%) of the patients in the esmolol group had witnessed arrest and 11 (68.8%) had vf as the first documented heart rhythm before receiving esmolol. furthermore, vf was successfully terminated into sustained rosc in 9 (56.3%) patients. in addition, 93.8% of the arrests had cardiac origin, but the study did not report if any of the patients suffered from acute coronary syndrome or received emergent reperfusion therapy. ultimately, 3 (18.8%) of the patients included in this study had a cpc score equal to 1 or 2 on discharge, and 30 days, 3 months and 6 months later. this study found similar results to the study described above. the authors reported that sustained rosc was significantly more common in the esmolol group compared to the control group (56.3% vs. 16.0%, p = 0.007). however, there were no significant differences in survival rates and good neurological outcomes 30 days, 3 months and 6 months later (18.8% vs. 8%, p = 0.36) (25). 4. discussion this scoping review sought to describe the available evidence and identify the gaps in the literature on the use of esmolol as a feasible adjuvant therapy for the treatment of refractory vf/pvt out-of-hospital cardiac arrest. our scoping review revealed that only 2 studies have evaluated the use of esmolol as an adjuvant treatment for adult patients with refractory vf/pvt out-of-hospital cardiac arrest. both of these studies showed that sustained rosc was significantly more common in the esmolol group, compared to the control group. survival to discharge and favorable neurological outcome were at least 2-fold better in the esmolol group, compared to the control group, although these increases were not statistically significant. one study did not report data regarding 30-day, 6-month and long-term survival and favorable neurological outcome (24). the findings of these studies suggest that esmolol may considerably improve the probability of successful rosc, but not survival, as approximately 2/3 of the patients that had sustained rosc did not survive to discharge. a major limitation discovered in this review is the paucity of research and lack of literature to support this therapy. we identified these as the main important gaps in the available literature. furthermore, our review revealed that all studies were observational in nature and conducted on a small number of patients. in addition, we did not identify any studies assessing the cost-effectiveness of esmolol for pre-hospital refractory vf. we did not identify any registered or ongoing clinical trials on esmolol for refractory vf out-of-hospital cardiac arrest on the international clinical trials registry platform. despite these limitations, the findings from this review highlight an area of research that may contribute to improving survival of people with refractory vf/pvt out-of-hospital cardiac arrest, but would need to be investigated in a more robust manner. epinephrine has been a longstanding treatment for cardiac arrest patients; yet, the literature has not shown an increase in survival rates when it has been used in higher doses (36). during prolonged resuscitation from cardiac arrest there is an increase in sympathetic tone, at least partially, due to the mechanism of epinephrine. the activation of β-adrenoreceptors by epinephrine causes up to 4-fold increase in myocardial oxygen consumption in patients with vf/pvt via its positive chronotropic and inotropic effects (37, 38). in addition, coronary blood flow may be reduced to up to 40%, increasing myocardial ischemia (37). esmolol has shown promising results to support the effectiveness of beta-1 selective blockade in refractory vf/pvt (21, 23-26). esmolol as an adjuvant therapy may be an alternative treatment for these patients since it is an ultra-short acting beta-1 selective adrenergic receptor blocker and a perfect sympatholytic agent, which is extremely cardioselective and has a quick onset of action. it has the fastest onset (90 seconds) and the shortest half-life ([t1/2] = 9 minutes) among beta-blockers (39). esmolol is also able to mitigate the depression of vf threshold produced by high doses of epinephrine used during cardiac arrest, due to its ability to dampen the sympathetic tone, which is one of the proposed mechanisms behind the use of esmolol for refractory vf. due to its quick onset and offset, it is ideal for these patients, without having the excessive/prolonged effects of the drug during and after resuscitation (37-40). when esmolol is administered as a bolus, it is followed by a continuous infusion, the onset of activity occurs within 2 minutes, with 90% of b-blockade at 5 minutes (39). generally, for cardiac arrest patients, a loading dose of 500 mcg/kg over one minute has been administered prior to a maintenance infusion dose of 0–100 mg/kg/min (24, 25). esmolol, as an adjuvant therapy for refractory vf/pvt, could be easily used in the ed and in-patient hospital settings. however, esmolol is not readily available for pre-hospital use, and, as a result, patients who experience refractory out-of-hospital cardiac arrest are reliant on rapid transportation to the closest hospitals prepared to handle these types of patients. hence, despite the current advances in pre-hospital care and the feasibility to provide quick access to perfusion/reperfusion therapies, the main goal of pre-hospital care for patients with refractory cardiac arrest is rapid transport to definitive care this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e15 table 3: esmolol in the out-of-hospital cardiac arrest patients with refractory vf/pvt author, year, country adrenaline, (mg), median (iqr) amiodaron, (mg), median (iqr) esmolol loading dose (mcg/kg) esmolol drip, (mcg/kg/min) total cpr time (min), median (iqr) temporary rosc a , n(%) sustained rosc b , n(%) survival to icu admission, n(%) driver et al. 2014 usa (24) 6 (5–7.75) 375 (300–450) 500 0–100 63 (57–83) 4 (66.7) 4 (66.7) 4 (66.7) lee et al. 2016 sk (25) 6 (3.3–9) 450 (300–450) 500 0–100 55 (35.3–70.3) 13 (81.3) 9 (56.3) 9 (56.3) cpr = cardiopulmonary resuscitation; icu = intensive care unit; rosc = return of spontaneous circulation; vf = ventricular fibrillation; vt = ventricular tachycardia; usa = united states of america; sk = south korea. notes: total percentages refer to studies with available data. all continuous variables are reported as median interquartile range (iqr) unless specified otherwise. a refers to non-fleeting spontaneous circulation lasting >30 seconds but <20 minutes. b refers to 20 min of spontaneous circulation without cardiac arrest. table 4: esmolol in the out-of-hospital cardiac arrest patients with refractory vf/pvt author, year, country survival to discharge, n(%) 30-day survival, n(%) 3 and 6 months survival, n(%) cpc≤2 at discharge , n(%) cpc≤2 at 30 days, n (%) cpc≤2 at 3 and 6 months, n (%) driver et al. 2014 usa (24) 3 (50) . . . . . . 3 (50) . . . . . . lee et al. 2016 sk (25) 3 (18.8) 3 (18.8) 3 (18.8) 3 (18.8) 3 (18.8) 3 (18.8) cpc = cerebral performance category; ellipses (...) = data not available; vf = ventricular fibrillation; vt = ventricular tachycardia; usa = united states of america; sk = south korea. notes: total percentages refer to studies with available data. while supporting patients (18-20, 41). the results of these studies are not to be generalized as these studies were performed at a single medical center and had a small sample size; however, these studies showed a signal of benefit and a feasible adjuvant treatment strategy for one of the most difficult challenges of resuscitative medicine. 5. limitations this study had some limitations. first, the primary limitation of the scoping review methodology is the lack of quality assessment of the included articles. however, the goal of a scoping review is simply to identify research that has been conducted, not necessarily to assess quality (28). while the quality assessment was not a goal of the research, quality should be considered before applying these findings in clinical practice. second, the scientific evidence we used has limitations due to small sample size and the nature of single-centered, retrospective, non-randomized, observational studies with their subjective potential for selection bias. third, the studies did not report collapse time to esmolol bolus or maintenance infusion; in addition, there was a lack of follow-up in one study and as a consequence, no long-term survival or functional outcomes were reported. fourth, all of the studies included in this review listed at least two or three limitations in the discussion section of the article, and there is a risk of bias if the authors of the included articles did not mention all the true limitations of their studies. fifth, there might be considerable differences between ems and variations in the transport of patients. finally, the rationale for undertaking an early scoping review is now recognized in that such review has, among other things, the potential to influence the design of future primary studies and systematic reviews. furthermore, we plan to conduct a systematic review, which will allow us to incorporate studies that have been published after the cut-off date of our searches and thereby, ensure an up to date review on this important topic. 6. conclusion current research shows promising results on the use of esmolol as feasible adjuvant therapy for refractory vf/pvt outof-hospital cardiac arrest. however, there is a paucity of research and a lack of literature to support this therapy. we urgently need studies on esmolol, to identify differences in important clinical outcomes such as survival to discharge and favorable neurological outcome. as studies become available on this topic, they will help us justify its use and application in clinical practice. it is recommended to evaluate these outcomes in randomized controlled trials in order to obtain a higher level of scientific evidence. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. miraglia et al. 8 7. appendix 7.1. perspective as mentioned above, we plan to conduct a systematic review and meta-analysis in a second research to evaluate the efficacy of esmolol in patients with refractory vf/pvt out-ofhospital cardiac arrest. 7.2. acknowledgements the authors would like to thank the library staff from the veterans affairs caribbean healthcare system library service for assistance with producing the search strategy. 7.3. authors contributions dm, lm and wa were responsible for the project design. dm and lm were responsible for the initial database search, data abstraction, and drafted the original manuscript. all authors reviewed, proofread, and approved the final version of the manuscript. dm takes responsibility for the paper as a whole. authors orcids dennis miraglia: 0000-0002-3887-3320 7.4. funding support the author(s) received no financial support for the research, authorship, and/or publication of this article. 7.5. conflict of interest the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this 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external compressions during experimental cardiopulmonary resuscitation. resuscitation. 2005;65(3):357-63. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion appendix references emergency. 2018; 6 (1): e35 or i g i n a l re s e a rc h performance of local anesthesia with lidocaine among opium addicts and non-addicts; a case control study alireza majidi1, tala shahhosseini2∗, sadrolla mahmoudi3 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye pakdasht hospital, shahid beheshti university of medical sciences, tehran, iran. 3. emergency department, baqiyatallah hospital, baqiyatallah university of medical sciences, tehran, iran. received: may 2018; accepted: june 2018; published online: 5 june 2018 abstract: introduction:compared to ordinary people, addicts usually have a lower pain threshold. the current work attempts to compare the performance of local analgesia with lidocaine among opium addicts and non-addicts. methods:in this case-control study, opium addicts and healthy patients with skin laceration referring to emergency departments of two educational hospitals were compared regarding the response to local anesthesia with lidocaine, as well as side effects. results: 197 cases with the mean age of 43.44 ± 20.12 years were studied (72.1% male). 98 (49.8%) cases were addicts and 99 (50.2%) were healthy people. two groups were similar regarding age (p = 0.281), sex (p = 0.666), and wound size (p = 0.272). the amount of pain reduction 5 (df =1.5, f=0.38, p = 0.88) and 10 (df =1.5, f=0.58, p = 0.72) minutes after lidocaine injection was not different between the groups. subgroup analysis based on sex and age of patient did not show any differences between the groups (p > 0.1 for all analysis). the mean duration of analgesia was 16.4 ± 5.37 minutes in addicts and 16.95±1.79 in control group (p = 0.334). conclusion: lidocaine, as a commonly used local anesthetic agents, does not show different effects in addicts and non-addicts in repairing skin laceration. keywords: lidocaine; opium dependence; anesthetics, local; case-control studies; pain management © copyright (2018) shahid beheshti university of medical sciences cite this article as: majidi a, shahhosseini t, mahmoudi s. performance of local anesthesia with lidocaine among opium addicts and nonaddicts; a case control study. emergency. 2018; 6(1): e35. 1. introduction f or decades, a new field of worry has been raised in surgery, which is about people who have drug dependence, especially in cases of intravenous drug use (1, 2). acute pain would be partially relieved or not relieved at all among drug users (3). compared to ordinary people, addicts usually have a lower pain threshold. opium addicts have changes in function, sensitivity, reduction, and/or decreased number of opioid receptors systematically (4). this is why addicts are more resistant to analgesia and narcotics used (5-7). studies have shown the fact that addicted people experience shorter anesthesia or sedation duration and depth when compared to non-addicts (7, 8). this fact has encouraged researchers to try to provide routes to use supplemen∗corresponding author: tala shahhosseini; emergency department, shohadaye pakdasht hospital, pakdasht, tehran, iran. email: talashahhosseini@gmail.com tel: 00989122361012 tary drugs in order to alleviate patients’ pain throughout the procedures (4).the prevalence of addiction to narcotics was 2.26% in 2011, according to reports by the united nations office on drugs and crime (unodc). furthermore, iran is in the second place of narcotic consumption, worldwide (available on: http://www.unodc.org). the current work attempts to compare the performance of local analgesia with lidocaine among opium addicts and non-addicts regarding the rate of pain reduction and side effects. 2. methods 2.1. study design and setting in this case-control study, patients with skin laceration who were referred to emergency departments of two hospitals affiliated to shahid beheshti university of medical sciences (imam hossein and shohadaye tajrish hospitals) were enrolled. addicted patients were compared with non-addicts in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. majidi et al. 2 table 1: baseline characteristics of studied patients variables case (n=98) control (n= 99) p sex male 72 (73.5%) 70 (70.7%) 0.666 female 26 (26.5%) 29 (29.3%) age mean ± sd 44.95±20.52 41.84±19.87 0.281 wound size mean ± sd 5.81±0.90 5.86±1.01 0.272 systolic blood pressure (mmhg) baseline 125.30±11.51 118.87±13.70 <0.001 30 min 122.86±9.82 118.74±8.20 <0.001 diastolic blood pressure (mmhg) baseline 80.46±5.52 87.08±72.40 0.863 30 minute 79.66±2.83 79.85±1.12 0.420 pulse rate baseline 81.45±8.49 79.70±5.40 0.321 30 minute 81.53±9.44 79.71±5.95 0.344 o2 saturation baseline 95.94±1.69 96.94±1.02 <0.001 30 minute 95.04±9.73 103.11±60.41 <0.001 pain score baseline 6.1±1.4 5.4±1.0 <0.001 5 minute 4.04±1.76 3.00±1.26 <0.001 10 minute 2.00±2.12 1.43±0.72 0.034 duration of anesthesia mean ± sd 16.40±5.38 16.96±1.80 0.003 median (iqr) 16 (14-18) 17 (16-18) sd: standard deviation, iqr: inter-quartile range. terms of response to anesthesia with local lidocaine, as well as side effects. the participants gave their informed consents verbally and all the cases and included data were kept by the principal investigator to maintain patients’ privacy. people were free to decide to stay in the study or leave in any step with no penalty. 2.2. participants patients 15 years of age or older with laceration size of more than 5cm, were divided into two groups of addicts and nonaddicts. people with any sensory or mental disorder who have limitations to reliably express their pain severity as well as cases with tendon injury or positive history of allergic reaction to lidocaine or cardiac problems were excluded. participants were defined as addict when they had used opioids daily for the last 6 months, and had shown withdrawal symptoms. 2.3. data gathering a checklist consisting of demographic data (age, sex), vital signs (blood pressure, respiratory rate, o2 saturation) before and 30 minutes after local anesthesia, pain score at 0, 5, and 10 minutes after local anesthesia, as well as duration of anesthesia was filled for all case (addicts) and control (healthy) group members by a senior emergency medicine resident. 2.4. procedure wounds underwent complete sterilization using sterile medical equipment and detergents. local anesthesia was applied by injecting subcutaneous lidocaine 2% solution (maximum dose of 5 mg/kg) at the laceration site after asking the participants about their relevant medical background like any allergy to the medication or any cardiologic problems. using numeric rating scale (nrs), the pain severity of patients was recorded before and 5 and 10 minutes after injection of local lidocaine (the maximum dose of 5 mg/kg). nrs ranges between 0 and 10, where the former shows no pain, while a score of 10 shows the highest level of pain, which was not experienced by the patients. 2.5. statistical analysis the data were entered to spss11 for windows, while quantitative variables were shown by mean ± standard deviation and qualitative ones were reported using frequency. independent t-test was used to compare quantitative data, while chi-square test was used for qualitative ones. since systolic blood pressure (sbp), arterial o2 saturation and pain score differed between the groups before lidocaine administration; this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e35 figure 1: comparing the trend of pain reduction 5 (p = 0.88) and 10 (p = 0.72) minutes after lidocaine injection between case and control groups. analysis of covariance was used to compare the findings after intervention. effects of age and sex on lidocaine efficacy were investigated via two-way anova. p value <0.05 was considered as significance level. 3. results 3.1. baseline characteristics 197 cases with the mean age of 43.44 ± 20.12 (16-90) years were studied (72.1% male). 98 (49.8%) cases were addicts (case group) and 99 (50.2%) were healthy people (control group). table 1 compares the baseline characteristics of studied groups. the two groups were similar regarding age (p = 0.281), sex (p = 0.666), and wound size (p = 0.272). pain score at the time of admission was 6.1 ± 1.4 in addicts and 5.4 ± 1.0 in control group (p<0.001, clinically not important). 3.2. pain management figure 1 compares the trend of pain reduction between the groups, 5 and 10 minutes after lidocaine injection. the rate of pain reduction 5 (df =1.5, f=0.38, p = 0.88) and 10 (df =1.5, f=0.58, p = 0.72) minutes after lidocaine injection was not different between groups. subgroup analysis based on sex and age of patients did not show any differences between the groups regarding the trend of pain reduction after 5 and 10 minutes (p > 0.1 for all analyses). the mean duration of analgesia was 16.4 ± 5.37 minutes in addicts and 16.95±1.79 minutes in control group (p = 0.334). although differences of vital signs between groups 30 minutes after lidocaine injection were statistically significant, they were clinically important (table 1). 4. discussion the current study disclosed no difference in pain reduction rate among addict and non-addict participants after using lidocaine as an anesthetic agent for skin laceration. the duration of action was similar in case and control groups. through a study in iran, which was done between 2010 and 2011, investigators found that in people with fractured lower limb, duration of anesthesia was shorter among opium addicts compared to non-addicts when spinal anesthesia was tried (4). they also believed that use of multiple medications or higher doses of anesthetics was required in drug users, mainly because of their absolute tolerance to the medication. narcotics can influence numerous receptors in central and peripheral parts of nervous system (6, 9). these receptors would interrupt local anesthesia due to being interfered by opioids (10, 11). the current study tried to match age and sex between case and control groups. however, previous studies have pointed out that age and body characteristics like weight and height usually have no impact on anesthesia onset and duration (4). regarding the changes in vital signs and o2 saturation, there was not any clinically significant difference between the groups. most adverse side effects of anesthetic medications are known to manifest in heart and nervous system. the first report of tonic effects of long-acting local anesthetics on heart and brain was provided by albright (12). in terms of cardiac adverse effects, plasma concentration of lidocaine with less than 5mg/ml dose has no toxicity on human heart. in higher serum levels, hypotension would be a cause of worry. cardiac toxicity mainly results from cardiac sodium channel blockage and calcium and potassium ion channels are also affected, particularly in high doses of lidocaine and other similar drugs (13). bradycardia in addition to hypotension, would lead the patient to hypoxia and hypercarbia, resulting in acidosis. acidosis, in turn, could result in more toxicity by decreasing plasma protein binding of lidocaine (14, 15). these were the main events checked in the current study. maximum dose for local injection of lidocaine to be safe is 500-600 mg, which is equal to 7-8 mg/kg. in this study, we used 5mg/kg of the drug for both cases and controls to prevent any serious or permanent side effects. this study evaluated the consequences of lidocaine administration, and it seems useful to carry out future researches, with a bigger sample size from different races, to achieve reliable findings in this regard. 5. conclusion it could be concluded that lidocaine, as a commonly used local anesthetic agent, does not show different effects in addicts and non-addicts in repairing the skin laceration. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. majidi et al. 4 6. appendix 6.1. acknowledgements none. 6.2. author contribution all authors pass the four criteria for authorship contribution based on the international committee of medical journal editors (icmje) recommendations. 6.3. funding/support none. 6.4. conflict of interest none. references 1. karbasy sh, derakhshan p. effects of opium addiction on level of sensory block in spinal anesthesia with bupivacaine for lower abdomen and limb surgery: a case-control study. anesthesiology and pain medicine. 2014;4(5). 2. zirak n, soltani g, javdani n, shamloo as, bameshki a, peyvandi a. effect of fentanyl in spinal anesthesia with bupivacaine in opium abusers. razavi international journal of medicine. 2014;2(1). 3. vosoughian m, dabbagh a, rajaei s, maftuh h. the duration of spinal anesthesia with 5% lidocaine in chronic opium abusers compared with nonabusers. anesthesia & analgesia. 2007;105(2):531-3. 4. mansourian a, askarzadeh m, shabani m, divsalar k. comparison of duration of spinal anesthesia with lidocaine or lidocaine plus epinephrine between addicts and non-addicts. addiction & health. 2012;4(3-4):95-101. 5. bovill j. mechanisms of actions of opioids and nonsteroidal anti-inflammatory drugs. european journal of anaesthesiology (eja). 1997;14:9-15. 6. christie m. cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction. british journal of pharmacology. 2008;154(2):384-96. 7. wu h-e, thompson j, sun h-s, leitermann rj, fujimoto jm, tseng lf. nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord. journal of pharmacology and experimental therapeutics. 2004;310(1):240-6. 8. szeto hh, soong y, wu d, qian x, zhao g-m. endogenous opioid peptides contribute to antinociceptive potency of intrathecal [dmt1] dalda. journal of pharmacology and experimental therapeutics. 2003;305(2):696702. 9. kokki h. spinal blocks. pediatric anesthesia. 2012;22(1):56-64. 10. marchand f, ardid d, chapuy e, alloui a, jourdan d, eschalier a. evidence for an involvement of supraspinal deltaand spinal mu-opioid receptors in the antihyperalgesic effect of chronically administered clomipramine in mononeuropathic rats. the journal of pharmacology and experimental therapeutics. 2003;307(1):268-74. 11. hurley rw, banfor p, hammond dl. spinal pharmacology of antinociception produced by microinjection of mu or delta opioid receptor agonists in the ventromedial medulla of the rat. neuroscience. 2003;118(3):789-96. 12. cox b, durieux me, marcus ma. toxicity of local anaesthetics. best practice & research clinical anaesthesiology. 2003;17(1):111-36. 13. butterworth j, james rl, grimes j. structure-affinity relationships and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor. anesthesia and analgesia. 1997;85(2):336-42. 14. horlocker tt. clinical pharmacology of local anesthetics. anesthesia & analgesia. 2000;90(6):1464-5. 15. burney r, difazio c, foster j. effects of ph on protein binding of lidocaine. anesthesia and analgesia. 1978;57(4):478-80. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e41 or i g i n a l re s e a rc h relationship between thrombosis risk factors, clinical symptoms, and laboratory findings with pulmonary embolism diagnosis; a cross-sectional study rama bozorgmehr1, mehdi pishgahi2∗, pegah mohaghegh3, marziye bayat1, parastou khodadadi1, ahmadreza ghafori1 1. internal medicine department, clinical research development unit, shohadaye tajrish hospital, shahid beheshti university of medical science, tehran, iran. 2. cardiology department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. department of community and preventive medicine, school of medicine, arak university of medical science, arak, iran. received: may 2019; accepted: june 2019; published online: 23 july 2019 abstract: introduction: pulmonary embolism (pe) is a potentially life threatening disease, accurate and timely diagnosis of which is still a challenge that physicians face. this study was designed with the aim of evaluating the relationship between thrombosis risk factors, clinical symptoms, and laboratory findings with the presence or absence of pe. methods: the present retrospective cross-sectional study was performed on patients with suspected pulmonary embolism who were hospitalized in different departments of shohadaye tajrish hospital, tehran, iran, during 1 year. all patients underwent computed tomography pulmonary angiography (ctpa) and then thrombosis risk factors, clinical symptoms, and laboratory findings of confirmed pe cases with ctpa were compared with others. results: 188 patients with the mean age of 61.91 ± 18.25 (20 – 101) years were studied (54.8% male). based on wells’ score, 32 (17.2%) patients were in the low risk group, 145 (78.0%) were in the moderate risk group, and 9 (4.8%) patients were classified in the high risk group for developing pe. ctpa findings confirmed pe diagnosis for 60 (31.7%) patients (6.7% high risk, 75.0% moderate risk, 18.3% low risk). d-dimer test was only ordered for 27 patients, 25 (92.6%) of which were positive. among the patients with positive d-dimer, 18 (72.0%) cases had negative ctpa. inactivity (57.4%), hypertension (32.8%), and history of cancer (29.5%) were the most common risk factors of thrombosis in patients with pe. in addition, shortness of breath (60.1%) and tachypnea (11.1%) were the most common clinical findings among patients with pe. there was no significant difference between the patients with pe diagnosis and others regarding mean age (p = 0.560), sex distribution (p = 0.438), and type of thrombosis risk factors (p > 0.05), hospitalization department (p = 0.757), wells’ score (p = 0.665), electrocardiography findings, or blood gas analyses. conclusion: although attention to thrombosis risk factors, clinical symptoms, and laboratory findings, can be helpful in screening patients with suspected pe, considering the ability of ct scan in confirming or ruling out other possible differential diagnoses, it seems that a revision should be done to lower the threshold of ordering this diagnostic modality for suspected cases. keywords: pulmonary embolism; computed tomography angiography; diagnosis; risk factors; signs and symptoms; symptom assessment cite this article as: bozorgmehr r, pishgahi m, mohaghegh p, bayat m, khodadadi p, ghafori a. relationship between thrombosis risk factors, clinical symptoms, and laboratory findings with pulmonary embolism diagnosis; a cross-sectional study. arch acad emerg med. 2019; 7(1): e41. ∗corresponding author: mehdi pishgahi; cardiology department, shohadaye tajrish hospital, shahrdari street, tajrish square, tehran, iran. email: mpishgahi.cr@gmail.com, tel: 00989123387486 1. introduction pulmonary embolism (pe) is a common and potentially life threatening disease. in population-based studies, incidence rate of pe adjusted for age and sex has been estimated to be 21 to 69 patients in each 100000 population per year (1, 2). on the other hand, pe is the cause of 1.3% to 10% of all this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 2 in-hospital deaths (3-5). a relatively considerable number of pe and deep vein thrombosis (dvt) cases currently occur in orthopedics, gynecology, surgery, urology, and . . . departments, which seem preventable. due to the high rate of mortality due to pe (up to 30%), timely initiation of proper treatment can lead to a decrease in mortality by up to 8% (6). accurate and timely diagnosis of pe is still a challenge faced by physicians. due to presence of a wide range of nonspecific symptoms such as chest pain, hemoptysis, and dyspnea, accurate and rapid diagnosis of pe can be mistaken with other differential diagnoses. in 75% of patients with suspected primary symptoms, pe is confirmed in final evaluations (7). the results of a meta-analysis showed that clinical symptoms alone have 85% sensitivity and 51% specificity for diagnosis of this disease (8). therefore, having strong clinical suspicion is vital for diagnosis of the disease and not missing true cases. among diagnostic methods, computed tomography pulmonary angiography (ctpa), is the best imaging method and is necessary for definite diagnosis (9). of course, this valuable diagnostic modality is not available everywhere and in addition to imposing costs on the patient and healthcare system, it is also associated with unavoidable side effects such as radiation and probability of reaction to radio contrast agent. currently simple and available tools, such as arterial blood gas analysis, electrocardiography (ecg) findings, and clinical decision rules such as wells’ score have been considered for help in triage of suspected cases. however, a consensus regarding their diagnostic value and screening performance characteristics for the mentioned purpose has not been reached, yet. considering the afore-mentioned points, the present study has been designed with the aim of evaluating the relationship between risk factors, clinical symptoms, and laboratory findings with the ctpa confirmed pe. 2. methods 2.1. study design and setting in the present retrospective cross-sectional study, all patients with suspected pe who were hospitalized in different departments of shohadaye tajrish hospital, tehran, iran, during 1 year and underwent ctpa were evaluated. protocol of the study was approved by the research council and ethics in research committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.retech.rec.1397.546). the checklist for data gathering was filled out anonymously using medical profile codes for each patient with suspected pe. 2.2. participants patients suspected to pe hospitalized in different departments (internal medicine, surgery, intensive care, oncology, and . . . ) of the mentioned hospital who had undergone ctpa and their clinical profile was available were included in the study. no age or sex limitation was considered for inclusion in the study. patients with missing data in their clinical profile were excluded from the study. 2.3. data gathering for gathering data, a checklist consisting of demographic data (age, sex), known risk factors of thrombosis (history of cancer, obesity, trauma, and . . . ), clinical findings (shortness of breath, tachycardia, tachypnea, hemoptysis, and . . . ), laboratory parameters (d-dimer, blood gas analysis), the result of ctpa, electrocardiographic (ecg) manifestations, risk of developing pe based on wells’ score (high risk, low risk, and moderate risk), as well as outcome (death and survival) was filled out for all patients by referring to their clinical profile. checklists were anonymous and filled using the profile code for each patient. a trained intern was responsible for data gathering under direct supervision of an internal medicine specialist. all ctpas had been evaluated and interpreted by the radiology department of the hospital regarding presence or absence of pe. 2.4. statistical analysis patients’ data were entered to spss version 23 statistical software. quantitative data were described using mean and standard deviation (sd) and qualitative data were described using frequency and percentage. to determine if the data was normal or not, kolmogorov-smirnov test was used. if quantitative data had normal distribution, independent t-test was used; and otherwise, non-parametric equivalent test (mannwhitney u test) was applied. to evaluate the correlation between qualitative variables, chi-square and fisher’s exact tests were used. all analyses were performed with an alpha error of 5%. 3. results 188 patients with the mean age of 61.91 ± 18.25 (20 – 101) years were studied (54.8% male). table 1 shows the baseline characteristics of the studied patients. the highest number of cases with suspected pe belonged to internal medicine (33.9%), surgery (30.5%), and intensive care (14.1%) departments. mean wells’ score of the patients was 3.88 ± 1.15 (0 – 9). based on wells’ score, 32 (17.2%) patients were in the low risk group, 145 (78.0%) were in the moderate risk, and 9 (4.8%) patients were classified in the high risk group for developing pe. ctpa findings confirmed pe diagnosis for 60 (31.7%) patients (6.7% high risk, 75.0% moderate risk, 18.3% low risk). d-dimer test was only ordered for 27 patients, 25 (92.6%) of which were positive. among the patients with posthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e41 table 1: baseline characteristics of the studied patients variables total (n = 188) confirmed pe p value no (n = 127) yes (n = 60) age (years) mean ± sd 61.91 ± 18.25 61.39 ± 18.71 63.02 ± 17.37 0.56 sex (%) male 85 (45.5) 60 (47.2) 25 (41.0) 0.438 female 103 (54.8) 67 (52.8) 36 (59.0) thrombosis risk factors history of dvt 6 (3.2) 5 (3.9) 1 (1.6) 0.666 obesity 5 (2.7) 3 (2.4) 2 (3.3) 0.660 history of cancer 53 (28.2) 35 (27.6) 18 (29.5) 0.863 hypertension 65 (34.6) 45 (35.4) 20 (32.8) 0.721 ocp or hrt 2 (1.1) 1 (0.8) 1 (1.6) 0.545 copd 7 (3.7) 4 (3.1) 3 (4.9) 0.684 pregnancy 1 (0.5) 1 (0.8) 0 (0) 1.000 recent surgery 33 (17.6) 24 (18.9) 9 (14.8) 0.544 thrombophilia 0 (0) 0 (0) 0 (0) na trauma history 31 (16.5) 18 (14.2) 13 (21.3) 0.217 inactivity 103 (54.8) 68 (53.5) 35 (57.4) 0.621 recent travel 1 (0.5) 0 (0) 1 (1.6) 0.148 clinical symptoms chest pain 15 (7.9) 10 (7.8) 5 (8.3) 0.891 dyspnea 112 (59.6) 76 (58.9) 36(60.1) 0.888 tachycardia 14 (7.5) 9 (7.0) 5 (8.3) 0.740 tachypnea 20 (10.7) 13 (10.1) 7 (11.7) 0.741 hemoptysis 2 (1.1%) 2 (1.6) 0 (0) 0.323 wells’ score high risk 9 (4.8) 5 (55.6) 4 (44.4) moderate risk 146 (78.1) 101 (69.2) 45 (30.8) 0.665 low risk 32 (17.1) 21 (65.6) 11 (34.4) outcome survived 139 (73.9) 94 (74.0) 45 (73.8) 0.971 not survived 49 (26.1) 33 (26.0) 16 (26.2) data are presented as mean ± standard deviation (sd) or number (%). na: not applicable. dvt: deep vein thrombosis, ocp: oral contraceptive, hrt: hormone replacement therapy; copd: chronic obstructive pulmonary disease; pe: pulmonary embolism. table 2: electrocardiogram (ecg) manifestations and blood gas analysis of the studied subjects variables total (n = 188) confirmed pe p value no (n = 127) yes (n = 60) ecg manifestation sinus tachycardia 105 (55.9) 73 (57.5) 32 (52.5) 0.516 atrial fibrillation 10 (5.3) 8 (6.3) 2 (3.3) 0.338 s1q3t3 pattern 48 (25.5) 32(25.2) 16 (26.2) 0.879 t inversion in v1-3 34(18.1) 20(15.7) 14 (23) 0.230 right bundle brunch block 20 (10.6) 13 (10.2) 7 (11.5) 0.796 arterial blood gas analyses o2 saturation (%) 84.97 ± 15.45 85.66 ± 15.73 83.54 ± 14.86 0.131 ph 7.40 ± 0.08 7.40 ± 0.09 7.38 ± 0.06 0.145 pco2 (mmhg) 46.32 ± 12.98 49.56 ± 15.70 39.59 ± 2.68 0.893 hco3 (mmhg) 22.62 ± 7.43 22.55 ± 6.41 22.75 ± 9.27 0865 po2 (mmhg) 66.04 ± 36.80 69.42 ± 38.97 58.93 ± 38.95 0.162 data are presented as mean ± standard deviation (sd) or number (%).pe: pulmonary embolism. itive d-dimer, 18 (72.0%) cases had negative ctpa. inactivity (57.4%), hypertension (32.8%), and history of cancer (29.5%) were the most common risk factors of thrombosis incidence in patients with pe. in addition, shortness of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 4 breath (60.1%) and tachypnea (11.1%) were the most common clinical findings among patients with pe. there was no significant difference between the patients with pe diagnosis and other patients regarding mean age (p = 0.560), sex distribution (p = 0.438), type of thrombosis risk factors (p > 0.05), hospitalization department (p = 0.757), and wells’ score (p = 0.665). table 2 depicts ecg findings and blood gas analyses of the studied patients. sinus tachycardia (52.5%), s1q3t3 pattern (26.2%), and t inversion (23.0%) were the most common findings in the ecgs of patients with pe. however, there was no significant difference between the pe group and other patients regarding ecg findings and blood gas analyses. sensitivity, specificity, positive and negative predictive values of wells’ score with 95% confidence interval (ci) in these patients were 31.61% (95% ci: 24.51 – 39.63), 65.62% (95% ci: 46.77 – 80.82), 81.86 (95% ci: 69.14 – 90.06), and 16.53 (95% ci: 10.75 – 24.39), respectively. the accuracy of wells’ score based on area under the receiver operating characteristic (roc) curve was estimated as 0.509 (95% ci: 0.420 – 0.598). 4. discussion based on the results of the present study, the prevalence of pe among the studied patients was estimated to be about 32%. there was no significant difference between patients with confirmed diagnosis of pe and other suspected cases regarding age, sex, clinical symptoms, laboratory findings, ecg manifestations, hospitalization department, and wells’ score. in a meta-analysis, moores et al. reported the prevalence of pe as 15% 37% based on the results of ctpa (8). this rate was estimated as 17.1% in the study by abidi et al. and about 60% in the study by sodhi et al. (10, 11). in the present study, no significant statistical correlation was observed between pe diagnosis and risk factors, clinical symptoms, or laboratory findings. based on esc guidelines on the diagnosis and management of acute pe, 2014 in evaluating differential diagnoses of pe, no symptom alone can rule out this diagnosis and clinical symptoms such as shortness of breath, tachycardia, tachypnea, chest pain, and hemoptysis are non-specific for diagnosis of pe (12). in the preset study, the most common cardiac findings in the ecgs of the patients with pe were sinus tachycardia, followed by s1q3t3 pattern and t inversion. in our evaluation, there was no statistically significant difference between patients with and without pe regarding ecg findings. numerous studies have evaluated the use of ecg and its ability to diagnose pe (13, 14). in the study by sinha et al. sinus tachycardia, s1q3t3 pattern, atrial tachyarrhythmia, presence of q wave in lead iii and q3t3 pattern were among the findings related with pe. sinha et al. expressed that these findings are generally non-specific and mostly change throughout time and may worsen the outcome of pe in some cases (14). they reported that classic s1q3t3 pattern lacked the required specificity in diagnosis and prognosis determination of pe. however, a study performed by bircan et al. showed that after confirming diagnosis of pe, using ecg findings can be helpful in differentiation of massive pe from non-massive cases (15). t invert is another finding in v1-v4 leads in ecg, which was found in 23% of patients with pe. in a prospective study, it has been shown that inversion of t wave is the most common ecg abnormality in precordial leads of patients with pe, which correlates with severity and volume of the embolism (15, 16). in the study performed by bircan et al. it was shown that nearly all of the abnormal ecg findings in pe patients were associated with severe pe (15). it seems that although ecg findings do not have the required power for confirming or ruling out pe diagnosis, they can be helpful in triage of the patients and determining the severity of disease. regarding arterial blood gases, groups of patients with and without pe did not show a significant difference regarding arterial blood gas indices such as o2 pressure and co2 pressure. these findings were in line with the results of the study carried out by rodger et al. who showed that using arterial blood gas indices does not have the required ability to confirm or rule out pe diagnosis (17). this finding was also confirmed by other researchers such as matsuoka et al. (18). however, other researchers have shown that using arterial blood gas indices along with other diagnostic methods such as d-dimer has acceptable negative predictive value in ruling out pe diagnosis (17). metafratzi et al. found a strong correlation between angiography obstruction and blood gas rates in pe patients. in the study, it was expressed that paco2 rate being 30 mmhg or lower was indicative of an obstruction index higher than 50% in the pulmonary arterial bed to a great extent (19). in another study, it was also shown that measuring arterial-alveolar o2 pressure slope is one of the simple and very useful methods for predicting short term prognosis in patients with acute pe (20). masotti et al. also showed that there is a significant correlation between mortality rate among pe patients with decrease in o2 saturation and metabolic acidosis (21). in this study, the highest number of suspected pe cases belonged to internal medicine, surgery, and intensive care departments, respectively. in the study by abidi et al. the highest number of suspected pe cases belonged to emergency, surgery, and intensive care departments (10). based on the results of salanci et al. study, most referred pe cases were from internal medicine and surgery departments, which is in line with the results of our study (22). overall, although using clinical symptoms and ecg findings as well as evaluating arterial blood gas indices can help in diagnosis of pe in suspected patients, in our retrospective evaluation, no significant difference was found between the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e41 groups with and without pe in these regards. further studies should be carried out with the aim of assessing the diagnostic value of these indices along with other clinical and laboratory methods. 5. limitation having a retrospective design was among the limitations of the present study as it limited the ability to accurately assess the risk factors as well as the clinical symptoms in patients with suspected pe. extraction of patients’ data from the history recorded in their profiles and not being able to evaluate the precision and accuracy of the recorded data was sometimes problematic for interpretation of the findings. performing more comprehensive studies with prospective design and in multiple centers is suggested for more accurate evaluation of clinical and laboratory symptoms of patients with suspected pe. 6. conclusion although attention to thrombosis risk factors, clinical symptoms, and laboratory findings, can be helpful in screening patients with suspected pe, considering the ability of ct scan in confirming or ruling out other possible differential diagnoses, it seems that a revision should be done to lower the threshold of ordering this diagnostic modality for suspected patients. 7. appendix 7.1. acknowledgements hereby, all the staff members of internal medicine, surgery, intensive care, and emergency departments of shoahadaye tajrish hospital who helped us in performing this study are thanked. 7.2. authors’ contribution all authors met the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids rama bozorgmehr: 0000-0003-4221-0316 mehdi pishgahi: 0000-0002-1196-6535 pegah mohaghegh: 0000-0001-5679-9796 7.3. funding/support no financial support has been received for this project. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. richman pb, courtney dm, friese j, matthews j, field a, petri r, et al. prevalence and significance of nonthromboembolic findings on chest computed tomography angiography performed to rule out pulmonary embolism: a multicenter study of 1,025 emergency 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carrier m, jones gn, rasuli p, raymond f, djunaedi h, et al. diagnostic value of arterial blood gas measurement in suspected pulmonary embolism. american journal of respiratory and critical care medicine. 2000;162(6):2105-8. 18. matsuoka s, kurihara y, yagihashi k, niimi h, nakajima y. quantification of thin-section ct lung attenuation in acute pulmonary embolism: correlations with arterial blood gas levels and ct angiography. ajr american journal of roentgenology. 2006;186(5):1272-9. 19. metafratzi zm, vassiliou mp, maglaras gc, katzioti fg, constantopoulos sh, katsaraki a, et al. acute pulmonary embolism: correlation of ct pulmonary artery obstruction index with blood gas values. ajr american journal of roentgenology. 2006;186(1):213-9. 20. hsu jt, chu cm, chang st, cheng hw, cheng nj, ho wc, et al. prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism. circulation journal : official journal of the japanese circulation society. 2006;70(12):1611-6. 21. masotti l, ceccarelli e, cappelli r, barabesi l, forconi s. arterial blood gas analysis and alveolar-arterial oxygen gradient in diagnosis and prognosis of elderly patients with suspected pulmonary embolism. the journals of gerontology series a, biological sciences and medical sciences. 2000;55(12):m761-4. 22. salanci bv, kiratli po, demir a, selcuk t. risk factors of pulmonary thromboembolism in patients from a university hospital. saudi med j. 2007;28(4):574-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e74 rev i ew art i c l e the potential role of super spread events in sars-cov-2 pandemic; a narrative review anthony m. kyriakopoulos1∗, apostolis papaefthymiou2,3, nikolaos georgilas4, michael doulberis3,5, jannis kountouras3 1. department of research and development, nasco ad biotechnology laboratory, piraeus 18536, greece. 2. department of gastroenterology, university hospital of larisa, larisa 41110, greece. 3. department of internal medicine, second medical clinic, ippokration hospital, aristotle university of thessaloniki, thessaloniki, 54642 macedonia, greece. 4. department of nephrology, agios pavlos hospital of thessaloniki, thessaloniki 55134, macedonia, greece. 5. division of gastroenterology and hepatology, university medical department kantonsspital aarau, aarau 5001, switzerland. received: august 2020; accepted: august 2020; published online: 21 september 2020 abstract: coronaviruses, members of coronaviridae family, cause extensive epidemics of vast diseases like severe acute respiratory syndrome (sars) and coronavirus disease-19 (covid-19) in animals and humans. super spread events (sses) potentiate early outbreak of the disease and its constant spread in later stages. viral recombination events within species and across hosts lead to natural selection based on advanced infectivity and resistance. in this review, the importance of containment of sses was investigated with emphasis on stopping covid-19 spread and its socio-economic consequences. a comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of sses on severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic" and were published before 20th of august 2020. overall, ninety-eight articles were found eligible and reviewed. specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (sars-cov-2) epidemics, in contrast to the partially effective general restriction measures. the effect of sses on previous sars epidemics has been documented in detail. however, the respective potential impact of sses on sars-cov-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective sse preventive strategies, which may lead to overt global community health benefits. this is crucial for sars-cov-2 pandemic containment as the vaccine(s) development process will take considerable time to safely establish its potential usefulness for future clinical usage. keywords: pandemics; epidemics; coronavirus; severe acute respiratory syndrome coronavirus 2; disease outbreaks; cost of illness; mass vaccination cite this article as: kyriakopoulos am, papaefthymiou a, georgilas n, doulberis m, kountouras j. the potential role of super spread events in sars-cov-2 pandemic; a narrative review. arch acad emerg med. 2020; 8(1): e74. 1. introduction severe acute respiratory syndrome (sars) has periodically emerged as epidemics and its natural history could be utilized as a "compass" to comprehend and manage the current pandemic of sars-cov-2. sars-cov-2 the etiologic agent of the novel coronavirus disease 2019 (covid-19), be∗corresponding author: anthony m. kyriakopoulos; department of research and development, nasco ad biotechnology laboratory, 11 sachtouri str, piraeus 18536, greece. email: antkyriak@gmail.com, fax : 00309210818032 longs to rna coronavirus family (coronaviridae) and is a zoonotic coronavirus that has crossed species barriers to infect human (1-3). the initially investigated strains of covid19 exhibited low potential for transmissibility and infectivity, similar to sars coronavirus (sars-cov ) (1-4). moreover, sars epidemic was potentiated due to super spread events (sses), which led to unexpected elevation of the basic reproduction numbers as calculated via associated epidemiology equations (5). specifically, sses resulted from secondary contacts of carriers (6, 7). infected individuals, as mediators of sses, represent the initial cluster of viral transmission (8); thus, inducing an exponential secondary contamination (4). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. m. kyriakopoulos et al. 2 although the prediction and subsequently the prevention of sses seems to be complicated, the virus, host, environmental, and mass behaviors determine relative approaches to prevent and control sses; core community health programs can inhibit and decrease the incidence and the effect of sses (9). nevertheless, horizontal austerity measures, such as recommending or compelling individuals to self-isolate at home, which might cause serious social and psychological burden, and quarantine, also leading to loss of income due to social distancing, are associated with negative psychological and religious effects, which can be long lasting (10), thereby leading to serious instability of the global society. prolonged social isolation and loneliness are associated with increased mortality (11). currently, limited piece of information exists regarding the effect of sses on coronavirus epidemics. the aim of this narrative review is to mainly focus on the potential impact of sses on large outbreaks of coronavirus. the development of an emergency sars-cov-2 vaccine has its potential usefulness and/or limitations and may result in severe health outcomes, which prompts better screening for sses in order to control coronavirus pandemics. 2. method 2.1. methodological approach to avoid, in most respects, literature selection bias (12), multiple electronic sources: medline/pubmed, scifinder, science direct and goggle scholar as well as researchgate and general (google) were investigated via queries with a nonrestricted time frame reaching the 20th of august 2020. initial investigation of sses and sars, sses and mers, and sses and covid-19, gave narrative results from pubmed. the selected literature, which is included in the study, is presented in table 1. same items were also searched in all other mentioned sources. the scope of the study was not only to investigate the transmission of sars-cov-2 due to sses, its comparison with sars-cov-1 and mers-cov, but also to assess the general global impact due to sses by covid-19. therefore, further literature investigation was performed using the same electronic sources. further investigation was made on: a) the prevention of sses by coronaviruses causing sar-1, mers and covid-19, b) the socio-economic relation of sars-cov-1, mers and covid19 due to sses, c) the austerity caused by sses of covid19, and d) the relation of sses containment to future vaccination programs. for further investigation, the following items were searched: "sars, mers and covid-19 epidemic prevention", "sars mers and covid-19 infectivity and pathogenicity", "coronavirus sse prevention", sse coronavirus crisis and socio-economics", "holy cup religion and transmission of pathogens and sses", and "coronavirus immunity and vaccination". 2.2. selection process screening process and eligibility criteria studies providing an adequate determination of an sse related to sars, mers and covid-19 were primarily screened and selected by two reviewers (authors) blinded to one another. the results were thereafter cross-matched and duplicates were removed. based on this primary search, the socio-economic impact of coronavirus, produced by sses, was extrapolated by two other reviewers (authors). following this initial selection stage, further screening was performed by all reviewers, using the previously described search items to identify parameters determining the global impact of covid-19 due to sses. identified parameters included the global impact of immunity and vaccination, the holy cup and religion transmission, and the austerity caused by covid-19 and other coronavirus epidemics due to restrictions applied. all search results were cross-matched to remove duplicates and thereafter, exclusion and inclusion criteria were applied. exclusion and inclusion criteria after removing the duplicates, review was conducted on titles and abstracts. also, a decision was made to remove "news press opinions". computational model methodologies producing contradictory results, studies with wrong interpretation of sses, and studies with non-clear-cut results were also removed. studies using the interpretation "a super spreading individual, known as the index case, produces a cluster of sars, mers, and covid-19 secondary infections" were included. a second exclusion criterion was applied. in this stage, peer reviewed literature of recent dates, studies assessing sars, mers, and covid-19 epidemiology measures, studies on covid-19 restriction measures producing social and economic austerity, articles discussing the perspective for future vaccination and population immunity, and finally genetic studies on coronaviruses causing sars, mers, and covid-19. 3. results by following the described methodology, on medline/pubmed: a) 23 articles were found on sars and mers and sse, and b) 11 articles were found on covid-19 and sses. out of: a) 13 of the 23 articles on sars and mers and sse, and b) 7 out of the 11 articles on covid-19 and sse were deemed relevant hits. after applying the exclusion criteria, 12 articles from the first category, and 4 from the second category were included in the study. suitable articles found by searching, which were selected and reviewed for each part, are illustrated in figure 1. further investigation in all other electronic sources described, using the same methodthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e74 table 1: literature included from pubmed search for sses* in relation to coronavirus outbreaks literature included in review for sars∧ and mers! in relation to sses* authors and year type of article** study description chowell et al. (2015)(51) comparative research investigation of relation between sses for sars and mers transmission in nosocomial outbreaks al tawfig et al. (2020) (38) commentary demonstration of a stochastic model of transmission of sars virus shaw (2006) (55) perspective review implementing efficient intensive care practices to avoid hospital transmission chen et al. (2006) (96) original research case control study investigation of sse likelihood during hospital transmission sung et al. (2009) (97) original research case control study investigation of sses occurring in hospital and prevention strategies li et al. (2004) (54) original research case control study investigation of factors contributing to sses for prevention and control of disease riley (2003) (5) original research cross sectional study analysis of sars epidemiology in hong kong stein (2011) (98) perspective review analysis of sars transmission leading to sse gormely et al. (2017) (52) original research model for prevention of pathogen transmission via sanitary plumping systems lau (2004) (53) perspective review implementation of sse containment with vaccination programs literature included in review for covid-19 in relation to sses cave (2020) (56) perspective review call for clear epidemiologic definition for sses xu (2020) (57) original research retrospective cohort study analysis of sses during covid-19 in china kwok (2020) (58) original research analysis of sse influence in the nature of covid-19 epidemic zhang (2020)(21) original research description of sse importance in covid-19 epidemic ! severe acute respiratory syndrome; ∧ middle east respiratory syndrome; &coronavirus disease-19; *super spread events; **when clearly indicated in article, the type of study is also mentioned. table 2: the search results of literature related to covid-19& global impact due to sses* search item medline/pubmed other electronic sources** number of articles retrieved number of articles included sars!, mers∧, and covid-19 epidemic prevention 42 3589 139 17 sars, mers, and covid-19 infectivity and pathogenicity 672 3812 145 18 coronavirus sse prevention 10 627 151 22 sse, coronavirus crisis, and socio-economics 4 3181 89 11 holy cup religion and transmission of pathogens and sses 0 15 4 4 coronavirus immunity and vaccination 73 20975 1175 9 &coronavirus disease-19; *super spread events; ** science direct, scifinder, and google scholar; !severe acute respiratory syndrome; ∧middle east respiratory syndrome ology, increased the number of the included literature to a) 17 and b) 14, for their respective categories of search. studies included from pubmed in these categories of searches are briefly described and listed in table 1. further, assessing the general global impact of sses related to covid-19, using all the mentioned sources, via the same methodology, led to the inclusion of a) 10 articles related to genetic analysis of sarscov-1 and mers-cov and sars-cov-2, b) 5 articles related to super spread events, c) 2 articles related to austerity, d) 18 articles related to infectivity and pathogenicity of sars, mers and covid-19, e) 17 articles related to prevention of sses concerning human coronaviruses, f ) 9 articles related to socio-economic impact, and g) 9 articles related to immunity and future vaccination. table 2 illustrates the initial numbers of hits using all search items in all sources, and the final number of articles reviewed in each category. 4. discussion 4.1. insights to sses the involvement of sses in sars extensive outbreaks (1, 4, 5, 13-17), necessitates urgent elucidation as global tranquility is this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. m. kyriakopoulos et al. 4 figure 1: method followed for pubmed search and literature selection regarding sse in relation to a) sars-1, mers and b) covid-19 outbreaks. disturbed by covid-19 pandemic. epidemiological research has proposed that the outbreak was related to a seafood market in wuhan (hubei, china), underlining the ongoing risk of viral transmission from animals to induce severe diseases in humans. metagenomic rna sequencing of bronchoalveolar lavage fluid from a patient with pneumonia identified a novel rna virus strain from the coronaviridae family (called sars-cov-2); and phylogenetic analysis (by introducing the widely used in silico protein screening) (18-21) of the complete viral genome (29,903 nucleotides) disclosed that the virus was most closely connected (89.1% nucleotide similarity) with a group of sars-like coronaviruses (genus betacoronavirus, subgenus sarbecovirus) formerly isolated from bats in china (18-22). insights from previous reports by menachery et al. (23) (menachery et al., 2015), pointed out that the 2002-2003 emergence of sars-cov introduced the possibility of viruses of animal origin causing epidemics in human populations. conclusions from their study revealed, as previous studies had demonstrated (1, 5, 13, 15), that closely related sars-like viral genes were traceable in chinese bat populations. authors claimed that these viruses were capable of infecting humans, by selective adaptations or adjustments, and thereby, causing a new epidemic (23). enhancement of virulence is also attributed to these adaptations due to acquisition of spike protein via adaptive mutations (24). continuous viral random mutations are possible through inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e74 figure 2: flow of genetic variation of coronaviruses leading to increase of virulence and pathogenicity; epidemiologic steps for specific and targeted diagnosis to prevent super spread events. blue arrows point to the flow of genetic variation across gene pools where genetic variation occurs, i.e. a) between hosts of the same species, b) between hosts of different species by crossing the species barrier, spreading to c) humans and subsequently to super spreader individuals, where disease transmission is potentiated. grey arrows point to specific identifications that can lead to effective interventions with the potential to control the disease spread. termediate host transmission, until a deadly virus develops, as illustrated in figure 2. recent evidence revealed that recombination within intermediate hosts has contributed to development of sars-cov-2 (1, 24). asian outdoor markets could constitute the ideal places for continuous viral mutation exchanges (25). as presented in table 3, the best way to circumvent continuous virus production is targeted surveillance; to at least stop the overspreading by sses (2, 3, 22, 26). this has also been proposed by menachery et al. (23). 4.2. sars epidemics and sars-cov-2 pandemic sars-cov-2 is accountable for the unprecedented covid19 pandemic (27), and the interplaying mechanisms involved in the pathophysiology of covid-19 include sars-cov-2 virulence, host immune response, and complex inflammatory reactions (28). emerging data, also, imply that the reservoirs of sars-cov-1 infection may be similar to covid-19 (1, 4, 5, 13, 29), as remarkable similarities exist between sars and swine acute diarrhea syndrome (sads) in topographical, temporal, environmental and etiological backgrounds. however, the increasing coronavirus variety and spread in bats were recognized as a potential target to diminish future epidemics that might impend livestock, community health, and financial progress (30). probably, identification of animal and insect vectors that transmit the disease, identification and control of alternative routes of transmission like fecal-oral route, and identification of super spreader patient groups could help minimize the epidemiological extent compared to the one observed for sars-cov-2 infection worldwide. lessons from sars epidemic taught us that the key to control is minimizing the time from the diagnosis of infection to prompt hospital isolation and diminishing the probability this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. m. kyriakopoulos et al. 6 table 3: key clinical and laboratory screening functions to appropriately forecast, prevent, and confront sars! coronavirus 2, and future coronavirus epidemic waves specific clinical and laboratory investigation validated techniques to be used forecasting of pre-symptomatic infection to estimate the probability of a major outbreak, use simulations of stochastic compartmental epidemic models. use of diagnostic tests to detect asymptomatic susceptibility and pre-symptomatic infectivity estimation of super spread events of current and previous coronavirus epidemics introduction of individual reproductive number. integrated and computational analysis of the influence of individual variation by binomial distribution and use of branching process analysis of disease data. genetic characterization of inpatient viral isolates to identify intermediate animal hosts facilitating the infection next generation sequencing of samples and cultured viral isolates to obtain full sequence and phylogenetic analysis application. environmental detection and continuous sewage monitoring rt-qpcr# screening on sewage systems, vectorsùĺ and potential air transmission. autopsies and detection of serology conversion of potential vectors. heptad repeat region screening for positive selection computer simulation models to detect positive selection events e.g. codeml branch-site test coupled with bayes empirical bayes procedure, and mixed effects model of evolution. receptor recognition analysis of ace-ii+ to identify origin of crossspecies and human to human transmissions coronaviruses genetic sequencing and phylogenetic analysis of ace-ii to provide origin and efficiency of cross-species and human to human transmission and identification of intermediate hosts. !severe acute respiratory syndrome; #reverse transcriptase quantitative polymerase chain reaction; +angiotensin-converting enzyme-ii. table 4: potential groups of coronavirus super spreaders within the human population* population group potential route of transmission hepatitis b and c virus positive patients airborne pulmonary tuberculosis positive patients airborne hiv! positive patients airborne, urine & fecal-oral (98) patients receiving hemodialysis airborne (droplets by nebulizer) and fecal-oral mrsa# staphylococcus aureus acquisition constant worn glove contact transmission rhinovirus co-infections airborne gastrointestinal (salmonella enteritis) co-infections fecal – oral frequent contact with wild animal reservoirs (including domestic animals) and birds** airborne and fecal – oral construction area workers air particles sewage system workers*** fecal – oral *in both community and hospital environments. **including slaughter houses, pet shops, animal and bird collectors and breeders, cow, and pig farmers. ***including workers coming in contact with environment contamination. !human immunodeficiency virus, #methicillin resistant staphylococcus aureus. of another sse (5). 4.3. the 20/80 rule as applied to sars the typically recognized 20–80 rule or the so-called "pareto rule", states that 20% of efforts lead to 80% of results (31). more specifically, this comprises a principally convenient state when tackling infectious diseases and is applied to investigate infection transmission, and initially among cattle farms. in this regard, woolhouse et al. (17) reported that targeted actions concerning disease control and prevention in 20% of the farms that mainly supplied the basic reproduction number (ro) decreased spread by 80% (32). focusing on the covid-19 virus, ro is a sign of virus transmissibility, denoting the average figure of novel infections caused by an infectious individual in a totally naive population. for r0 > 1, the number of infected people tends to increase, whereas for r0 < 1, transmission is likely to stop; ro represents a chief model in the epidemics, signifying the risk of an infectious mediator with regard to epidemic spread (33). recent data indicate that the estimated mean ro for covid-19 is almost 3.28, with a median of 2.79 and the interquartile range (iqr) of 1.16, which is substantially higher than who’s estimation of 1.95. however, due to biased methodology, ro for covid-19 is expected to be about 2–3, which is approxithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e74 mately consistent with the who estimate (33). sses appear to be a main limitation of the ro concept. ro, when calculated as a mean or median value, does not include the heterogeneity of transmission between infected individuals (4); two infective agents with equal r0 estimates might have noticeably diverse patterns of transmission. moreover, the goal of a health care system is to achieve ro <1, which is probably only phenomenally feasible in certain conditions without scheduled prevention, recognition, and response to sses (9). naturally, epidemics follow the aforementioned 20 / 80 rule (17). specifically, in human population, due to heterogeneous exposure to infectious agent, the 20% core population may transmit the disease, widely. for sars, the rate might have been even lower than 20% (4). the increased infectious potential of a small population subgroup seems to be related to immunodeficiency, such as in hemodialysis, cancer, immunosuppressive therapies (4, 5, 15, 34). additionally, facilitation of disease spread and transmission due to vector exposure has been investigated in relation to cockroaches (35). possible mechanical transportation by rats and cat (13, 36) and air transmission (37) in sars-cov-1 have also been studied. other animals capable of being sars-cov-2 carriers (excluding mice and rats), like pigs, ferrets, cats, and nonhuman primates have recently been introduced (3), and contamination of sewage with sars-cov-2, has probably preceded covid-19 outbreak in france (29). all these agents may contribute to a minimum of 80% of the total transmission potential (17), maybe even more (4, 5). table 4 displays possible super spreader groups; thus, indicating screening targets to prevent sses. sars epidemic taught us that control programs were inefficient in controlling the epidemic within a population, and failed to identify and provide a targeted infection diagnosis in groups causing potential sses (5, 17). on the other hand, sars-cov-2 having the ability to cause a pandemic rather than an epidemic, resulted in an increased number of cases and deaths; albeit having a lower mortality rate than sars coronavirus (2). sses during covid-19 may involve not only one city, but also a whole country or many countries, requiring investigation of their effects on a national or international level (2, 38, 39). 4.4. prevention of sses preventing and decreasing covid-19-related sses necessitates the decryption of the mechanism through which sarscov-2 spreads through super spreader individuals, for example within healthcare facilities (7, 9). healthcare facilities are essential for prevention and control of sses (9). sse prevention may enable us to even overcome initial low covid-19 virus infectiveness. the capability of the virus to produce sses troubles the epidemiological attempts to restrict viral spread only by isolating individuals at high risk and performing obsolete isolation at home for the general population as carried out in countries such as greece (5). during the sars epidemic in china (beijing) and singapore, the vast majority of infected individuals were barely infective and only 6% of the population was highly infectious, in contrast to many published sars models (4, 5). other ways of potential coronavirus transmission between hosts may provide explanations for enormous outbreaks (16). it should not be disregarded that coronaviruses cause both respiratory and intestinal infections and share common evolutionary roots with hepatitis viruses (40, 41). passing the cross-species barrier and genetic adaptation within hosts may promote virulence of coronaviruses in humans (14). this, prompts to specifically identify potential super spreader groups within populations through targeted diagnosis. some of these groups are listed in table 2. for this purpose, a usual infection must be distinguished from a super spread infection (4, 5). during sars epidemic, the coronavirus infectiousness mostly occurred in the late stages of infection (5, 17), whereas in covid-19, viruses are transmitted even in pre-symptomatic stages (42). as with influenza a virus subtype h1n1 transmission (43), accurate diagnosis of covid-19 in potentially asymptomatic super spreaders may help contain the magnitude of large outbreaks (44). in the case of diamond princess cruise ship, an earlyassessed r0 of 14.8 (âl’́l4 times higher than the r0 in the epicenter of the outbreak in wuhan, china) was decreased to an assessed effective ro of 1.78 following on-board isolation and quarantine processes (45). similarly, in china (wuhan) the application of non-pharmaceutical interventions in the society, including a cordon sanitaire of the town; interruption of community transport, school, and most employment; and termination of all community events decreased the ro from 3.86 to 0.32 over a 5-week period (46). nevertheless, these strategies could not be maintained. emerging research evidence (29) regarding sewage contamination that preceded paris covid-19 epidemic is pointing to the reports of 2003 from the health department of hong kong (35, 36), the noble work by ng (13), and urge for extensive environmental monitoring (29, 37) to prevent future covid-19 relapses. however, the flow of genetic variation may be even more complex as illustrated in figure 2. therefore, advanced clinical and laboratory monitoring is required to prevent sses and thereafter, new coronavirus epidemics. assembly of key functions and screening techniques of reference centers is presented in table 3. newer therapeutic agents and protocol applications are promising (47), although probably carrying the possibility of resistance state (48). first, these also require specific diagnostic and surveillance strategies to overcome any unknown adverse epidemiology consequences (48). inhibiting wild meat markets and related consumption of wild meat by creating vivid campaigns could be a critical for interrupting the introduction of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. m. kyriakopoulos et al. 8 coronaviruses crossing from animals to the human population, as was the case for sars (1, 4, 5) and middle east respiratory syndrome (mers) (49) epidemics, and probably now for covid-19 pandemic (1-3). furthermore, the food production process requires radical reconsideration, concerning the industrial environment of current food production and serious violations of natural ecosystems (50). current industrial procedures for preparing food increasingly favor conditions where viral evolution produces new mutations and increased rates of mutations (25), thus raising the probability of new and more infectious viral strains. in sars and mers epidemics, the role of sses in vigorously distributing the epidemics has been substantially proven (51-55). the new covid-19 epidemiology evidence also adequately highlights the important role of sses in homeland of china (21, 56, 57), although surprising evidence from neighboring countries show the unlikely role of sse in the spread of the disease (58). 4.5. effective molecular screening of sars-cov-2 and socioeconomic relations the coronaviridae family is characterized by a positive-sense single-stranded rna genome. mouse hepatitis virus is a representative member of the family (41). additionally, human hepatitis e virus also has a positive-sense single stranded rna genome and shares a common evolution pathway with coronaviruses (40). hepatitis-related incidents were described for sars (59). the genetic recombination of these viruses within arbitrary intermediate hosts produced contagious strains that are extremely pathogenic to humans (40, 60). in this respect, the relation of sars-cov genetic sequences isolated from human, civets, and bats permitted us to find the reason for such a dangerous epidemic, which affected people on a worldwide scale in 2003 (61). moreover, the unpredictable epidemic of mers-cov posed a serious risk to the health of communities worldwide. these underscored the necessity for further research of the virus epidemiology and pathophysiology to develop successful therapeutic and preventive medications against mers-cov infection (62). while sars-cov-2 is genetically and structurally connected with mers-cov, it has its own exclusive structures which are responsible for its quick spread throughout the world (60). specifically, variations in coronavirus pathogenicity within different species (63) make the understanding of sars epidemics even more unclear through their capability to overcome the barrier for cross species transmission, which also alters their infectivity status (14, 64). as a result, boosting the pathogenic behavior of coronavirus strains, within species (65), and across species barriers (49), which is a reflection of their positive adaptation to rapid recombination events (49). the recent mers epidemic revealed the tendency of the strain to genetically adapt and produce greater outbreaks (49) as occurred in sars epidemic in 2003 (66). however, mainly for socioeconomic reasons, alarm signals were ignored until recently (67). a new phylogenetic analysis technique employed on clustered covid-19 strains displayed a geographic variation preference in infectivity and pathogenesis (39). this is probably due to predominating strain’s tendency to cause an sse as an outcome of a multifactorial epidemic process presented in figure 2 (23, 24). marked sses for covid-19 have already been fully characterized and warrant urgent investigation (23, 24). as presented in tables 3 and 4, each way of transmission should be investigated. heterogeneity of epidemic characteristics across nations (39) implies that in this way we may minimize coronavirus transmission. therefore, salvation of national economic catastrophes will also be achieved in this way (66). thus, the whole biomedical science machinery needs to perform targeted diagnosis of sses and share the obtained experience. subsequently, central authorities will no longer need excessive non-specific contact measures, which will in turn normalize both societal and economic activities. 4.6. sse-related large outbreaks and uncontrolled austerity on the other hand, improper understanding of how covid19 spreads resulted in societal imbalance due to arbitrary restriction of social and religious life including holy communion cup. it has been consecutively demonstrated by expert research that the holy cup (chalice) and the holy cloth are not sources or pathways, for potential spreading of infectious diseases including human immunodeficiency virus (hiv ) (68), hepatitis b virus (hbv ) (69) as well as other communicable pathogens (70). specifically, a review (69), considered other 129 relative studies. in this review, the possibilities that the shared communion cup can act as a vehicle for indirect transmission of human immunodeficiency virus, since it was detected in the saliva of infected individuals, was investigated. it was emphasized that although for bacterial contamination, the alcoholic content of the wine, the material that the cup is made of, or the practice of partially rotating the cup, cannot stop the occasional transmission of microbes, the microbial transmission was considerably reduced by the intervening use of a cloth to swab the lip of the cup between communicants. notably, it was emphasized that transmission means not an obligatory inoculation or infection. furthermore, it was also emphasized that out of the epidemiology of microbes transmitted via saliva, particularly for the transmission of the herpes viruses, the indirect transmission is rare, and indeed transmission is highly possible by other means than by the saliva. it was also emphasized that neither hepatitis b virus nor human immunodeficiency virus infection can be transmitted by saliva, rendering their indithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e74 rect transmission also less likely by inorganic objects. finally, the study concluded that no episode of disease transmission has ever been reported as a result of the shared communion cup use, and that there was not any scientific evidence that the communion cup practice should be abandoned due to the possible risk of spreading of any infection (71, 72). likewise, kingston et al. (68), by considering 44 relative papers, also concluded that there is no evidence that the holy communion cup spreads infections. moreover, more recent estimations also demonstrated that no infections have ever been observed as a result of religious rituals including christian common communion chalice practice (70); whereas, data of previous studies implied that saliva could play a role in hbv transmission, are likely to be trivial (69). similarly, recent evidence indicate that, although hbv dna and hcv rna can be discovered in the saliva of infected patients, they seem unlikely to transmit infection (72). it should be noted that, as in the case of coronavirus (73, 74), hbv also exists in many body fluids including saliva, nasopharyngeal fluid or tears by measures of qualitative and pcr methods (75). the detection of hbv dna in saliva motivated our study group to investigate the potential viral transmission through the holy communion cup. two successive retrospective studies were conducted to investigate the role of holy communion as an independent risk factor of hbv dispersion. the first preliminary study included patients from our registry of those with chronic hepatitis b under entecavir ( jannis kountouras-personal communication) treatment (76), and in the next step, the relative registry of another department of the same hospital was incorporated. other parameters studied, the substantial independent categorical variable to evaluate our hypothesis was the patients’ occupation, thereby introducing two sub-groups; priests and non-priests. this classification was performed based on a standard active and perpetual exhibition (at least once weekly) of priests to many people’s saliva, as a part of the grounded process of the holy communion cup. the control group comprised of the aggregate of orthodox priests in greece (10,338) and the rest general population (10,680,866) at that timeframe. approval of the institutional ethics committee was obtained and all predispositions of the helsinki declaration were fulfilled. the reservoir database did not include any personified information (name, id number, etc.) and thus no informed consent was required. pearson’s chi-squared test with 1 degree of freedom was performed to evaluate whether there was a statistically significant difference between the frequencies of hbv infection in case and control groups and statistical significance was set at p <0.05. the first single-centre registry included 71 patients and one (1.4%) of them was a priest. chronic hepatitis b was significantly more frequent among non-priests compared to priests (x2 (1, n=71)=12.65, p <0.05). the extended sample (n=429) included the registry of another department and an aggregate of four (0.93%) priests were diagnosed with chronic hepatitis b. likewise, the chi-square test revealed that non-priest subjects were more likely to suffer from chronic hepatitis from hbv infection compared to priests (x2 (1, n=429) = 31, p <0.001). in conclusion, both of our analyses indicated a lower prevalence of hbv chronic hepatitis among priests when compared to other occupations. 4.7. coronavirus vaccination and relationship with sses currently, vaccines for covid-19 are in pre-clinical development, and no final clinical phase has been ended due the recent emergence of the disorder. many global entities have stated their plans to produce a vaccine for covid19. according to the who, 41 candidate vaccines are being produced for covid-19 as of march 13, 2020 (77). importantly, for production of highly effective and safe covid19 vaccines, features such as the possibility of the induction of antigen-dependent enhancement (ade) and additional severe opposing effects previously detected with sars and mers should be considered. ade is a phenomenon that occurs when non-neutralizing antibodies against proteins of a virus increase, also increasing virus infectivity (78). in this regard, coronaviruses can escape the immunity provided by inactivated or recombinant protein vaccines via fast evolution (79). the problem with live attenuated vaccines is that the coronavirus can recover its virulence via serial passages in cell culture or in vivo (80). moreover, vaccination in animals and humans could facilitate, rather than inhibit, the pathogenesis of the targeted viruses. this can be the consequence of an ade phenomenon. this underlines a mechanism by which specific antibodies facilitate infection with the targeted virus, or cell-based augmentation, a process resulting in an allergic inflammatory response induced by immunopathology (81, 82). many experimental sars-cov-1 vaccines have been formulated from whole inactivated viruses, due to their advantage of large-scale production, multiple epitope presentation and high conformation stability (83). one such vaccine uses viruses from ay71a217 strain of sars-cov-1, which are double inactivated using formalin and uv irradiation, the socalled double-inactivated virus (div ) vaccine (84). although div had initially been demonstrated to induce neutralizing antibodies and to protect against sars-cov-1 viral replication, both in tissue culture and in young mice, it soon became apparent that older mice suffered from vaccine-induced immune pathologies, including failure to contain viral replication, augmented clinical disease and associated symptoms, and increased inflammatory response and eosinophilic influx (84, 85). in this respect, there is an overlap between the immunopathologic responses connected with coronavirus this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. m. kyriakopoulos et al. 10 disease and vaccination, and the role of t helper (th) 17 cells in immune augmentation and eosinophilic lung immunopathology; host th17 polarized inflammatory reactions portray an important role in the pathophysiology of covid-19 pneumonia and edema (86, 87). eosinophilic pathology, indicating increased pathogenesis and disease severity in the elderly, has been attributed to the nucleocapsid (n) protein, despite the incorporation of multiple sarscov-1 antigens in the div (82, 84). this is on grounds that the n protein is a strong modulator of innate immunity, also acting as an interferon antagonist, and therefore, it has the capability to induce inflammation with subsequent immune pathology in situations of heterologous viral challenge or in immune senescence, where patients fail to mount effective immune responses against the disease (84, 88). the route of transmission is important to be established for sars cov2. as seen with other important infectious diseases of a) air borne transmission such as tuberculosis (89), b) orofecal transmission such as hev (90) and c) blood transmission such as hbv and hepatitis d virus (91), even if efficient vaccination is established, understanding of sses is still important. recent research data on the immune receptors used by coronaviruses, which reflect their ability to propagate in the human population, imply that complex immune reactions are responsible for a cell to cell transmission. in addition to ace-ii receptor, as is the case with sarscov, mers-cov (92) and possibly for sars-cov-2 (92, 93), viruses use complex receptor recognition systems common to immunopathology damage mechanisms in coronavirusinfected individuals, which clearly define the clinical outcome (94). therefore, application of vaccines that may interfere with antibody-mediated infection by coronaviruses (95) without true epidemiologic containment of coronaviruses, to restrict genetic adaptation events and inevitably producing an sse, may be a miscellaneous attempt. however, synergy of sse prevention measures with proper vaccination can provide a robust attempt for disease containment. 5. limitations this study aimed to perform a literature review. although effort was made to decrease the risk of bias of results via double-blind screening of literature and employment of multiple electronic search engines, bias cannot be eliminated due to incomplete retrieval of identified research and biased estimations of included literature conclusions and methods used. outcome of the study may also contain biased estimations originating from wrong interpretation of super spreading individuals in literature reviewed for sars, mers, and covid-19 outbreaks. although the importance of sses in covid-19 was recognized by this study, more data from future accumulated epidemiology studies are needed to justify these findings. 6. conclusion taken all together, management of sses is mandatory to yield efficient control over sars-cov-2. this is achievable through early diagnosis of pre/asymptomatic infected individuals within potential super spreading groups. prevention of outbreaks is more essential, especially due to the lack of efficient vaccination and therapeutic protocols, which necessitates efficient monitoring, as sars-cov-2 virus follows complex infectious patterns. the sars-cov-2 epidemiological models that do not take sses into consideration seem to lead to confusing results with high uncertainty. sars-cov2 causes prolonged "pandemics" through complex adaptation routes. currently, in addition to the high technology utilized for diagnosis, clinical observation is indispensable to deeply comprehend sses and prohibit further outspread of covid-19. reference laboratories with efficient and accredited molecular and serological diagnosis must be inter-linked between countries. all these parameters could contribute to avoiding a second blind unjustified response that characterized the first covid-19 pandemic spread. understanding the epidemiology of covid-19 through sses could be preventive for future epidemics. a systematic meta-analysis research methodology, when covid-19 epidemiology data accumulate further, would be advisable to confirm the conclusions of this study. 7. declarations 7.1. ethics approval and consent to participate this study did not involve the participation of any humans or animals as it was based only on literature research. 7.2. consent for publication all authors agree to publish this manuscript. 7.3. availability of data and materials all data used for this manuscript are available upon request 7.4. competing interests all authors declare that they have no competing interests. 7.5. funding no funding or grant was received for this study. 7.6. acknowledgements we thank our families for providing moral assistance to accomplish this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e74 7.7. author contribution ak inspired the conception and drafted the initial manuscript. jk revised substantially the manuscript, intellectual content and provided disclosed data for hbv investigation. ak and jk made the primary double-blind search. ap, jk, ak, mn, and ng, made all other searches. ap contributed to the immunology aspect of manuscript. ap and ng aided in the clinical part and preparing the final version of the manuscript. md contributed to bibliographical search and revision of the manuscript. all authors contributed to the english editing of the manuscript. âăč 7.8. abbreviations sars: severe acute respiratory syndrome. sars-cov-2: severe acute respiratory syndrome coronavirus -2. sses: super spread events. covid-19: coronavirus disease 2019. sads: swine acute diarrhea syndrome. ro: basic reproduction number. iqr: interquartile range. mers-cov: middle east respiratory syndrome coronavirus. hiv: human immunodeficiency virus hbv: (human) hepatitis b virus hcv: (human) hepatitis c virus ade: antigen dependent enhancement div: double inactivated virus th: t helper (cell) rt-qpcr: reverse transcriptase 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2009;15(suppl 8):29–33. 98. stein ra. super-spreaders in infectious diseases. international journal of infectious diseases. 2011;15(8):e510-e3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e3 or i g i n a l re s e a rc h characteristics of s100b and neuron specific enolase in differentiating acute vertigo cases with central cause; a diagnostic accuracy study javad mozafari1, hassan motamed1, kambiz masoumi2∗, mohammad ghasem hanafi3, mohammad ali fahimi1, zahra derakhshani1, farzaneh ehyaie4 1. department of emergency medicine, golestan general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 2. department of emergency medicine, imam khomeini general hospital, ahvaz jundishapur university of medical sciences, ahvaz, iran. 3. department of radiology, ahvaz jundishapur university of medical sciences, ahvaz, iran. 4. student research committee, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: october 2019; accepted: december 2019; published online: 28 january 2020 abstract: introduction: differentiating central vertigo from peripheral ones poses a challenge to specialists. the present study aimed to examine the potential screening value of s100b and neuron-specific enolase (nse) in this regard. methods: this prospective cross-sectional study recruited adult acute vertigo patients with suspected central causes visiting the emergency department (ed) in the first six hours since the onset of symptoms. the screening performance characteristics of s100b and nse biomarkers in differentiating central vertigo cases were measured considering brain magnetic resonance imaging (mri) as the reference test. results: 85 cases who met the criteria were enrolled to the study (82.3% female). the mri of 21 (24.7%) cases had abnormal findings. the two groups were the same in terms of age, sex, and vital signs. patients with abnormal brain mri had significantly higher levels of s100b (p < 0.001) and nse (p < 0.001). s100b and nse had area under the receiver operating characteristic (roc) curve of 90.3 (95% ci: 80.7 – 99.8) and 96.9 (95% ci: 93.7 – 100.0) in differentiating the central causes of acute vertigo, respectively. at the cut-off point of above 119.68 pg/l, s100b had sensitivity of 90.00% (95% ci: 78.83 – 95.86) and specificity of 92.00% (95% ci: 72.49 – 98.60). the sensitivity and specificity of nse at the cut-off point of above 18.12 ng/ml were 100.00% (95% ci: 93.14 – 100.00) and 89.47% (95% ci: 65.46 – 98.15), respectively. conclusion: the serum levels of s100b and nse were significantly higher in patients with central vertigo, and could therefore be considered as accurate tools in screening acute vertigo cases with central causes in ed. keywords: vestibular neuronitis; biomarkers; s100b protein, human; phosphopyruvate hydratase; vertigo cite this article as: mozafari j, motamed h, masoumi k, hanafi m g, fahimi m a, derakhshani z, ehyaie f. characteristics of s100b and neuron specific enolase in differentiating acute vertigo cases with central cause; a diagnostic accuracy study. arch acad emerg med. 2020; 8(1): e3. 1. introduction vertigo is a common cause of visits to the emergency department (ed), with a prevalence of 40% in those aged above 40 years (1). given its numerous causes, differentiating central vertigo from peripheral ones poses a challenge to specialists (2). central causes and brain vascular accidents as∗corresponding author: kambiz masoumi; department of emergency medicine, imam khomeini general hospital, ahvaz, iran. email: emdajums@yahoo.com, tel: +98613311 sociated with vertigo are life-threatening and it is vital to find a quick and accessible method for diagnosing central vertigo and posterior cerebral circulation stroke in the ed (3). since the vertebra-basilar circulation supplies important structures such as the brain stem (4), cerebellum, and ventricular and inner ear cochlear structures, acute isolated vertigo may be caused by lack of circulation or stroke in the midbrain (5). a rapid and timely diagnosis of brain ischemia as an emergency cause of vertigo can accelerate therapeutic measures and improve prognosis (6). so far, brain magnetic resonance imaging (mri) has been the best diagnostic method for diagnosing the cause of vague vertigo (7). yet, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. mozafari et al. 2 mri cannot be used for all patients with unclear diagnosis as it is not always accessible and is costly (8). neuron-specific enolase (nse) is a candidate biomarker for central nervous system (cns) damage that passes the bloodbrain barrier (bbb) (9). its neuropath logical levels occur in head trauma accidents or neurological diseases. the normal level of nse can reliably rule out major cns pathologies (10). the main advantage of using nse is that its increased serum or cerebrospinal fluid (csf) concentration can be a sensitive tool for determining cns damage at a molecular level before gross changes emerge. an increase in nse level has been reported before any detectable changes in intracranial pressure, neuroimaging, and neurological examination findings (11, 12). another biomarker of cns damage proposed in the last decade as a peripheral marker of bbb permeability is the calcium-binding protein s100b (13, 14). few studies have measured it in patients complaining of acute vertigo presenting to ed in order to differentiate peripheral vertigo from that caused by posterior circulation stroke (15). serum biomarkers may be effective in determining the need for imaging. the present study aimed to examine the potential screening values of s100b and nse in differentiating true vertigo cases with central causes in the ed. 2. methods 2.1. study design and setting this prospective cross-sectional study recruited adult acute vertigo patients with suspected central causes visiting the ed of golestan hospital, ahvaz, iran from 2017 to 2018, within the first six hours since the onset of symptoms. the declaration of helsinki for research involving human subjects was considered and the ethics committee of ahvaz jundishapur university of medical sciences (ir.ajums.rec.1395.529 and ir.ajums.rec.1396.1033) approved the study protocol. all patients provided written informed consent before entering the study. 2.2. participants patients above 18 years old, with chief complaint of acute vertigo, negative history of vertigo or idiopathic cranial or auditory system pathologies that are classified as central vertigo, and patients without any persistent neurological deficits like weakness or unsteadiness were included. patients not willing to participate were excluded. history of head trauma, disorders on the electrocardiogram (ecg) such as conductive disorders, dysrhythmia, or cardiac ischemia, other neurological exams besides vertigo during examination, visiting later than six hours after the onset of vertigo, having intracranial pathologies in previous radiological examination (e.g. space-occupying masses or previous surgery), contraindication for performing brain mri, diseases such as pulmonary squamous-cell carcinoma (scc), neuroblastoma, melanoma, seminoma, merkel cell carcinoma, tumors, carcinoids, teratoma, malignant pheochromocytoma, guillain– barre syndrome, and creutzfeldt-jakob disease were also among the exclusion criteria. 2.3. study protocol data were gathered from all eligible patients, initial examinations were performed, and ecgs were obtained. soon after initial stabilization, in addition to obtaining regular venous blood samples, a venous blood sample was taken by the ed nurse (trained research assistant) specifically for s100b and nse biomarkers, and the time of sampling was recorded. then, patients were referred to the imaging department for brain mri. blood samples (10 ml) were taken in gel tubes and rested for 30 minutes to clot. the samples were then centrifuged for 10 minutes at 800 to 1000 rpm in the ed laboratory. serum samples were diluted with 1 ml of distilled water and then transferred to test tubes. the preliminary sample was sent to the laboratory for measuring the biomarkers. prior to the final analysis, the samples were maintained at -20 ◦c; they were assayed separately using electrochemiluminescence method. furthermore, all laboratory personnel were blinded to patient data and imaging findings of the two groups. preliminary brain diffusion-weighted mri (dwi) of all patients was separately ordered by an emergency medicine specialist and performed using a single mri machine and interpreted by a neurologist and a radiologist, both blinded to the biomarker results. serum samples were taken within a maximum of six hours after the onset of vertigo. finally, patients were divided into two groups of positive and negative mri findings, and the levels of biomarkers were compared across the two groups. 2.4. statistical analysis all data were analyzed using spss, described using mean and standard deviation (sd) for quantitative, and frequency and percentage for qualitative variables. t-test or mann whitney u test as well as chi-squared test were used for analyzing the data. area under the receiver operating characteristic (roc) curve was calculated in order to determine the predictive value of s100b and nse and the optimal cut-off point of s100b and nse for distinguishing central vertigo based on the best sensitivity and specificity. all results are reported with 95% confidence interval (ci) and p-value of <0.05 was considered significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e3 figure 1: stard flowchart diagram. table 1: comparing the baseline characteristics of patients with positive and negative brain magnetic resonance imaging (mri) findings variables brain mri findings p value positive (n=21) negative(n=64) gender (female) 10 (47.6) 60 (93.7) 0.073 age (years) 49.63 ± 14.74 53.06 ± 16.45 0.398 vital signs sbp (mmhg) 141.12 ± 17.03 138.48 ± 21.91 0.616 dbp (mmhg) 84.09 ± 10.98 77.07 ± 12.17 0.021 rr (/minute) 17.05 ± 2.04 16.80 ± 1.34 0.383 pr (/minute) 79.00 ± 5.70 80.53 ± 5.88 0.300 temperature (c) 36.50 ± 0.321 36.46 ± 0.32 0.603 spo2 (%) 98.08 ± 0.97 97.91 ± 0.93 0.484 biomarker level s100b (pg/ml) 217.13 ± 119.28 77.39 ± 31.67 <0.001 nse (ng/ml) 30.90 ± 7.34 10.92 ± 6.34 <0.001 data are presented as mean ± standard deviation or number (%). sbp: systolic blood pressure; dbp: diastolic blood pressure; rr: respiratory rate; pr: pulse rate; spo2 : peripheral capillary oxygen saturation; nse: neuron specific enolase. 3. results 3.1. baseline characteristics of studied patients 130 patients with acute vertigo and possible central causes were evaluated and finally 85 cases who met the criteria were enrolled in the study (82.3% female; figure 1). the mri of 64 (75.3%) cases was normal and the other 21 patients had chronic ischemic changes. mean age of the patients was 53.06âś16.45 years in the normal mri group and 49.63 ± 14.74 years in the abnormal group. baseline characteristics of patients in both groups are given in table 1. the two groups did not differ in terms of age, sex, and vital signs. patients with abnormal brain mri findings had significantly higher levels of s100b (p < 0.001) and nse (p < 0.001). 3.2. screening value of studied biomarkers table 2 summarizes the screening performance characteristics of s100b and nse biomarkers in differentiating the centhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. mozafari et al. 4 table 2: screening performance characteristics of s100b and neuron specific enolase (nse) biomarkers in differentiating acute vertigo cases with central cause characteristics s100b nse true positive 54 66 true negative 23 17 false positive 2 2 false negative 6 0 sensitivity 90.00 (78.83 – 95.86) 100.00 (93.14 – 100.00) specificity 92.00 (72.49 – 98.60) 89.47 (65.46 – 98.15) positive predictive value 96.42 (86.61 – 99.37) 97.05 (88.83 – 99.48) negative predictive value 79.31 (59.73 – 91.29) 100.00 (77.07 – 100.00) positive likelihood ratio 27.00 (6.91 -105.39) 33.00 (8.41 – 129.34) negative likelihood ratio 0.26 (0.12 – 0.54) 0.00 (0.00 – nan) total accuracy 90.3 (80.7 – 99.8) 96.9 (93.7 – 100.0) data are presented with 95% confidence interval (ci). nan: the calculation cannot be performed because the values entered include one or more instances of zero. figure 2: the area under the receiver operating characteristic (roc) curve of s100b and neuron specific enolase (nse) biomarkers in differentiating acute vertigo cases with central cause. tral causes of acute vertigo. s100b had the area under the roc curve of 90.3 (95% ci: 80.7 – 99.8) for differentiating the causes of acute vertigo (figure 2), and at the cut-off point of above 119.68 pg/l, had sensitivity of 90.00% and specificity of 92.00%, in detecting cases with abnormal mri findings (central cause of vertigo). in addition, the nse biomarker in patients with acute vertigo had the area under the roc curve of 96.9 (95% ci: 93.7 – 100.0; figure 2), and at a cut-off point of above 18.12 ng/ml, had sensitivity of 100.00% and specificity of 89.47%, indicating the central nature of vertigo. 3.3. discussion our findings revealed that s100b and nse have acceptable screening performance characteristics in differentiating acute vertigo cases with central causes. the cause of vertigo may be central (brainstem, cerebellum, or brain involvement) or peripheral (vestibule-cochlear nerve or inner ear labyrinth), systemic (cardiac or metabolic diseases) or psychological (e.g. anxiety). central vertigo may be dangerous and even lead to mortality. yet, it is often difficult to diagnose the cause of vertigo, and only mri imaging has so far been used as the gold standard for diagnosing these cases (16). kartal et al. examined the serum level of s100b in 82 acute vertigo patients within six hours since the emergence of symptoms and reported a sensitivity of 83.9% and specificity of 51% for diagnosing the central cause of vertigo in cases of serum concentration of above 30 pg/ml (15). our results showed that serum level of s100b and nse biomarkers were significantly higher in patients with abnormal mri findings. considering the high sensitivity and specificity at the cut-off point of 19.2 ng/ml, it seems that nse is more valuable than s100b in differentiating peripheral and central causes of vertigo. in the study by bharosay et al., nse level was less than 25 ng/ml in the control group (n=101) and above 25 ng/ml in patients with ischemic stroke (n=70)(17). moreover, in a study by bandhyopadhyay et al. on 79 patients with head trauma and gcs<13, blood samples were taken in the first 3.8 hours on average; seven patients with poor outcome and gcs of <5 had the nse level of 46.4 ± 12.7 ng/ml, and patients with good outcome had the nse level of 19.5 ± 1.4 ng/ml. in cases of serum concentration of above 21.2 ng/ml, nse had the sensitivity of 86% and specificity of 74% in predicting poor outcome (18). fridriksson et al. studied patients with head trauma, and reported that the serum level of nse was higher in 22 patients with abnormal head computed tomography (ct) scan (26.7 ± 21.4 ng/ml) compared to 28 patients with normal ct (17.7 ± 7.8 ng/ml); serum concentration above 15.3 ng/ml had sensitivity of 77% and specificity of 52% in predicting the presence of abnormal brain ct finding (18). although patients with head trauma and reduced level this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e3 of consciousness were excluded in our study, positive mri findings may be indicative of neurological damage, probably consistent with the probability of abnormal ct in the reviewed studies. measuring this biomarker is not costly, it can quickly help diagnose patients suspected of central vertigo in ed, it can reduce hospital stay and costs, and it is easily accessible everywhere compared to mri. therefore, it can be used as a screening test with an acceptable accuracy in cases where differentiating central from peripheral causes is difficult. those with positive test results using this method can be the final candidates for mri. of course, studies on larger samples are required in order to determine a more precise cut-off point. 4. limitation the number of patients with normal mri findings did not match the number of patients with abnormal mri findings. a relatively small sample size was another limitation. 5. conclusion the serum levels of s100b and nse were significantly higher in patients with central vertigo, and could therefore be considered as accurate tools in screening acute vertigo cases with central causes in ed. it is clear that high-risk cases should be confirmed with brain mri as the gold standard tool in this regard. 6. declarations 6.1. acknowledgements the authors wish to acknowledge the support of the deputy of research affairs of the ahvaz jundishapur university of medical sciences as part of zahra derakhshani (research code: u-95108) and farzaneh ehyaie’s (research code: gp96121) theses. 6.2. author contribution j.m and k.m: conceived the original idea, designed the scenarios and collected the data m.gh.h, h.m and m.a.f: carried out the analysis of data, approved the final version that was submitted, revised it, z.d and f.e: drafted the manuscript. all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids javad mozafari: 0000-0002-8903-7138 hassan motamed: 0000-0001-9062-085x kambiz masoumi: 0000-0001-7234-5671 mohammad ghasem hanafi: 0000-0001-9153-3029 6.3. funding/support this study was funded by ahvaz jundishapur university of medical sciences. 6.4. conflict of interest the authors declare that they have no conflict of interest. references 1. wipperman j. dizziness and vertigo. primary care. 2014;41(1):115-31. 2. kerber ka, meurer wj, west bt, fendrick am. dizziness presentations in u.s. emergency departments, 19952004. academic emergency medicine : official journal of the society for academic emergency medicine. 2008;15(8):744-50. 3. peng b. cervical vertigo: historical reviews and advances. world neurosurgery. 2018;109:347-50. 4. hussami a, casulli c, fayard c, caillier-minier m, vion p, minier d. vertebrobasilar stroke secondary to giant-cell arteritis without biological inflammatory syndrome. revue neurologique. 2016;172(3):250-2. 5. dieterich m, glasauer s, brandt t. why acute unilateral vestibular midbrain lesions rarely manifest with rotational vertigo: a clinical and modelling approach to head direction cell function. journal of neurology. 2018;265(5):1184-98. 6. schiff l, hadker n, weiser s, rausch c. a literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury. molecular diagnosis & therapy. 2012;16(2):79-92. 7. bruzzone mg, grisoli m, de simone t, regna-gladin c. neuroradiological features of vertigo. neurological sciences : official journal of the italian neurological society and of the italian society of clinical neurophysiology. 2004;25 suppl 1:s20-3. 8. newman-toker de, della santina cc, blitz am. vertigo and hearing loss. handbook of clinical neurology. 2016;136:905-21. 9. haque a, ray sk, cox a, banik nl. neuron specific enolase: a promising therapeutic target in acute spinal cord injury. metabolic brain disease. 2016;31(3):487-95. 10. samanci y, samanci b, sahin e, altiokka-uzun g, kucukali ci, tuzun e, et al. neuron-specific enolase levels as a marker for possible neuronal damage in idiopathic intracranial hypertension. acta neurologica belgica. 2017;117(3):707-11. 11. liu b, xie z, liu g, gu y, pan s, wang h. elevated neuronspecific enolase and s100 calcium-binding protein b concentrations in cerebrospinal fluid of patients with anti-n-methyl-d-aspartate receptor encephalitis. clinica this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem j. mozafari et al. 6 chimica acta; international journal of clinical chemistry. 2018;480:79-83. 12. olivecrona m, rodling-wahlstrom m, naredi s, koskinen lo. s-100b and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy. journal of neurology, neurosurgery, and psychiatry. 2009;80(11):1241-7. 13. kogel d, peters m, konig hg, hashemi sm, bui nt, arolt v, et al. s100b potently activates p65/c-rel transcriptional complexes in hippocampal neurons: clinical implications for the role of s100b in excitotoxic brain injury. neuroscience. 2004;127(4):913-20. 14. hajdukova l, sobek o, prchalova d, bilkova z, koudelkova m, lukaskova j, et al. biomarkers of brain damage: s100b and nse concentrations in cerebrospinal fluid–a normative study. biomed research international. 2015;2015:379071. 15. kartal ag, yilmaz s, yaka e, pekdemir m, sarisoy ht, cekmen mb, et al. diagnostic value of s100b protein in the differential diagnosis of acute vertigo in the emergency department. academic emergency medicine : official journal of the society for academic emergency medicine. 2014;21(7):736-41. 16. thelin ep, nelson dw, bellander bm. a review of the clinical utility of serum s100b protein levels in the assessment of traumatic brain injury. acta neurochirurgica. 2017;159(2):209-25. 17. dijkhuizen rm. advances in mri-based detection of cerebrovascular changes after experimental traumatic brain injury. translational stroke research. 2011;2(4):52432. 18. bandyopadhyay s, hennes h, gorelick mh, wells rg, walsh-kelly cm. serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. academic emergency medicine : official journal of the society for academic emergency medicine. 2005;12(8):732-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results limitation conclusion declarations references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 7 emergency (2013); 1 (1): 7-10 original research accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures mehrdad esmailian1, ehsan haj zargarbashi1*, babak masoumi1, mehdi karami2 1. department of emergency medicine, isfahan university of medical sciences, isfahan, iran 2. department of radiology, isfahan university of medical sciences, isfahan, iran abstract introduction: restoration of normal anatomic alignment is a key component of the treatment of distal radius fractures (drf). this study aimed to evaluate the accuracy of ultrasonography (us) in determining the adequacy of closed reduction in these fractures. methods: drf patients admitted to the emergency department of al-zahra hospital, isfahan, iran from september 2011 to 2012, were enrolled. after closed reduction, the adequacy was investigated through both us and control plain radiography. then, sensitivity, specificity, positive and negative predicative values of us in confirmation of closed reduction was evaluated. in addition, inter-rater agreement between the two diagnostic tools was analyzed by calculating cohen’s kappa coefficient. results: finally, 154 patients were evaluated (females: 53.9%) with mean age of 40.03±14.7 (range: 22-73). us had sensitivity, specificity, positive and negative predictive value of 99.3% (95%ci: 96.2-99.9), 100.0% (95%ci: 62.9-100.0), 100.0% (95%ci: 97.5-100.0), and 88.9% (95%ci: 51.7-98.1) in confirmation of the adequate reduction, respectively. in addition, inter-rater reliability was 0.94 (95%ci: 0.89-0.99; p<0.0001). conclusion: it seems that us could be considered as a highly sensitive, accurate, easy to use, noninvasive and safe tool for guidance and confirmation of closed reduction in drf. key words: radius fractures; closed fractures; reduction; ultrasonography cite this article as: esmailian m, haj zargarbashi e, masoumi b, karami m. accuracy of ultrasonography in confirmation of adequate reduction of distal radius fractures. emergency. 2013;1(1):7-10. introduction:1 istal radius fractures (drf) is one of the most common cause of emergency department visits, comprising approximately one-sixth of fracture cases (1, 2). except for trauma, pathological fractures due to osteoporosis, especially in elderly patients, is also one of the causes for this type of fracture (3, 4). depending on the type of fracture, management is different, but generally it needs closed reduction, casting and future follow-up (5). restoration of normal or nearly normal anatomic alignment is acknowledged as a key component of the treatment of drf. at present, plain radiography is used as a control standard for reducing drf (6). conditions such as inflammation of surrounding soft tissues prevent the physician from gaining adequate information about the reduction procedure carried out, which in turn can lead to requesting repeated radiographs. it can increase the need for sedation, unnecessary exposure to x-rays, and infliction of higher expenses (7). recently, the use of ultrasonography (us) instead of plain radiography has been under consideration as a practical monitoring tool of *corresponding author: ehsan haj zargarbashi; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: +989136470851; fax:+983117923445 email: dr.ehsanzargarbashi@yahoo.com received: 12 october 2013; accepted: 16 november 2013 closed reductions in extra-articular drf (1, 2, 6). accordingly, the present study was aimed to evaluate the accuracy of bedside us for determining the adequacy of drf reduction compared with standard plain radiography. methods: study design and setting this cross sectional study has been performed from september 2011 to september 2012 in the emergency department of al-zahra hospital, isfahan, iran. the study protocol was approved by isfahan university of medical sciences institutional review board and registered in www.clinicaltrial.gov by registration code: nct01823692. an informed consent was fulfilled by all enrolled patients. based on the study protocol, us and radiographic findings were compared in the same group of patients. participants patients undergoing sono-guided manipulation and reduction were enrolled over a twelve-month period, representing a convenience sample. eligible patients were prospectively recruited based on the inclusion criteria as age>18 and diagnosis of drf based on plain radiography. in addition, the exclusion criteria consisted of the following: open fractures, fractures with more than 20° angulation, intra-articular involvement, comminuted fractures with neurovascular compromise, d mailto:dr.ehsanzargarbashi@yahoo.com http://www.clinicaltrial.gov/ this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 8 esmailian et al patients requiring surgery due to other causes, need to intensive care, and patients’ refusal to participate in the study. intervention after registration of demographic data, the patients underwent manipulation and reduction by one emergency medicine specialist under bier block regional anesthesia or procedural sedation-analgesia. this physician passed a comprehensive training course regarding to sono-guided reduction, and determining the sufficiency of reduction based on us findings. us was performed in a long axis in both anterior-posterior and lateral views (figures 1 and 2). when the distal and proximal cortices aligned into a straight line (less than 3 mm difference), the reduction was defined as successful. follow-up plain radiographs were also obtained in the anterior-posterior and lateral views (gold standard) and reviewed by one blinded radiologist. if plain radiographs had the following criteria, the reduction was considered successful: 1) normal radial inclination of 15-25°; 2) radial height at least 5 mm or higher; 3) volar/palmar tilt -10° to +20° (8) (figure 3). finally, proper fixation was applied. distal radius was defined as a distance less than 3 cm from the radio-carpal joint (9). statistical analysis following a descriptive analysis, the sensitivity, specificity, and positive and negative predicative values were calculated. in addition, cohen’s kappa coefficient was used to evaluate inter-rater reliability between us and radiographic findings. kappa index values <0.2, 0.210.4, 0.41-0.6, 0.61-0.8 and >0.8 were considered weak, rather weak, moderate, good, and excellent, respectively. data were analyzed by spss version 20.0 and statistical significance was defined at p<0.05. results: of the 180 patients initially enrolled in the study, 26 were excluded in the final analysis (10 with open fractures, six angulation>20°, five intra-articular involvement and five neurovascular compromise). finally, 154 patients participated in this study (53.9% female; ultrasonographic views of distal radius fracture a b a figure 1: anterior-posterior view: (a) before reduction; (b) after reduction.  figure 2: lateral view: (a) before reduction; (b) after reduction.  figure 3: conventional radiographic parameters. from left to right: radial inclination; radial height; volar tilt.  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 9 emergency (2013); 1 (1): 7-10 55.2% right hand drf) with mean age of 40.03±14.7 (range: 22-73). table 1 present the baseline characteristics of these patients. based on us and radiographic findings successful reduction was confirmed in 145 (94.2%) and 146 (94.8%) cases, respectively. us had sensitivity, specificity, positive and negative predictive value of 99.3%, 100.0%100.0%, and 88.9% in confirmation of successful reduction, respectively (table 2). in addition, inter-rater agreement of reduction success between the two assessment methods was 99.35%. in addition, inter-rater reliability based on cohen’s kappa coefficient was 0.94 (95% ci: 0.89-0.99; p<0.0001). discussion: the results of the present study showed a high rate of similarity between us and radiographic findings in confirmation of adequate reduction. it seems that a sensitivity of 99.3% and a specificity of 100% make us a reliable tool for evaluation of successful reduction. sonoguided reduction is an accurate, simple, and safe technique that provides the considerable advantage of realtime observation. in addition us should decrease the number of reduction attempts and consequently fewer traumas to the surrounding soft tissues (8). previous studies have been reported the sensitivity and specificity of us in confirming the adequacy of reduction between 94%-96% and 56%-97%, respectively (2, 10). considering the limitation of us in observation of the articular surface, because of their deep-seated position and blocked by carpal component, we excluded all patients with intra-articular fractures. this fact could explain the high sensitivity and specificity of this study. multiple studies have been declared the successful utility of sono-guided reduction for different type of fractures. ang et al. stated that us guidance is effective and recommended it for routine use in the reduction of drf (8). eckert et al confirm that ultrasound is an applicable and safe alternative tool to x-rays in non-displaced forearm fractures (10). chern et al. depicted that all parameters measured on the us and radiographic findings showed remarkable restoration of anatomic alignment after reduction, and all indicators were the same on the two types of images (11). some inherent characteristics of us such as: inability to bone penetration, observation of articular surface, and measurement of conventional radiographic parameters); unlike successful rate in different age (12, 13); quality and quantity of the training courses; and operator dependency; are among limitations in the widespread use of us for guidance and confirmation of closed fracture reduction in ed. therefore, our result may not be applicable to other age groups, or other fracture sites. in addition, although we standardized the initial training for the physicians, our study size was too small to make meaningful subgroup analysis based on level of training or prior us experience. finally, while us has some limitations that prevent it from completely replacing conventional radiography, it can facilitate the reduction and prevent repeated reduction attempts. conclusion: it seems that us could be considered as a highly sensitive, accurate, easy to use, noninvasive and safe tool for guidance and confirming of closed reduction in drf. acknowledgments: we thank the emergency department staff of al-zahra hospital for helping us in conducting this study. conflict of interest: none funding support: this study was supported financially by isfahan university of medical sciences, isfahan, iran. authors’ contributions: all authors met all four recommended criteria of international committee of medical journal editors for authorship contribution. table 1: patients’ baseline characteristics  variables number (%) age (year) 22-35 80 (52.0) 36-50 33 (21.4) 51-65 27 (17.5) >66 14 (9.1) gender male 71 (46.1) female 83 (53.9) side of fracture left 64 (41.6) right 85 (55.2) both hands 5 (3.2) anesthesia procedural sedation 141 (91.6) bier block 13 (8.4) table 2: accuracy of ultrasonography in confirmation of adequate reduction compare to radiography  screening characteristics value (%) 95% ci sensitivity 99.3 96.2-99.9 specificity 100.0 62.9-100.0 positive predictive value 100.0 97.5-100.0 negative predictive value 88.9 51.7-98.1 positive likelihood ratio ---- negative likelihood ratio 0.01 0.00-0.05 ci: confidence interval this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 10 esmailian et al references: 1. chen l, kim y, moore cl. diagnosis and guided reduction of forearm fractures in children using bedside ultrasound. pediatr emerg care. 2007;23(8):528-31. 2. chinnock b, khaletskiy a, kuo k, hendey gw. ultrasoundguided reduction of distal radius fractures. j emerg med. 2011;40(3):308-12. 3. adams bd. effects of radial deformity on distal radioulnar joint mechanics. j hand surg. 1993;18 (3):492-8. 4. cuenca j, martinez a, herrera a, domingo j. the incidence of distal forearm fractures in zaragoza (spain). chirurgie de la main. 2003;22(4):211-5. 5. krackhardt t, dilger j, flesch i, höntzsch d, eingartner c, weise k. fractures of the distal tibia treated with closed reduction and minimally invasive plating. arch orthop trauma surg. 2005;125(2):87-94. 6. ackermann o, liedgens p, eckert k, et al. ultrasound diagnosis of juvenile forearm fractures. j med ultrason. 2010;37(3):123-7. 7. durston w, swartzentruber r. ultrasound guided reduction of pediatric forearm fractures in the ed. am j emerg med. 2000;18(1):72-7. 8. ang s-h, lee s-w, lam k-y. ultrasound-guided reduction of distal radius fractures. am j emerg med. 2010;28(9):1002-8. 9. mallmin h, ljunghall s. incidence of colles' fracture in uppsala: a prospective study of a quarter-million population. acta orthop. 1992;63(2):213-5. 10. eckert k, ackermann o, schweiger b, radeloff e, liedgens p. sonographic diagnosis of metaphyseal forearm fractures in children: a safe and applicable alternative to standard x-rays. pediatr emerg care. 2012;28(9):851-4. 11. chern t-c, jou i-m, lai k-a, yang c-y, yeh s-h, cheng s-c. sonography for monitoring closed reduction of displaced extra-articular distal radial fractures. j bone joint surg. 2002;84(2):194-203. 12. chang h, tay s, chan b, low c. conservative treatment of redisplayed collies' fractures in elderly patients older than 60 years old-anatomical and functional outcome. hand surg. 2001;6(02):137-44. 13. anzarut a, johnson ja, rowe bh, lambert rg, blitz s, majumdar sr. radiologic and patient-reported functional outcomes in an elderly cohort with conservatively treated distal radius fractures. j hand surg. 2004;29(6):1121-7. archives of academic emergency medicine. 2019; 7 (1): e21 or i g i n a l re s e a rc h quebec decision rule in determining the need for radiography in reduction of shoulder dislocation; a diagnostic accuracy study ehsan bolvardi1, behnaz alizadeh1, mahdi foroughian1, bita abbasi2, seyed reza habibzadeh1, reza akhavan1∗ 1. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. department of radiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: november 2018; accepted: december 2018; published online: 25 february 2019 abstract: introduction: the quebec decision rule (qdr) has been developed for deciding on the necessity of radiography for patients with shoulder dislocation. this study aimed to investigate the diagnostic value of qdr in this regard. methods: this diagnostic accuracy study was conducted on patients with shoulder dislocation visiting the emergency department. after filling out the qdr-based checklist for all patients, they underwent radiography and the obtained radiography results were compared to qdr-based clinical diagnostic findings. results: 143 patients with the mean age of 32.1 ± 12 years were evaluated (88.8% males). sensitivity, specificity, and positive and negative predictive values of qdr were 50%, 58.2%, 3.3%, and 97.6%, respectively. the sensitivity and specificity were 100% and 50% in patients > 40 years old, and 33.3% and 59.8% in those < 40 years old. these indices were 33.3% and 60.4%, respectively, in the male sex and 100% and 40% in the female sex. conclusion: quebec decision rule holds promise to diagnose concomitant fractures in patients over the age of 40 with 100% sensitivity, thereby reducing the number of radiographies by 50% without causing diagnostic errors. in contrast, this criterion proved inefficient in patients younger than 40. keywords: quebec; shoulder dislocation; decision support techniques; diagnostic imaging; radiography cite this article as: bolvardi e, alizadeh b, foroughian m, abbasi b, habibzadeh s r, akhavan r. quebec decision rule in determining the need for radiography in reduction of shoulder dislocation; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e21. 1. introduction shoulder dislocation is the most common type of joint dislocation in humans with the prevalence of 17-23 cases per each 100,000 population (1-3). closed-reduction is usually a successful initial treatment for anterior shoulder dislocation (4). in the majority of cases, preand post-reduction radiography are advocated to confirm dislocation and ensure the complete reduction and evaluation for fractures (5). current studies have questioned the need for preand postreduction radiographs in shoulder dislocation (5-7). according to researchers’ findings, radiographs are needed to confirm the location of the reduced joint in dislocations with an associated fracture or when the physician is uncertain ∗corresponding author: reza akhavan; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: 05138525312; email: akhavanr@mums.ac.ir (8). the quebec shoulder dislocation (qsd) rule is a clinical decision-making guideline, designed by a group of canadian researchers, to guide physicians about the indications of radiography in patients with a shoulder dislocation. this guideline advocates the use of pre-reduction radiography in adult patients younger than 40 years if the mechanism of injury involves a motor vehicle collision, a fall from standing height, or a sports injury. in young people, these guidelines have a sensitivity of 100% and a negative predictive value of 99.2% in diagnosis of clinically important fractures and can reduce the number of pre-reduction radiographies by 27.9% (9). nevertheless, all of these findings were not confirmed by all subsequent studies. although these findings indicate that preand post-reduction radiography are not needed for all patients with shoulder dislocation, there is still no standard, reliable, generally applicable, and broadly accepted technique. since the preand post-reduction radiography processes are significantly time-consuming and expose the patients to harmful radiation and impose a huge financial this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bolvardi et al. 2 burden on them and the healthcare system, this study intended to investigate the diagnostic value of this guideline in patients with shoulder dislocation, visiting emergency department. 2. methods 2.1. study design and setting this cross-sectional (diagnostic accuracy) study was conducted on patients with shoulder dislocation visiting imam reza and shahid hasheminejad hospitals of mashhad, iran, between december 2016 and december 2017. this project was approved by the ethics committee of mashhad university of medical sciences under the code ir.mums.fm.rec.1394.599. researches adhered to principles of helsinki declaration and confidentiality of patients’ information during the study period. 2.2. participants all patients who presented to the emergency departments of the mentioned hospitals during the study period were enrolled without any gender limitation using the convenience sampling technique. patients less than 18 years old, as well as patients with neural or vascular injuries in the affected organ were excluded. 2.3. data gathering a checklist containing the baseline characteristics of the patients as well as qdr variables was designed for data gathering. after obtaining informed consent from the participants, the qdr-based designed checklist was completed for all participants. then standard digital radiography (ap-lateral-y view) was performed. if the radiographs confirmed dislocation, shoulder reduction would be carried out after procedural sedation and analgesia based on the existing department protocol (fentanyl 1micro/kg + propofol 1mg/kg). finally, results of qdr criteria regarding the need for imaging were compared to radiographs and its sensitivity, specificity, and negative and positive predictive values were calculated. data gathering and examinations were performed by emergency medicine physicians. all radiographs were interpreted by two emergency medicine physicians and a radiologist was consulted whenever there were disagreements or diagnostic uncertainties. according to qdr, pre-reduction radiography is necessary for adult patients younger than 40 if the injury involves a motor vehicle collision, fight, a fall from standing height, or sports injury. qdr also recommends radiography for patients under 40 with and without ecchymosis who have their first-time shoulder dislocation (10). 2.4. statistical analysis the required sample size estimation was 140 patients based on the confidence interval of 95% and accuracy of 12% (10). the controlled data was fed into spss 12 and analyzed using tables, diagrams, and central and distribution indices. findings were reported using mean ± standard deviation or frequency and percentage. p<0.05 was considered statistically significant. student’s t-test and chi square test were used for comparing the two groups regarding quantitative and qualitative variables, respectively. the diagnostic values including sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were reported with 95% confidence interval. 3. results 3.1. baseline characteristics of studied patients 143 patients with the mean age of 32.1 ± 12 (8 – 74) years were studied (88.8% male). the patients’ baseline characteristics, major causes of dislocation, side of dislocation, and pre-reduction radiographic findings are presented in table 1. patients < 40 and > 40 years old were similar regarding the baseline characteristics. patients <40 years old had a significantly higher rate of recurrent dislocation (4.9 ± 6.2 vs 1.5 ± 0.5 times; p < 0.001). 3.2. diagnostic accuracy of qdr according to qdr criteria, there was an indication for prereduction radiography in 60 (42%) patients. two out of four patients (50%) with concomitant fractures had radiography indication based on qdr. the overall screening performance characteristics of qdr based on gender and age are presented in table 2. quebec decision rule has an excellent sensitivity in patients older than 40 years, and also in females (both 100%). the observed positive likelihood ratio (lr+) for qdr criteria was 1.19 and the negative likelihood ratio (lr-) was 0.85 for the whole study population. however, the highest lr+ for this test belonged to patients older than 40 years and females. 4. discussion based on the qdr criteria, pre-reduction radiography was indicated in 42% of the study subjects. the sensitivities and specificities of qdr in diagnosis of concomitant fracture and need for pre-reduction were 50% and 58.2%, respectively. application of qdr can reduce the number of radiographies by 56%. since preand post-reduction radiographies seem unnecessary for all patients with shoulder dislocation, a guideline for indication of radiography is needed in these patients. qdr is among the most important attempts made in this regard (10). based on one study, in young people, qdr guidethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e21 table 1: baseline characteristics of the study population variables age (years) p value < 40 (n=120) > 40 (n=23) gender male 110 (91.7) 17 (73.9) 0.24 female 10(8.3) 6(26.1) type of dislocation anterior 117 (97.5) 23 (100) >0.99 posterior 3 (2.5) 0 (0) side of dislocation right 92 (76.7) 19 (82.6) 0.78 left 28 (23.3) 4 (17.4) mechanism of dislocation motor vehicle collision 13 (10.8) 0 (0) fights 8 (6.7) 0 (0) falling 14 (11.7) 15 (65.2) n/a exercise 16 (13.3) 0 (0) other 69 (57.5) 8 (34.8) clinical signs ecchymosis 3 (2.5) 0 (0) >0.99 none 117 (97.5) 23 (100) pre-reduction x-ray normal 117 (97.5) 22 (95.7) 0.508 fracture 3 (2.5) 1 (4.3) post-reduction x-ray normal 117 (100) 22 (100) n/a abnormal 0 (0) 0 (0) need for imaging (qdr) indicated 48 (40.0) 12 (52.2) 0.357 not indicated 72 (60.0) 11 (47.8) data are presented as frequency (%). qdr: quebec decision rule. table 2: screening performance characteristics of quebec decision rule in patients with shoulder dislocation total > 40 years < 40 years male female sen 50.0(6.7-93.2) 100(2.5-100) 33.3(0.8-90.6) 33.3(0.8-90.6) 100(2.5-100) spec 58.2(49.6-66.6) 50(28.2-71.8) 59.8(50.4-66.8) 60.4(51.3-69.1) 40(16.3-67.7) ppv 3.3(1.3-8.6) 8.3(5.6-12.1) 2(0.4-9.7) 2(0.4-9.3) 10(6.8-30.2) npv 97.6(93.7-99.0) 100(n/a) 97.2(93.9-98.7) 97.4(94.3-98.8) 100(n/a) lr+ 1.19(0.44-3.25) 2(1.31-3.03) 0.83(0.16-4.17) 0.84(0.16-4.24) 1.66(1.10-2.51) lr0.85(0.31-2.30) 0(n/a) 1.11(0.49-2.51) 1.10(0.48-2.48) 0(n/a) data are presented with 95% confidence interval. sen: sensitivity; spec: specificity; ppv: positive predictive value; npv: negative predictive value; lr+: positive likelihood ratio; lr-: negative likelihood ratio. n/a: not applicable. line has a sensitivity of 100% and a negative predictive value of 99.2% in diagnosis of clinically important fractures and can reduce the number of pre-reduction radiographies by 27.9% (10). nevertheless, studies still cannot absolutely confirm or deny its efficiency in evaluation of shoulder dislocation. clinical evidence can lead experienced emergency medicine physicians to diagnosis of anterior shoulder dislocation and eliminate radiographies before reduction (11, 12). it has been reported that although 37% of fractures were observed in post-reduction radiographs, none of the missed cases affected the treatment outcome. accordingly, although shoulder dislocation is likely to be associated with fractures, which may be missed in the initial radiographs because of their small size or joint position, they do not necessitate a different treatment process (13). three important factors that correlated with fracture were age greater than 40 years, no prior dislocation, and injury mechanism. accordingly, shoulder radiography is advocated for cases with a first-time dislocation, traumatic mechanism, and when the physician is uncertain of joint position. this algorithm reduced the number of radiographies by 46% and resulted in significant savings in time in a previous study. on the other hand, no missed fracture or dislocation was observed in cases without shoulder radiography (14). there are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem e. bolvardi et al. 4 some similar studies on the sensitivity and accuracy of qdr criteria. for example, emond et al. (10) investigated the sensitivity and specificity of qdr criteria and found 100% sensitivity and 34.2% specificity, and a negative predictive value of 99.2%. the use of this criterion reduced the use of preand post-reduction radiographies by 27.9% and 81.9%, respectively. abuye et al. (15) also investigated qdr and showed that this algorithm could reduce the number of radiographies by 50%. the researchers concluded that injury mechanism and recurrent dislocation are two important factors to determine whether pre-reduction radiography is needed. these findings are completely consistent with our findings. due to a significant difference in the mechanism of dislocation and the prevalence of associated fracture by age, we investigated the efficiency of qdr in two specific age groups (older and younger than 40). results suggested a higher sensitivity and negative predictive value in patients older than 40 years. ong et al. studied 196 patients under 40 and found that 59% of them were at high risk according to qdr. in total, 12 (6%) fracture cases were observed. accordingly, qdr reached a sensitivity of 42%, a specificity of 40%, and a predictive value of 91% for associated fracture evaluation in such patients. similar to the current study, ong et al. showed inefficiency of qdr criteria in patients under 40 (5). orloski et al. investigated 7,209 patients with dislocation, 465 (6.5%) of which had associated fracture. they found that a small percentage of fractures occurred in the second (0.7%) and third (0.8%) decades of life. the prevalence of fracture in the fourth and fifth decades of life was 2.6% and 4.6%, respectively. this rate increased by at least 19% in the 8th-10th decades of life. not performing pre-reduction radiography for patients in their second and third decades of life may reduce pre-reduction radiography by 40%. according to them, since the risk of fracture is below 1% in the second and third decades of life, the use of routine pre-reduction radiography for patients with shoulder dislocation can be reduced, which is inconsistent with our findings (14). in our study, both lr+ and lrin total population were similar with regard to the ability to differentiate patients who need radiography from those who do not. in other words, there is no difference in using this tool as a "screening" or "definite diagnosis" method for performing radiography before reduction. however, the highest lr+ was observed in females, it seems that it can be used as an acceptable "screening" tool in this gender. 5. limitation in this study, sample size and hospital selection were among the limitations and studies with larger sample size and different hospitals are needed to confirm our results. 6. conclusion qdr holds promise to accurately diagnose fractureassociated shoulder dislocation in patients above 40 years with a sensitivity of 100%. it can also reduce unnecessary radiographies in such patients by 50% without leaving any fracture undetected. 7. appendix 7.1. acknowledgements the research team would like to thank the nursing staff and the emergency medical staff of imam reza (p.b.h) & shahid hasheminejad hospitals of mashhad, who collaborated in the study. 7.2. author contribution study design, literature search, data gathering and analysis were done by eb, ba, mf, ba, rh and ra. manuscript preparation and drafting were done by all authors. final version of the manuscript was accepted by all authors. authors orcids ehsan bolvardi: 0000-0001-6819-9237 mahdi foroughian: 0000-0002-3944-9361 bita abbasi: 0000-0001-9162-2312 seyed reza habibzadeh: 0000-0003-4569-1776 reza akhavan: 0000-0002-2501-3815 7.3. funding/support the study was financially supported by mashhad university of medical sciences, and accepted by deputy of research of mashhad university of medical sciences as an approved proposal receiving the code 940521. 7.4. conflict of interest the authors declare that there are no conflicts of interest regarding the publication of this manuscript. references 1. cunningham nj. techniques for reduction of anteroinferior shoulder dislocation. emergency medicine australasia. 2005;17(5-6):463-71. 2. kesmezacar h. the evaluation and treatment of acute anterior shoulder dislocation. acta orthopaedica et traumatologica turcica. 2005;39:40-7. 3. uehara d, rudzinski j. [injuries to the shoulder complex and humerus. emergency medicine: a comprehensive study guide] 5th ed ed. new york: mcgraw-hill; 2000. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e21 4. wen dy. current concepts in the treatment of anterior shoulder dislocations. the american journal of emergency medicine. 1999;17(4):401-7. 5. ong s, kelly a-m, gunn b. failed validation of the quebec shoulder dislocation rule for young adult patients in an australian emergency department. canadian journal of emergency medicine. 2011;13(3):150-4. 6. emond m, le sage n, lavoie a, rochette l. clinical factors predicting fractures associated with an anterior shoulder dislocation. academic emergency medicine : official journal of the society for academic emergency medicine. 2004;11(8):853-8. 7. mofidi m, ahmadi k. audit on necessity of radiographs in anterior shoulder dislocations. journal of mazandaran university of medical sciences ( jmums). 2008;17(62). 8. hendey gw, kinlaw k. clinically significant abnormalities in postreduction radiographs after anterior shoulder dislocation. annals of emergency medicine. 1996;28(4):399-402. 9. reid s, liu m, ortega h. anterior shoulder dislocations in pediatric patients: are routine prereduction radiographs necessary? pediatric emergency care. 2013;29(1):39-42. 10. emond m, le sage n, lavoie a, moore ljcjoem. refinement of the quebec decision rule for radiography in shoulder dislocation. 2009;11(1):36-43. 11. shuster m, abu-laban rb, boyd j, gauthier c, shepherd l, turner c. prospective evaluation of a guideline for the selective elimination of pre-reduction radiographs in clinically obvious anterior shoulder dislocation. canadian journal of emergency medicine. 2002;4(4):257-62. 12. mofidi m, ahmadi kjjomuoms. audit on necessity of radiographs in anterior shoulder dislocations. 2008;17(62). 13. shuster m, abu-laban rb, boyd j. prereduction radiographs in clinically evident anterior shoulder dislocation. the american journal of emergency medicine. 1999;17(7):653-8. 14. orloski j, eskin b, allegra pc, allegra jr. do all patients with shoulder dislocations need prereduction xrays? the american journal of emergency medicine. 2011;29(6):609-12. 15. ortells abuye n. shoulder dislocations attended in a regional hospital: are all the radiographs ordered necessary. emergencias. 2014;26:121-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e55 rev i ew art i c l e pre-hospital pain management; a systematic review of proposed guidelines mahmoud yousefifard1, shaghayegh askarian-amiri2, arian madani neishaboori2, mostafa sadeghi3, peyman saberian4, alireza baratloo5,6∗ 1. prevention of cardiovascular disease research center, shahid beheshti university of medical sciences, tehran, iran. 2. physiology research center, faculty of medicine, iran university of medical sciences, tehran, iran. 3. department of anesthesiology and critical care, shariati hospital, tehran university of medical sciences, tehran, iran. 4. department of anesthesiology, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. 5. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 6. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. received: august 2019; accepted: september 2019; published online: 6 october 2019 abstract: introduction: a standard guideline concerning pre-hospital pain management is still a matter of discussion. therefore, the current umbrella review is determined to perform a comprehensive search in databases and grey literature and collect and summarize the guidelines and protocols dealing with prehospital pain management. methods: in the present study, all of the available guidelines and protocols concerning pre-hospital pain management were reviewed. presented guidelines are from 2010 up to present, as the majority of guidelines are considered old and become renewed after 10 years. finally, the development quality of each guideline was evaluated using agree ii instrument. results: the search conducted in databases and non-indexed protocols resulted in inclusion of 12 pre-hospital pain management guidelines. the time interval of the guidelines was from 2010 to 2019. four guidelines were designed for pain management in trauma patients and other guidelines were presented for all of the clinical conditions associated with pain. all of the 12 included guidelines presented pain management instructions in adults. pain management in children was reported in 10 guidelines. all of the guidelines persisted on a standard method for pain evaluation. pain management was categorized in three groups; mild, moderate and severe pain. most of the guidelines recommend paracetamol as an optional treatment for management of mild pain in both adults and children. in management of moderate and severe pain, fentanyl and morphine were suggested for both adults and children. in most of the treatment guidelines fentanyl is the optional choice for children. conclusion: the present umbrella review has summarized the current evidence in pre-hospital pain management for the first time via investigation of guidelines and protocols related to the matter. based on the obtained evidence, no guideline is yet presented concerning opioid-free management of moderate and severe pain. the evidence is insufficient for using non opioid medications such as ketamine. keywords: pain management; practice guideline; drug therapy; emergency medical services cite this article as: yousefifard m, askarian-amiri sh, madani neishaboori a, sadeghi m, saberian p, baratloo a. pre-hospital pain management; a systematic review of proposed guidelines. arch acad emerg mede. 2019; 7(1): e55. 1. introduction p ain management has been a priority for prehospital and hospital care, and a variety of guidelines have been adopted accordingly (1). existence of moderate ∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, hasanabad square, tehran, iran. tel: +989122884364; email: arbaratloo@sina.tums.ac.ir, alirezabaratloo@yahoo.com. to severe pain is one of the most important factors, which alternates patients’ conditions and might have a negative impact on their physiological parameters, which could eventually worsen the patient’s prognosis (2, 3). pharmacological treatment choices in prehospital pain management are quite limited, considering that in prehospital care, analgesics should not only be effective and safe, but also not interfere with patients’ transfer (1). based on literature reviews done in recent years and different this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 2 expert panels conducted, several guidelines have been proposed for pain management in prehospital care (4-6). these guidelines suggest different treatment options varying from injectable opioids to intranasal non-opioid treatments. nevertheless, instructions given by these protocols are usually taken from moderate to low quality studies (7), thus, there is no consensus over a single guideline. on the other hand, the majority of these guidelines only refer to a single disease or complication. in these instructions a broad range of analgesic drugs are proposed. some of the guidelines suggest using multiple drugs instead of a single medication; and some others suggest using opioids in lower doses (4-8). clearly, there is not a consensus over establishing standard instructions on pre-hospital pain control. hence, the present systematic review aims to collect and summarize pre-hospital pain management guidelines and instructions by conducting an extensive research in databases. 2. method 2.1. study design and search strategy the current study is an umbrella review, which investigates the guidelines and protocols for pre-hospital pain management. the researchers conducted a comprehensive search in electronic databases. appropriate keywords were defined to accomplish the study’s objectives. for this purpose, "prehospital emergencies" and "analgesia" related words were obtained with advice of an experienced researcher in the field. additionally, mesh and emtree word trees were investigated. the attained keywords were properly combined, and standard tags were adapted for each database. subsequently, a comprehensive search was conducted in electronic databases including: medline, embase, trip medical database and scopus through march 2019. search strategy in medline database is presented in panel 1. in addition to systematic search, manual search was also performed in google search engine, google scholar and references of relevant articles. 2.2. selection criteria in the present study, guidelines and protocols concerning pre-hospital pain management, published in peer-review journals or released in valid organizations’ websites, were included. reviews being narrative, lack of a report on the complete process of the guideline’s extraction, and lack of a report on the systematic review’s process were considered as exclusion criteria. 2.3. data collection the data collected from databases were saved in endnote. two independent researchers studied the records and screened titles and abstracts of relevant guidelines. after studying the full text of these guidelines, data were filed in a checklist created in microsoft excel. obtained results were perused by the two researchers with the presence of a third researcher. any disagreement was discussed and resolved. recorded data in the checklist consisted of name of the guideline, year of publication, studied medications, quality control and patients’ conditions (trauma, etc.). in cases of non-extractable data in the articles, their authors were contacted. if the author did not respond to the first email, a reminder was sent. in case of no response, second reminder email was sent within two weeks. granted that still no response was received, the other authors were contacted via social media such as researchgate and linkedin to attain required data. 2.4. quality assessment of the articles quality assessment of the articles was performed using agree ii guideline (9). in order to determine the agreement between the two reviewers, evaluation of inter-rater reliability in quality assessment of the articles was done. disagreements were resolved through discussion with a third researcher. 3. results 3.1. demographic characteristics of the articles our search in databases and non-indexed guidelines came up with 5988 records. excluding duplicate records, 4998 articles were found. reading their titles and abstracts and the full texts of these guidelines, and according to inclusion and exclusion criteria, 12 guidelines for pre-hospital pain management were included in this review (10-21). these guidelines were updated between 2012 and 2019 (figure 1). four guidelines were designed for managing pain in trauma patients (10, 12, 20, 21) and the other guidelines were developed for all conditions accompanying pain. all of the 12 included guidelines provided instructions on managing pain in adults, while 10 guidelines (11-20) reported pain management methods in children. table 1 demonstrates demographic characteristics of these guidelines. all of the above-mentioned guidelines emphasize on a standard method of pain evaluation. suggested tools in these guidelines for adults included numeric analog scale (nrs) and visual analog scale (vas), and for children included the face, legs, activity, cry, consol ability scale (flacc) or children’s hospital of eastern ontario pain scale (cheops scale), faces pain scale (fps) scale, fpsrevised, wong baker scale and nrs. 3.2. pain management in adults as mentioned previously, pain management in adults was reported in all of the 12 studies. different medications are suggested in these guidelines which include: fentanyl, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e55 panel 1: search query in medline search terms 1"emergency medical services"[mh] or "emergency health service"[tiab] or "emergency care"[tiab] or "prehospital medication"[tiab] or "prehospital care"[tiab] or "prehospital"[tiab] or "emergency services, medical"[tiab] or "emergency service, medical"[tiab] or "medical emergency service"[tiab] or "medical emergency services"[tiab] or "service, medical emergency"[tiab] or "services, medical emergency"[tiab] or "medical services, emergency"[tiab] or "emergency medical service"[tiab] or "medical service, emergency"[tiab] or "service, emergency medical"[tiab] or "services, emergency medical"[tiab] or "prehospital emergency care"[tiab] or "emergency care, prehospital"[tiab] or "emergicenters"[tiab] or "emergicenter"[tiab] or "emergency care"[tiab] or "emergency health services"[tiab] or "emergency health service"[tiab] or "health service, emergency"[tiab] or "health services, emergency"[tiab] or "service, emergency health"[tiab] or "services, emergency health"[tiab] 2patient controlled analgesia[tiab] or analgesic drugs[tiab] or drugs, analgesic[tiab] or anodynes[tiab] or analgesic agents[tiab] or agents, analgesic[tiab] or analgesics, non narcotic[tiab] or non-narcotic analgesics[tiab] or nonopioid analgesics[tiab] or analgesics, nonopioid[tiab] or non-opioid analgesics[tiab] or analgesics, non-opioid[tiab] or non opioid analgesics[tiab] or analgesics, nonnarcotic[tiab] or nonnarcotic analgesics[tiab] or antinociceptive agents[tiab] or opioid analgesics[tiab] or opioids[tiab] or partial opioid agonists[tiab] or agonists, partial opioid[tiab] or opioid agonists, partial[tiab] or opioid partial agonists[tiab] or agonists, opioid partial[tiab] or partial agonists, opioid[tiab] or full opioid agonists[tiab] or agonists, full opioid[tiab] or opioid agonists, full[tiab] or opioid full agonists[tiab] or agonists, opioid full[tiab] or full agonists, opioid[tiab] or opioid mixed agonist-antagonists[tiab] or agonist-antagonists, opioid mixed[tiab] or mixed agonistantagonists, opioid[tiab] or opioid mixed agonist antagonists[tiab] or narcotic[tiab] or narcotic analgesics[tiab] or analgesics, narcotic[tiab] or narcotic effect[tiab] or effect, narcotic[tiab] or narcotic effects[tiab] or effects, narcotic[tiab] or antiinflammatory agents, non steroidal[tiab] or nsaids[tiab] or non-steroidal anti-inflammatory agents[tiab] or non steroidal anti inflammatory agents[tiab] or nonsteroidal anti-inflammatory agents[tiab] or nonsteroidal anti inflammatory agents[tiab] or anti inflammatory agents, nonsteroidal[tiab] or antiinflammatory agents, nonsteroidal[tiab] or nonsteroidal antiinflammatory agents[tiab] or analgesics, anti-inflammatory[tiab] or anti-inflammatory analgesics[tiab] or aspirin-like agents[tiab] or aspirin like agents[tiab] or anesthetic drugs[tiab] or drugs, anesthetic[tiab] or anesthetic agents[tiab] or agents, anesthetic[tiab] or anesthetic effect[tiab] or effect, anesthetic[tiab] or anesthetic effects[tiab] or effects, anesthetic[tiab] or morphinan[tiab] or "acetaminophen"[mh] or "adapalene"[mh] or "adapalene, benzoyl peroxide drug combination"[mh] or "amantadine"[mh] or "amitriptyline"[mh] or "ampyrone"[mh] or "antipyrine"[mh] or "apazone"[mh] or "aspirin"[mh] or "bufexamac"[mh] or "carbachol"[mh] or "carbamazepine"[mh] or "celecoxib"[mh] or "clonixin"[mh] or "dexmedetomidine"[mh] or "diclofenac"[mh] or "diflunisal"[mh] or "dihydroergotamine"[mh] or "dipyrone"[mh] or "dronabinol"[mh] or "epirizole"[mh] or "ergotamine"[mh] or "etanercept"[mh] or "etodolac"[mh] or "etoricoxib"[mh] or "fenoprofen"[mh] or "feprazone"[mh] or "flurbiprofen"[mh] or "glafenine"[mh] or "ibuprofen"[mh] or "indomethacin"[mh] or "indoprofen"[mh] or "interleukin-2"[mh] or "ketoprofen"[mh] or "ketorolac"[mh] or "ketorolac tromethamine"[mh] or "masoprocol"[mh] or "meclofenamic acid"[mh] or "medetomidine"[mh] or "mefenamic acid"[mh] or "meloxicam"[mh] or "mesalamine"[mh] or "methotrimeprazine"[mh] or "milnacipran"[mh] or "nabumetone"[mh] or "naproxen"[mh] or "nefopam"[mh] or "niflumic acid"[mh] or "nitrous oxide"[mh] or "olopatadine hydrochloride"[mh] or "oxaprozin"[mh] or "oxyphenbutazone"[mh] or "phenacetin"[mh] or "phenylbutazone"[mh] or "piroxicam"[mh] or "pizotyline"[mh] or "quinine"[mh] or "resveratrol"[mh] or "salicylates"[mh] or "sodium salicylate"[mh] or "sulfasalazine"[mh] or "sulindac"[mh] or "suprofen"[mh] or "tolmetin"[mh] or "alfentanil"[mh] or "alphaprodine"[mh] or "buprenorphine"[mh] or "buprenorphine, naloxone drug combination"[mh] or "butorphanol"[mh] or "dextromoramide"[mh] or "dextropropoxyphene"[mh] or "dihydromorphine"[mh] or "diphenoxylate"[mh] or "ethylketocyclazocine"[mh] or "ethylmorphine"[mh] or "etorphine"[mh] or "fentanyl"[mh] or "hydrocodone"[mh] or "hydromorphone"[mh] or "levorphanol"[mh] or "meperidine"[mh] or "meptazinol"[mh] or "methadone"[mh] or "nalbuphine"[mh] or "opiate alkaloids"[mh] or "opium"[mh] or "oxycodone"[mh] or "oxymorphone"[mh] or "pentazocine"[mh] or "phenazocine"[mh] or "phenoperidine"[mh] or "pirinitramide"[mh] or "promedol"[mh] or "remifentanil"[mh] or "sufentanil"[mh] or "tapentadol"[mh] or "tilidine"[mh] or "tramadol"[mh] 3#1 and #2 morphine, ketamine, paracetamol, midazolam, nitric oxide, ketorolac, ibuprofen, methoxyflurane, nonsteroidal anti-inflammatory drugs, codeine, tramadol and aspirin. medication protocols are modified in these guidelines based on the severity of pain. 3.2.1 pre-hospital management of mild pain in adults five studies accurately proposed protocols for pre-hospital management of mild pain. mild pain is described as a severity less than 4, on a 0-10 pain scale. based on the guidelines included in the present systematic review, management of a patient with mild or endurable pain is prescribing oral paracetamol (1000mg or 15mg/kg). one guideline recommends that if a patient has weighs less than 60 kg, or is older than 60 or is malnourished, the suggested dose for paracetamol should be reduced to half. only one guideline suggests administration of ketorolac (30mg, iv/io or 60 mg, im) instead of paracetamol in relieving mild pain. this guideline proposes administration of nitric oxide in 50:50 dosage as an alternative treatment. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 4 figure 1: flow diagram of the present review. 3.2.2 pre-hospital management of moderate pain in adults 10 guidelines proposed instructions for pre-hospital management of moderate pain. moderate pain is described as a severity between 4 and 6 on a 0-10 pain scale. based on the guidelines included in the present systematic review, management of a patient with moderate pain is mainly done by prescribing morphine and fentanyl. however, two guidelines (15, 18) recommend administering paracetamol 1000 mg instead. using morphine in moderate pain management is mentioned unfavorable in naen guideline as well. rather, it is recommended to use fentanyl (1-2 µg/kg) or paracetamol (1000 mg) iv in 5 minutes (or as oral agent). assuming that the patient is hypovolemic or in shock, this guideline recommends using ketamine (0.25 mg/kg) and midazolam (1 mg) for pain alleviation (10). nice guideline, recommends using morphine as the first line treatment and ketamine as the second line (21). this guideline does not clarify the dosage and route of administration (table 2). intravenous paracetamol (five guidelines), ketamine (three guidelines), ketorolac (one guideline) and nonsteroidal anti-inflammatory drugs (one guideline) are other recommended options for adults’ pain management in prehospital conditions. although, one guideline (20) prohibits using nonsteroidal anti-inflammatory drugs in management of trauma patients (table 2). 3.2.3 pre-hospital management of severe pain in adults 12 guidelines proposed instructions on pre-hospital management of severe pain. severe pain is described as a severity of more than 6 on a 0-10 pain scale. based on the guidelines included in the present systematic review, prescribing morphine and fentanyl is the first line of treatment in pre-hospital managing severe pain. nevertheless, guidelines show some controversy. naen guideline 2014 suggests using fentanyl (1-2 µg/kg) infused with paracetamol (1000 mg). this guideline does not recommend using morphine. furthermore, naen guideline indicates that using ketamine (25 mg/kg iv ) infused with midazolam (1mg, iv ) and paracetamol (1000 mg iv ) (10) is preferable in cases with evidence of hypovolemia or insecure airways (10). administration of ketamine is recommended in four other protocols (11, 15, 16, 20) (table 2). intravenous paracetamol (two guidelines), nitric oxide (three guidelines), ibuprofen (three guidelines), ketorolac (two guidelines), methoxyflurane (three guidelines), nonsteroidal anti-inflammatory drugs (one guideline) and diamorphine (one guideline) are alternative options in prehospital management of severe pain in adults. one guideline suggested prescription of codeine and tramadol while another one recommended aspirin prescription (table 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e55 table 1: the characteristics of included guidelines name of guideline update date target patients age group organization level of evidence reference netherlands association for emergency nurses (naen) guideline 2014 trauma patients adults netherlands association for emergency nurses moderate (22) alabama department of public health ems (adphems) protocol 2018 patients with severe pain adults; pediatrics alabama state emergency medical control committee moderate (11) douglas county fire/ems (emergency medical services)(dcfems) guideline 2017 trauma patients with severe pain adults; pediatrics douglas county fire/ems (emergency medical services) moderate (12) ambulance tasmania clinical practice (atcp) guidelines for paramedics & intensive care paramedics 2012 general pain management adults; pediatrics ambulance tasmania high to moderate (13) north carolina college of emergency physicians (nccep) protocol 2019 general pain management adults; pediatrics north carolina college of emergency physicians high to moderate (14) clinical practice guideline of prehospital emergency care council (phecc) 2018 general pain management adults; pediatrics pre-hospital emergency care council moderate (15) ambulance victoria clinical practice (avcp) guideline 2018 general pain management adults; pediatrics australia ambulance victoria high to moderate (16) maryland institute for emergency medical services system (miems) guideline 2014 general pain management adults; pediatrics maryland institute for emergency medical services system moderate (7) italian intersociety recommendations on pain management (iirpm) in the emergency setting 2015 general pain management adults; pediatrics italian intersociety recommendations on pain management high to moderate (18) new mexico prehospital treatment (nmpht) guideline 2018 general pain management adults; pediatrics new mexico department of health moderate (19) u.s national association of ems physicians (naemsp) guideline 2014 trauma patients adults; pediatrics u.s naemsp medical directors council high to moderate (20) uk national institute for health and care excellence (nice) guideline 2016 trauma patients adults uk national institute for health and care excellence high to moderate (21) 3.3. pain management in children (under 14 years) as mentioned, pre-hospital pain management in children was reported in 10 of the included studies. in these guidelines, different medications were proposed, which included morphine, fentanyl, ketamine, paracetamol, midazolam, nitric oxide, ketorolac, ibuprofen, methoxyflurane, codeine, tramadol and hydromorphone. in these guidelines, instructions for using medications were different according to the severity of pain. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 6 table 2: recommendations for pre-hospital pain management in adults guideline pain severity morphine fentanyl ketamine paracetamol naen, 2014 moderate – 1-2 µg/kg every 3 mins (titrate medication on effect) if hypovolemia or shock state is present 0.25 mg/kg+ midazolam 1 mg 1000 mg iv for 5 min or 1000 mg oral severe – 1-2 µg/kg every 3 mins (titrate medication on effect) if hypovolemia or shock state is present 0.25 mg/kg+ midazolam 1 mg 1000 mg iv for 5 min titrate until nrs<4 adph-ems, 2018 severe 4 mg initial dose, titrate to pain relief in 2 mg every 3-5 mins, to an initial maximum dose of 10 mg cumulative maximum dose of 25 mg 1 µg/kg slow iv/im/in to an initial maximum dose of 50 µg. may repeat once. 0.2 mg slow iv to a maximum dose of 25 mg – or or 0.5 mg im and cumulative maximum dose of 50 mg 0.5 mg im to a maximum dose of 50 mg dcfems, 2017 severe 2-4 mg iv/io/im slowly titrate to pain relief to a maximum dose of 10 mg every 10 mins 25 µg iv/io slowly or 2 µg/kg in, titrate to pain relief to a maximum dose of 100 µg every 10 mins – – atcp, 2012 mild – – – 1000 mg atcp, 2012 moderate up to 0.05 mg/kg iv/io (initial maximum dose of maximum 5 mg), titrate to pain relief to a maximum dose of 20 mg every 5 mins up to 0.5 µg/kg iv/io (initial maximum dose of 5 mg), titrate to pain relief to a maximum dose of 200 µg every 5 mins if the iv access >10 mins delayed/unsuccessful up to 100 µg in, titrate to pain relief to a maximum dose of 400 µg every 5 mins – 1000 mg severe up to 0.05 mg/kg iv/io (initial maximum dose of maximum 5 mg), titrate to pain relief to a maximum dose of 20 mg every 5 mins up to 0.5 µg/kg iv/io (initial maximum dose of maximum 5 mg), titrate to pain relief to a maximum dose of 200 µg every 5 mins – – nccep, 2019 mild – – – 15 mg/kg oral moderate to severe 4 mg iv/io/im repeat 2 mg every 5 mins if required 50-75 µg iv/io repeat 25 µg every 20 mins to a maximum 200 µg – – phecc, 2018 mild – – – 1000 mg oral moderate – – – 1000 mg oral severe 4 mg iv, repeat 2 mg to pain relief to a maximum dose of 16 mg every 2 mins 100 µg in or 50 µg iv, repeat in once only after 10 min if needed 0.1 mg/kg iv, repeat once only after 10 min if needed 1000 mg iv this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e55 table 2: recommendations for pre-hospital pain management in adults (continue. . . ) guideline pain severity morphine fentanyl ketamine paracetamol avcp, 2018 mild – – – 1000 mg oral; 500 mg if weight < 60 kg or frail or elderly, malnourished or liver disease moderate up to 5 mg iv, titrate to pain relief every 5 mins (consult after 20 mg) up to 50 µg iv, titrate to pain relief every 5 mins (consult after 200 µg) – – or 200 µg in repeat up to 50 µg in every 5 minutes (consult after 400 µg) – – severe up to 5 mg iv, titrate to pain relief every 5 mins (consult after 20 mg) up to 50 µg iv, titrate to pain relief every 5 mins (consult after 200 µg) extreme traumatic pain persists to opioid: – or or 10-20 mg iv at 5-10 min intervals; 10 mg im, repeat 5 mg im after 15 minutes once only if required 200 µg in repeat up to 50 µg in every 5 minutes (consult after 400 µg) for severe pain 20-30 mg iv at 2 minute interval miems, 2014 moderate to severe 0.1 mg/kg iv/io, repeat 0.05 mg/kg iv/io to pain relief every 5 mins 1 µg/kg iv/io, repeat 0.5 mg/kg iv/io to pain relief every 5 mins – – iirpm, 2015 mild – – – 1000 mg moderate – – – 1000 mg severe 4-6 mg iv; 2-3 mg for patients aged >65 years and/or unstable patients 50-100 µg iv – – nmpht, 2018 moderate to severe 4-10 mg slow iv/io, titrating 2-4 mg every 10 mins with a maximum dose of 10 mg 25-100 µg iv/io – – naemsp, 2014 moderate 0.1 mg/kg im to a maximum initial dose of 15 mg 1 µg/kg in/im to a maximum dose of 100 µg 0.5 mg/kg in to a maximum initial dose of 25 mg and maximum cumulative dose of 100 mg 15 mg/kg oral to a maximum dose of 1000 mg severe 0.1 mg/kg iv/io to a maximum dose of 10 mg 1 µg/kg iv/io to a maximum dose of 100 µg 0.25 mg/kg im/iv/io to a maximum initial dose of 25 mg and maximum cumulative dose of 100 mg – nice, 2016 moderate to severe yes (iv first line; dosage not reported) – yes second line in – this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 8 table 2: recommendations for pre-hospital pain management in adults (continue. . . ) guideline pain severity midazolam nitric oxide ketorolac ibuprofen methoxyflurane nsaids naen, 2014 moderate – – – – – – severe – – – – – – adph-ems, 2018 severe – until pain control – – – – dcfems, 2017 severe – – – – – – atcp, 2012 mild – – – – – – moderate – – – – – – severe – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – nccep, 2019 mild – – – – – – moderate to severe – – – 10 mg/kg oral – – phecc, 2018 mild – 50:50 mix 30 mg iv/io or 60 mg im (maximum 60 mg) – – – moderate – – – 400 mg oral – – severe – 50:50 mix – 600 mg oral 3 ml, repeat once only if needed – avcp, 2018 mild – – – – – – moderate – – – – – – severe – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – miems, 2014 moderate to severe – – – – – – iirpm, 2015 mild – – – – – – moderate – – – – – yes (dosage not reported) iirpm, 2015 severe – – – – – yes (dosage not reported) nmpht, 2018 moderate to severe – – – – – – naemsp, 2014 moderate – – – – – contraindication in trauma severe – yes (dosage not reported) 30 mg im once only 10 mg/kg oral to a maximum dose of 800 mg – – nice, 2016 moderate to severe – – 15 mg iv once only – – – 3.3.1 pre-hospital management of mild pain in children four guidelines precisely proposed instructions on prehospital management of mild pain in children. according to the guidelines, control and management of pain in a child who is having mild pain include appeasing the child’s pain or at most prescribing paracetamol in a dose of 10-20mg/kg and ibuprofen in a dose of 4-10 mg/kg (table 3). 3.3.2 pre-hospital management of moderate pain in children eight guidelines provided advice on pre-hospital management of moderate pain. different medications are recommended for controlling and managing moderate pain in children. six of these guidelines suggest using intravenous (iv ), intranasal (in) or intra-osseous (io) fentanyl. also, five guidelines proposed using paracetamol with a 15 mg/kg dosage, and four guidelines referred to morphine as a treatment option (table 3). it is worth mentioning that only one guideline recommends intranasal ketamine in 0.5 mg/kg dosage for managing moderate pain (20). other recommended drugs in moderate pain management in children include methoxyflurane (three guidelines), ketorolac (two guidelines), nitric oxide (two guidelines), ibuprofen (two guidelines), and codeine and tramadol (one guideline) (table 3). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2019; 7 (1): e55 table 2: recommendations for pre-hospital pain management in adults (continue. . . ) guideline pain severity codeine tramadol hydromorphone diamorphine aspirin naen, 2014 moderate – – – – – severe – – – – – adph-ems, 2018 severe – – – – – dcfems, 2017 severe – – – – – atcp, 2012 mild – – – – – moderate – – – – – severe – – – – – nccep, 2019 mild – – – – – moderate to severe – – – – 324-650 mg oral phecc, 2018 mild – – – – – moderate – – – – – severe – – – – – avcp, 2018 mild – – – – – moderate – – – – – severe – – – – – miems, 2014 moderate to severe – – – – – iirpm, 2015 mild – – – – – moderate – – – – – iirpm, 2015 severe 30 mg oral 37.5 mg oral – – – nmpht, 2018 moderate to severe – – – – – naemsp guideline, 2014 moderate – – – – – severe – – – – – nice, 2016 moderate to severe – – – yes (dosage not reported) – mild to moderate – – – – – 3.3.3 pre-hospital management of severe pain in children 10 guidelines provided instructions on pre-hospital management of severe pain in children. the first line of treatment in pre-hospital management of severe pain in children is prescribing morphine and fentanyl. nine guidelines suggested using fentanyl (1-2 µg/kg iv/in/io or 25-50 µg in only) for severe pain management in children. also, eight guidelines recommended morphine (0.05-0.1 mg/kg) as a treatment option. three guidelines proposed intravenous, intranasal or intra-osseous ketamine as another option for pain management. furthermore, a guideline suggested using intravenous ketamine (0.25 mg/kg) only when there is a severe trauma pain in the limbs, which is not responding to opioids (16). paracetamol (one protocol), nitric oxide (one protocol only after consultation), ketorolac (two protocols), methoxyflurane (two protocols) and hydromorphone (one protocol) are other drugs recommended for strict pain management in children (table 3). 3.4. quality control of guidelines the overall score of the included guidelines varied from 4.5 to 6.5. aim and scope domain rating of the guidelines varied from 88% to 100%, stakeholder involvement domain varied from 72% to 100%, rigor of development domain varied from 12% to 81%, applicability domain varied from 79% to 100% and editorial independence varied from 8% to 50%. in the domain of clarity of presentation, the score of all studies was 100% (table 4). 4. discussion the current systematic review summarized the existing evidence on pre-hospital pain management, evaluating available guidelines and protocols. these guidelines provided instructions based on age groups (adults and children) and pain severity. the majority of guidelines recommended paracetamol as the medication of choice for management of mild pain in adults and children. for management of moderate to severe pain in pre-hospital setting, fentanyl and morphine are the first line choices. fentanyl is the first line treatment for children. although, some of the guidelines referred to ketamine as an alternative treatment for pain management, it seems that ketamine is still not the first line treatment in these conditions. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 10 table 3: recommendations for pre-hospital pain management in children guideline pain severity morphine fentanyl ketamine paracetamol adph-ems, 2018 severe 0.1 mg slow iv to a maximum dose of 5 mg 1 µg/kg slow iv/in to a maximum dose of 50 µg 0.2 mg slow iv to a maximum dose of 25 mg – or 0.5 mg im to maximum dose of 50 mg or 1 mg/kg in to a maximum dose of 50 mg dcfems, 2017 severe – 1-2 µg/kg iv/io slowly or 1-2 µg/kg in titrate to pain relief to a maximum dose of 100 µg every 10 mins – – atcp, 2012 mild – – – 15 mg/kg oral moderate – 25 µg in for small child (10-24 kg) 50 µg for large child (≥25 kg) titrate initial in dose to pain relief (maximum 3 doses) every 5 mins – 15 mg/kg oral atcp, 2012 severe last resort if pain not controlled up to 0.1 mg/kg im (maximum dose of 5 mg), single dose only 25 µg in for small child (10-24 kg) 50 µg for large child (≥25 kg) titrate initial in dose to pain relief – – or (maximum 3 doses) every 5 mins; up to 0.05 mg/kg iv, titrate to pain relief to a maximum dose of 0.2 mg/kg every 5 mins if pain not controlled up to 0.5 µg/kg iv, repeat a single dose to pain relief to a maximum dose of 2 µg/kg after 5 min nccep, 2019 moderate to severe 0.1 mg/kg iv/io/im repeat 0.1 mg/kg every 5 mins (maximum 10 mg) 1 µg/kg iv/io/im/in repeat 0.5 µg/kg every 5 mins (maximum 2 µg/kg) – – phecc, 2018 mild – – – 20 mg/kg oral moderate – – – 20 mg/kg oral severe 0.3 mg/kg po, for age≥1 year old, repeat 0.1 mg/kg to pain relief to a maximum dose of 0.1 mg/kg iv every 2 mins 1.5 µg/kg in, for age≥1 year old, repeat in once only after 10 min if needed 0.1 mg/kg iv, repeat once only after 10 min if needed if age≤1 years: 7.5 mg/kg iv if age>1 years 15 mg/kg iv avcp, 2018 mild – – – 15 mg/kg oral moderate – 25 µg in for small child (10-24 kg) 25 to 50 µg in for medium child (18 to 39 kg) repeat 3 doses if needed (consult after 3 doses) – 15 mg/kg oral this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2019; 7 (1): e55 table 3: recommendations for pre-hospital pain management in children (continue. . . ) guideline pain severity morphine fentanyl ketamine paracetamol avcp, 2018 severe 0.05 to 0.1 mg/kg iv, titrate to pain relief to a maximum dose of 0.2 mg/kg every 5-10 mins 25 µg in for small child (10-24 kg) 25 to 50 mg in for medium child (18 to 39 kg) repeat 3 doses if needed (consult after 3 doses) extreme traumatic pain persists despite opioid prescription 0.25 mg/kg iv at 5-10 min intervals (maximum 0.5 mg/kg) – miems, 2014 moderate to severe 0.1 mg/kg iv/io, repeat 0.05 mg/kg iv/io to pain relief every 5 mins 1 µg/kg iv/io, repeat 0.5 mg/kg iv/io to pain relief every 5 mins – – iirpm, 2015 mild – – – 10-15 mg/kg oral moderate – – – 15 mg/kg iv severe 0.05-0.1 mg/kg 1-2 µg/kg – – nmpht, 2018 moderate to severe 0.05 mg/kg iv/io/im 0.5 to 1 µg/kg iv/io – – naemsp, 2014 moderate 0.1 mg/kg im to a maximum initial dose of 15 mg 1 µg/kg in/im to a maximum dose of 100 µg 0.5 mg/kg in to a maximum initial dose of 25 mg and maximum cumulative dose of 100 mg 15 mg/kg oral to a maximum dose of 1000 mg severe 0.1 mg/kg iv/io to a maximum dose of 10 mg – 0.25 mg/kg im/iv/io to a maximum initial dose of 25 mg and maximum cumulative dose of 100 mg – however, it appears that ketamine should be prescribed instead of fentanyl if the patient is hypovolemic or the airway is not secure. overall, there is no strong evidence supporting the usage of ketamine in pain management. only two guidelines reported levels of evidence in detail. all of the other guidelines depicted a description regarding how the guideline was achieved and levels of evidence. indeed, levels of evidence presented in each guideline varied from the others. in general, levels of evidence presented for using fentanyl and morphine in pain management is moderate to high. in case of using ketamine, one guideline has referred to reported evidence as poor, and the other articles disregarded the usage of ketamine. overall, management of mild pain was mentioned as opioidfree in guidelines, while almost all the guidelines (except for two protocols in moderate pain management section) referred to fentanyl or morphine as the first line treatments for moderate to severe pain management. the two mentioned guidelines regarding management of moderate pain (15, 18) did not recommend using fentanyl and morphine and suggested using paracetamol with 1000 mg dosage instead. the majority of the guidelines provided single-drug protocols. only in special circumstances, such as shock, hypovolemia and unsecure airways, multidrug protocols are suggested. in this regard, the naen, 2014 guideline recommended that if a patient is hypovolemic or has no secure airways, ketamine in 0.25 mg/kg dosage with midazolam in 1 mg dosage should be administered. 5. conclusion the present systematic review has summarized the current evidence in pre-hospital pain management for the first time via investigation of guidelines and protocols concerning the matter. these guidelines presented instructions in age (adults and children) and pain severity categories. based on the obtained evidence, most of the guidelines recommend paracetamol as the treatment of choice for mild pain in both children and adults. for moderate and severe pain management, fentanyl and morphine are suggested medications for both adults and children, between these two medications, fentanyl is the treatment of choice for children. in conclusion, opioid-free protocols still have no place in pre-hospital management of moderate to severe pain. 6. appendix 6.1. acknowledgements none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 12 table 3: recommendations for pre-hospital pain management in children (continue. . . ) guideline pain severity midazolam nitric oxide ketorolac ibuprofen methoxyflurane nsaids adph-ems, 2018 severe – consult with online medical director – – – – dcfems, 2017 severe – – – – – – severe – – – – – – atcp, 2012 mild – – – – – – moderate – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – severe – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – nccep, 2019 moderate to severe – – 0.5 mg/kg iv/io/im (maximum 30 mg) – – – phecc, 2018 mild – – – 10 mg/kg oral – – moderate – 50:50 mix – 10 mg/kg oral 3 ml, for age≥5 years old repeat once only if needed – severe – – – – – – avcp, 2018 mild – – – – – – moderate – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – severe – – – – 3 ml (repeat 3 ml if required (maximum 6 ml) – miems, 2014 moderate to severe – – – – – – iirpm, 2015 mild – – – 4-10 mg/kg oral – – moderate – – – – – – severe – – – – – contraindication in trauma nmpht, 2018 moderate to severe – – – – – – naemsp, 2014 moderate – yes (dosage not reported) 1 mg im to a maximum dose of 30 mg 10 mg/kg oral to a maximum dose of 800 mg – – severe – – 0.5 mg/kg iv with a maximum dose of 15 mg – – – 6.2. authors contributions all authors met the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. authors orcids mahmoud yousefifard: 0000-0001-5181-4985 shaghayegh askarian-amiri: 0000-0001-8247-4485 arian madani neishaboori: 0000-0002-1920-9299 mostafa sadeghi: 0000-0001-7277-1726 peyman saberian: 0000-0003-1445-2756 alireza baratloo: 0000-0002-4383-7738 6.3. funding support this research has been supported by tehran medical service center grant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2019; 7 (1): e55 table 3: recommendations for pre-hospital pain management in children (continue. . . ) guideline pain severity codeine tramadol hydromorphone diamorphine aspirin adph-ems, 2018 severe – – – – – dcfems, 2017 severe – – – – – atcp, 2012 mild – – – – – moderate – – – – – severe – – – – – nccep, 2019 moderate to severe – – – – – phecc, 2018 mild – – – – – moderate – – – – – severe – – – – – avcp, 2018 mild – – – – – moderate – – – – – severe – – – – – miems, 2014 moderate to severe – – – – – iirpm, 2015 mild – – – – – moderate 1.5 mg/kg oral 1-2 mg/kg – – – severe – – – – – nmpht, 2018 moderate to severe – – – – – naemsp, 2014 moderate – – – – – severe – – 0.015 mg/kg im/iv/io to an initial maximum dose of 2 mg and cumulative maximum dose of 4 mg – – table 4: quality assessment of prehospital pain management guidelines based on agree ii recommendation guideline quality score (%) overall quality vote to recommend use domain 1 domain 2 domain 3 domain 4 domain 5 domain 6 score yes yes with no modification naen, 2014 100 100 29 100 96 33 4.5 1 1 0 adph-ems, 2018 100 94 25 100 79 50 6.0 2 0 0 dcfems, 2017 100 89 13 100 88 42 4.5 1 1 0 atcp, 2012 100 100 81 100 92 17 6.5 2 0 0 nccep, 2019 100 78 56 100 79 33 5.0 1 1 0 phecc, 2018 100 100 77 100 100 8 6.0 2 0 0 avcp, 2018 100 100 75 100 88 25 5.5 2 0 0 miems, 2014 100 100 81 100 92 33 5.0 1 1 0 iirpm, 2015 100 100 67 100 88 33 4.5 0 1 1 nmpht, 2018 89 72 13 100 79 42 4.5 1 1 0 naemsp, 2014 94 100 83 100 96 33 6.5 2 0 0 nice, 2016 100 100 81 100 96 33 6.5 2 0 0 domain 1: aim and scope; domain 2: stakeholder involvement; domain 3: rigor of development; domain 4: clarity of presentation; domain 5: applicability; domain 6: editorial independence. 6.4. conflict of interest none. references 1. borland ml, jacobs i, rogers ir. options in prehospital analgesia. emergency medicine. 2002;14(1):77-84. 2. demling r, youn y. the stress response to injury and critical illness. surgical critical care philadelphia: wb saunders. 1996;286. 3. moore ee, mattox kl, feliciano dv. trauma manual. new york: mcgraw-hill; 2003. 4. mauermann e, ruppen w, bandschapp o. different protocols used today to achieve total opioid-free general anesthesia without locoregional blocks. best practice & research clinical anaesthesiology. 2017;31(4):533-45. 5. samuel n, steiner ip, shavit i. prehospital pain 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treatment protocol in: emergency medical services, editor. north carolina, usa: the north carolina office of emergency medical services (nc oems); 2017. 15. medical advisory committee. clinical practice guidelines 2017 edition (updated 2018). in: council tp-hec, editor. ireland: pre-hospital emergency care council; 2018. 16. ambulance victoria. clinical practice guidelines ambulance and mica paramedics. in: ambulance victoria medical advisory committee, editor. melbourne, australia: ambulance victoria; 2018. 17. gausche-hill m, brown km, oliver zj, sasson c, dayan ps, eschmann nm, et al. an evidence-based guideline for prehospital analgesia in trauma. prehospital emergency care. 2014;18(sup1):25-34. 18. savoia g, coluzzi f, di cm, ambrosio f, della fc, oggioni r, et al. italian intersociety recommendations on pain management in the emergency setting (siaarti, simeu, sis 118, aisd, siared, sicut, irc). minerva anestesiologica. 2015;81(2):205-25. 19. new mexico emergency medical services. ems scope of practice guidelines for drugs. in: new mexico department of emergency medicine, editor. new mexico: new mexico department of department of health; 2018. 20. national association of state ems officials. national model ems clinical guidelines. washington, usa: national association of state ems; 2018. 21. excellence tnifhac. major trauma: assessment and initial management. london, uk: the national institute for health and care excellence; 2016. 22. scholten ac, berben sa, westmaas ah, van grunsven pm, de vaal et, rood pp, et al. pain management in trauma patients in (pre)hospital based emergency care: current practice versus new guideline. injury. 2015;46(5):798-806. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e17 le t t e r to ed i to r liver and kidney injuries in covid-19 and their effects on drug therapy; a letter to editor ali rismanbaf1∗, sara zarei2 1. department of clinical pharmacy and pharmacy practice, school of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran. 2. school of medicine, tehran medical sciences branch, islamic azad university, tehran, iran. received: march 2020; accepted: march 2020; published online: 9 march 2020 cite this article as: rismanbaf a, zarei s.liver and kidney injuries in covid-19 and their effects on drug therapy; a letter to editor. arch acad emerg med. 2020; 8(1): e17. dear editor, covid-19 is a newly emerging human infectious disease of sars-cov-2 origin that has affected many countries around the world. covid-19 is now rapidly spreading worldwide, and this letter is written as the world health organization (who) has declared a global emergency on january 31st amid concerns about a growing outbreak of sars-cov-2. most of the published articles on covid-19 have highlighted lungs as the main organ involved in the disease, while few articles have reported sars-cov-2 involvement in other organs, including liver and kidneys, which can impair the metabolism and excretion of the medications taken to treat the disease. according to zhang et al. the incidence of hepatic abnormalities significantly increases after infection with covid19 and during the course of the disease, which may indicate the effect of sars-cov-2 on the liver or side effects of the medications used by patients (1). also, xu et al. have reported steatosis and liver injury in the liver biopsy of a patient with covid-19 (2). in addition to liver injuries, some articles have also reported an increased incidence of acute renal injury following covid-19, which could be due to the presence of sars-cov-2, the inflammation induced by the disease, or a synergistic effect of both on kidneys (3, 4). additionally, cheng et al. have reported that patients with acute renal injury have a higher mortality rate compared to other patients (3). there is currently no definitive cure for covid19, and the treatment regimens prescribed for patients are the main treatments that have previously been effective in sars-cov and mers-cov, and chloroquine phosphate is the ∗corresponding author: ali rismanbaf; isfahan university of medical sciences, hezar jerib street, isfahan, iran. email: alirismanbaf74@gmail.com, tel: +989109747985 only medicine whose therapeutic effect has been proven by a clinical trial. medicines currently prescribed to treat covid19 include oseltamivir, lopinavir / ritonavir, ribavirin, and chloroquine phosphate or hydroxy chloroquine sulfate. all of these medicines are metabolized in the liver. most of the metabolites derived from oseltamivir, ribavirin and some of the metabolites of lopinavir / ritonavir, chloroquine phosphate and hydroxy chloroquine sulfate are found in the urine due to renal excretion. therefore, injury to the liver and kidneys can impair metabolism, excretion, dosing and expected concentrations of the medications, which can increase the risk of toxicity using the aforementioned medications. according to the reports, liver and kidneys can be damaged in patients with covid-19, which may make reaching the therapeutic dose of the medicines difficult and increase the risk of adverse drug reactions in patients. as a result, frequent and careful monitoring of liver and kidney functions in patients with covid-19 can lead to early diagnosis of liver and kidney disorders, and also help in achieving the optimal therapeutic concentrations and reducing the risk of adverse drug reactions. 1. declarations 1.1. author’s contribution all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. authors orcids ali rismanbaf : 0000-0001-8918-4229 sara zarei : 0000-0001-6217-9147 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. rismanbaf et al. 2 1.2. conflict of interest none. 1.3. funding and support none. references 1. zhang c, shi l, wang f-s. liver injury in covid-19: management and challenges. the lancet gastroenterology & hepatology. 2. xu z, shi l, wang y, zhang j, huang l, zhang c, et al. pathological findings of covid-19 associated with acute respiratory distress syndrome. the lancet respiratory medicine. 2020. 3. cheng y, luo r, wang k, zhang m, wang z, dong l, et al. kidney impairment is associated with in-hospital death of covid-19 patients. medrxiv. 2020. 4. xu d, zhang h, gong h-y, chen j-x, ye j-q, meng t, et al. identification of a potential mechanism of acute kidney injury during the covid-19 outbreak: a study based on single-cell transcriptome analysis. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2019; 7 (1): e50 or i g i n a l re s e a rc h risk factors of suicide death based on psychological autopsy method; a case-control study nafee rasouli1, seyed kazem malakouti1, mohsen rezaeian2, seyed mehdi saberi3, marzieh nojomi4, diego de leo5, abbas ramezani-farani6∗ 1. mental health research center, school of behavioral sciences and mental health (tehran institute of psychiatry), iran university of medical sciences, tehran, iran. 2. epidemiology and biostatistics department, rafsanjan medical school, occupational environmental research center, rafsanjan university of medical sciences, rafsanjan, iran. 3. legal medicine research center, legal medicine organization, tehran, iran. 4. preventive medicine and public health research center, psychosocial health research institute, department of community and family medicine, iran university of medical sciences, tehran, iran. 5. australian institute for suicide research and prevention, griffith university, brisbane, queensland, australia. 6. department of clinical psychology, school of behavioral sciences and mental health (tehran institute of psychiatry), iran university of medical sciences, tehran, iran. received: june 2019; accepted: july 2019; published online: 1 september 2019 abstract: introduction: investigation in each community can contribute to understanding the key factors involved in suicide death and its prevention. the present study aimed to investigate suicide death risk factors based on psychological autopsy method. methods: the present case-control study was conducted from april to september 2017, in tehran, iran, to compare two groups of people; those who died by suicide and controls (over the age of 18 years). data were collected by one interviewer via structured clinical interviews (scid-i), questionnaires used in the supremiss study, and the dickman impulsivity scale. results: each group consisted of 40 individuals. there was no significant difference between the case and control groups in terms of all demographic variables except for the level of education (p = 0.06) and occupational status (p = 0.009). the frequency of previous history of suicide attempt (p = 0.001), family history of suicide (p = 0.003), dsm iv axis i disorders (p = 0.006), and substance and alcohol consumption (p = 0.01) were significantly higher in the case group. the most commonly diagnosed disorders included mdd (45%) and substance use disorders (30%), respectively. the most common methods used in suicide included hanging (32.5%), and aluminum phosphide poisoning (32.5%) known as rice tablet. the strongest predictor of suicide death was the deceased person’s previous history of suicide attempt (or= 9.3; p = 0.04), smoking (or= 6.4; p = 0.006), unemployment (or= 5; p = 0.02), and dsm iv axis i disorders (or= 3.8; p = 0.04). conclusion: previous suicide attempt, smoking, unemployment, and suffering from at least one mental disorder were the significant predictors of suicide death. among mental disorders, major depressive disorder and substance use disorder were the most prevalent mental health problems. keywords: suicide; risk factors; mental disorders; depression; psychological autopsy cite this article as: rasouli n, malakouti s k, rezaeian m, saberi s m, nojomi m, de leo d, ramezani-farani a. risk factors of suicide death based on psychological autopsy method; a case-control study . arch acad emerg med. 2019; 7(1): e50. 1. introduction one person ends his/her life through suicide somewhere in ∗corresponding author: abbas ramezani-farani; department of clinical psychology, school of behavioral sciences and mental health, iran university of medical sciences, tehran, iran. tel: 00989194543139, email: ramezanifarani.a@iums.ac.ir, the world every 40 seconds; however, suicide is preventable. at least 6 people are directly affected by any suicide-related death (1). since suicide is a very sensitive issue, and even illegal in some countries (2, 3), it is likely to be reported less than the actual rate. an increasing trend in suicide rate has been revealed in iran through research in the last two decades (4). suicides and attempted suicides have increased from 8.3 per 100,000 population in 2001 to 19.4 in 2005 (5, 6). the stated this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. rasouli et al. 2 figure is smaller than most local reports that have been carried out as research studies (6); however, there is great variation in the prevalence of suicide in different regions of the country. western provinces of iran had the highest rate of suicide, from 10 to 20 suicide cases, per 100,000 people between 2006 and 2010. in 2012, the suicide rate per 100,000 people was 5.3 in both sexes, 3.6 in females, and 7.0 in males (1). each day, more than 13 people take their own lives by suicide in iran; most of whom are aged 15-35 years. the average nationwide rate of suicide has risen from 4.25 to 4.88 (from 2006 to 2010) and from 5.4 to 5.8 (2012-2017) according to the legal medicine organization (lmo) (7). psychiatric disorders are considered very important risk factors affecting suicidal behavior and earlier psychological autopsy (pa) studies have reported a strong relationship between mental disorders and suicide deaths. previous studies in developed countries showed that 60-90% of individuals who died by suicide had been suffering from at least one mental disorder (8, 9), with mood disorders being considered as the most commonly diagnosed conditions in most studies (10, 11). in addition, the prevalence of mental disorders varies based on gender in such a way that the prevalence of substance use and personality disorders were significantly higher in males, but mood disorders, especially major depressive disorder (mdd) were more common in females (8). psychological autopsy is a process that involves rewriting the deceased’s biography through psychological information extracted from personal records such as police records, medical records and interviews with family, friends, co-workers, and physicians. today, the psychological autopsy method has broader applications including the less ambiguous suicide death cases. risk factors, personality of the deceased person, and suicidal intentions and motives are investigated using different methods such as family interviews, suicide notes, etc. (12). psychological autopsy studies using a strong methodology have not been carried out in iran; therefore, investigating risk factors of suicide death cases in iran can help achieve a better understanding of these factors and be effective in preventing future suicide attempts. 2. methods 2.1. study design and setting the present case-control study was conducted from april to september 2017 to compare two groups of people, those who died by suicide and the control group. the sample size consisted of 40 individuals for each group. data were collected by one interviewer via structured clinical interviews (scid-i), questionnaires used in the supremiss study, and the dickman impulsivity scale. the protocol of study was approved by the ethics committee of iran university of medical sciences (ethical code: ir.iums.fmd.rec1396.9411). 2.2. participants the case group consisted of individuals over the age of 18 years, who died by suicide in tehran, the capital of iran. the controls were alive subjects homogenous with the suicide group in terms of age, gender, and place of residence. the study was performed initially by accessing the medical records of the deceased for six months from april to september 2017, through coordination with the legal medicine organization (lmo) of tehran. around 800 medical records susceptible to suicide were introduced to the investigator, which were scrutinized carefully considering inclusion and exclusion criteria. inclusion criteria included: 1) individuals who died by suicide at least 3 months before the study, 2) people over 18 years of age, 3) lack of ambiguity regarding the suicide cause of death as recorded in the medical records. the interval of 3 months was considered due to the following reasons: first, the mourning period has been partially passed and, second, there is lower risk of memory distortion in survivors within 3 months. using purposive and non-randomized sampling, eligible cases were contacted by telephone call (220 close relatives and families). the research objectives and manner of accessing the information were explained to each of the close relatives and families who accepted to take part in the study, via telephone contact. if they were willing to do so, face-to-face interview was arranged at the participant’s home. each interview lasted 2 hours, on average. the interviewees consisted of firstdegree family members, including 22 parents (18 of whom were mothers), 2 sons aged above 30 years, 8 spouses and 5 sisters, and 3 brothers, who were well aware of the symptoms and other characteristics of the deceased. the control subjects were selected purposively and non-randomly, and consisted of 30 males and 10 females who were selected from the accessible individuals who were living in tehran trying to match cases by gender and age. inclusion criteria were 1) not having history of suicide attempt; 2) being willing to cooperate in the project. 2.3. data gathering instruments supremiss study protocol was used for collecting the data in this study. this protocol includes a set of input questionnaire (items 1-14), demographic questionnaire (15-27), questionnaire on history of previous suicide attempt (s) and suicide ideation in the family (28-40), anger scale (56-65), alcohol and drug use questionnaire (66-77). spielberger’s state-trait anger scale (stas) this scale measures the severity of anger and includes 10 items. questionnaire on anger was developed in 1980. this is a self-report instrument designed in the 1970s. this instrument has been validated in iran in various studies including this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e50 those carried out by khodayarifard et al., in which the internal consistency and test-retest reliability coefficient of the above instrument were reported to be 0.60-0.93 and 0.72-0.93 (13). dickman impulsivity questionnaire this questionnaire was validated by ekhtiari et al. (2008) in iran. the internal consistency of cronbach’s alpha was 0.69 in healthy subjects and 0.74 in substance abusers. the cronbach’s alpha of dysfunctional impulsivity subscale was 0.48 in healthy subjects and 0.42 in substance abusers (14). the structured clinical interview for dsm-iv axis i (scidi) this provides a clinician administered semi structured scripted approach for evaluation of psychopathology and to determine current or lifetime presence of psychiatric diagnoses according to dsm-iv criteria (15). the diagnostic agreement for most of the specific and general diagnoses ranged from moderate to good (kappa coefficient higher than 0.6). in one study, the total kappa coefficient was reported to be 0.55 and 0.52 for lifetime and current diagnoses, respectively (16). 2.4. statistical analysis considering the minimum difference in the frequency of mental disorders in the suicide group (90%) with the control group (30%), based on the findings of cavanagh et al.’s (9) meta-analysis, and type i error=5% and power= 90%, sample size was determined as 20 cases. chi-square and t-test were used to compare qualitative and quantitative variables between the two groups, respectively. variables that were significantly different between the two groups were placed in the regression equation. some variables that had very high confidence interval were excluded from the regression analysis since they were significantly different between the two groups. 3. results 3.1. baseline characteristics of participants the suicide group consisted of 40 people (80% male; mean age = 39.4 ± 16; range =19-75); and the control group also consisted of 40 individuals who were homogeneous with the suicide group (75% male; mean age = 37.2 ± 13.7; range = 19-72). table 1 shows the baseline characteristics of studied subjects. there was no significant difference between the case and control groups in terms of all demographic variables except for the level of education (p = 0.06) and occupational status (p = 0.009). the frequency of previous history of suicide attempt (p = 0.0010), family history of suicide (p = 0.003), dsm iv axis i disorders (p = 0.006), and substance and alcohol consumption (p = 0.01) were significantly higher in the case group. the most commonly diagnosed disorders included mdd (45%) and substance use disorders (30%), respectively. the most common methods used in suicide included hanging (32.5%), and aluminum phosphide poisoning (32.5%) known as rice tablet. opioids (22.5%) had the highest prevalence rate among the substances used, which included opium (10%), heroin (7.5%), methadone (5%), and tramadol (7.5%). table 2 compares the frequency of mental disorders, anger, and impulsivity between case and control groups. 3.2. predictive factors of suicide the results of regression analysis revealed that the strongest predictor of suicide death was the deceased person’s previous history of suicide attempt (or= 9.3; p = 0.04), smoking (or= 6.4; p = 0.006), unemployment (or= 5; p = 0.02), and axis i disorders (or= 3.8; p = 0.04) (table 3). 4. discussion based on the findings of the present study, previous suicide attempt, smoking, unemployment, and suffering from at least one mental disorder were the significant predictors of suicide death. among mental disorders, major depressive disorder and substance use disorder were the most prevalent mental health problems. the present study is the first pa study of suicide in iran with case-control methodology and using structured interview with the study samples. according to the demographic data, the percentage of married and divorced people was higher in the suicide group, which is in line with the results of some other research studies (17, 18). according to the results of some previous studies in iran (19, 20), marital discord and parent-child generation gap, are the most prevalent stressors before attempting suicide. it may be concluded that, unlike some studies conducted in developed countries (21, 22), marriage is not necessarily a protective factor against suicide. in a review study, which included data from 16 provinces of iran, marital discord and family problems were the most common causes of suicide attempts (23). nevertheless, in developed countries, the risk of suicide in divorced men is twice that of single or widowers, but marital status was not influential in women in contrast with the finding of our study (24). the results of a study in japan showed that unemployment and divorce increase the risk of suicide by up to four times (25). however, studies in developed countries revealed that low marital integration was also associated with a higher risk of suicide (26). in northern ireland, the risk of suicide in single, divorced, and widowed men was greater and more significant than women (27). it seems that any change in marital status in terms of divorce, and widowhood in the first five-years of marriage can be a risk factor for suicide, which is related to the social, cultural, and family background of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. rasouli et al. 4 table 1: baseline characteristics of studied patients variables case (n=40) control (n=40) p value gender male 32 (80.0) 30 (75.0) 0.2 female 8 (20.0) 10 (25.0) age (years) mean ± sd 39.42 ±16.06 37.23 ±13.7 0.9 education high school diploma and higher 18 (45) 26 (65) 0.06 less than high school diploma 22 (55) 14 (35) marital status single 15 (37.5) 18 (45) married 20 (50) 21 (52.5) 0.2 divorced 5 (12.5) 1 (2.5) living arrangement lived alone 4 (10.0) 2 (5.0) with family members 35 (87.5) 34 (85.0) 0.2 with others 1 (2.5) 4 (10.0) occupational status unemployed 24 (60.0) 7 (17.5) 0.009 employed 16 (40.0) 33 (82.5) scid-i disorder no 7 (17.5) 30 (75.0) 0.006 yes 33 (82.5) 10 (25.0) history previous suicide attempt 17 (42.5) 1 (2.5) 0.001 family history of suicide attempt 7 (17.5) 0.003 history of substance and alcohol consumption 15 (37.5) 5 (12.5) 0.01 tobacco use 30 (75) 10 (25) 0.001 suicide method hanging 13 (32.5) aluminum phosphide poisoning 13 (32.5) jumping from a height 6 (15) self-injury 5 (12.5) na burning 1 (2.5) acid intake 1 (2.5) carbon monoxide poisoning 1 (2.5) drugs/substance abuse tranquillizers 4 (10.0) opioid 9 (22.5) cannabis 2 (5.0) crystal 7 (17.5) other 1 (2.5) data are presented as mean ± standard deviation (sd) or frequency (%). scid: the structured clinical interview for dsm-iv axis; na: not applicable. the society (28). regarding education, there was a significant difference between the two groups, which is consistent with previous studies (21, 29); suicide occurs more frequently among individuals with lower level of education and this is applicable in both genders and all age groups (30). low education can affect the chance of finding a suitable job and income, which has a significant impact on suicide attempts (31). most suicide attempters have education level of high school diploma, but the education level is lower among those who died by suicide (32). in terms of family support, in the current study, 87.5% of individuals lived with their family, 10% lived alone, and 2.5% lived with others. although most of the individuals in the suicide group lived with their families, it seems that the family were not able to provide enough supportive environment to prevent suicide. previous studies have shown that loss of family support significantly predicts suicide attempts before attempting suicide (33). therefore, it can be inferred that positive and supportive interpersonal relationships, and not just physically being together as a family, can play a more effecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e50 table 2: case-control comparisons of mental disorders, anger, and impulsivity variables case control p value major depressive disorder 18 (45.0) 2 (5.0) 0.003 bipolar disorders 6 (15) 1 (2.5) 0.04 anxiety disorders 7 (17.5) 7 (17.5) 1 psychotic disorders 6 (15.0) 0.01 substance-related disorders 12 (30.0) 0.001 scid-i disorder** 33 (82.5) 10 (25.0) 0.006 anger# 15.6 ± 8.4 9.9 ± 5.8 0.1 impulsivity* 9.8 ± 5.5 7.6 ± 3.9 0.2 data are presented as mean ± standard deviation (sd) or frequency (%). *: based on dickman impulsivity scale, #: based on spielberger’s state-trait anger scale (stas);**the structured clinical interview for dsm-iv axis i (scid). table 3: risk factors of suicide based on logistic regression model variables b s.e.* wald df or (95% ci) p value scid-i disorder 1.3 0.6 4.2 1 3.8 (1.06 –13.9) 0.04 unemployment 1.6 0.7 5.1 1 5 (1.2 – 20.2) 0.02 tobacco use 1.8 0.6 7.5 1 6.4 (1.7 – 24.5) 0.006 previous suicide attempt 2.2 1.1 3.9 1 9.3 (1.03 – 83.7) 0.04 *se: standard error; or: odds ratio; ci: confidence interval; scid: the structured clinical interview for dsm-iv axis. each of the variables predicting the suicide was reported at ≤0.05 based on the significance level tive role in preventing suicide attempts. the present study revealed that the deceased’s previous history of suicide was a strong predictor of suicide (or = 9). also other studies referred to the history of suicide attempt as a predictor of suicide (or = 2-24) (9, 29, 34). the present study also referred to unemployment as a strong predictor of suicide (or= 5). nevertheless, unemployment should be considered with other social factors simultaneously, but unemployment can be considered an important factor in suicide attempts, particularly in low-income countries. results of a study in iran showed that the human development index has negative correlation with suicide rate (7). results of a study on suicide attempters revealed that unemployment increases the risk of dying by suicide by 2.5 times (19). another study (35) also reported that unemployment along with other factors such as disease, economic problems, and poor supportive systems will affect suicidal behavior. tobacco use, was significantly higher in the suicide group compared to the control group (or = 6.4)(19). results of an autopsy study on suicidal behaviors in smokers (36) showed that more than 70% of deceased subjects were smokers, while smokers made up 50% of the population in the control group. previous research studies also showed a significant higher risk of suicide among heavy smokers than those who have rarely or never smoked (37), which may be due to the high incidence of other psychiatric disorders, and particularly major depression in smokers. some studies have shown that smoking cigarette may be a type of self-healing in depressed people (38). this relationship can also be inverse. also, some studies (39, 40) reported that smoking increases the risk of depression. in contrast to our expectation, impulsivity and aggression were not a good predictor of fatal suicidal behavior. many studies have referred to impulsivity as a major risk factor (41, 42). impulsive suicide attempts are usually seen in young, single, and aggressive type-b individuals. the average age of subjects participating in the present study was 39 years, which may justify such result (43, 44). results of a study in ilam, one of the western provinces of iran, showed that domestic violence and impulsivity could increase the risk of suicide by 1.1 to 3 times (45). garcãŋa et al. (2005) examined impulsivity in hospitalized patients and concluded that non-impulsive attempts increase the risk of death more than other attempts and are called ‘more fatal’ (46). however, if dangerous methods such as burning are used in impulsive attempts, the fatality rate is 80% (45)(47). in the present study, most of the subjects (around 50%) attempted suicide with prior planning, eleven had suicide notes and eight others had implicitly pointed to their suicide attempt, which could be considered as non-impulsive suicide attempt. this can be another reason for low impulsive and aggressive behavior among the subjects. mental disorders are a strong predictor of suicide and the treatment of these disorders can be very important in preventing suicide. the strength of this research was the use of scid to diagnose the disorders of deceased individuals by interviewing the first-degree relatives who had the closest relationship with them. one uncontrolled psychological autopsy study carried out in lorestan province, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. rasouli et al. 6 with high rate of suicide in iran, showed that 85% of the individuals had mental disorders at the time of death (48). results of a longitudinal study in ilam province, south western iran with high rate of suicide, showed that the rate of suicide caused by psychiatric diseases has increased from 17% to 26% over the past 16 years (49). our study showed that 82.5% of the deceased people suffered from axis i disorders, while such disorder was prevalent among 25% of the individuals in the control group. the results of other studies indicate that a high percentage (70.4%-88.6%) of the suicide cases had at least one axis i disorder (8, 11, 50). the present study showed that major depression and substance use disorders were the most prevalent disorders among the deceased (with prevalence of 45% and 30%, respectively), which is in line with some other studies (51, 52). a review study (8), which focused on high-income countries, reported that 87% of the suicide cases had at least one axis i disorder. however, this finding is not in line with some asian countries such as japan (65%, 72%), india (42%), hong kong (69%) and china (48%,63%) (10, 36, 50, 51, 53, 54); but, it is similar to taiwan (97% -100%) (55) and pakistan (96%) (56). the combination of multi-dimensional risk factors including suffering from mental disorder, unemployment, and smoking may cause a particular group of people with low education, married/divorced, with history of suicide attempt to end their own life by suicide. regarding the contribution of multiple risk factors in suicide, a comprehensive suicide prevention program is required particularly for geographic regions with high prevalence of suicide. conducting psychological autopsies in regions with high rate of suicide in iran, will make clear understanding of risk factors for suicide in different geographical areas to tailor the national and regional suicide prevention program. 5. limitation obtaining the consent of the deceased’s families and interviewing them was one of the challenging issues of conducting this study. since the present study required a long, indepth interview, there was a need for participants’ consent over their participation in the research and the provision of effective information on the deceased. 6. conclusion based on the findings of the present study, previous suicide attempt, smoking, unemployment, and suffering from at least one mental disorder were the significant predictors of suicide death. among mental disorders, major depressive disorder and substance use disorder were the most prevalent mental health problems. 7. appendix 7.1. acknowledgements this study is supported by the legal medicine organization (lmo) of tehran and financially supported by iran university of medical sciences (iums). also, we gratefully acknowledge the family members that participated in this study without any expectations. 7.2. author contribution nafee rasouli: design and drafting article, execution of the study abbas ramezani farani: design and execution of the study seyed kazem malakouti: design, training and drafting article mohsen rezaeian: design of the study seyed mehdi saberi: execution of the study marzieh nojomi: methodology and statistics diego de leo: critical review of article and comment authors orcids nafee rasouli: 0000-0001-8148-5422 abbas ramezani-farani: 0000-0001-6910-237x seyed kazem malakouti: 0000-0003-4978-6449 mohsen rezaeian: 0000-0003-3070-0166 seyed mehdi saberi: 000000025817-7701 marzieh nojomi: 0000-0003-4330-3522 diego de leo: 0000-0001-8255-6480 7.3. funding/support this study was financially supported by deputy of research, iran university of medical sciences. 7.4. conflict of interest the authors declare that there is no conflict of interest regarding the present study. references 1. who. preventing suicide: a global imperative. geneva: world health organization; 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1995;52(7):594-603. 56. khan mm, mahmud s, karim ms, zaman m, prince m. case-control study of suicide in karachi, pakistan. br j psychiatry. 2008;193(5):402-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e28 br i e f re p o rt seizure prevalence and its related factors in tramadol intoxication; a brief report asrin babahajian1, payam khomand2, farhad manoochehri3, roozbeh fakhimi3, behrooz ahsan2, mohiadin amjadian4, vahid yousefinejad1∗ 1. liver and digestive research center, kurdistan university of medical sciences, sanandaj, iran. 2. department of neurology, faculty of medicine, kurdistan university of medical sciences, sanandaj, iran. 3. school of medicine, kurdistan university of medical sciences, sanandaj, iran. 4. basic science department, kurdistan university of medical sciences, sanandaj, iran. received: march 2019; accepted: april 2019; published online: 7 may 2019 abstract: introduction: seizure is known to be a serious complication of tramadol consumption even in its therapeutic doses. the aim of this study was to determine the prevalence of seizure and its related factors in tramadol intoxicated patients referred to emergency department (ed). methods: in this cross-sectional study, all individuals, admitted to ed following tramadol intoxication were divided into two groups based on the presence or absence of seizures. demographic data as well as clinical, electroencephalogram and imaging findings were compared between the two groups using spss software version 22. results: 167 patients with the median age of 23 (13-45) years were studied (85% male). seizure was seen in 97 (58.0%) cases. risk of seizure had increased 3.7 times in patients with a history of seizure (or: 3.71 cl 95%: 1.17 11.76). tramadol dose was significantly higher in patients who had seizure more than once (median: 2800 iqr: 1800-4000), compared to those who had one seizure episode (median: 850 iqr: 1800-400) (p <0.0001). conclusion: based on the findings of this study, history of seizure increased the risk of seizure in patients taking tramadol, and the increase in dose correlated with a significant increase in seizure frequency. keywords: tramadol; seizure; toxicity; emergency service, hospital; risk factor cite this article as: babahajian a, khomand p, manoochehri f, fakhimi r, ahsan b, amjadian m, yousefinejad v. seizure prevalence and its related factors in tramadol intoxication; a brief report. arch acad emerg med. 2019; 7(1): e28. 1. introduction tramadol is a synthetic opioid drug with central effects, which is administered to relieve mild to severe pain. tramadol is an analogue of 4-phenylpiperidine codeine. it exerts its therapeutic effects by influencing opioid receptors (µ), noradrenergic system, serotonergic system and gabaergic system, and also by inhibiting reuptake of norepinephrine in the central nervous system (1). tramadol completely crosses the brain blood barrier. its maximum plasma concentration is seen 90 minutes after oral administration. its half-life is 5 to 6 hours. its excretion is more renal and its therapeutic concentration in the blood is about 100-300 ng/ml (2). tramadol can be given orally, subcutaneously, intra∗corresponding author: vahid yousefinejad; liver and digestive research center, kurdistan university of medical sciences, sanandaj, iran. tel: +98-8733247855 email: hooman56y@yahoo.com venously or suppository, but it has maximal absorption in oral administration. therapeutic dose is 50 mg in oral, 50100mg in injection and 100mg in anal administration. also, the maximum daily dose should not exceed 400mg (3). intoxication with tramadol may cause neurological complications such as seizure, respiratory arrest (apnea), and coma. the tramadol-induced seizure is often non-dose dependent and self-limited with generalized tonic-clonic feature (2). the neurotoxicity of tramadol occurs predominantly within the first 24 hours after ingestion and 84.6% of seizures occur in the first 6 hours after ingestion (4). the risk of seizure increases with concomitant use of tramadol with serotonin reuptake inhibitors (ssris), tricyclic antidepressants (tcas), and monoamine oxidase mao inhibitors (5). some studies have shown that tramadol could cause seizures in people with a history of epilepsy and in healthy people even at recommended doses, but most cases were observed among young people. opiate dependency, drug abuse and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. babahajian et al. 2 their complications were common in all age groups of both males and females in iran (6, 7). in recent years in iran, excessive intake and intoxication with tramadol has been one of the most common causes of admissions in emergency wards (4, 8-10). an increase in seizure frequencies because of tramadol intoxication was also reported. it was reported that 15 to 35% of patients with tramadol intoxication experienced seizures (10, 11). because of the increase in the number of tramadol users in recent years and, consequently, the increase of seizure associated with it, the prevalence of seizure and its related factors were evaluated in tramadol intoxicated patients in this study. 2. methods 2.1. study design and setting this cross-sectional study was done in the emergency department of tohid hospital, sanandaj, iran, from march 2016 to august 2018. tramadol intoxicated patients were divided into two groups based on the presence or absence of seizures, then demographic data as well as clinical, electroencephalogram and imaging findings were compared between the two groups. the protocol of the study was approved by the ethics committee of kurdistan university of medical sciences (nomuk1394/318). all participants gave written informed consent to participate in the study and the principles of confidentiality of data were respected by the researchers according to the helsinki declaration. 2.2. participants the study population consisted of all patients who had signs or symptoms of poisoning due to the use of tramadol (oral or injectable). seizures with metabolic causes such as hypocalcemia or hypoglycemia were excluded from the study. patients were selected and entered via consecutive sampling method. 2.3. data collection demographic data, clinical findings, dosage and duration of tramadol intake, history of seizure, time interval between taking tramadol and manifestation of seizure, type of seizure, concomitant use of other drugs, as well as the frequency of seizures were collected using a researcher-made questionnaire by two general physicians. then, the patients were divided into two groups based on the presence or absence of seizure. computed tomography (ct) scan was done for all patients at the time of admission. 2.4. statistical analysis minimum sample size required for the present study considering 95% confidence interval, 8% error, and 46.2% the prevalence of seizure following tramadol use (4), was calculated to be 150 cases. the results of the study were analyzed using spss v.22 software. qualitative data were reported as frequency and percentages, and quantitative data were reported as median and interquartile range (iqr) due to abnormal distribution of data. based on the incidence of seizure, patients were divided into two groups of with seizure and without seizure, then demographic characteristics and factors affecting seizure were compared in the two groups. to assess the relationship between quantitative and qualitative variables with seizure, mann-whitney u and chi-square tests were used. then, in order to determine the independent factors affecting seizure, variables with a p value <0.1 in the univariate analysis were entered into a multivariate logistic regression model and the data were reported as odds ratio (or) with 95% confidence interval (ci). spearman test was used to assess the correlation between tramadol intake dose and frequency of seizures. p<0.05 was considered as significance level. 3. results: 167 patients with the median age of 23 (13-45) years were studied (85% male). all patients took oral tramadol and the median dose of tramadol was 1200 mg (100 to 12,000 mg). seizure occurred in 97 (58.0%) patients. the frequency of seizure was one time in 80.4% and the type of seizure was a tonic-clonic type in 93.8% of cases. the median time interval between tramadol intake and seizure was 2 (1-12) hours. there was not any significant relationship between seizure occurrence and age (p = 0.39) and gender (p = 0.28). the incidence of seizure was significantly higher in patients with a history of seizure (p = 0.03). comparison of other risk factors between the two groups did not show any significant difference (table 1). in addition, the tramadol dose was significantly higher in patients who had seizures more than once (median: 2800 iqr: 1800-4000), compared to those who had seizures only once (median: 850 iqr: 1800-400) (r = 0.41; p <0.0001). the results of multivariate regression analysis showed that the history of seizure increased the risk of seizure in these patients by about four times (or = 3.71; 95% ci: 1.17 to 11.76; p = 0.03) (table 2). 4. discussion the findings of this study showed that 58.1% of patients with tramadol intoxication experienced seizures. the incidence of seizure was significantly higher in those with a history of seizure, and the dose of tramadol was significantly higher in patients who had experienced seizure more than once. tramadol intoxication rate showed a significant increase in iran like any other part of the world (12, 13), and in some studies in iran, the incidence of seizure was reported to be high in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e28 table 1: baseline characteristics of patients based of presence or absence of seizure variables seizure p without (n=97) with (n=70) age (year) median (percentile) 23.0 ( 21.0 -29.0 ) 22.0 ( 19.0 – 30.0 ) 0.39 gender female 12 (12.4) 13 (18.6) 0.28 male 85 (87.6) 57 (81.4) tramadol intake (mg) median (percentile) 1000 (500 – 2000) 1600 (800 -2850) 0.06 time to hospital admission (hour) median (percentile) 3.5 (2.0 – 5.0) 3.0 (2.0 -7.0) 0.35 history of seizure yes 17 (17.7) 4 (5.7) 0.03 no 79 (82.3) 66 (94.3) concomitant use of opioids yes 5 (5.2) 9 (12.9) 0.09 no 92 (94.8) 61 (87.1) concomitant use of other drugs yes 6 (6.2) 4 (5.7) 0.09 no 91 (93.8) 66 (94.3) episodes of seizure single seizure 78 (80.4) na multiple seizures 19 (19.6) data are presented as median (percentile 25-75) or frequency (%). na: not applicable. table 2: independent risk factors of seizure following tramadol intoxication variables odds ratio 95% ci p history of seizure 3.71 1.17 – 11.76 0.03 concomitant use of opioids 0.35 0.11 – 1.13 0.08 patients with tramadol intoxication. although excessive intake of tramadol was not life threatening, seizures sometimes increased mortality in these individuals (14-16). talaie et al., reported the incidence of seizure to be 46.2% (4). in another study, 48% of the 144 patients with tramadol intoxication experienced seizures (17). the precise mechanism of tramadol’s effect on seizure induction has not yet been determined. research showed that at high doses, tramadol had inhibitory effects on gamma aminobutyric acid (gaba) receptors (18, 19), and in animal models, inhibition of gaba receptors increased seizure severity (20). in addition, seizure was known to be a major side effect of tramadol which might occur with the use of both therapeutic and toxic doses (4, 21-26). also, the direct effect of tramadol on seizure has not been fully proven. in the present study, the median dose of tramadol was 1,000 mg (ranging from 100 to 1200 mg) in patients with seizure, which showed that none of the seizures was induced by the therapeutic doses, but when compared with the doses used in patients without seizure, there was no significant difference (p=0.06). this data showed that incidence of seizure in the patients was not dose-dependent. however, with an increase in the dose, the frequency of seizures increased. the dose of tramadol intake in patients who had more than one seizure was three times more than those with only one seizure, which showed a moderate correlation between drug dose and frequency of seizures. in the study by shadnia et al., in patients who had seizures more than once, tramadol intake dose was significantly higher compared to those who had seizure only once, which is consistent with the results of this study (24). however, in our study the correlation between the intake dose and the frequency of seizure was poor. considering that in both studies the tramadol dose assessment was done based on asking the patient or his relatives, confirmation of the relationship between the dose and the frequency of seizure requires more detailed studies. also, the results of this study showed that the risk of seizure had increased in patients with a history of seizure. based on this finding, it is recommended to take history of seizure in patients who might need tramadol administration, especially for long-term use. the limitation of this study was that the dose of the drug taken by each patient was determined based on his/her self-declaration, which is not very accurate and reliable. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. babahajian et al. 4 5. conclusion based on the findings of this study, a history of seizure increased the risk of seizure in patients taking tramadol, and an increase in the dose correlated with a significant increase in seizure frequency. it is recommended to take an accurate history of seizure in patients who might need tramadol administration, especially for long-term use. 6. appendix 6.1. acknowledgements this study was supported by vice chancellor for research, kurdistan university of medical sciences (grant number: 1394/318). 6.2. author contribution vahid yousefinejad, payam khomand, and behrouz ahsan designed the study. farhad manoochehri and rouzbeh fakhimi participated in acquisition of data. asrin babahajian analyzed the data. payam khomand and behrouz ahsan participated in management of data. vahid yousefinejad, mohiadin amjadian and asrin babahajian wrote the first draft and others revised the manuscript critically. all authors approved final version of the manuscript to be published and are accountable for all aspects of the work. authors orcids payam khomand: 0000-0001-6010-0706 behrooz ahsan: 0000-0002-2782-8911 mohiadin amjadian: 0000-0002-0589-3317 vahid yousefinejad :0000-0002-9928-938x 6.3. funding this study was supported by kurdistan university of medical sciences (grant number: 1394/318). 6.4. conflict of interest the authors declare that there is no conflict of interest. references 1. mood ne, sabzghabaee am, safdari a, yaraghi a. clinical signs, hospitalization duration and outcome of tramadol intoxication. journal of isfahan medical school. 2011;28(117). 2. boostani r, derakhshan s. tramadol induced seizure: a 3-year study. caspian journal of internal medicine. 2012;3(3):484. 3. mannocchi g, napoleoni f, napoletano s, pantano f, santoni m, tittarelli r, et al. fatal self administration of tramadol and propofol: a case report. journal of forensic and legal medicine. 2013;20(6):715-9. 4. talaie h, panahandeh r, fayaznouri mr, asadi z, abdollahi m. dose-independent occurrence of seizure with tramadol. journal of medical toxicology. 2009;5(2):63-7. 5. sansone ra, sansone la. tramadol: seizures, serotonin syndrome, and coadministered antidepressants. psychiatry (edgmont). 2009;6(4):17. 6. afshari r, majdzadeh r, balai-mood m. pattern of acute poisonings in mashhad, iran 1993–2000. journal of toxicology: clinical toxicology. 2004;42(7):965-75. 7. koushesh h, afshari r, afshari r. a new illicit opioid dependence outbreak, evidence for a combination of opioids and steroids. drug and chemical toxicology. 2009;32(2):114-9. 8. afshari r, tashakori a, shakiba a, editors. tramadol overdose induced cpk rise, haemodynamic and electocardiographic changes and seizure. clinical toxicology; 2008: informa healthcare 52 vanderbilt ave, new york, ny 10017 usa. 9. talaie h, panahandeh r, fayaznouri m, asadi z, abdollahi m, editors. seizure associated with tramadol use/abuse. clinical toxicology; 2008: informa healthcare 52 vanderbilt ave, new york, ny 10017 usa. 10. shadnia s, soltaninejad k, heydari k, sasanian g, abdollahi m. tramadol intoxication: a review of 114 cases. human & experimental toxicology. 2008;27(3):201-5. 11. kroenke k, krebs ee, bair mj. pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. general hospital psychiatry. 2009;31(3):206-19. 12. farzaneh e, samadzadeh m, shahbazzadegan b, sayadrezai i, mostafazadeh b, sarbandi farahani a, et al. comparing the frequency of seizure in patients intoxicated with tramadol treated with or without naloxone. journal of isfahan medical school. 2012;30(197). 13. soleymani f, shalviri g, abdollahi m. pattern of use and adverse drug reactions of tramadol; a review of 336,610,664 insured prescriptions during 5 years. int j pharmacol. 2011;7(4):757-60. 14. clarot f, goulle j, vaz e, proust b. fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality? forensic science international. 2003;134(1):57-61. 15. clarot f, proust b, vaz e, goulle j. tramadolbenzodiazepines and buprenorphine-benzodiazepines: two potentially fatal cocktails? journal of clinical forensic medicine. 2003;10(2):125-6. 16. musshoff f, madea b. fatality due to ingestion of tramadol alone. forensic science international. 2001;116(23):197-9. 17. rahimi hr, soltaninejad k, shadnia s. acute tramadol this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e28 poisoning and its clinical and laboratory findings. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2014;19(9):855. 18. hara k, minami k, sata t. the effects of tramadol and its metabolite on glycine, y-aminobutyric acida, and n-methyl-d-aspartate receptors expressed in xenopus oocytes. anesthesia & analgesia. 2005;100(5):1400-5. 19. rehni ak, singh i, kumar m. tramadol-induced seizurogenic effect: a possible role of opioid-dependent yaminobutyric acid inhibitory pathway. basic & clinical pharmacology & toxicology. 2008;103(3):262-6. 20. sun c, mtchedlishvili z, erisir a, kapur j. diminished neurosteroid sensitivity of synaptic inhibition and altered location of the α4 subunit of gabaa receptors in an animal model of epilepsy. journal of neuroscience. 2007;27(46):12641-50. 21. grond s, sablotzki a. clinical pharmacology of tramadol. clinical pharmacokinetics. 2004;43(13):879-923. 22. gholami k, shalviri g, zarbakhsh a, daryabari n, yousefian s. new guideline for tramadol usage following adverse drug reactions reported to the iranian pharmacovigilance center. pharmacoepidemiology and drug safety. 2007;16(2):229-37. 23. manocha a, sharma kk, mediratta pk. on the mechanism of anticonvulsant effect of tramadol in mice. pharmacology biochemistry and behavior. 2005;82(1):74-81. 24. shadnia s, brent j, mousavi-fatemi k, hafezi p, soltaninejad k. recurrent seizures in tramadol intoxication: implications for therapy based on 100 patients. basic & clinical pharmacology & toxicology. 2012;111(2):133-6. 25. brent j, burkhart k, dargan p, hatten b, megarbane b, palmer r, et al. critical care toxicology: diagnosis and management of the critically poisoned patient: springer; 2017. 26. jovanovic-cupic v, martinovic z, nesic n. seizures associated with intoxication and abuse of tramadol. clinical toxicology. 2006;44(2):143-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e33 le t t e r to ed i to r the rate of catheter-related infections using metal coated central venous catheters; a letter to editor seyed hossein ardehali1, mona jahangirian2, alireza fatemi3∗ 1. department of anesthesiology and critical care, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. internal medicine department, shohadaye tajrish hospital, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: april 2019; accepted: may 2019; published online: 25 june 2019 cite this article as: ardehali s h, jahangirian m, fatemi a. the rate of catheter-related infections using metal coated central venous catheters; a letter to editor. arch acad emerg med. 2019; 7(1): e33. dear editor blood infections due to intravenous catheters make up about 10% – 15% of hospital infections (1). in 2009, centers for disease control and prevention (cdc) reported the rate of blood infections related with using central venous catheter in the intensive care unit (icu) to be 1.65 in 1000 catheters per day (2). mortality due to infections related to central venous catheters has been reported to be between 12% and 25% in different studies. these infections have increased the duration of hospitalization by 12 days (3, 4). different approaches have been proposed for reducing these infections, among these approaches using aseptic methods, preventive antibiotics, disposable tools, and training the staff can be pointed out (5-7). among the methods considered in this regard is using catheters coated with antiseptic agents, antibiotics, and metals such as silver and platinum (8). some studies have suggested using these methods for reducing the mentioned infections and their consequences; however, their use is not currently agreed upon and their effect on reducing the infections caused by intravenous tools is still being studied. recently, these tools have become available in iran and since there is limited or insufficient experience working with them, the authors of the present letter designed a comparative study aiming to evaluate the role of central venous catheters coated with metals such as gold, silver, and palladium in the rate of catheter-related infections. in this study, 138 patients with the mean age of 60.62 ± 20.13 (17 – 97) years were randomly divided into 2 groups receiving ∗corresponding author: alireza fatemi; men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. tel: 00989128949858 email: dr_fatemi_alireza@yahoo.com either coated or non-coated central venous catheters, and then studied (58% male). the 2 groups were similar regarding sex (p = 0.730) and age (p = 0,409) distribution. 35 patients in the coated group and 42 in the non-coated group developed fever. finally, 22 (15.9%) cases of infection due to catheter were observed, 8 (36.4%) of which were in the coated group and 14 (63.6%) were in the non-coated group (p = 0.163). in culture, out of the 8 cases in the coated group, 4 cases of acinetobacter baumannii, 2 cases of klebsiella pneumoniae, 1 case of escherichia coli, and 1 case of staphylococcus aureus grew. the gram negative organisms found were all resistant to fluoroquinolone family, penicillin, aminoglycosides, third and fourth generation cephalosporins, carbapenems, and colistin. meanwhile, in culture of the 14 infectious cases found in the non-coated group, 10 cases had acinetobacter baumannii, 1 case had klebsiella pneumoniae, and in 3 cases escherichia coli had grown. all the mentioned organisms were resistant to fluoroquinolone family, penicillin, aminoglycosides, third and fourth generation cephalosporins, carbapenems, and colistin. in the end, 4 (50%) cases out of the 8 infected cases in the coated catheter group and 8 (57.81%) cases out of the 14 in the non-coated group died (p > 0.05). based on the results obtained in this study, it seems that despite the decrease in the number of infected cases when metal coated catheters were used, this difference is not statistically significant. the same finding is true when comparing the mortality rates of the 2 groups. therefore, considering the higher cost imposed on the patients for using these tools, more thought should be given to using them. of course, there is a need for more studies with more accuracy and control groups before the results of the present study can be generalized. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s h. ardehali et al. 2 1. appendix 1.1. acknowledgements the staff members of the intensive care unit of shohadaye tajrish hospital, who kindly cooperated with us in performing this study, are thanked. 1.2. author’s contribution all authors met the 4 criteria of authorship as recommended by the international committee of medical journal editors. authors orcids seyed hossein ardehali: 0000-0002-7662-0551 alireza fatemi: 0000-0003-0671-7611 1.3. conflict of interest the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support this study was supported by bactiguard through providing metal coated central venous catheters for patients. references 1. harrison tr, kasper dl, fauci as. harrison’s principles of internal medicine 19th ed: mcgraw-hill accessmedicine; 2015. 2. control cfd, prevention. vital signs: central line– associated blood stream infections–united states, 2001, 2008, and 2009. annals of emergency medicine. 2011;58(5):447-50. 3. raad i, hachem r, hanna h, bahna p, chatzinikolaou i, fang x, et al. sources and outcome of bloodstream infections in cancer patients: the role of central venous catheters. european journal of clinical microbiology & infectious diseases. 2007;26(8):549. 4. marschall j, mermel la, classen d, arias km, podgorny k, anderson dj, et al. strategies to prevent central line–associated bloodstream infections in acute care hospitals. infection control & hospital epidemiology. 2008;29(s1):s22-s30. 5. covey am, toro-pape fw, thornton rh, son c, erinjeri j, sofocleous ct, et al. totally implantable venous access device placement by interventional radiologists: are prophylactic antibiotics necessary? journal of vascular and interventional radiology. 2012;23(3):358-62. 6. crnich cj, maki dg. are antimicrobial-impregnated catheters effective? when does repetition reach the point of exhaustion? clinical infectious diseases. 2005;41(5):681-5. 7. hockenhull j, dwan k, boland a, smith g, bagust a, dundar y, et al. the clinical effectiveness and costeffectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation. nihr health technology assessment programme: executive summaries: nihr journals library; 2008. 8. chen y-m, dai a-p, shi y, liu z-j, gong m-f, yin x-b. effectiveness of silver-impregnated central venous catheters for preventing catheter-related blood stream infections: a meta-analysis. international journal of infectious diseases. 2014;29:279-86. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 98 emergency (2014); 2 (2): 98-100 case report thoracic pneumorrhachis in patient with lumbar fractures; a case report amir ghafarzad1, ali tagizadieh2, payman moharamzadeh1, kavous shahsavari nia3*, golnar majidi1 1. department of emergency medicine, tabriz university of medical sciences, tabriz, iran 2. critical care unit, tuberculosis and respiratory research center, tabriz university of medical sciences, tabriz, iran 3. road traffic injury research center, tabriz university of medical sciences, tabriz, iran abstract pneumorrhachis as a relatively rare condition may be an indication of substantial intra-spinal column injury. here we report a 39-year-old man was admitted because of low back pain and dyspenea after locating between motor vehicle and wall three days before admission. on arrival, physical exams and vital signs were normal. computed tomography (ct) scan showed bilateral pleural effusion, fracture of ribs number 8, 9 and 10 in lower left side of thorax, fracture of vertebra in l2-l4, and air bubbles in upper thoracic spinal canal. key words: pneumorrhachis; spinal cord; spinal fractures; case reports cite this article as: ghafarzad a, tagizadieh a, moharamzadeh p, shahsavari nia k, majidi g. thoracic pneumorrhachis in patient with lumbar fractures; a case report. emergency. 2014;2(2):98-100. introduction:1 neumorrhachis is defined as the presence of free intraspinal air. it is a relatively rare condition, typically benign and resolves with conservative therapies (1). this has been occasionally described in the surgical published work, usually in the context of thoracic surgery or as a complication of spinal instrumentation (2). it initially described by gordon and hardman in 1977 as intraspinal air (3). since then, especially with the advent of computed tomography (ct), there has been an increasing number of case reports describing the presence of air within the spinal canal (4). in 1987, newbold et al coined the term pneumorrhachis (5). pneumorrhachis may be an indication of substantial vertebral column injury, especially when paraspinal hematoma, rib fractures, transverse process fractures, clavicle fractures, subcutaneous air, intramuscular air, pneumothorax, or hemothorax are also present (2, 6-8). pneumorrhachis has also been reported with isolated head trauma and in the absence of an identifiable fracture within the skull or spine (9, 10). nontraumatic causes of pneumorrhachis include infection (11). despite known conditions that can result in pneumorrhachis the clinical significance and neurologic outcome for patients with pneumorrhachis remain *corresponding author: kavous shahsavari nia; emergency medicine department, imam reza hospital, tabriz university of medical sciences, golgasht avenue, tabriz, iran. postal code: 5166614756. phone/fax: +989125597918. email: kavous.shahsavari@yahoo.com received: 6 april 2014; accepted: 8 april 2014 poorly understood. here, we report a case of pneumorrhachis with fracture in lumbar spine and history of ankylosing spondylitis. case report: a 39-year-old man was admitted because of low back pain and dyspnea after locating between motor vehicle and wall 3 days before admission. he suffered from ankylosing spondylitis and was under corticosteroid therapy. on arrival, his glasgow coma scale was 15/15 with normal neurological examination. he was able to move his lower extremity, but it was limited by pain. in addition, he had intact sensation to light touch in all extremities. vital signs were stable and in radiographic examination, there was rib fracture in three ribs, hemothorax, subcutaneous emphysema, and lumbar vertebra fracture in l2-l4. there was no evidence of fracture or subluxation within the cervical spine. ct scan showed bilateral pleural effusion, fracture of ribs number 8, 9 and 10 in lower left side of thorax, fracture of vertebra in p figure 1: the axial thoracic spinal ct scan of patient  this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 99 ghafarzad et al l2-l4, and air bubbles in upper thoracic spinal canal (figure 1). the patient underwent lumbar surgery (laminectomy and cord decompression) and fusion of l2-l4 by screw. in according to neurosurgery consult no action performed on air bubbles. there was no neurologic deficit after treatment. discussion: pneumorrhachis, as the presence of free intra-spinal air, is also called aerorachia or epidural emphysema. it usually occurs in the epidural space but may be spread within the subarachnoid space with the distraction of dura meter (1). a significant increase in intra alveolar pressure and its rupture is the most common mechanism of pneumorrhachis. intra alveolar pressure was increased in several conditions such as acute asthma, recurrent vomiting and closed thoracic trauma. this led to alveolar rupture and air movement along the bronchovascular axis up to the mediastinum. the collected air then disassociates the pleura from the aorta and the parietal pleura from the spine, subsequently inflowing the extradural space via the intervertebral foramina (12). in addition, subarachnoid air may easily move cranially and caudally and may cause back and/or local pain and headache and/or nervous tissue compression (brain and spinal cord) by a valve mechanism. however, in the present case, there are not strong evidence of air diffusion between the pleura and the epidural space, it is the only pathophysiological mechanism stated in the literature (1). pneumorrhachis is most commonly identified on plain radiography or ct scan (13). magnetic resonance imaging is the most accurate investigation for the assessment of the extent of the condition. the natural history of pneumorrhachis is one of spontaneous resolution by diffusion. the best explanation for the radiologic findings in our patient is that air, under pressure in the pleural space, entered the spinal canal and then the subarachnoid space directly through tears of the parietal pleura and the spinal meninges. tension pneumothorax and thoracic spinal fracture should be considered in the differential diagnosis of both pneumorrhachis and pneumocephalus. intraspinal air is usually asymptomatic, self-limiting and resolves with conservative therapies, but in a rare number of cases, pneumorrhachis can cause cord compression and may even require decompressive surgery. therefore, quick assessment and diagnosis remain important (13). appropriate antibiotic prophylaxis must be considered, however, due to increased risk of infection of the underlying breach in the dura in traumatic etiologies (2). in comparison with others, sinha and mantle has been described a case of pneumorrhachis with rapid deterioration to death (14). lin et al reported a rare case of pneumorrhachis following lumbar puncture. the pneumorrhachis resolved spontaneously (15). in other study, they presented a case of tension pneumocephalus and pneumorrhachis secondary to a subarachnoid pleural fistula after thoracic spinal surgery (16). valente et al reported a 21-year-old male with severe pneumocephalus and pneumorrhachis who was made a full recovery without any neurological complication (17). the present report intends to increase awareness about pneumorrhachis among trauma patients. it is usually asymptomatic and self-limiting, but its presence should alert the attending trauma physician to carry out diagnostic workup for associated injury and treat the underlying cause (18). when seen in a trauma patient, pneumorrhachis may be pathognomonic of a serious unidentified spinal injury. acknowledgments: we would like to thank the patient's permission to use photos. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. ould-slimane m, ettori ma, lazennec jy, pascal-moussellard h, catonne y, rousseau ma. pneumorachis: a possible source of traumatic cord compression. orthop traumatol surg res. 2010;96(7):825-8. 2. hartig d, williams r. a case of pneumorachis as a consequence of thoracic spinal fractures. anz j surg. 2008;78(9):812-3. 3. gordon ij, hardman dr. the traumatic pneumomyelogram. a previously undescribed entity. neuroradiology. 1977;13(2):107-8. 4. oertel mf, korinth mc, reinges mh, krings t, terbeck s, gilsbach jm. pathogenesis, diagnosis and management of pneumorrhachis. eur spine j. 2006;15(5):636-43. 5. newbold rg, wiener md, vogler jb, 3rd, martinez s. traumatic pneumorrhachis. am j roentgenol. 1987;148(3):615-6. 6. goh bk, yeo aw. traumatic pneumorrhachis. j trauma. 2005;58(4):875-9. 7. katz ds, groskin sa, wasenko jj. pneumorachis and pneumocephalus caused by pneumothorax and multiple thoracic vertebral fractures. clin imaging. 1994;18(1):85-7. 8. yanagawa y, takasu a, sugiura t, okada y. a case of cervical pneumorrhachis induced by the combination of pneumomediastinum and root avulsion injuries. eur spine j. 2007;16(4):573-4574. 9. akay s, bayram b. traumatic pneumorrhachis: a rare entity of trauma. int j emerg med. 2008;1(1):53. 10. chibbaro s, selem m, tacconi l. cervicothoracolumbar pneumorachis. case report and review of the literature. surg this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com emergency (2014); 2 (2): 98-100 100 neurol. 2005;64(1):80-2. 11. thompson iii gr, crawford ge. pneumorachis caused by metastatic gas gangrene. diagn microbiol infect dis. 2009;63(1):108-10. 12. delval o, fossati p, tailboux l, mouillet b, tallon jb, vandermarcq p. epidural air after closed thoracic trauma. j radiol. 1998;79(6):566-8. [french]. 13. chaichana kl, pradilla g, witham tf, gokaslan zl, bydon a. the clinical significance of pneumorachis: a case report and review of the literature. j trauma acute care surg. 2010;68(3):736-44. 14. sinha p, mantle m. cervical pneumorrhachis: case reports. clin radiol. 2000;55(7):569-70. 15. lin l-c, liao y-m, yang r-c. pneumorrhachis following lumbar puncture: a case report. kaohsiung j med sci. 2006;22(1):39-43. 16. lin m, cheah f, ng s, yeo t. tension pneumocephalus and pneumorachis secondary to subarachnoid pleural fistula. br j radiol. 2000;73(867):325-7. 17. valente ma, bender ea. severe pneumocephalus after penetrating injury to the lumbar spine. int j case report image. 2012;3(4):23-5. 18. arora s, aggarwal p, cheema gs, singla j. pneumorachis of the cervical spine with associated pneumocephalus and subcutaneous emphysema. indian j orthop. 2011;45(4):3725. emergency. 2018; 6 (1): e38 or i g i n a l re s e a rc h acute lidocaine toxicity; a case series mitra rahimi1, mahboubeh elmi1, hossein hassanian-moghaddam1, nasim zamani1, kambiz soltaninejad2, reza forouzanfar1,3, shahin shadnia1∗ 1. excellence center of clinical toxicology, department of clinical toxicology, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of forensic toxicology, legal medicine research center, legal medicine organization, tehran, iran. 3. school of medicine, shahed university, tehran, iran. received: february 2018; accepted: june 2018; published online: 16 june 2018 abstract: introduction: parenteral form of lidocaine is the best-known source of lidocaine poisoning. this study aimed to evaluate the characteristics of acute lidocaine toxicity . methods: in this retrospective cross-sectional study, demographics, clinical presentation, laboratory findings, and outcome of patients intoxicated with lidocaine (based on icd10 codes) admitted to loghman hakim hospital, during april 2007 to march 2014 were analyzed. results: 30 cases with the mean age of 21.83 ± 6.57 year were studied (60% male). all subjects had used either 6.5% lidocaine spray or 2% topical formulations of lidocaine. the mean consumed dose of lidocaine was 465 ± 318.17 milligrams. the most frequent clinical presentations were nausea and vomiting (50%), seizure (33.3%), and loss of consciousness (16.7%). 22 (73.3%) cases had normal sinus rhythm, 4 (13.3%) bradycardia, 2 (6.7%) ventricular tachycardia, and 2 (6.7%) had left axis deviation. 11 (36.6%) cases were intubated and admitted to intensive care unit (icu) for 6.91 ± 7.16 days. three patients experienced status epilepticus that led to cardiac arrest, and death (all cases with suicidal intention). conclusion: based on the results of this study, most cases of topical lidocaine toxicity were among < 40-year-old patients with a male to female ratio of 1.2, with suicidal attempt in 90%, need for intensive care in 36.6%, and mortality rate of 10%. keywords: lidocaine; poisoning; drug-related side effects and adverse reactions; administration © copyright (2018) shahid beheshti university of medical sciences cite this article as: rahimi m, elmi m, hassanian-moghaddam h, zamani n, soltaninejad k, forouzanfar r, shadnia sh. acute lidocaine toxicity; a case series . emergency. 2018; 6(1): e38. 1. introduction l idocaine is an amide-type local anesthetic and a class ib antidysrhythmic agent, available since 1948. systemic exposure to large amounts of it leads to adverse effects on the cardiovascular and central nervous systems (cns). the primary mechanism of action is interrupting cardiac and neural signal conduction by hindering the influx of sodium ions via na+-channels. therefore, it can cause increased depolarization threshold and abortive action potential (1, 2). lidocaine toxicity is dosage-dependent and directly relative to its plasma concentration. likewise, the possibility of lidocaine toxicity is considered to be clinically significant at plasma concentrations higher than 6.0 mg/l (3-7). ∗corresponding author: shahin shadnia; department of clinical toxicology, loghman-hakim hospital poison center, kamali avenue, south karegar street, tehran, iran. tel/fax: +98-21-55424041 email: shahin1380@yahoo.com diagnosis is done based on clinical presentation, blood levels of lidocaine and imaging studies. anaphylaxis, anxiety disorders, cocaine toxicity, and conversion disorders should be considered in differential diagnosis of patients. the leading complications of lidocaine toxicity are cardiac arrest, local ischemia or nerve toxicities. management of lidocaine toxicity comes when airway compromises, and substantial hypotension, dysrhythmias, and seizures take place (8-10). parenteral form of lidocaine is the best-known source of poisoning, but poisoning could also happen with topical spray formulation (11). despite the importance of lidocaine toxicity, there is a scarcity of studies in this regard. the existing researches are limited to either intravenous or oral poisoning. here, we present clinical presentation, management, and outcome of acute poisoning cases with topical gel and spray forms of lidocaine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rahimi et al. 2 figure 1: clinical symptoms of patients on admission based on the consumed amount of lidocaine and their sex. 2. methods 2.1. study design and setting in this retrospective cross-sectional study demographics, clinical presentation, laboratory findings, management, and outcome of lidocaine intoxicated patients (based on icd10 definitions) admitted to loghman hakim hospital, from april 2007 to march 2014 were analyzed. this center is a unique referral poisoning center placed in the capital of iran, tehran. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences and researchers adhered to principles of helsinki recommendations. 2.2. participants all cases who met the icd10 codes of lidocaine toxicity who were referred to the emergency department (ed) of the mentioned hospital during the study period were evaluated without any sex or age limitation. patients with incomplete records, multidrug toxicity, and any history of seizure were excluded. 2.3. data gathering using documented patient profiles, a checklist containing demographics, clinical presentation, laboratory findings, and the outcome was filled out for all included patients by a senior toxicology resident. we converted the percentage amount of lidocaine per dose to milligrams in order to better report the results. intensive care unit (icu) admission indications were considered as loss of consciousness, seizures, cardiac dysrhythmias, and intubation. 2.4. statistical analysis data were analyzed using the statistical package for social sciences (spss) and p-value under 0.05 was considered statistically significant. continuous data were examined by student t-test if the data were normally distributed (indicated by kolmogorov-smirnov test); otherwise, mann–whitney utest was applied. categorical data were compared using pearson’s chi-square or fisher’s exact test. baseline demographics and screening measure variables were compared across groups using chi-square for categorical variables and onefactor (treatment) anova for continuous variables. 3. results 3.1. baseline characteristics 30 cases of lidocaine poisoning with the mean age of 21.83 ± 6.57 (10-40) years were admitted to ed during the study period (60% male). 18 (60%) cases were in 21-30 years age group, 11 (36.7%) were in 10-20 years group, and 1 (3.3%) was in 31-40 years age group. all subjects had used either 6.5% lidocaine spray or 2% topical formulations of lidocaine. the most prevalent cause of poisoning was suicide attempt (87.5%). the mean consumed dose of lidocaine was 465 ± 318.17 milligrams (11 cases < 500 milligrams and 19 cases ≥ 500 milligrams). the average elapsed time between exposure and admission to the emergency room was 5.1(1 – 76) hours. 3.2. clinical and para-clinical manifestations figure 1 shows the clinical symptoms of patients on admission based on sex and amount of lidocaine consumption. the most frequent clinical presentations were nausea and vomiting (50%), seizure (33.3%), and loss of consciousness (16.7%). metabolic acidosis was seen in blood gas analysis of all cases and 13 (43.3%) cases presented with some grades of loss of consciousness. table 1 summarizes clinical and laboratory findings of studied patients based on their intention. 22 (73.3%) cases had normal sinus rhythm, 4 had (13.3%) bradycardia, 2 (6.7%) had ventricular tachycardia, and 2 (6.7%) had left axis deviation on electrocardiography (ecg). brain computed tomography (ct) scan was performed in three patients, which revealed hypoxic-ischemic encephalopathy, and cortical atrophy. 3.3. management and outcome 18 (60%) patients were treated with supportive care such as intravenous fluid and anti-epileptic agents. 11 (36.6%) cases were intubated and admitted to intensive care unit (icu) for 6.91 ± 7.16 (1-24) days. three patients experienced status epilepticus that led to cardiac arrest, and death (100% with sucidal intention). mortality rate was 10%, and those who were discharged gained full this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e38 recovery. table 2 summarizes the characteristics of the three deceased individuals. 4. discussion based on the results of this study, most cases of topical lidocaine toxicity were among < 40-year-old patients with male to female ratio of 1.2, with a sucidal attempt in 90%, need for intensive care in 36.6%, and mortality rate of 10%. previous investigations demonstrated parenteral formulations of lidocaine as a source of accidental and intentional poisoning (12-19). in the united states in 2015, 1334 single exposures to lidocaine were reported (20). although in many case studies lidocaine toxicity has been reported to happen inadvertently, we found 27 cases (90%) of intentional ingestion in six years. to date, there is one case report with two fatal subjects of deliberate consumption (13). most of the studies indicated that following lidocaine use, only 35% of the consumed lidocaine reaches the systemic circulation and 65% of it is rapidly absorbed and digested by the liver hepatocytes. full elimination of lidocaine occurs with a half-life of 0.7-1.8 hours, and 3% of lidocaine is discharged unchanged in the 24-hour urine (21-23). nevertheless, the peak clinical signs and symptoms of lidocaine toxicity are observed 10-25 minutes after ingestion (12, 24, 25). the critical fact is that distribution kinetics are not so imperative in understanding the course of effects or toxicity of lidocaine when it is used for local anesthesia or after oral ingestion (26). there is no specific treatment for lidocaine toxicity. here, the majority of cases received supportive care (60%). thus, management is symptomatic to prevent hypoxia, acidosis, and hyperkalemia, which may increase the risk of cardiac toxicity. gastric decontamination is of partial value due to the quick absorption after ingestion. benzodiazepine and barbiturates can be prescribed to control local anesthetic-induced seizure. still, they may aggravate circulatory and respiratory depression. likewise, propofol has been used effectively to end the seizure in subjects with lidocaine toxicity(27, 28). studies proved that toxicity would increase by acidosis (29) and decreased by alkalosis (30). the majority of manifestations in this study owed to neurotoxicity of lidocaine that has been reported by other investigations as well (15, 31). the clinical symptoms after consumption of approximately two to more than 24 mg/ml of lidocaine are tongue numbness, dizziness, auditory and visual disorders, loss of consciousness, seizures, coma, and respiratory and cardiac arrest. eventually, in this study, three people underwent cardiac arrest all of whom had previous experiences of neurological symptoms including decreased level of consciousness and seizures. in this research, mortality rate was 10%. so far, in most of the studies, fatal cases of lidocaine toxicity were reported, either accidental or intentional. the considerable point here is that systemic toxicity of lidocaine can be life-threatening. hence, the rapid evaluation of clinical manifestations is essential to prevent mortality. in the current study, the mean consumed dosage of lidocaine was 465 ± 318.17 mg/ml. this study was performed retrospectively; therefore, we could not find any evidence of lidocaine assessment in the plasma samples. in general, lidocaine is dose-related, and toxicity may emerge at 8 mg/l or higher serum concentrations. researchers revealed that lidocaine toxicity could manifest by using high dosages of this remedy and system hypersensitivity in individuals (21). in this study, a significant portion of patients were male (60%), and the most frequent age range was 21-30 years. in one cdc survey between 1981-1983, 43,813 out of 51,880 workers with lidocaine toxicity were female (32). following reviewing all studies on “lidocaine poisoning/intoxication” in pubmed and google scholar databases, we found seven parallel studies. five of the cases occurred in women, three in men and one did not mention. the mean age of the victims was 47.25 years (12, 16, 33-37), which is higher than our results. the difference may be because of accidental poisoning in the elderly. this case series illustrated the relatively high suicidal rate in lidocaine poisoning and focuses on the management of such patients. clinicians need to be aware of the possible toxicity of topical or oral lidocaine and wisely review dosage schedules and discuss potential toxicity with patients in addition to allowing for alternative therapeutic modalities. 5. limitation since this was a retrospective study, the primary limitation was that the ingested dose of lidocaine was determined by taking a history of the patients and some patients may not have declared the exact dosage. besides, lidocaine blood level could not be evaluated because we do not have the equipment in iran. therefore, serum lidocaine concentrations must be determined in further studies. 6. conclusion based on the results of this study, most cases of topical lidocaine toxicity were among < 40 year old patients with a male to female ratio of 1.2, with suicidal attempt in 90%, need for intensive care in 36.6%, and mortality rate of 10%. 7. appendix 7.1. acknowledgements we would like to express gratitude to the staff of loghman hakim hospital who supported us in conducting this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. rahimi et al. 4 table 1: clinical and laboratory findings of intubated patients based on their intention parameter accidental (n=3) suicidal (n=27) p vital signs systolic blood pressure (mm hg) 106.67 ± 23.62 109.37 ± 21.88 0.948 diastolic blood pressure(mm hg) 72.50 ± 3.53 70.04 ± 12.68 0.523 pulse rate (beats/minute) 84.00 ± 10.58 84.30 ± 24.24 0.845 respiratory rate (beats/minute) 15.00 ± 4.24 17.54 ± 9.48 <0.001 presentation loss of consciousness (reed scale) 2.67 ± 2.30 1.33 ± 1.79 0.424 seizure 1 (3.3) 9 (30) <0.001 metabolic acidosis 0 (0) 8 (26.6) 0.197 laboratory findings lidocaine amount (milligrams)* 666.67 ± 288.67 442.59 ± 318.26 0.200 aspartate aminotransferase (u/l) 18.33 ± 0.57 36.04 ± 49.77 0.524 alanine aminotransferase (u/l) 13.00 ± 4.58 29.64 ± 41.72 0.391 total serum bilirubin (mg/dl) 0.53 ± 0.25 0.58 ± 0.45 0.543 creatinine (mg/dl) 1.70 ± 1.47 0.96 ± 0.24 0.016 sodium (mmol/l) 140.33 ± 2.30 142.19 ± 3.67 0.300 potassium (mmol/l) 3.73 ± 0.25 4.192± 0.72 0.130 bicarbonate (mmol/l) 22.50± 3.06 24.21 ± 6.75 0.475 serum glucose (mg/dl) 131 ± 45.39 119.81 ± 58.11 0.389 serum bun (mg/dl) 20.33 ± 3.78 24.88 ± 7.58 0.196 ∗: based on reports from patients or their companions. data are presented as mean ± standard deviation or number (%). table 2: complete characteristics of deceased cases of lidocaine poisoning variable case 1 case 2 case 3 demographics age (year) 20 21 27 sex male male male vital signs blood pressure (mmhg) 170/80 70/50 100/70 pulse rate (/minutes) 100 72 109 respiratory rate (/minutes) 12 12 12 paraclinical findings lidocaine amount (mg) 250 250 1000 conscioussness 4 3 4 icu stay (days) 15 2 3 metabolic acidosis positive positive positive brain ct findings ischemic encephalopathy ischemic encephalopathy – electrocardiographic findings ventricular tachycardia left axis deviation bradycardia clinical presentation stable convulsions, reduced consciousness, cardiac arrest generalized-tonic-clonic seizures, decreased consciousness, ventricular tachycardia, cardiac arrest stable convulsions, reduced consciousness, sinus bradycardia, cardiac arrest 7.2. author contribution this paper was based on dr. elmi’s thesis. dr. rahimi and dr. shadnia were the supervisor and advisor professors, respectively. they conceived the presented idea. dr. elmi gathered the data and performed the primary statistical analysis. dr. soltaninejad and dr. forouzanfar revised the primary form of the article. dr.hassanian-moghaddam and dr. zamani revised the final version of the study. all authors discussed the results, took part in preparing the final manuscript and agreed upon the concluding version of the document. 7.3. funding/support we received no funding or support for this work. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e38 7.4. conflict of interest the 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lih y, tsai t, liu c, leung h. lidocaine-induced cns toxicity–a case report. acta anaesthesiologica sinica. 1996;34(4):243-6. 36. lin s, wang s, tso h, hsieh y, shiao c, young t. a case report of possible lidocaine intoxication due to sprays of 8% lidocaine. acta anaesthesiologica sinica. 1994;32(3):219-22. 37. lie rl, vermeer bj, edelbroek pm. severe lidocaine intoxication by cutaneous absorption. journal of the american academy of dermatology. 1990;23(5):1026-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e24 or i g i n a l re s e a rc h value of ca-125 glycoprotein in predicting acute appendicitis; a diagnostic accuracy study mahboub pouraghaei1, kavous shahsavarinia1, farzad kakaei2, sevda gholipour-khalili3∗, babak mohammadpour1, payman moharamzadeh1, moloud balafar1 1. emergency medicine research center, tabriz university of medical sciences, tabriz, iran. 2. department of surgery and transplantation, tabriz university of medical sciences, tabriz, iran. 3. faculty of medicine, tabriz university of medical sciences, tabriz, iran. received: february 2019; accepted: march 2019; published online: 6 april 2019 abstract: introduction: carcinogen antigen 125 (ca-125) is a glycoprotein antigen, which has shown potentials in predicting peritoneal inflammation. the aim of this study is to determine the value of ca-125 in predicting acute appendicitis (aa). methods: this prospective diagnostic accuracy study was conducted on 15 – 70 year-old patients with acute abdominal pain, suspected to aa, referred to emergency department. the serum level of ca125 was measured for all patients before appendectomy and its screening characteristics in detection of aa case (confirmed by histology findings) were calculated and reported with 95% confidence interval (ci). results: 95 patients with the mean age of 31.65 ± 12.9 (15-75) years were studied (54.3% male). based on the histologic findings, 72 (75.8%) cases were categorized as aa (23 cases as severe). aa and non-aa (naa) groups were similar regarding the mean age (p = 0.59), mean duration of symptoms (p = 0.08), mean white blood cell (wbc) count (p = 0.37), and mean pmn percentage (p = 0.55). mean ca-125 level was 16.5 ± 20.0 u/ml in the aa group and 30.5 ± 6.1 u/ml in the naa group (p = 0.001). adjustment of analysis based on gender revealed a significant correlation between ca-125 level and diagnosis of aa only in females (34.23 ± 39 u/ml in naa versus 20.7 ± 26.7 u/ml in aa, p = 0.012). the area under the roc curve of ca-125 was 0.62 (95%ci: 0.51 to 0.72). sensitivity, specificity, npv, ppv, nlr, and plr of ca-125 in 16.4 u/ml cut off (best point) were 77.8% (95%ci: 66.4 86.7), 50.0% (95%ci: 28.2 71.8), 83.6% (95%ci: 76.7 88.7), and 40.7% (95%ci: 27.4 55.6), 0.44 (95%ci 0.2 0.8), and 1.56 (95%ci: 1.0 2.4), respectively. conclusion: considering the lower levels of ca-125 in patients with aa compared with naa cases and also weak screening performance characteristics, it seems that it could not be considered as an accurate screening tool in this regard. keywords: appendix; appendicitis; ca-125 antigen; biomarkers; abdominal pain cite this article as: pouraghaei m, shahsavarinia k, kakaei f, gholipour-khalili s, mohammadpour b, moharamzadeh p, balafar m. value of ca-125 glycoprotein in predicting acute appendicitis; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e24. 1. introduction acute appendicitis (aa) is one of the common causes of abdominal emergency surgeries. the possibility of one facing this condition over their lifetime varies between 6.7% to 8.6% (1, 2). the accurate and timely diagnosis of acute appendicitis plays an essential role in preventing life-threatening complications such as perforation associated with other morbidities or mortality (3). the diagnosis of appendicitis is made ∗corresponding author: sevda gholipour-khalili; imam reza hospital, golgasht street, tabriz, iran. postal code: 51666-14756 email: sevymed@yahoo.com phone: 00989144089490 based on clinical examination followed by laboratory and radiographic studies. these patients may undergo unnecessary hospital admissions and operations as the result of falsepositive diagnosis, while the false-negative findings can lead to extreme consequences (4). studies have shown that 40-83% of cases are detected based on the classic clinical symptoms (5-7). currently, laboratory parameters such as white blood cell count, neutrophil percentage, and c-reactive protein concentration are used in various combinations to improve sensitivity and specificity of assessments for determining risk of appendicitis (8, 9). carcinogen antigen 125 (ca-125) has shown potentials to be considered as a diagnostic test in this regard (10). ca-125 is a glycoprotein antigen, which is well known as a marker this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 2 figure 1: the area under the receiver operating characteristics (roc) curve of ca-125 in predicting acute appendicitis. for epithelial ovarian cancer. increased levels of ca-125 have been identified in benign and malignant conditions, including uterine leiomyoma, endometriosis, pelvic inflammatory disease, cirrhosis, and pleural or peritoneal effusion. different types of coelomic epithelial cells such as peritoneal mesothelial cells have a role in producing ca-125, which may increase in conditions of peritoneal inflammation (11). some studies have applied ca-125 as a diagnostic tool in aa, which found the serum level of ca-125 to be higher in patients suffering from appendicitis (10, 12). however, some researchers opposed this notion with results indicating absence of a predictive role for this tumor marker (13, 14). according to the divergent findings, the association between ca-125 and aa is not well understood. the aim of this study is to determine the value of ca-125 in predicting aa. 2. methods 2.1. study design and setting this prospective diagnostic accuracy study was conducted on patients with acute abdominal pain, suspected to aa, referred to emergency departments of imam reza and sina university hospitals, tabriz, iran, from 1st of january 2016 to the end of december 2017. the research protocol was confirmed by the ethics committee of tabriz university of medical sciences (tbzmed.rec.94/3-7/23) and all the participants gave informed written consent prior to the study. 2.2. participants using non-probability consecutive sampling method, the participants were chosen from patients between the ages of 15 to 70 years with acute abdominal pain suspected to acute appendicitis who were candidates for surgical appendectomy. patients with history of smoking, diabetes, hypertension or any medical conditions that associated with increased level of serum ca-125, such as cirrhosis, congestive heart failure, inflammatory bowel disease, malignancy, endometriosis, pregnancy and recent abdominal surgery were excluded. 2.3. procedure the serum level of ca-125 was checked for all patients (using 5 cc blood sampling from left/right brachial vein) in the emergency department before the operation. an electrochemiluminescence (ecl) assessment was done using e411 cobas machine and kits produced by germany roche company (based on company reference) for ca-125 measurement. in addition, routine laboratory testing including white blood cell (wbc) level and polymorph nuclear (pmn) cell percentage were also done for each patient. ultrasonography was also performed on each patient as part of the diagnostic approach. the gold standard for diagnosis of aa was positive histological findings described in pathology reports. patients with an alvarado score of 7 or above were considered for surgery. 2.4. data gathering a checklist consisting of patients’ demographic, clinical, and histopathological variables (after the surgery) was filled out for all patients by a senior emergency medicine resident under super vision of an emergency medicine specialist and supervisor of the project. the pathology reports were classified in three categories including negative for appendicitis, simple appendicitis or severe ones (phlegmonous, abscess, perforated or gangrenous appendix). 2.5. statistical analysis sample size was calculated as 93 patients, considering 60% sensitivity, 100% specificity and a confidence interval of 95%, and 80% power. statistical analysis was performed using spss software version 19.0 (ibm corp., armonk, n.y., usa). categorical variables were reported as percentages and continuous variables as mean ± standard deviation (sd). continuous variables were compared using independent t-test and categorical variables were compared via chi-square test. sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr), and negative likelihood ratio (nlr) as well as area under the receiver operating characteristics (roc) curve of ca-125 in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e24 table 1: comparison of the baseline characteristics between patients with acute appendicitis and those with normal appendix on histologic findings variable acute appendicitis p value yes (n=72) no (n=23) gender male 38 (52.7) 5 (21.7) 0.03 female 34 (42.3) 18 (78.3) age (year) mean ± sd 37.25 ± 44.8 29.73 ± 14.9 0.59 duration of symptoms (hour) mean ± sd 12.53 ± 16.9 11.32 ± 18.2 0.08 pmn (%) mean ± sd 75.1 ± 11.5 76.2 ± 12.2 0.55 wbc count (/ mm3) mean ± sd 12022.3 ± 3871.6 10209.5 ± 4387.4 0.37 data are reported as mean ± standard deviation (sd) or frequency (%). pmn: polymorph nuclear; wbc: white blood cell. predicting aa were calculated using medcalc software (version 18.2) and reported with 95% confidence interval (ci). pvalues less than 0.05 were considered as significant. 3. results 95 patients with the mean age of 31.65 ± 12.9 (15-75) years were studied (54.3% male). based on the histologic findings, 72 (75.8%) cases were categorized as aa (23 cases as severe) and the remaining 23 (24.2%) cases were normal (naa). table 1 compares the baseline characteristics of aa patients with others. the two groups were similar regarding mean age (p = 0.59), mean duration of symptoms (p = 0.08), mean white blood cell (wbc) count (p = 0.37), and mean pmn percentage (p = 0.55). 3.1. ca-125 level mean ca-125 level was 16.5 ± 20.0 u/ml in the aa group and 30.5 ± 6.1 u/ml in the naa group (p = 0.001). it was significantly higher in female patients (25.4 ± 31.8 vs 12.9 ± 10.7 u/ml; p = 0.03). adjustment of analysis based on gender revealed a significant correlation between ca-125 level and diagnosis of aa only in females (34.23 ± 39 in naa versus 20.7 ± 26.7 u/ml in aa, p = 0.012). adjustment of analysis based on severity of aa revealed an insignificant correlation between severity of aa and ca-125 level (p = 0.058). 3.2. screening characteristics of ca-125 figure 1 shows the area under the roc curve of ca-125 in identifying cases with aa. the area under the roc curve of ca-125 was 0.62 (95%ci: 0.51 to 0.72). based on the roc curve analysis, the best cut off point of ca-125 in predicting aa was estimated to be 16.4 u/ml. sensitivity, specificity, npv, ppv, nlr, and plr of ca-125 in 16.4 u/ml cut off were 77.8% (95%ci: 66.4 86.7), 50.0% (95%ci: 28.2 71.8), 83.6% (95%ci: 76.7 88.7), and 40.7% (95%ci: 27.4 55.6), 0.44 (95%ci 0.2 0.8), and 1.56 (95%ci: 1.0 2.4), respectively. 4. discussion in this study, we assessed the possible diagnostic value of ca125 in detecting aa. we hypothesized that patients with aa have higher ca-125 levels compared with naa patients. surprisingly, naa patients had higher ca-125 levels compared with aa patients. in the cut off value of 16.4 u/ml, ca-125 had a sensitivity of 77.8% and specificity of 50% in differentiating naa patients from aa cases. literature supported that some tumor markers such as ca125 may have additional value in not only the diagnosis of aa, but also the differentiation between severe complicated cases and simple cases (11). ca-125 is commonly used as a marker in gynecological cancers. considering the possible role of peritoneal cells in secreting ca-125 during the phase of inflammation, this biomarker may increase over the course of peritonitis resulting from aa. basaran et al. proposed that secretion of ca-125 starts six hours prior to the onset of inflammation (15). zeimet et al. compared the release of ca-125 from peritoneal cells and malignant ovarian cells. they reported higher ca-125 synthesis in peritoneal cells due to inflammation (16). it is also proposed that ca-125 is secreted by apical surface of mesothelial monolayers as a response to inflammatory cytokines such as interleukin-1 beta and tumor necrotizing factor-alpha, and e coli lipopolysaccharide (17). berger et al. reported a significantly higher ca-125 level in males with severe appendicitis compared to simple cases, whereas, ca-125 in males with aa didn’t differ significantly from naa patients. however, sevinc et al. found a significant positive correlation between ca-125 levels and aa diagnosis, which also decreased after the surgical appendectomy (11). in contrast, in the present study, the serum levels of ca-125 in patients with severe aa did not significantly differ from simthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 4 ple types of disease, even after the categorization of the study population based on gender. cetinkaya et al. also examined the correlation between ca125 and severe aa. they found high serum levels of ca-125 in severe aa cases with the cut off value of 35 u/ml. the calculated sensitivity, specificity, and ppvs were 60%, 100%, and 100%, respectively (18). in our study, the female group had significantly higher levels of ca-125. after analyzing ca-125 levels in gender specific subgroups, we found ca-125 levels to be higher in naa cases compared to aa cases in the female subgroup. however, there was not a significant correlation between ca-125 levels and aa diagnosis in the male group. secretion of ca-125 from ovarian cells in females may have affected the final results of the study. some of the previous researchers also evaluated ca-125 levels only in male cases. 5. limitation the study population was limited to 95 patients and in studies with larger sample groups the results may differ from the present report. in addition, we did not evaluate ca-125 levels after the surgery to compare cases with aa and naa. hence, more studies with larger study populations and with higher cut off values are required to assess the possible role of ca125 in aa diagnosis. 6. conclusion the results of the present study showed a low sensitivity and specificity for serum levels of ca-125 in differentiating patients with aa from those with naa. additionally, it was not an effective marker for diagnosis of the complicated form of aa. however, more research on a greater sample of patients is required to evaluate its predictive value. 7. appendix 7.1. acknowledgements we would like to thank yousef asgharzadeh and zahra seifar for their contribution to english editing of the paper. this study was retrieved from a medical dissertation conducted in tabriz university of medical sciences. 7.2. author contribution m.p. study design, k.s.n. and b.m study conduct, f.k. and m.p advisory, and supervision, b.m. and m.b data gathering and writing, p.m. and s.gh.k. analysis. authors orcids mahboub pouraghaei: 0000-0002-8421-6110 kavous shahsavarinia: 0000-0001-7359-4880 farzad kakaei: 0000-0003-1632-7393 7.3. funding/support this study was fully supported by tabriz university of medical sciences. 7.4. conflict of interest all the authors declared that there is no conflict of interest. references 1. chamisa i. a clinicopathological review of 324 appendices removed for acute appendicitis in durban, south africa: a retrospective analysis. ann r coll surg engl. 2009 nov;91(8):688–92. 2. ricci ma, trevisani mf, beck wc. acute appendicitis. a 5-year review. am surg. 1991 may;57(5):301–5. 3. stringer md. acute appendicitis. j paediatr child health. 2017 nov;53(11):1071–6. 4. omundsen m, dennett e. delay to appendicectomy and associated morbidity: a retrospective review. anz j surg. 2006 mar;76(3):153–5. 5. christian f, christian gp. a simple scoring system to reduce the negative appendicectomy rate. ann r coll surg engl. 1992 jul;74(4):281–5. 6. benito j, acedo y, medrano l, barcena e, garay rp, arri ea. usefulness of new and traditional serum biomarkers in children with suspected appendicitis. am j emerg med. 2016 may;34(5):871–6. 7. acar e, ozcan o, deliktas h, beydilli h, kirli i, alatas od, et al. laboratory markers has many valuable parameters in the discrimination between acute appendicitis and renal colic. ulus travma acil cerrahi derg. 2016 jan;22(1):17–22. 8. atema jj, gans sl, beenen lf, toorenvliet br, laurell h, stoker j, et al. accuracy of white blood cell count and creactive protein levels related to duration of symptoms in patients suspected of acute appendicitis. acad emerg med. 2015 sep;22(9):1015–24. 9. assarsson j, korner u, lundholm k. evaluation of procalcitonin as a marker to predict antibiotic response in adult patients with acute appendicitis: a prospective observational study. surg infect (larchmt). 2014 oct;15(5):601–5. 10. bilgic i, durdu t, gelecek s, yorulmaz s, karakilic e, ozmen mm, et al. ca-125 as a marker of peritoneal inflammation in diagnosis of acute appendicitis. int j multidiscip res dev. 2015;2(3):240-3. 11. sevinc b, turan e, kurku h, karahan o. role of ca125 in the diagnosis of acute appendicitis. journal of academic emergency medicine. 2017;16(2):62. 12. berger y, nevler a, shwaartz c, lahat e, zmora o, gutman m, et al. elevations of serum ca-125 predict severity of acute appendicitis in males. anz journal of surgery. 2016;86(4):260-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e24 13. allister l, bachur r, glickman j, horwitz b. serum markers in acute appendicitis. journal of surgical research. 2011;168(1):70-5. 14. kwan ky, nager al. diagnosing pediatric appendicitis: usefulness of laboratory markers. the american journal of emergency medicine. 2010;28(9):1009-15. 15. basaran a. ca-125 for diagnosis of acute appendicitis: new possibility for an old tumor marker. colorectal disease. 2010;12(2):155-6. 16. zeimet ag, marth c, offner fa, obrist p, uhl-steidl m, feichtinger h, et al. human peritoneal mesothelial cells are more potent than ovarian cancer cells in producing tumor marker ca-125. gynecologic oncology. 1996;62(3):384-9. 17. zeillemaker a, verbrugh h, van papendrecht ah, leguit p. ca 125 secretion by peritoneal mesothelial cells. journal of clinical pathology. 1994;47(3):263-5. 18. cetinkaya e, erdogan a, akgul o, celik c, tez m. high serum cancer antigen 125 level indicates perforation in acute appendicitis. the american journal of emergency medicine. 2015;33(10):1465-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e50 or i g i n a l re s e a rc h clinical characteristics of covid-19 infection in newborns and pediatrics: a systematic review latif panahi1, marzieh amiri2, somaye pouy3∗ 1. master student of nursing, student research committee, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. 2. department of emergency medicine, razi hospital, school of medicine, guilan university of medical sciences, rasht, iran. 3. phd student of nursing, student research committee, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. received: april 2020; accepted: april 2020; published online: 18 april 2020 abstract: introduction: world health organization has declared covid-19 a pandemic and a global health emergency. thus, it is necessary to clearly characterize clinical manifestations and management of covid-19 infection in children to provide accurate information for healthcare workers. accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with covid-19. methods: in this systematic review, medical databases including cochrane library, web of science, embase, scopus, sid, medline, who and litcovid were searched using english and persian keywords including covid19, pediatrics, newborn, coronavirus 2019, 2019-ncov, sars-cov-2. finally, data of 14 related articles were included in the study. results: a total of 2228 children, newborns and infants were studied. clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%). according to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate. no differences were found between male and female children regarding infection with covid-19. conclusion: most pediatrics were infected with covid-19 due to family cluster or history of close contact. infected children have relatively milder clinical symptoms compared to infected adults. we should pay special attention to early diagnosis and early treatment in children infected with covid-19. keywords: covid-19; severe acute respiratory syndrome coronavirus 2; child; infant; infant, newborn; coronavirus cite this article as: panahi l, amiri m, pouy s. clinical characteristics of covid-19 infection in newborns and pediatrics: a systematic review. arch acad emerg med. 2020; 8(1): e50. 1. introduction in late december 2019, with the onset of a series of viral pneumonia and the detection of covid-19, it spread rapidly throughout china and then the world (1-4). world health organization has declared covid-19 a pandemic and a global health emergency (5-8). according to who reports, 196 countries and regions have been affected, 413,467 people have been infected worldwide and 18,433 have died up to march 25, 2020 (9). iran is also one of the major countries ∗corresponding author: somaye pouy, phd student of nursing, student research committee, school of nursing and midwifery, guilan university of medical sciences, rasht, iran. tel: +98 (922) 1538452, e-mail: somayepouy@gmail.com involved with covid-19 and according to official statistics, 23049 cases have been confirmed and 1812 people have died by march 23, 2020 (10). coronaviruses are rna viruses from the coronaviridae family and coronavirinae subfamily. the novel coronavirus that has spread worldwide after emerging in wuhan is a beta-coronavirus (11-13). this virus has been labeled as severe acute respiratory syndrome coronavirus 2 (sars-cov-2) as its phylogenetic features are similar to sars-cov (14, 15). infection with covid-19 can be mild or severe and infected patients have clinical manifestation such as cough, high fever, chest pain, lethargy, weakness, muscular pain and diarrhea (16-18). many infected children and newborns with covid-19 have been identified all over the word. thus, it is necessary to clearly characterize clinical manifestations and management of covid-19 infecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 2 tion in this age group in order to provide accurate information for neonatologists and pediatricians. accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with covid-19. 2. methods 2.1. study design and setting the present study is a systematic review that was prepared according to the preferred reporting items for systematic reviews and meta-analysis (prisma) statement (19). 2.2. search process and search strategy in this review article, a comprehensive search was conducted on medical databases including cochrane library, web of science, science direct, embase, scopus, sid, medline, who and litcovid using english and persian keywords including covid-19, children, newborn, child, neonate, infant, adolescent, coronavirus 2019, 2019-ncov, sars-cov-2 between 1 january and 30 march 2020 using boolean logics including and, or, not. we used this example syntax in searching databases: (covid-19 or 2019-ncov or coronavirus 2019 or sars-cov-2) and (children or child or newborn or infant or neonate or adolescents or pediatric). initial search using these keywords yielded 983 articles that were assessed. after reviewing the titles and excluding duplicates, 60 relevant full-text articles remained. 46 of 60 articles were excluded due to lack of relevance to the purpose of the study or being a review article, letter to editor or commentary. finally, 14 full-text articles were included. moreover, we searched grey literature and used hand searching on references of articles that yielded 78 articles that were duplicates. details of the search process are presented in figure 1. 2.3. screening and inclusion criteria of articles inclusion criteria were: all articles published as case studies, case series, cohorts or observational studies from 1 december 2019 to 30 march 2020 using specific keywords in persian or english that dealt with characteristics of covid-19 infection in children. exclusion criteria were: articles published as letter to editor, review, or commentary. in order to reduce bias, data were collected by two researchers separately (sp and lp) and any disagreement was resolved through discussion with a third author (ma). most of the articles were performed in china and there were very few studies and reports on children from usa, italy, france or south korea, despite the high number of infected patients with covid-19 in those countries. among the included studies, 1 article was from singapore, 1 from japan and 12 articles were from china. 2.4. quality assessment we used the three statements of joanna briggs institute critical appraisal tools in order to assess the three types of included studies (case series, case reports and retrospective cohort studies). the quality appraisal tool for case reports, case series and retrospective cohort studies have 8, 10 and 11 items, respectively. therefore, the total score of quality assessment for articles using these checklists was 8, 10 and 11 respectively. their answers were: yes, no, unclear or not applicable (20). the quality scores of the evaluated papers are presented in table 1. 2.5. data extraction we designed a data extraction form to record information, which included the name of the researchers, country, year of study, type of research, sample size, history of exposure, clinical manifestations, underlying diseases, outcome, and quality assessment score of included studies. we used descriptive statistics to summarize the etiological, demographic, and clinical characteristics of pediatric covid-19 patients. 3. results 3.1. characteristics of included studies after searching the selected databases using mesh-matching keywords, 983 articles were obtained; furthermore, searching in grey literature and hand searching of references yielded 78 articles. after removing duplicates, 760 articles remained, 712 of which were removed due to irrelevancy to subject. finally, 48 full-text articles were assessed and 14 full-text articles were included (fig.1) (4, 21-33). the 14 included articles consisted of case studies, case series, correspondence, commentary and letter to editor, which were published about the clinical characteristics and management of children with covid-19. the characteristics of the studies are presented in table 1. 3.2. analysis of the reports a total of 2228 children, newborns and infants were studied. the age range of children was 1 day to 16 years and 70.32% were boys and 29.67% were girls, 740 children (32.1%) had confirmed test of covid-19 and 1488 (67.9%) were suspicious to covid-19 infection. studies have shown that children of all ages are at risk of developing covid-19, and there is no difference between children of different genders in this regard (4). the mean duration of infection with covid-19 to diagnosis ranged from 1 to 42 days. clinical manifestations of covid-19 in children have been reported as asymptomatic (92%) or with symptoms such as fever (96%), dry cough (91%), fatigue (45%) with mild upper respiratory tract symptoms (66%), abdominal pain (23%), nausea and vomitthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e50 table 1: characteristics of included studies study gender/age no cause onset ud severity of disease (%) clinical manifestations st qs outcome key findings dong et al. (2020) (4) china boy (56.6%) girl (44.4%)/ median: 7 years 2143 exposed to a covid-19 case or lived in an epidemic area 2 days (range: 0-42 days) nd asymptomatic: 4.4 mild: 50.9 moderate: 38.8 fever, respiratory symptoms or digestive symptoms, fatigue cohort study 7 recovered:2142 died: 1 • children at all ages appeared susceptible to covid-19. • clinical manifestations of children’s covid-19 cases were less severe than adult patients. ji et al. (2020) (23) china two boys: 9 and 15 years-old 2 travel history to covid-19 center 1-2 days no mild: 100 fever, pharyngeal congestion, mild diarrhea case series 8 recovered: 2 • infected children have relatively milder clinical symptoms than infected adults. yong park et al. (2020) (28) japan one 10 year-old girl 1 contact with infected family member 13 days nd mild: 100 fever case report 8 recovered: 1 • children are less infected and less ill with covid-19. zhu et al. (2020) (33) china boy (80%) girl (20%)/ one day-old newborn 10 born from infected mother with covid-19 and close contact after birth 1-9 days nd mild: 100 fever, shortness of breath, thrombocytopenia, rapid heart rate, vomiting case series 8 recovered:9 died: 1 • 2019-ncov infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress and even death. li et al. (2020) (25) china one boy and one girl 2 contact with infected family member 3-10 days nd mild :100 cough, runny nose case report 8 not discharged yet: 2 • infection with covid-19 is milder in children and recovery is faster. liu et al. (2020) (26) china 2 female/ 2 male: 2 & 11 month, 5 &9 years 4 exposure history nd nd mild: 100 fever, cough, fatigue cohort 9 recovered: 4 • exposure history and clinical symptoms were more helpful for screening in children versus chest ct. cui et al. (2020) (22) china a 55 days-old female infant 1 exposure to her infected parents and family 17 days no severe:100 rhinorrhea, dry cough case report 9 recovered: 1 • this case study highlights that children with covid-19 can also present with multiple organ damage and rapid disease changes like adults. wang et al. (2020) (31) china a 36 hours-old male 1 born from infected mother with covid-19 and close contact after birth immediately after birth no mild: 100 vomiting case report 8 recovered: 1 • vertical transmission of sars-cov-2 through placenta and its short-term and long-term harm to offsprings is still unclear. qiu et al. (2020) (12) china female: 46%; male: 64%/ age: 1-16 years 36 close contact with family members and history of exposure to the epidemic area nd nd mild: 47 moderate: 53 fever, dry cough cohort study 9 recovered: 36 • the high rate of asymptomatic children with covid-19 indicates the difficulty of identifying pediatric patients kam et al. (2020) (34) singapore a 6 months-old boy 1 close contact with family members 23 days no mild: 100 asymptomatic brief report 8 not discharged yet: 1 • infants can be asymptomatic despite high viral load ing (12%) and diarrhea (7%). but the most common manifestation of covid-19 was reported as fever and cough. acthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 4 table 1: characteristics of included studies study gender/age no cause onset ud severity of disease (%) clinical manifestations st qs outcome key findings zhou et al. (2020) (35) china female: 66.6% male: 33.3%/ median: 1-7 years 6 unknown 2-13 days7 no mild: 33.3 moderate: 50 severe: 16.6 fever, dry cough, vomiting case report 8 recovered: 6 • covid-19 in children can cause moderateto-severe respiratory illness jiehao et al. (2020)(36) china female: 70% male: 30%/ median: 6 years 10 close contact with family members and exposure to the epidemic area 2-10 days nd mild: 40 moderate: 60 fever, dry cough, sore throat, stuffy nose, sneezing case series 8 recovered: 10 • children with covid-19 usually present with milder respiratory infections, compared to adult cases zhang et al. (2020) (37) china female: 70% male:30%/ median: 6 years 10 born from infected mother with covid-19 immediately after birth no mild: 40 moderate: 60 fever, vomiting case series 7 recovered: 10 • timely termination of pregnancy will not increase the risk of premature birth and newborn asphyxia tang et al. (2020) (38) china a 10 year-old boy 1 close contact with infected covid-19 case 17 days nd mild: 100 asymptomatic case report 7 recovered: 1 • stool of covid-19 patients might serve as a vehicle for virus transmission nd: not determined; ud: underlying disease; qs: quality score; st: study type. cording to the included studies, the clinical types of covid19 in children were categorized in three domains including: mild (upper respiratory symptoms such as pharyngeal congestion, sore throat, and fever for a short duration or asymptomatic infection, positive rt-pcr test for sars-cov2, no abnormal radiographic and septic presentation), moderate (mild pneumonia, symptoms such as fever, cough, fatigue, headache, and myalgia, no complications and manifestations related to severe conditions) and severe (mild or moderate clinical features, plus any manifestations that suggest disease progression: rapid breathing (≥70 breaths per min for infants aged <1 year; ≥50 breaths per min for children aged >1 year), hypoxia, loss of consciousness, depression, coma, convulsions, dehydration, difficulty eating, gastrointestinal dysfunction, myocardial injury, elevated liver enzymes, coagulation dysfunction, rhabdomyolysis) (12). in the surveyed children, the severity of the disease was reported as mild (72%), moderate (22%) and severe (6%). most of the children (78%) were asymptomatic and only 5% of asymptomatic children developed clinical symptoms such as dyspnea or hypoxia, and 0.6% developed acute respiratory distress syndrome (ards) or multi-organ failure. also, all articles stated that, based on existing knowledge, the childhood illness is much less severe than that of adults and its cause is unknown. in this regard, we assessed underlying diseases of children, but most of them did not have any underlying disease (42.8%) and some studies did not state if underlying illnesses were present or not (57%). studies have also shown that lower respiratory tract involvement is rarely seen in children and most of them have upper respiratory tract involvement. most of the reported cases had improved within 1 to 2 weeks and were discharged from the hospital (99.72%); however, some remained under treatment (0.13%) or had died (0.089%). according to articles, two children had died. one of them was a 14-year-old boy who lived in hubei province, but no information was provided about his exposure history, underlying disease or comorbidity. the other case was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, and apgar score of 8, 8 (1 min and 5 min) and his symptoms included increased heart rate (first symptom), refractory shock and gastric bleeding. other complications included multiple organ failure and disseminated intravascular coagulation (dic). this newborn’s mother was 30 years old and had undergone cesarean section and her first symptom was fever, which began 3 days after delivery. her umbilical cord, placenta and amniotic fluid were normal. no premature rupture of membranes or intrauterine fetal distress was reported. these finding indicate that the mortality rates in children are very low. researchers stated that most of the children had been infected with covid-19 through family cluster infection and close contact with infected people (98.69%); some were infected through travel to epidemic center of covid-19 (0.089%) or due to an unknown origin (0.26%). in the studied children, for assessing covid-19 infection, samples were taken from nasopharyngeal secretions in 2208 cases (99.10%), from blood in 2144 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e50 figure 1: preferred reporting items for systematic reviews and meta-analyses (prisma) flowchart of the present study. cases (96.22%), from stool in 3 cases (0.13%), from saliva in 1 case (0.044%), and from oropharyngeal stations in 19 cases (0.85%). it was notable that in the 3 cases that stool samples were assessed for covid-19 infection, the result was positive 11-17 days (mean=15day) after symptom onset. so, one of the major concerns is the transmission of covid19 in children through fecal–oral route, because viral shedding has been found to take about 2-3 weeks after clinical manifestation of disease. therefore, fecal–oral transmission should be considered in addition to droplets in transmission of covid-19 in children and infants. studies, including predictors of disease severity, have indicated that chilthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 6 dren with younger age, underlying diseases, and immunodeficiency diseases are at higher risk for severe infection. so, infants and preschool-aged children are at greater risk of developing severe forms of the disease compared to older children. also, one of the most important methods of screening children with covid-19 is using exposure history and clinical symptoms, and unlike adults, chest ct scan findings are not valid in children. 4. discussion the present study surveyed the published literature on the clinical characteristics of covid-19 in infants and children. a literature review of studies demonstrated that children with covid-19 can be completely asymptomatic or have mild to moderate symptoms that can result in not being diagnosed (undocumented). findings of ogimi et al. showed that younger age, especially in children younger than school age, underlying diseases and immunosuppressive diseases are predictors of disease severity (39). in one study, li et al. indicated that about 86% of early infections with covid-19 in patients in china were undiagnosed (40). despite the low risk of infection transmission by undiagnosed cases, they are responsible for 79% of early infections (41). so, this raises concern about asymptomatic children that are taken care of by adults and elderly people, as they can be a source of covid-19 transmission. according to studies, children make up 2% of covid-19 cases in china, 1.2% in italy and 5% in us (9, 42, 43). these statistics are in line with those of sars epidemic, where only 6.9% of infected patients were children (41). according to early reports, presence of comorbidities including diabetes, hypertension, chronic respiratory disease and cardiac disease is a risk factor for poor prognosis in the adult population. studies showed that 67.2% of patients who died from covid-19 had a comorbidity (44). in our review article, we presented clinical features of children and their comorbidities (if present), but until now, no article has been published on the correlation between comorbidities and disease outcome in children. clinical manifestations of covid-19 that have been reported in children and infants include fever, dry cough, fatigue, symptoms of upper respiratory tract infection such as runny nose, and gastrointestinal symptoms such as anorexia, diarrhea, nausea and vomiting. the most common symptoms that have been reported are fever and dry cough. unlike adults, inferior respiratory tract involvement rarely occurs in children (17, 18, 22, 33). study of literature indicated that children of all ages were susceptible to covid-19, but were less likely than adults to develop symptoms (4, 20, 22). the underlying cause of the lower incidence and milder manifestations of covid-19 in children is obvious. children, especially younger children, have been infected with numerous viral infections. it is possible that repetitive exposure to numerous viruses can boost the immune system against sars-cov-2 infection. additionally, studies have shown that sars-cov-2 tends to attach to angiotensin-converting enzyme (ace), which is premature in children and this may result in a low rate of infection with sars-cov-2 (41, 42). it is very remarkable that various published articles reported high rates of lymphocytopenia. a study by guan et al., which was performed on 1099 patients with covid-19, showed that 82.3% of them had lymphocytopenia (45). while, in a study on 171 infected children, only 3.5% showed lymphocytopenia and in a study by henry et al. only 3% of children had lymphocytopenia (46). so, further studies are needed to assess the role of lymphocytes and severity of covid-19 in children. various studies have also found that most children have been infected with covid-19 due to family cluster transmission or close contact with the infected patient (20, 23). the study found that viral-shedding occurs more than 4 weeks after the onset of the disease, raising major concerns about fecal-oral transmission of covid-19 in children. fecal-oral transmission is especially very important in children who have not yet received toilet training, which is very important for infants and preschool aged children. therefore, parents need to be well educated in this regard(47). a study by dong et al. showed that gender had no effect on the incidence or severity of covid-19(4). in addition, vertical intrauterine transmission from pregnant mothers to newborns has not been reported yet. according to studies, samples taken from cord blood and placenta of pregnant women with positive covid-19 had negative results and one study reported that 30 newborns of covid-19 infected mothers had negative test results. also, it should be noted that most of these neonates, were born via caesarean section (40, 48, 49). according to the findings of liu et al., paying attention to clinical symptoms and history of exposure to covid-19 have high diagnostic value in children, while chest ct scan is not able to accurately detect the severity of the disease in children(28). in conclusion, the results of this study indicate that paying attention to children’s health is crucial during the covid-19 pandemic and that effective training should be given to parents. 5. limitation one of the important limitations of our study was that we could not use chinese databases and journals. also, we could not study the full-text of some of the chinese articles and we had to just rely on english-language summaries. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e50 6. declarations 6.1. acknowledgements the authors thank all those who contributed to this study. 6.2. author contribution latif panahi: study design, data collection, writing draft of study. marzieh amiri: study design, data collection, writing draft of study. somaye pouy: study design, data collection, writing manuscript, supervision of study. authors orcids latif panahi: 0000-0001-5157-2613 marzieh amiri: 0000-0002-1808-3815 somaye pouy: 0000-0003-3307-7840 6.3. funding/support no funding was provided for this study. 6.4. conflict of interest there is no conflict of interest. references 1. chen z-m, fu j-f, shu q, chen y-h, hua c-z, li f-b, et al. diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. world journal of pediatrics. 2020:1-7. 2. yu a, wang z, ren w, wu z, hu z, li l, et al. epidemic analysis of covid-19 in china after wuhan was restricted.2020. 1-19. 3. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-713. 4. dong y, mo x, hu y, qi x, jiang f, jiang z, et al. epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in china. pediatrics. 2020. 5. macintyre cr. global spread of covid-19 and pandemic potential. global 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fan l, et al. a 55-day-old female infant infected with covid 19: prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem l. panahi et al. 8 senting with pneumonia, liver injury, and heart damage. the journal of infectious diseases. 2020; jiaa113. 23. ji l-n, chao s, wang y-j, li x-j, mu x-d, lin m-g, et al. clinical features of pediatric patients with covid-19: a report of two family cluster cases. world journal of pediatrics. 2020:1-4. 24. kam k-q, yung cf, cui l, tzer pin lin r, mak tm, maiwald m, et al. a well infant with coronavirus disease 2019 with high viral load. clinical infectious diseases. 2020. ciaa201. 25. li y, guo f, cao y, li l, guo y. insight into covidâăř2019 for pediatricians. pediatric pulmonology. 2020:1-4. 26. liu h, liu f, li j, zhang t, wang d, lan w. clinical and ct imaging features of the covid-19 pneumonia: focus on pregnant women and children. journal of infection. 2020. 27. liu w, zhang q, chen j, xiang r, song h, shu s, et al. detection of covid-19 in children in early january 2020 in wuhan, china. new england journal of medicine. 2020; 382:1370-1371. 28. park jy, han ms, park ku, kim jy, choi eh. first pediatric case of coronavirus disease 2019 in korea. journal of korean medical science. 2020; 23;35(11):e124. 29. qiu h, wu j, hong l, luo y, song q, chen d. clinical and epidemiological features of 36 children with coronavirus disease 2019 (covid-19) in zhejiang, china: an observational cohort study. the lancet infectious diseases. 2020:1-8. 30. tang a, tong z, wang h, dai y, li k, liu j, et al. detection of novel coronavirus by rt-pcr in stool specimen from asymptomatic child, china. emerging infectious diseases. 2020;26(6). 31. wang s, guo l, chen l, liu w, cao y, zhang j, et al. a case report of neonatal covid-19 infection in china. clinical infectious diseases. 2020. ciaa225. 32. zhang l, jiang y, wei m, cheng b, zhou x, li j, et al. analysis of the pregnancy outcomes in pregnant women with covid-19 in hubei province. zhonghua fu chan ke za zhi. 2020;55:e009-e. 33. zhu h, wang l, fang c, peng s, zhang l, chang g, et al. clinical analysis of 10 neonates born to mothers with 2019-ncov pneumonia. translational pediatrics. 2020;9(1):51-60. 34. zhang jj, dong x, cao yy, yuan yd, yang yb, yan yq, et al. clinical characteristics of 140 patients infected by sarsâăřcovâăř2 in wuhan, china. allergy. 2020;00:112. 35. jin j-m, bai p, he w, wu f, liu x-f, han d-m, et al. gender differences in patients with covid-19: focus on severity and mortality. medrxiv. 2020.02.23.20026864. 36. li j-po, lam dsc, chen y, ting dsw. novel coronavirus disease 2019 (covid-19): the importance of recognising possible early ocular manifestation and using protective eyewear. bmj. 2020; 2020;104:297-298. 37. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. 2020; 395(10229): 1054-1062. 38. chan jf-w, yuan s, kok k-h, to kk-w, chu h, yang j, et al. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet. 2020;395(10223):514-523. 39. ogimi c, englund ja, bradford mc, qin x, boeckh m, waghmare a. characteristics and outcomes of coronavirus infection in children: the role of viral factors and an immunocompromised state. journal of the pediatric infectious diseases society. 2019;8(1):21-28. 40. liu w, tao z-w, lei w, ming-li y, kui l, ling z, et al. analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. chinese medical journal. 2020. 41. huang l, rong liu h. emotional responses and coping strategies of nurses and nursing college students during covid-19 outbreak. medrxiv. 2020.03.05.20031898. 42. liu z, han b, jiang r, huang y, ma c, wen j, et al. mental health status of doctors and nurses during covid-19 epidemic in china. available at ssrn 3551329. 2020. 43. li z, ge j, yang m, feng j, qiao m, jiang r, et al. vicarious traumatization in the general public, members, and nonmembers of medical teams aiding in covid-19 control. brain, behavior, and immunity. 2020. 44. maunder rg, lancee wj, balderson ke, bennett jp, borgundvaag b, evans s, et al. long-term psychological and occupational effects of providing hospital healthcare during sars outbreak. emerging infectious diseases. 2006;12(12):1924. 45. france nem, byers d, kearney b, myatt su. creating a healing environment: nurse-to-nurse caring in the critical care unit. int j hum caring. (1):44-48. 46. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 47. xing y-h, ni w, wu q, li w-j, li g-j, wang w-d, et al. prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019. journal of microbiology, immunology and infection. 2020. 48. jin j-m, bai p, he w, liu s, wu f, liu x-f, et al. higher severity and mortality in male patients with covid-19 independent of age and susceptibility. medrxiv. 2020. 49. kim y. nurses’ experiences of care for patients with middle east respiratory syndrome-coronavirus in south korea. american journal of infection control. 2018;46(7):781-787. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation declarations references archives of academic emergency medicine. 2020; 8(1): e37 le t t e r to ed i to r the covid-19 intubation and ventilation pathway (civp); a commentary muhammad akbar baig1∗ 1. department of emergency medicine, aga khan university hospital, karachi, pakistan. received: march 2020; accepted: march 2020; published online: 25 march 2020 cite this article as: baig m a. the covid-19 intubation and ventilation pathway (civp); a commentary. arch acad emerg med. 2020; 8(1): e37. in wake of the current covid-19 pandemic, which has taken the world by storm, it is imperative to protect the health and safety of physicians and staff involved in acute management of covid-19 patients. numerous studies have been published, establishing evidence and opinion-based guides for emergency physicians, who are at the front line. although many have established pathways for dealing with patient screening, testing, prognosis and disposition, i would like to discuss the management of the crashing patients in need of ventilation who we ought to be prepared for the most. as of now, it is essential to contain a crashing suspected/confirmed covid-19 patient within the confines of a negative isolation chamber due to a high risk of aerosolization, with strict adherence to personal protective equipment (ppe), exclusively comprising of n95 or preferably a powered air purifying respirator (papr) (1). most experienced staff should look after the patient, in order to minimize contamination to few personnel only. since conventional methods of non-invasive mechanical ventilation (cpap/bipap) are inadvisable due to aerosol generation, it is suggested to secure a definitive airway with extreme precaution (2). pre-oxygenation can be performed with a bag valve mask device with positive end expiratory valve and a viral filter, if available. it is recommended to form a good facemask seal with both hands, while making sure not to deliver any positive breaths (2). induction and relaxant medications should be administered at a maximum dose in order to prevent cough or gag reflex during the procedure (3). a video laryngoscope should be used so as to avoid having the operator position their face close to the patient. the most senior physician should at∗corresponding author: muhammad akbar baig; department of emergency medicine, aga khan university hospital, stadium road, karachi, pakistan. tel: 0092-315-2218758, email:dr_akbar2007@hotmail.com tempt maintaining the airway, in order to maximally ensure first pass intubation success; however, in a failed airway scenario, attempts should be made to establish a surgical airway immediately. the endotracheal tube (ett) should be positioned at a predetermined depth and secured properly. avoid auscultation attempts to prevent instrument contamination, and look for bilateral chest rise or end tidal capnography waveform. if available, a viral filter should be connected to the adapter of the ett, and another should be placed at the exhalation port of the ventilator (2). a plastic transparent sheet can be placed over the patientâăźs head and chest to prevent droplet spread (4). all contaminated instruments should be placed in a transparent bag for immediate disposal and/or decontamination. the ardsnet (acute respiratory distress syndrome network) protocol should be followed for patient ventilation. in case of poor pao2/fio2(pf) ratio (<150), place the patient in prone position (5). allow for permissive hypercapnia (ph > 7.2), if hemodynamics remain stable (6, 7). do not give fluid boluses and maintain the patient in negative balance (8). if needed, place a central venous access line in femoral site for administering vasopressors to maintain adequate mean arterial pressure. following intubation and initial ventilation, immediately proceed to transfer the patient to intensive care unit, after which, perform decontamination of the initial zone and the equipment used. consider meticulous removal of ppe and debrief. 1. declarations 1.1. acknowledgements none. 1.2. author’s contribution the primary author is responsible for the conception, drafting and final approval of the article. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m a. baig 2 authors orcids muhammad akbar baig: 0000-0002-2830-9099 1.3. conflict of interest none to declare. 1.4. funding and support none to declare. references 1. centers for disease control and prevention. interim clinical guidance for management of patients with confirmed coronavirus disease (covid-19) 2020 [cited 2020 18 march]. available from: https://www.cdc.gov/coronavirus/2019ncov/hcp/clinical-guidance-management-patients.html. 2. peng pwh, ho p-l, hota ss. outbreak of a new coronavirus: what anaesthetists should know. british journal of anaesthesia. 2020. 3. robert j. vissers, daniel f. danzl, serrano k. intubation and mechanical ventilation. in: hill m, editor. tintinallis emergency medicine. 2016 ed2016. p. 183-92. 4. rebelem. covid-19: the novel coronavirus 2019 2020 [cited 2020 21 march]. available from: https://rebelem.com/covid-19-the-novel-coronavirus2019/. 5. guerin c, reignier j, richard j-c, beuret p, gacouin a, boulain t, et al. prone positioning in severe acute respiratory distress syndrome. new england journal of medicine. 2013;368(23):2159-68. 6. bautista af, akca o. hypercapnia: is it protective in lung injury? med gas res. 2013;3(1):23. 7. eastwood gm, nichol a, wise mp. targeted therapeutic mild hypercapnia after cardiac arrest. critical care. 2017;21(1):196. 8. the national heart l, and blood institute acute respiratory distress syndrome (ards) clinical trials network. comparison of two fluid-management strategies in acute lung injury. new england journal of medicine. 2006;354(24):2564-75. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2020; 8 (1): e9 rev i ew art i c l e creatine phosphokinase, a new marker in diagnosis of tubal ectopic pregnancy; a systematic review maryam ghorbani1, afsaneh keramat2∗, farideh mohsenzadeh ledari3 1. student research committee, school of nursing and midwifery, shahroud university of medical sciences, shahroud, iran. 2. reproductive studies and women’s health research center, shahroud university of medical sciences, shahroud, iran. 3. infertility and health reproductive research center, health research institute, babol university of medical sciences, babol, iran. received: october 2019; accepted: december 2019; published online: 11 january 2020 abstract: introduction: creatine phosphokinase (cpk) is an intracellular enzyme found in higher levels in the brain, myocardium, soft muscle and skeletal muscle, as well as the fallopian tube. this review was conducted to evaluate the role of serum cpk in early diagnosis of tubal ectopic pregnancy (ep). methods: we performed an electronic literature search in web of science, scopus, embase and medline databases and manual search in google scholar and evaluated papers from the beginning of 1990 to september 2018. the inclusion criteria consisted of cohort, case-control and diagnostic value studies in english or persian. two independent researchers used the inclusion and exclusion criteria. in cases where there was doubt about the eligibility of studies, this problem was resolved by consulting a third researcher. after a thorough search, finally, we found 27 papers. however, four of these articles did not have the inclusion criteria and we excluded them from the study. as a result, 24 studies were evaluated. results: most studies have approved the use of cpk measurements in ep diagnosis. the main variable measured in most studies was the mean total cpk level. however, there is limited knowledge about the efficacy of measuring cpk levels in ep diagnosis; this review of studies shows positive results regarding use of cpk in ep diagnosis. conclusions: the results highlighted the potential benefits of cpk as a marker for early diagnosis of ep. keywords: pregnancy, ectopic; early diagnosis; creatine kinase; biomarkers cite this article as: ghorbani m, keramat a, mohsenzadeh ledari f. creatine phosphokinase, a new marker in diagnosis of tubal ectopic pregnancy; a systematic review. arch acad emerg med. 2020; 8(1): e9. 1. introduction ectopic pregnancy (ep) occurs when a blastocyst abnormally implants outside the endometrium of the uterus (1). it implants in the fallopian tube in more than 95% of cases (2). this disorder is a major health problem worldwide (3). the prevalence of ep has doubled since 1960 and accounts for about 2% of the pregnancies in the first trimester (1). in recent years, its incidence has increased due to the increase in incidence of pelvic inflammatory diseases, use of fertility drugs, and pelvic surgery (2). although maternal mortality due to ectopic pregnancy has decreased recently, it is still one of the leading causes of death in the first trimester of pregnancy; hence, early management of ectopic pregnancy ∗corresponding author: afsaneh keramat; 7tir street, shahroud university of medical sciences, shahroud, iran. tel: 00989125498075, e-mail: keramat2222@gmail.com is very important (3). in developing countries, such as iran, 10% of women diagnosed with ectopic pregnancy do not survive because they refer to the hospital very late (1). clinical manifestations in ectopic pregnancy can be similar to other conditions. this reveals the need to search for some new diagnostic tools. transvaginal ultrasound and serial measurement of serum beta-hcg levels are the most common diagnostic methods for ep (4). despite the use of transvaginal ultrasound and measurement of beta-hcg levels, about 40% to 50% of the initial cases of the disease are not diagnosed. transvaginal ultrasonography can help if there is an intrauterine pregnancy or an adnexal mass, and measurement of serum beta-hcg levels can detect a normal intrauterine pregnancy from a nonviable pregnancy, but it cannot differentiate an intrauterine pregnancy that has stopped growing from an ectopic pregnancy (5). creatine phosphokinase (cpk) was proposed as a new ep diagnostic criterion. lavie et al. were the first to report a sensitivity and specificity for overall cpk levels in detecting ep (2). cpk is an inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 2 tracellular enzyme found in higher levels in the brain, myocardium, soft muscle and skeletal muscle, as well as the fallopian tube (4). cpk has three definite isozymes, including cpk-mm, mb, and bb. due to the lack of a submucosal layer in the fallopian tube, the zygote implants are placed adjacent to the muscle layer in tubal ectopic pregnancy, and this invasion leads to an increase in the level of cpk as a soft muscle damage marker (2). due to the need for and importance of early detection and timely treatment of ep and the ambiguousness of ultrasound in most patients, this review is conducted to evaluate the role of serum cpk in early diagnosis of tubal ectopic pregnancy. 2. methods: in this systematic review, researchers performed an electronic search using the keywords of tubal pregnancy, ectopic pregnancy, ep, creatinine phosphokinase, and cpk in medline (via pubmed), embase, web of science, and scopus databases. manual search was also performed in google scholar to find relevant papers. we included articles published from the beginning of 1990 to september 2018. search terms were selected based on common keywords in literature. the keywords were combined using (and) and (or) operators. we used the following search strategy for finding articles with related titles and abstracts in pubmed: ((("creatine kinase"[mesh] or "creatine kinase, mb form"[mesh]) and "pregnancy, tubal"[mesh]) and "pregnancy, ectopic"[mesh]) and ("1980/01/01"[pdat]: "2018/12/31"[pdat]). 2.1. search strategy the inclusion criteria consisted of cohort, case-control and diagnostic accuracy studies in english or persian. exclusion criteria consisted of articles in languages other than english and persian, and lack of reporting the data necessary for the study. 2.2. quality control of the study two independent researchers searched the articles in accordance with inclusion and exclusion criteria. in cases where there was disagreement about the eligibility of studies, we solved the problem by consulting a third researcher. as a result, this review used 24 studies to evaluate the value of cpk in diagnosis of ep. this systematic review was reported according to prisma checklist criteria. the methodological elements of the study, including data extraction, proper sampling description, study design, participants’ characteristics, and inclusion and exclusion criteria were evaluated to ensure the quality of the selected papers. two researchers searched and extracted data independently. quadas-2 checklist was used figure 1: prisma flow diagram of the study selection process. for controlling the selected studies. this tool comprises four domains: patient selection, index test, reference standard, and flow and timing. each domain is assessed in terms of risk of bias, and the first three domains are also assessed in terms of concerns regarding applicability. signaling questions are included to help judge risk of bias. 3. results after a thorough search, we found 27 papers on cpk as a marker in diagnosis of tubal ep. however, three of these articles did not meet the inclusion criteria and we excluded them from the study for reasons including failure to report the complete information for the study, type of study, and the language of the study. as a result, 24 studies (2, 4, 6-27) were used to evaluate the value of cpk in diagnosis of ep (figure 1). 3.1. quality assessment of studies and risk of bias the risk of bias in index test, flow and timing and reference standard were low in most studies (83.3% to 91.66% of articles), but in patient selection, 29.11% of articles were high risk, 4.16% of them had unclear risk, and 66.66% had low risk. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8 (1): e9 figure 2: risk of bias and applicability graph. there were no high applicability concerns regarding patient selection, index test and reference standard among articles. figure 2 and 3 show the result of quality assessment of studies. table 1 shows the general characteristics and data of each of the articles that were included in the study. total sample size in these 24 articles was 2180 cases in different groups of patients. in all of them the control groups were normal/ intrauterine pregnancy or non-ep groups and in most of them there was also a third control group, which was abortion cases (2, 4, 9-17, 19, 21, 22, 26, 27). in a study by chandra & jain in 1995, two other control groups were also included; acute appendicitis and pelvic inflammatory disease. the result of this study showed significant difference in cpk level of ep group and these groups of patients (11). most studies have approved the use of serum cpk measurement in ep diagnosis and showed significant difference between ectopic pregnancies and intrauterine pregnancies (2, 4, 6, 7, 9-11, 16, 18, 19, 22-27) but six studies did not show any significant difference (8, 12-15, 17) . the main variable measured in most studies was the mean total cpk level, which had a wide range in these articles; ranging from 33.4 to 185.6 iu/l (table 1). reference tests for confirming ectopic pregnancy in almost all of studies were b-hcg blood sampling and/or ultrasonography. mean reported level of cpk was 95.02±51.09 iu/l for ectopic pregnancies and 53.61±19.15 iu/l for normal/intrauterine pregnancies in studies that used the same unit for reporting this biomarker (2, 4, 6, 7, 9-13, 15-18, 22-24, 27). a few studies reported the area under the receiver operating characteristic (roc) curve of cpk in this regard; birkhahn et al. (21): 0.56, ghahiri et al. (25): 0.692, soundravally et al. (4): 0.851, and shafi et al. (7): 0.864. according to these reported results, mean area under the roc curve of cpk was 0.72 in diagnosing ectopic pregnancies. studies reported different cut-points for level of cpk in diagnosis of ectopic pregnancy, ranging from 26.5 to more than 145 iu/ with sensitivity and specificity ranging from 65% to 95% and 64.5% to 100%, respectively (2,4, 6,11, 12, 16-19, 24-28). for example, lavie et al. (9), reported cpk level of 45 iu/l as a cut-point for diagnosing ep with 100% sensitivity and 100% specificity, whereas at the same cut-point, duncan et al. (10) and zorn et al. (15) reported sensitivity of 57% and 50%, and specificity of 67% and 76%, respectively. some studies, only reported the cut-point without calculating sensitivity and specificity; for example korhonen et al. (14), plewa et al. (16), and vitoratos (17), claimed that cpk=30 iu/l, cpk âl’ě 74 iu/l, cpk=145 iu/l are suitable for diagnosing ectopic pregnancy, respectively. 4. discussion the results highlighted the potential benefits of cpk as a marker for early diagnosis of ep. studies show that the reported prevalence of ep is increasing in different countries in recent decades due to improved initial diagnosis and increased risk factors for ep, especially the use of assisted reproductive technology. timely diagnosis of ep saves the mother and ensures her health. therefore, we conducted a systematic review of existing papers to investigate and introduce an applied method for early diagnosis of ep to prevent its complications and consequences. cpk is an intracellular enzyme in muscle cells and its plasma level increases in cell lysis. lysis of trophoblast cells leads to an increase in plasma cpk levels. therefore, the level of this enzyme can be used for evaluation of tubal ectopic pregnancy because increased cpk can be associated with trophoblastic invasion and trophoblast mass (6). currently, transvaginal ultrasound and serial measurement of serum beta-hcg levels are the most common diagnostic methods for ectopic pregnancy (7). if the ultrasound shows the presence of pregnancy tissue in adnexa without evidence of intrauterine pregnancy, the presence of ectopic pregnancy should be suspected (28), if the yolk sac or embryo are detected in the ep tissue, the diagnosis of ep is confirmed. serum beta-hcg also plays an important role in diagnosis of ep along with ultrasound (29). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 4 figure 3: risk of bias and applicability concerns summary. despite the widespread use of transvaginal ultrasound and beta-hcg, it is believed that 40% to 50% of ep cases remain unidentified in the early stages. despite the advances in ultrasound, according to recent reports, 48-8% of all patients with abdominal pain or vaginal bleeding in the first trimester of pregnancy have an uncertain ultrasonography with serum beta-hcg level less than 1000 iu/dl. particularly, this subgroup of patients are not properly evaluated and may benefit most from other serum markers that allow rapid diagnosis (7). according to the present review, researchers around the world are interested in using cpk as a diagnostic marker for early detection of ep. asgharnia et al. reported that determining the total cpk level could increase its diagnostic value in diagnosis of tubal ectopic pregnancy; however, the need for larger scale studies was felt to appropriately determine the cut-off point of this marker. they did not find any significant differences between study groups regarding cpk-mb levels (2). six of the papers reviewed in this study did not confirm the significance of the differences in cpk levels between those with intrauterine and ectopic pregnancies. according to the studies summarized in table 1, all of these articles, except for one published in 2012 (8), were published in the years before 2000 (12-17). kruchkovich et al. reported that no significant difference in cpk and cpk-mb levels had a diagnostic value for ep. they concluded that the inaccuracies observed regarding cpk in that study could be due to the participation of subjects with less than 7 weeks of gestational age because cpk level might also be related to the gestational age (8). plewa et al. reported that although there are higher levels of cpk in patients with ectopic pregnancy compared to those with abortion or normal pregnancy, due to a significant overlap in cpk levels, the use of this serum marker for ep diagnosis is unreliable (16). a drawback of that study was its small sample size, especially in the ep group, which can reduce the confidence in the confirmation of its findings. 4.1. the strengths and limitations of this study • this study examined various aspects of cpk and its evidence in early diagnosis of ep. • systematic reviews provide the highest level of evidence for decision-making. to the best of our knowledge, there was no systematic review for the current issue. • two independent researchers conducted screening and extraction of studies. 5. conclusion according to this review, serum cpk level can be used as a diagnostic marker for ectopic pregnancies and it seems that mean level of cpk is 95.02±51.09 iu/l for ectopic pregnancies and 53.61±19.15 iu/l for normal/intrauterine pregnancies. 6. declarations: 6.1. acknowledgements the authors thank shahroud university of medical sciences for its financial support. 6.2. authors contributions maryam ghorbani developed the original idea and the protocol, searched in different scientific websites, abstracted and analyzed data, assessed quality of articles, wrote the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8 (1): e9 manuscript and prepared the table. afsaneh keramat contributed to the development of the protocol, abstracted data, searched in different scientific websites and prepared the manuscript, assessed quality of articles and is guarantor. farideh mohsenzadeh ledari assessed quality of articles, edited grammatical and translation errors. authors orcids maryam ghorbani: 0000-0003-3946-7479 afsaneh keramat: 0000-0002-8728-7790 farideh mohsenzadeh ledari: 0000-0001-8939-3186 6.3. funding support this research was financially supported by shahroud university of medical sciences. 6.4. conflict of interest authors declare that there is no conflict of interest. references 1. saadati n, najafian m, masihi s, safiary s, abedi p. comparison of two different protocols of methotrexate therapy in medical management of ectopic pregnancy. iranian red crescent medical journal. 2015;17(12). 2. asgharnia m, faraji r, mirblouk f, roshan za, parvizi a. evaluation of serum creatine phosphokinase in diagnosis of tubal ectopic pregnancy compared with intrauterine pregnancy and threatened abortion. iranian journal of reproductive medicine. 2012;10(4):303. 3. ghelichkhani p, yousefifard m, nazemi l, safari s, hosseini m, baikpour m, et al. the value of serum îšsubunit of human chorionic gonadotropin level in prediction of treatment response to methotrexate in management of ectopic pregnancy; a systematic review and meta-analysis. international journal of pediatrics. 2016;4(9):3503-18. 4. soundravally r, latha mtk, raghavan ss, ananthanarayanan p, srilatha k. diagnostic significance of total creatine kinase and its isoform in tubal. minerva ginecol. 2010;62:49-62. 5. cabar fr, fettback pb, pereira pp, zugaib m. serum markers in the diagnosis of tubal pregnancy. clinics. 2008;63(5):701-8. 6. develioglu oh, askalli c, uncu g, samli b, daragenli o. evaluation of serum creatine kinase in ectopic pregnancy with reference to tubal status and histopathology. bjog: an international journal of obstetrics & gynaecology. 2002;109(2):121-8. 7. shafi s, beigh m, jan s. reliability of maternal serum creatine kinase in diagnosis of tubal pregnancy. 8. kruchkovich j, orvieto r, fytlovich s, lavie o, anteby ey, gemer o. the role of cpk isoenzymes in predicting extrauterine early pregnancy. archives of gynecology and obstetrics. 2012;286(1):135-7. 9. lavie o, beller u, neuman m, ben-chetrit a, gottcshalksabag s, diamant yz. maternal serum creatine kinase: a possible predictor of tubal pregnancy. american journal of obstetrics and gynecology. 1993;169(5):1149-50. 10. duncan w, sweeting v, cawood p, illingworth p. measurement of creatine kinase activity and diagnosis of ectopic pregnancy. bjog: an international journal of obstetrics & gynaecology. 1995;102(3):233-7. 11. chandra a, martinez gm, mosher wd, abma jc, jones j. fertility, family planning, and reproductive health of us women; data from the 2002 national survey of family growth. 2005. 12. darai e, vlastos g, benifla jl, sitbon d, hassid j, dehoux m, et al. is maternal serum creatine kinase actually a marker for early diagnosis of ectopic pregnancy? european journal of obstetrics & gynecology and reproductive biology. 1996;68:25-7. 13. lincoln sr, dockery jr, long ca, rock wa, cowan bd. maternal serum creatine kinase does not predict tubal pregnancy. journal of assisted reproduction and genetics. 1996;13(9):702-4. 14. korhonen j, alfthan h, stenman u-h, ylostalo p. failure of creatine kinase to predict ectopic pregnancy. fertility and sterility. 1996;65(5):922-4. 15. zorn j-r, cherruau b, abi-rached f, dehee a, danoy x, le blond j, et al. evaluation of maternal plasma creatine kinase activity as a marker of abnormal early pregnancy. human reproduction. 1997;12(11):2534-7. 16. plewa mc, ledrick d, buderer nf, king rw. serum creatine kinase is an unreliable predictor of ectopic pregnancy. academic emergency medicine. 1998;5(4):300-3. 17. vitoratos n, gregoriou o, papadias c, konidaris s, kalogirou d, kalampokis d, et al. clinical value of creatinine kinase in the diagnosis of ectopic pregnancy. gynecologic and obstetric investigation. 1998;46(2):80-3. 18. saha p, gupta i, ganguly n. evaluation of serum creatine kinase as a diagnostic marker for tubal pregnancy. australian and new zealand journal of obstetrics and gynaecology. 1999;39(3):366-7. 19. spitzer m, pinto ab, dasgupta r, benjamin f. early diagnosis of ectopic pregnancy: can we do it accurately using a biochemical profile? journal of women’s health & gender-based medicine. 2000;9(5):537-44. 20. birkhahn rh, gaeta tj, leo pj, bove jj. the utility of maternal creatine kinase in the evaluation of ectopic pregnancy. the american journal of emergency medicine. 2000;18(6):695-7. 21. birkhahn rh, gaeta tj, paraschiv d, bove jj, suzuki t, kathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 6 toh h, et al. serum levels of myoglobin, creatine phosphokinase, and smooth muscle heavy-chain myosin in patients with ectopic pregnancy. annals of emergency medicine. 2001;38(6):628-32. 22. katsikis i, rousso d, farmakiotis d, kourtis a, diamantikandarakis e, zournatzi-koiou v, et al. creatine phosphokinase in ectopic pregnancy revisited: significant diagnostic value of its mb and mm isoenzyme fractions. american journal of obstetrics and gynecology. 2006;194(1):86-91. 23. wazir s, yasmeen s, prarveen s, nisar s, parveen s, chesti s, et al. reliability of maternal serum creatinine phosphokinase (cpk) in the diagnosis of ectopic pregnancy. 2009. 24. kh e, sd s. the value of serum creatine phosphokinase for diagnosis of ectopic pregnancy. zums journal. 2013;21(86):97-104. 25. ghahiri a, moshreffar a, najafian a, ghasemi m, tehrani hg. assessment of the diagnostic capability of serum creatine phosphokinase and its isoenzyme in ectopic pregnancy. international journal of fertility & sterility. 2012;6(3):185. 26. abdullateef ha. serum creatine kinase and its isoenzyme ck-mb in the prediction of tubal ectopic pregnancy. iraqi journal of medical sciences. 2013;11(2):1705. 27. suvarna jyothi ganta srk, vidya muralidhar. cpk: the new tool in the diagnosis of ectopic pregnancy. international journal of reproduction, contraception, obstetrics and gynecology. 2017;6(6):2507-11. 28. kirk e, bottomley c, bourne t. diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location. human reproduction update. 2013;20(2):250-61. 29. van mello n, mol f, opmeer b, ankum w, barnhart k, coomarasamy a, et al. diagnostic value of serum hcg on the outcome of pregnancy of unknown location: a systematic review and meta-analysis. human reproduction update. 2012;18(6):603-17. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 1 lavie et al. (9)1993 mean age of participants: not reported mean gestational age: not reported total sample size: 51 groups of study: 3 groups of women: tubal pregnancy (n=17) missed abortion (n=17) normal pregnancy (n=17) method of measuring cpk: reflectance spectrophotometry of chromophore production. time of sampling: on admission reference test to confirm ectopic pregnancy: physical examination, ultrasonographic examination, and routine blood tests mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 78.125 ± 6.369 mean level(±sd) of cpk in intra uterine pregnancies(iu/l): 31.125 ± 2.213 mean level(±sd) of cpk in missed abortions(iu/l): 26 .25 ± 6.149 p-value: p < 0.0001 (sig1 ) cut-point 45 iu/l sensitivity: 100% specificity: 100% 2 duncan et al. (10) 1995 mean age of participants: not reported mean gestational age: not reported total sample size: 120 groups of study: 4 groups of patient: ep (n=21), complete miscarriage (n=47), incomplete miscarriage (n=32), ongoing pregnancies (n=20). method of measuring cpk: hitachi discrete analyzer time of sampling: on admission reference test to confirm ectopic pregnancy: initial clinical assessment and plasma hcg concentration, laparoscopy or laparotomy, histological assessment. mean level of cpk in intact ectopic pregnancy(iu/l): 53.4 mean level of cpk in complete miscarriage: 37.7 mean level of cpk in intra uterine pregnancy(iu/l): 42 p –value: p < 0.001 (sig) cut-point: 45 iu/l sensitivity : 0.57 specificity : 0.67 3 chandra & jain (11) 1995 mean age of participants: not reported mean gestational age: 6-8 weeks total sample size: 90 groups of study: 5 groups of patients; normal pregnancy (n=20), missed abortion(n=20), tubal pregnancy (n=20), acute appendicitis (n=10) pelvic inflammatory disease (n=20). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 8 table 1: characteristics of studies included in the review no 1st author, year of publication research information 3 method of measuring cpk: beckman cx5 synchron (brea, ca) fully automated clinical chemistry analyzer. time of sampling: before any surgical intervention reference test to confirm ectopic pregnancy: physical examinations were carried out along with routine blood tests and ultrasonographic examination. mean level (±sd) of cpk in intact ectopic pregnancy(iu/l): 126±51.78 mean level(±sd) of cpk in missed abortion: 41±9.7 mean level(±sd) of cpk in pelvic inflammatory disease: 46±9.7 mean level(±sd) of cpk in acute appendicitis: 52±14.38 mean level(±sd) of cpk in normal pregnancy: 42±9.34 p-value: p < 0.0001, (sig). 4 darai et al. (12) 1996 mean age of participants: not reported mean gestational age in ep: 47.6 days mean gestational age in ongoing pregnancy: 49.3 days mean gestational age in missed abortion: 48.7 days no statistically significant difference in ga was found between the 3 groups. total sample size: 90 groups of study: 3 groups of women: tubal pregnancy (n=30) ongoing pregnancy(n=30), spontaneous miscarriage(n=30) method of measuring cpk: multiparametric analyser (hitachi 737) with ck nacetyl cysteine reagents (boehringer mannheim uk ltd, leves, uk) time of sampling: before any surgical intervention reference test to confirm ectopic pregnancy: progesterone, beta-hcg, pelvic sonography mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 81.4±66.2 iu/l mean level(±sd) in missed abortions (iu/l): 84.8±49.3 mean level(±sd) of cpk in ongoing pregnancies(iu/l): 81.5±40.3 p-value: not reported there was no statistically significant difference in these 3 groups. (ns2 ) there was no significant difference in ck level between patients with rupture of tubal wall and patients without rupture. (ns) there was not any difference in ckmb level between 3 groups of patients. (ns) 5 lincoln et al. (13) 1996 mean age of participants: not reported mean gestational age: first-trimester total sample size: 51 groups of study: 3 groups of patients: spontaneous abortion (n=16), ep (n=18) ongoing pregnancy (n=17) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 5 lincoln et al. (13) 1996 method of measuring cpk: ektachem 700 discrete analyzer (eastman kodak co., rochester, ny). time of sampling: on admission reference test to confirm ectopic pregnancy: quantitative hcg level, transvaginal sonography and surgery. mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 90.6±15.9 mean level(±sd)of cpk in ongoing pregnancies(iu/l): 78±13.8 mean level(±sd)of cpk in abortions(iu/l): 94.1±13 p-value: p>0.7 (ns) auc3 : 0.501 ± 0.007. p-value: p > 0.05, (ns). 6 korhonen et al. (14) 1996 mean age of participants: not reported mean gestational age in ep group: 44.9 ± 9.9 days mean gestational age in normal pregnancy group; 37.5 ± 4.0 total sample size: 44 method of measuring cpk: hitachi 911 discrete analyzer using ck n-acetyl cysteine activation reagents at 37◦c time of sampling: on admission or after repeated examinations groups of study: 3 groups of patients: spontaneous abortion, blighted ovum, or missed abortion (n=15) tubal pregnancy (n=15) normal intrauterine pregnancy (n=14). reference test to confirm ectopic pregnancy: transvaginal sonography, laparoscopy and serum hcg mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): not reported mean level (±sd) of cpk in intra uterine pregnancies(iu/l): not reported mean level (±sd) of cpk in missed abortions(iu/l): not reported p-value: not reported no significant differences in ck levels were observed between the groups. (ns) cut-point: 30 iu/l p-value: p < 0.005, (sig.) sensitivity: not reported specificity: not reported this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 10 table 1: characteristics of studies included in the review no 1st author, year of publication research information 7 zorn et al. (15) 1997 mean age of participants: not reported mean gestational age: not reported total sample size: 57 groups of study: 3 groups of patients: normal pregnancy (n=20), miscarriage (n=23), ep (n=14). method of measuring cpk: hitachi 717 analyzer time of sampling: on admission reference test to confirm ectopic pregnancy: b-hcg mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 44.2±3.6 mean level(±sd) of cpk in intra uterine pregnancies(iu/l): 36.8±5.1 mean level(±sd) of cpk in intra miscarriages(iu/l): 51.7±7.2 p-value: not reported there was no significant difference between either normals and miscarriages or miscarriages and ectopics. cut-point: > 45 iu/l p-value: p < 0.02 (sig) sensitivity: 0.50 specificity: 0.76 ppv: 0.69 8 plewa et al. (16) 1998 mean age of participants: not reported mean gestational age in participants: 7.3± 2.3 weeks total sample size: 64 groups of study: 3 groups of patients: ep (n=15) threatened miscarriage (n=28) normal pregnancy (n=21). method of sampling cpk: ck was spectrophotometrically assayed with standard reagents by an enzymatic rate method on a synchron cx system time of sampling: initial presentation reference test to confirm ectopic pregnancy: quantitative betahcg laparoscopy, ultrasonography, dilatation and curettage mean level (±sd) of cpk in intact ectopic pregnancy(iu/l): 88.8±33.6 mean level (±sd) of cpk in intra uterine pregnancy(iu/l): 56±38.1 mean level (±sd) of cpk threatened miscarriage (iu/l): 65.9±59 p-value: p=0.02, (sig) cut-point. ≥ 74 iu/l sensitivity: not reported specificity: not reported this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 9 vitoratos et al. (17) 1998 mean age of participants: not reported mean gestational age: not reported total sample size: 66 groups of study: 3 groups of patients; ep (n=21), normal pregnancies (n=20), abortion (n=15). method of measuring cpk: not reported time of sampling: not reported reference test to confirm ectopic pregnancy: beta-hcg, sonography mean level (±sd) of cpk in asymptomatic ectopic pregnancies(u/l): 58.5 ± 12.42 mean level (±sd)of cpk in symptomatic ectopic pregnancies(u/l): 59 ±10.08 p-value: p = 0.45, (ns) 1.mean level (±sd) of cpk in normal pregnancies (u/l): 58.5 ± 7.24 2.mean level (±sd) of cpk in threatened abortion (u/l): 73 ± 11.43 cut-point: 145 iu/l sensitivity: not reported specificity: not reported 10 saha et al. (18) 1999 mean age of participants: not reported mean gestational age: not reported total sample size: 40 groups of study: 2 groups of patients: ep (n=20), normal pregnancy (n=20). method of sampling cpk: kontron-890 spectrophotometer time of sampling: before any invasive procedure reference test to confirm ectopic pregnancy: physical examination, routine blood test, ultrasonographic examination and urine pregnancy test. mean level (±sd) of cpk in intact ectopic pregnancy(iu/l): 34.15± 1.17 mean level (±sd) of cpk in intra uterine pregnancy(iu/l): 18.72 ± 1.25 p-value: p< 0.001, (sig) cut-point: not-reported sensitivity: not reported specificity: not reported 11 spitzer et al. (19) 2000 mean age of participants: not reported mean gestational age: first trimester total sample size: 65 groups of study: 3 groups of patients: ep (n=23), normal pregnancy (n=21), abnormal pregnancy (n=21). method of sampling cpk: hitachi discrete analyzer using creatine ki-nase nacetyl cysteine activation reagents at 37 time of sampling: on admission reference test to confirm ectopic pregnancy: transvaginal ultrasound examination and blood sample for evaluating progesterone, 17hydroxyprogesterone, ca-125 and androstenedione this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 12 table 1: characteristics of studies included in the review no 1st author, year of publication research information 11 spitzer et al. (19) 2000 mean age of participants: not reported result in patients with 45days of amenorrhea: mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 88.6/96.3± 37.4 mean level (±sd) of cpk in normal pregnancies(iu/l): 54/54.1 ± 170 mean level (±sd) of cpk in abnormal pregnancies(iu/l): 77/78.1 ± 46.4 p-value: p < 0.002 result in patients with 2500 miu/ml b-hcg: mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 84.5/88.1± 31.8 mean level (±sd) of cpk in normal pregnancies(iu/l): 30.6 mean level (±sd) of cpk in abnormal pregnancies(iu/l): 61/62.5± 24.7 cut-point: p>0.50 iu/l sensitivity: 94% specificity: 31% cut-point: p>0.70 iu/l sensitivity : 78% specificity: 81% 12 birkhahn* et al. (20) 2000 mean age of participants in non ep group: 29.4±6.1 *in this article different unit (miu/dl) mean gestational age: first trimester has been used for measuring cpk mean age of participants in ep group: 31.2±5.8 total sample size: 42 groups of study: 2 groups of patients: ep (n=21), non-ep (n=21). method of measuring cpk: not reported time of sampling: at the time of presentation reference test to confirm ectopic pregnancy: ultrasonography, laparoscopy, or laparotomy. mean level (±sd) of cpk in intact ectopic pregnancies (miu/dl): 118±47 mean level (±sd) of cpk in noneps (miu/dl): 64±45.3 p-value: p < .0031, (sig) cut-point: 70 miu/dl sensitivity: 100% specificity: 61.9% ppv: 72.4% npv: 100% 13 birkhahn* et al. (21) 2001 mean age of participants in ep group: 31.9 *in this article different unit (ng/dl) mean age of participants in non-ep group: 27.8 has been used for measuring of cpk mean gestational age: first trimester total sample size: 378 groups of study: 2 groups of patients: patients at less than 5 weeks’ gestation and ep(n=61: ruptured=24 or unruptured=37), non-ectopic pregnancy(n=317; spontaneous abortion, threatened, incomplete, missed, and complete, urinary tract infection, corpus luteal cyst, nonspecific abdominal pain, renal cyst, pelvic inflammatory disease, or appendicitis ). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 13 method of measuring cpk: opera, bayer corporation, pittsburgh, pa time of sampling: at the time of presentation reference test to confirm ectopic pregnancy: surgical pathology reports or ultrasonographic scans, β-hcg, smhc4 and myoglobin test. mean level (95% ci) of cpk in ectopic pregnancies (ng/dl): 119 (89–149) mean level (95% ci) of cpk in unruptured ectopic pregnancies (ng/dl): 104 (85–122) mean level (95% ci) of cpk in ruptured ectopic pregnancies (ng/dl): 139 (66–212) mean level (95% ci) of cpk in non-ectopic pregnancies (ng/dl): 105 (95–115) p-value: not reported the auc for total creatine kinase: 0.56 (95% ci0.51 to 0.61) cut-point: 1.1 µg/l sensitivity: 72% specificity: 52% the auc for smhc: 0.63 14 develioglu et al. (6) 2002 mean age of participants in isthmic ep group: 34±3.3 mean age of participants in ampullary ep group: 31.5±5.1 mean gestational age in isthmic ep: 35.8±3.7 days mean gestational age in ampullary ep: 37.6±5 days total sample size: 52 groups of study: 2 groups of patients: ep (n=32), intrauterine pregnancies (n=20). method of measuring cpk: spectrophotometric method on a technicon dax systems automated analyzer time of sampling: on admission reference test: beta-hcg, ultrasound, endometrial biopsy, laparoscopy or laparotomy. mean level (±sd) of cpk in in isthmic ep(iu/l): 185.6±58.3 mean level (±sd) of cpk in in ampullary ep(iu/l): 112.3±55.5 p-value: p=0.011, (sig) mean level (±sd) of cpk in in ruptured ep(iu/l): 152.1±61.2 mean level (±sd) of cpk in in unruptured ep(iu/l): 91.6±44.3 mean ck level in normal pregnancy (iu/l): 77.4±38.2 p-value: p<0.011, (sig) comparing cpk levels in isthmic and ampullary ectopic pregnancies. p<0.003, (sig) comparing cpk levels in ruptured ectopic pregnancy and unruptured p<0.0001, (sig). comparing cpk levels in unruptured ectopic pregnancy and normal pregnancy. cut-point: >120 iu/l sensitivity: 65% specificity: 87% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 14 table 1: characteristics of studies included in the review no 1st author, year of publication research information 15 katsikis et al. (22) 2006 mean age of participants in ep group: 28.1±6.3 mean age of participants in abortion group: 26.9±4.9 mean age of participants in normal pregnancy: 24.6±2.7 mean gestational age: first trimester total sample size: 80 groups of study: 3 groups of patients: ep (n=40), abortion (n=20), normal intrauterine pregnancy (n=20). method of measuring cpk: enzyme-linked immunoassay (elisa) time of sampling: at the time of presentation and 24 hours after surgery in the subgroups of women with ep and intra uterine abortion reference test to confirm ectopic pregnancy: clinical assessment and transvaginal ultrasonography, beta-hcg mean level (±sd) of cpk in ectopic pregnancies (u/l): 33.4±15.4 mean level (±sd)of cpk in normal pregnancies (u/l): 24.7±5.7 mean level (±sd)of cpk in abortions (u/l): 17.9±3.7 p-value of comparing cpk in ep with both iu abortions: p<0.001, (sig). p-value of comparing cpk in ep with normal gestations: p<0.01, (sig). p-value of comparing cpk-mb in normal p<0.01, (sig). pregnancy compared with ep or iu abortion: cut-point: >26.5 u/l sensitivity: 80% specificity: 87.5% ppv: 86.5% npv: 81.4% cut-point: < 14.4 u/l sensitivity: 82.5% specificity: 95% ppv: 94.3% npv: 84% 16 wazir et al. (23) 2009 mean age of participants: not reported mean gestational age: first trimester total sample size: 100 groups of study: 2 groups of patients: tubal pregnancy (n=50), intra uterine pregnancy (n=50). method of measuring cpk: not reported time of sampling: on admission reference test to confirm ectopic pregnancy: physical examination, routine investigations and ultrasonography of abdomen, transvaginal ultrasound, laparoscopy and/ or laparotomy mean level (±sd) of cpk in ectopic pregnancies(iu/l): 103±50 mean level (±sd) of cpk in normal pregnancies(iu/l): 52.4 ±10.9 p-value: p=0.000, (sig). mean level (±sd) of cpk in ruptured ectopic pregnancies(iu/l): 119.8±70.5 mean level (±sd) of cpk in unruptured ectopic pregnancies(iu/l): 88.6±19.6 p-value: p=0.002, (sig). cut-point: 70 iu/l sensitivity: 95% specificity: 98% ppv: 99% npv: 90.7% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 17 elmizadeh et al. (24) 2012 mean age of participants in ep group: 27.4±6.1 mean age of participants in intrauterine pregnancy: 26.4±6.5 mean gestational age in ep group: 7.9±1.8 weeks mean gestational age in intrauterine pregnancy: 8.5±1.7 total sample size: 55 groups of study: 2 groups of patients: ep (26), normal intrauterine pregnancy (29). method of measuring cpk: kinetic uv-method time of sampling: before any invasive intervention reference test to confirm ectopic pregnancy: not reported mean level (±sd) of cpk in tubal ectopic pregnancies(iu/l): 156±93.6 mean level (±sd)of cpk in intra uterine pregnancies(iu/l): 58.63±31.5 p-value: pëć0.0001, (sig). mean level (±sd) of cpk in intact ectopic pregnancy(iu/l): 104.3±21.4 mean level (±sd) of cpk in ruptured ectopic pregnancy(iu/l): 220.8±100.5 p-value: p=0.002, (sig). sensitivity: 92% specificity: 86% ppv: 85.7% npv: 92.5% 18 asgharnia et al. (2) 2012 mean age of participants: 16-40 mean gestational age: first-trimester total sample size: 111 groups of study: 3 groups of study; tubal ectopic pregnancy (n=37) threatened abortion (n=37) normal intra-uterine pregnancy (n=37). method for measuring cpk: photometric pars-azmun kit at 37oc time of sampling: before any invasive procedure reference test to confirm ectopic pregnancy: sonography and β-hcg level mean level (±sd) of cpk in intact ectopic pregnancies (iu/l): 96.27±63.9 mean level (±sd) of cpk in normal pregnancies (iu/l): 48.94±19.2 mean level (±sd) of cpk in threatened abortions (iu/l): 55.37±14.1 p-value: p<0.0001, (sig). mean level (±sd) of cpk-mb in ectopic pregnancies (iu/l): 15.62±5.2 mean level (±sd) of cpk-mb in threatened abortions (iu/l) : 17.32±6.9 mean level (±sd) of cpk-mb in normal pregnancies (iu/l): 15.1±4.7 p-value: p=0.219, (ns). sensitivity: not reported specificity: not reported 19 kruchkovich et al. (8) 2012 mean age of participants: 29.2 years mean gestational age: 5.6 weeks total sample size: 79 groups of study: 2 groups of patients; ep (n=51) normal pregnancy (n=28). method for measuring cpk: kinetic uv test time of sampling: on admission reference test to confirm ectopic pregnancy vaginal ultrasound and serial beta hcg testing. mean level (±sd) of cpk in intact ectopic pregnancies(u/l): 80.90±62.13 mean level(±sd) of cpk in intra uterine pregnancies (u/l): 74.9±51.6 p-value: p=0.66, (ns). mean level (±sd) of cpk-mb in intact ectopic pregnancies(u/l): 11.1 ± 8.2 mean level (±sd) of cpk-mb in intra uterine pregnancies (u/l): 74.9±51.6 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 16 table 1: characteristics of studies included in the review no 1st author, year of publication research information 19 kruchkovich et al. (8) 2012 mean age of participants: 29.2 years p-value: 0.39 sensitivity: not reported specificity: not reported 20 ghahiri et al. (25) 2012 mean age of participants of ep group: 28.62 ± 4.97 mean age of participants of non-ep group: 27.58 ± 4.53 mean gestational age: first trimester total sample size: 106 groups of study: 2 groups of patients; ep (n=53), non-ep (n=53). method of measuring cpk: not reported time of sampling: on admission reference test to confirm ectopic pregnancy: transvaginal sonography, beta-hcg mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): not reported mean level (±sd) of cpk in non-ectopic pregnancies(iu/l): there not reported p-value of cpk level and the type of pregnancy: p=0.0001, (sig). p-value of cpk-mb level and the type of pregnancy: p=0.003, (sig). mean gestational age: first trimester total sample size: 106 groups of study: 2 groups of patients; ep (n=53), non-ep (n=53). method of measuring cpk: not reported time of sampling: on admission reference test to confirm ectopic pregnancy: transvaginal sonography, beta-hcg mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): not reported mean level (±sd) of cpk in non-ectopic pregnancies(iu/l): there not reported p-value of cpk level and the type of pregnancy: p=0.0001, (sig). cut-point: 61 iu/l sensitivity: 69.81% specificity: 64.15% ppv: 66.07% npv: 68% plr5 : 1.95 nlr6 : 0.49 p-value: 0.0001, (sig). auc: 0.692 cut-point for cpk-mb: 15.6 iu/l sensitivity: 71.7% specificity: 56.6% ppv: 62.29% npv: 66.7% plr : 1.65 nlr : 0.5 auc: 0.647 21 soundravally et al. (4) 2013 mean age of participants in abortion group: 24.2±4 mean gestational age in normal pregnancy: 5.4±2.1 weeks mean gestational age in abortion: 5.2±1.2 weeks mean gestational age in ep: 4.6±1.5 weeks total sample size: 63 groups of study: 2 groups of patients; ruptured ep (n=32), intrauterine abortion and normal pregnancies (n=31). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2020; 8 (1): e9 table 1: characteristics of studies included in the review no 1st author, year of publication research information 21 soundravally et al. (4) 2013 mean age of participants in abortion group: 24.2±4 method of measuring cpk: immuno-inhibition method, in an auto-mated analyzer time of sampling: at the time of presentation prior to surgical intervention reference test to confirm ectopic pregnancy: clinical assessment, beta-hcg and transvaginal ultrasonography. mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 305±357 mean level (±sd)of cpk in normal pregnancies(iu/l): 93±35 mean level (±sd) of cpk in abortions (iu/l): 87±71 p-value: p< 0.05, (sig). mean level (±sd) of cpk-mb% in intact ectopic pregnancies: 6±8 mean level (±sd)of cpk-mb% in normal pregnancies: 14±6 mean level (±sd) of cpk-mb% in abortions: 19±15 p-value: p< 0.05, (sig). cut-point for cpk: 147 iu/l sensitivity: 72% specificity: 89% cut-point for cpk-mm and cpk-mb% respectively: 132 iu/l, 10 auc: 0.882 sensitivity: 72% specificity: 93% auc: 0.851 sensitivity: 88% specificity: 68% 22 abdullateef (26) 2013 mean age of participants in ep group: 28.97±0.957 mean age of participants in abortion group: 32.05±1.95 mean age of participants in normal pregnancy: 25.8±1.139 mean gestational age: not reported total sample size: 81 groups of study: 3 groups of patients; ep (n=40), intrauterine abortion (n=17), normal pregnancy (n=24). method of measuring cpk: spectrophotometric analysis time of sampling: on admission reference test to confirm ectopic pregnancy: clinical assessment and transvaginal ultrasonography. mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): not reported mean level (±sd) of cpk in intra uterine pregnancies(iu/l): not reported mean level (±sd) of cpk in abortions(iu/l): not reported auc: 0.903 (95%ci: 0.831–0.975) p-value: p< 0.001, (sig). cut-point for cpk: 29.43 iu/l sensitivity: 92% specificity: 100% ppv: 100% npv: 96% cut-point for cpk-mb: 4.55 iu/l sensitivity: 81.64% specificity: 84.3% ppv: 71.4% npv: 71.4% this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. ghorbani et al. 18 table 1: characteristics of studies included in the review no 1st author, year of publication research information 23 shafi et al. (7) 2016 mean age of participants: not reported mean gestational age: not reported total sample size: 175 groups of study: 2 groups of patients; ep (n=100), normal pregnancy (n=75). method of measuring cpk: uv kinetic method-nac time of sampling: before any invasive procedure. reference test to confirm ectopic pregnancy: routine investigations and ultrasonography mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 97.64±33.08 mean level (±sd) of cpk in normal pregnancies(iu/l): 53.20±9.75 mean level (±sd) of cpk in ruptured tubal pregnancies(iu/l): 111.71±41.56 mean level (±sd) of cpk in unruptured tubal pregnancies(iu/l): 84.12±11.36 p-value: pëć0.001, (sig). auc: 86.4% sensitivity: not reported specificity: not reported 24 ganta et al. (27) 2017 mean age of participants: 20-40 mean gestational age: not reported total sample size: 120 groups of study: 3 groups of patients; ep (n=40), abortion (40), normal pregnancy (n=40). method of measuring cpk: nac activated with beckman coulter au480. time of sampling: before any invasive procedure reference test to confirm ectopic pregnancy: beta-hcg, sonography, laparoscopy , laparotomy mean level (±sd) of cpk in intact ectopic pregnancies(iu/l): 91.55±30.43 mean level (±sd) of cpk in ruptured ectopic pregnancies(iu/l): 97.26±25.97 mean level (±sd) of cpk in unruptured ectopic pregnancies(iu/l): 63.82±34.9 mean level (±sd) of cpk in normal pregnancies(iu/l): 36.92±6.44 mean level (±sd) of cpk in abortions(iu/l): 43.95±11.96 p-value of between 3 groups: p<0.0001, (sig). p-value of ruptured and unruptured ep: p=0.015, (sig). sensitivity: not reported specificity: not reported 1. significant 2. not significant. 3. area under the receiver operating characteristic (roc) curve 3. area under the receiver operating characteristic (roc) curve 4. smooth muscle heavy-chain myosin 5. positive likelihood ratio 6. negative likelihood ratio sd: standard deviation; ck/cpk: creatine phosphokinase; ep: ectopic pregnancy; sig: significant; ppv: positive predictive value; ns: not significant; auc: area under the receiver operating characteristic (roc) curve; npv: negative predictive value; ga: gestational age; smhc: smooth muscle heavy-chain myosin; plr: positive likelihood ratio; nlr: negative likelihood ratio; nac: n-acetyl-cystein. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods: results discussion conclusion declarations: references archives of academic emergency medicine. 2019; 7 (1): e56 or i g i n a l re s e a rc h validation of suspekt score in predicting one-month mortality of patients with hemorrhagic stroke; a diagnostic accuracy study hamid kariman1, hamidreza hatamabadi1, majid shojaee1, farhad asarzadegan2, simin saljughi1∗ 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. neurology department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: july 2019; accepted: august 2019; published online: 29 september 2019 abstract: introduction: predicting the outcome of patients with intracranial hemorrhage (ich) is the area of interest for in charge physicians as well as patients and their associates. this study aimed to evaluate the accuracy of suspekt score in predicting one-month outcome of patients with hemorrhagic stroke. methods: this prospective cross sectional study was conducted on > 18 years old patients with non-traumatic supra-tentorial ich admitted to emergency department, from february 2017 to january 2018. suspekt score was measured for each patient and its screening performance characteristics in prediction of one-month mortality were calculated. results: 169 cases with the mean age of 63.09 ± 15.45 (21 – 96) years were studied (56.8% male). after one month follow up 47 (27.8%) cases had died, 30 (17.7%) cases were bed ridden, and 72 (42.6%) could walk without help or with a cane. non-survived patients had significantly larger intra-ventricular hemorrhage (ivh) (p < 0.001) and hematoma (p < 0.001) volume, higher serum glucose (p < 0.001) and blood pressure (p = 0.028), higher frequency of ivh (p < 0.001), and higher wbc count (p = 0.037). sensitivity, specificity, positive predictive value (ppv ), and negative predictive value (npv ) of suspekt score at the 65 cut point were 82.97% (95% ci: 68.65% – 91.86%), 74.59% (95% ci: 65.76% – 81.84%), 55.71% (95% ci: 43.38% – 67.40%), and 91.91% (95% ci: 84.23% – 96.16%), respectively. conclusion: total accuracy of suspekt score in predicting one-month mortality of nontraumatic ich patients is in good range and it has 82% sensitivity and 92% npv in this regard. it seems that we need further studies before applying the score in routine practice. keywords: intracranial hemorrhages; stroke; decision support techniques; prognosis; patient outcome assessment; mortality cite this article as: kariman h, hatamabadi h, shojaee m, asarzadegan f, saljughi s. validation of suspekt score in predicting one-month mortality of patients with hemorrhagic stroke; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e56. 1. introduction intracranial hemorrhage (ich) is accountable for 15% of all strokes but it is one of the most disabling forms of stroke (1). spontaneous non-traumatic ich is associated with high mortality rate worldwide (2). more than thirty percent of patients with ich will not survive and only 20% of them will go on to be functional and live independently (3). the global burden of disease 2010 study showed a 47% increase in the absolute number of hemorrhagic strokes throughout the world during 1990-2010. the largest proportion of ich ∗corresponding author: simin saljughi; imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. email: siminsaljughi@gmail.com, tel: 00989125705371 incident cases (80%) and deaths (63%) occurred in lowand middle-income countries such as sub-saharan africa, central asia and southeast asia (4). mortality of ich is estimated as forty percent in one month and 54% in one year (5). therefore, outcome prediction of these patients is the area of interest for in charge physicians as well as patients and their associates. predicting stroke outcomes is widely studied, and a lot of factors such as age, glasgow coma scale, hematoma volume and location, and presence of intra-ventricular hemorrhage (ivh) are introduced and discussed as the risk factors of mortality in these patients (6-8). despite previous investigations, there is no validated clinical scoring system for wide use in predicting the prognosis of ich patients. in a recent study, suspekt score was proposed as a simple, cheap and reproducible scoring system for 30-day clinical outcome this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. kariman et al. 2 prognosis in ich patients. this score consists of six parameters: serum glucose, total hematoma volume, systolic blood pressure, existence of intra-ventricular hemorrhage, serum potassium level, and age (9). this study aimed to evaluate the accuracy of the mentioned clinical rule in predicting one-month mortality of ich patients referred to emergency department. 2. methods 2.1. study design and setting this prospective cross sectional study was conducted on patients with primary non-traumatic ich admitted to imam hossein hospital, tehran, iran, from february 2017 to january 2018. suspekt score was measured for each patient and its accuracy in prediction of one-month mortality was calculated. the study protocol was approved by ethics committee of shahid beheshti university of medical sciences (ethics code: ir.smbu.retech.rec.1395.295). an informed consent form was completed by participants or their legal guardian. patients had the right to decline to continue in every stage the study. 2.2. participants hemorrhagic stroke patients over 18 years old who were admitted to emergency department within 24 hours after the stroke were included. patients with unstable hemodynamic status, pregnancy/ breastfeeding, previous neurologic deficit, sub-arachnoid hemorrhage (sah), infra-tentorial hemorrhage, arteriovenous malformations, and history of brain tumor, as well as those who underwent neurosurgical evacuation or drainage, and had incomplete data were excluded. all patients were transported to our emergency department within 24 hours of stroke onset. if this point of time could not be ascertained, we used the last time when the patient was known to be well. 2.3. data gathering a researcher-made checklist was completed for each patient, which consisted of age, gender, history of smoking and alcohol usage, as well as systolic and diastolic blood pressure at the time of admission to emergency department. we also recorded laboratory data of patients including serum potassium, hemoglobin, serum glucose, white blood cell (wbc) and platelet counts. a senior emergency medicine resident was responsible for data gathering under the direct supervision of an emergency medicine specialist. 2.4. outcome the main outcome was one-month mortality. we also categorized patients in five outcome categories as dead, walking without help, walking with help, bedridden and wheel-chair dependent. 2.5. procedure after providing critical care and monitoring, all patients underwent brain computed tomography (ct) scan without contrast within 30 minutes of arrival, and if ich was confirmed via ct scan the patient was evaluated for eligibility. two consultant radiologists, who were blinded to the outcome, performed image analysis, independently. brain ct scans were performed on 16-slice multi-detector ct scanners. slice thickness was 5 to 10 mms for supra-tentorial and 2.5 to 4 mms for infra-tentorial regions. images were transferred to an offline image processing workstation as dicom (digital imaging and communications in medicine) files. radiologists separated intracranial space from the skull and non-brain structures for analysis. the following variables were evaluated: total intracranial volume; total hematoma volume; intra-parenchymal hematoma volume; and intra-ventricular hematoma volume, each expressed as cm3. additionally, relative volumes were defined as the ratio of total, intra-parenchymal, and intra-ventricular hematoma volumes to intra-cranial volume yielding variables (without unit). 2.6. suspekt score we calculated suspekt score according to the previously published article by rita szepesi and colleagues in 2014 (9). this score is developed to predict the 30-day mortality of ich patients using 6 factors including serum glucose, total hematoma volume, systolic blood pressure, presence of ivh, serum potassium level, and age. 2.7. statistical analysis the sample size, considering α = 0.05, standard deviation = 3.5, d = 7.4, and power = 80%, was calculated to be 170 cases. the data were analyzed using spss version 21 statistical software. mean ± standard deviation or frequency and percent were used for descriptive statistics. for comparison of the findings between groups, we used t-test and chi square test. the screening performance characteristics (sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr), and negative likelihood ratio (nlr)) of suspekt score in prediction of one-month mortality was calculated using vassarstats medical calculator with 95% confidence intervals (ci). total accuracy and the best cut point of suspekt in this regard were calculated using the area under the receiver operating characteristic (roc) curve. accuracy of 0.90-0.100 was considered as excellent, 0.80-0.90 as good, 0.70-0.80 as fair, 0.600.70 as poor, and 0.50-.60 as fail. p value less than 0.05 was considered significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e56 table 1: baseline characteristics of participants variable value age (year) 20-39 13 (7.7) 40-59 49 (29.0) >60 107 (63.3) gender male 96 (56.8) female 73 (43.2) history smoking 19 (11.2) alcohol abuse 75 (44.4) blood pressure (mmhg) systolic 159.10 ± 34.95 diastolic 80.22 ± 16.98 blood glucose level (mmol/l) mean ± sd 8.80± 4.29 laboratory parameters serum potassium (meq/l) 3.99 ± 0.53 hemoglobin (mg/dl) 13.24 ± 1.90 platelet count (109 cells /liter) 234.18 ± 74.95 wbc count (109 cells/liter) 9.60 ± 3.21 ivh size (cm3 ) mean ± sd 0.010 ± 0.026 total hematoma size (cm3 ) mean ± sd 0.039 ± 0.048 data are presented as mean ± standard deviation (sd) or frequency (%). wbc: white blood cell; ivh: intraventricular hematoma. 3. results 3.1. baseline characteristics of participants 169 cases with the mean age of 63.09 ± 15.45 (21 – 96) years were studied (56.8% male). the baseline characteristics of patients are listed in table1. more than 90% of cases were in > 40 years range. the mean ivh and total hematoma size in this series were 0.010 ± 0.026 cm3 and 0.039 ± 0.048 cm3, respectively. after one month follow up 47 (27.8%) cases had died, 30 (17.7%) cases were bed ridden, and 72 (42.6%) could walk without help or with a cane. table 2 compares the baseline characteristics of survived and non-survived cases. nonsurvived patients had significantly larger ivh (p < 0.001) and hematoma (p < 0.001) volume, higher blood glucose level (p < 0.001) and blood pressure (p = 0.028), and higher wbc count (p = 0.037). 72.3% (34 cases) of non-survived patients had ivh, while only 15.6% (19 cases) of survived cases had simultaneous ventricular hemorrhage (p < 0.001). 3.2. accuracy of suspekt score the mean suspekt score of non-survived patients was significantly higher than survived cases (78.51 ± 22.64 vs 48.85 ± 28.3; p < 0.0001). the area under the roc curve of suspekt score in prediction of one-month mortality of ich patients was 0.803 (95% ci: 0.727-0.879; p<0.001). the best cut point figure 1: area under the receiver operating characteristic (roc) curve of suspekt score in predicting one-month mortality of patients with intracranial hemorrhage. for the score in this regard was 65 (based on roc curve). sensitivity, specificity, ppv, npv, plr, and nlr of suspekt score at the 65 cut point were 82.97% (95% ci: 68.65% – 91.86%), 74.59% (95% ci: 65.76% – 81.84%), 55.71% (95% ci: 43.38% – 67.40%), 91.91% (95% ci: 84.23% – 96.16%), 1.25 (95% ci: 0.89 – 1.75), and 0.09 (95% ci: 0.05 – 0.17), respectively. 4. discussion based on the findings of the present study, the total accuracy of suspekt score in predicting one-month mortality of ich patients is in good range and it has 82% sensitivity and 92% npv in this regard. despite wide researches performed on predicting mortality of primary ich cases, there is no reliable and widely used scoring system in this regard (6, 10, 11). there are different prognostic models in predicting mortality of ich (12, 13). these studies have been focused on age, low level of consciousness, location or volume of hemorrhage, existence of hydrocephalus in ct scan, and focal neurologic symptoms on admission as possible prognostic factors of outcome (14-17). tsikriki et al., in their study regarding the prognostic factors of mortality following ich, demonstrated the independent association of apache ii score, sofa score, gcs on admission, and ich volume with 30-day mortality (18). in line with szepesi et al. study, we showed that each item of suspekt score, except for two variables of age and serum potassium level, significantly correlated with the 30-day outcome of ich patients, independently (9). it is shown that serum this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. kariman et al. 4 table 2: comparing the baseline characteristics of survived and non-survived cases variable survived (n=122) dead (n= 47) p gender female 52 (42.6) 21 (44.7) 0.47 male 70 (57.4) 26 (55.3) age (year) mean ± sd 62.04 ± 15.60 65.83 ± 14.78 0.81 serum potassium (meq/l) mean ± sd 4.00 ± 15.60 3.95 ± 0.48 0.74 bleeding size (cm3) ivh size 0.007 ± 0.017 0.026 ± 0.036 <0.001 total hematoma 0.027 ± 0.037 0.069 ± 0.0589 <0.001 ivh presence yes 19 (35.8) 34 (64.2) <0.001 no 103 (88.8) 13 (11.2) serum glucose (mmol/l) mean ± sd 7.9 ± 2.7 11.1 ± 6.2 <0.001 blood pressure (mmhg) systolic 155.4 ±31.2 168.5 ± 42.1 0.028 diastolic 77.9 ± 15.8 86.1 ± 18.5 0.005 cell blood counts wbc (109 cells/l) 9.2 ± 2.8 10.4 ± 3.9 0.037 platelet (109 cells/l) 235.3 ± 63.8 231.2 ± 98.9 0.754 hemoglobin (mg/dl) 13.3 ± 1.8 12.8 ± 2.0 0.131 data are presented as mean ± standard deviation (sd) or frequency (%). ivh: intraventricular hematoma; wbc: white blood cell. glucose level is significantly associated with mortality in ich patients (19, 20). some other investigations showed that hypoglycemia is not a strong predictor for mortality (13, 21-23). it is also demonstrated that, acute hyperglycemia in patients with stroke, can be reflective of adverse findings in mri and stereoscopy studies (23). in the present study, non-survived patients had significantly higher serum glucose level. in line with the findings of taha nisa, et al. and in disagreement with suspekt score, there was no significant association between the mean age of patients and mortality (24). it is shown that volume of ich can significantly predict 30day mortality (11, 25). in addition, existence and size of ivh, is significantly associated with final outcome (26, 27). it is shown that increased hemorrhage predisposes patients to die within 4 weeks after stroke (28). based on our findings, both ivh and total hematoma size were significantly higher in non-survived patients. regarding the association of serum potassium level and mortality, the finding of this study was in disagreement with the findings of the suspekt score derivation study. the suspekt score is difficult to calculate and based on our findings it seems that we need further comprehensive research before considering the suspekt score as a screening test in our routine practice. the weight of some variables, such as serum potassium and age, in predicting mortality should be reevaluated and some factors such as the location of hemorrhage, cause of hemorrhage, and etc. should be more considered in future studies. performing large-scale and multi-centric studies for assessing the value of suspekt score can be helpful for evaluating the generalizability of findings. 5. limitation small sample size and focusing on the patients of one center were among the limitations of the present study. 6. conclusion based on the findings of the present study, the total accuracy of suspekt score in predicting one-month mortality of ich patients is in good range and it has 82% sensitivity and 92% npv in this regard. 7. appendix 7.1. acknowledgements we would like to thank all the staff of imam hossain hospital who helped us perform this research. this paper is derived from the thesis project of dr. saljughi to earn her specialist degree in shahid beheshti university of medical sciences. 7.2. author contribution the authors met the standard criteria for authorship based on the recommendations of the international committee of medical journal editors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e56 authors orcids hamid kariman: 0000-0001-8082-0356 hamidreza hatamabadi:0000-0002-9085-8806 majid shojaei: 0000-0001-6819-9237 7.3. funding/support none. 7.4. conflict of interest there is no conflict of interest. references 1. qureshi ai, mohammad ym, yahia am, suarez ji, siddiqui am, kirmani jf, et al. a prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage. journal of intensive care medicine. 2005;20(1):34-42. 2. steiner t, al-shahi salman r, beer r, christensen h, cordonnier c, csiba l, et al. e uropean s troke o rganisation (eso) guidelines for the management of spontaneous intracerebral hemorrhage. international journal of stroke. 2014;9(7):840-55. 3. sahni r, weinberger j. management of intracerebral hemorrhage. vascular health and risk 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factor for stroke death in japan: nippon data80. stroke. 2004;35(8):1836-41. 27. wong k. risk factors for early death in acute ischemic stroke and intracerebral hemorrhage: a prospective hospital-based study in asia. stroke. 1999;30(11):232630. 28. brott t, broderick j, kothari r, barsan w, tomsick t, sauerbeck l, et al. early hemorrhage growth in patients with intracerebral hemorrhage. stroke. 1997;28(1):1-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e64 ca s e re p o rt legal considerations of covid-19 patients’ disposition in emergency department; report of 10 cases dorsa najari1, alireza zali1, fares najari1∗, david soroosh2 1. functional neurosurgery research center, shohada tajrish neurosurgical center of excellence, shahid beheshti university of medical sciences, tehran, iran. 2. department of legal medicine, sabzevar university of medical sciences, sabzevar, iran. received: may 2020; accepted: may 2020; published online: 27 june 2020 abstract: covid-19 pandemic is a challenge in the current era. the spread of this viral infection began in wuhan city in china, and iran was also one of the countries struggling with it. considering the nature of this virus and the current pandemic, it is essential that the healthcare system authorities issue a clear and firm law on treating people infected with covid-19 to prevent the consequences affecting the professional life of physicians and healthcare staff. the current study aimed at evaluating the legal consequences of covid-19 cases in emergency department (ed). this case series reported 10 patients that filed complaints against medical staff for problems that occurred on arrival, during the hospital stay or discharge in shohada-ye-tajrish and shahid modarres educational hospitals, tehran, iran. consultation with forensic medicine department was requested for all patients and the final decision for each case was reported under the title legal considerations. keywords: covid-19; severe acute respiratory syndrome coronavirus 2; legal considerations; forensic medicine; legal medicine cite this article as: najari d, zali a, najari f, soroosh d. legal considerations of covid-19 patients’ disposition in emergency department; report of 10 cases. arch acad emerg med. 2020; 8(1): e64. 1. introduction covid-19 is a newly emerging viral disease, whose spread began in wuhan city, china, in december 2019 and rapidly spread worldwide (1-4). iran was one of the affected countries that experienced extensive hospital referrals due to acute respiratory system involvement, along with other symptoms. although patients were not treated with any particular drug or vaccine, the physicians faced moral and legal aspects of the disease. under such circumstances, the responsibility of making decisions about home quarantine, patient discharge, calling healthcare workers back to work after recovery from infection, etc., lied on the shoulders of firstline physicians (5-8) . the extensive patient load of emergency departments (eds), as well as the lack of adequate knowledge of the virus behavior on a global scale, were other problems these physicians faced. during the covid-19 pandemic, most of the ethical principles in medicine such as pa∗corresponding author: fares najari; department of forensic medicine, school of medicine, shahid beheshti university of medical sciences, tehran, iran. tel: +98 (912) 3195140, email: najari.hospital@sbmu.ac.ir tient’s rights, became challenging. the current protocols do not clearly indicate how to deal with a non-cooperative patient; this can become legally and ethically challenging for physicians (9-11). therefore, the current study aimed at evaluating these ethical and legal issues by reporting some cases. the current case series study reports 10 patients who filed complaints against medical staff for problems that occurred on arrival, during the hospital stay or discharge in shohada-ye-tajrish and shahid modarres educational hospitals, tehran, iran, from 20.02.2020 to 19.04.2020. consultation with forensic medicine department was requested for all patients and final decisions for each case was reported. patients with suspected covid-19 infection were excluded, and there were no gender or age limitations in the study. all the data collected from patients remained confidential. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences (research plan tracking code is ir.sbmu.retech.rec.1399.164). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. najari et al. 2 2. case presentation 2.1. case1: the patient was a 51-year-old overweight female with critical conditions complaining of dyspnea, cough, and myalgia, vertigo, taste disorder, and hyposmia. she was admitted to the emergency department (ed) for further examinations. her vital signs were: temperature (t) = 38/5◦.c, blood pressure (bp) = 120/80 mmhg, pulse rate (pr) = 104/min, respiratory rate (rr) = 24/min, o2 saturation (spo2) = 93% in room air, and blood sugar (bs) = 112 mg/dl. after performing chest ct scan and other laboratory tests, her infection with covid-19 was confirmed. despite the physician’s advice, she refused to stay in the hospital due to the challenge of the family. legal considerations in the examination of the patient from legal aspects, she was alert and oriented. she was married and had a 14-year-old child; her level of education was a high school diploma. she was well oriented, could answer the questions consciously, and was capable of taking care of herself. she had no problems with home-based self-quarantine, and her physician believed that she would be okay at home, and there was no need for the hospital stay since she was not in a critical condition. therefore, despite her infection with a lethal virus, there was no action to prohibit her from discharge; hence, the patient was discharged with prescription and advice about alarming signs and revisiting after two weeks of home quarantine. 2.2. case2: the patient was a 63-year-old male with obesity, cold symptoms, and loss of taste and smell senses, which had started five days before the visit. he was admitted to the ed, and his vital signs were: t = 39.5◦c, bp = 105/70 mmhg, pr = 104/min, rr = 24/min, spo2 = 90% in room air, and bs = 122 mg/dl. he also had heroin addiction. he was diagnosed with covid-19 infection based on pcr results. he had withdrawal signs and respiratory distress due to infection in the lower respiratory tract. legal considerations the patient had been a heroin addict for about 15 years. he had a high school diploma and was not willing to stay in hospital due to addiction; but his discharge could be a hazard to society, due to infection with covid-19. therefore, due to his unstable conditions and in order to prevent worsening of the covid-19 outbreak, his admission to intensive care unit (icu) was recommended. he received iv medications for addiction withdrawal in addition to routine covid-19 treatments. his discharge was prohibited, and since he could not make his own medical decisions, the healthcare system informed the hospital authorities. 2.3. case3: a 57-year-old male patient with obesity and type 2 diabetes complaining of myalgia and shortness of breath, taste disorder, and vertigo, referred to the hospital. his vital signs were: t = 39◦c, bp = 100/80 mmhg, pr = 114/min, rr = 27/min, spo2 = 88% in room air, and bs = 222 mg/dl. he was admitted to the general ward but then transferred to the icu due to infection with covid-19. his family insisted on transferring him to a private hospital. legal considerations the patient was not conscious and could not make his own medical decisions. due to patient overload in the ed, his eldest son decided to transfer him to a private hospital. finally, the supervisor of the hospital accepted the patient’s transfer, while he should make sure that all the hygienic protocols were observed and the patient was safely admitted to that hospital. if a patient cannot make his/her medical decisions, the family members attending the center can make the decision. written consent was obtained from them immediately. 2.4. case4: a 66-year-old male physician with obesity, who was constantly in contact with infected patients and had a history of recto-sigmoid tumor and chemotherapy was diagnosed with covid-19 infection. his vital signs were: t = 38◦c, bp = 130/80 mmhg, pr = 114/min, rr = 27/min, spo2 = 96%, and bs = 99 mg/dl. he insisted on staying at home for treatment completion. legal considerations considering the patient’s occupation and his familiarity with medical procedures and protocols of quarantine, he was discharged for a home-based self-quarantine for 14 days. he was warned to get back to the hospital if any of the symptoms worsened. 2.5. case5: the patient was a 38-year-old female in her 36th week of gestation admitted to the ed with complaints of typical covid19 symptoms (fever, myalgia, shortness of breath) as well as olfactory and taste disorders. her vital signs were: t = 38.5 ◦c, bp = 100/70 mmhg, pr = 100/min, rr = 27/min, spo2 = 90%, bs = 99 mg/dl, and had no history of abortions or any other maternity problems. after routine examinations and laboratory tests, she was diagnosed with covid-19 infection, but her husband wanted to take her home. legal considerations examinations revealed that she was well-oriented and capable of making her own medical decisions. according to the current laws, her husband could not discharge her despite her will. the only rights that husband and wife have toward each other are the ones indicated in the marriage contract. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e64 table 1: characteristics of reported cases cases gender age condition pcr igm igg chest ct scan c1 female 51 ill pos+ pos+ negnot significant c2 male 63 not good pos+ pos+ pos+ haziness in the right lobe c3 male 57 ill pos+ pos+ pos+ haziness in the right and left lobes c4 male 66 fair pos+ pos+ negnormal c5 female 38 ill pos+ negnegnormal c6 female 40 bad negpos+ negtiff in the right lobe c7 male 47 bad pos+ pos+ pos+ haziness in the right and left lobes c8 male 39 ill pos+ pos+ negnot done c9 female 61 bad negpos+ pos+ haziness in the right lobe c10 female 48 good negnegpos+ normal pcr: polymerase chain reaction; ct: computed tomography. in addition, the fetus’s health was engaged with that of the mother; therefore, the patient could not be discharged. 2.6. case6: a 40-year-old nurse who had previous contact with patients infected with covid-19 and was obese but had no history of any particular disease was admitted to ed; her vital signs were: t = 39.5◦c, bp = 125/70 mmhg, pr = 85/min, rr = 20/min, spo2 = 96%, and bs = 88mg/dl. she had a high fever and shortness of breath, hyposmia, taste disorder and her chest ct scan showed a mild bilateral pleural effusion with haziness in the lower respiratory tract. she did not want to complete her treatment in the hospital since she had a young child. legal considerations although she was a member of the healthcare staff, due to the worsening of her health status, she could not be discharged despite her own will. she was not capable of taking care of herself, her child, and other family members, and did not have adequate facilities for home-quarantine. 2.7. case7: the patient was a 47-year-old male with obesity admitted to icu due to infection with covid-19. his vital signs on admission were: t = 39.5◦c, bp = 95/70 mmhg, pr = 144/min, rr = 30/min, spo2 = 80%, and bs = 86 mg/dl. unfortunately, he expired after five days. his family wished to get his corpse and hold a funeral. legal considerations this patient passed away due to infection with the new coronavirus; therefore, the cause of death had to be written clearly and legibly in the death certificate, and the corpse had to be transferred to the cemetery under restricted terms by special ambulance. therefore, the corpse was not handed to the family. 2.8. case8: the patient was a 39-year-old male; he was overweight and had severe cold-like symptoms similar to those of covid-19 as well as taste disorder and had drunk handmade alcohol to ease his problem. unfortunately, he arrived at the hospital too late due to loss of consciousness, snowstorm in both eyes, and respiratory distress. his vital signs were: t = 36.5◦c, bp = 95/70 mmhg, pr = 67/min, rr = 34/min, spo2 =78%, and bs = 182 mg/dl. medical evaluations revealed severe metabolic acidosis with serum methanol and ethanol levels of 60 and 140 mg/dl, respectively. he was also diagnosed with covid-19 infection based on pcr results. despite all the interventions, including hemodialysis (due to methanol intoxication), twice, he expired after 36 hours. legal considerations considering the prohibition of alcohol consumption in iran and the fact that the patient had consumed alcohol to treat his disease due to existing rumors, it was the responsibility of the attorney general of tehran to confront those spreading these rumors. his death certificate could be issued without an autopsy, since the cause of his death was methanol intoxication. 2.9. case9: the patient was a 61-year-old female with obesity and no history of drug abuse or disease. she had flu-like symptoms, olfactory disorder and considering the pandemic of covid-19, her friends advised her to inhale opium to ease her conditions. she arrived at the hospital too late following respiratory distress. her vital signs were: t = 37◦c, bp = 100/80, pr = 65/min, rr = 34/min, spo2 = 87%, and bs = 77 mg/dl; her pcr result for covid-19 was positive. in addition, her morphine test result was positive, but she claimed that she had no idea about using drugs. legal considerations the patient did not want her parents to be informed about drug abuse. therefore, since she was an adult and no conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. najari et al. 4 sent was required, her drug abuse could not be elucidated, and she was treated for covid-19 infection and the adverse effects of the drug. 2.10. case10: the patient was a 48-year-old overweight female, who had a history of asthma for 15 years and took corticosteroids. she had symptoms of covid-19 infection including fever and shortness of breath, as well as hyposmia but normal vital signs. her chest x-ray showed haziness in the lower part of the right lung lobe, but the chest ct scan image showed healthy lungs. her covid-19 igm test and pcr results were negative, but the covid-19 igg test was positive. the firstyear general practice resident refused to discharge her due to suspicion of infection. legal considerations after more evaluations from a legal point of view and studying her blood gas analysis, it seemed that her asthma was poorly controlled during the past months. she was discharged after consultation with an infectious disease specialist since her infection with covid-19 was improbable. characteristics of reported cases are summarized in table 1. 3. discussion according to the legal and canonical sources in iran, there are six groups of interdicted people, who cannot be in charge of actions: 1) people with fatal diseases, 2) children, 3) mentally-ill people, 4) insane people, 5) slaves, and 6) real bankrupts (12-14). people infected with covid-19 are assigned to the first group, which includes all the patients admitted to ed, icu, critical care unit (ccu), etc., as such patients are infected with a fatal disease and are also a major risk for the health of society. consequently, since they are not in the condition to think for themselves, the healthcare system should make medical decisions for them (15-18). as mentioned in the article by cristina cattaneo, covid-19 has affected the practice of forensic medicine. in the previous years, the focus had been on preparing protocols for recovery and identification of victims or collecting evidence and recreating the victims’ manner of death in disasters such as explosions, tsunamis, and mass disasters, or homicide, child abuse, or manslaughter, which are very different from a virus pandemic in nature. the pandemic has not only forced a reduction in medicolegal autopsies it has also increased the number of living victims in need of medicolegal services. while in some cases the victims cannot be assisted due to lockdown or restrictions (19). we are faced with global economic and social issues in addition to our healthcare system challenges. mandatory quarantine was an approach used in many countries, but it has its own drawbacks too. for example, governments must ensure that people’s basic needs are met and that they have access to healthcare, medication, food, and sanitation. this is critical to ensure that they will comply with orders (20). in the article by terry skolnik (21) it is stated that this global pandemic has provided an opportunity for judges, policy makers and justice system actors to make lasting positive changes to the system, similar to those observed during the pandemic. we could not find any similar studies as in most studies the issue has been addressed only from a diagnostic and therapeutic point of view and there is no mention of legal issues at all. in the event of any legal issues for patients, we suggest consulting with forensic experts. 4. conclusion it is necessary for the healthcare system to update itself based on the latest guidelines and interventions for covid-19 and facilitate legal assistance in order to prevent future prosecutions. 5. declarations 5.1. acknowledgements all staff members who helped perform the study are acknowledged. 5.2. authors contribution all authors contributed in designing, running, and writing all parts of the research. authors orcids fares najari: 0000-0003-0645-0566 5.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 5.4. funding/support no funds have been received for doing this project. references 1. liu j, qin x, qiu s, yuan y, zong y, tuo z, et al. the lancet respiratory medicineclinical characteristics and treatment of patients infected with covid-19 in shishou,china. 2020. 20-00141. 2. lei l, jian-ya g. clinical characteristics of 51 patients discharged 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& public health-special issue. 2018:25-34. 11. najari f, baradaran i, d. n. methanol poisoning and its treatment. international journal of medical toxicology and forensic medicine. . 2020;10(.126639). 12. najari f, mostafazadeh b, bahrami m, najari d. causes and frequency of physical trauma in pregnancy. tehran university medical journal. 2019;77(3):166-71. 13. mostafazadeh b, najari f, emamhadi m, ghaedi g. assessing informed consent in medical malpractice cases associated with different surgical fields referring to tehran’s commission of forensic medicine, 2017. novelty in biomedicine 2020;8(1). 14. najari f, mostafazadeh b, soleimani natanzi l. complications of laparoscopic and laparotomy surgeries in the department of tehran legal medical committee in 20112016. international journal of medical toxicology and forensic medicine. 2019;9(2):83-90. 15. gao j, tian z, yang x. breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid-19 associated pneumonia in clinical studies. bioscience trends. 2020;14(1):72-3. 16. dadpour b, faghani r, vahabzadeh m, davoudi y, najari f. brain structure changes associated with methamphetamine abuse in brain magnetic resonance imaging. nternational journal of medical toxicology and forensic medicine. 2019;3(9):103-8. 17. dadpour b, hatami z, liaghat a, eshraghi a, najari f, najari d. assessment of qt dispersion in electrocardiogram of patients with acute poisoning of methadone. tehran university medical journal. 2019;77(7):453-7. 18. shabani ak, najari f, jannani f, khadijeh e, montazer khorasan mr, masoumi h, et al. type a botulism outbreak in members of a family following consumption of homemade whey: brief report. tehran universitymedical journal. 2020;77(11):720-33. 19. cattaneo c. forensic medicine in the time of covid 19: an editorial from milano, italy. forensic sci int. 2020;312:110308-. 20. parmet we, sinha ms. covid-19 – the law and limits of quarantine. new england journal of medicine. 2020;382(15):e28. 21. skolnik t. criminal law during (and after) covid-19. manitoba law journal, forthcoming available at ssrn: https://ssrncom/abstract=35990212020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references emergency. 2018; 6 (1): e13 le t t e r to ed i to r dissimilarity in the frequency of venous thromboembolism risk factors among studies, a commentary meghdad sedaghat1∗, mahsa soltani1, mehrdad solooki2 1. department of internal medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of pulmonary and critical care medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: january 2018; accepted: february 2018; published online: 18 febryary 2018 cite this article as: dissimilarity in the frequency of venous thromboembolism risk factors among studies, a commentary. emergency. 2018; 6(1): e13. dear editor; venous thromboembolism (vte) is the 3rd most prevalent vascular disease behind myocardial infarction and cerebrovascular ischemic attack (1). this disorder has received attention from health policy makers because of its major complications including recurrent vte, post thrombotic syndrome, sudden cardiac death and high mortality rate (2). in the united states, vte was reported in approximately 201000 cases annually, 25% of which expired within 7 days after diagnosis and 22% of mortalities did not have a definitive diagnosis. despite the progression in diagnosis and treatment of vte since 1979, its incidence did not decrease dramatically. this gap declares that vte risk factors, especially transient ones, have not been detected completely (3). obesity, history of vte, family history of vte, recent surgery, malignancy, myeloproliferative disorders, trauma, pregnancy, post-menopausal hormone therapy, hereditary syndromes like anti phospholipid syndrome (aps), chronic kidney disease (ckd), chronic obstructive pulmonary disease (copd), blood transfusion and older age are determined as major risk factors. these factors can be categorized into two major subgroups as intrinsic and predisposing. recent investigations focused on predisposing ones, which can be justified (2, 4). designing a cross sectional study in imam hossein hospital, tehran, iran, from 2016 to 2017, we found that inactivity due to disability (30.9%), smoking (29.3%), and active malignancy (18.1%), were the most prevalent transient risks factor of vte in our sample, respectively. similar to our results, kesieme et al. (5) and cushman et al. (2) declared that vte is more ∗corresponding author: meghdad sedaghat; department of internal medicine, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. email: sedaghat6161@gmail.com phone: 00989128121361 diagnosed in the elderly. park ms et al. (3) introduced recent surgery, trauma (73%), and disability to walk (62%) as major independent risk factors of vte. fuji t et al. (6) introduced malignancy, recent infectious disease, and obesity as the factors predisposing patients who were admitted for orthopedic surgery to vte. as can be seen, despite the risk factors of vte being the same in various studies, their frequency varied between the studies. population and cultural characteristics and various habits may have an effect in this regard. therefore, it is suggested to perform a multi-center, comprehensive study considering all the racial and ethnic in order to have a correct pattern of the frequency of predisposing factors of this disease in the iranian population for health and prevention programs. 1. appendix 1.1. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. 1.2. funding/support none. 1.3. conflict of interest the authors declare that there is no conflict. references 1. navarro-carpentieri d, castillo-hernandez mdc, majlufcruz k, espejo-godinez g, carmona-olvera p, morenohernandez m, et al. impact of classical risk factors for arterial or venous thrombosis in patients with antiphosthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. sedaghat et al. 2 pholipid syndrome.clin appl thromb hemost. 2017 jan 1:1076029617727859. 2. cushman m. epidemiology and risk factors for venous thrombosis. semin hematol. 2007 apr; 44(2): 62-69. 3. park ms, perkins se, spears gm, ashrani aa, leibson cl, boos cm, harmsen ws,jenkins dh, bailey kr, ballman kv, heit ja. risk factors for venous thromboembolism after acute trauma: a population-based case-cohort study. thromb res. 2016 aug;144:40-5. 4. giordano nj, jansson ps, young mn, hagan ka, kabrhel c. epidemiology,pathophysiology, stratification, and natural history of pulmonary embolism. tech vasc interv radiol. 2017 sep;20(3):135-140. 5. kesieme e, kesieme c, jebbin n, irekpita e, dongo a. deep vein thrombosis: a clinical review. journal of blood medicine 2011:2 59–69. 6. fuji t, akagi m, abe y, oda e, matsubayashi d, ota k, et al. incidence of venous thromboembolism and bleeding events in patients with lower extremity orthopedic surgery: a retrospective analysis of a japanese healthcare database. j orthop surg res. 2017 apr 4;12(1):55. 7. wang c, zhai z, yang y, wu q, cheng z, liang l, et al.; china venous thromboembolism (vte) study group. efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter,controlled trial. chest. 2010 feb;137(2):254-62. 8. yilmazel ucar e, araz o, kerget b, yilmaz n, akgun m, saglam l. comparison of long-term outcomes of 50 and 100 mg rt-pa in the management of acute pulmonary thromboembolism. clin respir j. 2017 oct 17. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2019; 7 (1); e42 ph oto qu i z a 92-year-old man with abdominal pain following intractable vomiting; a photo quiz chin-chu wu1, aming chor-ming lin2,3∗ 1. department of diagnostic radiology, shin kong wu ho-su memorial hospital, taipei, taiwan. 2. emergency department, shin kong wu ho-su memorial hospital, taipei, taiwan. 3. school of medicine, fu-jen catholic university, new taipei city, taiwan. received: june 2019; accepted: july 2019; published online: 6 august 2019 cite this article as: a 92-year-old man with abdominal pain following intractable vomiting; a photo quiz. arch acad emerg med. 2019; 7(1): e42. figure 1: posterior-anterior chest x-ray (left) and coronal view of abdominal computed tomography scan (right) of patient. 1. case presentation a 92-year-old man with hypertension, chronic obstructive pulmonary disease (copd), peptic ulcer disease and dementia presented to the emergency department with a 2-day history of abdominal pain in the left upper quadrant, distention, dry cough and intractable vomiting. on physical examination, the patient had epigastric tenderness and bowel sounds were reduced. the patient’s vital signs included blood pressure of 168/84 mmhg, heart rate of 99 beats/minutes, respiratory rate of 24 beats/minutes, and oxygen saturation of 95% in room air. his temperature was 37.9◦c. the rest of physical examination findings were unremarkable. complete blood cell count showed the following results: leukocyte count 10100/mm3 with 85% segmented neutrophils, hemoglobin 12 g/dl, platelet 350000/microliter, and international normalized ratio (inr) of 0.97. other laboratory findings included: glucose 167 mg/dl, blood urea nitrogen (bun) 28 mg/dl, serum creatinine 2.0 mg/dl, sodium 135 meq/l, potassium 3.3 meq/l, serum glutamic oxaloacetic transaminase (sgot) 15 u/l, total bilirubin 0.5 mg/dl, and lipase 25 u/l. the patient underwent chest x-ray and abdominal computed tomography (ct) scan without contrast material, the results of which are shown in figure 1. what is your diagnosis? 2. diagnosis chest x-ray showed left lower lung interstitial opacities and air bubble below the left hemi diaphragm (figure 1 (left), arrows). abdominal ct scan revealed intramural gas within a this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem ch. wu and a. lin 2 dilated stomach (figure 1 (right), arrow). a diagnosis of gastric emphysema was made. 3. case fate the patient was not toxically ill and recovered with conservative management of nasogastric decompression, intravenous fluids, total parenteral nutrition and intravenous antibiotics. the patient was discharged from the hospital 7 days after presentation. 4. discussion gastric emphysema is characterized by the presence of air within the wall of the stomach. gas within the stomach wall is an alarming finding on imaging. early recognition is essential. the gas may be caused by gastric pneumatosis, also known as gastric emphysema or emphysematous gastritis (1). it is important to differentiate the causes of gastric pneumatosis. gastric emphysema is usually asymptomatic and relatively benign, and resolves spontaneously with conservative treatment with bowel rest, parenteral nutrition and wide spectrum antibiotics. gastric emphysema is a rare condition in which gas accumulates within the wall of the stomach. gastric distension and frequent vomiting precede the formation of the intramural air. pulmonary disease, instrumentation of the stomach, and obstructing lesions of the antrum and pylorus are also common contributing factors. emphysematous gastritis is a lethal condition with high mortality (2, 3). surgery is indicated in emphysematous gastritis because of gastric infarction, perforation or failed medical management. emphysematous gastritis is characterized by the presence of gas in the wall of the stomach and is a severe form of phlegmonous gastritis, which develops due to invasion by gas-forming microorganisms. air within the gastric wall along with portal venous air, sepsis and evidence of infection support the diagnosis of emphysematous gastritis (1, 2). the radiographic finding of gastric emphysema with hepatic portal venous gas is classically an ominous sign, associated with a high mortality rate. diabetes mellitus, immunosuppression, alcohol abuse, ulcerative colitis and use of non-steroidal anti-inflammatory drugs (nsaid) have all been reported as predisposing factors (4, 5). the most commonly involved microorganisms are streptococci, escherichia coli, pseudomonas aeruginosa, clostridium perforins and staphylococcus aureus. abdominal ct scan is the diagnostic tool of choice to detect gastric pneumatosis and helps in differentiating it with gastric emphysema or emphysematous gastritis. 5. conclusion: the presence of gas within the stomach wall may be associated with a wide range of conditions, ranging from benign to fatal. early recognition by abdominal ct scan and prompt treatment are essential to improve survival. 6. appendix 6.1. acknowledgements we acknowledge all the staff of diagnostic radiology and emergency departments of shin kong wu ho-su memorial hospital, taipei, taiwan. 6.2. conflict of interest none. 6.3. funding and support none. 6.4. authors’ contributions all authors passed four criteria for authorship contribution based on recommendations of the internal committee of medical journal editors. authors orcids chin-chu wu: 0000-0003-2658-5775 references 1. matsushima k, won ej, tangel mr, enomoto lm, avella dm, soybel di. emphysematous gastritis and gastric emphysema: similar radiographic findings, distinct clinical entities. world journal of surgery. 2015;39(4):1008-17. 2. yalamanchili m, cady w. emphysematous gastritis in a hemodialysis patient.(case report). southern medical journal. 2003;96(1):84-9. 3. paul m, john s, menon mc, golewale nh, weiss sl, murthy uk. successful medical management of emphysematous gastritis with concomitant portal venous air: a case report. journal of medical case reports. 2010;4(1):140. 4. jehangir a, rettew a, shaikh b, bennett k, qureshi a, jehangir q. a case report of emphysematous gastritis in a diabetic patient: favorable outcome with conservative measures. journal of community hospital internal medicine perspectives. 2015;5(4):28010. 5. inayat f, zafar f, zaman ma, hussain q. gastric emphysema secondary to severe vomiting: a comparative review of 14 cases. bmj case reports. 2018;2018:bcr-2018-226594. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem case presentation diagnosis case fate discussion conclusion: appendix references archives of academic emergency medicine. 2020; 8(1): e22 ca s e re p o rt anaphylaxis as a rare side effect of ketorolac; a case report hesam yousefi1, ali sahebi2, mahtab farahani3, mohamad golitaleb4∗ 1. department of pharmaceutical care, sajad hospital, kermanshah, iran. 2. clinical research development unit, shahid mostafa khomeini hospital, ilam university of medical sciences, ilam, iran. 3. student research committee, department of nursing, school of nursing, arak university of medical sciences, arak, iran. 4. department of nursing, school of nursing, arak university of medical sciences, arak, iran. received: january 2020; accepted: february 2020; published online: 17 march 2020 abstract: anaphylaxis is a life-threatening systemic allergic hypersensitivity reaction that may potentially be triggered after the administration of any drug. our case was a 51-year-old man with the history of mild pain in his flanks since the night before he was admitted to our hospital. the patient was diagnosed with urolithiasis and admitted to the emergency department. he developed anaphylaxis after intravenous injection of 30 mg ketorolac. allergic reactions to non-steroidal anti-inflammatory drugs (nsaids) such as ketorolac are rare; nonetheless, they can be life-threatening and should be carefully monitored. keywords: anaphylaxis; drug hypersensitivity syndrome; adverse drug reaction; nsaids; ketorolac cite this article as: yousefi h, sahebi a, farahani m, golitaleb m. anaphylaxis as a rare side effect of ketorolac; a case report. arch acad emerg med. 2020; 8(1): e22. 1. introduction non-steroidal anti-inflammatory drugs (nsaids) constitute a broad spectrum of cyclooxygenase (cox) inhibitors suppressing prostaglandin synthesis. nsaids are used for treating various conditions such as pain, rheumatoid arthritis, osteoarthritis, and musculoskeletal disorders (1). ketorolac is an nsaid, which is used to alleviate renal colic due to its anti-contractile effects on the urethra. considering the pain pathogenesis in renal colic, ketorolac is one of the best painrelieving drugs in these patients (2). in intravenous form, this drug reaches its serum peak level within 1 to 3 minutes. ketorolac is metabolized in the liver and excreted through the kidneys (2). although ketorolac has an excellent safety profile, allergic reactions and anaphylaxis may occur following its administration. even though these reactions, either acute or delayed, are uncommon and rare, they can be fatal (3). a number of studies have reported anaphylactic reactions after ketorolac administration. however, the incidence of these reactions is not predictable (4-6). here, we present a case of ∗corresponding author: mohamad golitaleb; department of nursing, school of nursing, arak university of medical sciences, basij square, arak, iran. email: m.golitaleb@arakmu.ac.ir, phone: +988634173504, fax: +988634173524 anaphylaxis in a male patient admitted to the emergency department of vali-e-asr hospital, arak, iran, following the injection of 30 mg ketorolac. 2. case presentation our patient was a 51-year-old man who had mild pain in his flanks since the night before presenting to the emergency department of vali-e-asr hospital of arak, iran, because the pain had worsened and disseminated to abdominal area. the pain was initially localized in the patient’s right flank propagating to the thighs and testicles afterwards. the pain repeatedly decreased and restarted over a short period of time. the patient was restless and anxious while constantly changing his posture. the patient also suffered from nausea, vomiting, hematuria, polyuria, and dysuria. the patient had a history of surgery due to urolithiasis in his left kidney three years ago. the vital signs upon admission were as follows: heart rate (hr) = 103 beat/min, respiratory rate (rr) = 23 beat/min, o2 saturation = 96% (in room air), and blood pressure (bp) = 153/97 mmhg. after taking medical history from the patient and his companions, the patient was diagnosed with urolithiasis. following insertion of a peripheral iv-line, 30 mg of diluted intravenous ketorolac (produced by: alborz darou pharmaceuticals company, iran) was slowly inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. yousefi et al. 2 jected. 2 minutes after the initiation of drug injection, the patient developed itching, redness of upper extremities, urticaria, angioedema, hypotension, cyanosis, and dyspnea. the patient’s vital signs were immediately checked and the following values were retrieved: hr = 148 beat/min, rr = 7 beat/min, bp = 75/50 mmhg, and o2 saturation = 72% in room air. the anaphylactic shock was immediately managed by infusion of 30 ml/kg normal saline, 0.5 mg intramuscular epinephrine (1:1000), 200 mg of intravascular hydrocortisone, and 4 mg intravenous chlorpheniramine. oxygen was further administrated through nasal cannula at the rate of 8 liters per minute. fortunately, the patient’s general condition gradually improved and completely recovered after 1 hour. after the reaction, 1 gram of intravenous paracetamol (acetaminophen) diluted in 100 cc in normal saline was used to control the pain. the patient was discharged after 8 hours. 3. discussion anaphylaxis is a life-threatening systemic allergic reaction affecting the cardiovascular and respiratory systems. mast cells and basophils are major contributors to anaphylaxis. drugs are among the most common causes of anaphylaxis. delay in treatment of anaphylaxis can lead to hypoxia, ischemia, encephalopathy, and finally death (7, 8). the side effects of ketorolac include reflux (at prolonged usage), nausea, indigestion, and bronchospasm (in susceptible individuals) (2, 3). acute and delayed systemic allergic reactions can occur following oral or intravenous administration of this drug (9). chung et al. reported a 41-year-old male who had been admitted to the emergency department with the diagnosis of acute gastric ulcer perforation. the patient underwent surgery for correcting perforation and was infused with ketorolac loading dose (i.e. 16.2 mg per hour) after surgery to alleviate pain. the patient developed anaphylactic reaction after 1 hour and forty minutes of the drug administration (6). oliva et al. reported a 53-year old female with severe depression who had committed suicide by consuming 3 vials of 30 mg ketorolac. laboratory investigations (i.e. hematologic tests, as well as histological and toxicological findings) and autopsy results confirmed the cause of death as anaphylactic reaction following ketorolac infusion (4). scala et al. reported a 60-year-old woman developing respiratory problems, decreased consciousness, hypotension, and laryngeal edema after oral consumption of 10 mg ketorolac tablet. the patient and her family had no history of allergic diseases, sinusitis, nasal polyps, or drug hypersensitivity. also, the patient declared that she had not consumed anything before taking ketorolac (5). 4. conclusion allergic reactions following the administration of nsaids such as ketorolac are rare. however, such reactions can be life-threatening if they occur. physicians and nurses working in different hospital wards, especially the emergency department, should be aware of this side effect of ketorolac. they must carefully monitor patients’ condition during and after the injection of this drug to identify this fatal complication in a timely manner. 5. declaration 5.1. ethical consideration the scientific value of presenting this case was fully described to the patient and an informed consent was obtained from him before submission. all procedures performed in the present study were in accordance with the standards of the ethical committee of arak university of medical sciences and the 1964 helsinki declaration. 5.2. authors contribution all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. authors orcids mohamad golitaleb: 0000-0002-9216-9262 hesam yousefi: 0000-0003-3837-8490 ali sahebi: 0000-0003-4662-8998 mahtab farahani: 0000-0001-9841-3716 5.3. conflict of interest authors have no conflict of interest. 5.4. funding none. references 1. cabassi a, tedeschi s, perlini s, verzicco i, volpi r, gonzi g, et al. non-steroidal anti-inflammatory drug effects on renal and cardiovascular function: from physiology to clinical practice. european journal of preventive cardiology. 2019:2047487319848105. 2. mallinson te. a review of ketorolac as a prehospital analgesic. journal of paramedic practice. 2017;9(12):522-6. 3. cerreta aj, masterson ca, lewbart ga, dise dr, papich mg. pharmacokinetics of ketorolac in wild eastern box turtles (terrapene carolina carolina) after single intramuscular administration. journal of veterinary pharmacology and therapeutics. 2019;42(2):154-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e22 4. oliva a, de fg, arena v, fucci n, pascali vl, navarra p. death due to anaphylactic shock secondary to intravenous self-injection of toradol: a case report and review of the literature. clinical toxicology (philadelphia, pa). 2007;45(6):709-13. 5. scala e, giani m, pirrotta l, guerra ec, locanto m, de pita o, et al. selective severe anaphylactic reaction due to ketorolac tromethamine without nonsteroidal antiinflammatory drug intolerance. journal of allergy and clinical immunology. 2001;107(3):557. 6. chung hs, kim es, you yj, park cs. anaphylactoid reaction after injection of ketorolac in a loading dose for patient-controlled analgesia-a case report. korean journal of anesthesiology. 2010;58(6):565. 7. yousefi h, moayedi s, harorani m, sahebi a, golitaleb m. anaphylaxis as a side effect of pantoprazole. shiraz emedical journal. (in press). 8. faridaalaee g, heris ja. anaphylaxis as a rare side effect of pantoprazole; a case report. emergency. 2018;6(1). 9. castillo-zamora c, castillo-peralta la, nava-ocampo aa. report of an anaphylactoid and an anaphylactic reaction to ketorolac in two pediatric surgical patients. therapeutic drug monitoring. 2006;28(3):458-62. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declaration references emergency. 2018; 6 (1): e33 le t t e r to ed i to r medical errors in emergency department; a letter to editor payman asadi1∗, ehsan modirian2, nazanin dadashpour1 1. road trauma research center, guilan university of medical sciences, rasht, iran. 2. emergency department, qazvin university of medical sciences, qazvin, iran. received: april 2018; accepted: may 2018; published online: 21 may 2018 cite this article as: asadi p, modirian e, dadashpour n. medical errors in emergency department; a letter to editor. emergency. 2018; 6(1): e33. dear editor: medical error is the third leading cause of death in the united states of america and almost 100000 patients lose their life due to medical errors every year (1). studies show that the number of medical errors is increasing annually. various factors such as weak communication between medical staff and patients, the activity of the press and other mass media, insurance companies, lawyers and legal advisers, reposition of the doctors, economic problems of the health care team, and etc. have an important role in this increasing trend (2-5). medical errors are generally considered from two perspectives, which include individual approach (traditional) and systemic approach (holistic). in individual approach the initial encounter with an error is finding the guilty person and blaming him/her. in this approach, each individual is responsible for their actions, individually. this approach has a long background in the world of medicine and aims to improve performance with actions like compulsory education, warning, legislation, and punishment. the problem of this approach is that the system is ignored, so it does not reduce medical errors, because the error is influenced by several factors; therefore, blame or even abandoning those who are guilty does not change anything. the systemic approach is an unavoidable phenomenon that can be used to enhance the performance of the system. actually systemic approach is to change the system, so that the probability of error is reduced. when an undesirable event occurs is not important to find out who has made a mistake, but we must examine what has caused the failure of defense mechanisms against errors. system sets of elements (human ∗corresponding author: payman asadi; road trauma research center, poursina hospital, rasht, guilan province, iran. tel: +989111351340; fax: +983117923445; email: payman.asadi@yahoo.com and inhuman) are independent and interact with each other to achieve a common objective. man acts as a part of the system and the last of the cycle and the final performer of the system. for this reason, root causes of medical errors should be managed. overcrowding, shortage of personnel and equipment, and admission of patients with life-threatening diseases has made the emergency departments prone to higher incidence of medical errors. poursina hospital is an educational hospital in rasht, guilan province, north iran, with about 30000 to 35000 admissions per year. performing a cross sectional study, we analyzed the registered cases of medical errors in the hospital during one year. 396 (1.24%) cases of medical errors were reported and emergency department with 134 (33.7%) cases had the highest incidence of medical errors among hospital wards. diagnostic errors with 173 (43.5%) cases and medication errors with 100 (25.1%) were among the most common reported errors. most of the people were not informed regarding their error and there was the possibility that they repeat the same errors. it seems that experienced personnel should be used to reduce the occurrence of medical errors in the crowded wards, which have to support patients with life-threatening diseases. people should be aware that the error registry system has been launched to identify and resolve system errors and it doesn’t aim to identify the offender. 1. appendix 1.1. acknowledgements none. 1.2. author’s contribution all the authors of this article met the criteria of authorship based on the recommendations of the international committhis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. asadi et al. 2 tee of medical journal editors. 1.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 1.4. funding and support none. references 1. donaldson ms, corrigan jm, kohn lt. to err is human: building a safer health system: national academies press; 2000. 2. schenkel s. promoting patient safety and preventing medical error in emergency departments. academic emergency medicine. 2000;7(11):1204-22. 3. sandars j, esmail a. the frequency and nature of medical error in primary care: understanding the diversity across studies. family practice. 2003;20(3):231-6. 4. schwappach dl, koeck cm. what makes an error unacceptable? a factorial survey on the disclosure of medical errors. international journal for quality in health care. 2004;16(4):317-26. 5. tamuz m, thomas e, franchois k. defining and classifying medical error: lessons for patient safety reporting systems. bmj quality & safety. 2004;13(1):13-20. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2019; 7 (1): e61 br i e f re p o rt developing a checklist for cardiopulmonary resuscitation (cpr) quality control in emergency department; a qualitative study mohammad afzalimoghaddam1,5, ehsan karimialavijeh3,5∗, gholamreza zakipour1, hadi mirfazaelian1,5, amir nejati5, pooya payandemehr1,5 1. emergency department, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. 2. emergency department, emergency medicine research center, tehran university of medical sciences, tehran, iran. 3. emergency department, shariati hospital, tehran university of medical sciences, tehran, iran. 4. emergency department, sina hospital, tehran university of medical sciences, tehran, iran. 5. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran received: august 2019; accepted: september 2019; published online: 2 november 2019 abstract: introduction: monitoring the quality of cardiopulmonary resuscitation (cpr) could help in achieving favorable outcomes, decreasing mortality, and preventing post-cpr neurologic sequels. this study aimed to generate a user-friendly checklist for cpr quality control in emergency department (ed). methods: a qualitative study was performed between january and december 2018. in the first step, two emergency medicine specialists searched currently available databases and extracted the factors related to cpr quality. afterward, two sessions of focus group discussions were held. the participants included four emergency medicine specialists, two ed managers, one anesthesiologist, and one cardiologist. subsequently, 20 medical specialists, consisting of 10 emergency medicine specialists, six anesthesiologists, and four cardiologists, were invited to a delphi panel in order to rate the extracted items from the prior group discussions. results: during the two rounds of focus group discussions, 38 items related to the quality of cpr were identified. a delphi panel evaluated the items; 31 items with at least 75% agreement were selected. these 31 items were included in the final checklist and after a pilot study and adjustment of its content they were sorted in 10 categories as follows: 1. chest compression, 2. airway, 3. bag-mask ventilation, 4. cardiac monitoring, 5. defibrillation, 6. intravenous (iv ) drug delivery, 7. medications, 8. advanced airway, 9. cpr sequence, and 10. reversible causes. conclusion: our study provides a checklist for monitoring the quality of cpr in ed, but it is still necessary to include other factors related to the ed environment on this checklist. keywords: cardiopulmonary resuscitation; heart arrest; quality control; emergency medicine cite this article as: afzalimoghaddam m, afzalimoghaddam e, zakipour gh, mirfazaelian h, nejati a, payandemehr p. pan vs. developing a checklist for cardiopulmonary resuscitation (cpr) quality control in emergency department; a qualitative study. arch acad emerg med. 2019; 7(1): e61. 1. introduction monitoring the quality of cardiopulmonary resuscitation (cpr) in the emergency department (ed) is an essential requirement for achieving favorable outcomes, decreasing mortality, and preventing post-cpr neurologic sequels (1). ∗corresponding author: ehsan karimialavijeh; emergency department, dr. shariati hospital, kargar ave, tehran, iran. p.o box: 14117-13137, tel: +982161192240 fax: +982166904848, e-mail: e-karimi@sina.tums.ac.ir despite continuous training and education, even trained healthcare providers may perform suboptimal cpr (2). according to the cpr quality consensus statement released by the american heart association (aha), cpr quality should be monitored during all resuscitations (3). the relevant metrics include parameters such as chest compression rate and depth, ventilation rate, compression pause duration, and incomplete chest recoil (4). the quality of cpr has many aspects including team management, patient management, utilizing standard medical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. afzalimoghaddam et al. 2 devices (cardiac monitors, electroshock devices, etc.) and performing the process of cpr based on the latest guidelines recommended by the aha (5). a system for measuring the quality of cpr should be part of any hospital’s safety protocol. in order to control the quality of cpr in the ed, investigators need to use a checklist containing all aspects of high-quality cpr. furthermore, ed has different specifications compared with other parts of the hospital. overcrowding, lack of resources and teamwork have a negative impact on medical care in eds, including cpr (6). based on abovementioned points, the present study aimed to invite a group of medical specialists in the field of resuscitation to review the current resuscitation guidelines in the literature and generate a user-friendly checklist for quality control of cpr in the ed. 2. methods 2.1. study design and setting this was a qualitative study performed between january and december 2018. the current literature was searched for preferred items regarding cpr quality control; then using the focus discussion and delphi panel, a cpr quality control checklist was developed. the local ethics committee of the tums approved the conduct of the study, and all patient data were protected with respect to patients’ privacy (ethics code: 42851300297.). 2.2. data gathering in the first step, two emergency medicine specialists searched currently available databases (ovid, pubmed, medscape, google scholar, web of science, and scopus) and extracted the factors related to cpr quality (table 1). we used a broad search strategy to identify studies assessing the quality of cpr in emergency department. the search strategy included medical subject headings and keywords related to "cardiopulmonary resuscitation", "heart arrest", "quality control", "and emergency medicine". afterwards, two sessions of focus group discussions were held. the duration of each session was two hours. a group of medical specialists, consisting of four emergency medicine specialists, two ed managers, one anesthesiologist, and one cardiologist, participated in the focus group discussions. the participants were all faculty members of tehran university of medical sciences (tums) with at least five years of professional experience in the field of emergency medicine and resuscitation or ed management. the discussion aimed to reach at least a 90% consensus about each extracted factor. subsequently, another 20 medical specialists, consisting of 10 emergency medicine specialists, six anesthesiologists, and four cardiologists, were invited to a delphi panel. they rated the items derived from the prior focus group discussions in order to reach at least 75% agreement for each item. a likert scale (between 0 for strongly disagree and 5 for strongly agree) was used to rate the items. these items were selected to generate a checklist for quality control of cpr in ed. this checklist was piloted in a university-affiliated urban ed for three months assessing 70 cardiac arrest patients and adjustments were made by a team of medical specialists, including four emergency medicine specialists, one cardiologist, and one anesthesiologist. eventually, a checklist for quality control of cpr in ed was prepared. 2.3. statistical analysis the inter-rater agreement for each item among medical specialists was analyzed using the kappa statistic (k), where k greater than 0.75 was considered as complete agreement (7). data analysis was performed using spss (version 22, spss inc., chicago, il). table 1: factors related to high-quality cardiopulmonary resuscitation (cpr) in the literature factors post cpr survival rate before hospital discharge rate of return of spontaneous circulation (rosc) chest compression depth chest compression rate compression-ventilation ratio cpr duration delay to initiate cpr initial cardiac rhythm brain function after rosc 3. results: the flow chart of the study is depicted in figure 1. after a literature review by two emergency medicine specialists, factors related to cpr quality were extracted and summarized into nine categories (table 1). during two rounds of focus group discussions, 38 items related to the quality of cpr were identified in order to formulate a checklist. the items on this primary checklist were evaluated by a delphi panel; 31 items with at least 75% agreement were selected. these 31 items were included in the final checklist and sorted into ten categories after a pilot study and adjustment of its content (table 2). 4. discussion maintaining high-quality cpr in the ed requires monitoring and feedback. suboptimal cpr is reported among healthcare providers; there are also reports about the decline in the quality of cpr after transferring the care of victims from a prehospital setting to the ed (1). in this study, a group of specialthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e61 figure 1: the flow chart of the study. ists in the field of resuscitation and emergency medicine participated in two rounds of group discussions and one delphi panel to reach a consensus on quality control of cpr in the ed. eventually, 31 factors were identified and classified into ten categories. these 31 items were used to generate a checklist for quality control of cpr in the ed. based on aha guidelines, the rate of chest compression in cpr is 100-120/min (2, 8, 9). since any pause in chest compression has a massive negative impact on the outcome of cpr, this factor plays a crucial role in performing high-quality cprs (10). compression depth is an essential part of high-quality cpr and has been deemed related to patient survival (4, 11). while the recommended depth of chest compression in adults is 2 inches, stiell et al. reported that there is no strict depth for chest compression (12). furthermore, measuring the depth of chest compression needs equipment such as an accelerometer or impulse-radio ultra-wideband (iruwb) sensor (13). in a resource-limited ed, as is often the case in our country, these devices are not available, and the precise measurement of the depth of chest compression is not possible. our participants emphasized the necessity for advanced devices. nevertheless, our specialists arrived at a strong consensus about this item, and we included chest compression depth in our checklist. cha et al., in 2015, reported that cpr for less than 20 min significantly decreases the survival of patients with cardiac arrest (14). there are many factors that impact the duration of cpr, including patients’ age, past medical history, prognosis of the current illness, and time of arrest (15). we could not identify any specific duration for cpr in our study. we did not define different weights for our items. however, these items have different values, and we need to undertake more research to define a weight for each item. moreover, there are other factors that impact the quality of medical care in ed, including cpr, such as overcrowding, lack of resources, and burnout and occupational stress among personnel (6). in order to maintain high-quality cpr, all these factors must be considered and resolved. if survival rates and neurologic outcomes in cardiac arrests in eds are to be improved, it is crucial that ed staff understand all aspects of high-quality cpr. in conclusion, our study provides a checklist for monitoring the quality of cpr in the ed, but it is still necessary to include other factors related to the ed environment in this checklist. 5. conclusion our study provides a checklist for monitoring the quality of cpr in the ed, but it is still necessary to include other factors related to the ed environment on this checklist. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. afzalimoghaddam et al. 4 table 2: items (checklist) for monitoring cardiopulmonary resuscitation (cpr) quality category/items agreement* chest compression put hands on the lower third of the sternum in the midline. 0.8 compression depth at least 2 inches for adults. 1 allow complete chest recoil after each compression. 1 compression rate 100-120/minute. 1 change compressor after 2 minutes with minimum delay. 0.95 airway open airway properly. 0.9 bag-mask ventilation proper mask seal. 0.78 proper mask holding by the rescuer. 0.82 keep compression-ventilation ratio at 30:2. 1 insert oral airway. 0.76 deliver each breath in one second. 0.86 cardiac monitoring initiate cardiac monitoring immediately. 0.78 proper diagnosis of cardiac rhythm. 0.9 proper pulse check in 10 seconds. 0.92 defibrillation set shock energy properly. 0.96 put paddles in proper position. 0.9 insert sufficient pressure on paddles. 0.77 warn the cpr team to be clear of the patient before shock delivery. 1 continue the massage immediately after shock delivery. 1 iv drug delivery deliver drugs at a proper time based on the cardiac rhythm. 0.98 provide iv access (peripheral, central, intra-osseous, and cutdown). 0.95 medications choose drugs based on correct indications. 1 proper drug dosage. 0.95 advanced airway provide advanced airway. 0.96 minimum delay in cardiac massage when inserting the airway. 1 correctly confirm the location of the airway. 1 proper ventilation rate and volume. 0.96 use 100% oxygen. 0.8 cpr sequence stick to the proper sequence of the aha algorithms. 1 reversible causes consider reversible causes. 0.97 use proper interventions to resolve reversible causes. 0.95 *based on cohen’s kappa coefficient. iv: intravenous; aha: american heart association. 6. appendix 6.1. acknowledgements we thank our colleagues and the medical staff of emergency medicine department of imam khomeini hospital, who greatly assisted in research. 6.2. author contribution study design: afzalimoghaddam m, data collection and analysis: zakipour g, mirfazaelian h, and nejati a, manuscript writing: karimialavijeh e and payandemehr p. authors orcids mohammad afzalimoghaddam: 0000-0002-3512-4746 karimialavijeh ehsan: 0000-0003-0814-9048 amir nejati: 0000-0001-9248-8768 zakipour gholamreza: 0000-0003-2373-5096 hadi mirfazaelian: 0000-0001-9299-8928 pooya payandemehr: 0000-0003-3556-4052 6.3. funding the authors received no specific funding for this work. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e61 6.4. conflict of interest the authors have declared that there is no conflict of interest. references 1. crowe c, bobrow bj, vadeboncoeur tf, dameff c, stolz u, silver a, et al. measuring and improving cardiopulmonary resuscitation quality inside the emergency department. resuscitation. 2015;93:8-13. 2. losert h, sterz f, kohler k, sodeck g, fleischhackl r, eisenburger p, et al. quality of cardiopulmonary resuscitation among highly trained staff in an emergency department setting. archives of internal medicine. 2006;166(21):2375-80. 3. meaney pa, bobrow bj, mancini me, christenson j, de caen ar, bhanji f, et al. cardiopulmonary resuscitation quality: improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the american heart association. circulation. 2013;128(4):417-35. 4. talikowska m, tohira h, finn j. cardiopulmonary resuscitation quality and patient survival outcome in cardiac arrest: a systematic review and meta-analysis. resuscitation. 2015;96:66-77. 5. wallace sk, abella bs, becker lb. quantifying the effect of cardiopulmonary resuscitation quality on cardiac arrest outcome: a systematic review and metaanalysis. circulation: cardiovascular quality and outcomes. 2013;6(2):148-56. 6. farahmand s, karimialavijeh e, vahedi hsm, jahanshir a. emergency medicine as a growing career in iran: an internet-based survey. world journal of emergency medicine. 2016;7(3):196. 7. mcevoy md, smalley jc, nietert pj, field lc, furse cm, blenko jw, et al. validation of a detailed scoring checklist for use during advanced cardiac life support certification. simulation in healthcare: journal of the society for simulation in healthcare. 2012;7(4):222. 8. idris ah, guffey d, aufderheide tp, brown s, morrison lj, nichols p, et al. relationship between chest compression rates and outcomes from cardiac arrest. circulation. 2012;125(24):3004-12. 9. idris ah, guffey d, pepe pe, brown sp, brooks sc, callaway cw, et al. chest compression rates and survival following out-of-hospital cardiac arrest. critical care medicine. 2015;43(4):840-8. 10. cheskes s, schmicker rh, verbeek pr, salcido dd, brown sp, brooks s, et al. the impact of peri-shock pause on survival from out-of-hospital shockable cardiac arrest during the resuscitation outcomes consortium primed trial. resuscitation. 2014;85(3):336-42. 11. sutton rm, french b, niles de, donoghue a, topjian aa, nishisaki a, et al. 2010 american heart association recommended compression depths during pediatric inhospital resuscitations are associated with survival. resuscitation. 2014;85(9):1179-84. 12. stiell ig, brown sp, christenson j, cheskes s, nichol g, powell j, et al. what is the role of chest compression depth during out-of-hospital cardiac arrest resuscitation? critical care medicine. 2012;40(4):1192. 13. yu bg, oh jh, kim y, kim tw. accurate measurement of chest compression depth using impulseradio ultra-wideband sensor on a mattress. plos one. 2017;12(8):e0183971. 14. cha wc, lee ej, hwang s-s. the duration of cardiopulmonary resuscitation in emergency departments after out-of-hospital cardiac arrest is associated with the outcome: a nationwide observational study. resuscitation. 2015;96:323-7. 15. stub d, bernard s, pellegrino v, smith k, walker t, sheldrake j, et al. refractory cardiac arrest treated with mechanical cpr, hypothermia, ecmo and early reperfusion (the cheer trial). resuscitation. 2015;86:88-94. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e71 or i g i n a l re s e a rc h diagnostic value of erythrocyte sedimentation rate and c reactive protein in detecting diabetic foot osteomyelitis; a cross-sectional study seyed kaveh moallemi1, mahtab niroomand2, niki tadayon3, mohammad mehdi forouzanfar4, alireza fatemi5∗ 1. aja university of medical sciences, tehran, iran. 2. division of endocrinology, department of internal medicine, shahid beheshti university of medical sciences, tehran, iran. 3. surgery department, shahid beheshti university of medical sciences, tehran, iran. 4. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 5. men’s health and reproductive health research center, shahid beheshti university of medical sciences, tehran, iran. received: june 2020; accepted: august 2020; published online: 8 september 2020 abstract: introduction: osteomyelitis is one of the complications of diabetic foot infection. the present study aimed to evaluate the diagnostic value of erythrocyte sedimentation rate (esr) and c reactive protein (crp) in detection of osteomyelitis in patients with diabetic foot. methods: in this cross-sectional study, serum levels of esr and crp were measured for patients with diabetic foot referring to emergency department or endocrinology clinic and the screening performance characteristics of these markers in detection of osteomyelitis were calculated. the diagnosis of osteomyelitis was based on clinical examination and positive probe-to-bone test, which was confirmed by plain x-rays or mri. results: 142 diabetic patients with an average age of 61.2 ± 11.8 years were evaluated (66.2% male). the area under the roc curve of esr in detection of osteomyelitis in diabetic foot cases was 0.70 (95% ci: 0.62-0.79). the best esr cut-off point in this regard was 49 mm/hour. sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of esr in 49 mm/hour cut-point were 74.6% (95% ci: 62.9-83.9), 57.7% (95% ci: 45.5-69.2), 63.9% (95% ci: 52.5-73.9), 69.5% (95% ci: 56.0-80.0), 1.8 (95% ci: 1.3-2.4) and 0.4 (95% ci: 0.3-0.7), respectively. the area under the roc curve of crp in detection of osteomyelitis was 0.67 (95% ci: 0.58-0.76). the best cut-off point for crp in this regard was 35 mg/liter with sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of 76% (95% ci: 64.2-85), 54.9% (95% ci: 42.7-66.6), 62.8% (95% ci: 51.6-72.8), 69.6% (95% ci: 51.7-80.8), 1.7 (95% ci, 1.3-2.2), and 0.4 (95% ci: 0.3-0.7), respectively. conclusion: based on the findings of roc curve analysis, esr and crp had fair and poor accuracy, respectively, in detecting the diabetic foot cases with osteomyelitis. keywords: c-reactive protein; diabetic foot; blood sedimentation; osteomyelitis cite this article as: moallemi s k, niroomand m, tadayon n, forouzanfar m m, fatemi a. diagnostic value of erythrocyte sedimentation rate and c reactive protein in detecting diabetic foot osteomyelitis; a cross-sectional study. arch acad emerg med. 2020; 8(1): e71. 1. introduction more than 50% of non-traumatic amputations in the united states are lower-extremity amputations due to diabetes mellitus (1). about 5% of diabetic persons are facing foot ulcers ∗corresponding author: alireza fatemi; men’s health and reproductive health research center, shohadaye tajrish hospital, shahrdary avenue, tajrish square, tehran, iran. phone: 00989128949858, fax: 00982122719014, email: alireza.fatemi.md@gmail.com. each year and treatment of foot ulcers accounts for 15-25% of total health care processes for diabetes (2, 3). chronic and deep wounds can get complicated by osteomyelitis as a consequence of contiguous spread of the microorganisms from soft tissues to periosteum, and that is the main cause of amputation in the majority of these patients (4). timely diagnosis of osteomyelitis is important for preventing migration of the infection, and delay in osteomyelitis wound treatment leads to recurrent foot ulcers, increases the likelihood of need for surgical intervention and amputation, and elongates the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s k. moallemi et al. 2 duration of antibiotic therapy (5, 6). several different options, including computed tomography (ct) scan, magnetic resonance imaging (mri), and triple-phase bone scans, with different degrees of sensitivity and specificity, have been introduced for use in diagnosis of osteomyelitis (7), but some studies have revealed that such imaging modalities were not cost-effective and, therefore, suggested that clinical signs of infection coupled with the findings of the wound probing to bone can be much more cost-effective for this purpose (8). increased serum inflammatory markers such as white blood cells (wbcs), c-reactive protein (crp), and erythrocyte sedimentation rate (esr) have been proposed to aid in diagnosis of osteomyelitis. however, in patients with diabetes, their value in the presence of infection has been questioned (9, 10). the aim of this study was to determine the diagnostic accuracy of esr and crp in detection of diabetic foot cases with osteomyelitis. 2. methods 2.1. study design and setting in this cross-sectional study, after receiving the ethics approval (ethics code: ir.sbmu.retech.rec.1396.540) and patient informed consent, all patients who met the american diabetes association criteria (11) for diagnosis of diabetes mellitus and had diabetic foot, and had presented to the emergency department or endocrinology clinic of shohadaye tajrish hospital, tehran, iran, from april 2018 to 2019 were evaluated. 2.2. participants using convenience sampling, all >18 years old patients with diabetic foot were enrolled. patients were excluded if they had any other concurrent infections, non-infectious inflammatory disease, or rheumatologic diseases. patients who received immunosuppressive therapy and pregnant cases were also excluded. 2.3. data gathering using a predefined checklist, age, gender, leukocyte count, serum level of esr or crp, the characteristics of the wound (bone visibility, positive probe test, dactylitis, wounds remaining more than four weeks, or septic secretions for more than two weeks), as well as presence or absence of osteomyelitis were registered for all cases. the diagnosis of osteomyelitis was based on clinical examination and positive probe-to-bone test and it was confirmed by plain x-rays or mri (6). six milliliter of peripheral blood sample was drawn from each individual and inserted into a vial containing ethylenediamine tetraacetic ethylenediaminetetraacetic acid (edta) anticoagulant. blood samples were collected under aseptic conditions from an antecubital vein for determination of white blood cell (wbc) count and esr using the modified westergren method. serum crp was measured using bn prospec system (siemens healthcare diagnostic products gmbh, marburg, germany; interand intra-assay coefficient of variation <4%). 2.4. statistical analysis data were analyzed using statistical package for the social sciences (spss) version 16 (spss inc. chicago, il) for windows. data were presented as mean ± standard deviation or frequency and percentage. the area under the receiver operating characteristic (roc) curve was used to determine the best cut-off point of studied markers in detecting osteomyelitis. p value of less than 0.05 was considered statistically significant. accuracy of 90% 100% was considered as excellent, 80% – 90% as good, 70% – 80% as fair, 60% – 70% as poor and < 60% as fail. 3. results 3.1. baseline characteristics of studied cases a total of 142 diabetic patients with an average age of 61.2 ± 11.8 years were evaluated (66.2 % male). the diagnosis of osteomyelitis was confirmed for 71 (50.0%) cases. the mean age of patients with and without osteomyelitis was 59.7 ± 11.5 and 62.7 ± 11.9 years, respectively (p = 0.12). table 1 compares the baseline characteristics of patients with and without osteomyelitis. the frequency of open wound during the previous 4 weeks (64.8%; p = 0.03), presence of discharge during the last 2 weeks (47.9%; p <0.0001), and the prevalence of smoking (28.2%; p = 0.02) were significantly higher in osteomyelitis cases. serum esr levels were 71.2 ± 29.8 and 50.8 ± 24.5 (mm/ hour) in cases with and without osteomyelitis, respectively (p < 0.0001). these measures were 65.8 ± 37.2 and 43.6 ± 33.0 (mg/liter), respectively, for crp level (p = 0.0002). the number of white blood cells was significantly higher in the osteomyelitis group (p = 0.005). 3.2. the diagnostic values of esr and crp area under the roc curve of esr in detection of osteomyelitis in diabetic foot cases was 0.70 (95% ci: 0.62-0.79; figure 1). the best esr cut-off point in this regard was 49 mm/hour. the sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of esr in 49 mm/hour cut-point were 74.6% (95% ci: 62.9-83.9), 57.7% (95% ci: 45.5-69.2), 63.9% (95% ci: 52.5-73.9), 69.5 % (95% ci: 56.0-80.0), 1.8 (95% ci: 1.3-2.4) and 0.4 (95% ci: 0.3-0.7), respectively. area under the roc curve of crp in detection of osteomyelitis was 0.67 (95% ci: 0.58-0.76; figure 1). the best cut-off this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e71 table 1: comparing the characteristics of studied patients between cases with and without osteomyelitis variables suffering from osteomyelitis p without n = 71 with n = 71 smoking 9(12.7%) 20(28.2%) 0.02 open wound in last 4 weeks 33(46.5%) 46(64.8%) 0.03 discharge during last 2 weeks 7(9.9%) 34(47.9%) < 0.0001 visible bone 0(0%) 2(2.8%) 0.49 atherosclerosis 35(49.3%) 31(43.7%) 0.50 hypertension 36(50.7%) 40(56.3%) 0.50 hyperlipidemia 15(21.1%) 20(28.2%) 0.33 data are presented based on frequency (%). figure 1: the area under the receiver operating characteristic (roc) curve of erythrocyte sedimentation rate (left) and c reactive protein (right) in detecting the diabetic foot cases with osteomyelitis. point for crp in this regard was 35 mg/liter with sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of 76% (95% ci: 64.2-85), 54.9% (95% ci: 42.7-66.6), 62.8% (95% ci: 51.6-72.8), 69.6% (95% ci: 51.7-80.8), 1.7 (95% ci, 1.3-2.2), and 0.4 (95% ci: 0.30.7), respectively. 4. discussion based on the findings of roc curve analysis the esr and crp had fair and poor accuracy, respectively, in detecting diabetic foot cases with osteomyelitis. an infected bone in patients with diabetic foot ulcers causes major clinical complication and increases the risk of surgical procedures and lower extremity amputations and also increases the probability of treatment outcomes like antibiotic resistance, kidney injury and catheter-related adverse events, which limit options for treatment and therapy and worsen the prognosis for cure (12-14). in spite of these potentially devastating consequences, most treatment options are based on experience and advice, due to lack of high-quality evidence. the findings of this study showed that the predictive value of esr and crp in detecting osteomyelitis is desirable. the sensitivity and specificity for esr and crp were 74.6%, 57.7% and 76%, 54.9%, respectively. the value of each of these biomarkers is significantly less than mri. kaleta et al. (15) found that erythrocyte sedimentation rate was significantly higher in the presence of underlying bone infections. in addition, they determined the optimal cut-off value with the highest positive and negative predictive values as 70 mm/h. these finding confirm the role of esr in prediction of osteomyelitis in diabetic patients; however, the best esr cut-off point to predict osteomyelitis, was 49 mm per hour in the current study. most previously published studies have failed to assess the relationship between esr and presence of osteomyelitis or have not specifically studied its use in the diabetic population, while many of them have stated that elevation in esr is a predictor of the presence of osteomyelitis (16-18). the results of asten et al. study suggested a predictive role for both esr and crp at the time of monitoring the success of therapy in diabetic foot osteomyelitis (12). the sensitivity this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s k. moallemi et al. 4 and specificity of crp (cut-off value >14 mg/l) in diagnosis of osteomyelitis were 0.85 and 0.83. these values were 0.84 and 0.75 for esr (cut-off value > 67 mm/h), 0.75 and 0.79 for wbc (cut-off value >14 × 109/l), and 0.81 and 0.71 for pct (cutoff value >0.30 ng/ml), respectively, in michail et al. study (2). although there are some differences in values, but that study, like the present study, showed that serum inflammatory markers including crp, esr and wbc could be used for the diagnosis of foot infections in patients with diabetes. based on the oktay yapäścäś et al. study (19), neutrophilto-lymphocyte ratio, crp, and esr have a predictive value for development of osteomyelitis and progression to amputation in patients with diabetic foot osteomyelitis. as can be seen, all of the mentioned studies have reported a significant relationship between inflammatory markers and osteomyelitis. however, the reported diagnostic values for these markers vary between studies, with sensitivity ranging from 75% to 90% and specificity ranging from 70% to 80%. the findings of this study showed that on average, the values of all inflammatory markers, including esr and crp, show an increase in patients with diabetic foot infections and higher values were found in patients with osteomyelitis. 5. limitations limitations of this investigation include the small number of cases reviewed. in future investigations, a prospective evaluation, in which all patients with osteomyelitis are confirmed with pathology, would improve the value of the study. in addition, the authors did not correlate location of the bone involvement with laboratory values. it may prove that the presence of infection in highly vascular areas of the foot or body may affect the sedimentation rate. 6. conclusion based on the findings of roc curve analysis, esr and crp had fair and poor accuracy, respectively, in detecting the diabetic foot cases with osteomyelitis. 7. declarations 7.1. acknowledgements hereby, we thank the staff members of shohadaye tajrish hospital for their hearty cooperation and helping us perform this study. 7.2. author contribution all the authors met the 4 criteria recommended by the international committee of medical journal editors for gaining authorship. 7.3. funding/support none. 7.4. conflict of interest all authors declare that they have no conflict of interest. references 1. pecoraro re, reiber ge, burgess em. pathways to diabetic limb amputation: basis for prevention. diabetes care. 1990;13(5):513-21. 2. michail m, jude e, liaskos c, karamagiolis s, makrilakis k, dimitroulis d, et al. the performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. the international journal of lower extremity wounds. 2013;12(2):94-9. 3. abegunde do, mathers cd, adam t, ortegon m, strong k. the burden and costs of chronic diseases in lowincome and middle-income countries. the lancet. 2007;370(9603):1929-38. 4. lipsky ba, moran gj, napolitano lm, vo l, nicholson s, kim m. a prospective, multicenter, observational study of complicated skin and soft tissue infections in hospitalized patients: clinical characteristics, medical treatment, and outcomes. bmc infectious diseases. 2012;12(1):227. 5. lipsky ba. a report from the international consensus on diagnosing and treating the infected diabetic foot. diabetes/metabolism research and reviews. 2004;20(s1). 6. lipsky ba, berendt ar, cornia pb, pile jc, peters ej, armstrong dg, et al. 2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections a. clinical infectious diseases. 2012;54(12):e132-e73. 7. wrobel js, connolly j. making the diagnosis of osteomyelitis. the role of prevalence. journal of the american podiatric medical association. 1998;88(7):337-43. 8. grayson ml, gibbons gw, balogh k, levin e, karchmer aw. probing to bone in infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients. jama. 1995;273(9):721-3. 9. leichter sb, allweiss p, harley j, clay j, kupersteinchase j, sweeney gj, et al. clinical characteristics of diabetic patients with serious pedal infections. metabolism. 1988;37(2):22-4. 10. armstrong dg, lavery la, sariaya m, ashry h. leukocytosis is a poor indicator of acute osteomyelitis of the foot in diabetes mellitus. the journal of foot and ankle surgery. 1996;35(4):280-3. 11. association ad. diagnosis and classification of diabetes mellitus. diabetes care. 2014;37(supplement 1):s81-s90. 12. asten sa, jupiter dc, mithani m, la fontaine j, davis ke, lavery la. erythrocyte sedimentation rate and câăřrethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e71 active protein to monitor treatment outcomes in diabetic foot osteomyelitis. international wound journal. 2017;14(1):142-8. 13. lavery la, peters ej, armstrong dg, wendel cs, murdoch dp, lipsky ba. risk factors for developing osteomyelitis in patients with diabetic foot wounds. diabetes research and clinical practice. 2009;83(3):347-52. 14. lipsky ba, itani k, norden c, group ldfis. treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillinsulbactam/amoxicillin-clavulanate. clinical infectious diseases. 2004;38(1):17-24. 15. kaleta jl, fleischli jw, reilly ch. the diagnosis of osteomyelitis in diabetes using erythrocyte sedimentation rate: a pilot study. journal of the american podiatric medical association. 2001;91(9):445-50. 16. carragee ej, kim d, van der vlugt t, vittum d. the clinical use of erythrocyte sedimentation rate in pyogenic vertebral osteomyelitis. spine. 1997;22(18):2089-93. 17. jones n, anderson d, stiles p. osteomyelitis in a general hospital. a five-year study showing an increase in subacute osteomyelitis. bone & joint journal. 1987;69(5):77983. 18. lewis vl, bailey mh, pulawski g, kind g, bashioum rw, hendrix rw. the diagnosis of osteomyelitis in patients with pressure sores. plastic and reconstructive surgery. 1988;81(2):229-32. 19. yapäścäś o, berk h, ãűztoprak n, seyman d, tahmaz a, merdin a. can ratio of neutrophil-to-lymphocyte count and erythrocyte sedimentation rate in diabetic foot infecti on predict osteomyelitis and/or amputation? hematology reports. 2017;9(1). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e68 rev i ew art i c l e comparison of ketamine and tramadol in management of acute pain; a systematic review bahman naghipour1, mahboub pouraghaei2, ali tabatabaey3, allahveirdy arjmand4, gholamreza faridaalaee5,2∗ 1. department of anesthesiology and critical care, tabriz university of medical sciences, tabriz, iran. 2. emergency medicine research team, faculty of medicine, tabriz university of medical sciences, tabriz, iran. 3. department of emergency medicine, amiralmomenin hospital, islamic azad university-tehran medical branch, tehran, iran. 4. department of anesthesiology, maragheh university of medical sciences, maragheh, iran. 5. department of emergency medicine, maragheh university of medical sciences, maragheh, iran. received: june 2020; accepted: july 2020; published online: 23 august 2020 abstract: introduction: management of pain is an important part of care in the emergency department (ed). tramadol and ketamine have both been introduced as alternatives to opioids in the ed and post-operative setting. in this study, we conducted a systematic review of available literature to compare the analgesic efficacy, and side effect profile of these two medications in management of severe acute pain. methods: this is a systematic review based on the prisma protocol. in this study, peer-reviewed papers published by march 3, 2020, which compared analgesic effects of tramadol and ketamine in management of acute pain were included. results: the initial search of online databases identified 2826 non-duplicate records. finally, three papers available in full text were analyzed for study quality. the results show that ketamine has consistently been shown to be superior to tramadol for pain control and causes fewer significant side effects. conclusion: results of this review show that low-dose ketamine is more effective than tramadol in pain control, while causing fewer side effects. keywords: ketamine; tramadol; pain management; emergency treatment; acute pain cite this article as: naghipour b, pouraghaei m, tabatabaey a, arjmand a, faridaalaee gh. comparison of ketamine and tramadol in management of acute pain; a systematic review. arch acad emerg med. 2020; 8(1): e68. 1. introduction pain is one of the most common patient complaints in the emergency department (ed), and management of pain is an important part of care in the ed (1). multicenter studies have reported that up to 78% of patients admitted to ed complain of acute pain (1). pain control has been considered a human right (2) and in 2011, analgesics were administered in 97 million ed visits (3). many medications are used as analgesics for acute pain; examples include opioids, non-steroidal antiinflammatory drugs, acetaminophen, ketamine, and duloxetine (4-8). educational campaigns in the 1990s focused on systematic assessment and treatment of pain (9). a perfect ∗corresponding author: gholamreza faridaalaee; department of emergency medicine, maragheh university road, maragheh university of medical sciences, maragheh, iran. email: faridaalaee@tbzmed.ac.ir, grf.aalae@yahoo.com, tel: +98-4137276363 analgesic is one with quick onset, no side effects, and an extended effect. since, such a medication has yet to be discovered strategies such as "analgesic pyramid", "balanced analgesia" and "channels-enzymes-receptors targeted analgesia" have emerged (10). in the analgesic pyramid, medication is chosen based on severity of pain. yet, for severe pain, treatment options are limited and opioids are the most common analgesic used (9), despite their unfavorable adverse effect profile, including respiratory depression, dependence, and risk of overdose. in canada, one in every 550 people who are started on opioids die (11), and death from an opioid overdose is an important cause of death in the 18 to 35 age group (11, 12). therefore, clinicians are looking at safer alternatives for the management of severe pain in the postoperative and ed settings. tramadol is considered an atypical opioid with multiple effects on various receptors (13, 14). it has shown efficacy in reducing different types of pain and is less likely to cause dependence than opioids. its adverse effect profile is different this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. naghipour et al. 2 from opioids and is less likely to cause respiratory depression but more likely to induce seizures (7, 13, 15-17). in recent years, ketamine has gained popularity as a sedative and analgesic in the ed. ketamine is a phencyclidine derivative, which is a dissociative sedative and an amnestic in addition to having analgesic properties (6). it has also been found to have fast acting antidepressant effects (18). it can easily be administered through oral, intranasal, rectal, intramuscular, or intravenous routes. it has rapid onset and a wide window of effects without the risk of respiratory depression, which makes it an attractive choice for management of acute pain. yet fear of other side effects, such as increased intracranial pressure, increased cardiovascular load, and emergence reactions, has limited its use (19-22). ketamine and tramadol both have advantages and disadvantages, so in this study we decided to systematically review available literature to compare the analgesic efficacy, and side effect profile of these two medications in management of severe pain. 2. methods 2.1. study design this is a systematic review based on the prisma protocol (23). the study pico is: population of patients with severe acute pain in the ed or postoperative setting, intervention is ketamine, intravenously, compared with tramadol, and the outcome is control of acute pain. secondary outcome is the prevalence of side effects. 2.2. eligibility criteria in this study, peer-reviewed papers published by march 3, 2020, which compared analgesic effects of tramadol and ketamine for in management of acute pain were included. intravenous administration of ketamine and tramadol was an inclusion criteria and other routes of administration, such as nasal or epidural routes, were excluded from the study. for papers that were only available as abstracts, multiple attempts were made to contact the authors using available means (emails, social media, researchgate, etc.). unfortunately, we were not able to secure full text versions for abstracts presented in seminars. 2.3. search strategy relevant search items and keywords for the study question were selected from mesh and emtree terms after consulting an emergency medicine specialist and an anesthesiologist. a literature search was conducted via electronic resources including medline, web of science, embase, and central cochrane library up to the march 3, 2020. references of found papers were also searched for relevant studies. the search strategy in medline followed the pattern described in table 1. 2.4. study selection, data collection, and outcome measurement initially, all the studies found, which evaluated effects of ketamine and tramadol in management of acute pain, were included. abstracts of all papers were reviewed by two members of the research team and papers were further screened based on inclusion and exclusion criteria described above. relevant papers were then reviewed in full text and those meeting the criteria were included in the study. their findings were then summarized and evaluated using standardized checklists and study quality was assessed by two members of the research team, independently. any discrepancy between the reviews was resolved either through discussion or a verdict by a third researcher. in this systematic review, the primary outcome was analgesic efficacy of tramadol and ketamine, described through decrease in pain score or necessity of a second analgesic. secondary outcome was prevalence of adverse effects among patients receiving tramadol and ketamine. 2.5. statistical analysis descriptive analysis was performed on data. all included studies were summarized and categorized based on predefined variables. 3. results 3.1. study selection and study characteristics the initial search of online databases identified 2826 nonduplicate records. after screening of abstracts, 2813 studies were eliminated. thirteen papers were assessed in full text. five were found to be ineligible for the study. four studies were presentation abstracts and attempts were made to contact authors in order to obtain them in full text without success (24-27). two of the presentations consisted of similar findings (26, 27). one paper was only available in abstract form and the author did not respond to researchers (28). therefore, only three papers, available in full text, were analyzed for study quality (29-31). due to the paucity of eligible studies, the authors decided to include findings from the presentation abstracts with relevant findings in this systematic review. figure 1 summarizes the selection process. specifications and characteristics of included studies are reported in table 2. overall, 257 patients were evaluated for analgesic effects of ketamine and tramadol in acute pain. 3.2. quality control of study and risk of bias the quality of included studies was evaluated, and results are summarized in table 3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e68 table 1: medline search strategy database search terms medline (pubmed) 1) ketamine or ketalar or ketaset or ketanest or calipsol or kalipsol or calypsol or ketamine hydrochloride or esketamine 2) tramadol or tramundin or biodalgic or jutadol or mtw-tramadol or mtw tramadol or mtwtramadol or nobligan or prontofort or zytram or takadol or theradol or tiral or tramadol lindo or topalgic or tradol or tradol-puren or tradol puren or tradolpuren or tradonal or tralgiol or trama abz or trama kd or trama-dorsch or trama dorsch or tramadorsch or biokanol or tramabeta or tramadin or tramadol-ratiopharm or tramadolratiopharm or tramadol ratiopharm or tramadoc or tramadol pb or tramadol acis or tramadol al or tramadol basics or tramadol bayvit or tramadol bexal or tramadol 1a or ranitidin 1a pharma or trama 1a pharma or tramadol cinfa or tramadol edigen or tramadol hydrochloride or trasedal or ultram or tramadol heumann or xymel 50 or zamudol or zumalgic or zydol or tramadol kern or tramadol lichtenstein or tramadol mabo or tramadol normon or tramadol stada or tramadol-dolgit or tramadol dolgit or tramadoldolgit or tramadol-hameln or tramadol hameln or tramadolhameln or tramadolor or tramadura or tramagetic or tramagit or tramake or tramal or tramex or adolonta or contramal or amadol or tramadol asta medica 3) 1 &2 table 2: characteristics of included studies author ketamine group tramadol group n age male dose n age male dose khajavi 2016 40 46.93 29 0.5 mg/kg 40 42.17 25 0.7 mg/kg burimsittichai 2016 70 47 14 0.5 mg/kg 67 44 12 1.5 mg/kg yu c 2005 20 44.67 14 0.5 mg/kg 20 47.33 9 0.3 mg/kg kilinc y 2018 16 7-21 10 ketamine (0.25 mg/ kg/ dose) 31 6-21 16 tramadol (0.1-0.4 mg /kg/ h) zghidi 2011 20 adult 0.2mg/kg, +2µ/kg/min 20 adult 100 mg + 0.5 mg/kg and 0.1mg/kg/h table 3: risk of bias assessment of included studies based on nhlbi tools variable khajavi burimsittichai yu c publication in peer-reviewed journal © © © sample size calculation © © ? description of group and intervention © © § description of control group © © § exclusion criteria © © © randomization © © © blinding © © ? ethical approval ? © © informed consent © © ? specified main outcome © © © specified secondary outcome © © © description of statistical analysis © © © statement of conflict of interest § © § high risk of bias: §, low risk of bias: © 3.3. analgesic effect systematic review of results shows that analgesic effects of low-dose ketamine (0.25-0.5 mg/kg) are significantly larger/stronger than tramadol (0.3-1.5 mg/kg). khajavi et al. looked at 80 patients with acute pain following renal surgery in a double blind randomized controlled study (29). one group received intravenous paracetamol plus ketamine and the other received intravenous paracetamol plus tramadol. they found that patients who received ketamine had significantly lower pain scores compared to those who received tramadol. in the study by burimsittichai et al. 207 patients with pain secondary to foley catheters in the postoperative setting were randomly allocated to a group in a double blind randomized clinical trial (rct) to receive either ketamine 0.5mg/kg or tramadol 1.5mg/kg, or placebo (30). analgesic effects were compared 6 and 24 hours after this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. naghipour et al. 4 figure 1: prisma diagram of systematic review. laparoscopic surgery. the authors reached the conclusion that use of either medication significantly reduces pain, compared to placebo, but did not compare these groups to one another. although the group receiving ketamine appeared to have lower pain scores, the statistical significance of this observation was not discussed by the authors. yu c. and colleagues studied patients suffering from postoperative hyperalgesia and also found that those receiving intravenous ketamine had significantly better pain control compared to those receiving tramadol (31). kilinc and colleagues in their study looked at patients with sickle cell anemia, aged 6 years and over, suffering from acute pain episodes (25). one group received ketamine and the other received tramadol. results showed that ketamine was more effective that tramadol in controlling pain. alp reported using either ketamine 0.5mg/kg or tramadol 1mg/kg for pain control in 100 women undergoing uterine dilatation and curettage in turkey (24). in the results presented at the 35th annual european society of regional anaesthesia and pain therapy, they reported significantly better pain control in the group receiving ketamine. at the 30th annual european society of regional anaesthesia, a study from tunisia, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e68 presented by zghidi, reported the findings of comparison of ketamine and tramadol in controlling post laparotomy pain in 40 patients and revealed that ketamine was a more effective analgesic (26). these results are similar to another study by djaziri, presented at 32nd annual european society of regional anaesthesia and pain therapy (27). 3.4. need for rescue analgesic khajavi et al. used morphine as their rescue analgesic and showed that those receiving ketamine had significantly lower rescue morphine injections during the first 6 hours (0.47 ± 0.94 mg versus 2.50 ± 1.35 mg, p = 0.001) (29). burimsittichai and colleagues, on the other hand, did not see any significant difference between the groups regarding rescue morphine therapy (30). 3.5. side effect profile evaluation of included studies shows that ketamine has a safer side effect profile compared to tramadol. in the study by khajavi and colleagues, patients’ agitation was measured, using the ramsey scale score, 10 and 20 minutes after the injection of analgesics (29). the group receiving ketamine had significantly lower agitation compared to the group receiving tramadol. also, the prevalence of side effects was significantly lower in the ketamine group (20% for ketamine and 53% for tramadol). patients receiving tramadol experienced higher rates of nausea, vomiting, and hallucinations but the difference between the two groups was not statistically significant. in the study by burimsittichai et al. rates of nausea and vomiting were higher in the ketamine group, but the difference was not found to be significant compared to the either the tramadol group or the placebo group (30). the groups were found to have comparable rates of other side effects. in the study by yu c. the two groups were not significantly different regarding incidence of side effects (31). in a study by elkassem, effects of ketamine and tramadol were compared in patients undergoing cruciate ligament reconstruction surgery and it was found that tramadol had higher rates of side effects compared to ketamine (28). in the study by alp, ketamine was reported to have higher rates of side effects, which included increased heart rate and blood pressure (24). 4. discussion this systematic review aimed to explore existing literature to compare the analgesic effects of ketamine and tramadol in treating acute pain and compare their side effect profiles. results of this review show that low-dose ketamine is more effective than tramadol in pain control, while causing fewer side effects. three full text papers were included in this study alongside four studies only reported as abstract presentations in scientific gatherings. the authors concluded that these results demonstrate that use of ketamine for acute pain control is advisable. several systematic reviews have looked at analgesic effects of ketamine in the past. in 2018 karlow et al. looked at literature comparing low-dose ketamine to morphine for treatment of acute pain in the ed (32). this review included three studies and reached the conclusion that low-dose ketamine is equally effective as morphine in pain control, while having fewer significant side effects. they suggested using ketamine instead of morphine for treatment of severe pain in the ed (32). ghate and colleagues also looked at the effects of low-dose ketamine (0.15-0.3mg/kg) for pain control in the ed (33). they included 6 rcts and two observational studies. the authors concluded that ketamine is as effective as morphine in controlling pain and patients reported similar satisfaction rates. side effects reported for using ketamine included dysphoria, hallucinations, agitation, and confusion (33). a systematic review by lee and colleagues in 2016 included 6 studies and looked at the effectiveness of ketamine in patients with moderate to severe pain in the ed (34). they concluded that ketamine had comparable effects with morphine but it was found to be inferior to fentanyl in two studies. one of the included studies had found that ketamine was not superior to placebo at 0.15mg/kg and only showed analgesic effects at 0.3 mg/kg. the authors found that ketamine caused more neurologic (dizziness, headache, light-headedness, nystagmus, visual disturbance, drowsiness, numbness, or increased skeletal tone) and psychological (hallucination, dysphoria or confusion, agitation, disorientation, or mood change) side effects compared to morphine but had fewer cardiac side effects (major: hypoxia and hypotension; minor: tachycardia and hypertension) (34). other studies have also looked at ketamine in different settings. yousefifard et al. recently looked at the effects of ketamine in the prehospital setting and found that ketamine is less effective than morphine and fentanyl, but it also has fewer side effects (35). others have looked at ketamine in the perioperative setting. wang et al. looked at 20 clinical trials in cesarian sections (36), while riddell et al. looked at orthopedic surgeries (37), and garcia-henares jf. et al. looked at general surgery patients (38). all of these reviews found that ketamine is effective in reducing postoperative pain and decreasing the need for opioids without causing an increase in significant side effects. our results show that ketamine has consistently been shown to be superior to tramadol in pain control, also causing fewer significant side effects. therefore, we suggest the use of ketamine instead of tramadol as an opioid-spearing analgesic in treatment of acute pain. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. naghipour et al. 6 5. limitation we only found three articles that compared the analgesic effects of ketamine and tramadol, so we did not perform a meta-analysis. risk of bias for all three articles is shown in table 3. all three articles have low risk of bias regarding main and secondary outcomes. 6. conclusion the results of this review show that low-dose ketamine is more effective than tramadol in pain control, while causing fewer side effects. 7. declarations 7.1. acknowledgements none. 7.2. authors contributions all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. 7.3. funding support none. 7.4. conflict of 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[comparison of the suppressive effects of tramadol and low-dose ketamine on the patients with postoperative hyperalgesia after remifentanil-based anaesthesia]. hua xi kou qiang yi xue za zhi. 2005;23(5):404-6. 32. karlow n, schlaepfer ch, stoll crt, doering m, carpenter cr, colditz ga, et al. a systematic review and metaanalysis of ketamine as an alternative to opioids for acute pain in the emergency department. acad emerg med. 2018;25(10):1086-97. 33. ghate g, clark e, vaillancourt c. systematic review of the use of low-dose ketamine for analgesia in the emergency department. cjem. 2018;20(1):36-45. 34. lee en, lee jh. the effects of low-dose ketamine on acute pain in an emergency setting: a systematic review and meta-analysis. plos one. 2016;11(10):e0165461. 35. yousefifard m, askarian-amiri s, madani neishaboori a, sadeghi m, saberian p, baratloo a. pre-hospital pain management; a systematic review of proposed guidelines. arch acad emerg med. 2019;7(1):e55. 36. wang j, xu z, feng z, ma r, zhang x. impact of ketamine on pain management in cesarean section: a systematic review and meta-analysis. pain physician. 2020;23(2):135-48. 37. riddell jm, trummel jm, onakpoya ij. low-dose ketamine in painful orthopaedic surgery: a systematic review and meta-analysis. br j anaesth. 2019;123(3):32534. 38. garcia-henares jf, moral-munoz ja, salazar a, del pozo e. effects of ketamine on postoperative pain after remifentanil-based anesthesia for major and minor surgery in adults: a systematic review and meta-analysis. frontiers in pharmacology. 2018;9:921. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references march 23, 2020 total lab-confirmed cases: 23,049 total associated deaths: 1,812 total recovered cases: 8,376 new cases: 1,411 indicators of screened, infected and death cases screening (since march 4 till march 22, 2020; 5:30 pm gmt) value number of services delivered for covid-19 39,888,635 screened cases referred o the physician for their symptoms (%) 0.18 cases referred to the hospital by physician (%) 4.4 proportion of eligible cases followed-up for 50 new lab-confirmed cases (in last 72 h) age mean (standard deviation) 56 (18.5) age median (inter-quartile range) 56 (45-69) sex distribution (%) male 54 female 46 cases with at least one co-morbidity (%) 27.8 cases admitted in icu* (%) 13.6 cases with more severe forms of the disease ** 18.1 covid-19 deaths (in last 72 h) age mean (standard deviation) 70.1 (12.3) age median (inter-quartile range) 69 (65-80) cases over 60 years (%) 83.3 sex distribution (%) male 50 female 50 cases with at least one co-morbidity (%) 33.3 cases over 60 years or with at least one co-morbidity (%) 92 * to the total number of hospitalized covid-19 patients. ** based on available data, we considered patients with death outcome, as well as those admitted to icu or under mechanical ventilation as more severe cases. the information in this chart is based on hospitalized cases, and outpatients are not included in this calculation. inclusion of outpatients and asymptomatic cases would decrease the proportion of severe cases. geographic distribution of the number of suspected cases geographic distribution of the number of suspected cases admitted to the hospital geographic distribution of the number of lab-confirmed covid-19 cases geographic distribution of the number of lab-confirmed deaths numbers in the maps are per 100,000 populations source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1000 1500 19 -… 20 -… 21 -… 22 -… 23 -… 24 -… 25 -… 26 -… 27 -… 28 -… 29 -… 1… 2… 3… 4… 5… 6… 7… 8… 9… 10 -… 11 -… 12 -… 13 -… 14 -… 15 -… 16 -… 17 -… 18 -… 19 -… 20 -… 21 -… 22 -… 23 -… n um be r lab-confirmed and cured cases confirmed cases cured cases 0 50 100 150 200 19 -f eb 20 -f eb 21 -f eb 22 -f eb 23 -f eb 24 -f eb 25 -f eb 26 -f eb 27 -f eb 28 -f eb 29 -f eb 1m ar 2m ar 3m ar 4m ar 5m ar 6m ar 7m ar 8m ar 9m ar 10 -m ar 11 -m ar 12 -m ar 13 -m ar 14 -m ar 15 -m ar 16 -m ar 17 -m ar 18 -m ar 19 -m ar 20 -m ar 21 -m ar 22 -m ar 23 -m ar lab-confirmed deaths daily situation report on coronavirus disease (covid-19) in iran march 13, 2020 national committee on covid-19 epidemiology ministry of health and medical education, ir iran total lab-confirmed cases 11,364 total associated deaths 514 total recovered cases 3,529 new cases 1,289 confirmed cases m/f ratio: 1.4 age (year)  mean: 54  median: 55  minimum: 1  maximum: 98  more than 85% of cases were ≥ 42-year-old. associated deaths m/f ratio: 1.4 age (year)  mean: 67  median: 64  minimum: 3**  maximum: 91  more than 85% of cases were ≥ 44-year-old.  at least one comorbidity was reported in 43.7% of associated deaths. * given the prevalence of diabetes and cardiovascular disease the community is much higher than other underlying diseases, these conditions are also more prevalent among death. ** the only covid-19 death in under-10 children was observed in a 3-year old child who had leukemia. source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 200 400 600 800 1,000 1,200 1,400 1 9 -f e b 2 0 -f e b 2 1 -f e b 2 2 -f e b 2 3 -f e b 2 4 -f e b 2 5 -f e b 2 6 -f e b 2 7 -f e b 2 8 -f e b 2 9 -f e b 1 -m a r 2 -m a r 3 -m a r 4 -m a r 5 -m a r 6 -m a r 7 -m a r 8 -m a r 9 -m a r 1 0 -m a r 1 1 -m a r 1 2 -m a r 1 3 -m a r n u m b e r confirmed cases and associated deaths confirmed cases associated deaths -25 -15 -5 5 15 25 =<9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >= 80 percent age-sex distribution of confirmed cases male femal -30 -20 -10 0 10 20 30 =<9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >= 80 percent age-sex distribution of associated deaths male femal 54 54 50 38 22 3 0 10 20 30 40 50 60 fever cough po2<93 distress myalgia low gcs p e rc e n t early clinical symptoms of confirmed cases 16 16 3 3 2 2 1 1 0 0 10 0 5 10 15 20 p e rc e n t frequency of underlying diseases in associated deaths* archives of academic emergency medicine. 2019; 7 (1): e43 or i g i n a l re s e a rc h association of high serum adiponectin with the risk of malnutrition and worse outcome in head trauma patients; a cohort study mohammed ibrahim mohialdeen gubari1, mohammad javad hosseinzadeh-attar1,2, mostafa hosseini3, fadhil ahmed mohialdeen4, abdolreza norouzy1∗ 1. department of clinical nutrition, school of nutritional sciences and dietetic, tehran university of medical sciences, tehran, iran. 2. centre of research excellence in translating, nutritional science to good health, the university of adelaide, adelaide, australia. 3. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 4. community health department, technical college of health, sulaimani polytechnic university, sulaimani, iraq. received: june 2019; accepted: july 2019; published online: 24 august 2019 abstract: introduction: a number of studies have shown the association between serum adiponectin level and the nutritional status. this study aimed to evaluate the relation between serum adiponectin and changes in nutritional status of head trauma patients. methods: the current prospective cohort study was carried out on head trauma patients who were hospitalized in icu of a general teaching hospital, sulaimani, iraq. patients were divided into two groups based on their serum adiponectin level during the first 24 hours of admission (<15mg/l and ≥15 mg/l) and malnutrition and nutritional indices were compared between groups 1, 6 and 13 days after admission. results: sixty-four patients with the mean age of 35.97 ± 11.5 years were studied (59.4% male; 57% traffic accidents). the nutritional status of head trauma patients with serum adiponectin ≥15 mg/l significantly deteriorated from day 1 to 13 based on different nutritional status indices. bmi (p = 0.08), lbm (p = 0.002), apm (p = 0.009), and muac (p = 0.008) had a significant decreasing trend from day 1 to day 13 in patients with serum adiponectin level ≥ 15 mg/l. in addition, the number of high risk patients for developing malnutrition based on nutric score (p < 0.001) and the number of severely malnourished cases based on sga score (p < 0.001) significantly increased from day 1 to 13 in this group. the severity of disease based on apache (p < 0.001) and sofa (p < 0.001) scores increased in the mentioned cases during the follow up period. conclusion: serum adiponectin level ≥ 15 is associated with significant deterioration in nutritional status, increase in the risk of malnutrition, and worsening of the clinical outcome in patients with moderate to severe head trauma in icu. keywords: adiponectin; craniocerebral trauma; body composition; apache; organ dysfunction scores cite this article as: mohialdeen gubari m i, hosseinzadeh-attar m j, hosseini m, mohialdeen f a, norouzy a. association of high serum adiponectin with the risk of malnutrition and worse outcome in head trauma patients; a cohort study. arch acad emerg med. 2019; 7(1): e43. 1. introduction adiponectin is one of the bioactive proteins produced by white adipose tissue with a role in the energy homeostasis, lipid and glucose metabolism, and an anti-inflammatory activity (1). a high level of serum adiponectin is linked to cardiovascular diseases, metabolic disease, rheumatoid arthri∗corresponding author: abdolreza norouzy; department of clinical nutrition, school of nutritional sciences and dietetic, tehran university of medical sciences, tehran, iran. email: arnorouzy@sina.tums.ac.ir, tel: +985138002382 tis, and inflammatory bowel disease, whereas, a low level of serum adiponectin is linked to brain and myocardial infarctions (2, 3). a high concentration of adiponectin has been linked with increased rate of mortality in both cardiovascular diseases and stroke (4). increase in adiponectin has been observed not only in chronic diseases but also in patients with severe traumatic brain injury (5). the association between serum adiponectin and the nutritional status of haemodialysis patients is stated (6). the level of adiponectin also plays a role in pathogenesis of cachexia in heart failure (7). high level of adiponectin might lead to the loss of body weight in an attempt to normalize the metabolism of fatty acid. in anthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m e. mohialdeen gubari et al. 2 imal model, administration of adiponectin has been linked with increase in energy expenditure, causing weight loss (8). there is limited data on the association between circulatory adiponectin levels and nutritional status in head trauma patients. therefore, this study was conducted to investigate the relationship between serum adiponectin and changes in nutritional status of head trauma patients. 2. methods 2.1. study design and setting the current prospective cohort study was carried out on head trauma patients who were hospitalized in icu of a general teaching hospital of sulaimani located in the kurdistan region of iraq, from 20 november, 2017 to 07 august, 2018. patients were divided into two groups based on their serum adiponectin level in the first 24 hours of admission (<15mg/l and ≥15 mg/l) and malnutrition and nutritional indices were compared between groups 1, 6 and 13 days after admission to icu. this study was carried out according to the standard clinical ethics guideline, and its ethical approval was obtained from the ethics committee of tehran university of medical science (tums) with the code ir.tums.vcr.rec1396.2676. moreover, after the target patients and their families were provided with explanations about the study’s method and objectives, confidentiality of the data, and their freedom to quit the study, their written consent was obtained. 2.2. participants patients suffering from traumatic head injury, whose glasgow comma score (gcs) was less than 10 (moderate to severe head trauma), were included in the study. the exclusion criteria were age less than 18 and more than 65 years, history of anti-platelet medications, previous chronic diseases like liver diseases, malignancy, heart diseases, chronic obstructive air diseases, and hypertension, diabetes. 2.3. assessments in order to monitor the patients’ malnutrition status, the nutric score (nutrition assessment in critically ill) and sga score (subjective global assessment) were calculated within 24 hours from their admission, and then on the 6th and 13th days of their stay in icu. the patients’ nutritional status consisted of assessing their actual body weight through bed scale (balas digital body scale, tehran, iran), and body composition analysis (fat body mass (fbm) and lean body mass (lbm)) via bioelectrical impedance analysis (bia) (body stat’s, london) which was measured within 24 hours after their admission, and on the 6th and 13th days of their stay in the icu. moreover, a flexible measuring tape was used to measure their mid-upper arm circumference (muac) and a lange caliper (uk) was utilized in both hands of the patients in order to measure the thickness of adductor pollicis muscle (apm) within 24 hours after their admission, and on the 6th and 13th days of their stay in the icu. in order to measure the severity of the disease and incidence of organ dysfunction, sequential organ failure assessment (sofa) score and acute physiology and chronic health evaluation (apache ii) scoring systems were employed within 24 hours after admission, and on the 6th and 13th days of stay in the icu. 2.4. serum adiponectin measurement within 24 hours after admission in icu, 5 cc venous blood samples were collected from all patients, in the morning, in order to assess the concentration of serum adiponectin. afterwards, the blood samples were put on ice and centrifuged at 3000 ãůg, and the obtained sedimented plasma was frozen at -70 ◦c. after the blood samples were collected, immuneassay measurements were carried out in accordance with the manufacturer’s instruction by employing multiplexing technology as fully-automated evidence and semi-automated benchtop analyzer evidence investigator provided by shanghai korain biotech co. ltd. which specializes in antibodies, lab supplies of elisa kit, and protein for life science research. for this purpose, intra-assay was considered as cv<8% and inter-assay as cv<10%. 2.5. data gathering a check list consisting of patients’ age; gender; gcs; malnutrition status based on nutric and sga; nutritional status based on bmi, lmm, apm, fbm, and muac; serum adiponectin level; and severity of disease (apache ii and sofa) was collected for all patients on days 1, 6, and 13 after admission to icu. a phd student was responsible for data gathering. 2.6. statistical analysis data were analyzed using “spss version 22 for windows (spss inc. chicago, il, usa)”. mean ± standard deviation or number (%) was used to describe the characteristics of the participants. kolmogrov-smirnov test was used to examine the normal distribution of the continuous variables. chi-square test was used for comparison of categorical variables (nutric score, and sga score) between patients with serum adiponectin level of <15mg/l and ≥15 mg/l. independent samples t test was applied to compare the continuous data (bmi, fat body mass, lean body mass, apm, and mauac) between the two groups at 24hours after admission, day 6 and day 13 of staying in the icu. mann–whitney u test was applied to compare the non-parametric variables (apache, and sofa score) between the two groups. a two-sided p value of 0.05 was considered statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e43 3. results 3.1. baseline characteristics of studied patients sixty-four patients with the mean age of 35.97 ± 11.5 (20 – 64) years were studied (59.4% male; 57% traffic accidents). most of the patients (54 (84%)) had less/low risk of malnutrition on admission. the average bmi of the studied participants on admission was 28.01 ± 3.51 and their mauc, apm, fatty body mass, and lean body mass were 27.3 ± 3.2, 21.2 ± 3.8, 26.9 ± 6.35 and 48.2 ± 7.04, respectively. the patients’ average apache and sofa scores were 16.17 ± 5.07 and 11 ± 3.57, respectively. the mean serum adiponectin of patients was 21.9 ±11.8 (4.2 – 48. 4) mg/l (60.9% of cases ≥ 15 mg/l). 3.2. adiponectin and nutritional status table 1 compares the nutritional status indices between head trauma patients with serum adiponectin <15mg/l and ≥ 15 mg/l, at day1, 6, and 13 of admission to icu. the nutritional status of head trauma patients with serum adiponectin ≥15 mg/l significantly deteriorated from day 1 to 13 based on different nutritional status indices. bmi (p = 0.08), lbm (p = 0.002), apm (p = 0.009), and muac (p = 0.008) had significant decreasing trends from day 1 to day 13 in patients with serum adiponectin level ≥ 15 mg/l. in addition, the number of high risk patients for developing malnutrition based on nutric score (p < 0.001) and the number of severely malnourished cases based on sga score (p < 0.001) significantly increased from day 1 to 13 in this group. it should be noted that the severity of disease based on apache (p < 0.001) and sofa (p < 0.001) scores increased in the mentioned cases during the follow up period (table 2). 4. discussion based on the findings of the present study, serum adiponectin level ≥ 15 is associated with significant deterioration of nutritional status, increase in the risk of malnutrition, and worsening of the clinical outcome in patients with moderate to severe head trauma in icu. evidence on experimental studies demonstrated a consistent influence of adiponectin on inducing either weight loss or weight gain (8). the presence of a clear cause and effect relationship between reducing the weight and increase in the concentration of serum adiponectin has not been confirmed in humans. in pre-dialysis chronic kidney disease patients, high serum adiponectin was independently related to protein energy wasting and decrease in muscle mass (9). high level of adiponectin was associated with worse nutritional status of patients with renal disease and suggested to contribute to the pathogenesis of undernutrition in such patients (10). high adiponectin level has also been suggested to have a role in the pathogenesis of cachexia in heart failure (7). in metabolic disorders (anorexia and obesity) the level of adiponectin is inversely associated with bmi and fat mass (11). however, the increased concentration of adiponectin in anorexia nervosa was found to be less than what we reported in our head trauma patients. adiponectin concentration was found to be decreased in obese individuals who tried to reduce their weight by dieting or gastric surgery (12). however, the concentration of plasma adiponectin had not decreased in non-obese healthy people who tried to lose weight (13). plasma adiponectin level was also found to be related to worsening of the patients’ outcome. high serum adiponectin level is associated with increased 1-week mortality in those with intra-cerebral haemorrhagic disease (14). in acute respiratory illnesses the high level of serum adiponectin was found to correlate with the severity of the illness and increased mortality of the patients (15). in patients with coronary artery disease, high level of adiponectin was found to be related with an increase in adverse cardiovascular outcomes (16). in traumatic brain injury, high level of adiponectin was found to be independently associated with the worse clinical outcome and severity of the disease in traumatic brain injury (5). in agreement with other studies, we found that high level of adiponectin significantly correlated with severity of the disease and the clinical outcome. apache score, which reflects the severity of trauma was found to be high in patients who had higher levels of adiponectin. in addition, sofa score, which reflects organ dysfunction, was also found to be significantly high in patients with adiponectin ≥ 15 mg/l. some inflammatory mediators have been implicated to be linked to severity and clinical outcomes of traumatic brain injury. these inflammatory mediated cytokines are found to increase after traumatic head injury (17, 18). the antiinflammatory effect of adiponectin is exerted by blocking the pro-atherogenic process in endothelial cells and releasing ampactivated kinase, increasing sensitivity to insulin and reducing the risk of glucose tolerance (19). adiponectin has been shown to exert anti-inflammatory and cerebral protective effects. clear evidence has shown the inverse relationship between several inflammatory markers and plasma adiponectin. adiponectin has been shown to modulate signalling pathways in certain types of cells (20). impairment and dysfunction of the organ is a result of inflammatory reaction process during ischemia reperfusion injury (21, 22). nitric oxide and ampk are two molecules of cellular signal transduction, which are considered to be involved in adiponectin’s cardio-protecting activities (23). therefore, the main part of adiponectin’s beneficial effect on cerebrovascular injury is its anti-inflammatory effect, ameliorating and reducing the production of apo, il-8, il1b, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m e. mohialdeen gubari et al. 4 table 1: comparing the nutritional status indices between groups at different days of admission to intensive care unit nutritional index serum adiponectin level (mg/l) p-value <15 (n = 25) ≥15 (n = 39) body mass index (bmi) day 1 28.17 ± 4.05 27.90 ± 3.16 0.77 day 6 28.02 ± 4.18 26.96 ± 2.9 0.24 day 13 28.01 ± 4.15 26.46 ± 2.89 0.08 fat body mass (fbm) day 1 25.0 ± 5.09 28.15 ± 6.35 0.05 day 6 24.6 ± 5.9 26.74 ± 5.9 0.16 day 13 24.56 ± 5.8 25.46 ± 5.8 0.55 lean body mass (lbm) day 1 50.64 ± 7.03 46.73 ± 6.69 0.02 day 6 50.19 ± 6.95 45.17 ± 6.58 0.005 day 13 49.71 ± 6.52 44.51 ± 6.36 0.002 abductor pollicis muscle (apm) day 1 21.79 ± 4.56 20.96 ± 3.41 0.40 day 6 21.80 ± 4.56 19.76 ± 2.85 0.03 day 13 21.82 ± 4.35 19.33 ± 3.04 0.009 mid upper arm circumference (muac) day 1 27.02 ± 4.1 27.5 ± 2.4 0.56 day 6 27.51 ± 3.4 26.57 ± 2.67 0.22 day 13 27.71 ± 3.39 25.68 ± 2.53 0.008 nutric score (high risk for malnutrition) day 1 7 (28.0) 5 (12.8) 0.12 day 6 2 (8.0) 31 (79.5) <0.001 day 13 1 (4.0) 32 (82.1) <0.001 sga score (severely malnourished) day 1 0 (0.0) 0 (0.0) 0.13 day 6 0 (0.0) 6 (15.4) <0.001 day 13 0 (20.0) 28 (71.8) <0.001 data are presented as mean ± standard deviation or number (%). table 2: comparing the severity of disease between groups at different days of admission to intensive care unit severity of disease serum adiponectin level (mg/l) p-value <15 (n = 25) ≥15 (n = 39) apache ii score ) day 1 12 (4) 19 (6) 0.006 day 6 12 (4) 12 (5) <0.001 day 13 14 (4) 23 (6) <0.001 sofa score day 1 8 (4) 22 (7) <0.001 day 6 8 (4) 14 (5) <0.001 day 13 10 (3) 16 (4) <0.001 data are presented as median (iqr). sofa: sequential organ failure assessment (sofa) score; apache ii: acute physiology and chronic health evaluation. and tnf (24). it seems that serum adiponectin level could be considered as a good screening tool for detection of patients at risk for developing malnutrition and poor outcome following head trauma. therefore, finding high risk patients and ameliorating their nutritional status may be a useful strategy to improve the outcome of patients with moderate to severe trauma who are admitted to icu. we recommend a large study to show/investigate the cause and effect relationship between adiponectin and nutritional status in head trauma this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e43 patients. the inclusion of both male and female patients with 13 days followup, the application of various methods to assess the nutritional status, and anthropometric measurement are among the strengths of this study. in addition, the actual weight of the patients was assessed using bed scale for the first time in iraq. 5. limitations one of the limitations of the current study was measuring serum adiponectin once, on admission. measuring serum adiponectin at different stages and times could provide better understanding of the behaviour of this adipocytokine. another limitation was the small sample size of the current study, investigating the association of serum adiponectin with nutritional status in a large sample size might have more accurate results. 6. conclusion based on the findings of the present study, serum adiponectin level ≥ 15 is associated with significant deterioration in nutritional status, increase in the risk of malnutrition, and worsening of the clinical outcome in patients with moderate to severe head trauma in icu. 7. appendix 7.1. acknowledgements we would like to acknowledge dr. haval othman (sbai, desa, mbchb) and mr. khalid anwar hama-ghareeb (bsc, msc) for their assistance in data collection. in addition, special thanks to all the staffs at sulaimani teaching hospital, for their assistance for performing this project. 7.2. author contribution mohammed gubari has made substantial contribution to the conception, design of the work, data collection, data analysis, data interpretation, and revising the manuscript. dr. hosseinzadeh: has made substantial contributions to the conception, design of the work and interpretation of the data and revising the manuscript. dr. norouzy: has made substantial contributions to the conception, design of the work and interpretation of the data and revising the manuscript. dr. mohialdeen: contributed to data collection, and revising the manuscript. dr. hosseini: was the statistical advisor and made contribution in the data analysis and interpretation of the results. authors orcids mohammed ibrahim mohialdeen gubari: 0000-0002-28733981 mohammad javad hosseinzadeh-attar: 0000-0002-57874089 mostafa hosseini: 0000-0002-1334-246x 7.3. funding/support self-funding, part of phd project. 7.4. conflict of interest the authors declare that they have no competing interests. 7.5. availability of data and material: all data are available on request. references 1. ahima rs, osei sy. 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m, ayatollahi m, hassanzadeh j, geramizadeh b, et al. adiponectin as a novel indicator of malnutrition and inflammation in hemodialysis patients. iranian journal of kidney diseases. 2013;7(4). 7. mcentegart mb, awede b, petrie mc, sattar n, dunn fg, macfarlane ng, et al. increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and b-type natriuretic peptide. european heart journal. 2007;28(7):829-35. 8. fruebis j, tsao t-s, javorschi s, ebbets-reed d, erickson mrs, yen ft, et al. proteolytic cleavage product of 30-kda adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. proceedings of the national academy of sciences. 2001;98(4):2005-10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m e. mohialdeen gubari et al. 6 9. hyun 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et al. plasma adiponectin as an independent predictor of early death after acute intracerebral hemorrhage. clinica chimica acta. 2011;412(17-18):1626-31. 15. walkey aj, rice tw, konter j, ouchi n, shibata r, walsh k, et al. plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. critical care medicine. 2010;38(12):2329. 16. schnabel r, messow cm, lubos e, espinola-klein c, rupprecht hj, bickel c, et al. association of adiponectin with adverse outcome in coronary artery disease patients: results from the athero gene study. european heart journal. 2008;29(5):649-57. 17. finfer sr, cohen j. severe traumatic brain injury. resuscitation. 2001;48(1):77-90. 18. mussack t, biberthaler p, kanz k-g, wiedemann e, gippner-steppert c, mutschler w, et al. serum s-100b and interleukin-8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury. critical care medicine. 2002;30(12):2669-74. 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this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion appendix references emergency. 2018; 6 (1): e43 or i g i n a l re s e a rc h intravenous haloperidol versus midazolam in management of conversion disorder; a randomized clinical trial mohammadali jafari1, amir aliheidari biuki1∗, majid hajimaghsoudi2, mehdi bagherabadi1, ehsan zarepur3 1. emergency medicine department, shahid sadoughi hospital, school of medicine, shahid sadoughi university of medical sciences, yazd, iran. 2. emergency medicine department, shahid sadoughi hospital, trauma research center, shahid sadoughi university of medical sciences, yazd, iran. 3. isfahan cardiovascular research center, cardiovascular research institute, isfahan university of medical sciences, isfahan, iran. received: april 2018; accepted: july 2018; published online: 14 july 2018 abstract: introduction: conversion disorder is a condition in which the patient shows psychological stress in physical ways. this study aimed to compare the effects of haloperidol versus midazolam in patients with conversion disorder. methods: this double-blind randomized clinical trial was conducted on patients with conversion disorder who had presented to the emergency department, throughout 2015. patients were randomly divided into two groups and were either treated with 2.5 mg of intravenous (iv ) haloperidol or 2.5 mg of iv midazolam. recovery rate, time to recovery, and side effects of both drugs 1 hour, 24 hours, and 1 week after treatment were compared using spss19. results: 140 patients were divided into two groups of 70. there were no significant differences between the groups regarding the baseline characteristics. 12 (17.1%) patients who were treated with iv haloperidol experienced drug side effects within 1 hour and 12 (17.1%) within 24 hours, while only 3 (4.3%) patients in iv midazolam experienced side-effects within 1 hour after drug administration (p = 0.026). the symptoms of the disease subsided in 45 (success rate: 64.3%) patients in midazolam and in 64 (success rate: 91.5%) participants in haloperidol group (p<0.001). mean recovery time was 31.24 ± 7.03 minutes in iv midazolam and 30.53 ± 7.11 minutes in iv haloperidol group (p = 0.592). absolute risk reduction (arr) of treating patients with haloperidol compared to midazolam is about 27%. conclusion: the response of patients to treatment with haloperidol is clearly better than midazolam. although more transient and minor side-effects were observed in the group treated with haloperidol compared to midazolam group, serious side-effects were rare for both treatments. keywords: conversion disorder; hysteria; haloperidol; midazolam; side effects; intravenous © copyright (2018) shahid beheshti university of medical sciences cite this article as: jafari m, aliheidari biuki a, hajimaghsoudi m, bagherabadi m, zarepur e. intravenous haloperidol versus midazolam in management of conversion disorder; a randomized clinical trial. emergency. 2018; 6(1): e43. 1. introduction a large number of patients with physical manifestations of underlying psychological disorders present to the emergency department annually (1). conversion disorder (cd) or hysteria is a diagnostic category defined in some psychiatric classification systems under the main branch of somatoform disorders. this disorder is more prominent in women, early adulthood, and uneducated pa∗corresponding author: amir aliheidari biuki; emergency medicine department, shahid sadoughi hospital, ibn sina st., riazi sq., po box 8915887857, yazd, iran. tel/fax: 0098 353 8224000 e-mail: amir6381@gmail.com tients. the symptoms may be established unconsciously and involuntarily (2). this illness is more frequent in histrionic personalities. clinical signs of the disease include a wide range of different organs being involved: movement disorders including paralysis, ataxia, and aphonia, sensory disorders including blindness, anosmia and stocking-glove paresthesia, and consciousness disorders including coma and pseudo-seizure (3-6). based on studies in non-emergent cases, the best management for long-term treatment is behavioral therapy accompanied by treating other underling psychological impairments (4-6). however, the management of patient’s signs and symptoms in the emergency department is quite necessary because it helps the patients and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. jafari et al. 2 their families to overcome one of the most stressful situations they have ever been faced with. so, administration of the required drugs is essential to alleviate the symptoms as soon as possible. since years ago, administration of haloperidol and some types of benzodiazepines like lorazepam and diazepam as well as lithium and sodium valproate was a common practice in management of psychiatric emergencies, particularly in conversion disorders, and their efficacies have been approved so far (7, 8). considering the high frequency of patients with psychological or neurological problems, especially conversion disorders, admitted to emergency departments and the urgent need to reduce the severity of symptoms in order to tranquilize tremulous patients and their relatives, and since haloperidol has more side-effects than midazolam, which has a rapid effect and is available in most cases (2, 6, 7), we decided to evaluate and compare the effects of intravenous (iv ) haloperidol and midazolam in patients with conversion disorders presenting to emergency departments. 2. methods: 2.1. study design and setting this double-blind parallel randomized clinical trial was conducted on 140 patients with conversion disorder (based on dsm-iv, diagnostic and statistical manual of mental disorders, 4th edition) who had presented to emergency department of shahid sadoughi hospital, yazd, central iran, in 2015. the protocol of this research project was approved by the ethics committee of shahid sadoughi university of medical sciences and registered on iranian registry of clinical trial (trial registration number: irct 2015100712050n2). we did not perform any additional invasive procedures and patient’s written consent was taken. the purpose of the study was explained to the patients. a written consent form was obtained from all patients and patients’ information remained confidential. patients were informed of the probable drug side-effects and recommended to come back in case of the mentioned complications happening. ethical issues related to human studies (according to the helsinki statement) were considered. 2.2. participants all patients aged 18 to 60 years who met the following inclusion criteria were enrolled in the study: any alteration or impairment in daily performances, an experience of recent emotional stress, a symptom or deficit that could not be explained by another medical or mental disorder, and a symptom or deficit that was not restricted to pain or sexual disorders. the exclusion criteria were as follows: patients with abnormal vital signs, pregnant or lactating women, addicted patients, patients with known hepatic or renal failure, severe cardio-pulmonary impairment, cases of parkinsonism, a history of recent seizure or patients who were taking antiepileptic agents, long q-t syndrome, having allergies to neuroleptics or benzodiazepines, a history of psychiatric disorders, and patients who did not sign the informed written consent. 2.3. procedures after patients’ admission to the emergency department, conversion disorder diagnosis was made by an emergency medicine specialist, based on dsm-iv, diagnostic and statistical manual of mental disorders, 4th edition. after evaluating eligibility criteria, history taking and physical examination were done by an emergency medicine resident and the data were recorded. the participating patients were randomly assigned to the two groups based on the table of random numbers by an independent physician blind to the study (random sequence number generation was done by a computer). 2.5 mg of iv haloperidol (halodic, 5 mg/1ml, exir pharmaceutical co.) was administered to the patients in group a and 2.5 mg of iv midazolam (midazolam aburaihan, 5 mg/1ml, aburaihan pharmaceutical co.) was prescribed for patients in group b (based on reliable guidelines). the drugs were administered to the patients by a trained nurse, and the assessor was blind. after drug administration, all patients remained under direct supervision of an emergency medicine resident with concurrent cardiac monitoring (heart rate, o2 saturation, diastolic blood pressure, systolic blood pressure). the patients were followed up through the next 24 h and 1 week after treatment. the outcomes were recorded. all patients and emergency staff including physicians, nurses, and researchers were blind to the therapeutic groups. 2.4. data gathering a questionnaire was completed for all the patients including demographic data, marital status, level of education, recent emotional stress, taking medications, underlying physical illness, movement disorders, sensory disorders, consciousness disorders, recovery rate, time of recovery, and side-effects in both groups. a trained emergency medicine resident was responsible for data gathering. 2.5. outcome recovery rate (acute symptoms subsiding), time to recovery, and side-effects of haloperidol (extrapyramidal and anticholinergic side-effects, and hypotension) and midazolam (decreased respiratory rate, apnea, drowsiness, nausea, vomiting) at 1 hour, 24 hours, and 1 week after treatment were considered as main study outcomes and compared between the groups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e43 figure 1: follow-up of candidates for receiving intravenous haloperidol or midazolam (according to consort statement). 2.6. statistical analysis the participants were selected via convenience sampling method. the sample size was determined to be at least 52 patients in each group and it was achieved by 95% confidence coefficient (α=0.05) and power of 80% (β=0.2); however, 70 subjects were included in each group. the data were analyzed by an experienced statistics consultant. all the collected data were imported to spss19 (ibm, spss statics for windows, armonk, ibm corp.) and analyzed using statistical tests. mean and standard deviation (sd) for quantitative variables and frequencies (percentages) for qualitative variables were calculated. to compare the quantitative variables between two groups, independent student’s t-test (or mannwhitney test) was used and categorical variables were compared between the two groups using the chi-square test. p < 0.05 was considered as statistically significant. 3. results 3.1. baseline characteristics 140 patients with conversion disorder manifestations were enrolled (figure 1). patients were randomly divided into two groups of 70: group a who were treated with haloperidol, and group b who received midazolam. the mean age of patients in midazolam and haloperidol groups was 29.67± 7.50 and 29.54 ± 7.22 years, respectively (p = 0.918). table 1 compares the baseline characteristics of studied patients between the groups. there were no significant differences between the groups regarding the means of educational level (p = 0.988), marital status (p = 1.00) and sex (p = 0.365). 3.2. outcomes 12 (17.1%) patients who were treated with iv haloperidol experienced drug side-effects within 1 hour and 12 (17.1%) within 24 hours, while only 3 (4.3%) patients in iv midazolam this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. jafari et al. 4 table 1: comparing baseline characteristics of patients with conversion disorder treated with iv midazolam (n = 70) and iv haloperidol (n = 70) variable midazolam haloperidol p age (year) mean ± sd 29.67 ± 7.50 29.54 ±7.22 0.918 sex male 29 (41.4) 26 (37.1) 0.365 female 41 (58.6) 44 (62.9) marital status single 23 (32.9) 24 (43.3) 1.000 married 47 (67.1) 46 (65.7) level of education uneducated 4 (5.7) 4 (5.7) junior school 30 (42.9) 28 (40.0) 0.998 high school 23 (32.9) 24 (43.3) bachelor and higher 13 (18.6) 14 (20.0) recent emotional stress yes no 70 (100.0) 70 (100.0) taking medications yes no 70 (100.0) 70 (100.0) underlying physical illness yes no 70 (100.0) 70 (100.0) movement disorders no 44 (62.9) 43 (61.4) paralysis 16 (22.9) 15 (21.4) 0.893 aphonic 10 (14.3) 12 (17.1) sensory disorders no 54 (77.1) 53 (75.7) 1.000 stocking-glove 16 (22.9) 17 (24.3) consciousness disorders no 42 (60) 44 (62.9) coma 13 (18.6) 14 (20) 0.812 seizure 15 (21.4) 12 (17.1) vital signs heart rate 79.59 ± 4.14 79.60 ± 3.99 0.983 o2 saturation 95.39 ±1.19 95.41 ± 1.25 0.891 dbp 76.43 ± 7.80 76.57 ± 7.64 0.913 sbp 117.86 ± 8.14 118.43 ± 8.45 0.684 data were presented as mean ± standard deviation or frequency (%). dbp: diastolic blood pressure, sbp: systolic blood pressure. experienced side-effects within 1 hour after drug administration (p = 0.026). the symptoms of the disease subsided in 45 (success rate: 64.3%) patients in midazolam and 64 (success rate: 91.5%) patients in haloperidol group (p<0.001). mean recovery time was 31.24 ± 7.03 minutes in iv midazolam and 30.53 ± 7.11 minutes in iv haloperidol group (p = 0.592). absolute risk reduction (arr) of treating patients with haloperidol compared to midazolam is about 27%. 4. discussion the results of this clinical trial showed that the success rate of iv haloperidol in managing conversion disorder is significantly higher than midazolam (91.5% versus 64.3%). however, patients who were treated with iv haloperidol experienced more transient and minor side-effects 1 hour, 24 hours, and 1 week after treatment. serious side-effects for both treatments were rare. in a study conducted by esmailian et al. (2015) the efficacy and safety of haloperidol and midazolam have been evaluated in management of 48 patients with manifestations of conversion disorder, who were admitted to the emergency department. the efficacy of both drugs in alleviating the symptoms of the disease was reported to be the same (9). in another study conducted by nobay et al. (2003), the effects of 3 medications including midazolam, haloperidol, and lorazepam were evaluated in patients with behavioral disorthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e43 ders. the results showed that the efficacy of all 3 drugs was the same (10). the effects of haloperidol plus promethazine vs midazolam were investigated in sedation of agitated patients presenting to the psychiatric emergency room in another study. their study showed that both treatments were effective (11). the difference between the results of this study and previous studies almost all of which indicate that midazolam is more effective on psychological stresses, may be attributed to the design and the drugs used. in addition, our study was held in the emergency department of a large teaching hospital in south and south east of iran with a high frequency of new patient admission. this means that the researchers of the study were often under excessive pressure and that they may have been at the risk of over-assessment (12). despite the complications of haloperidol, it is currently still the drug of choice in emergency situations (13). in the mid-1980s, several studies looked at the effect of haloperidol in treatment of devastating diseases (10, 14). in this study, we observed that haloperidol is effective in 91.5% of cases. however, midazolam was only effective in 64.3% of patients. in another study, similar results have been reported in 81 patients. in addition, further research is required to discover drugs with faster and better effect to use in combination with other drugs (15). the present study investigated the clinical effects of midazolam and haloperidol in patients with conversion disorder at 1 h, 24 h and one week after administration. in the two intervals of 1 and 24 h after initiation of treatment, the sideeffects of haloperidol were significantly higher than midazolam. contrary to the results of the present study, huf et al. (2003) reported that side-effects of haloperidol plus promethazine are not significantly more than midazolam in patients with conversion disorder (11). in another study, powney et al. (2012) reported the results of 32 previous studies that measured the effects of haloperidol compared to other therapies. according to the study, two clinical trials have reported that patients in the haloperidol group had experienced one or more adverse events compared to the placebo group (n=395, rr=1.64, ci 1.2323-2.20) (16). according to the results of the present trial as well as previous studies, it is clear that the probable side-effects of both drugs are mostly seen within the first few minutes after administration. in the study by huf et al. (2003), it is reported that both cases of severe side-effects occurred in the first 20 min after injection of haloperidol and midazolam and they have been associated with other factors. so, preparing for probable side-effects in the first few minutes after injection as well as considering the patient’s clinical records such as a history of epilepsy or drug consumption are necessary (11). it suggested that future studies investigate the sedation speed, type and severity of side-effects, and optimal dose of haloperidol and midazolam, and the effect of combination therapy with haloperidol and midazolam in patients with conversion disorder. in addition, to assess the possible influence of stressful situations in emergency department, doing further studies in other wards of the hospital with calmer conditions is recommended. 5. limitation sedation speed and severity of side-effects were not investigated in this single-center study. the main limitation of the present study was that we did not consider a group treated by combination therapy with haloperidol and midazolam. 6. conclusion based on the results, the response of patients to treatment with haloperidol is clearly better than midazolam. although transient and minor side-effects in the group treated with haloperidol were more than midazolam, serious side-effects were rare for both treatments. 7. appendix 7.1. acknowledgements we would like to thank the patients for their cooperation and their families for assistance. also, we would like to thank the staff of shahid sadoughi hospital, yazd, iran. we also thank the hospital staff and authorities for their support. 7.2. author’s contribution all the authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 7.3. funding/support this study enjoyed the support of the staff of shahid sadoughi teaching hospital affiliated to shahid sadoughi university of medical sciences. we used the equipment and facilities of this hospital. dr. aliheidari provided the financial support. 7.4. conflict of interest all authors declare that they have no conflicts of interest. references 1. american psychiatric association. diagnostic and statistical manual of mental disorders, fifth edition. washington, dc: american psychiatric association. 2013. 2. spiegel d, lewis-fernandez r, lanius r, vermetten e, simeon d, friedman m. dissociative disorders in dsm5. annu rev clin psychol. 2013;9:299-326. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. jafari et al. 6 3. hi k, bj s. synopsis of psychiatry. new york: williams & wilkins. 1998;8th ed:634-39. 4. stone j, lafrance wc, jr., brown r, spiegel d, levenson jl, sharpe m. conversion disorder: current problems and potential solutions for dsm-5. j psychosom res. 2011;71(6):369-76. 5. bidaki r, zarepur e, akrami m, mohammad m. functional 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midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. acad emerg med. 2004;11(7):744-9. 11. trec collaborative group. rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. bmj. 2003;327(7417):708-13. 12. baldacara l, sanches m, cordeiro dc, jackoswski ap. rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. rev bras psiquiatr. 2011;33(1):30-9. 13. cascella m. anesthesia awareness. can midazolam attenuate or prevent memory consolidation on intraoperative awakening during general anesthesia without increasing the risk of postoperative delirium? korean j anesthesiol. 2015;68(2):200-2. 14. clinton je, sterner s, stelmachers z, ruiz e. haloperidol for sedation of disruptive emergency patients. ann emerg med. 1987;16(3):319-22. 15. griffin ce, 3rd, kaye am, bueno fr, kaye ad. benzodiazepine pharmacology and central nervous systemmediated effects. ochsner j. 2013;13(2):214-23. 16. powney mj, adams ce, jones h. haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). cochrane database syst rev. 2012;11:cd009377. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods: results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e41 or i g i n a l re s e a rc h job burnout, stress, and satisfaction among emergency nursing staff after health system transformation plan in iran nader tavakoli1, seyed hosein shaker1, siamak soltani2, mohsen abbasi1, milad amini3, ali tahmasebi3, seyed mohammad hosseini kasnavieh1∗ 1. department of emergency medicine, iran university of medical sciences, tehran, iran. 2. department of forensic medicine, iran university of medical sciences, tehran, iran. 3. trauma and injury research center, iran university of medical sciences, tehran, iran. received: may 2018; accepted: july 2018; published online: 13 july 2018 abstract: introduction: job burnout, stress, and satisfaction are linked to quality of care, patient outcomes and retention of staff. this study was conducted to determine the mentioned issues among emergency nurses. methods: this cross-sectional study was conducted on all nurses working in the emergency departments of 10 hospitals in tehran, iran, in 2017. standard questionnaires were used for gathering the data of participants regarding job burnout, stress, and satisfaction. results: 709 (90%) participants returned the completed questionnaires (58.9% female). the mean age of the nurses was 33 (sd = 7) years. the level of job burnout was moderate in 76.1%, low in 22.5%, and high in 1.4% of the nurses. the level of burnout in the married nursing staff was lower than single nurses (3.78 ± 0.98 versus 4.14 ± 0.58, p = 0.049). the level of job satisfaction was moderate in 61.1%, low in 22.2%, and high in 16.7%. there was a significant correlation between age and job satisfaction (p = 0.027, r = 0.3). job burnout was directly correlated with job stress (p ≤0.001, r = 0.57) and job burnout was negatively correlated with job satisfaction (p = 0.001, r = -0.41). conclusion: more than 60% of the studied emergency nurses had moderate levels of job burnout, stress, and satisfaction. job burnout had a direct correlation with job stress and indirect correlation with job satisfaction. planning to reduce burnout of the emergency nursing staff seems to be necessary. keywords: burnout, professional; occupational stress; job satisfaction; nurses; emergency responders; hospitals © copyright (2018) shahid beheshti university of medical sciences cite this article as: tavakoli n, shaker seyed h, soltani s, abbasi m, amini m, tahmasebi a, kasnavieh seyed m. job burnout, stress, and satisfaction among emergency nursing staff after health system transformation plan in iran. emergency. 2018; 6(1): e41. 1. introduction e mergency nursing staff deal with life and death situations every day and they have to provide skilled, quality care for patients (1). high patient loads, long shifts, demanding physicians, a fast-paced environment, and working in an environment with emotional and physical challenges can cause problems for nurses in the emergency department (2). one critical problem in the modern working environments is job burnout, which has become preva∗corresponding author: seyed mohammad hosseini kasnavieh. rasoul akram hospital, niaiesh st, satarkhan st, tehran, iran. email: hosseinikasnavieh.sm@iums.ac.ir phone number: 00982166539233 lent dramatically over the past decade (3, 4). although job burnout may occur in any job, it can be more common in jobs that are related to helping people (such as health department staff ) (5-7) and among health department staff, nurses are more at risk of job burnout than others (8). the effects and consequences of burnout can be examined from three aspects including the nurse, client (patient), and organization (9). the cost of nursing turnover (due to burnout) can reach as high as 150% of an employee’s annual compensation. this can cause a decrease in safety of patients (10), raising the patient’s negative attitude towards the nursing staff (11), and decreasing the quality of healthcare (12). patient satisfaction can also be related to job burnout among the hospital staff and thus, should be considered. higher levels of job satisfaction among nurses have been positively this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. tavakoli et al. 2 linked to improved quality of care, patient outcomes (13) and retention of staff (14). job stress is also serious among helping professions (15). some of the stressors in the emergency department include aggression and violence at work (16), work overload (17) and others. given that national projects such as the health system reform plan are being implemented in iran (the plan has increased the workload among nurses) and since there is a shortage of nursing staff in iran, addressing these issues appears to be of great importance. this study was conducted to determine the status of job burnout, stress, and satisfaction and their relationship. 2. methods 2.1. study design and setting this prospective cross-sectional study was conducted in march 2017 in ten public educational hospitals of tehran, iran. the ten hospitals were general public hospitals affiliated to iran university of medical sciences and were among the most important hospitals in affiliation with this university. the necessary permissions were obtained from the medical ethics committee (ir.iums.rec 1394. 27240). moreover, the subjects were assured of the right to withdraw from participation at any time and confidentiality of their responses. 2.2. participants using census sampling, all nursing staff members working in the emergency departments of the above-mentioned hospitals were included for being evaluated regarding the purposes of this study. a total of 788 nurses were employed in the emergency departments of the ten hospitals. 2.3. data gathering four questionnaires were used in this study. at the beginning of the first questionnaire, the objectives of the study were generally explained to the respondents. in the first questionnaire, demographic information of the nurses such as age, sex, marital status, education level, employment type and work experience was questioned. an assessment of burnout was made using the maslach burnout inventory (mbi)(18). mbi is the most widely used measure of burnout, which consists of 22 questions relating to the three components of burnout; emotional exhaustion, depersonalization and personal accomplishment. all items were scored on a seven-point rating scale (1= never, 7 = every day). higher scores indicate higher levels of burnout. previous research using mbi among nurses suggests that it is highly reliable (e.g., laschinger& leiter, 2006, reported cronbach’s îś level of 0.91 for emotional exhaustion and 0.80 for depersonalization) (19). the hospital stress scale (hss-35) was used to measure job stress. the scale consisted of 35 items, which were scored based on a 5-point likert scale, allocated points were: never (score 1), rarely (score 2), sometimes (score 3), mostly (score 4) and always (score 5). the mean scores represented the measured stress levels, which ranged from 1 to 5, with 1 being desirable (insignificant stress) and 5 being undesirable (severe stress). the reliability and validity of the scale developed by badiqi et al. have been confirmed and the scale has been frequently used in numerous studies in iran (20, 21). the job descriptive index ( jdi) scales was used for measurement of job satisfaction (22). the jdi measures five areas of a job to assess satisfaction: type of work, payment, promotion opportunities, supervision, and co-workers. the jdi has been the target of numerous validation and reliability studies. all of the scales are reported to have corrected split-half internal consistency coefficients exceeding 0.80, and average test-retest reliabilities of 0.57 (23). an individual acted as an interviewer in this study, who received preliminary trainings. 2.4. statistical analysis the data of the questionnaires were coded and then analyzed via spss software version 21 in two levels of descriptive and analytical statistics. in descriptive statistics, parameters such as frequency, frequency percentage, and standard deviation were used. to conduct analytical tests, tests such as the independent samples test as well as one-way anova were used, whereas the pearson correlation coefficient was used to examine the relationship between the three variables including job burnout, stress, and satisfaction. the significance level in all the analytical tests was 0.05. 3. results 3.1. baseline characteristics of studied nurses 788 nursing staff members working in the emergency department of the 10 surveyed hospitals were questioned. 709 (90%) participants returned the completed questionnaires (58.9% female, 65.3% married). the mean age of the nurses was 33 (sd = 7) years and 57.4% were in the range of 23-32 years. with regard to work experience, 48.4% of the nurses had 1-7 years of experience with the mean work experience of 9 (sd = 7) years. most of the nursing staff members (55.7%) had undergraduate education. other demographic characteristics are presented in table 1. 3.2. job burnout the level of job burnout was moderate in 76.1%, low in 22.5%, and high in 1.4% of the nurses. the only demographic varithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e41 table 1: baseline characteristics of the studied nurses variables number (%) sex female 418 (58.9) male 291 (41.1) age (year) 23-32years 406 (57.4) 33-42years 230 (32.4) 43-54 years 73 (10.3) marital status single 246 (34.7) married 463 (65.3) educational level diploma 142 (20) associate degree 142 (20) bachelor’s degree 395 (55.7) master’s degree 21 (2.9) phd 10 (1.4) employment status permanent 172 (24.2) fixed-term 57 (8.1) contractual 412 (58.1) casual 46 (6.5) corporate 23 (3.2) work experience (year) 1-7 343 (48.4) 8-14 211 (29.7) 15-21 100 (14.1) 22-28 55 (7.8) able related to job burnout was the marital status (table 2). the level of burnout in the married nursing staff was lower than single nurses (3.78 ± 0.98 versus 4.14 ± 0.58, p = 0.049). 3.3. job stress the level of job stress was moderate in 80.3%, low in 10.5%, and high in 9.2% of the nurses. the relationship between job stress and demographic characteristics has been investigated in table 2. no significant relationship was found between job stress and demographic characteristics (p-value> 0.05). 3.4. job satisfaction the level of job satisfaction was moderate in 61.1%, low in 22.2%, and high in 16.7% of the nurses. the relationship between job satisfaction and demographic characteristics showed that age had a significant relationship with job satisfaction (p = 0.039). there was a significant and positive correlation between age and job satisfaction score (p = 0.027, r = 0.3). job satisfaction increased with increase in age, as was also confirmed by post hoc tests. however, other demographic variables did not show any significant relationship with job satisfaction (table 2). 3.5. correlation of job stress, satisfaction, and burnout examining the relationship between the main variables showed a significant correlation between the three main variables. job burnout was directly correlated with job stress so that burnout rate increased with job stress increasing (p ≤0.001, r = 0.57). on the other hand, job burnout was negatively correlated with job satisfaction, indicating that with increase in the level of job satisfaction, the rate of burnout decreased (p = 0.001, r = -0.41). there was a negative correlation between job satisfaction and job stress (p ≤0.001, r = -0.43, table 3). 4. discussion the findings showed that more than 60% of the studied emergency nurses had moderate levels of job burnout, stress, and satisfaction. significant correlation was found between job burnout and marital status, as well as job satisfaction and older age. job burnout had direct correlation with job stress and indirect correlation with job satisfaction. there is a shortage of nursing staff around the world and iran is no exception. according to a census (2014), iran (with a population of 75 millions) requires about 240000 nursing staff; however, the number of nursing staff in iran now is about 100000 (24). majidi et al. (2017) concluded that the number of patients referred to the emergency department has increased following the implementation of the health system reform plan (25). in such a situation, maintenance of human resources in hospitals was a priority and nurses who were pioneers in terms of providing services to patients were exposed to high workload and consequently burnout and dissatisfaction. in support of this claim, nakhaei et al. in 2017 indicated that the low level of nursing staff satisfaction with the health system reform plan was due to the increase in the number of patients (26). hence, an investigation of job burnout seems to be of essence. aiken et al. proved that each additional patient per nurse was associated with a 23% increase in the odds of burnout and 15% increase in the odds of job dissatisfaction (6). in the emergency departments of the hospitals evaluated in this study, a large number of nursing staff had a low and moderate level of burnout and only 1.4% of the nursing staff had a high level of burnout. despite the fact that a small number of nurses reported high burnout levels, 76% of nurses revealed a moderate level of burnout and this should receive more attention. there are similarities and differences between the findings in this study and the results of some other studies. like the current study, some studies announced a moderate level of burnout. in 2016, tarcan et al. surveyed 250 emergency service staff. in this study, the burnout level was evaluated to be moderate (27). job burnout had a significant relationship with the employthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. tavakoli et al. 4 table 2: relationship of job burnout, stress and satisfaction with demographic variables of the nursing staff variable stress p satisfaction p burnout p sex female 3.03 ± 0.49 0.66 2.95 ± 0.66 0.75 4.01 ± 0.82 0.3 male 2.98 ± 0.44 2.9 ± 0.63 3.79 ± 0.98 marital status single 3.04 ± 0.32 0.554 3.1 ± 0.63 0.134 4.14 ± 0.58 0.049 married 2.98 ± 0.52 2.85 ± 0.64 3.78 ± 0.98 educational level diploma 3.16 ± 0.45 2.79 ± 0.76 3.83 ± 0.99 associate degree 2.93 ± 0.53 2.8 ± 0.62 4.12 ± 4.12 bachelor 2.98 ± 0.46 0.362 3.01 ± 0.62 0.635 3.91 ± 3.91 0.48 ma 3.51 ± 0.61 2.54 ± 0.61 4.91 ± 4.91 phd 2.77 ± na 2.61 ± na 4 ± na age (year) 23-32 3.04 ± 0.45 2.9 ± 0.61 3.97 ± 0.71 33-42 2.97 ± 0.52 0.582 2.86 ± 0.66 0.039 3.79 ± 1.05 0.61 43-54 2.97 ± 0.55 3.53 ± 0.43 3.62 ± 1.09 work experience (year) 1-7 3.07 ± 0.51 2.86 ± 0.66 4.14 ± 0.87 8-14 2.91 ± 0.5 0.704 2.95 ± 0.58 0.119 3.72 ± 0.72 0.184 15-21 3.02 ±0.26 2.88 ± 0.76 3.45 ± 1.26 22-28 2.86 ± 0.67 3.61 ± 0.42 3.67 ± 1.02 table 3: correlation between job burnout, job stress, and job satisfaction among studied nurses variables stress satisfaction burnout stress correlation 1 -0.43 0.57 p-value — ≤0.001 ≤0.001 satisfaction correlation -0.43 1 -0.41 p-value ≤0.001 — 0.001 burnout correlation 0.57 -0.41 1 p-value ≤0.001 0.001 — ees’ marital status and the level of burnout in single employees was higher than that in married ones. many studies have counted being single as a risk factor for burnout in nurses (27-30). seo et al. found that single nurses are 6 times more likely than married nurses to feel burnout (31). according to the findings of this study, there was a significant relationship between the nursing staff’s age and job satisfaction and their job satisfaction improves with increase in age. this result was in line with the findings of two other studies, both of which were carried out on nurses at the emergency department (27, 32). according to the findings, burnout had a significant reverse correlation with job stress. such a relationship is confirmed by various studies in different fields (28, 33, 34). a point to be noted is that high level of job stress among the staff does not necessarily imply having burned out staff. various investigations have shown that job satisfaction plays a critical role in moderating the effect of stress on resulting in job burnout (30). job burnout had a significant and inverse correlation with job satisfaction of the nursing staff in the emergency departments so that burnout rates increased linearly with a decrease in job satisfaction. a majority of studies had found similar results to the findings of this study (27-29, 32, 34). 5. conclusion the findings showed that more than 60% of studied emergency nurses had moderate levels of job burnout, stress, and satisfaction. a significant correlation was found between job burnout and marital status, and also between job satisfaction and nurses’ older age. job burnout had direct correlation with job stress and indirect correlation with job satisfaction. planning to reduce burnout of the emergency nursing staff seems to be necessary. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e41 6. appendix 6.1. acknowledgements none. 6.2. author contribution all authors made substantial contributions, revised the manuscript, and approved the final version for publication. tavakoli n, hosseini kasnavieh s m, soltani s and abbasi m: conception and design of the study. amini m: analysis. tahmasebi a: data collection. amini m and hosseini kasnavieh s m: first draft writing and preparing illustrations. 6.3. funding/support none. 6.4. conflict of interest none to declare. references 1. jonsson a, halabi j. work related post-traumatic stress as described by jordanian emergency nurses. accident and emergency nursing. 2006;14(2):89-96. 2. well e, first f, dignity p, it out w, training cb. stress in emergency departments: experiences of nurses and doctors. emergency nurse. 2011;19(4). 3. canadas-de la fuente ga, vargas c, san luis c, garcia i, canadas gr, emilia i. risk factors and prevalence of burnout syndrome in the 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noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency. 2018; 6 (1): e44 ca s e re p o rt hyper acute quadriplegia with chronic lead toxicity; a case report mehdi mesri1, fares najari2∗, ideh baradaran kayal3, dorsa najari4 1. quran and hadith research center life style institute, baqiyatallah university of medicaid sciences, tehran, iran. 2. toxicologist and forensic medicine department, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. legal medicine organization of alborz, karaj, iran. 4. medical faculty, shahid beheshti university of medical sciences, tehran, iran. received: may 2018; accepted: july 2018; published online: 15 july 2018 abstract: industrial lead toxicity is more common among miners. this type of toxicity occurs in two forms: acute and chronic. chronic toxicity is associated with different levels of brain dysfunction, motor impairment, cognitive dysfunction, and neuropsychiatric problems, including depression, anxiety, irritability, and emotional disorders. however, quadriplegia induced by chronic toxicity is very rare. here we report a 37-year-old male patient with a history of desert hunting, where he used to roll lead bullets in his mouth, who was admitted with sensory impairment, muscle weakness, and quadriplegia and final diagnosis of lead toxicity. keywords: lead poisoning, nervous system, adult; quadriplegia; emergency service, hospital; case report © copyright (2018) shahid beheshti university of medical sciences cite this article as: mesri m, najari f, baradaran kayal i, najari d. hyper acute quadriplegia with chronic lead toxicity; a case report . 2018; 6 (1): e44. 1. introduction industrial lead poisoning is one of the oldest types of occupational poisoning, which dates back to at least 5000 years ago. nonorganic lead can be found in workers of ceramic glaze, food canning, color, and cosmetic companies. there is also nonorganic lead in drinking water, industrial dust, and motor vehicle exhaust. lead levels are higher among adult workers who are in contact with industrial lead. this type of lead is mainly absorbed through the lungs and gastrointestinal tract (1, 2). neurotoxicity occurs due to physiological and neurological changes, which are caused by exposure to toxic agents. it may cause changes in cognition, memory, and mood or result in the development of psychiatric disorders (3). neurotoxicity induced by heavy metals, including lead, mercury, and arsenic, has been explored more. this type of toxicity has two common forms: acute and chronic. symptoms of acute poi∗corresponding author: fares najari; department of forensic medicine, shahid beheshti university of medical sciences, daneshjou boulevard, arabi ave, velenjak, tehran, iran. p.o.box: 1983969411. email: najari.hospital@sbmu.ac.ir tel: 00989123195140 soning include nausea, headache, cognitive problems, and emotional disorders. chronic exposure often occurs in industrial workplaces. in chronic exposure, symptoms are mostly neurological and psychiatric, including depression, anxiety, and irritability. chronic exposure to lead may cause symptoms, such as fatigue, brain dysfunction, motor impairment, and cognitive dysfunction in general (4). studies show that reduction of sensory responses and cognitive impairment occur in male workers with blood lead levels ≥ 40 µg/100ml (5). peripheral motor neuropathy and reduced velocity of peripheral nerve conduction have been also reported in some cases of chronic lead toxicity (6, 7). at high doses, lead toxicity causes irritability, headache, mental fatigue, reduced concentration, memory loss, tremor, and hallucinations. it may even result in quadriplegia, seizure, delirium, coma, or death. in the event of lead toxicity, early diagnosis, careful evaluation, and immediate treatment are very important (8). therefore, it is necessary to be familiar with the rare symptoms of chronic lead toxicity. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. mesri et al. 2 2. case presentation the patient was a 37-year-old married man, who was a hunter of wild desert animals and used to roll lead bullets in his mouth. in the spring of 2015, he was referred to the hospital with abdominal pain and tenderness which had initiated almost 30 days before his admission. the patient was admitted to the surgical gastroenterology department due to abdominal pain and tenderness, weight loss, loss of appetite, and diffuse itching. on the tenth day of hospitalization, the patient suddenly developed sensory impairment, muscle weakness, and quadriplegia. with suspicion to super acute toxicity, he was transferred to the poisoning department. the results of abdominal and pelvic computed tomography (ct) scans were normal, just like the results of endoscopy and colonoscopy. moreover, the results of doppler ultrasound and brain magnetic resonance imaging (mri) were normal. electromyography (emg) and nerve conduction velocity (ncv ) suggested axonal neuropathy in all the limbs. the patient’s neurological symptoms, such as motor neuropathy, quadriplegia, walking disability, and paresthesia, were exacerbated since the time of admission. cognitive disorders, including thought disorders, accompanied by distress, anxiety, and delirium, were evident in the patient. laboratory findings showed increased levels of liver enzymes (ast: 220 unit/l, alt;120 unit/l), bilirubin(total: 3 mg/dl with direct: 1/2 mg/dl), lactate dehydrogenase (ldh: 750 unit/l), amylases (220 unit/l), leukocytosis (22000/m3), and anemia (mean hemoglobin: 8.5 g/dl, mcv: 75). no basophilic stippling was observed in the peripheral blood smear during hospitalization. the patient’s medical history indicated chronic abdominal pain about four years before his referral for which he was hospitalized for several days and was discharged with a good general condition. with suspicion of lead toxicity the serum lead level was measured, which indicated a lead level of 150 µcg/dl. considering the likelihood of acute lead poisoning with repeated attacks, chelation therapy was applied according to the standard protocols of the medical toxicology book. therapeutic instructions included livergol tablets, adenosine monophosphate (amp), bronchoalveolar lavage (bal), ethylenediaminetetraacetic acid (edta), calcium, and sodium. during treatment with bal, the patient experienced stress disorders, exacerbated delirium, and tachycardia. methadone was initiated to overcome the suspected drug withdrawal syndrome. however, the symptoms did not resolve, and sedative medications such as midazolam were used to manage them. after two days of treatment with bal, which led to restlessness, distress, and tachycardia, bal treatment was temporarily terminated. after stabilization, bal was continued in the intensive care unit (icu). bal was continued with the same dosage as the patient was hospitalized in the icu. his general condition gradually improved, and bal-induced complications (tachycardia, hypertension, and distress), which persisted for three to five days, were resolved. once the lead level reached 120 µcg/dl, treatment was continued with etda+bal with the same dosage. after three days of treatment, the lead level reached 85 µcg/dl. therefore, bal was terminated and substituted with oral succimer. after three days of treatment with succimer, the lead level reached 65 µcg/dl. at this lead level, bal and edta administration was terminated, and succimer was continued with the same dosage. during treatment, the ferritin level became normal. after 15 days of treatment, the patient’s anemia was improved and the level of liver enzymes gradually decreased and eventually reached the normal level after three weeks of treatment. after four months of treatment with succimer, the lead level reached 60 µcg/dl; treatment continued with succimer (divided doses every 12 hours). however, neurological symptoms, specifically muscle weakness and neuropathy, remained unchanged. with proper physiotherapy, most disorders, including muscle weakness of the upper and lower extremities, improved. after one year of follow-up, he was completely alert, without any neurological deficits; his cognition and perception also improved. 3. discussion several studies have shown that industrial lead exposure can cause memory impairment and reduce the processing speed, reading comprehension, motor skills, and executive functions. moreover, anxiety, depression, and phobia are probable in these patients. in our study, the patient suffered from tremor, paresthesia, peripheral neuropathy, quadriplegia, and walking disability. in a case report by beig mohammadi et al., entitled “quadriplegia induced by lead-contaminated opium”, a patient was examined with quadriplegia. despite the resolution of all symptoms and reduction of blood lead level, the patient was discharged with quadriplegia (9). in the present report, which is only different from the mentioned study in terms of the contamination source, the patient was completely recovered after the treatment period and oneyear follow-up. a study by d. a. gidlow showed that in industrial workers with lead levels above 40 µg/100ml, neurotoxicity was characterized by motor deficiency and cognitive problems and even in some cases by peripheral neuropathy. memory and concentration problems, besides visual impairment, occur at lead levels higher than 50 µg/100ml (1). a study by sansar w, which was conducted on mice, found that lead levels of 100 µg/100ml can cause changes in the glial and neuronal systems and result in functional and behavioral impairments this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e44 (10). in a study of 2930 cases, robert a. goyer concluded that infants, whose umbilical cord blood lead levels were higher than 10 µg/100ml, had sensory, motor, and visual impairments, as well as cognitive problems during development (11). moreover, in a review study, lisa h. mason concluded that high levels of lead toxicity in workers cause seizure, lethargy, and coma. in acute cases of lead toxicity, reversible neuropathy occurs (8). in another study, wilhelm m found that cognitive and behavioral changes occur at a lead level of 100 µg/100ml; these disorders were more serious in younger patients (12). in our study, long-term lead exposure and high lead level resulted in neuropathy, numbness, and quadriplegia, which gradually resolved with proper chelation therapy. moreover, in a study on industrial workers baker el found that workers with lead levels above 40 µg/100ml experienced problems, such as mood and emotional disorders, exacerbated depression, confusion, anger, and increased tension and fatigue. in the long run, these workers experienced complications, such as memory, cognitive, visual, and verbal impairments (13). in this study, motor problems were not reported. slight motor problems have been reported in several studies, although quadriplegia and walking disability were not found in the literature; quadriplegia was only reported in some cases. in this study, we reported a patient with a lead level of 150 µg/100ml, associated with quadriplegia and walking disability. 4. conclusion: workers who are in contact with industrial lead are exposed to chronic lead toxicity. delayed detection of serious symptoms, such as cognitive, sensory, and functional disorders, can be life-threatening for these workers. therefore, workers exposed to industrial lead are recommended to undergo periodic and regular examinations to prevent any possible complications. 5. appendix 5.1. acknowledgements we would like to express our special thanks to the forensic center of tehran, iran. 5.2. author’s contribution all authors meet the four criteria of authorship contribution based on the recommendations of the international committee of medical journal editors. 5.3. conflict of interest the authors declared no potential conflict of interest. 5.4. funding none. references 1. gidlow d. lead toxicity. occupational medicine. 2004;54(2):76-81. 2. papanikolaou nc, hatzidaki eg, belivanis s, tzanakakis gn, tsatsakis am. lead toxicity update. a brief review. medical science monitor. 2005;11(10):ra329-ra36. 3. tandon s, chatterjee m, bhargava a, shukla v, bihari v. lead poisoning in indian silver refiners. science of the total environment. 2001;281(1-3):177-82. 4. mason lh, mathews mj, han dy. neuropsychiatric symptom assessments in toxic exposure. psychiatric clinics. 2013;36(2):201-8. 5. majchrzak m, celinski r, kowalska t, sajewicz m. fatal case of poisoning with a new cathinone derivative: α-propylaminopentiophenone (n-pp). forensic toxicology. 2018:1-9. 6. rubens o, logina i, kravale i, eglite m, donaghy m. peripheral neuropathy in chronic occupational inorganic lead exposure: a clinical and electrophysiological study. journal of neurology, neurosurgery & psychiatry. 2001;71(2):200-4. 7. wu m-l, deng j-f, lin k-p, tsai w-j. lead, mercury, and arsenic poisoning due to topical use of traditional chinese medicines. the american journal of medicine. 2013;126(5):451-4. 8. mason lh, harp jp, han dy. pb neurotoxicity: neuropsychological effects of lead toxicity. biomed research international. 2014;2014. 9. baigmohammadi m, mohammadi m, mahmoodpour a, karvandian k, aghdashi m. quadriplegia due to leadcontaminated opium&58; a case report. tehran university medical journal. 2008;66(7):521-4. 10. sansar w, ahboucha s, gamrani h. chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat. acta histochemica. 2011;113(6):601-7. 11. goyer ra. results of lead research: prenatal exposure and neurological consequences. environmental health perspectives. 1996;104(10):1050. 12. wilhelm m, heinzow b, angerer j, schulz c. reassessment of critical lead effects by the german human biomonitoring commission results in suspension of the human biomonitoring values (hbm i and hbm ii) for lead in blood of children and adults. internathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. mesri et al. 4 tional journal of hygiene and environmental health. 2010;213(4):265-9. 13. baker el, feldman rg, white rf, harley jp, dinse ge, berkey cs. monitoring neurotoxins in industry: development of a neurobehavioral test battery. journal of occupational medicine: official publication of the industrial medical association. 1983. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion conclusion: appendix references emergency. 2018; 6 (1): e23 ca s e re p o rt hopkins syndrome in a 14 year old boy; a case report alireza majidi1, sasan saket2, zohreh nabizadeh gharghozar3, ehsan akrami2, seyed mohsen fayyazi1∗ 1. emergency department, shohadaye tajrish hospital, shahaid beheshti university of medical sciences, tehran, iran. 2. pediatric neurology research center, shahaid beheshti university of medical sciences, tehran, iran. 3. school of nursing and midwifery, kashan university of medical sciences, kashan, iran. received: august 2017; accepted: january 2018; published online: 16 april 2018 abstract: hopkins syndrome (hs) is a flaccid paralysis resembling poliomyelitis that has been seen in some children who are recovering from an acute episode of asthma. this syndrome should be suspected based on clinical findings even before the occurrence of characteristic breathing patterns and epilepsy. we report a 14-year-old boy who had experienced an episode of hs. keywords: pitt-hopkins syndrome; nervous system diseases; rare diseases; asthma © copyright (2018) shahid beheshti university of medical sciences cite this article as: majidi a, saket s, nabizadeh gharghozar z, akrami e, fayyazi sm. hopkins syndrome in a 14 year old boy; a case report. emergency. 2018; 6 (1): e23. 1. introduction in some children recovering from an acute episode of asthma, a flaccid paralysis resembling poliomyelitis has been encountered (1-3). this condition, first reported from australia in 1974, has been termed hopkins syndrome (hs) (4). no consistent virus has been cultured from such patients, who have generally been successfully vaccinated against poliomyelitis (5). the disorder primarily affects the anterior horn cells. a rapid progression of paralysis usually affects one limb, leaving the child with a severe and permanent weakness. sensation is preserved; the cerebrospinal fluid (csf) usually shows moderate mononuclear pleocytosis, and the protein content can be slightly elevated (6-8). magnetic resonance imaging (mri) changes in the anterior horn have been documented (9). some of the children have shown evidence of an underlying immune deficiency (10). we report a 14year-old boy who had experienced an episode of hs. 2. case presentation: a 14-year-old boy with a history of asthma since being 2 years old was admitted to hospital with history of seizure and loss of consciousness. there was a history of common cold in the ∗corresponding author: seyed mohsen fayyazi; emergency department, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. tel: 00989306224313 email: mfayyazib@yahoo.com patient a week before and he had experienced severe shortness of breath 4 days before admission. no significant history of trauma was recorded. his mother had a history of abortion. his mother had no certain disease during and before being pregnant with him. he had used atrovent and salbutamol sprays. no family history of similar illness was present. at the time of admission, vital signs were as follows: temperature 37.8 ◦c, pulse 131 beats per minute, respiratory rate 26 per minute and blood pressure 90/50 mmhg. on physical examination, he was confused and there was bilateral expiratory wheezes as well as scattered rhonchi in the lower lobes. his thoracic x-ray was normal. the neurologic examination results were normal. his complete blood count was as follows: 25,600 white cells/mm3, with 81% neutrophils, 2% eosinophils, 15% lymphocytes, and 3.0% monocytes, erythrocyte sedimentation rate (esr) was (8, 0-10 mg/dl), c-reactive protein (crp) was (4.1 mg/dl, 0-6 mg/dl), ph= 7.59, po2= 96.5, hco3= 25.9 mmol/l, and o2sat=94%. other routine laboratory test results were normal. the antiviral antibodies in paired serum samples showed no significant changes in any of the examined viruses, including herpes 1 and 2, echovirus, enterovirus, coxsackievirus, and poliovirus types 1, 2, and 3. torch, anti-mycoplasma, and anti-borrelia titers were normal. hbs ag, abs ab, hcv ab and hiv ab were negative. the cerebrospinal fluid cultures were negative. no cardiac abnormalities were noted on clinical and ultrasound examinations. the sleeping eeg showed anomalies in the frontocentral regions with left prevalence and tendency toward this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. majidi et al. 2 contralateral diffusion. abdominal ultrasound and computed tomography (ct) scans were normal. his brain mri was normal. with suspition to pitt-hopkins syndrome acyclovir 400 mg was prescribed. he experienced no other asthma and seizure attack. during a 5-month follow-up from the episode there were no new clinical symptoms. 3. discussion hopkins syndrome is a rare disease affecting anterior horn cells following an acute asthma attack, most often in children that have atopic asthma (11). generally, this disease manifests from several days to a few weeks after an acute attack of asthma, presenting as the acute onset of flaccid paralysis, and in most cases progresses to severe muscle atrophy in the affected limb (12). based on previous studies, in such episodes, there is a poor response to corticosteroids and usually there are no recurrences (13). some cases have predominant ventral root involvement on mri, while other cases exhibit an extension of the lesions into the anterior columns (14-16). therefore, the site of lesions in hs is not strictly limited to the anterior horn. in some of the previous studies it was reported that peripheral blood lymphocytes of patients with asthma express more cytokine on stimulation with allergens compared to those with skin allergy (17), but currently there is no evidence-based clinical correlation between cytokine production and hopkins syndrome. atopic myelitis (am) is a clinical entity with similarity to hopkins syndrome. many reports have confirmed the presence of evidence in the central nervous system or peripheral nervous system in patients with a high level of total ige and co-existing atopic disease (18). hs and am differ from each other in the preferential age of onset, neurologic manifestations, and preferential sites of spinal cord involvement. however, both conditions are similar regarding the most important point that myelitis develops in the presence of atopic disorders, which suggests a link between atopy and the development of spinal cord inflammation. both of them could be an allergic mechanism due to cross reactivity between an allergen and cns or pns. kira et al. described 22 patients with myelitis of unknown etiology and atopic diathesis, 5 of whom showed focal amyotrophy in one or two limbs (16). hopkins syndrome is frequently associated with epilepsy. previous reports do not include detailed eeg descriptions, but slow-wave activity was reported in the patients of pitt and hopkins (1978), whereas in singh’s (1993) patient, there was “generalized epileptogenic activity”. horiuchi et al. described a 22-year-old woman who showed an additional episode of myelitis after another asthma attack, although no relapse has ever been reported in hs cases (4, 19, 20). joubert syndrome, rett syndrome and angelman syndrome should be considered as differential diagnoses in patients with the same symptoms as our patient (21). 3.1. conclusion: hopkins syndrome should be suspected based on clinical findings even before the occurrence of typical breathing patterns and epilepsy. 4. appendix 4.1. acknowledgements all the staff members of the emergency department of shohaday-e-tajrish hospital are thanked for their cooperation throughout the study period. 4.2. authors contribution all authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declare that there is no conflict of interest in any phase of performing the study. 4.4. funding none. references 1. hopkins i. a new syndrome: poliomyelitisâăřlike illness associated with acute asthma in childhood. journal of paediatrics and child health. 1974;10(5):273-6. 2. yeung sc, antonio g, ip ks. flaccid paralysis of the limbs after an asthmatic attack. pediatric neurology. 2010;42(2):133-6. 3. leonardi m, sartorius n, hull hf, ward na, organization wh. acute onset flaccid paralysis. 1993. 4. horiuchi i, yamasaki k, osoegawa m, ohyagi y, okayama a, kurokawa t, et al. acute myelitis after asthma attacks with onset after puberty. journal of neurology, neurosurgery & psychiatry. 2000;68(5):665-8. 5. fine pe, carneiro ia. transmissibility and persistence of oral polio vaccine viruses: implications for the global poliomyelitis eradication initiative. american journal of epidemiology. 1999;150(10):1001-21. 6. tyler kl. acute viral myelitis. infections of the central nervous system. 2004:310-1. 7. sejvar jj, leis aa, stokic ds, van gerpen ja, marfin aa, webb r, et al. acute flaccid paralysis and west nile virus infection. emerging infectious diseases. 2003;9(7):788. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e23 8. marx a, glass jd, sutter rw. differential diagnosis of acute flaccid paralysis and its role in poliomyelitis surveillance. epidemiologic reviews. 2000;22(2):298-316. 9. chen c-y, chang y-c, huang c-c, lui c-c, lee k-w, huang s-c. acute flaccid paralysis in infants and young children with enterovirus 71 infection: mr imaging findings and clinical correlates. american journal of neuroradiology. 2001;22(1):200-5. 10. shahmahmoodi s, mamishi s, aghamohammadi a, aghazadeh n, tabatabaie h, gooya mm, et al. vaccineassociated paralytic poliomyelitis in immunodeficient children, iran, 1995âăş2008. emerging infectious diseases. 2010;16(7):1133. 11. piero p, longo mr, scalia f, polosa r, kira j-i, falsaperla r. recurrent hopkin’s syndrome: a case report and review of the literature. journal of the neurological sciences. 2010;297(1):89-91. 12. shapiro gg, chapman jt, pierson we, bierman cw. poliomyelitis-like illness after acute asthma. the journal of pediatrics. 1979;94(5):767-8. 13. shahar em, hwang pa, niesen ce, murphy eg. poliomyelitis-like paralysis during recovery from acute bronchial asthma: possible etiology and risk factors. pediatrics. 1991;88(2):276-9. 14. danta g. electrophysiological study of amyotrophy associated with acute asthma (asthmatic amyotrophy). journal of neurology, neurosurgery & psychiatry. 1975;38(10):1016-21. 15. liedholm lja, eeg-olofsson o, ekenberg bek, nicolaysen rb, torbergsen t. acute postasthmatic amyotrophy (hopkins’ syndrome). muscle & nerve. 1994;17(7):769-72. 16. kira j-i, isobe n, kawano y, osoegawa m, ohyagi y, mihara f, et al. atopic myelitis with focal amyotrophy: a possible link to hopkins syndrome. journal of the neurological sciences. 2008;269(1):143-51. 17. kimura m, tsuruta s, yoshida t. differences in cytokine production by peripheral blood mononuclear cells (pbmc) between patients with atopic dermatitis and bronchial asthma. clinical and experimental immunology. 1999;118(2):192. 18. osoegawa m, ochi h, yamada t, horiuchi i, murai h, furuya h, et al. high incidence of subclinical peripheral neuropathy in myelitis with hyperlgeaemia and mite antigen-specific ige (atopic myelitis): an electrophysiological study. internal medicine. 2002;41(9):684-91. 19. kira j-i, kawano y, yamasaki k, tobimatsu s. acute myelitis with hyperigeaemia and mite antigen specific ige: atopic myelitis. journal of neurology, neurosurgery & psychiatry. 1998;64(5):676-9. 20. kira j-i, kawano y, horiuchi i, yamada t, imayama s, furue m, et al. clinical, immunological and mri features of myelitis with atopic dermatitis (atopic myelitis). journal of the neurological sciences. 1999;162(1):56-61. 21. taddeucci g, bonuccelli a, mantellassi i, orsini a, tarantino e. pitt-hopkins syndrome: report of a case with a tcf4 gene mutation. italian journal of pediatrics. 2010;36(1):12. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 96 emergency (2014); 2 (2): 96-97 case report a 55-year old man with acute painful flank mass, a case report aida alavi-moghaddam1, reza shirvani2, mahmoud yousefifard3, mostafa alavi-moghaddam2* 1. faculty of medicine, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 3. department of physiology, school of medicine, tehran university of medical sciences, tehran, iran abstract lumbar hernias (lh) accounts for less than 1.5% of total hernia incidence. it can occur in two separate triangular areas of the flank. about 300 cases have been reported in the literature. here, we report a 55-year old man with acute painful left side flank mass and final diagnosis of lh. the mass was appeared about three hours before admission and his pain was slight at first but became more severe gradually. he had stable vital sign and the only positive finding on his physical examination was the sphere shape, firm, mobile, and mild tender mass at his left flank. key words: hernia; flank pain; case report cite this article as: alavi-moghaddam a, shirvani r, yousefifard m, alavi-moghaddam m. a 55-year old man with acute painful flank mass, a case report. emergency. 2014;2(2):96-7. introduction:1 umbar hernias (lh) are rare; about 300 cases have been reported. it can occur in two separate triangular areas of the flank (1-3). the superior triangle (grynfeltt's lumbar triangle) is bound by the 12th rib superiorly, the internal oblique muscle inferiorly, and the sacrospinous muscles medially. the inferior triangle (petit's lumbar triangle) is bound by the latissimus dorsi muscle posteriorly, the external oblique muscle anteriorly, and the iliac crest inferiorly (4). lhs are more common on the left side. this may be because the liver pushes the right kidney inferiorly in development, leading to the protection of the lumbar triangles (5). lh may contain a number of intra or retroperitoneal structures including large intestine, small intestine, stomach, kidney, spleen, and mesentery omentum. 25% of all lhs are secondary acquired that may be caused by blunt-penetrating or crushing trauma; fractures of the iliac crest; surgical lesion; hepatic abscesses; infection in pelvic bones, and ribs or lumbodorsal fascia (1) . incisional hernias develop in 3.8%-11.5% of cases after abdominal –surgical procedures (6). the incidence depends on a number of risk factors including old age, sex, obesity, suture type and wound infection. here, we report a 55-year old man with acute painful left side flank mass. *corresponding author: mostafa alavi-moghaddam; imam hosein hospital, shahid madani ave, tehran, iran. phone/fax: +989125597918. email: mosalavi@yahoo.com received: 9 february 2014; accepted: 21 march 2014 case report: a 55-year-old homeless man came to the emergency department (ed) with pain and a mass in his left flank. the patient was awake and oriented. this mass was appeared about three hours before admission and his flank pain was slight at first but became more severe gradually. on admission, he had 18 per minute respiratory rate, 88 per minute pulse rate, 110/80 mmhg blood pressure, 90% o2 saturation in room air, and 37°c auxiliary temperature. the pain score was about 9 to 10 according to visual analog scale (vas). the only positive finding on physical examination was the sphere shaped, firm, mobile, and mild tender mass at his left flank (figure 1). there was a 5 cm scar on this site because of previous penetrating trauma injury due to a motor vehicle collision. there was an abdominal wall defect about 8 cm in diameter and bowel loop was trapped in the neck of hernia sac on computed tomography (ct) (figure 2). as a result, a petit's triangle lh was diagnosed. surgery was performed immediately by diagnosis of strangulated lh. finally, the report of surgery finding confirmed diagnosis. discussion: lh accounts for less than 1.5% of the total hernia incidence (7). the inferior lumbar hernia is less common because of attachment of external oblique and latissmus dorsi to the iliac crest. lumbar hernia could be divided into two groups congenital and acquired (8). congenital lh accounts for 20% of all lhs. congenital lh usually could be seen in superior lumbar triangle. complical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2014 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 97 alavi-moghaddam et al tions oflh include irreducibility, incarceration and strangulation (9). in lh symptomatology limited to lower back pain. in less than 10% of cases the onset is acute with bowel obstruction (10). treatment depends on the size and type of hernia. if the defect is small, it can be closed with continuous polypropylene. for large defect, preperitoneal meshplasty is the best treatment. laparoscopic repair has been used in different reports with less pain and good functional result (11). motor vehicle accidents are the most common cause of posttraumatic lhs (1, 4). if a lh is found after a motor vehicle accident, it is critical to assume that the patient has other intra-abdominal injuries. these patients should undergo urgent laparotomy because more than 60% of them will have major intra-abdominal injuries. acknowledgments: we would like to thank mohammad reza sohrabi for his valuable helps. also, thanks to the patient's permission to use photos. conflict of interest: none funding support: none authors’ contributions: all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. references: 1. abrahamson j. postoperative ventral abdominal hernia. in: zinner mj, schwartz si, editors. hernias. 10 ed. stanford: appleton and lange; 1990. p. 479–580. 2. astarcioglu h, sokmen s, atila k, karademir s. incarcerated inferior lumbar (petit's) hernia. hernia. 2003;7(3):158-60. 3. baratloo a, safari s, rouhipour a, et al. the risk of venous thromboembolism with different generation of oral contraceptives; a systematic review and meta-analysis. emergency. 2014;2(1):1-11. 4. bohn d. congenital diaphragmatic hernia. am j respir crit care med. 2002;166(7):911-5. 5. bucknall t, cox p, ellis h. burst abdomen and incisional hernia: a prospective study of 1129 major laparotomies. br med j (clin res ed). 1982;284(6320):931. 6. dinger j, assmann a, möhner s, do minh t. risk of venous thromboembolism and the use of dienogest and drospirenone containing oral contraceptives: results from a german casecontrol study. j fam plann reprod health care. 2010;36(3): 123-9. 7. gronich n, lavi i, rennert g. higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. can med assoc j. 2011;183(18):e1319-e25. 8. hegarty m, bryer j, angorn i, baker l. delayed presentation of traumatic diaphragmatic hernia. ann surg. 1978;188(2): 229. 9. le neel j, sartre j, borde l, guiberteau b, bourseau j. lumbar hernias in adults. apropos of 4 cases and review of the literature. j chir (paris). 1993;130(10):397-402. [french]. 10. manzoli l, de vito c, marzuillo c, boccia a, villari p. oral contraceptives and venous thromboembolism. drug saf. 2012;35(3):191-205. 11. wiechmann rj, ferguson mk, naunheim ks, et al. laparoscopic management of giant paraesophageal herniation. ann thorac surg. 2001;71(4):1080-7. figure 1: the patient’s left flank mass  figure 2: abdominal computed tomography of patients archives of academic emergency medicine. 2019; 7 (1): e16 or i g i n a l re s e a rc h effects of supplementation and training on ameliorating lipid profiles and protection against coronary artery disease; an experimental study reza vafaee1,2, hamid soori3, mehdi hedayati4, hamid reza hatamabadi5∗ 1. safety promotion and injury prevention research center, student research committee, shahid beheshti university of medical sciences, tehran, iran. 2. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. 3. safety promotion and injury prevention research center, school of public health, shahid beheshti university of medical sciences, tehran, iran. 4. cellular and molecular endocrine research center, research institute for endocrine sciences, shahid beheshti university of medical sciences, tehran, iran. 5. safety promotion and injury prevention research center, department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: november 2018; accepted: december 2018; published online: 12 february 2019 abstract: introduction: the use of antioxidants may reduce the harmful effects of radicals during exercise and extreme sports. the current study aimed to investigate the effect of this supplement on the lipid profiles in exerciseinduced muscle injury. methods: in this experimental study, 64 wistar rats were randomly divided into four groups of control, exercise, exercise+resveratrol (rev ) and rev. after a week of adaptation, endurance and acute exercises were conducted in a motor driven treadmill, followed by using a training protocol in which running speed was gradually elevated until 19 weeks of age. finally, the levels of cholesterol (cho), triglycerides (tg), low-density lipoproteins (ldl), high-density lipoproteins (hdl), and very low-density lipoproteins (vldl) were compared between the groups. results: there was no statistically significant difference in cho plasma level between the studied groups after acute and endurance exercises. there was a significant increase in the level of tg in the exercise group (p = 0.001) and the exercise+rev (p = 0.004) group after acute and endurance exercises. after the implementation of the endurance and acute exercises none of the studied groups had statistically significant changes in hdl plasma level. there was a significant decrease in ldl plasma levels in the exercise (p = 0.007) and the exercise+rev (p = 0.01) groups. after performing endurance protocol, vldl plasma levels increased significantly in the exercise (p = 0.001) and the exercise+rev (p = 0.005) groups in comparison with control group. conclusion: based on the findings, there was no difference in the level of cho and hdl between the training groups, rev and control groups. however, both endurance exercise and acute exercise trainings resulted in an increase in tg and vldl levels and decrease in ldl level, compared with the control group. keywords: resveratrol supplementation; lipid profiles; wistar rat; endurance and acute exercise trainings cite this article as: vafaee r, soori h, hedayati m, hatamabadi h. effects of supplementation and training on ameliorating lipid profiles and protection against coronary artery disease; an experimental study. arch acad emerg med. 2019; 7(1): e16. 1. introduction cardiovascular disease will cause more than 75% of deaths worldwide by 2020, if this trend continues, about 24.4 mil∗corresponding author: hamid reza hatamabadi; emergency department, imam hossein hospital, shahid madani avenue, imam hossein square, tehran, iran. email: hhatamabadi@yahoo.com lion people will die before 2030 (1, 2). physical inactivity emphasizes adverse outcomes such as atherosclerosis, diabetes, obesity, and metabolic syndrome. on the other hand, sports activities can be capable of reducing and preventing such diseases (3, 4). one of the most sensitive targets for peroxidants can be non-saturated fatty acids in biological membranes that interfere with the pathogenesis of many diseases. furthermore, cellular toxicity metabolites from lipid this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. vafaee et al. 2 peroxides play a significant role in the oxidation of proteins present in low-density lipoprotein (ldl). this trend is also important in the pathogenesis of atherosclerosis (5). physical activity can lead to a 1.8-fold increase in lipid peroxidation after 60 minutes of intense cycling exercise. on the other hand, the implementation of intense and prolonged exercise can also lead to functional impairment of immunity, inflammation, oxidative stress and muscle damage (6, 7). exercise-induced oxidative stress may be neutralized with antioxidants. antioxidants, even at very low concentrations, along with an oxidizing agent, prevent oxidation of this oxidizing agent and are capable of delaying it (8, 9). the use of antioxidants improves the antioxidant status of the body and may reduce the harmful effects of radicals during exercise and extreme sports (9, 10). resveratrol (rev ) has been introduced for the first time in the 1940s in the cassia quniquangulata. it has many therapeutic aspects and has been previously used in iran since around 6,000 years bc (11). the chinese and japanese used a plant called polygonum cuspidatum in the year 100 bc to treat many diseases. in the 1960s, rev was isolated from this plant (12). rev is a specific polyphenol compound and its antioxidant nature is high due to the presence of two phenolic rings on both sides of the double bond; indeed, this stilbenoid is one of the most potent antioxidants found in nature (13, 14). a number of reports suggested that co-administration of rev with statins was capable of increasing the cardio-protective effect of patients with cardiac arrhythmias. chen et al. revealed the inhibitory effect of rev on cardiac hypertrophy in 2008 (15). the supplementation of rev in prevention and treatment of cardiovascular diseases was initially investigated by controlling ldl, which is the main cause of atherosclerosis progression (16). rev protects the heart against myocardial damage following ischemia, and it has been shown that the supplementation of rev has improved cardiac function in hypertension induced in laboratory rats (17). considering the positive effect of rev on inhibiting oxidative stress and inflammatory response from free radicals, the present study was aimed to investigate the effect of this supplement on the lipid profiles in exercise-induced muscle injury. 2. methods 2.1. study design and setting this experimental study was performed in shahid beheshti university of medical sciences from february 2017 to march 2018. male wistar rats were randomly divided into four groups: control, exercise, rev, and exercise+rev and their lipid profiles were compared after interventions. all animals were enrolled in the study according to approved guidelines for care and use of laboratory animals. they were given a standard commercial diet that was purchased from pars animal feed company, iran. the protocol of the study was approved by the local ethical committee (ir.sbmu.msp.1396.372). 2.2. participants sixty-four male wistar rats (165–175 g; 6-weeks-old) were obtained from razi research institute of karaj, iran, and housed into standard conditions in groups of 4 animals per cage (18”× 10”× 8”) under a 12 h light/dark cycle, at 22 ± 3◦c, with a 45% relative humidity. overall, a total of 16 male wistar rats per group were included in the present study. 2.3. intervention male wistar rats in trained group were subjected to the familiarization step for one week exercising on a rodent treadmill for 10 minutes, three times a week, in which the running speed was set to 5 to 10 m/min. additionally, the control groups had access to the treadmill running three days during the week for 10 minutes, where exercise session was planned to be constant at a slow speed with an electrical stimulator. rev supplementation (10 mg/kg of rev in ethanol 2%/100 ml h2o) was began during exercise. on the other hand, those in the control group were also administered with water-containing ethanol 2% /100ml h2o as the vehicle. 2.4. exercise protocol after a week of adaptation, the rats began performing the protocol at 8 weeks of age. the training included endurance and acute exercises, which were conducted in a motordriven treadmill at a speed of 10 m/minute, 20 min/day for 5 days/week, followed by applying a training protocol in which running speed was gradually elevated to 30 m/min for 60 min/day until 19 weeks of age. it is noteworthy that exercise intensity was adjusted to 65% maximal oxygen uptake (vo2max) as described previously (18). the animals were sacrificed intra-peritoneally with 30-50 mg/kg ketamine and 3-5 mg/kg xylosin three days after the last exercise procedure for avoiding acute metabolic effects induced by the final run. between 7 and 10 ml of blood samples were obtained at sacrifice by cardiac puncture in a heparin-treated 10-ml syringe. after that, all samples were centrifuged for 15 min at 3000×g at 4◦c, and serum samples were immediately stored at – 20◦c until use. lipid profiles including cholesterol (cho), triglycerides (tg), low-density lipoproteins (ldl), high-density lipoproteins (hdl), and very lowdensity lipoproteins (vldl) were biochemically measured using commercially available kits according to the manufacturer’s protocols. 2.5. statistical analysis the data was collected by the first author. all data were processed and analyzed using ibm spss statistics ver. 21.0. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e16 figure 1: comparison of plasma triglycerides changes in acute exercise (a) and endurance exercise (b) groups. c = control group, t = train or exercise group, s = supplement or resveratrol, t+s = exercise+resveratrol. error bar = 95% confidence interval. for statistical evaluation of the changes in all groups, we applied one-way analysis of variance (anova). statistical significance was set at p<0.05. additionally, tukey’s test was applied for post-hoc comparisons. 3. results tables 1 and 2 compare the changes of lipid profile between different groups after acute and endurance exercises. 3.1. cho plasma levels there was no statistically significant difference in cho plasma level between the studied groups after acute and endurance exercises (tables 1 and 2). 3.2. tg plasma levels following the implementation of the endurance exercise protocols, there was a significant increase in the level of tg in the exercise group (p = 0.001) and the exercise+rev (p = 0.004) group compared to the control group, but no significant difference was found in terms of plasma tg levels between the exercise and exercise+rev groups (p = 0.450; table 1). on the other hand, a statistically significant increase was observed in plasma tg levels in the exercise (p < 0.001) and exercise+rev (p = 0.002) groups compared with the control group after performing acute protocol. however, the plasma tg levels in the rev group demonstrated a significant decrease compared to the exercise group (p < 0.001; table 2). there was a significant difference between the tg plasma level of exercise group after acute and endurance exercises (p = 0.03, figure 1). 3.3. hdl plasma levels as shown in tables 1 and 2; after the implementation of the endurance and acute exercise none of the studied groups had statistically significant changes in hdl plasma level. also, no statistically significant difference was revealed in the hdl plasma level between the groups undergoing endurance and acute exercises. 3.4. ldl plasma level there was a significant decrease in ldl plasma levels in exercise (p = 0.007) and exercise + rev (p = 0.01) groups compared to control group. after performance of the acute exercise, plasma ldl level showed a significant decrease in the exercise group compared with the control group (p = 0.049). there was no statistically significant difference in the ldl plasma levels between endurance and acute exercise groups. 3.5. vldl plasma levels after performing endurance protocol, vldl plasma levels increased significantly in the exercise (p = 0.001) and the exercise+ rev (p = 0.005) groups in comparison with control group. after implementation of the acute protocol, there was a significant increase in plasma vldl level in the exercise group (p < 0.0001) and the exercise+rev group (p = 0.002) when compared with the control group. however, vldl plasma levels in the exercise+rev exhibited a statistically significant difference compared to the exercise group (p = 0.001). furthermore, the vldl plasma level did not reveal a significant difference between endurance and the acute exercises. 4. discussion based on the findings, there was no difference between the training groups, rev and control groups regarding the level of cho and hdl. however, both endurance exercise and acute exercise trainings resulted in an increase in tg and vldl levels and decrease in ldl level in comparison with the control group. a growing body of evidence has shown that regular exercise with moderate intensity prevents cardiovascular disease due to increased hdl level in the blood. regular exercise boosts the antioxidant system and prevents cardiovascular disease in the long run. santin et al. reported that levels of cho and ldl decreased in rats with mild exercise, but no change was found in levels of hdl and tg (19). rev exerts many effects, such as antioxidant activity, regulation of lipid and lipoprotein metabolism, inhibition of platelet aggregation, and vasodilation (20, 21). rev, as the activator of the enzyme ampk, plays a role in regulating lipid metabolism and prevents the accumulation of lipid in the cells, where it has been revealed that a synthesized derivative of rev was capable of enhancing ampk phosphorylation, and reducing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. vafaee et al. 4 table 1: changes in plasma levels of cholesterol (cho), triglyceride (tg), high density lipoprotein (hdl), low density lipoprotein (ldl) and very low density lipoprotein (vldl) after endurance exercise group cho p tg p hdl p ldl p vldl p c 51.61(38.35) 65(22.07) 33.5(1.64) 33.66(6.88) 13(4.41) vs. 0.96 <0.001 0.42 0.007 <0.001 t 56.37(9.5) 119.12(23.48) 36.5(2.44) 19.62(6.67) 23.82(4.69) c 51.61(38.35) 65(22.07) 33.5(1.64) 33.66(6.88) 13(4.41) vs. 0.94 0.66 0.2 0.74 0.66 s 57.71(6.62) 76.85(15.42) 37.57(5.06) 29.57(7.2) 15.37(3.08) c 51.61(38.35) 65(22.07) 33.5(1.64) 33.66(6.88) 13(4.41) vs. 0.97 0.004 0.1 0.01 0.005 t+s 55.85(10.62) 104.57(10.34) 38.28(4.07) 20.28(8.11) 20.9(2.08) t 56.37(9.5) 119.12(23.48) 36.5(2.44) 19.62(6.67) 23.82(4.69) vs. 0.99 0.001 0.93 0.06 0.001 s 57.71(6.62) 76.85(15.42) 37.57(5.06) 29.57(7.2) 15.37(3.08) t 56.37(9.5) 119.12(23.48) 36.5(2.44) 19.62(6.67) 23.82(4.69) vs. 1.0 0.45 0.77 0.99 0.44 t+s 55.85(10.62) 104.57(10.34) 38.28(4.07) 20.28(8.11) 20.9(2.08) s 57.71(6.62) 76.85(15.42) 37.57(5.06) 29.57(7.2) 15.37(3.08) vs. 0.99 0.04 0.98 0.1 0.04 t+s 55.85(10.62) 104.57(10.34) 38.28(4.07) 20.28(8.11) 20.9(2.08) c = control group, t = train or exercise group, s = supplement or resveratrol, t+s = exercise + resveratrol. table 2: changes in plasma levels of cholesterol (cho), triglyceride (tg), high density lipoprotein (hdl), low density lipoprotein (ldl) and very low density lipoprotein (vldl) after acute exercise group cho p tg p hdl p ldl p vldl p c 40.71(8.51) 67.57(14.5) 35.14(3.71) 34.71(10.78) 13.51(2.9) vs. 0.32 <0.001 0.85 0.04 <0.001 t 52(12.4) 148.25(7.41) 37.5(3.87) 15.5(7.54) 29.65(1.48) c 40.71(8.51) 67.57(14.5) 35.14(3.71) 34.71(10.78) 13.51(2.9) vs. 0.08 0.68 0.53 0.67 0.68 s 54.25(12.2) 76.37(18.85) 38.5(5.04) 28.25(14.12) 15.25(3.72) c 40.71(8.51) 67.57(14.5) 35.14(3.71) 34.71(10.78) 13.51(2.9) vs. 0.57 0.002 0.7 0.28 0.002 t+s 48.16(7.8) 102.83(14.64) 38(5.83) 23.5(7.25) 20.56(2.92) t 52(12.4) 148.25(7.41) 37.5(3.87) 15.5(7.54) 29.65(1.48) vs. 0.98 <0.001 0.98 0.25 0.001 s 54.25(12.2) 76.37(18.85) 38.5(5.04) 28.25(14.12) 15.25(3.72) t 52(12.4) 148.25(7.41) 37.5(3.87) 15.5(7.54) 29.65(1.48) vs. 0.93 0.001 0.99 0.67 0.001 t+s 48.16(7.8) 102.83(14.64) 38(5.83) 23.5(7.25) 20.56(2.92) s 54.25(12.2) 76.37(18.85) 38.5(5.04) 28.25(14.12) 15.25(3.72) vs. 0.7 0.02 0.99 0.85 0.02 t+s 48.16(7.8) 102.83(14.64) 38(5.83) 23.5(7.25) 20.56(2.92) c = control group, t = train or exercise group, s = supplement or resveratrol, t+s = exercise + resveratrol. hepatic tg accumulation, showing a significant therapeutic effect on fatty liver disease (22). in the study by kitada et al., oral administration of risoratrol to diabetic mouse models improved their lipid profiles (23). in other words, the aforementioned study indicated that rev could be an effective supplement for improving renal injury and was capable of increasing mitochondrial biogenesis with mn-sod dysfunction in diabetic mouse models by improving oxidative stress, as well as normalization of the mn-sod function and glucose-lipid metabolism, suggesting an anti-oxidative activity for rev by affecting ampk/sirt1-independent pathway(23). castro et al. found that rev could play a significant role in preventing ldl deposition in the aortic artery endothelium and accelerating its recovery, showing a preventive effect in development of atherosclerotic lesions (24). the findings of the present study are consistent with the findings of kitada et al. (23) and zhu et al. (25), in which this combination was involved in improving lipid profiles. our results this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e16 also exhibited a significant decrease in tg and vldl levels in the exercise group+rev compared to the training group. however, some believe that improvement of coronary heart diseases by rev is not due to its antioxidant property against lipids and changing lipoprotein profile (26). zhu et al. also demonstrated both antioxidant and anti-hyper-lipidemic effects for rev. they showed that administration of rev in hyperlipidemia rats has a significant effect on lipid profiles and plays a role in decreasing lipid profile (tg and cho levels) by decreasing hepatic thiobarbituric acid reactive substances via inhibition of the oxidation of ldl (25). on the other hand, tome-carneiro et al. reported that a grape extract supplement containing rev led to a decrease in the level of oxidized ldl and apolipoprotein-b in patients at high risk of a cardiovascular disease. this supplement was capable of decreasing atherogenic markers and was involved in cardioprotection (21). however, in the current study, the supplementation of rev did not change the level of ldl. this finding is incompatible with tome-carneiro et al. (21). overall, since rev reduces the level of tg, it seems that rev may show a protective effect against lipid peroxidation in athletes by improving the lipid profile and reducing peroxidation of lipids. however, these effects can be affected by several other factors such as type and duration of exercise, the type of model examined, the amount and timing of resveratrol supplementation and other factors. therefore, further studies are required to clarify the effect of this supplement on lipid profiles during endurance and acute exercise. 5. conclusion based on the findings, there was no difference in the level of cho and hdl between the training groups, rev and control groups. however, both endurance exercise and acute exercise trainings resulted in an increase in tg and vldl levels and decrease in ldl level, compared with the control group. 6. appendix 6.1. acknowledgements not applicable. 6.2. authors’ contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids reza vafaee: 0000-0003-0677-4755 hamid soori: 0000-0002-3775-1831 mehdi hedayati: 0000-0001-5816-775x hamid reza hatamabadi: 0000-0002-9085-8806 6.3. funding/support this study was supported technically and financially by shahid beheshti university of medical sciences. 6.4. conflict of interest the authors declare they have no conflict of interest. references 1. finegold ja, asaria p, francis dp. mortality from ischaemic heart disease by country, region, and age: statistics from world health organisation and united nations. international journal of cardiology. 2013;168(2):934-45. 2. mcgill jr hc, mcmahan ca, gidding ss. preventing heart disease in the 21st century: implications of the pathobiological determinants of atherosclerosis in youth (pday) study. circulation. 2008;117(9):1216-27. 3. miyazaki h, oh-ishi s, ookawara t, kizaki t, toshinai k, ha s, et al. strenuous endurance training in humans 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1997;27(6):557-62. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e5 https://doi.org/10.22037/aaem.v9i1.923 ca s e re p o rt possible vertical transmission of covid-19 to the newborn; a case report yekta parsa1,2, nazila shokri1,2, tayebeh jahedbozorgan1,3, zahra naeiji1,3, shahrzad zadehmodares1,3, atefeh moridi1,3∗ 1. department of obstetrics and gynecology, mahdiyeh hospital, shahid beheshti university of medical sciences, tehran, iran. 2. department of obstetrics and gynecology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. preventative gynecology research center, shahid beheshti university of medical sciences, tehran, iran. received: september 2020; accepted: october 2020; published online: 14 november 2020 abstract: vertical transmission of the novel coronavirus 2019 (covid-19), has been reported in case reports and series, while the data regarding its transmission is still not enough. thus, presenting different experiences form various regions could help better understand the virus behavior in pregnancy. we herein report a possible vertical transmission of covid-19 from a mother to the neonate. a 41-year-old mother with signs and symptoms of acute respiratory illness presented with labor pain and vaginal leak at 37 weeks of gestation. she tested positive for covid-19 using rt-pcr and underwent emergency cesarean section delivery and gave birth to a girl neonate. the baby tested positive for the covid-19. although vertical transmission of covid-19 has not been proved yet, but there are several lines of evidences suggesting it. paying close attention to the mother and newborn with covid-19 and long-term follow-up are needed for better understanding of the virus in pregnancy. keywords: severe acute respiratory syndrome coronavirus 2; covid-19; infant, newborn; infectious disease transmission, vertical cite this article as: parsa y, shokri n, jahedbozorgan t, naeiji z, zadehmodares sh, moridi a. possible vertical transmission of covid-19 to the newborn; a case report. arch acad emerg med. 2021; 9(1): e5. 1. introduction the novel coronavirus 2019 (covid-19) has infected more than 4 million people and caused more than 300,000 deaths worldwide by may 2020. it has been declared as pandemic by the world health organization (who) in march 2020 (1). covid-19 pneumonia is highly infectious and can be transmitted through various routes including respiratory droplets and close contact (2). infection during pregnancy has been the spotlight of many studies; yet, evidence on vertical transmission is scarce and mostly based on small series and case reports (3-5). covid-19 infection during pregnancy raises 3 major concerns: first, the treatment and management of pregnant women infected with the virus is still a matter of debate and needs further investigation; second, prenatal and ∗corresponding author: atefeh moridi; department of obstetrics and gynecology, mahdiyeh hospital, shishe gar khaneh alley, fadaian islam avenue, shoosh square, tehran, iran. p. o. box:1185817311, tel: (+98)215506-2628, fax: (+98)215506-2627, emails: a.moridi@sbmu.ac.ir, moridi59@gmail.com, orcid: 4439-7791-0002-0000. pregnancy complications are still unknown and it is not wellestablished whether prenatal covid-19 infection increases the risk of adverse pregnancy outcomes or not; and third, vertical transmission of the virus from the mother to the child needs further investigation. recently, a systematic review evaluated all the published articles on pregnant women infected with covid-19 and reported that vertical transmission of covid-19 does not occur based on the evidence provided so far (3). however, a growing body of evidence suggests the vertical transmission of covid-19 from the mother to the child (4-9). laboratory analysis revealed that amniotic fluid and cord blood from neonates delivered by covid-19 positive mothers were negative for the virus (8, 10). thus, the knowledge regarding vertical transmission of covid-19 is insufficient and adding experience from different regions can help complete the whole picture and understand the behavior of the virus in pregnancy. we herein report a case of vertical transmission of covid-19 to the newborn, confirmed by laboratory analysis and investigation in iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem y. parsa et al. 2 2. case presentation in our center in tehran, iran (mahdiyeh hospital affiliated with shahid beheshti university of medical sciences), from march 1s t to april 20t h , we screened 25 pregnant women with suspected covid-19 infection, 9 of whom tested positive using real time polymerase chain reaction (rt-pcr), which found specimens in nasopharyngeal swab of the patients. the neonates born to 8 of these mothers tested negative for covid-19; however, 1 newborn tested positive 24 hours after birth. the mother of this neonate was a 41-yearold woman, living in tehran, iran, with low socioeconomic background and opium addiction. the pregnancy history included gravid 6, parity 4, live 4, and abortion 1. she had the signs and symptoms of acute respiratory illness including shortness of breath and cough. she underwent spiral chest ct-scan which revealed ground-glass opacities in bilateral upper and lower lobes. the laboratory results revealed lymphopenia (9.2×103 /µl) and elevated c-reactive protein levels (18.8 mg/l). thus, rt-pcr was done for the mother and the result was positive and she was diagnosed with covid19 pneumonia. she presented with labor pain and amniotic fluid leakage and due to previous history of cesarean delivery (4 previous sections), an emergency cesarean delivery was scheduled. the cesarean section was performed with complete protection of the mother, newborn, and the medical team. the result of the delivery was a girl neonate, with 1-min apgar score of 9 and 5-min apgar score of 10, and weigh of 3500 gr. the rt-pcr results of the amniotic fluid and neonate (less than 24 hours after birth) were positive for covid-19 and she was diagnosed with the viral infection. her chest radiography was normal, and the laboratory results were unremarkable. she was vomiting during the first 24 hours after birth, which was due to opium withdrawal syndrome. she was admitted to the neonatal intensive care unit (nicu) and received supportive care without need for respiratory support. the baby was fed formula as the mother was admitted to the icu and isolation for supportive care. after 11 days, she tested negative for covid-19 and the test results at day 14 were also negative. the neonate did not have any symptoms including vomiting, dyspnea, or cough but developed fever (38.6◦c) from the 10t h day of birth. conservative therapy was not successful and thus, a lumbar puncture was performed on day 10, which was clear. the fever resolved with appropriate anti-pyretic therapy and antibiotic therapy. the chest radiography was also unremarkable. she was discharged from the hospital with good condition on day 28. the mother also received supportive care in an isolated unit. she was completely symptom free and afebrile. she was discharged in good condition. 3. discussion the vertical transmission of covid-19 is a matter of debate and the clinical evidence is extremely scanty. in the current study, we reported the possible vertical transmission of covid-19 from a mother to a newborn less than 24 hours after birth. in our report, the newborn girl tested positive in the first 24 hours of her life after a cesarean delivery. although we do not have the rt-pcr results of the placenta, but we believe that the transmission has been vertical as the neonate and amniotic fluid tested positive for the virus less than 24 hours after birth. the current case can contribute to the literature regarding the knowledge of covid-19 in pregnancy. recently, wang et al. (5) reported a neonate with positive rtpcr after 36 hours of birth from a 34-year-old woman who was diagnosed with covid-19. the presented case provides the possibility of vertical transmission of covid-19, while the probability could not been confirmed with laboratory analysis (5). in another recent study of a neonate delivered by cesarean section from an infected mother, there were elevated igm antibody levels and abnormal test results for il-6 and il-10 cytokines 2 hours after birth. the increase in igm antibody level implies that the neonate was infected in utero, as igm antibody usually does not appear until 3 to 7 days after infection and cannot be transmitted through the placenta (6). alzamora et al. (11) also reported a 41-year-old woman undergoing cesarean delivery and the neonate tested positive for covid-19, 16 hours after delivery. igm and igg were positive for the mother on the fourth day after giving birth (9 days after the onset of symptoms). the positive rt-pcr test result on the first day of life indicated the possibility of vertical transmission, which is similar to our study (11). in a recent review, lamouroux et al. (12) reviewed the literature and included the data on 68 deliveries and 71 neonates with maternal infection in the third trimester of pregnancy. only 4 cases were tested positive within 48 hours of birth and they provided several evidence for and against vertical transmission (12). in a systematic review by della gatta et al. (3), which included 51 pregnant women with positive test results for covid-19, they concluded that the high rate of preterm delivery by cesarean delivery was a reason for concern. however vertical transmission was completely rejected by the results of this review (3). karimi-zarchi et al. (7) reviewed data of published articles or official websites up to march 4, 2020, to investigate the the risk of vertical transmission of covid19 to the fetus of infected mothers. they finally included 31 pregnant women with positive covid-19 test results. they reported 2 maternal mortalities, however, there was no evidence for intrauterine transmission of covid-19 from infected pregnant women to their fetuses. chen et al. (8) described the clinical characteristics of 9 pregnant patients with this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e5 covid-19 infection during the third trimester and demonstrated that there is no evidence for intrauterine transmission of covid-19; the results were further confirmed by another systematic review (13). in conclusion, vertical transmission of covid-19 through placenta is still unclear and the existing data in this regard is very limited. however, the current case and similar previous reports support the probability of the virus causing covid19 being transmitted vertically through the placenta. this is supported by the fact that test results of the neonates become positive within the first day of life. the longand short-term effects of covid-19 infection on the neonates are still unclear and should be investigated in follow-ups. the knowledge on vertical transmission of covid-19 is insufficient and adding experience from different regions can help complete the whole picture and understand the nature of the virus in pregnancy. 4. conclusion the fact that the neonate in our case report tested positive for covid-19 within the first day of her life adds to the body of evidence suggesting the possibility of vertical transmission of this disease. 5. declarations 5.1. acknowledgements we would like to thank the patient and her family who participated in this study. we would also like to acknowledge the editorial assistance of diba negar research institute. 5.2. authors’ contributions all authors met the criteria for gaining authorship based on the recommendations of the international committee of medical journal editors. 5.3. conflict of interest there isn’t any conflict of interest to be declared regarding the manuscript. 5.4. ethical issues this study was carried out according to the declaration of helsinki. also, written informed consent for publication of the manuscript and the related individual data were obtained from the patient (ethics code: ir.sbmu.msp.rec.1399.460 ). references 1. sun j, he wt, wang l, lai a, ji x, zhai x, et al. covid19: epidemiology, evolution, and cross-disciplinary perspectives. trends mol med. 2020;26(5):483-95. 2. kucharski aj, russell tw, diamond c, liu y, edmunds j, funk s, et al. early dynamics of transmission and control of covid-19: a mathematical modelling study. lancet infect dis. 2020;20(5):553-8. 3. della gatta an, rizzo r, pilu g, simonazzi g. coronavirus disease 2019 during pregnancy: a systematic review of reported cases. am j obstet gynecol. 2020. 4. fan c, lei d, fang c, li c, wang m, liu y, et al. perinatal transmission of covid-19 associated sars-cov-2: should we worry? clin infect dis. 2020. 5. wang s, guo l, chen l, liu w, cao y, zhang j, et al. a case report of neonatal covid-19 infection in china. clin infect dis. 2020. 6. dong l, tian j, he s, zhu c, wang j, liu c, et al. possible vertical transmission of sars-cov-2 from an infected mother to her newborn. jama. 2020;323(18):1846-8. 7. karimi-zarchi m, neamatzadeh h, dastgheib sa, abbasi h, mirjalili sr, behforouz a, et al. vertical transmission of coronavirus disease 19 (covid-19) from infected pregnant mothers to neonates: a review. fetal pediatr pathol. 2020:1-5. 8. chen h, guo j, wang c, luo f, yu x, zhang w, et al. clinical characteristics and intrauterine vertical transmission potential of covid-19 infection in nine pregnant women: a retrospective review of medical records. lancet. 2020;395(10226):809-15. 9. chen y, peng h, wang l, zhao y, zeng l, gao h, et al. infants born to mothers with a new coronavirus (covid19). front pediatr. 2020;8:104. 10. lu q, shi y. coronavirus disease (covid-19) and neonate: what neonatologist need to know. j med virol. 2020. 11. alzamora mc, paredes t, caceres d, webb cm, valdez lm, la rosa m. severe covid-19 during pregnancy and possible vertical transmission. am j perinatol. 2020. 12. lamouroux a, attie-bitach t, martinovic j, leruez-ville m, ville y. evidence for and against vertical transmission for sars-cov-2 (covid-19). am j obstet gynecol. 2020. 13. cheruiyot i, henry bm, lippi g. is there evidence of intra-uterine vertical transmission potential of covid19 infection in samples tested by quantitative rt-pcr? eur j obstet gynecol reprod biol. 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e45 rev i ew art i c l e antiviral therapy in management of covid-19: a systematic review on current evidence mahmoud yousefifard1, alireza zali2, kosar mohamed ali3, arian madani neishaboori1, afshin zarghi4, mostafa hosseini5,6∗, saeed safari7,8 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. functional neurosurgery research center, shohada tajrish neurosurgical comprehensive center of excellence, shahid beheshti university of medical sciences, tehran, iran. 3. college of medicine, university of sulaimani, sulaimani, iraq. 4. department of medicinal chemistry, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran. 5. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran iran. 6. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 7. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. 8. emergency department, shohadye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: march 2020; accepted: march 2020; published online: 6 april 2020 abstract: background: the purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of covid-19. in addition, clinical trials on the efficacy of antiviral therapies in the management of severe acute respiratory syndrome coronavirus (sars-cov) or middle east respiratory syndrome coronavirus (mers-cov ) have also been reviewed, in order to identify potential treatment options for covid-19. method: an extensive search was performed in medline, embase, scopus, web of science and central databases until the end of march 15, 2020. two independent researchers performed the screening, and finally the related studies were included. results: only one clinical trial on the efficacy of antiviral therapy in management of covid-19 was found. the results depicted that adding lopinavir-ritonavir to the standard treatment regimen of patients with severe covid-19 has no benefits. moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in covid-19, none of which can be used to determine the efficacy of antiviral therapies in confronting covid-19. in addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of sars-cov and mers-cov. conclusion: the current evidence impede researchers from proposing an appropriate antiviral therapy against covid-19, making the current situation a serious concern for international organizations such as world health organization (who). in the time of the current pandemic and future epidemics, organizations such as who should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics. keywords: covid-19; treatment; antiviral therapy cite this article as: yousefifard m, zali a, mohamed ali k, madani neishaboori a, zarghi a, hosseini m, safari s. antiviral therapy in management of covid-19: a systematic review on current evidence. arch acad emerg mede. 2020; 8(1): e45. ∗corresponding author: prof. mostafa hosseini. department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran. email: mhossein110@yahoo.com ; phone: 00982188989125. † corresponding author: dr. saeed safari. department of emergency medicine, shohadye tajrish hospital, tajrish squared, tehran, iran. email: safari266@gmail.com; phone/fax: 00982122721155. 1. introduction in the late 2019, a novel type of coronavirus emerged from wuhan, china, causing patients to show pneumonia-like symptoms (1, 2). later on, the virus spread around the world, and the world health organization announced a covid19 pandemic in march 2020. by march 17, 2020, 190,000 covid-19 cases and approximately 7500 deaths from the virus were identified (3). this large number of infected pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 2 tients in only three months since the first reported case of covid-19 demonstrates that the disease is extremely contagious. covid-19 is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), which belongs to the family coronaviridae. the family that has been responsible for two other viral outbreaks in recent years, the first of which was in 2003 caused by severe acute respiratory syndrome coronavirus (sars-cov ) (4). the second outbreak occurred in 2012 and 2015 due to the spread of middle east respiratory syndrome coronavirus (mers-cov ), another virus from the same family (5, 6). these two epidemics infected many people at the time of their peak, but after the diseases regressed, limited reports of laboratory accidents or animal-to-human transmission were published. until today, no treatments have been reported for covid-19 (7). although some casereports or observational studies have reported a few antiviral drugs being effective in improving the outcome of covid-19 patients (8), no definitive cure has been discovered so far. recently, a chinese research team proposed a treatment protocol for management of covid-19 patients, which included moxifloxacin, levofloxacin (consider tolerance) and arbidol administration (8). however, the underlying evidence for the mentioned treatment protocol is unclear, as there are no clinical trials performed on this matter. several antiviral therapies have been considered to be potentially effective in treating covid-19, including oseltamivir, ganciclovir, arbidol and lopinavir / ritonavir. many clinical trials are currently underway to evaluate the efficacy of different medications on the outcome of covid-19 patients (9), but their results have not been published yet. on the other hand, the quality of these studies is rather unclear. treatments used for sars-cov or mers-cov may be useful in the treatment of covid-19, due to the fact that all of these viruses are from the same family, and they all cause respiratory diseases. nevertheless, a consensus is yet to be reached on this matter. the primary objective of the current systematic review is to evaluate the evidence underlying the efficacy and safety of antiviral therapies in treatment of covid-19 in the current pandemic. another goal for the present study is to investigate the clinical trials performed in recent years on the effects of antiviral therapies on sars-cov or mers-cov to propose potential existing treatments for covid-19. 2. method 2.1. study design the present systematic review was performed in two sections. in the first section, current clinical evidence about the efficacy of antiviral treatments in management of covid-19, namely the covid-19 antiviral therapy section, is presented. the second part provides a review of clinical trials conducted on sars-cov and mers-cov to find proposed antiviral therapies, namely the sars-mers antiviral therapy section. 2.2. selection criteria in the covid-19 antiviral therapy section, all types of performed clinical studies, aiming to evaluate the efficacy and safety of antiviral drugs were included. exclusion criteria comprised in vitro studies, animal studies, guidelines, and review studies. in the sars-mers antiviral therapy section, inclusion criteria consisted of clinical trials on the efficacy and safety of antiviral drugs administered for management of ars-cov and mers-cov. the exclusion criteria in this section contained observational studies, guides, animal studies, and review articles. since sars and mers outbreaks happened in recent years, and there was the opportunity for conduction of clinical trials, only clinical trials were included in this section, as they provide the highest level of evidence. in this section, antiviral therapies for covid-19 are to be suggested, so the provided underlying evidence should be of highest validity. 2.3. search strategy an extensive search was performed on medline (via pubmed), embase, scopus, central, and web of science databases. the keywords were selected using expert opinions, mesh, emtree and related article titles. the keywords in the covid-19 antiviral therapy section were the only keywords associated with covid-19. since a small number of articles were published about the treatment, and the use of antiviral treatments were prevalently not mentioned in the abstracts of the articles, keywords related to "antiviral therapy" were not included in the search. also, the search date was chosen to be from early 2019 until march 15, 2020, since the first report of covid-19 was published in late 2019. the keywords in the sars-mers antiviral therapy section included keywords related to sars-cov and mers-cov in combination with standard filters for clinical trials. similar to the previous section, keywords related to antiviral therapy were not included in the search, due to the limited number of studies. the time range for search was set to be from the inception of the database until march 15, 2020. search strategy in medline is presented in table 1. in addition to the systematic search, an extensive search was also performed on google and google scholar search engines and in the article bibliographies. 2.4. data collection two independent researchers reviewed the titles and abstracts of the records obtained from the databases and selected related articles. next, full texts of these articles were collected and reviewed carefully. finally, related articles suitthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e45 table 1: search queries in medline database section search query covid-19 antiviral therapy coronavirus[tiab] or covid19[tiab] or 2019-ncov[tiab] or covid19 virus[tiab] or covid-19 virus[tiab] or 2019-ncov disease[tiab] or 2019 novel coronavirus disease[tiab] or 2019-ncov infection[tiab] or 2019-ncov[tiab] or coronavirus disease 2019 virus[tiab] or sars-cov-2[tiab] or sars2[tiab] or 2019 novel coronavirus[tiab] or 2019 novel coronavirus infection[tiab] or coronavirus disease 2019[tiab] or coronavirus disease-19[tiab] or new coronavirus[tiab] or wuhan coronavirus[tiab] or wuhan seafood market pneumonia virus[tiab] or "severe acute respiratory syndrome coronavirus 2"[supplementary concept] or "covid-19"[supplementary concept] sars-mers antiviral therapy 1. "coronavirus"[mh] or "betacoronavirus"[mh] or "middle east respiratory syndrome coronavirus"[mh] or "sars virus"[mh] or coronavirus[tiab] or coronaviruses[tiab] or deltacoronavirus[tiab] or deltacoronaviruses[tiab] or munia coronavirus hku13[tiab] or coronavirus hku15[tiab] or coronavirus, rabbit[tiab] or rabbit coronavirus[tiab] or coronaviruses, rabbit[tiab] or rabbit coronaviruses[tiab] or bulbul coronavirus hku11[tiab] or thrush coronavirus hku12[tiab] or betacoronavirus[tiab] or betacoronaviruses[tiab] or tylonycteris bat coronavirus hku4[tiab] or pipistrellus bat coronavirus hku5[tiab] or human coronavirus hku1[tiab] or hcov-hku1[tiab] or rousettus bat coronavirus hku9[tiab] or middle east respiratory syndrome coronavirus[tiab] or mers-cov[tiab] or mers virus[tiab] or mers viruses[tiab] or virus, mers[tiab] or viruses, mers[tiab] or middle east respiratory syndrome-related coronavirus[tiab] or middle east respiratory syndrome related coronavirus[tiab] or sars virus[tiab] or severe acute respiratory syndrome virus[tiab] or sars-related coronavirus[tiab] or coronavirus, sarsrelated[tiab] or sars related coronavirus[tiab] or sars-cov[tiab] or urbani sars-associated coronavirus[tiab] or coronavirus, urbani sars-associated[tiab] or sars-associated coronavirus, urbani[tiab] or urbani sars associated coronavirus[tiab] or sars coronavirus[tiab] or coronavirus, sars[tiab] or severe acute respiratory syndrome-related coronavirus[tiab] or severe acute respiratory syndrome related coronavirus[tiab] or sars-associated coronavirus[tiab] or coronavirus, sars-associated[tiab] or sars associated coronavirus[tiab] 2. (randomized controlled trial [pt] or controlled clinical trial [pt] or randomized [tiab] or placebo [tiab] or drug therapy [sh] or randomly [tiab] or trial [tiab] or groups [tiab]) not (animals [mh] not humans [mh]) 3. #1 and #2 able based on inclusion and exclusion criteria were included in the present systematic review. then, the two researchers summarized the articles and collected data including the name of the first author, publication year, country in which the study was conducted, type of the study, sample size, age and sex distribution of the patients, the drug used, dose and duration of administration, route of administration and treatment outcome. any disagreements were resolved by a discussion with a third researcher. 3. results 3.1. studies on covid-19 3.1.1 characteristics the initial search yielded 4997 articles. after eliminating duplicates, 2485 records were reviewed, and 22 studies were included in the current systematic review (figure 1) (1031). 20 articles were conducted in china, one article was conducted in south korea and one study was performed in singapore. only one clinical trial was found, which evaluated the efficacy of lopinavir-ritonavir in treating patients with severe covid-19 (10). among the included articles, 16 were case-series (11-13, 15, 16, 19-23, 25-29, 31) and 5 were case-reports (14, 17, 18, 24, 30). the articles studied 2856 covid-19 patients, 1883 (65.9%) of whom were treated with antiviral agents. the most commonly used antivirals were lopinavir / ritonavir, oseltamivir, ribavirin and arbidol, respectively. route and duration of administration were not reported in most of the studies. the most common route of administration among the studies was oral administration, and the duration of administration varied from two to 14 days. all of the studies used other therapies, such as antibiotics, immunoglobin, interferon, glucocorticoids, methylprednisolone, and antiparasitic and antifungal drugs in addition to the antiviral therapy to manage covid-19 patients (table 2). 3.1.2 antiviral therapy for management of covid-19 the only clinical trial found was performed on 199 patients with severe covid-19, using lopinavir-ritonavir regimen. in this randomized open-labeled clinical trial, patients were divided into two groups: lopinavir-ritonavir (99 patients) group and standard treatment group. in addition to lopinavirritonavir (400 mg / 100 mg, twice daily; 14 days), standard treatments such as antibiotics, invasive or non-invasive ventilation and extracorporeal membrane oxygenation (ecmo) and vasopressor were also used. the findings of this study showed that patients receiving lopinavir-ritonavir had a similar recovery process to those receiving standard treatment. 28-day mortality and viral rna load were not significantly different between the two groups (10). the researchers this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 4 table 2: clinical studies that reported anti-viral therapy in management of covid-19 first author; year; country sample size age (year)* male status of patients antiviral agent antiviral treated patients (n) dosage route of administration duration of treatment combination main findings randomized clinical trial cao et al; 2020; china (10) 199 58 (50 to 68) 120 severe covid-19 patients lopinavir/ ritonavir 99 400 mg/100 mg twice daily oral 14 yes lopinavir–ritonavir administration is not superior to standard care in management of adult patients with severe covid-19. clinical improvement and mortality rate are similar in lopinavir–ritonavir treated and standard care groups. case-series chen n; 2020; china (11) 99 21 to 82 67 covid-19 patients oseltamivir 75 75 mg twice a day oral 3 to 14 yes recovery rate: 31%; mortality rate: 11% chen q; 2020; china (12) 9 14 to 56 5 symptomatic covid-19 lopinavir/ ritonavir 9 800 mg/200 mg daily oral 4 to 11 yes no mortality. time from onset of treatment to negative result of cov-test was 4-11 days. length of hospital stay was 9 to 20 days. guan w; 2020; china (13) 1099 47.0 (iqr: 35.0–58.0) 637 non-severe and severe covid-19 patients oseltamivir 393 nr nr nr yes administration of oseltamivir did not decrease icu admission and need for ventilator or death hu z; 2020; china (15) 24 5 to 95 8 asymptomatic covid-19 infection not specified 21 nr nr nr yes no mortality, no icu admission, no severe complication huang c; 2020; china (16) 41 49 (iqr 41.0–58.0) 30 symptomatic covid-19 oseltamivir 38 nr nr nr yes 6 patients died 28 patients were discharged liu k; 2020; china (19) 137 20 to 83 61 severe covid-19 not specified 105 nr nr nr yes 16 patients died during the study. liu l; 2020; china (20) 51 16 to 68 32 discharged covid-19 patients lopinavir/ ritonavir oseltamivir arbidol 51, 7, 2 nr oral nr yes duration of hospital stay was 9-13 days. 1 patient died. qin x; 2020; china (21) 89 23 to 86 45 all covid-19 patients admitted to a center lopinavir/ ritonavir, other anti-viral 84, 5 nr nr nr yes 16 patients were discharged and 1 patient died. shang j; 2020; china (22) 416 49 (iqr: 36-61) 194 survived and dead covid-19 patients not specified 380 nr nr nr yes anti-viral administration did not affect mortality rate (5.6% in non-treated vs. 12.9 treated; p=0.288) wang d; 2020; china (23) 138 22 to 92 75 icu and non-icu admitted covid-19 patients oseltamivir 124 nr nr nr yes 6 patients died and 36 patients were admitted to icu. wu j; 2020; china (25) 80 46.10 ± 15.42 39 all severity ranges of covid-19 ribavirin 80 nr nr 2-12 days yes 21 patients were discharged and 59 patients remained in hospital. xu x; 2020; china (26) 62 41 (iqr: 32-52) 35 symptomatic covid-19 lopinavir/ ritonavir, arbidol, lopinavir/ ritonavir + arbidol 25, 1, 21 lopinavir 400 mg twice daily ritonavir 100 mg twice daily, arbidol 200 mg three time daily nr nr yes one patient was discharged. other patients remained in hospital yang w; 2020; china (27) 149 45.11 ± 13.35 81 all covid-19 patients admitted to a center not specified 140 nr nr nr yes no mortality. 73 patients were discharged and 76 remained in hospital. young be; 2020; singapore (28) 18 31 to 73 9 symptomatic covid-19 lopinavir/ ritonavir 5 nr nr nr yes two patients recovered and the condition of 2 other patients deteriorated. only one patient completed the 12-day planned protocol. four patients experienced side effects of antiviral therapy zhang g; 2020; china (29) 221 20 to 96 108 non-severe and severe confirmed covid-19 patients not specified 196 nr nr nr yes 12 patients died. chest ct improved after administration of ecmo and imv zhou z; 2020; china (31) 10 29 to 68 8 confirmed covid-19 patients lopinavir/ ritonavir, arbidol 8, 3 nr oral nr yes 1 patient died, 5 patients remained hospitalized and 4 patients were discharged case reports han x; 2020; china (14) 1 23 1 diabetic patient with covid-19 oseltamivir/ gancivlovire 1 nr nr 15 yes patient was discharged from hospital after 15 days li w; 2020; china (17) 5 10 months to 6 years 4 children with covid-19 not specified 2 nr nr nr yes the antiviral therapy did not change the outcome or length of stay lim j; 2020; south korea (18) 1 54 1 symptomatic covid-19 patient lopinavir/ ritonavir 1 75 mg twice a day/50 mg twice daily oral 9 yes good recovery. it is not clear that the decreased load of virus is due to the nature of healing process or a result of anti-viral therapy wang z; 2020; china (24) 4 19 to 63 3 covid-19 patients lopinavir/ ritonavir, arbidol, sfjdc 4 400 mg/100 mg twice daily, 0.2 g, three time daily, 2.08 g, three time daily oral 6-16 days antibiotic 2 patients recovered and 2 patients remained in hospital zhang z; 2020; china (30) 2 38 1 symptomatic covid-19 patients oseltamivir and arbidol 2 nr nr nr yes both patients recovered and were discharged * age was reported as range, mean±sd or median (interquartile rang [iqr]). ecmo: extracorporeal membrane oxygenation; imv: invasive mechanical ventilation; nr: not reported; icu: intensive care unit; ct: computed tomography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e45 figure 1: flow diagram of screening process of present systematic review. rct: randomized clinical trial. concluded that lopinavir-ritonavir administration in patients with severe covid-19 was not more effective than the standard treatment. as previously mentioned, all of the other studies were case-reports and case-series. moreover, most of the studies did not provide an analysis regarding the efficacy of antiviral therapy in the treatment course of covid19 patients. for instance, chen et al. reported no deaths among nine patients treated with lopinavir/ritonavir. however, the sample size of the mentioned article was quite small (12). according to the existing statistics, the mortality rate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. yousefifard et al. 6 of covid-19 among patients aged 10 to 60 years, varies between 0.2% and 1.3% (3). hence, for every 100 patients in this age group, only one patient dies. therefore, the sample size was probably not large enough to observe at least one death. in another study, hu et al. studied 24 asymptomatic patients and reported no mortality or icu admission, and no serious complication in 21 patients treated with antiviral agents. nonetheless, in addition to the small sample size, since the patients were asymptomatic, the severity of covid-19 was rather mild in them. therefore, the recovery of the patients might have been due to their mild disease, rather than the efficacy of the antiviral drugs used (15). guan et al. studied 1099 patients, 393 of which were treated with oseltamivir and showed that icu admission, need for mechanical ventilation, or death rate was 9.2% among the oseltamivir-treated group, whilst the rate was 4.4% in the group that was not treated with oseltamivir. in other words, oseltamivir administration was ineffective in decreasing icu admission rate, the need for ventilator and death rate among the patients (13). shang et al. performed a study on 416 patients, indicating that antiviral drugs have no effects on the mortality rate of covid-19 patients. in their study, the mortality rate was 12.9% among the group treated with antiviral drugs, whereas the group which did not receive the antiviral treatment had a mortality rate of 5.6% (22). furthermore, in singapore, young et al. studied 18 patients, and administered lopinavir/ritonavir for only five patients, two of whom recovered and two deteriorated. only one patient tolerated the antiviral regimen and completed the 12-day treatment course. after the start of antiviral treatments, liver test results became abnormal in three of the patients (28). also, li et al. examined five children with covid-19 (two patients treated with antiviral drugs and three patients did not receive antiviral therapy), indicating that antiviral agents did not change the outcome or the duration of hospital stay (17). lim et al. presented a 54-year-old non-smoker woman with no medical history, in whom the viral load started to decline and symptoms started to alleviate gradually with the start of lopinavir/ritonavir treatment, and eventually, the patient was discharged. the researchers reported that it is not clear that the reduced burden of covid19 is due to the healing process or to the administration of anti-viral therapy (18). furthermore, han et al. and zhang et al. reported complete recovery in one patient who had diabetes and was treated with oseltamivir/ganciclovir (14) and two patients treated with oseltamivir and arbidol (30), respectively. there are also studies available that, despite having an acceptable sample size, did not report the final outcome of a large portion of their patients. for instance, wu et al. did not report any deaths among 80 patients treated with ribavirin, while 59 patients were still not discharged and their outcome was still unclear at the time of the submission of the article (25). xu et al. (26), yang et al. (27) and wang et al. (24) also observed no deaths in their studies. however, the majority of the patients they reviewed were still under treatment, with an unclear final outcome, at the time of the publication of their articles. 3.2. studies on sars-cov and mers-cov an extensive search was conducted in databases, in order to find the existing evidence regarding antiviral therapies for treatment of diseases caused by sars-cov and mers-cov, which are in the same family as sars-cov-2. in this section, only clinical trials were supposed to be found. 2004 non-duplicate articles were reviewed, and no clinical trials were performed on the antiviral treatments in managing sars-cov and mers-cov patients (figure 1). only one clinical trial protocol commissioned by a research team in saudi arabia existed. this study, named as the miracle trial, was designed to evaluate the efficacy of lopinavir / ritonavir and interferon-β1b combination therapy in the treatment of mers-cov patients. the study is currently ongoing, and their results have not been published yet (32). therefore, no clinical trials exist on the basis of which an antiviral drug can be suggested for covid-19, not even for sars-cov and mers-cov. 4. discussion the findings of the present study indicated that only one clinical trial was completed on the efficacy and safety of antiviral agents in management of covid-19 patients, which showed ineffectiveness of lopinavir-ritonavir in improving patients’ outcomes. moreover, no clinical trials exist on treatments for sars-cov and mers-cov. furthermore, in 2019 and 2020, 21 case-series and case-reports provided reports about antiviral treatments in management of covid-19 patients, none of which can be taken into account when assessing the clinical usefulness of antiviral treatments against covid-19. in general, no study has examined the efficacy of antiviral therapies alone in treatment of covid-19, and all of the existing articles have used other treatments such as antibiotics, immunoglobulin, interferon, glucocorticoids, antifungal and antiparasitic drugs in their studies. hence, the reports presented cannot be attributed solely to antiviral drugs. therefore, the existing literature regarding the efficacy of antiviral therapy in management of covid-19 patients has serious limitations including: 1. only one clinical trial has been conducted on the matter, depicting that lopinavir-ritonavir is not superior to the standard treatments in management of covid-19 patients. 2. in all of the existing case-series and case-reports, antiviral agents were used in combination with other medications, and therefore the observed outcomes cannot be solely attributed to antiviral therapy. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e45 3. since there was no placebo group in the case-series and case-reports, one cannot determine that the outcomes are due to antiviral therapy or the nature of healing process or both. 4. follow-up was incomplete in some studies, and a great proportion of the patients have unclear outcomes. 5. the sample size was small in most of the studies, and some were even case reports. recently, zhang et al. posted a guideline in the lancet respiratory medicine journal, recommending the administration of arbidol for management of covid-19 patients. however, this guideline has limitations. in general, the underlying evidence for this guideline are unclear. secondly, based on the present systematic review, arbidol was used as the second line of therapy in all of the included studies. hence, the drug appears to be inappropriate for the first line of therapy (8). nevertheless, lopinavir-ritonavir being ineffective in management of covid-19 patients highlights the need to search for other antiviral therapies. many existing guidelines and instructions propose antiviral drugs for management of covid-19 patients, based on the studies performed on sars-cov and mers-cov. therefore, in the current study we aimed to summarize the evidence obtained from clinical trials to determine the level of evidence underlying the mentioned proposal. surprisingly, no completed clinical trial on sars-cov and mers-cov was found, and all of the proposals were based on simulation studies, in vitro studies, pre-clinical studies or at best, observational studies and case-series (33-38). after an epidemic has subsided, researchers are reluctant to perform further investigations on the matter, which is a major pitfall in research and can have several reasons. the first and most important reason is the decline in the number of patients, which severely limits the possibility of performing a clinical trial. secondly, the previous two epidemics, namely sars-cov and mers-cov, never became a pandemic, and the majority of the cases were in a limited geographic region. therefore, after the suppression of the epidemics and decline in the number of patients, the two diseases were eliminated from the list of priorities of international organizations. if those international organizations, such as the world health organization, had further insisted on the importance of the subject and provided grants for independent researches, maybe a few effective antiviral agents for sars-cov and mers-cov would have existed, which could be helpful in management of covid-19, decreasing its burden on societies. a lesson should be learned from the covid-19 pandemic and negligence of health policy makers in setting up clinical trials during sars-cov and mers-cov epidemics, so that in the current pandemic and future epidemics, researches and welldesigned clinical trials are planned-out while the disease is at its peak, the findings of which can be used when necessary. 5. conclusion findings of the current systematic review indicated that it is not clear whether the currently used antiviral agents are beneficial in improving the outcome of covid-19 patients or not. one clinical trial and some case-series suggest that these drugs may not have an impact on the final outcome of covid-19 patients. furthermore, lack of published clinical trials on sars-cov and mers-cov, which were epidemics in recent years, impedes suggesting a potential antiviral treatment for covid-19. the current situation is a serious red flag for international organizations such as the world health organization. in the time of the current pandemic and future epidemics, organizations such as who should pursue more proactive actions and plan well-designed clinical trials to be able to use the results in managing future pandemics. 6. declarations 6.1. acknowledgements none 6.2. authors contributions study design: ss, my, mh data gathering: my, amn, kma interpreting the findings: all authors writing the first draft: my, amn and ss. critically revised the manuscript: all authors authors orcids mahmoud yousefifard: 0000-0001-5181-4985 alireza zali: 0000-0002-2298-2290 kosar mohamed ali: 0000-0001-5533-2924 arian madani neishaboori: 0000-0002-1920-9299 afshin zarghi: 0000-0003-2477-9533 mostafa hosseini: 0000-0002-1334-246x saeed safari: 0000-0002-7407-1739 6.3. funding support this study was supported by shahid beheshti university of medical sciences. 6.4. conflict of interest there is no conflict of interest. 6.5. role of the funding source shahid beheshti university of medical science did not has any role in study design, data collection, analysis, interpretation of data, writing of the report; 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8(1): e79 rev i ew art i c l e accuracy of canadian ct head rule and new orleans criteria for minor head trauma; a systematic review and meta-analysis abeer kadum abass alzuhairy1∗ 1. lecturer in diagnostic imaging surgery department, college of medicine, university of sulimani kurdistan region, iraq. received: august 2020; accepted: september 2020; published online: 8 september 2020 abstract: introduction: the present meta-analysis has two objectives; primarily, the predictive values of canadian computed tomography (ct) head rule (cchr) and new orleans criteria (noc) will be compared. secondly, the possibility of interchangeable use of the two models in cases of contraindication will be evaluated. method: an extensive search was performed in medline, embase, scopus and web of science electronic databases from the inception of databases until the end of july 2020. all prospective and retrospective observational and diagnostic accuracy studies comparing noc and cchr on a single group of patients were included. data were entered to stata 14.0 statistical program, and analyses were performed using "metandi" command. results: data from 14 articles were included (21140 samples). summary sensitivity, specificity, and diagnostic odds ratio of cchr in prediction of positive ct findings were 89.8% (95% ci: 79.6 to 95.2), 38.3% (95% ci: 34.0 to 42.8), and 5.5 (95% ci: 2.3 to 13.1), respectively. in addition, summary sensitivity, specificity, and diagnostic odds ratio of noc in prediction of positive ct findings were 97.2% (95% ci: 89.7 to 99.2), 12.3% (95% ci: 7.4 to 19.8), and 4.8 (95% ci: 1.2 to 18.3), respectively. summary sensitivity, specificity, and diagnostic odds ratio of cchr in prediction of clinically important tbi (citbi) in mild tbi patients were 92.5% (95% ci: 79.5 to 97.5), 40.1% (95% ci: 34.8 to 45.6), and 8.3 (95% ci: 2.4 to 29.2), respectively. in addition, summary sensitivity, specificity, and diagnostic odds ratio of noc in prediction of citbi were 98.3% (95% ci: 93.8 to 99.6), 8.5% (95% ci: 4.8 to 14.5), and 5.4 (95% ci: 1.5 to 20.0), respectively. conclusion: the present meta-analysis demonstrated that both cchr and noc scores have a good predictive value in predicting the presence of abnormal findings in ct scan and citbi. the similar performance of cchr and noc models results in their interchangeable use in cases of contraindication. keywords: sensitivity and specificity; predictive value of tests; craniocerebral trauma; systematic review; meta-analysis cite this article as: alzuhairy a k a. accuracy of canadian ct head rule and new orleans criteria for minor head trauma; a systematic review and meta-analysis. arch acad emerg med. 2020; 8(1): e79. 1. introduction traumatic brain injury (tbi) is one of the most common causes of emergency department referrals worldwide. the global burden of tbi has been increasing in recent years, with an increasing prevalence rate of 8.4% between 1990 and 2016, accompanied by a increasing incidence rate of 3.6% in years of life lived with disability (1). the gold standard in diagnosis of intracranial complications after tbi is computed tomography (ct) scan. however, mild tbi is the most prevalent type of tbi, in which brain ct scans ∗corresponding author: abeer kadum abass alzuhairy;surgery department, college of medicine, university of sulimani kurdistan region, iraq. tel: +9847702213543, email: drabealzuhairy@yahoo.com are usually normal (2). therefore, unnecessary ct scans are quite prevalent. in an attempt to reduce the number of unnecessary ct scans, several scoring systems have been introduced (3-10), including the canadian ct head rule (cchr) and the new orleans criteria (noc) (11, 12). the performance of these two models has been validated in various studies (13-16), but limitations have been attributed to each of these scoring systems. for instance, noc is only applicable in patients with a glasgow coma scale (gcs) of 15, and cannot be used for patients with a gcs of 14 or 13. on the other hand, cchr cannot be applied to patients under 18 years of age, patients on blood thinners and patients having seizures after a head trauma. these limitations have caused an uncertainty regarding which of the two scoring systems has better performance in identifying high-risk patients, and whether these tools can be used interchangeably. to evaluate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. kadum abass alzuhairy 2 the performance of a rule out criteria in identifying high risk patients in mild tbi, two major outcomes will be assessed, including positive ct scan findings and clinically important tbi (citbi). existing studies have attempted to evaluate the diagnostic value of these two decision rules in predicting positive ct findings and citbi to reduce unnecessary ct scans (13, 1720). however, a consensus over the subject is yet to be achieved. hence, the present meta-analysis has two objectives; primarily, the predictive values of cchr and noc will be compared; and secondly, the possibility of interchangeable use of the two models in cases of contraindication will be evaluated. 2. method 2.1. search strategy to achieve the objectives of the present study, an extensive search was performed in medline, (via pubmed), embase, scopus and web of science electronic databases from the inception of databases until the end of july 2020. in addition, pubmed central records were also added, so that no articles would be missed. initially, keywords related to traumatic brain injury in combination with keywords related to canadian ct head rule or new orleans criteria were used in the search. however, the number of the achieved records was low. hence, to perform a more extensive search, only keywords related to canadian ct head rule or new orleans criteria were used in the search. the search term in medline database is presented below. "canadian computed tomography head rule" [title / abstract] or "canadian ct head rule" [title / abstract] or "new orleans criteria" [title / abstract] in addition to the systematic search, a manual search was also performed via google and google scholar search engines and in related articles’ bibliography to include articles that were not indexed or not found. 2.2. selection criteria all prospective and retrospective observational and diagnostic accuracy studies, performing a comparison between the two models of noc and cchr on a single group of patients, were entered to the present study. exclusion criteria were lack of reporting sensitivity and specificity or true positive, true negative, false positive and false negative. other exclusion criteria were lack of assessment of ct scan findings or citbi, studies performed on children, failure to compare cchr and noc criteria and review studies. 2.3. data extraction and quality assessment two independent researchers screened the titles and abstracts of the retrieved records, based on the inclusion and exclusion criteria. next, potentially relevant studies were screened more carefully, and finally, related articles were included. then, the two researchers independently summarized the included articles into a checklist, composed of data including first author’s name, publication year, country, study design, sampling method, sample size, age, gender distribution, outcome, sensitivity, specificity, true positive, true negative, false positive and false negative. any disagreements were resolved by discussion. furthermore, evaluated outcomes included positive findings on ct and citbi. quality control of the studies was performed based on the quality assessment of diagnostic accuracy studies version 2.0 (quadas-2) (21). 2.4. statistical analysis data were entered to stata 14.0 statistical program, and analyses were performed using "metandi" command. analyses were performed in two separate sections according to the evaluated outcomes. initially, the predictive values of cchr and noc in ct scan positive findings were assessed. next, the predictive values of cchr and noc in citbi were evaluated. to assess publication bias, deek’s funnel plot asymmetry test was used. results are presented as sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio with 95% confidence interval (95% ci). 3. results 3.1. characteristics the search resulted in 406 records. after eliminating duplicates and screening, 64 titles of potentially relevant studies were screened in more detail, and finally data from 14 articles were included in the present meta-analysis (11, 13, 14, 17-19, 22-29) (figure 1). these articles entailed 21140 samples. of these, 1940 patients had a positive ct scan finding and 19180 patients had a negative ct scan. of the 1940 patients with positive ct scan, 594 citbis were observed. the evaluated outcome was only positive ct scan findings in eight articles, only citbi in two studies, and both outcomes in 5 studies. table 1 summarizes the characteristics of the included studies. 3.2. accuracy of cchr and noc in prediction of positive ct findings summary sensitivity, specificity, and diagnostic odds ratio of cchr in prediction of positive ct findings were 89.8% (95% ci: 79.6 to 95.2), 38.3% (95% ci: 34.0 to 42.8), and 5.5 (95% 2.3 to 13.1), respectively. in addition, summary sensitivity, specificity, and diagnostic odds ratio of noc in prediction of positive ct findings were 97.2% (95% ci: 89.7 to 99.2), 12.3% (95% ci: 7.4 to 19.8), and 4.8 (95% ci: 1.2 to 18.3), respectively (table 2 and figure 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e79 3.3. accuracy of cchr and noc in prediction of citbi summary sensitivity, specificity, and diagnostic odds ratio of cchr in prediction of citbi in patients with mild traumatic brain injuries were 92.5% (95% ci: 79.5 to 97.5), 40.1% (95% ci: 34.8 to 45.6), and 8.3 (95% ci: 2.4 to 29.2), respectively. in addition, summary sensitivity, specificity, and diagnostic odds ratio of noc in prediction of citbi were 98.3% (95% ci: 93.8 to 99.6), and 8.5% (95% ci: 4.8 to 14.5), 5.4 (95% ci: 1.5 to 20.0), respectively (table 2 and figure 2). 3.4. quality assessment and risk of bias risk of bias assessment based on quadas-2 scale showed that risk of bias regarding patient selection was high in four studies, and unclear in 2 studies. in addition, flow and timing was high risk in 2 studies and unclear 2 other studies. other items were categorized as low risk in risk of bias assessment and applicability domains (table 3 and figure 3). deeks’ funnel asymmetry plots showed that there was no publication bias in assessment of accuracy of cchr and noc in prediction of positive ct findings (p for cchr = 0.65; p for noc = 0.13) and citbi (p for cchr = 0.84; p for noc = 0.50) (figure 3). 4. discussion the present meta-analysis showed that both cchr and noc scores have good predictive value in predicting abnormal findings in ct scan and citbi. although noc’s sensitivity was slightly higher than that of cchr, but cchr’s specificity was much higher than that of noc. however, in interpreting the results of the two models, bear in mind that both models are designed for screening patients and identifying high risk ones to decrease the number of unnecessary ct scans. in screening tests, sensitivity is more important than specificity, because the task of these tests is to select eligible patients for ct scan. hence, these two models are not designed for a definite diagnosis determination, and a low specificity is not considered a weakness of the tests. accordingly, it can be concluded that the values of both cchr and noc models in screening minor head trauma patients are similar. the similarity of the two models in predicting positive ct findings and citbi is a profound finding in the present study, because both cchr and noc models have limitations that affect their performance. for instance, there is no indication for using noc in patients with a gcs less than 15, while cchr is recommended for patients having a gcs between 13 and 15. on the other hand, patients under the age of 18 years, patients on blood thinners and patients with seizures after head traumas are the exclusion criteria for cchr. as a result, in cases of contraindication, the other score can be used instead. in a similar systematic review in 2017, webster et al. showed that both cchr and noc models have the same sensitivity in predicting citbi, while the specificity of cchr is much higher than that of noc (10). the findings of the current study are also in line with that of webster et al. however, in the present article, more studies were included and at the end, a meta-analysis was performed, unlike in the review by webster et al. the quality control was performed according to quadas-2 instructions, showing an acceptable status regarding most of the included studies in the fields of risk of bias and applicability, so the results of the present meta-analysis are authentic. on the other hand, no publication bias was observed in the present study, confirming the validity of the findings of our study. the current study demonstrated that the values of cchr and noc models in predicting positive ct findings and citbi are desirable. however, in addition to the diagnostic value, cost-effectiveness is also important. for this purpose, a meta-analysis evaluating 24 economic studies showed that cchr is an economically attractive tool in management of mild tbi (30). nevertheless, there existed limitations in the present study. one of these limitations was the lack of real-time score assessments in most of the included studies. the studies were designed in a way that in most of them, risk factors for intracranial complications used in the cchr and noc were collected and then their performance was evaluated. while, it was more desirable if the physician or the technician would have determined and recorded the decision whether to perform a ct scan based on the two criteria of noc and cchr, using a decision tree, and eventually compared the ct findings with their decision. hence, it is recommended that in future studies, real-time value of both models in predicting positive ct findings and citbi be compared. 5. conclusion the present meta-analysis demonstrated that both cchr and noc scores have a good predictive value in predicting the presence of abnormal findings in ct scan and citbi. the similar performance of cchr and noc models results in their interchangeable use in cases of contraindication. 6. declarations 6.1. acknowledgements i would like to thank dr. mohammed im gubari for his valuable helps in screening process of the paper. 6.2. authors contributions abeer kadum abass alzuhairy contributed to all parts of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. kadum abass alzuhairy 4 authors orcids abeer kadum abass alzuhairy: 0000-0002-2131-4717 6.3. funding support none. 6.4. conflict of interest there is no conflict of interest. references 1. badhiwala jh, wilson jr, fehlings mg. global burden of traumatic brain and spinal cord injury. the lancet neurology. 2019;18(1):24-5. 2. silverberg nd, duhaime a-c, iaccarino ma. mild traumatic brain injury in 2019-2020. jama. 2020;323(2):1778. 3. nakhjavan-shahraki b, yousefifard m, hajighanbari m, oraii a, safari s, hosseini m. pediatric emergency care applied research network (pecarn) prediction rules in identifying high risk children with mild traumatic brain injury. european journal of trauma and emergency surgery. 2017;43(6):755-62. 4. ahmadi s, yousefifard m. accuracy of 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academic emergency medicine. 2012;19(1):2-10. 27. ro ys, shin sd, holmes jf, song kj, park jo, cho js, et al. comparison of clinical performance of cranial computed tomography rules in patients with minor head injury: a multicenter prospective study. academic emergency medicine : official journal of the society for academic emergency medicine. 2011;18(6):597-604. 28. stein sc, fabbri a, servadei f, glick ha. a critical comparison of clinical decision instruments for computed tomographic scanning in mild closed traumatic brain injury in adolescents and adults. annals of emergency medicine. 2009;53(2):180-8. 29. yang xf, meng yy, wen l, wang h. criteria for performing cranial computed tomography for chinese patients with mild traumatic brain injury: canadian computed tomography head rule or new orleans criteria? the journal of craniofacial surgery. 2017;28(6):1594-7. 30. alali as, burton k, fowler ra, naimark dmj, scales dc, mainprize tg, et al. economic evaluations in the diagnosis and management of traumatic brain injury: a systematic review and analysis of quality. value in health. 2015;18(5):721-34. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. kadum abass alzuhairy 6 table 1: characteristics of the included studies author; year; country design) sampling method total sample total age male number outcome chobdari; 2018; iran prospective observational convenience 264 >14 211 positive ct foks; 2018; netherlands prospective observational consecutive 4557 16 to 101 2656 positive ct; citbi jones; 2020; usa prospective observational consecutive 679 ≥16 420 positive ct kavalci; 2014; turkey prospective observational nr 175 ≥18 106 positive ct korley; 2013; usa prospective observational convenience 130 ≥14 63 positive ct lo; 2016; hong kong retrospective observational consecutive 383 all ages nr positive ct mata-mbemba; 2016; japan prospective observational consecutive 142 17 to 88 96 citbi papa; 2012; usa prospective observational consecutive 314 18 to 89 201 positive ct; citbi ro; 2011; korea prospective observational consecutive 696 46.1+18.9 447 positive ct; citbi smith; 2005; netherlands prospective observational consecutive 3181 16 to 102 2244 positive ct; citbi stein; 2009; usa prospective observational consecutive 7955 >10 4415 positive ct stiell; 2005; canada prospective observational consecutive 1822 16 to 99 1246 citbi valle alonso; 2016; spain prospective observational nr 217 16 to 102 135 positive ct yang; 2017; china retrospective observational consecutive 625 >18 339 positive ct citbi: clinically important traumatic brain injuries; ct: computed tomography; nr: not reported. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e79 table 2: prognostic performance of canadian computed tomography head rule and new orleans criteria according to outcome positive ct citbi value 95% ci value 95% ci canadian computed tomography head rule true positive 1554 — 524 — true negative 7576 — 4300 — false positive 9782 — 5818 — false negative 244 — 70 — sensitivity 89.8 79.6 95.2 92.5 79.5 97.5 specificity 38.3 34.1 42.8 40.1 34.8 45.6 positive likelihood ratio 1.5 1.3 1.6 1.5 1.3 1.8 negative likelihood ratio 0.3 0.1 0.6 0.2 0.1 0.6 diagnostic odds ratio 5.5 2.3 13.1 8.3 2.4 29.2 new orleans criteria true positive 1643 — 562 — true negative 3278 — 664 — false positive 14109 — 9436 — false negative 134 — 14 — sensitivity 97.2 89.7 99.3 98.3 93.8 99.6 specificity 12.3 7.4 19.8 8.5 4.8 14.5 positive likelihood ratio 1.1 1.0 1.2 1.1 1.0 1.1 negative likelihood ratio 0.2 0.1 0.8 0.2 0.1 0.7 diagnostic odds ratio 4.8 1.3 18.3 5.4 1.5 20.0 ci: confidence interval; citbi: clinically important traumatic brain injuries; ct: computed tomography. table 3: risk of bias assessment of included studies author; year risk of bias applicability patients selection index test reference test flow and timing patients selection index test reference test chobdari; 2018 high low low high low low low foks; 2018 low low low low low low low jones; 2020 low low low low low low low kavalci; 2014 unclear low low low low low low korley; 2013 high low low high low low low lo; 2016 high low low unclear low low low mata-mbemba; 2016 low low low low low low low papa; 2012 low low low low low low low ro; 2011 low low low low low low low smith; 2005 low low low low low low low stein; 2009 low low low low low low low stiell; 2005 low low low low low low low valle alonso; 2016 unclear low low low low low low yang; 2017 high low low unclear low low low low: low risk; high: high risk; unclear: unclear risk of bias. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. kadum abass alzuhairy 8 figure 1: prisma flow diagram of the present meta-analysis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e79 figure 2: hierarchical summary receiver-operating characteristic (hsroc) curves of canadian computed tomography head rule and new orleans criteria in prediction of computed tomography findings and clinically important traumatic brain injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. kadum abass alzuhairy 10 figure 3: risk of bias assessment and publication bias in canadian computed tomography head rule and new orleans criteria according to outcome. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion conclusion declarations references emergency. 2018; 6 (1): e3 ca s e re p o rt using intra-aortic balloon pump for management of cardiogenic shock following aluminum phosphide poisoning; report of 3 cases ahmad bagheri-moghaddam1, hasan abbaspour1, shahrad tajoddini2, vahideh mohammadzadeh3, ali moinipour4, bita dadpour5∗ 1. department of anesthesiology, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. neuroscience research center, institute of neuropharmacology, kerman university of medical sciences, kerman, iran. 3. school of pharmacy, mashhad university of medical sciences, mashhad, iran. 4. department of cardiac surgery, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 5. medical toxicology research center, school of medicine, mashhad university of medical sciences, mashhad, iran. received: october 2017; accepted: november 2017; published online: 12 january 2018 abstract: introduction: aluminium phosphide (alp) poisoning mortality rate has been reported as high as 70-100%, and refractory hypotension and cardiogenic shock are the two most common presentations leading to death. due to lack of specific antidote, all treatments are focused on supportive care and recently, intra-aortic balloon pump (iabp) has been suggested to treat cardiogenic shock resulting from toxic myocarditis. in the current paper, we introduce three alp poisoned patients for whom iabp was applied to manage their refractory shock. case presentation: two men and one woman who were admitted to emergency department (ed) of imam reza academic hospital, mashhad, iran due to intentional alp poisoning are reported. the cases visited the ed shortly after ingestion and nearly all of them showed hypotension, tachycardia and metabolic acidosis during early hospitalization. due to persistent shock state, despite receiving intravenous fluid therapy and vasopressor agents, iabp insertion was performed in these cases. finally, one of them survived and the other two died. conclusion: it still cannot be decided whether iabp insertion is effective in cases of alp poisoning or not. it might be reasonable to try this intervention along with other conservative treatments in patients who survive more than 12 hours and consistently suffer from refractory hypotension. keywords: poisoning; shock, cardiogenic; intra-aortic balloon pumping; patient outcome assessment © copyright (2018) shahid beheshti university of medical sciences cite this article as: bagheri-moghaddam a, abbaspour h, tajoddini sh, mohammadzadeh v, moinipour a, dadpour b. using intra-aortic balloon pump for management of cardiogenic shock following aluminum phosphide poisoning; report of 3 cases. emergency. 2018; 6 (1): e3. 1. introduction aluminium phosphide (alp), the main component of “rice tablet”, is frequently used as a rodenticide, fumigant and pesticide (1-5). it is easily available in some countries such as iran and india, and as a result many cases of suicide attempts have been reported with alp in these countries (5, 6). the exact mechanism of toxicity is not clear, but release ∗corresponding author: bita dadpour; medical toxicology research center, school of medicine, mashhad university of medical sciences, mashhad, iran. email: dadpourb@mums.ac.ir of phosphine gas and subsequent cellular events including cytochrome oxidase inhibition and oxidative stress are proposed as the possible mechanism (7, 8). mortality rate of alp poisoning has been reported as high as 70-100%, and refractory hypotension and cardiogenic shock are the two most common presentations leading to death (9, 10). due to lack of specific antidote, all treatments are focused on supportive care and researches are still in progress to make advancements in alp poisoning management (11-15). recently, intra-aortic balloon pump (iabp) has been suggested to treat cardiogenic shock resulting from toxic myocarditis following various poisonings (16, 17). there are some reports of iabp this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. bagheri-moghaddam et al. 2 insertion regarding alp poisoning, some successful and some not (18, 19). in the current paper, we introduce three alp poisoned patients for whom iabp was applied to manage their refractory shock. 2. case presentation: 2.1. case 1 a 20-year-old man who ingested alp (5 grams of 56% powder) was admitted to ed with nausea, vomiting, diarrhea and abdominal pain. he was confused on admission. vital signs were as follows: blood pressure (bp) =75/45 mmhg; respiratory rate (rr) = 35/minute; pulse rate (pr) = 100/minute; and oxygen saturation (spo2) = 93% (in room air). intravenous (iv ) fluid therapy by normal saline 0.9% in addition to dopamine infusion was initiated. six hours later, bp and spo2 had dropped to 70/pulse and 90%, respectively, and pr had increased to 110/minute. arterial blood gas (abg) assessment revealed ph=6.9 and hco3=8 meq/l. four vials of sodium bicarbonate were infused. twelve hours later, he was admitted to intensive care unit (icu) due to persistent hypotension and hypoxemia, as well as ventricular systoles, atrial fibrillation (af) and left bundle branch block (lbbb) in electrocardiogram (ecg). on admission to icu, vital signs were pr=120/minute, bp=79/45 mmhg and spo2=88%. fourteen hours after ingestion, he was intubated because of persistent shock state despite iv fluid therapy and administration of norepinephrine 20 micrograms/minute in addition to dopamine 5 to 15 microgram/kg/min. thereafter, 0.5 mg digoxin was injected due to af rhythm and low bp. dilation of left ventricle and ejection fraction (ef) less than 25% was reported in echocardiography. iabp was inserted 18 hours after ingestion and after 97 hours on the 5th day of admission, it was removed as bp and ef had improved. in echocardiography, which was performed on the 9th day, ef was normal, but pulmonary arterial pressure (pap) was 75 mmhg and right ventricle was dilated, and following cardiologist consultation, sildenafil and milrinone were initiated. echocardiography revealed normal values on day 14. he was discharged with normal vital signs and laboratory test results. 2.2. case 2 a 30-year-old woman was admitted to ed 2 hours after ingestion of half an alp tablet. vital signs on admission included: bp=95/70 mmhg, rr=14/minute, pr=77/minute, and spo2=97% (in room air). she was admitted to icu 6 hours later due to refractory hypotension despite administration of iv fluid therapy and vasopressor agents. on admission to icu pulse rate was 114/minute and sbp/dbp was 80/50 mmhg. abg revealed: spo2=93%, ph=7.28, pco2=16.5, hco3=7.8 meq/l and scvo2=45%. she received iv fluid therapy, norepinephrine and dopamine, digoxin 0.5 mg, nac (9 grams within 1 hour, 3 grams within 4 hours and 4 grams within 16 hours), vitamin c 1 gram/day, calcium gluconate 1 gram every 8 hours. finding of echocardiography was lvef=30 -35%. she was intubated 12 hours after ingestion due to respiratory distress and spo2 less than 88% despite oxygen therapy by reserve bag. iabp was inserted 11 hours later. after 24 hours, she developed ventricular arrhythmia and amiodarone and lidocaine were administered. after 40 hours and despite correction of acidosis, she suddenly developed cardiac arrest and after two times of cpr, was announced dead. 2.3. case 3 a 17-year-old man was admitted to ed due to consumption of one alp tablet 2.5 hours before admission. vital signs were: rr=1 /min, o2sat=95% (in room air), pr=77/min and bp=65/pulse mmhg on admission. seven hours later he was transferred to icu. on admission to icu blood pressure was not detectable, pr=120/min and spo2=80%. abg revealed ph=7.18, pco2=44.7, hco3=16.8 meq/l and scvo2=50%. he received iv fluid therapy in addition to infusion of norepinephrine and dopamine, digoxin 0.5 mg iv, vitamin e 100mg/daily, vitamin c 1 gram/daily, dexamethasone and nac (9 gram in one hour, 4 grams in 4 hours and 6 grams in 16 hours). hypotension was refractory to hydration and infusion of high dose vasopressors. ecg revealed invert t in v3 to v6 leads and echocardiography showed global hypokinesia and lvef=10-15%. iabp was inserted 4 hours after admission and in the next hour he was intubated. systolic blood pressure was below 6 mmhg despite correction of acidosis and other supportive cares. twenty hours after ingestion he developed sudden cardiopulmonary arrest and after 45 minutes of cpr he died. 3. discussion lethal dose of alp is about 500 mg of a tablet (about a sixth of a tablet). some factors might influence prognosis of patients for example length of exposure of tablet to air, whether it is solved in water or not and length of exposure to water; all these factors affect the rate of phosphine gas release before it is consumed. the most important complications of alp poisoning are cardiovascular problems and in particular toxic myocarditis that might lead to severe heart dysfunction. however, cardiac function may be restored if the patient survives (20). it was reported that use of iabp could be successful in some cases of acute poisoning with severe cardiac dysfunction (21, 22). it seems that, for the first time, iabp was inserted in a 25 year old woman with severe toxicity of alp (consumption of 10 tablets) in 2008, which was not successful (22). siddaiah et al. reported the first successful use of iabp in a 22-year-old woman with cardiogenic shock this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e3 following alp consumption (16). subsequently, the second successful use was reported by mehrpour et al. in a 24-yearold woman in 2013 (7). annually, about 300 cases of alp poisoning are referred to imam reza hospital, to which these 3 cases were admitted, and most of the cases are admitted to icu. due to the high rate of mortality in this type of poisoning and also a documented antidote not being available while there are some reports of successful treatment with iabp, we decided to apply iabp for our cases in addition to other supportive cares. we used iabp in three cases and it was successful in one case and he was discharged from hospital without any complication; yet we did not have success in the other two cases and both died. all cases consumed alp intentionally. more investigations are still needed to decide if iabp insertion is effective or not in cases of alp poisoning. however, the method of selecting appropriate cases is a matter of debate and needs to be investigated more. 4. conclusion: it still cannot be decided whether iabp insertion is effective in cases of alp poisoning or not. it might be reasonable to try this intervention along with other conservative treatments in patients who survive more than 12 hours and consistently suffer from refractory hypotension. 5. appendix 5.1. acknowledgements we appreciate all kind assistance of icu personnel. 5.2. author’s contribution bita dadpour, ahmad bagheri moghaddam, hasan abbaspour , shahrad tajoddini and ali moinipour contributed to study concept, design, and critical revision of the manuscript. bita dadpour and ahmad bagheri moghaddam and vahideh mohammadzadeh participated in the drafting of the manuscript. shahrad tajoddini contributed to revision and final approval of the manuscript. 5.3. conflict of interest none. 5.4. funding this study was conducted without financial support. references 1. mehrpour o. comment on “an update on toxicology of aluminum phosphide”. daru. 2012;20(1):50. 2. mehrpour o, keyler d, shadnia s. comment on aluminum and zinc phosphide poisoning. clinical toxicology. 2009;47(8):838-9. 3. mehrpour o, jafarzadeh m, abdollahi m. a systematic review of aluminium phosphide poisoning. archives of industrial hygiene and toxicology. 2012;63(1):61-73. 4. shadnia s, mehrpour o, soltaninejad k. a simplified acute physiology score in the prediction of acute aluminum phosphide poisoning outcome. 2011. 5. shadnia s, mehrpour o, abdollahi m. unintentional poisoning by phosphine released from aluminum phosphide. human & experimental toxicology. 2008;27(1):879. 6. mehrpour o, singh s. rice tablet poisoning: a major concern in iranian population. human & experimental toxicology. 2010;29(8):701-2. 7. mehrpour o, amouzeshi a, dadpour b, oghabian z, zamani n, amini s, et al. successful treatment of cardiogenic shock with an intraaortic balloon pump following aluminium phosphide poisoning. archives of industrial hygiene and toxicology. 2014;65(1):121-7. 8. hashemi-domeneh b, zamani n, hassanianmoghaddam h, rahimi m, shadnia s, erfantalab p, et al. a 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therapy: use of the intra-aortic balloon pump. annals of emergency medicine. 1987;16(12):1381-3. 22. chacko j, shivaprasad c. fatal aluminium phosphide poisoning due to myocardial depression refractory to high dose inotropic support and intra-aortic balloon counterpulsation. indian journal of critical care medicine. 2008;12(1):37. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion conclusion: appendix references archives of academic emergency medicine. 2020; 8(1): e87 or i g i n a l re s e a rc h identification of serum biomarkers for differentiating epileptic seizures from psychogenic attacks using a proteomic approach; a comparative study mohsen parvareshi hamrah1∗, mostafa rezaei tavirani2, monireh movahedi1, sanaz ahmadi karvigh3 1. department of biochemistry, faculty of biological science, north tehran branch, islamic azad university, tehran, iran. 2. proteomics research center, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 3. department of neurology, sina hospital, tehran university of medical sciences, tehran, iran. received: september 2020; accepted: september 2020; published online: 29 october 2020 abstract: introduction: differentiating actual epileptic seizures (ess) from psychogenic non-epileptic seizures (pnes) is of great interest. this study compares the serum proteomics of patients diagnosed with ess and pnes. methods: eight patients with seizure (4 with pnes and 4 with tle (temporal lope epilepsy)) were enrolled in this comparative study. venous blood samples were drawn during the first hour following the seizure. standard protein purification technique was employed and proteins were subsequently separated via 2-d electrophoresis. after comparison of the serum proteomes from the two groups, protein expression was analyzed. the differentially expressed bands were determined using both matrix-assisted laser ionization time-of-flight (maldi/tof) and electrospray ionization quadruple mass spectrometry (ms). results: this study identified 361 proteins, the expression of 110 proteins increased, and 87 proteins decreased in the pnes group compared with tle group. four separate proteins were finally identified with maldi/tof ms analysis. compared with pnes group, alpha 1-acidglycoprotein 1, ceruloplasmin, and s100-β were down-regulated and malate dehydrogenase 2 was up-regulated in the serum of tle patients. conclusion: our results indicated that changes in serum levels of s100-β, ceruloplasmin, alpha 1-acidglycoprotein 1, and malate dehydrogenase 2 after seizure could be introduced as potential markers to differentiate es from pnes; however, more advanced studies are required to reach a better understanding of the underlying mechanisms. keywords: epilepsy; proteomics; biomarkers; diagnosis, differential; emergency service, hospital cite this article as: parvareshi hamrah m, rezaei tavirani m, movahedi m, ahmadi karvigh s. identification of serum biomarkers for differentiating epileptic seizures from psychogenic attacks using a proteomic approach; a comparative study. arch acad emerg med. 2020; 8(1): e87. 1. introduction psychogenic non-epileptic seizures (pnes) neither cause changes in paroxysmal behaviors, nor make changes in ictal, periand inter-ictal electroencephalography (eeg), both of which are characteristics of epileptic seizures (ess) (1). temporal lobe epilepsy (tle), the most common type of epilepsy in humans, is frequently associated with hippocampal sclerosis, cognitive deficit, and pharmaco-resistant seizures (2, 3). up to 80% of the patients who have been diagnosed with ∗corresponding author: mostafa rezaei tavirani; proteomics research center, school of allied medical sciences, darband street, tehran, iran. email: tavirany@yahoo.com, tel: 00989122650447, https://orcid.org/00000003-1767-7475 pnes via video-electroencephalography (veeg) were at least on one anti-epileptic drug (aed) at the time of diagnosis (4). around 5–20% of patients admitted to epilepsy wards to be monitored with veeg are diagnosed with pnes and 20-30% of patients with intractable ess are also differentially diagnosed with pnes (5). misdiagnosis results in years of improper medical treatment, which apart from the financial burden affecting their social life, could cause loads of undesirable and sometimes even unbearable side-effects in patients (6-8). the gold-standard approach to diagnose psychogenic non-epileptic seizures (pnes) is veeg, in which a typical es episode in absence of any change in the ictal tracing is recorded. but the technique has its own limitations; it demands prolonged hospitalization, is not available in many countries, most patients cannot afford it, and is this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. parvareshi hamrah et al. 2 not always able to recognize the seizure episode. therefore, globally, scientists are testing other diagnostic approaches to differentiate ess from pnes. in this regard, various diagnostic biomarkers are gathering more and more attention. comparative proteomic analysis is a powerful diagnostic tool by which the onset, progression, and prognosis of the diseases could be determined in humans. it is especially helpful when the mechanism of a biological process is being investigated, since the technique makes it possible to simultaneously identify a large number of proteins and their alterations, each of which corresponds to a certain pathological condition. the present study aimed to identify differentially expressed proteins, which can differentiate ess from pnes. 2. methods 2.1. study design and setting in this comparative cross-sectional study, out of all patients with prior history of recurrent seizures, admitted to epilepsy monitoring unit (emu) of sina hospital, tehran, iran, a total of 8 patients (4 patients suffering from tle and 4 patients suffering from pnes) were enrolled. after comparison of the serum proteomes from the two groups, protein expression was analyzed and differentially expressed bands were determined. written informed consent was obtained from all patients before entering the study. all procedures performed on human subjects in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 helsinki declaration and its later amendments or comparable ethical standards. additionally, the ethics committee of shahid beheshti university of medical sciences approved of this study under the registration number ir.sbmu.retech.rec.1397.289. 2.2. data gathering the variables considered for data collection were patient’s age, sex, duration and frequency of epilepsy, related risk factors, and received medications. the exclusion criteria of the study included using psychoactive drugs or medications other than antiepileptic drugs (aed), and having neurologic or psychiatric diseases or a recent brain trauma. in order to obtain habitual events, video-eeg (veeg) monitoring was performed for all patients. a skilled epileptologist identified the type of epilepsy considering ictal and interictal eeg results and the semiology of the seizures. 2.3. sample preparation blood samples were drawn within 1 hour following seizure episodes in patients. samples were centrifuged at 4000 rpm for 10 minutes and serum aliquots were kept at –80 ◦c until needed. 2.4. proteomic experiment 2d-electrophoresis materials used were made by ge healthcare life sciences (http:// www.gelifesciences.com) and serva company (http://www.serva.de). pooling was performed for the two groups, separately, and protein extraction was done using 2-de clean-up kit (ge healthcare). the concentrations of the protein were reported using 2-de quant kit (ge healthcare) and then 2-de performed on triple replicate samples. the first dimension, isoelectric focusing (ief), separates proteins based on their isoelectric point (pi). before this phase, immobilized ph gradient (ipg) strips were passively rehydrated for 8 hours. then, isoelectric focusing (ief) was carried out using bio-rad protean ief cell, 11 cm nonlinear ipg with ph range 4-7 for 7.5 hours at 20 ◦c, according to the bio-rad protocol. after that, the ipg strips were equilibrated in equilibration solution (serva kit) for 30 minutes at room temperature. the next step consisted of separation of the proteins based on molecular weight (mw ) via hpe flattop tower (horizontal electrophoresis) using 2d hpe™ double-gel 12.5 % kit (serva company) for 3.5 hours. after electrophoretic separation of the proteins, gels were stained using serva hpe™coomassie® staining kit according to the manufacturer’s instructions. stained gels were then scanned using a calibrated gs-800 densitometer scanner (bio-rad) (9). protein expression of the two samples was quantified and qualified using progenesis same spots software as an image analyzer. 2.5. statistical analysis the cut-off point was considered 1.5-fold increase or decrease. statistically significant differences (p≤0.05) in spot intensities were determined via one-way anova analysis as a multivariate statistical analysis tool analyzing gel images using the alignment method. the criteria for gel analysis were 1.5-fold change. finally, using maldi-tof ms, the candidate spot was evaluated. protein spots before treatment with trypsin, were de-stained and treated with dithiothreitol (dtt) and iodoacetamide for reduction and alkylation, respectively. in the end, to identify the protein, the extracted peptides were assessed by ms and the spectra were entered into mascot (http://www.matrixscience.com). 3. results 3.1. demographic features of different study groups v-eeg showed that 4 patients (2 male and 2 female) with the mean age of 37.5 ± 7.76 years had mesial tle and 4 patients (2 male and 2 female) with the mean age of 33.25 ± 18.7 years had pnes. patients in pnes group experienced seizures with the frequency range of 3-30 per month, while the frequency this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e87 figure 1: representative two-dimensional electrophoresis gels of serum proteins of patients with temporal lobe epilepsy (a) and psychogenic non-epileptic seizures (b). range of seizure experience for the patients in es group was 2-4 episodes per month. the duration of the disease was 312 years in pnes group and 4-24 years in es group. all members of the study population were on multidrug therapy. two patients (one in pnes group and one in es group) were on psychiatric medications (antidepressants or neuroleptics). 3.2. proteomic analysis serum analysis of es group (figure 1a) and pnes group (figure 1b) identified alteration in the expression of 197 proteins out of the total of 361 identified proteins, 110 (55.9%) of which showed up-regulation, and 87 (44.1%) showed downregulation in the pnes group when compared to es group. as summarized in table 1, four distinct proteins (s100-β, malate dehydrogenase 2, alpha 1-acid glycoprotein 1, ceruloplasmin) were identified through maldi/tof ms analysis. the expression of alpha 1-acid glycoprotein 1, ceruloplasmin, s100-β had decreased in the serum of patients in es group, and malate dehydrogenase 2 had increased in es group. table 2 demonstrates the identified proteins’ principal cellular and molecular functions. 4. discussion our results showed significant differences between the serum levels of four proteins including ceruloplasmin, malate dehydrogenase 2 (mdh2), s100b, and alpha-1-acid glycoprotein 1 in es and pnes groups, which can be considered as suitable biomarkers for distinguishing pnes from es. over the past decades, a wide variety of diagnostic approaches have been developed to identify pnes, leading to introduction of electroencephalography (veeg) as the gold standard method to differentiate pnes from es (10). despite the favorable results, using this approach is associated with some challenges, including high cost and lack of availability for all clinical centers. moreover, veeg assessment only confirms the epileptic discharge in patients suffering from es, whereas it is not a confirmation test for those with pnes (1, 11). a glance at the misdiagnosed pnes rate reveals the importance of definitive diagnosis of true pnes cases. it is reported that about 20% of patients with manifestations of refractory epilepsy have pnes. moreover, approximately 30% of cases that are diagnosed as refractory epilepsy and referred to surgery suffer from pnes (12). thus, the searches for new biological and psychological markers to identify pnes cases continues. in this light, using blood biomarkers for diagnosis of pnes is of interest to researchers because of their low cost and sample availability. unfortunately, despite the extensive efforts in this context, no reliable biomarker has been discovered to certainly distinguish pnes from the other types of seizure. to date, various biomarkers such as cortisol (13, 14), prolactin (prl) (15, 16), neuron-specific enolase (nse) (17, 18), brain-derived neurotrophic factor (bdnf) (19), and ghrelin and nesfatin-1 (20) have been discussed as potential markers to differentiate es from pnes. among them, prl showed to have the highest sensitivity. measuring serum level of prl within 20-30 min after the seizure has been recthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. parvareshi hamrah et al. 4 table 1: differentially expressed proteins in the serum of patients with temporal lope epilepsy (tle) compared to psychogenic non-epileptic seizures (pnes) group spot no. gene name uniprot code pi/mw (da)1 pi/mw (da)2 fold regulation* 311 s100-β p04271 4.57/10.713 4.84/10 3.5 up 258 mdh2 p40926 8.92/35.503 6.52/22 2.3 down 248 orm1 p02763 4.93/23.52 3.93/25 2.3 up 59 cp p00450 1.065/5.44 5.67/140 2.3 up 61 cp p00450 1.065/5.44 5.73/128 5.3 up 62 cp p00450 1.065/5.44 5.81/128 2.8 up 1: theoretical; 2: observed; *: in pens group; mw: molecular weight; pi: isoelectric point; da: dalton mdh2: malate dehydrogenase2; orm1: alpha 1acid glycoprotein 1; cp: ceruloplasmin. table 2: cellular and molecular functions of identified proteins protein name function s100-β calcium ion binding; calcium-dependent protein binding; identical protein binding; protein binding; protein homo dimerization activity; rage receptor binding; s100 protein binding; tau protein binding; zinc ion binding mdh2 l-malate dehydrogenase activity; malate dehydrogenase (nadp+) activity; protein self-association orm1 protein binding cp chaperone binding; copper ion binding; ferroxidase activity the function of each protein was identified using the uniprot database. mdh2: malate dehydrogenase 2; orm1: alpha 1acid glycoprotein 1; cp: ceruloplasmin. ommended by the american academy of neurology (aan) as a helpful test to differentiate es from pnes (17, 20-22). it is important to measure prl levels as early as possible as it returns to baseline 2-6 hours after the seizure (23). according to a study done by d’alessio et al. measuring prl after seizure had the sensitivity and specificity of 69% and 93% in differentiation of es from pnes, respectively (15). high serum prl levels should be taken seriously, as it is susceptible to alteration by different physiological and pathological conditions, and different medications (23). serum creatinine kinase (ck) is one of the elements whose level after seizure has been considered medically related to differentiating es from pnes (sensitivity of 14.6% to 87.5% and specificity of 85% to 100%) (24, 25). it is important to mention that increased serum ck levels should also be taken seriously, as many different clinical complications could cause it (26, 27). in recent years, progress in the field of proteomics has opened a promising window to find new candidates in the context. in the present study, serum proteins of patients suffering from es and pnes were compared. it is important to state that the difference in protein expression in the two gels can help us identify protein markers that are vital for diagnosis and treatment of related diseases. in our previous effort, up-regulated proteins with higher molecular weights and high isoelectric point were reported to be present in patients with temporal lobe epilepsy (tle) compared with pnes samples. our study showed that a critical event that can be used for discriminating pnes from es is damage to blood brain barrier in epileptic seizure. thereby, to have a thorough view of es, the deregulated proteins need to be identified (28). ceruloplasmin is a ferroxidase enzyme that belongs to a multicopper oxidase family. this enzyme possesses three copper sites in its structure and carries the major part of copper ions (>95%) in plasma. ceruloplasmin is also involved in iron metabolism (29). our findings indicated that patients suffering from pnes had a higher amount of ceruloplasmin compared to those with es. so far, many studies have shown the differences in cu2+ concentration among patients with es (30, 31). for instance, hamed et al. found that the serum concentration of cu2+ in untreatedes patients was significantly higher than patients receiving anticonvulsant drugs (32). however, no study has compared the serum levels of ceruloplasmin in patients suffering from es and pnes. according to our result, the higher concentration of ceruloplasmin in patients with pnes gives a hint for further investigations on the serum levels of cu2+ for differential diagnosis of pnes from es. for the first time in literature, we found the difference between mdh2 levels in the serum samples of patients with es and pnes. our results showed a higher amount of mdh2 in patients with epilepsy compared with those suffering from pnes. it is reported that mdh2 is a negative regulator of scn1a gene expression at the posttranscriptional level (33). scn1a gene encodes the voltage-gated sodium channel αsubunit type i protein (nav1.1) that plays an important role in brain excitability. a wide variety of studies have confirmed the correlation between the down-regulation of scn1a and epilepsy (34, 35). chen et al. reported that mdh2 directly binds to the 3’ utr region of scn1a mrna, which decreases this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e87 the mrna stability. accordingly, the forced overexpression of mdh2 in hek-293 cells resulted in down-regulation of scn1a expression. they also found that there was an inverse correlation between the amount of nav1.1 and mdh2 proteins in the hippocampus of seizure mice (33). this finding suggests the potential of mdh2 as a predictive biomarker of epilepsy. s100-b protein is mainly produced by astrocytes that are involved in diverse biological events such as cell proliferation, differentiation, apoptosis, and migration (36, 37). this ca2+ binding protein exhibits characteristics that make it a suitable candidate to be used as a biomarker of brain damages (38). increase in the serum level of s100-b in patients with epilepsy and infants suffering from epileptic seizures has revealed the high potency of this protein for clinical diagnosis of epilepsy (39, 40). it has been suggested that s100b protein plays a part in the anti-epileptogenic effect of astrocytes. following the electrical kindling of the amygdala, dyck et al. reported that s100b-knockout mice had more rapid and severe seizures compared with normal mice (41). in a study conducted by chang et al., the serum levels of s100b in thirty-four patients with temporal lobe epilepsy (tle) were analyzed. in their study, s100b serum level in patients with more than two seizures per month was significantly higher than those with less than two seizure episodes per month (42). however, using s100-b protein as an epilepsy biomarker is controversial and some studies have reported no significant differences between the serum levels of s100ß in patients with tle and controls (43, 44). recently, asadollahi et al. evaluated the serum level of s100-b in patients with epilepsy, pnes, and healthy individuals. according to their findings, s100-b was significantly higher in patients suffering from es compared with those with pnes as well as healthy controls. on the other hand, patients with pnes showed a higher concentration of s100-b in their sera compared with controls (45). in the current study, we found that the expression rate of s100-b protein was remarkably higher in patients with pnes compared to es patients. this finding was not in line with those observed in the study by asadollahi et al., which may be due to the larger sample size in their study. however, it seems that further investigations are needed to confirm the true potential of s100-b for differential diagnosis of pnes and es. in the present study, patients with pnes had higher levels of alpha-1-acid glycoprotein than the patients with es patients. alpha-1-acid glycoprotein with the molecular weight of 41-43 kd contains 45% carbohydrate in its structure (46). this glycoprotein is one of the acute-phase proteins that remarkably increases in response to various situations including infections, surgery, traumas, and myocardial infraction (47). to date, few studies have been conducted on changes in the serum level of alpha-1-acid glycoprotein in patients with epilepsy. morita et al. showed that the serum level of alpha-1-acid glycoprotein in patients receiving enzyme-inducer anticonvulsant drugs such as carbamazepine was not significantly different from that of those receiving non-inducer drugs; but the serum level of this protein in the patients with poorly controlled seizures was significantly higher than those with well-controlled seizures (47). in another study, the serum levels of alpha-1-acid glycoprotein in patients who underwent electroconvulsive therapy were analyzed. it was reported that the serum levels of this protein were not consistently altered during electroconvulsive therapy (48). these findings show that alpha-1-acid glycoprotein can be considered as an independent biomarker for es, which is not affected by the type of therapeutic approaches. 5. limitation low sample size and lack of easy access to patients was one of the limitations of the study. 6. conclusion our results indicated that changes in serum levels of s100-β, ceruloplasmin, alpha 1-acid glycoprotein 1, and malate dehydrogenase after seizure could be introduced as potential markers to differentiate es from pnes; however, more advanced studies are required to reach a better understanding of the underlying mechanisms. 7. declarations 7.1. acknowledgements the authors would like to thank the proteomics research center, shahid beheshti university of medical sciences, tehran, iran for their support, cooperation, and assistance throughout the study. 7.2. author contribution all authors had an equal role in the design, work, statistical analysis, and manuscript writing. 7.3. funding/support this study was funded by the proteomics research center, shahid beheshti university of medical sciences. 7.4. conflict of interest the authors declare that they have no conflict of interest. references 1. bodde nm, brooks jl, baker ga, boon pa, hendriksen jg, aldenkamp ap. psychogenic non-epileptic this 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human status epilepticus. neurology. 1995;45(6):1134-7. 44. leutmezer f, wagner o, baumgartner c. serum s-100 protein is not a suitable seizure marker in temporal lobe epilepsy. epilepsia. 2002;43(10):1172-4. 45. asadollahi m, simani l. the diagnostic value of serum uchl-1 and s100-b levels in differentiate epileptic seizures from psychogenic attacks. brain research. 2019;1704:11-5. 46. fournier t, medjoubi-n n, porquet d. alpha-1-acid glycoprotein. biochimica et biophysica acta (bba)-protein structure and molecular enzymology. 2000;1482(12):157-71. 47. morita k, yamaji a. changes in the concentration of serum alpha 1-acid glycoprotein in epileptic patients. european journal of clinical pharmacology. 1994;46(2):137-42. 48. devane cl, lim c, carson sw, tingle d, hackett l, ware mr. effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein. biological psychiatry. 1991;30(2):116-20. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e21 le t t e r to ed i to r coronavirus pandemic and worries during pregnancy; a letter to editor farzaneh rashidi fakari1, masoumeh simbar2∗ 1. student research committee, department of midwifery and reproductive health, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. midwifery and reproductive health research center, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. received: march 2020; accepted: march 2020; published online: 16 march 2020 cite this article as: rashidi fakari f, simbar m. coronavirus pandemic and worries during pregnancy; a letter to editor. arch acad emerg med. 2020; 8(1): e21. dear editor: coronavirus (covid-19) is a new respiratory disease that is spreading widely throughout the world(1). there is no valid information available on pregnant women and their complications. but given previous epidemics (sars and mers), as well as mental and physical changes during pregnancy (2), pregnant women are more likely to be affected by the virus. on the other hand, the coronavirus epidemic has created stress and anxiety for pregnant women in different parts of the world. concern and stress in pregnancy are associated with side effects such as preeclampsia, depression, increased nausea and vomiting during pregnancy, preterm labor, low birth weight, and low apgar score (3-7). in the coronavirus pandemic, pregnant women cited the following reasons for their concerns: many pregnant women have had a birth plan before the pandemic, but are currently worried about how their families (mothers) will be present, given the urban and quarantine constraints; moreover, even if there is no inter-urban restriction, they may be worried about their families being infected during transportation. many pregnant women do not go to visit their physicians due to concerns that they may be exposed to the coronavirus in the hospital environment or on the way to the hospital and may be post-term. or on the contrary, due to stress and worry they want an early termination and elective cesarean section. many pregnant mothers are employed and constantly use sodium hypochlorite and alcohol detergents to control and prevent the virus, which can lead to poisoning. some other pregnant mothers might become highly stressed and anxious, and overuse these detergents. some mothers are ∗corresponding author: masoumeh simbar; midwifery and reproductive health research center, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. postal code: 9115386991, tel: +982188202512, fax: 02133020695, e-mail: msimbar@gmail.com worried about their fetal or their neonate being born. also, some mothers worry about postpartum such as breastfeeding, and neonatal care (postpartum vaccination, screening). increasing mothers’ awareness about the transmission of coronavirus, risk factors, and red flags, as well as providing tele-counseling for pregnancy care and tele-triage could help reduce their anxiety and worry. it is also recommended that in cities where home birth and home services after birth are available, the medical team provide these services at home while maintaining safety. 1. declarations 1.1. acknowledgment none. 1.2. author’s contribution both authors made a substantial contribution to writing of the paper draft and met the four criteria for authorship recommended by the international committee of medical journal editors. authors orcids farzaneh rashidi fakari: 0000-0001-7498-475x masoumeh simbar: 0000-0003-2843-3150 1.3. conflict of interest none. 1.4. funding and support none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem f. rashidi & m. simbar 2 references 1. organization wh. novel coronavirus (2019-ncov ) situation report-9, 29 january 2020. geneva, switzerland.2020. 2. schwartz da, graham al. potential maternal and infant outcomes from coronavirus 2019-ncov (sars-cov2) infecting pregnant women: lessons from sars, mers, and other human coronavirus infections. viruses. 2020;12(2):194. 3. qiao y, wang j, li j, wang j. effects of depressive and anxiety symptoms during pregnancy on pregnant, obstetric and neonatal outcomes: a follow-up study. journal of obstetrics and gynaecology. 2012;32(3):237-40. 4. field t, diego m, hernandez-reif m, figueiredo b, deeds o, ascencio a, et al. comorbid depression and anxiety effects on pregnancy and neonatal outcome. infant behavior and development. 2010;33(1):23-9. 5. rubinchik sm, kablinger as, gardner js. medications for panic disorder and generalized anxiety disorder during pregnancy. primary care companion to the journal of clinical psychiatry. 2005;7(3):100-5. 6. alder j, fink n, bitzer j, hosli i, holzgreve w. depression and anxiety during pregnancy: a risk factor for obstetric, fetal and neonatal outcome? a critical review of the literature. the journal of maternal-fetal & neonatal medicine. 2007;20(3):189-209. 7. littleton hl, breitkopf cr, berenson ab. correlates of anxiety symptoms during pregnancy and association with perinatal outcomes: a meta-analysis. american journal of obstetrics and gynecology. 2007;196(5):424-32. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2021; 9(1): e8 https://doi.org/10.22037/aaem.v9i1.948 or i g i n a l re s e a rc h baseline characteristics and outcomes of patients with head and neck burn injuries; a cross-sectional study of 2181 cases soudabeh haddadi1∗, arman parvizi1, reza niknama2, shadman nemati3, ramyar farzan4, ehsan kazemnejad3 1. anesthesiology research center, department of anesthesiology, alzahra hospital, guilan university of medical sciences, rasht, iran. 2. guilan university of medical sciences, rasht, iran. 3. otorhinolaryngology research center, department of ent, head and neck surgery, amiralmomenin hospital, guilan university of medical sciences, rasht, iran. 4. department of general surgery, velayat hospital, guilan university of medical sciences, rasht, iran. received: november 2020; accepted: november 2020; published online: 11 december 2020 abstract: introduction: despite recent progress in treatment of burn injuries, head and neck burn and its complications is still considered a challenge. this study aimed to evaluate the baseline characteristics and outcomes of patients with head and neck burn. methods: in this retrospective cross-sectional study, the medical profiles of patients with head and neck burn referring to a burn care center during 2 years were reviewed and analyzed regarding the baseline characteristics and outcomes of participants. results: 392 (17.97%) cases suffered from head and neck burns. the mean burn percentage of participants was 29.31 ± 24.78, and 126 (32.14%) cases required tracheal intubation. there was a direct correlation between length of hospital stay and the degree of burn (p < 0.001). the length of hospitalization for patients burned by electricity was longer than those burned by other mechanisms (p = 0.003). there was a significant correlation between degree of burn and abnormal laryngoscopy findings (p = 0.036), developing acute respiratory distress syndrome (ards) (p < 0.001) and pneumonia (p < 0.001), need for mechanical ventilation (p < 0.001), and mortality rate (p < 0.001). conclusion: based on the findings of the present study, the prevalence of head and neck burn injuries was about 18% and 32.14% of these cases required airway management. 19 (4.85%) cases developed ards, 41 (10.46%) developed pneumonia, and 50 (12.76%) cases died. there was a significant correlation between degree of burn and abnormal laryngoscopy findings, developing ards and pneumonia, need for mechanical ventilation, and mortality rate. keywords: burns; patient outcome assessment; intubation, intratracheal; head; neck; respiration, artificial cite this article as: haddadi s, parvizi a, niknama r, nemati s, farzan r, kazemnejad e. baseline characteristics and outcomes of patients with head and neck burn injuries; a cross-sectional study of 2181 cases. arch acad emerg med. 2021; 9(1): e8. 1. introduction it is estimated that 180,000 people die from burn injuries every year worldwide. non-fatal burns are among the leading causes of disability-adjusted life years (dalys), which often occur in lowand middle-income countries. according to the world health organization (who), nearly 11 million people ∗corresponding author: soudabeh haddadi; anesthesiology research center, department of anesthesiology, alzahra hospital, rasht, iran. email: so_haddadi@yahoo.com, phone: +981332338306-7, orcid:0000-0002-05853235 were severely burned worldwide in 2004, such that they required medical care (1). the proportion of head and neck burns in burn center admissions has been estimated as 47% in a study, indicating the importance of this type of injury (2). prevention of primary injury should always be a priority, but when the injury occurs, the primary goal should be to prevent the progression of injury and ensuring patient survival (3). burns can cause extensive and devastating injury to the face and neck. complications of burns can be divided into two categories: cosmetic and functional. functional complications include airway injuries, carbon monoxide poisoning, corneal and eye burns, chondrites, and ear injuries (3-6). the most important part in the initial evaluation of patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haddadi et al. 2 after burns is to examine the airways and support them (3, 4). it has been estimated that approximately 13,000 to 22,000 people suffer from inhalation burns each year in the united states (4). although the patient may be able to breathe spontaneously in the early hours after the burn, it is still possible for the injury to spread and affect the entire respiratory tract (3). inhalation injury is the third leading predictor of death due to burn after total body surface area (tbsa) burn and aging. the mortality rate of burn victims with inhalation injuries has been estimated to be about 30%, while only 2% of burn patients without respiratory injury die (4). immediate primary care can have a significant impact on the rate of primary injury, its progression, and its long-term outcomes (2, 3). inhalation burns have still remained a major challenge for anesthesiologists as well as intensive care and rehabilitation specialists worldwide, and there is no agreement on the appropriate and systematic evidence-based approach for treating the patients in the acute phase (4). in order to plan for prevention and improving the level of care and outcomes of the head and neck burns, the first step is to assess the needs and outcomes of burn patients. therefore, the present study aims to evaluate baseline characteristics and outcomes of patients with head and neck burns. 2. methods 2.1. study design and setting this retrospective, cross-sectional study was conducted on patients referring to velayat hospital (an academic burn care center in rasht, north iran), following face, head, neck, and airway burn injuries from april 2017 to the end of march 2019. using the patients’ profiles, the baseline characteristics and outcomes of patients were collected and analyzed. the study protocol was approved by vice president for research of guilan university of medical sciences (ethics code: ir.gums.rec.1397.394). researchers adhered to the principles of helsinki ethics recommendations and confidentiality of patients’ data. 2.2. participants all of the patients referring to velayat hospital, following face, head, and neck burn injuries from april 2017 to the end of march 2019 were included. those who were discharged in less than 24 hours were excluded from the study. 2.3. data gathering using a predesigned checklist and census sampling, demographic characteristics, including age, gender, percentage of burn, etiology, burn scenario, comorbidity, first medical treatment, airway condition, need for mechanical ventilation, laryngoscopy finding, respiratory complications (acute respiratory distress syndrome (ards), pneumonia), length of hospital stay, and mortality rate were collected from the patients’ profiles. to determine the frequency of head and neck burns, all the records of head and neck burns and those unrelated to head and neck burns were counted in the specified time period. a medical student was responsible for data gathering. the percentage of burn was measured using rule of 9. the patients became candidates for intubation in case of drop in their saturation with suspected airway injury, presence of dyspnea, tachypnea, cyanosis, or loss of consciousness. 2.4. statistical analysis data were analyzed using spss version 21.0 and presented as frequency (%) or mean ± standard deviation (sd). a p-value less than 0.05 was considered to be statistically significant. 3. results 3.1. baseline characteristics of participants out of the 2181 patients referring to the studied hospital during 2017-2019, 392 (17.97%) cases suffered from head and neck burns. the mean age of patients was 37.14 ± 18.80 (0.5– 92) years (75.00% male). table 1 shows the baseline characteristics and outcomes of studied patients. the mean burn percentage of participants was 29.31 ± 24.78 (3 – 100) percent of body surface area (54.34% with 10-30% burns). flame was the most common burn mechanism (52.3%) and the mean length of hospital stay was 6.02 ± 7.0 (1 -51) days. 36.73% of females were burned by hot liquids, while the cause of burn in 58.16% of males was flame (p < 0.001). there were no statistically significant differences between male and female participants regarding the degree of burn (p = 0.109), airway condition (p = 0.861), laryngoscopic findings (p = 0.908), need for mechanical ventilation (p = 0.248), incidence of ards (p = 0.892), incidence of pneumonia (p = 0.775), and mortality (p = 0.861). 3.2. outcomes 126 (32.14%) cases required tracheal intubation. laryngoscopic findings (in patients who required airway management) showed that 27 (21.43%) cases had erythema and edema. 19 (4.85%) cases developed ards, 41 (10.46%) developed pneumonia, and 50 (12.76%) cases died. there was a direct correlation between length of hospital stay and the degree of burn (p < 0.001). the length of hospitalization for patients who were burned by electricity was longer than those burned by other mechanisms (p = 0.003). table 2 shows the correlation between laryngoscopic findings and baseline characteristics as well as outcomes of cases that underwent laryngoscopy. in addition, the correlation between mortality rate and baseline characteristics and outcomes of cases this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e8 table 1: baseline characteristics of patients who referred to the studied hospital following head and neck burn injuries variables number (%) gender female 98 (25.0) male 294 (75.0) age (years) > 20 58 (14.8) 20-40 170 (43.4) 40-60 116 (29.6) ≥ 60 48 (12.2) mechanism of burn flame 205 (52.3) liquids 85 (21.7) electricity 13 (3.3) vapor 36 (9.2) chemicals 8 (2.0) unknown 45 (11.5) outcomes need for tracheal intubation 126(32.14) ards 19 (4.85) pneumonia 41 (10.46) mortality 50 (12.76) mean length of stay 6.02 ± 7.23 laryngoscopic view of candidate for intubation normal 99 (78.57) erythema, edema 27 (21.43) data are presented as mean ± standard deviation or frequency (%). ards: acute respiratory distress syndrome. is shown in table 3. there was a significant correlation between degree of burn and abnormal laryngoscopy findings (p = 0.036), developing ards (p < 0.001) and pneumonia (p < 0.001), need for mechanical ventilation (p < 0.001), and mortality rate (p < 0.001). 4. discussion based on the findings of the present study, the prevalence of head and neck burn injuries was about 18% and 32.14% of these cases required airway management. 19 (4.85%) cases developed ards, 41 (10.46%) developed pneumonia, and 50 (12.76%) cases died. there was a significant correlation between degree of burn and abnormal laryngoscopy findings, developing ards and pneumonia, need for mechanical ventilation, and mortality rate. the prevalence of head and neck burn injuries in this study was much lower than that in the study by hau tian et al. (2020) who reported the percentage of head and neck burns among 1126 chinese patients as 65.63% (7). in the present study, 75% of the patients were male and 43.4% were in the age group of 20-40 years old, which was consistent with the report by the who (1). this result was also similar to the study by hamilton et al. (2018) performed in the united states, in which 66% of the patients were male, however most of them were in their 40s (8). also, in the study conducted by hau tian (2020) in china, 73.8% of the patients with head and neck burns were men (7), which was in line with the present study. this can be due to occupational exposure and workplace accidents. however, in another study conducted by costa santos (2016), women suffered from head and neck burns more than men, and the correlation between burn complications and gender was found to be statistically significant (9). in their study, burd et al. (2010) found that although patients may have spontaneous breathing in the first hours after a burn, there is always the possibility of spreading burn injury and edema throughout the respiratory tract (3), which can be caused by edema in the head and neck following the inhalation of vapor, smoke, or aspiration of burning liquids (3). in this study, only 32.14% of the patients needed intubation; 78.57% of them had normal glottis and 21.43% had erythema and edema. also, 11.11% of the patients (n=3) with edematous and erythematous view in their laryngoscopy did not need intubation. this rate was significantly lower than the results of the study by belba et al. (2008), who estimated the intubation rate for the patients with head and neck burns as 39% (10). the presence of soot in the mouth in facial and body burns necessitates a fiberoptic laryngoscopy, as it stabilizes the airways in the case of cutaneous lesions, inflammation, blisters, and significant wounds in these patients. the classic symptoms of inhalation injury, such as stridor, itching, shortness of breath, and dysplasia confirm the need for tracheal intubation (6). the results of the present study showed that patients with secondand third-degree burns had a higher percentage of abnormal laryngoscopy. also, patients with comorbidities had a higher rate of abnormal laryngoscopy (more than 3 times). regarding the outcomes of burns based on laryngoscopy, it could be stated that intubation was observed in 88.89%, ventilation in 77.78%, ards in 40.74%, pneumonia in 66.67%, and mortality in 70.37% of the patients with abnormal laryngoscopy; these figures were significantly higher than those in the patients with normal laryngoscopy. costa santos et al. (2016) found that head and neck burns significantly increased the incidence and severity of pneumonia in burn patients (9). in the present study, 10.46% of the patients developed pneumonia. of the 392 patients with head and neck burns, 89.8% did not require mechanical ventilation (10.2% needed it) and ards was observed in 4.85% of the patients. however, in the study conducted by miller et al. (2009), ards was identified as one of the leading causes of mortality, the incidence of which was estimated to be 20% (11). in the study by madnani et al. (2016), out of 40 patients in the emergency room, 8 patients required emergency intubation this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haddadi et al. 4 table 2: correlation between laryngoscopic findings and baseline characteristics as well as outcomes of cases who underwent laryngoscopy variables laryngoscopic findings p normal (n= 99) abnormal* (n = 27) burn degree second-degree 27 (27.27) 5 (18.52) secondto third 63 (63.63) 14 (51.85) 0.036 thirdto fourth 9 (9.10) 8 (29.63) mechanism of burn flame 58 (58.59) 18 (66.67) liquids 5 (5.05) 3 (11.11) vapor 34 (34.34) 2 (7.41) <0.001 chemicals 1 (1.01) 0 (0.00) unknown 1 (1.01) 4 (14.81) comorbidity no 87 (87.88) 21 (77.78) 0.184 yes 12 (12.12) 6 (22.22) ards no 92 (92.93) 16 (59.26) <0.001 yes 7 (7.07) 11 (40.74) pneumonia no 83 (83.84) 9 (33.33) <0.001 yes 16 (16.16) 18 (66.67) mortality no 72 (72.73) 8 (29.63) <0.001 yes 27 (27.27) 19 (70.37) data are presented as frequency (%); abnormal: erythema and edema. ards: acute respiratory distress syndrome. table 3: correlation between mortality rate and baseline characteristics of cases with head and neck burn injuries variables outcome p not survived (n = 50) survived (n = 342) degree of burn second 6 (12.00) 183 (54.79) secondto third 36 (72.00) 143 (42.81) <0.001* thirdto fourth 12 (24.00) 8 (2.40) mechanism of burn flame 35 (70.00) 170 (49.71) liquids 5 (10.00) 80 (23.39) electricity 1 (2.00) 12 (3.51) 0.121 vapor 4 (8.00) 32 (9.36) chemicals 0 (0.00) 8 (2.34) unknown 5 (10.00) 40 (11.70) comorbidity no 34 (68.00) 319 (93.27) 0.027 yes 16 (32.00) 23 (6.73) tracheal intubation no 16 (32.00) 326 (95.32) <0.001 yes 34 (68.00) 16 (4.68) ards no 37 (74.00) 336 (98.25) <0.001 yes 13 (26.00) 6 (1.75) pneumonia no 29 (58.00) 322 (94.15) <0.001 yes 21 (42.00) 20 (5.85) data are presented as number (%). ards: acute respiratory distress syndrome. and their vocal cord edema was positive in laryngoscopy (p = 0.01)(12). in the present study, airway edema was also obthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e8 served in vocal cords (13), and mortality rate following burns was 12.76%. hamilton et al. (2018) in the united states found that although a quarter of patients with head and neck burns suffered from inhalation injuries, mortality occurred in only 2%. the researchers identified airway burns as an important risk factor for predicting mortality (8). the lower incidence of respiratory complications and higher mortality rate in the current study compared to other studies emphasizes the need for proper airway management and its vital role in the prognosis and survival of patients. in the present study, most of the patients had 10-30% burns, 48.95% of which were of the second-degree type. flame was the most common type of burn mechanism among the patients with 52.3%. the mean length of hospital stay was 6.02±7 days. in the study by hamilton et al. (2018), the mean length of hospital stay was 4.4 days and, as in the present study, flame was the most common cause of burns, which occurred locally and superficially (8). in another study, bai et al. (2013) stated that ventilator support was significantly associated with increased length of hospitalization (13). however, in the study by santos et al. (2016), those who were intubated were discharged earlier (9), which may be due to the high incidence of primary mortality in this group. in the present study, the length of hospital stay correlated with degree of burn, burn mechanism, airway condition, intubation, and incidence of adrs and pneumonia. inhalation injuries in patients with head and neck burns are serious and life-threatening, and the management of airways and respiratory outcomes over the hospitalization course of these patients should be taken into consideration. 5. limitations one of the most important limitations was the presence of incomplete patient profiles, which was due to the retrospective fashion of the study. 6. conclusion based on the findings of the present study, the prevalence of head and neck burn injuries was about 18% and 32.14% of these cases required airway management. 19 (4.85%) cases developed ards, 41 (10.46%) developed pneumonia, and 50 (12.76%) cases died. there was a significant correlation between degree of burn and abnormal laryngoscopy findings, developing ards and pneumonia, need for mechanical ventilation, and mortality rate. 7. declarations 7.1. acknowledgment this article has been extracted from dr. reza nicknama’s thesis for achieving his md degree from the faculty of medicine at guilan university of medical sciences. 7.2. author contributions all authors passed the criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding none declared. 7.4. conflict of interest none. references 1. organization wh. burns fact sheet 6 march 2018 [26 august 2020]. available from: https://www.who.int/newsroom/fact-sheets/detail/burns. 2. hoogewerf cj, van baar me, hop mj, bloemen mc, middelkoop e, nieuwenhuis mk. burns to the head and neck: epidemiology and predictors of surgery. burns. 2013;39(6):1184-92. 3. burd a, editor burns: treatment and outcomes. seminars in plastic surgery; 2010: thieme medical publishers. 4. sabri a, dabbous h, dowli a, barazi r. the airway in inhalational injury: diagnosis and management. annals of burns and fire disasters. 2017;30(1):24. 5. haddadi s, marzban s, parvizi a, dadashi a, roshan za, kiyarash ssm. congruency of nasal alar pulse oximetry and arterial blood analysis in patients with burns hospitalized in icu. of. 2017;4:2. 6. herndon dn. total burn care e-book: expert consultonline: elsevier health sciences; 2012. 7. tian h, wang l, xie w, shen c, guo g, liu j, et al. epidemiology and outcome analysis of facial burns: a retrospective multicentre study 2011–2015. burns. 2020;46(3):718-26. 8. hamilton tj, patterson j, williams ry, ingram wl, hodge js, abramowicz s. management of head and neck burns—a 15-year review. journal of oral and maxillofacial surgery. 2018;76(2):375-9. 9. santos dc, barros f, gomes n, guedes t, maia m. face and/or neck burns: a risk factor for respiratory infection? annals of burns and fire disasters. 2016;29(2):97. 10. belba g, gedeshi i, isaraj s, filaj v, kola n, belba m. head and neck burns: acute and late reconstruction. data of burn injury management in 2007. annals of burns and fire disasters. 2008;21(4):203. 11. miller ac, rivero a, ziad s, smith dj, elamin em. influence of nebulized unfractionated heparin and nacetylcysteine in acute lung injury after smoke inhalation injury. journal of burn care & research. 2009;30(2):249-56. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. haddadi et al. 6 12. madnani dd, steele np, de vries e. factors that predict the need for intubation in patients with smoke inhalation injury. ear, nose & throat journal. 2006;85(4):278-80. 13. bai c, huang h, yao x, zhu s, li b, hang j, et al. application of flexible bronchoscopy in inhalation lung injury. diagnostic pathology. 2013;8(1):174. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e5 or i g i n a l re s e a rc h intravenous magnesium sulfate for pain management in patients with acute renal colic; a randomized clinical trial alireza majidi1, fatemeh derakhshani1∗ 1. emergency department, clinical research development unit, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: october 2019; accepted: december 2019; published online: 28 january 2020 abstract: introduction: it seems that magnesium (mg) sulfate can be helpful in controlling the acute pain caused by the stone passing from the ureter by reducing ureter smooth muscle contractions. the present study has been designed with the aim of assessing the role of mg sulfate in controlling the renal colic pain in emergency department (ed). methods: this double blind randomized clinical trial was performed on 18 to 60 year-old patients with acute renal colic presenting to the ed of a teaching hospital during 1 year. patients were allocated to one of the 2 groups receiving either iv morphine or iv mg sulfate using block randomization method and were then compared regarding pain control characteristics and probable side effects. results: 90 patients with the mean age of 37.34 ± 12.10 (18 – 60) years were divided into 2 equal groups. the 2 groups were in a similar condition regarding mean age (p = 0.168), sex distribution (p = 0.267), underlying disease (p = 0.414) and alcohol and drug abuse (p = 0.524). mean pain scores of the patients based on vas were not significantly different between the 2 groups on admission and 20, 30, 60, 120, and 180 minutes after drug administration. success rate in reducing the pain by at least 3 points on vas was equal and 91.1% for both groups on the 20t h minute and reached 100% on the 30t h minute for both groups. the number of cases that were pain-free on the 20t h minute was significantly higher in the morphine groups (31 versus 16 patients, p = 0.004). however, on the 30t h minute both groups experienced a similar condition in this regard (39 versus 29, p = 0.063). none of the patients in the 2 groups experienced the studied side effects. conclusion: it seems that mg sulfate, as a muscle relaxant agent, can be considered as a safe adjunct medication in controlling the pain of renal colic patients in the ed. keywords: magnesium sulfate; morphine; renal colic; pain management; emergency service, hospital cite this article as: majidi a, derakhshani f. intravenous magnesium sulfate for pain management in patients with acute renal colic; a randomized clinical trial. 2020; 8(1): e5. 1. introduction pain is one of the most common causes of patients visiting emergency departments (eds) and pain control is one of the important responsibilities of the specialists in this department (1). in the time interval from 2006 to 2009, there was an increase in the prevalence of renal colic from 289 to 305 cases for each 100000 population in the united states, part of which might be due to increased use of more accurate diagnostic tools such as computed tomography (ct) scan (2). choosing an efficient drug with easy administration, few side ∗corresponding author: fatemeh derakhshani; emergency department, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. tel: 00989111375820, email: dr.fatemeh.derakhshani62@gmail.com effects, and rapid acting in pain management of these patients, is of great interest. main drugs used in managing renal colic pain are categorized into 2 major groups of non-steroid anti-inflammatory drugs (nsaids) and opioids. it seems that tocolytic drugs such as magnesium (mg) sulfate can be helpful in decreasing the pain caused by the stone passing from the ureter by reducing ureter smooth muscle contractions. by preventing calcium from entering through the cell membrane of smooth muscles, mg sulfate can reduce calcium, which is required for muscle contraction (3, 4). in addition, by reducing acetyl choline in neural terminals mg sulfate can decrease muscle contractions (5). the role of mg sulfate in decreasing pains due to surgeries has been confirmed in various studies (6-8). the results of the study by delavar kasmaei et al. regarding comparison of mg sulfate and ketorolac in controlling mithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. majidi et al. 2 graine headaches were indicative of similar effects of both drugs in the acute phase and better performance of mg sulfate 1 hour and 2 hours after drug administration (9). additionally, jokar et al. have emphasized the role of mg sulfate as an adjunct medication in controlling renal colic and reducing the need for opioid drugs (10). mg sulfate has been found to be safe and effective in controlling neuropathic pains due to cancer (11). however, kothari et al. have estimated the power of mg sulfate to be lower than short-acting opioids (12). studies regarding effectiveness and safety of mg sulfate in controlling patients’ pain are still ongoing, especially in the ed. therefore, the present study has been designed and performed with the aim of assessing the role of mg sulfate in controlling the pain caused by renal colic in ed. 2. methods 2.1. study design and setting the present double blind randomized clinical trial was performed on patients with acute renal colic presenting to the ed of shohadaye tajrish hospital, tehran, iran, from march 2017 to march 2018. protocol of the study was approved by the ethics committee of shahid beheshti university of medical sciences under the number sbmu.msp.rec.1396.2548 and was registered on the iranian clinical trial registry under the number irct20171206037774n1. the researchers adhered to research ethics and confidentiality of patient data based on the recommendations of helsinki declaration. informed consent was obtained from the patients for participating in the study. 2.2. participants patients with acute renal colic in the age range of 18 – 60 years were studied without any sex limitation. patients with known arrhythmia or heart block; cardiac failure, myocardial injuries; kidney failure; hepatitis; cardiac glycoside recipients; those consuming alcohol, opioid drugs, anti-anxiety medications, barbitorates, anti-depressants, anti-psychotic and sleep medications, and calcium channel blockers; those affected with myasthenia gravis and other neuromuscular diseases; pregnant women or those suspected with pregnancy; those having underlying bradycardia (heart rate less than 60 /minute) and long qrs interval; patients who did not sign the consent form; and cases with sensitivity to morphine or mg sulfate were excluded from the study. in addition, those who had received any kind of analgesics or sedatives during the 6 hours prior to presentation to the ed were also excluded. 2.3. intervention after history taking and clinical examination, pain score of the patients was evaluated based on visual analogue scale (vas) and morphine sulfate with 0.1 mg/kg dose was intravenously injected for all the patients via the median cubital vein during 1 minute. if the pain persisted 10 minutes after receiving morphine with a pain score over 6 and considering the inclusion and exclusion criteria, patients were allocated to either intravenous (iv ) mg sulfate (2cc of 50% solution that was diluted with normal saline solution until reaching 100 ml injected during 15 minutes) or iv morphine (0.1 mg/kg dose) groups via block randomization using random numbers table. double dummy method was used for blinding, which means that recipients of injected morphine simultaneously received 100 ml normal saline and those receiving mg also received iv distilled water with the same volume and speed as morphine. the whole mentioned process was done under constant cardiac, respiratory and blood pressure monitoring and pulse oximetry under the supervision of the senior emergency medicine resident who was in charge of performing the study but was blind to the type of drug administered. considering the random method, injectable drugs were prepared in advance in syringes with the same color and with the same volume by a nurse who helped in performing the study and was blind to the pain severity and other characteristics of the patients on admission. pain severity of the patients was reevaluated and recorded 20, 30, 60, 120, and 180 minutes after drug administration. if the patients’ pain was not controlled after being allocated to a study group and receiving the allocated medication, patients received reminder doses of morphine and were excluded from the study, but they were included in the statistical analyses in order to adhere to the intention to treat method. 2.4. data gathering baseline characteristics of the patients, pain severity based on vas on admission and 20, 30, 60, 120, and 180 minutes after drug administration and probable side effects such as nausea, vomiting, vertigo, shortness of breath, allergy, and respiratory depression were gathered and recorded for all patients by the senior emergency medicine resident in charge of the patient and under supervision of the attending physician on duty using a pre-designed checklist. in this study, 3 or more points drop in the pain score based on vas was considered as treatment success. suspicion to renal colic was made by the senior resident in charge of the patient based on clinical symptoms including acute and sudden pain with a colic nature and its radiation to the groin or the lower part of the abdomen and also the testes with or without nausea, vomiting, sweating, paleness, burning urine, frequent urination, urinary urgency, and blood in urine, and was confirmed using ultrasonography or abdominal and pelvic computed tomography (ct) scan as well as urinalysis at the first possible opportunity that the patient could bear it. pain score was assessed using vas. this scale consists of a 10-cm ruler on which 0 indicates absence of pain and 10 indicates the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e5 figure 1: flowchart of the study. most severe pain possible. 2.5. outcomes the studied outcomes included success in pain management and probable side effects due to prescription of drugs. 2.6. statistical analysis for statistical analysis, spss software version 20 was used and for comparing the results between the 2 groups, t-test, mann-whitney, chi square, or fisher’s exact tests were applied. the findings were reported as mean and standard deviation (sd) or frequency and percentage. p value less than 0.05 was considered as level of significance. the person performing statistical analyses was also blind to the drugs received by the groups. 3. results 3.1. baseline characteristics of the studied patients finally, 90 patients with the mean age of 37.34 ± 12.10 (18 – 60) years were randomly allocated to one of the 2 groups receiving either mg sulfate (45 patients) or morphine sulfate (45 patients) (figure 1). table 1 has compared the clinical data of the studied groups. the 2 groups were in a similar condition regarding mean age (p = 0.168), sex distribution (p = 0.267), being affected with underlying illnesses (p = 0.414) and alcohol and drug abuse (p = 0.524). 3.2. outcomes table and figure 2 have compared pain severity between the 2 groups on admission to ed and at other times. mean pain this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. majidi et al. 4 figure 2: pain reduction trend in the groups receiving morphine and magnesium at different studied times. table 1: baseline characteristics of studied patients variables morphine (n = 45) mg sulfate (n = 45) p value age (year) mean ± sd 39.1 ± 13.2 35.6 ± 10.8 0.168 sex male 27 (60.0) 32 (71.1) 0.267 female 18 (40.0) 13 (28.9) drug abuse yes 27 (60.0) 17 (37.8) 0.414 no 18 (40.0) 28 (62.2) underlying illness yes 11 (24.4) 10 (22.2) 0.524 no 34 (75.5) 35 (77.7) vital signs (on admission) systolic bp (mmhg) 124.5 ± 12.3 122.3 ± 9.1 0.327 diastolic bp (mmhg) 82.3 ± 11.4 80.0 ± 6.5 0.254 heart rate (/minute) 75.1 ± 6.7 76.3 ± 4.0 0.320 respiratory rate (/minute) 12.4 ± 0.9 12.7 ± 1.6 0.130 o2 saturation (%) 94.3 ± 2.0 93.0 ± 12.0 0.457 data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure. score of the patients based on vas on admission and 20, 30, 60, 120, and 180 minutes after drug administration were not significantly different between the 2 groups. success rate in reducing the pain by at least 3 points on vas was equal for both groups on the 20th minute and was 91.1% (41 out of 45 patients in each group) and reached 100% on the 30th minute for both groups. the number of cases that were painfree (pain severity of 0) on the 20th minute was significantly higher in the morphine groups (31 versus 16 patients, p = 0.004). of course, on the 30th minute both groups experienced a similar condition in this regard (39 versus 29, p = 0.063). none of the patients in either group experienced any side effects including hypertension, allergy, drop in respiratory rate this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e5 table 2: comparing the pain score of the patients in the groups receiving morphine and magnesium (mg) sulfate at different studied times time morphine (n = 45) mg sulfate (n = 45) p value on admission 6.33±0.71 6.51±0.76 0.253 20t h minute 0.90±2.0 1.58±1.9 0.102 30t h minute 0.24±0.68 0.53±0.84 0.077 60t h minute 0.11±0.32 0.18±0.44 0.413 120t h minute 0.18±0.39 0.13±0.34 0.566 180t h minute 0.20±0.40 0.22±0.42 0.799 data are presented as mean ± standard deviation (sd). or reduced arterial blood oxygen saturation, and respiratory depression. 4. discussion based on the findings of the present study, mg sulfate showed a similar effect and an equal success rate in relieving the acute pain caused by renal colic in the patients presenting to ed when compared to morphine sulfate. however, it seems that the time interval to reach a pain-free status is a little longer for the group receiving mg sulfate. none of the patients in either group experienced side effects in the prescribed doses in this study. findings of the present study were similar to the results of jokar et al. study in 2016, which evaluated and compared mg sulfate with ketorolac in management of pain caused by renal colic and expressed that mg sulfate can reduce the pain of patients with renal colic and decrease the need for additional morphine (10). kocman et al. found that injection of a low dose of mg sulfate significantly reduced the pain following surgery in patients that underwent laparoscopic cholecystectomy (13). mg sulfate has been identified as a safe and efficient drug in dilation of the bronchi in patients with severe asthma (14). mg sulfate leads to loosening of the smooth muscles in the bronchial walls and therefore, dilation of their airways, a mechanism that may also be true regarding the smooth muscles of the ureter. in a study, rezae et al. evaluated the effect of mg sulfate injection on pain relief following cesarean section and stated that injection of 50 mg/kg mg sulfate leads to pain reduction and lowers the need for other analgesic drugs (15). on the other hand, a study carried out on women giving birth via cesarean section showed that intraspinal injection of 5% bupivacaine and mg sulfate did not have much effect on elongation of analgesia. however, iv injection of mg sulfate along with intraspinal injection of 5% bupivacaine showed better results (16). in the present study, adding mg sulfate to the standard treatment of patients with acute renal colic led to a decrease in pain severity and reduced need for additional morphine. in the future, mg sulfate might be considered for establishing pain control protocols and sedation induction in patients with acute renal colic in the ed. however, we should not forget that prescription of mg sulfate is very dose-dependent; therefore, choosing the proper dose is very important for maximum efficiency and minimum toxicity. on the other hand, mg sulfate should not be used in patients with known cardiac block, myocardial injury, severe kidney failure, hepatitis, and addison’s disease and it is not recommended for use in patients with decreased kidney function, those who receive cardiac glycosides, patients with myasthenia gravis and other neuromuscular diseases, and when giving birth. yet, in cases that there is an acute pain not responding to available medications or they are banned for use or are not available in ed, we might be able to consider mg sulfate as a proper alternative with few side effects. considering the obtained results and not seeing any significant side effect when using mg sulfate drug as well as its easy administration, and on the other hand the problems caused by prescribing opioids, mg sulfate can be used for adjunct treatment of patients with acute renal colic in ed to decrease patients’ pain severity. in addition, through simultaneous use of mg sulfate, the rate of administration of other opioid drugs and their possible side effects can also be reduced. 5. limitation not homogenizing patients regarding size and location of stone could be counted as a limitation of the present study. in addition, by increasing sample size, various subgroup analyses based on sex or drug and alcohol abuse and etc. can be performed. 6. conclusion based on the findings of the present study, mg sulfate showed a similar effect and an equal success rate in relieving the acute pain caused by renal colic in the patients presenting to ed when compared to morphine sulfate. however, it seems that the time interval to reach a pain-free status is a little longer for the group receiving mg sulfate. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. majidi et al. 6 7. declarations 7.1. acknowledgements all staff members who helped perform the trial are acknowledged. 7.2. author contribution all the authors met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. authors orcids alireza majidi: 0000-0002-8732-140x 7.3. funding/support no funds have been received for doing this project. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. todd kh, ducharme j, choiniere m, crandall cs, fosnocht de, homel p, et al. pain in the emergency department: results of the pain and emergency medicine initiative (pemi) multicenter study. the journal of pain. 2007;8(6):460-6. 2. ghani kr, roghmann f, sammon jd, trudeau v, sukumar s, rahbar h, et al. emergency department visits in the united states for upper urinary tract stones: trends in hospitalization and charges. the journal of urology. 2014;191(1):90-6. 3. gourgoulianis k, chatziparasidis g, chatziefthimiou a, molyvdas p-a. magnesium as a relaxing factor of airway smooth muscles. journal of aerosol medicine. 2001;14(3):301-7. 4. sontia b, touyz rm. role of magnesium in hypertension. archives of biochemistry and biophysics. 2007;458(1):339. 5. wang h, liang q-s, cheng l-r, li x-h, fu w, dai w-t, et al. magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle-type nicotinic acetylcholine receptor in vitro. acta pharmacologica sinica. 2011;32(12):1454. 6. levaux c, bonhomme v, dewandre p-y, brichant j-f, hans p. effect of intra-operative magnesium sulphate on pain relief and patient comfort after major lumbar orthopaedic surgery. anaesthesia. 2003;58(2):131-5. 7. ozcan pe, tugrul s, senturk nm, uludag e, cakar n, telci l, et al. role of magnesium sulfate in postoperative pain management for patients undergoing thoracotomy. journal of cardiothoracic and vascular anesthesia. 2007;21(6):827-31. 8. bolcal c, iyem h, sargin m, mataraci i, yildirim v, doganci s, et al. comparison of magnesium sulfate with opioid and nsaids on postoperative pain management after coronary artery bypass surgery. journal of cardiothoracic and vascular anesthesia. 2005;19(6):714-8. 9. delavar kasmaei h, amiri m, negida a, hajimollarabi s, mahdavi n. ketorolac versus magnesium sulfate in migraine headache pain management; a preliminary study. emergency (tehran, iran). 2017;5(1):e2. 10. jokar a, cyrus a, babaei m, taheri m, almasi-hashiani a, behzadinia e, et al. the effect of magnesium sulfate on renal colic pain relief; a randomized clinical trial. 2016. 2016;5(1):e25. 11. crosby v, wilcock a, mrcp d, corcoran r. the safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer. journal of pain and symptom management. 2000;19(1):35-9. 12. kothari d, mehrotra a, choudhary b, mehra a. effect of intravenous magnesium sulfate and fentanyl citrate on circulatory changes during anaesthesia and surgery: a clinical study. indian journal of anaesthesia. 2008;52(6):800. 13. bacak-kocman i, krobot r, premuzic j, kocman i, stare r, katalinic l, et al. the effect of preemptive intravenous low-dose magnesium sulfate on early postop erative pain after laparoscopic cholecystectomy. acta clinica croatica. 2013;52(3):289. 14. rowe bh, bretzlaff ja, bourdon c, bota gw, camargo jr ca. intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature. annals of emergency medicine. 2000;36(3):181-90. 15. rezae m, naghibi k, taefnia am. effect of pre-emptive magnesium sulfate infusion on the post-operative pain relief after elective cesarean section. advanced biomedical research. 2014;3. 16. unlugenc h, ozalevli m, gunduz m, gunasti s, urunsak i, guler t, et al. comparison of intrathecal magnesium, fentanyl, or placebo combined with bupivacaine 0.5% for parturients undergoing elective cesarean delivery. acta anaesthesiologica scandinavica. 2009;53(3):346-53. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e83 le t t e r to ed i to r superinfection by trichomonas, a second reason to add metronidazole to covid-19 treatment; a letter to editor christophe duboucher1∗ 1. laboratory of pathology, c.h.i. de poissy / saint-germain, saint-germain-en-laye, france. received: september 2020; accepted: september 2020; published online: 22 october 2020 cite this article as: duboucher c. superinfection by trichomonas, a second reason to add metronidazole to covid-19 treatment; a letter to editor. arch acad emerg med. 2020; 8(1): e83. dear editor, all countries are struggling against the covid-19 pandemic. one million deaths have been recorded. acute respiratory distress syndrome (ards) is the major complication. no antiviral therapy has been shown to be clearly effective for reducing the rate of mortality in published randomised controlled trials. in an article published in the last issue of archives of academic emergency medicine, metronidazole is suggested to be tested in clinical trials (1). in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines. it could also decrease neutrophilgenerated reactive oxygen species, and thus could counteract majority of the immunopathological manifestations of the covid-19 infection. metronidazole could be included in clinical trials for another reason. more than ten years ago we observed that lungs of patients diseased from ards, show superimposed infection by trichomonads (2). in this situation, local hypoxic conditions could be the main factor favoring trichomonad infection development as alveolar lumens are obliterated by fibrin and cellular debris. if our observations show that trichomonads infection could develop during the late phase of ards, the deleterious action of trichomonads remains to be proven. nevertheless, amoeboid transformation argues for aggressiveness of trichomonads (3). when facing the current covid-19 pandemic, the major medical complication of which is ards, the presence of trichomonads should not be overlooked or considered an anecdotal event. it seems fair to assess the potential deleterious role of trichomonads in prospective clinical trials. the same observation of superimposed infection by tri∗corresponding author: christophe duboucher; 29 rue raymond queneau, 92500 rueil malmaison, france. phone: +33.6.86.32.42.31, fax: +33.9.57.39.78.12, email: christophe.duboucher@trichomoniasispathology.org chomonads has been made during the course of pneumocystis jirovecii pneumonia (pjp) (4). however, since our publication in 2005, observations of trichomonads in the course of pjp and of ards have not been made or commented on by other cytopathologists or parasitologists. readers who are not observers may have doubts, but observers may see these unidentified cells in bronchoalveolar lavage fluids (balf), and worry about their nature. nevertheless, there is an explanation for this occultation. in alveolar lumens, when adhering to epithelial cells of host, trichomonads evolve from a flagellated form to an amoeboid form. when transforming into amoeboid form, they develop pseudopods and lose their flagella. thus, they look like anonymous cells that have lost their distinctive marks and can mimic human cells. so, on slides colored using mgg, amoeboid trichomonads do not harbor a familiar appearance neither for parasitologists nor for cytopathologists. it is difficult to find reports in the literature before 2005, when the word "trichomonad" was not used as keyword of indexation. the unique article we found, in which these "alien cells" are presented, was published in 2001 in acta cytologica by jan jacobs et al. (5). the authors described "non-identified cells" almost exclusively in balf from human immunodeficiency virus (hiv )-infected patients. unfortunately, the authors failed to ask themselves the following question: "are these cells human cells?". parasitologists and cyto-pathologists need to be convinced by pictures. microphotographs from different cases of ards and pjp are visible at https://www.trichomoniasis-pathology.org/ 1. declarations 1.1. acknowledgements none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. duboucher 2 1.2. conflict of interest none. 1.3. funding and support no financial support has been received. references 1. gharebaghi r, heidary f, moradi m, parvizi m. metronidazole; a potential novel addition to the covid-19 treatment regimen. archives of academic emergency medicine. 2020;8(1). 2. duboucher c, barbier c, beltramini a, rona m, ricome jl, morel g, et al. pulmonary superinfection by trichomonads in the course of acute respiratory distress syndrome. lung. 2007;185(5):295-301. 3. duboucher c, caby s, pierce rj, capron m, deicas e, viscogliosi e. trichomonads as superinfecting agents in pneumocystis pneumonia and acute respiratory distress syndrome. journal of eukaryotic microbiology. 2006;53:s95-s7. 4. duboucher c, gerbod d, noel c, durand-joly i, delgadoviscogliosi p, leclerc c, et al. frequency of trichomonads as coinfecting agents in pneumocystis pneumonia. acta cytologica. 2005;49(3):273-7. 5. jacobs ja, dieleman mm, cornelissen e, groen e, wagenaar ss, drent m. bronchoalveolar lavage fluid cytology in patients with pneumocystis carinii pneumonia. acta cytologica. 2001;45(3):317. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2020; 8(1): e52 co m m e n ta ry pulmonary thromboembolism as a potential cause of clinical deterioration in covid-19 patients; a commentary saeed safari1,2, mehdi mehrani3, mahmoud yousefifard4∗ 1. proteomics research center, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. tehran heart center, tehran university of medical science, tehran, iran. 4. physiology research center, iran university of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 19 april 2020 abstract: although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging, reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence. physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire. this letter aimed to draw attention to the role of pulmonary thromboembolism as a potential and possible cause of clinical deterioration in covid-19 patients. keywords: covid-19; embolism and thrombosis; clinical deterioration; computed tomography angiography; platelet aggregation inhibitors cite this article as: safari s, mehrani m, yousefifard m. pulmonary thromboembolism as a potential cause of clinical deterioration in covid-19 patients; a commentary. arch acad emerg med. 2020; 8(1): e52. dear editor: more than three months has passed from identification of the first case of pneumonia due to sars-cov-2 virus in china and it has subsequently spread to countries around the world. with publication of clinical, imaging, and laboratory findings of covid-19 patients, our information on the behavior of the virus in the human body has increased. although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging (1), reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence (2, 3). for example, a study on more than 1000 patients with covid-19 in china has shown that about 18% of non-severe cases and 3% of severe cases had no abnormal finding in radiography and computed tomography (ct) scan (4). in addition, significant and notable reports among the lab∗corresponding author: mahmood yousefifard; physiology research center, school of medicine, iran university of medical sciences, hemmat highway, tehran, iran; email: yousefifard.m@iums.ac.ir; tel: +982186704771 oratory findings include thrombocytopenia, disturbances in coagulation profile [prothrombin time (pt), partial thromboplastin time (ptt)], increase in d-dimer, and fibrin/fibrinogen degradation products (fdp). in a study on 94 patients, whose covid-19 was confirmed using rt-pcr, huan han et al. showed that the serum levels of d-dimer, fdp, and fibrinogen (fib) in these patients were higher than healthy individuals. they showed that d-dimer and fdp levels significantly and directly correlated with the severity of the disease and suggested d-dimer and fdp monitoring for early detection of severe cases (5). another study in china, which had evaluated about 300 patients, reported increased d-dimer levels in more than 35% of the studied patients. based on the findings of this study, ddimer levels were significantly higher in patients with more severe presentation of the disease (0.96 versus 0.35 mg/l; p < 0.001) (6). findings of a study in suzhou, china, has shown that fibrinogen level has increased in more than 65% of those with pneumonia due to covid-19 and the interesting part is that at the level of 4.8 gr/l, the sensitivity of fibrinogen in differentiation of severe patients has been reported to be 100% (7). by studying 192 patients with covid-19, zhou et al. inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. safari et al. 2 troduced d-dimer levels over 1 µg/ml as a predictor of poor outcome, which can aid physicians in detecting more severe patients in the initial stages (8). in addition to the mentioned findings, physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire (9). putting all the pieces of this puzzle together (thrombocytopenia, high serum d-dimer, inconsistency between clinical and imaging findings, and clinical deterioration of patients) a possible explanation for the afore-mentioned cases, from a clinical point of view, might be the formation of thrombosis. in this regard, a study revealed that ct angiography results of 25 patients with d-dimer levels higher than 6 îijg/ml in china indicated pulmonary embolism in ten (40%) patients (10). in this study, the emboli were found to be centralized in the small branches of pulmonary artery. additionally, using ct angiography, yuanliang xie et al. confirmed and reported the presence of pulmonary embolism in two covid-19 patients who had deteriorated (11). histopathologic findings of pulmonary biopsy of critical patients with covid-19 pneumonia indicated small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion, and micro-thrombosis formation. the blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes, which could be additional evidence for confirmation of this hypothesis (12, 13). a study on confirmed covid-19 cases admitted to icu reported a 31% prevalence of vascular thrombosis, which was most frequently (81%) seen in pulmonary vessels (14). it should be noted that micro-emboli are generally undetectable in ct angiography. therefore, worsening of respiratory condition in hospitalized patients should raise high suspicion to thrombosis formation as a potential cause of clinical deterioration. as a preliminary suggestion, it might be better to strongly consider performing pulmonary ct angiography for patients with disturbances in coagulation parameters, high d-dimer, pleuritic chest pain (reported in about 2% of patients) (15), inconsistency of dyspnea with imaging findings, as well as those whose clinical symptoms worsen and deteriorate during treatment. we should also add anticoagulant agents to the treatment cocktail of high-risk patients such as old, obese, pregnant, and intubated cases, as well as those with other risk factors of thromboembolism. 1. declarations 1.1. acknowledgment none. 1.2. authors contributions all the authors met the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids saeed safari: 0000-0002-7407-1739 mahmoud yousefifard: 0000-0001-5181-4985 1.3. role of the funding source not applicable. 1.4. conflict of interest the authors declare that there is no conflict of interest. references 1. wu j, wu x, zeng w, guo d, fang z, chen l, et al. chest ct findings in patients with corona virus disease 2019 and its relationship with clinical features. invest radiol. 2020;55(5):257-61. 2. bernheim a, mei x, huang m, yang y, fayad za, zhang n, et al. chest ct findings in coronavirus disease-19 (covid-19): relationship to duration of infection. radiology. 2020:[in press]. 3. ai t, yang z, hou h, zhan c, chen c, lv w, et al. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases. radiology. 2020:200642. 4. guan w-j, ni z-y, hu y, liang w-h, ou c-q, he j-x, et al. clinical characteristics of coronavirus disease 2019 in china. new england journal of medicine. 2020:[in press]. 5. han h, yang l, liu r, liu f, wu k-l, li j, et al. prominent changes in blood coagulation of patients with sars-cov2 infection. clin chem lab med. 2020:[in press]. 6. cai q, huang d, ou p, yu h, zhu z, xia z, et al. covid19 in a designated infectious diseases hospitaloutside hubei province,china. allergy. 2020:[in press]. 7. wang y, yao l, zhang j-p, tang p-j, ye z-j, shen x-h, et al. clinical characteristics and laboratory indicator analysis of 69 covid-19 pneumonia patients in suzhou, china. lancet. 2020:[pre-print]. 8. zhou f, yu t, du r, fan g, liu y, liu z, et al. clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. lancet. 2020;395:1054-62. 9. xu z, shi l, wang y, zhang j, huang l, zhang c, et al. pathological findings of covid-19 associated with acute respiratory distress syndrome. lancet respir med. 2020;8(4):420-2. 10. chen j, wang x, zhang s, liu b, wu x, wang y, et al. findings of acute pulmonary embolism in covid-19 pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e52 tients. ssrn. 2020:[preprint]. 11. xie y, wang x, yang p, zhang s. covid-19 complicated by acute pulmonary embolism. radiology: cardiothoracic imaging. 2020;2(2):e200067. 12. luo w, yu h, gou j, li x, sun y, li j, et al. clinical pathology of critical patient with novel coronavirus pneumonia (covid-19). 2020:[preprint]. 13. yao x, li t, he z, ping y, liu h, yu s, et al. a pathological report of three covid-19 cases by minimally invasive autopsies. chinese j pathol. 2020;49:e009. 14. klok fa, kruip mjha, van der meer njm, arbous ms, gommers dampj, kant km, et al. incidence of thrombotic complications in critically ill icu patients with covid-19. thrombosis research. 2020. 15. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. lancet. 2020;395(10223):507-13. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references emergency. 2018; 6 (1): e21 or i g i n a l re s e a rc h the effect of low-dose ketamine in treating acute asthma attack; a randomized clinical trial mehrdad esmailian1, mahboubeh koushkian esfahani1∗, farhad heydari1 1. emergency medicine research center, al-zahra research institute, isfahan university of medical sciences, isfahan, iran. received: march 2018; accepted: april 2018; published online: 10 april 2018 abstract: introduction: efficient treatment of asthma can play an important role in controlling asthma attacks, rapid recovery and decrease of patient mortality. therefore, in the present study the therapeutic effect of low-dose ketamine is evaluated in patients with acute asthma attack. methods: in the present single-blind, randomized clinical trial with placebo control, the effect of low-dose intravenous ketamine in treating 18 to 85 year-old asthmatic patients who presented to the emergency department was evaluated. peak expiratory flow rate (pefr) and the patients’ response to treatment were measured before and 1 hour after treatment. additionally, using spss 22.0, effectiveness of ketamine with 0.3, 0.4, and 0.5 mg/kg doses followed by infusion of the same dose during 30 minutes were compared with placebo. results: 92 patients were enrolled (59.8% female, mean age 48.5 ± 13.9 years). 15 (16.3%) patients were treated with 0.3 mg/kg ketamine, 14 (15.2%) with 0.4 mg/kg, and 16 (17.4%) with 0.5 mg/kg doses. mean pefr was 336.2 ± 101.5 liters in the placebo group and 345.8 ± 84.7 liters in the ketamine group before intervention (p = 0.6), while after intervention, they were 352.1 ± 101.2 and 415.8 ± 76.2 liters, respectively (p = 0.001). ketamine treatment with 0.4 and 0.5 mg/kg doses led to a higher increase in pefr compared to 0.3mg/kg dose (df: 3, 88; f = 23.8; p < 0.001). conclusion: it seems that administration of 0.4 0.5 mg/kg doses of intravenous ketamine followed by infusion of the same dose during 30 minutes can be effective for rapid recovery of pefr in patients with mild to moderate asthma. keywords: ketamine; asthma; efficiency; peak expiratory flow rate; emergency service, hospital © copyright (2018) shahid beheshti university of medical sciences cite this article as: esmailian m, koushkian esfahani m, heydari f. the effect of low-dose ketamine in treating acute asthma attack; a randomized clinical trial. emergency. 2018; 6(1): e21. 1. introduction a sthma is a diffused obstruction of airways that may present as shortness of breath, wheezing, and coughing. it is one of the most common chronic illnesses, which presently affects 300 million people all over the world and this number is predicted to rise to 100 million in 2025 (1). in iran, the average prevalence of this disease in the under 18-year-old population is estimated to be 13.4% (2). clinical symptoms of asthma are relieved spontaneously or using drugs. comprehensive research has been done on control and treatment of asthma and standard treatments have been developed. yet, a high percentage of patients do not respond well to the treatments and might experience severe attacks and dangerous complications such as hypoxia, respira∗corresponding author: mahboubeh koushkian esfahani; department of emergency medicine, al-zahra hospital, soffeh blvd, isfahan, iran. tel: 00989133266313 email: kushkian.m@gmail.com tory arrest, and mortality. a bunch of controlling or preventive drugs such as steroids, inhaled beta agonists and anticholinergics, and short-acting theophylline are suggested for management of the patients (3). ketamine is a well-known drug with safe and predictable sedative, analgesic, and antiemetic effects. the half-life of this drug is 2-4 hours and it is rapidly absorbed, crosses blood-brain barrier, and exerts its effect on central nervous system (cns) (5). it is also a bronchodilator, and using a 1-2 mg/kg dose of it has been approved as an inductive agent in rapid sequence intubation (rsi) of asthma patients (4). it protects airways and respiratory reflexes without any disturbances to the cardiovascular system. therefore, it may be prescribed in emergency departments with limited monitoring devices. the important thing about this drug is that in doses lower than 1mg/kg it does not have sedative effects, while in higher doses it can cause side effects such as apnea and laryngospasm. these side effects can be severe in 1-2% of patients and are very dose-dependent and more probable in higher doses and inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. esmailian et al. 2 travenous (iv ) prescription (6). using 1-2 mg/kg iv doses followed by 2-3 mg/kg iv infusion has been able to delay the need for intubation in pediatric asthma attack (7). introducing new ways for controlling asthma attack with the aim of rapid recovery, decreasing cost, and discharging patients from emergency department seems necessary from therapeutic and logistic viewpoints. therefore, the present study aims to evaluate the effect of low-dose ketamine in treatment of patients with acute asthma attack. 2. methods 2.1. study design and setting the present study is a single blind, randomized clinical trial with placebo control that evaluates the effect of low-dose ketamine in treating asthmatic patients who presented to the emergency department of al-zahra teaching hospital, isfahan, iran, during january to august 2016. informed written consent was obtained from all patients included in the study. in addition, the present study was approved by the ethics committee of isfahan university of medical sciences. the researchers adhered to the principles of helsinki declaration and patient data confidentiality. this study has been registered on iranian registry of clinical trials (irct) under the number irct2015102912072n9. 2.2. participants patients with mild to moderate asthma (table 1), aged between 18 to 85 years old, without any prohibition for using iv ketamine and history of allergic reaction, were included. if the patient’s clinical condition worsened during the study, or needed ventilator support for respiration or showed ketamine side effects, he/she would be excluded. non-randomized, convenience sampling was done and patients were randomly allocated to intervention (iv ketamine) and control (placebo) groups using block randomization. 2.3. intervention: all patients underwent pulse oximetry and constant monitoring of arterial oxygen saturation, as well as oxygen therapy if needed. both groups received basic treatments of asthma attack with standard doses including inhaled beta agonists and anticholinergics, and iv corticosteroids. the intervention group received iv ketamine with 0.3, 0.4, or 0.5 mg/kg doses in addition to the standard treatment. since ketamine is colorless and odorless and its appearance is like water, distilled water was used as placebo for the control group. iv ketamine vials were 10 cc in volume with 50 mg/cc concentration (made by rotexmedica company, germany). at the time of use, drug was drawn in a syringe based on the patient’s weight and the volume was then set to 5 cc using distilled water. its injection was done during 1-2 minutes in a peripheral vein. subsequently, the same dose was infused during 30 minutes. peak expiratory flow rate (pefr) was measured and recorded before and 1 hour after treatment for all patients. the method for determining pefr was as follows: first, the device was set at 0, then it was held in a horizontal state and the patient was asked to hold the device’s pipe, which was washed and disinfected before, with their lips in a manner that air could only pass through the pipe. they were then asked to forcefully blow their expiratory flow into the peak flow meter (sibel, spain) after a deep inhalation. finally, the indicator would show a number representing the peak expiratory flow. the peak expiratory flow for each patient was then compared to their expected natural flow based on their sex, age, and height, and if it was lower than 70% of the normal rate, the case was considered as acute asthma attack. the peak flow meter number was read and reported by one person, for all patients. response to treatment was determined based on pefr an hour after treatment initiation and was rated as good (pefr > 70%), partial (40% < pefr < 69%), and poor (pefr < 40%) (table1). 2.4. data gathering a senior emergency medicine resident was responsible for data gathering using a check list that consisted of demographic data (sex, age), possible side effects of ketamine, and pefr of patients before and 1 hour after intervention. 2.5. statistical analysis the sample size calculated for this study was 60 cases considering zα =1.96, zβ = 0.84, s = 59, d = 30. data were entered to spss 22.0. after making sure data distribution was normal using kolmogorov–smirnov test (p = 0.62), they were presented as mean and standard deviation for quantitative data and frequency and percentage for qualitative data. independent t-test was used for comparison of pefr between the ketamine and placebo groups. in addition, to evaluate the efficiency of various ketamine doses (0.3, 0.4, 0.5 mg/kg) one-way anova was used. in all tests, p < 0.05 was considered significant. 3. results 92 patients were enrolled (59.8% female, mean age 48.5 ± 13.9 years). 47 (51.1%) of the patients were in the placebo group and 45 (48.9%) in the ketamine group. 15 (16.3%) patients were treated with 0.3 mg/kg ketamine, 14 (15.2%) with 0.4 mg/kg, and 16 (17.4%) with 0.5 mg/kg doses. age distribution between the studied groups was not significantly different (p = 0.09) but sex distribution significantly differed (p = 0.01). since patient’s sex is entered in the formula for calculation of pefr, this difference in distribution is adjusted for the analyses. mean pefr was 336.2 ± 101.5 liters in the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e21 table 1: definitions and measurement pefr * pefr was measured using a peak flow meter and the normal rate varies a little based on sex, age, and height of the patient asthma attack acute attack: pefr < 70% mild to moderate attack: 40% < pefr < 69% severe attack: pefr < 40% response to treatment good response: pefr > 70% partial response: 40% < pefr < 69% poor response: pefr < 40% apnea oxygen saturation dropping to < 85% for at least 3 seconds or decrease in respiratory rate to < 8 /minute *: peak expiratory flow rate. table 2: comparing mean change in peak expiratory flow rate (pefr) in different groups group pefr change p* before after placebo 336.2 ± 101.5 352.1 ± 101.2 16.0 ± 30.5 ref 0.3 mg/kg ketamine 325.3 ± 48.1 367.3 ± 56.9 42.0 ± 23.0 0.17 0.4 mg/kg ketamine 396.4 ± 89.4 443.6 ± 67.9 52.9 ± 45.0 0.02 0.5 mg/kg ketamine 320.6 ± 91.9 431.9 ± 80.2 111.3 ± 62.8 < 0.001 *, significance level has been reported based on comparison with the placebo group. data were presented as mean ± standard deviation. placebo group and 345.8 ± 84.7 liters in the ketamine group before intervention (p = 0.6), while after intervention, they were 352.1 ± 101.2 and 415.8 ± 76.2 liters, respectively (p = 0.001). treatment with low-dose ketamine has significantly increased pefr compared to placebo (p < 0.0001). pefr before intervention was not significantly different between the placebo group and different ketamine dose groups (df: 3, 88; f = 2.2; p = 0.1). however, ketamine treatment with 0.4 mg/kg (p = 0.02) and 0.5 mg/kg (p < 0.001) doses led to a significant increase in pefr compared to placebo. pefr changes in the 0.3 mg/kg dose group did not differ from the placebo group (df: 3, 88; f = 23.8; p = 0.17) (table 2). side effects of ketamine were not observed in any of the patients. 4. discussion the findings of the present study reveal that treatment of asthma with low-dose ketamine increases pefr. this rise is significant in 0.4 and 0.5 mg/kg doses. 0.5 mg/kg dose had higher efficiency compared to the 0.4 mg/kg dose. as we have mentioned before, asthma is one of the most common chronic illnesses all over the world. based on the involvement of the area, symptoms vary between a wheezing sound to airway obstruction. severe asthma can lead to respiratory deficiency and need for ventilator. inhaled corticosteroids are among the drugs suggested for asthma treatment in children and adults (8-11). to open the bronchial airways in asthmatic patients, ketamine may also be helpful. the first effective use of this drug in relieving pediatric asthma has been reported about 30 years ago (12). in various studies, ketamine has been suggested as an inductive agent for endotracheal intubation in asthma patients due to its benefits for bronchial airway stabilization. its serial injection will provide better results (4, 13-17). ketamine increases respiratory rate and subsequently, oxygen pressure, and decreases co2 pressure, which leads to asthma symptom relief (18). its most important probable side effects include hallucination, agitation, apnea, and laryngospasm (6). in a study by huber et al., after ketamine prescription a two third increase in airway stability was reported (19). in a study to evaluate the effectiveness of ketamine in symptom relief and pediatric asthma indices, 1 mg/kg dose of ketamine on admission and 0.75 mg/kg dose during the first hour were intravenously administered and the patients’ vital signs, pefr, and clinical asthma score were evaluated. the results showed that in all the afore-mentioned indices, after iv ketamine administration, asthma symptoms were relieved (17). in a clinical trial by howton et al. iv administration of low-dose ketamine with 0.2 mg/kg dose and repeated injection of 0.5 mg/kg dose 3 times per hour in patients over 18 years old, had a significant effect on respiratory rate, respiratory flow, and berg’s score of asthmatic patients compared to the placebo group. while in a similar study with the same initial dose and twice a day injection with 0.5 mg/kg dose, asthmatic children’s condition did not significantly improve (20). the effect of lowdose ketamine in adults who were not ventilator-dependent showed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. esmailian et al. 4 that this drug is generally effective for relieving bronchial airway spasms and increasing blood oxygen saturation, although in some cases it will be accompanied by side effects such as hallucination, agitation and increase in pulmonary secretions (16). some have reported ketamine to be the drug that makes asthmatic children independent of mechanical ventilators (7). based on the findings of this study, it seems that administration of 0.4 and 0.5 mg/kg doses of ketamine can have beneficial effects in asthma symptom relief compared to the placebo group. 5. limitation the present study had some limitations such as small number of patients in each group of ketamine doses, which makes interpretation and generalization of the results difficult. further study on the subject with a larger number of participants and more accurate methodology is suggested to make the findings more generalizable. 6. conclusion it seems that administration of 0.4 0.5 mg/kg doses of iv ketamine followed by infusion of the same dose during 30 minutes can be effective for rapid recovery of pefr in mild to moderate asthma patients. 7. appendix 7.1. acknowledgements none. 7.2. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict. references 1. masoli m, fabian d, holt s, beasley r. the global burden of asthma: executive summary of the gina dissemination committee report. allergy. 2004;59(5):469-78. 2. heidarnia ma, entezari a, moein m, mehrabi y, pourpak z. prevalence of asthma symptom in iran: a metaanalysis. pejouhesh. 2007;31(3):217-25. 3. fazlollahi m, moein m. national guidelines for asthma. tehran, iran: ministry of health and medical education, deputy of health. center for non-communicable diseases control, national committee of asthema. 2009. 4. l’hommedieu cs, arens j. the use of ketamine for the emergency intubation of patients with status asthmaticus. annals of emergency medicine. 1987;16(5):568-71. 5. cromhout a. ketamine: its use in the emergency department. emergency medicine. 2003;15(2):155-9. 6. wai a. roberts and hedges: clinical procedures in emergency medicine. lww; 2010. 7. denmark tk, crane ha, brown l. ketamine to avoid mechanical ventilation in severe pediatric asthma. the journal of emergency medicine. 2006;30(2):163-6. 8. adams n, jones p. the dose–response characteristics of inhaled corticosteroids when used to treat asthma: an overview of cochrane systematic reviews. respiratory medicine. 2006;100(8):1297-306. 9. dahl r, engelstatter r, trebas-pietras e, kuna p. a 24week comparison of low-dose ciclesonide and fluticasone propionate in mild to moderate asthma. respiratory medicine. 2010;104(8):1121-30. 10. buston km, wood sf. non-compliance amongst adolescents with asthma: listening to what they tell us about self-management. family practice. 2000;17(2):134-8. 11. lasserson tj, cates cj, lasserson eh, white j. fluticasone versus’ extrafine’hfa-beclomethasone dipropionate for chronic asthma in adults and children. the cochrane library. 2006. 12. betts ek, parkin ce. use of ketamine in an asthmatic child: a case report. anesthesia & analgesia. 1971;50(3):420-1. 13. corssen g, gutierrez j, reves jg, huber jr fc. ketamine in the anesthetic management of asthmatic patients. anesthesia & analgesia. 1972;51(4):588-94. 14. nettles dc, herrin tj, mullen jg. ketamine induction in poor-risk patients. anesthesia & analgesia. 1973;52(1):59-64. 15. rees di, howell ml. ketamine-atracurium by continuous infusion as the sole anesthetic for pulmonary surgery. anesthesia & analgesia. 1986;65(8):860-4. 16. lau tt, zed pj. does ketamine have a role in managing severe exacerbation of asthma in adults? pharmacotherapy: the journal of human pharmacology and drug therapy. 2001;21(9):1100-6. 17. petrillo t, petrillo tm, fortenberry jd, linzer jf, simon hk. emergency department use of ketamine in pediatric status asthmaticus*. journal of asthma. 2001;38(8):65764. 18. strube p, hallam p. ketamine by continuous infusion in status asthmaticus. anaesthesia. 1986;41(10):1017-9. 19. huber jr f, gutierrez j, corssen g. ketamine: its effect on airway resistance in man. southern medical journal. 1972;65(10):1176-80. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e21 20. howton jc, rose j, duffy s, zoltanski t, levitt ma. randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. annals of emergency medicine. 1996;27(2):170-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e57 or i g i n a l re s e a rc h correlation between chest computed tomography scan findings and mortality of covid-19 cases; a cross sectional study masoomeh raoufi1, seyed amir ahmad safavi naini2, zahra azizan2, fatemeh jafar zade2, fatemeh shojaeian2, masoud ghanbari boroujeni2, farzaneh robatjazi3, mehrdad haghighi4, ali arhami dolatabadi5, hossein soleimantabar1, simindokht shoaee4, hamidreza hatamabadi5∗ 1. department of radiology, school of medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. imam hossein clinical research development center, imam hossein hospital, shahid beheshti university of medical science, tehran, iran. 3. department of radiology, school of medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 4. department of infectious diseases, imam hossein teaching and medical hospital, shahid beheshti university of medical sciences, tehran, iran. 5. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. received: may 2020; accepted: may 2020; published online: 14 may 2020 abstract: introduction: predicting the outcomes of covid-19 cases using different clinical, laboratory, and imaging parameters is one of the most interesting fields of research in this regard. this study aimed to evaluate the correlation between chest computed tomography (ct) scan findings and outcomes of covid-19 cases. methods: this cross sectional study was carried out on confirmed covid-19 cases with clinical manifestations and chest ct scan findings based on iran’s national guidelines for defining covid-19. baseline and chest ct scan characteristics of patients were investigated and their correlation with mortality was analyzed and reported using spss 21.0. results: 380 patients with the mean age of 53.62 ± 16.66 years were evaluated (66.1% male). the most frequent chest ct scan abnormalities were in peripheral (86.6%) and peribronchovascular interstitium (34.6%), with ground glass pattern (54.1%), and round (53.6%) or linear (46.7%) shape. there was a significant correlation between shape of abnormalities (p = 0.003), ct scan severity score (ctss) (p <0.0001), and pulmonary artery ct diameter (p = 0. 01) with mortality. the mean ctss of non-survived cases was significantly higher (13.68 ± 4.59 versus 8.72 ± 4.42; <0.0001). the area under the receiver operating characteristic (roc) curve of ctss in predicting the patients’ mortality was 0.800 (95% ci: 0.716-0.884). the best cut off point of chest ctss in this regard was 12 with 75.82% (95% ci: 56.07%-88.98%) sensitivity and 75.78% (95% ci: 70.88%-80.10%) specificity. the mean main pulmonary artery diameter in patients with ctss ≥ 12 was higher than cases with ctss < 12 (27.89 ± 3.73 vs 26.24 ± 3.14 mm; p < 0.0001). conclusion: based on the results of the present study it seems that there is a significant correlation between chest ct scan characteristics and mortality of covid-19 cases. patients with lower ctss, lower pulmonary artery ct diameter, and round shape opacity had lower mortality. keywords: tomography scanners, x-ray computed; epidemiology; covid-19; severe acute respiratory syndrome coronavirus 2; mortality; prognosis; patient outcome assessment cite this article as: raoufi m, safavi naini s a a, azizan z, jafar zade f, shojaeian f, ghanbari boroujeni m, robatjazi f, haghighi m, arhami dolatabadi a, soleimantabar h, shoaee s, hatamabadi h. correlation between chest computed tomography scan findings and mortality of covid-19 cases; a cross sectional study. arch acad emerg med. 2020; 8(1): e57. ∗corresponding author: hamidreza hatamabadi; department of emergency medicine, imam hossein hospital, shahid madani avenue, imam hossein square, tehran 1617763141, iran. tel: +98 2173432380 fax: +98 2177557069, email: hhatamabadi@yahoo.com. 1. introduction corona virus disease 2019 (covid-19), was declared to be a global health emergency by the world health organization (who) on january 30th, 2020. it is necessary to recognize predictors of poor prognosis based on clinical manthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. raouf et al. 2 ifestations, laboratory tests, and radiologic patterns of lung involvement to properly deal with patients suspected to have covid-19 (1). analyses have introduced comorbidities such as chronic obstructive pulmonary disease (copd), diabetes, hypertension and malignancy, high sequential organ failure assessment (sofa) score, and higher levels of erythrocyte sedimentation rate (esr), d-dimer, albumin and il6 as poor prognostic factors, especially in older males (2-5). although rt-pcr has become a standard test for detecting patients, some studies have reported that clinical and radiological investigation could be used as an easier and more readily available way to detect patients, especially since it takes less time and has a lower cost compared to rt-pcr (69). with the passage of time from the onset of the symptoms, chest computed tomography (ct) scan findings become more frequent. the chest ct findings include consolidation, linear opacities, crazy-paving pattern, and the reverse halo with ground glass opacification being the predominant pattern (9-12). the chest ct scan severity score (ctss) was suggested as a quick means to evaluate the severity of pulmonary involvement with an optimal threshold of 19.5 out of 40 (13). ct scan features were indicated to be helpful in evaluation of the severity and extent of the disease (14) as well as monitoring the clinical course (15). consolidation, linear opacities, crazy-paving pattern, and bronchial wall thickening were reported to be significantly higher in severe/critical patients, who also had higher ct scores and more extra-pulmonary lesions (16). it is worth noting that many prediction models were presented in the academic literature and the most frequently reported predictors of prognosis included ct scan features (17). furthermore, pulmonary indication value was reported to be significantly correlated with the main clinical symptoms and laboratory results (18). based on the abovementioned facts, this study aimed to evaluate the correlation between chest ct scan findings and outcome of covid-19 cases. 2. methods 2.1. study design and setting this retrospective single-center cross sectional study was carried out on covid-19 patients diagnosed with clinical manifestations and chest ct scans based on iran’s national guidelines. these patients were admitted to the emergency department (ed) of imam hossein hospital, tehran, iran, from february 22th 2020, until march 22th 2020. the ethics committee of shahid beheshti university of medical science approved the study (ethics id: ir.sbmu.retech.rec.1399.003). informed consent was obtained from all those who were enrolled and confidentiality of patients’ data was maintained. figure 1: area under the receiver operating characteristic (roc) curve of chest computed tomography severity score in predicting covid-19 mortality. 2.2. participants cases with suspected covid-19 based on iran’s national guidelines for defining covid-19, whose chest ct scan findings were strongly in favor of covid-19, were enrolled in the study. based on this definition, patients with acute respiratory infection who do not positively respond to the usual pneumonia treatment or who have had recent travel history to china as well as patients having respiratory symptoms with any severity, who have had physical contact with an individual diagnosed with or suspected to have covid-19 were considered suspected cases for covid-19. definite diagnosis of the patients was based on chest ct scan and rt-pcr (for admitted cases). patients were excluded if they had a normal chest ct scan upon arrival to ed, two negative rt-pcrs, or declined to participate in the study. 2.3. data gathering using a predesigned checklist, demographic data (age, gender), underlying disease (diabetes mellitus, cardiovascular disease, smoking, kidney disease, asthma, respiratory diseases other than asthma, malignancy, hematologic disorders, rheumatologic disorders, neurologic disorders, use of steroids, hypertension), symptoms (fever, dyspnea, myalgia, headache, nausea, vomiting, chest pain, and etc.), vital signs, laboratory findings and outcome were collected for all cases. in addition, the chest ct scan findings, which were reported by an expert radiologist who was completely blind to clinical and laboratory findings, were recorded for all cases. low dose lung ct scans were performed for all patients using a 16 detector ct scanner (siemens; emotion; somatom) with patients in a supine position; other ct parameters were kvp: 100; mas: 50-100; pitch:1.5; thickness: 4mm. the winthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e57 dow was set as mediastinal (window level, 50 hu; window width, 400 hu) and lung (window level, -400 to 700 hu; window width, 1200±1500 hu). patients were instructed to hold their breath in order to minimize motion artifacts. an expert attending radiologist (with 10 years of experience), reviewed the chest ct scans of the patients for involvement and severity of each lobe, pattern of involvement (such as ground glass, consolidation, crazy paving and reverse halo), form of parenchymal involvement (such as round opacity, linear opacity and no specific form), distribution of lung abnormalities (peripheral, peribronchovascular and peri-hilar), associated findings (such as pleural effusion, pericardial effusion, mediastinal and hilar significant adenopathy and pulmonary solid nodules), severity of involvement (based on ctss), and pulmonary artery diameter (including main pulmonary trunk (mpa), right and left pulmonary arteries (rpa and lpa)). the widest short-axis diameter of the main, right and left pulmonary artery were measured on the transverse section at the level of bifurcation of pulmonary artery trunk. ctss, a semi-quantitative scoring, was used to estimate the severity of lung parenchymal involvement. each of the 5 lung lobes were visually scored from 0 to 5 as: 0) no involvement; 1) < 5% involvment, 2) 5-25% involvement, 3) 26-49% involvement 4) 50-75% involvement, and 5) >75% involvement. the total ctss was the sum of the individual lobar scores and ranged from 0 (no involvement) to 25 (maximum involvement). this scoring system was acquired from fenj pan and tianhe ye study (19). five medical students were responsible for data gathering under the direct supervision of an emergency medicine specialist. medical information of the patients was collected from their electronic hospital records. 2.4. statistical analysis analyses were performed using spss 21.0. the findings were presented as mean ± standard deviation or frequency (%). student t-test, chi-square, and fisher’s exact test were used for comparisons. significance level was considered as p <0.05. receiver operating characteristic (roc) curve was used for finding the best cut off point of total chest ctss in predicting the patients with higher risk of mortality. 3. results 3.1. baseline characteristics of studied cases three hundred eighty patients with the mean age of 53.62 ± 16.66 (18 âăş 97) years were evaluated (66.1% male). diabetes mellitus (22.81%), cardiovascular disease (13.2%), and hypertension (12.1%) were among the most frequent comorbidities among the patients. the most frequent presenting clinical symptoms were cough (60.3%), fever (55.8%), and dyspnea (48.2%), respectively. 154 (53.8%) cases were admitted to the hospital and 133 (46.2%) patients were discharged and managed at home. the total and in-hospital mortality rates during the 2-week follow up were 7.6% (29 from 380 cases) and 14.2% (22 from 154 cases) in this series, respectively. tables 1 and 2 compare the baseline characteristics and laboratory parameters between survived and nonsurvived cases. 3.2. chest ct scan findings the most frequent chest ct scan abnormalities were in peripheral (86.6%) and peribronchovascular interstitium (34.6%), with ground glass pattern (54.1%), and round (53.6%) or linear (46.7%) shape. the time between onset of initial symptoms and performing chest ct scan was less than 4 days in 30.8% (early stage), 4 6 days in 35.8% (intermediate stage), and more than 6 days in 33.3% (late stage) of patients. stage of disease had no correlation with pattern of chest ct scan involvement (p= 0.692). there was a significant correlation between stage of disease and ctss (p= 0.008). table 3 compares the chest ct scan characteristics of cases between survived and non-survived cases. there was a significant correlation between shape of abnormalities (p = 0.003), ctss (p <0.0001), and pulmonary artery ct diameter (p = 0. 01) with mortality. 3.3. correlation of ctss and mortality the mean ctss of non-survived cases was significantly higher (13.68 ± 4.59 versus 8.72 ± 4.42; <0.0001). the area under the roc curve of ctss in predicting the patients’ mortality was 0.800 (95% ci: 0.716-0.884; figure 1). the best cut off point of chest ctss in this regard was 12 with 75.82% (95% ci: 56.07%-88.98%) sensitivity and 75.78% (95% ci: 70.88%80.10%) specificity. 3.4. correlation of pulmonary artery diameter and ctss the mean main pulmonary artery diameter in patients with ctss ≥ 12 was higher than cases with ctss < 12 (27.89 ± 3.73 vs 26.24 ± 3.14 mm; p < 0.0001). the mean right pulmonary artery diameter was significantly higher in cases with higher ctss of right middle (p= 0.045) and right lower (p < 0.0001) lobes of the lung. in addition, the mean left pulmonary artery diameter was significantly higher in cases with higher ctss of left upper (p= 0.006) and left lower (p < 0.002) lobes of the lung. 4. discussion based on the results of the present study, it seems that there is a significant correlation between chest ct scan characteristics and mortality of covid-19 cases. patients with lower ctss, lower pulmonary artery ct diameter, and round shape opacity had lower mortality. ground glass opacity (ggo) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. raouf et al. 4 table 1: comparing the baseline characteristics of covid-19 patients between survived and non-survived cases variables total (n=380) survived (n=351) died (n=29) p value gender female 129 (66.1) 122 (94.6) 7 (5.4) 0.246 male 251 (33.9) 229 (91.2) 22 (8.8) age (year) mean ± sd 53.57 ± 16.66 52.85 ± 16.35 63.60 ± 17.68 0.002 comorbid disease yes 118 (40.8) 106 (89.8) 12 (10.2) 0.949 no 171 (59.2) 154 (90.1) 17 (9.9) presenting vital sign temperature (c) 37.34 ± 1.04 37.29 ± 1.00 37.94 ± 1.39 0.104 systolic bp (mmhg) 118.21 ± 11.61 118.40 ± 11.6 115.00 ± 12.90 0.572 respiratory rate (/min) 18.80 ± 4.32 18.36 ± 3.62 26.67 ± 8.62 0.001 heart rate (/min) 89.99 ± 14.50 88.92 ± 13.30 103 ± 22.81 0.016 saturation o2 (%) 93.43 ± 6.11 93.82 ± 5.88 87.13 ± 6.72 0.002 clinical manifestations fever 212 (55.8) 193 (72.0) 19 (65.5) 0.642 cough 229 (60.3) 209 (77.1) 20 (74.1) 0.720 dyspnea 183 (48.2) 163 (62.0) 20 (69.0) 0.460 myalgia 182 (47.9) 168 (63.2) 14 (51.9) 0.249 headache 128 (33.7) 121 (45.1) 7 (26.9) 0.074 chest pain 77 (20.3) 68 (26.1) 9 (34.6) 0.347 nausea or vomiting 98 (25.8) 88 (33.5) 10 (37.0) 0.708 disposition hospital admission 140 (48.6) 124 (47.0) 16 (66.7) icu admission 14 (5.2) 9 (3.4) 6 (25.0) < 0.001 home admission 133 (46.2) 131 (49.6) 2 (8.3) data are presented as mean ± standard deviation (sd) or frequency (%). bp: blood pressure; icu: intensive care unit. and consolidation were the most frequent chest ct scan findings, which was consistent with other studies (20, 21). the most common location of abnormalities was peripheral, followed by peribronchovascular interstitium. lower zone involvement was observed more than upper zone, which was consistent with findings of other studies (2, 22). in order to evaluate the severity of lung involvement via ct, we used lobar severity score, which was significantly higher in deceased patients, in comparison with survived group, like chen et al. and yuan et al. studies (2, 21). an investigation on 121 patients carried out by bernheim et al. revealed that the longer since the onset of symptoms, ct findings became more prominent (9). similar to this study, our assessment has demonstrated that patients that presented at earlier stages had lower ctss. radiological patterns did not correlate with stage of the disease, which was in contrast to other studies (9, 19). the best cut off of chest ct score in predicting mortality in the present study was 12 out of 25, with acceptable sensitivity and specificity of 75.82% and 75.78%, respectively. however, yang et al. used a different system, scoring 20 pulmonary regions in range of 0-2 with the best cut off point of 19 out of 40 with 94% specificity and 83% sensitivity (2). considering shapes of ct scan abnormalities, round opacities correlated with better prognosis. to explain better prognosis of round opacities, more investigation is needed to understand whether this is due to early medical treatment or possible low viral load of the patients as discussed by jsm peiris et al. for sars (19, 23). hani et al. demonstrated that ct scan patterns of covid-19 patients could transform to organizing pneumonia and lung fibrosis as a sequela in advanced phases, which has also been concluded in other studies (24, 25). therefore, for future follow up of pulmonary artery hypertension secondary to lung injury, we measured mpa, rpa, and lpa diameters as a baseline. although mean pulmonary artery diameters (pad) in survived and non-survived group was not beyond the normal range, the differences between them were statically significant. therefore, it could be used to predict patient prognosis. it is worth noting that the small differences between mean pad of groups (about 2 millimeters), could raise concerns for operator dependent errors. although pad increase, an indicator of pulmonary hypertension secondary to lung fibrosis, is expected in long term, acute rise of pad could occur due to lung injury. as mentioned before, patients whose diseases progressed to acute respiratory distress syndrome, showed dilation of pulmonary arteries in days (26). this research was carried out to explore chest ct scan prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e57 table 2: comparing the laboratory findings of covid-19 patients between survived and non-survived cases characteristics survived (n=351) died (n=29) p value complete blood count wbc (109 /l) 6.90 ± 3.96 11.46 ± 7.96 < 0.0001 hemoglobin (g/dl) 13.14± 1.91 12.85 ± 2.09 0.285 hematocrit (%) 39.03 ± 5.13 38.21 ± 5.49 0.401 platelet (109 /l) 195.15 ± 83.13 183.50 ± 62.60 0.487 lymphocyte (%) 22.66 ± 11.37 11.42 ± 5.59 < 0.0001 neutrophil (%) 69.81 ± 12.76 82.58 ± 6.55 < 0.0001 blood gas analysis ph 7.43 ± 0.09 7.38 ± 0.17 0.038 po2 (mm hg) 34.50 ± 18.57 36.33 ± 24.96 0.654 pco2 (mm hg) 41.99 ± 10.76 37.32. ± 11.75 0.053 hco3 (meq/l) 27.01. ± 7.10 23.38 ± 7.01 0.016 coagulation profile pt (s) 12.73 ± 3.17 15.07 ± 3.82 0.010 ptt (s) 28.27 ± 9.91 29.82 ± 5.32 0.526 inr (iu) 2.33 ± 10.57 1.35 ± 0.38 0.696 liver enzymes ast (u/l) 64.38 ± 234.43 104.56 ± 117.76 0.533 alt (u/l) 58.09 ± 208.98 63.78 ± 47.53 0.926 kidney enzyme urea ( mg/dl) 42.78 ± 33.42 66.81 ± 53.83 0.001 creatinine (mg/dl) 1.97 ± 9.32 1.69 ± 0.95 0.877 others sodium (meq/l) 137.43 ± 4.00 136.26 ± 7.13 0.187 potassium (meq/l) 3.97 ± 0.61 4.09 ± 0.79 0.325 calcium (mg/dl) 8.23 ± 1.20 7.90 ± 0.82 0.314 magnesium (mg/dl) 2.20 ± 1.50 2.09 ± 0.42 0.774 esr (mm/hr) 49.56 ± 26.30 54.21 ± 31.03 0.486 crp (mg/l) 46.47 ± 42.77 89.89 ± 68.71 < 0.0001 cpk (u/l) 216.38 ± 474.51 1033.45 ± 1754.19 < 0.0001 blood sugar(mg/dl) 154.48 ± 71.49 159.54 ± 85.21 0.816 data are presented as mean ± standard deviation. wbc: white blood cell; pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio; ast: aspartate aminotransferase; alt: alanine aminotransferase; esr: erythrocyte sedimentation rate; crp: c-reactive protein; cpk: creatinine phosphokinase. dictors of prognosis in covid-19 patients. we found out that radiologic features, especially ct scan severity score, can be helpful in management of patients, along with clinical manifestations. moreover, we found that pulmonary artery diameter correlated with ct scan severity score and prognosis, although more investigations are needed. 5. limitation lack of rt-pcr in patients managed in an out-of-hospital setting, recall bias of patients during phone interviews, interpretation of ct scan images by only one person, differences between iran’s national guideline for covid-19 and guidelines of other countries, in addition to usual limitations of cross sectional studies, were among the most important limitations of this study. 6. conclusion based on the results of the present study it seems that there is a significant correlation between chest ct scan characteristics and mortality of covid-19 cases. patients with lower ctss, lower pulmonary artery ct diameter, and round shape opacity had lower mortality. 7. declarations 7.1. acknowledgements the authors would like to acknowledge all the self-giving healthcare workers and appreciate the serenity of people. the assistance provided by iman nilforushan and hosseinali safavi-naeini for english editing is much appreciated. 7.2. author contribution all authors met the criteria for authorship contribution based on recommendations of international committee of medithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. raouf et al. 6 table 3: comparing the chest computed tomography (ct) scan findings of covid-19 patients between survived and non-survived cases characteristics survived (n=351) died (n=29) p value location peripheral 304 (86.6) 25 (88.2) 1.000 peribronchovascular 122 (34.8) 10 (34.5) 0.976 perihilar 1 (0.3) 0 (0.0) 1.000 upper zone 23 (6.6) 0 (0.0) 0.240 lower zone 60 (17.1) 5 (17.2) 0.984 upper and lower zone 87 (24.8) 8 (27.6) 0.738 presentation ground glass 190 (54.1) 15 (51.4) 0.996 consolidation 104 (29.6) 9 (31.0) shape round opacity 188 (53.6) 6 (20.7) 0.003 linear opacity 150 (42.7) 15 (51.7) 0.348 non specified 20 (5.7) 5 (17.2) 0.016 crazy paving 11 (3.1) 3 (10.3) 0.082 lobar ctss right upper lobe 1.71 ± 0.78 2.25 ± 0.96 0.001 right middle lobe 2.02 ± 0.82 2.71 ± 0.93 < 0.0001 right lower lobe 2.45 ± 0.86 3.25 ± 0.79 < 0.0001 left upper lobe 2.15 ± 0.86 3.76 ± 1.14 0.001 left lower lobe 2.31 ± 0.89 3.21 1.13 < 0.0001 total ctss mean ± sd 8.72 ± 4.42 13.68 ± 4.59 <0.0001 pa diameter (mm) main 26.54 ± 3.29 28.93 ± 3.99 <0.0001 right 17.84 ± 3.23 19.61 ± 4.11 0.007 left 17.61 ± 2.86 19.61 ± 2.58 <0.0001 data are presented as mean ± standard deviation (sd) or frequency (%). ctss: computed tomography severity score. pa: pulmonary artery. cal journal editors. m.r and h.h conceived the presented idea. h.h. and m.r. and s.a.s. and f.sh and m.g. wrote the manuscript. h.h and m.r. and e.f. conceived the study and were in charge of overall direction and planning with the help of s.a.s. z.a. and f.j. and s.a.s and f.sh and m.g collected the data through hospital information system and calling the patients. m.r. and f.r examined radiology. z.a. and f.j. filled out the radiologic forms. all authors discussed the results and commented on the manuscript. authors orcids masoomeh raoufi: 0000-0001-7269-1822 seyed amir ahmad safavi naini: 0000-0001-9295-9283 zahra azizan: 0000-0002-2872-3599 fatemeh jafar zade: 0000-0001-5367-4859 fatemeh shojaeian: 0000-0001-5972-9953 masoud ghanbari boroujeni: 0000-0002-6220-2797 farzaneh robatjazi: 0000-0003-0651-0397 mehrdad haghighi: 0000-0003-3139-3225 ali arhami dolatabadi: 0000-0001-9492-9520 hossein soleimantabar: 0000-0003-3329-0406 simindokht shoaee: 0000-0003-3127-4875 7.3. funding/support this research was supported by grants from vice chancellor of research and technology of shahid beheshti university of medical science (grant number: 22973). 7.4. conflict of interest the authors disclose that they have no competing interests. references 1. huang h, cai s, li y, li y, fan y, li l, et al. prognostic factors for covid-19 pneumonia progression to 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prognostic factors based on 4-week follow-up. journal of infection. 2020. 26. price lc, mcauley df, marino ps, finney sj, griffiths mj, wort sj. pathophysiology of pulmonary hypertension in acute lung injury. american journal of physiology-lung cellular and molecular physiology. 2012;302(9):l803l15. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e86 or i g i n a l re s e a rc h acep’s recommendations for brain computed tomography scan in adult minor head trauma patients; a diagnostic accuracy study mohammad mohammaddoust1, niaz-mohammad jafari chokan2, seyedeh maryam moshirian farahi3, ayoub tavakolian4, mahdi foroughian2∗ 1. department of emergency medicine, mashhad university of medical sciences, mashhad, iran. 2. department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. department of psychology, salman institute of higher education, mashhad, iran. 4. department of emergency medicine, faculty of medicine, sabzevar university of medical sciences, sabzevar, iran. received: august 2020; accepted: september 2020; published online: 29 october 2020 abstract: introduction: some clinical decision rules have been developed to identify minor head trauma (mht) patients in need of brain computed tomography (ct) scan for detection of possible traumatic brain injuries (tbis). this study aimed to evaluate the performance of american college of emergency physicians (acep) recommendations in this regard. methods: this study is a cross-sectional study of mht (gcs: 13-15) cases who referred to emergency department of a level one trauma center, mashhad, iran, from october 2017 to march 2018. the screening performance characteristics of acep recommendations for performing brain ct scan in these patients were calculated. results: 500 patients with a mean age of 37.97 ± 15.96 years were evaluated. based on level one recommendations, 73 (14.6 %) patients had to be assessed by brain ct scan. 67 (91.8%) were assessed and 6 (8.2%) were not assessed based on decision of their in-charge physician. according to level two recommendations, 125 (25.0%) patients did not need brain ct scan, 85 (68%) of whom had been assessed (all normal). performing brain ct scan according to the level one recommendation of acep’s clinical policy showed 29.6% sensitivity (95% ci: 13.75 to 50.18) and 86.3% specificity (95% ci: 82.68 to 89.14). the overall acep’s clinical policy for neuroimaging of adults with mtbi showed sensitivity and specificity of 92.59% (95% ci: 75.71 to 99.09) and 26.4% (95% ci: 22.51 to 30.65), respectively. conclusion: acep’s clinical policy has a high-level sensitivity for using brain ct scan in detection of probable tbi in patients with mht. keywords: craniocerebral trauma; brain; tomography, x-ray computed; health planning guidelines cite this article as: mohammaddoust m, jafari chokan n m, moshirian farahi s m, tavakolian a, foroughian m. acep’s recommendations for brain computed tomography scan in adult minor head trauma patients; a diagnostic accuracy study. arch acad emerg med. 2020; 8(1): e86. 1. introduction minor head trauma (mht) is blunt trauma to the head in patients with gcs scores between 13 to 15 secondary to the trauma (1). traumatic brain injury (tbi) indicates an injury to the brain itself and more than 75% of treated tbi cases are mild (2). mild tbi is a common neurological disorder and only 0.4% to 1% of these injuries require neurosurgical inter∗corresponding author: mahdi foroughian; department of emergency medicine, faculty of medicine, mashhad university of medical sciences, mashhad, iran. tel: 05138525312; email: foroughianmh@mums.ac.ir vention (3). the most important issue in patients with minor head trauma is to identify patients with probable intracranial injuries who require hospitalization and proper management. brain ct scan is the standard imaging modality for detecting intracranial injury of trauma patients in emergency department (ed). most of these patients (80-90%) do not need to be admitted, and almost all of them are discharged with appropriate instructions. the common use of brain ct scans is associated with exposure to ionizing radiation and high healthcare costs, considering the large number of people affected (4). therefore, some clinical decisionmaking rules have been developed to find mht patients who are susceptible to intracranial lesions on ct scans in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammaddoust et al. 2 ed. some of the important clinical decision rules are the canadian ct head rule (cchr), the new orleans criteria (noc), the national emergency x-radiography utilization study ii (nexus ii) criteria, and american college of emergency physicians (acep) clinical policy (5, 6). in many studies, the efficacy of these guidelines, such as cchr, noc, and nexus ii, has been evaluated (7-9). however, the best guideline to be used in routine practice may be highly dependent on the ed’s policies and situation and level of infrastructures availability (7-12). according to one study, which was done in taiwan, the sensitivity and specificity of acep guideline were 75.97% and 34.68%, respectively. the study concluded that, although acep guideline reduced unnecessary brain ct scans, it wasn’t an appropriate guideline for use in taiwan (13). based on the above-mentioned points, this study aimed to evaluate the accuracy of acep’s recommendation in identifying mht patients in need of brain ct scan and ruling out of susceptible intracranial injuries. 2. methods 2.1. study design and setting this prospective cross-sectional study was conducted on adult mht patients (gcs score of 13 to 15 one day after trauma) who referred to the ed of a hospital affiliated to mashhad university of medical sciences (level one trauma center), mashhad, iran, from 2017 to march 2018. the screening performance characteristics of acep recommendations for performing brain ct scan in these patients were calculated. this study has been approved by the ethics committee of mashhad university of medical sciences under the ethics code of ir.mums.fm.rec.1396.70. 2.2. participants this study has evaluated patients with minor head trauma (gcs≥13), 18 years old or older who referred to the trauma center. patients aged less than 18 years and those with an obvious penetrating skull injury, unstable vital signs associated with major trauma, and pregnancy were excluded. 2.3. study protocol the acep recommendations were taught to emergency residents responsible for data gathering. brain ct scans were performed based on the opinion of emergency physicians. patients who were discharged without a brain ct scan were followed in 2 weeks and were asked to come back to the ed immediately if they encountered any unusual symptoms (as previously announced). therefore, patients who were asymptomatic after 2 weeks were considered as brain damage-free cases. table 1: baseline characteristics of study population characteristics number (%) gender male 335 (67.0) female 165 (33.0) age (year) ≤ 60 449 (89.8) > 60 51 (10.2) trauma mechanism falling down 30 (6.0) motor vehicle collision 174 (34.8) passenger-related accident 60 (12.0) hitting injury (assault) 172 (34.4) other 64 (12.8) signs and symptoms post-traumatic amnesia 54 (10.8) vomiting 37 (7.4) short memory loss 22 (4.4) coagulopathy 3 (0.6) decreased level of consciousness 31 (6.2) moderate headache 88 (17.6) severe headache 123 (24.6) intoxication 16 (3.2) trauma above the clavicle 115 (23.0) 2.4. data gathering after history taking and performing physical examination, demographic characteristics and clinical symptoms and signs of the patients were recorded on a checklist that had been designed based on acep recommendations (1). 2.5. statistical analysis the data were entered into spss 22 (spss inc., chicago, illinois, usa). to assess the accuracy of acep recommendations, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios as well as area under the receiver operating characteristic (roc) curve were calculated and reported with 95% confidence interval (ci). the findings were presented as mean ± standard deviation or frequency (%). 3. results 3.1. baseline characteristics of studied cases 500 patients with a mean age of 37.97 ± 15.96 (18 – 90) years were evaluated (67% male). table 1 shows the baseline characteristics of studied case. the most frequent trauma mechanisms were motor vehicle collision (34.8%) and direct hitting on the head (34.4%), respectively. brain ct scan was done for 404 (80.0%) cases based on the in-charge physicians’ decision. the frequency of acep-recommended variables for doing brain ct scan have been shown in table 2. the most frequent symptoms that indicated performance of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e86 table 2: frequency of level one and two acep-recommended variables in the study population variables number (%) level one post-traumatic amnesia 54 (10.8) vomiting 37 (7.4) short memory loss 22 (4.4) coagulopathy 3 (0.6) headache 211 (42.2) age> 60 year 51 (10.2) intoxication 16 (3.2) trauma above the clavicle 115 (23.0) post-traumatic seizure 0 (0.0) focal neurological deficit 0 (0.0) level two focal neurological deficit 0 (0.0) vomiting 37 (7.4) severe headache 123 (24.6) age ≥ 65 year 40 (0.8) basilar skull fracture 0 (0.0) gcs < 15 31 (6.2) coagulopathy 3 (0.6) dangerous mechanism of injury 195 (39.0) brain ct scan based on level one and two recommendations, were headache (42.2%) and dangerous mechanism of trauma (39%), respectively. 3.2. brain ct scan; indications and findings level one recommendation based on level one recommendations, 427 (85.4%) patients did not need brain ct scan, 337 (78.9%) of which were assessed by ct scan, based on the decision of their in-charge physician (318 (94.4%) normal, 2 (0.59%) intracranial hemorrhage, 1 (0.29%) epidural hematoma, 4 (1.18%) subarachnoid hemorrhage, and 12 (3.56%) skull fracture). based on this level of recommendation, 73 (14.6 %) patients should have been assessed by brain ct scan [6 (8.2%) were not assessed based on decision of their in-charge physician (1(1.5%) intracranial hemorrhage, 1 (1.5%) epidural hematoma, 1(1.5%) subarachnoid hemorrhage, 1 (1.5%), intra-ventricular hemorrhage and 2 (6%) skull fracture]. level two recommendation based on level two recommendations, 125 (25.0%) patients did not need brain ct scan, 85 (68%) of which had been assessed (all normal). also based on this level of recommendations, 375 (75.0%) patients should have been assessed by ct scan, 319 (85%) of which had been assessed (292 (91.5%) normal, 3(0.94%) intracranial hemorrhage, 2 (0.65%) epidural hematoma, 5 (1.6%) subarachnoid hemorrhage, 1 (0.31%) intra-ventricular hemorrhage, and 16 (5%) skull fracture). screening performance characteristics of acep recommendations doing brain ct scan according to level one recommendations of acep’s clinical policy showed 29.6% sensitivity (95% ci: 13.75 to 50.18) and 86.3% specificity (95% ci: 82.68 to 89.14). overall, acep’s clinical policy for neuroimaging of adults with mtbi showed sensitivity and specificity of 92.6% (95% ci: 75.71 to 99.09) and 26.4% (95% ci: 22.51 to 30.65), respectively (table 3). 4. discussion this study, found that the acep criteria for conducting brain ct scan in traumatic brain injury is highly sensitive (92.59%) for finding pathologies in patients with minor head trauma. the acep criteria identify patients who need to undergo a brain ct scan in two levels (14). based on the criteria, patients who have symptoms or signs according to the first level of recommendation should be assessed via ct scan (14). this study shows that conducting a brain ct scan only based on the first level of recommendation has low sensitivity (29.6%) but relatively high specificity (86.3%). the high specificity of the first level of this criteria shows that the recommendation of acep criteria for conducting brain ct scan for all patients corresponding to the first level of acep criteria is completely reasonable (14), while low sensitivity of the first level of recommendation shows that conducting brain ct scan only based on the first level of recommendation leads to missing many patients with tbi (15). the second level of acep criteria states that ct scan should be performed only for some of the patients corresponding to this level (16). the results of our study confirm the recommendation of the acep criteria. when patients corresponding to the second level of recommendations underwent a ct, the sensitivity of this study extremely increased, while it’s specificity extremely decreased, which means that the number of patients undergoing ct scan with no indication and normal ct results increased. therefore, based on these criteria it’s better to observe patients corresponding to the second level of acep criteria and not conduct a brain ct scan once they arrived at the emergency department. this observation will indicate which patients need to undergo brain ct scan (17). the sensitivity of our study was higher than the study performed in taiwan, while the specificity of our study was lower (13). the review of literature shows that similar studies, which investigate the effectiveness of the acep criteria, are rare. while several studies have investigated other guidelines such as cchr, noc, and nexus ii. in these studies, the sensitivities of cchr and noc were (100, and 95 %) and (10099%), respectively; also, the specificities of cchr and noc were (47-70%) and (3-31%), respectively (1, 7, 13, 18-20). another study, which has been done on the nexus ii criteria, has reported the sensitivity and specificity of this guideline as (100%) and (33%), respectively (21). ro and et al. compared this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. mohammaddoust et al. 4 table 3: screening performance characteristics of acep-recommended criteria (level one, two, and overall) for performing brain computed tomography scan in patients with minor head trauma characters level one level two one + two (0verall) value 95% ci value 95% ci value 95% ci sensitivity 29.61 13.75 50.18 89.49 66.86 -98.70 92.59 75.7199.09 specificity 86.28 82.6889.14 26.33 21.9531.95 26.41 22.5130.65 ppv 11.00 6.76 20.24 6.80 5.817.94 7.80 7.06 8.80 npv 94.00 92.88 95.55 97.70 91.8899.38 97.00 91.70 99.39 plr 2.12 1.15 3.99 1.22 1.03 -1.44 1.30 1.12 1.42 nlr 0.81 0.64 1.05 0.39 0.10 1.48 0.32 0.07 1.07 accuracy 80.59 76.50 84.43 30.21 25.4135.48 27.21 22.94 31.85 ci: confidence interval; ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio. the predictive performance of cchr, noc, and nexus ii, for detecting clinically important tbi. the mentioned study showed that their sensitivity and specificity for clinically important brain injury were as follows: cchr, (79.2%, 95%) and (41.3%, 95%); noc, (91.9%, 95%) and (22.4%, 95%); and nexus-ii, (88.7%, 95%) and (46.5%, 95%), respectively (12). in the present study, the sensitivity found for acep was similar to those found for other guidelines in previous studies, and it was shown that it can detect almost all pathological cases of mild tbi; whereas the specificity of acep is lower than cchr and nexus ii and higher than noc. as a result, compared to other guidelines, cchr could best decrease excessive use of ct. though acep guidelines increased using ct scan, if physicians pay further attention to choose patients in the second level of the recommendation of acep to do a ct scan it will be a useful guideline. 5. limitation this study only assessed the acep guideline and did not assess other guidelines to compare them. the study was done in a single trauma center. some patients cooperated poorly and were, therefore, excluded from this study. 6. conclusion the findings revealed that acep’s recommendation for performing brain ct scan in mht patients has 92% sensitivity and 26% specificity. it could be a useful guideline to decrease the number of unnecessary ct scans, reduce radiation, and avoid extra costs for the patient and the healthcare system. 7. declarations 7.1. acknowledgements we would like to thank the clinical 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bahattinisik comparison of the canadian ct head rule and the new orleans criteria in patients with minor head injury world journal of emergency surgery 2014 9:31, doi: 10.1186/1749-7922-9-31. 19. linda p, ian gs, catherine mc, artur p, andrew w, sameer d, et al. performance of the canadian ct head rule and the new orleans criteria for predicting any traumatic intracranial injury on computed tomography in a united states level i trauma center. academic emergency medicine 2012; 19:2–10. 20. schachar jl, zampolin rl, miller ts, farinhas jm, freeman k, taragin bh. external validation of the new orleans criteria (noc), the canadian ct head rule (cchr) and the national emergency x-radiography utilization study ii (nexus ii) for ct scanning in pediatric patients with minor head injury in a non-trauma center. pediatric radiology. 2011 aug 1;41(8):971. 21. mower wr, gupta m, rodriguez r, hendey gw. validation of the nexus ii pediatric head computed tomography decision instrument. the journal of emergency medicine. 2017 sep 30;53(3):441. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e19 le t t e r to ed i to r information typology in coronavirus (covid-19) crisis; a commentary hasan ashrafi-rizi1∗, zahra kazempour2 1. medical library and information science department, health information technology research center, isfahan university of medical sciences, isfahan, iran. 2. library and information science department, faculty of media, payame noor university, tehran, iran. received: march 2020; accepted: march 2020; published online: 12 march 2020 cite this article as: ashrafi-rizi h, kazempour z. information typology in coronavirus (covid-19) crisis; a commentary. arch acad emerg med. 2020; 8(1): e19. 1. introduction in late 2019 and early 2020, many people in different countries around the world became infected by the new coronavirus. this created challenges for these countries in many aspects including economic, political, social, health and so on. some of these challenges are directly or indirectly related to information discussion, because providing the right information, at the right time and to the right audience, can solve or reduce some of the challenges. however, there were problems in this process during this crisis, as various individuals and organizations began to produce and disseminate information that, given the special circumstances of this crisis (that most countries have rarely experienced), produced types of information that are worth consideration. 2. methods in a commentary, the author(s) seek to present new views to researchers on a particular topic. a commentary may also draw attention to current advances and speculate on future directions of a certain topic (1). accordingly, the authors of this commentary began to review scientific texts and messages published in the mass and social media on the coronavirus. also, authors used previous knowledge and experience, particularly in the areas of health information behavior, health information literacy, and media literacy. the messages were analyzed and categorized by the authors, and the information typology was selected based on the categories of the messages and their context. in addition, the views of two ∗corresponding author: hasan ashrafi-rizi; medical library and information science department, health information technology research center, isfahan university of medical sciences, isfahan, iran. email: hassanashrafi@mng.mui.ac.ir, tel: +989132365178 other researchers on content and terms were also obtained. in this commentary, the authors attempted to take into account any information produced and published during the coronavirus crisis. 3. types of information 3.1. valid information these are information that is based on the latest scientific evidence and is citable and applicable to others. for example, hand washing with a certain protocol can lead to elimination of the coronavirus. 3.2. comforting information these are information whose production and dissemination makes people happy and relaxed during the crisis. in the current coronavirus crisis, jokes, animations, poem manipulation, mass media entertainment and other content that decreased an individual’s fears and anxieties about the coronavirus for moments, were instances of comforting information that act like a safety valve. 3.3. perplexing information the kind of scientific information that has been produced in order to increase the knowledge of others, but is sent to an unrelated audience, is called perplexing information. for example, some high-level scientific information about coronavirus is sent to the general public or adolescents, who do not have enough knowledge and cannot understand it, which can in turn exacerbate their concerns. on the other hand, sometimes some simple content is sent to health professionals, for whom the content is elementary, and this can lead to wasting their time. most of this content is shared on online social networks. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem h. ashrafi-rizi & z. kazempour 2 3.4. misinformation this type of information is inaccurate and unreliable but the distributer of that information disseminates it inadvertently and pays little attention to the effects of this information on the society (2). in the coronavirus crisis, bad news that was spread through online social networks such as whatsapp, telegram, etc. regarding the number of infected and dead people increased the fear and anxiety among people. however, if this kind of news is produced and distributed on purpose, it is no longer called misinformation; it is named disinformation because the producer(s) pursued inhumane purposes. 3.5. disinformation this is the type of inaccurate information whose producers and distributors pursue political, economic, cultural, or other purposes and intentionally produce and disseminate it. this type of information is intentional, forging, and manipulative and distorts reality (2). this kind of information is usually produced and disseminated by rancorous people. for example, a message on the social media stated that a bahraini officer said that the iranian president and all his cabinet members were suffering from coronavirus disease. 3.6. shocking information reading or hearing this type of information makes the recipient consternated, shocked and anxious. for example, in the early days of the coronavirus crisis, information that illustrated the dangerous nature and behavior of the virus, like its contagiousness, was sent to the world from china. this information was unbelievable and terrifying to the general public. 3.7. contradictory information this type of information is produced and disseminated due to a difference of opinion between experts on a topic. in the current coronavirus crisis, some experts initially declared that using a mask in the public was necessary, but some disagreed. some even stated that the world health organization has behaved differently in this case. 3.8. doubtful (untrusted) information this type of information cannot be validated or discredited due to insufficient scientific evidence. for example, in case of the new coronavirus, some have claimed that peganum smoke and consumption of garlic or other foods are helpful in disease prevention, and some have dismissed their effectiveness. the accuracy of these claims should be scientifically evaluated by health researchers. 3.9. progressive information this type of information fosters or leads to innovation, creativity, and production of new content in the future. for example, information obtained by health researchers about the nature and function of the virus during the coronavirus crisis will be the basis for future studies. this is the reason that it has been stated that the choice of research topics should be based on need. in fact, it is an example of research based on society’s needs. 3.10. postponed information this information is presented to others with delay. if information is temporarily withheld, it will result in a consequence like distrust in society. for example, some countries initially did not disclose the number of cases infected with coronavirus, but with the increasing number of patients, they were forced to provide information. 3.11. confidential information this type of information is never revealed for various reasons and there is deliberation and expedience in hiding them. it is clear that many countries will not disclose the exact number of infected and death cases, because a greater number indicates the weakness of the governments and their health structure. 4. conclusion this will not be the first and last pandemic crisis in the world. it is important for a community to know how to manage and steer through that crisis and experts should develop appropriate behavioral patterns for both people and professional as well as government officials by gaining experience from this crisis and similar ones over the time. the proper behavioral pattern helps the community to get through the crisis with minimum cost (material and spiritual). in this behavioral pattern, attention must be paid to producers and disseminators of information, including the media, government officials, professionals in various fields (physician, nurses, psychologists, etc.) and even the public. media professionals and medical librarians, can play an important role in finding the best behavioral model for dealing with crises due to having the necessary knowledge and awareness about information production and dissemination infrastructure and familiarity with the typology of information. in the field of prevention, teaching information literacy and health literacy, and explaining appropriate behavior in times of crisis are other actions that media professionals and medical librarians should consider. finally, educating people on differentiating credible information from unreliable information will be the most important action taken by librarians and informants in the face of crises. it is hoped that this crisis expethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e19 rience will encourage medical librarians to become more active and have a more effective presence in future disasters. in conclusion, it should be mentioned that some of these types are based on the authors’ understanding and inference, so everyone is welcome to help the authors improve these concepts. at the same time, lack of relevant information resources and categorization of these contents are some of the limitations of this study. therefore, generalization of findings should be made more carefully. 5. declarations 5.1. acknowledgment authors wish to thank the staff members of school of management and medical information sciences, isfahan university of medical sciences, isfahan, iran. 5.2. author’s contribution h. a. conceived the original idea, designed the scenarios and collected the data. h. a. and z. k: carried out the analysis of data, drafted the manuscript approved the final version that was submitted, and revised it. all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids hasan ashrafi-rizi: 0000-0001-6052-2087 zahra kazempour: 0000-0001-6834-2814 5.3. conflict of interest the authors have declared that no competing interest exists. 5.4. funding and support this article resulted from an independent research without financial support. references 1. bertero c. guidelines for writing a commentary. international journal of qualitative studies on health and wellbeing. 2016;11:31390. 2. hamid k. information seeking: from information needs to information credibility. tehran: ketabdar publishing; 2015. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods types of information conclusion declarations references march 25, 2020 no. 11 total lab-confirmed cases: 27,017 total associated deaths: 2,077 total recovered cases: 9,625 new cases: 2,206 indicators of screened, infected and death cases screening (since march 4 till march 25, 2020; 5:30 pm gmt) value number of services delivered for covid-19 49,188,450 proportion of the target population required follow-up (%) 3.7 proportion of eligible cases that are followed-up by hws (%) 54 proportion of the target population with symptoms (%) 1.5 proportion of screened symptomatic cases referred to clinic (%) 0.2 proportion of referred cases that are visited by the physician (%) 0.8 proportion of visited cases that required homecare (%) 25.7 proportion of visited cases that received dual-medication (%) 0.6 proportion of visited cases that referred to the hospital (%) 4.5 proportion of hospital referrals that are admitted in the hospital (%) 32.9 clients’ satisfaction of the received services (%) 97.3 new lab-confirmed cases (in last 72 h) age mean (standard deviation) 56.5 (18) age median (inter-quartile range) 57 (42-71) sex distribution (%) male 53.5 female 46.5 cases with at least one co-morbidity (%) 30 cases admitted in icu* (%) 11.1 cases with more severe forms of the disease ** 15 covid-19 deaths (in last week)§ age mean (standard deviation) 69.5 (15.6) age median (inter-quartile range) 72 (62-81) cases over 60 years (%) 78.3 sex distribution (%) male 55.8 female 44.2 cases with at least one co-morbidity (%) 37.7 cases over 60 years or with at least one co-morbidity (%) 88.4 * to the total number of hospitalized covid-19 patients. ** based on available data, we considered patients with death outcome, as well as those admitted to icu or under mechanical ventilation as more severe cases. the information in this chart is based on hospitalized cases, and outpatients are not included in this calculation. inclusion of outpatients and asymptomatic cases would decrease the proportion of severe cases. § to increase the sample size, analysis of death cases is done on the data in the last week. lab-confirmed & discharged cases proportion of the target population screened for covid-19 by province next report will be released on march 28, 2020 source: national committee on covid-19 epidemiology, ministry of health and medical education, ir iran 0 500 1000 1500 2000 2500 n um be r lab-confirmed and cured cases confirmed cases cured cases 0 50 100 150 200 19 -f eb 21 -f eb 23 -f eb 25 -f eb 27 -f eb 29 -f eb 2m ar 4m ar 6m ar 8m ar 10 -m ar 12 -m ar 14 -m ar 16 -m ar 18 -m ar 20 -m ar 22 -m ar 24 -m ar lab-confirmed deaths mild 90% severe 10% 0 5 10 15 20 25 age distribution of lab-confirmed deaths 0 5 10 15 20 25 pe rc en t age distribution of lab-confirmed hospital dischared cases percent archives of academic emergency medicine. 2020; 8(1): e20 or i g i n a l re s e a rc h accuracy of alvarado, eskelinen, ohmann, ripasa and tzanakis scores in diagnosis of acute appendicitis; a cross-sectional study mustafa korkut1, cihan bedel1∗, yusuf karancı1, ali avcı2, murat duyan1 1. department of emergency medicine, health science university antalya training and research hospital, antalya, turkey. 2. department of emergency medicine, karaman state hospital, karaman, turkey. received: january 2020; accepted: february 2020; published online: 13 march 2020 abstract: introduction: many scoring systems have been developed to assist in diagnosis of acute appendicitis (aa). this study aimed to compare the screening performance characteristics of alvarado, eskelinen, ohmann, raja isteri pengiran anak saleha (ripasa), and tzanakis scores in predicting the need for appendectomy in aa patients. methods: our study prospectively evaluated aa patients that were treated in a tertiary hospital’s emergency department. the obtained data were used to calculate alvarado, tzanakis, ripasa, eskelinen and ohmann scores. patients were categorized into two groups according to their histopathological results: positive (pa) and negative appendectomy (na). the accuracy of different scoring systems in diagnosing aa was investigated. results: 74 patients suspected to aa with the mean age of 36.68 ± 11.97 years were studied (56.8% male). the diagnosis was histopathologically confirmed in 65 cases (87.8%). median alvarado, tzanakis, ripasa, eskelinen and ohmann scores were significantly higher in patients with positive appendectomy. the area under the curve (auc), sensitivity, and specificity of tzanakis score in the cut-off value of 8 were 0.965, 84.4%, and 100%, respectively. for ohmann and alvarado scores, these measures were 0.941; 71.9%, 89.9% and 0.938, 60.9%, 89.9%, respectively. tzanakis scoring system had the best screening performance in detection of cases with aa. conclusion: tzanakis score is more sensitive and specific than alvarado, ripasa, eskelinen and ohmann scores in identifying aa patients needing appendectomy. keywords: appendicitis; emergency medicine; diagnosis; sensitivity and specificity; alvarado, eskelinen, ohmann, raja isteri pengiran anak saleha appendicitis, tzanakis cite this article as: korkut m, bedel c, karancıy, avcıa, duyan m. accuracy of alvarado, eskelinen, ohmann, ripasa and tzanakis scores in diagnosis of acute appendicitis; a cross-sectional study. arch acad emerg med. 2020; 8(1): e20. 1. introduction acute appendicitis (aa) is the most common reason for surgical intervention among patients admitted to the emergency department (ed) with abdominal pain (1). approximately one-third of aa cases present with atypical clinical symptoms (2). perforation and negative appendectomy (na) rates were as high as 12-21% and 13-36%, respectively, for patients that were diagnosed solely through physical examinations (3, 4). in recent years, many scoring systems have been developed based on anamnesis scores, clinical symptoms and findings, ∗corresponding author: cihan bedel; health science university antalya training and research hospital, kazım karabekir street postal zip code: 07100, muratpasa, antalya, turkey. phone: +905075641254, fax: +902422494487, email: cihanbedel@hotmail.com and inflammatory parameters, to assist in diagnosis of aa (58). the alvarado score is the first of these systems. it is based on symptoms, and clinical and laboratory results (9). then raja isteri pengiran anak saleha (ripasa) system was developed for patients in asia. in recent years eskelinen, ohmann and tzanakis scores, which added radiological methods such as ultrasound to the scoring systems; clinical and laboratory findings were also followed. these scoring systems aim to reduce na and mortality/morbidity rates by preventing complications (5-10). despite being inexpensive, reproducible and easy-to-use with high success rates, these systems still have not become a part of routine practice. this study aimed to compare the screening performance characteristics of alvarado, eskelinen, ohmann, ripasa and tzanakis scores in predicting the need for appendectomy in aa patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. korkut et al. 2 2. methods 2.1. study design and setting in this prospective cross-sectional study, patients who were admitted to the emergency department of a tertiary hospital (health science university antalya training and research hospital, antalya, turkey) with abdominal pain suspected to aa between may 2, 2019 and december 1, 2019 were evaluated. this study was approved by the ethics committee of the hospital (ethics code: 2019-129). all subjects consented to participate in the study, and the data were recorded by ed physicians. 2.2. participants all cases with abdominal pain suspected to aa, who were referred to ed during the study period, were included using non-probability sampling method. the exclusion criteria were as follows: (a) being under 18 years of age, (b) elective appendectomy, (c) incarcerated or inguinal hernia, (d) nonoperable patients, (e) not accepting hospitalization, and (f ) incomplete data. 2.3. data gathering the following data were recorded for all subjects: complaints at the time of admission, and examination and laboratory findings. significant ultrasonography (us) and abdominal computed tomography (ct) scan findings were also recorded. the following us findings indicated acute appendicitis: (a) non-compressible, (b) >6 mm outer diameter, (c) appendicolith, (d) target appearance in axial section, and (e) periappendiceal inflammation with fat stranding. the following ct findings indicated acute appendicitis: (a) dilated lumen (≥7mm), (b) appendicolith, (c) periappendiceal fluid collection, and (d) inflamed mesoappendix. the obtained data were used to calculate alvarado, tzanakis, ripasa, eskelinen and ohmann scores. all patients underwent appendectomy and were categorized into two groups according to histopathologic diagnosis: positive appendectomy (pa) and negative appendectomy (na). 2.4. evaluated scores alvarado the alvarado system evaluates 8 parameters, which include symptoms, clinical findings and leukocyte count. the highest possible score is 10, and appendectomy is recommended for scores >7 (11). ohmann and eskelinen the ohmann score is also composed of 8 parameters (tenderness in right lower quadrant, rebound tenderness, presence of urinary system complaint, character of pain, relocalization of pain to the right lower quadrant, age, leukocyte count, abdominal rigidity), a score ≥12 indicates aa (12). in figure 1: area under the curve (auc) of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome. addition to these parameters, the eskelinen scoring system also considers the duration of pain and laboratory results. a score >57 indicates aa (13). ripasa and tzanakis tzanakis et al. developed a scoring system consisting of 4 simplified variables and 15 points based on the combination of clinical evaluation, ultrasonography and laboratory parameters. ripasa is a scoring system developed for the asian and middle-eastern population with 15 objective parameters obtained during routine history taking, physical examination, and haematological assessment and urinalysis. a ripasa score >12 and a tzanakis score >8 indicate aa (8, 14). 2.5. statistical analysis the data were analysed using spss version 18.0. descriptive statistics for categorical data are expressed as numbers and percentages, while mean ± standard deviation and median (minimum-maximum) were used to express continuous data based on normal distribution. student’s t-test was used for variables with normal distribution, and mann-whitney utest was used for variables without normal distribution. the screening performance characteristics of the scoring systems were measured. a greater area under the receiver operating characteristic (roc) curve (auc) indicates better diagnostic value. p<0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of studied cases the study included a total of 74 patients with a preliminary aa diagnosis: 42 males (56.8%) and 32 females (43.2%). table 1 shows the baseline characteristics of studied cases. the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e20 table 1: baseline characteristics of studied patients variables values (n=74) age (year) median (min-max) 33 (18-63) mean ± standard deviation 36.68 ± 11.97 gender(n, %) male 42 (56.8) female 32 (43.2) appendectomy findings for aa positive 65 (87.8) negative 9 (12.2) histopathological findings, n (%) acute appendicitis 53 (71.6) perforated appendicitis 7 (9.4) lymphoid hyperplasia 3 (4.0) unusual histopathological findings 2 (2.8) appendix vermiformis 8 (10.8) others 1 (1.4) clinical findings, n (%) sensitivity on lower right quadrant 64 (86.5) defense-rigidity 49 (66.2) rebound 44 (59.5) fever (>37.3◦) 27 (36.5) nausea-vomiting 26 (35.1) laboratory findings wbc count (×103 /mm3 ) 14.12±4.71 neutrophils (×103 /mm3 ) 11.10±4.57 lymphocytes (×103 /mm3 ) 1.95±0.82 c-reactive protein (mg/dl) 24 (0-331) scores, median (min-max) alvarado 7 (2-10) ohmann 13 (4-16) ripasa 10 (4.5-13.5) tzanakis 13 (3-15) eskelinen 51.1 (29.8-67.6) aa: acute appendicitis; wbc: white blood cell; ripasa: raja isteri pengiran anak saleha appendicitis. median age was 33 (range: 18-63) years. the diagnosis was histopathologically confirmed in 65 cases (87.8%). among these, 7 patients (9.4%) had perforated aa and 3 (4.0%) had lymphoid hyperplasia. 9 (12.2%) patients had negative appendectomy, 1 of these (1.4%) being ovarian cyst rupture. the mean white blood cell (wbc) count was 14.12 ± 4.71 ×103/mm3. the median scores of different systems were as follows: alvarado score 7 (2-10); ohmann score 13 (4-16); ripasa score 10 (4.5-13.5); tzanakis score 13 (3-15); eskelinen score 51.1 (29.8-67.6). 3.2. comparing the scores table 2 compares the baseline characteristics as well as scores between cases with negative and positive appendectomy. median age was significantly higher in patients with positive appendectomy (p=0.006). there was no significant difference between patients with positive and negative appendectomy regarding gender (p=0.163). ultrasonography results were not sufficient for diagnosing aa (p = 0.501); however, computed tomography (ct) scans were able to significantly determine aa (p <0.001). median alvarado, tzanakis, ripasa, eskelinen and ohmann scores were significantly higher in patients with positive appendectomy. screening performance characteristics of the studied systems in determining cases with aa are presented in table 3 and figure 1. tzanakis score was able to determine aa better than the other scoring systems, followed by ohmann and alvarado scores, respectively (based on auc). auc, sensitivity, and specificity of tzanakis score in the cut-off value of 8 were 0.965, 84.4%, and 100%, respectively. for ohmann and alvarado scores, these measures were 0.941; 71.9%, 89.9% and 0.938, 60.9%, 89.9%, respectively. tzanakis scoring system had the best screening performance in detection of cases with aa. 4. discussion based on the findings of the present study, tzanakis score has higher sensitivity and specificity in the diagnosis of aa compared to alvarado, ripasa, eskelinen and ohmann scores. the differential diagnosis of aa only requires simple physical and laboratory analyses; however, it is commonly misdiagnosed due to atypical findings. perforation and na rates are still significantly high. the importance of timely and precise diagnosis has led researchers to develop different scoring systems (15). alvarado is the first and most widely used among them (10). it is simple, easy-to-use and can successfully predict aa (16). subraman et al. reported the sensitivity and specificity of alvarado score to be 68% and 86.96%, respectively (17). whereas, elhosseiny et al. found these values to be 65.2% and 100%, respectively (18). we have found the sensitivity and specificity of alvarado scores to be 60.9% and 89.9%, respectively. khan et al. reported na and perforated appendectomy rates to be 15.6% and 7.8%, respectively (19). researchers have been trying to develop better diagnostic methods to decrease these numbers. studies suggest that the ripasa score is more accurate than the alvarado score, especially in eastern societies (18). frountzas et al. studied 2161 cases of aa and found that while the ripasa system was more sensitive, it had a lower specificity than the alvarado system (20). chong et al. studied the ripasa scoring system, and found that it had 97.5% sensitivity, 81.8% specificity and 91.8% diagnostic accuracy (21). we have found that the auc for the ripasa score was slightly lower than the alvarado score (0.893 vs. 0938). the ohmann score is a simple test that can help diagnose patients with suspected aa (22). similarly, the eskelinen score is considerably successful in ruling out the diagnosis of aa (23). erdem et al. found that the sensitivity and specificity of the ohmann and eskelinen scores 96% and 42%, and 100% and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. korkut et al. 4 table 2: comparing the baseline characteristics as well as acute appendicitis scores between cases with positive and negative appendectomy findings variables appendectomy findings p value negative (n=9) positive (n=65) age (years) median (min-max) 27 (19-46) 36 (18-63) 0.006 gender, n (%) male 3 (33.3) 39 (60) 0.163 female 6 (66.7) 26 (40) ultrasonography findings, n (%) negative 5 (55.6) 28 (43.1) 0.501 positive 4 (44.4) 37 (56.9) computed tomography scan findings, n (%) negative 5 (71.4) 2 (3.6) <0.001 positive 2 (28.6) 55 (96.4) laboratory findings wbc count (×103 /mm3 ) 10.38±3.00 14.64±4.69 0.01 neutrophils (×103 /mm3 ) 7.10±2.91 11.66±4.51 0.004 lymphocytes (×103 /mm3 ) 2.60±0.85 1.86±0.78 0.022 c-reactive protein (mg/dl) 9 (0-321) 33 (0-331) <0.001 clinical findings, n (%) sensitivity on lower right quadrant 3 (33.3) 61 (93.8) <0.001 defense guarding 3 (33.3) 46 (70.8) 0.026 rebound 3 (33.3) 41 (63.1) 0.146 fever (>37.3◦) 4 (44.4) 23 (35.4) 0.716 nausea-vomiting 2 (22.2) 24 (36.9) 0.480 scores, median (min-max) alvarado 4 (2-5) 7 (3-10) <0.001 ohmann 8 (4-13) 13.5 (8-16) <0.001 ripasa 6 (4.5-8) 10 (4.5-13.5) <0.001 tzanakis 4 (3-7) 13 (3-15) <0.001 eskelinen 35.1 (33.8-49.2) 53.9 (29.8-67.6) <0.001 wbc: white blood cell; ripasa: raja isteri pengiran anak saleha appendicitis; min: minimum; max: maximum. table 3: screening performance characteristics of different scoring systems in prediction of acute appendicitis in emergency department alvarado ohmann ripasa tzanakis eskelinen tp 40 47 55 56 42 tn 8 8 8 8 7 fp 1 1 1 1 2 fn 25 18 10 9 23 sensitivity 60.9 (48.64-73.35) 71.9 (59.81-82.69) 75 (64.81-86.47) 84.4 (75.34-93.47) 64.1 (51.77-76.08) specificity 89.9 (51.75-99.72) 89.9 (51.75-99.72) 99.72 (51.75-100) 99.88 (51.75-99.72) 78 (39.99-99.19) ppv 97.56 (86.19-99.61) 97.92 (88.04-99.67) 98.04 (88.69-99.69) 98.25 (89.80-99.72) 95.45 (85.93-98.63) npv 24.24 (17.89-31.98) 30.77 (21.98-41.21) 34.78 (24.44-46.80) 47.06 (31.72-62.97) 23.33 (15.86-32.96) plr 5.54 (0.86-35.56) 6.51 (1.02-41.55) 6.92 (1.09-44.15) 7.75 (1.22-49.24) 2.91 (0.85-10.00) nlr 0.43 (0.29-0.64) 0.21 (0.20-0.49) 0.26 (0.16-0.43) 0.16 (0.08-0.30) 0.45 (0.28-0.73) auc 0.93 (0.87-0.99) 0.94 (0.88-1.00) 0.89 (0.81-0.97) 0.96 (0.90-1.00) 0.86 (0.77-0.97) data are presented with 95% confidence interval (ci). measures are calculated in cut-offs: ≥8 for alvarado score; ≥12 for ohmann score; ≥12 for ripasa score; ≥8 for tzanakis score; ≥57 for eskelinen score. 44%, respectively (24). we found that ohmann and eskelinen scores failed to diagnose aa, but they were sufficiently specific. the eskelinen score is at a disadvantage due to its decimal calculations that make it less practical. it also may require additional diagnostic methods, such as laboratory testing or ultrasonography, for differential diagnosis. the tzanakis score was suggested as a combined clinical evaluation of us results and inflammatory markers, the highest possible score is 15, and ≥8 indicates aa. the sensitivity and specificity were 95.4% and 97.4%, respectively (25). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e20 sigdel et al. reported that the tzanakis score was as effective as the alvarado score, with a lower false-negative rate (26). studies show sensitivity levels to be between 85-96%, but sigdel et al. attribute these low rates to differences in the experience levels of radiologists that perform us (26, 27). 5. limitation the limitations of our study are as follows: (a) the relatively small sample size despite the prospective nature of the study, and (b) different physicians deciding for appendectomy for different cases. further prospective studies with larger sample sizes are required to support our findings. 6. conclusion tzanakis score has higher sensitivity and specificity in diagnosis of aa compared to alvarado, ripasa, eskelinen and ohmann scores. 7. declarations 7.1. acknowledgements the author would like to thank md. aysegul korkut for helping in preparation of this paper. 7.2. author contribution all the authors made a substantial contribution in study design, data interpretation and writing and reviewing the manuscript. authors orcids mustafa korkut: 0000-0003-1665-1601 cihan bedel: 0000-0002-3823-2929 yusuf karancı: 0000-0003-0230-2187 ali avcı: 0000-0002-7019-1012 murat duyan: 0000-0002-6420-3259 7.3. ethical approval ethics committee approval was received for this study. 7.4. funding/support no funding and support was received for this study. 7.5. conflict of interest the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this 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24. erdem h, cetinkunar s, das k, reyhan e, deger c, aziret m, et al. alvarado, eskelinen, ohhmann and raja isteri pengiran anak saleha appendicitis scores for diagnosis of acute appendicitis. world journal of gastroenterology: wjg. 2013;19(47):9057. 25. malla b, batajoo h. comparison of tzanakis score vs alvarado score in the effective diagnosis of acute appendicitis. kathmandu university medical journal. 2014;12(1):48-50. 26. sigdel g, lakhey p, misra p. tzanakis score vs alvarado in acute appendicitis. journal of nepal medical association. 2010;49(178). 27. umar mm, abubakar iu, agbo sp. comparative study of alvarado score and its modifications in the preoperative diagnosis of acute appendicitis at a tertiary center in sokoto, nigeria. nigerian journal of surgery. 2020;26(1):16. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e8 or i g i n a l re s e a rc h accuracy of neck stiffness, kernig, brudzinski, and jolt accentuation of headache signs in early detection of meningitis alireza ala1, farzad rahmani2∗, sima abdollahi1, zahra parsian1 1. emergency medicine research team, tabriz university of medical sciences, tabriz, iran. 2. road traffic injury research center, tabriz university of medical sciences, tabriz, iran. received: august 2017; accepted: december 2017; published online: 20 january 2018 abstract: introduction: the diagnostic value of clinical signs in early diagnosis of meningitis has been evaluated but the existing results are contradicting. the present study aimed to evaluate the accuracy of kernig, brudzinski, neck stiffness, and jolt accentuation of headache ( jah) signs in this regard. methods: in this diagnostic accuracy study, patients with suspected meningitis who were referred to the emergency department were examined regarding presence or absence of the mentioned clinical signs and screening performance characteristics of the signs were calculated. cerebrospinal fluid analysis was used as the reference test. results: 120 cases with mean age of 48.79 ± 21.68 years (18 – 93) were studied (63.3% male). diagnosis of meningitis was confirmed for 45 (37.5%) cases. neck stiffness (p < 0.001), kernig (p < 0.001), brudzinski (p < 0.001), and jah (p < 0.001) had significantly higher frequency among patients with meningitis. the accuracy of neck stiffness, kernig, brudzinski, and jah signs in early detection of meningitis were 0.676 (95% ci: 0.575-0.776), 0.667 (95% ci: 0.552-0.782), 0.720 (95% ci: 0.619-0.821), 0.749 (95% ci: 0.659-839), respectively. conclusion: it seems that diagnostic value of jah is higher than other clinical signs but the accuracy of all signs is in poor to fair range. jah had the highest sensitivity and kernig and brudzinski had the highest specificity. keywords: meningitis; physical examination; headache disorders, secondary; neurologic manifestations © copyright (2018) shahid beheshti university of medical sciences cite this article as: ala a, rahmani f, abdollahi s, parsian z. accuracy of neck stiffness, kernig, brudzinski, and jolt accentuation of headache signs in early detection of meningitis. emergency. 2018; 6(1): e8. 1. introduction b acterial meningitis is a prevalent disease, and its incidence in the united states is 5 to 10 cases for every 1000 population annually. this disease is particularly common amongst men (1). as a cause of mortality and morbidity, meningitis is one of 10 most fatal diseases, and results in 135000 annual deaths (2). it is estimated that 25% of adults with bacterial meningitis and about one third of patients with tuberculosis meningitis die in spite of appropriate antibiotic treatment. one fourth of the patients who survive, suffer from constant or temporary neurologic side effects that can influence their quality ∗corresponding author: farzad rahmani; emergency medicine department, sina medical research and training hospital, tabriz, iran. tel: 00984135498144, fax: 00984135412151 email: rahmanif@tbzmed.ac.ir of life in the future (3). considering the dire consequences of meningitis, its diagnosis is important. rapid and accurate evaluation of the probability of meningitis is necessary, as delayed antibiotic treatment has negative effects on the course of the disease, and can culminate in non-compensable effects on central nervous system (4-6). definite diagnose is made by performing lp and analyzing cerebrospinal fluid (csf), but this method is relatively invasive (6). therefore, evaluation is usually initiated by physical examination and checking for presence or absence of some clinical signs such as kernig, brudzinski and neck stiffness. another clinical sign for early diagnosis of meningitis is jolt accentuation of headache ( jah). checking for this sign, the patient is asked to turn his head horizontally with frequency of 2-3 times in a second, and it is considered positive if the patient’s basic headache accentuated with this maneuver (7). the diagnostic value of the mentioned clinical signs in early diagnosis of meningitis has been evaluated in some studies this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. ala et al. 2 but not only there is not complete information, but also the few existing results are contrary to each other (8-10). based on the above-mentioned points, the present study aimed to evaluate the accuracy of kernig, brudzinski, neck stiffness, and jah signs in early detection of patients suspected to having meningitis. 2. methods: 2.1. study design and setting in this diagnostic accuracy study, patients with suspected meningitis who visited the emergency department (ed) of imam reza hospital of tabriz, iran, during a 15-month period ( june 2015 to august 2016) were studied. tabriz imam reza hospital is a general hospital that is affiliated to tabriz university of medical sciences, and the admission rate of the emergency department of this hospital is 110000 annually. written consent was taken from the patients prior to entering the study. it was explained to the patients that all of the performed tests were according to existing guidelines, and the patients won’t be deprived from routine treatments. this study was approved by the ethics committee of tabriz university of medical sciences on 08.06.2015 under the number tbzmed.rec.1394.269. 2.2. participants inclusion criteria were: age higher than 18, body temperature higher than 37 centigrade degrees, neck stiffness, and new onset headache. patients with decreased level of consciousness due to any reason, patients who didn’t cooperate enough or were not able to perform the test, such as patients with vertebra osteoarthritis, muscle weakness, focal neurologic deficit and mental retardation were excluded from the study. sampling strategy was convenient sampling. 2.3. data gathering for all of the patients with suspected meningitis, demographic data (age, sex), vital signs, and presence of neck stiffness, kernig, brudzinski and jah signs were documented. then lp was performed and csf was sent to the laboratory for analysis. in addition, a sample of csf was sent for culture and another for pcr. the results of laboratory assays and physical examination were written in the pertaining checklist. physical examination and lp were performed by a senior resident of emergency medicine under the supervision of the attending emergency medicine physician. laboratory reported the results without knowing the findings of physical examination. interpreting laboratory data was done by an expert emergency physician. 2.4. definitions – suspected meningitis cases were identified as patients with body temperature higher than 37 centigrade degrees, neck stiffness, and new onset headache. – existence of 5 or more white blood cells in each power field of csf sample microscopy and csf protein more than 45 mg/dl was considered positive for meningitis diagnosis (3, 11). 2.5. statistical analysis the sample size was calculated to be 98 using lin naing software, considering 95% confidence level (ci), 80% power,79% sensitivity, 82% specificity, and 12 unit difference in reported sensitivity (12). data were analyzed by spss 17.0. descriptive statistical methods (frequency, percentage, mean ± standard deviation) were used for describing the data. kolmogorov– smirnov test was used to evaluate normal distribution of the data. p value less than 0.05 was considered significant in this study. screening performance characteristics (sensitivity, specificity, positive and negative like hood ratios (lr), positive and negative predictive values) of jah test in diagnosis of meningitis were calculated (using vassarstats medical calculator) and receiver operating characteristic (roc) curve and area under the curve (auc) were used to measure its diagnostic accuracy. csf analysis was considered as the reference test. auc 90 -100 was considered as excellent accuracy, 80 -90 as figure 1: area under the receiver operating characteristic (roc) curve of neck stiffness (0.676), kerning (0.667), brudzinski (0.720), and jolt accentuation of headache (0.749) signs for diagnosis of meningitis in emergency department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e8 table 1: demographic features, presenting vital signs, clinical signs and cerebrospinal fluid (csf) analysis of the studied patients variables diagnosis of meningitis p yes (n=45) no (n=75) age (year) 42.71±21.64 52.44±21.01 0.017 sex male/female ratio 29/16 47/28 1.000 vital signs temperature (celsius) 38.44±0.63 37.84±0.57 <0.001 heart rate (/minute) 87.33±11.13 81.92±10.45 0.008 respiratory rate (/minute) 16.00±2.41 15.39±1.93 0.128 mean arterial pressure (mmhg) 86.07±12.71 91.72±14.76 0.035 clinical signs neck stiffness 29 (64.4) 22 (29.3) <0.001 kernig sign 25 (55.6) 8 (10.7) <0.001 brudzinski sign 24 (53.3) 7 (9.3) <0.001 jolt accentuation of headache 38 (84.7) 26 (34.7) <0.001 csf analysis white blood cells (/mm3) 624.38±1987.38 0.39±1.04 0.007 protein (mg/dl) 78.00±54.93 42.03±27.44 <0.001 glucose (mg/dl) 64.76±37.24 77.87±32.78 0.046 data were presented as mean ± standard deviation or frequency (%). table 2: screening performance characteristics of different clinical signs for diagnosis of meningitis in emergency department characteristics neck stiffness kernig brudzinski jah true positive 29 25 24 38 false positive 22 8 7 26 true negative 53 67 68 49 false negative 16 20 21 7 sensitivity 64.4 (48.7-77.7) 55.5 (40.1-70.0) 53.3 (38.0-68.1) 84.4 (69.9-93.0) specificity 70.6 (58.8-80.3) 89.3 (79.5-94.9) 90.6 (81.1-95.8) 65.3 (53.4-75.7) ppv 56.8 (42.3-70.3) 75.7 (57.4-88.3) 77.4 (58.5-89.7) 59.3 (46.4-71.2) npv 76.8 (64.8-85.7) 77.0 (66.5-85.1) 76.4 (66.0-84.5) 87.5 (75.3-94.4) plr 1.3 (0.88-0.95) 3.12 (1.65-5.88) 3.42 (1.73-6.76) 1.46 (1.02-2.09) nlr 0.30 (0.19-0.46) 0.29 (0.20-0.44) 0.30 (0.21-0.45) 0.14 (0.07-0.28) j point 0.35 0.45 0.44 0.41 jah: jolt accentuation of headache. ppv: positive predictive value, npv: negative predictive value, plr: positive likelihood ration, nlr: negative likelihood ratio. good, 70 80 as fair, 60 70 as poor, and 50 60 as fail. 3. results 184 patients entered the study, but 36 were eliminated from the study owing to meeting any exclusion criterion and 34 were also omitted on the grounds of lacking necessary cooperation and inaccessibility to the final diagnosis. finally, 120 cases with suspected meningitis and mean age of 48.79± 21.68 years (18 – 93) were studied (63.3% male). diagnosis of meningitis (csf wbc>5/mm3 and csf protein>45mg/dl) was confirmed for 45 (37.5%) cases. table 1 shows the demographics, vital and clinical signs, and csf analysis of the studied patients. neck stiffness (p < 0.001), kernig (p < 0.001), brudzinski (p < 0.001), and jah (p < 0.001) had a significantly higher frequency among patients with meningitis. screening performance characteristics of the mentioned clinical signs are shown in table 2 and figure 2. the area under the roc curve of neck stiffness, kernig, brudzinski, and jah signs were 0.676 (95% ci: 0.575-0.776), 0.667 (95% ci: 0.552-0.782), 0.720 (95% ci: 0.619-0.821), 0.749 (95% ci: 0.659-839), respectively. 4. discussion the findings of the current study showed that diagnostic value of jah in diagnosis of meningitis in emergency department is higher than other clinical signs such as kernig, brudzinski and neck stiffness but the accuracy of all the mentioned signs is in poor to fair range (auc 60 to 80). jah had the highest sensitivity (84.4%) and kernig and brudzinski had the highest specificity (89.3% and 90.6%, respectively) among this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. ala et al. 4 the evaluated signs. in the study by uchihara et al. that evaluated jah test for the first time, sensitivity and specificity of the test were 97% and 60%, respectively (7). according to another study, which was performed by aminzadeh et al. on 14 patients the sensitivity, specificity, positive predictive value, negative predictive value, positive and negative like hood ratio of jah test were 100, 71, 78, 100, 1 and zero, respectively (11). in the study by nakao and et al. sensitivity of neck stiffness, kernig, brudzinski and jah test for pleocytosis in csf analysis were 13%, 2%, 2% and 21%, respectively, which were significantly lower than our findings, but the difference between the sensitivities of the tests were almost similar to our study and the sensitivity of jah was higher than other clinical signs. the specificity of neck stiffness, kernig, brudzinski and jah test in that study were 97, 98, 80 and 82 percent, respectively (13). in the study by tamune and et al. the sensitivity and specificity of jah test were 63 and 43, respectively. contrary to our study, in their study patients with altered mental status were also evaluated (6). considering the results of the present and other studies absence of classic signs of meningitis is not enough for ruling out meningitis. since the overall accuracy of jah and other clinical signs is in poor to fair range, they do not have good performance alone in detection of meningitis. it seems that physicians should not solely rely on a single test or sign, and they should consider a collection of clinical signs and symptoms and history to have a better judgment. a lot of retrospective and prospective studies have shown that diagnosis of meningitis should be made according to the results of physical examination, history and csf analysis (5, 7, 14, 15). 5. limitation small sample size and excluding the patients with lowered level of consciousness and cervical vertebral problems were some limitations of our study. 6. conclusion the findings of the current study showed that diagnostic value of jah in diagnosis of meningitis in emergency department is higher than other clinical signs such as kernig, brudzinski and neck stiffness, but the accuracy of all the mentioned signs is in poor to fair range. jah had the highest sensitivity and kernig and brudzinski had the highest specificity among the mentioned clinical signs. 7. appendix 7.1. acknowledgements the authors are grateful to all the health staff and patients who participated in the study. this article is based on a dataset forming part of sima abdollahi’s m.d thesis, entitled “diagnostic value of jolt accentuation of headache for diagnosis of meningitis in patients referred to emergency department”. it is registered at tabriz university of medical sciences (no: 93/3-9/17) and was presented and defended in jan 2016. 7.2. author contribution all authors have read and approved the manuscript. rahmani and alireza ala performed data collection, literature review, and drafting of the manuscript. sima abdollahi and zahra parsian undertook designing major parts of the study and performed the statistical analysis. 7.3. funding/support this article is not supported by any funding organization. there is no sponsor for this work. 7.4. conflict of interest the authors declare that they have no competing interests references 1. meurer wj. central nervous system infections. in: walls mh, editor. rosen’s emergency medicine, cocenpts and clinical practice. 8 ed. sanders: elsevier inc 2014. p. 144759. 2. fitch mt, beek d. emergency diagnosis and treatment of adult meningitis. lancet infect dis. 2007;7:191-200. 3. waghhare s, kalantri a, joshi r, kalantri s. accuracy of physical signs for detecting meningitis: a hospital based diagnostic accuracy 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review. medicine (baltimore). 2000;79:360-8. 15. riordan fa, thomson ap, sills ja, hart ca. who spots the spots? diagnosis and treatment of early meningococcal disease in children. bmj. 1996;313:1255-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods: results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e31 or i g i n a l re s e a rc h full and modified glasgow-blatchford bleeding score in predicting the outcome of patients with acute upper gastrointestinal bleeding; a diagnostic accuracy study ali shahrami1, saba ahmadi1∗, saeed safari2 1. emergency department, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran. 2. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: april 2018; accepted: may 2018; published online: 17 may 2018 abstract: introduction: screening of high risk patients and accelerating their treatment measures can reduce the burden of the disease caused by acute upper gastrointestinal (gi) bleeding. this study aimed to compare the full and modified glasgow-blatchford bleeding score (gbs and mgbs) in prediction of in-hospital outcomes of upper gi bleeding. methods: in the present retrospective cross-sectional study, the accuracy of gbs and mgbs models were compared in predicting the outcome of patients over 18 years of age with acute upper gi bleeding confirmed via endoscopy, presenting to the emergency departments of 3 teaching hospitals during 4 years. results: 330 cases with the mean age of 59.07 ± 19.00 years entered the study (63.60% male). area under the curve of gbs and mgbs scoring systems were 0.691 and 0.703, respectively, in prediction of re-bleeding (p = 0.219), 0.562 and 0.563 regarding need for surgery (p = 0.978), 0.549 and 0.542 for endoscopic intervention (p = 0.505), and 0.767 and 0.770 regarding blood transfusion (p = 0.753). area under the roc curve of gbs scoring system regarding need for hospitalization in intensive care unit (0.589 vs. 0.563; p = 0.035) and mortality (0.597 vs. 0.564; p = 0.011) was better but the superiority was not clinically significant. conclusion: gbs and mgbs scoring systems have similar accuracy in prediction of the probability of re-bleeding, need for blood transfusion, surgery and endoscopic intervention, hospitalization in intensive care unit, and mortality of patients with acute upper gi bleeding. keywords: gastrointestinal hemorrhage; decision support techniques; outcome assessment (health care); hospital mortality © copyright (2018) shahid beheshti university of medical sciences cite this article as: a shahrami, ahmadi s, safari s. full and modified glasgow-blatchford bleeding score in predicting the outcome of patients with acute upper gastrointestinal bleeding; a diagnostic accuracy study. emergency. 2018; 6(1): e31. 1. introduction u pper gastrointestinal (gi) bleeding is a common cause of visiting the emergency department with a mean incidence of about 100 individuals in each 100000 population per year (1-3). the rate of mortality in these patients has been estimated to be between 2% to 15% and for cases with re-bleeding this rate rises to 10% to 30% (4, 5). various factors such as age, hemodynamic status, need for blood transfusion, presence of bright blood in vomit or stool, and history of chronic hepatic diseases have been deemed ∗corresponding author: saba ahmadi; emergency department, shohadaye tajrish hospital, shahrdari avenue, tajrish square, tehran, iran. tel: +989126057245 email: ahmadisaba227@yahoo.com related to the prognosis of these patients (6, 7). patients presenting to the emergency department with complaint of upper gi bleeding have a wide range from very low risk to very high risk regarding the risk of re-bleeding and need for surgical and endoscopic interventions. screening of patients with higher risk and accelerating their diagnostic and treatment measures can be a big step towards reducing the burden of the disease, the financial cost, and mortality caused by it. therefore, by understanding this concept, various studies have been performed with the aim of designing and comparing clinical decision rules for scoring of patients regarding the probability of dangerous outcomes occurring (8-10). yet, each of these models has weak and strong points compared to another. one of these clinical decision rules is glasgow-blatchford bleeding score (gbs), the modithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. shahrami et al. 2 fied version of which (mgbs) has been introduced by elimination of qualitative factors. this system has moderate to good accuracy in prediction of outcomes such as probability of re-bleeding and need for interventions like endoscopy, surgery, and blood transfusion (11-13). the preset study has been designed with the aim of comparing the gbs and mgbs in prediction of in-hospital outcomes of patients presenting to emergency department with symptoms of upper gi bleeding. 2. methods 2.1. study design and setting in the present retrospective cross-sectional study, the diagnostic accuracy of gbs and mgbs models in predicting the outcome of patients with acute upper gi bleeding, presenting to the emergency departments of 3 teaching hospitals (imam hossein, shohadaye tajrish, and taleghani), tehran, iran, from spring 2011 to winter 2016 (4 years) were compared. the researchers adhered to the ethical principles of clinical researches and kept patient data confidential. methodology of the study was approved by the ethics committee of shahid beheshti university of medical sciences. 2.2. participants all patients over 18 years of age visiting the mentioned emergency departments with symptoms of upper gi bleeding (hematemesis, coffee ground vomit, melena, hematochezia) whose bleeding was confirmed via endoscopy were included via census sampling method. incomplete medical profile, unavailability of data needed for calculation of score, and the outcome of the patient not being known were among the exclusion criteria. 2.3. data gathering demographic data (age, sex), vital signs on admission (blood pressure, heart rate), clinical symptom on admission (syncope, melena, coffee ground vomit, hematochezia), history of illnesses (gi bleeding, hepatic disease, cardiac disease), history of consuming anti-coagulation drugs or platelet aggregation inhibitors, laboratory findings (hemoglobin and blood urea nitrogen levels), and finally, outcome of the patients were extracted from their clinical profile and gathered using a pre-designed checklist. the evaluated outcomes in the present study included: in-hospital mortality, re-bleeding in the present hospitalization duration, need for blood transfusion, hospitalization in intensive care unit (icu), and need for an intervention, either endoscopic, surgical or radiologic. a senior emergency medicine resident was in charge of extracting and gathering data of the patients from their clinical profiles. blood transfusion in these patients had been done based on the decision of the in-charge appendixl 1: calculation of gbs score variable score heart rate (/min) ≥ 100 1 systolic blood pressure (mmhg) 100 – 109 1 90 99 2 less than 90 3 blood urea nitrogen (mg/dl) 19 – 22.4 2 22.4 – 28 3 28 – 70 4 ≥ 70 6 hemoglobin (male) (gr/dl) 12 – 13 1 10 – 12 3 less than 10 6 hemoglobin (female) (gr/dl) 10 – 12 1 less than 10 6 history of chronic disease hepatic 2 cardiac 2 symptom melena 1 syncope 2 physician. 2.4. calculating patients’ scores in the 2 mentioned models the method of calculating the scores of the patients based on gbs model is summarized in appendix 1. in mgbs model, only the scores of quantitative variables of gbs model are considered and the scores of the qualitative variables (history of cardiac and hepatic diseases as well as melena and syncope symptoms) are eliminated from calculations. therefore, the ranges of obtainable scores in gbs and mgbs models are 0 to 23 and 0 to 16, respectively. in the present study, the score ranges of (0–3), (4–7), (8–11), and (12–23) were considered as the first to 4th quartiles of gbs system, respectively, and (0–1), (2–6), (7–9), and (10–16) were the first to 4th quartiles of mgbs system, respectively. subsectionstatistical analysis after entering data to a designed excel sheet, they were analyzed using spss 21 and stata 11 statistical software. to report the findings, frequency and percentage or mean ± standard deviation were used. in addition, for evaluating the agreement rate between the 2 models in predicting the patients in need of at least one intervention (endoscopic, surgical, radiologic, or blood transfusion) kappa coefficient was calculated. comparison of the area under the receiver operating characteristic (roc) curve was used for comparing the accuracy of the 2 models in predicting the mentioned outcomes. in this study, the area this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e31 table 1: baseline characteristics of the studied patients variable rates sex male 210 (63.6) female 120 (36.4) age (year) 20 – 39.9 63 (19.1) 40 – 59.9 91 (27.6) > 60 176 (53.3) symptoms on admission systolic blood pressure (mmhg) 107.2 ± 22.8 diastolic blood pressure (mmhg) 71.6 ± 12.4 heart rate (/min) 94.8 ± 16.7 blood hemoglobin (gr/dl) 9.6 ± 2.4 blood urea nitrogen (mg/dl) 37.6 ± 32.5 symptom on admission syncope 47 (14.2) melena 236 (71.5) hematemesis 140 (42.4) coffee ground vomit 59 (17.9) drug history yes 135 (40.9) no 195 (59.1) history of gastrointestinal bleeding yes 77 (23.3) no 253 (76.7) history of cardiac disease yes 101 (30.6) no 229 (69.4) history of hepatic disease yes 7 (2.1) no 323 (97.9) the rates are reported as either frequency (%) or mean ± standard deviation. under the curve of 90-100 was considered as excellent, 80-90 as good, 70-80 as moderate, 60-70 as weak and 50-60 as poor. in all analyses, level of significance was considered to be 0.05. 3. results 3.1. baseline characteristics 400 patients who had presented to the emergency department with complaint of upper gi bleeding were evaluated. 70 (17.5%) cases were excluded from the study due to missing data or lost to follow-up. in the end, 330 individuals with the mean age of 59.07 ± 19.00 (19 – 95) years entered the study (63.60% male). table 1 depicts the baseline characteristics of the studied patients. most of the patients (53.3%) were in the over 60 years age group and their most common symptom on admission to emergency department was melena (71.5%). 3.2. outcomes 178 patients had needed at least one of the interventions of blood transfusion, endoscopy, or surgery. frequency of need for the mentioned interventions was 137 (41.5%) cases of need for blood transfusion, 84 (25.5%) cases of need for endoscopic intervention, and 17 (5.2%) cases of need for surgery (some of the patients needed more than one intervention). none of the patients had undergone radiologic intervention. 49 (14.8%) patients were hospitalized in the icu and 281 (85.2%) were hospitalized in the gastroenterology department. in the end, 90 (27.3%) patients were affected with re-bleeding and 55 (16.7%) patients had died. 3.3. comparing the accuracy of the 2 models mean gbs and mgbs scores of the patients were 9.95 ± 4.22 (0 – 19) and 8.29 ± 3.77 (0 – 16), respectively. table 2 shows the frequency of patients in various quartiles of gbs and mgbs scores and indicates the need for at least 1 intervention in each quartile (kappa = 0.752, p <0.001). there was a significant correlation between higher quartile of both gbs (r = 0.416, p < 0.0001) and mgbs (r = 0.422, p < 0.0001), and increase in need for at least one intervention. area under the curves of gbs and mgbs scoring systems in prediction of re-bleeding (p = 0.219), need for surgery (p = 0.978), endoscopic intervention (p = 0.505), and blood transfusion (p = 0.753) were not significantly different. however, although area under the roc curve of gbs scoring system was significantly higher regarding need for hospitalization in icu (p = 0.035) and mortality (p = 0.011), the difference was not clinically significant. the highest accuracy of both models was in prediction of need for blood transfusion and re-bleeding. 4. discussion based on the present study findings, gbs and mgbs scoring systems have similar accuracy in prediction of the probability of re-bleeding, need for blood transfusion, surgical intervention, and endoscopic intervention in patients with acute upper gi bleeding. regarding prediction of need for hospitalization in icu and in-hospital mortality, although the difference between the 2 models was statistically significant, it was not clinically important. the overall accuracy of the 2 models in predicting the mentioned outcomes was weak and the highest accuracy belonged to predicting the probability of re-bleeding and need for blood transfusion, which were in the moderate range (70-80). stanley et al. in 2011 compared gbs and rockall systems in predicting the outcome of patients with acute upper gi bleeding and pointed out the superiority of gbs system regarding prediction of need for surgery intervention, endoscopy, and blood transfusion (9). balaban et al. in a study titled "predictors for in-hospital mortality and need for clinthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. shahrami et al. 4 table 2: frequency of patients in various quartiles of gbs and mgbs scores and the rate of need for at least 1 intervention in each quartile quartile1 gbs frequency (%) p mgbs frequency (%) p frequency need for intervention2 frequency need for intervention first 31 (9.4) 3 (9.6) 21 (6.4) 1 (4.7) second 50 (15.2) 8 (16.0) 0.0001 73 (22.1) 17 (23.2) 0.0001 third 113 (34.2) 74 (65.4) 85 (25.8) 55 (64.7) fourth 136 (41.2) 93 (68.3) 151 (45.8) 105 (69.6) 1: score ranges of (0 – 3), (4 – 7), (8 – 11), and (12 – 23), were considered as 1st to 4th quartiles of gbs system, respectively, and (0–1), (2–6), (7–9), and (10–16) were considered the first to 4th quartiles of mgbs system, respectively. 2: need for at least one of endoscopic, surgical, and radiologic interventions, and blood transfusion. ical intervention in upper gi bleeding" showed that rockall and blatchford models are good predictors for screening more critically ill patients with weaker outcome (14). comparison of gbs and aims65was also indicative of the superiority of gbs in detection of patients with high risk and those in need of blood transfusion and other interventions (12). laursen et al. in 2012 in a prospective study to compare the scales gbs, egbs, rockall, baylor, and cedars-sinai center index regarding prediction of the need for hospital intervention, 30-day mortality, early discharge, and re-bleeding showed that gbs determines the need for hospital intervention and outpatient visit accurately (15). in contrast, the results of a study on comparison of various scoring systems for patients with non-varicose upper gi bleeding showed that none of the existing systems have proper accuracy in predicting the probability of re-bleeding (16). a one-year prospective cohort in 2012 estimated the efficiency of gbs and mgbs in prediction of patient outcome to be the same (17). the results of a study by quach et al. in 2014 in vietnam was also indicative of the similar efficacy of the 2 mentioned scoring systems in predicting the need for clinical intervention in patients with upper gi bleeding (18). findings of the present study was similar to quach and cheng studies and indicated the similar accuracy of gbs and mgbs systems in predicting outcomes such as need for clinical interventions as well as prediction of mortality and need for blood transfusion. however, in this study, the power of the 2 models in prediction of need for hospitalization in icu was also evaluated, which showed the similar and low accuracy of both models. the overall accuracy of the models in this study was estimated a little lower than previous studies, which might be due to the limitations of this study or the differences in clinical decision-making in the studied hospitals. another reason for the low accuracy of models in the present study might be the type of patients evaluated. in this study, only patients whose bleeding was confirmed via endoscopy and were therefore hospitalized were included and thus, a large number of patients who have probably been discharged from emergency department with a very low or low risk have been eliminated and this factor has affected the screening performance characteristics of the test. it seems that for determining the best clinical decision rule in predicting the outcome of patients with acute upper gi bleeding, more comprehensive studies and performing a systematic review and if possible, a meta-analysis are needed. 5. limitation small sample size, retrospective design, and probability of selection bias might be among the most important limitations of the present study. additionally, since selection of patients in need of intervention in various hospitals was based on the in-charge physician’s opinion and not a determined standard, therefore this may cause errors in selection of patients. 6. conclusion based on the findings of the present study, gbs and mgbs scoring systems have similar accuracy in prediction of the probability of re-bleeding, need for blood transfusion, surgical intervention, and endoscopic intervention in patients with acute upper gi bleeding. regarding prediction of need for hospitalization in icu and in-hospital mortality, although the difference between the 2 models was statistically significant, it was not clinically considerable. the overall accuracy of the 2 models in predicting the mentioned outcomes was weak and the highest accuracy of the models belonged to predicting the probability of re-bleeding and need for blood transfusion, which were in the moderate range (70-80). 7. appendix 7.1. acknowledgements hereby, the authors thank all the staff of medical profile archiving units of the studied hospitals for their cooperation in retrieving the clinical profiles of the patients. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e31 7.2. author contribution all the authors meet the standard criteria of authorship contribution based on the recommendations of the international committee of medical journal editors. 7.3. funding/support no funds have been received. 7.4. conflict of interest there are none. references 1. lassen a, hallas j, de muckadell ob. complicated and uncomplicated peptic ulcers in a danish county 1993– 2002: a population-based cohort study. the american journal of gastroenterology. 2006;101(5):945. 2. van leerdam m, vreeburg e, rauws e, geraedts a, tijssen j, reitsma j, et al. acute upper gi bleeding: did anything change?: time trend analysis of incidence and outcome of acute upper gi bleeding between 1993/1994 and 2000. the american journal of gastroenterology. 2003;98(7):1494-9. 3. targownik le, nabalamba a. trends in management and outcomes of acute nonvariceal upper gastrointestinal bleeding: 1993–2003. clinical gastroenterology and hepatology. 2006;4(12):1459-66. e1. 4. van leerdam m. epidemiology of acute upper gastrointestinal bleeding. best practice & research clinical gastroenterology. 2008;22(2):209-24. 5. tramer mr, moore ra, reynolds djm, mcquay hj. quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic nsaid use. pain. 2000;85(1-2):169-82. 6. lim c, vani d, shah s, everett s, rembacken b. the outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study. endoscopy. 2006;38(06):581-5. 7. kolkman j, meuwissen s. a review on treatment of bleeding peptic ulcer: a collaborative task of gastroenterologist and surgeon. scandinavian journal of gastroenterology. 1996;31(sup218):16-25. 8. camellini l, merighi a, pagnini c, azzolini f, guazzetti s, scarcelli a, et al. comparison of three different risk scoring systems in non-variceal upper gastrointestinal bleeding. digestive and liver disease. 2004;36(4):271-7. 9. stanley aj, dalton hr, blatchford o, ashley d, mowat c, cahill a, et al. multicentre comparison of the glasgow blatchford and rockall scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage. alimentary pharmacology & therapeutics. 2011;34(4):4705. 10. enns ra, gagnon ym, barkun an, armstrong d, gregor jc, fedorak rn, et al. validation of the rockall scoring system for outcomes from non-variceal upper gastrointestinal bleeding in a canadian setting. world journal of gastroenterology: wjg. 2006;12(48):7779. 11. cheng d, lu y, teller t, sekhon h, wu b. a modified glasgow blatchford score improves risk stratification in upper gastrointestinal bleed: a prospective comparison of scoring systems. alimentary pharmacology & therapeutics. 2012;36(8):782-9. 12. yaka e, yilmaz s, ozgur dogan n, pekdemir m. comparison of the glasgow-blatchford and aims65 scoring systems for risk stratification in upper gastrointestinal bleeding in the emergency department. academic emergency medicine. 2015;22(1):22-30. 13. quach dt, dao nh, dinh mc, nguyen ch, ho lx, nguyen n-dt, et al. the performance of a modified glasgow blatchford score in predicting clinical interventions in patients with acute nonvariceal upper gastrointestinal bleeding: a vietnamese prospective multicenter cohort study. gut and liver. 2016;10(3):375. 14. balaban dv, strambu v, florea bg, cazan ar, bratucu m, jinga m. predictors for in-hospital mortality and need for clinical intervention in upper gi bleeding: a 5-year observational study. chirurgia (bucharest, romania : 1990). 2014;109(1):48-54. 15. laursen sb, hansen jm, schaffalitzky de muckadell ob. the glasgow blatchford score is the most accurate assessment of patients with upper gastrointestinal hemorrhage. clinical gastroenterology and hepatology : the official clinical practice journal of the american gastroenterological association. 2012;10(10):1130-5.e1. 16. yang hm, jeon sw, jung jt, lee dw, ha cy, park ks, et al. comparison of scoring systems for nonvariceal upper gastrointestinal bleeding: a multicenter prospective cohort study. journal of gastroenterology and hepatology. 2016;31(1):119-25. 17. cheng dw, lu yw, teller t, sekhon hk, wu bu. a modified glasgow blatchford score improves risk stratification in upper gastrointestinal bleed: a prospective comparison of scoring systems. aliment pharmacol ther. 2012;36(8):782-9. 18. quach dt, dao nh, dinh mc, nguyen ch, ho lx, nguyen nt, et al. the performance of a modified glasgow blatchford score in predicting clinical interventions in patients with acute nonvariceal upper gastrointestinal bleeding: a vietnamese prospective multicenter cohort study. gut liver. 2015. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e60 let ter to editor dividing the emergency department into red, yellow, and green zones to control covid-19 infection; a letter to editor chee-fah chong1,2∗ 1. school of medicine, fu jen catholic university college of medicine, new taipei city, taiwan. 2. emergency department, shin-kong wu ho-su memorial hospital, taipei city, taiwan. received: may 2020; accepted: may 2020; published online: 31 may 2020 abstract: covid-19, in certain respects, can be viewed as a cbrn (chemical, biological, radiological, or nuclear) event due to being a consequence of sars-cov2 virus (the “contaminant”). we, thus, reorganized our emergency department (ed) into 3 distinct zones (red, yellow, and green) for the purpose of infection control. patients with high or medium risk of covid-19 infection are managed in the red zones. low-risk patients are managed in the yellow zones. all patients are prohibited to enter the green zones. green zones are used by healthcare providers (hcps) for personal protective equipment (ppe) donning, inventory, planning, and dining. only hcps who work in the red zones are required to use full level ppe (aerosol precaution). hcps working in the yellow zones require less ppe (contact and droplet precaution). no ppe is required in the green zones. establishing red, yellow, and green zones in the ed can be helpful in reducing cross-infections and minimizing demand for ppe. keywords: coronavirus infections; emergency service, hospital; emergency medical services; health facilities; infection control cite this article as: chong ch-f. dividing the emergency department into red, yellow, and green zones to control covid-19 infection; a letter to editor. arch acad emerg med. 2020; 8(1): e60. dear editor, patients in our emergency department (ed) are divided into 3 groups according to their risk of covid-19 infection. highrisk patients are those with positive tocc (travel history, occupation, contact, cluster) who also have fever or respiratory symptoms. persons under covid-19 investigation (pui) are also considered high-risk. patients without tocc, who have fever or respiratory symptoms, are considered mediumrisk. patients without tocc who have no fever or respiratory symptoms are considered low-risk. covid-19, in certain respects, can be viewed as a cbrn (chemical, biological, radiological, or nuclear) event (1) due to being a consequence of sars-cov2 virus (the “contaminant”). we, thus, reorganized our ed into 3 distinct zones: red, yellow, and green zones (figure 1) for the purpose of infection control. patients with high or medium risk of covid∗corresponding author: chee-fah chong, emergency department, shinkong wu ho-su memorial hospital, no.95, wenchang road, shilin district. taipei city 111, taiwan. tel: 886-2-28332211; fax: 886-2-28353547, email: m002202@ms.skh.org.tw. 19 infection are managed in the red zones. red zones include the outdoor triage tents and the negative-pressure isolation room. low-risk patients are managed in the yellow zones. yellow zones include the indoor triage, waiting room, consultation rooms, observation rooms, and nursing station. green zones are used by healthcare providers (hcps) for personal protective equipment (ppe) donning, inventory, planning, and dining. all patients are prohibited from entering the green zones. our spatial separation strategy using red, yellow, and green zones is also helpful in ppe conservation (2, 3). only hcps who work in the red zones are required to use full level ppe (aerosol precaution: n95 respirator, gown, gloves, eye protection, apron). hcps working in the yellow zones require less ppe (contact and droplet precaution: surgical mask, gown, gloves, eye protection). no ppe is required in the green zones. contaminated ppe should be removed before entering the green zones. in conclusion, establishing red, yellow, and green zones in the ed can be helpful in reducing crossinfections and minimizing demand for ppe. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem ch-f.chong 2 figure 1: planimetric map showing different areas of the emergency department discriminated into red, yellow, and green zones. 1. declarations 1.1. acknowledgements not applicable. 1.2. author’s contribution dr. cf chong brought up the idea and wrote the manuscript. authors orcids chee-fah chong: 0000-0002-3665-8686 1.3. conflict of interest the author (dr. cf chong) has no conflict of interest of any kind. 1.4. funding and support none declared. references 1. ramesh ac, kumar s. triage, monitoring, and treatment of mass casualty events involving chemical, biological, radiological, or nuclear agents. journal of pharmacy and bioallied sciences. 2010;2(3):239-47. 2. brown j, pope c. ppe and possible routes of airborne spread during the covid-19 pandemic. anaesthesia. 2020. 3. verbeek jh, rajamaki b, ijaz s, sauni r, toomey e, blackwood b, et al. personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. cochrane database of systematic reviews. 2020(4):cd011621. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2021; 9(1): e2 https://doi.org/10.22037/aaem.v9i1.993 or i g i n a l re s e a rc h antibody rapid test results in emergency medical services personnel during covid-19 pandemic; a cross sectional study peyman saberian1,2, seyed mohammad mireskandari3, alireza baratloo1,4∗, parisa hasani-sharamin5 †, sepideh babaniamansour6, ehsan aliniagerdroudbari7, mahnaz jamshididana5 1. pre-hospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 2. department of anesthesiology, imam khomeini hospital complex, tehran university of medical sciences, tehran, iran. 3. department of anesthesiology and critical care, tehran university of medical sciences, tehran, iran. 4. department of emergency medicine, sina hospital, tehran university of medical sciences, tehran, iran. 5. tehran emergency medical service center, tehran, iran. 6. school of medicine, islamic azad university of medical sciences, tehran, iran. 7. school of medicine, shahid beheshti university of medical sciences, tehran, iran. received: october 2020; accepted: october 2020; published online: 10 november 2020 abstract: introduction: like other infectious diseases, it is expected that covid-19 will mostly end with the development of neutralizing antibody immunity. this study aimed to evaluate the value of covid-19 antibody rapid test assessment in emergency medical services (ems) personnel. methods: this cross-sectional study was conducted in tehran, iran from 20th march until 20th may 2020. the results of chest computed tomography (ct) scan, and antibody rapid test were compared in ems personnel with confirmed covid-19, as well as symptomatic and asymptomatic ones who had exposure to a probable/confirmed covid-19 teammate. in symptomatic or asymptomatic individuals who were only igm-positive, chest ct scan or rt-pcr was recommended. results: a total of 243 ems personnel with the mean age of 36.14±8.70 (range 21 to 59) years took part in this study (87.7% were males). most of the participants (73.3%) had history of exposure. one hundred sixty-three ems personnel were tested using either rt-pcr test or chest ct-scan or both, and 78 (47.9%) of them had at least one positive result. among the participants who had undergone chest ct-scan and/or rt-pcr test (n=163), 78 had positive chest ct-scan and/or rt-pcr test; of these, 18 individuals had negative results for igm and igg. the rate of positive igm and igg in participants with positive chest ct-scan was 1.6 or 1.3 times more than those with negative chest ct-scan, respectively (p < 0.05). the percentage of positive results for both igm and igg in participants having positive rt-pcr test was 1.7 times more than those having negative rt-pcr test (p < 0.05). conclusion: rapid antibody test could help in diagnosis of covid-19 in asymptomatic or symptomatic ems personnel who did not undergo rt-pcr test or the test was reported as negative. however, its sensitivity could be enhanced through use along with other diagnostic methods. keywords: antibodies; clinical laboratory techniques; covid-19; reagent kits, diagnostic; emergency medical services cite this article as: saberian p, mireskandari s m, baratloo a, hasani-sharamin p, babaniamansour s, aliniagerdroudbari e, jamshididana m. antibody rapid test results in emergency medical services personnel during covid-19 pandemic; a cross sectional study. arch acad emerg med. 2021; 9(1): e2. ∗corresponding author: alireza baratloo; department of emergency medicine, sina hospital, hasanabad square, tehran, iran. tel: +989122884364; email: arbaratloo@sina.tums.ac.ir, orcid: http;//0000-0002-4383-7738. † corresponding author: parisa hasani-sharamin; tehran emergency medical service center, iranshahr street, tehran, iran. tel: +989127099930; email: parisahasaniems@gmail.com, orcid: http;//0000-0003-2942-5275. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 2 1. introduction coronavirus disease (covid-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), became a global health concern. covid-19 is a highly contagious and multifaceted disease, which has infected millions of people worldwide (1, 2). reverse transcription polymerase chain reaction (rt-pcr) was mostly recommended and used in terms of diagnosis of covid-19 (3-6). some specific alterations in lung computed tomography (ct) scan was also highly frequent in covid-19 patients but in some cases, normal lung ct-scan was reported along with positive rt-pcr (7). on the other hand, it should be mentioned that covid19 can cause widely different clinical manifestations, most of which are nonspecific, or be asymptomatic. therefore, the prevalence of covid-19 is mostly underestimated, which may increase the risk of exposure (8, 9). like other infectious diseases, it is expected that covid-19 will mostly end with the development of neutralizing antibody immunity. antibodies are produced within days to weeks after infection with the virus. however, negative results of antibodies in the patients with positive rt-pcr test have been reported for various reasons. the strength of the antibody response depends on various factors, including age, nutritional status, the severity of the disease, and certain medications or infections that suppress the immune system (8-12) . the emergency medical services (ems) personnel are at high risk of infection because of repeated exposures; so they are an appropriate population for the study on covid19 (13). it is vital to investigate the ems personnel both in terms of their immune system and being a carrier for other health providers. since due to the epidemic, it was not possible to perform definitive tests for all people, rapid antibody tests are the most appropriate option to investigate these cases, so this study was designed and conducted with the following four main objectives: 1. assessing the immune system of emergency medical services personnel who were confirmed cases of covid-19 2. assessing the probability of infection and the immune system of emergency medical service personnel who were symptomatic but either had a negative result of covid-19 test or were not tested 3. assessing the probability of infection in asymptomatic personnel with a history of encountering a definite or probable covid-19 case 4. assessing the relationship between ct scan, rt-pcr, and epidemiological issues (symptoms, history of exposure) with the antibody test. 2. methods 2.1. study design and setting this study was a cross-sectional study conducted in tehran, iran. the protocol of the study was approved by the ethics committee of tehran university of medical science (code: ir.tums.vcr.rec.1399.322) and the principles of confidentiality were adhered to. all information was analyzed and reported anonymously. written informed consent was obtained from all patients prior to their participation in the study. this study did not impose any additional cost on participants or the healthcare system, and all costs were paid from the received grant. 2.2. study population from 20th march until 20th may 2020, two groups of ems personnel working for tehran ems center were invited for participation in this study. the ems personnel with any of the below criteria were included: • confirmed covid-19 cases based on the results of rt-pcr test and/or non-enhanced chest ct-scan. • those who had covid-19 symptoms since the onset of the epidemic, and did not undergo any diagnostic test or whose test results were negative. • asymptomatic ones who had exposure to suspected or confirmed covid-19 teammates, and did not undergo diagnostic tests or whose test results were negative. all ems personnel who were unwilling to participate, refused to perform further required paraclinical investigation, and filled out the checklist incompletely, were excluded. 2.3. definitions suspected, confirmed, and symptomatic cases were defined as follows (14-17): suspected case a. a patient who has an acute respiratory illness (has fever and shows at least one sign and/or symptom of respiratory disease, such as cough and shortness of breath), and lives in or has traveled to a covid-19 hotspot within 14 days before the onset of symptom. or b. a patient who has an acute respiratory illness and has had a close encounter with a confirmed or suspected covid-19 case within 14 days before the onset of symptom. or c. a patient who has a severe acute respiratory illness (has fever and shows at least one sign and/or symptom of respiratory disease, such as cough and shortness of breath and needs to be hospitalized) when there are no alternative diagnoses that explain the clinical manifestations. confirmed case a patient with positive result of laboratory test and/or chest this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e2 ct-scan confirmed covid-19, irrespective of clinical signs and symptoms. symptomatic case a person with suspicious signs (based on physical examination) and symptoms of covid-19 (defined as fever, chills, dry cough, shortness of breath, myalgia, diarrhea, loss of sense of smell and taste, chest pain, headache, weakness, or lethargy) who has not undergone any diagnostic tests yet. 2.4. procedure all participants underwent the covid-19 igm/igg rapid test (manufactured by karmaazmaandish co. in tehran, iran). this rapid test is based on immune-chromatography, which is used to detect igm and igg antibodies in the blood and serum (total antibody). a drop of blood (about 20 microliters of serum), lancet, and fingertip are used for blood sampling and then two drops of the buffer are added to the blood. the result is determined in less than 20 minutes. sampling and antibody testing were done outside the laboratory, by two of the investigators with a bachelor’s degree in nursing, in the tehran ems center. for those who had only positive igm, rt-pcr test and chest ct-scan were also performed, to investigate the probability of being an infectious carrier. the covid-19 rt-pcr test is a real-time test that can qualitatively assess the presence of nucleic acids associated with sars-cov-2 in samples (such as nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid-turbinate swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate) obtained from both upper and lower respiratory systems of patients suspected to having covid-19. this modality can be used both for all suspected patients, both those showing symptoms and those who do not have symptoms but have other reasons to suspect covid-19 infection. 2.5. data collection all participants were asked to fill out a 3-part checklist. first part consisted of demographic data and baseline characteristics including age, gender, smoking status, recent history of weight loss, recent history of any infectious disease, history of any vaccination during last year, history of a disease in last five days so that patients were not able to eat anything. second part was about data related to covid-19, including presentation of covid-19 symptoms, history of exposure, having a contaminated teammate or roommate, undergoing related tests of covid-19, number of exposures, time interval between symptom onset and positive rt-pcr test and/or chest ct-scan, and , time interval between symptom onset and positive result of antibody rapid test. third part was about the results of antibody rapid test (only igm positive, only igg positive, both positive, or both negative) and rt-pcr test or chest ct-scan results, if provided. 2.6. statistical analysis the continuous variables were described using mean ± sd and categorical variables were described using frequency and percentage. the normality of distribution was assessed using shapiro-wilks test. the relationship between categorical variables, such as comparing the result of tests, was examined using chi-square or fisher’s exact test. also, we used independent t-test for assessment of mean difference between two groups. p-value<0.05 was considered statistically significant. the sensitivity and specificity of rapid antibody test with 95% confidence interval (ci) was calculated based-on rt-pcr test and chest ct-scan diagnosis, as gold standards. also, accuracy, positive likelihood ratio (plr), negative likelihood ratio (nlr), positive predictive value (ppv ), and negative predictive value (npv ) were calculated for the screening index. the data were analyzed using stata statistical software: release 14 (college station, tx: statacorp lp). 3. results 3.1. baseline characteristics of participants two hundred forty-three ems personnel with the mean age of 36.14±8.70 (range 21 to 59) years took part in this study. the baseline information is shown in table 1. the majority of the participants were male (87.7%) and most of the participants (73.3%) had history of exposure. figure 1 and table 2 show the distribution of symptomatic and asymptomatic cases based on the results of different diagnostic tools. the frequency of positive result of rapid antibody test was higher in participants with history of exposure (43.8%) than those without history of exposure (35.4%) but the difference was not statistically significant (p=0.201) (figure 2). 3.2. symptom onset to performing rapid test the time interval between symptom onset and performing antibody rapid test had a wide range (2 to 83 days). the relationship between the time interval between symptom onset and performing antibody rapid test and the result of chest ct-scan and/or rt-pcr test are shown in table 3. 3.3. relationship between covid-19 diagnostic tools table 4 shows the relationship between the results of performed diagnostic covid-19 tests. the rate of positive igm and igg in participants with positive chest ct-scan were 1.6 or 1.3 times more than that of those with negative chest ctscan, respectively. the rate of igm and/ or igg positive in participants with positive chest ct-scan was 2.5 times higher than those with negative chest ct-scan (p<0.001). the percentage of positive result of both igm and igg in participants this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 4 table 1: baseline characteristics of participants (n=243) variables values sex male 213 (87.7) female 30 (12.3) body mass index mean ± sd 23.4±3.9 history smoking 13 (5.3) recent weight loss 51 (21.0) recent infectious disease 21 (8.6) vaccination in the previous year 48 (19.8) acute disease in the previous five days 10 (4.1) exposure to covid-19 patient suspected 151 (62.1) confirmed 155 (63.8) having contaminated teammate or roommate before getting infected 15(6.2) after getting infected 16 (6.6) presentation symptomatic 122 (50.2) asymptomatic 121 (49.8) chest ct-scan results positive 64 (42.9) negative 85 (57.1) rt-pcr test results (n=101) positive 38 (37.3) negative 63 (63.7) rapid test results only igm positive 3(1.2) only igg positive 19 (7.8) igm and igg positive 79 (32.5) time since symptom onset (day) confirmation by the rt-pcr and/or chest ct-scan 4.2±3.8 confirmation of covid-19 by antibody rapid test 50.6±18.4 data are presented as mean ± standard deviation (sd) or frequency (%); ct: computed tomography; rt-pcr: reverse transcription polymerase chain reaction; covid-19: coronavirus disease. having positive rt-pcr test was 1.7 times more than those having negative rt-pcr test (p=0.019). the sensitivity and specificity of rapid antibody test compared with chest ctscan was 78.1% (95% ci: 66.0 to 87.5) and 68.2% (95% ci: 57.2 to 77.9), respectively. also, the ppv, npv, plr, nlr, and accuracy of rapid antibody test compared with chest ct-scan were 64.9%, 80.6%, 2.5, 0.32, and 72.5%, respectively. the sensitivity and specificity of rapid antibody test compared with rt-pcr test were 71.1% (95% ci: 54.1 to 84.6) and 58.7% (95% ci: 45.6 to 71.0), respectively. also, the ppv, npv, plr, nlr, and accuracy of rapid antibody test compared with rtpcr were 50.9%, 77.1%, 1.7, 0.49, and 63.4%, respectively (table 5). 4. discussion the present study investigated some aspects of paraclinical features of covid-19 in ems personnel. the majority of participants were symptomatic and had history of exposure. the positive result of all three tests was higher in symptomatic participants. being symptomatic was most concordant with the positive result of chest ct-scan and then with the positive result of rt-pcr test or rapid antibody test. a few number of asymptomatic ems personnel had positive rapid antibody test. the positive result of igm and/or igg was significantly higher in participants having positive chest ct-scan. the percentage of positive result of igg or both igm and igg was significantly higher in participants having positive rtpcr test. the result of rapid antibody test was more concordant with the result of chest ct-scan than with the result of rt-pcr test. various studies stated that measuring the level of antibodies is of great value in diagnosing covid-19 (18, 19). the level of igm and igg were increased in the early and late phase of covid-19, respectively. antibody rapid test can be a useful tool for measuring the level of antibodies. investigating the trend of changes in the level of antibodies can help in clinical evaluating of infection (8, 20, 21). in a study of 15 covid19 patients, the positive igm and igg increased from 50% to 81% and 81% to 100% of patients, respectively, within the first to the fifth day after symptom onset (22). long et al. conducted a study on 285 patients, investigating the acute antibody responses to sars-cov-2, and showed that the prevalence of positive virus-specific igg (within 17-19 days after symptom onset) and igm (within 20-22 days after symptom onset) were 100% and 94.1%, respectively (20). sun et al. conducted a study assessing the antibodies in 38 covid-19 patients and the results showed that up to 75% of patients had increased levels of igm and igg, specific to sars-cov-2, in the first week after symptom onset (18). the positive results were higher compared to ours, which may be due to performing a more accurate antibody test in the study of sun et al., which measured the level of igm and igg response against both sars-cov-2 nucleocapsid and spike protein. our study showed a long interval between symptom onset and positive result of igm, which was higher than other studies (20, 23). the reason may be due to the higher number of exposures in ems personnel. our study showed that all three diagnostic tests had high efficacy in detecting covid-19 infection. in a study by zhao et al. conducted on 173 covid-19 patients, the sensitivity of igm, igg, and rt-pcr test were 73.3%, 54.1%, and 54%, respectively during 15 days after symptom onset (21). heydari et al., showed a high proportion (83%) of positive chest ct-scan in diagnosing covid-19 in symptomatic patients (24). however, some studies recommended performthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e2 table 2: the results of performed diagnostic covid-19 tests between symptomatic and asymptomatic ems personnel test participants p-value* symptomatic asymptomatic chest ct-scan positive 60 (61.9) 4 (7.7) <0.001 negative 37 (38.1) 45 (92.3) rt-pcr test positive 34 (50.0) 4 (12.1) 0.001 negative 34 (50.0) 29 (87.9) antibody test only igm positive 1 (0.8) 2 (1.7) only igg positive 15 (12.3) 4 (3.3) <0.001 both positive 64 (52.5) 15 (12.4) both negative 42 (34.4) 100(82.6) data are presented as frequency (%). *ems: emergency medical services; ct: computed tomography; rt-pcr: reverse transcription polymerase chain reaction. table 3: the relationship between the time interval between symptom onset and performing antibody rapid test and the result of chest ctscan and/or rt-pcr test time interval (day) chest ct-scan and/or rt-pcr test positive (n=69) negative (n=31) igm result positive 49.8±16.8 58.0±16.6 negative 45.1±17.8 53.4±18.5 p-value 0.291 0.504 igg result positive 50.1±15.7 54.3±16.3 negative 41.0±20.9 55.3±19.7 p-value 0.074 0.952 data are presented as mean ± standard deviation. ct: computed tomography; rt-pcr: reverse transcription polymerase chain reaction ing the combination of pcr and antibody test for diagnosing the covid-19 patients (19, 21, 22, 25) guo et al. stated that the rate of diagnosis of covid-19 with combination of igm and pcr test (98.6%) was higher than pcr test alone (51.9%) (19). our study stated that adding rapid antibody test decreased false negative cases, especially in asymptomatic ones. in this regard, a study in italy showed that 44% of confirmed cases of covid-19 based on laboratory tests, were asymptomatic (26). some studies had also added serological tests, especially in asymptomatic patients or those with negative rtpcr tests to increase the accuracy of covid-19 detection (19, 20, 22). in this regard, guo et al. conducted a study on 82 confirmed cases (based on positive quantitative pcr) and 58 probable cases (symptomatic patients with negative quantitative pcr) of covid-19. they measured the level of igm and igg and showed that igm and igg were positive in 93.3% and 77.9% of samples, respectively. the positive result of igm was observed in 75.6% and 93.1% of confirmed and probable cases, respectively (19). the lower positive results of antibodies in our study may be due to the shorter period of our study. the stronger association between the results of rapid antibody test and ct-scan compared to the association between rapid antibody test and rt-pcr test may be due to the incorrect sampling of rt-pcr test, different sample types, using low quality and low consistent diagnostic tools, or untimely performance of the tests because the tests are mostly time sensitive (9, 21). early diagnosis of covid-19 in ems personnel is of paramount importance to avoid spread of disease, especially to high-risk patients who receive the most common services of ems. therefore, it is highly recommended to use symptoms and signs, rapid antibody test and other diagnostic methods for ruling out covid-19 and proper training of the ems personnel is also of great value. in this study, eighteen cases whose covid-19 had been confirmed in the previous two months had negative antibody test results. in this regard, the possibility of reinfection with covid-19 should be considered. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. saberian et al. 6 figure 1: (a) veen diagram of positive symptoms related to covid-19 and/or positive result of antibody rapid test in all participants (n=243); (b) veen diagram of positive symptoms related to covid-19 and/or positive result of antibody rapid test and/or positive rt-pcr and/or chest ct-scan in patients in participants who underwent chest ct-scan and/or rt-pcr test (n=163). table 4: the relationship between the results of rapid antibody test with performed diagnostic covid-19 tests rapid test chest ct-scan rt-pcr test positive (n=64) negative (n=85) p positive (n=38) negative (n=63) p igm positive 1(1.6) 0 (0.0) <0.001 0 (0.0) 1 (1.6) <0.019 igg positive 7(10.9) 7 (8.2) 6 (15.8) 4 (6.3) both positive 42(65.6) 20 (23.5) 21 (55.3) 21 (33.3) both negative 14(21.9) 58 (68.2) 11 (28.9) 37 (58.7) note: data are presented as frequency (%). table 5: screening performance characteristics of rapid test based on chest ct-scan and rt-pcr test as gold standards variable chest ct-scan rt-pcr test value (95%ci) value (95%ci) accuracy 72.5 (65.2 79.7) 63.4 (53.8 72.9) sensitivity 78.1 (66.0 87.5) 71.1 (54.1 84.6) specificity 68.2 (57.2 77.9) 58.7 (45.6 71.0) positive likelihood ratio 2.5 (1.8 3.4) 1.7 (1.2 2.5) negative likelihood ratio 0.32 (0.2 0.5) 0.49 (0.3 0.8) positive predictive value 64.9 (53.2 75.5) 50.9 (36.8 64.9) negative predictive value 80.6 (69.5 88.9) 77.1 (62.7 88.0) ct: computed tomography; rt-pcr: reverse transcription polymerase chain reaction; ci: confidence interval. 5. limitation given that the antibody assessment tests of the participants in this study were performed at different time intervals from the onset of their disease, this can affect the accuracy of the tests. some of the participants with positive result of igm on their antibody rapid test did not undergo rt-pcr test or elisa test against medical advice. the interval between performing chest ct-scan and other tests was not consistent among the cases. considering the impossibility of performing serial antibody tests from the first days of the onset of symptoms or exposure, the time since which immunological tests became positive was not clear. the kit of antibody rapid test was not officially approved. to date, there is no approved rapid antibody test in iran and all kits are in the testing phase. however, the rapid tests used in this project have been reviewed in several reputable centers and its sensitivity and specificity have been evaluated as acceptable; but there was no official authorization for these tests. it is better to carry out a study with a large sample size on different this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e2 figure 2: the results of rapid antibody test based on history of exposure with suspected and/or confirmed case. populations and also with approved tests and kits in future studies. 6. conclusion rapid antibody test could help in diagnosis of covid-19 in asymptomatic ems personnel. the positive result of rapid antibody test was more concordant with positive result of chest ct-scan than with positive result of rt-pcr test. our study showed that being symptomatic was most concordant with the positive result of chest ct-scan and then with the positive result of rt-pcr test or rapid antibody test. 7. declarations 7.1. acknowledgements we would like to express our gratitude to the pre-hospital and hospital emergency research center affiliated to tehran university of medical sciences. 7.2. author contribution the conception and design of the work by ps, phs, smm and ab; data acquisition by phs and mj; analysis and interpretation of data by phs, sb, ea and ab; drafting the work by sb, ea and mj; revising it critically for important intellectual content by ps, phs, smm and ab; all the authors approved the final version to be published; and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work will be answered. 7.3. funding/support this study was funded with a grant received from tehran ems center. 7.4. conflict of interest none declared. references 1. kalkeri r, goebel s, sharma gd. sars-cov-2 shedding from asymptomatic patients: contribution of potential extrapulmonary tissue reservoirs. the american journal of tropical medicine and hygiene. 2020;103(1):18-21. this open-access 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b, deng h, wu g, deng k, chen y, et al. antibody responses to sars-cov-2 in patients with covid19. nature medicine. 2020;26(6):845-8. 21. zhao j, yuan q, wang h, liu w, liao x, su y, et al. antibody responses to sars-cov-2 in patients of novel coronavirus disease 2019. clinical infectious diseases : an official publication of the infectious diseases society of america. 2020:ciaa344. 22. zhang w, du rh, li b, zheng xs, yang xl, hu b, et al. molecular and serological investigation of 2019-ncov infected patients: implication of multiple shedding routes. emerging microbes & infections. 2020;9(1):386-9. 23. hoffman t, nissen k, krambrich j, rönnberg b, akaberi d, esmaeilzadeh m, et al. evaluation of a covid-19 igm and igg rapid test; an efficient tool for assessment of past exposure to sars-cov-2. infection ecology & epidemiology. 2020;10(1):1754538. 24. heydari k, rismantab s, shamshirian a, lotfi p, shadmehri n, houshmand p, et al. clinical and paraclinical characteristics of covid-19 patients: a systematic review and meta-analysis. medrxiv : the preprint server for health sciences. 2020:preprint (doi: 10.1101/2020.03.26.20044057). 25. to kk, tsang ot, leung ws, tam ar, wu tc, lung dc, et al. temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by sars-cov-2: an observational cohort this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2021; 9(1): e2 study. the lancet infectious diseases. 2020;20(5):565-74. 26. european centre for disease prevention and control. novel coronavirus disease 2019 (covid-19) pandemic: increased transmission in the eu/eea and the uk – sixth update 2020 [available from: european centre for disease prevention and control (ecdc). novel coronavirus disease 2019 (covid-19) pandemic: increased transmission in the eu/eea and the uk – sixth update [internet]. stockholm, sweden; 2020. [available from: https://www.ecdc.europa.eu/sites/default/files/docume nts/rra-sixth-updateoutbreak-of-novel-coronavirusdisease-2019-covid -19.pdf ]. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2018; 6 (1): e29 ca s e re p o rt post-traumatic pulmonary pseudocyst following blunt chest trauma; a case report nasim ghafourian1, fatemeh mahdizadeh1∗, mina zavareh2, mitra ahmadi2, mohammad hossein askarzadeh3, fatemeh jalili4 1. department of emergency medicine, imam khomeini hospital, ilam university of medical sciences, ilam, iran. 2. department of emergency medicine, pastornou hospital, tehran, iran. 3. department of emergency medicine, afshar educational hospital, yazd university of medical sciences, yazd, iran. 4. department of emergency medicine, hasheminejad hospital, mashhad university of medical sciences, mashhad, iran. received: april 2018; accepted: may 2018; published online: 1 may 2018 abstract: traumatic pulmonary pseudocyst is a rare complication of chest trauma that has been poorly documented and usually resolves without specific treatment. here, we present a case of pulmonary pseudocyst in a child with chest trauma without obvious symptoms. it is important to consider this diagnosis in patients with chest trauma to avoid unnecessary invasive procedures. keywords: thoracic injuries; contusions; wounds, nonpenetrating; chest trauma; pulmonary pseudocyst; pulmonary contusion © copyright (2018) shahid beheshti university of medical sciences cite this article as: ghafourian n, mahdizadeh f, zavareh m, ahmadi m, askarzadeh m, jalili f. post-traumatic pulmonary pseudocyst following blunt chest trauma; a case report. emergency. 2018; 6 (1): e29. 1. introduction traumatic pulmonary pseudocyst (tpp) is a rare complication of chest trauma that has been poorly documented and rarely talked about (1, 2). it can occur at any age, but is more often seen in children and young adults (3-5). these patients may be asymptomatic with unremarkable examination findings (5, 6). this report presents a case of pulmonary pseudocyst in a child with chest trauma without obvious symptoms. 2. case report a 16 month boy was brought to the emergency department who was run over by a car. his mother explained that the child’s chest was trapped under the rear of a reversing car. on arrival, he was uncomfortable and during examination was irritable. on physical examination, he was hemodynamically stable and well perfused but oxygen saturation was %85 in room air. the physical examination was unremarkable. ∗corresponding author: fatemeh mahdizadeh; department of emergency medicine, imam khomeini hospital, ilam, iran. tel: +989125497734 email: mahdizadeh_fatemeh@yahoo.com there wasn’t significant respiratory distress or any bruising or laceration on chest wall. chest was clear to auscultation. no other abnormalities were noted in the remainder of the physical examination. the patient was in usual state of health prior to the accident. his past history and family history were normal and he was not on any medication. his growth and development were also normal. no evidence of free fluid was found in focused assessment sonography of trauma that was performed by an emergency medicine specialist. a chest x-ray was done in supine position in the emergency department, which was subsequently followed by computed tomography (ct) scan of the chest (figure 1). chest radiography showed bilateral homogenous opacity. ct scan of the chest revealed bilateral parenchymal contusion, low-percentage pneumothorax, a rib fracture, and an oval cavity lesion with an air-fluid level in the basal segment in lower lobe of the right lung. this sub-pleural cavity measured 28 mm (height) and 14 mm (width) in size. there weren’t any pathologic findings in spiral brain ct scan. total leukocyte counts were mildly raised (12900 per mm3 with %64 polymorphonuclear leukocytes). no biochemical abnormalities were revealed. there was no weight loss, lymphadenopathy or clubbing of fingers. he had no known exposure to tuberculosis and no known pulmonary disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. ghafourian et al. 2 figure 1: anterior posterior chest radiograph (left) and axial chest computed tomography (right) at the time of admission. figure 2: anterior posterior chest radiograph on day 3. there was no associated cough, fever, expectoration, hemoptysis or breathlessness, which clinically ruled out an infective process. with no evidence of underlying infection and given the clinical scenario, the diagnosis of tpp was made. pulse oximetry of the patient was monitored continuously. he was treated with oxygen via inhalation (3 liters per minute) and a general surgeon was consulted. oxygen saturation was %97 while receiving oxygen. the patient was moved to the intensive care unit. he was observed. he was comfortable with no new problem. on the third hospital day the chest radiograph showed appreciable reduction in contusion without pneumothorax or significant cavity (figure 2). the patient remained asymptomatic during the hospital stay so he was discharged from the hospital on the next day without any antibiotics, emergency intervention, and additional surgical processes, thus confirmed our diagnosis of tpp. surgeon advised his mother to follow up in clinic. there was no problem after one month. 3. discussion the incidence of tpp has been reported as approximately 3% after blunt chest injuries and was higher in younger patients and usually occurred following high speed motor vehicle accidents or fall. it has also been reported after penetrating chest injury (6-10). in iran, one case that presented with multiple bilateral cysts has been reported (2). tpp manifestations with minor clinical and major radiological signs like the case of this study have been recorded in the literature. patients may be asymptomatic or associated with hemoptysis, cough, dyspnea, chest pain, fever and mild leukocytosis usually within the first 24 hours or up to fourteen days after injury (4-6). physical examination findings are unremarkable and are usually restricted to crackles on the affected chest (5). tpps are air-filled or fluid-filled cavities with no true epithelial lining and their size ranges from 2 to 14 cm in diameter (4, 10). most reported cases of tpps have had concurrent lung injuries such as pulmonary contusion, hematoma, hemopneumothorax, and pneumothorax (5). two mechanisms have been suggested for tpp formation: compression and decompression result in barotraumas and ruptured parenchyma. retraction of normal elastic lung tisthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e29 sue from contusion forms cavities filled with air and/or fluid. also, air from a compressed part of the lung cannot escape fast enough due to closure of the glottis or an obstructed bronchus. higher chest wall compliance and elasticity in children and young adults leads to increased transmission of forces and formation of tpp (9-11). diagnosis is made based on radiographic features and a history of chest trauma. tpp typically follows a benign clinical course and is treated conservatively (12). tpps may be identifiable on chest radiography but ct is more valuable for early diagnosis (9). they may be single or multiple and unilateral or bilateral. they may be seen on the site of injury or on the opposite side secondary to counter coup effects, which are usually sub-pleural lesions commonly found in the lower lobes. unlike other cystic lesions and cavities, the size, shape, and nature of wall of tpps change relatively quickly (13-15). in this case, the cavity was approximately 3 cm and had an air-fluid level. differential diagnoses include post pneumonia carcinoma, pneumatocele, tuberculosis, lung abscess, bronchogenic cysts and pulmonary sequestration. most of these lesions are self-limiting and benign lesions that don’t require specific treatment, yet the clinical course might be complicated due to infection and bleeding (10, 16). surgical intervention is recommended only when complications such as infection, bleeding and rupture develop (12). tpps mostly need conservative management unless complications arise. the use of antibiotics is controversial and not routine (4, 6). resolution usually occurs within a few weeks to a few months. if the cavity lesion does not decrease with time other etiologies must be considered. this patient was treated conservatively without antibiotic therapy. he was asymptomatic and was discharged on day 4 of hospitalization without complications and thus confirmed our diagnosis of tpp. 4. conclusion: tpp is an uncommon complication of chest trauma. often no specific treatment is needed. tpp should be considered in the differential diagnosis of cystic or cavitary lung lesions following significant blunt trauma, particularly in younger patients, to prevent unnecessary and invasive procedures. 5. appendix 5.1. acknowledgements the authors would like to thank the emergency ward staff. 5.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest none. 5.4. funding none. references 1. cho hj, jeon yb, ma ds, lee jn, chung m. traumatic pulmonary pseudocysts after blunt chest trauma: prevalence, mechanisms of injury, and computed tomography findings. journal of trauma and acute care surgery. 2015;79(3):425-30. 2. rahimi-rad m, mohammadi a. multiple bilateral traumatic pulmonary pseuodocysts in a 53 year-old male diagnosed retrospectively. pneumologia (bucharest, romania). 2010;59(2):84-6. 3. das s, cherian s, bisen n, hamarneh w, lenox r. pulmonary cystic lesions post motor vehicle accident: a rare occurrence. qjm: an international journal of medicine. 2012;106(6):581-2. 4. gupta n, george j, gupta rc, dixit r. traumatic pulmonary pseudocyst. international journal of critical illness and injury science. 2013;3(2):155. 5. de dios jaa, paoletti l, bandyopadhyay t. an unusual cystic lung lesion. chest. 2008;134(4):32c. 6. yazkan r, ozpolat b, åd̄ahinalp as. diagnosis and management of post-traumatic pulmonary pseudocyst. respiratory care. 2009;54(4):538-41. 7. fagkrezos d, giannila m, maniatis p, papailiou j, triantopoulou c. post-traumatic pulmonary pseudocyst with hemopneumothorax following blunt chest trauma: a case report. journal of medical case reports. 2012;6(1):356. 8. el-hag-aly ma, allam hk. fate of traumatic pulmonary pseudocyst: factors of resolution. asian cardiovascular and thoracic annals. 2015;23(2):176-9. 9. cheung n, james a, kumar r. large traumatic pneumatocele in a 2-year-old child. case reports in pediatrics. 2013;2013. 10. cherian sv, das s, basu bd, geethakumari pr. traumatic pulmonary pseudocyst. internal medicine. 2013;52(12):1429-30. 11. ahmad z, pandey d, hasan a, anis a. trauma: an unusual aetiology of pulmonary pseudocyst. indian journal of chest diseases and allied sciences. 2008;50(3):293. 12. yang p-j, tsai i-t, liu t-h. traumatic pulmonary pseudocyst. the journal of pediatrics. 2015;167(3):777-. e1. 13. luo l, yin l, liu z, xiang z. posttraumatic pulmonary pseudocyst: computed tomography findings and manthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com n. ghafourian et al. 4 agement in 33 patients. journal of trauma and acute care surgery. 2012;73(5):1225-8. 14. weihua z, yanhong t, hongwei l, qiong l, dihong w. traumatic pulmonary cyst in 6 cases of ct performance analysis. journal of yangtze university (natural science edition). 2012;11:011. 15. ding c-q, sun y-y, ding a-l, zhang y-n, wang ws, wang c. ct dynamic analysis of multiple traumatic pulmonary pseudo-cysts [ j]. computerized tomography theory and applications. 2013;1:023. 16. ulutas h, celik m, ozgel m, soysal o, kuzucu a. pulmonary pseudocyst secondary to blunt or penetrating chest trauma: clinical course and diagnostic issues. european journal of trauma and emergency surgery. 2015;41(2):181-8. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion conclusion: appendix references archives of academic emergency medicine. 2019; 7 (1): e69 ca s e re p o rt inhalational toxicity of aluminum phosphide as an ongoing concern; a report of two cases azam shafahi1, babak mostafazadeh2,3, bita dadpour1∗ 1. medical toxicology research center, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 2. toxicological research center, shahid beheshti university of medical sciences, tehran, iran. 3. department of forensic medicine and toxicology, shahid beheshti university of medical sciences, tehran, iran. received: august 2019; accepted: october 2019; published online: 17 november 2019 abstract: acute aluminium phosphide (alp) poisoning is an extremely lethal poisoning. ingestion is usually suicidal in intent, uncommonly accidental and rarely homicidal. unfortunately, the absence of a specific antidote results in very high mortality and the key to successful treatment is in rapid decontamination and institution of resuscitative measures. phosphine gas is highly toxic, and fatality is expected even several hours after continuous exposure. however, intensive supportive treatments may be lifesaving in some cases. here, two cases of accidental inhalation intoxication with alp are reported. one patient was discharged and another suffered cardiac arrest during treatment. keywords: aluminum phosphide; inhalation; inhalation exposure; gas poisoning cite this article as: shafahi a, mostafazadeh b, dadpour b. inhalational toxicity of aluminum phosphide as an ongoing concern; a report of two cases. arch acad emerg med. 2019; 7 (1): e69. 1. introduction aluminium phosphide (alp) poisoning as a suicidal attempt or accidental poisoning has become notorious in iran over the past decades. phosphine gas is a colorless, flammable and highly toxic substance, which is released when phosphide comes in contact with water (moisture) or acid, with an odor of garlic or decaying fish (1-3). by inhibition of cytochrome oxidase c and inducing oxidative stress, phosphine causes severe mitochondrial dysfunction, tissue hypoxia, and finally multiple organ failure (2, 4). common clinical manifestations include gastrointestinal symptoms, progressive metabolic acidosis, refractory hypotension, and dysrhythmia (4). most reports of alp poisoning are following ingestion of alp. unfortunately, phosphine gas inhalation also may lead to life threatening toxicity, even in large areas (4-6). to date, no specific antidote has been defined for this rapidly fatal poisoning and supportive measures are mainly recommended. immediate diagnosis in addition to continued in∗corresponding author: bita dadpour; department of clinical toxicology, imam reza hospital, mashhad, iran. tel: +989155149842, e-mail: dadpourb@mums.ac.ir tensive monitoring and supportive measures may be lifesaving. we aimed at reporting this incident from a public health emergency viewpoint as this type of (alp) poisoning may reoccur (although is relatively uncommon), at least in countries where alp is still used by general population. 2. cases presentation: a 60-year-old woman (case one), with her 29-year-old daughter (case two) were referred to a regional hospital and then transferred to clinical toxicology department of imam reza hospital, mashhad, iran, with upper abdominal discomfort, nausea, and with primary suspicion to food poisoning. 2.1. case one case one suffered from shortness of breath, weakness, dizziness, restlessness, and nausea on admission. vital signs at arrival included: sbp / dbp = 100/40 mmhg, rr = 20 / minute, o2 saturation= 93% on room air, and pr = 90 / minute. the patient had no fever and was alert and able to answer questions. there was no history of any drug addiction. she had a history of hypertension and diabetes. qtc prolongation was the most important finding of her electrocardiogram (ecg). hydration, oxygen therapy, cardiac monitoring and other supportive measures were performed. red blood cells and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. shafahi et al. 2 table 1: laboratory findings of case one laboratory parameters first day second day blood sugar (mg/dl) 251 241 creatinine (mg/dl) 1.1 1.2 urea (mg/dl) 31 43 sodium (mg/dl) 140 141 potassium (mg/dl) 3.2 3.2 calcium, total (mg/dl) 8.9 alanine aminotransferase (alt) (units/l) 46 37 aspartate aminotransferase(ast) (units/l) 89 61 alkaline phosphatase(alp) (units/l) 239 168 creatine phosphokinase (units/l) 124 145 cardiac troponin 89.30 magnesium (mg/dl) 2.4 serum cholinesterase 7356 rbc cholinesterase 5.2 complete blood count red blood cell ×106 4.56 4.20 hemoglobin 15.1 14.1 mean corpuscular volume(mcv ) 98.0 91.2 mean corpuscular hemoglobin(mch) 33.1 33.6 mean corpuscular hemoglobin concentration (mchc) 33.8 36.8 white blood cell ×3 7.4 6.0 neutrophil (%) 87.4 60.6 lymphocyte (%) 9.1 33.0 platelets ×103 183 185 table 2: venous blood gas analysis of the first patient on admission and 2, 5, and 8 hours after presenting to emergency department parameters on admission 2 hours 5 hours 8 hours ph 7.31 7.37 7.41 7.41 pco2 18.2 23 25.6 36.9 hco3 9.2 13.1 16 23.5 base excess -14.4 -0.1 serum cholinesterase levels were in normal range and serum test for the presence of acetaminophen, ethanol, methanol, and other toxic substance were negative. mild metabolic acidosis was evident in the first venous blood gas (vbg). results of other laboratory tests are shown in table 1. cardiology consult and echocardiography were performed and left ventricle ejection fraction (lvef) was 35%. with suspicion to alp poisoning, based on clinical and paraclinical findings, magnesium sulfate, bicarbonate, n-acetyl cysteine (nac) were initiated. nac was discontinued because of symptoms of hypersensitivity reactions. insulin was prescribed based on the routine protocol because of high blood sugar. ecg was repeated and prothrombin time was also reported high, which became normal in recheck. vbg was repeated several times and improved with supportive acidosis treatment. 2.2. case two vital signs of daughter on arrival included: systolic blood pressure (sbp)/ diastolic blood pressure (dbp) = 120/80 mmhg, respiratory rate (r.r) = 12 / minute, pulse rate (p.r) = 65 / minute. the patient had a seizure attack on admission and after a short time had a cardiac arrest. she was immediately intubated and cardiopulmonary resuscitation (cpr) was performed. unfortunately, resuscitation efforts were unsuccessful and she died after an hour. the course of events was so rapid that there was no time for any laboratory test. 2.3. cause of poisoning after taking a more accurate history it was revealed that the patient’s neighbor had sprayed a pesticide in his home two days earlier and had left the house. following investigations, it was determined that the mentioned poison was rice tablet (aluminum phosphide) which was obtained from an illegal center and was placed in the neighboring house in large numbers. the mother and daughter had been inhaling the poison odor for the past two days and had been at home all the time until they had progressive symptoms leading them to refer to hospital. history, clinical signs, and results of laboratory tests were in concordance with inhalation poisoning this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e69 with aluminum phosphide. on the fourth day of hospitalization after partial recovery, case one was discharged with personal consent against medical advice. 3. discussion cardiac arrest due to cardiac toxicity of alp inhalation led to death of case two in this report. phosphine gas toxicity following unintentional inhalation is not a common report in medical literature, although suicidal ingestion of aluminum phosphide tablets has been reported frequently in our country (2, 7, 8). the national institute for occupational safety and health (niosh) has established a limit for occupational exposure to phosphine gas at 0.3 ppm and has deemed it "immediately dangerous to life or health" at 50 ppm or more."(9). a study on different animals regarding degree of lethal exposure it has been reported that 200 ppm-hours leads to roughly 50% mortality (10). however, another study on male rats reported 11 ppm for 4 hours resulting in 50% lethality (9). phosphine gas concentration in this family’s home was certainly sufficient for major toxicity following several hours of exposure. an accurate estimation of fatality rates of phosphine gas inhalation is not possible. however, it is documented that phosphine is placed in the highest category of toxicity based on the environmental protection agency (epa) (9, 11, 12). in the current report, after 48 hours of inhalational exposure, death occurred. unfortunately, since there is no accepted definitive treatment for this lethal poisoning, supportive measures are the only treatment option at present. several maneuvers are suggested for possibly improving the outcome, including administration of n-acetylcysteine, magnesium sulfate, pralidoxime, and hyperinsulinemia uglycemia (13). although none of them are sufficiently evidence advocated at the present time (6). however, intensive supportive treatments may be lifesaving in some cases, like in the current report. 4. conclusion: phosphine gas is highly toxic, and fatality is expected even several hours after continuous exposure. a high level of vigilance and a more restrictive policy is needed for keeping the general population from having access to these pesticides and consequently preventing the high rate of mortality following this preventable poisoning in our community. 5. appendix 5.1. acknowledgements the authors express their appreciation to department of clinical toxicology, imam reza hospital, mashhad university of medical sciences, mashhad, iran. 5.2. authors contribution all authors devised the work, the main conceptual ideas, proof outline and interpretation of the data. also, all authors discussed the cases and commented on the manuscript. authors orcids azam shafahi: 0000-0002-1253-6262 babak mostafazadeh: 0000-0003-4872-9610 bita dadpour: 0000-0001-6004-0344 5.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present work. 5.4. funding all the expenses of this research were paid by the researchers. 5.5. ethical consideration all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. references 1. singh i, gupta k, agarwal s, bansal mk, samad a, kalra p. clinical efficacy of oral gabapentin versus clonidine for preemptive analgesia in knee arthroplasty under epidural anesthesia with 0.75% ropivacaine–a comparative study. indian journal of pain. 2019;33(1):15. 2. mehrpour o, amouzeshi a, dadpour b, oghabian z, zamani n, amini s, et al. successful treatment of cardiogenic shock with an intraaortic balloon pump following aluminium phosphide poisoning. archives of industrial hygiene and toxicology. 2014;65(1):121-7. 3. soltaninejad k, nelson ls, bahreini sa, shadnia s. fatal aluminum phosphide poisoning in tehran-iran from 2007 to 2010. indian journal of medical sciences. 2012;66(3-4):66-70. 4. mehrpour o, jafarzadeh m, abdollahi m. a systematic review of aluminium phosphide poisoning. archives of industrial hygiene and toxicology. 2012;63(1):61-73. 5. nosrati a, karami m, esmaeilnia m. aluminum phosphide poisoning: a case series in north iran. asia pacific journal of medical toxicology. 2013;2(3):111-3. 6. dadpour b, mokhtarpour m, abdollahi m, afshari r. an outbreak of aluminium phosphide poisoning in mashhad, iran. arhiv za higijenu rada i toksikologiju. 2016;67(1):65-6. 7. bagheri-moghaddam a, abbaspour h, tajoddini s, mohammadzadeh v, moinipour a, dadpour b. using intrathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. shafahi et al. 4 aortic balloon pump for management of cardiogenic shock following aluminum phosphide poisoning; report of 3 cases. emergency. 2018;6(1). 8. dadpour b, mehrpour o, oghabian z, dabbagh kakhki vr. the feasibility of evidence-based decision making in a toxicology emergency case. future of medical education journal. 2013;3(2):36-7. 9. lemoine tj, schoolman k, jackman g, vernon dd. unintentional fatal phosphine gas poisoning of a family. pediatric emergency care. 2011;27(9):869-71. 10. pepelko b, seckar j, harp pr, kim jh, gray d, anderson el. worker exposure standard for phosphine gas. risk analysis: an international journal. 2004;24(5):1201-13. 11. proudfoot at. aluminium and zinc phosphide poisoning. clinical toxicology. 2009;47(2):89-100. 12. sudakin d. occupational exposure to aluminium phosphide and phosphine gas? a suspected case report and review of the literature. human & experimental toxicology. 2005;24(1):27-33. 13. hashemi-domeneh b, zamani n, hassanianmoghaddam h, rahimi m, shadnia s, erfantalab p, et al. a review of aluminium phosphide poisoning and a flowchart to treat it. archives of industrial hygiene and toxicology. 2016;67(3):183-93. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction cases presentation: discussion conclusion: appendix references archives of academic emergency medicine. 2020; 8(1): e78 or i g i n a l re s e a rc h traumastem powder in treatment of non-traumatic anterior epistaxis in emergency department; a randomized clinical trial mahboob pouraghaei1, sina shafiee1, fahimeh mesrian1, haniyeh ebrahimi bakhtavar1, farzad rahmani1∗ 1. emergency medicine research team, tabriz university of medical sciences, tabriz, east azerbaijan, iran. received: august 2020; accepted: september 2020; published online: 4 october 2020 abstract: introduction: various studies are being conducted because of the value of finding an appropriate medication to control bleeding in patients with epistaxis faster and more conveniently. this study aimed to compare the effect of traumastem powder with routine tampons in treatment of non-traumatic epistaxis. methods: this randomized clinical trial enrolled patients with epistaxis presenting to the emergency departments of two hospitals affiliated to tabriz university of medical sciences. patients were divided into two groups using randomization software (intervention group: 107 patients, control group: 96 patients). primary outcome variables included bleeding control time and patient satisfaction. secondary outcome variable was recurrence of bleeding within the first 24 hours after treatment. visual assessment scoring system was used to assess patient satisfaction. results: epistaxis was controlled in less than 5 minutes in 85 (79.4%) patients in the intervention group and 85 (88.5%) patients in the control group (p=0.058). patient satisfaction in the intervention group was higher than that of the control group (p<0.05). in the intervention group, 10 patients experienced recurrence of epistaxis within 24 hours of treatment, while 9 patients in the control group experienced recurrence (p= 0.591). conclusion: based on the findings, bleeding control time was similar in the two groups, but patient satisfaction was higher in traumastem group. it is concluded that traumastem can conveniently control anterior epistaxis, but it is not successful in cases with severe bleeding. keywords: epistaxis; emergency service, hospital; treatment outcome; patient satisfaction cite this article as: pouraghaei m, shafiee s, mesrian f, ebrahimi bakhtavar h, rahmani f. traumastem powder in treatment of nontraumatic anterior epistaxis in emergency department; a randomized clinical trial. arch acad emerg med. 2020; 8(1): e78. 1. introduction epistaxis is a common medical problem, especially in older adults. the highest prevalence occurs in hospitalized patients under 10 and over 40 years of age (1, 2) . most of the epistaxis cases are idiopathic, and no primary risk factor is observed in 80%-90% of cases. the known causes of epistaxis include trauma (most common), nasal neoplasms, iatrogenic causes, and systemic causes (such as blood clotting, high blood pressure, inflammatory conditions, infectious diseases), medications (such as anticoagulants, antiplatelet, nasal sprays), and congenital anomalies of the nasal septum (1). ∗corresponding author: farzad rahmani; emergency department, tabriz university of medical sciences, golgasht street, azadi avenue, tabriz, iran. postal code: 5165665931, tel: 00984133352078, fax: 00984133352078, email: rahmanif@tbzmed.ac.ir various hemostatic dressings are used both in prehospital and hospital settings to control bleeding (5). furthermore, advanced procedures such as nasal endoscopy are successfully used to control epistaxis (6). zahed r. concluded that efficacy of topical use of tranexamic acid was higher than routine nasal tampon (7). ala a. reported no difference between celoxâl’ and routine tampon in bleeding control of idiopathic anterior epistaxis (8). traumastem powder is an absorbable sterile powder, made of calcium hydrogen salt of oxidized cellulose, which is mostly used in outpatient settings and surgical fields to stop capillary and venous bleeding. it is even suitable for stopping small superficial bleeding from lacerations. some of the outstanding features of this product include: it significantly increases the speed of clinical healing, has antibacterial effects, is completely absorbable, does not need to be removed from the wound, is non-irritating and hypoallergenic, does not cause any immunological processes, produces complete this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 2 homeostasis within 2 minutes, significantly reduces patient treatment costs, and has no side effects reported so far (3, 4). traumastem powder is a new treatment method, but no research has so far been conducted to compare its therapeutic effects with other topical medications available for the treatment of epistaxis. the aim of this study was to compare this treatment with routine nasal packing (shrinkage + tampon) in the treatment of epistaxis in patients presenting to the emergency department. 2. methods 2.1. study design and setting this randomized clinical trial was conducted on patients with epistaxis presenting to the emergency departments of imam reza and sina teaching hospitals affiliated to tabriz university of medical sciences, during dec 2018-jan 2020. this study was approved by the ethics committee of tabriz university of medical sciences (ir.tbzmed.rec.1397.480 on 10.05.2018). this study also was registered in iranian registry of clinical trials (irct20130224012592n6) on 08.10.2018. 2.2. participants inclusion criteria were: patients aged 18 to 65 years who presented to the emergency departments of the mentioned hospitals with anterior epistaxis. patients with coronary heart disease (inr>1.5), patients with multiple trauma, nasal trauma, arterial hemorrhage, shock, and patients who did not wish to participate in the study were excluded. 2.3. intervention to randomize samples, we used random allocation software to allocate the patients into two groups of traumastem and routine nasal packing. intention to treat was our analysis strategy. figure 1 shows the flowchart of the study. after obtaining informed consent, patients’ demographic information was recorded and initial measures were taken for the patient. at the same time, a blood sample was obtained to assess coagulation disorders (cbc-pt-ptt-inr). the traumastem group received a puff of traumastem (powder, 2 grams, bioster, a.s company, veverska bityska, czech republic) on the bleeding site and then the patient was asked to press their nostrils. the tampon group underwent the conventional method to control bleeding. first, three band cottons soaked in 2% lidocaine with epinephrine(1:10000) were used to shrink the nostrils, then a band mesh stained with 3% tetracycline ointment was used for anterior nasal packing (9). if bleeding control failed in the traumastem group, they received routine anterior nasal packing. 2.4. measurements of outcomes primary variables included bleeding control time and patient satisfaction. the secondary outcome variable was no recurrence of bleeding in the first 24 hours after treatment. both groups of patients were assessed for bleeding control at 5minute intervals, and bleeding control time was recorded. patient satisfaction was assessed using visual analog scale (vas) in which score 1 meant dissatisfaction and score 10 presented the greatest satisfaction. patient satisfaction was assessed on discharge from ed. the length of stay (los) of patients in the ed was collected. recurrence of bleeding was assessed by calling the patients 24 hours after the treatment. 2.5. statistical analysis to calculate the sample size of the study, the success rate of anterior nasal tampon in anterior epistaxis control within 10 minutes was considered as 31%, based on zahed’s study(7). probability of controlling bleeding under 10 minutes using a celox tampon cell for patients was considered 55% (∆ = 25%). by considering the power of 80% for the two-tailed test and using g power software (version 3.1.9.4., franz faul, universitat kiel, germany), the number of samples required for each group was calculated to be 93. data were analyzed using spss software (version 22.0, chicago, usa). descriptive statistics including quantity and percentage were used for qualitative variables, and mean and standard deviation were used for quantitative variables. the normal distribution of quantitative variables was analyzed using kolmogorov-smirnov test. the p value of this test was <0.05. thus, we used mann-whitney u test to analyze the quantitative variables. chi-square test was used to analyze qualitative variables. linear regression was used to analyze the relationship between quantitative variables. a p-value less than 0.05 was considered significant. 3. results in this study, 203 patients (107 patients in the traumastem group, 96 patients in the tampon group) were included. mean ± sd of patients’ age was 51.90±16.48 years (56.2% male). table 1 shows the comparison of demographics, vital signs, and laboratory variables of patients between the two groups. table 2 demonstrates the comparison of the data related to bleeding control and patient satisfaction in the two groups. as shown in table 2, there is no significant statistical difference between the two groups regarding bleeding control time (p value=0.764), but patient satisfaction was higher in traumastem group, and recurrence of bleeding within 24 hours of treatment was not significantly different between the 2 groups (p= 0.591). to evaluate the relationship between patient satisfaction this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e78 table 1: comparison of demographic data, vital signs, and laboratory variables of patients between the two groups variables traumastem n = 107 tampon n = 96 p age (years) 60.00 (45.00-62.00) 54.5 (36.00-62.75) 0.076* gender male 63 (58.9%) 51 (53.1%) 0.247& female 44 (41.1%) 45 (46.9%) epistaxis history yes 32 33 0.298& no 75 63 vital signs map# (mmhg) 90 (87-100) 90 (90-100) 0.301∗ heart rate (/minute) 81 (72-93) 85 (75-90) 0.376* laboratory data platelet (/mm3 ) 230000 (190000-270000) 215000 (167250-298000) 0.494∗ pt# (second) 13 (13-13) 13 (13-13) 0.410∗ ptt# (second) 33 (32-35) 33 (32-35) 0.287∗ inr# 1 (1-1.10) 1 (1-1.10) 0.452* # map: mean arterial pressure; pt: prothrombin time; ptt: partial thromboplastin time; inr: international normalized ratio. data are presented as median (iqr 25-75%) or number (%). ∗: mann u whitney; & : chi square. table 2: comparison of data on bleeding control and patients’ satisfaction in the two groups variables traumastem n= 107 tampon n=96 p bleeding control time (minute) median (iqr 25-75%) 4.00 (3.00-5.00) 4.00 (3.00-4.00) 0.764* satisfaction level median (iqr 25-75%) 8.00(8.00-9.00) 6.00 (6.00-7.00) <0.001* length of stay in ed (minute) median (iqr 25-75%) 85.00 (45.00-110.00) 60.00 (45.00-88.00) 0.095* control of bleeding≤5minutes yes 85 (86.7) 85 (88.5) 0.058& no 22 (20.6) 11 (11.5) re-bleeding after 24 hours yes 10 (9.3) 9 (9.4) 0.591& no 97 (90.7) 87 (90.6) ed: emergency department; ∗: mann u whitney; & : chi square. level and time of bleeding control, we used linear regression (figure 2). based on the results of this test, there was a significant statistical correlation between these two variables, as satisfaction level was higher when time of bleeding control was shorter (r=0.356, p value<0.001). in 5 cases in the early moments of traumastem use, this agent led to sneezing, so we tried to use a routine nasal tampon to stop bleeding, and these patients were excluded from the study. to calculate the absolute risk reduction (arr), relative risk (rr), and the number need to harm (nnh) of the new treatment of epistaxis, we used the number of patients with successful bleeding control under 5 minutes in each group. the results showed that the arr, rr, and nnh were -0.09 (95% ci -0.19 0.074), 1.79 (95% ci 0.92 3.5) and 10.99 (95% ci -5.24 116.37), respectively. 4. discussion in this study, we evaluated the efficacy of traumastem powder for bleeding control in epistaxis. there was no significant statistical difference between the two groups regarding bleeding control time (p value: 0.764), but there was significant difference in patients’ satisfaction rate (p value<0.001). epistaxis, which is most often benign, is one of the common complaints in emergency departments (10). most of the epistaxis cases are treated with simple measures at home or out of the hospital, but some of them require hospital admission and professional medical treatments (11). many treatment modalities have been introduced to control bleeding in epistaxis (12). some of the anterior nasal bleeding treatments include direct nasal pressure, chemical cauterization, thrombogenic foams and gels, and anterior and posterior nasal packing (8, 9, 13, 14). different studies have also been conducted to evaluate new treatments and compare their effithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 4 figure 1: flowchart of the study. cacy and patient satisfaction (6-8). recently, oxidized cellulose-containing hemostatic powders have been introduced to control capillary, venous, and small arterial hemorrhages in inaccessible areas. different studies have evaluated the efficacy of these products (15-19). zou y. compared endoscopic surgery and nasal packing in posterior epistaxis, and reported no significant differences between the two methods in the basic features, but the degree of adhesion of the nasal cavity was significantly lower in the surgery group compared to the nasal packing group (6). farnetti p. compared topical sclerotherapy using lauromacrogol with nasal packing in treatment of epistaxis, and reported the recurrence rate to be significantly higher in the nasal packing group compared to the other group (1). murray s. et al. concluded that floseal was a comfortable, effective, and cost-effective alternative in treatment of resistant epistaxis compared to the old packing method in patients with normal coagulation profile (2). zahed r. concluded that tranexamic acid had a better effect on epistaxis control compared to other methods (7). ala a. et al. reported no better results with celox© bands in terms of bleeding control time in comparison to routine tampon, but satisfaction level was higher in the celox© group (8). in this study, 107 patients were included in the traumastem group (intervention) and 96 patients were allocated to the tampon group (control). there were no significant statistical differences between the two groups regarding demographics, primary vital signs and laboratory data (p value>0.05). in the acute treatment of epistaxis and rebleeding rate within 24 hours of treatment, traumastem was not better than routine anterior nasal packing. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e78 figure 2: relationship between patient satisfaction level (vertical axis) and time of bleeding control (horizontal axis). 5. limitation the significant limitation of our study was in the blinding stage, considering the differences between the types of methods used, it was impossible to blind the patients or physicians to the methods. in some of the patients with severe bleeding, it took traumastem a long time to control bleeding, which negatively affected these patients’ satisfaction. in some patients, in the early moments of using the powder, it induced sneezing, which was a limitation for its use. 6. conclusion based on the findings, bleeding control time was similar in the two groups, but patient satisfaction was higher in the traumastem group. in addition, recurrence rate of bleeding within 24 hours of treatment was similar in both groups. we need further studies on the efficacy and applicability of (traumastem) in routine practice to assess the generalizability (external validity, applicability) of the results of the present study. 7. declarations 7.1. acknowledgements the authors are grateful to all of those who participated in the study. this article was written based on the dataset of sina shafiee md’s thesis entitled" comparison of traumastem powder with routine tampon in the treatment of nontraumatic epistaxis ", registered in tabriz university of medical sciences (no: 95/1-4/17, oct 13, 2016). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. pouraghaei et al. 6 7.2. author contribution all authors have read and approved the manuscript. ss, fm, and mp performed data collection, writing, critical revision and drafting of the manuscript. heb and fr undertook the major parts of the study design and performed the statistical analysis, and data interpretation. 7.3. funding/support this article was supported by emergency medicine research team, tabriz university of medical sciences, tabriz, iran. special thanks to research vice chancellor of tabriz university of medical sciences for materially and financially supporting our study. all the medications have been purchased using the budget provided by the university vice chancellor for research. 7.4. conflict of interest the authors have no conflicts of interest. references 1. farneti p, pasquini e, sciarretta v, macrãň g, gramellini g, pirodda a. comparison of local sclerotherapy with lauromacrogol versus nasal packing in the treatment of anterior epistaxis. clin exp otorhinolaryngol. 2016;9(2):131-5. 2. murray s, mendez a, hopkins a, el-hakim h, jeffery cc, cote dwj. management of persistent epistaxis using floseal hemostatic matrix vs. traditional nasal packing: a prospective randomized control trial. j otolaryngol head neck surg. 2018;47(1):3-. 3. http://www.traumastem.eu czech republic bioster a.s. 4. zboril p, vyslouzil k, klementa i, stary l, skalicky p, ruzicka v. ambulantni excize perianalnich duplikatur [ambulatory excision of perianal duplicatures]. rozhl chir. 2010;89(12):774-9. 5. granville-chapman j, jacobs n, midwinter mj. prehospital haemostatic dressings: a systematic review. injury. 2011;42(5):447-59. 6. zou y, deng yq, xiao cw, kong yg, xu y, tao zz, et al. comparison of outcomes between endoscopic surgery and conventional nasal packing for epistaxis in the posterior fornix of the inferior nasal meatus. pakistan journal of medical sciences. 2015;31(6):1361-5. 7. zahed r, moharamzadeh p, alizadeharasi s, ghasemi a, saeedi m. a new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. the american journal of emergency medicine. 2013;31(9):1389-92. 8. ala a, rahmani f, shirzadegan s, ebrahimi bakhtavar h, mehdizadeh esfanjani r. non -traumatic epistaxis management using celox®dressing: a randomized clinical trial. iran red crescent med j. 2018;20(4):e58374. 9. mcginnis hd. nose and sinuses. in: tintinalli je, editor. tintinalli’s emergency medicine. 9 ed. china: mc graw hill; 2020. p. 1572-9. 10. sarhan na, algamal am. relationship between epistaxis and hypertension: a cause and effect or coincidence? j saudi heart assoc. 2015;27(2):79-84. 11. alyahya k, alsaad s, alsuliman s, alsuliman n. awareness about first aid management of epistaxis among medical students in kingdom of saudi arabia. j family med prim care. 2019;8(3):914-8. 12. newton e, lasso a, petrcich w, kilty sj. an outcomes analysis of anterior epistaxis management in the emergency department. j otolaryngol head neck surg. 2016;45:24-. 13. bachelet jt, bourlet j, gleizal a. hemostatic absorbable gel matrix for severe post-traumatic epistaxis. rev stomatol chir maxillofac chir orale. 2013;114:310-4. 14. toner jg, walby ap. comparison of electro and chemical cautery in the treatment of anterior epistaxis. j laryngol otol. 1990;104:617-. 15. hutchinson rw, werrlein s, johns db, zhang g, clymer jw, kocharian r. an in vivo comparison of hemostatic gelatin matrix products in a porcine spleen biopsy-punch model. surgical technology international. 2015;27:53-7. 16. macdonald mh, wang ay, clymer jw, hutchinson rw, kocharian r. an in vivo comparison of the efficacy of hemostatic powders, using two porcine bleeding models. medical devices (auckland, nz). 2017;10:273-9. 17. martyn d, meckley lm, miyasato g, lim s, riebman jb, kocharian r, et al. variation in hospital resource use and cost among surgical procedures using topical absorbable hemostats. clinicoecon outcomes res. 2015;7:567-74. 18. rembe j-d, bohm jk, fromm-dornieden c, schafer n, maegele m, frohlich m, et al. comparison of hemostatic dressings for superficial wounds using a new spectrophotometric coagulation assay. j transl med. 2015;13:375-. 19. wright jd, ananth cv, lewin sn, burke wm, siddiq z, neugut ai, et al. patterns of use of hemostatic agents in patients undergoing major surgery. j surg res. 2014;186(1):458-66. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e53 or i g i n a l re s e a rc h point of care ultrasound in detection of brain hemorrhage and skull fracture following pediatric head trauma; a diagnostic accuracy study maryam masaeli1, mojtaba chahardoli2, sepehr azizi1,2 ∗, babak shekarchi3, foroogh sabzghabaei4, nima shekar riz fomani2, mahdi azarmnia1, mahdis abedi2 1. emergency department, besat hospital, school of medicine, aja university of medical sciences, tehran, iran. 2. emergency department, firouzgar hospital, school of medicine, iran university of medical sciences, tehran, iran. 3. department of radiology, school of medicine, aja university of medical sciences, tehran, iran. 4. department of medicine, firouzgar hospital, school of medicine, iran university of medical sciences, tehran, iran. received: june 2019; accepted: august 2019; published online: 24 september 2019 abstract: introduction: head trauma is a common reason for emergency department visits worldwide; many of which involve young children. we sought to determine if head ultrasound (us), as a portable, fast and safe modality, can guide diagnosis and treatment of children in emergency settings. methods: in this cross-sectional study, brain computed tomography (ct) scan and emergency head us were performed on head trauma children who were referred to the emergency departments of firouzgar and besat hospitals, tehran, iran, from september 2018 to may 2019. the findings of the two modalities were separately evaluated, and used to estimate the diagnostic accuracy of us. results: 538 patients with the mean age of 5.6 ± 4.9 (0-18) years were studied (54.8% male). sensitivity and specificity of bedside us in detection of hemorrhage were 85.71% (42.13%-99.64%) and 97.99% (94.23%-99.58%) for children below the age of 2. these measures were 80.00% (51.91%-95.67%) and 97.97% (94.88%-99.44%), respectively, for those between 2 and 6 years old and 46.67% (21.27%-73.41%) and 92.90% (87.66%-96.40%), respectively, for those above the age of 6. sensitivity and specificity were 92.31% (84.01%97.12%) and 95.87% (93.62%-97.50%), respectively, in diagnosing skull fractures. cohen’s kappa coefficient varied greatly for different findings, ranging from 0.363 to 0.825, indicating different agreement rates for each. conclusion: based on our findings, emergency us can play a greater role in the initial management of head trauma children, especially as a triage test. keywords: emergency medicine; pediatrics; craniocerebral trauma; skull fractures; intracranial hemorrhages; ultrasonography cite this article as: masaeli m, chahardoli m, azizi s, shekarchi b, sabzghabaei f, shekar riz fomani n, azarmnia m, abedi m. point of care ultrasound in detection of brain hemorrhage and skull fracture following pediatric head trauma; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e53. 1. introduction head trauma is a common reason for emergency department visits worldwide; many of which involve young children. in the civilian population, almost 75% of head trauma is due to falls and motor vehicle accidents (1). blast-induced traumatic brain injury (tbi) is also considered a major cause of ∗corresponding author: sepehr azizi; emergency department, besat hospital, school of medicine, aja university of medical sciences, tehran, iran. email: sepehr.azizi70@gmail.com, tel: 00989128261260 neuropsychological morbidity during and after wars (2, 3). early presentation of mild tbi is rather nonspecific and may include persistent headaches, vertigo, memory loss and poor concentration (4). the situation needs to be tackled immediately, since any delay in diagnosis and treatment of intracranial injuries can result in rapid deterioration, death, or permanent neurological sequel. the standard imaging test for head trauma patients is non-contrasted computed tomography (ct) scan of brain (5). it is estimated that about one million children undergo unnecessary ct in the usa each year (6). no surprise that various clinical decision rules have been proposed for decreasing its excessive use (7). a number of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masaeli et al. 2 reasons limit ct application: it is expensive, it is not available in smaller centers, and it employs ionizing radiation; which is especially worrying in children. furthermore, sedation is very often required for performing the procedure in young children, which poses an extra risk (8). point-of-care ultrasonography (us) is increasingly used as a diagnostic tool in emergency departments (9). us is fast, safe, portable, cost-effective and well tolerated even by children (10). but the critical question remains open, as to how promising it is for clinical decision making concerning head trauma. some evidence suggests that us is accurate for pediatric skull fractures (11, 12). interestingly enough, there is 20 times more risk of suffering an intracranial injury, for those who are found to have a skull fracture (13). less research has been conducted on detection of traumatic brain hemorrhages via us. to our knowledge, there are no studies discussing us diagnosis of cranial hemorrhages except for newborns and infants. although there is still doubt about suitability of us for these areas due to the known attenuating effect of bone on ultrasonic waves (14, 15), the rewards of developing us to a triage tool, particularly for disasters and tactical conditions, are huge. we sought to determine if head us performed by emergency physicians, can guide diagnosis and treatment of children in emergency settings. based on the above mentioned reasons, the present study aimed to evaluate the accuracy of point of care us in detection of brain hemorrhage and skull fractures following pediatric head trauma. 2. methods 2.1. study design and setting in this prospective cross-sectional study, brain ct-scan and head us were performed separately for head trauma children who were referred to emergency departments of firouzgar and besat hospitals, tehran, iran, from september 2018 to may 2019 (a 7-month period). the findings of the two modalities along with patients’ demographic data (age, sex), were then collected using a checklist by a trained emergency medicine resident and were used to estimate the diagnostic accuracy of us in detection of brain hemorrhage and skull fractures, by relying on ct-scan as the reference test. the study protocol was reviewed and approved by ethics committee of aja university of medical sciences (ethics code: ir.ajaums.rec.1397.118) and researchers adhered to the principles of helsinki declaration. there was no interference with routine management of patients, since ultrasounds were performed while patients were awaiting transfer to the radiology department. before enrollment, informed consent was obtained from the patients or their surrogate decision makers. 2.2. participants patients younger than 18 years presenting within 24 hours of head trauma were studied. sources of subject recruitment were emergency departments of firouzgar and besat hospitals, which are among tertiary referral hospitals, in tehran, iran. the two centers had common head trauma management protocols. to identify children who were candidates of head ct-scan, the pecarn prediction rule was used (6). pecarn recommends obtaining head ct imaging and observation in the presence of altered mental status, palpable skull fracture, scalp hematoma, loss of consciousness, vomiting, severe headache, not acting normally according to parents, and severe mechanism of injury (6). these patients were enrolled for also having a bedside us evaluation using non-probability sampling. uncooperative patients, patients with gcs≤13 and those with acute hemodynamic instability were excluded. patients who met the aforementioned criteria were selected consecutively. 2.3. imaging details point of care us was performed by attending emergency physicians and trained third year emergency medicine residents, and head ct-scans were interpreted by radiology department. third year emergency medicine residents were first trained in an emergency us workshop, including a theoretical session as well as hands-on practice, under supervision. the training course met the requirements of the current guideline by the american college of emergency physicians (9). for detection of brain hemorrhages, the children were assigned to three age groups; patients under 2 years old, 2 to 6 years old, and 6 to 18 years old. as the bones continue to ossify, high-impedance difference between bone and soft tissue prohibits visualization of the underlying structures. accordingly, the 2 years old point was chosen due to the fact that the closure of anterior fontanel is expected to occur by maximum of 18-24 month (16). the ossification further continues so that the spheno-ethmoidal synchondrosis is lost at 6-7 year (17). this produces another plausible cut-off since the cranium is 90% of the adult size at this time (18). us was performed using 2-5 mhz transducer, phased array, sonosite m-turbo machines. the scalp was first examined for soft-tissue swelling, bruising and other local signs. cortical irregularities were noted for diagnosing linear and depressed fractures. for detecting blood, echogenicity patterns were probed. subdural and epidural hematomas commonly present as hypoechoic fluid collections surrounding the brain parenchyma (19). examinations began using bilateral trans-temporal approach. in infants, anterior and posterior fontanels were also used as fine acoustic windows to the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e53 cranial vault. the occipital window was reserved for patients with ruled out cervical spine injury. then, patients were transferred to obtain their ct scan. on ct, acute extra-axial hemorrhages are usually hyper-attenuating. hyperacute unclotted blood may be close to water attenuation, while mixed high and low attenuation pattern suggests active bleeding. skull fractures are also seen in 85% to 95% of cases with epidural hematoma (20). the findings of brain ct scan were interpreted by radiologists and the research team later reviewed ct scan reports. at the time of performing the procedures, the us and radiology teams were blind to each other’s findings. individual discussion with surrogate decision makers was used to allay anxiety when recruiting patients. investigators made all examinations on a single occasion, and no further follow-up was scheduled after the emergency department visit. 2.4. data gathering patients’ baseline characteristics as well as head us and brain ct scan findings were collected for patients using a predesigned checklist by a trained emergency medicine resident. 2.5. statistical analysis the minimum required sample size considering 17% prevalence of abnormal brain ct scan findings in suspected mild tbi patients (21), 94% estimated sensitivity of us in pilot, 95% confidence interval (α=0.05), and estimation error of 5% (d= 0.05), was calculated as 510 subjects. we finally enrolled 538 cases to avoid errors due to unexpected dropouts. data was transferred to statistical package for social sciences (spss) software version 22. mean and standard deviation were used to report quantitative data. qualitative data were presented as frequency and percentage. cohen’s kappa coefficient was calculated, as a measure of inter-rater agreement between brain ct scan and head us reports. sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of us in detection of intracranial hemorrhage and skull fracture, were calculated using medcalc’s statistical software, considering ct reports as the reference test. in all cases, p<0.05 was considered significant. since there were very few missing values, we used casewise deletion to address missing data. 3. results 3.1. baseline characteristics of studied cases a total of 538 consecutive head trauma children with the mean age of 5.6 ± 4.9 years (range: 0-18) were studied (54.8% male). traumas were most commonly due to falls (43.8%). 49 patients were hypotensive (9.1%). a period of loss of consciousness was reported in 60 cases. (11.1%) table 1 depicts table 1: baseline characteristics of studied patients variable number (%) gender male 295 (54.8) female 243 (45.1) age (year) <2 156 (28.9) 2-6 212 (39.4) 6-18 170 (31.5) trauma mechanism falls 236 (43.8) motor vehicle accidents 82 (15.2) other 220 (40.8) hypotension no 489 (90.8) yes 49 (9.1) loss of consciousness (gcs < 15) no 478 (88.8) yes 60 (11.1) headache* no 312 (57.9) yes 226 (42.0) vomiting no 492 (91.4) yes 46 (8.5) seizure no 530 (98.5) yes 8 (1.48) *for ≥2 years’ cases. hypotension: systolic blood pressure < 90 mmhg. gcs: glasgow coma scale. baseline characteristics of the patients. 3.2. screening performance characteristics the agreement rate between us and brain ct scan in detection of brain hemorrhage and skull fractures is presented in table 2. the lowest and highest agreement between us and brain ct scan reports were regarding detection of hemorrhage in 6 to 18 year-old patients (kappa: 0.363) and skull fracture (kappa: 0.825), respectively. screening performance characteristics of head us in detection of brain hemorrhage and skull fractures are summarized in table 3. sensitivity and specificity of bedside us in detection of hemorrhage below the age of 2 were 85.71% (95%ci: 42.13%-99.64%), 97.99% (95%ci: 94.23%-99.58%), respectively. in children between 2 and 6 years old the results were 80.00% (95%ci: 51.9%-95.67%) and 97.97% (95%ci: 94.88%-99.44%), respectively. above the age of 6 the sensitivity and specificity were 46.67% (95%ci: 21.27%-73.41%) and 92.90% (95%ci: 87.66%-96.40%), respectively. for diagnosing skull fractures, sensitivity and specificity of us were 92.31% (95%ci: 84.01%-97.12%) and 95.87% (95%ci: 93.62%97.50%), respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. masaeli et al. 4 table 2: agreement between head ultrasonography and brain computed tomography (ct) scan findings of studied patients variables true positive n (%) cohen’s kappa strength ultrasonography ct scan brain hemorrhage <2 years 6 (3.8) 7 (4.4) 0.73 (0.49 0.98) good 2-6 years 12 (5.6) 15 (7.0) 0.75 (0.58 0.93) good 6-18 years 7 (4.1) 15 (8.8) 0.36 (0.13 0.58) fair fracture skull 72 (13.3) 78 (14.4) 0.82 (0.75 0.89) very good table 3: screening performance characteristics of ultrasonography in detection of brain hemorrhage and skull fracture following head trauma characteristics brain hemorrhage skull fracture <2 years 2-6 years 6-18 years true positive 6 12 7 72 false negative 1 3 8 6 false positive 3 4 11 19 true negative 146 193 144 441 sensitivity 85.7 (42.1-99.6) 80.0 (51.9-95.6) 46.6 (21.2-73.4) 92.3 (84.0-97.1) specificity 97.9 (94.2-99.5) 97.9 (94.8-99.4) 92.9 (87.6-96.4) 95.8 (93.6-97.5) ppv 66.6 (38.5-86.4) 75.0 (52.4-89.1) 38.8 (22.4-58.2) 79.1 (70.8-85.5) npv 99.3 (95.9-99.8) 98.4 (95.9-99.4) 94.7 (91.8-96.6) 98.6 (97.1-99.3) plr 42.5 (13.3-135.8) 39.4 (14.4-107.3) 6.5 (3.0-14.4) 22.3 (14.3-34.8) nlr 0.15 (0.020.90) 0.20 (0.07-0.56) 0.5 (0.3-0.9) 0.08 (0.04-0.17) all measures are presented with 95% confidence interval (ci). plr: positive likelihood ratio; nlr: negative likelihood ratio; ppv: positive predictive value; npv: negative predictive value. 4. discussion based on the findings, the strength of agreement between head us and brain ct scan in diagnosis of skull fractures, and hemorrhages in the age groups of under 2 years, 2 to 6 years and 6 to 18 years can be categorized as very good (k:0.82), good (k:0.73), good (k:0.75) and fair (k:0.36), respectively. a very good agreement (kappa: 0.825) between head us and brain ct scan regarding the absence or presence of skull fracture, is generally consistent with prior studies. for instance, parri et al. reported 100% sensitivity and 95% specificity of us in diagnosing skull fractures (11). point-of-care us of rabiner et al. on 69 patients under the age of 21, also reported 88% sensitivity and 97% specificity in detection of skull fracture (22). in another study, steiner and colleagues examined 210 children with head trauma. they recommended employing us as a screening test for skull fracture, so the patients with negative us and normal neurological status could only be observed (23). similarly, us had a higher negative predictive value than positive predictive value in our study. mccormick and colleagues assessed the accuracy of us performed by emergency physicians in diagnosis of traumatic intracranial hemorrhage (ich) in infants. in their study, physicians demonstrated a range of 50% to 100% sensitivity (kappa: 0.4) (24). our study may be the first to explore the feasibility of emergency us for diagnosing brain hemorrhages in children with head trauma. independent comprehensive reviews of evidence regarding pediatric emergency medicine point of care us in 2014 and 2016, did not report any evidence on this issue (25, 26). in our study, the strength of agreement between emergency us and ct scan was good for detection of bleeding up to 6 years of age (kappa: 0.737 and 0.756 for 0 to 2 years old and 2 to 6 years old, respectively). however, in older children a dramatic fall was obvious in agreement between us and ct scan (kappa: 0.363). 41.6% (n: 5) of us false negative cases were further diagnosed and localized by ct scan as small frontal bleedings. under the age of 2, 100% (n: 3) of us false positive cases were misdiagnosed as small temporal ich, which were further ruled out by brain ct scan. 5. limitation one of the limitations of the present study, is that we cannot know how introducing us in the management would affect patients’ outcome. developing head us into a reliable part of clinical decision making requires information on patients’ prognosis. our results may also need further confirmation for their generalizability. although we conducted a multicenter study, both institutions were tertiary large hospitals. therefore, we recommend that researchers conduct similar studies in primary and secondary care settings of smaller fathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e53 cilities. us results depend on the operators’ training, skill and experience, so accuracy may vary from operator to operator. we did not study inter-observer variability of us findings. it is indispensable that the scope of emergency us be clearly defined by further investigators, so that medical associations will be able to issue guidelines on appropriate method of application, evaluation and certification of us in pediatric head trauma. 6. conclusion based on the findings of the present study, there was a very good agreement between head us and brain ct scan findings regarding the absence or presence of skull fracture. the strength of agreement was slightly lower for detection of bleeding in children up to 6 years of age. this can make us a suitable option for initial assessment of head trauma in infants and young children. yet, significantly lower agreement in those above 6 years old demonstrates the necessity of not overgeneralizing the capabilities of us in older children. still, it may prove beneficial in disasters. 7. appendix 7.1. acknowledgements the authors greatly appreciate the cooperation of patients, residents and staff of emergency and radiology departments of aja and iran universities of medical sciences during the study period. 7.2. author contribution all authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. authors orcids maryam masaeli: 0000-0002-5023-5401 mojtaba chahardoli: 0000-0002-5438-2484 sepehr azizi: 0000-0002-2342-1110 babak shekarchi: 0000-0001-9741-9825 foroogh sabzghabaei: 0000-0002-6819-7079 nima shekar riz fomani: 0000-0003-3542-923x mahdi azarmnia: 0000-0001-7306-4396 mahdis abedi: 0000-0002-2804-3964 7.3. funding/support none. 7.4. conflict of interest the authors declare that there is no conflict of interest. references 1. faul m, wald mm, xu l, coronado vg. traumatic brain injury in the united states; emergency department visits, hospitalizations, and deaths, 2002-2006. 2010. 2. ling g, ecklund j, bandak f. brain injury from explosive blast: description and clinical management. handbook of clinical neurology. 127: elsevier; 2015. p. 173-80. 3. miller sc, whitehead cr, otte cn, wells ts, webb ts, gore rk, et al. risk for broad-spectrum neuropsychiatric disorders after mild traumatic brain injury in a cohort of us air force personnel. occup environ med. 2015;72(8):560-6. 4. norris jn, smith s, harris e, labrie dw, ahlers st. characterization of acute stress reaction following an ied blast-related mild traumatic brain injury. brain injury. 2015;29(7-8):898-904. 5. papa l, goldberg s. head 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15. aaslid r, markwalder t-m, nornes h. noninvasive transcranial doppler ultrasound recording of flow velocity in basal cerebral arteries. journal of neurosurgery. 1982;57(6):769-74. 16. boran p, oguz f, furman a, sakarya s. evaluation of fontanel size variation and closure time in children followed up from birth to 24 months. journal of neurosurgery: pediatrics. 2018;22(3):323-9. 17. hill ma. embryology musculoskeletal system skull development 2019, september 17 [cited 2019 08-jun-2019]. available from: https://embryology.med.unsw.edu.au/embryology/index. php/musculoskeletal_system_-_skull_development. 18. jha rt, magge sn, keating rf. diagnosis and surgical options for craniosynostosis. principles of neurological surgery: elsevier; 2018. p. 148-69. e7. 19. chamnanvanakij s, rollins n, perlman jm. subdural hematoma in term infants. pediatric neurology. 2002;26(4):301-4. 20. barr rm. craniofacial trauma. in: brant we, helms ca, editors. fundamentals of diagnostic radiology. 4th ed: lippincott williams & wilkins; 2012. p. 51. 21. papa l, goldbergwalls sa. head trauma. in: walls r, hockberger r, gausche-hill m, editors. rosen’s emergency medicine-concepts and clinical practice. 9th ed: elsevier health sciences; 2017. p. 301. 22. rabiner je, friedman lm, khine h, avner jr, tsung jw. accuracy of point-of-care ultrasound for diagnosis of skull fractures in children. pediatrics. 2013;131(6):e1757e64. 23. steiner s, riebel t, nazarenko o, bassir c, steger w, vogl t, et al. skull injury in childhood: comparison of ultrasonography with conventional x-rays and computerized tomography. rofo: fortschritte auf dem gebiete der rontgenstrahlen und der nuklearmedizin. 1996;165(4):353-8. 24. mccormick t, chilstrom m, childs j, mcgarry r, seif d, mailhot t, et al. point-of-care ultrasound for the detection of traumatic intracranial hemorrhage in infants: a pilot study. pediatric emergency care. 2017;33(1):18-20. 25. gallagher ra, levy ja. advances in point-of-care ultrasound in pediatric emergency medicine. current opinion in pediatrics. 2014;26(3):265-71. 26. marin jr, abo am, arroyo ac, doniger sj, fischer jw, rempell r, et al. pediatric emergency medicine point-ofcare ultrasound: summary of the evidence. critical ultrasound journal. 2016;8(1):16. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e45 or i g i n a l re s e a rc h value of ultrasonography in detection of diaphragmatic injuries following thoracoabdominal penetrating trauma; a diagnostic accuracy study ali sharifi1, amir kasraianfard1, abdolhamid chavoshi khamneh2, soheila kanani3, mohamedali aldarraji4, mohammad ali seif-rabiei5, amir derakhshanfar1∗ 1. department of general surgery, hamadan university of medical sciences, hamadan, iran. 2. department of general surgery, iran university of medical sciences, tehran, iran. 3. department of emergency medicine, hamadan university of medical sciences, hamadan, iran. 4. general physician, shahed medical faculty, tehran, iran. 5. department of social medicine, hamadan university of medical sciences, hamadan, iran. received: may 2019; accepted: july 2019; published online: 18 august 2019 abstract: introduction: diagnosis of diaphragmatic rupture following thoracoabdominal penetrating trauma is very challenging in asymptomatic patients with stable vital signs. this study aimed to evaluate the diagnostic accuracy of focused assessment with sonography for trauma (fast) in this regard. methods: this cross-sectional study was performed on patients referring to emergency department due to left thoracoabdominal stab wound during 2 years. all patients initially underwent ultrasonography and the screening performance characteristics of fast in detection of diaphragmatic injuries were calculated, considering the findings of diagnostic laparoscopy as the gold standard test. results: twenty-four patients with the mean age of 33 ± 10.64 years (16-61 years) were studied (100% male). the mean chest wall laceration size was 2.7 ± 2.7 cm (1-10 cm) and the most frequent location of wounds was posterior chest wall (42%) and in the 6th and 7th intercostal space (50%). diaphragmatic rupture was seen in 4 (16.7%) patients based on diagnostic laparoscopy. sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of fast in detection of diaphragmatic raptures were 50% (95% ci: 9.18 – 90.8), 100% (95% ci: 79.9 – 100.0), 100% (95% ci: 19.8 – 100.0), 9.1% (95% ci: 1.5 – 30.6), infinity, and 0.1 (95% ci: 0.02 – 0.37), respectively. the overall accuracy of fast in this regard was 75.0% (95% ci: 42.3 – 100.0). conclusion: in patients with penetrating trauma to the left thoracoabdominal region, fast cannot be the definitive alternative to diagnostic laparoscopy to detect diaphragm rupture. keywords: wounds, stab; diaphragm; wounds and injuries; focused assessment with sonography of trauma; laparoscopy cite this article as: sharifi a, kasraianfard a, chavoshi khamneh a, kanani s, aldarraji m, seif-rabiei m a, derakhshanfar a. value of ultrasonography in detection of diaphragmatic injuries following thoracoabdominal penetrating trauma; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e45. 1. introduction thoracoabdominal penetrating trauma is one of the common problems in surgical emergency centres. in patients with a penetrating trauma and unstable hemodynamic status, the primary and standard approach to diagnosis and ∗corresponding author: amir derakhshanfar; department of general surgery, faculty of medicine, hamadan university of medical sciences, shahid fahmide ave., hamadan, iran. tel: +98 81 38380452, fax: +98 81 38380208, e-mail: dramirderakhshanfar@gmail.com treatment is surgical intervention, which can be explorative laparotomy or thoracotomy based on clinical assessment (1). diagnosis of diaphragmatic rupture in patients with thoracoabdominal penetrating trauma is controversial in those who are hemodynamically stable and asymptomatic (2). in some clinical centres, those with penetrating lacerations of the thoracoabdominal area routinely undergo surgical explorations (3). using this method, all diaphragmatic ruptures are detected, but a large number of patients undergo negative laparotomy, which leads to complications such as postsurgical adhesion or surgery wound site infections. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sharifi et al. 2 in addition, this method is very time consuming and costly, especially in the crowded trauma centres with a large number of visitors. therefore, several diagnostic methods including chest radiography, computed tomography (ct) scan and diagnostic peritoneal lavage have been used to diagnose diaphragmatic rupture, but their diagnostic accuracies have been reported as very poor in various studies (4). focused assessment with sonography for trauma (fast) is a very suitable diagnostic method for patients with trauma, which is very easy to use and does not require general anaesthesia and is not likely to cause any harm to the patient (57). using ultrasound has a sensitivity of 94%, specificity of 98% and approximate accuracy of 95% for detecting intraabdominal bleeding and visceral injury (8). in this study, we aimed to determine the accuracy of fast in detecting diaphragmatic rupture in patients with stab wound of sharp objects in thoracoabdominal region and to compare the results with diagnostic laparoscopy. 2. methods 2.1. study design and setting this was a cross-sectional (diagnostic accuracy) study conducted on all patients who were referred to the emergency department of besat hospital, hamadan, iran, following thoracoabdominal penetrating trauma, from 2016 to 2018. the screening performance characteristics of fast sonography in detection of diaphragmatic injuries were calculated, considering the findings of diagnostic laparoscopy as the gold standard test. the study protocol was approved by the ethics committee of hamadan university of medical sciences (ethics code: ir.umsha.rec.1397.169). a written informed consent was obtained from patients. the research team was aware of all the provisions of the helsinki declaration on the ethics of medical research including human cases, and fully committed to its observance. 2.2. participants all patients referring to the emergency department of the mentioned hospital following injury by a sharp object to the thoracoabdominal area in the upper boundary of the fourth intercostal space (anterior), the sixth intercostal space (lateral), the eighth intercostal space (posterior) and the lower edge of the ribs, during two years of study, were enrolled. patients who presented with unstable vital signs, had previous history of unrepaired diaphragmatic rupture, were stabbed with a sharp object located outside the thoracoabdominal area, had no evidence of hemothorax or pneumothorax in chest ct scan, had laparoscopy contraindications including history of obstructive pulmonary and cardiovascular diseases, and had generalized peritonitis were excluded. 2.3. study protocol all patients underwent chest ct scan on admission to the emergency department as a triage tool for penetrating thoracoabdominal trauma. patients with negative ct scan were excluded from further investigation. in the presence of hemothorax or pneumothorax in the ct scan, patients were subjected to fast, in which 3 spaces inside the abdomen including morrison space (between the liver and the right kidney), splenorenal space (between the spleen and the left kidney) and the pelvis were examined for the presence of free fluid by a radiologist using a deep probe (2.5-3.5 mhz) of the affiniti 50 ultrasound (phillips, netherlands). presence of fluid in each of these spaces was considered as a positive result of ultrasound. then, all patients underwent a diagnostic laparoscopy in the operating room under general anesthesia. for this purpose, a 10-mm trocar entered the abdomen 1 cm above the umbilicus. after insufflation using 5 liters of carbon dioxide gas, a laparoscopic camera was introduced through the trocar, and all the spaces inside the abdomen and both the diaphragms were examined with direct vision. 2.4. data gathering a questionnaire including information about age, gender, time to reach the emergency department, chest wall laceration length, chest wall laceration location, ct scan result, volume of chest tube fluid, and fast and laparoscopy findings was filled for all enrolled patients. research staff and faculty were responsible for data gathering. 2.5. statistical analysis for reporting qualitative and quantitative data, frequency and percentages and mean ± standard deviation were used, respectively. finally, the non-parametric mann-whitney u test was used to compare the means and the fisher’s exact test was used to compare the qualitative data in spss software version 21. p value of 0.05 or less was considered statistically significant. 3. results 3.1. baseline characteristics of the studied patients twenty-four patients with the mean age of 33 ± 10.64 years (16-61 years) were studied (100% male). table 1 shows baseline characteristics of the studied patients based on the presence or absence of diaphragmatic injury. the mean chest wall laceration size was 2.7 ± 2.7 cm (1-10 cm) and the most frequent location of wounds was posterior chest wall (42%) and in the 6th and 7thintercostal space (50%). chest tube was inserted for all patients, 11 (46%) patients had hemothorax, 7 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e45 (30%) patients had pneumothorax and 6 (24%) patients had hemopneumothorax. the average blood volume discharged from thorax at the time of chest tube insertion was 134 ± 125 cc. 3.2. diagnostic accuracy of ultrasonography all patients were evaluated by fast and free fluid was present in the abdominal cavity of 2 (8.3%) patients. diaphragmatic rupture was seen in 4 (16.7%) patients based on diagnostic laparoscopy, who underwent laparotomy for diaphragmatic rupture repair. in one of these patients, there was a simultaneous spleen laceration with a depth of 0.5 cm without active bleeding, which did not need splenectomy. in another patient, there was a laceration in seromuscular layer of stomach without obvious rupture or leak of content or signs of generalized peritonitis. in the other two patients, except for a diaphragmatic rupture, no other pathologic evidence was found in the abdomen. all patients were discharged from the hospital with good general condition and no mortality occurred. fast had negative findings in all 20 patients whose diaphragm was intact, while the result of fast was positive in 2 of 4 patients (50.0%) with diaphragmatic rupture. based on this findings the sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of fast in detection of diaphragmatic raptures were 50% (95% ci: 9.18 – 90.8), 100% (95% ci: 79.9 – 100.0), 100% (95% ci: 19.8 – 100.0), 9.1% (95% ci: 1.5 – 30.6), infinity, and 0.1 (95% ci: 0.02 – 0.37), respectively. the overall the accuracy of fast in this regard (based on area under the roc curve) was 75.0% (95% ci: 42.3 – 100.0; figure 1). 4. discussion in this study, the prevalence of confirmed diaphragmatic rupture in patients with thoracoabdominal penetrating trauma was reported as 16.7%. the sensitivity and specificity of ultrasonography for diagnosis of diaphragmatic rupture in this study were 50% and 100%, respectively. there was no significant association between mean age, time to reach emergency room, chest wall laceration size, and intercostal space number of penetrating trauma and the rupture of the diaphragm. however, diaphragmatic rupture was more probable in patients with more hemothorax or hemopneumothorax versus those with lower hemothorax volume or hemo/pneumothorax alone. also, the diaphragm rupture rate was significantly higher in patients with penetrating trauma in the lateral chest wall compared to those in the anterior or posterior chest wall. in many studies, the rate of diaphragm rupture in patients with penetrating trauma of the left thoracoabdominal area is reported between 10% and 15% (9, 10). in a study by yucel figure 1: area under the receiver operating characteristic (roc) curve of ultrasonography in detection of diaphragmatic injuries following penetrating trauma. et al. in 2017 in turkey, 81 patients referred to the emergency room with a penetrating trauma of the left thoracoabdominal area and underwent a diagnostic laparoscopy for detection of diaphragmatic rupture during a period of 6 years. similar to our study, 92.6% of the patients were male and average age of the patients was 27.5 ± 9.8 years. left diaphragm rupture was observed in 23.5% of patients. in this study, penetrating trauma to the chest wall was located at the anterior part in 55.5%, the lateral region in 33.3% and the posterior part in 11.2% of patients. unlike our study, in this study, there was no association between the occurrence of penetrating chest trauma and presence or absence of hemopneumothorax with diaphragm rupture (11). in another study by yucel et al. in turkey in 2015, 43 patients with left thoracoabdominal trauma were examined for diaphragmatic rupture with ct scan and diagnostic laparoscopy in a 5-year interval. similar to our study, 91% of patients were male and their average age was 30 years (15-60 years) and left diaphragm rupture was observed in 25.6% of the patients. based on ct scan results, diaphragm was normal in 30 patients and diaphragmatic ruptures were diagnosed in 13. on the other hand, in diagnostic laparoscopy, diaphragmatic rupture was detected in 9 patients of 13 patients with positive ct scan and 2 of 30 patients with negative ct scan. in this study, sensitivity and specificity of ct scan in diagnosis of diaphragmatic rupture were 82% and 88%, respectively, and positive and negative predictive values were 69% and 93%, respectively (12). in a study done by bagheri et al. in iran in 2009 on 30 patients with thoracoabdominal penetrating this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sharifi et al. 4 table 1: baseline characteristics of the studied patients variables total ruptured diaphragm p value yes (n = 4) no (n = 20) age (year) mean ± sd 33 ± 10.64 31.2 ± 5.4 33.3 ± 11.5 0.91 time to reach the hospital (minute) mean ± sd 38.5 ± 16 38.2 ± 16.3 40 ± 16.8 0.73 chest wall laceration length (cm) mean ± sd 2.7 ± 2.2 2.9 ± 2.3 1.6 ± 0.5 0.24 hemothorax volume (ml) mean ± sd 125 ± 134 74 ± 70 380 ± 57 > 0.001 location of wound (in thorax) * posterior 10 (41.7) 0 (0.0) 10 (50.0) anterior 8 (33.3) 1 (25.0) 7 (35.0) 0.009 maxillary 6 (25.0) 3 (75.0) 3 (15.0) location of wound (in intercostal space) * 5th 3 (12.5) 0 (0.0) 3 (15) 6t h 6 (25) 0 (0.0) 6 (30) 7t h 6 (25) 1 (25) 5 (25) 8t h 3 (12.5) 2 (50) 1 (5) 0.013 9t h 2 (8) 1 (25) 1 (5) 10t h 2 (8) 0 (0.0) 2 (10) 11t h 2 (8) 0 (0.0) 2 (10) chest tube drainage* hemothorax 11 (45.8) 0(0.0) 11 (55.0) pneumothorax 7 (29.2) 0 (0.0) 7 (35.0) 0.002 hemo-pneumothorax 6 (25.0) 4 (100.0) 2 (10.0) *data are reported as number (%). wound, 73.3% of the patients were male and their mean age was 26.2 years. similar to our study, the most common location for trauma was in the 6th and 7th intercostal space. similar to our results, 16.7% of patients had a diaphragmatic rupture, and diaphragm rupture was more frequently observed in those with wounds located between 7th intercostal space and lower spaces (3). in a study by mjoli et al. in 2009 in south africa on 55 patients with penetrating thoracoabdominal trauma, 90% of the patients were male, with an average age of 26.3 years. diaphragmatic rupture was seen in 40% of patients. the mean length of chest laceration was 3.1 ± 3.1 cm. the incidence of penetrating trauma to the chest was 41.8% in the lateral, 36.4% in the posterior and 20% in the anterior walls (13). the only study that examined the value of fast in diaphragmatic rupture diagnosis was conducted in the united states in 2004 by tayal et al. in this study, 8 patients with anterior penetrating thoracoabdominal trauma were evaluated using fast and then underwent laparotomy based on the presence of intraperitoneal fluid in fast evaluation. in contrast to our study, sensitivity of 100% (95% confidence interval: 63.1% -100%) and specificity of 100% (confidence intervals of 85.8% -100%) were reported for fast in diaphragmatic rupture diagnosis (14). the difference of sensitivity of fast between this study and our study can be due to the lower number of patients studied or selection of patients with penetrating trauma in the right or left side of the thoracoabdominal area in tayal study. due to the very proximity of the liver to the right diaphragm, the sharp object passing from the right diaphragm following a penetrating trauma to the right thoracoabdominal area definitively causes liver rupture and intra-abdominal hemorrhage, which is associated with positive fast evaluation. fast in patients with penetrating trauma to the left thoracoabdominal cannot be the definitive alternative to diagnostic laparoscopy for detection of diaphragmatic rupture. positive result of fast in such patients suggests diaphragmatic rupture, so that these patients can undergo urgent laparoscopic surgery for diaphragm rupture repair without the need for laparoscopic examination. however, due to the small number of patients in the current study, more studies should be performed on a larger number of patients with penetrating chest trauma to reach a more precise decision about the role of fast in diagnosis of dithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e45 aphragm rupture. 5. limitation one of our limitations was the relatively small sample size of the study. larger studies with more patients might more precisely reveal the issues with using fast in thoracoabdominal stab wound. however, it is suggested to follow-up patients for longer periods to check probable long-term complications. another limitation of this study was operator dependency of fast, which cannot be avoided. fast performed by an expert radiologist might yield different results. 6. conclusion considering the low sensitivity of ultrasonography in detection of diaphragmatic rupture following penetrating trauma to the left thoracoabdominal region, it cannot be the definitive alternative to diagnostic laparoscopy for detection of diaphragmatic rupture. 7. appendix 7.1. acknowledgements we would like to thank the operation room staff of our center. 7.2. author contribution analyzed the data: ali sharifi, amir kasraianfard, soheila kanani; contributed to writing of the manuscript: mohamedali aldarraji, mohammad ali seif-rabiei; final approval and review: abdolhamid chavoshi khamneh, amir derakhshanfar. authors orcids ali sharifi: 0000-0002-4933-2765 amir kasraianfard: 0000-0002-3144-4451 abdolhamid chavoshi khamneh: 0000-0003-0675-3460 soheila kanani: 0000-0002-6058-2271 mohamedali aldarraji: 0000-0002-9937-9107 mohammad ali seif-rabiei: 0000-0003-2722-1703 amir derakhshanfar: 0000-0002-4096-8740 7.3. funding/support none. 7.4. conflict of interest we had no conflict of interest to be reported references 1. edelmuth rc, buscariolli ydos s, ribeiro ma, jr. [damage control surgery: an update]. revista do colegio brasileiro de cirurgioes. 2013;40(2):142-51. 2. boyle em, jr., maier rv, salazar jd, kovacich jc, o’keefe g, mann fa, et al. diagnosis of injuries after stab wounds to the back and flank. the journal of trauma. 1997;42(2):260-5. 3. bagheri r, tavassoli a, sadrizadeh a, mashhadi mr, shahri f, shojaeian r. the role of thoracoscopy for the diagnosis of hidden diaphragmatic injuries in penetrating thoracoabdominal trauma. interactive cardiovascular and thoracic surgery. 2009;9(2):195-7; discussion 7-8. 4. murray ja, demetriades d, cornwell ee, 3rd, asensio ja, velmahos g, belzberg h, et al. penetrating left thoracoabdominal trauma: the incidence and clinical presentation of diaphragm injuries. the journal of trauma. 1997;43(4):624-6. 5. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, haji ghanbari mj, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. emergency (tehran, iran). 2015;3(4):127-36. 6. yousefifard m, baikpour m, ghelichkhani p, asady h, shahsavari nia k, moghadas jafari a, et al. screening performance characteristic of ultrasonography and radiography in detection of pleural effusion; a meta-analysis. emergency (tehran, iran). 2016;4(1):1-10. 7. rahimi-movaghar v, yousefifard m, ghelichkhani p, baikpour m, tafakhori a, asady h, et al. application of ultrasonography and radiography in detection of hemothorax; a systematic review and meta-analysis. 2016;4(3):116. 8. lingawi ss, buckley ar. focused abdominal us in patients with trauma. radiology. 2000;217(2):426-9. 9. cherry ra, eachempati sr, hydo lj, barie ps. the role of laparoscopy in penetrating abdominal stab wounds. surgical laparoscopy, endoscopy & percutaneous techniques. 2005;15(1):14-7. 10. chol yb, lim ks. therapeutic laparoscopy for abdominal trauma. surgical endoscopy. 2003;17(3):421-7. 11. yucel m, ozpek a, tolan hk, basak f, bas g, unal e, et al. importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound: a prospective cohort study. ulusal travma ve acil cerrahi dergisi = turkish journal of trauma & emergency surgery : tjtes. 2017;23(2):107-11. 12. yucel m, bas g, kulali f, unal e, ozpek a, basak f, et al. evaluation of diaphragm in penetrating left thoracoabdominal stab injuries: the role of multislice computed tomography. injury. 2015;46(9):1734-7. 13. mjoli m, oosthuizen g, clarke d, madiba t. laparoscopy in the diagnosis and repair of diaphragmatic injuries in left-sided penetrating thoracoabdominal trauma: laparoscopy in trauma. surgical endoscopy. 2015;29(3):747-52. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. sharifi et al. 6 14. tayal vs, beatty ma, marx ja, tomaszewski ca, thomason mh. fast (focused assessment with sonography in trauma) accurate for cardiac and intraperitoneal injury in penetrating anterior chest trauma. journal of ultrasound in medicine : official journal of the american institute of ultrasound in medicine. 2004;23(4):467-72. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e65 or i g i n a l re s e a rc h incidence and risk factors of clinical deterioration during inter-facility transfer of critically ill patients; a cohort study kannapatch srithong1, siriorn sindhu2∗, napaporn wanitkun3, chukiat viwatwongkasem4 1. dns candidate, faculty of graduate studies, mahidol university, thailand. 2. rn, phd, associate professor, department of surgical nursing, faculty of nursing, mahidol university, thailand. 3. rn, phd, assistant professor, department of surgical nursing, faculty of nursing, mahidol university, thailand. 4. phd, associate professor, biostatistics department, faculty of public health, mahidol university, thailand. received: june 2020; accepted: june 2020; published online: 4 july 2020 abstract: introduction: critically ill and injured patients are at a higher risk of developing clinical deterioration during inter-facility transfers. this study aimed to determine the incidence rate and risk factors of clinical deterioration among critically ill patients during inter-facility transfers in thailand. methods: the present cohort study was conducted in 22 referring hospitals and 7 receiving hospitals under the supervision of ministry of public health, thailand, between march 15 and december 31, 2018. the subjects were comprised of 839 critically ill patients aged 18 and over, 63 coordinator nurses in referral centers, and 312 referral team leaders. data collected included pre-transfer risk score, clinical data of patient during transfer, characteristics of referral team leader, ambulance type, preparation time, time to definitive care, transfer distance, and national early warning score (news) (clinical deterioration). multilevel mixed-effects regression analysis was performed. results: the incidence rate of clinical deterioration was 28.69%. the most common types of clinical deterioration were hemodynamic instability, respiratory instability, and neurological alteration. time between 31-45 minutes was significantly associated with clinical deterioration (β 0.133, p value 0.027). the following illnesses were associated with higher probability of clinical deterioration: body region injuries/head injury/burn/ingested poison (β 0.670, p value 0.030), respiratory distress/convulsion (β 0.919, p value 0.001), shock/ arrhythmias/chest pain/hemorrhage (β 1.134, p value <0.001), comatose/alteration of consciousness/syncope (β 1.343, p value <0.001), and post-cardiac arrest (β 2.251, p value <0.001). patients with unstable conditions (β 1.689, p value 0.001) and pre-transfer risk score of 8 or higher (β 0.625, p value 0.001) had a higher rate of deterioration. transfer by nonemergency room (er) nurses (β 0.495, p value 0.008) and transportation in a mobile intensive care unit (icu) were associated with a higher rate of deterioration (β 0.848, p value 0.001). conclusion: the incidence of clinical deterioration during inter-facility transfer in thailand was high. illnesses involving circulatory, respiratory, and neurological systems, clinical instability, high pre-transfer risk score, transport time of 31-45 minutes, transportation by non-er nurse, and mobile icu were associated with a higher rate of clinical deterioration. keywords: patient transfer; critical illness; clinical deterioration; thailand cite this article as: srithong k, sindhu s, wanitkun n, viwatwongkasem ch. incidence and risk factors of clinical deterioration during inter-facility transfer of critically ill patients; a cohort study. arch acad emerg med. 2020; 8(1): e65. ∗corresponding author: siriorn sindhu; faculty of nursing, mahidol university, bangkok, thailand. no. 2 wang lang road, siriraj, bangkoknoi, bangkok 10700, thailand, email: siriorn.sin@mahidol.edu, phone: +668-1817-6060, fax: +662-412-8415. 1. introduction clinical deterioration, including cardiac arrest, can occur during inter-facility transfer of critically ill patients. recent evidence on the incidence rate of clinical deterioration during inter-facility transfer is quite limited. two studies conducted in the netherlands reported incidence rates between 15.2 and 34.0% (1, 2). two studies in canada and saudi arabia reported the incidence rates of 6.5% and 13.6%, respecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. srithong et al. 2 tively (3, 4). a number of risk factors for inter-facility clinical deterioration have been examined in international literature. these factors can be classified into patient-related factors and service-related factors (1-5). clinical deteriorations have been found to be associated with age, sex, clinical conditions, and level of patient acuity (4, 5). increasing age, being male, sustaining illnesses involving circulatory, respiratory, and neurological systems, and having high acuity increase the risk of clinical deteriorations. the service factors included pre-transfer risk score, duringtransfer care, characteristics of referral team leader, ambulance type, preparation time, time to definitive care, and transfer distance (1-4, 6). higher pre-transfer risk score predicts higher probability of clinical deterioration (3, 6). patients receiving appropriate management until achieving clinical stabilization before transfer are less likely to experience clinical deterioration (4, 5, 7). during-transfer care includes assessment and monitoring of the patient as well as interventions given to the patient. in the netherlands, ligtenberg et al. (2006) reckoned that the lack of during-transfer care protocols contributed to high incidence of clinical deterioration (1). a subsequent dutch study, which incorporated a during-transfer protocol, reported a much lower incidence rate for clinical deterioration (2). during the transfer, patients managed by doctors, nurses, and paramedics who underwent critical care transport training were less likely to experience clinical deterioration (2, 3). patients being transported in an ambulance fully equipped with critical care technologies (i.e., mobile intensive care unit (icu)) were less likely to experience clinical deterioration (2, 7). increasing preparation time, time to definitive care, and transfer distance increase clinical deterioration incidence (4). recent studies have not found an association between clinical deterioration and post-transfer outcomes such as icu admission and death (3, 8). this may be due to limitations related to sampling and outcome measurement. nonetheless, in hospitalized patients, clinical deterioration is often associated with more serious health outcomes such as icu admission and death. clinical deterioration is still an issue of great concern. approximately 52-91% of clinical deterioration incidents are preventable. clinical deterioration can be prevented via early detection (9). early detection of clinical deterioration leads to timely management of deteriorating changes and therefore, prevents progression to fatal events such as cardiopulmonary arrest. in developed countries, inter-facility transfer of critically ill patients is carried out either by well-equipped ambulance centers or tertiary care hospitals (2, 7, 10-12). staff responsible for transporting the patients in these countries must undergo critical care transport training to ensure suitable knowledge and skills in managing patients’ conditions and clinical deterioration (2, 3). in thailand, transfers of critically ill patients is carried out by resource-limited community hospitals. these resource-deprived community hospitals rely on emergency room (er) nurses and non-er nurses with varying qualifications and experiences when transporting the patients. the majority of these nurses do not have formal training in inter-facility transfer. lack of knowledge and skills among the referring nurses can compromise the ability of nurses in detecting early warning signs, managing deterioration, and preventing and managing these conditions during the transfer. variations in patient transfer structures, practices and outcomes can be expected due to varying material and human resources as well as the lack of consensus practice guidelines among these hospitals. since clinical deterioration during the transfer can be harmful, data about its incidence and risk factors are important for health policymakers and practitioners to understand the situation and note gaps in existing inter-facility transfer services. such knowledge is needed for evidence-based decision making to improve regulations, structural support, and human resource development to improve early detection, prevention, and management of patient deterioration during the transfer. this cohort study aimed to determine the incidence and risk factors of inter-facility transfer clinical deterioration. 2. methods 2.1. study design and setting this cohort study took place in thailand, between march 15 and december 31, 2018. stratified random sampling was used. seven health service networks were randomly selected from 12 networks (excluding bangkok metropolitan administration). seven provinces were then selected from these networks. based on the proportion, two to six community hospitals within these provinces were then randomly recruited into the study as referring hospitals. in case there were more than one receiving hospitals in the province, the most advanced hospital was selected as receiving hospital. the study involved 22 referring hospitals and 7 receiving hospitals under the supervision of ministry of public health across thailand. this study concerned only inter-facility transfers that took place within the province (i.e., intra-province transfers). transfers between provinces were not included in this study. the study protocol was approved by the institutional review board, faculty of nursing, mahidol university (no: irbns2017/423.2512). to comply with local human research ethics requirements, additional ethics approvals were also sought from seven receiving hospitals before the commencement of the study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e65 2.2. participants critically ill patients, referring nurses, and coordinator nurses comprised the study samples. the patient sample size calculation was based on power of analysis, level of significance, effect size, intraclass correlation (icc) coefficient, and possible sample size of the participants (13). first, we determined the effect size (d) based on data from the previous study on inter-facility transfer (14) with power of analysis and level of significance of 0.80 and 0.05, respectively. second, we determined the sample size of the referring hospitals based on the desired intra-class correlation (icc) of 0.30 and the expected sample size of 30 patients per hospital. the calculation resulted in the referring hospital sample size of 22. the patient sample size was, therefore, 660 (i.e., 30 x 22). to deal with potential loss of data, we increased the sample size by 30% or 198 patients. after rounding up, the final sample size was 880. 2.3. inclusion and exclusion criteria patients to be included in the study, the patients had to be at least 18 years of age, treated in the emergency room at referring hospitals, and critically ill as per patient acuity classification. patients diagnosed with psychiatric and obstetric emergencies were excluded. referring and coordinators nurses as per the national clinical practice guideline, at least two health practitioners are assigned to the transfer of critically ill patients. only the nurses who were designated as team leader of the inter-facility transfer team were included in the study regardless of their experience and qualifications. coordinator nurses who were on duty at the receiving hospitals during the transfer were included. 2.4. variables independent variables measurement independent variables included patient sex and age, level of patient acuity, clinical signs and symptoms, and pre-transfer risk score, referring nurse’s qualification, referring nurse’s experience, preparation time, type of ambulance, duringtransfer reassessment, transfer distance, transfer time, and time to definitive treatment. pre-transfer risk score was assessed using risk score of interhospital transport of critically ill patients (rstp) (6). an rstp score of 8 or higher was considered as an indication of high risk for clinical deterioration. inter-rater reliability of rstp among the researcher and 14 research assistants was 0.83 based on kappa coefficient (15). nurse’s qualifications were described as emergency nurse practitioner (enp), er nurse, and non-er nurse. nurse’s inter-facility transfer experience was measured as number of years involved in interfacility transfer (ift). preparation time was the duration between the time when the patient first presented to er to the time when referral decision was made. time to definitive treatment was the duration between the time when the referral decision was made to the time when the patient received treatment at the receiving hospital. these times were measured in minutes. transfer distance was the distance between referring hospital and receiving hospital and was measured in kilometers. content validity of other instruments was obtained through a panel of experts. these data were collected from inter-facility transfer records from referring and receiving hospitals as well as on the ambulance. outcome measurement the studied outcome was clinical deterioration. the following clinical conditions occurring during the transfer was defined as incidence of clinical deterioration: systolic blood pressure (sbp) < 90 mmhg or > 160 mmhg, spo2 < 92% for intubated patients or < 90% or baseline reduction ≥ 5% in adults, respiratory rate ≥ 26 bpm or ≤ 10 bpm, heart rate ≥ 140 bpm or ≤ 40 bpm, increased chest pain, arrhythmias, cardiac arrest, a drop in glasgow coma score ≥ 2, and convulsion. patients who experienced any of the above-mentioned conditions at any given time during the transfer were regarded as having clinical deterioration. the national early warning score (news) was used to assess changes in clinical deterioration score. internationally, clinical deterioration can be detected using different tools such as rapid emergency medicine score (rem), early warning score (ews), risk score for transfer patient (rstp), modified early warning score (mews), therapeutic intervention scoring system (tiss-28), and national early warning score (news) (6, 1619). among these instruments, news is the most effective in predicting serious clinical deterioration and was found to be sensitive to cardiopulmonary arrest (19). this study, therefore, used news to assess patient deterioration. the score was derived from the assessment of 7 physiological parameters as follows: respiratory rate, oxygen saturation, supplemental oxygen, temperature, systolic blood pressure, heart rate, and level of consciousness (19, 20). news parameters were recorded by referring nurse in the patient transfer form at six different time intervals throughout the transfer, namely, 1-15 minutes, 16-30 minutes, 31-45 minutes, 46-60 minutes, 61-75 minutes, and 76-90 minutes. the researcher and research assistants then retrieved the data from the record form. 2.5. statistical analysis multilevel mixed-effects linear regression analysis was done using stata statistical software version 16.0. findings were presented as a model of factors predicting clinical deterioration during inter-facility transfer. p values less than 0.05 were considered statistically significant. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. srithong et al. 4 table 1: baseline characteristics of studied patients variable values patient demographics sex male 509 (60.67) female 330 (39.33) age (year) mean ± sd (range) 59.57±18.00 (18-99) clinical signs and symptoms of illness (a) hemiplegia/paraplegia/severe pain/high fever 110 (13.11) (b) body region injuries/head injury/burn/ingested poison 113 (13.47) (c) respiratory distress/convulsion 280 (33.37) (d) shock/arrhythmia/chest pain/hemorrhage 202 (24.08) (e) comatose/alteration of consciousness/syncope 95 (11.32) (f ) post cardiac arrest 39 (4.65) patient acuity level stable with medium risk of deterioration 34 (4.05) stable with high risk of deterioration 707 (84.27) unstable with clinical deterioration 98 (11.68) pre-transfer risk score low risk (≤7 scores) 330 (39.33) high risk (≥8 scores) 509 (60.67) mean ± sd (range) 8.00±2.61 (0-20) inter-facility service demographics transfer team leader’ qualification (n=312) non-er nurse 98 (31.41) er nurse 173 (55.45) enps or ens 41 (13.14) transfer team leader’s experience (year) mean ± sd (range) 9.51±7.54 (1-36) ambulance types ems ambulance 622 (74.14) mobile icu ambulance 217 (25.86) during transfer reassessment more than 15 minutes 306 (36.47) every 5-15 minutes 533 (63.53) preparation time (minutes) mean ± sd (range) 72.10±28.35 (12-120) time to definitive treatment (minute) mean ± sd (range) 52.38±21.97 (16-170) transfer distance (kilometer) mean ± sd (range) 59.97±28.31 (8.9-110.0) data are presented as mean ± standard deviation (sd) or frequency (%). er: emergency room, enp: emergency nurse practitioner, en: emergency nurse, ems: emergency medical service, icu: intensive care unit. 3. results 3.1. baseline characteristics of inter-facility transfer system 839 critically ill patients comprised the final patient sample in this study. the majority were male (60.67%). the mean age was 59.57 ± 18.00 (18 99) years. the majority suffered from critical illnesses involving circulatory and respiratory systems (57.45%) and were classified as stable with high risk of deterioration (84.27%). 60.67% of the patients were considered as having a high risk for clinical deterioration. the majority of referring team leaders were er nurses (55.45%). the mean inter-facility transfer experiences were 9.51 ± 7.54 (<1-36) years. the mean preparation time and time to definitive treatment were 72.10 ± 28.35 (12-120) and 52.38 ± 21.97 (16-170) minutes, respectively. transfer distance was 52.97 ± 28.31 (8.9-110.0) kilometers. 3.2. clinical deterioration the incidence of clinical deterioration during inter-facility transfer was 28.37% (n = 238/839). unstable patients had a higher rate of clinical deterioration (63.27%; n = 62) compared to stable patients with a high risk of deterioration (24.33%; n = 172) and stable patients with a medium risk of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e65 deterioration (11.76%; n = 4). overall, the average news of critically ill patient sample during each timeframe was between 4.57 to 4.90. the news of individual patients ranged from 0 to 20. the highest average score was 4.90 ± 2.77, which was measured during 31-45 minutes. considering clinical stability, stable patients with high risk of deterioration had an average news between 4.69 and 4.92 with the highest average score of 4.92 ± 2.80 at 76-90 minutes. high average news (between 6.35 and 7.12) was observed among unstable patients with the highest average score of 7.12 ± 3.20 at 46-60 minutes. 3.3. predictors of clinical deterioration during transfer the following variables, which were found to have significant association (p value < 0.25) with clinical deterioration in a univariate analysis, were included in subsequent multilevel mixed-effects linear regression analysis: patient sex, clinical signs and symptoms of illnesses, patient acuity level, pretransfer risk score, transfer team leader’s qualification, transfer team leader’s experience, during transfer reassessment, ambulance types, preparation time, time to definitive treatment, and transfer distance. in this study, individual patients with critical illness had an average news of 2.403 throughout the transfer. clinical signs and symptoms involving circulatory, respiratory, and neurological systems, unstable conditions, pre-transfer high risk score, transfer by non-er nurses, transport by mobile icu, and 31-45 minutes transfer timeframe were found to be associated with a significant increase in news (table 3). 4. discussion this study examined clinical deterioration of critically ill patients during inter-facility transfer. the inter-facility clinical deterioration rate was 28.37% (n = 238). symptoms of clinical deterioration could be classified into hemodynamic instability, respiratory instability, and neurological alteration. the classification resembled previous studies in canada, saudi arabia, and australia (3, 4, 10). the major results described patient, service, and timerelated factors associated with patient deterioration as measured by news. illnesses involving circulatory, respiratory, and neurological systems significantly increased clinical deterioration incidences when compared with motor deficit/severe pain/high fever. unstable conditions significantly increased news by 1.689 compared with stable conditions with a medium risk of deterioration. high pre-transfer risk score (≥ 8) significantly increased the news by 0.625 compared with low pre-transfer risk score (≤ 7). a significant increase of news by 0.133 was found 31-45 minutes after transfer when compared with news before transfer. transfer by non-er nurses increased the news by 0.495 when compared to the transfer by er nurses. transfer by mobile icu increased news by 0.848 when compared with transfers by standard ambulance. in our study, it is clear that patients having circulatory, respiratory, and neurological illnesses, unstable clinical conditions and pre-transfer risk score were more likely to experience clinical deterioration during the transfer. in a previous study by alabdali et al. (2017), cardiac patients were less likely to develop clinical deterioration (adjusted or: 0.117, 95% ci: 0.02 to 0.52 and p value <0.01) (3). in another study, cardiac patients (crude or: 0.6, 95% ci: 0.4 to 0.8), neurologic patients (crude or: 0.4, 95% ci: 0.3 to 0.6), and trauma patients (crude or: 0.5, 95% ci: 0.3 to 0.8) were less likely to develop clinical deterioration (4). our findings appear to contradict with previous studies. it is, however, of note that the way we categorized patients’ illness in this study differed from that of the previous two studies. our study used clinical signs and symptoms as a basis for illness categorization whereas the previous studies relied on medical diagnoses. clinical signs and symptoms and medical diagnoses are not always the same. patients with cardiac diagnosis, for example, do not always present with cardiac signs and symptoms. this also applies to patients with neurologic and trauma diagnoses. we believe that clinical signs and symptoms better reflect patient conditions and needs, since they change during critical illness unlike medical diagnosis. clinical signs and symptoms offered a better basis for illness categorization as they were more sensitive to clinical deterioration as evident in this study; whereas, medical diagnoses were not. in addition, clinical signs and symptoms help guide appropriate interventions related to physiological changes, which are common in critically ill patients. patient acuity and pre-transfer risk score could predict patient deterioration during the transfer. this is not surprising as these variables were derived from data concerning clinical deterioration, for example, low blood pressure, low heart rate, decreased level of consciousness, increased respiratory rate, oxygen desaturation, and cardiac arrest. our findings were consistent with previous studies in canada, saudi arabia, and hong kong (3-5). lee et al. (2010) reported that physiological instability before the transfer was a significant risk factor of clinical deterioration (p value 0.004). singh et al. (2014) reported that patients with baseline hemodynamic instability were more likely to develop clinical deterioration during the transfer (crude or: 3.9, 95% ci: 3.1 to 4.9). alabdali et al. (2017) reported that patients with pre-transfer risk score of 6 or higher were 1.3 times more likely to experience clinical deterioration. our study has confirmed that patient acuity and pre-transfer risk score were predictive of clinical deterioration, and thus can be used as tools to anticipate changes in patient conditions and plan for proper prethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. srithong et al. 6 table 2: national early warning score (news) classified by time of measurement and patient acuity level news (0-20) time of measurement time 0 before transfer time 1 1-15 minutes time 2 16-30 minutes time 3 31-45 minutes time 4 46-60 minutes time 5 61-75 minutes time 6 76-90 minutes total critically ill patients (n=839) (n=839) (n=776) (n=657) (n=497) (n=258) (n=80) mean ± sd 4.70±2.66 4.74±2.75 4.73±2.76 4.90±2.77 4.84±2.85 4.57±2.70 4.86±3.02 range (0 to 14) (0 to 18) (0 to 18) (0 to 20) (0 to 20) (0 to 15) (0 to 13) stable with medium risk of deterioration (n=34) (n=34) (n=32) (n=25) (n=25) (n=16) (n=4) mean ± sd 0.00±0.00 0.21±0.64 0.31±1.00 0.32±1.14 0.24±1.01 0.00±0.00 0.00±0.00 range (0) (0 to 3) (0 to 4) (0 to5) (0 to 5) (0) (0) stable with high risk of deterioration (n=707) (n=707) (n=662) (n=564) (n=422) (n=222) (n=66) mean ± sd 4.64±2.43 4.69±2.05 4.74±2.59 4.89±2.56 4.84±2.53 4.74±2.44 4.92±2.80 range (3 to 13) (2 to 13) (3 to 17) (3 to 17) (3 to 17) (2 to 15) (3 to 13) unstable with clinical deterioration (n=98) (n=98) (n=82) (n=68) (n=50) (n=20) (n=10) mean ± sd 6.67±2.56 6.72±2.90 6.35±2.74 6.68±2.91 7.12±3.29 6.40±2.87 6.40±3.20 range (3 to 14) (3 to 18) (3 to 18) (4 to 20) (4 to 20) (3 to 11) (3 to 13) sd: standard deviation. vention and management during the transfer. only one study identified the effect of time on clinical deterioration. clinical deterioration increased 1.15 times for each additional 10 minutes of transport time (4). longer ride leads to accumulative effects of physiological changes associated with vibrations and inertial force during ambulance moving and these effects can contribute to the occurrence of deterioration (11). acceleration, deceleration, and vibrations in a moving car are associated with hemodynamic changes. these changes include low blood pressure, interference with blood flow to the brain, and increased heart rate and respiratory rate (12). our study also found the effect of time on clinical deterioration. however, a significant increase of news was found only 31-45 minutes after departure when compared with departure time. upon close examination, we found that the increase in news 31-45 minutes after departure was due to the occurrence of serious clinical deterioration due to cardiac arrest, hypotension, oxygen desaturation, and alteration of consciousness in this period. why these serious events occurred more frequently during this period warrants explanation. due to limited knowledge about this occurring, we attempt to hypothesize this for future research. first, the adverse effects of certain medical treatments received at the referring hospital may fall within this period. such treatments are, for example, thrombolytic agent and bronchodilator. peak of action of bronchodilator is between 30-60 minutes. the adverse reactions that can present during this time frame include palpitation, hypertension, tachycardia, chest pain, dyspnea, and paradoxical bronchospasm. streptokinase, is known to induce arrhythmias and hypotension, which normally occur during the first 15-30 minutes after infusion. in thailand, streptokinase is infused for patients with myocardial infarction at the referring community hospital before departure. currently there are two common practices regarding streptokinase infusion. first, the referring hospital completes the infusion before commencing the transfer. second, the referring hospital commences the transfer immediately after starting the infusion. the latter practice might lead to more frequent occurrence of clinical deterioration due to unmanaged adverse drug reactions during the early stages of transfer. another explanation concerns the sustainability of therapeutic effects of medical treatments received at the referring hospital. for example, optimal blood pressure in patients with septic shock and trauma can be achieved through fluid resuscitation in er. however, this resuscitative effect is best seen during the first 30 minutes and only lasts for 60 minutes. this may reintroduce clinical instability (i.e., hypotension) during transfer, especially when there is no or inadequate intervention to maintain optimal hemodynamics. our data showed that a number of critically ill patients developed new and recurrent clinical deterioration throughout the transfer. the patients transferred by non-er nurses were more likely to experience clinical deterioration compared to those transferred by er nurses and enps. as per the quality mandate in thailand, all er nurses must undergo compulsory advanced life support annually. in-house trainings related to pre-hospital care, inter-facility transfer and mass casualty management were also very common among these nurses. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e65 table 3: multilevel mixed-effects analysis to predict clinical deterioration variables multivariable analysis β 95%ci p value fixed effect intercept (β0 ) 2.403 (1.580–3.226) <0.001 news score during-transfer time time 0 (before transfer) ref. time 1 (1-15 minutes) 0.037 (-0.071–0.145) 0.504 time 2 (16-30 minutes) 0.104 (-0.007–0.216) 0.067 time 3 (31-45 minutes) 0.133 (0.015–0.251) 0.027* time 4 (46-60 minutes) 0.106 (-0.025–0.236) 0.112 time 5 (61-75 minutes) 0.009 (-0.158–0.176) 0.918 time 6 (76-90 minutes) 0.242 (-0.036 0.520) 0.087 clinical signs and symptoms of illness (a) hemiplegia/paraplegia/severe pain/high fever ref. (b) body region injuries/head injury/burn/ingested poison 0.670 (0.065–1.274) 0.030* (c) respiratory distress/convulsion 0.919 (0.371–1.467) 0.001* (d) shock/arrhythmias/chest pain/hemorrhage 1.134 (0.569–1.698) <0.001* (e) comatose/alteration of consciousness/syncope 1.343 (0.661–2.026) <0.001* (f ) cardiac arrest 2.251 (1.175–3.328) <0.001* patient acuity level stable with medium risk of deterioration ref. stable with high risk of deterioration 0.651 (-0.172–1.475) 0.121 unstable with clinical deterioration 1.689 (0.663–2.715) 0.001* pre-transfer risk score rstp ≤7 scores ref. rstp ≥ 8 scores 0.625 (0.269–0.981) 0.001* referral team leader er nurses ref. non-er nurses 0.495 (0.132–0.857) 0.008* enps or ens 0.064 (-0.519–0.647) 0.829 ambulance type standard ambulance ref. mobile icu 0.848 (0.349–1.347) 0.001* * significant p value. news: national early warning score; rstp: risk score for transport patients, er: emergency room; enp: emergency nurse practitioner, en: emergency nurse, icu: intensive care unit; ref.: reference. in addition, er nurses were involved in inter-facility transfers on a much more regular basis than non-er nurses. the enps, on the other hand, completed a four-month intensive training program plus continuing staff development activities undertaken by er nurses. this set of knowledge and skills acquired through trainings and experiences made the er nurses and enps more efficient in managing critically ill patients during the transfer, compared to non-er nurses who rarely underwent these trainings and infrequently attended to critically ill patients. our finding was consistent with those described in previous studies. patients transferred by paramedics with training in critical care transport experienced clinical deterioration significantly less than those transferred by paramedics without critical care transport (3). this finding was indicative of the role of knowledge and skills of transferring personnel in prevention and management of clinical deterioration. this study was the first to examine the role of ambulance type on clinical deterioration. our original hypothesis was that patients transferred by standard ambulance would be at higher risk of experiencing clinical deterioration than those transferred by a mobile icu. to our surprise, the result was the opposite. our study revealed that transfer by mobile icu ambulance increased news by 0.848 when compared to transfer by standard ambulance. we reckon that the increase in clinical deterioration rate in mobile icu ambulance reflected the detectability rather than the actual occurrence of clinical deterioration. in a standard ambulance with no continuous monitoring, it was likely that fewer signs of clinical deterioration were detected and recorded than they actually occurred. continuous monitoring in mobile icu ambulance facilitated rapid detection and documentation of abnormal changes in physiologic parameters such as heart rate, respiration, blood pressure and oxygen saturation. sex and age of the patients, preparation or resuscitation time, frequency of patient reassessment during transfer, interthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. srithong et al. 8 facility transfer experience of nurses, transfer distance, and time to definitive treatment were not found to be associated with clinical deterioration. we expected to find the association between age and clinical deterioration as in a previous study (4), however, our result was different. sex was not also associated with clinical deterioration. these variables might have served as confounders in this study. referral experience of nurses, which was measured as number of years involved in inter-facility patient transfer was not associated with clinical deterioration. preparation time was not associated with the increase in news despite our previous understanding that preparation time could suggest patient severity, which would result in higher probability of subsequent deterioration. in the thai contexts, referring hospitals are expected to stabilize the patient before they initiate the transfer. this preparation period may be short or long, depending on whether the patients achieve stabilization goals. preparation time was, therefore, not an important factor in determining patient safety (i.e., clinical deterioration) but achievement of stable conditions before departure was. for us, the number of years in inter-facility transfer did not equate expertise in inter-facility transfer, which was found to affect clinical deterioration incidence. this is especially true for non-er nurses who did not have enough training and were put in charge of patient transfer once in a while, even though they had been involved in inter-facility transfer for a number of years. it is, therefore, important that we consider expertise but not the number of practice years when choosing nurses for patient transfer. the canadian study revealed the effect of transfer distance on clinical deterioration (4). in our study, the distance was not associated with clinical deterioration. the longest distance in this study, which concerned only within-provincial transport, was 110 kms; whereas, the shortest was 8.9 kms. from the result, we could only say that the increase in distance did not increase clinical deterioration incidence, when the distance was between 8.9-110 kms. it is of practical note to point out that patient transport involving distances longer than 110 kms, as in inter-provincial transport, may not be as safe. the longer distance might produce different results (i.e., increase in clinical deterioration) and system redesign may be needed to ensure safety during transport in such situations. this is, however, subject to further investigation. the increase in time to definitive treatment did not increase news. all the patients in this study reached the receiving hospitals within 170 minutes since the referring hospital contacted the receiving hospital for referral. again, we could only say that this timeframe did not result in a higher rate of clinical deterioration. further study is required to determine whether it is still as safe beyond this timeframe, or not. clinical deterioration during inter-facility transfer of critically ill patients can be better prevented and managed by pre-departure assessment of clinical deterioration risks using associated clinical parameters such as patient acuity and signs and symptoms, adequate stabilization of the patients, designation of enp or er nurses as transfer leader, close monitoring of deteriorating signs through mobile icu, and continuing management during transport. 5. limitation limitations concerning the completeness of clinical data recorded during transfer might have been present. despite our briefing on documentation requirements, variations in nurses’ knowledge and skills could have impacted the quality of documentation and thus, quality of the data collected. 6. conclusion the incidence of clinical deterioration during inter-facility transfer of critically ill patients between community hospitals and provincial hospitals in thailand was 28.7%. patients with signs and symptoms involving circulatory, respiratory, and neurologic systems, unstable clinical conditions, and high pre-transfer risk scores were at risk of experiencing clinical deterioration. achievement of stabilization before departure, regardless of preparation time, was a safe practice. patients transferred by enps did not experience an increase in clinical deterioration rate; whereas, those managed by noner nurses did. mobile icu detected more deterioration incidents than standard ambulances. an increase in clinical deterioration rate could be expected 31-45 minutes after departure from the referring hospital. a timeframe between 16-170 minutes and transfer distance between 8.9-110 kms did not cause any differences in clinical deterioration rate. within the context of our study, these time and distance limits were, therefore, considered reasonably safe for patient transport. 7. declarations 7.1. acknowledgements we thank all the study participants for taking part in this study as well as health professionals for their facilitation during data collection. 7.2. author contribution all the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. authors orcids kannapatch srithong: 0000-0003-1535-543x siriorn sindhu: 0000-0001-9326-757x napaporn wanitkun: 0000-0002-0512-1368 chukiat viwatwongkasem: 0000-0003-4918-2717 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e65 7.3. funding/support no funding and support were received for this study. 7.4. conflict of interest the authors declared that they have no potential conflicts of interests with respect to the research, authorship, and/or publication of this article. references 1. ligtenberg jjm, arnold lg, stienstra y, van der werf ts, meertens jhjm, tulleken je, et al. quality of interhospital transport of critically ill patients: a prospective audit. crit care. 2005;9(4):r446. 2. van lieshout ej, binnekade j, reussien e, dongelmans d, juffermans np, de haan rj, et al. nurses versus physician-led interhospital critical care transport: a randomized non-inferiority trial. intensive care med. 2016;42(7):1146-54. 3. alabdali a, trivedy c, aljerian n, kimani pk, lilford r. incidence and predictors of adverse events and outcomes for adult critically ill patients transferred by paramedics to a tertiary care medical facility. j health spec. 2017;5(4):206. 4. singh jm, macdonald rd, ahghari m. critical events during land-based 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ligtenberg jjm, zijlstra jg. transferring the critically ill patient: are we there yet? crit care. 2015;19(1):62. 10. fan e, macdonald rd, adhikari nk, scales dc, wax rs, stewart te, et al. outcomes of interfacility critical care adult patient transport: a systematic review. crit care. 2005;10(1):r6. 11. atotw 330-physiological effects of transfer for critically ill patients [internet]. 2016 [cited 28th june 2017]. available from: https://www.wfsahq.org/components/com_virtual_libr ary/media/e25fd136d2b7ebef4092cd6b949dab52330-physiological-effects-of-transfer-for-critically-illpatients.pdf. 12. ambulance services, reliability problems and potential technologies [internet]. 2010 [cited 28th octpber 2018]. available from: https://web.wpi.edu/pubs/eproject/available/e-project-042910085147/unrestricted/iqp_for_submissionlin.pdf. 13. scherbaum ca, ferreter jm. estimating statistical power and required sample sizes for organizational research using multilevel modeling. organizational research methods. 2009;12(2):347-67. 14. faine ba, noack jm, wong t, messerly jt, ahmed a, fuller bm, et al. interhospital transfer delays appropriate treatment for patients with severe sepsis and septic shock: a retrospective cohort study. crit care med. 2015;43(12):2589-96. 15. mchugh ml. interrater reliability: the kappa statistic. biochem med (zagreb). 2012;22(3):276-82. 16. groarke jd, gallagher j, stack j, aftab a, dwyer c, mcgovern r, et al. use of an admission early warning score to predict patient morbidity and mortality and treatment success. emerg med j. 2008;25(12):803-6. 17. imhoff bf, thompson nj, hastings ma, nazir n, moncure m, cannon cm. rapid emergency medicine score (rems) in the trauma population: a retrospective study. bmj open. 2014;4(5):e004738. 18. lee lly, yeung kl, lo wyl, lau ysc, tang syh, chan jts. evaluation of a simplified therapeutic intervention scoring system (tiss-28) and the modified early warning score (mews) in predicting physiological deterioration during inter-facility transport. resuscitation. 2008;76(1):47-51. 19. smith gb, prytherch dr, meredith p, schmidt pe, featherstone pi. the ability of the national early warning score (news) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. resuscitation. 2013;84(4):465-70. 20. royal college of physicians. national early warning score (news): standardising the assessment of acuteillness severity in the nhs. report of a working party. london: royal college of physicians; 2012. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2019; 7 (1): e68 or i g i n a l re s e a rc h what victims of domestic violence experience in emergency departments; a cross sectional study brieana rodriguez1, madalyn mandich1∗ 1. medical college of wisconsin, milwaukee, wisconsin, usa. received: september 2019; accepted: october 2019; published online: 24 november 2019 abstract: introduction: domestic violence (dv ) is a problem defined as physical, sexual, and/or mental abuse used by one person in a relationship in order to gain control over the other. this study aimed to investigate what victims of domestic violence are experiencing when they present to the emergency department (ed). methods: the survey was conducted during the women’s initial visit to sojourner family peace center (sfpc) in milwaukee, wi. it included 22 questions assessing women’s encounters with screening and treatment for domestic violence in the ed. results: 24 surveys were collected over 7 months. thirteen women presented for treatment of injuries related or not related to abuse. problems with abuse-related care they received were identified. 31% of women presenting with obvious signs of abuse, such as human bite wounds or head injury, were not screened. four of 11 women were screened with family or law enforcement present. nine of 11 were screened by a nurse, social worker, or police officer, not a physician. four women felt rushed by healthcare professionals and that they did not genuinely care. most noticeably, women were not screened at all. conclusion: dv screening must be done with no family present. removing law enforcement from rooms is noted to make women feel more comfortable. if a family member is adamant about remaining with the patient, the patient can be removed for a blood draw or sensitive exam to attain privacy. standardizing screening could aid in making dv victims feel less rushed and more at ease. the courageous women sharing personal stories help pave the way to better treatment for future victims of dv presenting to the ed. keywords: domestic violence; emergency service, hospital cite this article as: rodriguez b, mandich m. what victims of domestic violence experience in emergency departments; a cross sectional study. arch acad emerg med. 2019; 7(1): e68. 1. introduction domestic violence is a continuing and devastating problem defined as physical, sexual, and/or mental abuse used by one person in a relationship in order to gain control over the other. over 10 million people in the united states will experience domestic violence at some point in their lifetime, and an estimated 34% will seek medical care for their injuries (1). domestic violence victims seeking care will likely present to primary care clinics, urgent care clinics, ob/gyn clinics, eds, and almost every other specialty for treatment and help. domestic violence is an issue all healthcare professionals will encounter at some point throughout their career. it is imperative that healthcare professionals are trained to adequately and respectfully identify and treat patients present∗corresponding author: madalyn mandich; 8365 watertown plank road, wauwatosa, wi 53213, wisconsin, usa. email: mmandich@mcw.edu. tel: 001(262) 501-9980 ing to them for domestic violence related health problems. this is an issue so vital that the joint commission (2), the american college of emergency physicians (3), and the us preventive services task force (4) have strongly encouraged screening for domestic violence. however, even after years of medical organization’s advocacy, only about 30% of women who presented to the emergency department have actually been screened (5). this is in contrast to physicians caring for pregnant women who report routine screening 11-39% of the time, no matter the healthcare setting (6). numerous factors play a role in this process and all need to be taken into consideration when screening for this sensitive topic. for example, it must be taken into account where the conversation takes place, how it takes place, and the appropriate response or follow up to anything a domestic violence victim discloses. studies have shown that this process, which is supposed to be meaningful and private, is often hindered by having a third party present, lack of referral and appropriate resources, and lack of empathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rodriguez et al. 2 thy (7). in order to gain a better understanding of this process and the pitfalls that are continuing to occur, it is timely and of critical importance to get the perspective of the women who are in this vulnerable position. previous studies involving targeted interventions toward pregnant and postpartum women found decreased episodes of domestic violence, reduced reproductive coercion, and improved birth outcomes (6). this evidence of a positive effect of domestic violence screening in an obstetrics setting warrants further investigation in the ed setting as they are often the healthcare setting that victims initially present to for care, safety, and treatment. in addition, the unique characteristics of the ed setting call for both helping victims, as well as, taking extra caution to provide such care due to the acute nature of the visit. due to this, focusing on the ed will provide valuable information that can set a basis for all other healthcare settings when screening for domestic violence. for the above-mentioned reasons, this study aimed to ivestigate what victims of domestic violence are experiencing when they present to the ed. 2. methods 2.1. study design and setting this cross sectional study was conducted from november 2018 to june 2019 on the clients of sojourner family peace center in milwaukee, wi, who reported presenting to the ed for abuse-related or non-abuse-related services. sojourner family peace center is the largest nonprofit provider located in wisconsin, serving over 9,500 victims each year (8). they offer resources, such as helping obtain a restraining order and providing a case manager, that help women affected by domestic violence receive justice. in addition to legal help, they also offer an ample amount of references and followup care to aid women in gaining independence and selfsufficiency once they leave the safety and shelter of sojourner family peace center. due to the significant amount of care sojourner family peace center provides to the women of southeastern wisconsin, we decided to partner with them in order to gain first-hand insight into what victims of domestic violence are experiencing when they present to the ed through a 22 questions survay. in order to keep the data secured and to protect confidentiality, no personal health information was stated on the survey. the information gathered was anonymous and any woman who had not previously presented to the emergency department was excluded. the methods of study were reviewed and approved by the institutional review board, and the data from this study will be used to develop recommendations for improving ed treatment of domestic violence victims. 2.2. participants all females aged 18 years and older who presented to sojourner family peace center for an initial interview process, regardless of whether or not they had ever presented to an emergency department for treatment of injuries sustained due to domestic violence, were included. this is in congruence with the guidelines that sojourner family peace center has for individuals who qualify for their interview process. 2.3. data gathering the survey included 22 questions, ranging from yes/no to open-ended (appendix 1). the questions directly measured the opinion of the women and their encounters with the screening process for domestic violence, as well as the treatment for their symptoms in any emergency department visit. the women also provided their opinion on any improvements they believed could be made during their entire visit to an emergency department. the survey was conducted during the women’s initial visit to the center. the written survey was completed by the participant with the help (if needed) of a sojourner representative during their in-person interview process. our survey was placed within the interview sojourner conducts for their own purposes. it was presented to the woman interviewed as being part of one long question process. data gathering and interviews were done by dr. erin schubert, director of outcomes & evaluation at sojourner family peace center. dr. erin schubert is also currently the sojourner representative who completes each interview sojourner distributes. dr. schubert is trained in performing interviews, distributing surveys, and working with abuse victims. dr. erin schubert made it clear to the participants that, this survey was a voluntary research activity distinct from the rest of the standard interview. if the domestic violence survivor reported having been to an emergency department for abuse-related or non-abuse-related care since her last interview/survey completion, we conducted another survey. if she had not, then no survey was conducted. each of these interviews were independent of each other and any previous visit to the emergency department did not play a role in a subsequent visit. this follow up interview/survey was again anonymous. the interviews were conducted and recorded by erin schubert in a private room at sojourner. the surveys were then stored in a locked, limited access area, available to only dr. erin schubert and minimal sojourner representatives. the surveys were stored separately from any other forms or surveys sojourner distributes. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e68 3. results 24 surveys were collected over the course of 7 months. thirteen women presented to the ed for treatment of physical injuries related or not related to abuse. the remaining 11 denied ever presenting to an ed for treatment related to injuries from abuse. ten out of the thirteen (77%) women who completed surveys identified problems with the abuse-related care they received. for example, women were screened for domestic violence while a family member was present in the room with them. others were screened while law enforcement was present. most were screened by either a nurse, social worker, or police officer, not a physician. a handful of women felt as though they were being rushed by their healthcare professionals and that they did not genuinely care. however, the most noticeable complaint was that these women were not screened at all. eleven women were screened for domestic violence when they presented to the emergency department. of these eleven, seven were screened privately, three were screened with another family member present in the room with them, and 1 was screened with her husband, the abuser, in the room. amber recalled an encounter while her husband was in the room. the doctor just "asked me about my knee. i said i fell down." even if she had been able to speak about it, "i was totally unaware that anyone could have even helped me. i would have needed someone to clue me in." three out of the 13 women who presented to the emergency department stated they were not comfortable being around, or talking to people in law enforcement. they stated that they had negative attitudes about police, and that they felt that the police did not care about them or their safety. comments from brianna stated the following. "police = bad. didn’t care. didn’t believe me. took forever to get to the house then they didn’t even arrest him." "it wasn’t their fault (doctors/nurses) at all but keep that officer outta there." one woman in particular, chelsea, stated the following in regards to law enforcement: "i went there a few times. the nurse woman who was asking all the questions about my relationships so i could tell that they were suspicious and kind of know what was up. she just turned around her badge and was telling me how she dates a guy in the police and all that. she was very nice and open and all that. i just wasn’t going to open up to them. my ex-fiance was so smart and manipulative and was in law enforcement so who knows who he knew and what they were telling him" four women reported they either felt rushed while being screened or that the person screening them did not genuinely care. one also felt as though the provider screening them felt uncomfortable asking the questions. diana reported, "i did feel comfortable at first and told them all that until i realized they really didn’t care and weren’t believing so then i was just like okay whatever." another comment from eva stated, "i would’ve felt safer if they took their time and didn’t rush. i mean i understand they got other patients and all that, but it just takes a minute to ask." francesca recalls, "they did ask a lot of questions. it seemed like they were sometimes trying to avoid the subject or avoid crossing the line or something." during an encounter giovanna remembers, "they just sent me on my way like they don’t care at all about it." out of the 13 women who presented to the ed with symptoms related to domestic violence; four were not screened. this included heidi who reported the following: "i was pistol whipped and had a split open head. no one there asked me about dv." as well as ingrid who stated, "i had a sprained ankle and sprained wrist from a domestic violence incident. when i went in, i just said i fell down the stairs doing laundry." jennifer also recalled, "my husband and i were fighting and he bit my finger, so i went in. just asking me instead of brushing it off. i mean i had a human bite on me. . . like duh!" two women stated they were not given any community resources to contact following their stay in the emergency department and they felt as though if they would have had received resources it would have been extraordinarily helpful and maybe they would not have had to go back to an abusive home after discharge. and finally, kalie stated the following: "maybe if they could provide some sort of housing information or funds so i didn’t feel like i had to go back to home.’ 4. discussion from this data collection, we have started to gain valuable insight on the interactions between healthcare personnel and victims of domestic violence in the emergency department. the most valuable information is that there is still the possibility of women presenting with obvious symptoms of abuse, such as a human bite wound or head injury, not being screened. presenting to an emergency department with a head injury or human bite wound should warrant screening of domestic violence. another important piece of information we have gathered is that when screening is done, it is often not completed in a private or secure manner. the majority of screening is being done by either a nurse, social worker, or law enforcement. it is rarely being done by physicians. while the sample size gathered may be small, the 13 survivors surveyed represent a significant portion of women who have experienced domestic violence and have beneficial insight to help improve care and treatment in the emergency department. even with the relatively small samthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rodriguez et al. 4 ple size, it is evident that screening for domestic violence is dire and needs to occur more often than what is currently happening. our research shows the importance of continuing research on domestic violence screening and what can be done to improve care in the emergency department. these courageous women who have shared their personal stories with us can help pave the way to better treatment for future victims of domestic violence who present to the emergency department hoping for care and safety. from this collaboration, we hope to gain information that will describe the ways emergency department personnel interact with domestic violence victims when providing care. this information will help us identify desirable behaviors of physicians and other professional care givers, as well as ways they can improve their behavior/attitude/treatment of domestic violence victims when they present to the emergency department. this data will help us understand what is working well and what needs improvement in regards to domestic violence victims in the emergency department. we hypothesize that there will be characteristics of the emergency department that are working well, but that there will also be areas that need improvement to provide the most beneficial care for domestic violent victims during their visit. we recommend universal screening of domestic violence to all women who present to emergency department. this screening must be done privately. it is extremely important to screen patients secluded from people who may influence their conversations and safety. there are multiple opportunities for healthcare professionals to pull their patients in a private room in order to make them feel safe enough to open up. if a family member or abuser is adamant about not leaving the patient’s side, then personnel can tell them they need the patient for an x-ray, blood draw, or sensitive exam in order to get the patient alone for an opportunity to screen them. domestic violence screening should always be done in a safe environment, private room, with no other family members or personnel with them. most victims of domestic violence do not feel comfortable interacting with law enforcement and removing them from the patient’s room could be the first step to making the women feel safe in the emergency department and possibly allow them to open up about their experiences. standardizing who screens patients for domestic violence may be a way to properly train healthcare personnel to adequately and respectfully screen. this could also help improve the way personnel ask the questions to hopefully make the domestic violence victim feel less rushed and more at ease. having an appointed person or advocate to screen for domestic violence will also ensure that every person who presents to the emergency department is screened. this advocate may then be able to stay with a woman who has confirmed she is a victim of domestic violence so she can feel safe throughout her entire stay in the emergency department. they can also present standardized community resources to ensure her safety following her discharge from the emergency department. 5. limitation limitations to this study include the small sample size. there was a relatively lower number of women who presented to sojourner family peace center for initial interviews during the time period of our data collection. 6. conclusion we gained valuable insight on interactions between healthcare personnel and dv victims. dv screening must be done with no family present. removing law enforcement from rooms is recommended to make women feel more comfortable. if a family member is adamant about remaining with the patient, the patient can be removed for a blood draw or sensitive exam to attain privacy. standardizing screening could aid in making dv victims feel less rushed and more at ease. the courageous women sharing personal stories help pave the way to better treatment for future victims of dv presenting to the ed. 7. appendix 7.1. acknowledgements we would like to acknowledge dr. stephen hargarten, associate dean, director, comprehensive injury center, professor of emergency medicine at the medical college of wisconsin, and dr. kevin hamberger, professor of family and community medicine, medical college of wisconsin for being our esteemed mentors and guiding us through the research and publication process. we would also like to acknowledge dr. erin schubert and sojourner family peace center for giving us the opportunity to collect this data in their walls and for being a safe haven for domestic violence victims. 7.2. author contribution management and analysis of data was done by brieana rodriguez and madalyn mandich, medical students at the medical college of wisconsin. the entire research project was overseen by dr. stephen hargarten, associate dean, director, comprehensive injury center, professor of emergency medicine at the medical college of wisconsin, and dr. kevin hamberger, professor of family and community medicine, medical college of wisconsin. authors orcids brieana rodriguez: 0000-0002-0436-8668 madalyn mandich: 0000-0002-4379-255x this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e68 7.3. funding/support no funding was used in this project. 7.4. conflict of interest there are no conflicts of interest that must be declared in regards to this study. references 1. rhodes kv, frankel rm, levinthal n, prenoveau e, bailey j, levinson w. "you’re not a victim of domestic violence, are you?" provider–patient communication about domestic violence. annals of internal medicine. 2007;147(9):620. 2. joint commission on accreditation of healthcare organizations ( jcaho) [cited 2019 27.10.2019]. available from: https://www.omnex.com/members/standards/jcaho/ jcaho.aspx. 3. acep. domestic family violence [updated april 2019]. available from: https://www.acep.org/patientcare/policy-statements/domestic-family-violence/. 4. moyer va. screening for intimate partner violence and abuse of elderly and vulnerable adults: us preventive services task force recommendation statement. annals of internal medicine. 2013;158(6):478-86. 5. larkin gl, hyman kb, mathias sr, d’amico f, macleod ba. universal screening for intimate partner violence in the emergency department: importance of patient and provider factors. annals of emergency medicine. 1999;33(6):669-75. 6. aspe. screening for domestic violence in health care settings aspe; 2013. available from: https://aspe.hhs.gov/report/screening-domesticviolence-health-care-settings. 7. violence nncad. the nation’s leading grassroots voice on domestic violence. available from: https://ncadv.org/. 8. center sfp. our mission. available from: https://familypeacecenter.org/about/our-mission/. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem b. rodriguez et al. 6 appendix 1: domestic violence screening questions 1. have you ever gone to an emergency room for treatment of physical injuries from abuse? yes— no— 2. have you ever gone to an emergency room for treatment of stress-related problems that are related to abuse (for example, headaches, stomach problems, insomnia, etc.)? yes— no— 3. have you ever gone to an emergency room for emotional support because of abuse? yes— no— 4. did anyone ask you questions about domestic violence? yes— no— if yes, did the provider ask the questions in such a way that showed they were interested in what you had to say? yes— no— 5. did you feel the physician really listened to you and believed you? yes— no— 6. did the hospital staff treat you with respect? yes— no— 7. did the hospital staff make you feel safe? yes— no— 8. were you asked these questions privately or was a partner, family member, etc. present? —privately —partner present —family present 9. who asked you the questions about domestic violence? —doctor —nurse —physician’s assistant —social worker—do not know what their role was 10. did the person asking you the screening questions about domestic violence make you feel more or less comfortable sharing your current situation? —comfortable —no opinion —uncomfortable 11. when they asked you about domestic violence, did they also ask about whether you had a head injury? yes— no— 12. when they asked you about domestic violence, did they also ask about whether you were choked or strangled? yes— no— 13. was your medical exam done in a way that made you feel respected? yes— no— 14. were you given any community resources to contact following your stay in the emergency department? (check all that apply) for example, domestic violence pamphlets, hotline numbers, etc. —pamphlet —hotline phone number —name and contact information for another agency —other if other, please list: 15. were you given any information about sojourner family peace center, milwaukee women’s center, community advocates, battered women’s shelter, or any other place you could go to after leaving the emergency department? —sojourner family peace center —milwaukee women’s center —community advocates —battered women’s shelter —other if other, please list: 16. do you feel that the health care providers in the emergency department were helpful? yes— no— open ended questions: 17. if comfortable, talk me through your emergency department visit. 18. on a scale from 1-10, how satisfied were you with your treatment while in the emergency department? 1 being highly unsatisfied and 10 being highly satisfied. 1 2 3 4 5 6 7 8 9 10 19. is there anything you would change on how you were treated in the emergency department by the health care providers? 20. is there anything that a doctor could have done/could do that would help you feel safe telling them about violence or abuse you have experienced? 21. do you have any other comments about how doctors have been helpful or harmful when you have been treated for abuse related injuries in the emergency department? 22. as a result of your experience(s) in the emergency department, did you make any changes to improve your safety? for example, develop a safety plan, change locks, get a restraining order, leave the relationship, connect with community resources, etc. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e59 or i g i n a l re s e a rc h piro, sofa and meds scores in predicting one-month mortality of sepsis patients; a diagnostic accuracy study ali vafaei1,2, kamran heydari1,2, seyed-saeed hashemi-nazari3, neda izadi4, hassan hassan zadeh1∗ 1. department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. 2. skull base research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 3. prevention of cardiovascular disease research center, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. 4. student research committee, department of epidemiology, school of public health and safety, shahid beheshti university of medical sciences, tehran, iran. received: june 2019; accepted: august 2019; published online: 20 october 2019 abstract: introduction: different scoring systems based on clinical and laboratory findings are designed for prediction of short-term mortality of patients with severe sepsis and septic shock. this study aimed to compare the screening performance characteristics of piro, sofa and meds scores in predicting one-month mortality of sepsis patients. methods: this diagnostic accuracy study was performed on septic shock and severe sepsis patients referring to emergency department of loghmane hakim hospital, tehran, iran, from 2017 to 2018. the performance of meds, sofa, and piro models in predicting 30-day mortality of patients was evaluated using discrimination and calibration indices. results: 200 patients with the mean age of 71.03±15.59 years were studied (61% male). during the 30 days, 66 patients died (mortality rate=33%). the area under the roc curve of piro, meds, and sofa scores were 0.83 (95% ci=0.78-0.89), 0.94 (95% ci=0.91-0.97) and 0.87 (95% ci=0.81-0.92), respectively. based on brier, brierscaled and nagelkerke’s r2 of the models, the best performance in predicting one-month mortality belonged to meds score. c-statistic showed that meds score had the highest value in the differentiation between the survived and non-survived cases. conclusion: this study showed that meds score performs better than piro and sofa scores in predicting one-month mortality of patients with severe sepsis and septic shock. keywords: decision support systems, clinical; patient outcome assessment; mortality; sepsis; shock, septic cite this article as: vafaei a, heydari k, hashemi-nazari s s, izadi n, hassan zadeh h. piro, sofa and meds scores in predicting one-month mortality of sepsis patients; a diagnostic accuracy study. arch acad emerg med. 2019; 7(1): e59. 1. introduction sepsis is the second common cause of mortality among patients in intensive care unit (icu), and it’s one of the top ten causes of death among all hospitalized patients (1). according to the centers for disease control and prevention (cdc) reports in united-states, at least 1.7 million people develop sepsis each year. also, approximately 270,000 americans die due to sepsis every year (2). based on world health organization (who) reports in 2018, burden of sepsis in low-andmiddle income countries is highest and sepsis, severe sepsis, ∗corresponding author: hassan hassan zadeh; department of emergency medicine, shahid beheshti university of medical sciences, tehran, iran. email: h.hassanzadeh88@yahoo.com, tel: 021-22915995 and septic shock lead to 20%, 40% and 60% of deaths per year, respectively (3, 4). nowadays, different scoring systems based on clinical and laboratory findings are applied for prediction of short term mortality in patients with critical situations (5, 6). these prediction tools can help the clinicians in selecting the best course of action for the treatment of critically ill patients to get better outcomes. sequential organ failure assessment (sofa), mortality in emergency department sepsis (meds), and predisposition, infection, response and organ dysfunction (piro) are three well-known tools for assessment of ill patients with sepsis, severe sepsis and septic shock (7, 8). sofa is an objective and simple scoring system that considers the number and severity of failures in six organs including respiratory system, coagulative function, liver, cardiovascular, kidney, and neurology system. this score ranges from 0 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. vafaei et al. 2 to 24 and higher points predict higher mortality probability. the range of piro scoring is 0 to 13 (9). usually rate of respiratory system, bandemia, pulse rate, and temperature are being evaluated and finally for the organ dysfunction, alteration in the mental status, according to the glasgow coma scale (gcs), systolic blood pressure, platelet count, prolongation of prothrombin time and etc. are being considered (10). different studies have compared these scores for predicting mortality, but there is not a general consensus regarding the best and most accurate rule in this regard (11-13). macdonald et al. reported that piro model performed better than sofa score and similar to meds score for predicting mortality in ed patients with severe sepsis and septic shock (14). in addition, in nguyen’s study, piro performed equally well when compared with apache ii and surpassed meds in discriminating survivors from non-survivors (11). therefore, in this study, we are going to compare the performance measures of sofa, piro, and meds scoring models in predicting 30-day mortality of septic shock and severe sepsis patients. 2. methods 2.1. study design and setting in this diagnostic accuracy study, septic shock and severe sepsis patients referring to loghmane hakim educational hospital in tehran province of iran from 2017 to 2018 were examined. the performance of meds, sofa, and piro models for predicting 30-day mortality were evaluated using discrimination and calibration indices. the protocol of study was approved by ethics committee of shahid beheshti university of medical sciences (ethics code: ir.sbmu.msp.rec.1396.119). the researched adhered to the principals of helsinki recommendations regarding the ethical consideration in medical researches. 2.2. participants all patients aged > 18 years with septic shock and severe sepsis who were admitted to intensive care unit (icu) during the study period were examined. patients with heart attack, pulmonary embolism, cancer, human immunodeficiency virus (hiv ) infection, trauma and those who had recent major surgery were excluded. the instructions of scores regarding the included patients’ characteristics were considered during data collection. 2.3. data gathering the necessary information from the clinical examination and medical records were extracted. data collection form included age, sex, admission ward, duration of admission, transfer type (ems or private car), history of smoking, opium abuse, history of different underlying diseases (kidney, hypertension, ischemic heart disease, icu hospitalization in previous 3 months, iv antibiotic therapy in previous 30 days, previous trauma), early and final diagnosis, and vital sign findings including tachycardia, tachypnea, temperature, blood pressure, respiratory rate. every patient was followed for at least one month (30 days). in absent cases, the research staff contacted the patient or patient’s family at certain intervals and attempted to collect the necessary medical information of the patient’s latest condition. a third year emergency medicine resident was responsible for data gathering, follow up, and calculation of scores for all patients, under the direct supervision of an emergency medicine specialist. 2.4. definitions severe sepsis was defined as having two or more criteria from the "systemic inflammatory response syndrome (sirs)", at least one criterion from signs of circulatory shock and one criterion from the evidence of infection (15). septic shock patients were those diagnosed with systolic blood pressure (sbp) lower than 90 mmhg who did not respond to treatment with at least one liter of crystalloid serum, and still had sbp<90 mmhg or lactate level ≥4 mmol. 2.5. sequential organ failure assessment (sofa) this score is used during the stay in the icu and is based on six different indices including: respiration (pao2/fio2 (mmhg) or sao2/fio2 (mmhg)), cardiovascular system (status of hypotension), liver function (bilirubin level (mg/dl) [µmol/l]), coagulation status (platelets count), kidney function (creatinine level or urine output) and neurology status (glasgow coma scale). sofa score ranges from 0 to 24 points and higher scores predict higher mortality probability in infected patients (16). 2.6. mortality in emergency department sepsis (meds) meds score comprises of nine variables, including terminal illness (6 points), septic shock, tachypnea or hypoxemia, platelet count<150,000 cells/mm3, bands>5%, age>65 yrs. (3 points for each variable, respectively), lower respiratory infection, nursing home resident, and altered mental status (2 points for each variable, respectively). in this study we used all these variables except bandemia for calculating meds score because bandemia was not reported for the patient in the hospital. hence the range of this score is from 0 to 24 points depending on whether variables were present or absent (17). 2.7. predisposition, infection, response, and organ dysfunction (piro) for calculation of piro score we used the first table provided by h. bryant et al, in their article (11). in this scoring system this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e59 patients got a score between 0 to 13 according to their age, co-existence of comorbidities like chronic liver disease, congestive cardiomyopathy, existence of community acquired urinary tract infection (uti) or hospital acquired uti and also the type of culprit pathogen, presence of tachycardia and tachypnea, and the number of organ failures and also hepatic failure (18). 2.8. statistical analysis for quantitative variables with non-normal distribution (evaluated using the kolmogorov-smirnov test) median (interquartile range=iqr) and for qualitative variables, count (percentage) were used to describe them. the distribution of age, weight, bmi, piro, meds and sofa scores among alive and died subjects were compared using t-test and mannwhitney test. in addition, the frequency of qualitative variables in the two groups was compared using chi-square and fisher’s exact test. we used univariate logistic regression to evaluate the association between meds, sofa and piro scores and 30-day mortality among the studied patients. the performance of meds, sofa, and piro models for predicting 30-day mortality were evaluated using discrimination and calibration indices. we calculated brier, brierscaled and nagelkerke’s r2 indices for overall performance, c-statistic, discrimination slope, validity indices (sensitivity, specificity, positive predictive value (ppv ), negative predictive value (npv ), positive likelihood ratio (plr) and negative likelihood ratio (nlr)), area under the curve (auc) and also box plots calculated for discrimination and calibration-in-the-large, calibration slope and hosmer-lemeshow tests were measured for evaluation of calibration. also, we calculated optimism corrected with the bootstrap method (500) for all performance indices. data were analyzed using the r software (version 3.4.1). in this study, p<0.05 was considered statistically significant for all statistical tests; yet, we presented the exact p values for all tests. 3. results 3.1. baseline characteristics of studied patients 200 patients with the mean age of 71.03 ± 15.59 (21 95) years were studied (61% male). during the 30-day follow up period, 66 (33.0%) patients died (mortality rate = 33.0%; all cases were admitted to icu). table 1 compares the baseline characteristics of studied patients between survived and nonsurvived groups. while the mean age was significantly higher in subjects who died, mean weight and bmi did not show any significant difference between the two groups. mean piro, meds and sofa scores were significantly higher in non-survived cases. although variables such as the history of underlying diseases were different in the two groups, most of the variables related to admission and vital signs in dead and alive groups were not significantly different. there was a significant association between piro, meds, and sofa scores with mortality (p<0.001). the odds ratio of piro, meds, and sofa scores in predicting the risk of one-month mortality were 1.9 (95% ci: 1.57 2.3), 2.14 (95% ci: 1.73 2.65), and 2.1 (95% ci: 1.71 2.59), respectively. 3.2. score performance measurements table 2 summarizes the overall performance, discrimination, and calibration of the scores in predicting the one-month mortality. 3.3. overall performance based on brier, brierscaled and nagelkerke’s r2 of the models, the best overall performance in predicting one-month mortality belonged to meds score. 3.4. discrimination c-statistic showed that the meds score had the highest value in the differentiation between the survived and dead people. based on box plots for predicted probabilities of death in meds, sofa and piro scores, the highest discrimination slope belonged to meds score (0.62) (figure 1). 3.5. calibration area under the roc curve of piro, meds, and sofa scores were 0.83 (95% ci=0.78-0.89), 0.94 (95% ci=0.91-0.97) and 0.87 (95% ci=0.81-0.92), respectively (figure 2). the optimal cut-off points were 11.5, 5.5 and 6.5 for meds, sofa and piro scores, respectively. at the cut point of 11.5, meds score had a sensitivity of 83.3% (95% ci: 72.1-91.4), specificity of 91.8% (95% ci: 85.8-95.8), ppv of 83.3% (95% ci: 73.0 91.4), npv of 91.8 (95% ci: 85.395.8), plr of 10.15 (95% ci: 5.7-18.1) and nlr of 0.18 (95% ci: 0.1-0.31). at the cut point of 5.5, sofa score had a sensitivity of 75.8% (95% ci: 63.6-85.5), specificity of 84.3% (95% ci: 77.0-90.0), ppv of 70.4% (95% ci: 59.7-81.7), npv of 87.6 (95% ci: 79.892.2), plr of 4.83 (95% ci: 3.18-7.32), and nlr of 0.28 (95% ci: 0.18-0.44). at the cut point of 6.5, piro score had a sensitivity of 77.3% (95% ci: 65.3-86.7), specificity of 72.4% (95% ci: 64.0-79.7), ppv of 57.9% (95% ci: 48.3-72.5), the npv of 86.6 (95% ci: 78.2-90.6), plr of 2.8 (95% ci: 2.1-3.8), and nlr of 0.31 (95% ci: 0.19-0.49). the agreement between predicted mortality using piro, meds, and sofa scores and the actual mortality of the study population was determined using hosmer-lemeshow (h-l) test. h-l was non-significant for all three scores (table 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. vafaei et al. 4 figure 1: box plots of predicted probabilities of death in meds, sofa and piro scores. the discrimination slope is calculated as the difference between the mean predicted probability of alive and died subjects (solid dots indicate means). figure 2: the area under the receiver operator characteristic (roc) curves of piro, meds, and sofa scores in predicting one-month mortality of severe sepsis and septic shock patients. piro = predisposition insult response and organ; meds = mortality in emergency department sepsis; sofa = sequential organ failure assessment. 4. discussion the results of the present study showed that meds scoring system has better discrimination and performance compared to the other two scoring systems in predicting 30-day mortality of septic shock and severe sepsis patients (area under the curve 0.94). on the best cut-off point, (score=11.5), specificity and sensitivity of this score were 91.8% and 83.3%, respectively. results of the present article are in accordance with the auc of 0.78-0.81 found in previous studies among patients with sepsis (8, 12, 14, 19). in addition, our results are in contrast with a recent study of emergency department sepsis patients (20), which found that meds score had an auc of 0.61 and another study (11) that found an auc of 0.63 for meds in a registry database of patients in the emergency department. differences in the results of various studies could be due to differences in the methods of study. a systematic review of scoring systems in the emergency department showed that there are considerable variation between studies in the mortality rates and inconsistency in the definition of sepsis, severe sepsis, and septic shock. these variations can make valid comparisons problematic (21). the concept of meds score is similar to piro and sofa scores, except that it is specifically designed for emergency patients. in meds score calculation, organ dysfunctions receives greater score. in addition to these organ dysfunction parameters, constant data such as age, rapidly terminal comorbid illness, presence of a lower respiratory infection and nursing home residence, is considered in meds score (8). therefore, meds score has higher clinical importance (22). however, this scoring system has some limitations, for example, some data required for meds score calculation such as the presence of lower respiratory infection and the number of platelets is not available at the time of triage management. an additional limitation is that in meds score calculation, subjective assessment of short-term mortality by the in-charge clinician has a large weighting (14). the present study showed that a cut off of more than 11.5 points for meds score effectively stratified septic shock and severe sepsis patients into two groups, which were significantly different in mortality rate. this cut off point was close to the cutoff point that chen et al. had calculated in their study (23). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e59 table 1: comparing the baseline characteristics of studied patients between survived and non-survived groups variable survived (n = 134) died (n = 66) p-value* demographics gender (male) 87 (71.31) 35 (28.69) 0.10 age (year) 66.02 (15.75) 81.18 (8.98) <0.001 weight (kg) 68.7 (11.48) 65 (10.32) 0.02 bmi (kg/m2 ) 23.85 (3.28) 23.05 (3.4) 0.10 icu admission no 98 (73.13) 36 (26.87) 0.009 yes 36 (54.55) 30 (45.45) duration of admission (day) <5 31 (54.39) 26 (45.61) 5-10 50 (70.42) 21 (29.58) 0.052 >10 53 (73.61) 19 (26.39) history living in a nursing home 9 (47.37) 10 (52.63) 0.07 smoking 41 (69.49) 18 (30.51) 0.62 cardiovascular failure 8 (44.44) 10 (55.56) 0.03 previous trauma 12 (57.14) 9 (42.86) 0.31 kidney diseases 20 (68.97) 9 (31.03) <0.001 end stage disease 68 (57.63) 50 (42.37) 0.001 hypertension 89 (63.57) 51 (36.43) 0.11 ischemic heart disease 26 (50) 26 (50) 0.002 icu admission (3 month ago) 43 (64.18) 24 (35.82) 0.54 serum lactate level <2 64 (92.75) 5 (7.25) <0.001 2-2.9 45 (86.54) 7 (13.46) 3-3.9 6 (60.00) 4 (40.00) ≥4 19 (27.54) 50 (72.46) drug history steroids 11 (61.11) 7 (38.89) 0.57 beta blocker 34 (51.52) 32 (48.48) 0.001 opium 25 (69.44) 11 (30.56) 0.73 iv antibiotic (> 30 days ago) 47 (54.65) 39 (45.35) 0.001 vital signs / sirs tachycardia 107 (63.69) 61 (36.31) 0.02 tachypnea 93 (64.58) 51 (35.42) 0.24 temperature (>38 or <35.5) 110 (65.87) 57 (43.13) 0.44 sbp<90 mmhg or map<70 17 (27.42) 45 (72.58) <0.001 wbc (>15000 or <4000) 84 (62.69) 50 (37.31) 0.06 respiratory rate > 20 95 (62.91) 56 (37.09) 0.03 acidosis 89 (64.03) 50 (35.97) 0.17 platelet < 150000 38 (56.72) 29 (43.28) 0.02 septic shock 21 (29.58) 50 (70.42) < 0.001 data are presented based of mean ± standard deviation or frequency (%).bmi=body mass index; icu: intensive care unit; iv: intravenous; sirs: systemic inflammatory response syndrome; sbp: systolic blood pressure; map: mean arterial pressure; wbc: white blood cell count. in present study, piro and sofa scores also showed high values of discrimination in predicting 30-day mortality in septic shock and severe sepsis patients (area under the curve 0.835 and 0.872 respectively). however, the discrimination value of these two scorings system was less than meds. other studies have evaluated the prognostic value of piro and sofa scoring systems in patients with sepsis (13, 23, 24). in chen’s study, piro model had an auc of 0.82 for 28-day mortality (23). in the de groot’s study, among low-risk sepsis patients, piro scoring system had an auc of 0.83; but in higher risk patients, it had an auc of 0.68 (24). one of the reasons for the lower prognostic value of piro and sofa scoring systems is that, piro model does not require knowledge of the infecting organism and has been adapted specifically for use in the emergency department (25). in this study, we used univariate models to evaluate prognostic values of these three indices. it is recommended to evaluate their performance in multivariate models and also externally validate these models in larger studies. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. vafaei et al. 6 table 2: comparing the baseline characteristics of studied patients between survived and non-survived groups (continue) variables survived (n = 134) died (n = 66) p-value* scores piro 5.08 ± 2.18 8.01 ± 1.9 <0.001* meds 8 (7 10) 16 (13 17) <0.001** sofa 3 (3 5) 7 (6 9) <0.001** source of infection urosepsis 35 (66.04) 18 (33.96) 0.86 wound sepsis 15 (83.33) 3 (16.67) 0.12 pneumosepsis 35 (49.3) 36 (50.7) <0.001 others 49 (84.48) 9 (15.52) 0.001 peripheral blood smear gram negative 42 (61.76) 26 (38.24) 0.25 gram positive 15 (57.69) 11 (42.31) 0.27 transfer type own car 57 (69.51) 25 (30.49) 0.52 ems 77 (65.25) 41 (34.75) data are presented as mean ± standard deviation, median (q1 q3) and frequency (%); piro: predisposition insult response and organ; meds: mortality in emergency department sepsis; sofa: sequential organ failure assessment. *based on t-test; ** based on mann-whitney test. table 3: performance characteristics of piro, meds, and sofa scores in predicting 30-day mortality of sepsis patients characteristics piro piro* meds meds* sofa sofa* overall brier 0.153 0.156 0.086 0.089 0.128 0.132 brierscaled (%) 30 30 61 61 41 41 r2 (nagelkerke)(%) 41 40.9 71.5 70.9 50 49.3 discrimination c-statistic 0.835 0.836 0.941 94 0.872 0.872 slope 0.31 0.62 0.42 calibration inthe-large 0 0.07 0 0.01 0 -0.01 slope 1 1 1 0.98 1 0.99 h-l tests, x2 (p) 2.92(0.93) 4.82(0.77) 7.03(0.53) h-l=hosmer-lemeshow; *optimism corrected with bootstrap method. 5. limitation our study has some limitations. firstly, this was a monocenter study. secondly the endpoint was defined as death in 30 days, but the death might have occurred for reasons other than sepsis; and finally, we just compared the performance of these three scores in univariate models. it is recommended to compare these three scores in multivariate prediction models controlling for other patients’ variables to obtain better prediction models for predicting short term mortality. 6. conclusion this work shows that meds score had an acceptable accuracy in predicting 30-day mortality of patients with severe sepsis and septic shock. 7. appendix 7.1. acknowledgements the authors would like to thank the clinical research development unit (crdu) of loghmane hakim hospital, shahid beheshti university of medical sciences, tehran, iran for their support, cooperation and assistance throughout the period of study. 7.2. author contribution a. v: contribution to study concept and design, acquisition, analysis and interpretation of data, drafting of manuscript k. h: contribution to study concept and design, acquisition, analysis and interpretation of data, drafting of manuscript ss. hn: contribution to analysis and interpretation of data, drafting of manuscript n. i: contribution to drafting of manuscript this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e59 hh. z: contribution to study concept and design, acquisition, analysis and interpretation of data, drafting of manuscript authors orcids ali vafaei: 0000-0002-7129-6457 kamran heydari: 0000-0001-8538-4645 hassan hassan zadeh: 0000-00017251-2548 7.3. funding/support there is no funding. 7.4. conflict of interest the authors declare that there is no conflict or interest. references 1. martin gs, mannino dm, eaton s, moss m. the epidemiology of sepsis in the united states from 1979 through 2000. n engl j med. 2003;348(16):1546-54. 2. rivara fp. introduction: the scientific basis for injury control. epidemiologic reviews. 2003;25:20-3. 3. mehrdad r, seifmanesh s, chavoshi f, aminian o, izadi n. epidemiology of occupational accidents in iran based on social security organization database. iranian red crescent medical journal. 2014;16(1):e10359. 4. brun-buisson c. the epidemiology of the systemic inflammatory response. intensive care med. 2000;26 suppl 1:s64-74. 5. fine mj, auble te, yealy dm, hanusa bh, weissfeld la, singer de, et al. a prediction rule to identify low-risk patients with community-acquired pneumonia. n engl j med. 1997;336(4):243-50. 6. lim ws, van der eerden mm, laing r, boersma wg, karalus n, town gi, et al. defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. thorax. 2003;58(5):377-82. 7. vincent jl, de mendonca a, cantraine f, moreno r, takala j, suter pm, et al. use of the sofa score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. working group on "sepsis-related problems" of the european society of intensive care medicine. critical care medicine. 1998;26(11):1793-800. 8. shapiro ni, wolfe re, moore rb, smith e, burdick e, bates dw. mortality in emergency department sepsis (meds) score: a prospectively derived and validated clinical prediction rule. critical care medicine. 2003;31(3):670-5. 9. marshall jc. the piro (predisposition, insult, response, organ dysfunction) model: toward a staging system for acute illness. virulence. 2014;5(1):27-35. 10. rathour s, kumar s, hadda v, bhalla a, sharma n, varma s. piro concept: staging of sepsis. journal of postgraduate medicine. 2015;61(4):235-42. 11. nguyen hb, van ginkel c, batech m, banta j, corbett sw. comparison of predisposition, insult/infection, response, and organ dysfunction, acute physiology and chronic health evaluation ii, and mortality in emergency department sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. journal of critical care. 2012;27(4):362-9. 12. safari s, shojaee m, rahmati f, barartloo a, hahshemi b, forouzanfar mm, et al. accuracy of sofa score in prediction of 30-day outcome of critically ill patients. turkish journal of emergency medicine. 2016;16(4):146-50. 13. de groot b, lameijer j, de deckere er, vis a. the prognostic performance of the predisposition, infection, response and organ failure (piro) classification in high-risk and low-risk emergency department sepsis populations: comparison with clinical judgement and sepsis category. emergency medicine journal : emj. 2014;31(4):292-300. 14. macdonald sp, arendts g, fatovich dm, brown sg. comparison of piro, sofa, and meds scores for predicting mortality in emergency department patients with severe sepsis and septic shock. academic emergency medicine : official journal of the society for academic emergency medicine. 2014;21(11):1257-63. 15. bone rc, sibbald wj, sprung cl. the accp-sccm consensus conference on sepsis and organ failure. chest. 1992;101(6):1481-3. 16. jones ae, trzeciak s, kline ja. the sequential organ failure assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. critical care medicine. 2009;37(5):1649-54. 17. sankoff jd, goyal m, gaieski df, deitch k, davis cb, sabel al, et al. validation of the mortality in emergency department sepsis (meds) score in patients with the systemic inflammatory response syndrome (sirs). critical care medicine. 2008;36(2):421-6. 18. rubulotta f, marshall jc, ramsay g, nelson d, levy m, williams m. predisposition, insult/infection, response, and organ dysfunction: a new model for staging severe sepsis. critical care medicine. 2009;37(4):1329-35. 19. shojaee m, safari s, sabzghabaei a, alavi-moghaddam m, arhami dolatabadi a, kariman h, et al. pro-bnp versus meds score in determining the prognosis of sepsis patients; a diagnostic accuracy study. emergency (tehran, iran). 2018;6(1):e4-e. 20. jones ae, saak k, kline ja. performance of the mortality in emergency department sepsis score for predicting this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. vafaei et al. 8 hospital mortality among patients with severe sepsis and septic shock. am j emerg med. 2008;26(6):689-92. 21. calle p, cerro l, valencia j, jaimes f. usefulness of severity scores in patients with suspected infection in the emergency department: a systematic review. the journal of emergency medicine. 2012;42(4):379-91. 22. geier f, popp s, greve y, achterberg a, glockner e, ziegler r, et al. severity illness scoring systems for early identification and prediction of in-hospital mortality in patients with suspected sepsis presenting to the emergency department. wiener klinische wochenschrift. 2013;125(1718):508-15. 23. chen yx, li cs. risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (piro) scoring system in septic patients in the emergency department: a cohort study. critical care (london, england). 2014;18(2):r74. 24. de groot b, de deckere er, flameling r, sandel mh, vis a. performance of illness severity scores to guide disposition of emergency department patients with severe sepsis or septic shock. european journal of emergency medicine : official journal of the european society for emergency medicine. 2012;19(5):316-22. 25. howell md, talmor d, schuetz p, hunziker s, jones ae, shapiro ni. proof of principle: the predisposition, infection, response, organ failure sepsis staging system. critical care medicine. 2011;39(2):322-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e66 ca s e re p o rt transient global amnesia in a patient presenting with hypertensive emergency; a case report takafumi obara1, tsuyosi nojima1, hitoshi koga2, atsunori nakao1, hiromichi naito1∗ 1. department of emergency, critical care and disaster medicine, okayama university graduate school of medicine, dentistry and pharmaceutical sciences, okayama, japan. 2. department of emergency medicine, st. mary hospital, kurume, fukuoka, japan. received: june 2020; accepted: july 2020; published online: 28 july 2020 abstract: transient global amnesia (tga) is characterized by the abrupt onset of global amnesia, particularly anterograde amnesia. the pathophysiology of tga is poorly understood and it could be caused by various factors and be associated with various diseases. we report a 58-year-old man who presented to the local emergency room with tga lasting for several hours. the patient had complete anterograde amnesia without a past medical history of migraine or neurological findings. his systolic blood pressure on presentation was 220 mmhg, which was immediately treated with intravenous calcium ion influx inhibitor. other than global amnesia, there was no evidence of neurological disturbance. computed tomography and magnetic resonance imaging results were unremarkable. after treatment of his hypertension, his amnesia resolved within 12 hours. emergency department physicians may encounter tga. correct diagnosis of the condition depends on recognizing the disease. keywords: amnesia, transient global; memory disorders; htpertension; arterial pressure; hypertension; stroke; emergencies cite this article as: obara t, nojima t, koga h, nakao a, naito h. transient global amnesia in a patient presenting with hypertensive emergency; a case report. arch acad emerg med. 2020; 8(1): e66. 1. introduction transient global amnesia (tga) is characterized by the abrupt onset of global amnesia, particularly anterograde amnesia. it is usually a self-limiting condition and does not coincide with other neurological symptoms or signs. while various causes, such as migraine, focal ischemia, epilepsy, or metabolic aspects, have been proposed, the pathophysiology of tga has not been fully elucidated. tga is considered to be a result of multiple causes rather than a single mechanism (1). we treated the unique case of a patient with a typical history of tga associated with hypertensive emergencies. there have been only a few reports showing the relationship between hypertension and tga episodes (1-3). since tga presents very dramatically and is sometimes seen in the emergency department, emergency physicians must be fa∗corresponding author: hiromichi naito; okayama university graduate school of medicine, dentistry and pharmaceutical sciences, department of emergency, critical care, and disaster medicine. 2-5-1 shikata, okayama, japan 700-8558. email: naito.hiromichi@gmail.com, tel: +81-86-235-7426, fax: +81-86-235-7427 miliar with this condition. sharing our experience may help emergency physicians to successfully diagnose tga by recognizing its characteristic features and avoid unnecessary testing. 2. case presentation a 58-year-old man came to the emergency department with amnesia since 2 hours before admission. his past history included only hypertension and treatment with amlodipine (5 mg/day). additionally, he had no family psychiatric history. he had woken up normally and had breakfast as usual prior to the onset of his amnesia. his family members noticed his repetitive questioning regarding where he was and how he got there, indicating his inability to encode new memories ("how did i come here?"; "why i am here?"). on arrival, he was alert and calm. the patient presented no seizures, altered mental status, headache, or visual disturbances. his vital signs were as follows; body temperature 36.7◦c, blood pressure 220/118 mmhg, and heart rate 84 beats/minutes. physical examination was unremarkable. other than the recent memory disturbance, there were no abnormal neurological signs such as sensory disturbance or muscle weakthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem t. obara et al. 2 ness. all his higher cortical functions like reasoning, calculations, language, and abstract thinking were intact. on interview, he could not recall why he had come to the hospital; however, he clearly stated his name, his work history, and his address. the patient could identify his family members. his biochemical and hematological indices were within normal limits. intravenous nicardipine (2 mg) was administered and his systolic blood pressure (sbp) dropped to 140150 mmhg. brain computed tomography (ct) scan demonstrated no hemorrhage or space occupied by a brain lesion. magnetic resonance imaging (mri) showed the absence of any localizing signs. his memory impairment fully recovered within 24 hours after the onset of symptoms. however, he did not remember the episode, including admission to the hospital and undergoing several examinations. on the day after admission, since recovery of his memory function was confirmed by interview, the patient was discharged on foot. in the three months of follow-up, he has been well without further amnesia episodes. 3. discussion our case fully met the hodges and warlow tga diagnostic criteria (4), which include a capable observer witnessing the attack, no neurological symptoms during or after the attack, anterograde amnesia, no personal identity loss, no recent head injury, no history of seizures or active epilepsy, absence of epileptic features, and resolution of tga within 24 hours. our patient did not have any head injury or seizure episodes for at least 10 years. we ruled out electrolyte/metabolic abnormality based on normal biochemical test and arterial blood gas analysis results. the following differential diagnoses were identified for our patient: complex partial seizures, acute confusional state, transient ischemic attack (tia), transient epileptic amnesia (tea), psychogenic amnesia, toxic metabolic states, and migraine. tea is an indication of temporal lobe epilepsy, and patients will have multiple episodes of amnesia; symptoms commonly last for less than an hour or rapidly recur, which did not happen in our case. psychogenic amnesia is characterized by profound retrograde amnesia with personal identity loss but intact anterograde memory; these symptoms do not correspond to those of our patient. we ruled out tia, which manifests additional focal neurological deficits during an attack, as our patient had no motor or sensory loss. episodic memory dysfunction in tga presents transiently. in contrast, it may present acutely in concussion, sub-acutely in thiamine deficiency, or chronically in alzheimer’s disease. since the pathophysiology of tga is obscure, many hypotheses have been proposed. a number of precipitating factors are closely related to tga, including physical exercise, migraines, sexual intercourse, acute pain, emotional stress, cervical hyperextension, and coughing (5-7). our patient did not have this type of episode based on information obtained from family members and no factor other than increased blood pressure, can fully explain the occurrence of tga in our patient. plausible hypotheses for the pathogenesis of tga are migraine-like mechanism and cerebral hypoxic-ischemic insult. studies using neuroimaging technologies like single photon emission ct scan show impaired blood flow in the parahippocampus, hippocampus, and mediobasal temporal region in tga patients (7). similarly, diffusion-weighted mri has demonstrated metabolic stress and structural changes in patients with tga (8). it has been useful for confirming ischemic amnesia (9). assessment of internal jugular venous flow has shown blockage and resulting venous ischemia to hippocampal or bilateral diencephalic structures occurring due to valsalva maneuvers, which may contribute to tga development (7, 10). the rare incidence of microembolic signals in tga patients indicates that embolism plays no essential role in tga development (11). his anterograde memory rapidly and completely returned within 24 hours, but he was not able to remember the memory loss episode. like our patient, patients in previous studies have reported that their retrograde memory was slow to recover to normal. arterial hypertension is a prominent finding in patients with tga and may be an associated risk factor (12). nedelmann et al. demonstrated that 21 of 22 patients with tga (60% female, mean age 62.4 years) had high sbp (180.9/98.3 mmhg mean pressure three hours after symptom onset). moreover, systolic values above 200 mmhg were found in one-third of patients. these clinical observations may suggest that elevated blood pressure is a common factor in the early stage of this condition (3). 4. conclusion we encountered the unique case of a patient with a typical tga history associated with hypertensive emergencies. our report may help emergency physicians to successfully diagnose the condition by recognizing its characteristic features. 5. declarations 5.1. acknowledgements no funding supported this study. 5.2. consent consent was obtained from the participant in this study. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e66 5.3. other relationships all authors have declared that they have no other relationships or activities that could appear to have influenced the submitted work. 5.4. authors contribution all authors met the criteria for authorship contribution based on recommendations of international committee of medical journal editors. authors’ orcids takafumi obara: 0000-0001-5760-1980 tsuyosi nojima: 0000-0003-0768-0179 hitoshi koga: 0000-0002-2686-5905 atsunori nakao: 0000-0002-6818-2985 hiromichi naito: 0000-0002-7308-1716 5.5. funding none. references 1. arena je, rabinstein aa. transient global amnesia. mayo clin proc. 2015;90(2):264-72. 2. nakamizo t, tsuzuki i, koide t. transient global amnesia with reversible white matter lesions: a variant of posterior reversible encephalopathy syndrome? case rep neurol med. 2015;2015:541328. 3. nedelmann m, kaps m. elevated blood pressure as a prominent finding in patients with transient global amnesia. eur j neurol. 2007;14(7):e22. 4. hodges jr, warlow cp. syndromes of transient amnesia: towards a classification. a study of 153 cases. j neurol neurosurg psychiatry. 1990;53(10):834-43. 5. espiridion ed, gupta j, bshara a, danssaert z. transient global amnesia in a 60-year-old female with posttraumatic stress disorder. cureus. 2019;11(9):e5792. 6. yi m, sherzai az, ani c, shavlik d, ghamsary m, lazar e, et al. strong association between migraine and transient global amnesia: a national inpatient sample analysis. j neuropsychiatry clin neurosci. 2019;31(1):43-8. 7. sander k, sander d. new insights into transient global amnesia: recent imaging and clinical findings. lancet neurol. 2005;4(7):437-44. 8. bartsch t, deuschl g. transient global amnesia: functional anatomy and clinical implications. lancet neurol. 2010;9(2):205-14. 9. michel p, beaud v, eskandari a, maeder p, demonet jf, eskioglou e. ischemic amnesia: causes and outcome. stroke. 2017;48(8):2270-3. 10. winbeck k, etgen t, von einsiedel hg, rottinger m, sander d. dwi in transient global amnesia and tia: proposal for an ischaemic origin of tga. j neurol neurosurg psychiatry. 2005;76(3):438-41. 11. jovanovic zb, pavlovic am, vujisic tesic bp, pekmezovic tp, kostic boricic mv, cvitan ez, et al. comprehensive ultrasound assessment of the craniocervical circulation in transient global amnesia. j ultrasound med. 2018;37(2):479-86. 12. melo tp, ferro jm, ferro h. transient global amnesia. a case control study. brain. 1992;115 pt 1:261-70. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e73 or i g i n a l re s e a rc h usefulness of immature granulocytes to predict high coronary syntax score in acute coronary syndrome; a cross-sectional study cihan bedel1∗, mustafa korkut1, fatih aksoy2, görkem kuş3 1. department of emergency medicine, health science university antalya training and research hospital, antalya,turkey. 2. department of cardiology, suleyman demirel university faculty of medicine, isparta, turkey. 3. department of cardiology, health science university antalya training and research hospital, antalya,turkey. received: july 2020; accepted: august 2020; published online: 15 september 2020 abstract: introduction: immature granulocytes (ig) in peripheral blood indicate increased bone marrow activation and inflammation, and syntax score (ss) is an anatomical scoring system based on coronary angiogram. this study, aimed to evaluate the relationship between ig and ss, as a new inflammatory marker in patients with acute coronary syndrome (acs). methods: patients aged >18 years who were diagnosed with acs in the emergency department were included in this study, which was planned as a cross-sectional study. patients were divided into two groups of patients with high and low sss according to coronary angiography results. demographic and laboratory parameters were compared between the groups. results: our study consisted of 78 patients diagnosed with acs, who met the inclusion criteria. the average age of the study group was 59 years, and 67.9% of the patients were male. 21 patients (26.9%) had high sss and 57 patients (73.1%) had low sss. mean ig% was significantly higher in high ss group compared to low ss group (0.71±0.25 vs 0.44±0.21 mg/dl, p<0.001). ig% can present a high ss with 76.2% sensitivity and 75.4% specificity at a cut-off value of 0.7. conclusion: ig was significantly higher in acs patients with high sss. it seems that ig can be used as a parameter, which is quickly accessible and cheap, in order to predict high ss in acs patients in daily clinical practice. keywords: inflammation; acute coronary syndrome; granulocytes; percutaneous coronary intervention; emergency medicine; atherosclerosis cite this article as: bedel c, korkut m, aksoy f, kuş g. usefulness of immature granulocytes to predict high coronary syntax score in acute coronary syndrome; a cross-sectional study. arch acad emerg med. 2020; 8(1): e73. 1. introduction acute coronary syndrome (acs) is one of the main reasons for admission to the emergency department and hospitalization. acs is usually characterized by atherosclerotic plaque rupture and complete or incomplete thrombosis of the coronary arteries, which is one of the most significant causes of mortality and morbidity [1, 2]. many pathophysiological factors influence this atherosclerotic process, and inflammation is one of these factors. inflammation plays a significant role in initiating atherosclerosis and facilitating its progression ∗corresponding author: cihan bedel; health science university antalya training and research hospital, kazim karabekir street postal zip code: 07100, muratpaşa, antalya, turkey. tel: +905075641254, fax: +902422494487, email: cihanbedel@hotmail.com. [3]. inflammatory markers, such as white blood cell (wbc), creactive protein (crp), neutrophil-lymphocyte ratio (nlr), and platelet-lymphocyte ratio (plr), have been researched in the demonstration of poor condition in cardiovascular events [4, 5]. immature granulocyte (ig), a parameter that is not adequately known by many clinicians, reflects the fraction of immature granulocytes in the peripheral blood. this parameter can be easily and quickly measured in automated blood cell analyzers. it has been revealed to be useful in predicting the severity of many disease processes, such as bacterial infection, acute inflammatory diseases, tissue necrosis, and acute transplant rejection, in recent years [6, 7]. synergy between percutaneous coronary intervention with taxus and cardiac surgery (syntax) score (ss) is an anatomical scoring system based on coronary angiogram, which can help with evaluating the severity of coronary artery this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. bedel et al. 2 disease and making revascularization decisions [8]. previously, many studies have examined the relationship between wbc, crp, neutrophil-lymphocyte ratio (nlr), and plateletlymphocyte ratio (plr) and ss; however, there are no studies evaluating the relationship between ig and ss in the literature. therefore, this study aimed to evaluate the relationship between ig and ss, as a new inflammatory marker in patients with acs. 2. methods patients aged >18, who had presented to the emergency department with pain in the chest and been admitted to the department of cardiology with a diagnosis of acs (unstable angina pectoris/myocardial infarction without st-segment elevation (nstemi)/myocardial infarction with st-segment elevation (stemi)), were included in this study, which was planned as a prospective cross-sectional study and performed during the period between december 01, 2019, and february 01, 2020. the diagnosis of acs was defined as having electrocardiographic (ecg) change and/or increase of cardiac markers along with chest pain, which was assumed to be typical chest pain. in compliance with american college of cardiology and european society of cardiology (acc/esc) criteria, stemi was defined as st-segment elevation in ecg and increase in all the derivations by âl’ě0.1mv in two consecutive derivations. necessary approval was received from the clinical research ethics committee for the study (no: irb-2019-355). written informed consent was obtained from all the patients, who agreed to participate in the study. 2.1. participants exclusion criteria were determined as being <18 years old, being pregnant, having a myeloproliferative disease (it may change hematological parameters), malignancy, having trauma or surgery history within the past 1 week, arrhythmia causing hemodynamic instability, heart failure, inflammatory bowel disease, granulocyte-colony stimulating factor, and using immunosuppressive agents or steroids. 2.2. data gathering acs patients’ age, gender, history of hyperlipidemia, history of hypertension (ht), history of diabetes mellitus (dm), family history, drugs, systolic blood pressure (sbp), diastolic blood pressure (dbp), and heart rates (hr) (pulse/min) were recorded. the minimum sample size with a two-sided alpha value of 5%, a statistical power of 80% was estimated to be 50 patients. we planned to enrol a total of 80 patients, taking into account the 20% expected failure rate. 2.3. syntax score and angiographic analysis in the study, coronary angiography (cag) was carried out for all the patients using the judkins technique. in order to grade the stenosis of the coronary vessels, stenoses over 50% in vessels with a size of ≥1.5mm were taken into consideration. ss was prospectively calculated by two experienced cardiologists using an algorithm based on the diagnostic angiogram. the final score was calculated using individual lesion scores by analysts who were blind to operational data and clinical outcomes. items such as whether the stenosis was total, the level and the size of the stenosis, presence of collateral flow, presence of bifurcation or trifurcation lesion, severe folds, and severe calcification were evaluated [9, 10]. 2.4. blood samples venous blood samples of the patients were taken within the first hour of admission to the emergency department before the primary cag. in the samples taken during admission, wbc, neutrophil count, lymphocyte count, and ig% ig count (igc) were measured using an automated blood analysis system (coulterâő lh 780 hematologic analyzer, beckman coulter inc. brea, usa). absolute cell numbers were used in the analyses. crp, haemoglobin, glucose values, and cardiac troponin t levels, which were measured during the admission, were recorded. the levels of total cholesterol, high-density lipoprotein (hdl), low-density lipoprotein (ldl), and triglycerides were recorded during admission to the coronary intensive care. the left ventricular ejection fraction (lvef) of the patients was measured using vivid s5 (ge healthcare, inc. chicago, il, usa) device connected to 2-4 mhz transducer via simpson’s method according to the recommendations of the american society of echocardiography [11]. according to cag results, patients with high sss (>22) and patients with low sss (≤22) were separated into two groups, and all the parameters were compared. 2.5. statistical analysis statistical analyses were conducted using spss 21.0 package program (spss inc., chicago, il). continuous variables were expressed as mean ± standard deviation, and categorical variables were given as number and percentage. an independent t-test was used for comparing the distribution of the parameters with normal distribution, and the mann-whitney u test was applied for those that did not have a normal distribution. in categorical data, the evaluation was made using the chi-square test. logistic regression was conducted for factors associated with high ss. the optimum cut off value of ig in predicting high ss was assessed through receiver operating characteristic (roc) analysis. statistical significance was defined as a p-value less than 0.05. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e73 table 1: comparing the baseline characteristics of patients with high (> 22) and low (≤ 22) syntax score variables syntax score p high (n=21) low (n =57 ) age (years) mean ± sd 66.00 ± 16.67 57.57 ± 14.15 0.057 gender n (%) male 15 (68.2) 38 (66.6) 0.789 female 6 (31.8) 19 (33.4) underlying comorbidity yes 25.55 34.19 13.62 no 8.71 11.49 5.84 vital signs sbp, mm hg 131.57 ± 14.92 144.14 ± 27.01 0.071 dbp, mm hg 83.19 ± 8.04 91.47 ± 15.26 0.006 heart rate, beats/min 83.07 ± 15.26 84.33 ± 15.26 0.283 ejection fraction, % 45.95 ± 12.57 55.7 ± 12.93 0.002 syntax score 27.78 ± 4.79 7.38 ± 6.24 <0.001 previous history current smoker 12 (57.1) 29 (50.9) 0.799 hypertension 11 (52.4) 28 (49.1) 0.500 diabetes mellitus 7 (33.3) 22 (38.6) 0.794 dyslipidemia 9 (42.9) 21 (36.8) 0.409 history of cad 8 (38.1) 6 (10.5) 0.009 laboratory findings wbc count (×103 /mm3 ) 13.03 ± 3.05 10.68 ± 4.15 0.003 neutrophil, (×103 /mm3 ) 8.77 ± 2.84 6.84 ± 3.4 0.005 lymphocyte, (×103 /mm3 ) 3.67 ± 3.20 2.97 ± 2.41 0.318 nlr 4.09 ± 3.91 3.14 ± 2.71 0.367 plr 112.14 ± 59.08 120.51 ± 57.22 0.499 hemoglobin, mg/dl 13.89 ± 1.97 13.55 ± 1.97 0.355 glucose (mg/dl) 163.33 ± 71.52 140.36 ± 69.22 0.017 igc(×103 /mm3 ) 0.08 ± 0.06 0.07 ± 0.01 0.004 ig% 0.71 ± 0.25 0.44 ± 0.21 <0.001 crp (mg/dl) 35.37 ± 17.12 3.92 ± 0.54 0.021 troponin t (ng l) 502.00 ± 157.07 426.08 ± 157.74 0.012 lipid profiles (mg/dl) triglycerides 162.72 ± 92.30 212.33 ± 134.39 0.188 total cholesterol 211.27 ± 65.80 220.64 ± 56.83 0.304 high-density lipoprotein 44.00 ± 9.01 46.28 ± 10.97 0.354 low-density lipoprotein 135.50 ± 57.34 134.66 ± 45.95 0.650 previous medication n (%) ras blocker 2 (9.5) 5 (8.8) 0.611 ace-i 2 (9.5) 14 (24.6) 0.210 beta blocker 3 (14.3) 15 (26.3) 0.368 diuretic 4 (19) 9 (15.8) 0.740 calcium channel blocker 6 (28.6) 8 (14) 0.184 statin 10 (47.6) 22 (38.6) 0.605 antiaggregant 5 (23.8) 12 (21.1) 0.766 oral antidiabetic drug 4 (19) 16 (28.1) 0.562 mortality number (%) 3 (14.3) 0 (0) 0.017 data are presented as mean ± standard deviation or frequency (%). syntax score: synergy between percutaneous coronary intervention with taxus and cardiac surgery; sbp: systolic blood pressure; dbp: diastolic blood pressure; cad: coronary artery disease; wbc: white blood cell; nlr: neutrophil lymphocyte ratio; plr: platelet lymphocyte ratio; igc: immature granulocyte count; ig%: immature granulocyte percentage; crp: c-reactive protein; ras: renin–angiotensin system; ace-i: angiotensin converting enzyme inhibitor. 3. results our study consisted of 78 patients diagnosed with acs, who met the inclusion criteria. the average age of the study group was 59 ± 15.21 years, and 67.9% of the patients were male. 21 patients (26.9%) had high sss (>22) and 57 pathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. bedel et al. 4 table 2: comparing the baseline characteristics of patients with high (> 0.6) and low (≤ 0.6) immature granulocyte variables immature granulocyte p high (n=22) low (n =56 ) age (years) mean ± sd 61.13 ± 20.28 59.33 ± 12.92 0.807 gender n (%) male 15 (68.2) 38 (66.6) 0.601 female 6 (31.8) 19 (33.4) vital signs sbp, mm hg 129.45 ± 16.31 145.19 ± 26.37 0.07 dbp, mm hg 83.54 ± 9.18 91.48 ± 15.15 0.024 heart rate, beats/min 84.81 ± 18.21 82.85 ± 8.92 0.367 ejection fraction, % 50.90 ± 11.51 54.01 ± 10.51 0.234 syntax score 17.21 ± 14.80 10.97 ± 8.31 0.024 previous history current smoker 13 (59.1) 28 (50) 0.615 hypertension 10 (45.5) 29 (51.8) 0.802 diabetes mellitus 7 (31.8) 22 (39.3) 0.610 dyslipidemia 5 (22.7) 25 (44.6) 0.120 history of cad 5 (22.7) 9 (16.1) 0.522 laboratory findings wbc count (×103 /mm3 ) 12.88 ± 3.92 10.70 ± 3.90 0.032 neutrophil, (×103 /mm3 ) 9.26 ± 3.78 6.61 ± 2.87 0.003 lymphocyte, (×103 /mm3 ) 3.70 ± 0.82 2.97 ± 0.96 0.526 nlr 4.22 ± 4.11 3.06 ± 2.73 0.111 plr 112.78 ± 61.46 119.95 ± 56.66 0.560 hemoglobin, mg/dl 12.95 ± 2.25 13.89 ± 1.78 0.131 glucose (mg/dl) 114.38 ± 63.50 148.07 ± 73.39 0.556 crp (mg/dl) 24.71 ± 14.98 7.35 ± 3.01 0.693 troponin t (ng l) 519.66 ± 156.17 424.96 ± 160.55 0.011 lipid profiles (mg/dl) triglycerides 175.11 ± 107.80 208.35 ± 132.05 0.381 total cholesterol 189.22 ± 41.98 227.73 ± 60.65 0.012 high-density lipoprotein 42.38 ± 8.90 46.80 ± 10.84 0.011 low-density lipoprotein 118.77 ± 31.18 140.03 ± 52.11 0.08 previous medication n (%) ras blocker 2 (9.1) 5 (8.9) 0.561 ace-i 3 (13.6) 13 (23.2) 0.535 beta blocker 4 (18.2) 14 (25) 0.766 diuretic 4 (18.2) 9 (16.1) 1.000 calcium channel blocker 5 (22.7) 9 (16.1) 0.522 statin 6 (27.3) 26 (46.4) 0.135 antiaggregant 5 (22.7) 12 (21.4) 1.000 oral antidiabetic drug 2 (9.1) 18 (32.1) 0.45 mortality number (%) 3 (13.6) 0 (0) 0.02 data are presented as mean ± standard deviation (sd) or frequency (%). sbp: systolic blood pressure; dbp: diastolic blood pressure; syntax score: synergy between percutaneous coronary intervention with taxus and cardiac surgery; wbc: white blood cell; nlr: neutrophil lymphocyte ratio; plr: platelet lymphocyte ratio; igc: immature granulocyte count; cad: coronary artery disease; wbc: white blood cell; nlr: neutrophil lymphocyte ratio; plr: platelet lymphocyte ratio; igc: immature granulocyte count; ig%: immature granulocyte percentage; crp: c-reactive protein; ras: renin–angiotensin system; ace-i: angiotensin converting enzyme inhibitor. tients (73.1%) had low sss (≤22). there was no statistical difference between the groups in terms of age and gender (p>0.05). patients with high sss had significantly lower dbp and lvef (p=0.006, p=0.002, respectively). patients with high sss had significantly higher cad history comorbidity (p=0.009). mean wbc, neutrophil, glucose, igc, and crp and troponin t levels were significantly higher in patients with high sss. the mean ig% was significantly higher in the high syntax score group compared to the low syntax score group (0.71±0.25 vs 0.44±0.21mg/dl, p<0.001) (figure 1). bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e73 table 3: screening performance characteristics of immature granulocyte percentage in predicting the syntax (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score in 0.7 cut off point characters value (95% ci) characters value (95% ci) sensitivity 76.2 (67.21-84.67) npv 76.5 (69.15 – 82.59 specificity 75.4 (66.11-83.81) plr 3.17 ( 2.2 4.57) ppv 76 (68.74 82.02) nlr 0.31 (0.21 –0.45) data are presented as mean ± standard deviation (sd) or frequency (%). sbp: systolic blood pressure; dbp: diastolic blood pressure; confidence interval (ci). ppv: positive predictive value; npv: negative predictive value; plr: positive likelihood ratio; nlr: negative likelihood ratio. figure 1: comparison of immature granulocyte levels between low and high syntax score groups. figure 2: receiver operating characteristic (roc) curve of immature granulocyte percentage for predicting high syntax (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score (p < 0.001). sides, the percentage of mortality was significantly higher in those with high sss (p=0.017). the demographic data and laboratory results of the groups are compared in table 1. 22 (28.2%) patients had high ig% values (>0.6), and 56 (71.8%) patients had low ig% values (≤0.6). as seen in table 2, the prevalence of oral antidiabetic drug use was higher at high ig% values, and mean dbp, hdl, and ldl values of patients were found to be significantly lower. in the group with high ig% levels, higher sss were detected compared to the patients with low ig% values (17.21±14.80 vs. 10.97±8.31, p=0.024). additionally, in the analysis of the roc curve, ig% was shown to predict high sss with 76.2% (95% cl: 67.21 – 84.67) sensitivity, 75.4% (95% cl: 66.11 – 83.81) specificity, and area under the roc curve of 0.803 (95% ci: 0.699 0.908) at a cut-off value of 0.7 (table 3, figure 2). 4. discussion to the best of our knowledge, this is the first study in the literature evaluating the relationship between ig and ss in acs patients. the main findings of this study suggested that ss was independently correlated with ig%. ss is a scoring system used to evaluate the complexity and prevalence of coronary artery disease based on cag. it is commonly used by many physicians to specify the optimal cardiovascular treatment strategy [12, 13]. studies have shown that patients with high sss may have poorer cardiovascular outcomes, and the score may be an independent predictor for percutaneous interventions. moreover, highrisk patients can be identified using this scoring system, and appropriate treatment methods can be selected [14, 15]. inflammation is critically important for the initiation and progression of coronary atherosclerosis. inflammation affects many conditions, such as endothelial dysfunction, leukocyte recruitment, and platelet activation during the atherosclerosis process [16]. recently, it has been revealed that many inflammatory markers, such as crp, platelet/lymphocyte ratio (plr) and neutrophil/lymphocyte ratio (nlr), wbc, tnf-α, and cytokines can be independent risk factors for atherosclerosis. the increase in these inflammatory markers has been shown to correlate with the degree this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem c. bedel et al. 6 and severity of cad [14, 17]. these inflammatory markers have been evaluated as prognostic markers for many cardiovascular diseases, such as coronary artery ectasia, stable cad, and myocardial infarction [18, 19]. 840 patients, who underwent coronary angiography for cad evaluation, were included in a recent study by sahin et al. in this study, nlr was shown to be significantly associated with cad severity in patients with stemi, and they also reported that nlr is an independent marker for ss [2]. in a recent study by altun et al., troponin t and nlr were significantly associated with the angiographic severity of acs evaluated with ss [16]. in a study conducted by kundi et al., it was reported that the ratio of the monocyte count to hdl could be used as a parameter that would be quickly accessible and cheap in order to predict high ss and it may be used in daily practice as well [13]. in a study conducted by sivri et al. on 175 patients, the wbc/mean platelet volume ratio was shown to be correlated with increased ss, and thus, shortand longterm mortality [1]. ig in peripheral blood indicates increased bone marrow activation, and it can be easily measured in automated blood analyzers. it has been shown in studies that the presence of immature granulocytes in peripheral blood, which is not normally observed in healthy people, can indicate bone marrow activation and serious infection [20, 21]. recent studies suggest that ig is correlated with prevalent intravascular coagulation and mortality in critical patients with suspected sepsis [22]. park et al. reported that high ig values are a good diagnostic sign for severe sepsis and septic shock within the first 24 hours after admission to the intensive care unit [23]. mathews et al. discovered that the increase in ig% was significant in appendicitis complications in the pediatric age group and only compared it with an increased crp level and left shift [24]. in this study, we showed that patients with high ig levels had higher sss. besides, mortality was higher at high ig levels. 5. limitations the first limitation was that our study, although it was designed prospectively, was conducted with a small number of patients due to the covid-19 pandemic. furthermore, the mono-center design of our study increases bias. as another limitation, the fact that the decision on cag was not made by the same physicians may have influenced the results. additionally, the period from the emergence of the symptoms until hospital admission could not be assessed, which may affect the values of inflammatory markers. finally, since patients with a history of cabg were not included in the study, ss could not be confirmed in this population. 6. conclusion ig was significantly higher in acs patients with high syntax scores. it seems that ig can be used as a parameter, which is quickly accessible and cheap, in order to predict the high syntax score in acs patients in daily clinical practice. 7. declarations 7.1. acknowledgements the authors would like to thank md. asli bedel for helping in preparation of this paper. 7.2. author contribution all the authors have a substantial contribution in the study design, data interpretation and writing and reviewing the manuscript. authors orcids cihan bedel: 0000-0002-3823-2929 mustafa korkut: 0000-0003-1665-1601 fatih aksoy: 0000-0002-6480-4935 görkem kuş: 0000-0002-6058-5501 7.3. funding/support no funding and support was received for this study. 7.4. ethical approval ethics committee approval was received for this study. 7.5. conflict of interest the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. references 1. sivri, s., et al., usefulness of white blood cell count to mean platelet volume ratio in the prediction of syntax score in patients with non-st elevation myocardial infarction. pakistan journal of medical sciences, 2019. 35(3): p. 824. 2. åd̄ahin, d.y., et al., neutrophil to lymphocyte ratio is associated with the severity of coronary artery disease in patients with st-segment elevation myocardial infarction. angiology, 2013. 64(6): p. 423-429. 3. moriya, j., critical roles of inflammation in atherosclerosis. journal of cardiology, 2019. 73(1): p. 22-27. 4. sari, i., et al., relation of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio with coronary artery disease severity in patients undergoing coronary angiogthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e73 raphy. kardiologia polska (polish heart journal), 2015. 73(12): p. 1310-1316. 5. silvestre-roig, c., et al., neutrophils as regulators of cardiovascular inflammation. nature reviews cardiology, 2020: p. 1-14. 6. karon, b.s., et al., evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients. clinical biochemistry, 2017. 50(1617): p. 956-958. 7. lima, l.r., et al., automated immature granulocyte count in patients of the intensive care unit with suspected infection. jornal brasileiro de patologia e medicina laboratorial, 2019. 55(3): p. 267-280. 8. collet, c., et al., integration of non-invasive functional assessments with anatomical risk stratification in complex coronary artery disease: the non-invasive functional syntax score. cardiovascular diagnosis and therapy, 2017. 7(2): p. 151. 9. sianos, g., et al., the syntax score: an angiographic tool grading the complexity of coronary artery disease. eurointervention, 2005. 1(2): p. 219-27. 10. neumann, f.-j., et al., 2018 esc/eacts guidelines on myocardial revascularization. european heart journal, 2019. 40(2): p. 87-165. 11. schiller, n.b., et al., recommendations for quantitation of the left ventricle by two-dimensional echocardiography. journal of the american society of echocardiography, 1989. 2(5): p. 358-367. 12. cerit, l. and z. cerit, vitamin d deficiency is not associated with higher levels of syntax score. brazilian journal of cardiovascular surgery, 2019. 34(1): p. 57-61. 13. kundi, h., et al., association of monocyte/hdl-c ratio with syntax scores in patients with stable coronary artery disease. herz, 2016. 41(6): p. 523-529. 14. kurtul, s., et al., neutrophil to lymphocyte ratio predicts syntax score in patients with non-st segment elevation myocardial infarction. international heart journal, 2014: p. 14-175. 15. zuin, m., et al., correlation and prognostic role of neutrophil to lymphocyte ratio and syntax score in patients with acute myocardial infarction treated with percutaneous coronary intervention: a six-year experience. cardiovascular revascularization medicine, 2017. 18(8): p. 565-571. 16. altun, b., et al., the relationship between high-sensitive troponin t, neutrophil lymphocyte ratio and syntax score. scandinavian journal of clinical and laboratory investigation, 2014. 74(2): p. 108-115. 17. kurtul, a., et al., association of platelet-to-lymphocyte ratio with severity and complexity of coronary artery disease in patients with acute coronary syndromes. the american journal of cardiology, 2014. 114(7): p. 972-978. 18. sarli, b., et al., neutrophil-to-lymphocyte ratio is associated with severity of coronary artery ectasia. angiology, 2014. 65(2): p. 147-151. 19. zab, b., et al., usefulness of neutrophil to lymphocyte ratio in predicting short-and long-term mortality after non–st-elevation myocardial infarction. the american journal of cardiology, 2010. 106(4): p. 470-476. 20. park, j.h., et al., delta neutrophil index (dni) as a novel diagnostic and prognostic marker of infection: a systematic review and meta-analysis. inflammation research, 2017. 66(10): p. 863-870. 21. senthilnayagam, b., et al., automated measurement of immature granulocytes: performance characteristics and utility in routine clinical practice. pathology research international, 2012. 2012. 22. seok, y., et al., delta neutrophil index: a promising diagnostic and prognostic marker for sepsis. shock, 2012. 37(3): p. 242-246. 23. park, b.h., et al., delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. bmc infectious diseases, 2011. 11(1): p. 299. 24. mathews, e.k., et al., utility of immature granulocyte percentage in pediatric appendicitis. journal of surgical research, 2014. 190(1): p. 230-234. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e48 co m m e n ta ry prone position in management of covid-19 patients; a commentary parisa ghelichkhani1, maryam esmaeili2∗ 1. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. nursing and midwifery care research center, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. received: april 2020; accepted: april 2020; published online: 11 april 2020 abstract: sars-cov-2 virus causes a pneumonia that was identified through fever, dyspnea, and acute respiratory symptoms and named covid-19. this disease exacerbates in a number of patients and causes pulmonary edema, multi-organ failure, and acute respiratory distress syndrome (ards). prevalence of ards among covid-19 patients has been reported to be up to 17%. among the introduced treatment methods for management of ards patients, prone position can be used as an adjuvant therapy for improving ventilation in these patients. here we reviewed the literature regarding the role of prone position in management of covid-19 patients. keywords: covid-19; severe acute respiratory syndrome coronavirus 2; sars-cov-2; prone position; respiratory distress syndrome, adult; pandemics cite this article as: ghelichkhani p, esmaeili m. prone position in management of covid-19 patients; a commentary. arch acad emerg med. 2020; 8(1): e48. dear editor: in late 2019, a new virus was introduced to the world, which caused covid-19. the virus rapidly spread all over the world and led to a high rate of mortality and became a great challenge for the healthcare staff. sars-cov-2 virus causes a pneumonia that was identified through fever, dyspnea, and acute respiratory symptoms and named covid19. (1). this disease exacerbates in a number of patients and causes pulmonary edema, multi-organ failure, and acute respiratory distress syndrome (ards). prevalence of ards among covid-19 patients has been reported to be up to 17% (2). ards was first introduced in 1968 with clinical presentations such as acute hypoxemia, non-cardiac pulmonary edema, decrease in pulmonary compliance, and increase in work of breathing. it was especially seen in patients who had an underlying sepsis, pneumonia, and aspiration or severe trauma and all of these patients were in need of positive pressure ventilation (3). 10% of patients who are admitted to the intensive care unit (icu) develop ards (3) and despite all the treatment advances made, the rate of mortality is still high among these patients and has been reported to be between ∗corresponding author: maryam esmaeili; school of nursing and midwifery, tehran university of medical sciences, nosrat st., tohid sq.,tehran, iran. email: esmaeiliem@yahoo.com; tel: +982166937120, fax: +9821669042521 30% and 40% (3). among the introduced treatment methods for management of ards patients, prone position can be used as an adjuvant therapy for improving ventilation in these patients. it should be prescribed along with low tidal volume (6 cc per kg body weight) and infusion of neuromuscular blockers (cisatracurium for 48 hours). these 3 treatment strategies together, lead to improvement in oxygenation and survival of ards patients (4). the main mechanisms of prone position in improvement of ards patients’ condition are affecting recruitment in dorsal lung regions, increasing end-expiratory lung volume, increasing chest wall elastane, decreasing alveolar shunt, and improving tidal volume (5). patients remaining in lengthy prone position sessions leads to decrease in mortality of patients (6). however, correct selection of patients and applying the proper treatment protocol for prone positioning are key to its effectiveness. for instance, in a meta-analysis, munshi et al. expressed that prone position can lead to a drop in the rate of mortality among patients with severe ards when applied to patients for least 12 hours a day (7). additionally, in another meta-analysis it was revealed that prone position can only reduce mortality due to ards when patients are ventilated with low tidal volume, the treatment is started within the initial 48 hours of initiation of the disease, and patients have severe hypoxia. in other words, prone position this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. ghelichkhani & m. esmaeili 2 can reduce mortality only when prescribed for patients with severe impaired oxygenation, in the initial hours, and for long durations (8). recently, in a multi-centered observational study, guãl’rin et al. showed that only 13.7% of patients with ards have been placed in prone position. even in patients with severe ards, the rate of using this technique was 32.9%. in the mentioned study, 2 main reasons were given for the physicians’ reluctance to use this treatment method: 1based on the judgment of the physicians in most cases, the hypoxia in severe ards patients is not severe enough to justify using prone position. 2most ards patients have hemodynamic instability, which prevents the physicians from deciding to use prone position (9). in addition to the effectiveness of this treatment method, caretaking aspects and the side effects of this position on ards patients should also be considered. patients that undergo ventilation with ventilator in prone position face risks such as accidental removal of the tracheal tube, limited access to the venous route, bending or pulling of the catheters and chest tube, pressure wound, bruising around the mouth due to presence of the tracheal tube, edema around the eyes and facial edema, gastroesophageal reflux, hyper-salivation and skin injuries (10). in prone position, the patient should face the ventilator and in patients with tracheostomy, a roll of fabric or pillow should be placed under the shoulders to prevent airway obstruction, these patients should receive muscle and nerve relaxant medications and high-dose sedation as infusion, eye pads should be used for closing the patients’ eyes to prevent corneal ulcers. considering the condition of these patients and presence of pressure on their stomach, the probability of reflux after gavage is very high, so they must be closely monitored regarding aspiration of gastric contents (10). the position of patients placed in prone position should be changed every 2 hours and sides should be switched. at least 3 to 5 individuals should participate to correctly put intubated patients in prone position, which is a serious limitation for keeping the patient in this position for a long time. to solve this problem a tool called vollman has been introduced for facilitation of moving patients placed in this position to prevent pressure wounds and deformity of joints (11). overall, it seems that studies on the effectiveness of prone position in ards patients clearly point out that correct patient selection, timely initiation and duration of patient’s placement in this position can all affect the effectiveness of this treatment method. available meta-analyses show that prone position can decrease mortality in ards patients when performed in the initial hours of disease manifestation, in patients with severe impaired oxygenation and for a long time (8). the minimum suggested duration of prone position is 12 hours a day. 1. declarations 1.1. authors contributions all authors met the criteria for gaining authorship based on the recommendations of the international committee of medical journal editors. authors orcids parisa ghelichkhani: 0000-0003-3763-7999 maryam esmaeili: 0000-0002-4798-2270 1.2. funding support no fund has been received. 1.3. conflict of interest none. references 1. ammirati f, colivicchi f, santini m. diagnosing syncope in clinical practice. implementation of a simplified diagnostic algorithm in a multicentre prospective trial–the oesil 2 study (osservatorio epidemiologico della sincope nel lazio). european heart journal. 2000;21(11):935-40. 2. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. the lancet. 2020;395(10223):507-13. 3. matthay ma, zemans rl, zimmerman ga, arabi ym, beitler jr, mercat a, et al. acute respiratory distress syndrome. nature reviews disease primers. 2019;5(1):1-22. 4. piehl ma, brown rs. use of extreme position changes in acute respiratory failure. critical care medicine. 1976;4(1):13-4. 5. kallet rh. a comprehensive review of prone position in ards. respiratory care. 2015;60(11):1660-87. 6. guerin c, reignier j, richard j-c, beuret p, gacouin a, boulain t, et al. prone positioning in severe acute respiratory distress syndrome. new england journal of medicine. 2013;368(23):2159-68. 7. munshi l, del sorbo l, adhikari nkj, hodgson cl, wunsch h, meade mo, et al. prone position for acute respiratory distress syndrome. a systematic review and meta-analysis. annals of the american thoracic society. 2017;14(supplement_4):s280-s8. 8. mora-arteaga j, bernal-ramãŋrez o, rodrãŋguez s. the effects of prone position ventilation in patients with acute respiratory distress syndrome. a systematic review and metaanalysis. medicina intensiva (english edition). 2015;39(6):359-72. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e48 9. guerin c, beuret p, constantin jm, bellani g, garciaolivares p, roca o, et al. a prospective international observational prevalence study on prone positioning of ards patients: the apronet (ards prone position network) study. intensive care medicine. 2018;44(1):22-37. 10. mccormick j, blackwood b. nursing the ards patient in the prone position: the experience of qualified icu nurses. intensive and critical care nursing. 2001;17(6):331-40. 11. klein dg. prone positioning in patients with acute respiratory distress syndrome: the vollman prone positioner. critical care nurse. 1999;19(4):66-71. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem declarations references archives of academic emergency medicine. 2020; 8(1): e44 rev i ew art i c l e accuracy of urine kidney injury molecule-1 in predicting acute kidney injury in children; a systematic review and meta-analysis mojtaba fazel1,2, arash sarveazad3,4, kosar mohamed ali5, mahmoud yousefifard6∗, mostafa hosseini1,7 †, 1. pediatric chronic kidney disease research center, tehran university of medical sciences, tehran, iran. 2. department of pediatrics, valiasr hospital, imam khomeini medical complex, tehran university of medical sciences, tehran, iran. 3. colorectal research center, iran university of medical sciences, tehran, iran. 4. nursing care research center, iran university of medical sciences, tehran, iran. 5. college of medicine, university of sulaimani, sulaimani, iraq . 6. physiology research center, iran university of medical sciences, tehran, iran. 7. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: february 2020; accepted: march 2020; published online: 5 april 2020 abstract: introduction: there is considerable controversy on the accuracy of kidney injury molecule-1 (kim-1) in prediction of acute kidney injury (aki) in children. therefore, the present study intends to provide a systematic review and meta-analysis of the value of this biomarker in predicting aki in children. methods: an extensive search was performed on the medline, embase, scopus and web of science databases by the end of 2019. cohort and case-control studies on children were included. urinary kim-1 levels were compared between aki and nonaki groups. findings were reported as an overall standardized mean difference (smd) with a 95% confidence interval (ci). also, the overall area under the receiver operating characteristic (roc) curve (auc) of kim-1 in predicting aki in children was calculated. results: data from 13 articles were included. urinary kim-1 levels in children with stage 1 aki were higher than the non-aki group only when assessed within the first 12 hours after admission (smd = 0.95; 95% ci: 0.07 to 1.84; p = 0.034). however, urinary kim-1 levels in children with stage 2-3 aki were significantly higher than non-aki children (p <0.01) at all times. the auc of urinary kim-1 in predicting aki in children was 0.69 (95% ci: 0.62 to 0.77). conclusion: based on the available evidence, kim-1 seems to have moderate value in predicting aki in children. since previous meta-analyses have provided other urinary and serum biomarkers that have better discriminatory accuracy than kim-1, so it had better not to use kim-1 in predicting aki in children. keywords: acute kidney injury; renal insufficiency; havcr1 protein, human; hepatitis a virus cellular receptor 1. cite this article as: fazel m, sarveazad a, mohamed ali k, yousefifard m, hosseini m. accuracy of urine kidney injury molecule-1 in predicting acute kidney injury in children; a systematic review and meta-analysis. arch acad emerg mede. 2020; 8(1): e44. 1. introduction acute kidney injury (aki) is one of the major public health problems worldwide, with a high incidence and many new ∗corresponding author: mahmoud yousefifard, assistant professor of physiology, physiology research center, hemmat highway, tehran, iran. e-mail: yousefifard.m@iums.ac.ir † corresponding author: mostafa hosseini, department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: mhossein110@yahoo.com cases annually (1). there are many complications that can result from this condition, including metabolic acidosis, elevated blood potassium levels, uremia, and changes in fluid balance. long-term complications of aki also include cardiovascular disease, stroke, and heart failure. children with aki mainly die from cardiovascular diseases and infections (2). current research suggests that the use of preventive strategies and rapid diagnosis of aki can lead to a significant reduction in the burden of aki (3). prompt diagnosis and treatment of the disease will enable slowing down the progression of the disease and prevent it from causing lastthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 2 ing complications, such as chronic kidney failure. despite significant advances in medical knowledge, delayed identification of aki can occur in some cases, and this may lead to persistent damage (4-6). therefore, researchers are looking for diagnostic methods for early aki identification. in recent years, serum and urine biomarkers have been suggested as reliable methods for rapid diagnosis of renal diseases, they have been shown to have better prognostic value compared to other techniques (7-9). these factors include serum creatinine, cystatin c, neutrophil gelatinase-associated lipocalin (ngal) protein, and kidney injury molecule-1 (kim-1) (1012). kim-1 is a membrane protein, which is not detectable in serum/urine of healthy individuals. however, kim-1 is widely expressed in proximal tubule cells after ischemia and toxic conditions, and has been reported to be an appropriate marker in the diagnosis of aki (13, 14). systematic reviews and meta-analyses of adult studies suggest that urinary kim1 levels can be an appropriate marker for early detection of aki (14, 15). as can be seen, these meta-analyses were mainly performed on adults, while the number of studies on children has increased in recent years. in addition, there is considerable controversy on the accuracy of kim-1 in prediction of aki in children. therefore, the present study intends to provide a systematic review and meta-analysis of the value of this biomarker in predicting aki in children. 2. methods 2.1. study design this meta-analysis was designed based on the guidelines for meta-analysis of epidemiology statement, to evaluate the value of urinary kim-1 level in predicting aki in children (16). 2.2. search strategy to achieve the objectives of the present study, extensive searches were conducted on medline (via pubmed), embase, scopus, and web of science by the end of 2019. the search strategy was based on words related to kim-1 and aki. then, by combining these words with appropriate tags in the databases, searches were performed and relevant articles were screened. to find additional articles or unpublished data, manual search was performed in the bibliography of relevant studies as well as search in google and google scholar search engines. the search query used in medline database is reported in appendix 1. 2.3. selection criteria pico was defined as follows: p: paediatric patients with aki, i: urinary kim-1, c: compare with non-aki children, and outcome: discriminatory accuracy of kim-1. in the present study, cohort and case-control studies on the accuracy of kim-1 in predicting aki in children were included. studies were included if aki was confirmed by a standard procedure and urine samples were obtained from all participants. duplicate studies, review studies, studies without a non-aki group, and adult studies were excluded from the present study. 2.4. data extraction and risk of bias assessment the method of collecting and evaluating the data is described in detail in our previous meta-analyses (17-20). in summary, after searching and removing duplicates, two independent researchers reviewed the titles and abstracts of records and then full-texts of potentially eligible articles were assessed. disagreements were resolved in consultation with a third reviewer. the data collection checklist was designed based on the prisma statement guidelines (21). extracted data included first author’s name, year of publication, sample size, age and sex distribution of patients, patients’ setting, aki definition criteria, kim-1 level assay method, time interval between patient’s admission and kim-1 level assessment, the mean and standard deviation of urinary kim-1 level, area under the receiver operating characteristic curve (auc), and sensitivity and specificity of kim-1 in predicting aki in children. the risk of bias was assessed using the proposed guidelines in quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies (22). 2.5. statistical analysis data were recorded as mean and standard deviation, auc, sensitivity, and specificity of kim-1 in predicting aki in children. most studies reported median and interquartile range instead of mean and standard deviation. therefore, cochrane’s proposed method was used to estimate the mean and standard deviation (23). all analyses were performed in stata 14.0 statistical program and "metan" command was used. findings were presented as standardized mean difference (smd) with a 95% confidence interval (95% ci) to compare the mean urinary kim-1 level in aki group with non-aki group. since the time interval between admission and kim1 assessment varied between 0 and 96 hours in the included studies, analyses were performed in three time subgroups including 0-12 hours, 12-24 hours, and 24-96 hours. also, in the eligible studies, patients were divided into three groups based on aki severity, including stage 1 (or high-risk) aki, stages 2-3 (or injury and failure) and all severities (stages 13). for this reason, the analysis was also performed based on these subgroups. for this purpose, being high risk was considered as stage 1 aki, injury was deemed equivalent to stage 2 aki, and failure was deemed equivalent to stage 3 aki. an additional analysis was performed to pool the aucs reported for urinary kim-1 level in predicting aki in children. in this section, the aucs of urinary kim-1 with their 95% ci were recorded in the statistical program and an overall auc was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e44 reported. heterogeneity between studies was assessed using i2 test and p value less than 0.1 were considered significant (indicating heterogeneity). in addition, publication bias was assessed using the funnel plot (egger’s tests) (24). 3. results 3.1. characteristics of included studies a search of databases yielded 2011 non-duplicated studies. during screening, 29 articles were reviewed in detail, and finally the data of 13 articles were included in the present meta-analysis (25-37) (figure 1). there were 8 cohort and 5 case-control studies. the sample sizes ranged from 33 to 252 children. the total sample size was 1620 children (825 of whom were boys). identification of aki in 8 studies were based on kidney disease improvement global outcomes (kdigo) criteria, based on pediatric risk, injury, failure, and end-stage kidney disease (prifle) criteria in 4 studies and based on aki network definition in 1 study. the interval between admission of patients and assessment of urinary kim-1 levels ranged from 0 to 96 hours. all studies used the elisa method to check the urine level of kim-1 and all of them had frozen the specimens at -80 ◦c prior to examination. table 1 shows the characteristics of the included studies. 3.2. risk of bias and publication bias assessment the quality control of studies was performed based on quadas-2 criteria. since the design of 5 studies was casecontrol, patient selection was associated with bias in these 5 studies and therefore, they were marked as having high-risk of bias. in other cases, the risk of bias and applicability were low risk (table 2 and figure 2). the analysis also revealed no evidence of publication bias in the present study (p = 0.576) (figure 2). 3.3. comparison of mean urinary kim-1 levels in children with and without aki urinary kim-1 levels were significantly higher in children with aki compared to non-aki children, regardless of severity of aki. as figure 3 shows, the urinary level of kim-1 in children with all intensities of aki (stage 1-3) was higher than non-aki children during first 12 hours after admission (smd = 0.84; 95% ci: 0.35 to 1.33; p = 0.001), 24-12 hours (smd = 0.48; 95% ci: 0.14 to 0.82; p = 0.006) and between 96-24 hours (smd = 1.08; 95% ci: 0.14 to 2.02; p = 0.024). 3.4. comparison of mean urinary kim1 levels between stage 1 aki and non-aki patients the urinary level of kim-1 in children with stage 1 aki was higher than the non-aki group only when examined within the first 12 hours of admission (smd = 0.95; 95% ci: 0.07 to 1.84; p = 0.034). however, 12-24 hours (smd = -0.05; 95% ci: -0.62 to 0.51; p = 0.859) and 24-96 hours (smd = -0.45; 95% ci: -1.17 to 0.28; p = 0.226) after admission, there was no difference between stage 1 aki and non-aki groups (figure 4). 3.5. evaluation of mean urinary kim-1 levels in stage 2-3 of aki and non-aki patients urinary kim-1 level in children with stage 2-3 aki was significantly higher than non-aki children. as figure 5 shows, the urinary kim-1 level in children with stage 2-3 aki were higher than non-aki children within the first 12 hours (smd = 0.84; 95% ci: 0.35 to 1.33; p = 0.001), 24-12 hours (smd = 1.02; 95% ci: 0.31 to 1.73; p = 0.005) and 96-24 hours (smd = 0.75; 95% ci: 0.27 to 1.22; p = 0.002) after admission. 4. discrimination 4.1. the auc of urinary kim-1 level in diagnosis of pediatric aki in four studies, auc of urinary kim-1 was reported with a 95% ci (26, 28, 33, 37). pooled analysis showed that auc of urinary kim-1 in prediction of aki was 0.69 (95% ci: 0.62 to 0.77). 4.2. sensitivity and specificity of urinary kim-1 level in diagnosis of pediatric acute kidney injury in the beginning of the present study, it was decided to evaluate the discriminatory power of urinary kim-1 based on sensitivity, specificity and diagnostic odds ratio. to achieve this goal, we needed data of true positive, false positive, true negative and false negative. but such information was not reported in the studies. only three studies reported the sensitivity and specificity of urinary kim-1 level in prediction of aki. in the first study, carvalho et al. showed that the best cut-off point for kim-1 in predicting chemotherapy-induced aki was 6.2 ng / mg of creatinine. in this cut-off, urinary kim-1 had a sensitivity and specificity of 73.1% and 92.1%, respectively (26). another study by sarafidis et al. showed that based on the best cut-off point (cut-off = 569.8 pg / ml), kim-1 had a sensitivity and specificity of 40% and 86%, respectively (36). finally, westhoff et al. reported sensitivity and specificity of 54.5% and 96.5%, respectively, for kim-1; indicating that the best cut-off point for this urine biomarker was 2235 pg / ml (37). 5. discussion the findings of the present study showed that mean urinary kim-1 level in children with stage 2-3 aki was significantly higher than the non-aki group. it was also found that the level of this biomarker in stage 1 aki patients was only higher this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 4 than the non-aki group when assessed within the first 12 hours of admission. however, the auc of urinary kim-1 in prediction of aki was 0.69, which is in the poor to fair range. pooled analysis in the present study showed that the urinary level of kim-1 was significantly higher in children with aki compared to non-aki cases. however, with a closer look at the findings, we will find that the obtained smd is often below 1, which is in the poor to moderate effect size range. therefore, kim-1 may not be a good biomarker for the prediction of aki in children. in addition, the auc of this biomarker being poor to fair generally indicates that the discriminatory accuracy of kim-1 is moderate at best. several methods have been suggested for assessing the discriminatory power of a biomarker. although auc calculation is the most common method in this field, it should be kept in mind that this test is a primary test and we require additional assessment such as sensitivity and specificity. however, sensitivity and specificity of kim-1 were only reported in three studies. the sensitivity of kim-1 to predict aki in children was between 40% and 73.1% and its specificity was between 86% and 96.5%. this sensitivity and specificity were reported based on a wide range cut-off points. therefore, we could not pool the data in this section. however, it seems that urinary kim-1’s sensitivity to predict pediatric aki is poor to fair. other findings of the present study indicate the weakness of kim-1 in differentiating patients at risk of aki (stage 1 aki) from non-aki patients. it seems that the level of kim-1 in the urine would increase significantly only when the patient is in the advanced stages of the aki (injury or failure phase). this is a major limitation for kim-1 in predicting aki in children. in a systematic review with the aim of examining the value of kim-1 in diagnosis of aki in children and adults, wang et al. showed that the auc, sensitivity and specificity of kim-1 in prediction of aki after cardiac surgery were 0.71, 76% and 0.84%, respectively (15). although the findings of the study by wang et al. are in line with the findings of the present study, there are major differences between the two studies. first, wang et al.’s study pooled the findings of studies on adults and children; and second, out of the 15 included studies, only 3 were studies on children. therefore, the findings of the study by wang et al. could not be generalized to the pediatric community. along with kim-1, there are other biomarkers such as cystatin c and ngal that studies have cited as reliable indicators of aki. three previous meta-analyses showed that urinary and serum levels of cystatin c and ngal had good to excellent discriminatory accuracy in predicting aki. in the first study, nakhjavan-shahraki et al. showed that sensitivity and specificity of serum cystatin c in predicting aki in children were 85% and 61%, respectively. the auc of serum and urine cystatin c in predicting aki were 0.83 and 0.85, respectively (4). in the other two meta-analyses, izadi et al. showed that the serum level of ngal in predicting aki was 87% sensitive and 88% specific, and its urinary level had a sensitivity and specificity of 92% in predicting aki. the auc of serum and urinary ngal in aki prediction was 0.94 and 0.97, respectively (5, 6). therefore, it seems that the use of ngal and cystatin c biomarkers in predicting aki is superior to kim-1 in children. 6. limitations in the beginning of the present study, it was decided to calculate the overall sensitivity, specificity, and diagnostic odds ratio of kim-1 in predicting aki in children, but after searching and entering studies it became clear that such analysis was not possible. on the other hand, out of the 13 included studies, 5 were case-controls. in this type of design, the research team is aware of the existence of aki in patients from the beginning, and this may lead to some degree of bias. also, since a wide range of cut-off points were reported for kim-1 in the studies, we were unable to reach a unique cut-off point for urinary kim-1 in predicting aki in children. 7. conclusion based on available evidence, kim-1 appears to have a moderate value in predicting childhood aki. since previous metaanalyses have shown urinary and serum biomarkers that have better discriminatory accuracy than kim-1, it is better not to use urinary kim-1 in predicting aki in children. 8. declarations 8.1. acknowledgment we are grateful to dr. behnaz bazargani and prof. nematollah ataei for their valuable consultations 8.2. author contributions study design: mahmoud yousefifard, mostafa hosseini data gathering: mojtaba fazel, arash sarveazad, mahmoud yousefifard analysis and interpreting the results: mahmoud yousefifard, mostafa hosseini, kosar mohammad ali drafting the manuscript: mahmoud yousefifard critically revising the paper: all authors all authors approved the final version of the manuscript and are accountable for all aspects of the work. authors orcid mojtaba fazel: 0000-0003-0463-4257 arash sarveazad: 0000-0001-9273-1940 kosar mohammad ali: 0000-0001-5533-2924 mahmoud yousefifard: 0000-0001-5181-4985 mostafa hosseini: 0000-0002-1334-246x this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e44 8.3. funding this study was funded and supported by tehran university of medical sciences (tums); grant no. 95-04-184-33088. 8.4. conflict of interest there is no conflict of interest. references 1. coresh j, selvin e, stevens la, manzi j, kusek jw, eggers p, et al. prevalence of chronic kidney disease in the united states. jama. 2007;298(17):2038-47. 2. anavekar ns, mcmurray jj, velazquez ej, solomon sd, kober l, rouleau j-l, et al. relation between renal dysfunction and cardiovascular outcomes after 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evaluation of urinary kim-1, ngal, and il-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi. clin nephrol. 2016;86(2):62-9. 31. krawczeski cd, goldstein sl, woo jg, wang y, piyaphanee n, ma q, et al. temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. j am coll cardiol. 2011;58(22):2301-9. 32. lagos-arevalo p, palijan a, vertullo l, devarajan p, bennett mr, sabbisetti v, et al. cystatin c in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine? pediatr nephrol. 2015;30(4):665-76. 33. mccaffrey j, coupes b, chaloner c, webb nj, barber r, lennon r. towards a biomarker panel for the assessment of aki in children receiving intensive care. pediatr nephrol. 2015;30(10):1861-71. 34. parikh cr, thiessen-philbrook h, garg ax, kadiyala d, shlipak mg, koyner jl, et al. performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of aki after cardiac surgery. clin j am soc nephrol. 2013;8(7):1079-88. 35. peco-antic a, ivanisevic i, vulicevic i, kotur-stevuljevic j, ilic s, ivanisevic j, et al. biomarkers of acute kidney injury in pediatric cardiac surgery. clin biochem. 2013;46(1314):1244-51. 36. sarafidis k, tsepkentzi e, agakidou e, diamanti e, taparkou a, soubasi v, et al. serum and urine acute kidney injury biomarkers in asphyxiated neonates. pediatr nephrol. 2012;27(9):1575-82. 37. westhoff jh, fichtner a, waldherr s, pagonas n, seibert fs, babel n, et al. urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury. pediatr nephrol. 2016;31(12):2353-63. 9. appendix 1: search query in pubmed "acute kidney injury"[mh] or "renal insufficiency"[mh] or acute kidney injury[tiab] or kidney injuries, acute[tiab] or kidney injury, acute[tiab] or acute renal injury[tiab] or acute renal injuries[tiab] or renal injuries, acute[tiab] or renal injury, acute[tiab] or renal insufficiency, acute[tiab] or acute renal insufficiencies[tiab] or renal insufficiencies, acute[tiab] or acute renal insufficiency[tiab] or kidney insufficiency, acute[tiab] or acute kidney insufficiencies[tiab] or kidney insufficiencies, acute[tiab] or acute kidney insufficiency[tiab] or kidney failure, acute[tiab] or acute kidney failures[tiab] or kidney failures, acute[tiab] or acute renal failure[tiab] or acute renal failures[tiab] or renal failures, acute[tiab] or renal failure, acute[tiab] or acute kidney failure[tiab] or acute kidney tubule necrosis[tiab])) and ("hepatitis a virus cellular receptor 1"[mh] or cd365 antigen[tiab] or kidney injury molecule 1[tiab]) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e44 table 1: characteristics of the included studies author; year; country study type setting age sample size no. of boys aki definition timing (hrs) askenazi; 2012; usa case-control aki suspected neonates 33 17 aki network 0 to 96 carvalho pedrosa; 2015; brazil cohort chemotherapy induced aki <18 64 26 kdigo 24, 48, 72, 96 dong; 2017; usa case-control post-cardiopulmonary surgery aki <18 150 77 kdigo 2, 6, 12 du; 2010; usa cohort aki suspected 11.4 252 126 kdigo 0 gist; 2017; usa cohort post-cardiopulmonary surgery aki <1 94 63 kdigo 6 kandur; 2016; turkey case-control icu admitted aki 1 to 17 60 33 kdigo 24 krawczeski; 2011; usa case-control post-cardiopulmonary surgery aki <18 220 110 kdigo 0, 6, 12, 24 lagos-arevalo; 2014; canada cohort aki suspected < 18 160 58 kdigo 0 to 24 mccaffrey; 2015; uk cohort aki suspected <18 49 26 prifle criteria 0 parikh; 2013; usa cohort post-cardiopulmonary surgery aki <18 311 171 prifle criteria 6, 12, 24, 48, 72, 96 peco-antic; 2013; serbia cohort post-cardiopulmonary surgery aki 1.6 112 65 prifle criteria 2, 6, 24, 48 sarafidis; 2012; greece case-control asphyxia-associated aki neonates 35 21 kdigo 24, 72 westhoff; 2016; germany cohort aki suspected <10 80 32 prifle criteria 0 aki: acute kidney injury; kdigo: kidney disease improving global outcomes; prifle: pediatric risk, injury, failure, loss of kidney function, and end-stage kidney disease; timing: time interval between admission and kidney injury molecule-1 assessment. table 2: quality assessment of included studies based on quadas-2 recommendations author; year risk of bias applicability patient index test reference flow and patient index test reference selection standard timing selection standard askenazi; 2012 § © © © © © © carvalho pedrosa; 2015 © © § © © © © dong; 2017 § © © © © © © du; 2010 © © © © © © © gist; 2017 © © § © © © © kandur; 2016 § © © © © © © lagos-arevalo; 2014 © © © © © © © mccaffrey; 2015 © © © © © © © peco-antic; 2013 © © © © © © © sarafidis; 2012 § © © © © © © westhoff; 2016 © © © © © © © ©: low risk pf bias, §: high risk of bias this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 8 figure 1: flow diagram of screening and selection of eligible studies. aki: acute kidney injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e44 figure 2: risk of bias and publication bias assessment of the included studies. there is no evidence of publication bias (p = 0.576). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 10 figure 3: forest plot for standardized mean difference (smd) of urine kidney injury molecule-1 (kim-1) between acute kidney injury (aki) patients with all severities (stage 1/risk, stage 2/injury, and stage 3/failure) and non-aki patients at different time cut offs. the urinary level of kim-1 in aki-patients is higher than non-aki patients. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e44 figure 4: forest plot for standardized mean difference (smd) of urine kidney injury molecule-1 (kim-1) between acute kidney injury (aki) patients in stage 1/risk and non-aki patients at different time cut offs. the urinary level of kim-1 in aki-patients with a severity of stage 1/risk is slightly higher than non-aki patients only when assessed during the first 12-hours after admission. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. fazel et al. 12 figure 5: forest plot for standardized mean difference (smd) of urine kidney injury molecule-1 (kim-1) between acute kidney injury (aki) patients with stage 2-3/injury-failure severity and non-aki patients at different time cut offs. the urinary level of kim-1 in aki-patients with a severity of stage 2-3/risk is higher than non-aki patients in all assessed time points. ci: confidence interval. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2020; 8(1): e44 figure 6: area under the curve (auc) of kidney injury molecule-1 (kim-1) in diagnosis of acute kidney injury in children. the discriminatory power of kim-1 in detection of acute kidney injury is poor to fair (auc = 0.69; 95% confidence interval: 0.62 to 0.77). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discrimination discussion limitations conclusion declarations references appendix 1: search query in pubmed emergency. 2018; 6 (1): e45 ca s e re p o rt intravascular hemolysis following acute zinc phosphide poisoning; a case report zana ramezani1, asrin babahajian2, vahid yousefinejad2∗ 1. student research committee, kurdistan university of medical sciences, sanandaj, iran. 2. liver & digestive research center, kurdistan university of medical sciences, sanandaj, iran. received: june 2018; accepted: july 2018; published online: 21 july 2018 abstract: zinc phosphide (znp) is low-cost, accessible, and very effective as a rodenticide. it has been used for many human suicide poisonings around the world, including iran. nonspecific gastrointestinal symptoms and cardiotoxicity are the most serious complications of znp poisoning, which are associated with a high mortality rate. the aim of this paper was to report a poisoned patient that ingested znp with suicidal attempt and faced complications due to hemolysis. keywords: zinc phosphide; poisoning; jaundice; hemolysis © copyright (2018) shahid beheshti university of medical sciences cite this article as: ramezani1 z, babahajian a, yousefinejad v. intravascular hemolysis following acute zinc phosphide poisoning; a case report. emergency. 2018; 6 (1): e45. 1. introduction zinc phosphide (znp) is a metallophosphide, dark grey and crystalline compound that is commonly used as a rodenticide due to its low cost and ease of availability (1, 2). znp poisoning could happen accidentally or intentionally as means of suicidal or homicidal attempts (3). routes of entry into the body could be via ingestion, inhalation or through the skin. the most common clinical symptoms in poisoned cases include nausea, vomiting, abdominal pain, hypotension, metabolic acidosis, respiratory alkalosis and acute renal failure (4). moreover, in some cases, rare complications such as acute pancreatitis, pulmonary edema, transient hyperglycemia, transient leucopenia and intravascular hemolysis may be seen (5-9). in this case report, we report a 37year-old male patient who ingested znp in order to commit a suicide and faces complications due to hemolysis. 2. case report a 37-year-old man with no significant past medical history was admitted to emergency ward with a history of acute ingestion of 8 packs (about 40 grams) of a dark grey, crystalline ∗corresponding author: vahid yousefinejad; liver and digestive research center, tohid hospital, geriashan ave, sanandaj, iran. postal code: 6616812131 tel:+98-87-33249435 email: hooman56y@yahoo.com compound rodenticide in order to commit suicide. on admission, the patient was lethargic and had nausea, vomiting, abdominal pain and lacrimation with the following vital signs: blood pressure: 130/80 mmhg, pulse rate: 110 beat/minute, respiratory rate: 22 per minute, temperature: 37◦c and saturation of o2: 92% in room air. the general physical and neurological examination was not significant. supportive therapy was initiated and he underwent gastric lavage with %0.9 nacl solution and activated charcoal treatment. primary results of laboratory tests in emergency department are shown in table 1. full blood count, coagulation parameters, biochemistry, and urine analysis were in normal range and mild metabolic acidosis was reported in arterial blood gas (abg) analysis. his electrocardiogram (ecg) only revealed sinus tachycardia. with the impression of organophosphorus poisoning, treatment with 0.5 mg intravenous atropine every 5 minutes and 2 grams intravenous pralydoxim every 6 hours was started. after receiving care for three days, the sclera and skin of the patient became icteric and nausea and epigastria pain increased. in laboratory tests, hemoglobin and platelet had decreased with normal coagulation parameters (table 2). liver enzymes, serum bilirubin, creatine phosphokinase (cpk) and lactate dehydrogenase (ldh) had increased. we started infusion of fresh frozen plasma (ffp) with diagnosis of hemolysis and diffuse intravascular coagulation (dic). the patient underwent antioxidant therapy with n this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com z. ramezani et al. 2 table 1: laboratory data of the patient in emergency department laboratory parameters normal range results laboratory parameters normal range results bun (mg/dl) 5-20 17 platelet count (*103 /m3 ) 150-400 298 creatinine (mg/dl) 0.5-1.5 0.7 ptt (s) 25–36 s 29 serum na (meq/l) 135-145 143 pt (s) 11–13 s 14.7 serum k (meq/l) 3.5-4.5 3.5 inr 1-1.5 1.3 ldh (u/l) 225-500 273 bilirubin (mg/dl) cpk (u/l) 20-200 107 total 0.2–1.3 0.9 amylase (u/l) 30-100 66 direct < 0.2 0.2 blood glucose (mg/dl) 70-110 116 ast (iu/l) 11–47 38 wbc (*103 /m3 ) 4-11 9.6 alt (iu/l) 7–53 22 rbc (*103 /m3 ) 3.5-5.5 5.4 alp (iu/l) 38–126 50 hemoglobin (g/dl) 12.5-17.5 16.8 ph 7.35-7.45 7.33 bun: blood urea nitrogen; ldh: lactate dehydrogenase; cpk: creatinine phosphokinase; wbc: white blood cells; rbc: red blood cells; ptt: partial thromboplastin time; pt: prothrombin time; inr: international normalized ratio; ast: aspartate aminotransferase; alt: alanine aminotransferase; alp: alkaline phosphatase table 2: serial laboratory results of the patient during hospitalization laboratory parameters normal range 12 hours day 1 day 2 day 3 day 4 serum na 135-145 meq/l 136 140 138 135 138 serum k 3.5-4.5 meq/l 2.9 3.3 3 3.7 4 lactate dehydrogenase (ldh) 225-500 u/l 370 1325 2471 1840 768 creatinine phosphokinase (cpk) 20-200 u/l 450 625 706 400 68 white blood cells (wbc) 4-11 *103 /m3 6.4 10.1 18.4 10.2 6.6 red blood cells (rbc) 3.5-5.5 *106 /m3 3.8 2.44 3 3.5 4 hemoglobin 12.5-17.5 g/dl 12.3 7.6 9 10.5 11.8 platelet count 150-400 *103 /m3 209 129 151 168 252 partial thromboplastin time (ptt) 25–36 s 29 31 29 28 22 prothrombin time (pt) 11–13 s 14.7 20 16.1 12.7 12.4 international normalized ratio (inr) 1-1.5 1.3 3.9 1.3 1.5 1 total bilirubin 0.2–1.3 mg/dl 20 31.7 15.5 4.2 3.3 direct bilirubin </0.2 mg/dl 7.9 20 8.5 2.5 1.9 aspartate aminotransferase (ast) 11–47 iu/l 200 235 180 60 25 alanine aminotransferase (alt) 7–53 iu/l 190 163 131 82 70 alkaline phosphatase (alkp) 38–126 iu/l 572 656 429 409 372 ph 7.35-7.45 7.58 7.51 7.45 7.5 7.41 pco2 33-45 mmhg 32 37.9 38 36.2 35.3 hco3 22-28 meq/l 30.8 34.8 35.1 30.9 28.1 acetyl cysteine (nac) a dose of 150 mg/kg (9 gr) in 200cc dextrose-water (dw ) 5% injected in 15 minutes as loading dose, followed by 50 mg/kg (3 gr) in 500cc dw5% in 4 hours and then 100 mg/kg (6gr) in 1000cc dw5% in 16 hours as maintenance dose. in peripheral blood smear, we observed platelet aggregation and evidence of disseminated intravascular coagulation (dic). we transfused 2 units of pack cells due to hemoglobin level being 6.4 mg/dl and it reached 9 mg/dl thereafter. coagulation parameters also were corrected after infusion of ffp. on the ninth day of admission, the patient was stable, lab tests became normal and the patient was referred to psychiatry service and was discharged from toxicology service. 3. discussion phosphides (aluminum, calcium and zinc) have been used as rodenticides, but they have also been used for suicide attempts, especially in developing countries (10). a dosage of 4 to 5 grams of znp (55-70 mg/kg) could result in death due to acute toxicity in humans (3). the mechanism of action for znp is similar to aluminum phosphide as both produce toxic hydrogen phosphine (ph3) gas (4). when ingested, it is hydrolyzed by the gastric acid and transformed into phosphine gas, which mixes into the blood stream via the stomach and intestine vessels (3, 5). phosphine inhibits cytochrome c oxidase enzyme in the respiratory chain, which leads to widespread cellular hypoxia. the direct toxic effect of phosphine on the vessel wall produces bleeding diathesis, which may lead to hemorrhage in the gastrointestinal tract, eyes this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e45 and extremities (11). clinical symptoms are severe hypotension, myocarditis, pericarditis, acute pulmonary edema, gastrointestinal symptoms (nausea, vomiting and diarrhea), metabolic acidosis, congestive heart failure and acute kidney failure. moreover, retrosternal pain, shortness of breath, cyanosis, liver failure, severe hypoglycemia, delirium and tonic-colonic seizure may occur (12). currently, there is no known specific antidote for phosphine gas poisoning; so a high mortality rate (range 37 to 100%) is seen among people who are poisoned with it (5). the treatment for znp poisoning is supportive and symptomatic. there is a controversy regarding use of activated charcoal, but it is recommended to give a dose of it to the patient on admission as soon as possible (13). when standard conservative treatment fails, the only option to save the life of a znppoisioned patient with irreversible acute liver failure is liver transplantation (14). some reports have shown the benefits of using nac in patients with hepatic damage due to phosphine poisoning, so we treated our patient with nac (15). jaundice due to hepatic damage or intravascular hemolysis may also occur in organophosphorus toxicity (16, 17). in our patient, after 3 days of admission, jaundice started and developed due to intravascular hemolysis and acute hepatic failure as evident through indirect hyperbilirubinemia, elevated liver enzymes, reticulocytosis, hemolytic anemia, and the presence of schistocyte in peripheral blood smear. in some cases, hemolysis occurs due to g6pd deficiency but in our case, g6pd level was normal (18, 19). our patient had denied exposure to any other drug, including hemolytic agents, and had not received any such drug during his hospital stay. in one study, morphological changes in erythrocytes were reported following in vitro incubation with ph3 gas. however, all cells displayed crenation, and no hemolysis or heinz body formation was noted, thus it is unlikely that hemolysis can be related to the direct effect of ph3 on the red blood cells (20). our patient initially came to emergency ward with gastrointestinal symptoms (nausea and vomiting), decreased level of consciousness, and metabolic acidosis. we observed him and started conservative therapy. after 3 days, intravascular hemolysis and liver failure were initiated. we continued supportive care until his liver enzymes became normal and hemolysis was stopped. 4. conclusion: in patients poisoned with znp, jaundice may occur due to hepatic damage, but it can also result from intravascular hemolysis. 5. appendix 5.1. acknowledgements the authors would like to thank the emergency department staff of tohid hospital, sanandaj, iran. 5.2. authors contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest authors declare that they do not have any conflict of interest regarding the present manuscript. 5.4. funding none. references 1. bumbrah gs, krishan k, kanchan t, sharma m, sodhi gs. phosphide poisoning: a review of literature. forensic science international. 2012;214(1-3):1-6. 2. krieger r. handbook of pesticide toxicology, two-volume set: principles and agents: academic press; 2001. 3. zinc phosphide national library of medicine hsdb database 2017. available from: https://toxnet.nlm.nih.gov/cgibin/sis/search/a?dbs+hsdb:@term+@docno+1059. 4. proudfoot at. aluminium and zinc phosphide poisoning. clinical toxicology (philadelphia, pa). 2009;47(2):89-100. 5. sogut o, baysal z, ozdemir b. acute pulmonary edema and cardiac failure due to zinc phosphide ingestion. the journal of emergency medicine. 2011;40(6):e117-8. 6. sarma ps, narula j. acute pancreatitis due to zinc phosphide ingestion. postgraduate medical journal. 1996;72(846):237-8. 7. ostadi a, noshad h, ghaffari ar, banagozar a. transient leukopenia in zinc phosphide poisoning. journal of clinical research & governance. 2014;3(1):54-5. 8. jain j, jain vv, gupta op, jaikishen a. transient hyperglycemia in zinc phosphide poisoning. indian journal of endocrinology and metabolism. 2012;16(1):145-6. 9. arefi m, parsa av, yousefinejad v, darvishi n. intravascular hemolysis after aluminum phosphide poisoning. indian journal of forensic medicine & toxicology. 2013;7(1):240. 10. prabhu ma, agustinus r, shenthar j. suicidal zinc phosphide poisoning unmasking brugada syndrome and triggering near fatal ventricular arrhythmia. pacing and clinical electrophysiology : pace. 2016;39(2):198-201. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com z. ramezani et al. 4 11. aggarwal p, wali jp. diagnosis and management of common poisoning: oxford university press, usa; 1997. 12. dogan e, guzel a, ciftci t, aycan i, celik f, cetin b, et al. zinc phosphide poisoning. case reports in critical care. 2014;2014. 13. shannon mw, borron sw, burns m. haddad and winchester’s clinical management of poisoning and drug overdose. system. 2007;133:1. 14. saraf v, pande s, gopalakrishnan u, balakrishnan d, menon rn, sudheer ov, et al. acute liver failure due to zinc phosphide containing rodenticide poisoning: clinical features and prognostic indicators of need for liver transplantation. indian journal of gastroenterology : official journal of the indian society of gastroenterology. 2015;34(4):325-9. 15. oghabian z, afshar a, rahimi hr. hepatotoxicity due to zinc phosphide poisoning in two patients: role of nacetylcysteine. clinical case reports. 2016;4(8):768-72. 16. chittora m, meena s, gupta d, bhargava s. acute hepatic failure in aluminium phosphide poisoning. the journal of the association of physicians of india. 1994;42(11):924. 17. soltaninejad k, nelson ls, khodakarim n, dadvar z, shadnia s. unusual complication of aluminum phosphide poisoning: development of hemolysis and methemoglobinemia and its successful treatment. indian journal of critical care medicine: peer-reviewed, official publication of indian society of critical care medicine. 2011;15(2):117. 18. aggarwal p, handa r, wig n, biswas a, saxena r, wali jp. intravascular hemolysis in aluminium phosphide poisoning. the american journal of emergency medicine. 1999;17(5):488-9. 19. sood a, mahajan a, dua a. intravascular haemolysis after aluminium phosphide ingestion. journal of the royal society of medicine. 1997;90(1):47-8. 20. chin k, mai x, meaklim j, scollary g, leaver d. the interaction of phosphine with haemoglobin and erythrocytes. xenobiotica. 1992;22(5):599-607. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion conclusion: appendix references emergency. 2018; 6 (1): e22 le t t e r to ed i to r a simple device to control valsalva manoeuvre strain pressure; a letter to editor isabel fitzgerald1, andrew appelboam2∗ 1. university of exeter medical school, st lukes campus, heavitree rd, exeter, ex1 2lu, united kingdom. 2. emergency department, royal devon and exeter hospital, exeter, devon, united kingdom. received: february 2018; accepted: april 2018; published online: 10 april 2018 cite this article as: a simple device to control valsalva manoeuvre strain pressure; a letter to editor. emergency. 2018; 6(1): e22. dear editor: we read with interest the article by motamedi and colleagues about the use of a hand held manometer to measure strain pressure during valsalva manoeuvre (vm) treatment of supraventricular tachycardia (svt) (1). we also used a manometer in our study (revert) of a postural modification of the vm and are currently investigating the use of a simple, single patient use device to control vm strain pressure, nct number: nct03298880 (2, 3). such a device would be useful as blood pressure manometers are not always available and cannot be left with patients and other methods of generating the recommended strain such as syringes have been shown to be unreliable (4). we note that motamedi’s study demonstrated a cardioversion rate of 14.8% in supine participants, which was similar to the rate achieved in the revert trial by control participants in the semi recumbent position (17%) (2). in contrast, participants randomised to the modified vm in the revert trial, had a markedly improved cardioversion rate of 43% (2). this modification required participants to perform a 40 mmhg pressure strain for 15 seconds in a semi recumbent position but with supine repositioning and passive leg raise immediately after the valsalva strain. to our knowledge this is the first trial to study this modification and was not described in the “new modified version” quoted and referenced in motamedi’s paper. to achieve the best cardioversion rates, we recommend use of a modified vm as described above with the strain controlled by a manometer where possible. a simple, single patient use device designed to deliver the recommended pressure may be helpful to facilitate this in practice and could be kept by patients for future use (3). 1. appendix 1.1. acknowledgements not applicable. 1.2. author’s contribution isabel fitzgerald wrote and andrew appelboam edited the manuscript. 1.3. conflict of interest no conflict of interests. 1.4. funding and support not applicable. references 1. motamedi m, akbarzadeh ma, safari s, shahhoseini m. valsalva maneuver using a handmade device in supraventricular tachycardia reversion; a quasi experimental study. emergency. 2017;5(1):e81. 2. a appelboam ar, c mann, j gagg, p ewings, a barton et al. postural modification to the standard valsalva manoeuvre for emergency treatment of supraventricular tachycardias (revert): a randomised controlled trial: the lancet; 2015. 3. testing of a valsalva assis device (vad) in healthy volunteers performing a valsalva manoeuvre. clinicaltrialsgov2018. 4. thornton hs em, reynolds ja,coats tj. valsalva using a syringe: pressure and variation. . 2016;33. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com appendix references archives of academic emergency medicine. 2020; 8(1): e84 ca s e re p o rt splenic hematoma as a rare complication of colonoscopy; a case report maddalena zippi1∗, roberta pica1, ingrid febbraro2, francesco rocco pugliese3, francesca liguori3 1. unit of gastroenterology and digestive endoscopy, sandro pertini hospital, rome, italy. 2. unit of urgent digestive endoscopy, sandro pertini hospital, rome, italy. 3. emergency department, sandro pertini hospital, rome, italy. received: september 2020; accepted: september 2020; published online: 25 october 2020 abstract: splenic injuries after colonoscopy are an uncommon complication, which can lead to potentially unfortunate outcomes. their management depends on the type of the splenic damage (hematomas, lacerations, rupture). we describe the case of a woman who visited the emergency department due to abdominal pain and presyncopal condition, which had occurred 12 hours after she underwent a colonoscopy. an abdominal computed tomography scan showed a splenic hematoma and a hemoperitoneum. an emergency splenectomy was performed successfully. emergency physicians, who are at the forefront of diagnosing and treating patients, should consider this post-endoscopic complication in order to implement a prompt treatment. keywords: colonoscopy; computed tomography; hematoma; spleen; splenic rupture cite this article as: zippi m, pica r, febbraro i, pugliese fr, liguori f. splenic hematoma as a rare complication of colonoscopy; a case report. arch acad emerg med. 2020; 8(1): e84. 1. introduction splenic rupture is a rare complication that may occur following colonoscopy. the first description of this condition, due to an endoscopic procedure, dates back to 1974 (1). the main mechanisms involved are: tension of the splenocolic ligament and direct damage due to maneuvers of the colonoscope at the level of splenic flexure (2-4). the most likely predisposing causes are post-surgical adhesions, previous trauma, and underlying splenic pathology (2-4). hereby, we describe a rare case of a splenic rupture that occurred after lower endoscopy. 2. case presentation a 75-year-old woman was admitted to the emergency department due to abdominal pain associated to a presyncopal condition. twelve hours earlier, she had performed a complete colonoscopy as a post-polypectomy surveillance at another hospital. the patient reported an open∗corresponding author: maddalena zippi; unit of gastroenterology and digestive endoscopy, sandro pertini hospital, via dei monti tiburtini 385, 00157 rome, italy. email: maddyzip@yahoo.it, tel: +39-06-41433310, fax: +39-0641733847 cholecystectomy, denied any kind of trauma in the previous days and mentioned that she was suffering from hashimoto’s thyroiditis and arterial hypertension, for which she was regularly in treatment with levothyroxine sodium and calcium channel blocker. no anticoagulant/antiplatelet agents were taken. on admission, the oral temperature was 38.6◦c, blood pressure 105/55 mmhg, pulse rate was 98/minute and the respiratory rate 17/minute. increases in white blood cell count (16.4/mm3; neutrophils 85.1%) and plasma d-dimer 359 (nr: 2-200 ng/ml) associated with anemia (hemoglobin 10.7 g/dl) were present. renal, bilio-hepatic, and pancreatic functions were normal. physical examination revealed signs of peritoneal reaction to palpation. at this point, it was decided to perform an abdominal focused assessment with sonography (fast), which demonstrated a hemoperitoneum. a subsequent computed tomography (ct) with intravenous (iv ) contrast highlighted, in addition to the hemoperitoneum (yellow arrows), the presence of a hematoma due to the rupture of the spleen (white arrow), as shown in figure 1. abdominal ct scan revealed the presence of a splenic hematoma of about 11 cm (withe arrows) and a copious intra-abdominal hemoperitoneum with perihepatic fluid collection (yellow arrows), in both arterial (figure 1a) and portal phases (figure 1b). a diagnosis of grade iv splenic rupthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. zippi et al. 2 figure 1: abdominal computed tomography with intravenous contrast. ture was made, according to the aast (american association for the surgery of trauma) classification (5). the patient underwent an emergency laparotomy with splenectomy, recovered well, and was discharged ten days later in good condition. 3. discussion in a 2016 review, jehangir a et al. identified 172 cases of splenic rupture and noted an incidence of 1–21/100.000 for this complication, pointing out that it had a higher predominance among females (71.5% of cases), with a mean age of 63 years, and a previous history of abdominal surgery in 50.8–65% of cases (6). in a recent structured review, which included 45 articles for a total of 68 patients, ullah w et al. emphasized two very interesting points regarding this complication: 1) the main reasons for performing the colonoscopy were screening in 46% of cases and diagnostic in 28%; 2) complete splenic rupture was found in 22% of patients, whereas subcapsular hematoma, spleen laceration and spleen avulsion were present in 63% of them (7). as evidenced by the work of chow bl et al., its real incidence could be underestimated both due to the non-reporting of cases and the non-publication of the same (8). our patient, in addition to abdominal pain, manifested a presyncopal condition. in fact, hemodynamic instability was reported in 43.1% of patients known to be suffering from this disease (8). the diagnosis of a splenic rupture may be difficult, partly owing to the delayed onset of the symptoms, even partly because some physicians might not be aware of this rare complication. early identification of this event is critical, as mortality rate is around 5% (9). as already affirmed above, we hold the view that emergency doctors should take this endoscopic complication into account to make an early diagnosis and reduce the risk of mortality due to delayed treatment. early recognition of this condition and the subsequent prompt treatment are essential to improve the outcome of these patients. 4. conclusion splenic rupture may be a dangerous complication of colonoscopy. fast abdominal sonography performed in the emergency room certainly represents an excellent first diagnostic examination in suspected cases. nevertheless, abdominal ct scan represents the gold standard exam for detecting splenic rupture and splenectomy is required in most of cases. 5. declarations 5.1. acknowledgements the authors thank dr. saveria de vito, italian medicines agency, rome, italy, for english editing. 5.2. authors contribution (1) each author listed had contributed to the conception or design of the paper, or to the acquisition, analysis, or interpretation of data. (2) each author listed had participated in drafting the paper or revising it critically for important intellectual content. (3) each author listed gave final approval of the version to be published. (4) each author listed agreed to be accountable for all aspects of the paper, ensuring that questions related to the accuracy or integrity of any part are appropriately investigated and resolved. 5.3. conflict of interest no conflict of interest was declared by the authors. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e84 5.4. financial disclosure the authors declared that this study has received no financial support. references 1. wherry d. colonoscopy-fiberoptic endoscopic approach to the colon and polypectomy. med ann dist columbia. 1974;43:189-92. 2. telmos a, mittal v. splenic rupture following colonoscopy. jama. 1977;237(25):2718-. 3. patel dd, shih dc, terry sm. splenic trauma from colonoscopy: a case series. international journal of surgery case reports. 2020;71:30-3. 4. dziadkowiec kn, stawinski pm, radadiya d, katz a. left shoulder pain after routine colonoscopy: an unusual presentation of splenic laceration. cureus. 2020;12(4):e7755. 5. dziadkowiec kn, stawinski pm, radadiya d, katz a. left shoulder pain after routine colonoscopy: an unusual presentation of splenic laceration. cureus. 2020;12(4):e7755. 6. jehangir a, poudel dr, masand-rai a, donato a. a systematic review of splenic injuries during colonoscopies: evolving trends in presentation and management. international journal of surgery. 2016;33:55-9. 7. jehangir a, poudel dr, masand-rai a, donato a. a systematic review of splenic injuries during colonoscopies: evolving trends in presentation and management. international journal of surgery. 2016;33:55-9. 8. chow bl, zia k. postcolonoscopy splenic rupture: the under-reporting of an unpropitious phenomena? bmj case reports cp. 2019;12(9):e231047. 9. barbeiro s, atalaia-martins c, marcos p, nobre j, gonçalves c, aniceto c. splenic rupture as a complication of colonoscopy. ge-portuguese journal of gastroenterology. 2017;24(4):188-92. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e76 or i g i n a l re s e a rc h iq-cpr meter for chest compression monitoring during simulated cardiopulmonary resuscitation; a comparative study phatthranit phattharapornjaroen1, suwitchaya surapornpaiboon1, phanorn chalermdamrichai1, yuwares sittichanbuncha1, kittisak sawanyawisuth2∗ 1. department of emergency medicine, faculty of medicine ramathibodi hospital, mahidol university, bangkok, thailand. 2. department of medicine, faculty of medicine, sleep apnea research group, khon kaen university, khon kaen, thailand. received: august 2020; accepted: august 2020; published online: 19 september 2020 abstract: introduction: adequate chest compression is crucial for cardiopulmonary resuscitation (cpr). there are several chest compression monitoring devices with different costs. this study aimed to evaluate the agreement rate of improved quality of cardiopulmonary resuscitation meter (iq-cpr meter) and automated external defibrillator (aed) in chest compression quality monitoring. methods: in this comparative study, participants were instructed to perform chest compression on the cpr manikins with the set rate of 110 times/minute for two minutes. the cpr manikins had two monitors: aed (r series®, zoll company) and iq-cpr meter. aed showed the depth and speed of chest compression on the screen, while iq-cpr meter showed the depth of each chest compression by color light for quality of chest compression depth. video-based analysis was used to compare the chest compression quality monitoring between the 2 devices. results: there were 27 participants in the study with a mean age and body mass index (standard deviation; sd) of 26.00 (5.65) years, and 22.93 (3.62) kg/m2 (70.37% male). the median (1s t to 3r d quartile range) of chest compression experience was 3 (1.00-6.50) years. the mean (sd) of chest compression rate was 107 (5.29) times/minute. based on cohen’s kappa correlation, agreement between the iq-cpr meter and the aed was 66.54%. conclusion: the iq-cpr meter had fair agreement with the computerized chest compression monitoring device with lower cost and simple, real time audiovisual feedback. keywords: quality indicators, health care; heart arrest; cardiopulmonary resuscitation; simulation training cite this article as: phattharapornjaroen c, surapornpaiboon s, chalermdamrichai p, sittichanbuncha y, sawanyawisuth k. rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative studyiq-cpr meter for chest compression monitoring during simulated cardiopulmonary resuscitation; a comparative study. arch acad emerg med. 2020; 8(1): e76. 1. introduction cardiac arrest is a fatal condition affecting more than 290,000 adult patients each year in the united states (1). over 50% of cardiac arrests are caused by cardiac causes; with the survival rate of approximately 20%. chest compression is an important part of cardiopulmonary resuscitation (cpr) that should be delivered to the victim as soon as possible (2). the 2017 version of american heart association (aha) recommendations recommends chest compression-only cpr for lay res∗corresponding author: kittisak sawanyawisuth; 123 mitraparp road, department of medicine, faculty of medicine, khon kaen university, khon kaen, 40002, thailand. email: kittisak@kku.ac.th, tel: 66-43-363664, fax: 66-43348399 cuers trained in chest compression. the recommended chest compression: ventilation ratio is 30:2. since 81% of cardiac arrest patients had non-shockable rhythm at presentation (1), chest compression is very crucial. the 2015 version of aha recommendations recommended a chest compression rate between 100 and 120 times/minute with depth between 5 and 6 cm (3). to comply with these recommendations, the quality of chest compressions needed to be monitored. there are several devices to assist chest compression such as automated feedback or audiovisual feedback (4-6). the prototype defibrillator with feedback improved adequate chest compression depth from 24% to 53% as well as short term survival (5). however, some devices may have high prices, which may not be suitable for the resourcelimited health care facilities. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. phattharapornjaroen et al. 2 the improved quality of cardiopulmonary resuscitation meter (iq-cpr meter) is a low-cost device with the aim of improving the quality of cpr, particularly chest compression. this custom-made device produced by the authors, costs 83 usd and provides real time feedback for chest compression. the iq-cpr meter has three main components: adjustable patch, signal bell, and depth indicator (figure 1). the adjustable patch is placed on the chest of the victim to evaluate chest compression depth. the signal bell is set for 110 times/minute to lead constant and proper chest compression rate by a ding sound. the depth indicator shows realtime feedback for adequate chest compression depth: no light indicates shallow depth (< 5 cm), green light indicates good depth (5-6 cm), and red light indicates too much depth (> 6 cm). this study aimed to evaluate if the iq-cpr meter shows agreement with a costly chest compression monitoring device. 2. methods 2.1. study design and setting this comparative study was conducted between the newly invented iq-cpr meter and the standard cpr monitoring device. we conducted the study at department of emergency medicine, ramathibodi hospital, mahidol university, bangkok, thailand. the study period was between may 1st and september 30th, 2018. baseline characteristics and chest compression experiences of eligible patients were recorded. the study protocol was approved by the committee on human rights related to research involving human subjects, mahidol university (mura2561/86). the participants gave informed consent prior to participation in the study. 2.2. participants the inclusion criteria were being an adult aged between 18 and 60 years, being among the active medical personnel at the ed, and willing to participate in the study. those who were pregnant or had comorbid diseases, which could cause inability to perform chest compression, such as heart disease or anemia were excluded. there were four categories of medical personnel participating in the study: faculty members or residents of emergency department (ed), 5th/6th year medical students, paramedic students, and emergency medical services (ems) staff. 2.3. procedure we instructed the participants to perform chest compression on the cpr manikins with the set rate of 110 times/minute; for two minutes. the cpr manikins had two monitors: automated external defibrillator (aed) r series®, zoll company and iq-cpr meter (figures 1). aed showed the depth and speed of chest compression rate on the screen, while the iqcpr meter showed the depth of each chest compression by color light. if the chest compression had a depth less than 5 cm, 5-6 cm, and more than 6 cm, the lights of the iq-cpr showed no light, green, and red, respectively. the participants performed chest compression for two minutes with video recording by the sony hdr pj440. data from the aed and the iq-cpr, including rate, depth, and full recoil of chest compression for each participant were retrieved from the video. the main primary outcome was chest compression depth, while the secondary outcomes included chest compression rate, and full recoil of chest compression. the data from aed were used as the standard values: chest compression depth, chest compression rate, and full recoil of chest compression. data from the iq-cpr were compared with the standard values from the aed. chest compression depth of each participant was scored by two authors (pp and ss) watching the video. the interrater reliability was 95%. 2.4. statistical analysis due to no previous data on the correlation of the iq-cpr meter and the standard monitoring, we performed an example study on the correlation between both devices on depth of chest compression. the agreement rate between the 2 devices on chest compression for two minutes was 0.85. with an error (d) of 0.02, alpha of 0.05, and z (0.975) or 1.959964, the required sample size was 6,123 times of chest compression. the required sample size was 27 participants to perform chest compression for two minutes with the rate of 110 times/minute. descriptive statistics were used to report baseline characteristics and outcome of the participants. baseline characteristics were age, sex, experience of chest compression, and body mass index, while the outcome of chest compression was depth, rate, and full recoil of chest compression. data were presented as mean (standard deviation; sd) or median (1s t to 3r d quartile range) for numerical variables based on normal distribution pattern. for categorical data, number (percentage) was reported. the main primary outcome was good depth of chest compression: 56 cm depth. the correlation between good depth of chest compression reported by the aed and the iq-cpr meter was evaluated using cohen’s kappa coefficient. there were three levels of agreement based on cohen’s kappa coefficient: excellent agreement (> 0.75), intermediate to good agreement (0.40-0.75), and poor agreement (<0.40). a subgroup analysis of various baseline characteristics was performed using cohen’s kappa coefficient. sensitivity and specificity of each category of the iq-cpr meter were calculated. the statistical analyses were performed using stata software, version 10.1 (college station, texas, usa). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e76 table 1: cohen’s kappa coefficients for chest compression depth between aed and iq-cpr meter in various populations study population cohen’s kappa coefficient (95% ci) all patients 67.25% (66.02%-68.46%) male 65.63% (64.15%-67.08%) female 71.21% (68.98%-73.38%) ep/residents 71.20% (68.84%-73.48%) medical students, clinical years 63.15% (60.62%-65.62%) paramedic students 80.39% (78.31%-82.36%) ems personnel 51.54% (48.75%-54.32%) chest compression experience < 3 years 71.92% (70.27%-73.52%) chest compression experience > 3 years 62.24% (60.41%-64.05%) ci: confidence interval; ep: electrophysiologist; ems: emergency medical services; aed: automated external defibrillator; iq-cpr meter: improved quality of cardiopulmonary resuscitation meter. table 2: sensitivity and specificity of the iq-cpr meter compared with aed for chest compression depth category sensitivity (95% ci) specificity (95% ci) no light (depth < 5 cm) 32.23 (30.30-34.21) 84.82 (83.62-85.96) green light (depth 5-6 cm) 84.54 (83.32-85.70) 31.35 (29.55-33.37) red light (depth > 6 cm) 1.26 (0.03-6.85) 99.96 (99.88-100.00) ci: confidence interval; aed: automated external defibrillator; iq-cpr meter: improved quality of cardiopulmonary resuscitation meter 3. results 3.1. baseline characteristics of participants there were 27 participants in the study, categorized as faculty members or residents in the ed (7 participants), clinical year medical students (7 participants), paramedic students (7 participants), and ems staff (6 participants). the average age and body mass index (sd) of the participants were 26.00 (5.65) years and 22.93 (3.62) kg/m2. 70.37% (19 participants) were male. the median (1st to 3rd quartile range) of chest compression experience was 3 (1.00-6.50) years. the mean (sd) of chest compression rate was 107 (5.29) times/minute (100 -123). the majority of participants had a chest compression rate between 100-120 times/minute; 25 participants (92.59%). the other two participants had chest compression rate of 121 and 123 times/minute (7.41%). the median (1st to 3rd quartile range) of full recoil rate was 15% (3.00-39.50). 3.2. agreement rate cohen’s kappa coefficient between the iq-cpr meter and the aed was 67.25% (table 1). the subgroup analysis on baseline characteristics showed that cohen’s kappa coefficients ranged from 51.54% to 80.39%: the highest in paramedic students. there were 5,954 chest compressions attempts in the study. the iq-cpr had the highest sensitivity in the green light category (84.54%) and the highest specificity in the red light category (99.96%) as shown in table 2. 4. discussion the iq-cpr meter had fair agreement with the aed device with a cohen’s kappa coefficient of 67.25%. both devices provide real-time feedback on chest compression during cpr. the advantages of iq-cpr meter over the r series®aed include lower cost (83 usd vs 13,333 usd), and being lighter. additionally, the chest compression can be conducted by the bell sound, leading to constant and correct chest compression rate (mean 107 times/minute and 95.59% appropriate rate). for the compression depth, the light indicator indicates real-time compression depth. in contrast, the participants needed to look at the r series®aed screen and interpret if the depth was adequate. as previously reported, a simple light device improved percentage target depth from 48.86% to 72.95%; p 0.036 compared to times when light device was not used (7). the same study also showed that light can improve target rate from 35.82% to 67.09%; p 0.024. this study showed that a simple sound could also lead to adequate chest compression rate as well. the iq-cpr meter uses simple light and sound, real-time audio-visual signals, to lead the participants to perform adequate chest compression in terms of rate and depth. similarly, previous studies showed that real-time audio-visual feedback is crucial and can improve chest compression quality (5, 8, 9). the iq-cpr meter had a high sensitivity (84.54%) for good chest compression depth identified by the green light. therefore, the green light signal by the iq-cpr meter may be a good assistant for chest compression during cpr (table 2). regarding the subgroup analyses, all cohen’s kappa coeffithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. phattharapornjaroen et al. 4 figure 1: area under the curve (auc) of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome. cients were all indicative of good agreement (table 1). note that the paramedic students had a slightly higher coefficient (80.39%). a previous study found that paramedic students may perform better quality cpr compared with medical students (10). the paramedic students had a significantly higher rate of appropriate chest compression depth than medical students in clinical years (50.7 vs 47.3 mm; p 0.01). however, these findings may or may not be related to the highest cohen’s kappa coefficient found in this study. another advantage of the iq-cpr meter is that it can show full recoil of the chest wall through the lever connected to the patch (figure 1). if the chest wall is fully recoiled, the lever will be at the original position. however, it might be slightly difficult to look at the lever and light at the same time during chest compression, resulting in low rate of full recoil in this study (15%). however, there is no evidence of full recoil rate and survival of cardiac arrest patients. there are other cheaper chest compression monitoring devices such as mobile phone or smart watch. a previous study found that smart phone and smart watch had comparable chest compression quality with the manikin system (11, 12). note that audio feedback was given to guide the performer to a compression rate between 100-120 times/minute. for the iq-cpr meter, no audio feedback is needed with the compression rate accuracy of 95.59%. the main strength of this study is the iq-cpr meter, which is cheap and can be a helpful tool for adequate chest compression quality. further studies with real patients may be needed to confirm the results of this study. 5. limitation the main limitation of the iq-cpr meter is that it requires a flat surface for device setup. and, it may not be suitable for children. low body weight may cause instability in the iq-cpr base. finally, there might be some degrees of disagreement between raters, because chest compression depths were defined obviously and clearly by the aed and the iq-cpr. the aed showed compression depth in cm on monitor, while the iq-cpr showed chest compression depth by light (no light, green, and red). therefore, the magnitude of bias is low (95% agreement). 6. conclusion the iq-cpr meter had fair agreement with the computerized chest compression monitoring device, with lower cost and simple, real-time audio-visual feedback. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e76 7. declarations 7.1. acknowledgements we would like to show our gratitude to mr. anusorn adirekkittikun for his help on manufacturing and developing the iq-cpr meter. 7.2. author contribution pp designed the study, analyzed data, interpreted data, and drafted a manuscript; ss collected and interpreted data; pc invented the iq-cpr and interpreted data; ys interpreted data and supervised the research; ks involved in data analysis and drafted a manuscript. all authors read and approved the final manuscript. authors orcids phatthranit phattharapornjaroen: 0000-0002-4391-2929 yuwares sittichabuncha: 0000-0003-1556-4979 kittisak sawanyawisuth: 0000-0003-3570-8474 7.3. funding/support this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.4. conflict of interest the authors report no conflicts of interest. references 1. andersen lw, holmberg mj, berg km, donnino mw, granfeldt a. in-hospital cardiac arrest: a review. jama. 2019;321(12):1200-10. 2. kleinman me, goldberger zd, rea t, swor ra, bobrow bj, brennan ee, et al. 2017 american heart association focused update on adult basic life support and cardiopulmonary resuscitation quality: an update to the american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2018;137(1):e7-e13. 3. kleinman me, brennan ee, goldberger zd, swor ra, terry m, bobrow bj, et al. part 5: adult basic life support and cardiopulmonary resuscitation quality: 2015 american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. circulation. 2015;132(18 suppl 2):s414-35. 4. davey p, whatman c, dicker b. comparison of chest compressions metrics measured using the laerdal skill reporter and q-cpr: a simulation study. simulation in healthcare : journal of the society for simulation in healthcare. 2015;10(5):257-62. 5. kramer-johansen j, myklebust h, wik l, fellows b, svensson l, sorebo h, et al. quality of out-of-hospital cardiopulmonary resuscitation with real time automated feedback: a prospective interventional study. resuscitation. 2006;71(3):283-92. 6. yeung j, davies r, gao f, perkins gd. a randomised control trial of prompt and feedback devices and their impact on quality of chest compressions–a simulation study. resuscitation. 2014;85(4):553-9. 7. gonzalez-calvete l, barcala-furelos r, moure-gonzalez jd, abelairas-gomez c, rodriguez-nunez a. utility of a simple lighting device to improve chest compressions learning. revista espanola de anestesiologia y reanimacion. 2017;64(9):506-12. 8. crowe c, bobrow bj, vadeboncoeur tf, dameff c, stolz u, silver a, et al. measuring and improving cardiopulmonary resuscitation quality inside the emergency department. resuscitation. 2015;93:8-13. 9. hostler d, everson-stewart s, rea td, stiell ig, callaway cw, kudenchuk pj, et al. effect of real-time feedback during cardiopulmonary resuscitation outside hospital: prospective, cluster-randomised trial. bmj (clinical research ed). 2011;342:d512. 10. korber mi, kohler t, weiss v, pfister r, michels g. quality of basic life support a comparison between medical students and paramedics. journal of clinical and diagnostic research : jcdr. 2016;10(7):oc33-7. 11. lu tc, chen y, ho tw, chang yt, lee yt, wang ys, et al. a novel depth estimation algorithm of chest compression for feedback of high-quality cardiopulmonary resuscitation based on a smartwatch. journal of biomedical informatics. 2018;87:60-5. 12. sarma s, bucuti h, chitnis a, klacman a, dantu r. realtime mobile device-assisted chest compression during cardiopulmonary resuscitation. the american journal of cardiology. 2017;120(2):196-200. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2018; 6 (1): e47 or i g i n a l re s e a rc h quetiapine versus haloperidol in controlling conversion disorder symptoms; a randomized clinical trial saeed reza ghanbarizadeh1, hossein dinpanah2∗, reza ghasemi3, yaser salahshour4, samaneh sardashti5, mostafa kamali6, seyed reza khatibi7,8 1. department of urology, 9-day hospital, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 2. emergency department, 9-day hospital, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 3. department of cardiology, 9-day hospital, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 4. department of pediatrics, 9-day hospital, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 5. master of nursing, faculty member, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 6. department of health information technology, torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. 7. department of epidemiology, faculty of health, iran university of medical sciences, tehran, iran. 8. torbat heydariyeh university of medical sciences, torbat heydariyeh, iran. received: july 2018; accepted: august 2018; published online: 2 august 2018 abstract: introduction: about 5% of visits to emergency departments are made up of conversion disorder cases. this study was designed with the aim of comparing the effectiveness of quetiapine and haloperidol in controlling conversion disorder symptoms. methods: the present single-blind clinical trial has been performed on patients with conversion disorder (based on the dsm-iv definition) presenting to emergency department of 9-day hospital, torbat heydariyeh, iran, from january 2017 until may 2018. results: 73 patients were allocated to haloperidol and 71 to quetiapine group. mean age of these patients was 32.03 ± 12.80 years (62.50% female). two groups were similar regarding the baseline characteristics. within 30 minutes, 90.41% of haloperidol cases and 91.55% of quetiapine cases were relieved (p=0.812). the most common side effects after 30 minutes were extrapyramidal symptoms (9.59%) in the haloperidol group and fatigue and sleepiness (7.04%) in the quetiapine group. extrapyramidal symptoms was significantly higher than the quetiapine group (p=0.013). conclusion: the results of the present study showed that although quetiapine and haloperidol have a similar effect in relieving the patients from conversion disorder symptoms, the prevalence of extrapyramidal symptoms is significantly lower in the group under treatment with quetiapine. therefore, it seems that quetiapine is a safer drug compared to haloperidol. keywords: conversion disorder; hysteria; dissociative disorders; quetiapine fumarate; haloperidol; emergency service, hospital © copyright (2018) shahid beheshti university of medical sciences cite this article as: ghanbarizadeh s, dinpanah h, ghasemi r, salahshour y, sardashti s, kamali m, khatibi seyed r. quetiapine versus haloperidol in controlling conversion disorder symptoms; a randomized clinical trial. emergency. 2018; 6(1): e47. 1. introduction conversion disorder is a type of disorder in physical function, which is not in conformity with anatomic and physiologic concepts of central or peripheral nervous system. this ∗corresponding author: hossein dinpanah; emergency department, 9day hospital, torbat heydariyeh, iran. e-mail: foad_0004@yahoo.com tel: +989128435031, +985152282537 disorder occurs as a result of stress and helps alleviate the stress of the patient. this disorder happens in various ages and mostly in young women and individuals with a weakness in coping mechanism (1). conversion disorder is often associated with simultaneous diagnosis of mood disorder, stress disorder, and schizophrenia and its prevalence among the relatives of those affected with these disorders is higher than the general population (2). a significant symptom of these disorders is involuntary loss of function or action disorder in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. ghanbarizadehi et al. 2 the function of voluntary nervous system. usually, the symptoms of this disease manifest suddenly and due to extreme and exciting conditions; including numbness or paralysis in hand and foot, fainting, etc. sometimes the symptoms of hysteria disappear at the same speed they were manifested and they can usually be relieved or completely resolved via suggestion (3). statistics indicate that about 5% of visits to emergency departments are made up of conversion disorder cases (4). there is no specific guideline for management of these patients in the emergency department. anti-stress drugs lead to a decrease in stress of the patients and consequently cause improvement in conversion disorders (4-6). haloperidol is a traditional anti-psychotic drug that is used for treatment of various psychiatric disorders (7, 8). better effectiveness of this drug compared to diazepam in treatment of conversion disorder has been confirmed (9) but its side effects including extrapyramidal symptoms is a serious limitation for its application (10, 11) and therefore, researchers are looking for new drugs to replace it. quetiapine is an atypical anti-psychotic drug used for treatment of schizophrenia, bipolar disorder, and prescribed in association with an antidepressant drug for treatment of depression disorder. effectiveness of quetiapine in treating psychological disorders has been witnessed, especially in mood and anxiety disorders (12). this drug exerts its anti-psychotic effects via a direct antagonistic effect on dopaminergic and serotonin receptors. therefore, it might be beneficial in treatment and control of conversion disorders. the present study was designed with the aim of comparing the effectiveness of quetiapine and haloperidol in controlling conversion disorder symptoms in patients presenting to the emergency department. 2. methods 2.1. study design and setting the present single-blind clinical trial has been performed on patients with conversion disorder in 9-day hospital, torbat heydariyeh, iran, from january 2017 until may 2018. diagnosis of conversion disorder was done based on the 4th edition of diagnostic and statistical manual of mental disorders (dsm-ivtr, 2000). ethics committee of torbat heydariyeh university of medical sciences approved the protocol of the present study. this clinical trial has been registered on irct with following code: irct2015100712050n2. the researchers adhered to the principles of helsinki declaration throughout the study period. 2.2. participants the studied participants included those affected with conversion disorder diagnosed by an emergency medicine physician based on dsm-iv definitions. exclusion criteria are shown in table 1. sampling was done via convenience method. patients who had one of the following conditions were excluded from the study: no definite diagnosis of conversion disorder, patients with problems in vital signs, critically ill patients, those aged under 18 years and over 60 years, pregnant and lactating patients, addicts, those not participating or not tolerating oral medication, being affected with acute cardiopulmonary, liver, or kidney diseases, history of parkinson, history of epilepsy or taking anti-epileptic drugs, history of hypothyroidism, hypokalemia, hypomagnesemia, familial long qt syndrome, simultaneous treatment with other neuroleptic drugs of drugs that elongate qt interval, allergy to neuroleptic drugs and benzodiazepines. 2.3. intervention patients underwent treatment with haloperidol or quetiapine via block randomization with size 6 blocks (using a computer program). iv haloperidol with 5mg dose (manufactured by caspian company, rasht, iran) and rapid-releasing oral quetiapine with 50 mg dose (manufactured by tehran shimi, tehran, iran) were prescribed. the present study was designed as a single-blind one in which the patient was blind to the drug prescribed. drugs were prepared as colorless and anonymous packs and injected to the patients. 2.4. outcome the evaluated outcomes included being relieved from conversion disorder symptoms and presentation of side effects. side effects were reported in 4 groups of extrapyramidal symptoms, fatigue and sleepiness, headache, and other. patients were evaluated 30 minutes and 24 hours after drug prescription. 2.5. data gathering for gathering data, a pre-designed checklist consisting of demographic data, history of mental diseases, symptoms on admission, response to treatment, and side effects 30 minutes and 24 hours after treatment was used. an emergency medicine specialist was responsible for data gathering. 2.6. statistical analysis sample size was calculated based on treatment success of haloperidol (28%) and quetiapine (55%) in alleviating psychotic symptoms (13). therefore, considering α=0.05 and β=0.1, the required sample size in each group was considered 68 patients. data were analyzed via stata 14.0 software and with intention to treat analysis approach. results were reported as mean ± standard deviation or frequency and percentage. t-test was applied for comparing quantitative data, and chi-square or fisher’s exact tests were used to compare the frequency between the 2 groups. in all analyses, p<0.05 was considered as level of significance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e47 3. results 3.1. baseline characteristics of the patients throughout the study period, 144 patients were evaluated. 73 patients were allocated to haloperidol group and 71 patients were in the quetiapine group. mean age of these patients was 32.03 ± 12.80 years and 62.50% of the patients were female. age (p=0.654) and sex (p=0.414) distribution were not different between the 2 groups. 12 (16.44%) patients in the haloperidol group and 6 (8.45%) patients in the quetiapine group had a history of psychotic disorders (p=0.147). the most common presentation of the patients on admission to emergency department were non-paralysis (25.69%) and epileptic seizure (9.72%) (p=0.584). table 1 depicts the distribution of baseline characteristics of the patients in the 2 treatment groups. 3.2. outcomes within 30 minutes after prescription of haloperidol and quetiapine, respectively, 90.41% and 91.55% of the patients in each group were relieved of conversion disorder symptoms (p=0.812). it should be noted that 30 minutes (p=0.412) and 24 hours (p=0.940) after prescription of drugs the overall prevalence of side effects was not different between the 2 groups (table 2). the most common side effects after 30 minutes after prescription of the drugs were extrapyramidal symptoms (9.59%) in the group under treatment with haloperidol and fatigue and sleepiness (7.04%) in the group treated with quetiapine (table 3). analyses showed that prevalence of extrapyramidal symptoms as side effects in haloperidol group was significantly higher than the group treated with quetiapine at this time (p=0.013). although 24 hours after drug administration the prevalence of extrapyramidal symptoms in haloperidol group was still higher than quetiapine group (8.22% vs. 1.41%), this difference was not significant (p=0.116). 4. discussion the results of the present study showed that although quetiapine and haloperidol have a similar effect in relieving the patients from conversion disorder symptoms, the prevalence of extrapyramidal symptoms is significantly lower in the group under treatment with quetiapine. therefore, it seems that quetiapine is a safer drug compared to haloperidol. effectiveness and safety of quetiapine have been evaluated in controlling the symptoms of various mental diseases, but to the best our knowledge, the role of this drug in controlling conversion disorder is evaluated in the present study for the first time. however, there are studies available that have assessed the effectiveness of quetiapine and haloperidol in controlling the symptoms of other mental diseases. for example arvanitis et al. showed that quetiapine is superior to haloperidol in 150 to 750 mg/day doses compared to placebo and haloperidol in treating acute exacerbation of schizophrenia (14). in addition, in their study, velligan et al. showed that quetiapine is more effective than haloperidol in improving the cognitive function of schizophrenia patients (15). however, delmonte et al. showed that haloperidol is more effective in treating severe mania compared to quetiapine (16). yet, verachai et al. express that the effectiveness and side effects of haloperidol and quetiapine in treatment of methamphetamine-induced psychosis are similar (17). on the other hand, emsley et al. express that quetiapine has both more effectiveness and less extrapyramidal side effects in controlling the symptoms of schizophrenia compared to haloperidol (18). as can be seen, the effectiveness of quetiapine and haloperidol varies in treatment and control of different mental disease symptoms and there is a lot of disagreement between the studies. in one of the studies performed with the aim of comparing prescription of quetiapine and venlafaxine in treating the symptoms of somatization, it was determined that although quetiapine leads to improvement of these symptoms, it has a lower effectiveness compared to venlafaxine (19). in addition, jin-long et al. showed that low doses of quetiapine are effective in treatment of somatization disorder. the researchers mentioned safety and rapid effect as the pros of this drug (20). since conversion disorder is one of the subsets of somatization disorders it can be said that the 2 mentioned studies are in line with the present study. quetiapine results in less extrapyramidal side effects compared to haloperidol in controlling the effects of conversion disorder. this is one of the strong points of this drug because extrapyramidal symptoms are the most important side effect that limits the use of haloperidol. dyskinesia, dystonia, akinesia, and neuroleptic malignant syndrome are among the side effects that require emergency care (21) and if a drug is available that reduces these symptoms, it will be very useful in clinic. in the present study, only 1 case of extrapyramidal side effects was observed in the quetiapine group, while there were 13 patients who were affected by these side effects as a result of consuming haloperidol. this significant difference results in quetiapine being introduced as a proper replacement for haloperidol. 5. limitation among the limitations of the present study is the absence of placebo arm. since from an ethical point of view it is not possible to leave a group of patients untreated, this could not be done. among other limitations of this study was the short duration of follow-up for the patients. since the half-life of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. ghanbarizadehi et al. 4 table 1: baseline characteristics of conversion disorder patients variable haloperidol n=73 quetiapine n=71 total n=144 p age (mean, sd; years) 31.56±12.18 32.52±13.47 32.03±12.80 0.654 sex (n, %) male 25 (34.25) 29 (40.85) 54 (37.50) 0.414 female 48 (65.75) 42 (59.15) 90 (62.50) psychotic disorders’ history (n, %) no 61 (83.56) 65 (91.55) 126 (87.50) yes 12 (16.44) 6 (8.45) 18 (12.5) 0.147 presentation on admission (n, %) non-epileptic seizure 6 (8.22) 8 (11.27) 14 (9.72) speech disorder 8 (10.96) 4 (5.63) 12 (8.33) 0.584 paralysis 17 (23.29) 20 (28.17) 37 (25.69) other 42 (57.53) 39 (54.93) 81 (56.25) table 2: success of haloperidol and quetiapine in alleviating conversion disorder symptoms variable haloperidol n=73 quetiapine n=71 total n=144 p response to treatment (n, %) no 7 (9.59) 6 (8.45) 13 (9.03) 0.812 yes 66 (90.41) 65 (91.55) 131 (90.97) side effect (n,%) 30 min no 65 (89.04) 66 (92.96) 131 (90.97) 0.412 yes 8 (10.96) 5 (7.04) 13 (9.03) 24 hours no 64 (87.67) 62 (87.32) 126 (87.50) 0.950 yes 9 (12.33) 9 (12.68) 18 (12.50) table 3: comparison of haloperidol and quetiapine side effects in alleviating conversion disorder symptoms variable haloperidol n=73 quetiapine n=71 total n=144 p* 30 min (n, %) extrapyramidal symptoms 7 (9.59) 0 (0.00) 7 (4.86) 0.013 fatigue and sleepiness 3 (4.11) 5 (7.04) 8 (5.46) 0.491 headache 2 (2.74) 1 (1.41) 3 (2.08) >0.999 other 3 (4.11) 0 (0.00) 3 (2.08) 0.245 24 hours (n, %) extrapyramidal symptoms 6 (8.22) 1 (1.41) 7 (4.86) 0.116 fatigue and sleepiness 6 (8.22) 6 (8.45) 12 (8.33) >0.999 headache 2 (2.74) 2 (2.82) 4 (2.78) >0.999 other 1 (1.37) 0 (0.00) 1 (0.69) >0.999 * , based on fisher’s exact test haloperidol in body is 48 hours, 48-hour follow-up of the patients might present different results. 6. conclusion the results of the present study showed that although quetiapine and haloperidol have a similar effect in relieving the patients from conversion disorder symptoms, the prevalence of extrapyramidal symptoms is significantly lower in the group under treatment with quetiapine. therefore, it seems that quetiapine is a safer drug compared to haloperidol. 7. appendix 7.1. acknowledgements the authors would like to thank the emergency department staff of 9-day hospital. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e47 7.2. author contribution all the authors of this article met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. 7.3. funding/support none. 7.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. ruddy r, house a. psychosocial interventions for conversion disorder. cochrane database syst rev. 2004;4. 2. torgersen s. genetics and somatoform disorders. tidsskrift for den norske laegeforening: tidsskrift for praktisk medicin, ny raekke. 2002;122(14):1385-8. 3. lee d. hysteria today. taylor & francis; 2017. 4. folks dg, ford cv, regan wm. conversion symptoms in a general hospital. psychosomatics. 1984;25(4):294-5. 5. wald j, taylor s, scamvougeras a. cognitive behavioural and neuropsychiatric treatment of post-traumatic conversion disorder: a case study. cognitive behaviour therapy. 2004;33(1):12-20. 6. moene fc, spinhoven p, hoogduin ka, van dyck r. a randomised controlled clinical trial on the additional effect of hypnosis in a comprehensive treatment programme for in-patients with conversion disorder of the motor type. psychotherapy and psychosomatics. 2002;71(2):6676. 7. crum w, danckaers f, huysmans t, cotel m-c, natesan s, modo m, et al. chronic exposure to haloperidol and olanzapine leads to common and divergent shape changes in the rat hippocampus in the absence of grey-matter volume loss. psychological medicine. 2016;46(15):3081-93. 8. hui d, frisbee-hume s, wilson a, dibaj ss, nguyen t, de la cruz m, et al. effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. jama. 2017;318(11):1047-56. 9. budden m. a comparative study of haloperidol and diazepam in the treatment of anxiety. current medical research and opinion. 1979;5(10):759-65. 10. rasmussen sa, rosebush pi, mazurek mf. the relationship between early haloperidol response and associated extrapyramidal side effects. journal of clinical psychopharmacology. 2017;37(1):8-12. 11. ribeiro sb, de araujo aa, medeiros cax, chaves km, alves mdscf, oliveira ag, et al. factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics. european journal of clinical pharmacology. 2017;73(3):351-5. 12. altamura ac, moliterno d, paletta s, buoli m, dell’osso b, mauri mc, et al. effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach. clinical drug investigation. 2012;32(3):213-9. 13. emsley r, turner hj, schronen j, botha k, smit r, oosthuizen pp. a single-blind, randomized trial comparing quetiapine and haloperidol in the treatment of tardive dyskinesia. j clin psychiatry. 2004;65(5):696-701. 14. arvanitis la, miller bg. multiple fixed doses of &#x201c;seroquel&#x201d; (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. biological psychiatry. 1997;42(4):233-46. 15. velligan di, newcomer j, pultz j, csernansky j, hoff al, mahurin r, et al. does cognitive function improve with quetiapine in comparison to haloperidol? schizophrenia research. 2002;53(3):239-48. 16. delmonte d, de santis c, brioschi s, barbini b, colombo c. haloperidol, risperidone and quetiapine in the treatment of acute severe manic episode in bipolar disorder: the experience at the mood disorder unit in milan. european psychiatry. 2016;33:s125-s6. 17. verachai v, rukngan w, chawanakrasaesin k, nilaban s, suwanmajo s, thanateerabunjong r, et al. treatment of methamphetamine-induced psychosis: a double-blind randomized controlled trial comparing haloperidol and quetiapine. psychopharmacology. 2014;231(16):3099-108. 18. emsley ra, raniwalla j, bailey pj, jones am. a comparison of the effects of quetiapine (’seroquel’) and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. prize study group. international clinical psychopharmacology. 2000;15(3):121-31. 19. zhang c, he z, sun y. quetiapine in the treatment of somatoform disorder. china journal of health psychology 2013;2013(11):1629-31. [chinese]. 20. jin-long w, he-dan z. synergistic effects by small dosage of quetiapine in treatment of somatization disorders. herald of medicine. 2011;6:21. 21. kamin j, manwani s, hughes d. emergency psychiatry: extrapyramidal side effects in the psychiatric emergency service. psychiatric services. 2000;51(3):287-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e28 ca s e re p o rt rectus muscle hematoma as a rare differential diagnosis of acute abdomen; a case report mohammadreza maleki verki1, hassan motamed1∗ 1. emergency medicine department, ahvaz jundishapur university of medical sciences, ahvaz, iran. received: april 2018; accepted: may 2018; published online: 1 may 2018 abstract: rectus sheath hematoma is a rare but well-known problem. exercise, pregnancy, subcutaneous injection of insulin, abdominal surgery and severe coughs can be predisposing factors of hemorrhage in the mentioned muscle sheath. here, we will discuss a case of rectus sheath hematoma in a 28 year-old female patient who presented to emergency department with complaint of abdominal pain and improved in 1 week with palliative care. keywords: rectus abdominis; hemorrhage; abdomen, acute; emergency service, hospital; ultrasonography © copyright (2018) shahid beheshti university of medical sciences cite this article as: maleki verki m, motamed h. rectus muscle hematoma as a rare differential diagnosis of acute abdomen; a case report. emergency. 2018; 6 (1): e28. 1. introduction rectus sheath hematoma is a rare but well-known problem (1, 2). exercise, pregnancy, subcutaneous injection of insulin, abdominal surgery and severe coughs can be predisposing factors of hemorrhage in the mentioned muscle sheath (1-6). acute abdominal pain and mass are among the most important clinical manifestations of rectus sheath hematoma that can be mistaken for cases such as appendicitis, abscesses and abdominal wall tumors, hernias, and diverticular diseases as well as gynecologic and urinary tract diseases in differential diagnosis (7, 8). here, we will discuss a case of rectus sheath hematoma in a 28 year-old female patient who presented to emergency department with complaint of abdominal pain and improved in 1 week with palliative care. 2. case report the patient is a 28 year-old female who presented to the emergency department with acute abdominal pain since 2 hours before. abdominal pain in the patient was under the umbilicus and on both sides of the central line of the abdomen or linea alba, localized, and without diffusion to a special point. the pain was not related to eating but would ∗corresponding author: hassan motamed; emergency department, golestan hospital, golestan, farvardin avenue, ahvaz, iran. tel: +989123169951 email: hasan_motamed@yahoo.com worsen with walking and change in position. as the patient said, the pain had manifested suddenly following the second session of working out while she was doing sit-ups and she could not continue exercising. the patient did not mention complaints of nausea or vomiting, urinary symptoms such as burning or frequent urination, vaginal discharge or history of direct trauma to the abdomen. her menstrual cycle was regular and she reported the time of her last menstruation as 20 days before. she had a history of consuming accutane drug until 2 months before due to acne. she did not mention any history of bleeding disorders in herself or her family. vital signs of the patient on admission to the emergency department were: blood pressure, 100/80 mmhg, heart rate 90 per minute, respiratory rate 10 per minute, oxygen saturation 98% at room temperature and sublingual temperature of 37 ◦c. abdominal examination indicated localized bilateral tenderness under the umbilicus, without rebound and no mass was sensed. there was no sign of bruise, scar, or skin lesions on the abdomen. examination of other organs and gynecologic examination had no pathologic finding. coagulation, blood and urine tests were normal and serum îšhcg was negative. in the ultrasonography performed on the patient, 2 heterogenic hypo-echo regions were seen. one was 9×22×23 millimeters in size (approximate volume of 2.5 cc) in the right rectus muscle and the other with approximate dimensions of 4×25×45 (approximate volume of 3 cc) in the left rectus muscle 13 mm from the skin surface with the approximate disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. maleki varaki and h. motamed 2 figure 1: ultrasonography view of hematoma in rectus muscle sheath of the patient tance of 10 cm under the umbilicus, which suggested rectus hematoma (figure 1). no other ultrasonography abnormality was detected in the appendix, ovaries and vagina. finally, the patient was discharged from the emergency department with diagnosis of rectus muscle hematoma and with prescription of oral analgesics and order to rest. 1-week follow up of the patient revealed gradual pain relief during the initial 48 hours and complete relief within a week. 3. discussion rectus muscle sheath hematoma occurs due to rupture of upper and lower epigastric arteries and their branches or rupture of the rectus muscles themselves (9). sudden muscle strain and change in position without direct trauma are usually predisposing factors of bleeding in muscle sheath (10). in most cases, rectus muscle hematomas are self-limiting and are conservatively absorbed via rest and use of analgesics (11). when a patient is hemodynamically unstable, the size of hematoma is increasing or rupture has happened in the peritoneum, there is a need to consult the surgery service (1, 12, 13). anyway, the important point is to have this differential diagnosis in mind along with other pathologies of acute abdomen and especially hernia, patients affected with which usually present with similar history. abdominal ultrasonography as an available bedside tool is also very helpful in this case under the condition that the operator also looks for surface pathologies having this differential diagnosis in mind (14). like other diseases, accurate history taking along with clinical suspicion will lead to finding the key to the mystery more rapidly. 4. appendix 4.1. acknowledgements all the staff members of the emergency department of golestan hospital, ahvaz, iran are thanked for their cooperation. 4.2. authors contribution all the authors of this article met the criteria of authorship based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. 4.4. funding and support none. references 1. cherry wb, mueller ps. rectus sheath hematoma: review of 126 cases at a single institution. medicine. 2006;85(2):105-10. 2. maharaj d, ramdass m, teelucksingh s, perry a, naraynsingh v. rectus sheath haematoma: a new set of diagnostic features. postgraduate medical journal. 2002;78(926):755-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e28 3. linhares mm, lopes filho gj, bruna pc, ricca ab, sato ny, sacalabrini m. spontaneous hematoma of the rectus abdominis sheath: a review of 177 cases with report of 7 personal cases. international surgery. 1999;84(3):251-7. 4. buckingham r, dwerryhouse s, roe a. rectus sheath haematoma mimicking splenic enlargement. journal of the royal society of medicine. 1995;88(6):334-5. 5. zainea gg, jordan f. rectus sheath hematomas: their pathogenesis, diagnosis, and management. the american surgeon. 1988;54(10):630-3. 6. james rf. rectus sheath haematoma. lancet (london, england). 2005;365(9473):1824. 7. edlow ja, juang p, margulies s, burstein j. rectus sheath hematoma. annals of emergency medicine. 1999;34(5):671-5. 8. lohle pn, puylaert jb, coerkamp eg, hermans et. nonpalpable rectus sheath hematoma clinically masquerading as appendicitis: us and ct diagnosis. abdominal imaging. 1995;20(2):152-4. 9. riaz a, phylactides l, smith f, cheng k, law n, hamilton h. spontaneous rectus sheath haematoma mimicking an enlarged urinary bladder. hospital medicine. 2000;61(10):739-. 10. berna j, garcia-medina v, guirao j, garcia-medina j. rectus sheath hematoma: diagnostic classification by ct. abdominal imaging. 1996;21(1):62-4. 11. zainea g, jordan f. rectus sheath hematomas: their pathogenesis, diagnosis, and management. the american surgeon. 1988;54(10):630-3. 12. smithson a, ruiz j, perello r, valverde m, ramos j, garzo l. diagnostic and management of spontaneous rectus sheath hematoma. european journal of internal medicine. 2013;24(6):579-82. 13. salemis ns, gourgiotis s, karalis g. diagnostic evaluation and management of patients with rectus sheath hematoma. a retrospective study. international journal of surgery. 2010;8(4):290-3. 14. klingler p, wetscher g, glaser k, tschmelitsch j, schmid t, hinder r. the use of ultrasound to differentiate rectus sheath hematoma from other acute abdominal disorders. surgical endoscopy. 1999;13(11):1129-34. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case report discussion appendix references emergency. 2018; 6 (1): e51 or i g i n a l re s e a rc h serum procalcitonin and lactoferrin in detection of acute appendicitis; a diagnostic accuracy study mohammad reza motie1, anvar soleimani2,3, arash soltani2,3, seyed isaac hashemy1,2∗ 1. surgical oncology research centre, mashhad university of medical sciences, mashhad, iran. 2. department of clinical biochemistry, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. student research committee, mashhad university of medical sciences, mashhad, iran. received: apirl 2018; accepted: august 2018; published online: 25 august 2018 abstract: introduction: finding an accurate diagnostic test can reduce the rate of unnecessary abdominal surgery in cases of suspected acute appendicitis (aa). this study aimed to evaluate the diagnostic value of serum lactoferrin (lf) and procalcitonin (pct) in detection of patients with acute appendicitis. methods: in this diagnostic accuracy study, screening performance characteristics of pct and lf were calculated in patients suspected with acute appendicitis and healthy volunteers as control group. results: 131 cases participated (61 as case and 70 as control). the mean serum level of lf (0.9±0.14 vs 0.2±0.13 µg/ml; p 0.0001) and pct (0.15±0.21 vs 0.11±0.02 ng/dl; p = 0.02) were significantly higher in patients suspected with aa. the auc of pct and lf were 0.46 (95% ci: 0.31-0.61) and 0.61 (95%ci: 0.47 0.76), respectively. at a 0.90 µg/ml cut-off value, lf had 77% (95 % ci: 63 91) sensitivity and 43% (95% ci: 31 55) specificity. also, at a 0.11 ng/dl cut-off value, pct had 41% (95% ci: 26 56) sensitivity and 69% (95% ci: 53 85) specificity. conclusion: based on the main finding of present study, the overall accuracy of serum pct and lf in detection of patients with acute appendicitis are in poor to failed range and it seems that they could not be considered as good screening tools for this purpose. keywords: diagnosis; marker; procalcitonin; lactoferrin; acute appendicitis © copyright (2018) shahid beheshti university of medical sciences cite this article as: motie m r, soleimani a, soltani a, hashemy s i. serum procalcitonin and lactoferrin in detection of acute appendicitis; a diagnostic accuracy study. emergency. 2018; 6(1): e51. 1. introduction a cute appendicitis (aa) is the most common abdominal emergency worldwide with a significant morbidity and mortality rate. it requires abdominal surgery with an overall lifetime risk of 8.6% in males and 6.7% in females (1, 2). the diagnosis of acute appendicitis is challenging and may be the most common diagnostic problem in clinical surgery (3). late diagnosis and delay in surgery of aa may result in ruptured appendicitis, systemic septic complications and a longer stay at hospital. abdominal pain is a common cause for visiting in the emergency department (ed). the initial clinical sign of appendicitis is pain in the lower right quadrant of abdomen or periumbilical pain, followed by nausea, vomiting and fever. ∗corresponding author: seyed isaac hashemy; surgical oncology research centre, mashhad university of medical sciences, mashhad, iran. email: hashemyi@mums.ac.ir tel: +98-9158112664 this event occurs approximately in 50% of adults (4). however, the mentioned symptoms are associated with a variety of pathologies and they do not have sufficient specificity and sensitivity; therefore, clinical diagnosis of aa from other pathologies can be challenging and may finally lead to unnecessary appendectomy. the diagnosis of aa is usually confirmed by conventional biomarkers including c-reactive protein (crp), white blood cell count (wbc), body temperature (bt) and absolute neutrophil count (anc) (5). since advances in radiographic imaging, such as ultrasound and ct scan, have improved the accuracy of diagnosis of aa, the rate of unnecessary appendectomy has decreased. however, studies have shown that the prevalence of unnecessary appendectomy is around 45%, which is particularly common in females (1, 4). therefore, researchers have tried for decades to find diagnostic markers to increase the accuracy and safety of clinical diagnosis of aa. several studies have shown that serum level of procalcitonin (pct) and lactoferrin (lf) increase during bacterial infecthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m r. motie et al. 2 tions (2, 8, 9). pct, a precursor of calcitonin, is secreted by c cells of thyroid gland under normal conditions, and it has been demonstrated to be one of the most important laboratory markers for the presence of fungal and bacterial diseases. unlike other clinical biomarkers such as crp, the level of procalcitonin does not change in patients with nonbacterial and viral infections, which makes it an appropriate biomarker for aa (10, 11). a lot of studies have assessed the value of pct for diagnosing and determining the severity of acute appendicitis, but the results have been contradictory and the diagnostic value of procalcitonin in appendicitis is still unclear (8, 12). lf is a glycoprotein with a molecular weight of 78 kd. it has antibacterial properties and acts against a wide range of gram-positive and gram-negative bacteria. lf is released exactly like other neutrophil proteins following neutrophil activity, as seen in individuals with inflammatory bowel disease, and it quickly appears in the feces (13, 14). both pct and lf are released after neutrophil activation, and their plasma level can be measured in the serum or plasma (15). based on the above-mentioned points, we decided to evaluate the diagnostic value of serum lf and pct in discrimination of patients with acute appendicitis among suspected cases. 2. methods 2.1. study design and setting in this diagnostic accuracy study, patients suspected with acute appendicitis (based on a primary diagnosis by physicians), who had been referred to imam reza hospital, mashhad, iran, from september 2015 to september 2017 were included. the study protocol was approved by the ethics committee of mashhad university of medical sciences and written informed consent was taken from each patient. 2.2. participants patients more than 16 years old with acute abdominal pain, who had been referred to emergency department of mentioned hospital, were included using convenience sampling method. in addition, 70 healthy volunteers including males and females whose sex and age were matched with patients were enrolled as the control group. patients with any evidence of other diseases such as cancer, inflammatory bowel disease, consumption of steroidal or non-steroidal anti-inflammatory drugs and antibiotics before their hospitalization, patients without any pathological findings, patients with reactive follicular hyperplasia or chronic appendicitis, and those with certain infectious diseases were excluded. 2.3. procedure suspected patients were primarily detected at the emergency triage unit, and then were examined by a surgeon. alvarado score (16) was recorded for all patients, and appendectomy was carried out based on the routine surgery department protocol. blood samples for laboratory tests were collected from all patients on admission before appendectomy. serum pct and lf levels were measured by commercially available elisa kits from hycult biotechnology (cat # hk329-01) for lf and abcam (cat #ab221828) for pct. after appendectomy, a histopathology study was conducted on all samples, and the results were categorized into one of the 5 following groups by a pathologist: patients without any pathological findings (group 1); patients with reactive follicular hyperplasia or chronic appendicitis (group 2); patients with acute appendicitis, intact appendix mucosa and a mild to moderate infiltration of the inflammatory cells (group 3); patients with macroscopically or histologically perforated acute appendicitis, or perforated appendix mucosa accompanied by a strong pan-mural infiltration of the inflammatory cells (group 4); and finally, patients with acute necrotizing appendicitis (group 5). the alvarado scores less than 4 were defined as unlikely in terms of appendicitis, scores of 5-6 as poor possibility of appendicitis, scores of 7-8 likely and scores of 9-10 were described as high possibility of appendicitis. 2.4. reference test the surgical histopathology finding was used as the confirmative test for diagnosis of acute appendicitis. 2.5. data gathering demographic information (age, sex), vital signs (temperature, heart rate, respiratory rate), white blood cell count (wbc), neutrophil count, serum level of lf and pct, patients’ alvarado score, as well as the results of surgical histopathology of appendix were recorded for all participants using a pre-designed checklist. there were no missing data. all data were collected prospectively by a trained pathology resident. 2.6. statistical analysis due to the small sample size of our study, bootstrap resampling method was carried out to obtain 95% biascorrected confidence intervals for each area under the roc curve (auc) (17). an evaluation for the cut-off value of the biomarkers for the acute appendicitis diagnosis was defined by the youden index (18). statistical tests (chi-squared, fisher’s exact, logistic regression and independent t-test as well as mann whitey u test (non-parametric independentpaired comparison)) were used for analyses. receiver opthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e51 erator characteristic (roc) curves were drawn to calculate the diagnostic accuracy of the studied serum biomarkers (lf, pct) with 95% confidence interval (ci). a p value < 0.05 was considered statistically significant. statistical analysis was performed using spss11 software, and data were presented as mean ± standard deviation or frequency (%). the correlation of lf, pct with pathology and alvarado scores as well as wbc and neutrophil counts was investigated in suspected acute appendicitis cases. 3. results 3.1. baseline characteristics 105 cases were detected as patients suspected to have acute appendicitis, 80 of which were eligible for inclusion in the study. 19 (18.1%) patients were pathologically categorized into non-acute group and 61 patients were confirmed as acute appendicitis based on surgical histopathology. baseline characteristics of studied patients are listed in table 1. the group suspected with aa and control group were similar regarding mean age (26.32±10.67 vs 28.97±9.63; p = 0.115) and male to female ratio (34/27 vs 34:36; p = 0.319). the mean serum level of lf (0.9±0.14 vs 0.2±0.13 µg/ml; p 0.0001) and pct (0.15±0.21 vs 0.11±0.02 ng/dl; p = 0.02) were significantly higher in patients suspected with aa. 3.2. relationships there was no correlation between serum pct level and alvarado score (r= 0.12, p=0.5), pathology grade (r=0.01, p=0.31), wbc count (r= 0.06, p=0.57), and neutrophil count (r= 0.13, p=0.27). in addition, there was no correlation between serum lf level and alvarado score (r= 0.21, p=0.12), pathology grade (r= 0.19, p=0.10), wbc count (r= 0.13, p=0.23), and neutrophil count (r= 0.17, p=0.15). the correlation coefficient between procalcitonin and lactoferrin was 0.02 (p=0.834). 3.3. screening performance characteristics of evaluated parameters the auc of pct and lf were 0.46 (95% ci: 0.31-0.61) and 0.61 (95%ci: 0.47 0.76), respectively. at a 0.90 µg/ml cut-off value, lf had 77% (95% ci: 63 91) sensitivity, 43% (95% ci: 31 55) specificity, 0.71 (95% ci: 0.65-0.78) positive predictive value, 0.29 (ci 95%:0.23-0.35) negative predictive value, 1.35 (95% ci: 1.12-1.58) positive likelihood ratio, and 0.53 (95% ci: 0.46-0.60) negative likelihood ratio. also, at a 0.11 ng/dl cut-off value, pct had 41% (95% ci: 26 56) sensitivity, 69% (95% ci: 53 85) specificity, 0.45 (95% ci: 0.38-0.52) positive predictive value, 0.04 (ci 95%: 0.020.06) negative predictive value, 1.32 (95% ci: 1.10-1.60) positive likelihood ratio, and 0.85 (95% ci: 0.55-1.25) negative table 1: baseline characteristics of patients suspected with acute appendicitis (aa) (n=80) baseline characteristics suspected to aa age (year) mean ± sd 26.32±10.67 sex male/female ratio 34:27 temperature (c) mean ± sd 37.22± 0.63 wbc (103 mm3 ) mean ± sd 13.28±4.1 neutrophil (%) mean ± sd 76.05±16 symptoms n (%) shifting pain 62 (77.5) nausea-vomit 67 (83.8) anorexia 69 (86.3) lactoferrin (µg/ml) mean ± sd 0.9±0.14 procalcitonin (ng/dl) mean ± sd 0.15±0.21 alvarado-score n (%) <4 1 (1.3) 5-6 20 (25) 7-8 26 (32.5) 9-10 33 (41.3) pathology score n (%) 1 2 19 (23.8) 3 10 (12.5) 4 48 (60) 5 3 (3.8) figure 1: area under the roc curve of lactoferrin, procalcitonin, white blood cell count, neutrophil count, and alvarado score in detection of patients with acute appendicitis. likelihood ratio. table 2 and figure 1 show the screening performance characteristics of wbc, neutrophil count, and alvarado score for comparison with pct and lf. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m r. motie et al. 4 table 2: screening performance characteristics of lactoferrin (µg/ml), procalcitonin (ng/dl), white blood cell (wbc) count (× 103 mm3 ), neutrophil count, and alvarado score in detection of patients with acute appendicitis variable cut-off sensitivity specificity auc lactoferrin 0.90 77(6391) 43(31-55) 0.61 (0.47 0.76) procalcitonin 0.11 41(26-56) 69(53-85) 0.46 (0.31-0.61) wbc count 10 85(72-98) 45(32-58) 0.70 (0.57-0.83) neutrophil 75 72( 60-84) 69(52-86) 0.71 (0.58-0.84) alvarado 7 95(91-99) 22(16-28) 0.66 (0.50-0.81) all measures were presented with 95% confidence interval. auc: area under the roc curve. 4. discussion diagnosis of patients with appendicitis is a big challenge in emergency department; therefore, a lot of negative appendectomies have been observed. a correct and early diagnosis of the disease is vital to decrease its morbidity of perforated cases and also to prevent unnecessary surgery for misdiagnosed cases (6). in this regard, a lot of clinical studies have been carried out in order to identify gold markers to reach a better diagnosis. the most accurate clinical biomarkers presented for diagnosis of this disease are crp and wbc. however, they do not have the ability to discriminate all true patients among suspected subjects (8, 19). in our study, we measured the serum level of lactoferrin and procalcitonin between suspected acute appendicitis cases and healthy controls. the comparison of these biomarkers showed a significant difference between patients with acute appendicitis and healthy controls. in consistence with our study, another study on new biomarkers for acute appendicitis showed a significant difference of lactoferrin between acute appendicitis and healthy controls (9). in another study, the plasma level of procalcitonin in patients with confirmed acute appendicitis was reported to be more than the control group (0.5 ng/ml serum level for patients) (20). we evaluated the correlation of lactoferrin and procalcitonin with eachother and other criteria including wbc, neutrophil count and alvarado score. we could not find any correlation between these parameters. we separated the acute appendicitis cases from nonappendicitis via pathology score after appendectomy. roc curve analysis showed the best accuracy test for diagnosis of appendicitis is neutrophil count with the auc of 0.71 and at a defined cut-off of 75%; sensitivity and specificity were 72% and 69%, respectively. the accuracy of test for lactoferrin and procalcitonin were 0.61 and 0.46, respectively. since auc represents the accuracy of the test and auc of less than 0.5 is not statistically appropriate for diagnosis of disease, the serum level of procalcitonin is not a good diagnostic factor. however, in one study procalcitonin is introduced as a diagnostic marker for acute appendicitis with a sensitivity of 95.65% and a specificity of about 100% (11). moreover,in another study the pct value of > 0.5 ng/ml is shown to be useful for diagnosis of appendicitis with 73% sensitivity and 94% specificity (21). khan et al. showed that the serum level of procalcitonin in children with suspected acute appendicitis is higher than control group (1.12 ng/ml ± 3.28 versus 0.45 ng/ml ± 1.12), but it is not statistically significant (p=0.3) (22). the interesting point about procalcitonin is the high specificity in all studies that suggest it as a diagnostic biomarker along with other parameters with high sensitivity such as wbc, crp and neutrophil count. the accuracy test for lactoferrin was acceptable (auc > 0.5) with 77% sensitivity and 43% specificity in determined cutoff of 0.9µg/ml. lactoferrin is more accurate and sensitive than procalcitonin for diagnosis of acute appendicitis. sevgi et al. reported a good accuracy (auc=0.79) for lactoferrin between cases with uncomplicated appendicitis and nonappendicitis (13). our results showed that lactoferrin is less accurate than wbc, neutrophil and alvarado score. in our study, both wbc and alvarado score had better accuracy, specificity and sensitivity as well. alvarado score with the cut-off of 7 points has the highest sensitivity (95%) while the specificity was just 22%. it has been shown that the sensitivity and specificity of the alvarado score vary, ranging from 60% to 80% in different studies (23-26). apparently, alvarado score has more benefits than biomarkers, because whenever the patient’s condition alters, this scoring system can be evaluated more rapidly, repeatedly and easily. nevertheless, the combination of both alvarado score and biomarkers such as pct and lf will be more accurate in diagnosis of patients with appendicitis in the emergency department. we could find a significant difference between serum level of lactoferrin and procalcitonin between our patients and healthy controls; however, the measured parameters did not have any correlation with each other. neutrophil and wbc count seem to be better diagnostic markers for acute appendicitis compared to lactoferrin and procalcitonin. procalcitonin and lactoferrin might have the potential to be used in a panel with wbc and crp in order to decrease the number of false positive and false negative cases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e51 5. limitation it should be noted that the result of the present study has been obtained in light of some limitations. first, we had a small sample size and it did not allow us to make any generalization. second, the measurement of those parameters is expensive and takes a few hours, which may be an important time period in the emergency department. third, the cut-off value presented in our study may not work as well in another study with a different case mix. lastly, procalcitonin may not increase significantly until 8–12 h. therefore, for patients admitted early to the emergency department, serum pct may not indicate the clinical severity. 6. conclusion based on the main finding of present study, the overall accuracy of serum pct and lf in detection of patients with acute appendicitis are in poor to failed range and it seems that they could not be considered as good screening tools for this propose. 7. appendix 7.1. acknowledgements we are thankful to all volunteers who participated in this study. we also acknowledge the financial support of the research council of mashhad university of medical sciences for this project. 7.2. authors’ contribution all the authors participated in the research design and contributed to different sections of the research. the project was performed by anvar soleimani. statistical analyses were performed by arash soltani. management of the project and revision of the manuscript were performed by mohammadreza motie and seyed isaac hashemy. 7.3. funding/support this project was supported by the research council of mashhad university of medical sciences (grant number: 900647). 7.4. conflict of interest there is no competing interest to declare in this manuscript. references 1. addiss dg, shaffer n, fowler bs, tauxe rv. the epidemiology of appendicitis and appendectomy in the united states. am j epidemiol. 1990;132(5):910-25. 2. schellekens dh, hulsewe kw, van acker ba, van bijnen aa, de jaegere tm, sastrowijoto sh, et al. evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis. acad emerg med. 2013;20(7):703-10. 3. smink ds, finkelstein ja, garcia pena bm, shannon mw, taylor ga, fishman sj. diagnosis of acute appendicitis in children using a clinical practice guideline. j pediatr surg. 2004;39(3):458-63. 4. flum dr, morris a, koepsell t, dellinger e. has misdiagnosis of appendicitis decreased over time? a populationbased analysis. jama. 2001;286(14):1748-53. 5. humes dj, simpson j. clinical presentation of acute appendicitis: clinical signs–laboratory findings–clinical scores, alvarado score and derivate scores. in: keyzer c, gevenois pa, editors. imaging of acute appendicitis in adults and children. berlin, heidelberg: springer berlin heidelberg; 2012. p. 13-21. 6. mostbeck g, adam ej, nielsen mb, claudon m, clevert d, nicolau c, et al. how to diagnose acute appendicitis: ultrasound first. insights imaging. 2016;7(2):255-63. 7. petroianu a. diagnosis of acute appendicitis. int j surg. 2012;10(3):115-9. 8. yu cw, juan li, wu mh, shen cj, wu jy, lee cc. systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, c-reactive protein and white blood cell count for suspected acute appendicitis. br j surg. 2013;100(3):322-9. 9. thuijls g, derikx jp, prakken fj, huisman b, van bijnen ing aa, van heurn el, et al. a pilot study on potential new plasma markers for diagnosis of acute appendicitis. am j emerg med. 2011;29(3):256-60. 10. al-nawas b, krammer i, shah pm. procalcitonin in diagnosis of severe infections. eur j med res. 1996;1(7):331-3. 11. chandel v, batt sh, bhat my, kawoosa nu, yousuf a, zargar br. procalcitonin as the biomarker of inflammation in diagnosis of appendicitis in pediatric patients and prevention of unnecessary appendectomies. indian j surg. 2011;73(2):136-41. 12. yamashita h, yuasa n, takeuchi e, goto y, miyake h, miyata k, et al. diagnostic value of procalcitonin for acute complicated appendicitis. nagoya j med sci. 2016;78(1):79-88. 13. sarsu sb, erbagci ab, ulusal h, karakus sc, bulbul og. the place of calprotectin, lactoferrin, and high-mobility group box 1 protein on diagnosis of acute appendicitis with children. indian j surg. 2017;79(2):131-6. 14. green i, kirkpatrick ch, dale dc. lactoferrin–specific localization in the nuclei of human polymorphonuclear neutrophilic leukocytes. proc soc exp biol med. 1971;137(4):1311-7. 15. langhorst j, elsenbruch s, koelzer j, rueffer a, michalsen a, dobos gj. noninvasive markers in the assessment of 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procalcitonin in patients with suspected appendicitis. world j surg. 2012;36(8):1744-9. 21. kafetzis da, velissariou im, nikolaides p, sklavos m, maktabi m, spyridis g, et al. procalcitonin as a predictor of severe appendicitis in children. eur j clin microbiol infect dis. 2005;24(7):484-7. 22. khan an, sawan a, likourezos a, schnellinger m, garcia e. the usefulness of procalcitonin in the diagnosis of appendicitis in children: a pilot study. emerg med int. 2012;2012:317504. 23. bundy dg, byerley js, liles e, perrin em, katznelson j, rice he. does this child have appendicitis? jama. 2007;298(4):438-51. 24. b. are. meta-analysis of the clinical and laboratory diagnosis of appendicitis. bjs. 2004;91(1):28-37. 25. abdeldaim y, mahmood s, mc avinchey d. the alvarado score as a tool for diagnosis of acute appendicitis. irish medical journal. 2007;100(1):342. 26. wu j-y, chen h-c, lee s-h, chan r-c, lee c-c, chang ss. diagnostic role of procalcitonin in patients with suspected appendicitis. world j surg. 2012;36(8):1744-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e77 or i g i n a l re s e a rc h implementation of the health system reform plan in hospital emergencies of iran; a qualitative study shahriar janbazi1, ayad bahadorimonfared2∗, mostafa rezaei-tavirani3, ali maher4, mojtaba zonoobi5, naser vazifehshenas6, khatereh hanani7 1. faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of health & community medicine, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. 3. proteomics research center, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 4. department of health policy, economics & management, school of management and medical education, shahid beheshti university of medical sciences, tehran, iran. 5. information technology unit, shahid beheshti university of medical sciences, tehran, iran. 6. resource management, central library & archives, shahid beheshti university of medical sciences, tehran, iran. 7. statistics & information technology management, shahid beheshti university of medical sciences, tehran, iran. received: august 2020; accepted: august 2020; published online: 23 september 2020 abstract: introduction: health and efforts to maintain and promote it have always been an essential priority in various countries. this study aims to evaluate the implementation of the health system reform plan in emergency departments in iran. methods: this qualitative study evaluated five dimensions (finance, social responsibility, growth and learning, service recipients, and internal processes) through examining 70 indicators in 400 healthcare service providers and 300 healthcare recipients after the implementation of reform plan in ten emergency departments affiliated to shahid beheshti university of medical sciences using the balanced scorecard based on comprehensive evaluation model for the health system reform plan in iran (cehsrp-ir), from 2018 to 2019. results: from the perspective of 51% of service providers and 55% of service recipients, the health system reform plan has achieved its goals in hospital emergencies. significant gap between the ideal effectiveness and the current situation in health services in hospital emergencies was observed, especially in the educational and financial dimension. conclusion: according to the findings of this study, adaptation of activities and programs to the model proposed for emergency departments in health reform plan is essential for improving its effectiveness. keywords: health care reform; health policy; emergency service, hospital; outcome assessment, health care; health plan implementation cite this article as: janbazi sh, bahadorimonfared a, rezaei-tavirani m, maher a, zonoobi m, vazifehshenas n, hanani kh. implementation of the health system reform plan in hospital emergencies of iran; a qualitative study. arch acad emerg med. 2020; 8(1): e77. 1. introduction the ministry of health and medical education of iran has proposed a plan to reform the health system with eight executive packages aimed at reducing the payment of hospitalized patients in public hospitals, supporting the physi∗corresponding author: ayad bahadorimonfared address: department of health & community medicine, faculty of medicine, shahid beheshti university of medical sciences, tehran, iran. tel: 00989122151854, email: a.bahadori@sbmu.ac.ir. cians to stay in deprived areas, planning for specialist physicians to be present in public hospitals, improving the quality of hoteling in public hospitals, promoting natural childbirth program, and providing financial protection for incurable unique diseases, and patients in need since 05/05/2013. the next phase of this plan started after a while in the field of health (1). today, patient’s satisfaction with the treatment sector is recognized as a critical indicator of the efficiency of the corresponding organization (2). on the other hand, patient satisfaction is an essential indicator of emergency care quality (3). patient satisfaction can be defined as the recipient’s response this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. janbazi et al. 2 to the services provided, which reflects his or her overall understanding of the quality of service provided (4). how the service is provided in this ward can reflect the general state of service delivery throughout the hospital. in general, due to the emergency unit’s importance, increasing satisfaction in this ward has a significant effect on people’s attitudes towards the hospital (5). with the introduction of new management concepts to the medical world, today, emergency departments are concerned with patient satisfaction and rights more than ever. in contrast, the emergency department faces more challenges compared to other parts of the hospital, which can reduce patient satisfaction (6). the quality of service is crucial in evaluating the health sector, especially hospitals, and to evaluate it accurately and effectively, a "scientific standard and model" is needed to compare quantitative and qualitative performance with standards so that we can find out how the situation is and take action to solve its problems. due to the need for quantitative and qualitative improvement of services in the hospital emergency department, this area is of particular importance and requires proper knowledge (7). in an applied study, a comprehensive model was designed to evaluate the health system transformation plan in iran. the feature distinguishing this study from previous studies is the simultaneous attention to performance appraisal challenges, social responsibilities, and study in a comprehensive and coherent manner. the 900-balanced scorecard based on comprehensive evaluation model of the health system reform plan in iran is based on five dimensions (finance, social responsibility, growth and learning, clients, and internal processes), 17 components, and 70 indicators. this comprehensive model is called cehsrp-ir for short. it has a comprehensive approach in four levels (policymakers and strategic managers, resource providers, service providers, and service recipients) and uses qualitative and quantitative research methods (e.g., content analysis, pairwise comparisons, delphi method), and is an accurate tool for practical evaluation of the health reform plan (figure 1). this study aimed to evaluate the implementation of the health system reform plan in emergency departments in iran using the mentioned tool. 2. methods 2.1. study design and setting this is a qualitative study conducted in 2018-2019. the health system transformation plan was evaluated in ten emergency departments of hospitals (educational and noneducational) affiliated to shahid beheshti university of medical sciences using the comprehensive evaluation model of the health system reform plan in iran (cehsrp-ir). five educational hospitals (including imam hossein, loghman hakim, shohadaye tajrish, modarres, and taleghani) and five non-educational hospitals (including imam khomeini of firoozkooh, sevvom-e-shaban of damavand, shohadaye gomnam, zaeem pakdasht, and shohadaye pakdasht) were studied. in all stages of collecting and analyzing the data of this research, ethical considerations, observance of data integrity, and confidentiality of the participants’ opinions in the evaluation have been observed. besides, this study has been approved by the national ethics committee with the ethics code of ir.sbmu.retech.rec.1397.1394, to observe ethical considerations and confidentiality. the present study was conducted based on a matrix that includes five dimensions (learning and growth, internal processes, finance, clients, social responsibilities), four levels (service providers, service recipients, resource providers, and managers), 70 indicators, and 900-balanced scorecard model. in this model, the center with the highest score has been the most effective in achieving the goals defined in the five dimensions and, ultimately, the best efficiency in implementing the health system reform plan. in this study, based on the sample size calculated using cochran’s formula, 400 staff members from the emergency departments of the ten hospitals were randomly selected for evaluating the implementation of the health system reform plan. this study’s practical purpose was to use the cehsrp-ir model to evaluate the ten emergency departments in terms of adherence to the health system reform plan. in addition, the viewpoint of emergency service recipients (patients) regarding the implementation of the health reform plan was evaluated in two hospitals, which had the highest and lowest evaluation scores in the first phase, using this model. shahid beheshti university of medical sciences, covers about 52% of tehran’s population, which was selected to implement the health system reform plan. the population covered by this university alone is more than 19 provinces of the country, such as golestan, yazd, hamedan, qazvin, qom, and kermanshah (8). 2.2. participants the participants of the study, which was performed in two phases, consisted of the treatment staff (service provider) and patients who referred to the emergency departments of the studied hospitals. in the first phase, the sample size was estimated as 400 participants, and in the second phase, it was estimated as 300 participants using cochran’s formula. in the first phase, the samples were selected via target stratified random sampling and in the second phase using a simple random sample. 2.3. data gathering and analysis the effectiveness of the emergency department of the studied hospitals was measured from the perspectives of both this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e77 the service providers and the service recipients using a standard questionnaire that was designed based on the model (cehsrp-ir), and its validity and reliability were confirmed. second-order confirmatory factor analysis has been used to confirm this model. therefore, smart pls software was used to perform this analysis. according to the analysis outputs, all obtained factors’ load coefficients were greater than 0.4. also, cronbach’s alpha and reliability in this model were higher than 0.7. then, to measure the composite reliability, the cr (composite reliability) statistic was examined, which was higher than 0.7. this indicates the proper fit of the model. significance coefficients of z were examined to measure the good-fitting structural model, the value of which was more than 1.96 for all obtained coefficients, and shows the significance of all questions and relationships between variables with 95% confidence level. in the r squares criterion, all values related to the endogenous variables of the model were greater than 0.4, which shows a strong fit of the structural model. data were then analyzed using software including the office version, 2019 and spss version, 2017, and specialized cehsrp-ir software (ver2). 3. results 3.1. evaluation from the perspective of service providers in this phase, the standard questionnaire consisting of 70 items from the indicators in the model (cehsrp-ir), was given to 400 emergency staff from five educational hospitals (including imam hossein, loghman hakim, shohadaye tajrish, modarres, and taleghani) and five non-educational hospitals (including imam khomeini of firoozkooh, sevvome shaban of damavand, shohadaye gomnam, zaeem pakdasht, and shohadaye pakdasht). results are presented below: 3.1.1 general evaluation the function of the evaluation model used in this study, which rates the effectiveness of the performance of health service providers based on their score, is to identify their strengths and weaknesses in a general and specialized way (separately for the five dimensions of the model). first, a general evaluation of the performance of the studied hospital emergencies was performed, the results of which are as follows: based on the evaluation on the 900-balanced scorecard model (cehsrp-ir), the emergency department of shahid modarres hospital ranked first in implementation of the health system reform plan with 554.38 points and zaeem pakdasht hospital with 364.17 points ranked last (tenth) (table 1). findings of this stage showed that the emergency department of shahid modarres hospital, despite being 345.62 points away from the ideal point of effectiveness of the health system, had the highest rank among the ten centers studied. its difference with zaeem pakdasht hospital, which was at the bottom of the ranking of this study, is a positive distance of 190.21 points. 3.2. evaluation of five dimensions as shown in table 1, the rankings of the studied hospital emergency departments in each dimension were determined based on the comprehensive evaluation model. therefore, each hospital’s emergency department must eliminate its weaknesses to improve the services provided to the people in the health reform plan. using the analysis provided by the relevant software, the details of the points and strengths and weaknesses of each dimension can be seen in each center, and they lay grounds for plans to eliminate the shortcomings and effectively implement the health system reform plan. 3.2.1 evaluation of growth and learning according to the assessment made in the growth and learning dimension of the health system reform plan in the emergency room of the ten studied hospitals (table 1), shahid modarres hospital with a score of 135.18 and taleghani hospital with a score of 98.4, and sevvom shaban hospital in damavand with a score of 98.2 have the lowest ranks. it is important to note that taleghani hospital is an educational hospital, but has received a low score (98/4) in the evaluation, so it is recommended to pay special attention to strengthening the indicators of growth and learning in this hospital. 3.2.2. evaluation of social responsibilities according to the evaluation made in the social responsibility dimension of the health system reform plan in the emergency departments of the ten studied hospitals, as shown in table 1, shahid modarres hospital with a score of 136.97 ranked first and zaeem hospital in pakdasht ranked last with a score of 82.93. therefore, it is suggested to pay more attention to the social responsibilities that have a special place in the health system reform plan and its indicators in the hospitals that have not obtained the desired score. 3.2.3. evaluation of internal processes according to the results of the evaluation of the internal processes of the health system reform plan in the emergencies of the ten studied hospitals, as shown in table 1, shahid modarres hospital with a score of 56.09 and sevvom-eshaban hospital in damavand with a score of 38.03 ranked first and last, respectively. therefore, it is suggested that efforts be made to eliminate the shortcomings of internal processes and to modify and shorten the processes and eliminate redundant processes to improve the effectiveness of the health reform plan. 3.2.4. assessments of clients the evaluation of the clients (patients) of the health system reform plan in the emergency departments of the 10 studied hospitals is shown in table 1, shahid modarres hospital, with 97.05 and zaeem hospital in pakdasht with a score of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. janbazi et al. 4 table 1: ranking of emergency departments of shahid beheshti university of medical sciences based on the scores of health reform plan evaluation dimensions hospitals evaluation dimensions total score growth&learning social responsibility internal processes clients financial shahid modarres 135.8 136.97 56.9 97.05 144.92 554.38 imam hossein 120.8 131.4 49.73 81.3 156.88 524.8 loghman hakim 131.4 129.57 54.1 80.88 117.93 495.17 shohadaye pakdasht 125.02 112.9 52.45 88.6 109.45 472.4 imam khomeini* 114.55 116.72 48.67 86.33 121.1 471.38 shohadaye gomnam 117.75 110.5 47.1 82.08 124.43 466.13 shohadaye tajrish 115.42 121.37 47.15 77.1 110.25 456.15 sevvome shaban** 98.2 106.27 38.03 73.63 109.95 413.12 taleghani 98.4 102.48 41.3 74.2 100.28 404.43 zaeem pakdasht 101.13 82.93 39.9 66.57 86.8 364.17 *firoozkooh; ** damvand. figure 1: comprehensive evaluation model for health system reform plan in iran ( janbazi et al., (13); this figure is used with permission). 66.57 points ranked first and tenth, respectively. therefore, it is suggested to attempt to improve the desired indicators in the client dimension to increase effectiveness and client satisfaction. 3.2.5 evaluation of financial dimension according to the evaluation of the health system reform plan’s financial dimension in the emergency departments of the ten studied hospitals, as shown in table 1, imam hossein hospital with a score of 158.88 and zaeem hospital in pakdasht with a score of 86.08 are ranked first and tenth, respectively. it is suggested to plan to improve the desired indicators in the financial dimension to enhance the effectiveness of the health reform plan. studies show that since imam hossein hospital was the first hospital in the experimental establishment of the financial system related to the health system reform plan in the country, it has had more experience, knowledge, and acceptable growth in this model dimension. 3.3. evaluation from the perspective of service recipients according to the findings of this study in the previous section, it was decided to evaluate the health system reform plan in two hospitals of shahid modarres with a capacity of 370 beds and zaeem hospital in pakdasht with a capacity of 120 beds, which had obtained the highest and lowest scores in the first phase of evaluation. in this phase, data were collected and analyzed using the opinions of 300 service recipients and using the standard questionnaire. the findings of this section show that 51% of the studied patients were satisfied with the hospital emergency services in providing health this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e77 services. in this dimension, which has 160 points, modares hospital, with a score of 107.88, achieved the satisfaction of 67.50% of the clients. with a score of 55.90, zaeem hospital has not been able to keep more than 35% of the service recipients satisfied. 4. discussion the study’s findings revealed that despite the high volume of work and increasing services provided to patients, the studied emergency departments still have a long way to reach the ideal point regarding the effectiveness of services from the viewpoint of the target community. the acquired score of the studied hospitals in the form of the comprehensive evaluation model used, especially, the average score obtained in the evaluation phase of service recipients’ feedback, which indicates 55% satisfaction, indicates the need to review the health system reform plan. emergency service, as the first line for dealing with patients, provides medical services that can be presented in the form of a health reform plan. on the other hand, very little research has been done to evaluate iran’s health reform plan. therefore, this research has the advantage that has evaluated the services provided in sbmu, the largest community providing healthcare based on the health system reform plan. a study conducted by dehghan et al. (2016) intended to examine the performance of the health system reform plan from the perspective of yazd university hospital executives, 47.2% of managers stated that the health system reform plan had achieved 60 to 79% of their goals. also, 49.1% of managers believed that the health system’s reform plan has been able to achieve a lot in dealing with out-of-tariff costs. another belief of managers was that patients are more satisfied with the health system reform plan than doctors and nurses (9). however, the results of the present study do not match the findings of dehghan et al., because the evaluation score of the reform plan in this study in the best hospital (modarres) shows 61.6% success and in the worst evaluation score (zaeem pakdasht) is 40.46%. besides, the evaluation results from patients’ point of view, is not in agreement with the research findings of dehghan et al.. it seems that four years after the implementation of the plan, the occurrence of defects and possible disruptions is one of the reasons for the decrease in inpatient and service providers’ satisfaction. in a study conducted by goodarzi et al. (2015), they concluded that patients were more satisfied with the health system reform plan than the medical and treatment staff. conversely, nursing and support staff have been most dissatisfied with the health system reform plan. on the other hand, the satisfaction of health care service providers encourages hospital managers to the continue the medical services provided and their commitment, and the dissatisfaction of managers and employees has undesirable consequences on the plan. the dissatisfaction of managers and medical staff leads to their disconnection from the health care system or at least their non-participation in the provision of services (10). therefore, the findings of this study showing the increase of dissatisfaction among both staff and patients with the health reform plan are inconsistent with the results of goodarzi et al.’s research. in a study conducted by sinaki et al. (2015), which analyzed job satisfaction of medical staff after the implementation of the health system reform plan in kosar hospital in qazvin, the results showed that the overall job satisfaction of the majority of medical staff was at a moderate level (11). the findings of this study are consistent with the findings of sinaki et al. in a study conducted by wu et al. (2019) in which 216 professional staff rated the importance of the main views of the balanced scorecard, the ranks were as follows: patient, internal process, learning and growth, and finances. the weightbased analysis highlighted the importance of all indicators and areas that needed serious attention in future planning and management. this study recommended creating a balanced scorecard measurement system for integrated care organizations in china (12). the present study considered social responsibility in addition to the other dimensions addressed in in wu’s research. regarding the prioritization of dimensions, the present study differs from wu’s research. based on the results of this research, in the learning and growth dimension, using health data in line with research goals and unraveling the country’s health problems, reforming the educational system based on the country’s health map, expanding creativity, innovation and technology in the field of health, and comprehensive knowledge management in all levels of the health transformation plan had the most significant weight and impact on the effectiveness of the plan and its outcome in hospital emergency services, respectively. according to the results of this research, in social responsibilities dimension, system establishment and participation of all groups involved in the health reform plan to actively monitor the implementation of the plan, full development of services including insurance and health services in all parts of the country for different social classes, the commitment of government agencies to comprehensively implementing the plan, and paying attention to the fundamental rights of the people had the most significant weight and impact on the effectiveness of performance and plan outcome, respectively. based on the results of this research, in internal processes dimension, eliminating interference chains in the service path, especially emergencies, development of standard protocols, and use of intelligent systems, attracting the participation of institutions and organizations at the international, regional, national and local levels had the highest weight and impact on the effectiveness of the project, respectively. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. janbazi et al. 6 according to the results of this research, in the financial dimension, intelligent and purposeful monitoring of supply, distribution and consumption of equipment and pharmaceutical and medical supplies, financing of the plan from public and charitable budgets, progress and effectiveness, and optimizing income, payments and investment based on service levels had the most significant weight and impact on the effectiveness of performance and outcome of the plan, respectively. based on the results of this study, in the service recipient dimension, maximum satisfaction of project clients, community health growth and disease management, and creating transparency platforms had the highest weight and impact on the effectiveness of the plan and outcome of the design, respectively. 5. limitations in conducting this study, there were no limitations. 6. conclusion analysis of the results of this study and the average of study measurements showed that the health system reform plan has reached its goals from the perspective of 51% of service providers and 55% of service recipients in the emergency services of the studied hospitals. these results, together with the ranking result of the studied centers, indicate a significant distance between the effectiveness of the health system reform plan and the ideals in the evaluation model. this is consistent with the findings of most health researchers in iran; thus, highlighting the significant gap between the results and the objectives of the project, which indicates the need for reevaluating this national program. a huge amount of financial and human resources of the country has been spent on this program, but its efficiency has only been about 50%. 7. declarations 7.1. acknowledgements we would like to thank all the university professors, researchers; statistics and information technology engineers; and those who helped us with this research, as well as all of the staff of shahid beheshti university of medical sciences who supported us. 7.2. author contribution all authors contributed in designing, running, and writing all parts of the research. 7.3. funding/support funds have been received from vice-chancellor in research affairs of sbmu for doing this project. 7.4. conflict of interest the authors declare no conflict of interest. references 1. emami razavi sh. health system reform plan in iran: approaching universal health coverage. hakim research journal. 2016;18(4):329-35. 2. abd manaf nh, mohd d, abdullah k. development and validation of patient satisfaction instrument. leadership in health services. 2012. 3. boudreaux ed, mandry cv, wood k. patient satisfaction data as a quality indicator: a tale of two emergency departments. academic emergency medicine. 2003;10(3):261-8. 4. mckinley r, roberts c. patient satisfaction with out of hours primary medical care. bmj quality & safety. 2001;10(1):23-8. 5. taylor c, benger jr. patient satisfaction in emergency medicine. emergency medicine journal. 2004;21(5):52832. 6. lau fl. can communication skills workshops for emergency department doctors improve patient satisfaction? emergency medicine journal. 2000;17(4):251-3. 7. vahidi a, arzemani m, jafakesh moghadam a, vahidi m, hashemi m. investigation into performance of emergency units of hospitals of north khorasan university of medical sciences in 2012. journal of north khorasan university of medical sciences. 2013;5(1):159-65. 8. aghajani m. satisfaction of iranians with health reform plan. jamjam news. 2015. 9. dehghan a, mirjalili mr, zare mehrjardi mh, maliheh r, samiyezargar a, kazemeini sk. performance of health care system reform plan from the perspective of university hospitals executives in yazd province in 2015. management strategies in health system. 2016;1(1):43-9. 10. goodarzi l, khairi f, meshkini a, khaki a. the satisfaction of the patients and the treatment staff from the implementation of the health system reform plan. proceedings of the national exhibition of performance criticism of the eleventh government in the field of health; tehran: national institute of health; 2015. p. 43-4. 11. sinaki s, rajabi g, rezaee n. assessing physicians awareness of the reform of the health system in iran. proceedings of the national exhibition of performance critthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e77 icism of the eleventh government in the field of health; tehran: national institute of health; 2015. p. 36-7. 12. wu x, li s, xu n, wu d, zhang x. establishing a balanced scorecard measurement system for integrated care organizations in china. the international journal of health planning and management. 2019;34(2):672-92. 13. mandejin mrr, eslambulchi a. strategy mapping and introducing the health system reform plan: an iranian social responsibility-based approach. social determinants of health. 2019;5(3):177-90. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2018; 6 (1): e34 ca s e re p o rt anaphylaxis as a rare side effect of pantoprazole; a case report gholamreza faridaalaee1, javad ahmadian heris2,3∗ 1. department of emergency medicine, maragheh university of medical sciences, maragheh, iran. 2. department of allergy and clinical immunology, pediatric hospital, tabriz university of medical sciences, tabriz, iran. 3. department of allergy and clinical immunology, rasool-e-akram hospital, iran university of medical sciences, tehran, iran. received: february 2018; accepted: april 2018; published online: 21 may 2018 abstract: anaphylaxis is a serious life-threatening allergic reaction. any medication may potentially trigger anaphylaxis, but reaction to pantoprazole is rare. our case is a 21 year-old girl with anaphylactic reaction to pantoprazole a short time after prescription. keywords: pantoprazole; anaphylaxis; proton pump inhibitors; hypersensitivity © copyright (2018) shahid beheshti university of medical sciences cite this article as: faridaalaee gh, ahmadian heris j. anaphylaxis as a rare side effect of pantoprazole; a case report. emergency. 2018; 6 (1): e34. 1. introduction pantoprazole is one of the proton pump inhibitor agents, which was first introduced in 1994. pantoprazole and other proton pump inhibitors (ppis) reduce acid production and its indications are treatment of erosive gastritis, esophagitis, gastric ulcer, duodenal ulcer and zollinger ellison syndrome (1). many side effects have been reported following pantoprazol usage but it has rarely been reported as a cause of anaphylaxis. here, we present a case of anaphylactic reaction to intravenous pantoprazole in a young woman who had presented to emergency department following epigastric pain. 2. case presentation: the case is a 21-year-old woman who was brought to emegency department of amiralmomenin hospital, maragheh, iran, with epigastric pain, which had started 2 days before. the pain was localized, did not radiated to anywhere, and was slightly relived with eating and exacerbated after half an hour. she did not have bloody vomit or melena. she had loose defecation three times a day. vital signs were as follow: blood pressure = 80/120 mmhg, heart rate = 72 beat/minute, respiratory rate = 14 beat/minute, and arterial ∗corresponding author: javad ahmadian heris; department of allergy and clinical immunology, pediatric hospital, vahidi street, tabriz, iran. email: jahmadian76@yahoo.com tel: 009841 35262280 oxygen saturation =94% in room air. after careful history taking and clinical examination, the patient was diagnosed as gastritis. intravenous line was accessed and she was treated with 40 mg intravenous pantoprazole. 2 minutes after drug administration, the patient was symptomatic with hives, dyspnea and cyanosis and her blood pressure had decreased to 85/60 mmhg, heart rate increased to 101/minute, and oxygen saturation to 78% in room air. she was immediately treated as anaphylactic shock with normal saline (30cc/kg), intramuscular epinephrine (0.3 mg), interavenous hydrocortisone (100 mg) and chlorpheniramin (4 mg). 6 lit/minute oxygen was administered via an oxygen mask. gradually, her general condition improved and after 2 hours, the general condition completely was recovered. she was discharged after 12 hours. 3. discussion several complications such as headache, dizziness, joint pain, nausea, vomiting, abdominal pain, increased risk of stomach and pancreatic cancer, acute interstitial nephritis, diarrhea, risk of fractures, vitamin b 12 deficiency, hypomagnesaemia, fever, hypertensive pneumonitis, liver damage, severe acute hepatitis, kounis syndrome and thrombocytopenia have been reported following usage of ppis (1-10). acute and delayed allergic reactions and systemic reactions have been reported in rare cases, even with oral doses of pump inhibitor drugs (11-14). there are occasional cross-reactions this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com gh. faridaalaee & j. ahmadian heris 2 between different drugs in this group (14). our search in literature shows that a few cases of anaphylaxis to ppi have been reported (14-16), and our case is another report of anaphylaxis to pantoprazole. anaphylatic reaction to ppis is reported with both oral and iv routes of administration (17, 18). hou-chuan lai et al. presented a case of anaphylaxis to iv pantoprazole in a 50 year-old male patient during general anesthesia, who was discharged after successful resuscitation (19). v. vovolis et al. in a study in 2008 showed that skin test with ppis could be considered as an accurate and simple method of evaluating the cross reaction between drugs of this group (20). anaphylactic reaction to ppis is rare but, like other causes of anaphylactic shock, it is life treatining. it seems that emergency phycisians should be aware of this problem and take care of the patients in case of this reaction happening. 3.1. discussion the patient gave us informed consent to publish this presentation. 4. appendix 4.1. acknowledgements all the staff members of the emergency department of imam hospital are thanked for their cooperation throughout the study period. 4.2. authors contribution all authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 4.3. conflict of interest the authors declare that there is no conflict of interest. 4.4. funding and support none. references 1. richardson p, hawkey cj, stack wa. proton pump inhibitors. pharmacology and rationale for use in gastrointestinal disorders. drugs. 1998;56(3):307-35. 2. atkins c, maheswaran t, rushbrook s, kamath a. lansoprazole-induced acute lung and liver injury: a case report. international journal of clinical pharmacology and therapeutics. 2014;52(12):1102-4. 3. binnetoglu e, akbal e, sen h, gunes f, erbag g, asik m, et al. pantoprazole-induced thrombocytopenia in patients with upper gastrointestinal bleeding. platelets. 2015;26(1):10-2. 4. canpolat u, sahiner l, aytemir k, oto a. allergic reaction to proton pump inhibitor: pantoprazole induced kounis syndrome. international journal of cardiology. 2012;159(2):e27-8. 5. klassen s, krepinsky jc, prebtani ap. pantoprazoleinduced acute interstitial nephritis. cmaj : canadian medical association journal = journal de l’association medicale canadienne. 2013;185(1):56-9. 6. pirson f, geubel a, marot l. late hypersensitivity to omeprazole and other proton pump inhibitors. acta clinica belgica. 2012;67(4):301-3. 7. quasdorff m, mertens j, dinter j, steffen hm. recurrent hypomagnesemia with proton-pump inhibitor rechallenge. annals of internal medicine. 2011;155(6):405-7. 8. sandig c, flechtenmacher c, stremmel w, eisenbach c. pantoprazole induces severe acute hepatitis. zeitschrift fur gastroenterologie. 2011;49(2):207-10. 9. schiller d, maieron a, schofl r, donnerer j. drug fever due to a single dose of pantoprazole. pharmacology. 2014;94(1-2):78-9. 10. torlot fj, whitehead dj. acute interstitial nephritis caused by two different proton pump inhibitors. british journal of hospital medicine (london, england : 2005). 2016;77(1):50-1. 11. candar m, gunes h, boz bv, kandis h, kutlucan l, saritas a. asystole after the first dose of lansoprazole. the american journal of emergency medicine. 2014;32(10):1302. e3-. e4. 12. haeney m. angio-edema and urticaria associated with omeprazole. bmj: british medical journal. 1992;305(6858):870. 13. lamtha sc, allam rn, karthak c, bhutia kd. anaphylactic reaction to omeprazole. tropical gastroenterology : official journal of the digestive diseases foundation. 2015;36(2):136-7. 14. natsch s, vinks mh, voogt ak, mees eb, meyboom rh. anaphylactic reactions to proton-pump inhibitors. the annals of pharmacotherapy. 2000;34(4):474-6. 15. lai hc, hsu sw, lu ch, ma hi, cherng ch, hung nk, et al. anaphylaxis to pantoprazole during general anesthesia. journal of anesthesia. 2011;25(4):606-8. 16. nand n, dsouza s, batra n, chauhan v, yadav m. intravenous pantoprazole-induced near fatality. the journal of the association of physicians of india. 2015;63(6):96. 17. gonzalez p, soriano v, lopez p, niveiro e. anaphylaxis to proton pump inhibitors. allergologia et immunopathologia. 2002;30(6):342-3. 18. gratacos l, soy d, lluis m, lopez b, nicolas jm, codina c, et al. apparent anaphylaxis associated with pantoprazole. american journal of health-system pharmacy. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e34 2005;62(13):1388-9. 19. lai h-c, hsu s-w, lu c-h, ma h-i, cherng c-h, hung n-k, et al. anaphylaxis to pantoprazole during general anesthesia. journal of anesthesia. 2011;25(4):606-8. 20. vovolis v, koutsostathis n, stefanaki e. ige-mediated anaphylaxis to proton pump inhibitors–cross-reacting study. allergy. 2008;63(9):1251-2. 21. natsch s, vinks mh, voogt ak, mees eb, meyboom rh. anaphylactic reactions to proton-pump inhibitors. annals of pharmacotherapy. 2000;34(4):474-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction case presentation: discussion appendix references emergency. 2018; 6 (1): e32 le t t e r to ed i to r introducing a device for measuring pain intensity; a letter to editor keshvad hedayatyanfard1, shahin mohammad sadeghi2∗, iman habibi1 1. department of pharmacology, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 2. department of plastic and reconstructive surgery, shahid beheshti university of medical sciences, tehran, iran. received: november 2017; accepted: may 2018; published online: 17 may 2018 cite this article as: introducing a device for measuring pain intensity; a letter to editor. emergency. 2018; 6(1): e32. dear editor; pain is defined as an unpleasant feeling caused by a real or potential tissue injury and is classified into neuropathic, somatic and visceral types (1, 2). characteristics such as severity, location, duration and site of pain referral are very helpful in correct diagnosis and treatment of the disease. pain control in the emergency department is one of the first measures that should be taken for the patients and for this purpose, a wide range of analgesic drugs such as nsaids, opioids, and corticosteroids are used (3-5). for evaluating the success rate as well as determining the best medication required for controlling the patient’s pain, being aware of the pain severity is of great importance. therefore, a device or a method that can monitor pain severity and therefore, the process of patient treatment with high accuracy is very interesting. currently, various methods exist for assessing pain severity. one way is to ask the patient (self-report) for determining pain severity. among the most important methods based on self-report of the patient, numerical rating scales (nrs) and verbal rating scales (vrs) can be mentioned (6, 7). in cases that self-report by the patient is not possible, methods such as behavioral pain scale (bps) and critical care pain observation tool (cpot) can be used (8). one of the common methods for assessing pain severity and threshold in animal studies is using monofilaments (9, 10). these monofilaments are made from polyethylene and the base of their function is the bend that occurs at the time of applying pressure on the surface of the intended organ (figure 1). a wide range of these filaments is available, each of which apply a pre-determined force depending on the bend. ∗corresponding author: shahin mohammad sadeghi; department of plastic and reconstructive surgery, 15 khordad hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. box:1985717443, telfax: 09821 88902155 email:drshmsadeghi@gmail.com results of a study were indicative of 41% to 93% sensitivity and 68% to 100% specificity of monofilaments in determining pain threshold (10). however, temperature and humidity of the environment can affect the bending and therefore, the accuracy of the monofilaments (11). considering the afore-mentioned points, researchers of the present study attempted to design a digital device for assessing pain severity and threshold with characteristics such as accuracy, reproducibility, sensitivity, specificity, and ease of use. among the most important uses of this device, quantitative measurement of response to the external stimulant, pain threshold, and assessing the trend of response to treatment with various analgesic drugs can be pointed out. the device is made up of 2 parts of body and probe, the body includes an lcd with touch screen and internal memory for recording the performed tests. its accuracy in measurement is about 100 mg and it can show a maximum of 1000 g. the device can record the maximum force inflicted on the desired organ and can be connected to the computer and data can be printed out. in addition, the trend of force inflicted on the organ of the animal or human can be observed as a curve on the graph (figure 2). inside the probe there is a load cell with high sensitivity for measuring the inflicted force used and a there is also a steel rod, 1 mm in diameter, placed on the probe, which has a smooth cross section. this metal rod can be changed and various diameters can be used for animal and human study purposes. 1. method of using the device for evaluating the patient’s pain severity a force will be inflicted on the intended organ of the patient and when a pain equal to the original pain of the patient is felt and the patient responds to the performed stimulation and moves the intended organ, the maximum force is recorded. this test is performed 5 times and the mean inflicted force is recorded this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com k. hedayatyanfard et al. 2 figure 1: method of using monofilament in human. figure 2: a view of the digital device as pain severity. this device has been registered in the iranian office of intelthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e32 lectual and mental property under the number 87068. in addition, it has been chosen as the favorite invention in the festival of inventions of the iranian national elites foundation (in 2015). 2. appendix 2.1. acknowledgements the authors would like to thank ali ziai, feizolah nizai, behnam habibi, and farzad habibi for their contribution to the study. 2.2. author’s contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 2.3. conflict of interest none. 2.4. funding and support none. references 1. fink r, editor pain assessment: the cornerstone to optimal pain management. baylor university medical center proceedings; 2000: taylor & francis. 2. moayedi m, davis kd. theories of pain: from specificity to gate control. journal of neurophysiology. 2012;109(1):5-12. 3. rosenblum a, marsch la, joseph h, portenoy rk. opioids and the treatment of chronic pain: controversies, current status, and future directions. experimental and clinical psychopharmacology. 2008;16(5):405. 4. van laar m, pergolizzi jr jv, mellinghoff h-u, merchante im, nalamachu s, o’brien j, et al. pain treatment in arthritis-related pain: beyond nsaids. the open rheumatology journal. 2012;6:320. 5. vyvey m. steroids as pain relief adjuvants. canadian family physician. 2010;56(12):1295-7. 6. nippert ar. the expression of chronic pain: a multimodal analysis of chronic pain patients. 2015. 7. hui d, bruera e. a personalized approach to assessing and managing pain in patients with cancer. journal of clinical oncology. 2014;32(16):1640. 8. suzuki t. does the combination use of two pain assessment tools have a synergistic effect? journal of intensive care. 2017;5(1):1. 9. booth j, young mj. differences in the performance of commercially available 10-g monofilaments. diabetes care. 2000;23(7):984-8. 10. dros j, wewerinke a, bindels pj, van weert hc. accuracy of monofilament testing to diagnose peripheral neuropathy: a systematic review. the annals of family medicine. 2009;7(6):555-8. 11. haloua mh, sierevelt i, theuvenet wj. semmesweinstein monofilaments: influence of temperature, humidity, and age. journal of hand surgery. 2011;36(7):1191-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com method of using the device appendix references emergency. 2018; 6 (1): e26 or i g i n a l re s e a rc h prehospital emergency medical services challenges in disaster; a qualitative study mohamad sorani1, sogand tourani2∗, hamid reza khankeh3,4, sirous panahi5 1. department of health in emergencies and disasters, school of health management and information sciences, iran university of medical sciences, tehran, iran. 2. department of health services management, school of health management and information sciences, iran university of medical sciences, tehran, iran. 3. university of social welfare and rehabilitation sciences, tehran, iran. 4. department of clinical science and education, karolinska institute, stockholm, sweden. 5. department of medical library and information science, school of health management and information sciences, iran university of medical sciences, tehran, iran. received: february 2018; accepted: april 2018; published online: 26 april 2018 abstract: introduction: prehospital emergency medical care (emc) is a critical service in disaster management. the aim of this study was to explore the challenges of prehospital emergency medical services (ems) during disaster response in iran. methods: a qualitative study was conducted from april 2015 to march 2017. data were collected through in-depth, semi-structured interviews with 23 experienced individuals in the field of disaster that were selected using purposeful sampling. data were analyzed using content analysis approach. results: fifteen subthemes and the following six themes emerged in the analysis: challenges related to people, challenges related to infrastructure, challenges related to information management systems, challenges related to staff, challenges related to managerial issues and challenges related to medical care. conclusion: iran’s prehospital ems has been chaotic in past disasters. improvement of this process needs infrastructure reform, planning, staff training and public education. keywords: disaster planning; emergency medical services; qualitative research; earthquakes © copyright (2018) shahid beheshti university of medical sciences cite this article as: sorani m, tourani s, khankeh h, panahi s. prehospital emergency medical services challenges in disaster; a qualitative study. emergency. 2018; 6(1): e26. 1. introduction a ccording to the centre of research on the epidemiology of disasters (cred), disasters have become more frequent over the past decades (1). a wide range of health problems may result from disasters (2). usually, the number of deaths and injuries associated with disasters increases significantly in the first hours and days after the disaster strikes (3). ems is a critical component of the healthcare systems in these situations (4). the main goal of ems in disaster response is continuity of medical services through triage, life-saving support, rapid diagnosis and treatment, or ∗corresponding author: sogand tourani; number 6, yasemi st , kurdsistan ave, tehran, iran. tel: 0098-2188772086 – 989127544205 fax: 0098-2188772086 email: soga.tourani@gmail.com transfer of casualties to emergency departments (ed) (5). it has been shown that timely emergency medical care, especially in time-sensitive patients, improves outcomes (6). although a structured approach for ems response exists (7), reports of recent studies on disasters show that there is still much room for improvement (8, 9). it is observed that lack of appropriate preparedness and response plan can cause serious challenges for prehospital emergency medical services. in a worst-case scenario, ed may be physically damaged or may not be able to provide services due to the overcrowding by casualties (4). it is also shown that the prehospital ems may be disrupted due to resource limitations or road blockages (10). iran is a disaster-prone country. it is ranked as one of the world’s most at risk countries (11). three natural disasters with more than 10,000 deaths have occurred in iran from this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. sorani et al. 2 1990 to 2007 (12). annual average of 4000 reported deaths in iran have been attributed to disasters in the past decades (12). recently, iran’s healthcare system has focused on planning and preparing for disaster response, especially in the field of prehospital ems. however, to date, few empirical studies have been conducted to explore the dimensions of prehospital emergency medical services in disaster situations in iran. research on ems response to disaster can be used for policymaking or changing the method of practice. this study aimed to explore the challenges of prehospital emergency medical services during disaster response in iran. 2. methods 2.1. study design and setting this qualitative study was conducted from april 2015 to march 2017. guidelines provided by granheim were followed for applying content analysis (13). this is a suitable method when new areas are to be investigated in an explorative manner or if the area needs to be explored from a new perspective (14, 15). ethical clearance of the study was obtained from the research ethics review board of the iran university of medical sciences. verbal consent was obtained and all participants were informed that they could refuse to participate or withdraw from the interviews at any time. 2.2. participants purposeful sampling with maximum diversity was used to provide a realistic perspective concerning the ems response in disasters. the participants of the study consisted of twenty-three ems professionals; all had at least two prior disaster experiences in prehospital emergency care. the endpoint for sample selection was data saturation, meaning that further data collection failed to provide additional information or new codes were not developed. 2.3. data gathering data were collected using in-depth, semi-structured interviews with participants regarding the process of ems in the affected area. interviews with the participants started with their experience about emergency medical response to disaster, and according to the interview guidelines, general openended questions were asked, for instance “describe an instance when you participated in disaster response.” then, depending on the context of the responses, the interviewer continued with probe questions such as “could you explain more?” the time and location of the interviews were arranged by agreement with the participants. the interviews varied in length from 32 to 63 minutes. all interviews were conducted between april 2015 and february 2017. 2.4. data analysis qualitative content analysis was used concurrently with data gathering. recorded interviews were transcribed verbatim and verified by the participants. during the open coding phase, all the interviews were read several times for immersion, then line by line analysis began and primary codes were extracted. data were compared for similarities and differences, then labeled and grouped into categories and subcategories. finally, the underlying meanings were interpreted as themes . in accordance with the methodology of qualitative studies, data processing was performed by the same investigator for all interviews. 2.5. rigor trustworthiness of research was established through memos, prolonged engagement with data, constant comparison analysis, maximum variation of sampling, member checks, and peer checks. the findings and interpretations of the study were reviewed by the research team, which consisted of people with experiences in various fields such as disasters, emergencies, public health management and qualitative research. 3. results 23 people, including two nurses, four paramedics, three physicians, two dispatchers, five managers and seven experts in the field of disaster were studied. the participants ranged from 29 to 58 years of age with an average age of 39.23±9.1 years (78.3% male). prehospital emc challenges were classified under six main categories including challenges related to people, challenges related to infrastructure, challenges related to information management system, challenges related to staff, challenges related to managerial issues, and challenges related to medical care. 1. challenges related to people 1.1. inadequate knowledge about first aid laypeople do not have enough first aid knowledge and skills. their involvement may lead to more serious injuries. as one of the participants stated: “i saw many injured persons who could have had better physical conditions if laypeople did not intervene.” (p9) 1.2. crowd of people according to the participants, when disasters happen, many people from other regions move quickly to the affected area. overcrowding at disaster scene will slow down the relief, medical care and transfer of injured patients. there are also safety concerns due to the unstable environment. 2. challenges related to infrastructure this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e26 2.1. communication disruption immediately after disaster impact, communication within the affected area as well as outside the region are usually disrupted or jammed due to physical damage to the communication systems or high number of calls made. one of the national managers said that: “after the east azerbaijan earthquake in 2012, our communication with the affected area and even tabriz, which was not affected, was interrupted. there was no information from the affected area for up to 4 hours. we only knew that an earthquake has occurred. i had to go there by car to get information.” (p7) 2.2. difficult access usually, after disasters, there is heavy road traffic in the affected area and the surrounding area due to destruction of roads and streets, narrowness of the streets and overcrowding. this will disrupt the ems. one of the participants mentioned his experience: “after bam earthquake all roads were blocked for three days due to heavy traffic. the only way to perform relief operation was by aircraft.” (p6) 2.3. vulnerability of local health facilities one of the main health challenges in iran, as the participants stated, is the high vulnerability of health facilities to disaster. usually after a large or middle-scale disaster, local hospitals are severely damaged and unable to continue their normal daily functions. “in azerbaijan earthquake, the only local hospital, which had not even been officially opened yet, was unusable due to severe structural and non-structural damage.” (p13) 3. challenges related to information management system 3.1. lack of patient tracking system lack of patient tracking system was another challenge mentioned by the study participants. as experienced by the study participants, after the disaster, most casualties are transported to hospitals outside the affected area while there is no system for following up the identity, medical information and location of patients. “due to the lack of patient information systems, some families did not know the fate of their family members until several months after the incident and they were looking for them in hospitals in different cities.” (p17) 3.2. lack of integrated hospital information system there is no easy access to hospital information and capacity at local, regional and national level. this information can facilitate distribution of casualties. 4. challenges related to staff 4.1. inadequate skills in the field of disaster medical staff and even ems managers have inadequate knowledge and skills in disasters. “some staff did not know anything about simple triage and rapid treatment (start) algorithm.” (p6) 4.2. safety concerns the results of this study showed that, safety considerations are not a priority for the medical staff in the disaster response. also, there is not enough safety equipment available for stuff. one manager emphasized that: “most staff are trained about safety but they act heroically and emotionally in disaster field. they don’t take standard safety precautions, even in a situation that personal protective equipment is available.” (p4) 5. challenges related to managerial issues 5.1. unplanned response there is no operational plan for managing the evacuation process from the scene to local, regional or national medical centers. in disastrous events, ems system tries to transfer patients to the hospitals with daily protocol. this leads to congestion of patients, and dysfunction in eds. 5.2. limitation of aero medical service while there are numerous casualties, roads have been destroyed or there is a heavy road traffic, air evacuation is the most important system to transfer numerous casualties to the medical centers. the iranian medical air fleet is worn out and does not have enough equipment to evacuate numerous casualties. many cities in iran also have no airport or helicopter pad. one of the participants mentioned his experience: “the great bam earthquake in 2003 had two heroes: people and bam airport. in bam earthquake, more than 10,000 injured people were taken to other cities by air evacuation.” (p19) 5.3. inefficient resources management the findings of this study showed that there is no defined process for mobilization and utilization of rescuers at local, regional, and national level. it is chaotic and based on individual decisions. one manager stated that: “in the response phase of bam earthquake the number of rescuers was about twice the region’s population and most of the resources were used by them.“(p14) and: “a field hospital with intensive care unit (icu) capabilities was set up with limited supplies and no mechanism in place for resupplying.” (p1) 5.4. lack of evaluation system so far, no system has been designed to assess the performance of various parts of iran’s healthcare system in disasters. to date, assessments have been limited to publication of some inaccurate descriptive data, such as the number of deaths and the number of patients transmitted to hospitals. 6. challenge related to medical care this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. sorani et al. 4 6.1. focus on traumatized patients in the healthcare system of iran, there is a misconception that all disaster patients are traumatic; therefore, there is no preparedness to respond to non-traumatic medical emergencies. “in the disaster response phase, a large number of patients with diabetes or cardiovascular emergencies need immediate care.” (p8) 6.2. focus on evacuation due to lack of disaster medical assistance teams (dmat), lack of advanced medical posts (amp) and presence of unskilled staff, ems focuses on patient evacuation to the outside area. 4. discussion in major emergencies and disasters, the capacity of emergency care systems is usually inadequate and it is likely that local community resources get overwhelmed (3, 16). emergency care may not be available, especially in the early hours after the disaster (17). in this situation, the public can play an important role in providing first aid. accordingly, some agencies across the world have now provided civilian-based prehospital guidelines, public education and exercises for communities (18). the results of our study showed that laypeople in iran play a confounding role in disaster management. other studies conducted in iran have demonstrated that people usually have inadequate knowledge about first aid interventions (19). nonetheless, they crowd around the scene and perform interventions that may worsen the problems of the injured person (20). overcrowding may act as a barrier for proper and timely prehospital interventions. in some cases laypeople’s involvement and overcrowding around the scenes have led to violence towards ems staff (21). another category of challenges identified by this study was infrastructure disruption. infrastructure disruption after disasters has also been pointed out by other researchers as a serious challenge (22, 23). infrastructure plays an important role in the hospital and prehospital emergency medical services in disasters. management of response teams, coordination between the medical staff, and other rescue teams, deployment of regional and national resources needs sustainable communication, which is usually disrupted in disasters. difficult access to the affected area was identified as another aspect of infrastructure disruption. after disasters, traffic jam and damage to roads slow down the relief effort. the last subcategory mentioned as a challenge by the study participants was vulnerability of local health facilities. similar to other developing countries, previous instances in iran have shown that local health facilities are damaged during disasters; therefore, patient evacuation to outside the affected area is needed (17, 24). godschalk suggests that community infrastructure must be resilient and designed to continue functioning under extreme hazardous conditions (25). the early phase of response is the best chance for influencing health related outcomes. therefore, early decisions are critical. the present study found that challenges related to information management system can be classified into two subcategories: issues related to patient tracking system and integrated hospital capacity information system. patient tracking systems are developed for several reasons, including registering and identifying patients, following up medical conditions, guiding patients’ distribution, setting priority for evacuation, locating patients and reuniting family members (26). disaster experience in iran shows that there are no integrated hospital information systems to collect, record, and share data about hospitals’ capacity and their surge capacity. according to the participants, lack of this system led to inappropriate distribution of casualties between hospitals. disaster response is a difficult career to get involved in without extensive experience in certain skill sets such as disaster medicine, triage, coordination, team work, mental health care, communication, and safety. according to the study participants, most iranian ems providers have inadequate skills in the field of disaster. for example, in the disaster plan of iran’s healthcare system, the need for activation of incident command system (ics) and emergency operation center (eoc) has been emphasized in the response phase, but many employees do not have enough knowledge, skills and motivation in this regard. similar findings were seen in some other studies (27). according to the participants, safety concerns must be addressed as a priority of iranian ems providers in disasters but they are not sufficiently trained or well-equipped with personal protective equipment. in iran’s past major disasters, most of the local healthcare facilities were disrupted and ems was forced to evacuate numerous casualties out of the affected area (28). according to the findings, there were two main problems in providing emc in disaster situation: first, lack of disaster protocols and second, resource management deficiency. participants believed that lack of dmats and amps, failure to execute triage, and lack of a plan for distribution of casualties led to chaotic evacuation of numerous casualties and overwhelming capacity of regional hospitals in large scale disasters. our results correspond to the study by juffermans j et al. (29). bam earthquake showed that aero-medical evacuation is the main and most effective way to transport disaster casualties (30). according to the study participants, iran’s health system does not have enough air-medical ambulances including medical helicopter or medical airplane. shortly after the disasters, lots of resources were allocated to the affected area by national and local organizations. the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e26 participants agreed that, there is no evaluation system for resource management, and therefore, inattention to incident leveling, at local, regional and national levels, leads to chaotic allocation of financial and human resources as well as equipment. they believed that many scarce resources are wasted in the response phase of disasters. it is necessary to assess and report the outcomes and processes of medical response measures in disasters. assessments can improve emergency medical response (31). based on the experiences of the participants, there is no indicator for assessment of ems performance and medical care outcomes. based on the participants’ points of view, while the ems plan focused on the trauma, a considerable number of patients are usually non-traumatized patients, including internal, gynecology and psychiatric emergencies. this finding is consistent with the finding of a study by klein (32). cases of chronic medical conditions or non-traumatic emergencies do not fit the traditional triage algorithm. all prehospital ems providers are trained in start algorithm, which is based on trauma situations. the participants in this study indicated that prehospital emergency plan focuses on evacuation. lack of dmats, lack of amps and inadequate skills of staff lead to rapid evacuation of all causalities even minor injuries with a “scoop and run” strategy instead of “stay and play”. this approach can lead to overcrowding in the eds and resources being overwhelmed (33). this qualitative study is one of the few studies gathering the viewpoints of various experts regarding prehospital ems in disaster in the iranian context. the findings point to a number of essential areas in need of improvement. 5. limitation as is the case in qualitative studies, the small number of participants is a limitation of this study, but all participants were experienced and expert and saturation was reached. constant comparison analysis was also used to validate data. since this is a qualitative study, it is not reasonable to seek generalizability, therefore, future research is needed in the same field. 6. conclusion the findings of this study showed that iran’s prehospital ems has been chaotic in past disasters. improvement of this process needs infrastructure reform, planning, training and public education. 7. appendix 7.1. acknowledgements the authors would like to thank all the participants for their contribution to the study. 7.2. author contribution all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 7.3. funding/support this paper was supported financially by school of health management and information sciences, iran university of medical sciences (iums/ shmis: 1394/34). 7.4. conflict of interest none declared. references 1. centre for research in the epidemiology of disasters. the human cost of natural disasters 2015: a global perspective. website. http://emdat.be/human_cost_natdis. published 26 june 2015, accessed 6 may, 2018. 2. van den berg b, grievink l, gutschmidt k, lang t, palmer s, ruijten m, et al. the public health dimension of disasters–health outcome assessment of disasters. prehosp disaster med. 2008;23(4):s55-9. 3. djalali a, hosseinijenab v, hasani a, shirmardi k, castren m, ohlen g, et al. a fundamental, national, medical disaster 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disasters in the netherlands. prehosp disaster med. 2010;25(2):127-36. 30. abolghasemi h, poorheidari g, mehrabi a, foroutan g. iranian military forces in the bam earthquake. mil med. 2005;170(10):859-61. 31. nilsson h, vikstrom t, jonson co. performance indicators for initial regional medical response to major incidents: a possible quality control tool. scand j trauma resusc emerg med. 2012;20:81. 32. klein kr, nagel ne. mass medical evacuation: hurricane katrina and nursing experiences at the new orleans airport. disaster manag response. 2007;5(2):56-61. 33. adini b, aharonson-daniel l, israeli a. load index model: an advanced tool to support decision making during mass-casualty incidents. j trauma acute care surg. 2015;78(3):622-7. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2019; 7 (1): e6 rev i ew art i c l e a comparison between the ability of revised trauma score and kampala trauma score in predicting mortality; a meta-analysis shahram manoochehry1, masoud vafabin2, saeid bitaraf3, ali amiri1∗ 1. trauma research center, baqiyatallah university of medical sciences, tehran, iran. 2. shiraz university of medical sciences, shiraz, iran. 3. department of epidemiology and biostatistics, iran university of medical sciences, tehran, iran. received: september 2018; accepted: september 2018; published online: 15 january 2019 abstract: introduction: describing injury severity in trauma patients is vital. in some recent articles the revised trauma score (rts) and kampala trauma score (kts) have been suggested as easily performed and feasible triage tools which can be used in resource-limited settings. the present meta-analysis was performed to evaluate and compare the accuracy of the rts and kts in predicting mortality in low-and middle income countries (lmics). methods: two investigators searched the web of science, embase, and medline databases and the articles which their exact number of true-positive, true-negative, false-positive, and false-negative results could be extracted were selected. sensitivity and subgroup analysis were performed using stata software version 14 to determine the factor(s) affecting the accuracy of the rts and kts in predicting mortality and source(s) of heterogeneity. results: the heterogeneity was high (i2 > 80%) among 11 relevant studies (total n = 20,631). while the sensitivity of the kts (0.88) was slightly higher than rts (0.82), the specificity, diagnostic odds ratio, negative likelihood ratio, and positive likelihood ratio of the kts (0.73, 20, 0.16, 3.30, respectively) were lower than those of the rts (0.91, 45, 0.20, 8.90, respectively). the area under the summary-receiver operator characteristic curve for kts and rts was 0.88 and 0.93, respectively. conclusion: however, regarding accuracy and performance, rts was better than kts for distinguishing between mortality and survival; both of them are beneficial trauma scoring tools which can be used in lmics. further studies are required to specify the appropriate choice of the rts or kts regarding the type of injury and different conditions of the patient. keywords: revised trauma score; kampala trauma score; mortality cite this article as: manoochehry sh, vafabin m, bitaraf s, amiri a. a comparison between the ability of revised trauma score and kampala trauma score in predicting mortality; a meta-analysis. arch acad emerg med. 2019; 7(1): e6. 1. introduction t raumatic injury as one of the major causes of morbidity and mortality remains a worldwide concern. according to the world health organization (who) 16% of the global burden of disease refers to injuries (1). on the other hand, traumatic injuries are the cause of about 5.8 million deaths in the world. according to statistics 90% of these deaths happen in low-and middle income countries (lmics) (2, 3). furthermore, injuries disable about 78 mil∗corresponding author: ali amiri; trauma research center, baqiyatallah hospital, molla sadra avenue tehran, iran. postal code: 1983969411 mail: aliamiri.aa@hotmail.com mobile: +989124374291 fax: +982122439784 lion people and account for up to 30% of hospital admissions. the burden of injuries supposed to be much higher in lmics. in this regard, about 88.3% of lost disability-adjusted life years (dalys) and 87.9% of road traffic deaths is reported from these areas (4, 5). regarding the great trauma burden in countries with such a resource-limited setting, developing protocols for allocating resources in a strategically good way to minimizes injury-related morbidity and mortality, and maximizes patient survival seems necessary. multiple injury scoring systems have been used in high-income countries (hics) since 1970s for triage, injury description and outcome, and mortality prediction, such as injury severity score (iss), revised trauma score (rts), and the trauma and injury severity score (triss) (6, 7). rts is known as the current standard physiologic scoring tool used in trauma setthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. manoochehry et al. 2 ting and research in both hics and lmics, which is based on physiologic variables of systolic blood pressure (sbp), respiratory rate (rr) and a higher weight variable glasgow coma scale (gcs), comparing to other variables (8-11). a review by o’reilly et al. indicated that the rts and iss used in trauma registries in lmics are superior to other injury scoring systems (12). however, these scoring systems perform well in developed countries and their calculation and performance require notavailable diagnostic tools in resource-limited setting and can be difficult to achieve. in 1996, the kmapala trauma score (kts) a simplified scoring system, was developed to specifically address this problem in resource-limited settings. it reflects sbp, rr, patient age, number of serious injuries and neurologic status (13, 14). some recent articles have been mentioned the kts and rts as easily performed and feasible triage tools suggested to be used instead of other complicated and difficult ones such as triss (15, 16). the mortality predictive ability of kts and rts have been compared in various studies in many countries with different methodologies. different results on the comparison of the kts and rts power in prediction of mortality has been reported in these studies (3, 15, 17-21). in spite of the apparent lack of consistent results due to the heterogeneity among studies, a metaanalysis has not been yet performed. according to the fact that kts was developed to specifically address the difficulty of calculation and performance of other trauma scoring systems in lmics, we performed a systematic review and metaanalysis to show which one of kts or rts has better accuracy and precision in predicting mortality in lmics. 2. methods: 2.1. search strategy and study selection here, regardless of publication status, studies of the mortality predictive ability of the rts and kts were included. two investigators (aa and shm) carried out a systematic search using the electronic databases such as embase, web of science, and medline from their commencements until july 2018. the search strategy in medline used the following terms: ((“revised trauma score”[tiab] or rts[tiab] or “kampala trauma score”[tiab] or kts[tiab]) and (((sensitivity[tiab] or specificity[tiab]) or “receiver operating characteristic curve”[tiab]) or roc[tiab] or prognosis[tiab] or “prognostic value” [tiab] or prediction[tiab] or “predictive value” [tiab])). the search strategy in web of science and embase used the following terms: revised trauma score, or rts, or kampala trauma score, or kts; and sensitivity, or specificity, or receiver operating characteristic curve, or roc, or prognosis, or prognostic value, or prediction, or predictive value. furthermore, searching all potentially eligible references cited in related review and original articles were carried out manually in google scholar and google search engines. if the full text was not accessible or the required details were not completely available in the full text, we tried to get the details from the authors by email. 2.2. inclusion and exclusion criteria in order to include certain studies in the present study, they should have evaluated the performance of the rts or kts for patient mortality prediction in lmics, and also the exact number of true-positive, true-negative, false-positive, and false-negative results could be extracted either directly or indirectly. the studies with the following criteria were excluded: did not evaluate the performance of rts or kts in predicting patient mortality; were not conducted in lmics; were not english-language; and letters to editors or conference abstracts. the two reviewers who carried out the literature search also individually made decisions and selected studies regarding inclusion criteria (aa and shm). 2.3. data extraction and quality assessment using two reviewers (aa and shm) the following details were extracted from included studies independently: study location, year of publication, the first author’s surname, study design, age, number of cases, proportion of male subjects, area under the receiver operator characteristic (roc) curve (auc), cut-off value, sensitivity, and specificity. two reviewers (aa and shm) individually used the quality assessment of diagnostic accuracy studies-2 (quadas-2) tool which is widely used to assess the quality of systematic reviews of diagnostic studies (22). the quadas-2 is four-key domain tool: patient selection, index test, reference standard, and flow and timing. “concerns regarding applicability” and “risk of bias” were assessed for the first three domains and all four domains, respectively (each item answered as “unclear”, “yes”, or “no”). to evaluate the “risk of bias”, a low risk of bias is defined as “yes” answer to all signaling questions in a domain. if any signaling question has been answered as “no”, it indicated a high risk of bias. “applicability” section was judged as same as the bias section, excluding signaling questions. 2.4. statistical analysis the i2 test was used to evaluate the heterogeneity which was defined as low, moderate, and high in thresholds of 25%, 50%, and 75%, respectively. we used true-positive, false-positive, true-negative, and false-negative parameters to calculate the sensitivity, specificity, diagnostic odds ratio (dor), auc, positive likelihood ratio (plr), and negative likelihood ratio (nlr). based on differences in inclusion criteria and study population or type of injury, we selected and excluded specific studies, and then performed sensitivity analysis to identify if the results have been affected by these this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2019; 7 (1): e6 table 1: general characteristics of the included studies first author country sample size morta-lity year age ( years) male (%) tool cutoff value tp fp fn tn auc sen (%) spe (%) ahun turkey 100 0.120 2014 ≥18 77 rts 5.97 5 4 7 84 0.68 41.67 95.45 eftekhar iran 7211 0.038 2005 mean, 32.5 76 rts 4.09* 27 3 2463 1 4474 0.91 99.80 64.50 macleod uganda 150 0.255 2003 ≥15 89.3 rts kts 7.40 13.0 34 35 37 59 4 3 75 53 0.87 0.84 89.5 92.1 67.0 47.3 nakhjavan-shahraki iran 2184 0.057 2017 ≥18 75.56 rts 1.0 88 53 35 1972 0.86 71.54 97.38 nakhjavan-shahraki iran 814 0.031 2017 ≤18 74.32 rts 1.0 22 14 4 774 0.94 84.6 98.2 oluwadiya nigeria 186 0.065 2010 mean, 36.7 73.1 rts kts 5.7 12.0 10 12 29 51 2 0 145 123 0.88 0.91 83.3 100 83.3 70.7 owor uganda 1305 0.036 2001 . . kts 12.0 42 151 5 1107 0.87 90.0 88.0 roy india 4091 0.22 2016 mean, 36.5 83 rts kts 7.0 12.0 574 595 486 716 326 305 2705 2475 0.81 0.74 63.8 66.07 84.78 77.55 senturk turkey 153 0.118 2013 ≥18 81 rts 4.08 13 15 5 120 0.80 72.0 89.0 valderrama-molina colom bia 4085 0.093 2016 ≥15 84.2 rts 6.37 33 0 1010 50 2695 0.86 86.77 72.75 yousefzadeh-chabok iran 352 0.139 2016 mean, 71.5 53.4 rts 6.0 30 3 19 300 0.87 62.0 99.0 rts, revised trauma score; kts, kampala trauma score; tp, true-positive; fp, false-positive; fn, false-negative; tn, true-negative; sen, sensitivity; spe, specificity; auc, area under the receiver operator characteristic curve. * because the cut-off value could not be extracted from the study, we set the standard cut-off value as said by champion et al (6, 7). table 2: quality assessment of included studies using quadas-2 study risk of bias applicability concerns patient selection index test reference standard flow and timing patient selection index test reference standard ahun 1? § © © © © © eftekhar © © © © © © © macleod © § © § © © © nakhjavanshahraki © © © © © © © nakhjavanshahraki ? © © © © © © oluwadiya © 2? © 3? © © © owor § ? © © § © © roy © § © § © © © senturk © © © © © © © valderramamolina © ? © © © © © yousefzadehchabok ? © © © © © © ©: low risk; §: high risk; ?: unclear risk 1: the sampling technique (consecutive or random) is undisclosed, 2: the interpretation of index test results without knowledge of the results of the reference standard was unknown or pre-specification of threshold was unclear, 3: the proportion of study population, in which included in analysis is unknown. quadas-2 quality assessment of diagnostic accuracy studies 2. table 3: pooled estimates of the revised trauma score and kampala trauma score tool sensitivity specificity plr nlr dor rts 0.82 (0.66-0.92) 0.91 (0.81-0.96) 8.9 (4.5-17.8) 0.20 (0.10-0.39) 45 (21-99) kts 0.88 (0.70-0.96) 0.73 (0.57-0.85) 3.3 (2-5.6) 0.16 (0.06-0.44) 20 (6-69) all measures were presented with 95% confidence interval. rts, revised trauma score; kts, kampala trauma score; ci, confidence interval; plr, positive likelihood ratio; nlr, negative likelihood ratio; dor, diagnostic odds ratio. exclusions or not. we performed subgroup analyses based on the number of patients. regarding the distribution of sample size among studies, we categorized them into two different groups as small and big samples. thus, studies with a sample this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. manoochehry et al. 4 table 4: sensitivity analysis results first author sensitivity (95%ci) specificity (95%ci) auc i2(%) none* 0.82 (0.66-0.92) 0.91 (0.81-0.96) 0.93 100 macleod 0.81 (0.62-0.92) 0.92 (0.83-0.97) 0.94 100 nakhjavan-shahraki 0.82 (0.63-0.92) 0.89 (0.78-0.95) 0.92 100 senturk 0.83 (0.65-0.93) 0.91 (0.80-0.96) 0.94 100 valderrama-molina 0.82 (0.63-0.92) 0.92 (0.82-0.97) 0.94 100 yousefzadeh-chabok 0.84 (0.67-0.93) 0.89 (0.78-0.94) 0.93 100 *no article was excluded. ci, confidence interval; auc, area under the receiver operator characteristic curve. table 5: subgroup meta-analysis for the revised trauma score subgroup sensitivity (95%ci) specificity (95%ci) auc i2(%) all 0.82 (0.66-0.92) 0.91 (0.81-0.96) 0.93 100 sample size < 1000 0.76 (0.62-0.86) 0.94 (0.83-0.98) 0.89 97 sample size ≥ 1000 0.89 (0.57-0.98) 0.85 (0.64-0.95) 0.93 100 ci, confidence interval; auc, area under the receiver operator characteristic curve. size <1000 patients defined as small sample. the publication bias was assessed using a funnel plot. stata version 14 was used for all statistical analysis and a statistically significant difference was defined as a p-value <0.05. 3. results: the search strategy initially returned 1341 studies after removing the duplicates (figure 1). titles and abstracts reading led to the finding of 102 studies that used the rts or the kts as a prognostic method for mortality prediction. among these 102 records, 14 articles were excluded due to not evaluating of the performance of the rts or kts in predicting mortality. 62 added records were excluded since the exact number of true-positive, false-positive, true-negative and falsenegative test results could not be obtained, and also a total number of 5 studies that were not published in english, were excluded. an additional 10 records were excluded because they did not carry out in lmics. finally, after application of the mentioned-inclusion criteria, 11 eligible studies evaluating the performance of the rts or kts in mortality prediction in lmics were included in this meta-analysis (table 1) (11, 15, 16, 21, 23-29). the quality assessment of the included 11 studies are shown in table 2 and figure 2. the studies were conducted in six different countries, including colombia, india, iran, nigeria, turkey and uganda. a total of 20,631 patients (ranged from 100 to 7211) were evaluated. the majority of the sample consisted of men (76.68%). seven of 11 studies assessed only the rts (11, 23-25, 27-29), one study assessed only the kts (26), and three of the studies assessed both the rts and kts (15, 16, 21). while one study was based in a level i trauma center, other studies included patients from hospitals (28). the mortality rate and cut-off point (a threshold for mortality prediction) were different among these studies. if the exact number of all truepositive, false-positive, true-negative and false-negative test results were not directly obtained from the studies, they have been calculated indirectly from the number of patients, mortality values, sensitivity and specificity. using a random-effects model, we pooled related statistical parameters owing to the high level of heterogeneity (i > 80%). for the rts, the pooled estimates were 0.82 (95% ci: 0.66– 0.92) for sensitivity, 0.91 (95% ci: 0.81–0.96) for specificity, 8.90 (95% ci: 4.50–17.80) for plr, 0.20 (95% ci: 0.10–0.39) for nlr, 45 (95% ci: 21–99) for dor. for the kts, the pooled estimates were 0.88 (95% ci: 0.70–0.96) for sensitivity, 0.73 (95% ci: 0.57–0.85) for specificity, 3.30 (95% ci: 2.00–5.60) for plr, 0.16 (95% ci: 0.06–0.44) for nlr, 20 (95% ci: 6–69) for dor (table 3). figure 3 shows the summary receiver operator characteristic curves (sroc) for the rts and kts plots. the auc for the rts was higher comparing to that for the kts (0.93 vs 0.88, respectively). in order to determine the source of heterogeneity, sensitivity analysis was conducted (table 4). the studies by yousefzadeh-chabok et al. and nakhjavan-shahraki et al. were removed because only elders and children samples were included, respectively (23, 29). the studies by senturk et al. and macleod et al. were removed because they included only multiple blunt and major trauma patients, respectively (15, 25). the study by valderrama-molina et al. was removed because it was the only study conducted in a fourth level hospital which is equivalent to a level one trauma center in the usa (28). the i2 value for sensitivity did not change, and the sensitivity value was similar to that found without excluding mentioned studies. subgroup meta-analysis was performed by classifying studies according to their number of samples. the changes in sensitivity and specificity values are shown in table 5. due to the low number of studies, we could not this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2019; 7 (1): e6 figure 1: flow diagram of systematic search for the meta-analysis considering the ability of the revised trauma score and kampala trauma score in predicting mortality. rts, revised trauma score; kts, kampala trauma score; lmics, low and middle-income countries. perform this analysis in detail for kts. therefore, only subgroup meta-analysis for rts was performed. in order to explore publication bias (which obtained p-value of 0.2 did not suggest it), a funnel plot asymmetry analysis was used (figure 4). 4. discussion: although the kts was developed to simplify the mortality prediction in lmics, the present meta-analysis showed high accuracy of the kts and rts in predicting mortality with a slightly better performance for rts. the specificity, dor, nlr, and plr of the kts were slightly lower than those of the rts, while the sensitivity of the kts was slightly higher than rts. in emergency settings, physicians are always challenging with the issue of classifying the trauma patients according to the severity of their trauma (24). in this regard, different trauma scoring systems are frequently used for diagnosing high risk patients. however, each one of them has its own advantages and disadvantages. trauma related deaths are classified into three different groups. group one (50%) consists of patients who die at the scene (often because of severe vascular injury or major head trauma). group two (30%) includes patients with hospital admission who die within the first hours of admission called “golden hour”. the deaths of this group are usually because of major head, thorax or abdominal trauma. group three (20%) includes those who die at a later time (usually due to multi-organ failure or sepsis). the mortality rate of two later groups can be decreased through fast and efficient treatment approaches (26, 27, 30, 31). therefore, a precise selection of trauma scoring system especially in lmics with a much higher rate of trauma is an this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. manoochehry et al. 6 figure 2: quality assessment of included studies using quadas-2. figure 3: summary receiver operating characteristic curves (sroc) of revised trauma score (left) and kampala trauma score (right). auc, area under the receiver operating characteristic curve. essential issue. however, the rts necessitates the use of a formula to admit the gcs, respiratory rate and systolic blood pressure and it remains the most commonly used pre-hospital trauma scoring system. moreover, the rts is considered as one of the most easily calculated triage tools available shortly after trauma admission (25, 32, 33). like the rts, the kts is an easily performed trauma scoring system without specific requirements such as finance resource, the associated manpower need and retrospective review of injuries. therefore, it is a reasonable and feasible choice for front-line triage usage (15). some recent articles have been mentioned the kts and rts as easily performed and feasible triage tools suggested to be used instead of other complicated tools such as triss (15, 16). different results on the comparison of the mortality predictive ability of kts and rts has been reported. despite the apparent lack of consistent results due to the heterogeneity among studies, a meta-analysis has not been yet performed to compare the accuracy of rts and kts. according to the fact that kts was developed to specifically address the difficulty of calculation and performance of other trauma scoring systems in lmics, we performed a systematic review and meta-analysis to show which one of kts or rts has better accuracy and precision in predicting mortality in lmics. stability of sensitivity and specificity can be integrated to make a comprehensive test performance named likelihood ratios, which is superior to their components. the plr of the rts (8.90) was higher than that of the kts (3.30), with a positive rts or kts outcome indicating an approximately nine and three-fold higher risk of mortality, respectively. however, it should be considered that plr should be more than 10 so as to be useful. the slightly higher nlr for the rts this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2019; 7 (1): e6 figure 4: the funnel plot for assessment of publication bias. (0.20) suggests that it had a slightly lower accuracy comparing to the kts (0.16) for predicting survival. the dor combines the sensitivity and specificity values into a single number indicating the test accuracy (between zero and infinity). higher dor values indicate higher accuracy of a test (better discriminatory performance), and a dor value of 1.0 indicates that the rts or kts does not distinguish between mortality and survival. in the present study, the higher dor of the rts (dor = 45) indicates that it is more capable than the kts (dor = 20) in distinguishing between mortality and survival. in addition to summarizing the sensitivity and specificity, the sroc curve is a more effective index than the other indices (since the threshold effect has no influence on it). based on the sroc curve in our study, the auc of the rts (0.93) was slightly higher than that of the kts (0.88). all of these indices indicate that the overall accuracy of the rts and kts in predicting mortality was as high as expected, and both of them had high sensitivity and specificity. in the three studies evaluating the rts and kts, two studies (16, 21) concluded that the accuracy of the rts and kts for predicting mortality was similar, while another study showed that the rts is superior to the kts (15). based on the obtained results, we found that the rts has slightly higher accuracy than the kts in predicting mortality. the accuracy of rts in predicting mortality has been affected by some factors and was different in each subgroup. the sensitivity value of rts was higher with sample size ≥1000, indicating better result of mortality prediction in studies with a higher sample size. moreover, the sensitivity was not changed by removing the study of valderrama-molina et al. (which was the only study conducted in a level one trauma center) indicating no difference of the rts performance in a hospital or a level one trauma center. the sensitivity value of rts increased after removing the study by yousefzadechabok et al., which shows worse performance of rts in elder populations. after removing the specific studies, the heterogeneity did not change. the subgroup meta-analysis showed that the differences in the number of patients between studies contributed to the heterogeneity. thus, studies with a larger sample size contributed more to the heterogeneity. the differences in the populations and countries can also effect on the heterogeneity. the present study had several limitations. first, we used only english written studies. second, due to the lack of data, we focused only on the ability of mortality prediction and excluded physiology and age that could influence the trauma outcome. third, because of the limited data, we could not analyze additional factors such as type of injury, age, ethnic group and treatment which might change the rts or kts accuracy. to the best of our knowledge, this is the first study on the ability of the rts and kts in mortality prediction as a meta-analysis. 5. conclusion briefly, high accuracy of both the rts and kts for predicting mortality in lmics has been confirmed. however, regarding accuracy and performance, the rts was better than the kts for distinguishing between mortality and survival; both of them are beneficial trauma scoring tools which can be used in resource-limited settings. further studies are required to specify the appropriate choice of the rts or kts regarding the type of injury and different conditions of the patient. 6. appendix 6.1. acknowledgements not applicable. 6.2. authors contributions a.a.; designed the study, carried out the systematic search, selected the studies, performed the quality assessment, and co-wrote the paper. s.b.; performed statistical analyses. m.v.; co-wrote the paper. sh.m.; performed systematic search, study selection, and quality assessment. authors’ orcids shahram manoochehry: 0000-0002-0424-1763 masoud vafabin: 0000-0003-0386-7200 saeid bitaraf: 0000-0003-4688-9856 ali amiri: 0000-0002-8602-9052 6.3. funding support none. 6.4. conflict of interest none. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem sh. manoochehry et al. 8 references 1. organization wh. the world health report 2002: reducing risks, promoting healthy life: world health organization; 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9(1): e4 https://doi.org/10.22037/aaem.v9i1.994 or i g i n a l re s e a rc h straddle versus conventional chest compressions in a confined space; a comparative study praphaphorn supatanakij1, chaiyaporn yuksen1∗, terapat chantawong1, pilaiwan sawangwong1, chetsadakon jenpanitpong1, jirayoot patchkrua1, ponlawat kanchayawong1 1. department of emergency medicine, faculty of medicine ramathibodi hospital, mahidol university, bangkok, thailand. received: september 2020; accepted: october 2020; published online: 14 november 2020 abstract: introduction: when cardiac arrest occurs in a confined space, such as in an aircraft or ambulance, kneeling by the patient’s side may be difficult. straddle chest compression is an alternative technique that can be used in a confined space. this study was performed to compare the quality of chest compressions in straddle versus conventional cpr on a manikin model. methods: the participants were randomized into two groups using the sequential numbered, opaque, sealed envelope method chosen through block-of-four randomization: straddle and conventional chest compression technique. each participant performed a maximum of 4 minutes of hands-only chest compressions, and quality parameters (compression rate and depth) were recorded from the defibrillator’s monitor. results: 124 participants with mean age of 26.67 ± 6.90 years (27.58% male) were studied. there was no difference in the mean compression rate between the conventional and straddle chest compression techniques (126.18 ± 17.11 and 127.01 ± 21.01 compressions/min, respectively; p = 0.811) or their mean compression depth (43.8 ± 9.60 and 43.4 ± 9.10 mm, respectively; p = 0.830). the participants’ comfort and fatigue were assessed through changes in their vital signs. in both methods, statistically significant differences were observed in vital signs before and after performing chest compression, but the differences were not clinically significant. in addition, there was no difference between the 2 groups in this regard. conclusion: the quality of cpr using the straddle chest compression was as good as conventional chest compression technique. no significant differences were found in the quality of chest compressions or the participants’ comfort and fatigue levels. keywords: cardiopulmonary resuscitation; heart arrest; heart massage; emergency medical service; ambulances cite this article as: supatanakij p, yuksen c, chantawong t, sawangwong p, jenpanitpong c, patchkrua j, kanchayawong p. straddle versus conventional chest compressions in a confined space; a comparative study. arch acad emerg med. 2021; 9(1): e4. 1. introduction sudden cardiac arrest can occur in either an emergency room or outside a hospital, which is one of the leading causes of death in many countries worldwide (1). the survival rate after receiving life support inside and outside hospitals ranges from 2% to 10% and from 7.4% to 27%, respectively (2-5). basic life support (bls) after sudden cardiac arrest can increase the survival rate (6). chest compression is an important step in basic life support, which is considered a standard procedure for healthcare providers and lay-rescuers at the scene of sudden car∗corresponding author: chaiyaporn yuksen; department of emergency medicine, faculty of medicine ramathibodi hospital, mahidol university bangkok, thailand. email: chaipool0634@hotmail.com, tel: 66894726911, orcid:0000-0002-4890-7176 diac arrest. chest compression is more effective when the patient is lying in supine position on a relatively hard surface such as ground or floor (7, 8). the compression depth should be at least 2 inches or 5 centimeters, but not exceed 2.5 inches or 6 centimeters for adult cardiac arrest patients (9, 10). the chest should be released and allowed to recoil completely before the initiation of another compression (11, 12). the compression rate should be at least 100-120 compressions per minute. it is important to ensure that no interruptions occur while performing chest compression (13, 14). those performing cardiac massage for patients with sudden cardiac arrest should not stop chest compression unless the patient should be evacuated from the scene or electrical defibrillation should be performed, otherwise its effectiveness will decrease. (15). in out-of-hospital cardiac arrest (ohca), some patients should be immediately transported to a hospital to receive definite treatments such as extracorthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. supatanakij et al. 2 poreal cardiopulmonary resuscitation in refractory shockable cardiac arrest, thus, chest compressions must be continued during transport. however, performing chest compression when positioned beside the patient on a moving vehicle will alter the quality of chest compression and cause injury to providers. another situation is in an aircraft where it may be difficult for providers to kneel down and perform chest compression when positioned lateral to the patient due to confined space. alternative techniques are available to perform chest compression in confined space areas such as ambulances or aircrafts (16). chest compression when the provider is positioned over the patient’s head (over-the-head cpr) or straddled over the patient’s legs (straddle cpr) may be useful in situations where space is limited (17, 18). as mentioned above, straddle cpr may be useful to perform chest compression during transportation of the patient on an ambulance with high speed and limited spaced, because straddling over the patient’s legs is stronger and safer than standing beside the stretcher. however, the quality of chest compression in straddle technique has not been studied in detail. the objectives of this study were to 1) compare the quality of conventional and straddle chest compressions using a manikin model and 2) study the comfort and fatigue of providers by measuring the changes in their vital signs before and after performing the two different chest compression techniques. 2. methods 2.1. study design and setting this was a cross-sectional comparative study with stratified randomization of participants. the study was conducted from december 2016 to january 2017 at the faculty of medicine ramathibodi hospital, a university-affiliated super tertiary care hospital in bangkok, thailand. participants consisted of individuals in both healthcare (emergency physicians, general practitioners, nurses, ambulance staffs, medical and paramedic students) and non-healthcare (airline staff, flight attendants, and cabin crew members) professions, were enrolled to the study then provided written informed consent. the participants were stratified into two groups according to their profession, and were then divided into straddle chest compression or conventional chest compression group using the sequential numbered, opaque, sealed envelope random sampling method through blockof-four randomization. all participants studied a diagram showing the technique of chest compression. the ethics committee of faculty of medicine, ramathibodi hospital, mahidol university, bangkok, thailand approved of this study in terms of human rights related to research involving human subjects (ethics code: mura2017/23). 2.2. participants the participants in this study were emergency physicians, general practitioners, nurses, ambulance staff, and medical and paramedic students of faculty of medicine ramathibodi hospital. airline staff, flight attendants, and cabin crew members of the airports of thailand public company limited (aot) were also included. the exclusion criteria were participants who discontinued chest compression due to injury and occurrence of any problems for the study devices during the study. 2.3. data gathering all participants’ characteristics including: age, sex, body mass index, occupation, previous bls training, previous experience in chest compression, and number of exercises per month were recorded. vital signs of participants including their systolic blood pressure, pulse rate, and respiratory rate were measured immediately both before and after the procedure. participants in each group pressed down on the chest of laerdal® resusci anne manikin model connected with the zoll® x series® monitor defibrillator and cpr stat-padz® multi-function electrode pads that provided continuous and summarized recording of chest compression quality. participants were blinded to the real-time quality results while performing chest compression to reduce potential bias. they were required to perform continuous compressions on the chest without stopping until they felt too tired to continue, this period did not exceed 4 minutes. the following variables were recorded for both conventional and straddle chest compression techniques: overall mean compression rate and overall mean compression depth. mean compression rate and mean compression depth were also recorded at each specific time interval (minutes 0-1, 1-2, 2-3 and 3-4, respectively). 2.4. statistical analysis in accordance with the study by lei z and qing h (19), which compared the quality of conventional chest compression on the floor and straddle chest compression on the moving ambulance stretcher using a manikin model, the sample size was calculated using stata version 12.0 (statacorp, college station, tx, usa). we performed two-sample comparisons of the mean with a power of 0.9, sample size ratio of 1:1, p-value of 0.05, and two-sided tests. the minimum required sample was 124 participants. the data were recorded using microsoft excel 2010 (microsoft corporation, redmond, wa, usa) and were analyzed using stata version 14.0. chi-square or exact probability test were applied to compare independent categorical variables, while independent t-test were used to compare continuous variables. paired t-test or wilcoxon signedrank test were used to compare dependent continuous varithis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e4 ables according to data distribution. p-value of <0.05 was considered statistically significant. 3. results 3.1. baseline characteristics of participants there were 124 enrolled participants in this study, which consisted of 111 (89.5%) individuals in the healthcare professions and 13 (10.5%) in non-healthcare professions. nobody discontinued the chest compression to be excluded. participants were divided into 2 groups; 60 in the conventional chest compression and 64 in the straddle chest compression group. differences in baseline characteristics were not statistically significant between the two groups (table 1). 3.2. comparisons as shown in table 2, there were no statistically significant difference in the quality of chest compression in terms of the overall mean compression rate (p = 0.863) and depth (p = 0.830). the fatigue associated with conventional and straddle chest compression were assessed by measuring the participants’ vital signs before and after performing the compression. although the systolic blood pressure, pulse rate, and respiratory rate were significantly different before and after performing the compression in both groups, the differences were not clinically significant (table 3). 4. discussion chest compression is a lifesaving procedure, which increases survival rate among cardiac arrest patients, especially in outof-hospital cardiac arrest (ohca), where survival rate is low. according to recommendations of the american heart association (aha) in 2015, patients with cardiac arrest must be immediately resuscitated by performing high-quality chest compression with a compression rate of about 100-120 compressions per minute, compression depth should be between 2-2.5 inches or 5-6 centimeters. the chest should be released and allowed to completely recoil before initiating another compression and unnecessary interruptions should not occur in performance of chest compression. conventional chest compression by kneeling or positioning lateral to the patient’s side may be difficult and inappropriate in places such as an aircraft or high-speed moving ambulance, where the spaces are confined or limited. straddle chest compression is an alternative method, which allows for rescuers to continue chest compression without unnecessary interruption. in the present study, which aimed to compare the quality of straddle and conventional chest compression technique on a manikin model, the results revealed that there are no statistically significant differences in compression rate or depth between the two techniques neither overall nor at each specific time point (minutes 0-1, 1-2, 2-3 and 3-4, respectively). the overall mean compression rate (throughout the 4-minute evaluation period) was not significantly different between the two groups (125 compressions/min in conventional and 126 compressions/min in straddle technique), which were faster than the standard recommendation by the aha2015 (100–120 compressions/min). the overall mean compression depth was also not significantly different between the two groups (43.80 ± 9.60 mm in conventional and 43.90 ± 9.10 mm in straddle technique). the compression depth of both techniques was lower than the standard recommendation by the aha2015 (50–60 mm). these key results suggest for further training to maintain high quality chest compression in rescuers, both those in healthcare professions and those in non-healthcare professions. the participants’ comfort and fatigue were assessed by measuring changes in their vital signs, there were no statistically significant differences in these regards between the two techniques. however, vital signs slightly increased after performing chest compressions in both groups but they were not clinically significant. in a previous study by handley aj and handley ja (17), which aimed to compare the quality of performing chest compressions in a narrow area by two techniques: straddle over the head and straddle over the body, the result revealed that the two alternative techniques were useful in situations where space was limited. lei z and qing h (19) also compared the quality of standard chest compression performed on the floor and straddle chest compression performed on a stretcher using a manikin model. the result showed no difference in chest compression quality between these two compression techniques. straddle chest compression can be performed both in-hospital and out-of-hospital depending on the situation. for patients with in-hospital cardiac arrest, straddle chest compression can be performed on the stretcher while transporting patients to operating theater or catheterization laboratory. straddle chest compression can also be performed for out-of-hospital cardiac arrest patients who are in a confined space or who are in moving ambulances due to the need for immediate transport to receive definite treatment. 5. limitation our study has some limitations. first of all, a manikin model is unrealistic so the result of study must be cautiously interpreted and may not be generalizable to real clinical situations. second, most of the participants were in the healthcare profession with variations in terms of experience and skills so the study’s results may not be generalizable to real-life rescuers that consists of both healthcare and non-healthcare workers who will encounter out-of-hospital cardiac arrest patients. third, the experiment was conducted by placing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. supatanakij et al. 4 table 1: comparing the baseline characteristics of participants between conventional and straddle chest compression group characteristics conventional (n = 60) straddle (n = 64) p-value age (years) mean ± sd 25.77 ± 6.60 27.58 ± 7.21 0.149 gender male 40 (66.67) 40 (62.50) 0.708 female 20 (33.33) 24 (37.50) bmi (kg/m2) mean ± sd 23.69 ± 5.11 22.76 ± 4.55 0.286 occupation healthcare 54 (90.00) 57 (89.06) 0.893 non-healthcare 6 (10.00) 7 (10.94) previous bls training yes 44 (73.33) 52 (81.25) 0.390 no 16 (26.67) 12 (18.75) previous experience in chest compression yes 39 (65.00) 45 (70.31) 0.568 no 21 (35.00) 19 (29.69) exercise for physical fitness (/month) 0 18 (30.00) 14 (21.88) 1-4 times 36 (60.00) 46 (71.88) 0.408 ≥ 5 times 6 (10.00) 4 (6.25) data are presented as mean ± standard deviation or number (%). bmi: body mass index; bls: basic life support. table 2: comparison of quality of chest compression between conventional and straddle chest compression techniques variable conventional (n = 60) straddle (n = 64) p-value compression (compressions per minute) overall 126.18 ± 17.11 127.01 ± 21.01 0.811 minute 0-1 126.89 ± 17.18 127.47 ± 19.95 0.863 minute 1-2 125.97 ± 17.47 125.84 ± 20.56 0.971 minute 2-3 124.23 ± 16.59 126.02 ± 20.32 0.634 minute 3-4 124.43 ± 17.72 121.81 ± 17.62 0.539 compression depth (millimeters) overall 43.80 ± 9.60 43.40 ± 9.10 0.830 minute 0-1 45.60 ± 8.10 45.70 ± 8.60 0.945 minute 1-2 43.18 ± 9.83 43.00 ± 9.70 0.937 minute 2-3 41.89 ± 11.14 39.76 ± 10.07 0.325 minute 3-4 39.90 ± 11.27 39.20 ± 10.07 0.767 data are presented as mean ± standard deviation. table 3: comparison of vital signs before and after chest compression between conventional and straddle chest compression techniques vital signs conventional (n = 60) straddle (n = 64) before after p before after p sbp (mmhg) 125.5 ± 18.2 132.8 ± 7.5 <0.001 120.8 ± 5.1 131.8 ± 3.7 <0.001 pr (/min) 83.5 ± 18.2 93.6 ± 15.4 <0.001 79.9 ± 13.9 93.15 ± 16.7 <0.001 rr (/min) 16.6 ± 1.0 23.9 ± 3.4 <0.001 16.3 ± 0.7 23.7 ± 3.7 <0.001 data are presented as mean ± standard deviation. sbp: systolic blood pressure; pr: pulse rate; rr: respiratory rate. the manikin on the floor, not on a stretcher in a moving ambulance. thus, the result may not be the same in a situation that chest compression must be continued while transporting the patients. 6. conclusion the present study showed that the quality of chest compression using straddle technique was as good as conventional technique. no significant differences were found in the quality of chest compression or the participants’ comfort and fathis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e4 tigue levels. 7. declarations 7.1. acknowledgements we thank angela morben, dvm, els, from edanz group (https://en-author-services. edanzgroup.com), for editing a draft of this manuscript. 7.2. author contribution ps, tc and cy conceived and designed the experiment, and defined the intellectual content; tc and ps performed the literature search; tc, ps, jp and pk performed the experiment and collected the data; cj and cy performed the statistical analysis and data interpretation; ps, cj and cy drafted the manuscript. all authors reviewed and approved the final draft of manuscript. 7.3. funding/support none. 7.4. conflict of interest none. references 1. lloyd-jones d, adams r, brown t, carnethon m, dai s, de simone g, et al. american heart association statistics committee and stroke statistics subcommittee. executive summary: heart disease and stroke statistics–2010 update: a report from the american heart association. circulation. 2010;121(7):948-54. 2. mcnally b, robb r, mehta m, vellano k, valderrama al, yoon pw, et al. out-of-hospital cardiac arrest surveillance—cardiac arrest registry to enhance survival (cares), united states, october 1, 2005–december 31, 2010. morbidity and mortality weekly report: surveillance summaries. 2011;60(8):1-19. 3. fairbanks rj, shah mn, lerner eb, ilangovan k, pennington ec, schneider sm. epidemiology and outcomes of out-of-hospital cardiac arrest in rochester, new york. resuscitation. 2007;72(3):415-24. 4. krittayaphong r, 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resuscitation. 2004;61(1):55-61. 18. perkins gd, stephenson bt, smith cm, gao f. a comparison between over-the-head and standard cardiopulthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. supatanakij et al. 6 monary resuscitation. resuscitation. 2004;61(2):155-61. 19. lei z, qing h, yaxiong z. the efficacy of straddling external chest compression on a moving stretcher. resuscitation. 2010;81(11):1562-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e62 rev i ew art i c l e central nervous system complications in covid-19 patients; a systematic review and meta-analysis based on current evidence arian madani neishaboori1, donya moshrefiaraghi1, kosar mohamed ali2, amirmohammad toloui1, mahmoud yousefifard1∗, mostafa hosseini3 † 1. physiology research center, iran university of medical sciences, tehran, iran. 2. college of medicine, university of sulaimani, sulaimani, iraq. 3. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. received: may 2020; accepted: may 2020; published online: 7 june 2020 abstract: introduction: several studies have confirmed neurological involvements, such as acute cerebrovascular disease and impaired consciousness in covid-19. in the present study, our aim is to investigate the current evidence regarding central nervous system (cns) complications in patients with confirmed covid-19. methods: an extensive search was conducted in electronic databases including medline (using pubmed), embase, scopus, and web of science, in addition to the manual search in google and google scholar search engines, for articles published from 2019 until april 21st, 2020. inclusion criteria was articles that were reviewed and reported the incidence of neurological outcomes in patients with confirmed covid-19 disease. results: the initial search yielded 638 records, from which 7 articles were included. overall, the incidence of cns complications was calculated to be 6.27% (95% ci: 3.32 to 9.98). the incidence of the most common cns complications, encephalopathy and acute cerebrovascular disease, were 9.14% (95%ci: 2.20 to 19.81) and 2.59% (95% ci: 1.31 to 4.25), respectively. conclusion: cns complications do exist in covid-19 patients, encephalopathy being the most concerning one. the heterogeneity in the existing literature causes an uncertainty in reporting the definite prevalence rate for each complication. thus, further studies are needed for scientists to reach a more accurate estimate of the prevalence of these complications in covid-19 patients. however, healthcare providers should consider the possibility of cns involvements in patients with sars-cov-2 infection. keywords: covid-19; stroke; prevalence; central nervous system diseases cite this article as: madani neishaboori a, moshrefiaraghi d, mohamed ali k, toloui a, hosseini m, yousefifard m. central nervous system complications in covid-19 patients; a systematic review and meta-analysis based on current evidence. arch acad emerg med. 2020; 8(1): e62. 1. introduction in december 2019, several cases of a severe inexplicable pneumonia emerged in wuhan, china, and all those affected had connections to a local seafood market (1, 2). the etiology of the disease was confirmed to be a novel coronavirus (3). due to the virus’s abysmal similarity to severe acute respira∗corresponding author: mahmoud yousefifard; physiology research center, iran university of medical sciences, hemmat highway, p.o box: 14665-354, tehran, iran; phone/fax: +982186704771; e-mail: yousefifard.m@iums.ac.ir † corresponding author: mostafa hosseini; department of epidemiology and biostatistics school of public health, tehran university of medical sciences, poursina ave, tehran, iran; email: hoseinim@sina.tums.ac.ir; mhossein110@yahoo.com; tel: +982188989125; fax: +982188989127 tory syndrome coronavirus (sars-cov ) in clinical and genotype characteristics, it was named "sars-cov-2" or "severe acute respiratory syndrome coronavirus 2" by world health organization (who) on february 11t h , 2020. at first, an environmental exposure was estimated to be the cause of the disease, but shortly after, with the number of patients rapidly increasing, human to human transmission was confirmed (46). after the disease spread to over 110 countries, who declared a global pandemic on march 11th 2020, and as of that date, the number of covid-19 cases is increasing daily (7). the most common symptoms of the disease are fever, dry cough and dyspnea, in addition to fatigue, sore throat and other non-specific symptoms (6). mostly, patients with diabetes, hypertension, cardiovascular diseases and old age sufthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. madani neishaboori et al. 2 fer from severe type of the disease, and fatality rate is highest amongst these groups of patients (8, 9). moreover, due to the virus’ host cell receptor being abundant in the body, the variety of its symptoms may expand even further. sars-cov-2 exploits the angiotensin converting enzyme 2 (ace-2) receptor, expressed in many organs such as lungs, kidneys and neurological tissue, to enter the cells (10, 11). due to that fact, the presence of ace-2 receptor in neurological tissue may be the reason for sars-cov-2 having the potential to cause central nervous system (cns) symptoms (12). in a retrospective case series conducted by ling mao et al., of 214 hospitalized covid-19 patients in wuhan, the epicenter of disease, 78 patients (36.4%) had developed neurological manifestations. these manifestations included acute cerebrovascular disease and impaired consciousness (13). detailed neurological investigations such as autopsies and attempts to extract sars-cov-2 from cerebrospinal fluid and glial cells in covid-19 patients, have indicated that cerebral involvement alone, can be a reason for the mortality caused by this disease ,due to the potential of causing cerebral edema (14). overall, evidence confirming the presence of neurological involvement in covid-19 do exist, so studies should be focused on illuminating the extent of that association. despite the fact that neurological complications particularly occur in severe forms of the disease (15-17), managing these complications can be vital to overall health and recovery of all covid-19 patients. in this study, our aim is to review the current epidemiological evidence regarding cns complications in patients whose covid-19 infection has been confirmed by definitive laboratory test results. 2. methods 2.1. study design and setting the present systematic review and meta-analysis aims to acquire and analyze evidence regarding cns outcomes in patients with covid-19 disease. pico in the present study is as follows: p: patients with confirmed covid-19, i: report of a neurological outcome, o: prevalence of the reported neurological outcome. due to the purpose of this study, which was only reporting of neurological outcomes in patients with covid-19 disease, no comparison was intended and thus, c in pico was not defined. 2.2. search strategy firstly, several keywords were selected with the advice of experts in the field. afterwards, selected keywords were searched in mesh and emtree to find related synonyms. additionally, titles and abstracts of related articles were screened to find other possible relevant keywords. finally, using the keywords, an extensive search was conducted in electronic databases medline (using pubmed), embase, scopus and web of science, for articles published from 2019 until april 21s t , 2020. search strategy in medline database through pubmed is presented in appendix 1. in addition to the systematic search, manual search was also performed in google and google scholar to find additional, pre-printed manuscripts and possible missing articles. 2.3. selection criteria all articles that reviewed and reported the incidence of neurological outcomes in patients with confirmed covid-19 were included in this review. moreover, the exclusion criteria were case report articles, review articles and studies that only addressed neurological symptoms that cannot be certainly attributed to the involvement of cns (such as general headache) in a covid-19 patient. 2.4. data collection two independent researchers screened titles and abstracts of the articles obtained from searching the databases and gathered full texts of the possibly related studies. next, based on the inclusion and exclusion criteria, articles were chosen and entered to the present systematic review and metaanalysis. afterwards, the useful data of included articles were summarized and recorded. the recorded data included first author’s name, publication year, country in which the study was conducted in, number of patients, study design, number of patients in which the neurological outcome was assessed, mean age of the patients, number of males among the patients, type of reported neurological outcomes, diagnostic method used for recording the outcome, and number of patients presenting with the neurological outcome. since some studies reported more than one neurological outcome, the prevalence rate was evaluated separately for each neurological outcome among the studies, as well as evaluating an overall rate of all neurological outcomes reported in the included studies. any disagreements within the mentioned steps were resolved through discussion with a third reviewer. 2.5. quality assessment since the design of included studies was observational, national heart, lung, and blood institute (nhlbi) quality assessment tool was used to evaluate the risk of bias among studies (18). two independent reviewers assessed the studies and rated the items of the tool based on its key questions and personal judgment. 2.6. statistical analysis analysis was performed in stata 14.0 statistical program. data was recorded as total sample size and frequency of cns complication, and using "metaprop_one" command an overall prevalence with a 95% confidence interval (95% ci) was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e62 table 1: summary of included studies author; year; country study design sample size mean age number of males diagnostic methods type of neurologic manifestation no. of complications chen; 2020; china retrospective 274 62 171 clinical symptom and laboratory findings hypoxic encephalopathy 24 helmes; 2020; france prospective 58 63 nr mri cerebral ischemic stroke 3 mri brain leptomeningeal enhancement 8 clinical symptom encephalopathy 13 clinical symptom dysexecutive syndrome 15 mri brain perfusion abnormalities 11 klok; 2020; netherlands prospective 184 64 139 ct acute cerebrovascular disease 3 li; 2020; china retrospective 221 53.3 131 ct acute cerebrovascular disease 13 lodigiani; 2020; italy retrospective 388 66 264 report of treating physician acute cerebrovascular disease 9 lu; 2020; china retrospective 304 44 182 clinical symptom encephalopathy 8 nr acute cerebrovascular disease 3 mao; 2020; china retrospective 214 52.7 87 ct acute cerebrovascular disease 6 nr ataxia 1 ct: computed tomography scan; mri: magnetic resonance imaging; nr: not reported reported. since, various cns complications were reported in the included studies, we categorized them as acute cerebrovascular disease, brain encephalopathy and other complications (brain leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities and ataxia) and analyses were stratified accordingly. i2 test was used to assess heterogeneity. since considerable heterogeneity was observed, random effect model was adopted to estimate cns complication and its corresponding 95% ci. publication bias was assessed using egger’s test. 3. results 3.1. study characteristics the initial search yielded 638 records, and after eliminating duplicates, 489 records remained. after reviewing the remaining studies, 7 articles were included in the present systematic review and meta-analysis (figure 1) (13, 19-24). 4 studies were conducted in china, and the rest were conducted in france, netherlands, and italy. only two cohort studies were found among the included studies (21, 23), and the rest of the studies were either cross-sectional (20, 22, 24) or case series (1,7). in total, the included studies evaluated neurological outcomes in 1643 covid-19 patients. the mean age of the studies patients ranged from 44 to 66 years old. the number of male patients was not recorded in one study (20); however, among the rest of the included studies, 974 males were studies among the 1585 recruited patients. based on the included studies, encephalopathy was the most common cns complication observed in 3 studies and among 45 covid-19 patients (19, 20, 24), being evaluated based on clinical symptoms. moreover, acute cerebrovascular disease and ischemic stroke was the second most common reported complication in the studies, being reported in 6 studies and 37 patients in total (13, 20-24). however, different studies used various diagnostic techniques to verify the incidence of acute cerebrovascular disease in patients, with computed tomography scan being the most common diagnostic method used. the other reported neurological complications observed following sars-cov-2 infection were brain leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities (20) and ataxia (13). table 1 summarizes characteristics of the 7 studies included in the present analysis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. madani neishaboori et al. 4 table 2: risk of bias assessment of included studies based on nhlbi tools item chen; 2020 helmes; 2020 klok; 2020 li; 2020 lodigiani; 2020 lu; 2020 mao; 2020 criteria 1 © © © © © © © criteria 2 © © © © © © © criteria 3 © © © © © © © criteria 4 © © © © © © © criteria 5 § § § § § § § criteria 6 © © © © © © © criteria 7 § a § § § © § criteria 8 § § § § § § § criteria 9 © © © © © © © criteria 10 na na na na na na na criteria 11 © © © © © a © criteria 12 a a a a a a a criteria 13 © © © © © © © criteria 14 na na na na na na na ©: low risk; §: high risk; a: unclear risk; na: not applicable criteria 1. was the research question or objective in this paper clearly stated? criteria 2. was the study population clearly specified and defined? criteria 3. was the participation rate of eligible persons at least 50%? criteria 4. were all the subjects selected or recruited from the same or similar populations (including the same time period)? were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? criteria 5. was a sample size justification, power description, or variance and effect estimates provided? criteria 6. for the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? criteria 7. was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed? criteria 8. for exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)? criteria 9. were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? criteria 10. was the exposure(s) assessed more than once over time? criteria 11. were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? criteria 12. were the outcome assessors blinded to the exposure status of participants? criteria 13. was loss to follow-up after baseline 20% or less? criteria 14. were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)? 3.2. risk of bias assessment and publication bias no publication bias was observed in the studies reporting cns outcomes based on egger’s test and funnel plot assessment, as presented in figure 2 (acute cerebrovascular disease: p=0.087, encephalopathy: p=0.383, other cns complications: p=0.005). risk of bias assessment of included studies is presented in table 2. sample size justification was not provided in all studies. in addition, timeframe and follow up duration of 5 studies were not sufficient to evaluate association between covid-19 and cns manifestations, as some patients were still hospitalized at the time of analysis. also, the blinding status of outcome assessor was not reported in some the studies. 3.3. meta-analysis cns complications were investigated and analyzed in the included studies, and results of the analysis are presented as a forest plot in figure 3. overall, the incidence of the cns complications was calculated to be 6.27% (95% ci: 3.32 to 9.98) with a considerable heterogeneity observed between the studies as a whole (i2=90.07%). the prevalence of the acute cerebrovascular disease was 2.59% among covid-19 patients (95% ci: 1.31 to 4.25; i2=60.3%). moreover, overall reported incidence of encephalopathy was calculated to be 9.14% (95%ci: 2.20 to 19.81). other cns complications including brain leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities and ataxia were also assessed and their overall incidence was evaluated to be 13.39% (95% ci 0.90 to 35.46; i2=95.3%). 4. discussion the findings of the present systematic review and metaanalysis demonstrated that cns complications definitely exist in covid-19 patients, with an overall prevalence calculated to be 6.27% based on the studies found until april 21s t 2020. in terms of the type of complications, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e62 figure 1: flow diagram of the present meta-analysis. encephalopathy and acute cerebrovascular disease were the most prevalent, and other cns complications including brain leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities and ataxia were also observed among the patients. however, there are a few limitations regarding the reported prevalence. regarding the incidence of encephalopathy, although it was the most prevalent cns complication with respect to the overall number of patients, only three articles reported this complication (19, 20, 24). moreover, the study sample size in the three articles differ, with helmes et al. contemplating on a patient population much less than the other two studies, causing a possible bias in the results of the study. also, helmes et al. studied only a population of severe cases of covid-19 patients, whilst the other two studies contemplated on a spectrum of disease severities among their included study samples. as a result, more studies with larger population and variety in severity of disease among patients are needed to reach a more accurate consensus over the actual prevalence of encephalopathy between covid-19 patients. nonetheless, the possibility of encephalopathy is noticeably high, and thus, healthcare providers should pay extra attention to its presence in patients with covid-19. previously, some case report studies had reported the incidence of encephalopathy as a complication of covid-19 (25-27), and our results have raised more concern over this matter. six studies reported the incidence of acute cerebrovascular disease and stroke in covid-19 patients. however, two studies in this section may be the source of existing heterogeneity (20, 22), reporting a higher than average prevalence for acute cerebrovascular disease and stroke. as previously mentioned, the sample size in helmes et al.’s study is considerably low compared with the other five articles. in addition, concerning other neurological complications, only two studies recorded and reported neurological complications other than acute cerebrovascular disease and encephalopathy (13, 20), so more researches are required to take place to evaluate and assess other types of cns complications in covid-19 patients. 5. conclusion overall, we conclude that cns complications in covid-19 patients do exist. however, with the studies reporting a variety of types of complications, and the focus of the existing studies being mainly on encephalopathy and acute cerebrovascular disease, there is inevitably uncertainty. nonethethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. madani neishaboori et al. 6 figure 2: funnel plot for assessment of publication bias in central nervous system (cns) complications following sars-cov2 infection. other complications: brain leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities, ataxia. less, our results have emphasized that sars-cov-2 may damage the cns while infecting its host (28, 29). in this regard, healthcare providers should take extra care with their covid-19 patients presenting with symptoms indicative of cns complications. 6. declarations 6.1. acknowledgements none. 6.2. authors contributions study design: my, amn; data gathering: dm, at, amn; analysis: my; drafting: amn; critically revised: all authors authors orcids arian madani neishaboori: 0000-0002-1920-9299 donya moshrefiaraghi: 0000-0002-5282-8825 kosar mohamed ali: 0000-0001-5533-2924 amirmohammad toloui: 0000-0002-9809-0985 mahmoud yousefifard: 0000-0001-5181-4985 6.3. funding support none. 6.4. conflict of interest there is no conflict of interest. references 1. wang c, horby pw, hayden fg, gao gf. a novel coronavirus outbreak of global health concern. the lancet. 2020;395(10223):470-3. 2. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e62 figure 3: forest plot for prevalence of central nervous system (cns) complication following sars-cov-2 infection. the overall prevalence of cns complication was 6.27%. other complications: brain leptomeningeal enhancement; dysexecutive syndrome; brain perfusion abnormalities; ataxia. 3. zhu n, zhang d, wang w, li x, yang b, song j, et al. china novel coronavirus investigating and research team. a novel coronavirus from patients with pneumonia in china, 2019. n engl j med. 2020;382(8):727-33. 4. chan jf-w, yuan s, kok k-h, to kk-w, chu h, yang j, et al. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet. 2020;395(10223):514-23. 5. wang d, hu b, hu c, zhu f, liu x, zhang j, et al. clinical 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creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e62 appendix 1: medline search query 1. "betacoronavirus"[mh] or "coronavirus"[mh] or "coronavirus infections"[mh] or "covid-19 vaccine"[supplementary concept] or "covid-19 diagnostic testing"[supplementary concept] or 2019 novel coronavirus disease[tiab] or covid19[tiab] or covid-19[tiab] or sars-cov-2[tiab] or covid-19 pandemic[tiab] or sars-cov-2 infection[tiab] or covid-19 virus disease[tiab] or 2019 novel coronavirus infection[tiab] or 2019-ncov infection[tiab] or coronavirus disease 2019[tiab] or coronavirus disease-19[tiab] or 2019-ncov disease[tiab] or covid-19 virus infection[tiab] or severe acute respiratory syndrome coronavirus 2[tiab] 2. "stroke"[mh] or "cerebrovascular disorders"[mh] or "brain ischemia"[mh] or "encephalitis"[mh] or "infectious encephalitis"[mh] or "encephalitis, viral"[mh] or "encephalitis viruses"[mh] or "meningitis"[mh] or "meningitis, viral"[mh] or "central nervous system infections"[mh] or "central nervous system viral diseases"[mh] or "nervous system diseases"[mh] or "central nervous system diseases"[mh] or "neurologic manifestations"[mh] or "brain"[mh] or "brain infarction"[mh] or stroke[tiab] or strokes[tiab] or cerebrovascular accident[tiab] or cerebrovascular accidents[tiab] or cva (cerebrovascular accident)[tiab] or cvas (cerebrovascular accident)[tiab] or cerebrovascular apoplexy[tiab] or apoplexy, cerebrovascular[tiab] or vascular accident, brain[tiab] or brain vascular accident[tiab] or brain vascular accidents[tiab] or vascular accidents, brain[tiab] or cerebrovascular stroke[tiab] or cerebrovascular strokes[tiab] or stroke, cerebrovascular[tiab] or strokes, cerebrovascular[tiab] or apoplexy[tiab] or cerebral stroke[tiab] or cerebral strokes[tiab] or stroke, cerebral[tiab] or strokes, cerebral[tiab] or stroke, acute[tiab] or acute stroke[tiab] or acute strokes[tiab] or strokes, acute[tiab] or cerebrovascular accident, acute[tiab] or acute cerebrovascular accident[tiab] or acute cerebrovascular accidents[tiab] or cerebrovascular accidents, acute[tiab] or brain infarction[tiab] or brain infarctions[tiab] or infarction, brain[tiab] or infarctions, brain[tiab] or brain infarct[tiab] or brain infarcts[tiab] or infarct, brain[tiab] or infarcts, brain[tiab] or anterior circulation brain infarction[tiab] or infarction, brain, anterior circulation[tiab] or infarction, anterior circulation, brain[tiab] or anterior circulation infarction, brain[tiab] or brain infarction, anterior circulation[tiab] or venous infarction, brain[tiab] or brain venous infarction[tiab] or brain venous infarctions[tiab] or infarction, brain venous[tiab] or infarctions, brain venous[tiab] or venous infarctions, brain[tiab] or brain infarction, venous[tiab] or brain infarctions, venous[tiab] or infarction, venous brain[tiab] or infarctions, venous brain[tiab] or venous brain infarction[tiab] or venous brain infarctions[tiab] or anterior cerebral circulation infarction[tiab] or infarction, anterior cerebral circulation[tiab] or brain infarction, posterior circulation[tiab] or posterior circulation infarction, brain[tiab] or posterior circulation brain infarction[tiab] or infarction, brain, posterior circulation[tiab] or infarction, posterior circulation, brain[tiab] or cerebrovascular disorders[tiab] or cerebrovascular disorder[tiab] or vascular diseases, intracranial[tiab] or intracranial vascular disease[tiab] or intracranial vascular diseases[tiab] or vascular disease, intracranial[tiab] or intracranial vascular disorders[tiab] or intracranial vascular disorder[tiab] or vascular disorder, intracranial[tiab] or vascular disorders, intracranial[tiab] or cerebrovascular diseases[tiab] or cerebrovascular disease[tiab] or disease, cerebrovascular[tiab] or diseases, cerebrovascular[tiab] or brain vascular disorders[tiab] or brain vascular disorder[tiab] or vascular disorder, brain[tiab] or vascular disorders, brain[tiab] or cerebrovascular occlusion[tiab] or cerebrovascular occlusions[tiab] or occlusion, cerebrovascular[tiab] or occlusions, cerebrovascular[tiab] or cerebrovascular insufficiency[tiab] or cerebrovascular insufficiencies[tiab] or insufficiencies, cerebrovascular[tiab] or insufficiency, cerebrovascular[tiab] or brain ischemia[tiab] or brain ischemias[tiab] or ischemia, brain[tiab] or ischemic encephalopathy[tiab] or encephalopathy, ischemic[tiab] or ischemic encephalopathies[tiab] or cerebral ischemia[tiab] or cerebral ischemias[tiab] or ischemias, cerebral[tiab] or ischemia, cerebral[tiab] or encephalitis[tiab] or brain inflammation[tiab] or inflammation, brain[tiab] or brain inflammations[tiab] or rasmussen syndrome[tiab] or rasmussen encephalitis[tiab] or rasmussen’s syndrome[tiab] or encephalitis, rasmussen[tiab] or infectious encephalitis[tiab] or encephalitis, infectious[tiab] or encephalitis infection[tiab] or encephalitis infections[tiab] or infection, encephalitis[tiab] or infections, encephalitis[tiab] or encephalitis, viral[tiab] or encephalomyelitis, infectious, viral[tiab] or infectious encephalomyelitis, viral[tiab] or encephalomyelitis, viral infectious[tiab] or viral infectious encephalomyelitis[tiab] or viral encephalitis[tiab] or encephalitis viruses[tiab] or viruses, encephalitis[tiab] or encephalitis virus[tiab] or virus, encephalitis[tiab] or meningitis[tiab] or meningitides[tiab] or pachymeningitis[tiab] or pachymeningitides[tiab] or meningitis, viral[tiab] or meningitides, viral[tiab] or viral meningitides[tiab] or viral meningitis[tiab] or central nervous system infections[tiab] or infections, central nervous system[tiab] or cns infections[tiab] or cns infection[tiab] or infection, cns[tiab] or infections, cns[tiab] or central nervous system infection[tiab] or central nervous system viral diseases[tiab] or viral diseases, central nervous system[tiab] or viral infections, central nervous system[tiab] or infections, cns, viral[tiab] or infections, viral cns[tiab] or cns infection, viral[tiab] or cns infections, viral[tiab] or infection, viral cns[tiab] or viral cns infection[tiab] or viral cns infections[tiab] or cns viral diseases[tiab] or cns viral disease[tiab] or disease, cns viral[tiab] or diseases, cns viral[tiab] or viral disease, cns[tiab] or viral diseases, cns[tiab] or central nervous system viral infections[tiab] or nervous system diseases[tiab] or disease, nervous system[tiab] or diseases, nervous system[tiab] or nervous system disease[tiab] or neurologic disorders[tiab] or disorder, neurologic[tiab] or disorders, neurologic[tiab] or neurologic disorder[tiab] or neurological disorders[tiab] or disorder, neurological[tiab] or disorders, neurological[tiab] or neurological disorder[tiab] or nervous system disorders[tiab] or disorder, nervous system[tiab] or disorders, nervous system[tiab] or nervous system disorder[tiab] or central nervous system diseases[tiab] or central nervous system disorders[tiab] or cns diseases[tiab] or cns disease[tiab] or neurologic manifestations[tiab] or manifestation, neurologic[tiab] or neurological manifestations[tiab] or neurologic manifestation[tiab] or neurologic signs and symptoms[tiab] or manifestations, neurologic[tiab] or manifestations, neurological[tiab] or manifestation, neurological[tiab] or neurological manifestation[tiab] or neurologic deficits[tiab] or deficit, neurologic[tiab] or deficits, neurologic[tiab] or neurologic deficit[tiab] or neurologic symptoms[tiab] or neurologic symptom[tiab] or symptom, neurologic[tiab] or symptoms, neurologic[tiab] or neurologic findings[tiab] or finding, neurologic[tiab] or findings, neurologic[tiab] or neurologic finding[tiab] or neurologic signs[tiab] or neurologic sign[tiab] or sign, neurologic[tiab] or signs, neurologic[tiab] or focal neurologic deficits[tiab] or deficit, focal neurologic[tiab] or deficits, focal neurologic[tiab] or focal neurologic deficit[tiab] or neurologic deficit, focal[tiab] or neurologic deficits, focal[tiab] or neurologic dysfunction[tiab] or dysfunction, neurologic[tiab] or dysfunctions, neurologic[tiab] or neurologic dysfunctions[tiab] or encephalopathy[tiab] or clinical characteristics[tiab] or brain[tiab] 3. #1 and #2 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion conclusion declarations references emergency. 2018; 6 (1): e30 or i g i n a l re s e a rc h epidemiology and outcome of patients with acute kidney injury in emergency department; a cross-sectional study saeed safari1, behrouz hashemi1, mohammad mehdi forouzanfar1, mehrnoush shahhoseini1, meysam heidari1∗ 1. emergency department, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: april 2018; accepted: may 2018; published online: 5 may 2018 abstract: introduction: elimination of preventable deaths due to acute kidney injury (aki) in low-income countries by 2025 is an important healthcare goal at the international level. the present study was designed with the aim of evaluating the prevalence and outcome of aki in patients presenting to emergency department. methods: the present cross-sectional, retrospective study was performed on patients that presented to the emergency departments of 3 major teaching hospitals, tehran, iran, between 2005 and 2015 and were diagnosed with aki. patient selection was done using consecutive sampling and required data for this study was extracted by referring to the medical profiles of the patients and filling out a checklist designed for the study. results: 770 aki patients with the mean age of 62.72 ± 19.79 (1 – 99) years were evaluation (59.1% male). 690 (89.61%) cases of aki causes were pre-renal or renal. among the pre-renal causes, 74 (73.3%) cases were due to different types of shock (p < 0.001). the most common etiologic causes of aki in pre-renal group were hypotension (57.3%) and renal vascular insufficiency (31.6%). in addition, regarding the renal types, rhabdomyolysis (35.0%), medication (17.5%) and chemotherapy (15.3%) and in post-renal types, kidney stone (34.5%) were the most common etiologic causes. 327 (42.5%) patients needed dialysis and 169 (21.9%) patients died. sex (p = 0.001), age over 60 years (p = 0.001), blood urea nitrogen level (p < 0.001), hyperkalemia (p < 0.001), metabolic acidosis (p < 0.001), cause of failure (p = 0.001), and type of failure (p = 0.009) were independent risk factors of mortality. conclusion: the total prevalence of aki in emergency department was 315 for each 1000000 population and preventable mortality rate due to aki was estimated to be 28.2 cases in each 1000000 population. the most important preventable aki causes in the pre-renal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. keywords: acute kidney injury; outcome assessment (health care); prevalence; epidemiology; renal insufficiency © copyright (2018) shahid beheshti university of medical sciences cite this article as: safari s, hashemi b, forouzanfar m, shahhoseini m, heidari m. epidemiology and outcome of patients with acute kidney injury in emergency department; a cross-sectional study. emergency. 2018; 6(1): e30. 1. introduction a cute kidney injury (aki), which was called acute renal failure in the past, is defined as sudden failure and inefficiency of the kidney (1). this disease is one of the most important causes of mortality in hospitalized patients and with aging of the population and based on new definitions, the number of those affected with it has increased (25). annual prevalence of patients with aki in need of one of the replacement methods has been reported to be about 200 ∗corresponding author: meysam heidari; emergency department, shohadaye tajrish hospital,shahrdari avenue, tajrish square, tehran, iran. tel: +989121778121 email: dr.meysamheydari@yahoo.com to 300 cases in 1 million population (6, 7). the causes of aki are different based on various geographical regions and there is a significant difference in its prevalence between developing and developed countries (8). most affected population is 60 – 79 year old men and common comorbidities in this group of patients include surgery, diabetes, pneumonia, cardiac failure, stroke, and history of chronic kidney disease (9). currently, the universal policy and the international society of nephrology (isn) policy are concentrated on elimination of preventable deaths due to aki in low-income countries by 2025 (10). for effective planning regarding reduction of preventable mortalities resulting from aki there is a need for sufficient data regarding the epidemiologic pattern of this disease in each country. various reports have been published in this this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 2 regard until now but most studies have been restricted to cases after surgery or in the intensive care unit (icu) and have somehow covered the aki cases initiated in the hospital (11, 12). therefore, the present study was done with the aim of evaluating the prevalence and outcome of aki in patients presenting to emergency department as a sample of community acquired cases. 2. methods 2.1. study design and setting the present cross-sectional retrospective study was performed on patients that presented to the emergency departments of teaching hospitals of shahid beheshti university of medical sciences (imam hossein, loghmane hakim and shohadaye tajrish), tehran, iran, between 2005 and 2015 and were diagnosed with aki. these 3 hospitals are major hospitals and referral centers and bear the treatment burden of about one third of the patients in tehran and its suburbs with a population of about 14 million people. protocol of the study was approved by the ethics committee of shahid beheshti university of medical sciences and the researchers adhered to confidentiality of patients’ data and the recommendations in the declaration of helsinki throughout the study. 2.2. participants all the patients who were hospitalized in the emergency departments of the mentioned hospitals during the studied years were evaluated via consecutive sampling. patients who had kidney transplants or were under treatment with one of the renal replacement therapy (rrt) methods including blood or peritoneal dialysis were excluded from the study. in addition, patients with a missing data regarding the confirmed diagnosis or the etiologic causes of aki were also excluded from the study. no age or sex limitations were considered for the present study. 2.3. data gathering data required for the present study was gathered by referring to the medical profiles of the patients and by filling out a checklist designed for the study. for this purpose, by referring to the medical document registry center of the mentioned hospitals, the list of patients who had been hospitalized via the emergency department with diagnosis of aki alone or along with other diagnoses were extracted. then, using the identification number of each patient, their clinical profile was extracted from the archive and a trained senior emergency medicine resident studied the profile and extracted the data by consulting an emergency medicine specialist. the checklist used in the present study included demotable 1: baseline characteristics of the studied patients variable frequency (%) sex male 455 (59.1) female 315 (40.9) age (year) 1 – 19.9 17 (2.2) 20 – 39.9 100 (13.0) 40 – 59.9 176 (22.9) ≤ 60 47 (61.9) underlying illness hypertension 352 (45.7) diabetes 126 (16.4) cardiovascular disease 51 (6.6) malignancy 44 (5.7) other 197 (25.6) cause of failure pre-renal 386 (40.1) renal 304 (39.5) post-renal 87 (11.3) type of failure acute 640 (83.1) acute on top of chronic 130 (16.9) graphic data (age, sex), underlying illnesses, laboratory findings (urea, creatinine, blood urea nitrogen, potassium, blood gas analyses, urinalysis), ultrasonography findings, causes of failure (pre-renal, renal, post renal), type of failure (acute, acute on chronic), etiologic cause of the failure, and the final outcome of the patients (mortality, need for dialysis). diagnosis of aki and its cause was made by a nephrologist in charge of the patient at the time of hospitalization and by considering the existing standard definitions. etiologic causes that led to aki via deficiencies in blood flow to the kidney (shock, vascular deficiencies, dehydration and . . . ) were classified in the pre-renal group, causes that acted via injury to the renal tissue (radio-contrast agents, medications, rhabdomyolysis and . . . ) were in the renal group and finally, causes that resulted in aki via creating an obstacle to evacuation of urine (stone, tumor,. . . ) were placed in the post-renal group. 2.4. statistical analysis samples were gathered via census sampling. all analyses were done using spss 21.0 statistical software. to describe data, frequency and percentage or mean ± standard deviation were used. for comparisons, chi square, or fisher’s exact statistical tests as well as student t-test were used. for multivariate analysis, logistic regression analysis was applied. in all comparisons, p less than 0.05 was considered as level of significance. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e30 figure 1: frequency of acute kidney injury etiology based on pre-renal, renal, and post-renal causes. bph: benign prostatic hyperplasia. 3. results 3.1. baseline characteristics 770 aki patients with the mean age of 62.72 ± 19.79 (1 – 99) years were studied (59.1% male). table 1 depicts the baseline characteristics of the studied patients. 477 (61.9%) patients were in the age group of ≥60 years and hypertension was their most common underlying disease (45.7%). considering the presentation of about 2,444,000 individuals to the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 4 emergency departments of the studied hospitals during the mentioned period, prevalence of aki was estimated as 315 in 1000000 population. 3.2. laboratory data mean blood urea nitrogen and creatinine of the patients were 81.57 ± 57.75 (20 – 590) mg/dl and 3.50 ± 2.20 (1.5 – 20.1) mg/dl, respectively. hyperkalemia was reported in 106 (13.8%) and metabolic acidosis in 233 (30.3%) patients. the results of urinalysis was available for 520 patients, which indicated 14 (1.8%) cases of > 50 red blood cells, 40 (5.2%) blood positive cases, 29 (3.8%) cases of high white blood cells, 59 (7.7%) protein positive cases, 27 (3.5%) cast positive cases, 40 (5.2%) ketone positive cases, and 23 (3.0%) bacteria positive cases. 3.3. ultrasonography findings kidney ultrasonography findings were available for 664 of the studied patients. regarding the size of the kidney, 472 (70.9%) cases were normal, 110 (16.5%) were atrophic, and 84 (12.6%) cases of hydronephrosis were reported. other ultrasonography findings consisted of 60 (9.0%) cases of simple cysts, 41 (6.2%) cases of stone, and 28 (4.2%) calcification. 3.4. etiologic causes 690 (89.61%) cases of aki were pre-renal or renal (table 1). figure 1 shows the frequency of etiologic causes of aki based on types of pre-renal, renal, and post-renal. among the prerenal causes, 74 (73.3%) cases were due to different types of shock (p < 0.001). the most common etiologic causes of aki in pre-renal group were hypotension (57.3%) and failure of renal vessels (31.6%). in addition, regarding the renal types, rhabdomyolysis (35.0%), medication (17.5%) and chemotherapy (15.3%) and in post-renal types, kidney stone (34.5%) were the most common etiologic causes. 3.5. patient outcome in the end, 327 (42.5%) patients needed dialysis 167 (51.2%) of which underwent dialysis once, 79 (24.2%) twice, 44 (13.5%) 3 times, and 36 (11.1%) underwent dialysis 4 times or more. 169 (21.9%) patients died, in 69 (8.9%) cases the cause of death was diagnosed due to aki. in other words, by preventing aki, 8.9% of mortalities were preventable. 3.6. factors related to mortality table 2 has evaluated the correlation of various factors with mortality. the rate of mortality in patients significantly correlated with sex (p = 0.001), age over 60 years (p = 0.027), hyperkalemia (p < 0.001), metabolic acidosis (p < 0.001), the cause of failure (p < 0.001), need for dialysis (p = 0.031), and type of failure (p = 0.014). dead patients had significantly higher serum creatinine levels (4.14 ± 2.60 vs. 3.32 ± 2.03 mg/dl; p<0.001) and blood urea nitrogen (99.56 ± 74.30 vs. 76.51 ±51.11 mg/dl; p<0.001). the results of multivariate analysis was indicative of the significant and independent correlation of sex (p = 0.001), age over 60 years (p = 0.001), blood urea nitrogen level (p < 0.001), hyperkalemia (p < 0.001), metabolic acidosis (p < 0.001), cause of failure (p = 0.001), and finally, type of failure (p = 0.009) with mortality. 4. discussion based on the findings of the present study, the total prevalence of aki in patients presenting to the emergency departments of the evaluated hospitals was 315 for each 1000000 population and preventable mortality rate due to aki was estimated to be 28.2 cases in each 1000000 population. the most important preventable aki cases in the pre-renal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. hoste et al. in a study in 2006 emphasized that even little changes in renal functionality of the hospitalized patients can have adverse effects on their final outcome (13). the results of studies show that patients with aki who need dialysis are in higher risk for chronic kidney failure and permanent need for dialysis (14, 15). the prevalence of aki is widely different among various studies and from 1811 to 3000 individuals in 1 million has been reported among hospitalized patients (2, 16). of course, this rate has been reported much higher in critically ill patients. the results of the study by hoste et al. are indicative of 67.2% prevalence of aki in critically ill patients hospitalized in icu (17). additionally, ralib et al. in addition to confirming the findings of the mentioned study showed that 60% of aki cases in critically ill patients happen in the initial 48 hours of their hospitalization in icu (18). the results of a study in iran was indicative of the exceptionally high prevalence of 49.1% of aki and 2.7% mortality due to it following open heart surgery (19). the reason for the low prevalence found in this study might be the research environment. because emergency department patients can be considered as a sample of community acquired aki cases and not imposed by hospitalization and etc. therefore, considering this point, the low prevalence obtained can be explained. based on the results of the present study, more than 80% of aki cases had happened in individuals over 50 years of age, which is in line with the findings of previous studies in this regard (2, 3). in the present study, hypertension and diabetes were the most common comorbidities of aki (62.1%). in addition, pre-renal types with 40.1% prevalence were the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e30 table 2: correlation of different factors with mortality variable dead alive p value sex male 119 (26.2) 336 (73.8) <0.001 female 50 (15.8) 265 (84.2) age < 60 52 (17.7) 241 (82.3) 0.027 ≤ 60 117 (24.5) 360 (75.5) ultrasonographic size of kidney normal 98 (20.8) 374 (79.2) atrophic 23 (20.9) 87 (79.1) 0.051 hypertrophic 8 (9.5) 76 (90.5) hyperkalemia yes 43 (40.6) 63 (59.4) < 0.001 no 126 (19.0) 538 (81.0) metabolic acidosis yes 82 (35.2) 151 (64.8) < 0.001 no 87 (16.2) 450 (83.8) cause of failure pre-renal 99 (26.1) 280 (73.9) renal 68 (22.4) 236 (77.6) < 0.001 post-renal 2 (2.3) 85 (97.7) type of failure acute 151 (23.6) 489 (76.4) 0.014 acute on top of chronic 18 (13.8) 112 (86.2) need for dialysis yes 84 (25.7) 243 (74.3) 0.031 no 85 (19.2) 387 (80.8) number of dialysis sessions < 3 times 62 (25.2) 184 (74.8) 0.852 ≥ 3 times 21 (26.2) 59 (73.8) most frequent and the most common cause of them was reported as various types of shock. chertow et al. epidemiologically evaluated patients with aki and introduced decreased blood flow to the kidney, major surgeries, and injection of radio-contrast as important factors related to different types of pre-renal failures (20). although many studies have been done on the epidemiology of aki in different places all over the world, due to the differences present in the definitions of aki as well as different environments we have seen dissimilar reports regarding the prevalence and outcome of these patients. additionally, the etiologic causes of aki vary in different countries. for these reasons, it seems that different countries should do their own studies on the burden of this disease in their country to be able to act towards preventing the disease by identifying the causes. based on the results of this study and as might have been predicted before, the pre-renal and renal causes were at the top of the causes of failure. modification of lifestyle and reducing the burden of non-communicable chronic diseases such as hypertension, diabetes, dyslipidemia and . . . can result in reduction in the prevalence of a major part of pre-renal cases by decreasing the prevalence of vascular diseases. in addition, with aging of the population and increase in prevalence of diseases such as sepsis in these ages, more attention should be paid regarding dehydration and prevention of septic shock occurrence in these patients. more care should be taken regarding the use of nephrotoxic agents such as radiocontrasts as well as traumatic rhabdomyolysis, which is very important due to iran being affected with many natural disasters and traffic accidents (21-25). it seems that by performing a multi-center study around iran and identifying preventable causes of aki and increasing public awareness in this regard, we can take a big step towards improving public health and decreasing the burden of aki. 5. limitation missing data in some profiles and not being able to contact patients for follow-up of treatment process as well as limited sample size are among the limitations of this study. definition of aki and its causes were recorded based on the opinion of the nephrologist in charge of the patient and therefore, this can impair the results to some extent. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. safari et al. 6 6. conclusion based on the findings of the present study, the total prevalence of aki in patients presenting to the emergency departments of the evaluated hospitals was 315 for each 1000000 population and preventable mortality rate due to aki was estimated to be 28.2 cases in each 1000000 population. in addition, the most important preventable aki cases in the prerenal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. 7. appendix 7.1. acknowledgements the present article is derived from dr. meysam heydariâăźs thesis for receiving his specialist degree in emergency medicine, performed under supervision of dr. saeed safari. 7.2. author contribution all the authors met the 4 criteria recommended by the international committee of medical journal editors for gaining authorship. 7.3. funding/support none. 7.4. conflict of interest none. references 1. webb s, dobb g. arf, atn or aki? it’s now acute kidney injury. anaesthesia and intensive care. 2007;35(6):843-4. 2. ali t, khan i, simpson w, prescott g, townend j, smith w, et al. incidence and outcomes in acute kidney injury: a comprehensive population-based study. journal of the american society of nephrology. 2007;18(4):1292-8. 3. ali t, roderick p. epidemiology of acute kidney injury. in: jãűrres a, ronco c, kellum ja, editors. management of acute kidney problems. berlin, heidelberg: springer berlin heidelberg; 2010. p. 63-73. 4. bagshaw sm, george c, bellomo r. changes in the incidence and outcome for early acute kidney injury in a cohort of australian intensive care units. critical care. 2007;11(3):r68. 5. lameire n, van biesen w, vanholder r. the changing epidemiology of acute renal failure. nature clinical practice nephrology. 2006;2:364. 6. metcalfe w, on behalf of the scottish renal r, simpson m, on behalf of the scottish renal r, khan ih, on behalf of the scottish renal r, et al. acute renal failure requiring renal replacement therapy: incidence and outcome. qjm: an international journal of medicine. 2002;95(9):579-83. 7. hoste ea, schurgers m. epidemiology of acute kidney injury: how big is the problem? critical care medicine. 2008;36(4):s146-s51. 8. susantitaphong p, cruz dn, cerda j, abulfaraj m, alqahtani f, koulouridis i, et al. world incidence of aki: a meta-analysis. clinical journal of the american society of nephrology. 2013;8(9):1482-93. 9. xu x, 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surgery. journal of isfahan medical school. 2013;31(251). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e30 20. chertow gm, burdick e, honour m, bonventre jv, bates dw. acute kidney injury, mortality, length of stay, and costs in hospitalized patients. journal of the american society of nephrology. 2005;16(11):3365-70. 21. iraj n, saeed s, mostafa h, houshang s, ali s, farin rf, et al. prophylactic fluid therapy in crushed victims of bam earthquake. the american journal of emergency medicine. 2011;29(7):738-42. 22. safari s, najafi i, hosseini m. outcomes of fasciotomy in patients with crush-induced acute kidney injury after bam earthquake. iranian journal of kidney diseases. 2011;5(1):25. 23. hosseini m, safari s, sharifi a, amini m, farokhi fr, sanadgol h, et al. wide spectrum of traumatic rhabdomyolysis in earthquake victims. acta medica iranica. 2009;47(6):459-64. 24. hashemi b, safari s, hosseini m, yousefifard m, erfani e, baratloo a, et al. a systematic review of iranian experiences in seismo-nephrology. archives of trauma research. 2016;5(2):e28796. 25. safari s, yousefifard m, hashemi b, baratloo a, forouzanfar mm, rahmati f, et al. the role of scoring systems and urine dipstick in prediction of rhabdomyolysis-induced acute kidney injury a systematic review. 2016;10(3):101. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e75 rev i ew art i c l e the prognostic value of thrombocytopenia in covid-19 patients; a systematic review and meta-analysis davood bashash1∗, fatemeh sadat hosseini-baharanchi2, mostafa rezaie-tavirani3, majid safa4, nader akbari dilmaghani 5,6, mohammad faranoush 7, hassan abolghasemi8 1. department of hematology and blood banking, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. minimally invasive surgery research center & department of biostatistics, school of public health, iran university of medical sciences, tehran, iran. 3. proteomics research center, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 4. department of hematology and blood banking, faculty of allied medicine, iran university of medical sciences, tehran, iran. 5. hearing disorders research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. 6. department of otolaryngology, head and neck surgery, loghman hakim educational hospital, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 7. pediatric growth and development research center, institute of endocrinology, iran university of medical sciences, tehran, iran. 8. pediatric congenital hematologic disorders research center, shahid beheshti university of medical sciences, tehran, iran. received: august 2020; accepted: august 2020; published online: 19 september 2020 abstract: introduction: multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in covid-19, we performed a metaanalysis of pertinent literature. method: the keywords "platelet" or "thrombocytopenia" and "covid-19" or "coronavirus 2019" or "2019-ncov" or "sars-cov-2" were searched in national library of medicine medline/pubmed and scopus between december 30, 2019, and may 9, 2020 in english without any restriction. the initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated deïňąnition of covid-19 severity were ïňąnally selected. to assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. also, the heterogeneity among the included studies was tested using the chisquare test. results: the results of our meta-analysis of 19 studies, totaling 3383 covid-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 ci: -31.57, -11.43). conclusion: decreased number of platelets more commonly associates with severe covid-19; however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate. keywords: sars-cov-2; covid-19; prognosis; blood platelets; thrombocytopenia; meta-analysis cite this article as: bashash d, hosseini-baharanchi f s, rezaie-tavirani m, safa m, akbari dilmaghani n, faranoush m, abolghasemi h. the prognostic value of thrombocytopenia in covid-19 patients; a systematic review and meta-analysis. arch acad emerg med. 2020; 8(1): e75. ∗corresponding author: davood bashash; department of hematology and blood banking, school of allied medical sciences, shahid beheshti university of medical sciences, tehran, iran. tel: +98-21-22717504, fax: +98-2122721150, e-mail: d.bashash@sbmu.ac.ir 1. introduction since early 2020, almost all people around the world have been tracking the statistics of the novel coronavirus (2019ncov; named sars-cov-2 by the world health organization (who) in february, 2020 (1)) daily, watching the numbers of infected cases and death tolls increase unceasingly day after day. life is on hold as death and disease have cast this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. bashash et al. 2 a sinister shadow on people’s lives. it is heartbreaking for the generation in their last decades to die alone and also painful for families losing their loved ones. for the time being (i.e. may 11, 2020), over 4,250,000 infected cases with sorrowful statistics of more than 2850,000 deaths have been recorded all over the world. there are also evidence that adults under the indicated age range with no history of medical conditions may display serious complications and present disease with an unfavorable outcome (2). in other words, coronavirus disease 2019 (abbreviated to covid-19) is quite eerie, symptomatically, as patients with sars-cov-2 infection display a wide range of symptoms âăş ranging from mild signs to critical care condition requiring specialized management in intensive care units (icu) (3). although sars-cov-2 has a lower mortality rate compared to severe acute respiratory syndrome (sars)-cov (10%) (4) and middle east respiratory syndrome (mers)-cov (37%) (5), it has killed a shocking, and of course increasing, number of patients and still continues to infect and take its toll (6). multiple lines of evidence have attested that viral infections coincide with platelet activation, either through a direct or indirect manner, contributing to increased consumption of these cells (7). it has also been reported that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases, including rapidly evolving β-coronaviruses (8), and covid-19 shall not be considered an exception to this rule (9). taking advantage of this fact and bearing in mind that the results of several studies reported that low platelet count is associated with increased risk of severe disease (9, 10), it is reasonable to assume that thrombocytopenic covid-19 patients will experience disease with a higher risk of adverse outcome. to provide a well-conceptualized viewpoint demonstrating the prognostic value of platelet count in sars-cov-2 infection, we performed a meta-analysis of pertinent literature to evaluate whether the emergence of thrombocytopenia could discriminate between severe and non-severe cases. 2. method the prisma guideline was used to pertain to the necessities of performing a systematic review and meta-analysis (11). the search strategy was as follows: the keywords "platelet" or "thrombocytopenia" and "covid-19" or "coronavirus 2019" or "2019-ncov" or "sarscov-2" were searched in national library of medicine medline/pubmed and scopus to find articles published between december 30, 2019, and may 9, 2020. the query of ((platelet[title/abstract]) or (thrombocytopenia[title/abstract])) and ((covid-19[title/abstract]) or (coronavirus 2019[title/abstract]) or (2019ncov[title/abstract]) or (sars-cov-2[title/abstract])) was searched in pubmed in english without any restriction about study type. the results of the initial search were first screened by title and abstract, and then full texts of relevant articles were selected. to strengthen the analysis, the reference list of relevant documents was also scrutinized. all the letters, reviews, editorials, case reports, comments, guidelines, and books were excluded. in addition, all articles that neither presented the information on platelet count nor provided data in the severe and non-severe covid-19 cases were excluded. the evidence-based librarianship (ebl) critical appraisal checklist was used to assess the eligibility and quality of the studies. studies with a score higher than 75% were included (12). ms and fh scored the checklist independently, and in the case of disagreement, db made the final decision. meta-analysis was conducted on the mean ± sd platelet counts reported in the included studies to calculate the pooled mean difference in platelet count between severe and non-severe patients. to assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. in case of bias, the random effect model would be fitted (13). the presence of heterogeneity among the included studies was tested using the chi-square test, with the significance level of 0.1. after combining results, the level of heterogeneity based on the i2 statistic was categorized as follows: low > 25%, moderate > 50, and high > 75% (14). a random-effect model was used to take the study-to-study variability into account. statistical significance was set to 0.05. the meta set command in stata was used for meta-analysis. 3. results overall, 4935 articles were identified in our initial search using the indicated criteria and inspecting the reference lists, with a total of 4916 articles being excluded, including 1342 letters, 610 reviews, 418 editorials, 210 case reports, 190 comments, 10 guidelines, and 2 books. the aforementioned articles and also others that either did not fulfill information on the platelet count or provided incomplete information were excluded (2134 articles). the main features of the selected studies including country/city, sample size, and their definition of severe cases are summarized in table 1. in addition, as represented in this table, demographic characteristics (sample size, age, and sex) of both severe and non-severe covid-19 patients were collected for all the included studies. on aggregate, we analyzed the results of the platelet count of a total of 3383 patients, 744 (21.9%) of whom were cases with severe disease. the number of cases ranged between 18-1099, whilst the number of severe cases __though with different definitions__ varied between 6-173. the results of platelet count for both severe and non-severe covidthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e75 table 1: main features of the selected studies study country, city sample size severity definition severe patients non-severe patients n, % age, years female, % n, % age, years female, % huang et al. (24) china, wuhan 41 icu admission 13 (31.7) 49 (41, 61) 2(15) 28(68.3) 49 (41, 57.5) 9 (32) cao et al. (28) china, shanghai 198 icu admission 19 (9.6) 63.7 (16.8) 2 (10.5) 179 (90.4) 48.6 (15.6) 95 (53.1) zhang et al. (29) china, wuhan 221 who guideline (30) 55 (24.9) 62 (52-74) 20 (36.4) 166 (75.1) 51 (36-64.3) 93 (56) wan et al. (31) china, chongqing 135 icu admission; m. ventilation 40 (29.6) 56 (52-73) 19 (47.5) 95 (70.4) 44 (33-49) 43 (45.3) wang et al. (32) china, wuhan 138 icu admission 36 (26.1) 66 (57-78) 14 (38.9) 102 (73.9) 51 (37-62) 49 (48) zhou et al. (33) china, wuhan 191 death 54 (28.3) 69 (63, 76) 16 (30) 137 (71.7) 52 (45, 58) 56(41) gong et al. (34) china, wuhan/ 189 nr 28 (14.8) 63.5 (54.5;72) 12 (42.9) 161 (85.2) 45(33, 62) 89 (55.3) guangdong liu et al. (35) china, chongqing 51 who guideline (30) 7 (13.7) 52 (44-60) 3 (42.9) 44 (86.3) 44 (33-49) 16 (36.4) qian et al. (36) china, zhejiang 91 respiratory distress/insufficiency 9 (9.9) 66 (54, 80) na 82 (90.1) 49 (35.5;56) na guan et al. (37) china, 30 provinces 1099 icu admission, m. ventilation, death 173 (15.7) 52 (40, 65) 73 (42.2) 926 (84.3) 45 (34, 57) 386 (41.8) wang et al. (38) china, wuhan 69 spo2 <90 14 (20.2) 70.5 (62, 77) 7 (50) 55 (79.8) 37 (32, 51) 30 (55) fan et al. (39) singapore 67 icu admission 9 (13.4) 54 (47-62) 3 (33.3) 58 (86.6) 41 (32-53) 27 (48.6) young et al. (26) singapore 18 required supplemental o2 6 (33.3) 56 (47-73) 4 (67) 12 (66.7) 37 (31-56) 4 (42) chen et al. (40) china, wuhan 21 spo2 <93% 11 (52.4) 63.9 (9.6) 1 (9.1) 10 (47.6) 51.4 (13.7) 3 (30) tang et al. (41) china, wuhan 449 death 134 (29.8) 68.7 (±11.4) 44 (32.83) 315 (70.2) 63.7 (±12.2) 137 (43.5) yang et al. (42) china, wuhan 52 death 32 (61.5) 64.6 (11.2) 11 (34) 20 (38.5) 51.9 (12.9) 6 (30) wei liu et al. (43) china, wuhan 78 admission to icu, death 11 (14.1) 66 (51, 70) 4 (36.4) 67 (85.9) 37 (32, 41) 35 (52.2) ruan et al. (44) china, wuhan 150 death 68 (45.3) 67 (15, 81) 19 (28) 82 (54.7) 50 (44, 81) 29 (35) wang et al. (25) china, fuyang/ 125 pao2 /fio2 ≤100 mmhg 25 (20) 49.4 (±13.64) 9 (36) 100 (80) 39.4 (±14.8) 45 (45) anhui n: number; icu: intensive care unit; who: world health organization; nr: not reported; m. ventilation: mechanical ventilation. 19 patients were collected from all of the included studies and are shown in table 2. as represented in figure 1, the asymmetry in the funnel plot reflects the presence of publication bias, which is also confirmed through the egger plot (figure 2) and egger test (p=0.04). the chi-square test for heterogeneity was significant (p=0.001), with the i2 value of 58%, implying medium dissimilarity in the included studies. then, a random effect model was applied to take into account the heterogeneity and the publication bias. the results revealed that the platelet pooled mean difference (%95 confidence interval) was -21.5 [(-31.57, -11.43), p<0.001]. as represented in figure 2, non-severe cases of covid-19 had a significantly higher number of platelets compared to patients with severe disease. although our data show that thrombocytopenic covid-19 patients experience a more severe disease than sars-cov-2-infected cases with normal platelet count, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. bashash et al. 4 figure 1: a) the funnel plot with pseudo 95% confidence limits for publication bias in the included studies. b) the egger plot for publication bias the included studies. several limitations such as low sample size and uneven description of disease outcome, along with incomplete information on sampling time might have adversely affected our analysis. 4. discussion one of the darkest periods in the history of human medicine is recorded in 2020. it is not the dreaded nuclear war, but an outbreak of an insidious member of β-coronaviruses that this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e75 figure 2: platelet mean difference count for patients with severe and non-severe covid-19. wages a full-scale war against human health, intimidating the peoples of nations and continents (15). considering the fact that sars-cov-2 infection has brought the national healthcare systems of nearly all countries __even those with highly developed medical facilities__ to their knees, battling with this lethal virus seems to be not easy but not impossible either. regardless of its innate designation (16), the influential role of the laboratory is far beyond the etiological identification of pathogens and it is now practically established that this branch of the medical science is effectively contributing to determining the prognosis of a wide range of human diseases, including covid-19 (17, 18). even though the results of a recent study to establish a prediction model for the prognosis of sars-cov-2 infection (19) introduced c reactive protein, lactic dehydrogenase, and lymphocyte count as the most valuable laboratory parameters reflecting covid19 severity, articles continuously introducing novel biomarkers with the ability to predict disease outcome are published daily. therefore, considering the results of several recent studies reporting the prognostic value of platelet in patients with covid-19, it might not be unrealistic to assume that a decreased number of platelets may potentially serve as a simple and readily available biomarker to predict disease severity. patients with severe diseases frequently have decreased numbers of platelets, and the emergence of thrombocytopenia is usual in such a situation mainly as a result of unrestricted consumption due to intravascular coagulopathy, often evolving towards disseminated intravascular coagulation (dic) (20). notably, the results of our recent meta-analysis revealed that the elevated level of d-dimers may predict the progression of covid-19 toward an unfavorable prognosis, further highlighting the fact that sars-cov-2-induced coagulopathy is responsible for disease severity (21). while the precise explanation for the occurrence of thrombocytopenia in patients with covid-19 is unknown, direct infection of bone marrow cells by the virus, platelet destruction by the immune system, and platelet aggregation in the lungs, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem d. bashash et al. 6 table 2: values of platelet count in severe and non-severe covid-19 patients platelet count non-severe severe huang et al. (24) 149 (131-263) 196 (165-263) cao et al. (28) 177 (143-220) 147 (120-179) zhang et al. (29) 175 (136-213) 169 (111-202) wan et al. (31) 170 (136-234) 147 (118-213) wang et al. (32) 165 (125-188) 142 (119-202) zhou et al. (33) 220 (168-271) 165.5 (107-229) gong et al. (34) 180 (147221) 167 (139.5-200) liu et al. (35) 192 (139-237) 150 (116-225) qian et al. (36) 198 (144-248) 152 (127-208) guan et al. (37) 172 (139-212) 137 (99-179) wang et al. (38) 172 (138-206) 167 (144-215) fan et al. (39) 201 (157-263) 217 (154-301) young et al. (26) 159 (128-213) 156 (116-217) chen et al. (40) 161 ±44.2 164 ±45.8 tang et al. (41) 231 ±99 178 ±92 yang et al. (42) 164 ±74 191 ±63 wei liu et al. (43) 173.20 ±55.37 143.90 ±64.81 ruan et al. (44) 222.1 ±78.0 173.6 ±67.7 wang et al. (25) 169.5 (142-212) 163.4 ±60.263 data are presented as mean ± standard deviation or mean (95% confidence interval). resulting in microthrombi were proposed as the plausible mechanisms underlying decreased platelet counts in those affected with the disease (20, 22). since platelets are released from fully mature megakaryocytes residing in the lung, structural change or decrease in the pulmonary capillary bed may also provoke unfortunate defragmentation of platelets (23). to provide a clear viewpoint demonstrating the prognostic value of platelet count in this novel infection, we performed a meta-analysis of pertinent literature representing information on the indicated parameter in patients with a clinically validated definition of severe disease. notably, the mean and median ages of severely ill patients were more than 50 years old in all the studies, except for huang et al. (24) and wang et al. (25) studies. besides, the percentage of men with severe disease was greater than women, except for the report by young et al. (26); further highlighting the fact that male sex and old age are amongst significant risk factors for progression of covid-19 towards an unfavorable outcome. the result of our meta-analysis of 19 studies, totaling 3383 covid19 patients with 744 (21.9%) severe cases, revealed that low platelet count is associated with increased risk of severe disease with the pooled mean difference of -21.5 (%95 ci: -31.57, -11.43), and thus proposed that thrombocytopenic covid19 patients will experience disease with a higher risk of adverse outcome. in agreement with thee findings, a recent study conducted on 383 patients, 49 (12.8%) of whom died, proposed platelet count as an independent risk factor associated with in-hospital mortality and reported that increment of per 50 × 109/l in platelets was associated with 40% decrease in mortality (hazard ratio: 0.60, 95%ci: 0.43, 0.84) (27). in conclusion, we believe that daily monitoring of the platelet count has a specific clinical significance in this infection and the appearance of thrombocytopenia may mirror the progression of covid-19 toward an unfavorable outcome. although the results of this study declared the prognostic significance of platelet count in sars-cov-2 infection, several limitations ranging from inadequate studies to fickle study design, either concerning different sampling times or underlying medical conditions, may have adversely affected our analysis. since in some papers, mean ± sd was only shown in graphs, it was not possible to include them. in addition, several articles did not mention either study population or clear statistical analysis. asymmetrical form of funnel plot also suggests that there is publication bias, showing overestimation in studies with lower sample size. finally, since covid19 is a recent hot topic and researchers are mostly motivated to publish their papers in local and regional journals as soon as possible, restricting to english-language search was another review-level limitation. 5. conclusion daily monitoring of platelet count has specific clinical significance in this infection, and the appearance of thrombocytopenia may mirror the progression of covid-19 towards an unfavorable outcome. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e75 6. declarations 6.1. acknowledgements the authors would like to thank shahid beheshti university of medical sciences for supporting this study. 6.2. authors contributions db, fh, ms and na: data collection and checklist scoring. db, fh and mf: data analysis and interpretation of the results. db: writing original draft. db, mr and ha: conceptualization, writing review & editing. 6.3. funding support none. 6.4. conflict of interest the authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of 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wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine. 2020. 43. liu w, tao z-w, lei w, ming-li y, kui l, ling z, et al. analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. chin med j. 2020. 44. ruan q, yang k, wang w, jiang l, song j. clinical predictors of mortality due to covid-19 based on an analysis of data of 150 patients from wuhan, china. intensive care med. 2020:1-3. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction method results discussion conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e72 rev i ew art i c l e the prevalence of underlying diseases and comorbidities in covid-19 patients; an updated systematic review and meta-analysis sorour khateri1, hedyeh mohammadi1, rozhin khateri2∗, yousef moradi3 † 1. school of medicine, kurdistan university of medical sciences, sanandaj, iran. 2. faculty of nursing and midwifery, kurdistan university of medical sciences, sanandaj, iran. 3. social determinants of health research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. received: july 2020; accepted: august 2020; published online: 12 september 2020 abstract: introduction: gaining knowledge about underlying diseases and associated comorbidities in patients with covid-19 can be beneficial in developing a proper understanding of the disease prognosis as well as comprehensive management, and treatment of the disease. the aim of this study was to determine the prevalence of underlying diseases and associated comorbidities in covid-19 patients using a systematic review and metaanalysis. methods: major biomedical electronic databases, including scopus, pubmed, web of science, cinahl and embase were searched for all relevant literature published in english from january to july 2020. crosssectional and retrospective studies reporting the prevalence of comorbid conditions such as acute cardiac injury, acute myocardial infarction, acute kidney injury, acute liver injury, shock, acute respiratory disease, and acute respiratory distress syndrome in patients with covid-19 were included in the study. after selecting eligible studies, two authors extracted data of each study, independently, and any inconsistency was resolved through discussion with the third reviewer until reaching a consensus. the risk of bias was assessed by two independent research experts using the newcastle-ottawa scale (nos). the variance in the meta-analyses on prevalence was stabilized by double arcsine transformations. results: the pooled prevalence of acute respiratory injury in patients with covid-19 was estimated as 34% (95% cl: 10 – 57%). also, the prevalence of acute kidney injury, acute liver injury, acute respiratory distress syndrome, and shock were estimated as 10% (95% cl: 6 14%), 19% (95% cl: 10 27%), 23 % (95% cl: 19 27%), and 12 % (95% cl: 5 – 19 %). conclusion: according to this meta-analysis, comorbidities such as hypertension, acute liver and kidney injury, acute respiratory distress syndrome, shock, diabetes, and coronary heart disease seem to be a predisposing factor for symptomatic and severe covid-19 infection. keywords: comorbidity; prognosis; covid-19; systematic review; meta-analysis cite this article as: khateri s, mohammadi h, khateri r, moradi y. the prevalence of underlying diseases and comorbidities in covid-19 patients; an updated systematic review and meta-analysis. arch acad emerg med. 2020; 8(1): e72. 1. introduction in late december 2019, a series of unexplained cases of pneumonia were reported in wuhan, china. the government and ∗corresponding author: rozhin khateri; faculty of nursing and midwifery, kurdistan university of medical sciences, sanandaj, iran. khateriroj@gmail.com † corresponding author: yousef moradi; social determinants of health research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. email: khateriroj@gmail.com, yousefmoradi211@yahoo.com, tel: 009183847065 health researchers in china took swift steps to control the spread of the epidemic and launched etiological studies. on january 12, 2020, the who declared the novel coronavirus (2019-ncov ) epidemic as a public health emergency of international concern (pheic). on february 11, 2020, who officially named the disease caused by 2019-ncov as covid19 (1, 2). the novel 2019 coronavirus (sars-cov-2) belongs to the beta-coronavirus group (3). the 2019-ncov is thought to be transmitted through droplets, close contact, aerosols, and possibly through fecal-oral transmission, and patients in the incubation period can transmit the virus to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 2 others (4, 5). the distribution of viral receptor can explain the pathogenic mechanisms, clinical manifestations, and transmission routes of the 2019-ncov. angiotensin-converting enzyme 2 (ace2) has been introduced as the receptor for the 2019-ncov, which is essential for its entry. expression of ace2 in various cells, such as pulmonary at2 cells, the upper esophagus, epithelial cells, and absorption enterocytes of the ileum and large intestine, may play a role in multi-tissue infection of 2019-ncov (6, 7). the disease usually causes viral pneumonia similar to influenza often about a week after the onset of the first symptoms, and causes shortness of breath, decreased oxygen saturation in the blood, and death in people with underlying disorders (8). renal disorders and septic shock have also been identified as other causes of death from covid-19 (9, 10). due to the novelty of the disease and the occurrence of most cases in china, the number of deaths or disabilities caused by it is still unknown. the rate of need for intensive care in hospitalized patients in china was reported to be between 23% and 32%, and the mortality rate was reported to be from 4.3% to 15% in the first articles published by chinese centers (3). with the spread of the disease to 114 countries, covid-19 outbreak was announced to be a pandemic on march 11, 2020 (2). in other countries of the world, as well as an increase in the number of diagnosed cases with less severe symptoms, led to changes in mortality rates and in the variables affecting death (11). finding the disease’s accurate mortality rate requires designing targeted cohort studies to more accurately record the number of those affected and patients who die and more consistently identify low-symptom patients (12). since many hospitalized patients, especially those who are eventually hospitalized in the icu or die, suffer from comorbidities such as diabetes, hypertension, chronic cardiovascular disease, etc., determining the frequency or prevalence of these underlying diseases and associated comorbidities can be beneficial in developing a proper understanding of the disease prognosis as well as comprehensive management, and treatment of the disease. to find a reliable answer, we performed a systematic review and meta-analysis, which estimated the pooled prevalence of underlying diseases and comorbidities in all patients. these findings may aid in patient management, mortality prevention, and development of policies regarding response to covid-19 and predicting its outcome. the aim of this study was to determine the prevalence of underlying diseases and associated comorbidities in covid-19 patients using a systematic review and meta-analysis. 2. methods we performed this systematic review using the metaanalyses of observational studies in epidemiology (moose)(13) and preferred reporting items for systematic reviews and meta-analyses (prisma)(14). 2.1. search terms and search strategy a comprehensive systematic search was implemented combining text-word and subject heading (mesh or equivalent) of the following online databases: pubmed (including medline), web of science, scopus, cinahl and embase; searching for articles published from january to july 2020. to search in the electronic databases, we applied all possible keywords related to "covid-19", "coronavirus", "acute cardiac injury", "acute myocardial infarction", "acute kidney injury", "acute liver injury", "shock", "acute respiratory disease" and "acute respiratory distress syndrome". the search strategies in embase and pubmed are shown in table 1. the primary search results were received and some of the articles were omitted based on their titles and abstracts. direct contact with authors was attempted in case there was incomplete information or any clarification was required. an identical search strategy was conducted in other databases. further, hand-searching of the key journals and the reference lists of the included papers was also performed. 2.2. selection and screening the articles were selected in two steps. first, two independent authors (skh and rkh) of this study reviewed the articles found, and evaluated them for meeting inclusion and exclusion criteria based on their title and abstract, and then abolished irrelevant studies. second, the full-text of the remaining articles from the previous stage was extracted and explored independently by each of the authors to determine the eligibility of the articles. finally, we selected 12 scientific articles about prevalence of comorbidities in patients with covid-19 (figure 1). prisma diagram was drawn to illustrate the study selection process. to identify any missing studies, we checked the reference list of each selected paper. 2.3. inclusion criteria in this study, full-text articles published as original research in scientific journals were selected in the first step. in addition, studies reporting the prevalence of comorbid conditions like acute cardiac injury, acute myocardial infarction, acute kidney injury, acute liver injury, shock, acute respiratory disease, and acute respiratory distress syndrome in patients with covid-19 were included in the study. in addition, cross-sectional and retrospective studies published in english, which assessed and reported the number of patients with covid-19 were included. 2.4. exclusion criteria reports, brief reports, books, textbooks, dissertations, reviews, letter to the editor, case reports, case studies, landscape articles, symposia, posters, brief communications, unthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e72 official interpretations, non-english articles, and articles unrelated to prevalence of comorbid conditions in patients with covid-19 were excluded. in addition, studies whose content was not related to the subject of research, or had either incorrect or vague information were excluded. 2.5. data extraction at this stage of the review, an initial data extraction form was prepared. the elements of information were extracted from each article in two parts: general items (first author, publication year, country, age, gender, and study population) and specific items (type of underlying disease, and comorbidity). then, two authors (skh and hm) separately reviewed and collected the data for each item. in addition, disagreement between the two authors, if any, was resolved through intervention of a third party. in the next step, the results were analyzed in a descriptive manner and the topics were grouped and meta-analyzed. these items are described in the results section of this article. 2.6. risk of bias qualitative evaluation of studies, based on the newcastleottawa quality assessment scale (nos) (15), was performed by two of the authors (ym and rkh). this scale is designed for qualitative evaluation of observational studies. nos examines each study for six items in three groups; selection, comparability, and exposure. points are given to each item and the maximum score is 9. finally, the articles were categorized as low, moderate, and high risk. the strengthening the reporting of observational studies in epidemiology (strobe) checklist was also completed for all articles (16, 17). 2.7. statistical analysis the variance in meta-analyses on prevalence was stabilized by double arcsine transformations. forest plots, x2 test (at a significance level of 10%) and i2 index were used to study the heterogeneity among the selected articles. a randomeffects model was applied for articles with high heterogeneity (i2>50%); for other cases, a fixed effects model was used. the year of publication and the age of patients were regarded to select a meta-regression considering the source of heterogeneity. statistical analyses were performed using stata 14.0 (stata corp, college station, tx, usa) and statistical significance was set at p < 0.05. 3. results 3.1. study characteristics 312 articles were initially retrieved by applying the search strategies in the online databases. among these articles, 53 duplicate publications were identified and removed. the remaining ones were screened based on their titles and abstracts. 12 articles were selected as the final papers to be analyzed (18-29) (figure 1). a total of 2393 patients with covid-19 (1250 male and 1089 female) were evaluated through 6 retrospectives, 4 cross-sectional, and 2 cohort studies. comorbidities assessed in these studies included coronary heart disease, diabetes, hypertension, chronic obstructive pulmonary disease (copd), acute cardiac injury, acute kidney injury, acute liver injury, acute respiratory distress syndrome and acute respiratory disease. the smallest and largest groups consisted of 41 and 788 patients, respectively. the studies were done in china. some other diseases such as dementia, cancers, mental disorders, hepatitis b virus, and psychological diseases had also been evaluated by some scientists, which were excluded due to their very low prevalence in our assay (table 2). 3.2. quantitative analysis the pooled prevalence of acute respiratory injury the lowest reported prevalence rate for acute respiratory injury in patients with covid-19 was 8% (95% cl: 3 13%) in the study by chen, n. et al. (21) and the highest acute respiratory injury prevalence rate was 67% (95% cl: 5580%), reported in the retrospective study by yang, x. et al.(29) in total, the pooled prevalence of acute respiratory injury has been estimated as 34% (95% cl: 10 57%; i2= 97.45%; q test = 156.93; p = 0.001) (figure 2). meta regression was used to explore the relationship of the independent variable (age) with the pooled prevalence of acute respiratory injury. the results of meta regression showed that the prevalence of acute respiratory injury has no relationship with age (coefficient: 0.017, p: 0.579, 95% ci: -0.043, 0.078). the pooled prevalence of acute respiratory injury in patients aged 60 years or less was 19% (95% cl: 1 37%; i2= 98.58%; q test = 140.77; p = 0.001) and in patients older than 60 years the prevalence was 43% (95% cl: 6 80%; i2= 80.37%; q test = 5.09; p = 0.02) (table 3). the pooled prevalence of acute kidney injury the pooled prevalence of acute kidney injury has been estimated as 10% (95% cl: 6 14%; i2= 48.39%; q test = 32.88; p = 0.09) (figure 2). the lowest and highest reported prevalence rates for acute kidney injury in patients with covid-19 were 2% (95% cl: 1 3%) and 29% (95% cl: 17 41%) in the studies by shi, s. et al. (18) and yang, x. et al.(29), respectively (figure 2). the results of meta regression showed that the prevalence of acute kidney injury has no relationship with age (coefficient: 0.016, p: 0.648, 95% ci: -0.005, 0.008). the pooled prevalence of acute kidney injury in patients aged 60 years or less was 9 % (95% cl: 3 15%; i2= 62.35%; q test = 5.77; p = 0.07) and in patients older than 60 years the prevalence was 11 % (95% cl: 5 16%; i2= 59.32%; this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 4 q test = 5.09; p = 0.24) (table 3). the pooled prevalence of acute liver injury the pooled prevalence of acute liver injury has been estimated as 19% (95% cl: 10 27%; i2= 43.57%; q test = 24.47; p = 0.21) (figure 3). the lowest and highest prevalence rates reported for acute kidney injury in patients with covid-19 were 3% (95% cl: 0 6%) and 45% (95% cl: 34 57%) in the studies by wang, d. et al. (26) and tang, x. et al. (25), respectively (figure 3). the results of meta regression showed that the prevalence of acute liver injury has no relationship with age (coefficient: 0.012, p: 0.110, 95% ci: -0.002, 0.028). the pooled prevalence of acute liver injury in patients aged 60 years or less was 15% (95% cl: 11 19%; i2= 0.0%; q test = 0.58; p = 0.31) and in patients older than 60 years the prevalence was 20% (95% cl: 7 34%; i2= 55.40%; q test = 4.99; p = 0.09) (table 3). the pooled prevalence of acute respiratory distress syndrome the lowest prevalence rate reported for acute respiratory distress syndrome in patients with covid-19 was 17% (95% cl: 10 25%) found in the study by chen, n. et al. (21) and the highest rate of acute respiratory distress syndrome prevalence was 31% (95% cl: 24 37%), reported in the retrospective study by zhou, f. et al. (27) in total, the pooled prevalence of acute respiratory distress syndrome has been estimated as 23% (95% cl: 19 27%; i2= 56.31%; q test = 9.16; p = 0.06) (figure 3). meta regression was used to explore the relationship of the independent variable (age) with the pooled prevalence of acute respiratory distress syndrome. the results of meta regression showed that the prevalence of acute respiratory distress syndrome has no relationship with age (coefficient: -0.003, p: 0.653, 95% ci: -0.019, 0.012). the pooled prevalence of acute respiratory distress syndrome in patients aged 60 years or less was 25% (95% cl: 19 31%; i2= 64.97 %; q test = 5.71; p = 0.08) and in patients older than 60 years the prevalence was 21% (95% cl: 15 27%; i2= 50.58%; q test = 2.02; p = 0.15) (table 2). the pooled prevalence of shock the pooled prevalence of shock has been estimated as 12% (95% cl: 5 – 19 %; i2= 87.25%; q test = 39.22; p = 0.001) (figure 3). the lowest and highest reported prevalence rates of shock in patients with covid-19 were 4% (95% cl: 0 8%) and 32% (95% cl: 21 42%) reported in the studies by chen, n. et al.(21) and tang, x. et al. (25), respectively (figure 3). the results of meta regression showed that the prevalence of shock has no relationship with age (coefficient: 0.010, p: 0.094, 95% ci: -0.001, 0.023). the pooled prevalence of shock in patients aged 60 years or less was 10% (95% cl: 4 17%; i2= 73.33%; q test = 14.67; p = 0.001) and in patients older than 60 years, it was 17% (95% cl: 10 44%; i2= 55.40%; q test = 22.53; p = 0.03) (table 3). the pooled prevalence of underlying diseases the pooled prevalence of admission to icu has been estimated as 23% (95% cl: 14 – 32 %; i2= 88.98%; q test = 36.29; p = 0.001) (figure 4). the results of meta regression showed that the prevalence of admission to icu has no relationship with age (coefficient: 0.008, p: 0.164, 95% ci: -0.003, 0.021). the pooled prevalence of admission to icu in patients aged 60 years or less was 23% (95% cl: 12 34%; i2= 91.12%; q test = 33.77; p = 0.001) (table 3). the pooled prevalence of diabetes in patients with covid-19 was 14% (95% cl: 11 18%; i2= 78.12%; q test = 45.71; p = 0.001) (figure 4). the pooled prevalence of diabetes in patients aged 60 years or less was 13 % (95% cl: 8 17%; i2= 77.47%; q test = 26.63; p = 0.001) and in patients older than 60 years, it was 18 % (95% cl: 12 24%; i2= 65.98%; q test = 8.82; p = 0.03) (table 3). the results of meta regression showed that the prevalence of admission to icu has no relationship with age (coefficient: 0.053, p: 0.174, 95% ci: -0.023, 0.130). the prevalence of hypertension in patients with covid-19 was 30% (95% cl: 23 37%; i2= 87.80%; q test = 65.58; p = 0.001) (figure 5). the results of meta regression showed that the prevalence of hypertension has a relationship with age (coefficient: 0.157, p: 0.029, 95% ci: 0.016, 0.029). also, the pooled prevalence rates of coronary heart disease and copd were 13% (95% cl: 8 18%; i2= 93.79%; q test = 160.90; p = 0.001) and 2% (95% cl: 1 3%; i2= 0.0%; q test = 5.06; p = 0.65), respectively (figure 5 and 6). the results of meta regression showed that the prevalence of coronary heart disease and copd has no relationship with age (coefficient: 0.106, p: 0.092, 95% ci: -0.017, 0.230) and (coefficient: -0.005, p: 0.537, 95% ci: -0.023, 0.012), respectively. also, the pooled prevalence of cancer in patients with covid-19 was 2% (95% cl: 1 3%; i2= 43.81%; q test = 10.68; p = 0.10) (figure 6). the prevalence of cancer has no relationship with age (coefficient: -0.006, p: 0.628, 95% ci: -0.031, 0.019). 4. discussion the results of this study showed that the pooled prevalence of acute respiratory injury in patients with covid-19 has been estimated as 34% (95% cl: 10 – 57%). also, the prevalence rates of acute kidney injury, acute liver injury, acute respiratory distress syndrome, and shock have been estimated as 10% (95% cl: 6 14%), 19% (95% cl: 10 27%), 23% (95% cl: 19 27%), and 12% (95% cl: 5 – 19 %), respectively. covid-19 is a respiratory infectious disease that causes the most damage to the lungs. people with the disease suffer from shortness of breath and severe cough. the virus infects and kills lung ciliated cells, which are responsible for clearing this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e72 viruses. when they are destroyed, the airways become filled with waste and fluids, thus activating the person’s immune system, which sends immune cells to the lungs to destroy the virus. in this process, however, the healthy tissues are also damaged and the lungs become inflamed. this inflammation affects the oxygen supply capacity of the lungs and can lead to death in acute cases. the us center for disease control and prevention reported that covid-19 was a threat to public health, and that older people with chronic medical conditions such as diabetes were at higher risk for severe illness and experiencing the side effects. studies have shown that the risk of developing severe side effects of covid-19 in people with diabetes is equal to normal people when the diabetes is controlled. on the other hand, the results of a study by leung, janice m. et al. showed that active smoking and copd increased the expression of ace-2 gene in the lower airways, which may to some extent justify the increased risk of covid-19 in these populations (30). the results of this study showed that the prevalence of hypertension in covid-19 patients (i2 index) was 91.45% with a confidence interval of 29.0 (95%: ci: 0.22 0.35). it is estimated that increased age has a positive effect on this rate. based on the results of recent studies, hypertension, cardiovascular disease, diabetes, kidney disease, smoking and copd were among the most important underlying diseases among covid-19 patients (31, 32). covid-19 is transmitted via the respiratory system. the disease mainly causes (severe) respiratory infections. all people are susceptible to the virus, but older people and those with underlying diseases are more likely to be infected and exposed to side effects. current findings have shown that mortality is very high in people with underlying diseases. in a study titled "evaluation of clinical symptoms in people with covid-19", zhang j-j et al. showed that cardiovascular disease is the most prevalent underlying disease among covid-19 patients according to existing medical evidence. it is worth noting that this pattern has also been found in middle east respiratory syndrome (mers) (31). based on the results, hypertension is one of the most common comorbid diseases, which has a direct correlation with age in patients with coronavirus. in the study of diabetes in patients with coronavirus, the results of this study showed that the prevalence of diabetes (i2 index) was 81.52% with a confidence interval of 13.0 (95%: ci: 0.10 0.17). it is estimated that increased age has a positive effect on this rate. xiaobo yang et al. concluded that 22% of patients with coronavirus have diabetes. in another study, among 1,099 patients with a definitive diagnosis of coronavirus, 16.2% had an active type of diabetes. research has shown that diabetes increases the risk of developing diseases such as influenza and pneumonia by reducing the power of the immune system, while controlling the rate of hyperglycemia reduces the risks. in fact, diabetes has been introdused as a risk factor for pandemic diseases such as influenza, covid-19 and severe respiratory failure. on the other hand, information on the prevalence of covid19 among diabetic patients is currently limited; 42.3% of covid-19-related death cases reported in wuhan, china had diabetes. another study on 150 patients with 68 deaths and 82 recovered patients in wuhan found that presence of underlying diseases was an important predictor of mortality. according to the results, diabetes is one of the most common underlying diseases, which is directly related to age in patients with coronavirus (33). in the study of heart failure in patients with coronavirus, the results showed that the prevalence of diabetes (i2 index) was 93.54% with a confidence interval of 0.11 (95%: ci: 0.08 0.14). it is estimated that increased age has a positive effect on this prevalence. studies show that coronavirus can increase the risk of heart failure and myocarditis, while increasing the patient’s resistance to treatment and increasing the risk of death from heart failure. reports in wuhan, china, have shown that heart failure is observed in 5 out of every 41 covid-19 patients with increased sensitivity to heart markers such as troponin. patients with palpitations and chest tightness with respiratory symptoms, such as fever and cough, were later diagnosed with covid-19. on the other hand, among the casualties of covid-19, 11.8% had high troponin levels without heart symptoms. therefore, it is seen in covid-19 patients due to systemic inflammatory response and immune system disorders during disease progression. a 12-year follow-up of 25 patients with various types of coronaviruses showed that 68% had hyperlipidemia and 44% had heart failure. according to the results of studies, heart failure is one of the most common associated diseases, which directly correlates with age in patients with coronavirus (34, 35). in the study of cancer in patients with coronavirus, it was shown that the prevalence of cancer (i2 index) was 52.54% with a confidence interval of 0.02. it is believed that increase in age has a positive effect on this prevalence. a study on 1590 covid-19 patients in wuhan, china, found that 18 patients had cancer, among whom only 4 underwent surgery or chemotherapy in the previous month, and 12 had recovered from cancer and had no clear indication of weakened immune system. therefore, it can be argued that patients with cancer will be prone to all kinds of infections due to receiving immunosuppressive drugs, so these patients are also more prone to coronavirus and have weaker diagnostic markers. as a result, chemotherapy can be delayed to reduce the mortality rate of these people during the coronavirus outbreak; also, stronger personal protection regulations, and closely monitoring the treatment of these people, especially the older patients, may help reduce their risk of infection. according to the results, cancer is one of the most common underlying diseases, which is directly related to age this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 6 in patients with coronavirus (36, 37). 5. limitation one of the limitations of our study is the high heterogeneity in some categories. also, in the results of included studies, potential confounder factors were not reported. so, subgroup analysis was done based on age, alone. in addition, the screening of articles found via the initial search, data extraction, and quality assessment of included articles may have been influenced by personal judgments. 6. conclusion in summary, the results of the present study showed that in patients with sars-cov-2 infection, hypertension, cardiovascular disease, smoking, and diabetes were the most common underlying disorders. therefore, due to the long and asymptomatic incubation period, it is often recommended that people with chronic diseases follow health advice more closely and avoid contact with other people. also, comorbid conditions like hypertension, acute liver injury, acute kidney injury, acute respiratory distress syndrome, shock, diabetes, and coronary heart disease seem to be a predisposing factor for symptomatic and severe covid-19 infection. 7. declarations 7.1. acknowledgements not applicable. 7.2. ethical approval and consent to participate not applicable. 7.3. consent for publication not applicable. 7.4. availability of data and material input data for the analyses are available by the corresponding author on request. 7.5. competing interests the authors declare that they have no competing interests. 7.6. funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 7.7. authors’ contributions skh, and ym conceptualized the idea for this review, formulated the review question, and objectives, assisted with the development of the final search strategy, contributed to the data analysis/ interpretation, and writing the manuscript. rkh, hm, skh and ym contributed to the conceptualization of the final review question, formulation of the review objectives, data analysis/interpretation, and writing the manuscript. all authors equally contributed to the formulation of the review question/objectives, development of the search strategy, conducting the searches, data extraction, data analysis/interpretation, and writing the manuscript. all authors read and approved the final manuscript. 7.8. conflict of interest the authors declare that they have no conflict of interests. references 1. gorbalenya ae. severe acute respiratory syndromerelated coronavirus–the species and its viruses, a statement of the coronavirus study group. biorxiv. 2020. 2. ung col. community pharmacist in public health emergencies: quick to action against the coronavirus 2019ncov outbreak. research in social and administrative pharmacy. 2020. 3. chen y, liu q, guo d. emerging coronaviruses: genome structure, replication, and pathogenesis. journal of medical virology. 2020;92(4):418-23. 4. wu f, zhao s, yu b, chen y-m, wang w, song z-g, et al. a new coronavirus associated with human respiratory disease in china. nature. 2020;579(7798):265-9. 5. zhang h, penninger jm, li y, zhong n, slutsky as. angiotensin-converting enzyme 2 (ace2) as a sars-cov2 receptor: molecular mechanisms and potential therapeutic target. intensive care medicine. 2020:1-5. 6. emery sl, 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distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e72 table 1: medline search strategy databases complex and simple search syntax embase (’covid 19’/exp or ’coronavirus disease 2019’/exp) and (’acute heart infarction’/exp or ’acute cardiac infarction’ or ’acute heart infarction’ or ’acute myocardial infarction’ or ’heart infarction, acute’ or ’acute kidney failure’/exp or ’acute kidney failure’ or ’acute kidney injury’ or ’acute kidney insufficiency’ or ’acute renal failure’ or ’acute renal insufficiency’ or ’kidney acute failure’ or ’kidney failure, acute’ or ’kidney insufficiency, acute’ or ’renal insufficiency, acute’ or ’liver injury’/exp or ’acute liver injury’ or ’blunt liver trauma’ or ’hepatic damage’ or ’hepatic injury’ or ’hepatic lesion’ or ’hepatic trauma’ or ’injury, liver’ or ’liver damage’ or ’liver injury’ or ’liver lesion’ or ’liver parenchymal injury’ or ’liver trauma’ or ’liver wound’ or ’trauma, hepatic’ or ’trauma, liver’ or ’wound, liver’ or ’shock’/exp or ’cardiovascular collapse’ or ’circulation shock’ or ’circulatory collapse’ or ’circulatory shock’ or ’incremental shock’ or ’nonseptic shock’ or ’shock’ or ’shock index’ or ’shock intensity’ or ’shock syndrome’ or ’shock, surgical’ or ’surgical shock’ or ’acute respiratory tract disease’/exp or ’acute respiratory disease’ or ’acute respiratory tract disease’ or ’respiratory disease, acute’ or ’adult respiratory distress syndrome’/exp or ’ards’ or ’acute respiratory distress syndrome’ or ’adult respiratory distress’ or ’adult respiratory distress syndrome’ or ’lung shock’ or ’posttraumatic lung failure’ or ’posttraumatic pulmonary insufficiency’ or ’respiratory distress syndrome, acute’ or ’respiratory distress syndrome, adult’ or ’respiratory distress, adult’ or ’shock lung’) pubmed (((((acute[all fields] and ("heart"[mesh terms] or "heart"[all fields] or "cardiac"[all fields]) and ("wounds and injuries"[mesh terms] or ("wounds"[all fields] and "injuries"[all fields]) or "wounds and injuries"[all fields] or "injury"[all fields])) or ("acute kidney injury"[mesh terms] or ("acute"[all fields] and "kidney"[all fields] and "injury"[all fields]) or "acute kidney injury"[all fields])) or (acute[all fields] and respiratory[all fields] and ("wounds and injuries"[mesh terms] or ("wounds"[all fields] and "injuries"[all fields]) or "wounds and injuries"[all fields] or "injury"[all fields]))) or (acute[all fields] and ("myocardial infarction"[mesh terms] or ("myocardial"[all fields] and "infarction"[all fields]) or "myocardial infarction"[all fields]))) or ("respiratory distress syndrome, adult"[mesh terms] or ("respiratory"[all fields] and "distress"[all fields] and "syndrome"[all fields] and "adult"[all fields]) or "adult respiratory distress syndrome"[all fields] or ("acute"[all fields] and "respiratory"[all fields] and "distress"[all fields] and "syndrome"[all fields]) or "acute respiratory distress syndrome"[all fields])) and (("covid-19"[all fields] or "covid-2019"[all fields] or "severe acute respiratory syndrome coronavirus 2"[supplementary concept] or "severe acute respiratory syndrome coronavirus 2"[all fields] or "2019-ncov"[all fields] or "sars-cov2"[all fields] or "2019ncov"[all fields] or (("wuhan"[all fields] and ("coronavirus"[mesh terms] or "coronavirus"[all fields])) and (2019/12[pdat] or 2020[pdat]))) or (("coronavirus"[mesh terms] or "coronavirus"[all fields]) and 2019[all fields])) this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 10 table 2: patient characteristics, underlying diseases, and comorbid conditions in patients with covid-19 authors (years) (country) study population (type of studies) sample size (male , female) age (year) chronic medical illness comorbid conditions huang, chaolin. et al. (2020) (28) china patients with 2019-ncov pneumonia(cross sectional) 41 (30 m, 11 f) 49 icu care (5/13: 38%) no icu care (1/28: 4 %) icu admitted (13/41: 31.7%) diabetes (8/41: 20 %) hypertension (6/41: 15 %) cardiovascular disease (6/41: 15%) copd (1/41: 2%) cancer (1/41: 1%) acute respiratory distress syndrome (12/41: 29%) rnaaemia (6/41: 15%) acute cardiac injury (5/41: 12%) acute kidney injury (3/41: 7%) shock (3/41: 7%) secondary infection (4 /41: 10 %) shi, s. et al. (2020) (18) china patients with 2019-ncov (cohort) 416 (205 m, 211 f) 64 (21 – 95) with cardiac injury (42/82: 51.2%) without cardiac injury (15/334: 51.2%) hypertension (127/416:30.5%) diabetes (60/416: 14.4%) coronary heart disease (4/416: 10.6%) cancer (9/416: 2.2%) copd (12/416: 2.9%) hbv (4 / 416: 1%) acute cardiac injury (82/416: 19.7%) ards (97/416: 23.3%) acute kidney injury (8/416: 1.9%) anemia (13/416: 3.1%) coagulation disorder (12/416: 2.9%) guo, t. et al. (2020) (19) china patients with 2019-ncov (cohort) 187 (91 m, 96 f) 58 elevated tnt level (31/52: 4.5 %) normal tnt level (12/135: 8.9 %) hypertension (61/187:32.6%) diabetes (28/187: 15%) coronary heart disease (21/187: 11.2%) cancer (13/187: 7%) copd (4/187: 2.1%) ards (46/187: 24.6%) acute kidney injury (18/187: 14.6%) acute liver injury (19/187: 15.4%) coagulation disorder (42/187: 34.1%) cai, q. et al. (2020) (20) china patients with 2019-ncov (cross sectional) 298 (145 m, 153 f) 47.5 length of hospital stay (20.5 [15-26] days) need for icu (30/298: 10.1%) cardiovascular disease (25/298: 8.39%) hypertension (47/298: 15.8%) diabetes (18/298: 6.04%) cancer (4/298: 1.3%) acute liver injury (44/298: 14.8%) acute kidney injury (17/298: 5.7%) acute cardiac injury (20/298: 6.7%) chen, n. et al. (2020) (21) china patients with 2019-ncov (cross sectional) 99 (67 m, 32 f) 20 90 cardiovascular and cerebrovascular diseases (40/99: 40 %) diabetes (12/99: 12%) respiratory system disease (1/99: 1%) cancer (1/99: 1 %) icu admitted (23/99: 23%) ards (17/99: 17%) acute respiratory injury (8/99: 8 %) shock (4/99: 4%) he, x. w. et al. (2020) (22) china patients with 2019-ncov (cross sectional) 54 (-) 68 (59.8 -74.3) hypertension (24/54: 44.4%) diabetes (13/54: 24.1%) coronary heart disease (8/54: 14.8%) copd (2/54: 3.7%) acute cardiac injury (24/54 :44.4%) lian, j. et al. (2020) (23) china patients with 2019-ncov (retrospective) 788 (407 m, 381 f) all age admitted icu (27/788: 3.42%) hypertension (126/788: 16%) coronary heart disease (11/788: 1.4%) diabetes (57/788: 7.23 %) liver disease (31/788: 3.93%) copd (3/788: 0.38%) cancer (6/788: 0.76%) acute respiratory distress (58/788: 7.36%) shock (2/788: 0.25%) liver function abnormality (82/788: 10.4%) acute kidney injury (13/788: 1.64%) liu, k. et al. (2020) (24) china patients with 2019-ncov (retrospective) 56 (31 m, 25 f) 47-68 hypertension (15/56: 26.78%) coronary heart disease (2/56: 3.57%) diabetes (4/56: 7.14 %) liver disease (1/56: 1.78%) acute respiratory distress syndrome (6/56: 10.71%) acute heart injury (7/56: 12.5%) acute liver and kidney injury (10/56: 17.85%) shock (3/56: 5.35%) tang, x. et al. (2020) (25) china patients with 2019-ncov (retrospective) 73 (45 m, 28 f) 67 hypertension (38/73: 52.1%) coronary heart disease (23/73: 31.5%) diabetes (20/73: 27.4%) kidney disease (3/73: 4.1%) leukocytopenia (60/73: 82.2%) shock (23/73: 31.5%) acute kidney injury (13/73: 17.8%) liver dysfunction (33/73: 54.%) wang, d. et al. (2020) (26) china patients with 2019-ncov (retrospective) 138 (75 m, 63 f) 56 icu (36/138: 26.08) hypertension (43/138: 31.2%) cardiovascular disease (20/138: 14.5%) diabetes (14/138: 10.1%) cancer (10/138: 7.2 %) copd (4/138: 2.9%) hiv (2 /138: 1.4%) shock (12/138: 8.7 %) acute cardiac injury (10/138: 7.2%) arrhythmia (23/138: 16.7%) ards (27/138: 19.6%) aki (5/138: 3.6%) kidney disease (4/138: 2.9%) liver disease (4/138: 2.9%) yang, x. et al. (2020) (28) china patients with 2019-ncov (retrospective) 52 (35 m, 17 f) 59.7 cardiovascular disease (5/52: 10%) diabetes (9/52: 17%) cancer (2/52: 4 %) copd (4/52: 8%) dementia (1/52: 2%) acute respiratory distress (35/52: 67%) acute kidney injury (15/52: 29%) liver dysfunction (15/52: 29%) acute cardiac injury (12/52: 23%) zhou, f. et al (2020) (27) china patients with 2019-ncov (retrospective) 191 (119 m, 72 f) 56 hypertension (26/54: 48%) cardiovascular disease (13/54: 24%) diabetes (17/54: 31%) copd (4/54: 7%) chronic kidney disease (2/54: 2%) icu admission (39/54: 72%) ards (50/54: 93%) shock (38/54: 70%) heart failure (28/54: 52%) acute kidney injury (27/54: 50%) acute respiratory distress (53/54: 98%) icu: intensive care unit; copd: chronic obstructive pulmonary disease; hbv: hepatitis b virus; ards: acute respiratory distress syndrome; tnt: troponin t; hiv: human immunodeficiency virus; aki: acute kidney injury. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e72 table 3: summary of prevalence estimates [95% confidence intervals (cis)] for underlying diseases and comorbid conditions in patients with covid-19 based on their age group according to the included studies subgroup study (n) pooled prevalence between studies between subgroups i2 (%) p* q q p* acute respiratory injury > 60 years 3 43 % (6 – 80 %) 80.37 0.02 5.09 ≤ 60 years 2 19 % (1– 37 %) 98.58 0.00 140.77 1.26 0.26 acute kidney injury > 60 years 6 11 % (5 – 16 %) 59.32 0.24 5.09 ≤ 60 years 3 9 % (3– 15 %) 62.35 0.07 5.77 0.17 0.68 acute liver injury > 60 years 4 20 % (7 – 34 %) 55.40 0.09 4.99 ≤ 60 years 2 15 % (11– 19 %) 0.0 0.58 0.31 0.55 0.46 acute respiratory distress syndrome > 60 years 2 21 % (15 – 27 %) 50.58 0.15 2.02 ≤ 60 years 3 25 % (19– 31 %) 64.97 0.08 5.71 0.82 0.36 shock > 60 years 2 17 % (10 – 44 %) 69.55 0.03 22.53 ≤ 60 years 4 10 % (4– 17 %) 73.33 0.001 14.67 0.24 0.63 admission to icu > 60 years 1 23 % (15 – 32 %) ≤ 60 years 4 23 % (12– 34 %) 91.12 0.001 33.77 0.01 0.94 diabetes > 60 years 4 18 % (12 – 24 %) 65.98 0.03 8.82 ≤ 60 years 7 13 % (8– 17 %) 77.47 0.001 26.63 1.84 0.18 copd > 60 years 3 2 % (1 – 4 %) 17.98 0.30 2.44 ≤ 60 years 5 3 % (1– 4 %) 0.0 0.691 2.24 0.35 0.56 cancer > 60 years 2 2 % (1 – 4 %) 0.0 0.35 0.88 ≤ 60 years 5 3 % (1– 3 %) 59.14 0.04 9.79 0.37 0.54 chd > 60 years 4 22 % (1 – 42 %) 97.04 0.001 101.38 ≤ 60 years 7 9 % (7– 12 %) 43.48 0.10 10.62 1.37 0.24 * heterogeneity. icu: intensive care unit; copd: chronic obstructive pulmonary disease; chd: coronary heart disease. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 12 figure 1: the diagram of study selection. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 13 archives of academic emergency medicine. 2020; 8(1): e72 figure 2: the pooled prevalence of acute respiratory and kidney injury in patients with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 14 figure 3: the pooled prevalence of acute liver injury, respiratory distress syndrome, and shock in patients with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 15 archives of academic emergency medicine. 2020; 8(1): e72 figure 4: the pooled prevalence of admission to icu and diabetes in patients with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. khateri et al. 16 figure 5: the pooled prevalence of hypertension and coronary heart disease in patients with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 17 archives of academic emergency medicine. 2020; 8(1): e72 figure 6: the pooled prevalence of chronic obstructive pulmonary disease (copd) and cancer in patients with covid-19. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declarations references emergency. 2018; 6 (1): e40 or i g i n a l re s e a rc h new molecular aspects of cardiac arrest; promoting cardiopulmonary resuscitation approaches mona zamanian-azodi1, mostafa rezaei tavirani1∗, mohammad rostami-nejad2, fatemeh tajik-rostami3 1. proteomics research center, faculty of paramedical sciences, shahid beheshti university of medical sciences, tehran, iran. 2. gastroenterology and liver diseases research center, research institute for gastroenterology and liver diseases, shahid beheshti university of medical sciences, tehran, iran. 3. faculty of medicine, iran university of medical sciences, tehran, iran. received: may 2018; accepted: july 2018; published online: 2 july 2018 abstract: introduction: cardiopulmonary resuscitation (cpr) is a method to improve survival of patients with cardiac arrest. this study aimed to identify the key genes affected five minutes after cardiac arrest, hoping to elevate the efficacy of cpr. methods: in this bioinformatics study differentially expressed genes of six pigs were downloaded from geo and screened. the significant and characterized genes were analyzed via calculating fold change and protein-protein interaction (ppi) networks. the crucial nodes were determined based on centrality parameters and their related biological processes were investigated via cluego. results: 17 significant up-regulated (logfc ≥ 2) and 22 down-regulated (logfc < -0.5) genes were detected. transthyretin (ttr logfc = 4.59) and gonadotropin-releasing hormone receptor (gnrhr logfc = 3.84) had higher logfc among up-regulated and down-regulated genes, respectively. the critical genes including four up-regulated and five down-regulated genes were detected from network analysis. gnrhr and prolactin precursor (prl) were among the most important down res 5 minutes after cardiac arrest and beta-2 adrenergic receptor and cadherin-1 were among the most important up regulated gens. conclusion: the introduced potential biomarkers could reveal a new molecular aspect for cpr performance and pituitary gland protection was highlighted in this respect. keywords: cardiac arrest; cardiopulmonary resuscitation; protein interaction maps; gene ontology, biomarkers © copyright (2018) shahid beheshti university of medical sciences cite this article as: zamanian-azodi m, rezaei tavirani m, rostami-nejad m, tajik-rostami f. new molecular aspects of cardiac arrest; promoting cardiopulmonary resuscitation approaches. 2018; 6(1): e40. 1. introduction c ardiopulmonary resuscitation (cpr) is established and developed to increase perfusion in cardiac arrest patients and improve their survival (1). although resuscitation science has progressed remarkably, poor survival of cardiac arrest patients is a still a problem in medicine (2). there are evidence that the majority of survivors are neurologically damaged in the short term, which can lead to long term disorders (3). post cardiac arrest syndrome as well as high rate of in hospital mortality after cpr are reported and discussed (4). ∗corresponding author: mostafa rezaei tavirani; shahid beheshti university of medical sciences, velenjak, shahid aarabi avenue, tehran, iran. email: tavirany@yahoo.com tel: +982122439787 attempts have been made to understand the molecular and cellular aspects of cpr, which can help to improve the quality of life in patients who survive (5). in addition, treatment with chemical reagents could improve the outcome of cpr performance. for instance, it has been reported that nitric oxide inhalation improves cpr outcome in animal model (6). recently, high throughput molecular investigations including proteomics and genomics have provided large amounts of data and have attracted the attention of researchers in various fields of medicine and pharmacology. martijn and wiklund published valuable microarray data about cpr in pigs, which is a useful molecular source about cpr (7). there are various methods that are useful for decreasing the volume of data and highlighting the remarkable components (8). protein-protein interaction (ppi) networks analysis is an attractive method to screen disease-related genes (9, 10). in this approach, the genes or proteins are organized in an interactome unit and the critical elements are identified (11, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. zamanian-azodi et al. 2 12). in this study, the aim was to identify crucial cpr related genes among the large number of genes introduced by martijn and wiklud (7) using ppi network analysis. the findings will promote molecular aspects of cpr, which is important to elevate the efficacy of cpr methods. 2. methods 2.1. study design and setting this bioinformatics study was conducted via evaluating gene expression changes in the animal model of cardiac arrest 5 minutes after its incidence, for better programing of treatment approaches and cpr performance. the selected groups were from one genomic study conducted by martijn and wiklud (7). in the mentioned original study, three groups are available with different time courses and treatments. the protocol of the present study was approved by ethics committee of shahid beheshti university of medical sciences. 2.2. participants data of differentially expressed genes of six pigs’ brain samples (sus scrofa) were downloaded from gene expression omnibus (geo). the animals were cardiac arrested as described in the report of miclescu, basu, and wiklund (13). 3 animals in control group (0 minute after cardiac arrest) and 3 in case group (5 minutes after cardiac arrest) were considered for analysis. 2.3. procedure after downloading and screening 250 differentially expressed genes from geo, the next step was to construct a network of interactions. the hub-nodes were identified via mean ± 2 standard deviation cut off on degree values and the top 5% of the nodes based on betweenness centrality were considered as bottleneck-genes. common hub and bottleneck genes were introduced as hub-bottleneck nodes (the crucial genes). detail of gene expression assay is explained in the report of martijn and wiklud (7). box plot finding indicates that the mid points of data are in the same range; therefore, samples are comparable in terms of gene expression. 2.4. statistical analysis the differentially expressed genes with a fold change (fc) above 2 (for up-regulated genes) and below -0.5 (for downregulation) were selected for analysis. considering p ≤ 0.01 and elimination of uncharacterized genes, the candidate genes were determined. the ppi network was constructed using cytoscape software version 3.6.0 via its string plugin (14). cluego was used for gene ontology analysis of the introduced key genes. 3. results: 3.1. fold change analysis logfc of the 59 differentially expressed genes is calculated and shown in figure 1 (37 up-regulated and 22 downregulated). based on fold change analysis, 17 significant up-regulated (logfc ≥ 2) and 22 significant down-regulated (logfc < -0.5) genes were detected. transthyretin (ttr logfc = 4.59) and gonadotropin-releasing hormone receptor (gnrhr logfc = 3.84) had higher logfc among up-regulated and down-regulated genes, respectively. 3.2. ppi network analysis the ppi network contained 29 isolated nodes and a main connected component including 72 linked genes with 634 edges (figure 2). the critical genes including four upregulated and five down-regulated genes were detected via network analysis and listed in table 1. gnrhr and prolactin precursor (prl) were among the most important downregulated genes 5 minutes after cardiac arrest and beta-2 adrenergic receptor and cadherin-1 were among the most important up-regulated genes based on this analysis. gnrhr is highlighted as the top central gene following ppi network analysis; however, ttr was not remarkable in this analysis. 4. discussion there are many investigations about events occurring after a cardiac arrest and intervention approaches in this regard. many factors could play a role in the quality of life after cpr. one of the key factors is timing (7). to improve the medical care in this state, understanding the pathophysiology of ca is critical. investigating molecular mechanisms could assist in reaching this goal. molecular changes are the main corresponding features of any organism’s profile (11, 12). in this respect, one way is to analyze gene expression profile of patients with cardiac arrest to set new diagnosis and treatment strategies. in our bioinformatics study, animal model of cardiac arrest was selected for further evaluations to provide a molecular view of cardiac arrest for promoting cpr procedure. comparison of samples depicted that there are genes with significant expression values, in which up-regulation is dominant. these vast expression changes within 5 minutes post cardiac arrest express that there are complex molecular changes in this state. further analysis evaluates the role and contribution of these genes to pathophysiology 5 minutes after cardiac arrest, which can lead to organ injury. ttr and gnrhr were the most up-regulated and down-regulated genes in the study, respectively. plasma ttr with high concentration level is responsible for transportation of thyroxine and retinol, but within the mamthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e40 figure 1: log fold change (fc) of the 59 differentially expressed genes. blue color: up-regulated genes; red color: down-regulated genes. table 1: list of central genes (hub-bottleneck nodes) of the main connected component (only including query genes) genes description degree centrality* gnrhr gonadotropin-releasing hormone receptor 22 0.05 prl prolactin precursor 21 1.00 adrb2 beta-2 adrenergic receptor 20 0.77 lhb lutropin subunit beta 18 0.04 amcf-ii alveolar macrophage chemotactic factor 2 17 0.19 cdh1 cadherin-1 14 0.02 mmp-13 matrix metalloproteinase-13 13 o.57 insr insulin receptor 12 0.00 igf2 insulin-like growth factor ii 11 0.13 *normalized betweenness centrality; red color: up-regulation; green color: down-regulation. malian central nervous system it may play another role (16). it seems that, the vast expression change of ttr may be corthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. zamanian-azodi et al. 4 figure 2: the main connected component of protein-protein interaction network of the cardiac arrested pigs. the bigger size and the blue color nodes refer to higher degree value. the uncharacterized nodes are shown in the bottom right corner. related to the possible decrement of thyroxin hormone, the concentration of which is controlled by the pituitary gland. gnrhr and its gnrh are important endocrine elements in regulation of reproduction (17). nine crucial genes are recognized as vital elements of cardiac arrest ppi network, which are divided in the two sub-groups of up-regulated and downregulated genes (see table 1). it seems that biological interactions between the nine highlighted genes may play significant roles in cardiac arrest and could be important for cpr. it is reasonable to consider adrb2, cdh1, igf2, insr, prl, lhb, and gnrhr as candidate biomarker panel of cardiac arrest after 5 minutes. it is reported that adrb2 affects the lungs to change fluid clearance (18). various types of activity such as role in different cancers, axon growth, and brain metabolism are reported for cdh1 gene (19-22). insulin-like growth factor ii is an embryonic growth factor and its expression is reported in most tissues. the relationship between igf2 and a number of cancers and cardiomyopathy has been investigated (23, 24). a glucose-insulin-potassium infusion is considered for cardiac arrest; however, it does not have an effect on reduction of mortality (25). it seems that insulin (or its receptor) is linked to cardiac arrest (26). prl and gnrh are the two important hormones of pituitary gland and their well-known function is to play a critical role in lactation and fertility (27, 28). subunit beta of gonadal lutropin is responsible for receptor binding of the hormone (29). as mentioned, the crucial genes are directly related to pituitary gland. thus, this finding implies that the protection of this vital gland could be critical during cpr. hence, simultaneous treatment intervention is suggested for cpr promotion. on the other hand, the biological processes that are related to the pituitary gland may be damaged in the survivors. it is possible that a young survivor loses fertility or experiences some related disorders. the other significant point is the possible role of these critical genes in increasing the percentage of successful administration of cpr. complementary research on survivors is required to support the findings of this study. 5. conclusion the finding indicates that pituitary gland is a sensitive part during cardiac arrest and its protection should be considered in cpr guidelines. 6. appendix 6.1. acknowledgements this project is supported by shahid beheshti university of medical sciences. 6.2. author contribution all authors meet the standard criteria of authorship based on the recommendations of the international committee of medical journal editors. 6.3. funding this project is supported by shahid beheshti university of medical sciences. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e40 6.4. conflict of interest the authors declare that they have no conflict of interest. references 1. cave dm, gazmuri rj, otto cw, nadkarni vm, cheng a, brooks sc, et al. part 7: cpr techniques and devices. circulation. 2010;122(18 suppl 3):s720-s8. 2. yeung j, meeks r, edelson d, gao f, soar j, 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www.jemerg.com m. zamanian-azodi et al. 6 vates epicardial igf2. development. 2011;138(1):139-48. 25. mehta sr, yusuf s, diaz r, zhu j, pais p, xavier d, et al. effect of glucose-insulin-potassium infusion on mortality in patients with acute st-segment elevation myocardial infarction: the create-ecla randomized controlled trial. jama. 2005;293(4):437-46. 26. stellpflug sj, harris cr, engebretsen km, cole jb, holger js. intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. clinical toxicology. 2010;48(3):227-9. 27. la rosa s, celato n, uccella s, capella c. detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry. virchows archiv. 2000;437(3):2649. 28. freeman me, kanyicska b, lerant a, nagy g. prolactin: structure, function, and regulation of secretion. physiological reviews. 2000;80(4):1523-631. 29. cosowsky l, rao sv, macdonald gj, papkoff h, campbell rk, moyle wr. the groove between the α-and βsubunits of hormones with lutropin (lh) activity appears to contact the lh receptor, and its conformation is changed during hormone binding. journal of biological chemistry. 1995;270(34):20011-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references emergency. 2018; 6 (1): e42 or i g i n a l re s e a rc h glasgow coma scale and four score in predicting the mortality of trauma patients; a diagnostic accuracy study parisa ghelichkhani1, maryam esmaeili2∗, mostafa hosseini3, khatereh seylani4 1. department of intensive care nursing, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 2. nursing and midwifery care research center, school of nursing and midwifery, tehran university of medical sciences, tehran, iran. 3. department of epidemiology and biostatistics, school of public health, tehran university of medical sciences, tehran, iran. 4. school of nursing and midwifery, tehran university of medical sciences, tehran, iran. received: april 2018; accepted: june 2018; published online: 14 july 2018 abstract: introduction: many scoring models have been proposed for evaluating level of consciousness in trauma patients. the aim of this study is to compare glasgow coma scale (gcs) and full outline of unresponsiveness (four) score in predicting the mortality of trauma patients. methods: in this diagnostic accuracy study trauma patients hospitalized in intensive care unit (icu) of 2 educational hospitals were evaluated. gcs and four score of each patient were simultaneously calculated on admission as well as 6, 12 and 24 hours after that. the predictive values of the two scores and their area under the receiver operating characteristics (roc) curve were compared. results: 90 patients were included in the present study (mean age 39.4±17.3; 74.4% male). comparing the area under the roc curve of gcs and four score showed that these values were not different at any of the evaluated times: on admission (p=0.68), and 6 hours (p=0.13), 12 hours (p=0.18), and 24 hours (p=0.20) after that. conclusion: the results of our study showed that, gcs and four score have the same value in predicting the mortality of trauma patients. both tools had high predictive power in predicting the outcome at the time of discharge. keywords: glasgow coma scale; wounds and injuries; trauma severity indices; outcome assessment (health care); critical care; intensive care units © copyright (2018) shahid beheshti university of medical sciences cite this article as: ghelichkhani p, esmaeili m, hosseini m, seylani kh. glasgow coma scale and four score in predicting the mortality of trauma patients; a diagnostic accuracy study. emergency. 2018; 6(1): e42. 1. introduction i n severe injuries, especially traumatic brain injuries, a considerable portion of the patients are hospitalized in intensive care unit (icu). in recent years, the prevalence of injuries has significantly increased in developing countries. based on the latest reports of world health organization, injury is the tenth cause of mortality in the world and third cause of death in iran. this high prevalence leads to increased treatment costs, loss of society’s work force, greater burden of diseases and increase in the workload of treatment staff, especially nurses (1-3). by using appropriate tools for ∗corresponding author: maryam esmaeili; school of nursing and midwifery, tehran university of medical sciences, nosrat st., tohid sq.,tehran,iran. tel: +982166937120 fax: +982166904252 email: mesmaeilie77@gmail.com, esmaeili_m@tums.ac.ir measuring the level of consciousness to evaluate the severity of the injury in head trauma patients, nurses will be able to prepare for taking critical measures for the injury in the shortest time and in the best possible way and reduce the disability and mortality of trauma patients (4-12). many scoring models have been proposed to evaluate level of consciousness in patients who are affected with traumatic brain injuries, the most famous of which is glasgow coma scale. this scale has some limitations such as its low efficiency in intubated patients, its poor use in cases of language differences, and not being able to evaluate the reflexes of brainstem (13, 14). in intubated patients, the verbal part is practically non-measurable and therefore, it is possible that the reported level of consciousness in these patients is lower than its real level (15). full outline of unresponsiveness (four) score is another scale for evaluating level of consciousness, the accuracy and precision of which in critically this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. ghelichkhani et al. 2 ill patients has been evaluated in only a few studies (16, 17). availability of a scoring system that in addition to accuracy, precision, and easy use, leads to facilitation of the nursing care of trauma patients is a necessity. by providing an accurate picture of injury severity, such a system would be able to give a reflection of the outcome of the patient to the health care team. contradicting results exist from comparing gcs and four score in prediction of final outcomes. in a multi-center study, wijdicks et al. showed that four score and gcs do not differ in prediction of inhospital mortality, although they suggested that four score can be a better diagnostic tool for assessing brainstem reflexes and respiratory pattern (17). however, jalali and rezaei showed that four score performs better than gcs in prediction of mortality (18). presence of these contradictions shows the need for carrying out more studies. therefore, the present study was done with the aim of comparing gcs and four score in predicting the mortality of trauma patients. 2. methods 2.1. study design and setting the present prospective diagnostic accuracy study was designed with the aim of comparing the 2 systems of gcs and four score in predicting the outcome of trauma patients hospitalized in icu of 2 hospitals affiliated with shahid beheshti university of medical sciences. for this purpose, data of 90 patients were evaluated in the time interval between february and september 2017. this study was approved by the ethics committee of tehran university of medical sciences and shahid beheshti university of medical sciences. throughout the study, the researchers adhered to the principles indicated in the declaration of helsinki. before inclusion in the study, an informed consent was obtained from the patient or their relative. 2.2. participants over 14 years old trauma patients hospitalized in icu were studied using consecutive sampling. patients with hearing and talking disabilities and with a history of sensorimotor disability were excluded from the study. 2.3. data gathering demographic data (age, sex), trauma mechanism (pedestrian-car accident, motorcycle accident, falling, pedestrian-motorcycle accident, direct trauma, car rollover, and car-car accident), and length of stay in icu were gathered. in addition, a checklist consisting of items used for calculating gcs (evaluation of eye, speech, and motor score) and four score (evaluation of eye, motor, brainstem reflexes, and respiratory pattern score) was also used in this study. data were gathered by 2 trained icu nurses who were completely familiar with data gathering tools. before the initiation of the study, in order to approve inter-rater reliability of the 2 nurses in scoring of gcs and four score, a primary study was performed in which both nurses evaluated both scores simultaneously for the same 15 patients. the agreement rate obtained was 91% (kappa=0.91). 2.4. index test in the present study, predictive values of gcs and four score in prediction of in-hospital mortality of trauma patients were assessed. the details of scoring methods of the 2 mentioned scores have been reported in previous studies (19, 20). gcs and four score of each patient were simultaneously calculated on admission as well as 6, 12 and 24 hours after that. 2.5. reference test death or survival of the patient at the time of discharge from the hospital was used as the reference test. patients were followed until their discharge from the hospital and their living status at the time of discharge was evaluated. 2.6. statistical analysis area under the curves reported for gcs and four score have been 0.78 and 0.84, respectively (21). therefore, by considering 95% confidence interval (α=5%) and power of 90% (β=10%), sample size is calculated as about 90 patients. data were analyzed using stata 14.0 statistical software. descriptive analyses were presented as mean and standard deviation, or frequency and percentage, for quantitative and qualtable 1: demographic and baseline characteristics of the studied patients baseline characteristics value sex female 23(25.6) male 67(74.4) trauma mechanism motorcycle accident 32 (35.6) car accident 22 (24.4) falling 20 (22.2) pedestrian 10 (10.1) other 6 (6.7) vital signs on admission systolic blood pressure (mmhg) 115.4±6.27 diastolic blood pressure (mmhg) 72.5±3.16 heart rate (beat per min) 94.6±0.26 respiratory rate (beat per min) 18.2±9.6 temperature (degree of celsius) 36.9±0.3 oxygen saturation (%) 92.2±9.9 length of stay in icu (days) 7.4±5.9 data were presented as mean ± standard deviation or number (%). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e42 table 2: mean gcs and full outline of unresponsiveness (four) score at different times with 95% confidence interval (ci) survived non survived mean 95% ci mean 95% ci gcs on admission 11.3 10.6 – 12.1 5.5 4.0 – 7.1 after 6 hours 11.7 11.0 – 12.5 5.1 3.9 – 6.3 after 12 hours 11.8 11.1 – 12.5 5.6 4.9 – 6.3 after 24 hours 11.6 10.8 – 12.3 4.0 3.3 – 4.6 four score on admission 12.7 11.8 – 13.6 4.1 1.8 – 6.3 after 6 hours 13.0 12.1 – 13.9 2.7 1.2 – 4.2 after 12 hours 13.9 13.1 – 14.7 3.4 2.0 – 4.8 after 24 hours 13.6 12.7 – 14.4 0.1 0.0 – 0.3 table 3: multiple logistic regression analysis for the values of gcs and four score in predicting the morality of trauma patients with 95% confidence interval (ci) variable odds ratio 95% ci p* glasgow coma scale at admission 0.72 0.53 to 0.98 0.04 6 hours 0.57 0.38 to 0.86 0.007 12 hours 0.28 0.10 to 0.76 0.01 24 hours 0.21 0.06 to 0.75 0.02 four score at admission 0.79 0.62 to 0.99 0.049 6 hours 0.55 0.36 to 0.83 0.004 12 hours 0.43 0.22 to 0.84 0.01 24 hours 0.05 0.02 to 0.08 <0.0001 *: adjusted for age, systolic blood pressure, oxygen saturation, need for intubation and need for sedation. itative factors, respectively. to compare mean score of gcs and four score in dead and alive patients at the evaluated times, two-way repeated measures anova with bonferroni post hoc was applied. in addition, the predictive values of gcs and four score were evaluated in predicting the outcome of patients via drawing receiver operating characteristic (roc) curve. fitness of the model was evaluated using hosmer-lemeshow test and in the end, the mentioned values were compared between the 2 models. in this study, p<0.05 was considered as level of significance. 3. results 3.1. demographic and clinical data in this study, data of 90 trauma patients hospitalized in icu were evaluated. mean and standard deviation of patients’ age was 39.4±17.3 years (74.4% male). the most important mechanisms of trauma were motorcycle (35.6%) and car (24.4%) accidents, and falling from a height more than 3 meters (13.3%). 13.3% of the patients had hypertension, 4.4% had diabetes, 3.3% had neurologic deficiencies, 2.2% had cardiovascular diseases, and 3.3% had other underlying diseases. outcome of hospitalization in icu was death in 21 cases (23.3%) (table 1). the trend of changes in gcs and four score during 24 hours based on death or survival of the patients is presented in table 2. based on these findings mean gcs (df: 1, 87; f=6.58; p=0.01) and four score (df: 1, 88; f=46.64; p<0.001) were lower in those who died compared to those who survived. 3.2. gcs and four score in predicting mortality area under the roc curve calculated for gcs on admission and 6, 12, and 24 hours after that were 0.87 (95% ci: 0.77 to 0.98), 0.91 (95% ci: 0.84 to 0.99), 0.95 (95% ci: 0.90 to 0.99) and 0.97 (95% ci: 0.95 to 1.0), respectively. these values were calculated as 0.88 (95% ci: 0.77 to 0.99), 0.96 (95% ci: 0.92 to 1.0), 0.97 (95% ci: 0.92 to 1.0) and 0.99 (95% ci: 0.97 to 1.0), respectively for four score. comparison of area under the roc curve of gcs and four score showed that this value was not different between the 2 systems in any of the evaluated times of on admission (p=0.68), 6 hours (p=0.13), 12 hours (p=0.18), and 24 hours (p=0.20) after that (figure 1). the correlation between predicted in-hospital mortality and the 2 scales (gcs and four score) was also similar (figure 2). findings resulting from multivariate logistic regresthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. ghelichkhani et al. 4 figure 1: area under the roc curve of glasgow coma scale (gcs) and full outline of unresponsiveness (four) score for predicting the mortality of trauma patients at different times. sion showed that with a decrease in scores of gcs and four score, the probability of mortality increases in trauma patients. range of predicted mortality was similar in both gcs and four score models (table 3). 4. discussion based on the findings of our study, area under the roc curve of both gcs and four score on admission and 6, 12, and 24 hours after that were not different and both scales had the same predictive values in identifying the outcome at the time of discharge. in line with our study, the results of the study by sahin et al. (2015) in evaluation of 105 patients also showed that gcs and four score have similar value in prediction of patient mortality and can be used interchangeably (22). the results of a study by atahar et al. (2017) also showed that gcs and four score have the same predictive value in prediction of in-hospital mortality and mortality within 3 months of discharge among children (23). the findings of gujjar et al. study showed that four score is a better scale compared to gcs for evaluation of changes in level of consciousness in medical wards (24). one of the reasons for the dissimilarity of the results of this study with ours might be their different research environment. the research environment in our study was trauma icu department. in line with our findings, the study by temiz et al. (2016) also showed that four score has the same prediction value as gcs in evaluating the level of consciousness and follow-up of patient’s status in neurosurgery icu (25). in contrast to these findings, the results of the study by nair et al. (2017) showed that there is a statistically significant difference between four score and gcs in estimating the severity of injury in head traumas. they reported that four score is a better index for evaluating the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e42 figure 2: the correlation of glasgow coma scale (gcs) and full outline of unresponsiveness (four) score with in-hospital mortality of trauma patients at different times. level of consciousness in patients with head trauma (26). the results of wolf et al. study (2011) showed that gcs is one of the proper indices in prediction of mortality in emergency medical admission (27). in this study we evaluated gcs and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com p. ghelichkhani et al. 6 four score in 4 points of time: on admission, and 6 hours, 12 hours, and 24 hours after admission. the results showed that the mean and standard deviation of both of these scales were different between those who died and those who survived in the 4 evaluated points of time. in line with these findings were the results of a study by gujjar et al. (2013) that evaluated gcs and four score during the initial 3 days of patients’ hospitalization and showed that there is no significant difference regarding mean value of these scales on the second and third day between dead and survived patients but there is a significant difference between these mean values on the first day (24). 5. limitation this study also had limitations including its small sample size and being performed in 2 trauma centers. using a larger sample size and designing a multicenter study might provide more valuable and reliable results. 6. conclusion the results of our study showed that, gcs and four score have the same value in predicting the mortality of trauma patients. both tools had high predictive power in predicting the outcome at the time of discharge. 7. appendix 7.1. acknowledgements the authors would like to thank all of participants during the different stages of this study. 7.2. funding/support this study was one part of the ms dissertation of the first author, financially supported by tehran university of medical sciences. 7.3. conflict of interest no conflict of interest has been declared by the authors. 7.4. author contribution parisa ghelichkhani, maryam esmaeili, and khatereh seylani designed the study. parisa ghelichkhani participated in data gathering. mostafa hosseini analyzed data. parisa ghelichkhani and maryam esmaeili wrote the first draft and others critically revised it. references 1. saadat s, yousefifard m, asady h, jafari am, fayaz m, hosseini m. the most important causes of death in iranian population; a retrospective cohort study. emergency. 2015;3(1):16. 2. forouzanfar mh, sepanlou sg, shahraz s, besc pn, pourmalek f, lozano r, et al. evaluating causes of death and morbidity in iran, global burden of diseases, injuries, and risk factors study 2010. archives of iranian medicine. 2014;17(5):304. 3. de souza nogueira l, de alencar domingues c, poggetti rs, de sousa rmc. nursing workload in intensive care unit trauma patients: analysis of associated factors. plos one. 2014;9(11):e112125. 4. knaus wa, wagner dp, draper ea, zimmerman je, bergner m, bastos pg, et al. the apache iii prognostic system. risk prediction of hospital mortality for critically ill hospitalized adults. chest journal. 1991;100(6):161936. 5. breslow mj, badawi o. severity scoring in the critically ill: part 1—interpretation and accuracy of outcome prediction scoring systems. chest journal. 2012;141(1):24552. 6. nakhjavan-shahraki b, yousefifard m, faridaalaee g, shahsavari k, oraii a, hajighanbari mj, et al. performance of physiology scoring systems in prediction of inhospital mortality of traumatic children: a prospective observational study. journal of clinical orthopaedics and trauma. 2017;8:s43-s8. 7. ahmadi s, yousefifard m. accuracy of pediatric emergency care applied research network rules in prediction of clinically important head injuries; a systematic review and meta-analysis. international journal of pediatrics. 2017;5(12):6285-300. 8. safari s, yousefifard m, baikpour m, rahimi-movaghar v, abiri s, falaki m, et al. validation of thoracic injury rule out criteria as a decision instrument for screening of chest radiography in blunt thoracic trauma. journal of clinical orthopaedics and trauma. 2016;7(2):95-100. 9. nakhjavan-shahraki b, baikpour m, yousefifard m, nikseresht zs, abiri s, mirzay razaz j, et al. rapid acute physiology score versus rapid emergency medicine score in trauma outcome prediction; a comparative study. emergency (tehran, iran). 2017;5(1):e30. 10. nakhjavan-shahraki b, yousefifard m, hajighanbari mj, karimi p, baikpour m, mirzay razaz j, et al. worthing physiological score vs revised trauma score in outcome prediction of trauma patients; a comparative study. emergency (tehran, iran). 2017;5(1):e31. 11. nakhjavan-shahraki b, yousefifard m, hajighanbari mj, oraii a, safari s, hosseini m. pediatric emergency care applied research network (pecarn) prediction rules in identifying high risk children with mild traumatic brain injury. european journal of trauma and emergency surgery : official publication of the european trauma sothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e42 ciety. 2017;43(6):755-62. 12. nakhjavan-shahraki b, yousefifard m, oraii a, sarveazad a, hajighanbari mj, safari s, et al. prediction of clinically important traumatic brain injury in pediatric minor head trauma; proposing pediatric traumatic brain injury (ptbi) prognostic rule. international journal of pediatrics. 2017;5(1):4127-35. 13. gill m, martens k, lynch el, salih a, green sm. interrater reliability of 3 simplified neurologic scales applied to adults presenting to the emergency department with altered levels of consciousness. annals of emergency medicine. 2007;49(4):403-7. e1. 14. balestreri m, czosnyka m, chatfield d, steiner l, schmidt e, smielewski p, et al. predictive value of glasgow coma scale after brain trauma: change in trend over the past ten years. journal of neurology, neurosurgery & psychiatry. 2004;75(1):161-2. 15. staff t, eken t, wik l, roislien j, sovik s. physiologic, demographic and mechanistic factors predicting new injury severity score (niss) in motor vehicle accident victims. injury. 2013;[in press]. 16. dong pv, cremer ol. limitations of the use of the glasgow coma scale in intensive care patients with nonneurological primary disease: a search for alternatives. critical care. 2011;15(suppl 1):p506-p. 17. wijdicks ef, bamlet wr, maramattom bv, manno em, mcclelland rl. validation of a new coma scale: the four score. annals of neurology. 2005;58(4):585-93. 18. jalali r, rezaei m. a comparison of the glasgow coma scale score with full outline of unresponsiveness scale to predict patients’ traumatic brain injury outcomes in intensive care units. critical care research and practice. 2014;2014:1-4. 19. stead lg, wijdicks ef, bhagra a, kashyap r, bellolio mf, nash dl, et al. validation of a new coma scale, the four score, in the emergency department. neurocritical care. 2009;10(1):50-4. 20. baratloo a, shokravi m, safari s, awat ka. predictive value of glasgow coma score and full outline of unresponsiveness score on the outcome of multiple trauma patients. archives of iranian medicine. 2016;19(3):215. 21. fischer m, ruegg s, czaplinski a, strohmeier m, lehmann a, tschan f, et al. research inter-rater reliability of the full outline of unresponsiveness score and the glasgow coma scale in critically ill patients: a prospective observational study. 2010;14(critical care):r64. 22. sahin as, sahin m, ozturk nk, kizilates e, karsläś b. comparision of gcs and four scores used in the evaluation of neurological status in intensive care units. journal of contemporary medicine. 2015;5(3):167-72. 23. jamal a, sankhyan n, jayashree m, singhi s, singhi p. full outline of unresponsiveness score and the glasgow coma scale in prediction of pediatric coma. world journal of emergency medicine. 2017;8(1):55-60. 24. gujjar ar, jacob pc, nandhagopal r, ganguly ss, obaidy a, al-asmi ar. full outline of unresponsiveness score and glasgow coma scale in medical patients with altered sensorium: interrater reliability and relation to outcome. journal of critical care. 2013;28(3):316.e1-8. 25. temiz nc, kose g, tehli o, acikel c, hatipoglu s. a comparison between the effectiveness of full outline of unresponsiveness and glasgow coma score at neurosurgical intensive care unit patients. turkish neurosurgery. 2016. 26. nair ss, surendran a, prabhakar rb, chisthi mm. comparison between four score and gcs in assessing patients with traumatic head injury: a tertiary centre study. international surgery journal. 2017;4(2):656. 27. wolf ca, wijdicks ef, bamlet wr, mcclelland rl, editors. further validation of the four score coma scale by intensive care nurses. mayo clinic proceedings; 2007: elsevier. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e50 ca s e re p o rt paradoxical embolism in a patient with patent foramen ovale; a case report mohammad khani1, fariba bayat1, atoosheh rohani2∗, mehdi pishgahi 3 1. department of cardiology, shahid beheshti university of medical sciences, tehran, iran. 2. department of cardiology, mashhad university of medical sciences, mashhad, iran. 3. department of cardiology, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. received: june 2018; accepted: july 2018; published online: 8 august 2018 abstract: patent foramen ovale (pfo) is usually asymptomatic; however, it could be quite dangerous for patients with right side clot in which thrombus can transmit the pfo and paradoxically emboli to systemic circulation. here we present a patient with ankle fracture and paradoxical embolus to the brain, who was successfully treated with emergent thrombectomy, inferior vena cava (ivc) filter placement and anticoagulation therapy. despite the high rate of mortality in these patients, fortunately our patient survived with surgical treatment. keywords: venous thrombosis; pulmonary embolism; embolism, paradoxical; patent foramen ovale; thrombolytic therapy © copyright (2018) shahid beheshti university of medical sciences cite this article as: khani m, bayat f, rohani a, pishgahi m. paradoxical embolism in a patient with patent foramen ovale; a case report. emergency. 2018; 6 (1): e50. 1. introduction: simultaneous occurrences of cerebrovascular accident and pulmonary embolism (pe) demonstrates the presence of paradoxical embolism according to the johnson criteria (1). in 25–30 percent of individuals presenting with paradoxical embolism a patent foramen ovale (pfo) could be detected (2). inter-atrial septum has two parts; septum primum and secundum. there is a slit-like opening between the two parts called a pfo. because of low pressure in both atria and anatomical position of the septum secundum there is no significant left-to-right shunting and little shunting in general; however, when the right atrial pressure rises during a physiological condition like as straining, valsalva maneuver or coughing this slit like flap separates and allows right to left shunting, this type of shunting may become more marked in cases with raised right atrial (ra) pressure due to pathologic conditions such as pe. there is also a “so-called” “flow phenomenon” that describes a preferential blood flow from the inferior vena cava towards the atrial septum as a part of the fetal circulation. ∗corresponding author: atoosheh rohani; department of cardiology, mashhad university of medical sciences, mashhad, iran. email: mp_cr1@yahoo.com tel/fax: 00989123387486 far less than 1% have a stroke or other outcome that results in the need to have the pfo closed. there are some case reports of coexistence of paradoxical emboli with pe systemic embolism and dvt, especially in patients with “hybrid defect”, which is defined as fenestrated secundum atrial septal defect with septal aneurysm (3). 2. case presentation: a 60-year-old female was admitted to our hospital for left ankle and right knee fracture. she underwent orthopedic surgery and was discharged in stable medical condition with administration of low molecular weight heparin (lmwh) on a daily basis. she was asymptomatic and was in healthy medical condition, she denied any symptoms such as dyspnea associated with postural change. she was bed ridden at home, with irregular lmwh injection. forty five days later she presented with convulsion, right side hemiplegia, aphasia and decreased level of consciousness. her past medical history included systemic hypertension and she was not on any regular medication. on admission she was confused, had tachypnea and tachycardia and a pulse rate of 120 beats per minute. her blood pressure was 105/75 mmhg. the oxygen saturation was reduced at 85% in room air. she had total loss of strength in right upper and lower extremities and was aphasic. a neurothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. khani et al. 2 figure 1: clot straddled in patent foramen ovale in transesophageal echocardiography (tee) bicaval view. logical examination showed aphasia and babinski’s sign on the right side. heart and lung examination were unremarkable. electrocardiogram showed right axis deviation and inverted t waves in the anterior leads (v1-v3). echocardiography imaging revealed mild right ventricular (rv ) dilatation and mild impaired rv systolic function and large thrombus crossing the ra to the left atrium (la) via inter-atrial septum. a trans-esophageal echocardiogram revealed a large ra clot extending through a pfo into the la, entrapped in foramen ovale as well as right pulmonary artery thrombus (figure 1). atrial septal aneurysm and pulmonary hypertension with pulmonary arterial pressure of 45mmhg were evident. the chest computed tomography (ct) angiography showed a massive thrombus in the main right and left pulmonary artery. doppler study of her lower legs showed signs of deep vein thrombosis in right superficial femoral and anterior tibialis vein. brain ct scan demonstrated hypodensity in left frontal, temporal and parietal lobes consistent with middle cerebral artery related stroke. patient underwent emergent surgical removal of ra, la, right and left pulmonary arteries and surgical closure of pfo. to reduce the risk of further emboli, the temporary ivc filter was replaced. she had an uneventful postoperative course and was discharged eight days after surgery. our patient is alive but aphasic and hemiplegic one year after surgery. patient had signed informed consent to be presented as case report. 3. discussion less than 2% of all cases of systemic arterial emboli are paradoxical (4). as high as 35% of the general population have a pfo, which is the most common cardiac defect in association with paradoxical embolism (5). there are some reports, which demonstrate that presence of pfo is an important predictor of adverse outcome and la dysfunction, which leads to thrombi formation in la (6, 7). when a patient presents with multi-vascular arterial embolism, not only the transthoracic echo, but also the trans-esophageal and even intra-cardiac echocardiography is essential to differentiate between pfo, flat asd and hybrid defects. there are no clear guidelines based on randomized trials for treatment of paradoxical embolism. surgical embolectomy with exploration of the right chambers and the pulmonary arteries under complete cardiopulmonary bypass is the classic treatment; however, there are reports (7-9) of successful medical treatment of ra and la clot questioning whether mechanical closure of pfo should be indicated. since older patients are more prone to rapid change of right heart pressure, we decided to send our patient to the operating room considering the large clot burden, contraindications to thrombolytic, her age, and the risk of relapse. according to previous reports, in-hospital mortality is as high as 44.7 % (10-12). 4. conclusion: we described the diagnosis and successful surgical treatment of a severe form of venous thromboembolic disease with thrombi in transit getting complicated by paradoxical embolus to cerebral arteries in an aged woman. however, there are no clear guidelines based on randomized trials for therapy of paradoxical embolism. clot removal by cardiopulmonary bypass surgery as shown in our case, could be considered in treatment of paradoxical embolism. 5. appendix 5.1. acknowledgements none. 5.2. author’s contribution all authors passed the four criteria for authorship contribution based on recommendations of the international committee of medical journal editors. 5.3. conflict of interest none. 5.4. funding none. references 1. johnson bi. paradoxical embolism. journal of clinical pathology. 1951;4(3):316-32. 2. hara h. patent foramen ovale [updated jan 25, 2018.]. 3. rigatelli g, rigatelli a. closing patent foramen ovale in cryptogenic stroke: the underscored importance of this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e50 other interatrial shunt variants. world journal of cardiology. 2015;7(6):326. 4. d’audiffret a, shenoy s, ricotta j, dryjski m. the role of thrombolytic therapy in the management of paradoxical embolism. cardiovascular surgery. 1998;6(3):302-6. 5. konstantinides s, geibel a, kasper w, olschewski m, blãijmel l, just h. patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. circulation. 1998;97(19):1946-51. 6. seiler c. patent foramen ovale (pfo): is there life before death in the presence of pfo? european journal of clinical investigation. 2015;45(8):875-82. 7. goldhaber sz. unsolved issues in the treatment of pulmonary embolism. thrombosis research. 2001;103(6):v245-v55. 8. zanchetta m, rigatelli g, pedon l, zennaro m, carrozza a, onorato e. catheter closure of perforated secundum atrial septal defect under intracardiac echocardiographic guidance using a single amplatzer device: feasibility of a new method. the journal of invasive cardiology. 2005;17(5):262-5. 9. caretta g, robba d, bonadei i, teli m, fontanella b, vizzardi e, et al. multiorgan paradoxical embolism consequent to acute pulmonary thromboembolism with patent foramen ovale: a case report. cases journal. 2009;2(1):8358. 10. chant h, mccollum c. stroke in young adults: the role of paradoxical embolism. thrombosis and haemostasis. 2001;85(01):22-9. 11. chartier l, bera j, delomez m, asseman p, beregi jp, bauchart j-j, et al. free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. circulation. 1999;99(21):2779-83. 12. pishgahi m, alirezaei t, hajimoradi b, nekooghadam sm, shahi s. systemic fibrinolytic therapy in the presence of absolute contraindication; a case series. emergency. 2018;6(1):25. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction: case presentation: discussion conclusion: appendix references archives of academic emergency medicine. 2021; 9(1): e1 https://doi.org/10.22037/aaem.v9i1.891 or i g i n a l re s e a rc h clinical predictors of emergency department revisits within 48 hours of discharge; a case control study panvilai tangkulpanich1, chaiyaporn yuksen1∗, wanchalerm kongchok1, chestsadakon jenpanitpong1 1. department of emergency medicine, ramathibodi hospital, mahidol university, bangkok, thailand. received: october 2020; accepted: october 2020; published online: 5 november 2020 abstract: introduction: emergency department (ed) revisits increase overcrowding and predicting which patients may need to revisit could increase patient safety. this study aimed to identify clinical variables that could be used to predict the probability of revisiting ed within 48 hours of discharge. methods: a retrospective case-control study was conducted between july 2018 and january 2019 at the emergency medicine department in ramathibodi hospital, bangkok, thailand. patients who revisited the ed within 48 hours of discharge (case group) and patients who did not (control group) participated. the predictive factors for ed revisit were identified through multivariate logistic regression analysis. results: the case group consisted of 372 patients, who revisited the ed within 48 hours, and the control group consisted of 1488 patients. the most common reason for revisiting the ed was recurring gastrointestinal illness, in 107 patients (28.76%). according to the multivariate data analysis , five factors influenced the probability of revisiting the ed: age of more than 60 years (p < 0.001, or = 2.04, 95%ci: 1.51-2.77), initial emergency severity index (esi) triage level of 2 (p = 0.007, or = 1.20, 95%ci: 0.93-1.56), ed stay duration of 4 hours or longer (p = 0.013, or = 1.12, 95%ci: 0.87-1.44), body temperature of ≥37.5◦c on discharge (p = 0.034, or = 1.34, 95%ci: 1.00-1.80), and pulse rate of less than 60 (or = 1.55, 95%ci: 0.87-2.77) or more than 100 beats/minute (or = 1.53, 95%ci: 1.10-2.11) (p = 0.011). conclusion: according to the findings, the most important and independent predictive factor of ed revisit within 48 hours of discharge were, age ≥ 60 years, esi triage level 2, ed length of stay ≥ 4 hours, temperature ≥ 37.5 c, and 60 > pulse rate ≥ 100 beats/minute. keywords: emergency service, hospital; patient discharge; clinical decision rules; triage; thailand cite this article as: tangkulpanich p, yuksen c, kongchok w, jenpanitpong c. clinical predictors of emergency department revisits within 48 hours of discharge; a case control study. arch acad emerg med. 2021; 9(1): e1. 1. introduction emergency department (ed) overcrowding is a significant problem in tertiary care hospitals. many factors contribute to this problem, such as an increase in the number of patients who come to the ed and insufficient beds for inpatients. as a result of overcrowding, waiting time for treatment in ed increases, and specific resources are used unnecessarily (1). the average time between discharge and revisit to the ed has not yet been defined. most authors refer to it as 24 to 72 hours (2-5). revisit within 72 hours is a widely accepted quality assurance tool. the overall probability of revisiting the ed is approximately 3% in most studies and patients who revisit are considered to have a high risk for complications ∗corresponding author: chaiyaporn yuksen; 270 rama vi road, thung phaya thai, ratchathewi, bangkok, thailand, 10400. tel: (+66)8-94726911, emails: chaipool0634@hotmail.com, panvilai.tan@mahidol.edu, orcids: http:// 0000-0002-2922-2761 and death (5). many researchers have analysed the factors involved in revisiting the ed: those related to the patient’s illness, ed treatment, and medical service systems (6-8). factors such as the nature of the disease, medical error, patient satisfaction (9), and inadequate assessment or treatment in the first ed visit (5) may account for revisits. if the interval is short (3–7 days), the cause may be related to improper treatment, treatment errors, or adverse events after treatment (10). a review of these causes is essential for quality assurance of inpatient care. these can be resolved by educating patients about the diagnosis and treatment (11). predicting which patients are likely to revisit the ed after discharge would help plan and adequately manage resources. clinicians must identify essential variables to assess the probability of readmission after the discharge of a patient (12). health care organizations have access to comprehensive medical histories, convenient for developing and testing tools to assess the probability of revisiting the ed after disthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. tangkulpanich et al. 2 charge (13). this study aimed to identify clinical variables that could be used to predict the probability of revisiting the ed within 48 hours of discharge. 2. methods 2.1. study design and setting a retrospective case-control study was conducted from july 2018 to january 2019, at the ed of ramathibodi hospital, a university-affiliated super tertiary care hospital in bangkok, thailand. patients who revisited the ed within 48 hours of discharge (case group) and patients who did not (control group) were compared and the predictive factors of ed revisit were identified through multivariate logistic regression analysis. the ethics committee approved this study on human rights related to research involving human subjects by faculty of medicine, ramathibodi hospital, mahidol university, bangkok, thailand (ethics code: mura2018/377). 2.2. participants the patients who revisited the ed within 48 hours after discharge were recruited to comprise a case group. the patients who did not revisit within 48 hours after discharge were recruited to include a control group. we collected the control group from the emergency medical record (emr) program. we excluded patients suffering from trauma, patients younger than 15 years of age, and patients who revisited with a different problem. 2.3. data gathering the following data, including baseline characteristics, clinical factors, and possible effective factors of revisit were collected: gender, age, initial triage level based on emergency severity index (esi), chief complaint, first ed visit length of stay (los), vital signs before discharge (body temperature, systolic blood pressure, and pulse rate). patients revisiting ed were defined as patients who returned to the ed with the same related symptom within 48 hours after ed discharge (14). 2.4. statistical analysis we used stata version 12 software (statacorp, college station, tx, usa) to conduct a two-sample comparison of proportions with the following assumptions: alpha = 0.05 (onesided), power = 0.8, and n2/n1 = 4. the sample size that we planned to recruit was approximately 372 patients who revisited the ed and 1488 who did not. the possible predictors of revisiting the ed within 48 hours after discharge were compared between the 2 groups to identify differences (p-value) in clinical characteristics using independent t-test and exact probability test. the predictive factors were identified using univariate and multivariate logistic regression analysis and were presented with area under the receiver operating characteristic (auroc) curve and 95% confidence interval (95% ci) and odds ratio (or). calibration of the prediction was presented using hosmer–lemeshow goodness-of-fit test. 3. results 3.1. baseline characteristics of participants the average number of patients who revisited within 24 and 48 hours in the studied ed was 40 cases per month (0.02% of patients visiting the ed) and 80 cases per month (0.01% of patients visiting the ed), respectively. of the 1582 patients who revisited the ed during the study period, 1210 were not eligible according to the research criteria (322 were younger than 15 years of age, 218 patients were suffering from trauma, and 670 revisited with a different problem). therefore, the case group consisted of 372 patients who revisited the ed within 48 hours after being discharged, and the control group consisted of 1488 patients who did not revisit the ed (figure 1). the most common reason for revisiting the ed was recurring gastrointestinal illness, in 107 patients (28.76%). most of the patients revisiting the ed within 48 hours after discharge were in esi triage level 2 (16%), level 3 (40%), and level 4 (44%), respectively. table 1 compares the baseline characteristics of patients between revisited and non-revisited cases. a significant difference was observed between groups regarding age group (p < 0.001), initial esi triage level (p = 0.007), first ed visit length of stay (p = 0.013), discharge time body temperature (p = 0.034), and pulse rate (p = 0.011). 3.2. modelling according to the multivariate regression analysis (table2), five factors influenced the probability of revisiting the ed: age of more than 60 years (p < 0.001, or = 2.04, 95%ci: 1.512.77), initial esi triage level of 2 (p = 0.007, or = 1.20, 95%ci: 0.93-1.56), duration of ed stay of 4 hours or longer (p = 0.013, or = 1.12, 95%ci: 0.87-1.44), body temperature of ≥37.5◦c on discharge (p = 0.034, or = 1.34, 95%ci: 1.00-1.80), and pulse rate of less than 60 (or = 1.55, 95%ci: 0.87-2.77) or more than 100 beats/minutes (or = 1.53, 95%ci: 1.10-2.11) (p = 0.011). the significant variables were scored considering their coefficient measures to divide patients into three groups: those with scores of 0 (low probability of revisiting ed), those with scores of 1 to 7 points (moderate probability of revisiting ed), and those with scores > 7 points (high probability of revisiting ed) (table 2). the positive likelihood ratio of score > 7 for returning to the ed within 48 hours after discharge was 1.48 (table 3). the auc of the model in predicting the need for ed revisit was 61% (95%ci: 58-67; figure 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e1 table 1: comparing the baseline characteristics of patients who revisited and those who did not revisit the emergency department (ed) within 48 hours after discharge variables revisited (n = 372) not-revisited (n = 1488) p n % n % gender male 166 44.62 592 39.78 0.099 female 206 55.38 896 60.22 age (years) ≤40 85 22.85 499 33.53 40-60 87 23.29 382 25.67 <0.001 > 60 200 53.76 607 40.79 initial triage level level 2 120 32.26 376 25.27 0.007 level 3, 4, or 5 252 67.74 1,112 74.73 underlying diseases infectious 101 27.15 395 26.55 0.844 neurologic 23 6.18 170 11.42 0.002 gastroenterological 107 28.76 360 24.19 0.071 respiratory 43 11.56 137 9.07 0.167 cardiovascular 39 10.48 144 9.68 0.627 endocrinologic 4 1.08 16 1.08 1.000 haematologic 4 1.08 16 1.08 1.000 nephrological 28 7.53 72 4.84 0.053 ob-gynaecologic 13 3.49 38 2.55 0.373 musculoskeletal 10 2.69 142 9.54 <0.001 transportation to ed ambulance 9 2.42 16 1.08 0.072 walk in 363 97.58 1,472 98.92 first ed visit, length of stay (hours) <4 218 58.60 976 65.59 0.013 ≥4 154 41.40 512 34.41 discharge body temperature (degrees celsius) ≥37.5 95 25.54 302 20.30 0.034 systolic blood pressure (mmhg) <90 0 0 1 0.07 90–140 243 65.32 977 65.66 0.922 ≥140 129 34.68 510 34.27 pulse rate (bpm) <60 277 74.46 1,211 81.38 60–100 17 4.57 45 3.02 0.011 >100 78 20.97 232 15.59 4. discussion the risk factors that cause patients to revisit to the ed within 48 hours after discharge were found to be age of more than 60 years, initial esi triage level of 2 (no patient triage in level 1 revisit because every patient need to admission from ed), 4 hours or longer duration of ed stay in the first visit, body temperature of ≥37.5◦c on discharge, and pulse rate of less than 60 or more than 100 beats/minutes on discharge. the rate of revisit within 48 hours was 0.01% in our study. the result was better than the other studies that reported the 48-hour revisit rate to be 0.19% (4, 7). the patient discharge process in ramathibodi hospital would begin based on the opinion of the senior emergency resident and emergency staff to reduce the revisit rate. misdiagnosis was the most common cause of ed revisits (14); patient discharge by the experienced emergency staff was the key to lowering the revisit rate. the study by sri-on (14), which evaluated the risk factors that lead patients to revisiting the ed within 48 hours after discharge in thailand, showed that most patients who revisit were older than 60 years and the majority of causative diseases were related to the digestive system; these findings are similar to our results. the first patient screening at triage revealed that patients with an urgent triage level were most likely to revisit within 48 hours (the urgent level was defined as esi level 3 in this study). these findings are different from our results. in our hospital, patients with esi level 2 are this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. tangkulpanich et al. 4 table 2: multivariate regression analysis of predictors of emergency department (ed) revisit within 48 hours after discharge predictors odds ratio 95% ci p value coefficient score age (years) <40 reference – – – 0 40–60 1.39 1.00–1.95 0.052 0.33 3 ≥60 2.04 1.51–2.77 <0.001 0.72 7 esi initial triage level level 2 1.20 0.93–1.56 0.158 0.19 1.5 level 3, 4 , or 5 reference – – – 0 first ed visit length of stay (hour) <4 reference – – – 0 ≥4 1.12 0.87–1.44 0.376 0.11 1 *temperature ≥37.5◦c no reference – – – 0 yes 1.34 1.00–1.80 0.053 0.29 2.5 *pulse rate (bpm) <60 1.55 0.87–2.77 0.139 0.44 4 60–100 reference – – – 0 ≥100 1.53 1.10–2.11 0.010 0.42 4 *vital sign at the time of discharge; esi: emergeing severity index; or: adjusted odds ratio; ci: confidence interval; ed: emergency department. figure 1: the process of selecting the study population. ed: emergency department. mostly treated in ed, and the length of stay in ed for more than 4 hours because there was no available bed for admission. some of the patients with esi level 2 stayed in the ed for more than 4 hours as no bed was available, some of which were discharged by the emergency physician. many studies used the identification of seniors at risk (isar) for identifying elderly patients at risk of adverse outcomes and predicting hospital readmission after ed discharge. however, the isar was unable to predict 48 hours revisit (15, 16). this study used the variables that were available bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e1 figure 2: area under the receiver operator characteristic curve of the model for predicting the probability of revisiting the emergency department within 48 hours after discharge. table 3: groups of patients according to scores indicating the probability of returning to emergency department (ed) within 48 hours probability score revisited no revisit plr 95% ci p n % n % low 0 26 10.10 230 89.90 0.62 0.42–0.91 0.006 moderate 1–7 159 17.45 752 82.54 0.85 0.74–0.96 0.004 high >7 187 26.98 506 73.02 1.48 1.31–1.67 <0.001 ci: confidence interval; plr: positive likelihood ratio. fore ed discharge, so they can be evaluated by an emergency nurse or doctor to predict ed revisit. elderly patients, patients who are initially in triage level 2 when they visit the ed, those with a length of stay of more than 4 hours in ed, and those who have had a high body temperature, or abnormal pulse rate before discharge had a high probability of ed revisits. if a patient’s score is more than 0 points before discharge, special attention should be given; scores of 1 to 7 points indicate a moderate probability of revisit to the ed within 48 hours, and scores more than 7 show a high likelihood of returning (table 3). it may be necessary for patients with scores between 1 and 7 to be monitored according to the indications. patients with high scores should be repeatedly evaluated before discharge. at the time of discharge, it is necessary to make an appointment to regularly monitor the patient within the following 24 to 48 hours to reduce the risk of complications that may result in a return to the ed after discharge. these patients may require more treatments than delivered in the ed. in the ed of our hospital and those of large general hospitals in thailand, the majority of patients admitted are older than this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem p. tangkulpanich et al. 6 60 years of age, and during peak periods, patients may spend extra time in the ed, including waiting times. laboratory examination, investigation of symptoms and treatment may take more than 4 hours; therefore, if the prediction score for probability of revisit to the ed after discharge is used to assess a patient before discharge, most patients will have high scores. the generated score may, therefore, be used as part of deciding whether to discharge the patient or not. 5. limitations there are some limitations to this study. ramathibodi hospital is a university hospital whose ed treats a large number of patients. the number of inpatient beds is quite limited; therefore, some patients who need to stay in the hospital may have to be referred to other centers for treatment or be discharged home. for patients who go to other hospitals, their data may not be available to ramathibodi hospital, and so it is impossible to determine certain variables that may be statistically significant. the tool’s predictive accuracy is 61%, which is low. this may be attributable to the fact that our sample was small. a larger population and investigation in multiple educational institutions may help increase the predictive accuracy of the tool. 6. conclusion according to the findings, the most important and independent predictive factor of ed revisit within 48 hours of discharge were, age ≥ 60 years, esi triage level 2, ed length of stay ≥ 4 hours, temperature ≥ 37.5 c, and 60 > pulse rate ≥ 100 beat/minutes. 7. declarations 7.1. acknowledgements none. 7.2. author contribution pt and cy conceptualized the research idea, collected data, performed the analysis and wrote the first draft of the manuscript. cy and wk provided oversight and supervision of the research. wk and cj contributed in the data acquisition, analysis, or interpretation. all authors read and approved the final manuscript. 7.3. funding/support none. 7.4. conflict of interest none. references 1. fan j-s, kao w-f, yen dh-t, wang l-m, huang c-i, lee ch. risk factors and prognostic predictors of unexpected intensive care unit admission within 3 days after ed discharge. the american journal of emergency medicine. 2007;25(9):1009-14. 2. hu s-c. analysis of patient revisits to the emergency department. the american journal of emergency medicine. 1992;10(4):366-70. 3. keith kd, bocka jj, kobernick ms, krome rl, ross ma. emergency department revisits. annals of emergency medicine. 1989;18(9):964-8. 4. abualenain j, frohna wj, smith m, pipkin m, webb c, milzman d, et al. the prevalence of quality issues and adverse outcomes among 72-hour return admissions in the emergency department. the journal of emergency medicine. 2013;45(2):281-8. 5. cheng s-y, wang h-t, lee c-w, tsai t-c, hung c-w, wu k-h. the characteristics and prognostic predictors of unplanned hospital admission within 72 hours after ed discharge. the american journal of emergency medicine. 2013;31(10):1490-4. 6. pierce jm, kellerman al, oster c. “bounces”: an analysis of short-term return visits to a public hospital emergency department. annals of emergency medicine. 1990;19(7):752-7. 7. wu c-l, wang f-t, chiang y-c, chiu y-f, lin t-g, fu l-f, et al. unplanned emergency department revisits within 72 hours to a secondary teaching referral hospital in taiwan. the journal of emergency medicine. 2010;38(4):512-7. 8. kelly a, chirnside a, curry c. an analysis of unscheduled return visits to an urban emergency department. the new zealand medical journal. 1993;106(961):334-6. 9. nunez s, hexdall a, aguirre-jaime a. unscheduled returns to the emergency department: an outcome of medical errors? bmj quality & safety. 2006;15(2):102-8. 10. jin b, zhao y, hao s, shin ay, wang y, zhu c, et al. prospective stratification of patients at risk for emergency department revisit: resource utilization and population management strategy implications. bmc emergency medicine. 2016;16(1):10. 11. lerman b, kobernick ms. return visits to the emergency department. the journal of emergency medicine. 1987;5(5):359-62. 12. kansagara d, englander h, salanitro a, kagen d, theobald c, freeman m, et al. risk prediction models for hospital readmission: a systematic review. jama. 2011;306(15):1688-98. 13. hao s, jin b, shin ay, zhao y, zhu c, li z, et al. risk prediction of emergency department revisit 30 this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2021; 9(1): e1 days post discharge: a prospective study. plos one. 2014;9(11):e112944. 14. sri-on j, nithimathachoke a, tirrell gp, surawongwattana s, liu sw. revisits within 48 hours to a thai emergency department. emergency medicine international. 2016;2016. 15. asomaning n, loftus c. identification of seniors at risk (isar) screening tool in the emergency department: implementation using the plan-do-study-act model and validation results. journal of emergency nursing. 2014;40(4):357-64. e1. 16. de almeida tavares jp, sá-couto p, boltz m, capezuti e. identification of seniors at risk (isar) in the emergency room: a prospective study. international emergency nursing. 2017;35:19-24. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2018; 6 (1): e52 or i g i n a l re s e a rc h correlation of hyperchloremic metabolic acidosis and renal function in critically ill patients of emergency department: an observational study mauro giordano1∗, tiziana ciarambino1, pietro castellino2, lorenzo malatino2, giuseppe signoriello1, giuseppe paolisso1, luigi elio adinolfi1 1. department of medical, surgical, neurological, metabolic and geriatrics sciences, university of campania “l. vanvitelli”, italy. 2. department of clinical and experimental medicine, university of catania, catania, italy. received: may 2018; accepted: august 2018; published online: 25 august 2018 abstract: introduction: early detection is crucial for prompt management of acute kidney injury (aki) patients in emergency department (ed). this study aimed to investigate the usefulness of hyperchloremic metabolic acidosis (hcma) levels in this regard. methods: in this retrospective observational study, > 18 years old critically ill patients presenting to ed of marcianise hospital, italy, were divided into non-aki and aki group according to kdigo guideline. the level of hcma ((arterial ph x bicarbonate)/chloride) was compared between groups and correlation of hcma with estimated glomerular filtration rate (e-gfr) in arf patients was evaluated. results: 134 patients with the mean age of 76.5 ± 3.1 years were enrolled (64 non-aki and 70 aki; 64% female). two groups were similar regarding mean age (p = 0.251), sex (p = 0.091), apachii score (p = 0.215), charlson comorbidity index (p= 0.187), and body mass index (p = 0.129). the mean hcma level was 1.98 ± 0.09 in the non-aki group and 1.56 ± 0.07 in the aki group (p=0.039). there was a positive correlation between hcma and e-gfr levels in aki group (r: 0.467, p=0.0092). conclusion: if confirmed and validated in a future study, abg derived formula for hcma may be a useful tool for early detection of aki patients in emergency department. keywords: acute kidney injury; hyperchloremic metabolic acidosis; emergency department; renal function © copyright (2018) shahid beheshti university of medical sciences cite this article as: giordano m, ciarambino t, castellino p, malatino l, signoriello g, paolisso g, elio adinolfi l. correlation of hyperchloremic metabolic acidosis and renal function in critically ill patients of emergency department: an observational study. emergency. 2018; 6(1): e52. 1. introduction a cute kidney injury (aki) is a frequent and potentially life-threatening syndrome, with high costs for patients and the healthcare systems (1). overall, 5.5% of all emergency department patients had acute kidney injury in one study (2). aki is defined as a rise in creatinine, 50% from its baseline value, and/or a fall in the glomerular filtration rate (gfr) by 25%, and/or a decrease in urine output reaching less than 0.5 ml/kg/h for 6 h or more (3). aki in patients is associated with higher mortality. patients with severe sepsis and septic shock exhibit a complex metabolic acidosis ∗corresponding author: mauro giordano; department of medical, surgical, neurological, metabolic and geriatrics sciences, university of campania, l. vanvitelli, italy. email: mauro.giordano@unicampania.it upon intensive care unit admission, caused predominantly by hyperchloremic acidosis, which is more pronounced in non-survivors (4). normally, the major renal defense against metabolic acidosis is the net urinary excretion of strong anions, such as chloride, and the retention of strong cations (5). this mechanism becomes impaired in aki patients. an early diagnosis is crucial for prompt management of aki to anticipate acute renal dysfunction. the purpose of this study was to investigate the usefulness of hypercloremic metabolic acidosis (hcma) levels evaluated, using an arterial blood gas (abg) analysis derived formula, for early suspicion of aki in emergency department (ed). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. giordano et al. 2 2. methods 2.1. study design and setting in the present retrospective observational study, eligible patients who were admitted to university hospital of marcianise, italy, from january 2017 to march 2017, were evaluated regarding hcma level and its’ correlation with renal function. ethical committee of north campania approved the protocol of the present study and all researchers adhered to the principles of the helsinki declaration during the study period. additionally, a consent form was obtained from patients. 2.2. participants adult (>18 years old) critically ill patients (acute physiology and chronic health evaluation (apache ii) index >18) in emergency department were subdivided in the non-aki (with normal creatinine levels and gfr > 90 ml/min/1.73 m2) and the aki group according to kdigo guideline. aki patients were defined as patients whose serum creatinine had increased to ≥ 0.3 mg/dl (26.5 micrmol/l) within 48 hours or 1.5-fold from the baseline, which was known or presumed to have occurred in the preceding 7 days, with decrease in urine output, according kdigo guidelines (3,8). adults with chronic kidney disease or need for renal replacement therapy, those not giving consent, less than 18 years of age, history of acute gastrointestinal and post-operative patients were excluded. the acute physiology and chronic health evaluation (apache ii) score and charlson comorbidity index (cci) (6, 7) were calculated from the patient charts. 2.3. data gathering and measurements demographic and clinical characteristics, patient diagnoses, procedures (e.g. laboratory tests), treatments/interventions and patient outcomes were extracted from patients’ profiles by an emergency medicine specialist who was responsible for data gathering and patients were enrolled using random sampling method. glomerular filtration rate (gfr) was evaluated via ckdepidemiology collaboration (ckd-epi) equation (8). serum levels of albumin, creatinine and various electrolytes, including na, k, ca, mg, cl and hpo4, were recorded for each patient. blood ph and the partial pressures of oxygen and carbon dioxide in the blood (pao2 and paco2) were measured using a rapidlab blood gas analyzer (gemr premiertm 4000 plus). hcma was evaluated in emergency department, using the following formula: ((ph x hco3-) / cl −), where ph is the arterial ph, hco3is the arterial bicarbonate concentration and cl− is the arterial chloride concentration, as reported by abg analysis, on admission to the emergency department. figure 1: linear positive correlation between hyperchloremic metabolic acidosis (hcma) and estimated glomerular filtration rate (e-gfr) levels in aki group (r: 0.467, p=0.0092). 2.4. statistical analysis data analyses were performed using spss, version 19.0 (ibm corp, armonk, ny). statistical significance was set at p<0.05 for all procedures. analyses of abg were made using a nonparametric u-test by mann-whitney for independent sample. data are presented as percentage and mean ± standard error (se). 3. results 134 patients with the mean age of 76.5 ± 3.1 (68-85) years were enrolled (64 non-aki and 70 aki; 64% female). baseline characteristics of studied patients are reported in table 1. two groups were similar regarding mean age (p = 0.251), sex (p = 0.091), apachii score (p = 0.215), charlson comorbidity index (p= 0.187), and body mass index (p = 0.129). table 2 summarizes the abg, electrolyte findings of studied patients. the mean hcma level was 1.98 ± 0.09 in the non-aki group and 1.56 ± 0.07 in the aki group (p=0.039). figure 1 shows the correlation of hcma and e-gfr levels in aki patients. there was a positive correlation between hcma and e-gfr levels in aki group (r: 0.467, p=0.0092). 4. discussion in this paper we reported the differences of hcma levels in non-aki and aki patients in the emergency department. in aki patients a significant association between abg derived hyperchloremic metabolic acidosis state and e-gfr was found. aki is associated with higher mortality in emergency patients (9, 10). it has been reported that hyperchloremic acidosis due to the intraoperative chloride load also has an important role in deterioration of renal function (11). thus, early identification of aki patients is crucial for their prompt management. acute kidney injury can lead to hyperchloremic metabolic acidosis especially when the glomerular filtration rate is between 30 to 59 ml/min (stage iii) (12, 13). hcma has been reported in aki patients this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e52 table 1: baseline characteristics of studied patients variables non-aki (n=64) aki (n=70) p value sex male 22 (34.3) 26 (37.1) 0.091 female 42 (65.7) 44 (62.9) age (years) mean± se 75±4 77±3 0.251 apache ii score mean± se 22±3 24±4 0.215 charlson comorbidity index mean± se 4.0 ±1.8 4.0 ±1.3 0.187 bmi (kg/m2 ) mean± se 21.2 ± 6.0 22.3 ± 5.0 0.129 serum creatinine (mg/dl) mean± se 0.79 ± 0.02 2.06 ± 0.01 0.0091 e-gfr (ml/min/1.73 m2 ) mean± se 91.3 ± 0.45 33.4 ± 0.25 0.0087 comorbid disease diabetes 22 (31) 33 (47) 0.041 hypertension 44 (59) 35 (50) 0.101 cirrhosis 2 (3) 5 (10) 0.037 copd 6 (10) 8 (11) 0.180 heart failure 11 (17) 15 (21) 0.140 data are presented as mean ± standard error (se) or number (%). apache: acute physiology and chronic health evaluation; bmi: body mass index; copd: chronic obstructive pulmonary disease. table 2: laboratory findings of studied patients variables non-aki (n=64) aki (n=70) p value arterial blood gas parameters ph 7.44 (7.43-7.46) 7.35 (7.35-7.41) 0.131 pco2 43 (41-44) 45 (42-44) 0.110 po2 65 (61-70) 60 (62-71) 0.197 hco3 25.4 (24.5-26.3) 22.5 (21.3-23.7) 0.021 serum electrolyte na+ 136 (135-139) 137 (135-140) 0.199 k+ 4.5 (4.1-5.1) 5.0 (4.5-5.3) 0.213 cl− 95.3 (90.6-102.1) 106.4 (104.2-108.8) 0.046 (ph x hco3 -) / clhcma 1.98 (1.73-2.08) 1.56 (1.48-1.65) 0.039 data are presented with 95% confidence interval. hcma: hyperchloremic metabolic acidosis level. (4). in fact, to maintain normal ph, the kidneys have to perform two physiological functions. the first is to reabsorb all the filtered hco3-. the second is to excrete the daily h + load (14). in particular, during the early phases of aki, progressive hyperammonemia results in hyperchloremic metabolic acidosis because of impairment in renal ammonia excretion (15). in the course of aki there are no classic physical signs and symptoms in the early stage to alert the clinician of ongoing injury. identifying individuals with suspicion for developing aki in the ed is of increasing interest. in fact, the present data suggest that the abg derived formula, for evaluation of hcma state, may have a potential to be used as a screening test, for early diagnosis of aki in emergency patients. these data are crucial, because actually the diagnosis of aki is usually based on changes in serum creatinine. in this regard, serum creatinine is a less rapid indicator of acute renal dysfunction and it may lead to a delay in the diagnosis of aki. on this note, we found a linear positive correlation between the levels of hcma, as evaluated by the abg derived formula, and the impairment of renal function (e-gfr). this is the first study that shows such an association in aki patients in ed. if confirmed and validated in a future study, the use of abg derived formula for hcma may represent a useful tool for early detection of aki in the emergency department. it seems that hcma level may be a useful tool for the early detection of aki within the first few hours of admission. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. giordano et al. 4 5. limitation limitations of the present study are mainly represented by the retrospective study design. in this regard, a future large prospective study may be needed to confirm the present findings. 6. conclusion this is the first report that shows an association between hcma level and aki in emergency department patients. if confirmed and validated in a future study, the use of abg derived formula for hcma may represent a useful tool for early detection of aki patients in emergency department. 7. appendix 7.1. acknowledgements none. 7.2. author contribution mauro giordano and tiziana ciarambino designed the study. pietro castellino, lorenzo malatino, giuseppe signoriello, giuseppe paolisso, luigi elio adinolfi participated in acquisition and management of data. all authors approved final version of the manuscript to be published and are accountable for all aspects of the work. 7.3. funding/support this research has not been supported. 7.4. conflict of interest the authors declare no conflicts of interest. references 1. li pkt, burdmann ea, mehta rl. acute kidney injury: global health alert. arab journal of nephrology and transplantation. 2013;6(2):75-81. 2. scheuermeyer fx, grafstein e, rowe b, cheyne j, grunau b, bradford a, et al. the clinical epidemiology and 30-day outcomes of emergency department patients with acute kidney injury. canadian journal of kidney health and disease. 2017;4:2054358117703985. 3. kellum ja, lameire n, aspelin p, barsoum rs, burdmann ea, goldstein sl, et al. kidney disease: improving global outcomes (kdigo) acute kidney injury work group. kdigo clinical practice guideline for acute kidney injury. kidney international supplements. 2012;2(1):1138. 4. noritomi dt, soriano fg, kellum ja, cappi sb, biselli pj, liborio ab, et al. metabolic acidosis in patients with severe sepsis and septic shock: a longitudinal quantitative study. critical care medicine. 2009;37(10):2733-9. 5. stewart pa. modern quantitative acid–base chemistry. canadian journal of physiology and pharmacology. 1983;61(12):1444-61. 6. charlson me, pompei p, ales kl, mackenzie cr. a new method of classifying prognostic comorbidity in longitudinal studies: development and validation. journal of chronic diseases. 1987;40(5):373-83. 7. zimmerman je, kramer aa, mcnair ds, malila fm. acute physiology and chronic health evaluation (apache) iv: hospital mortality assessment for today’s critically ill patients. critical care medicine. 2006;34(5):1297-310. 8. levey as, becker c, inker la. glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. jama. 2015;313(8):837-46. 9. hoste ea, bagshaw sm, bellomo r, cely cm, colman r, cruz dn, et al. epidemiology of acute kidney injury in critically ill patients: the multinational aki-epi study. intensive care medicine. 2015;41(8):1411-23. 10. bouchard j, acharya a, cerda j, maccariello er, madarasu rc, tolwani aj, et al. a prospective international multicenter study of aki in the intensive care unit. clinical journal of the american society of nephrology. 2015:cjn. 04360514. 11. toyonaga y, kikura m. hyperchloremic acidosis is associated with acute kidney injury after abdominal surgery. nephrology. 2017;22(9):720-7. 12. bockenkamp b, vyas h. understanding and managing acute fluid and electrolyte disturbances. current paediatrics. 2003;13(7):520-8. 13. relman as, lennon ej, lemann j. endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects. the journal of clinical investigation. 1961;40(9):1621-30. 14. widmer b, gerhardt re, harrington jt, cohen jj. serum electrolyte and acid base composition: the influence of graded degrees of chronic renal failure. archives of internal medicine. 1979;139(10):1099-102. 15. wright g, noiret l, damink swo, jalan r. interorgan ammonia metabolism in liver failure: the basis of current and future therapies. liver international. 2011;31(2):16375. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e48 br i e f re p o rt characteristics of mortalities related to pulmonary embolism following multiple trauma; a brief report fares najari1∗, babak mostafazadeh1, asadollah akbari2, ideh baradaran kayai2, dorsa najari3 1. forensic medicine department, shohadaye tajrish hospital, medical faculty, shahid beheshti university of medical sciences, tehran, iran. 2. legal medicine organization, tehran, iran. 3. medical faculty, shahid beheshti university of medical sciences, tehran, iran. received: march 2018; accepted: may 2018; published online: 7 august 2018 abstract: introduction: pulmonary embolism (pe) is introduced as the third major cause of death after trauma in those who survive more than 24 hours. this study aimed to describe the characteristics of mortalities due to trauma related pe in cases referred to the forensic medicine department. methods: the present cross sectional study was conducted on medical profiles of cadavers that were registered as trauma related mortality in the dissection department of the forensic medicine organization, tehran, iran, during 2011 to 2016. results: the cause of death for 92 of the 10800 (0.85%) evaluated cadavers was diagnosed as trauma related pe. the mean age of these patients was 58.37 ± 19.39 years (66.3% male). only 14 (15.2%) hospitalized patients had received anticoagulant agents. the most frequent trauma related pe mortality cases were male (p = 0.003) and aged > 55 years (p = 0.005), with trauma to death time of < 3 weeks (p = 0.004), lower limb injury (p = 0.003), car crash trauma mechanism (p = 0.003), and no anticoagulant prescribed (p = 0.001). conclusion: according to the results of the present study, the prevalence of trauma related pe mortality was 0.85%. it seems that, having a clear anticoagulation therapy protocol in trauma centers could be helpful in decreasing the prevalence of traumatic thromboembolism and its’ related mortality. keywords: venous thromboembolism; multiple trauma; pulmonary embolism; mortality; forensic medicine © copyright (2018) shahid beheshti university of medical sciences cite this article as: najari f, mostafazadeh b, akbari a, baradaran kaya i, najari d. characteristics of mortalities related to pulmonary embolism following multiple trauma; a brief report. 2018; 6(1): e48. 1. introduction trauma patients are predisposed to venous thromboembolism (vte) and pulmonary embolism (pe). increase in the activity of blood coagulation factors, local vascular injuries in the damaged tissues, and hospitalization are some of the predisposing factors of thrombosis in these patients. so, some traumas may not be fatal in nature but may cause death due to pe (1). pe is introduced as the third major cause of death after trauma in patients who survive more than 24 hours after injury (2). the reported incidence of vte after trauma anges from 7% to 58% depending on the demographics of the patients, the nature of the injuries, the method of detection (i.e. surveillance imaging versus clinical ∗corresponding author: fares najari; forensic medicine department, shohadaye tajrish hospital, tajrish square, tehran, iran. tel: 00989123195140 email: najari.hospital@sbmu.ac.ir. detection), and the type of vte prophylaxis (if any) used in the study population (1-5). vte is asymptomatic, and more than 70% of pe cases go undetected until a postmortem examination is performed after sudden death. sudden death is often the first sign of pe (6). since the mortality rate of post-traumatic pe approaches 50% in some series, most trauma centers have developed protocols for vte prophylaxis, although there are no large studies to document the efficacy of any method of prophylaxis in this heterogeneous population. in a study by mostafazadeh et al. on 200 cadavers suspected of having pe, its prevalence was estimated as 13.5% (7). this study aimed to describe the characteristics of trauma related vte mortality cases referred to the forensic medicine department. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. najari et al. 2 2. methods 2.1. study design and setting the present cross sectional study was conducted on medical profiles of cadavers who were registered as trauma related mortality in the dissection department of the forensic medicine organization, tehran, iran, from 2011 to 2016. the study was approved by the ethics committee of shahid beheshti university of medical sciences; all data were treated as confidential. 2.2. participants cases whose cause of death was diagnosed as trauma related pe at least 48 hours post trauma were enrolled. pe was confirmed based on autopsy and pathology findings or by computed tomography (ct) angiography conducted in the hospital. trauma related pe was define as pe that had started at least forty eight hours after the trauma up to 90 days after the trauma in a healthy patient without any underlying risk factor for thromboembolism. 2.3. data gathering data were gathered from medical profiles and autopsy reports by a trained forensic medicine resident. using a researcher-made data collection form demographic data (age, sex), trauma to death time, site of injury, trauma mechanism, and anticoagulant therapy were gathered for all of trauma related pe mortality cases. 2.4. statistical analysis data were descriptively analyzed using spss version 18 software. qualitative data are reported as frequencies and percentages, and quantitative data as mean ± standard deviation. chi square test was used for analysis and p < 0.05 was considered as the level of significance. 3. results: 10,800 cadavers of patients who had died from trauma were evaluated. the cause of death was diagnosed as trauma related pe for 92 (0.85%) cadavers. the mean age of these patients was 58.37 ± 19.39 (23-89) years (66.3% male). table 1 shows the baseline characteristics of studied cadavers. pe was confirmed based on autopsy findings in 82 (89.1%) cases and via ct angiography in 10 (10.9%) cases. 60 (65.2%) cases had died during hospitalization, and 32 (34.8%) after discharge from hospital and in outpatients setting. none of the discharged patients were prescribed anticoagulant and only 14 (15.2%) hospitalized patients had received anticoagulant agents. the most frequent trauma related pe mortality cases were male (p = 0.003) and aged > 55 table 1: relationship between baseline characteristics of patients and trauma related thromboembolism mortality variables number (%) p sex male 61 (66.3) 0.003 female 31 (33.7) age (year) 23 35 6 (6.5) 35 55 23 (25) 0.004 > 55 63 (68.5) trauma mechanism car crash 64 (69.6) falling 18 (19.6) 0.003 assault 5 (5.4) unknown 5 (5.4) body site of injury lower limb 45(48.9) head 36 (39.1) 0.003 spinal cord 10 (10.9) upper limb 1 (1.1) trauma to death time (day) 2 – 7 13 (14.1) 7 – 14 25 (27.2) 0.004 14 – 21 17 (18.5) > 21 37 (40.2) anticoagulant therapy yes 14 (15.2) 0.001 no 78 (84.8) years (p = 0.005), with trauma to death time of < 3 weeks (p = 0.004), lower limb injury (p = 0.003), car crash trauma mechanism (p = 0.003), and no anticoagulant prescribed (p = 0.001). 4. discussion according to the results of the present study, the prevalence of trauma related pe mortality was 0.85%. in a study by ho et al. in 2009 in perth, west australia, the prevalence of thromboembolism in similar cases was reported as 1.6% (8). in another study by echeverria et al., in sao jose hospital in rio pareto, brazil, from july 2004 to june 2005, the total prevalence of thromboembolism was 2.75% (9). to explain the difference among the reported rates, former studies just focused on inpatients that died from thromboembolism after trauma, whereas the present study also included patients who died in their homes and were assessed in the dissection department of the forensic organization. the mean age of the patients in the present study was 58.4 years, and most of the cases were aged >50 years. in line with our results, in the study by mostafazadeh et al. most of the investigated cases were also aged >50 years (7). some other studies also reported age of >40 years as a risk factor of thromboembolism (2, 4). in addition, a study by alikhan et al. on cadavers that had undergone biopsy between 1991 and 2000 in king’s college hospital, london, uk, showed that the mean age of the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e48 patients who died from pe was 72 years and that 80% of them were aged >60 years (10). the aforementioned results indicated that as age increases, the mortality from thromboembolism after trauma also increases. in a study by ho et al. that was published in the british journal of anaesthesia, a significant association was reported between fatal embolism and old age, accompanying disease, and high body mass index, although no significant association was observed with the place of trauma (8). however, a significant association was observed between lower limb and head injuries, with death from embolism after trauma in the present study. in a study conducted by lu in china from 2003 to 2004 on traumatized patients with lower limb fractures, the prevalence of vte was reported to be 12.4% and femoral shaft fracture was the most common fracture among the studied cases (11). it is noteworthy that patients with head trauma were also at high risk of thromboembolism (12). according to the results of the present study, the maximum time interval between the incidence of trauma and death was less than 3 weeks; however, in a study by yarak et al. in istanbul, turkey, from january 2010 to december 2014, the prevalence of death from pte was 74% within the second week post trauma (13). echeveria et al., in a study from 2004 to 2005, also reported car crash followed by falling from height as the main causes of death among cases who were referred to the forensic medicine organization; the findings were in agreement with those of the present study (9). since approximately 35% of fatal embolism cases occur in outpatients immobilized because of splinting or casting, the application of a pharmaceutical/non-pharmaceutical method at the time of discharge is recommended to prevent thromboembolism in such patients. hence, mechanical or medical prophylaxis, such as clexane, is recommended to prevent thromboembolism in outpatients. 5. conclusion according to the results of the present study, the prevalence of trauma related pe mortality was 0.85%. it seems that, having a clear anticoagulation therapy protocol in trauma centers could be helpful in decreasing the prevalence of traumatic thromboembolism and its related mortality. 6. appendix 6.1. acknowledgements the authors are grateful to the manager and staff of the autopsy hall of tehran medicine organization. 6.2. author contribution all authors met the four criteria for authorship contribution based on the recommendations of the international committee of medical journal editors. 6.3. funding this study did not receive any specific grant from public funding agencies or commercial, or not-for-profit sectors. 6.4. conflict of interest none. references 1. mclaughlin df, wade ce, champion hr, salinas j, holcomb jb. thromboembolic complications following trauma. transfusion. 2009;49(s5):256s-63s. 2. knudson mm, ikossi dg. venous thromboembolism after trauma. curr opin crit care. 2004;10(6):539-48. 3. golin v, sprovieri srs, bedrikow r, salles mjc. pulmonary thromboembolism: retrospective study of necropsies performed over 24 years in a university hospital in brazil. sao paulo medical journal. 2002;120(4):1058. 4. anderson fa, spencer fa. risk factors for venous thromboembolism. circulation. 2003;107(23 suppl 1):i-9-i-16. 5. knudson mm, ikossi dg, khaw l, morabito d, speetzen ls. thromboembolism after trauma: an analysis of 1602 episodes from the american college of surgeons national trauma data bank. annals of surgery. 2004;240(3):490. 6. nutescu ea. assessing, preventing, and treating venous thromboembolism: evidence-based approaches. american journal of health-system pharmacy. 2007;64(11 supplement 7):s5-s13. 7. mostafazadeh b, ahmad efs, zavvareh ht, gharadaghi j, saleki s. prevalence of pulmonary thromboemboli among referred cadavers having hospitalization records to tehran legal medicine center. journal of forensic and legal medicine. 2008;15(5):322-4. 8. ho km, burrell m, rao s, baker r. incidence and risk factors for fatal pulmonary embolism after major trauma: a nested cohort study. british journal of anaesthesia. 2010;105(5):596-602. 9. echeverria rf, baitello al, de godoy jmp, espada pc, morioka ry. prevalence of death due to pulmonary embolism after trauma. lung india: official organ of indian chest society. 2010;27(2):72. 10. alikhan r, peters f, wilmott r, cohen a. fatal pulmonary embolism in hospitalised patients: a necropsy review. journal of clinical pathology. 2004;57(12):1254-7. 11. lu y, ma b, guo r, wang y, zhang j, wu y, et al. deep vein thrombosis in trauma: a prospective study of lower limb this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. najari et al. 4 orthopedic trauma patients in tianjin hospital, china. international angiology. 2007;26(2):165. 12. praeger aj, westbrook aj, nichol ad, wijemunige r, davies ar, lyon sm, et al. deep vein thrombosis and pulmonary embolus in patients with traumatic brain injury: a prospective observational study. critical care and resuscitation. 2012;14(1):10. 13. yakar a, yakar f, ziyade n, yildiz m, uzun i. fatal pulmonary thromboembolism. european review for medical and pharmacological sciences. 2016;20(7):1323-6. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2021; 9(1): e3 https://doi.org/10.22037/aaem.v9i1.928 or i g i n a l re s e a rc h the clinical skills of emergency medical service (ems) personnel regarding spinal immobilization of trauma victims; a cross sectional study nasir jadgal1∗, malahat nikravan mofrad1, maryam jamsahar1, malihe nasiri2 1. department of medical surgical nursing, school of nursing and midwifery, shahid beheshti university of medical sciences, tehran, iran. 2. department of biostatics, shahid beheshti university of medical sciences, tehran, iran. received: october 2020; accepted: october 2020; published online: 10 november 2020 abstract: introduction: spinal immobilization is the most important measure the emergency medical service (ems) has to take when facing the victims of traumatic events, especially those with confirmed or suspected traumatic spinal cord injury (tsci). the aim of this study was to investigate the clinical skills of ems personnel regarding the spinal immobilization of trauma victims. methods: this cross-sectional study was conducted to examine the clinical skills of ems personnel, regarding spinal immobilization of trauma victims during a 1-year period in 2019. ems personnel were selected via convenience sampling method. data collection tools were a demographic questionnaire and a researcher-made checklist to assess clinical skills. the face and content validity of the tool was reviewed and approved by 10 experts. also, the overall reliability coefficient for the skills was 0.98. data were collected by the researcher through observing the skills performed, and filling out the clinical skills checklist accordingly. results: the mean overall score of the clinical skills of the 120 participants regarding spinal immobilization of trauma victims in supine, prone, and sitting positions were 0.60 ± 1.44, 0.58 ± 1.42 and 0.65 ± 1.62, respectively. most of the studied personnel had moderate clinical skills in spinal immobilization, and they had poor clinical skills required to correctly pull the trauma victims in the longitudinal axis of the body to put them on a long backboard and immobilize their torso, legs, and head using the kendrick extrication device (ked). conclusion: the studied ems personnel had moderate clinical skills regarding the spinal immobilization of trauma victims. it is recommended that the ems training programs focus more on the practical aspects of clinical skills in addition to theoretical aspects. keywords: advanced trauma life support care; spinal cord injuries; emergency medical services; clinical competence cite this article as: jadgal n, nikravan mofrad m, jamsahar m, nasiri m. the clinical skills of emergency medical service (ems) personnel regarding spinal immobilization of trauma victims; a cross sectional study. arch acad emerg med. 2021; 9(1): e3. 1. introduction traumatic spinal cord injury (tsci) is a devastating injury resulting from traumatic events, which can affect many functions of the body and can be life-threatening (1). the annual tsci incidence rate varies from 12.7 to 52.2 cases per million populations (2). however, this rate is about 40 to 50 people per million in iran (3). tsci causes lifelong disability in addition to devastating physical injury, tsci can lead to long-term disability and place a heavy social and finan∗corresponding author: nasir jadgal; school of nursing and midwifery, hashemi rafsanjani hwy, tehran, iran. emails: nasirjadgal@sbmu.ac.ir, nasirems7@gmail.com, tel: 982188655366, fax: 982188655366, orcid: http://0000-0002-4785-4746. cial burden on patients, their families and the community (2). despite the introduction of injury prevention programs and advances in vehicle safety systems, such as airbags and seatbelts, tsci still has a profound effect on the healthcare system (4). the emergency medical service (ems) is responsible for providing care and treatment services to trauma victims at the scene of the accident and during transportation to the hospital (5). spinal immobilization is the most important measure that the ems should take when facing victims of traumatic events, especially for those with confirmed or suspected tsci (6). in the united states, more than 5 million patients per year are immobilized, mostly with a cervical collar and a backboard (7). ems personnel use spinal immobilization on the field to maintain the normal anatomical alignment and restrict the motion of the spinal cord (8). the inthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. jadgal et al. 2 tent behind spinal immobilization is to reduce spinal movement and prevent further secondary injury, prevent nervous system deterioration, and facilitate the movement and transfer of a patient (9). it is estimated that 3 to 25% of tscis are secondary, which occur after a primary injury, due to inappropriate management at the scene of the accident or during transport to the hospital (10). therefore, it is very important to start tsci-related measures and care from the scene of the accident (4). providing high-quality, timely, and standard services for victims and emergency patients in the early moments of traumatic events can reduce mortality and increase patients’ trust in and satisfaction with ems (11). assessing the clinical skills of ems personnel may provide an appropriate reflection of the training programs. a number of studies have been conducted to examine the clinical skills of ems personnel regarding spinal immobilization of the injured persons lying in the supine position (12-14); however, no studies have been conducted on the victims lying in prone position. therefore, the aim of this study was to evaluate the clinical skills of ems personnel regarding spinal immobilization of trauma victims lying in supine position, lying in prone position, and placed in the sitting position. 2. methods 2.1. study design and setting this cross-sectional study was conducted to examine the clinical skills of ems personnel of iranshahr university of medical sciences, iranshahr, iran, regarding spinal immobilization of trauma victims during a 1-year period in 2019. sampling was performed in 43 emergency stations located in five cities of iranshahr, chabahar, konarak, rask, and qasr ghand. the clinical skills of ems personnel regarding spinal immobilization of victims of traumatic events were assessed using a researcher-made questionnaire checklist. the study protocol was approved by the ethics committee of shahid beheshti university of medical sciences with the id: ir.sbmu.pharmacy.rec.1398.262. 2.2. the study participants the study population consisted of all ems personnel working in iranshahr university of medical sciences, iranshahr, iran, 120 of whom were selected using convenience sampling based on the sample size formula. having a high school diploma, nursing assistant certificate, associate degree or bachelor’s degree in nursing, medical emergencies, or operating room and experience of working in the pre-hospital emergency unit were among the inclusion criteria. personnel working in the administrative unit of pre-hospital emergency or the dispatch unit were excluded from the study. table 1: the baseline characteristics of the participants variable number (%) age (year) 20-30 65 (54.2) 31-40 48 (40.0) ≥ 40 7 (5.8) field of study pre-hospital emergency 69 (58.5) operating room 5 (5.0) others* 45 (37.5) level of education high school diploma 45 (37.5) associate’s degree 67 (55.8) bachelor’s degree 8 (6.7) place for ems work urban station 37(30.8) on roads station 83(69.2) work experience(year) 0-10 101 (84.2) 11-20 18 (15.0) ≥ 20 1 (0.8) type of employment under –a-contract 41 (34.2) temporary 18 (15) casual 5 (4.2) contractual 28 (23.3) temporary to official 22 (18.3) official 6 (5.0) participation in training program yes 47 (39.2) no 73 (60.8) *a high school diploma in natural sciences or a nursing assistant certificate. data are presented as frequency (%). 2.3. data collection the data were collected using a demographic questionnaire and a clinical skills checklist consisting of the three checklists used for the assessment of the clinical skills of ems personnel regarding spinal immobilization of trauma victims in three positions: supine, prone and sitting. for the face and content validity, the tool was evaluated by 10 experts. the reliability of the tool for overall clinical skills was 0.98. the participants’ demographic characteristics such as age, level of education, field of study, type of employment, work experience, place for ems work, and history of participation in a training program for the spinal immobilization over the last year were assessed. the data were collected by a senior nursing expert. in order to collect data, the researcher referred to the ems of iranshahr university of medical sciences, iranshahr, iran, after coordination with the relevant authorities. he guaranteed the participants confidentiality after explaining the study purpose to them. the clinical skills of ems personnel were assessed by the researcher in the ems stations. written informed consent was obtained from the participants. for this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e3 table 2: mean scores of clinical skills for studied ems personnel regarding spinal immobilization of trauma victims lying in supine position clinical skills score mean± sd 2 1 0 separation of body secretions 62.5 25.0 12.5 1.50 ± 0.71 keeping head in a neutral position with hands 73.3 18.3 8.3 1.65 ± 0.63 picking the correct cervical collar 55.8 31.7 12.5 1.43 ± 0.70 applying cervical collar 83.3 13.3 3.3 1.80 ± 0.47 placement of the long backboard next to the victim 19.2 80.0 0.8 1.18 ± 0.40 transfer of the injured person on the long backboard 45 53.3 1.7 1.43 ± 0.53 pulling the injured person in the longitudinal axis of the body to put him/her on a long backboard 14.2 77.5 8.3 1.05 ± 0.47 the use of head immobilizers 60.8 20.8 18.3 1.42 ± 0.78 immobilizing head on a long backboard using straps 44.2 35.8 20.0 1.24 ± 0.76 immobilizing arms and legs on a long backboard using straps 81.7 10.0 8.3 1.73 ± 0.60 sd: standard deviation. the data are expressed as percentage for each score. * score 2 if correct, 1 if incorrect, and 0 for not performing the clinical skill. table 3: mean scores of clinical skills for studied ems personnel regarding spinal immobilization of trauma victims lying in prone position clinical skills score mean± sd 2 1 0 separation of body secretions 63.3 24.2 12.5 1.50 ± 0.71 keeping head in a neutral position by hands 63.3 30.8 5.8 1.57 ± 0.60 picking the correct cervical collar 20.0 80.0 0.0 1.20 ± 0.40 applying cervical collar 23.3 76.7 0.0 1.23 ± 0.42 placement of the long backboard next to victim 15.0 77.5 7.5 1.07 ± 0.47 transfer of the injured person on the long backboard 62.5 26.7 10.8 1.51 ± 0.68 pulling the injured person in the longitudinal axis of the body to put him/her on a long backboard 74.2 24.2 1.7 1.72 ± 0.48 the use of head immobilizers 61.7 22.5 18.8 1.45 ± 0.75 immobilizing head on a long backboard using straps 43.3 40 16.7 1.26 ± 0.73 immobilizing arms and legs on a long backboard using straps 80.8 10.8 8.3 1.72 ± 0.60 sd: standard deviation. the data are expressed as percentage for each score. *score 2 if correct, 1 if incorrect, and 0 for not performing the clinical skill. table 4: mean scores of clinical skills for studied ems personnel regarding spinal immobilization of trauma victims lying in prone position clinical skills score mean± sd 2 1 0 separation of body secretions 63.3 25.0 11.7 1.51 ± 0.69 keeping head in a neutral position by hands 74.2 14.2 11.7 1.62 ± 0.68 picking the correct cervical collar 63.3 27.5 9.2 1.54 ± 0.65 applying cervical collar 80 19.2 0.8 1.79 ± 0.42 placement of ked in the back of the injured person 53.3 45.8 0.8 1.52 ± 0.51 tightening the straps of torso, legs and head using the ked 20.8 75.0 4.2 1.16 ± 0.47 transfer of the injured person on the long backboard 40.0 57.5 2.5 1.37 ± 0.53 pulling the injured person in the longitudinal axis of the body to put him/her on a long backboard 40.8 56.7 2.5 1.38 ± 0.53 the use of head immobilizers 61.7 21.7 16.7 1.45 ± 0.76 immobilizing head on a long backboard using straps 40.8 40.8 18.3 1.22 ± 0.73 immobilizing arms and legs on a long backboard using straps 81.7 9.2 9.2 1.72 ± 0.65 sd: standard deviation. the data are expressed as percentage for each score. *score 2 if correct, 1 if incorrect, and 0 for not performing the clinical skill. ked: kendrick extrication device. this purpose, first, the demographic questionnaire was given to the participants and then they were asked to use the clinical skills for the simulated patient in supine, prone, and sitting positions, in order to assess their clinical skills regarding spinal immobilization. the researcher recorded the scores of each skill in the clinical skill checklist. in this study, the simulated patient was 32 years old, weighing 73 kg. the clinical skills of each member of ems personnel were assessed separately without the presence of others. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. jadgal et al. 4 table 5: the relationship between the clinical skills regarding spinal immobilization and the demographic characteristics of the studied participants variables mean± sd p age (year) 20-30 44.56 ± 8.22 31-40 46.70 ± 6.05 0.02 ≥ 40 38.42 ±10.98 field of study pre-hospital emergency technician 46.59 ± 6.03 operating room 38.00 ± 13.84 0.01 others* 43.66 ± 8.59 level of education high school diploma 43.66 ± 8.59 associate’s degree 45.52 ± 7.38 0.15 bachelor’s degree 49.12 ± 4.54 place for ems work urban station 47.29 ± 7.86 0.03 on roads station 44.07 ± 7.59 work experience (year) 0-10 45.63 ± 7.33 0.11 11-20 41.61 ± 9.61 type of employment under -a-contract 45.17 ± 7.35 temporary 45.61 ± 8.08 casual 32.20 ± 9.12 0.00 contractual 44.67 ± 8.58 temporary to official 47.00 ± 5.03 official 48.16 ± 4.95 participation in training program yes 48.27 ± 53.5 0.00 no 43.00 ± 8.35 *a high school diploma in natural sciences or a nursing assistant certificate. data are presented as mean ± standard deviation. 2.4. instruments after the simulated patient was put in the supine, prone, and sitting positions, the participants were asked to use the spinal immobilization based on the clinical skill checklist. the researcher recorded the scores of each skill in the corresponding checklist. the clinical skill checklist of the spinal immobilization in supine position contained 10 items or practical steps. the clinical skill checklist of the spinal immobilization in prone position contained 10 items or practical steps. the clinical skill checklist of the spinal immobilization in sitting position contained 11 items or practical steps. each item or every step is scored on a 0 to 2 scale (2 if correct, 1 if incorrect, and 0 for not performing the clinical skill). the level of clinical skills was also evaluated as follows: 1.7-2 = good; 1.2-1.7 = moderate; lower than 1.2 = poor. 2.5. statistical analysis all statistical analyses were performed using spss version 21. mean ± standard deviation (sd) or frequency (%) was used to report the results. analysis of variance (anova) was used to examine the relationship between the clinical skills regarding spinal immobilization and demographic characteristics of the participants. p-value less than 0.05 was considered statistically significant. 3. results 3.1. the demographic characteristics of the participants the mean age of the participants (n=120) was 6.14 ± 30.3 years (100% male). the demographic characteristics of the participants are shown in table 1. 54.2% of the participants were in the 20–30 years age group. 69 (57.5%) had a degree in pre-hospital emergency care and 67 (55.8%) had an associate degree. the majority of the participants (69.2%) provided care on the roads station. 101 subjects (84.2%) had a work experience of 0–10 years. 73 participants (60.8%) did not participate in the training program for spinal immobilization over the last year. 3.2. the clinical skills of the participants regarding spinal immobilization the mean overall score of the clinical skills of the participants regarding spinal immobilization of trauma victims in supine, prone, and sitting positions were 0.60 ± 1.44, 0.58 ± 1.42, and 0.65 ± 1.62, respectively (tables 2, 3, and 4). a significant difference was observed between the participants’ scores based on their field of study (p = 0.01), place for ems work (p = 0.03), type of employment (p = 0.00), and history of participation in the training program for spinal immobilization over the last year (p < 0.0001) (table 5). 3.3. discussion the results of the present study showed that the participants had moderate clinical skills regarding spinal immobilization. regarding clinical skills of the participants in spinal immobilization of trauma victims lying in supine position, our findings showed that the highest score belonged to the use of cervical collar in the victims and the majority of participants applied it correctly, but they had poor clinical skills regarding pulling the trauma victims in the longitudinal axis of the body to put them on a long backboard and immobilize their torso, legs and head using the kendrick extrication device (ked) and most of them applied it incorrectly. in 2018, azimi et al. showed that the majority of nurses had moderate clinical skills regarding spinal immobilization of the injured persons in traffic accidents, and they also had poor clinical skills regarding the injured person’s correct transfer to the long back board using the log roll technique and fixing arms and legs on the long backboard (12), which were consistent with our results. correct transfer of the injured person from this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e3 the accident scene to the long backboard is a key step in implementing spinal immobilization of trauma victims, which requires precision, ability, and coordination of ems personnel to immobilize the spine in the longitudinal axis of the body, all parts of the injured body should be slowly transferred to the backboard. kumar et al. in 2008 examined the level of knowledge, attitude, and practice of three groups of health care providers about prehospital and emergency care. they reported that the level of knowledge and practice of participants regarding emergency and prehospital care was below average, and therefore ongoing training was required in this area (15). regarding clinical skills of the participants on spinal immobilization of trauma victims lying in prone position, our findings demonstrated that the majority of participants used cervical collar in the victims correctly. also, most of them had correctly fixed arms and legs on the long backboard using straps, but they had poor clinical skills regarding pulling the trauma victims in the longitudinal axis of the body to put them on a long backboard. the total score in this skill was in the moderate level, which was not satisfactory. in 2016, norouzinia et al., assessed the level of knowledge and clinical skills of pre-hospital emergency care students confronting trauma victims in their study, and the results showed that 89.1% of the participants had good clinical skills for confronting trauma victims in pre-hospital setting (13). however, the results of the study by dadashzadeh et al. in 2017 showed that despite the large number of persons with head and neck injuries, the cervical collar and long backboard has been merely used for the immobilization of a few traumatic patients, which requires further investigation and trauma management training programs for ems personnel (5). also, the results of mohseni et al.’s study in 2014 showed that the use of long backboard (12.2%) and cervical collar (15.6%) in the patients was the neurological care least provided by ems personnel for trauma victims, which was not performed despite the necessity (16). the differences between the results of studies can be attributed to the differences in level of education and training for the ems personnel because graduates of various fields of study such as nursing, pre-hospital emergency, operating room, nursing assistance, and even people with a high school diploma who were trained in this regard have been employed in the ems setting. regarding clinical skills of the participants in spinal immobilization of trauma victims placed in the sitting position, our results demonstrated that the participants had moderate clinical skills in this regard, but most of them had poor clinical skills regarding immobilizing the torso, legs and head using the ked. given that spinal immobilization can be performed by tightening the straps of torso, legs and head using the ked, more attention should be paid to the performance of this skill and training in this regard. shakeri et al., in their study in 2012, evaluated clinical skills of medical emergency personnel in tehran emergency center in confronting trauma and the results showed that 62.4% of the medical emergency personnel had good grades in trauma skill but had major skill deficiency in practicing two skills, namely seated patient’s spinal immobilization and traction splint, because these skills were less commonly used in the ems setting (14), which were consistent with our results. also, the study by dunn et al. in 2004 examined the ability of basic emergency technicians in using the protocol of selective immobilization of cervical spine in trauma patients and compared it with the performance of the paramedics. they showed that this skill is the same in both groups, and by providing the correct training, the clinical skills of basic emergency technicians can be improved (17). the repetition of clinical skills during standard training programs is the most important factor in improving the clinical skill level of ems personnel (18). in this study, the lack of a clinical skill center and the lack of proper access to them were considered as important obstacles for the participants to achieve good clinical skills. 4. limitation fatigue among participants due to working 24-hour shifts and their specific job conditions, as well as the personal problems of the participants during the implementation of the clinical skills might have affected the results, all of which were beyond the control of the researcher. however, by conducting this study in appropriate conditions, in the ems stations, an attempt was made to reduce their impact on the results. additionally, observing the staff when implementing spinal immobilization skills might have influenced their performance. 5. conclusion the ems personnel had moderate clinical skills regarding spinal immobilization of trauma victims, and they had poor clinical skills regarding pulling the trauma victims in the longitudinal axis of the body to put them on a long backboard and immobilizing their torso, legs and head using ked for the sitting patient. it is recommended that the ems training programs focus more on the practical aspects of clinical skills in addition to training theoretical aspects. 6. declarations: 6.1. acknowledgements we would like to express our deep gratitude and appreciation to personnel working in ems in chabahar and other prehospital emergency centers affiliated to iranshahr university of medical sciences, iranshahr, iran. we would also like to this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem n. jadgal et al. 6 thank student research committee and the deputy for research and technology of shahid beheshti university of medical sciences that provided financial support for this study. 6.2. author contribution all authors met the four criteria for authorship based on guidelines of the international committee of medical journal publishers. 6.3. funding/support none. 6.4. conflict of interest none. references 1. hasanzadeh pashang s, zare h, alipor a. the efficacy of stress inculation training (sit) on resilience, anxiety, depression and stress among spinal cord injury (sci) patients. pars journal of medical sciences ( jahrom medical journal). 2012;10(3):12-20. 2. oteir ao, smith k, jennings pa, stoelwinder ju. the prehospital management of suspected spinal cord injury: an update. prehosp disaster med. 2014;29(4):399-402. 3. khazaeli k, hoseini e, nasir ah, amarloui m, ganji mk. relationship between level of injury and quality of life in spinal cord injury (sci) patients. payesh. 2019;18(1):4551. 4. shank cd, walters bc, hadley mn. current topics in the management of acute traumatic spinal cord injury. neurocritical care. 2019;30(2):261-71. 5. dadashzadeh a, dehghannejhad j, shams vahdati s, soheili a, sadeghi bazarghani h. the nature of prehospital medical interventions delivered to traumatic patients in tabriz. journal of urmia nursing and midwifery faculty. 2017;15(3):159-67. 6. ahuja cs, wilson jr, nori s, kotter mr, druschel c, curt a, et al. traumatic spinal cord injury. nature reviews disease primers. 2017;3(1):1-21. 7. ten brinke jg, gebbink wk, pallada l, saltzherr tp, hogervorst m, goslings jc. value of prehospital assessment of spine fracture by paramedics. european journal of trauma and emergency surgery : official publication of the european trauma society. 2018;44(4):551-4. 8. feller r, furin m, reynolds c. ems, immobilization (seated and supine). statpearls [internet]. treasure island (fl): statpearls publishing; 2019. 9. oteir ao, jennings pa, smith k, stoelwinder j. should suspected cervical spinal cord injuries be immobilised? a systematic review protocol. injury prevention : journal of the international society for child and adolescent injury prevention. 2014;20(3):e5. 10. theodore n, hadley mn, aarabi b, dhall ss, gelb de, hurlbert rj, et al. prehospital cervical spinal immobilization after trauma. neurosurgery. 2013;72(3):22-34. 11. bayrami r, ebrahimipour h, hasanzadeh a. challenges in pre hospital emergency medical service in mashhad: a qualitative study. hospital. 2017;16(2 (61)). 12. azimi m, khankeh h, biglaryan a, sedghi n. assessment of restrictions on movement skills spinal injury patients due to traffic accidents in tehran nurses emergency operations. journal of nursing education. 2018;7(3):8-13. 13. norouzinia r, ahmadi m, seidabadi m. knowledge and clinical competence of medical emergencies students in facing trauma. iranian journal of emergency medicine. 2016;3(2):73-7. 14. shakeri k, fallahi khoshknab m, khankeh h, hosseini m, hosseinzadeh s, haghi monie n. evaluation of clinical skills of medical emergency personnel in tehran emergency center confronting the trauma. journal of health promotion management. 2012;1(4):16-24. 15. kumar s, agarwal ak, kumar a, agrawal gg, chaudhary s, dwivedi v. a study of knowledge, attitude and practice of hospital consultants, resident doctors and private practitioners with regard to pre-hospital and emergency care in lucknow. the indian journal of surgery. 2008;70(1):14-8. 16. mohseni m, khaleghdoost mohammadi t, adib m, mohtasham amiri z, yosefzadeh sh kl. situation of prehospital emergency neurological care and related factors in traumatic patients. journal of health and care. 2014;16(1):55-65. 17. dunn tm, dalton a, dorfman t, dunn ww. are emergency medical technician–basics able to use a selective immobilization of the cervical spine protocol?: a preliminary report. prehospital emergency care. 2004;8(2):20711. 18. kashani p, manouchehrifar m, sohrabi p. evaluating the knowledge and practice of prehospital emergency medical technicians regarding advanced cardiac life support; a cross-sectional study. iranian journal of emergency medicine. 2019;6(1):10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results limitation conclusion declarations: references emergency. 2018; 6 (1): e36 or i g i n a l re s e a rc h awareness of basic life support among egyptian medical students; a cross-sectional study esraa ghanem1,2, muhammad elgazar1, khaled oweda1, hussein tarek1, fathy assaf1, mostafa wanees ahmed el-husseny3, ahmed elgebaly1, abdelrahman ibrahim abushouk2,4∗ 1. faculty of medicine al-azhar university, cairo, egypt. 2. cross sectional research group of egypt, cairo, egypt. 3. faculty of medicine, fayoum university, fayoum, egypt. 4. faculty of medicine, ain shams university, cairo, egypt. received: apri 2018; accepted: june 2018; published online: 16 june 2018 abstract: introduction: it is important for all medical and paramedical staff to be aware of basic life support (bls) maneuvers. in this study, we aimed to evaluate the level of bls awareness among egyptian medical students. methods: the level of bls knowledge was assessed using a validated questionnaire and the results were analyzed using an answer key, prepared from the advanced cardiac life support (acls) manual. we used the student’s t-test to analyze the association between awareness level and year of study, previous bls training and practical experience. results: a total of 823 medical students with the mean age of 20.3 ± 2.7 years, from al-azhar medical schools completed the questionnaire (463 and 360 in academic and clinical years, respectively). about 72% and 84% of students failed to recognize the proper point of chest compression in adults and infants, respectively. moreover, the majority (80%) did not know how to give rescue breathing in infants. only 18% of students correctly identified early signs of shock and only 22% knew how to help patients with myocardial infarction. being in clinical years, previous bls training or practical experience were significantly associated with higher bls knowledge scores (p < 0.001). conclusion: the level of bls awareness among egyptian medical students is generally poor. introduction of regular bls courses into the undergraduate curriculum is a must to increase the level of bls knowledge among egyptian future physicians. keywords: awareness; cardiopulmonary resuscitation; education, medical; students, medical © copyright (2018) shahid beheshti university of medical sciences cite this article as: ghanemi e, elgazar m, oweda kh, tarek h, assaf f, wanees ahmed el-husseny m, elgebaly a, ibrahim abushouk a. awareness of basic life support among egyptian medical students; a cross-sectional study. emergency. 2018; 6(1): e36. 1. introduction c ardiac arrest is a life-threatening event that accounts for 15% of the global mortality and is more common in individuals with a pre-existing cardiovascular condition (1)(2). in egypt, it is estimated that hypertension and coronary heart disease affect 25% and 8.5% of the population, respectively (3), increasing the liability to sudden cardiac arrest events. the emergency management of cardiac arrest involves a series of simple maneuvers, known as ba∗corresponding author: abdelrahman ibrahim abushouk; faculty of medicine, ain shams university, 11566, ramsis st, abbasia, cairo, egypt. tel: 0201014295781, fax: 020132706152 email: abdelrahman.abushouk@med.asu.edu.eg sic life support (bls) (4). these maneuvers include recognizing the signs of sudden cardiac arrest, heart attack, stroke and foreign-body airway obstruction, cardiopulmonary resuscitation (cpr), and defibrillation with an automated external defibrillator (aed) (5,6). the simple skills, a trained bls provider should have, can reduce the high mortality rate associated with cardiac arrest in patients with cardiovascular disease. moreover, cardio-respiratory arrest can also be seen in neonates and infants (7), with slight differences in the bls algorithm that healthcare providers should be aware of. therefore, each individual in the community, specially the medical staff, should have adequate knowledge and training in providing bls maneuvers (5). several studies have assessed the levels of bls awareness among medical students in different countries (5âăş8). however, similar data this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. ghanem et al. 2 on egyptian medical students are lacking. therefore, we performed this cross-sectional study to assess bls awareness among medical students in two large egyptian medical schools. 2. methods 2.1. study design and setting we conducted a cross-sectional study at al-azhar university, cairo, egypt. we obtained verbal consent from all participants after explaining the study objective and the voluntary nature of the questionnaire. the confidentiality of obtained data was maintained according to the helsinki declaration of bioethics (as revised in 2008).we followed the strengthening the reporting of observational studies in epidemiology (strobe) statement guidelines during the preparation of this cross-sectional study (9). 2.2. participants all officially-enrolled undergraduate medical students at alazhar university (including two medical schools) were eligible for participation. the educational model in most egyptian medical schools is similar where students study basic medical (preclinical) sciences during the first three years and applied (clinical) sciences during the final three years. we used the convenience sampling method for enrolling participants, actively attending university courses. 2.3. study questionnaire and data collection we used a validated, closed ended, self-administrated questionnaire with 20 questions about bls maneuvers (assessment of airway, breathing, circulation in unresponsive victims, recognition of early signs of shock, cpr technique, and aed use). this questionnaire was developed by referring to previous studies (5–8). later, we added a section about the demographic data of enrolled students to our survey and another question to determine whether students had attended bls training courses before. a pilot study on 50 students was conducted to test the comprehensibility of the questions and time needed for completion. we used an online survey program (google documents) to enter the data. 2.4. data analysis for calculation of sample size, we used raosoft software (based on the number of students in both schools, a combined sample size of 682 students was sufficient to provide a power of 90% for this study). questionnaire forms with more than two missing elements were removed from the analysis. analysis of the results was performed, using spss (statistical package for social sciences) software (version 20 for windows). results were analyzed using an answer key, prepared from the advanced cardiac life support manual. numerical table 1: baseline and demographic data of participating medical students variable total (n=823) age (years) (mean ± sd) 20.3 ± 2.7 sex male 727 (88.3%) female 96 (11.7%) year of enrollment academic 463 (56.3%) clinical 360 (43.7%) cumulative academic score excellent 227 (27.6%) very good 314 (38.2%) good 187 (22.7%) pass/poor 29 (3.50%) residency area rural 522 (63.4%) urban 301 (36.6%) data are presented as frequencies and percentages unless stated otherwise. figure 1: flow diagram of sampling and analysis processes. variables were reported as means and standard deviations, while categorical variables were reported as frequencies and percentages. the student’s t-test was used to analyze the association between awareness level and year of study, previous bls training or practical experience. 3. results 3.1. basic data of enrolled students a total of 823 students completed the survey (figure 1), including 727 males (88.3%) and 96 females (11.7%). among participating students, 463 students (56.3%) were enrolled in the academic study years, while 360 students (43.7%) were this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e36 in the clinical study years (mean age: 20.3 ± 2.7 years). table 1 summarizes the baseline characteristics of participating medical students in this study. 3.2. students’ knowledge about basic life support among all included students, only 222 students (27%) reported previous attendance of bls courses, while 282 (34.3%) stated that they had attended an external medical/paramedical course before. the correct meaning of the abbreviation “bls” was only identified by 364 (44.8%) students. only 254 responders (30.9%) could select ‘look for safety’ when asked about the first thing to do when you find an unresponsive person in the middle of the road. moreover, only 78 students (9.5%) could identify “activate ems” as the immediate response after confirming the unresponsiveness of that person. the detailed responses to bls knowledge questions are illustrated in table 2. 3.3. association between baseline characteristics and overall score we detected a statistically significant association between sex and the overall score (p < 0.001), with females achieving significantly higher scores than males. no statistically significant association (p = 0.07) was found between the overall score and place of residence (rural/urban). as expected, medical students in the later clinical years achieved significantly higher scores than those in the three academic years (p < 0.001). moreover, a statistically significant association was found between the overall score and previous attendance of bls courses (p < 0.001) or undergoing medical/paramedical training (p < 0.001). 4. discussion our study showed a significant lack of bls knowledge among the enrolled participants. although nearly 60% of the responders reported previous attendance of bls courses, more than 50% of them could not even identify what the abbreviation "bls" stands for. moreover, around 90% of them could not identify ’activate ems’ as the first step in the chain of survival, which is important to get advanced medical care in the exact time. what is more concerning is that two-thirds of the students did not recognize "look for safety" as the first thing to do upon finding an unresponsive patient, which could endanger the lives of both the victim and the rescuer. knowing the proper location, rate, and depth of compressions is also important (10). chest compression at the proper site ensures adequate blood pumping to the circulation to maintain brain perfusion. however, more than 70% of our participants could not identify the correct site of chest compression in adults and 80% could not do the same in infants. moreover, less than 15% could identify the right depth of chest compression in adults, children, and neonates, which makes cpr useless or even harmful. less than 10% of our participants could identify the correct ratio of compression-ventilation in adults or neonates. in case of suspecting an airway obstruction, the first step to confirm that is by talking to the victim. more than 85% of the participants could not identify this step. moreover, only 25% of the students could identify the correct technique of foreign body removal in a choking infant. in case of acute coronary syndrome and stroke, there is a limited period in which the early signs of vascular occlusion should be recognized before the ischemic damage becomes irreversible. however, only 20% of enrolled students could identify those signs in both cases of stroke and acute coronary syndrome. following cardiac arrest, time equals life. for every minute post-cardiac arrest with no resuscitation, there is a decrease in survival rate by 7 to 10% (11). a survival rate of 50 to 75% is possible if cpr and defibrillation are performed within 3 to 5 minutes of cardiac arrest (12,13). it is expected from the practicing physicians to have good bls skills because they face cases of cardiac arrest daily in their hospitals (14). in case of out-of-hospital cardiac arrest, there is an essential role for the bystanders to provide the initial care, which itself may be enough for survival (15) or until experienced medical staff get in place. a major role of spreading the knowledge of bls skills is on the medical students, especially in developing communities (16). similar studies have shown poor bls knowledge levels in different countries (5–8), highlighting the importance of a global consensus among medical educators to enhance bls training of undergraduate students. according to a recent study in scandinavia, following bls training, there was an increased knowledge of bls skills among participating students with reduced time needed to establish cpr in out-of-hospital cardiac arrest situations (8). 4.1. strength points versus limitations of this study according to our knowledge, our study is the first to assess the knowledge about bls in egypt. being a multicenter study, its results can be generalized to a wide population of egyptian medical students. however, we did not assess bls practical skills among our respondents. this should be the focus of future studies. similar surveys should be conducted not only among the medical students, but also among the general population for the purpose of creating numerous bls rapid responders in the community. our results also highlight the need for regular reassessment and refreshing courses for those who already got involved in previous bls courses. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com e. ghanem et al. 4 table 2: detailed responses to bls knowledge questions among participating medical students n question correct answer frequency (%) 1 what is the abbreviation of “bls”? basic life support 364 (44.2) 2 when you find someone unresponsive in the middle of the road, what will be your first response? (note: you are alone there) look for safety 254 (30.9) 3 if you confirm somebody is not responding to you even after shaking and shouting at him, what will be your immediate action? activate ems 78 (9.5) 4 what is the location for chest compression? mid chest 228 (27.7) 5 what is the location for chest compression in infants? one finger breadth above the nipple line 129 (15.7) 6 if you do not want to give mouth-to-mouth cpr, the following can be done except no cpr 139 (16.9) 7 how do you give rescue breathing in infants? mouth-to-mouth and nose 162 (19.7) 8 depth of compression in children during cpr 1 –1 1/2 inches 103 (12.5) 9 depth of compression in adults during cpr one-half to one-third depth of chest 78 (9.5) 10 depth of compression in neonates during cpr one-half to one-third depth of chest 110 (13.4) 11 rate of chest compression in adults and children during cpr 100/min 72 (8.7) 12 ratio of cpr, single rescuer in adults is 30:2 136 (16.5) 13 in a new born the chest compression and ventilation ratio is 3:1 87 (10.6) 14 what does abbreviation aed stands for? automated external defibrillator 63 (7.7) 15 what does abbreviation ems stands for? emergency medical service 178 (21.6) 16 if you and your friend are having food in a canteen and suddenly your friend starts expressing symptoms of choking, what will be your first response? confirm foreign body aspiration by talking to him 115 (14) 17 you are witnessing an infant who suddenly started choking while he was playing with the toy, you have confirmed that he is unable to cry (or) cough, what will be your first response? back blows and chest compression of five cycles each then open the mouth and remove foreign body only when it is seen 225 (27.3) 18 you are witnessing an adult unresponsive victim who has been submerged in fresh water and just removed from it. he has spontaneous breathing, but he is unresponsive. what is the first step? keep him in recovery position 102 (12.4) 19 you noticed that your colleague has suddenly developed slurring of speech and weakness of right upper limb. which one of the following can be done? possibly stroke, he may require thrombolysis and hence activate emergency medical services 151 (18.3) 20 a 50-year-old gentleman with retrosternal chest discomfort, profuse sweating and vomiting. what is next? probably myocardial infarction, hence activates ems, give an aspirin tablet and allow him to rest 180 (21.9) abbreviations: aed: automated external defibrillator, bls: basic life support, cpr: cardiopulmonary resuscitation, ems: emergency medical service. 5. conclusion our study showed a poor level of knowledge about bls skills among egyptian medical students. introduction of regular bls courses into the undergraduate curriculum is a must to increase the level of knowledge about bls among our future physicians and improve awareness of the general population of these life-saving skills. 6. appendix 6.1. acknowledgements none. 6.2. author contribution all authors made substantial contributions, revised the manuscript, and approved the final version for publication. ghanem e, elgazar m, oweda k: conception and design of the study. tarek h, assaf f, elgebaly a: data collection and analysis. el-husseny mwa and abushouk ai: first draft writing and preparing illustrations. 6.3. funding sources none. 6.4. conflict of interest none to declare. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e36 references 1. bogle bm, ning h, mehrotra s, goldberger jj, lloydjones dm. lifetime risk for sudden cardiac death in the community. journal of the american heart association. 2016;5(7):e002398. 2. pundalika d, narayan r, biradar s v, reddy mt, bk s. assessment of knowledge and attitude about basic life support among dental interns and postgraduate students in bangalore city , india. world journal of emergency medicine. 2015;6(2):118–22. 3. kurdi mi. coronary artery disease in africa and the middle east. therapy and clinical risk management. 2012;8:65–72. 4. tipa ro, bobirnac g. importance of basic life support training for first and second year medical students a personal statement-. journal of medicine and life. 2010;3(4):465–7. 5. qassim a. basic life support knowledge of healthcare students and professionals in the qassim university. international journal of health sciences. 2014;8(2). 6. chandrasekaran s, kumar s, bhat sa, shabbir pm, chandrasekaran vp. awareness of basic life support among medical , dental , nursing students and doctors. indian journal of anesthesia. 2010;54(2):121–6. 7. zaheer h, haque z. students’ corner awareness about bls ( cpr ) among medical students: status and requirements. jpma. the journal of the pakistan medical association. 2009;59(1):57–9. 8. meissner tm, kloppe c, hanefeld c. basic life support skills of high school students before and after cardiopulmonary resuscitation training: a longitudinal investigation. scandinavian journal of trauma, resuscitation and emergency medicine. 2012;20(1):31. 9. elm e von, altman dg, egger m, pocock sj, gotzsche pc, vandenbroucke jp, et al. the strengthening the reporting of observational studies in epidemiology ( strobe ) statement: guidelines for reporting observational studies*. international journal of surgery. elsevier ltd; 2014;12(12):1495–9. 10. holmberg m, holmberg s, herlitz j, ga b. survival after cardiac arrest outside hospital in sweden. resuscitation. 1998;36(1):29–36. 11. valenzuela td, roe dj, cretin s, spaite dw, larsen mp. estimating effectiveness of cardiac arrest interventions. circulation. 1997 nov;96(10):3308 lp – 3313. 12. assembiy s, physicians em, auble te, menegazzi jj, paris pm. effect of out-of-hospital defibrillation by basic life support providers on cardiac arrest mortality: a metaanalysis. annals of emergency medicine. 1995;25(5):642– 8. 13. weaver wd, hill d, fahrenbruch ce, copass mk, martin js, cobb la, et al. use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. new england journal of medicine. massachusetts medical society; 1988 sep;319(11):661–6. 14. buck-barrett i, squire i. the use of basic life support skills by hospital staff; what skills should be taught? resuscitation. 2004;60(1):39–44. 15. andreas p, kramer-johansen j. improving cardiopulmonary resuscitation quality to ensure survival. current opinion in critical care. 2008;14(3):299–304. 16. toner p, connolly m, laverty l, mcgrath p, connolly d, mccluskey dr. teaching basic life support to school children using medical students and teachers in a “peertraining” model — results of the “abc for life” programme. resuscitation. 2007;75(1):169–75. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion conclusion appendix references emergency. 2018; 6 (1): e39 br i e f re p o rt candidemia in febrile neutropenic patients; a brief report maysam yousefi1,2, davood yadegarynia1, ensieh lotfali1,3∗ zahra arab-mazar1, ali ghajari3, alireza fatemi1 1. infectious diseases and tropical medicine research center, shahid beheshti university of medial sciences, tehran, iran 2. assistant professor of infectious diseases, research center of tropical and infectious diseases, kerman university of medical sciences, kerman, iran 3. department of medical parasitology and mycology, school of medicine, shahid beheshti university of medical sciences, tehran, iran received: february 2018; accepted: june 2018; published online: 19 june 2018 abstract: introduction: febrile neutropenic patients are at risk of serious infections. the aim of the present study is to identify the frequency, species, and susceptibility patterns of candidemia in febrile neutropenic patients. methods: this cross-sectional study was conducted on febrile neutropenic patients suspected with candidemia who had been referred to 3 educational hospitals during 9 months. results: the blood samples of 80 febrile neutropenic patients with the mean age of 48±16.6 years were studied (60% female). five (6.25%) episodes of candidemia were identified. the underlying disease was acute myeloid leukemia in 4 (80%) cases and all 5(100%) cases had central venous catheter and were receiving prophylactic ciprofloxacin and acyclovir. 100% of isolates were found to be susceptible to voriconazole, 80% to caspofungin, 60% to amphotericin b, and 40% to fluconazole. conclusion: the frequency of candidemia among the studied febrile neutropenia patients was 6.25%, with 80% mortality rate, and the most frequently identified yeast was candida albicans (100% susceptible to voriconazole). keywords: candidemia; febrile neutropenia; antifungal agents; drug resistance, multiple, fungal © copyright (2018) shahid beheshti university of medical sciences cite this article as: yousefi m, yadegarynia d, lotfali e, arab-mazar z, ghajari a, fatemi a. candidemia in febrile neutropenic patients; a brief report. 2018; 6(1): e39. 1. introduction f ebrile neutropenic patients are at risk of serious infections (1). generally, bacteria are responsible for bloodstream infections (bsis), but, 8% of all cases of infectious agents are candida spp. (2, 3). candida spp. that cause candidemia are the fourth most common agent of bsis and the fifth most common cause of nosocomial infection (4, 5). candida albicans is the most important cause of bsis; however 45% are caused by non-albicans species such as candida glabrata, candida krusei, candida parapsilosis, and candida tropicalis (6, 7). it appears that infection caused by species of candida is associated with a high crude mortality rate, globally (40% in the ∗corresponding author: ensieh lotfali; department of medical parasitology and mycology, school of medicine, shahid beheshti university of medical sciences, tehran, iran, tel: +98-2122439963 fax: +98-2122439964 e-mail: ensiehlotfali@sbmu.ac.ir. united states)(8). the epidemiology of candidemia has been extensively studied in developed countries, but there is a lack of data in developing ones. the aim of the present study is to identify the frequency, species, and susceptibility patterns of candidemia in febrile neutropenic patients. 2. methods 2.1. study design and setting this cross-sectional study was conducted on febrile neutropenic patients who had been referred to khatam-alanbia, shohadaye tajrish, and taleghani educational hospitals, tehran, iran, from november 2016 to august 2017. the ethical committee of shahid beheshti university of medical sciences approved this study under the code: ir.sbmu.retech.rec.1396.192. all enrolled participants were informed about the study and written informed consent was obtained from them. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefi et al. 2 2.2. participants febrile neutropenic patients suspected of candidemia (based on clinical symptoms), referred to emergency departments or hospitalized in intensive care units (9) of the mentioned hospitals were enrolled to the study. patients who had prolonged fever in spite of receiving broad-spectrum antibiotics for more than four days were considered as suspicious to candidemia. patients with chronic neutropenia were excluded from this study since the incidence of neutropenia is unpredictable, and difficult to clearly identify and determine. there was not any sex or age limitation. 2.3. data gathering demographic and clinical data were collected including age, sex, duration of stay in icu, current history of broadspectrum antibiotic therapy (for > 4 days), antifungal therapy, underlying diseases, and outcomes of sur–gical procedures. source of data was the patient’s profile. an assistant professor of infectious diseases (dr. yousefi) was responsible for selecting suspected cases. neutropenia was defined as neutrophil count <500/mm3 or <1000/mm3 with a predicted decrease to <500/mm3 and fever was defined as single elevation in oral temperature to ≥ 38.30 ◦c or a temperature of ≥ 38 âřc for ≥ 1 hour (10). 2.4. cultures 10 ml of venous blood sample were obtained for each patient aseptically via venipuncture according to a standard technique by using a sterile syringe after skin disinfection. culture vials were placed in the bactec 9120 system (becton dickinson microbiology systems, maryland, de, usa), and were controlled automatically every 10 minutes. the bactec bottles that showed a sign of fungal growth were sub-cultured on the plates with the bhi agar (merck, germany) and sabouraud dextrose agar with chloramphenicol (sc) (merck, germany), separately. chrom agar candida medium (chrom agar microbiology, paris, france) was used for sub-culture of isolates, incubated at 35 ◦c for 48 h and for preliminary species identification, production of specific colony colors were analyzed. its1 and its4 universal primers were used for polymerase chain reaction (pcr) and dna sequencing was also performed. 2.5. susceptibility testing in vitro antifungal susceptibility test of the candida iso–lates against amphotericin b (amb) (sigma-aldrich, usa.), fluconazole (flu) (sigma-aldrich, usa.), voriconazole (vor) (pfizer central research, uk), and caspofungin (cas) (merck, usa.) were performed using micro-dilution method. 2.6. statistical analysis statistical analyses were performed using spss software version 21.0. the findings were reported using descriptive statistics such as mean ± standard deviation or frequency and percentage. 3. results: 153 blood samples were collected from 80 febrile neutropenic patients (38 blood samples from emergency departments and 115 from icus). the mean age of the patients was 48±16.6 years (60% female). five (6.25%) episodes of candidemia were identified during the study period. baseline characteristics and outcome of patients with positive blood culture are summarized in table 1. the underlying disease was acute myeloid leukemia in 4 (80%) cases and all 5(100%) cases had central venous catheter and were receiving prophylactic ciprofloxacin and acyclovir. the mean dura-tion of hospital and icu stay in patients with candidemia were 42±5.4 and 26±4.9 days, respectively. table 2 shows the in vitro susceptibility of 5 candida spp. strains against antifungal agents. 100% of isolates were found to be susceptible to voriconazole, 80% to caspofungin, 60% to amphotericin b, and 40% to fluconazole. 4. discussion based on the findings, the frequency of candidemia among the studied febrile neutropenia patients was 6.25%, with 80% mortality rate, and the most frequently identified yeast was candida albicans (100% susceptible to voriconazole). the fourth most common pathogen isolated from the blood of icu patients is candida albicans, with an attributed mortality range between 20–30%. (11-13). however, during recent years, the incidence of candida spp. infections other than candida albicans has significantly increased and candida parapsilosis is currently one of the main causes of invasive candidiasis (14-16). the estimated rate of candidemia among icu admitted patients is between 0.5–32 cases per 1,000 admissions (17, 18). ghahri et al. identified candida parapsilosis as the most prevalent candida spp. from the blood samples of patients with candidemia in iran; but this was not the case in our study (14). according to antifungal susceptibility tests, the most active antifungal drug in isolated candida species was vor; this result was similar to a study by labbe et al. (19). a study by pfaller et al. on in vitro susceptibility results for 1,184 isolates showed that vor was considerably more potent than flu (4). we also found similar results showing that 100% of candida isolates were sensitive to vor. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e39 table 1: baseline characteristics and outcome of patients with positive blood culture variables case 1 case 2 case 3 case 4 case 5 sex female female female male male age (year) 61 34 26 48 71 hospitalization (day) 44 50 34 43 38 icu admission (day) 28 35 23 24 21 underlying disease aml aml aml aml all prophylaxis ciprofloxacin + + + + + acyclovir + + + + + fluconazole + – + – + itraconazole – + – + – co-trimoxazole – – – – + medical device cvc cvc cvc cvc mv, cvc candida spp. c. albicans c. albicans c. albicans c. albicans c. glabrata outcome died died survived died died icu: intensive care unit; cvc: central venous catheter; mv: mechanical ventilation; all: acute lymphoblastic leukemia; aml: acute myeloid leukemia. table 2: in vitro susceptibility test results of the 5 candida spp. strains against 4 antifungal agents. antifungal agent susceptible dose dependent resistant fluconazole 2 (40) 3 (60) 0 (0) voriconazole 5 (100) 0 (0) 0 (0) amphotericin b 3 (60) 1 (20) 1 (20) caspofungin 4 (80) 0 (0) 1 (20) data were reported as number (%). this investigation showed that flu has the highest mic gm (2.3); this result is similar to the study by lobbe et al. that reported the highest mic for flu compared to other azole antifungal drugs such as vor, ravuconazole, itraconazole, and posaconazole (19). a study by pappas pg et al. proposed that in patients with positive blood cultures that become positive more than 48 hours after collection, flu should probably be avoided; and it is more likely that patients are infected by candida glabrata (20). a delay of ≥12 hours in the initial empiric antifungal treatment was associated with higher hospital mortality (21). it seems that empiric antifungal therapy needs to be started early in order to decrease morbidity and mortality. 5. limitations this study had several limitations including the short duration of survey followed by a low number of positive patients. therefore, it was difficult to compare and interpret the findings, especially antifungal susceptibility patterns. however, based on the findings of this study, candidemia should be considered a significant problem in febrile neutropenic patients. 6. conclusion based on the finding, the frequency of candidemia among the studied febrile neutropenia patients was 6.25%, with 80% mortality rate, and the most frequently identified yeast was candida albicans (100% susceptible to voriconazole). 7. appendix 7.1. acknowledgements the authors would like to express their gratitude to those who participted in data collection in selected hospitals. this article has been extracted from the thesis written by dr. maysam yousefi in school of medicine, shahid beheshti university of medical sciences. 7.2. author contribution ensieh lotfali, davood yadegarynia, meysam yousefi designed the study. zahra arab-mazar participated in acquisition of data. ali ghajari and alireza fatemi participated in management of data. all authors approved the final version of the manuscript to be published. 7.3. funding/support we would like to express our gratitude to infectious diseases and tropical medicine research center, shahid bethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. yousefi et al. 4 heshti university of medical sciences for financially supporting this research. 7.4. conflict of interest the authors declare that they have no conflicts of interest. references 1. talcott ja, siegel r, finberg r, goldman l. risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. journal of clinical oncology. 1992;10(2):316-22. 2. santucci s, gobara s, santos c, fontana c, levin a. infections in a burn intensive care unit: experience of seven years. journal of hospital infection. 2003;53(1):6-13. 3. lotfi n, shokohi t, nouranibaladezaei sz, omran an, kondori n. high recovery rate of non-albicans candida species isolated from burn patients with candidemia in iran. jundishapur journal of microbiology. 2015;8(10). 4. pfaller m, diekema d, jones r, sader hs, fluit a, hollis r, et al. international surveillance of bloodstream infections due tocandida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the sentry antimicrobial surveillance program. journal of clinical microbiology. 2001;39(9):3254-9. 5. yapar n. epidemiology and risk factors for invasive candidiasis. therapeutics and clinical risk management. 2014;10:95. 6. zirkel j, klinker h, kuhn a, abele-horn m, tappe d, turnwald d, et al. epidemiology of candida blood stream infections in patients with hematological malignancies or solid tumors. medical mycology. 2012;50(1):50-5. 7. das i, nightingale p, patel m, jumaa p. epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the uk. international journal of infectious diseases. 2011;15(11):e759-e63. 8. edmond mb, wallace se, mcclish dk, pfaller ma, jones rn, wenzel rp. nosocomial bloodstream infections in united states hospitals: a three-year analysis. clinical infectious diseases. 1999;29(2):239-44. 9. voiculescu m, iliescu l, ionescu c, micu l, ismail g, zilisteanu d, et al. a cross-sectional epidemiological study of hbv, hcv, hdv and hev prevalence in the subcarpathian and south-eastern regions of romania. j gastrointestin liver dis. 2010;19(1):43-8. 10. yadegarynia d, fatemi a, mahdizadeh m, movahhed rk, alizadeh ma. current spectrum of bacterial infections in patients with nosocomial fever and neutropenia. caspian journal of internal medicine. 2013;4(3):698. 11. wisplinghoff h, bischoff t, tallent sm, seifert h, wenzel rp, edmond mb. nosocomial bloodstream infections in us hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. clinical infectious diseases. 2004;39(3):309-17. 12. zorgani a, franka r, zaidi m, alshweref u, elgmati m. trends in nosocomial bloodstream infections in a burn intensive care unit: an eight-year survey. annals of burns and fire disasters. 2010;23(2):88. 13. zaoutis t. candidemia in children. current medical research and opinion. 2010;26(7):1761-8. 14. ghahri m, mirhendi h, zomorodian k, kondori n. identification and antifungal susceptibility patterns of candida strains isolated from blood specimens in iran. archives of clinical infectious diseases. 2013;8(3). 15. krcmery v, barnes a. non-albicans candida spp. causing fungaemia: pathogenicity and antifungal resistance. journal of hospital infection. 2002;50(4):243-60. 16. nicholson a, rainford l. the epidemiology of fungaemia at the university hospital of the west indies, kingston, jamaica. west indian medical journal. 2009;58(6):580-4. 17. tortorano a, caspani l, rigoni a, biraghi e, sicignano a, viviani m. candidosis in the intensive care unit: a 20year survey. journal of hospital infection. 2004;57(1):813. 18. kett dh, azoulay e, echeverria pm, vincent j-l. candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. critical care medicine. 2011;39(4):665-70. 19. labbe a-c, pepin j, patino c, castonguay s, restieri c, laverdiere m. a single-centre 10-year experience with candida bloodstream infections. canadian journal of infectious diseases and medical microbiology. 2009;20(2):45-50. 20. pappas pg, kauffman ca, andes d, benjamin dk, calandra tf, edwards je, et al. clinical practice guidelines for the management candidiasis: 2009 update by the infectious diseases society of america. clinical infectious diseases. 2009;48(5):503-35. 21. morrell m, fraser vj, kollef mh. delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. antimicrobial agents and chemotherapy. 2005;49(9):3640-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion limitations conclusion appendix references emergency. 2018; 6 (1): e55 or i g i n a l re s e a rc h screening performance of ultrasonographic b-lines in detection of lung contusion following blunt trauma; a diagnostic accuracy study saeed abbasi1, hossein shaker1, fariba zareiee1, davood farsi1, peyman hafezimoghadam1, mahdi rezai1, babak mahshidfar1, mani mofidi1∗ 1. emergency medicine management research center, iran university of medical sciences, rasoul akram hospital, tehran, iran. received: march 2018; accepted: august 2018; published online: 2 september 2018 abstract: introduction: chest ultrasonography is routinely used in evaluation of chest trauma for diagnosis of pulmonary injury. this study aimed to evaluate the accuracy of b-lines for diagnosing lung contusion in patients with blunt trauma of the chest. methods: trauma patients who met the inclusion criteria were enrolled in the study and underwent ultrasonography by trained emergency medicine residents. ultrasound results were recorded in terms of number of b-lines and the existence of peripheral parenchymal lesion (ppl). after ultrasound, the patient underwent chest x-ray and chest ct scan (as reference test) and screening performance of b-lines and ppl were evaluated. results: 147 patients underwent chest ultrasound. the mean age of the patients was 40.74 ± 18.6 (78.9% male). b-lines>3 had 94.0% (95% ci: 83.45-98.75) sensitivity and 57.7% (95% ci: 47.3-67.7) specificity, b-lines>6 had 90.0% (95% ci: 78.2-96.7) sensitivity and 93.81% (95% ci: 87.0-97.7) specificity, and ppl had 34.0% (95% ci: 21.2-48.8) sensitivity and 100% (95% ci: 96.3-100.0) specificity. composite findings of b-lines>6 + ppl had 92.0% (95% ci: 80.8-97. 8) sensitivity and 93.8% (95% ci: 87.0-97.7) specificity in the diagnosis of lung contusion. conclusion: ppl and b-lines>6 had the highest accuracy in detecting lung contusion. b-line>6 had high sensitivity and specificity and was easy to perform; thus, it seems that b-line>6 could be considered as an alternative screening tool in detection of lung contusion. keywords: diagnosis; emergency service, hospital; diagnostic imaging; ultrasonography; thoracic injuries © copyright (2018) shahid beheshti university of medical sciences cite this article as: abbasi s, shaker h, zareiee f, farsi d, hafezimoghadam p, rezai m, mahshidfar b, mofidi m. screening performance of ultrasonographic b-lines in detection of lung contusion following blunt trauma; a diagnostic accuracy study. compr j emerg med. 2018; 6(1): e55. 1. introduction chest trauma and its complications are responsible for about 25% of deaths due to blunt trauma. lung contusion is a common complication of blunt chest trauma as it happens in 30 to 75% of the cases (1). lung contusion is an independent risk factor of acute respiratory distress syndrome (ards), pneumonia, long-term respiratory failure and is associated with 10 to 25% mortality rate (2-4). early and accurate diagnosis and proper management of pulmonary contusion in emergency department have a significant influence on morbidity and mortality of these patients (3). in the beginning, ∗corresponding author: mani mofidi; emergency medicine management research center, rasoul akram hospital, tehran, iran. email: manimofidi@yahoo.com tel: 00989122263218 chest radiography (cxr) is traditionally done to diagnose probable lung contusion, but identification of opacity and its size needs time and generally takes 6 to 48 hours, so lung contusion usually can’t be diagnosed in the early phase via cxr (4, 5). chest computed tomography (ct) scan is more sensitive than cxr and is considered as the gold standard technique for detecting lung contusion (6). chest ct scan reveals the exact distribution and size of pulmonary injury (7). lung ultrasound is increasingly used as standard trauma care in emergency departments (ed). it can detect alveolar consolidations, interstitial syndrome, pulmonary embolisms and pneumothorax (8). prompt and accurate bedside detection of thoracic disorders is its advantage compared to other diagnostic modalities (9). ultrasound is a method with high precision for detecting interstitial edema, which is used in diagnosis of lung contusion based on local interstitial edema this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. abbasi et al. 2 due to trauma. two studies conducted by soldati and shadia found that chest ultrasonography had a high sensitivity and precision in diagnosis of lung contusion in patients with blunt trauma (10, 11). b-lines are the important finding in chest sonography of lung contusion, but the number of blines that can be used to diagnose is not known. one study believed that less than 3 b-lines could be seen in an uninjured lung (9) and the other one stated the lung ultrasound would be normal in presence of less than 6 b lines (10). a recent meta-analysis study has shown ultrasonography is a preferred screening modality in detection of pulmonary contusion compared to chest radiography, but the eligible studies didn’t mention the number of b-lines that indicated pulmonary contusion (12). the aim of this study was to evaluate the accuracy of b-line in diagnosing of lung contusion in patients with blunt trauma to the chest. 2. methods 2.1. study design and setting this diagnostic accuracy study was conducted in the eds of rasool-e-akram and sina hospitals, tehran, iran, from 1 august 2014 to 1 june 2014. the study was approved by the ethics committee of tehran university of medical sciences with the code number of 142, 2013. informed consent was obtained from patients or their relatives. 2.2. participants the study participants included patients with blunt chest trauma brought to eds of the mentioned hospitals. we consecutively enrolled eligible patients in the study. patients suffering from chest trauma or multiple traumas with chest involvement who were aged more than 18 years old and gave consent to participate in the study were included. in addition, patients with hemodynamic instability, patients with diagnosis of pneumothorax, subcutaneous emphysema interfere with the ultrasound images, patients with a body mass index (bmi) >30, pregnant patients, patients without co-operation for ultrasonography, and patients did not give consent to participate in the study or refrained from continuing to cooperate with investigators were excluded. 2.3. imaging bedside lung ultrasound was performed during the initial assessment with simultaneous resuscitation after the arrival of the patient with blunt chest trauma to the ed and then all patients were sent for cxr and ct scan immediately. we used ultrasound scanner (sonoace x8, samsung medison, seoul, korea) equipped with a 7.5 to 10 mhz convex transducer with 5-inch wide field. ultrasound was performed by six emergency medicine residents who were familiar with ultrasound. first, a one-hour theoretical course was held figure 1: a: lung zones in chest ultrasound (with permission from credit a, tozer j, vitto m, joyce m, taylor l. clinical ultrasound, a pocket manual. springer, 2018). b: lung contusion with more than 6 b-lines (arrow). for them. thereafter, bedside tutoring was given by a faculty member of emergency medicine, including at least 25 chest ultrasounds. each patient was scanned by one of emergency residents. ultrasonography was done according to the method described by lichtenstein (13, 14). each lung area was divided into 4 regions. the upper and lower parts of the anterior and postero-lateral regions of chest walls were scanned with the patient in supine position. we could only examine patients in supine position because of trauma condition. the multiple zones that were examined in ultrasonography are shown in figure 1-a. in the normal lung, ultrasound was carried out with the probe longitudinally placed in the spaces between the ribs; these indicators can be seen as lung sliding on a line with echogenic view that synchronizes with ventilation. this sign can be seen when visceral pleura moves on the parietal pleura, which rules out pneumothorax. lung sliding is not always evident and pleural contact and lung movement may be demonstrated by m mode, which is called seashore sign, and is characterized by horizontal lines (“waves”) representing the static chest wall and a scattered region (“sand”) formed by the dynamic artifacts beyond the pleural line, for which pneumothorax was ruled out. the pleural line was defined as a horizontal hyperechoic line visible at 0.5 cm below the rib line. horizontal lines arising from and parallel to the pleural line were called a lines; roughly vertical lines arising from and perpendicular to the pleural line were called b lines. during the ultrasound, the probe was placed in the anterior and lateral wall and the rear area around the posterior axillary line. those who could not move were placed in the supine position. the results were interpreted as follows: 1. normal ultrasound: lung sliding in addition to less than this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e55 figure 2: study flow chart. *: equal or less than 6 b-lines, ∈: more than 6 b-lines, £: true negative, λ: true positive. 3 b-lines on the scanned surface and the absence of any peripheral consolidation. 2. lung contusion in ultrasound: the presence of one of the following criteria alone or both; a) alveolo-interstitial syndrome (ais) by the presence of multiple b-lines (more than 3) that originate from pleural line in a person with no clinical cardiopulmonary signs (figure 1-b). b) peripheral parenchymal lesion (ppl), defined by the presence of c-lines: hypoechoic subpleural focal images with or without pleural line gap (10). the chest ct scan and cxr images were analyzed and reported by an attending radiologist. obviously, physicians performing ultrasound were unaware of the ct and cxr findings. the radiologist was also unaware of the result of the ultrasound performed by the emergency residents. all examinations were performed in the same sequence for all patients. 2.4. reference standard after the ultrasound, cxr and chest ct scan (lung and mediastinal aspect) without contrast agent were performed. thoracic ct scan was performed from the apex of the chest to the diaphragm in a 5-mm interval with the patients in the supine position using a 16 multi detector computed tomography (mdct) scanner (sensation 16, siemens, erlangen, germany). ct scanning can detect lung contusion almost immediately following chest trauma and it is the standard criterion for diagnosis of lung contusion. the evidence of contusion in ct images are non-segmental areas of consolidation and ground-glass opacification that predominantly involve the lung and are directed deeply into the area of trauma, often sparing 1 to 2 mm of subpleural lung parenchyma adjacent to the injured chest wall (15). 2.5. data gathering patients’ demographic data as well as ultrasonography, cxr, and chest ct scan findings were collected by trained emergency medicine residents using a predesigned checklist. 2.6. statistical analysis the sample size was calculated based on hosseini et al. (12) study considering α-error equal to 0.05, power equal to 80%, prevalence of lung contusion equal to 30%, and presumed this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. abbasi et al. 4 table 1: baseline characteristics of studied patients and imaging findings regarding the presence or absence of lung contusion variable values sex male 116 (78.9) female 31 (21.1) age (year) mean ± sd 40.7 ± 18.6 mechanism of trauma accident 100 (68.0) falling 32 (21.8) direct impact 15 (10.2) chest x-ray positive 13 (8.8) negative 134 (91.2) chest ct scan positive 50 (34.1) negative 97 (65.9) ultrasonography (number of b-lines) positive (3 – 6) 36 (24.5) positive (> 6) 51 (34.7) negative (≤ 3) 60 (40.8) ultrasonography (ppl) positive 17 (11.6) negative 130 (88.4) data are reported as mean ± standard deviation (sd) or frequency (%). ppl: peripheral parenchymal lesion. sensitivity of 92%. the estimated sample size obtained was 140 patients. all statistical analyses were performed using spss 16.0 (spss inc. chicago, il, u.s.a.). quantitative descriptive data was reported using mean ± standard deviation (sd), and qualitative data as frequency (%). quantitative variables such as age and time intervals were assessed regarding normality using one-sample kolmogorov-smirnov test, and t-test was used for analytical examination. to determine the diagnostic value of ultrasound in lung contusion, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio, as well as area under the receiver operating characteristic (roc) curve were calculated. the level of significance was considered less than 5%. 3. results 3.1. baseline characteristics of participants one hundred sixty-one patients were evaluated, 14 patients were secondarily excluded, and finally 147 patients with blunt chest trauma were enrolled (figure 2). the mean age of the patients was 40.74 ± 18.6 (18 90) years (78.9% male). baseline characteristics of patients as well as thoracic imaging findings are shown in table 1. 96 (65.3%) cases had 6 or less b-lines and 51 (34.7%) had more than 6 b-lines. ppl in favor of lung contusion was observed in 17 (11.6%) patients, among them 16 cases had more than 6 b-lines and only one case had 3 to 6 b-lines. chest ct scans of 50 (34%) patients showed definite lung contusion. in eighteen patients, one ninth to three ninths of lung were injured. half of them (25 patients) had four ninths to six ninths involvement and 7 patients were severely injured (seven ninths to nine ninths involvement). 3.2. screening performance characteristics of tests out of the 51 patients who had more than 6 b-lines on ultrasound, 45 patients had definite contusion and six of them did not show any evidence of lung contusion on ct scan. table 2 shows the sensitivity, specificity, positive and negative predictive values and likelihood ratios of sonographic b-lines and ppl in detection of lung contusion. 4. discussion the current study showed acceptable sensitivity and specificity of point of care ultrasound in chest trauma for diagnosis of lung contusion. ppl and more than 6 b-lines had the highest sensitivity and specificity (92.0 and 93.81) in the diagnosis of lung contusion. in addition, when the number of b-lines was >6, it had a good sensitivity and specificity (90.0 and 93.81) in diagnosis of lung contusion. ppl was seen on ultrasound in 17 patients in our study with the sensitivity of 34% (21.21-48.77), and specificity of 100%, which indicated that this is a specific finding in diagnosis of lung contusion. in a study conducted by soldati et al. (10) out of 37 patients diagnosed with lung contusion, 7 had ppl with a sensitivity of 18.9% and specificity of 100%. the study by helmy et al. (11) showed that sensitivity and specificity of ppl in diagnosis of lung contusion were 92.5% and 100%, respectively. the soldati study was more consistent with our results and the notable fact is that the specificity of all three studies was reported to be 100%. in our study, it was found that when more than 3 b-lines was considered as lung contusion, the sensitivity and negative predictive value of the test increased to 94%, but in parallel, specificity and positive predictive value decreased. therefore, consideration of more than 3 blines leads to over-diagnosis of lung contusion. when more than 6 b-lines in ultrasound were considered as lung contusion, specificity and positive predictive value increased significantly; this reduced the probability of false positives. in this study, only 6 false positives were reported, which were diagnosed in chest ct scans as one case of pulmonary fibrosis and one case of pneumonia. patients with diffuse parenchymal lung disease (dpld) had positive b-lines on ultrasound as defined in a study conducted by reibig et al (7). four other cases diagnosed as b-line by mistake could be z and e lines. z lines are vertical lines arising from the pleural line but not this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e55 table 2: diagnostic accuracy of sonographic b-lines and peripheral parenchymal lesion (ppl) in detection of lung contusion considering non-contrast chest ct scan as gold standard variable specificity sensitivity ppv npv lr+ lr− b-line>3 tp=47 tn=56 57.73 94.0 53.41 94.92 2.22 0.10 fp=41 (47.28-67.7) (83.45-98.75) (42.46-64.12) (85.85-98.94) (1.74-2.84) (0.03-0.32) fn=3 b-line>6 tp=45 tn=91 93.81 90.0 88.24 94.79 14.55 0.11 fp=6 (87.02-97.70) (78.19-96.67) (76.13-95.56) (88.26-98.29) (6.67-31.76) (0.05-0.25) fn=5 pll tp=17 tn=97 100.0 34.0 100.0 74.62 infinite 0.66 fp=0 (96.27-100) (21.21-48.77) (80.49-100) (66.24-81.84) (0.54-0.81) fn=33 ppl + b-line>6 tp=46 tn=91 93.81 92 88.46 95.79 14.87 0.09 fp=6 (87.02-97.7) (80.77-97.78) (76.56-95.65) (89.57-98.84) (6.82-34.42) (0.03-0.22) fn=4 ppl + b-line>3 tp=46 tn=56 57.73 92 52.87 93.33 2.18 0.14 fp=41 (47.28-67.7) (80.77-97.78) (41.87-63.67) (83.8-98.15) (1.7-2.79) (0.05-0.36) fn=4 cxr tp=13 tn=97 100.0 26.0 100.0 72.39 infinite 0.74 fp=0 (96.27-100) (14.63-40.34) (75.29-100) (64-79.76) (0.63-0.87) fn=37 data are presented with 95% confidence interval. tn: true negative; tp: true positive; fp: false positive; fn: false negative; ppv: positive predictive value; npv: negative predictive value; lr: likelihood ratio. reaching the distal edge of the screen. e lines are vertical lines that reach the distal edge of the screen but do not arise from the pleural line (10). the above-mentioned studies (10, 11) in traumatic patients reported the sensitivity and specificity of b-line>6 in diagnosis of lung contusion as “94.6% and 96%” and “97.5% and 90%”, respectively, which were consistent with our results. in a study by m. rocco et al., patients with chest trauma who were under mechanical ventilation in the icu were assessed for pleural effusion and lung contusion by ultrasound at the time of admission to the icu. after 48 hours, the authors reported the sensitivity and specificity of ultrasonography in diagnosis of pulmonary contusion to be “86% and 97%” against “89% and 89%” on arrival (8). in our study, the diagnostic value of pll with the b-line>6 was the highest in diagnosis of lung contusion, with only 2% higher sensitivity when compared to b-line>6 alone. given that education and diagnosis of b-line>6 is far easier than ppl, it is advised that b-line>6 alone be used as a reliable method for diagnosis of lung contusion. our study showed that chest xray has low sensitivity and high specificity (26 and 100%) in diagnosis of pulmonary contusion. in a study by mcgonigal et al. entitled “supporting role of lung ct scan in management of patients with blunt trauma”, sensitivity of chest x-ray for lung contusion was reported to be 40% (16). in addition, hemly et al. showed that chest x-ray has low sensitivity and high specificity, 40% and 90%, respectively (11). soldati et al. had also reported 27% sensitivity and 100% specificity for chest x-ray, which are consistent with our results (10). chest radiography is frequently used for evaluation of traumatic patients. although chest radiography is valuable, based on existing studies, its sensitivity in diagnosis of lung contusion is low and needs several hours to diagnose the lesion (12, 17). ct scan is the gold standard method in chest trauma, but generally needs the patient to be transferred; so, performing it is not possible in an unstable patient. in addition, the cost and radiation of ct scan is high (18). high sensitivity and specificity is considered the advantage of ultrasound. it seems that sonographic b-lines > 6 could be conthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com s. abbasi et al. 6 sidered as a reliable alternative tool in diagnosis of lung contusion. 5. limitation one of the limitations of the current study was that we excluded the patients with the bmi more than 30, thus the results of study could not be generalized to these patients. sensitivity and specificity of ultrasound could be affected by obesity and fat tissue. also, ultrasound was performed by six emergency residents. they attended a similar education course (lecturing and hands on) but we did not compare them with each other and it could be basically a limitation. 6. conclusion ppl and b-lines>6 had the highest accuracy in detecting lung contusion. b-line>6 had high sensitivity and specificity and was easy to perform; thus, it seems that b-line> could be considered as an alternative screening tool in detection of lung contusion. 7. appendix 7.1. acknowledgements this article was part of dr. fariba zareiee’s thesis, who was an emergency medicine resident at the time of the study. the authors would like to thank the nurses of ed at rasoul-eakram and sina hospitals. 7.2. author contribution all the authors meet the standard authorship criteria according to the recommendations of international committee of medical journal editors. authors’ orcids saeed abbasi: 0000-0001-6024-1576 hossein shaker: 0000-0003-0651-5702 fariba zareiee: 0000-0001-9476-7736 davood farsi: 0000-0002-8366-2477 peyman hafezimoghadam: 0000-0003-0599-369x mahdi rezai: 0000-0003-0486-5717 babak mahshidfar: 0000-0001-6174-8432 mani mofidi: 0000-0002-0122-3703 7.3. funding/support no funds have been received for carrying out this project. 7.4. conflict of interest there are no conflicts of interest to declare. references 1. simon b, ebert j, bokhari f, capella j, emhoff t, hayward t, 3rd, et al. management of pulmonary contusion and flail chest: an eastern association for the surgery of trauma practice management guideline. the journal of trauma and acute care surgery. 2012;73(5 suppl 4):s35161. 2. hoff sj, shotts sd, eddy va, morris ja, jr. outcome of isolated pulmonary contusion in blunt trauma patients. the american surgeon. 1994;60(2):138-42. 3. cobanoglu u, melek m, edirne y. chest radiography diagnosis of pulmonary contusion is associated with increased morbidity and mortality 2010 march 01. 24-9 p. 4. wanek s, mayberry jc. blunt thoracic trauma: flail chest, pulmonary contusion, and blast injury. critical care clinics. 2004;20(1):71-81. 5. allen gs, coates ne. pulmonary contusion: a collective review. the american surgeon. 1996;62(11):895-900. 6. omert l, yeaney ww, protetch j. efficacy of thoracic computerized tomography in blunt chest trauma. the american surgeon. 2001;67(7):660-4. 7. reissig a, kroegel c. transthoracic sonography of diffuse parenchymal lung disease: the role of comet tail artifacts. journal of ultrasound in medicine: official journal of the american institute of ultrasound in medicine. 2003;22(2):173-80. 8. rocco m, carbone i, morelli a, bertoletti l, rossi s, vitale m, et al. diagnostic accuracy of bedside ultrasonography in the icu: feasibility of detecting pulmonary effusion and lung contusion in patients on respiratory support after severe blunt thoracic trauma. acta anaesthesiologica scandinavica. 2008;52(6):776-84. 9. lichtenstein da, meziere ga. relevance of lung ultrasound in the diagnosis of acute respiratory failure: the blue protocol. chest. 2008;134(1):117-25. 10. soldati g, testa a, silva fr, carbone l, portale g, silveri ng. chest ultrasonography in lung contusion. chest. 2006;130(2):533-8. 11. helmy s, beshay b, hady ma, mansour a. role of chest ultrasonography in the diagnosis of lung contusion. egypt j chest dis tu. 2015;64(2):469-75. 12. hosseini m, ghelichkhani p, baikpour m, tafakhori a, asady h, haji ghanbari mj, et al. diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and metaanalysis. emergency. 2015;3(4):127-36. 13. d l. general ultrasound in the critically ill. 2nd ed ed. germany: springer-verlag; 2005. 14. lichtenstein d, meziere g, biderman p, gepner a, barre o. the comet-tail artifact. an ultrasound sign of alveolarinterstitial syndrome. american journal of respiratory this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 7 emergency. 2018; 6 (1): e55 and critical care medicine. 1997;156(5):1640-6. 15. johnson sb. tracheobronchial injury. seminars in thoracic and cardiovascular surgery. 2008;20(1):52-7. 16. mcgonigal md, schwab cw, kauder dr, miller wt, grumbach k. supplemental emergent chest computed tomography in the management of blunt torso trauma. the journal of trauma. 1990;30(12):1431-4; discussion 45. 17. paydar s, johari hg, ghaffarpasand f, shahidian d, dehbozorgi a, ziaeian b, et al. the role of routine chest radiography in initial evaluation of stable blunt trauma patients. the american journal of emergency medicine. 2012;30(1):1-4. 18. mayo jr, aldrich j, muller nl. radiation exposure at chest ct: a statement of the fleischner society. radiology. 2003;228(1):15-21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references emergency. 2018; 6 (1): e54 or i g i n a l re s e a rc h burn-induced oxidative stress and serum glutathione depletion; a cross sectional study arash beiraghi-toosi1,2, roya askarian3, faezeh sadrabadi haghighi3, mohammad safarian4, fereshteh kalantari1, seyed isaac hashemy1∗ 1. surgical oncology research centre, mashhad university of medical sciences, mashhad, iran. 2. department of plastic surgery, imam reza hospital, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 3. department of clinical biochemistry, faculty of medicine, mashhad university of medical sciences, mashhad, iran. 4. department of nutrition, faculty of medicine, mashhad university of medical sciences, mashhad, iran. received: april 2018; accepted: august 2018; published online: 31 august 2018 abstract: introduction: several studies have shown the role of oxidative stress in pathophysiology of burn injuries. this study aimed to evaluate the changes of oxidant-antioxidant levels during the week following burn injuries and its correlation with grade of burn. methods: in this prospective cross-sectional study, changes of total glutathione, reduced glutathione (gsh), oxidized gsh (gssg), gsh/gssg ratio, as well as pro-oxidant-antioxidant balance (pab) were investigated on the 1st, 2nd and 7th days of admission in patients with > 15% burns. results: 40 patients with the mean age of 21.1 ± 14.5 were studied (47.5% male). more than 50% of patients were in the 18 – 55 years age range and over 70% had 20% – 60% grade of burn. total serum glutathione level and gsh had significant decreasing trends (p < 0.001) and gssg and gsh/gssg ratio had increasing trends (p < 0.001). no significant correlation was observed between serum gsh level and the total body surface area (tbsa) of burn injury (r = 0.047; p = 0.779). the evaluation of pab and its correlation with tbsa showed a significant and direct association between them on the 1st (coefficient = 0.516; p = 0.001), 2nd (coefficient = 0.62; p <0.001), and 3rd (coefficient = 0.471; p = 0.002) day of follow up. conclusion: according to this study, the redox perturbation occurred in burn injury which was measured and proved by decreased gsh/gssg ratio as well as the shift of pab in favour of oxidants. besides, since pab positively correlated with the severity of dermal damage, it might suggest the application of antioxidants as a part of therapeutic protocol for which the dosage should be proportionate to the surface area of the damaged skin. keywords: oxidative stress; oxidants; antioxidants; glutathione; burns © copyright (2018) shahid beheshti university of medical sciences cite this article as: beiraghi-toosi a, askarian r, sadrabadi haghighi f, safarian m, kalantari f, hashemy seyed i. burn-induced oxidative stress and serum glutathione depletion; a cross sectional study. emergency. 2018; 6(1): e54. 1. introduction burn injury is a kind of inflammatory disease in which, besides the local dermal damages, systemic complications such as systemic inflammatory response syndrome, multiple organ failure and sepsis, which are the leading causes of morbidity and mortality, may occur (1, 2). different factors such as inflammatory responses are involved in the pathophysiology of these systemic complications. oxidative stress is ∗corresponding author: seyed isaac hashemy; surgical oncology research centre, mashhad university of medical sciences, mashhad, iran. email: hashemyi@mums.ac.ir tel: +98-9158112664 one of these factors, which happens due to the formation of free radicals at the area of injury due to intravascular stimulation of neutrophils and increased xanthine oxidase activity (3, 4). the subsequent transportation of these free radicals to distant parts through blood flow may explain one of the mechanisms by which other organs such as liver, heart and lungs can get damaged in patients with burn injury (5). lalonde et al. even suggested a causal relationship between increased redox perturbation and inflammation (6). these damages are because of the high reactivity of free radicals, including both reactive oxygen species (ros) and reactive nitrogen species (rns), which react with and oxidize cellular molecules such as proteins, lipids and nucleic acids this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. beiraghi-toosi et al. 2 (7, 8) leading to a wide variety of diseases including cancers, autoimmune diseases, cardiovascular diseases, etc (914). on the other hand, the body is equipped with enzymatic as well as non-enzymatic antioxidants to recuperate the redox homeostasis (15-18). glutathione, a tripeptide, is such a molecule, which plays an important role in providing and maintaining a reduced intracellular environment, which is necessary for cell survival (19). during oxidative stress, when pro-oxidant-antioxidant balance (pab) is disrupted in favour of the former, reduced glutathione (gsh) is oxidized to the form of gssg, and gsh/gssg ratio, which is normally about 100/1 in cells, decreases to values of about 10:1 and even 1:1 (20-23). this study aimed to investigate if oxidative stress happens during burn injury, how it proceeds during the first week of injury and whether it correlates with the severity of dermal damage. for this purpose, two markers of oxidative stress were selected: the gsh/gssg ratio and pab. the latter is a newly-established method through which the whole redox status can be investigated using a simple method (24). 2. methods 2.1. study design and setting this prospective cross-sectional study was conducted on burn patients who were hospitalized in imam reza hospital, mashhad, iran, during a one-month period from february 2016 to march 2016. the changes of total glutathione, gsh, gssg, as well as gsh/gssg ratio were investigated on the 1st, 2nd and 7th days after a thermal burn injury. this project was ethically approved by the research council of mashhad university of medical sciences (code: ir.mums.rec.1388.102), and an informed consent was provided by each patient. 2.2. participants patients with over 15% burn of total body surface area (tbsa) of the second-degree were enrolled using non probability convenience sampling method. those with known systemic diseases such as cardiovascular diseases, diabetes mellitus, smoking, opium addiction, etc. as well as patients with a recent history of consuming antioxidants such as vitamin c and multivitamins in which the redox status could be affected were excluded from this study. 2.3. measurements after careful history taking and clinical examination, the protocol of study was explained to patients or relatives and an informed consent was obtained. blood samples from each patient were collected three times: on the 1st day (during the first 6 hours after the injury), 2nd day (24 hours after the injury), and 7th day of the injury to study serum gsh in both oxidized and reduced forms as well as pab. blood samples were collected free of any anticoagulant, kept at room temperature for 30 minutes to clot. thereafter, the samples were centrifuged at 2000×g for 15 min at 4 ◦c to separate the serum, which was subsequently deproteinated by adding an equal volume of metaphosphoric acid 1 m in distilled water to the sample. after 5 minutes of incubation at 25◦c, the mixture was centrifuged at 3000×g for 5 minutes and the supernatant was collected carefully. the concentration of serum gsh was measured by the method described before by ellman, which is based on the reduction of 5,5’dithiobis-(2-nitrobenzoic acid) (dtnb) by free thiols to 2nitrobenzoic acid anion (tnb–), which is a yellowish compound (22, 27, 28). the absorbance of samples was measured spectrophotometrically at 412 nm, and the concentration of glutathione in each sample was calculated using a standard curve, which had been provided with different concentrations of glutathione (0-15 µm in mes buffer). in order to measure the concentration of gssg, excluding gsh, 10 µl of 2-vinylpyridine 1 m in ethanol was added to 1 ml of deproteinated sample, incubated at 25◦c for 60 min to block free thiols of gsh. subtraction of gssg level from total glutathione concentration equals to gsh level. serum pab was measured before deproteination as described before (24). in brief, it was performed by adding a cation to the tmb (3, 3 ’, 5, 5’-tetramethylbenzidine) solution by peroxidase enzyme. the cationized tmb solution (blue colored) was subsequently reduced by antioxidants present in the sample or standards, and converted to the reduced tmb (colorless). the higher the level of antioxidants in the sample was, the lower the density of blue color would be. for this purpose, the standard curve was prepared by mixing varying percentages of hydrogen peroxide 250 µm and uric acid 3 mm in 10 mm of naoh. the resulting absorption was read at a wavelength of 450 nm. the percentage of burnt tbsa was calculated using the law of lound & browder (25, 26). all materials and reagents were purchased from sigma-aldrich, germany. 2.4. data gathering demographic information (age, sex), vital signs (temperature, heart rate, respiratory rate), and the percentage of tbsa were recorded for all participants using a pre-design check list. there were no missing data. all data were collected prospectively by a trained nurse. laboratory tests were performed by msc students in clinical biochemistry. 2.5. statistical analysis we have performed the kolmogorov-smirnov test to check the normality of data. repeated measures anova, paired sample t-test, and correlation coefficient tests were used to analyse the data. the level of significance was considered as p-value ≤0.05. spss 11.0 software was used for statistical this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e54 figure 1: serum glutathione changes following burn injury on the 1st, 2nd, and 7th day of admission. analysis and data are presented as mean ± standard deviation (sd). 3. results 3.1. baseline characteristics of studied patients 40 patients with the mean age of 21.1 ± 14.5 (3 – 56) were studied (47.5% male). table 1 shows the baseline characteristics of studied patients. more than 50% of patients were in 18 – 55 years age range and > 70% had 20% – 60% burn. 3.2. gsh changes following burn injury figure 1 and table 2 summarize the changes of total serum glutathione level, gsh, gssg, and gsh/gssg ratio during the one week follow-up. total serum glutathione level and gsh had significant decreasing trends (p < 0.001) and gssg and gsh/gssg ratio had increasing trends (p < 0.001). no significant correlation was observed between serum gsh level and the tbsa of burn injury (r = 0.047; p = 0.779). 3.3. pab changes following burn injury the evaluation of pab and its correlation with tbsa showed a significant and direct association between them on the 1st (coefficient = 0.516; p = 0.001), 2nd (coefficient = 0.62; p <0.001), and 3rd (coefficient = 0.471; p = 0.002) day of follow up (figure 2). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. beiraghi-toosi et al. 4 table 1: baseline characteristics of studied patients variables number (%) sex male 19 (47.5) female 31 (52.5) age (years) < 18 16 (40.0) 18 – 35 12 (30.0) 35 – 55 11 (27.5) ≥ 55 1 (2.5) burn grade* (%) <20 3 (7.5) 20 – 40 26 (65.0) 40 – 60 3 (7.5) ≥ 60 8 (20.0) *: calculated using the law of lound & browder. table 2: changes of total serum glutathione level, reduced glutathione (gsh), oxidized glutathione (gssg), and gsh/gssg ratio during the one week follow-up after burn injury among the studied patients variables values p total glutathione (µm) 1s t 10.52 ± 1.38 2n d 4.13 ± 0.96 < 0.001 7t h 3.91 ± 1.18 gsh 1s t 8.05 ± 1.46 2n d 1.32 ± 0.95 < 0.001 7t h 0.55 ± 0.51 gssg 1st 2.46 ± 0.81 2n d 2.81 ± 0.89 < 0.001 7t h 3.37 ± 1.01 gsh/gssg ratio 1st 3.66 ± 1.44 2n d 0.55 ± 0.44 < 0.001 7t h 0.17 ± 0.15 data are presented as mean ± standard deviation. 4. discussion the aim of this study was to determine how the formation of reactive oxygen species and its subsequent oxidative stress proceed during the first week of burn injury; for this purpose, gsh/gssg ratio and pab were chosen as the markers of the redox status. based on this study, we observed time-dependent decreasing trends for both the serum total glutathione and gsh during the first week of burn trauma. however, an increasing trend was recorded for the serum oxidized glutathione within the first week of injury, which was time-dependent as well. moreover, since the damaged body surface area is one of the factors involved in both the indication of hospitalization and prognosis, we planned to figure 2: correlation of pro-oxidant-antioxidant balance (pab) with total body surface area (tbsa) burnt. investigate the possible correlation between this factor and the above-mentioned redox markers. no significant correlation between serum glutathione level and the tbsa of burn injury was observed in our study. however, pab values showed a significant and direct association with burnt tbsa. the perturbation of redox homeostasis during burn injury has been addressed in a number of studies (4-6, 29, 30). in this study, we could also demonstrate a significant degree of redox perturbation, which was documented as the decreased level of serum total and reduced glutathione as well as gsh/gssg ratio, which were accompanied with increased level of oxidized glutathione. the observed changes were time-dependent, which is supported by the results of szczesny, b. et al (31). however, as observed in this study, the magnitude of increase in serum oxidized glutathione (gssg) was not as big as the decrease of serum glutathione (gsh) concentration. considering this fact, along with decreased level of total serum glutathione, it might be suggested that gsh is probably recruited during burn injury to protect cellular and extracellular proteins from irreversible oxidations such as the formation of sulfinic and sulfonic acid (32) through glutathionylation of these proteins (figure 3) (33, 34). since this posttranslational modification is reversible, proteins can retain their activities after controlling the acute phase of injury (3538). on the other hand, since the administration of ascorbic acid as a part of the routine therapeutic protocol in our hospital was started from the second day of hospitalization, the extent of oxidative damage as a consequence of burn injury could be much more significant if there were not any antioxidants in the drug regimen. the more significant decrease of total glutathione and gsh, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e54 figure 3: possible mechanism and consequences of oxidative stress in burn injury. this schematic figure suggests two pathways of gsh consumption during burn injury including its oxidation to gssg and its application in glutathionylation. as well as the more dramatic decrease in gsh/gssg ratio from the 1st day to 2nd day in comparison to changes from the 2nd day to 7th day could also be explained by the protective effects of ascorbic acid against oxidative damages. in this study, the first sample was taken during the first 6 hours of hospitalization, and the second sample was taken 24 hours later and before the administration of ascorbic acid, which is a part of the routine therapeutic protocol for burn injury in imam reza hospital, mashhad, iran. the third sample was taken on day 7, which means the serum redox status of patients was studied after the administration of a distinguished antioxidant for 6 days and daily administration of ascorbic acid. since the administration of ascorbic acid could not be avoided due to ethical reasons, we could not study the changes of glutathione as well as pab without use of any antioxidant in this group of patients. performing the same study in animal models can be recommended to solve this limitation. there are several studies showing the advantages of antioxidant therapy in management of burn injuries (39). nacetylcysteine is an antioxidant and its effects on oxidative stress have been studied (8, 29). ascorbic acid is another example of antioxidants that is shown to attenuate the oxidative stress (40). in a study by lalonde et a.l, using rats as animal models, oral administration of a mixture containing glutathione, n-acetylcysteine and ascorbic acid showed a protective effect against burn-induced altered cell energetic (6). however, the severity of burn injury was not introduced as a factor for determination of the required dosage of antioxidants in any of these studies. 5. limitation the oxidative stress after burn is supposed to start quickly. therefore, the first sample had to be taken as soon as possible. however, considering the time interval between injury and hospitalization and since our hospital is the referral center for a large area of iran, more we than 6 hours might have passed at from the trauma at the time of admission but decided to take the samples from the patients during the first 6 hours of admission anyway. for other samples, we should have ideally checked our patients on all days of hospitalization; but financially we had limitations, which made us be restricted to the 2nd and 7th days. 6. conclusion according to this study, the redox perturbation in burn injury, which was measured as the pab value positively correlated with the severity of dermal damage, which may suggest that the dosage of antioxidants should be proportionate to the surface area of skin that is damaged. 7. appendix 7.1. acknowledgements we are very grateful to all patients who participated in this study. this work was based on the research project no. 88482, as the msc dissertation of roya askarian, financed by research council of mashhad university of medical sciences. 7.2. author contribution abt, ms and sih contributed to the conception and design of the study. ra, fsh and sih contributed to the acquisition, analysis and interpretation of data. ra, fsh and sih drafted the manuscript; abt, ms and sih revised it critically for content. all authors read and approved the final manuscript submitted for publication. 7.3. funding/support this work was financed by the research council of mashhad university of medical sciences, mashhad, iran. 7.4. conflict of interest authors declare that there is no competing interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. beiraghi-toosi et al. 6 references 1. sheridan rl, ryan cm, yin lm, hurley j, tompkins rg. death in the burn unit: sterile multiple organ failure. burns. 1998;24(4):307-11. 2. brusselaers n, monstrey s, snoeij t, vandijck d, lizy c, hoste e, et al. morbidity and mortality of bloodstream infections in patients with severe burn injury. am j crit care. 2010;19(6):e81-7. 3. ward pa, till go. 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clinical nutrition. 1991;54(6):1119s-24s. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e70 or i g i n a l re s e a rc h baseline characteristics and associated factors of mortality in covid-19 patients; an analysis of 16000 cases in tehran, iran alireza zali1, saeid gholamzadeh2,3, gohar mohammadi2, mehdi azizmohammad looha4, forouzan akrami5, elaheh zarean6, reza vafaee7, ali maher8, mahmood khodadoost9∗ 1. functional neurosurgery research center, shohada tajrish neurosurgical center of excellence, shahid beheshti university of medical sciences, tehran, iran. 2. vice chancellor in administration and resources development affairs, shahid beheshti university of medical sciences, tehran iran. 3. legal medicine research center, legal medicine organization, tehran, iran. 4. cancer research center, shahid beheshti university of medical sciences, tehran, iran. 5. medical ethics and law research center, shahid beheshti university of medical sciences, tehran, iran. 6. modeling in health research center, shahrekord university of medical sciences, shahrekord, iran. 7. proteomics research center, student research committee, shahid beheshti university of medical sciences, tehran, iran. 8. department of health policy, economics and management, school of management and medical education, shahid beheshti university of medical sciences, tehran, iran. 9. school of traditional medicine, traditional medicine & materia medica research center shahid beheshti university of medical sciences, tehran, iran. received: august 2020; accepted: september 2020; published online: 6 september 2020 abstract: introduction: given the importance of evidence-based decision-making, this study aimed to evaluate epidemiological and clinical characteristics as well as associate factors of mortality among admitted covid-19 cases. methods: this multicenter, cross-sectional study was conducted on confirmed and suspected covid-19 cases who were hospitalized in 19 public hospitals affiliated to shahid beheshti university of medical sciences (sbmu), tehran, iran, between february 19 and may 12, 2020. epidemiological and clinical characteristics of the infected cases were compared between the deceased and survivors after discharge. case fatality rates (cfrs) were calculated across all study variables. single and multiple logistic regressions were used to explore the risk factors associated with coivd-19 mortality. results: out of the 16035 cases that referred to the hospitals affiliated to sbmu, 16016 patients (99.93% of confirmed and 99.83% of suspected cases) were hospitalized. 1612 patients died with median hospitalization days of 5 (interquartile range (iqr): 2-9) and 3 (1-7) for confirmed and suspected covid-19 cases, respectively. the highest death rate was observed among ages>65 (63.4% of confirmed cases, 62.3% of suspected cases) and intensive care unit (icu)/critical care unit (ccu) patients (62.7% of confirmed cases, 52.2% of suspected cases). total case fatality rate (cfr) was 10.05% (13.52% and 6.37% among confirmed and suspected cases, respectively). the highest total cfr was observed in patients with age>65 years (25.32%), underlying comorbidities (25.55%), and icu/ccu patients (41.7%). the highest cfr was reported for patients who had diabetes and cardiovascular diseases (38.46%) as underlying non-communicable diseases (ncds), and patients with cancer (35.79%). conclusion: this study showed a high cfr among suspected and confirmed covid-19 cases, and highlighted the main associated risk factors including age, sex, underlying ncds, and icu/ccu admission affecting survival of covid-19 patients. keywords: covid-19; inpatients; survival; mortality; comorbidity; noncommunicable diseases; iran cite this article as: zali a, gholamzadeh s, mohammadi g, azizmohammad looha m, akrami f,zarean e, vafaee r, maher r, khodadoost m. baseline characteristics and associated factors of mortality in covid-19 patients; an analysis of 16000 cases in tehran, iran. arch acad emerg med. 2020; 8(1): e70. ∗corresponding author: mahmood khodadoost; school of traditional medicine, traditional medicine & materia medica research center, shahid beheshti university of medical sciences, tehran, iran. tel: +98 21 22439890, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zali et al. 2 1. introduction the covid-19 pandemic is currently known as an ongoing pandemic of one the most fatal types of infectious diseases [1, 2]. the disease was first reported in wuhan, hubei, china in december 2019. after sars coronavirus (sars-cov ) in 2002 and middle east respiratory syndrome coronavirus (mers-cov ) in 2012, the covid-19 outbreak is recognized as the third outbreak of coronavirus since two decades ago [3]. the pandemic was caused by severe acute respiratory syndrome coron3virus 2 (sars-cov-2) [4] affecting more than 5.5 million people all over the world up to now [5/26/2020]. more than 340,000 of the population infected by covid-19 faced death in all countries [5]. europe and the unites states of america reported the highest incidence and mortality rates of covid-19 among all countries with almost 2 million cases and 168,917 deaths in europe and over 1.7 million patients with covid-19 in the us and around 100,000 deaths in the us [5, 6]. the first confirmed covid-19 case in iran was reported on february 20, 2020, in qom province [7] and until aug 2 2020, a total of 306,752 confirmed covid-19 cases were reported and 16,982 patients had died due to covid-19 in iran [8]. according to the most recently updated global statistics, iran currently ranks 10th in the world and second in the middle east in terms of the number of deaths due to covid-19 [5]. recent studies have found that several risk factors could be associated with an increased risk of death among covid-19 cases, which should be taken into account when it comes to control and management of the pandemic [6, 9, 10]. among these risk factors, pre-existing non-communicable comorbidities such as cancers, diabetes, hypertension, cardiovascular diseases, chronic kidney diseases, chronic pulmonary diseases, and other chronic diseases could be regarded to be the most important risk factors of death in covid-19 patients [9, 11, 12]. therefore, assessing these characteristics could help decision-makers, clinicians, and scholars to decrease the burden of covid-19 disease. at the time of an outbreak of infectious diseases, such as covid-19, case fatality rate (cfr) can help epidemiologists and health care experts to identify abnormalities present in a population and help researchers estimate mortality rates due to the disease early on [13-15]. however, performing this quantification could be hampered by issues such as extent of testing, as lack of an accurate estimation of cfr in the early stages of a pandemic may result in underestimation of mortality rates [14]. nevertheless, employing this indicator could improve the estimation of fatality rate and monitoring email: khodadost.m@gmail.com its general, and help estimate the spread of the infection in a society. based on a recent study conducted in iran, crf had a downward trend until march 26, 2020 [16], but changes in the number of cases since march made substantial changes to this indicator, which should be taken into consideration. exploring the epidemiological features of covid-19 and assessing underlying comorbidities among affected patients could help public health officials, decision makers and clinicians to take initiative in reducing the burden of this infectious disease and consequently control the epidemic. although several studies have been recently performed to report certain epidemiological characteristics of the disease in the us, europe and mainly china [17-22], few studies have assessed these important factors in iranian populations [23-26]. this study aimed to evaluate some of the epidemiological and clinical characteristics as well as associated factors of mortality in a sample of the iranian population, by studying confirmed and suspected cases of covid-19 among all those who were hospitalized in public hospitals and medical centers affiliated to shahid beheshti university of medical sciences (sbmu), tehran, iran. 2. methods 2.1. study design and participants this cross-sectional study was performed in 19 hospitals in tehran, iran, which were designated as covid-19 medical centers, including akhtar, ayatollah ashrafi esfahani, imam hossein, 15 khordad, zaeem, shahid sattari, sevome-shaban, shohadaye pakdasht, shohadaye tajrish, shohadaye gomnam, ayatollah taleghani, torfeh, imam khomeini (firoozkooh), loghman hakim, shahid modarres, masih daneshvari, shahid mofateh(varamin), mofid children’s, and mahdieh. all the mentioned hospitals are affiliated to sbmu and are responsible for 52% of health care services in tehran province. all patients with positive polymerase chain reaction (pcr) test results admitted and hospitalized as confirmed covid-19 cases between february 19 and may 12, 2020 were studied. in addition to laboratory-confirmed sars-cov-2 cases, patients with clinical sings of covid-19 on chest computed tomography (ct) scan findings (presence of ground-glass opacity pattern, consolidation, reticular pattern, or mixed pattern and honeycomb pattern) who initially had negative pcr test results were diagnosed as highly suspected covid-19 patients and hospitalized. the study was approved by research ethics committee of sbmu, tehran, iran (ir.sbmu.retech.rec.1399.486). 2.2. definitions survival time was defined as the time interval between hospital admission and discharge (survived or deceased). surthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e70 vivors were defined as patients who were alive at the time of discharge from the hospital. cfr, also called case fatality rate or case fatality ratio, in epidemiology, is the proportion of people who die from a specified disease among all individuals diagnosed with the disease over a certain period of time. in this study, case fatality rate was calculated by dividing the number of deaths from covid-19 disease over a defined period of time by the number of individuals diagnosed with the disease during that time (pcr &ct). the deceased cases were patients who died due to covid-19 during the study period [27]. 2.3. data collection and preparation the epidemiological and demographic data were extracted from hospital intelligent management (him) system. him system is a comprehensive and integrated decision-making system. in this system, hospital performance information is integrated from various databases, and then it is provided to managers in the form of performance reports and specialized dashboards. the information extracted, from both the laboratory-confirmed sars-cov-2 and suspected cases, included underlying comorbidities, laboratory and radiological findings, treatment and death outcome during hospitalization and recovery status (complete or partial), which are displayed in the him system. data quality control was performed in several steps. duplicate records were identified based on patients’ national identification code. for patients without a national code in the him system, first name and surname, admission code, patient’s address, age, and other registered information were checked. patients with the same information in all mentioned characteristics were identified as a duplicate record and removed from the dataset. if the patient was admitted at different times, the first date of referral was considered as the first time of infection. patients who had records as both confirmed and suspicious case, their confirmed status was considered as the final diagnosis. any missing or unknown records in the him system were collected and clarified through checking the hospital medical records units, and asking from patients and their families. 2.4. statistical analysis frequency (percentage) was reported for all categorical variables in survivors, the deceased, and total cases. continuous variables with symmetric and skewed distribution were described as mean (standard deviation (sd)) and median (first quantile-third quantile). chi-square, independent test, and fisher’s exact test were used to determine if there is a significant relationship between categorical variables and status (deceased or survivor). independent t-test and mannwhitney u test were used to compare the mean and median of continuous variables between survivors and deceased cases, respectively. cfrs were calculated for categorical variables based on status. the unadjusted and adjusted cox proportional-hazard models were applied to determine the impact of variables on the survival time of cases and results were reported using hazard ratio (hr) and 95% confidence interval (ci). statistical analyses were done using ibm spss version 26 and p-value less than 0.05 was considered as statistically significant. 3. results 3.1. baseline characteristics of studied cases from february 19, 2020 to may 12, 2020, 8252 confirmed covid-19 cases and 7783 individuals diagnosed as suspected cases of covid-19 had referred to hospitals affiliated to sbmu, iran, tehran. results showed that 8246 (99.93%) of the confirmed cases and 7770 (99.83%) of the suspected cases had been hospitalized and the rest had received outpatient health care services. figure 1 shows the distribution of daily new cases of covid-19 during the study period. evaluation of all inpatients revealed that 1116 (13.52%) of confirmed and 506 (6.37%) of suspected covid-19 cases, had died during 5 (iqr=2-9) and 3 (iqr=1-7) days of hospitalization, respectively. the age of patients significantly correlated with survival status in both confirmed and suspected cases (p < 0.001). the mean (sd) age of confirmed covid19 patients who died was 67.54 (15.81) years, while this value was 49.17 (17.43) years for recovered cases. in addition, suspected cases who died due to covid-19 had the mean age of 66.65 (19.52) while mean age of the suspected survivors was 47.65 (18.99) years. most of the new cases (57.2% of confirmed cases and 56.9% of suspected cases) and patients who died from covid-19 (63.4% of confirmed cases and 59.5% of suspected cases) were male in our study (table 1). 3.2. case fatality rate the overall cfr was 10.05%, while the rate was 13.52% and 6.37% for confirmed and suspected cases of covid-19, respectively. seniors had higher cfr compared to other age categories with 32.49% for confirmed and 16.82% for suspected cases of covid-19. cfr was reported to be 34.19% among confirmed cases of covid-19 with underlying comorbidities, which was about 3 times higher than those without any comorbidity. the highest cfrs reported among confirmed covid-19 cases belonged to patients with diabetes and cardiovascular diseases (66.67%), unspecified incurable disease (54.55), and cancers (46.43%). however, cfrs among suspected cases of covid-19 with unspecified incurable disease (71.43%), diabetes and hypertension (26.83%) and cancers (20.51%) were higher than those in other groups of underlying morbidities. patients with confirmed covid-19 adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zali et al. 4 mitted to icu/ccu had a cfr of 59.68%, whereas this rate was 22.29% among suspected patients in the icu/ccu (table 2). 3.3. associated factors of mortality survival status was associated with age group (p < 0.001), sex (p < 0.001; only for confirmed covid-19 cases), underlying comorbidities (p < 0.001), type of hospital admission (p < 0.001), and hospital unit (p< 0.001). 22.7% of confirmed cases and 14.7% of suspected cases who died from covid-19 had underlying comorbidities. overall, the most frequent comorbidities were diabetes mellitus (2.5% among confirmed cases; 1.5% among suspected cases) and cardiovascular disease (2.4% of confirmed cases; 1.5% of suspected cases), both of which had a high prevalence among deceased patients. the highest percentage of death due to covid-19 was found in icu/ccu patients with 62.7% of confirmed cases and 52.2% of suspected cases (table 1). figure 2 indicates that the highest number of new covid-19 cases were found in the group of adults (25-64 years old) since the beginning of the outbreak, while the highest frequency of death was reported in seniors (>64 years old). the results of multiple cox proportional hazard regression analysis revealed that being male (adjusted hr: 1.19; 95%ci: 1.05-1.35), age≥65 (adjusted hr: 2.18; 95%ci: 1.93-2.48), and admission to icu/ccu wards (adjusted hr: 3.93; 95%ci: 3.46-4.57) were significant risk factors associated with survival time of confirmed cases who died due to covid-19 during hospitalization. the significant risk factors associated with survival time of deceased suspected cases of covid-19 were age≥65 (adjusted hr: 2.38; 95%ci: 1.97-2.87), underlying comorbidities (adjusted hr: 0.58; 95%ci: 0.75-0.75) and admission to icu/ccu wards (adjusted hr: 3.52; 95% ci:2.94-4.22; table 3). 4. discussion to make decisions on interventions and regulations for controlling covid-19 pandemic, an accurate estimation of epidemiologic rates is required, especially infection and death rates and associated comorbidities. here, by integrating data from nineteen hospitals, we found that almost half of the patients were considered as suspected covid-19 cases and others were confirmed cases who were positive for sars-cov2 in pcr. in addition, our study showed that the peak of covid-19 outbreak occurred in a one-month interval between march 4th and april 4th, 2020. in addition, age, sex, underlying comorbidity, hospitalization in the icu/ccu, and duration of hospitalization were shown to be significant associated risk factors. survival analysis was performed to evaluate the effect of risk factors on death outcome during hospitalization. in both confirmed and suspected groups, risk factors including old age, underlying disease, icu/ccu admission, and duration of hospitalization were significantly associated with patient status (deceased vs. survivors) while sex was associated only with confirmed covid-19. in recent studies, age>60 years has been identified as a major risk factor [2831]. moreover, studies have shown that risk of dying from covid-19 in men is higher than women [28, 31-33]. the relationship between having at least one underlying comorbidity and death rate was also investigated and confirmed [28, 31-35]. the national epidemiologic reports indicate an association between death rate and both age>60 years and having at least one underlying comorbidity [36, 37]. li et al. also showed that a longer duration of hospitalization was associated with a higher risk of death [28]. our findings showed that although about 70% of suspected and confirmed covid-19 cases were in the age of 25-64 years, about 60% of deaths occurred in patients over 65 years old. in addition, approximately 50% of all deaths occurred in icu/ccus patients. according to our results, almost half of the underlying non-communicable diseases (ncds) and related deaths were related to diabetes mellitus and cardiovascular diseases. in a study conducted by hongdou et al. on 5139 infected patients, although 80% of patients were 25-64 years old, approximately 60% of deaths occurred in those aged more than 64 years [38]. similar results were reported in zhonghua et al. study, which included 72314 covid-19 patients [39]. few studies with large sample size have reported death rates due to covid-19 in icu patients. in a study carried out in the united states evaluating the patients records in 12 hospitals, 50% of deaths had occurred in the icus [40]. in a systematic review, the average cfr reported for patients admitted to icu was 25.7% during hospitalization [41]. similar to the findings of our study, cancer, diabetes, hypertension, and cardiovascular diseases were the most common underlying comorbidities among covid-19 cases in various studies [10, 19-21]. in guan et al.’s study, about 70% of patients had diabetes and more than 50% of all deaths were reported among diabetic patients [34]. in our study, cfr was 13.52% among confirmed covid-19 cases, which is almost twice as high as in suspected cases. according to a national study, the cumulative risk for inhospital mortality in 30 days was 24.4% [42]. the cfr in confirmed cases of our study was about 10% higher than that reported by the study of chinese center for disease control and prevention with 2.3% (36). but according to data from the new york city department of health and mental hygiene in may 12, 2020, the cfr in confirmed cases in new york, the most populous city in the united states, was 6.8% [43]. one reason for this difference in results might be that cfr has been calculated among hospitalized patients in our study, while other studies considered all patients, either this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e70 hospitalized or not. cfr indicates the lethality of the disease and only includes the ratio of deaths to patients, and is especially used in acute infectious diseases. cfr may be different in different epidemics because there are changes in the pathogen, host, and environment. cfr is closely related to the virulence of the pathogen. given the mutations and changes in the coronavirus and the higher cfr in patients with underlying ncds, we highly recommend preventing precautions and screening people with underlying diseases with a focus on ncds. we also used unadjusted and adjusted cox proportional hazard for exploring factors associated to covid-19 deaths. our findings showed that male sex, age 65 years or older, and icu/ccu admission were risk factors of the survival of covid-19 patients. in addition, confirmed covid-19 patients had a significantly higher risk of death compared to suspected cases. few studies have reported the risk factors for survival of covid-19 patients. in a study by li et al., male sex and age group of 65 years or older had a significant negative effect on the survival of covid-19 [25]. wang et al. studied 538 confirmed cases of covid-19 and showed that older age was associated with an increase in hospitalization [44]. unfortunately, no study was performed to compare the survival rate between confirmed and suspected covid-19 cases. there are no clear reasons for the higher risk of death among confirmed covid-19 cases compared to suspected ones. cases who were confirmed could have shown more severe symptoms of the disease and were, therefore, more likely to experience death. according to the findings, we highly recommend screening people with underlying ncds in the second phase of the epidemics in order to reduce death rates through early detection and provision of proper care. we also suggest adopting a response plan to manage underlying ncds in the context of covid-19 epidemic. given the high cfr found in this study and the unknown behavior of coronavirus, there is room for more discussions and more data are required. 5. limitations this study was the largest multicenter study ever conducted in tehran province, iran, on patients with covid-19, evaluating the two groups of suspected and confirmed cases of covid-19. however, our data was limited to the public hospitals affiliated to sbmu. 6. conclusion this study showed the high cfr for confirmed covid-19 cases and the difference in cfrs of suspected and confirmed cases. it also highlighted age, sex, underlying ncds, icu/ccu admission, and confirmed/suspected status as associated risk factors of mortality among covid-19 patients. 7. declarations 7.1. acknowledgements the authors appreciate all frontline health workers, health defenders and members of the corona outbreak management committee of tehran province, who sacrificed themselves in the event of covid-19 outbreak. 7.2. author contribution a.z and m.kh and s.gh conceived and designed the research. g.m. and m.a.l. analyzed the data. f.a. and m.a.l and e.z and r.v and a.m interpreted the results and wrote the paper. a.z and m.kh and s.gh edited the paper critically. g.m and f.a. and m.a.l revised the paper. authors orcids alireza zali: 0000-0002-2298-2290 saeid gholamzadeh: 0000-0003-2420-9098 gohar mohammadi: 0000-0002-9512-5652 mehdi azizmohammad looha: 0000-0002-0700-1431 forouzan akram: 0000-0002-5001-0085 elaheh zarean: 0000-0002-2227-8949 reza vafaee: 0000-0003-0677-4755 ali maher: 0000-0002-0448-284x mahmood khodadoost: 0000-0002-6525-0639 7.3. funding/support none. 7.4. conflict of interest the authors have no conflicts of interest. references 1. cucinotta, d. and m. vanelli, who declares covid-19 a pandemic. acta bio-medica: atenei parmensis, 2020. 91(1): p. 157-160. 2. organization, w.h. who director-general’s opening remarks at the media briefing on covid-19 11 march 2020. march 11, 2020]; available from: https://www.who.int/dg/speeches/detail/who-directorgeneral-s-opening-remarks-at-the-media-briefing-oncovid-19—11-march-2020. 3. khachfe, h.h., et al., an epidemiological study on covid-19: a rapidly spreading disease. 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323(20): p. 2052-2059. 41. cases-hospitalizations-deaths. covid-19: data summary nyc health. 2020 [accessed june 9]]; available from: https://www1.nyc.gov/site/doh/covid/covid19-data.page. 42. jalili, m., et al., characteristics and mortality of hospitalized patients with covid-19 in iran: a national retrospective cohort study. annals of internal medicine, 2020. 43. quah, p., a. li, and j. phua, mortality rates of patients with covid-19 in the intensive care unit: a systematic review of the emerging literature. critical care (london, england), 2020. 24(1): p. 285-285. 44. wang, z., et al., survival analysis of hospital length of stay of novel coronavirus (covid-19) pneumonia patients in sichuan, china. medrxiv, 2020: p. 2020.04.07.20057299. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zali et al. 8 table 1: epidemiological, demographic and clinical characteristics of inpatient confirmed and suspected covid-19 variables confirmed cases suspected cases survivors n=7136 deceased n=1116 p survivors n=7287 deceased n=496 p age, years mean (sd) 49.17 (17.43) 67.54 (15.81) <0.001 47.66 (18.99) 66.65 (19.52) <0.001 median (range) 48.00 (0-99) 70.00 (3-97) <0.001 46.00 (0-105) 71.00 (0-102) <0.001 children (0-14) 73/7136 (1.0) 5/1116 (0.4) <0.001 170/7287 (2.3) 14/496 (2.8) <0.001 youth (15-24) 356/7136 (5.0) 10/1116 (0.9) 488/7287 (6.7) 7/496 (1.4) adults (25-64) 5238/7136 (73.4) 394/1116 (35.3) 5101/7287 70.0) 166/496 (33.5) seniors (>65) 1469/7136 (20.6) 707/1116 (63.4) 1528/7287 21.0) 309/496 (62.3) sex <0.001 0.228 male 4010/7136 (56.2) 708/1116 (63.4) 4132/7287(56.7) 295/496 (59.5) female 3126/7136 (43.8) 408/1116 (36.6) 3155/7287 (43.3) 201/496 (40.5) underlying comorbidity <0.001 <0.001 yes 487/7136 (6.8) 253/1116 (22.7) 463/7287 (6.4) 73/496 (14.7) no 6649/7136 (93.2) 863/1116 (77.3) 6824/7287 (93.6) 423/496 (85.3) underlying comorbidity (type) <0.001 <0.001 no disease history 6649/7136 (93.2) 863/1116 (77.3) 6824/7287 (93.6) 423/496 (85.3) diabetes mellitus (dm) 155/7136 (2.2) 53/1116 (4.7) 104/7287 (1.4) 13/496 (2.6) cardiovascular disease 130/7136 (1.8) 66/1116 (5.9) 99/7287 (1.4) 17/496 (3.4) pulmonary disease 44/7136 (0.6) 31/1116 (2.8) 73/7287 (1.0) 4/496 (0.8) hypertension (htn) 47/7136 (0.7) 25/1116 (2.2) 61/7287 (0.8) 9/496 (1.8) cancer 30/7136 (0.4) 26/1116 (2.3) 31/7287 (0.4) 8/496 (1.6) dm and htn 32/7136 (0.4) 18/1116 (1.6) 30/7287 (0.4) 11/496 (2.2) neurological disease 16/7136 (0.2) 12/1116 (1.1) 15/7287 (0.2) 4/496 (0.8) kidney disease 12/7136 (0.2) 1/1116 (0.1) 28/7287 (0.4) 1/496 (0.2) unspecified incurable 5/7136 (0.1) 6/1116 (0.5) 2/7287 (0.0) 5/496 (1.0) dm and cardiovascular 2/7136 (0.0) 4/1116 (0.4) 6/7287 (0.1) 1/496 (0.2) anemia 3/7136 (0.0) 2/1116 (0.2) 5/7287 (0.1) 0/496 (0.0) others* 11/7136 (0.2) 9/1116 (0.8) 9/7287 (0.1) 0/496 (0.0) pregnancy 0.349 1.000 yes 7/7136 (0.1) 2/1116 (0.2) 6/7287 (0.1) 0/496 (0.0) no 7129/7136 (99.9) 1114/1116(99.8) 7281/7287 (99.9) 496/496(100.0) type of hospital admission <0.001 <0.001 hospitalization 3967/7136 (55.6) 1043/1116 (93.5) 2957/7287 (40.6) 434/496 (87.5) temporary 3163/7136 (44.3) 73/1116 (6.5) 4317/7287 (59.2) 62/496 (12.5) outpatient 6/7136 (0.1) 0/1116 (0.0) 13/7287 (0.2) 0/496 (0.0) wards <0.001 <0.001 icu and ccu 473/7136 (6.6) 700/1116 (62.7) 903/7287 (12.4) 259/496 (52.2) others 6663/7136 (93.4) 416/1116 (37.3) 6384/7287 (87.6) 237/496 (47.8) duration of hospitalization (days) median (q1-q3) 1 (0-5) 5 (2-9) <0.001 0 (0-2) 3 (1-7) <0.001 data are expressed as mean (standard deviation), median (q1-q3) and frequency (percentage) for symmetric numeric variables, asymmetric numeric variables and categorical variables, respectively. p-values are used for comparing mean or median of numeric variables between survivors and deceased patients using independent t-test and mann-whitney u test. the p-values for categorical variable are for assessing the independence assumption between patients’ status (survivors versus deceased) and categorical variables. * others group in underlying comorbidities included aids, autoimmune disorders, gastrointestinal disease, war injuries, tuberculosis, thyroid disease, and hepatitis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 9 archives of academic emergency medicine. 2020; 8(1): e70 table 2: case fatality rate of patients hospitalized due to covid-19 variables all cases n=16035 confirmed n=7287 suspected n=496 age, years children (0-14) 7.25 6.41 7.61 youth (15-24) 1.97 2.73 1.41 adults (25-64) 5.14 7.00 3.15 seniors (>65) 25.32 32.49 16.82 sex male 10.97 15.01 6.66 female 8.84 11.54 5.99 underlying comorbidity yes 25.55 34.19 13.62 no 8.71 11.49 5.84 underlying comorbidity (type) no disease history 8.71 11.49 5.84 diabetes mellitus (dm) 20.31 25.48 11.11 cardiovascular disease 26.60 33.67 14.66 pulmonary disease 23.03 41.33 5.19 hypertension 23.94 34.72 12.86 cancer 35.79 46.43 20.51 dm and hypertension 31.87 36.00 26.83 neurologic disease 34.04 42.86 21.05 kidney disease 4.76 7.69 3.45 unspecified incurable 61.11 54.55 71.43 dm and cardiovascular 38.46 66.67 14.29 anemia 20.00 40.00 0.00 others* 31.03 45.00 0.00 pregnancy yes 13.33 22.22 0.00 no 10.05 13.51 6.38 type of hospital admission hospitalization 17.58 20.82 12.80 temporary 1.77 2.26 1.42 outpatient 0.00 0.00 0.00 hospital unit ccu/icu 41.07 59.68 22.29 others 4.77 5.88 3.58 total % 10.05 13.52 6.37 * others group in underlying comorbidities included aids, autoimmune disorders, gastrointestinal disease, war injuries, tuberculosis, thyroid disease and hepatitis. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zali et al. 10 table 3: unadjusted and adjusted cox proportional hazards regression model for death during hospitalization group variable unadjusted hazard adjusted hazard hr 95% cis p value hr 95% ci p value sex male vs. female 1.23 1.09-1.39 0.001 1.19 1.05-1.35 0.005 age, ≥65 years vs. <65 years 2.78 2.46-3.14 <0.001 2.18 1.93-2.48 <0.001 confirmed case underlying, yes vs. no 1.20 1.04-1.39 0.003 0.90 0.78-1.03 0.895 hospital wards, icu/ccu vs. others 4.57 4.04-5.17 <0.001 3.93 3.46-4.57 <0.001 pregnancy, yes vs. no 0.57 0.17-2.73 0.381 — — — sex, male vs. female 1.15 0.96-1.38 0.120 — — — age, ≥65 years vs. <65 years 2.69 2.23-3.24 <0.001 2.38 1.97-2.87 <0.001 underlying, suspected cases yes vs. no 0.70 0.54-0.90 0.006 0.58 0.45-0.75 <0.001 hospital wards, icu/ccu vs. others 3.90 3.26-4.67 <0.001 3.52 2.94-4.22 <0.001 pregnancy, yes vs. no — — — — — — sex, male vs. female 1.22 1.10-1.35 <0.001 1.22 1.11-1.35 <0.001 age, ≥65 years vs. <65 years 2.71 2.45-3.01 <0.001 2.21 1.99-2.45 <0.001 underlying, all patients yes vs. no 1.03 0.91-1.16 0.682 — — — hospital wards, icu/ccu vs. others 4.36 3.95-4.84 <0.001 3.75 3.37-4.16 <0.001 pregnancy, yes vs. no 0.60 0.15-2.40 0.468 — — — covid-19 status, confirmed vs suspected 1.21 1.09-1.357 <0.001 1.13 1.02-1.26 0.022 ci: confidence interval; hr: hazard ratio. * all significant variables in the unadjusted model were included in the adjusted model. other variables were removed from the adjusted model. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 11 archives of academic emergency medicine. 2020; 8(1): e70 figure 1: the distribution of daily new admitted cases of covid-19 from february to may 2020 in hospitals affiliated to shahid beheshti university of medical sciences, tehran, iran. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem a. zali et al. 12 figure 2: the distribution of a) number of new cases, and b) number of deaths based on age group and time periods among covid-19 cases admitted to hospitals affiliated to shahid beheshti university of medical sciences, tehran, iran, from february to may 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2018; 6 (1): e37 or i g i n a l re s e a rc h examination of references in rosen’s emergency medicine text book, 8t h edition; an observational study ramazan güven1 ∗ 1. department of emergency medicine, bitlis state hospital, bitlis, turkey. received: february 2018; accepted: june 2018; published online: 16 june 2018 abstract: introduction: this study aims to analyze the references that the authors and editors used during the writing of rosen’s emergency medicine, 8th edition. methods: 15,209 references, which were used in 197 chapters of rosen’s emergency medicine, 8th edition, were examined regarding the distribution of countries, journals, publication year, and the department of the affiliation of the first author. results: a total of 63.1% (n = 9591) of the references were led by authors from the united states (us). us-based journals were mostly used, and annals of emergency medicine was the journal from which the references were most frequently extracted, with a percentage of 5.2% (n = 756). the studies conducted by emergency physicians have increased in recent years, and emergency physicians, with a percentage of 17.8% (n = 351), were the leading authors of studies conducted between 2010 and 2013, which were cited in the references of rosen’s emergency medicine, 8th edition. conclusion: us-based studies make up a significantly bigger portion of the references used in rosen’s emergency medicine, 8th edition. if europe and other countries give due importance to emergency medicine, they will have the capability to produce studies that can be used as references in textbooks as much as the us. keywords: emergency medicine; reference books; europe; publications; united states; writing © copyright (2018) shahid beheshti university of medical sciences cite this article as: güven r. examination of references in rosen’s emergency medicine text book, 8t h edition; an observational study. 2018; 6(1): e37. 1. introduction emergency medicine, which first took root in the united states approximately 50 years ago, has experienced rapid growth since it first started (1). emergency medicine residency programs first started at the university of cincinnati in 1970 (2). as of 2016, 33,510 emergency physicians have been certified by the emergency physicians american board of emergency medicine (abem) in the united states. at present, the emergency medicine specialty is being accepted as an area of specialization in more than 60 countries (4, 5). one of the most important reference guides for emergency physicians is rosen’s emergency medicine; its first edition was published in 1983 under the leadership of peter rosen, who was the founding editor. rosen’s emergency medicine is one of the most comprehensive textbooks of emergency medicine, and it is in the top rank of key textbooks that are ∗corresponding author: ramazan güven; emergency medicine, bitlis state hospital, bitlis, turkey. tel: +905323341721, email: ramon.ra.dr@gmail. com. most recommended by many emergency medicine academicians (7). rosen’s emergency medicine, 8th edition, which was awarded the medical book award by the british medical association (bma) in 2014, was highly commended by the same organization. one of the most important parts of the writing phase of a textbook is the collection of literature references (8). the authors should select the references they use carefully to support their arguments and provide reliability. during the writing phase, the authors of key textbooks select with caution the references and publications they prefer; such references are directly related to the quality of the book. we think that the countries where these studies were conducted recognized emergency medicine as a specialty and also attached importance to the improvement of emergency medicine clinics. in line with this hypothesis, in the current study, we aimed to examine the references that the authors and editors used when writing the eighth edition of rosen’s emergency medicine. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com ramon.ra.dr@gmail.com ramon.ra.dr@gmail.com r. güven 2 table 1: distribution of references of rosen’s emergency medicine, 8th edition, based on countries country number (%) em# country number (%) em# usa 9591 (63.1) yes greece 65 (0.4) no uk 912 (6.0) yes taiwan 62 (0.4) yes canada 654 (4.3) yes india 59 (0.4) yes germany 311 (2.0) no south korea 55 (0.4) yes australia 303 (1.9) yes denmark 55 (0.4) yes france 267 (1.8) yes austria 54 (0.4) no italy 248 (1.6) yes brazil 53 (0.3) no holland 246 (1.6) yes south africa 44 (0.3) yes israel 156 (1.0) yes ireland 41 (0.3) yes switzerland 154 (1.0) no singapore 41 (0.3) yes japan 146 (0.9) yes new zealand 34 (0.2) yes spain 111 (0.7) yes malaysia 30 (0.2) yes turkey 110 (0.7) yes iran 28 (0.2) yes sweden 97 (0.6) yes saudi arabia 26 (0.2) yes china 90 (0.6) yes poland 25 (0.2) yes finland 71 (0.5) yes scotland 24 (0.2) yes belgium 70 (0.5) yes thailand 24 (0.2) yes norway 66 (0.4) no others* 886 (5.8) yes *references other than journals (books, reports, etc.) or references from an unknown country of the first author or from other countries; # is emergency medicine a recognized specialty? table 2: distribution of references in rosen’s emergency medicine, 8th edition, based on publication years year of publication department n (%) emergency other total 2010–2013 351 (17.8) 1623 (82.2) 1974 (13.6) 2005–2009 798 (15.2) 4440 (84.8) 5238 (36.2) 2000–2004 560 (15. 0) 3182 (85.0) 3742 (25.9) 1995–1999 263 (16.1) 1366 (83.9) 1629 (11.2) 1990–1994 138 (15.3) 765 (84.7) 903 (6.3) 1985–1989 71 (13.7) 448 (86.3) 519 (3.6) 1980–1984 21 (9.5) 200 (90.5) 221 (1.5) ≤1979 4 (1.9) 204 (98.1) 208 (1.4) 2. methods: 2.1. study design and settings this observational study was conducted between jan 08, 2016 and jan 08, 2017 to analyze the references of rosen’s emergency medicine, 8th edition regarding the distribution of countries, journals, publication year and affiliation of the first authors. 2.2. data gathering the references used in all chapters of rosen’s emergency medicine, 8th edition, were collected. the databases of pubmed, scopus, researchgate, scimago journal & country rank, and google scholar and online libraries of universities were checked to access the bibliography of the references. the country and the department in which the first author was working during the publication of the study, the publication year of the reference, and the type of publication (i.e., journals and books), were extracted for all references. the number of references used in each five year period, and the ratios of these references in emergency department and in other departments were also investigated. this study was conducted by an independent researcher who was blinded to our hypothesis in order to prevent bias. furthermore, another independent researcher assessed all references for citation and quotation accuracy. despite all these efforts, the first authors of some studies, primarily old ones, could not be found or the countries where some studies were conducted could not be identified. therefore, these studies were indicated as “others” in the main text and tables. studies cited in the eighth edition of rosen’s emergency medicine were from more than two hundred different journals and over fifty countries. information about emergency service in those countries (whether emergency medicine is recognized as a specialty or not) was obtained from the american journal of emergency physicians (acep), european society for emergency medicine (eusem) and official websites of the ministries of health in the respective countries as well this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e37 as websites of their emergency medicine societies, if any. the ranking of the countries and journals was obtained from “scimagojr.com”. 2.3. statistical analysis spss 22.0 (armonk, ny: ibm corp.) was used for analysis of these data and simple destriptive statistics was used to record numbers and percentages. 3. results: 15,209 references were cited in 197 chapters. 14,437 (94.9%) of the used references were taken from journals, and 772 (5.1%) of the references were taken from other sources (books, guidelines, reports, etc.). 3.1. country distribution of references with regard to the country of the first authors, the us was found to be the most common country (63.1% of first authors, n = 9591), followed by the united kingdom (uk) (6.0% first authors, n = 912) and canada (4.3% of first authors, n = 654) (table 1). 3.2. journal distribution of references the journals that were used as references most frequently were annals of emergency medicine (5.2%, n = 756), new england journal of medicine (4.2%, n = 614), journal of trauma and acute care surgery (2.9%, n = 431), journal of the american medical association ( jama) (2.6%, n = 384), academic emergency medicine (2.5%, n = 431), and the american journal of emergency medicine (ajem) (2.3%, n = 337) (figure 1). 3.3. department distribution of references when the departments of the first authors of the references were examined, the most common department was emergency department (14.5%, n = 2206), followed by department of medicine (11.6%, n = 1766). it was found that 86.5% (n = 1905) of emergency physicians included as the first author in the references were from the us and canada (figure 2). 3.4. publication year distribution of references it was found that the studies published between 2005 and 2009 were most frequently used (35.8%, n = 5238). when references that listed emergency physicians as the first authors were examined, the ratio of emergency physicians to other physicians had increased in recent years, and this ratio was 17.8% (n = 351) in the last 4 years (2010–2013) (table 2). 4. discussion: emergency physicians diagnose patients admitted to the emergency department and treat them with the information they obtain from key textbooks such as rosen’s emergency medicine. a key textbook passes many stages of writing and includes the contribution of many authors. rosen’s emergency medicine, 8th edition, was written over a long period of 4 years and, during this period, many important references were used for citations in the book (6). when the data obtained from the scopus-scimago journal & country rank (ssjr) were examined, it was found that out of the 9,917 studies in the field of emergency medicine that were published in 2016, 33.0% (n = 3273) were performed by authors from the us, 9.1% (n = 904) were performed by authors from germany, and 5.1% (n = 510) were performed by authors from the uk (9). the analysis of the references of rosen’s emergency medicine, 8th edition revealed that studies by authors from the us and canada were used the most, and the studies by the authors from europe and other countries lagged behind. moreover, with regard to the ratio of the studies by emergency physicians used as references, it was found that the emergency physicians from europe were much behind those from the us and canada in terms of conducting and publishing studies in emergency medicine. this could be related to the fact that the emergency medicine clinic is not yet at the desired level in europe; for instance, emergency medicine is not yet known as a field of specialization in germany. it is necessary to accept emergency medicine as a field of specialization and to increase the academic opportunities for emergency physicians in europe and other countries to enable them to contribute to this field. another subject that was addressed in the current study was the studies published in which journals were cited most as references in rosen’s emergency medicine, 8th edition. according to the s-sjr 2016 data (10), when the h-index score in the field of emergency medicine and the countries in which they were published were analyzed, it was found that the h-index score was the highest for annals of emergency medicine (us, h-index score = 130); other scores were resuscitation (european, h-index score = 109), academic emergency medicine (us, h-index score = 101), shock (us, h-index score = 101), injury (european, h-index score = 96), burns (us, h-index score = 80), american journal of emergency medicine (us, h-index score = 80), journal of emergency medicine (h-index score = 64), and emergency medicine journal (european, h-index score = 63). the analysis of the journals whose articles were cited in rosen’s emergency medicine, 8th edition revealed a similar result, that is, the most common journal was ann emerg med; moreover, almost all of the first 10 journals with most cited references were us-based journals. tsai et al. also reported a similar finding in their studies in which they examined the most frequently cited references in emergency medicine. they reported that the most frequently cited references were pubthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. güven 4 figure 1: distribution of references in rosen’s emergency medicine, 8th edition, based on journals. lished mainly in the journals originating from the us including annals of emergency medicine (10). therefore, this result can be interpreted as the studies published in the us-based journals are the leading academic contributors to the field of emergency medicine. the ratio of the studies in the field of emergency medicine to total studies in the field of medicine was compared with the data obtained from s-sjr. out of the 341,316 studies performed in 1996, 0.71% (n = 2455) were in the field of emergency medicine. out of the 12,201,133 studies performed in the field of medicine between 1996 and 2016, 0.95% (n = 116,488) were in the field of emergency medicine. out of the 912,801 studies performed in the field of medicine in 2016, 1.08% were related to emergency medicine. furthermore, although only 53 countries made contributions to the studies in the field of emergency medicine in 1996, this number increased to 134 countries in 2016 (9, 11, 12). analysis of the publication dates of the references in rosen’s emergency medicine, 8th edition, based on years showed that the rate of emergency physicians leading the studies has gradually increased, and it was highest between 2010 and 2013. in light of the data obtained from s-sjr and information obtained from the references in rosen’s emergency medicine, 8th edition, it was observed that contributions by emergency physicians in the field of medicine have gradually increased. similar results were obtained in the study by liang y et al. (13), in which the development of emergency medicine was investigated via evaluation of impact factors of 24 emergency journals. according to this previous study, the impact factors of journals of emergency medicine have increased from 2005 to 2014. contributions of emergency physicians to medical literature are increasing. however, the number of the studies this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6 (1): e37 figure 2: distribution of references in rosen’s emergency medicine, 8th edition, based on departments. conducted in emergency fields in countries other than the us increased gradually, which was not so remarkable (14, 15). li q et al. examined all the studies published from 2006 to 2010 in 13 most commonly cited emergency medicine journals. li q et al. reported that the studies originating from the us accounted for 46.3%, which were also among the most commonly cited studies (16). this is consistent with our findings. 5. limitations there are a few limitations in this study. first, references of a key textbook in emergency medicine from european or countries other than the us were not examined in addition to rosen’s emergency medicine, 8th edition. the editors of rosen’s emergency medicine, 8th edition, are physicians from the us. this might be the reason why they mainly had access to the studies conducted in their own country and were influenced by such studies. another limitation is that the editors ignored the publications inthe field of emergency medicine in languages other than english. since there are some publications that were written in english but could not provide important contributions to emergency medicine, maybe the editors did not prefer these studies in languages other than english as references. 6. conclusion: based on the findings, the studies were mostly performed by authors from the us and that us-based journals were mostly used for citing references. although the rate of using the studies performed by emergency physicians as a reference has gradually increased, countries other than the us are not at a desirable level of contribution to the field of emergency medicine. 7. appendix 7.1. acknowledgements i would like to thank all the editors and authors especially peter rosen for providing this valuable book to emergency medicine. also, i would like to thank zubeyir dalgic and gokhan eyupoglu for contributing to this study as cothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com r. güven 6 workers. 7.2. authors contributions the study was designed by ramazan güven. references were searched on the internet and uploaded to spss by ramazan güven. professional support was obtained for the statistical analysis and data analysis and management. ramazan güven wrote the first draft and others revised the manuscript critically. statistics team and ramazan güven approved the final version of the manuscript to be published and are accountable for all aspects of the work. 7.3. funding support none. 7.4. ethical approval not needed. 7.5. conflict of interest the authors declare no conflict of interest in relation to this work. references 1. suter re. emergency medicine in the united states: a systemic review. world journal of emergency medicine. 2012;3(1):5. 2. williams rm. the costs of visits to emergency departments. new england journal of medicine. 1996;334(10):642-6. 3. zink bj. anyone, anything, anytime: a history of emergency medicine: elsevier health sciences; 2006. 4. acep.org. international reports by country//acep. 2017. available from:https://www.acep.org/iscontent.aspx?id=31034& formdataid=13719#sm.001rkwl5zusycq811131b2m549x8f 5. totten v, bellou a. development of emergency medicine in europe. academic emergency medicine. 2013;20(5):514-21. 6. rosen p. marx ja hr, walls rm, biros mh, danzl df, gausche-hill m et al, editor. philadelphia: pa: mosby/elsevier. 2013. 7. weinberg s. recommended medical books, emcrit 2012 [18 oct. 2017]. available from: https://emcrit.org/recommended-reading. 8. kendirci m. how to write a medical book chapter? turkish journal of urology. 2013;39(suppl 1):37. 9. country rankings, cimago journal & country rank. sjr 2016 [27 oct 2017]. available from: http://www.scimagojr.com/countryrank.php?category= 2711&area=2700&year=2016. 10. yl tsai cl, sc chen and zs yen. top-cited articles in emergency medicine. am j emerg med. 2006;24(6):64757. 11. emergency medicine country rankings, cimago journal & country rank. sjr 1996 [27 oct 2017]. available from: http://www.scimagojr.com/countryrank.php?category= 2711&area=2700&year=1996. 12. emergency medicine journal rankings, cimago journal & country rank. sjr 2016 [27 oct 2017]. available from: http://www.scimagojr.com/journalrank.php?area=2700 &category=2711. 13. liang y, ge h-x, ma q-b. analysis of the impact factor of emergency medicine journals in the past 10 years. chinese medical journal. 2016;129(20):2504. 14. paltved c, musaeus p. qualitative research on emergency medicine physicians: a literature review. international journal of clinical medicine. 2013;3(07):772. 15. choi j, you js, joo ys. a bibliometric analysis of research productivity of emergency medicine researchers in south korea. clinical and experimental emergency medicine. 2016;3(4):245. 16. li q, jiang y, zhang m. national representation in the emergency medicine literature: a bibliometric analysis of highly cited journals. the american journal of emergency medicine. 2012;30(8):1530-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods: results: discussion: limitations conclusion: appendix references archives of academic emergency medicine. 2020; 8(1): 81 or i g i n a l re s e a rc h success rate of endotracheal intubation using inline stabilization with and without cervical hard collar; a comparative study welawat tienpratarn1, chaiyaporn yuksen1, kasamon aramvanitch1, karn suttapanit1, yahya mankong1, nussareen yaemluksanalert1, sansanee meesawad1∗ 1. department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, bangkok 10400, thailand. received: august 2020; accepted: september 2020; published online: 10 october 2020 abstract: introduction: application of a rigid cervical collar may interfere with the laryngeal view, and potentially lead to failed endotracheal intubation (eti). this study aimed to compare intubation success rates while performing inline stabilization with and without cervical hard collar. methods: this randomized prospective comparative study included paramedics working in the department of emergency medicine, ramathibodi hospital, mahidol university, bangkok, thailand to compare the success rates of endotracheal intubation on manikin using inline stabilization with and without cervical hard collar. results: 125 participants were evaluated; 63 in the rigid cervical collar and 62 in the non-cervical hard collar group. the rate of successful intubation was significantly higher using manual stabilization without cervical hard collar (61 (96.8%) vs. 55 (88.7%); p=0.048). the time required to successfully perform intubation was also shorter, with manual stabilization only (14.1 ±20.9 vs. 18.9±29.0; p = 0.081). conclusion: it seems that, removal of the rigid cervical collar during eti in patients with suspected traumatic spine injury could increase the intubation success rate. keywords: intubation, intratracheal; spinal injuries; multiple trauma; restraint, physical cite this article as: tienpratarn w, yuksen ch, aramvanitch k, suttapanit k, mankong y, yaemluksanalert n, meesawad s. success rate of endotracheal intubation using inline stabilization with and without cervical hard collar; a comparative study. arch acad emerg med. 2020; 8(1): e81. 1. introduction traumatic spinal injury (tsi) is one of the most common lifethreatening traumatic conditions. it can injure nearby organs, such as the spinal cord, which can cause severe complications ranging from minor injuries to disability or death (1). there is an average incidence of 10.5 spinal injuries per 100,000 people worldwide or approximately 768,473 incidents per year. the most common cause is traffic accidents followed by falls; about 48.8% of spinal injuries require surgery (2). in patients with suspected tsi, transportation requires a rigid cervical collar, head immobilization device, and spinal support throughout the lifting and moving procedure (3). in pa∗corresponding author: chaiyaporn yuksen; department of emergency medicine, faculty of medicine, ramathibodi hospital, mahidol university, 270 rama vi road, thung phaya thai, ratchathewi, bangkok, thailand, 10400. e-mail: chaipool0634@hotmail.com, tel: (+66)8-3183-1373, fax: (+66)-22012404 tients with a threatened airway, essential preliminary treatments are required for preventing airway obstruction and providing adequate ventilation support (1). in tsi patients, tracheal intubation must be performed carefully to prevent further injury to the cervical spine and spinal cord (4). moreover, manual inline stabilization using a rigid cervical collar is recommended to reduce the movement of the cervical spine during tracheal intubation (5). using a rigid cervical collar and performing manual inline stabilization in patients suspected to have a cervical tsi can reduce the intubation-related movement of the cervical spine and aggravation of tsi (6). but the application of a rigid cervical collar can cause difficulty in airway management, decrease the inter-incisor, increase the mallampati classification, decrease the angles of neck extension, and reduce cervical spine movements (7). removing the rigid cervical collar or anterior portion during tracheal intubation has been suggested by an expert physician. manual inline stabilization is a maneuver in which the care provider is standing at the patient’s head, using the palms of both hands to grip the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. tienpratarn et al. 2 sides of the patients’ head, which is reportedly a safe technique to perform during intubation. using a rigid cervical collar and performing manual inline stabilization in patients suspected to have a cervical tsi can reduce the intubationrelated movement of the cervical spine (8). however, no reports have clearly described intubation success rates while using a rigid cervical collar and whether it is necessary to remove the rigid cervical collar during intubation. this study aimed to compare intubation success while using a rigid cervical collar along with manual inline stabilization versus manual inline stabilization alone when performed by paramedics on a manikin. 2. methods 2.1. study design and setting this randomized prospective comparative study included paramedics working at the department of emergency medicine, ramathibodi hospital, mahidol university, bangkok, thailand to compare the success rate of endotracheal intubation on manikin using inline stabilization with and without cervical hard collar. this study was approved by the institutional ethics committee board of ramathibodi hospital faculty of medicine, mahidol university. the ethics approval reference number is mura2018/900. 2.2. participants eligible paramedic students who provided a signed consent to participate in the research were included and those who refused to participate were excluded. participants were randomly assigned to endotracheal intubation using inline stabilization either with rigid cervical collar or without it using sequentially numbered opaque sealed envelopes and sixblock randomization. participants in the rigid cervical collar group performed intubation with a rigid cervical collar and manual inline stabilization and others performed intubation using manual inline stabilization without a rigid cervical collar (figure 1). 2.3. definitions and procedures the data recorded in this study included the success of intubation within 60 seconds. successful intubation was defined as the endotracheal tube’s insertion into the manikin’s bronchus in a maximum of two attempts. the successful intubation time was defined as the period from passing the equipment through the axial plane of manikin’s front teeth to successful intubation. the viewpoint of intubation was defined as the viewpoint of the larynx during intubation, based on mallampati classification. the manikin was not moved, nor was the rigid collar removed. the rigid cervical collar position was measured each time intubation was conducted to ensure it was in the same position. only one set of equipment, comprising of a macintosh laryngoscope and no. 3 blades, was used in the study. only one no. 7 endotracheal tube was used in the study. the equipment was tested for readiness before each intubation procedure, and the manikin was fixed in the original location and position. the duration of the study was two months, and we used the same manikin and equipment. 2.4. data gathering the researcher recorded demographic variables of participants, intubation success, time to the success of intubation, and the laryngeal view grade for each participant, using a predesigned checklist. 2.5. statistical analysis for sample size estimation, we used the data from a pilot study of 20 paramedics intubating a manikin. the pilot study was done in ramathibodi hospital. the rate of intubation success within 60s in groups with and without collar was 92% and 70%, respectively. with a 95% confidence interval and power of 80%, the sample size ratio 1:1, and p = 0.05, the twosided test found that the minimum sample size should be 58 subjects. chi-square and fisher’s exact tests were used to compare the categorical data. mcnemar’s test and t-test of rank-sum tests were used for the comparison of continuous data. all statistical analyses were performed using stata software version 14 (statacorp, college station, tx, usa). p < 0.05 was considered statistically significant. 3. results 125 participants were evaluated; 63 in the rigid cervical collar and 62 in the non-cervical hard collar group. table 1 compares the baseline characteristics of participants. there were no statistically significant differences between groups regarding age (p =0.925), sex (p = 0.864), weight (p = 0.889), height (p = 0.985), and intubation experience (p = 0.878). the success of intubation was significantly higher with only manual inline stabilization compared to using the rigid cervical collar and manual inline stabilization (61 (96.8%) vs. 55 (88.7%); p = 0.048). the intubation time was shorter with only manual inline stabilization (14.1 ±20.9 vs. 18.9±29.0; p = 0.081). comparison between the intubation characteristics of the 2 groups is presented in table 2. 4. discussion the results showed that the overall rate of successful intubation was significantly higher when using manual inline stabilization alone. additionally, the laryngeal view grade was not significantly different between the two groups. in every trauma patient with suspected tsi, the cervical spine this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): 81 figure 1: endotracheal intubation using inline stabilization with and without rigid cervical collar on manikin. table 1: comparing the baseline characteristics of participants between groups variables intubation groups p values inline (n = 63) inline + collar (n = 62) age (year) mean ± sd 23.5±5.1 23.2±4.2 0.925 gender n (%) male 32 (50.8) 31 (50.0) 0.864 female 31(49.2) 31 (50.0) weight (kg) mean ± sd 63.9 ± 16.1 64.5 ± 9.5 0.889 height (m) mean ± sd 166.7 ± 8.0 166.4 ± 18.7 0.985 intubation experience (year) pre-clinical year paramedics 45 (71.4) 44 (71.0) 0.878 clinical year paramedics 18 (28.6) 18 (29.0) data are presented as mean ± standard deviation (sd) or number (%). table 2: comparing the intubation characteristics between groups variables intubation groups p inline (n = 63) inline + collar (n = 62) successful intubation number (%) 61 (96.8) 55 (88.7) 0.048 time to successful intubation (second) mean ± sd 14.1 ±20.9 18.9±29.0 0.081 attempts of successful intubations n (%) 1 52 (82.5) 50 (80.6) 2 9 (14.3) 5 (8.1) 0.098 ≥3 (failed) 2 (3.2) 7 (11.3) laryngeal view grade* n (%) 1 19 (30.1) 14 (22.6) 2 32 (50.8) 32 (51.6) 0.675 3 11 (17.5) 15 (24.2) 4 1 (1.6) 1 (1.6) time to first successful intubation (second) mean ± sd 17.4 ± 14.4 18.8 ± 11.7 0.592 *based on mallampati classification. should be manually maintained in a neutral position before the primary survey and resuscitation. applying a rigid cervical collar, stabilizing the body to a spinal board, and adequate external immobilization of the head should be performed. en route to the trauma center or emergency department (ed), if the tsi patients need assisted ventilation or enthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem w. tienpratarn et al. 4 dotracheal tube intubation, cervical collar might better be removed. on the scene or en route, eti should be successful in a short period to prevent hypoxia and aspiration. it seems beneficial to remove the rigid cervical collar during eti because it increases the success rate and shortens intubation time. on scene or en route eti is more difficult than ed intubation and a video laryngoscope, which improves laryngeal views, may not be available in prehospital care. emergency medical service providers could remove the cervical collar and only apply manual inline stabilization before eti for improving laryngeal views. one study that evaluated intubation of patients using the rigid cervical collar and manual inline stabilization showed that both methods could stabilize the cervical spine. however, using rigid cervical collar, intubation success rate was reduced, and the laryngeal view was impaired. in addition, the applied methods were shown to significantly increase the time of intubation (9). another study found that using a rigid cervical collar could reduce the movement of the spine, but performing eti was significantly more difficult (7). the study by kleine-brueggeney m. et al. shows that the rigid cervical collar can cause limitations in mouth opening and significantly increase intubation time (10). the study by yuk m. et al. was performed on 76 healthy volunteers in a simulation study and showed that the lemon criteria (mouth opening, modified mallampati classification, and neck extension) worsened significantly after rigid cervical collar application (7). the study by yuksen c et al., comparing the efficiency of intubation between a video laryngoscope and macintosh laryngoscope on a manikin with a hard collar that restricted neck movement, showed that intubation success was significantly lower when using the macintosh laryngoscope compared to when a video laryngoscope was used in the group of personnel who had experience performing intubation. in the inexperienced group, however, the time to successful intubation was not different between the two methods (11). this study was done including senior paramedic students whose endotracheal intubation skill was similar to paramedic physicians. the results of this study may be used in the practice of eti to remove the rigid cervical collar, especially in a prehospital setting with time limitation. 5. limitations there are some limitations to this study. first, the results of this study may not apply to real clinical situations as they were found using a manikin; but they may be used as preliminary data for further research. second, using a manikin might have caused bias in evaluating the mallampati score, which should be further investigated by assessing the participant’s laryngeal view report. deterioration of the equipment such as an endotracheal tube, guidewire, and energy of battery of macintosh laryngoscope might have caused bias and confounded our study results. 6. conclusion it seems that, removal of the rigid cervical collar during eti in patients with suspected tsi could increase the intubation success rate. 7. declarations 7.1. acknowledgements we thank angela morben, dvm, els, from edanz group (www.edanzediting.com/ac), for editing a draft of this manuscript. 7.2. conflict of interest statement none of the authors have any conflicts of interest to disclose. 7.3. source of funding the publication funding support by ramathibodi hospital, mahidol university. 7.4. data availability statement the data are not available for public access because of participants privacy concern but are available from the corresponding author upon reasonable request. 7.5. authors’ contribution all authors met the criteria for gaining authorship based on the recommendations of the international committee of medical journal editors. references 1. xiong c, hanafy s, chan v, hu zj, sutton m, escobar m, et al. comorbidity in adults with traumatic brain injury and all-cause mortality: a systematic review. bmj open. 2019;9(11). 2. kumar r, lim j, mekary ra, rattani a, dewan mc, sharif sy, et al. traumatic spinal injury: global epidemiology and worldwide volume. world neurosurgery. 2018;113:e345-e63. 3. kreinest m, gliwitzky b, schuler s, grutzner pa, mãijnzberg m. development of a new emergency medicine spinal immobilization protocol for trauma patients and a test of applicability by german emergency care providers. scandinavian journal of trauma, resuscitation and emergency medicine. 2016;24(1):1-10. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): 81 4. liao s, popp e, huttlin p, weilbacher f, munzberg m, schneider n, et al. cadaveric study of movement in the unstable upper cervical spine during emergency management: tracheal intubation and cervical spine immobilisation–a study protocol for a prospective randomised crossover trial. bmj open. 2017;7(8):e015307. 5. chan w-h, cheng c-p, chiu y-l, hsu y-c, hu m-h, huang g-s. two head positions for orotracheal intubation with the trachway videolight intubating stylet with manual in-line stabilization: a randomized controlled trial. medicine. 2020;99(17):e19645. 6. liao s, schneider nr, hãijttlin p, grãijtzner pa, weilbacher f, matschke s, et al. motion and dural sac compression in the upper cervical spine during the application of a cervical collar in case of unstable craniocervical junction–a study in two new cadaveric trauma models. plos one. 2018;13(4):e0195215. 7. yuk m, yeo w, lee k, ko j, park t. cervical collar makes difficult airway: a simulation study using the lemon criteria. clinical and experimental emergency medicine. 2018;5(1):22. 8. oh h, kim h, yoon h-k, lee h-c, park h-p. no radiographic index predicts difficult intubation using the optiscopeâďć in cervical spine surgery patients: a retrospective study. bmc anesthesiology. 2020;20(1):1-10. 9. kim jw, lee kr, hong dy, baek kj, lee yh, park so. efficacy of various types of laryngoscope (direct, pentax airway scope and glidescope) for endotracheal intubation in various cervical immobilisation scenarios: a randomised cross-over simulation study. bmj open. 2016;6(10):e011089. 10. kleine-bruggeney m, greif r, schoettker p, savoldelli gl, nabecker s, theiler l. evaluation of six videolaryngoscopes in 720 patients with a simulated difficult airway: a multicentre randomized controlled trial. bja: british journal of anaesthesia. 2016;116(5):670-9. 11. yuksen c, prachanukool t, chinsupaluk w, trainarongsakul t. videolaryngoscope versus macintosh laryngoscope in stimulated patients with limitation of neck movements. ramathibodi medical journal. 2014;37(2):71-80. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references archives of academic emergency medicine. 2020; 8(1): e82 or i g i n a l re s e a rc h henna-induced hemolysis and acute kidney injury in an 85-year-old man; a case report sahel asgari1, mohsen esfandbod2, maryam haghshomar3∗ 1. faculty of medicine, tehran university of medical sciences, tehran, iran. 2. hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran. 3. faculty of medicine, students’ scientific research center, tehran university of medical sciences, tehran, iran. received: august 2020; accepted: september 2020; published online: 14 october 2020 abstract: henna is a commonly used traditional cosmetic agent, which also holds medical potentials and is used to treat skin lesions including seborrheic dermatitis or fungal infections and also has possible anti-inflammatory effects. it contains lawsone (2-hydroxy-1,4-naphthoquinone) and, therefore, has the potential to induce oxidative hemolysis. henna-induced hemolysis has been previously reported in children with glucose 6-phosphate dehydrogenase deficiency. here, we report an 85-year-old man who developed hemolytic anemia and acute kidney injury following oral consumption of henna to help his dyspnea. he was treated with hydration, bicarbonate, and dexamethasone. over the course of hospitalization, the patient developed ventilator-associated pneumonia and was treated with antibiotic. he was discharged after one month. this finding is of high importance due to common use of henna, especially among people with false beliefs regarding traditional and herbal medicine, and highlights the role of a full history taking. keywords: case reports; hemolysis; lawsonia plant; toxicity; herbal medicine; anemia, hemolytic; acute kidney injury cite this article as: asgari s, esfandbod m, haghshomar m. henna-induced hemolysis and acute kidney injury in an 85-year-old man; a case report. arch acad emerg med. 2020; 8(1): e82. 1. introduction hemolytic anemia is a situation in which disruption of red blood cells (rbcs) happens with a faster speed than their reproduction and is accompanied with a decrease in hemoglobin. its etiology is divided into inherited and acquired. certain medications, chemicals, toxins, and herbal medicines can cause hemolytic anemia (1). drug-induced immune hemolytic anemia (diiha) is an uncommon phenomenon caused by an immune response to a drug following its administration (2). this reaction is caused either by antibody-mediated complement activation, which results in an intravascular hemolysis, or antibody-mediated phagocytosis, which results in an extravascular hemolysis. since the first discovery of diiha, a large number of drugs have been reported to cause positive direct anti-globulin test (dat) (3). penicillin and its derivates, cephalosporins, îš-lactamase inhibitors, and quinidine are the most com∗corresponding author: maryam haghshomar; students’ scientific research center, mirzaye shirazi avenue, tehran, iran. postal code: 1586615113, tel: +989226039842, email: maryam_haghshomar@yahoo.com. mon causes of this uncommon complication (4). chemicals like phenylhydrazine-hcl can induce hemolytic anemia (5). this phenomenon is most likely a side effect of oxidative stress. henna has been reported to lead to this problem in previous case reports (6, 7). here, we report an 85-yearold man who developed hemolytic anemia and acute kidney injury following oral consumption of henna to help his dyspnea. recognizing this rare complication caused by a common traditional cosmetic agent is of high importance due to common use of henna, especially among people with false beliefs regarding traditional and herbal medicine, and highlights the role of a full history taking. 2. case presentation 85-year-old men presented to emergency department (ed) with chief complain of abdominal pain and constipation from 3 days prior to admission. he hadn’t passed any gas during those days. pain was not related to eating. on admission, his general examination and vital signs showed restlessness, icteric sclera, generalized wheezing in lung auscultation, peri-umbilical tenderness, mild tachycardia (heart rate 100 bpm), tachypnea (respiratory rate 32), decreased o2 satthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. asgari et al. 2 uration (78% in room air) and wide pulse pressure (150/70 mmhg). the patient was admitted to general surgery service in ed. abdominal ultrasonography and computed tomography (ct) scan were normal and chest x-ray showed some levels of increased air. medical history of the patient revealed nothing significant, except for some unclear respiratory system problems, dyspnea suggestive of possible smoking history, and chronic obstructive pulmonary disease (copd). due to presence of jaundice, an initial lab examination was performed with the aim of evaluating liver and gallbladder function, which found reduced hemoglobin (hb) (9.5 g/dl) and rbc count (3000000 number/ml) (table 1). moreover, lab results showed increase in lactate dehydrogenase (ldh)(3273 u/l), c-reactive protein (crp) (139.6 mg/l), ferritin (>2000 µg/l), aspartate aminotransferase (ast u/l) (78), prothrombin time (pt) (14.7 seconds), international normalized ratio (inr) (1.17 seconds), potassium (k) (5.93 mmol/l), urea (94 mg/dl), white blood cell (wbc) (36000 number/ml), bilirubin total (9.93 mg/dl), and bilirubin direct (1.02 mg/dl) (table 1). urine analysis (ua), manifested a 4+ proteinuria and 1+ glycosuria (table 2). morphine was present in urine toxicology (table 2). on the third day of admission, lab tests were ordered following consultation with an internal medicine specialist due to patient’s fever and loss of consciousness. on that day, the patient arrested but fortunately successful cardiopulmonary resuscitation (cpr) was performed. emergency service intubated the patient and started full cardiac monitoring. lab results showed hemolysis with a severe loss of rbc count (1030000 number/ml) and hb level (3.5 g/dl) along with sustained increased ferritin (>2000 µg/l), urea(130), bilirubin total (6.68 mg/dl), and bilirubin direct (1.8 mg/dl). furthermore, direct and indirect coombs test appeared negative and glucose 6 phosphate dehydrogenase (g6pd) levels were in normal range (12.0 units/g). moreover, the patient had developed acute kidney injury (aki) marked by an elevated creatinine (2.23 mg/dl). peripheral blood smear showed schistocytes and other fragmented rbcs. elevated serum bilirubin, alanine aminotransferase (alt), lactate dehydrogenase (ldh), and peripheral blood smear results led us to hemolytic anemia diagnosis. following the diagnosis of hemolytic anemia, the patient’s diet was reinvestigated through his family members and his wife, which revealed oral consumption of henna. henna was prescribed by a traditional medicine physician to help the patient’s dyspnea. henna powder was dissolved in a glass of water and the patient had drank a glass a day, for 2 consecutive days prior to admission. hematology consultant made a diiha diagnosis based on the history of henna consumption, clinical findings, and laboratory results of hemolysis. following this diagnosis, 4 mg dexamethasone three times a day (tds) was prescribed for the patient. hydration and bicarbonate therapy were performed to treat the aki. the patient’s condition was improved; however, after a few days he developed fever and a ventilator-associated pneumonia (vap) was diagnosed, and an infectious disease specialist started antibiotic therapy. the patient was discharged after one month. two weeks later, the patient referred to the hospital with cbc, cr level, and g6pd level results. g6pd level was rechecked as the enzyme levels might not be low in the acute hemolysis phase. all test appeared within normal range. 3. discussion henna is a traditional cosmetic agent applied over skin, hair, or nails as a dye. it is derived from lawsonia alba shrub and it contains lawsone (2hydroxy–1,4 napthoquinon). black henna contains paraphenylenediamine (ppd). in some countries in africa, south east asia, and middle east, henna is commonly used in ceremonies to create patterns on the skin. in addition to cosmetic uses, it has anti-inflammatory affects, which makes it suitable for seborrheic dermatitis or fungal infections therapy. studies have suggested antiinflammatory, antipyretic, and analgesic effects for henna (8). lawsone has a structure and redox potential similar to orthosubstituted 1, 4-naphthoquinones, which is an oxidant of g6pd and normal rbcs, and henna absorption may lead to oxidative injury (9). ppd is also an oxidative chemical allergen that can cause adverse systemic effects such as laryngeal edema and respiratory distress, often demanding emergency tracheostomy and leading to aki, rhabdomyolysis, and multiple organ failure (10). the patient had obstruction symptoms like abdominal pain and constipation, and also suffered from aki and acute respiratory distress, which led to his intubation, and taken together, they seem highly compatible with henna toxicity. although henna absorption has a high risk of hemolytic anemia, merely a few reports of diiha due to henna application are present. cases report acute renal failure associated with henna use along with hemolytic anemia. previously, most cases of henna-induced hemolysis had been reported in newborns and infants. deveciglu et al. reported hemolytic anemia and acute renal failure after cutaneous application of henna to abdomen, intertriginous region, and legs for treating diaper rash, developed in a 27-day-old boy (6). seyedzadeh et al. found severe acute hemolysis in a 42-day old infant followed by topical application of henna for treating his napkin dermatitis (11). ilkhanipur et al. described a 35-day old, g6pd-deficient boy who had advanced jaundice, hemogluinuria, and kernicterus symptoms after cutaneous intake of henna (12). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e82 table 1: laboratory findings of the patient measures day 1 day 3 normal range ph 7.40 7.35-7.45 pco2 (torr) 38.7 35-45 lactate dehydrogenase (u/l) 3273 5010 <480 c-reactive protein (mg/l) 139.6 <3.0 ferritin (µg/l) >2000 >2000 35-300 folic acid (ng/ml) 13.3 2-20 vitamin b12 (ng/ml) 548 138-652 blood sugar (mmol/l) 200 180 <200 urea (mg/dl) 94 130 18-55 creatinine (mg/dl) 1.13 2.23 0.6-1.2 natrium (mmol/l) 135 149.8 135-145 potassium (mmol/l) 5.93 5.12 3.5-5 calcium (mmol/l) 8.3 8.2-10.3 magnesium (mmol/l) 2.7 1.8-2.6 aspartate aminotransferase (u/l) 78 10-40 alanine aminotransferase (u/l) 52 7-56 alkaline phosphatase (u/l) 293 44-147 bilirubin total (mg/dl) 9.93 6.68 0.1-1.2 bilirubin direct (mg/dl) 1.02 1.8 <0.4 prothrombin time (seconds) 14.7 11-13.5 partial thromboplastin time (seconds) 31 30-40 international normalized ratio (seconds) 1.17 <1.1 amylase (u/l) 45 30-110 white blood cell (number/mm3 ) 36000 39900 4500-11000 red blood cell, million (number/mm3 ) 3.0 1.03 4.32-5.72 hemoglobin (g/dl) 9.5 3.5 13.5-17.5 hematocrit (%) 11 41-52 mean corpuscular volume (femtoliters) 95.72 106.8 80-96 mch∗ (picograms/cell) 31.25 33.98 27-33 mchc∗∗ (g/dl) 32.65 31.28 33-36 platelets (mm3 ) 285000 207000 150000-450000 red cell distribution (width %) 18.8 23 11.5-14.5 mean platelet volume (femtoliters) 11.3 8-12 platelet distribution (width %) 15.5 10.0-17.9 neutrophil (%) 70.7 40-60 lymphocyte (%) 27.7 20-40 mixed (%) 1.6 4-8 ∗: mean corpuscular hemoglobin; ∗∗: mean corpuscular hemoglobin concentration. table 2: urine analysis and urine toxicology findings of the patient urine toxicology result urine analysis result nitrite negative ph 6.5 morphine positive specific gravity 1.01 amphetamine negative color yellow benzodiazepines negative white blood cell 4-5 buprenorphine negative red blood cell 0-1 cocaine negative glucose 1+ methadone negative protein 4+ tricyclic antidepressant negative cases with older age, are also present. through investigating venous blood exposure with different levels of lawsone in 15 healthy and 4 g6pd-deficient adults, zinkham et al. found that henna is capable of causing oxidative hemolysis, which is more severe and more probable in g6pd-deficient patients (8). kheir et al. reported a case of life-threatening henna-induced hemolytic anemia after application of henna to skin in sudan. this case was a 6-year-old boy who was this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. asgari et al. 4 diagnosed with g6pd deficiency after workup for hemolysis (13). raupp et al. found 4 cases of hemolytic crisis following topical application of henna, all diagnosed with g6pd deficiency. one male and one female neonate, and two boys aged three and 4 years made up the cases (7). qurashi et al. reported a young saudi male who developed aki and intravascular hemolysis following ingestion of henna mixed with para-phenylenediamine (14). moreover, a case of severe hemolytic anemia was reported after voluntary ingestion of henna to induce abortion. the 17-year-old girl year was later diagnosed with g6pd deficiency (15). we are the first to report henna-induced hemolytic anemia in a non-g6pd-deficient patient after oral consumption of henna at an old age. it can be assumed that oral intake of henna will be more potent in causing hemolysis compared to cutaneous absorption. 4. conclusion in conclusion, henna-induced hemolytic anemia is rare and most cases occur in g6pd-deficient individuals during their first months of life or at a young age; however, the chance of hemolysis occurrence in healthy or old individuals cannot be ruled out. since henna is a commonly used herbal agent, clinical suspicion toward henna-induced hemolysis after unexplained hyperbilirubinemia in patients with a history of henna intake is of high importance. more observations and further investigation into the mechanism of this hemolytic reaction seems necessary. it should be highlighted that obtaining a full history of herbal medicines remains critical due to patients’ false beliefs. 5. list of abbreviations drug-induced immune hemolytic anemia (diiha); red blood cells (rbc); direct antiglobulin test (dat); emergency room (er); hemoglobin (hb); lactate dehydrogenase (ldh); creactive protein (crp), ferritin; aspartate aminotransferase (ast); prothrombin time (pt); international normalized ratio (inr); potassium (k); white blood cell (wbc); bilirubin total (bili. t); bilirubin direct (bili. d.); urine analysis (ua); cardiopulmonary resuscitation (cpr); glucose 6 phosphate dehydrogenase (g6pd); acute kidney injury (aki); three times a day (tds); ventilator-associated pneumonia (vap); paraphenylenediamine (ppd) 6. declarations 6.1. ethics consideration this study was approved by department of medical ethics, tehran university of medical sciences with ethic number ir.tums.sinahospital.rec.1399.045. 6.2. availability of data and materials the datasets used during the current study are available from the corresponding author on reasonable request. 6.3. conflict of interests the authors declare that they have no competing interests 6.4. funding this research was supported by the tehran university of medical sciences. 6.5. authors’ contributions sa performed the initial examination of the patient and contributed in the final diagnosis and was a contributor in writing the manuscript. me analyzed and interpreted the patient data regarding the hematological disease. mh was a major contributor in writing the manuscript. all authors read and approved the final manuscript. 6.6. acknowledgements not applicable. references 1. dhaliwal g, cornett pa, tierney jr lm. hemolytic anemia. american family physician. 2004;69(11):2599-606. 2. garratty g. drug-induced immune hemolytic anemia. hematology. 2009;2009(1):73-9. 3. snapper i, marks d, schwartz l, hollander l. hemolytic anemia secondary to mesantoin. annals of internal medicine. 1953;39(3):619-23. 4. sarkar r, philip j, mallhi r, jain n. drug-induced immune hemolytic anemia (direct antiglobulin test positive). medical journal, armed forces india. 2013;69(2):190. 5. lee hw, kim h, ryuk ja, kil k-j, ko bs. hemopoietic effect of extracts from constituent herbal medicines of samul-tang on phenylhydrazine-induced hemolytic anemia in rats. international journal of clinical and experimental pathology. 2014;7(9):6179. 6. devecioglu c, katar s, dogru o, tas m. henna-induced hemolytic anemia and acute renal failure. the turkish journal of pediatrics. 2001;43(1):65-6. 7. raupp p, hassan ja, varughese m, kristiansson b. henna causes life threatening haemolysis in glucose-6phosphate dehydrogenase deficiency. archives of disease in childhood. 2001;85(5):411-2. 8. zinkham wh, oski fa. henna: a potential cause of oxidative hemolysis and neonatal hyperbilirubinemia. pediatrics. 1996;97(5):707-9. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e82 9. mcmillan dc, sarvate sd, oatis jr je, jollow dj. role of oxidant stress in lawsone-induced hemolytic anemia. toxicological sciences. 2004;82(2):647-55. 10. gude d, bansal dp, ambegaonkar r, prajapati j. paraphenylenediamine: blackening more than just hair. journal of research in medical sciences: the official journal of isfahan university of medical sciences. 2012;17(6):584. 11. seyedzadeh a, hemmati m, gheiny s. henna-induced severe hemolysis: in glucose 6-phosphate dehydrogenase deficiency. pakistan journal of medical sciences. 2007;23(1):119. 12. ilkhanipur h, hakimian n. henna: a cause of life threatening hemolysis in g6pd-deficient patient. pak j med sci. 2013;29(1 suppl):429-31. 13. kheir a, gaber i, gafer s, ahmed w. life-threatening haemolysis induced by henna in a sudanese child with glucose-6-phosphate dehydrogenase deficiency. emhj. 2017;23(1). 14. qurashi he, qumqumji aa, zacharia y. acute renal failure and intravascular hemolysis following henna ingestion. saudi journal of kidney diseases and transplantation. 2013;24(3):553. 15. perinet i, lioson e, tichadou l, glaizal m, de haro l. hemolytic anemia after voluntary ingestion of henna (lawsonia inermis) decoction by a young girl with g6pd deficiency. medecine tropicale: revue du corps de sante colonial. 2011;71(3):292-4. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentation discussion conclusion list of abbreviations declarations references emergency. 2018; 6 (1): e46 br i e f re p o rt quality of cardiopulmonary resuscitation in emergency department based on the aha 2015 guidelines; a brief report ali vafaei1,2, amin shams akhtari1, kamran heidari1,2, somayeh hosseini1∗ 1. department of emergency medicine, loghman hakim hospital, shahid beheshti university of medical sciences , tehran, iran. 2. hearing disorders research center, loghman hakim hospital, shahid beheshti university of medical sciences, tehran, iran. received: june 2018; accepted: july 2018; published online: 21 july 2018 abstract: introduction: adhering to existing guidelines on cardiopulmonary resuscitation (cpr) can increase the survival rate of the patients. the present study has been designed with the aim of determining the quality of cpr performed in the emergency department based on the latest protocol by the american heart association (aha). methods: in this prospective cross-sectional study cpr process was audited in patients above 18 years old in need of cpr presenting to the emergency departments of 3 teaching hospitals based on the aha 2015 guidelines. less than 60% agreement was considered as fail, 60-70% as poor, 70-80% as moderate, 80-90% as good, and 90-100% as excellent. results: 80 cases of cpr were audited (55% male). location of arrest was the hospital in 58 (72.5%) cases and 48 (60.0%) of the cases happened during the day. 28 (35.0%) cases had orotracheal intubation before the initiation of cpr. 30 (37.5%) patients had a shockable rhythm at the initiation of cpr. based on the findings, out of the 31 studied items, 9 (29.03%) had excellent agreement, 10 (32.25%) had good, 4 (12.90%) had moderate, 2 (6.45%) had poor, and 6 (19.35%) had fail agreement rate. conclusion: based on the findings of the present study, the quality of applying the principles of basic and advanced cpr in the emergency department of the studied hospital had intermediate, poor and fail agreement with the recommendations of the aha 2015 in at least one third of the cases. keywords: physical education and training; cardiopulmonary resuscitation; clinical audit; emergency service, hospital; internship and residency © copyright (2018) shahid beheshti university of medical sciences cite this article as: vafaei a, shams akhtari a, heidari k, hosseini s. quality of cardiopulmonary resuscitation in emergency department based on the aha 2015 guidelines; a brief report. 2018; 6(1): e46. 1. introduction t hrough the centuries, human has used various and interesting methods for resuscitation of people close to death. paracelsus was the first person that used blacksmith bellows for blowing in the lungs of people who had faced sudden death. this method was commonly used for about 300 years in europe. in the middle of 20th century the term cardiopulmonary resuscitation (cpr) was used for describing the technique of simultaneous cardiac massage and mouth to mouth respiration in a person without a pulse (1, ∗corresponding author: somayeh hosseini ; emergency medicine department, loghman hakim hospital, kamali street, karegar avenue, tehran, iran. tel: +989126054128 email: hosseini.somayeh1392@gmail.com. 2). this technique has significantly improved in a few years, especially regarding use of resuscitation operation in the hospital. in 2000, the international liaison committee on resuscitation held the first international conference of resuscitation for developing international guidelines for cpr and emergency cardiac care so that all individuals working in medical teams and rescuers follow the same protocols when performing resuscitation (3). based on these conditions, high quality cpr is associated with: ensuring sufficient chest massage, proper depth, allowing chest recoil, minimizing the delay in massage, and avoiding too much ventilation. currently, despite many attempts at cpr being unsuccessful, it is still an internationally accepted treatment operation (4, 5). adhering to latest existing guidelines and performing these guides with high quality in cpr can increase the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 2 survival rate of the patients. proofs of this claim are studies that show with correct training and giving proper feedback to the resuscitation team, percentage of successful cpr and its proper performance increase significantly (6-9). yet, some researchers express that there isn’t a proper agreement between what happens at the clinic with international cpr guidelines (10, 11). these inadequacies lead to improper perfusion in the cardiac and brain tissues and result in the poor outcome of the patient. normally, evaluating the existing state is the first step taken in planning for other steps to improve the quality. therefore, the present study has been designed with the aim of determining the quality of cpr performed in the emergency department based on the latest protocol by the american heart association (aha). 2. methods 2.1. study design and setting in this prospective cross-sectional study on resuscitation, patients above 18 years old in need of cpr presenting to the emergency departments of loghmane hakim, imam hossein, and shohadaye tajrish teaching hospitals, tehran, iran, from march 2017 to march 2018 were evaluated. protocol of this study was approved by the ethics committee of shahid beheshti university of medical sciences. in the evaluated emergency department all cprs were performed by a team of emergency medicine and internal medicine residents. 2.2. data gathering the standard technique was defined based on the latest standard guidelines of aha 2015 for cpr. the evaluated items included: status of cpr initiation, status of applying pressure on the chest, the proper place for applying pressure, the number and depth of pressure applied, the number of ventilations per minute, ceasing pressure application for 10 seconds, evaluating the patient’s pulse, using electric shock, rapid initiation of cpr after shock, using vasopressor, switching personnel for applying pressure, using anti-arrhythmic medications, time interval between vasopressor doses, timing of using vasopressor drugs, timing of reaching safe airways, duration of cpr performance, correct prescription of alternative drugs, considering the 5h/5t, airway management, continuous evaluation of patient’s situation, expressing measures such as checking level of consciousness, respiration and pulse, status of the team members (proper, improper), status of oxygen therapy and monitoring of the patient and establishing venous flow. a trained senior emergency medicine resident was responsible for data gathering (approved by 3 emergency medicine professors) in various shifts (day, night), using consecutive sampling by being present at the bedside of patients who needed cpr. 2.3. statistical analysis considering 29% proper cpr performance (8), 95% confidence interval, 90% power, and the minimum considerable clinical significance of 10% the sample size was estimated to be 79 cases. in this study, based on likert scale, less than 60% agreement rate with the aha 2015 guidelines was considered as fail, 60-70% as poor, 70-80% as moderate, 80-90% as good, and 90-100% as excellent. 3. results: 80 cases of cpr were evaluated in the mentioned emergency department (55% male). location of arrest was the hospital in 58 (72.5%) cases and 48 (60.0%) of the cases happened during the day. 28 (35.0%) cases had orotracheal intubation before the initiation of cpr. 30 (37.5%) patients had a shockable rhythm at the initiation of cpr. the rate of adherence to the principles of cpr by the resuscitation team has been summarized in table 1. based on the findings, out of the 31 studied items, 12 (38.70%) had moderate or worse agreement with the principles recommended by the aha 2015 guidelines. 4. discussion based on the findings of the present study, the quality of applying the principles of basic and advanced cpr in the emergency department of the studied hospital had intermediate, poor and fail agreement with the recommendations of the aha 2015 in at least one third of the cases. the final success rate of in-hospital cpr that leads to discharge of the patient from hospital has been estimated to be 9% to 12% (10-12). ko et al. assessed the quality of cpr in pre-hospital settings and showed that performance of cpr had an acceptable quality in only 29% of the cases (8). hossein-nejad et al. also performed a study in rasoole akram hospital and showed that in only 25 (75.75%) of their studied cpr cases chest massage, pulmonary ventilation, pulse check, insertion of peripheral vein and intubation were performed correctly (13). taha et al. in 2014 expressed that performance of quality cpr had a considerable effect on the survival of the patients and evaluated various factors affecting the initiation of spontaneous blood circulation and survival of the patients after cardiopulmonary arrest in hospital. these researchers showed that applying pressure in the chest is done in 99.2% of the patients, applying pressure with at least 2 inches of depth in 92.4% of the patients, and stopping it for less than 10 seconds is done in only 48.7% of the patients (14). sutton et al. also showed that cpr of children in hospital is not in agreement with the aha guidelines in most cases (7). a study by christopher crowe et al. in 2015 in the united this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e46 table 1: the rate of adherence of the resuscitation team to the principles of cardiopulmonary resuscitation (cpr) based on the recommendations of american heart association (aha) 2015 activity number (%) asking for help, ringing the bell, rapidly informing the cpr team 78 (97.5) all members of cpr team being present 74 (92.5) having a predefined place and role for cpr team members 46 (57.5) starting cpr without delay 58 (72.5) proper management of the team by the leader 64 (80.0) loudly expressing the measures taken by the team 14 (17.5) applying the basic principles of airway management 28 (53.8) applying advanced principles of airway management 47 (81.1) doing intubation at the proper time 47 (81.1) delay in intubation 23 (28.7) proper number of ventilations in the intubated patient 44 (55.0) applying the 30 to 2 ratio in cardiac massage 10 (20.8) performing proper number of cardiac massages per minute 40 (50.0) applying the standard depth for cardiac massage 48 (60.0) doing the cardiac massage correctly 64 (80.0) allowing chest recoil after applying pressure 48 (60.0) applying the 80% ratio of massage duration to the total time of cpr 80 (100.0) not putting cardiac massage before venipuncture 8 (8.7) massagers changing every 2 minutes 61 (76.3) checking the pulse for 10s between massages every 2 minutes 65 (81.5) connecting the patient to monitor or defibrillator 80 (100.0) using electroshock if needed 24 (80.0) precautions for connection for the team before performing a shock 16 (66.7) applying the proper cycle of shock-massage 16 (66.7) proper medication with the proper dose after giving each shock 22 (91.7) performing massaging for 2 minutes after each shock 48 (96.0) prescribing epinephrine each 3 to 5 minutes 50 (100.0) assessing and treating the cause of arrest during cpr 36 (45.0) covering the patients during cpr 70 (87.5) applying the standards of giving bad news to the relatives 71 (87.7) the in-charge physician informing the relatives 63 (87.7) table 2: the overall status of applying the principles of resuscitation in the studies cases based on the standards of american heart association (aha) 2015 status number (%) excellent 9 (29.03) good 10 (32.25) moderate 4 (12.90) poor 2 (6.45) fail 6 (19.35) states with the aim of evaluating the quality of cpr in emergency deaprtment and the effect of receiving simultaneous audio visual feedback and receiving a report after the incident. the results of the study showed a significant improvement in some cpr indices such as depth of chest massage and the speed of massage, and no considerable change in some indices such as chest massage not being continuous (9). in addition, the results of a systematic review introduced planning, leading and communication as the 3 main entangled mechanisms of coordination during cpr performance (15). it seems that by using tools such as continuous and up to date training as well as getting reports and giving audio visual feedback during cpr we can take steps towards improving the quality of cpr and increase its agreement with the existing standards. this can lead to an increase in the number of successful cpr cases and survival of more patients. 5. conclusion based on the findings of the present study, the quality of applying the principles of basic and advanced cpr in the emergency department of the studied hospital had intermediate, poor and fail agreement with the recommendations of the aha guidelines 2015 in at least one third of the cases. 6. appendix 6.1. acknowledgements the authors would like to thank the clinical research development unit(crdu) of loghman hakim hospital, shahid this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com a. vafaei et al. 4 beheshti university of medical sciences, tehran, iran for their support, cooperation and assistance throughout the period of study (grant number : 12944). 6.2. author contribution all the authors of this article met the standard criteria of authorship based on the recommendations of international committee of medical journal editors. 6.3. funding and support all the expenses of this study were paid by the researchers. 6.4. conflict of interest hereby, the authors declare that there is no conflict of interest regarding the present study. references 1. safar p, escarraga la, chang f. upper airway obstruction in the unconscious patient. journal of applied physiology. 1959;14(5):760-4. 2. cooper ja, cooper jd, cooper jm. cardiopulmonary resuscitation. history, current practice, and future direction. 2006;114(25):2839-49. 3. guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. part 6: advanced cardiovascular life support: section 1: introduction to acls 2000: overview of recommended changes in acls from the guidelines 2000 conference. the american heart association in collaboration with the international liaison committee on resuscitation. circulation. 2000;102(8 suppl):i86-9. 4. johnson bv, coult j, fahrenbruch c, blackwood j, sherman l, kudenchuk p, et al. cardiopulmonary resuscitation duty cycle in out-of-hospital cardiac arrest. resuscitation. 2015;87:86-90. 5. rubertsson s, lindgren e, smekal d, ostlund o, silfverstolpe j, lichtveld ra, et al. mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the linc randomized trial. jama. 2014;311(1):53-61. 6. abella bs, alvarado jp, myklebust h, edelson dp, barry a, o’hearn n, et al. quality of cardiopulmonary resuscitation during in-hospital cardiac arrest. jama. 2005;293(3):305-10. 7. sutton rm, niles d, french b, maltese mr, leffelman j, eilevstjonn j, et al. first quantitative analysis of cardiopulmonary resuscitation quality during inhospital cardiac arrests of young children. resuscitation. 2014;85(1):70-4. 8. ko pc-i, chen w-j, lin c-h, ma mh-m, lin f-y. evaluating the quality of prehospital cardiopulmonary resuscitation by reviewing automated external defibrillator records and survival for out-of-hospital witnessed arrests. resuscitation. 2005;64(2):163-9. 9. crowe c, bobrow bj, vadeboncoeur tf, dameff c, stolz u, silver a, et al. measuring and improving cardiopulmonary resuscitation quality inside the emergency department. resuscitation. 2015;93:8-13. 10. hinkelbein j, spelten o, marks j, hellmich m, bãűttiger bw, wetsch wa. an assessment of resuscitation quality in the television drama emergency room: guideline non-compliance and low-quality cardiopulmonary resuscitation lead to a favorable outcome? resuscitation. 2014;85(8):1106-10. 11. nishiyama c, kitamura t, shimamoto t, kawamura t, sakamoto t, iwami t. quality of cardiopulmonary resuscitation by bystanders and survival after out-of-hospital cardiac arrest. am heart assoc; 2014. 12. nolan jp. high-quality cardiopulmonary resuscitation. current opinion in critical care. 2014;20(3):227-33. 13. hossein-nejad h, afzalimoghaddam m, hoseinidavarani h, nedai hh-n. the validity of cardiopulmonary resuscitation skills in the emergency department using videoassisted surveillance: an iranian experience. acta medica iranica. 2013;51(6):394. 14. taha hs, bakhoum sw, kasem hh, fahim ma. quality of cardiopulmonary resuscitation of in-hospital cardiac arrest and its relation to clinical outcome: an egyptian university hospital experience. the egyptian heart journal. 2015;67(2):137-43. 15. castelao ef, russo sg, riethmuller m, boos m. effects of team coordination during cardiopulmonary resuscitation: a systematic review of the literature. journal of critical care. 2013;28(4):504-21. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results: discussion conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e85 or i g i n a l re s e a rc h effectivness of nebulized budesonide for copd exacerbation management in emergency department; a randomized clinical trial mehrad aghili1,2, elnaz vahidi1,2∗, narges mohammadrezaei1,2, tina mirrajei1, atefeh abedini3 1. department of emergency medicine, shariati hospital, tehran university of medical sciences, tehran, iran. 2. prehospital and hospital emergency research center, tehran university of medical sciences, tehran, iran. 3. chronic respiratory diseases research center, national research institute of tuberculosis and lung, masih daneshvari hospital, shahid beheshti university of medical sciences. received: september 2020; accepted: september 2020; published online: 28 october 2020 abstract: introduction: nebulized budesonide has been long used in chronic obstructive pulmonary disease (copd) exacerbation. this study aimed to compare the effectiveness of nebulized budesonide (nb) versus oral prednisolone (op) in increasing peak expiratory flow rate (pefr) of copd patients in emergency department (ed). methods:patients with copd exacerbation, referring to ed were enrolled in this randomized trial study. in the first group, nb 0.5 mg every 30 minutes till three doses, placebo tablet, and standard treatment was administered. in the second group, nebulized normal saline, op tablet 50 mg, and standard treatment were administered. patients’ demographic data, vital signs, pefr, venous blood gas (vbg) analysis, disposition, and patient and physician satisfaction were all collected and compared between the two groups. results: 43 patients in the nb group and 41 patients in the op group were evaluated. the two groups had similar age (p=0.544) and gender (p=0.984) distribution, duration of illness (p=0.458), and baseline pefr (p=0.400). 12 and 24 hours after treatment, significant increase in pefr in the nb and op groups were observed (p=0.032 and 0.008; respectively). the upward trend of pefr in nb group was significantly better than that of op group during 24 hours of treatment (p=0.005). vital signs and vbg results showed no significant differences between the two groups during the studied time interval. conclusion: nb, compared to op, could more effectively increase pefr and ameliorate disease severity of patients with copd exacerbation at 12 and 24 hours after treatment in ed. keywords: budesonide; drug administration routes; emergency service, hospital; nebulizers and vaporizers; peak expiratory flow rate; prednisolone; pulmonary disease, chronic obstructive cite this article as: aghili m, vahidi e, mohammadrezaei n, mirrajei t, abedini a. effectivness of nebulized budesonide for copd exacerbation management in emergency department; a randomized clinical trial. arch acad emerg med. 2020; 8(1): e85. 1. introduction american thoracic society/european respiratory society (ats/ers) guidelines defined chronic obstructive pulmonary disease (copd) as an irreversible and progressive airflow limitation. it is now the fourth leading cause of death in the world (1). copd causes a significant disease burden based on its severity and clinical course (2). systemic corticosteroids (scs) and inhaled corticosteroids ∗corresponding author: elnaz vahidi; department of emergency medicine, shariati hospital, tehran university of medical sciences, tehran, iran. tel: +989125948762; email: evahidi62@yahoo.com, e-vahidi@sina.tums.ac.ir (ics) have been endorsed by medical societies in the treatment of acute exacerbation of chronic copd since a long time ago (3, 4). corticosteroid consumption is recommended in addition to bronchodilator, oxygen, and antibiotic treatment in moderate to severe copd (5). despite its proven benefits, there are still concerns regarding acute and chronic adverse effects of scs (6, 7). hyperglycemia, myopathy, osteoporosis, and adrenal gland suppression are mentioned as significant concerns (8). in this regard, ics seems to be a more exciting option due to having fewer undesirable effects. nebulized corticosteroid (ncs) has been safely used as a substitute for ics since the last decade (8, 9). its consumption leads to changes in gas exchange parameters, which is believed to be due to its anti-inflammatory effects causing a dethis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. aghili et al. 2 crease in obstruction and airway resistance (9). some preliminary data suggest that ncs has similar efficacy to scs in management of copd cases, but still, further studies are needed, especially in the emergency setting. a review article in 2012 concluded that ncs could be used as a valuable alternative for ics in asthma and copd (10, 11). it also recommended additional research to confirm this promising role in the acute setting. nebulized budesonide (nb) is one of the most popular ncs that has been used in both asthma and copd, since a long time ago. this study aimed to compare the effectiveness of nb versus oral prednisolone (op) in increasing peak expiratory flow rate (pefr) of copd patients in emergency department (ed). 2. methods 2.1. study design and setting this double-blind, randomized clinical trial was performed in 3 general university hospitals (dr. shariati, imam khomeini and sina hospitals) during 6 months in 2019. patients with copd exacerbation, referring to ed were enrolled. in the first group, nb 0.5 mg every 30 minutes till three doses, placebo tablet, and standard treatment and in the second group, nebulized normal saline, op tablet 50 mg, and standard treatment were administered. pefr and vbg analysis of the two groups were compared during the first 24 hours after treatment. the study was approved by the ethics committee of tehran university of medical sciences (ethics code: ir.tums.medicine.rec.1397.108; irct id: irct20180523039800n1). the manuscript adheres to the “reporting of noninferiority and equivalence randomized trials: extension of the consort 2010 statement”. 2.2. participants all patients older than 18 years with moderate to severe copd exacerbation, referring to the eds of the mentioned hospitals were enrolled in our study. the eligibility criterion was having an established (pre-existing) diagnosis of copd, not the new probable cases. the diagnosis of copd exacerbation was established by an emergency physician (ep) as defined by ats/ers (1, 4). the exclusion criteria were: prior history of asthma, allergic rhinitis, interstitial lung disease, atopy, diabetes mellitus, hypertension, previous history of scs or ics consumption in the previous month, loss of consciousness, acute respiratory failure needing intubation and mechanical intubation, psychologic disorder, language barrier, or unwillingness to participate in our study. 2.3. interventions sampels were enrolled by block randomization (randon permuted block) of 4 (allocation ratio 1:1). randomisation was performed using unmarked, ordered, sealed envelopes. patients were randomly allocated to either the first group (nebulized budesonide (nb) 0.5 mg every 30 minutes till three doses (pulmicort respules® manufactured by astrazeneca lp), placebo tablet, and standard treatment) or the second group (nebulized normal saline every 30 min till three doses, op tablet 50 mg (manufactured by iran hormone), and standard treatment). standard treatment included: oxygen administration with the goal of oxygen saturation (spo2) > 90%, frequently inhaled β-agonist (salbutamol) via the metereddose inhaler (mdi) device, anticholinergic (ipratropium bromide) via mdi device (4 puffs every 20 min during the first hour and then continued by 2-4 puffs every 6 hours), and appropriate antibiotic selection. the acute treatment was started within 1 hour after patient admission. budesonide or normal saline was administered via a3 complete omron compressor nebulizer. the color and shape of studied drugs were the same in both groups. the chief investigator generated the random allocation sequence, and assigned and enrolled participants in each group. the triage nurse administered the specified drug with the proper method, route and dose of administration a previously prepared. the ep on each shift evaluated the patient, assessed outcoms and filled the checklist. ep, triage nurse, and patient were all blinded to the study. 2.4. data gathering demographic data, patient satisfaction, and disposition were recorded. vital signs, venous blood gas (vbg) parameters (partial pressure of oxygen (po2), partial pressure of carbon dioxide (pco2) and potential hydrogen (ph)), and pefr were assessed and documented at 0, 30, 60 min and 3, 6, 12 and 24 hours after admission. measurement of arterial blood gas is not the mainstay of ed evaluation in copd anymore. response to therapy can be easily monitored sufficiently by the patient’s clinical status, pulse oximetry, and vbg, if necessary. patient and physician satisfaction were evaluated based on the objective response to treatment on a scale from 0 (the worst) to 3 (the best). 2.5. primary and secondary endpoints our primary endpoint was comparing pefr before and after the treatment between the two groups. our secondary endpoints were comparisons of vbg parameters, vital signs, patient satisfaction, and disposition between the two groups. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e85 figure 1: flow diagram of the study. 2.6. statistical analysis all patients fulfilling the inclusion critera during the studied 6-month interval were enrolled in this study. a sample size of 40 patients in each group was calculated by considering; α: 0.05, β: 0.20, θ1-θ2: 0.1 (0.1 liter difference in fev1 between the two treatment regimens) based on reference (8), r:1 and δ: 0.1. to compare baseline values, pearson’s chi-square test (for qualitative variables) and independent t-test (for quantitative variables) were used. for comparison of changes in parameters between and within groups, the repeated measures analysis of variance (anova) test was used. the data were analyzed using spss version 22.0 (spss inc.). the mean values and 95% confidence intervals (cis) in each group were calculated. a p-value of <0.05 was considered significant. 3. results 3.1. baseline characteristics of studied patients finally, 43 patients in the first group (nb) and 41 patients in the second group (op) were included (figure 1). table 1 comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. aghili et al. 4 figure 2: peak expiratory flow rate (pefr), oxygen saturation (spo2), partial pressure of oxygen (po2), and partial pressure of carbon dioxide (pco2) changes during the studied time interval in both oral prednisolone (op) and nebulized budesonide (nb) groups. pares the patients’ baseline characteristics between groups. the two groups had similar age (p=0.544) and gender (p =0.984) distribution, duration of illness (p =0.458), and baseline pefr (p =0.400) and vbg analysis (p>0.05). 3.2. outcomes table 2 compares the vital signs and vbg parameters of patients at different times of evaluation between the two groups. pefr 12 (p = 0.032) and 24 (p = 0.008) hours after treatment were the only variables that were significantly different between groups. 3.3. pefr pefr had significantly increased from the baseline within each group 24 hours after the treatment (p= 0.024 in the nb group and 0.001 in the op group). comparing the two groups’ data showed that pefrs at 12 and 24 hours after the treatment had improved more significantly in the nb compared to the op group (p= 0.032 and 0.008; respectively). pefr assessment during the studied time interval disclosed that the upward trend of pefr was more significant in the nb compared to the op group (p= 0.005) (figure 2). 3.4. spo2 spo2 results at 24 hours after the treatment were increased from the baseline in both groups. however, this difference was significant only in the op group (p= 0.108 in the nb group and 0.001 in the op group). a comparison of the spo2 trend showed no significant difference between the two groups during the studied time interval (p= 0.887) (figure 2). 3.5. po2 po2 results at 24 hours after the treatment were increased from the baseline within both groups (p= 0.001 in both groups). a comparison of the po2 trend showed no significant difference between the two groups during the studied time interval (p= 0.574) (figure 2). 3.6. pco2 pco2 results at 24 hours after the treatment were decreased from the baseline in both groups. however, this difference was significant only in the op group (p= 0.073 in the nb this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e85 table 1: comparison of patients’ baseline characteristics between nebulized budesonide (nb) and oral prednisolone (op) groups variable nb (n = 43) op (n = 41) p-value age (years) mean ± sd 64.47±10.53 66.11±10.22 0.544 gender n (%) male 34 (79.0) 32 (78.0) 0.984 female 9 (21.0) 9 (22.0) duration of disease (years) mean ± sd 6.40 ± 4.91 5.56 ± 3.30 0.458 smoking duration (years) mean ± sd 32.08 ± 13.73 26.50 ± 12.69 0.135 pefr (%) mean ± sd 35.18±12.83 32.67±9.76 0.400 spo2 (%) mean ± sd 84.97±9.96 83.75±9.79 0.633 pulse rate (/minutes) mean ± sd 92.27±14.42 100.89±16.40 0.363 respiratoty rate (/minutes) mean ± sd 22.88±5.50 23.93±7.60 0.535 po2 (mmhg) mean ± sd 45.59±13.22 46.86±14.80 0.726 pco2 (mmhg) mean ± sd 56.49±13.72 54.72±9.13 0.622 ph mean ± sd 7.35±0.06 7.34±0.05 0.460 standard deviation (sd), peak expiratory flow rate (pefr), oxygen saturation (spo2), partial pressure of oxygen (po2) (normal range: 30-40), partial pressure of carbon dioxide (pco2) (normal range: 41-51), potential hydrogen (ph) (normal range: 7.31-7.41). group and 0.015 in the op group). a comparison of the pco2 trend showed no significant difference between the two groups during the studied time interval (p= 0.619) (figure 2). 3.7. patient and physician satisfaction patient and physician satisfaction with the treatment process were evaluated and graded from the worst (0) to the best (3). patient satisfaction had a mean score of 1.81±1.01 in the nb group and 1.88±0.88 in the op group (p= 0.876). physician satisfaction had a mean score of 1.82±1.06 in the nb group and 1.69±0.97 in the op group (p= 0.643). the ultimate disposition of patients was evaluated in 27 patients in the nb group and 24 cases in the op group. it was determined that 18 cases (66.6%) in the nb group needed hospital admission longer than a day, and 9 cases (33.4%) were discharged after 24 hours. in the op group, 23 patients (95.8%) were admitted to the hospital ward, and only one patient (4.2%) was discharged after 24 hours (p= 0.012). 4. discussion in the present study, it was determined that during the acute phase of copd exacerbation in ed, nb was more effective than op at 12 and 24 hours. it reduced copd severity (based on pefr) at 12 and 24 hours after the treatment, more than op. we observed the upward trend of pefr, and we found that this increasing trend was more significant in the nb group compared to the op group. vbg parameters were all changed for the better during disease recovery. however, their trend was not significantly different between the two groups. our results also stated that more patients in the op group were admitted to the hospital and needed more definite care after 24 hours, while in the nb group, more patients were discharged after a day. gunen et al. in 2007, studied severe copd patients (12). they administered the standard treatment (bronchodilator) alone to group 1, op+bronchodilator to group 2, and nb+bronchodilator to group 3. op was administered as 40 mg intravenous solution, and nb was administered every 6 hours at a dose of 0.5 mg/2 ml. cases were hospitalized for more than ten days and received the exact dose mentioned. they evaluated patients for a longer time during follow-up, and they found that at 24 and 72 hours and seven days, much better results and recovery were observed in groups 2 and 3. they also showed that after ten days, more patients in group 1 were discharged from the hospital compared to the other two groups. finally, they concluded that in the acute phase, the recovery rates with regards to spirometry and arterial blood gas parameters did not differ between the groups utilizing some form of corticosteroid. however, recovery rates in this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. aghili et al. 6 table 2: comparison of vital signs and venus blood gas (vbg) parameters between nebulized budesonide (nb) and oral prednisolone (op) groups variable time(hour) nb (n = 43) op (n = 41) p-value mean±sd 95%ci mean±sd 95%ci pefr (%) 0 35.18±12.83 18.33-75.0 32.67±9.76 20.59-59.94 0.400 0.5 37.33±13.17 18.33-75.0 34.36±11.03 23.15-65.42 0.349 1 38.91±14.34 17.50-80.77 35.65±11.55 24.07-67.29 0.346 3 40.02±14.43 18.33-76.92 37.31±11.73 25.0-67.29 0.458 6 40.44±13.47 20.18-63.64 35.52±8.92 23.53-59.72 0.175 12 42.09±12.0 24.0-61.0 33.58±7.32 24.0-48.0 0.032 24 44.43±9.38 28.70-60.34 33.13±6.40 25.41-49.32 0.008 variable time mean±sd range mean±sd range p-value spo2 (%) 0 84.97±9.96 52-96 83.75±9.79 50-96 0.633 0.5 90.22±6.56 68-99 89.48±6.11 70-98 0.654 1 92.10±5.24 74-98 90.64±6.11 73-98 0.331 3 92.52±4.98 78-98 91.76±5.22 75-97 0.594 6 91.14±4.51 82-97 91.35±4.94 79-98 0.889 12 90.17±5.81 78-97 91.40±4.34 80-98 0.533 24 92.20±3.05 87-96 92.42±2.68 87-96 0.861 pr(/min) 0 92.27±14.42 70-127 100.89±16.40 62-130 0.363 0.5 94.09±11.43 72-120 96.79±13.74 61-125 0.411 1 91.03±10.67 73-118 93.30±13.77 65-127 0.484 3 87.81±8.46 75-103 92.40±12.15 70-120 0.118 6 88.95±8.33 88.0-108 91.30±9.83 78-116 0.414 12 87.92±3.06 85-94 87.53±7.48 75-100 0.859 24 86.10±4.70 80-95 86.92±6.36 78-97 0.740 rr(/min) 0 22.88±5.50 16-35 23.93±7.60 14-48 0.535 0.5 21.60±4.43 15-33 22.43±6.05 13-40 0.541 1 20.81±4.45 15-31 20.74±5.44 15-39 0.960 3 19.85±4.74 15-32 19.48±4.12 14-30 0.765 6 20.38±5.43 14-32 19.65±4.15 15-32 0.632 12 20.33±3.65 16-28 19.27±3.47 15-30 0.446 24 18.50±1.35 16-21 18.67±2.01 15-21 0.826 po2 (mmhg) 0 45.59±13.22 20-74 46.86±14.80 15-91 0.726 0.5 49.08±15.53 22-84 54.73±12.63 34-84 0.138 1 49.99±14.62 16-80 55.97±12.77 35-93 0.108 3 50.68±13.66 25-72 55.18±12.51 31-85 0.230 6 55.20±12.84 25-75 59.01±10.54 37-78 0.311 12 59.15±17.64 21-78 63.50±9.80 39-80 0.436 24 67.45±5.79 57-76 65.95±8.70 51-85 0.647 pco2 (mmhg) 0 56.49±13.72 29-89 54.72±9.13 24-88 0.622 0.5 52.64±9.87 39-71 53.49±14.01 26-85 0.792 1 52.72±11.14 31-76 51.50±12.17 31-85 0.695 3 51.73±11.37 32-78 48.71±10.63 31-75 0.337 6 52.94±11.12 37-71 51.46±10.10 39-73 0.662 12 53.18±11.82 38-71 52.15±11.52 34-70 0.824 24 54.49±11.07 40-71 50.96±10.52 32-65 0.453 data are presented as mean ± standard deviation with 95% confidence interval (ci) or range. peak expiratory flow rate (pefr), oxygen saturation (spo2), pulse rate (pr), reapiratory rate (rr), partial pressure of oxygen (po2), partial pressure of carbon dioxide (pco2), potential hydrogen (ph). these groups were significantly better than that of the group receiving only bronchodilator treatment. maltais et al. in 2002, performed a multicenter, doubleblind, randomized placebo-controlled trial on 199 patients with copd exacerbation (8). they compared nb, op, and placebo in 3 different groups. 2 mg nb was administered every 6 hours in group 1, 30 mg op tablet was administered every 12 hours in group 2, and finally, the specified placebo was ordered in group 3. all patients received the standard treatment. patients were evaluated from baseline to 72 hours after drug administration, and they had a follow-up of 10 days. their results determined that the use of nb and op was assothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 7 archives of academic emergency medicine. 2020; 8(1): e85 ciated with a faster rate of improvement in spirometry compared with placebo. less adverse effects were observed in group 1. they suggested that nb might be an alternative to op for the treatment of acute nonacidotic exacerbation of copd. mirici et al. in 2003, analyzed 44 patients with copd exacerbation (9). they either received 40 mg parenteral prednisolone or 4 mg nb every 12 hours. they evaluated pefr and arterial blood gas parameters at 30 min, 6, 12, 24, and 48 hours and also day 10. they demonstrated that there were significant increases in pefr, po2, and spo2 values within the groups. no significant differences were observed between the groups about the percentage of changes in pefr, po2, and spo2 values during the entire period of assessment. icss are the mainstay of anti-inflammatory treatment in asthma and copd. melani et al. in 2012, reviewed 16 clinical trials on asthma and copd and concluded that ncs is currently a valid alternative to inhalers in asthma and copd. they recommended further research to confirm the promising role of ncs in acute settings (13). guade et al. in 2012 reviewed eight previous studies comparing ncs vs. scs (10). in all of their included studies, nb had been used in acute exacerbation of copd in different dosages, and it had been compared with either parental or oral scs. all the studies had confirmed the clinical efficacy of nb to be of similar extent to that of scs. they also recommended more extensive studies to be designed and done. rodrigo, in 2006, published a review article in the chest journal and evaluated the rapid effects of ics in acute asthma (11). their data showed that ics could have early beneficial effects (even 1 to 2 h), especially when used in multiple frequent doses and administered in short time intervals. the nongenomic effect was said to be a possible contributor to the clinical effects of corticosteroids. the current study confirmed that nb, when administered at frequent doses (0.5 mg) at shorter time intervals (every 30 min) up to 3 doses, could more significantly increase copd patients’ pefr at 12 and 24 hours compared to op. this method of administration showed us that we could discharge more patients in a shorter time. 5. limitations the sample size is small so the generalizability of the results is one of our limitations. further studies with larger sample size are required to determine the exact effect of nb on copd exacerbation. frequent assessment by pefr and vbg was time-consuming, and some patients got tired of frequent assessments. we did not evaluate patients’ current medications or previous intensive care unit admissions (baseline disease burden). 6. conclusion nb was more effective than op in increasing pefr at 12 and 24 hours in copd exacerbation and, in the acute phase, nb could ameliorate copd severity more efficiently compared to op. 7. declarations 7.1. acknowledgement none. 7.2. author contribution aa and ev conceived the study, designed the trial, supervised the conduct of the trial and data collection. ma and tm undertook recruitment of participating centers and patients and managed the data, including quality control. nm and ev provided statistical advice on study design and analyzed the data. ev drafted the manuscript, and all authors contributed substantially to its revision. ev takes responsibility for the paper as a whole. 7.3. funding/support none. 7.4. conflict of interest none. references 1. celli br, decramer m, wedzicha ja, wilson kc, agustí a, criner gj, et al. an official american thoracic society/european respiratory society statement: research questions in chronic obstructive pulmonary disease. american journal of respiratory and critical care medicine. 2015;191(7):e4-e27. 2. minas m, dimitropoulos k, pastaka c, papadopoulos d, markoulis n, gourgoulianis k. global initiative for chronic obstructive lung disease for chronic obstructive pulmonary disease: gold opportunity for lung disorders. preventive medicine. 2005;40(3):274-7. 3. vestbo j, hurd ss, agustí ag, jones pw, vogelmeier c, anzueto a, et al. global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: gold executive summary. american journal of respiratory and critical care medicine. 2013;187(4):347-65. 4. patel ar, patel ar, singh s, singh s, khawaja i. global initiative for chronic obstructive lung disease: the changes made. cureus. 2019;11(6). 5. health nio. national heart, lung and blood institute: global initiative for asthma. global strategy for asthma this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem m. aghili et al. 8 management and prevention (www ginasthma com). 2002. 6. henzen c, suter a, lerch e, urbinelli r, schorno xh, briner va. suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. the lancet. 2000;355(9203):542-5. 7. walsh l, wong c, oborne j, cooper s, lewis s, pringle m, et al. adverse effects of oral corticosteroids in relation to dose in patients with lung disease. thorax. 2001;56(4):279-84. 8. maltais fo, ostinelli j, bourbeau j, tonnel ab, jacquemet n, haddon j, et al. comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. american journal of respiratory and critical care medicine. 2002;165(5):698-703. 9. mirici a, meral m, akgun m. comparison of the efficacy of nebulised budesonide with parenteral corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease. clinical drug investigation. 2003;23(1):55-62. 10. gaude g, nadagouda s. nebulized corticosteroids in the management of acute exacerbation of copd. lung india: official organ of indian chest society. 2010;27(4):230. 11. rodrigo gj. rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. chest. 2006;130(5):1301-11. 12. gunen h, hacievliyagil ss, yetkin o, gulbas g, mutlu l, in e. the role of nebulised budesonide in the treatment of exacerbations of copd. european respiratory journal. 2007;29(4):660-7. 13. melani as. nebulized corticosteroids in asthma and copd. an italian appraisal. respiratory care. 2012;57(7):1161-74. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitations conclusion declarations references emergency. 2018; 6(1): e53 or i g i n a l re s e a rc h intravenous versus subcutaneous midazolam using jetinjector in pediatric sedation; a randomized clinical trial majid hajimaghsoudi1, mehdi bagherabadi2, ehsan zarepur3, vahid ahmadi hanzaei4∗ 1. emergency department, trauma research center, shahid sadoughi university of medical sciences, yazd, iran. 2. emergency department, school of medicine, shahid sadoughi university of medical sciences, yazd, iran. 3. isfahan cardiovascular research center, cardiovascular research institute, isfahan university of medical sciences, isfahan, iran. 4. emergency department, school of medicine, shahid sadoughi university of medical sciences, yazd, iran. received: may 2018; accepted: august 2018; published online: 31 august 2018 abstract: introduction: the quality of interventions in children is largely dependent on their control. hence, this study compared the sedative effects of subcutaneous (sc) and intravenous (iv ) midazolam in pediatric sedation induction. methods: this randomized clinical trial was conducted on children aged 1-6 years presenting to emergency departments of shahid sadoughi and shahid rahnemoon hospitals, yazd, iran. participants were randomly assigned to iv or sc midazolam using a jet injector and success rate, degree of sedation, and satisfaction of parents and physician were compared between groups. results: 60 cases with the mean age of 3.15±1.43 (1-6) years were randomly assigned to the sc (30 cases) or iv (30 cases) groups (56.7% female). sc and iv groups were similar regarding the mean age (p = 0.165) and sex (p = 0.121). depth of sedation (p=0.900), control of child (p=0.711), in-charge physician’s satisfaction (p=0.467), successful sedation and need for rescue dose (p=0.519) were not different between groups. iv midazolam group had a significantly shorter recovery time (about 10 minutes; p=0.040) and sc midazolam group had a significantly higher level of parent satisfaction (p=0.001). conclusion: the findings indicate no significant difference in depth of sedation, control of child, in-charge physician’s satisfaction, successful sedation (reaching stage 1 of sedation or higher), and need for rescue dose of sc and iv midazolam. parents’ satisfaction was significantly greater with sc administration and iv injection had shorter recovery time. keywords: midazolam; sedation; jet injector; injections, subcutaneous; personal satisfaction; children. © copyright (2018) shahid beheshti university of medical sciences cite this article as: hajimaghsoudi m, bagherabadi m, zarepur e, ahmadi hanzaei v. intravenous versus subcutaneous midazolam using jet-injector in pediatric sedation; a randomized clinical trial. emergency. 2018; 6(1): e53. 1. introduction m any patients present to the emergency department (ed). children are vulnerable to many diseases and constitute a considerable number of traumatic patients presenting to ed. the correct implementation of diagnostic procedures requires control and tranquility of children as lack of children’s cooperation due to anxiety and discomfort leads to lengthening of diagnostic procedures and reduces their quality. so, the use of sedatives is mandatory ∗corresponding author: vahid ahmadi hanzaei; emergency medicine department, shahid sadoughi hospital, ibn sina st., riazi sq., po box 8915887857, yazd, iran. e-mail: d.vahidahmadi@yahoo.com tel: +98 3538224000 fax: +98 3538224001 in younger children to increase the quality of the provided interventions and shorten the duration of these procedures. the use of diagnostic procedures and minor surgical operations outside the operating room has increased over the last decade. yet, the administration of sedatives to children is associated with risks like hypoventilation, apnea, airway obstruction, laryngospasm, and impaired cardiopulmonary functioning. hence, the selection of appropriate drugs for diagnostic and therapeutic interventions is as important as the diplomacy and tactfulness of the in-charge physician in reacting to drug complications (1-5). midazolam is a shortacting benzodiazepine with sedative, narcotic, anxiolytic, anticonvulsive, and relaxing effects (1, 6, 7). its acute complications include respiratory suppression and apnea which occur rarely in cases of rapid injection of high doses of the drug. adthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. hajimaghsoudi et al. 2 ditionally, midazolam is a rapid-acting sedative with minimal effect on blood oxygenation level and cerebral blood flow, which renders it a suitable drug for cerebral imaging studies like mri (6). midazolam can be administered via intravenous (iv ), subcutaneous (sc), muscular, intranasal, buccal, and rectal routes. one modality of midazolam administration is the subcutaneous injection in which the drug effect is initiated in 7 minutes reaching a peak during 23-49 minutes. the onset of iv midazolam effect is 3-5 min, which is finally eliminated by the liver (7, 8). given that the subcutaneous injection with a jet injector is almost painless, and also based on what has been said so far and considering the lack of sufficient related studies in this field, especially on the use of jet injector in ed (9-11), we embarked on comparing the sc midazolam using jet injector with iv midazolam in performing sedation for doing non-invasive diagnostic procedures in children aged 1-6 years. 2. methods 2.1. study design and setting this parallel randomized clinical trial was carried out on traumatized children aged 1-6 years presenting to eds of shahid sadoughi hospital and shahid rahnemoon hospitals in yazd, central iran, from april to june 2015, who needed control and sedation for undergoing a diagnostic procedure. the research goals and procedures were explained clearly to the parents and the possible complications of drug administration (hypoxia, respiratory depression, apnea, coma, hypotension, agitation, confusion, and cough) were elucidated in a crystal-clear fashion. informed written consent was obtained from the children’s parents. the research proposal was approved by committee of ethics in research at shahid sadoughi university of medical sciences, yazd, iran, with code of ethics no.: ir.ssu.medicine.rec.1393.30 and registered in iranian registry of clinical trials with no.: irct no.: irct201510018640n2. 2.2. participants traumatized children aged 1-6 years presenting to eds of the mentioned hospitals and in need of sedation for doing noninvasive diagnostic procedures were enrolled. un-stable vital signs, reduced level of consciousness, a positive history of taking anticonvulsive drugs, allergy to midazolam, lack of consent for participating in the study, and children with moderate to severe pain (pains with scores greater than 4 out of 10 form the researcher’s perspective) were among the exclusion criteria. 2.3. procedure and data gathering after history taking and complete medical examination, children diagnosed by the medical emergency specialist to be in need of sedation for performing diagnostic intervention who met the inclusion criteria were randomly and blindly (without awareness of the researcher and the assessor) assigned to sc or iv midazolam groups using convenience sampling method. in doing so, random numbers were selected by a computer and placed in opaque envelopes, which were numbered sequentially. the number in the envelope was placed in the sc with jet injector group if it was an even number and in the iv group if it was an odd number. injection was done in the brachial area for jet injector patients while iv injection was performed in the cubital zone after phlebotomy in the iv group. phlebotomy was performed by nurses with a 5-year work experience. if phlebotomy failed in the cubital area of one hand, the other hand was then used for injection. midazolam with the initial dose of 0.2 mg/kg was administered subcutaneously using jet injector (injext m 30, carpol 0.3 cc, needle free, made in germany) in the case group and given to the iv group with the dose of 0.1 mg/kg by a peripheral vein catheter. the assessor was also blind to the site of injection in both groups not to be aware of the type of injection. the children underwent cardiac monitoring and pulse oximetry before the onset of sedation and their level of consciousness was measured by the assessor once per min before and after sedation (stage 0: conscious; stage 1: silence; stage 2: drowsy; stage 3: napping; stage 4: deep sleep). when the child reached stage 1 of sedation, the intended procedure was commenced. successful sedation (achieving stage 1 of sedation), degree of sedation before and after injection (by the assessor once per min), and parents’ and the physician’s satisfaction with the whole process of sedation and diagnostic technique (completely dissatisfied, dissatisfied, indifferent, satisfied, and completely satisfied) were measured as primary variables. in addition, the time of regaining full consciousness (level a of avpu), child control, and the need for reinjection of drug in the case of failure were assessed as secondary variables. child control was defined as the degree of difficulty in positioning and controlling the child during performance of the procedure for which the physician was asked by the assessor using a 5-point likert scale item (very difficult, difficult, moderate, easy, and very easy). in cases that the child did not enter stage 1, reinjection was performed 20 minute after the first injection in the case group and 3 minute after the first injection in the control group. if after one reinjection the required sedation was not achieved, the procedure was considered as failure and the resident medical emergency specialist decided on the continuation or discontinuation of the procedure. the child was monitored during and after completion of the procedure till full consciousness was reached and the time of full consciousness recovery was measured. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6(1): e53 flowchart 1: enrollment and allocation of patients to the studied groups. 2.4. statistical analysis the sample volume in each group was set at 42 on the basis of the study by bennett et al. (12) considering type i error of 0.05 and type ii error of%20, which was increased to 60 to enhance the validity of the study results. the data were analyzed by an experienced statistician blind to the groups using spss ver. 17 (spss, chicago, il, usa). descriptive statistics of mean ± standard deviation and frequency (percentage) were used to report the results. also, chi-square test was used to analyze nominal data, and independent sample t-test or their nonparametric equivalents were used to analyze the quantitative data. the level of significance was considered 0.05. 3. results 3.1. baseline characteristics of participants 75 children were evaluated, 10 of which were excluded due to not meeting the inclusion criteria or declining to participate (flowchart 1). finally, 60 cases with the mean age of 3.15±1.43 years were randomly assigned into the sc (30 cases) or iv (30 cases) groups (56.7% female). owing to lack of cooperation, 1 child from the jet injector group and 2 children from the iv group were excluded from the study. also, 1 child was omitted from each group due to the parents of the two children deciding to withdraw from the study (flowchart 1). sc and iv groups were similar regarding the mean age (2.8 ± 1.2 vs 3.4 ± 1.6, respectively; p = 0.165) and sex (56.7% vs 36.7% female, respectively; p = 0.121). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. hajimaghsoudi et al. 4 table 1: comparing the procedural sedation and analgesia (psa) characteristics of subcutaneous and intravenous midazolam in 16 year old children psa characteristics subcutaneous n=30 intravenous n=30 p depth of sedation fully conscious 5 (16.7) 3 (10.0) silent 1 (3.5) 1 (3.3) drowsy 0 0 0.900 napping 1 (3.3) 1 (3.3) deep sleep 23 (76.7) 25 (83.3) child control very difficult 1 (3.3) difficult 4 (13.3) 5 (16.7) moderate 2 (6.7) 2 (6.7) 0 (0) easy 22 (73.3) 23 (76.6) very easy 1 (3.3) 0 (0) physicians’ satisfaction completely dissatisfied 4 (13.3) 4 (13.3) dissatisfied 3 (10) 1 (3.3) indifferent 1 (3.3) 0 (0) 0.467 satisfied 8 (26.7) 22 (73.3) completely satisfied 14 (46.7) 3 (10.0) parents’ satisfaction completely dissatisfied 3 (10.0) 4 (13.3) dissatisfied 2 (6.7) 7 (23.3) indifferent 3 (10.0) 12 (40.0) 0.001 satisfied 18 (60.0) 6 (20.0) completely satisfied 4 (13.3) 1 (3.3) successful sedation* yes 25 (83.3) 27 (90.0) 0.519 no 5 (16.7) 3 (10.0) recovery time (minute) mean ± standard deviation 35.8 ± 9.71 24.8 ± 7.60 0.040 data are presented as number (%). *: achieving sedation stage 1. 3.2. psa characteristics of two groups table 1 compares the characteristics of psa between sc and iv midazolam groups. two groups were similar regarding the depth of sedation (p=0.900), control of child (p=0.711), in-charge physician’s satisfaction (p=0.467), successful sedation and need for rescue dose (p=0.519). iv midazolam group had a significantly shorter recovery time (about 10 minutes; p=0.040) and sc midazolam group had significant higher level of parent satisfaction (p=0.001). none of the possible midazolam side effects (hypoxia, respiratory depression, apnea, coma, hypotension, agitation, confusion, and cough) were manifested in any child in this study. moreover, no dermal reaction like arythema, swelling, or inflammation was observed at the site of injection. 4. discussion the findings indicate no significant difference in depth of sedation, control of child, in-charge physician’s satisfaction, successful sedation (reaching stage 1 of sedation or higher), and need for rescue dose between sc and iv midazolam. parents’ satisfaction was significantly greater with sc administration and iv injection had shorter recovery time. the traumatized children ought to be controlled and immobilized during diagnostic procedures such as ct scanning, mri, radiography, and ultrasonography. there are various medications with different complications for induction of sedation. the study by pecking et al. (2002) conducted in france investigated the biological power of sc midazolam in volunteers and the results showed that the biological potency of sc injection of the drug was not significantly different from the iv injection so that when the iv route was not accessible, the sc route could be used safely, which is consistent with our findings (13). moreover, the study by greenberg et al. (1995) explored the effect of administration of different doses of midazolam with jet injector on 40 children and found that jet injector administration quickly induced the effect of midazolam. this is again consistent with our findings (14). the highly appropriate effect of the drug in the jet injector group may be attributed to proper distribution of the drug in the tissue leading to greatly acceptable absorption and the rapid effect of the drug (12). generally speaking, although in the this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 5 emergency. 2018; 6(1): e53 jet injector method it logically takes longer for the drug to show its effect compared to the iv method, in the studies conducted so far the effect of drug is seen faster when using jet injector compared to the oral route since administration of the drug using jet injector can induce the intended plasma level of midazolam with the same speed as the im injection of the drug. also, when there is oral route resistance in the child (15) or when there is the need for avoiding phlebotomy tension in the child, the use of jet injector is a suitable method. of course, the time of full recovery in jet injector group was 35.8âś9.71 minute, which was significantly higher compared to the iv group. this can be viewed as a weak point of the method. the study by bennett et al. (1998) conducted in usa investigated the effect of sc midazolam with needle and syringe compared to the sc injection of this drug using jet injector. the findings of the mentioned clinical trial conducted on 14 children suggested that the discomfort caused by subcutaneous midazolam in the jet injector group was less compared to the needle and syringe group though the difference between the two was not significant. finally, they concluded that the peak plasma level was achieved more rapidly with jet injector probably due to the distribution of the medicine in the tissue by the jet injector (12). our findings also suggested that the parents were significantly more satisfied with jet injector method. in the study by bennett et al., the rate of discomfort was smaller with jet injector, though the difference was not significant due to small sample volume (14 samples) or the study design (12). overall, parents were more satisfied with the jet injector method while physicians were less satisfied with this route. it appears that the child sustains less pain and discomfort with the jet injector route causing more satisfaction among the parents; nonetheless, physicians are more satisfied with the iv method since the drug exerts its effect more rapidly leading to faster sedation. however, our results demonstrated that the physicians in the jet injector group assessed child controlling and positioning of 23 (%76.6) children as easy and very easy during the procedure. the same was true with the iv group indicating another positive factor in the jet injector method compared to the iv route. considering the complications of midazolam (hypoxia, respiratory depression, apnea, coma, hypotension, agitation, confusion, and cough), none of these undesirable side effects were manifested in any child in this study. moreover, no dermal reaction like erythema, swelling, or inflammation was observed in the site of injection, a finding which is consistent with the results obtained by bennett who reported no specific complication in 14 adult patients who underwent sc midazolam injection with jet injector compared to subcutaneous needle and syringe iv injection (12). also, the results of the study by domino et al. (1998) showed that the sc injection of midazolam with jet injector was associated with appropriate effect (16). it seems that sc injection using jet injector as a wellknown old method could be considered as an alternative root for induction of sedation in pediatric non-invasive diagnostic procedure. considering the need that is felt for a painless, safe, and rapid-acting method, jet injector as a needleless injection system can serve as an effective tool with little complications to be used for inducing sedation, especially in stressful situations like ed that demands more tranquility. it is suggested that future studies investigate other aspects of these two methods such as comparison of the resulted infection or dermal complications in a longer time interval after injection. different jet injectors may be applied for various age groups or greater carpols may be used with jet injectors. additionally, jet injector may be explored for induction of anesthesia or sedation in painful or invasive procedures. a combination of the main drug with local anesthetics along with their merits and demerits is also suggested. 5. limitation the children could not be made blind to the study due to the nature of the use of jet injector. there was no placebo due to ethical considerations to avoid pain in the children. 6. conclusion the findings indicate no significant difference in depth of sedation, control of child, in-charge physician satisfaction, success rate of sedation (reaching stage 1 of sedation or higher), and need for rescue dose between sc and iv midazolam. parents’ satisfaction was significantly greater with sc administration and iv injection had shorter recovery time. 7. appendix 7.1. acknowledgements the authors give their special thanks to all the staff in eds of shahid sadoughi and shahid rahnemoon hospitals in yazd and also all the children and their parents. the manuscript was extracted from a medical emergency residency thesis by vahid ahmadi hanzaei. 7.2. authors’ contribution all authors contributed to this project and article almost equally. all authors read and approved the final manuscript. 7.3. funding/support none. 7.4. conflict of interest all authors declare that they have no conflicts of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com m. hajimaghsoudi et al. 6 references 1. hijazi om, ahmed ae, anazi ja, al-hashemi he, aljeraisy mi. chloral hydrate versus midazolam as sedative agents for diagnostic procedures in children. saudi med j. 2014;35(2):123-31. 2. cote c, wilson s. guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update. pediatrics. 2006;118(6):2587-602. 3. imanian m, ghasemzadeh mj, zarepur e, zarepur a, farahani rs, farahani rs. the relationship between pneumonia with parental smoking in children under 10 year old: a casecontrol study. int j pediatr-masshad. 2018;6(6):7791-6. 4. sasannejad p, rezaei f, bidaki r, zarepur e. rare presentation of moyamoya disease with sub acute presentation in iran. iran j child neurol. 2018;12(1):89-93. 5. jafari m, biuki aa, hajimaghsoudi m, bagherabadi m, zarepur e. intravenous haloperidol versus midazolam in management of conversion disorder; a randomized clinical trial. emergency.6(1):43. 6. khurmi n, patel p, kraus m, trentman t. pharmacologic considerations for pediatric sedation and anesthesia outside the operating room: a review for anesthesia and non-anesthesia providers. paediatr drugs. 2017;19(5):435-46. 7. martinez jl, sutters ka, waite s, davis j, medina e, montano n, et al. a comparison of oral diazepam versus midazolam, administered with intravenous meperidine, as premedication to sedation for pediatric endoscopy. j pediatr gastroenterol nutr. 2002;35(1):51-8. 8. fallah r, fadavi n, behdad s, fallah tafti m. efficacy of chloral hydrate-hydroxyzine and chloral hydratemidazolam in pediatric magnetic resonance imaging sedation. iran j child neurol. 2014;8(2):11-7. 9. playfor s, jenkins i, boyles c, choonara i, davies g, haywood t, et al. consensus guidelines on sedation and analgesia in critically ill children. intensive care med. 2006;32(8):1125-36. 10. hajimaghsoudi m, vahidi e, momeni m, arabinejhad a, saeedi m. comparison of local anesthetic effect of lidocaine by jet injection vs needle infiltration in lumbar puncture. am j emerg med. 2016;34(7):1225-9. 11. luhmann jd, kennedy rm, porter fl, miller jp, jaffe dm. a randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. ann emerg med. 2001;37(1):20-7. 12. bennett j, nichols f, rosenblum m, condry j. subcutaneous administration of midazolam: a comparison of the bioject jet injector with the conventional syringe and needle. j oral maxillofac surg. 1998;56(11):1249-54. 13. pecking m, montestruc f, marquet p, wodey e, homery mc, dostert p. absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers. br j clin pharmacol. 2002;54(4):357-62. 14. greenberg rs, maxwell lg, zahurak m, yaster m. preanesthetic medication of children with midazolam using the biojector jet injector. anesthesiology. 1995;83(2):2649. 15. fine b, castillo r, mcdonald t, paisansathan c, zsigmond e, hoffman we. jet injector compared with oral midazolam for preoperative sedation in children. paediatr anaesth. 2004;14(9):739-43. 16. domino ef, zsigmoid ek, kovacs v, olajos b, fekete g. a new route, jet injection for anesthetic induction in children. iv. midazolam plasma levels. int j clin pharmacol ther. 1998;36(8):458-62. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction methods results discussion limitation conclusion appendix references archives of academic emergency medicine. 2020; 8(1): e67 rev i ew art i c l e extracorporeal hemoperfusion as a potential therapeutic option for severe covid-19 patients; a narrative review saeid safari1∗, alireza salimi2, alireza zali1, alireza jahangirifard3, ehsan bastanhagh4, reza aminnejad2,5, ali dabbagh6, amir hossein lotfi 7, mohammad saeidi5 1. functional neurosurgery research center, shohada tajrish neurosurgical comprehensive center of excellence, shahid beheshti university of medical sciences, tehran, iran. 2. department of anesthesiology and critical care, shahid beheshti university of medical sciences, tehran, iran. 3. chronic respiratory disease research center, national research institute of tuberculosis and lung diseases (nritld), shahid beheshti university of medical sciences, tehran, iran. 4. department of anesthesiology and critical care, tehran university of medical sciences, tehran, iran. 5. department of anesthesiology and critical care, qom university of medical sciences, qom, iran. 6. anesthesiology research center, shahid beheshti university of medical sciences, tehran, iran. 7. department of intensive care, laleh hospital, tehran, iran. received: july 2020; accepted: july 2020; published online: 22 august 2020 abstract: the 2019 novel coronavirus (officially known as severe acute respiratory syndrome coronavirus 2, sars-cov2) was first found in wuhan, china. on february 11, 2020, the world health organization (who) has declared the outbreak of the disease caused by sars-cov2, named coronavirus disease 2019 (covid-19), as an emergency of international concern. based on the current epidemiological surveys, some covid-19 patients with severe infection gradually develop impairment of the respiratory system, acute kidney injury (aki), multiple organ failure, and ultimately, death. currently, there is no established pharmacotherapy available for covid-19. as seen in influenza, immune damage mediated by excessive production of inflammatory mediators contributes to high incidence of complications and poor prognosis. thus, removal or blocking the overproduction of these mediators potentially aids in reducing the deleterious cytokine storm and improving critically ill patients’ outcomes. based on previous experience of blood purification to treat cytokine storm syndrome (css) in severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers), here we aimed to review the current literature on extracorporeal hemoperfusion as a potential therapeutic option for css-associated conditions, with a focus on severe covid-19. keywords: covid-19; cytokine release syndrome; respiratory distress syndrome, adult; hemoperfusion cite this article as: safari s,salimi a, zali a, jahangirifard a, bastanhagh e, aminnejad r, dabbagh a, lotfi a h, saeidi m. extracorporeal hemoperfusion as a potential therapeutic option for severe covid-19 patients; a narrative review. arch acad emerg mede. 2020; 8(1): e67. 1. introduction coronavirus disease 2019 (covid-19) is a newly recognized zoonotic respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). it has already affected millions of people worldwide, accounting for a significant morbidity and mortality burden. early studies, ∗corresponding author: saeid safari; functional neurosurgery research center, shohada tajrish neurosurgical comprehensive center of excellence, shahid beheshti university of medical sciences, tehran, iran. email: drsafari.s@gmail.com, phone: 09392117300 mostly coming from china, have reported that more than 20% of critically ill covid-19 patients with pneumonia, required admission to the intensive care unit (icu) (1). moreover, a significant number of critical cases were reported to develop multiple organ dysfunction syndrome (mods) and acute respiratory distress syndrome (ards), resulting in death within a short time (1, 2). a prominent modulator of sepsis, ards, and organ damage in critical care patients is "cytokine storm syndrome" (css) caused by dysregulated inflammatory response, in either the absence or presence of a pathogenic microorganism. localized inflammation is a normal, necessary defense and repair this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. safari et al. 2 response of body to injury or infection. this process is triggered when innate immune cells detect infection or tissue injury. upon activation, immune cells release various proinflammatory cytokines including il-1, 6, 8, 11, 12, interferon y and tnf-α. such pro-inflammatory response promotes production of macrophages, enhances vascular permeability, promotes coagulation, and activates extravasation of neutrophils into infected tissue. in order to restore the body homeostasis, once the pro-inflammatory stimulus is eradicated, an anti-inflammatory response (e.g. production of il-1ra, il-4, and il-10) is essential to reduce the overall production of inflammatory cytokines (3). thus, a tightly regulated self-limited protective response controls acute inflammation. however, in many life-threatening conditions such as sepsis, trauma, burn injury, severe lung injury, liver failure, pancreatitis, influenza and cytokine release syndrome, the pro/anti-inflammatory response balance is dysregulated. if homeostasis is not restored, uncontrolled pro-inflammatory response along with an unbalanced anti-inflammatory feedback causes production of excess inflammatory mediators, particularly cytokines (3). cytokines are a family of immunoregulatory molecules that play roles in regulation of pro and anti-inflammatory responses. their family includes chemokines, interferons, interleukins, lymphokines, tumor necrosis factor and many others. overproduction of these inflammatory mediators (css) induces severe vascular injuries, increased vascular permeability, and immense plasma leakage, leading to edema, necrosis, and cell death. these events ultimately lead to clinical symptoms including, high fever, accumulation of leukocytes and formation of blood clots in micro-vessels, hypotension, hemoconcentration, increased oxygen demand, acidosis, pulmonary edema, alveolar hemorrhage, and pleural effusion. two common clinical sequels to css are ards and mods. 2. css in severe covid-19 the term "cytokine storm" in viral infection was first used in 2000, in an investigation on cytomegalovirus (4). soon after, it began to appear more frequently in the scientific literature, showing an association with a wide variety of viral infections including epstein-barr virus (5), group a streptococcus (6), influenza virus (7), variola virus (8), and severe acute respiratory syndrome coronavirus (sars-cov ) (9)(10), mers-cov (11), h5n1 and h1n1 influenza viruses (12, 13). similar to that of sars and mers, laboratory findings and clinical manifestations of some critical covid-19 patients suggest a strong role for the involvement of css and pathophysiological sequelae (14). for instance, elevated levels of several inflammation-related biomarkers, including creactive protein (crp), ferroprotein, and erythrocyte sedimentation rate (esr) and interleukin-6 (il-6) were reported in patients with covid-19 pneumonia (1). moreover, increased levels of interleukin-2 (il-2), interleukin-7 (il-7), interleukin-10 (il-10) , granulocyte colony-stimulating factor (gscf), interferon gamma-induced protein 10 (ip-10), chemokine (c-c motif ) ligand 2 (ccl2), chemokine (c-c motif ) ligand 3 (ccl3), and tumor necrosis factor α (tnfîś) in patients admitted to icu compared to non-icu patients suggests that they are related to poor prognosis (15, 16). meanwhile, elevated levels of inflammatory indicators in the blood of covid-19 patients are suggested to be among predictors of a fatal outcome (17). building on previous experience from sars and mers, reducing viral load by antiretroviral therapy and modulating inflammatory responses via pharmacological agents appear to be effective measures to improve the prognosis of sarscov-2 infection (18-20). in organ dysfunction syndromes, when pharmacological treatment is not sufficiently effective or available, advanced methods of treatment such as mechanical ventilation and hemodynamic support are the only substitutional therapeutic strategies. accordingly, immunomodulatory strategies, cytokine antagonists, and mechanical removal of inflammatory mediators are already being considered or implemented in clinical practice for patients with severe covid-19. thus, as the covid-19 pandemic spreads worldwide, icu practitioners are facing a surge in critically ill patients who need acute and critical modalities. 3. extracorporeal blood purification (ebp) for patients with severe covid-19 ebp therapies are proposed as promising adjunctive treatments, designed for elimination of toxins and removal of inflammatory mediators. even though a growing body of evidence indicates the beneficial impact of ebp use, at this stage, there are controversial reports on these techniques that should be explored (21). historically, ebp modalities have been recommended as complementary treatment methods for a serious overdose from a number of toxins, including salicylates, lithium, ethylene glycol, methanol, and theophylline (22-24). however, multiple extracorporeal devices have been evolved, with the intent to remove endotoxins and modulate the level of inflammatory mediators, such as cytokines/chemokines, the complement system components, and factors involved in coagulation system (21, 25-28). the general mechanism of ebps relies on the removal of various solutes, substances, and excessive fluid from blood through diffusion, convection, or adsorption. in these methods, patients are connected to ebp machines and their blood or plasma is pumped out of a device outside the body, passing through a column containing affinity particles. the comthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e67 mon ebp techniques include hemodialysis, hemofiltration and hemodiafiltration, hemoperfusion, therapeutic plasma exchange, continuous renal replacement therapy, peritoneal dialysis (pd), and albumin dialysis. hemoperfusion therapy was first introduced in the 1940s, using an ionic resin to remove uremic toxins in dogs (29). results from subsequent studies were sufficiently favorable to merit further research and clinical applications (30, 31). the major mechanism of hemoperfusion is elimination of circulating inflammatory mediators and endotoxins, when large volumes of the patient’s blood are passed over its adsorbent substance. circulating endotoxin or inflammatory mediators are attached to the highly adsorptive membrane through hydrophobic, ionic, and van der waals interaction; thus, being eliminated from circulation (25-27). the sorbent system is made up of a biocompatible fixed bed, or cartridge, which contains the adsorbent particles. there are two major types of adsorbent materials, including activated charcoal and resins (e.g. hydrocarbon polymer, polystyrene). charcoal has greater affinity for water-soluble molecules, whereas resins have higher affinity toward lipid-soluble molecules (e.g., glutethimide and methaqualone). particular characteristics of solutes such as molecular size, chemical affinity, and their distribution volume in the body determine the efficacy of the hemoperfusion. over the years, improvement of biocompatibility and adsorption capacity of hemoperfusion systems increased their use in the critical care settings. therefore, even though, classical application of hemoperfusion was elimination of drug or chemical toxics from circulation, recently treatment of inflammatory conditions has been suggested as a potential use for hemoperfusion. regardless of limited evidence, hemoperfusion administration for removal of inflammatory mediators from the bloodstream has been reported to have a beneficial impact on the treatment of dysregulated inflammatory conditions (32). for instance, application of this technique has been reported to have favorable effects in several cases of influenza (especially h1n1 and h5n1 subtypes) (33, 34). moreover, hemoperfusion has successfully been used to immediately ameliorate severe css and prevent mod, pneumonia, and hydrosarca caused by chimeric antigen receptor (car) t cell therapy (35, 36). though not definitive, the profile of cytokine and inflammation in sars-cov 2 infection suggests that a severe dysregulated inflammatory response is a fundamental problem in quite some critically ill covid-19 patients (37-40). therefore, the rationale of using extracorporeal organ support therapies including hemoperfusion, with efficient sorbent cartridges for removal of cytokines and other inflammatory circulating mediators, should be considered in criticallyill covid-19 patients (41). to date, various centers in different countries including italy, china, usa, germany, and iran have reported or are investigating the beneficial effects of different hemoperfusion systems, including ha380/ha330 cartridges, cytosorb, and polymyxin b immobilized fiber column in treatment of critically-ill covid-19 patients. the ha type hemoperfusion cartridges (ha130, ha230, ha330 and ha380) ( jafron, china) are among the widely used ha devices in china. the cartridges contain highly biocompatible sorbents and neutro-macroporous resin made of styrene-divinylbenzene copolymer. ha 330 and ha 380 cartridges are mainly used in acute inflammatory conditions. their adsorbing beads’ pore size ranged from 500 d to 60 kd, giving them the ability to absorb various mediumsized factors, including most inflammatory cytokines (il-1, il-6, il-8, and tnf-a) (42). the results of multiple studies have demonstrated that application of ha 330 to eliminate circulating and alveolar levels of pro-inflammatory cytokines in severe sepsis, septic shock, or acute lung injury patients significantly improved patients’ hemodynamics, reduced the length of intensive care unit stay, and intensive care unit mortality (42-44). currently, a clinical trial is ongoing (irct20200317046797n5, imam reza hospital, tabriz, iran) for evaluating the effectiveness of ha 330 to remove cytokines in patients admitted with severe forms of covid-19 and before intubation. severity of pneumonia based on ct scan, ards, mortality rate, and hospitalization duration are the main variables that will be evaluated in this study. meanwhile, a number of studies, mostly published in europe, have evaluated the clinical use of other hemoperfusion type, cytosorb cartridges (cytosorbents corporation, nj, usa), in the management of conditions associated with elevated inflammatory mediators (45). cytosorb cartridges contain biocompatible highly porous copolymers, capable of binding a broad spectrum of hydrophobic compounds with a molecular weight between 10 and 55 kda. even though most cytokines and other inflammatory mediators reside within this molecular weight range, their removal is concentration dependent. thus, low cytokine plasma concentrations are not removed efficiently, but high cytokine plasma levels are reduced effectively (46, 47). while blood is passed through the absorbent bed, proteins and other hydrophobic molecules less than approximately 60 kda enter the device pores and attach onto the surface of the hydrophobic polymer via nonpolar interactions, hydrogen bonding, and van der waals forces. to date, a large number of experimental and clinical data, mostly from case reports and case series, have introduced cytosorb as an effective rescue therapy for removal of inflammatory cytokines and achievement of hemodynamic stabilization in critically ill patients with septic shock and kidney failure (47-49). the positive results from these studies have led to the consideration of cytosorb application in critically ill covid-19 patients. in italy, the formal recommendation is made by the italy brescia renal covid task force and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem s. safari et al. 4 a publication by the italian society of nephrology and eraedta, to specifically use cytosorb in severe covid-19 patients with stage 3 renal failure on continuous renal replacement therapy (crrt) (50). meanwhile, the emergency use of cytosorb for icu patients with confirmed or imminent respiratory failure has been approved by us food and drug administration (fda), issuing an emergency use authorization (eua) (51, 52). also, the recent national guidelines on adult covid-19 patients from panama recommend cytosorb therapy if patients have either refractory shock, or have severe or refractory respiratory failure requiring high ventilator support or extracorporeal membrane oxygenation (53). the recent handbook of covid-19 prevention and treatment from zhejiang university school of medicine, china, is also recommending blood purification to treat cytokine storm in critical cases of covid-19 infection (54). in addition to several recommendations for cytosorb therapy in covid-19 patients, health canada’s interim order has recently approved the use of the spectral’s toraymyxint m (pmx) hemoperfusion cartridge to treat covid-19 (55), particularly in cases with ards, diffuse alveolar damage or difficulty maintaining oxygenation, in the presence of hypotensive shock. toraymyxin is composed of covalently immobilized polymyxin b (pmx-b) fiber as an absorbent bed. pmx-b is an antibiotic, which is known to bind to endotoxin, selectively. even though the efficacy of pmx-b immobilized fiber columns for direct hemoperfusion in css related conditions is still debated (56-58), they have already shown promising results in treatment of avian flu (h5n1) and swine flu (h1n1), which cause seasonal epidemic and occasional pandemic outbreaks. application of pmx-b to remove endotoxins from influenza patients showed a significant improvement in chest x-ray results and lung function; in addition, it led the patients to earlier weaning from ventilators (59). according to spectral medical inc, a therapeutic company focused on the development of a treatment for septic shock, elevated levels of endotoxin activity, as measured by their fdaapproved endotoxin activity assay (eaa), have been identified in covid-19 patients in japan, italy, and the us (60). since endotoxin is the primary driver of the css, its elimination by the pmx-b cartridge is supposed to reduce circulating levels of cytokines. thus, hemoperfusion with pmx-b is expected to be an effective method to reduce inflammatory mediators by elimination of endotoxins. an ongoing clinical trial (nct04352985) is currently investigating the efficacy of toraymyxin pmx cartridge with a focus on safety of its application for patients with septic shock and covid-19. to sum up, hemoperfusion for solute removal has been used for years. even though, early indication for hemoperfusion was severe intoxication, in recent years these devices have evolved for the purpose of immunomodulation in acute conditions like sepsis. with a multitude of studies and researches indicating that patients with covid-19 experience an immune response dysregulation and css, this blood purification technique is likely to be a feasible treatment modality in the case of severe sars-cov2 infection. however, the real impact of hemoperfusion on the patient’s clinical course has yet to be determined. thus, in future studies, patient selection should be approached with caution and consideration. 4. declarations 4.1. acknowledgements none. 4.2. sources of funding none. 4.3. authors contributions all the authors meet the standard criteria of authorship based on recommendations of the international committee of medical journal editors. authors orcids saeid safari: 0000-0002-5917-633x reza aminnejad: 0000-0003-0439-0440 4.4. conflict of interest none. references 1. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. lancet (london, england). 2020;395(10223):507-13. 2. yang x, yu y, xu j, shu h, xia j, liu h, et al. clinical course and outcomes of critically ill patients with sars-cov2 pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine. 2020;8(5):475-81. 3. anand d, ray s, bhargava s, das s, garg a, taneja s, et al. proinflammatory versus anti-inflammatory response in sepsis patients: looking at the cytokines. critical care. 2014;18(suppl 2):p13-p. 4. barry 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y, kitamura t, kiyomi f, hayakawa m, hoshino k, kawano y, et al. potential survival benefit of polymyxin b hemoperfusion in patients with septic shock: a propensity-matched cohort study. critical care (london, england). 2017;21(1):134. 59. kodama y, takahashi g, kan s, masuda t, ishibe y, akimaru r, et al. use of direct hemoperfusion with polymyxin b-immobilized fiber for the treatment of septic shock complicated with lemierre syndrome caused by fusobacterium necrophorum. case reports in critical care. 2019;2019:5740503. 60. us fda approves an investigational device exemption for spectral medical pmx to treat covid-19 patients suffering from septic shock 2020 [available from: https://www.globenewswire.com/newsrelease/2020/04/14/2015592/0/en/us-fda-approvesan-investigational-device-exemption-for-spectralmedical-pmx-to-treat-covid-19-patients-sufferingfrom-septic-shock.html. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction css in severe covid-19 extracorporeal blood purification (ebp) for patients with severe covid-19 declarations references emergency. 2018; 6 (1): e49 ca s e re p o rt simultaneous occurrence of dysrhythmia and seizure as a diagnostic difficulty; a case report forod salehi1, hamidreza riasi2, hamideh riasi3, arvin mirshahi4∗ 1. cardiovascular diseases research center, department of pediatrics, vali-e-asr hospital, birjand university of medical sciences, birjand, iran. 2. department of neurology, vali-e-asr hospital, birjand university of medical sciences, birjand, iran. 3. vali-easr hospital, birjand university of medical sciences, birjand, iran. 4. student research committee, birjand university of medical sciences, birjand, iran. received: june 2018; accepted: july 2018; published online: 8 august 2018 abstract: torsades de pointes (tdp) is a rare but hazardous ventricular dysrhythmia caused by an increase in the qt interval of the heart rhythm and is categorized into congenital or acquired types. signs and symptoms of tdp include syncope, seizure, ventricular fibrillation, and even sudden death. according to statistics, among these symptoms, syncope and the seizure can be considered as signs that make the tdp diagnosis difficult. here, we present an infant referring to vali-e-asr hospital in birjand with frequent seizures and aspiration pneumonia. she was diagnosed with torsades de pointes and a medium-sized patent ductus arteriosus, and subsequently underwent a patent ductus arteriosus ligation. keywords: torsade de pointes; seizures; ductus arteriosus, patent; infant © copyright (2018) shahid beheshti university of medical sciences cite this article as: salehi f, riasi h, riasi h, mirshahi a. simultaneous occurrence of dysrhythmia and seizure as a diagnostic difficulty; a case report . emergency. 2018; 6 (1): e49. 1. introduction: torsades de pointes (tdp) is polymorphic ventricular tachycardia (vt) that occurs in the setting of a long-qt interval (qt> 440 ms) and is characterized by a waxing and waning qrs amplitude(1). among the factors that can contribute to increased qt interval and tdp incidence in patients are female sex, electrolyte disorders such as hypokalemia, hypomagnesaemia and hypocalcaemia, digitalis consumption, congestive heart failure and heart diseases, excessive or unbalanced consumption of some cardiovascular and non-cardiac drugs, cocaine abuse, as well as genetic problems such as abnormalities in cardiac ion channels such as sodium and potassium channels(2-6). in these patients, certain genetic tests are performed on the patient and his/her family to diagnose the cause of this dysrhythmia. several clinical panels, in addition to electrocardiogram ∗corresponding author: arvin mirshahi; student research committee, birjand university of medical sciences, birjand, iran. email: mirshahiarvin13750@gmail.com tel: 00989394212442 examination, can be found in patients with tdp, which can include heart palpitation, syncope, and seizure (7, 8). in the following case, we study an infant who was referred to vali-e-asr hospital in birjand with frequent seizures and aspirations and was diagnosed with tdp and a medium-sized patent ductus arteriosus (pda) and subsequently underwent a reconstructive surgery. 2. case presentation: the case was a 15-month-old infant girl weighing 10 kg who was referred to vali-e-asr hospital, birjand, iran, as a result of severe respiratory distress and seizure. at the time of visiting the residency hospital, the infant had an apnea and a heart attack, for which a cardiac massage was performed and the patient was referred to birjand city due to an aspiration pneumonia and seizure. physical examination of the height and weight indicated normal development and head circumference. according to the statements of the patient’s companion, the infant had suffered from seizures several times, one of which occurred at the emergency room and was characterized by this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com f. salehi et al. 2 cyanosis in the face and lips. considering the examinations performed in the emergency department showing 50% o2 saturation without oxygen therapy, reduced consciousness in the patient, and the information from history, the patient was diagnosed with seizure and was accordingly transferred to pediatric intensive care unit (picu) with cardiac monitoring. after a few hours of monitoring, the patient suffered repeated vt attacks (fig 1). therefore, medication was infused within 20 minutes, including 500 mg magnesium sulfate and 10 mg lidocaine, and vt was discontinued. furthermore, conduction of a 24-hour holter electrocardiography (ecg) and echocardiography were put on the agenda. contrary to expectations, after taking antiarrhythmic drugs two days after the first arrhythmia and vt, the patient again suffered arrhythmia as repeated pvc followed by vt; therefore, lidocaine and magnesium sulfate were administered. however, even despite the 20-minute infusion of these two drugs, vt did not stop. finally, 50 mg of amiodarone was administered in 30 minutes with a d2 long check before and after the infusion. after a 24-hour holter ecg monitoring, long qt intervals (qt = 490 ms) and vt were observed (fig 2). given the indication of the occurrence of tdp in the patient, treatment with beta-blockers (propranolol) was initiated and all other anti-arrhythmic drugs were discontinued. ultimately, arrhythmia of the patient was completely controlled. furthermore, the patient’s echocardiography showed left atrial enlargement, left ventricular enlargement, left-to-right shunt, and pda with a mean diameter of 4 mm. also, all values were within the normal range in terms of patient-requested tests, including cbc (complete blood count), natrium, potassium, calcium, magnesium, blood urea nitrogen (bun), creatinine, free t4, thyroidstimulating hormone (tsh), and venous blood gas (vbg). given the size of the pda, surgery was subsequently proposed for the infant, and the patient underwent thoracotomy and pda ligation whereby the patient’s pda was closed. propranolol was discontinued and not used over the course of 6-month, one-year, and two-year periodic follow-ups, and the patient was asymptomatic. also, a list of the drugs that contributed to the arrhythmia was given to the patient to avoid consumption. 3. discussion in some heart diseases, loss of consciousness has movements similar to seizures that can be indicated in clinical examinations. it is believed that the appearance of these symptoms, due to the transient cerebral hypoxia in these patients, results from a temporary reduction of the cardiac output (9, 10). according to recent studies, the probability of misdiagfigure 1: electrocardiogram trace of the patient when dysrhythmia occurred (torsade de pointes). figure 2: 24-hour-ecg holter monitoring with long qtc showing polymorphic ventricular tachycardia (torsade de pointes). nosis of seizure for a patient is 20%, and cardiovascular factors including syncope and arrhythmias are often neglected in these cases, indicating the difficulty of differential diagnosis of seizure and tdp in clinical examinations (11-14). therefore, ecg and cardiac monitoring are advisable in people who have had seizures for the first time. also, taking a precise history of the patient, a family history of premature death under 30 years of age, observation and clinical examination, and the use of ecg can be helpful in the differential diagnosis of seizures and seizure-induced cardiovascular diseases(13). moreover, since many drugs are involved in tdp incidence, it is therefore necessary to be mindful of prescribing drugs for individuals with a possibility of misdiagnosis. it is also necessary to check the history of tdp stimulant drugs in this group. in case of unavoidable use of tdp stimulant drugs, it will provide a more accurate assessment if a set of measures are taken, including a baseline assessment and a 12lead ecg, detailed examination at different times of the day, and/or holter monitoring in cases with high possibility of tdp incidence. it will be helpful for the patient to provide a list of precautionary measures and risk factors (including qt interval prolongers) and to prohibit him/her from using similar drugs that can increase the qt interval. moreover, preventing other contributors to increased qt interval such as electrolyte disorders in these patients is very important (5, 15). given the fact that our case was a candidate for pda closure, careful consideration was given to use of medications durthis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com 3 emergency. 2018; 6 (1): e49 ing surgery. the anesthesiologist and the surgical team were provided with information to prevent the use of prolonged qt medications and recurrent vt attacks during surgery. moreover, regarding the results of genetic tests in patients, it should be noted that in 80% of the trials, those having matched clinical features have a confirmed genetic disorder. despite recommendations given to the parents of our case, these tests were not performed on the patient. moreover, if mutations are confirmed in the series of genes examined in this regard, it is necessary to perform these tests on other family members of the patient, who are asymptomatic. should the tests be positive, the family members should take precautions in terms of taking medications and paying more attention to certain signs, such as seizures and syncope (8). 4. conclusion: the incidence of arrhythmias in children is uncommon, and when occurring, they may present with misleading signs. therefore, the familiarity and mental preparedness of general practitioners and pediatricians with these diseases seem necessary in order to prevent fatal consequences with rapid diagnosis and timely treatment. 5. appendix 5.1. acknowledgements we express our gratitude to colleagues in the pediatric ward of vali-e-asr hospital and the patient’s parents who collaborated with us in data collection. 5.2. author’s contribution f.s managed the patient. h.r and h.r followed the patient and wrote the draft. am completed, revised and approved the article. 5.3. conflict of interest authors have no conflict of interest. 5.4. funding none. references 1. al-khatib sm, stevenson wg, ackerman mj, bryant wj, callans dj, curtis ab, et al. 2017 aha/acc/hrs guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart rhythm society. journal of the american college of cardiology. 2017:24390. 2. makkar rr, fromm bs, steinman rt, meissner md, lehmann mh. female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. jama: the journal of the american medical association. 1993;270(21):2590-7. 3. roden dm. drug-induced prolongation of the qt interval. new england journal of medicine. 2004;350(10):1013-22. 4. salehi f, taheri mmh, riasi h, mehrpour o. recurrent syncope following substance abuse; a case report. emergency. 2017;5(1). 5. yap yg, camm j. risk of torsades de pointes with non-cardiac drugs. british medical journal. 2000;320(7243):1158-9. 6. gowda rm, khan ia, wilbur sl, vasavada bc, sacchi tj. torsade de pointes: the clinical considerations. international journal of cardiology. 2004;96(1):1-6. 7. itoh h, crotti l, aiba t, spazzolini c, denjoy i, fressart v, et al. the genetics underlying acquired long qt syndrome: impact for genetic screening. european heart journal. 2016;37(18):1456-64. 8. kliegman r, stanton b, st geme jw, schor nf, behrman re. nelson textbook of pediatrics edition 20 ed: philadelphia, pa : elsevier, [2016]; 2016. 9. lempert t, bauer m, schmidt d. syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. annals of neurology. 1994;36(2):233-7. 10. baratloo a, rouhipour a, forouzanfar m, rahmati f, hashemi b. hypokalemia-induced abnormal movements: case report. trauma monthly. 2013;18(3):141-4. 11. sabu j, regeti k, mallappallil m, kassotis j, islam h, zafar s, et al. convulsive syncope induced by ventricular arrhythmia masquerading as epileptic seizures: case report and literature review. journal of clinical medicine research. 2016;8(8):610. 12. scheepers b, clough p, pickles c. the misdiagnosis of epilepsy: findings of a population study. seizure. 1998;7(5):403-6. 13. smith d, defalla b, chadwick d. the misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic. qjm. 1999;92(1):15-23. 14. angus-leppan h. first seizures in adults. bmj. 2014;348:g2470. 15. isbister gk. risk assessment of drug-induced qt prolongation. australian prescriber. 2015;38(1):20. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: www.jemerg.com introduction: case presentation: discussion conclusion: appendix references emergency (****); * (*): *-* this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com \ emergency (2013); 1 (1): 11-14 11 original research nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial hossein alimohammadi1, majid shojaee1*, mehdi samiei2, somayeh abyari1, ali vafaee1, alireza mirkheshti3 1. department of emergency medicine, imam hossein hospital, shahid beheshti university of medical sciences, tehran, iran 2. department of emergency medicine, hamedan university of medical sciences, hamedan, iran 3. department of anesthesiology, shahid beheshti university of medical sciences, tehran, iran abstract introduction: given the high prevalence of upper extremity fractures and increasing need to perform painless reduction in the emergency departments, the use of analgesic methods with fewer complications and more satisfaction appears to be essential. the aim of this study is comparison the nerve stimulator guided axillary block (nsab) with intravenous sedation in induction of analgesia for painless reduction of distal radius fractures. methods: in the present randomized clinical trial, 60 patients (18-70 years of age) suffered from distal radius fractures, were divided into two equal groups. one group received axillary nerve block by nerve stimulator guidance and the other procedural sedation and analgesia (psa) using midazolam/fentanyl. onset of analgesia, duration of analgesic effect, total procedure time and pain scores were recorded using visual analogue scale (vas) and the outcomes were compared. chi-squared and student t test were performed to evaluate differences between two groups. results: sixty patients were randomly divided into two groups (83.3% male). the mean age of patients was 31 ±0.7 years. while the onset of analgesia was significantly longer in the nsab group, the mean total time of procedure was shorter than psa (p<0.001). the nsab group needed a shorter post-operative observation time (p<0.001). both groups experienced equal pain relief before, during and after procedure (p>0.05). conclusion: it seems that shorter post-operative monitoring time and consequently lesser total time of procedure, make nerve stimulator guided axillary block as an appropriate alternative for procedural sedation and analgesia in painless reduction of distal radius fractures in emergency department. key words: nerve block; nerve stimulator; procedural sedation and analgesia; radius fracture cite this article as: alimohammadi h, shojaee m, samiei m, abyari s, sabzghabaei a, vafaee a. nerve stimulator guided axillary block in painless reduction of distal radius fractures; a randomized clinical trial. emergency. 2013;1(1):11-4. introduction:1 iven the high prevalence of upper extremity fractures and increasing requirement to perform painless reduction in the emergency departments, the use of analgesic methods with fewer complications and more satisfaction appears to be essential (1, 2). procedural sedation and analgesia (psa) is associated with rare but serious complications and need for constant hemodynamic monitoring (3). nowadays, the benefits of regional anesthesia in fracture manipulation have been proven (4). axillary nerve block introduced by halsted and hall in 1884, and has been approved as a safe and effective analgesic method for a variety of upper extremity fractures (5). beside, nerve stimulator guided axillary block (nsab) has recently been used with higher efficacy for this purpose (6, 7). some of ad *corresponding author: majid shojaee; department of emergency medicine, imam hossein hospital, shahid madani avenue, tehran, iran. tel/fax +982177558081; email: m.shojaee@sbmu.ac.ir received: 1 october 2013; accepted: 17 november 2013 vantages of this technique are better localization of the nerve and consequently a shorter time needed for completing the block procedure, lower use volume of the local anesthetic agent, lower incidence of toxicity with local anesthetic agents, faster initiation and more profound block, fewer complications, lower cost and higher patient satisfaction (7-9). according to the above mentioned, the aim of this study is to compare the nsab with psa to induction of analgesia for painless reduction of distal radius fractures. methods: study design and setting this randomized clinical trial compares nsab and psa in induction of analgesia for painless reduction of distal radius fractures. the protocol of the study was prepared based on helsinki declaration and approved by the ethics committee of shahid beheshti university of medical sciences (code: 6451). for ethical reasons, there was no placebo arm. before any procedure, written informed consent was obtained and the procedural steps and the complications and advantages of each technique were explained. g mailto:m.shojaee@sbmu.ac.ir this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com alimohammadi et al 12 participants the subjects of the present clinical trial were selected from the patients suffering from distal radius fracture (age range: 18-70 years) and referred to the emergency department of imam hossein hospital, tehran, iran in march 2011 to march 2012. the random number table was used to assign patients to nsab or psa groups. patients with the following criteria were excluded from the study: severe trauma to other body organs, dislocations, cerebral or visceral hemorrhage, pulmonary trauma; cardiac and pulmonary diseases, chronic use of any medications; drug or alcohol abuse, any neuropathy or history of neuropathy, and patients not willing to take part in the study. intervention after a definite diagnosis of distal radius fracture (based on radiography and confirmation of the need for reduction by orthopedic consultation), patients were randomly assigned to nsab and psa groups. they received instructions how to present their pain severity using visual analog scale (vas) (10) before, during and after reduction. neurovascular examination was performed in nsab group before and after the procedure. the nerve block was carried out by a trained emergency physician, using 1% lidocaine under sterile condition. the arm was abducted up to a right angle (90°) from the trunk, the elbow was supinated and flexed up to 90°, and the dorsum of the hand was placed on a cushion. after palpation of the axillary artery, the 35mm needle of the nerve stimulator was passed through it under local anesthesia. a total of 5-8 ml (maximum of 4 mg/kg) of 1% lidocaine was injected at the sites of median, radial, and ulnar nerves under the guidance of nerve stimulator at the frequency of 2 hz, a current of 3 ma for 0.1 second, which gradually decreased until it reached 0.5 ma and produced an appropriate nerve response. when adequate analgesia achieved, reduction carried out. in the psa group, midazolam and fentanyl were used for intravenous sedation. midazolam was used at an approximate dose of 0.05-0.1 mg/kg (body weight reported by the patient) and fentanyl at a dose of 1-3 µg/kg. the procedures were carried out under cardiac monitoring, pulse oximetry, and all the necessary equipment to keep the airway open. after intravenous sedation and facture reduction, the patients were monitored until full recovery. discharge criteria was consisted of the following: patency of airways, returning to the baseline level of consciousness, the patient’s ability to sit and talk, stable cardiovascular function, and full implementation of gave orders. outcome basic characteristic of patients, pain score before, during and after reduction, total procedure time, onset of analgesia, and duration of analgesic effect were collected for each patients. total procedure time was defined as duration of time from the initiation of the analgesic procedure to the patients’ full recovery (when the patient status is suitable for sending to take control radiography). onset of analgesia was the period from beginning of analgesic procedure to adequate analgesia. in addition, duration of analgesic effect was defined as duration of time from the initiation to end of analgesia. statistical analysis statistical analysis was carried out using spss version 20.0. student t and chi-squared test were performed for quantities and qualitative variables, respectively. a probability level of < 0.05 was taken to indicate statistical significance. results: sixty patients were randomly divided into two groups of 30 (83.3% male). the mean ages and weight of patients were 31 ±0.7 years and 66.5±5 kg respectively. table 1 compares the basic characteristic of patients between two groups. table 2 compares pain scores of psa and nsab groups before, during and after procedure. the means of total times of procedures in the psa and nsab groups were 29±4 and 26±3 minutes, respectively (p<0.001). the onset of analgesia was significantly shorter in the psa group; 8±1 versus 15±2 minutes in nsab (p<0.001). the mean duration of analgesic effect for psa and block group were 22±4 and 11±2 minutes, respectively (p<0.001). the mean arterial blood pressure and pulse rates after the procedure in the psa and nsab were the same and no patients in each groups show significant change in vital sign during analgesic procedure (p>0.05). none of the subjects exhibited any cardio-vascular, respiratory, and gastro-intestinal complications. in addition, in the nerve block group, no cases of convulsions, and drug reaction were observed. discussion: based on the results of present study, while the onset of analgesia was significantly longer in the nsab group, the mean total time of procedure was shorter (p<0.001). it might be because of a longer period of full recovery in psa group (p<0.001). none of the patients exhibited cardiac, vascular, neurologic and respiratory complications as well as drug reaction. considering the crowdedness of emergency departments and limited facilities, nsab can be helpful in efficient use of resources by decreasing the need for close monitoring during and after induction of analgesia. the technique is relatively easy to use and has a favorable safety. it may significantly reduce the need for deep sedation and systemic opiate analgesia in patients with fractures. cramer et al depicted a success rate of 95% with this technique in forearm fracture reduction (11). also, wedel et al showed a 92.4% success rate of nsab this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com 13 emergency (2013); 1 (1): 11-14 (12). they observed that the occurrence of emesis and the use of narcotics were reduced by nsab than general anesthesia. kriwanek et al reported that nsab is an effective option for upper extremity procedure during reduction of forearm fractures (13). stone et al by performing two study stated that ultrasound-guided supraclavicular brachial plexus nerve blocks reduce emergency department length of stay compared with procedural sedation for the treatment of upper extremity fractures, dislocations, or abscesses (3, 14). numerous complications have been pronounced after nsab, including hematoma, systemic toxicity, transient dysesthesias, infection, and temporary neuralgia (15, 16), none of which occurred in present study. application of a smaller needle, proper patient selection, and exercising extra care to avoid intra-arterial injection by frequent aspiration during administration minimized the risks of this procedure. the small number of patients is one of the most important limitation of present study because it may lead to underestimation of complication in both groups. in addition, convenience-sample strategy used in this study decreases enrollment of eligible subjects and may increase potential enrollment bias. however, the authors believe that this issue did not against the findings because randomization guaranteed that the two groups were similar with respect to demographic characteristics and fracture types. finally, due to performing the study in a busy urban emergency department, generalization of it is impossible. it is unknown whether an nsab would result in considerably reduce mean total procedure time in other settings or not. conclusion: it seems that shorter post-operative monitoring time and consequently lesser total time of procedure make nerve stimulator guided axillary block as an appropriate alternative for procedural sedation and analgesia in painless reduction of distal radius fractures in emergency department. acknowledgments: we thank the emergency department staff of imam hossein hospital for helping us in conducting this study. conflict of interest: none funding support: none author’s contributions: all authors passed four criteria for authorship contribution based on recommendations of international committee of medical journal editors. references: 1. grant cr, checketts mr. analgesia for primary hip and knee arthroplasty: the role of regional anaesthesia. crit care pain. 2008;8(2):56-61. 2. ootes d, lambers kt, ring dc. the epidemiology of upper extremity injuries presenting to the emergency department in the united states. hand. 2012;7(1):18-22. 3. stone mb, wang r, price dd. ultrasound-guided supraclavicular brachial plexus nerve block vs procedural sedation for the treatment of upper extremity emergencies. am j emerg med. 2008;26(6):706-10. 4. alimohammadi h, azizi m-r, afshin a, safari s, kariman h, hatamabadi h. axillary nerve block in comparison with intravenous midazolam/fentanyl for painless reduction of upper extremity fractures. acta med iran. 2013;[in press]. 5. olch pd. william s. halsted and local anesthesia: contributions and complications. anesthesiology. 1975;42(4):479-86. 6. sia s, lepri a, marchi m. axillary block by "selective" injections at the nerves involved in surgery using a peripheral nerve stimulator: a comparison with a "standard" tripleinjection technique. reg anesth pain med. 2010;35(1):22-7. 7. turkan h, baykal b, özisik t. axillary brachial plexus blockade: an evaluation of three techniques. mil med. 2002;167(9):723-5. 8. rothe c, asghar s, andersen h, christensen j, lange k. ultrasound-guided block of the axillary nerve: a volunteer study of a new method. acta anaesthesiol scand. 2011;55(5):565-70. 9. lee sm, park s-e, nam y-s, et al. analgesic effectiveness of nerve block in shoulder arthroscopy: comparison between interscalene, suprascapular and axillary nerve blocks. knee surg sports traumatol arthrosc. 2012;20(12):2573-8. 10. todd kh, funk kg, funk jp, bonacci r. clinical significance of reported changes in pain severity. ann emerg med. 1996;27(4):485-9. 11. cramer ke, glasson s, mencio g, green ne. reduction of forearm fractures in children using axillary block anesthesia. j orthop trauma. 1995;9(5):407-10. 12. wedel dj, krohn js, hall ja, editors. brachial plexus anesthesia in pediatric patients. mayo clin proc; 1991: table 1: basic characteristic of patients  variables nsab3 psa4 p age (year) 31±10 31±6 0.707 weight (kg) 67±6 66±6 0.263 gender (%) female 3 (10) 7 (23.3) 0.166 male 27 (90) 23 (76.7) map1(mmhg) 99±8 98±7 0.27 pr2(per minute) 77±6 72±7 0.32 1: mean arterial blood pressure, 2: pulse rate, 3: nerve stimulator guided axillary nerve block, 4: procedural sedation and analgesia table 2: comparison of pain severity before, during and after reduction of fractures based on visual analogue scale (mean ± standard deviation)  pain severity nsab1 psa2 p before reduction 9±1 10±1 0.90 during reduction 1±1 1±1 0.85 after reduction 1±0 1±0 0.16 1: nerve stimulator guided axillary nerve block, 2: procedural sedation and analgesia this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). copyright © 2013 shahid beheshti university of medical sciences. all rights reserved. downloaded from: www.jemerg.com alimohammadi et al 14 elsevier. 13. kriwanek kl, wan j, beaty jh, pershad j. axillary block for analgesia during manipulation of forearm fractures in the pediatric emergency department a prospective randomized comparative trial. j pediatr orthoped. 2006;26(6):737-40. 14. stone mb, price dd, wang r. ultrasound-guided supraclavicular block for the treatment of upper extremity fractures, dislocations. am j emerg med. 2007;25(4):472-5. 15. stan tc, krantz ma, solomon dl, poulos jg, chaouki k. the incidence of neurovascular complications following axillary brachial plexus block using a transarterial approach: a prospective study of 1,000 consecutive patients. reg anesth pain med. 1995;20(6):486-92. 16. ben-david b, stahl s. axillary block complicated by hematoma and radial nerve injury. reg anesth pain med. 1999;24(3):264-6. archives of academic emergency medicine. 2020; 8(1): e88 ca s e re p o rt pulmonary thromboembolism and infarction mimicking covid-19 symptoms; report of three cases rama bozorgmehr1, mehdi pishgahi2, zohreh tajabadi 3∗, mohammad aryafar4 1. clinical research development unit, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 2. cardiology research center, shohadaye tajrish hospital, shahid beheshti university of medical sciences, tehran, iran. 3. student research committee, school of medicine, shahid beheshti university of medical sciences, tehran, iran. 4. department of anesthesiology, tehran medical sciences branch, islamic azad university, tehran, iran. received: october 2020; accepted: october 2020; published online: 2 november 2020 abstract: since the novel coronavirus emerged in late december, 2019 in wuhan, china, millions of people have been infected and thousands of patients have died. fever and dyspnea are the most common symptoms of infection with sars-cov-2. however, these symptoms are neither specific nor diagnostic for covid-19. symptom overlap between covid-19 and some other conditions may lead other diseases to be missed and underdiagnosed. just like covid-19, pulmonary thromboembolism (pte) and pulmonary infarction may present with fever and respiratory symptoms. since covid-19 emerged and spread worldwide, many clinicians are focused on diagnosis and treatment of this novel viral infection. hence, other diseases presenting with the same symptoms as covid19 may remain underdiagnosed. here, we report three cases of pte and pulmonary infarction presenting with fever and respiratory symptoms mimicking covid-19. keywords: pulmonary embolism; pulmonary infarction; covid-19; venous thrombosis; signs and symptoms, respiratory cite this article as: bozorgmehr r, pishgahi m, tajabadi z, aryafar m. pulmonary thromboembolism and infarction mimicking covid-19 symptoms; report of three cases. arch acad emerg med. 2020; 8(1): e88. 1. introduction sars-cov-2 is a single-strand rna virus, which belongs to coronaviridae family (1). since the novel coronavirus emerged in late december, 2019 in wuhan, china, millions of people have been infected and thousands of patients have died. nowadays, covid-19 pandemic is a major concern for both people and health-care systems. fever and dyspnea are the most common symptoms of infection with sarscov-2 (2). however, these symptoms are neither specific nor diagnostic for covid-19. many other diseases initially present with fever and respiratory symptoms. symptom overlap between covid-19 and some other conditions may result in other diseases being missed and underdiagnosed. underdiagnosis of the disease may increase the risk of morbidity and mortality due to misdiagnosis, mistreatment, or delay in treatment initiation. like covid-19, pulmonary ∗corresponding author: zohreh tajabadi, shahid beheshti university of medical sciences, faculty of medicine, evin, tehran, iran. tel: +989399304075, email: zohre.tajabadi@sbmu.ac.ir. orcid: https://orcid.org/0000-0002-98547260 thromboembolism (pte) may present with fever and respiratory symptoms such as dyspnea, tachypnea and hemoptysis (1). pte occurs among one third of patients with deep vein thrombosis (dvt) and is associated with increased risk of morbidity and mortality (3). furthermore, recent researches have demonstrated that covid-19 is associated with coagulopathy and increases the risk of dvt and pte (4). due to overlap of symptoms and findings between these conditions, diagnosis of these diseases is challenging. during covid19 pandemic, pulmonary thromboembolism, pulmonary infarction, and other diseases presenting with fever and respiratory symptoms should also be considered to prevent misdiagnosis of these diseases. in this series, pulmonary thromboembolism and associated pulmonary infarction mimicking the symptoms and findings of covid-19 is reported in a young post-partum woman with history of thrombosis, an old woman with a history of recent trauma, and a young man without any history of underlying medical diseases. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 2 figure 1: central filling defect in right inter-lobar artery and left lower segmental artery with infarction of both peripheral superior segments of right lower lobe and left lower lobe. 2. case presentations 2.1. case 1 a 29-year-old postpartum woman from qom city, where the first covid-19 case in iran was observed, presented to our emergency department with a history of dyspnea, tachypnea, and pleuritic chest pain. at the time of admission, an o2 saturation of 92%, heart rate of 108 bpm, respiratory rate of 28/minutes and oral temperature of 38 0c were noted. her blood pressure was within the normal range. physical examination revealed edema, tenderness, and warmth of the right leg. the left leg was normal in physical examination. electrocardiogram was normal. at the time of admission, laboratory tests revealed normal white blood cell count (6.2×103/mm3), platelet count (226×103/mm3), blood urea nitrogen (14 mg/dl) and creatinine (0.8 mg/dl). in blood examination, hemoglobin =10.1 gr/dl, prothrombin time=16 seconds, international normalized ratio (inr) =1.4, and erythrocyte sedimentation rate (esr) = 50 mm/hour were noted. liver function tests were normal. other laboratory parameters were in normal ranges. due to dyspnea and fever, spiral chest computed tomography (ct) scan was done to assess covid-19, which had some bilateral and sub-pleural patchy ground glass infiltration. the radiologist report was consistent with covid-19. but the patient had a history of left leg pain and edema from seven days ago and because of that we considered pulmonary thromboembolism and pulmonary infarction. the patient had a previous history of left transverse and sigmoid sinus thrombosis, right cavernous sinus thrombosis, and several episodes of seizure six years ago. the patient was on heparin treatment for six years but had received no treatment during pregnancy. since the symptoms and ct scan findings were consistent with both covid19 and pulmonary infarction, the reverse transcriptase polymerase chain reaction (rt-pcr) test and a multi-detector ct angiography of lungs were performed. the rt-pcr test showed negative results. ct angiography demonstrated evidences of central filling defect in left lower artery and right inter-lobar artery extending to segmental branches (figure 1). furthermore, bilateral wedge-shaped consolidation of peripheral superior segment was found. findings of ct angiography were consistent with pulmonary thromboembolism (pte) and pulmonary infarction. she also underwent color-flow doppler sonography, which indicated abnormal venous flow in right common femoral, superficial femoral, popliteal, and external iliac veins indicating acute deep vein thrombosis (dvt) in these veins. during compression ultrasound, the veins were unable to compress. venous blood flow was normal through inferior vena cava. echocardiography showed normal ventricular size and function. no evidence of pulmonary thromboembolism was detected on echocardiography. therefore, due to previous history of thrombophilia and concurrent dvt, pulmonary thromboembolism leading to pulmonary infarction was diagnosed and anticoagulant therapy was started. several days after admission, she developed fever and chills, and dyspnea worsened. due to a high suspicion of covid-19, both rt-pcr test and igm and igg antibody tests for covid-19 were performed, which showed negative results and covid-19 was ruled out. since postpartum women are at increased risk of infections and also pulmonary infarction is associated with a greater risk of infections, pneumonia was considered in this patient. therefore, intravenous antibiotic therapy was initiated. subsequently, sputum smear and culture for bacterial infections were performed, which showed negative results. furthermore, all thrombophilic evaluations were negative. during hospitalization, leg pain and edema improved gradually. fever and chills resolved. patient’s clinical condition significantly improved and she was finally discharged from the hospital. 2.2. case 2 an 80-year-old woman from tehran presented to our emergency department with a history of one week of dyspnea, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2020; 8(1): e88 figure 2: filling defect in left main pulmonary artery and right lower lobe with bilateral sub-pleural infarction. productive cough, and left-sided pleuritic chest pain. the patient had a history of asthma and was receiving salbutamol. she had a history of falling down resulting in a blunt chest trauma about three weeks ago. at the time of admission, an o2 saturation of 93% and a respiratory rate of 24/minutes was noted. heart rate, blood pressure, and oral temperature were within normal ranges. on physical examination, inspiratory basal crackles in left lung were noted. the right lung was clear on auscultation. an electrocardiography was performed, which was normal. at the time of admission, laboratory tests revealed normal white blood cell count (5.9×103/mm3), platelet count (314×103/mm3), esr (6 mm/hour), c-reactive protein (crp) (5.6 mg/dl), and creatinine (1.32 mg/dl). in blood examination, blood urea nitrogen = 30 mg/dl, hemoglobin = 11.3 gr/dl, calcium = 11.15 mg/dl, and phosphorus = 5.5 mg/dl were noted. venous blood gas analysis was normal for ph (7.39), pco2 (40 mmhg) and hco3 (23.9 meq/l). other laboratory parameters were within normal ranges. due to respiratory symptoms, a spiral chest ct scan was performed on admission, which showed ground glass opacities of sub-pleural regions in left lung. ct imaging revealed multiple consolidations and atelectasis in right lung. the radiologist report was consistent with covid-19. however, since symptoms and imaging findings were consistent with both covid-19 and pulmonary infarction, the patient underwent rt-pcr test and ct angiography. the rt-pcr test revealed negative results. ct angiography of lungs showed evidence of filling defect in left pulmonary artery extending to segmental branches, which was consistent with pulmonary infarction due to pulmonary embolism (figure 2). ct angiography revealed no abnormal findings in right lung. subsequently, the patient underwent color-flow doppler sonography of lower extremities to find evidence of any vein thrombosis. however, no findings of acute dvt were reported. since the diagnosis of pte and pulmonary infarction was confirmed, anticoagulant therapy was started. during hospitalization, the levels of hemoglobin gradually decreased to 10.7 gr/dl, and esr and crp increased to 24 and 33.2 mg/dl, respectively. during hospitalization, dyspnea and pleuritic chest pain improved and productive cough was resolved gradually. after six days, the patient was discharged without any complaints or complications. 2.3. case 3 a 23-year-old man presented to our emergency department with a history of progressive dyspnea and dry cough from 10 days ago. he also complained of right-sided chest pain that exacerbated by lying flat, which had started 3 days ago. fever and sore throat also started one day ago. he had a history of exposure to covid-positive patients during the last two weeks. the patient denied any history of underlying medical diseases. he also denied any history of smoking, alcohol, or drug use. at the time of admission, a heart rate of 125 beat/minute and blood pressure of 100/75 mmhg were noted. o2 saturation was 91% in room air, which increased to 97% with mask. respiratory rate and oral temperature were normal. physical examinations did not reveal any abnormalities. the heart and lungs were clear to auscultation. on admission, blood examinations revealed white blood cell count (wbc) =7500×103 /mm3; hemoglobin =14.9 gr/dl; platelet = 196000; crp=10 mg/dl and esr = 7 mm/hour, all of which were within normal ranges. biochemical tests showed creatinine = 0.9 mg/dl; blood urea nitrogen (bun) = 13 mg/dl; na = 140 meq/l; k = 3.5 meq/l; creatine phosphokinase (cpk) = 162 iu/l; creatine kinase-mb (ckmb) = 21 iu/l, and lactate dehydrogenase (ldh) = 381 u/l. venous blood gas analysis demonstrated a ph of 7.35, pco2 of 51.9 mmhg, and hco3 of 27.9 meq/l, which were indicative of respiratory acidosis. due to fever, respiratory symptoms, and recent history of exposure to covid-positive patients, initially, covid19 was suspected. the patient underwent spiral ct scan of lungs, which revealed bilateral and sub-pleural ground glass opacities. since symptoms and imaging findings were consistent with both covid-19 and pulmonary infarction, the patient underwent rt-pcr test and ct angiography. the result of rt-pcr test for covid-19 was negative. ct angiography of lungs showed massive pte in both right and this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 4 figure 3: central filling defect in main pulmonary branch of left lower lobe with infarction in posterior-basal segment of left lower lobe on pulmonary angiography. left pulmonary arteries (figure 3). furthermore, peripheral patchy lesions without enhancement were seen, which were indicative of pulmonary infarction in both lungs. therefore, infection with sars-cov-2 was ruled out and the diagnosis of pulmonary infarction due to pte was confirmed for the patient by performing echocardiography and colorflow doppler sonography of the abdomen and lower limbs. echocardiography revealed a large pte and a severely dilated right ventricle. however, color-flow doppler sonography showed no evidence of acute dvt. furthermore, mesenteric veins had normal blood flow and peak systolic velocity. since the diagnosis of pte and pulmonary infarction was confirmed using imaging, fibrinolytic and anticoagulant therapy were started. prothrombine time (pt), partial thromboplastin time (ptt), and inr were closely monitored. during hospitalization, dyspnea, productive cough, and chest pain resolved. the fever improved gradually. on the last day of hospitalization, blood tests revealed wbc=5100/mm3; hemoglobin = 14.9 gr/dl; platelet count = 233000/mm3; pt = 13 seconds; inr = 1 and ptt = 32 seconds, which were all within normal ranges. the patient was discharged on the sixth day without any complications. 3. discussion covid-19 emerged in winter, 2019 in wuhan province, china and rapidly spread all over the world. in march 2020, world health organization declared covid-19 as a pandemic (5). to date more than 20,000,000 people have been infected around the world. infection with this novel coronavirus is associated with a considerable rate of morbidity and mortality. covid19 usually presents with fever and respiratory symptoms including dyspnea, tachypnea, cough, and hemoptysis. these symptoms are neither specific nor diagnostic for covid-19. many other infectious or respiratory disorders also present with constitutional and respiratory symptoms. hence, during covid-19 pandemic, for the patients presenting with fever and respiratory symptoms, other diseases should also be considered to prevent misdiagnosis of the underlying disease. pulmonary thromboembolism and pulmonary infarction are among the respiratory disease, which usually present with respiratory symptoms such as dyspnea, chest pain, and hemoptysis. recent researches have indicated that covid19 increases the risk of thrombosis development. a recent study carried out by pishgahi et al., reported massive thromboembolism development among three icu admitted patients with covid-19 (6). patients with covid-19 usually suffer from hypoxia and sepsis, which are among the major causes of thrombosis formation (4). furthermore, the novel coronavirus can infect cells via ace2 receptor, which results in endothelial damage (6). however, the exact mechanism is unknown. covid-19 can induce inflammation, platelet activation, endothelial dysfunction, and stasis, leading to thrombotic events such as dvt and pte (7). thrombotic events are associated with increased risk of death among patients infected with sars-cov-2 virus (4). deep vein thrombosis accounts for two-thirds of venous thromboembolism cases, occurring in 1 out of 1000 individuals each year (3). venous stasis, vascular injury, and hypercoagulability, known as “virchow’s triad”, are the major factors leading to thrombosis formation (3). pregnancy, prolonged immobility, and previous history of thrombosis are associated with an increased risk of dvt. our first patient had the history of recent pregnancy, previous hypercoagulability, and cerebral vein thrombosis associated with increased risk of thrombotic events. patients with dvt usually present with leg pain, warmth sensation, swelling and leg ulcers (3). also patients with dvt may be asymptomatic (7). because of safety, cost-effectiveness, and reliability, ultrasound imaging is the first modality used for the diagnosis of dvt (3). color-flow doppler sonography this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2020; 8(1): e88 is also used for better evaluation of thrombosis. the reported patients underwent color-flow doppler sonography. the first patient had no normal venous flow in right common femoral, superficial femoral, popliteal, and external iliac veins, indicating acute dvt in these veins. these findings were consistent with dvt. however, other patients showed no evidence of vein thrombosis in color-flow doppler sonography. sometimes dvt may progress to pte. pte is among the major manifestations of venous thromboembolism. pulmonary thromboembolism can present with a wide range of nonspecific symptoms, which makes the diagnosis of the disease difficult (8). studies showed that patients with covid-19 are at an increased risk of pte development. ohana et al., reported that 30% of patients with covid-19 developed pte, which was greater than pte rate among ill patients without sars-cov-2 infection (9). pte can lead to pulmonary infarction, which is a rare complication of pulmonary embolism (10). pulmonary infarction does not occur frequently due to robust oxygenation supports and vascular supplies of lungs from pulmonary circulation, bronchial circulation, and airways (11). risk factors for pulmonary infarction are the same as dvt and pte (12). pulmonary infarction may present with chest pain, bleeding, and hemoptysis. however, pleuritic chest pain and sudden dyspnea are the most common symptoms of pulmonary infarction (11). these three patients all presented with dyspnea and chest pain. a retrospective study carried out by chengsupanimit et al., reported that sixmonth survival of patients who develop pulmonary infarction was 88%. also researchers found that 55% of patients with pulmonary infarction had a history of dvt (10). concurrent peripheral consolidation and central clearance, mixed peripheral consolidation with ground glass opacity (ggo), and peripheral ggo are among the most common ct scan findings in patients who develop pulmonary infarction (10). on the other hand, ggo, mixed ggo, crazy-paving patterns, peripheral and subpleural consolidations, and bilateral involvement of both lower lungs are among the typical findings of ct scan among patients with covid-19 (13). therefore, in the presence of these findings, both covid-19 and pulmonary infarction should be considered. the reported patients underwent ct scan of lungs, which revealed multiple consolidations and ground glass opacities. ct scan findings were consistent with both covid-19 and pulmonary infarction. covid-19 was considered first. however, reverse transcriptase polymerase chain reaction for covid-19 showed negative results and other diseases were considered. during covid-19 pandemic, some of the diseases may remain underdiagnosed. covid-19 usually presents with constitutional symptoms such as fever, chills, myalgia, fatigue, and respiratory symptoms including dyspnea, cough, and tachypnea, and in some cases hemoptysis. many other clinical situations such as malignancies, anemia, metabolic disorders, and infections may also initiate with constitutional symptoms. furthermore, respiratory disorders such as upper respiratory tract infections, pneumonias, pulmonary embolism, and pulmonary infarction can present with respiratory symptoms. since covid-19 emerged and spread worldwide, many clinicians are focused on diagnosis and treatment of this novel viral infection. hence, other diseases presenting with the same symptoms as covid-19 may remain underdiagnosed. in the reported cases, pte and pulmonary infarction presented with fever and respiratory symptoms, mimicking covid-19. since there was high suspicion for covid-19, diagnostic tests were performed, which showed negative results. after covid-19 was ruled out, the diagnosis of underlying pulmonary condition was considered. ct angiography of lung confirmed the diagnosis of pte associated with pulmonary infarction. when the diagnosis of pulmonary infarction due to pte was confirmed, anticoagulant therapy was started. studies showed that anticoagulant therapy decreases the risk of thrombosis recurrence (3). also, recent researches demonstrated that thromboprophylaxis and anticoagulant therapy lower the risk of mortality among patients with severe covid-19 (4). during hospitalization, patients’ clinical conditions improved significantly. at the time of writing this manuscript, these patients are still symptomfree. 4. conclusion since covid-19 emerged and spread worldwide, many health-care workers have focused on diagnosis and treatment of this viral infection. similarities between symptoms of covid-19 and many other diseases makes the diagnosis of the underlying disease harder during covid-19 pandemic. under-diagnosis of the diseases leads to delay in diagnosis and treatment initiation, which may increase the risk of patient morbidity and mortality. therefore, it is important to consider other underlying diseases presenting with constitutional and respiratory symptoms during covid-19 pandemic. 5. declarations 5.1. acknowledgements none. 5.2. authors contribution all authors met the criteria for gaining authorship based on the recommendations of the international committee of medical journal editors. 5.3. conflict of interest the authors have no conflicts of interest. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem r. bozorgmehr et al. 6 5.4. funding none. references 1. zuckier ls, moadel rm, haramati lb, freeman lm. diagnostic evaluation of pulmonary embolism during the covid-19 pandemic. journal of nuclear medicine. 2020;61(5):630-1. 2. huang c, wang y, li x, ren l, zhao j, hu y, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet. 2020;395(10223):497-506. 3. stone j, hangge p, albadawi h, wallace a, shamoun f, knuttien mg, et al. deep vein thrombosis: pathogenesis, diagnosis, and medical management. cardiovascular diagnosis and therapy. 2017;7(suppl 3):s276. 4. poggiali e, bastoni d, ioannilli e, vercelli a, magnacavallo a. deep vein thrombosis and pulmonary embolism: two complications of covid-19 pneumonia? european journal of case reports in internal medicine. 2020;7(5). 5. mak s, mak d, hodson d, preston r, retter a, camporota l, et al. pulmonary infarction without pulmonary arterial thrombus in covid-19 patients receiving extracorporeal membrane oxygenation: a case series. clinical radiology. 2020. 6. pishgahi m, aval za, hajimoradi b, bozorgmehr r, safari s, yousefifard m. massive pulmonary thromboembolism in patients with covid-19; report of three cases. archives of academic emergency medicine. 2020;8(1):58. 7. demelo-rodríguez p, cervilla-muñoz e, ordieres-ortega l, parra-virto a, toledano-macías m, toledo-samaniego n, et al. incidence of asymptomatic deep vein thrombosis in patients with covid-19 pneumonia and elevated d-dimer levels. thrombosis research. 2020. 8. bozorgmehr r, pishgahi m, mohaghegh p, bayat m, khodadadi p, ghafori a. relationship between thrombosis risk factors, clinical symptoms, and laboratory findings with pulmonary embolism diagnosis; a cross-sectional study. archives of academic emergency medicine. 2019;7(1). 9. leonard-lorant i, delabranche x, severac f, helms j, pauzet c, collange o, et al. acute pulmonary embolism in covid-19 patients on ct angiography and relationship to d-dimer levels. radiology. 2020:201561. 10. chengsupanimit t, sundaram b, lau wb, keith sw, kane gc. clinical characteristics of patients with pulmonary infarction–a retrospective review. respiratory medicine. 2018;139:13-8. 11. miniati m, editor pulmonary infarction: an often unrecognized clinical entity. seminars in thrombosis and hemostasis; 2016: thieme medical publishers. 12. fosmire st, gibson gn, copeland jc, maydew ms, eggers c. pulmonary infarction: right upper quadrant pain as a presenting symptom with review of typical computed tomography imaging features. military medicine. 2018;183(11-12):e779-e82. 13. kanne jp. chest ct findings in 2019 novel coronavirus (2019-ncov ) infections from wuhan, china: key points for the radiologist. radiological society of north america; 2020. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction case presentations discussion conclusion declarations references archives of academic emergency medicine. 2021; 9(1): e6 https://doi.org/10.22037/aaem.v9i1.875 or i g i n a l re s e a rc h topical tranexamic acid versus phenylephrine-lidocaine for the treatment of anterior epistaxis in patients taking aspirin or clopidogrel; a randomized clinical trial keyvan amini1, amirahmad arabzadeh2∗, sevda jahed3, payman amini3 1. department of emergency medicine, school of medicine, ardabil university of medical sciences, ardabil, iran. 2. department of surgery, school of medicine, ardabil university of medical sciences, ardabil, iran. 3. school of medicine, ardabil university of medical sciences, ardabil, iran. received: september 2020; accepted: october 2020; published online: 19 november 2020 abstract: introduction: epistaxis is one of the most prevalent complaints in the emergency department (ed), especially in patients who take antiplatelet agents. this study aimed to compare the effect of topical use of tranexamic acid (txa) with phenylephrine-lidocaine anterior nasal packing (panp) in controlling epistaxis of patients who take aspirin or clopidogrel. methods: this prospective, double-blind, parallel-group, randomized clinical trial was conducted to compare the effect of topical use of intravenous (iv ) txa compared with panp on controlling anterior epistaxis in patients who take aspirin or clopidogrel. results: one hundred patients with the mean age of 59.24 ± 7.75 (45 – 75) years were studied (52% male). two groups were similar in terms of age (p=0.81) and sex (p=0.23) distribution, diabetes mellitus (p=0.54), and hypertension (p = 0.037). the mean time to stop bleeding was 6.70 ± 2.35 minutes in the txa group and 11.50±3.64 minutes in the panp group (p=0.002). bleeding recurrence occurred in 3 (6%) cases of the txa group and 10 (20%) cases of the panp group (p =0.03). time to discharge from ed in the txa group was significantly lower than the panp group (p<0.001). the absolute risk reduction (arr), relative risk reduction, and number needed to harm of treatment with txa for anterior nasal bleeding were 14.00% (95%ci: 1.11 – 26.89), 17.50% (95%ci: 0.60 37.27), and 7.14 (95%ci: 3.71 -90.43), respectively. conclusion: topical txa is an appropriate treatment option in bleeding cessation, and reducing re-bleeding and duration of hospital stay in patients with epistaxis who take antiplatelet agents. keywords: tranexamic acid; phenylephrine, lidocaine drug combination; epistaxis; aspirin; clopidogrel; emergency medical services cite this article as: amini k, arabzadeh a, jahed s, amini p. topical tranexamic acid versus phenylephrine-lidocaine for the treatment of anterior epistaxis in patients taking aspirin or clopidogrel; a randomized clinical trial. arch acad emerg med. 2021; 9(1): e6. 1. introduction epistaxis is described as bleeding from the nostrils, inner part of the nasal cavity, or nasopharynx, and is one of the most common complaints among patients referring to the emergency department (ed) (1). the lifetime prevalence of epistaxis is about 60% and up to 6% will need medical care (2). global estimations show that nosebleed mostly occurs in children under 10 and elderly over 60 years old, which results in the bimodal age distribution (3). about 90% of nosebleeds ∗corresponding author: amirahmad arabzadeh; department of surgery, fatemi hospital, ardabil, iran. email: amir.arabzadeh@arums.ac.ir, amir_medico@yahoo.com fax number: +984533249947, tel: +984533249947, orcid: https://orcid.org/0000-0001-9594-5522. originate from kiesselbach’s plexus in the anterior nasal septum, while the remaining 10% occurs in the posterior nasal septum or the lateral wall of the nasal cavity (4). many local and systemic conditions such as traumas (physical or medication-induced mucosal traumas), decreased nasal mucosa moisture, septal perforations, viral or bacterial rhinosinusitis, neoplasms, coagulation disorders, and some drugs such as anticoagulant or antiplatelet agents may cause epistaxis (3). although epistaxis is typically self-limiting; it can be life-threatening in elderly patients, especially those who have underlying diseases and take antiplatelet medications such as aspirin or clopidogrel (5). various treatment strategies, from compression therapy to nasal packing, are available in ed to control nosebleed (6). some studies suggest using tranexamic acid (txa), an antifibrinolytic agent, in oral, this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. amini et al. 2 intravenous (iv ), or topical forms to control epistaxis; but the clinical evidence of its use is limited, especially in patients who receive antiplatelet aggregation agents (7-9). since using antiplatelet drugs is common in older ages, it is of great importance to appropriately manage this group of patients. this study aimed to compare the effect of topical use of intravenous (iv ) txa with phenylephrine-lidocaine anterior nasal packing (panp) in controlling epistaxis of patients who take aspirin or clopidogrel. 2. methods 2.1. study design and setting this prospective, double-blind, parallel-group, randomized clinical trial was conducted in the ed of the fatemi hospital, affiliated to ardabil university of medical sciences (arums), to compare the effect of topical use of txa (intravenous (iv ) form) with panp, in controlling anterior epistaxis. this study was approved by the ethics committee of arums (ethics code: ir.arums.rec.1398.249) and was registered on the iranian registry of clinical trials (irct) with the number irct20191008045031n1. before beginning the study, patients were assured that they were free to participate or not, they would not be charged any additional fees for participating, and the researchers adhered to ethical principles and their personal information is completely confidential and would not be published anywhere. the written informed consent was obtained from all participants before the study. 2.2. participants all patients who referred to ed with an episode of epistaxis and were under treatment with antiplatelet drugs (aspirin, clopidogrel, or both) were enrolled in this study. patients not willing to participate in the study and those with multiple trauma, hereditary hemorrhagic or platelet disorders, hemophilia, renal dysfunction, or obvious bleeding from other parts of the body were excluded. 2.3. intervention after diagnosis confirmation by an emergency medicine specialist in the ed, eligible patients were randomly allocated to either receive a single topical application of 1-gram txa iv form (tranexip (b: 215)) or panp (nasophrin (lot: 902872)) using block randomization method. the triage nurse who was blinded to the intervention, delivered prepacked sequentially numbered boxes, which were not accessible to other ed staff and contained intervention material, in the procedure room. the txa group received a wad of cotton steeped in the injectable form of txa (500 mg in 5 ml), which was lodged into the bleeding nostril. the panp group received a wad of cotton steeped in phenylephrine (1:100,000) + lidocaine (2%) lodged into the bleeding nostril and remained for 10 minutes. following bleeding cessation, tetracycline ointment-soaked panp was inserted and left in place for 3 days for both groups. to assess intervention outcomes in both groups, a blinded attending emergency medicine specialist confirmed bleeding cessation and in case of persistent bleeding despite initial intervention, an appropriate second-line treatment e.g., cautery was considered. 2.4. outcome the primary outcome was bleeding cessation time defined as the time it took the treatment to stop bleeding. the secondary outcomes were: (a) bleeding recurrence defined as re-bleeding within 72 hours after the initial bleeding episode, (b) the length of hospital stay, and (c) the relationship between bleeding recurrence with sex, hypertension (htn), and diabetes mellitus (dm) in both treatment arms. patient’s demographic information such as age, sex, duration of aspirin or clopidogrel administration and their dosage were recorded in researcher-developed questionnaires that were filled out by the patients. 2.5. randomization the random allocation sequence was generated by our triage nurse, using spss software for windows version 16, which was stratified by the center. all patients who met the inclusion criteria were randomly allocated to either the txa group or the panp group using a random sampling method. sequentially numbered boxes containing intervention medications and materials were previously prepared and our nurse used a random allocation sequence to allocate a treatment to each patient. the boxes were completely identical in appearance, size, and weight and were delivered sequentially to the medical intern. the triage nurse was blinded to the intervention and the contents of the boxes. because of obvious differences in color and smell of the two medications used for our trial, the medical intern who performed the intervention was not blinded to the intervention. however, the attending emergency medicine specialist who evaluated the treatment outcomes and confirmed the bleeding cessation and bleeding recurrence within 72 hours was completely blinded to the intervention. the person who statistically analyzed the data was also blinded to the group assignment. 2.6. statistical analysis based on the data extracted from a previous similar trial, considering the power of 90%, first type error of 0.5%, efficacy in the group p1 = 28.3, and p2 = 66.7%, the sample size was determined as 40 per group using the sample size formula for the intervention. we assigned the sample size of 50 people to each group considering the possibility of sample drop out. all data were analyzed using statistical package for the sothis open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 3 archives of academic emergency medicine. 2021; 9(1): e6 figure 1: patient allocation flowchart. panp: phenylephrine/lidocaine soaked anterior nasal packing; txa: tranexamic acid. cial sciences (spss) version16. descriptive statistical methods (frequency, percentage, mean ± standard deviation [sd]) were used for the presentation of the findings. independent t-test was used to compare the quantitative findings and chisquare test was used to compare the qualitative findings. pvalues of less than 0.05 were considered significant. the absolute risk reduction, relative risk reduction, and number needed to harm (uncontrolled bleeding) of treatment with txa for anterior nasal bleeding were calculated and reported with 95% confidence interval (ci). 3. results 3.1. baseline characteristics of the studied cased one hundred patients with the mean age of 59.24 ± 7.75 (4575) years were studied (52% male). figure 1 shows the allocation flowchart of the study. baseline characteristics of the studied cases were compared between groups in table 1. the two groups were similar in terms of the age (p = 0.81) and sex (p = 0.23) distribution, diabetes mellitus (p = 0.54), hypertension (p= 0.037), and history of bleeding (p = 0.001). this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. amini et al. 4 3.2. treatment outcomes table 2 compares the treatment outcomes between the groups. the mean time to stop bleeding was 6.70 ± 2.35 minutes in the txa group and 11.50 ± 3.64 minutes in the panp group (p=0.002 ). bleeding recurrence occurred in 3 (6%) of the cases who were treated with txa and 10 (20%) cases treated with panp (p=0.03). time to discharge from ed in the txa group was significantly lower than the panp group (p<0.001). patients with a history of htn had significantly higher rates of bleeding recurrence in the panp group (p= 0.001). the absolute risk reduction (arr), relative risk reduction, and number needed to harm of treatment with txa for anterior nasal bleeding were 14.00% (95%ci: 1.11 – 26.89), 17.50% (95%ci: 0.60 37.27), and 7.14 (95%ci: 3.71 -90.43), respectively. 4. discussion the findings of this study indicate that the use of txa for management of epistaxis is associated with faster bleeding cessation, lower rates of re-bleeding, and a shorter length of hospital stay compared to panp. treatment with txa had 17.5% lower risk of rebleeding. number needed to harm of treatment with txa was 7.1, which means that about 7 patients need to be treated with txa in order for one case to have uncontrolled bleeding. local compression is the first step in management of epistaxis with anterior circulation origin (10). the next steps may include the application of a cotton swab soaked in vasoconstrictors, cauterization, and nasal packing. finally, nasal endoscopy may be considered to find underlying pathogenesis, in cases with recurrent epistaxis (5, 10). current clinical guidelines suggest using resorbable packing for patients with bleeding disorders or those receiving antiplatelet or anticoagulation agents (10). packing strategies have shown to lessen the length of hospital stay compared to non-packing ways such as cauterization, embolization, and ligation (11). tranexamic acid is a synthetic analogue of lysine amino acid, which binds to plasminogen and plasmin, thereby inhibiting their ability to bind to residual lysine in fibrin, thus preventing fibrinolysis. it is used in heavy menstrual bleedings, postpartum hemorrhage, bleedings following dental procedures, and hematologic disorders (12). this treatment is readily available, inexpensive, and easy to apply (12, 13). several studies have investigated its effect on controlling epistaxis in patients taking or not taking antiplatelet drugs (9). interestingly, it has been beneficial in nebulized and atomized intranasal forms in patients with difficult-to-control epistaxis (14, 15). literature review on txa efficacy demonstrates its benefits in reducing recurrent bleeding and duration of hospital stay, as well as higher patient satisfaction. similar to our findings, zahed et al. showed that txa is significantly more efficient in bleeding cessation within 10 minutes of application, compared to panp, in patients receiving antiplatelet medications such as aspirin and clopidogrel. moreover, txa reduced re-bleeding within one week of the first episode and the length of hospital stay (7). in a study by saeedi et al., 68% of people treated with txa achieved hemostasis in 5-10 minutes, whereas this measure was 15-20 minutes in patients treated with anterior nasal tampon. they also reported lower re-bleeding rates and hospital length of stay in patients receiving txa, compared to anterior tampon, which are consistent with our findings (16). atabaki et al. made a comparison between phenylephrine and txa in terms of achieving hemostasis after 10 minutes of application in patients with nosebleed, and observed a significant difference between two groups (17). the results of another study by zahed et al., comparing topical use of the injectable form of txa with anp with tetracycline ointment, demonstrated that txa was more efficient in stopping initial bleeding, which led to shorter hospital stay length, but it showed no superiority in reducing bleeding recurrence (9). comparison of the effect of topical application of iv form of txa with topical oxymetazoline spray, a vasoconstrictor medication, revealed the significant advantage of using txa to control bleeding (18). a retrospective study of adult patients with epistaxis who were admitted to a general hospital showed that using txa had considerable results in reducing bleeding. the results of this study specified diabetes and hypertension as strong predictors of re-admission, which is in agreement with our findings (19). a number of studies have investigated the effect of txa on some hematologic disorders (20, 21). the results of a placebo-controlled cross-over trial in patients with hereditary hemorrhagic telangiectasia complaining of epistaxis revealed that the administration of txa significantly reduces the mean duration of epistaxis per month but not the median number of epistaxis episodes per month (20). a similar trial by geisthoff et al. also suggests that the administration of one gram of txa, three times daily for three months can reduce epistaxis score by 54% compared to the placebo in patients with hereditary hemorrhagic telangiectasia (21). among anticoagulant medications, txa was considered an effective management option in a patient with underlying atrial fibrillation, receiving rivaroxaban (a factor x inhibitor used for stroke prophylaxis) who was referred to ed due to epistaxis (22). in contrast to our findings, some studies found little or no benefits in using txa for treating epistaxis. the results of one study, comparing txa gel with placebo, showed no significant differences in time to control bleeding and its recurrence (23). using oral txa for 10 days as adjunct therapy revealed no superiority to placebo regarding re-bleeding this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem 5 archives of academic emergency medicine. 2021; 9(1): e6 table 1: screening performance characteristics of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of mortality and poor outcome variables treatments p value txa (n = 50) panp (n = 50) age (year) 45 55 17 (34.0) 18 (36.0) 55 65 27 (54.0) 25 (50.0) 0.91 ≥ 65 6 (12.0) 7 (14.0) sex male 29 (58.0) 23 (46.0) 0.2 female 21 (42.0) 27 (54.0) diabetes mellitus yes 7 (14.0) 5 (10.0) 0.54 no 43 (86.0) 45 (90.0) hypertension yes 5 (10.0) 13 (26.0) 0.037 no 45 (90.0) 37 (74.0) data are presented as mean ± standard deviation (sd) or number (%). txa: tranexamic acid; panp: phenylephrine/lidocaine soaked anterior nasal packing. table 2: overall performance of rapid emergency medicine score (rems) and rapid acute physiology score (raps) in prediction of in-hospital mortality and poor outcome variables treatments p value txa (n = 50) panp (n = 50) successful bleeding control number (%) 47(94.0) 40 (80.0) 0.037 bleeding cessation time (minutes) < 5 10 (20.0) 1 (2.0) 5 – 10 35 (70.0) 6 (12.0) 0.001 10 15 5 (10.0) 22 (4.0) ≥ 15 0 (0.0) 21 (42.0) re-bleeding in 72 hours n (%) 3 (6.0) 10 (20.0) 0.03 duration of hospital stay (hours) <1 19 (38.0) 3 (6.0) 1 – 2 26 (52.0) 5 (10.0) <0.001 2 -4 3 (6.0) 24 (48.0) >4 2 (4.0) 18 (36.0) data are presented as mean ± standard deviation (sd) or number (%). txa: tranexamic acid; panp: phenylephrine/lidocaine soaked anterior nasal packing and its severity within 10 days of initial epistaxis (24). in the survey of birmingham et al., topical txa was not beneficial for reducing ed length of stay; however, it was associated with a significant reduction in otolaryngologist consults and nasal packing rates in management of acute epistaxis (25). topical use of the iv form of txa seems to provide a better treatment option for anterior epistaxis compared with panp in patients, taking antiplatelet drugs. the advantages of topical txa treatment demonstrated in our study included quick bleeding cessation, and reducing re-bleeding and duration of hospital stay in patients. the technique is also relatively simple and is easy to teach and learn. 5. limitation the main limitation of this study was the small sample size. another limitation was the lack of an objective measurement index for the bleeding cessation in patients with epistaxis; however, we tried to reduce the effect of this limitation by asking for the opinions of an emergency medicine attend for confirming bleeding cessation. 6. conclusion topical txa is an appropriate treatment option for cessation of bleeding, and reducing re-bleeding and duration of hospital stay in patients with epistaxis who take antiplatelet agents. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem k. amini et al. 6 7. declaration 7.1. acknowledgements the authors would like to thank ardabil university of medical sciences, ardabil, iran for financial support, cooperation, and assistance throughout the study. 7.2. author contribution k.a. and a.a.; designed and performed experiments, analyzed data, and wrote the paper. k.a. and s.j.; performed experiments. p.a.; performed bioinformatics analyses. k.a. and a.a.; supervised the research. 7.3. funding/support none. 7.4. conflict of interest the authors declare no conflict of interest. references 1. viehweg tl, roberson jb, hudson j. epistaxis: diagnosis and treatment. journal of oral and maxillofacial surgery. 2006;64(3):511-8. 2. chaaban mr, zhang d, resto v, 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of emergency medicine. 2018;36(7):1242-5. this open-access article distributed under the terms of the creative commons attribution noncommercial 3.0 license (cc by-nc 3.0). downloaded from: http://journals.sbmu.ac.ir/aaem introduction methods results discussion limitation conclusion declaration references